=9) is found due to a common spatial
distribution of the wave functions involved with the first dark exciton and the
first bright exciton, which are characterized primarily by a number of the wave
function nodes. The exciton wave function as well as other properties of smaller
molecules of n = 7 and 8 is, on the contrary, size-sensitive, although and the
peak positions are essentially size-insensitive because of the cancellation of
size-dependence of exciton binding energy and orbital energy. Different size
sensitivity between absorption and fluorescence can thus be explained unless such
cancellation also occurs for fluorescence.
PMID- 28411614
TI - Small static electric field strength promotes aggregation-prone structures in
amyloid-beta(29-42).
AB - The formation of senile plaques in central neural system resulting from the
aggregation of the amyloid beta (Abeta) of 40 and 42 residues is one of the two
hallmarks of Alzheimer's disease. Numerous experiments and computational studies
have shown that the aggregation of Abeta peptides in vitro is very complex and
depends on many factors such as pH, agitation, temperature, and peptide
concentration. The impact of a static electric field (EF) on amyloid peptide
aggregation has been much less studied, although EFs may have some applications
to treat Parkinson's disease symptoms. Here, we study the influence of an EF
strength of 20 mV/nm, present in the human brains, on the conformation of the
Abeta29-42 dimer. Our 7 MUs non-equilibrium atomistic simulations in aqueous
solution show that this field-strength promotes substantially the formation of
beta-hairpins, believed to be a very important intermediate state during
aggregation. This work also suggests that structural biology experiments
conducted under appropriate EF strengths may help reduce the conformational
heterogeneity of Abeta1-40/Abeta1-42 dimers and provide significant insights into
their structures that may be disease-causing.
PMID- 28411615
TI - Water/ice phase transition: The role of zirconium acetate, a compound with ice
shaping properties.
AB - Few compounds feature ice-shaping properties. Zirconium acetate is one of the
very few inorganic compounds reported so far to have ice-shaping properties
similar to that of ice-shaping proteins, encountered in many organisms living at
low temperature. When a zirconium acetate solution is frozen, oriented and
perfectly hexagonal ice crystals can be formed and their growth follows the
temperature gradient. To shed light on the water/ice phase transition while
freezing zirconium acetate solution, we carried out differential scanning
calorimetry measurements. From our results, we estimate how many water molecules
do not freeze because of their interaction with Zr cations. We estimate the
colligative properties of the Zr acetate on the apparent critical temperature. We
further show that the phase transition is unaffected by the nature of the base
which is used to adjust the pH. Our results provide thus new hints on the ice
shaping mechanism of zirconium acetate.
PMID- 28411616
TI - Experimental scaling of plane-Born cross sections and ab initio assignments for
electron-impact excitation and dissociation of XF4 (X = C, Si, and Ge) molecules.
AB - Electron energy loss spectra of carbon tetrafluoride, silicon tetrafluoride, and
germanium tetrafluoride molecules (CF4, SiF4, and GeF4) have been measured for
incident electron energies of 50-360 eV at 1.5 degrees -15.5 degrees and for 30
eV and 30 degrees scattering angle, while sweeping the energy loss over the
range 9.0-20.0 eV. Low-lying valence excited triplet and singlet states are
investigated by quantum chemical ab initio calculations. The Rydberg series
converging to the (lowest) ionisation energy limits of XF4 (X = C, Si, Ge) are
also identified and classified using the systematic behaviour according to the
magnitude of the quantum defects. A generalized oscillator strength analysis is
employed to derive oscillator strength f0 value and the apparent Born integral
cross sections from the corresponding differential cross sections by using the
Vriens formula for the optically allowed transitions. The f0 value is compared
with the optical oscillator strength of the photoabsorption, pseudo-photon
measurements, and theoretical values. The binary-encounter and f-scaled Born
cross sections of the most intense optically allowed transitions have been also
derived from the excitation threshold to the high energy region where the Born
approximation is valid. Potential energy curves were obtained along the XF3 + F
coordinate with two different basis sets to lend support on electron impact
dissociation processes yielding radical formation. We found that in CF4, the
lowest-lying dissociative character is due to intramolecular conversion from
Rydberg 3s to valence character (sigma*(C-F)), whereas in SiF4 and GeF4, an
antibonding behaviour prevails.
PMID- 28411617
TI - Temperature of maximum density and excess properties of short-chain alcohol
aqueous solutions: A simplified model simulation study.
AB - We perform an extensive computational study of binary mixtures of water and short
chain alcohols resorting to two-scale potential models to account for the
singularities of hydrogen bonded liquids. Water molecules are represented by a
well studied core softened potential which is known to qualitatively account for
a large number of water's characteristic anomalies. Along the same lines, alcohol
molecules are idealized by dimers in which the hydroxyl groups interact with each
other and with water with a core softened potential as well. Interactions
involving non-polar groups are all deemed purely repulsive. We find that the
qualitative behavior of excess properties (excess volume, enthalpy, and constant
pressure heat capacity) agrees with that found experimentally for alcohols such
as t-butanol in water. Moreover, we observe that our simple solute under certain
conditions acts as a "structure-maker," in the sense that the temperature of
maximum density of the bulk water model increases as the solute is added, i.e.,
the anomalous behavior of the solvent is enhanced by the solute.
PMID- 28411618
TI - An improved spin-orbit coupling model for use within the effective relativistic
coupling by asymptotic representation (ERCAR) method.
AB - An improved atomic spin-orbit model is presented, which is designed to be used
within the framework of the effective relativistic coupling by asymptotic
representation method. This method is used for the generation of highly accurate
coupled potential energy surfaces (PESs) to represent the fine structure energies
of appropriate systems. The approach is demonstrated using CH3I and its
photodissociation as a typical example. The method is based on a specific
diabatization of electronic spin-space ("spin-free") states with respect to the
asymptote at which a single relativistic atom is separated from a molecular non
relativistic fragment. Thus, the relativistic coupling effects can be treated
entirely within the atomic framework. So far, an effective spin-orbit coupling
operator which only accounts for intra-state coupling within each atomic spin
space state was used. In the present work, this approach is extended to account
for inter-state couplings among different atomic spin-space states as well. It is
shown that this extended approach improves the accuracy of the PESs significantly
for higher excited states and also enhances the accuracy of low energy states. In
particular, it improves the representation of the spin-orbit induced conical
intersection among the 3Q0 and 1Q1 states of CH3I, which is of high relevance for
the nonadiabatic quantum dynamics of the photodissociation.
PMID- 28411619
TI - Statistical properties of fluctuating enzymes with dynamic cooperativity using a
first passage time distribution formalism.
AB - We study the temporal fluctuations in catalytic rates for single enzyme reactions
undergoing slow transitions between two active states. We use a first passage
time distribution formalism to obtain the closed-form analytical expressions of
the mean reaction time and the randomness parameter for reaction schemes where
conformational fluctuations are present between two free enzyme conformers. Our
studies confirm that the sole presence of free enzyme fluctuations yields a non
Michaelis-Menten equation and can lead to dynamic cooperativity. The randomness
parameter, which is a measure of the dynamic disorder in the system, converges to
unity at a high substrate concentration. If slow fluctuations are present between
the enzyme-substrate conformers (off-pathway mechanism), dynamic disorder is
present at a high substrate concentration. Our results confirm that the dynamic
disorder at a high substrate concentration is determined only by the slow
fluctuations between the enzyme-substrate conformers and the randomness parameter
is greater than unity. Slow conformational fluctuations between free enzymes are
responsible for the emergence of dynamic cooperativity in single enzymes. Our
theoretical findings are well supported by comparison with experimental data on
the single enzyme beta-galactosidase.
PMID- 28411620
TI - Ordering of anisotropic nanoparticles in diblock copolymer lamellae: Simulations
with dissipative particle dynamics and a molecular theory.
AB - Local distribution and orientation of anisotropic nanoparticles in microphase
separated symmetric diblock copolymers has been simulated using dissipative
particle dynamics and analyzed with a molecular theory. It has been demonstrated
that nanoparticles are characterized by a non-trivial orientational ordering in
the lamellar phase due to their anisotropic interactions with isotropic monomer
units. In the simulations, the maximum concentration and degree of ordering are
attained for non-selective nanorods near the domain boundary. In this case, the
nanorods have a certain tendency to align parallel to the interface in the
boundary region and perpendicular to it inside the domains. Similar orientation
ordering of nanoparticles located at the lamellar interface is predicted by the
molecular theory which takes into account that the nanoparticles interact with
monomer units via both isotropic and anisotropic potentials. Computer simulations
enable one to study the effects of the nanorod concentration, length, stiffness,
and selectivity of their interactions with the copolymer components on the phase
stability and orientational order of nanoparticles. If the volume fraction of the
nanorods is lower than 0.1, they have no effect on the copolymer transition from
the disordered state into a lamellar microstructure. Increasing nanorod
concentration or nanorod length results in clustering of the nanorods and
eventually leads to a macrophase separation, whereas the copolymer preserves its
lamellar morphology. Segregated nanorods of length close to the width of the
diblock copolymer domains are stacked side by side into smectic layers that fill
the domain space. Thus, spontaneous organization and orientation of nanorods
leads to a spatial modulation of anisotropic composite properties which may be
important for various applications.
PMID- 28411621
TI - On the magnetic circular dichroism of benzene. A density-functional study.
AB - Spectroscopy of magnetic circular dichroism (MCD) provides enhanced information
on molecular structure and a more reliable assignment of spectral bands than
absorption alone. Theoretical modeling can significantly enhance the information
obtained from experimental spectra. In the present study, the time dependent
density functional theory is employed to model the lowest-energy benzene
transitions, in particular to investigate the role of the Rydberg states and
vibrational interference in spectral intensities. The effect of solvent is
explored on model benzene-methane clusters. For the lowest-energy excitation, the
vibrational sub-structure of absorption and MCD spectra is modeled within the
harmonic approximation, providing a very good agreement with the experiment. The
simulations demonstrate that the Rydberg states have a much stronger effect on
the MCD intensities than on the absorption, and a very diffuse basis set must be
used to obtain reliable results. The modeling also indicates that the Rydberg
like states and associated transitions may persist in solutions. Continuum-like
solvent models are thus not suitable for their modeling; solvent-solute clusters
appear to be more appropriate, providing they are large enough.
PMID- 28411622
TI - Modelling oxide formation and growth on platinum.
AB - We present a mathematical model of oxide formation and growth on platinum. The
motivation stems from the necessity to understand platinum dissolution in the
cathode catalyst layer of polymer electrolyte fuel cells. As is known, platinum
oxide formation and reduction are strongly linked to platinum dissolution
processes. However, a consistent model of the oxidation processes on platinum
does not exist. Our oxide growth model links interfacial exchange processes
between platinum and oxygen ions with the transport of oxygen ion vacancies via
diffusion and migration. A parametric analysis is performed to rationalize vital
trends in oxide growth kinetics. The rate determining step of oxide formation and
growth is identified as the extraction of platinum atoms at the metal-oxide
interface. A kinetic effect is observed while adjusting the potential when
growing the oxide layer, and the solution indicates that a structural change
occurs at high potentials, around 1.5 VRHE. The model compares well to
experimental data for various materials from various sources.
PMID- 28411623
TI - Hemoptysis as primary manifestation in three women with choriocarcinoma with
pulmonary metastasis: a case series.
AB - BACKGROUND: Gestational choriocarcinoma is the most common gestational
trophoblastic neoplasia; it is often secondary to hydatidiform mole, as well as
to abortion, ectopic pregnancy, premature delivery, or term delivery.
Approximately 60% of patients with choriocarcinoma develop pulmonary metastases,
but for patients with a respiratory condition, choriocarcinoma with lung
metastasis is a relatively rare lung cancer diagnosis. Three cases of
choriocarcinoma with pulmonary metastasis who had the primary symptom of
hemoptysis are described. CASE PRESENTATION: This case report describes a 35-year
old Chinese woman of Han nationality, a 23-year-old Chinese woman of Han
nationality, and a 46-year-old Chinese woman of Han nationality whose primary
symptom was hemoptysis and different chest imaging manifestations; they were
finally diagnosed as having pulmonary metastatic choriocarcinoma. All patients
had low risk factors, including abortion, hydatidiform mole, and ectopic
pregnancy. Human chorionic gonadotropin played an important role in
choriocarcinoma diagnosis. CONCLUSIONS: Based on the diagnosis and treatment of
the three patients, we suggested that for women with pregnancy history and
hemoptysis (particularly in the presence of risk factors such as abortion,
hydatidiform mole, ectopic pregnancy, and >35-years old), choriocarcinoma may be
the possible diagnosis or at least the main differential diagnosis.
PMID- 28411624
TI - Adverse drug events observed in patients with type 2 diabetes mellitus treated
with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of
published randomized controlled trials.
AB - BACKGROUND: Nowadays, canagliflozin monotherapy, or in combination with other
oral hypoglycemic agents (OHAs), is often administered in patients who are
treated for type 2 diabetes mellitus (T2DM). Therefore, we aimed to
systematically compare the adverse drugs events (AEs) which were associated with
100 mg versus 300 mg canagliflozin respectively, using a large number of
randomized patients with T2DM which were obtained from published trials. METHODS:
Randomized controlled trials (RCTs) comparing 100 mg versus 300 mg canagliflozin
in patients who were treated for T2DM were searched from electronic databases.
AEs reported during a follow up period ranging from 12 to 104 weeks were
considered as the clinical endpoints in this analysis. We calculated odds ratios
(OR) with 95% confidence intervals (CIs) and the analyses were carried out by
RevMan 5 . 3 software. RESULTS: Ten trials involving a total number of 5394
patients (2604 patients who were treated with 100 mg canagliflozin and 2790
patients who were treated with 300 mg canagliflozin) were included. The current
results showed that serious AEs were not significantly higher in patients who
were treated by 300 mg canagliflozin, with OR: 1.01, 95% CI: 0.79-1.29; P = 0.93.
Also, a similar rate of death was observed in patients who were treated by either
100 or 300 mg canagliflozin with OR: 1.13, 95% CI: 0.43-2.94; P = 0.80. Urinary
tract infections, postural dizziness and hypoglycemia were also similarly
manifested, with OR: 0.93, 95% CI: 0.70-1.23; P = 0.61, OR: 1.51, 95% CI: 0.42
5.37; P = 0.53 and OR: 0.96, 95% CI: 0.81-1.13; P = 0.60 respectively. However,
drug discontinuation due to AEs significantly favored 100 mg canagliflozin only
during this unequal follow-up period with OR: 1.35, 95% CI: 1.06-1.72; P = 0.01,
but it was not significantly different when trials with similar follow-up periods
were analyzed. CONCLUSION: 300 mg canagliflozin was not associated with
significantly higher adverse events compared to 100 mg canagliflozin in those
patients who were treated for T2DM. However, because this result was partly
affected by other anti-diabetic medications which were included in the treatment
regimen, further studies based on patients who were treated strictly on
canagliflozin monotherapy should be recommended to completely solve this issue.
PMID- 28411625
TI - Rapid imaging and detection of circulating tumor cells using a wide-field
fluorescence imaging system.
AB - Circulating tumor cells (CTCs) provide potentially accessible in vivo sources of
metastatic cancer cells. As such, considerable focus has been placed on analyzing
the genetics of single-CTCs. Prior to these analyses, however, CTCs must first be
detected within the blood samples of cancer patients. Current methods for
detection of CTCs by fluorescence microscopy require the analysis of hundreds of
images per blood sample, making this a time-consuming process that creates a
bottleneck in CTC analysis. In this study, we therefore developed a wide-field
fluorescence imaging system for rapid CTC detection. For these analyses, CTCs
were first isolated using the microcavity array (MCA), a micro-sized filter for
CTC recovery that separates cells based on differences in cell size and
deformability. Notably, the proposed imaging system enabled rapid (~10 s)
visualization of all stained cells within the 6 mm * 6 mm MCA field via one-shot
imaging. Furthermore, the morphology of the cells in the resulting images
accurately reflected that observed by conventional microscopy. In total,
isolation and detection of CTCs using the MCA combined with our novel wide-field
fluorescence imaging system was achieved within 1 h. Thus, our proposed system
will provide rapid CTC detection system.
PMID- 28411626
TI - Quantitative determination of polysulfide in albumins, plasma proteins and
biological fluid samples using a novel combined assays approach.
AB - Hydrogen sulfide (H2S) signaling involves polysulfide (RSSnSR') formation on
various proteins. However, the current lack of sensitive polysulfide detection
assays poses methodological challenges for understanding sulfane sulfur
homeostasis and signaling. We developed a novel combined assay by modifying
Sulfide Antioxidant Buffer (SAOB) to produce an "Elimination Method of Sulfide
from Polysulfide" (EMSP) treatment solution that liberates sulfide, followed with
methylene blue (MB) sulfide detection assay. The combined EMSP-MB sulfide
detection assay performed on low molecular weight sulfur species showed that
sulfide was produced from trisulfide compounds such as glutathione trisulfide and
diallyl trisulfide, but not from the thiol compounds such as cysteine, cystine
and glutathione. In the case of plasma proteins, this novel combined detection
assay revealed that approximately 14.7, 1.7, 3.9, 3.7 sulfide mol/mol released
from human serum albumin, alpha1-anti-trypsin, alpha1-acid glycoprotein and
ovalbumin, respectively, suggesting that serum albumin is a major pool of
polysulfide in human blood circulation. Taken together with the results of
albumins of different species, the liberated sulfide has a good correlation with
cysteine instead of methionine, indicating the site of incorporation of
polysulfide is cysteine. With this novel sulfide detention assay, approximately
8,000, 120 and 1100 MUM of polysulfide concentrations was quantitated in human
healthy plasma, saliva and tear, respectively. Our promising polysulfide specific
detection assay can be a very important tool because quantitative determination
of polysulfide sheds light on the functional consequence of protein-bound
cysteine polysulfide and expands the research area of reactive oxygen to reactive
polysulfide species.
PMID- 28411627
TI - Combination of electrospray ionization, atmospheric pressure photoionization and
laser desorption ionization Fourier transform ion cyclotronic resonance mass
spectrometry for the investigation of complex mixtures - Application to the
petroleomic analysis of bio-oils.
AB - The comprehensive description of complex mixtures such as bio-oils is required to
understand and improve the different processes involved during biological,
environmental or industrial operation. In this context, we have to consider how
different ionization sources can improve a non-targeted approach. Thus, the
Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been
coupled to electrospray ionization (ESI), laser desorption ionization (LDI) and
atmospheric pressure photoionization (APPI) to characterize an oak pyrolysis bio
oil. Close to 90% of the all 4500 compound formulae has been attributed to CxHyOz
with similar oxygen class compound distribution. Nevertheless, their relative
abundance in respect with their double bound equivalent (DBE) value has evidenced
significant differences depending on the ion source used. ESI has allowed
compounds with low DBE but more oxygen atoms to be ionized. APPI has demonstrated
the efficient ionization of less polar compounds (high DBE values and less oxygen
atoms). The LDI behavior of bio-oils has been considered intermediate in terms of
DBE and oxygen amounts but it has also been demonstrated that a significant part
of the features are specifically detected by this ionization method. Thus, the
complementarity of three different ionization sources has been successfully
demonstrated for the exhaustive characterization by petroleomic approach of a
complex mixture.
PMID- 28411628
TI - Accurate and sensitive determination of molar fractions of 13C-Labeled
intracellular metabolites in cell cultures grown in the presence of isotopically
labeled glucose.
AB - This work describes a methodology based on multiple linear regression and GC-MS
for the determination of molar fractions of isotopically-labeled intracellular
metabolites in cell cultures. Novel aspects of this work are: i) the calculation
of theoretical isotopic distributions of the different isotopologues from an
experimentally measured value of % 13C enrichment of the labeled precursor ii)
the calculation of the contribution of lack of mass resolution of the mass
spectrometer and different fragmentation mechanism such as the loss or gain of
hydrogen atoms in the EI source to measure the purity of the selected cluster for
each metabolite and iii) the validation of the methodology not only by the
analysis of gravimetrically prepared mixtures of isotopologues but also by the
comparison of the obtained molar fractions with experimental values obtained by
GC-Combustion-IRMS based on 13C/12C isotope ratio measurements. The method is
able to measure molar fractions for twenty-eight intracellular metabolites
derived from glucose metabolism in cell cultures grown in the presence of 13C
labeled Glucose. The validation strategies demonstrate a satisfactory accuracy
and precision of the proposed procedure. Also, our results show that the minimum
value of 13C incorporation that can be accurately quantified is significantly
influenced by the calculation of the spectral purity of the measured cluster and
the number of 13C atoms of the labeled precursor. The proposed procedure was able
to accurately quantify gravimetrically prepared mixtures of natural and labeled
glucose molar fractions of 0.07% and mixtures of natural and labeled glycine at
molar fractions down to 0.7%. The method was applied to initial studies of
glucose metabolism of different prostate cancer cell lines.
PMID- 28411629
TI - Fluorescence probe for hypochlorous acid in water and its applications for highly
lysosome-targetable live cell imaging.
AB - Hypochloric acid (HOCl) plays important roles in cell signaling and homeostasis,
such as anti-inflammation and immune regulation, pathogen response and so on.
Accordingly, direct detection of HOCl at the organelle level is important for
investigation of the complex contributions of HOCl to human health. In the
present study, a water soluble lysosome-targeting fluorescent probe Lyso-1
bearing a hydrazone moiety as a HOCl-responsive site and a morpholine unit as a
lysosomal-targeting group has been synthesized and evaluated for its ability to
image lysosomal HOCl. The probe Lyso-1, based on a novel HOCl-promoted hydrazone
oxidation strategy, showed a highly selective fluorescent off/on response to HOCl
with the various reactive oxygen species in water. With increasing amount of ClO-
from 0.5 to 2.5 MUM, a linear correlation between the fluorescence intensity (570
nm) of Lyso-1 and [ClO-] was found, and the regression equation was y = 96.65 +
110.2068[ClO-] with a linear coefficient R of 0.9920. The detection limit is
determined to be 60 nM. Lyso-1 demonstrated a perfect lysosomal targetable
ability, and was successfully applied to image of exogenous, endogenous produced
lysosomal HOCl in live L929 cells. The success of subcellular imaging indicated
that the lysosome-targetable probe Lyso-1 could be used in further applications
for the investigation of biological functions and pathological roles of HClO at
organelle levels.
PMID- 28411630
TI - An immunochromatographic assay for carcinoembryonic antigen on cotton thread
using a composite of carbon nanotubes and gold nanoparticles as reporters.
AB - This paper describes a low-cost, sensitive, visual and rapid
immunochromatographic assay method on cotton thread for carcinoembryonic antigen
(CEA) detection by using novel carbon nanotube/gold nanoparticles (CNT/GNPs)
nanocomposite reporter probe. CEA, a lung cancer protein biomarker, was used as
analyte to demonstrate the principle of the immunochromatographic assay on cotton
thread biosensor. In the presence of target CEA, the decreasing aggregation
amount of CNT/GNPs nanocomposite reporter probes on the test zone induced
directly readout by naked eye. Meanwhile, quantitative detection could be
performed conveniently with a commercial available scanner. The performance with
respect to sensitivity of the method was greatly improved by 2-3 magnitudes
comparing with traditional gold nanoparticles (GNPs) or carbon nanotubes (CNTs)
as reporter probe. Under optimal conditions, the biosensor was capable of
detecting 2.32 ng/mL CEA (S/N >= 3) which is sensitive enough for clinical
diagnosis. These results indicated the novel CNT/GNPs nanocomposite reporter
probe based immunochromatographic assay on cotton thread is particularly suitable
for point-of-care (POC) diagnostics in resource-limited regions.
PMID- 28411631
TI - Escherichia coli adhesive coating as a chiral stationary phase for open tubular
capillary electrochromatography enantioseparation.
AB - Bacteria, the microorganism with intrinsic chirality, have numerous fascinating
chiral phenomena such as various chirality-triggered biological processes and
behaviors. Herein, bacteria were firstly explored as novel chiral stationary
phases in open-tubular capillary electrochromatography (OT-CEC) for
enantioseparation of fluoroquinolone enantiomers and simultaneous separation of
six fluoroquinolone antibiotics. The model strain, i.e. non-pathogenic
Escherichia coli (E. coli) DH5alpha, was adhered onto the inner surface of
positively charged polyethyleneimine (PEI) modified capillaries based on the
bacterial adhesion characteristics and strong electrostatic interaction. The
morphology and thickness of the bacteria adhesive coatings in the capillary were
characterized by field emission scanning electron microscopy (FESEM) and atomic
force microscopy (AFM). Baseline separation of ofloxacin and partial separation
of lomefloxacin enantiomers could be achieved by the E. coli coated columns. The
preparation parameters including the coating time and concentration of bacteria
that affecting the chiral resolution were intensively investigated. The
electrophoretic parameters, including pH, buffer concentration and applied
voltage, were also optimized. The developed method was validated (linearity, LOD,
LOQ, intra-day, inter-day and column-to-column repeatability and recovery) and
successfully utilized for the quantitative analysis of ofloxacin enantiomers in
the ofloxacin tablets. Moreover, only a slight decrease in the separation
efficiency was observed after 90 consecutive runs on the E. coli@capillary. These
results demonstrated that bacteria are promising stationary phases for chiral
separation in CEC.
PMID- 28411632
TI - An ultra-specific and sensitive sandwich ELISA for imatinib using two anti
imatinib antibodies.
AB - The development of an immunoassay for a low-molecular-weight drug first requires
the identification of specific antibodies that do not cross-react with the drug's
metabolites. If two antibodies can simultaneously recognize the entire structure
of the drug, we can then utilize them to establish an ultra-specific sandwich
ELISA, free from interference due to the metabolic products of the drug. This
paper reports an ultra-specific and sensitive sandwich ELISA for determination of
the tyrosine kinase inhibitor imatinib using two anti-imatinib antibodies. The
anti-imatinib antibodies were obtained by two partial structures of imatinib as
haptens (2-(5-amino-2-methylanilino)-4-(3-pyridyl)pyrimidine and 4-{(4-methyl-1
piperazinyl)-methyl}-benzoate). Under optimized conditions, this sandwich ELISA
shows a linear detection range from 64 pg mL-1 to 8 ng mL-1, and a limit of
detection of approximately 64 pg mL-1 for 100-MUL samples. The ELISA is specific
to imatinib and while there was no cross-reactivity with the major metabolite N
desmethyl-imatinib, slight cross-reactivity was found with metabolite pyridine-N
oxide-imatinib. This assay demonstrated significantly lower cross-reactivity with
metabolites than competitive ELISAs. Using this assay, drug levels were easily
measured in rat blood after oral administration of imatinib via a single dose of
30 mg kg-1 or 100 mg kg-1. The levels in rat serum measured by this ELISA were
comparable with those measured by HPLC, and there was a strong correlation
between the values determined by the two methods (y = 0.983x + 0.081, R2 =
0.948). Thus, we have successfully developed the first specific and sensitive
sandwich ELISA for imatinib using two anti-imatinib antibodies. This sandwich
ELISA will be a valuable tool for therapeutic drug monitoring and pharmacokinetic
studies of imatinib.
PMID- 28411633
TI - Proximity hybridization-regulated catalytic DNA hairpin assembly for
electrochemical immunoassay based on in situ DNA template-synthesized Pd
nanoparticles.
AB - Novel hybridization proximity-regulated catalytic DNA hairpin assembly strategy
has been proposed for electrochemical immunoassay based on in situ DNA template
synthesized Pd nanoparticles as signal label. The DNA template-synthesized Pd
nanoparticles were characterized with atomic force microscopic and X-ray
photoelectron spectroscopy. The highly efficient electrocatalysis by DNA template
synthesized Pd nanoparticles for NaBH4 oxidation produced an intense detection
signal. The label-free electrochemical method achieved the detection of
carcinoembryonic antigen (CEA) with a linear range from 10-15 to 10-11 g mL-1 and
a detection limit of 0.43 * 10-15 g mL-1. Through introducing a supersandwich
reaction to increase the DNA length, the electrochemical signal was further
amplified, leading to a detection limit of 0.52 * 10-16 g mL-1. And it rendered
satisfactory analytical performance for the determination of CEA in serum
samples. Furthermore, it exhibited good reproducibility and stability; meanwhile,
it also showed excellent specificity due to the specific recognition of antigen
by antibody. Therefore, the DNA template synthesized Pd nanoparticles based
signal amplification approach has great potential in clinical applications and is
also suitable for quantification of biomarkers at ultralow level.
PMID- 28411634
TI - Encapsulating Proteins in Nanoparticles: Batch by Batch or One by One.
AB - Encapsulation of proteins in nanoparticles (NPs) can greatly improve the
properties of proteins such as their stability against denaturation and
degradation by proteases, and branches out the applications of natural proteins
from their intrinsic localizations and functions in living organisms for
biomedical and industrial applications. We recently developed several methods to
armor proteins in NPs with sizes from nanometers up to >100nm, batch by batch or
one by one, covalently or noncovalently, for a wide range of applications from
biocatalysis to bioimaging and drug delivery. In this chapter, we provide
detailed protocols on these methods. Key steps of specific protocols are
explained with particular examples to help other laboratories to adopt and modify
these methods for their own purposes. The advantages and disadvantages of each
method are summarized, and guidelines for choosing the right method for a given
application, as well as the current challenges and future directions of this
field, are discussed.
PMID- 28411635
TI - Guide to the Preparation of Molecularly Imprinted Polymer Nanoparticles for
Protein Recognition by Solid-Phase Synthesis.
AB - Molecularly imprinted polymers (MIPs) are synthetic antibody mimics possessing
specific cavities designed for a target molecule. Nowadays, molecular imprinting
of proteins still remains a challenge as the generation of selective imprinted
cavities is extremely difficult, due to their flexible structure and the presence
of a multitude of functional sites. To overcome this difficulty, we propose a
solid-phase synthesis strategy to prepare MIPs specific for any protein that can
be immobilized in an oriented way on a solid support. Trypsin and kallikrein were
used as model proteins. The solid-phase support consists of glass beads
functionalized with two affinity ligands of the enzymes, the competitive
inhibitor p-aminobenzamidine to orient the enzymes via their active site, or a
Cu2+chelate to orient via the surface histidine residues of the enzyme.
Thermoresponsive molecularly imprinted polymer nanoparticles (MIP-NPs) are then
synthesized around the immobilized enzyme. The MIP-NPs are released by a simple
temperature change, resulting in protein-free polymers endowed with improved
binding site homogeneity since all binding sites have the same orientation. The
MIP-NPs exhibit apparent dissociation constants between 0.02 and 2nM toward their
target proteins, which is comparable to those of natural antibodies. Moreover,
these water-compatible polymers, targeting different domains of the enzyme, can
also function as protective agents (armor), hence preventing the target proteins
from denaturation by heat or pH.
PMID- 28411636
TI - Armored Urease: Enzyme-Bioconjugated Poly(acrylamide) Hydrogel as a Storage and
Sensing Platform.
AB - Jack bean urease is an important enzyme not only because of its numerous uses in
medical and other fields but also because of its historical significance-the
first enzyme to be crystallized and also the first nickel metalloenzyme. This
enzyme hydrolyzes urea into ammonia and carbon dioxide; however, the stability of
this enzyme at ambient temperature is a bottleneck for its applicability. To
improve urease stability, it was immobilized on different substrates,
particularly on polymeric hydrogels. In this study, the enzyme was coupled
covalently with poly(acrylamide) hydrogel with an yield of 18MUmol/cm3. The
hydrogel served as the nanoarmor and protected the enzyme against denaturation.
The enzyme immobilized on the polymer hydrogel showed no loss in activity for
more than 30 days at ambient temperature, whereas free enzyme lost its activity
within a couple of hours. The Michaelis-Menten constant (Km) for free and
immobilized urease were 0.0256 and 0.2589mM, respectively, on the first day of
the study. The Km of the immobilized enzyme was approximately 10 times higher
than that of the free enzyme. The hydrogel technique was also used to prepare
light diffracting polymerized colloidal crystal array in which urease enzyme was
covalently immobilized. This system was applied for the detection of mercury
(Hg2+) with the lower limit as 1ppb, which is below the maximum contaminant limit
(2ppb) for mercury ions in water. The experimental details of these studies are
presented in this chapter.
PMID- 28411637
TI - Armored Enzyme-Nanohybrids and Their Catalytic Function Under Challenging
Conditions.
AB - Synthesis and characterization of highly stable and functional bienzyme-polymer
triads assembled on layered graphene oxide (GO) are described here. Glucose
oxidase (GOx) and horseradish peroxidase (HRP) were used as model enzymes and
polyacrylic acid (PAA) as model polymer to armor the enzymes. PAA-armored GOx and
HRP covalent conjugates were further protected from denaturation by adsorption
onto GO nanosheets. Structure and morphology of this enzyme-polymer-nanosheet
hybrid biocatalyst (GOx-HRP-PAA/GO) were confirmed by agarose gel
electrophoresis, zeta potential, circular dichroism, and transmission electron
microscopy. The armored biocatalysts retained full enzymatic activities under
challenging conditions of pH (2.5-7.4), warm temperatures (65 degrees C), and
presence of chemical denaturants, 4mM sodium dodecyl sulfate, while GOx/HRP
physical mixtures without the armor had very little activity under the same
conditions. Therefore, this novel combination of two orthogonal approaches,
enzyme conjugation with PAA and subsequent physical adsorption onto GO
nanosheets, resulted in super stable hybrid biocatalysts that function under
harsh conditions. Therefore, this general and powerful approach may be used to
design environmentally friendly, green, biocompatible, and biodegradable
biocatalysts for energy production in biofuel cell or biobattery applications.
PMID- 28411638
TI - Approaches for Conjugating Tailor-Made Polymers to Proteins.
AB - A series of methods are outlined for attaching functional polymers to proteins.
Polymers with good control over structure, functionality, and composition can be
created using reversible addition-fragmentation chain transfer (RAFT)
polymerization. These polymers can be covalently linked to enzymes and proteins
using either the "grafting-to" approach, where a preformed polymer is attached to
the protein surface, or the "grafting-from" approach, where the polymer is grown
from the protein surface. Methods for grafting-to, or attaching the RAFT chain
transfer agent to the protein surface outlined include the commonly used
carbodiimide/activated ester (EDC/NHS) coupling. Methods are also outlined to
graft-from the surface of the protein using RAFT polymerization. Additionally, it
is possible to site specifically introduce a reactive azide group to the protein
surface using enzymatic ligation as a posttranslational modification. This
reactive azide group can be conjugated to an alkyne-containing polymer using
highly efficient click chemistry. These robust protocols can produce protein
polymer conjugates with various architectures and functionalities. Methods are
also outlined for characterization of the resulting bioconjugates.
PMID- 28411639
TI - NanoArmoring of Enzymes by Polymer-Functionalized Iron Oxide Nanoparticles.
AB - Polymer-armored enzymes loaded onto magnetic nanoparticles, as efficient
nanobioreactors with enhanced properties, are described in this chapter. Polymers
are useful macromolecules carrying a large number of surface charges and
repeating units of desired chemical functional groups for linking enzymes onto
them. Magnetic micro/nanoparticles have been widely used as enzyme carriers with
the incorporation of suitable polymer layers. Synthesized iron oxide magnetic
nanoparticles have been used to immobilize a peroxide-catalyzing enzyme-like heme
protein: myoglobin using covalent and noncovalent strategies. The stability,
scalability, and kinetics of the conjugate were studied in detail using
spectroscopic and electrochemical analysis. Compared to the free myoglobin in
solution, myoglobin conjugated to magnetic nanoparticles demonstrated high
catalytic stability and easy recovery from the reaction medium for further use.
Due to the large surface area offered by the magnetic nanoparticles, a large
amount of myoglobin could be loaded with a small amount of magnetic
nanoparticles. Selected examples of polymer-enzyme and polymer-magnetic
nanoparticle-enzyme conjugates developed by us and others are presented in this
chapter, and representative methods for making cost-effective scalable and
reusable enzymatic reactors have been described.
PMID- 28411640
TI - Expression of Cellulolytic Enzyme as a Fusion Protein That Reacts Specifically
With a Polymeric Scaffold.
AB - The formation of higher-order assemblies of multiple proteins or enzymes is a
general mechanism to achieve more sophisticated biological function in biological
systems. For example, cellulosomes are large complexes consisting of multiple
cellulolytic enzymes that rely on the concerted actions of different enzymes
built onto a common protein scaffold to facilitate the breakdown of the polymeric
substrate, cellulose. One strategy for mimicking these highly effective
nanomachines may involve the use of synthetic scaffolds that can react to and
organize multiple engineered enzymes to promote synergistic action between the
enzymes on the scaffold. As an example of the earlier strategy, we describe here
an approach for the expression of cellulolytic enzymes with a serine esterase
tag, and the rapid reaction between the tag and the end-functionalized polymers
to form enzyme-polymer-enzyme multienzyme conjugates. In principle, this general
and versatile supramolecular approach may be used to organize specific
cellulolytic enzymes onto synthetic scaffolds to form multienzyme complexes to
potentially work in synergy for enhanced biological activities. Best reaction
conditions, good activities of the armored cellulolytic enzymes and the design of
optimal protein linker in the fusion protein are discussed in detail. If other
reactive tags are included on the enzyme in future, multiple types of synergistic
enzymes may be positioned at specific sites on a designed polymer scaffold that
mimics the complex structure and enhanced function of natural cellulosomes. This
type of nanoarmoring of multiple enzymes on a nanoscale might also enhance enzyme
stability, when compared to the unprotected enzymes.
PMID- 28411641
TI - Nanoarmoring of Proteins by Conjugation to Block Copolymer Micelles.
AB - The creation of polymer nanoparticles with protein functionality is of great
interest to many applications such as targeted drug or gene delivery, diagnostic
imaging, cancer theranostics, delivery of protein therapeutics, sensing chemical
and biomolecular analytes in complex environments, and design of protective
clothing resembling a second skin. Many approaches to achieving this goal are
being explored in the current literature. In this chapter, we describe a
relatively simple and flexible approach of conjugating the protein to an
amphiphilic block copolymer and creating polymer nanoparticles with protein
functionality by taking advantage of the intrinsic self-assembly behavior of the
amphiphilic block copolymer. The commercially available and biocompatible
polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer is
used as the polymer building block. For demonstrative purposes, bovine serum
albumin was chosen as the protein. We determine the molecular weight of the
protein-polymer conjugate and thereby the degree of conjugation using sodium
dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry measurements. Retention of
protein secondary structure in the conjugate was determined by circular dichroism
spectroscopy, and the biological activity of the protein in the conjugated state
has been evaluated by kinetic assay involving hydrolysis of an organophosphate
compound. Dynamic light scattering and zeta potential measurements were used to
characterize the size and charge of the protein-polymer conjugate micelle.
Precise control of the size of the micelle and surface number density of the
proteins on the micelle surface by coassembling with a second block copolymer
have been demonstrated. These studies document a rational approach to armor the
protein by conjugation with a block copolymer micelle, as a general approach.
PMID- 28411642
TI - Semisynthetic Enzymes by Protein-Peptide Site-Directed Covalent Conjugation:
Methods and Applications.
AB - This chapter describes the rational design and synthesis of semisynthetic lipases
by site-directed incorporation of tailor-made peptides on the lipase-lid site to
improve its activity, specificity, and enantioselectivity in specific
biotransformations. Cysteine was genetically introduced at a particular point of
the oligopeptide lid of the enzyme, and cysteine-containing peptides,
complementary to the amino acid sequence on the lid site of Geobacillus
thermocatenulatus lipase (BTL), were covalently attached on the lid of two
different cysteine-BTL variants based on a fast thiol-disulfide exchange ligation
followed by desulfurization. The BTL variants were initially immobilized on solid
support to introduce the advantages of solid-state chemistry, such as
quantitative transformations, easy purification, and recyclability. In the two
different immobilized variants BTL-A193C and BTL-L230C, the cysteine was then
activated with 2-dipyridyldisulfide to help the disulfide exchange with the
peptide, generating the semisynthetic enzyme in high yield. Excellent results of
improvement of activity and selectivity were obtained. For example, the peptide
BTL conjugate (at position 193) was 40-fold more active than the corresponding
unmodified enzyme for the hydrolysis of per-acetylated thymidine at pH 5, or
fourfold in the desymmetrization of dimethyl-3-phenylglutarate at pH 7. The new
enzyme also exhibited excellent enantioselectivity in the desymmetrization
reaction with enantiomeric excess (ee) of >99% when compared to that of the
unmodified enzyme (ee=78%).
PMID- 28411643
TI - Transgultaminase-Mediated Nanoarmoring of Enzymes by PEGylation.
AB - PEGylation, the covalent attachment of polyethylene glycol to bioactive
molecules, is one of the leading approaches used to prolong pharmacokinetics, to
improve the stability, and to reduce the immunogenicity of therapeutic proteins.
PEG-conjugated products are associated with better therapy outcomes and improved
patient compliance. Widely applied in clinical practice, the technology is mainly
used to modify proteins, peptides, and oligonucleotides but also other drug
delivery systems such as the liposomal one. Undergoing continuous attempts to
optimize therapeutic efficacy and to tune the formation of conjugates, a number
of different PEGylation processes are now available to researchers for protein
conjugation. Although the possibility of obtaining highly homogeneous conjugate
mixtures, preferably formed by a single monoconjugate, from a chemical
conjugation reaction continues to be limited, several enzymatic conjugation
approaches have recently been investigated to address this need. PEGylation
mediated by microbial transglutaminase and its many advantages and modifications
are outlined in detail in the current work permitting interested readers to
perform site-specific protein derivatization to glutamines or lysines.
PMID- 28411644
TI - Enzyme Adsorption on Nanoparticle Surface Probed by Highly Sensitive Second
Harmonic Light Scattering.
AB - Recent developments in second harmonic light scattering technique and the
associated theoretical models have provided a deeper insight of molecular
interactions on micro- and nanoparticle surfaces. This technique is extended to
probe the thermodynamics of protein adsorption on nanoparticle surface which is
crucial for understanding the fate of nanoparticle-based formulations in
biomedical applications. A modified Langmuir adsorption model has been applied to
extract the thermodynamic parameters from the experimental data. The general
applicability of the technique is established by extracting free energy change,
association constant, and binding stoichiometry of adsorption of a moderate size
protein, alcohol dehydrogenase, and a small size protein, insulin, on gold
nanoparticles. The free energy change for the adsorption is found to be of the
order of -55kJ/mol, which indicates that the interaction of proteins with the
nanoparticle surface involves weak forces. On the other hand, the low value of
the free energy change makes the detachment of the protein from the particle
surface easier and guarantees reversibility of the binding process. In addition,
one gets the binding stoichiometry of the proteins with the nanoparticle surface
which opens up the possibility of controlling the payload of the protein- or
peptide-based therapeutics in future biomedical applications.
PMID- 28411645
TI - Polymer-Based Protein Engineering: Synthesis and Characterization of Armored,
High Graft Density Polymer-Protein Conjugates.
AB - Atom transfer radical polymerization (ATRP) from the surface of a protein can
generate remarkably dense polymer shells that serve as armor and rationally tune
protein function. Using straightforward chemistry, it is possible to covalently
couple or display multiple small molecule initiators onto a protein surface. The
chemistry is fine-tuned to be sequence specific (if one desires a single targeted
site) at controlled density. Once the initiator is anchored on the protein
surface, ATRP is used to grow polymers on protein surface, in situ. The technique
is so powerful that a single-protein polymer conjugate molecule can contain more
than 90% polymer coating by weight. If desired, stimuli-responsive polymers can
be "grown" from the initiated sites to prepare enzyme conjugates that respond to
external triggers such as temperature or pH, while still maintaining enzyme
activity and stability. Herein, we focus mainly on the synthesis of chymotrypsin
polymer conjugates. Control of the number of covalently coupled initiator sites
by changing the stoichiometric ratio between enzyme and the initiator during the
synthesis of protein-initiator complexes allowed fine-tuning of the grafting
density. For example, very high grafting density chymotrypsin conjugates were
prepared from protein-initiator complexes to grow the temperature-responsive
polymers, poly(N-isopropylacrylamide), and poly[N,N'
dimethyl(methacryloyloxyethyl) ammonium propane sulfonate]. Controlled growth of
polymers from protein surfaces enables one to predictably manipulate enzyme
kinetics and stability without the need for molecular biology-dependent
mutagenesis.
PMID- 28411646
TI - Nano-Armoring of Enzymes: Rational Design of Polymer-Wrapped Enzymes.
AB - The formulation in which therapeutic proteins are administered plays a key role
in retaining their biological activity. Enzyme wrapping, using synthetic
polymers, is a strategy employed to provide enzymes with lower immunogenicity,
longer circulation times, and better targeting capabilities. Protein-polymer
complexation methods, involving covalent, noncovalent, and electrostatic
interactions, that can provide means to develop formulations for retaining enzyme
stability are discussed in this chapter. Amphiphilic self-cross-linkable polymer
was used to encapsulate capsase-3 enzyme in the nanogel, while inverse emulsion
polymerization method was used to entrap alpha-glucosidase enzyme in the nanogel.
These nanogels were characterized by dynamic light scattering, transmission
electron microscopy, and gel electrophoresis. Upon release of caspase-3 enzyme
from polymeric nanogel, it retained nearly 86% of its original activity.
Similarly, alpha-glucosidase that was encased in the acid cleavable polymeric
nanogel exhibited substantial activity after release under acidic conditions (pH
5, 48h). Nano-armoring of the enzymes were nearly complete and provided high
yields of the encased enzyme.
PMID- 28411647
TI - Nanoarmored Enzymes for Organic Enzymology: Synthesis and Characterization of
Poly(2-Alkyloxazoline)-Enzyme Conjugates.
AB - The properties of enzymes can be altered significantly by modification with
polymers. Numerous different methods are known to obtain such polymer-enzyme
conjugates (PECs). However, there is no universal method to render enzymes into
PECs that are fully soluble in organic solvents. Here, we present a method, which
achieves such high degree of modification of proteins that the majority of
modified enzymes will be soluble in organic solvents. This is achieved by
preparing poly(2-alkyloxazoline)s (POx) with an NH2 end group and coupling this
functional polymer via pyromellitic acid dianhydride onto the amino groups of the
respective protein. The resulting PECs are capable of serving as surfactants for
unmodified proteins, rendering the whole mixture organosoluble. Depending on the
nature of the POx and the molecular weight and the nature of the enzyme, the PECs
are soluble in chloroform or even toluene. Another advantage of this method is
that the poly(2-alkyloxazoline) can be activated with the coupling agent and used
for the enzyme conjugation without further purification. The POx-enzyme
conjugates generated by this modification strategy show modulated catalytic
activity in both, aqueous and organic, systems.
PMID- 28411648
TI - Preparation and Applications of Dendronized Polymer-Enzyme Conjugates.
AB - Dendronized polymer-enzyme conjugates are large, water-soluble macromolecular
structures built from a linear, fully synthetic, dendronized polymer (denpol),
and several copies of enzyme molecules covalently bound to the peripheral
functional groups of the denpol. Since denpol chains comprise repeating units
with regularly branched side chains (dendrons), denpols have a cylindrical shape
and are much thicker than conventional linear polymers. Depending on the dendron
generation and chemical structure, denpols may have a large number of functional
groups on their surface, exposed to the aqueous medium in which they are
dissolved. Enzymes (and also other molecules) can be attached to these functional
groups, for example, via a stable bis-aryl hydrazone (BAH) bond. The dendronized
polymer scaffold might also serve as a nanoarmor and stabilize the delicate
enzymes. One of the denpols which can be used for the preparation of denpol
enzyme conjugates is de-PG2. It has a poly(methacrylate) backbone and consists of
second-generation dendrons with four peripheral amino groups in each repeating
unit. The synthesis of de-PG2 and the preparation of a de-PG2 conjugate carrying
BAH-linked proteinase K (proK), as an example, are described here for
applications in the field of enzyme immobilization on solid surfaces. The
nanoarmored enzyme-polymer conjugate indicated high stability and retention of
enzymatic activity.
PMID- 28411649
TI - Nanoarmoring of Enzymes by Interlocking in Cellulose Fibers With Poly(Acrylic
Acid).
AB - A simple method for interlocking glucose oxidase (GOx) and horseradish peroxidase
(HRP) in cellulose fibers using poly(acrylic acid) (PAA) as an armor around the
enzyme, without any need for activation of the cellulose support, is reported
here. The resulting enzyme paper is an inexpensive, stable, simple, wearable, and
washable biosensor. PAA functions as a multifunctional tether to interlock the
enzyme molecules around the paper fibers so that the enzymes are protected
against thermal/chemical denaturation and not released from the paper when washed
with a detergent. The decreased conformational entropy of the interlocked enzyme
protected by the nanoarmor is likely responsible for increased enzyme stability
to heat and chemical denaturants (retained >=70 percent enzyme activity after
washing with urea or SDS for 30min), and the polymer protects the enzyme against
inactivation by proteases, bacteria, inhibitors, etc. The kinetics of the
interlocked enzyme were similar to that of the enzyme in solution. The Vmax was
6(+/-0.5)mM per minute before washing, then increased slightly to 9(+/-1.4)mM per
minute after washing with water. The Km was 22(+/-6.4mM), which was slightly
higher compared to GOx in solution (25-27mM). Because the surface area of the
paper does not limit the enzyme loading, about 20% of enzyme was successfully
loaded onto the paper (0.2g enzyme per gram of paper), and >=95% of the enzyme
was retained after washing. Interlocking works with other enzymes such as
laccase, where >=60% of the enzyme activity is retained. This novel methodology
provides a low cost, simple, modular approach of achieving high enzyme loadings
in ordinary filter paper, not limited by cellulose surface area, and there has
been no need for complex methods of enzyme engineering or toxic methods of
activation of the solid support to prepare highly active biocatalysts.
PMID- 28411650
TI - Armoring Enzymes by Metal-Organic Frameworks by the Coprecipitation Method.
AB - Enzymatic processes have great potential for applications in industrial
biocatalysis, biosensing, and biomedical engineering. However, poor stability and
difficulty in the reuse of enzymes still create challenges for their use in
catalysis and other applications. In recent years, enzyme-incorporated metal
organic frameworks (enzyme@MOF) have emerged as a new type of armored enzymes and
are thought to be an appealing solution to the above challenges. To date, the
preparation of enzyme-MOF composites can be divided into three categories,
including physical adsorption, covalent conjugation, and coprecipitation. The
coprecipitation method integrates the synthesis of MOFs and encapsulation of
enzymes into one step, allowing common MOFs with regular pore sizes to be used as
carriers for enzyme binding. In this chapter, we present a protocol for the
synthesis of enzyme@MOF composites using the coprecipitation approach with
particular details.
PMID- 28411651
TI - Enzyme Armoring by an Organosilica Layer: Synthesis and Characterization of
Hybrid Organic/Inorganic Nanobiocatalysts.
AB - The availability of highly stable and reusable enzymes is one of the main
challenges in bio-based industrial processes. Enzyme immobilization and
encapsulation represent promising strategies to reach this goal. In this chapter,
the synthetic strategy to produce hybrid organic/inorganic nanobiocatalysts (NBC)
is reported. This strategy is based on the sequential immobilization of an enzyme
on the surface of silica nanoparticles followed by the growth, at the surface of
the nanoparticles, of a shielding layer which serves as an armor to protect the
enzyme against denaturation/degradation. This armor is produced through a
thickness-controlled organosilane poly-condensation onto the nanoparticle surface
around the enzyme to form a protective organosilica layer. The armored
nanobiocatalysts present enhanced catalytic activity and improved stability
against heat, pH, chaotropic agents, proteases, and ultrasound. The method is
versatile in that it can be successfully adapted to a number of different
enzymes.
PMID- 28411652
TI - Strategies for Biophysical Characterization of Protein-Polymer Conjugates.
AB - Protein-polymer conjugates are increasingly viewed as promising avenues to
producing industrial enzymes with high activity capable of withstanding
potentially harsh reaction conditions, or to designing novel therapeutics with
triggered release, controlled masking, or increased resistance to proteolytic
degradation. Common among these applications are the desire to improve the
stability of protein-polymer conjugates to unfolding by exposure to chemicals or
thermal stress. Thus, assays that allow researchers to robustly and easily
characterize protein-polymer conjugates by obtaining thermodynamic parameters for
folding stand to play an important role in the development of improved protein
polymer conjugates. Herein, we describe two techniques, differential scanning
fluorimetry and intrinsic tryptophan fluorescence, used in our laboratories to
obtain thermodynamic parameters of unfolding that allow for direct comparison of
protein-polymer conjugates and the myriad effects of variations in attachment
site, polymer identity, and polymer length. These two experiments, which are
easily amenable to parallelization, are presented as high-throughput replacements
for more traditionally employed circular dichroism experiments and as complements
to functional chemical stability or functional thermal stability experiments.
Each assay is presented in a parallelized format that allows for rapid scaling
and high-throughput analysis of protein-polymer conjugate libraries. Descriptions
of the assays include a discussion of advantages and disadvantages alongside
protocol details and approaches to data analysis.
PMID- 28411653
TI - Preface.
PMID- 28411654
TI - ?
PMID- 28411655
TI - [A new cleansing technique for complex wounds].
AB - Fast, effective and pain-free cleansing is essential in the management of wounds,
in order to favour the formation of the granulation tissue and the filling of the
cavity. Faced with a chronic wound which was not progressing from the
inflammatory phase, caregivers put in place a technique combining negative
pressure therapy and instillations of sodium bicarbonate and oxygenated water.
The initial results are promising, with the patient benefiting from effective and
pain-free cleansing.
PMID- 28411656
TI - ?
PMID- 28411657
TI - [Suicide in France, a situational analysis].
AB - The fall in the number of suicides in France in no way diminishes the urgent need
to act and reinforce the efforts, initiatives and resources to fight against this
human tragedy. Public policies are starting to show results. The action of the
French national suicide watch, associations, health professionals as well as the
perspectives of the French national mental health council should amplify this
movement.
PMID- 28411658
TI - [Improving suicide prevention].
AB - Suicidal thoughts precede a suicide attempt. Knowing the people who are exposed
to such thoughts enables prevention to be improved. The results of a study of the
general population show that one in five French people claim to have already
seriously considered committing suicide. This represents a particularly
concerning public health issue.
PMID- 28411659
TI - [Suicide, a social fact].
AB - Treating suicide as a social fact means disregarding its individual and dramatic
dimensions. Sociologists do not reason on the basis of specific cases but by
studying the variations, in space and time, of suicide rates. Their contribution
relates essentially to a renewed perspective on society: suicide is in fact a
very accurate indicator of the intensity and quality of the bonds which unite or
isolate individuals in a society.
PMID- 28411660
TI - [The clinical manifestation of suicide and its process].
AB - There emerges from the suicidal process much more than a model. When suicide
forces itself on people, it is extremely difficult for them to pull themselves
out of its grip. From the psychopathological crisis to the psychosocial crisis,
the process acts like a psychological trauma which requires adapted care.
PMID- 28411661
TI - [The suicidal crisis in emergency departments].
AB - Professionals working in emergency departments have an important role to play in
assessing and orienting suicidal patients. A patient's suicide risk must be
assessed using the 'Risk-Emergency-Dangerousness' grid. The main objective of the
initial care is to buy time in order to avoid the patient attempting suicide.
Enabling the patient to return home accompanied by a close friend or family
member after their visit to the emergency department must be favoured whenever
possible, by proposing close monitoring.
PMID- 28411662
TI - [Suicide in adolescence].
AB - On average, in one year in France, six in every thirty teenagers have suicidal
thoughts and two attempt suicide. At this age, suicidal behaviour is structured
around psychopathological, developmental and relational dimensions. Talking about
suicide helps to avoid it but educating teenagers in mental health is the best
way of preventing this definitive act.
PMID- 28411663
TI - [Suicide in the elderly].
AB - Suicide in the elderly is a real public health issue and has been the subject of
a national prevention plan. It is very frequently linked to depression. To
prevent people attempting suicide, health professionals must be trained to
recognise and manage a suicidal crisis.
PMID- 28411664
TI - [Work-related suicide].
AB - Work and the working environment can push a person to suicide, notably in the
context of burnout. There are, however, a wide variety of risk factors, suicide
being multifactorial. Identifying protective elements and recognising the warning
signs is essential.
PMID- 28411665
TI - [The nursing care of a suicidal patient].
AB - The management of a suicidal crisis falls within the scope of nursing care. There
is a high rate of recurrence in the months following an attempted suicide. The
nurse monitoring strategy, based on the principle of the 'recontacting' of
patients, has been tested by the team of a post-emergency psychiatric unit of a
university hospital.
PMID- 28411666
TI - [Psychological support for people bereaved by suicide].
AB - For several years, the Deux-Sevres department has been providing psychological
support to people bereaved after the suicide of a loved one. The care provision
is collaborative and coordinated.
PMID- 28411667
TI - ?
PMID- 28411669
TI - [Acting with compassion, designing care together].
AB - Making care and compassion a central concern in the hospital, and more widely
within the community, is essential. This means reflecting on the existential
questioning imposed by illness, on the key role of the nursing function and the
need to act with compassion, as well as on the awareness of our common
vulnerability and the need to support it.
PMID- 28411668
TI - [Realist evaluation for implementation research].
AB - The realist approach to evaluation can be useful faced with the complexity of
health interventions in populations. Implementation is the process by which these
interventions are put into practice. Scientific realism can provide an important
contribution to the development of programme theories through implementation
research, and help to reveal the distal and proximal mechanisms of programmes
aimed at combatting social inequalities in healthcare.
PMID- 28411670
TI - ?
PMID- 28411671
TI - Evidence to Support Screening Women in Their 40s.
AB - A large body of evidence demonstrates a 30% to 50% mortality benefit of screening
mammography for women aged 40 to 49. Because of more rapid cancer growth rates in
younger women, annual screening is more effective than biennial. Studies indicate
that selective screening of women aged 40 to 49 would miss the majority of breast
cancers. If implemented, recent US Preventive Services Task Force breast cancer
screening guidelines, which recommend against routine screening of women in their
40s, could result in thousands of preventable breast cancer deaths per year.
Vigilance is needed to safeguard younger women's access to screening mammography.
PMID- 28411672
TI - Evidence to Support Screening Women Annually.
AB - The American College of Radiology, American Cancer Society, and US Preventive
Services Task Force agree that mammography screening beginning at age 40 saves
more lives than any other strategy. Despite these seemingly concordant summaries
of the benefits of screening mammography, there are persistent debates regarding
when to start and how often women should participate. Costs of screening, both
monetary and personal, comprise the foundation of arguments against screening.
This article specifically explores the evidence related to screening intervals
and attempts to answer the question: should women be screened annually or
biennially?
PMID- 28411673
TI - Breast Cancer Risk Assessment Models and High-Risk Screening.
AB - It is important to recognize that patients at high risk for breast cancer may
benefit by following breast cancer screening paradigms that are more robust than
those recommended for the average-risk population. Assessing individual cancer
risk and using guidelines to determine if a patient is a candidate for genetic
counseling and possibly genetic testing are essential components to comprehensive
breast cancer screening.
PMID- 28411674
TI - Breast Tomosynthesis: Clinical Evidence.
AB - In the last 20 years, there has been rapid evolution of the clinical research on
digital breast tomosynthesis supporting its adoption in clinical breast imaging
practice. Beginning with proof of principle pilot observational studies and
culminating in prospective population-based screening trials and outcome
reporting from clinical practice, there is a wealth of data on the DBT
technology. This article catalogs the scientific and clinical evidence of DBT,
highlighting some of the most important studies that have been reported to date.
PMID- 28411675
TI - Breast Tomosynthesis: Practical Considerations.
AB - Digital breast tomosynthesis (DBT) is rapidly becoming the new standard of care
for breast cancer screening. DBT has improved on the limitations of traditional
digital mammography by increasing cancer detection and decreasing false-positive
examinations. Interpretation of DBT is slightly different than digital
mammography and therefore experience with the technology is paramount to achieve
best performance. Examples of malignancies that should be recalled and benign
findings that are safely called as benign are provided in this article.
Additionally, practical interpretation methods and implementation protocols are
explained.
PMID- 28411676
TI - Synthesized Digital Mammography Imaging.
AB - Synthesized mammography (SM) is a new imaging technique similar to digital
mammography constructed from an acquired digital breast tomosynthesis (DBT)
examination. SM allows for widespread screening using DBT, maintaining the
benefits of DBT while decreasing the radiation of DBT by nearly half. This
article reviews studies evaluating SM, most of which suggest that SM may be
appropriate to use clinically to replace an actual acquired conventional 2
dimensional full-field digital mammogram (FFDM) when using DBT for breast cancer
screening. These results should be interpreted with caution because there are
inherent differences between SM and FFDM image quality and lesion visibility and
larger, more robust studies still need to be performed.
PMID- 28411677
TI - Breast Density Legislation and Clinical Evidence.
AB - Breast density inform legislation is widely accepted in the United States and has
fueled research regarding the clinical significance of dense breast tissue
present on mammography and the value of supplemental screening. This article
reviews the origins and current status of breast density inform laws and
strategies for optimal breast density determination. Clinical evidence that dense
breast tissue is associated with increased breast cancer risk is presented,
together with a review of relative risk compared with other risk factors.
Finally, there is in-depth analysis regarding the rationale, benefits, and risks
of supplemental screening modalities, including ultrasound, tomosynthesis, and
MRI.
PMID- 28411678
TI - Implementation of Whole-Breast Screening Ultrasonography.
AB - Whole-breast screening ultrasonography is being increasingly implemented in
breast imaging centers because numerous studies have shown the benefit of
supplemental screening for women with dense breasts and breast density
notification laws are becoming more widespread. This article reviews the numerous
considerations involved in integrating a screening ultrasonography program into a
busy practice.
PMID- 28411679
TI - Breast MR Imaging in Newly Diagnosed Breast Cancer.
AB - The role of breast MR imaging in preoperative evaluation of disease extent
remains controversial. MR imaging increases detection of mammographically occult
ipsilateral and contralateral disease, but the clinical impact of these
incidental cancers in unknown. There are no randomized trials of recurrence or
mortality as the primary end point. This missing evidence is needed before the
role of extent of disease MR imaging can be outlined. There are specific clinical
scenarios in which breast MR imaging plays a clear role. In most cases, the
decision to obtain MR imaging depends on physician practice style and patient
preference.
PMID- 28411680
TI - MR Imaging: Future Imaging Techniques.
AB - Breast MR imaging is the most sensitive modality for breast cancer detection.
This high sensitivity has led to widespread adoption of this technique,
particularly in screening women at elevated risk for breast cancer. Despite its
high sensitivity, standard breast MR imaging protocols are limited by moderate
specificity and relative higher cost, longer examination time, longer
interpretation time, and lower availability compared with mammography and
ultrasound. As such, new techniques in MR imaging, including abbreviated breast
MR imaging, pharmacokinetic modeling, and diffusion-weighted imaging, are active
areas of research. This article discusses the rationale, current evidence, and
limitations of these new MR imaging techniques.
PMID- 28411681
TI - Breast PET/MR Imaging.
AB - Breast and whole-body PET/MR imaging is being used to detect local and metastatic
disease and is being investigated for potential imaging biomarkers, which may
eventually help personalize treatments and prognoses. This article provides an
overview of breast and whole-body PET/MR exam techniques, summarizes PET and MR
breast imaging for lesion detection, outlines investigations into multi
parametric breast PET/MR, looks at breast PET/MR in the setting of neo-adjuvant
chemotherapy, and reviews the pros and cons of whole-body PET/MR in the setting
of metastatic or suspected metastatic breast cancer.
PMID- 28411682
TI - Update on Preoperative Breast Localization.
AB - The radiologist plays an important role in detection, diagnosis, localization,
pathologic correlation, and follow-up imaging of breast cancer. A successful
breast surgical treatment program relies on the image guidance tools and skills
of the radiologist and surgeon. This article reviews the evolving tools available
for preoperative localization. Non-wire devices provide a safe, efficient,
noninferior alternative to wire localization and can be placed 0 to 30 days
before scheduled surgery. This technology may evolve to other longer-term,
efficient, and cost-effective applications for patients who require neoadjuvant
treatment or who have findings visible only at MR imaging.
PMID- 28411683
TI - Breast Imaging.
PMID- 28411684
TI - In vivo antimalarial activity of synthetic hepcidin against Plasmodium berghei in
mice.
AB - The present study was designed to investigate the antimalarial activity of
synthetic hepcidin and its effect on cytokine secretion in mice infected with
Plasmodium berghei. The mice were infected with P. berghei intravenously and
treated with hepcidin according to 4-day suppression test and Rane's test. The
serum levels of interleukins (IL-1beta, IL-2, IL-6, IL-10, IL-12p70, and IL-17A),
tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the
experimental mice were determined using a cytometric bead array (CBA) kit. The
survival rate of the infected mice was also registered. Additionally, the serum
iron, alanine transaminase (ALT), aspartate transaminase (AST), and total
bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted
direct anti-malarial function in vivo and increased survival rate in a dose
dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2,
and Th17 cytokines, TNF-alpha, and IFN-gamma were inhibited by hepcidin. In
conclusion, our results demonstrated that synthetic hepcidin exerts in vivo
antimalarial activity and possesses anti-inflammatory function, which provides a
basis for future design of new derivatives with ideal anti-malarial activity.
PMID- 28411685
TI - Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol
extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type
2 diabetic rats.
AB - The present study aimed at exploring the therapeutic potential of standard
extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral
administration of BCE at doses of 70, 140, and 280 mg.kg-1, to the normal rats
and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out.
Effects of BCE on blood glucose, body weight, and a range of serum biochemical
parameters were tested, and histopathological observation of pancreatic tissues
was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical
composition of BCE mainly contained mangiferin, isoorientin, vitexin,
isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin,
and nigricanside. BCE caused a significant decrease in the concentrations of
fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride,
low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and
increases in oral glucose tolerance, high density lipoprotein-cholesterol, and
superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic
beta-cells protection effect and stimulation of insulin secretion from the
remaining pancreatic beta-cells could be observed after BCE treatment. The
results indicated that BCE exhibited an excellent hypoglycemic activity, and
alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and
protecting pancreatic beta-cells are the possible mechanisms involved in anti
diabetic activity of BCE.
PMID- 28411686
TI - Mechanism underlying berberine's effects on HSP70/TNFalpha under heat stress:
Correlation with the TATA boxes.
AB - Heat stress can stimulate an increase in body temperature, which is correlated
with increased expression of heat shock protein 70 (HSP70) and tumor necrosis
factor alpha (TNFalpha). The exact mechanism underlying the HSP70 and TNFalpha
induction is unclear. Berberine (BBR) can significantly inhibit the temperature
rise caused by heat stress, but the mechanism responsible for the BBR effect on
HSP70 and TNFalpha signaling has not been investigated. The aim of the present
study was to explore the relationship between the expression of HSP70 and
TNFalpha and the effects of BBR under heat conditions, using in vivo and in vitro
models. The expression levels of HSP70 and TNFalpha were determined using RT-PCR
and Western blotting analyses. The results showed that the levels of HSP70 and
TNFalpha were up-regulated under heat conditions (40 degrees C). HSP70 acted as
a chaperone to maintain TNFalpha homeostasis with rising the temperature, but
knockdown of HSP70 could not down-regulate the level of TNFalpha. Furthermore,
TNFalpha could not influence the expression of HSP70 under normal and heat
conditions. BBR targeted both HSP70 and TNFalpha by suppressing their gene
transcription, thereby decreasing body temperature under heat conditions. In
conclusion, BBR has a potential to be developed as a therapeutic strategy for
suppressing the thermal effects in hot environments.
PMID- 28411687
TI - Oral administration of red ginseng powder fermented with probiotic alleviates the
severity of dextran-sulfate sodium-induced colitis in a mouse model.
AB - Red ginseng is a well-known alternative medicine with anti-inflammatory activity.
It exerts pharmacological effects through the transformation of saponin into
metabolites by intestinal microbiota. Given that intestinal microflora vary among
individuals, the pharmacological effects of red ginseng likely vary among
individuals. In order to produce homogeneously effective red ginseng, we prepared
probiotic-fermented red ginseng and evaluated its activity using a dextran
sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of
intestinal damage indicated that the administration of probiotic-fermented red
ginseng significantly decreased the severity of colitis, compared with the
control and the activity was higher than that induced by oral administration of
ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL
6 and TNF-alpha, inflammatory biomarkers that are increased at the initiation
stage of colitis, were significantly decreased in probiotic-fermented red ginseng
treated groups in comparison to the control group. The levels of inflammatory
cytokines and mRNAs for inflammatory factors in colorectal tissues were also
significantly decreased in probiotic-fermented red ginseng-treated groups.
Collectively, oral administration of probiotic-fermented red ginseng reduced the
severity of colitis in a mouse model, suggesting that it can be used as a
uniformly effective red ginseng product.
PMID- 28411688
TI - Anti-inflammatory and membrane stabilizing properties of methyl jasmonate in
rats.
AB - The present investigation was carried out to evaluate anti-inflammatory and
membrane stabilizing properties of methyl jasmonate (MJ) in experimental rat
models of acute and chronic inflammation. The effects of MJ on acute inflammation
were assessed using carrageenan-induced rat's paw edema model. The granuloma air
pouch model was employed to evaluate the effects of MJ on chronic inflammation
produced by carrageenan in rats. The number of white blood cells (WBC) in pouch
exudates was estimated using light microscopy. The levels of biomarkers of
oxidative stress, such as malondialdehyde (MDA), glutathione (GSH) and activity
of antioxidant enzymes in the exudates, were determined using spectrophotometry.
The membrane stabilizing property of MJ was assessed based on inhibition of
hemolysis of rat red blood cells (RBC) exposed to hypotonic medium. Our results
indicated that MJ (25-100 mg.kg-1, i.p.) produced significant anti-inflammatory
activity in carrageenan-induced paw edema in rats (P < 0.05). MJ reduced the
volume of pouch exudates and the number of WBC in carrageenan-induced
granulomatous inflammation. It also exhibited potent antioxidant and membrane
stabilizing activities. In conclusion, these findings suggest the therapeutic
potentials of methyl jasmonate in disease conditions associated with inflammation
and its anti-inflammatory activity may be related to its antioxidant and membrane
stabilizing activities.
PMID- 28411689
TI - Moutan Cortex and Paeoniae Radix Rubra reverse high-fat-diet-induced metabolic
disorder and restore gut microbiota homeostasis.
AB - The present study was designed to investigate the therapeutic effcts of Moutan
Cortex (CM, root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra (PR,
root of Paeonia veitchii Lynch) on metabolic disorders, focusing on the infuence
of CM and PR on the obesity-related gut microbiota homeostasis. The diet-induced
obese (DIO) mouse model was used to test the therapeutic effects of CM and PR.
The mice were orally administered with CM and PR for 6 weeks, and oral glucose
tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate
the insulin sensitivity of the mice. Sterol-regulatory element binding proteins
(SREBPs) and their target genes were measured by quantitative RT-PCR. High
throughput 16S ribosomal RNA (16S rRNA) gene sequencing technology was used to
determine the composition of gut microbiota, and the metabolites in serum were
analyzed by GC-MS. Our results indicated that CM and PR combination alleviated
obese and insulin resistance in the DIO mice, leading to increased glucose uptake
and gene expression in muscle and liver, and down-regulated SREBPs and their
target genes in liver. Interesting, neither the CM-PR extracts, nor the major
components of CM and PR did not affect SREBPs activity in cultured cells.
Meanwhile, CM and PR significantly modulated the gut microbiota of the high-fat
diet (HFD) treated mice, similar to metformin, and CM-PR reversed the overall
microbiota composition similar to the normal chow diet (NCD) treated mice. In
conclusion, our results provide novel mechanisms of action for the effects of CM
and PR in treating DIO-induced dysregulation of sugar and lipid metabolism.
PMID- 28411690
TI - Two new steroidal saponins isolated from Anemarrhena asphodeloides.
AB - Two new steroidal saponins, named timosaponin P (1) and timosaponin Q (2), were
isolated from the rhizome parts of Anemarrhena asphodeloides Bunge using various
chromatographic methods. Their structures and absolute configurations were
elucidated by a combination of spectroscopic and spectrometric data, including
1D, 2D NMR, HR-ESI-MS and ECD calculations, and this is the first time the
absolute configuration of C-23 of steroidal saponin was confirmed by ECD
calculations.
PMID- 28411691
TI - Flavonoids isolated from Sinopodophylli Fructus and their bioactivities against
human breast cancer cells.
AB - Four prenylated flavonoids compounds 1-4, named sinopodophyllines A-D, and a
flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known
compounds (compounds 5-12 and 14-24) were isolated from the fruits of
Sinopodophyllum hexandrum. The structures of new compounds were elucidated by
extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1
6, 9-11, and 14-17 were tested for their cytotoxicity against human breast-cancer
T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11
showed significant cytotoxicity (IC50 values < 10 MUmol.L-1) against T47D cells.
PMID- 28411692
TI - Quantitation of camellianin A in HepG2 cells using a high performance liquid
chromatography-electrospray ionization tandem mass spectrometric method.
AB - The present study was designed to develop a sensitive and selective high
performance liquid chromatography-tandem mass spectrometric method for the
determination of Camellianin A in HepG2 cells. The extraction of Camellianin A
was achieved using 15% trichloroacetic acid and then separated on a C18 column
interfaced with a triple quadrupole tandem mass spectrometer in multiple reaction
monitoring mode. The mobile phase was consisted of methanol-water (0.1% formic
acid) (55 : 45, V/V). The total run time was 5.0 min. The method was linear in
the concentration range of 0.25-250.0 ng.mL-1. The lower limit of quantification
was 0.25 ng.mL-1. The intra- and inter-day relative standard deviations of entire
concentration range were less than 9.3%. The proposed HPLC-MS/MS method was
successfully applied to detect the intracellular concentration of Camellianin A
in HepG2 cells.
PMID- 28411693
TI - Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) meeting in
July 2016 on chronic venous disease: An important first step.
PMID- 28411694
TI - Predictors of failure and complications of catheter-directed interventions for
pulmonary embolism.
AB - OBJECTIVE: Catheter-directed interventions (CDIs) are increasingly performed for
acute pulmonary embolism (PE) as they are presumed to provide similar therapeutic
benefits to systemic thrombolysis while decreasing the dose of thrombolytic
required and the associated risks. This study aimed to identify factors
associated with CDI failure and to describe anticipated complications. METHODS:
Consecutive patients who underwent CDI for massive or submassive PE between 2009
and 2015 were identified; outcomes and complications were retrospectively
collected. CDI clinical failure was defined as major bleeding, perioperative
stroke or other major adverse procedure-related event, decompensation for
submassive or persistent shock for massive PE, need for surgical
thromboembolectomy, or in-hospital death. Univariate analysis was used to study
the factors associated with CDI failure. RESULTS: There were 102 patients who
received a CDI during the study period (36 standard catheter thrombolysis, 60
ultrasound assisted, 6 other; age, 59.2 +/- 15.9 years; male, 50 [49.0%]; massive
PE, 14 [13.7%]). Five patients (4.9%) had a major contraindication and 15
patients (14.7%) had a minor contraindication to systemic thrombolysis. The mean
alteplase dose was 28.2 +/- 18.8 mg (range, 0-123 mg; three patients had already
received systemic lysis). CDI failure occurred in 15 patients (14.7%; 7 in
massive PE, 8 in submassive PE). Of these patients, seven had major bleeding
events, whereas eight patients decompensated. Ten (9.8%) patients had minor
bleeding events (four access related). Factors associated with CDI failure and
major bleeding included massive PE, age >=70 years, and major contraindication to
thrombolytics. Both failures and bleeding events were independent of lysis dose
and CDI technique. CONCLUSIONS: CDIs for acute PE are not risk-free procedures,
and their use should be individualized on the basis of a risk-benefit ratio.
Particularly for patients with major contraindications to systemic thrombolytics,
CDIs should be used selectively. Lytic dose, within the low-volume range
administered in CDI, and type of CDI seem to have no impact on adverse events.
PMID- 28411695
TI - Invited commentary.
PMID- 28411696
TI - First 10-month results of the Vascular Quality Initiative Varicose Vein Registry.
AB - OBJECTIVE: The Vascular Quality Initiative Varicose Vein Registry (VQI VVR)
represents a new Patient Safety Organization database launched in January 2015 as
a collaborative effort between the American Venous Forum and the Society for
Vascular Surgery. This study was undertaken to identify real-world trends among
treatment choices and outcomes of varicose vein patients. METHODS: Registry data
prospectively captured anatomic, procedural, and outcome data for patients with
C2 or more severe disease undergoing intervention for venous varicosities from
January to November 2015. Univariate descriptive statistics of demographic and
procedural data was performed. Preprocedural and postprocedural comparisons were
performed with t-test or chi2 analysis as appropriate. RESULTS: In total, 2661
veins in 1803 limbs of 1406 patients were treated for varicose vein disease. The
majority of patients were female (71.5%) and white (78.3%). Previous varicose
vein treatment had been undertaken by 31.2%. The most common site of reflux was
the great saphenous vein in 74.4%, with 31% of patients having coexisting deep
venous reflux. The right and left extremities were affected equally. Endovenous
treatment of axial reflux was the preferred treatment in 89.1%, divided largely
between radiofrequency ablation (55.2%) and endovenous laser ablation (33.9%).
Clusters were often treated concomitantly with truncal reflux (n = 488 [76%]).
The majority of cluster treatments were performed in an office-based setting
(78.1%). The majority of clusters were located at the calf (89.7%) and treated
with stab phlebectomy (84.8%). For all patients undergoing intervention for
varicose veins, Venous Clinical Severity Score (VCSS) improved on average 4.68 +/
3.35 (n = 719; P < .001) postoperatively from a mean preoperative VCSS of 9.39
+/- 3.87 to a mean postoperative VCSS of 4.71 +/- 3.83. Improvements were seen in
patient-reported outcomes (PROs) of heaviness, achiness, throbbing, swelling,
itching, appearance, and work impact (total score change, 10.75 +/- 6.94; n =
607; P < .001) from a mean preoperative PRO score of 16.48 +/- 6.23 to a mean
postoperative PRO score of 5.73 +/- 5.80. CONCLUSIONS: The VQI VVR provides
detailed assessment of varicose vein interventions and is useful for monitoring
of changes after treatment. Modern-day varicose vein surgery is characterized by
predominantly endovenous treatment of axial vein reflux, phlebectomy of clusters,
and substantial improvements in both VCSS and PROs.
PMID- 28411698
TI - Invited Commentary.
PMID- 28411697
TI - VeClose trial 12-month outcomes of cyanoacrylate closure versus radiofrequency
ablation for incompetent great saphenous veins.
AB - OBJECTIVE: Endovenous cyanoacrylate closure (CAC) is a new U.S. Food and Drug
Administration-approved therapy for treatment of clinically symptomatic venous
reflux in saphenous veins. The device is indicated for the permanent closure of
lower extremity superficial truncal veins, such as the great saphenous vein
(GSV). Early results from a randomized trial of CAC have been reported
previously. Herein we report 1-year outcomes. METHODS: There were 222 subjects
with symptomatic GSV incompetence randomly assigned to receive either CAC (n =
108) or radiofrequency ablation (RFA; n = 114). After the month 3 visit, subjects
could receive adjunctive therapies aimed at treating visible varicosities and
incompetent tributaries. Vein closure was assessed at day 3 and months 1, 3, 6,
and 12 using duplex ultrasound. Additional study visit assessments included the
Venous Clinical Severity Score; Clinical, Etiology, Anatomy, and Pathophysiology
classification; EuroQol-5 Dimension; and Aberdeen Varicose Vein Questionnaire.
Both time to closure and time to first reopening of the target vein were
evaluated using survival curve analysis. Adverse events were evaluated at each
visit. RESULTS: Of 222 enrolled and randomized subjects, a 12-month follow-up was
obtained for 192 (95 CAC and 97 RFA; total follow-up rate, 192/222 [86.5%]). By
month 1, 100% of CAC subjects and 87% of RFA subjects demonstrated complete
occlusion of the target vein. By month 12, the complete occlusion rate was nearly
identical in both groups (97.2% in the CAC group and 97.0% in the RFA group).
Twelve-month freedom from recanalization was similar in the CAC and RFA groups,
although there was a trend toward greater freedom from recanalization in the CAC
group (P = .08). Symptoms and quality of life improved equally in both groups.
Most adverse events were mild to moderate and not related to the device or
procedure. CONCLUSIONS: In patients with incompetent GSVs, treatment with both
CAC and RFA results in high occlusion rates. Time to complete occlusion was
faster with CAC, and freedom from reopening was higher after CAC. Quality of life
scores improved equally with both therapies.
PMID- 28411699
TI - Outcomes of a single-center experience with classification and treatment of
endothermal heat-induced thrombosis after endovenous ablation.
AB - OBJECTIVE: Endothermal heat-induced thrombosis (EHIT) is a known complication of
endothermal venous ablation procedures. EHIT can lead to deep vein
thrombosis/pulmonary embolism, which cause significant disability and, rarely,
death. Other studies have evaluated risk factors for EHIT. There is an accepted
grading system for EHIT, but there is no consensus on treatment type, duration,
or follow-up. We retrospectively evaluated all cases of EHIT after radiofrequency
ablation or endovenous laser ablation at our institution during a 7-year period,
focusing on classification, treatment, and outcomes of EHIT. METHODS: The
analysis included all patients aged >18 years who underwent radiofrequency
ablation or endovenous laser ablation at our institution, Spectrum Health
Hospital Vein Solutions (Grand Rapids, Mich), between January 1, 2008, and
December 31, 2014. Electronic medical records were queried retrospectively to
identify patients with EHIT during the study interval by International
Classification of Diseases-Ninth Revision code. Demographic data, including age,
gender, comorbidities (eg, history of deep venous thrombosis, hypercoagulable
state, family history of blood clots, etc), body mass index, Clinical, Etiology,
Anatomy, and Pathophysiology (CEAP) classification, and use of preoperative
anticoagulation were collected for each patient in the registry. Each patient had
a required postoperative duplex ultrasound (US) examination within 1 to 2 weeks
of the procedure. Preoperative and postoperative US imaging data and procedure
specific data were also recorded for each patient. EHIT was graded from 1 to 4 by
review of the US studies. Each patient's treatment course was reviewed for type
of anticoagulation, duration of treatment, follow-up imaging, and outcome.
RESULTS: From 2008 to 2014, 4799 ablations were performed at Spectrum Health
Hospital Vein Center, and EHIT was identified in 70 patients. At presentation,
87% of patients were asymptomatic, 10% reported pain, and 2.9% reported swelling.
Patients with EHIT grades 1 or 2 were treated with daily aspirin, and most of
those with grades 3 or 4 were treated with systemic anticoagulation. Repeat US
imaging was performed at 1 to 2 weeks to evaluate progression. Progression was
not seen in any patients treated with systemic anticoagulation (grades 3-4).
Thrombus progression occurred in two patients with grades 1 or 2 EHIT treated
with aspirin. A bleeding complication occurred in one patient. CONCLUSIONS: EHIT
after endovenous ablation occurred in ~1.5% of patients, which is similar to that
reported in the literature. Our review shows that systemic anticoagulation is
effective in the prevention of progression with a low risk of bleeding
complications. Patients with EHIT grades 1 or 2 can be treated with aspirin alone
with a low risk of progression (3%).
PMID- 28411700
TI - Association between antithrombotic therapy and risk of postoperative
complications among patients undergoing endovenous laser ablation.
AB - BACKGROUND: The aim of the study was to evaluate the clinical results and
postoperative complications, especially recanalization or bleeding complications,
in patients with saphenous varicose veins undergoing endovenous laser ablation
(EVLA) while receiving antithrombotic therapy (ATT). METHODS: This retrospective
cohort study included 1136 Japanese patients undergoing EVLA with a 980-nm diode
laser between January 2012 and November 2015 at our institution. The patients
were divided into two groups: ATT users (ATT group) and nonusers (control group).
The ATT group was further divided into two subgroups according to whether the
patients received antiplatelet or anticoagulant therapy. Clinical outcomes and
postoperative complications among these patients were assessed. RESULTS:
Approximately 20% of the patients undergoing surgery for saphenous varicose veins
at our institution received ATT. Of these, 141 (12.4%) received antiplatelet
therapy and 95 (8.4%) received anticoagulant therapy. Successful occlusion of the
full length of the treated vein was achieved in 99.9% of the patients; there were
no severe perioperative complications. Endovenous heat-induced thrombosis
occurred in 2.4% of patients, whereas postoperative complications developed in
1.2% of patients. One patient experienced recanalization (0.08%). There were no
significant between-group differences in the incidence of recanalization and
postoperative complications on univariate analysis. CONCLUSIONS: The clinical
outcomes and postoperative complications of EVLA in the ATT group were equivalent
to those in the control group, indicating that EVLA can be safely performed in
patients receiving ATT.
PMID- 28411701
TI - Lack of symmetry in the major lower limb veins.
AB - BACKGROUND: Contemporary texts frequently present the venous system of the lower
limb as a prime example of bilateral symmetry. However, overt bilateral asymmetry
may be noted. This study was designed to examine and to quantify the level of
symmetry in the lower extremity veins. METHODS: This prospective cohort study
evaluated major anatomic differences between right and left lower extremity veins
in adult patients. Two hundred patients presenting with signs and symptoms of
chronic venous disease (CVD; class 2-6) and venous reflux on duplex ultrasound
were examined. A second group of 25 healthy volunteers without reflux or
obstruction were used as controls. Those with conditions that could potentially
alter vasculature, including vascular malformation, lower extremity trauma, and
previously documented surgery for venous disease or bypass operations, were
excluded. Only overt changes in the main superficial veins (great saphenous and
small saphenous veins) and deep veins (femoral, popliteal, peroneal, and tibial
veins) of the lower extremities were examined for symmetry. The level of small
saphenous vein termination and thigh extension veins were also included. Location
and extent of hypoplasia or aplasia and venous duplication or triplication were
noted for all venous segments. RESULTS: Of the 100 patients (200 limbs) with CVD
class 2-3 (age, 49 years; range, 21-78 years), the extent of asymmetry in the
superficial system, deep system, and combined was 84%, 86%, and 100%,
respectively. Similarly, of the 100 patients (200 limbs) with CVD class 4-6 (age,
56 years; range, 28-84 years), the level of asymmetry in the superficial system,
deep system, and combined was 83%, 84%, and 100%, respectively. Fifty (100 limbs)
healthy volunteers (age, 46 years; range, 18-74 years) also presented similarly
elevated levels of asymmetry compared with both cohorts of differing CVD class
severity (superficial, 78%; deep, 84%; both, 100%). The most common reason for
asymmetry in the great saphenous vein was hypoplasia or aplasia, whereas
duplication was rare. In the small saphenous vein, the level of termination,
thigh extension, and hypoplasia were the more frequent reasons. In the deep
veins, duplication of the femoral and popliteal veins at different locations and
extents was the most common finding for asymmetry. These findings remained
consistent for all subgroups of patients and healthy controls. CONCLUSIONS: A
complete lack of symmetry is consistently seen in CVD patients and healthy
subjects. Asymmetry in the veins of the lower extremities appears to be the norm.
This is true despite examination of only overt changes and exclusion of multiple
veins from the comparison.
PMID- 28411702
TI - Outcomes of iliac vein stents after pregnancy.
AB - OBJECTIVE: Stenting is the first-line treatment for obstructive iliocaval lesions
when intervention is required. The aim of the study was to evaluate iliocaval
stent patency during and after pregnancy in women of reproductive age who became
pregnant after stent placement. METHODS: Female patients of reproductive age (18
45 years old) who underwent iliocaval stenting between May 2007 and March 2014
were identified from a three-center prospectively maintained database. Medical
records were reviewed for demographics, baseline risk factors, operative data,
and clinical follow-up to identify pregnancy and postpartum stent imaging. The
primary end point was stent patency. Standard descriptive statistics were used.
RESULTS: There were 310 women of reproductive age who received iliocaval
stenting; 12 were identified to have had at least one pregnancy after stenting.
The mean age was 28 +/- 5 years. One patient received thrombolysis and stenting
at 14 weeks of pregnancy for deep venous thrombosis (DVT) and May-Thurner
syndrome, three for a previous postpartum DVT (2, 4, and 6 weeks postpartum),
three for DVT before any pregnancy with a history of factor V Leiden, and the
remaining five for unprovoked DVT. All stents were self-expanding with a diameter
range of 14 to 16 mm. Mean time from stenting to pregnancy was 23.3 +/- 28
months. All patients had patent stents during pregnancy and were prescribed
therapeutic low-molecular-weight heparin by their obstetrician. One had
asymptomatic left-sided stent compression 1 year after her second delivery,
treated with balloon dilation. At average follow-up of 61 +/- 56 months, all
patients had patent stents with no ultrasound-identified structural damage or
thrombosis. CONCLUSIONS: Pregnancy does not negatively affect the outcomes of
iliocaval stents after lysis of DVT or May-Thurner syndrome. Iliocaval stenting
is not contraindicated in women of reproductive age, although close clinical and
ultrasound follow-up is warranted during and after pregnancy.
PMID- 28411703
TI - A novel duplex finding of superficial epigastric vein flow reversal to diagnose
iliocaval occlusion.
AB - OBJECTIVE: Although duplex ultrasound (DUS) imaging is the current gold standard
in the diagnosis of femoropopliteal deep venous thrombosis, it is not an optimal
diagnostic modality to diagnose iliocaval occlusion. Screening for iliocaval
occlusion thus remains a challenge for clinicians because of the lack of a
reliable noninvasive technique. This challenge results in most patients
undergoing computed tomography venography or magnetic resonance venography or
invasive venography and intravascular ultrasound imaging. This study reports a
novel, yet simple, reproducible and intuitive, surface DUS finding of physiologic
flow reversal within the superficial epigastric vein (SEV) as a sign of proximal
iliocaval occlusion (ICO). METHODS: This was a retrospective study of 15 patients
who were diagnosed with ICO based on the finding of SEV flow reversal on DUS
imaging. Patient demographics, presenting CEAP C scores, ICO characteristics,
correlation with advanced imaging, and short-term follow-up findings are
reported. RESULTS: Physiologic reversal of the SEV resulted in confirmation of
ICO in all patients who underwent advanced imaging, including computed tomography
venography or traditional venogram along with intravascular ultrasound imaging.
All patients who underwent follow-up DUS scans demonstrated normalization of the
SEV flow after ICO recanalization. CONCLUSIONS: ICO can result in deep venous
thrombosis, post-thrombotic syndrome, and chronic venous insufficiency.
Physiologic flow reversal in SEV is diagnostic of ICO. To the best of our
knowledge, this is the first report of this novel DUS finding.
PMID- 28411704
TI - Lymphoscintigraphic abnormalities in the contralateral lower limbs of patients
with unilateral lymphedema.
AB - OBJECTIVE: The contralateral limbs of patients with unilateral lymphedema in the
lower limbs (LLs) can exhibit abnormal lymphatic circulation, even in the absence
of lymphedema. This idea is based on a number of reports that have studied
isolated cases using lymphoscintigraphy. It is likely that these patients
previously had some form of lymphopathy, and the lymphedema arose after the
action of some external factor. However, there are no studies in the literature
that adequately assess the asymptomatic contralateral limbs of these patients or
address the prevalence and characteristics of the abnormal lymphatic circulation
in these limbs. The aim of this study was to assess the prevalence of abnormal
lymphatic circulation in the asymptomatic contralateral limbs of patients with
unilateral lymphedema of the LL. METHODS: Forty-three patients from the angiology
and vascular surgery ward of the Hospital das Clinicas da Universidade Federal de
Pernambuco with unilateral lymphedema of the LL underwent lymphoscintigraphy. All
patients received a subcutaneous injection of 0.2 mL (74 MBq) of a solution of
dextran 70 labeled with technetium Tc 99m in the first interdigital space of each
foot. Images were obtained on two occasions: 10 minutes and 1 hour after the
injection. The study design was transversal prospective. RESULTS: Among the 43
asymptomatic LLs, 30 (70%) showed abnormal lymphatic circulation. The
lymphoscintigraphic abnormalities found were the following: reduced visualization
of the lymphatic vessels and lymph nodes during 1 hour (83%), collateral
circulation (30%), visualization of the inguinal and pelvic lymph nodes after at
least 1 hour (30%), visualization of the popliteal lymph nodes (20%), dilation
and lymphatic tortuosity (20%), and dermal backflow (10%). CONCLUSIONS: In this
study,70% of the patients with unilateral lymphedema of the LL had some form of
lymphopathy in the contralateral limb during the lymphoscintigraphic examination.
These findings could favor the early treatment of these patients to prevent the
disease from progressing to its most severe stage.
PMID- 28411705
TI - Mechanochemical ablation causes endothelial and medial damage to the vein wall
resulting in deeper penetration of sclerosant compared with sclerotherapy alone
in extrafascial great saphenous vein using an ex vivo model.
AB - BACKGROUND: Nonthermal, tumescentless devices are the next generation of
minimally invasive devices to treat varicose veins. We aimed to investigate the
effects of mechanochemical ablation (MOCA) using ClariVein (Vascular Insights,
Quincy, Mass) on ex vivo great saphenous vein with histology and
immunofluorescent staining. METHODS: Extrafascial great saphenous veins were
harvested during surgery for varicose veins and were treated ex vivo for 10 to 11
minutes with either liquid sclerotherapy or the use of ClariVein, with and
without 3% sodium tetradecyl sulfate. Veins were sectioned and subjected to
hematoxylin and eosin staining and immunofluorescent staining for endothelial and
smooth muscle cell markers (CD31 and alpha-actin) to assess overall damage and
cell death in the vein wall compared with control sections. RESULTS: Histologic
observations confirmed intimal damage from ClariVein, as has been previously
shown; however, medial damage was also evident, which was not observed in control
or liquid sclerotherapy sections. Immunofluorescent staining in the three
sections studied showed a 42% decrease in CD31 staining and 27% mean reduction in
alpha-actin staining up to a depth of 300 MUm with liquid sclerotherapy. This
cytotoxic effect was significantly enhanced by MOCA with a reduction in CD31
staining just above 60% and a 46% mean decrease in alpha-actin staining noted up
to a depth of 300 MUm. Far greater reductions in staining compared with
sclerotherapy were observed up to a depth of 600 MUm. CONCLUSIONS: MOCA using 3%
sodium tetradecyl sulfate increases the penetration of the sclerosant and its
effect into the vein wall and shows superior rates of tissue destruction compared
with liquid sclerotherapy alone. In this model, it appears not solely to damage
the endothelium but also to shear the medial layer, creating small lesions into
which sclerosant can flow and exert its cytotoxic effect.
PMID- 28411706
TI - Report of the Society for Vascular Surgery and the American Venous Forum on the
July 20, 2016 meeting of the Medicare Evidence Development and Coverage Advisory
Committee panel on lower extremity chronic venous disease.
AB - On July 20, 2016, a Medicare Evidence Development and Coverage Advisory Committee
panel assessed the benefits and risks of currently used lower extremity chronic
venous disease (CVD) treatments and their effects on health outcome of the
American adult population. The main purpose of the meeting was to advise the
Centers for Medicare & Medicaid Services on coverage determination for
interventions used for treatment of CVD. A systematic review of the Agency for
Healthcare Research and Quality was presented, followed by lectures of invited
experts and a public hearing of representatives of professional societies and the
industry. After discussing critical issues, the panel voted for key questions.
This report summarizes the presented evidence to support recommendations of the
Society for Vascular Surgery/American Venous Forum coalition and the
presentations on selected discussion topics. These included important venous
disease evidence gaps that have not been sufficiently addressed, venous disease
treatment disparities and how they may affect the health outcomes of Medicare
beneficiaries, and mechanisms that might be supported by the Centers for Medicare
& Medicaid Services to improve the evidence base to optimize the care of patients
with lower extremity CVD.
PMID- 28411707
TI - The evidence supporting treatment of reflux and obstruction in chronic venous
disease.
AB - On July 20, 2016, a Medicare Evidence Development and Coverage Advisory Committee
panel convened to assess the evidence supporting treatment of chronic venous
disease. Several societies addressed the questions posed to the panel. A
multidisciplinary coalition, representing nine societies of venous specialists,
reviewed the literature and presented a consensus opinion regarding the panel
questions. The purpose of this paper is to present our coalition's consensus
review of the literature and recommendations for chronic venous disease.
PMID- 28411708
TI - Life-threatening pulmonary embolism associated with multiple venous aneurysms.
AB - Popliteal venous aneurysms (PVAs) are often reported as a cause of pulmonary
embolism. Previous reports documented the association between a single PVA and
pulmonary embolism. We experienced a rare case with multiple venous saccular and
fusiform aneurysms resulting in a nearly fatal pulmonary embolism. Surgical
ligation is usually considered the first-line treatment for PVAs. In our patient,
however, we selected inferior vena cava filter implantation and anticoagulant
therapy to avoid the phlegmasia cerulea dolens caused by ligation of multiple
aneurysms in both legs. We report a patient with multiple venous aneurysms,
including PVAs, causing a nearly fatal pulmonary embolism.
PMID- 28411709
TI - Chronic refractory venous ulcer exacerbated by a congenital pelvic arteriovenous
malformation successfully treated by transarterial Onyx embolization.
AB - Congenital arteriovenous malformations (AVMs) are an important but often
neglected cause of lower extremity venous hypertension. A case of a chronic
refractory venous stasis ulcer of the lower extremity exacerbated by a pelvic AVM
is presented. Healing of the ulcer was achieved at 2 months without recurrence at
1 year after superselective ethylene vinyl alcohol copolymer (Onyx 34; ev3,
Covidien, Plymouth, Minn) embolization of the AVM nidus. Chronic venous
arterialization should be considered in cases of refractory, nonhealing venous
ulcers. Embolotherapy in addition to standard of care therapy can be a
therapeutic measure. Modification of the Clinical, Etiology, Anatomy, and
Pathophysiology (CEAP) classification to include AVMs as a contributing
pathophysiologic process is suggested.
PMID- 28411710
TI - Invited commentary.
PMID- 28411711
TI - An update on the currently available nonthermal ablative options in the
management of superficial venous disease.
AB - BACKGROUND: Chronic venous insufficiency affects millions of Americans with
symptoms spanning a broad range. Saphenous incompetence resulting in chronic
reflux is at the root of most disease and is amenable to surgical correction.
METHODS: We conducted a systematic review of the literature on nonthermal
ablative techniques using a MEDLINE (Ovid) search from January 2000 to August
2016. Only prospective studies and literature review articles in the English
language were included for final analysis. RESULTS: A total of 358 unique
articles were identified, with a total of 60 articles meeting the stated
inclusion and exclusion criteria. Historically, nonthermal ablative techniques
have not demonstrated clinical results on par with thermal ablative
interventions. However, three newer nonthermal ablative techniques have become
available for use in the United States. Review of the literature demonstrated
significant improvements in nonthermal ablative results, with intermediate-term
data suggesting improved durability. CONCLUSIONS: Advances in nonthermal ablative
techniques have led to a developing role and acceptance in the primary management
of varicose veins and venous insufficiency, even in the setting of challenging
cases.
PMID- 28411712
TI - Treatment options and outcomes for caval thrombectomy and resection for renal
cell carcinoma.
AB - OBJECTIVE: Advanced renal cell carcinoma (RCC) has a significant predisposition
to vascular invasion. Tumor vascular invasion and thrombus are found in the renal
vein and the inferior vena cava (IVC) in up to 10% to 25% of patients. This study
reviewed the current status of radical nephrectomy with IVC thrombectomy for
advanced RCC. METHODS: A two-level search strategy of the literature (MEDLINE,
PubMed, The Cochrane Library, and Google Scholar) for relevant articles listed
between January 2000 and December 2015 was performed. The review was confined to
patients with primary RCC associated with vascular invasion. RESULTS: Untreated
RCC with intravascular thrombus has a median survival of 5 months. Surgical
exposure and intervention are tailored to the level of tumor thrombus. The 30-day
mortality for radical nephrectomy with IVC thrombectomy is low (1.5%-10%), and
the complication rates have been reported to be 18%, 20%, 26%, and 47% for IVC
tumor thrombus level I, II, III, and IV disease, respectively. Disease-specific
survival ranges from 40% to 60% at 5 years after nephrectomy and removal of the
intravascular tumor. CONCLUSIONS: Radical nephrectomy with IVC thrombectomy is an
effective cancer control operation that can be safely performed with acceptable
mortality and morbidity. Preoperative imaging coupled with perioperative surgical
management of the IVC is critical to procedural success and patient outcomes.
PMID- 28411713
TI - Cosmetic sclerotherapy.
AB - Telangiectasias and spider veins are considered a common cosmetic concern for
both women and men. Sclerotherapy is a frequently used, low-risk, and highly
successful method to treat these venous problems. This article reviews the
pathophysiology and diagnosis of telangiectasias and reticular veins as well as
the currently available agents and techniques of sclerotherapy. The possible
complications and adverse outcomes of sclerotherapy are described. Standard care
and follow-up for patients after the procedure are outlined. Also included are
tips and tricks found to be valuable in a busy vein practice.
PMID- 28411714
TI - Evaluating the venous experience in vascular surgery training.
AB - OBJECTIVE: There is an increasing recognition and treatment of venous disease in
the United States; results of the Society for Vascular Surgery 2014 membership
survey showed that venous disease represents 18.8% of a vascular surgeon's
current practice. Despite this, there are no operative objectives or case
requirements specific to venous disease for vascular surgery trainees. The
objective of this study was to examine the current venous surgical training
experience of graduating vascular surgery trainees. METHODS: Following
Institutional Review Board waiver and Association of Program Directors in
Vascular Surgery and Residency Review Committee approval, results of the 2014
Association of Program Directors in Vascular Surgery Educational Needs Assessment
Survey pertinent to venous training as well as the Vascular Surgery In-Training
Examination (VSITE) venous scores were summarized. Using the Residency Review
Committee case log database, venous case logs of 0/5 resident and 5/2 fellow
vascular surgery graduates from 2012 to 2015 differentiated by Current Procedural
Technology code were summarized. Venous case logs of 0/5 vascular surgery
residents were compared with those of 5/2 fellows using a Student t-test, with
results considered statistically significant at P < .05. RESULTS: Of the recent
vascular surgery graduates, 15% thought they encountered training gaps in venous
procedures; 54% thought this was due to a gap in vascular surgery training,
whereas 43% thought this was due to evolution in technology. Venous VSITE scores
were similar between 0/5 residents and 5/2 fellows (69% vs 76% correct answers,
respectively), as were overall VSITE scores (70% vs 74% correct answers,
respectively). The 0/5 residents completed between 11 and 264 cases and 5/2
fellows completed between 1 and 188 cases during their training. The 0/5
residents' venous cases were 8.1% of overall cases and the 5/2 fellows' cases
were 4.3% of overall cases during their training. CONCLUSIONS: Current vascular
surgery trainee experience is highly variable and not consistent with future
vascular surgery clinical practice. Vascular surgery trainee fund of knowledge
does not appear affected. Program directors should consider developing a better
defined venous curriculum that includes venous case minimums in defined
categories.
PMID- 28411715
TI - Proposal for a national coverage determination for the treatment of varicose
veins and venous disease due to disparate Centers for Medicare and Medicaid
Services local coverage determination policies.
AB - Varicose veins and chronic venous disease are common problems in the United
States. Persons with these conditions often have an adversely affected quality of
life. There are a number of proven interventions to treat varicose veins and to
improve patients' life quality, but these interventions are often restricted by
the Centers for Medicare and Medicaid Services and private third-party payers.
The Centers for Medicare and Medicaid Services have private contractors that
administer Medicare policies in 10 jurisdictions across the United States. There
is no national policy or coverage for the treatment of varicose veins; rather,
there are multiple, disparate regional policies written by the contractors that
cover the same Medicare beneficiary population. These disparate policies are not
evidence based and provide unfair coverage of the same disease to the Medicare
population, depending on where they live. Our proposal is for a national coverage
determination policy for the treatment of varicose veins.
PMID- 28411716
TI - Pathophysiology of varicose veins.
AB - BACKGROUND: Varicose veins, a common problem with effects on quality of life,
account for a significant cost burden on the health care system. Despite their
prevalence, the pathophysiologic mechanism of varicose veins remains incompletely
understood. The fundamental issue is whether venous hypertension and valvular
incompetence precede and influence the development of vein wall changes or
whether the reverse is true. METHODS: We have reviewed the English-language
literature to provide the most current understanding of the hemodynamic and
cellular and molecular processes that underlie the development of varicose veins.
RESULTS: Data at this time remain inconclusive, with compelling arguments to be
made for both sides. It is clear that valvular incompetence and hemodynamic
factors play a significant role, despite heterogeneity in study findings and lack
of clear data for a specific pattern of valvular incompetence as an inciting
factor. Numerous factors influence the development of varices on the cellular
level, including hypoxia, dysregulated apoptosis, and alterations in the
extracellular matrix. CONCLUSIONS: Based on currently available evidence,
varicose veins are a complex disease with multifactorial pathogenesis; it is as
yet not possible to state conclusively what inciting factor is responsible for
the development of varicose veins, and their development may result from
imbalance of any number of several factors.
PMID- 28411717
TI - Utilizing registries to meet Medicare reimbursement requirements.
PMID- 28411718
TI - Regarding "Validation of the novel venous drainage index with stepwise increases
in thigh compression pressure in the quantification of venous obstruction".
PMID- 28411719
TI - Reply.
PMID- 28411720
TI - Inter- and intra- observer reliability of risk assessment of repetitive work
without an explicit method.
AB - A common way to conduct practical risk assessments is to observe a job and report
the observed long term risks for musculoskeletal disorders. The aim of this study
was to evaluate the inter- and intra-observer reliability of ergonomists' risk
assessments without the support of an explicit risk assessment method. Twenty-one
experienced ergonomists assessed the risk level (low, moderate, high risk) of
eight upper body regions, as well as the global risk of 10 video recorded work
tasks. Intra-observer reliability was assessed by having nine of the ergonomists
repeat the procedure at least three weeks after the first assessment. The
ergonomists made their risk assessment based on his/her experience and knowledge.
The statistical parameters of reliability included agreement in %, kappa,
linearly weighted kappa, intraclass correlation and Kendall's coefficient of
concordance. The average inter-observer agreement of the global risk was 53% and
the corresponding weighted kappa (Kw) was 0.32, indicating fair reliability. The
intra-observer agreement was 61% and 0.41 (Kw). This study indicates that risk
assessments of the upper body, without the use of an explicit observational
method, have non-acceptable reliability. It is therefore recommended to use
systematic risk assessment methods to a higher degree.
PMID- 28411721
TI - Ergonomic analysis of construction worker's body postures using wearable mobile
sensors.
AB - Construction jobs are more labor-intensive compared to other industries. As such,
construction workers are often required to exceed their natural physical
capability to cope with the increasing complexity and challenges in this
industry. Over long periods of time, this sustained physical labor causes bodily
injuries to the workers which in turn, conveys huge losses to the industry in
terms of money, time, and productivity. Various safety and health organizations
have established rules and regulations that limit the amount and intensity of
workers' physical movements to mitigate work-related bodily injuries. A precursor
to enforcing and implementing such regulations and improving the ergonomics
conditions on the jobsite is to identify physical risks associated with a
particular task. Manually assessing a field activity to identify the ergonomic
risks is not trivial and often requires extra effort which may render it to be
challenging if not impossible. In this paper, a low-cost ubiquitous approach is
presented and validated which deploys built-in smartphone sensors to
unobtrusively monitor workers' bodily postures and autonomously identify
potential work-related ergonomic risks. Results indicates that measurements of
trunk and shoulder flexions of a worker by smartphone sensory data are very close
to corresponding measurements by observation. The proposed method is applicable
for workers in various occupations who are exposed to WMSDs due to awkward
postures. Examples include, but are not limited to industry laborers, carpenters,
welders, farmers, health assistants, teachers, and office workers.
PMID- 28411722
TI - Kinematic and ergonomic assessment of laparoendoscopic single-site surgical
instruments during simulator training tasks.
AB - While laparoendoscopic single-site surgery (LESS) appears to be feasible and
safe, instrument triangulation, tissue handling, and other bimanual tasks are
difficult even for experienced surgeons. Novel technologies emerged to overcome
LESS' procedural and ergonomic difficulties of "tunnel vision" and "instrument
clashing." Surgeon kinematics, self-reported workload and upper body discomfort
were used to compare straight, bent and two articulating instruments while
performing two basic surgical tasks in a LESS simulator. All instruments resulted
in bilateral elevation and rotation of the shoulders, excessive forearm motion
and flexion and ulnar deviation of wrists. Surgeons' adopted non-neutral upper
extremity postures and performed excessive joint excursions to compensate for
reduced freedom of movement at the single insertion site and to operate the
instrument mechanisms. LESS' cosmetic benefits continue to impact laparoscopic
surgery and by enabling performance through improved instruments, ergonomic
improvement for LESS can reduce negative impact on surgeon well-being and patient
safety.
PMID- 28411723
TI - Fatigue of Chinese railway employees and its influential factors: Structural
equation modelling.
AB - Fatigue is an identifiable and preventable cause of accidents in transport
operations. Regarding the railway sector, incident logs and simulation studies
show that employee fatigue leads to lack of alertness, impaired performance, and
occurrence of incidents. China has one of the largest rail systems in the world,
and Chinese railway employees work under high fatigue risks; therefore, it is
important to assess their fatigue level and find the major factors leading to
fatigue. We designed a questionnaire that uses Multidimensional Fatigue
Instrument (MFI-20), NASA-TLX and subjective rating of work overtime feelings to
assess employee fatigue. The contribution of each influential factor of fatigue
was analysed using structural equation modelling. In total, 297 employees from
the rail maintenance department and 227 employees from the locomotive department
returned valid responses. The average scores and standard deviations for the five
subscales of MFI-20, namely General Fatigue, Physical Fatigue, Reduced Activity,
Reduced Motivation, and Mental Fatigue, were 2.9 (0.8), 2.8 (0.8), 2.5 (0.8), 2.5
(0.7), and 2.4 (0.8) among the rail maintenance employees and 3.5 (0.8), 3.5
(0.7), 3.3 (0.7), 3.0 (0.6), and 3.1 (0.7), respectively, among the locomotive
employees. The fatigue of the locomotive employees was influenced by feelings
related to working overtime (standardized r = 0.22) and workload (standardized r
= 0.27). The work overtime control and physical working environment significantly
influenced subjective feelings (standardized r = -0.25 and 0.47, respectively),
while improper work/rest rhythms and an adverse physical working environment
significantly increased the workload (standardized r = 0.48 and 0.33,
respectively).
PMID- 28411724
TI - Thermal comfort of seats as visualized by infrared thermography.
AB - Published studies that deal with the question of how the temperature of chair
seats influences human activities are few, but the studies considering such a
factor, a function of the type of material, could contribute to improvements in
the design of chairs. This study evaluates seat temperatures of 8 types of chairs
made of different materials. The parts of the furniture that people come into
contact with, and the thermal response of the material to heating and cooling
have been evaluated. Infrared thermography was used for this, as it is a non
contact technique that does not present any type of risk in the measurement of
temperatures. Seats made of synthetic leather (leatherette), wood and polyester
fabric were found to have the highest temperatures, and the plywood seat showed
the lowest. The study has also revealed that thermography can contribute to
studies of thermal comfort of chair seats in addition to determining the most
suitable material.
PMID- 28411725
TI - Effects of heat stress on risk perceptions and risk taking.
AB - Exposure to extreme heat at work is a serious occupational hazard, as exposure
can result in heat-related illnesses, and it has been linked to increased risk of
accidents and injuries. The current study aimed to examine whether heat exposure
is related to changes in individuals' psychological process of risk evaluation,
and whether acclimatization can mitigate the effect of heat exposure. A study
with quasi-experiment research design was used to compare participants' risk
perceptions and risk-taking behaviors at baseline, initial exposure to heat, and
exposure after acclimatization across male participants who were exposed to heat
(N = 6), and males (N = 5) and females (N = 6) who were in the control group who
were exposed to ambient temperature. Results show that participants perceived the
same risky behaviors to be less risky (p = 0.003) and demonstrated increased risk
taking behaviors (p = 0.001) after initial heat exposure. While their risk
perceptions returned to baseline level after acclimatization, their risk-taking
behaviors remained heightened (p = 0.031). Participants who were not exposed to
heat showed no significant fluctuation in their risk perceptions and risk-taking.
Our findings support that risk-related processes may explain the effects of heat
exposure on increased accidents and injuries beyond its direct impact on heat
related illnesses.
PMID- 28411726
TI - A wellness platform for stereoscopic 3D video systems using EEG-based visual
discomfort evaluation technology.
AB - Recent advances in three-dimensional (3D) video technology have extended the
range of our experience while providing various 3D applications to our everyday
life. Nevertheless, the so-called visual discomfort (VD) problem inevitably
degrades the quality of experience in stereoscopic 3D (S3D) displays. Meanwhile,
electroencephalography (EEG) has been regarded as one of the most promising brain
imaging modalities in the field of cognitive neuroscience. In an effort to
facilitate comfort with S3D displays, we propose a new wellness platform using
EEG. We first reveal features in EEG signals that are applicable to practical S3D
video systems as an index for VD perception. We then develop a framework that can
automatically determine severe perception of VD based on the EEG features during
S3D video viewing by capitalizing on machine-learning-based braincomputer
interface technology. The proposed platform can cooperate with advanced S3D video
systems whose stereo baseline is adjustable. Thus, the optimal S3D content can be
reconstructed according to a viewer's sensation of VD. Applications of the
proposed platform to various S3D industries are suggested, and further technical
challenges are discussed for follow-up research.
PMID- 28411727
TI - Evaluation of the Indonesian National Standard for elementary school furniture
based on children's anthropometry.
AB - In Indonesia, National Standardization Agency of Indonesia issued the Indonesian
National Standard SNI 12-1015-1989 and SNI 12-1016-1989 to define the type of
furniture dimensions that should be used by children in the elementary school
level. This study aims to examine whether the current national standards for
elementary school furniture dimensions issued by National Standardization Agency
of Indonesia match the up-to-date Indonesian children's anthropometry. Two types
of school furniture, small type (Type I, for grade 1-3) and large type (Type II,
for grade 4-6), were evaluated in terms of seat height, seat depth, seat width
and backrest height of a chair as well as the height and underneath height of a
desk. 1146 students aged between 6 and 12 years old participated in the study.
Seven anthropometric measurements were taken including stature, sitting shoulder
height, sitting elbow height, popliteal height, buttock-popliteal length, knee
height and hip breadth. Based on the standard school furniture dimensions and
students' body dimensions, numbers of matches and mismatches between them were
computed. Results indicated a substantial degree of mismatch between children's
anthropometry and the standard dimensions of school furniture. The standard seat
height was not appropriate for students among different grades with the mismatch
percentage ranging from 63.4% to 96.7% for Type I and 72.7% to 99.0% for Type II.
For desk height, the standard dimensions were not appropriate for students among
different grades with the mismatch percentage ranging from 32.3% to 88.9% for
Type I and 67.7% to 99.0% for Type II. Apparently, the current standards are out
of date and need to be updated. Four different sizes of school furniture were
hence proposed to accommodate the variation in students' anthropometry from Grade
1 to Grade 6. The proposed standard dimensions (PrS) of school furniture cover a
slightly broader range of age and present a higher cumulative fit than the
current standard dimensions (CrS). In addition, a better strategy for sizing can
be also developed to fit chairs and desks to a larger number of students.
PMID- 28411728
TI - Improvements in musculoskeletal health and computing behaviors: Effects of a
macroergonomics office workplace and training intervention.
AB - Computer use and its association with musculoskeletal and visual symptoms is an
escalating concern. Organizations are shifting to a more proactive injury
prevention perspective. Accordingly, a macroergonomics intervention consisting of
flexible workplace design and office ergonomics training was designed to examine
the effects on worker's computing behaviors, postures, and musculoskeletal
discomfort, and their relationship to psychosocial factors. Participants were
assigned to either group: 1) no-intervention control 2) flexible Workplace-only
(WP-only), and 3) flexible Workplace + Training (WP+T). Observational findings
indicate both intervention groups experienced positive, significant changes in
improved workstation arrangements and computing postures, with the WP+T
intervention group exhibiting a higher, significant change of behavioral
translation. Also, significant, positive relationships between observed postures
and musculoskeletal discomfort/pain were found. The intervention effect was
stronger when management was responsive to workers' ergonomics needs. This study
suggests that a macroergonomics intervention can produce beneficial effects for
office and computer workers and organizations.
PMID- 28411729
TI - Design with limited anthropometric data: A method of interpreting sums of
percentiles in anthropometric design.
AB - Occasionally practitioners must work with single dimensions defined as
combinations (sums or differences) of percentile values, but lack information
(e.g. variances) to estimate the accommodation achieved. This paper describes
methods to predict accommodation proportions for such combinations of percentile
values, e.g. two 90th percentile values. Kreifeldt and Nah z-score multipliers
were used to estimate the proportions accommodated by combinations of percentile
values of 2-15 variables; two simplified versions required less information about
variance and/or correlation. The estimates were compared to actual observed
proportions; for combinations of 2-15 percentile values the average absolute
differences ranged between 0.5 and 1.5 percentage points. The multipliers were
also used to estimate adjusted percentile values, that, when combined, estimate a
desired proportion of the combined measurements. For combinations of two and
three adjusted variables, the average absolute difference between predicted and
observed proportions ranged between 0.5 and 3.0 percentage points.
PMID- 28411730
TI - Thermal sensation, rate of temperature change, and the heat dissipation design
for tablet computers.
AB - Past research has shown that the rate of change of skin surface temperature can
affect thermal sensation. This study investigated users' thermal responses to a
tablet heating surface with different heat pads and different temperature change
rates. The test conditions included: A. keeping the surface at a constant 42
degrees C, B. increasing the surface temperature from 38 degrees C to 42
degrees C at a rate of 0.02 degrees C/s in progressive intervals, C. increasing
the temperature at 0.15 degrees C/s in progressive intervals, and D. Heating two
left and right side pads alternately from 38 degrees C to 42 degrees C at 0.15
degrees C/s in progressive intervals. Overall results showed the lowest
temperature change rate of 0.02 degrees C/s was most preferred in terms of
thermal comfort. The findings suggest a potential to improve user thermal
experience by dissipating tablet computer heat at a lower temperature change
rate, or by alternating the dissipation areas.
PMID- 28411731
TI - Take-over again: Investigating multimodal and directional TORs to get the driver
back into the loop.
AB - When a highly automated car reaches its operational limits, it needs to provide a
take-over request (TOR) in order for the driver to resume control. The aim of
this simulator-based study was to investigate the effects of TOR modality and
left/right directionality on drivers' steering behaviour when facing a head-on
collision without having received specific instructions regarding the directional
nature of the TORs. Twenty-four participants drove three sessions in a highly
automated car, each session with a different TOR modality (auditory,
vibrotactile, and auditory-vibrotactile). Six TORs were provided per session,
warning the participants about a stationary vehicle that had to be avoided by
changing lane left or right. Two TORs were issued from the left, two from the
right, and two from both the left and the right (i.e., nondirectional). The
auditory stimuli were presented via speakers in the simulator (left, right, or
both), and the vibrotactile stimuli via a tactile seat (with tactors activated at
the left side, right side, or both). The results showed that the multimodal TORs
yielded statistically significantly faster steer-touch times than the unimodal
vibrotactile TOR, while no statistically significant differences were observed
for brake times and lane change times. The unimodal auditory TOR yielded
relatively low self-reported usefulness and satisfaction ratings. Almost all
drivers overtook the stationary vehicle on the left regardless of the
directionality of the TOR, and a post-experiment questionnaire revealed that most
participants had not realized that some of the TORs were directional. We conclude
that between the three TOR modalities tested, the multimodal approach is
preferred. Moreover, our results show that directional auditory and vibrotactile
stimuli do not evoke a directional response in uninstructed drivers. More salient
and semantically congruent cues, as well as explicit instructions, may be needed
to guide a driver into a specific direction during a take-over scenario.
PMID- 28411732
TI - Design and validation of an aircraft seat comfort scale using item response
theory.
AB - This article aims to evaluate the psychometric properties of a scale that
measures aircraft seat comfort. Factor analysis was used to study data variances.
Psychometric quality was checked by using Item Response Theory. The sample
consisted of 1500 passengers who completed a questionnaire at a Brazilian
airport. Full information factor analysis showed the presence of one dominant
factor explaining 34% of data variance. The scale generated covered all levels of
comfort data, from 'no comfort' to 'maximum comfort'. The results show that the
passengers consider there is comfort, but this is very minimal when these
passengers have to perform their desired activities. It tends to increase when
aspects of the aircraft seating are improved and positive emotions are elicited.
Comfort peaks when pleasure is experienced and passenger expectations are
exceeded (maximum comfort). This outcome seems consistent with the literature.
Further research is advised to compare the outcome of this questionnaire with
other research methods, and to check if the questionnaire is sensitive enough and
whether its conclusions are useful in practice.
PMID- 28411733
TI - Can an aircraft be piloted via sonification with an acceptable attentional cost?
A comparison of blind and sighted pilots.
AB - In the aeronautics field, some authors have suggested that an aircraft's attitude
sonification could be used by pilots to cope with spatial disorientation
situations. Such a system is currently used by blind pilots to control the
attitude of their aircraft. However, given the suspected higher auditory
attentional capacities of blind people, the possibility for sighted individuals
to use this system remains an open question. For example, its introduction may
overload the auditory channel, which may in turn alter the responsiveness of
pilots to infrequent but critical auditory warnings. In this study, two groups of
pilots (blind versus sighted) performed a simulated flight experiment consisting
of successive aircraft maneuvers, on the sole basis of an aircraft sonification.
Maneuver difficulty was varied while we assessed flight performance along with
subjective and electroencephalographic (EEG) measures of workload. The results
showed that both groups of participants reached target-attitudes with a good
accuracy. However, more complex maneuvers increased subjective workload and
impaired brain responsiveness toward unexpected auditory stimuli as demonstrated
by lower N1 and P3 amplitudes. Despite that the EEG signal showed a clear
reorganization of the brain in the blind participants (higher alpha power), the
brain responsiveness to unexpected auditory stimuli was not significantly
different between the two groups. The results suggest that an auditory display
might provide useful additional information to spatially disoriented pilots with
normal vision. However, its use should be restricted to critical situations and
simple recovery or guidance maneuvers.
PMID- 28411734
TI - HRI usability evaluation of interaction modes for a teleoperated agricultural
robotic sprayer.
AB - Teleoperation of an agricultural robotic system requires effective and efficient
human-robot interaction. This paper investigates the usability of different
interaction modes for agricultural robot teleoperation. Specifically, we examined
the overall influence of two types of output devices (PC screen, head mounted
display), two types of peripheral vision support mechanisms (single view,
multiple views), and two types of control input devices (PC keyboard, PS3
gamepad) on observed and perceived usability of a teleoperated agricultural
sprayer. A modular user interface for teleoperating an agricultural robot sprayer
was constructed and field-tested. Evaluation included eight interaction modes:
the different combinations of the 3 factors. Thirty representative participants
used each interaction mode to navigate the robot along a vineyard and spray grape
clusters based on a 2 * 2 * 2 repeated measures experimental design. Objective
metrics of the effectiveness and efficiency of the human-robot collaboration were
collected. Participants also completed questionnaires related to their user
experience with the system in each interaction mode. Results show that the most
important factor for human-robot interface usability is the number and placement
of views. The type of robot control input device was also a significant factor in
certain dependents, whereas the effect of the screen output type was only
significant on the participants' perceived workload index. Specific
recommendations for mobile field robot teleoperation to improve HRI awareness for
the agricultural spraying task are presented.
PMID- 28411735
TI - A practical review of energy saving technology for ageing populations.
AB - Fuel poverty is a critical issue for a globally ageing population. Longer
heating/cooling requirements combine with declining incomes to create a problem
in need of urgent attention. One solution is to deploy technology to help elderly
users feel informed about their energy use, and empowered to take steps to make
it more cost effective and efficient. This study subjects a broad cross section
of energy monitoring and home automation products to a formal ergonomic analysis.
A high level task analysis was used to guide a product walk through, and a
toolkit approach was used thereafter to drive out further insights. The findings
reveal a number of serious usability issues which prevent these products from
successfully accessing an important target demographic and associated energy
saving and fuel poverty outcomes. Design principles and examples are distilled
from the research to enable practitioners to translate the underlying research
into high quality design-engineering solutions.
PMID- 28411736
TI - Masked priming for the comparative evaluation of camouflage conspicuity.
AB - Human observer test and evaluation of camouflage patterns is critical for
understanding relative pattern conspicuity against a range of background scenes.
However, very few validated methodologies exist for this purpose, and those that
do carry several limitations. Five experiments examined whether masked priming
with a dot probe could be used to reliably differentiate camouflage patterns. In
each experiment, participants were primed with a camouflaged target appearing on
the left or right of the screen, and then made a speeded response to a dot probe
appearing on the same (congruent) or different (incongruent) side. Across
experiments we parametrically varied prime duration between 35, 42, 49, 56, and
63 ms. Results demonstrated that as prime duration increased, a response time
disadvantage for incongruent trials emerged with certain camouflage patterns.
Interestingly, the most conspicuous patterns showed behavioral differences at a
relatively brief (49 ms) prime duration, whereas behavioral differences were only
found at longer prime durations for less conspicuous patterns; this overall
results pattern matched that predicted by a visual salience model. Together, we
demonstrate the viability of masked priming for the test and evaluation of
camouflage patterns, and correlated outcomes for saliency models and primed
object processing.
PMID- 28411737
TI - Neck posture during lifting and its effect on trunk muscle activation and lumbar
spine posture.
AB - Neck and head posture have been found to have a significant influence on the
posture of the lower spine region during lifting and both an extended/upward gaze
and a flexed/downward gaze have been hypothesized to lead to increased pain
and/or overuse of the neck musculature. As a result, strength training
recommendations have turned to the use of a retracted neck posture as being the
safer posture to assume during lifting. This study examined trunk and neck muscle
activity and lumbar spine posture in seven participants while performing moderate
load lifts using a retracted neck posture (chin drawn in posteriorly; recently
gaining popularity among coaches, trainers, and physical therapists to reduce
neck pain during lifting, and freestyle neck posture (no instructions given). The
retracted neck resulted in less lumbar spine flexion and increased lumbar erector
spinae, external oblique, and sternocleidomastoid activity. The retracted posture
also resulted in decreased activity in the thoracic erector spinae and dorsal
neck musculature. The increased trunk and sternocleidomastoid activity and
decreased spine flexion observed in the seven participants of this study when
lifting with a retracted neck may have the potential to help lower the risk of
spine pain/injury.
PMID- 28411738
TI - Implementing powered stretcher and load systems was a cost effective intervention
to reduce the incidence rates of stretcher related injuries in a paramedic
service.
AB - Paramedic services are considering moving towards the use of powered stretcher
and load systems to reduce stretcher related injuries, but cost is perceived as a
barrier. This study compared injury incidence rates, days lost, and compensation
costs between Niagara Emergency Medical Service (NEMS) and Hamilton Paramedic
Service (HPS) pre- (four years) and post- (one year) implementation of powered
stretcher and load systems in NEMS. Prior to the intervention stretcher related
musculoskeletal disorder (MSD) incidence rates averaged 20.0 (+/-6.8) and 17.9
(+/-6.4) per 100 full time equivalent (FTE), in NEMS and HPS respectively. One
year post intervention rates decreased to 4.3 per 100 FTE in NEMS, a 78%
reduction. Rates modestly increased to 24.6 per 100 FTE in HPS in same period.
Cost-benefit analysis estimated that the added cost to purchase powered stretcher
and load systems would be recovered within their expected 7-year service life due
to the reduction in compensation costs.
PMID- 28411739
TI - Qualitative ergonomics/human factors research in health care: Current state and
future directions.
AB - The objective of this systematic review was to understand the current state of
Ergonomics/Human Factors (E/HF) qualitative research in health care and to draw
implications for future efforts. This systematic review identified 98 qualitative
research papers published between January 2005 and August 2015 in the seven
journals endorsed by the International Ergonomics Association with an impact
factor over 1.0. The majority of the studies were conducted in hospitals and
outpatient clinics, were focused on the work of formal health care professionals,
and were classified as cognitive or organizational ergonomics. Interviews, focus
groups, and observations were the most prevalent forms of data collection.
Triangulation and data archiving were the dominant approaches to ensuring rigor.
Few studies employed a formal approach to qualitative inquiry. Significant
opportunities remain to enhance the use of qualitative research to advance
systems thinking within health care.
PMID- 28411740
TI - Optimal bus temperature for thermal comfort during a cool day.
AB - A challenge for electric buses is to minimize heating and cooling power to
maximally extend the driving range, but still provide sufficient thermal comfort
for the driver and passengers. Therefore, we investigated the thermal sensation
(TS) and thermal comfort (TC) of passengers in buses during a cool day
(temperature 13.4 +/- 0.5 degrees C, relative humidity (RH) 60 +/- 5.8%) typical
for the Dutch temperate maritime climate. 28 Males and 72 females rated TS and TC
and gave information on age, stature, body weight and worn garments. The
temperature in the bus of 22.5 +/- 1.1 degrees C and RH of 59.9 +/- 5.8%
corresponded to a slightly warm feeling (TS = 0.85 +/- 1.06) and TC of 0.39 +/-
0.65. TS related significantly to bus temperature, clothing insulation and age.
Linear regression based on these parameters showed that the temperature in the
bus corresponding to TC = 0 and TS = 0 would have been 20.9 +/- 0.6 degrees C.
In conclusion, a 1.6 degrees C lower bus temperature during the investigated
cool day probably would have led to less thermal discomfort and energy savings of
electrical busses. The methodology to relate climatic measurements to subjective
assessments is currently employed in a wider climatic range and may prove to be
useful to find a better balance between thermal comfort and energy savings of the
bus.
PMID- 28411741
TI - Required friction during overground walking is lower among obese compared to non
obese older men, but does not differ with obesity among women.
AB - Obesity and aging have been independently associated with altered required
friction during walking, but it is unclear how these factors interact to
influence the likelihood of slipping. Therefore, the purpose of this study was to
determine whether there are differences related to obesity and aging on required
friction during overground walking. Fourteen older non-obese, 11 older obese, 20
younger non-obese, and 20 younger obese adults completed walking trials at both a
self-selected and hurried speed. When walking at a hurried speed, older obese men
walked at a slower gait speed and exhibited lower frictional demands compared
both to older non-obese men and to younger obese men. No differences in required
friction were found between non-obese and obese younger adults. These results
suggest that the increased rate of falls among obese or older adults is not
likely due to a higher risk of slip initiation.
PMID- 28411742
TI - A biomechanical and physiological study of office seat and tablet device
interaction.
AB - Twenty subjects performed typing tasks on a desktop computer and touch-screen
tablet in two chairs for an hour each, and the effects of chair, device, and
their interactions on each dependent measure were recorded. Biomechanical
measures of muscle force, spinal load, and posture were examined, while
discomfort was measured via heart rate variability (HRV) and subjective reports.
HRV was sensitive enough to differentiate between chair and device interactions.
Biomechanically, a lack of seat back mobility forced individuals to maintain an
upright seating posture with increased extensor muscle forces and increased
spinal compression. Effects were exacerbated by forward flexion upon interaction
with a tablet device or by slouching. Office chairs should be designed with both
the human and workplace task in mind and allow for reclined postures to off-load
the spine. The degree of recline should be limited, however, to prevent decreased
lumbar lordosis resulting from posterior hip rotation in highly reclined
postures.
PMID- 28411743
TI - Psychophysiological responses to short-term cooling during a simulated monotonous
driving task.
AB - For drivers on monotonous routes, cognitive fatigue causes discomfort and poses
an important risk for traffic safety. Countermeasures against this type of
fatigue are required and thermal stimulation is one intervention method.
Surprisingly, there are hardly studies available to measure the effect of cooling
while driving. Hence, to better understand the effect of short-term cooling on
the perceived sleepiness of car drivers, a driving simulator study (n = 34) was
conducted in which physiological and vehicular data during cooling and control
conditions were compared. The evaluation of the study showed that cooling applied
during a monotonous drive increased the alertness of the car driver. The
sleepiness rankings were significantly lower for the cooling condition.
Furthermore, the significant pupillary and electrodermal responses were
physiological indicators for increased sympathetic activation. In addition,
during cooling a better driving performance was observed. In conclusion, the
study shows generally that cooling has a positive short-term effect on drivers'
wakefulness; in detail, a cooling period of 3 min delivers best results.
PMID- 28411744
TI - Effects of transit bus interior configuration on performance of wheeled mobility
users during simulated boarding and disembarking.
AB - The emergence of low-floor bus designs and related regulatory standards in the
U.S. have resulted in substantial improvements in public transit accessibility.
However, passengers using wheeled mobility devices still experience safety
concerns and inefficiencies in boarding, disembarking, and interior circulation
on low-floor buses. This study investigates effects of low-floor bus interior
configuration and passenger crowding on boarding and disembarking efficiency and
safety. Users of manual wheelchairs (n = 18), powered wheelchairs (n = 21) and
electric scooters (n = 9) simulated boarding and disembarking in three interior
layout configurations at low and high passenger crowding conditions on a full
scale laboratory mock-up of a low-floor bus. Dependent measures comprised task
times and critical incidents during access ramp use, fare payment, and movement
to and from the doorway and wheeled mobility securement area. Individual times
for unassisted boarding ranged from 15.2 to 245.3 s and for disembarking ranged
from 9.1 to 164.6 s across layout and passenger crowding conditions.
Nonparametric analysis of variance showed significant differences and
interactions across vehicle design conditions, passenger load and mobility device
type on user performance. The configuration having electronic on-board fare
payment, rear-bus entrance doorways and adjacent device securement areas
demonstrated greatest efficiency and safety. High passenger load adversely
impacted efficiency and frequency of critical incidents during on-board
circulation across all three layouts. Findings have broader implications for
improving transit system efficiency and quality of service across the spectrum of
transit users.
PMID- 28411745
TI - When the going gets tough, the tough go colder!
PMID- 28411746
TI - The art of repair.
PMID- 28411747
TI - The impact of carotid or intracranial atherosclerosis on perioperative stroke in
patients undergoing open aortic arch surgery.
AB - OBJECTIVES: This study aimed to clarify the impact of carotid or intracranial
atherosclerosis on perioperative stroke in patients undergoing open aortic arch
surgery. METHODS: Between 2008 and 2015, 200 consecutive patients underwent
elective aortic arch surgery with selective antegrade cerebral perfusion and
moderate hypothermic circulatory arrest. Nonselective screening for carotid or
intracranial atherosclerosis was performed using carotid ultrasonography or
magnetic resonance angiography. Carotid or intracranial atherosclerosis was
classified as below moderate (0%-49% stenosis), moderate (50%-69%), or severe
(70%-100%). In patients with moderate or severe stenosis, cerebral hemodynamics
were evaluated using single-photon emission computed tomography with
acetazolamide. RESULTS: None of the 37 patients undergoing preoperative single
photon emission computed tomography with acetazolamide had impaired cerebral
hemodynamics. In-hospital mortality rate was 3.5% (7/200). Postoperative
neurologic morbidity included permanent stroke in 8 patients (4.0%) and transient
neurologic deficits in 27 patients (14%). Permanent stroke occurred in 3 of 159
patients (1.9%) with below moderate stenosis and 5 of 41 patients (12.2%) with
moderate or severe stenosis (P = .008). Seven of 8 patients (87.5%) with stroke
experienced multiple atherothrombotic embolizations, and 1 patient experienced a
stroke of unknown cause. In multivariate analysis, previous cerebrovascular
accident (odds ratio, 5.0; 95% confidence interval, 2.07-12.42; P = .0004) and
shaggy aorta (odds ratio, 4.2; 95% confidence interval, 1.58-10.98; P = .0045)
were significant determinants of neurologic morbidity. CONCLUSIONS: Embolism was
the major cause of permanent stroke in our patient population. Preoperative
craniocervical and aortic screening may aid in modifying the operative strategy
to reduce the occurrence of stroke.
PMID- 28411748
TI - Mitral stenosis with pulmonary hypertension: We should operate early.
PMID- 28411749
TI - Pulmonary hypertension and mitral valve disease: Still a beast.
PMID- 28411750
TI - Safety of air travel in the immediate postoperative period after anatomic
pulmonary resection.
AB - OBJECTIVE: The study objective was to determine whether air travel in the
immediate postoperative period after anatomic pulmonary resection is associated
with increased morbidity or mortality. METHODS: All patients undergoing anatomic
pulmonary resection at the Mayo Clinic (2005-2012) were identified and sent
surveys querying their mode of transportation home after hospital dismissal and
any complications encountered during or shortly after this travel. This included
pneumonia, hospital readmission, deep venous thrombosis/pulmonary embolism, and
specific pleural complications (pneumothorax, empyema, or chest tube placement).
We compared the results of patients returning home by conventional ground travel
with the results of patients using air travel. RESULTS: Surveys were sent to 1833
patients, and 817 responded (44.6% response rate). A total of 96 responders
(11.8%) used air travel (median distance, 1783 km; range, 486-9684 km) compared
with 278 km (range, 1-2618 km) for the 721 responders (88.2%) using ground travel
(P < .0001). Male patients used air travel more than female patients (14.4% vs
9.3%; P = .02). Otherwise, no significant differences were observed between the 2
groups. The median duration of hospitalization was 5 days in both groups using
air travel (range, 1-25 days) and ground travel (range, 1-42 days) (P = .83).
There was no mortality due to postdismissal travel. The rates of major
complication after hospital dismissal for those using air and ground travel were
8.3% and 7.8%, respectively (P = .87). CONCLUSIONS: Overall major complications
are rare in the immediate posthospital dismissal period after lung resection. Air
travel during this period was not associated with any significant increase in
risk of complications when compared with conventional ground transportation and
seems to be a safe option for patients after chest tube removal.
PMID- 28411751
TI - Notice of Correction.
PMID- 28411752
TI - Complex homograft aortic reconstruction: New recipes from old ingredients.
PMID- 28411753
TI - 2016 update to The American Association for Thoracic Surgery (AATS) consensus
guidelines: Ischemic mitral valve regurgitation.
PMID- 28411754
TI - New common ground: EUS-guided portal pressure measurements as a bridge between
endoscopy and hepatology.
PMID- 28411755
TI - Combination pharmacoprophylaxis for post-ERCP pancreatitis: working toward an
evidence base.
PMID- 28411756
TI - Pancreatic cyst guidelines: Which one to live by?
PMID- 28411757
TI - Impact of endoscopist training on postcolonoscopy colorectal cancer rate.
PMID- 28411758
TI - Postcolonoscopy colorectal carcinoma.
PMID- 28411759
TI - Response.
PMID- 28411760
TI - Erratum.
PMID- 28411761
TI - EUS-guided biliary drainage: moving into a new era of biliary drainage.
PMID- 28411762
TI - POEM outcomes: How long is long enough?
PMID- 28411763
TI - Is timing everything in the management of acute upper GI bleeding?
PMID- 28411764
TI - Early gastric cancer in super-agers: To treat or not to treat?
PMID- 28411765
TI - Hepatic artery disease and anastomotic bile leaks after liver transplantation:
shining the light on the true Achilles' heel.
PMID- 28411766
TI - A review of the impact of patch testing on quality of life in allergic contact
dermatitis.
PMID- 28411767
TI - Low risk of hemorrhagic complications after obtaining diagnostic skin biopsy
specimens in a cohort of thrombocytopenic inpatients.
PMID- 28411768
TI - Who wrote this paper? The ethical issues of authorship.
PMID- 28411769
TI - Introducing the JAAD Virtual Journal Club.
PMID- 28411770
TI - Erratum to "Reporting adverse events related to cosmetic products".
PMID- 28411771
TI - Psychocutaneous disease: Clinical perspectives.
AB - Psychocutaneous disease, defined in this review as primary psychiatric disease
with skin manifestations, is commonly encountered in dermatology. Dermatologists
can play an important role in the management of psychocutaneous disease because
patients visit dermatology for treatment of their skin problems but often refuse
psychiatric intervention. This review describes common psychocutaneous syndromes,
including delusional, factitious, obsessive-compulsive and related, and eating
disorders, as well as psychogenic pruritus, cutaneous sensory (pain) syndromes,
posttraumatic stress disorder, and sleep-wake disorders. The updated
classification of these disorders in the Diagnostic and Statistical Manual of
Mental Disorders, 5th edition is included. Strategies for management are
reviewed.
PMID- 28411772
TI - Psychocutaneous disease: Pharmacotherapy and psychotherapy.
AB - Building a strong therapeutic alliance with the patient is of utmost importance
in the management of psychocutaneous disease. Optimal management of
psychocutaneous disease includes both pharmacotherapy and psychotherapy. This
article reviews psychotropic medications currently used for psychocutaneous
disease, including antidepressants, antipsychotics, mood stabilizers, and
anxiolytics, with a discussion of relevant dosing regimens and adverse effects.
Pruritus management is addressed. In addition, basic and complex forms of
psychotherapy, such as cognitive-behavioral therapy and habit-reversal training,
are described.
PMID- 28411773
TI - Commentary: The quest for an improved risk stratification tool for patients with
melanoma.
PMID- 28411774
TI - Nail removal in pachyonychia congenita: Patient-reported survey outcomes.
PMID- 28411775
TI - Comparing the sensitivity of auramine-rhodamine fluorescence to polymerase chain
reaction in the detection of Mycobacterium leprae in Fite-negative tissue
sections.
PMID- 28411776
TI - Establishment of a dermatology global health outreach and residency partnership
program in Guatemala.
PMID- 28411777
TI - A survey-based study of management of longitudinal melanonychia amongst attending
and resident dermatologists.
PMID- 28411778
TI - Lack of efficacy of topical timolol for cutaneous telangiectasias in patients
with hereditary hemorrhagic telangiectasia: Results of a pilot study.
PMID- 28411779
TI - Prescribing propranolol for infantile hemangioma: Assessment of dosing errors.
PMID- 28411788
TI - Intralesional corticosteroid therapy for relapsing polychondritis.
PMID- 28411789
TI - Significant cost savings from treating peristomal irritant contact dermatitis
with an over-the-counter spray.
PMID- 28411790
TI - The use of gentian violet 2% solution to identify holes in the deep margin of
tissue excised during Mohs micrographic surgery.
PMID- 28411791
TI - Preventing disruption of surgical dressings in patients with cognitive
impairment.
PMID- 28411792
TI - Surgical staples for hemostasis during scalp surgery.
PMID- 28411793
TI - Conclusions about atopic dermatitis persistence might be premature.
PMID- 28411794
TI - Reply to: "Conclusions about atopic dermatitis persistence might be premature".
PMID- 28411795
TI - Heterogeneity of data included in meta-analysis on persistence of atopic
dermatitis changes interpretation.
PMID- 28411796
TI - Reply to: "Heterogeneity of data included in meta-analysis on persistence of
atopic dermatitis alters interpretation".
PMID- 28411797
TI - A label-free fluorescence turn-on assay for glutathione detection by using MnO2
nanosheets assisted aggregation-induced emission-silica nanospheres.
AB - Glutathione (GSH) serves several vital biological functions and its abnormal
levels are associated with many diseases. Simple and sensitive methods capable of
detecting GSH are desired for better understanding the mechanism of diseases. In
this work, a label-free MnO2 nanosheets assisted aggregation-induced emission
(AIE)-silica nanospheres (SiO2 NPs) nanoprobe for fluorescent "turn-on" detection
of GSH with high sensitivity was reported for the first time. The anionic
tetraphenylethylene derivative 3 (TPE3) was synthesized and employed as the AIE
active probe, which can be aggregated on the uncoated amino-functionalized SiO2
NPs to form AIE-SiO2 NPs and emitted strong fluorescence. Negatively charged MnO2
nanosheets were employed as both positive charge protectors for amino
functionalized SiO2 NPs and recognition units for GSH. The presence of GSH could
selectively reduce MnO2 nanosheets to Mn2+, thus releasing the amino
functionalized SiO2 NPs and exposure its positive charges. Accordingly, the TPE3
could be aggregated on the exposured amino-functionalized SiO2 NPs to form AIE
SiO2 NPs and emitted strong fluorescence. The proposed assay is simple, fast, low
cost, and highly sensitive with a detection limit of 200nM for GSH. The assay was
further applied in human serum samples for the detection of GSH with satisfactory
results, demonstrating its promising application in practical biological samples.
PMID- 28411798
TI - Polyelectrolyte mediated nano hybrid particle as a nano-sensor with outstandingly
amplified specificity and sensitivity for enzyme free estimation of cholesterol.
AB - As a proof of concept, here it is established that curcumin integrated chitosan
oligosaccharide lactate (COL) self-assembles on silica nanoparticle surface to
form nano hybrid particles (NHPs). These NHPs have size in the ranges of 25-35nm
with silica nanoparticle as its core and curcumin-COL as outer layer having
thickness of 4-8nm. The fluorescence intensity of these NHPs are found to be
quenched and emission maximum is ~50nm red shifted compared to free curcumin
implying inner filter effect and/or homo-FRET between curcumin molecules present
on the surface of individual nano hybrid particle. Although fluorescence of free
curcumin is remarkably quenched by Hg2+/Cu2+ ions due to chelation through keto
enol form, the fluorescence of NHPs is unaffected by Hg2+/Cu2+ ion that boosts
analytical selectivity. The fluorescence intensity is outstandingly enhanced in
the presence of cholesterol but is not influenced by ascorbic acid, uric acid,
glucose, albumin, lipid and other potential interfering substances that either
obstruct during enzymatic reaction or affect fluorescence of free curcumin. Thus,
NHPs outstandingly improve analytical specificity, selectivity and sensitivity
during cholesterol estimation compared to free curcumin. The interaction between
cholesterol and NHPs is found to be a combination of ground state electrostatic
interaction through the free hydroxyl group of cholesterol along with hydrophobic
interaction between NHPs and cholesterol and excited state interaction. The
proposed cholesterol biosensor illustrates a wider linear dynamic range, 0.002
10mmolL-1, (upper limit is due to lack of solubility of cholesterol) needed for
biomedical application and better than reported values during enzymatic reaction.
In addition, the NHPs are found to be photo-stable potentially making it suitable
for simple, quick and cost-effective cholesterol estimation and opening an
alternative approach other than enzymatic reaction using nano hybrid structure to
tune analytical specificity, selectivity and sensitivity of probe molecule.
PMID- 28411799
TI - Selective detection of ZnO nanoparticles in aqueous suspension by capillary
electrophoresis analysis using dithiothreitol and L-cysteine adsorbates.
AB - The UV detection sensitivity of ZnO nanoparticles in capillary electrophoresis
(CE) analysis was selectively enhanced, by 27 or 19 folds, after adsorption of
dithiothreitol (DTT) or cysteine (Cys) in 10mM sodium phosphate buffer.
Adsorption equilibrium was reached within 90min for DTT but only 10min for Cys.
The adsorption process was best modeled by the Langmuir isotherm, indicating the
formation of a monolayer of DTT or Cys on the surface of ZnO nanoparticles. The
selectivity of DTT and Cys towards ZnO nanoparticles was tested using alumina
(Al2O3), ceria (CeO2), silica (SiO2) and titania (TiO2) nanoparticles. No changes
in the CE-UV peak area of either adsorbates or nanoparticles were observed,
indicating a lack of adsorption. Dynamic light scattering (DLS) provided similar
evidence of the selectivity of both adsorbates towards ZnO. Cys also improved the
colloidal stability of ZnO nanoparticles by breaking down the aggregates, as
evidenced by a reduction of their average hydrodynamic diameter. This new
analytical approach provides a simple and rapid methodology to detect ZnO
nanoparticles selectively by CE-UV analysis with enhanced sensitivity.
PMID- 28411800
TI - Quantification of copper content with laser induced breakdown spectroscopy as a
potential indicator of offal adulteration in beef.
AB - Laser induced breakdown spectroscopy (LIBS) is an emerging technique in the field
of food analysis which provides various advantages such as minimal sample
preparation, chemical free, rapid detection, provision of spatial information and
portability. In this study, LIBS was employed for quantitative analysis of copper
content in minced beef samples spiked with beef liver over three independent
batches. Copper content was determined with graphite furnace atomic absorption
spectroscopy (GFAAS) in order to obtain reference values for modelling. Partial
least square regression (PLSR) was performed to build a calibration and
validation model. A calibration model with a high Rcv2 of 0.85 and a RMSECV of
43.5ppm was obtained, confirming a good fit for the model. The validation model
showed a good prediction accuracy with a high Rp2 of 0.85 and RMSEP of 36.8ppm.
Moreover, on a further study to evaluate the spatial capabilities, LIBS was able
to successfully map copper content within a pellet, indicating the suitability of
LIBS to provide spatial information and therefore potential use on heterogeneous
samples. Overall, it can be concluded that LIBS combined with chemometrics
demonstrates potential as a quality monitoring tool for the meat processing
industry.
PMID- 28411801
TI - Optimization of gold nanoparticle-based real-time colorimetric assay of
dipeptidyl peptidase IV activity.
AB - Dipeptidyl peptidase IV (DPP-IV also referred to as CD-26) is a serine protease
enzyme with remarkable diagnostic and prognostic value in a variety of health and
disease conditions. Herein, we describe a simple and real-time colorimetric assay
for DPP-IV/CD-26 activity based on the aggregation of gold nanoparticles (AuNPs)
functionalized with the peptide substrates: Gly-Pro-Asp-Cys (GPDC) or Val-Pro
ethylene diamine-Asp-Cys (VP-ED-DC). Cleavage of the substrates by DPP-IV
resulted in aggregation of the AuNPs with accompanying color change in the
solution from red to blue that was monitored using either a UV-visible
spectrophotometer or by the naked eye. Factors, such as time course of the
reaction, stability of the functionalized AuNPs and the structure of the
substrate that influence the cleavage reaction in solution were investigated. The
effects of potential interference from serum proteins (lysozyme, thrombin and
trypsin) on the analytical response were negligible. The detection limits when
GPDC or VP-EN-DC functionalized AuNPs were used for DPP-IV assay were 1.2U/L and
1.5U/L, respectively. The VP-EN-DC method was preferred for the quantitative
determination of DPP-IV activity in serum because of its wide linear range 0
30U/L compared to 0-12U/L for the GPDC assay. Recoveries from serum samples
spiked with DPP-IV activity, between 5 and 25U/L, and using the VP-EN-DC modified
AuNPs method ranged between 83.6% and 114.9%. The two colorimetric biosensors
described here are superior to other conventional methods because of their
simplicity, stability, selectivity and reliability.
PMID- 28411802
TI - Protein separation through preliminary experiments concerning pH and salt
concentration by tube radial distribution chromatography based on phase
separation multiphase flow using a polytetrafluoroethylene capillary tube.
AB - Protein mixtures were separated using tube radial distribution chromatography
(TRDC) in a polytetrafluoroethylene (PTFE) capillary (internal diameter=100um)
separation tube. Separation by TRDC is based on the annular flow in phase
separation multiphase flow and features an open-tube capillary without the use of
specific packing agents or application of high voltages. Preliminary experiments
were conducted to examine the effects of pH and salt concentration on the phase
diagram of the ternary mixed solvent solution of water-acetonitrile-ethyl acetate
(8:2:1 volume ratio) and on the TRDC system using the ternary mixed solvent
solution. A model protein mixture containing peroxidase, lysozyme, and bovine
serum albumin was analyzed via TRDC with the ternary mixed solvent solution at
various pH values, i.e., buffer-acetonitrile-ethyl acetate (8:2:1 volume ratio).
Protein was separated on the chromatograms by the TRDC system, where the elution
order was determined by the relation between the isoelectric points of protein
and the pH values of the solvent solution.
PMID- 28411803
TI - A quantitative method for detecting DNA methylation over targeted genomic regions
using isotope dilution liquid chromatography tandem mass spectrometry.
AB - Aberrant DNA methylation is associated with various diseases. Quantitative
analysis of regional DNA methylation levels of some specific genes would aid in
diseases diagnosis and risk stratification. In this study, we developed a robust
method for detecting DNA methylation level over targeted genomic regions using
nucleobases quantification in bisulfite amplicons by isotope dilution liquid
chromatography tandem mass spectrometry coupled with a simple equation. This
method had wide detection range (from 0% to 100% methylation) and high accuracy
while more time-saving compared to clonal bisulfite sequencing method. The
application for clinical tissue samples showed good applicability and cost
effectiveness. This analytical method is suitable for quantifying average DNA
methylation level over targeted genomic regions and expected to be a useful tool
for detecting DNA methylation biomarkers.
PMID- 28411804
TI - Carrot-derived carbon dots modified with polyethyleneimine and nile blue for
ratiometric two-photon fluorescence turn-on sensing of sulfide anion in
biological fluids.
AB - In this article, a facile and green synthesis of carbon dots (CDs) was developed
by using natural carrot as new carbon source. After direct hydrothermal
carbonization for 5h at 180 degrees C, CDs were prepared facilely. Then, CDs were
conjugated with polyethyleneimine (PEI) and Nile Blue (NB) chloride to produce
CDs/PEI/NB nanocomposites under electrostatic interactions. Upon excitation at
800nm, two-photon fluorescence (TPF) of the nanocomposites was observed, with TPF
peaks of CDs at 415nm and NB at 675nm. The addition of Cu2+ could lead to TPF
quenching of CDs via inner filter effect, but hardly any impacted on TPF of NB.
Afterward, the added S2- combined with Cu2+ to form stable species that caused
the separation of Cu2+ from CDs surface and the TPF recovery of CDs, with
negligible effects on TPF of NB. Herein, a new CDs-based ratiometric TPF turn-on
probe of S2- was developed and showed a good linear relationship (R2 =0.9933)
between ratiometric TPF intensity (I415/I675) and S2- concentration (0.1-8.0MUM),
with a low detection limit of 0.06MUM. This probe was highly selective and
sensitive toward S2- over potential interferences in real biological fluids, with
high detection recoveries.
PMID- 28411805
TI - A ratiometric fluorescent probe for rapid and sensitive detection of biothiols in
fetal bovine serum.
AB - Herein, a ratiometric turn-on fluorescent probe for sensitive detection of
biothiols was designed. The probe consisted of two parts: one was rhodamine B
serving as a fluorescence reference, and the other was coumarin derivative as the
responsive fluorophore with an acrylate group for biothiols recognition. The
response was based on the mechanism of Michael addition and intramolecular
cyclization reaction, and the probe showed ratiometric and sensitive response to
biothiols. Especially, the detection limit of this probe for cysteine was found
to be 0.13MUMU. More importantly, the probe showed the advantage of fast
response, of which the fluorescence intensity can reach the maximum within 10min.
The ratiometric fluorescent probe has been successfully applied for the
determination of biothiols in fetal bovine serum samples and the result was in
good agreement with that tested by Ellman method.
PMID- 28411806
TI - Automated alkaline-induced salting-out homogeneous liquid-liquid extraction
coupled with in-line organic-phase detection by an optical probe for the
determination of diclofenac.
AB - A fully automated alkaline-induced salting-out homogeneous liquid-liquid
extraction (AI-SHLLE) procedure coupled with in-line organic-phase detection by
an optical probe has been suggested. Diclofenac was used as a proof-of-concept
analyte. The method is based on the oxidation of diclofenac with potassium
ferricyanide in an alkaline medium followed by separation of the acetonitrile
phase from the homogeneous sample solution and simultaneous extraction of the
derivative. Sodium hydroxide serves as both the alkaline agent for the
derivatization of diclofenac and as the salting-out agent for the acetonitrile
rich phase formation. Absorbance of the derivative in the acetonitrile-rich phase
was measured in-line using an optical probe. The calibration graph was linear
over the range of 2.5-60umolL-1 with the regression coefficient equal to 0.9997.
The LOD calculated from the calibration plot based on 3sigma was 0.8umolL-1. The
sample throughput was 7 samplesh-1. The method was applied for the determination
of diclofenac in spiked saliva samples and pharmaceutical preparations and the
results were compared with those obtained by the reference method.
PMID- 28411807
TI - A sensitive and disposable indium tin oxide based electrochemical immunosensor
for label-free detection of MAGE-1.
AB - MAGE-1 (MAGE, for melanoma antigen), was identified by virtue of its processing
and cell surface expression as a tumor-specific peptide bound to major
histocompatibility complexes which was reactive with autolytic T cells. 3
Glycidoxypropyltrimethoxysilane (3-GOPS) is frequently employed for the
preparation of dense heterometal hybrid polymers which are used, e.g., for hard
coatings of organic polymers and contact lens materials in the optical industry.
In this study, we have improved a new immunological biosensor with indium tin
oxide (ITO). Then, Anti-MAGE-1 antibody was covalently immobilized with 3-GOPS
which formed a self-assembled monolayers (SAMs) on modified ITO electrodes.
Analytical characteristics such as square wave voltammetry, linear determination
range, repeatability, reproducibility and regeneration of biosensors are
determined. All characterization steps are monitored by electrochemical impedance
spectroscopy (EIS), cyclic voltammetry (CV). The developed biosensor has wide
determination range (0.5fg-15fg/mL). To investigate long shelf life of the
fabricated biosensor, the immunosensors were stored at 4 degrees C for periods
ten weeks. Futhermore, binding kinetics of MAGE1 to antiMAGE-1 is monitored by
single frequency technique in real time. Additionally, Kramer's-Kronig transform
was used to understand whether the impedance spectra of biosensor system are
affected from the variation that occurred because of external factor.
Morphological characteristics of constructed biosensor were observed by scanning
electron microscopy. Real human serum samples were also analyzed by the proposed
biosensor, successfully. A commercial ELISA kit was also used as a reference
method to validate the results obtained by the biosensor. Finally, this biosensor
was tried in real blood sample and that showed it could be utilized in clinical
applications. This biosensor can be preferred due to it has a wide linear range
and it can be prepared easily.
PMID- 28411808
TI - Validation of a new method by nano-liquid chromatography on chip tandem mass
spectrometry for combined quantitation of C3f and the V65 vitronectin fragment as
biomarkers of diagnosis and severity of osteoarthritis.
AB - Microfluidic liquid chromatography coupled to a nanoelectrospray source ion trap
mass spectrometry was used for the absolute and simultaneous quantitation of C3f
and the V65 vitronectin fragment in serum. The method was first carefully
optimized and then validated in serum biological matrix. Stable isotopes for the
two biomarkers of interest were used as stable isotope labeled peptide standards.
A weighted 1/x2 quadratic regression for C3f and a weighted 1/x quadratic
regression for the V65 vitronectin peptide were selected for calibration curves.
Trueness (with a relative bias <10%), precision (repeatability and intermediate
precision <15%) and accuracy (risk <15%) of the method were successfully
demonstrated. The linearity of results was validated in the concentration range
of 2.5-200ng/mL for C3f and 2.5-100ng/mL for the V65 vitronectin fragment. Serum
samples (n=147) classified in 7 groups [(healthy volunteers, OA with 5 grades of
severity and rheumatoid arthritis (RA) patients] were analyzed with our new
quantitative method. Our data confirm that C3f and the V65 vitronectin fragment
are biomarkers of OA severity, but also that C3f fragment is further related to
OA severity whereas the V65 vitronectin fragment is more related to early OA
detection.
PMID- 28411809
TI - Temperature sensing and bio-imaging applications based on polyethylenimine/CaF2
nanoparticles with upconversion fluorescence.
AB - Rare earth ion-doped upconversion nanoparticles (UCNPs) have become a research
hotspot for their applications such as nano-thermometry and bio-imaging. Here we
report one pot solvothermal synthesis of polyethylenimine (PEI) coated CaF2:
1%Er3+, 2%Yb3+ UCNPs with good water-solubility and biocompatibility. The
nanoparticles show a spherical shape with an average size of 40nm and display
intense green light (Yb3+ and Er3+) under the 980nm irradiation. The maximum
sensitivity of temperature sensing in the biological temperature range is
obtained to be 0.00215K-1 using the fluorescence intensity ratio (FIR) technique.
Furthermore, after the UCNPs are incubated with Hela cancer cells for 6h, the
obvious green sign from Er3+ can be observed under the excitation at 980nm. All
the experimental results imply that the PEI/CaF2: 1%Er3+, 2%Yb3+ nanoparticles
are excellent candidates for nano-thermometry and have good potential for
biological applications.
PMID- 28411810
TI - Multivariate curve resolution applied to kinetic-spectroscopic data matrices: Dye
determination in foods by means of enzymatic oxidation.
AB - In this work, the combination of chemometric techniques with kinetic
spectroscopic data allowed quantifying two dyes (tartrazine and carminic acid) in
complex matrices as mustard, ketchup, asparagus soup powder, pumpkin soup powder,
plum jam and orange-strawberry juice. Quantitative analysis was performed without
the use of tedious sample pretreatment, due to the achievement of the second
order advantage. The results obtained showed an improvement in simplicity, speed
and cost with respect to usual separation techniques, allowing to properly
quantifying these dyes obtaining limits of detection below 0.6mgL-1. In addition,
to the best of our knowledge, is the first time that kinetic-spectroscopic data
are obtained from the action of laccase for analytical purposes.
PMID- 28411811
TI - A novel strategy for global mapping of O-GlcNAc proteins and peptides using
selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry
identification.
AB - O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic
and mitochondrial proteins. It serves as a major nutrient sensor to regulate
numerous biological processes including transcriptional regulation, cell
metabolism, cellular signaling, and protein degradation. Dysregulation of
cellular O-GlcNAcylated levels contributes to the etiologies of many diseases
such as diabetes, neurodegenerative disease and cancer. However, deeper insight
into the biological mechanism of O-GlcNAcylation is hampered by its extremely low
stoichiometry and the lack of efficient enrichment approaches for large-scale
identification by mass spectrometry. Herein, we developed a novel strategy for
the global identification of O-GlcNAc proteins and peptides using selective
enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
Standard O-GlcNAc peptides can be efficiently enriched even in the presence of
500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry
with a low nanogram detection sensitivity. This strategy successfully achieved
the first large-scale enrichment and characterization of O-GlcNAc proteins and
peptides in human urine. A total of 474 O-GlcNAc peptides corresponding to 457 O
GlcNAc proteins were identified by mass spectrometry analysis, which is at least
three times more than that obtained by commonly used enrichment methods. A large
number of unreported O-GlcNAc proteins related to cell cycle, biological
regulation, metabolic and developmental process were found in our data. The above
results demonstrated that this novel strategy is highly efficient in the global
enrichment and identification of O-GlcNAc peptides. These data provide new
insights into the biological function of O-GlcNAcylation in human urine, which is
correlated with the physiological states and pathological changes of human body
and therefore indicate the potential of this strategy for biomarker discovery
from human urine.
PMID- 28411812
TI - Quantifying endogenous androgens, estrogens, pregnenolone and progesterone
metabolites in human urine by gas chromatography tandem mass spectrometry.
AB - A method for the quantitation of 22 urinary steroids (androgens, estrogens and
the main pregnenolone and progesterone metabolites) by means of gas
chromatography tandem mass spectrometry using a triple quadrupole analyzer has
been developed. Two different enzymatic hydrolysis protocols were investigated;
one capable of releasing steroids present as both sulfates and glucuronides
(total fraction), and another with beta-glucuronidase activity only. After
selecting adequate internal standards and choosing the optimal instrumental
parameters, i.e. chromatographic separation and ion transition conditions, the
method was fully validated using both hydrolysis protocols. The method was shown
to be linear (r >0.99) in the range of endogenous concentrations for all studied
steroids with extraction recoveries higher than 80%. The use of labeled internal
standards allowed for both a correct quantification and the evaluation of the
rate of deconjugation for sulfates and glucuronides in every sample. In general,
the sensitivity of the method was suitable for the detection of the endogenous
levels, with limits of quantification ranging from 0.1 to 20ng/mL. Accuracies
ranging from 80% to 120%, and relative standard deviations below 25% in intra-
and inter- assay experiments were found for most of the analytes. The
applicability of the validated method was tested by quantifying twenty-two
metabolites in 24-h urine samples collected from healthy individuals. The ranges
for the excretion of steroids in the total and glucuronide fractions obtained
with the new method were compared with those available in the literature. By
comparing the figures in both fractions, an estimation of the percentage that the
sulfation represents for each steroid was also calculated. The presence of side
enzymatic activities and the utility of the method for clinical studies as well
as for doping control analysis is discussed.
PMID- 28411813
TI - Voltammetric determination of trace amounts of diacetyl at a mercury meniscus
modified silver solid amalgam electrode following gas-diffusion microextraction.
AB - A new approach was developed for the determination of trace amounts of diacetyl
in food products using gas-diffusion microextraction (GDME) and subsequent
detection by differential pulse voltammetry (DPV) at a mercury meniscus modified
silver solid amalgam electrode (m-AgSAE). Diacetyl is a vicinal diketone
responsible for the buttery aroma in many fermented foods and beverages. Its
determination is important not only for evaluation of the final product quality
(note of mention: health related concerns were associated with continuous
diacetyl exposure) but also to monitor fermentation. GDME, a technique combining
gas-diffusion and microextraction, particularly aimed to volatile and semi
volatile analytes, seemed the best way to selective extract diacetyl. A solution
of 0.05% o-phenylenediamine (OPDA) prepared in a Britton-Robinson buffer (pH 5.0)
was chosen as the extracting solution. This solution simultaneously extracts, pre
concentrates and derivatizes diacetyl to 2,3-dimethylquinoxaline (DMQ), enhancing
the extraction selectivity and making the analyte electroactive. After finding
the optimum conditions for the extraction process (10min at 60 degrees C with
1.0mL of OPDA at pH 5.0), the DPV measurements at the m-AgSAE were conducted with
a scan rate of 7mVs-1, a modulation amplitude of 50mV and a modulation time of
100ms. Under these conditions, the resulting DMQ could be easily measured at a
potential of -0.6V vs. Ag|AgCl (3molL-1 KCl). The amalgam electrode keeps the
advantages of classic mercury electrodes, like high sensitivity, while being
environmentally friendly. The GDME/m-AgSAE produced suitable method features for
the determination of low amounts of diacetyl (as DMQ) in alcoholic beverages, and
in fact, to the best of our knowledge, the limit of quantification of 0.18ugL-1
is one of the lowest reported in literature.
PMID- 28411814
TI - Nanocoating cellulose paper based microextraction combined with nanospray mass
spectrometry for rapid and facile quantitation of ribonucleosides in human urine.
AB - A rapid and facile analytical method for quantification of ribonucleosides in
human urine was developed by the combination of nanocoating cellulose paper based
microextraction and nanoelectrospray ionization-tandem mass spectrometry (nESI
MS/MS). Cellulose paper used for microextraction was modified by nano-precision
deposition of uniform ultrathin zirconia gel film using a sol-gel process. Due to
the large surface area of the cellulose paper and the strong affinity between
zirconia and the cis-diol compounds, the target analytes were selectively
extracted from the complex matrix. Thus, the detection sensitivity was greatly
improved. Typically, the nanocoating cellulose paper was immersed into the
diluted urine for selective extraction of target analytes, then the extracted
analytes were subjected to nESI-MS/MS detection. The whole analytical procedure
could be completed within 10min. The method was evaluated by the determination of
ribonucleosides (adenosine, cytidine, uridine, guanosine) in urine sample. The
signal intensities of the ribonuclesides extracted by the nanocoating cellulose
paper were greatly enhanced by 136-459-folds compared with the one of the
unmodified cellulose paper based microextraction. The limits of detection (LODs)
and the limits of quantification (LOQs) of the four ribonucleosides were in the
range of 0.0136-1.258MUgL-1 and 0.0454-4.194MUgL-1, respectively. The recoveries
of the target nucleosides from spiked human urine were in the range of 75.64
103.49% with the relative standard deviations (RSDs) less than 9.36%. The results
demonstrate the potential of the proposed method for rapid and facile
determination of endogenous ribonucleosides in urine sample.
PMID- 28411815
TI - Automation of sample processing for ICP-MS determination of 90Sr radionuclide at
ppq level for nuclear technology and environmental purposes.
AB - 90Sr is a widely determined radionuclide for environmental purposes, nuclear
waste control, and can be also monitored in coolants in nuclear reactor plants.
In the developed method, the ICP-MS detection was employed together with sample
processing in sequential injection analysis (SIA) setup, equipped with a lab-on
valve with mechanized renewal of sorbent bed for solid-phase extraction. The
optimized conditions of determination included preconcentration of 90Sr on cation
exchange column and removal of different type of interferences using extraction
Sr-resin. The limit of detection of the developed procedure depends essentially
on the configuration of the employed ICP-MS spectrometer and on the available
volume of the sample to be analyzed. For 1L initial sample volume, the method
detection limit (MDL) value was evaluated as 2.9ppq (14.5BqL-1). The developed
method was applied to analyze spiked river water samples, water reference
materials, and also simulated and real samples of the nuclear reactor coolant.
PMID- 28411816
TI - A novel metal-organic framework composite MIL-101(Cr)@GO as an efficient sorbent
in dispersive micro-solid phase extraction coupling with UHPLC-MS/MS for the
determination of sulfonamides in milk samples.
AB - As a novel material, metal-organic framework/graphite oxide (MIL-101(Cr)@GO) has
great potential for the pretreatment of trace analytes. In the present study, MIL
101(Cr)@GO was synthesized using a solvothermal synthesis method at the nanoscale
and was applied as sorbent in the dispersive micro-solid phase extraction (DMSPE)
for the enrichment of the trace sulfonamides (SAs) from milk samples for the
first time. Several experimental parameters including kinds of sorbents, the
effect of pH, the amount of MIL-101(Cr)@GO, ionic strength, adsorption time,
desorption solvent and desorption time were investigated. Under the optimal
conditions, the linear ranges were from 0.1 to 10MUg/L, 0.2-20MUg/L or 0.5
50MUg/L for the analytes with regression coefficients (r) from 0.9942 to 0.9999.
The limits of detection were between 0.012 and 0.145MUg/L. The recoveries ranged
from 79.83% to 103.8% with relative standard deviations (RSDs)<10% (n=3). MIL
101(Cr)@GO exhibited remarkable advantages compared to MIL-101(Cr), MIL-100(Fe),
activated carbon and other sorbent materials used in pretreatment methods. A
simple, rapid, sensitive, inexpensive and less solvent consuming method of DMSPE
ultra-high performance liquid chromatography-tandem mass spectrometry (DMSPE
UHPLC-MS/MS) was successfully applied to the pre-concentration and determination
of twelve SAs in milk samples.
PMID- 28411817
TI - Trimethyl-beta-cyclodextrin-encapsulated monolithic capillary columns:
Preparation, characterization and chiral nano-LC application.
AB - Trimethylated-beta-cyclodextrin (TM-beta-CD) was encapsulated within several
polymer monolithic capillary columns for reversed-phase chiral nano-liquid
chromatography (nano-LC). The monolithic phases were prepared using the one-pot
in situ copolymerization of ethylene glycol dimethacrylate (EDMA), glycidyl
methacrylate (GMA) monomers and 1-propanol, 1,4-butanediol as progenic solvents
in presence of TM-beta-CD solution within fused silica capillaries (150um I.D.).
The obtained chiral monolithic stationery phases were characterized by scanning
electron microscopy (SEM), N2 adsorption/desorption isotherms, wide angle x-ray
diffraction (WAXRD), thermogravimetric analysis (TGA) and differential thermal
analysis (DTA). The materials characterization demonstrated that monolithic
phases with higher concentration of TM-beta-CD have relatively larger surface
area, smaller pore size and larger total pore volume compared to those with lower
concentration TM-beta-CD. The prepared columns were tested for their
enantioseparation efficiency of a range of racemic pharmaceuticals. The screening
results demonstrated the potential of functionalizing polymer monolithic
stationary phases with TM-beta-CD using the in situ encapsulation approach.
PMID- 28411818
TI - Rapid evaporative ionization mass spectrometry for high-throughput screening in
food analysis: The case of boar taint.
AB - Boar taint is a contemporary off-odor present in meat of uncastrated male pigs.
As European Member States intend to abandon surgical castration of pigs by 2018,
this off-odor has gained a lot of research interest. In this study, rapid
evaporative ionization mass spectrometry (REIMS) was explored for the rapid
detection of boar taint in neck fat. Untargeted screening of samples (n=150)
enabled discrimination between sow, tainted and untainted boars. The obtained
OPLS-DA models showed excellent classification accuracy, i.e. 99% and 100% for
sow and boar samples or solely boar samples, respectively. Furthermore, the
obtained models demonstrated excellent validation characteristics (R2(Y)=0.872
0.969; Q2(Y)=0.756-0.917), which were confirmed by CV-ANOVA (p<0.001) and
permutation testing. In conclusion, in this work for the first time highly
accurate and high-throughput (<10s) classification of tainted and untainted boar
samples was achieved, rendering REIMS a promising technique for predictive
modelling in food safety and quality applications.
PMID- 28411819
TI - An electrochemical bisphenol A sensor based on one step electrochemical reduction
of cuprous oxide wrapped graphene oxide nanoparticles modified electrode.
AB - Bisphenol A (BPA), as an important industrial material, has been widespread
concerned in recent years as its endocrine disrupting effect. This study reported
a novel bisphenol A sensor via a facile one step electrochemical reduction of
graphene oxide (rGO) and cuprous oxide (Cu2O) nanocomposite modified glassy
carbon electrodes. The characterization of the fabricated sensor was performed by
scanning electron microscopy and X-ray spectroscopy. The prepared Cu2O-rGO
electrode presented fast response, high sensitivity and low background current.
The response of BPA on prepared electrode was 2.15 times higher than reduced
graphene modified electrode. Under the optimized experimental parameters, the
detection range of the modified electrode was from 1*10-7 to 8*10-5 M and the
limit of detection was 5.3*10-8 M (S/N =3). The prepared Cu2O-rGO modified
electrode has been successfully used for detecting BPA in environmental water
samples.
PMID- 28411820
TI - Thrombin aptasensor enabled by Pt nanoparticles-functionalized Co-based metal
organic frameworks assisted electrochemical signal amplification.
AB - In this work, a Pt nanoparticles-functionalized Co-based metal organic frameworks
(PtNPs@Co(II)MOFs@PtNPs) was synthesized and applied in electrochemical
aptasensor for thrombin (TB) detection. First, the Co(II)MOFs@PtNPs were prepared
via the mixed solvothermal method, which consists of inner Pt nanoparticles
(PtNPs) encapsulated by aminofunctionalized Co(II)MOFs materials. Following that,
additional PtNPs were adsorbed on the surface of Co(II)MOFs@PtNPs, resulting in
the formation of PtNPs@Co(II)MOFs@PtNPs nanocomposite. The PtNPs@Co(II)MOFs@PtNPs
nanocomposites with a large surface area were implimented as nanocarriers to
immobilize a mass of TBA II for the formation of the TBA II bioconjugates that
could be captured onto the electrode surface by sandwich-type format. Moreover,
the PtNPs@Co(II)MOFs@PtNPs nanocomposites could directly use as redox tags for
charge-generating and electron-transporting with the electron transfer from
Co(II) to Co(III). Furthermore, in the presence of H2O2, the
PtNPs@Co(II)MOF@PtNPs could effectively catalyze H2O2 oxidation with improvement
electron transfer of redox probe, resulting in electrochemical signal
amplification. Based on the above superior advantages, TB was determined in the
concentration range from 0.1pM to 50nM with a detection limit of 0.33fM.
Furthermore, the excellent sensitivity and selectivity can be easily established
for quantitative analysis of other analytes.
PMID- 28411821
TI - Electrochemical discrimination of mints: The last Chinese emperors Kuang Hsu and
Hsuan T'ung monetary unification.
AB - An electrochemical methodology for discriminating monetary emissions, a recurrent
problem in much archaeological studies, is introduced. The method is based on the
record of voltammetric signatures of cuprite and tenorite corrosion products in
the patina using a minimally invasive nanosampling following the voltammetry of
immobilized particles methodology. A model for the depth variation of
voltammetric electrochemical parameters characterizing the composition of the
corrosion patinas is presented. This model permits to rationalize electrochemical
data and discriminate different monetary emissions. The application of this
technique, corroborated by electrochemical impedance spectroscopy (EIS) and
focusing ion beam-field emission scanning electron microscopy (FIB-FESEM-EDX), to
a series of 10 cash copper coins produced around the Kuang Hsu and Hsuan T'ung
last Chinese emperors permits to discern different provincial mints and reveals
that the monetary unification developed in this period was not uniform.
PMID- 28411822
TI - Label-free and sensitive assay for deoxyribonuclease I activity based on
enzymatically-polymerized superlong poly(thymine)-hosted fluorescent copper
nanoparticles.
AB - Deoxyribonuclease I (DNase I) is an important physiological indicator and
diagnostic biomarker, but traditional methods for assessing its activity are time
consuming, laborious, and usually radioactive. Herein, by effectively combining
the special functions of DNase I and terminal deoxynucleotidyl transferase (TdT),
a simple, green, cost-effective, label-free and ultrasensitive assay for DNase I
activity has been constructed based on superlong poly(thymine)-hosted copper
nanoparticles (poly T-CuNPs). In this strategy, a 3'-phosphorylated DNA primer is
designed to block TdT polymerization. After addition of DNase I, the primer could
be digested to release 3'-hydroxylated fragments, which could further be tailed
by TdT in dTTP pool with superlong poly T ssDNA for CuNPs formation. Fluorescence
measurements and gel electrophoresis demonstrated its feasibility for DNase I
analysis. The results indicated that with a size of 3-4nm, the CuNPs templated by
TdT-polymerized superlong poly T (>500 mer) had several advantages such as short
synthetic time (<5min), large Stokes shift (~275nm) and intense red fluorescence
emission. Under the optimal conditions, quantitative detection of DNase I was
realized, showing a good linear correlation between 0.02 and 2.0U/mL (R2=0.9928)
and a detection limit of 0.02U/mL. By selecting six other nucleases or proteins
as controls, an excellent specificity was also verified. Then, the strategy was
successfully applied to detect DNase I in diluted serum with a standard addition
method, thus implying its reliability and practicability for biological samples.
The proposed strategy might be promising as a sensing platform for related
molecular biology and disease studies.
PMID- 28411823
TI - Nucleic acid-controlled quantum dots aggregation: A label-free fluorescence turn
on strategy for alkaline phosphatase detection.
AB - Based on the controlled aggregation of quantum dots (QDs), a valid, reliable, and
label-free fluorescence turn-on strategy is established for the detection of
alkaline phosphatase activity. The aqueous solution of anionic QDs exhibits
intense fluorescence. However, the addition of cationic polymer (poly-1)
significantly quenched the fluorescence of the QDs via their induced aggregation.
While short 3'-phosphorylated DNA (DNA-P) could not be extended by terminal
deoxynucleotidyl transferase (TdT) and therefore, fluorescence of the QDs was
recovered negligibly. The effective elimination of phosphate group of DNA-P in
the presence of alkaline phosphatase (ALP) produced 3'-OH termini and the
resulting DNA could be sufficiently extended by TdT. The presence of greater
binding strength between the elongated DNA and poly-1 is very crucial to compete
with the poly-1/QDs aggregates and release the QDs. Turned-on fluorescence
emission is observed due to the efficient release of the QDs. A novel strategy
for alkaline phosphatase detection is therefore established. Our method is quite
sensitive and selective, as low as 0.1 mU/mL ALP can be easily detected.
PMID- 28411824
TI - Application of benchtop and portable near-infrared spectrometers for predicting
the optimum harvest time of Verbena officinalis.
AB - This study examined the applicability of near-infrared (NIR) spectroscopy coupled
with multivariate data analysis (MVA) to determine the ideal harvest time of
Verbena officinalis. NIR analyses were performed non-invasively on the fresh
plant material based on the quantification of the key constituents verbenalin and
verbascoside. Vibrational spectroscopic measurements were performed applying a
conventional NIR benchtop device as well as a laboratory independent handheld NIR
spectrometer. A novel high performance liquid chromatography (HPLC) method was
applied as a reference method. For both instruments partial least squares (PLS)
regression models were established performing cross validations (CV) and test-set
validations (TSV). Quality parameters obtained for the benchtop device revealed
that the newly established NIR method enabled reliable quantifications of the
main compounds verbenalin and verbascoside related to the dried and fresh plant
material. The results of the miniaturised spectrometer revealed that accurate
quantitative calibration models could be developed for verbascoside achieving a
comparable prediction power to the benchtop device. PLS models for verbenalin
were less precise suggesting the application of portable devices including a
different spectral range and resolution. The work demonstrated the feasibility of
NIR vibrational spectroscopy performing direct measurements on pharmaceutically
relevant fresh plant material enabling a quick and simple determination of the
ideal harvest time of Verbena officinalis.
PMID- 28411825
TI - Volatile profiles of green Spanish-style table olives: Application of
compositional data analysis for the segregation of their cultivars and production
areas.
AB - The work presents the application of compositional data methodology to analytical
results, taking as an example the study of the volatile profiles of green Spanish
style table olives according to cultivars and production areas. For this purpose,
the volatile compounds (analysed by GC-MS and expressed as percentages of the
total area) were considered as a compositional data set in the Simplex space and,
as a result, analysed by their specific new statistical tools. Application of
compositional exploratory tools (variation array, tertiary graphs, biplots, or
coda-dendrogram) allowed differentiating cultivars and production areas based on
their volatile profiles. Also, the application of Cluster and Principal Component
analysis to the ilr transformed values (coordinates), following the new
methodology, led to more realistic results than the formally incorrect
implementation of the standard multivariate analysis (developed for data from the
Euclidean space) to percentages (data in the Simplex). Therefore, the work
presents a novel consideration of the volatile profiles of table olives as
compositional data and shows their proper analysis by statistical tools
specifically developed for them.
PMID- 28411826
TI - A novel fluorescent biosensor for Adenosine Triphosphate detection based on the
polydopamine nanospheres integrating with enzymatic recycling amplification.
AB - Based on the protective performance of polydopamine nanospheres (PDANSs) for DNA
against nuclease digestion and the specific recognition characteristic of
aptamer, we have developed an enzymatic recycling signal amplification method for
highly sensitive and selective detection of adenosine triphosphate (ATP).
Fluorescence measurements were carried out to verify the DNA polymerase and
exonuclease III (Exo III) assisted target recycling process and fluorescence
signal amplification. In the absence of the ATP, initially, the signal DNA-PDANSs
complex was in the "off" state due to the efficient fluorescence quenching of 6
carboxyfluorescein (FAM) adjacent to the surface of PDANSs. Due to the binding of
the aptamer by ATP, it trigger DNA polymerase and Exo III assisted target
recycling process by the product of release, the complex would change into the
"on" state as a result of the dissociation of the FAM from the surface of PDANSs,
thus providing greatly enhanced fluorescence emission intensity. The method
allows quantitative detection of ATP in the range of 20-600nM with a detection
limit of 8.32nM. This biosensor requires no complex operations, and is a new high
efficiency method for ATP detection.
PMID- 28411827
TI - Sensitive determination of malondialdehyde in exhaled breath condensate and
biological fluids by capillary electrophoresis with laser induced fluorescence
detection.
AB - In this work, a sensitive capillary electrophoresis method with laser induced
fluorescence detection for determination of malondialdehyde in various biological
fluids was developed. Malondialdehyde reacts with thiobarbituric acid under
optimized conditions of pH=2, reaction time of 60min and temperature of 90
degrees C, yielding an adduct that can be separated in a 50mM sodium borate
background electrolyte at pH 9. The separation of the formed adduct was
accomplished in less than 6min with limit of detection of 1.1nM due to the use of
532nm laser module, exactly matching the maximum excitation wavelength of the
formed adduct. The developed method offers unprecedented sensitivity and was for
the first time used for analysis of malondialdehyde in exhaled breath condensate.
The method proved to be also applicable to other samples of biological fluids,
such as blood plasma and saliva.
PMID- 28411828
TI - Development of reusable magnetic chitosan microspheres adsorbent for selective
extraction of trace level silver nanoparticles in environmental waters prior to
ICP-MS analysis.
AB - Solid-phase extraction (SPE) based on reusable magnetic chitosan microspheres was
coupled with ICP-MS for separation and quantification of silver nanoparticles
(AgNPs) in the presence of silver ions in environmental water samples. The
monodisperse magnetic chitosan microspheres with an average size of 2um were
engineered using suspension cross-linking technique, and characterized and
investigated for its application as SPE adsorbent. Parameters affecting the SPE
were optimized, and the best performance was achieved by extracting a 20mL sample
(pH 4.5) with 10mg adsorbent for 90min, followed by elution with 1mL 1% (w/v)
thiourea in 10% (v/v) nitric acid for 10min. The detection limit, calculated as
3s (s, standard deviation for 11 blank readings), for three AgNPs coated with
polyvinyl pyrrolidone (PVP), citrate and polyvinyl alcohol (PVA) and sizes of 31,
40, 46nm, respectively, were in the range of 0.016-0.023MUg/L. The repeatability
and reproducibility (RSD, n=7) at a spiking level of 0.1MUg/L AgNPs were 4.2% and
8.1%, respectively. The developed method has been applied in the analysis of
AgNPs in river, lake and wastewater samples, with excellent extraction
efficiencies (84.9-98.8%) for AgNPs at spiking levels of 0.86 and 8.70MUg/L. The
cationic chitosan microspheres showed good species selectivity and reusability
for extraction of AgNPs in the presence of Ag+, and hence the proposed method is
simple, cost effective and environmentally friendly.
PMID- 28411829
TI - Rapid and efficient separation of glycoprotein using pH double-responsive
imprinted magnetic microsphere.
AB - As biomarkers of many diseases, glycoproteins are of great significance to
clinical diagnostics. However, the determination of low abundant glycoproteins in
complex biological samples without any pretreatment process is still a problem.
In this study, a rapid and convenient separation method for highly efficient
enrichment of glycoproteins is reported, based on pH double-responsive imprinted
magnetic microspheres. Thin imprinted polymer shells were fabricated onto the
surface of magnetic microspheres by free radical polymerization, using 2
(Dimethylamino) ethyl methacrylate as pH-sensitive monomer, 4-vinylphenylbronic
acid as boronate affinity monomer, and ovalbumin (OVA) as template molecule.
Combining the advantages of pH-sensitive monomer and boronate affinity monomer,
rapidly capture-release of OVA could be modulated by changing solution pH.
Moreover, high absorption ability (81.2mg/g) was achieved within about 10min.
This study provided responsible way to imprint glycoproteins and showed great
potential for glycoprotein detection in clinical diagnostic.
PMID- 28411830
TI - Leveraging Molecular Data Analysis to Understand Drug Response in Systemic
Sclerosis.
AB - Taroni et al. integrate and analyze genomic information generated from different
clinical trials on systemic sclerosis, a disease for which there is yet no Food
and Drug Administration-approved therapy. By using a recent network analysis
approach based on tissue-specific functionality, they leverage the biological
information extracted from molecular profiling studies and report findings that
could be useful for patient stratification.
PMID- 28411831
TI - Toxic Memories in Systemic Sclerosis.
AB - Systemic sclerosis is an autoimmune disease characterized by T-cell infiltration
in the skin that leads to fibrosis, which can be life-limiting. Although T cells
are important, it is not known which types mediate the fibrosis. The work
presented by Li et al shows that memory CD8+ cytotoxic T cells mediate fibrosis
via the secretion of IL-13. IL-13 is profibrotic, and it is released in a higher
amount in patients with systemic sclerosis. This suggests that targeting IL-13
may be therapeutically beneficial.
PMID- 28411832
TI - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Associations, Outcomes,
and Pathobiology-Thirty Years of Progress but Still Much to Be Done.
AB - Although rare, Stevens-Johnson syndrome and toxic epidermal necrolysis remain
among the most devastating of acute conditions involving the skin. In the past 30
years, tremendous progress has been made in understanding the causes and
pathobiology of this often life-threatening condition. Su et al demonstrate
associations between IL 15 serum levels and the outcome of patients with Stevens
Johnson syndrome and toxic epidermal necrolysis. Their findings provide ideas for
further investigations that may help us better understand the role of cytokines
in this T-cell mediate disease and provides clues to possible new therapies.
PMID- 28411833
TI - Atopic Dermatitis and Comorbidities: Added Value of Comprehensive
Dermatoepidemiology.
AB - Atopic dermatitis is common and in its severe form is devastating. This chronic
inflammatory dermatosis is part of the atopic syndrome, which includes asthma,
food allergies, and hay fever and is known to be associated with mental health
disorders. In line with psoriasis, several recent observational studies using
national survey and linkage data have suggested a link between atopic dermatitis
and cardiovascular disease. The atopic dermatitis field can benefit from the past
experiences in psoriasis research and should not follow the same path, but,
rather, aim for a more comprehensive approach from the beginning. A recent German
consortium studying links between atopic dermatitis and cardiovascular disease
first screened a large claims database, followed by analyses of more deeply
phenotyped (birth) cohorts with longitudinal data. In addition, genetic and
metabolic analyses assessing the predisposition of patients with atopic
dermatitis for cardiovascular disease were performed. Overall, the association
between atopic dermatitis and cardiovascular disease was at most modest, but in
more refined cohorts the cardiovascular risk profile and genetic architecture was
comparable. A more integrated approach could create clarity about the clinical
relevance of cardiovascular disease in individuals with atopic dermatitis sooner,
avoid speculation that affects patient care, and save scientific resources.
PMID- 28411834
TI - Glucocorticoids Inhibit Wound Healing: Novel Mechanism of Action.
AB - Jozic et al. describe mechanisms of glucocorticoid (GC) downregulation of wound
healing by interaction with the membrane bound GC receptor, followed by
stimulation of beta-catenin and c-myc pathways. Targeting the membrane bound GC
receptor or the recently discovered interaction of GC with mineralocorticoid
receptors may counteract negative effects of GC on the skin barrier and
potentially could serve as a remedy for age-related skin atrophy.
PMID- 28411835
TI - Erratum.
PMID- 28411836
TI - The JID in Full Flower.
PMID- 28411837
TI - Doing Good Research Is Difficult, Doing No Research Is More Difficult.
PMID- 28411838
TI - Introduction to JID's Landmarks in the Molecular Revolution.
PMID- 28411839
TI - The Molecular Revolution in Cutaneous Biology: EDC and Locus Control.
AB - The epidermal differentiation complex (EDC) locus consists of a cluster of genes
important for the terminal differentiation of the epidermis. While early studies
identified the functional importance of individual EDC genes, the recognition of
the EDC genes as a cluster with its shared biology, homology, and physical
linkage was pivotal to later studies that investigated the transcriptional
regulation of the locus. Evolutionary conservation of the EDC and the
transcriptional activation during epidermal differentiation suggested a cis
regulatory mechanism via conserved noncoding elements or enhancers. This line of
pursuit led to the identification of CNE 923, an epidermal-specific enhancer that
was found to mediate chromatin remodeling of the EDC in an AP-1 dependent manner.
These genomic studies, as well as the advent of high-throughput sequencing and
genome engineering techniques, have paved the way for future investigation into
enhancer-mediated regulatory networks in cutaneous biology.
PMID- 28411840
TI - The Molecular Revolution in Cutaneous Biology: Noncoding RNAs: New Molecular
Players in Dermatology and Cutaneous Biology.
AB - Progress in genome sequencing achieved during the last two decades revealed that
only about 2% of the genome codes for proteins, while the largest genome fraction
is encoding thousands of non-coding RNAs. Non-coding RNAs play indispensable
roles in regulating the activity and stability of the genome. Recent research in
the area of the non-coding transcriptome signified the crucial roles for RNA
regulatory networks in the normal development and their implications in a variety
of pathological conditions. Here, recent advances in our understanding of non
coding RNA-mediated regulation of skin development and homeostasis are
highlighted, focusing mainly on the regulatory roles of miRNAs and lncRNAs.
PMID- 28411842
TI - The Molecular Revolution in Cutaneous Biology: Investigating the Skin Microbiome.
AB - Building upon the knowledge garnered from investigations utilizing traditional
culturing methods, advances in sequencing technologies have catalyzed a
revolution in studying human-associated microbes: bacteria, fungi and viruses.
Skin microbiome research in healthy individuals and patients with dermatologic
disorders has provided insights into the complexity and biogeography of human
skin microbes. The continual developments in sequencing and analyses will provide
increasingly sophisticated tools to interrogate human-associated microbes,
ultimately to improve our understanding of health and disease.
PMID- 28411841
TI - The Molecular Revolution in Cutaneous Biology: The Era of Genome-Wide Association
Studies and Statistical, Big Data, and Computational Topics.
AB - The investigation of biological systems involving all organs of the body
including the skin is in era of big data. This requires heavy-duty computational
tools, and novel statistical methods. Microarrays have allowed the interrogation
of thousands of common genetic markers in thousands of individuals from the same
population (termed genome wide association studies or GWAS) to reveal common
variation associated with disease or phenotype. These markers are usually single
nucleotide polymorphisms (SNPs) that are relatively common in the population. In
the case of dermatological diseases such as alopecia areata, vitiligo, psoriasis
and atopic dermatitis, common variants have been identified that are associated
with disease, and these provide insights into biological pathways and reveal
possible novel drug targets. Other skin phenotypes such as acne, color and skin
cancers are also being investigated with GWAS. Analyses of such large GWAS
datasets require a consideration of a number of statistical issues including the
testing of multiple markers, population substructure, and ultimately a
requirement for replication. There are also issues regarding the missing
heritability of disease that cannot be entirely explained with current GWAS
approaches. Next generation sequencing technologies such as exome and genome
sequencing of similar patient cohorts will reveal additional variants
contributing to disease susceptibility. However, the data generated with these
approaches will be orders of magnitude greater than that those generated with
arrays, with concomitant challenges in the identification of disease causing
variants.
PMID- 28411843
TI - The Molecular Revolution in Cutaneous Biology: Emerging Landscape in Genomic
Dermatology: New Mechanistic Ideas, Gene Editing, and Therapeutic Breakthroughs.
AB - Stunning technological advances in genomics have led to spectacular breakthroughs
in the understanding of the underlying defects, biological pathways and
therapeutic targets of skin diseases leading to new therapeutic interventions.
Next-generation sequencing has revolutionized the identification of disease
causing genes and has a profound impact in deciphering gene and protein
signatures in rare and frequent skin diseases. Gene addition strategies have
shown efficacy in junctional EB and in recessive dystrophic EB (RDEB). TALENs and
Cripsr/Cas9 have emerged as highly efficient new tools to edit genomic sequences
to creat new models and to correct or disrupt mutated genes to treat human
diseases. Therapeutic approaches have not been limited to DNA modification and
strategies at the mRNA, protein and cellular levels have also emerged, some of
which have already proven clinical efficacy in RDEB. Improved understanding of
the pathogenesis of skin disorders has led to the development of specific drugs
or repurposing of existing medicines as in basal cell nevus syndrome, alopecia
areata, melanoma and EB simplex. These discoveries pave the way for improved
targeted personalized medicine for rare and frequent diseases. It is likely that
a growing number of orphan skin diseases will benefit from combinatory new
therapies in a near future.
PMID- 28411844
TI - Research Techniques Made Simple: Mass Cytometry Analysis Tools for Decrypting the
Complexity of Biological Systems.
AB - Mass cytometry by time-of-flight experiments allow analysis of over 40 functional
and phenotypic cellular markers simultaneously at the single-cell level. The data
dimensionality escalation accentuates limitations, inherent to manual analysis,
as being subjective, labor-intensive, slow, and often incapable of showing the
detailed features of each unique cell within populations. The subsequent
challenge of examining, visualizing, and presenting mass cytometry data has
motivated continuous development of dimensionality reduction methods. As a
result, an increasing recognition of the inherent diversity and complexity of
cellular networks is emerging, with the discovery of unexpected cell
subpopulations, hierarchies, and developmental pathways, such as those existing
within the immune system. Here, we briefly review some frequently used and
accessible mass cytometry data analysis tools, including principal component
analysis (PCA); spanning-tree progression analysis of density-normalized events
(SPADE); t-distributed stochastic neighbor embedding (t-SNE)-based visualization
(viSNE); automatic classification of cellular expression by nonlinear stochastic
embedding (ACCENSE); and cluster identification, characterization, and regression
(CITRUS). Mass cytometry, used together with these innovative analytic tools, has
the power to lead to key discoveries in investigative dermatology, including but
not limited to identifying signaling phenotypes with predictive value for early
diagnosis, prognosis, or relapse and a thorough characterization of intratumor
heterogeneity and disease-resistant cell populations, that may ultimately unveil
novel therapeutic approaches.
PMID- 28411847
TI - The Molecular Revolution in Cutaneous Biology: Era of Cytogenetics and Copy
Number Analysis.
AB - Development of karyotyping techniques in the 1950s sparked groundbreaking reports
of chromosomal aberrations in cancer, such as the Philadelphia chromosome in
chronic myelogenous leukemia in 1960, followed by a number of others. Spatial
resolution of karyotyping is limited and vital tumor cells are required for
metaphase preparation. To overcome these limitations, DNA hybridization
techniques were developed. In situ hybridization of radioactively or fluorescence
labeled RNA probes onto tumor samples allowed the identification of specific
genomic regions, translocations and copy number alterations. However, it is only
suited for a limited number of candidate genes or regions. Genome-wide copy
number analysis was made possible by the development of comparative genomic
hybridization. It compares an entire cancer genome to a normal genome by
differential fluorescence labeling and hybridization onto normal metaphase
chromosomes. Replacing the metaphase chromosomes with arrays of oligonucleotides
significantly increased the resolution. Karyotypic analysis of melanomas could
demonstrate chromosomal aberrations decades ago. However, only CGH allowed
understanding the complex melanoma genomes. Based on mutation analysis and CGH
data, Boris Bastian and his group changed our view of melanoma towards a variety
of genetically distinct tumors. Recent next generation sequencing allows
simultaneous mutation, translocation and copy number analysis, and thereby
accelerates melanoma research.
PMID- 28411848
TI - The Molecular Revolution in Cutaneous Biology: Identification of Skin Disease
Genes.
PMID- 28411850
TI - The Molecular Revolution in Cutaneous Biology: Era of Mosaicism.
PMID- 28411849
TI - The Molecular Revolution in Cutaneous Biology: Keratin Genes and their Associated
Disease: Diversity, Opportunities, and Challenges.
AB - The abundance of keratin proteins and the filaments they form in surface
epithelia has long been appreciated. This said, the remarkable diversity of
keratin proteins and the notion that they are encoded by one of the largest gene
families in the human genome has come to the fore relatively recently, coinciding
with the sequencing of whole genomes. This complexity has generated some
practical challenges, notably in terms of nomenclature and tractability. More
importantly, however, studies of keratin have seeded the discovery of the genetic
basis for a large number of genodermatoses and continue to provide a unique
perspective on and insight into epithelial cells and tissues, whether normal or
diseased.
PMID- 28411851
TI - The Molecular Revolution in Cutaneous Biology: Era of Next-Generation Sequencing.
AB - Like any true conceptual revolution, next-generation sequencing (NGS) has not
only radically changed research and clinical practice, it has also modified
scientific culture. With the possibility to investigate DNA contents of any
organism and in any context, including in somatic disorders or in tissues
carrying complex microbial populations, it initially seemed as if the genetic
underpinning of any biological phenomenon could now be deciphered in an almost
streamlined fashion. However, over the past recent years, we have once again come
to understand that there is no such a thing as great opportunities without great
challenges. The steadily expanding use of NGS and related applications is now
facing biologists and physicians with novel technological obstacles, analytical
hurdles and increasingly pressing ethical questions.
PMID- 28411852
TI - The Molecular Revolution in Cutaneous Biology: Era of Molecular Diagnostics for
Inherited Skin Diseases.
AB - The discovery of pathogenic mutations in inherited skin diseases represents one
of the major landmarks of late 20th century molecular genetics. Mutation data can
provide accurate diagnoses, improve genetic counseling, help define disease
mechanisms, establish disease models, and provide a basis for translational
research and testing of novel therapeutics. The process of detecting disease
mutations, however, has not always been straightforward. Traditional approaches
using genetic linkage or candidate gene analysis have often been limited, costly,
and slow to yield new insights, but the advent of next-generation sequencing
(NGS) technologies has altered the landscape of current gene discovery and
mutation detection approaches.
PMID- 28411853
TI - The Molecular Revolution in Cutaneous Biology: The Era of Global Transcriptional
Analysis.
AB - In the 3 decades since the discovery of the polymerase chain reaction, a
progression of remarkable technical advances has driven great strides in our
understanding of molecular biology such that now we are able to study at once the
entire and complete set of RNA transcripts that are produced by the genome. In
this review, we describe the milestones that have led to this era of global
transcriptional analysis, how these approaches have been extended towards skin
disease, and their future directions.
PMID- 28411855
TI - Single molecule force spectroscopy for in-situ probing oridonin inhibited ROS
mediated EGF-EGFR interactions in living KYSE-150 cells.
AB - As the active anticancer component of Rabdosia Rubescens, oridonin has been
proved to show strong anticancer activity in cancer cells, which is also found to
be closely related to its specific inhibition effects on the EGFR tyrosine kinase
activity. In this study, atomic force microscopy based single molecule force
spectroscopy (AFM-SMFS) was used for real-time and in-situ detection of EGF-EGFR
interactions in living esophageal cancer KYSE-150 cells to evaluate the
anticancer activity of oridonin for the first time. Oridonin was found to induce
apoptosis and also reduce EGFR expression in KYSE-150 cells. AFM-SMFS results
demonstrated that oridonin could inhibit the binding between EGF and EGFR in KYSE
150 cells by decreasing the unbinding force and binding probability for EGF-EGFR
complexes, which was further proved to be closely associated with the
intracellular ROS level. More precise mechanism studies based on AFM-SMFS
demonstrated that oridonin treatment could decrease the energy barrier width,
increase the dissociation off rate constant and decrease the activation energy of
EGF-EGFR complexes in ROS dependent way, suggesting oridonin as a strong
anticancer agent targeting EGF-EGFR interactions in cancer cells through ROS
dependent mechanism. Our results not only suggested oridonin as a strong
anticancer agent targeting EGF-EGFR interactions in ROS dependent mechanism, but
also highlighted AFM-SMFS as a powerful technique for pharmacodynamic studies by
detecting ligand-receptor interactions, which was also expected to be developed
into a promising tool for the screening and mechanism studies of drugs.
PMID- 28411856
TI - Corrigendum to "Hexanal as biomarker for milk oxidative stress induced by copper
ions" (J. Dairy Sci. 100:1650-1656).
PMID- 28411857
TI - Corrigendum to "Health, physiology, and behavior of dairy calves reared on 4
different substrates" (J. Dairy Sci. 100:2148-2156).
PMID- 28411854
TI - The Molecular Revolution in Cutaneous Biology: Chromosomal Territories, Higher
Order Chromatin Remodeling, and the Control of Gene Expression in Keratinocytes.
AB - Three-dimensional organization of transcription in the nucleus and mechanisms
controlling the global chromatin folding, including spatial interactions between
the genes, noncoding genome elements, and epigenetic and transcription machinery,
are essential for establishing lineage-specific gene expression programs during
cell differentiation. Spatial chromatin interactions in the nucleus involving
gene promoters and distal regulatory elements are currently considered major
forces that drive cell differentiation and genome evolution in general, and such
interactions are substantially reorganized during many pathological conditions.
During terminal differentiation of the epidermal keratinocytes, the nucleus
undergoes programmed transformation from highly active status, associated with
execution of the genetic program of epidermal barrier formation, to a fully
inactive condition and finally becomes a part of the keratinized cells of the
cornified epidermal layer. This transition is accompanied by marked remodeling of
the three-dimensional nuclear organization and microanatomy, including changes in
the spatial arrangement of lineage-specific genes, nuclear bodies, and
heterochromatin. This mini-review highlights the important landmarks in the
accumulation of our current knowledge on three-dimensional organization of the
nucleus, spatial arrangement of the genes, and their distal regulatory elements,
and it provides an update on the mechanisms that control higher-order chromatin
remodeling in the context of epidermal keratinocyte differentiation in the skin.
PMID- 28411858
TI - Corrigendum to "Different milk feeding intensities during the first 4 weeks of
rearing dairy calves: Part 2: Effects on the metabolic and endocrine status
during calfhood and around the first lactation" (J. Dairy Sci. 100:3109-3125).
PMID- 28411860
TI - Importance of Accommodation and Eye Dominance for Measuring Objective
Refractions.
PMID- 28411859
TI - CD14 Plays a Protective Role in Experimental Inflammatory Bowel Disease by
Enhancing Intestinal Barrier Function.
AB - Intestinal homeostasis disturbance through intestinal barrier disruption
presumably plays a key role in inflammatory bowel disease (IBD) development.
Genetic and candidate gene analyses in an Il10-deficient IBD mouse model system
identified Cd14 as a potentially protective candidate gene. The role of Cd14 in
colitis development was determined using dextran sulfate sodium (DSS)-induced
acute and an Il10-deficiency-induced chronic model of intestinal inflammation.
Intestinal permeability was investigated by fluorescein isothiocyanate-dextran
uptake assay, quantitative RT-PCR analysis of tight junction proteins, myosin
light chain kinase, and proinflammatory cytokine expression. Immunohistological
staining of occludin, Ki-67, NF-kappaB-p65, and terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling assay was performed, and intestinal
inflammation severity was evaluated histologically. Untreated B6-Cd14-/- mice and
wild-type controls did not differ in intestinal barrier function. However, DSS
treated Cd14-deficient and B6-Il10-/-Cd14-/- mice exhibited more severe
intestinal barrier disruption, with increased histological scores and
proinflammatory cytokine expression, compared to controls. Therefore, Cd14
deficiency did not influence epithelial integrity under steady-state conditions
but caused intestinal barrier dysfunction under inflammation. As expected, CD14
overexpression increased barrier integrity. No difference in intestinal
epithelial NF-kappaB translocation was observed between the investigated groups.
Intestinal myosin light chain kinase expression decreased in Cd14-deficient mice
under steady-state conditions and in the chronic model, whereas no difference was
detected in the DSS models. Thus, CD14 plays a protective role in IBD development
by enhancing intestinal barrier function.
PMID- 28411861
TI - Reply.
PMID- 28411862
TI - Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With
Pseudomonas aeruginosa and Fusarium spp.
AB - Photodynamic therapy (PDT) is a therapeutic modality with significant
antimicrobial activity. We present 2 cases of chronic lower limb ulcers in which
fungal and bacterial superinfection complicated management. PDT with methylene
blue as the photosensitizer led to clinical and microbiological cure with no
significant adverse effects. PDT with methylene blue is a valid option for the
management of superinfected chronic ulcers, reducing the use of antibiotics and
the induction of resistance.
PMID- 28411863
TI - Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?
AB - OBJECTIVE: There is currently no consensus regarding how to address pelvic
sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify
the incidence and clinical impact of PSLNs. METHODS: Retrospective review of a
prospectively collected multi-institutional melanoma database. RESULTS: Of 2476
cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to
both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and
46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal
metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and
SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14%
respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy
upstaged one patient (0.6%), and completion dissection based on a positive PSLN
did not upstage any. CONCLUSIONS: PSLN biopsy is safe, however in the setting of
negative SSLNs there is minimal clinical impact. We therefore recommend PSLN
biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.
PMID- 28411864
TI - Extended anticoagulation in venous thromboembolism disease. In favour.
AB - Venous thromboembolism disease can be considered a chronic disease because, after
the first episode, there is a life-long risk of recurrence. Recurrence is a
severe complication. Anticoagulation is effective while it is maintained, but
when it is discontinued, the risk of new thrombotic events persists indefinitely.
Clinical practice guidelines offer specific recommendations on the treatment
duration for patients with provoked or recurrent disease but are not specific for
those with a first unprovoked episode. The decision should be made after a
careful individual assessment of the risk-benefit of anticoagulation. This
article reviews the evidence in favour of extending the anticoagulation and the
current therapeutic options.
PMID- 28411865
TI - Predicting postoperative outcomes of liver resection by magnetic resonance
elastography.
AB - BACKGROUND: Cirrhosis is associated with blood loss during liver resection and
postoperative complications. The liver stiffness measurement has recently become
available for assessment of liver fibrosis. METHODS: This prospective study was
performed to predict postoperative outcomes of liver resection. The liver
stiffness measurement was measured prospectively using magnetic resonance
elastography for patients who had undergone liver resection for malignancy. We
investigated whether the liver stiffness measurement by magnetic resonance
elastography is correlated with liver fibrosis and postoperative outcomes.
RESULTS: The median liver stiffness measurement by magnetic resonance
elastography in 175 patients was 3.4 (range: 1.5-11.3) kPa, and the pathologic
grade of liver fibrosis was significantly correlated with the liver stiffness
measurement (r = 0.68, P < .001). The median blood loss during transection per
unit area was 4.1 mL/cm2 (range: 0.1-37.0 mL/cm2), and the frequency of major
complications was 16.0%. The liver stiffness measurement was the only independent
prognostic factor for both blood loss (regression coefficient: 1.14, 95%
confidence interval: 0.45-1.83, P = .001) and major complications (odds ratio:
2.14, 95% confidence interval: 1.63-2.93, P < .001). Receiver operating
characteristic curve analysis indicated a significant correlation between the
liver stiffness measurement and major complications with calculated area under
the curve of 0.81 (P < .001), and the sensitivity and specificity for prediction
of major complications (cutoff value: 5.3 kPa) were 64.3% and 87.8%,
respectively. On the other hand, the amount of blood loss was significantly
correlated with the frequency of major complications (P = .003). CONCLUSION: The
liver stiffness measurement by magnetic resonance elastography could be used as a
predictive marker for the risk of major complications due to blood loss during
liver resection.
PMID- 28411866
TI - Addressing the challenges of sleeve gastrectomy in end-stage renal disease:
Analysis of 100 consecutive renal failure patients.
AB - BACKGROUND: While previous studies have demonstrated short-term efficacy of
laparoscopic sleeve gastrectomy in candidates awaiting renal transplantation, the
combination of morbid obesity and end-stage renal disease presents unique
challenges to perioperative care. We demonstrate how increasing experience and
the development of postoperative care guidelines can improve outcomes in this
high-risk population. METHODS: Single-center medical records were reviewed for
renal transplantation candidates undergoing laparoscopic sleeve gastrectomy
between 2011 and 2015 by a single surgeon. Postoperative care protocols were
established and continually refined throughout the study period, including a
multidisciplinary approach to inpatient management and hospital discharge
planning. The first 100 laparoscopic sleeve gastrectomy patients were included
and divided into 4 equal cohorts based on case sequence. RESULTS: Compared with
the first 25 patients undergoing laparoscopic sleeve gastrectomy, the last 25
patients had shorter operative times (97.8 +/- 27.9 min vs 124.2 +/- 33.6 min),
lower estimated blood loss (6.6 +/- 20.8 mL vs 34.0 +/- 38.1 mL), and shorter
hospital duration of stay (1.7 +/- 2.1 days vs 2.9 +/- 0.7 days) (P < .01 each).
Readmission rates, complications, and 1-year mortality did not differ
significantly. CONCLUSION: Increasing experience and the development of clinical
care guidelines in this high-risk population is associated with reduced health
care resource utilization and improved perioperative outcomes.
PMID- 28411867
TI - A rapid approach for measuring silver nanoparticle concentration and dissolution
in seawater by UV-Vis.
AB - Detection and quantification of engineered nanoparticles (NPs) in environmental
systems is challenging and requires sophisticated analytical equipment.
Furthermore, dissolution is an important environmental transformation process for
silver nanoparticles (AgNPs) which affects the size, speciation and concentration
of AgNPs in natural water systems. Herein, we present a simple approach for the
detection, quantification and measurement of dissolution of PVP-coated AgNPs (PVP
AgNPs) based on monitoring their optical properties (extinction spectra) using UV
vis spectroscopy. The dependence of PVP-AgNPs extinction coefficient (E) and
maximum absorbance wavelength (lambdamax) on NP size was experimentally
determined. The concentration, size, and extinction spectra of PVP-AgNPs were
characterized during dissolution in 30ppt synthetic seawater. AgNPs concentration
was determined as the difference between the total and dissolved Ag
concentrations measured by inductively coupled plasma-mass spectroscopy (ICP-MS);
extinction spectra of PVP-AgNPs were monitored by UV-vis; and size evolution was
monitored by atomic force microscopy (AFM) over a period of 96h. Empirical
equations for the dependence of maximum absorbance wavelength (lambdamax) and
extinction coefficient (E) on NP size were derived. These empirical formulas were
then used to calculate the size and concentration of PVP-AgNPs, and dissolved Ag
concentration released from PVP-AgNPs in synthetic seawater at variable particle
concentrations (i.e. 25-1500MUgL-1) and in natural seawater at particle
concentration of 100MUgL-1. These results suggest that UV-vis can be used as an
easy and quick approach for detection and quantification (size and concentration)
of sterically stabilized PVP-AgNPs from their extinction spectra. This approach
can also be used to monitor the release of Ag from PVP-AgNPs and the concurrent
NP size change. Finally, in seawater, AgNPs dissolve faster and to a higher
extent with the decrease in NP concentration toward environmentally relevant
concentrations.
PMID- 28411868
TI - High resolution stream water quality assessment in the Vancouver, British
Columbia region: a citizen science study.
AB - Changing land cover and climate regimes modify water quantity and quality in
natural stream systems. In regions undergoing rapid change, it is difficult to
effectively monitor and quantify these impacts at local to regional scales. In
Vancouver, British Columbia, one of the most rapidly urbanizing areas in Canada,
750 measurements were taken from a total of 81 unique sampling sites representing
49 streams located in urban, forest, and agricultural-dominant watersheds at a
frequency of up to 12 times per year between 2013 and 2016. Dissolved nitrate
(NO3-N) and phosphate (PO4-P) concentrations, turbidity, water temperature, pH
and conductivity were measured by citizen scientists in addition to observations
of hydrology, vegetation, land use, and visible stream impacts. Land cover was
mapped at a 15-m resolution using Landsat 8 OLI imagery and used to determine
dominant land cover for each watershed in which a sample was recorded. Regional,
seasonal, and catchment-type trends in measurements were determined using
statistical analyses. The relationships of nutrients to land cover varied
seasonally and on a catchment-type basis. Nitrate showed seasonal highs in winter
and lows in summer, though phosphate had less seasonal variation. Overall,
nitrate concentrations were positively associated to agriculture and deciduous
forest and negatively associated with coniferous forest. In contrast, phosphate
concentrations were positively associated with agricultural, deciduous forest,
and disturbed land cover and negatively associated with urban land cover. Both
urban and agricultural land cover were significantly associated with an increase
in water conductivity. Increased forest land cover was associated with better
water quality, including lower turbidity, conductivity, and water temperature.
This study showed the importance of high resolution sampling in understanding
seasonal and spatial dynamics of stream water quality, made possible with the
large number of measurements taken with the help of trained volunteers. The
results underscore the value of citizen science in freshwater research.
PMID- 28411870
TI - The presence of coronary artery lesions may indicate the severity of the
inflammation rather than the cause.
PMID- 28411869
TI - Detection of endocrine disrupting chemicals and evidence of their effects on the
HPG axis of the European anchovy Engraulis encrasicolus.
AB - Natural/synthetic Endocrine Disrupting Chemicals (EDCs) may display estrogenic
activity and a lower potency than 17beta-estradiol. Nonetheless, their
concentrations and additive effects can affect the endocrine system and
reproductive processes related to the Hypothalamic-Pituitary-Gonadal (HPG) axis.
Because of their persistence in both the environment and biological systems, they
ultimately target multi-level predators, including humans. We detected presence
and effects of xenobiotics on wild anchovy Engraulis encrasicolus in the Western
Adriatic Sea. Twenty-one PCBs and five organochlorines were detected on the order
of ng g-1; vitellogenin, vitellogenin receptor and genes encoding for the zona
radiata proteins were evaluated in gonad and/or liver and found transcribed in
male specimens; in addition, intersex was histologically identified in the 13% of
testis. Our results have developed the understanding of the European anchovy's
reproductive toxicological risk and our approach could assist the comprehension
of the complex dynamics of commercially relevant Teleost species.
PMID- 28411871
TI - Targeting interleukin 23 for Crohn's disease: finding the right drug for the
right patient.
PMID- 28411872
TI - Induction therapy with the selective interleukin-23 inhibitor risankizumab in
patients with moderate-to-severe Crohn's disease: a randomised, double-blind,
placebo-controlled phase 2 study.
AB - BACKGROUND: The interleukin-23 pathway is implicated genetically and biologically
in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and
safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a
humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in
patients with moderately-to-severely active Crohn's disease. METHODS: In this
randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients
at 36 referral sites in North America, Europe, and southeast Asia. Eligible
patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least
3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as
a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the
ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity
(CDEIS) of at least 7 (>=4 for patients with isolated ileitis) on ileocolonoscopy
scored by a masked central reader. Patients were randomised 1:1:1 using an
interactive response system to a double-blind investigational product, and
stratified by previous exposure to TNF antagonists (yes vs no). Patients received
intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4,
and 8. The primary outcome was clinical remission (CDAI <150) at week 12
(intention-to-treat population). Safety was assessed in patients who received at
least one dose of study drug. This study is registered with ClinicalTrials.gov,
number NCT02031276. FINDINGS: Between March, 2014, and September, 2015, 213
patients were screened, and 121 patients randomised. At baseline, 113 patients
(93%) had been previously treated with at least one tumour necrosis factor (TNF)
antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82
risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg
arms) had clinical remission versus six (15%) of 39 placebo patients (difference
vs placebo 15.0%, 95% CI 0.1 to 30.1; p=0.0489). Ten (24%) of 41 patients who
received 200 mg risankizumab had clinical remission (9.0%, -8.3 to 26.2; p=0.31)
and 15 (37%) of 41 who received the 600 mg dose (20.9%, 2.6 to 39.2; p=0.0252).
95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to
200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse
events (nine, six, three); 12 discontinued (six, five, one); 24 had serious
adverse events (12, nine, three). The most common adverse event was nausea and
most common serious adverse event was worsening of underlying Crohn's disease. No
deaths occurred. INTERPRETATION: In this short-term study, risankizumab was more
effective than placebo for inducing clinical remission in patients with active
Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition
of p19 might be a viable therapeutic approach in Crohn's disease. FUNDING:
Boehringer Ingelheim.
PMID- 28411873
TI - [Survey adaptation for bio-behavioural surveillance of HIV in Chilean female sex
workers].
AB - OBJECTIVE: To adapt a behavioural questionnaire for second-generation HIV/AIDS
surveillance in female sex workers (FSWs) in the Metropolitan Region, Chile.
METHODS: Qualitative study of instruments validation. A Spanish instrument
adapted in Catalonia was validated through a translation and back-translation of
the original version. The content validity was determined through a modified
Delphi method, via FSW and HIV experts representing community, political and
institutional levels. Applicability aspects were determined by the application of
the questionnaire to FSW in the Metropolitan Region. RESULTS: The questionnaire,
drafted in Spain, was successfully adapted to Chilean Spanish. The content
validity process enabled sections to be created that address HIV in FSWs. The
adapted questionnaire takes less than 15minutes to complete, which makes it
usable in fieldwork. The 61 women surveyed came from different countries (all
were Latin Americans) and had different educational levels; all this enabled
potential applicability problems to be detected. DISCUSSION: The adapted
questionnaire for Chile contains all the UNAIDS indicators for FSWs, as well as
the recommended indicators of Family Health International for bio-behavioural
surveillance. Said questionnaire serves as a tool for second-generation HIV/other
STD surveillance and further contributes to preventive policies in Chilean FSWs.
PMID- 28411874
TI - [Association between radiation from mobile phones and tumour risk in adults].
AB - OBJECTIVE: To synthesize and analyse systematic reviews, case-control studies,
cohort studies and meta-analysis that investigate the association between
exposure to radiofrequency from mobile phones and the appearance of tumours in
adults. METHODS: A systematic search was conducted in Scopus, Web of Science, The
Cochrane Library, Medline and Cinahl of articles published in English and Spanish
between January 2005 and February 2016 that analyse the risk of tumour associated
with exposure to radiofrequency from mobile phones in adults. The recommendations
of the PRISMA Declaration were followed, and the quality of the articles was
analysed with the AMSTAR tool and the Newcastle-Ottawa Scale. RESULTS: 1034
studies were found, fourteen of which were included. Most studies agree that it
is not possible to determine a relationship in the short term, although long-term
(over 10 years) radiofrequency emitted by mobile phones can cause tumour effects,
with an increased risk by ipsilateral exposure and latency. CONCLUSIONS: Although
radiofrequency from mobile phones has tumour effects on humans, the available
scientific evidence is not robust. More rigorous follow-up studies with larger
sample sizes and broader periods are necessary to learn more about the long-term
effects.
PMID- 28411875
TI - Association between lateral patellar osteoarthrosis and knee morphology and
alignment in young adults.
AB - AIM: To assess whether patellar and trochlea morphology and patellar alignment
are associated with lateral patellar osteoarthrosis/chondrosis (OAC) in young
adults. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) images of 183
subjects (81 cases, 102 controls) aged 21-35 years of age were evaluated.
Quantitative measurements of patella and trochlea morphology and patellar
alignment were obtained. Axial and sagittal MRI images were reviewed to grade the
severity of focal cartilage defects along the lateral facet of the patella.
Controls had knees without any abnormalities and were compared to cases with mild
and severe lateral patellar OAC. Multivariable logistic regression was used to
assess associations between measurements and lateral patellar OAC adjusting for
body mass index. RESULTS: Cases were more likely to have higher Insall-Salvati
ratios (OR=350; p<0.001), shorter ratios of the medial to lateral facets of the
patella (OR=1.63*10-3; p<0.001), a shallower (angle closer to 180 degrees )
median eminence of the patella (OR=1.063; p=0.009), decreased trochlear cartilage
overlap with the patellar cartilage (OR=0.086; p=0.023), and a less angulated
lateral patellofemoral angle (OR=0.903; p=0.028), compared to controls. Cases
were also more likely to have patellar tendinosis (OR=5.265; p=0.045) and oedema
in the superolateral aspect of Hoffa's fat pad (OR=9.872; p<0.001). CONCLUSION:
Patellar and trochlear morphology and patellar alignment are associated with
lateral patellofemoral compartment OAC in young adults.
PMID- 28411876
TI - Stakeholders' Perceptions of Care Coordination: A Participatory Process.
AB - OBJECTIVE: Children with special health care needs or chronic conditions are more
likely to have unmet health needs than other children. The purpose of this study
was to use a community engagement research strategy to assess the essential
elements of care coordination that can serve as the foundation for a system-wide
care coordination model for children with special health care needs. STUDY
DESIGN: As part of a summit designed to review the status of pediatric care
coordination within the state of Arizona and a call to action, a qualitative
descriptive study was conducted to solicit anonymous feedback from 104
stakeholders (family, health care provider, or community entity) on the strengths
and areas of improvement in the current system that provides care to Arizona
children with special health care needs. Data were analyzed using inductive
content analysis. RESULTS: Five essential categories crucial to building an
effective and seamless care coordination model were extracted from the data:
Communication, Insurance, Health Care Capacity, Provider Knowledge, and Family
Education. CONCLUSIONS: The results from this study can serve as the working
foundation to build a system-wide model for pediatric care coordination
throughout the state. Providing care coordination services involves many
activities across a wide range of organizations and locations. Research that is
inclusive of community stakeholders can determine essential components for
building a foundation for care coordination.
PMID- 28411877
TI - Combined resection and radiofrequency ablation versus transarterial embolization
for intermediate-stage hepatocellular carcinoma: A propensity score matching
study.
AB - BACKGROUND/PURPOSE: This study aimed to compare the outcomes of combined hepatic
resection (HR) plus intraoperative radiofrequency ablation (RFA) and
transarterial embolization (TAE) for Barcelona Clinic Liver Cancer (BCLC) stage B
hepatocellular carcinoma (HCC) in case-controlled patient groups using the
propensity score. METHODS: A total of 179 patients with multifocal HCC treated
with HR plus RFA (n = 26) or TAE (n = 153) were retrospectively studied. All
patients were classified as BCLC stage B and Child-Pugh class A. Analyses were
performed over all participants as well as for propensity score-matched (1:3)
patients to adjust for baseline differences. Cumulative overall survival (OS) and
time to progression (TTP) were compared between the two groups using the Kaplan
Meier method, and independent predictors were identified by multivariate Cox
regression analysis. RESULTS: Patients treated with HR plus RFA had better OS and
longer TTP than those with TAE (p = 0.011 and p < 0.001, respectively).
Multivariate Cox regression analysis showed that combined therapy (hazard ratio
0.31; 95% confidence interval (CI), 0.12-0.78; p = 0.013), BCLC substage B2
(hazard ratio 1.82; 95% CI, 1.13-2.92; p = 0.013) and alpha-fetoprotein >= 400
ng/ml (hazard ratio 1.85; 95% CI, 1.12-3.05; p = 0.016) were independent factors
associated with OS. After propensity score matching, combined therapy was the
significant factor associated with OS and TTP by univariate and multivariate
analyses. CONCLUSION: Combined HR plus RFA may provide survival advantage
compared to TAE in patients with BCLC stage B HCC.
PMID- 28411878
TI - Food for thought: Autophagy researcher wins 2016 Nobel Prize in Physiology or
Medicine.
AB - This special edition of the Biomedical Journal honors the awarding of the 2016
Nobel Prize in Physiology and Medicine to Yoshinori Ohsumi for his pioneering
work on elucidating the mechanisms of autophagy. We also highlight a study
reporting a new and simple animal model for a widespread surgical technique
called interbody spinal fusion. Finally, this issue also includes two articles
reporting protocols that could produce specific cell types for cell based
therapies.
PMID- 28411879
TI - Apicomplexan autophagy and modulation of autophagy in parasite-infected host
cells.
AB - Apicomplexan parasites are responsible for a number of important human
pathologies. Obviously, as Eukaryotes they share a number of cellular features
and pathways with their respective host cells. One of them is autophagy, a
process involved in the degradation of the cell's own components. These
intracellular parasites nonetheless seem to present a number of original features
compared to their very evolutionarily distant host cells. In mammals and other
metazoans, autophagy has been identified as an important contributor to the
defence against microbial pathogens. Thus, host autophagy also likely plays a key
role in the control of apicomplexan parasites, although its potential
manipulation and subversion by intracellular parasites creates a complex
interplay in the regulation of host and parasite autophagy. In this mini-review,
we summarise current knowledge on autophagy in both parasites and their host
cells, in the context of infection by three Apicomplexa: Plasmodium, Toxoplasma,
and Theileria.
PMID- 28411880
TI - In vitro induction effect of 1,25(OH)2D3 on differentiation of hair follicle stem
cell into keratinocyte.
AB - BACKGROUND: Stem cells are characterized by self-renewal and differentiation
capabilities. The bulge hair follicle stem cells (HFSCs) are able to convert to
epithelial components. The active metabolite of vitamin D, 1,25(OH)2D3, plays
important roles in this differentiation process. In the present study has found
that 1,25(OH)2D3 induces the HFSCs differentiation into keratinocyte. METHODS:
HFSCs are isolated from rat whiskers and cultivated in DMEM medium. To isolate
bulge stem cell population, flow cytometry and immunocytochemistry using K15,
CD34 and nestin biomarkers were performed. In order to accelerate the HFSCs
differentiation into eratinocyte, HFSCs were treated with 10-12 M, 1,25(OH)2D3
every 48 h for a week. RESULTS: Immunocytochemistry results showed that bulge
stem cells are nestin and CD34 positive but K15 negative before differentiation.
Subsequently flow cytometry results, showed that the expression of nestin, CD34
and K15 were 70.96%, 93.03% and 6.88% respectively. After differentiation, the
immunocytochemical and flow cytometry results indicated that differentiated cells
have positive reaction to K15 with 68.94% expression level. CONCLUSION: It was
concluded that 10-12 M, 1,25(OH)2D3 could induce the HFSCs differentiation into
keratinocytes.
PMID- 28411881
TI - Overexpression of MutL homolog 1 and MutS homolog 2 proteins have reversed
prognostic implications for stage I-II colon cancer patients.
AB - BACKGROUND: The outcome of colon cancer patients without lymph node metastasis is
heterogeneous. Searching for new prognostic markers is warranted. METHODS: One
hundred twenty stage I-II colon cancer patients who received complete surgical
excision during 1995-2004 were selected for this biomarker study.
Immunohistochemical method was used to assess p53, epidermal growth factor
receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing.
RESULTS: Thirty three patients (27.5%) developed metachronous metastasis during
follow up. By multivariate analysis, only female gender (p = 0.03), high serum
carcinoembryonic antigen (CEA) level (?5 ng/ml) (p = 0.04), and MLH1
overexpression (p = 0.003) were associated with the metastasis group. The 5-year
survival rate were also significantly lower for female gender (71.7% versus
88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1
overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression
was associated with better survival, 95.1% versus 75.5% (p = 0.024). CONCLUSIONS:
The reversed prognostic implications in the overexpression of MLH1 and MSH2 for
stage I-II colon cancer patients is a novel finding and worthy of further
confirmation.
PMID- 28411882
TI - In-vitro generation of interleukin-10 secreting B-regulatory cells from donor
adipose tissue derived mesenchymal stem cells and recipient peripheral blood
mononuclear cells for potential cell therapy.
AB - BACKGROUND: Interleukin-10 secreting B-cells are a major subset of B-regulatory
cells (B-regs), commonly recognized as CD19+/38hi/24hi/IL10+. They carry out
immunomodulation by release of specific cytokines and/or cell-to-cell contact. We
have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem
cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear
cells (PBMC) for potential cell therapy. MATERIAL AND METHODS: Mononuclear cells
separated by density gradient centrifugation from 50 ml anti-coagulated blood of
15-RAR and respective donors were analysed for baseline B-regs using appropriate
antibodies. Equal amount (20 * 106 cells/ml) of stimulator (irradiated at 7.45
Gy/min for 10 min) and responder (non-irradiated) cells were co-cultured with in
vitro generated AD-MSC (1 * 106 cells/ml) in proliferation medium containing
lipopolysaccharide from E. coli K12 strain at 37 degrees C with 5% CO2. Cells
were harvested on day-7 and analyzed for viability, sterility, quantity,
morphology and phenotyping. In-vitro generated B-reg levels were compared with
baseline B-regs. RESULTS: In-vitro generated B-reg count increased to 16.75% from
baseline count of 3.35%. CONCLUSION: B-regs can be successfully generated in
vitro from donor AD-MSC and RAR PBMC for potential cell therapy.
PMID- 28411883
TI - Horning cell self-digestion: Autophagy wins the 2016 Nobel Prize in Physiology or
Medicine.
AB - Autophagy is an evolutionarily conserved process by which eukaryotic cells
eliminate intracellular components via the lysosomal degradation process. This
cell self-digestion process was first discovered and morphologically
characterized in the late 1950s and early 1960s. The genetic screen studies in
baker's yeast in the 1990s further identified the essential genes functioning in
the autophagic process. In the past two decades, the detailed molecular process
involved in the completion of autophagy was delineated. Additionally, autophagy
has been implied to function in many aspects of biological processes, including
maintenance of organelle integrity, protein quality control, regulation of the
stress response, and immunity. In addition to maintain cell homeostasis,
autophagy has recently been shown to be modulated and to participate in the
pathogenesis of human diseases, such as pathogen infections, neurodegenerative
diseases, and tumor development. Overall, the breakthrough in autophagy research
relies on the discovery of autophagy-related genes (ATGs) using a genetic
screening approach in Saccharomyces cerevisiae, which was established by
Yoshinori Ohsumi. This year the Nobel Committee has awarded Yoshinori Ohsumi the
Nobel Prize in Physiology or Medicine for his remarkable contribution to
autophagy research.
PMID- 28411884
TI - Risk factors for relapse of resectable pathologic N2 non small lung cancer and
prediction model for time-to-progression.
AB - BACKGROUND: Pathologic N2 non-small-cell lung cancer (NSCLC) was demonstrated
with poor survival among literature. In this study, we retrospectively reviewed
patients with pathologic N2 NSCLC and received anatomic resection (i.e.
lobectomy) for further relapse risk factor analysis. The aim of this study is to
identify the clinicopathologic factors related to relapse among resectable N2
NSCLC patients and to help clinicians in developing individualized follow up
program and treatment plan. METHOD: From January 2005 to July 2012, 90 diagnosed
pathologic N2 NSCLC patients were enrolled into this study. We retrospectively
reviewed medical records, image studies, and pathology reports to collect the
patient clinico-pathologic factors. RESULT: We identified that patients with
visceral pleural invasion (p = 0.001) and skip metastases along mediastinal lymph
node (p = 0.01) had a significant relationship to distant and disseminated
metastases. Patients who had 2 or more risk factors for relapse demonstrated poor
disease free survival than those who had less than 2 risk factors (p = 0.02). The
number of involved metastatic area were significantly influential to the period
of time-to-progression. The duration of time-to-progression was correlated with
square of number of involved metastatic areas. (Pearson correlation coefficient =
-0.29; p = 0.036). CONCLUSION: Relapse risk factors of resectable pathologic N2
NSCLC patient after anatomic resection were visceral pleural invasion, skip
mediastinal lymph node involvement, and the receipt of neoadjuvant therapy. The
duration of time-to-progression was correlated with square of number of involved
metastatic areas.
PMID- 28411885
TI - Characterization of a novel caudal vertebral interbody fusion in a rat tail
model: An implication for future material and mechanical testing.
AB - BACKGROUND: Of the proposed animal interbody fusion models, rat caudal discs have
gained popularity in disc research due to their strong resemblance to human discs
with respect to geometry, composition and mechanical properties. The purpose of
this study is to demonstrate an efficient, repeatable and easily accessible
animal model of interbody fusion for future research into mechanical testing and
graft materials. METHODS: Twelve 12-week-old female Sprague-Dawley (SD) rats
underwent caudal interbody fusion of the third and fourth coccygeal vertebrae of
the tail. Serial radiological evaluation, and histological evaluation and manual
palpation after sacrifice were performed to assess the fusion quality. Mechanical
testing of functional units (FUs) of non-operated and operated segments was
compared using a three-point bending test. RESULTS: At postoperative 12 weeks,
callus formation was observed at the fusion sites in all rats, with the mean
radiological evaluations of 2.75/3 according to the Bransford classification.
Newly formed bone tissue was also observed in all rats with the mean histological
score of 5.85/7, according to the Emery grading system. No palpable gaps and
obvious change of bending stiffness was observed in the operated segments. The
mean bending stiffness of the FUs was statistically higher than that of the
control FUs (26.57 +/- 6.71 N/mm vs. 12.45 +/- 3.21 N/mm, p < 0.01). CONCLUSION:
The rat caudal disc interbody fusion model proved to be an efficient, repeatable
and easily accessible model. Future research into adjuvant treatments like growth
factor injection and alternative fusion materials under conditions of
osteoporosis using this model would be worthwhile.
PMID- 28411886
TI - Interference factors regarding the path of insertion of rotational-path removable
partial dentures.
AB - BACKGROUND: The aims of this study were to evaluate the effect of the location of
the rotational center and the morphology of teeth resulting in interference with
the rotational path of insertion and to estimate when an interference test should
be performed. METHODS: A total of 400 dental radiograms of maxillary and
mandibular first and second molars (100 for each position) were selected. The
radiograms were used to hand-sketch the outlines on tracing paper. Then, an
interference test was simulated using calipers. Mesial long occlusal rest seats
with three different lengths were designed. A curve-simulated rotational path was
drawn on the tracing paper showing the outline of a molar. If the curve was
intersected by the mesial outline, interference was occurred. A total of 1200
tests were performed. RESULTS: A significant number of interference cases (18.5%,
N = 400) occurred when the rotational center was placed at the most distal margin
of the occlusal surface. The interference was reduced (2.75%, N = 400) but still
present at the distal fourth of the occlusal surface. At the distal one-third of
the occlusal surface, interference did not occur (0%, N = 400). There was a
significant difference between the results of the three rotational centers (p <
0.0001). CONCLUSIONS: The interference test was not required for a rotational
center at the distal third to half of the occlusal surface. However, if the
length of the long occlusal rest extends beyond the distal third, an interference
test is recommended before final impression.
PMID- 28411889
TI - Factibility and security study of the PICS-AFTM plug for the treatment of
cryptoglandular anal fistula.
AB - INTRODUCTION: The PICS-AFTM (Curaseal Inc.) device is a new plug made of collagen
that has a retention system in the internal orifice. This pilot study was
designed to assess both the feasibility and safety of this plug in the treatment
of trans-sphincteric anal fistulas. METHODS: A total of 44 patients (34 men),
with a mean age of 54.68+/-7.3, with trans-sphincteric anal fistulas were
included in the study; 34 of them were analyzed. All patients were examined
according to a strict preoperative protocol and until 6 months after surgery. The
feasibility of the procedure and the adverse events were analyzed. RESULTS:
Finally, 34 patients were operated on, and in 30 of them the plug was used.
Therefore, the feasibility was calculated at 88%. There was a total of 16 adverse
events, 4recorded as not related (3 mild and one moderate) and 12 related to the
procedure or to the device implanted. Of these, 5were mild, 5moderate and
2severe. The majority of the events reported were related to proctalgia (4
patients) or infection at the implant site (4 patients). CONCLUSIONS: The present
study indicates that the new collagen plug can be placed effectively and with an
acceptable complication rate.
PMID- 28411888
TI - Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0
rectal tumors. Local recurrence, complete clinical and pathological response.
AB - INTRODUCTION: The association of preoperative chemoradiotherapy and transanal
endoscopic surgery in T2 and superficial T3 rectal cancers presents promising
results in selected patients. The main objective is to evaluate the long-term
loco-regional and systemic recurrence and, as secondary objectives, to provide
results of postoperative morbidity and the correlation between complete clinical
and pathological response. METHODS: This is a retrospective observational study
including a consecutive series of patients with T2-T3 superficial rectal cancer,
N0, M0 who refused radical surgery (2008-2016). The treatment consisted of
preoperative chemotherapy (5-fluorouracil or capecitabine) combined with
radiotherapy (50, 4Gy) and transanal endoscopic surgery after 8weeks.
Preoperative, surgical, pathological and long-term oncologic results were
analyzed. RESULTS: Twenty-four patients were included in the study. Two of them
required rescue radical surgery for unfavorable pathological results. A local
recurrence (4.5%) was observed and 2patients presented systemic recurrence (9%),
with a median follow-up of 45 months. A complete clinical tumor response was
achieved in 12 patients (50%), and complete pathological tumor response in 9
patients (37.5%). Postoperative complications were observed in 5 patients
(20.8%), and they were mild except one. There was no postoperative mortality.
CONCLUSIONS: In this stage of rectal cancer, our results seem to support this
strategy, mainly when a complete pathological response is achieved. The complete
clinical tumor response does not coincide with the pathological tumor response.
Randomized prospective studies should be performed to standardize this treatment.
PMID- 28411890
TI - Time to rethink transanal endoscopic microsurgery for rectal cancer after
neoadjuvant chemoradiation for highly selected patients.
PMID- 28411887
TI - From Christian de Duve to Yoshinori Ohsumi: More to autophagy than just dining at
home.
AB - Christian de Duve first coined the expression "autophagy" during his seminal work
on the discovery of lysosomes, which led to him being awarded the Nobel Prize in
Physiology or Medicine in 1974. The term was adopted to distinguish degradation
of intracellular components from the uptake and degradation of extracellular
substances that he called "heterophagy". Studies until the 1990s were largely
observational/morphological-based until in 1993 Yoshinori Oshumi described a
genetic screen in yeast undergoing nitrogen deprivation that led to the isolation
of autophagy-defective mutants now better known as ATG (AuTophaGy-related) genes.
The screen identified mutants that fell into 15 complementation groups implying
that at least 15 genes were involved in the regulation of autophagy in yeast
undergoing nutrient deprivation, but today, 41 yeast ATG genes have been
described and many (though not all) have orthologues in humans. Attempts to
identify the genetic basis of autophagy led to an explosion in its research and
it's not surprising that in 2016 Yoshinori Oshumi was awarded the Nobel Prize in
Physiology or Medicine. Our aim here is not to exhaustively review the ever
expanding autophagy literature (>60 papers per week), but to celebrate Yoshinori
Oshumi's Nobel Prize by highlighting just a few aspects that are not normally
extensively covered. In an accompanying mini-review we address the role of
autophagy in early-diverging eukaryote parasites that like yeast, lack lysosomes
and so use a digestive vacuole to degrade autophagosome cargo and also discuss
how parasitized host cells react to infection by subverting regulation of
autophagy.
PMID- 28411891
TI - Recombinant expression of Thermobifida fusca E7 LPMO in Pichia pastoris and
Escherichia coli and their functional characterization.
AB - The discovery of lytic polysaccharides monooxygenases copper dependent (LPMOs)
revolutionized the classical concept that the cleavage of cellulose is a
hydrolytic process in recent years. These enzymes carry out oxidative cleavage of
cellulose (and other polysaccharides), acting synergistically with cellulases and
other hydrolases. In fact, LPMOs have the potential for increasing the efficiency
of the lignocellulosic biomass conversion in biofuels and high value chemicals.
Among a small number of microbial LPMOs that have been characterized, some LPMOs
were expressed and characterized biochemically from the bacteria Thermobifida
fusca, using the host Escherichia coli. In this work, the E7 LPMO protein of T.
fusca was expressed both in E. coli (native DNA sequence) and Pichia pastoris
(codon-optimized DNA sequence), for further analysis of oxidative cleavage, with
PASC (phosphoric acid swollen cellulose) and Avicel PH-101 substrates, using mass
spectrometry analysis. Mass spectra results of Avicel PH-101 and PASC cleavages
by purified E7 LPMO expressed in E. coli and in P. pastoris allowed the
visualization of compounds corresponding to oxidized and non-oxidized
oligosaccharides. Further optimization of reactions will be performed, since it
was found only one degree of polymerization (DP 7). This work demonstrated that
it is possible to produce the E7 LPMO from T. fusca in the host P. pastoris, and
the recombinant protein was shown to be active on cellulose. The approach used in
the present work could be an alternative to produce this bacterial LPMO for
cellulose cleavage.
PMID- 28411892
TI - Advanced penile cancer with iliac lymph node involvement treated with radiation
and concurrent gemcitabine.
AB - Penile cancer is a rare entity with only 2000 new cases a year in the United
States. Even though early stage penile cancer has an excellent prognosis,
patients with positive pelvic lymph nodes have an overall 5-year survival rate
under 10%. There is no consensus for the management of pelvic node-positive
patients, although most guidelines are in favour of pelvic lymph node dissection
for patients with two or more positive nodes, followed by adjuvant chemotherapy.
We describe here the case of a patient with numerous metastatic lymph nodes at
diagnosis, treated with chemoradiation (66Gy with concurrent gemcitabine) after
failure of first-line chemotherapy and still alive and disease-free 7 years after
diagnosis.
PMID- 28411893
TI - Genomic Approaches to Hypertension.
AB - Genomic insights and analyses of Mendelian hypertension (HTN) syndromes and
Genome-Wide Association study (GWAS) on essential hypertension have contributed
to the depth of understanding of the genetics origins of hypertension. Mendelian
syndromes are important for the field, since such knowledge leads to specific
insights about disease pathogenesis and the potential for precision medicine. The
clinical impact of findings of on essential hypertension is continuously
evolving, and the insights accrued will refine efforts to combat the societal
impact of hypertension. Comprehensive identification of all genomic variants of
hypertension, along with their individual associated mechanisms, is paving the
way forward in the era of personalized medicine. The overriding challenge for
care providers is to reduce health inequities through improved compliance and,
perhaps, new paradigms for implementation science that incorporate genomic
medicine.
PMID- 28411894
TI - The Effects of Dietary Factors on Blood Pressure.
AB - Evidence supports that multiple dietary factors affect blood pressure (BP).
Dietary changes that effectively lower BP are weight loss, reduced sodium intake,
increased potassium intake, moderation of alcohol intake, and Dietary Approaches
to Stop Hypertension-style and vegetarian dietary patterns. In view of the
increasing levels of BP in children and adults and the continuing epidemic of BP
related cardiovascular and renal diseases, efforts to reduce BP in both
nonhypertensive and hypertensive individuals are warranted. The challenge to
health care providers, researchers, government officials, and the general public
is developing and implementing clinical and public health strategies that lead to
sustained dietary changes.
PMID- 28411895
TI - The Environment and Blood Pressure.
AB - A host of environmental factors can significantly increase arterial blood
pressure (BP) including cold temperature, high altitude, loud noises, and ambient
air pollutants. Although brief exposures acutely elevate BP, over the long term,
chronic exposures may be capable of promoting the development of sustained
hypertension. Given their omnipresent nature, environmental factors may play a
role in worsening BP control and heightening overall cardiovascular risk at the
global public health level.
PMID- 28411897
TI - Management of Essential Hypertension.
AB - The treatment of essential hypertension is one of the most critical interventions
to decrease cardiovascular morbidity and mortality. The prevalence of
hypertension in the US varies across race/ethnicity with African Americans having
the highest prevalence and overall less control among racial/ethnic minorities
compared with non-Hispanic whites. Therapeutic lifestyle modifications are the
bedrock of essential hypertension control, but most patients with hypertension
will require pharmacotherapy, usually with multiple medications often in
combination. Overall, the principal drug classes recommended as initial
pharmacotherapy are thiazide-type diuretics, calcium channel blockers, and
angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
PMID- 28411896
TI - Psychosocial Factors and Hypertension: A Review of the Literature.
AB - Black people have the highest prevalence of hypertension in the United States.
Evidence suggests that psychosocial factors increase the risks for hypertension
and help to account for racial differences in this condition. This article
reviews research on psychosocial factors and hypertension, and contextualizes the
findings within a health disparities framework. A wide range of psychosocial
factors contribute to hypertension but understanding remains limited about how
these factors relate to each other and accumulate to contribute to hypertension
disparities. Future research on psychosocial factors and hypertension needs to
enhance the effectiveness of interventions to reduce hypertension risk in ethnic
minority communities.
PMID- 28411898
TI - Balancing Overscreening and Underdiagnosis in Secondary Hypertension: The Case of
Fibromuscular Dysplasia.
AB - Knowledge about fibromuscular dysplasia (FMD) has broadened over the last several
decades. It is no longer considered a rare and benign entity limited to renal
arteries and causing just hypertension. It affects other parts of the arterial
tree nearly as frequently as the renal arteries. Complications of undiagnosed and
untreated extrarenal FMD can be debilitating and life threatening. However, this
disease, specifically extrarenal FMD, is not well known to many physicians and
patients. Combined with the nonspecific symptoms and signs of the disease, this
leads to delayed diagnosis and missed opportunity to prevent serious vascular
complications.
PMID- 28411899
TI - Device-Directed Therapy for Resistant Hypertension.
AB - Hypertension remains a significant risk factor for an array of diseases despite
advancements in pharmacotherapy. Patients with resistant hypertension who do not
respond to conventional medical treatments and lifestyle modifications are
especially at risk for poor health outcomes. With the increasing awareness of
resistant hypertension, ever-evolving research efforts continue to focus on
innovative interventions, including renal denervation, median nerve stimulation,
and baroreceptor activation therapy. This article reviews the current evidence
and summarizes previous clinical trials for each of these interventions.
PMID- 28411900
TI - Contemporary Approaches to Patients with Heart Failure.
AB - Incident heart failure and the burden of hospitalization may be demonstrating a
decline. However, as the population ages, the prevalence of heart failure
continues to increase. Mortality among heart failure patients is increasingly due
to non-cardiovascular causes. Current evidence-based therapy for heart failure
has improved heart failure related mortality. Current efforts should be directed
toward optimizing evidence based medical and device therapy, reducing morbidity,
and increasing quality of life with heart failure. Future clinical trials should
focus on therapies for heart failure with preserved ejection fraction,
regenerative therapy for heart failure, and optimizing durable mechanical support
for end-stage heart failure.
PMID- 28411901
TI - The Role of Implantable Hemodynamic Monitors to Manage Heart Failure.
AB - Heart failure is associated with high rates of hospitalization and
rehospitalization, resulting in substantial clinical and economic burden. Current
approaches to monitoring patients with heart failure have done little to reduce
these high rates of heart failure hospitalization. Implantable hemodynamic
monitors have been developed to remotely provide direct measurement of
intracardiac and pulmonary artery pressures in ambulatory patients with heart
failure. These devices have the potential to direct day-to-day management of
patients with heart failure to reduce hospitalization rates. The use of a
pulmonary artery pressure measurement system has been shown to reduce the risk of
heart failure hospitalization in patients with systolic and diastolic heart
failure.
PMID- 28411902
TI - Contemporary Drug-Eluting Stent Platforms: Design, Safety, and Clinical Efficacy.
AB - First-generation drug-eluting stents significantly improved treatment of coronary
disease, decreasing rates of revascularization. This was offset by high rates of
late adverse events, driven primarily by stent thrombosis. Research and design
improvements of individual DES platform components led to next-generation devices
with superior clinical safety and efficacy profiles compared with bare-metal
stents and first-generation drug-eluting stents. These design improvements and
features are explored, and their resulting clinical safety and efficacy reviewed,
focusing on platforms approved by the Food and Drug Administration currently
widely used in the United States.
PMID- 28411903
TI - Left Atrial Appendage Closure Device in Atrial Fibrillation.
AB - The relationship of stroke and atrial fibrillation seems to become more complex
as we gain more knowledge of the issue. Recent studies have questioned the
temporal relationship between the two, which also questions causation. Left
atrial appendage closure is an attractive, but unproven technology when compared
with the 50-year experience with warfarin. In a patient who is on warfarin and
having no issues with bleeding, medication intolerance, or lack of efficacy, it
is difficult to justify stopping the drug and placing a closure device as sole
therapy to prevent a stroke.
PMID- 28411905
TI - FPIES: The dark side of food allergy.
PMID- 28411906
TI - Serum levels of adiponectin and leptin in asthmatic patients and its relation
with asthma severity, lung function and BMI.
AB - INTRODUCTION: Asthma is one of the diseases which has a high prevalence in
developed and developing countries. The relationship between asthma and obesity
has always been focused by researchers. In this field, adipokines, especially
adiponectin and leptin have highly attended by the scientist. The aim of this
study was to determine the serum level of adiponectin, leptin and the
leptin/adiponectin ratio in asthmatic patients and its relationship with disease
severity, lung function and BMI (body mass index). METHODS: In this cross
sectional study, 90 asthmatic women admitted to the tertiary referral hospital in
Kurdistan province - Iran, were examined. First, BMI was measured and then
pulmonary function tests were performed in all asthmatics patient. Forced
expiratory volume in 1s (FEV1), forced vital capacity (FVC), and FEV1/FVC, were
measured. At the end, blood samples were collected and serum level of adiponectin
and leptin were measured by ELISA method. RESULT: Serum leptin and
leptin/adiponectin levels correlated positively with asthma severity and BMI
(p=0.0001), but there was no correlation between adiponectin level with asthma
severity and BMI (p>0.05), also serum leptin and leptin/adiponectin levels
inversely correlated with FEV1 and FVC in patient (p=0.0001). CONCLUSION: Asthma
is linked with obesity, and there is an association between asthma severity and
BMI with serum leptin and leptin/adiponectin levels, but our results do not
support a significant role of adiponectin in obesity or asthma.
PMID- 28411908
TI - Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal
Mass.
AB - The management of patients with hereditary kidney cancers presents unique
challenges to clinicians. In addition to an earlier age of onset compared with
patients with sporadic kidney cancer, those with hereditary kidney cancer
syndromes often present with bilateral and/or multifocal renal tumors and are at
risk for multiple de novo lesions. This population of patients may also present
with extrarenal manifestations, which adds an additional layer of complexity.
Physicians who manage these patients should be familiar with the underlying
clinical characteristics of each hereditary kidney cancer syndrome and the
suggested surgical approaches and recommendations of genetic testing for at-risk
individuals.
PMID- 28411907
TI - Epidemiology of the Small Renal Mass and the Treatment Disconnect Phenomenon.
AB - The incidence of kidney cancer has steadily increased over recent decades, with
most new cases now found when lesions are asymptomatic and small. This downward
stage migration relates to the increasing use of abdominal imaging. Three public
health epidemics-smoking, hypertension, and obesity-also play roles in the
increase. Treatment mirrors the rise in incidence, with increasing interest in
nephron-sparing therapies. Despite earlier detection and increasing treatment,
the mortality rate has not decreased. This treatment disconnect phenomenon
highlights the need to decrease unnecessary treatment of indolent tumors and
address modifiable risk factors to reduce incidence and mortality.
PMID- 28411909
TI - Current Trends in Renal Surgery and Observation for Small Renal Masses.
AB - There has been a rising incidence of small renal masses and concomitant downward
stage migration. This has led to an evolution in the management of kidney cancer
from radical nephrectomy to nephron-sparing treatment options including
observation. The adoption of partial nephrectomy continues to increase but is
still incomplete leading to significant disparities in the delivery of care
throughout the country. Surgical excision remains the treatment of choice for
small kidney cancers; however, ablative therapies and active surveillance are
emerging as reasonable options for select patients. With continued refinements in
treatment options and improvements in ability to risk stratify SRMs, the current
treatment trends will likely continue to evolve.
PMID- 28411910
TI - Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.
AB - Anatomic tumor complexity can be objectively measured and reported using
nephrometry. Various scoring systems have been developed in an attempt to
correlate tumor complexity with intraoperative and postoperative outcomes.
Nephrometry may also predict tumor biology in a noninvasive, reproducible manner.
Other scoring systems can help predict surgical complexity and the likelihood of
complications, independent of tumor characteristics. The accumulated data in this
new field provide provocative evidence that objectifying anatomic complexity can
consolidate reporting mechanisms and improve metrics of comparisons. Further
prospective validation is needed to understand the full descriptive and
predictive ability of the various nephrometry scores.
PMID- 28411911
TI - Risk Assessment in Small Renal Masses: A Review Article.
AB - The incidence of localized renal cell carcinoma (RCC) has been steadily
increasing, in large part because of the increased use of imaging. Optimizing the
management of localized RCC has become one of the leading priorities and foremost
challenges within the urologic-oncologic community. Adequate risk stratification
of patients following the diagnosis of localized RCC has become meaningful in
deciding whether to treat, how to treat, and how intensively to treat. This
article characterizes the existing risk assessment models that can be useful as
treatment decision aids for patients with localized RCC.
PMID- 28411912
TI - Current Role of Renal Biopsy in Urologic Practice.
AB - Most small renal masses (SRMs) are indolent. In fact, only approximately 80% of
SRMs are malignant. Furthermore, SRMs are commonly detected in elderly and
comorbid patients. Therefore, opportunities for better care intensity calibration
exist. Renal mass biopsy (RMB), when appropriately used, is a valuable clinical
tool to help with critical clinical decision-making in patients with SRM. This
article summarizes the role of modern RMB in helping gauge care for patients with
SRM.
PMID- 28411913
TI - Active Surveillance for the Small Renal Mass: Growth Kinetics and Oncologic
Outcomes.
AB - Active surveillance for small renal masses (SRMs) is an accepted management
strategy for patients with prohibitive surgical risk. Emerging prospectively
collected data support the concept that a period of initial active surveillance
in an adherent patient population with well-defined criteria for delayed
intervention is safe. This article summarizes the literature describing growth
kinetics of SRMs managed initially with observation and oncologic outcomes for
patients managed with active surveillance. Existing clinical tools to determine
and contextualize competing risks to mortality are explored. Finally, current
prospective clinical trials with defined eligibility criteria, surveillance
schema, and triggers for delayed intervention are highlighted.
PMID- 28411914
TI - Ablative Therapy for Small Renal Masses.
AB - The management of small renal masses has become an important public health topic.
The increased use of cross-sectional imaging and ultrasound has led to a downward
stage migration for the detection of small renal masses. Cancer-specific
survival, however, has not reflected this trend accordingly. Although partial
nephrectomy has been the mainstay of treatment of small renal masses less than 4
cm, there is growing interest in ablative therapies, such as cryoablation and
radiofrequency ablation, due to decreased morbidity. Oncologic outcomes are
limited by methodology and length of follow-up, but short-term recurrence rates
are low.
PMID- 28411915
TI - Surgical Techniques in the Management of Small Renal Masses.
AB - This article provides a review and outline of the various surgical techniques for
small renal masses. It covers surgical approaches and compares outcomes of open
versus minimally invasive surgery. The article discusses renal nephrometry
scoring and renal ischemia at time of resection. Techniques for controlling the
renal hilum and controlling blood flow to the kidney are described. Extirpative
techniques for small renal masses are reviewed along with a comparison of
outcomes. With careful adherence to key oncologic and surgical principles,
negative margins, no complications, and no or minimal decline in renal functional
outcomes can be achieved.
PMID- 28411916
TI - Renal Ischemia and Functional Outcomes Following Partial Nephrectomy.
AB - Renal function after renal cancer surgery is a critical component of
survivorship. Quantity and quality of preserved parenchyma are the most important
determinants of functional recovery; type and duration of ischemia play secondary
roles. Several studies evaluated surgical techniques to minimize ischemia;
however, long-term outcomes and potential benefits over clamped partial
nephrectomy (PN) have not been consistently demonstrated. Analysis of acute
kidney injury (AKI) after PN suggest that most kidneys recover strongly even if
AKI is experienced after surgery. Ongoing study is required to evaluate long-term
implications of AKI after PN and further assess impact of ischemia on functional
outcomes.
PMID- 28411917
TI - Comparative Effectiveness of Surgical Treatments for Small Renal Masses.
AB - In the management of small renal masses (SRMs), treatment options include partial
nephrectomy (PN), radical nephrectomy (RN), ablation, renal biopsy, and active
surveillance. Large series retrospective and meta-analyses demonstrate PN may
confer greater preservation of renal function, overall survival, and equivalent
cancer control when compared with RN. As newer therapies emerge, we should
critically evaluate the risks and benefits associated with the surgical
management of SRMs among patients with competing comorbidities, complex tumors,
and high-risk disease. Among younger patients with SRMs amenable to resection,
optimization of postoperative patient health should be prioritized.
PMID- 28411918
TI - Lymph Node Dissection for Small Renal Masses.
AB - Because the majority of small renal masses (SRMs; <4 cm) demonstrate low
metastatic potential and can be effectively treated with radical or partial
nephrectomy, the role of lymph node dissection (LND) at the time of surgery is
unclear. A randomized trial demonstrated no survival benefit of LND in clinically
localized renal cell carcinoma. Thus, LND is not recommended routinely for SRMs.
For patients with high-risk features or radiographic evidence of lymphadenopathy,
however, LND may improve local staging and potentially provide a survival
benefit. If performed, a LND template should be based on the known lymphatic
drainage of the kidneys.
PMID- 28411919
TI - Complications of Renal Surgery.
AB - The incidence of the small renal mass continues to increase owing to the aging
population and the ubiquity imaging. Most of these tumors are stage I tumors.
Management strategies include surveillance, ablation, and extirpation. There is a
wide body of literature favoring nephron-sparing approaches. Although nephron
sparing surgery may yield decreased long-term morbidity, it is not without its
drawbacks, including a higher rate of complications. Urologists must be attuned
to the complications of surgery and develop strategies to minimize risk. This
article reviews expected complications of surgery on renal masses and risk
stratification schema.
PMID- 28411920
TI - Neoadjuvant Targeted Molecular Therapy Before Renal Surgery.
AB - Neoadjuvant targeted molecular therapy may benefit select patients with
metastatic renal cell carcinoma. The primary use of this therapy in patients with
metastatic disease is to reduce tumor burden, prevent distant metastasis, and
increase overall survival. Neoadjuvant therapy may reduce tumor size and tumor
complexity, facilitate partial nephrectomy rather than radical nephrectomy,
downstage tumor thrombus facilitating thrombectomy, and make unresectable tumors
resectable when applied to selected patients. These potential benefits of
neoadjuvant therapy require further clinical trials to better define the renal
function and oncological and survival outcomes in patients receiving each active
agent.
PMID- 28411921
TI - Salvage Surgery After Renal Mass Ablation.
AB - Thermal ablative techniques represent treatment options for patients with small
renal masses who are not candidates for surgery. The oncologic efficacy of
ablation has not been compared in a randomized fashion with nephron-sparing
surgery, and the urologist must be knowledgeable regarding the workup and
treatment of patients with suspected residual or recurrent tumor following these
therapies. Surveillance of patients with tumor recurrence after ablation may be
indicated in select circumstances. When patients are deemed appropriate for
salvage therapy, most undergo a repeat course of the same ablative modality.
Salvage surgery is possible but often complicated by the prior ablative
techniques.
PMID- 28411922
TI - Postoperative Surveillance for Renal Cell Carcinoma.
AB - Postoperative surveillance is an integral part of renal cell carcinoma (RCC)
care. However, evidence supporting the practice is lacking. RCC guidelines offer
disparate recommendations leading to variation in care. Recently, the
effectiveness of guidelines has been questioned and a debate has ignited over
whether current protocols merit optimization. Guidelines show limitations in RCC
risk assessment, protocol stratification, and definition of duration of follow
up. Alternative strategies have addressed some of these limitations, but further
analysis is warranted. Until challenges with assessing a survival benefit are
negotiated, efforts should be made to optimize and standardize guidelines and
learn of more tangible benefits to surveillance.
PMID- 28411923
TI - Erratum.
PMID- 28411924
TI - Small Renal Mass.
PMID- 28411925
TI - The Small Renal Mass and Its Management in Urologic Practice.
PMID- 28411926
TI - Advances in the Prevention and Treatment of High Altitude Illness.
AB - High altitude illness encompasses a spectrum of clinical entities to include:
acute mountain sickness, high altitude cerebral edema, and high altitude
pulmonary edema. These illnesses occur as a result of a hypobaric hypoxic
environment. Although a mild case of acute mountain sickness may be self-limited,
high altitude cerebral edema and high altitude pulmonary edema represent critical
emergencies that require timely intervention. This article reviews recent
advances in the prevention and treatment of high altitude illness, including new
pharmacologic strategies for prophylaxis and revised treatment guidelines.
PMID- 28411927
TI - Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia.
AB - Accidental hypothermia is an unintentional drop in core temperature to 35 degrees
C or below. Core temperature is best measured by esophageal probe. If core
temperature cannot be measured, the degree should be estimated using clinical
signs. Treatment is to protect from further heat loss, minimize afterdrop, and
prevent cardiovascular collapse during rescue and resuscitation. The patient
should be handled gently, kept horizontal, insulated, and actively rewarmed.
Active rewarming is also beneficial in mild hypothermia but passive rewarming
usually suffices. Cardiopulmonary resuscitation should be performed if there are
no contraindications to resuscitation. CPR may be delayed or intermittent.
PMID- 28411928
TI - Frostbite.
AB - Deep frostbite is a thermal injury associated with significant morbidity.
Historically, this has been associated with military personnel; however,
increasingly it is becoming an injury that afflicts the civilian population. The
use of intravenous iloprost or intra-arterial thrombolytics has led to promising
tissue salvage. This article provides an up-to-date understanding of frostbite
pathophysiology, classification, prevention, and management. It also highlights
the role of telemedicine in optimizing patient outcomes. To further the
understanding of optimal frostbite management, larger, likely multicenter, high
quality trials are required. An international frostbite register would facilitate
data gathering.
PMID- 28411929
TI - Updates in Decompression Illness.
AB - Decompression sickness and arterial gas embolism, collectively known as
decompression illness (DCI), are rare but serious afflictions that can result
from compressed gas diving exposures. Risk is primarily determined by the
pressure-time profile but is influenced by several factors. DCI can present
idiosyncratically but with a wide range of neurologic symptoms. Examination is
critical for assessment in the absence of diagnostic indicators. Many conditions
must be considered in the differential diagnosis. High-fraction oxygen breathing
provides first aid but definitive treatment of DCI is hyperbaric oxygen.
PMID- 28411930
TI - Marine Envenomation.
AB - Venomous aquatic animals are hazardous to swimmers, surfers, divers, and
fishermen. Exposures include mild stings, bites, abrasions, and lacerations.
Severe envenomations can be life threatening. This article reviews common marine
envenomations, exploring causative species, clinical presentation, and current
treatment recommendations. Recommendations are included for cnidaria, sponges,
bristle worms, crown-of-thorns starfish, sea urchins, venomous fish, stingrays,
cone snails, stonefish, blue-ringed octopus, and sea snakes. Immediate and long
term treatment options and management of common sequelae are reviewed. Antivenom
administration, treatment of anaphylaxis, and surgical indications are discussed.
PMID- 28411931
TI - North American Snake Envenomation.
AB - Native US snakes that produce clinically significant envenomation can be divided
into 2 groups, crotalids and elapids. The crotalids include rattlesnakes,
cottonmouths, and copperheads. Crotalid envenomation can result in significant
local tissue damage as well as thrombocytopenia and coagulopathy. Rarely are
bites fatal. Native US elapids are all coral snakes that possess neurotoxic venom
that can cause weakness, respiratory paralysis, and rarely death. Treatment of
both types of envenomation revolves around general supportive care and antivenom
administration when indicated. Previously advocated treatments, such as
tourniquets, venom extraction, and bite site excision are not recommended.
PMID- 28411932
TI - Arthropod Envenomation in North America.
AB - Arthropods (phylum Arthopoda) account for a higher percentage of morbidity and
mortality to humans than do mammalian bites, snake bites, or marine envenomation.
They are ubiquitous in domestic dwellings, caves, and campsites and in wilderness
settings such as deserts, forests, and lakes. Although arthropods are most
intrusive during warmer months, many are active throughout the winter,
particularly indoors. Arthropods are also nocturnal and often bite unsuspecting
victims while they are sleeping. Encounters with humans are generally defensive,
accidental, or reactive. An individual stung by an insect or bitten by an
arachnid may experience pain and local swelling, an anaphylactic reaction, or
life-threatening toxicity. This review discusses the clinical presentation and
latest treatment recommendations for bites and stings from spiders, scorpions,
bees, ants, ticks and centipedes of North America.
PMID- 28411933
TI - Wilderness Emergency Medical Services Systems.
AB - Wilderness emergency medical services (WEMS) are designed to provide high quality
health care in wilderness environments. A WEMS program should have oversight by a
qualified physician responsible for protocol development, education, and quality
improvement. The director is also ideally fully trained as a member of that
wilderness rescue program, supporting the team with real-time patient care. WEMS
providers function with scopes of practice approved by the local medical director
and regulatory authority. With a focus on providing quality patient care, it is
time for the evolution of WEMS as an integrated element of a local emergency
response system.
PMID- 28411934
TI - Tactical Combat Casualty Care and Wilderness Medicine: Advancing Trauma Care in
Austere Environments.
AB - Tactical Combat Casualty Care (TCCC) is a set of evidence-based, best-practice
prehospital trauma care guidelines customized for use on the battlefield.
Military units that have trained all of their unit members in TCCC have now
documented the lowest incidence of preventable deaths in the history of modern
warfare and TCCC is now the standard for battlefield trauma care in the US
Military. TCCC and wilderness medicine share the goal of optimizing care for
patients with trauma in austere environments that impose significant challenges
in both equipment and evacuation capability. This article reviews the current
battlefield trauma care recommendations in TCCC and discusses their applicability
to the wilderness setting.
PMID- 28411935
TI - Point-of-Care Ultrasound in Austere Environments: A Complete Review of Its
Utilization, Pitfalls, and Technique for Common Applications in Austere Settings.
AB - With the advent of portable ultrasound machines, point-of-care ultrasound (POCUS)
has proven to be adaptable to a myriad of environments, including remote and
austere settings, where other imaging modalities cannot be carried. Austere
environments continue to pose special challenges to ultrasound equipment, but
advances in equipment design and environment-specific care allow for its
successful use. This article describes the technique and illustrates pathology of
common POCUS applications in austere environments. A brief description of common
POCUS-guided procedures used in austere environments is also provided.
PMID- 28411936
TI - Is There a Doctor Onboard? Medical Emergencies at 40,000 Feet.
AB - It is estimated 2.75 billion people travel aboard commercial airlines every year
and 44,000 in-flight medical emergencies occur worldwide each year. Wilderness
medicine requires a commonsense and improvisational approach to medical issues. A
sudden call for assistance in the austere and unfamiliar surroundings of an
airliner cabin may present the responding medical professional with a "wilderness
medicine" experience. From resource management to equipment, this article sheds
light on the unique conditions, challenges, and constraints of the flight
environment.
PMID- 28411937
TI - Preparing for International Travel and Global Medical Care.
AB - Thorough pretravel preparation and medical consultation can mitigate avoidable
health and safety risks. A comprehensive pretravel medical consultation should
include an individualized risk assessment, immunization review, and discussion of
arthropod protective measures, malaria prophylaxis, traveler's diarrhea, and
injury prevention. Travel with children and jet lag reduction require additional
planning and prevention strategies; travel and evacuation insurance may prove
essential when traveling to less resourced countries. Consideration should also
be given to other high-risk travel scenarios, including the provision of health
care overseas, adventure and extreme sports, water environments and diving, high
altitude, and terrorism/unstable political situations.
PMID- 28411938
TI - Medicolegal Issues in Expedition and Wilderness Medicine.
AB - There is increased participation in wilderness expeditions to remote and austere
environments, which increases the likelihood of an accident and/or medical
emergency and the professional liability risks for trip organizers. Trip
organizers, outfitters, tour guides, and health care providers must understand
the medicolegal liabilities involved in and the legal protection and immunity
available when rendering care in austere and challenging settings to mitigate
risks and prepare for the level of medical care that may be required. There is a
great deal of variability in the legal protections provided by Good Samaritan
laws and interpretations may differ among jurisdictions.
PMID- 28411939
TI - Erratum.
PMID- 28411940
TI - Wilderness and Environmental Medicine.
PMID- 28411941
TI - Wilderness and Environmental Medicine.
PMID- 28411942
TI - Transplacental nutrient transfer in the human in vivo determined by 4 vessel
sampling.
AB - BACKGROUND: The intrauterine environment and especially the fetal nutritional
conditions affect lifelong health. There are few human in vivo studies on fetal
nutrition. The importance to test experimentally based concepts of fetal
nutrition in a human in vivo setting is becoming increasingly apparent. A way of
testing nutrient transfer in human is 4-vessel sampling, which implies blood
sampling from artery and vein on both sides of the placenta. Here we give a brief
review of the studies using the 4-vessel sampling method. METHOD: We performed
systematic searches in Ovid MEDLINE and EMBASE (Ovid) from 1946 to May 2016. The
following search terms were used to identify eligible articles: [placenta] AND
[glucose/blood glucose] OR [amino acids] OR [lipids] OR [cholesterol] OR
[nutrient] AND [blood sample] OR [biological transport] OR
[transport/transfer/exchange] OR [maternal-fetal exchange] AND [humans]. RESULTS:
The search retrieved 623 studies. After abstract scanning 25 full text articles
were evaluated and seven articles describing 4-vessel sampling were identified.
The studies had from 14 to 77 participants and reported placental transfer of
different nutrients (glucose, lactate, amino acids and arachidonic acid).
CONCLUSION: Few studies have used 4 vessel sampling to study placental nutrient
transfer in human pregnancies. Overall these studies indicate that the transfer
of nutrients between the mother and the fetus is highly "dynamic," i.e. most
nutrients may pass either way on both the maternal and fetal sides of the
placenta. Furthermore, the concept that the placenta is a metabolically highly
active organ affecting transfer of glucose, amino acids and lipids, fits the
human in vivo data. The 4-vessel method can provide essential information on the
transfer between the mother, placenta and fetus of virtually any compound.
PMID- 28411943
TI - Immunomodulatory properties of human placental mesenchymal stem/stromal cells.
AB - Mesenchymal stem/stromal cells (MSCs) are isolated from various fetal and adult
tissues such as bone marrow, adipose tissue, cord blood and placenta. Placental
MSCs (pMSCs), the main focus of this review, are relatively new MSC types that
are not as intensively studied compared with bone marrow-derived MSCs (BMMSCs).
MSCs modulate the immune functions of important immune cells involved in
alloantigen recognition and elimination, including antigen presenting cells
(APCs), T cells, B cells and natural killer (NK) cells. Clinical trials, both
completed and underway, employ MSCs to treat various human immunological
diseases, such as multiple sclerosis (MS) and type 1 diabetes. However, the
mechanisms that mediate the immunosuppressive effects of pMSCs are still largely
unknown, and the safety of pMSC use in clinical settings needs further
confirmation. Here, we review the current knowledge of the immunosuppressive
properties of placental MSCs.
PMID- 28411944
TI - Differentiation of amniotic epithelial cells into various liver cell types and
potential therapeutic applications.
AB - The aim of Regenerative Medicine is to replace or regenerate human cells, tissues
or organs in order to restore normal function. Among all organs, the liver is
endowed with remarkable regenerative capacity. Nonetheless, there are conditions
in which this ability is impaired, and the use of isolated cells, including stem
cells, is being considered as a possible therapeutic tool for the management of
chronic hepatic disease. Placenta holds great promise for the field of
regenerative medicine. It has long been used for the treatment of skin lesions
and in ophthalmology, due to its ability to modulate inflammation and promote
healing. More recently, cells isolated from the amniotic membrane are being
considered as a possible resource for tissue regeneration, including in the
context liver disease. Two cell types can be easily isolated from human amnion:
epithelial cells (hAEC) and mesenchymal stromal cells (hAMSC). However only the
first cell population has been demonstrated to be a possible source of proficient
hepatic cells. This review will summarize current knowledge on the
differentiation of hAEC into liver cells and their potential therapeutic
application.
PMID- 28411945
TI - Shallow rocky nursery habitat for fish: Spatial variability of juvenile fishes
among this poorly protected essential habitat.
AB - Coastal nursery habitats are essential for the renewal of adult fish populations.
We quantified the availability of a coastal nursery habitat (shallow
heterogeneous rocky bottoms) and the spatial variability of its juvenile fish
populations along 250km of the Catalan coastline (France and Spain). Nurseries
were present in 27% of the coastline, but only 2% of them benefited from strict
protection status. For nine taxa characteristic of this habitat, total juvenile
densities varied significantly between nursery sites along the coastline, with
the highest densities being found on the northern sites. Recruitment level (i.e.
a proxy of nursery value) was not explained by protection level, but it was
moderately and positively correlated with an anthropization index. Patterns of
spatial variations were taxa-specific. Exceptional observations of four juveniles
of the protected grouper Epinephelus marginatus were recorded. Our data on
habitat availability and recruitment levels provides important informations which
help to focus MPA management efforts.
PMID- 28411946
TI - Introduction.
PMID- 28411947
TI - Central line-associated bloodstream infections in the NICU: Successes and
controversies in the quest for zero.
AB - Central line-associated bloodstream infections (CLABSI) are among the most common
healthcare-acquired infections in the neonatal intensive care unit (NICU)
population and are associated with an increased risk of morbidity and mortality,
as well as increased healthcare costs, and duration of hospitalization. Over the
past decade, numerous local, statewide, and national quality improvement
initiatives have resulted in a significant reduction in CLABSI rates. The
majority of successful initiatives have utilized similar strategies to implement
and sustain their efforts, including education of NICU staff in the principles of
quality improvement, creation and implementation of central line insertion and
maintenance bundles and methods for assessing compliance, formation of dedicated
central line insertion and maintenance teams, and utilization of reliable and
effective methods for collecting, analyzing, and displaying data. Despite this
progress, continued work toward discovery of better practices, such as the safest
and most effective agent for cutaneous antisepsis or identification of optimal
outcome and process measures, is required if further progress is to be made.
Additionally, sustained progress in reducing the burden of neonatal infections
may require a shift in focus away from CLABSI and toward the reporting,
investigation, and prevention of all NICU-onset bacteremia.
PMID- 28411948
TI - Reporting 'Denominator' data is essential for benchmarking and quality standards
in ovarian cancer.
AB - OBJECTIVE: Combined surgery and platinum-based chemotherapy is the
internationally agreed standard therapy for advanced ovarian cancer (AOC).
However international cancer registry datasets demonstrate a significant
proportion of patients do not receive both or either therapies. Our objective was
to evaluate the effect of total patient cohort data ('Denominator') on median
overall survival (OS) and determine how frequently this was reported in
literature. METHODS: We retrospectively reviewed OS outcomes for 593 patients
diagnosed with AOC for 77 months at a regional cancer centre. Patients were
stratified into five progressively overlapping categories based on treatment
received - Primary debulking surgery (PDS), PDS or Interval debulking (IDS), all
surgery and those considered for IDS, patients receiving any treatment and total
patient cohort. A systematic search of literature was performed. RESULTS: Median
OS progressively decreased from 54.5 months in patients receiving PDS, 38.7
months in the PDS+IDS group, 35.4 months in the PDS/IDS+patients considered for
IDS, 33.3 months in patients receiving any treatment and 30.2 months in the total
patient cohort. OS in the surgically treated group was statistically
significantly different from the OS in the total patient cohort
(Denominator)(p=0.000353). Denominator descriptors were identified in 11% of
studies. CONCLUSIONS: Denominator data is critical to understanding selection and
OS in AOC. Published outcomes of selected cohorts should routinely incorporate
outcomes for all women managed within the reporting Centre. This is essential for
benchmarking and quality assurance in gynaecological cancer and should be an
integral part of any publication on outcomes from AOC.
PMID- 28411949
TI - Reliability of Echocardiographic Indicators of Pulmonary Vascular Disease in
Preterm Infants at Risk for Bronchopulmonary Dysplasia.
AB - OBJECTIVES: To determine the assessment and inter-rater reliability of
echocardiographic evaluations of pulmonary vascular disease (PVD) in preterm
infants at risk for bronchopulmonary dysplasia. STUDY DESIGN: We prospectively
studied echocardiograms from preterm infants (birthweights 500-1250 g) at 7 days
of age and 36 weeks postmenstrual age (PMA). Echocardiograms were assessed by
both a cardiologist on clinical service and a single research cardiologist.
Interpretations were reviewed for inclusion of determinants of PVD and assessed
for inter-rater reliability using the Prevalence Adjusted Bias Adjusted Kappa
Score (PABAK). RESULTS: One hundred eighty and 188 matching research and clinical
echocardiogram reports were available for the 7-day and 36-week PMA studies. At
least one of the specific qualitative measures of PVD was missing from 54% of the
clinical reports. PVD was diagnosed at 7 days in 31% and 20% of research and
clinical interpretations, respectively (PABAK score of 0.54). At 36 weeks, PH was
diagnosed in 15.6% and 17.8% of research and clinical interpretations,
respectively (PABAK score of 0.80). CONCLUSIONS: Although all qualitative
variables of PVD are not consistently provided in echocardiogram reports, the
inter-rater reliability of cardiologists evaluating measures of PVD revealed
strong agreement, especially at 36 weeks PMA. We speculate that establishment of
a protocol for echocardiographic evaluation may improve the identification of PVD
in preterm infants.
PMID- 28411950
TI - Priorities to Advance Monitoring of Ecosystem Services Using Earth Observation.
AB - Managing ecosystem services in the context of global sustainability policies
requires reliable monitoring mechanisms. While satellite Earth observation offers
great promise to support this need, significant challenges remain in quantifying
connections between ecosystem functions, ecosystem services, and human well-being
benefits. Here, we provide a framework showing how Earth observation together
with socioeconomic information and model-based analysis can support assessments
of ecosystem service supply, demand, and benefit, and illustrate this for three
services. We argue that the full potential of Earth observation is not yet
realized in ecosystem service studies. To provide guidance for priority setting
and to spur research in this area, we propose five priorities to advance the
capabilities of Earth observation-based monitoring of ecosystem services.
PMID- 28411951
TI - Reply to: "Considerations about: "Prevalence of hypertension and hypertension
phenotypes by age and gender among schoolchildren in Greece: The Healthy Growth
Study"".
PMID- 28411952
TI - Improved design of constrained model predictive tracking control for batch
processes against unknown uncertainties.
AB - In this paper, an improved constrained tracking control design is proposed for
batch processes under uncertainties. A new process model that facilitates process
state and tracking error augmentation with further additional tuning is first
proposed. Then a subsequent controller design is formulated using robust stable
constrained MPC optimization. Unlike conventional robust model predictive control
(MPC), the proposed method enables the controller design to bear more degrees of
tuning so that improved tracking control can be acquired, which is very important
since uncertainties exist inevitably in practice and cause model/plant
mismatches. An injection molding process is introduced to illustrate the
effectiveness of the proposed MPC approach in comparison with conventional robust
MPC.
PMID- 28411953
TI - Adaptive fuzzy control of a class of nonaffine nonlinear system with input
saturation based on passivity theorem.
AB - In this paper, based on the passivity theorem, an adaptive fuzzy controller is
designed for a class of unknown nonaffine nonlinear systems with arbitrary
relative degree and saturation input nonlinearity to track the desired
trajectory. The system equations are in normal form and its unforced dynamic may
be unstable. As relative degree one is a structural obstacle in system
passivation approach, in this paper, backstepping method is used to circumvent
this obstacle and passivate the system step by step. Because of the existence of
uncertainty and disturbance in the system, exact passivation and reference
tracking cannot be tackled, so the approximate passivation or passivation with
respect to a set is obtained to hold the tracking error in a neighborhood around
zero. Furthermore, in order to overcome the non-smoothness of the saturation
input nonlinearity, a parametric smooth nonlinear function with arbitrary
approximation error is used to approximate the input saturation. Finally, the
simulation results for the theoretical and practical examples are given to
validate the proposed controller.
PMID- 28411954
TI - n-3 Polyunsaturated Fatty Acids for the Management of Patients With Chronic
Kidney Disease.
PMID- 28411955
TI - Message From the Chairperson.
PMID- 28411956
TI - Medical Nutrition Therapy for Pediatric Kidney Stone Prevention, Part 3:
Cystinuria.
PMID- 28411957
TI - Elevated temperature adhesion of bioinspired polymeric micropatterns to glass.
AB - Micropatterned polymer surfaces that operate at various temperatures are required
for emerging technical applications such as handling of objects or space debris.
As the mechanical properties of polymers can vary significantly with temperature,
adhesion performance can exhibit large variability. In the present paper, we
experimentally study temperature effects on the adhesion of micropatterned
adhesives (pillar length 20um, aspect ratios 0.4 and 2) made from three different
polymers, i.e., polydimethylsiloxane (PDMS), perfluoropolyether dimethacrylate
(PFPEdma), and polyurethane (PU-ht). PU specimens showed the highest pull-off
stresses of about 57kPa at 60 degrees C, i.e., more than twice the value of
unpatterned control samples. The work of separation similarly showed a maximum at
that temperature, which was identified as the glass transition temperature, Tg.
PDMS and PFPEdma specimens were tested above their Tg. As a result, the adhesion
properties decreased monotonically (about 50% for both materials) for temperature
elevation from 20 to 120 degrees C. Overall, the results obtained in our study
indicate that the operating temperature related to the glass transition
temperature should be considered as a significant parameter for assessing the
adhesion performance of micropatterned adhesives and in the technical design of
adhesion devices.
PMID- 28411958
TI - Effects of step length and step frequency on lower-limb muscle function in human
gait.
AB - The aim of this study was to quantify the effects of step length and step
frequency on lower-limb muscle function in walking. Three-dimensional gait data
were used in conjunction with musculoskeletal modeling techniques to evaluate
muscle function over a range of walking speeds using prescribed combinations of
step length and step frequency. The body was modeled as a 10-segment, 21-degree
of-freedom skeleton actuated by 54 muscle-tendon units. Lower-limb muscle forces
were calculated using inverse dynamics and static optimization. We found that
five muscles - GMAX, GMED, VAS, GAS, and SOL - dominated vertical support and
forward progression independent of changes made to either step length or step
frequency, and that, overall, changes in step length had a greater influence on
lower-limb joint motion, net joint moments and muscle function than step
frequency. Peak forces developed by the uniarticular hip and knee extensors, as
well as the normalized fiber lengths at which these muscles developed their peak
forces, correlated more closely with changes in step length than step frequency.
Increasing step length resulted in larger contributions from the hip and knee
extensors and smaller contributions from gravitational forces (limb posture) to
vertical support. These results provide insight into why older people with weak
hip and knee extensors walk more slowly by reducing step length rather than step
frequency and also help to identify the key muscle groups that ought to be
targeted in exercise programs designed to improve gait biomechanics in older
adults.
PMID- 28411959
TI - Implementation and outcomes of an antimicrobial stewardship program:
Effectiveness of education.
AB - BACKGROUND: Unnecessary use of antibiotics is a common occurrence in hospitals.
Implementation of antibiotic stewardship programs (ASPs) has been shown to reduce
both unnecessary antibiotic use and drug-resistant bacteria. Education is a
fundamental component of an ASP. However, the effectiveness of proper uses of
antibiotics education has not been clearly analyzed. METHODS: In a 520-bed
university hospital located in northeastern Taiwan, a significantly increasing
prescription of carbapenems, specifically imipenem and meropenem, was observed.
An educational program highlighting the judicious use of carbapenems was started,
beginning in October 2013. A multidisciplinary ASP was implemented starting in
January 2014. The consumption of antibiotics, measured by defined daily dose per
1000 occupied bed-days, was compared among the pre-educational, posteducational,
and post-ASP periods. RESULTS: Compared with the pre-educational period, there
was a significant reduction in antibiotics consumption of 13% total inpatient
antibiotics (p = 0.008), 29.8% carbapenems (p = 0.001), 34.9% imipenem and
meropenem (p < 0.001), and 27% glycopeptides (p = 0.015), in the posteducational
and post-ASP periods. The major reduction emerged during the posteducational
period and was sustained after the ASP. The percentage of inpatients prescribed
with antibiotics was significantly decreased (16.2%; p < 0.001). The rate of
carbapenem-resistant Acinetobacter baumannii decreased from 70.8% to 29.6% within
7 months. CONCLUSION: A focused educational program is effective in controlling
the prescription of specific antibiotic classes in the early phase of a
multidisciplinary ASP.
PMID- 28411960
TI - Age and gender influences on the needs, concerns and strategies of CABG
caregivers.
AB - BACKGROUND: Caring for coronary artery bypass (CABG) surgery patients can be
challenging. No studies have explored caregiver burden by age and gender.
OBJECTIVE: To describe age and gender-specific concerns, needs and strategies
during the first 3 months. METHODS: Themes for burden concerns, needs and
strategies were derived from interviews of 32 CABG caregivers using constant
comparative analysis. RESULTS: Age-specific themes related to motivating exercise
(<70), applying support hose, and self-reliance (>70). Gender-specific themes
related to incision worries and transportation (all females); regulating blood
sugars, vital sign anxiety, hurrying back, reinforcing healthy behaviors, and
being there (females <70); meal planning, coordinating appointments, and anger
over self-care reminders (females >70); caregiver relief, inconsistent
information, and doing it all (all males); upsetting scars (males <70), and lost
sleep (male >70). CONCLUSIONS: Future research should validate concerns in
diverse samples so interventions can be targeted to support male and female
caregivers by age groups.
PMID- 28411961
TI - Nutrition in the first 1000 days and respiratory health: A descriptive review of
the last five years' literature.
AB - The aim of this paper is to discuss the current evidence regarding short and long
term health respiratory effects of nutrients and dietary patterns during the
first 1000 days from conception. Population of interest included children from
birth to two years and their mothers (during pregnancy and lactation). Studies
were searched on MEDLINE(r) and Cochrane database, inserting individually and
using the Boolean ANDs and ORs, 'nutrients', 'micronutrients', 'LC-PUFA',
'Mediterranean Diet', 'human milk', 'complementary food', 'pregnancy',
'respiratory disease', 'pulmonary disease', 'asthma', 'epigenetics', 'first 1000
days', 'maternal diet' and 'respiratory health'. All sources were retrieved
between 01-09-2015 and 07-12-2016. While unhealthy maternal dietary patterns
(high fat intake) during pregnancy can result in alteration of foetal lung
development, with increased risk of respiratory disorders, Mediterranean diet has
been associated with a lower risk of allergic sensitisation and allergic
rhinitis. Breastfeeding has beneficial effects on respiratory infections while
evidences about its protective effect on allergic disorders are unclear. During
complementary feeding there is no evidence to avoid or encourage exposition to
'highly allergenic' foods to have modification of tolerance development. In
children from birth to two years of age, Mediterranean diet has been associated
with a lower risk of atopy, wheezing and asthma. Micronutrients, antioxidant and
LCPUFA supplementation is not recommended and a whole food approach should be
preferred, except for Vitamin D.
PMID- 28411962
TI - Epidemiology and pathophysiology of malignancy in common variable
immunodeficiency?
AB - Common variable immunodeficiency (CVID) is a diagnostic category of primary
immunodeficiency (PID) which may present with heterogeneous disorders including
recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other
types of malignancies. Generally, the incidence of malignancy in CVID patients is
around 1.5-20.7% and usually occurs during the 4th-6th decade of life. Non
Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours
of stomach, breast, bladder and cervix. The exact pathological mechanisms for
cancer development in CVID are not fully determined; however, several mechanisms
including impaired genetic stability, genetic predisposition, immune
dysregulation, impaired clearance of oncogenic viruses and bacterial infections,
and iatrogenic causes have been proposed to contribute to the high susceptibility
of these patients to malignancies.
PMID- 28411963
TI - Using a knowledge-based planning solution to select patients for proton therapy.
AB - BACKGROUND AND PURPOSE: Patient selection for proton therapy by comparing
proton/photon treatment plans is time-consuming and prone to bias. RapidPlanTM, a
knowledge-based-planning solution, uses plan-libraries to model and predict organ
at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan,
utilizing an algorithm based only on photon beam characteristics, could generate
proton DVH-predictions and whether these could correctly identify patients for
proton therapy. MATERIAL AND METHODS: ModelPROT and ModelPHOT comprised 30 head
and-neck cancer proton and photon plans, respectively. Proton and photon
knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH
prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR
doses. KBPs and manual plans were compared using salivary gland and swallowing
muscle mean doses. For illustration, patients were selected for protons if
predicted ModelPHOT mean dose minus predicted ModelPROT mean dose
(DeltaPrediction) for combined OARs was >=6Gy, and benchmarked using achieved KBP
doses. RESULTS: Achieved and predicted ModelPROT/ModelPHOT mean dose R2 was
0.95/0.98. Generally, achieved mean dose for ModelPHOT/ModelPROT KBPs was
respectively lower/higher than predicted. Comparing ModelPROT/ModelPHOT KBPs with
manual plans, salivary and swallowing mean doses increased/decreased by <2Gy, on
average. DeltaPrediction>=6Gy correctly selected 4 of 5 patients for protons.
CONCLUSIONS: Knowledge-based DVH-predictions can provide efficient, patient
specific selection for protons. A proton-specific RapidPlan-solution could
improve results.
PMID- 28411964
TI - Understanding what matters: An exploratory study to investigate the views of the
general public for priority setting criteria in health care.
AB - Health care policy makers internationally are increasingly expressing commitment
to consultation with, and incorporation of, the views of the general public into
the formulation of health policy and the process of setting health care
priorities. In practice, however, there are relatively few opportunities for the
general public to be involved in health care decision-making. In making resource
allocation decisions, funders, tasked with managing scarce health care resources,
are often faced with difficult decisions in balancing efficiency with equity
considerations. A mixed methods (qualitative and quantitative) approach
incorporating focus group discussions and a ranking exercise was utilised to
develop a comprehensive list of potential criteria for setting priorities in
health care formulated from the perspective of members of the general public in
Australia. A strong level of congruence was found in terms of the rankings of the
key criteria with the size of the health gain, clinical effectiveness, and the
ability to provide quality of life improvements identified consistently as the
three most important criteria for prioritising the funding of an intervention.
Findings from this study will be incorporated into a novel DCE framework to
explore how decision makers and members of the general public prioritize and
trade off different types of health gain and to quantify the weights attached to
specific efficiency and equity criteria in the priority setting process.
PMID- 28411965
TI - Dynamic Cerebral Autoregulation Assessment Using Extracranial Internal Carotid
Artery Doppler Ultrasonography.
AB - Transcranial Doppler ultrasonography of the middle cerebral artery (MCA) is
frequently used to assess dynamic cerebral autoregulation (dCA); however, this is
difficult in patients with poor temporal bone windows. In the study described
here, we investigated the agreement and sensitivity of dCA indices determined
from the extracranial internal carotid artery (ICA) and those determined from the
MCA. Measurements for 32 stroke patients and 59 controls were analyzed.
Measurement of the mean flow correlation index (Mx) and transfer function
analysis based on spontaneous blood pressure fluctuation were simultaneously
performed for the extracranial ICA and MCA. The mean values of Mx and phase shift
did not significantly differ between the ICA and MCA (mean difference: Mx = 0.01;
phase shift of very low frequency [VLF] = 0.7 degrees , low frequency [LF] = 3.3
degrees and high frequency = 4.5 degrees ), but the gains in VLF and LF in the
ICA were significantly lower than those in the MCA (mean difference: gain of VLF
= -0.13, gain of LF = -0.10). The intra-class correlation coefficient between the
dCA indices of the ICA and MCA was favorable in Mx (0.76) and the phase shift of
VLF (0.72). The area under the receiver operating characteristic curve for stroke
diagnosis did not differ among the dCA indices. We conclude that dCA assessed
from the ICA is as effective as that from the MCA, but the results are not
interchangeable.
PMID- 28411966
TI - Ultrasound Screening for Adverse Local Tissue Reaction after Hip Arthroplasty.
AB - Early detection of adverse local tissue reaction (ALTR) to prosthetic hip wear
debris is vital to improve the success of revision surgery. Magnetic resonance
imaging with metal artefact reduction sequencing (MARS MRI) is considered the
modality of choice to provide cross-sectional imaging of the soft tissues. The
areas adjacent to the prosthesis are, however, not readily imaged using these
protocols. Ultrasound has also been recommended as an imaging modality in the
follow-up of hip replacement surgery. We decided to characterise the typical
ultrasound findings in a group of patients undergoing routine biennial review of
arthroplastic hips with particular reference to the hip capsule, femoral neck and
iliopsoas bursa and tendon adjacent to the implant. Fifty-two patients with a
mean (+/-SD) age of 60.4 (+/-12) y were prospectively recruited. Twelve patients
had bilateral hip prostheses, giving 64 hips for analysis. Mean (+/-SD) age of
the prosthesis in situ was 8.2 (+/-3.3) y. Data were grouped on the basis of the
shape of the iliofemoral ligament. The median (range) maximal anteroposterior
synovial thickness was 5 (2-8) mm in the normal concave iliofemoral ligament
group and 7 (4-56) mm in the abnormal straight/convex iliofemoral ligament group
(p = 0.001). The anteroposterior iliopsoas tendon measurement was 5 (3-8) mm in
the normal group and 5 (4-8) mm in the abnormal group (p = 0.065). ALTR
development in asymptomatic well-functioning prostheses may be recognised earlier
using ultrasound rather than MARS MRI by carefully assessing the shape of the
iliofemoral ligament. Ultrasound findings of an abnormal straight or convex
ligament may be suggestive of early ALTR and warrant streaming of patients to a
more frequent surveillance program.
PMID- 28411968
TI - Waterlining, Shebanging, and Monkey Water: An Unrecognized Route of Heroin Abuse.
PMID- 28411967
TI - Utility of relative ADC ratio in patient selection for endovascular
revascularization of large vessel occlusion.
AB - PURPOSE: The relative apparent diffusion coefficient (ADC) ratio on magnetic
resonance imaging (MRI) can be used to evaluate the degree of ischemia. Here, we
assessed the predictability of ischemic reversibility and the risk of hemorrhagic
transformation using the relative ADC ratio. METHODS: This single-center
retrospective study analyzed 56 patients with acute occlusion of the internal
carotid artery (ICA) or the middle cerebral artery (M1) with endovascular
revascularization. Diffusion-weighted imaging (DWI) lesions were classified as
reversible lesions, final infarct lesions, and hemorrhagic or non-hemorrhagic
regions. The relative ADC ratio was calculated in each DWI lesion and was defined
as the ratio of ADC pixel values within affected territory to ADC pixel values in
contralateral normal brain regions. RESULTS: The average relative ADC ratio was
0.890+/-0.045 in reversible DWI lesion and 0.640+/-0.041 in final infarct DWI
lesion (P<0.001). In 4 cases with hemorrhagic transformation, hemorrhagic
transformation regions were 0.557+/-0.049 and non-hemorrhagic transformation
regions were 0.762+/-0.042 (P<0.001). In addition, percentage DWI improvement was
inversely correlated with DWI lesion volume at the time of hospitalization (r=
0.840) and onset-to-reperfusion time (r=-0.765), but no correlation was noted
with patient age (r=-0.043) or the first NIHSS score (r=-0.277). CONCLUSIONS: The
relative ADC ratio may be useful for predicting DWI reversibility and post
reperfusion hemorrhagic transformation, even in patients with an unknown time of
onset.
PMID- 28411969
TI - Valproate-Induced Hyperammonemic Encephalopathy in General Hospital Patients With
One or More Psychiatric Disorders.
AB - BACKGROUND: Divalproex sodium/valproic acid (VPA) is an antiepileptic drug
approved for use in epilepsy and bipolar disorder. Valproate-induced
hyperammonemia occurs in up to 50% of VPA-treated patients, some of whom may
become encephalopathic. Valproate-induced hyperammonemic encephalopathy (VHE) is
thought to be rare, and for a variety of reasons, the diagnosis requires a high
index of suspicion. OBJECTIVE: The study's goals are to determine how common VHE
is, and the quality of treatment provided when diagnosed. METHODS: Retrospective,
cross-sectional survey of general hospital patients. The hospital's laboratory
and pharmacy databases were combined to identify a cohort of all VPA-treated
patients who developed hyperammonemia during a 5-year period. Hospital records of
the subset of patients with a psychiatric disorder were selected and reviewed for
data collection. RESULTS: Twenty of 793 (2.52%) VPA-treated patients had signs
and symptoms consistent with VHE. The majority were White males on multiple
psychotropic agents. Valproate was appropriately discontinued in 8 (40%)
patients. Lactulose was the only ammonia-lowering drug used, and it was
administered to 6 patients and only one among them had VPA discontinued.
CONCLUSION: Study results indicate that VHE may be more common in psychiatric
patients than previously assumed but underrecognized and inadequately treated.
The diagnosis of VHE requires a high index of suspicion. Outcome is favorable
once it is recognized and treated appropriately.
PMID- 28411970
TI - Long-term outcomes of the New Jersey nurse faculty preparation program scholars.
AB - BACKGROUND: Rising concerns over the capacity of nursing education to prepare
enough nurses to meet population demand have received national attention. The
Robert Wood Johnson Foundation implemented the New Jersey Nursing Initiative
Faculty Preparation Program to address nursing workforce issues in New Jersey.
PURPOSE: This paper describes program and scholar outcomes and provides
recommendations for nurse faculty development. METHODS: This descriptive study
uses data from scholar surveys and interviews with grantees. DISCUSSION: Findings
suggest that a faculty preparation program that targets doctoral students and
includes financial support, socialization to the faculty role, and formal
education courses produces graduates who maintain a career in nursing education
for up to three years after program completion. However, most master's-level
students who also received formal preparation in nursing education were employed
in clinical practice. CONCLUSIONS: Program developers must carefully consider the
design of programs that integrate faculty preparation and advanced clinical
training for master's-level students.
PMID- 28411971
TI - MDRD or CKD-EPI for glomerular filtration rate estimation in living kidney
donors.
AB - INTRODUCTION: The evaluation of the measured Glomerular Filtration Rate (mGFR) or
estimated Glomerular Filtration Rate (eGFR) is key in the proper assessment of
the renal function of potential kidney donors. We aim to study the correlation
between glomerular filtration rate estimation equations and the measured methods
for determining renal function. MATERIAL AND METHODS: We analysed the
relationship between baseline GFR values measured by Tc-99m-DTPA (diethylene
triamine-pentaacetate) and those estimated by the four-variable Modification of
Diet in Renal Disease (MDRD4) and Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equations in a series of living donors at our
institution. RESULTS: We included 64 donors (70.6% females; mean age 48.3+/-11
years). Baseline creatinine was 0.8+/-0.1 mg/dl and it was 1.1+/-0.2 mg/dl one
year after donation. The equations underestimated GFR when measured by Tc99m-DTPA
(MDRD4-9.4 +/- 25ml/min, P<.05, and CKD-EPI-4.4 +/- 21ml/min). The correlation
between estimation equations and the measured method was superior for CKD-EPI
(r=.41; P<.004) than for MDRD4 (r=.27; P<.05). eGFR decreased to 59.6+/-11
(MDRD4) and 66.2+/-14ml/min (CKD-EPI) one year after donation. This means a mean
eGFR reduction of 28.2+/-16.7 ml/min (MDRD4) and 27.31+/-14.4 ml/min (CKD-EPI) at
one year. CONCLUSIONS: In our experience, CKD-EPI is the equation that better
correlates with mGFR-Tc99m-DTPA when assessing renal function for donor screening
purposes.
PMID- 28411972
TI - Influence of cognitive style on information processing and selection of yogurt
labels: Insights from an eye-tracking study.
AB - Cognitive styles are characteristic and stable ways in which people acquire,
organize and use information for solving problems and making decisions. Field
dependence/independence is one of the most studied cognitive styles. Field
independent subjects are characterized by having less difficulty in separating
information from its contextual surroundings and being less likely to be
influenced by external cues than field dependent individuals. The present work
aimed at studying the influence of field dependence/independence cognitive style
on consumers' visual processing and choice of yogurt labels. One hundred and
thirty three consumers completed a choice conjoint task. They were asked to
select their preferred yogurt label from each of 16 pairs of labels. While they
completed the task their eye movements were recorded using an eye-tracker. Then,
consumers were asked to complete the Group Embedded Figure Test to determine
their cognitive style. Consumers were divided into two groups with different
cognitive styles: 58% of the sample was characterized as field dependent and 42%
as field independent. When making their choices, field dependent consumers tended
to engage in less thoughtful information processing than field independent
consumers and they made fewer fixations on traditional nutritional information.
Besides, cognitive style significantly affected the relative importance of fat
and sugar content on consumer choices and modulated the influence of the traffic
light system. Field dependent consumers gave less importance to the nutritional
composition of the yogurts than field independent consumers for selecting their
preferred label. Results from this work suggest that studying the psychological
underpinnings of consumers' decision making process when selecting food products
has a great potential to contribute to a better understanding of how eating
patterns and consumer preferences are shaped.
PMID- 28411973
TI - Antioxidants: Characterization, natural sources, extraction and analysis.
AB - Recently many review papers regarding antioxidants from different sources and
different extraction and quantification procedures have been published. However
none of them has all the information regarding antioxidants (chemistry, sources,
extraction and quantification). This article tries to take a different
perspective on antioxidants for the new researcher involved in this field.
Antioxidants from fruit, vegetables and beverages play an important role in human
health, for example preventing cancer and cardiovascular diseases, and lowering
the incidence of different diseases. In this paper the main classes of
antioxidants are presented: vitamins, carotenoids and polyphenols. Recently, many
analytical methodologies involving diverse instrumental techniques have been
developed for the extraction, separation, identification and quantification of
these compounds. Antioxidants have been quantified by different researchers using
one or more of these methods: in vivo, in vitro, electrochemical,
chemiluminescent, electron spin resonance, chromatography, capillary
electrophoresis, nuclear magnetic resonance, near infrared spectroscopy and mass
spectrometry methods.
PMID- 28411974
TI - Improvement of radio frequency (RF) heating uniformity on low moisture foods with
Polyetherimide (PEI) blocks.
AB - Radio frequency (RF) heating is rapid, volumetric, and can penetrate most food
packaging material. Thus, it is suited for in-packaged food pasteurization
applications. However, the non-uniform heating problem needs to be resolved. In
this study, a method of adding Polyetherimide (PEI) cylindrical blocks on top of
and at the bottom of peanut butter samples in a cylindrical jar (d=10cm, h=5cm)
was evaluated to improve RF heating uniformity. A computer simulation model built
with COMSOL Multiphysics(r) was used for heating pattern prediction, and a new
temperature uniformity index was proposed to suitably evaluate pasteurization
process heating uniformity. Results showed that a pair of PEI blocks with a
diameter of 8cm among all five diameters (2, 4, 6, 8, and 10cm) added to the cold
spots of a given peanut butter sample could make the sample reach the best
heating uniformity. Furthermore, the best height of PEI blocks with a diameter of
8cm that allows the sample to be heated most uniformly was found to be 1.3cm
after sweeping from 0.1 to 2.3cm with a step of 0.1cm. Simulation results also
showed that the combination of PEI surrounding and the addition of 8cm diameter
PEI blocks could further control the temperature distribution range in peanut
butter within 7.1 degrees C when the peanut butter was heated from 23 to 70
degrees C. The newly developed temperature uniformity index provided a more
reasonable evaluation on heating uniformity of pasteurization process than the
traditional uniformity index.
PMID- 28411975
TI - Application of microsatellite markers as potential tools for traceability of
Girgentana goat breed dairy products.
AB - In livestock, breed assignment may play a key role in the certification of
products linked to specific breeds. Traceability of farm animals and
authentication of their products can contribute to improve breed profitability
and sustainability of animal productions with significant impact on the rural
economy of particular geographic areas and on breed and biodiversity
conservation. With the goal of developing a breed genetic traceability system for
Girgentana dairy products, the aim of this study was to identify specific
microsatellite markers able to discriminate among the most important Sicilian
dairy goat breeds, in order to detect possible adulteration in Girgentana dairy
products. A total of 20 microsatellite markers were analyzed on 338 individual
samples from Girgentana, Maltese, and Derivata di Siria goat breeds. Specific
microsatellite markers useful for traceability of dairy products were identified.
Eight microsatellite markers showed alleles present at the same time in Maltese
and Derivata di Siria and absent in Girgentana and, therefore, they were tested
on DNA pools of the three breeds. Considering the electropherograms' results,
only FCB20, SRCRSP5, and TGLA122 markers were tested on DNA samples extracted
from cheeses of Girgentana goat breed. These three microsatellite markers could
be applied in a breed genetic traceability system of Girgentana dairy products in
order to detect adulteration due to Maltese and Derivata di Siria goat breeds.
PMID- 28411976
TI - How do Brazilian consumers perceive a non-traditional and innovative fruit juice?
An approach looking at the packaging.
AB - Consumer interest in nutritious and innovative foods encourages the development
of products based on raw materials with nutraceutical potential. The health
benefits provided by pomegranate have been recognized; therefore, the development
of pomegranate juice may match consumer expectations regarding this goal.
However, the concept has to first be accepted by the consumer. The aim of the
study was to utilize a rating based conjoint analysis to investigate how
Brazilian consumers perceive pomegranate juice by identifying the role of
packaging attributes relevant to the consumer's intention to purchase. Five
factors were considered in the study: technology used in the juice production
(high hydrostatic pressure - HHP - a technology that preserves nutritional and
sensory properties), antioxidants, price, preservatives, and colorant. Eight
hypothetical pomegranate juice packages were created following an incomplete
block design and evaluated by 150 fruit juice consumers. Three clusters were
identified. The average results revealed that antioxidants were the attribute of
greatest relative importance to cluster 1 (RI: 36%), followed by HHP (RI: 25%)
and colorants (14%). Consumers in cluster 2 considered price as the most
important attribute (RI: 41%), followed by antioxidants (RI: 21%) and HHP (RI:
18%). Cluster 3, as well as cluster 2, considered price the most important
attribute (RI: 28%), followed by antioxidants (RI: 26%) and HHP (RI: 22%). The
results showed that consumers valued information on the health benefits of
antioxidants as well as on the technology, suggesting that both types of
information may be relevant tools to increase the intention to purchase the
product. The application of HHP for pomegranate juice processing was positively
perceived by consumers, suggesting a potential commercial application in the
Brazilian industry.
PMID- 28411977
TI - Influence of anionic dietary fibers (xanthan gum and pectin) on oxidative
stability and lipid digestibility of wheat protein-stabilized fish oil-in-water
emulsion.
AB - The influence of two anionic dietary fibers (xanthan gum and pectin) on the
oxidative stability and lipid digestibility of fish oil emulsions stabilized by
wheat protein (gliadin) was investigated. Lipid oxidation was determined by
measuring lipid hydroperoxides and TBARS of the emulsions during storage, while
protein oxidation was measured using fluorescence spectroscopy. Lipid and protein
oxidation was faster at pH3.5 than at pH7, which may have been due to increased
iron solubility under acidic conditions. Xanthan gum inhibited lipid and protein
oxidation, which was attributed to its ability to bind iron ions. Conversely,
pectin promoted oxidation, which was attributed to the presence of endogenous
transition metals in the polysaccharide ingredient. In vitro digestion was
carried out to evaluate the digestibility of oil droplets in emulsions with or
without polysaccharides. Both xanthan gum and pectin significantly increased the
rate of lipid digestion, which was attributed to their ability to inhibit droplet
aggregation under gastrointestinal conditions. These results have important
implications for designing emulsion-based functional foods with improved
oxidative stability and lipid digestibility.
PMID- 28411978
TI - Safety evaluation of tangeretin and the effect of using emulsion-based delivery
system: Oral acute and 28-day sub-acute toxicity study using mice.
AB - Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging
group of bioactive compounds with wide arrays of disease prevention
functionalities. To understand the potential oral toxicity, tangeretin, being one
of the most abundant polymethoxyflavones from natural sources, was used as model
compound for the safety evaluation. Acute oral toxicity study was conducted using
both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of
tangeretin in oil suspension from single gavage administration. No evidence of
death was observed during 14-day post-administration period. Alterations of the
hepatic cell and clinical chemistry profile increased dose dependently and
exhibited distinct injury recovery pattern among different sexes. To determine
the potential safety concern related to emulsification, the sub-acute toxicity of
tangeretin in emulsion was evaluated and compared with un-processed oil
suspension when conducting the sub-acute toxicity study over 28days. In the sub
acute study, emulsion system did not induce a significant increase of toxicity
response. However, the daily low-dose application of tangeretin showed U-shaped
dose-response pattern in regard to hepatic alteration. The result from this study
can serve as a good safety reference for future application of polymethoxyflavone
as a functional ingredient in food.
PMID- 28411979
TI - Peroxidase (POD) and polyphenol oxidase (PPO) photo-inactivation in a coconut
water model solution using ultraviolet (UV).
AB - The interest in coconut water as a beverage is increasing due, not only to its
sensory properties, but also to its nutritional characteristics. Even so, several
challenges limit its processing, the inactivation of the polyphenol oxidase (PPO)
and peroxidase (POD) enzymes being the most important. Although the inactivation
of these enzymes has been extensively studied in coconut water, both by
conventional and emerging technologies, the technologies evaluated so far are
either not effective in the inactivation of these enzymes and/or result in
undesirable changes. This work evaluated the photo-inactivation of POD and PPO in
a coconut water model solution using ultraviolet radiation (UV). Both enzymes
showed continuous inactivation behaviour in relation to the processing time, this
being described by a two-portion inactivation kinetics. A possible mechanism for
the observed photo-inactivation was proposed, involving steps of molecular
unfolding and aggregation. The POD activity after 15min of processing was ~5% of
its original value, and reduced to ~1% after 30min of UV processing. After 15min
of processing, PPO activity was ~8% of its original value, falling to ~2% after
30min of UV processing. The results obtained highlight the potential use of the
ultraviolet radiation to inactivate both enzymes in coconut water.
PMID- 28411980
TI - Stability of flocculated particles in concentrated and high hydrophilic solid
layer-by-layer (LBL) emulsions formed using whey proteins and gum Arabic.
AB - The objective of the present study was to investigate flocculation in layer-by
layer (LBL) emulsion systems with high total solids content and deflocculation at
various pH conditions, and the effects of whey protein isolate (WPI)
concentration and total solids content on the stability of LBL emulsions. WPI
(1.96% (1WPI) or 10.71% (10WPI), w/w in water) was prepared in water and high
pressure homogenized with sunflower oil (10%, w/w, of total emulsion). Gum Arabic
(0.15%, w/w, in total emulsion) was added to assemble electrostatically on WPI at
oil particle interfaces at pH3.5 using aqueous citric acid (10% w/w) forming LBL
emulsion. The zeta-potential measurements showed charge reversal upon addition of
gum Arabic solution into single layer (SL) emulsion confirming the formation of
LBL interface. Trehalose:maltodextrin mixture (1:1, w/w, total emulsion, 28.57%
(28) or 57.14% (57), w/w, in water) was used in the continuous phase. The high
total solids content of the system results in depletion flocculation of the
particles leading to bridging flocculation without coalescence as deflocculation
into individual particles occurred with increasing pH from pH3.5 to pH6.5 in
10WPI systems. Deflocculation was evident in 10WPI-28 and 10WPI-57 as found from
a decreased zeta-average diameter and visually under microscope. Coalescence was
observed in 1WPI systems. Viscosity of the systems was significantly (P<0.05)
increased with higher total solids content. Accelerated destabilization test
showed that systems at higher WPI and total solids contents exhibited the highest
stability against creaming. Deflocculation in LBL systems can be controlled by pH
while high solids in the aqueous phase provide stability against creaming.
PMID- 28411981
TI - Sweetness potency and sweetness synergism of sweeteners in milk and coffee
systems.
AB - This study investigated the presence of sweetness synergism in milk and instant
coffee systems. It consists of three parts: 1) modeling concentration-sweetness
intensity curves of sweeteners (stevia, sucralose, xylose, tagatose and
erythritol); 2) measuring the sweetness potencies of sweeteners compared to
sucrose at wide concentration range; and 3) investigating the presence of
sweetness synergisms in binary sweetener mixtures. The panelists evaluated
sweetness and other sensory characteristics of sweeteners using descriptive
analysis. Based on the modeled curve derived from step 1, the concentration of
each sweetener with sweetness intensity equal to 2.5% or 2.8% sucrose was
calculated for milk and coffee systems, respectively. For the sweetness synergism
study, one type of intense sweetener was mixed with one type of bulk sweetener,
each eliciting 2.5% or 2.8% equi-sweetness to sucrose, and compared with 5%
sucrose added to a milk system or 5.6% sucrose added to a coffee system. The
sweetness potencies of bulk sweeteners generally increased whereas the sweetness
potencies of intense sweeteners decreased as the concentration increased. The
binary sweetener mixtures mostly showed additivity in milk and suppression in
coffee system rather than synergism when the concentration dependent nature of
sweetness potency for each sweetener was taken into account.
PMID- 28411982
TI - Interactions of caseins with phenolic acids found in chocolate.
AB - To investigate the interactions between caseins and phenolic acids, such as the
ones present in chocolate, casein was incubated with protocatechuic acid or p
coumaric acid at 55 degrees C. In addition, casein was isolated from chocolate
and the phenolic compounds within these caseins were quantified. Electrophoresis
results revealed that casein-phenolic interactions were induced by incubation;
minor aggregation of casein subunits was observed after incubation of casein with
protocatechuic acid. Minor aggregation of casein isolated from milk chocolate was
also observed. In vitro hydrolysis of casein control, casein-protocatechuic acid,
casein-p-coumaric acid, caseins isolated from milk chocolate and white chocolate
using trypsin showed degree of hydrolysis of 19.3, 18.6, 17.7, 10.4 and 17.8%
respectively. The presence of protocatechuic acid and p-coumaric acid in the
model system and the presence of phenolic compounds in milk chocolate, in
addition to the structural changes occurring during processing, affected the
peptide profiles of casein hydrolysates.
PMID- 28411983
TI - Biologically active peptides: Processes for their generation, purification and
identification and applications as natural additives in the food and
pharmaceutical industries.
AB - Recent technological advances have created great interest in the use of
biologically active peptides. Bioactive peptides can be defined as specific
portions of proteins with 2 to 20 amino acids that have desirable biological
activities, including antioxidant, anti-hypertensive, antithrombotic, anti
adipogenic, antimicrobial and anti-inflammatory effects. Specific
characteristics, including low toxicity and high specificity, make these
molecules of particular interest to the food and pharmaceutical industries. This
review focuses on the production of bioactive peptides, with special emphasis on
fermentation and enzymatic hydrolysis. The combination of different technologies
and the use of auxiliary processes are also addressed. A survey of isolation,
purification and peptide characterization methods was conducted to identify the
major techniques used to determine the structures of bioactive peptides. Finally,
the antioxidant, antimicrobial, anti-hypertensive, anti-adipogenic activities and
probiotic-bacterial growth-promoting aspects of various peptides are discussed.
PMID- 28411984
TI - Capability of exopolysaccharide-producing Lactobacillus paraplantarum BGCG11 and
its non-producing isogenic strain NB1, to counteract the effect of
enteropathogens upon the epithelial cell line HT29-MTX.
AB - The putative protective role of the exopolysaccharide (EPS)-producing
Lactobacillus paraplantarum BGCG11, and its non-EPS-producing isogenic strain
NB1, was tested upon HT29-MTX monolayers challenged with seven opportunistic
pathogens. The probiotic strain Lactobacillus rhamnosus LMG18243 (GG) was used as
a reference bacterium. Tested lactobacilli were able to efficiently reduce the
attachment to HT29-MTX of most pathogens. Lb. paraplantarum NB1 and Lb. rhamnosus
GG were more efficient reducing the adhesion of Clostridium difficile or Yersinia
enterocolitica than Lb. paraplantarum BGCG11, while strain BGCG11 reduced, to a
greater extent, the adhesion of Escherichia coli and Listeria monocytogenes. The
detachment and cell lysis of HT29-MTX monolayers in the presence of pathogens
alone and co-incubated with lactobacilli or purified EPS was followed. L.
monocytogenes induced the strongest cell detachment among the seven tested
pathogens and this effect was prevented by addition of purified EPS-CG11. The
results suggest that this EPS could be an effective macromolecule in protection
of HT29-MTX cells from the pathogen-induced lysis. Regarding innate intestinal
barrier, the presence of C. difficile induced the highest IL-8 production in HT29
MTX cells and this capability was reinforced by the co-incubation with Lb.
paraplantarum NB1 and Lb. rhamnosus GG. However, the increase in IL-8 production
was not noticed when C. difficile was co-incubated with EPS-producing Lb.
paraplantarum BGCG11 strain or its purified EPS-CG11 polymer, thus indicating
that the polymer could hinder the contact of bacteria with the intestinal
epithelium. The measurement of mucus secreted by HT29-MTX and the expression of
muc1, muc2, muc3B and muc5AC genes in the presence of pathogens and lactobacilli
suggested that all lactobacilli strains are weak "co-adjuvants" helping some
pathogens to slightly increase the secretion of mucus by HT29-MTX, while purified
EPS-CG11 did not induce mucus secretion. Taking altogether, Lb. paraplantarum
BGCG11 could act towards the reinforcement of the innate mucosal barrier through
the synthesis of a physical-protective EPS layer which could make difficult the
contact of the pathogens with the epithelial cells.
PMID- 28411986
TI - Changes in dietary fiber fractions and gut microbial fermentation properties of
wheat bran after extrusion and bread making.
AB - The dietary fiber in wheat bran, principally non-starch polysaccharides (NSP), is
mostly water-unextractable and is poorly utilized by human gut microbiota. The
purpose of this study was to determine the change in water-extractability of NSP
in wheat bran upon extrusion and then to determine if extrusion impacts the
availability of NSP for fermentation by the fecal microbiota during in vitro
fecal fermentation. A secondary objective was to incorporate extruded bran into a
product formulation to determine if changes in WE-NSP and NSP fermentation were
maintained in a finished product. Bran was extruded using combinations of high or
low moisture (15% and 30% wb) and high or low screw speed (120 and 250rpm). All
extrusion conditions resulted in increases in WE-NSP and fecal microbiota short
chain fatty acid (SCFA) production upon fermentation compared with unextruded
bran. Low screw speed and low moisture resulted in the greatest increase in WE
NSP (3-fold) as well as the highest production of SCFA during fermentation (1.4
fold) compared with unextruded bran. Whole wheat breads containing extruded bran
did not show increases in either WE-NSP or SCFA production compared with the
control. In conclusion, extrusion of wheat bran increased WE-NSP, which enabled
greater fermentability by human fecal microbiota. However, once extruded bran was
used in a whole wheat bread formulation the changes in fermentation outcomes were
no longer evident.
PMID- 28411985
TI - Stability of probiotic Lactobacillus plantarum in dry microcapsules under
accelerated storage conditions.
AB - This study investigated the stability of freeze dried and fluid bed dried
alginate microcapsules coated with chitosan containing model probiotic bacteria,
Lactobacillus plantarum, during storage for up to 45days at different water
activities (0.11, 0.23, 0.40 and 0.70) and temperatures (4, 30 and 37 degrees C).
The loss in cell viability was around 0.8 log in the case of fluid bed drying and
around 1.3 in the case of freeze drying, with the former method resulting in
dried capsules of smaller size (~1mm vs 1.3mm), more irregular shape, and with a
rougher surface. In both cases, the water activity and water content were less
than 0.25 and 10% w/w, respectively, which favours high storage stability. The
storage stability studies demonstrated that as the water activity and temperature
decreased the survival of the dried encapsulated cells increased. Considerably
better survival was observed for fluid bed dried encapsulated cells compared to
freeze dried encapsulated cells and freeze dried free cells with 10% sucrose
(control), and in some cases, e.g. at 4 and 30 degrees C at water activities of
0.11, 0.23 and 0.40, there was more than 1 log difference after 45days, with
concentrations higher than 108CFU/g after 45days of storage. The results indicate
that fluid bed drying is an effective and efficient manufacturing method to
produce probiotic containing capsules with enhanced storage stability.
PMID- 28411987
TI - Structural and viscoelastic characterization of ternary mixtures of sunflower
oil, saturated monoglycerides and aqueous phases containing different bases.
AB - The structure at different length scales and the viscoelastic properties of
ternary mixtures composed of saturated monoglycerides, sunflower oil and aqueous
solutions of weak bases (KHCO3, NaHCO3, and NH4HCO3) or strong bases (NaOH and
KOH) were investigated. The characteristics of ternary mixtures were studied
systematically by using polarized light microscopy, differential scanning
calorimetry (DSC), synchrotron X-ray diffraction (XRD) and rheological analysis.
Results showed that the base type and concentration greatly affected the
structure of the mixtures. The use of strong bases allowed gelled systems to be
obtained only at low concentrations (<10mM). On the contrary, the presence of
weak bases induced gelling at all concentrations considered (from 1 to 1000mM).
The increase of base concentration led to a reduction of the mean droplet
diameter and melting temperature. At the same time, the viscoelastic
characteristics as a function of base concentration followed a more complex
behavior: G' and G" progressively decreased as the salt concentration increased
in a concentration range from 1 to 100mM, while the rheological parameters
increased when salt concentration increased from 100 to 1000mM. The structural
and viscoelastic behavior of systems prepared with different salts were commonly
independent of the cation present in the medium. Results highlight that it is
possible to tailor the structure of these gels by using specific bases.
PMID- 28411988
TI - Effect of drying, storage temperature and air exposure on astaxanthin stability
from Haematococcus pluvialis.
AB - Astaxanthin is a powerful antioxidant with various health benefits such as
prevention of age-related macular degeneration and improvement of the immune
system, liver and heart function. To improve the post-harvesting stability of
astaxanthin used in food, feed and nutraceutical industries, the biomass of the
high astaxanthin producing alga Haematococcus pluvialis was dried by spray- or
freeze-drying and under vacuum or air at -20 degrees C to 37 degrees C for
20weeks. Freeze-drying led to 41% higher astaxanthin recovery compared to
commonly-used spray-drying. Low storage temperature (-20 degrees C, 4 degrees C)
and vacuum-packing also showed higher astaxanthin stability with as little as
12.3+/-3.1% degradation during 20weeks of storage. Cost-benefit analysis showed
that freeze-drying followed by vacuum-packed storage at -20 degrees C can
generate AUD$600 higher profit compared to spray-drying from 100kgH. pluvialis
powder. Therefore, freeze-drying can be suggested as a mild and more profitable
method for ensuring longer shelf life of astaxanthin from H. pluvialis.
PMID- 28411990
TI - Qualitative and nutraceutical aspects of lemon fruits grown on the mountainsides
of the Mount Etna: A first step for a protected designation of origin or
protected geographical indication application of the brand name 'Limone
dell'Etna'.
AB - The cultivation of lemon (Citrus limon (L.) Burm f.) has occurred for centuries
at the mountainsides of the Mount Etna the largest active volcano in Europe
(Sicily, Italy). The peculiar geographical, soil and climatic conditions that
characterize this area have recently prompted citrus growers to launch the brand
name 'Limone dell'Etna' for the lemon fruits produced in that area. The present
research focused on evaluating the quality and nutraceutical properties of the
'Limone dell'Etna' fruit juice ('Primofiore', 'Bianchetto', and 'Verdello'
blooming) to enhance the value of a product that, due to its peculiar qualities,
could be awarded with one of the European certified labels protecting the lemon
geographical origin. Qualitative parameters, health-promoting components (such as
ascorbic acid, flavonoids, and hydroxycinnamic acids) and the in-vitro total
antioxidant capacity (ORAC, FCR) of fruit juice of two different varieties
('Femminello zagara bianca' and 'Monachello') were determined at fruit maturity.
The results showed that the Bianchetto and Verdello lemon fruit exhibited higher
levels of ascorbic acid than those recorded for the Primofiore production. The
amount of flavonoids in Verdello fruits of both cultivars was the highest, as was
reflected in the highest antioxidant activity. Thus, the 'Limone dell'Etna'
production, with particular reference to the Verdello fruit, must be considered
as a new, valuable and original source of natural antioxidants to be valorized
and even exploited in the processing industry.
PMID- 28411989
TI - Partridgeberry polyphenols protect primary cortical and hippocampal neurons
against beta-amyloid toxicity.
AB - beta-Amyloid (Abeta) deposition elicits a toxic effect on neurons and plays a
crucial role in the etiology and/or progression of Alzheimer's disease (AD).
Polyphenols found in fruits are endorsed for nutritional intervention in AD,
since they are known to have extensive therapeutic properties apropos of brain
health owing to their anti-oxidative effects against Abeta and neural reactive
oxygen species (ROS). The present study was aimed to investigate the
neuroprotective potential of polyphenols of partridgeberry (Vaccinium vitis-idaea
L.) and elucidate the mechanism by which they confer protection against Abeta
toxicity in rat primary neurons in vitro. The pre-treatment of rat primary
cortical and hippocampal neurons with partridgeberry polyphenols (10-200MUgmL-1)
significantly attenuated Abeta-induced cell death and membrane damage. The flavan
3-ol- and flavonol-rich fractions of the partridgeberry exhibited the strongest
ability to maintain cell viability (EC50 5.9MUgmL-1) and prevent lactose
dehydrogenase release (IC50 0.01MUgmL-1) (P<=0.05). Similar to the maintenance of
cellular viability, the flavan-3-ol- and flavonol-rich fractions also amplified
the greatest activity of SOD and catalase among all polyphenol preparations
exposed to neurons (P<=0.05). All four partridgeberry polyphenol preparations
reduced the intracellular Abeta levels by 7-15 folds, and initiated Abeta
clearance from neurons as compared to untreated cells (P<=0.05). Partridgeberry
derived polyphenol preparations; especially the flavonol-rich fraction (IC50
97.1MUgmL-1) significantly modulated the apoptotic targets and in vitro
acetylcholinesterase activity (P<=0.05), indicating potential pharmacotherapy
application in AD. Furthermore, the restoration of hyperactive caspases and Bcl2
family of apoptotic architects added to the neuroprotective candidacy of PPFs.
These findings suggest that partridgeberry polyphenols, especially flavan-3-ol-
and flavonol-rich fractions, could be of importance in prevention and/or
treatment of AD.
PMID- 28411991
TI - Effect of carrier oils on the physicochemical properties of orange oil beverage
emulsions.
AB - In this study, the effect of carrier oils on the physicochemical properties of
orange oil beverage emulsions was investigated. The beverage emulsions were
prepared by soybean soluble polysaccharides (SSPS) using a two-stage processing
of homogenization. Results showed that the presence of carrier oils could improve
the physical properties of beverage emulsions, including droplet size, size
distribution and turbidity, compared with only orange oil in oil phase of the
beverage emulsion. And the effect of long chain triglycerides on the physical
stabilities of beverage emulsions was significant (p<0.05) than that with medium
chain triglycerides (MCT). The oxidation rate of orange oil in the emulsion was
faster compared to that of the orange oil/carrier oils in emulsions. However, the
rheological properties of beverage emulsions were hardly dependent on the carrier
oils. In addition, all the emulsions exhibited near-Newtonian fluid behavior.
These findings revealed that the physicochemical properties of the beverage
emulsions could be effectively improved by the presence of carrier oils.
PMID- 28411992
TI - Improved oxidative barrier properties of emulsions stabilized by silica-polymer
microparticles for enhanced stability of encapsulants.
AB - The materials encapsulated within oil-in-water emulsions are prone to oxidation
due to the permeation of oxidative species across the oil-water interface and
into the lipid phase. Thus, the oxidative barrier properties of the interfacial
layer are pivotal in reducing oxidation within emulsified oils. To enhance these
barrier properties, we explored an approach of stabilizing emulsions using
'silica-polymer microparticles'. We hypothesize that these microparticles will
enhance the barrier properties of emulsion interfaces by mechanisms such as
higher interfacial thickness and quenching of oxidative species before they
permeate into the emulsions. Silica-epsilon-polylysine (Si-EPL) microparticles
were synthesized by electrostatic aggregation of anionic silica nanoparticles and
cationic epsilon-polylysine in the aqueous phase. Formation of Si-EPL
microparticles was validated using particle size, zeta-potential and scanning
electron microscopy measurements. These microparticles were subsequently used for
emulsion stabilization. Emulsions stabilized by silica nanoparticles alone were
used as control. Oxidative barrier properties were determined by measuring the
rate of permeation of peroxyl radicals from the aqueous to the oil phase of the
emulsion using fluorescence based methods. The rate of permeation of peroxyl
radicals was significantly lower in emulsions stabilized by Si-EPL microparticles
compared to that stabilized by silica nanoparticles. One of the mechanisms
responsible for the observed effect was enhanced quenching of peroxyl radical by
Si-EPL microparticles before they can permeate inside the oil phase. To further
validate the results, stability of a model bioactive compound, retinol,
encapsulated in these emulsions was compared. Consistent with peroxyl radical
permeation measurements, emulsion stabilized by Si-EPL microparticles
significantly improved the oxidative stability of retinol compared to that
stabilized by silica nanoparticles alone. Thus, by engineering the physical
properties of the interfacial layers, the oxidation of the encapsulants in
emulsions can be controlled.
PMID- 28411993
TI - Impact of irradiation and thermal processing on the immunochemical detection of
milk and egg allergens in foods.
AB - There is little information available on the antigenicity of allergens in foods
subjected to gamma irradiation and thermal processes. The objective of the study
was to evaluate the effects of gamma irradiation and thermal processing on the
recovery of milk and egg allergens in foods prepared using irradiated wheat flour
incurred with these allergens. Bread, boiled pasta and extruded cereal were
selected as food matrices for the study. Allergen detection was performed using
Surface Plasmon Resonance (SPR) and commercially available enzyme linked
immunosorbent assay (ELISA) kits. Protein structure was characterized using
differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)
spectroscopy, and circular dichroism (CD) spectroscopy. The ELISA kits performed
well in detecting allergens in the unprocessed flours with recoveries ranging
from 63-120%. The results for dough and uncooked pasta were similar to those of
unprocessed flours. Recoveries for boiled pasta were significantly (p<=0.05)
reduced. The lowest allergen recoveries were obtained in bread samples. Allergen
recoveries in gamma irradiated samples depended on the irradiation dose, the type
of ELISA kit used, the tested matrix, and the processing method. FTIR and CD
results showed that among the allergens casein was the most thermostable followed
by ovomucoid. beta-Lg and ovalbumin showed thermal sensitivity. In conclusion,
gamma irradiation may affect the antigenicity of allergenic food residues at low
levels depending on the food matrices and the processing methods.
PMID- 28411994
TI - Factors affecting the rheological properties of a structured cellular solid used
as a fat mimetic.
AB - The effects of water content, monoglyceride chain length and concentration, oil
type, and the addition of oil-phase and water-phase additives on the elastic
modulus and yield stress of a structured oil in water were evaluated. The goal
was to increase the elastic modulus of the original emulsion from 8.42*103+/
11.3Pa to 1.55*106+/-2.1*105Pa, and the yield stress from 112+/-2.31Pa to 835+/
227Pa. The addition of wax at greater than 10% (w/w), the use of palm oil or the
gelation of the liquid oil phase with 5-7.5% rice bran wax, the use of C-18
saturated monoglyceride at 6%(w/w), and 4% (w/w) for C-22 saturated monoglyceride
molecules were effective modifications capable of improving the mechanical
behavior of the emulsion so that it can be used as a zero trans and reduced
saturated fat laminating shortening substitute for puff pastry products.
PMID- 28411995
TI - The effect of in-amphorae aging on oenological parameters, phenolic profile and
volatile composition of Minutolo white wine.
AB - A wine was obtained from cryomacerated Minutolo grapes under reductive conditions
and aged for 12months in glass container and in 3 types of amphorae. After aging,
wines in glass containers showed the highest alcohol content, volatile acidity,
dissolved oxygen, concentrations of aromatics, alcohols, and esters and by the
lowest contents of enols and terpenes. They also showed the highest decrease of
flavonoids, hydroxycinnamoyl tartaric acids, and procyanidins. Wines in raw
amphorae showed the dramatic decrease of flavonoids and flavans reactive with
vanillin. The highest antioxidant activity was exhibited by wines in engobe
amphorae, while the lowest values were showed by the wines in glass containers
and glazed amphorae. Caftaric acid and procyanidin B3 decreased in wine aged
under glass while epicatechin mainly reduced in raw amphorae. According to the
Principal Component Analysis, the wines resulted homogeneously grouped as a
function of the type of container in which were aged.
PMID- 28411996
TI - Generation of volatile compounds in Brazilian low-sodium dry fermented sausages
containing blends of NaC1, KC1, and CaC12 during processing and storage.
AB - Brazilian dry fermented sausages with different salt contents were manufactured:
control (2.5% NaCl), 50% salt reduced (1.25% NaCl, F1), 50% replaced by KCl
(1.25% NaCl and 1.25% KCl, F2), 50% replaced by CaCl2 (1.25% NaCl and 1.25%
CaCl2, F3), and 50% replaced by KCl and CaCl2 (1.25% NaCl, 0.625% KCl and 0.625%
CaCl2, F4). Changes in the composition of volatile compounds were studied during
processing (0, 7, and 19days) and storage (30, 60, and 90days). Neither reduction
nor replacement of NaCl by KCI affected the volatile compounds produced during
the manufacturing process, and both increased the volatile compounds from
carbohydrate fermentation and amino acid degradation during storage. The addition
of CaCl2 improved the generation of hexanal and (E)-hept-2-enal and other
volatiles from lipid oxidation during processing and storage. After 90days of
storage, the control sample showed an increase in the generation of volatile
compounds from lipid oxidation.
PMID- 28411997
TI - Macromolecular antioxidants or non-extractable polyphenols in fruit and
vegetables: Intake in four European countries.
AB - Macromolecular antioxidants or non-extractable polyphenols are an emerging and
ignored fraction of dietary antioxidants that present differential structural and
physiological features as compared with the well-known extractable polyphenols.
In this study, the macromolecular antioxidant content and profile were determined
by the first time for the 24 most consumed fruit and vegetables in four European
countries (France, Germany, The Netherlands and Spain). Results showed that
macromolecular antioxidants, made up of hydolysable polyphenols and polymeric
proanthocyanidins, are major contributors (mean value 57%) to the total
polyphenol content of fruit and vegetables. Macromolecular antioxidant intake
from fruit and vegetable determined in the four countries selected was about
200mg. Spain had the highest daily per capita macromolecular antioxidant intake
from fruit, while The Netherlands had the highest intake derived from vegetables.
Future studies of plant food macromolecular antioxidant analysis and of dietary
intakes in different populations are needed to elucidate the contribution of
these macromolecular antioxidants to the health effects associated with fruit and
vegetable consumption, and with dietary antioxidant intake.
PMID- 28411998
TI - Social representations of safety in food services.
AB - This research aimed to evoke and analyze the perceptions of safe food through the
perspective of customers at two different food service settings in Sao Paulo,
Brazil. In-depth interviews (N=66) were conducted using a guide with open
questions focused on the individual's perceptions of safety, knowledge of food
borne diseases and self-involvement in the food chain. The Collective Subject
Discourse (CSD) technique, based on the Theory of Social Representations, was set
as the framework for the content analysis of the individual speeches with the aim
of writing a collective discourse representing the "voice of the customer".
Similarities and differences reflecting different socio-economic backgrounds came
up: in general, the interviewees showed concerns about hygiene and good practices
and recognized some food hazards, especially those of chemical and biological
natures. In situation of social vulnerability, some customers showed greater
concern with the guarantee of access to a substantial meal in face of economic
constraint. Finally, most customers reported a passive role in the food chain and
seemed to transfer to the restaurant staff the entire responsibility for the
safety of the meals served therein.
PMID- 28411999
TI - Impact of the industrial freezing process on selected vegetables - Part I.
Structure, texture and antioxidant capacity.
AB - In this work, the impact of the industrial freezing process on structure, texture
and total antioxidant capacity was studied using green asparagus stems, zucchini
and green beans. Samples were analysed as raw/uncooked, blanched, raw/boiled and
industrially frozen/boiled. A consistent damage of the vegetable tissue was
revealed by the histological analysis on vegetables boiled after freezing. The
cells appeared to be dehydrated, contracted and separated at different levels
depending on the anatomical structure of each vegetable. The initial textural
quality was partially retained in all blanched vegetables, and enhanced in cut
tested asparagus stems, in relation to the action of phenolic acids at cell wall
level. Raw/boiled and industrially frozen/boiled asparagus stems exhibited
comparable forces of penetration and cut tests. On the other hand, zucchini, both
raw and frozen, completely softened after boiling making the texture measurement
impossible. Industrially frozen/boiled green beans showed higher values of cut
and penetration forces, probably due to a higher presence of swollen cell walls,
in comparison to those raw/boiled. Blanching and boiling significantly increased
the ferric reducing antioxidant power values of asparagus stems and green beans
compared to uncooked/raw samples, while boiling after the freezing process
significantly deprived both vegetables of the initial antioxidant capacity. On
the other hand, boiling the frozen zucchini proved to be detrimental to the
antioxidant capacity. In conclusion, manufacturers and researchers should join
together to develop specific industrial freezing process conditions according to
the matrix of each vegetable.
PMID- 28412000
TI - Corrigendum to "Reliable estimation of dietary exposure to furan from coffee: An
automatic vending machine as a case study" [Food Research International 61 (2014)
257-263].
PMID- 28412001
TI - In vitro antioxidative and binding properties of phenolics in traditional, citrus
and exotic fruits.
AB - Many polyphenols bind proteins, therefore our research was focused on the
potential of protein binding to polyphenols of investigated fruits and their
health-related effects. The contents of polyphenols and related antioxidant
activities of traditional, citrus and exotic fruits were compared. The presence
of polyphenols (flavonoids and phenolic acids) in the investigated samples and
their interaction with human serum albumin (HSA) was studied by HPLC, Fourier
Transform Infrared (FT-IR) and three dimensional fluorescence spectroscopy (3D
FL). The highest levels of polyphenols, antioxidant and binding capacities were
found in red and blond grapefruits (citrus group), followed by strawberries and
apples (traditional group) and mangosteen and kiwi fruit (exotic fruit), which
also contained the highest levels of protocatechuic, p-coumaric, ferulic acids
and quercetin. In conclusion, for the first time, the interaction of the
polyphenols with human serum albumin was evaluated by fluorometry/FTIR. The
obtained binding profiles allowed the comparison of three different groups of
fruits. A mixture of these fruits can be recommended for consumption.
PMID- 28412002
TI - Yacon (Smallanthus sonchifolius) and Lactobacillus acidophilus CRL 1014 reduce
the early phases of colon carcinogenesis in male Wistar rats.
AB - The modifying effects of aqueous yacon extract (AYE) and Lactobacillus
acidophilus CRL 1014 against colon carcinogenesis induced by 1,2
dimethylhydrazine (DMH) in male Wistar rats were investigated. Animals were
allocated into five groups: G1: untreated group; G2: DMH-treated group; G3:
DMH+L. acidophilus-treated group; G4: DMH+AYE-treated group; G5: DMH+L.
acidophilus and AYE-treated group. A significant reduction (p<0.05) in leukocyte
DNA damage and in colonic cell proliferation was observed after the first DMH
administration in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups. In
this moment, a significant increase (p<0.05) in colonic apoptosis was also
observed in G3 (probiotic) and G5 (synbiotic) groups. In special, at five months
after DMH administrations, a significant reduction (p<0.05) in ACF development
was observed in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups.
Incidence of colon tumors was lower at five months in G4 (prebiotic) and G5
(synbiotic) groups but not in eight months after DMH administrations. In
conclusion, the findings suggest that the oral treatments have potential effects
as a chemopreventive agent against colon carcinogenesis on an early stage of
tumor development.
PMID- 28412003
TI - Preparation, physicochemical characterization and release behavior of the
inclusion complex of trans-anethole and beta-cyclodextrin.
AB - Trans-anethole (AT) has a variety of antimicrobial properties and is widely used
as food functional ingredient. However, the applications of AT are limited due to
its low water solubility, strong odor and low physicochemical stability.
Therefore, the aim of this work was to encapsulate AT with beta-cyclodextrin
(beta-CD) for obtaining inclusion complex by co-precipitation method. The
measurements effectively confirmed the formation of inclusion complex between AT
and beta-CD. The results showed that the inclusion complex presented new solid
crystalline phases and was more thermally stable than the physical mixture and
beta-CD. The phase solubility study showed that the aqueous solubility of AT was
increased by being included in beta-CD. The calculated stability constant of
inclusion complex was 1195M-1, indicating the strong interaction between AT and
beta-CD. Furthermore, the release study suggested that beta-CD provided the
protection for AT against evaporation. The release behavior of AT from the
inclusion complex was controlled.
PMID- 28412004
TI - The use of active PET to package rose wine: Changes of aromatic profile by
chemical evolution and by transfers.
AB - Active Polyethylene Terephthalate (PET) bottles containing 1 or 3% of oxygen
scavenger (named 1osPET and 3osPET) were used to pack rose wine. Changes in the
aromatic profiles were monitored during 12months and compared to those of a wine
packed in glass bottles. Wine in 1osPET bottles was differentiated from wine in
glass or 3osPET bottles by ten aging markers such as cis-dioxane, ethyl pyruvate
or furfural. Only trans-1,3-dioxolane allowed to discriminate wine in glass and
in 3osPET bottles. Methionol, an oxygen sensitive aroma compound, was preserved
in glass and 3osPET bottles but was slightly degraded (15%) in 1osPET bottles.
Chemical reactions were the main cause of the aroma compound degradation. Indeed,
the total amount of compounds sorbed only reached 160MUg considering the bottles
and the joint of cap after 12months of storage. The use of PET with 3% of oxygen
scavenger is adapted to pack wine for at least 12months.
PMID- 28412005
TI - Assessing of the potential of extruded flour paste as fat replacer in O/W
emulsion: A rheological and microstructural study.
AB - Extruded flour represents an economical and environmental friendly alternative as
fat replacer. In this research, the potential use of an extruded flour-water
paste as fat replacer in an oil-in-water emulsion was studied. The effect of
flour-water ratio and level of oil replacement (30, 50 and 70%) on the
microstructure, rheological properties and stability of mayonnaise-like emulsion
was evaluated. Fat replacement by extruded flour gradually increased the number
and reduced the size of oil droplets. All the emulsion samples showed a
pseudoplastic behaviour. At low shear rates a Newtonian region characterised by
Carreau model appeared (R2>0.99). In general, the limiting viscosity of the
Newtonian region and the consistency index increased with the decreased water
content of the paste and increased the level of oil substitution. A decrease in
oil concentration led to a greater thixotropic behaviour. Oscillatory test
revealed that predominance of the continuous or dispersed phase influenced
viscoelastic behaviour. Reduction in oil content resulted in an increased freeze
thaw stability. Results suggested that if the flour-water ratio of the paste is
controlled, extruded flour is appropriate for preparing reduced-fat oil-in-water
emulsion with similar rheological properties to the full fat and greater freeze
thaw stability.
PMID- 28412006
TI - Identification of potent antioxidant bioactive peptides from goat milk proteins.
AB - Goat milk proteins have gained increasing attention especially the bioactive
peptides released from the parent proteins by digestive enzymes. Specifically,
the interest in bioactives of goat milk is intensifying due to its reduced
allergenicity compared to bovine milk. In this study, proteins of goat milk were
fractionated into caseins (GCP) and whey proteins (GWP), hydrolyzed by pepsin and
the generated peptides were examined for radical scavenging activities. The
hydrolysates of whey (P-GWP) and casein (P-GCP) proteins exhibited potent
superoxide anion (O2?-) scavenging activity in a dose-dependent manner, as
investigated using the natural xanthine/xanthine oxidase (X/XOD) system. The P
GWP and P-GCP dramatically quenched the O2?- flux but had negligible effect on
the catalytic function of the enzyme, indicating specificity to scavenge O2?- but
not oxidase inhibition. Further, both P-GWP and P-GCP were able to remarkably
quench the chemical DPPH radical. Fractionation of hydrolysates by size-exclusion
chromatography produced four fractions (F1-F4) from both hydrolysates, with
variable O2?- scavenging activities. However, the slow eluting fractions (F4) of
both hydrolysates and fast eluting fraction (F2) of P-GCP contained peptides with
the highest scavenging activities. Peptides in the active fractions of P-GWP and
P-GCP, isolated by reversed phase-HPLC, exhibited significantly strong O2?-
scavenging activities. MALDI-TOF-MS allowed the identification of several
antioxidant peptides derived from both caseins and whey proteins, with beta
casein and beta-lactoglobulin being the major contributors, respectively. The
results demonstrate that digestion with pepsin generates multiple soluble
peptides from goat milk protein fractions with remarkable ability to scavenge
superoxide radicals and thus providing a fascinating opportunity for their
potential candidacy as antioxidant bioactive peptides.
PMID- 28412007
TI - Volatile profiles of healthy and aflatoxin contaminated pistachios.
AB - The volatile profile of four different groups of dried pistachios namely: H:
healthy, NC: naturally contaminated with aflatoxin, AC: artificially contaminated
with aflatoxigenic strains of the fungi Aspergillus flavus and ANT: artificially
contaminated with non-toxigenic strains of the fungi A. flavus, was determined.
The volatiles were isolated by the HS-SPME method and determined by GC-FID and GC
MS, whereas aflatoxin by HPLC. Seventy two volatile compounds were identified
almost equally distributed among the above four studied groups. The predominant
chemical compounds were monoterpenes, alcohols, ketones, aldehydes, esters and
hydrocarbons. The monoterpenes, mainly determined as alpha-pinene and alpha
terpinolene were detected in all samples. Even though the general volatile
profile was similar among groups, some differences were detected between healthy
and contaminated groups of samples. When some key volatiles such as eight-carbon
and seven-carbon alcohols and aldehydes were used along with the species-specific
sesquiterpenes and the other terpenes detected, a correct classification was
obtained in H, NC, AC and ANT groups, as was demonstrated by cluster and
discriminant analyses. This evidence provides a potential tool for distinguishing
contaminated samples on the basis of characteristic volatile patterns.
PMID- 28412008
TI - Temperature-dependent structure stability and in vitro release of chitosan-coated
curcumin liposome.
AB - Liposome, a promising delivery system with phospholipid bilayer, could improve
the water solubility of curcumin, which is a polyphenolic natural product with
many bioactivities. However, the instability of liposome limits its development
in application. In this study, the chitosan was used to protect the structure
stability of phospholipid bilayer of curcumin liposome and control the sustained
release rate of curcumin further. The temperature stability and phase transition
were studied by differential scanning calorimetry. When curcumin molecule was
embedded in phospholipid bilayer, the pre-transition temperature (50.40 degrees
C) and main phase transition temperature (61.47 degrees C) decreased about 10
degrees C compared to it without curcumin, and phospholipid bilayer fluidity was
increased. The pre-transition temperature was disappeared after chitosan coated
on the surface of curcumin liposome. The thermal stability test and X-ray
diffraction also indicate that high temperature could change the structure of
liposome and chitosan could protect the curcumin from damage and leak. The in
vitro release study showed that the cumulative release rate got faster with
temperature increased and chitosan could decrease the release rate. These results
may guide the potential application of chitosan-coated liposome as a carrier of
curcumin in nutraceutical and functional foods.
PMID- 28412009
TI - Shockwave lithotripsy with music: Less painful and more satisfactory treatment.
AB - INTRODUCTION: The objective of this study was to determine whether listening to
music during a session of extracorporeal shockwave lithotripsy (ESWL) improves
patients' pain. MATERIAL AND METHOD: A simple, blind randomisation was undertaken
of patients with kidney and ureter stones attending an ESWL session of 7,000
waves for the first time, between September and December 2014. One group was
given music and the other was not. The age, gender, location of stones
(kidney/ureter) were recorded and 2questionnaires: pre ESWL (questionnaire A) and
postESWL (questionnaire B). Each questionnaire contained a question about anxiety
and another question on pain on the Likert scale (0-10). Questionnaire B also had
a question on satisfaction and comfort (Likert 0-10). Other variables included
heart rate, respiratory rate, systolic and diastolic blood pressure on wave
2,000, 5,000 and 7,000, reason for halting the procedure, total pethidine (mg),
secondary analgesia, energy (J) and frequency (Hz). Bivariate analysis using the
Student's t-test, X2/Fisher test and a multiple linear regression model. RESULTS:
The sample comprised 95 patients, with a mean age of 52 (+/-13) years, 35
(36.84%) females, 60 (63.2%) males. A total of 25 (26.3%) ureter stones and 70
(73.7%) kidney stones. A number of 42 (44.2%) patients were given music. There
were no differences between the demographic variables or questionnaire A scores.
Satisfaction and pain were better on questionnaire B with music. CONCLUSION:
Music can reduce pain and improve patient satisfaction in ESWL treatment. More
studies are required to confirm this effect.
PMID- 28412010
TI - Assessment of impact of urbanisation on background radiation exposure and human
health risk estimation in Kuala Lumpur, Malaysia.
AB - Kuala Lumpur has been undergoing rapid urbanisation process, mainly in
infrastructure development. The opening of new township and residential in former
tin mining areas, particularly in the heavy mineral- or tin-bearing alluvial soil
in Kuala Lumpur, is a contentious subject in land-use regulation. Construction
practices, i.e. reclamation and dredging in these areas are potential to enhance
the radioactivity levels of soil and subsequently, increase the existing
background gamma radiation levels. This situation is worsened with the
utilisation of tin tailings as construction materials apart from unavoidable soil
pollutions due to naturally occurring radioactive materials in construction
materials, e.g. granitic aggregate, cement and red clay brick. This study was
conducted to assess the urbanisation impacts on background gamma radiation in
Kuala Lumpur. The study found that the mean value of measured dose rate was 251+/
6nGyh-1 (156-392nGyh-1) and 4 times higher than the world average value. High
radioactivity levels of 238U (95+/-12Bqkg-1), 232Th (191+/-23Bqkg-1,) and 40K
(727+/-130Bqkg-1) in soil were identified as the major source of high radiation
exposure. Based on statistical ANOVA, t-test, and analyses of cumulative
probability distribution, this study has statistically verified the dose
enhancements in the background radiation. The effective dose was estimated to be
0.31+/-0.01mSvy-1 per man. The recommended ICRP reference level (1-20mSvy-1) is
applicable to the involved existing exposure situation in this study. The
estimated effective dose in this study is lower than the ICRP reference level and
too low to cause deterministic radiation effects. Nevertheless based on
estimations of lifetime radiation exposure risks, this study found that there was
small probability for individual in Kuala Lumpur being diagnosed with cancer and
dying of cancer.
PMID- 28412011
TI - [Nicolau livedoid dermatitis with severe neurological involvement in a child].
AB - BACKGROUND: Nicolau syndrome is a rare condition consisting in tissue ischemia
and necrosis following intramuscular, intra-articular or subcutaneous injection.
PATIENTS AND METHODS: Immediately after gluteal intramuscular injection of
benzathine-penicillin, a 10-year-old male child presented an extensive painful
violaceous lesion on the left buttock associated with urinary incontinence and
left lower-limb paresis. Additional underlying muscular damage was supported by
high serum levels of creatine kinase and lactate dehydrogenase. Treatment was
based on fluid expansion, intravenous steroids and anticoagulants, resulting in
improvement of cutaneous and muscular lesions. Improvement in terms of
neurological dysfunction was obtained after regular neuromuscular rehabilitation.
DISCUSSION: This case underlines the need to prevent Nicolau syndrome by means of
compliance with the technical recommendations for intramuscular injections.
PMID- 28412012
TI - Preliminary results for interval feeding the orthogonal pressurized planar
electrochromatography system with sample solution for its preparative separation.
AB - The orthogonal pressurized planar electrochromatography (OPPEC) is an example of
2-D separation technique, in which two simultaneous and orthogonal processes of
electrophoresis and chromatography are involved in the separation mechanism. In
the case of preparative separation of substances characterized by different
electrophoretic mobility, such separation system can be constantly fed with the
sample solution and the separated components can be constantly collected at its
outlet. In the paper, as opposed to the previous studies, we discuss the
capabilities of OPPEC technique for preparative separation of substances
characterized by the same electrophoretic mobility. According to the proposed
solution, the separation system can be periodically fed with the sample solution
and separated components can be collected alternately at its outlet. The
advantages of this new approach over the column chromatography with regard to the
separation of complex mixtures have been signaled.
PMID- 28412013
TI - Investigation of the imaging characteristics of the ALBIRA II small animal PET
system for 18F, 68Ga and 64Cu.
AB - AIM: In this study the performance characteristics of the Albira II PET sub
system and the response of the system for the following radionuclides 18F, 68Ga
and 64Cu was analyzed. MATERIALS AND METHODS: The Albira II tri-modal system
(Bruker BioSpin MRI GmbH, Ettlingen, Germany) is a pre-clinical device for PET,
SPECT and CT. The PET sub-system uses single continuous crystal detectors of
lutetium yttrium orthosilicate (LYSO). The detector assembly consists of three
rings of 8 detector modules. The transaxial field of view (FOV) has a diameter of
80mm and the axial FOV is 148mm. A NEMA NU-4 image quality phantom (Data Spectrum
Corporation, Durham, USA) having five rods with diameters of 1, 2, 3, 4 and 5mm
and a uniform central region was used. Measurements with 18F, 68Ga and 64Cu were
performed in list mode acquisition over 10h. Data were reconstructed using a
maximum-likelihood expectation-maximization (MLEM) algorithm with iteration
numbers between 5 and 50. System sensitivity, count rate linearity, convergence
and recovery coefficients were analyzed. RESULTS: The sensitivities for the
entire FOV (non-NEMA method) for 18F, 68Ga and 64Cu were (3.78+/-0.05)%, (3.97+/
0.18)% and (3.79+/-0.37)%, respectively. The sensitivity based on the NEMA
protocol using the 22Na point source yielded (5.53+/-0.06)%. Dead-time corrected
true counts were linear for activities <=7MBq (18F and 68Ga) and <=17MBq (64Cu)
in the phantom. The radial, tangential and axial full widths at half maximum
(FWHMs) were 1.52, 1.47 and 1.48mm. Recovery coefficients for the uniform region
with a total activity of 8MBq in the phantom were (0.97+/-0.05), (0.98+/-0.06),
(0.98+/-0.06) for 18F, 68Ga and 64Cu, respectively. CONCLUSION: The Albira II pre
clinical PET system has an adequate sensitivity range and the system linearity is
suitable for the range of activities used for pre-clinical imaging. Overall, the
system showed a favorable image quality for pre-clinical applications.
PMID- 28412014
TI - Continuum-based DFN-consistent numerical framework for the simulation of oxygen
infiltration into fractured crystalline rocks.
AB - We present an enhanced continuum-based approach for the modelling of groundwater
flow coupled with reactive transport in crystalline fractured rocks. In the
proposed formulation, flow, transport and geochemical parameters are represented
onto a numerical grid using Discrete Fracture Network (DFN) derived parameters.
The geochemical reactions are further constrained by field observations of
mineral distribution. To illustrate how the approach can be used to include
physical and geochemical complexities into reactive transport calculations, we
have analysed the potential ingress of oxygenated glacial-meltwater in a
heterogeneous fractured rock using the Forsmark site (Sweden) as an example. The
results of high-performance reactive transport calculations show that, after a
quick oxygen penetration, steady state conditions are attained where abiotic
reactions (i.e. the dissolution of chlorite and the homogeneous oxidation of
aqueous iron(II) ions) counterbalance advective oxygen fluxes. The results show
that most of the chlorite becomes depleted in the highly conductive deformation
zones where higher mineral surface areas are available for reactions.
PMID- 28412015
TI - Managing sepsis: Electronic recognition, rapid response teams, and standardized
care save lives.
AB - PURPOSE: Sepsis can lead to poor outcomes when treatment is delayed or
inadequate. The purpose of this study was to evaluate outcomes after initiation
of a hospital-wide sepsis alert program. MATERIALS AND METHODS: Retrospective
review of patients >=18years treated for sepsis. RESULTS: There were 3917 sepsis
admissions: 1929 admissions before, and 1988 in the after phase. Mean age (57.3
vs. 57.1, p=0.94) and Charlson Comorbidity Scores (2.52 vs. 2.47, p=0.35) were
similar between groups. Multivariable analyses identified significant reductions
in the after phase for odds of death (OR 0.62, 95% CI 0.39-0.99, p=0.046), mean
intensive care unit LOS (2.12days before, 95%CI 1.97, 2.34; 1.95days after, 95%CI
1.75, 2.06; p<0.001), mean overall hospital LOS (11.7days before, 95% CI 10.9,
12.7days; 9.9days after, 95% CI 9.3, 10.6days, p<0.001), odds of mechanical
ventilation use (OR 0.62, 95% CI 0.39, 0.99, p=0.007), and total charges with a
savings of $7159 per sepsis admission (p=0.036). There was no reduction in
vasopressor use (OR 0.89, 95% CI 0.75, 0.1.06, p=0.18). CONCLUSION: A hospital
wide program utilizing electronic recognition and RRT intervention resulted in
improved outcomes in patients with sepsis.
PMID- 28412016
TI - Comment on, "On the influence of the electron dose-rate on the HRTEM image
contrast", by Juri Barthel, Markus Lentzen, Andreas Thust, ULTRAM12246 (2016),
http://dx.doi.org/10.1016/j.ultramic.2016.11.016.
PMID- 28412017
TI - The endocannabinoid system, a novel and key participant in acupuncture's multiple
beneficial effects.
AB - Acupuncture and its modified forms have been used to treat multiple medical
conditions, but whether the diverse effects of acupuncture are intrinsically
linked at the cellular and molecular level and how they might be connected have
yet to be determined. Recently, an emerging role for the endocannabinoid system
(ECS) in the regulation of a variety of physiological/pathological conditions has
been identified. Overlap between the biological and therapeutic effects induced
by ECS activation and acupuncture has facilitated investigations into the
participation of ECS in the acupuncture-induced beneficial effects, which have
shed light on the idea that the ECS may be a primary mediator and regulatory
factor of acupuncture's beneficial effects. This review seeks to provide a
comprehensive summary of the existing literature concerning the role of
endocannabinoid signaling in the various effects of acupuncture, and suggests a
novel notion that acupuncture may restore homeostasis under different
pathological conditions by regulating similar networks of signaling pathways,
resulting in the activation of different reaction cascades in specific tissues in
response to pathological insults.
PMID- 28412018
TI - Diffuse Carotid Arteriosclerosis and Stroke in a Patient With Schimke Immuno
osseous Dysplasia.
PMID- 28412019
TI - Renal function in relation to sodium intake: a quantitative review of the
literature.
AB - We undertook a quantitative literature review to search for evidence underpinning
current guidelines proposing a reduction of sodium intake to less than 2.4 g/d
for the management of chronic kidney disease. We searched PubMed for peer
reviewed articles published from January 1980 through May 2016. Two investigators
screened 5072 publications and extracted data from 36, including 11 cross
sectional and 5 longitudinal observational studies and 20 intervention trials.
Within-study effect sizes were pooled and standardized to a sodium gradient of
100 mmol/d by using inverse-variance weighted random effects models. Among cross
sectional studies, the pooled odds ratio for albuminuria was 1.23 (95% confidence
interval [CI], 0.92-1.64, P = 0.16), and the pooled mean difference in glomerular
filtration rate amounted to 8.5 ml/min (CI, -2.3 to 19.2 ml/min; P = 0.12). In
the cohort studies, the pooled relative risk of a renal endpoint was 1.08 (CI,
0.92-1.29; P = 0.35). In the intervention trials (median duration, 14 days
[range, 4-186 days]), the mean differences in estimated glomerular filtration
rate and albuminuria (high vs. low sodium intake) averaged 4.6 ml/min (CI, 3.4
5.8 ml/min; P < 0.0001) and 53% (CI, 21-84; P = 0.001), respectively. Cochran's Q
statistic indicated significant heterogeneity among cross-sectional studies for
both estimated glomerular filtration rate and albuminuria (P < 0.0001) and among
intervention trials for albuminuria (P = 0.04). In conclusion, there is no robust
evidence suggesting that long-term reduction of salt intake would prevent chronic
kidney disease or delay its progression. However, our current findings, which
were mainly obtained in people with slight renal impairment, cannot be
extrapolated to patients with moderate or severe chronic kidney disease.
PMID- 28412020
TI - Cardiac surgery in patients with congenital heart disease is associated with
acute kidney injury and the risk of chronic kidney disease.
AB - Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of
patients undergoing surgery for congenital heart disease. Here we determine if CS
AKI is associated with chronic kidney disease (CKD) in patients with congenital
heart disease. Using Danish regional population-based registries, our cohort
study included patients with congenital heart disease born between 1990-2010 with
first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in
and out-patient laboratory serum creatinine data, we identified individuals
fulfilling KDIGO stages of AKI within 5 days of cardiac surgery. A unique
personal identifier enabled unambiguous data linkage and virtually complete
follow-up. The cumulative incidences of CKD stages 2-5 according to presence of
CS-AKI were computed utilizing serum creatinine values and Pottel's formula.
Using Cox regression, the corresponding hazard ratios were computed, adjusting
for sex, age at first cardiac surgery, calendar period of surgery, and congenital
heart disease severity. Of 382 patients with congenital heart disease undergoing
cardiac surgery, 127 experienced CS-AKI within 5 days of surgery. Median follow
up was 4.9 years. The five-year cumulative incidence of CKD for patients with CS
AKI was 12% (95% confidence interval 7%-20%), significantly higher than the 3%
(1%-5%) for those without CS-AKI with a significant adjusted hazard ratio of 3.8
(1.4-10.4). Thus, CS-AKI in patients with congenital heart disease is common and
is associated with an increased risk for CKD.
PMID- 28412021
TI - Prediction and validation of the duration of hemodialysis sessions for the
treatment of acute ethylene glycol poisoning.
AB - The duration of hemodialysis (HD) sessions for the treatment of acute ethylene
glycol poisoning is dependent on concentration, the operational parameters used
during HD, and the presence and severity of metabolic acidosis. Ethylene glycol
assays are not readily available, potentially leading to undue extension or
premature termination of HD. We report a prediction model for the duration of
high-efficiency HD sessions based retrospectively on a cohort study of 26 cases
of acute ethylene glycol poisoning in 24 individuals treated by alcohol
dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD
for more than 14 days, and two died. In 19 cases, the mean ethylene glycol
elimination half-life during high-efficiency HD was 165 minutes (95% confidence
interval of 151-180 minutes). In a training set of 12 patients with acute
ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and
a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases
to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model
was then validated in a set of seven acute ethylene glycol poisonings. Thus, the
HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene
glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.
PMID- 28412022
TI - Acute kidney injury is associated with microvascular myocardial damage following
myocardial infarction.
AB - Acute kidney injury (AKI) is a frequent complication in patients with ST
elevation myocardial infarction (STEMI) treated by primary percutaneous coronary
intervention. However, the pathophysiology of AKI in this setting is complex and
goes beyond the administration of contrast media. Studies assessing the impact of
infarct characteristics on AKI are currently lacking. Therefore, we investigated
the association of AKI with myocardial as well as microvascular injury in an
initial total of 361 consecutive STEMI patients treated by primary percutaneous
coronary intervention. Of these, 318 patients were included in final analysis.
Serum creatinine was measured on admission as well as 24, 48, and 72 hours
thereafter with AKI defined as an increase in serum creatinine of 0.3 mg/dl or
more. Cardiac magnetic resonance (CMR) scans were performed in the first week
after infarction, with microvascular injury visualized by late gadolinium
enhancement CMR defined as any region of hypoenhancement within the hyperenhanced
area of infarction. Sixteen patients developed AKI. They showed significantly
lower left ventricular ejection fraction (45[interquartile range 40-52]% vs.
54[47-59]%), larger infarct size (21[15-35]% vs. 12[7-22]%) of left ventricular
myocardial mass, and more frequent microvascular injury (81 vs. 46%) than those
free of AKI. Meaningfully, in multivariate analysis including all CMR data,
microvascular injury was the sole independent predictor of AKI (odds ratio 6.74,
95% confidence interval of 1.49-30.43). Thus, among revascularized STEMI
patients, the presence of microvascular injury assessed by CMR was independently
associated with an increased risk of AKI. This suggests a potential
pathophysiological link between cardiac microvascular disease and renal injury
following STEMI.
PMID- 28412023
TI - Precise prediction of activators for the human constitutive androstane receptor
using structure-based three-dimensional quantitative structure-activity
relationship methods.
AB - The constitutive androstane receptor (CAR, NR1I3) regulates the expression of
numerous drug-metabolizing enzymes and transporters. The upregulation of various
enzymes, including CYP2B6, by CAR activators is a critical problem leading to
clinically severe drug-drug interactions (DDIs). To date, however, few effective
computational approaches for identifying CAR activators exist. In this study, we
aimed to develop three-dimensional quantitative structure-activity relationship
(3D-QSAR) models to predict the CAR activating potency of compounds emerging in
the drug-discovery process. Models were constructed using comparative molecular
field analysis (CoMFA) based on the molecular alignments of ligands binding to
CAR, which were obtained from ensemble ligand-docking using 28 compounds as a
training set. The CoMFA model, modified by adding a lipophilic parameter with
calculated logD7.4 (S+logD7.4), demonstrated statistically good predictive
ability (r2 = 0.99, q2 = 0.74). We also confirmed the excellent predictability of
the 3D-QSAR model for CAR activation (r2pred = 0.71) using seven compounds as a
test set for external validation. Collectively, our results indicate that the 3D
QSAR model developed in this study provides precise prediction of CAR activating
potency and, thus, should be useful for selecting drug candidates with minimized
DDI risk related to enzyme-induction in the early drug-discovery stage.
PMID- 28412024
TI - Prevalence of bacterial contamination in platelet concentrates at the National
Center of Blood Transfusion (Mexico).
AB - OBJECTIVES: Most common bacterial sepsis associated with transfusion is caused by
contaminated Platelet Concentrates (PC). The screening of PC to detect bacterial
contamination is obligatory in Mexico, and it is carried out in quality control
programs. In Mexico, the identification and molecular characterization of
bacterial contaminants to detect contamination sources have not been implemented
due to high costs; however, it is an actual current need. MATERIAL AND METHODS:
One hundred PC were randomly selected and microbiologically analyzed. This sample
size corresponds to 1% of the PC obtained by the National Center of Blood
Transfusion (NCBT) in Mexico City according to the Official Mexican Standard NOM
253-SSA1-2012. Additionally, molecular biology tests were implemented in order to
identify the possible contamination sources. RESULTS: Nine of the 100 PC analyzed
(9%) showed bacterial contamination; analysis of the nucleotide sequences
revealed the presence of characteristic microbiota from donor skin and soil.
Diverse clonal relationship between the strains was identified in Staphylococcus
epidermidis. CONCLUSION: Detection of contaminants associated with environmental
and skin flora, shows the need to implement measures in the process of
disinfecting skin at the site of phlebotomy and cleaning each of the areas
involved in blood collection.
PMID- 28412025
TI - The influence of chronic IL-6 exposure, in vivo, on rat Achilles tendon
extracellular matrix.
AB - When compared to placebo, acetaminophen (APAP) reduces tendon stiffness and
collagen cross-linking. APAP also enhances the exercise-induced increase in
peritendinous levels of IL-6. Elevated levels of IL-6 are associated with
tendinopathy, thus we hypothesized that chronic, elevated peritendinous IL-6
would alter tendon extracellular matrix (ECM). IL-6 (~3000pgml-1) was injected
(3dwk-1 for 8-wks) into the Achilles peritendinous region of male Wistar rats
(n=16) with the opposite leg serving as a sham. Fractional synthesis rates (FSR)
were determined using deuterium oxide. Collagen (hydroxyproline) and hydroxylysl
pyridinoline (HP) cross-linking were analyzed by HPLC. ECM and IL-6 related genes
were evaluated using qRT-PCR. Relative to sham, collagen (Col) 1a1 but not Col3a1
expression was suppressed (47%) in tendons exposed to IL-6 (p<0.05). Lysyl
oxidase (LOX) and MMP-1 expression were also reduced (37%) in IL-6 treated
tendons (p<0.05). Relative to sham the expression of MMP-2, -3, -9, and TIMP-1
were not altered by IL-6 treatment (p>0.05). Interleukin-6 receptor subunit beta
precursor (IL6st) was lower (16%) in IL-6 treated tendons when compared to sham
(p<0.05). Suppressor of cytokine signaling 3 (Socs3), signal transducer and
activator of transcription 3 (STAT3), and protein inhibitor of activated STAT 1
(Pias1) were not altered by IL-6 exposure (p>0.05). Neither collagen nor cross
linking content were altered by IL-6 (p>0.05). Additionally, IL-6 treatment did
not alter tendon FSR. Chronic treatment with physiologically relevant levels of
IL-6 suppresses expression of Col1a1 and LOX while also altering expression of
select MMPs but does not alter Achilles tendon collagen synthesis.
PMID- 28412026
TI - Primary bone sarcomas in patients over 40 years of age: A retrospective study
using data from the Bone Tumor Registry of Japan.
AB - BACKGROUND: Optimal treatments of patients aged >40 years with osteosarcoma and
Ewing sarcoma and of patients with other types of bone sarcoma have not yet been
established. METHODS: The clinical characteristics of 746 patients with primary
bone sarcomas aged >40 years listed in the nationwide tumor registry (Bone and
Soft Tissue Tumor Registry of Japan) were investigated. Patients with Ewing
sarcoma, conventional chondrosarcoma, multiple myeloma, and malignant lymphoma
were excluded. The effects of adjuvant chemotherapy were determined by comparing
outcomes in patients aged 40-70 years with non-metastatic high grade bone tumors
who received surgery plus chemotherapy with those who underwent surgery alone.
RESULTS: Axial site tumors (38.6%) and distant metastasis at presentation (21.4%)
were frequent in patients aged >40 years with primary bone sarcomas. Chemotherapy
was administered to 407 (54.6%) patients. Their 5-year overall survival (OS) and
progression free survival (PFS) rates were 47.6% and 39.8%, respectively.
Multivariate analysis showed that distant metastases at presentation,
histological high grade, and radiation therapy were significantly correlated with
both OS and PFS. Age and tumor size were also significantly correlated with OS.
Patients aged 40-70 years who underwent surgery plus chemotherapy and those who
underwent surgery alone had 5-year OS rates of 69.3% and 63.2%, respectively (p =
0.092), and 5-year PFS rates of 55.4% and 50.7%, respectively (p = 0.63).
CONCLUSIONS: Bone sarcoma patients aged >40 years had distinct clinical features
and a poor prognosis. Chemotherapy did not improve OS or PFS in patients aged 40
70 years.
PMID- 28412027
TI - Regionalization of radical cystectomy in the United States.
AB - PURPOSE: Radical cystectomy (RC) has become increasingly regionalized to high
volume hospitals. Our objective was to describe changes in regional market
concentration and the distribution of RCs among hospitals, and examine how these
changes affect patient travel distance to surgery. MATERIALS AND METHODS: We used
the surveillance, epidemiology, and end results-Medicare database to identify
patients who had RC for bladder cancer from 2001 to 2011. We defined RC market
concentration within each Hospital Referral Regions (HRR) in surveillance,
epidemiology, and end results using the Hirschman-Herfindhal Index. We measured
straight-line patient travel distance to the nearest cystectomy provider hospital
and used linear regression to evaluate the effect of market concentration on
travel distance for surgery. We performed a similar analysis on patients who had
laparoscopic cholecystectomy as a comparator. RESULTS: We identified 10,802
patients with bladder cancer who had RC. From 2001 to 2011, 40% of HRRs had a
statistically significant increase in Hirschman-Herfindhal Index, 53% had no
significant change and 7% had a statically significant decrease. The median
patient travel distance increased significantly from 10.4 miles (interquartile
range: 2.6-30.2) to 16 miles (interquartile range: 6.3-40.4, P<0.0001). Patients
who lived in a highly concentrated HRR had to travel significantly further than
patients who lived in an unconcentrated HRR (beta = 37.5, P<0.001). These trends
were not seen for laparoscopic cholecystectomy. CONCLUSIONS: Between 2001 and
2011, RC became increasingly regionalized to a small group of hospitals with a
resultant increase in regional RC market concentration and patient travel
distance. The clinical consequences on these changes to patients who require RC
are uncertain.
PMID- 28412028
TI - [Effectiveness of erlotinib in Critical Care Unit in patients with non-small cell
lung cancer with EGFR mutation].
AB - INTRODUCTION: The search for mutations epidermal growth factor receptor (EGFR)
has changed the therapeutic approach and prognosis of non-small cell lung cancer
(NSCLC). The effectiveness of tyrosine kinase inhibitors (TKI) has been
demonstrated orally in patients with EGFR mutation. We report the case of a
patient for whom treatment with TKI was started effectively in a Critical Care
Unit. OBSERVATION: A patient of 59 years is followed for a stage IV lung
adenocarcinoma with metastases in liver, brain, adrenal, lung and pleura. After a
first course of chemotherapy (cisplatin-gemcitabine), the patient presents a
multi-factorial acute respiratory distress. Due to an EGFR mutation, transfer to
intensive care is decided then orotracheal intubation with mechanical
ventilation. It is decided to initiate treatment with erlotinib via nasogastric
tube. The evolution will be marked by a tumor response leading to a favorable
issue. CONCLUSIONS: This case shows the value of initiate TKI despite
hospitalization in Intensive Care Unit and highlights the question of the
transfer in ICU patients with EGFR mutation.
PMID- 28412029
TI - What's in a side effect? The association between pulmonary vasodilator adverse
drug events and clinical outcomes in patients with pulmonary arterial
hypertension.
AB - BACKGROUND: Adverse drug events (ADEs) with pulmonary vasodilator use in
pulmonary arterial hypertension (PAH) are common. ADEs may contribute to worse
quality of life; however, their relationship to prognosis is unknown. The
objective of this study was to determine whether common ADEs after initiating
subcutaneous treprostinil were associated with prognosis in PAH. METHODS: We
assembled a retrospective cohort of participants from four clinical trials of
treprostinil for PAH, including 908 participants who received subcutaneous
treprostinil and 243 who received placebo at the time ADEs were ascertained. The
occurrences of four common early ADEs (infusion reactions, headaches, jaw pain,
or gastrointestinal side effects) were assessed during the eight weeks after
starting the infusion. We used Cox proportional hazards to estimate associations
between ADEs and mortality. RESULTS: No ADEs related to placebo were associated
with mortality. In participants who received treprostinil, infusion reactions,
headaches, and jaw pain were not associated with mortality. Gastrointestinal side
effects occurring during the first eight weeks following treprostinil infusion
were associated with a 57% increase in the hazard of mortality (95% CI: 14-118%).
This relationship was unchanged after adjusting for demographic differences and
differences in baseline PAH severity. CONCLUSIONS: Gastrointestinal ADEs after
starting subcutaneous treprostinil were associated with an increased risk for
mortality. Increased mortality was not observed with other early ADEs or with
gastrointestinal symptoms in participants who were not receiving treprostinil at
the time. This hypothesis-generating association suggests ADEs may identify
different phenotypes in PAH.
PMID- 28412030
TI - Simple quantification method for N-nitrosamines in atmospheric particulates based
on facile pretreatment and GC-MS/MS.
AB - Nine N-nitrosamines (i.e., N-nitrosomethylamine, N-nitrosodiethylamine (NDEA), N
nitrosodimethylamine (NDMA), N-nitrosodi-n-propylamine (NDPA), N
nitrosomorpholine (NMor), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine
(NPip), N-nitorosodi-n-butylamine (NDBA), and N-nitrosodiphenylamine (NDPhA) in
atmospheric PM2.5 collected in the fall season from an roadside site and a
residential in Seoul, Korea have been analyzed using a newly developed method
consisting of simple direct liquid extraction assisted by ultrasonication and
subsequent quantification using a gas chromatography-triple quadrupole mass
spectrometry (GC-TQMS). Excellent recovery values (92-100%) and method detection
limits for the target compounds atmospheric PM samples could be achieved even
without an evaporation step for sample concentration. The concentration of total
N-nitrosamines in PM2.5 was ranged from 0.3 to 9.4 ng m-3 in this study; NDMA,
NDEA, NDBA, NPyr, and NMor in PM2.5 were found to be the most frequently
encountered compounds at the sampling sites. Since no industrial plant is located
in Seoul, vehicle exhausts were considered major cause of the formation of
nitrosamines in this study. The mechanisms how these compounds are formed and
detected in the atmosphere are explained from the viewpoint of secondary organic
aerosol. Considering the concentrations of N-nitrosamines and their associated
potential health risks, a systematic monitoring of nitrosamines present in both
ambient air and PM2.5 including seasonal and diurnal variations of selected sites
(including potential precursor sources) should be carried out in the future. The
proposed sample pretreatment method along with the analytical method will
definitely help us perform the monitoring study.
PMID- 28412031
TI - Alterations in hyolaryngeal elevation after esophageal anastomosis: A possible
mechanism for airway aspiration.
AB - AIM: A prospective study was performed to evaluate anatomical alterations and
hyolaryngeal elevation (HE) by videofluoroscopic swallowing study (VFSS) in
patients with esophageal atresia-tracheoesophageal fistula (EA-TEF). METHODS:
Patients operated for EA-TEF were evaluated for age, sex, type of atresia and
time to esophageal anastomosis. All patients were evaluated by videofluoroscopic
swallowing study (VFSS). Penetration-Aspiration scale (PAS>=7 is considered as
aspiration), distance between upper esophageal sphincter and 2nd cervical
vertebrae (UES-C2) and hyolaryngeal elevation (HE) were evaluated by the same
deglutitionist who was blind to the study. The results of EA-TEF patients were
compared with healthy children. RESULTS: Eighteen patients with EA-TEF and 10
healthy controls were included. The median age was 16months (12-36m) in EA-TEF
and 18months (13-51m) in controls. Male-to-female ratio was 5:4 and 4:1
respectively. 12 of cases were isolated-EA, 1 of them was EA-proximal TEF and 5
of the cases were EA-distal TEF. Half of the cases had primary EAN and others
underwent delayed esophageal repair. Early oral feeding was also started in 9
patients (50%) whereas others had delayed oral feeding. VFSS showed aspiration in
27.7 (n=5) of cases (PAS>=7) in EA group. The median distance between UES-C2 was
3.04cm (min: 2.17-max: 3.94) in EA and 4.17cm (min: 3.45-max: 6.24cm) in
controls. Median distance for HE was 0.37cm (min: 0.18-max: 1.1cm) in EA and 1.15
(min: 0.61-max: 1.06cm) in controls. The distance between UES-C2 was
significantly lower than controls (p<0.05) and HE was decreased in EA-TEF without
any statistical significance. CONCLUSION: Children with EA-TEF had shortened
distance between airway and upper esophagus. HE may be inefficient to protect
airway during deglutition. Anatomical alterations after EAN suggest that airway
problems may be related with decreased HE in children with EATEF. LEVEL OF
EVIDENCE: Level II (Development of diagnostic criteria in a consecutive series of
patients and a universally applied "gold standard").
PMID- 28412032
TI - Upregulation of MiR-369-3p suppresses cell migration and proliferation by
targeting SOX4 in Hirschsprung's disease.
AB - BACKGROUND: Hirschsprung disease (HSCR) is a congenital digestive disease in the
new born. miR-369-3p has been reported to be involved in many human diseases.
However, the relationship between miR-369-3p and HSCR remains largely unknown.
METHODS: In this study, qRT-PCR was used to detect the relative expression of miR
369-3p in 60 HSCR bowel tissue samples and 47 matched controls. Bioinformatic
analysis and dual-luciferase reporter assay were performed to evaluate the target
for miR-369-3p. Cell Counting Kit-8 (CCK-8) assay, Transwell assay, wound healing
assay and flow cytometry were employed to investigate the biological function of
miR-369-3p in human SH-SY5Y and 293T cell lines. RESULTS: We found that ganglion
cell numbers were remarkably reduced while miR-369-3p was significantly
upregulated in HSCR tissues compared to that in adjacent normal tissues (P<0.01).
Dual-luciferase reporter assay showed that the 3'-UTR of SOX4 was a direct target
to miR-369-3p. Moreover, an increased level of miR-369-3p was inversely
correlated with decreased levels of SOX4 mRNA and protein (P<0.05, respectively).
Dysregulation of miR-369-3p and SOX4 significantly suppressed cell proliferation
and migration in SH-SY5Y and 293T cell lines in vitro (P<0.05, respectively).
CONCLUSION: Our study demonstrates that aberrant expression of miR-369-3p might
play a crucial role in the development HSCR by regulating SOX4 expression, which
may infer that it is an effective diagnostic target in the pathogenesis of HSCR,
but investigation is still needed to explore the underlying mechanism.
PMID- 28412033
TI - Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of
diabetic nephropathy in a mouse model of type 2 diabetes.
AB - AIMS: Vasopressin is increased in diabetes and was shown to contribute to
development of diabetic nephropathy through V2 receptor (V2R) activation in an
experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains
undocumented. This study addresses the issue in a mouse model of type 2 diabetes.
METHODS: Male obese diabetic db/db mice were treated for 12weeks with a selective
V2R antagonist (SR121463) and compared to non-treated db/db and non-diabetic db/m
mice. All animals were previously uninephrectomized. RESULTS: The V2R antagonist
did not alter glycemia or glycosuria in db/db mice. It induced a two-fold
increase in urine output and a 52% decrease in urine osmolality compared to non
treated db/db mice. After four weeks of treatment urinary albumin to creatinine
ratio was 50% lower in treated mice compared to non-treated mice, and remained
significantly lower until end of experiment. Glomerular filtration rate increased
significantly over time in non-treated db/db mice but remained stable in treated
mice. CONCLUSIONS: This study shows that vasopressin contributes to albuminuria
and glomerular hyperfiltration via V2R in a mouse model of type 2 diabetes. It
documents causality behind the association of vasopressin with renal disease
observed in diabetic patients.
PMID- 28412034
TI - Reply to: A systematic review of complications associated with direct implants
vs. tissue expanders following wise pattern skin-sparing mastectomy.
PMID- 28412035
TI - Novel Consequences of Bird Pollination for Plant Mating.
AB - Pollinator behaviour has profound effects on plant mating. Pollinators are
predicted to minimise energetic costs during foraging bouts by moving between
nearby flowers. However, a review of plant mating system studies reveals a
mismatch between behavioural predictions and pollen-mediated gene dispersal in
bird-pollinated plants. Paternal diversity of these plants is twice that of
plants pollinated solely by insects. Comparison with the behaviour of other
pollinator groups suggests that birds promote pollen dispersal through a
combination of high mobility, limited grooming, and intra- and interspecies
aggression. Future opportunities to test these predictions include seed paternity
assignment following pollinator exclusion experiments, single pollen grain
genotyping, new tracking technologies for small pollinators, and motion-triggered
cameras and ethological experimentation for quantifying pollinator behaviour.
PMID- 28412036
TI - RNA-Binding Proteins Revisited - The Emerging Arabidopsis mRNA Interactome.
AB - RNA-protein interaction is an important checkpoint to tune gene expression at the
RNA level. Global identification of proteins binding in vivo to mRNA has been
possible through interactome capture - where proteins are fixed to target RNAs by
UV crosslinking and purified through affinity capture of polyadenylated RNA. In
Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked
samples have been identified. As in mammals and yeast, the mRNA interactomes came
with a few surprises. For example, a plethora of the proteins caught on RNA had
not previously been linked to RNA-mediated processes, for example proteins of
intermediary metabolism. Thus, the studies provide unprecedented insights into
the composition of the mRNA interactome, highlighting the complexity of RNA
mediated processes.
PMID- 28412037
TI - Relationship between the degree of perineal trauma at vaginal birth and change in
haemoglobin concentration.
AB - BACKGROUND: Postpartum anaemia is a problem with high prevalence that
significantly affects maternal recovery. Among the causal factors is perineal
trauma. However, it is still not known what degree of perineal trauma produces a
greater reduction of haemoglobin. AIM: To assess the relationship between the
degree of perineal trauma and change in haemoglobin concentration at vaginal
birth. METHODS: An observational, analytical retrospective cohort study was
performed at the Mancha-Centro Hospital (Spain) during the period 2010-2014. Data
were collected regarding 3479 women who gave birth vaginally. The main outcome
variable was the change in haemoglobin concentration. Multivariate analysis by
means of multiple linear regression was performed to control possible confounding
factors and to determine the net effect of each degree of perineal trauma on
haemoglobin reduction. FINDINGS: Of the total sample, 20.1% of women (699) had an
intact perineum, 41.6% (1446) experienced some form of perineal trauma, but not
episiotomy, and the remaining 38.3% of women (1334) underwent an episiotomy. The
average reduction of haemoglobin was 1.46g/dL (Standard Deviation (SD)=1.09g/dL)
for women without episiotomy with a second degree tear and 2.07g/dL (SD=1.24g/dL)
for women who had an episiotomy and no perineal tear. The greatest reduction
occurred among women with episiotomy and a third or fourth degree tear with a
decrease of 3.10g/dL (SD=1.32g/dL). CONCLUSION: Episiotomy is related to greater
reduction of haemoglobin concentration in comparison with all degrees of
spontaneous perineal trauma. The use of episiotomy should be strictly limited.
PMID- 28412038
TI - Surgical treatment of postintubation tracheal stenosis: A retrospective 22
patient series from a single center.
AB - BACKGROUND/OBJECTIVE: We aimed to present cases of postintubation tracheal
stenosis (PITS), all due to long-term intubation and treated surgically in a
university hospital, and to discuss them in light of the literature. METHODS: In
this retrospective study, 22 patients who were treated with tracheal resection
and reconstruction due to PITS were included. Demographics, intubation
characteristics, localization of stenosis, surgical technique and material,
postoperative complications, and survival of patients were recorded. RESULTS: The
mean intubation duration was 16.95 days with a median of 15.00 days. Collar
incision was applied in 19 cases (86.4%); in two cases (9.1%) a median sternotomy
incision was used; and in the remaining case (4.5%), a right thoracotomy incision
was made. The mean tracheal stenosis length was 2.14 cm (mean excision length,
2.5 cm). In 17 cases (77.3%), the anterior walls were supported with vicryl
(polyglactin) suture one by one. No postoperative complications were observed in
12 cases (54.5%). No recurrence developed during the long-term follow-up of 15 of
the 22 patients (68.2%). Two patients (9.1%) died in the early stages after
surgery, and five patients (22.7%) had a stent inserted due to restenosis.
CONCLUSION: Tracheal resection and end-to-end anastomosis are the most efficient
techniques in cases without medical contraindications, despite emerging stent or
endoscopic procedures. Endoscopic interventions can be suggested as an
alternative to surgery in patients for whom surgery cannot be performed or who
develop recurrence.
PMID- 28412039
TI - Distal left main trifurcation disease in a patient with porcelain aorta.
AB - Coronary trifurcation lesions are a complex subset of lesions and are
substantially more complex than bifurcations when treated with percutaneous
coronary intervention (PCI) because of higher rates of acute periprocedural
complications (dissection, myocardial infarction, acute vessel closure) and less
effective long-term outcomes (stent thrombosis, restenosis) as compared to non
bifurcation lesions. We present the case of a 73-year-old man who was admitted to
our hospital with symptomatic severe aortic stenosis who was found to have a
distal left main trifurcation disease as well as porcelain aorta on work-up.
Given the high risk of stroke during surgical aortic valve replacement and
coronary artery bypass grafting, the patient was accepted by the heart team to
proceed with percutaneous coronary intervention (PCI) and trans-catheter aortic
valve replacement (TAVR). We describe a successful double mini-crush stenting
technique approach for this case.
PMID- 28412040
TI - ROS formation is a differential contributory factor to the fungicidal action of
Amphotericin B and Micafungin in Candida albicans.
AB - The hypothetical role played by the intracellular formation of reactive oxygen
species (ROS) in the fungicidal action carried out by Amphotericin B (AmB) and
Micafungin (MF) was examined in Candida albicans, which remains the most
prevalent fungal pathogen. The clinical MICs for MF and AmB were 0.016 and
0.12MUg/ml, respectively. Whereas AmB (0.5-1.0*MIC) induced a marked production
of intracellular ROS accompanied by a high degree of cell killing in the C.
albicans SC5314 strain, the fungicidal effect of MF was still operative, but ROS
generation was slight. Preincubation with thiourea suppressed the formation of
ROS and caused a marked increase in cell viability, regardless of the antifungal
used. Simultaneous measurement of several well established antioxidant enzymes
(catalase, glutathione reductase and superoxide dismutase) revealed strong AmB
induced activation of the three enzymatic activities, whereas MF only had a weak
stimulating effect. Likewise, AmB but not MF promoted a conspicuous rise in the
mitochondrial membrane potential together with the intracellular synthesis of
trehalose, the non-reducing disaccharide which acts as a specific protector
against oxidative stress in C. albicans. Optical and electronic microscopy
analysis revealed a significant damage to cell integrity and structural
alterations caused by both antifungals. Taken together, our results strongly
suggest that the induction of an internal oxidative stress in C. albicans through
the accumulation of ROS is a preferential contributory factor to the antifungal
action of a widely used polyene (AmB) but not of MF (echinocandin).
PMID- 28412042
TI - Targeting the Prostacyclin Pathway: Beyond Pulmonary Arterial Hypertension.
AB - Pioneering work demonstrated that an unstable substance isolated from rabbit and
pig aortas could relax arterial smooth muscle and inhibit platelet aggregation.
Since then, prostacyclin (prostaglandin I2, PGI2) and its analogs have raised
much pharmacological interest. In this review we detail how the PGI2 signaling
pathway is much more complex than was initially anticipated, involving peroxisome
proliferator-activated receptors (PPARs), prostaglandin transporters (PGTs), and
PGI2-thromboxane A2 (TXA2) receptor (IP TP) heterodimerization. We discuss the
distinct affinities of PGI2 analogs for prostanoid receptors. In addition, we
introduce the new direct and indirect pharmacological approaches to targeting the
PGI2 pathway within the systemic circulation, including non-prostanoid agonists
of the prostacyclin receptor (IP) and PGT inhibitors, as well as transcutaneous
pathways using iontophoresis and nanostructured lipid carriers.
PMID- 28412041
TI - Targeting Tyrosine Phosphatases: Time to End the Stigma.
AB - Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for
numerous cellular processes, and several PTPs have been validated as therapeutic
targets for human diseases. Historically, the development of drugs targeting PTPs
has been highly challenging, leading to stigmatization of these enzymes as
undruggable targets. Despite these difficulties, efforts to drug PTPs have
persisted, and recent years have seen an influx of new probes providing
opportunities for biological examination of old and new PTP targets. Here we
discuss progress towards drugging PTPs with special emphasis on the development
of selective probes with biological activity. We describe the development of new
small-molecule orthosteric, allosteric, and oligomerization-inhibiting PTP
inhibitors and discuss new studies targeting the receptor PTP (RPTP) subfamily
with biologics.
PMID- 28412043
TI - Assessment of high-priced systemic antifungal prescriptions.
AB - OBJECTIVES: To assess compliance with international guidelines for costly
antifungal prescriptions and to compare these results with a first study
performed in 2007. METHODS: Retrospective study including all costly antifungal
prescriptions made in surgical and medical intensive care units and in a
hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were
assessed in terms of indication, dosage, and antifungal de-escalation. RESULTS:
Seventy-four treatments were analyzed. Treatments were prescribed for
prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%).
Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%)
and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable
in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%,
and inappropriate in 23%. Prescriptions were inappropriate for the following
reasons: lack of dosage adjustment in light of the hepatic function (10 cases),
underdosage or excessive dosage by>25% of the recommended dose in seven cases. De
escalation to fluconazole was implemented in 40% of patients presenting with a
fluconazole-susceptible candidiasis. CONCLUSION: The overall incidence of
appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively,
P=0.004). Nevertheless, costly antifungal prescriptions need to be optimized in
particular for empirical therapy, dosage adjustment, and potential de-escalation
to fluconazole.
PMID- 28412044
TI - Guidelines on the management of infectious encephalitis in adults.
PMID- 28412045
TI - Transcranial direct current stimulation (tDCS) as a treatment for visual
hallucinations: A case study.
PMID- 28412046
TI - The epigenetic mechanism for discordance of autoimmunity in monozygotic twins.
AB - Monozygotic twins share an identical DNA sequence but are not truly "identical".
In fact, when it comes to health and disease, they may often display some level
of phenotypic discordance. The cause of this discordance is often unknown.
Epigenetic modifications such as DNA methylation, histone modification, and
microRNAs-mediated regulation regulate gene expression and are sensitive to
external stimuli. These modifications may be seen to bridge the gap between
genetics and the environment. Over the years, the importance of epigenetics as a
primary mechanism for the role that the environment plays in defining phenotype
has been increasingly appreciated. Mechanisms of epigenetics include DNA
methylation, histone modifications and microRNAs. Discordance rates in
monozygotic twins vary depending on the specific condition, from 11% in SLE to
64% in psoriasis and 77% in PBC. Other autoimmune diseases in which discordance
is found among monozygotic twins has also been studied include type 1 diabetes,
multiple sclerosis, rheumatoid arthritis, dermatomyositis and systemic sclerosis.
In some cases, the differences in various epigenetic modifications is slight,
even though the concordance rate is low, suggesting that epigenetics is not the
only factor that needs to be considered. Nonetheless, the study of phenotypic
discordance in monozygotic twins may shed light on the pathogenesis of autoimmune
diseases and contribute to the development of new methodologies for the diagnosis
and treatment of these diseases.
PMID- 28412047
TI - Patient-reported Quality of Life After Proton Beam Therapy for Prostate Cancer:
The Effect of Prostate Size.
AB - BACKGROUND: In the present study, we assessed the effect of prostate gland size
on patient-assessed genitourinary and gastrointestinal (GI) quality of life (QOL)
after definitive treatment of prostate adenocarcinoma with proton beam therapy.
PATIENTS AND METHODS: As a part of a prospective outcome tracking protocol, 81
patients treated at a single center between with proton beam therapy completed
the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before
treatment and at the follow-up examinations. We reviewed the dosimetric data,
reported as Vx (volume of organ receiving x Gy), and patient-reported QOL at 6
months. Genitourinary QOL was assessed using the American Urological Association
symptom score and EPIC urinary domain score. GI QOL was assessed using the EPIC
GI domain score. RESULTS: Larger prostate glands were associated with greater
bladder V70 (P < .01) and rectal V70 (P < .01). The rectal V70 was < 15% for all
patients (range, 4%-13.8%) with the planned treatment volume coverage (percentage
of the prescription dose covering 95% of the volume > 95%) maintained. Patients
with larger prostates did not have a greater change in their American Urological
Association symptom index scores (< 30 cm3, +2.3; 30-49 cm3, +3.2; >= 50 cm3,
0.2; P = .06) or urinary domain score (< 30 cm3, -3.6; 30-49 cm3, -3.1; >= 50
cm3, +3.8; P = .76) at 6 months after treatment. Also, prostate size was not
associated with a change in the EPIC GI domain score at 6 months after treatment
(< 30 cm3, -3.7; 30-49 cm3, -1.1; >= 50 cm3, -0.55; P = .67). CONCLUSION:
Definitive proton beam therapy for prostate cancer to a dose of 79.2 Gy resulted
in excellent patient-reported urinary and GI QOL, independently of the baseline
prostate size. This single-institution finding should be tested further in a
multi-institutional study to confirm the potential limited role of androgen
deprivation therapy.
PMID- 28412048
TI - Comparative proteome profiling of hydatid fluid from Algerian patients reveals
cyst location-related variation in Echinococcus granulosus.
AB - Human cystic echinococcosis, an endemic zoonosis in Algeria, is caused by larvae
of the cestode Echinococcus granulosus. Parasitic modulation of the immune
response allows E. granulosus to persist in intermediate hosts. Previous in vitro
and in vivo immunological studies have shown differences in host immune responses
according to the status and location of the hydatid cysts in the body. In this
study, a proteomic analysis of human hydatid fluids was performed to identify the
proteins in hydatid cyst fluids. Hydatid fluid was obtained after cystic surgical
removal from three patients with these cysts. The study was conducted on fertile
hydatid fluids from lungs, vertebra, and infertile paravertebral fluids.
Comparisons of the protein compositions of these fluids revealed differences in
their protein profiles. These differences are probably related to the cyst
location and fertility status of the parasite. Notably, our analysis identified
new proteins from the parasite and human host. The identification of host
proteins in hydatid fluids indicates that the hydatid walls are permeable
allowing a high protein exchange rate between the metacestode and the affected
tissue. Interestingly, our study also revealed that parasite antigenic protein
expression variations reflect the differences observed in host immunostimulation.
PMID- 28412050
TI - [The correlation among the Ramsay sedation scale, Richmond agitation sedation
scale and Riker sedation agitation scale during midazolam-remifentanil sedation].
AB - BACKGROUND AND OBJECTIVES: Sedative and analgesic treatment administered to
critically ill patients need to be regularly assessed to ensure that previously
stated goals are well achieved as the risk of complications of oversedation is
minimized. We revised and prospectively tested the Ramsay Sedation Scale (RSS)
for interrater reliability and compared it with the Riker Sedation-Agitation
Scale (RSAS) and the Richmond Agitation Sedation Scale (RASS) to test construct
validity during midazolam-remifentanil sedation. METHODS: A convenience sample of
ICU patients was simultaneously and independently examined by pairs of trained
evaluators by using the revised RSAS, RSS, and RASS. Ninety-two ICU patients were
examined a total of 276 times by evaluator pairs. RESULTS: The mean patient age
was 61.32+/-18.68years, 45,7% were female (n=42), 54.3% male (n=50). Their APACHE
values varied between 3 and 39 with an average of 13.27+/-7.86 and 75% of the
cases were under mechanical ventilation. When classified by using RSS (2.70+/
1.28), 10.9% were anxious or agitated (RSS1), 68.5% were calm (RSS 2-3), and
20.6% were sedated (RSS 4-6). When classified by using RASS (-0.64+/-1.58), 20.7%
were anxious or agitated (RASS+1 to +4), 63.0% were calm (RASS 0 to -2), and
16.3% were sedated (RASS -3 to -5). When classified by using RSAS (2.63+/-1.00),
12% were anxious or agitated (RSAS 5-7), 57.6% were calm (RSAS 4), and 30.4% were
sedated (RSAS 1-3). RSS was correlated with the RSAS (r=-0.656, p<0.001) and RASS
was correlated with the RSAS (r=0.565, p<0.001). RSS was highly correlated with
the RASS (r=-0.664, p<0.001). CONCLUSIONS: Ramsay is both reliable and valid
(high correlation with the RASS and RSAS scales) in assessing agitation and
sedation in adult ICU patients.
PMID- 28412049
TI - More Than a Destination: Contraceptive Decision Making as a Journey.
AB - BACKGROUND: Contraceptive use is widely recognized as a means of reducing adverse
health-related outcomes. However, dominant paradigms of contraceptive counseling
may rely on a narrow definition of "evidence" (i.e., scientifically accurate but
exclusive of individual women's experiences). Given increased enthusiasm for long
acting, reversible contraceptive methods, such paradigms may reinforce counseling
that overprivileges effectiveness, particularly for groups considered at high
risk of unintended pregnancy. This study investigates where and how women's
experiences fit into the definition of evidence these counseling protocols use.
METHODS: Using a qualitative approach, this analysis draws on semistructured
interviews with 38 young (ages 18-24) Black and Latina women. We use a
qualitative content analysis approach, with coding categories derived directly
from the textual data. FINDINGS: Our analysis suggests that contraceptive
decision making is an iterative, relational, reflective journey. Throughout
contraceptive histories, participants described experiences evolving to create a
foundation from which decision-making power was drawn. The same contraceptive
related decisions were revisited repeatedly, with knowledge accrued along the
way. The cumulative experience of using, assigning meanings to, and developing
values around contraception meant that young women experienced contraceptive
decision making as a dynamic process. IMPLICATIONS FOR PRACTICE: This journey
creates a rich body of evidence that informs contraceptive decision making. To
provide appropriate, acceptable, patient-centered family planning care, providers
must engage with evidence grounded in women's expertise on their contraceptive
use in addition to medically accurate data on method effectiveness, side effects,
and contraindications.
PMID- 28412051
TI - [Impact of postoperative cognitive decline in quality of life: a prospective
study].
AB - BACKGROUND: Regardless the progress in perioperative care postoperative cognitive
decline (PCD) has been accepted unequivocally as a significant and frequent
complication of surgery in older patients. The aim of this study was to evaluate
the incidence of postoperative cognitive decline and its influence on quality of
life three months after surgery. METHODS: Observational, prospective study in a
Post-Anesthesia Care Unit (PACU) in patients aged above 45 years, after elective
major surgery. Cognitive function was assessed with Montreal Cognitive Assessment
(MOCA); Quality of life (QoL) was assessed using SF-36 Health Survey (SF-36).
Assessments were performed preoperatively (T0) and 3 months after surgery (T3).
RESULTS: Forty-one patients were studied. The incidence of PCD 3 months after
surgery was 24%. At T3 MOCA scores were lower in patients with PCD (median 20 vs.
25, p=0.009). When comparing the median scores for each of SF-36 domains, there
were no differences between patients with and without PCD. In patients with PCD,
and comparing each of SF-36 domains obtained before and three months after
surgery, had similar scores for every of the 8 SF-36 areas while patients without
PCD had better scores for six domains. At T3 patients with PCD presented with
higher levels of dependency in personal activities of daily living (ADL).
CONCLUSION: Three months after surgery patients without PCD had significant
improvement in MOCA scores. Patients with PCD obtained no increase in SF-36
scores but patients without PCD improved in almost all SF-36 domains. Patients
with PCD presented higher rates of dependency in personal ADL after surgery.
PMID- 28412052
TI - [The relationship between preoperative anxiety levels and vasovagal incidents
during the administration of spinal anesthesia].
AB - BACKGROUND: It was aimed to investigate the relationship between preoperative
anxiety and vasovagal symptoms observed during the administration of spinal
anesthesia in patients undergoing surgery in the perianal and inguinal regions.
METHODS: The study included patients with planned surgery for inguinal hernia
repair, anal fissure, hemorrhoid and pilonidal sinus excision. The study included
a total of 210 patients of ASA I-II, aged 18-65 years. Patients were evaluated in
respect of demographic characteristics, smoking and alcohol consumption, ASA
grade and educational level. Correlations were evaluated between the number of
attempts at spinal anesthesia and anesthesia history with vasovagal symptoms and
educational level, gender, smoking and alcohol consumption and anesthesia history
with anxiety scores. The instant (transient) state anxiety inventory part of the
Transient State/Trait Anxiety Inventory (State Trait Anxiety Inventory - STAI)
was used to determine the anxiety levels of the participants. Clinical findings
of peripheral vasodilation, hypotension, bradycardia and asystole observed during
the administration of spinal anesthesia were recorded. RESULTS: Vasovagal
incidences during the administration of spinal anesthesia were seen to increase
in cases of high anxiety score, male gender, and an absence of anesthesia
history. Educational level and the number of spinal needle punctures were not
found to have any effect on vasovagal incidents. CONCLUSION: The determination of
causes triggering vasovagal incidents seen during the application of spinal
anesthesia, better patient information of regional anesthesia implementations and
anxiety relief with preoperative anxiolytic treatment will help to eliminate
potential vasovagal incidents.
PMID- 28412053
TI - [The prognostic value of cerebral oxygen saturation measurement for assessing
prognosis after cardiopulmonary resuscitation].
AB - BACKGROUND: Despite new improvements on cardiopulmonary resuscitation (CPR),
brain damage is very often after resuscitation. OBJECTIVE: To assess the
prognostic value of cerebral oxygen saturation measurement (rSO2) for assessing
prognosis on patients after cardiopulmonary resuscitation. DESIGN: Retrospective
analysis. MEASUREMENTS AND RESULTS: We analyzed 25 post-CPR patients (12 female
and 13 male). All the patients were cooled to a target temperature of 33-34
degrees C. The Glascow Coma Scale (GCS), Corneal Reflexes (CR), Pupillary
Reflexes (PR), arterial Base Excess (BE) and rSO2 measurements were taken on
admission. The rewarming GCS, CR, PR, BE and rSO2 measurements were made after
the patient's temperature reached 36 degrees C. RESULTS: In survivors, the
baseline rSO2 value was 67.5 (46-70) and the percent difference between baseline
and rewarming rSO2 value was 0.03 (0.014-0.435). In non-survivors, the baseline
rSO2 value was 30 (25-65) and the percent difference between baseline and
rewarming rSO2 value was 0.031 (-0.08 to -20). No statistical difference was
detected on percent changes between baseline and rewarming values of rSO2.
Statistically significant difference was detected between baseline and rewarming
GCS groups (p=0.004). No statistical difference was detected between GCS, CR, PR,
BE and rSO2 to determine the prognosis. CONCLUSION: Despite higher values of rSO2
on survivors than non-survivors, we found no statistically considerable
difference between groups on baseline and the rewarming rSO2 values. Since the
measurement is simple, and not affected by hypotension and hypothermia, the rSO2
may be a useful predictor for determining the prognosis after CPR.
PMID- 28412054
TI - Community pharmacy transition of care services and rural hospital readmissions: A
case study.
AB - OBJECTIVES: To explore community pharmacist involvement in the transition of care
(TOC) process for patients discharged with acute myocardial infarction (AMI),
heart failure (HF), pneumonia, chronic obstructive pulmonary disease (COPD), or
elective total hip or knee arthroplasty (THA/TKA). SETTING: Patients discharged
from a 60-bed acute care hospital located in rural Missouri were seen by a
community pharmacist in 2 independent community pharmacy locations. PRACTICE
INNOVATION: Patients admitted with 1 of the 5 qualifying conditions and
identifying the participating pharmacy as their primary pharmacy spoke with a
community pharmacist within 72 hours of discharge to complete a comprehensive
medication review. A follow-up telephone call occurred 7 days after the encounter
to evaluate for drug-related problems, adherence, and key information recalled
from the previous visit. A final telephone call occurred on the 30th day after
discharge to assess for hospital readmissions and emergency department (ED)
visits. EVALUATION: Number of patients readmitted or visiting the ED within 30
days after discharge. RESULTS: Of the 9 patients completing the study, none were
readmitted or visited the ED within 30 days after discharge. All of the
participants were satisfied with the care and education provided by pharmacists.
The majority of patients recalled points related to specific medication education
topics. Based on the adherence tool, 8 of the 9 study participants had at least 1
barrier to medication access or adherence that could lead to post-discharge
medication-related problems. CONCLUSION: Community pharmacist involvement in the
TOC process may help to prevent readmissions for patients with AMI, HF,
pneumonia, COPD, and elective THA/TKA. Patients are overall satisfied with
community pharmacist involvement as they move from inpatient care to home. In
addition, there are multiple barriers affecting access and adherence to
medication therapy while at home, providing opportunities for pharmacist
intervention and assistance.
PMID- 28412055
TI - Impact of an open enrollment service on costs for Medicare Part D beneficiaries.
AB - OBJECTIVE: The primary objective was to determine total estimated cost savings
based on a patient's current medication regimen after comparing available
Medicare Part D plans for the upcoming year by using a plan comparison platform.
The secondary objective was to determine patient-centered concerns when
considering a change in Part D plans. DESIGN: Review of an open enrollment
service that included a patient survey and a Part D plan comparison. SETTING:
This study took place at a single independent community pharmacy in northwest
Alabama. PARTICIPANTS: Fifty-four patients eligible for Medicare Part D were
included in this study. MAIN OUTCOME MEASURES: The study was a review of an open
enrollment service that aids Medicare beneficiaries in selecting a Part D plan
that best fits their needs. It included a patient survey and plan comparison
using a plan comparison platform, during the 2015 Medicare open enrollment period
(October 15 to December 7). The survey assessed patient demographics, pharmacy
preferences, and cost concerns. Survey data were used to aid in plan selection
and analysis to determine the most common patient-centered concerns when
considering a change in plans. RESULTS: During the open enrollment period, 54
patients compared Medicare Part D plans. The majority of participants were female
(57%) and ranged in age from 65-69 years (37%) to 70-74 years (25.9%). The
majority of patients reported a preference for independent pharmacies (92.6%).
Deductible (40.7%) was the biggest concern for patients when comparing the main
cost variables for medication insurance. The average total cost difference per
patient per year showed that each patient saved an average of $1166.46.
CONCLUSION: The analysis of an independent pharmacy's open enrollment service
determined that a plan comparison platform is a valuable tool in helping patients
to compare and select cost-effective Medicare Part D prescription plans and in
helping patients save money.
PMID- 28412056
TI - Biomolecules from olive pruning waste in Sierra Magina - Engaging the energy
transition by multi-actor and multidisciplinary analyses.
AB - The price volatility of fossil resources, the uncertainty of their long-term
availability and the environmental, climatic and societal problems posed by their
operation lead to the need of an energy transition enabling the development and
utilization of other alternative and sustainable resources. Acknowledging that
indirect land-use change can increase greenhouse gas emission, the European Union
(EU) has reshaped its biofuel policy. It has set criteria for sustainability to
ensure that the use of biofuels guarantees real carbon savings and protects
biodiversity. From a sustainability perspective, biofuels and bioliquids offer
indeed both advantages (e.g., more secure energy supply, emission reductions,
reduced air pollution and production of high added-value molecules) as well as
risks (monocultures, reduced biodiversity and even higher emissions through land
use change). Approaching economic, environmental and social sustainability at the
local level and in an integrated way should help to maximize benefits and
minimize risks. This approach has been adopted and is described in the present
work that combines chemical, biological, social and territorial studies on the
management of pruning waste residues from olive trees in the Sierra Magina in
Spain. The biological and social analyses helped to orientate the research
towards an attractive chemical process based on extraction and pyrolysis, in
which high added value molecules are recovered and in which the residual biochar
may be used as pathogen-free fertilizer. In this region where farmers face
declining economic margins, the new intended method may both solve greenhouse gas
emission problems and provide farmers with additional revenues and convenient
fertilizers. Further research with a larger partnership will consolidate the
results and tackle issues such as the logistics.
PMID- 28412057
TI - Chemical characterization of biochar and assessment of the nutrient dynamics by
means of preliminary plant growth tests.
AB - Biochar can be produced from several organic sources with varying nutrients and
metal concentrations. Four commercial grade biochars were evaluated as peat
substitute. Biochars were characterised for plant nutrients and for biological
stability. The results showed that there were negligible quantities of N and P
and generally high levels of K and high biological stability. When these
materials were mixed with peat at 10, 25 and 50% and nutrients were added to
bring them to the same level of nutrients as in fertilized peat, it was found
that biochar mixtures considerably reduced the levels of calcium chloride/DTPA
(CAT) extractable N (including nitrate), P, and electrical conductivity- greater
extent with higher rates of biochar addition except for K. The pH and K levels
were increased with biochar addition. The drop in EC has important implications
regarding the use of other materials used to dilute peat, for example, composted
green waste, the rate of dilution is limited due to high EC and biochar addition
gives the potential for higher peat dilution of these materials. Nitrate and
phosphorus are very vulnerable to leaching of these nutrients in the environment
in peat substrates and the binding of these by biochar has implication for
leaching and nutrient application strategy. Root development using Cress test and
tomato plant height and biomass using containers, were in some cases better than
peat indicating that biochar could be used to dilute peat e.g. for seedling
production where root development and rapid growth are very important.
Application of biochars resulted in a marked reduction of N (and P) in the plant.
There were significant correlation between CAT extractable N and P and
corresponding plant concentration, indicating the standard growing media test,
CAT, would be suitable for assessing the nutrient status of peat biochar mixes.
PMID- 28412058
TI - Functional Outcomes and Cam Recurrence After Arthroscopic Treatment of
Femoroacetabular Impingement in Adolescents.
AB - PURPOSE: To compare the functional outcomes after arthroscopic treatment of
femoroacetabular impingement (FAI) in adolescent patients and non-adolescent
patients, and to report on the rate of cam recurrence within 2 years after
femoral osteoplasty in a limited sample of the adolescent group. METHODS: From
2010 to 2014, patients younger than 18 years with symptomatic FAI (alpha angle
>50 degrees ) who underwent hip arthroscopy with minimum 2-year follow-up or
reoperation were identified. A group of non-adolescent patients with identical
inclusion criteria, except age of 18 years or older, was also identified for
comparison. In addition, a separate group of adolescent patients with 2-year
postoperative radiographs was reviewed for cam recurrence. Demographic data,
operative data, and radiographic and clinical outcomes (modified Harris Hip Score
[mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score
Sport-Specific Subscale [HOS-SSS], and International Hip Outcome Tool 33 [iHOT
33] score) were collected. RESULTS: We identified 34 adolescent patients (38
hips) with an average age of 16 years (range, 13-17 years). The mean clinical
follow-up period was 36.1 +/- 11.6 months (range, 24.1-71.7 months) and 29.6 +/-
2.4 months (range, 27.9-31.3 months) without and with reoperation, respectively.
A control group of 296 non-adolescent patients (306 hips), with a mean age of 31
years (range, 18-59 years), was identified as our non-adolescent group. The mean
clinical follow-up period was 34.1 +/- 11 months (range, 24.0-77.4 months) and
15.1 +/- 9.1 months (range, 3.6-34.6 months) without and with reoperation,
respectively. Significant improvement was noted in adolescents in the changes in
outcome scores (mHHS, 22.2 [95% confidence interval (CI), 15.4-29.0]; HOS-ADL,
18.6 [95% CI, 11.9-25.2]; HOS-SSS, 33.5 [95% CI, 24.5-42.5]; and iHOT-33 score,
30.5 [95% CI, 21.8-39.2]; P < .001). Similar improvements were observed in non
adolescents (mHHS, 21.0 [95% CI, 19.0-23.0]; HOS-ADL, 16.6 [95% CI, 14.6-18.6];
HOS-SSS, 30.1 [95% CI, 26.6-33.6]; and iHOT-33 score, 34.9 [95% CI, 31.5-38.3]; P
< .001). There was no evidence of a difference in follow-up survey scores between
groups (P > .203). Revision surgery was required in 2 adolescent hips (5.3% [95%
CI, 1.5%-17.3%]) and 19 non-adolescent hips (6.2% [95% CI, 4.0%-9.5%]). Minimum 2
year radiographs were available for review in 24 adolescent patients (30 hips).
The alpha angle (mean +/- standard deviation) was reduced from 55.4 degrees +/-
12.1 degrees preoperatively to 38.7 degrees +/- 4.9 degrees at 6 weeks
postoperatively (mean difference, -16.4 degrees [95% CI, -19.8 degrees to -12.9
degrees ]; P < .001). At 2 years, the alpha angle remained at 39.2 degrees +/-
11.2 degrees , which did not differ from 6-week measurements (mean difference,
0.5 degrees [95% CI, -2.9 degrees to 3.9 degrees ]; P = .784). There were no
cases of cam recurrence (0% [95% CI, 0%-11.4%]). CONCLUSIONS: Significant
improvement in clinical outcomes can be anticipated after arthroscopic treatment
of FAI in adolescents. From a limited sample of our adolescent population, the
risk of cam recurrence appears low; however, further follow-up is needed to
ensure this does not represent a biased sample of the initial population. LEVEL
OF EVIDENCE: Level III, retrospective comparative study.
PMID- 28412059
TI - A Systematic Review of Tennis Elbow Surgery: Open Versus Arthroscopic Versus
Percutaneous Release of the Common Extensor Origin.
AB - PURPOSE: To compare complications, function, pain, and patient satisfaction after
conventional open, percutaneous, or arthroscopic release of the extensor origin
for the treatment of lateral epicondylitis. METHODS: A thorough review of 4
databases-PubMed, EBSCOhost, CINAHL (Cumulative Index to Nursing and Allied
Health Literature) Plus, and Scopus-was performed to identify all studies that
addressed surgical management of lateral epicondylitis. We included (1) studies
published between 2000 and 2015 and (2) studies with clearly defined surgical
techniques. We excluded (1) non-English-language manuscripts, (2) isolated case
reports, (3) studies with fewer than 10 subjects, (4) animal studies, (5) studies
with additional adjunctive procedures aside from release of the extensor origin,
(6) clinical or systematic review manuscripts, (7) studies with a follow-up
period of 6 months or less, and (8) studies in which less than 80% of patients
completed follow-up. Each study was analyzed for complication rates, functional
outcomes, pain, and patient satisfaction. RESULTS: Thirty reports were identified
that included 848 open, 578 arthroscopic, and 178 percutaneous releases. Patients
within each release group had a similar age (46 years vs 46 years vs 48 years; P
= .9 and P = .4, respectively), whereas there was a longer follow-up time in
patients who underwent surgery by an open technique (49.4 months vs 42.6 months
vs 23 months, P < .001). There were no differences in complication rates among
these techniques (3.8% vs 2.9% vs 3.9%; P = .5 and P = .9, respectively).
However, open techniques were correlated with higher surgical-site infection
rates than arthroscopic techniques (0.7% vs 0%, P = .04). Mean Disabilities of
the Arm, Shoulder and Hand scores were substantially better with both open and
arthroscopic techniques than with percutaneous release (19.9 points vs 21.3
points vs 29 points, P < .001). In addition, there was less pain reported in the
arthroscopic and percutaneous release groups as opposed to their open
counterparts (1.9 points vs 1.4 points vs 1.3 points, P < .0001). There were no
differences among the techniques in patient satisfaction rate (93.7% vs 89% vs
88%; P = .08 and P = .07, respectively). CONCLUSIONS: Functional outcomes of open
and arthroscopic releases may be superior to those of percutaneous release. In
addition, patients may report less pain with arthroscopic and percutaneous
techniques. Although the risk of complications is similar regardless of
technique, patients may be counseled that their risk of infectious complications
may be slightly higher with open releases. However, it is important to note that
this statistical difference may not necessarily portend noticeable clinical
differences. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV
evidence.
PMID- 28412060
TI - Minimum 2-Year Outcomes of Arthroscopic Management of Symptomatic Hip Labrum
Tears in Patients With Global Acetabular Overcoverage.
AB - PURPOSE: To report minimum 2-year patient-reported outcomes (PROs) after hip
arthroscopy (HA) for symptomatic labral tears in patients with global acetabular
overcoverage. METHODS: This study was a retrospective case series of patients who
underwent HA from April 2008 to April 2013. The inclusion criteria were patients
with global acetabular overcoverage, defined as a lateral center-edge angle
greater than 40 degrees , and with coxa profunda, defined radiologically by the
ilioischial line lateral to the acetabular floor. Only patients with minimum 2
year follow-up and no history of hip conditions or surgery were included. We
recorded demographic, examination, radiologic, and intraoperative findings;
intraoperative procedures performed; and the following PROs: modified Harris Hip
Score (mHHS), Non-Arthritic Hip Score, Hip Outcome Score-Activities of Daily
Living (HOS-ADL), Hip Outcome Score-Sports-Specific Subscale (HOS-SSS), visual
analog scale, and patient satisfaction. RESULTS: The inclusion criteria were met
by 39 patients, of whom 35 (89.7%) had 2-year follow-up. There was no distinct
pattern of examination findings. The study population had a mean acetabular
inclination of -1.19 degrees and an anterior center-edge angle of 35 degrees .
There was no association with measures of acetabular retroversion. Intrasubstance
tearing of the labrum occurred in 75% of patients (mean tear size, 2.68 hours on
acetabular clock face; mean location, 11.5 to 3 on acetabular clock face). There
were significant improvements in the mean scores for all PROs: mHHS, 13.5 +/-
17.7 points (P < .01); Non-Arthritic Hip Score, 14.3 +/- 21.3 (P < .001); HOS
ADL, 11.6 +/- 19.7 (P < .001); HOS-SSS, 17.1 +/- 35.1 (P < .001); and visual
analog scale, -2.77 +/- 2.58 (P < .001). The mean patient satisfaction rating was
6.61. The improvements in mHHS, HOS-ADL, and HOS-SSS did not reach the minimal
clinically important difference. The incidence of secondary procedures was 17% (4
patients underwent conversion to total hip arthroplasty and 2 required revision
HA). CONCLUSIONS: HA in patients with global acetabular overcoverage was
associated with improvements in PROs and pain at minimum 2-year follow-up.
However, these improvements did not reach the minimal clinically important
difference for the mHHS, HOS-ADL, and HOS-SSS. The incidence of secondary
procedures was 17%. The pattern of labral injury is predominantly intrasubstance
labral damage with a narrow rim of adjacent chondral injury. LEVEL OF EVIDENCE:
Level IV, therapeutic case series.
PMID- 28412061
TI - Influence of the Labrum on Version and Diameter of the Glenoid: A Morphometric
Study Using Magnetic Resonance Images.
AB - PURPOSE: To use magnetic resonance imaging to determine the influence of the
labrum on both the osseous version and effective diameter of the glenoid.
METHODS: This was a retrospective, cross-sectional study of patients with
shoulder pain who underwent MRI between February 2014 and February 2015. The
morphology of the glenoid labrum and glenoid was scanned with a 3-T magnetic
resonance imaging scanner, and variables were measured by use of IntelliSpace
PACS Enterprise. Patients were included if they were aged between 18 and 40 years
and the radiologist reported a normal glenohumeral joint or if they were young
patients aged less than 30 years with acute traumatic isolated partial- or full
thickness tears of the rotator cuff with a history of symptoms of less than 3
months. A pilot study was conducted with 3 observers and 3 repeated measurements
at intervals to determine the interobserver and intraobserver reliability. Data
analysis included descriptive statistics of measured variables, as well as paired
Student t tests to determine the relative difference between labral and osseous
morphometric variables. RESULTS: Excellent inter-rater reliability (0.95-0.96)
and intrarater reliability (0.93-0.98) were obtained in the pilot study of 20
patients. The study population was composed of 100 patients with a mean age of
37.3 years (standard deviation [SD], 11.8 years), having a gender distribution of
56 male and 44 female patients; there were 53 right and 47 left shoulders. The
glenoid osseous version measured -5.7 degrees (SD, 5.3 degrees ), and the labral
version measured -10 degrees (SD, 5.5 degrees ); the glenoid osseous diameter
measured 28.0 mm (SD, 3.3 mm), and the labral diameter measured 31.9 mm (SD, 3.2
mm). The labrum significantly increased the version by 4.3 degrees (P = .001)
and significantly increased the diameter by 3.9 mm (P = .001). CONCLUSIONS: The
results of this study showed that the labrum increased the effective glenoid
version by 75% (4.3 degrees of retroversion) and the effective glenoid diameter
by 14% (3.9 mm). LEVEL OF EVIDENCE: Level IV, prognostic case series.
PMID- 28412062
TI - Development and Internal Validation of a Novel Model to Identify the Candidates
for Extended Pelvic Lymph Node Dissection in Prostate Cancer.
AB - BACKGROUND: Preoperative assessment of the risk of lymph node invasion (LNI) is
mandatory to identify prostate cancer (PCa) patients who should receive an
extended pelvic lymph node dissection (ePLND). OBJECTIVE: To update a nomogram
predicting LNI in contemporary PCa patients with detailed biopsy reports. DESIGN,
SETTING, AND PARTICIPANTS: Overall, 681 patients with detailed biopsy
information, evaluated by a high-volume uropathologist, treated with radical
prostatectomy and ePLND between 2011 and 2016 were identified. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariable logistic regression model
predicting LNI was fitted and represented the basis for a coefficient-based
nomogram. The model was evaluated using the receiver operating characteristic
derived area under the curve (AUC), calibration plot, and decision-curve analyses
(DCAs). RESULTS AND LIMITATIONS: The median number of nodes removed was 16.
Overall, 79 (12%) patients had LNI. A multivariable model that included prostate
specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores
with highest-grade PCa, and percentage of cores with lower-grade disease
represented the basis for the nomogram. After cross validation, the predictive
accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated
improved risk prediction against threshold probabilities of LNI <=20%. Using a
cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven
(1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering
Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs
89.5%), better calibration characteristics, and a higher net benefit at DCA.
CONCLUSIONS: An ePLND should be avoided in patients with detailed biopsy
information and a risk of nodal involvement below 7%, in order to spare
approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. PATIENT SUMMARY:
We developed a novel nomogram to predict lymph node invasion (LNI) in patients
with clinically localized prostate cancer based on detailed biopsy reports. A
lymph node dissection exclusively in men with a risk of LNI >7% according to this
model would significantly reduce the number of unnecessary pelvic nodal
dissections with a risk of missing only 1.5% of patients with LNI.
PMID- 28412063
TI - Diagnostic Performance of Magnetic Resonance Imaging for the Detection of Bone
Metastasis in Prostate Cancer: A Systematic Review and Meta-analysis.
AB - CONTEXT: Magnetic resonance imaging (MRI) has been tested for detecting bone
metastasis and has shown promising results. Yet, consensus has not been reached
regarding whether it can replace the role of bone scintigraphy in this clinical
setting or not. OBJECTIVE: To review the diagnostic performance of contemporary
(>=1.5 T) MRI for the detection of bone metastasis in patients with prostate
cancer. EVIDENCE ACQUISITION: MEDLINE and EMBASE were searched up to January 22,
2017. We included studies that used MRI using >=1.5-T scanners for the detection
of bone metastasis in patients with prostate cancer, using histopathology or best
value comparator as the reference standard. Two independent reviewers assessed
the methodological quality using the Quality Assessment of Diagnostic Accuracy
Studies-2 tool. Per-patient sensitivity and specificity of included studies were
calculated, and pooled and plotted in a hierarchical summary receiver operating
characteristic plot. Meta-regression and sensitivity analyses were performed.
EVIDENCE SYNTHESIS: Ten studies (1031 patients) were included. Pooled sensitivity
was 0.96 (95% confidence interval [CI] 0.87-0.99) with a specificity of 0.98 (95%
CI 0.93-0.99). At meta-regression analysis, only the number of imaging planes
(>=2 vs 1) was a significant factor affecting heterogeneity (p<0.01). Sensitivity
analyses showed that specificity estimates were comparable and consistently high
across all subgroups, but sensitivity estimates demonstrated some differences.
Studies using two or more planes (n=4) had the highest sensitivity (0.99 [95% CI
0.98-1.00]). CONCLUSIONS: Contemporary MRI shows excellent sensitivity and
specificity for detection of bone metastasis in patients with prostate cancer.
Using two or more imaging planes may further improve sensitivity. However,
caution is needed in applying our results due to the heterogeneity among the
included studies. PATIENT SUMMARY: We reviewed studies using contemporary
magnetic resonance imaging (MRI) for the detection of bone metastasis in prostate
cancer patients. MRI shows excellent diagnostic performance in finding patients
with bone metastasis.
PMID- 28412064
TI - Re: Diagnostic Accuracy of Multi-parametric Magnetic Resonance Imaging and
Transrectal Ultrasound Biopsy in Prostate Cancer (PROMIS): A Paired Validating
Confirmatory Study.
PMID- 28412065
TI - Comparative Effectiveness of Trimodal Therapy Versus Radical Cystectomy for
Localized Muscle-invasive Urothelial Carcinoma of the Bladder.
AB - : Given the lack of randomized evidence comparing trimodal therapy (TMT) to
radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder
(UCB), we performed an observational cohort study to examine the comparative
effectiveness of these two definitive treatments. Within the National Cancer Data
Base (2004-2011),we identified 1257 (9.8%) and 11 586 (90.2%) patients who
received TMT and RC, respectively. Inverse probability of treatment weighting
(IPTW)-adjusted Kaplan-Meier analysis showed that median overall survival (OS)
was similar between the TMT (40 mo, 95% confidence interval [CI] 34-46) and RC
groups (43 mo 95% CI 41-45; p=0.3). In IPTW-adjusted Cox regression analysis with
a time-varying covariate, TMT was associated with a significant adverse impact on
long-term OS (hazard ratio 1.37, 95% CI 1.16-1.59; p<0.001). Interaction terms
indicated that the adverse treatment effect of TMT versus RC decreased with age
(p=0.004), while there was no significant interaction with gender (p=0.6),
Charlson comorbidity index (p=0.09) or cT stage (p=0.8). In conclusion, we found
that TMT was generally associated with worse long-term OS compared to RC for
muscle-invasive UCB. However, the survival benefit of RC should be weighed
against the risks of surgery, especially in older patients. These results are
preliminary and emphasize the need for a randomized controlled trial to compare
TMT versus RC. PATIENT SUMMARY: We examined the comparative effectiveness of
trimodal therapy versus radical cystectomy for muscle-invasive urothelial
carcinoma of the bladder. We found that trimodal therapy was generally associated
with worse long-term overall survival, although there may be no difference with
radical cystectomy in older individuals.
PMID- 28412066
TI - Ranibizumab Injection as Primary Treatment in Patients with Retinopathy of
Prematurity: Anatomic Outcomes and Influencing Factors.
AB - PURPOSE: To investigate the anatomic outcomes and influencing factors of
ranibizumab in the treatment of retinopathy of prematurity (ROP). DESIGN:
Retrospective case series. PARTICIPANTS: A total of 283 eyes of 145 patients with
type 1 ROP treated with intravitreal injection of ranibizumab (IVR) as primary
treatment. METHODS: Retrospective review of infants who were diagnosed with type
1 ROP and accepted IVR (0.25 mg/0.025 ml) as primary treatment from January 2012
to August 2015. The anatomic outcomes and the influencing factors were analyzed.
MAIN OUTCOME MEASURES: Anatomic outcomes of ROP eyes after IVR and the
influencing factors. RESULTS: A total of 283 eyes of 145 patients were included
in this study. There were a total of 266 eyes (94.0%) in the positive response
group and 17 eyes (6.0%) in the negative/no response group after IVR. Within the
positive response group, 139 eyes (48.6%) were in the regression without
reactivation subgroup, and 127 eyes (44.9%) were in the regression with
reactivation subgroup. A total of 152 eyes received additional laser or surgical
treatment. At the last visit, 278 eyes (98.2%) had attached retinas, and 5 eyes
(1.8%) had retinal detachment. A classification tree model showed that for
patients with gestational age (GA) <=29.5 weeks, the possibility of experiencing
reactivation after IVR is higher than that of those with GA >29.5 weeks (61.6%
vs. 29.6%). Moreover, for patients with GA <=29.5 weeks, those diagnosed with
zone II stage 2+ ROP have a lower possibility of experiencing reactivation than
other patients (37.9% vs. 80%). CONCLUSIONS: Intravitreal injection of
ranibizumab seemed to be effective in treating patients with ROP. After
treatment, there were primarily 3 different outcomes. Our predictive tree model
is helpful for ophthalmologists to evaluate the risk of reactivation.
PMID- 28412067
TI - Trend-based Analysis of Ganglion Cell-Inner Plexiform Layer Thickness Changes on
Optical Coherence Tomography in Glaucoma Progression.
AB - PURPOSE: To evaluate the rate of thinning in ganglion cell-inner plexiform layer
(GCIPL) thickness by optical coherence tomography (OCT) in glaucomatous eyes and
to use a trend-based approach to determine its diagnostic ability for detecting
glaucoma progression. DESIGN: Prospective, observational study. PARTICIPANTS:
Sixty-five patients with primary open-angle glaucoma with a minimum 3-year follow
up involving serial spectral-domain OCT measurement of GCIPL thickness. METHODS:
Patients were divided into a nonprogressor group (n = 38) and a progressor group
(n = 27) on the basis of serial red-free photography or visual field tests. The
rates of GCIPL thinning in the global region, affected hemifield, and 6 macular
sectors, and the minimum thickness, were determined by linear regression and
compared between groups. The area under the receiver operating characteristic
curves (AUCs) were calculated for each parameter. The GCIPL thinning rates were
compared between affected hemifields and unaffected hemifields. MAIN OUTCOME
MEASURES: The macular GCIPL thinning rates in the progressor and nonprogressor
groups and the ability of the GCIPL thinning rate to diagnose glaucoma
progression. RESULTS: The GCIPL thinning rate was significantly faster in
progressors than in nonprogressors in the global area (P < 0.001); in the
affected hemifield (P = 0.001); in the temporal, vertical, and nasal sectors of
the affected hemifield (P = 0.017, 0.032, and 0.030, respectively); and in the
minimum GCIPL thickness (P < 0.001). In the temporal sectors, the GCIPL thinning
rates were significantly faster in the affected than in the unaffected hemifield
(P = 0.013). The best GCIPL parameters were the global (AUC = 0.791), minimum
(AUC = 0.755), inferior hemifield (AUC = 0.708), and affected hemifield (AUC =
0.702) thinning rates. The global circumpapillary retinal nerve fiber layer
thinning rate correlated significantly with the global and inferotemporal sector
GCIPL thinning rates (rho = 0.259 and 0.366, respectively). CONCLUSIONS: The
GCIPL thinning rate on OCT was significantly faster for patients with glaucoma
with progression than for those without progression. The GCIPL thinning rate of
the temporal sector was faster in the affected than in the unaffected hemifield,
suggesting that the glaucomatous damage may progress locally in a specific
sequence. Trend-based analysis of GCIPL thickness on OCT may be useful for
assessing glaucoma progression objectively and quantitatively.
PMID- 28412068
TI - Vitreous Amyloidosis: Ocular, Systemic, and Genetic Insights.
AB - PURPOSE: To report the unique clinical and surgical characteristics encountered
in eyes with vitreous amyloidosis. Systemic evaluation and visual outcome after
vitrectomy are discussed. A novel mutation in the transthyretin gene (TTR) in
Indian patients with familial amyloid polyneuropathy (FAP) is described. DESIGN:
Retrospective, observational study. PARTICIPANTS: Ten eyes of 5 patients from 2
pedigrees with a diagnosis of vitreous amyloidosis. METHODS: Detailed history,
pedigree charting, systemic and ocular examination of 10 eyes (5 patients from 2
pedigrees) were carried out. Tests were performed to rule out vitreitis, retinal
vasculitis, vitreous hemorrhage, and systemic amyloidosis. Genetic analysis to
identify the mutation was performed in 1 patient. Vitreous biopsy, followed by 25
gauge pars plana vitrectomy, was performed in the same sitting in all cases.
Samples were sent for Congo red staining and polarized microscopy. Patients were
followed up on days 1, 7, and 28 and then every 2 months. Visual acuity
assessment, intraocular pressure measurement, and fundus examination were
performed each time. MAIN OUTCOME MEASURES: Mutations in TTR and postoperative
visual acuity. RESULTS: Mean age at presentation was 32 years, with a 3:2 male-to
female distribution. Family history was positive in all patients. Nine eyes had
pseudopodia lentis, whereas all 10 had glass wool-like vitreous. Glaucoma
developed in 1 patient (2 eyes). Waxy paper-like vitreous with firm vitreous
adhesions beyond major arcades and along retinal vessels was noted during surgery
in all eyes. Congo red staining and apple green birefringence demonstrated
vitreous amyloidosis. The mean preoperative best-corrected visual acuity (BCVA)
was 1.39+/-0.64 logarithm of the minimum angle of resolution (logMAR), whereas
the postoperative BCVA improved to 0.17+/-0.07 logMAR (P = 0.004). Gene
sequencing revealed a phenylalanine->isoleucine mutation in the 33rd position of
exon 2 of TTR in 1 patient of 1 pedigree, confirming the diagnosis of FAP. Two
patients subsequently were found to have sensorimotor autonomic neuropathy,
whereas 2 others had subclinical autonomic dysfunction. CONCLUSIONS: The clinical
clues, management strategy, surgical characteristics, vitrectomy outcomes, and
significance of systemic evaluation in vitreous amyloidosis are highlighted. A
novel single mutation (Phe33Ile) in a case of FAP with vitreous amyloidosis from
India is reported.
PMID- 28412069
TI - Whole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of
Retinitis Pigmentosa Accompanied by Pseudocoloboma.
AB - PURPOSE: To identify the genetic cause of and describe the phenotype in 4
families with autosomal recessive retinitis pigmentosa (arRP) that can be
associated with pseudocoloboma. DESIGN: Case series. PARTICIPANTS: Seven patients
from 4 unrelated families with arRP, among whom 3 patients had bilateral early
onset macular pseudocoloboma. METHODS: We performed homozygosity mapping and
whole-exome sequencing in 5 probands and 2 unaffected family members from 4
unrelated families. Subsequently, Sanger sequencing and segregation analysis were
performed in additional family members. We reviewed the medical history of
individuals carrying IDH3A variants and performed additional ophthalmic
examinations, including full-field electroretinography, fundus photography,
fundus autofluorescence imaging, and optical coherence tomography. MAIN OUTCOME
MEASURES: IDH3A variants, age at diagnosis, visual acuity, fundus appearance,
visual field, and full-field electroretinography, fundus autofluorescence, and
optical coherence tomography findings. RESULTS: We identified 7 different
variants in IDH3A in 4 unrelated families, that is, 5 missense, 1 nonsense, and 1
frameshift variant. All participants showed symptoms early in life, ranging from
night blindness to decreased visual acuity, and were diagnosed between the ages
of 1 and 11 years. Four participants with biallelic IDH3A variants displayed a
typical arRP phenotype and 3 participants were diagnosed with arRP and
pseudocoloboma of the macula. CONCLUSIONS: IDH3A variants were identified as a
novel cause of typical arRP in some individuals associated with macular
pseudocoloboma. We observed both phenotypes in 2 siblings carrying the same
compound heterozygous variants, which could be explained by variable disease
expression and warrants caution when making assertions about genotype-phenotype
correlations.
PMID- 28412070
TI - Evaluation of Femtosecond Laser Intrastromal Incision Location Using Optical
Coherence Tomography.
AB - PURPOSE: To use optical coherence tomography (OCT) to evaluate the femtosecond
laser intrastromal incisions made during cataract surgery to reduce corneal
astigmatism. DESIGN: Retrospective case series. PARTICIPANTS: Seventy-seven eyes
of 77 patients. METHODS: Paired intrastromal incisions were created using the
Catalys femtosecond laser (Abbott Medical Optics, Inc., Santa Ana, CA). The
planned intrastromal incision parameters were 20% uncut anterior, 20% uncut
posterior, midpoint depth of 50%, and 90 degrees side cut angle. Optical
coherence tomography scans were obtained 3 weeks or more after surgery to assess
these 4 parameters, and actual values were compared with intended values. MAIN
OUTCOME MEASURES: Percentages of uncut anterior and posterior tissue, midpoint
depth, and degrees of side cut angle. RESULTS: The mean values were 17.2+/-5.8%
(range, 7.2%-36.9%) for uncut anterior, 32.5+/-8.8% (range, 6.0%-57.9%) for uncut
posterior, and 42.3+/-6.6% (range, 25.5%-65.4%) for midpoint depth, which all
were significantly different from the planned parameters (all P < 0.05). The mean
side cut angle was 88.5 degrees +/-5.6 degrees (range, 71 degrees -114 degrees )
and was significantly different from the planned side cut angle of 90 degrees (P
< 0.05). In 50 eyes that had paired intrastromal incisions scanned by the OCT,
there was no correlation between the paired incisions for midpoint depth and side
cut angle (correlation coefficient, r = -0.063 and -0.067, respectively; P >
0.05). CONCLUSIONS: The intrastromal incision midpoint depth was significantly
more anterior than the planned depth of 50%. The locations of paired intrastromal
incisions in each eye were not correlated. Further improvements are needed to
ensure the precise location of the intrastromal incisions made with this device.
PMID- 28412071
TI - Emergency Medicine Myths: Cerebral Edema in Pediatric Diabetic Ketoacidosis and
Intravenous Fluids.
AB - BACKGROUND: Pediatric diabetic ketoacidosis (DKA) is a disease associated with
several complications that can be severe. One complication includes cerebral
edema (CE), and patients may experience significant morbidity with this disease.
OBJECTIVE: This review evaluates the myths concerning CE in pediatric DKA
including mechanism, presentation of edema, clinical assessment of dehydration,
and association with intravenous (i.v.) fluids. DISCUSSION: Multiple
complications may occur in pediatric DKA. CE occurs in < 1% of pediatric DKA
cases, though morbidity and mortality are severe without treatment. Several myths
surround this disease. Subclinical CE is likely present in many patients with
pediatric DKA, though severe disease is rare. A multitude of mechanisms likely
account for development of CE, including vasogenic and cytotoxic causes. Clinical
dehydration is difficult to assess. Literature has evaluated the association of
fluid infusion with the development of CE, but most studies are retrospective,
with no comparator groups. The few studies with comparisons suggest fluid
infusion is not associated with DKA. Rather, the severity of DKA with higher
blood urea nitrogen and greater acidosis contribute to CE. Multiple strategies
for fluid replacement exist. A bolus of 10 mL/kg of i.v. fluid is likely safe,
which can be repeated if hemodynamic status does not improve. CONCLUSIONS:
Pediatric CE in DKA is rare but severe. Multiple mechanisms result in this
disease, and many patients experience subclinical CE. Intravenous fluids are
likely not associated with development of CE, and 10-mL/kg or 20-mL/kg i.v. bolus
is safe.
PMID- 28412072
TI - Do Slow and Steady Residents Win the Race? Modeling the Effects of Peak and
Overall Resident Productivity in the Emergency Department.
AB - BACKGROUND: Emergency medicine residents need to be staffed in a way that
balances operational needs with their educational experience. Key to developing
an optimal schedule is knowing a resident's expected productivity, a poorly
understood metric. OBJECTIVE: We sought to measure how a resident's busiest
(peak) workload affects their overall productivity for the shift. METHODS: We
conducted a retrospective, observational study of resident productivity at an
urban, tertiary care center with a 3-year Accreditation Council for Graduate
Medical Education-approved emergency medicine training program, with 55,000
visits annually. We abstracted resident productivity data from a database of
patient assignments from July 1, 2010 to June 20, 2015, utilizing a generalized
estimation equation method to evaluate physician shifts. Our primary outcome
measure was the total number of patients seen by a resident over a shift. The
secondary outcome was the number of patients seen excluding those in the peak
hour. RESULTS: A total of 14,361 shifts were evaluated. Multivariate analysis
showed that the total number of patients seen was significantly associated with
the number of patients seen during the peak hour, level of training, the timing
of the shift, but most prominently, lower variance in patients seen per hour
(coefficient of variation < 0.10). CONCLUSIONS: A resident's peak productivity
can be a strong predictor of their overall productivity, but the substantial
negative effect of variability favors a steadier pace. This suggests that
resident staffing and patient assignments should generally be oriented toward a
more consistent workload, an effect that should be further investigated with
attending physicians.
PMID- 28412073
TI - Pediatric Acute Flaccid Paralysis: Enterovirus D68-Associated Anterior Myelitis.
AB - BACKGROUND: Enteroviral infections can cause acute flaccid paralysis secondary to
anterior myelitis. Magnetic resonance imaging (MRI) is important in the diagnosis
of this potentially devastating pediatric disease. Before the 2014 outbreak of
Enterovirus D68 (EV-D68), the virus was considered a relatively benign disease.
CASE REPORT: A fully immunized 8-year-old boy was brought to the emergency
department complaining of a cough, headache, neck pain, and right arm pain and
weakness. Deep tendon reflexes in the weak arm could not be elicited. MRI of the
brain and cervical spine revealed anterior myelitis of the cervical spine. The
patient was given intravenous antibiotics, acyclovir, and methylprednisolone with
no initial improvement. He was then given intravenous immunoglobulin over 3 days
with improvement in symptoms. Nasal swab polymerase chain reaction revealed EV
D68. Despite medical management, the child was left with long-term motor
disability in the effected extremity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE
OF THIS?: Acute flaccid paralysis is a potential devastating complication of
enteroviral infections. Extremity complaints in the clinical setting of central
nervous system infection should raise concern for encephalomyelitis. MRI is
extremely helpful in establishing this diagnosis. Prevalence of non-polio
enteroviral paralytic events is increasing in the United States. Potential EV-D68
cases should be reported to local health departments. Emergency medicine
providers should consider this complication in the child with acute, unexplained
significant respiratory illness with new neurologic complaints.
PMID- 28412074
TI - Reversible synthesis of colanic acid and O-antigen polysaccharides in Salmonella
Typhimurium enhances induction of cross-immune responses and provides protection
against heterologous Salmonella challenge.
AB - Colanic Acid (CA) and lipopolysaccharide (LPS) are two major mannose-containing
extracellular polysaccharides of Salmonella. Their presence on the bacterial
surface can mask conserved protective outer membrane proteins (OMPs) from the
host immune system. The mannose moiety in these molecules is derived from GDP
mannose, which is synthesized in several steps. The first two steps require the
action of phosphomannose isomerase, encoded by pmi (manA), followed by
phosphomannomutase, encoded by manB. There are two copies of manB present in the
Salmonella chromosome, one located in the cps gene cluster (cpsG) responsible for
CA synthesis, and the other in the rfb gene cluster (rfbK) involved in LPS O
antigen synthesis. In this study, it was demonstrated that the products of cpsG
and rfbK are isozymes. To evaluate the impact of these genes on O-antigen
synthesis, virulence and immunogenicity, single mutations (Deltapmi, DeltarfbK or
DeltacpsG) and a double mutation (DeltarfbK DeltacpsG) were introduced into both
wild-type Salmonella enterica and an attenuated Deltacya Deltacrp vaccine strain.
The Deltapmi, DeltarfbK and DeltacpsG DeltarfbK mutants were defective in LPS
synthesis and attenuated for virulence. In orally inoculated mice, strain S122
(Deltacrp Deltacya DeltacpsG DeltarfbK) and its parent S738 (Deltacrp Deltacya)
were both avirulent and colonized internal tissues. Strain S122 elicited higher
levels of anti-S. Typhimurium OMP serum IgG than its parent strain. Mice
immunized with S122 were completely protected against challenge with wild-type
virulent S. Typhimurium and partially protected against challenge with either
wild-type virulent S. Choleraesuis or S. Enteritidis. These data indicate that
deletions in rfbK and cpsG are useful mutations for inclusion in future
attenuated Salmonella vaccine strains to induce cross-protective immunity.
PMID- 28412075
TI - Vaccine preferences and acceptance of older adults.
AB - BACKGROUND: Expanding vaccination programs for the older population might be
important as older adults are becoming a larger proportion of the general
population. The aim of this study is to determine the relative importance of
vaccine and disease specific characteristics and acceptance for Dutch older
adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and
influenza vaccination. METHODS: A discrete choice experiment was conducted to
generate choice data that was analyzed using a mixed multinomial logit
statistical model. RESULTS: Important factors that were associated with
vaccination acceptance in older adults are high mortality risk of the infectious
disease, high susceptibility of getting the infectious disease, and high vaccine
effectiveness. Age, influenza vaccination in 2013 and self-perceived health score
were identified as personal factors that affect vaccine preference. Potential
vaccination rates of older adults were estimated at 68.1% for pneumococcal
vaccination, 58.1% for herpes zoster vaccination, 53.9% for pertussis vaccination
and 54.3% for influenza vaccination. For persons aged 50-65, potential
vaccination rates were estimated at 58.1% for pneumococcal vaccination, 49.5% for
herpes zoster vaccination, 43.9% for pertussis vaccination and 42.2% for
influenza vaccination. For persons aged 65 and older, these were respectively
76.2%, 67.5%, 57.5% and 65.5%. DISCUSSION: Our results suggest that older adults
are most likely to accept pneumococcal vaccination of the four vaccines.
Information provision accompanied with the implementation of a new vaccine has to
be tailored for the individual and the vaccine it concerns. Special attention is
needed to ensure high uptake among persons aged 50-65years.
PMID- 28412076
TI - Varicella vaccination elicits a humoral and cellular response in children with
rheumatic diseases using immune suppressive treatment.
AB - OBJECTIVE: To assess humoral and cellular responses to live-attenuated varicella
zoster virus (VZV) vaccination of patients with juvenile idiopathic arthritis
(JIA), juvenile dermatomyositis (JDM) or juvenile scleroderma (JScle) compared to
those of healthy controls (HC). METHODS: Before, 4-6weeks and one year after VZV
vaccination, blood samples of patients and HC were collected. VZV-specific
antibody concentrations were measured by ELISA and multiplex immune-assay. IFN
gamma ELISpot assays were performed to assess VZV-specific T-cell responses.
Cytokine production upon VZV stimulation were measured with a Luminex-assay.
RESULTS: 49 patients (39 JIA, 5 JDM, 5 JScle) and 18 HC were included. All
patients used methotrexate (MTX), 16 also used corticosteroids, 3 patients used
biologics. No disease flares were reported after vaccination. Antibody response
to the vaccine was similar in patients and controls (p=0.139). Use of
immunosuppressive drugs did not affect the response (p=0.203). A second
vaccination (n=21) increased VZV-specific antibody concentrations (p=0.02). VZV
specific T-cells increased after vaccination (p=0.043), with a cytokine profile
suggesting a VZV-specific Th1 and cytotoxic T-cell response. CONCLUSION: The
humoral response to VZV vaccination in patients with pediatric rheumatic diseases
(PRD) is similar to that of HC. Generally, patients are able to mount a VZV
specific cellular response. This study has been registered in the Brazilian
Clinical Trials Registry under number U1111-1189-9837.
PMID- 28412077
TI - Influenza vaccine effectiveness estimates in the Dutch population from 2003 to
2014: The test-negative design case-control study with different control groups.
AB - Information about influenza vaccine effectiveness (IVE) is important for vaccine
strain selection and immunization policy decisions. The test-negative design
(TND) case-control study is commonly used to obtain IVE estimates. However, the
definition of the control patients may influence IVE estimates. We have conducted
a TND study using the Dutch Sentinel Practices of NIVEL Primary Care Database
which includes data from patients who consulted the General Practitioner (GP) for
an episode of acute influenza-like illness (ILI) or acute respiratory infection
(ARI) with known influenza vaccination status. Cases were patients tested
positive for influenza virus. Controls were grouped into those who tested (1)
negative for influenza virus (all influenza negative), (2) negative for influenza
virus, but positive for respiratory syncytial virus, rhinovirus or enterovirus
(non-influenza virus positive), and (3) negative for these four viruses (pan
negative). We estimated the IVE over all epidemic seasons from 2003/2004 through
2013/2014, pooled IVE for influenza vaccine partial/full matched and mismatched
seasons and the individual seasons using generalized linear mixed-effect and
multiple logistic regression models. The overall IVE adjusted for age, GP ILI/ARI
diagnosis, chronic disease and respiratory allergy was 35% (95% CI: 15-48), 64%
(95% CI: 49-75) and 21% (95% CI: -1 to 39) for all influenza negative, non
influenza virus positive and pan-negative controls, respectively. In both the
main and subgroup analyses IVE estimates were the highest using non-influenza
virus positive controls, likely due to limiting inclusion of controls without
laboratory-confirmation of a virus causing the respiratory disease.
PMID- 28412078
TI - A rare tumor of the auricle.
PMID- 28412079
TI - Polymyalgia rheumatica and vagal paraganglioma.
AB - INTRODUCTION: Vagal paraganglioma are rare tumors that are mostly asymptomatic.
We report a case of vagal paraganglioma associated with paraneoplastic
polymyalgia rheumatica and review the literature on benign paragangliomas of the
head and neck associated with paraneoplastic syndrome. CASE REPORT: A 53-year-old
man presented with atypical polymyalgia rheumatica. MRI revealed a tumor that was
then surgically excised. Histological examination confirmed the diagnosis of
benign vagal paraganglioma. Rapid, complete and permanent resolution of all
rheumatological symptoms were observed postoperatively, confirming the diagnosis
of paraneoplastic polymyalgia rheumatica. CONCLUSION: Paraganglioma of the neck
associated with paraneoplastic syndrome remains exceptional. A predisposing gene
mutation must be systematically investigated. Long-term surveillance must be
ensured due to the risk of local recurrence, second tumors or metastasis.
PMID- 28412080
TI - Reproductive parameters of critically endangered European mink (Mustela lutreola)
in captivity.
AB - Founding captive populations is often the last chance for saving endangered
species from extinction. Ensuring successful reproduction is typically most
critical for the maintenance of captive populations, with purposeful selection of
individuals for breeding being one of the crucial aspects. Comparable cross
species data on the determinants of reproduction success are most useful for
solving problems in captive species programs. In the present study, we provide an
overview of a 20-year captive breeding program of the critically endangered
European mink. The mating season starts in March, reaching its peak in the middle
of April. The average gestation length was 43.8days (mode 43), the mean litter
size being 4.4 (mode 4). Litter size and cub survival were negatively correlated
with maternal age but this effect was entirely due to the lower performance of
the females over 4 years of age. Female body weight also showed a positive
correlation with litter size, with the weight itself having increased by 10%
during the 20- year period. We did not find any signs of a cost of reproduction:
the number of litters the female had delivered earlier in her life did not have
an effect on her litter size in the focal year. Beyond the effect of age and
size, individual females did not differ in litter sizes. Consistently, we found
the heritability of litter size to be low. We conclude that, when selecting
females for breeding, there is little need to consider aspects other than genetic
relatedness crucial for avoiding progressive inbreeding.
PMID- 28412082
TI - Corrigendum to "The combination of UCP3-55CT and PPARgamma2Pro12Ala polymorphisms
affects BMI and substrate oxidation in two diabetic populations" [Nutr Metab
Cardiovasc Dis 26 (2016) 400-406].
PMID- 28412081
TI - Nasopharyngeal polymicrobial colonization during health, viral upper respiratory
infection and upper respiratory bacterial infection.
AB - OBJECTIVES: We sought to understand how polymicrobial colonization varies during
health, viral upper respiratory infection (URI) and acute upper respiratory
bacterial infection to understand differences in infection-prone vs. non-prone
patients. METHODS: Nasopharyngeal (NP) samples were collected from 74 acute
otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy
visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus
pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella
catarrhalis (Mcat) were identified by culture. RESULTS: NP colonization rates of
multiple otopathogens during health were significantly lower than during viral
URI, and during URI they were lower than at onset of upper respiratory bacterial
infection in both AOM infection-prone and non-prone children. AOM infection-prone
children had higher polymicrobial colonization rates than non-prone children
during health, viral URI and AOM. Polymicrobial colonization rates of AOM
infection-prone children during health were equivalent to that of non-prone
children during viral URI, and during viral URI were equivalent to that of non
prone during AOM infection. Spn colonization was positively associated with NTHi
and Mcat colonization during health, but negatively during AOM infection.
CONCLUSION: The infection-prone patients more frequently have multiple potential
bacterial pathogens in the NP than the non-prone patients. Polymicrobial
interaction in the NP differs during health and at onset of infection.
PMID- 28412083
TI - Elucidation of the complex metabolic profile of cerebrospinal fluid using an
untargeted biochemical profiling assay.
AB - We sought to determine the molecular composition of human cerebrospinal fluid
(CSF) and identify the biochemical pathways represented in CSF to understand the
potential for untargeted screening of inborn errors of metabolism (IEMs).
Biochemical profiles for each sample were obtained using an integrated
metabolomics workflow comprised of four chromatographic techniques followed by
mass spectrometry. Secondarily, we wanted to compare the biochemical profile of
CSF with those of plasma and urine within the integrated mass spectrometric-based
metabolomic workflow. Three sample types, CSF (N=30), urine (N=40) and EDTA
plasma (N=31), were analyzed from retrospectively collected pediatric cohorts of
equivalent age and gender characteristics. We identified 435 biochemicals in CSF
representing numerous biological and chemical/structural families. Sixty-three
percent (273 of 435) of the biochemicals detected in CSF also were detected in
urine and plasma, another 32% (140 of 435) were detected in either plasma or
urine, and 5% (22 of 435) were detected only in CSF. Analyses of several
metabolites showed agreement between clinically useful assays and the
metabolomics approach. An additional set of CSF and plasma samples collected from
the same patient revealed correlation between several biochemicals detected in
paired samples. Finally, analysis of CSF from a pediatric case with
dihydropteridine reductase (DHPR) deficiency demonstrated the utility of
untargeted global metabolic phenotyping as a broad assessment to screen samples
from patients with undifferentiated phenotypes. The results indicate a single CSF
sample processed with an integrated metabolomics workflow can be used to identify
a large breadth of biochemicals that could be useful for identifying disrupted
metabolic patterns associated with IEMs.
PMID- 28412084
TI - Coding update of the SMFM definition of low risk for cesarean delivery from ICD-9
CM to ICD-10-CM.
AB - In 2015, the Society for Maternal-Fetal Medicine developed a low risk for
cesarean delivery definition based on administrative claims-based diagnosis codes
described by the International Classification of Diseases, Ninth Revision,
Clinical Modification. The Society for Maternal-Fetal Medicine definition is a
clinical enrichment of 2 available measures from the Joint Commission and the
Agency for Healthcare Research and Quality measures. The Society for Maternal
Fetal Medicine measure excludes diagnosis codes that represent clinically
relevant risk factors that are absolute or relative contraindications to vaginal
birth while retaining diagnosis codes such as labor disorders that are
discretionary risk factors for cesarean delivery. The introduction of the
International Statistical Classification of Diseases, 10th Revision, Clinical
Modification in October 2015 expanded the number of available diagnosis codes and
enabled a greater depth and breadth of clinical description. These coding
improvements further enhance the clinical validity of the Society for Maternal
Fetal Medicine definition and its potential utility in tracking progress toward
the goal of safely lowering the US cesarean delivery rate. This report updates
the Society for Maternal-Fetal Medicine definition of low risk for cesarean
delivery using International Statistical Classification of Diseases, 10th
Revision, Clinical Modification coding.
PMID- 28412085
TI - In vivo evidence of significant levator ani muscle stretch on MR images of a live
childbirth.
AB - OBJECTIVE: Vaginal childbirth is believed to be a significant risk factor for the
development of pelvic floor dysfunction later in life. Previous studies have
explored the use of medical imaging and simulations of childbirth to determine
the stretch in the levator ani muscle. A report in 2012 has recorded magnetic
resonance images of a live childbirth of a 24 year old woman giving birth
vaginally for the second time, using a 1.0 Tesla open, high-field scanner. Our
objective was to determine the stretch ratios in the levator muscle using these
magnetic resonance images of live childbirth. STUDY DESIGN: Three-dimensional
magnetic resonance image sequences were obtained to visualize coronal and axial
planes before and after the childbirth. These images were obtained before the
expulsion phase without pushing and were used to reconstruct the levator muscle
and the fetal head in 3 dimensions. The fetal head was approximated to be an
ellipsoid, and it is assumed that its middle section is visible in dynamic
magnetic resonance images. Assuming incompressibility, the full deformation field
of the fetal head is then calculated. Real-time cine magnetic resonance images
were acquired for the during the expulsion phase, occurring over 2 contractions
in the midsagittal plane. The levator muscle stretch is estimated using a custom
program. The program calculates points of contact between the fetal head
ellipsoid and the levator ani muscle model as the head descends down the birth
canal and moves them orthogonal to its surface. Circumferential stretch was
calculated to represent the extension needed to allow the passage of the fetal
head. RESULTS: Starting from a position in the preexpulsion phase, the levator
muscle experiences a maximum circumferential stretch of 248% on the posterior
medial portion of the levator ani muscle, as shown in previously published finite
element simulations. However, the maximal stretch was notably less than that
predicted by finite element models. This is because our baseline 3-dimensional
model of the levator muscle is created from images taken shortly before expulsion
and thus is already in a stretched state. Furthermore, the finite element models
are created from images of a healthy nulliparous woman, while this study uses
images from a para 2 woman. CONCLUSION: This study is the first attempt to
estimate the stretch in levator ani muscle using magnetic resonance images of a
live childbirth. The stretch was significant and the locations corroborate with
previous findings of finite element models.
PMID- 28412086
TI - Tocolysis after preterm premature rupture of membranes and neonatal outcome: a
propensity-score analysis.
AB - BACKGROUND: There are conflicting results regarding tocolysis in cases of preterm
premature rupture of membranes. Delaying delivery may reduce neonatal morbidity
because of prematurity and allow for prenatal corticosteroids and, if necessary,
in utero transfer. However, that may increase the risks of maternofetal infection
and its adverse consequences. OBJECTIVE: The objective of the study was to
investigate whether tocolytic therapy in cases of preterm premature rupture of
membranes is associated with improved neonatal or obstetric outcomes. STUDY
DESIGN: Etude Epidemiologique sur les Petits Ages Gestationnels 2 is a French
national prospective, population-based cohort study of preterm births that
occurred in 546 maternity units in 2011. Inclusion criteria in this analysis were
women with preterm premature rupture of membranes at 24-32 weeks' gestation and
singleton gestations. Outcomes were survival to discharge without severe
morbidity, latency prolonged by >=48 hours and histological chorioamnionitis.
Uterine contractions at admission, individual and obstetric characteristics, and
neonatal outcomes were compared by tocolytic treatment or not. Propensity scores
and inverse probability of treatment weighting for each woman were used to
minimize indication bias in estimating the association of tocolytic therapy with
outcomes. RESULTS: The study population consisted of 803 women; 596 (73.4%)
received tocolysis. Women with and without tocolysis did not differ in neonatal
survival without severe morbidity (86.7% vs 83.9%, P = .39), latency prolonged by
>=48 hours (75.1% vs 77.4%, P = .59), or histological chorioamnionitis (50.0% vs
47.6%, P = .73). After applying propensity scores and assigning inverse
probability of treatment weighting, tocolysis was not associated with improved
survival without severe morbidity as compared with no tocolysis (odds ratio, 1.01
[95% confidence interval, 0.94-1.09], latency prolonged by >=48 hours (1.03 [95%
confidence interval, 0.95-1.11]), or histological chorioamnionitis (1.03 [95%
confidence interval, 0.92-1.17]). There was no association between the initial
tocolytic drug used (oxytocin receptor antagonists or calcium-channel blockers vs
no tocolysis) and the 3 outcomes. Sensitivity analyses of women with preterm
premature rupture of membranes at 26-31 weeks' gestation, women who delivered at
least 12 hours after rupture of membranes, women with direct admission after the
rupture of membranes and the presence or absence of contractions gave similar
results. CONCLUSION: Tocolysis in cases of preterm premature rupture of membranes
is not associated with improved obstetric or neonatal outcomes; its clinical
benefit remains unproven.
PMID- 28412088
TI - Tobacco smoking and its association with cognition in first episode psychosis
patients.
AB - Available evidence suggests that nicotine may enhance cognitive functioning.
Moreover, it has been suggested that the high prevalence of smoking in people
with schizophrenia is in part due to self-medication behaviour to alleviate
cognitive deficits. We assessed the association between tobacco smoking and
cognitive functioning in a large population of first episode psychosis (FEP)
patients (n=304) and healthy controls (n=156). Smokers were not tobacco deprived,
or were minimally deprived (<=2h). Verbal memory, visual memory, working memory,
processing speed, executive function, motor dexterity and attention were
assessed. The smoking prevalence among the FEP group was 57% (n=174). The age at
which patients began smoking cigarettes regularly was 16.2years (SD=3.1), an
average of 12years before experiencing the first frank symptoms of psychosis (age
of onset=28.8; SD=9.3). The number of cigarettes smoked per day was 19.6
(SD=9.4), significantly more than healthy controls [11.0 (SD=7.6); p<0.001].
ANCOVA analysis did not show any significant difference between smokers and non
smokers in in the performance of any of the cognitive tasks in the FEP group or
in the healthy control group, independent of gender, age, education or premorbid
IQ. This suggests chronic exposure to nicotine through cigarette smoking is not
associated with cognitive functioning in first-episode psychosis. These findings
do not support the nicotine self-medication hypothesis as a contributor to the
high prevalence of smoking among individuals suffering from serious mental
illness.
PMID- 28412087
TI - Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine
embryo through cardiac remodeling and fibrosis.
AB - BACKGROUND: Cardiac hypertrophy is highly prevalent in patients with type 2
diabetes mellitus. Experimental evidence has implied that pregnant women with
type 2 diabetes mellitus and their children are at an increased risk of
cardiovascular diseases. Our previous mouse model study revealed that maternal
type 2 diabetes mellitus induces structural heart defects in their offspring.
OBJECTIVE: This study aims to determine whether maternal type 2 diabetes mellitus
induces embryonic heart hypertrophy in a murine model of diabetic embryopathy.
STUDY DESIGN: The type 2 diabetes mellitus embryopathy model was established by
feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks.
Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by
measuring heart size and thickness of the right and left ventricle walls and the
interventricular septum, as well as the expression of beta-myosin heavy chain,
atrial natriuretic peptide, insulin-like growth factor-1, desmin, and
adrenomedullin. Cardiac remodeling was determined by collagen synthesis and
fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining
the expression of connective tissue growth factor, osteopontin, and galectin-3
genes. Cell apoptosis also was measured in the developing heart. RESULTS: The
thicknesses of the left ventricle walls and the interventricular septum of
embryonic hearts exposed to maternal diabetes were significantly thicker than
those in the nondiabetic group. Maternal diabetes significantly increased beta
myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and
desmin expression, but decreased expression of adrenomedullin. Moreover, collagen
synthesis was significantly elevated, whereas fibronectin synthesis was
suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac
remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis
marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type
2 diabetes mellitus activated the proapoptotic c-Jun-N-terminal kinase 1/2 stress
signaling and triggered cell apoptosis by increasing the number of terminal
deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling
positive cells (10.4 +/- 2.2% of the type 2 diabetes mellitus group vs 3.8 +/-
0.7% of the nondiabetic group, P < .05). CONCLUSION: Maternal type 2 diabetes
mellitus induces cardiac hypertrophy in embryonic hearts. Adverse cardiac
remodeling, including elevated collagen synthesis, suppressed fibronectin
synthesis, profibrosis, and apoptosis, is implicated as the etiology of cardiac
hypertrophy.
PMID- 28412089
TI - Inverse association between negative symptoms and body mass index in chronic
schizophrenia.
AB - BACKGROUND: We investigated whether negative symptoms, such as poor motivation or
anhedonia, were associated with higher body mass index (BMI) in stable patients
with schizophrenia chronically treated with antipsychotic medication. METHODS: 62
olanzapine- or clozapine-treated patients with illness duration of at least four
years were selected from an international multicenter study on the
characterization of negative symptoms. All participants completed the Brief
Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale
(PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were
explored, as well as multiple regression analyses. We further explored the
association of two principal component factors of the BNSS and BMI. Subsidiary
analyses re-modeled the above using the negative symptoms subscale of the PANSS
and the EMSLEY factor for negative symptoms for convergent validity. RESULTS:
Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31;
p=0.015). A multiple regression analysis showed that negative symptoms (BNSS
score) and age were significant predictors of BMI (p=0.037). This was mostly
driven by the motivation/pleasure factor of the BNSS. Within this second factor,
BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality
(r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was
positively associated with BNSS (r=0.873, p<0.001), but negatively associated
with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach
significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative
symptoms were associated with higher BMI (assessed using both the BNSS and
EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia
and asociality levels.
PMID- 28412090
TI - Pituitary gland in Bipolar Disorder and Major Depression: Evidence from
structural MRI studies: Special Section on "Translational and Neuroscience
Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This
Section of JAD focuses on the relevance of translational and neuroscience studies
in providing a better understanding of the neural basis of affective disorders.
The main aim is to briefly summarise relevant research findings in clinical
neuroscience with particular regards to specific innovative topics in mood and
anxiety disorders.
AB - BACKGROUND: The function of the hypothalamo-pituitary-adrenal axis (HPA) has been
widely investigated in mood disorders based on its role in regulating stress
response. Particularly, Magnetic Resonance Imaging (MRI) reports have explored
pituitary gland (PG) in both bipolar disorder (BD) and major depressive disorder
(MDD). In this context, the present review summarizes the results from MRI
studies with the final aim of commenting on the presence of common or distinct PG
structural alterations between these two disabling illnesses. METHODS: A
bibliographic search on PUBMED of all MRI studies exploring PG volumes in BD and
MDD as well as first-degree relatives (RELs) from 2000 up to October 2016 was
performed. RESULTS: Following the screening process of the available literature
it can be said that a) PG enlargement has been found in both BD and MDD,
therefore potentially representing a common neurobiological marker characterizing
mood disorders, and b) PG volumes are moderated by age and sex in both illnesses,
although the direction and the extent of this moderation are still not fully
clear. LIMITATIONS: Few MRI studies with heterogeneous results. CONCLUSIONS:
These hypotheses must be taken with caution especially because the heterogeneity
of the results of the studies reviewed does not allow for a definite answer about
the role of PG in affective disorders. Therefore, larger longitudinal studies
investigating PG volumes in BD and MDD patients at the early phases of the
illness, by considering females and males separately, are needed to further
corroborate these findings.
PMID- 28412091
TI - Lansoprazole halts contrast induced nephropathy through activation of Nrf2
pathway in rats.
AB - Contrast-induced nephropathy (CIN) is an important cause of acute kidney injury
characterized by significant mortality and morbidity. To date, there is no
successful protective regimen for CIN especially in poor kidney function
patients. Lansoprazole has been shown to exert antioxidant action through
induction of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. The aim
of the present study is to investigate the potential of lansoprazole to activate
Nrf2 pathway in the kidney and consequently to protect against oxidative stress
induced by iodinated contrast media. Lansoprazole, at a dose of 100 mg/kg, showed
a significant induction of Nrf2 mRNA after 3 h. Administration of contrast media
induced significant increase in serum creatinine and blood urea nitrogen,
histological deterioration, and reduction in total antioxidant capacity.
Moreover, it instigated the defensive Nrf2 gene expression and immunoreactivity.
In addition, there were overexpression of HO-1, caspase 3, p53 and IL6 genes and
downregulation of Bcl2 gene. Pre-treatment with lansoprazole (100 mg/kg)
ameliorated the nephrotoxicity parameters and oxidative stress, improved
histological lesions, and hijacked apoptotic and inflammatory markers that were
provoked by contrast media. In conclusion, lansoprazole attenuates experimental
CIN which might be due to activation of Nrf2 antioxidant defence pathway. These
findings highlight the potential benefit of incorporating lansoprazole in the
protective regimen against CIN especially for susceptible patients.
PMID- 28412092
TI - Chaotic oscillations of gas bubbles under dual-frequency acoustic excitation.
AB - Chaotic oscillation of bubbles in liquids reduces the efficiency of the
sonochemical system and should be suppressed in the practical applications. In
the present paper, a chaos control method based on the dual-frequency approach is
numerically investigated and is proved to be an effective method even for cases
with intensive energy input. It was found that the chaos could be successfully
suppressed by the application of dual-frequency approach in a wide range of
parameter zone (even with high acoustic pressure amplitude). Furthermore,
influences of power allocation between two waves on the chaos control are
quantitatively discussed with clear descriptions of the routes from stable
oscillations to chaos.
PMID- 28412093
TI - Non-Small Cell Lung Cancer as a Second Primary Among Patients With Previous
Malignancy: Who Is at Risk?
AB - BACKGROUND: Patients with previous malignancies could be at increased risk of non
small cell lung cancer (NSCLC). However, the extent of the risk is unknown for
many cancer types; thus, it is unclear who might benefit from screening.
MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results data set
from 1992 to 2012 was used to identify patients with previous malignancies who
received a diagnosis of NSCLC >= 6 months after their initial cancer diagnosis.
Standardized incidence ratios (SIRs) for NSCLC were calculated as a ratio of the
observed to expected cases adjusted by person-years at risk. Cancers with a SIR >
1.0 had a risk of NSCLC greater than expected. The analyses were stratified by
sex, radiation therapy use, and histologic type. RESULTS: Among the cancer
survivors, 32,058 developed NSCLC. Smoking-related (lung, head and neck, bladder)
and hematologic malignancies, regardless of previous radiation therapy, had the
greatest SIR for NSCLC (range, 1.97-4.88). Colorectal and renal cancer survivors
also had an increased SIR for NSCLC (1.16 and 1.21, respectively). Women with
previous pancreatic cancer treated with radiation, breast cancer with or without
radiation therapy, and those with thyroid cancer demonstrated a greater SIR for
lung adenocarcinoma. Men with previous irradiated prostate cancer also had an
elevated SIR (1.08; 99% confidence interval, 1.01-1.15) for lung adenocarcinoma.
Patients with melanoma, prostate or uterine cancer had a lower SIR for NSCLC than
expected. CONCLUSION: Smoking-related malignancies had the greatest risk of
NSCLC. Radiation therapy conferred an elevated risk of NSCLC for certain cancers.
Melanoma, prostate, and uterine cancer survivors had a low risk of NSCLC. These
results could help identify high-risk screening candidates in the growing
population of cancer survivors.
PMID- 28412094
TI - Emotional Problems, Quality of Life, and Symptom Burden in Patients With Lung
Cancer.
AB - OBJECTIVES: Lung cancer is associated with a greater symptom burden than other
cancers, yet little is known about the prevalence of emotional problems and how
emotional problems may be related to the physical symptom burden and quality of
life in newly diagnosed patients with lung cancer. This study aimed to identify
the patient and disease characteristics of patients with lung cancer experiencing
emotional problems and to examine how emotional problems relate to quality of
life and symptom burden. PATIENTS AND METHODS: A total of 2205 newly diagnosed
patients with lung cancer completed questionnaires on emotional problems, quality
of life, and symptom burden. RESULTS: Emotional problems at diagnosis were
associated with younger age, female gender, current cigarette smoking, current
employment, advanced lung cancer disease, surgical or chemotherapy treatment, and
a lower Eastern Cooperative Oncology Group performance score. Additionally,
strong associations were found between greater severity of emotional problems,
lower quality of life, and greater symptom burden. CONCLUSION: Certain
characteristics place patients with lung cancer at greater risk for emotional
problems, which are associated with a reduced quality of life and greater symptom
burden. Assessment of the presence of emotional problems at the time of lung
cancer diagnosis provides the opportunity to offer tailored strategies for
managing negative mood, and for improving the quality of life and symptom burden
management of patients with lung cancer.
PMID- 28412095
TI - The pathology associated with diabetic retinopathy.
AB - This review summarizes the pathological features of diabetic retinopathy. The
lesions occurring in the diabetic retina have been described over many decades
using descriptive and experimental approaches based on clinical studies on
patients, human post-mortem material, animal models and various in vitro systems.
We have also accumulated a wealth of knowledge about basic molecular mechanisms
and key pathogenic processes that drive these abnormalities in diabetic retina.
Despite these advances, there are still limited therapeutic options for diabetic
retinopathy with those currently available only addressing late-stage disease.
With a particular focus on the earlier stages of diabetes, there is growing
appreciation the complex neuronal, glial and microvascular abnormalities which
progressively disrupt retinal function. This is especially true from the
perspective of the neurovascular unit during health and disease. Based on a
strong appreciation of cellular and molecular pathology that underpins diabetic
retinopathy, further advances are anticipated as we drive towards development of
efficacious therapeutic options that can address all stages of disease.
PMID- 28412096
TI - Evolution of saturated hydraulic conductivity with compression and degradation
for municipal solid waste.
AB - Municipal solid waste (MSW) specimens were created from synthetic fresh MSW
degraded in a laboratory scale enhanced degradation reactor. The degree of
degradation and saturated hydraulic conductivity ks were measured to study the
effects of compression and degradation on ks of MSW. The degree of degradation
was characterized through the ratio of cellulose content to lignin content (i.e.,
C/L) and the loss ratio of volatile solid (i.e., DOD). ks of MSW specimens with
different degrees of degradation was measured through triaxial permeameter tests
under different confining pressures. It was found that, when the degradation time
increased from 0month to 18months, ks decreased less than 1 order of magnitude
for specimens with the same porosity (i.e., n=0.63 or 0.69). However, for
specimens with the same degradation time, the decrease of ks could reach 2 orders
of magnitude with n decreasing from 0.8 to 0.6. It indicates that compression has
much greater influence on the reduction of ks than that of degradation. Based on
the Kozeny-Carman model and first-order kinetics, a prediction model related to n
and C/L (or DOD) of MSW was proposed to analyze the evolution of ks with
compression and biodegradation. The methods to determine the values of model
parameters were also proposed.
PMID- 28412097
TI - Optimization and characterization of hydrochar produced from microwave
hydrothermal carbonization of fish waste.
AB - Fish processing results in large amounts of solid and liquid wastes that are
unsustainably dumped into oceans and landfills. Alternative sustainable
technologies that completely utilize seafood wastes are needed. Hydrothermal
carbonization (HTC) that converts moisture-rich biomass into hydrochar is mostly
employed for pure lignocellulosic biowaste. However, the suitability of HTC for
pure non-lignocellulosic waste is unknown. Here, for the first time, a response
surface design guided optimization of microwave hydrothermal carbonization (MHTC)
process parameters, holding temperature (150-210 degrees C) and time (90-120min),
showed that a temperature of approximately 200 degrees C and a time of
approximately 119min yielded maximal hydrochar (~34%). The atomic carbon and ash
content, and calorific value of hydrochar were approximately 25-57%, 20-28%, and
19-24.5MJ/kg respectively, depending on the MHTC operating conditions. Taken
together, these results confirm that MHTC produces hydrochar from fish waste of
quality comparable to one produced from certain lignocellulosic, sewage and
municipal wastes. Therefore, this strategy presents an exciting alternative
technology that can be used either independently or in combination with other
valorization techniques to completely utilize fish wastes irrespective of their
quality.
PMID- 28412098
TI - Supply and demand of some critical metals and present status of their recycling
in WEEE.
AB - New development and technological innovations make electrical and electronic
equipment (EEE) more functional by using an increasing number of metals,
particularly the critical metals (e.g. rare and precious metals) with specialized
properties. As millions of people in emerging economies adopt a modern lifestyle,
the demand for critical metals is soaring. However, the increasing demand causes
the crisis of their supply because of their simple deficiency in the Earth's
crust or geopolitical constraints which might create political issues for their
supply. This paper focuses on the sustainable supply of typical critical metals
(indium, rare earth elements (REEs), lithium, cobalt and precious metals) through
recycling waste electrical and electronic equipment (WEEE). To illuminate this
issue, the production, consumption, expected future demand, current recycling
situation of critical metals, WEEE management and their recycling have been
reviewed. We find that the demand of indium, REEs, lithium and cobalt in EEE will
continuously increasing, while precious metals are decreasing because of new
substitutions with less or even without precious metals. Although the generation
of WEEE in 2014 was about 41.9 million tons (Mt), just about 15% (6.5 Mt) was
treated environmentally. The inefficient collection of WEEE is the main obstacle
to relieving the supply risk of critical metals. Furthermore, due to the
widespread use in low concentrations, such as indium, their recycling is not just
technological problem, but economic feasibility is. Finally, relevant
recommendations are point out to address these issues.
PMID- 28412100
TI - Risk of Acute Kidney Injury after Percutaneous Pharmacomechanical Thrombectomy
Using AngioJet in Venous and Arterial Thrombosis.
AB - BACKGROUND: Percutaneous mechanical thrombectomy is commonly used to treat acute
thrombotic syndromes. AngioJet (AJ) forcibly sprays fibrinolytics to fragment and
aspirate thrombus. It is known to cause hemolysis and gross hematuria, yet
potential consequences to renal function after AJ remain unstudied. We sought to
determine the risk of acute kidney injury (AKI) after AJ when compared with other
lysis techniques. METHODS AND RESULTS: We retrospectively reviewed patients
treated with thrombolysis over 5 years. We identified those treated with AJ or
catheter-directed thrombolysis (CDT). Demographics, indications, procedures, and
laboratory values within 3 days were recorded. AKI was defined as an increase
>25% above the baseline creatinine within 72 hr of the procedure. IN total, 102
patients (52 AJ, 50 CDT) had no statistical difference in mean age (50 and 51),
indication (arterial thrombosis 65% and 88%), or baseline creatinine (0.9 and 1.0
mg/dL), respectively. AKI occurred in 15 (29%) patients treated with AJ versus 4
(8%) of CDT (P = 0.007). Similar numbers of AJ and CDT patients underwent
additional open surgical procedures (21% and 30%, respectively, P = not
significant). Multivariable analysis demonstrated that the odds of AKI were only
increased by AJ (odds ratio [OR] 8.2, 95% confidence interval [CI] 1.98-34.17, P
= 0.004), open surgery (OR 5.4, 95% CI 1.43-20.17, P = 0.013), or a >10% drop in
hematocrit (OR 4.0, 95% CI 1.15-14.25, P = 0.03). CONCLUSIONS: In our
observational study, AJ is an independent risk factor for AKI. Concomitant open
surgery and drop in hematocrit also raise the odds of AKI. Renal injury after AJ
is under-reported in the literature, and may be related to hemolysis from the
device.
PMID- 28412099
TI - Tumor Cell Invadopodia: Invasive Protrusions that Orchestrate Metastasis.
AB - Invadopodia are a subset of invadosomes that are implicated in the integration of
signals from the tumor microenvironment to support tumor cell invasion and
dissemination. Recent progress has begun to define how tumor cells regulate the
plasticity necessary for invadopodia to assemble and function efficiently in the
different microenvironments encountered during dissemination in vivo. Exquisite
mapping by many laboratories of the pathways involved in integrating diverse
invadopodium initiation signals, from growth factors, to extracellular matrix
(ECM) and cell-cell contact in the tumor microenvironment, has led to insight
into the molecular basis of this plasticity. Here, we integrate this new
information to discuss how the invadopodium is an important conductor that
orchestrates tumor cell dissemination during metastasis.
PMID- 28412101
TI - Genetics of recurrent miscarriage and fetal loss.
AB - Despite years of research, miscarriage, particularly when recurrent, continues to
pose a medical challenge. An embryo chromosomal error is responsible for 50-60%
of recurrent cases; however, up to 30-50% remains an enigma. Successful pregnancy
involves different maternal physiologic changes and certain complex interactions
between the fetus and the mother by cytokines, angiogenic mediators and hormones.
To date, research lines have focused on genetic and epigenetic polymorphisms
related mainly to immune response and inflammatory mediators, and have yielded a
significant relationship between recurrent miscarriage and immune mechanisms.
Thus, unknown causes of miscarriage could be due to an immune imbalance induced
by T-helper Th1/Th2/Th17 cytokines and regulatory T cells. Furthermore, these
genes and mediators have long been suspected of being blood markers for the
clinical diagnosis and management of miscarriage; however, more evidence is
required for them to be included in medical practice and obstetric guidelines.
PMID- 28412102
TI - The method of urine sampling is not a valid predictor for vesicoureteral reflux
in children after febrile urinary tract infections.
AB - INTRODUCTION: The likelihood of detecting vesicoureteral reflux (VUR) after
febrile urinary tract infections (UTI) in children logically should correlate
with the correct diagnosis of the UTI. Beneath the unspecific symptoms of fever
urine analysis is the main diagnostic criterion for the exact diagnosis of
febrile UTIs in children. Use of inadequate urine sampling techniques during
diagnosis may lead to impaired accuracy in UTI diagnosis. This could lead to the
assumption that children, having diagnosed their UTI by the use of possibly
inadequate urine sampling techniques should not be evaluated as consequently
compared to those, where the diagnosis relied on sterile urine sampling
techniques. We hypothesized that children with possibly contaminated urine
samples during the initial diagnosis may show a lower rate of VUR in subsequent
VCUGs because of a wrong diagnosis initially compared to children, where accurate
urine sampling techniques were used. PATIENTS: Between 2009 and 2014, a total of
555 patients underwent a primary VCUG at our department indicated because of
febrile UTIs. Patients with urine collection methods other than bag urine and
catheter/suprapubic aspiration (SPA) were excluded from this study (mid-stream
urine, potty urine, n = 149). We evaluated 402 patients (male/female 131/271,
mean age 1.91 years), VUR rates and grades were compared between patients where
urine was sampled by the use of a urine bag only at the time of diagnosis (n =
296, 73.6%) and those where sterile urine sampling (catheter, suprapubic
puncture) was performed (n = 106, 26.3%). 4 patients were excluded due to
equivocal data on urine sampling. RESULTS: VUR rate in children after sterile
urine sampling using a catheter or SPA accounted to 31.1%. In those where urine
samples acquired by the use of urine bags were used, 33.7% showed VUR on
subsequent VCUG (p = 0.718). There were no significant differences as to VUR
grades or gender, although VUR was much more commonly diagnosed in female
patients (37.0% vs 28.2%, p = 0.227) (Figure). CONCLUSION: Children diagnosed
with their UTI by use of bag urine in our experience carried the same risk of
showing a VUR in a subsequent VCUG compared to those, where the initial diagnosis
relied - beneath clinical criteria - on urine samples acquired by suprapubic
puncture or catheterization. Consequently urine-sampling technique during initial
UTI diagnosis alone should not be used as predictor for the reliability of UTI
diagnosis and should not influence the further management after UTI.
PMID- 28412103
TI - Reverse shoulder arthroplasty compared with hemiarthroplasty in the treatment of
acute proximal humeral fractures.
AB - BACKGROUND: Complex proximal humeral fractures may require prosthetic replacement
of the humeral head. Surgical options include reverse shoulder arthroplasty (RSA)
and shoulder hemiarthroplasty; however, the optimal technique remains
controversial. The goal of this study was to compare functional outcomes and
revision rates of RSA with hemiarthroplasty in patients with acute proximal
humeral fractures. MATERIALS AND METHODS: Between January 1, 1999, and December
31, 2014, there were 218 patients who underwent RSA and 427 who underwent
hemiarthroplasty for acute proximal humeral fractures identified through New
Zealand Joint Registry records. Study groups were compared with regard to
baseline characteristics, operative characteristics, and postoperative outcomes
(Oxford Shoulder Score [OSS], revision rate, mortality rate) at 6 months and 5
years after surgery. RESULTS: RSA patients were significantly older (mean age,
78.2 vs. 71.6 years; P < .001), with a higher proportion of female patients (90%
vs. 77%; P < .001) than in the hemiarthroplasty group. No statistically
significant difference existed in revision rate per 100 component-years (0.58
[RSA] vs. 1.16 [hemiarthroplasty]; P = .137) or 1-year mortality (3.8% vs. 3.4%;
P = .805) between both groups. There was no significant difference in 6-month OSS
(29.6 vs. 28.4; P = .305). The RSA group demonstrated a superior mean 5-year OSS
(37.6 vs. 32.7; P = .078); however, the difference did not achieve statistical
significance. CONCLUSIONS: Although our results suggest that RSA patients may
experience superior 5-year functional scores, we have identified no significant
difference in functional outcomes and revision rates between RSA and
hemiarthroplasty in the treatment of acute proximal humeral fractures.
PMID- 28412104
TI - Cement stress predictions after anatomic total shoulder arthroplasty are
correlated with preoperative glenoid bone quality.
AB - HYPOTHESIS: We hypothesized that biomechanical parameters typically associated
with glenoid implant failure after anatomic total shoulder arthroplasty (aTSA)
would be correlated with preoperative glenoid bone quality. METHODS: We developed
an objective automated method to quantify preoperative glenoid bone quality in
different volumes of interest (VOIs): cortical bone, subchondral cortical plate,
subchondral bone after reaming, subchondral trabecular bone, and successive
layers of trabecular bone. Average computed tomography (CT) numbers (in
Hounsfield units [HU]) were measured in each VOI from preoperative CT scans. In
parallel, we built patient-specific finite element models of simulated aTSAs to
predict cement stress, bone-cement interfacial stress, and bone strain around the
glenoid implant. CT measurements and finite element predictions were obtained for
20 patients undergoing aTSA for primary glenohumeral osteoarthritis. We tested
all linear correlations between preoperative patient characteristics (age, sex,
height, weight, glenoid bone quality) and biomechanical predictions (cement
stress, bone-cement interfacial stress, bone strain). RESULTS: Average CT numbers
gradually decreased from cortical (717 HU) to subchondral and trabecular (362 HU)
bone. Peak cement stress (4-10 MPa) was located within the keel hole, above the
keel, or behind the glenoid implant backside. Cement stress, bone-cement
interfacial stress, and bone strain were strongly negatively correlated with
preoperative glenoid bone quality, particularly in VOIs behind the implant
backside (subchondral trabecular bone) but also in deeper trabecular VOIs.
CONCLUSION: Our numerical study suggests that preoperative glenoid bone quality
is an important parameter to consider in aTSA, which may be associated with
aseptic loosening of the glenoid implant. These initial results should now be
confronted with clinical and radiologic outcomes.
PMID- 28412105
TI - How bone quality may influence intraoperative and early postoperative problems
after angular stable open reduction-internal fixation of proximal humeral
fractures.
AB - BACKGROUND: With the introduction of the deltoid tuberosity index (DTI), a simple
radiographic tool has become available to measure bone mineral density of the
proximal humerus. The aim of this study was to assess the influence of local bone
mineral density on the early failure rate after angular stable open reduction
internal fixation of proximal humeral fractures (PHFs). METHODS: We
retrospectively followed up all patients treated with angular stable implants for
PHFs from 2007 to 2014. The fractures were classified according to Neer, and the
DTI, metaphyseal head extension (MHE), medial hinge displacement, and quality of
reduction were assessed. Failures were defined as head screw cutouts. RESULTS:
The study included 146 patients (mean age, 66 years; range, 20-94 years). The
mean follow-up period was 11 months (range, 3-94 months). Of the fractures, 91%
were classified as 2- or 3-part fractures and 9% as 4-part fractures. The mean
DTI was 1.44 (range, 1.19-2.11), and the mean MHE was 12 mm (range, 0-48 mm). The
reduction result was at least acceptable in 80% of fractures. Screw cutouts were
found in 23%. The DTI and MHE were the most significant preoperative predictors
for the reduction result. The DTI (P = .036) and age (P = .02) were independent
preoperative factors, and a good reduction (P = .001) was the only intraoperative
factor influencing cutout. DISCUSSION: This study proves that good bone quality
and a long MHE are helpful for the reduction. Furthermore, good bone quality, a
younger age, and a good reduction prevent later cutout. We conclude that local
bone quality is a relevant factor in the treatment plan for PHFs.
PMID- 28412106
TI - Radial notch labralization for proximal radioulnar joint dysplasia.
AB - BACKGROUND: Chronic posterior subluxation or dislocation of the radial head is
uncommon and difficult to treat. To restore radiocapitellar alignment, procedures
such as deepening of the notch using a high-speed burr have been described, but
they can result in cartilage damage. We hypothesized that a radial notch
labralization using soft tissue could improve radiocapitellar tracking without
violating the joint surface. METHODS: A radial notch labralization was performed
in 3 patients with chronic posterior subluxation of the radial head and
developmental dysplasia of the radial notch in the setting of complex recurrent
instability of the elbow. A soft tissue graft (typically a portion of an
allograft hamstring tendon) was used to create a meniscus-like bumper
posteriorly, thereby deepening the radial notch and reducing its radius of
curvature. A corrective anterior opening wedge ulnar osteotomy was also performed
to realign the radial head with the capitellum. RESULTS: At a mean follow-up of
32 months, all 3 patients were pain free and had maintained a stable joint, with
a functional range of motion. Each patient gave a rating of either "Greatly
Improved" or "Almost Normal" on the Summary Outcome Determination scale.
Radiographs performed during the last follow-up showed improved radiocapitellar
alignment. CONCLUSION: Chronic posterior subluxation or dislocation of the radial
head can occur subsequent to developmental joint changes. The radial notch
labralization using a soft tissue graft associated with a corrective ulnar
osteotomy was successful in restoring radial head stability and avoiding
cartilage damage.
PMID- 28412107
TI - Glenoid morphology in obstetrical brachial plexus lesion: a three-dimensional
computed tomography study.
AB - BACKGROUND: Obstetric brachial plexus lesion (OBPL) frequently leads to
glenohumeral dysplasia, and excessive retroversion of the glenoid is among the
best known developmental disturbances. Most analyses of the glenoid are based on
2-dimensional (D) imaging and do not address glenoid inclination or provide
information on the glenoid in the sagittal plane. We aim to describe the 3-D
deformity of the glenoid in children with OBPL. METHODS: Preoperative computed
tomography (CT) scans of the nonaffected and the affected scapula of 24 children
(aged 5 to 12 years) with developmental disturbances after OBPL years were
analyzed. The dimensions of the scapula and the deformation of the glenoid were
visualized in 3-D. RESULTS: The retroversion of the glenoid fossa was greater in
all affected shoulders, and 2-D measurements significantly overestimated
retroversion compared with angles measured in 3-D. The inclination of the glenoid
fossa was altered, and a distal bony edge loss was observed on 3-D reformations
in the sagittal plane. The reliability of the measured angles was excellent, and
the kappa agreement for the description of the glenoid form was substantial.
Furthermore, the dimensions of the scapula were significantly smaller on the
affected shoulders. CONCLUSION: OBPL is indeed a 3-D disorder. Our measurements
revealed excessive retroversion of the glenoid fossa, and the reliability of the
3-D CT measurements was superior to their 2-D counterparts. 3-D CT reformations
of the glenoid in the coronal and the sagittal plane added further to 3-D
understanding of glenoid morphology in OBPL. These new findings legitimatize a 3
D CT-based description of the glenoid deformities connected with OPBL.
PMID- 28412108
TI - Emergence of the arterial switch procedure for transposition of the great
arteries and the potential cost of surgical innovation.
PMID- 28412110
TI - Change of paradigm or change of heart?
PMID- 28412109
TI - Reengineering valve patients' postdischarge management for adapting to bundled
payment models.
AB - BACKGROUND: Bundled Payments for Care Improvement (BPCI) initiatives were
developed by Medicare in an effort to reduce expenditures while preserving
quality of care. Payment model 2 reimburses based on a target price for 90-day
episode of care postprocedure. The challenge for valve patients is the
historically high (>35%) 90-day readmission rate. We analyzed our institutional
cardiac surgical service line adaptation to this initiative. METHODS: On May 1,
2015, we instituted a readmission reduction initiative (RRI) that included
presurgical risk stratification, comprehensive predischarge planning, and
standardized postdischarge management led by cardiac nurse practitioners (CNPs)
who attempt to guide any postdischarge encounters (PDEs). A prospective database
also was developed, accruing data on all cardiac surgery patients discharged
after RRI initiation. We analyzed detailed PDEs for all valve patients with
complete 30-day follow-up through November 2015. RESULTS: Patients included 219
surgical patients and 126 transcatheter patients. Sixty-four patients had 79
PDEs. Of these 79 PDEs, 46 (58.2%) were guided by CNPs. PDEs were due to fluid
overload/effusion (21, 27%), arrhythmia (17, 22%), bleeding/thromboembolic events
(13, 16%), and falls/somatic complaints (12, 15%). Thirty-day readmission rate
was 10.1% (35/345). Patients with transcatheter aortic valve replacement had a
higher rate of readmission than surgical patients (15.0% vs 6.9%), but were older
with more comorbidities. The median readmission length of stay was 2.0 days
(interquartile range 1.0-5.0 days). Compared with 2014, the 30-day readmission
rate for BPCI decreased from 18% (44/248) to 11% (20/175), P = .05. CONCLUSIONS:
Our reengineering of pre/postdischarge management of BPCI valve patients under
tight CNP control has significantly reduced costly 30-day readmissions in this
high-risk population.
PMID- 28412111
TI - Apneic oxygen insufflation decreases the incidence of hypoxemia during one-lung
ventilation in open and thoracoscopic pulmonary lobectomy: A randomized
controlled trial.
AB - OBJECTIVE: Hypoxemia is common during one-lung ventilation (OLV) for thoracic
surgery. When hypoxemia occurs, surgery is interrupted for rescue ventilation.
Apneic oxygen insufflation (AOI), which provides O2 without applying pressure,
may prevent hypoxemia and does not interrupt surgery. The aim of this study was
to determine the effectiveness of the AOI technique for preventing hypoxemia
during OLV in thoracic surgery. METHODS: Patients undergoing open or
thoracoscopic pulmonary lobectomy from September to December 2015 were included.
Patients were assigned randomly to a non-AOI group or an AOI group (n = 45 each).
OLV was initiated and at the 15-minute mark (OLV15), patients in the AOI group
received oxygen insufflation at 3 L/min to the nonventilated lung for 30 minutes
(OLV45). The primary endpoint was the occurrence of hypoxemia (SaO2 <90%) during
OLV. RESULTS: The demographic and operative data were similar between the 2
groups. The incidence of hypoxemia was greater in the non-AOI than the AOI group
(18% vs 0%; P = .009). DeltaPaO2 (the difference in partial pressure of oxygen in
arterial blood between OLV 45 and 15 minutes) was smaller in the AOI than the non
AOI group (-29 mm Hg vs -69 mm Hg; P = .005). Duration of surgery and incidence
of complications did not vary between groups. CONCLUSIONS: AOI decreases the
incidence of hypoxemia and improves arterial oxygenation during OLV for open and
thoracoscopic surgery. AOI may be a valuable option to prevent hypoxemia. It can
be used before relying on continuous positive airway pressure or intermittent two
lung ventilation and result in fewer interruptions in surgery.
PMID- 28412112
TI - During one-lung ventilation, K.I.S.S.-Keep It Simple Surgeons.
PMID- 28412113
TI - The half-turned truncal switch operation adds a new spin for patients with
complex coronary anatomy and transposition of the great arteries.
PMID- 28412114
TI - Vascular rings: To scope or not to scope.
PMID- 28412115
TI - Outcome of isolated aortic valve replacement in patients with classic and
paradoxical low-flow, low-gradient aortic stenosis.
AB - OBJECTIVE: To analyze operative outcomes and mid-term results after isolated
aortic valve replacement (AVR) in low-flow, low-gradient aortic stenosis (LFLG
AS) by comparing the 2 subcategories (classic low-flow, low-gradient aortic
stenosis [CLFLG] and paradoxical low-flow, low-gradient aortic stenosis [PLFLG]).
METHODS: This was a retrospective analysis of prospectively collected data for
all isolated AVR in LFLG AS performed in our center during the last 13 years (n =
198; CLFLG AS, n = 66, 33% and PLFLG AS, n = 132, 67%). Median follow-up was 3.7
+/- 3.3 years. RESULTS: Preoperative mean gradient was 30.2 +/- 8.8 mm Hg in the
CLFLG AS group and 31.4. +/- 7.0 mmHg in the PLFLG AS group (P = .001). Female
sex, hypertension, and neurologic and renal disease were more frequent in the
PLFLG AS group (P < .01) whereas advanced New York Heart Association class,
atrial fibrillation, and pulmonary hypertension were more frequent in the CLFLG
AS group (P < .01). In-hospital mortality was 3% in the CLFLG AS group and 2.3%
in the PLFLG AS group, P = .08. One- and five-year mortality rates were
significantly greater in the CLFLG AS group (27% and 42% vs 6% and 20% in the
PLFLG AS group, respectively, P = .001). On follow-up, 90% of the total survivors
were in New York Heart Association class I-II, and 51% of the patients in the
CLFLG AS group had an improvement in their ventricular function. CONCLUSIONS: AVR
can be performed in LFLG AS with low in-hospital mortality. CLFLG AS carries
similar in-hospital mortality to PLFLG AS but greater mid-term mortality. Surgery
provided excellent functional status among survivors.
PMID- 28412116
TI - Is new-onset postoperative atrial fibrillation a benign complication?
PMID- 28412117
TI - Bigger is not always better.
PMID- 28412119
TI - I am at my best when I slow down and that is what I will teach my trainees!
PMID- 28412118
TI - Main stem bronchus surgery with pulmonary preservation.
PMID- 28412120
TI - Single lymph node metastasis 10 years after radical resection of a thymoma.
PMID- 28412121
TI - HeartMate 3: Better...but not perfect.
PMID- 28412122
TI - Coronary artery disease is associated with an increased mortality rate following
video-assisted thoracoscopic lobectomy.
AB - OBJECTIVE: To compare the incidence of major adverse cardiac events (MACE) and
mortality following video-assisted thoracoscopic surgery (VATS) lobectomy in
patients with and without coronary artery disease (CAD). METHODS: Multicentre
retrospective analysis of 1699 patients undergoing VATS lobectomy (January 2012
March 2015). CAD definition: previous acute myocardial infarct (AMI), angina,
percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).
MACE definition: postoperative acute myocardial ischemia, cardiac arrest or any
cardiac death. Propensity score analysis was performed to match patients with and
without CAD. Outcomes of the 2 matched groups were compared. RESULTS: The
incidence of MACE and mortality for the entire population was 0.4% (7 patients)
and 1.7% (29 patients); 218 patients (13%) had a history of CAD: 106 previous
AMI, 55 angina, 32 CABG, and 81 PCI. The propensity score yielded 2 well-balanced
groups of 218 pairs with and without CAD. MACE (CAD 2 [0.9%] vs no-CAD 1 [0.5%];
P = 1), cardiovascular and pulmonary complications (CAD 61 [28%] vs no-CAD 51
[23%]; P = .3) and postoperative stay (CAD 7.3 days vs no-CAD 6.2 days; P = .3)
were not different between the groups. The incidence of atrial fibrillation (CAD
31 [14%] vs no-CAD 18 [8.2%]; P = .07), 30-day mortality (CAD: 11 [5%] vs no-CAD
2 [0.9%]; P = .02) and death among complicated patients (CAD 18% vs no-CAD 3.9%;
P = .009) were higher in the CAD group. CONCLUSIONS: The incidence of MACE
following VATS lobectomy in patients with CAD is low and similar to patients
without CAD. However, their risk of postoperative mortality is fivefold higher
compared with non-CAD patients, warranting refined preoperative functional
evaluation and more intense postoperative monitoring.
PMID- 28412123
TI - Discussion.
PMID- 28412124
TI - Time for randomization.
PMID- 28412125
TI - Is gout an easy-to-treat disease? The importance of health determinants.
PMID- 28412126
TI - Gender-specific differences and burn outcome.
PMID- 28412127
TI - Consideration of the use of commercial flights to transfer patients with burns.
PMID- 28412128
TI - The official update of the POSAS: An invitation to share experiences to improve
the POSAS in 'Project POSAS 3.0'.
PMID- 28412129
TI - Acute kidney injury after burn.
AB - Acute kidney injury (AKI) is a common and morbid complication after severe burn,
with an incidence and mortality as high as 30% and 80%, respectively. AKI is a
broad clinical condition with many etiologies, which makes definition and
diagnosis challenging. The most recent Kidney Disease: Improving Global Outcomes
(KDIGO) consensus guidelines defined stage and severity of AKI based on changes
of serum creatinine and urine output (UOP) across time. Burn-related kidney
injury is typically classified as early (0-3days after injury) or late (4-14days
after injury). Early burn AKI is typically due to hypovolemia, poor renal
perfusion, direct cardiac suppression from TNF-alpha, and precipitation of
denatured proteins, while late AKI is often due to sepsis, multi-organ failure,
and nephrotoxic drugs. Diagnosis can be difficult as UOP and biochemical markers
can be relatively normal even with significant renal injury. A sensitive and
specific biomarker for the early diagnosis of AKI is sorely needed, and multiple
potential biomarkers are being investigated. For treatment, the reversal of the
underlying cause is the first intervention. The advent of renal replacement
therapy has significantly improved the mortality of burn patients with AKI and
should be initiated early if injury progresses despite initial maneuvers.
Unfortunately, no beneficial pharmacologic agents have been identified, despite
multiple investigations. Of burn patients who survive AKI, the vast majority do
not receive long-term hemodialysis and they are generally thought to have a good
renal prognosis although this view is shifting. Preliminary data in the burn
population suggest that AKI may confer an increased risk of end-stage renal
disease and long-term all-cause mortality, but further research is needed.
PMID- 28412130
TI - Early excision and grafting (EE&G): Opportunity or threat?
PMID- 28412131
TI - Screening nasal swabs for methicillin resistant Staphylococcus aureus: A regional
burn center's experience.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that
can result in substantial morbidity and mortality. Early detection of MRSA
colonization by screening nasal swabs may be important in the management of burn
injured patients. However, studies examining its use in this population are
limited. The aim of this study was to study the utility of admission MRSA
screening nasal swabs and determine if being positive for MRSA on admission
impacted outcomes. MATERIALS AND METHODS: A retrospective review was conducted of
burn patients who presented to a single regional burn center between June 2012
and December 2014. Electronic medical records and charts were reviewed for
patient demographics and management. MRSA screening swabs were obtained from the
anterior nares of burn patients upon admission. Patients without a MRSA nasal
swab within 48h of admission were excluded. Outcomes analyzed included overall
length of stay, ICU admission and length of stay, mechanical ventilation,
procedure count, time to excision, and wound complications after normalizing to
total body surface area burn size (%TBSA). RESULTS: During the study period, 601
patients received a MRSA screening nasal swab upon admission. Of these, 24
patients screened positive for MRSA (4%). Patients who screened positive for MRSA
had a significantly increased mean length of stay (3.95v 2.36 days; p<0.05) and
number of surgical procedures (1.92v 1.06; p<0.05). Positively screened patients
also had a higher proportion of wound infections (50% v 18.2%; p<0.05), half of
which were caused by MRSA. Subsequent graft complications were seen in 50% of
patients with a wound complication. Only 2 positively screened patients were
started on empiric antibiotics. CONCLUSIONS: Burn patients who screened positive
for MRSA had greater lengths of stay, more surgical procedures, and higher wound
complications. Early identification of MRSA colonized patients in this patient
population might allow for treatment modifications that improve outcomes. Further
study is warranted in a prospective clinical trial.
PMID- 28412132
TI - Pre-existing psychiatric disorder in the burn patient is associated with worse
outcomes.
AB - OBJECTIVE: To compare patient and burn characteristics between patients who had a
pre-existing psychiatric diagnosis and patients who did not in a Burn Unit at an
academic hospital. BACKGROUND: Psychosocial issues are common in patients
recovering from a burn; however, little is known regarding hospital course and
discharge outcomes in patients with a pre-existing psychiatric diagnosis
presenting with a burn. Baseline medical comorbidities of burn patients have been
shown to be a significant risk for in-hospital mortality. METHODS: A
retrospective chart review of 479 consecutive patients admitted to the Burn Unit
of an academic hospital in Halifax, Nova Scotia between March 2nd 1995 and June
1st 2013 was performed. Extensive data regarding patient and burn characteristics
and outcomes was collected. Patients with and without pre-existing psychiatric
diagnoses at the time of hospital admission were compared. RESULTS: Sixty-three
(13%) patients had a psychiatric diagnosis, with the most common being depression
(52%). Forty-percent (n=25/63) of these patients had multiple pre-existing
psychiatric diagnoses. Patients with a psychiatric diagnosis had a greater total
body-surface-area (TBSA)% covered by a third-degree burn (p=0.001), and were more
likely to have an inhalation injury (p<0.001). These patients were also
significantly more likely to experience 6 of the 10 most prevalent in-hospital
complications and had a higher mortality rate (p=0.02). They were less likely to
be discharged home (p=0.001), and more likely to go to a home hospital (p=0.04)
or rehabilitation facility (p=0.03). Psychiatric diagnosis was associated with
significantly more placement issues (e.g. rehab bed unavailability, homeless)
upon discharge from the Burn Unit (p=0.01). The risk of death in burn patients
with pre-existing psychiatric disorders was about three times the risk of death
in patients with no psychiatric disorders when adjusting for other potential
confounders (95% CI, 1.13-9.10; p-value 0.03). CONCLUSION: Presence of a pre
existing psychiatric disorder in the burn patient was associated with worse
outcomes and was a significant predictor of death. Psychiatric diagnoses should
be identified early in burn treatment and efforts should be made to ensure a
comprehensive approach to inpatient support and patient discharge to reduce
unfavorable burn outcomes and placement issues.
PMID- 28412133
TI - The Southwest UK Burns Network (SWUK) experience of electronic cigarette
explosions and review of literature.
AB - INTRODUCTION: Since the introduction of e-cigarettes to the UK market in 2007
their popularity amongst young adults has significantly increased. These lithium
ion powered devices remain unregulated by the Standards Agency and as a result
burns centres across the world have seen an increasing number of patients
presenting with significant burns, resulting from poor quality batteries that
appear to be liable to explode when over-heated, over-charged or incorrectly
stored. METHODS: Retrospective and perspective review of all e-cigarette related
burns presenting to the Southwest Burns Network; South Wales Burns Centre
(Morriston Hospital) or to Bristol burns centre (Southmead Hospital) between Oct
15-July 16, followed by a review of available literature performed and eligible
papers identified using PRISMA 2009 Checklist. RESULTS: South Wales Burns Centre
(Morriston Hospital) (N=5), Bristol burns centre (Southmead Hospital) (N=7). 92%
of injuries were seen in male patients with a mean age of 34.58 (+/-12.7). The
mean TSBA sustained 2.54% of mixed depth, most common anatomical area is the
thigh 83% (n=10) with a mean 23.1(+/-5) days to heal with conservative
management. The literature search yielded 3 case series (Colaianni et al., 2016;
Kumetz et al., 2016; Nicoll et al., 2016) [8,9,12] and 4 case reports (Jablow and
Sexton, 2015; Harrison and Hicklin, 2016; Walsh et al., 2016; Shastry and
Langdorf, 2016) [6,7,10,11]. We compare our findings with the published studies.
CONCLUSION: The import and sale of e-cigarettes remains unrestricted. This
increases the risk of devices being available in the UK market that do not meet
the British Standard Specification, potentially increasing their risk of causing
fire and exploding. Consumers should be made aware of this risk, and advised of
adequate charging and storage procedures. In case lithium ion compounds leak
following a breach in the battery, first aid with mineral oil use is advocated to
avoid a further chemical reaction.
PMID- 28412134
TI - Clinical courses of herpes simplex virus-induced urethritis in men.
AB - We retrieved clinical data of 13 men having herpes simplex virus (HSV)-induced
non-gonococcal urethritis (NGU) without visible herpetic lesions. They visited a
clinic in Sendai, Japan, between April 2013 and December 2015. All the men
complained of dysuria. Meatitis was observed in 9 of the 13 men. Mononuclear
cells were observed in the urethral smears from 9 men. The 13 men were treated
with azithromycin or sitafloxacin regimen. First-voided urine (FVU) specimens
became negative for HSV in 8 of the 10 men who returned to the clinic after
antibacterial treatment, and urethritis symptoms were alleviated. However,
herpetic lesions were observed at the follow-up visits in 3 men, and 2 of them
were still positive for HSV in their FVU. HSV could be a cause of acute
urethritis without causing visible herpetic lesions. The shedding of HSV from the
urethra would spontaneously cease with alleviation of urethritis symptoms in most
cases of HSV-induced NGU without antiviral therapy. However, new herpetic lesions
could be developed in some cases. Early antiviral therapy is beneficial for
patients with HSV infections. The development of meatitis and the mononuclear
cell response in the urethral smear could be helpful to diagnose HSV-induced NGU.
Therefore, we should presumptively initiate anti-HSV therapy for patients with
signs and symptoms suggestive of HSV-induced NGU at their first presentation.
PMID- 28412135
TI - Moving beyond quality control in diagnostic radiology and the role of the
clinically qualified medical physicist.
AB - Quality control (QC), according to ISO definitions, represents the most basic
level of quality. It is considered to be the snapshot of the performance or the
characteristics of a product or service, in order to verify that it complies with
the requirements. Although it is usually believed that "the role of medical
physicists in Diagnostic Radiology is QC", this, not only limits the contribution
of medical physicists, but is also no longer adequate to meet the needs of
Diagnostic Radiology in terms of Quality. In order to assure quality practices
more organized activities and efforts are required in the modern era of
diagnostic radiology. The complete system of QC is just one element of a
comprehensive quality assurance (QA) program that aims at ensuring that the
requirements of quality of a product or service will consistently be fulfilled. A
comprehensive Quality system, starts even before the procurement of any
equipment, as the need analysis and the development of specifications are
important components under the QA framework. Further expanding this framework of
QA, a comprehensive Quality Management System can provide additional benefits to
a Diagnostic Radiology service. Harmonized policies and procedures and elements
such as mission statement or job descriptions can provide clarity and consistency
in the services provided, enhancing the outcome and representing a solid platform
for quality improvement. The International Atomic Energy Agency (IAEA) promotes
this comprehensive quality approach in diagnostic imaging and especially supports
the field of comprehensive clinical audits as a tool for quality improvement.
PMID- 28412136
TI - Dose painting by means of Monte Carlo treatment planning at the voxel level.
AB - PURPOSE: To develop a new optimization algorithm to carry out true dose painting
by numbers (DPBN) planning based on full Monte Carlo (MC) calculation. METHODS:
Four configurations with different clustering of the voxel values from PET data
were proposed. An optimization method at the voxel level under Lineal Programming
(LP) formulation was used for an inverse planning and implemented in CARMEN, an
in-house Monte Carlo treatment planning system. RESULTS: Beamlet solutions
fulfilled the objectives and did not show significant differences between the
different configurations. More differences were observed between the segment
solutions. The plan for the dose prescription map without clustering was the
better solution. CONCLUSIONS: LP optimization at voxel level without dose-volume
restrictions can carry out true DPBN planning with the MC accuracy.
PMID- 28412137
TI - Are Markers of Systemic Inflammation Good Prognostic Indicators in Colorectal
Cancer?
AB - Systemic inflammation has been proved to play a crucial role in promoting cancer
progression and metastasis in many cancer types, including colorectal cancer
(CRC). The aim of the present review was to provide an overview of studies
regarding the prognostic value of inflammation-based markers in patients with
CRC. A literature search was performed for articles reporting the prognostic
value of the Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-to
lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to
monocyte ratio (LMR) in relation to CRC outcomes. In resectable early-stage CRC,
high GPS scores seem significantly associated with cancer-specific survival. It
has also been suggested that adjuvant chemotherapy for stage II CRC could improve
cancer-specific survival in patients with high GPS scores. In patients with both
resectable and unresectable metastatic CRC and a higher GPS score, all studies
suggested poorer overall survival. In early-stage and resectable metastatic CRC,
the NLR seemed related to overall survival; however, the data for disease-free
survival were discordant. In metastatic disease, a possible correlation between a
greater NLR and poorer response to bevacizumab has been suggested. Data
concerning the prognostic and predictive role of the PLR and LMR in CRC are to
date insufficient. In patients with unresectable metastatic disease, inflammation
markers can be used to predict the chemotherapeutic outcome and monitor tumor
progression. However, further prospective studies might lead to better risk
stratification for patients eligible for curative surgery, thus, allowing the
restriction of neoadjuvant and adjuvant therapy to patients with high-risk CRC.
PMID- 28412138
TI - Early Postoperative FDG-PET-CT Imaging Results in a Relevant Upstaging in the pN2
Subgroup of Stage III Colorectal Cancer Patients.
AB - INTRODUCTION: Clinical practice guidelines regarding follow-up in patients after
curative resection of colorectal cancer (CRC) vary widely. Current follow-up
recommendations do not include additional postoperative imaging before starting
adjuvant treatment in any patients. We evaluated the potential benefit of our
institutional approach, recommending 18fluor-deoxy-glucose (FDG)-positron
emission tomography (PET)-computed tomography (CT) imaging in CRC stage III
patients with >=4 locoregional lymph node metastases (pN2). PATIENTS AND METHODS:
Our study included all patients from a single center with complete resection of a
pT1-4, pN2, cM0 CRC. All patients were considered free of distant metastases on
the basis of preoperative CT imaging of the chest, abdomen, and pelvis. The main
objective of the present study was to assess the proportion of patients with
changes of therapeutic management (defined as any other treatment than the
preplanned adjuvant chemotherapy) because of the results of additional
postoperative FDG-PET-CT imaging. RESULTS: Fifty patients (22 female/28 male)
were included; the median age was 64 years (range, 37-78 years). Previously
undiagnosed metastatic disease resulting in a change of the therapeutic
management was detected using postoperative FDG-PET-CT imaging in 7 patients
(14.0%; 95% confidence interval, 5.8%-26.7%). The number needed to screen to
detect new or previously occult metastases was 7 (7 of 50). CONCLUSION: To our
knowledge, this is the first study to evaluate the role of an additional
postoperative FDG-PET-CT scan before adjuvant treatment in patients with
completely resected CRC with >=4 lymph node metastases (pT1-4, pN2) and without
distant metastases on preoperative CT imaging (cM0). Postoperative FDG-PET-CT
imaging represents a valuable tool for the detection of new macrometastases in
the subgroup of pN2 cM0 CRC patients. The low number needed to screen for
consequent therapeutic changes is clinically relevant and should be further
evaluated.
PMID- 28412139
TI - Comparative Effectiveness Research: The Impact of Biologic Agents in Ethnic
Minorities With Metastatic Colorectal Cancer.
AB - BACKGROUND: Biologic agents have improved the outcomes of patients with
metastatic colorectal cancer (mCRC). However, the clinical trials included a
predominately white population (85%), with Hispanic and black patients
underrepresented. Thus, the real world benefit for the latter remains unknown.
Comparative effectiveness research is a tool allowing for this exploration.
PATIENTS AND METHODS: The demographic and clinical characteristics of patients
treated for mCRC from 2000 to 2011 were extracted from the medical records of
Montefiore Medical Center. A semiparametric accelerated failure time model was
used to assess the survival differences between patients receiving chemotherapy
(CT) alone versus CT plus biologic agents (CBT). RESULTS: Of the 290 patients
(black, 45.9%; Hispanic, 26.2%; and white, 27.9%), 53.8% received biologic
agents. The median overall survival was 15.2 months in the CT-alone group and
25.6 months in CBT group (P = .004). On univariate analysis, a lower number of
metastatic sites, carcinoembryonic antigen < 41 ng/mL, and more lines of CT were
associated with improved overall survival. In a propensity score-based analysis
of the entire cohort, CBT offered a survival benefit compared with CT alone
(increased median survival, 1.44-fold; 95% confidence interval [CI], 1.11-1.86; P
= .038). The results of the subgroup analysis suggested a survival benefit for
white patients (2.01; 95% CI, 1.26-3.23; P = .031) but not for Hispanic (1.42;
95% CI, 0.91-2.20; P = .370) or black (1.12; 95% CI, 0.76-1.66; P = .596)
patients. CONCLUSION: In the present cohort, CBT was associated with longer
survival, with the effect mainly driven by the outcomes for white patients, with
black patients not appearing to benefit. These data are provocative and warrant
further confirmation. Efforts to increase ethnic minority patients' enrollment in
clinical trials is required to prospectively define the benefit from novel
therapies.
PMID- 28412140
TI - Chronic sleep restriction promotes brain inflammation and synapse loss, and
potentiates memory impairment induced by amyloid-beta oligomers in mice.
AB - It is increasingly recognized that sleep disturbances and Alzheimer's disease
(AD) share a bidirectional relationship. AD patients exhibit sleep problems and
alterations in the regulation of circadian rhythms; conversely, poor quality of
sleep increases the risk of development of AD. The aim of the current study was
to determine whether chronic sleep restriction potentiates the brain impact of
amyloid-beta oligomers (AbetaOs), toxins that build up in AD brains and are
thought to underlie synapse damage and memory impairment. We further investigated
whether alterations in levels of pro-inflammatory mediators could play a role in
memory impairment in sleep-restricted mice. We found that a single
intracerebroventricular (i.c.v.) infusion of AbetaOs disturbed sleep pattern in
mice. Conversely, chronically sleep-restricted mice exhibited higher brain
expression of pro-inflammatory mediators, reductions in levels of pre- and post
synaptic marker proteins, and exhibited increased susceptibility to the impact of
i.c.v. infusion of a sub-toxic dose of AbetaOs (1pmol) on performance in the
novel object recognition memory task. Sleep-restricted mice further exhibited an
increase in brain TNF-alpha levels in response to AbetaOs. Interestingly, memory
impairment in sleep-restricted AbetaO-infused mice was prevented by treatment
with the TNF-alpha neutralizing monoclonal antibody, infliximab. Results
substantiate the notion of a dual relationship between sleep and AD, whereby
AbetaOs disrupt sleep/wake patterns and chronic sleep restriction increases brain
vulnerability to AbetaOs, and point to a key role of brain inflammation in
increased susceptibility to AbetaOs in sleep-restricted mice.
PMID- 28412141
TI - Toll like receptor 4 activation can be either detrimental or beneficial following
mild repetitive traumatic brain injury depending on timing of activation.
AB - A history of repeated concussion has been linked to the later development of
neurodegeneration, which is associated with the accumulation of
hyperphosphorylated tau and the development of behavioral deficits. However, the
role that exogenous factors, such as immune activation, may play in the
development of neurodegeneration following repeated mild traumatic brain injury
(rmTBI) has not yet been explored. To investigate, male Sprague-Dawley rats were
administered three mTBIs 5days apart using the diffuse impact-acceleration model
to generate ~100G. Sham animals underwent surgery only. At 1 or 5days following
the last injury rats were given the TLR4 agonist, lipopolysaccharide (LPS,
0.1mg/kg), or saline. TLR4 activation had differential effects following rmTBI
depending on the timing of activation. When given at 1day post-injury, LPS
acutely activated microglia, but decreased production of pro-inflammatory
cytokines like IL-6. This was associated with a reduction in neuronal injury,
both acutely, with a restoration of levels of myelin basic protein (MBP), and
chronically, preventing a loss of both MBP and PSD-95. Furthermore, these animals
did not develop behavioral deficits with no changes in locomotion, anxiety,
depressive-like behavior or cognition at 3months post-injury. Conversely, when
LPS was given at 5days post-injury, it was associated acutely with an increase in
pro-inflammatory cytokine production, with an exacerbation of neuronal damage and
increased levels of aggregated and phosphorylated tau. At 3months post-injury,
there was a slight exacerbation of functional deficits, particularly in cognition
and depressive-like behavior. This highlights the complexity of the immune
response following rmTBI and the need to understand how a history of rmTBI
interacts with environmental factors to influence the potential to develop later
neurodegeneration.
PMID- 28412142
TI - Early enriched physical environment reverses impairments of the hippocampus, but
not medial prefrontal cortex, of socially-isolated mice.
AB - Early social isolation (SI) produces a variety of emotional, behavioral and
cognitive abnormalities. Conversely, environmental enrichment (EE), a complicated
social and physical construct, offers beneficial effects on brain plasticity and
development. However, whether or not exclusive physical EE is sufficient to
reverse the adverse consequences of early SI remains unclear. Here we reported
that 1month-old solitary mice housed in the EE for 8weeks corrected spatial
cognitive dysfunction, but did not ameliorate social interaction deficits and
increased anxiety-like behavior. Pathological analyses revealed that the enriched
environment decreased cellular apoptosis, synaptic protein loss, myelination
defect and microglial activation in the hippocampus, but not medial prefrontal
cortex (mPFC) of mice housed singly. Moreover, increased nuclear factor-kappaB
and interleukin-1beta levels, and downregulation of brain-derived neurotrophic
factor signaling pathway were normalized in the hippocampus rather than mPFC of
these animals. Our results revealed a brain region-specific effectiveness of
physical EE in remediating brain impairment of adolescent SI mice, with a
complete reversal of hippocampus-dependent cognitive dysfunctions, but without
mitigation of mPFC associated anxiety and social interaction defects. This
finding emphasizes the irreplaceable role of social life for the early brain
development.
PMID- 28412143
TI - Thermo-sensitive assembly of the biomaterial REP reduces hematoma volume
following collagenase-induced intracerebral hemorrhage in rats.
AB - Intracerebral hemorrhage (ICH) frequently results in severe disabilities and high
mortality. RGD-containing elastin-like polypeptide (REP), a modified elastin-like
polypeptide (ELP), is a thermally responsive biopolymer. REP has high affinity
for cells and is known to show non-immunotoxicity, -cytotoxicity, and
inflammatory responses. Here we found that administration of REP in the acute
phase of the ICH rat model reduced the hematoma volume, decreased the number of
activated microglia, attenuated the expression of von Willebrand Factor (vWF),
and prevented the leakage of immunoglobulin G (IgG) into the cerebral parenchyma
without any occlusion of intact microvessels. Therefore, the present data suggest
that REP treatment could be a novel therapeutic strategy for attenuating the
acute phase of ICH.
PMID- 28412144
TI - Quantitative microscopy-based measurements of circulating nanoparticle
concentration using microliter blood volumes.
AB - Nanoparticles (NPs) are potential drug delivery vehicles for treatment of a broad
range of diseases. Intravenous (IV) administration, the most common form of
delivery, is relatively non-invasive and provides (in theory) access throughout
the circulatory system. However, in practice, many IV injected NPs are quickly
eliminated by specialized phagocytes in the liver and spleen. Consequently, new
materials have been developed with the capacity to significantly extend the
circulating half-life of IV administered NPs. Unfortunately, current procedures
for measuring circulation half-lives are often expensive, time consuming, and can
require large blood volumes that are not compatible with mouse models of disease.
Here we describe a simple and reliable procedure for measuring circulation half
life utilizing quantitative microscopy. This method requires only 2MUL of blood
and minimal sample preparation, yet provides robust quantitative results.
PMID- 28412145
TI - Role of flexible bronchoscopy in non-resolving community-acquired pneumonia - A
retrospective analysis.
PMID- 28412146
TI - Acetate-detoxification of wood hydrolysates with alkali tolerant Bacillus sp. as
a strategy to enhance the lipid production from Rhodosporidium toruloides.
AB - The aim of the current work was to convert an acetate-rich hemicellulose liquid
fraction (LF) from hot-water extraction of Betula pendula to oils for biodiesel,
with Rhodosporidium toruloides. The toxicity of acetate was circumvented by
biological detoxification with an isolated alkali-tolerant and acetate-resistant
Bacillus sp. strain. Removal of other lignocellulose-derived inhibitors, such as
furfural and phenols, was evaluated by two strategies; an activated carbon (AC)
treatment of the undiluted LF, and dilution of the LF by 25% (0.75LF) and 50%.
(0.50LF). The bacterium consumed most of the acetic acid in 6-8days in the
treated or diluted media, which were subsequently used for cultivation of the
yeast, for conversion of sugars to oils. The oil concentration reached 2.8 and
1.8g/L, in the AC LF and 0.75LF medium, respectively. In comparison, the oil
accumulation in the same media without prior cultivation of Bacillus sp. was 0.86
and 0.03g/L, respectively.
PMID- 28412147
TI - Anaerobic co-digestion of microalgal biomass and wheat straw with and without
thermo-alkaline pretreatment.
AB - This study aimed at analyzing the anaerobic co-digestion of microalgal biomass
grown in wastewater and wheat straw. To this end, Biochemical Methane Potential
(BMP) tests were carried out testing different substrate proportions (20-80, 50
50 and 80-20%, on a volatile solid basis). In order to improve their
biodegradability, the co-digestion of both substrates was also evaluated after
applying a thermo-alkaline pretreatment (10% CaO at 75 degrees C for 24h). The
highest synergies in degradation rates were observed by adding at least 50% of
wheat straw. Therefore, the co-digestion of 50% microalgae - 50% wheat straw was
investigated in mesophilic lab-scale reactors. The results showed that the
methane yield was increased by 77% with the co-digestion as compared to
microalgae mono-digestion, while the pretreatment only increased the methane
yield by 15% compared to the untreated mixture. Thus, the anaerobic co-digestion
of microalgae and wheat straw was successful even without applying a thermo
alkaline pretreatment.
PMID- 28412148
TI - No evidence to support a role for Helicobacter pylori infection and plasminogen
binding protein in autoimmune pancreatitis and IgG4-related disease in a UK
cohort.
AB - BACKGROUND AND OBJECTIVES: Helicobacter pylori (H.pylori) plasminogen binding
protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis
(AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We
investigated exposure to H. pylori infection, cytokine response and immunological
memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. METHODS:
Clinical and endoscopic evidence of peptic ulceration, serological H. pylori
exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52
disease controls (DC) with autoimmune or inflammatory conditions with an elevated
serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and
immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were
used to detect immune responses to H. pylori PBP. RESULTS: 85% of IgG4-RD
patients had pancreatic and/or biliary disease, 89% had extra-pancreatic
manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%),
gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in
IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic
inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1
4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54)
compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B
cell memory to H. pylori PBP did not differ between IgG4-RD and DC. CONCLUSIONS:
In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H.
pylori, cytokine response and immunological memory to H. pylori PBP did not
differ in IgG4-RD patients compared with DC. This study does not support a role
for H. pylori PBP as a microbial antigen in IgG4-RD. KEYWORDS FOR ABSTRACT:
Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.
PMID- 28412149
TI - Prevalence of arrhythmias in patients with type 2 diabetes and the role of
structural changes in myocardium in their development.
AB - OBJECTIVE: The aim of the study was to evaluate the prevalence of arrhythmias in
patients with type 2 diabetes and their relationships with the structural
parameters of the heart. METHODS: A retrospective case-control study was
conducted using clinical and biochemical profiles of patients with diabetes at
the Endocrinology Centre and City Clinical Hospital No. 40, Ekaterinburg, Russia.
RESULTS: The total study sample included 75 subjects. The average age (SD) was
48.2 (5.6) years, and the mean duration of diabetes (SD) was 6.2 (2.4) years. The
most common type of extrasystoles were the single supraventricular extrasystoles,
observed in 72.29% of cases (vs 38.89% in the control group) and paired
supraventricular extrasystoles, which were identified in 30% of cases (vs 19.44%
in the control group). Ventricular cardiac arrhythmias in the form of ventricular
extrasystoles (VE) were identified in 25.71% of cases (13.89% in the control
group). CONCLUSIONS: This study revealed the signs of the morphological
restructuring of the right chambers of the heart and a relatively high prevalence
of supraventricular arrhythmias in the early stages of type 2 diabetes. Moreover,
according to the results, the incidence of some types of supraventricular
arrhythmias and the occurrence of tachycardia episodes in patients with type 2
diabetes mostly depends on the restructuring of the right chambers of the heart,
which may be caused by the peculiarities of the cardiac innervation, with the
higher density of choline and adrenergic plexuses in the right chambers.
PMID- 28412150
TI - Epidemiological features of and changes in incidence of infectious diseases in
China in the first decade after the SARS outbreak: an observational trend study.
AB - BACKGROUND: The model of infectious disease prevention and control changed
significantly in China after the outbreak in 2003 of severe acute respiratory
syndrome (SARS), but trends and epidemiological features of infectious diseases
are rarely studied. In this study, we aimed to assess specific incidence and
mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China
and to investigate the overall effectiveness of current prevention and control
strategies. METHODS: Incidence and mortality data for 45 notifiable infectious
diseases were extracted from a WChinese public health science data centre from
2004 to 2013, which covers 31 provinces in mainland China. We estimated the
annual percentage change in incidence of each infectious disease using joinpoint
regression. FINDINGS: Between January, 2004, and December, 2013, 54 984 661 cases
of 45 infectious diseases were reported (average yearly incidence 417.98 per 100
000). The infectious diseases with the highest yearly incidence were hand, foot,
and mouth disease (114.48 per 100 000), hepatitis B (81.57 per 100 000), and
tuberculosis (80.33 per 100 000). 132 681 deaths were reported among the 54 984
661 cases (average yearly mortality 1.01 deaths per 100 000; average case
fatality 2.4 per 1000). Overall yearly incidence of infectious disease was higher
among males than females and was highest among children younger than 10 years.
Overall yearly mortality was higher among males than females older than 20 years
and highest among individuals older than 80 years. Average yearly incidence rose
from 300.54 per 100 000 in 2004 to 483.63 per 100 000 in 2013 (annual percentage
change 5.9%); hydatid disease (echinococcosis), hepatitis C, and syphilis showed
the fastest growth. The overall increasing trend changed after 2009, and the
annual percentage change in incidence of infectious disease in 2009-13 (2.3%) was
significantly lower than in 2004-08 (6.2%). INTERPRETATION: Although the overall
incidence of infectious diseases was increasing from 2004, the rate levelled off
after 2009. Effective prevention and control strategies are needed for diseases
with the highest incidence-including hand, foot, and mouth disease, hepatitis B,
and tuberculosis-and those with the fastest rates of increase (including hydatid
disease, hepatitis C, and syphilis). FUNDING: Chinese Ministry of Science and
Technology, National Natural Science Foundation (China).
PMID- 28412151
TI - Infectious diseases in China in the post-SARS era.
PMID- 28412152
TI - Discrepancies between home medication and patient documentation in primary care.
AB - BACKGROUND: Medication Reconciliation leads to quick detection of drug-related
problems, studies in ambulatory care are scarce. The recently introduced
Medication Plan in Germany serves as an ideal basis for Medication
Reconciliation. OBJECTIVE: The study aim was to provide accurate data on the
magnitude of discrepancy between the prescription and the actually taken
medicine. Clinical relevance of discrepancies was assessed to estimate the impact
on medication safety. METHODS: Patients were assessed at home, data was
reconciled with the physician's documentation. Discrepancies were analyzed and
stratified. Risk for hospitalization, risk for falls and the potential for drug
drug interactions was estimated based on literature. Drugs were tested for its
origin and grouped to indication clusters. Detected DRPs at a Medication Review
were linked to the results at Medication Reconciliation. RESULTS: Medication of
142 elderly patients from 12 practices was reconciled. 1498 drugs were found at
the home assessment, 1099 (73.4%) of which were detected in the physician's
documentation. 94.4% of the patients were affected by discrepancies. A total of
2.8 +/- 2.4 drugs was undocumented per patient. 26.6% of missing drugs were
prescribed by medical specialists, 42.5% of drugs of unknown origin were
prescription drugs. 53.9% of the patients used a undocumented drug, which carried
a high risk for hospitalization. 23.1% of the drugs not covered were used for
treatment of cardiovascular diseases. 65.8% of the differing drugs caused at
least one DRP. CONCLUSION: A high discrepancy between the drugs used by the
patient and the medication documented by the primary care physician could be
found. Relating drugs had a profound systemic effect and were particular relevant
to medication safety. Many drugs were prescription drugs. The majority of
differing drugs caused DRPs. A collaborative Medication Reconciliation as part of
a Medication Management could compile the entire medication and increase patient
safety.
PMID- 28412153
TI - The effect of counseling on willingness to use a hypothetical medication and
perceptions of medication safety.
AB - BACKGROUND: Poor medication adherence is an ongoing issue, and contributes to
increased hospitalizations and healthcare costs. Although most adverse effects
are rare, the perceived risk of adverse effects may contribute to low adherence
rates. OBJECTIVES: The objective of this study was to determine how adverse
effect likelihood and pharmacist counseling on adverse effect prevention affects
individuals': (1) willingness to use a hypothetical medication and (2)
perceptions of medication safety. METHODS: This study used a 3 * 3 experimental
design. Participants (n = 601) viewed a hypothetical scenario asking them to
imagine being prescribed an anti-asthma medication that could cause fungal
infections of the throat. Participants were randomized to 1 of 9 scenarios that
differed on: probability of developing an infection (5%, 20%, no probability
mentioned) and whether they were told how to reduce the risk of infection (no
prevention strategy discussed, prevention strategy discussed, prevention strategy
discussed with explanation for how it works). Participants were recruited through
Amazon Mechanical Turk. RESULTS: Participants were less willing to take the
medication (F = 12.86, p < 0.0001) and considered it less safe (F = 13.11, p <
0.0001) when the probability of fungal infection was presented as 20% compared to
5% or when no probability information was given. Participants were more willing
to take the medication (F = 11.78, p < 0.0001) and considered it safer (F =
11.17, p < 0.0001) when a prevention strategy was given. Finally, there was a non
statistically significant interaction between the probability and prevention
strategy information such that provision of prevention information reduced the
effect of variation in the probability of infection on both willingness to use
the medication and perceived medication safety. CONCLUSIONS: Optimal risk
communication involves more than informing patients about possible adverse
effects. Pharmacists could potentially improve patient acceptance of therapeutic
recommendations, and allay medication safety concerns, by counseling about
strategies patients can implement to reduce the perceived risk of adverse
effects.
PMID- 28412154
TI - Quality Indicator for Epilepsy Treatment 15 (QUIET-15): Intervening after
recurrent seizures in the elderly.
AB - In this study, we examined the provision of care to older adults with epilepsy
and compliance with the "Quality Indicator for Epilepsy Treatment 15" (QUIET-15)
measure. We analyzed 2008-2010, 5% random sample of Medicare beneficiaries
augmented with data from all beneficiaries who identified as a minority with
claims related to seizures (780.3x) or epilepsy (345.xx). Of 36,912 identified
epilepsy cases, 12.6% had >=1 emergency room (ER) visit for seizure(s). For those
who presented to ER, among those taking anti-epileptic drugs (AEDs), AED was
changed in 15.4%, dose adjusted in 19.7%, and stopped in 14.9%; among those not
taking AED, therapy was initiated in 68.5%. In adjusted logistic regressions,
African-Americans were more likely to have recurrent seizures than Whites (OR
1.41, 95%CI 1.27-1.56), while Asians were less likely to have recurrent seizures
(OR 0.71, 95%CI 0.57-0.89). There were no significant racial/ethnic differences
in the likelihood of a post-seizure intervention. The chance of seizure
recurrence leading to ER visit decreased with age and increased with the number
of comorbidities. Patients with seizure recurrence were more likely to be taking
an enzyme-inducing AED (OR 1.69, 95%CI 1.57-1.82) and receiving Part D Low Income
Subsidy (OR 1.36, 95%CI 1.22-1.51). The probability of AED change after a seizure
was higher for patients with >=4 comorbidities (OR 1.69, 95%CI 1.25-2.27),
patients who saw a neurologist (OR 1.49, 95%CI 1.30-1.70), and patients who were
taking an enzyme-inducing AED (OR 1.47, 95%CI 1.27-1.71). Overall, a minority of
Medicare beneficiaries experienced seizure recurrence that resulted in an ER
visit. However, only half of them received treatment concordant with QUIET-15.
Though racial differences were observed in occurrence of seizures, none were
noted in the provision of care.
PMID- 28412155
TI - Ascorbic acid inhibits human insulin aggregation and protects against amyloid
induced cytotoxicity.
AB - Protein aggregation into oligomers and fibrils are associated with many human
pathophysiologies. Compounds that modulate protein aggregation and interact with
preformed fibrils and convert them to less toxic species, expect to serve as
promising drug candidates and aid to the drug development efforts against
aggregation diseases. In present study, the kinetics of amyloid fibril formation
by human insulin (HI) and the anti-amyloidogenic activity of ascorbic acid (AA)
were investigated by employing various spectroscopic, imaging and computational
approaches. We demonstrate that ascorbic acid significantly inhibits the
fibrillation of HI in a dose-dependent manner. Interestingly ascorbic acid
destabilise the preformed amyloid fibrils and protects human neuroblastoma cell
line (SH- SY5Y) against amyloid induced cytotoxicity. The present data signifies
the role of ascorbic acid that can serve as potential molecule in preventing
human insulin aggregation and associated pathophysiologies.
PMID- 28412156
TI - Tyrosine oxidation and nitration in transmembrane peptides is connected to lipid
peroxidation.
AB - Tyrosine nitration is an oxidative post-translational modification that can occur
in proteins associated to hydrophobic bio-structures such as membranes and
lipoproteins. In this work, we have studied tyrosine nitration in membranes using
a model system consisting of phosphatidylcholine liposomes with pre-incorporated
tyrosine-containing 23 amino acid transmembrane peptides. Tyrosine residues were
located at positions 4, 8 or 12 of the amino terminal, resulting in different
depths in the bilayer. Tyrosine nitration was accomplished by exposure to
peroxynitrite and a peroxyl radical donor or hemin in the presence of nitrite. In
egg yolk phosphatidylcholine liposomes, nitration was highest for the peptide
with tyrosine at position 8 and dramatically increased as a function of oxygen
levels. Molecular dynamics studies support that the proximity of the tyrosine
phenolic ring to the linoleic acid peroxyl radicals contributes to the efficiency
of tyrosine oxidation. In turn, alpha-tocopherol inhibited both lipid
peroxidation and tyrosine nitration. The mechanism of tyrosine nitration involves
a "connecting reaction" by which lipid peroxyl radicals oxidize tyrosine to
tyrosyl radical and was fully recapitulated by computer-assisted kinetic
simulations. Altogether, this work underscores unique characteristics of the
tyrosine oxidation and nitration process in lipid-rich milieu that is fueled via
the lipid peroxidation process.
PMID- 28412157
TI - Are we ready for a "tissue identity card" of inherited cardiomyopathies?
PMID- 28412160
TI - Study design for vulnerable older adults with multiple myeloma.
PMID- 28412159
TI - Synthesis and evaluation of a series of pyridine and pyrimidine derivatives as
type II c-Met inhibitors.
AB - In this study, a series of novel pyridine and pyrimidine-containing derivatives
were designed, synthesized and biologically evaluated for their c-Met inhibitory
activities. In the biological evaluation, half of the target compounds exhibited
moderate to potent c-Met inhibitory activities. Among which, it is noteworthy
that compounds 13d not only showed most potent c-Met inhibitory potency but also
displayed excellent anti-proliferative activity (IC50=127nM against EBC-1 cell
line) as well as an acceptable kinase selectivity profile. Moreover, the western
blot assay indicated that 13d inhibited c-Met phosphorylation in EBC-1 cells in a
dose-dependent manner, with complete abolishment at 0.1mM. All these experimental
results suggested that 13d could be served as a promising lead compound for the
development of anticancer agents.
PMID- 28412158
TI - Lidocaine attenuation testing: An in vivo investigation of putative LQT3
associated variants in the SCN5A-encoded sodium channel.
AB - BACKGROUND: Long QT syndrome type 3 (LQT3) accounts for 5%-10% of long QT
syndrome and results from gain-of-function mutations in the SCN5A-encoded sodium
channel. Approximately 2% of healthy individuals host rare SCN5A variants of
uncertain significance (VUS). Distinction of true LQT3-causative mutations from
background genetic noise is essential. OBJECTIVE: The purpose of this study was
to assess the use of the lidocaine attenuation test (LAT) in evaluating patients
with possible LQT3. METHODS: We reviewed the LAT results and medical records for
25 patients with a possible LQT3-associated SCN5A variant. The LAT involved a
loading dose of 1 mg/kg of intravenous lidocaine followed by continuous infusion
at 50 MUg/(kg?min) for 20 minutes. If the corrected QT interval shortened by >=30
ms, the LAT was defined as positive. RESULTS: Sixteen patients (64%) had a
positive LAT, 6 of which demonstrated the E1784K variant. A positive LAT
correlated in 86% of cases with abnormal in vitro channel function (mean
corrected QT interval attenuation 43 +/- 3 ms vs 25 +/- 5 ms for wild-type
variants; P = .03). Four of 5 patients (80%) with a VUS had a positive LAT
(T1304M [2 patients], L1786P, and R800L). The T1304M variant demonstrated
abnormal in vitro function and a positive LAT, opening the door for a potential
variant promotion from VUS to likely pathogenic. CONCLUSION: The LAT may help
distinguish true LQT3-causative mutations from an otherwise noncontributory VUS.
Given that lidocaine acts as a late sodium current blocker, a positive LAT may
enable the early identification of a pathological accentuation of the late sodium
current that could be targeted therapeutically.
PMID- 28412161
TI - The effect of the apneic period on the respiratory physiology of patients
undergoing intubation in the ED.
AB - OBJECTIVES: We sought to examine the physiological impact the apneic period has
on the respiratory physiology of patients undergoing intubation in the emergency
department and whether DAO, the delivery of 15L oxygen by nasal cannula during
apnea, can affect the development of respiratory acidosis. METHODS: This was a
prospective observational cohort study conducted at an urban academic level 1
trauma center. A convenience sample of 100 patients was taken. Timed data
collection forms were completed during the periintubation period. We report the
mean ABG and end-tidal CO2 (EtCO2) values between those with normal and prolonged
apnea times (>60s) and between those who received DAO and those who did not.
RESULTS: 100 patients met our inclusion criteria. There were no significant
differences in the pre-RSI ABG values between those who received DAO and those
who did not and between those with apnea times less than or >60s. Only in the
group of patients with apnea times >60s did significant changes in respiratory
physiology occur. DAO did not alter the trend in respiratory acidosis during the
periintubation period. EtCO2 increased as apnea times were prolonged, and DAO
altered this trend. CONCLUSIONS: Post-RSI EtCO2 increased as apnea times were
prolonged. DAO may alter this trend. Statistically significant changes in pH and
PaCO2 (mean differences of 0.15 and 12.5, respectively) occurred in the group of
patients who had mean apnea times of >60s but not in those with apnea times <60s.
PMID- 28412162
TI - Incidence and clinical features of sacral insufficiency fracture in the emergency
department.
AB - INTRODUCTION: A sacral insufficiency fracture (SIF) often manifests as low back
pain or sciatica in the absence of any antecedent trauma. These fractures may be
missed because of lack of appropriate imaging. The purpose of this study was to
clarify the incidence and clinical features of SIF as well as the characteristic
findings on magnetic resonance imaging (MRI) of the lumbar spine. MATERIALS AND
METHODS: The study participants comprised 250 patients (132 male, 118 female;
mean age 58.6years) with pelvic trauma. SIF was identified on computed tomography
or MRI. The incidence, initial symptoms, and time delay between the first visit
and an accurate diagnosis of SIF were recorded. RESULTS: We detected 11 cases of
SIF. Initial symptoms of SIF were low back pain (36.4%), gluteal pain (63.6%),
and coxalgia (18.2%). Two patients complained of both low back pain and gluteal
pain. The mean delay between the first visit and an accurate diagnosis of SIF was
23.9days. This time interval was significantly longer than in patients with other
types of pelvic fracture. Four patients underwent MRI targeting the lumbar spine
to investigate their symptoms. In all 4 patients, the signal intensity on T1
weighted and fat-suppressed images of the second sacral segment was low and high,
respectively. CONCLUSION: This study demonstrates that accurate diagnosis of SIF
may be delayed because of difficulties in detecting this type of fracture on
plain X-ray and the non-specific nature of the presenting complaints. Emergency
physicians should keep SIF in mind when investigating patients who complain of
low back pain or gluteal pain. Findings at the second sacral segment on MRI
targeting the lumbar spine may aid early diagnosis of this type of pelvic
fracture.
PMID- 28412163
TI - Electroencephalographic responses of anaesthetized pigs (Sus scrofa) to tail
docking using clippers or cautery iron performed at 2 or 20 days of age.
AB - OBJECTIVE: To compare electroencephalographic (EEG) responses of pigs to tail
docking using clippers or cautery iron, performed at 2 or 20 days of age. STUDY
DESIGN: Prospective, randomised controlled experimental study. ANIMALS: A total
of 40 Large White x Landrace entire male pigs aged 2 (n=20) or 20 (n=20) days
were randomly assigned to undergo tail docking using clippers or cautery iron.
METHODS: Anaesthesia was induced and maintained with halothane delivered in
oxygen. Following instrumentation, end-tidal halothane concentration was
stabilised at 1.0+/-0.05%, and EEG recording commenced. After a 5 minute baseline
period, tail docking was performed and recording continued for additional 10
minutes. EEG data were subjected to Fast Fourier transformation, yielding the
summary variables median frequency (F50), 95% spectral edge frequency (F95) and
total power (PTOT). Variables recorded during the baseline period were compared
with those calculated at consecutive 15 second intervals following tail docking.
RESULTS: Following tail docking, F50 decreased briefly but significantly in 2-day
olds, whereas 20-day-olds exhibited a sustained increase in F50 (p<0.05).
Immediately after tail docking, F50 was overall lower in 2-day-olds than in 20
day-olds (p<0.05). F95 increased after docking in 20-day-olds docked using
clippers (p<0.05) but did not change in 20-day-olds docked using cautery iron or
in 2-day-olds docked using either method. Overall, F95 was lower in 2-day-olds
than in 20-day-olds from 30 to 60 seconds after docking (p<0.05). PTOT decreased
after docking in 20-day-olds (p<0.05) but did not change in 2-day-olds. Overall,
PTOT was lower in 2- than in 20-day-olds during baseline and after tail docking
(p<0.05). CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that tail
docking using clippers is more acutely painful than docking using cautery iron
and that docking within the first days of birth may be less acutely painful than
docking at a later age.
PMID- 28412164
TI - Diagnosis and Management of Oropharyngeal Dysphagia Among Older Persons, State of
the Art.
AB - Oropharyngeal dysphagia (OD) is a condition recognized by the World Health
Organization and defined as the difficulty or inability to move a bolus safely
and effectively from the oral cavity to the esophagus, and can include
aspirations, choking, and residue. OD is pandemic among different phenotypes of
older people, affecting between 27% and 91% of the population 70 years or older.
Although OD can be diagnosed by well-defined clinical methods and complementary
explorations, in the clinical setting OD is seldom systematically screened and
treated, and awareness among the medical/geriatric community is scarce. The
etiology of OD in this population includes many concomitant risk factors with
neurogenic and neurodegenerative processes, muscular weakness, and sarcopenia.
The pathophysiology includes mechanical deficits in the swallow response (mainly
delayed laryngeal vestibule closure time and weak tongue thrust), reduced
pharyngeal sensitivity, and sensory/motor central nervous system impairments.
Recently, OD has been recognized as a geriatric syndrome due to its high
prevalence and its relationship with many comorbidities and their poor outcomes,
including malnutrition, respiratory infections and aspiration pneumonia,
functional disability and frailty, institutionalization and increased
readmissions, and mortality. There is an evidence-based and effective treatment
for OD in the elderly mainly oriented to compensating swallow impairments through
adaptation of fluid viscosity and solid food textures to avoid aspiration and
choking, and improving nutritional status and oral health to avoid respiratory
infections. This has been defined as the minimal effective treatment to be
provided to this population. New treatments aiming at recovering the swallowing
function are under research with promising results, and the near future will
provide us with methods to stimulate the swallow response with pharmacological or
physical stimuli.
PMID- 28412165
TI - Effects of a Community-Based Program for Oral Health and Nutrition on Cost
Effectiveness by Preventing Disability in Japanese Frail Elderly: A Quasi
Experimental Study Using Propensity Score Matching.
AB - OBJECTIVE: In the Japanese Long-Term Care Insurance (LTCI) system, a community
based program for oral health and nutrition (OHN program) has been implemented
with the aim of reducing incident disability and care costs. However, the
effectiveness of this program has not been confirmed epidemiologically. The
purpose of the present study was to test the hypothesis that the OHN program does
reduce incident disability and care costs. DESIGN: A prospective study with a 28
month follow-up period was conducted using data from administrative databases at
Tagajo City, Japan. Among frail elderly persons (aged 65 years or more) who were
enrolled in the LTCI program in Tagajo, 64 participants in the OHN program and
128 controls (nonparticipants) were selected by propensity score matching.
MEASUREMENTS: We used 2 types of outcome measure: composite outcome (incident
disability and death) and care cost. Data on incident disability were retrieved
from the public LTCI database. Care cost was defined as the total amount of LTCI
service cost added to medical care cost. RESULTS: The hazard ratio of composite
outcome was significantly lower for the intervention group than for the control
group (hazard ratio = 0.32, 95% confidence interval 0.12-0.82). Even when we set
incident disability as an outcome, the hazard ratio for the intervention group
did not change (hazard ratio = 0.33, 95% confidence interval 0.11-0.97). The mean
cumulative care cost during the 28 months tended to be lower for the intervention
group ($4893) than that for the control group ($5770), but this was not
statistically significant by the gamma regression model (cost ratio = 0.85, P =
.513). The mean care cost per unit follow-up period (1 month) for the
intervention group was significantly lower (cost ratio = 0.54, P = .027).
CONCLUSIONS: The results of this study suggest that the OHN program is effective
for preventing incident disability and, consequently, for saving care costs per
unit survival period.
PMID- 28412166
TI - Palliative Care Development in European Care Homes and Nursing Homes: Application
of a Typology of Implementation.
AB - BACKGROUND: The provision of institutional long-term care for older people varies
across Europe reflecting different models of health care delivery. Care for dying
residents requires integration of palliative care into current care work, but
little is known internationally of the different ways in which palliative care is
being implemented in the care home setting. OBJECTIVES: To identify and classify,
using a new typology, the variety of different strategic, operational, and
organizational activities related to palliative care implementation in care homes
across Europe. DESIGN AND METHODS: We undertook a mapping exercise in 29 European
countries, using 2 methods of data collection: (1) a survey of country
informants, and (2) a review of data from publically available secondary data
sources and published research. Through a descriptive and thematic analysis of
the survey data, we identified factors that contribute to the development and
implementation of palliative care into care homes at different structural levels.
From these data, a typology of palliative care implementation for the care home
sector was developed and applied to the countries surveyed. RESULTS: We
identified 3 levels of palliative care implementation in care homes: macro
(national/regional policy, legislation, financial and regulatory drivers), meso
(implementation activities, such as education, tools/frameworks, service models,
and research), and micro (palliative care service delivery). This typology was
applied to data collected from 29 European countries and demonstrates the
diversity of palliative care implementation activity across Europe with respect
to the scope, type of development, and means of provision. We found that macro
and meso factors at 2 levels shape palliative care implementation and provision
in care homes at the micro organizational level. CONCLUSIONS: Implementation at
the meso and micro levels is supported by macro-level engagement, but can happen
with limited macro strategic drivers. Ensuring the delivery of consistent and
high-quality palliative care in care homes is supported by implementation
activity at these 3 levels. Understanding where each country is in terms of
activity at these 3 levels (macro, meso, and micro) will allow strategic focus on
future implementation work in each country.
PMID- 28412167
TI - Mortality in Nursing Homes Following Emergency Evacuation: A Systematic Review.
AB - OBJECTIVES: To determine the risk associated with mortality among nursing home
residents within 6 months following an evacuation because of man-made or natural
disasters. DESIGN: A systematic review conducted in accordance with the Preferred
Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement.
SETTING: All peer-reviewed studies published in English, French, German, or
Spanish between January 1, 2000 and December 31, 2015, examining mortality within
6 months of disaster evacuation from a nursing home. MEASUREMENTS: Extracted
information included study and population characteristics, mortality measures,
and risk factors. Studies were examined using the disaster management cycle that
considers preparedness, response, recovery, and mitigation. RESULTS: The 10
included studies were published between 2010 and 2015 with one-half conducted in
the United States. Only 3 studies detailed the preparedness stage, and 4 detailed
the response stage of the disaster management cycle. Mortality was measured as an
indicator of recovery and was found to be elevated at 1 month [from 0.03% (n =
1088) to 10.5% (n = 75)] 3 months [from 0.08% (n = 3091) to 15.2% (n = 197)], and
6 months [from 14.9% (n = 263) and 16.8% (n = 22)] postevacuation compared with
pre-evacuation and sheltering-in-place. Studies identified vulnerable residents
as being over 80 years of age, frail, dependent, male residents with multiple
comorbidities and, made recommendations on disaster preparedness. CONCLUSIONS:
There is little research on the effects of evacuation on nursing home residents,
which is surprising considering the elevated risk of mortality postevacuation.
Evacuation seems to have a negative effect on the survival of nursing home
residents independent of the effect of the disaster. Standard evacuation
procedures may be less applicable to this vulnerable population because of extra
challenges they face in disasters.
PMID- 28412168
TI - Facilitating Translational Nanomedicine via Predictive Safety Assessment.
AB - Extensive research on engineered nanomaterials (ENMs) has led to the development
of numerous nano-based formulations for theranostic purposes. Although some nano
based drug delivery systems already exist on the market, growing numbers of newly
designed ENMs exhibit improved physicochemical properties and are being assessed
in preclinical stages. While these ENMs are designed to improve the efficacy of
current nano-based therapeutic or imaging systems, it is necessary to thoroughly
determine their safety profiles for successful clinical applications. As such,
our aim in this mini-review is to discuss the current knowledge on predictive
safety and structure-activity relationship (SAR) analysis of major ENMs at the
developing stage, as well as the necessity of additional long-term toxicological
analysis that would help to facilitate their transition into clinical practices.
We focus on how the interaction of these nanomaterials with cells would trigger
signaling pathways as molecular initiating events that lead to adverse outcomes.
These mechanistic understandings would help to design safer ENMs with improved
therapeutic efficacy in clinical settings.
PMID- 28412169
TI - Engineered Exosomes as Vehicles for Biologically Active Proteins.
AB - Exosomes represent an attractive vehicle for the delivery of biomolecules.
However, mechanisms for loading functional molecules into exosomes are relatively
unexplored. Here we report the use of the evolutionarily conserved late-domain (L
domain) pathway as a mechanism for loading exogenous proteins into exosomes. We
demonstrate that labeling of a target protein, Cre recombinase, with a WW tag
leads to recognition by the L-domain-containing protein Ndfip1, resulting in
ubiquitination and loading into exosomes. Our results show that Ndfip1 expression
acts as a molecular switch for exosomal packaging of WW-Cre that can be
suppressed using the exosome inhibitor GW4869. When taken up by floxed reporter
cells, exosomes containing WW-Cre were capable of inducing DNA recombination,
indicating functional delivery of the protein to recipient cells. Engineered
exosomes were administered to the brain of transgenic reporter mice using the
nasal route to test for intracellular protein delivery in vivo. This resulted in
the transport of engineered exosomes predominantly to recipient neurons in a
number of brain regions, including the olfactory bulb, cortex, striatum,
hippocampus, and cerebellum. The ability to engineer exosomes to deliver
biologically active proteins across the blood-brain barrier represents an
important step for the development of therapeutics to treat brain diseases.
PMID- 28412170
TI - Lipid Nanoparticle Systems for Enabling Gene Therapies.
AB - Genetic drugs such as small interfering RNA (siRNA), mRNA, or plasmid DNA provide
potential gene therapies to treat most diseases by silencing pathological genes,
expressing therapeutic proteins, or through gene-editing applications. In order
for genetic drugs to be used clinically, however, sophisticated delivery systems
are required. Lipid nanoparticle (LNP) systems are currently the lead non-viral
delivery systems for enabling the clinical potential of genetic drugs.
Application will be made to the Food and Drug Administration (FDA) in 2017 for
approval of an LNP siRNA drug to treat transthyretin-induced amyloidosis,
presently an untreatable disease. Here, we first review research leading to the
development of LNP siRNA systems capable of silencing target genes in hepatocytes
following systemic administration. Subsequently, progress made to extend LNP
technology to mRNA and plasmids for protein replacement, vaccine, and gene
editing applications is summarized. Finally, we address current limitations of
LNP technology as applied to genetic drugs and ways in which such limitations may
be overcome. It is concluded that LNP technology, by virtue of robust and
efficient formulation processes, as well as advantages in potency, payload, and
design flexibility, will be a dominant non-viral technology to enable the
enormous potential of gene therapy.
PMID- 28412172
TI - New yeast models for studying mitochondrial morphology as affected by oxidative
stress and other factors.
AB - The overwhelming majority of investigations on mitochondrial morphology were
performed using S. cerevisiae. In this study we showed the benefits of applying
new model organisms including petite-negative D. magnusii and Y. lipolytica
yeasts for visualization of mitochondrial fragmentation. Normally giant D.
magnusii cells and filament-like Y. lipolytica cells contain the highly
structured mitochondrial reticulum. Oxidative stress mediated by tert-butyl
hydroperoxide triggered mitochondrial fragmentation in yeasts. In D. magnusii
mitochondrial fragmentation was also induced by impairing the oxidative
phosphorylation system. Higher prooxidant concentrations caused cell death.
Cationic lipophilic antioxidant SkQ1 acted downstream of the excessive ROS
production and prevented partially or almost totally oxidative stress and related
mitochondrial fragmentation and cell death. We believe that utility of D.
magnusii and Y. lipolytica yeasts as a "living test tube" would be useful for
providing new information concerning the interplay between mitochondrial dynamics
and mitochondrial dysfunction, cell cycle, aging, mitophagy and cell death.
PMID- 28412171
TI - Gender-Specific Amelioration of SMA Phenotype upon Disruption of a Deep Intronic
Structure by an Oligonucleotide.
AB - Spinal muscular atrophy (SMA), the leading genetic disease of children, is caused
by low levels of survival motor neuron (SMN) protein. Here, we employ A15/283, an
antisense oligonucleotide targeting a deep intronic sequence/structure, to
examine the impact of restoration of SMN in a mild SMA mouse model. We show
gender-specific amelioration of tail necrosis upon subcutaneous administrations
of A15/283 into SMA mice at postnatal days 1 and 3. We also demonstrate that a
modest increase in SMN due to early administrations of A15/283 dramatically
improves testicular development and spermatogenesis. Our results reveal near
total correction of expression of several genes in adult testis upon temporary
increase in SMN during early postnatal development. This is the first
demonstration of in vivo efficacy of an antisense oligonucleotide targeting a
deep intronic sequence/structure. This is also the first report of gender
specific amelioration of SMA pathology upon a modest peripheral increase of SMN.
PMID- 28412174
TI - Experimentally determined tilt and bending moduli of single-component lipid
bilayers.
AB - Values of the bending modulus KC and the tilt modulus Ktheta are reported for
single component lipid bilayers. The lipids studied have the common names DOPC,
DMPC, diC22:1PC, SOPC, POPC, diPhyPC, DLPC, DPPC, DHPC and DEPC, listed in the
order of number of samples examined. The experimental method, thus far the only
one that measures the tilt modulus of lipid bilayers, first obtains diffuse X-ray
scattering data from oriented stacks of bilayers. The values of the moduli emerge
from fitting the data to the accepted tilt-dependent continuum model for the free
energy of a single bilayer, further enhanced by interactions between bilayers in
the stack. The results indicate the broad trend that the tilt modulus for these
PC lipids is smaller the closer the temperature is to the main transition
temperature. Another trend is that inclusion of tilt raises the value of the
bending modulus more for lipids with smaller values of the tilt modulus. Values
of both moduli are compared to recent literature values obtained from simulations
and values of the bending modulus are compared to the literature values obtained
by other experimental methods.
PMID- 28412173
TI - Spontaneous formation of single component liposomes from a solution.
AB - The diameter of lipid vesicles is generally known to be determined by parameters
external to the system, such as fluid shear, electric fields, co-surfactants,
etc. We present a mechanism by which a system consisting of a single component
lipid can spontaneously assemble from a solution phase to form monodisperse
unilamellar vesicles of well-defined diameters dictated only by thermodynamic
parameters intrinsic to the system. Here, the lipids self-assemble as vesicles
when an aqueous phase diffusively replaces the original solvent in a
macroscopically stationary (or quiescent) manner. We demonstrate this using
phosphatidyl choline lipid-ethanol-water systems, where the average diameter of
the liposomes is shown to be intrinsic, in reasonable agreement with the
Helfrich's model of the vesicle free energy. The size depends only on the
temperature and the lipid type, eliminating dependence on kinetic effects or
external forcing normally observed. The method provides the first pure system to
study the self-assembly of vesicle-forming surfactants; and with a natural
thermodynamic length scale, it may have an implication for the vesicle size
selection under pre-biotic conditions.
PMID- 28412175
TI - Legionnaires' disease from a dental unit. Chicken-and-egg or a different source
entirely?
PMID- 28412177
TI - Educational programme to enhance stethoscope hygiene behaviour.
PMID- 28412176
TI - Human parvovirus B19 nosocomial outbreak in healthcare personnel in a paediatric
ward at a national tertiary referral centre in Thailand.
AB - BACKGROUND: Nosocomial outbreaks of parvovirus B19 (pB19) have been reported, but
they rarely occur among healthcare personnel (HCP). Susceptibility among pregnant
HCP was the major concern. METHODS: An outbreak of pB19 among HCP is described in
a paediatric ward with a cross-sectional serologic study in all HCP and patients
exposed to the outbreak. Acute infection was diagnosed by polymerase chain
reaction or positive anti-parvovirus B19 IgM. FINDINGS: Among 48 HCP (three
pregnant) and 22 patients included in the outbreak serologic study, 11 (23%) HCP
and two (9%) patients had acute infection. Of these, six HCP and no patients were
symptomatic. Clinical manifestations included itchy rash (100%) and joint pain
following resolution of rash (67%), with median rash duration of four days. Forty
percent of HCP and 50% of patients had positive anti-parvovirus IgG, indicating
previously immune status. HCP with acute infection and HCP who were susceptible
without infection were younger than HCP with previous immunity (mean age 32.2 vs
40.5 years, respectively; P = 0.003). The attack rate was 38% among HCP and 18%
among patients who were susceptible, respectively. The outbreak ended within two
weeks following strict droplet precaution and segregation of symptomatic HCP.
CONCLUSION: Parvovirus B19 infection may cause nosocomial outbreak with high
attack rate among HCP. Outbreak control with droplet precaution was highly
effective.
PMID- 28412178
TI - Universal screening and decolonization for control of MRSA in nursing homes:
follow-up of a cluster randomized controlled trial.
AB - In 2010-11, a trial conducted in nursing homes showed no benefit of meticillin
resistant Staphylococcus aureus (MRSA) universal screening and decolonization
over standard precautions to reduce the prevalence of MRSA carriage. Accordingly,
no routine screening was performed from 2012. A five-year follow-up shows no new
evidence supporting the intervention. Recommendations issued after trial (no
screening and decolonization of MRSA residents) were retained.
PMID- 28412179
TI - Unsafe waste management practices and hepatitis C among hospital sanitary staff
in Pakistan.
PMID- 28412180
TI - Computational fluid dynamics study of the pharyngeal airway space before and
after mandibular setback surgery in patients with mandibular prognathism.
AB - The purpose of this study was to investigate the relationship between the
pressure drop in the pharyngeal airway space (DeltaPPAS) and the minimum cross
sectional area (minCSA) of the pharyngeal airway before and after mandibular
setback surgery using computational fluid dynamics, in order to prevent
iatrogenic obstructive sleep apnoea. Eleven patients with mandibular prognathism
underwent bilateral sagittal split osteotomy for mandibular setback. Three
dimensional models of the upper airway were reconstructed from preoperative and
postoperative computed tomography images, and simulations were performed using
computational fluid dynamics. DeltaPPAS and the minCSA of the pharyngeal airway
were calculated, and the relationship between them was evaluated by non-linear
regression analysis. In all cases, the minCSA was found at the level of the
velopharynx. After surgery, DeltaPPAS increased significantly and the minCSA
decreased significantly. The non-linear regression equation expressing the
relationship between these variables was DeltaPPAS=3.73*minCSA-2.06. When the
minCSA was <1cm2, DeltaPPAS increased greatly. The results of this study suggest
that surgeons should consider bimaxillary orthognathic surgery rather than
mandibular setback surgery to prevent the development of iatrogenic obstructive
sleep apnoea when correcting a skeletal class III malocclusion.
PMID- 28412181
TI - Maxilla reconstruction with autogenous bone block grafts: computed tomography
evaluation and implant survival in a 5-year retrospective study.
AB - This retrospective study was performed to evaluate the bone thickness of the
anterior maxillary region after reconstruction with autogenous bone blocks at 6
months and 5 years after surgery using computed tomography (CT) and to determine
the implant survival rate. Eleven patients with a horizontal bone deficiency were
treated with reconstructive procedures and implant placement. CT measurements
were obtained before surgery (T0) and at 6 months (T1) and 5 years (T2) after
surgery. The values were analysed statistically (analysis of variance and Tukey's
test; P<0.05). Implant survival was evaluated at follow-up. The mean width of the
lower region of the ridge (+/-standard deviation, in millimetres) was 3.8+/-1.6
at T0, 7.0+/-1.6 at T1, and 6.5+/-1.0 at T2; the mean width of the upper region
of the ridge was 5.7+/-2.3 at T0, 8.3+/-2.2 at T1, and 7.3+/-1.6 at T2. The mean
total thickness of the ridge was 4.7mm at T0, 7.6mm at T1, and 6.9mm at T2; the
average increase in horizontal thickness was 2.9mm at T1 and 2.2mm at T2. A
statistically significant difference was observed in the mean width of the lower
portion at T1 and T2 compared to the width at T0. The implant survival rate was
94.1%. This technique demonstrated high predictability for implant survival, with
a reduction in the graft bone during the follow-up period.
PMID- 28412182
TI - Characterization of three small molecule inhibitors of enterovirus 71 identified
from screening of a library of natural products.
AB - Enterovirus 71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD).
Infection with EV-A71 is more often associated with neurological complications in
children and is responsible for the majority of fatalities, but currently there
is no approved antiviral therapy for treatment. Here, we identified auraptene,
formononetin, and yangonin as effective inhibitors of EV-A71 infection in the low
micromolar range from screening of a natural product library. Among them,
formononetin and yangonin selectively inhibited EV-A71 while auraptene could
inhibit viruses within the enterovirus species A. Time of addition studies showed
that all the three inhibitors inhibit both attachment and postattachment step of
entry. We found mutations conferring the resistance to these inhibitors in the
VP1 and VP4 capsid proteins and confirmed the target residues using a reverse
genetic approach. Interestingly, auraptene- and formononetin-resistant viruses
exhibit cross-resistance to other inhibitors while yangonin-resistant virus still
remains susceptible to auraptene and formononetin. Moreover, auraptene and
formononetin, but not yangonin protected EV-A71 against thermal inactivation,
indicating a direct stabilizing effect of both compounds on virion capsid
conformation. Finally, neither biochanin A (an analog of formononetin) nor DL
Kavain (an analog of yangonin) exhibited anti-EV-A71 activity, suggesting the
structural elements required for anti-EV-A71 activity. Taken together, these
compounds could become potential lead compounds for anti-EV-A71 drug development
and also serve as tool compounds for studying virus entry.
PMID- 28412184
TI - Clinical trial research in focus: why do so many clinical trials fail in IPF?
PMID- 28412183
TI - Structure-activity relationship analysis of mitochondrial toxicity caused by
antiviral ribonucleoside analogs.
AB - Recent cases of severe toxicity during clinical trials have been associated with
antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have
hypothesized that the active metabolites of toxic ribonucleoside analogs, the
triphosphate forms, inadvertently target human mitochondrial RNA polymerase
(POLRMT), thus inhibiting mitochondrial RNA transcription and protein synthesis.
Others have proposed that the prodrug moiety released from the ribonucleoside
analogs might instead cause toxicity. Here, we report the mitochondrial effects
of several clinically relevant and structurally diverse ribonucleoside analogs
including NITD-008, T-705 (favipiravir), R1479 (parent nucleoside of
balapiravir), PSI-7851 (sofosbuvir), and INX-08189 (BMS-986094). We found that
efficient substrates and chain terminators of POLRMT, such as the nucleoside
triphosphate forms of R1479, NITD-008, and INX-08189, are likely to cause
mitochondrial toxicity in cells, while weaker chain terminators and inhibitors of
POLRMT such as T-705 ribonucleoside triphosphate do not elicit strong in vitro
mitochondrial effects. Within a fixed 3'-deoxy or 2'-C-methyl ribose scaffold,
changing the base moiety of nucleotides did not strongly affect their inhibition
constant (Ki) against POLRMT. By swapping the nucleoside and prodrug moieties of
PSI-7851 and INX-08189, we demonstrated that the cell-based toxicity of INX-08189
is mainly caused by the nucleoside component of the molecule. Taken together,
these results show that diverse 2' or 4' mono-substituted ribonucleoside
scaffolds cause mitochondrial toxicity. Given the unpredictable structure
activity relationship of this ribonucleoside liability, we propose a rapid and
systematic in vitro screen combining cell-based and biochemical assays to
identify the early potential for mitochondrial toxicity.
PMID- 28412185
TI - Coexistence of risk behaviors for being overweight among Brazilian adolescents.
AB - This study aimed to evaluate the magnitude of and the factors associated with the
coexistence of risk behaviors for being overweight among Brazilian adolescents.
This is a cross-sectional study with a representative sample of adolescents
(mostly aged 13-15years) enrolled from public and private schools of Brazil in
2012. The co-occurring sedentary behavior and inadequate food consumption
(regular intake of sugary and fried foods, and irregular consumption of fruits
and vegetables-FV) was estimated using a Venn diagram. Sociodemographic,
familial, and behavioral factors associated with the number of risk behaviors for
being overweight were identified using an ordinal logistic regression analysis.
Sedentary behavior was observed in 62.0% of adolescents. Regular intake of sugary
or fried food was observed in 55.3% and 23.5% of adolescents, respectively, with
51.9% having an inadequate intake of FV. At least one risk behavior was reported
in >90.0% of adolescents; 6.1% reported all 4. Being female, having a higher
maternal education level, attending private school, not having breakfast or meals
with parents regularly, eat watching television, and not practicing weekly
leisure time physical activity were associated with an increased chance of having
multiple risk behaviors. This study observed a high prevalence of coexisting of
risk behaviors, which was associated with sociodemographic, familial, and
behavioral factors. These findings may contribute to a clearer understanding of
the associations between different behaviors among adolescents, and may be used
to improve public health surveillance and to develop strategies that address
multiple behaviors, in order to prevent overweight among adolescents.
PMID- 28412186
TI - Cardiorespiratory fitness, physical activity and cancer mortality in men.
AB - The preventive role of cardiorespiratory fitness (CRF) and physical activity (PA)
in cancer mortality is not well-established. This study sought to evaluate the
association between CRF, PA and cancer mortality in men. Maximal exercise testing
was performed at the VA Palo Alto Health Care System in 5876 male veterans
(60.5+/-11years) free from malignancy at baseline who were followed for mean of
9.9 (range 0.11 to 26.8) years. PA status was assessed in a sub-group of 4034
participants. Relative risks and population attributable risks (PAR%) for cancer
related mortality were determined. During the follow-up, 447 men (7.6%) died from
cancer. Forty-nine percent of the sample was considered physically active
(defined as meeting the minimal PA guidelines); this group exhibited a 20%
reduction in cancer mortality risk [95% confidence interval (0.67-0.97), p=0.02].
CRF was inversely associated with cancer death. For each 1 MET increase in CRF
there was a 5% reduction in risk for cancer mortality (p=0.01). Compared to the
least fit group (<5.0 METs), subjects with moderate to high CRF exhibited 26-46%
reduced risks of cancer mortality (p for trend=0.002). The PARs% for low CRF and
inactivity were 6.6% and 8.5%, respectively. Moderate and high CRF levels and
meeting the minimal PA guidelines have protective benefits against cancer
mortality in men. Eliminating inactivity and low CRF as risk factors could
potentially prevent a considerable number of cancer deaths and reduce the
associated societal and economic burden.
PMID- 28412187
TI - Restoring Volar Tilt in AO Type C2 Fractures of the Distal Radius With Unilateral
External Fixation.
AB - PURPOSE: To determine whether unilateral external fixation using a staged
multiplanar reduction technique restores anatomic volar tilt in a distal radius
fracture model. METHODS: We used radiographic images to obtain baseline
measurements in 20 fresh-frozen cadaveric wrists. Through a standard dorsal
approach to the radius, we performed osteotomies to simulate displaced AO/ASIF
type C2 fractures. After placement of a unilateral external fixator, a stepwise
technique of applying longitudinal traction followed by a volar translational
maneuver was performed. Radiographic imaging was obtained after each step of the
multiplanar reduction technique. RESULTS: Standard longitudinal traction did not
restore volar tilt angles to their baseline measurements. The addition of a volar
translation maneuver had a significant effect on restoring baseline volar tilt.
There was a statistically significant difference in volar tilt measurements
between straight longitudinal traction and volar translation. Radial inclination,
radial height, and ulnar variance did not differ significantly between
longitudinal traction and the addition of volar translation. CONCLUSIONS: A
criticism of traditional external fixation is the inability of longitudinal
ligamentotaxis to attain sagittal plane (volar tilt) reduction of the articular
surface. This study demonstrates that a multiplanar reduction technique using
unilateral external fixation devices on cadaveric distal radius fractures can
achieve an acceptable reduction. CLINICAL RELEVANCE: External fixation of distal
radius fractures may be favorable in situations where soft tissue loss, wound
contamination, and comorbid medical factors preclude the use of internal fixation
techniques. A multiplanar reduction technique using a unilateral external
fixation device may facilitate fracture reduction in acceptable alignment.
PMID- 28412188
TI - Patterns of Brachial Plexus Stretch Palsy in a Prospective Series of 565
Surgically Treated Patients.
AB - PURPOSE: To report the distribution of the different patterns of stretch brachial
plexus injuries (BPIs) in a retrospective cohort of patients operated at our
institution during an 11-year period. METHODS: From September 2002 to June 2012,
we evaluated and operated on 565 patients with traction injuries of the brachial
plexus. Average age was 26.8 years (SD +/-9.3 years); the interval between the
injury and surgery was 5.4 months (SD +/-2.8 months). The pattern of injury was
defined based on data obtained from a standardized clinical examination,
preoperative helical computed tomography myelography after intradural contrast
injection, surgical findings, and intraoperative electric stimulation. RESULTS:
Supraclavicular injuries accounted for 91% of all cases (N = 512) whereas 9% of
injuries were infraclavicular. Within the supraclavicular injuries, 50% of cases
involved the entire plexus and in 12% there was avulsion of all 5 roots. Among
them, 94% involved the upper plexus (C5 to C6 +/- C7 +/- C8), and 6% the lower
plexus (C8 to T1 +/- C7). C5 to C6 injuries accounted for 23% of partial BPI, C5
to C7 19%, C5 to C8 52%, C7 to T1 4%, and C8 to T1 2%. CONCLUSIONS: The most
relevant findings of this study were that most panplexal BPIs showed at least one
graftable root, there was a high prevalence of C5 to C8 BPI, C7 to T1 root injury
was the most common pattern of lower type of injury, and infraclavicular BPI was
uncommon. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.
PMID- 28412189
TI - Mean 5-Year Follow-up for Suture Button Suspensionplasty in the Treatment of
Thumb Carpometacarpal Joint Osteoarthritis.
AB - PURPOSE: Suture button suspensionplasty (SBS) has been used to treat thumb
carpometacarpal joint osteoarthritis (CMC joint OA). Although promising short
term outcomes have been reported, no outcomes beyond 4 years have been published.
The aim of this article is to report intermediate outcomes of SBS. METHODS: We
reviewed the charts of 14 patients who underwent 16 SBS procedures for
symptomatic thumb CMC joint OA. We recorded demographic data, preoperative Eaton
stage, length of follow-up, Quick-Disabilities of the Arm, Shoulder, and Hand
questionnaire scores, as well as pinch strength, grip strength, range of motion,
and metacarpal subsidence. Operative time and postoperative complications were
documented. RESULTS: Average age was 64 years. There were 12 women and 2 men.
Preoperative Eaton stages were III and IV in 8 thumbs each. Mean operative time
was 93 minutes. Mean follow-up was 64 months with mean Quick-Disabilities of the
Arm, Shoulder, and Hand score improvement of 58.2. Mean palmar and radial
abduction were 105% and 97%, respectively, of the nonsurgical thumb. Kapandji
scores for all operated thumbs were either 9 or 10. Pinch and grip strength were
107% and 102%, respectively, of the nonsurgical side. Mean trapezial space height
was 71%. One patient underwent removal of a symptomatic implant and 2 patients
had transient neuropraxia of the dorsal radial sensory nerve. CONCLUSIONS:
Favorable outcomes (improvement in range of motion and pain relief) of SBS remain
durable over time. Our results show that improvement in strength may also be
expected over time when using SBS after trapeziectomy for the treatment of thumb
CMC joint OA. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 28412190
TI - Exogenous growth factor based regenerative therapy in alcoholic cirrhosis
patients renders limited effect on hemostatic elements.
PMID- 28412191
TI - Red cell distribution width (RDW) is associated with cardiovascular disease risk
in Crohn's disease.
PMID- 28412192
TI - Association analysis of RAC1 single nucleotide polymorphisms with ulcerative
colitis.
PMID- 28412193
TI - Translational Research - Effective Communication and Teaching Strategies for
Improving the Quality of Pediatric Nursing Care for Hospitalized Children and
Their Families.
PMID- 28412194
TI - Parents find medical errors and safety incidents that hospitals miss.
PMID- 28412195
TI - Neutrophil-lymphocyte ratio predicts hospital-acquired bacterial infections in
decompensated cirrhosis.
AB - BACKGROUND: Bacterial infection is a frequent complication and severe burden in
cirrhotic patients. We determined the utility of neutrophil-to-lymphocyte ratio
(NLR) to predict the hospital-acquired (HA) bacterial infections episode in
patients with decompensated cirrhosis. METHODS: We retrospectively included 2066
consecutive decompensated cirrhotic patients from two separate tertiary
hospitals, divided into training (n=1377) and validation (n=689) set. All data
were collected on admission and all overt bacterial infections occurring after
>48h of hospital stay were registered. RESULTS: The incidence of HA bacterial
infections in training and validation cohort was 35.87% and 31.05% respectively.
Multivariate analysis showed that total bilirubin (TBil), albumin, white blood
cell count (WBC) and NLR were independent predictors of HA bacterial infections.
We established a Model_NTWA using these four variables and a Model_TWA which did
not include NLR. Areas under the curves (AUC) of Model_NTWA (0.859) and NLR
(0.824) were higher than which of Model_TWA (0.713), WBC (0.675), TBil (0.593)
and Albumin (0.583). Consistent with training cohort, validation cohort showed
similar results. Patients with NLR of at least 4.33 had a significantly lower
survival (P<0.001). CONCLUSIONS: NLR can be used as a novel noninvasive marker to
predict the occurrence of HA bacterial infections in decompensated cirrhotic
patients.
PMID- 28412196
TI - Non-enzymatic glycation enhances human serum albumin binding capacity to sodium
fluorescein at room temperature: A spectroscopic analysis.
AB - BACKGROUND: Sodium fluorescein (SF) is a fluorescent tracer dye used extensively
in diagnostic tools in the field of Ophthalmology, particularly in intravenous
fluorescein angiography (IVFA). The binding of SF to human serum albumin (HSA)
has been predicted by molecular docking and investigated by circular dichroism
(CD) and fluorescence spectroscopy with or without glycation at temperatures 296,
301, and 310K. METHODS: The binding parameters were calculated by quenching of
emission spectrum of a constant concentration of SF (2MUmol/l) at 513nm against
increasing concentrations of glycated or unmodified HSA as quencher starting from
stoichiometry ratio of 1:1. RESULTS: The HSA-SF interaction found to be a static
binding. The Stern-Volmer constants (Ksv) were in the range of ~104M-1 and other
thermodynamic parameters like enthalpy (DeltaH degrees ), free energy (DeltaG
degrees ) and entropy (DeltaS degrees ) are similar to albumin ligand bindings
reported by previous workers. CONCLUSIONS: The interactions were found to be
spontaneous, irrespective of temperature or glycation. Glycated HSA is clinically
used to monitor unstable glycemic controls in diabetic patients. A 39% increase
in binding affinity (log K) and free energy (DeltaG degrees ) is reported on
glycation at 310K (room temperature), which may be important in the SF based
angiographies. On glycation HSA-SF binding appears to change from an enthalpy
driven to an entropy-driven reaction. SF shows best binding to FA binding site
III of HSA, which also overlaps with drug binding site II of subdomain IIIA.
Leu430 seems to play a pivotal role in the interaction.
PMID- 28412198
TI - Potential role of lycopene in targeting proprotein convertase subtilisin/kexin
type-9 to combat hypercholesterolemia.
AB - Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of
the proprotien convertase (PC) family that has profound effects on plasma low
density lipoprotein cholesterol (LDL-C) levels, the major risk factor for
coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R)
protein degradation and reduced recycling to the surface of hepatocytes. Thus,
the current study was premeditated not only to evaluate the role of lycopene in
targeting the inhibition of PCSK-9 via modulation of genes involved in
cholesterol homeostasis in HFD rats but also to examine a correlation between HFD
induced inflammatory cascades and subsequent regulation of PCSK-9 expression.
Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for
PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular
informatics approach to assess the dual mode of action of lycopene in LDL-R
recycling and increased removal of circulatory LDL-C. We for the first time
deciphered that lycopene treatment significantly down-regulates the expression of
hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up
regulated. Furthermore, lycopene ameliorated inflammation stimulated expression
of PCSK-9 via suppressing the expression of inflammatory markers. The results
from our molecular informatics studies confirmed that lycopene, while occupying
the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to
complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex
formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A
complex. Based on above results, it can be concluded that lycopene exhibits
potent hypolipidemic activities via molecular mechanisms that are either
identical (HMGR inhibition) or distinct from that of statins (down-regulation of
PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report
that lycopene has this specific biological property. Being a natural, safer and
alternative therapeutic agent, lycopene could be used as a complete regulator of
cholesterol homeostasis and ASCVD.
PMID- 28412197
TI - An UPLC-MS/MS method for the quantification of BRAF inhibitors (vemurafenib,
dabrafenib) and MEK inhibitors (cobimetinib, trametinib, binimetinib) in human
plasma. Application to treated melanoma patients.
AB - Targeted therapies for cancers are fast-growing therapies. For instance kinase
inhibitors such as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are
increasingly used to treat malignant melanoma. The metabolic profile of these
drugs can result in great interindividual variability, justifying therapeutic
drug monitoring (TDM). We describe a rapid and specific method for quantification
of 2 BRAFi (vemurafenib, dabrafenib) and 3 MEKi (cobimetinib, trametinib and
binimetinib). Chromatography was performed on a Waters Acquity-UPLC system with
CORTECS C18+ column, under a gradient of 10% acetic acid in water/acetonitrile.
An Acquity-TQD(r) with electrospray ionization was used for detection. Samples
were prepared by solid phase extraction (Oasis(r) MCX microElution) before
injection in the system. Calibration curves ranges from 0.4 to 100MUg/ml for
vemurafenib, from 1 to 1000ng/ml for dabrafenib, from 0.5 to 500ng/ml for
cobimetinib and binimetinib, and from 0.75 to 250ng/ml for trametinib. At all
concentrations the bias was within +/-15% of the nominal concentrations and
precision was <=15%. All results were within the acceptance criteria of the EMA
guidelines on method validation. This rapid, sensitive and specific UPLC-MS/MS
method can perform simultaneous quantification of targeted therapies used in
malignant melanoma and is usable for routine TDM.
PMID- 28412199
TI - The AtrbohF-dependent regulation of ROS signaling is required for melatonin
induced salinity tolerance in Arabidopsis.
AB - Although several literatures confirmed the beneficial roles of exogenous
melatonin in the enhancement of salinity tolerance in plants, whether or how
endogenous melatonin confers plant salinity tolerance is still elusive. In the
report, we observed impaired melatonin level and salinity hypersensitivity in
atsnat, the Arabidopsis melatonin synthesis mutant. Above hypersensitivity was
rescued by melatonin or hydrogen peroxide. Meanwhile, melatonin-mediated salt
tolerance in wild-type was abolished by an NADPH oxidase inhibitor, suggesting
the possible role of NADPH oxidase-dependent reactive oxygen species (ROS).
Genetic evidence further showed that the rapid stimulated RbohF transcripts and
production of ROS elicited by melatonin in stressed wild-type plants were largely
abolished by the mutation of AtrbohF. Meanwhile, salinity sensitivity of atrbohF
mutant was not altered by melatonin, which was consistent with the higher Na+
content and the resulting greater Na+/K+ ratio, compared with those in wild-type
plants. Further changes of SOS1, SOS2, and SOS3 transcripts suggested that the
melatonin-triggered SOS-mediated Na+ efflux might be mediated by AtrbohF
dependent ROS. The addition of melatonin could intensify the increased
antioxidant defence in stressed wild-type but not in atrbohF mutant, both of
which were confirmed by the histochemical staining for ROS production and lipid
peroxidation during the later period of stress. Collectively, our genetic and
molecular evidence revealed that the AtrbohF-dependent ROS signaling is required
for melatonin-induced salinity tolerance via the reestablishment of ion and redox
homeostasis.
PMID- 28412200
TI - Three-year follow-up of children with abnormal newborn screening results for
congenital hypothyroidism.
AB - BACKGROUND: To analyze predictive factors suggesting transient congenital
hypothyroidism (TCH) compared to permanent congenital hypothyroidism (PCH) or
transient thyroid function test (TFT) abnormalities among children who had
positive screening results at our centers over the past decade. METHODS: A
retrospective chart review of 105 subjects who presented elevated TSH levels on a
newborn screening test (NST) was done. TCH was defined when a trial-off therapy
was successful, and PCH was defined when a trial failed or when the subject was
kept on medication beyond 3 years of age. A transient TFT abnormality was defined
when follow-up TFTs were normalized without levothyroxine (LT4) therapy. RESULTS:
Congenital hypothyroidism (CH) was diagnosed in 75.2% (TCH 35.2% and PCH 40.0%)
of all subjects; the others (24.8%) showed transient TFT abnormalities. Initial
NST-TSH levels (optimal cutoff point, 31.0 MUIU/mL), the LT4 dose at 2 years of
age (4.1 MUg/kg/day), and the maximal LT4 dose (50 MUg/day) merged as significant
predictive factors discriminating between TCH and PCH. The initial serum level of
free T4 (1.06 ng/dL) and not TSH (27.2 MUIU/mL) was the only discriminating
factor between transient TFT abnormalities and TCH. CONCLUSION: Earlier re
evaluation might be possible when a patient's initial NST-TSH levels and maximal
or 2-year LT4 doses are low, as both are important predictors of successful trial
off therapy in CH patients. When the initial serum level of free T4 is above the
average value in neonates with mildly elevated TSH levels, TFTs may be more
likely to normalize on their own.
PMID- 28412201
TI - Nitric oxide enhanced the growth of an obligated intracellular bacterium Orientia
tsutsugamushi in murine macrophages.
AB - Orientia tsutsugamushi is the causative agent of scrub typhus. It is an obligate
intracellular bacterium that grows only in eukaryotic cells. Macrophages play an
important role in innate immunity by surveilling the human body for pathogens. In
present study, it was demonstrated that O. tsutsugamushi propagated well in LPS
activated RAW 264.7 macrophages, but not in non-activated macrophages. In LPS
activated macrophages, the expression of Nos2, which encodes the inducible nitric
oxide (NO) synthase (iNOS), was highly upregulated compared to those in non
activated macrophages. Parallel to this upregulation, high NO production was
observed in LPS-activated macrophages. Transmissible electron microscopy showed
that O. tsutsugamushi replicated in the cytosol of macrophages. Thus, O.
tsutsugamushi was thought to escape the phagosomes at an early stage of phagosome
maturation to avoid the bactericidal effect of NO. Furthermore, O. tsutsugamushi
growth was enhanced in NO donor-supplied RAW 264.7 macrophages, as well as in LPS
activated, but not in non-activated macrophages. Consequently, these results
suggested that NO was rather essential for enhancing the replication of O.
tsutsugamushi in RAW 264.7 macrophages, despite the typically detrimental effects
of NO against intracellular pathogens. In the present study, NO was suggested to
activate specific pathways to enhance the growth of O. tsutsugamushi.
PMID- 28412202
TI - The immunosuppressive effects of a novel recombinant LipQ (Rv2485c) protein of
Mycobacterium tuberculosis on human macrophage cell lines.
AB - Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a
major global health challenge. A number of mycobacterial macromolecules have been
shown to target biological processes within host macrophages; however, the exact
mechanism for the majority of these host pathogen interactions is still poorly
understood. Moreover, the lipid metabolic pathway is one of the most important
physiologic pathways that plays a vital role in the survival and infection of
Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ
from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro.Our
results demonstrate that rLipQ significantly lowers the expression level of pro
inflammatory cytokines (TNF-alpha& IFN-gamma) and augments the level of anti
inflammatory cytokines such as IL-4 & IL-10as compared to LPS stimulated
macrophages. An up-regulation of anti-inflammatory and down-regulation of pro
inflammatory cytokines levels in rLipQ pretreated macrophages implies immuno
modulatory functions in TB patients. Interestingly, rLipQ also inhibited the
expression of iNOS, TLR-2 and transcription factor NF-kB in LPS stimulated
macrophages whereas the expression of TLR-4 remains unchanged. The inhibition in
the expression of these signaling molecules has been correlated to the inhibition
of NO production in macrophages. Taken together, these studies demonstrate that
rLipQ is a novel lipase that is highly immunogenic and may play an important role
in the virulence and pathogenesis of M. tuberculosis infection, by altering the
balance of cytokines, which might help to assess prognosis and contribute to a
better understanding against host-pathogen interactions.
PMID- 28412203
TI - ATP-sensitive inwardly rectifying potassium channel modulators alter cardiac
function in honey bees.
AB - ATP-sensitive inwardly rectifying potassium (KATP) channels couple cellular
metabolism to the membrane potential of the cell and play an important role in a
variety of tissue types, including the insect dorsal vessel, making them a
subject of interest not only for understanding invertebrate physiology, but also
as a potential target for novel insecticides. Most of what is known about these
ion channels is the result of work performed in mammalian systems, with insect
studies being limited to only a few species and physiological systems. The goal
of this study was to investigate the role that KATP channels play in regulating
cardiac function in a model social insect, the honey bee (Apis mellifera), by
examining the effects that modulators of these ion channels have on heart rate.
Heart rate decreased in a concentration-dependent manner, relative to controls,
with the application of the KATP channel antagonist tolbutamide and KATP channel
blockers barium and magnesium, whereas heart rate increased with the application
of a low concentration of the KATP channel agonist pinacidil, but decreased at
higher concentrations. Furthermore, pretreatment with barium magnified the
effects of tolbutamide treatment and eliminated the effects of pinacidil
treatment at select concentrations. The data presented here confirm a role for
KATP channels in the regulation of honey bee dorsal vessel contractions and
provide insight into the underlying physiology that governs the regulation of bee
cardiac function.
PMID- 28412204
TI - A calcineurin antifungal strategy with analogs of FK506.
AB - A novel antifungal strategy targeting the inhibition of calcineurin is described.
To develop a calcineurin based inhibitor of pathogenic fungi, analogs of FK506
were synthesized that were able to permeate mammalian but not fungal cells.
Antagonists in combination with FK506 were not immunosuppressive and retained
antifungal activity in A. fumigatus. To reduce the dosage burden of the
antagonist, murine oral PK was improved an order of magnitude relative to
previous FK506 antagonists.
PMID- 28412205
TI - SLC2A1/GLUT1 expression in mural nodules of intraductal papillary mucinous
neoplasm of the pancreas.
AB - In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural
nodule showing a papillary or nodular proliferation of tumor cells in the dilated
pancreatic duct is an indication for resection of IPMN. Solute carrier family 2,
facilitated glucose transporter member 1, known as glucose transporter type 1
(SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is
correlated with increased 18F-fluorodeoxyglucose (18F-FDG) uptake. We examined
SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish
malignant/benign tumors. A mural nodule was detected in 80 (44.4%) of the IPMNs,
and was detected in 18.6% (13/70) of the IPMN-low (dysplasia) specimens, 36.1%
(13/36) of the IPMN-int, 93.3% (28/30) of the IPMN-high, and 59.1% (26/44) of the
IPMN-inv (with an associated invasive carcinoma) specimens. The sensitivity for
detecting mural nodules was 81.7% by endoscopic ultrasonography, 70% by contrast
enhanced computed tomography and 54% by endoscopic retrograde
cholangiopancreatography. SLC2A1/GLUT1 expression in the mural nodules was
recognized in the basal and basolateral cytomembrane of tumor cells and was
expressed in 15.4% (2/13) of the IPMN-low, 15.4% (2/13) of the IPMN-int, 71.4%
(20/28) of the IPMN-high and 84.6% (22/26) of the IPMN-inv groups. The
SLC2A1/GLUT1 expression was significantly higher in the IPMN-high and IPMN-inv
mural nodules than in those of the IPMN-low and IPMN-int groups. Our findings
suggest that SLC2A1/GLUT1 is expressed late in the adenoma-carcinoma sequence
during carcinogenesis in IPMN, and SLC2A1/GLUT1 act as therapeutic target for
malignant IPMN.
PMID- 28412206
TI - Cicatricial variant of cryptogenic organizing pneumonia.
AB - This study of 12 patients focused on a variant of cryptogenic organizing
pneumonia (COP) labeled the cicatricial form in which the airspaces of the lung
are filled with and consolidated by dense collagenized scar tissue associated
with preservation of underlying lung architecture. Patients were predominantly
middle-aged men and presented with bilateral lung disease in the majority of
cases, often with nodular or reticulonodular disease (10/12; 83%). Patients were
usually symptomatic with shortness of breath, cough, and dyspnea on exertion.
Fifty-five percent of patients (6/11) had persistent or progressive disease at
follow-up (mean, 68.5 months; median, 110 months). The cicatricial variant of
cryptogenic organizing pneumonia may be predictive of a more recalcitrant form of
COP that needs to be morphologically separated from classical COP, usual
interstitial pneumonia, and nonspecific interstitial pneumonia.
PMID- 28412208
TI - High expression of P2X7R is an independent postoperative indicator of poor
prognosis in colorectal cancer.
AB - The purinergic P2X7 receptor (P2X7R) is a master regulator of inflammation and
inflammation-related diseases. Recently, P2X7R has been reportedly involved in
carcinogenesis and tumor progression. In this study, we investigated the
expression pattern and prognostic merit of P2X7R in human colorectal cancer
(CRC). The expression profile of P2X7R in 12 pairs of CRC and non-tumorous
specimens was evaluated using Western blotting analysis. Additionally, we
performed immunohistochemistry (IHC) on 116 paraffin-embedded CRC specimens, and
evaluated the correlation between P2X7R expression and clinicopathological
factors. P2X7R was overexpressed in CRC samples, compared with adjacent non
tumorous ones. High P2X7R expression significantly correlated with tumor size (P
= .0177), Lymph node metastasis (P = .0128), and TNM stage (P = .0081).
Furthermore, univariate and multivariate Cox regression analyses revealed that
P2X7R expression could serve as an independent prognostic factor for poor overall
survival (P = .0197). Treatment with P2X7R agonist BzATP led to the activation of
Akt and NF-kappaB pathways. Consequently, we revealed that BzATP accelerated the
proliferation of CRC cells, whereas co-incubation with PI3K/Akt inhibitor
LY294002 significantly impaired BzATP-induced proliferation of CRC cells. Our
findings implied that P2X7R may serve as a valuable prognostic indicator and
promising therapeutic target of CRC.
PMID- 28412207
TI - MicroRNA 183 family profiles in pheochromocytomas are related to clinical
parameters and SDHB expression.
AB - This study aims to examine the expression profiles of the miR-183 cluster (miR
96/182/183) in pheochromocytoma. Pheochromocytoma tissues were prospectively
collected from 50 patients with pheochromocytoma. Expression of miR-183 cluster
members and SDHB protein expression were analyzed in these tissues by
quantitative real-time polymerase chain reaction and immunohistochemistry,
respectively. The expression of miR-183 cluster members in pheochromocytomas was
correlated with the clinical and pathological parameters of these patients. The
expression levels of miR-183 cluster members were predominantly downregulated or
deleted in pheochromocytoma. Low expression or deletion of miR-96 was
predominantly noted in younger patients with pheochromocytoma (<50 years, P=.01).
Female patients in the study group showed marked deletion of miR-182 (P=.05).
Deletion of the cluster was also associated with SDHB protein expression in
pheochromocytoma. Moreover, patients with low miR-183 cluster expression had a
slightly better survival rate when compared with patients with high expression.
To conclude, the findings indicate a role for miR-183 cluster members in the
pathogenesis and clinical progression of pheochromocytoma.
PMID- 28412209
TI - Mortalin expression in pancreatic cancer and its clinical and prognostic
significance.
AB - Mortalin, an essential mitochondrial chaperone protein, is involved in the
tumorigenesis of a number of malignancies. This study aimed to investigate the
expression of Mortalin in pancreatic ductal adenocarcinoma (PDAC) cells and to
determine its clinicopathological and prognostic significance. The localization
of Mortalin protein was detected in BXPC-3 PDAC cells using immunofluorescence.
Immunohistochemistry was also used to detect Mortalin expression in well-defined
tissues obtained from 106 PDAC patients and 46 corresponding nontumor pancreatic
tissues. Clinicopathological parameters and overall survival data were collected
and compared between different Mortalin statuses. The results of
immunohistochemistry and immunofluorescence showed that Mortalin was primarily
present in the cytoplasm of PDAC cells. The ratio of strong positive staining for
Mortalin was higher in PDAC tissues (55.66%; 59/106) than in normal adjacent
tissues (23.91%; 11/46). Positive relationships between Mortalin expression and
clinical stage, perineural invasion, lymph node metastasis, and lower overall
survival were observed. Multivariate Cox regression analysis identified Mortalin
as a significant independent prognostic factor, in addition to location, clinical
stage, and perineural invasion, for survival of PDAC patients. Therefore, we
present strong evidence that Mortalin may function as a practical marker to
predict prognosis and as a potential therapeutic target in PDAC treatment.
PMID- 28412210
TI - IMP3 expression in biopsy specimens as a diagnostic biomarker for colorectal
cancer.
AB - No single biological marker is used in routine diagnosis of colorectal cancer
(CRC) in endoscopic biopsies. IMP3 is a good independent prognostic biomarker for
CRC. However, the expression of IMP3 in hyperplastic polyp (HP) and adenoma has
not yet been studied. Moreover, no studies have established the diagnostic value
of IMP3 in biopsies. This study aims to assess IMP3 expression in HP, adenoma,
and CRC in resection specimens and to investigate its value in diagnosis of CRC
in biopsies. A total of 1328 specimens (633 of polypectomy, 395 surgical
resections, 300 biopsies) were retrospectively analyzed. IMP3 expression was
observed in 0 of 197 (0%) normal tissues, 0 of 130 (0%) HPs, 14 of 504 (2.8%)
adenomas, and 139 of 197 (70.6%) CRCs. IMP3 was found to be overexpressed in CRC
compared with adenoma (P<.001). Among the 300 biopsies, 56 were diagnosed as
adenoma, and 244 were CRCs. Of the 56 adenoma cases, 22 (39.3%) were confirmed,
whereas 34 (60.7%) were diagnosed as CRC in resection specimens. All 244 CRC
biopsies were confirmed by resection specimens. IMP3-positive expression was
observed in 204 of 300 (68.0%) biopsies, including in 22 of 56 (39.3%) adenomas
and 182 of 244 (74.6%) CRCs. All IMP3-positive expressions in the biopsies were
finally diagnosed as CRC. Our findings demonstrated that IMP3 is a reliable
marker for the diagnosis of CRC in endoscopic biopsies.
PMID- 28412211
TI - Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response
and prognosis in stage II/III breast cancer.
AB - The predictive value of serum miRNAs (ser-miRNA) for the response to neoadjuvant
chemotherapy (NCT) and the prognosis of breast cancer patients were investigated
in the current study. The study included 118 stage II/III breast cancer patients
and 30 healthy adult women. Peripheral blood was drawn from participants before
the start (baseline [BL]), at the end of the second cycle (first evaluation
during NCT [FEN]), and at the end of NCT (second evaluation during NCT [SEN]).
The expression of ser-miRNAs was examined by quantitative reverse-transcription
polymerase chain reaction (qRT-PCR), and their association with chemotherapy
response and prognosis was analyzed. MiR-19a, miR-21, miR-125b, miR-155, miR-205,
and miR-373 were significantly up-regulated in the serum of breast cancer
patients at BL, miR-451 was significantly down-regulated, and miR-122 was
unchanged compared with the levels in healthy women. The expression of ser-miR
125b and the changes of ser-miR-21 expression during NCT were associated with
chemotherapy response and disease-free survival (DFS). In chemotherapy
responders, ser-miR-125b expression was lower than that of non-responders at BL,
FEN, and SEN, and ser-miR-21 levels decreased from BL to FEN and from BL to SEN.
Survival analysis showed that patients with lower ser-miR-125b expression at BL,
FEN, and SEN had favorable DFS, and those with decreased ser-miR-21 expression
from BL to FEN and from BL to SEN had better DFS. In conclusion, ser-miR-21 and
ser-miR-125b were identified as novel, noninvasive predictive markers for NCT
response and prognosis in breast cancer.
PMID- 28412212
TI - Mucoepidermoid carcinoma with extensive spindled morphology and melanocytic
marker expression.
AB - Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the
salivary gland. Albeit common, histologic variants have rarely been noted in MEC.
Here, we report a 49-year-old man with a sublingual gland tumor. Histologically,
the tumor was composed of spindle cells arranged in interlacing fascicules or
globular nests. A few bland small glands containing mucous cells were also
scattered. The spindle tumor cells completely lacked immunoreactivity for
cytokeratin, and exhibited immunoreactivity for vimentin, S-100, HMB-45, Melan A,
and SOX10. The tumor was initially suspected to be clear cell sarcoma, malignant
melanoma, or perivascular epithelioid cell tumor with a few entrapped
nonneoplastic duct epitheliums. However, reverse-transcription polymerase chain
reaction revealed the CRTC3-MAML2 fusion gene product diagnostic of MEC. In fact,
a very minor component of the epithelial cells was reminiscent of conventional
MEC, whereas major spindled tumor cells possessed markedly altered
differentiation. This is the first case report of MEC with extensive spindled
morphology and melanocytic marker expression.
PMID- 28412213
TI - Acute mast cell leukemia associated with t(4;5)(q21;q33).
AB - To the best of our knowledge, this manuscript describes clinical and pathologic
findings of the first case of acute mast cell leukemia harboring t(4;5)(q21;q33),
compatible with fusion of the PDGFRB gene to a rare partner, PRKG2. Translocation
involving the PDGFRB gene is confirmed by fluorescence in situ hybridization
study. This case presented a relatively fulminant clinical course with acute mast
cell leukemia and "C" findings (cytopenia, hepatosplenomegaly, and weight loss),
mast cell sarcoma, and severe basophilia. Despite aggressive presentation
initially, the patient responded well to tyrosine kinase inhibitor treatment and
is currently in complete remission 33 months after diagnosis. This case
significantly extends the disease spectrum associated with PRKG2/PDGFRB fusion
gene. Recognizing the whole spectrum of diseases associated with this fusion is
critical because tyrosine kinase inhibitor treatment has been exceedingly
effective in these patients.
PMID- 28412214
TI - Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of
non-small cell lung cancer via inhibition of transforming growth factor beta1
signaling pathway in vitro and in vivo.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Bu-Fei decoction
(BFD) has been utilized to treat patients with Qi deficiency for decades, with
the advantages of invigorating vital energy, clearing heat-toxin and moistening
lung, etc. According to previous clinical experience and trials, BFD has been
found to indeed improve life quality of lung cancer patients and prolong survival
time. Nevertheless, little is known on its potential mechanisms so far. Being
regarded as a pivotal cytokine in the tumor microenvironment, transforming growth
factor beta (TGF-beta) stands out as a robust regulator of epithelial-mesenchymal
transition (EMT), which is closely linked to tumor progression. AIM OF THE STUDY:
The present study was designed to explore whether BFD antagonized EMT via
blocking TGF-beta1-induced signaling pathway, and then help contribute to create
a relatively steady microenvironment for confining lung cancer. MATERIALS AND
METHODS: This experiment was performed in lung adenocarcinoma A549 cells both in
vitro and in vivo. In detail, the influences mediated by TGF-beta1 alone or in
combination with different concentrations of BFD on migration were detected by
wound healing and transwell assays, and the effects of BFD on cell viability were
determined by cell counting kit-8 (CCK-8) assay. TGF-beta1, EMT relevant proteins
and genes were evaluated by western blotting, confocal microscopy, quantitative
real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and
enzyme-linked immuno sorbent assay (ELISA). Female BALB/C nude mice were
subcutaneously implanted A549 cells and given BFD by gavage twice daily for 28
days. The tumor volume was monitored every 4 days to draw growth curve. The tumor
weight, expression levels of EMT-related protein in tumor tissues and TGF-beta1
serum level were evaluated, respectively. RESULTS: BFD only exerted minor effects
on A549 cell proliferation and this was in accordance with the in vivo result,
which showed that the tumor growth and weight were not be restrained by BFD
administration. However, the data elucidated that BFD could dose-dependently
suppress EMT induced by TGF-beta1 in vitro via attenuating canonical Smad
signaling pathway. In the A549 xenograft mouse model, BFD also inhibited protein
markers that are associated with EMT and TGF-beta1 secretion into serum.
CONCLUSIONS: Based on these above data, the conclusion could be put forward that
BFD probably attenuated TGF-beta1 mediated EMT in A549 cells via decreasing
canonical Smad signaling pathway both in vitro and in vivo, which may help
restrain the malignant phenotype induced by TGF-beta1 in A549 cells to some
extent.
PMID- 28412215
TI - Involvement of serotonergic, noradrenergic and dopaminergic systems in the
antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax
ginseng C.A. Meyer.
AB - ETHNOPHARMACOLOGY RELEVANCE: Ginsenoside Rb1, a 20 (S)-protopanaxadiol, is a
major active ingredient of Panax ginseng C.A. Meyer, which as the King of Chinese
herbs, has been wildly used for the treatment of central nervous system diseases.
Previous studies have shown that 20 (S)-protopanaxadiol possesses a novel
antidepressant-like effect in the treatment of depression, whereas ginsenoside
Rb1 in depression has been rarely reported. AIM OF THE REVIEW: The present study
was to investigate the antidepressant-like effect of ginsenoside Rb1 and its
relevant mechanisms. MATERIALS AND METHODS: The whole experiment was divided into
two parts: one part we examined the antidepressant-like effect of ginsenoside Rb1
with open-field test (OFT), tail suspension test (TST), forced swim test (FST), 5
HTP induced head-twitch and reserpine response in mice, another part we used
chronic unpredicted mild stress (CUMS) model to further explore the
antidepressant-like effect of ginsenoside Rb1 with caffeine, fluoxetine and p
Chlorophenylalanine (PCPA) in rats. Furthermore, the levels of monoamine
neurotransmitters of NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, HVA were
all measured by ELISA kits after the CUMS protocol. RESULTS: Our data indicated
that 7 days treatment with ginsenoside Rb1 (4, 8, 10mg/kg, p.o.) significantly
decreased immobility time in the FST and TST in mice, and played important roles
in mice which were induced by 5-HTP (200mg/kg, i.p.) and reserpine (4mg/kg,
i.p.). On the basis of CUMS model, 21 days treatment with ginsenoside Rb1 not
only had effective interactions with caffeine (5mg/kg, i.p.), fluoxetine (1mg/kg,
i.p.) and PCPA (100mg/kg, i.p.), but also significantly up-regulated the 5-HT, 5
HIAA, NE and DA levels in CUMS rats' brain, whereas HVA and DOPAC had no
significant difference. Moreover, there was no alteration in spontaneous
locomotion in any experimental group. CONCLUSIONS: These results suggest that
ginsenoside Rb1 exhibits significant antidepressant-like effect in behavioral
tests, chronic animal model and drug interactions, its mechanisms mainly mediated
by central neurotransmitters of serotonergic, noradrenergic and dopaminergic
systems.
PMID- 28412216
TI - Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post
ischemic pain by activation of pro-resolving pathways.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris Sw. is widely used in popular
medicine to treat conditions associated with pain. AIM OF THE STUDY: The present
study investigated the influence of hydroalcoholic crude extract of Casearia
sylvestris (HCE-CS) and contribution of pro-resolving mediators on mechanical
hyperalgesia in a mouse model of chronic post-ischemia pain (CPIP). METHODS AND
RESULTS: Male Swiss mice were subjected to ischemia of the right hind paw (3h),
then reperfusion was allowed. At 10min, 24h or 48h post-ischemia/reperfusion
(I/R), different groups of animals were treated with HCE-CS (30mg/Kg, orally
[p.o]), selected agonists at the pro-resolving receptor ALX/FPR2 (natural
molecules like resolvin D1 and lipoxin A4 or the synthetic compound BML-111; 0.1
1ug/animal) or vehicle (saline, 10mL/Kg, s.c.), in the absence or presence of the
antagonist WRW4 (10ug, s.c.). Mechanical hyperalgesia (paw withdrawal to von Frey
filament) was asseseed together with histological and immunostainning analyses.
In these settings, pro-resolving mediators reduced mechanical hyperalgesia and
HCE-CS or BML-111 displayed anti-hyperalgesic effects which was markedly
attenuated in animals treated with WRW4. ALX/FPR2 expression was raised in
skeletal muscle or neutrophils after treatment with HCE-CS or BML-111.
CONCLUSION: These results reveal significant antihyperalgesic effect of HCE-CS on
CPIP, mediated at least in part, by the pathway of resolution of inflammation
centred on the axis modulated by ALX/FPR2.
PMID- 28412217
TI - Dalbergia odorifera extract promotes angiogenesis through upregulation of VEGFRs
and PI3K/MAPK signaling pathways.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: The heart wood of Dalbergia odorifera is a
Chinese herbal medicine commonly used for the treatment of various ischemic
diseases in Chinese medicine practice. AIM OF THE STUDY: In this study,
therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were
investigated on transgenic zebrafish in vivo and human umbilical vein endothelial
cells (HUVECs) in vitro. MATERIALS AND METHODS: The pro-angiogenic effects of DOE
on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and
intersegmental vessels (ISVs) injury assay. And the pro-angiogenic effects of DOE
on HUVECs were examined by MTT, scratch assay, protein chip and western blot.
RESULTS: In the in vivo studies, we found that DOE was able to dose-dependently
promote angiogenesis in zebrafish SIVs area. In addition, DOE could also restore
the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of
VEGFRs including kdr, kdrl and flt-1 induced by VEGF receptor kinase inhibitor II
(VRI). In the in vitro studies, we observed that DOE promoted the proliferation,
migration of HUVECs and also restored the injury induced by VRI. Moreover,
protein chip and western blot experiments showed the PI3K/MAPK cell
proliferation/migration pathway were activated by DOE. CONCLUSIONS: DOE has a
therapeutic effects on angiogenesis, and its mechanism may be related to
adjusting the VEGFRs mRNA and activation of PI3K/MAPK signaling pathway. These
results suggest a strong potential for Dalbergia odorifera to be developed as an
angiogenesis-promoting therapeutic.
PMID- 28412218
TI - Evaluation of the combined use of metronomic zoledronic acid and Coriolus
versicolor in intratibial breast cancer mouse model.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Coriolus versicolor (CV) is a mushroom
traditionally used for strengthening the immune system and nowadays used as
immunomodulatory adjuvant in anticancer therapy. Breast cancer usually
metastasizes to the skeleton, interrupts the normal bone remodeling process and
causes osteolytic bone lesions. The aims of the present study were to evaluate
its herb-drug interaction with metronomic zoledronate in preventing cancer
propagation, metastasis and bone destruction. MATERIALS AND METHODS: Mice
inoculated with human breast cancer cells tagged with a luciferase (MDA-MB-231
TXSA) in tibia were treated with CV aqueous extract, mZOL, or the combination of
both for 4 weeks. Alteration of the luciferase signals in tibia, liver and lung
were quantified using the IVIS imaging system. The skeletal response was
evaluated using micro-computed tomography (micro-CT). In vitro experiments were
carried out to confirm the in vivo findings. RESULTS: Results showed that
combination of CV and mZOL diminished tumor growth without increasing the
incidence of lung and liver metastasis in intratibial breast tumor model. The
combination therapy also reserved the integrity of bones. In vitro studies
demonstrated that combined use of CV and mZOL inhibited cancer cell proliferation
and osteoclastogenesis. CONCLUSIONS: These findings suggested that combination
treatment of CV and mZOL attenuated breast tumor propagation, protected against
osteolytic bone lesion without significant metastases. This study provides
scientific evidences on the beneficial outcome of using CV together with mZOL in
the management of breast cancer and metastasis, which may lead to the development
of CV as adjuvant health supplement for the control of breast cancer.
PMID- 28412219
TI - Medicinal plant uses and names from the herbarium of Francesc Bolos (1773-1844).
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotany takes into account past uses to be
projected into the present and future. Most current ethnobotanical research is
focused, especially in industrialised countries, on obtaining information of
plant uses from elderly people. Historical ethnobotany is less cultivated,
although papers have demonstrated its interest. Particularly poor, but
potentially very relevant, is the attention paid to historical herbaria as a
source of data on useful plants. AIMS OF THE STUDY: Bearing this in mind, we
studied the herbarium of the Catalan pharmacist and naturalist Francesc Bolos
(1773-1844), which contains information on medicinal uses and folk names, with
the aim of establishing a catalogue of plants and uses and tracing them through
old and contemporary literature. METHODOLOGY: The ca. 6000 plant specimens of
this herbarium were investigated to assess those including plant uses and names.
These taxa have been thoroughly revised. The data have been tabulated, their
biogeographic profile, possible endemic or threatened status, or invasive
behaviour have been assessed, and the content regarding medicinal uses, as well
as folk names, has been studied. The medicinal terms used have been interpreted
as per current days' medicine. The popular names and uses have been compared with
those appearing in a certain number of works published from 11th to 20th
centuries in the territories covered by the herbarium and with all the data
collected in 20th and 21st centuries in an extensive database on Catalan
ethnobotany. RESULTS: A total of 385 plant specimens (381 taxa) have been
detected bearing medicinal use and folk names information. We collected data on
1107 reports of plant medicinal properties (in Latin), 32 indications of
toxicity, nine reports of food use, and 123, 302 and 318 popular plant names in
Catalan, Spanish and French, respectively. The most quoted systems are digestive,
skin and subcutaneous tissue (plus traumatic troubles) and genitourinary.
Relatively high degrees of coincidence of plant names and uses in the herbarium
and the literature comparison set have been found. Of the taxa contained in this
medicinal herbarium, 294 were native to the Iberian Peninsula, and 86 were alien.
Neither endemic nor threatened taxa have been detected, whereas a considerable
portion of the alien taxa shows invasive behaviour at present. CONCLUSIONS: Our
analyses indicate a certain degree of consistency between the medicinal uses of
plants recorded in this 18th and 19th century herbarium and the records found in
the literature and in recent ethnobotanical datasets, accounting for the
robustness of pharmaceutical ethnobotanical knowledge in the area considered.
Data appearing on the specimen labels are numerous, pointing out the herbarium as
a relevant source of ethnopharmacological information. Special attention should
be paid to some original uses contained in the herbarium's labels for further
investigation on plant properties and drug design.
PMID- 28412221
TI - Opportunities for women in sport in Brazil: Expectations after Rio 2016.
PMID- 28412220
TI - Inflammation-induced GluA1 trafficking and membrane insertion of Ca2+ permeable
AMPA receptors in dorsal horn neurons is dependent on spinal tumor necrosis
factor, PI3 kinase and protein kinase A.
AB - Peripheral inflammation induces sensitization of nociceptive spinal cord neurons.
Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca2+
permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant
pain behavior, molecular mechanisms connecting these two events have not been
studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw
carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and
GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected
rats compared to controls. In the same tissue, GluA2 levels were not altered.
Inflammation-induced increases in membrane GluA1 were prevented by i.t. pre
treatment with antagonists to TNF, PI3K, PKA and NMDA. Interestingly,
administration of TNF or PI3K inhibitors followed by carrageenan caused a marked
reduction in plasma membrane GluA2 levels, despite the fact that membrane GluA2
levels were stable following inhibitor administration in the absence of
carrageenan. TNF pre-incubation induced increased numbers of Co2+ labeled dorsal
horn neurons, indicating more neurons with Ca2+ permeable AMPAr. In parallel to
Western blot results, this increase was blocked by antagonism of PI3K and PKA. In
addition, spinal slices from GluA1 transgenic mice, which had a single alanine
replacement at GluA1 ser 845 or ser 831 that prevented phosphorylation, were
resistant to TNF-induced increases in Co2+ labeling. However, behavioral
responses following intraplantar carrageenan and formalin in the mutant mice were
no different from littermate controls, suggesting a more complex regulation of
nociception. Co-localization of GluA1, GluA2 and GluA4 with synaptophysin on
identified spinoparabrachial neurons and their relative ratios were used to
assess inflammation-induced trafficking of AMPAr to synapses. Inflammation
induced an increase in synaptic GluA1, but not GluA2. Although total GluA4 also
increased with inflammation, co-localization of GluA4 with synaptophysin, fell
short of significance. Taken together these data suggest that peripheral
inflammation induces a PI3K and PKA dependent TNFR1 activated pathway that
culminates with trafficking of calcium permeable AMPAr into synapses of
nociceptive dorsal horn projection neurons.
PMID- 28412223
TI - Bioengineered robust hybrid hydrogels enrich the stability and efficacy of
biological drugs.
AB - Biological drugs are exquisitely tailored components offering the advantages of
high specificity and efficacy that are considered safe for treating diseases.
Nevertheless, the effectiveness of biological drugs is limited by their inherent
short biological half-life and poor stability in vivo. Herein, we engineered a
novel delivery platform based on hybrid injectable hydrogels, in which pH- and
temperature-responsive biodegradable copolymers were site-specifically coupled to
the sulfhydryl group of human serum albumin, which effectively enhances the
stability and circulation half-life of the biological drug, recombinant uricase
enzyme (Uox). The albumin ligand conjugated to the Uox allowed specific-binding
of the enzyme within the protein shell, and the synthetic polymers effectively
shield the protein-enzyme complex. Such close confinement exhibits strong
resistance towards various physical, chemical and therapeutically relevant
stressors such as temperature, pH and proteases. Subcutaneous administration of
Uox-loaded bioengineered hybrid hydrogel improved the pharmacokinetics by
prolonging its circulation half-life. As a consequence, the bioengineered hybrid
hydrogel normalized the serum uric acid level in hypoxanthine/potassium oxonate
induced hyperuricemia mice, and no obvious side effects were observed in the
major organs. The characteristic of the bioengineered hydrogel networks
applicable to a variety of biological drugs by simple mixing that unlock the
possibility of adapting biological drugs to therapeutic applications.
PMID- 28412222
TI - Targeted drug distribution in tumor extracellular fluid of GD2-expressing
neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles
conjugated to the monoclonal antibody 3F8.
AB - Neuroblastoma is a pediatric solid tumor with high expression of the tumor
associated antigen disialoganglioside GD2. Despite initial response to induction
therapy, nearly 50% of high-risk neuroblastomas recur because of chemoresistance.
Here we encapsulated the topoisomerase-I inhibitor SN-38 in polymeric
nanoparticles (NPs) surface-decorated with the anti-GD2 mouse mAb 3F8 at a mean
density of seven antibody molecules per NP. The accumulation of drug-loaded NPs
targeted with 3F8 versus with control antibody was monitored by microdialysis in
patient-derived GD2-expressing neuroblastoma xenografts. We showed that the
extent of tumor penetration by SN-38 was significantly higher in mice receiving
the targeted nano-drug delivery system when compared to non-targeted system or
free drug. This selective penetration of the tumor extracellular fluid translated
into a strong anti-tumor effect prolonging survival of mice bearing GD2-high
neuroblastomas in vivo.
PMID- 28412224
TI - Mechanism-based selection of stabilization strategy for amorphous formulations:
Insights into crystallization pathways.
AB - We developed a step-by-step experimental protocol using differential scanning
calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy
(PLM) and a small-scale dissolution apparatus (MUDISS Profiler) to investigate
the mechanism (solid-to-solid or solution-mediated) by which crystallization of
amorphous drugs occurs upon dissolution. This protocol then guided how to
stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and
glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as
stabilizing polymers. Spray-dried amorphous indapamide, metolazone and
glibenclamide crystallized via solution-mediated nucleation while glipizide
suffered from solid-to-solid crystallization. The addition of 0.001%-0.01% (w/v)
HPMC into the dissolution medium successfully prevented the crystallization of
supersaturated solutions of indapamide and metolazone whereas it only reduced the
crystallization rate for glibenclamide. Amorphous solid dispersion (ASD)
formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did
not completely eliminate the solid-to-solid crystallization of glipizide even
though the overall dissolution rate was enhanced both in the absence and presence
of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in
the dissolution medium with higher solubility than the stable polymorph. As a
complementary technique, molecular dynamics (MD) simulations of indapamide and
glibenclamide with HPMC was performed. It was revealed that hydrogen bonding
patterns of the two drugs with HPMC differed significantly, suggesting that
hydrogen bonding may play a role in the greater stabilizing effect on
supersaturation of indapamide, compared to glibenclamide.
PMID- 28412226
TI - Expression profiling-based clustering of healthy subjects recapitulates
classifications defined by clinical observation in Chinese medicine.
AB - Differences between healthy subjects and associated disease risks are of
substantial interest in clinical medicine. Based on clinical presentations,
Traditional Chinese Medicine (TCM) classifies healthy people into nine
constitutions: Balanced, Qi, Yang or Yin deficiency, Phlegm-dampness, Damp-heat,
Blood stasis, Qi stagnation, and Inherited special constitutions. In particular,
Yang and Yin deficiency constitutions exhibit cold and heat aversion,
respectively. However, the intrinsic molecular characteristics of unbalanced
phenotypes remain unclear. To determine whether gene expression-based clustering
can recapitulate TCM-based classification, peripheral blood mononuclear cells
(PBMCs) were collected from Chinese Han individuals with Yang/Yin deficiency (n =
12 each) and Balanced (n = 8) constitutions, and global gene expression profiles
were determined using the Affymetrix HG-U133A Plus 2.0 array. Notably, we found
that gene expression-based classifications reflected distinct TCM-based subtypes.
Consistent with the clinical observation that subjects with Yang deficiency tend
toward obesity, series-clustering analysis detected several key lipid metabolic
genes (diacylglycerol acyltransferase (DGAT2), acyl-CoA synthetase (ACSL1), and
ATP-binding cassette subfamily A member 1 (ABCA1)) to be down- and up-regulated
in Yin and Yang deficiency constitutions, respectively. Our findings suggest that
Yin/Yang deficiency and Balanced constitutions are unique entities in their mRNA
expression profiles. Moreover, the distinct physical and clinical characteristics
of each unbalanced constitution can be explained, in part, by specific gene
expression signatures.
PMID- 28412227
TI - Generation of thermosensitive male-sterile maize by targeted knockout of the
ZmTMS5 gene.
PMID- 28412225
TI - Enhancing tissue permeability with MRI guided preclinical focused ultrasound
system in rabbit muscle: From normal tissue to VX2 tumor.
AB - High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing
physical energy based modality to ablate solid tumors with high power, or
increase local permeability in tissues/tumors in pulsed mode with relatively low
power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU
(pHIFU) is present in the majority of novel applications recently developed for
enhancing the delivery of drugs and genes. Previous studies have demonstrated the
capability of pHIFU to change tissue local permeability for enhanced drug
delivery in both mouse tumors and mouse muscle. Further study based on bulk
tissues in large animals and clinical HIFU system revealed correlation between
therapeutic effect and thermal parameters, which was absent in the previous mouse
studies. In this study, we further investigated the relation between the
therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues
based on a rabbit model and a preclinical HIFU system. Correlation between
therapeutic effect and thermal parameters was confirmed in our study on the same
bulk tissues although different HIFU systems were used. Following the study in
bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors
implanted on both hind limbs of rabbits and investigated the feasibility to
enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU
technique. A radiolabeled peptidomimetic integrin antagonist, 111In-DOTA-IA, was
used following pHIFU treatment in our study to target VX2 tumor and serve as the
radiotracer for follow-up single-photon emission computed tomography (SPECT)
scanning. The results have shown significantly elevated uptake of 111In-DOTA-IA
in the area of VX2 tumors pretreated by pHIFU compared with the control VX2
tumors not being pretreated by pHIFU, and statistical analysis revealed averaged
34.5% enhancement 24h after systematic delivery of 111In-DOTA-IA in VX2 tumors
pretreated by pHIFU compared with the control VX2 tumors.
PMID- 28412228
TI - Temperature effect on CRISPR-Cas9 mediated genome editing.
AB - Zinc-finger nuclease (ZFN), transcription activator-like effector nuclease
(TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR
associated protein 9 (CRISPR-Cas9) are the most commonly used genome editing
tools. Previous studies demonstrated that hypothermia treatment increased the
mutation rates induced by ZFNs and TALENs in mammalian cells. Here, we
characterize the effect of different culture temperatures on CRISPR-Cas9 mediated
genome editing and find that the genome editing efficiency of CRISPR-Cas9 is
significantly hampered by hypothermia treatment, unlike ZFN and TALEN. In
addition, hyperthermia culture condition enhances genome editing by CRISPR-Cas9
in some cell lines, due to the higher enzyme activity and sgRNA expression level
at higher temperature. Our study has implications on CRISPR-Cas9 applications in
a broad spectrum of species, many of which do not live at 37 degrees C.
PMID- 28412231
TI - Prenatal imaging presentation of Meckel diverticulum.
PMID- 28412232
TI - Accuracy of video observation and a three-dimensional head tracking system for
detecting and quantifying robot-simulated head movements in cone beam computed
tomography.
AB - OBJECTIVES: To assess the accuracy of detecting robot-simulated head movements
using video observation (VO) and 3-dimensional head tracking (HT) in a cone beam
computed tomography examination setup. STUDY DESIGN: A mannequin head was mounted
on a robot that was programmed to simulate patient head movements. Six types of
movement (tremor, nodding, lateral rotation, lifting, swallowing, and
anteroposterior translation), 3 distances (0.25, 1, and 5 mm), and 2 speeds (1
and 5 mm/s) were tested in triplicate (108 examinations). An additional 18 videos
and HT of no-motion served as controls for a total of 126 examinations. Three
blinded observers viewed video recordings of the examinations, scoring whether
the head moved and the movement type. HT provided quantitative measures of
movement distance. Accuracy, sensitivity, and specificity for movement detection
by VO and HT were calculated, related to true type, distance, and speed of
movement. Differences between the true and the measured movement distances were
assessed for HT. RESULTS: VO movement detection presented accuracy of 0.86,
sensitivity of 0.85, and specificity of 0.94. Anteroposterior translation (33.3%)
and 0.25 mm movements (41.7%) were often not detected by VO. HT correctly
detected all cases (accuracy = 1). HT presented small differences between the
true and the measured movement distances (average 20-54 MUm). CONCLUSIONS: VO
missed 41.7% of the 0.25 mm movements. HT correctly detected all movements and
quantified movements with an average error <55 MUm.
PMID- 28412229
TI - Characteristics and Factors Associated With Pain in Older Homeless Individuals:
Results From the Health Outcomes in People Experiencing Homelessness in Older
Middle Age (HOPE HOME) Study.
AB - : Individuals experiencing homelessness in the United States are aging; little is
known about chronic pain in this population. In a cross-sectional, population
based study, we interviewed 350 homeless individuals aged 50 years and older to
describe pain experienced by older persons experiencing homelessness and to
assess factors associated with chronic moderate to severe pain, defined as pain
lasting >=3 months, with a past week average severity score of 5 to 10 (scale 0
10). The median age of participants was 58 years. Participants were predominantly
African American (79.6%) and male (77.3%). Overall, 46.8% reported chronic
moderate to severe pain. Almost half of participants reported a diagnosis of
arthritis (44.3%) and one-third reported symptoms consistent with post-traumatic
stress disorder (PTSD; 32.8%). Three-quarters (75.3%) endorsed a personal history
of abuse. In multivariate analyses, PTSD (adjusted odds ratio [AOR]: 2.2, 95%
confidence interval [CI], 1.4-3.7), arthritis (AOR: 4.8, 95% CI, 3.0-7.8), and
history of experiencing abuse (AOR: 2.4, 95% CI, 1.3-4.3) were associated with
chronic moderate to severe pain. HIV status, diabetes, depressive symptoms, and
substance use were not associated with pain. Clinicians should consider the
management of associated mental health conditions and the sequelae of
experiencing abuse in the treatment of chronic pain in older adults experiencing
homelessness. PERSPECTIVE: This article describes the prevalence and factors
associated with chronic pain in older homeless adults. Almost half report chronic
pain, which was associated with PTSD, arthritis, and personal history of abuse.
Clinicians should address chronic pain, trauma, and the associated mental health
conditions in this high-risk population.
PMID- 28412230
TI - Oral health 4 life: Design and methods of a semi-pragmatic randomized trial to
promote oral health care and smoking abstinence among tobacco quitline callers.
AB - Smokers are at high risk for oral disease. As a result, they represent an
important target group for population-level, public oral health promotion
efforts. While dental health professionals often address smoking with their
patients, no systematic efforts have been made to offer smokers an intervention
to improve their use of oral health care. This paper details the rationale,
design, and methods of a large, semi-pragmatic, randomized clinical trial
designed to address this gap. Participants are recruited via the Oregon, Nebraska
and Louisiana state-sponsored tobacco quitlines and randomized to receive
standard quitline care versus standard care plus a multi-modal oral health
promotion program (Oral Health 4 Life) integrated within the quitline services.
All participants are followed for 6months to assess the impact of the
intervention on smoking abstinence and utilization of professional dental care.
In addition, the study will assess the cost of the intervention and provide
practical guidance to states on whether the intervention is financially feasible
to implement, should the intervention be effective. This study protocol may be
useful to others interested in promoting oral health among smokers, those
interested in partnering with tobacco quitlines to extend standard services to
address other high risk health behaviors among smokers, or those interested in
semi-pragmatic trial design.
PMID- 28412233
TI - Importance of tumor extent in adenosquamous carcinoma of the head and neck: a
retrospective cohort study.
AB - OBJECTIVE: The aim of this study was to determine the correlates of survival for
patients diagnosed with adenosquamous carcinoma (ASC) of the head and neck. STUDY
DESIGN: Patients diagnosed with ASC of the head and neck between 1973 and 2012
were identified from the Surveillance, Epidemiology, and End Results (SEER)
database. Kaplan-Meier and Cox proportional hazard regression analyses were
conducted to investigate the prognostic factors and treatment modalities that
determine overall survival (OS) and disease-specific survival (DSS). RESULTS: In
the analysis, of the 235 patients diagnosed with adenosquamous of the head and
neck, 66.8% were male and 33.2% were female with a median age at diagnosis of 64
years. Kaplan-Meier analysis determined 5-year survival rates of 30% for OS and
50% for DSS. Univariate and multivariate analyses found that age at diagnosis,
tumor size, tumor extent of disease, surgical resection, and radiation therapy
were independent predictors of OS and DSS. CONCLUSIONS: This study, to our
knowledge, is the largest study, to date, determining the correlates of survival
for ASC of the head and neck. Older age at diagnosis, larger tumor size, and
further extent of disease were correlated with decreased survival. Surgical
resection improves survival in patients with localized or regional disease,
whereas radiation therapy confers survival benefit in patients with distant
extent.
PMID- 28412234
TI - Premolar autotransplantation in juvenile dentition: quantitative assessment of
vertical bone and soft tissue growth.
AB - OBJECTIVE: Premolar autotransplantation represents an effective therapeutic
option for the treatment of juvenile dentition with either aquired or congenital
hypodontia. The objective of this prospective clinical study was to
quantitatively assess bone and soft tissue levels after autogenous premolar
transplantation by clinical and radiographic parameters. STUDY DESIGN: In the
study, 26 premolars were transplanted in 20 patients after traumatic tooth loss
(n = 16) or congenital aplasia (n = 10) in the anterior maxilla. Based on
standardized photographic documentation, the relative soft tissue level was
measured compared to the healthy adjacent teeth. Radiographic findings included
evaluation of root resorption, pulp canal obliteration, and relative bone height.
RESULTS: Average survival rate of transplanted premolars (n = 26) was 100% over a
follow-up period of 29 months (range 10-60 months). The relative soft tissue
level significantly increased by +1.1 mm (P < .01). Radiographs showed a tendency
toward vertical bone growth. Continuous root development and signs of pulpal
healing were observed postoperatively in 18 transplants (69.2%). CONCLUSIONS:
Autogenous premolar transplantation represents a safe method to ensure functional
and aesthetic rehabilitation in the anterior maxilla irrespective of the nature
of tooth loss.
PMID- 28412235
TI - Evaluation of the efficacy of a metal artifact reduction algorithm in different
cone beam computed tomography scanning parameters.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of a metal artifact
reduction (MAR) algorithm in cone beam computed tomography (CBCT) images of
dental materials obtained with different field-of-view (FOV) and voxel sizes.
STUDY DESIGN: Two imaging phantoms were custom-made of acrylic resin. Each
phantom had 3 cylinders made of the same dental material: dental amalgam or
copper-aluminum alloy. CBCT scans were obtained separately for each of the
imaging phantoms using the Picasso-Trio CBCT (Vatech, Hwaseong, Republic of
Korea) unit at 4 FOV sizes and 2 voxel sizes. Each imaging phantom was scanned
with and without MAR. All images were evaluated in the OnDemand3D software
(Cybermed, Seoul, Republic of Korea) and image noise (gray value variability) was
calculated as the standard deviation (SD) of the gray values of regions of
interest around the dental material cylinders. Data were compared by the Friedman
test and Dunn test (alpha = 0.05). Intraclass correlation coefficient (ICC) was
calculated to assess intraobserver reliability. RESULTS: MAR significantly
reduced (P < .05) image noise around the dental materials, irrespective of FOV
and voxel sizes, with an ICC of 0.997. CONCLUSIONS: The efficacy of MAR was
similar for the different FOV and voxel sizes studied. Hence, imaging protocols
and the use of MAR algorithm should be based on the selection criteria.
PMID- 28412236
TI - Are dental and jaw changes more prevalent in a Brazilian population with sickle
cell anemia?
AB - OBJECTIVE: The aim of this study was to analyze the prevalence of dental and jaw
changes in individuals with sickle cell anemia (SCA) compared with a control
group from a Brazilian population. STUDY DESIGN: This was a retrospective cross
sectional study. Participants were divided into 2 groups: SCA and control (123
patients per group). Intraoral periapical radiographs were taken. Changes in bone
pattern and dental changes were investigated by using the following radiographic
parameters: (1) trabecular bone (step-ladder or spider web); (2) integrity of the
lamina dura (loss of sharpness and continuity, partial or complete absence, and
increased thickness); and (3) dental changes (pulp chamber, root surface,
periapex, dental form, number, and position). Fisher's exact and chi2 tests were
used to compare frequencies and the Mann-Whitney test was used to compare medians
(P < .05). RESULTS: Step-ladder (P < .001) and spider-web patterns (P < .001) in
trabecular bone of the jaw were more common in individuals with SCA than in the
control group. Loss of lamina dura was more frequent in those with SCA than in
control individuals (P = .021). Dental changes were not different between groups
(P > .05), even though the prevalence of hypotaurodontism was twice as high in
the SCA group as in controls (P = .086). CONCLUSIONS: The prevalence of jaw
changes is higher in individuals with SCA.
PMID- 28412237
TI - Reply to: Details of the participants and medical intervention used in the study
evaluating the effect of a mouth exercising device on burning sensation in oral
submucous fibrosis.
PMID- 28412238
TI - Chitosan-modified PLGA nanoparticles tagged with 5TR1 aptamer for in vivo tumor
targeted drug delivery.
AB - In this study, we reported epirubicin (Epi) encapsulated nanoparticles (NPs)
formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid)
(PLGA) modified with chitosan (CS) through a physical adsorption method. Using
chitosan, the solubility and surface charge of PLGA was modified to make
efficient drug carriers for cancer cells. To improve the anti-tumor efficacy, we
developed targeted therapy of tumor cells using a 5TR1 DNA aptamer (Apt) against
the MUC1 receptor. To prove the MUC1 receptor-mediated uptake of Epi-PLGA-CS-Apt
NPs in the cells, competition experiments were carried out. In vitro experiments,
cytotoxicity assay and fluorescence uptake assay demonstrated that fabricated NPs
with or without aptamers showed significantly high therapeutic efficiency in MCF7
cells (breast cancer cell) compared with free Epi, while in BALB/c mice bearing
C26 cells (murine colon carcinoma cell), targeted NP groups exhibited significant
tumor growth inhibition and higher inclination to tumor compared with non
targeted NPs. Hence, our in vivo results revealed that non-targeted NPs may
diffuse away from the tumor site and release Epi in the extracellular space and
decrease concentration of the drug in the targeted tissue. This study indicated
Epi-PLGA-CS-Apt has great potential as a promising nanoplatform for in vivo
cancer therapy and could be of great value in medical use.
PMID- 28412239
TI - microRNAs as cancer therapeutics: A step closer to clinical application.
AB - During the last decades, basic and translational research has enabled great
improvements in the clinical management of cancer. However, scarcity of complete
remission and many drug-induced toxicities are still a major problem in the
clinics. Recently, microRNAs (miRNAs) have emerged as promising therapeutic
targets due to their involvement in cancer development and progression. Their
extraordinary regulatory potential, which enables regulation of entire signalling
networks within the cells, makes them an interesting tool for the development of
cancer therapeutics. In this review we will focus on miRNAs with experimentally
proven therapeutic potential, and discuss recent advances in the technical
development and clinical evaluation of miRNA-based therapeutic agents.
PMID- 28412240
TI - The level of effort, rather than muscle exercise intensity determines strength
gain following a six-week training.
AB - AIM: This study investigated the effect of voluntary motor effort during a low
intensity (30% maximal voluntary contraction [MVC]) muscle exercise training
program on increasing muscle strength. MATERIALS AND METHODS: Eighteen young and
healthy individuals were randomly assigned to one of three groups: high mental
effort (HME), low mental effort (LME), or a no-training control (CTRL) group.
Training lasted for 6weeks (15min/day, 5days/week). The participants' right-elbow
flexor muscle strength was measured before and after the training program. KEY
FINDINGS: After training, the HME group gained 20.47+/-8.33% (P=0.01) strength
while the LME and CTRL groups had negligible strength changes (1.89+/-0.96% and
3.27+/-2.61%, respectively; P>0.05) despite muscle contraction intensity (30%
MVC) sustained during training was the same for the HME and LME groups. These
results suggest that the level of effort involved in resistance exercise training
plays a critical role in determining the amount of strength augmentation.
SIGNIFICANCE: The finding that high effort combined with low-level physical
exercise training can significantly increase muscle strength has rehabilitation
applications as many patients and frail older adults have difficulties in
participating in high-intensity exercise training such as lifting heavy weights.
High effort plus low-level muscle exercise might serve as a safe training regimen
for effective muscle strengthening in vulnerable populations.
PMID- 28412241
TI - Cathepsin L silencing increases As2O3 toxicity in malignantly transformed
pilocytic astrocytoma MPA58 cells by activating caspases 3/7.
AB - Low-grade, pilocytic astrocytomas are treated by resection, but additional
therapy is necessary for those tumors with anaplastic features. Arsenic trioxide
(As2O3) is emerging as an effective chemotherapeutic agent for treatment of
malignant glioblastoma multiforme, where Cathepsin L silencing enables lower,
less harmful As2O3 concentrations to achieve the desired cytotoxic effect. Here,
we evaluated the effects of As2O3 combined with stable Cathepsin L shRNA
silencing on cell viability/metabolic activity, and apoptosis in primary cultures
of recurrent malignantly transformed pilocytic astrocytoma (MPA). These cells
expressed high Cathepsin L levels, and when grown as monolayers and spheroids,
they were more resistant to As2O3 than the U87MG glioblastoma cell line. Caspases
3/7 activity in MPA58 spheroids was not significantly affected by As2O3, possibly
due to higher chemoresistance of primary biopsy tissue of less malignant
astrocytoma versus the malignant U87MG cell line. However, As2O3 treatment was
cytotoxic to MPA spheroids after silencing of Cathepsin L expression. While
Cathepsin L silencing only slightly decreased the live/dead cell ratio in As2O3
treated MPA-si spheroids under our experimental conditions, there was an increase
in As2O3-mediated apoptosis in MPA-si spheroids, as indicated by elevated
caspases 3/7 activity. Therefore, Cathepsin L silencing by gene manipulation can
be applied when a more aggressive approach is needed in treatment of pilocytic
astrocytomas with anaplastic features.
PMID- 28412242
TI - 14-3-3gamma regulates Copine1-mediated neuronal differentiation in HiB5
hippocampal progenitor cells.
AB - Copine1 (CPNE1), known as a calcium-dependent membrane-binding protein, has
tandem C2 domains and an A domain. We previously demonstrated that CPNE1 directly
induces neuronal differentiation via Protein kinase B (AKT) phosphorylation in
the hippocampal progenitor cell line, HiB5. To better understand its cellular
function, we carried out a yeast two-hybrid screening to find CPNE1 binding
partners. Among the identified proteins, 14-3-3gamma appears to directly interact
with CPNE1. Between CPNE1 and 14-3-3gamma, the physical interaction as well as
the specific binding regions of CPNE1 was confirmed in vitro and in vivo.
Furthermore, among the seven 14-3-3 isotypes, only 14-3-3gamma directly interacts
with CPNE1. Our results also demonstrate that AKT phosphorylation, neurite
outgrowth and expression of the neuronal marker protein are increased when 14-3
3gamma is overexpressed in CPNE1 high expressed HiB5 cells. Furthermore, the
neighboring Ser54 amino acids residue of C2A domain in CPNE1 has an important
role in binding with 14-3-3gamma, and in differentiation-related function of
CPNE1. Moreover, mutation of Ser54 amino acids residue in CPNE1 effectively
decreased association with 14-3-3gamma and neuronal differentiation of HiB5
cells. Collectively, our findings indicate that 14-3-3gamma regulates the
differentiation ability of CPNE1 through the binding with C2A domain of CPNE1 in
HiB5 cells.
PMID- 28412243
TI - Macrophage conditioned medium induced cellular network formation in MCF-7 cells
through enhanced tunneling nanotube formation and tunneling nanotube mediated
release of viable cytoplasmic fragments.
AB - Infiltrating macrophages in tumor microenvironment, through their secreted
cytokines and growth factors, regulate several processes of cancer progression
such as cancer cell survival, proliferation, invasion, metastasis and
angiogenesis. Recently, intercellular cytoplasmic bridges between cancer cells
referred as tunneling nanotubes (TNTs) have been recognized as novel mode of
intercellular communication between cancer cells. In this study, we investigated
the effect of inflammatory mediators present in conditioned medium derived from
macrophages on the formation of TNTs in breast adenocarcinoma cells MCF-7.
Results show that treatment with macrophage conditioned medium (MphiCM) not only
enhanced TNT formation between cells but also stimulated the release of
independently migrating viable cytoplasmic fragments, referred to as microplasts,
from MCF-7 cells. Time lapse microscopy revealed that microplasts were released
from parent cancer cells in extracellular space through formation of TNT-like
structures. Mitochondria, vesicles and cytoplasm could be transferred from parent
cell body to microplasts through connecting TNTs. The microplasts could also be
resorbed into the parent cell body by retraction of the connecting TNTs.
Microplast formation inhibited in presence cell migration inhibitor, cytochalasin
B. Notably by utilizing migratory machinery within microplasts, distantly located
MCF-7 cells formed several TNT based intercellular connections, leading to
formation of physically connected network of cells. Together, these results
demonstrate novel role of TNTs in microplast formation, novel modes of TNT
formation mediated by microplasts and stimulatory effect of MphiCM on cellular
network formation in MCF-7 cells mediated through enhanced TNT and microplast
formation.
PMID- 28412245
TI - CXCR5+CD8+ T cells infiltrate the colorectal tumors and nearby lymph nodes, and
are associated with enhanced IgG response in B cells.
AB - Colorectal cancer is the third most prevalent cancer type worldwide and
contributes to a significant percentage of cancer-related mortality. Recent
studies have shown that the CXCR5+CD8+ T cells present more potent
proinflammatory function than CXCR5-CD8+ T cells in chronic virus infections and
in follicular lymphoma, but the role of CXCR5+CD8+ T cells in colorectal cancer
is yet unclear. In this study, we demonstrated that CXCR5+CD8+ T cells were very
rare in peripheral blood mononuclear cells from healthy and colorectal cancer
individuals, but were significantly enriched in resected tumors and tumor
associated lymph nodes. Compared to CXCR5-CD8+ T cells, the CXCR5+CD8+ T cells
demonstrated significantly higher Bcl-6 expression and lower Blimp1 expression,
suggesting that CXCR5+CD8+ T cells might represent a memory CD8+ T cell subset.
CXCR5+CD8+ T cells also enhanced the IgG expression by autologous B cells. Under
ex vivo condition, the CXCR5+CD8+ T cells demonstrated lower degranulation,
TNFalpha expression and IFNgamma expression than CXCR5-CD8+ T cells. However,
after PMA + ionomycin stimulation, the degranulation and TNFalpha expression by
CXCR5+CD8+ T cells were significantly elevated to a level comparable with CXCR5
CD8+ T cells, whereas the IFNgamma expression by PMA + ionomycin-stimulated
CXCR5+CD8+ T cells were significantly higher than that by CXCR5-CD8+ T cells.
Following long-term TCR-stimulation, CXCR5+CD8+ T cells demonstrated
significantly more potent proliferation capacity and higher IFNgamma expression
than CXCR5-CD8+ T cells. TCR-stimulated CXCR5+CD8+ T cells also showed a gradual
downregulation in CXCR5 expression. We further found that TCR-stimulated
CXCR5+CD8+ T cells demonstrated higher granzyme B production and induced more
specific lysis of autologous tumor cells than CXCR5-CD8+ T cells. Together, these
data demonstrate that CXCR5+CD8+ T cells represent a significant CD8+ T cell
subset in colorectal tumors and have the potential to contribute to antitumor
immunity, but their specific roles require further studies in vivo.
PMID- 28412246
TI - Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated
cardiac protection.
AB - Bone marrow-derived mesenchymal stem cells (BM-MSCs) contribute to myocardial
repair after myocardial infarction (MI) by secreting a panel of growth factors
and cytokines. This study was to investigate the potential mechanisms of the
nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) in
regulation of the profiles of BM-MSCs secretion and compare the therapeutic
efficacy of NUCKS-/-- and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion
profiles between NUCKS-/-- and WT-BM-MSCs under hypoxia (1%O2) were analyzed.
Gene function analysis showed that compared with WT-BM-MSCs-conditioned medium
(CdM), some genes over-presented in NUCKS-/--BM-MSCs-CdM were closely associated
with inflammatory response, regulation of cell proliferation, death, migration
and secretion. Notably, VEGFa in NUCKS-/--BM-MSCs-CdM was higher than that of WT
BM-MSCs-CdM. WT-BM-MSCs and NUCKS-/--BM-MSCs were transplanted into the peri
infarct region in mice of MI. At 4 weeks after cell transplantation, NUCKS-/-- or
WT-BM-MSCs group significantly improved heart function and vessels density and
reduced infarction size and apoptosis of cardiomyocytes. Furthermore, NUCKS-/--BM
MSCs provided better cardioprotective effects than WT-BM-MSCs against MI. Our
study demonstrates that depletion of NUCKS enhances the therapeutic efficacy of
BM-MSCs for MI via regulating the secretion.
PMID- 28412244
TI - A central role for cadherin signaling in cancer.
AB - Cadherins are homophilic adhesion molecules with important functions in cell-cell
adhesion, tissue morphogenesis, and cancer. In epithelial cells, E-cadherin
accumulates at areas of cell-cell contact, coalesces into macromolecular
complexes to form the adherens junctions (AJs), and associates via accessory
partners with a subcortical ring of actin to form the apical zonula adherens
(ZA). As a master regulator of the epithelial phenotype, E-cadherin is essential
for the overall maintenance and homeostasis of polarized epithelial monolayers.
Its expression is regulated by a host of genetic and epigenetic mechanisms
related to cancer, and its function is modulated by mechanical forces at the
junctions, by direct binding and phosphorylation of accessory proteins
collectively termed catenins, by endocytosis, recycling and degradation, as well
as, by multiple signaling pathways and developmental processes, like the
epithelial to mesenchymal transition (EMT). Nuclear signaling mediated by the
cadherin associated proteins beta-catenin and p120 promotes growth, migration and
pluripotency. Receptor tyrosine kinase, PI3K/AKT, Rho GTPase, and HIPPO
signaling, are all regulated by E-cadherin mediated cell-cell adhesion. Finally,
the recruitment of the microprocessor complex to the ZA by PLEKHA7, and the
subsequent regulation of a small subset of miRNAs provide an additional mechanism
by which the state of epithelial cell-cell adhesion affects translation of target
genes to maintain the homeostasis of polarized epithelial monolayers.
Collectively, the data indicate that loss of E-cadherin function, especially at
the ZA, is a common and crucial step in cancer progression.
PMID- 28412247
TI - Activation of phospholipase C-gamma1 and translocation of phosphatidylinositol
3,4,5-trisphosphate 3-phosphatase contribute to GL-V9-induced apoptosis in human
gastric cancer cells.
AB - Gastric cancer is the most common type of tumor in developing countries and the
fourth most frequently diagnosed cancer worldwide. Here, we demonstrated the
apoptotic effects of GL-V9 on several human gastric cancer cells and selected MGC
803 cells to uncover the underlying mechanism. GL-V9 elevated Bax/Bcl-2 ratio,
abated mitochondrial membrane potential and triggered the onset of apoptotic
execution in MGC-803 cells. Our research revealed that CHOP silencing could not
inhibit apoptosis, neither could it block Ca2+ release, suggesting that GL-V9
induced apoptosis was independent of CHOP. Furthermore, GL-V9 increased
mitochondrial Ca2+ uptake through 1,4,5-triphosphate (IP3) receptor via the
activation of phospholipase C-gamma1 and the translocation of
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase from nucleus to
endoplasmic reticulum. Moreover, in-vivo studies indicated that GL-V9 exhibited
significant MGC-803 xenografts regression in nude mice with low systemic
toxicity. In conclusion, GL-V9 could induce apoptosis in gastric cancer cells,
and would be a promising therapeutical agent against gastric cancer.
PMID- 28412248
TI - Mass Spectrometry Reveals Respiratory Viral Infection Biomarkers.
PMID- 28412250
TI - Mucosal Lining Fluid Biomarkers in Asthma: Basis for Rational Use of New Targeted
Therapies?
PMID- 28412249
TI - The T-LAK Cell-originated Protein Kinase Signal Pathway Promotes Colorectal
Cancer Metastasis.
AB - Approximately 90% of all cancer deaths arise from the metastatic dissemination of
primary tumors. Metastasis is the most lethal attribute of colorectal cancer. New
data regarding the molecules contributing to the metastatic phenotype, the
pathways they control and the genes they regulate are very important for
understanding the processes of metastasis prognosis and prevention in the clinic.
The purpose of this study was to investigate the role of T-LAK cell-originated
protein kinase (TOPK) in the promotion of colorectal cancer metastasis. TOPK is
highly expressed in human metastatic colorectal cancer tissue compared with
malignant adenocarcinoma. We identified p53-related protein kinase (PRPK) as a
new substrate of TOPK. TOPK binds with and phosphorylates PRPK at Ser250 in vitro
and ex vivo. This site plays a critical role in the function of PRPK. Cell lines
stably expressing mutant PRPK (S250A), knockdown TOPK, knockdown PRPK or
knockdown of both TOPK and PRPK significantly inhibited liver metastasis of human
HCT116 colon cancer cells in a xenograft mouse model. Therefore, we conclude that
TOPK directly promotes metastasis of colorectal cancer by modulating PRPK. Thus,
these findings may assist in the prediction of prognosis or development of new
therapeutic strategies against colon cancer.
PMID- 28412253
TI - An Unusual Cause of ST-Segment Elevation Myocardial Infarction.
PMID- 28412251
TI - c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in
Prostate Cancer Affecting Key Gene Networks.
AB - Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The
androgen receptor (AR), a ligand-activated transcription factor, constitutes the
main drug target for advanced cases of the disease. However, a variety of other
transcription factors and signaling networks have been shown to be altered in
patients and to influence AR activity. Amongst these, the oncogenic transcription
factor c-Myc has been studied extensively in multiple malignancies and elevated
protein levels of c-Myc are commonly observed in PCa. Its impact on AR activity,
however, remains elusive. In this study, we assessed the impact of c-Myc
overexpression on AR activity and transcriptional output in a PCa cell line model
and validated the antagonistic effect of c-MYC on AR-targets in patient samples.
We found that c-Myc overexpression partially reprogrammed AR chromatin occupancy
and was associated with altered histone marks distribution, most notably H3K4me1
and H3K27me3. We found c-Myc and the AR co-occupy a substantial number of binding
sites and these exhibited enhancer-like characteristics. Interestingly, c-Myc
overexpression antagonised clinically relevant AR target genes. Therefore, as an
example, we validated the antagonistic relationship between c-Myc and two AR
target genes, KLK3 (alias PSA, prostate specific antigen), and Glycine N
Methyltransferase (GNMT), in patient samples. Our findings provide unbiased
evidence that MYC overexpression deregulates the AR transcriptional program,
which is thought to be a driving force in PCa.
PMID- 28412254
TI - Percutaneous Coronary Intervention for Treatment of Paraganglioma With Coronary
Vascularization.
PMID- 28412252
TI - Replicative senescence promotes prothrombotic responses in endothelial cells:
Role of NADPH oxidase- and cyclooxygenase-derived oxidative stress.
AB - Endothelial senescence has been suggested to promote endothelial dysfunction in
age-related vascular disorders. This study evaluated the prothrombotic properties
of senescent endothelial cells (ECs) and the underlying mechanism. Serial
passaging from passage (P)1 to P4 (replicative senescence) of porcine coronary
artery ECs, or treatment of P1 ECs with the endothelial nitric oxide synthase
(eNOS) inhibitor L-NAME (premature senescence) induced acquisition of markers of
senescence including increased senescence-associated-beta-galactosidase (SA-beta
gal) activity and p53, p21, p16 expression. Approximately 55% of P3 cells were
senescent with a high level oxidative stress, and decreased eNOS-derived nitric
oxide (NO) formation associated with increased expression of NADPH oxidase
subunits (gp91phox, p47phox), cyclooxygenase (COX)-2 but not COX-1, and a
decreased eNOS expression leading to a reduced ability of ECs to inhibit platelet
aggregation. P3 cells also presented increased expression and activity of tissue
factor (TF), a key initiator of the coagulation cascade. Treatment of senesecent
cells with a NADPH oxidase inhibitor (VAS-2870) or by a COX inhibitor
(indomethacin) reduced oxidative stress, decreased TF activity and expression,
and reduced the expression of gp91phox, p47phox and COX-2 and restored the
ability of ECs to inhibit effectively platelet aggregation. Thus, replicative
endothelial senescence promotes a prothrombotic response involving the down
regulation of the protective NO pathway and the upregulation of the NADPH oxidase
and COXs-dependent oxidative stress pathway promoting TF expression and
activity.
PMID- 28412255
TI - Mini-Chimney Technique for Subclavian Artery Iatrogenic Bleeding.
PMID- 28412257
TI - Complete Healing of Spontaneous Coronary Artery Dissection Demonstrated by
Optical Coherence Tomography in a Young Postpartum Female Presenting With Acute
Coronary Syndrome.
PMID- 28412256
TI - Procedural and Long-Term Outcomes of Percutaneous Coronary Intervention for In
Stent Chronic Total Occlusion.
AB - OBJECTIVES: The study sought to investigate the long-term outcomes and predictors
of adverse events of percutaneous coronary intervention (PCI) for in-stent
chronic total occlusion (IS-CTO). BACKGROUND: IS-CTO PCI has traditionally been
associated with suboptimal success rates. METHODS: We performed a multicenter
registry of consecutive patients undergoing CTO PCI at 3 specialized centers.
Patients were divided in IS-CTO and de novo CTO. The primary endpoint (major
adverse cardiac events [MACE]) was a composite of cardiac death, target-vessel
myocardial infarction, and ischemia-driven target-vessel revascularization (TVR)
on follow-up. Independent predictors of MACE were sought with Cox regression.
RESULTS: We included 899 patients (n = 111 IS-CTO, n = 788 de novo CTO). Baseline
clinical and angiographic characteristics were balanced between the 2 groups.
Overall mean J-CTO (Japanese-Chronic Total Occlusion) score was 1.88 +/- 1.24 and
mean PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total
Occlusion Intervention-CTO) score was 1.04 +/- 0.88. Antegrade wire escalation
was used in 59.0% of IS-CTO and 48.1% of de novo CTO patients (p = 0.08).
Procedural success was achieved in 86.5% in both groups (p = 0.99). After a
median follow-up of 471 (interquartile range: 354 to 872) days, MACE were
observed in 20.8% versus 13.9% in IS-CTO versus de novo CTO (p = 0.07), driven by
TVR (16.7% vs. 9.4%; p = 0.03). IS-CTO was an independent predictor of MACE
(hazard ratio: 2.16; 95% confidence interval: 1.18 to 3.95; p = 0.01), together
with prior surgical revascularization and renal function, CTO PCI indicated for
acute coronary syndrome, number of diseased vessels, and PROGRESS-CTO score.
CONCLUSIONS: Procedural success was high and similar in patients with IS-CTO, as
compared with de novo CTO. However, IS-CTO was independently associated with MACE
(driven by TVR) on follow-up.
PMID- 28412258
TI - In-Stent CTO, Not as Easy as it Looks.
PMID- 28412259
TI - Right Aortic Arch With Left-Sided Arteria Lusoria: A Challenge for Radial
Interventionalists.
PMID- 28412260
TI - Is Oral Biopsy Associated With Change in Tobacco or Alcohol Use?
AB - PURPOSE: Tobacco and alcohol remain the predominant risk factors for oral cancer,
but the relation between having an oral biopsy and cessation of these risk
factors is unknown. Therefore, this investigation examined whether there might be
an association between oral biopsy and change in risk factor use. MATERIALS AND
METHODS: A survey was sent to a cohort consisting of a consecutive sample of
subjects identified in the University of North Carolina Oral Pathology database.
The predictor variable was oral biopsy diagnosis, with 3 levels consisting of
hyperkeratosis, dysplasia, or carcinoma. The outcome variable was change in risk
factor use, coded as "no change in usage," "decreased usage" or "quit." Other
study variables included age, gender, and race. The proportional odds model was
used to assess the effect of explanatory variables on change in use, and the P
value was set at .05. RESULTS: The response rate was 37.4% for a total sample of
605 subjects. White non-Hispanics composed 85% of respondents and women composed
49.5%, with no significant difference among diagnostic categories. The global
test for change in cigarette use was significant, with age contributing to
variability in behavioral change. Although not statistically significant, larger
percentages of patients with more severe diagnoses quit cigarettes and alcohol
following biopsy. The youngest respondents were 3.7 times more likely not to quit
before biopsy or to continue to smoke following biopsy (95% confidence interval,
1.98-6.91). CONCLUSION: The results of this study suggest that oral biopsy
provides an ideal opportunity to focus on risk factor cessation. Different
diagnoses provide objective data on which to base a discussion about
carcinogenesis and the roles played by the risk factors in this process.
Differences in risk factor cessation associated with demographics emphasize the
need for all clinicians to address cessation with all patients.
PMID- 28412261
TI - Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging-An Alternative to
Fine Needle Biopsy or Only an Adjunct Test in Preoperative Differential
Diagnostics of Malignant and Benign Parotid Tumors?
AB - PURPOSE: The role of dynamic magnetic resonance imaging (MRI) in the preoperative
differential diagnostics of parotid tumors is unclear. The aim of this study was
to compare the accuracy of dynamic MRI and routinely used fine needle biopsy
examination in the preoperative differentiation of malignant and benign parotid
tumors. MATERIALS AND METHODS: The study included 100 consecutive patients with
parotid tumors treated surgically at the authors' center. Accuracy of dynamic MRI
and fine needle biopsy examinations in the differential diagnostics of malignant
and benign lesions was verified against the gold standard (ie, final histologic
diagnosis). RESULTS: Based on histopathologic examination of surgical specimens,
19 tumors were eventually diagnosed as malignant lesions and 81 were diagnosed as
benign. Preoperative fine needle biopsy examination yielded 9 true positive, 70
true negative, 11 false positive, and 10 false negative results, which
corresponded to 47.4 and 86.4% sensitivity and specificity, respectively. The
most commonly established preoperative diagnosis for 10 tumors that were
misdiagnosed as benign based on examination of biopsy specimens was pleomorphic
adenoma (n = 10). Dynamic MRI examination yielded 17 true positive, 81 true
negative, 2 false negative, and 0 false positive results, which corresponded to
89.5% sensitivity and 100% specificity. CONCLUSIONS: These results suggest that
dynamic MRI is highly accurate in the detection of malignant parotid tumors.
However, taking into account the high cost and limited availability of this
examination, its logical application seems to be verification of preoperative
diagnoses in patients whose fine needle biopsy examination turned out to be
nondiagnostic or showed pleomorphic adenoma.
PMID- 28412262
TI - Surge of Surgeons? Surely!
PMID- 28412263
TI - Oculocardiac Reflex in an Orbital Fracture Without Entrapment.
AB - Large orbital fractures in older patients are infrequently associated with an
exaggerated oculocardiac reflex. This report describes the case of a patient in
his 40s with a large right orbital floor and medial wall fracture without
radiographic evidence of extraocular muscle compression or entrapment who
developed severe nausea and bradycardia with movement of his affected eye. The
patient exhibited bradycardia to 17 beats per minute during the initial
examination and was taken urgently to the operating room for reconstruction of
the right orbital floor and medial wall. Additional episodes of bradycardia
intraoperatively were responsive to glycopyrrolate. After the procedure, the
patient's pain was decreased, a normal range of motion was restored, and the
bradycardia and nausea resolved. An explanation for induction of the oculocardiac
reflex is considered in the absence of clinical or radiologic entrapment because
large orbital fractures are not often considered to induce this reflex.
PMID- 28412264
TI - ACS Fellowship for Single-Degree Oral and Maxillofacial Surgeons.
PMID- 28412265
TI - One-Stage Supramaximal Full-Thickness Wedge Resection of Vascular Lip Anomalies.
AB - PURPOSE: Vascular lip anomalies include infantile hemangiomas, venous
malformations, and arteriovenous malformations. Surgical management can be
complicated by alterations in horizontal length, vertical height, and lip
thickness from the underlying pathology. Additional reconstructive challenges
include preservation of oral continence, vermillion definition, and the sublabial
sulcus. This report describes a technique of supramaximal single-stage full
thickness wedge resection of these lesions. MATERIALS AND METHODS: A
retrospective study approved by the institutional review board of patients who
underwent full-thickness resection of vascular lip anomalies from December 2007
through February 2013 was performed. Patient demographics, final diagnosis,
preoperative treatment, examination findings (pre- and postoperative),
intraoperative management, and follow-up findings were reviewed. RESULTS:
Eighteen patients (9 female) with a mean age of 25 +/- 19.8 years (range, 3 to 70
yr) were identified. Underlying pathologies were arteriovenous malformation (6),
port wine stain with secondary soft tissue hypertrophy (6), capillary
malformation (1), venous malformation (3), and infantile hemangioma (2). Prior
treatments included embolization, lasers, surgical excision, steroids, and
propranolol; 8 patients were treatment naive. All patients underwent a single or
double pentagonal-shaped wedge resection of the involved upper or lower lip. An
average of 3.75 cm (41.7%; range, 20 to 70%) of horizontal lip length was
excised. Four patients required additional concomitant debulking of the
vermillion. No intraoperative complications were noted. Postoperatively, 1
patient developed wound dehiscence at 12 days and another had a midline
depression with mild oral incontinence. Follow-up averaged 1,074 days (range, 371
to 1,777 days) and patients and their parents reported a high degree of
satisfaction with the improvement in lip appearance and symmetry except for 1
patient who required further debulking. The sublabial sulcus and vermillion and
cutaneous definition were preserved in all cases. CONCLUSION: Despite the
traditional recommendation that no more than 30% of lip length be surgically
removed, vascular lip anomalies result in tissue hypertrophy, horizontal
elongation, ectropion labii, and tissue expansion that allow up to 70% of the lip
to be excised.
PMID- 28412266
TI - Hyperparathyroidism Diagnosed Due to Brown Tumors of the Jaw: A Case Report and
Literature Review.
AB - This report describes the case of a 42-year-old woman who consulted with a
maxillofacial specialist for pain and an exophytic lesion in the maxilla. Biopsy
examination disclosed a bone cyst with abundant giant cells, and head and neck
computed tomography was performed. A diagnosis of brown tumor in the maxilla and
mandible was made, and primary hyperparathyroidism (parathyroid adenoma) was
determined as the origin of the bone lesions. The patient underwent a left
superior parathyroidectomy, which resolved the hormonal disorder (as determined
by normal calcium and parathyroid hormone levels) and the brown tumors, which
appeared to have mineralized at 1-year follow-up computed tomography. Dental
implant rehabilitation was performed at the sites of the absent tumors. A
systematic review of articles published in the English-language medical
literature through the PubMed and Medline databases yielded 40 articles
(published from 1969 through 2016) on 45 cases of hyperparathyroidism associated
with the location of a brown tumor in the mandible or maxilla.
PMID- 28412267
TI - Pamidronate Disodium Leads to Bone Necrosis via Suppression of Wnt/beta-Catenin
Signaling in Human Bone Marrow Mesenchymal Stem Cells In Vitro.
AB - PURPOSE: Pamidronate disodium-associated bone necrosis is poorly understood at
the cellular and molecular levels. This study proposes a pathway leading to the
pamidronate disodium-mediated inhibition of osteogenic differentiation of human
bone marrow mesenchymal stem cells (BMMSCs) derived from the mandible in vitro.
MATERIALS AND METHODS: Primary human BMMSCs were isolated from the mandible and
marrow tissue. A proliferation assay was performed to determine the experimental
concentration of pamidronate disodium. Alkaline phosphatase (ALP) activity, ALP
staining, and Alizarin red S (ARS) staining were assessed after treatment with
pamidronate disodium (0, 0.1, 0.5, 1, 5, 10 MUg/mL). Quantitative real-time
polymerase chain reaction and western blotting specific for Wnt and beta-catenin
signaling genes or proteins were performed after treatment with pamidronate
disodium 0.5 MUg/mL. Wnt3a was used to observe the osteogenic differentiation of
BMMSCs during treatment with pamidronate disodium 0.5 MUg/mL. RESULTS: As
expected, pamidronate disodium 1, 5, and 10 MUg/ml were unfavorable for BMMSC
growth (P < .05), whereas 0.1 and 0.5 MUg/mL did not affect BMMSC growth (P >=
.05). BMMSCs treated with pamidronate disodium 0.5 MUg/mL had lower ALP activity,
ALP staining, and ARS staining (P < .05), and BMMSCs treated with low
concentrations (<0.5 MUg/mL) of pamidronate disodium had the same levels of ALP
activity, ALP staining, and ARS staining as the control (0 MUg/mL). Pamidronate
disodium 0.5 MUg/mL decreased the expression of genes and proteins involved in
Wnt and beta-catenin signaling. BMMSCs with Wnt3a and pamidronate disodium 0.5
MUg/mL had higher ALP activity, ALP staining, and ARS staining (P < .05).
CONCLUSIONS: Pamidronate disodium inhibited Wnt and beta-catenin signaling, which
controls osteogenic differentiation in BMMSCs. Wnt3a, a Wnt and beta-catenin
signaling activator, reversed the negative effects caused by pamidronate disodium
to salvage the osteogenic defect in BMMSCs.
PMID- 28412268
TI - How Is Third Molar Status Associated With the Occurrence of Mandibular Angle and
Condyle Fractures?
AB - PURPOSE: Third molars (M3s) have been hypothesized to be associated with the risk
of mandibular angle fracture and mandibular condylar fracture. The authors
systematically estimated the relative risk (RR) of M3 status for the development
of mandibular angle fracture and mandibular condylar fracture through a meta
analysis of cohort studies. MATERIALS AND METHODS: In this systematic review, the
PubMed, EMBASE, and Cochrane Library databases were searched from inception to
October 2016. The predictor of risk was the presence or absence of M3s. The
primary outcome was the RR of mandibular angle or condylar fracture. A fixed- or
a random-effects model was applied to evaluate the pooled risk estimates.
Sensitivity analysis also was performed to identify the potential sources of
heterogeneity. Publication bias was assessed by the Begg and Egger tests.
RESULTS: Overall, 13 retrospective cohort studies were included. Of these, 13
reported the association between M3s and mandibular angle fracture, and 5
reported the association with mandibular condylar fracture. Patients with M3s had
an increased risk of mandibular angle fractures (RR = 2.63; 95% confidence
interval [CI], 2.15-3.21) but a decreased risk of mandibular condylar fractures
(RR = 0.47; 95% CI, 0.25-0.86). Substantial heterogeneity in the risk estimates
was found. No evidence of publication bias was found. CONCLUSION: The present
meta-analysis provides further evidence associating the presence of M3s with an
increased risk of mandibular angle fractures and a simultaneously decreased risk
of mandibular condylar fracture. Because of potentially more serious
complications associated with condylar fracture, clinicians should carefully
consider the decision to remove M3s to decrease the risk of mandibular angle
fracture.
PMID- 28412269
TI - Towards an understanding of the isotype-specific functions of tubulin in neurons:
Technical advances in tubulin expression and purification.
AB - Microtubules are cytoskeletal filaments critical for determining the complex
morphology of neurons, as well as the basic architecture and organization of
mitosis in all eukaryotic cells. Microtubules in humans are composed of 8 alpha-
and 9 beta-tubulin isotypes, each of which is encoded by different members of a
multi-gene family. The expression pattern of tubulin isotypes, in addition to
isotype-specific post-translational modifications, is thought to be critical for
the morphogenesis of axons and dendrites. Recent studies revealed that several
neurodevelopmental disorders are caused by mutations of specific tubulin
isotypes, suggesting that each tubulin isotype has distinct functions. Therefore,
in vitro and in vivo functional analyses of tubulin isotypes are important to
understand the pathogenesis of developmental disorders. Likewise, analysis of
developmental disorders may clarify the function of different tubulin isotypes.
In this respect, both the preparation of specific tubulin isotypes and of
specific mutant tubulin proteins is critical to understanding the function of
tubulin. In the last 20 years, various methods have been developed to study
functional differences between tubulin isotypes and the functional defects caused
by tubulin mutations. These technical achievements have been discussed in this
review. The function of tubulin/microtubules in neuronal morphogenesis as
revealed through these techniques has also been described.
PMID- 28412270
TI - How Surgeons Conceptualize Talent: A Qualitative Study Using Sport Science as a
Lens.
AB - OBJECTIVES: Debates prevail regarding the definition of surgical talent, and how
individuals with the potential to become talented surgeons can be identified and
developed. However, over the past 30 years, talent has been studied extensively
in other domains. The objectives of this study is to explore notions of talent in
surgery and sport in order to investigate if the field of surgical education can
benefit from expanding its view on talented performances. Therefore, this study
aims to use the sport literature as a lens when exploring how surgeons
conceptualize and define talent. DESIGN: Semi-structured interviews were
conducted with a sample of 11 consultant surgeons from multiple specialties. We
used constructivist grounded theory principles to explore talent in surgery.
Ongoing data analysis refined the theoretical framework and iteratively informed
data collection. Themes were identified iteratively using constant comparison.
SETTING: The setting included 8 separate hospitals across Canada and Denmark.
PARTICIPANTS: A total of 11 consultant surgeons from 6 different surgical
subspecialties (urology, orthopedic surgery, colorectal surgery, general surgery,
vascular surgery, head & neck surgery) were included. RESULTS: We identified
three key elements for conceptualizing surgical talent: (1) Individual skills
makes the surgical prospect "good", (2) a mixture of skills gives the surgical
prospect the potential to become talented, and (3) becoming talented may rely on
the fit between person and environment. CONCLUSION: We embarked on a study aimed
at understanding talent in surgery. Talent is a difficult construct to agree on.
Whether in medicine or sports, debates about talent will continue to persist, as
we all perceive talent differently. While we heard different opinions, three key
ideas summarize our participants' discussions regarding surgical talent. These
findings resonate with the holistic ecological approach from sport science and
hence highlight the limits of a reductionist approach while favoring the
individual-environment system as the minimal ontology for describing talented
performances.
PMID- 28412271
TI - Impact of a new distal attachment on colonoscopy performance in an academic
screening center.
AB - BACKGROUND AND AIMS: Distal attachments placed on the colonoscope tip may
positively affect performance by assisting insertion and polyp detection. The
original Endocuff (ARC Medical Design, Leeds, United Kingdom) appears to improve
adenoma detection rate (ADR), but no data assess the performance of the second
generation Endocuff Vision. METHODS: A pilot service evaluation study (April 2013
to September 2014) was conducted on patients with positive fecal occult blood
tests within the National Bowel Cancer Programme during 3 consecutive periods:
precuff/no device used, during-cuff/device used, and postcuff/no device used.
During the middle period the use of the Endocuff Vision by the 4 screening
accredited colonoscopists was discretional (nonrandomized design). Data were
analyzed using pairwise comparisons during the 3 designated periods to examine
key performance indicators: adenoma detection, procedural time, sedation
requirements, and patient comfort. RESULTS: Four hundred ten complete
colonoscopies were performed (137 precuff, 136 cuff, and 137 postcuff period).
Overall, there was a notable increase in the mean ADR of 16% (P < .03) and in the
mean number adenoma per procedure (MAP) of 83% (P = .007) from precuff to cuff
period. The mean cecal intubation time was statistically lower during the cuff
period (7 minutes) in relation to the precuff period (8 minutes; reduction of
12.5%, P = .002) and the postcuff period (9 minutes; increase of 28.6%, P =
.002). The mean negative colonoscopy withdrawal time was also significantly lower
during the cuff period (8 minutes, 30 seconds) when compared with the precuff (12
minutes) or postcuff period (9 minutes, 45 seconds; P <= .001). Multivariate
regression analysis showed that the use of the Endocuff Vision was not associated
with sedation requirements or patient discomfort scores. No adverse events were
reported from the use of the Endocuff Vision, although it was electively removed
in 6 patients where severe sigmoid colon diverticulosis was encountered and 2
patients because of discomfort during anal insertion. CONCLUSIONS: In this pilot
service evaluation study, the use of the Endocuff Vision appears to be associated
with an improvement in overall colonoscopy operator performance. We found
increased ADR and MAP as well as decreased time for colonoscope insertion and
withdrawal time with no increase in sedation requirements or patient discomfort.
PMID- 28412272
TI - Use of ceftolozane/tazobactam as salvage therapy for infections due to
extensively drug-resistant Pseudomonas aeruginosa.
PMID- 28412273
TI - Efficient inhibition of influenza A viral replication in cells by deoxyribozymes
delivered by nanocomposites.
AB - Nucleic-acid-based drugs are a promising class of novel therapeutics; however,
their use in medicine is widely limited because of insufficient delivery into
cells. This article proposes a new delivery strategy of nucleic acid fragments
into cells as components of TiO2-based nanocomposites. For the first time,
unmodified Dz molecules were non-covalently immobilized on TiO2 nanoparticles
precovered with polylysine (TiO2*PL) with the formation of (TiO2*PL)*Dz
nanocomposites. DNAzymes in the proposed nanocomposites were shown to retain
their ability to cleave the RNA target in a cell-free system with the same
selectivity as unbound Dz molecules. It was shown by confocal laser microscopy
that the fluorescein-labelled (TiO2*PL)*DzFlu nanocomposites penetrate into
eukaryotic cells, where DzFlu is internalized in the cytoplasm and predominantly
in nuclei. Delivery of deoxyribozymes into cells in the proposed nanocomposites
permits very efficient interactions with RNA targets inside cells. This was
demonstrated by an example of inhibition of H5N1 influenza A virus replication
(inhibition by a factor of ca. 3000). This effect was one order of magnitude
higher than with using lipofectamine as the transfection agent. The proposed
(TiO2*PL)*Dz nanocomposites demonstrated high antiviral activity and are thus
potent as nucleic-acid-based drugs.
PMID- 28412274
TI - Pharmacokinetics of linezolid in critically ill patients: impact of continuous
venovenous haemofiltration.
PMID- 28412276
TI - The influence of hypertension on daytime sleepiness in obstructive sleep apnea.
AB - Daytime sleepiness is a common symptom among hypertensive patients. The aim of
this study was to determine subjective sleepiness assessed by Epworth Sleepiness
Scale (ESS) and to asses sleep architecture in 304 patients with arterial
hypertension. All patients underwent a standardized diagnostic overnight,
polysomnography. The control group consisted of 67 normotensives. The
hypertensive patients had a decreased sleep efficiency, mean and minimum oxygen
saturation levels, and increased apnea/hypopnea index and oxygen desaturation
index compared with normotensive patients. The lower ratio of N3 sleep, higher of
N2 sleep, and decreased sleep efficiency was observed in hypertensives without
obstructive sleep apnea (OSA). In the moderate to severe OSA groups, the total
ESS score was significantly lower in hypertensives compared with normotensives.
The ESS scores decreased with age in hypertensives, but not in normotensives. The
study showed that ESS total score is lower in hypertensives than in normotensives
with OSA, making the OSA more difficult to suspect. Thus, the low ESS score in
hypertensives should not discourage further evaluation.
PMID- 28412275
TI - Achieving the BpTRUth: emergency department hypertension screening and the
Centers for Medicare & Medicaid Services quality measure.
AB - In 2012, the Centers for Medicare & Medicaid Services (CMS) instituted a
Physician Quality Reporting System measure for screening and referring patients
with elevated blood pressure (BP). The aims of this study were to (1) assess the
reliability of ED triage BP as a metric to establish when the CMS threshold
(>=120/80 mm Hg), and other clinically relevant BP thresholds (>=140/90 and
>=160/100 mm Hg) have been met, using BP measured with a highly accurate device
(BpTRU) in the emergency department as the gold standard; and (2) determine
whether correct identification varies by gender, race, or triage acuity. Using
the BpTRU, we calculated the proportion of patients whose triage BP accurately
indicated a need for further referral and treatment for hypertension according to
three suggested BP thresholds (>=120/80, >=140/90, and >=160/100 mm Hg). Of 354
patients, the median age was 39 years, 48.9% were women, and 66.4% were White. At
the three suggested BP thresholds (>=120/80, >=140/90, and >=160/100 mm Hg),
66.1%, 74.0%, and 88.8% of patients were confirmed to meet the CMS threshold,
respectively. There were no differences by gender, race, or triage acuity.
Emergency department triage BP would reliably identify elevated BP using the CMS
threshold in up to two-thirds of those without known hypertension.
PMID- 28412277
TI - The association of endothelial function and tone by digital arterial tonometry
with MRI left ventricular mass in African Americans: the Jackson Heart Study.
AB - Peripheral vascular endothelial dysfunction assessed by digital peripheral
arterial tonometry (PAT) has been associated with risk for adverse cardiovascular
events. We examined the relations of peripheral microvascular dysfunction and
left ventricular mass in a community-based cohort of African Americans. We
examined participants of the Jackson Heart Study who had PAT and cardiac magnetic
resonance imaging evaluations between 2007 and 2013. Consistent with pertinent
literature, left ventricular mass index (LVMI) was adjusted for body size by
indexing to height2.7. Pearson's correlation and general linear regression
analyses were used to relate reactive hyperemia index, baseline pulse amplitude
(BPA), and augmentation index (markers of microvascular vasodilator function,
baseline vascular pulsatility, and relative wave reflection, respectively) to
LVMI after adjusting for traditional cardiovascular risk factors. A total of 440
participants (mean age 59 +/- 10 years, 60% women) were included. Age- and sex
adjusted Pearson's correlation analysis suggested that natural log transformed
LVMI was negatively correlated with reactive hyperemia index (coefficient:
0.114; P = .02) and positively correlated with BPA (coefficient: 0.272; P <
.001). In multivariable analyses, higher loge LVMI was associated with higher BPA
(beta: 0.210; P = .03) after accounting for age, sex, body mass index, diabetes,
hypertension, ratio of total cholesterol and high-density lipoprotein
cholesterol, smoking, and history of cardiovascular disease. In a community-based
sample of African Americans, higher baseline pulsatility measured by PAT was
associated with higher LVMI by cardiac magnetic resonance imaging after adjusting
for traditional risk factors.
PMID- 28412278
TI - Disruption of glutamate neurotransmitter transmission is modulated by SNAP-25 in
benzo[a]pyrene-induced neurotoxic effects.
AB - Benzo[a]pyrene (B[a]P), a ubiquitous chemical contaminant in the environment, is
a well-established neurotoxicant to human. However, the molecular mechanisms for
B[a]P neurotoxicity are still unclear. In the present study, after treating
Sprague-Dawley rats with 0.02, 0.2 and 2.0mg/kg/day B[a]P for 7 weeks [from
postnatal day (PND) 5 to PND54], our results showed that B[a]P exposure caused a
significant deficits in learning and memory function. By using U87 cells as in
vitro model, the significant cytotoxicity and the induction of apoptosis caused
by B[a]P were further verified. More importantly, we demonstrated for the first
time that B[a]P exposure caused the disruption of glutamate (Glu)
neurotransmitter transmission by decreasing the level of Glu, reducing the
expression of Glu receptors (GluR1 and GluR2), enhancing the level of SNAP-25,
widening the synaptic cleft, and ultimately producing the neurotoxic effects in
both cells and animals. Our results will provide novel evidence to reveal the
possible role of SNAP-25 in B[a]P-induced neurotoxicity and may be helpful for
searching the potential strategy for the prevention measures against B[a]P
neurotoxicity.
PMID- 28412280
TI - Evaluation of sample preparation protocols for spider venom profiling by MALDI
TOF MS.
AB - Spider venoms are highly complex mixtures containing biologically active
substances with potential for use in biotechnology or pharmacology.
Fingerprinting of venoms by Matrix-Assisted Laser Desorption-Ionization - Time of
Flight Mass Spectrometry (MALDI-TOF MS) is a thriving technology, enabling the
rapid detection of peptide/protein components that can provide comparative
information. In this study, we evaluated the effects of sample preparation
procedures on MALDI-TOF mass spectral quality to establish a protocol providing
the most reliable analytical outputs. We adopted initial sample preparation
conditions from studies already published in this field. Three different MALDI
matrixes, three matrix solvents, two sample deposition methods, and different
acid concentrations were tested. As a model sample, venom from Brachypelma
albopilosa was used. The mass spectra were evaluated on the basis of absolute and
relative signal intensities, and signal resolution. By conducting three series of
analyses at three weekly intervals, the reproducibility of the mass spectra were
assessed as a crucial factor in the selection for optimum conditions. A sample
preparation protocol based on the use of an HCCA matrix dissolved in 50%
acetonitrile with 2.5% TFA deposited onto the target by the dried-droplet method
was found to provide the best results in terms of information yield and
repeatability. We propose that this protocol should be followed as a standard
procedure, enabling the comparative assessment of MALDI-TOF MS spider venom
fingerprints.
PMID- 28412279
TI - Cancer biology and Mr. Darwin.
PMID- 28412281
TI - Assessing the exploratory and anxiety-related behaviors of mice. Do different
caging systems affect the outcome of behavioral tests?
AB - Ample studies have shown that housing can affect the health, welfare and behavior
of mice and therefore, the outcomes of certain experiments. The aim of this study
was to investigate if three widely used housing systems, Open Top Cages (OTC),
Motor Free Ventilated Cages (MFVC) and Individually Ventilated Cages (IVC) may
affect exploratory and anxiety-related behaviors in mice. Subjects were 8week-old
male C57Bl/6J mice (n=36) divided into three groups, OTC, IVC and MFVC groups,
respectively. The experimental procedure consisted of two behavioral tests: the
open field and the elevated plus maze test. Although there were no differences in
the open field test, the results from the elevated plus maze showed that animals
housed in the MFVCs exhibited increased exploratory and less anxiety-like
behavior. It is concluded that the different caging systems may have an impact on
the outcome of behavioral tests used to assess exploratory and anxiety like
behavior in mice. Therefore, it is essential to take into consideration housing
conditions when reporting, analyzing, and/or systematically reviewing the results
of behavioral testing in mice.
PMID- 28412282
TI - Physiological reactivity to spontaneously occurring seizure activity in dogs with
epilepsy and their carers.
AB - There is a complex bidirectional relationship between stress and epilepsy.
Stressful stimuli and subsequent cortisol release act as a trigger for seizure
activity in some individuals with epilepsy, and seizure activity itself may act
as a stressor to the affected individual. Epilepsy is the most common chronic
neurological condition in domestic dogs and requires chronic management by their
human carers, impacting upon the quality of life of both dog and carer. Seizures
occur unpredictably and may be stressful for carers to witness and manage. In the
present study we investigated the role of seizure activity as a stressor,
measuring the effect of spontaneously occurring seizure activity in dogs with
epilepsy upon their own cortisol levels and that of their carers. Furthermore, we
tested whether individual differences in HPA reactivity were associated with
owner personality characteristics and the quality of the dog-carer relationship.
Saliva samples were obtained from sixteen dog-carer dyads in the home setting 20
and 40minute post-seizure, and at time-matched points on the following (non
seizure) day. Significant differences in cortisol levels were found in dogs at
40minute post-seizure (265.1% increase), and at 20minute post-seizure in their
carers (40.5% increase). No associations were found between cortisol reactivity
and the strength of the dog-carer bond. Carers with higher neuroticism scores
exhibited higher cortisol levels at both post-seizure sampling points. As there
was a gender bias in the carer sample (15/16 were female), and there are known
sex differences in cortisol reactivity in response to psychological stress, the
conclusions of this study may be limited to female carers. These findings are the
first to objectively demonstrate the acutely stressful effects of seizures in
dogs with epilepsy and their carers.
PMID- 28412283
TI - Complement factor C4 activation in patients with hereditary angioedema.
AB - OBJECTIVES: Low complement factor C4 is usually considered a valuable screening
tool for patients with the potentially life-threatening hereditary angioedema
with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients
with C1-INH-HAE presenting with normal C4 levels. This means, that C1-INH-HAE may
potentially be overlooked, if screening is performed only by measurement of C4.
It has been suggested that measurement of C4 activation products is better suited
to avoid false negative results. Our aim was to investigate whether total
antigenic C4 or non-functional C4c is a better measure of the increased C4
activation in C1-INH-HAE patients. DESIGN AND METHODS: Two different monoclonal
antibodies (mAb) to human C4 were produced: one had specificity for the beta
chain of C4 and would thus react with both functional and non-functional C4, and
the other was developed against the factor I cleavage site on the alpha3-domain
of C4 and was thus specific for activated, non-functional C4c. With these mAb we
investigated plasma from 19 Danish C1-INH-HAE patients in three different enzyme
linked immunosorbent assays (ELISAs): a total antigenic C4 assay, a functional C4
assay and an assay measuring non-functional C4c. RESULTS: The amount of total
antigenic C4 varied considerably between patients and 2 patients had total
antigenic C4 levels in the normal area. Functional C4 was low in all C1-INH-HAE
patients. A C4c/C4 ratio showed that around half the C4 measured in patients was
non-functional and captured all C1-INH-HAE patients. CONCLUSIONS: This study
shows that the C4c/C4 ratio seems to be a better diagnostic measure than total
antigenic C4 alone. Our findings underline that screening with total antigenic C4
implies a risk of overlooking C1-INH-HAE patients.
PMID- 28412284
TI - Effects of preanalytical factors on hemoglobin measurement: A comparison of two
HemoCue(r) point-of-care analyzers.
AB - BACKGROUND: In field studies, hemoglobin (Hb) is often measured using a battery
operated, portable HemoCue(r) hemoglobinometer. METHODS: We compared the
performance of 2 HemoCue(r) models (Hb-201+ and Hb-301) and investigated effects
of preanalytical factors on Hb results by simulating unfavorable field
conditions. RESULTS: The Hb-301 produced 2.6% higher results compared to the Hb
201+. Hb had to be measured within 1min of filling the Hb-301 cuvette to avoid
artificially elevated concentrations (1.3% per min). The Hb-301 cuvettes
withstood elevated temperature (37 degrees C) and humidity (72%) for 3weeks,
while the Hb-201+ cuvettes degraded within 10min under those conditions. Both
cuvette types withstood elevated temperature for 3weeks. Properly-collected
venous and capillary blood produced comparable results. Pooled capillary blood
produced comparable results to the second and third but not the fourth drop of
blood (3.3% lower). Blood could be stored for <=4days at 10-30 degrees C before
Hb-201+ measurement, but only for 1day at 10-23 degrees C before Hb-301
measurement (<=1% change in Hb). CONCLUSIONS: Higher Hb results obtained with the
Hb-301 may influence the interpretation of anemia prevalence in health surveys.
While the Hb-301 performed better in high humidity conditions, the Hb-201+
provided more user flexibility regarding delayed Hb reading.
PMID- 28412285
TI - Middle East respiratory syndrome coronavirus vaccines: current status and novel
approaches.
AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe
respiratory infection in humans, specifically the elderly and people with
comorbidities. The re-emergence of lethal coronaviruses calls for international
collaboration to produce coronavirus vaccines, which are still lacking to date.
Ongoing efforts to develop MERS-CoV vaccines should consider the different target
populations (dromedary camels and humans) and the correlates of protection.
Extending on our current knowledge of MERS, vaccination of dromedary camels to
induce mucosal immunity could be a promising approach to diminish MERS-CoV
transmission to humans. In addition, it is equally important to develop vaccines
for humans that induce broader reactivity against various coronaviruses to be
prepared for a potential next CoV outbreak.
PMID- 28412286
TI - Beneficial effects of glutathione supplementation during vitrification of mouse
oocytes at the germinal vesicle stage on their preimplantation development
following maturation and fertilization in vitro.
AB - Oocyte cryopreservation is imperative for assisted reproductive technologies
(ART). Although cryopreservation of oocytes at the Metaphase II has been widely
used, immature oocytes at the germinal vesicle stage (GV-oocytes) need to be
cryopreserved in certain situations such as cancer patients; however, the success
rate of embryonic development from the GV-oocytes remains low largely due to the
requirement for in vitro maturation (IVM). Our aim was to investigate the effects
of glutathione (GSH) supplementation during vitrification and warming of mouse GV
oocytes on the preservation of developmental competence. GV-oocytes within
cumulus oocyte complexes (COCs) were collected from C57BL/6J (B6) and (B6.DBA)F1
mouse strains and subjected to vitrification and warming, followed by IVM. The
vitrification, warming or IVM medium was supplemented with GSH at 0-4.0 mM. In
vitro matured oocytes were then fertilized in vitro and cultured in KSOMaa up to
4 days. The first cleavage and blastocyst development were evaluated
morphologically, and their rates were statistically analysed by one-way ANOVA
followed by Tukey's multiple comparisons test. The difference was considered
significant at P < 0.05. The results showed that GSH supplementation in the IVM
medium exhibited no or rather inhibitory effects on the first cleavage or
blastocyst development in both mouse strains except that 1.0 mM GSH increased the
blastocyst development rate in B6. By contrast, 1 mM GSH supplementation during
vitrification and warming increased the blastocyst development rate in both mouse
strains, more efficiently in B6 than (B6.DBA)F1. In conclusion, GSH
supplementation during vitrification and warming of GV-oocytes protects the
oocytes from freezing-inflicted loss of developmental competence.
PMID- 28412288
TI - Adult T-type lymphoblastic lymphoma: Treatment advances and prognostic
indicators.
AB - T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor
T cells that occurs mostly in adolescents and young adults. In this review, we
describe the treatment of adult T-LBL with a focus on recent advances using
pediatric-inspired acute lymphoblastic leukemia regimens, which have greatly
improved outcome. We also discuss the development of prognostic indicators for T
LBL, especially oncogenetic factors, that can identify patients at higher risk of
relapse and may help further extend T-LBL patient survival. Pediatric-inspired
acute lymphoblastic leukemia regimens have the potential to become the treatment
of choice for adult T-LBL, and they might also reduce the need for other
longstanding T-LBL interventions, particularly mediastinal irradiation and stem
cell transplantation.
PMID- 28412287
TI - Changes in rat respiratory system produced by exposure to exhaust gases of
combustion of glycerol.
AB - The combustion of residual glycerol to generate heat in industrial processes has
been suggested as a cost-effective solution for disposal of this environmental
liability. Thus, we investigated the effects of exposure to the exhaust gases of
glycerol combustion in the rat respiratory system. We used 2 rats groups, one
exposed to the exhaust gases from glycerol combustion (Glycerol), and the other
exposed to ambient air (Control). Exposure occurred 5h a day, 5days a week for 13
weeks. We observed statistically changes in all parameters of respiratory system
mechanics in vivo. This results was supported by histological analysis and
morphometric data, confirming narrower airways and lung parenchimal changes.
Variables related to airway resistance (DeltaRN) and elastic properties of the
tissue (DeltaH), increased after challenge with methacholine. Finally, analysis
of lung tissue micromechanics showed statistically increases in all parameters
(R, E and hysteresivity). In conclusion, exhaust gases from glycerol combustion
were harmful to the respiratory system.
PMID- 28412291
TI - Reply to: "Negotiating better discounts for DAA therapy is critical to achieve
HCV elimination by 2030".
PMID- 28412290
TI - Lack of decline in hepatitis C virus incidence among HIV-positive men who have
sex with men during 1990-2014.
AB - BACKGROUND & AIMS: Hepatitis C virus (HCV) incidence among HIV-positive men who
have sex with men (MSM) has increased since 2000, although there are regional
differences. We aimed to 1) estimate trends in HCV incidence among HIV-positive
MSM, 2) assess the association between incidence and geographical region, age and
HIV-related measurements and, 3) assess temporal changes from HIV seroconversion
to HCV infection. METHODS: Data was used from MSM with well-estimated dates of
HIV seroconversion from the CASCADE Collaboration (1990-2014). Smoothly varying
trends in HCV incidence over time were allowed, using restricted cubic splines.
The association of calendar year, age, CD4 count (lagged), HIV RNA (lagged),
geographical region and HIV infection stage (recent vs. chronic) with HCV
incidence were assessed using Poisson regression. RESULTS: Of 5,941 MSM, 337
acquired HCV during follow-up. HCV incidence significantly increased from
0.7/1,000 person-years in 1990 to 18/1,000 person-years in 2014. Recent calendar
years, younger age, recent HIV infection and higher HIV RNA levels were
significantly associated with HCV incidence, while CD4 count was not. Trends
differed by geographical region; while incidence appeared to have stabilized in
Western Europe and remained stable in Southern Europe, it continued to increase
in Northern Europe in recent years. Time from HIV to HCV infection significantly
decreased over time (p<0.001). CONCLUSIONS: HCV has continued to spread among HIV
positive MSM in recent years, but trends differ by geographical region.
Interventions to decrease the risk of HCV acquisition and increase early
diagnosis are warranted. LAY SUMMARY: Hepatitis C virus infection continues to
spread among HIV-positive men who have sex with men, especially among younger
individuals. However, trends seem to differ by European region in recent years.
Furthermore, men who have sex with men with a higher HIV RNA load were more
likely to get infected with the hepatitis C virus. During recent HIV infection,
MSM appear to be at higher risk of acquiring hepatitis C.
PMID- 28412289
TI - Structural studies of the endogenous spliceosome - The supraspliceosome.
AB - Pre-mRNA splicing is executed in mammalian cell nuclei within a huge (21MDa) and
highly dynamic molecular machine - the supraspliceosome - that individually
package pre-mRNA transcripts of different sizes and number of introns into
complexes of a unique structure, indicating their universal nature. Detailed
structural analysis of this huge and complex structure requires a stepwise
approach using hybrid methods. Structural studies of the supraspliceosome by room
temperature electron tomography, cryo-electron tomography, and scanning
transmission electron microscope mass measurements revealed that it is composed
of four native spliceosomes, each resembling an in vitro assembled spliceosome,
which are connected by the pre-mRNA. It also elucidated the arrangement of the
native spliceosomes within the intact supraspliceosome. Native spliceosomes and
supraspliceosomes contain all five spliceosomal U snRNPs together with other
splicing factors, and are active in splicing. The structure of the native
spliceosome, at a resolution of 20A, was determined by cryo-electron microscopy,
and a unique spatial arrangement of the spliceosomal U snRNPs within the native
spliceosome emerged from in silico studies. The supraspliceosome also harbor
components for all pre-mRNA processing activities. Thus the supraspliceosome -
the endogenous spliceosome - is a stand-alone complete macromolecular machine
capable of performing splicing, alternative splicing, and encompass all nuclear
pre-mRNA processing activities that the pre-mRNA has to undergo before it can
exit from the nucleus to the cytoplasm to encode for protein. Further high
resolution cryo-electron microscopy studies of the endogenous spliceosome are
required to decipher the regulation of alternative splicing, and elucidate the
network of processing activities within it.
PMID- 28412292
TI - HLA-Bw4 80(T) and multiple HLA-Bw4 copies combined with KIR3DL1 associate with
spontaneous clearance of HCV infection in people who inject drugs.
AB - BACKGROUND & AIMS: Natural killer (NK) cell function is regulated by inhibitory
and activating receptors including killer cell immunoglobulin-like receptors
(KIRs). Here, we analyzed the impact of different KIR/KIR-ligand genotypes on the
outcome of hepatitis C virus (HCV) infection in people who inject drugs (PWID).
METHODS: KIR/KIR-ligand genotypes associated with spontaneous clearance of HCV
infection were identified in a cohort of PWID from Germany (n=266) and further
validated in a second anti-HCV positive cohort of PWID recruited in North America
(n=342). NK cells of PWID and healthy donors were functionally characterized
according to their KIR/KIR-ligand genotype by flow cytometry. RESULTS:
Multivariate logistic regression analysis revealed that KIR3DL1/HLA-Bw4 80(T) was
associated with spontaneous clearance of HCV infection in PWID, which was
confirmed in the PWID cohort from North America. Compared with PWID with
detectable HCV RNA, the frequency of individuals with multiple HLA-Bw4 alleles
was significantly higher in anti-HCV positive PWID with resolved HCV infection
(29.7% vs. 15.2%; p=0.0229) and in anti-HCV seronegative PWID (39.2%; p=0.0006).
KIR3DL1+ NK cells from HLA-Bw4 80(T)-positive PWID showed superior functionality
compared to HLA-Bw4 80(I)-positive PWID. This differential impact was not
observed in healthy donors; however, the HLA-Bw4 copy number strongly correlated
with the functionality of KIR3DL1+ NK cells. CONCLUSIONS: HLA-Bw4-80(T) and
multiple HLA-Bw4 copies in combination with KIR3DL1 are associated with
protection against chronic hepatitis C in PWID by distinct mechanisms. Better
licensing of KIR3DL1+ NK cells in the presence of multiple HLA-Bw4 copies is
beneficial prior to seroconversion whereas HLA-Bw4 80(T) may be beneficial during
acute hepatitis C. Lay summary: Natural killer (NK) cells are part of the innate
immune system and are regulated by a complex network of activating and inhibiting
receptors. The regulating receptor-ligand pairs of an individual are genetically
determined. Here, we identified a particular set of ligand and receptor genes
that are associated with better functionality of NK cells and better outcome upon
exposure to HCV in a high-risk group.
PMID- 28412293
TI - Glecaprevir and pibrentasvir yield high response rates in patients with HCV
genotype 1-6 without cirrhosis.
AB - BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy that is highly efficacious,
pangenotypic, with a high barrier to resistance and short treatment duration is
desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir
(ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor)
were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.
METHODS: SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose
ranging trials including patients with chronic HCV genotype 1-6 infection who
were either previously untreated or treated with pegylated interferon plus
ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying
doses with or without ribavirin for 8 or 12weeks. The primary efficacy endpoint
was the percentage of patients with a sustained virologic response at post
treatment week 12 (SVR12). RESULTS: Of the 449 patients who received varying
doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1,
2, 3, and 4-6 infection, respectively. Twelve-week treatment achieved SVR12 in 97
100%, 96-100%, 83-94%, and 100% in genotypes 1, 2, 3, and 4-6, respectively.
Eight-week treatment with 300mg glecaprevir plus 120mg pibrentasvir in genotype 1
, 2-, or 3-infected patients yielded 97-98% SVR12 with no virologic failures.
Three (0.7%) patients discontinued treatment due to adverse events; most events
were mild (grade 1) in severity. No post-nadir alanine aminotransferase
elevations were observed. CONCLUSIONS: Glecaprevir plus pibrentasvir was well
tolerated and achieved high sustained virologic response rates in HCV genotypes 1
6-infected patients without cirrhosis following 8- or 12-week treatment
durations. LAY SUMMARY: The combination of direct-acting antivirals glecaprevir
and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV
genotype 1-6 infection. This article describes results from two phase II trials
investigating a range of doses at treatment durations of 8 or 12weeks in 449
patients without cirrhosis. Efficacy of the optimal dose, as determined by rates
of sustained virologic response at post-treatment week 12, ranged from 92%-100%;
treatment was well tolerated and significant laboratory abnormalities were rare.
CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT02243280 and
NCT02243293. http://www.clinicaltrials.gov/show/NCT02243280,
http://www.clinicaltrials.gov/show/NCT01939197.
PMID- 28412294
TI - Visualization of hepatitis E virus RNA and proteins in the human liver.
AB - BACKGROUND & AIMS: Although hepatitis E constitutes a substantial disease burden
worldwide, surprisingly little is known about the localization of hepatitis E
virus (HEV) in the human liver. We therefore aimed to visualize HEV RNA and
proteins in situ. METHODS: A panel of 12 different antibodies against HEV open
reading frame (ORF) 1-3 proteins was evaluated for immunohistochemistry (IHC) and
two probes for in situ hybridization (ISH) in formalin-fixed, paraffin-embedded
(FFPE) HuH7 cells transfected with HEV ORF1-3 expression vectors. IHC (and partly
ISH) were then applied to Hep293TT cells replicating infectious HEV and liver
specimens from patients with hepatitis E (n=20) and controls (n=134). RESULTS:
Whereas ORF1-3 proteins were all detectable in transfected, HEV protein
expressing cells, only ORF2 and 3 proteins were traceable in cells replicating
infectious HEV. Only the ORF2-encoded capsid protein was also unequivocally
detectable in liver specimens from patients with hepatitis E. IHC for ORF2
protein revealed a patchy expression in individual or grouped hepatocytes,
generally stronger in chronic compared to acute hepatitis. Besides cytoplasmic
and canalicular, ORF2 protein also displayed a hitherto unknown nuclear
localization. Positivity for ORF2 protein in defined areas correlated with HEV
RNA detection by ISH. IHC was specific and comparably sensitive as PCR for HEV
RNA. CONCLUSIONS: ORF2 protein can be reliably visualized in the liver of
patients with hepatitis E, allowing for sensitive and specific detection of HEV
in FFPE samples. Its variable subcellular distribution in individual hepatocytes
of the same liver suggests a redistribution of ORF2 protein during infection and
interaction with nuclear components. LAY SUMMARY: The open reading frame (ORF) 2
protein can be used to visualize the hepatitis E virus (HEV) in the human liver.
This enabled us to discover a hitherto unknown localization of the HEV ORF2
protein in the nucleus of hepatocytes and to develop a test for rapid
histopathologic diagnosis of hepatitis E, the most common cause of acute
hepatitis worldwide.
PMID- 28412295
TI - Evidence for a role of genetics in alcoholic hepatitis: Data from the STOPAH
randomized controlled trial.
PMID- 28412297
TI - Dysferlinopathy Promotes an Intramuscle Expansion of Macrophages with a Cyto
Destructive Phenotype.
AB - Dysferlinopathies are a group of muscular dystrophies resulting from a genetic
deficiency in Dysf. Macrophages, highly plastic cells that mediate tissue repair
and destruction, are prominent within dystrophic skeletal muscles of
dysferlinopathy patients. We hypothesized that Dysf-deficient muscle promotes
recruitment, proliferation, and skewing of macrophages toward a cyto-destructive
phenotype in dysferlinopathy. To track macrophage dynamics in dysferlinopathy, we
adoptively transferred enhanced green fluorescent protein-labeled monocytes into
Dysf-deficient BLA/J mice with age-related (2 to 10 months) muscle disease and
Dysf-intact (C57BL/6 [B6]) mice. We detected an age- and disease-related increase
in monocyte recruitment into Dysf-deficient muscles. Moreover, macrophages
recruited into muscle proliferated locally and were skewed toward a cyto
destructive phenotype. By comparing Dysf-deficient and -intact monocytes, our
data showed that Dysf in muscle, but not in macrophages, mediate intramuscle
macrophage recruitment and proliferation. To further elucidate macrophage
mechanisms related to dysferlinopathy, we investigated in vitro macrophage
myogenic cell interactions and found that Dysf-deficient muscle i) promotes
macrophage proliferation, ii) skews macrophages toward a cyto-destructive
phenotype, and iii) is more vulnerable to macrophage-mediated apoptosis. Taken
together, our data suggest that the loss of Dysf expression in muscle, not
macrophages, promotes the intramuscle expansion of cyto-destructive macrophages
likely to contribute to dysferlinopathy. Identifying pathways within the Dysf
deficient muscle milieu that regulate cyto-destructive macrophages will
potentially uncover therapeutic strategies for dysferlinopathies.
PMID- 28412296
TI - Impact of higher-order heme degradation products on hepatic function and
hemodynamics.
AB - BACKGROUND & AIMS: Biliverdin and bilirubin were previously considered end
products of heme catabolism; now, however, there is evidence for further
degradation to diverse bioactive products. Z-BOX A and Z-BOX B arise upon
oxidation with unknown implications for hepatocellular function and integrity. We
studied the impact of Z-BOX A and B on hepatic functions and explored their
alterations in health and cholestatic conditions. METHODS: Functional
implications and mechanisms were investigated in rats, hepatocytic HepG2 and
HepaRG cells, human immortalized hepatocytes, and isolated perfused livers. Z-BOX
A and B were determined by liquid chromatography-tandem mass spectrometry (LC
MS/MS) in acute and acute-on-chronic liver failure and hereditary unconjugated
hyperbilirubinemia. RESULTS: Z-BOX A and B are found in similar amounts in humans
and rodents under physiological conditions. Serum concentrations increased ~20
fold during cholestatic liver failure in humans (p<0.001) and in hereditary
deficiency of bilirubin glucuronidation in rats (p<0.001). Pharmacokinetic
studies revealed shorter serum half-life of Z-BOX A compared to its regio-isomer
Z-BOX B (p=0.035). While both compounds were taken up by hepatocytes, Z-BOX A was
enriched ~100-fold and excreted in bile. Despite their reported vasoconstrictive
properties in the brain vasculature, BOXes did not affect portal hemodynamics.
Both Z-BOX A and B showed dose-dependent cytotoxicity, affected the glutathione
redox state, and differentially modulated activity of Rev-erbalpha and Rev
erbbeta. Moreover, BOXes-triggered remodeling of the hepatocellular cytoskeleton.
CONCLUSIONS: Our data provide evidence that higher-order heme degradation
products, namely Z-BOX A and B, impair hepatocellular integrity and might mediate
intra- and extrahepatic cytotoxic effects previously attributed to
hyperbilirubinemia. LAY SUMMARY: Degradation of the blood pigment heme yields the
bile pigment bilirubin and the oxidation products Z-BOX A and Z-BOX B. Serum
concentrations of these bioactive molecules increase in jaundice and can impair
liver function and integrity. Amounts of Z-BOX A and Z-BOX B that are observed
during liver failure in humans have profound effects on hepatic function when
added to cultured liver cells or infused into healthy rats.
PMID- 28412298
TI - Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound
Healing.
AB - Tight junction (TJ) proteins are known to be involved in proliferation and
differentiation. These processes are essential for normal skin wound healing.
Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin
wound healing models and tissue samples of acute and chronic human wounds and
observed major differences in localization/expression of these proteins, with
chronic wounds often showing a loss of the proteins at the wound margins and/or
in the regenerating epidermis. Knockdown experiments in primary human
keratinocytes showed that decreased claudin-1 expression resulted in
significantly impaired scratch wound healing, with delayed migration and reduced
proliferation. Activation of AKT pathway was significantly attenuated after
claudin-1 knockdown, and protein levels of extracellular signal-related kinase
1/2 were reduced. For occludin, down-regulation had no impact on wound healing in
normal scratch assays, but after subjecting the cells to mechanical stress, which
is normally present in wounds, wound healing was impaired. For both proteins we
show that most of these actions are independent from the formation of barrier
forming TJ structures, thus demonstrating nonbarrier-related functions of TJ
proteins in the skin. However, for claudin-1 effects on scratch wound healing
were more pronounced when TJs could form. Together, our findings provide evidence
for a role of claudin-1 and occludin in epidermal regeneration with potential
clinical importance.
PMID- 28412299
TI - Toll-Like Receptor 4-Independent Carbon Tetrachloride-Induced Fibrosis and
Lipopolysaccharide-Induced Acute Liver Injury in Mice: Role of Hepatic Stellate
Cells.
AB - Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is implicated in acute
and chronic liver injury; its effects are mediated predominantly via the membrane
receptor Toll-like receptor 4 (TLR4). However, TLR4-independent effects of LPS
may play important role in hepatic pathophysiology. We investigated carbon
tetrachloride (CCl4)-induced fibrosis and LPS-induced acute liver injury in wild
type (WT) and B6.B10ScN-Tlr4lps-del/JthJ [TLR4-knockout (KO)] mice. Effects of
LPS on fibrogenic hepatic stellate cells (HSCs) from WT and TLR4-KO mice were
assessed in vitro. CCl4 produced similar fibrosis and necroinflammation and
increased the mRNA and protein expression of cytokines and chemokines in WT and
TLR4-KO mice. However, circulating LPS concentration did not increase in CCl4
treated mice. Interestingly, LPS down-modulated alpha-smooth muscle actin
(activated HSC marker) and collagen 1 in both WT and TLR4-KO HSCs. LPS induced
similar activation of NF-kappaB, and stimulated the expression of cytokines and
chemokines in WT and TLR4-KO HSCs. Finally, LPS caused similar inflammation and
injury in previously untreated WT and TLR4-KO mice. The results provide evidence
of the TLR4/LPS-independent mechanisms of liver fibrosis and also indicate that
TLR4 is not entirely critical to LPS-induced acute liver injury. The results
further indicate that LPS signaling in activated HSCs might be a mechanism of
limiting liver fibrosis.
PMID- 28412301
TI - Environmental risks outweigh dopaminergic genetic risks for alcohol use and abuse
from adolescence through early adulthood.
AB - BACKGROUND: Alcohol use is a primary public health concern, particularly among
adolescents and young adults. Based on the rapidly growing field of gene
environment models, this study assessed the combined role of environmental and
dopamine-related genetic correlates of early alcohol use and abuse. METHODS:
Multilevel growth models assessed trajectories of alcohol use and intoxication
and ordered logistic regressions assessed alcohol use disorder among a sample of
12,437 youth from the nationally representative Add Health study who were
followed from mid-adolescence through early adulthood. RESULTS: Endogenous and
exogenous stressful life events and social norms supportive of alcohol use from
parents and peers were significant predictors of alcohol use, intoxication, and
alcohol use disorder, with consistent patterns across males and females. In
contrast, a dopamine-system genetic risk score (GRS) was not associated with
alcohol use trajectories nor alcohol use disorder in early adulthood, although
weak connections emerged between the GRS and growth trajectories of intoxication,
indicating that higher GRS predicted more frequent episodes of intoxication
during the transition to adulthood but not during adolescence or later 20s. No
evidence of gene-environment interactions emerged. CONCLUSIONS: Results extend a
substantial body of prior research primarily assessing single genetic
polymorphisms in the dopamine system, suggesting that dopaminergic GRSs may be
associated with more problematic alcohol behaviors at some developmental periods,
but further, that social norms and stressful life experiences are more consistent
correlates of early and problematic alcohol use among youth. These environmental
factors present potential targets for research manipulating contexts to identify
causal pathways.
PMID- 28412300
TI - Mechanisms of Retinal Damage after Ocular Alkali Burns.
AB - Alkali burns to the eye constitute a leading cause of worldwide blindness. In
recent case series, corneal transplantation revealed unexpected damage to the
retina and optic nerve in chemically burned eyes. We investigated the physical,
biochemical, and immunological components of retinal injury after alkali burn and
explored a novel neuroprotective regimen suitable for prompt administration in
emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction
measurements were performed in the anterior and posterior segment of mouse and
rabbit eyes using implantable microsensors. Tissue inflammation was assessed by
immunohistochemistry and flow cytometry. The experiments confirmed that the
retinal damage is not mediated by direct effect of the alkali, which is
effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation
reduction changes were restricted to the cornea and the anterior chamber, where
they caused profound uveal inflammation and release of proinflammatory cytokines.
The latter rapidly diffuse to the posterior segment, triggering retinal damage.
Tumor necrosis factor-alpha was identified as a key proinflammatory mediator of
retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor
necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion
cell loss. Intraocular pressure elevation was not observed in experimental alkali
burns. These findings illuminate the mechanism by which alkali burns cause
retinal damage and may have importance in designing therapies for retinal
protection.
PMID- 28412302
TI - Who benefits from computer-based brief alcohol intervention? Day-to-day drinking
patterns as a moderator of intervention efficacy.
AB - OBJECTIVE: to test if people with different day-to-day drinking patterns
benefitted differently from two brief alcohol interventions (BAIs). METHODS: A
total of 1243 job-seekers with at-risk alcohol use aged 18-64 years (64% men)
were randomized to (a) intervention tailored to the motivational stage (ST), (b)
non-stage tailored intervention (NST), or (c) assessment only (AO). ST and NST
contained individualized computer-generated feedback letters. Follow-ups were
conducted at months 3, 6, and 15. Using growth mixture models, day-to-day
drinking patterns were identified based on the number of drinks consumed on each
day in the week prior to baseline assessment. To test drinking pattern-specific
intervention effects, zero-inflated growth models were used. Outcomes were (1)
the 15-month change in the likelihood of any alcohol use and (2) the 15-month
change in the total number of drinks per week when alcohol was consumed. RESULTS:
Four day-to-day drinking patterns were found: daily medium use (2-4 drinks/day;
47%), daily low use (1-2 drinks/day; 29%), weekend only use (18%), and no use
(6%). Only persons with daily low use benefitted from intervention, with higher
odds of being abstinent after 15 months in the ST group compared to AO (odds
ratio, OR=1.67, p=0.001) and NST group (OR=1.43, p=0.035). ST worked better among
persons with daily low use compared to daily medium use (OR=1.91, p=0.001).
CONCLUSIONS: Among at-risk drinking persons with regular low-quantity alcohol
use, stage tailored BAIs may be superior over no BAI and non-stage tailored BAIs.
PMID- 28412303
TI - Laboratory analysis of risky driving at 0.05% and 0.08% blood alcohol
concentration.
AB - BACKGROUND: The public health costs associated with alcohol-related traffic
crashes are a continuing problem for society. One harm reduction strategy has
been to employ per se limits for blood alcohol concentrations (BACs) at which
drivers can legally operate motor vehicles. This limit is currently 0.08% in all
50 US states. Recently, the National Transportation Safety Board proposed
lowering the legal limit to 0.05% (NTSB, 2013). While research has well-validated
the ability of alcohol to impair driving performance and heighten crash-risk at
these BACs, relatively little is known about the degree to which alcohol might
increase drivers' risk-taking. METHODS: Risk-taking was examined in 20 healthy
adults who were each tested in a driving simulator following placebo and two
doses of alcohol calculated to yield peak BACs of 0.08% and 0.05%, the respective
current and proposed BAC limits. The drive test emphasized risk-taking by placing
participants in a multiple-lane, high-traffic environment. The primary measure
was how close drivers maneuvered relative to other vehicles on the road (i.e.,
time-to-collision, TTC). RESULTS: Alcohol increased risk-taking by decreasing
drivers' TTC at the 0.08% target BAC relative to placebo. Moreover, risk-taking
at the 0.05% target was less than risk-taking at 0.08% target BAC. CONCLUSIONS:
These findings provide evidence that reducing the legal BAC limit in the USA to
0.05% would decrease risk-taking among drivers. A clearer understanding of the
dose-response relationship between various aspects of driving behaviors, such as
drivers' accepted level of risk while driving, is an important step to improving
traffic safety.
PMID- 28412304
TI - Synergistic effect between D-AP5 and muscimol in the nucleus accumbens shell on
memory consolidation deficit in adult male Wistar rats: An isobologram analysis.
AB - The nucleus accumbens (NAc) glutamatergic and GABAergic systems are involved in
memory processes. This study was investigated the involvement of NAc shell
GABAergic system on D-AP5 induced memory consolidation deficit. The elevated plus
maze (EPM) test-retest paradigm was employed to assess memory in adult male
Wistar rats. The results indicated that post-training intra-NAc shell injection
of bicuculline (GABAA receptor antagonist) did not alter emotional memory
consolidation. However, post-training intra-NAc shell microinjection of muscimol
(GABAA receptor agonist, 0.1MUg/rat) and D-AP5 (a competitive NMDA receptor
antagonist, 4MUg/rat) decreased emotional memory consolidation, suggesting the
drugs induced amnesia. Moreover, a sub-threshold dose of muscimol (0.05MUg/rat)
potentiated the D-AP5 (2MUg/rat) response on memory consolidation impairment. On
the other hand, the middle dose of bicuculline (0.25MUg/rat) reversed memory
impairment induced by D-AP5 at the higher dose. Interestingly, there is a
synergistic effect between D-AP5 and muscimol on impairment of emotional memory
consolidation. None of the above doses changed the locomotor activity. Our
results suggest that the glutamatergic and GABAergic neurons of the NAc shell
interact with each other for modulation of emotional memory consolidation.
PMID- 28412306
TI - Time-dependent sensitization of antipsychotic effect in adolescent male and
female rats.
AB - Many behavioral and biological effects of a psychoactive drug often undergo time
dependent change following even one single drug exposure. The present study
examined whether one or two exposures of haloperidol, olanzapine or clozapine
would also induce a time-dependent change in their behavioral effects in
adolescent rats, and whether such a change vary between sexes. Adolescent Sprague
Dawley rats (<40days old) were first treated with one single injection of
haloperidol (0.05 and 0.1mg/kg, sc), clozapine (10.0 and 20.0mg/kg, sc), 2
injections of olanzapine (1.0 and 2.0mg/kg, sc) or vehicle, and tested in a
conditioned avoidance response (CAR) model or a PCP (3.20mg/kg, sc)-induced
hyperlocomotion model to assess the drug's antipsychotic-like behavioral effects.
One or three weeks later, rats were challenged with the drug and their avoidance
responses and the PCP-induced hyperlocomotion were re-assessed. One-trial
haloperidol and 2-trial olanzapine induced a sensitization, while 1-trial
clozapine induced a tolerance effect. The 1-trial haloperidol sensitization was
significantly higher at the 3-week time point than at 1-week point, especially in
the females. Clozapine tolerance in the conditioned avoidance response model also
exhibited the time-dependent increase in both sex groups. Olanzapine
sensitization in the PCP model showed a time-dependent change in a sex-dependent
fashion. Overall, the time-dependent antipsychotic sensitization and tolerance
can be demonstrated in adolescent animals. Many pharmacological (e.g. specific
drugs, drug doses), individual (e.g. male versus female) and environmental (e.g.
specific behavioral models) factors play a role in the modulation of the strength
of antipsychotic sensitization and tolerance.
PMID- 28412305
TI - Memantine improves outcomes after repetitive traumatic brain injury.
AB - Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is
common and results in significant cognitive impairment. Targeted therapies for
rmTBI are lacking, though evidence from other injury models indicates that
targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic
toxicity might mitigate rmTBI-induced neurologic deficits. However, there is a
paucity of preclinical or clinical data regarding NMDAR antagonist efficacy in
the rmTBI setting. To test whether NMDAR antagonist therapy improves outcomes
after rmTBI, mice were subjected to rmTBI injury (4 injuries in 4days) and
randomized to treatment with the NMDA antagonist memantine or with vehicle.
Functional outcomes were assessed by motor, anxiety/impulsivity and mnemonic
behavioral tests. At the synaptic level, NMDAR-dependent long-term potentiation
(LTP) was assessed in isolated neocortical slices. At the molecular level, the
magnitude of gliosis and tau hyper-phosphorylation was tested by Western blot and
immunostaining, and NMDAR subunit expression was evaluated by Western blot and
polymerase chain reaction (PCR). Compared to vehicle-treated mice, memantine
treated mice had reduced tau phosphorylation at acute time points after injury,
and less glial activation and LTP deficit 1 month after injury. Treatment with
memantine also corresponded to normal NMDAR expression after rmTBI. No
corresponding protection in behavior outcomes was observed. Here we found NMDAR
antagonist therapy may improve histopathological and functional outcomes after
rmTBI, though without consistent corresponding improvement in behavioral
outcomes. These data raise prospects for therapeutic post-concussive NMDAR
antagonism, particularly in athletes and warriors, who suffer functional
impairment and neurodegenerative sequelae after multiple concussions.
PMID- 28412307
TI - The 9th Conference on Metal Toxicity and Carcinogenesis: The conference overview.
AB - Heavy metals, such as arsenic, chromium, cadmium, nickel, mercury, and uranium
are known to cause many human diseases and health complications after
occupational or environmental exposure. Consequently, metals are environmental
health concerns. This manuscript is an overview of the 9th Conference on Metal
Toxicity and Carcinogenesis held in October 2016 in Lexington, Kentucky. Since
2000, this biennial meeting brings together experts in the field to discuss
current and prospective research in an effort to advance research pertaining to
metal toxicity and carcinogenesis. In this review we summarize the major topics
discussed and provide insight regarding current research in the field and an
account of the direction in which the field is progressing.
PMID- 28412308
TI - Genistein prevention of hyperglycemia and improvement of glucose tolerance in
adult non-obese diabetic mice are associated with alterations of gut microbiome
and immune homeostasis.
AB - Although studies have linked soy phytoestrogen 4,7,4-trihydroxyisoflavone
genistein (GEN) to reduced type 1 diabetes (T1D) risk, the mechanism of dietary
GEN on T1D remains unknown. In our studies, adult non-obese diabetic (NOD) mouse
model was employed to investigate the effects of GEN exposure on blood glucose
level (BGL), glucose tolerance, gut microbiome, and immune responses. Adult male
and female NOD mice were fed with either soy-based or casein-based diet, and
received GEN at 20mg/kg body weight by gavage daily. The BGL and immune responses
(represented by serum antibodies, cytokines and chemokines, and histopathology)
were monitored, while the fecal gut microbiome was sequenced for 16S ribosomal
RNA to reveal any alterations in gut microbial communities. A significantly
reduced BGL was found in NOD males fed with soy-based diet on day 98 after
initial dosing, and an improved glucose tolerance was observed on both diets. In
addition, an anti-inflammatory response (suggested by reduced IgG2b and
cytokine/chemokine levels, and alterations in the microbial taxonomy) was
accompanied by an altered beta-diversity in gut microbial species. Among the NOD
females exposed to GEN, a later onset of T1D was observed. However, the profiles
of gut microbiome, antibodies and cytokines/chemokines were all indicative of pro
inflammation. This study demonstrated an association among GEN exposure, gut
microbiome alteration, and immune homeostasis in NOD males. Although the
mechanisms underlying the protective effects of GEN in NOD mice need to be
explored further, the current study suggested a GEN-induced sex-specific effect
in inflammatory status and gut microbiome.
PMID- 28412309
TI - The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs)
with important implication in immunity.
AB - We recently demonstrated the existence of a complex hormonal balance between
steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1)
expression and immune activation, suggesting that this scaffold protein may also
be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we
investigated the effect of the doping agent nandrolone, an androgen receptor (AR)
agonist, and of p,p'DDT (dichlorodiphenyltrichloroethane) and its main metabolite
p,p'DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist,
respectively, on RACK1 expression and innate immune response. In analogy to
endogenous androgens, nandrolone induced a dose-related increase in RACK1
transcriptional activity and protein expression, resulting in increased LPS
induced IL-8 and TNF-alpha production and proliferation in THP-1 cells.
Conversely, p,p'DDT and p,p'DDE significantly decrease RACK1 expression, LPS
induced cytokine production and CD86 expression; with p,p'DDE exerting a stronger
repressor effect than p,p'DDT, consistent with its stronger AR antagonistic
effect. These results indicate that RACK1 could be a relevant target of EDCs,
responding in opposite ways to agonist or antagonist of AR, representing a bridge
between the endocrine system and the innate immune system.
PMID- 28412310
TI - Increased seizure susceptibility and other toxicity symptoms following acute
sulforaphane treatment in mice.
AB - Activation of Nrf2 with sulforaphane has recently gained attention as a new
therapeutic approach in the treatment of many diseases, including epilepsy. As a
plant-derived compound, sulforaphane is considered to be safe and well-tolerated.
It is widely consumed, also by patients suffering from seizure and taking
antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many
natural remedies and dietary supplements may increase seizure risk and
potentially interact with antiepileptic drugs, the aim of our study was to
investigate the acute effects of sulforaphane on seizure thresholds and activity
of some first- and second-generation antiepileptic drugs in mice. In addition,
some preliminary toxicity profile of sulforaphane in mice after intraperitoneal
injection was evaluated. The LD50 value of sulforaphane in mice was estimated at
212.67mg/kg, while the TD50 value - at 191.58mg/kg. In seizure tests,
sulforaphane at the highest dose tested (200mg/kg) significantly decreased the
thresholds for the onset of the first myoclonic twitch and generalized clonic
seizure in the iv PTZ test as well as the threshold for the 6Hz-induced
psychomotor seizure. At doses of 10-200mg/kg, sulforaphane did not affect the
threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal
electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100mg/kg)
potentiated the anticonvulsant efficacy of carbamazepine in the maximal
electroshock seizure test. This interaction could have been pharmacokinetic in
nature, as sulforaphane increased concentrations of carbamazepine in both serum
and brain tissue. The toxicity study showed that high doses of sulforaphane
produced marked sedation (at 150-300mg/kg), hypothermia (at 150-300mg/kg),
impairment of motor coordination (at 200-300mg/kg), decrease in skeletal muscle
strength (at 250-300mg/kg), and deaths (at 200-300mg/kg). Moreover, blood
analysis showed leucopenia in mice injected with sulforaphane at 200mg/kg. In
conclusion, since sulforaphane was proconvulsant at a toxic dose, the safety
profile and the risk-to-benefit ratio of sulforaphane usage in epileptic patients
should be further evaluated.
PMID- 28412311
TI - Cross-national investigation of the drivers of obesity: Re-assessment of past
findings and avenues for the future.
AB - In this paper we question whether prior cross-national differences in food
attitudes still exist and if so, to what extent. Due to societal evolutions such
as sedentarism and globalization, international variations in food attitudes may
not be as pronounced as currently believed. A cross-sectional web-based survey
was carried out in the United States, the United Kingdom, France and Belgium. A
total of 2167 respondents (52% women; mean age = 39.0 years, SD = 11.4)
participated. To successfully combat obesity, a joint approach focusing on food
choice and physical activity is required; therefore we included behavioral
measures by means of choice tasks for these two important drivers. Further, the
extent to which respondents subscribe to the unhealthy = tasty intuition,
together with health and taste interest were investigated. Socio-demographic
information and self-reported heights and weights were also incorporated.
Logistic regressions were fitted with weight status as the dependent variable and
the attitudinal and behavioral measures as independent variables. Our findings
indicate that having a higher interest in healthy eating decreases the chance of
being overweight (odds = 0.88) and believing that unhealthy food is tasty
significantly increases the chance of being obese by 1.18 times. Overall, we find
that food attitudes have largely converged across the countries we investigated.
PMID- 28412312
TI - Updates to a 13C metabolic flux analysis model for evaluating energy metabolism
in cultured cerebellar granule neurons from neonatal rats.
AB - A hexose phosphate recycling model previously developed to infer fluxes through
the major glucose consuming pathways in cultured cerebellar granule neurons
(CGNs) from neonatal rats metabolizing [1,2-13C2]glucose was revised by
considering reverse flux through the non-oxidative pentose phosphate pathway
(PPP) and symmetrical succinate oxidation within the tricarboxylic acid (TCA)
cycle. The model adjusts three flux ratios to effect 13C distribution in the
hexose, pentose, and triose phosphate pools, and in TCA cycle malate to minimize
the error between predicted and measured 13C labeling in exported lactate (i.e.,
unlabeled, single-, double-, and triple-labeled; M, M1, M2, and M3,
respectively). Inclusion of reverse non-oxidative PPP flux substantially
increased the number of calculations but ultimately had relatively minor effects
on the labeling of glycolytic metabolites. From the error-minimized solution in
which the predicted M-M3 lactate differed by 0.49% from that measured by liquid
chromatography-triple quadrupole mass spectrometry, the neurons exhibited
negligible forward non-oxidative PPP flux. Thus, no glucose was used by the
pentose cycle despite explicit consideration of hexose phosphate recycling.
Mitochondria consumed only 16% of glucose while 45% was exported as lactate by
aerobic glycolysis. The remaining 39% of glucose was shunted to pentose
phosphates presumably for de novo nucleotide synthesis, but the proportion
metabolized through the oxidative PPP vs. the reverse non-oxidative PPP could not
be determined. The lactate exported as M1 (2.5%) and M3 (1.2%) was attributed to
malic enzyme, which was responsible for 7.8% of pyruvate production (vs. 92.2% by
glycolysis). The updated model is more broadly applicable to different cell types
by considering bi-directional flux through the non-oxidative PPP. Its application
to cultured neurons utilizing glucose as the sole exogenous substrate has
demonstrated substantial oxygen-independent glucose utilization by aerobic
glycolysis as well as the oxidative PPP and/or reverse non-oxidative PPP, but
negligible glucose consumption by the pentose cycle.
PMID- 28412313
TI - Is trial of labor harmful in breech delivery? A cohort comparison for breech and
vertex presentations.
AB - INTRODUCTION: Planned vaginal delivery in breech presentation is accompanied by
an excess neonatal risk that has, however, rarely been compared to that of
delivery in vertex presentation. Because of the severity of complications that
can occur in long-term follow-up, the risk of asphyxia is of particular concern.
MATERIAL AND METHODS: To assess immediate neonatal status after a planned vaginal
delivery of fetuses in breech compared with vertex presentation, we planned a
retrospective hospital cohort study of singleton term deliveries from 2000 to
2011. The indicators used to assess neonatal status were: 5-min Apgar score<7,
acidosis, both moderate (pH<7.15) and severe (pH<7.0), asphyxia (pH<7.0 and base
deficit>=12.0mmol/L), transfer to the neonatal intensive care unit (NICU), and in
hospital neonatal death. RESULTS: Compared with 43,595 trials of vaginal delivery
in vertex presentation at term during the 12-year study period (93.8% of all
vertex presentations), the 665 breech deliveries for which planned vaginal
delivery was planned (43.2% of all breech presentations) had a quadrupled risk of
severe acidosis (ORa 4.3 [2.2-7.5]), but no increase in the risk of asphyxia (ORa
0.7 [0.1-3.0]), NICU transfer (ORa 0.8 [0.4-1.3]) or in-hospital death (ORa 1.3
[0.1-6.0]). Moreover, compared with the 876 planned cesareans, the risk of severe
acidosis in the 665 trials of vaginal delivery in breech presentation was four
times higher (OR 4.3 [2.3-4.7]), but we observed no increase in neither asphyxia
nor other risks studied. CONCLUSION: In our hospital, planned vaginal delivery is
safe for breech presentations because it is associated with an increase of severe
acidosis but not asphyxia.
PMID- 28412314
TI - Improving students' ability to perform a standardized foetal biometry plane using
ultrasound simulators.
AB - OBJECTIVE: The objective of this study is to assess progress made in the
ultrasound (US) measurement of femur length (FL) by students after one hour of
training on US obstetric simulators. MATERIALS AND METHODS: Medical residents and
midwives registered for the 2016 French national foetal US diploma were invited
to a 1-hour US training course with simulators. The time to acquire the FL plane
with changing foetal presentation was prospectively measured before and after the
training. Every image was recorded, and quality criteria were assessed. RESULTS:
Thirty new learners trained in foetal US were evaluated. The time needed to
measure the FL was significantly shorter in the post-test versus the pre-test
(86s versus 125, P=0.015). The quality criteria were statistically similar before
and after training regarding the angle to horizontal (10.0 degrees versus 9.6
degrees , P=0.84) and FL (31.3mm versus 32.0mm, P=0.15). CONCLUSION: The time
needed to obtain the FL plane was reduced by 30% after a 1-hour US simulation
training session.
PMID- 28412315
TI - Reporting Compliance of Stroke Trials: Cross-Sectional Analysis.
AB - BACKGROUND: The FDA mandates timely reporting of all clinical trials conducted in
the United States. However, often the results are not reported in a timely
manner, resulting in wastage of finite resources. We assessed the reporting of
results of completed stroke trials and compared the reporting trends between U.S.
and non-U.S. stroke trials. METHODS: We assessed consecutive clinical stroke
trials registered as completed in ClinicalTrials.gov between January 1, 2008 and
January 1, 2015. Descriptive data collected included study phase, study type,
participant age, number of enrolled patients, study locations, start and primary
completion dates, result availability, time to reporting (months), sponsorship,
funding sources, and publication status. We also performed manual search for
stroke trials in Pubmed, Web of Science, and Google scholar. RESULTS: Out of a
total 140 completed trials, 39 trials (35,359 patients) involved at least 1 U.S.
center and 101 trials (58,542 patients) were conducted in non-U.S. centers. Of
the trials involving at least a single U.S. center, 31 of 39 (79%) reported their
results, whereas only 6 of 31 (19%) reported their results within 1 year. Of the
trials conducted at non-U.S. centers, 72 of 101 (71%) reported their results,
whereas results for 24 of 72 (33%) trials were available within a year of
completion. The time to reporting of results was significantly lower for all the
included clinical trials in the 2012-2014 period (P < .001, Cohen's d = .726) as
compared to the 2008-2011 period. CONCLUSION: Only one-fifth of completed stroke
trials involving at least a single U.S. center report their results within 1
year. Additionally, every fifth completed trial involving stroke patients at U.S.
centers remain unreported.
PMID- 28412316
TI - Differentiating Stroke and Seizure in Acute Setting-Perfusion Computed
Tomography?
AB - BACKGROUND: Perfusion computed tomography (PCT) is part of acute stroke protocol
in many hospitals; however, its clinical utility is still being disputed. Beyond
its use in core and penumbra estimation, there is also a question about PCT role
in stroke mimics diagnosis. Case series or small, retrospective studies showed
equivocal results. This is the first published prospective, comparative study on
PCT in differentiating stroke and seizure in acute setting. METHODS: Patients
with acute focal neurologic deficits and without acute ischemic lesions on
routine CT underwent PCT and electroencephalography (EEG) within 12 hours after
symptom onset. Perfusion parameters were set up as asymmetry indices for
corresponding regions of brain hemispheres. EEG findings were assigned to 1 of 5
classes. Neurologic examination was performed using the National Institutes of
Health Stroke Scale (NIHSS). Follow-up noncontrast computed tomography was
performed on the third day after symptom onset. If no CT changes appeared,
magnetic resonance diffusion-weighted imaging was conducted. RESULTS: Final
diagnosis was hemispheric ischemic stroke in 17 patients and focal neurologic
deficits in the course of seizures (post- and intraictally) in 12 patients. Those
groups were significantly different only in one single PCT parameter-time to peak
(TTP)-in the lateral part of the middle cerebral artery territory. Analyzed
groups were not significantly different in the NIHSS scores and the EEG
evaluation. CONCLUSIONS: TTP may stay relatively when seizure is a cause of focal
neurologic deficits, but not stroke. Further, large, prospective studies are
necessary to verify the results.
PMID- 28412317
TI - Medical Treatment for Spontaneous Anticoagulation-Related Intracerebral
Hemorrhage in the Netherlands.
AB - BACKGROUND: Spontaneous anticoagulation-related intracerebral hemorrhage accounts
for up to a quarter of spontaneous intracerebral hemorrhage cases and is
associated with higher hematoma volume and a worse outcome. Guidelines recommend
rapid anticoagulant reversal but mode and timing are not specified and optimal
strategy is uncertain. Variability in everyday practice is unknown. METHODS: An
invitation to a web-based survey was sent to 85 Dutch stroke neurologists in
different hospitals, with questions about importance, timing, and medical
management of spontaneous anticoagulation-related intracerebral hemorrhage.
RESULTS: In total, 61 (72%) neurologists completed the survey. Nearly all (97%)
deemed rapid anticoagulant reversal important. A local guideline for management
of anticoagulant reversal was used in 80% of the hospitals. Most neurologists
(56%) estimated anticoagulant reversal in anticoagulation-related intracerebral
hemorrhage to start later than intravenous thrombolysis in ischemic stroke. Few
(5%) thought it was quicker. A minority (28%) of the hospitals started
anticoagulation reversal without waiting for laboratory test results or
consulting a specialist in hemostasis. Prothrombin complex concentrate was used
by all neurologists for vitamin K antagonist reversal and by most (74%) for
reversal of thrombin inhibitors and factor Xa inhibitors (72%). Anticoagulation
reversal was initiated at the emergency department according to 89% of the
respondents. CONCLUSION: Variability in logistics in acute management of
spontaneous anticoagulation-related intracerebral hemorrhage was demonstrated.
Anticoagulant reversal is deemed important, but is estimated to have a longer
door-to-needle time than alteplase in thrombolysis for ischemic stroke by most
neurologists. Several delaying factors were found. These factors might have an
impact on outcome.
PMID- 28412318
TI - Nontraditional Lipid Variables Predict Recurrent Brain Ischemia in Embolic Stroke
of Undetermined Source.
AB - OBJECTIVE: The aims of this study are, first, to calculate the risk of brain
ischemia recurrence and embolic source diagnosis in the follow-up of patients
with ESUS (embolic stroke of undetermined source) and, second, to identify the
predictors of these events including cardiologic, laboratory, and clinical
factors. METHODS: A retrospective observational cohort study of stroke patients
admitted to the stroke unit in a single tertiary hospital from 2012 to 2014 was
performed. Patients fulfilling ESUS criteria were identified and followed by
medical history review until March 2016. Statistical analysis comprised Kaplan
Meier analysis and Cox proportional hazards multivariate analysis including
clinical characteristics, cardiologic data, and blood test results. RESULTS: One
hundred and thirteen patients, 8.3% of the overall stroke patients, filled ESUS
criteria and they were younger, had less vascular risk factors, and suffered
milder strokes than the remainder of stroke patients. Median follow-up of ESUS
was 25.6 months. Risk of brain ischemia recurrence was 8.4, 10.8, and 15% at 12,
24, and 36 months, respectively, and was associated to age (HR 1.07, P = .027)
and to a higher total cholesterol (TC)/high-density lipoprotein (HDL)-cholesterol
(HR = 1.38, P = .002) and low-density lipoprotein (LDL)-cholesterol/HDL
cholesterol ratios (HR = 1.48, P = .001). The risk of major embolic source
diagnosis was 6.7, 7.8, 13.6% at 12, 24, and 36 months, and was associated to
female sex (HR = 6.05, P = .021). CONCLUSIONS: Brain ischemia recurrence
increases with age and increased values of nontraditional lipid variables, TCHDLr
and LDLHDLr, in ESUS patients, and women are more frequently diagnosed with a
major embolic source in the follow-up.
PMID- 28412319
TI - Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control
and Vascular Events in Atrial Fibrillation.
AB - BACKGROUND: Warfarin has a narrow therapeutic window. We hypothesized that
genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1)
would show stronger associations than modifiable factors with the quality of
anticoagulation control and risks for thromboembolism and hemorrhage. METHODS: In
this retrospective cohort analysis, clinical and genetic data were collected from
380 patients with atrial fibrillation (AF) who were followed for an average
observation period of 4 years. We evaluated the factors associated with time in
therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular
events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and
VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin
dose assessment interval). RESULTS: The genotypic frequency of CYP2C9*3
(rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed
dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1
1173C>T than of the VKORC1 TT genotype (61.7 +/- 16.0% versus 56.7 +/- 17.4%, P =
.031). Multivariate testing showed that the VKORC1 genotype and anticoagulation
service were independently related to labile INRs (TTR <65%). Vascular events
were observed in 66 patients (18.4%) during the study period. A Cox proportional
hazard model showed that the use of anticoagulation service and patients'
characteristics, such as AF-thromboembolic risk (CHA2DS2-VASc score: Congestive
heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous
Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years,
female) and consequence (neurologic disability), but not genetic factors, were
independently associated with vascular events. CONCLUSIONS: Both genetic factor
(VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the
quality of anticoagulation control. However, clinical events were more strongly
associated with patient characteristics and clinical efforts than with genetic
factors.
PMID- 28412320
TI - Glibenclamide ameliorates cerebral edema and improves outcomes in a rat model of
status epilepticus.
AB - Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a
promising neuron protectant in various neurological disorders. This study aimed
to determine whether GBC improves survival and neurological outcome of status
epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h
(n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group
received a loading dose of 10 MUg/kg of GBC, followed by 1.2 MUg/6 h for 3 days,
while same dose of vehicle was used as control. The 28-day survival rate in the
GBC group (11/23) was significantly higher than that in the vehicle group (8/36).
In addition, the frequency and duration of spontaneous recurrent seizures in SE
rats were profoundly reduced by GBC but not by vehicle treatment. Moreover,
cognitive impairment was observed in the SE rats at day 28, which was reversed by
GBC treatment. Meanwhile, cerebral edema, as well as neuronal loss, was decreased
in several brain areas in the GBC group. Additionally, on the molecular basis,
the subunits of sulfonylurea receptor 1/transient receptor potential M4 (SUR1
TRPM4) heterodimer were both strongly upregulated after SE but partly suppressed
by GBC treatment. Furthermore, gene knockdown of Trpm4 in SE rats reduced BBB
disruption and neuronal loss, similar to the inhibitory effects with GBC
treatment. Taken together, GBC treatment markedly improved survival and
neurologic outcomes after SE. The salutary effects of GBC were correlated to the
alleviation of cerebral edema and reduction in neurological injury via down
regulation of SUR1-TRPM4 channel.
PMID- 28412321
TI - EGCG ameliorates diet-induced metabolic syndrome associating with the circadian
clock.
AB - In response to the daily light-dark (LD) cycle, organisms on Earth have evolved
with the approximately 24-h endogenous oscillations to coordinate behavioral and
physiological processes, including feeding, sleep, and metabolism homeostasis.
Circadian desynchrony triggered by an energy-dense diet rich in fats and fructose
is intimately connected with a series of metabolic disorders. Previous studies
revealed that (-)-Epigallocatechin-3-gallate (EGCG) could mitigate metabolic
misalignment; however, only a few reports have focused on its potential effect on
directly manipulating circadian rhythms to ameliorate metabolic syndrome. Our
goal was to investigate the regulating effect of EGCG treatment on metabolic
misalignment triggered by a high-fat and high-fructose diet (HFFD) associating
with the circadian clock. Our results indicated that HFFD treatment partially
exhibited poor circadian oscillations of the core clock gene and the clock
controlled gene in the liver and fat relative to the control group. EGCG
administration may ameliorate the diet-dependent decline in circadian function by
controlling the Sirt1-PGC1alphaloop, implying the existence of an EGCG
entrainable oscillator. Subsequently, reducing fatty acid synthesis and elevating
beta-oxidation in the liver coupled with the increasing brown adipose tissue
(BAT) energy expenditure observed in the EGCG group of mice prevented the
adipocyte hypertrophy and fat accumulations common to BAT and white adipose
tissue (WAT) derived from the HFFD mice. This study is the first to provide
compelling evidences that EGCG may ameliorate diet-induced metabolic misalignment
by regulating the rhythmic expression of the circadian clock genes in the liver
and fat.
PMID- 28412322
TI - MicroRNA-130b transcriptionally regulated by histone H3 deacetylation renders Akt
ubiquitination and apoptosis resistance to 6-OHDA.
AB - Apoptosis of DA neurons is a contributing cause of disability and death for
Parkinson's disease (PD). Akt may become a potential therapeutic target for PD
since Akt has been deactivated during DA neuron apoptosis. We previously
demonstrated that Akt confers apoptosis resistance against 6-OHDA in DA neuron
like PC12 cells, yet the underlying mechanisms accounted for this are not fully
understood. Here we report that microRNA-130b (miR-130b)-dependent and
cylindromatosis (CYLD) repression-mediated Akt ubiquitination renders apoptosis
resistance of PC12 cells to 6-OHDA, which elicits histone H3 deacetylation
induced transcriptional downregulation of miR-130b vice versa. CYLD deficiency
ubiquitinates Akt at Lys63, thereby phosphorylating Akt and antagonizing 6-OHDA
initiated apoptosis. MiR-130b targetedly represses CYLD and increases apoptosis
resistance to 6-OHDA. CYLD repression by miR-130b restores Akt ubiquitination and
activation, GSK3beta and FoxO3a phosphorylation, FoxO3a removal from Bim promoter
as well as Bim downregulation during 6-OHDA administration. CYLD deficiency
mediated Akt activation is instrumental for the apoptosis-resistant phenotypes of
miR-130b. In addition, 6-OHDA transcriptionally downregulates miR-130b through
recruitment of HDAC3 at the promoter. Furthermore, EPO potentiates the ability of
miR-130b to activate Akt and augment apoptosis resistance. Our findings identify
the apoptosis-resistant function of miR-130b and suggest that histone H3
deacetylation plays a pivotal role in regulating miR-130b transcription in
response to 6-OHDA.
PMID- 28412324
TI - Nanoformulation-based sequential combination cancer therapy.
AB - Although combining two or more treatments is regarded as an indispensable
approach for effectively treating cancer, the traditional cocktail-based
combination therapies are seriously limited by coordination issues that fail to
account for differences in the pharmacokinetics and action sites of each drug.
The careful manipulation of dosing regimens, such as by the sequential
application of combination treatments, may satisfy the temporal and spatial needs
of each drug and achieve successful combination antitumor therapy. Nanotechnology
based carriers might be the best tools for sequential combination therapy, as
they can be loaded with multiple cargos and may provide targeted and sustained
delivery to target tumor cells. Single nanoformulations capable of sequentially
releasing drugs have shown synergistic anticancer activity, such as by
sensitizing tumor cells through cascaded drug delivery or remodeling the tumor
vasculature and microenvironment to enhance the tumor distribution of
nanotherapeutics. This review highlights the use of nanotechnology-based
multistage drug delivery for cancer treatment, focusing on the ability of such
formulations to enhance antitumor efficacy by applying sequential treatment and
modulating dosing regimens, which are challenges currently being faced in the
clinic.
PMID- 28412323
TI - Single CpG site methylation controls estrogen receptor gene transcription and
correlates with hormone therapy resistance.
AB - Hormone therapy is the most effective treatment for patients with estrogen
receptor alpha-positive breast cancers. However, although resistance occurs
during treatment in some cases and often reflects changed estrogen receptor alpha
status, the relationship between changes in estrogen receptor alpha expression
and resistance to therapy are poorly understood. In this study, we identified a
mechanism for altered estrogen receptor alpha expression during disease
progression and acquired hormone therapy resistance in aromatase inhibitor
resistant breast cancer cell lines. Subsequently, we investigated promoter
switching and DNA methylation status of the estrogen receptor alpha promoter, and
found marked changes of methylation at a single CpG site (CpG4) in resistant
cells. In addition, luciferase reporter assays showed reduced transcriptional
activity from this methylated CpG site. This CpG region was also completely
conserved among species, suggesting that it acts as a methylation-sensitive Ets-2
transcription factor binding site, as confirmed using chromatin
immunoprecipitation assays. In estrogen receptor alpha-positive tumors, CpG4
methylation levels were inversely correlated with estrogen receptor alpha
expression status, suggesting that single CpG site plays an important role in the
regulation of estrogen receptor alpha transcription.
PMID- 28412325
TI - Designing metal-contained enzyme mimics for prodrug activation.
AB - Enzyme-activated prodrug therapy (EAPT) is a widely-used and effective treatment
method for cancer by converting prodrugs into drugs at the demanded time and
space, whose key step is prodrug activation. Traditional prodrug activations are
mostly dependent on natural enzymes, which are unstable, expensive and hard to be
functionalized. The emerging enzyme mimics, especially the metal-contained enzyme
mimics (MEMs), provide a potential chance for improving the traditional EAPT
because of their high stability, low cost and easiness of preparation and
functionalization. The existing MEMs can be classified into three categories:
catalytic core-scaffold MEM (csMEM), nanoparticle MEM (npMEMs) and metal-organic
framework (MOF) MEM (mofMEM). These MEMs can mimic diverse functions
corresponding to natural enzymes, and some of which are potentially used in
prodrug activation, such as DNase, RNase, carbonate esterase, etc. In this
review, we briefly summarize the MEMs according to their structure and
composition, and highlight the successful and potential applications for prodrug
activation mediated by hydrolase-like and oxidoreductase-like MEMs.
PMID- 28412326
TI - No Acute Changes in LVEF Observed With Concurrent Trastuzumab and Breast
Radiation With Low Heart Doses.
AB - INTRODUCTION/BACKGROUND: Treatment for HER2-postitive breast cancer often
includes trastuzumab, breast/chest wall (CW) radiation (RT), and anthracyclines,
all of which have cardiac toxicity. We aimed to evaluate the relationship between
heart dose and acute left ventricular ejection fraction (LVEF) changes in
patients who received concurrent trastuzumab and breast/CW RT with and without
anthracycline use. PATIENTS AND METHODS: We retrospectively reviewed all
nonmetastatic breast cancer patients from 2008 to 2015 who received concurrent
trastuzumab and breast/CW RT. Baseline LVEF was compared with the LVEF closest to
treatment completion as well as with the lowest post-treatment LVEF. LVEF changes
were correlated with laterality, heart dosimetric parameters, and doxorubicin
use. RESULTS: Eighty-eight patients were included in our analysis. The median
follow-up was 45 months. Forty-one patients were right-sided and 47 left-sided.
Thirty-one patients received doxorubicin, 16 right-sided and 15 left-sided. Mean
heart dose was 1.10 Gy and 3.63 Gy for right- and left-sided patients,
respectively (P < .001). In the entire cohort, a significant LVEF decrease of
3.0% was observed pre- and post-treatment. There was a significant effect of
doxorubicin (P = .013) and a nonsignificant effect of RT laterality (P = .088) on
LVEF change. The test of interaction between doxorubicin and laterality was not
significant (P = .90). No significant association was found between LVEF change
and heart dosimetric parameters, including percent volume of heart receiving 5 Gy
(V5), 10 Gy (V10), 20 Gy (V20), and 45 Gy (V45), and maximum dose. Similar
results were found when baseline LVEF was compared with the lowest post-treatment
LVEF. CONCLUSION: With cardiac doses < 4 Gy, declines in LVEF were not related to
tumor laterality or heart dosimetric parameters. Statistically significant LVEF
decreases were mainly attributed to doxorubicin.
PMID- 28412327
TI - Place over traits? Purchasing edibles from medical marijuana dispensaries in Los
Angeles, CA.
AB - OBJECTIVES: To examine discrete purchasing behaviors of marijuana-infused edibles
from medical marijuana dispensaries with the aim to identify potential venue- and
individual-level targets for prevention. METHODS: Two-stage, venue-based sampling
approach was used to randomly select patrons exiting 16 medical marijuana
dispensaries in Los Angeles, California during Spring 2013. Hierarchical
generalized linear modeling was used to examine the likelihood of purchasing
edibles among 524 patrons reporting a discrete purchase regressed on
characteristics of the sampled dispensaries and their patrons. RESULTS: At a
venue level, patrons were more likely to purchase edibles from dispensaries
located within Census tracts with higher median incomes or in close proximity to
a higher number of dispensaries. At an individual level, patrons who identified
as Black or Hispanic were associated with a lower likelihood of purchasing
edibles when compared to patrons who identified as other non-White, non-Hispanic
race/ethnicity. CONCLUSIONS: Place-based policies focused on regulating edible
sales through dispensaries may be fruitful in influencing access to edibles.
Additionally, social marketing campaigns may benefit from targeting both
locations where edible purchases are more likely and populations who are more
likely to purchase edibles.
PMID- 28412328
TI - Budded baculovirus particles as a source of membrane proteins for radioligand
binding assay: The case of dopamine D1 receptor.
AB - INTRODUCTION: G-protein-coupled receptors have become very important drug targets
and therefore ligand binding assays for these receptors are an essential part of
drug discovery. Among a variety of experimental systems, the radioligand binding
assay has remained as one of the main methods in this field for decades. Usually
cell membranes or tissues are used in these experiments, however in this article
we demonstrate that baculoviruses produced in Sf9 cells display recombinant
receptors on their surface and therefore can be used in radioligand binding
assay. METHODS: We have used baculoviruses with dopamine D1 receptors as a model
system to validate the usage of this receptor preparation in radioligand binding
experiments. In order to collect membrane receptors and separate free
radioligand, we have applied FilterMate Harvester with Filtermat B. RESULTS:
Using baculoviruses with dopamine D1 receptors as a model system, we have shown
that this is a suitable preparation for conventional radioligand binding assay.
Here, all the experiments were performed using the dopamine D1-like receptor
specific radioligand [3H]SCH23390. There were no significant differences between
binding parameters determined in membranes of Sf9 cells and baculovirus
particles. Similar pIC50 and Ki values were also determined in competition
binding assays with HEK293 cell membranes. DISCUSSION: All the results obtained
with baculovirus preparation were in good agreement with the data obtained in
parallel experiments with membrane preparations from Sf9 and HEK293 cells
expressing dopamine D1 receptors. Shape uniformity, homogeneous distribution and
slow sedimentation of the membranes are some of the advantages of baculovirus
preparations, which prove them as promising source of membrane proteins for
routine and high throughput analysis.
PMID- 28412329
TI - Comparison of pro-amnesic efficacy of scopolamine, biperiden, and phencyclidine
by using passive avoidance task in CD-1 mice.
AB - INTRODUCTION: Memory disorders accompany numerous diseases and therapies, and
this is becoming a growing medical issue worldwide. Currently, various animal
models of memory impairments are available; however, many of them require high
financial outlay and/or are time-consuming. A simple way to achieve an efficient
behavioral model of cognitive disorders is to inject defined drug that has pro
amnesic properties. Since the involvement of cholinergic and glutamatergic
neurotransmission in cognition is well established, the utilization of a
nonselective muscarinic receptor antagonist, scopolamine (SCOP), a selective M1
muscarinic receptor antagonist, biperiden (BIP), and a non-competitive N-methyl-d
aspartate (NMDA) receptor antagonist, phencyclidine (PCP) seems to be reliable
tools to induce amnesia. As the determination of their effective doses remains
vague and the active doses vary significantly in laboratory settings and in mouse
species being tested, the aim of this study was to compare these three models of
amnesia in CD-1 mice. METHODS: Male Swiss Albino mice were used in passive
avoidance (PA) test. All the compounds were administered intraperitoneally (ip)
at doses 1mg/kg, 5mg/kg, and 10mg/kg (SCOP and BIP), and 1mg/kg, 3mg/kg, and
6mg/kg (PCP). RESULTS: In the retention trial of the PA task, SCOP and PCP led to
the reduction of step-through latency at all the tested doses as compared to
control, but BIP was effective only at the dose of 10mg/kg. CONCLUSION: This
study revealed the effectiveness of SCOP, PCP, and BIP as tools to induce
amnesia, with the PCP model being the most efficacious and SCOP being the only
model that demonstrates a clear dose-response relationship.
PMID- 28412330
TI - Re: Cambareri et al.: Do Overweight and Obese Pediatric Stone Formers Have
Differences in Metabolic Abnormalities Compared With Normal-weight Stone Formers?
(Urology 2017;101:26-30).
PMID- 28412331
TI - Are We Using the Best Tumor Size Cut-points for Renal Cell Carcinoma Staging?
AB - OBJECTIVE: To compare the predictive ability for oncologic outcomes among current
tumor size cut-points and clinically relevant alternatives to determine which are
optimal. METHODS: Patients who underwent radical or partial nephrectomy between
1970 and 2010 for T1-2Nx/N0M0 renal cell carcinoma (RCC) were identified.
Associations between tumor size and progression-free survival (PFS) and cancer
specific survival (CSS) were evaluated using Kaplan-Meier analyses and Cox
models. Predictive ability was assessed using c-indexes. RESULTS: The cohort
included 3304 patients with a median age of 63 years (interquartile range 53,
70). Median follow-up among survivors was 9.9 years (interquartile range 6.9,
14.3). There were 536 patients who progressed and 354 who died from RCC. For RCC
tumors <=3.0 cm, 10-year PFS and CSS rates were 93%-95% and 97%-99%,
respectively. For tumors >3.0-4.0 cm, PFS and CSS began to decline (91% and 95%,
respectively), with further gradual declines in PFS and CSS with increasing tumor
size. Plots of hazard ratios for progression and RCC death as a function of tumor
size did not reveal major inflection points. Differences in discrimination based
on various combinations of tumor-size cut-points for progression or RCC death
were small, with c-indexes ranging between 0.691-0.704 and 0.734-0.750,
respectively. CONCLUSION: RCC tumors <=3.0 cm in size are associated with
favorable outcomes. Thereafter, risks of progression and RCC death increase
gradually with tumor size, with no compelling biological reason to endorse a
given cut-point over another.
PMID- 28412332
TI - Congenital Aphallia: Novel Use of Acellular Dermal Matrix During Scrotal Flap
Phalloplasty.
AB - Phallic reconstruction is an important part of management for congenital
aphallia. Scrotal flap phalloplasty has been described in pediatric patients to
create the appearance of a nonfunctioning phallus. We describe a modified scrotal
flap technique with the addition of an acellular dermal matrix patch (AlloDerm)
to provide additional girth and support to the phallus. The postoperative
cosmetic outcome has been satisfactory and there is no documented complication
over a 12-month follow-up. AlloDerm dermal matrix can be a safe addition to
phallic reconstruction and its overall application needs to be further studied.
PMID- 28412333
TI - Reply by the Authors.
PMID- 28412334
TI - Ovotestis in Adolescence: 2 Case Reports.
AB - We present 2 patients found to have ovotesticular disorder of sexual development
(otDSD) in late adolescence. Two 15-year-old phenotypically male patients
presented to a large pediatric hospital with different complaints: 1 with concern
for testicular rupture after a straddle injury; 1 with gynecomastia. Further
workup, including imaging and laboratory tests, was performed before surgical
exploration. The first patient had unilateral ovotestis, contralateral testis,
and SRY-negative 46,XX karyotype. The second patient with gynecomastia had
unilateral ovotestis with hemi-uterus and fallopian tube, contralateral ovarian
tissue, and 46,XX/47,XXY Klinefelter mosaic karyotype. Although rare,
phenotypically normal male patients may present later with ovotesticular disorder
of sexual development.
PMID- 28412335
TI - Metabolic Syndrome Does Not Increase the Risk of Ejaculatory Dysfunction in
Patients With Lower Urinary Tract Symptoms and Benign Prostatic Enlargement: An
Italian Single-center Cohort Study.
AB - OBJECTIVE: To evaluate the relationship between metabolic syndrome (MetS) and
ejaculatory dysfunction (EjD) in patients with lower urinary tract symptoms and
benign prostatic enlargement. MATERIALS AND METHODS: From 2012 to 2016, a
consecutive series of men with lower urinary tract symptoms and benign prostatic
enlargement who were attending our prostate clinic were evaluated using the
International Prostate Symptom Score (IPSS) and were subsequently enrolled into a
prospective database. All patients were assessed using the short form of the
International Index of Erectile Function (IIEF-SF) and the Male Sexual Health
Questionnaire ejaculatory dysfunction short form (MSHQ-EjD-SF) that evaluates the
ability to ejaculate, the ejaculation force, the ejaculation volume, and
subjective bother associated with EjD. MetS was defined according to the Adult
Treatment Panel III criteria. RESULTS: A total of 220 patients were enrolled; 48
of 220 patients (22%) presented a MetS. Mean age was 70 +/- 8 years, mean IPSS
was 8.3 +/- 6.2, mean IIEF score was 17.3 +/- 7.9, and mean MSHQ-EjD-SF was 9.9
+/- 4.7. Overall, 109 of 220 patients (50%) were affected by a moderate or severe
EjD. On multivariate analysis, age (odds ratio [OR]: 1.058, 95% confidence
interval [CI]: 1.016-1.123; P = .007), IIEF score (OR: 0.899, 95% CI: 0.856
0.943; P = .000), and IPSS (OR: 1.065, 95% CI: 1.011-1.123; P = .018) were found
to be predictors of EjD. In our series MetS was not found to be predictive of
EjD. CONCLUSION: In our single-center study, MetS has no influence on the EjD
evaluated with the MSHQ-EjD-SF.
PMID- 28412336
TI - Antiageing activities of water-soluble chitosan from Clanis bilineata larvae.
AB - Water extracts were prepared using water-soluble chitosan from Clanis bilineata
larva skin. This study also investigated antioxidant and antiageing activities of
water-soluble chitosan. Water-soluble chitosan of Clanis bilineata larva skin
(CBLSWSC) showed considerable scavenging activities on superoxide anion and
hydroxyl radicals and reducing capacity. Different doses of CBLSWSC were
intragastrically administered on a d-galactose-induced-aged mouse model over a
period of six weeks. Intragastric CBLSWSC administration significantly increased
activities of superoxide dismutase and glutathione peroxidase and inhibited
formation of malondialdehyde in brains and sera of mice in a dose-dependent
manner. Results suggest that CBLSWSC exhibits high antioxidant activity and can
be developed as potential dietary supplement to retard ageing in humans.
PMID- 28412337
TI - An overview on molecular chaperones enhancing solubility of expressed recombinant
proteins with correct folding.
AB - The majority of research topics declared that most of the recombinant proteins
have been expressed by Escherichia coli in basic investigations. But the majority
of high expressed proteins formed as inactive recombinant proteins that are
called inclusion body. To overcome this problem, several methods have been used
including suitable promoter, environmental factors, ladder tag to secretion of
proteins into the periplasm, gene protein optimization, chemical chaperones and
molecular chaperones sets. Co-expression of the interest protein with molecular
chaperones is one of the common methods The chaperones are a group of proteins,
which are involved in making correct folding of recombinant proteins. Chaperones
are divided two groups including; cytoplasmic and periplasmic chaperones.
Moreover, periplasmic chaperones and proteases can be manipulated to increase the
yields of secreted proteins. In this article, we attempted to review cytoplasmic
chaperones such as Hsp families and periplasmic chaperones including; generic
chaperones, specialized chaperones, PPIases, and proteins involved in disulfide
bond formation.
PMID- 28412338
TI - Purification, in vitro antioxidant and in vivo anti-aging activities of
exopolysaccharides by Agrocybe cylindracea.
AB - The in vitro antioxidant and in vivo anti-aging activities in D-galactose-induced
aging mice of exopolysaccharides (EPS) and its fractions (EPS-1, EPS-2 and EPS-3)
by Agrocybe cylindraceas were investigated presently. The scavenging effects of
EPS-2 on hydroxyl (HO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were
97.1+/-4.25% and 90.23+/-3.25%, while the reducing power reached 1.18+/-0.08 at
120mg/L, which were higher than EPS, EPS-1 and EPS-3 at 1000mg/L. The EPS showed
potential anti-aging activities via reducing the contents of malonaldehyde (MDA)
and total cholesterol (TC), as well as increasing the activities of superoxide
dismutase (SOD) activities, glutathione peroxidase (GSH-Px) activities, and total
antioxidant capacity (T-AOC). Additionally, the monosaccharide analysis showed
EPS contained rhamnose and glucose with the molar ratio of 2.8:1. These results
demonstrated that EPS could be used as functional foods and natural drugs on
preventing and mitigating the aging process.
PMID- 28412339
TI - Purification and functional properties of a novel glucoamylase activated by
manganese and lead produced by Aspergillus japonicus.
AB - Microbial amylases are used to produce ethanol, glucose and can be applied in
textiles products, detergents and other industries. This study aimed to determine
the best carbon source concentration to induce the amylase production by A.
japonicus, and its purification and biochemical characterization. For that, this
fungus was cultivated in Khanna medium, pH 5.5, for 4 days, at 25 degrees C, in
static condition, supplemented with potato starch and maltose in different
concentrations. The fungal crude enzymatic extract was purified in a unique
elution in DEAE-cellulose column and the molecular mass was determined as 72kDa.
The optimum temperature and pH was 65 degrees C and 5.0, respectively. Amylase
remained 75% of its activity after one hour at 50 degrees C and was stable in the
pH range 3.0-7.0. The analysis of the end-products by thin layer chromatography
showed only glucose formation, which characterizes the purified enzyme as a
glucoamylase. Amylopectin was the best substrate for the enzyme assay and Mn+2
and Pb+2 were good glucoamylase activators. This activation, in addition to the
biochemical characteristics are important results for future biotechnological
applications of this glucoamylase in the recycling and deinking process by the
paper industries.
PMID- 28412340
TI - Levan promotes antiproliferative and pro-apoptotic effects in MCF-7 breast cancer
cells mediated by oxidative stress.
AB - Exopolysaccharides are high-valued bio-products produced by various microbial
species and have been described to possess biological response modifying
activities. These bio-products have been effective as therapeutic agents in
various human disease conditions. The objective of this study was to examine the
effects of levan (a (2->6)-beta-d-fructan) produced on sucrose by the halophilic
bacterium, Halomonas smyrnensis AAD6T, in human breast cancer MCF-7 cells. MCF-7
cells were exposed to levan for 24 and 48h. The antiproliferative activity was
analyzed by the MTT assay. Oxidative stress was measured by the CM-H2DCFDA assay,
and cell apoptosis was analyzed by the caspase-3/7 assay. Cell cycle was analyzed
by flow cytometry and gene expression was determined by RT-PCR. Levan showed a
time- and concentration-dependent antiproliferative activity, and this effect was
associated with an increase in cell apoptosis and oxidative stress. In addition,
levan increased the gene expression of p53 and p27. Here we demonstrated that
levan exhibited an antiproliferative effect that was mediated by an increase in
apoptosis and oxidative stress.
PMID- 28412341
TI - Chitosan: A potential biopolymer for wound management.
AB - It has been seen that slow healing and non-healing wounds conditions are
treatable but still challenging to humans. Wound dressing usually seeks for
biocompatible and biodegradable recipe. Natural polysaccharides like chitosan
have been examined for its antimicrobial and healing properties on the basis of
its variation in molecular weight and degree of deacetylation. Chitosan adopts
some vital characteristics for treatment of various kinds of wounds which include
its bonding nature, antifungal, bactericidal and permeability to oxygen. Chitosan
therefore has been modified into various forms for the treatment of wounds and
burns. The purpose of this review article is to understand the exploitation of
chitosan and its derivatives as wound dressings. This article will also provide a
concise insight on the properties of chitosan necessary for skin healing and
regeneration, particularly highlighting the emerging role of chitosan films as
next generation skin substitutes for the treatment of full thickness wounds.
PMID- 28412342
TI - Recent advances in the development of novel protein scaffolds based therapeutics.
AB - Antibodies occupy a central position when it comes to binding proteins with
desired antigenic specificities. During the past decade, a plethora of
recombinant or humanized versions of antibodies have entered clinical settings
with outstanding accomplishments. Yet, they suffer from several drawbacks such as
high molecular weight, limited tissue penetration, instability, high production
cost, requirement for large doses and potential cytotoxicity. As a result, new
generation of receptor proteins has been developed, that are derived from small
and robust immunoglobulin (Ig) or non-immunoglobulin based "scaffolds".
Combinatorial protein engineering has tremendous scope in the development of
these protein scaffolds with immunoglobulin like specificity and/or prescribed
binding functions. The advancement made in this regard can boast of developing
various validated Ig based and non-Ig protein scaffolds with desirable
therapeutic potential. The newly emerging technology has profound scope in
translational biology and offer matching replacement for existing
immunotherapeutic agents. Only few data from early clinical studies are available
yet, but many more are likely to come in the near future. Here, we provide a
glimpse of recent clinical advances in the field of existing protein scaffolds.
PMID- 28412343
TI - Structural characterization and immunomodulatory activity of a novel
polysaccharide from Pteridium aquilinum.
AB - PAP1-A, a novel heteropolysaccharide with an average molecular mass of
1.35*105Da, was isolated from Pteridium aquilinum using a combination of
chromatography by DEAE Sepharose Fast Flow and Sepharose 4B. The monosaccharide
component of PAP1-A was L-rhamnose, L-arabinose, L-fucose, D-xylose, D-mannose, D
glucose and D-galactose in the molar ration of 1.82: 1.53: 1.42: 1.31: 5.24: 1:
12.35. The predicted structure of PAP1-A was established to be a complex
polysaccharide with a main chain consisted of alpha-(1->4)-linked galactose
partially substituted at O-6 position, with the (1->2)-linked xylose, (1->3)
linked arabinose, (1->3)-linked rhamnose, (1->3,6)-linked mannose, and (1->6)
linked mannose, as branches. Fucose, glucose, mannose, and rhamnose were located
at the termini of the branches. The immunomodulatory activity assay showed that
PAP1-A could significantly promote the RAW264.7 cells proliferation and induce
the production of NO from RAW264.7 cells. Therefore, PAP1-A shows as a potent
immunomodulator with potential applications in the medical and food industries.
PMID- 28412344
TI - Insights into structure and function of high pressure-modified starches with
different crystalline polymorphs.
AB - The effect of high pressure (HP) treatment at 200-600MPa for 30min on properties
of three starches with different polymorphs was investigated. HP treatment
altered greatly the morphology of wheat starch, especially at 400MPa or higher.
The crystallinity of wheat starch decreased from 22.6% for native starch to 3.4%
for starch after treatment at 600MPa. The short-range molecular order as measured
by FTIR and Raman spectroscopy decreased with increasing treatment pressure. HP
treatment had little effect on structural properties of potato and yam starches,
except for yam starch after treatment at 600MPa. HP treatment decreased the
pasting viscosities of wheat starch except for the treatment at 200MPa, which
increased the peak, trough and final viscosities by 6.7, 11.1 and 5.7%,
respectively. The peak viscosity of potato and yam starches was increased
respectively by 14.0 and 11.3% after HP treatment at 600MPa. HP treatment at
600MPa enhanced greatly the final digestion percentages of wheat and yam starch
by 20 and 26.4%, but had little effect on potato starch. The above results showed
that wheat starch was more susceptible to the effects of HP treatment than did
yam and potato starches, and that C-type yam starch behaved more likely the B
type potato starch to HP treatment.
PMID- 28412345
TI - A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via
suppressing miR-141 by targeting TGF-beta1.
AB - Circular RNAs (circRNAs) are a novel type of endogenous noncoding RNA gaining
research interest in recent years. Despite this increase in interest, the
mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases,
particularly myocardial fibrosis, is rarely reported. In the following study, the
expression profiles and potential mechanisms of circRNAs in mice myocardial
fibrosis models in vitro are investigated. Previous research examining circRNA
expression profiles of diabetic db/db mice myocardium using circRNA microarray
found 43 circRNAs were abnormally expressed, including 24 up-regulated circRNAs
and 19 down-regulated circRNAs. Furthermore, circRNA_010567 was markedly up
regulated in diabetic mice myocardium and cardiac fibroblasts (CFs) treated with
Ang II. Bioinformatics analysis predicted circRNA_010567, sponge miR-141 and miR
141 directly target TGF-beta1, which was validated by dual-luciferase assay.
Subsequently, functional experiments revealed circRNA_010567 silencing could up
regulate miR-141 and down-regulate TGF-beta1 expression, and suppress fibrosis
associated protein resection in CFs, including Col I, Col III and alpha-SMA.
Results demonstrate the circRNA_010567/miR-141/TGF-beta1 axis plays an important
regulatory role in the diabetic mice myocardial fibrosis model. The present study
characterizes a new function of circRNA in the pathogenesis of myocardial
fibrosis in a diabetic mouse model, providing novel insight for circRNA-miRNA
mRNA in cardiovascular disease.
PMID- 28412346
TI - Superoxide is the critical driver of DOPAL autoxidation, lysyl adduct formation,
and crosslinking of alpha-synuclein.
AB - Parkinson's disease has long been associated with redox imbalance and oxidative
stress in dopaminergic neurons. The catecholaldehyde hypothesis proposes that 3,4
dihydroxyphenylacetaldehyde (DOPAL), an obligate product of dopamine catabolism,
is a central nexus in a network of pathways leading to disease-state
neurodegeneration, owing to its toxicity and potent ability to oligomerize alpha
synuclein, the main component of protein aggregates in Lewy bodies. In this work
we examine the connection between reactive oxygen species and DOPAL autoxidation.
We show that superoxide propagates a chain reaction oxidation, and that this
reaction is dramatically inhibited by superoxide dismutase. Moreover, superoxide
dismutase prevents DOPAL from forming dicatechol pyrrole adducts with lysine and
from covalently crosslinking alpha-synuclein. Given that superoxide is a major
radical byproduct of impaired cellular respiration, our results provide a
possible mechanistic link between mitochondrial dysfunction and synuclein
aggregation in dopaminergic neurons.
PMID- 28412347
TI - Interaction of KRas4b with anionic membranes: A special role for PIP2.
AB - KRas4b is a small G-protein whose constitutively active oncogenic mutants are
present in 90% of pancreatic cancers. Using fully post-translationally modified
KRAS4b, we investigated the role of lipid identity in the recruitment of KRas4b
to a membrane surface of defined composition. Application of a newly developed
single frequency fluorescence anisotropy decay experiment to this system revealed
that KRas4b has a significant binding preference for Nanodisc bilayers containing
PIP2. We conducted molecular dynamics simulations to look for an origin of this
specificity. In the case of membranes containing PIP2 the protein formed long
lived salt bridges with PIP2 head groups but not the monovalent DMPS, explaining
the experimentally observed lipid specificity. Additionally, we report that PIP2
forms key contacts with Helix-4 on the catalytic domain of KRas4b that orient the
protein in a manner expected to facilitate association with upstream and
downstream signaling partners.
PMID- 28412348
TI - Closed-channel culture system for efficient and reproducible differentiation of
human pluripotent stem cells into islet cells.
AB - Human pluripotent stem cells (hPSCs) are thought to be a promising cell-source
solution for regenerative medicine due to their indefinite proliferative
potential and ability to differentiate to functional somatic cells. However,
issues remain with regard to achieving reproducible differentiation of cells with
the required functionality for realizing human transplantation therapies and with
regard to reducing the potential for bacterial or fungal contamination. To meet
these needs, we have developed a closed-channel culture device and corresponding
control system. Uniformly-sized spheroidal hPSCs aggregates were formed inside
wells within a closed-channel and maintained continuously throughout the culture
process. Functional islet-like endocrine cell aggregates were reproducibly
induced following a 30-day differentiation protocol. Our system shows an easily
scalable, novel method for inducing PSC differentiation with both purity and
functionality.
PMID- 28412349
TI - Light-induced protein degradation in human-derived cells.
AB - Controlling protein degradation can be a valuable tool for posttranslational
regulation of protein abundance to study complex biological systems. In the
present study, we designed a light-switchable degron consisting of a light oxygen
voltage (LOV) domain of Avena sativa phototropin 1 (AsLOV2) and a C-terminal
degron. Our results showed that the light-switchable degron could be used for
rapid and specific induction of protein degradation in HEK293 cells by light in a
proteasome-dependent manner. Further studies showed that the light-switchable
degron could also be utilized to mediate the degradation of secreted Gaussia
princeps luciferase (GLuc), demonstrating the adaptability of the light
switchable degron in different types of protein. We suggest that the light
switchable degron offers a robust tool to control protein levels and may serves
as a new and significant method for gene- and cell-based therapies.
PMID- 28412350
TI - Patient sample-oriented analysis of gene expression highlights extracellular
signatures in breast cancer progression.
AB - Although a large collection of cancer cell lines are useful surrogates for
patient samples, the physiological relevance of observed molecular phenotypes in
cell lines remains controversial. Because transcriptome data are a representative
set of molecular phenotypes in cancers, we systematically analyzed the
discrepancy of global gene expression profiles between patient samples and cell
lines in breast cancers. While the majority of genes exhibited general
consistency between patient samples and cell lines, the expression of genes in
the categories of extracellular matrix, collagen trimers, receptor activity,
catalytic activity and transporter activity were significantly up-regulated only
in tissue samples. Genes in the extracellular matrix, particularly collagen
trimers, showed a wide variation of expression in tissue, but minimal expression
and variation in cell lines. Further analysis of tissue samples exclusively
revealed that collagen genes exhibited a cancer stage-dependent expressional
variation based on their supramolecular structure. Prognostic collagen biomarkers
associated with survival rate were also readily predicted from tissue-oriented
transcriptome analysis. This study presents the limitations of cell lines and the
exclusive features of tissue samples in terms of functional categories of the
cancer transcriptome.
PMID- 28412351
TI - Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in
hepatocytes.
AB - ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear.
SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been
shown to be involved in anti-inflammation and associated with a number of human
diseases. In this study, we revealed that ApoA4 stimulates the gene expression of
SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time
dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated
through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the
SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and
RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that
ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our
findings may throw light on the function of ApoA4 in inflammatory responses and
acute-phase reactions, as well as the development of SERPINA3 relative diseases.
PMID- 28412352
TI - Knockdown of Nucleostemin in an ovarian cancer SKOV-3 cell line and its effects
on cell malignancy.
AB - Nucleostemin plays an essential role in the proliferation of some stem cells and
cancer cells, but no research has been conducted to assess the link between
Nucleostemin and ovarian cancer. To investigate the role of Nucleostemin in
ovarian cancer tumorigenesis, we generated short hairpin (sh)RNA to knockdown the
expression of the Nucleostemin gene in an ovarian cancer SKOV-3 cell line. We
found that knockdown of this gene led to cell-cycle arrest, as well as to an
increase in apoptosis. In addition, migration and invasion demonstrated
significant inhibition in Nucleostemin-deficient cells. Furthermore, the
knockdown of Nucleostemin dramatically suppressed xenograft progression in BALB/c
nude mice. Our findings suggest that Nucleostemin is associated with malignancy
in an ovarian cancer SKOV-3 cell line.
PMID- 28412353
TI - Crystal structure of RNA polymerase II from Komagataella pastoris.
AB - RNA polymerase II (Pol II) is a 12-subunit protein complex that conducts the
transcription of mRNA and some small RNAs. In this work, the crystal structure of
Pol II from the methylotropic yeast Komagataella pastoris (Pichia pastoris) was
determined. While the structure is highly homologous to that of Pol II from the
budding yeast Saccharomyces cerevisiae, the stalk and clamp modules of the K.
pastoris Pol II displayed large inward rotations, closing the central cleft to a
greater extent than in the known S. cerevisiae Pol II structures. The
conformational differences reflect the inherent flexibilities of the stalk and
the clamp, as additional low-resolution structures of K. pastoris Pol II in
different crystal forms revealed diverse stalk and clamp orientations.
Comparisons with other eukaryotic/archaeal RNA polymerase structures in the
Protein Data Bank revealed the distributions of the stalk and clamp orientations.
The conformational plasticity should be essential for transcriptional functions
and binding various regulatory factors.
PMID- 28412355
TI - Crystal structure of the C-terminal domain of Bacillus subtilis GabR reveals a
closed conformation by gamma-aminobutyric acid binding, inducing transcriptional
activation.
AB - Bacillus subtilis GabR (BsGabR) is involved in the gamma-aminobutyric acid (GABA)
catabolism as a transcriptional regulator, consisting of an N-terminal helix-turn
helix DNA-binding domain and a C-terminal aminotransferase-like (AT-like) domain.
Research on the C-terminal AT-like domain of BsGabR (BsGabR-CTD) has focused on
the interaction with GABA as an effector, but most its functional details remain
unclear. To understand the underlying mechanism, we report the crystal structure
of BsGabR-CTD in complex with pyridoxal 5'-phosphate (PLP) and GABA at 2.0 A
resolution. The structure of ligand-bound BsGabR-CTD revealed two distinct
monomeric states in a homodimer. One subunit is a closed-form containing the PLP
GABA adduct, and the other subunit is a PLP-bound open-form. Our structural
studies provide a detailed mechanism indicating that the open-to-closed
transition by the binding of GABA induces the conformational rearrangement of
BsGabR-CTD, which may trigger the activation of transcription.
PMID- 28412354
TI - Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign
prostatic hyperplasia.
AB - Several studies have implicated estrogen and the estrogen receptor (ER) in the
pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism
underlying this effect remains elusive. In the present study, we demonstrated
that estrogen (17beta-estradiol, or E2)-induced activation of the G protein
coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic
reticulum, increased the mitochondrial Ca2+ concentration, and thus induced
prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist
G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C
(PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by
treatment with the GPR30 antagonist G15. The release of cytochrome c and
activation of caspase-3 in response to GPR30 activation were observed. Data
generated from the analysis of animal models and human clinical samples indicate
that treatment with the GPR30 agonist relieves testosterone propionate (TP)
induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is
negatively associated with prostate volume. On the basis of these results, we
propose a novel regulatory mechanism whereby estrogen induces the apoptosis of
PECs via GPR30 activation. Inhibition of this activation is predicted to lead to
abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.
PMID- 28412357
TI - Crystal structure of Pseudomonas aeruginosa N-acetyltransferase PA4534.
AB - The GCN5-related N-acetyltransferase (GNAT) superfamily includes a large and
diverse group of enzymes that catalyzes the transfer of an acetyl group from
acetyl coenzyme A (Ac-CoA) to the amine group of a substrate. Substrates include
protein N-terminus, lysine of histone tails, and other small molecules such as
aminoglycoside, serotonin, and glucose-6-phosphate. GNAT superfamily of proteins
is involved in many physiologically important reactions in eukaryotes and
prokaryotes. However, functions of many GNATs remain unknown and PA4534 is one of
those uncharacterized GNAT proteins from Pseudomonas aeruginosa. To investigate
functions of the PA4534, we determined the apo and Ac-CoA bound PA4534
structures. Our structures showed that PA4534 shared common characteristic
structures with other GNAT family N-acetyltransferases and contained a potential
substrate binding tunnel close to the bound Ac-CoA.
PMID- 28412356
TI - Leptomycin B alters the subcellular distribution of CRM1 (Exportin 1).
AB - CRM1 (chromosome maintenance region 1, Exportin 1) binds to nuclear export
signals and is required for nucleocytoplasmic transport of a large variety of
proteins and RNP complexes. Leptomycin B (LMB), the first specific inhibitor of
CRM1 identified, binds covalently to cysteine 528 in the nuclear export signal
binding region of CRM1 leading to the inhibition of protein nuclear export.
Although the biochemical mechanisms of action of CRM1 inhibitors such as LMB are
well studied, the subcellular effects of inhibition on CRM1 are unknown. We have
found that LMB causes CRM1 to redistribute from the nucleus to the cytoplasm in
A549 cells. A significant decrease in nuclear CRM1 coupled with an increase in
cytoplasmic CRM1 was sustained for up to 4 h, while there was no change in total
CRM1 protein in fractionated cells. Cells expressing an LMB insensitive HA-tagged
CRM1-C528S protein were unaffected by LMB treatment, whereas HA-tagged wildtype
CRM1 redistributed from the nucleus to the cytoplasm with LMB treatment, similar
to endogenous CRM1. GFP-tagged CRM1 protein microinjected into the cytoplasm of
A549 cells distributed throughout the cell in untreated cells remained primarily
cytoplasmic in LMB-treated cells. Upon nuclear microinjection, GFP-CRM1
translocated to and accumulated in the cytoplasm of LMB-treated cells. Thus, LMB
binds to CRM1 and causes its redistribution to the cytoplasm by inhibiting its
nuclear import. Decreasing the nuclear availability of CRM1 likely contributes to
the accumulation of CRM1 cargo proteins in the nucleus, suggesting a new
mechanism of action for LMB.
PMID- 28412358
TI - Impact of G-quadruplex loop conformation in the PITX1 mRNA on protein and small
molecule interaction.
AB - Intramolecular G-quadruplexes (G4s) are G-rich nucleic acid structures that fold
back on themselves via interrupting loops to create stacked planar G-tetrads, in
which four guanine bases associate via Hoogsteen hydrogen bonding. The G4
structure is further stabilized by monovalent cations centered between the
stacked tetrads. The G-tetrad face on the top and bottom planes of G4s are often
the site of interaction with proteins and small molecules. To investigate the
potential impact of interrupting loops on both G4 structure and interaction with
proteins/small molecules, we characterized a specific G4 from the 3'-UTR of PITX1
mRNA that contains loops of 6 nucleotides using biophysical approaches. We then
introduced mutations to specific loops to determine the impact on G4 structure
and the ability to interact with both proteins and a G4-specific ligand. Our
results suggest that mutation of a specific loop both affects the global G4
structure and impacts the ability to interact with a G4 binding protein and small
molecule ligand.
PMID- 28412359
TI - Potentiation of docetaxel sensitivity by miR-638 via regulation of STARD10
pathway in human breast cancer cells.
AB - Acquired resistance to classical chemotherapeutics such as docetaxel (DTX)
remains a critical challenge in breast cancer (BCa) treatment. Epigenetic
modification by microRNAs (miRNAs) has been shown to play a crucial role in
cancer drug resistance. Previous study, using human drug-resistant BCa tissues,
has identified miR-638 as one of the most down-regulated miRNAs, but its exact
roles and underlying mechanisms during the pathogenesis of chemoresistance remain
to be determined. In the current study, we found that miR-638 expression was
significantly down-regulated in clinical DTX-resistant BCa tissues compared to
that in DTX-sensitive BCa tissues. By using the previously established DTX
resistant MCF-7 cells (MCF-7/R), we also confirmed that chemoresistant cells
displayed decreased levels of miR-638. To provide the direct functional evidence,
we inhibited and overexpressed miR-638 in different cell lines. Thereby, the
cells were rendered more resistant or susceptible to DTX treatment.
Mechanistically, the lipid-binding protein STARD10 was identified as a miR-638
target mediating the DTX-resistance. Hence, we provide a molecular explanation
for acquired resistance to DTX that is caused by the miR-638 deficiency and
subsequent STARD10 upregulation. In consequence, alteration of miR-638/STARD10
cascade may represent an attractive strategy in future adjuvant therapy along
with DTX chemotherapy.
PMID- 28412360
TI - In-house made nucleofection buffer for efficient and cost effective transfection
of RAW 264.7 macrophages.
AB - Electroporation is the most widely employed method of gene transfer into
macrophages which are hard to transfect. RAW 264.7 is a widely used cell line for
studying macrophage responses. Electroporation of RAW 264.7 cells with commercial
reagents although very efficient is expensive necessitating the development of
cost effective alternatives. In this study, we have formulated an economical
electroporation buffer for electroporation of RAW 264.7 cells compatible with
commercial nucleofector apparatus. We observed that supplementation of membrane
fusogenic agents such as Ficoll, PEG and membrane resealing agent, poloxamer
P188, enhanced the transfection efficiency of macrophages to a level comparable
to the commercially available solutions thereby providing us a cost effective
solution for genetic manipulation of macrophages especially in large numbers.
PMID- 28412361
TI - Structural insights into the binding mechanism of IDO1 with hydroxylamidine based
inhibitor INCB14943.
AB - IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive
enzyme, has attracted growing attention as a potential target for cancer
immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360
analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical
trials for treatment of various types of human cancer. Here, we determined the co
crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode.
INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen. Further
analysis also reveals that a halogen bonding interaction between the chlorine
atom (3-Cl) of INCB14943 and the sulphur atom of C129 significantly improves the
inhibition activity against IDO1. Comparing with the other reported inhibitors,
the oxime nitrogen and halogen bond interaction are identified as the unique
features of INCB14943 among the IDO1 inhibitors. Thus, our study provides novel
insights into the interaction between a small molecule inhibitor INCB14943 and
IDO1 protein. The structural information will facilitate future IDO1 inhibitor
design.
PMID- 28412362
TI - Probing the acidic residue within the integrin binding site of laminin-511 that
interacts with the metal ion-dependent adhesion site of alpha6beta1 integrin.
AB - Laminins are major cell-adhesive proteins of basement membranes that interact
with integrins in a divalent cation-dependent manner. Laminin-511 consists of
alpha5, beta1, and gamma1 chains, of which three laminin globular domains of the
alpha5 chain (alpha5/LG1-3) and a Glu residue in the C-terminal tail of chain
gamma1 (gamma1-Glu1607) are required for binding to integrins. However, it
remains unsettled whether the Glu residue in the gamma1 tail is involved in
integrin binding by coordinating the metal ion in the metal ion-dependent
adhesion site of beta1 integrin (beta1-MIDAS), or by stabilizing the conformation
of alpha5/LG1-3. To address this issue, we examined whether alpha5/LG1-3 contain
an acidic residue required for integrin binding that is as critical as the Glu
residue in the gamma1 tail; to achieve this, we undertook exhaustive alanine
substitutions of the 54 acidic residues present in alpha5/LG1-3 of the E8
fragment of laminin-511 (LM511E8). Most of the alanine mutants possessed
alpha6beta1 integrin binding activities comparable with wild-type LM511E8.
Alanine substitution for alpha5-Asp3198 and Asp3219 caused mild reduction in
integrin binding activity, and that for alpha5-Asp3218 caused severe reduction,
possibly resulting from conformational perturbation of alpha5/LG1-3. When alpha5
Asp3218 was substituted with asparagine, the resulting mutant possessed
significant binding activity to alpha6beta1 integrin, indicating that alpha5
Asp3218 is not directly involved in integrin binding through coordination with
the metal ion in beta1-MIDAS. Given that substitution of gamma1-Glu1607 with
glutamine nullified the binding activity to alpha6beta1 integrin, these results,
taken together, support the possibility that the critical acidic residue
coordinating the metal ion in beta1-MIDAS is Glu1607 in the gamma1 tail, but no
such residue is present in alpha5/LG1-3.
PMID- 28412363
TI - WDR5 positively regulates p53 stability by inhibiting p53 ubiquitination.
AB - WD40 repeat protein WDR5 is a core component of the Set/MLL histone
methyltransferase complex which catalyzes histone H3 Lys4 trimethylation and
activates gene transcription in human cells. WDR5 promotes Set/MLL complex
assembly and mediates the complex binding to Lys4-dimethylated histone H3 tail.
Most earlier studies report that WDR5 exerts profound effects on various cellular
and organismal processes mainly through epigenetic regulation of gene
transcription. However, the functions of WDR5 in lung cancer remain largely
unknown. Here, we report that WDR5 positively regulates p53 stability by
inhibiting p53 ubiquitination in human lung cancer A549 cells. Overexpression of
WDR5 dramatically increases p53 protein levels and its half-life in A549 cells,
while depletion of WDR5 with WDR5-specific siRNAs significantly decreases p53
protein levels. We also observe that WDR5 is required for p53 induction in
response to cisplatin treatment. Mechanistically, WDR5 colocalizes with p53 and
inhibits p53 ubiquitination, resulting in p53 stabilization. Consequently,
overexpression of WDR5 induces G1 phase arrest in A549 cells, and knocking down
WDR5 by siRNAs reduces the population at G1 phase. Furthermore, p53 expression
levels is at least in part determined by the p53 positive regulator WDR5 in some
cancer cells. Taken together, these data suggest that WDR5 is directly involved
in p53 signaling pathway. Our studies provide a new insight into WDR5 functions
in A549 cells.
PMID- 28412364
TI - The cytoplasmic translocation of Cx32 mediates cisplatin resistance in ovarian
cancer cells.
AB - Ovarian cancer is the most lethal gynecologic malignancy, and cisplatin is one of
the first-line chemotherapeutic agents. However, acquired cisplatin resistance
prevents the successful treatment of patients with ovarian cancer. Gap junction
(GJ) and connexin (Cx) are closely related to tumor formation, but the
relationship between cisplatin resistance and GJ or Cx are undetermined. In this
study, we established the cisplatin-resistant human ovarian cancer cell line
A2780-CDDP. Here we showed that cisplatin resistance was correlated to the loss
of GJ and the upregulation of Cx32 expression. Enhancing GJ in A2780-CDDP cells
could increase the apoptotic response to cisplatin treatment. Furthermore,
although Cx32 expression was increased in A2780-CDDP cells, it was more localized
to the cytoplasm rather than in the membrane, and knockdown of Cx32 in A2780-CDDP
cells sensitized them to cisplatin treatment. In summary, Cx32 is involved in
cisplatin resistance, and cytoplasmic Cx32 plays an important role in
chemoresistance.
PMID- 28412365
TI - Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by
affecting the subcellular localization of clock proteins in mammalian cells.
AB - In the eukaryotic circadian clock machinery, negative feedback repression of
CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME
(CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise
regulation of the time-dependent nuclear entry of circadian repressors is crucial
to generating normal circadian rhythms. Here, we sought to identify novel
kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased
screening using red fluorescent protein (RFP)-tagged human kinome expression
plasmids in mammalian cells. Transient expression of human vaccinia-related
kinase 3 (hVRK3) reduced the nuclear presence of mCRY1. hVRK3 expression also
induced alterations in the subcellular localization of other core clock proteins,
including mCRY2, mPER2, and BMAL1. In contrast, the subcellular localization of
mCLK was not changed. Given that singly expressed mCLK mostly resides in the
cytoplasm and that nuclear localization sequence (NLS) mutation of hVRK3
attenuated the effect of hVRK3 co-expression on subcellular localization,
ectopically expressed hVRK3 presumably reduces the retention of proteins in the
nucleus. Finally, downregulation of hvrk3 using siRNA reduced the amplitude and
lengthened the period of the cellular bioluminescence rhythm. Taken together,
these data suggest that VRK3 plays a role in setting the amplitude and period
length of circadian rhythms in mammalian cells.
PMID- 28412366
TI - NANOG gene expression is regulated by the ETS transcription factor ETV4 in human
embryonic carcinoma NCCIT cells.
AB - We demonstrated that ETV4 is a transcriptional activator of the NANOG gene in
human embryonic carcinoma NCCIT cells. The endogenous expression of NANOG and
ETV4 in naive cells was significantly down-regulated upon differentiation and by
shRNA-mediated knockdown of ETV4. NANOG transcription was significantly
upregulated by ETV4 overexpression. A putative ETS binding site (EBS) is present
in the region (-285 to -138) of the proximal promoter. Site-directed mutagenesis
of the putative EBS (-196AGGATT-191) abolished NANOG promoter activity and ETV4
interacted with this putative EBS both in vivo and in vitro. Our data provide the
molecular details of ETV4-mediated NANOG gene expression.
PMID- 28412367
TI - Deciphering antigen-responding antibody repertoires by using next-generation
sequencing and confirming them through antibody-gene synthesis.
AB - Vast diversity and high specificity of antigen recognition by antibodies are
hallmarks of the acquired immune system. Although the molecular mechanisms that
yield the extremely large antibody repertoires are precisely understood,
comprehensive description of the global antibody repertoire generated in
individual bodies has been hindered by the lack of powerful measures. To obtain
holistic understanding of the antibody-repertoire space, we used next-generation
sequencing (NGS) to analyze the deep profiles of naive and antigen-responding
repertoires of the IgM, IgG1, and IgG2c classes formed in individual mice. The
overall landscapes of naive IgM repertoires were almost the same for each mouse,
whereas those of IgG1 and IgG2c differed considerably among naive individuals.
Next, we immunized mice with a model antigen, nitrophenol (NP)-hapten linked to
chicken gamma-globulin (CGG) carrier, and compared the antigen-responding
repertoires in individual mice. To extract the complete antigen response, we
developed an intelligible method for detecting common components of antigen
responding repertoires. The major responding antibodies were IGHV1-72/IGHD1
1/IGHJ2 for NP-hapten and IGHV9-3/IGHD3-1/IGHJ2 for CGG-carrier protein. The
antigen-binding specificities of the identified antibodies were confirmed through
ELISA after antibody-gene synthesis and expression of the corresponding NGS
reads. Thus, we deciphered antigen-responding antibody repertoires by inclusively
analyzing the antibody-repertoire space generated in individual bodies by using
NGS, which avoided inadvertent omission of key antibody repertoires.
PMID- 28412368
TI - HSP90 inhibitor NVP-AUY922 induces cell apoptosis by disruption of the survivin
in papillary thyroid carcinoma cells.
AB - Heat shock protein 90 (HSP90) is a molecular chaperone required for maintaining
the stability and function of signal proteins that plays an important role in
promoting the growth and survival of cancer cells. The incidence of papillary
thyroid carcinoma (PTC) has been increasing in recent years. The effect of the
novel non-geldanamycin HSP90 inhibitor NVP-AUY922 on apoptosis of papillary
thyroid carcinoma cells has not been investigated. The influence of AUY922 on the
survival of PTC cell lines K1 and IHH4 was evaluated. Cell viability was
determined by cell counting kit method. Cell apoptosis was assessed by flow
cytometry and western blotting and the potential mechanism was evaluated by
western blotting and immunoprecipitation. Overexpression plasmid was transfected
by Lipofectamine 2000 method. In K1 and IHH4 cell lines, after the treatment of
AUY922, cell viability decreased, and the proportion of apoptosis cells
increased. AUY922 caused the cleavage of PARP and caspase-3 proteins, and altered
expression of survivin, which was a client protein of HSP90. In AUY922-treated
cells, overexpression of survivin attenuated growth inhibition and cell
apoptosis. The results indicate that AUY922 induces apoptotic cell death in PTC
cells. Moreover, our findings demonstrate that AUY922 induced apoptosis by
downregulating the expression of survivin protein in PTC cells.
PMID- 28412369
TI - Structural basis for ribosome protein S1 interaction with RNA in trans
translation of Mycobacterium tuberculosis.
AB - Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a
significant role in translation and trans-translation. In Mycobacterium
tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of
pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans
translation. However, the molecular mechanism underlying the interaction of
MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C
terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD.
NMR titration analysis revealed that the RNA binding sites on MtRpsACTD are
mainly located in the beta2, beta3 and beta5 strands and the adjacent L3 loop of
the S1 domain. Fluorescence experiments determined the MtRpsACTD binding to RNAs
are in the micromolar affinity range. Sequence analysis also revealed conserved
residues in the mapped RNA binding region. Residues L304, V305, G308, F310, H322,
I323, R357 and I358 were verified to be the key residues influencing the
interaction between MtRpsACTD and pre-sMLD. Molecular docking further confirmed
that the poly(A)-like sequence and sMLD of tmRNA are all involved in the protein
RNA interaction, through charged interaction and hydrogen bonds. The results will
be beneficial for designing new anti-tuberculosis drugs.
PMID- 28412370
TI - Suppression of adenosine monophosphate-activated protein kinase selectively
triggers apoptosis in activated T cells and ameliorates immune diseases.
AB - Deficient apoptosis of activated T cells can result in immunological disorders.
Molecules associated with energy and metabolisms are suggested to be involved in
pathogenesis of immune diseases, but remain uninvestigated. In the present study
we reported that glibenclamide exerted a new pharmacological effect on
inflammatory responses by selectively triggering apoptosis of activated T cells.
Glibenclamide demonstrated an inhibition on activated T lymphocytes, whereas
showed no toxicity in the naive cells. This effect was mainly related with its
ability to facilitate apoptosis in activated T cells with an up-regulation of
cleaved-caspases and cleaved-PARP. Glibenclamide enhanced Fas expression and
suppressed the expression of antiapoptotic cellular FLICE-inhibitory protein. The
underlying mechanism of glibenclamide was not associated with its classical
inhibitory effect on ATP-sensitive potassium channels, but due to a unique
suppression on the phosphorylation of 5' adenosine monophosphate-activated
protein kinase, which was augmented during T cell activation. An in vivo
experiment further demonstrated that glibenclamide ameliorated T-cell-mediated
contact hypersensitivity in mice. Altogether, these results suggest that AMPK
inhibition by glibenclamide can regulate the survival and death of T lymphocytes
and be beneficial for the treatment of autoimmune diseases.
PMID- 28412371
TI - The anti-inflammatory effect of tramadol in the temporomandibular joint of rats.
AB - Tramadol is a centrally acting analgesic drug able to prevent nociceptor
sensitization when administered into the temporomandibular joint (TMJ) of rats.
The mechanism underlying the peripheral anti-inflammatory effect of tramadol
remains unknown. This study demonstrated that intra-TMJ injection of tramadol
(500ug/TMJ) was able to inhibit the nociceptive response induced by 1.5% formalin
or 1.5% capsaicin, suggesting that tramadol has an antinociceptive effect, acting
directly on the primary nociceptive neurons activating the nitric oxide/cyclic
guanosine monophosphate signaling pathway. Tramadol also inhibited the
nociceptive response induced by carrageenan (100ug/TMJ) or 5-hydroxytryptamine
(225ug/TMJ) along with inhibition of inflammatory cytokines levels, leukocytes
migration and plasma extravasation. In conclusion, the results demonstrate that
peripheral administration of tramadol has a potential antinociceptive and anti
inflammatory effect. The antinociceptive effect is mediated by activation of the
intracellular nitric oxide/cyclic guanosine monophosphate pathway, at least in
part, independently from the opioid system.
PMID- 28412372
TI - Flavonoids and platelet aggregation: A brief review.
AB - Platelets are small anucleated fragments derived from a megakaryocyte precursor.
Platelets play a key role in many physiological functions especially in
hemostasis and wound healing processes in order to maintain the integrity of the
circulatory system. In addition, activated platelets release cytokines and
chemokines which modulate the immune response and, in some cases of
hyperactivation, they could be associated to the pathogenesis of inflammatory
diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known
to be potent antioxidants with positive effects against diverse diseases such as
cancer, neurodegenerative or cardiovascular disease. It has been reported that
some flavonoids possess anti-platelet aggregation effects though different
pathways, being the inhibition of the arachidonic acid-based pathway the most
representative mechanism of action. In the present review, the main sources of
flavonoids, as well as their bioavailability and metabolism are summarized.
Moreover, the available data about the anti-aggregation effects of flavonoids and
the different mechanisms of action that has been proposed until now are also
discussed.
PMID- 28412373
TI - Mechanistic evaluation of tapentadol in reducing the pain perception using in
vivo brain and spinal cord microdialysis in rats.
AB - Role of monoamine neurotransmitters in the modulation of emotional and pain
processing in spinal cord and brain regions is not well known. Tapentadol, a
norepinephrine reuptake inhibitor with u-opioid receptor agonistic activity has
recently been introduced for the treatment of moderate to severe pain. The
objective of the present study was to examine the effects of tapentadol on
modulation of monoamines in the prefrontal cortex and dorsal horn using brain
microdialysis. Tapentadol was administered intraperitoneally at 4.64-21.5mg/kg to
male Wistar rats. Based on these results, 10mg/kg i.p. was chosen for spinal
microdialysis in freely moving rats. Tapentadol produced significant and dose
dependent increase in cortical dopamine and norepinephrine levels with mean
maximum increase of 600% and 300%, respectively. Treatment had no effect on
cortical serotonin levels. In the dorsal horn, serotonin, dopamine and
norepinephrine levels were significantly increased with mean maximum increases of
220%, 190% and 280%, respectively. Although the density of dopamine transporter
is low in cortex, the increase of dopamine and norepinephrine levels in cortex
could be mediated through the inhibition of norepinephrine transporter. In the
dorsal horn, increase in norepinephrine levels could be due to inhibition of
norepinephrine transporter in the spinal cord. Whereas, activation of opioids
receptors in non-spinal regions might be responsible for increase in dopamine and
serotonin levels. The results from current investigation suggest that clinical
efficacy of tapentadol in neuropathic pain is mediated through the enhanced
monoaminergic neurotransmission in the spinal cord and regions involved with
emotional processing in brain.
PMID- 28412374
TI - A novel mitochondrial ATP6 frameshift mutation causing isolated complex V
deficiency, ataxia and encephalomyopathy.
AB - We describe a novel frameshift mutation in the mitochondrial ATP6 gene in a 4
year-old girl associated with ataxia, microcephaly, developmental delay and
intellectual disability. A heteroplasmic frameshift mutation in the MT-ATP6 gene
was confirmed in the patient's skeletal muscle and blood. The mutation was not
detectable in the mother's DNA extracted from blood or buccal cells. Enzymatic
and oxymetric analysis of the mitochondrial respiratory system in the patients'
skeletal muscle and skin fibroblasts demonstrated an isolated complex V
deficiency. Native PAGE with subsequent immunoblotting for complex V revealed
impaired complex V assembly and accumulation of ATPase subcomplexes. Whilst
northern blotting confirmed equal presence of ATP8/6 mRNA, metabolic 35S
labelling of mitochondrial translation products showed a severe depletion of the
ATP6 protein together with aberrant translation product accumulation. In
conclusion, this novel isolated complex V defect expands the clinical and genetic
spectrum of mitochondrial defects of complex V deficiency. Furthermore, this work
confirms the benefit of native PAGE as an additional diagnostic method for the
identification of OXPHOS defects, as the presence of complex V subcomplexes is
associated with pathogenic mutations of mtDNA.
PMID- 28412377
TI - What Can we Learn (and What Can't we Learn) from Observational Studies of
Adolescent Varicocele Treatment?
PMID- 28412378
TI - Project management: importance for diagnostic laboratories.
AB - BACKGROUND: The need for diagnostic laboratories to improve both quality and
productivity alongside personnel shortages incite laboratory managers to
constantly optimize laboratory workflows, organization, and technology. These
continuous modifications of the laboratories should be conducted using efficient
project and change management approaches to maximize the opportunities for
successful completion of the project. AIM: This review aims at presenting a
general overview of project management with an emphasis on selected critical
aspects. SOURCES: Conventional project management tools and models, such as
HERMES, described in the literature, associated personal experience, and
educational courses on management have been used to illustrate this review.
CONTENT: This review presents general guidelines of project management and
highlights their importance for microbiology diagnostic laboratories. As an
example, some critical aspects of project management will be illustrated with a
project of automation, as experienced at the laboratories of bacteriology and
hygiene of the University Hospital of Lausanne. It is important to define clearly
beforehand the objective of a project, its perimeter, its costs, and its time
frame including precise duration estimates of each step. Then, a project
management plan including explanations and descriptions on how to manage,
execute, and control the project is necessary to continuously monitor the
progression of a project to achieve its defined goals. Moreover, a thorough risk
analysis with contingency and mitigation measures should be performed at each
phase of a project to minimize the impact of project failures. IMPLICATIONS: The
increasing complexities of modern laboratories mean clinical microbiologists must
use several management tools including project and change management to improve
the outcome of major projects and activities.
PMID- 28412379
TI - Challenges of measles and rubella laboratory diagnostic in the era of
elimination.
AB - The Member States of the WHO European Region adopted the goal of measles and
rubella elimination more than 10 years ago, but so far only 21 of 53 countries
have reached this target. Laboratory investigation of suspected cases is
essential to support disease elimination efforts. Therefore, WHO maintains a
network of accredited laboratories providing high-quality testing. Laboratory
investigation heavily relies on specific IgM serology and increasingly on virus
detection by reverse transcription (RT)-PCR, but other methods such as IgG
avidity testing and genetic characterization of virus strains have gained in
importance. In elimination settings, often few samples from suspected cases are
available for testing, but testing proficiency must be maintained. The predictive
value of an IgM-positive result decreases and other rash-fever disease
aetiologies become more important. In addition, cases with a rash after
measles/rubella vaccination or with mild disease after waning of vaccine-induced
antibodies are seen more often. Thus, it is necessary to perform comprehensive
and potentially time-consuming and costly investigations of every suspected case
using quality-controlled laboratory methods. At the same time rapid feedback to
public health officers is required for timely interventions. The introduction of
new laboratory methods for comprehensive case investigations requires training of
staff under the supervision of WHO-accredited reference laboratories and the
definition of appropriate test algorithms. Clinical, laboratory, and
epidemiological data are essential for final case classification and
investigation of chains of transmission in the endgame of measles and rubella
elimination.
PMID- 28412380
TI - Colonization by multidrug-resistant organisms in long-term care facilities in
Italy: a point-prevalence study.
AB - OBJECTIVES: To determine prevalence and risk factors for colonization by
multidrug-resistant organisms (MDROs) in long-term care facility (LTCF) residents
in Italy. Genotypes of MDRO isolates were investigated. METHODS: A point
prevalence study was conducted at 12 LTCFs located in four Italian cities (2
February to 14 March 2015). Rectal swabs, faeces and nasal/auxiliary swabs were
cultured for extended-spectrum beta-lactamase (ESBL)- and/or carbapenemase
producing Enterobacteriaceae, Clostridium difficile and methicillin-resistant
Staphylococcus aureus (MRSA) respectively. Antimicrobial susceptibility testing,
detection of ESBL and/or carbapenemase genes and molecular typing of MDROs were
performed. Risk factors for colonization were determined by univariate and
multivariate analysis. RESULTS: A total of 489 LTCF residents aged >=65 years
were enrolled. The prevalence of colonization by ESBL-producing
Enterobacteriaceae, MRSA and C. difficile was 57.3% (279/487), 17.2% (84/487) and
5.1% (21/409) respectively. Carriage rate of carbapenemase-producing
Enterobacteriaceae was 1% (5/487). Being bedridden was a common independent risk
factor for colonization by all MDROs, although risk factors specific for each
MDRO were identified. ESBL-producing Escherichia coli carriage was associated
with the sequence type (ST) 131-H30 subclone, but other minor STs predominated in
individual LTCF or in LTCFs located in the same city, suggesting a role for
intrafacility or local transmission. Similarly, MRSA from LTCF residents belonged
to the same spa types/ST clones (t008/ST8 and t032/ST22) commonly found in
Italian acute-care hospitals, but infrequent spa types were recovered in
individual LTCFs. The prevalent C. difficile PCR ribotypes were 356/607 and 018,
both common in Italian acute-care hospitals. CONCLUSIONS: MDRO colonization is
common among residents in Italian LTCFs.
PMID- 28412381
TI - Optimal efficacy of interferon-free HCV retreatment after protease inhibitor
failure in real life.
AB - OBJECTIVES: First-generation protease-inhibitors (PIs) have suboptimal efficacy
in GT-1 patients with advanced liver disease, and patients experiencing treatment
failure may require urgent retreatment. Our objective was to analyse the real
life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role
of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In
this multi-centre observational study, patients retreated with IFN-free regimens
after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were
included. Sustained-virological-response (SVR) was evaluated at week 12 of follow
up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121
patients (cirrhotic=86.8%) were retreated following three different strategies:
A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT
guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens
(N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided'
regimens reached SVR (100%), despite heterogeneity in treatment duration, use of
PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL
recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the
31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01).
Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a
cirrhotic patients failed an option (C) simeprevir-containing treatment; three
out of four had a baseline R155K NS3-RAS. All seven patients treated with
paritaprevir-containing regimens reached SVR, regardless of treatment duration
and performance of a baseline-GRT. CONCLUSION: Retreatment of PI-experienced
patients can induce maximal SVR rates in real life. Baseline-GRT could help to
optimize retreatment strategy, allowing PIs to be reconsidered when chosen after
a RASs evaluation.
PMID- 28412382
TI - Use of nebulized antimicrobials for the treatment of respiratory infections in
invasively mechanically ventilated adults: a position paper from the European
Society of Clinical Microbiology and Infectious Diseases.
AB - With an established role in cystic fibrosis and bronchiectasis, nebulized
antibiotics are increasingly being used to treat respiratory infections in
critically ill invasively mechanically ventilated adult patients. Although there
is limited evidence describing their efficacy and safety, in an era when there is
a need for new strategies to enhance antibiotic effectiveness because of a
shortage of new agents and increases in antibiotic resistance, the potential of
nebulization of antibiotics to optimize therapy is considered of high interest,
particularly in patients infected with multidrug-resistant pathogens. This
Position Paper of the European Society of Clinical Microbiology and Infectious
Diseases provides recommendations based on the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) methodology regarding the use of
nebulized antibiotics in invasively mechanically ventilated adults, based on a
systematic review and meta-analysis of the existing literature (last search July
2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in
clinical practice, due to a weak level of evidence of their efficacy and the high
potential for underestimated risks of adverse events (particularly, respiratory
complications). Higher-quality evidence is urgently needed to inform clinical
practice. Priorities of future research are detailed in the second part of the
Position Paper as guidance for researchers in this field. In particular, the
panel identified an urgent need for randomized clinical trials of nebulized
antibiotic therapy as part of a substitution approach to treatment of pneumonia
due to multidrug-resistant pathogens.
PMID- 28412384
TI - Molecular epidemiology of penicillinase-producing Neisseria gonorrhoeae isolates
in France.
AB - OBJECTIVES: Characterizing the molecular epidemiology of antibiotic resistance is
crucial for a better understanding of the evolution and spread of resistance in
Neisseria gonorrhoeae. Here, we examine the molecular epidemiology of
penicillinase-producing N. gonorrhoeae (PPNG) isolates in France. METHODS: We
investigated 176 PPNG isolates collected between 2010 and 2012 by the National
Reference Centre in France. Genotyping was performed using the NG-MAST technique,
blaTEM genes were Sanger-sequenced, and plasmids were characterized by PCR
typing. RESULTS: We revealed the existence of four major clusters representing
about one-third of PPNG circulating in France. These clusters were related to
ST1479 (18/176, 10.2%), to ST1582 (15/176, 8.5%), to ST8922 (10/176, 5.6%), and
to ST1285 (9/176, 5.1%). Wild-type TEM-1 was identified in 151 (151/176, 85.8%)
PPNG isolates, and TEM-1 variants were mostly represented by the M182T mutation
(14/176, 8%), followed by P14S/L (8/176, 4.5%), G228S (2/176, 1.1%), and Q269K
(1/176, 0.6%). The blaTEM genes were carried by African (157/176, 89.2%), Asian
(13/176, 7.4%), and Toronto/Rio (6/176, 3.4%) plasmids. The M182T variants were
found in various genetic backgrounds, whereas the P14S variants were disseminated
clonally. The G228S and Q269K variants belong to one of the four major clusters
of PPNG, which suggests a recent de novo emergence of these mutations.
CONCLUSIONS: Our results show that approximately one-third of the penicillinase
producing N. gonorrhoeae isolates in France belong to one of four major clusters
and that the spread of the different TEM variants is associated with distinct
patterns of molecular epidemiology.
PMID- 28412383
TI - A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM
joint study.
AB - OBJECTIVES: A prospective international multicentre surveillance study was
conducted to investigate the prevalence and amphotericin B susceptibility of
Aspergillus terreus species complex infections. METHODS: A total of 370 cases
from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus
species complex among the investigated patients with mould-positive cultures was
5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8
mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide
spectrum of aspergillosis and the majority of cryptic species display high
amphotericin B MICs.
PMID- 28412385
TI - Eliminating measles and rubella in Europe.
PMID- 28412386
TI - Characterization of rodent constitutively active estrogen receptor alpha variants
and their constitutive transactivation mechanisms.
AB - Estrogen receptor alpha (ERalpha) mRNAs exhibit remarkable heterogeneity owing to
complicated alternative splicing. Some encode C-terminally-truncated ERalpha
proteins, which display ligand-independent transactivation or dominant-negative
activity. We previously characterized C-terminally-truncated ERalpha mRNA
variants with cryptic sequences in humans and mice, and demonstrated that helices
in the ligand-binding domains (LBDs) of ERalpha variants contribute to ligand
independent transcriptional activity. However, existence of non-conventional
coding exons and generation of constitutively active ERalpha variants have
remained to be examined in rats. To comparatively analyze modular organization
and splicing profiles of the ERalpha genes, the range of C-terminally-truncated
ERalpha variants was explored in rats and mice using rapid amplification of cDNA
ends and RT-PCR cloning. Furthermore, their functions were determined in
transiently transfected cells using expression constructs and luciferase reporter
assays. Multiple cryptic exons and C-terminally-truncated ERalpha variant mRNAs
were identified in rats and mice. Naturally occurring and artificially truncated
variants/constructs lacking helix 5 potentially exhibited gain-of-function in
transfected cells. Although cryptic exons and splicing profiles were poorly
conserved among humans, mice, and rats, constitutively active variants were
generated from the ERalpha genes. Moreover, the primary mechanism of ligand
independent activation by C-terminally-truncated ERalpha variants is C-terminus
to helix 5 deletion in the LBD. This comparative study documented the complexity
of ERalpha genes, mRNAs, and proteins, and further determined the underlying
structural basis of ligand-independent activation by C-terminally-truncated
ERalpha variants.
PMID- 28412387
TI - Germ cells regulate 3-hydroxybutyrate production in rat Sertoli cells.
AB - Paracrine regulation of Sertoli cell function by germ cells is an outstanding
characteristic of testicular physiology. It has been demonstrated that Sertoli
cells produce ketone bodies and that germ cells may use them as energy source.
The aim of the study was to analyze a possible regulation by germ cells of
ketogenesis in Sertoli cells. Cultures of Sertoli cells (SC) obtained from 31-day
old rats were co-cultured with germ cells (GC). The results presented herein show
that the presence of GC stimulated 3-hydroxybutyrate production and increased
mRNA levels of two enzymes involved in ketogenesis-carnitine palmitoyltransferase
1a (CPT1a) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (mHMGCoA) synthase-
in SC. Additionally, GC increased monocarboxylate transporter 4 (Mct4) expression
in SC, a transporter involved in ketone bodies exit. To evaluate if the observed
effects might be mediated by soluble factors, SC cultures were incubated with
germinal cell-conditioned medium (GCCM) or with two growth factors, bFGF and
IGF1, which are known to be secreted by GC. We observed that GCCM and bFGF
stimulated ketone bodies production but that IGF1 did not modify it. Also, we
observed that GCCM and bFGF increased Cpt1a and Mct4 mRNA levels. In summary,
results presented herein demonstrate that Sertoli cells are able to produce
ketone bodies and that its production is regulated in a paracrine way by germ
cells. This study adds new information about communication between Sertoli cells
and developing germ cells.
PMID- 28412388
TI - Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus
sphinx during delayed embryonic development.
AB - The aim of this study was to evaluate the role of prolactin as a modulator of
luteal steroidogenesis during the period of delayed embryonic development in
Cynopterus sphinx. A marked decline in circulating prolactin levels was noted
during the months of November through December coinciding with the period of
decreased serum progesterone and delayed embryonic development. The seasonal
changes in serum prolactin levels correlated positively with circulating
progesterone (P) level, but inversely with circulating melatonin level during
first pregnancy showing delayed development in Cynopterus sphinx. The results
also showed decreased expression of prolactin receptor-short form (PRL-RS) both
in the corpus luteum and in the utero-embryonic unit during the period of delayed
embryonic development. Bats treated in vivo with prolactin during the period of
delayed development showed significant increase in serum progesterone and
estradiol levels together with significant increase in the expression of PRL-RS,
luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR)
and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the ovary. Prolactin
stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell
survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian
progesterone production and the expression of prolactin-receptor, LH-R, STAR and
3beta-HSD proteins were noted following the exposure of LH or prolactin in vitro
during the delayed period. In conclusion, short-day associated increased
melatonin level may be responsible for decreased prolactin release during
November-December. The decline in prolactin level might play a role in
suppressing P and estradiol-17beta (E2) estradiol levels thereby causing delayed
embryonic development in C. sphinx.
PMID- 28412389
TI - Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic
Stents.
AB - BACKGROUND: Recent evidence suggests that bioresorbable vascular scaffolds (BVS)
are associated with an excess of thrombotic complications compared with metallic
everolimus-eluting stents (EES). OBJECTIVES: This study sought to investigate the
comparative effectiveness of the Food and Drug Administration-approved BVS versus
metallic EES in patients undergoing percutaneous coronary intervention at longest
available follow-up. METHODS: The authors searched MEDLINE, Scopus, and web
sources for randomized trials comparing BVS and EES. The primary efficacy and
safety endpoints were target lesion failure and definite or probable stent
thrombosis, respectively. RESULTS: Seven trials were included: in sum, 5,583
patients were randomized to receive either the study BVS (n = 3,261) or the EES
(n = 2,322). Median time of follow-up was 2 years (range 2 to 3 years). Compared
with metallic EES, risk of target lesion failure (9.6% vs. 7.2%; absolute risk
difference: +2.4%; risk ratio: 1.32; 95% confidence interval: 1.10 to 1.59;
number needed to harm: 41; p = 0.003; I2 = 0%) and stent thrombosis (2.4% vs.
0.7%; absolute risk difference: +1.7%; risk ratio: 3.15; 95% confidence interval:
1.87 to 5.30; number needed to harm: 60; p < 0.0001; I2 = 0%) were both
significantly higher with BVS. There were no significant differences in all-cause
or cardiovascular mortality between groups. The increased risk for ST associated
with BVS was concordant across the early (<30 days), late (30 days to 1 year),
and very late (>1 year) periods (pinteraction = 0.49). CONCLUSIONS: Compared with
metallic EES, the BVS appears to be associated with both lower efficacy and
higher thrombotic risk over time. (Bioresorbable vascular scaffold compare to
everolimus stents in long term follow up; CRD42017059993).
PMID- 28412390
TI - First-Generation Bioresorbable Vascular Scaffolds: Disappearing Stents or
Disappearing Evidence?
PMID- 28412391
TI - Moving toward endotypes in atopic dermatitis: Identification of patient clusters
based on serum biomarker analysis.
AB - BACKGROUND: Atopic dermatitis (AD) is a complex, chronic, inflammatory skin
disease with a diverse clinical presentation. However, it is unclear whether this
diversity exists at a biological level. OBJECTIVE: We sought to test the
hypothesis that AD is heterogeneous at the biological level of individual
inflammatory mediators. METHODS: Sera from 193 adult patients with moderate-to
severe AD (six area, six sign atopic dermatitis [SASSAD] score: geometric mean,
22.3 [95% CI, 21.3-23.3] and 39.1 [95% CI, 37.5-40.9], respectively) and 30
healthy control subjects without AD were analyzed for 147 serum mediators, total
IgE levels, and 130 allergen-specific IgE levels. Population heterogeneity was
assessed by using principal component analysis, followed by unsupervised k-means
cluster analysis of the principal components. RESULTS: Patients with AD showed
pronounced evidence of inflammation compared with healthy control subjects.
Principal component analysis of data on sera from patients with AD revealed the
presence of 4 potential clusters. Fifty-seven principal components described
approximately 90% of the variance. Unsupervised k-means cluster analysis of the
57 largest principal components delivered 4 distinct clusters of patients with
AD. Cluster 1 had high SASSAD scores and body surface areas with the highest
levels of pulmonary and activation-regulated chemokine, tissue inhibitor of
metalloproteinases 1, and soluble CD14. Cluster 2 had low SASSAD scores with the
lowest levels of IFN-alpha, tissue inhibitor of metalloproteinases 1, and
vascular endothelial growth factor. Cluster 3 had high SASSAD scores with the
lowest levels of IFN-beta, IL-1, and epithelial cytokines. Cluster 4 had low
SASSAD scores but the highest levels of the inflammatory markers IL-1, IL-4, IL
13, and thymic stromal lymphopoietin. CONCLUSION: AD is a heterogeneous disease
both clinically and biologically. Four distinct clusters of patients with AD have
been identified that could represent endotypes with unique biological mechanisms.
Elucidation of these endotypes warrants further investigation and will require
future intervention trials with specific agents, such as biologics.
PMID- 28412392
TI - Diminished airway macrophage expression of the Axl receptor tyrosine kinase is
associated with defective efferocytosis in asthma.
PMID- 28412393
TI - Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein
kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) signaling pathway, which is
counterregulated by autophagy.
AB - BACKGROUND: Eosinophils are a subset of granulocytes that can be involved in the
pathogenesis of different diseases, including allergy. Their effector functions
are closely linked to their cytotoxic granule proteins. Release takes place
through several different mechanisms, one of which is cytolysis, which is
associated with release of intact granules, so-called clusters of free eosinophil
granules. The mechanism underlying this activation-induced form of cell death in
eosinophils has remained unclear. OBJECTIVE: We aimed to elucidate the molecular
mechanism of eosinophil cytolysis. METHODS: Isolated blood eosinophils were
incubated on glass coverslips coated with intravenous immunoglobulin and inactive
complement component 3b. A morphologic characterization of the distinct stages of
the proposed cascade was addressed by means of time-lapse automated fluorescence
microscopy, electron microscopy, and immunohistochemistry. Experiments with
pharmacologic inhibitors were performed to elucidate the sequence of events
within the cascade. Tissue samples of patients with eosinophilic skin diseases or
eosinophilic esophagitis were used for in vivo analyses. RESULTS: After
eosinophil adhesion, we observed reactive oxygen species production, early
degranulation, and granule fusion processes, leading to a distinct morphology
exhibiting cytoplasmic vacuolization and, finally, cytolysis. Using a
pharmacologic approach, we demonstrate the presence of a receptor-interacting
protein kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) signaling pathway in
eosinophils, which, after its activation, leads to the production of high levels
of reactive oxygen species in a p38 mitogen-activated protein kinase and
phosphatidylinositol 3'-kinase-dependent manner. All these steps are required for
cytoplasmic vacuolization and subsequent cytolysis to occur. Interestingly,
triggering cytolysis is associated with an induction of autophagy in eosinophils,
and additional stimulation of autophagy by means of pharmacologic inhibition of
the mechanistic target of rapamycin counterregulates cell death. Moreover, MLKL
phosphorylation, cytoplasmic vacuolization, and cytolysis were observed in
eosinophils under in vivo inflammatory conditions. CONCLUSION: We report that
adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent
necroptosis, which can be counterregulated by autophagy.
PMID- 28412394
TI - Water-soluble chitosan inhibits nerve growth factor and attenuates allergic
inflammation in mite allergen-induced allergic rhinitis.
PMID- 28412395
TI - Severe asthma: Differential chemokine response of airway epithelial cells.
PMID- 28412396
TI - Systems approach to uncover signaling networks in primary immunodeficiency
diseases.
PMID- 28412397
TI - Caveat on the Boltzmann distribution function use in biology.
AB - Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become
extremely popular to describe diverse biological situations. Part of the
popularity is due to the easy availability of software which fits Boltzmann
functions to data, without much knowledge of the fitting procedure or the
statistical properties of the parameters derived from the procedure. The purpose
of this paper is to explore the plasticity of the Boltzmann function to fit data,
some aspects of the optimization procedure to fit the function to data and how to
use this plastic function to differentiate the effect of treatment on data and to
attest the statistical significance of treatment effect on the data.
PMID- 28412398
TI - Recent Update on Nanoemulgel as Topical Drug Delivery System.
AB - Being an emerging transdermal delivery tool, nanoemulgel, has proved to show
surprising upshots for the lipophilic drugs over other formulations. This
lipophilic nature of majority of the newer drugs developed in this modern era
resulting in poor oral bioavailability, erratic absorption, and pharmacokinetic
variations. Therefore, this novel transdermal delivery system has been proved to
be advantageous over other oral and topical drug delivery to avoid such
disturbances. These nanoemulgels are basically oil-in-water nanoemulsions gelled
with the use of some gelling agent in it. This gel phase in the formulation is
nongreasy, which favors user compliance and stabilizes the formulation through
reduction in surface as well as interfacial tension. Simultaneously, it can be
targeted more specifically to the site of action and can avoid first-pass
metabolism and relieve the user from gastric/systemic incompatibilities. This
brief review is focused on nanoemulgel as a better topical drug delivery system
including its components screening, formulation method, and recent
pharmacokinetic and pharmacodynamic advancement in research studies carried out
by the scientists all over the world. Therefore, at the end of this survey it
could be inferred that nanoemulgel can be a better and effective drug delivery
tool for the topical system.
PMID- 28412399
TI - Quantitative Component Analysis of Solid Mixtures by Analyzing Time Domain 1H and
19F T1 Saturation Recovery Curves (qSRC).
AB - Prevalent polymorphism and complicated phase behavior of active pharmaceutical
ingredients (APIs) often result in remarkable differences in the respective
biochemical and physical API properties. Consequently, API form characterization
and quantification play a central role in the pharmaceutical industry from early
drug development to manufacturing. Here we present a novel and proficient
quantification protocol for solid mixtures (qSRC) based on the measurement and
mathematical fitting of T1 nuclear magnetic resonance (NMR) saturation recovery
curves collected on a bench top time-domain NMR instrument. The saturation
recovery curves of the relevant pure components are used as fingerprints.
Employing a bench top NMR instrument possesses clear benefits. These instruments
exhibit a small footprint, do not present any special requirements on lab space,
and required sample handling is simple and fast. The qSRC analysis can easily be
conducted in a conventional laboratory setting as well as in an industrial
production environment, making it a versatile tool with the potential for
widespread application. The accuracy and efficiency of the qSRC method is
illustrated using 1H and 19F T1 data of selected pharmaceutical model compounds,
as well as utilizing 1H T1 data of an actual binary API anhydrous polymorph
system of a Merck & Co., Inc. compound formerly developed as a hepatitis C virus
drug.
PMID- 28412400
TI - Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following
Losartan Administration Using Static and Physiologically Based Pharmacokinetic
Models.
AB - The aim of this study was to evaluate a strategy based on static and dynamic
physiologically based pharmacokinetic (PBPK) modeling for the prediction of
metabolite and parent drug area under the time-concentration curve ratio
(AUCm/AUCp) and their PK profiles in humans using in vitro data when active
transport processes are involved in disposition. The strategy was applied to
losartan and its pharmacologically active metabolite carboxylosartan as test
compounds. Hepatobiliary transport including transport-mediated uptake,
canilicular and basolateral efflux, and metabolic clearance estimates were
obtained from in vitro studies using human liver microsomes and sandwich-cultured
hepatocytes. Human renal clearance of carboxylosartan was estimated from dog
renal clearance using allometric scaling approach. All clearance mechanisms were
mechanistically incorporated in a static model to predict the relative exposure
of carboxylosartan versus losartan (AUCm/AUCp). The predicted AUCm/AUCp were
consistent with the observed data following intravenous and oral administration
of losartan. Moreover, the in vitro parameters were used as initial parameters in
PBPK permeability-limited disposition models to predict the concentration-time
profiles for both parent and its active metabolite after oral administration of
losartan. The PBPK model was able to recover the plasma profiles of both losartan
and carboxylosartan, further substantiating the validity of this approach.
PMID- 28412401
TI - Proteasome Inhibitor-Loaded Micelles Enhance Antitumor Activity Through
Macrophage Reprogramming by NF-kappaB Inhibition.
AB - Macrophage reprogramming toward a tumor-attacking phenotype is a promising
treatment strategy, yet such strategies are scarce and it is not clear how to
combine them with cytotoxic therapies that are often used to treat solid tumors.
Here, we evaluate whether a micelle-encapsulated proteasome inhibitor, that is,
the peptide aldehyde drug MG132, which is cytotoxic to cancer cells, can
reprogram macrophages to attack the tumor. Through in vitro studies, we
demonstrated that the proteasome inhibition reduces nuclear factor kappa-light
chain-enhancer of activated B cells (NF-kappaB) signaling-a known promoter of
tumor-supporting macrophages and chemoresistance-in both cancer cells and
macrophages. In in vivo studies, we showed that, although free MG132 did not
affect the macrophage phenotype in tumors even at its maximum tolerated dose, the
micellar formulation of MG132 safely achieved simultaneous cancer cell killing
and macrophage reprogramming, thereby enhancing the antitumor efficacy in a
syngeneic, orthotopic breast cancer model.
PMID- 28412402
TI - Flavonoid composition of orange peel extract ameliorates alcohol-induced tight
junction dysfunction in Caco-2 monolayer.
AB - Dry citrus peels, also known as "chenpi", have been traditionally used to treat
and relieve intestinal inflammation. Recently we have reported that orange peel
extracts (OPE) which contain relatively greater polymethoxylated flavone (PMF)
content exhibit superior antioxidant and anti-inflammatory activities in vitro.
Moreover, these bioactivities were notably greater than an equivalent flavonoid
mixture (FM). The present study compares the effects of different OPE sources
with distinct PMF composition on tight junction (TJ) dysfunction induced by
ethanol. The OPE obtained from Xinhui, China, contained a 20-fold higher PMF
content than extracts derived from the orange peels sourced from Guangxi. Xinhui
OPE treatment of ethanol treated Caco-2 cells corresponded to lower (P < 0.05)
lactate dehydrogenase (LDH) leakage and higher (P < 0.05) glutathione reductase
activity. Both OPE and the FM prevented ethanol-induced increases in Caco-2 cell
paracellular permeability and the dislocation of TJ proteins, including claudin
4, occludin, and zonulin occludin-1 (ZO-1), respectively. Xinhui-OPE increased
the expression of claudin 4 and occludin protein, but not mRNA, whereas, Guangxi
OPE and Xinhui-FM had no effect on TJ protein expression. In conclusion, OPE
derived from sources that contain higher concentrations of PMF are more effective
at preventing intestinal barrier dysfunction of TJ proteins induced by ethanol.
PMID- 28412403
TI - A further development of the QNAR model to predict the cellular uptake of
nanoparticles by pancreatic cancer cells.
AB - Nanotechnology has led to the development of new nanomaterials with unique
properties and a wide variety of applications. In the present study, we focused
on the cellular uptake of a group of nanoparticles with a single metal core by
pancreatic cancer cells, which has been studied by Yap et al. (Rsc Advances,
2012, 2 (2):8489-8496) using classification models. In this work, the development
of a further Quantitative Nanostructure-Activity Relationship (QNAR) model was
performed by linear multiple linear regression (MLR) and nonlinear artificial
neural network (ANN) techniques to accurately predict the cellular uptake values
of these compounds by dividing them into three groups. Judging from the attained
statistical results, our derived QNAR models have an acceptable overall accuracy
and robustness, as well as good predictivity on the external data sets. Moreover,
the results of this study provide some insights on how engineered nanomaterial
features influence cellular responses and thereby outline possible approaches for
developing and applying predictive computational models for biological responses
caused by exposure to nanomaterials.
PMID- 28412404
TI - Development of human biotransformation QSARs and application for PBT assessment
refinement.
AB - Toxicokinetics heavily influence chemical toxicity as the result of Absorption,
Distribution, Metabolism (Biotransformation) and Elimination (ADME) processes.
Biotransformation (metabolism) reactions can lead to detoxification or, in some
cases, bioactivation of parent compounds to more toxic chemicals. Moreover,
biotransformation has been recognized as a key process determining chemical half
life in an organism and is thus a key determinant for bioaccumulation assessment
for many chemicals. This study addresses the development of QSAR models for the
prediction of in vivo whole body human biotransformation (metabolism) half-lives
measured or empirically-derived for over 1000 chemicals, mainly represented by
pharmaceuticals. Models presented in this study meet regulatory standards for
fitting, validation and applicability domain. These QSARs were used, in
combination with literature models for the prediction of biotransformation half
lives in fish, to refine the screening of the potential PBT behaviour of over
1300 Pharmaceuticals and Personal Care Products (PPCPs). The refinement of the
PBT screening allowed, among others, for the identification of PPCPs, which were
predicted as PBTs on the basis of their chemical structure, but may be easily
biotransformed. These compounds are of lower concern in comparison to potential
PBTs characterized by large predicted biotransformation half-lives.
PMID- 28412405
TI - Consumption and exposure assessment to cosmetic products for children under 2
years old.
AB - Today, the use of personal care products is an integral part of daily life.
Little information about children's consumption and exposure to cosmetic products
is available. The aim of the study was to assess the consumption and the exposure
of French babies aged 0-23 months old to seven common baby care products:
shampoo, shower gel, cleansing water, cleansing milk, moisturizing cream, bottom
cream and wipes. Consumption and exposure were assessed using small age intervals
in order to identify any differences. Exposure was calculated using a
probabilistic method. These original data will be useful for safety assessors and
safety agencies in order to protect consumers.
PMID- 28412406
TI - Chemical toxicity prediction for major classes of industrial chemicals: Is it
possible to develop universal models covering cosmetics, drugs, and pesticides?
AB - Computational models have earned broad acceptance for assessing chemical toxicity
during early stages of drug discovery or environmental safety assessment. The
majority of publicly available QSAR toxicity models have been developed for
datasets including mostly drugs or drug-like compounds. We have evaluated and
compared chemical spaces occupied by cosmetics, drugs, and pesticides, and
explored whether current computational models of toxicity endpoints can be
universally applied to all these chemicals. Our analysis of the chemical space
overlap and applicability domain (AD) of models built previously for twenty
different toxicity endpoints showed that most of these models afforded high
coverage (>90%) for all three classes of compounds analyzed herein. Only T.
pyriformis models demonstrated lower coverage for drugs and pesticides (38% and
54%, respectively). These results show that, for the most part, historical QSAR
models built with data available for different toxicity endpoints can be used for
toxicity assessment of novel chemicals irrespective of the intended commercial
use; however, the AD restriction is necessary to assure the expected prediction
accuracy. Local models may need to be developed to capture chemicals that appear
as outliers with respect to global models.
PMID- 28412407
TI - Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella
pneumoniae strains producing carbapenemases in an Italian teaching hospital from
January 2015 to September 2016.
AB - OBJECTIVES: We described Klebsiella pneumoniae producing carbapenemase (CPKP)
spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. METHODS: The
first positive surveillance rectal swab (SRS) or clinical sample (CS) collected
in the medical department (MD), surgical department (SD) and intensive care
department (ICD) were included in the study. A validated in-house Real-Time PCR
method was used to detect carbapenemases; multilocus sequence typing (MLST) was
used for further characterization of the strains. RESULTS: 21535 patients were
included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from
clinical samples (CS) were collected. The percentage of CPKP detected in SRS with
respect to CS increased in the medical MD from 2015 to 2016 (p=0.01) and in ICD
from 2012 to 2015 (p=0.0001), while it decreased in SD from 2014 to 2016
(p=0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more
frequently identified in CS than in SRS in MD. Twelve strains harboured more than
one carbapenemase gene. Many other species harbouring a carbapenemase gene were
collected. CONCLUSIONS: MDs need more inclusive surveillance criteria. The late
detection of positive SRS underlined the risk of colonization during
hospitalization.
PMID- 28412408
TI - Breast abscess due to Bacillus Calmette-Guerin.
PMID- 28412409
TI - Development of monoclonal antibodies against Sj29 and its possible application
for schistosomiasis diagnosis.
AB - OBJECTIVE: Timely Schistosoma japonicum detection improves outcomes in
schistosomiasis. Here, we established a double antibody sandwich ELISA to detect
Schistosoma japonicum. METHODS: Sj29 polyclonal and monoclonal antibodies were
developed and identified. A Sj29 double antibody sandwich ELISA was evaluated.
RESULTS: Assay sensitivity for detecting Schistosoma japonicum circulating
antigen Sj29 was 76.7% (23/30), 54.5% (18/33) and 50.0% (18/36) in patients with
acute, chronic and advanced schistosomiasis. No false positives or cross
reactivity was observed in healthy controls or patients with clonorchiasis,
paragonimiasis, or ancylostomiasis, respectively. By contrast, false positives
(5.7%) and cross-reactivity (6.5%-10%) were detected using an AWA-ELISA. The
circulating antigen positive rates decreased significantly faster than that of
the antibody detection after 6 months treatment (22.2%, 4/18 and 88.9%, 16/18).
Chi-Square Tests revealed that Sj29 sandwich ELISA had lower sensitivity than AWA
indirect ELISA in the detection of S. japonicum infected patients (p<0.05).
Although our assay detection specificity in patients infected with other
parasites or healthy controls appeared higher, the difference between the assays
was insignificant. However, our assay showed significantly better results in
monitoring praziquantel therapeutic effects (p=0.001), with antigen-positive
rates decreasing significantly faster than antibody detection rates after 6
months of treatment (22.2%, 4/18 versus 88.9%, 16/18). CONCLUSIONS: Sj29 double
antibody sandwich ELISA was established. The specificity of this method for
detecting healthy sera was 100%. Meanwhile, Sj29 sandwich ELISA may have a
potential diagnostic capability to distinguish current from past infections and
assess drug treatment responses.
PMID- 28412410
TI - Probable pulmonary Blastomyomycocis in an immunocompetent person.
AB - The current case report presents a 29-year old man who worked as a hotel guard in
a city in China. The patient had fever and dry cough before and after
hospitalization. Chest X-ray and CT revealed nodular and patchy lesions in both
lower lungs. There were no abnormal findings in the examination of sputum and
bronchoalveoular lavage fluid (BALF). He was diagnosed with pulmonary
blastomycosis by histological examination of lung biopsy and treated with
fluconazole. Follow-up chest CT examination demonstrated that the patient was
recovered through appropriate antifungal treatment.
PMID- 28412412
TI - Autophagy regulatory molecule, TMEM74, interacts with BIK and inhibits BIK
induced apoptosis.
AB - TMEM74 (Transmembrane protein 74), a lysosome transmembrane protein, induces cell
autophagy. Knockdown of TMEM74 abolished EBSS-induced autophagy. BIK, belonging
to BOP (BH3-only protein) protein family, has been reported to induce cell
apoptosis. Autophagy and apoptosis, as different pathways regulated by extra- or
intra-cellular signals precisely, both play a crucial role in processes of intra
cellular substrates degradation, energy metabolism and cell survival. However,
the relationship between autophagy and apoptosis still remains elusive. To
elucidate the putative new relationship and further identify the function of
TMEM74, we performed the study mainly using co-immunoprecipitation,
immunoblotting, fluorescent location and basic cell biologic experimental
techniques. In the present study, for the first time, it is demonstrated that
autophagy-related protein TMEM74 co-localizes with apoptosis-related protein BIK
in subcellular organelles. The data indicated that TMEM74 associates with BIK via
TM domains of TMEM74 and BH3 domain of BIK. Further investigations revealed that
TMEM74 inhibits BIK-induced apoptosis by interacting with BIK, as evidenced by
the results that autophagosome formation inhibitor could not block the inhibition
effect completely. On the contrary, knockdown of TMEM74 and the TM domain
deficient mutant led to deprivation of the function. Overall, the results
revealed the autophagy modulator TMEM74 interrelates with apoptosis inducer BIK
and inhibits its function, which provides a novel crosstalk point between
autophagy and apoptosis to enlarge our understanding of the programmed cell
death.
PMID- 28412411
TI - Mirtazapine and ketanserin alter preference for gambling-like schedules of
reinforcement in rats.
AB - Drug and behavioral addictions have overlapping features, e.g., both manifest
preference for larger, albeit costlier, reinforcement options in cost/benefit
decision-making tasks. Our prior work revealed that the mixed-function
serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by
abused drugs. To extend this work to behavioral addictions, here we determined if
mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound,
can alter decision-making in rats that is independent of drug (or food)-motivated
reward. Accordingly, we developed a novel variable-ratio task in rats wherein
intracranial self-stimulation was used as the positive reinforcer. Using lever
pressing for various levels of brain stimulation, the operant task provided
choices between a small brain stimulation current delivered on a fixed-ratio
schedule (i.e., a predictable reward) and a large brain stimulation delivered
following an unpredictable number of responses (i.e., a variable-ratio schedule).
This task allowed for demonstration of individualized preference and detection of
shifts in motivational influences during a pharmacological treatment. Once
baseline preference was established, we determined that pretreatment with
mirtazapine or ketanserin significantly decreased preference for the large
reinforcer presented after gambling-like schedules of reinforcement. When the
rats were tested the next day without drug, preference for the unpredictable
large reinforcer option was restored. These data demonstrate that mirtazapine and
ketanserin can reduce preference for larger, costlier reinforcement options, and
illustrate the potential for these drugs to alter behavior.
PMID- 28412413
TI - Activation of muscarinic receptors prevents TNF-alpha-mediated intestinal
epithelial barrier disruption through p38 MAPK.
AB - Intestinal epithelial cells form a tight barrier to act as selective physical
barriers, repelling hostile substances. Tumor necrosis factor-alpha (TNF-alpha)
is a well characterized pro-inflammatory cytokine which can compromise intestinal
barrier function and the suppression of TNF-alpha function is important for
treatment of inflammatory bowel disease (IBD). In this study, we investigated the
contribution of G-protein-coupled receptor (GPCR)-induced signalling pathways to
the maintenance of epithelial barrier function. We first demonstrated the
existence of functional muscarinic M3 and histamine H1 receptors in colonic
epithelial cell HT-29/B6. As we previously reported, muscarinic M3 receptor
prevented TNF-alpha-induced barrier disruption through acceleration of TNF
receptor (TNFR) shedding which is carried out by TNF-alpha converting enzyme
(TACE). M3 receptor-mediated suppression of TNF-alpha function depends on
Galphaq/11 protein, however, histamine H1 receptor could not ameliorate TNF-alpha
function, while which could induce Galphaq/11 dependent intracellular Ca2+
mobilization. We found that p38 MAPK was predominantly phosphorylated by M3
receptor through Galphaq/11 protein, whereas H1 receptor barely upregulated the
phosphorylation. Inhibition of p38 MAPK abolished M3 receptor-mediated TNFR
shedding and suppression of TNF-alpha-induced NF-kappaB signalling. The p38 MAPK
was also involved in TACE- mediated EGFR transactivation followed by ERK1/2
phosphorylation. These results indicate that not H1 but M3 receptor-induced
activation of p38 MAPK might contribute to the maintenance of epithelial barrier
function through down-regulation of TNF-alpha signalling and activation of EGFR.
PMID- 28412415
TI - Stress Echocardiography, Carotid Arteries, and More: Its Versatility for Our
Imaging Times.
PMID- 28412416
TI - Impaired Right Heart and Pulmonary Vascular Function in HFpEF: Time for More Risk
Markers?
PMID- 28412414
TI - Endothelin-1 promotes hypertrophic remodelling of cardiac myocytes by activating
sustained signalling and transcription downstream of endothelin type A receptors.
AB - G-protein coupled receptor (GPCR) mediated activation of the MAPK signalling
cascade is a key pathway in the induction of hypertrophic remodelling of the
heart - a response to pathological cues including hypertension and myocardial
infarction. While levels of pro-hypertrophic hormone agonists of GPCRs increase
during periods of greater workload to enhance cardiac output, hypertrophy does
not necessarily result. Here we investigated the relationship between the
duration of exposure to the pro-hypertrophic GPCR agonist endothelin-1 (ET-1) and
the induction of hypertrophic remodelling in neonatal rat ventricular myocytes
(NRVM) and in the adult rat heart in vivo. Notably, a 15min pulse of ET-1 was
sufficient to induce markers of hypertrophy that were present when measured at
24h in vivo and 48h in vitro. The persistence of ET-1 action was insensitive to
ET type A receptor (ETA receptor) antagonism with BQ123. The extended effects of
ET-1 were dependent upon sustained MAPK signalling and involved persistent
transcription. Inhibitors of endocytosis however conferred sensitivity upon the
hypertrophic response to BQ123, suggesting that endocytosis of ETA receptors
following ligand binding preserves their active state by protection against
antagonist. Contrastingly, alpha1 adrenergic-induced hypertrophic responses
required the continued presence of agonist and were sensitive to antagonist.
These studies shed new light on strategies to pharmacologically intervene in the
action of different pro-hypertrophic mediators.
PMID- 28412417
TI - Coronary Artery Disease Testing: Past, Present, and Future.
PMID- 28412418
TI - Pacemaker Implantation After TAVR.
PMID- 28412419
TI - Image Integration to Guide Wireless Endocardial LV Electrode Implantation for
CRT.
PMID- 28412420
TI - Stress Perfusion CMR in Patients With Known and Suspected CAD: Prognostic Value
and Optimal Ischemic Threshold for Revascularization.
AB - OBJECTIVES: This study sought to determine the ischemia threshold and additional
prognostic factors that identify patients for safe deferral from
revascularizations in a large cohort of all-comer patients with known or
suspected coronary artery disease (CAD). BACKGROUND: Stress-perfusion cardiac
magnetic resonance (CMR) is increasingly used in daily practice for ischemia
detection. However, there is insufficient evidence about the ischemia burden that
identifies patients who benefit from revascularization versus those with a good
prognosis who receive drugs only. METHODS: All patients with known or suspected
CAD referred to stress-perfusion CMR for myocardial ischemia assessment were
prospectively enrolled. The CMR examination included standard functional
adenosine stress first-pass perfusion (gadobutrol 0.1 mmol/kg Gadovist, Bayer AG,
Zurich, Switzerland) and late gadolinium enhancement (LGE) acquisitions. Presence
of ischemia and ischemia burden (number of ischemic segments on a 16-segment
model), and of scar and scar burden (number and transmurality of scar segments in
a 17-segment model) were assessed. The primary endpoint was a composite of
cardiac death, nonfatal myocardial infarction (MI), and late coronary
revascularization (>90 days post-CMR); the secondary endpoint was a composite of
cardiac death and nonfatal MI. RESULTS: During a follow-up of 2.5 +/- 1.0 years,
86 and 32 of 1,024 patients (1,103 screened patients) experienced the primary and
secondary endpoints, respectively. On Kaplan-Meier curves for the primary and
secondary endpoints, patients without ischemia had excellent outcomes that did
not differ from patients with <1.5 ischemic segments. In multivariate Cox
regression analyses of the entire population and of the subgroups, ischemia
burden (threshold: >=1.5 ischemic segments) was consistently the strongest
predictor of the primary and secondary endpoints with hazard ratios (HRs) of 7.42
to 8.72 (p < 0.001), whereas age (>=67 years), left ventricular ejection fraction
(<=40%), and scar burden (LGE score >=0.03) contributed significantly, but to a
lesser extent, in all models with HRs of 2.01 to 3.48, 1.75 to 1.96, and 1.66 to
1.76, respectively. CONCLUSIONS: In a large all-comer patient cohort with known
and suspected CAD, an ischemia burden of >=1.5 ischemic segments on stress
perfusion CMR was the strongest predictor of the primary and secondary endpoints.
Patients with zero or 1 ischemic segment can be safely deferred from
revascularizations.
PMID- 28412421
TI - Change in Carotid Plaque Components: A 4-Year Follow-Up Study With Serial MR
Imaging.
AB - OBJECTIVES: The goal of this study was to determine how carotid plaque components
(e.g., intraplaque hemorrhage [IPH], calcification, lipid core) change over time
and which cardiovascular risk factors are associated with the development of each
component. BACKGROUND: Carotid atherosclerotic plaque components are important
markers of plaque vulnerability. How these components change and which factors
lead to the development and changes in the components remain unclear. METHODS: A
total of 198 participants (mean age 67.5 +/- 10.6 years) from the population
based Rotterdam Study, all with carotid wall thickening on ultrasound, underwent
2 magnetic resonance imaging scans for carotid plaque characterization (mean
interscan interval 4.1 +/- 0.2 years). Presence of IPH, calcification, and lipid
rich necrotic core was assessed on both sides on the baseline and follow-up
scans. The association between cardiovascular risk factors and incident carotid
plaque components was assessed. RESULTS: In the 396 arteries, all plaque
components significantly changed over time. Incidence of IPH, calcification, and
lipid core was, respectively, 18.5%, 59.2%, and 39.6%. The factor most strongly
associated with the incidence of IPH was use of antihypertensive drugs
(multivariate adjusted odds ratio [OR]: 3.87; 95% confidence interval [CI]: 1.90
to 7.90) and severe hypertension (multivariate adjusted OR: 4.70; 95% CI: 1.50 to
14.80). The incidence of calcification was associated with hypertension (OR:
2.20; 95% CI: 1.07 to 4.40). Higher cholesterol levels were associated with
incidence of lipid cores (multivariate adjusted OR per unit increase in
cholesterol: 1.40; 95% CI: 1.10 to 1.70). CONCLUSIONS: In these community
dwelling subjects, characteristics of plaque composition changed dramatically
within a few years, and cardiovascular risk factors played a major role in these
changes. Hypertension and its treatment and serum cholesterol levels were the
main risk factors for the development of atherosclerotic plaque components over
time.
PMID- 28412422
TI - Risk Factors for Development of Carotid Plaque Components.
PMID- 28412424
TI - Toward Noninvasive Assessment of CVP Variations Using Real-Time and Quantitative
Liver Stiffness Estimation.
PMID- 28412423
TI - RV Contractile Function and its Coupling to Pulmonary Circulation in Heart
Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes
and Outcomes.
AB - OBJECTIVES: This study sought to investigate how right ventricular (RV)
contractile function and its coupling with pulmonary circulation (PC) stratify
clinical phenotypes and outcome in heart failure preserved ejection fraction
(HFpEF) patients. BACKGROUND: Pulmonary hypertension and RV dysfunction are key
hemodynamic abnormalities in HFpEF. METHODS: Three hundred eighty seven HFpEF
patients (mean age 64 +/- 12 years, 59% females, left ventricular ejection
fraction 59 +/- 7%) underwent RV and pulmonary hemodynamic evaluation by
echocardiography (entire population) and right heart catheterization (219
patients). Patients were investigated by tricuspid annular plane systolic
excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and
stratified according to TAPSE/PASP ratio tertiles (1: <0.35; 2: 0.35 to 0.57; 3:
>0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to
PC coupling based on the correlation with invasively evaluated RV systolic
elastance/arterial elastance (r = 0.35; p < 0.0001). RESULTS: Groups had similar
prevalence of comorbidities except for a higher prevalence of atrial fibrillation
and kidney dysfunction in tertile 1. Progressively increasing levels of
natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal
exercise aerobic capacity and ventilatory inefficiency were observed from the
highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery
compliance (r = 0.69; p < 0.0001). Remarkably, the tertile 1 group distributed
along the worse portion of the curve at lower pulmonary artery compliance and
higher pulmonary vascular resistances. In addition, the TAPSE/PASP ratio emerged
as an independent predictor of worse outcomes. CONCLUSIONS: A thorough assessment
of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at
different level of risk. These observations shift the interest toward therapeutic
strategies that may benefit the right heart as primary unmet need in the complex
pathophysiology of the HFpEF syndrome.
PMID- 28412425
TI - Aortic Dilatation in Repaired Tetralogy of Fallot.
PMID- 28412426
TI - Unraveling the RV Ejection Doppler Envelope: Insight Into Pulmonary Artery
Hemodynamics and Disease Severity.
AB - OBJECTIVES: The purpose of this study was to characterize the profiles of right
ventricular outflow tract (RVOT) Doppler flow velocity envelopes in patients with
pulmonary arterial hypertension (PAH) and to establish whether changes in the
RVOT flow profile related to patient outcome. BACKGROUND: The RVOT systolic flow
profile is frequently abnormal, with findings of a mid-systolic flow deceleration
and notching, previously proposed as an indicator of elevated pulmonary vascular
resistance (PVR). METHODS: We reviewed RVOT systolic flow profiles recorded by
pulsed-wave Doppler from 159 consecutive patients with PAH and measured
deceleration time (DT) of mid-systolic deceleration slope (mid-systolic DT) and
the peak velocity of pre- and post-notching flow. Concurrent right-heart
catheterization was available in all (41 of 41) incident patients and in 39 of
118 established patients. Outcomes, defined as time to all-cause mortality or
need for lung transplantation, were assessed during 3 years of follow-up.
RESULTS: Notched envelopes were identified in 150 of 159 patients. The presence
of a notched pattern and a decrease in the mid-systolic DT were associated with
higher PA pressures; higher PVR; and, at a threshold of a mid-systolic DT of <120
ms, worse outcome. Those patients with a shorter DT were further subdivided based
on the post-notch systolic flow velocity. In these patients, a decline in the
post-notch flow velocity to <62% of the pre-notch flow velocity defined a cohort
with a marked reduction in systolic function and the worst outcome. CONCLUSIONS:
In PAH, the notched profile of RVOT Doppler flow velocity envelope appears to
integrate indicators of pulmonary vascular load and RV function and serves as a
marker for adverse outcomes.
PMID- 28412427
TI - CMR-Verified Regression of Cardiac AL Amyloid After Chemotherapy.
PMID- 28412428
TI - Increased Iron Deposition Is Directly Associated With Myocardial Dysfunction in
Patients With Sickle Cell Disease.
PMID- 28412429
TI - Myocardial Inflammation: An Important Pitfall During CMR T1 Mapping for the
Quantification of Diffuse Fibrosis in Heart Failure.
PMID- 28412430
TI - Incremental Prognostic Value of Stress Echocardiography With Carotid Ultrasound
for Suspected CAD.
AB - OBJECTIVES: This study hypothesized that ischemia and atherosclerosis assessment
by ultrasound (US) may provide incremental prognostic information in patients
with new-onset chest pain who do not have coronary artery disease (CAD).
BACKGROUND: The clinical significance of atherosclerosis assessment by carotid US
in patients undergoing stress echocardiography (SE) in such patients is unknown.
METHODS: Consecutive patients with suspected angina but no history of CAD
underwent simultaneous SE and US prospectively to assess myocardial ischemia and
carotid plaque burden (CPB), respectively. Patients were followed up for major
adverse events (MAEs)-all-cause mortality, nonfatal myocardial infarction, and
unplanned coronary revascularization. RESULTS: Of 591 recruited patients, 580
(men, 46%; mean age 59 +/- 11 years) patients were available for follow-up. SE
demonstrated myocardial ischemia in 12%, but prevalence of carotid plaques was
59%. During a mean follow-up of 1,117 +/- 361 days, 40 first MAEs occurred. In
the multivariable regression model, pre-test probability (PTP) of CAD (p =
0.001), abnormal SE (p < 0.0001), and CPB (p < 0.0001) predicted MAEs. MAE rates
per year increased from 0.9% versus 1.97% versus 4.3% versus 9.7% in patients
with no carotid plaque and normal SE versus patients who had plaque and normal SE
versus those with no plaque and abnormal SE versus patients with plaque and
abnormal SE, respectively (p < 0.0001). In hierarchical analysis, plaque burden
provided incremental prognostic value over PTP of CAD and SE; likewise, SE was
incremental to PTP-CAD and CPB (p < 0.0001 for both). CONCLUSIONS: In patients
with suspected stable angina without known CAD, simultaneous SE (for ischemia)
and US (for atherosclerosis) provided incremental prognostic value.
PMID- 28412431
TI - 3D Morphological Changes in LV and RV During LVAD Ramp Studies.
AB - OBJECTIVES: The purpose of this study was to investigate the differential impact
of the 2 most commonly available left ventricular assist device (LVAD) types on
the right ventricle (RV) and left ventricle (LV) using 3-dimensional (3D)
echocardiography-based analysis of ventricular morphology. BACKGROUND: LVADs have
emerged as common therapy for advanced heart failure. Recent data suggest that
the heart responds differently to speed settings in the 2 main devices available
(HeartMate II [HMII], St Jude Medical, Pleasanton, California, and HVAD,
HeartWare International, Framingham, Massachusetts). The authors hypothesized
that 3D echocardiographic assessment of LV and RV volumes and shape would help
describe the differential impact of the 2 LVAD types on the heart. METHODS:
Simultaneous 3D echocardiography, ramp test, and right heart catheterization were
performed in 31 patients with LVADs (19 with HMII and 12 with HVAD). Device speed
was increased stepwise (8,000 to 12,000 for HMII and 2,300 to 3,200 revolutions
per minute for HVAD). 3D echocardiographic full-volume LV and RV datasets were
acquired, and endocardial surfaces were analyzed using custom software to
calculate LV sphericity, conicity (perfect sphere/cone = 1) and RV septal and
free-wall curvature (0 = flat; <0 = concave; >0 = convex). RESULTS: For both
devices, cardiac output increased and wedge pressure decreased with increasing
speed. In HMII, LV volumes progressively decreased (meanDelta = 127 ml) as the LV
became less spherical and more conical, whereas the RV volume initially remained
stable, but subsequently increased at higher speeds (meanDelta = 60 ml). Findings
for the HVAD were similar, but less pronounced (LV:meanDelta = 51 ml,
RV:meanDelta = 22 ml), and the LV remained significantly more spherical even at
high speeds. On average, in HMII patients, the RV septum became more convex
(bulging into the LV) at the highest speeds whereas in HVAD patients, there was
no discernable change in the RV septum. CONCLUSIONS: The heart responds
differently to pump speed changes with the 2 types of LVAD, as reflected by the
volume and shape changes of both the LV and RV. Our study suggests that adding RV
assessment to the clinical echo-ramp study may better optimize LVAD speed.
Further study is needed to determine whether this would have an impact on patient
outcomes.
PMID- 28412432
TI - Prognostic Value and Determinants of CMR-Derived Left Atrial Function Assessed in
STEMI.
PMID- 28412433
TI - Increased Lipid Length, Macrophage Infiltration, and Neovascularization in
Coronary Atheroma From Patients With Chronic Kidney Disease.
PMID- 28412434
TI - A Highly Predictive Risk Model for Pacemaker Implantation After TAVR.
AB - OBJECTIVES: This study sought to develop a robust and definitive risk model for
new permanent pacemaker implantation (PPMI) after SAPIEN 3 (third generation
balloon expandable valve) (Edwards Lifesciences, Irvine, California)
transcatheter aortic valve replacement (third generation balloon expandable valve
TAVR), including calcification in the aortic-valvular complex (AVC). BACKGROUND:
The association between calcium in the AVC and need for PPMI is poorly delineated
after third generation balloon expandable valve TAVR. METHODS: At Cedars-Sinai
Heart Institute in Los Angeles, California, a total of 240 patients with severe
aortic stenosis underwent third generation balloon expandable valve TAVR and had
contrast computed tomography. AVC was characterized precisely by leaflet sector
and region. RESULTS: The total new PPMI rate was 14.6%. On multivariate analysis
for predictors of PPMI, pre-procedure third generation balloon expandable valve
TAVR, right bundle branch block (RBBB), shorter membranous septum (MS) length,
and noncoronary cusp device-landing zone calcium volume (NCC-DLZ CA) were
included. Predictive probabilities were generated using this logistic regression
model. If 3 pre-procedural risk factors were present, the c-statistic of the
model for PPMI was area under the curve of 0.88, sensitivity of 77.1%, and
specificity of 87.1%; this risk model had high negative predictive value (95.7%).
The addition of the procedural factor of device depth to the model, with the
parameter of difference between implantation depth and MS length, combined with
RBBB and NCC-DLZ CA increased the c-statistic to 0.92, sensitivity to 94.3%,
specificity to 83.8%, and negative predictive value to 98.8% CONCLUSIONS: By
using a precise characterization of distribution of calcification in the AVC in a
single-center, retrospective study, NCC-DLZ CA was found to be an independent
predictor of new PPMI post-third generation balloon expandable valve TAVR. The
findings also reinforce the importance of short MS length, pre-existing RBBB, and
ventricular implantation depth as important synergistic PPMI risk factors. This
risk model will need validation by future prospective multicenter studies.
PMID- 28412435
TI - CMR-Derived Extracellular Volume Fraction as a Marker for Myocardial Fibrosis:
The Importance of Coexisting Myocardial Inflammation.
AB - OBJECTIVES: The aim of the present study was to evaluate whether extracellular
volume fraction (ECV) can reliably inform on the extent of diffuse fibrosis in
the simultaneous presence of myocardial inflammation, which has not been verified
to date. BACKGROUND: Diffuse myocardial fibrosis is associated with unfavorable
outcome in patients with cardiomyopathy, and is of prognostic relevance.
Assessment of ECV bears promise for being a noninvasive surrogate parameter, but
it may be altered by other pathologies. METHODS: In this prospective study, 107
consecutive patients with clinical suspicion of inflammatory cardiomyopathy were
included. All patients underwent left ventricular (LV) endomyocardial biopsy
(EMB) and cardiac magnetic resonance imaging on a 1.5-T scanner. T1 mapping was
obtained with the modified Look-Locker inversion recovery sequence, and ECV was
calculated. RESULTS: Myocardial inflammation was present in 66 patients. Patients
with and without inflammation were of similar age and had comparable LV ejection
fraction (37 +/- 17% vs. 36 +/- 18%; p = 0.9) and symptom duration (median 14
days [interquartile range: 5 to 36 days] vs. median 14 days [interquartile range:
7 to 30 days]; p = 0.73). Although LV collagen volume percentage was comparable
between groups (inflammation 12.3 +/- 17.8% vs. noninflammation 11.4 +/- 7.9%; p
= 0.577), ECV was significantly higher in patients with inflammation (0.37 +/-
0.06%) than in those without inflammation (0.33 +/- 0.08%; p = 0.02).
Importantly, ECV adequately estimated the degree of LV fibrosis percentage only
in patients without inflammation (r = 0.72; p < 0.0001) and not in those with
inflammation (r = 0.24; p = 0.06). CONCLUSIONS: These findings prove the
theoretical concept of ECV as an estimate for diffuse myocardial fibrosis, but
only in the absence of significant myocardial inflammation. Assuming that various
degrees of myocardial inflammation and fibrosis coexist in such a scenario, the
measured ECV will reflect a sum of these different pathologies but will not
inform solely on the extent of diffuse fibrosis.
PMID- 28412437
TI - 3D Echocardiography and Ventricular Unloading With Continuous Flow LVAD:
Potential Advantages to Optimize Patient Outcome.
PMID- 28412436
TI - Noninvasive FFR Derived From Coronary CT Angiography: Management and Outcomes in
the PROMISE Trial.
AB - OBJECTIVES: The purpose of this study was to determine whether noninvasive
fractional flow reserve derived from computed tomography (FFRCT) predicts
coronary revascularization and outcomes and whether its addition improves
efficiency of referral to invasive coronary angiography (ICA) after coronary
computed tomography angiography (CTA). BACKGROUND: FFRCT may improve the
efficiency of an anatomic CTA strategy for stable chest pain. METHODS: This
observational cohort study included patients with stable chest pain in the
PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain)
trial referred to ICA within 90 days after CTA. FFRCT was measured at a blinded
core laboratory, and FFRCT results were unavailable to caregivers. We determined
the agreement of FFRCT (positive if <=0.80) with stenosis on CTA and ICA
(positive if >=50% left main or >=70% other coronary artery), and predictive
value for a composite of coronary revascularization or major adverse cardiac
events (death, myocardial infarction, or unstable angina). We retrospectively
assessed whether adding FFRCT <=0.80 as a gatekeeper could improve efficiency of
referral to ICA, defined as decreased rate of ICA without >=50% stenosis and
increased ICA leading to revascularization. RESULTS: FFRCT was calculated in 67%
(181 of 271) of eligible patients (mean age 62 years; 36% women). FFRCT was
discordant with stenosis in 31% (57 of 181) for CTA and 29% (52 of 181) for ICA.
Most patients undergoing coronary revascularization had an FFRCT of <=0.80 (91%;
80 of 88). An FFRCT of <=0.80 was a significantly better predictor for
revascularization or major adverse cardiac events than severe CTA stenosis (HR:
4.3 [95% confidence interval [CI]: 2.4 to 8.9] vs. 2.9 [95% CI: 1.8 to 5.1]; p =
0.033). Reserving ICA for patients with an FFRCT of <=0.80 could decrease ICA
without >=50% stenosis by 44%, and increase the proportion of ICA leading to
revascularization by 24%. CONCLUSIONS: In this hypothesis-generating study of
patients with stable chest pain referred to ICA from CTA, an FFRCT of <=0.80 was
a better predictor of revascularization or major adverse cardiac events than
severe stenosis on CTA. Adding FFRCT may improve efficiency of referral to ICA
from CTA alone.
PMID- 28412438
TI - Torsional stress promotes trinucleotidic expansion in spermatids.
AB - Trinucleotide repeats are involved in various neurodegenerative diseases and are
highly unstable both in dividing or non-dividing cells. In Huntington disease
(HD), the age of onset of symptoms is inversely correlated to the number of CAG
repeats within exon 1 of the HTT gene. HD shows paternal anticipation as CAG
repeats are increased during spermatogenesis. CAG expansion were indeed found to
be generated during the chromatin remodeling in spermatids where most histones
are evicted and replaced by protamines. This process involves striking change in
DNA topology since free supercoils must be eliminated. Using an in vitro CAG
repeat reporter assay and a highly active nuclear extracts from spermatids, we
demonstrate that free negative supercoils result in CAG TNR expansion at a
stabilized hairpin. We also suggest a possible role for protamines in promoting
localized torsional stress and consequently TNR expansion. The transient increase
in torsional stress during spermiogenesis may therefore provide an ideal context
for the generation of such secondary DNA structures leading to the paternal
anticipation of trinucleotidic diseases.
PMID- 28412439
TI - Musical literacy shifts asymmetries in the ventral visual cortex.
AB - The acquisition of literacy has a profound impact on the functional
specialization and lateralization of the visual cortex. Due to the overall
lateralization of the language network, specialization for printed words develops
in the left occipitotemporal cortex, allegedly inducing a secondary shift of
visual face processing to the right, in literate as compared to illiterate
subjects. Applying the same logic to the acquisition of high-level musical
literacy, we predicted that, in musicians as compared to non-musicians,
occipitotemporal activations should show a leftward shift for music reading, and
an additional rightward push for face perception. To test these predictions,
professional musicians and non-musicians viewed pictures of musical notation,
faces, words, tools and houses in the MRI, and laterality was assessed in the
ventral stream combining ROI and voxel-based approaches. The results supported
both predictions, and allowed to locate the leftward shift to the inferior
temporal gyrus and the rightward shift to the fusiform cortex. Moreover, these
laterality shifts generalized to categories other than music and faces. Finally,
correlation measures across subjects did not support a causal link between the
leftward and rightward shifts. Thus the acquisition of an additional perceptual
expertise extensively modifies the laterality pattern in the visual system.
PMID- 28412440
TI - Transient networks of spatio-temporal connectivity map communication pathways in
brain functional systems.
AB - The study of brain dynamics enables us to characterize the time-varying
functional connectivity among distinct neural groups. However, current methods
suffer from the absence of structural connectivity information. We propose to
integrate infra-slow neural oscillations and anatomical-connectivity maps, as
derived from functional and diffusion MRI, in a multilayer-graph framework that
captures transient networks of spatio-temporal connectivity. These networks group
anatomically wired and temporary synchronized brain regions and encode the
propagation of functional activity on the structural connectome. In a group of 71
healthy subjects, we find that these transient networks demonstrate power-law
spatial and temporal size, globally organize into well-known functional systems
and describe wave-like trajectories of activation across anatomically connected
regions. Within the transient networks, activity propagates through polysynaptic
paths that include selective ensembles of structural connections and differ from
the structural shortest paths. In the light of the communication-through
coherence principle, the identified spatio-temporal networks could encode
communication channels' selection and neural assemblies, which deserves further
attention. This work contributes to the understanding of brain structure-function
relationships by considering the time-varying nature of resting-state
interactions on the axonal scaffold, and it offers a convenient framework to
study large-scale communication mechanisms and functional dynamics.
PMID- 28412441
TI - Noise-robust cortical tracking of attended speech in real-world acoustic scenes.
AB - Selectively attending to one speaker in a multi-speaker scenario is thought to
synchronize low-frequency cortical activity to the attended speech signal. In
recent studies, reconstruction of speech from single-trial electroencephalogram
(EEG) data has been used to decode which talker a listener is attending to in a
two-talker situation. It is currently unclear how this generalizes to more
complex sound environments. Behaviorally, speech perception is robust to the
acoustic distortions that listeners typically encounter in everyday life, but it
is unknown whether this is mirrored by a noise-robust neural tracking of attended
speech. Here we used advanced acoustic simulations to recreate real-world
acoustic scenes in the laboratory. In virtual acoustic realities with varying
amounts of reverberation and number of interfering talkers, listeners selectively
attended to the speech stream of a particular talker. Across the different
listening environments, we found that the attended talker could be accurately
decoded from single-trial EEG data irrespective of the different distortions in
the acoustic input. For highly reverberant environments, speech envelopes
reconstructed from neural responses to the distorted stimuli resembled the
original clean signal more than the distorted input. With reverberant speech, we
observed a late cortical response to the attended speech stream that encoded
temporal modulations in the speech signal without its reverberant distortion.
Single-trial attention decoding accuracies based on 40-50s long blocks of data
from 64 scalp electrodes were equally high (80-90% correct) in all considered
listening environments and remained statistically significant using down to 10
scalp electrodes and short (<30-s) unaveraged EEG segments. In contrast to the
robust decoding of the attended talker we found that decoding of the unattended
talker deteriorated with the acoustic distortions. These results suggest that
cortical activity tracks an attended speech signal in a way that is invariant to
acoustic distortions encountered in real-life sound environments. Noise-robust
attention decoding additionally suggests a potential utility of stimulus
reconstruction techniques in attention-controlled brain-computer interfaces.
PMID- 28412442
TI - Human brain mapping: A systematic comparison of parcellation methods for the
human cerebral cortex.
AB - The macro-connectome elucidates the pathways through which brain regions are
structurally connected or functionally coupled to perform a specific cognitive
task. It embodies the notion of representing and understanding all connections
within the brain as a network, while the subdivision of the brain into
interacting functional units is inherent in its architecture. As a result, the
definition of network nodes is one of the most critical steps in connectivity
network analysis. Although brain atlases obtained from cytoarchitecture or
anatomy have long been used for this task, connectivity-driven methods have
arisen only recently, aiming to delineate more homogeneous and functionally
coherent regions. This study provides a systematic comparison between anatomical,
connectivity-driven and random parcellation methods proposed in the thriving
field of brain parcellation. Using resting-state functional MRI data from the
Human Connectome Project and a plethora of quantitative evaluation techniques
investigated in the literature, we evaluate 10 subject-level and 24 groupwise
parcellation methods at different resolutions. We assess the accuracy of
parcellations from four different aspects: (1) reproducibility across different
acquisitions and groups, (2) fidelity to the underlying connectivity data, (3)
agreement with fMRI task activation, myelin maps, and cytoarchitectural areas,
and (4) network analysis. This extensive evaluation of different parcellations
generated at the subject and group level highlights the strengths and
shortcomings of the various methods and aims to provide a guideline for the
choice of parcellation technique and resolution according to the task at hand.
The results obtained in this study suggest that there is no optimal method able
to address all the challenges faced in this endeavour simultaneously.
PMID- 28412443
TI - Separating blood and water: Perfusion and free water elimination from diffusion
MRI in the human brain.
AB - The assessment of the free water fraction in the brain provides important
information about extracellular processes such as atrophy and neuroinflammation
in various clinical conditions as well as in normal development and aging. Free
water estimates from diffusion MRI are assumed to account for freely diffusing
water molecules in the extracellular space, but may be biased by other pools of
molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM)
of blood, where water molecules perfuse in the randomly oriented capillary
network. The goal of this work was to separate the signal contribution of the
perfusing blood from that of free-water and of other brain diffusivities. The
influence of the vascular compartment on the estimation of the free water
fraction and other diffusivities was investigated by simulating perfusion in
diffusion MRI data. The perfusion effect in the simulations was significant,
especially for the estimation of the free water fraction, and was maintained as
long as low b-value data were included in the analysis. Two approaches to reduce
the perfusion effect were explored in this study: (i) increasing the minimal b
value used in the fitting, and (ii) using a three-compartment model that
explicitly accounts for water molecules in the capillary blood. Estimation of the
model parameters while excluding low b-values reduced the perfusion effect but
was highly sensitive to noise. The three-compartment model fit was more stable
and additionally, provided an estimation of the volume fraction of the capillary
blood compartment. The three-compartment model thus disentangles the effects of
free water diffusion and perfusion, which is of major clinical importance since
changes in these components in the brain may indicate different pathologies,
i.e., those originating from the extracellular space, such as neuroinflammation
and atrophy, and those related to the vascular space, such as vasodilation,
vasoconstriction and capillary density. Diffusion MRI data acquired from a
healthy volunteer, using multiple b-shells, demonstrated an expected non-zero
contribution from the blood fraction, and indicated that not accounting for the
perfusion effect may explain the overestimation of the free water fraction
evinced in previous studies. Finally, the applicability of the method was
demonstrated with a dataset acquired using a clinically feasible protocol with
shorter acquisition time and fewer b-shells.
PMID- 28412444
TI - Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1:
Implications for preeclampsia development.
AB - Preeclampsia (PE) is a major contributor to maternal morbidity and mortality.
However, the molecular mechanisms underlying PE progression are not well
characterized. Here, we investigated the role of miR-218 in PE development. The
expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in
preeclamptic placentae compared to normal placentae. miR-218 expression was
induced by hypoxia and decreased after knockdown of HIF-1alpha in an extravillous
trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed
direct binding of HIF-1alpha to the promoters of SLIT2 and SLIT3. Bioinformatics
analysis identified LASP1 as a direct target of miR-218. Overexpression of miR
218 repressed the expression of LASP1 at both the mRNA and protein level.
Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the
3'-untranslated region of the LASP1 gene. Furthermore, expression of LASP1
rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together,
these results indicated that miR-218 contributes to PE by targeting LASP1 to
inhibit trophoblast invasion.
PMID- 28412445
TI - Methylphenidate effects in the young brain: friend or foe?
AB - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent
neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH)
is a first-line stimulant drug available worldwide for its treatment. Despite the
proven therapeutic efficacy, concerns have been raised regarding the possible
consequences of chronic MPH exposure during childhood and adolescence.
Disturbances in the neurodevelopment at these crucial stages are major concerns
given the unknown future life consequences. This review is focused on the long
term adverse effects of MPH to the brain biochemistry. Reports conducted with
young and/or adolescent animals and studies with humans are reviewed in the
context of long-term consequences after early life-exposure. MPH pharmacokinetics
is also reviewed as there are differences among laboratory animals and humans
that may be relevant to extrapolate the findings. Studies reveal that exposure to
MPH in laboratory animals during young and/or adolescent ages can impact the
brain, but the outcomes are dependent on MPH dose, treatment period, and animal's
age. Importantly, the female sex is largely overlooked in both animal and human
studies. Unfortunately, human reports that evaluate adults following adolescent
or child exposure to MPH are very scarce. In general, human data indicates that
MPH is generally safe, although it can promote several brain changes in early
ages. Even so, there is a lack of long course patient evaluation to clearly
establish whether MPH-induced changes are friendly or foe to the brain and more
human studies are needed to assess the adult brain changes that arise from early
MPH treatment.
PMID- 28412447
TI - Improved release of triamcinolone acetonide from medicated soft contact lenses
loaded with drug nanosuspensions.
AB - Drug nanosuspensions (NSs) show a significant potential to improve loading and
release properties of the poorly water soluble drug triamcinolone acetonide (TA)
from poly(hydroxyethyl methacrylate) (pHEMA) soft contact lenses. In this work,
TA NSs were developed by a controlled precipitation method using a fractional
factorial Plackett-Burmann design. Poloxamer 407 (PL) and polyvinyl alcohol (PVA)
as stabilizing agents were selected. NSs were characterized in terms of their
drug content, particle size and morphology. Results indicate that all studied
factors, except homogenization speed and sonication, have significant influence
on the drug incorporation yield into NSs. Drug nanoparticles showed an
interesting size that may be suitable for their incorporation into topical ocular
drug delivery systems, as hydrogels. pHEMA hydrogels and daily-wear Hilafilcon B
commercial contact lenses (SCLs) were employed to study TA loading capacity and
drug release properties using NSs as loading system. Hydrogels have been
synthesised by copolymerization of 2-hydroxyethyl methacrylate (HEMA) with
methacrylic acid (MA) in accordance with a previous work (Garcia-Millan et al.,
2015). Both synthesised hydrogels and SCLs were characterized in terms of their
mechanical and physical properties and TA loading and release properties.
Selected TA NS was further characterized by studying its physical-chemical
stability during the loading process. Results show that the use of TA NSs as
loading medium significantly increases drug loading capacity and release of soft
contact lenses in comparison with drug saturated solution. Synthesised pHEMA
hydrogels and SCLs lenses have good properties as ophthalmic drug delivery
systems, but SCLs load higher quantities of drug and release TA in shorter time
periods than synthesised pHEMA hydrogel.
PMID- 28412446
TI - Development and characterization of mucoadhesive buccal gels containing lipid
nanoparticles of ibuprofen.
AB - The lipid nanoparticles, namely Nanostructured Lipid Carriers (NLC), as drug
delivery systems have been investigated for several years. One of the delivery
routes for which these carriers can be applied is buccal administration. However,
the liquid dispersions of lipid nanoparticles can be rapidly removed from oral
cavity by saliva. Thus, the development of a system that allows increased
retention time on the mucosa is necessary. For this reason, the development of
mucoadhesive preparations for buccal administration of lipid nanoparticles
becomes important. Hydrogels prepared with mucoadhesive polymers (Carbopol(r) 980
and polycarbophil) constitute a promising option. The aim of this work was to
develop mucoadhesive buccal hydrogels with NLC, using ibuprofen as a model drug.
The obtained results showed that the developed NLC dispersions presented
particles in the nanometric size range, with low polydispersity index values and
efficient ability for the entrapment of the model drug. Moreover, the
incorporation of NLC in hydrogels of mucoadhesive polymers resulted in
preparations with desirable rheological features as well as texture (firmness and
adhesiveness) and mucoadhesive properties, which could benefit the therapeutic
efficacy, by increasing the residence time and easiness for topical application
in the buccal mucosa. Additionally, the developed preparations exhibited
sustained drug release as intended for these systems.
PMID- 28412448
TI - Self-assembled liposomes of dual paclitaxel-phospholipid prodrug for anticancer
therapy.
AB - In this report, a newly liposomal formulation of paclitaxel (PTX) based on dual
paclitaxel succinate glycerophosphorylcholine (Di-PTX-GPC) prodrug was developed.
The Di-PTX-GPC prodrug was synthesized by conjugating PTX with GPC through
esterification under N,N'-carbonyldiimidazole (CDI) and 1,8
diazabicyclo[5.4.0]undec-7-ene (DBU) catalytic system. Di-PTX-GPC liposomes were
prepared by thin film method and characterized by dynamic light scattering (DLS)
and transmission electron microscope (TEM). The results indicated that the
liposomes have an average diameter of 157.9nm with well-defined spherical
morphology. In vitro drug release studies confirmed that the Di-PTX-GPC liposomes
have controlled release profile of PTX at a weakly acidic environment, which
formulates them suitable for sustained drug delivery. Additionally, in vitro
cellular uptake analysis and cytotoxicity evaluation showed that Di-PTX-GPC
liposomes were internalized successfully into tumor cells to induce the apoptosis
against MCF-7, HeLa and HepG-2 cells. In vivo pharmacokinetics study revealed
that such liposomal formulation of Di-PTX-GPC has longer retention half-life in
bloodstream, which subsequently leads to slight accumulate in tumor sites due to
enhanced permeability and retention (EPR) effect. More importantly, Di-PTX-GPC
liposomes demonstrated good in vivo anticancer activities compared to Taxol with
reduced adverse effects. Conclusively, these results suggest that Di-PTX-GPC
liposomes could be an effective PTX delivery vehicles in clinical cancer
chemotherapy.
PMID- 28412449
TI - Targeted drug delivery system to neural cells utilizes the nicotinic
acetylcholine receptor.
AB - Drug delivery to the brain is still a major challenge in the field of
therapeutics, especially for large and hydrophilic compounds. In order to achieve
drug delivery of therapeutic concentration in the central nervous system, the
problematic blood brain barrier (BBB) must be overcome. This work presents the
formulation of a targeted nanoparticle-based drug delivery system using a
specific neural cell targeting ligand, rabies virus derived peptide (RDP).
Characterization studies revealed that RDP could be conjugated to drug-loaded
PLGA nanoparticles of average diameter 257.10+/-22.39nm and zeta potential of
5.51+/-0.73mV. In vitro studies showed that addition of RDP to nanoparticles
enhanced drug accumulation in a neural cell line specifically as opposed to non
neural cell lines. It was revealed that this drug delivery system is reliant upon
nicotinic acetylcholine receptor (nAChR) function for RDP-facilitated effects,
supporting a cellular uptake mechanism of action. The specific neural cell
targeting capabilities of RDP via the nAChR offers a non-toxic, non-invasive and
promising approach to the delivery of therapeutics to the brain.
PMID- 28412450
TI - PEGylated doxorubicin nanoparticles mediated by HN-1 peptide for targeted
treatment of oral squamous cell carcinoma.
AB - HN-1, a 12-amino acid peptide, has been reported to possess strong capabilities
for targeting and penetrating head and neck squamous cell carcinoma. Here, we
designed a simple but effective nanoparticle system for the delivery of
doxorubicin (DOX) targeting oral squamous cell carcinoma (OSCC) through the
mediation of HN-1. PEGylated DOX (PD) was firstly synthesized by the conjugation
of DOX with bis-amino-terminated poly(ethylene glycol) via succinyl linkage, and
then PD nanoparticles were prepared by a modified nanoprecipitation method. After
that, PD nanoparticles were surface-modified with HN-1 to form HNPD
nanoparticles, which had a uniform spherical shape and a small size about 150nm.
In human OSCC cells (CAL-27 and SCC-25), HNPD nanoparticles exhibited
significantly higher cellular uptakes and cytotoxicities than PD nanoparticles.
Furthermore, HNPD nanoparticles showed a certain degree of functional selectivity
for CAL-27 and SCC-25 cells as compared to human hepatoma HepG2 cells. In SCC-25
tumor-bearing nude mice, HNPD nanoparticles showed remarkably enhanced tumor
targeting and penetrating efficiencies as compared to PD nanoparticles, and
effectively inhibited the tumor growth. In conclusion, our study demonstrated for
the first time that HN-1 could be used for mediating the OSCC-targeted delivery
of nanoparticles.
PMID- 28412451
TI - Laser-treated electrospun fibers loaded with nano-hydroxyapatite for bone tissue
engineering.
AB - Core-shell polycaprolactone/polycaprolactone (PCL/PCL) and
polycaprolactone/polyvinyl acetate (PCL/PVAc) electrospun fibers loaded with
synthesized nanohydroxyapatite (HAn) were lased treated to create microporosity.
The prepared materials were characterized by XRD, FTIR, TEM and SEM. Uniform and
randomly oriented beadless fibrous structures were obtained in all cases. Fibers
diameters were in the 150-300nm range. Needle-like HAn nanoparticles with mean
diameters of 20nm and length of approximately 150nm were mostly encase inside the
fibers. Laser treated materials present micropores with diameters in the range 70
120MUm for PCL-HAn/PCL fibers and in the 50-90MUm range for PCL-HAn/PVAC
material. Only samples containing HAn presented bioactivity after incubation
during 30days in simulated body fluid. All scaffolds presented high viability,
very low mortality, and human osteoblast proliferation. Biocompatibility was
increased by laser treatment due to the surface and porosity modification.
PMID- 28412452
TI - Enhancement of dissolution rate through eutectic mixture and solid solution of
posaconazole and benznidazole.
AB - Benznidazole (BNZ), the only commercialized antichagasic drug, and the antifungal
compound posaconazole (PCZ) have shown synergistic action in the therapy of
Chagas disease, however both active pharmaceutical ingredients (APIs) exhibit low
aqueous solubility potentially limiting their bioavailability and therapeutic
efficacy. In this paper, we report for the first time the formation of a eutectic
mixture as well as an amorphous solid solution of PCZ and BNZ (at the same
characteristic ratio of 80:20wt%), which provided enhanced solubility and
dissolution rate for both APIs. This eutectic system was characterized by DSC and
the melting points obtained were used for the construction of a phase diagram.
The preservation of the characteristic PXRD patterns and the IR spectra of the
parent APIs, and the visualization of a characteristic eutectic lamellar
crystalline microstructure using Confocal Raman Microscopy confirm this system as
a true eutectic mixture. The PXRD result also confirms the amorphous nature of
the prepared solid solution. Theoretical chemical analyses indicate the
predominance of pi-stacking interactions in the amorphous solid solution, whereas
an electrostatic interaction between the APIs is responsible for maintaining the
alternating lamellar crystalline microstructure in the eutectic mixture. Both the
eutectic mixture and the amorphous solid solution happen to have a characteristic
PCZ to BNZ ratio similar to that of their pharmacological doses for treating
Chagas disease, thus providing a unique therapeutic combination dose with
enhanced apparent solubility and dissolution rate.
PMID- 28412453
TI - In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and
common laboratory animals.
AB - Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad
applications in manufacturing and history as an agent of warfare/terror highlight
the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a
pre-clinical antidote for cyanide poisoning, exploits an endogenous
detoxification pathway and should be amenable to mass-casualty scenarios. Because
human studies are unethical, determination of appropriate animal species as
models in translational studies for FDA approval under the "Animal Rule" are
critical. Here, we compared the specific activities of mercaptopyruvate
sulfurtransferase (MST, required for sulfanegen's activity), across common
laboratory models of cyanide intoxication, and humans. Human MST activities in
erythrocytes (measured as micromole pyruvate/min/106 rbc) were closest to those
of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more
detailed tissue-specific comparison of MST activities. NZW Rabbits were closest
to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster
mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse
was closest in the kidney cytosolic fraction. These data comparing MST activities
in animal models will help justify the use of those specific animals per the
animal rule. Interestingly, statistically significant differences were found in
MST activities of liver mitochondria between human smokers and non-smokers
(p=0.0030).
PMID- 28412454
TI - New insights into the toxicity of mineral fibres: A combined in situ synchrotron
MU-XRD and HR-TEM study of chrysotile, crocidolite, and erionite fibres found in
the tissues of Sprague-Dawley rats.
AB - Along the line of the recent research topic aimed at understanding the in vivo
activity of mineral fibres and their mechanisms of toxicity, this work describes
the morpho-chemical characteristics of the mineral fibres found in the tissues of
Sprague-Dawley rats subjected to intraperitoneal/intrapleural injection of UICC
chrysotile, UICC crocidolite and erionite-Na from Nevada (USA). The fibres are
studied with in situ synchrotron powder diffraction and high resolution
transmission electron microscopy to improve our understanding of the mechanisms
of toxicity of these mineral fibres. In contact with the tissues of the rats,
chrysotile fibres are prone to dissolve, with leaching of Mg and production of a
silica rich relict. On the other hand, crocidolite and erionite-Na fibres are
stable even for very long contact times within the tissues of the rats, showing
just a thin dissolution amorphous halo. These findings support the model of a
lower biopersistence of chrysotile with respect to crocidolite and erionite-Na
but the formation of a silica-rich fibrous residue after the pseudo-amorphization
of chrysotile may justify a higher cytotoxic potential and intense inflammatory
activity of chrysotile in the short term in contact with the lung tissues.
PMID- 28412455
TI - Effects of RF pulse profile and intra-voxel phase dispersion on MR fingerprinting
with balanced SSFP readout.
AB - PURPOSE: To investigate possible errors in T1 and T2 quantification via MR
fingerprinting with balanced steady-state free precession readout in the presence
of intra-voxel phase dispersion and RF pulse profile imperfections, using
computer simulations based on Bloch equations. MATERIALS AND METHODS: A pulse
sequence with TR changing in a Perlin noise pattern and a nearly sinusoidal
pattern of flip angle following an initial 180-degree inversion pulse was
employed. Gaussian distributions of off-resonance frequency were assumed for
intra-voxel phase dispersion effects. Slice profiles of sinc-shaped RF pulses
were computed to investigate flip angle profile influences. Following
identification of the best fit between the acquisition signals and those
established in the dictionary based on known parameters, estimation errors were
reported. In vivo experiments were performed at 3T to examine the results.
RESULTS: Slight intra-voxel phase dispersion with standard deviations from 1 to
3Hz resulted in prominent T2 under-estimations, particularly at large T2 values.
T1 and off-resonance frequencies were relatively unaffected. Slice profile
imperfections led to under-estimations of T1, which became greater as regional
off-resonance frequencies increased, but could be corrected by including slice
profile effects in the dictionary. Results from brain imaging experiments in vivo
agreed with the simulation results qualitatively. CONCLUSION: MR fingerprinting
using balanced SSFP readout in the presence of intra-voxel phase dispersion and
imperfect slice profile leads to inaccuracies in quantitative estimations of the
relaxation times.
PMID- 28412456
TI - Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin
cancer through enhanced repair of damaged DNA-dependent activation of immune
sensitivity.
AB - Numerous plant products have been used to prevent and manage a wide variety of
diseases for centuries. These products are now considered as promising options
for the development of more effective and less toxic alternatives to the systems
of medicine developed primarily in developed countries in the modern era. Grape
seed proanthocyanidins (GSPs) are of great interest due to their anti
carcinogenic effects that have been demonstrated using various tumor models
including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre
clinical mouse model supplementation of a control diet (AIN76A) with GSPs at
concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and
multiplicity of UVB radiation-induced skin tumors. In this review, we summarize
the evidence that this inhibition of UVB-induced skin tumor development by
dietary GSPs is mediated by a multiplicity of coordinated effects including: (i)
Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and
(ii) DNA repair-dependent stimulation of the immune system following the
functional activation of dendritic cells and effector T cells. Dietary GSPs hold
promise for the development of an effective alternative strategy for the
prevention of excessive solar UVB radiation exposure-induced skin diseases
including the risk of non-melanoma skin cancer in humans.
PMID- 28412457
TI - Identification and expression analysis of alternatively spliced new transcript
isoform of Bax gene in mouse.
AB - Bax, a pro-apoptotic member of Bcl-2 family regulates apoptosis through
homodimerization/heterodimerization with Bcl-2. Bax-alpha is the only product of
the Bax gene that has been extensively studied. Bax-alpha exists in inactive form
and several conformational changes are required during apoptosis to activate it.
Here, we have identified a novel transcript variant of Bax gene in mouse which
contains alternatively spliced new first exon that is different from the first
exon of previously reported transcript. Conceptual translation of new transcript
encodes a protein (Bax-alpha1), having different N-terminus. The existence of the
new transcript variant was confirmed by reverse transcriptase-PCR, semi-nested
PCR using primers designed for the newly identified transcript variant. The
identity of PCR product obtained after semi-nested PCR was confirmed by DNA
sequencing. Relative expression of new transcript variant with respect to
reported transcript was also studied with the help of real time PCR. The
existence of new transcript variant was further supported by the presence of
clusters of overlapping ESTs from the database. Bax-alpha1 possibly displays
heterogeneous properties as predicted by post-translational modification analysis
tools. The differences in post-translational modifications might play important
roles in divergent function of the new isoform. The three dimensional structure
was generated by homology modelling to visualize the differences at N termini of
known and newly identified variant.
PMID- 28412458
TI - Clinical significance of the B7-H4 as a novel prognostic marker in breast cancer.
AB - Increasing evidence has suggested that B7-H4 plays an important role in cancer
development not only in immune field. However, the correlation between B7-H4
protein expression and clinical outcome in primary breast cancer has not been
investigated. We examined the expression of B7-H4 by Immunohistochemistry in 147
cases of invasive breast carcinomas. Correlation of B7-H4 protein levels with
pathological tumor stages and overall survival rates of breast cancer patients
were also analyzed. Uni-and multivariate analyses methods were performed to
evaluate the prognostic value of B7-H4 expression levels. We found that different
expression levels of B7-H4 on breast cancer cells were significantly correlated
with patient's pTNM (pathological staging, T: primary tumor; N: regional lymph
node; M: distant metastasis) stage (P<0.001), overall survival (P=0.000), p53
(P=0.041). Furthermore, univariate analyses showed that the overall survival rate
of the patients with higher B7-H4 expression was significantly worse than that of
the patients with lower B7-H4 expression (P<0.001). Multivariate analyses showed
that B7-H4 was a significant independent prognostic indicator (P=0.000). Our
results suggest that B7-H4 might be closely associated with breast cancer
progression. Its high expression may serve as a potential prognostic biomarker in
human breast cancer.
PMID- 28412459
TI - No changes in heme synthesis in human Friedreich's ataxia erythroid progenitor
cells.
AB - Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced
expression of the protein frataxin. Frataxin is thought to play a role in iron
sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid
progenitor stem cells obtained from FRDA patients and healthy donors to
investigate the putative role, if any, of frataxin deficiency in heme synthesis.
We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA
quantification. We used atomic absorption spectrophotometry for iron levels and a
photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase
were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed
by a protein-protein interaction analysis was performed. FRDA patient cells
showed no significant changes in iron levels, hemoglobin synthesis,
protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis
presented 11 genes that were significantly changed in all patients compared to
controls. The genes are especially involved in oxidative stress, iron homeostasis
and angiogenesis. The mystery about the involvement of frataxin on iron
metabolism raises the question why frataxin deficiency in primary FRDA cells did
not lead to changes in biochemical parameters of heme synthesis. It seems that
alternative pathways can circumvent the impact of frataxin deficiency on heme
synthesis. We show for the first time in primary FRDA patient cells that reduced
frataxin levels are still sufficient for heme synthesis and possibly other
mechanisms can overcome reduced frataxin levels in this process. Our data
strongly support the fact that so far no anemia in FRDA patients was reported.
PMID- 28412460
TI - Characterization of transcriptome in the Indian meal moth Plodia interpunctella
(Lepidoptera: Pyralidae) and gene expression analysis during developmental
stages.
AB - The Indian meal moth Plodia interpunctella (Lepidoptera: Pyralidae) is a
worldwide pest that causes serious damage to stored foods. Although many efforts
have been conducted on this species due to its economic importance, the study of
genetic basis of development, behavior and insecticide resistance has been
greatly hampered due to lack of genomic information. In this study, we used high
throughput sequencing platform to perform a de novo transcriptome assembly and
tag-based digital gene expression profiling (DGE) analyses across four different
developmental stages of P. interpunctella (egg, third-instar larvae, pupae and
adult). We obtained approximate 9gigabyte (GB) of clean data and recovered 84,938
unigenes, including 37,602 clusters and 47,336 singletons. These unigenes were
annotated using BLAST against the non-redundant protein databases and then
functionally classified based on Gene Ontology (GO), Clusters of Orthologous
Groups (COG), and Kyoto Encyclopedia of Genes and Genomes databases (KEGG). A
large number of differentially expressed genes were identified by pairwise
comparisons among different developmental stages. Gene expression profiles
dramatically changed between developmental stage transitions. Some of these
differentially expressed genes were related to digestion and cuticularization.
Quantitative real-time PCR results of six randomly selected genes conformed the
findings in the DGEs. Furthermore, we identified over 8000 microsatellite markers
and 97,648 single nucleotide polymorphisms which will be useful for population
genetics studies of P. interpunctella. This transcriptomic information provided
insight into the developmental basis of P. interpunctella and will be helpful for
establishing integrated management strategies and developing new targets of
insecticides for this serious pest.
PMID- 28412461
TI - Effects of low-dose aspirin on maternal blood pressure and vascular function in
an experimental model of gestational hypertension.
AB - Daily intake of low-dose aspirin after 12weeks of gestation is currently
recommended as a preventative intervention in pregnancies in high risk of
developing preeclampsia. This recommendation is based on epidemiological
evidence, whereas experimental studies investigating the exact mechanisms of
aspirin action during pregnancy are lacking. We previously showed that treating
pregnant rats with a synthetic mimetic of unmethylated CpG DNA (bacterial DNA)
caused preeclampsia-like characteristics such as maternal hypertension and
increased cyclooxygenase (COX) expression and activity. In this study, we tested
the hypothesis that daily maternal treatment with low-dose aspirin would prevent
the development of maternal hypertension, reduce COX activity and thromboxane A2
(TxA2) production, and improve maternal vascular function in pregnant rats
exposed to CpG ODN during gestation. Pregnant rats were treated with ODN2395
(synthetic CpG DNA) or saline (vehicle) on gestational days (GD) 14, 16, 18.
Daily low-dose aspirin treatment (1.5mg/kgBW) started on GD10 and continued
throughout gestation. Pregnant rats treated with ODN2395 had greater systolic
blood pressure compared to controls (120+/-4mmHg vs. 100+/-5mmHg, p=0.03) and
aspirin did not prevent this increase (p=0.86). Aspirin prevented ODN2395-induced
increases of TxB2 (TxA2 metabolite) in serum and mesenteric arteries. ODN2395
increased expression of COX-1 and COX-2 in mesenteric and uterine arteries and
aspirin abolished these effects. Aspirin reduced contractile responses to
phenylephrine and U46619 (TxA2 mimetic) in mesenteric arteries from control rats
but not from ODN2395-treated rats. In conclusion, treatment with low-dose aspirin
reduced systemic and vascular COX expression and activity but did not prevent the
development of maternal hypertension induced by exposure to unmethylated CpG DNA
(bacterial DNA).
PMID- 28412462
TI - Spop regulates Gli3 activity and Shh signaling in dorsoventral patterning of the
mouse spinal cord.
AB - Sonic Hedgehog (Shh) signaling regulates the patterning of ventral spinal cord
through the effector Gli family of transcription factors. Previous in vitro
studies showed that an E3 ubiquitin ligase containing Speckle-type POZ protein
(Spop) targets Gli2 and Gli3 for ubiquitination and degradation, but the role of
Spop in Shh signaling and mammalian spinal cord patterning remains unknown. Here,
we show that loss of Spop does not alter spinal cord patterning, but it
suppresses the loss of floor plate and V3 interneuron phenotype of Gli2 mutants,
suggesting a negative role of Spop in Gli3 activator activity, Shh signaling and
the specification of ventral cell fates in the spinal cord. This correlates with
a moderate but significant increase in the level of Gli3 protein in the Spop
mutant spinal cords. Furthermore, loss of Spop restores the maximal Shh pathway
activation and ventral cell fate specification in the Gli1;Sufu double mutant
spinal cord. Finally, we show that loss of Spop-like does not change the spinal
cord patterning in either wild type or Spop mutants, suggesting that it does not
compensate for the loss of Spop in Shh signaling and spinal cord patterning.
Therefore, our results demonstrate a negative role of Spop in the level and
activity of Gli3, Shh signaling and ventral spinal cord patterning.
PMID- 28412463
TI - A methodological survey identified eight proposed frameworks for the adaptation
of health related guidelines.
AB - BACKGROUND AND OBJECTIVE: Our objective was to identify and describe published
frameworks for adaptation of clinical, public health, and health services
guidelines. METHODS: We included reports describing methods of adaptation of
guidelines in sufficient detail to allow its reproducibility. We searched Medline
and EMBASE databases. We also searched personal files, as well manuals and
handbooks of organizations and professional societies that proposed methods of
adaptation and adoption of guidelines. We followed standard systematic review
methodology. RESULTS: Our search captured 12,021 citations, out of which we
identified eight proposed methods of guidelines adaptation: ADAPTE, Adapted
ADAPTE, Alberta Ambassador Program adaptation phase, GRADE-ADOLOPMENT, MAGIC,
RAPADAPTE, Royal College of Nursing (RCN), and Systematic Guideline Review (SGR).
The ADAPTE framework consists of a 24-step process to adapt guidelines to a local
context taking into consideration the needs, priorities, legislation, policies,
and resources. The Alexandria Center for Evidence-Based Clinical Practice
Guidelines updated one of ADAPTE's tools, modified three tools, and added three
new ones. In addition, they proposed optionally using three other tools. The
Alberta Ambassador Program adaptation phase consists of 11 steps and focused on
adapting good-quality guidelines for nonspecific low back pain into local
context. GRADE-ADOLOPMENT is an eight-step process based on the GRADE Working
Group's Evidence to Decision frameworks and applied in 22 guidelines in the
context of national guideline development program. The MAGIC research program
developed a five-step adaptation process, informed by ADAPTE and the GRADE
approach in the context of adapting thrombosis guidelines. The RAPADAPTE
framework consists of 12 steps based on ADAPTE and using synthesized evidence
databases, retrospectively derived from the experience of producing a high
quality guideline for the treatment of breast cancer with limited resources in
Costa Rica. The RCN outlines five key steps strategy for adaptation of guidelines
to the local context. The SGR method consists of nine steps and takes into
consideration both methodological gaps and context-specific normative issues in
source guidelines. We identified through searching personal files two abandoned
methods. CONCLUSION: We identified and described eight proposed frameworks for
the adaptation of health-related guidelines. There is a need to evaluate these
different frameworks to assess rigor, efficiency, and transparency of their
proposed processes.
PMID- 28412465
TI - Authors of clinical trials reported individual and financial conflicts of
interest more frequently than institutional and nonfinancial ones: a
methodological survey.
AB - BACKGROUND AND OBJECTIVE: Conflicts of interest (COIs) are increasingly
recognized as important to disclose and manage in health research. The objective
of this study was to assess the reporting of both financial and nonfinancial COI
by authors of randomized controlled trials published in a representative sample
of clinical journals. METHODS: We searched Ovid Medline and included a random
sample of 200 randomized controlled trials published in 2015 in one of the 119
Core Clinical Journals. We classified COI using a comprehensive framework that
includes the following: individual COIs (financial, professional, scholarly,
advocatory, personal) and institutional COIs (financial, professional, scholarly,
and advocatory). We conducted descriptive and regression analyses. RESULTS: Of
the 200 randomized controlled trials, 188 (94%) reported authors' COI disclosures
that were available in the main document (92%) and as International Committee of
Medical Journal Editors forms accessible online (12%). Of the 188 trials, 57% had
at least one author reporting at least one COI; in all these trials, at least one
author reported financial COI. Institutional COIs (11%) and nonfinancial COIs
(4%) were less commonly reported. References to COI disclosure statements for
editors (1%) and medical writers (0%) were seldom present. Regression analyses
showed positive associations between reporting individual financial COI and
higher journal impact factor (odds ratio [OR] = 1.06, 95% confidence interval
[CI] = 1.02-1.10), larger number of authors (OR = 1.10, 95% CI 1.02-1.20),
affiliation with an institution from a high-income country (OR = 16.75, 95% CI
3.38-82.87), and trials reporting on pharmacological interventions (OR = 2.28,
95% CI 1.13-4.62). CONCLUSION: More than half of published randomized controlled
trials report that at least one author has a COI. Trial authors report financial
COIs more often than nonfinancial COIs and individual COIs more frequently than
institutional COIs.
PMID- 28412464
TI - GRADE equity guidelines 1: considering health equity in GRADE guideline
development: introduction and rationale.
AB - OBJECTIVES: This article introduces the rationale and methods for explicitly
considering health equity in the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) methodology for development of clinical,
public health, and health system guidelines. STUDY DESIGN AND SETTING: We
searched for guideline methodology articles, conceptual articles about health
equity, and examples of guidelines that considered health equity explicitly. We
held three meetings with GRADE Working Group members and invited comments from
the GRADE Working Group listserve. RESULTS: We developed three articles on
incorporating equity considerations into the overall approach to guideline
development, rating certainty, and assembling the evidence base and evidence to
decision and/or recommendation. CONCLUSION: Clinical and public health guidelines
have a role to play in promoting health equity by explicitly considering equity
in the process of guideline development.
PMID- 28412466
TI - Proposed variations of the stepped-wedge design can be used to accommodate
multiple interventions.
AB - OBJECTIVES: Stepped-wedge design (SWD) cluster-randomized trials have
traditionally been used for evaluating a single intervention. We aimed to explore
design variants suitable for evaluating multiple interventions in an SWD trial.
STUDY DESIGN AND SETTING: We identified four specific variants of the traditional
SWD that would allow two interventions to be conducted within a single cluster
randomized trial: concurrent, replacement, supplementation, and factorial SWDs.
These variants were chosen to flexibly accommodate study characteristics that
limit a one-size-fits-all approach for multiple interventions. RESULTS: In the
concurrent SWD, each cluster receives only one intervention, unlike the other
variants. The replacement SWD supports two interventions that will not or cannot
be used at the same time. The supplementation SWD is appropriate when the second
intervention requires the presence of the first intervention, and the factorial
SWD supports the evaluation of intervention interactions. The precision for
estimating intervention effects varies across the four variants. CONCLUSION:
Selection of the appropriate design variant should be driven by the research
question while considering the trade-off between the number of steps, number of
clusters, restrictions for concurrent implementation of the interventions,
lingering effects of each intervention, and precision of the intervention effect
estimates.
PMID- 28412467
TI - Magnitude and direction of missing confounders had different consequences on
treatment effect estimation in propensity score analysis.
AB - OBJECTIVE: Propensity score (PS) analysis allows an unbiased estimate of
treatment effects but assumes that all confounders are measured. We assessed the
impact of omitting confounders from a PS analysis on clinical decision making.
STUDY DESIGN AND SETTING: We conducted Monte Carlo simulations on hypothetical
observational studies based on virtual populations and on the population from a
large randomized trial (CRASH-2). In both series of simulations, PS analysis was
conducted with all confounders and with omitted confounders, which were defined
to have different strengths of association with the outcome and treatment
exposure. After inverse probability of treatment weighting, we calculated the
absolute risk differences and numbers needed to treat (NNT). RESULTS: In both
series of simulations, omitting a confounder that was moderately associated with
the outcome and exposure led to negligible bias on the NNT scale. The bias
induced by omitting strongly positive confounding variables remained less than 15
patients to treat. Major bias and reversed effects were found only when omitting
highly prevalent, strongly negative confounders that were similarly associated
with the outcome and exposure with odds ratios greater than 4.00 (or <0.25). This
omission was accompanied by a substantial decrease in analysis power. CONCLUSION:
The omission of strongly negative confounding variables from a PS analysis can
lead to incorrect clinical decision making. However, omitting these variables
also decreases the analysis power, which may prevent the reporting of significant
but misleading effects.
PMID- 28412468
TI - A computationally simple central monitoring procedure, effectively applied to
empirical trial data with known fraud.
AB - OBJECTIVES: Central monitoring of multicenter clinical trials becomes an ever
more feasible quality assurance tool, in particular for the detection of data
fabrication. More widespread application, across both industry sponsored as well
as academic clinical trials, requires central monitoring methodologies that are
both effective and relatively simple in implementation. STUDY DESIGN AND SETTING:
We describe a computationally simple fraud detection procedure intended to be
applied repeatedly and (semi-)automatically to accumulating baseline data and to
detect data fabrication in multicenter trials as early as possible. The procedure
is based on anticipated characteristics of fabricated data. It consists of seven
analyses, each of which flags approximately 10% of the centers. Centers that are
flagged three or more times are considered "potentially fraudulent" and require
additional investigation. The procedure is illustrated using empirical trial data
with known fraud. RESULTS: In the illustration data, the fraudulent center is
detected in most repeated applications to the accumulating trial data, while
keeping the proportion of false-positive results at sufficiently low levels.
CONCLUSION: The proposed procedure is computationally simple and appears to be
effective in detecting center-level data fabrication. However, assessment of the
procedure on independent trial data sets with known data fabrication is required.
PMID- 28412470
TI - Crosstalk between kidney and bone - Bench to bedside.
PMID- 28412469
TI - Earliest phases of chondrogenesis are dependent upon angiogenesis during ectopic
bone formation in mice.
AB - Endochondral ossification is the process where cartilage forms prior to
ossification and in which new bone forms during both fracture healing and ectopic
bone formation. Transitioning to ossification is a highly coordinated process
between hypertrophic chondrocytes, vascular endothelial cells, osteoblasts and
osteoclasts. A critical biological process that is central to the interactions of
these various cell types is angiogenesis. Although it is well established that
angiogenesis is crucial for fracture repair, less is known pertaining to the role
of angiogenesis in ectopic bone formation. Furthermore, fracture repair models
are complicated by extensive trauma, subsequent inflammatory responses and
concurrent repair processes in multiple tissues. In order to more definitively
characterize the relationship between angiogenesis and postnatal endochondral
ossification, a model of ectopic bone formation was used. Human demineralized
bone matrix (DBM) was implanted in immune-deficient mice (rag null (B6.129S7
Rag1tm1/MOM/J)) to induce ectopic bone. Inhibition of angiogenesis with either a
small molecule (TNP-470) or a targeted biological (Vascular Endothelial Growth
Factor Receptor type 2 [VEGFR2] blocking antibody) prevented ectopic bone
formation by 83% and 77%, respectively. Most striking was that the progression of
chondrogenesis was halted during very early phases of chondrocyte differentiation
between condensation and prehypertrophy (TNP-470) or the proliferative phase
(VEGFR2 blockade) prior to hypertrophy, while osteoclast recruitment and
resorption were almost completely inhibited. Our results demonstrate angiogenesis
plays a developmental role in endochondral bone formation at a much earlier phase
of chondrogenesis than suggested by prior findings.
PMID- 28412471
TI - Surface modification of solid lipid nanoparticles for oral delivery of curcumin:
Improvement of bioavailability through enhanced cellular uptake, and lymphatic
uptake.
AB - Curcumin has been reported to exhibit potent anticancer effects. However, poor
solubility, bioavailability and stability of curcumin limit its in vivo efficacy
for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising
delivery system for the enhancement of bioavailability of hydrophobic drugs.
However, burst release of drug from SLN in acidic environment limits its usage as
oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated
curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic
environment and enhance the bioavailability. The NCC-SLN exhibited suppressed
burst release in simulated gastric fluid while sustained release was observed in
simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity
and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability
of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin
solution, respectively. These results suggest that NCC-SLN could be an efficient
oral delivery system for curcumin.
PMID- 28412472
TI - Preparation and characterization of dutasteride-loaded nanostructured lipid
carriers coated with stearic acid-chitosan oligomer for topical delivery.
AB - Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair
growth. To enhance delivery to the hair follicles and reduce systemic effects, in
this study dutasteride has been formulated for topical application, in a
nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid
(CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1H NMR and
FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs)
was optimized using a 23 full factorial design. This formulation was coated with
different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with
5% SA-CSO increased mean size from 187.6+/-7.0nm to 220.1+/-11.9nm, and modified
surface charge, with zeta potentials being -18.3+/-0.9mV and +25.8+/-1.1mV for
uncoated and coated DST-NLCs respectively. Transmission electron microscopy
showed all formulations comprised approximately spherical particles. DST-NLCs,
coated and uncoated with CSO-SA, exhibited particle size stability over 60days,
when stored at 4-8 degrees C. However, NLCs coated with CSO (without conjugation)
showed aggregation when stored at 4-8 degrees C after 30days. The measured
particle size for all formulations stored at 25 degrees C suggested aggregation,
which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All
nanoparticle formulations exhibited rapid release in an in vitro release study,
with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion
cell, no dutasteride permeated through pig ear skin after 48h, such that it was
not detected in the receptor chamber for all samples. The amount of dutasteride
in the skin was significantly different (p<0.05) for DST-NLCs (6.09+/
1.09MUg/cm2) without coating and those coated with 5% CSO-SA (2.82+/
0.40MUg/cm2), 10% CSO-SA (2.70+/-0.35MUg/cm2) and CSO (2.11+/-0.64MUg/cm2). There
was a significant difference (p<0.05) in the cytotoxicity (IC50) between
dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO
SA increased the maximum non-toxic concentration by 20-fold compared to
dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate
was successfully prepared, and modified the surface charge of DST-NLCs from
negative to positive. These stable, less cytotoxic, positively-charged
dutasteride-loaded nanostructured lipid carriers, with stearic acid-chitosan
oligomer conjugate, are appropriate for topical delivery and have potential for
promotion of hair growth.
PMID- 28412473
TI - Nanoformulations for dimethyl fumarate: Physicochemical characterization and in
vitro/in vivo behavior.
AB - Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple
sclerosis treatment (Tecfidera(r)). Nevertheless, since Tecfidera(r) capsules
induce flushing, gastro-intestinal events and other more serious drawbacks, in
this investigation a nanoparticle based system to be administered by an
alternative way is proposed. In particular this study describes the preparation
and characterization of dimethyl fumarate-containing solid lipid nanoparticles
(SLN). Namely SLN based on tristearin, tristearin SLN treated with polysorbate 80
and cationic SLN constituted of tristearin in mixture with
dimethyldioctadecylammonium chloride were investigated. The effect of the
presence of dimethyl fumarate, functionalization by polysorbate 80 and
dimethyldioctadecylammonium chloride was studied on morphology and dimensional
distribution of SLN, by photon correlation spectroscopy and cryogenic
transmission electron microscopy. Dimethyl fumarate release from SLN, studied by
Franz cell, evidenced a Fickian dissolutive type kinetic in the case of SLN
treated by polysorbate 80. Moreover fluorescent SLN were produced and
characterized in order to investigate their in vitro permeability and in vivo
biodistribution in mice. An in vitro study of fluorescent SLN permeability
performed through a model of mouse brain microvascular endothelial cells,
indicated that cationic SLN displayed higher permeability values with respect to
neutral SLN and SLN treated by polysorbate 80. Biodistribution of polysorbate 80
treated SLN was studied by fluorescent imaging after intraperitoneal or
intranasal administration in mice. The in vivo images indicate that polysorbate
80 treated SLN were able to reach the brain, even if they prevalently accumulated
in liver and spleen, especially by intraperitoneal route.
PMID- 28412474
TI - Kinetics for Drug Discovery: an industry-driven effort to target drug residence
time.
AB - A considerable number of approved drugs show non-equilibrium binding
characteristics, emphasizing the potential role of drug residence times for in
vivo efficacy. Therefore, a detailed understanding of the kinetics of association
and dissociation of a target-ligand complex might provide crucial insight into
the molecular mechanism-of-action of a compound. This deeper understanding will
help to improve decision making in drug discovery, thus leading to a better
selection of interesting compounds to be profiled further. In this review, we
highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium,
which targets major open questions related to binding kinetics in an industry
driven public-private partnership.
PMID- 28412476
TI - Monoclonal gammopathy of undetermined significance and biological treatments:
What should we do?
PMID- 28412475
TI - Potential anti-inflammatory effect of LQFM-021 in carrageenan-induced
inflammation: The role of nitric oxide.
AB - The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti
inflammatory activities. Furthermore, it has low toxicity, indicating that this
compound may be considered to be a good prototype for the development of new
analgesic/anti-inflammatory drugs. Therefore, the aim of this study was to
investigate the potential anti-inflammatory activity of LQFM-021 using a model of
carrageenan-induced inflammation as well as the mechanism of action and role of
nitric oxide in this effect. Acute treatments with LQFM-021 (30 and 60 mg/kg
p.o.) reduced paw edema formation dose-dependently 2 h after carrageenan
injection. In the carrageenan-induced pleurisy test, LQFM-021 (30 mg/kg p.o.)
reduced the leukocyte (polymorphonuclear) count in the pleural cavity, as well as
decreased protein extravasation and myeloperoxidase activity. This dose of LQFM
021 increased the NO (nitrite/nitrate) and IL-4 levels and decreased the TNF
alpha and IL-1beta levels in the pleural cavity. Moreover, pre-treatment with L
NAME reversed the effect of LQFM-021 on NO, leukocyte migration, and the TNF
alpha and IL-1beta levels. Additionally, we observed that LQFM-021 showed weak
inhibitory activity on cyclooxygenases, but reduced the PGE2 levels in the
pleural cavity. Immunoblot analyses showed that LQFM-021 promoted a decrease in
COX-2 levels and increase in iNOS levels. In conclusion, we demonstrated that
LQFM-021 has marked anti-inflammatory activity by reducing polymorphonuclear
recruitment, which is associated with the inhibition of the production of
inflammatory cytokines and eicosanoids. In addition, we found that the
synthase/release of nitric oxide promoted by LQFM-021 is essential for the anti
inflammatory effect observed.
PMID- 28412477
TI - Impact of major life events on breast-cancer-specific mortality: A case fatality
study on 8000 breast cancer patients.
AB - BACKGROUND: It has been suggested that long-term activation of the body's stress
response system and subsequent overexposure to stress hormones may be associated
with increased morbidity. However, evidence on the impact of major life events on
mortality from breast cancer (BC) remains inconclusive. The main aim of this
study is to investigate whether major negatively or positively experienced life
events before or after diagnosis have an effect on BC-specific mortality in women
who have survived with BC for at least 2 years. METHODS: We conducted a case
fatality study with data on life events from a self-administered survey and data
on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC
mortality hazard ratios (MRs) between those who have undergone major life events
and those who haven't. RESULTS: None of the pre-diagnostic negative life events
had any effect on BC-specific mortality. Regarding post-diagnostic events, the
effect was greatest in women with moderate scores of events. As for event
specific scores, increased BC mortality was observed with spouse unemployment,
relationship problems, and death of a close friend. By contrast, falling in love
and positive developments in hobbies were shown to be associated with lower BC
mortality (MRs 0.67, 95%CI: 0.49-0.92 and 0.74, 95%CI: 0.57-0.96, respectively).
In an analysis restricted to recently diagnosed cases (2007), also death of a
child and of a mother was associated with increased BC mortality. CONCLUSIONS:
Some major life events regarding close personal relationships may play a role in
BC-specific mortality, with certain negative life events increasing BC mortality
and positive events decreasing it. The observed favorable associations between
positive developments in romantic relationships and hobbies and BC mortality are
likely to reflect the importance of social interaction and support.
PMID- 28412478
TI - Mitochondrial and peroxisomal Lon proteases play opposing roles in reproduction
and growth but co-function in the normal development, stress resistance and
longevity of Thermomyces lanuginosus.
AB - The ATP-dependent Lon enzyme is a highly conserved protease with multiple roles
in diverse species such as fungi; however, there are few reports on Lon enzymes
in filamentous fungi. Thermomyces lanuginosus, a typical thermophilic fungus, has
been widely studied in physiology and cell biology; thus, studies on Thermomyces
Lons are important. Two Lons were bioinformatically deduced in T. lanuginosus.
Subcellular localization analysis showed that one is present in mitochondria
(MLon), while the other is found in peroxisomes (PLon). Although both Lon enzymes
were activated by H2O2, they were not induced by heat shock; instead, they were
induced by low temperatures. Two single-deletion Lon mutants (DeltaMLon and
DeltaPLon) were generated. Biological analysis demonstrated that DeltaMLon
decreased the production of conidia but increased the growth of mycelia. By
contrast, DeltaPLon increased the production of conidia but decreased the growth
of mycelia. The lifespan was measured in time and in length of continuous growth.
The wild-type strain showed continuous linear growth for 60days, whereas growth
was impeded at 30 and 50days for DeltaPLon and DeltaMLon mutants, respectively,
suggesting that PLon is more important for longevity than MLon. Interestingly,
DeltaPLon, which accumulated larger amount of H2O2 was not only more sensitive to
exogenous H2O2 but also much more sensitive to other selected stressors. Taken
together, our data indicate that mitochondrial and peroxisomal Lons play opposite
roles in controlling growth and development, but exhibit synergistic effects on
the normal states of vegetative growth, asexual development, stress resistance
and longevity in T. lanuginosus.
PMID- 28412479
TI - Cough in exercise and athletes.
AB - Cough is the most common respiratory symptom reported by athletes and can
significantly impact on health status, ability to train and athletic performance.
The presence of cough in an athlete is typically taken to indicate exercise
induced bronchoconstriction (EIB), yet in many athletes with chronic cough there
is no objective evidence of airway hyper-responsiveness (AHR) or heightened
airway inflammation. Moreover, cough in athletes often fails to respond to a
therapeutic asthma strategy, thus further work is urgently needed to progress our
understanding of the pathophysiology of exercise-associated cough in this unique
population. This article provides an overview of the current state of knowledge
of exercise-associated cough in athletes. The article summarises our
understanding of pathophysiological basis of cough in this context and provides a
pragmatic clinical approach to this problem.
PMID- 28412480
TI - Retraction of Neurosurgical Publications: A Systematic Review.
AB - OBJECTIVES: Despite the increasing awareness of scientific fraud, no attempt has
been made to assess its prevalence in neurosurgery. The aim of our review was to
assess the chronologic trend, reasons, research type/design, and country of
origin of retracted neurosurgical publications. METHODS: Three independent
reviewers searched the EMBASE and MEDLINE databases using neurosurgical keywords
for retracted articles from 1995 to 2016. Archives of retracted articles
(retractionwatch.com) and the independent Web sites of neurosurgical journals
were also searched. Data including the journal, impact factor, reason for
retraction, country of origin, and citations were extracted. RESULTS: A total of
97 studies were included for data extraction. Journal impact factor ranged from
0.57 to 35.03. Most studies (61) were retracted within the last 5 years. The most
common reason for retraction was because of a duplicated publication found
elsewhere (26), followed closely by plagiarism (22), or presenting fraudulent
data (14). Other reasons included scientific errors/mistakes, author
misattribution, and compromised peer review. Articles originated from several
countries and some were widely cited. CONCLUSIONS: Retractions of neurosurgical
publications are increasing significantly, mostly because of issues of academic
integrity, including duplicate publishing and plagiarism. Implementation of more
transparent data-sharing repositories and thorough screening of data before
manuscript submission, as well as additional educational programs for new
researchers, may help mitigate these issues in the future.
PMID- 28412481
TI - Environmental and Clinical Risk Factors for Delirium in a Neurosurgical Center: A
Prospective Study.
AB - BACKGROUND: Few reports of delirium-related risk factors have focused on
environmental risk factors and clinical risk factors, such as white matter signal
abnormalities on magnetic resonance imaging fluid attenuated inversion recovery
images. METHODS: We prospectively enrolled 253 patients admitted to our
neurosurgical center between December 2014 and June 2015 and analyzed 220
patients (100 male patients; mean age, 64.1 years; age range, 17-92 years). An
Intensive Care Delirium Screening Checklist score >=4 points indicated delirium.
We evaluated patient factors consisting of baseline characteristics and related
factors, such as white matter lesions (WMLs), as well as the surrounding
environment. RESULTS: Delirium occurred in 29/220 cases (13.2%). Regarding
baseline characteristics, there were significant statistical correlations between
delirium and age (P = 0.0187), Hasegawa Dementia Scale-Revised score (P = 0.0022)
on admission, and WMLs (P < 0.0001). WMLs were related to age (P < 0.0001) and
atherosclerotic disease (P = 0.004). Regarding related factors, there were
significant statistical correlations between delirium and stay in a neurosurgical
care unit (P = 0.0245). Multivariate logistic regression analyses showed
statistically significant correlations of delirium with WMLs (P < 0.0001) and
surrounding patients with delirium (P = 0.026). CONCLUSIONS: WMLs in patients and
the surrounding environment are risk factors for delirium in a neurosurgical
center. To prevent delirium, clinicians must recognize risk factors, such as high
grade WMLs, and manage environmental factors.
PMID- 28412482
TI - Dapagliflozin-citric acid cocrystal showing better solid state properties than
dapagliflozin.
AB - Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2
inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO
H2O, 1:1:1) is the solid form used in the current tablet product to address the
severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the
problem of instability when exposed to high temperature, which renders it
amorphous. In this work, we report on the preparation and evaluation of a new 1:1
cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits
superior stability against high temperature and high relative humidity without
compromising dissolution and tableting performance. Thus, DAP-CA is a promising
solid form for developing the next generation DAP tablet products with improved
performance.
PMID- 28412483
TI - Effect of micro-environment modification and polymer type on the in-vitro
dissolution behavior and in-vivo performance of amorphous solid dispersions.
AB - This study investigates the effects of micro-environment modification and polymer
type on the in-vitro dissolution behavior and in-vivo performance of micro
environment pH modifying solid dispersions (pHM-SD) for the poorly water-soluble
model drug Toltrazuril (TOL). Various pHM-SDs were prepared using Ca(OH)2 as a pH
modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000),
polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based
on the results of physicochemical characterizations and in-vitro dissolution
testing, the representative ternary (Ca(OH)2:TOL:PEG6000/HPMC/PVPk30=1:8:24,
w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and
optimized to perform in-vivo pharmacokinetic study. The micro-environment pH
modification improved the in-vitro water-solubility and in-vivo bioavailability
of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the
release and absorption of prototype drug, but also promoted the generation of
active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril
sulfone (TOLSO2). The in-vitro dissolution profiles and in-vivo absorption,
distribution and metabolism behaviors of the pHM-SDs varied with polymer type.
Moreover, in-vivo bioavailability of three active pharmaceutical ingredients
increased with an increase in in-vitro dissolution rates of the drug from the pHM
SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution
method can be used to predict the in-vivo performance of pHM-SDs formulated with
various polymers with trend consistency. In-vitro and in-vivo screening
procedures revealed that the pHM-SD composed of Ca(OH)2, TOL and PVPk30 at a
weight ratio of 1:8:24, of which the safety was adequately proved via
histopathological examination, may be a promising candidate for providing better
clinical outcomes.
PMID- 28412484
TI - Impact of demographics and disease progression on the relationship between
glucose and HbA1c.
AB - CONTEXT: Several studies have shown that the relationship between mean plasma
glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations.
Especially race has previously been referred to shift the regression line that
links MPG to HbA1c at steady-state (Herman & Cohen, 2012). OBJECTIVE: To assess
the influence of demographic and disease progression-related covariates on the
intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.
DATA: Longitudinal patient-level data from 16 late-phase trials in type 2
diabetes with a total of 8927 subjects was used to study covariates for the
relationship between MPG and HbA1c. The analysed covariates included age group,
BMI, gender, race, diabetes duration, and pre-trial treatment. Differences
between trials were taken into account by estimating a trial-to-trial variability
component. PARTICIPANTS: Participants included 47% females and 20% above 65years.
77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were
analysed together as other races. ANALYSIS: Estimates of the change in the
intercept of the MPG-HbA1c relationship due to the mentioned covariates were
determined using a longitudinal model. RESULTS: The analysis showed that pre
trial treatment with insulin had the most pronounced impact associated with a
0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group
also had an impact on the MPG-HbA1c relationship. CONCLUSION: Our analysis shows
that the relationship between MPG and HbA1c is relatively insensitive to
covariates, but shows small variations across populations, which may be relevant
to take into account when predicting HbA1c response based on MPG measurements in
clinical trials.
PMID- 28412485
TI - Cancer nanotheranostics: A review of the role of conjugated ligands for
overexpressed receptors.
AB - Cancer treatment using chemotherapy has many drawbacks because of its non
specificity, in which the chemotherapeutic agent attacks both normal and
cancerous cells, leading to severe damage to the normal cells, especially rapidly
proliferating ones. Cancer targeting enables the drug to kill only tumor cells
without adversely affecting healthy tissues, which leads to the improvement of
the patient's well-being. Nanoparticles offer several advantages in drug delivery
such as enhancing the solubility of hydrophobic drugs, sustaining their release
and prolonging their circulation time. The ability of nanoparticles to
specifically target tumor cells makes them a useful delivery system for
anticancer agents. The type of the delivery system and formulation additives used
can also improve the delivery of the anticancer agent. This review highlights
some of the most highly sought receptors to be targeted in selective cancer
treatment. It also reports some of the recent advances in cancer targeting using
drug-loaded ligand-conjugated nanocarriers.
PMID- 28412486
TI - Removal of toxic metals from vanadium-contaminated soils using a washing method:
Reagent selection and parameter optimization.
AB - Vanadium (V) contamination in soils is an increasing worldwide concern facing
human health and environmental conservation. The fractionation of a metal
influences its mobility and biological toxicity. We analyzed the fractionations
of V and several other metals using the BCR three-step sequential extraction
procedure. Among methods for removing metal contamination, soil washing is an
effective permanent treatment. We conducted experiments to select the proper
reagents and to optimize extraction conditions. Citric acid, tartaric acid,
oxalic acid, and Na2EDTA all exhibited high removal rates of the extractable
state of V. With a liquid-to-solid ratio of 10, washing with 0.4 mol/L citric
acid, 0.4 mol/L tartaric acid, 0.4 mol/L oxalic acid, and 0.12 mol/L Na2EDTA led
to removal rates of 91%, 88%, 88%, and 61%, respectively. The effect of multiple
washing on removal rate was also explored. According to the changes observed in
metal fractionations, differences in removal rates among reagents is likely
associated with their pKa value, pH in solution, and chemical structure. We
concluded that treating with appropriate washing reagents under optimal
conditions can greatly enhance the remediation of vanadium-contaminated soils.
PMID- 28412487
TI - Occurrence, homologue patterns and source apportionment of short- and medium
chain chlorinated paraffins in suburban soils of Shanghai, China.
AB - In order to systematically investigate the spatial distribution, homologue
profiles, and sources of short- and medium-chain chlorinated paraffins (SCCPs and
MCCPs) in suburban soils in Shanghai, SCCPs and MCCPs in soils were analyzed
using gas chromatography coupled with low resolution mass spectrometry in
electron capture negative ion (ECNI) mode (GC-ECNI-MS). The CP concentrations in
soils were between not detected (ND) - 697 ng g-1 with a median value of 3.52 ng
g-1 for SCCPs, and ND - 666 ng g-1 with a median value of 15.3 ng g-1 for MCCPs,
respectively. The concentrations of MCCPs in most soils were higher than that of
SCCPs. The total CP concentrations (sum of SCCPs and MCCPs) in soils varied from
ND to 964 ng g-1 with a median value of 20.5 ng g-1. The concentration of MCCPs
was higher than that of SCCPs in most soils. The levels of SCCPs and MCCPs in
suburban soils in Shanghai were at the medium level when compared to other areas
around the world. No significant correlation was observed between soil CP
concentrations and total organic carbon contents (p > 0.05). For different use
type of soils, the median concentrations of CPs in soils were found higher in
greenland than that in other areas probably due to busy traffic, sewage sludge
application and/or wastewater irrigation. All soils were divided into two groups
by hierarchical cluster analysis (HCA) both for SCCPs and MCCPs. Three discharge
sources of CPs in suburban soil of Shanghai were identified by PMF model.
PMID- 28412488
TI - In vitro cytotoxicity of decabrominated diphenyl ether (PBDE-209) to human red
blood cells (hRBCs).
AB - This work presents the effect of decabrominated diphenyl ether (PBDE-209) on the
anti-oxidative defense capacity, and ATPase activity (structure and function) of
human red blood cells (hRBCs). The results show that the PBDE-209 influences the
activity and content of typical biomolecules (SOD, CAT, GSH-Px, GSH and MDA) in
hRBCs, causing a decline in the function of the antioxidant defense system. The
PBDE-209 with a concentration of 10 MUmol/L resulted in the cytoplasmic
projections and structure deformation of the hRBCs. When its concentration
exceeds 25 MUmol/L, the relative ATPase activity was decreased to 20% of the
initial activity. Since the discovered effects of PBDE-209 on hRBCs are in cell
level, this study may offer some information to advise the related in vivo
cytotoxicity works.
PMID- 28412489
TI - Bimetallic AgCu/Cu2O hybrid for the synergetic adsorption of iodide from
solution.
AB - To further improve the capacity of Cu2O to absorb I- anions from solution, and to
understand the difference between the adsorption mechanisms of Ag/Cu2O and
Cu/Cu2O adsorbents, bimetallic AgCu was doped into Cu2O through a facile
solvothermal route. Samples were characterized and employed to adsorb I- anions
under different experimental conditions. The results show that the Cu content can
be tuned by adding different volumes of Ag sols. After doping bimetallic AgCu,
the adsorption capacity of the samples can be increased from 0.02 mmol g-1 to
0.52 mmol g-1. Moreover, the optimal adsorption is reached within only 240 min.
Meanwhile, the difference between the adsorption mechanisms of Ag/Cu2O and
Cu/Cu2O adsorbents was verified, and the cooperative adsorption mechanism of the
AgCu/Cu2O hybrid was proposed and verified. In addition, the AgCu/Cu2O hybrid
showed excellent selectivity, e.g., its adsorption efficiencies are 85.1%, 81.9%,
85.9% and 85.7% in the presence of the Cl-, CO32-, SO42- and NO3- competitive
anions, respectively. Furthermore, the AgCu/Cu2O hybrid can worked well in other
harsh environments (e.g., acidic, alkaline and seawater environments). Therefore,
this study is expected to promote the development of Cu2O into a highly efficient
adsorbent for the removal of iodide from solution.
PMID- 28412490
TI - Serpentine soils affect heavy metal tolerance but not genetic diversity in a
common Mediterranean ant.
AB - Natural habitats with serpentine soils are rich in heavy metal ions, which may
significantly affect ecological communities. Exposure to metal pollutants
results, for instance, in a reduction of population genetic diversity and a
diffused higher tolerance towards heavy metals. In this study, we investigated
whether chronic exposure to metals in serpentine soils affect accumulation
patterns, tolerance towards metal pollutants, and genetic diversity in ants. In
particular, we studied colonies of the common Mediterranean ant, Crematogaster
scutellaris, along a contamination gradient consisting of two differently
contaminated forests and a reference soil with no geogenic contamination. We
first evaluated the metal content in both soil and ants' body. Then, we tested
for tolerance towards metal pollutants by evaluating the mortality of ants fed
with nickel (Ni) solutions of increasing concentrations. Finally, differences in
genetic diversity among ants from different areas were assessed using eight
microsatellite loci. Interestingly, a higher tolerance to nickel solutions was
found in ants sampled in sites with intermediate levels of heavy metals. This may
occur, because ants inhabiting strongly contaminated areas tend to accumulate
higher amounts of contaminants. Additional ingestion of toxicants beyond the
saturation threshold would lead to death. There was no difference in the genetic
diversity among ant colonies sampled in different sites. This was probably the
result of queen mediated gene flow during nuptial flights across uncontaminated
and contaminated areas of limited geographical extent.
PMID- 28412491
TI - Rapid degradation of atrazine by hydroxyl radical induced from montmorillonite
templated subnano-sized zero-valent copper.
AB - In this study, subnano-sized zero-valent copper (ZVC) was synthesized using
montmorillonite clay mineral as the template. The discrete distribution of
surface charge on montmorillonite effectively separates the formed ZVC particles
and inhibits their aggregation. X-ray diffraction result indicates that the size
of ZVC particles on montmorillonite is ~6 A, which is much smaller than nano-ZVC
prepared by conventional method. The montmorillonite templated ZVC (ZVCMMT) shows
superior reactivity as indicated by the degradation of atrazine, over 90%
atrazine (15 MUM) could be degraded in a few min. Hydroxyl radical is confirmed
as the reactive species, which is produced from the activation of oxygen by ZVC.
It was also shown that the degradation process is strongly dependent on the
hydration status of synthesized ZVCMMT. The freeze dried ZVCMMT exhibits higher
reactivity compared to freshly prepared ZVCMMT, which can be explained by the
higher adsorption of atrazine and oxygen residue on freeze dried ZVCMMT surface.
In addition, the toxicity of atrazine is significantly decreased after the
reaction with ZVCMMT, indicating that ZVCMMT could be used as a promising
material for rapid remediation of persistent organic contaminants.
PMID- 28412492
TI - Element variability in lacustrine systems of Terra Nova Bay (Antarctica) and
concentration evolution in surface waters.
AB - Major, minor and trace elements were determined in freshwater of lacustrine
systems in Terra Nova Bay, along Victoria Land coast, Antarctica, as well as in
algae and mosses. The samples were collected during some of the sampling
campaigns between 2007 and 2011 (and the one of 2002) within the framework of the
Italian National Program of Research in Antarctica (PNRA). Data were processed
with chemometric techniques. Results showed that elements typically considered as
potential anthropogenic pollutants (e.g. As, Pb, Zn, Cu and Ni) present a strong
correlation with the lithogenic elements (e.g. Al, Si, Fe) in all matrices,
suggesting that their origin is connected to natural phenomena. Metal
concentrations in vegetation samples are in the same range as previously
published data. The obtained results were compared with older literature data
(since the early '90s) from the same lacustrine systems, in order to present a
historical overview of element concentrations. This approach furnishes important
information on surface water evolution as a function of time. A considerable
variability was observed in metal concentrations but no clear trend was
identified. This suggests that their concentration evolution is hardly correlated
to specific natural or anthropic phenomena. No evidence of an increase of
concentrations over time was apparent. Our results represent new important data
about metal concentrations in lacustrine systems in Antarctica, furnishing ranges
of values that can be considered as a reference. These data, therefore, could be
used to detect or monitor future local and/or global anthropogenic
contaminations.
PMID- 28412493
TI - The clinical impact and prevalence of emergency point-of-care ultrasound: A
prospective multicenter study.
AB - OBJECTIVE: The main objectives of our study were to evaluate the prevalence of
emergency point-of-care ultrasound (POCUS) use and to assess the impact of POCUS
on: diagnostic, therapeutic, patient orientation and imaging practices. METHODS:
This was a one-day, prospective, observational study carried out across multiple
centers. Fifty emergency departments (EDs) recorded all POCUS performed over a
24h period. The prevalence of POCUS was defined as the number of POCUS/number of
patients seen in all units. The "diagnostic impact" was defined as a POCUS
induced confirmation or change to the initial clinical diagnosis. The
"therapeutic impact" was defined as a POCUS-induced change in treatment. The
"orientation impact" was defined as an ultrasound-induced confirmation or change
in the initial orientation. The "imaging change" was defined as a radiologic
imaging prescription modification. RESULTS: Two hundred and twenty-nine (5%)
POCUS were performed on 192 patients (4%) from among the 4671 patients seen on
the study day in the 50 EDs. No ultrasound procedural guidance was given during
the study day. The diagnostic, therapeutic and orientation impacts were
respectively 82%, 47% and 85%. In 101 cases (44%), POCUS led to at least one
imaging change. The clinical value of POCUS, i.e. considering at least one impact
and/or imaging change, was assessed at 95%. CONCLUSION: This study shows that
POCUS is used on a minority of emergency patients. However, when used, it
significantly affects diagnostic and therapeutic practices in the emergency
setting.
PMID- 28412494
TI - Video-laryngoscopes for intubation in paediatrics: Is a better view makes
everything?
PMID- 28412495
TI - Epidemiology of Environmental Exposure and Malignant Mesothelioma.
AB - Although the association between exposure to asbestos and malignant mesothelioma
(particularly malignant pleural mesothelioma) has been well established, the
health impact of environmental exposure (EE) to asbestos has been less studied.
This review summarizes the most recent studies on the association between
malignant mesothelioma and EE with asbestos to identify features associated with
EE and quantify the association with malignant mesothelioma. There were 44
studies from 18 countries that met our selection criteria, with a considerable
amount of heterogeneity in their study design, measures of exposure, and health
outcomes. The male-to-female ratio was close to or less than 1 and generally
lower than the ratio reported when both occupational and environmental exposures
were considered. Although recent studies have continued to improve our
understanding of environmental exposure to asbestos, challenges remain. We have
highlighted a few new research directions, such as a need for reliable matrices
to identify common and less recognized types of EE, asbestos biomarker studies
specifically focusing on EE, and research on populations and geographic areas
that have not been previously studied.
PMID- 28412496
TI - Magnesium sulfate (MG) prevents maternal inflammation induced offspring cerebral
injury evident on MRI but not via IL-1beta.
AB - OBJECTIVE: As maternal treatment with magnesium sulfate (MG) may protect the
fetal brain, we sought to assess the inflammation associated neuroprotective
potential of MG and its association to interleukin 1beta (IL-1beta). METHODS:
Pregnant Sprague-Dawley rats at 18-day gestation received i.p. lipopolysaccharide
(LPS) or saline. Dams were randomized to treatment with s.c. saline (control), or
MG prior to or following the i.p. injection, resulting in three groups. At the
end of the treatment, fetal brain IL-1beta was quantified for 18 pregnant rats
(six of each group). Another 18 pregnant rats delivered spontaneously and pups
were allowed to mature. At postnatal day 25, female offspring were examined by
magnetic resonance imaging (MRI) and analyzed using voxel based analysis.
Apparent diffusion coefficient (ADC) and T2 relaxation protocols were performed
to assess white and gray matter injury. RESULTS: Offspring of LPS-treated dams
exhibited (1) significantly increased T2 levels, and (2) increased ADC levels in
white and gray matter, consistent with diffuse cerebral injury. Offspring of MG
treated LPS dams demonstrated similar T2 and ADC levels as control dams. Fetal
brain IL-1beta was significantly increased following maternal LPS compared to
control (0.125+/-0.01 vs 0.100+/-0.01u, p<0.05). No significant decrease in IL
1beta level was observed in response to maternal MG. CONCLUSIONS: Maternal LPS
induced neonatal brain injury can be prevented by maternal MG. Maternal MG
therapy may be effective in human deliveries associated with maternal/fetal
inflammation. The absence of a decrease in fetus brain levels of IL-1beta
following MG treatment implies that the mechanism of MG is not through inhibition
of IL-1beta production. SIGNIFICANCE STATEMENT: Intrauterine fetal exposure to
maternal inflammation and pro-inflammatory cytokines is associated with adverse
offspring neurological outcomes. Although its precise mechanism is not
elucidated, magnesium sulfate (MG) is commonly used as neuroprotection for white
matter brain injuries in preterm fetuses. A proposed mechanism involves the
ability of MG to reduce pro-inflammatory cytokine levels. In the current study,
we used a rat model of LPS-induced maternal inflammation to investigate the short
term effect of MG on fetal brain IL-1beta levels, and its long-term
neuroprotective effect on the offspring brain by using MRI. We demonstrated that
maternal administration of MG can prevent long-term neonatal brain injury but,
since no decrease was observed in fetal brain IL-1beta levels, the neuro
protective mechanism of MG is not mediated by inhibition of IL-1beta production.
PMID- 28412498
TI - Impact of thalamocortical input on barrel cortex development.
AB - The development of cortical maps requires the balanced interaction between
genetically determined programs and input/activity-dependent signals generated
spontaneously or triggered from the environment. The somatosensory pathway of
mice provides an excellent scenario to study cortical map development because of
its highly organized cytoarchitecture, known as the barrel field. This precise
organization makes evident even small alterations in the cortical map layout. In
this review, we will specially focus on the thalamic factors that control barrel
field development. We will summarize the role of thalamic input integration and
identity, neurotransmission and spontaneous activity in cortical map formation
and early cross-modal plasticity.
PMID- 28412497
TI - Optogenetic stimulation of cortex to map evoked whisker movements in awake head
restrained mice.
AB - Whisker movements are used by rodents to touch objects in order to extract
spatial and textural tactile information about their immediate surroundings. To
understand the mechanisms of such active sensorimotor processing it is important
to investigate whisker motor control. The activity of neurons in the neocortex
affects whisker movements, but many aspects of the organization of cortical
whisker motor control remain unknown. Here, we filmed whisker movements evoked by
sequential optogenetic stimulation of different locations across the left dorsal
sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked
by optogenetic stimulation of many regions in the dorsal sensorimotor cortex.
Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the
contralateral whisker after a short latency, and a delayed rhythmic protraction
of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked
rhythmic bilateral whisker protraction with a longer latency compared to
stimulation of sensory cortex. Compared to frontal cortex stimulation, larger
amplitude bilateral rhythmic whisking in a less protracted position was evoked at
a similar latency by stimulating a cortical region posterior to Bregma and close
to the midline. These data suggest that whisker motor control might be broadly
distributed across the dorsal mouse sensorimotor cortex. Future experiments must
investigate the complex neuronal circuits connecting specific cell-types in
various cortical regions with the whisker motor neurons located in the facial
nucleus.
PMID- 28412499
TI - Parkinsonism and dystonia are differentially induced by modulation of different
territories in the basal ganglia.
AB - Numerous clinical and experimental observations suggest that deficient neuronal
signaling in the globus pallidus externa (GPe) is integral to both Parkinson's
disease (PD) and dystonia. In our previous studies in jaundiced dystonic rats,
widespread silencing of neurons in GP (rodent equivalent to GPe) preceded and
persisted during dystonic motor activity. We therefore hypothesized that on a
background of slow and highly irregular and bursty neuronal activity in GP,
cortical motor drive produces profound inhibition of GP as the basis for action
induced dystonia in Gunn rats. Presently, the neurotoxin ibotenate was injected
locally into the motor territory of GP at one to four sites, over one to two
tracts, in 19 normal rats. We found that highly circumscribed dorsal motor
territory lesions reproducibly induced parkinsonism, while ventral lesions
consistently produced dystonia. Post-lesioning, slow neuronal burst oscillations
in the entopeduncular nucleus distinguished parkinsonian from dystonic rats.
Next, we compared the deep brain stimulation contact sites in the GP internus
used to treat patients with PD (n=21 implants in 12 successive patients) versus
dystonia (n=16 implants in nine patients) and found the efficacious territory for
ameliorating PD to be located chiefly dorsal to that for dystonia. The
comparative distribution for treating PD versus dystonia was therefore
anatomically consistent with that for inducing these features via GP lesions in
rodents. Our collective findings thus suggest that dystonia and parkinsonism are
differentially produced by pathological silencing of GPe neurons along distinct
motor sub-circuits, resulting in disparate pathological basal ganglia output
signaling.
PMID- 28412500
TI - The major neurotransmitter systems in the basolateral amygdala and the ventral
tegmental area mediate morphine-induced memory consolidation impairment.
AB - In the present study, we investigated the possible participation of the
endocannabinoid system in the basolateral amygdala and N-methyl-d-aspartate
(NMDA) or GABA-A receptor neurotransmission in the ventral tegmental area in the
memory consolidation impairment induced by morphine administration. To measure
memory formation, step-through type passive avoidance apparatus was used with
adult male Wistar rats. The results showed that intraperitoneal (i.p.)
administration of morphine (3 and 6mg/kg) after the successful training phase had
an amnestic effect and induced memory consolidation impairment. After training,
injection of a selective cannabinoid CB1 receptor agonist,
arachydonilcyclopropylamide (ACPA; 0.4-0.6ng/rat) plus systemic injection of an
ineffective dose of morphine (0.5mg/kg, i.p.) into the basolateral amygdala
impaired memory consolidation suggesting the facilitatory effect of ACPA on
morphine response. Also, the results showed that the injection of bicuculline, a
GABA-A receptor antagonist (0.3-0.5ug/rat) or NMDA (0.005-0.02ug/rat) into the
ventral tegmental area reversed ACPA-induced potentiation of morphine response
and improved memory consolidation. It should be considered that the injection of
ACPA into the basolateral amygdala and the injection of bicuculline or NMDA into
the ventral tegmental area alone could not affect memory consolidation. Taken
together, it seems that there is a functional interaction between the basolateral
amygdala endocannabinoid system and the ventral tegmental area GABAergic- or
glutamatergic neurotransmission in the modulation of morphine-induced memory
consolidation impairment.
PMID- 28412501
TI - Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in
response to cocaine.
AB - Chromatin regulation, in particular ATP-dependent chromatin remodelers, have
previously been shown to be important in the regulation of reward-related
behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A,
an accessory subunit of the ISWI family of chromatin remodeling complexes, is
downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to
cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in
mouse NAc reduces cocaine reward as assessed by conditioned place preference
(CPP), but increases cocaine-induced locomotor activation. Furthermore, we
investigate nucleosome repositioning genome-wide by conducting chromatin
immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and
after repeated cocaine administration, and find extensive nucleosome occupancy
and shift changes across the genome in response to cocaine exposure. These
findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and
offer new insight into the pathophysiology of cocaine addiction.
PMID- 28412502
TI - Enriched environment effects on remote object recognition memory.
AB - Since Ebbinghaus' classical work on oblivion and saving effects, we know that
declarative memories may become at first spontaneously irretrievable and only
subsequently completely extinguished. Recently, this time-dependent path toward
memory-trace loss has been shown to correlate with different patterns of brain
activation. Environmental enrichment (EE) enhances learning and memory and
affects system memory consolidation. However, there is no evidence on whether and
how EE could affect the time-dependent path toward oblivion. We used Object
Recognition Test (ORT) to assess in adult mice put in EE for 40days (EE mice) or
left in standard condition (SC mice) memory retrieval of the familiar objects 9
and 21days after learning with or without a brief retraining performed the day
before. We found that SC mice show preferential exploration of new object at day
9 only with retraining, while EE mice do it even without. At day 21 SC mice do
not show preferential exploration of novel object, irrespective of the
retraining, while EE mice are still capable to benefit from retraining, even if
they were not able to spontaneously recover the trace. Analysis of c-fos
expression 20days after learning shows a different pattern of active brain areas
in response to the retraining session in EE and SC mice, with SC mice recruiting
the same brain network as naive SC or EE mice following de novo learning. This
suggests that EE promotes formation of longer lasting object recognition memory,
allowing a longer time window during which saving is present.
PMID- 28412503
TI - Internet search volumes in brain aneurysms and subarachnoid hemorrhage: Is there
evidence of seasonality?
AB - OBJECTIVE: Results of previous studies examining seasonal variation in the
incidence of aneurysmal subarachnoid hemorrhage (SAH) are conflicting. The aim of
this brief report is to investigate whether there is a seasonal effect in online
search queries for SAH that may reflect an association between meteorological
factors and aneurysm rupture. PATIENTS AND METHODS: We used the Google Trends
data service to analyze the volume of internet queries for SAH on Google's search
engine from January 1, 2004 to November 2016. We used comprehensive search terms
and collected data from: USA, Canada, and countries known for their high
prevalence of SAH (Finland, and Japan), as well as worldwide search volume.
Potential seasonal variations in the data were assessed by comparative non
parametric tests and curve-fit regression model. RESULTS: Our analyses revealed
that USA had the highest median value in cumulative search scores (115 vs. 86,
46, 46 for Finland, Canada and Japan, respectively). The term "brain aneurysm"
was the commonly used search term among countries, followed by "cerebral
aneurysm". There was no evidence of seasonality in any of the countries studied
on both univariate tests and regression time-adjusted analysis. CONCLUSIONS:
There are no seasonal variations in internet search query volume for SAH. Further
studies are needed to explore whether online search volumes correlate with the
actual incidence of SAH.
PMID- 28412504
TI - Endotoxin induced TLR4 signaling downregulates CYP19A1 expression through CEBPB
in buffalo granulosa cells.
AB - Estrogen is essential for growth and development of ovarian follicles. Infections
associated with E. coli or Endotoxin (LPS) suppress estradiol production by the
downregulation of CYP19A1 expression. However, the molecular mechanism of its
down regulation is not yet known. To elucidate the molecular mechanisms of LPS
mediated downregulation of CYP19A1 gene expression, we studied the effect of LPS
and TLR4 signaling pathway inhibitor (OxPAPC, OxPAPC-Oxidized 1-palmitoyl-2
arachidonoyl-sn-glycero-3-phosphocholine) on CYP19A1 expression, and expression
of CEBPB and CEBPB binding on CYP19A1 proximal promoter (CYP19A1 PII) in buffalo
granulosa cells in vitro. The results showed that LPS (1MUg/ml) significantly
declined the expression of CYP19A1 gene. In further experiments, inhibitor
studies confirmed the involvement of TLR4 in LPS induced CYP19A1 gene down
regulation in buffalo granulosa cells. LPS promoted higher levels of CEBPB at
cellular and nuclear level in granulosa cells. Chromatin immunoprecipitation
results showed, that LPS induces higher amount of CEBPB binding on the CYP19A1
PII. Further, TLR4 inhibitor attenuated the LPS induced implications. In
conclusion, our results demonstrated that CEBPB could be a potential regulator
for LPS mediated downregulation of CYP19A1 and decline of 17-beta estradiol
levels in buffalo granulosa cells.
PMID- 28412505
TI - Various UVB doses affect change of raf kinase inhibitor protein, nitric oxide and
proliferation in keratinocytes.
AB - UVB is a potent modulator of cell growth and differentiation in the skin. The UVB
irradiation has been used in treating hyperproliferative dermatoses. Otherwise,
UVB radiation is also the major risk factor for developing skin cancer. Nitric
oxide (NO) has been suggested to be a physiological modulator of cell
proliferation. Raf-1 kinase inhibitory protein (RKIP) was involved in cell
growth, transformation, and differentiation. The purpose of this study was to
search for the possible cause of UVB-inhibited hyperplasia and UVB-resulted
hyperproliferation. We evaluated various UVB dose whether affect the expression
of RKIP, iNOS, NO and proliferation in keratinocyte. Normal human keratinocytes
were treated with UVB dose of 40mJ/cm2, 80mJ/cm2, 120mJ/cm2, 160mJ/cm2 and
0mJ/cm2 (control group) respectively. The results showed that RKIP, iNOS and NO
of keratinocytes with doses of 40mJ/cm2 and 80mJ/cm2 UVB treatment significantly
higher than control group (P<0.01). The proliferation of keratinocyte with doses
of 40mJ/cm2 and 80mJ/cm2 UVB treatment was significantly lower than control group
(P<0.01). However, RKIP, iNOS and NO of keratinocytes with doses of 120mJ/cm2 and
160mJ/cm2 UVB treatment significantly lower than control group (P<0.01). The
proliferation of keratinocyte with doses of 120mJ/cm2 and 160mJ/cm2 UVB treatment
was significantly higher than control group (P<0.01). In conclusion, these
results showed that the different UVB dosages induced various alteration of RKIP,
NO, iNOS and proliferation may provide important information on the therapeutic
molecular mechanism of UVB-inhibited hyperplasia and UVB resulted
hyperproliferation.
PMID- 28412506
TI - Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and
survival of HepG2 cells via activation of NFkappaB.
AB - Di (2-ethylhexyl)-phthalate (DEHP) is the most commonly used plasticizer. DEHP
can easily leach out from products into the environment and has become a
significant environmental contamination. However, its carcinogenic effects in
human remain controversial. In this study, we exposed hepatocellular carcinoma
HepG2 cells to different concentrations of DEHP for a period of times, followed
by a combination of RNA-seq analysis and molecular analysis for DEHP-altered
genes. We observed that long-term and very low-dose DEHP treatment has growth
inducing activity in HepG2 cells, while short-term and high-dose DEHP treatment
has little effects on tumor cell proliferation. Bioinformatic analysis further
revealed that a large subset of differentially expressed genes affected by DEHP
have functional annotations related to inflammation response. Importantly we
found that long-term DEHP treatment stimulated nuclear factor-kappa B (NF-kappa
B) activity in HepG2 cells, while inhibition of NFkappaB activity could offset
the effects of DEHP exposure. In conclusion, continuous DEHP treatment could
promote proliferation of HepG2 cells via activating NFkappaB signaling pathway.
PMID- 28412507
TI - Transcriptomic analyses of human bronchial epithelial cells BEAS-2B exposed to
atmospheric fine particulate matter PM2.5.
AB - Respiratory exposure is the major route of atmospheric PM2.5 entering the human
body. Epidemiological studies have indicated that exposure to PM2.5 is associated
with increased risk of pulmonary diseases, but the underlying mechanisms remain
less clear. In this study, human bronchial epithelial cells (BEAS-2B) were used
to investigate the toxic effect and gene expression changes induced by PM2.5
collected from Beijing, China, based on microarray and following bioinformatic
analyses. Gene ontology (GO) analysis indicated that PM2.5 caused significant
changes in gene expression patterns related to a series of important functions,
covering gene transcription, signal transduction, cell proliferation, cellular
metabolic processes, immune response, etc. Additionally, pathway analysis and
signal-net analysis showed that PI3K/Akt, MAPK, and TNF signaling pathways were
the most prominently significant pathways affected by PM2.5, which play key roles
in regulating cell proliferation, cell differentiation, cytoskeleton regulation,
and inflammatory response. Finally, for the purpose of verifing the accuracy of
microarray analysis, qRT-PCR was used to detect the expression of part key genes
in the above signaling pathways, which were selected from the signal-net. Our
study provided a large amount of information on the molecular mechanism that
underling PM2.5 caused pulmonary diseases, and follow-up researches are still
needed for further exploration.
PMID- 28412508
TI - Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24), a novel
tubulin inhibitor, causes G2/M arrest and cell apoptosis by disrupting tubulin
polymerization in human cervical and breast cancer cells.
AB - Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24) is a
newly synthesized analogue of nocodazole by our group and has been found to be
active for some cancer cells. However, its sensitivity to different cell lines
and the underlying anticancer mechanism are still unclear. In this study, we
proved that M-24 had strong time- and dose-dependent anti-proliferative effects
on human cervical cancer HeLa cells and human breast carcinoma MCF-7 cells. We
demonstrated that the growth inhibitory effects of M-24 in both cell lines were
associated with microtubule depolymerization. Furthermore, M-24 treatment
resulted in cell cycle arrest at the G2/M phase in a dose-dependent manner with
subsequent apoptosis induction. Western blotting analysis revealed that up
regulation of cyclin B1 and cdc2 was related with G2/M arrest in both cell lines.
In addition, M-24-induced HeLa cell apoptosis was mainly associated with
mitochondria-dependent intrinsic pathway. However, M-24-induced MCF-7 cell
apoptosis was associated with both mitochondrial and death receptor pathway. In
conclusion, M-24 caused apoptosis through disrupting microtubule assembly and
inducing cell cycle arrest in HeLa and MCF-7 cells. Therefore, the novel compound
M-24 is a promising microtubule-destabilizing agent that has great potential for
the therapy of various malignancies especially human cervical and breast cancers.
PMID- 28412509
TI - A monoclonal antibody recognizes undifferentiation-specific carbohydrate moieties
expressed on cell surface of the human dental pulp cells.
AB - Human dental pulp cells are obtained from dental pulp tissue, and have the
ability to form dentin and a pulp-like complex. Although adult stem cells have
been identified from the primary culture by using specific cell surface markers,
the identity of surface markers for the purification of stem cells within the
dental pulp population are still unclear. Previously, we had constructed
monoclonal antibodies against the undifferentiated cell-specific surface markers
of human dental pulp cells (hDPCs) by performing decoy immunization. Among them,
a monoclonal antibody against the cell surface antigen of the undifferentiated
hDPCs (named UPSA-1) was purified and its heavy and light chain consensus regions
were analyzed. The cell surface binding affinity of UPSA-1 mAb on the
undifferentiated hDPCs was stronger than that on the differentiated cells. When
tunicamycin was applied to hDPSCs during culture, the cell surface binding
affinity of the antibody was dramatically decreased, and dentinogenic
differentiation was reduced. The purified UPSA-1 antigen band resulting from
immunoprecipitation disappeared or shifted down on the SDS-PAGE by
deglycosylation. These data suggested that glycosylation on the cell surface
might be a marker of an undifferentiated state, and that UPSA-1 mAb might be
useful for identifying the carbohydrate moiety on the cell surface of
undifferentiated pulp cells.
PMID- 28412510
TI - Empathy networks in the parental brain and their long-term effects on children's
stress reactivity and behavior adaptation.
AB - Parental empathy is a key component of sensitive parenting that supports
children's social adaptation throughout life. Consistent with a two dissociable
network perspective on empathy, we measured within- and between-network integrity
of two empathy-related networks in the parental brain as predictors of children's
social outcomes across the first six years of life. We focused on two empathy
networks; embodied simulation, which supports parents' capacity to resonate with
infant state and emotions and implicates cingulo-insulary structures, and
mentalizing, which underpins parents' theory-of-mind and mental attributions via
prefrontal-temporo-parietal circuit. We followed 87 first-time parents across the
first six years of family formation, including heterosexual and homosexual
parents. In infancy, parents' brain response to own versus unfamiliar infant
stimuli was imaged; in preschool, children's cortisol production and emotion
regulation were assessed; and at six years, children's behavior problems were
reported. Parents' intra- and inter- network integrity increased when viewing
their own infant compared to unfamiliar infant, suggesting that attachment
stimuli increase network coherence in the parental brain. Functional connectivity
within the parent's embodied simulation network in infancy predicted lower child
cortisol production while inter-network connectivity among the embodied
simulation and mentalizing networks was associated with more advanced child
emotion regulation skills in preschool and lower internalizing problems at six
years. Children's emotion regulation capacities mediated the link between inter
network integrity in the parental brain and internalizing symptoms. Our findings,
the first to demonstrate that integrity of empathy-related networks in the
parental brain shape children's long-term stress reactivity and emotional
adaptation, highlight the brain component of the parental empathy attribute,
suggest that increased coherence within the "parental caregiving network" marks a
key feature of parent-infant attachment, and contribute to discussion on
biobehavioral mechanisms underpinning the cross-generation transmission of human
stress reactivity and sociality.
PMID- 28412511
TI - Difference in neural response to social exclusion observation and subsequent
altruism between adolescents and adults.
AB - Empathy and prosocial behaviors toward peers promote successful social
development and creation of significant long-term relationships, but surprisingly
little is known about the maturation of these skills during the period of
adolescence. As the majority of studies have used questionnaires or pain
observation paradigms, it remains unknown whether the empathic response of
adolescents differs from that of adults in a paradigm that is closer to everyday
life. In the current study, fMRI was used to examine the neural correlates of
social exclusion observation and subsequent prosocial behavior in 20 adolescents
(aged 12-17 years) and 20 adults (aged 22-30 years) while playing a ball-tossing
game with what they believed to be real individuals. Observing someone being
excluded compared to observing equal inclusion of all players elicited a
significantly higher activation of the IFG (pars triangularis) in adults compared
to adolescents. When given the opportunity to directly help the excluded player
during the game, adolescents showed significantly less prosocial behavior than
adults, which was underpinned by a significantly lower activity in the right
temporoparietal junction, medial/dorsomedial prefrontal cortex and fusiform face
area. These findings might indicate that adolescents have a lower propensity to
take the victim's perspective and share his or her distress when witnessing
social exclusion, which leads to a lower altruistic motivation to help. The
factors that could generate what can be interpreted as a downward modulation of
empathy during adolescence are discussed.
PMID- 28412513
TI - Wolbachia-induced loss of male fertility is likely related to branch chain amino
acid biosynthesis and iLvE in Laodelphax striatellus.
AB - Wolbachia are endosymbionts that infect many species of arthropods and nematodes.
Wolbachia-induced cytoplasmic incompatibility (CI) is the most common phenotype
in affected hosts, involving embryonic lethality in crosses between Wolbachia
infected males and uninfected females. The molecular mechanisms underlying this
phenomenon are currently unclear. Here we examine the molecular correlates of the
Wolbachia infection in Laodelphax striatellus (Fallen), an important rice pest,
where embryonic lethality is strong and almost complete. We compared the gene
expression of 4-day-old Wolbachia-infected and uninfected L. striatellus testes
to identify candidate genes for paternal-effect embryonic lethality induction.
Based on microarray analysis, iLvE was the most down-regulated gene; this gene
mediates branched-chain amino acid (BCAA) biosynthesis and participates in many
processes related to reproductive performance. After knocking down iLvE by RNAi
in uninfected male L. striatellus, male fertility was reduced, leading to a
decrease in embryo hatching rates, but fertility was rescued in crosses between
these males and Wolbachia-infected females. Removal of BCAA in chemically-defined
diets of uninfected males also led to a loss of male fertility. Low amino acid
nutrition may enhance exposure time of sperm to Wolbachia in the testes to affect
adult reproduction in L. striatellus by reducing the number of sperm transferred
per mating by males. These results indicate that Wolbachia may decrease male
fertility in L. striatellus by acting on iLvE, a key factor of BCAA biosynthesis,
and delaying sperm maturation.
PMID- 28412512
TI - Addressing the selective role of distinct prefrontal areas in response
suppression: A study with brain tumor patients.
AB - The diverging evidence for functional localization of response inhibition within
the prefrontal cortex might be justified by the still unclear involvement of
other intrinsically related cognitive processes like response selection and
sustained attention. In this study, the main aim was to understand whether
inhibitory impairments, previously found in patients with both left and right
frontal lesions, could be better accounted for by assessing these potentially
related cognitive processes. We tested 37 brain tumor patients with left
prefrontal, right prefrontal and non-prefrontal lesions and a healthy control
group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory
impairments are likely to cause false alarms, although additionally the former
task requires response selection and the latter target detection abilities.
Irrespective of the task context, patients with right prefrontal damage showed
frequent Go and target omissions, probably due to sustained attention lapses.
Left prefrontal patients, on the other hand, showed both Go and target omissions
and high false alarm rates to No-Go and warning stimuli, suggesting a decisional
rather than an inhibitory impairment. An exploratory whole-brain voxel-based
lesion-symptom mapping analysis confirmed the association of left ventrolateral
and dorsolateral prefrontal lesions with target discrimination failure, and right
ventrolateral and medial prefrontal lesions with target detection failure.
Results from this study show how left and right prefrontal areas, which previous
research has linked to response inhibition, underlie broader cognitive control
processes, particularly involved in response selection and target detection.
Based on these findings, we suggest that successful inhibitory control relies on
more than one functionally distinct process which, if assessed appropriately,
might help us to better understand inhibitory impairments across different
pathologies.
PMID- 28412514
TI - Insights from the genome of a high alkaline cellulase producing Aspergillus
fumigatus strain obtained from Peruvian Amazon rainforest.
AB - Here, we report the complete genome sequence of a high alkaline cellulase
producing Aspergillus fumigatus strain LMB-35Aa isolated from soil of Peruvian
Amazon rainforest. The genome is ~27.5mb in size, comprises of 228 scaffolds with
an average GC content of 50%, and is predicted to contain a total of 8660 protein
coding genes. Of which, 6156 are with known function; it codes for 607 putative
CAZymes families potentially involved in carbohydrate metabolism. Several
important cellulose degrading genes, such as endoglucanase A, endoglucanase B,
endoglucanase D and beta-glucosidase, are also identified. The genome of A.
fumigatus strain LMB-35Aa represents the first whole sequenced genome of non
clinical, high cellulase producing A. fumigatus strain isolated from forest soil.
PMID- 28412515
TI - Genome-wide determination of transcription start sites reveals new insights into
promoter structures in the actinomycete Corynebacterium glutamicum.
AB - The genome-wide identification of transcription start sites, enabled by high
throughput sequencing of a cDNA library enriched for native 5' transcript ends,
is ideally suited for the analysis of promoters. Here, the transcriptome of
Corynebacterium glutamicum, a non-pathogenic soil bacterium from the
actinomycetes branch that is used in industry for the production of amino acids,
was analysed by transcriptome sequencing of the 5'-ends of native transcripts.
Total RNA samples were harvested from the exponential phase of growth, therefore
the study mainly addressed promoters recognized by the main house-keeping sigma
factor sigmaA. The identification of 2454 transcription start sites (TSS) allowed
the detailed analysis of most promoters recognized by sigmaA and furthermore
enabled us to form different promoter groups according to their location relative
to protein-coding regions. These groups included leaderless transcripts (546
promoters), short-leadered (<500 bases) transcripts (917), and long-leadered
(>500 bases) transcripts (173) as well as intragenic (557) and antisense
transcripts (261). All promoters and the individual groups were searched for
information, e.g. conserved residues and promoter motifs, and general design
features as well as group-specific preferences were identified. A purine was
found highly favored as TSS, whereas the -1 position was dominated by
pyrimidines. The spacer between TSS and -10 region were consistently 6-7 bases
and the -10 promoter motif was generally visible, whereas a recognizable -35
region was only occurring in a smaller fraction of promoters (7.5%) and enriched
for leadered and antisense transcripts but depleted for leaderless transcripts.
Promoters showing an extended -10 region were especially frequent in case of non
canonical -10 motifs (45.5%). Two bases downstream of the -10 core region, a G
was conserved, exceeding 40% abundance in most groups. This fraction reached
74.6% for a group of putative sigmaB-dependent promoters, thus giving a hint to a
specific property of these promoters. In addition, the high number of promoters
analysed allowed finding of subtle signals only showing up significantly with
this large set. This included the observation of a periodically changing A+T
content with maxima spaced by a full turn of the DNA helix. This periodic
structure includes the A+T-rich UP-element of bacterial promoters known before
but was found to extend up to -100, indicating hitherto unknown constraints
influencing promoter architecture and possibly also promoter function.
PMID- 28412516
TI - Switching between nitrogen and glucose limitation: Unraveling transcriptional
dynamics in Escherichia coli.
AB - Transcriptional control under nitrogen and carbon-limitation conditions have been
well analyzed for Escherichia coli. However, the transcriptional dynamics that
underlie the shift in regulatory programs from nitrogen to carbon limitation is
not well studied. In the present study, cells were cultivated at steady state
under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose)
limitation to monitor changes in transcriptional dynamics. Nitrogen limitation
was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the
"housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under
glucose limitation. During the transition, nitrogen-mediated control was rapidly
redeemed and mRNAs that encode active uptake systems, such as ptsG and manXYZ,
were quickly amplified. Next, genes encoding facilitators such as lamB were
overexpressed, followed by high affinity uptake systems such as mglABC and non
specific porins such as ompF. These regulatory programs are complex and require
well-equilibrated and superior control. At the metabolome level, 2-oxoglutarate
is the likely component that links carbon- and nitrogen-mediated regulation by
interacting with major regulatory elements. In the case of dual glucose and
ammonia limitation, sigma 24 (RpoE) appears to play a key role in orchestrating
these complex regulatory networks.
PMID- 28412517
TI - Challenges around Access to and Cost of Life-Saving Medications after Allogeneic
Hematopoietic Cell Transplantation for Medicare Patients.
AB - Hematopoietic cell transplantation (HCT) is an expensive, medically complicated,
and potentially life-threatening therapy for multiple hematologic and
nonhematologic disorders with a prolonged trajectory of recovery. Similar to
financial issues in other cancer treatments, adverse financial consequences of
HCT are emerging as an important issue and may be associated with poor quality of
life and increased distress in HCT survivors. Prescription medicine coverage for
HCT for Medicare and some Medicaid beneficiaries, especially in the long-term,
remains suboptimal because of inadequate payer formularies or prohibitive copays.
With an increasing number of older patients undergoing HCT and improvement in the
overall survival after HCT, the problem of financial burden faced by Medicare
beneficiaries with fixed incomes is going to worsen. In this article, we describe
the typical financial burden borne by HCT recipients based on estimated copayment
amounts attached to the categories of key medications as elucidated through 2
case studies. We also suggest some possible solutions for consideration to help
these patients and families get through the HCT by minimizing the financial
burden from essential medications needed during the post-HCT period.
PMID- 28412519
TI - Vitamin D signaling in intestinal innate immunity and homeostasis.
AB - The lumen of the gut hosts a plethora of microorganisms that participate in food
assimilation, inactivation of harmful particles and in vitamin synthesis. On the
other hand, enteric flora, a number of food antigens, and toxins are capable of
triggering immune responses causing inflammation, which, when unresolved, may
lead to chronic conditions such as inflammatory bowel disease (IBD). It is
important, therefore, to contain the gut bacteria within the lumen, control
microbial load and composition, as well as ensure adequate innate and adaptive
immune responses to pathogenic threats. There is growing evidence that vitamin D
signaling has impacts on all these aspects of intestinal physiology, contributing
to healthy enteric homeostasis. VD was first discovered as the curative agent for
nutritional rickets, and its classical actions are associated with calcium
absorption and bone health. However, vitamin D exhibits a number of extra
skeletal effects, particularly in innate immunity. Notably, it stimulates
production of pattern recognition receptors, anti-microbial peptides, and
cytokines, which are at the forefront of innate immune responses. They play a
role in sensing the microbiota, in preventing excessive bacterial overgrowth, and
complement the actions of vitamin D signaling in enhancing intestinal barrier
function. Vitamin D also favours tolerogenic rather than inflammogenic T cell
differentiation and function. Compromised innate immune function and overactive
adaptive immunity, as well as defective intestinal barrier function, have been
associated with IBD. Importantly, observational and intervention studies support
a beneficial role of vitamin D supplementation in patients with Crohn's disease,
a form of IBD. This review summarizes the effects of vitamin D signaling on
barrier integrity and innate and adaptive immunity in the gut, as well as on
microbial load and composition. Collectively, studies to date reveal that vitamin
D signaling has widespread effects on gut homeostasis, and provide a mechanistic
basis for potential therapeutic benefit of vitamin D supplementation in IBD.
PMID- 28412518
TI - Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease
Prophylaxis after Allogeneic Transplantation.
AB - Atorvastatin administration to both the donors and recipients of matched related
donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute
graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and
effective. However, its efficacy as acute GVHD prophylaxis when given only to
allo-HCT recipients is unknown. We conducted a phase II study to evaluate the
safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to
the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo
HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered
along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate.
All patients were evaluable for acute GVHD. The cumulative incidences of grade II
to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence
interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The
cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and
MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%),
respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year
were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively.
In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression
free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95%
CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to
83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95%
CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%),
and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities
attributable to atorvastatin were seen. In conclusion, the addition of
atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD
allo-HCT appears to be feasible and safe. The preliminary efficacy seen here
warrants confirmation in randomized trials.
PMID- 28412520
TI - Nutrition modulation of human aging: The calorie restriction paradigm.
AB - Globally, the aging population is growing rapidly, creating an urgent need to
attenuate age-related health conditions, including metabolic disease and
disability. A promising strategy for healthy aging based on consistently positive
results from studies with a variety of species, including non-human primates
(NHP), is calorie restriction (CR), or the restriction of energy intake while
maintaining intake of essential nutrients. The burgeoning evidence for this
approach in humans is reviewed and the major study to date to address this
question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing
Intake of Energy), is described. CALERIE findings indicate the feasibility of CR
in non-obese humans, confirm observations in NHP, and are consistent with
improvements in disease risk reduction and potential anti-aging effects. Finally,
the mechanisms of CR in humans are reviewed which sums up the fact that
evolutionarily conserved mechanisms mediate the anti-aging effects of CR.
Overall, the prospect for further research in both NHP and humans is highly
encouraging.
PMID- 28412521
TI - A lamprey view on the origins of neuroendocrine regulation of the thyroid axis.
AB - This mini review summarizes the current knowledge of the hypothalamic-pituitary
thyroid (HPT) endocrine system in lampreys, jawless vertebrates. Lampreys and
hagfish are the only two extant members of the class of agnathans, the oldest
lineage of vertebrates. The high conservation of the hypothalamic-pituitary
gonadal (HPG) axis in lampreys makes the lamprey model highly appropriate for
comparative and evolutionary analyses. However, there are still many unknown
questions concerning the hypothalamic-pituitary (HP) axis in its regulation of
thyroid activities in lampreys. As an example, the hypothalamic and pituitary
hormone(s) that regulate the HPT axis have not been confirmed and/or
characterized. Similar to gnathostomes (jawed vertebrates), lampreys produce
thyroxine (T4) and triiodothyronine (T3) from thyroid follicles that are
suggested to be involved in larval development, metamorphosis, and reproduction.
The existing data provide evidence of a primitive, overlapping yet functional HPG
and HPT endocrine system in lamprey. We hypothesize that lampreys are in an
evolutionary intermediate stage of hypothalamic-pituitary development, leading to
the emergence of the highly specialized HPG and HPT endocrine axes in jawed
vertebrates. Study of the ancient lineage of jawless vertebrates, the agnathans,
is key to understanding the origins of the neuroendocrine system in vertebrates.
PMID- 28412522
TI - Small non coding RNAs in adipocyte biology and obesity.
AB - Obesity has reached epidemic proportions world-wide and constitutes a substantial
risk factor for hypertension, type 2 diabetes, cardiovascular diseases and
certain cancers. So far, regulation of energy intake by dietary and
pharmacological treatments has met limited success. The main interest of current
research is focused on understanding the role of different pathways involved in
adipose tissue function and modulation of its mass. Whole-genome sequencing
studies revealed that the majority of the human genome is transcribed, with
thousands of non-protein-coding RNAs (ncRNA), which comprise small and long
ncRNAs. ncRNAs regulate gene expression at the transcriptional and post
transcriptional level. Numerous studies described the involvement of ncRNAs in
the pathogenesis of many diseases including obesity and associated metabolic
disorders. ncRNAs represent potential diagnostic biomarkers and promising
therapeutic targets. In this review, we focused on small ncRNAs involved in the
formation and function of adipocytes and obesity.
PMID- 28412523
TI - Progenitor strain introduction of Mycobacterium bovis at the wildlife-livestock
interface can lead to clonal expansion of the disease in a single ecosystem.
AB - Mycobacterium bovis infects multiple wildlife species and domesticated cattle
across South Africa, and negatively impacts on livestock trade and movement of
wildlife for conservation purposes. M. bovis infection was first reported in the
Kruger National Park (KNP) in South Africa during the 1990s, and has since spread
to infect numerous animal host species throughout the park and across South
Africa. Whole genome sequencing data of 17 M. bovis isolates were analyzed to
investigate the genomic diversity among M. bovis isolates causing disease in
different animal host species from various locations in South Africa. M. bovis
strains analyzed in this study are geographic rather than host species-specific.
The clonal expansion of M. bovis in the KNP highlights the effect of an
introduction of a transmissible infectious disease leading to a rising epidemic
in wildlife, and emphasizes the importance of disease control and movement
restriction of species that serve as disease reservoirs. In conclusion, the point
source introduction of a single M. bovis strain type in the KNP ecosystem lead to
an M. bovis outbreak in this area that affects various host species and poses an
infection risk in neighboring rural communities where HIV prevalence is high.
PMID- 28412524
TI - Antimicrobial resistance and genetic diversity of the SXT element in Vibrio
cholerae from clinical and environmental water samples in northeastern Thailand.
AB - Multidrug resistance in V. cholerae has been increasing around the world
including northeastern Thailand. The aquatic environment is a reservoir of V.
cholerae and might be an important source of resistant strains. The aims of this
study were to investigate the phylogenetic relationships of intSXT gene sequences
from 31 clinical and 14 environmental V. cholerae O1 and non-O1/non-O139 isolates
and 11 sequences amplified directly from environmental water samples. We also
amplified class 1 integrons, the SXT elements (targeting the intSXT gene) and
antimicrobial resistance genes directly from water samples. Phylogenetic analysis
displayed two major distinct clusters (clusters 1 and 2). Most V. cholerae O1
(19/20, 95%) and non-O1/non-O139 isolates (8/11, 72.7%) from clinical sources,
and all sequences obtained directly from water samples, belonged to cluster 1.
Cluster 2 mostly comprised environmental non-O1/non-O139 isolates (10/12, 83.3%).
We successfully amplified the SXT elements directly from17.5% of water samples.
Associated resistance genes were also amplified as follows: sul2 (41.3% of water
samples), dfrA1 (60%), dfr18 (33.8%), strB (70%) and tetA (2.5%). Class 1
integrons were not found in water samples, indicating that the SXT element was
the major contributor of multidrug resistance determinants in this region. The
SXT element and antimicrobial resistance genes could be transferred from clinical
V. cholerae O1 to environmental V. cholerae non-O1/non-O139 was demonstrated by
conjugation experiment. These findings indicate that there may have been cross
dissemination and horizontal gene transfer (HGT) of the SXT element harbored by
V. cholerae O1 and non-O1/non-O139 strains isolated from clinical and
environmental water sources. Environmental water might be an important source of
antimicrobial resistance genes in V. cholerae in this region. Direct detection of
antimicrobial resistance genes in water samples can be used for monitoring the
spread of such genes in the ecosystem.
PMID- 28412525
TI - Liver microbiome of Peromyscus leucopus, a key reservoir host species for
emerging infectious diseases in North America.
AB - Microbiome studies generally focus on the gut microbiome, which is composed of a
large proportion of commensal bacteria. Here we propose a first analysis of the
liver microbiome using next generation sequencing as a tool to detect potentially
pathogenic strains. We used Peromyscus leucopus, the main reservoir host species
of Lyme disease in eastern North America, as a model and sequenced V5-V6 regions
of the 16S gene from 18 populations in southern Quebec (Canada). The
Lactobacillus genus was found to dominate the liver microbiome. We also detected
a large proportion of individuals infected by Bartonella vinsonii arupensis, a
human pathogenic bacteria responsible for endocarditis, as well as Borrelia
burgdorferi, the pathogen responsible for Lyme disease in North America. We then
compared the microbiomes among two P. leucopus genetic clusters occurring on
either side of the St. Lawrence River, and did not detect any effect of the host
genotype on their liver microbiome assemblage. Finally, we report, for the first
time, the presence of B. burgdorferi in a small mammal host from the northern
side of the St. Lawrence River, in support of models that have predicted the
northern spread of Lyme disease in Canada.
PMID- 28412526
TI - Birth setting, labour experience, and postpartum psychological distress.
AB - OBJECTIVE: although psychosocial risk factors have been identified for postpartum
depression (PPD) and perinatal posttraumatic stress disorder (PTSD), the role of
labour- and birth-related factors remains unclear. The present investigation
explored the impact of birth setting, subjective childbirth experience, and their
interplay, on PPD and postpartum PTSD. METHOD: in this prospective longitudinal
cohort study, three groups of women who had vaginal births at a tertiary care
hospital, a birthing center, and those transferred from the birthing centre to
the tertiary care hospital were compared. Participants were followed twice during
pregnancy (12-14 and 32-34 weeks gestation) and twice after childbirth (1-3 and 7
9 weeks postpartum). RESULTS: symptoms of PPD and PTSD did not significantly
differ between birth groups; however, measures of subjective childbirth
experience and obstetric factors did. Moderation analyses indicated a significant
interaction between pain and birth group, such that higher ratings of pain among
women who were transferred was associated with greater symptoms of postpartum
PTSD. CONCLUSION AND IMPLICATIONS FOR PRACTICE: women who are transferred appear
to have a unique experience that may put them at greater risk for postpartum
psychological distress. It may be beneficial for care providers to help prepare
women for pain management and potential unexpected complications, particularly if
it is their first childbirth.
PMID- 28412527
TI - Aquaporins as potential drought tolerance inducing proteins: Towards instigating
stress tolerance.
AB - Aquaporins (AQPs) are primarily involved in maintaining cellular water
homeostasis. Their role in diverse physiological processes has fascinated plant
scientists for more than a decade, particularly concerning abiotic stresses.
Increasing examples of evidence in various crop plants indicate that the AQPs are
responsible for precise regulation of water movement and consequently play a
crucial role in the drought stress tolerance. Since drought is one of the major
abiotic stresses affecting agricultural production worldwide, it has become a
critical agenda to focus research on the development of drought tolerant crop
plants. AQPs can act as key candidate molecules to confront this issue. Hence,
there is an important need to explore the potential of AQPs by understanding the
molecular mechanisms and pathways through which they induce drought tolerance.
Moreover, the signalling network/s involved in such pathways needs to be mined
and understood correctly, and that may lead to the development of drought
tolerance in crop plants. In the present review, opportunity and challenges
regarding the efficient utilization of AQP-related information is presented and
discussed. The complied information and the discussion will be helpful for
designing future experiments and to set the specific goals for the enhancement of
drought tolerance in crop plants. Biological Significance Knowledge on the role
of AQPs in maintaining cellular water homeostasis has given new hope for
developing drought tolerance in crop plants. Since drought is one of the major
abiotic stresses affecting agricultural production worldwide, it has become a
critical agenda to focus research on the development of drought-tolerant crop
plants. AQPs can act as key candidate molecules to solve this problem through
genetic engineering. For this, it is important to understand the molecular
mechanisms and inter-related pathways through which AQPs induce drought tolerance
and to explore the signaling network/s involved in such pathways.
PMID- 28412528
TI - The global strategy employed by Xanthomonas oryzae pv. oryzae to conquer low
oxygen tension.
AB - : Xanthomonas oryzae pv. oryzae (Xoo) is a notorious rice pathogen that causes
bacterial leaf blight (BLB), a destructive rice disease. Low-oxygen tension in
the xylem vessels of rice stresses Xoo during infection. In this study,
differentially expressed proteins under normoxic and hypoxic conditions were
identified using high-performance liquid chromatography (HPLC) coupled with LC
MS/MS to investigate the global effects of low oxygen environment on Xoo PXO99A.
A statistically validated list of 187 (normoxia) and 140 (hypoxia) proteins with
functional assignments was generated, allowing the reconstruction of central
metabolic pathways. Ten proteins involved in aromatic amino acid biosynthesis,
glycolysis, butanoate metabolism, propanoate metabolism and biological adhesion
were significantly modulated under low-oxygen tension. The genes encoded by these
proteins were in-frame deleted, and three of them were determined to be required
for full virulence in Xoo. The contributions of these three genes to important
virulence-associated functions, including extracellular polysaccharide, cell
motility and antioxidative ability, are presented. BIOLOGICAL SIGNIFICANCE: To
study how Xanthomonas oryzae pv. oryzae (Xoo) conquers low-oxygen tension in the
xylem of rice, we identified differentially expressed proteins under normoxic and
hypoxia. We found 140 proteins that uniquely expressed under the hypoxia were
involved in 33 metabolism pathways. We identified 3 proteins were required for
full virulence in Xoo and related to the ability of extracellular polysaccharide,
cell motility, and antioxidative. This study is helpful for broadening our
knowledge of the metabolism processed of Xoo in the xylem of rice.
PMID- 28412529
TI - Vertical string-pulling in green jays (Cyanocorax yncas).
AB - The cognition of green jays (Cyanocorax yncas), a non Corvus corvid species, was
investigated by using the string-pulling paradigm. Five adult green jays
performed a vertical string-pulling task in which they had to retrieve a worm
attached to the end of a vertical hanging string while sitting on their perch. In
the first experiment, three of the subjects managed to retrieve the worm by
pulling on the string with their beaks and stepping on the resulting loop, and
thereafter repeating this sequence until the worm was accessible. When subjects
were given a choice between two strings in subsequent experiments 2-4, they chose
at random between the string connected to the worm and the one connected to a
slice of a wooden dowel. In experiment 5, subjects that had failed the previous
discrimination series were able, nevertheless, to solve a more stringent vertical
string array in which they had to pull up the whole length of the string without
any visual access to the worm at the end. We discuss green jays' performance in
comparison with other corvid species in which cognition has been more extensively
investigated.
PMID- 28412530
TI - Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.
AB - Indoles constitute extensively explored heterocyclic ring systems with wide range
of applications in pathophysiological conditions that is, cancer, microbial and
viral infections, inflammation, depression, migraine, emesis, hypertension, etc.
Presence of indole nucleus in amino acid tryptophan makes it prominent in
phytoconstituents such as perfumes, neurotransmitters, auxins (plant hormones),
indole alkaloids etc. The interesting molecular architecture of indole makes them
suitable candidates for the drug development. This review article provides an
overview of the chemistry, biology, and toxicology of indoles focusing on their
application as drugs. Our effort is to corroborate the information available on
the natural indole alkaloids, indole based FDA approved drugs and clinical trial
candidates having diverse therapeutic implementations. This compiled information
may serve as a benchmark for the alteration of existing ligands to design novel
potent molecules with lesser side effects.
PMID- 28412531
TI - Vagus nerve is involved in the changes in body temperature induced by
intragastric administration of 1,8-cineole via TRPM8 in mice.
AB - Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by
mild cold temperature (<28 degrees C). TRPM8 expressed in cutaneous sensory
nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected
in various tissues, including the gastrointestinal mucosa, and in the vagal
afferent nerve. The relationship between vagal afferent nerve-specific expression
of TRPM8 and thermoregulation remains unclear. In this study, we aimed to
investigate whether TRPM8 expression in the vagal afferent nerve is involved in
autonomic thermoregulation. We found that intragastric administration of 1,8
cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and
colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these
responses. Intravenous administration of 1,8-cineole also showed similar effects.
In vagotomized mice, the responses induced by intragastric administration of 1,8
cineole were attenuated. These results suggest that TRPM8 expressed in tissues
apart from cutaneous sensory nerves are involved in autonomic thermoregulation
response.
PMID- 28412532
TI - Spectral analysis highlight developmental EEG changes in preterm infants without
overt brain damage.
AB - Early markers of neurological outcome in the absence of overt brain damage are
scarce in extreme prematurity. The aim of this study was to compare spectral EEG
values of infants born near term with those of infants born at extremely low
gestational age (ELGA) but having attained near term age. We aimed also to
evaluate whether spectral EEG features were related with neurological outcome.
The ELGA group consisted of 12 neonates born between 23+2 and 27+6 weeks; the
control group consisted of nine infants born 34-35+2 weeks, tested within the
first week of life. All neonates underwent multichannel EEG recordings at 35
weeks post-conception. None of the subjects had apparent neurological
abnormalities or risk factors at the time of recording. EEG data were transformed
into the frequency domain and divided into delta (0.5-4Hz), theta (5-7Hz), alpha
(8-13Hz), beta (14-20Hz) frequency bands; relative EEG power values were
calculated. ELGA group was compared with the control group using a mixed analysis
of variance. Outcome was evaluated at one year of age by Griffiths' scales. A
principal effect of frequency and an interaction effect of frequency * group was
found. The total relative power of the delta band was significantly higher in
ELGA than in control group, whereas in the remaining frequency bands total
relative power was lower in ELGA than in control group. Higher values of delta
and lower values of alpha and beta spectral power correlated with poor outcome.
We provide preliminary results suggesting that, as early as 35 weeks post
conception, infants born extremely preterm fail to develop the age specific
pattern of EEG spectral activity, in the absence of neurological neonatal risk.
PMID- 28412533
TI - Print-specific N170 involves multiple subcomponents for Japanese Hiragana.
AB - Print-specific N170 in event-related potentials is generally considered to
reflect relatively automatic processing for letter strings, which is crucial for
fluent reading. However, our previous studies demonstrated that print-specific
N170 for transparent Japanese Hiragana script consists of at least two
subcomponents under rapid stimulus presentation: an attention-related left
lateralized N170 and a bilateral N170 associated with more automatic orthographic
processes (Okumura, Kasai & Murohashi, 2014, 2015). The present study aimed to
confirm the latter component by controlling presentation frequency of letters and
nonlinguistic visual controls (i.e., symbols), but found a quite different
pattern of results; an enhanced occipito-temporal positivity for words (80-120ms
poststimulus) followed by the typical left-lateralized N170 and an enhanced
parietal negativity for nonwords (150-200ms). These results should provide
further insights into the interaction processes between attention and early
stages of print processing.
PMID- 28412535
TI - Complex biogeographic scenarios revealed in the diversification of the largest
woodpecker radiation in the New World.
AB - Phylogenetic relationships and patterns of evolution within Melanerpes, one of
the most diverse groups of New World woodpeckers (22-23 lineages), have been
complicated due to complex plumages and morphological adaptations. In an attempt
to resolve these issues, we obtained sequence data from four nuclear introns and
two mitochondrial protein-coding genes for 22 of the 24 currently recognized
species in the genus. We performed phylogenetic analyses involving Maximum
Likelihood and Bayesian Inference, species-tree divergence dating, and
biogeographic reconstructions. Tree topologies from the concatenated and species
tree analyses of the mtDNA and nDNA showed broadly similar patterns, with three
relatively well-supported groups apparent: (a) the Sphyrapicus clade (four
species); (b) the typical Melanerpes clade, which includes temperate and
subtropical dry forest black-backed species; and (c) the mostly barred-backed
species, here referred to as the "Centurus" clade. The phylogenetic position of
Melanerpes superciliaris regarding the rest of Melanerpes is ambiguous as it is
recovered as sister to the rest of Melanerpes or as sister to a group including
Sphyrapicus+Melanerpes. Our species tree estimations recovered the same well
delimited highly-supported clades. Geographic range evolution (estimated in
BioGeoBEARS) was best explained by a DIVALIKE+j model, which includes vicariance,
founder effect speciation, and anagenetic dispersal (range expansion) as
important processes involved in the diversification of the largest radiation of
woodpeckers in the New World.
PMID- 28412534
TI - Isolation and identification of culturable bacteria, capable of heterotrophic
growth, from rapid sand filters of drinking water treatment plants.
AB - The microbial community in sand filters (SFs) of drinking water treatment plants
(DWTPs) likely contributes to SF functionalities, such as organic carbon removal
through heterotrophic metabolism. However, the dynamics and functionality of the
SF microbiome and microbial communities in oligotrophic freshwater environments
in general, are poorly understood. Therefore, the availability of bacterial
strains from these oligotrophic environments is of great interest, but such
organisms are currently underrepresented in culture collections. Focusing on
heterotrophic carbon metabolism, bacteria were isolated from SFs using
conventional media and media that contained SF extracts to mimic the SF
environment. The majority of isolates belonged to Betaproteobacteria, more
specifically to the families Comamonadaceae (genera Acidovorax, Curvibacter,
Hydrogenophaga, Simplicispira, Paucibacter, Pelomonas, Piscinibacter and
Rhodoferax) and Oxalobacteraceae (Undibacterium). Additionally, members of
Alphaproteobacteria (Mesorhizobium), Gammaproteobacteria (Aeromonas and
Perlucidibaca) and Actinobacteria (Rhodococcus and Brachybacterium) were
isolated. Several of those genera have only rarely been described, but appear
typical inhabitants of oligotrophic freshwater environments. In this regard, the
Comamonadaceae isolates are of particular interest. Our study shows that bacteria
representative of oligotrophic environments can be isolated using simple
isolation procedures. The isolates provide a microbial framework for extending
our knowledge of the taxonomy, physiology and functionality of oligotrophic
freshwater microbiomes and their interactions with possible invaders.
PMID- 28412536
TI - Molecular phylogenetics and dating of the problematic New Guinea microhylid frogs
(Amphibia: Anura) reveals elevated speciation rates and need for taxonomic
reclassification.
AB - Asterophryinae is a large monophyletic subfamily of Anurans containing over 300
species distributed across one of the world's most geologically active areas -
New Guinea and its satellite islands, Australia and the Philippines. The
tremendous ecological and morphological diversity of this clade, with apparent
specializations for burrowing, terrestrial, semi-aquatic, and arboreal lifestyle,
suggests an evolutionary process of adaptive radiation. Despite this spectacular
diversity, this and many other questions of evolutionary processes have received
little formal study because until now the phylogeny of this spececies-rich clade
has remained uncertain. Here we reconstruct a phylogeny for Asterophryinae with
greatly increased taxon and genetic sampling relative to prior studies. We use
Maximum Likelihood and Bayesian Inference methods to produce the most robust and
comprehensive phylogeny to date containing 155 species using 3 nuclear and 2
mitochondrial loci. We also perform a time calibration analysis to estimate the
age of the clade. We find support for the monophyly of Asterophryinae as well as
need for taxonomic reclassification of several genera. Furthermore, we find
increased rates of speciation across the clade supporting the hypothesis of rapid
radiation. Lastly, we found that adding taxa to the analysis produced more robust
phylogenetic results over adding loci.
PMID- 28412537
TI - Delivering effective science communication: advice from a professional science
communicator.
AB - Science communication is becoming ever more prevalent, with more and more
scientists expected to not only communicate their research to a wider public, but
to do so in an innovative and engaging manner. Given the other commitments that
researchers and academics are required to fulfil as part of their workload
models, it is unfair to be expect them to also instantly produce effective
science communication events and activities. However, by thinking carefully about
what it is that needs to be communicated, and why this is being done, it is
possible to develop high-quality activities that are of benefit to both the
audience and the communicator(s). In this paper, I present some practical advice
for developing, delivering and evaluating effective science communication
initiatives, based on over a decade of experience as being a professional science
communicator. I provide advice regarding event logistics, suggestions on how to
successfully market and advertise your science communication initiatives, and
recommendations for establishing effective branding and legacy.
PMID- 28412538
TI - Saharan dust intrusions in Spain: Health impacts and associated synoptic
conditions.
AB - BACKGROUND: A lot of papers have been published about the impact on mortality of
Sahara dust intrusions in individual cities. However, there is a lack of studies
that analyse the impact on a country and scarcer if in addition the analysis
takes into account the meteorological conditions that favour these intrusions.
OBJECTIVES: The main aim is to examine the effect of Saharan dust intrusions on
daily mortality in different Spanish regions and to characterize the large-scale
atmospheric circulation anomalies associated with such dust intrusions. METHODS:
For determination of days with Saharan dust intrusions, we used information
supplied by the Ministry of Agriculture, Food & Environment, it divides Spain
into 9 main areas. In each of these regions, a representative province was
selected. A time series analysis has been performed to analyse the relationship
between daily mortality and PM10 levels in the period from 01.01.04 to 31.12.09,
using Poisson regression and stratifying the analysis by the presence or absence
of Saharan dust advections. RESULTS: The proportion of days on which there are
Saharan dust intrusions rises to 30% of days. The synoptic pattern is
characterised by an anticyclonic ridge extending from northern Africa to the
Iberian Peninsula. Particulate matter (PM) on days with intrusions are associated
with daily mortality, something that does not occur on days without intrusions,
indicating that Saharan dust may be a risk factor for daily mortality. In other
cases, what Saharan dust intrusions do is to change the PM-related mortality
behaviour pattern, going from PM2.5. CONCLUSIONS: A study such as the one
conducted here, in which meteorological analysis of synoptic situations which
favour Saharan dust intrusions, is combined with the effect on health at a city
level, would seem to be crucial when it comes to analysing the differentiated
mortality pattern in situations of Saharan dust intrusions.
PMID- 28412539
TI - Laparoscopic Reoperative Antireflux Surgery Is More Cost-Effective than Open
Approach.
AB - BACKGROUND: We previously reported on the outcomes of laparoscopic and open
reoperative antireflux surgery. The aim of this study was to compare the costs of
these procedures. STUDY DESIGN: We performed a retrospective review. Financial
and procedure coding data were obtained using a cost accounting system. There
were 49 procedures in 46 patients (36 female and 10 male). There were 38
laparoscopic (including 4 conversions) and 11 open procedures (7 transabdominal
repairs and 4 gastric-preserving Roux-en-Y esophagojejunostomy). Values are
median and interquartile range (IQR) and mean costs. RESULTS: Median age was 54
years (IQR 49 to 67 years) for the laparoscopic group vs 56 years (IQR 50 to 65
years) for the open group (p = 0.675). Mean direct costs per case for the
laparoscopic group vs open group were $12,655 vs $24,636 (p < 0.002); operating
room costs: $3,788 vs $5,547 (p = 0.011); hospital room costs: $1,948 vs $6,438
(p < 0.005); and supply costs: $4,386 vs $5,386 (p = 0.077). Median duration of
the operation for the laparoscopic group was 185 minutes (IQR 147 to 254 minutes)
vs 308 minutes (IQR 259 to 416 minutes) for the open group (p < 0.002). Median
length of stay for the laparoscopic group was 3 days (IQR 2 to 4 days) vs 9 days
(IQR 8 to 14 days) for the open group (p < 0.001). There was no 30-day or in
hospital mortality. Excluding the 4 Roux-en-Y procedures, direct costs for the
laparoscopic group (n = 38) were $12,655 vs $23,678 for the transabdominal group
(n = 7) (p = 0.035); duration of operation: 185 minutes (IQR 147 to 254 minutes)
vs 292 minutes (IQR 218 to 309 minutes) (p = 0.003); and length of stay: 3 days
(IQR 2 to 4 days) vs 9 days (IQR 7 to 15 days) (p = 0.017). There were 3
recurrences in the laparoscopic group. Two were repaired laparoscopically and 1
required a gastric-preserving Roux-en-Y esophagojejunostomy because the patient
had undergone 2 earlier failed repairs. Including the cumulative costs of 3
recurrent hiatal hernia repairs, the driving force to reduce costs remained
length of stay, manifested by the costs of the hospital rooms. CONCLUSIONS:
Laparoscopic reoperative antireflux surgery is more cost-effective than open
repair. The laparoscopic approach, when feasible, should be considered the
surgical option for treatment of recurrent hiatal hernia in specialized
esophageal centers with highly experienced surgical teams.
PMID- 28412540
TI - Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but
not always.
AB - Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs
deputed to non-image forming functions of the eye such as synchronization of
circadian rhythms to light-dark cycle. These cells are characterized by unique
electrophysiological, anatomical and biochemical properties and are usually more
resistant than conventional RGCs to different insults, such as axotomy and
different paradigms of stress. We also demonstrated that these cells are
relatively spared compared to conventional RGCs in mitochondrial optic
neuropathies (Leber's hereditary optic neuropathy and Dominant Optic Atrophy).
However, these cells are affected in other neurodegenerative conditions, such as
glaucoma and Alzheimer's disease. We here review the current evidences that may
underlie this dichotomy. We also present our unpublished data on cell experiments
demonstrating that melanopsin itself does not explain the robustness of these
cells and some preliminary data on immunohistochemical assessment of mitochondria
in mRGCs.
PMID- 28412541
TI - Endothelin polymorphisms as a risk factor for cerebral aneurysm rebleeding
following aneurysmal subarachnoid hemorrhage.
AB - BACKGROUND: Aneurysm rebleeding following presentation with aneurysmal
subarachnoid hemorrhage (aSAH) is associated with high mortality and poor
functional outcome. While a substantial genetic contribution to aneurysm
formation and rupture is known, the genetic influence on the risk of rebleeding
is poorly understood. OBJECTIVE: To evaluate the role of common endothelin
polymorphisms in aneurysm rebleeding. PATIENTS AND METHODS: Blood sample from all
patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study
were used for genetic evaluation. The CARAS study prospectively enrolled aSAH
patients at two academic institutions in the United States from 2012 to 2015.
Common endothelin SNPs were detected using 5'exonnuclease (Taqman) genotyping
assays. Analysis of associations between endothelin single nucleotide
polymorphisms (SNP) and aneurysm rebleeding was performed. RESULTS: One hundred
and forty-nine aSAH patients were included. Acute spontaneous aneurysm rebleeding
occurred in 5 (3.4%) patients. Multivariable analysis identified the TT genotype
for EDN1 G/T SNP (rs2070699; OR 97.4, 95% CI 3.825-2479.984, p=0.006) as an
independent risk factor for aneurysm rebleeding. Aneurysm rebleeding was
associated with an unfavorable functional outcome (mRS 3-6) at last follow up in
all 5 patients. CONCLUSION: Aneurysm rebleeding following presentation with aSAH
was independently associated with the TT genotype of the EDN1 G/T SNP. All
patients with acute spontaneous aneurysm rebleeding suffered a poor functional
outcome at last follow up.
PMID- 28412542
TI - Reduction of retinal nerve fiber layer thickness in vigabatrin-exposed patients:
A meta-analysis.
AB - OBJECTIVE: Vigabatrin (VGB) is currently served as an effective adjunctive
therapy for patients with partial epilepsy worldwide. In this study, meta
analysis was conducted to comprehensively evaluate the changes in peripapillary
retinal nerve fiber layer (RNFL) thickness assessed by optical coherence
tomography (OCT) in epilepsy patients who were treated by VGB. MATERIAL AND
METHODS: Publications on PubMed, Wiley Online Library and the Elsevier Science
databases were searched by September 2016. The statistical analysis was performed
by RevMan 5.3 software. RESULTS: Four studies were identified, and 202 eyes in
VGB-exposed patients (VGB group) as well as 162 eyes in patients who never
received VGB treatment (NON-VGB group) were included. The studies demonstrated
that the total RNFL thickness is attenuated in VGB treated patients (weighted
mean differences in MUm, WMD=-15.96, 95% CI: -23.69 to -8.23, P<0.0001). RNFL
thickness in 3 quadrants were significantly reduced in VGB group: superior (WMD=
18.15, 95% CI: -23.31 to -12.98, P<0.00001), inferior (WMD=-23.19, 95% CI: -32.23
to -14.15, P<0.00001) and nasal (WMD=-19.29, 95% CI: -35.57 to -3.02, P=0.02).
However, the temporal RNFL thickness in these two groups showed no significant
difference: temporal (WMD=-2.41, 95% CI: -6.67 to 1.85, P=0.27). CONCLUSION:
Based on the meta-analysis, RNFL thickness appears to reduce in epilepsy patients
who received VGB treatment, and OCT could be a useful tool to help clinicians
assessing its retinal toxicity and guiding its dosage.
PMID- 28412543
TI - Diabetes and cardiovascular events in high-risk patients: Insights from a
multicenter registry in a middle-income country.
AB - AIMS: The aim of this study was to determine the rate of major clinical events
and its determinants in patients with previous cardiovascular event or not, and
with or without diabetes from a middle-income country. METHODS: REACT study is a
multicenter registry conducted between July 2010 and May 2013 in Brazil. Patients
were eligible if they were over 45years old and high cardiovascular risk.
Patients were followed for 12months; data were collected regarding adherence to
evidence-based therapies and occurrence of clinical events (all-cause mortality,
non-fatal cardiac arrest, myocardial infarction, or stroke). RESULTS: A total of
5006 subjects was included and analyzed in four groups: No diabetes and no
previous cardiovascular event, n=430; diabetes and no previous cardiovascular
event, n=1138; no diabetes and previous cardiovascular event, n=1747; and
diabetes and previous cardiovascular event, n=1691. Major clinical events in one
year follow-up occurred in 332 patients. A previous cardiovascular event was
associated with a higher risk of having another event in the follow-up (HR 2.31
95% CI 1.74-3.05, p<0.001), as did the presence of diabetes (HR 1.28 95% CI 1.10
1.73, p=0.005). In patients with diabetes,failure to reach HbA1c targetswas
related topoorer event-free survival compared to patients with good metabolic
control (HR 1.70 95% CI 1.01-2.84, p=0.044). CONCLUSIONS: In Brazil, diabetes
confers high risk for major clinical events, but this condition is not equivalent
to having a previous cardiovascular event. Moreover, not so strict targets for
HbA1c in patients with diabetes and previous cardiovascular events might be
considered.
PMID- 28412544
TI - Phosphorylation of WHIRLY1 by CIPK14 Shifts Its Localization and Dual Functions
in Arabidopsis.
AB - Plastid-to-nucleus retrograde signaling is critical for normal growth and
development in plants. The dual-function and dual-located ssDNA binding protein
WHIRLY1 (WHY1) has been proposed to coordinate the retrograde signaling from
plastids to the nucleus. However, the regulatory mechanism governing the
functional switch of WHY1 for mediating plastid-to-nucleus retrograde signaling
remains unknown. Here, we report that the Calcineurin B-Like-Interacting Protein
Kinase14 (CIPK14) interacts with and phosphorylates WHY1 in Arabidopsis.
Phosphorylation of WHY1 results in increased accumulation in the nucleus and
enhanced binding with the promoter of WRKY53, which encodes a key transcription
factor regulating leaf senescence in Arabidopsis. Transgenic plants
overexpressing CIPK14 showed an increased nuclear isoform but decreased plastid
isoform of WHY1, among which 95% of transgenic lines showed the stay-green
phenotype and 5% of lines showed the variegated pale-green phenotype.
Interestingly, the phenotypes of both types of transgenic plants could be
recovered by overexpression of plastid-form WHY1. In contrast, knockdown of
CIPK14 caused early senescence and even seedling-lethal phenotypes along with
elevated expression of senescence-related genes such as WRKY53, SAG12, and NDHF
but decreased expression of MER11, RAD50, and POR genes, which could be rescued
by overexpression of CIPK14 but not by overexpressing plastid-form or nuclear
form WHY1; the stay-green plants overexpressing CIPK14 showed reduced expression
of WRKY53, SAG12, NDHF, and large plastid rRNA. Consistently, the accumulation of
nuclear-form WHY1 was significantly reduced in the CIPK14 knockdown lines,
resulting in a low ratio of nuclear-/plastid-form WHY1. Taken together, our
results demonstrate that CIPK14 regulates the phosphorylation and organellar
distributions of WHY1 and pinpoint that CIPK14 may function as a cellular switch
between leaf senescence and plastid development for coordinating the
intercellular signaling in Arabidopsis.
PMID- 28412545
TI - DNA Topoisomerase 1 Prevents R-loop Accumulation to Modulate Auxin-Regulated Root
Development in Rice.
AB - R-loop structures (RNA:DNA hybrids) have important functions in many biological
processes, including transcriptional regulation and genome instability among
diverse organisms. DNA topoisomerase 1 (TOP1), an essential manipulator of DNA
topology during RNA transcription and DNA replication processes, can prevent R
loop accumulation by removing the positive and negative DNA supercoiling that is
made by RNA polymerases during transcription. TOP1 is required for plant
development, but little is known about its function in preventing co
transcriptional R-loop accumulation in various biological processes in plants.
Here we show that knockdown of OsTOP1 strongly affects rice development, causing
defects in root architecture and gravitropism, which are the consequences of
misregulation of auxin signaling and transporter genes. We found that R-loops are
naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1
is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets
the accurate expression levels of auxin-related genes by preventing the
overaccumulation of inherent R-loops. Our data reveal R-loops as important
factors in polar auxin transport and plant root development, and highlight that
OsTOP1 functions as a key to link transcriptional R-loops with plant hormone
signaling, provide new insights into transcriptional regulation of hormone
signaling in plants.
PMID- 28412546
TI - Prefoldins Negatively Regulate Cold Acclimation in Arabidopsis thaliana by
Promoting Nuclear Proteasome-Mediated HY5 Degradation.
AB - The process of cold acclimation is an important adaptive response whereby many
plants from temperate regions increase their freezing tolerance after being
exposed to low non-freezing temperatures. The correct development of this
response relies on proper accumulation of a number of transcription factors that
regulate expression patterns of cold-responsive genes. Multiple studies have
revealed a variety of molecular mechanisms involved in promoting the accumulation
of these transcription factors. Interestingly, however, the mechanisms implicated
in controlling such accumulation to ensure their adequate levels remain largely
unknown. In this work, we demonstrate that prefoldins (PFDs) control the levels
of HY5, an Arabidopsis transcription factor with a key role in cold acclimation
by activating anthocyanin biosynthesis, in response to low temperature. Our
results show that, under cold conditions, PFDs accumulate into the nucleus
through a DELLA-dependent mechanism, where they interact with HY5, triggering its
ubiquitination and subsequent degradation. The degradation of HY5 would result,
in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate
development of cold acclimation. These findings uncover an unanticipated nuclear
function for PFDs in plant responses to abiotic stresses.
PMID- 28412547
TI - Intracellular DNA sensing pathway of cGAS-cGAMP is decreased in human newborns
and young children.
AB - Newborns are highly susceptible to DNA virus infections, which may result from
the characteristics of neonatal innate immune systems. Here we analyzed for the
first time the development of innate immune sensing and signaling of
intracellular DNA virus infection in human newborns and young children. Both mRNA
and protein expression of cGAS, an intracellular DNA sensor, were shown to be
significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In
addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex
virus type 1 (HSV-1) or interferon-alpha (IFNalpha) stimulation. Furthermore,
production of the second messenger cGAMP and activation of the transcriptional
factor IRF3 was severely decreased in neonatal cord blood mononuclear cells
(CBMCs) or PBMCs compared with adults. In contrast, the downstream signaling
STING-TBK1-IRF3 appeared to be functional in neonatal PBMCs, as demonstrated by
the fact that IRF3 phosphorylation and IFNbeta production in these cells could be
activated by cGAMP. Intriguingly, decreased expression of cGAS in neonatal cells
can be rescued by DNA demethylation, with concomitant enhancement in IFNbeta
induction by HSV-1. Thus, cGAS restoration or STING stimulation by small
molecules during infancy might improve the age-dependent susceptibility to DNA
virus infection.
PMID- 28412548
TI - Internal image anti-idiotypic antibody: A new strategy for the development a new
category of prolactin receptor (PRLR) antagonist.
AB - Over the past decades, a number of prolactin receptor (PRLR) antagonists have
been developed, which can be divided into two categories, PRLR analogue and anti
PRLR antibody. However, until now, there have been no commercially available PRLR
antagonists. Here, we described a new approach for the preparation of PRLR
antagonist, namely internal image anti-idiotypic antibody strategy. The hybridoma
technique was used to generate anti-idiotypic antibodies to PRL. Competitive
ELISA, competitive receptor-binding analysis and immunofluorescence assay (IFA)
were then used to screen and characterize anti-idiotypic antibodies to PRL. One
internal image anti-idiotypic antibody, termed MG7, was obtained. A series of
experiments demonstrated that MG7 behaved as a typical internal image anti
idiotypic antibody (Ab2beta). MG7 exhibited effective antagonistic activity,
which not only inhibited PRL binding to PRLR in a dose-dependent manner but also
inhibited PRLR-mediated intracellular signalling. Furthermore, MG7 also blocked
Nb2 cell proliferation induced by PRL. The current study suggests that MG7 has
the potential application in the PRL/PRLR-related studies in future. In addition,
this work also suggests that the internal image anti-idiotypic antibody may
represent a novel strategy for the development of PRLR antagonist.
PMID- 28412549
TI - Enhancing boron rejection in FO using alkaline draw solutions.
AB - This study provides a novel method to enhance boron removal in a forward osmosis
(FO) process. It utilizes the reverse solute diffusion (RSD) of ions from
alkaline draw solutions (DSs) and the concentration polarization of the hydroxyl
ions to create a highly alkaline environment near the membrane active surface.
The results show that boron rejection can be significantly enhanced by increasing
the pH of NaCl DS to 12.5 in the active-layer-facing-feed-solution (AL-FS)
orientation. The effect of RSD enhanced boron rejection was further promoted in
the presence of concentration polarization (e.g., in the active-layer-facing-draw
solution (AL-DS) orientation). The current study opens a new dimension for
controlling contaminant removal by FO using tailored DS chemistry, where the RSD
induced localized water chemistry change is taken advantage in contrast to the
conventional method of chemical dosing to the bulk feed water.
PMID- 28412550
TI - The competition between cathodic oxygen and ozone reduction and its role in
dictating the reaction mechanisms of an electro-peroxone process.
AB - Previous studies indicate that effective generation of hydrogen peroxide (H2O2)
from cathodic oxygen (O2) reduction is critical for the improved water treatment
performance (e.g., enhanced pollutant degradation and reduced bromate formation)
during the electro-peroxone (E-peroxone) process (a combined process of
electrolysis and ozonation). However, undesired reactions (e.g., O3, H2O2, and
H2O reductions) may occur in competition with O2 reduction at the cathode. To get
a better understanding of how these side reactions would affect the process, this
study investigated the cathodic reaction mechanisms during electrolysis with
O2/O3 gas mixture sparging using various electrochemical techniques (e.g., linear
sweep voltammetry and stepped-current chronopotentiometry). Results show that
when a carbon brush cathode was used during electrolysis with O2/O3 sparging, H2O
and H2O2 reductions were usually negligible cathodic reactions. However, O3 can
be preferentially reduced at much more positive potentials (ca. 0.9 V vs. SCE)
than O2 (ca. -0.1 V vs. SCE) at the carbon cathode. Therefore, cathodic O2
reduction was inhibited when the process was operated under current limited
conditions for cathodic O3 reduction. The inhibition of O2 reduction prevented
the desired E-peroxone process (cathodic O2 reduction to H2O2 and ensuing
reaction of H2O2 with O3 to OH) from occurring. In contrast, when cathodic O3
reduction was limited by O3 mass transfer to the cathode, cathodic O2 reduction
to H2O2 could occur, thus enabling the E-peroxone process to enhance pollutant
degradation and mineralization. Many process and water parameters (applied
current, ozone dose, and reactivity of water constituents with O3) can cause
fundamental changes in the cathodic reaction mechanisms, thus profoundly
influencing water treatment performance during the E-peroxone process. To exploit
the benefits of H2O2 in water treatment, reaction conditions should be carefully
controlled to promote cathodic O2 reduction during the E-peroxone process.
PMID- 28412551
TI - A field experiment to evaluate the cleaning performance of sewer flushing on non
uniform sediment deposits.
AB - The results of a field experiment to evaluate the scouring effect of a single
flush operation in a compound-section sewer channel in Paris, France, are
presented in this paper. Full monitoring of the experiment allowed identifying
flush-related transport/deposition key processes playing a role on the evolution
of the deposited sediments. Overall, the flush was able to scour sediments
accumulated over the channel invert up to a significant distance from the gate.
The analysis of the results revealed that the flush had a different impact on the
various sediments present in the bed mixtures, with most of the eroded volume
including sediment particles smaller than the median grain size.
PMID- 28412552
TI - Copper-containing mesoporous bioactive glass nanoparticles as multifunctional
agent for bone regeneration.
AB - : The application of mesoporous bioactive glasses (MBGs) containing controllable
amount of different ions, with the aim to impart antibacterial activity, as well
as stimulation of osteogenesis and angiogenesis, is attracting an increasing
interest. In this contribution, in order to endow nano-sized MBG with additional
biological functions, the framework of a binary SiO2-CaO mesoporous glass was
modified with different concentrations of copper ions (2 and 5%mol.), through a
one-pot ultrasound-assisted sol-gel procedure. The Cu-containing MBG (2%mol.)
showed high exposed surface area (550m2g-1), uniform mesoporous channels (2.6nm),
remarkable in vitro bioactive behaviour and sustained release of Cu2+ ions. Cu
MBG nanoparticles and their ionic dissolution extracts exhibited antibacterial
effect against three different bacteria strains, E. coli, S. aureus, S.
epidermidis, and the ability to inhibit and disperse the biofilm produced by S.
epidermidis. The obtained results suggest that the developed material, which
combines in single multifunctional agent excellent bioactivity and antimicrobial
ability, offers promising opportunities for the prevention of infectious diseases
and the effective treatment of bone defects. STATEMENT OF SIGNIFICANCE: In order
to endow mesoporous bioactive glass, characterized by excellent bioactive
properties, with additional biological functions, Cu-doped mesoporous SiO2-CaO
glass (Cu-MBG) in the form of nanoparticles was prepared by an ultra-sound
assisted one pot synthesis. The analysis of the bacterial viability, using
different bacterial strains, and the morphological observation of the biofilm
produced by the Staphylococcus epidermidis, revealed the antimicrobial
effectiveness of the Cu-MBG and the relative ionic extracts against both the
bacterial growth and the biofilm formation/dispersion, providing a true
alternative to traditional antibiotic systemic therapies. The proposed
multifunctional agent represents a promising and versatile platform for bone and
soft tissues regeneration.
PMID- 28412553
TI - Native and solubilized decellularized extracellular matrix: A critical assessment
of their potential for improving the expansion of mesenchymal stem cells.
AB - : Capturing the promise of mesenchymal stem cell (MSC)-based treatments is
currently limited by inefficient production of cells needed for clinical
therapies. During conventional ex vivo expansion, a large portion of MSCs lose
the properties that make them attractive for use in cell therapies.
Decellularized extracellular matrix (dECM) has recently emerged as a promising
substrate for the improved expansion of MSCs. MSCs cultured on these surfaces
exhibit improved proliferation capacity, maintenance of phenotype, and increased
differentiation potential. Additionally, these dECMs can be solubilized and used
to coat new cell culture surfaces, imparting key biological properties of the
native matrices to other surfaces such as tissue engineering scaffolds. Although
this technology is still developing, there is potential for an impact in the
fields of MSC biology, biomaterials, tissue engineering, and therapeutics. In
this article, we review the role of dECM in MSC expansion by first detailing the
decellularization methods that have been used to produce the dECM substrates;
discussing the shortcomings of current decellularization methods; describing the
improved MSC characteristics obtained when the cells are cultured on these
surfaces; and considering the effect of the passage number, age of donor, and
dECM preparation method on the quality of the dECM. Finally we describe the
critical roadblocks that must be addressed before this technology can fulfil its
potential, including elucidating the mechanism by which the dECMs improve the
expansion of primary MSCs and the identification of a readily available source of
dECM. STATEMENT OF SIGNIFICANCE: Current mesenchymal stem cell (MSC) culture
methods result in premature cellular senescence or loss of differentiation
potential. This creates a major bottleneck in their clinical application, as
prolonged expansion is necessary to achieve clinically relevant numbers of cells.
Recently, decellularized extracellular matrix (dECM) produced by primary MSC has
emerged as an attractive substrate for the improved expansion of MSC; cells
cultured on these surfaces retain their desired stem cell characteristics for
prolonged times during culture. This review article describes the inception and
development of this dECM-based technology, points out existing challenges that
must be addressed, and suggests future directions of research. To our knowledge,
this is the first review written on the use of dECM for improved mesenchymal stem
cell expansion.
PMID- 28412554
TI - Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin
nanofiber hydrogel.
AB - : Fibrin plays a crucial role in peripheral nerve regeneration, which could occur
spontaneously in the format of longitudinally oriented fibrin cables during the
initial stage of nerve regeneration. This fibrin cable can direct migration and
proliferation of Schwann cells and axonal regrowth, which is very important to
nerve regeneration. In the present study, we prepared a three-dimensional
hierarchically aligned fibrin nanofiber hydrogel (AFG) through electrospinning
and molecular self-assembly to resemble the architecture and biological function
of the native fibrin cable. The AFG displayed a hierarchically aligned topography
as well as low elasticity (~1.5kPa) that were similar to nerve extracellular
matrix (ECM) and the native fibrin cable. Rapid, directional cell adhesion and
migration of Schwann cells (SCs) and dorsal root ganglions were observed in
vitro. The AFG was then used as a potential intraluminal substrate in a
bioengineered chitosan tube to bridge a 10-mm-long sciatic nerve gap in rats. We
found that the AFG served as a beneficial microenvironment to support SCs cable
formation and axonal regrowth within 2weeks. Further histological and
morphological analyses as well as electrophysiological and functional
examinations were performed after AFG implantation for up to 12weeks. The results
from morphological analysis and electrophysiological examination indicated that
regenerative outcomes achieved by our developed graft were close to those by an
autologous nerve graft, but superior to those by hollow chitosan tubes (hCST) and
random fibrin nanofiber hydrogel (RFG). Our results demonstrate that the AFG
creates an instructive microenvironment by mimicking the native fibrin cable as
well as the oriented and soft features of nerve ECM to accelerate axonal
regrowth, thus showing great promising potential for applications in neural
regeneration. STATEMENT OF SIGNIFICANCE: In peripheral nervous system defect
repair, a wide variety of strategies have been proposed for preparing
functionalized nerve guidance conduits (NGC) with more complex configurations to
obtain optimal repair effects. Longitudinally oriented fibrin cables were
reported to form spontaneously during the initial stages of peripheral nerve
regeneration in an empty NGC, which can direct the migration and proliferation of
Schwann cells and promote axonal regrowth. Therefore, based on the biomimetic
idea, we prepared a three-dimensional hierarchically aligned fibrin nanofiber
hydrogel (AFG) through electrospinning and molecular self-assembly, resembling
the architecture and biological function of the native fibrin cable and serving
as an intraluminal filling to accelerate axon regeneration. We found that the AFG
was a beneficial microenvironment to support SCs cable formation and accelerate
axonal regrowth with improved motor functional recovery.
PMID- 28412555
TI - One-dimensional poly(L-lysine)-block-poly(L-threonine) assemblies exhibit potent
anticancer activity by enhancing membranolysis.
AB - : Herein, we report the oncolytic activity of cationic, one-dimensional (1D)
fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine)
(PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can
efficiently interact with negatively charged cellular and mitochondrial membranes
via electrostatic interactions, leading to necrosis via membrane lysis and
apoptosis via the mitochondria-lytic effect. The concept is analogous to that of
1D drug carriers that exhibit enhanced cell penetration. In comparison to free
PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward
cancer cells, low hemolysis activity, enhanced membranolytic activity, and a
different apoptosis pathway, which may be due to differences in the peptide
membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma
model indicate that the fibril assemblies significantly inhibited tumor growth,
improved survival in tumor-bearing mice and suppressed lung metastasis without
obvious body weight loss. An additive efficacy was also observed for treatment
with both PLL-b-PLT and cisplatin. These results support the feasibility of using
1D fibril assemblies as potential apoptotic anticancer therapeutics. STATEMENT OF
SIGNIFICANCE: We report that cationic, one-dimensional (1D) fibril assemblies
formed by coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block
copolypeptides exhibited potent anticancer activity by enhancing membranolysis.
The 1D fibril assemblies can efficiently interact with negatively charged
cellular and mitochondrial membranes via electrostatic interactions, leading to
necrosis via membrane lysis and apoptosis via mitochondria-lytic effect.
Moreover, the fibril assemblies exhibited low hemolytic activity and selective
cytotoxicity toward cancer cell, which is advantageous as compared to PLL and
most antimicrobial/anticancerous peptides. This study provides a new concept of
using cationic, 1D fibril assemblies for cancer therapy.
PMID- 28412556
TI - Synchronized movement experience enhances peer cooperation in preschool children.
AB - Cooperating with other people is a key achievement in child development and is
essential for human culture. We examined whether we could induce 4-year-old
children to increase their cooperation with an unfamiliar peer by providing the
peers with synchronized motion experience prior to the tasks. Children were
randomly assigned to independent treatment and control groups. The treatment of
synchronous motion caused children to enhance their cooperation, as measured by
the speed of joint task completion, compared with control groups that underwent
asynchronous motion or no motion at all. Further analysis suggested that
synchronization experience increased intentional communication between peer
partners, resulting in increased coordination and cooperation.
PMID- 28412557
TI - Electroconvulsive therapy changes the regional resting state function measured by
regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) in
elderly major depressive disorder patients: An exploratory study.
AB - Electroconvulsive therapy (ECT) is the most effective and rapid treatment for
severe major depressive disorder (MDD) in elderly patients. The mechanism of ECT
is unclear, and studies on ECT in elderly MDD patients by resting-state
functional magnetic resonance imaging are rare. Thirteen elderly MDD patients
were scanned before and after ECT using a 3.0T MRI scanner. Regional homogeneity
(ReHo) and amplitude of low-frequency fluctuations (ALFF) were processed to
compare resting-state function before and after treatment. Depression and anxiety
symptoms of all patients abated after ECT. Decreased ReHo values in the bilateral
superior frontal gyrus (SFG) were observed after ECT, and the values of right SFG
significantly correlated with an altered Hamilton depression rating scale score.
Increased ALFF values in the left middle frontal gyrus, right middle frontal
gyrus, orbital part, and decreased ALFF values in the left midcingulate area,
left precentral gyrus, right SFG/middle frontal gyrus after ECT were also
observed. These results support the hypothesis that ECT may affect the regional
resting state brain function in geriatric MDD patients.
PMID- 28412558
TI - Relationship of mindful awareness to neural processing of angry faces and impact
of mindfulness training: A pilot investigation.
AB - Mindfulness is paying attention, non-judgmentally, to experience in the moment.
Mindfulness training reduces depression and anxiety and influences neural
processes in midline self-referential and lateralized somatosensory and executive
networks. Although mindfulness benefits emotion regulation, less is known about
its relationship to anger and the corresponding neural correlates. This study
examined the relationship of mindful awareness and brain hemodynamics of angry
face processing, and the impact of mindfulness training. Eighteen healthy
volunteers completed an angry face processing fMRI paradigm and measurement of
mindfulness and anger traits. Ten of these participants were recruited from a
Mindfulness-Based Stress Reduction (MBSR) class and also completed imaging and
other assessments post-training. Self-reported mindful awareness increased after
MBSR, but trait anger did not change. Baseline mindful awareness was negatively
related to left inferior parietal lobule activation to angry faces; trait anger
was positively related to right middle frontal gyrus and bilateral angular gyrus.
No significant pre-post changes in angry face processing were found, but changes
in trait mindful awareness and anger were associated with sub-threshold
differences in paralimbic activation. These preliminary and hypothesis-generating
findings, suggest the analysis of possible impact of mindfulness training on
anger may begin with individual differences in angry face processing.
PMID- 28412559
TI - Interictal ripples nested in epileptiform discharge help to identify the
epileptogenic zone in neocortical epilepsy.
AB - OBJECTIVE: This study aimed to identify the subtype of interictal ripples that
help delineate the epileptogenic zone in neocortical epilepsy. METHODS: Totally
25 patients with focal neocortical epilepsy who had invasive
electroencephalography (EEG) evaluation and subsequent surgery were included.
They were followed up for at least 2years. Interictal ripples (80-250Hz) and fast
ripples (250-500Hz) during slow-wave sleep were identified. Neocortical ripples
were defined as type I ripples when they were superimposed on epileptiform
discharges, and as type II ripples when they occurred independently. Resection
ratio was calculated to present the extent to which the cortical area showing an
interictal event or the seizure onset zone (SOZ) was completely removed. RESULTS:
Fast ripples and types I and II ripples were found in 8, 19, and 21 patients,
respectively. Only the higher resection ratio of interictal fast or type I
ripples was correlated to the Engel 1a surgical outcome. CONCLUSIONS: Type I
ripples could assist in localizing the epileptogenic zone in neocortical
epilepsy. SIGNIFICANCE: Type I and fast ripples both may be pathological high
frequency oscillations.
PMID- 28412560
TI - Comparison of minimally invasive spine surgery using intraoperative computed
tomography integrated navigation, fluoroscopy, and conventional open surgery for
lumbar spondylolisthesis: a prospective registry-based cohort study.
AB - BACKGROUND CONTEXT: To date, the surgical approaches for the treatment of lumbar
spondylolisthesis by transforaminal lumbar interbody fusion (TLIF) using
minimally invasive spine surgery assisted with intraoperative computed tomography
image-integrated navigation (MISS-iCT), fluoroscopy (MISS-FS), and conventional
open surgery (OS) are debatable. PURPOSE: This study compared TLIF using MISS
iCT, MISS-FS, and OS for treatment of one-level lumbar spondylolisthesis. STUDY
DESIGN: This is a prospective, registry-based cohort study that compared surgical
approaches for patients who underwent surgical treatment for one-level lumbar
spondylolisthesis. PATIENT SAMPLE: One hundred twenty-four patients from January
2010 to March 2012 in a medical center were recruited. OUTCOME MEASURES: The
outcome measures were clinical assessments, including Short-Form 12, visual
analog scale (VAS), Oswestry Disability Index, Core Outcome Measurement Index,
and patient satisfaction, and blood loss, hospital stay, operation time,
postoperative pedicle screw accuracy, and superior-level facet violation.
METHODS: All surgeries were performed by two senior surgeons together. Ninety
nine patients (40M, 59F) who had at least 2 years' follow-up were divided into
three groups according to the operation methods: MISS-iCT (N=24), MISS-FS (N=23),
and OS (N=52) groups. Charts and surgical records along with postoperative CT
images were assessed. RESULTS: MISS-iCT and MISS-FS demonstrated a significantly
lowered blood loss and hospital stay compared with OS group (p<.01). Operation
time was significantly lower in the MISS-iCT and OS groups compared with the MISS
FS group (p=.002). Postoperatively, VAS scores at 1 year and 2 years were
significantly improved in the MISS-iCT and MISS-FS groups compared with the OS
groups. No significant difference in the number of pedicle screw breach (>2 mm)
was found. However, a lower superior-level facet violation rate was observed in
the MISS-iCT and OS groups (p=.049). CONCLUSIONS: MISS-iCT TLIF demonstrated
reduced operation time, blood loss, superior-level facet violation, hospital
stay, and improved functional outcomes compared with the MISS-FS and OS
approaches.
PMID- 28412562
TI - Effectiveness of telehealth-based interventions in the management of non-specific
low back pain: a systematic review with meta-analysis.
AB - BACKGROUND: Telehealth has emerged as a potential alternative to deliver
interventions for low back pain (LBP); however, its effectiveness has not been
investigated. PURPOSE: The aim of this review was to evaluate whether
interventions delivered by telehealth improve pain, disability, function, and
quality of life in non-specific LBP. STUDY DESIGN: This is a systematic review
with meta-analysis. METHODS: Seven databases were searched from the earliest
records to August 2015. Eligible studies were randomized controlled trials that
investigated the effectiveness of telehealth-based interventions, solo or in
combination with other interventions, for non-specific LBP compared with a
control group. Trials deemed clinically homogeneous were grouped in meta
analyses. RESULTS: Eleven studies were included (n=2,280). In chronic LBP,
telehealth interventions had no significant effect on pain at short-term follow
up (four trials: 1,089 participants, weighted mean difference [WMD]: -2.61
points, 95% confidence interval [CI]: -5.23 to 0.01) or medium-term follow-up
(two trials: 441 participants, WMD: -0.94 points, 95% CI: -6.71 to 4.84) compared
with a control group. Similarly, there was no significant effect for disability.
Results from three individual trials showed that telehealth was superior to a
control intervention for improving quality of life. Interventions combining
telehealth and usual care were more beneficial than usual care alone in people
with recent onset of LBP symptoms. CONCLUSION: There is moderate-quality evidence
that current telehealth interventions, alone, are not more effective than minimal
interventions for reducing pain and disability in chronic LBP. To date, modern
telehealth media (eg, apps) and telehealth as an adjunct to usual care remain
understudied.
PMID- 28412561
TI - Metastatic human breast cancer to the spine produces mechanical hyperalgesia and
gait deficits in rodents.
AB - BACKGROUND CONTEXT: Metastases to the spine are a common source of severe pain in
cancer patients. The secondary effects of spinal metastases include pain, bone
fractures, hypercalcemia, and neurological deficits. As the disease progresses,
pain severity can increase until it becomes refractory to medical treatments and
leads to a decreased quality of life for patients. A key obstacle in the study of
pain-induced spinal cancer is the lack of reliable and reproducible spine cancer
animal models. In the present study, we developed a reproducible and reliable rat
model of spinal cancer using human-derived tumor tissue to evaluate neurological
decline using imaging and behavioral techniques. PURPOSE: The present study
outlines the development and characterization of an orthotopic model of human
breast cancer to the spine in immunocompromised rats. STUDY DESIGN/SETTING: This
is a basic science study. METHODS: Female immunocompromised rats were randomized
into three groups: tumor (n=8), RBC3 mammary adenocarcinoma tissue engrafted in
the L5 vertebra body; sham (n=6), surgery performed but not tumor engrafted; and
control (n=6), naive rats, no surgery performed. To evaluate the neurological
impairment due to tumor invasion, functional assessment was done in all rodents
at day 40 after tumor engraftment using locomotion gait analysis and pain
response to a mechanical stimulus (Randall-Selitto test). Bioluminescence (BLI)
was used to evaluate tumor growth in vivo and cone beam computed tomography
(CBCT) was performed to evaluate bone changes due to tumor invasion. The animals
were euthanized at day 45 and their spines were harvested and processed for
hematoxylin and eosin (H&E) staining. RESULTS: Tumor growth in the spine was
confirmed by BLI imaging and corroborated by histological analysis. Cone beam
computed tomography images were characterized by a decrease in the bone intensity
in the lumbar spine consistent with tumor location on BLI. On H&E staining of
tumor-engrafted animals, there was a near-complete ablation of the ventral and
posterior elements of the L5 vertebra with severe tumor invasion in the bony
components displacing the spinal cord. Locomotion gait analysis of tumor
engrafted rats showed a disruption in the normal gait pattern with asignificant
reduction in length (p=.02), duration (p=.002), and velocity (p=.002) of right
leg strides and only in duration (p=.0006) and velocity (p=.001) of left leg
strides, as compared with control and sham rats. Tumor-engrafted animals were
hypersensitive to pain stimulus shown as a significantly reduced response in time
(p=.02) and pressure (p=.01) applied when compared with control groups.
CONCLUSIONS: We developed a system for the quantitative analysis of pain and
locomotion in an animal model of metastatic human breast cancer of the spine.
Tumor-engrafted animals showed locomotor and sensory deficits that are in
accordance with clinical manifestation in patients with spine metastasis. Pain
response and locomotion gait analysis were performed during follow-up. The
Randall-Selitto test was a sensitive method to evaluate pain in the rat's spine.
We present a model for the study of bone-associated cancer pain secondary to
cancer metastasis to the spine, as well as for the study of new therapies and
treatments to lessen pain from metastatic cancer to the neuroaxis.
PMID- 28412563
TI - How are patients influenced when counseled for minimally invasive lumbar spine
surgeries? A stepwise model assessing pivotal information for decision-making.
AB - BACKGROUND CONTEXT: Although minimally invasive surgery (MIS)-transforaminal
lumbar interbody fusion (TLIF) has many evidence-based short-term benefits over
open TLIF, both procedures have similar long-term outcomes. Patients' preference
for MIS over open TLIF may be confounded by a lack of understanding of what each
approach entails. PURPOSE: The study aimed to identify the various factors
influencing patients' choice between MIS and open TLIF. STUDY DESIGN/SETTING:
This is a cross-sectional study conducted at a tertiary health-care institution.
PATIENT SAMPLE: Patients, for whom TLIF procedures were indicated, were recruited
over a 3-month period from specialist outpatient clinics. OUTCOME MEASURE: The
outcome measure was patients' choice of surgical approach (MIS or open). METHODS:
All patients were subjected to a stepwise interviewing process and were asked to
select between open and MIS approaches at each step. Further subgroup analysis
stratifying subjects based on stages of decision-making was performed to identify
key predictors of selection changes. No sources of funding were required for this
study and there are no conflicts of interests. RESULTS: Fifty-four patients with
a mean age of 55.8 years participated in the study. Thirteen (24.1%) consistently
selected a single approach, whereas 31 (57.4%) changed their selection more than
once during the interviewing process. Overall, 12 patients (22.2%) had a final
decision different from their initial choice, and 15 patients (27.8%) were unable
to decide. A large proportion of patients (65.0%) initially favored the open
approach's midline incision. This proportion dropped to 16.7% (p<.001) upon
mention of the term MIS. The proportion of patients favoring MIS dropped
significantly following discussion on the pros and cons (p=.002) of each
approach, as well as conversion or revision surgery (p=.017). Radiation and
cosmesis were identified as the two most important factors influencing patients'
final decisions. CONCLUSIONS: The longer midline incision of the open approach is
cosmetically more appealing to patients than the paramedian stab wounds of MIS.
The advantages of the MIS approach may not be as valued by patients as they are
by surgeons. Given the equivalent long-term outcomes of both approaches, it is
crucial that patients are adequately informed during preoperative counseling to
achieve the best consensus decision.
PMID- 28412564
TI - Outcomes of patients with syringomyelia undergoing spine deformity surgery: do
large syrinxes behave differently from small?
AB - BACKGROUND CONTEXT: A paucity of data exists studying outcomes of patients with
syringomyelia undergoing spinal deformity correction. The literature does not
stratify patients by syrinx size, which is likely a major contributor to
outcomes. PURPOSE: The study aimed to compare differences in outcomes between
patients with large (>=4 mm) and small syrinxes (<4 mm) undergoing spinal
deformity correction. DESIGN: This is a retrospective review. PATIENT SAMPLE: The
sample included 28 patients (11 with large syrinx [LS, >4 mm] and 17 with small
syrinx [SS, <4 mm]). OUTCOME MEASURES: The outcome measures were radiographic,
operative, and neurophysiological measures. METHODS: We retrospectively reviewed
28 patients with syringomyelia who underwent spine deformity surgery with 2-year
follow-up. Demographic, surgical, and radiographic data were collected and
compared preoperatively and at 2 years. RESULTS: The LS group (11 patients)
trended toward more left-sided thoracic curves (36% vs. 18%, p=.38) and was more
likely to have had a Chiari decompression (45% vs. 12%, p=.08). The LS patients
had larger preoperative major curves (LS=66 degrees vs. SS=57 degrees , p=.05),
more thoracic kyphosis (LS=42 degrees , SS=24 degrees , p<.01), and greater rib
prominences (LS=16 degrees , SS=13 degrees , p=.04). The LS patients had more
levels fused (LS=12.2, SS=11.2, p=.05), higher estimated blood loss (EBL)
(LS=1068 cc, SS=832 cc, p=.04), and a trend toward less percent correction of the
major curve (LS=57%, SS=65%, p=.18). Four of 11 LS patients (36%) did not have
somatosensory evoked potentials, and one of these also did not have motor evoked
potentials. Neuromonitoring changes occurred in 3 of 11 (27%) LS patients and in
none of the SS patients, with no postoperative deficits. CONCLUSIONS: Outcomes of
patients with syringomyelia undergoing spine deformity surgery are dependent on
the size of the syrinx. Those with large syringomyelia are fused longer with more
EBL and less correction. Spine surgeons should be aware that these patients are
more likely to have less reliable neuromonitoring, with a higher chance of
experiencing a change.
PMID- 28412565
TI - The use of a novel perfusion-based cadaveric simulation model with cerebrospinal
fluid reconstitution comparing dural repair techniques: a pilot study.
AB - BACKGROUND CONTEXT: Watertight dural repair is crucial for both incidental
durotomy and closure after intradural surgery. PURPOSE: The study aimed to
describe a perfusion-based cadaveric simulation model with cerebrospinal fluid
(CSF) reconstitution and to compare spine dural repair techniques. STUDY
DESIGN/SETTING: The study is set in a fresh tissue dissection laboratory. SAMPLE
SIZE: The sample includes eight fresh human cadavers. OUTCOME MEASURES: A
watertight closure was achieved when pressurized saline up to 40 mm Hg did not
cause further CSF leakage beyond the suture lines. METHODS: Fresh human cadaveric
specimens underwent cannulation of the intradural cervical spine for intrathecal
reconstitution of the CSF system. The cervicothoracic dura was then exposed from
C7-T12 via laminectomy. The entire dura was then opened in six cadavers
(ALLSPINE) and closed with 6-0 Prolene (n=3) or 4-0 Nurolon (n=3), and
pressurized with saline via a perfusion system to 60 mm Hg to check for leakage.
In two cadavers (INCISION), six separate 2-cm incisions were made and closed with
either 6-0 Prolene or 4-0 Nurolon, and then pressurized. A hydrogel sealant was
then added and the closure was pressurized again to check for further leakage.
RESULTS: Spinal laminectomy with repair of intentional durotomy was successfully
performed in eight cadavers. The operative microscope was used in all cases, and
the model provided a realistic experience of spinal durotomy repair. For ALLSPINE
cadavers (mean: 240 mm dura/cadaver repaired), the mean pressure threshold for
CSF leakage was observed at 66.7 (+/-2.9) mm Hg in the 6-0 Prolene group and at
43.3 (+/-14.4) mm Hg in the 4-0 Nurolon group (p>.05). For INCISION cadavers, the
mean pressure threshold for CSF leakage without hydrogel sealant was
significantly higher in 6-0 Prolene group than in the 4-0 Nurolon group (6-0
Prolene: 80.0+/-4.5 mm Hg vs. 4-0 Nurolon: 32.5+/-2.7 mm Hg; p<.01). The mean
pressure threshold for CSF leakage with the hydrogel sealants was not
significantly different (6-0 Prolene: 100.0+/-0.0 mm Hg vs. 4-0 Nurolon: 70.0+/
33.1 mm Hg). The use of a hydrogel sealant significantly increased the pressure
thresholds for possible CSF leakage in both the 6-0 Prolene group (p=.01) and the
4-0 Nurolon group (p<.01) when compared with mean pressures without the hydrogel
sealant. CONCLUSIONS: We described the feasibility of using a novel cadaveric
model for both the study and training of watertight dural closure techniques. 6-0
Prolene was observed to be superior to 4-0 Nurolon for watertight dural closure
without a hydrogel sealant. The use of a hydrogel sealant significantly improved
watertight dural closures for both 6-0 Prolene and 4-0 Nurolon groups in the
cadaveric model.
PMID- 28412566
TI - Removal mechanisms of benzotriazoles in duckweed Lemna minor wastewater treatment
systems.
AB - The fate of five benzotriazoles (1H-benzotriazole, BTR; 4-methyl-1H
benzotriazole, 4TTR; 5-methyl-1H-benzotriazole, 5TTR; xylytriazole, XTR and 5
chlorobenzotriazole, CBTR) was studied in batch and continuous-flow Lemna minor
systems and the role of different mechanisms on their removal was evaluated.
Single and joint toxicity experiments were initially conducted using the
Organization for Economic Co-operation and Development (OECD) protocol 221 and no
inhibition on specific growth rate of Lemna minor was observed for concentrations
up to 200MUgL-1. All tested substances were significantly removed in batch
experiments with Lemna minor. Excepting 4TTR, full elimination of CBTR, XTR, 5TTR
and BTR was observed up to the end of these experiments (36d), while the half
life values ranged between 1.6+/-0.3d (CBTR) and 25+/-3.6d (4-TTR). Calculation
of kinetic constants for hydrolysis, photodegradation, and plant uptake revealed
that for all BTRs the kinetic constants of plant uptake were by far higher
comparing to those of the other mechanisms, reaching 0.394+/-0.161d-1 for CBTR.
The operation of a continuous-flow Lemna minor system consisted of three mini
ponds and a total hydraulic residence time of 8.3d showed sufficient removal for
most target substances, ranging between 26% (4TTR) and 72% (CBTR). Application of
a model for describing micropollutants removal in the examined system showed that
plant uptake was the major mechanism governing BTRs removal in Lemna minor
systems.
PMID- 28412567
TI - Leachate treatment in landfills is a significant N2O source.
AB - The importance of methane (CH4) emissions from landfills has been extensively
documented, while the nitrous oxide (N2O) emissions from landfills are considered
negligible. In this study, three landfills were selected to measure CH4 and N2O
emissions using the static chamber method. Dongbu (DB) and Dongfu (DF) landfills,
both located in Xiamen city, Fujian Province, were classified as sanitary. The
former started to receive solid waste from Xiamen city in 2009, and the latter
was closed in 2009. Nanjing (NJ) landfill, located in Nanjing county, Fujian
Province, was classified as managed. Results showed that for the landfill
reservoirs, CH4 emissions were significant, while N2O emissions occurred mainly
in operating areas (on average, 16.3 and 19.0mgN2Om-2h-1 for DB and NJ landfills,
respectively) and made a negligible contribution to the total greenhouse gas
emissions in term of CO2 equivalent. However, significant N2O emissions were
observed in the leachate treatment systems of sanitary landfills and contributed
72.8% and 45.6% of total emissions in term of CO2 equivalent in DB and DF
landfills, respectively. The N2O emission factor (EF) of the leachate treatment
systems was in the range of 8.9-11.9% of the removed nitrogen. The total N2O
emissions from the leachate treatment systems of landfills in Xiamen city were
estimated to be as high as 8.55gN2O-Ncapita-1yr-1. These results indicated that
N2O emissions from leachate treatment systems of sanitary landfills were not
negligible and should be included in national and/or local inventories of
greenhouse gas emissions.
PMID- 28412568
TI - First report on MRSA CC398 recovered from wild boars in the north of Portugal.
Are we facing a problem?
AB - The aim of the present study was to evaluate the resistance of Staphylococcus
aureus recovered from wild boars, to analyze their genetic lineages, and to
investigate the susceptibility to oxacillin. Samples from mouth and nose of 45
wild boars (Sus scrofa) were collected during hunt activity from November 2012 to
January 2013 in the North of Portugal. S. aureus isolates were recovered from 30
of these samples (33%); one isolate/sample was further studied. The
susceptibility of the isolates was tested by disk-diffusion test against 14
antimicrobial agents and minimal inhibitory concentration was used to test
oxacillin according to EUCAST guidelines. The genetic lineages of S. aureus were
characterized by agr-typing, spa-typing and MLST. From the 30 isolates, 18 S.
aureus were susceptible to all antibiotics tested and 7 presented resistance to
one or more of the following antibiotics: penicillin (n=3), oxacillin (n=4),
cefoxitin (n=1), clindamycin (n=2), gentamicin (n=1), fusidic acid (n=1),
ciprofloxacin (n=2), tetracycline (n=1) and linezolid (n=1). One MRSA CC398 (spa
type t899) isolate was detected (oxacillin MIC=32mg/L and mecA-positive), which
presented resistance to penicillin, tetracycline, and ciprofloxacin and contained
the genes of immune evasion cluster (IEC) system (type B). The 29 methicillin
susceptible isolates were typed as ST1 (t1533), ST133 (t3583), ST1643 (t10712),
ST2328 (t3750) and the new STs (3220, 3222, 3223, 3224) associated to new spa
types t14311 and t14312. The agr-types I, II, III and IV were identified. It is a
matter of concern when MRSA and some specific lineages of S. aureus are taken as
commensal habitants of the skin and nose of wild animals and are characterized
with resistance to various antimicrobial agents in clinical use.
PMID- 28412569
TI - A comparison of the abilities of the USLE-M, RUSLE2 and WEPP to model event
erosion from bare fallow areas.
AB - Traditionally, the Universal Soil Loss Equation (USLE) and the revised version of
it (RUSLE) have been applied to predicting the long term average soil loss
produced by rainfall erosion in many parts of the world. Overtime, it has been
recognized that there is a need to predict soil losses over shorter time scales
and this has led to the development of WEPP and RUSLE2 which can be used to
predict soil losses generated by individual rainfall events. Data currently
exists that enables the RUSLE2, WEPP and the USLE-M to estimate historic soil
losses from bare fallow runoff and soil loss plots recorded in the USLE database.
Comparisons of the abilities of the USLE-M and RUSLE2 to estimate event soil
losses from bare fallow were undertaken under circumstances where both models
produced the same total soil loss as observed for sets of erosion events on 4
different plots at 4 different locations. Likewise, comparisons of the abilities
of the USLE-M and WEPP to model event soil loss from bare fallow were undertaken
for sets of erosion events on 4 plots at 4 different locations. Despite being
calibrated specifically for each plot, WEPP produced the worst estimates of event
soil loss for all the 4 plots. Generally, the USLE-M using measured runoff to
calculate the product of the runoff ratio, storm kinetic energy and the maximum
30-minute rainfall intensity produced the best estimates. As to be expected,
ability of the USLE-M to estimate event soil loss was reduced when runoff
predicted by either RUSLE2 or WEPP was used. Despite this, the USLE-M using
runoff predicted by WEPP estimated event soil loss better than WEPP. RUSLE2 also
outperformed WEPP.
PMID- 28412570
TI - Ecology: Science or philately? An interdisciplinary analysis of sustainability by
exploring if it is possible to get more and more information by reducing
collateral environmental damages.
AB - We herein explore the connections between the current condition of ecology
concerning to sustainable development and the statement of Rutherford regarding
the importance of physics to understand sustainability and biological
conservation. The recent emergence of organic biophysics of ecosystems (OBEC) may
constitute a feasible alternative to fill the gap between conventional ecological
thinking and physics, especially thermodynamics. However, our comprehension of
sustainability and biological conservation is influenced by the interactions
between information and entropy, because we tend to exclude parts of the
biosphere as well as their relationships among them. We explore the use of a
holistic analysis of sustainability and biological conservation using physics,
and also establish a parallelism between Maxwell's demons and human beings.
Lastly, the ecological meaning of the hypothetical feasibility of Maxwell's demon
at the anthroposphere scale is analyzed starting from the objections of von
Smoluchowski, Szilard and Bennet.
PMID- 28412571
TI - Thrombolytic and fibrinogenolytic properties of bioconjugate streptokinase
polyamidoamine dendrimers in vitro.
PMID- 28412572
TI - Quantitative analysis of patients with celiac disease by video capsule endoscopy:
A deep learning method.
AB - BACKGROUND: Celiac disease is one of the most common diseases in the world.
Capsule endoscopy is an alternative way to visualize the entire small intestine
without invasiveness to the patient. It is useful to characterize celiac disease,
but hours are need to manually analyze the retrospective data of a single
patient. Computer-aided quantitative analysis by a deep learning method helps in
alleviating the workload during analysis of the retrospective videos. METHOD:
Capsule endoscopy clips from 6 celiac disease patients and 5 controls were
preprocessed for training. The frames with a large field of opaque extraluminal
fluid or air bubbles were removed automatically by using a pre-selection
algorithm. Then the frames were cropped and the intensity was corrected prior to
frame rotation in the proposed new method. The GoogLeNet is trained with these
frames. Then, the clips of capsule endoscopy from 5 additional celiac disease
patients and 5 additional control patients are used for testing. The trained
GoogLeNet was able to distinguish the frames from capsule endoscopy clips of
celiac disease patients vs controls. Quantitative measurement with evaluation of
the confidence was developed to assess the severity level of pathology in the
subjects. RESULTS: Relying on the evaluation confidence, the GoogLeNet achieved
100% sensitivity and specificity for the testing set. The t-test confirmed the
evaluation confidence is significant to distinguish celiac disease patients from
controls. Furthermore, it is found that the evaluation confidence may also relate
to the severity level of small bowel mucosal lesions. CONCLUSIONS: A deep
convolutional neural network was established for quantitative measurement of the
existence and degree of pathology throughout the small intestine, which may
improve computer-aided clinical techniques to assess mucosal atrophy and other
etiologies in real-time with videocapsule endoscopy.
PMID- 28412573
TI - Patient characteristics associated with differences in radiation exposure from
pediatric abdomen-pelvis CT scans: a quantile regression analysis.
AB - BACKGROUND: Computed tomography (CT) is a widely used diagnostic tool in
pediatric medicine. However, due to concerns regarding radiation exposure, it is
essential to identify patient characteristics associated with higher radiation
burden from CT imaging, in order to more effectively target efforts towards dose
reduction. Our objective was to identify the effects of various demographic and
clinical patient characteristics on radiation exposure from single abdomen/pelvis
CT scans in children. METHODS: CT scans performed at our institution between
January 2013 and August 2015 in patients under 16 years of age were processed
using a software tool that estimates patient-specific organ and effective doses
and merges these estimates with data from the electronic health record and
billing record. Quantile regression models at the 50th, 75th, and 90th
percentiles were used to estimate the effects of patients' demographic and
clinical characteristics on effective dose. RESULTS: 2390 abdomen/pelvis CT scans
(median effective dose 1.52mSv) were included. Of all characteristics examined,
only older age, female gender, higher BMI, and whether the scan was a multiphase
exam or an exam that required repeating for movement were significant predictors
of higher effective dose at each quantile examined (all p<0.05). The effects of
obesity and multiphase or repeat scanning on effective dose were magnified in
higher dose scans. CONCLUSIONS: Older age, female gender, obesity, and multiphase
or repeat scanning are all associated with increased effective dose from
abdomen/pelvis CT. Targeted efforts to reduce dose from abdominal CT in these
groups should be undertaken.
PMID- 28412574
TI - Work place drug testing of police officers after THC exposure during large volume
cannabis seizures.
AB - Police officers responsible for the seizure and removal of illegally grown
cannabis plants from indoor and outdoor growing operations face the prospect of
THC exposure while performing their work duties. As a result, a study
investigating the amount of THC on hands and uniforms of officers during raids on
cannabis growing houses (CGHs) and forest cannabis plantations (FCPs) and in the
air at these sites was conducted. Swabs of gloves/hands, chests, and heads/necks
were collected and analysed for THC. Results of hand swabs indicated that
officers removing plants from FCPs were exposed to THC concentrations up to 20
times those involved in raids at CGHs, which was mainly associated with the
number and size of plants seized. Air samples collected inside cannabis houses
showed no detectable THC. Air samples collected inside the cargo area of the
storage trucks used during FCP raids indicated that THC can be volatilised when
lush plants are compressed by other seized plants loaded on top of them in the
truck over a period of several days, allowing composting of plants at the bottom
of the load to commence. The elevated temperature and humidity inside the truck
may assist the decarboxylation of THCA to THC, as well as increasing the rate of
volatilisation of THC. More than 100 urine samples were collected from officers
in raids on both CGHs and FCPs and all tested negative for THC. Removal of
cannabis plants by officers often resulted in cuts, abrasions and ruptured
blisters on exposed skin surfaces, particularly at FCPs. The results in this
study suggest that even when small areas of damaged skin are directly exposed to
THC by contact transfer, the likelihood of showing a positive THC urine test is
low.
PMID- 28412575
TI - The role of illicit, licit, and designer drugs in the traffic in Hungary.
AB - The aim of this study was to investigate the prevalence and pattern of
psychoactive substances among suspected DUID (Driving Under the Influence of
Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252
suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical
illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic
cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in
2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7%
(2015) of all drivers tested, based on the legal criteria of Hungary. Classical
illicit drugs were found to be present in blood or urine of 89-61%, drivers
tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21
28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in
prevalence for classical illicit drugs and a slight but statistically non
significant increase for the other three substance groups. The distribution of
drug types in each category were: [1] classical illicit drugs: cannabis (432),
amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and
clonazepam (36); [3] SDDs: pentedrone (137) and alpha-PVP (33); [4] synthetic
cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit
drug and SDD users was 30 years, while legal medications users were 36 years old
on average, and the mean age of synthetic cannabinoid users was 26.5 years. The
presence of both alcohol and at least one drug in samples was found in about 10%
of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3%
in 2015. Compared to former years the number of drivers who tested positive for
drugs doubled in Hungary, but it is still low compared to alcohol positive cases.
The relatively low detected rate of DUID can be explained by (1) combined alcohol
consumption masking drug symptoms, (2) the absence of road-side tests for illicit
and designer drugs and, (3) police officers not adequately trained to recognize
milder symptoms of impairment. Targeted education of police officers, prompt
medical examination and the use of a symptom-focused on-site survey, could
improve the efficacy of DUID investigations. Our findings are not comparable with
drug consumption habits of the general driving population. The last roadside
survey (DRUID EU-6 Project) was performed in Hungary in 2008-2009, prior to the
mass spreading of designer drugs. As their appearance has drastically changed the
pattern of drug consumption of the population, a new roadside survey, targeting
general drivers, would be necessary.
PMID- 28412576
TI - The occurrence of alcohol/drugs by toxicological examination of selected drivers
in Hong Kong.
AB - The study is to investigate the extent of alcohol/drug(s) use among selected
drivers, i.e. fatally injured drivers from traffic accidents (2006-2015), drink
driving (2006-2015) and drug driving (2010-2015) cases, in Hong Kong. Between
2006 and 2015, specimens from a total of 223 fatally injured drivers were
received for toxicological examination. Except for one driver, all other drivers
with positive findings were male. Alcohol and/or drugs were detected in 60 (27%)
cases where alcohol alone was detected in 40 cases (18%) while drugs with/without
alcohol were detected in 20 cases (9%). A decreasing trend is observed for cases
with blood/breath alcohol concentrations above the prescribed limits in both
fatally injured drivers and drivers from drink driving cases in 2006-2015. Out of
the 20 cases with positive findings in drugs, 8 of them were found with alcohol
in which only one case found at level above the prescribed limit. The frequency
of drugs encountered that are known to affect driving in blood is 31,
representing an average of about 1.7 drugs per individual. Ketamine was the most
frequently detected drug in fatally injured drivers. Sedatives/hypnotics (i.e.
diazepam/nordiazepam, midazolam, 7-aminonimetazepam, 7-aminonitrazepam and
zopiclone), morphine/monoacetylmorphine, cocaine/benzoylecgonine,
methamphetamine, methadone and codeine were also detected. There has been a sharp
increase in the submission of blood/urine specimens for toxicological analysis
related to drug driving cases since 2010 with a total of 48 cases received in
2010-2011. With the introduction of legislative amendment of drug driving law
since 2012, 154 cases were received in 2012-2015. The positive rates for drug
driving cases examined were found to be 90% (43 out of 48 cases) in 2010-2011 and
89% (137 out of 154 cases) in 2012-2015. Drivers with single drug use were more
frequently detected (40 cases in 2010-2011 and 82 cases in 2012-2015) than
multiple drug use (3 cases in 2010-2011 and 55 cases in 2012-2015) but an
increase in the use of more than one drug in driving population is noted.
Ketamine was detected in the majority of cases (34 cases in 2010-2011 and 104
cases in 2012-2015). However, drug driving cases in recent years revealed that
increase usages of methamphetamine, cocaine and zopiclone were observed. The
mean, median and range of ketamine concentrations for 134 blood samples taken
from drivers in drug driving cases were 0.34, 0.27, 0.01-1.8MUg/mL respectively.
PMID- 28412577
TI - Describing heterogeneity of unmet needs among adults with a developmental
disability: An examination of the 2012 Canadian Survey on Disability.
AB - BACKGROUND: As a signatory to the UN Convention on the Rights of Persons with
Disabilities, Canada has committed to protect the rights and dignity of persons
with developmental disabilities (DD), which means that labour markets, education,
and training opportunities should be inclusive and accessible. PURPOSE: Describe
the unmet employment, education and daily needs of adults with DD, with a sub
analysis of persons with autism spectrum disorder (ASD) and cerebral palsy (CP)
in Canada, to inform efficient and equitable policy development. METHODS AND
PROCEDURES: Secondary analysis of 2012 Canadian Survey on Disability was used to
study a sample including working age (15-64 years old) individuals with self
reported DD, CP and ASD. Persons with DD reported on their met and unmet needs in
term of activities of daily living, education and employment. OUTCOMES AND
RESULTS: Labour force participation is the lowest for those with DD compared to
any other disability. Individuals with CP and ASD report a high level of unmet
needs that differ in terms of educational, vocational and daily living supports.
CONCLUSIONS AND IMPLICATIONS: Improving labour force participation to be
inclusive and accessible requires policy that considers the range of unmet needs
that exist for persons with DD.
PMID- 28412578
TI - Communicating with scientific graphics: A descriptive inquiry into non-ideal
normativity.
AB - Scientists' graphical practices have recently become a target of inquiry in the
philosophy of science, and in the cognitive sciences. Here I supplement our
understanding of graphical practices via a case study of how researchers crafted
the graphics for scientific publication in the field of circadian biology. The
case highlights social aspects of graphical production which have gone
understudied - especially concerning the negotiation of publication. I argue that
it also supports a challenge to the claim that empirically-informed "cognitive
design principles" offer an apt understanding of the norms of success which
govern good scientific graphic design to communicate data and hypotheses to other
experts. In this respect, the case-study also illustrates how "descriptive"
studies of scientific practice can connect with normative issues in philosophy of
science, thereby addressing a central concern in recent discussions of practice
oriented philosophy of science.
PMID- 28412579
TI - Equilibrium, thermodynamic and kinetic investigations for biosorption of uranium
with green algae (Cladophora hutchinsiae).
AB - Removal of toxic chemicals from environmental samples with low-cost methods and
materials are very useful approach for especially large-scale applications. Green
algae are highly abundant biomaterials which are employed as useful biosorbents
in many studies. In the present study, an interesting type of green algae,
Cladophora hutchinsiae (C. hutchinsiae) was used for removal of highly toxic
chemical such as uranium. The pH, biosorbent concentration, contact time and
temperature were optimized as 5.0, 12 g/L, 60 min and 20 degrees C,
respectively. For the equilibrium calculations, three well known isotherm models
(Langmuir, Freundlich and Dubinin-Radushkevich) were employed. The maximum
biosorption capacity of the biosorbent was calculated as about 152 mg/g under the
optimum batch conditions. The mean energy of biosorption was calculated as 8.39
kJ/mol from the D-R biosorption isotherm. The thermodynamic and kinetic
characteristics of biosorption were also investigated to explain the nature of
the process. The kinetic data best fits the pseudo-second-order kinetic model
with a regression coefficient of >0.99 for all studied temperatures. The
calculated DeltaH degrees and DeltaG degrees values showed that the biosorption
process is exothermic and spontaneous for temperatures between 293 and 333 K.
Furthermore, after seven cycling process, the sorption and desorption
efficiencies of the biosorbent were found to be 70, and 58%, respectively meaning
that the biosorbent had sufficiently high reusability performance as a clean-up
tool.
PMID- 28412580
TI - A non-toxic dose of cobalt chloride blocks hair cells of the zebrafish lateral
line.
AB - Experiments on the flow-sensitive lateral line system of fishes have provided
important insights into the function and sensory transduction of vertebrate hair
cells. A common experimental approach has been to pharmacologically block lateral
line hair cells and measure how behavior changes. Cobalt chloride (CoCl2) blocks
the lateral line by inhibiting calcium movement through the membrane channels of
hair cells, but high concentrations can be toxic, making it unclear whether
changes in behavior are due to a blocked lateral line or poor health. Here, we
identify a non-toxic treatment of cobalt that completely blocks lateral line hair
cells. We exposed 5-day post fertilization zebrafish larvae to CoCl2
concentrations ranging from 1 to 20 mM for 15 min and measured 1) the spiking
rate of the afferent neurons contacting hair cells and 2) the larvae's health and
long-term survival. Our results show that a 15-min exposure to 5 mM CoCl2
abolishes both spontaneous and evoked afferent firing. This treatment does not
change swimming behavior, and results in >85% survival after 5 days. Weaker
treatments of CoCl2 did not eliminate afferent activity, while stronger
treatments caused close to 50% mortality. Our work provides a guideline for
future zebrafish investigations where physiological confirmation of a blocked
lateral line system is required.
PMID- 28412581
TI - Workplace violence against nurses: A cross-sectional study.
AB - BACKGROUND: Workplace violence is a serious problem for clinical nurses, as it
leads to a series of adverse consequences. However, little information is
available on the prevalence and influencing factors of workplace violence in
China. OBJECTIVES: To determine the prevalence of workplace violence against
Chinese nurses, and its influencing factors. DESIGN: A multi-center, cross
sectional study. SETTINGS: The seven geographical regions (i.e., northeast,
north, central, east, south, northwest, and southwest) of China. PARTICIPANTS:
Four thousand one hundred and twenty-five nurses. METHODS: We randomly selected
28 hospitals, located in 14 cities over 13 provinces across the seven
geographical regions. We distributed 4125 questionnaires between May 4 and
September 23, 2014. The questionnaire included demographic information, the
Workplace Violent Incident Questionnaire, the Jefferson Scale of Empathy-Health
Professionals, and the Practice Environment Scale of Nursing Work Index.
Workplace violence was assessed in terms of physical violence, non-physical
violence, sexual harassment, and organized healthcare disturbances. We then
performed descriptive analyses and logistic regressions on the collected data.
RESULTS: The response rate was 92.97% (n=3835). Additionally, we obtained valid
questionnaires from 3004 individuals. Of these, 25.77% reported experiencing
physical violence, 63.65% non-physical violence, 2.76% sexual harassment, and
11.72% organized healthcare disturbances. A logistic regression analysis revealed
that nurses who have less experience, work a rotating roster, work in emergency
rooms and pediatrics departments, have low empathy levels, and who work in poor
nursing environments have greater odds of experiencing violence. CONCLUSIONS:
Experiences of workplace violence are prevalent among Chinese nurses, and several
complex factors are associated with a greater risk of such violence, including
nurses' personal characteristics, work settings, and work environments. Our
results might help nursing managers understand their employees' work status. We
recommend that nursing leaders provide and enhance education and support for high
risk groups to help protect Chinese nurses from workplace violence.
PMID- 28412582
TI - Sex differences in neural activation following different routes of oxytocin
administration in awake adult rats.
AB - The neuropeptide oxytocin (OT) regulates social behavior in sex-specific ways
across species. OT has promising effects on alleviating social deficits in sex
biased neuropsychiatric disorders. However little is known about potential
sexually dimorphic effects of OT on brain function. Using the rat as a model
organism, we determined whether OT administered centrally or peripherally induces
sex differences in brain activation. Functional magnetic resonance imaging was
used to examine blood oxygen level-dependent (BOLD) signal intensity changes in
the brains of awake rats during the 20min following intracerebroventricular (ICV;
1MUg/5MUl) or intraperitoneal (IP; 0.1mg/kg) OT administration as compared to
baseline. ICV OT induced sex differences in BOLD activation in 26 out of 172
brain regions analyzed, with 20 regions showing a greater volume of activation in
males (most notably the nucleus accumbens and insular cortex), and 6 regions
showing a greater volume of activation in females (including the lateral and
central amygdala). IP OT also elicited sex differences in BOLD activation with a
greater volume of activation in males, but this activation was found in different
and fewer (10) brain regions compared to ICV OT. In conclusion, exogenous OT
modulates neural activation differently in male versus female rats with the
pattern and magnitude, but not the direction, of sex differences depending on the
route of administration. These findings highlight the need to include both sexes
in basic and clinical studies to fully understand the role of OT on brain
function.
PMID- 28412583
TI - Metabolic reprograming of anti-tumor immunity.
AB - Immunotherapies designed to trigger T cell destruction of tumor cells can result
in sustained and complete responses in patients whose cancers were resistant to
available treatment options. Evidence suggests that powering the T cell response
how T cells generate energy - plays an important role in their effectiveness.
Furthermore the metabolism of T cells can be modulated to improve their anti
cancer activities. In this review, we will discuss the key metabolic properties
of anti-cancer T cells, along with potential strategies to enhance immunotherapy
through the modulation of T cell metabolism.
PMID- 28412584
TI - The effects of salt concentration and foulant surface charge on hydrocarbon
fouling of a poly(vinylidene fluoride) microfiltration membrane.
AB - The effects of inorganic salts and organic hydrocarbons on membrane fouling are
often investigated independently. However, in many cases, these foulants are
commonly found together, and such mixtures are rarely the subject of fouling
studies. In this study, crude oil-in-water emulsions were formulated at three
different added NaCl concentrations, 0, 10-3 and 10-1 M. Surface properties, such
as surface tension and surface charge, of these emulsions and a poly(vinylidene
fluoride) (PVDF) microfiltration (MF) membrane were characterized. The Derjaguin
Landau-Verwey-Overbeek (DLVO) model was utilized to simulate membrane-oil droplet
and oil layer-oil droplet surface interactions. The DLVO model qualitatively
predicted increasing fouling propensity with increasing emulsion salt
concentration. The PVDF MF membrane was challenged with crude oil-in-water
emulsions in constant permeate flux crossflow fouling tests to characterize the
fouling propensity of the various emulsions, and the results were consistent with
the model predictions.
PMID- 28412585
TI - The promise of epigenetic therapy: reprogramming the cancer epigenome.
AB - Epigenetics refers to heritable molecular determinants of phenotype independent
of DNA sequence. Epigenetic features include DNA methylation, histone
modifications, non-coding RNAs, and chromatin structure. The epigenetic status of
cells plays a crucial role in determining their differentiation state and proper
function within multicellular organisms. Disruption of these processes is now
understood to be a major contributor to cancer development and progression, and
recent efforts have attempted to pharmacologically reverse such altered
epigenetics. In this mini-review we introduce the concept of epigenetic drivers
of cancer and discuss how aberrant DNA methylation, histone modifications, and
chromatin states are being targeted using drugs either in preclinical, or
clinical development, and how they fit in the context of existing therapies.
PMID- 28412586
TI - Volume-outcome relation in palliative systemic treatment of metastatic
oesophagogastric cancer.
AB - INTRODUCTION: Palliative systemic therapy has been shown to improve survival in
metastatic oesophagogastric cancer. Administration of palliative systemic therapy
in metastatic oesophagogastric cancer varies between hospitals. We aimed to
explore the association between the annual hospital volume of oesophagogastric
cancer patients and survival. METHODS: Patients diagnosed in the Netherlands
between 2005 and 2013 with metastatic oesophagogastric cancer were identified in
the Netherlands Cancer Registry. Patients were attributed according to three
definitions of high volume: (1) high-volume incidence centre, (2) high-volume
treatment centre and (3) high-volume surgical centre. Independent predictors for
administration of palliative chemotherapy were evaluated by means of
multivariable logistic regression analysis, and multivariable Cox proportional
hazard regression analysis was performed to assess the impact of high-volume
centres on survival. RESULTS: Our data set comprised 4078 patients with
metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer,
with a median overall survival of 20 weeks (95% confidence interval [CI] 19-21
weeks) and 16 weeks (95% CI 15-17 weeks), respectively. Patients with oesophageal
cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80,
95% CI 0.70-0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI
0.78-0.99) exhibited a decreased risk of death. For gastric cancer, patients
treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74-0.92) had
a superior outcome. CONCLUSION: Improved survival in patients undergoing
palliative systemic therapy for oesophagogastric cancer was associated with
treatment in high-volume treatment and surgical centres. Further research should
be implemented to explore which specific factors of high-volume centres are
associated with improved outcomes.
PMID- 28412587
TI - Accuracy of the online prognostication tools PREDICT and Adjuvant! for early
stage breast cancer patients younger than 50 years.
AB - IMPORTANCE: Online prognostication tools such as PREDICT and Adjuvant! are
increasingly used in clinical practice by oncologists to inform patients and
guide treatment decisions about adjuvant systemic therapy. However, their
validity for young breast cancer patients is debated. OBJECTIVE: To assess first,
the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality,
and second, its breast cancer-specific mortality estimates, in a large cohort of
breast cancer patients diagnosed <50 years. DESIGN: Hospital-based cohort.
SETTING: General and cancer hospitals. PARTICIPANTS: A consecutive series of 2710
patients without a prior history of cancer, diagnosed between 1990 and 2000 with
unilateral stage I-III breast cancer aged <50 years. MAIN OUTCOME MEASURES:
Calibration and discriminatory accuracy, measured with C-statistics, of estimated
10-year all-cause and breast cancer-specific mortality. RESULTS: Overall,
PREDICT's calibration for all-cause mortality was good (predicted versus
observed) meandifference: -1.1% (95%CI: -3.2%-0.9%; P = 0.28). PREDICT tended to
underestimate all-cause mortality in good prognosis subgroups (range
meandifference: -2.9% to -4.8%), overestimated all-cause mortality in poor
prognosis subgroups (range meandifference: 2.6%-9.4%) and underestimated survival
in patients < 35 by -6.6%. Overall, PREDICT overestimated breast cancer-specific
mortality by 3.2% (95%CI: 0.8%-5.6%; P = 0.007); and also overestimated it
seemingly indiscriminately in numerous subgroups (range meandifference: 3.2%
14.1%). Calibration was poor in the cohort of patients with the lowest and those
with the highest mortality probabilities. Discriminatory accuracy was moderate-to
good for all-cause mortality in PREDICT (0.71 [95%CI: 0.68 to 0.73]), and the
results were similar for breast cancer-specific mortality. Adjuvant!'s
calibration and discriminatory accuracy for both all-cause and breast cancer
specific mortality were in line with PREDICT's findings. CONCLUSIONS: Although
imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality
seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings
were similar. Prognostication tools should be used with caution due to the
intrinsic variability of their estimates, and because the threshold to discuss
adjuvant systemic treatment is low. Thus, seemingly insignificant mortality
overestimations or underestimations of a few percentages can significantly impact
treatment decision-making.
PMID- 28412588
TI - Online self-test identifies women at high familial breast cancer risk in
population-based breast cancer screening without inducing anxiety or distress.
AB - INTRODUCTION: Identifying high familial breast cancer (FBC) risk improves
detection of yet unknown BRCA1/2-mutation carriers, for whom BC risk is both
highly likely and potentially preventable. We assessed whether a new online self
test could identify women at high FBC risk in population-based BC screening
without inducing anxiety or distress. METHODS: After their visit for screening
mammography, women were invited by email to take an online self-test for
identifying highly increased FBC risk-based on Dutch guidelines. Exclusion
criteria were previously diagnosed as increased FBC risk or a personal history of
BC. Anxiety (State-Trait Anxiety Inventory Dutch Version), distress (Hospital
Anxiety Depression Scale) and BC risk perception were assessed using
questionnaires, which were completed immediately before and after taking the
online self-test and 2 weeks later. RESULTS: Of the 562 women invited by email,
406 (72%) completed the online self-test while 304 also completed questionnaires
(response rate 54%). After exclusion criteria, 287 (51%) were included for data
analysis. Median age was 56 years (range 50-74). A high or moderate FBC risk was
identified in 12 (4%) and three (1%) women, respectively. After completion of the
online self-test, anxiety and BC risk perception were decreased while distress
scores remained unchanged. Levels were below clinical relevance. Most women (85%)
would recommend the self-test; few (3%) would not. CONCLUSION: The online self
test identified previously unknown women at high FBC risk (4%), who may carry a
BRCA1/2-mutation, without inducing anxiety or distress. We therefore recommend
offering this self-test to women who attend population-based screening
mammography for the first time.
PMID- 28412589
TI - Emergency admission and survival from aggressive non-Hodgkin lymphoma: A report
from the UK's population-based Haematological Malignancy Research Network.
AB - BACKGROUND: Non-Hodgkin lymphoma (NHL) is often diagnosed after emergency
presentation, a route associated with poor survival and an indicator of
diagnostic delay. Accounting for around half of all NHLs, diffuse large B-cell
lymphoma (DLBCL) is of particular interest since although it is potentially
curable with standardised chemotherapy it can be challenging to identify at an
early stage in the primary care setting. PATIENTS AND METHODS: Set within a socio
demographically representative United Kingdom population of around 4 million
people, data are from an established patient cohort. This report includes all
patients (>=18 years) diagnosed with DLBCL 2004-2011 (n = 1660). Emergency
admissions were identified via linkage to Hospital Episode Statistics using
standard methods, and survival was examined using proportional hazards
regression. RESULTS: Two out of every five patients were diagnosed following an
emergency admission, and this was associated with advanced disease and poor
survival (p < 0.001). Among the 80% of patients treated with curative
chemotherapy, survival discrepancies emerged at the point of diagnosis; the
adjusted hazard ratio (emergency versus non-emergency) at one month being 4.0
(95% confidence interval 1.9-8.2). No lasting impact was evident in patients who
survived for 12 months or more. CONCLUSION: Emergency presentation impacts
negatively on DLBCL survival; patients presenting via this route have
significantly poorer outcomes than patients with similar clinical characteristics
who present via other routes.
PMID- 28412590
TI - Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy
in RAISE, a second-line metastatic colorectal carcinoma phase III trial.
AB - BACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab +
(folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved
overall survival (OS) versus placebo + FOLFIRI for second-line metastatic
colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based
chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73-0.98, P = 0.022). Post hoc
analyses of RAISE patient data examined the association of carcinoembryonic
antigen (CEA) subgroups with efficacy parameters. METHODS: CEA subgroups (<=10
versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The
Kaplan-Meier method estimated the median OS and the progression-free survival
(PFS). Log-rank test compared the survival distributions within the subgroups.
Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup
interaction p-values were calculated by Cox proportional hazards model. RESULTS:
Ramucirumab treatment prolonged survival for the CEA <=10 subgroup (HR = 0.68;
95% CI = 0.50-0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76
1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater
for the CEA <=10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus
0.8 months greater, respectively). The interaction P-value between CEA level and
treatment effect on OS was 0.088. This trend was observed across randomisation
strata and to a lesser extent for PFS (P = 0.594). CONCLUSIONS: Although patients
in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab
treatment, the low baseline CEA level may identify a subgroup of patients with
mCRC who obtain greater benefit from ramucirumab.
PMID- 28412591
TI - Baseline beta-catenin, programmed death-ligand 1 expression and tumour
infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor
treated melanoma patients.
AB - BACKGROUND: The activation of oncogenic Wnt/beta-catenin pathway in melanoma
contributes to a lack of T-cell infiltration. Whether baseline beta-catenin
expression in the context of tumour-infiltrating lymphocytes (TILs) and
programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of
metastatic melanoma patients (MMPs) treated with mitogen-activated protein
kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully
clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and
paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n =
39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of beta
catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein
P3 (FOXP3) expression by immunohistochemistry, and results were correlated with
clinical outcome. Quantitative assessment of mRNA transcripts associated with
Wnt/beta-catenin pathway and immune response was performed in 51 patients.
RESULTS: We found an inverse correlation between tumoural beta-catenin expression
and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the
tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio,
OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of
CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly
associated with a higher probability of response to MAPKi monotherapy. Responding
patients showed a significantly increased expression of mRNA transcripts
associated with adaptive immunity and antigen presentation. By multivariate
analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10
0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006)
were longer in patients with high density of CD8+ T cells and beta-catenin <10%
than those without CD8+ T cells infiltration and beta-catenin >=10%. CONCLUSION:
Our findings provide evidence that in the context of MAPKi monotherapy, immune
subsets in the (TME) and gene signature predict prognosis in MMPs.
PMID- 28412592
TI - Infants' motor simulation of observed actions is modulated by the visibility of
the actor's body.
AB - Previous research suggests that 9-month-old infants will develop a response bias
in the A-not-B search paradigm after only observing an experimenter search for a
hidden object on A-trials. In the current experiment, we tested whether infants
would persist in making errors when only the hands-and-arms of the experimenter
were visible. Three different conditions were included: (1) the experimenter was
silent while hiding and finding the object, (2) the experimenter communicated
with the infant via infant-directed speech, or (3) the body of the experimenter
was visible during the training phase before his head and body were occluded
during the test phase. Unlike previous studies, the results revealed that a
significant proportion of infants searched correctly when the body of the
experimenter was not visible, and only the combination of infant-directed speech
and familiarization with a fully-specified body resulted in a majority of infants
committing search errors. These results are interpreted as suggesting that the
likelihood of infants committing search errors is dependent on their motor
simulation of the experimenter's reaching. The strength of this simulation is
graded by the similarity between the observed action and the motor
representation.
PMID- 28412593
TI - Bootstrapping language acquisition.
AB - The semantic bootstrapping hypothesis proposes that children acquire their native
language through exposure to sentences of the language paired with structured
representations of their meaning, whose component substructures can be associated
with words and syntactic structures used to express these concepts. The child's
task is then to learn a language-specific grammar and lexicon based on (probably
contextually ambiguous, possibly somewhat noisy) pairs of sentences and their
meaning representations (logical forms). Starting from these assumptions, we
develop a Bayesian probabilistic account of semantically bootstrapped first
language acquisition in the child, based on techniques from computational parsing
and interpretation of unrestricted text. Our learner jointly models (a) word
learning: the mapping between components of the given sentential meaning and
lexical words (or phrases) of the language, and (b) syntax learning: the
projection of lexical elements onto sentences by universal construction-free
syntactic rules. Using an incremental learning algorithm, we apply the model to a
dataset of real syntactically complex child-directed utterances and (pseudo)
logical forms, the latter including contextually plausible but irrelevant
distractors. Taking the Eve section of the CHILDES corpus as input, the model
simulates several well-documented phenomena from the developmental literature. In
particular, the model exhibits syntactic bootstrapping effects (in which
previously learned constructions facilitate the learning of novel words), sudden
jumps in learning without explicit parameter setting, acceleration of word
learning (the "vocabulary spurt"), an initial bias favoring the learning of nouns
over verbs, and one-shot learning of words and their meanings. The learner thus
demonstrates how statistical learning over structured representations can provide
a unified account for these seemingly disparate phenomena.
PMID- 28412594
TI - Synthesis and revised stereochemical assignment of C-allyl glucopyranosides and
derivatives.
AB - alpha- and beta-C-allylglucopyranosides and hydroxy-, bromo- and azido
derivatives were prepared through allylation at C-1 of methyl 2,3,4,6-tetra-O
benzyl-D-glucopyranoside or 1-O-acetyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose and
subsequent chemical modifications of the alkene on the anomeric arm. However, we
picked out some discordance between some recent published studies and our
results. After a thorough work of characterization and NMR analysis, we
unambiguously confirmed alpha and beta stereochemistry of the two series of
compounds and fully described for the first time beta-C-propyl alcohol, bromide
and azide of 2,3,4,6-tetra-O-benzyl-D-glucopyranose.
PMID- 28412595
TI - Health-risk behaviour among residents in deprived neighbourhoods compared with
those of the general population in Denmark: A cross-sectional study.
AB - This study compares health-risk behaviours (including the co-occurrence of health
risk behaviours) of residents in the deprived neighbourhoods with those of the
general population of Denmark. It also examines associations between
sociodemographic and socioeconomic characteristics and health-risk behaviours in
deprived neighbourhoods in Denmark. Even after adjustment for socioeconomic
characteristics there were large differences in health-risk behaviours between
residents in deprived neighbourhoods and the general population. In the deprived
neighbourhoods large sociodemographic and socioeconomic differences in health
risk behaviours were found among the residents. Our findings highlight the need
for health promotion programmes targeting residents in deprived neighbourhoods.
PMID- 28412596
TI - Is lenticulostriated vasculopathy an unfavorable prognostic finding in infants
with congenital cytomegalovirus infection?
AB - BACKGROUND: Lenticulostriated vasculopathy (LSV) detected in head ultrasound
(HUS) has been related to neurological and hearing sequelae in infants with
congenital cytomegalovirus (cCMV) infection. OBJECTIVE: To assess the role of LSV
in predicting neurodevelopmental and hearing outcomes in infants with cCMV
infection. STUDY DESIGN: We enrolled consecutive infants who were affected by
cCMV infection and underwent HUS within the first month of life. Data on clinical
onset and course, laboratory findings, visual/hearing functions and
neurodevelopmental outcome were collected. As controls, infants with suspected
intrauterine exposure to Toxoplasma and with no confirmed congenital
toxoplasmosis were considered. RESULTS: Data from 161 infants with cCMV infection
(105 symptomatic) and 133 controls were analyzed. HUS was normal in 66 (41%) cCMV
patients. Among these, 28 (42.4%) were symptomatic and 38 (57.6%) asymptomatic
infants. The percentage of patients with no HUS abnormalities was higher in
asymptomatic (38/56, 67.9%) than in symptomatic infants (28/105, 26.7%) (p<0.05).
LSV, as isolated or associated with other brain abnormalities, was diagnosed in
64/161 (39.7%) patients with cCMV compared to 24/133 (18%) controls (p<0.05). In
cCMV group, LSV was found in 51 (48.6%) symptomatic infants and in 13 (72.2%)
asymptomatic patients (p>0.05). Overall, in the whole population of 95 patients
with cCMV and abnormal HUS results, LSV (alone or with other findings) did not
represent a risk factor for unfavorable neurological and hearing outcome. Similar
results were obtained when we limited the analysis to the group of symptomatic
cCMV patients. CONCLUSIONS: Although LSV is a common HUS finding in infants with
cCMV infection, its presence is not predictive of an adverse outcome. Our data
suggest that HUS as a single neuroimaging investigation is unreliable in
selecting candidates to antiviral therapy, mainly in presence of LSV as isolated
finding.
PMID- 28412597
TI - Peptide blockers of Kv1.3 channels in T cells as therapeutics for autoimmune
disease.
AB - The voltage-gated Kv1.3 channel in T lymphocytes is a validated therapeutic
target for diverse autoimmune diseases. Here we review the discovery of Kv1.3,
its physiological role in T cells, and why it is an attractive target for
modulating autoimmune responses. We focus on peptide inhibitors because the first
Kv1.3-selective inhibitor in human trials is a peptide derived from a marine
organism. Two broad classes of peptides block Kv1.3, the first from scorpions and
the second from sea anemones. We describe their structures, their binding site in
the external vestibule of Kv1.3, how they have been engineered to improve Kv1.3
specificity, and their pharmacokinetic and pharmacodynamic properties. Finally,
we highlight the therapeutic potential of Kv1.3 peptide inhibitors to treat
autoimmune diseases without compromising protective immune responses.
PMID- 28412598
TI - Effect of two isolated vocal facilitating techniques glottal fry and yawn-sigh on
the phonation of female speech-language pathology students: A pilot study.
AB - OBJECTIVE: The purpose of this study was to determine the effect of two isolated
vocal facilitating techniques, glottal fry and yawn-sigh, on the phonation of
vocally healthy female speech-language pathology (SLP) students. STUDY DESIGN: A
multigroup pretest-posttest design was used. METHODS: A group of thirty-six
healthy female SLP students with a mean age of 18.1 years were assigned into
three groups: a glottal fry group (practicing the facilitating technique glottal
fry across 18 weeks, n=12), a yawn-sigh group (practicing the facilitating
technique yawn-sigh across 18 weeks, n=12) and a control group (receiving no
facilitating techniques, n=12). To compare vocal measures before and after this
training period, an identical objective voice assessment protocol (maximum
performance task, acoustic analysis, voice range profile and Dysphonia Severity
Index) was performed in the three groups. Groups were compared over time using
linear mixed models. Within-group effects of time were determined using post hoc
pairwise comparisons. RESULTS: Glottal fry resulted in a significant decrease in
lowest and highest intensity. Yawn-sigh resulted in a significant increase in
fundamental frequency, a significant decrease in shimmer and noise-to-harmonic
ratio, and a significant increase in highest intensity. CONCLUSIONS: Yawn-sigh
may have a positive effect on the phonation of female vocally healthy future
SLPs, whereas results are less supportive for using glottal fry in training this
population's voice.
PMID- 28412599
TI - Group intervention for individuals with primary progressive aphasia and their
spouses: Who comes first?
AB - Primary progressive aphasia (PPA) is a neurodegenerative dementia in which
language impairment is the first and most dominant symptom. There is a
considerable dearth of interventions for PPA although language rehabilitation has
made headway in managing the disorder. Thus far, no comprehensive services have
been proposed for PPA clients and/or their spouses. This paper describes the
first structured group intervention program designated exclusively for people
with PPA and their caregivers. This pilot project originates from a clinical
service and presents supporting evidence for initiation of a larger study to
establish an evidence-based intervention for PPA. A 10-week intervention program
comprised working on language activities, learning communication strategies,
counselling and education. Outcome measures administered to participants and
their spouses before and after the intervention were compared showed improvements
in quality of communication and coping skills in the PPA group compared to
controls. Qualitative comments from all 10 participants in the active treatment
group highlighted the necessity of intervention that is tailored specifically to
the PPA population and addresses the needs of both individuals with PPA and their
caregivers. All participants in the intervention group contributed to the study
and are also co-authors of this paper.
PMID- 28412600
TI - DNA methylation changes at TREM2 intron 1 and TREM2 mRNA expression in patients
with Alzheimer's disease.
AB - OBJECTIVES: Recent genome-wide association studies revealed that Triggering
receptor expressed on myeloid cells 2 (TREM2) was associated with Alzheimer's
disease (AD) and other neurodegenerative diseases. We previously reported that
TREM2 mRNA is highly expressed in leukocytes of AD patients compared to those in
healthy controls. However, the mechanism of TREM2 expression change is still not
known. In this study, we examined the involvement of the DNA methylation status
of TREM2 in its high gene expression. MATERIALS AND METHODS: Fifty AD subjects
and age- and sex-matched control subjects were recruited (25 males, 25 females;
79.9 +/- 5.27 and 79.4 +/- 3.92 years old, respectively). TREM2 mRNA expression
and the percentage of DNA methylation at four CpG sites in intron 1 of TREM2 were
studied using their peripheral leukocytes. RESULTS: We confirmed that TREM2 mRNA
expression in leukocytes was significantly higher in AD patients than in controls
(p = 0.007). The percentage methylation at three CpG sites in TREM2 intron 1 was
significantly lower in AD subjects than in control: CpG1, 9.4 +/- 3.2 vs 11.9 +/-
4.0 (p = 0.001); CpG2, 15.4 +/- 4.9 vs 19.1 +/- 4.8 (p = 0.001); CpG3, 20.8 +/-
5.5 vs 25.5 +/- 5.4 (p < 0.001); and the average percentage methylation of all
CpG sites: 13.5 +/- 3.7 vs 16.1 +/- 3.8 (p = 0.002), respectively. In addition,
there were significant negative correlations between TREM2 mRNA expression and
the percentage DNA methylation of each of CpG sites (CpG1, r = -0.416, p < 0.001;
CpG2, r = -0.510, p < 0.001; CpG3, r = -0.504, p < 0.001; CpG4, r = -0.356, p <
0.001). CONCLUSIONS: Lower DNA methylation at TREM2 intron 1 caused higher TREM2
mRNA expression in the leukocytes of AD subjects versus controls and may be a
biomarker for AD.
PMID- 28412601
TI - A systematic review of factors associated with service user satisfaction with
psychiatric inpatient services.
AB - BACKGROUND: Satisfaction is seen as an indicator of the quality of mental health
services and has been related to outcomes and compliance with treatment. The
current review seeks to examine the factors relating to satisfaction with
inpatient services. METHOD: A search was conducted of PsycInfo, Web of Science,
Cinahl, Embase and Medline databases. Screening resulted in 32 papers being
included in the review. Papers were subject to quality assessment using the Mixed
Methods Appraisal Tool (MMAT). RESULTS: Review of the included papers suggested
factors relating to satisfaction could be broadly classified as either service
user or service/ward related. Service user related factors included findings that
satisfaction was higher when service users were admitted voluntarily. Service
related factors included findings that satisfaction was negatively associated
with experiences of coercion and positively associated with being on an open
ward. CONCLUSION: It appears that coercion has a key role in ratings of
satisfaction. Additionally, service users reported an impact of staff
relationships, and the ward environment. Satisfaction is associated with a range
of factors, an awareness of which will allow for the development of quality
services that meet the needs of service users.
PMID- 28412602
TI - Secondary outcomes from the pediatric obsessive compulsive disorder treatment
study II.
AB - : The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II)
investigated the benefit of serotonin reuptake inhibitor (SRI) augmentation with
cognitive behavioral therapy (CBT). Primary outcomes focused on OCD symptom
change and indicated benefit associated with a full course of CBT. Given that the
majority of youth with OCD suffer from significant comorbid symptoms and impaired
quality of life, the current study examined POTS II data for effects on secondary
outcomes. Participants were 124 youth ages 7-17 years with a primary diagnosis of
OCD who were partial responders to an adequate SRI trial. Participants were
randomized to medication management, medication management plus instructions in
cognitive behavioral therapy (CBT), or medication management plus full CBT. Acute
effects on non-OCD anxiety, depression, inattention, hyperactivity, and quality
of life were examined across treatment conditions. Improvement across treatment
was observed for non-OCD anxiety, inattention, hyperactivity, and quality of
life. Changes were generally significantly greater in the group receiving full
CBT. Child-rated depression was not found to change. OCD-focused treatment lead
to improvement in other areas of psychopathology and functioning. For youth who
are partial responders to SRI monotherapy, augmentation with full CBT may yield
the greatest benefit on these secondary outcomes. CLINICAL TRIALS REGISTRATION:
Treatment of Pediatric OCD for SRI Partial Responders, Clinicaltrials.gov
Identifier: NCT00074815, http://clinicaltrials.gov/show/NCT00074815.
PMID- 28412603
TI - Impairments of balance, stepping reactions and gait in people with cervical
dystonia.
AB - BACKGROUND: Impaired balance is common in neurological disorders. Cervical
dystonia is a neurological movement disorder affecting the neck. The effect of
this aberrant head posture on physical function is unknown. OBJECTIVES: To
compare balance, mobility, gait and stepping reactions between ten people with
cervical dystonia and ten control adults. METHODS: Spatiotemporal gait parameters
and walking speed were assessed using a computerised walkway. Step length and
time, time in double support and gait variability were calculated, then
normalised to gait speed. Centre of pressure path length was assessed with eyes
open and eyes closed to calculate a Romberg Quotient. Simple and choice reaction
times were measured using customised apparatus while mobility was assessed by the
timed up and go. Cervical spine range of motion was measured using a head mounted
goniometer. Self-reported scales included Falls Self Efficacy Scale and Dystonia
Discomfort Scale. RESULTS: There was a difference between groups for most outcome
measures. The timed up-and-go and walking speed was slower (both P<0.005) and the
Romberg Quotient lower (P=0.046) in cervical dystonia. People with cervical
dystonia had lower falls self-efficacy (P=0.0002). Reduced cervical range of
motion was correlated with balance, stepping reaction time and mobility (all
P<0.05). Timed up and go was positively associated with stepping reaction time
(P<0.01). Dystonia discomfort did not impact function. CONCLUSIONS: People with
cervical dystonia displayed deficits in balance, gait and stepping reactions, and
expressed higher fear of falling. Studies to further elucidate functional
limitations and their impact on activity and participation in daily life are
required.
PMID- 28412604
TI - Highlighting the differential role of leaf paraheliotropism in two Mediterranean
Cistus species under drought stress and well-watered conditions.
AB - The differential degree by which paraheliotropism may counterbalance the
deleterious impact of high irradiance between congeneric species in relation to
different water availabilities has been poorly investigated. We followed the
evolution of gas exchange, quenching analysis and OJIP parameters in restrained
(R) and free (F) to move leaves of Cistus monspeliensis (CM) and Cistus
salvifolius (CS) under drought stress (WS) and well-watered conditions (WW).
Concerning gas exchange parameters, leaf restriction effect was overall not
significant in CM except in apparent carboxylation efficiency (Ce) under WS,
while CS showed a significant sensitivity of maximum net photosynthetic rate
(Amax), stomatal conductance (gs) and Ce even under WW. The recovery analysis
highlighted also a faster gs recovery in F leaves. Furthermore, in both the
species, restriction affected photon allocation pathways especially in terms of
light-regulated and light-independent constitutive non-photochemical energy
dissipation under WW, ultimately affecting electron transport rate (ETR).
Nevertheless, the OJIP analysis provided us evidences that CM was characterized
by a down-regulation of ETR while an impairment occurs in CS. In CM this was due
to its ability to modify a certain fraction of reaction centers thus resulting in
a higher capability for dissipation of excess light energy under well-watered
conditions, not affecting electron transport efficiency. This response was not
observed in CS. Overall, we demonstrated that congeneric species, even mostly
sharing the same physiological targets, differ in the degree by which leaf
movements help to counterbalance the negative effect of the high irradiance in
relation with the amount of water available.
PMID- 28412605
TI - Brachytic 1 of barley (Hordeum vulgare L.) encodes the alpha subunit of
heterotrimeric G protein.
AB - Physiological and molecular biological analysis of the dwarf barley (Hordeum
vulgare L.) mutant brachytic 1 (brh1) was conducted. The root responses of brh1
to brassinolide were weaker than those of wild type, but the responses of leaf
segments of dark-grown plants were not. Responses of brh1 to gibberellin A3 were
similar to or slightly stronger than those of wild type. Endogenous levels of
these hormones in young seedlings were not clearly different between brh1 and
wild type. Skotomorphogeneses of brh1 were similar to those of wild type. Some of
these physiological characteristics of brh1 resemble those of the dwarf rice
(Oryza sativa L.) mutant daikoku (dwarf1; d1), whose dwarfism is caused by a
mutation in the heterotrimeric G protein alpha (Galpha) subunit. A database
search indicated that the barley Galpha gene is located near the locus where Brh1
has already been genetically mapped. Sequences of the Galpha gene and cDNAs of
five brh1 alleles contained substitutions and a deletion that lead to the
production of abnormal Galpha proteins. These results indicate that the phenotype
of brh1, similarly to that of d1, is caused by mutations in an orthologous gene
encoding Galpha.
PMID- 28412606
TI - Quantification of alprenolol and propranolol in human plasma using a two
dimensional liquid chromatography (2D-LC).
AB - A new two-dimensional liquid chromatography (2D-LC) method using a column
switching valve, with a restricted-access media (RAM) column in the first
dimension was developed and validated for the quantification of two beta-blockers
in human plasma. Several parameters, such as sample collection, mobile phase
composition and flow rate for sample cleanup, transference and analytical
separation of the beta-blockers were investigated and optimized. The developed
method allowed for the simultaneous pre-treatment and quantification of
alprenolol (ALP) and propranolol (PRO) in human plasma in less than 25min. The
method consisted in the injection of 100MUL of plasma samples on the RAM alkyl
diol-silica column (Lichrospher(r) RP-18 ADS, 25MUm) with water/acetonitrile
(98:2, v/v; at a flow rate of 2.0mL/min) and then transferred (via a six-port
valve) to the analytical column (Luna PFP (2), 150*4.6mm ID, 100A, 3MUm) with
0.1% (v/v) triethylamine in water acidified with trifluoroacetic acid
(pH=3)/acetonitrile (74:26, v/v) at a flow rate of 0.6mL/min in a back-flush
mode. The column oven temperature was optimized to 42 degrees C and the
fluorescence detector set at 280nm and 310nm (excitation and emission,
respectively). The method was validated according to the European Medicines
Agency's guidelines and was linear (r2>0.999) over a dynamic range of 5.0 -
200ng/mL. Recoveries ranged from 90.2 and 107% and the lower limit of
quantification was 5.0ng/mL for both compounds. Precision was expressed as a
percentage of relative standard deviation and did not exceed 11%. Finally, the
method was successfully applied to determine the plasma concentration of PRO in
four healthy volunteers.
PMID- 28412607
TI - Effect of early postnatal exposure to valproate on neurobehavioral development
and regional BDNF expression in two strains of mice.
AB - Valproate has been used for over 30years as a first-line treatment for epilepsy.
In recent years, prenatal exposure to valproate has been associated with
teratogenic effects, limiting its use in women that are pregnant or of
childbearing age. However, despite its potential detrimental effects on
development, valproate continues to be prescribed at high rates in pediatric
populations in some countries. Animal models allow us to test hypotheses
regarding the potential effects of postnatal valproate exposure on
neurobehavioral development, as well as identify potential mechanisms mediating
observed effects. Here, we tested the effect of early postnatal (P4-P11)
valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in
two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early
valproate exposure on regional BDNF protein levels, a potential target of
valproate, and mediator of neurodevelopmental outcomes. We found that early life
valproate exposure led to significant motor impairments in both SVE129 and
C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as
well as impairments in the righting reflex (P7-8), wire hang (P17), open field
(P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early
locomotor effects were strain- and dose-dependent. We observed no effects of
valproate on early markers of anxiety-like behavior. Importantly, early life
valproate exposure had significant effects on regional BDNF expression, leading
to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice,
while not impacting hippocampal BDNF protein levels. These observations indicate
that postnatal exposure to valproate may have significant, and region-specific
effects, on neural and behavioral development, with specific consequences for
cerebellar development and motor function.
PMID- 28412609
TI - Dexamethasone promotes regeneration of crushed inferior alveolar nerve by
inhibiting NF-kappaB activation in adult rats.
AB - PURPOSE: Nuclear factor kappa B (NF-kappaB), which is closely related to
inflammation, has become a topic of interest for research. The aim of this study
is to investigate the effects of dexamethasone (Dex), an inhibitor of NF-kappaB,
on inferior alveolar nerve injury in adult rats. MATERIALS AND METHODS: The
crushed inferior alveolar model is established in Wistar rats and they are
randomly divided into three groups according to treatment: pyrrolidine
dithiocarbamate (PDTC), dexamethasone (Dex), and saline (physiological saline).
After treatment, the rats are respectively sacrificed at 3, 7, and 14d, and
inferior alveolar nerves are extracted for histochemical and western blot
analysis. RESULT: Compared with the PDTC and saline groups, nerve fibers in the
Dex group are regularly arranged with few vacuoles, which is similar to normal
inferior alveolar nerves. Immunofluorescent results show significantly decreased
NF-kappaB expression in the Dex group. Western bolt shows higher expression of
GAP-43 and lower expression of NF-kappaB. CONCLUSION: Taken together, all results
show that dexamethasone significantly improved the regeneration of crushed
inferior alveolar nerves by inhibiting NF-kappaB activation in adult rats.
PMID- 28412608
TI - DSM-5 criteria for PTSD in parents of pediatric patients with epilepsy: What are
the changes with respect to DSM-IV-TR?
AB - Increasing literature suggests the need to explore for post-traumatic stress
disorder (PTSD) and post-traumatic stress symptoms in parents and caregivers of
children with acute and chronic illnesses but scant data are available on
epilepsy. The aim of the present study was to estimate full and partial PTSD
rates among parents of children with epilepsy comparing DSM-5 and DSM-IV-TR
criteria. Further, the aim of the present study was to examine possible gender
differences between mothers and fathers. Results showed 9.1% and 12.1% PTSD rates
in the total sample, according to DSM-5 or DSM-IV-TR criteria, respectively, with
an overall consistency of 92.9% (Kohen's K=0.628, p=.453). Significant gender
differences emerged for Avoidance/Numbing and Hyperarousal symptoms diagnosed by
means of DSM-IV-TR criteria, as well as for Negative alterations in
cognitions/mood and Hyperarousal symptoms, when adopting DSM-5 criteria. This
study underscores the relevance of detecting PTSD in parents of children with a
chronic illness such as epilepsy.
PMID- 28412610
TI - Overexpression and varied clinical significance of Th9 versus Th17 cells in
distinct subtypes of oral lichen planus.
AB - OBJECTIVE: Oral lichen planus (OLP) presents with large numbers of T lymphocytes
accumulating beneath the epithelium of the oral mucosa; however, its aetiology
remains obscure. A potential role for an emerging novel T cell subset, Th9, in
OLP has recently been suggested but remains to be clarified. The current aim was
to investigate the expression and potential clinical significance of Th9 cells in
distinct subtypes of OLP. MATERIALS AND METHODS: Peripheral blood samples were
collected from 41 OLP patients and 18 healthy controls (HCs). Flow cytometric
analysis was used to detect the CD4+ T helper subset Th9 (IL-9+IL-17-CD4+ Th
cells) and Th17 (IL-9-IL-17+CD4+ Th cells) expression levels. RESULTS: Flow
cytometry results showed significantly elevated levels of Th9 cells in reticular
and erosive OLP compared to HCs. Th9 expression in erosive OLP was less than in
reticular OLP, indicating that Th9 but not Th17 cells may play a predominant role
in reticular disease. However, in erosive OLP patients, we found much higher
levels of Th17 cells compared to reticular OLP patients and HCs, indicating that
Th17 dominates in erosive OLP. Statistical analysis showed positive correlations
of Th9 cells and Th17 cells in patients with reticular or erosive OLP but none in
HCs. CONCLUSIONS: Th9 and Th17 cells may take the predominant roles in reticular
and erosive OLP respectively, and their numbers were positively correlated in
reticular and erosive OLP patients. Elevated circulating Th9 cells may help
maintain immune balance in OLP immunopathogenesis, which requires further
investigation.
PMID- 28412611
TI - Hypermethylation of Death-Associated Protein Kinase (DAPK1) and its association
with oral carcinogenesis - An experimental and meta-analysis study.
AB - OBJECTIVES: The value of abnormal DNA methylation of DAPK1 promoter and its
association with various cancers have been suggested in the literature. To
establish the significance of DNA methylation of DAPK1 promoter in oral squamous
cell carcinoma (OSCC), we a) performed a case-control study, b) evaluated
published data for its utility in the diagnosis and prognosis of OSCC and c)
identified the association of DAPK1 gene expression with promoter DNA methylation
status. DESIGN: Bisulfite gene sequencing of DAPK1 promoter region was performed
on non-malignant and malignant oral samples. Further, using a systematic search,
330 publications were retrieved from PubMed, Scopus, and Google Scholar and 11
relevant articles were identified. RESULTS: Significant association of DAPK1
promoter methylation with OSCC (p<0.0001) was observed in the case-control study.
The studies chosen for meta-analysis showed prognostic and predictive
significance of DAPK1 gene promoter, despite defined inconsistencies in few
studies. Overall, we obtained a statistically significant (p-value<0.001)
association for both sensitivity and specificity of DAPK1 DNA promoter
methylation in oral cancer cases, without publication bias. CONCLUSION: DNA
hypermethylation of DAPK1 gene promoter is a promising biomarker for OSCC
prediction/prognostics and suggests further validation in large distinct cohorts
to facilitate translation to clinics.
PMID- 28412612
TI - Impairment in Social Functioning differentiates youth meeting Ultra-High Risk for
psychosis criteria from other mental health help-seekers: A validation of the
Italian version of the Global Functioning: Social and Global Functioning: Role
scales.
AB - Social and occupational impairments are present in the schizophrenia prodrome,
and poor social functioning predicts transition to psychosis in Ultra-High Risk
(UHR) individuals. We aimed to: 1) validate the Italian version of the Global
Functioning: Social (GF: S) and Global Functioning: Role (GF: S) scales; 2)
evaluate their association with UHR criteria. Participants were 12-21-years-old
(age, mean=15.2, standard deviation=2.1, male/female ratio=117/120) nonpsychotic
help-seekers, meeting (N=39) or not (N=198) UHR criteria. Inter-rater reliability
was excellent for both scales, which also showed good to excellent concurrent
validity, as measured by correlation with Global Assessment of Functioning (GAF)
scores. Furthermore, GF:S and GF: R were able to discriminate between UHRs and
non-UHRs, with UHRs having lower current scores. After adjusting for current GAF
scores, only current GF:S scores independently differentiated UHR from non-UHR
(OR=1.33, 95%CI: 1.02-1.75, p=0.033). Finally, UHR participants showed a steeper
decrease from highest GF:S and GF: R scores in the past year to their respective
current scores, but not from highest past year GAF scores to current scores.
GF:S/GS: R scores were not affected by age or sex. GF:S/GF: R are useful
functional level and outcome measures, having the advantage over the GAF to not
confound functioning with symptom severity. Additionally, the GF:S may be helpful
in identifying UHR individuals.
PMID- 28412613
TI - Intensified emotion perception in depression: Differences in physiological
arousal and subjective perceptions.
AB - People suffering from depression perceive themselves and their surroundings as
more negative than healthy ones. An explanation might be that depressed
individuals experience negative information as more stressful than non-depressed
subjects and, consequently, respond in an amplified manner on a subjective and
physiological level. To test this proposition, we presented 41 patients with
recurrent depressive episodes and 42 controls with stimuli from the International
Affective Picture System split into three valence categories while different
parameters of physiological arousal (e.g., heart rate variability) and subjective
perceptions of valence and arousal were assessed. Furthermore, we examined social
skills and emotional competence. Results regarding physiological arousal revealed
an elevated skin temperature and a more accentuated respiratory frequency in
depressed subjects. Furthermore, depressed subjects rated the stimuli as more
negative and arousing, which was associated with reduced social and emotional
competence. Variation in antidepressant medication, menstrual cycle and other
factors that have an impact on HRV are a potential bias. Our findings suggest an
intensified perception of negative emotion in depressed individuals as compared
to controls that manifests itself in an increased physiological arousal as well
as on a subjective level. This intensified emotion perception is further
associated with deficits in social and emotional competence.
PMID- 28412614
TI - Pain and multiple facets of anger and hostility in a sample seeking treatment for
problematic anger.
AB - A number of studies have reported associations between pain and anger in samples
with chronic pain, but research has mostly overlooked associations between pain
and anger in those with problematic anger. The present study explored
associations between pain severity and a variety of anger and hostility
constructs in a sample seeking anger treatment (n =131). Zero-order correlations
and partial correlations were used to examine associations between pain, anger,
and hostility, controlling for depressive symptoms. Hierarchical regression
models examined potential interaction effects of gender on associations between
pain and these outcomes. Pain severity was positively associated with trait
anger, outward anger expression, hostile interpretation bias, hostile ideation,
and inability to forgive others. These associations were independent of co
occurring depressive symptoms, with some exceptions. Gender moderated the
association between pain and hostile ideation such that pain was positively
associated with hostile ideation in women but not men. Pain severity was uniquely
associated with multiple outcomes of relevance to individuals undergoing
treatment for problematic anger. Clinical implications will be discussed.
PMID- 28412615
TI - Suicide risk among young children after the Great East Japan Earthquake: A follow
up study.
AB - On 11 March 2011, the Great East Japan Earthquake and subsequent tsunami hit East
Japan. We aim to investigate the impact of trauma experiences related to the
earthquake on suicide risk among young children, stratified by child sex.
Participants at baseline were children who were exposed to the 2011 disaster at
preschool age (affected area, n=198; unaffected area, n=82, total n=280). From
July 2013 to May 2014, suicide risk was assessed using the Mini International
Neuropsychiatric Interview for Children and Adolescents (MINI-KID) in a follow-up
interview conducted by a child psychiatrist or psychologist (N=210, follow-up
rate: 75%). Among young girls in the affected area, 12 out of 65 (18.5%) showed
suicidal ideation, which is significantly higher than girls in the unaffected
area (4.7%, p for chi-square=0.036). In the multivariate model adjusted for
potential confounders and mediators, the odds ratio for 4 or more trauma
experiences related to the earthquake was 5.74 (95% confidence interval: 0.83
39.6, p=0.076) compared to no trauma experience related to the earthquake. Among
young boys, trauma exposure was not associated with suicidal ideation. Our
findings showed that young girls who experienced earthquake-related trauma at
preschool age had a higher suicidal ideation 3 years after the earthquake.
PMID- 28412616
TI - Measuring fluctuations across the Continuum of Auditory Hallucinations.
Development and validation of a state inventory.
AB - In order to identify causes and triggers of hallucinations that can inform
therapy, reliable, valid, and change-sensitive instruments to assess
hallucinatory experiences in the subclinical and clinical range are needed. We
developed and validated a novel scale, the Continuum of Auditory Hallucinations -
State Assessment (CAHSA), to be used for repeated assessment of the subclinical
factors vivid imagination, intrusive thoughts, and perceptual sensitivity as well
as auditory hallucinations. After selecting items for the four factors in a first
test sample (n=84), we tested factorial validity using CFA and criterion validity
with self-reported psychosis-like experiences (n=534). Finally, within-subject
variation of CAHSA scores over 14 days and time-lagged associations between its
factors were explored (n=85). A 9-item CAHSA was selected that showed good
factorial validity, criterion validity, and substantial, valid within-subject
variation. Time-lagged regression showed that vivid imagination, perceptual
sensitivity, and intrusive thought precede auditory hallucinations. In sum, the
CAHSA validly measures fluctuation along the continuum of auditory
hallucinations, is sensitive to change, and well suited for experimental studies,
repeated measurement, and longitudinal research.
PMID- 28412617
TI - Selection of optimized air pollutant filtration technologies for petrochemical
industries through multiple-attribute decision-making.
AB - Selecting cost-effective and efficient air filtration technologies that ensure
sustainable development is a challenge to national, regional and local policy
makers. Various factors such as efficiency, maintainability, and design of the
developed devices can affect the selection of optimized technologies. The present
study aimed to select optimal technologies for air filtration devices in
petrochemical industries through a multi-criteria decision-making (MADM) method
based on a fuzzy model of Technique for Order of Preference by Similarity to
Ideal Solution (TOPSIS). Five criteria (filtration efficiency, cost,
maintainability, designability, and size) were used to rank air pollution control
technologies designed to eliminate particulate matter (PM), volatile organic
compounds (VOCs), and ammonia (NH3). According to the results, the research
criteria had different weights for different air pollutants. High-efficiency
particulate air (HEPA + pre collector) filters, plasma chemistry, and chemical
absorption were identified as the most appropriate filtration methods for PM,
VOCs, and NH3, respectively (coefficients = 0.923, 0.9586, and 0.867,
respectively).
PMID- 28412618
TI - Untapped potentials of acrylonitrile-butadiene-styrene/polyurethane (ABS/PU)
blend membrane to purify dye wastewater.
AB - Production of acrylonitrile-butadiene-styrene/polyurethane (ABS/PU) blend
membrane with high rejection efficiency for disperse and vat dyes, is introduced
as a facile and cost effective technique to purify textile wastewater. In this
respect, membranes are produced using commercially available polymers, i.e. ABS
and PU, with different compositions (ABS/PU: 100/0, 80/20, 70/30, 60/40 and 50/50
w/w) through wet casting. Casting solutions with concentration of 30 wt% are
prepared using two different solvents, i.e. dimethylformamide (DMF) and N-methyl
2- pyrrolidone (NMP). The prepared membranes are characterized using a variety of
analytical techniques including SEM imaging, FTIR spectroscopy, dry and wet gas
permeation, evaluation of reusability, antifouling and mechanical properties,
photostability, surface hydrophilicity and pure water permeability (PWP) of the
produced membranes. According to the results, irrespective of solvent type,
ABS/PU membranes with higher PU content have lower porosity and smaller pore size
both of which contribute to enhanced dye rejection efficiency. This is while the
impact of PU content on the photostability of ABS/PU membranes was found to be
negligible. Additionally, the produced ABS/PU membranes exhibit good reusability
and antifouling properties. However, the mechanical properties of ABS/PU
membranes with higher PU contents are inferior to those with lower PU contents.
This contrast highlights the prominence of optimum PU content to make a trade-off
between dye rejection efficiency and mechanical properties. In this regard,
ABS/PU (60/40 w/w) membrane is recognized as the one with optimum composition.
Furthermore, it was found that regardless of PU content, membranes cast from DMF
based solutions exhibit superior rejection performance over those cast from NMP
based solutions. Overall, one can witness that employing ABS/PU membranes
provides a meritorious and clean approach to refine disperse and vat dye
wastewaters, a great threat to the environment and human health.
PMID- 28412619
TI - Denitrification potential in the subsurface environment in the Manawatu River
catchment, New Zealand: Indications from oxidation-reduction conditions,
hydrogeological factors, and implications for nutrient management.
AB - A sound understanding of the effects of hydrogeological factors on loss,
transport and transformation of farm nutrients is essential for predicting their
impacts on ecosystem health of receiving waters. We assessed the potential of
groundwater to attenuate nitrate through denitrification, and the distribution of
this potential across the Tararua Groundwater Management Zone (GWMZ) in the
Manawatu River catchment, New Zealand. We combined a number of methods in an
unprecedented manner to confirm findings and obtain supporting evidence for the
features that determine the subsurface denitrification characteristics. Our
results showed that the denitrification characteristics of groundwater varied
considerably in the Tararua GWMZ. The southern part of the Tararua GWMZ contained
mainly oxic groundwater with low potential to denitrify, whereas the middle and
northern parts of the Tararua GWMZ contained reduced groundwater with high
denitrification potential. The hydrogeological features that influence
denitrification potential in groundwater were identified as soil texture and
drainage class, and the aquifer material or rock type. Low dissolved oxygen
levels and nitrate concentrations were found in groundwater where the
combinations of soil and rock types had poor drainage characteristics as opposed
to higher concentrations in groundwater under well-drained soils and rocks (e.g.
gravels). Intensive pastoral farming over well-drained soils and rocks showed
high nitrate concentration in groundwater. This spatial variability in
denitrification potential of groundwater offers a targeted management of
nutrients runoff and leaching from pastoral lands to reduce their impacts on
receiving surface waters.
PMID- 28412620
TI - Adsorption of organic stormwater pollutants onto activated carbon from sewage
sludge.
AB - Adsorption filters have the potential to retain suspended pollutants physically,
as well as attracting and chemically attaching dissolved compounds onto the
adsorbent. This study investigated the adsorption of eight hydrophobic organic
compounds (HOCs) frequently detected in stormwater - including four polycyclic
aromatic hydrocarbons (PAHs), two phthalates and two alkylphenols - onto
activated carbon produced from domestic sewage sludge. Adsorption was studied
using batch tests. Kinetic studies indicated that bulk adsorption of HOCs
occurred within 10 min. Sludge-based activated carbon (SBAC) was as efficient as
tested commercial carbons for adsorbing HOCs; adsorption capacities ranged from
70 to 2800 MUg/g (Cinitial = 10-300 MUg/L; 15 mg SBAC in 150 mL solution; 24 h
contact time) for each HOC. In the batch tests, the adsorption capacity was
generally negatively correlated to the compounds' hydrophobicity (log Kow) and
positively associated with decreasing molecule size, suggesting that molecular
sieving limited adsorption. However, in repeated adsorption tests, where
competition between HOCs was more likely to occur, adsorbed pollutant loads
exhibited strong positive correlation with log Kow. Sewage sludge as a carbon
source for activated carbon has great potential as a sustainable alternative for
sludge waste management practices and production of a high-capacity adsorption
material.
PMID- 28412621
TI - Xanthium strumarium L. seed hull as a zero cost alternative for Rhodamine B dye
removal.
AB - Treatment of polluted water has been considered as one of the most important
aspects in environmental sciences. Present study explores the decolorization
potential of a low cost natural adsorbent Xanthium strumarium L. seed hull for
the adsorption of a toxic xanthene dye, Rhodamine B (RHB). The characterization
of the adsorbent revealed the presence of high amount of carbon, when exposed to
Electron Dispersive Spectroscopy (EDS). Further appreciable decolorization took
place which was confirmed by Fourier Transform Infrared Spectroscopy (FTIR)
analysis noticing shift in peaks. Isothermal studies indicated multilayer
adsorption following Freundlich isotherm. The rate of adsorption was supported by
second order kinetics directing a chemical phenomenon during the process with
dominance of film diffusion as the rate governing step. Moreover paper aims at
correlating the chemical arena to the mathematical aspect providing an in-depth
information of the studied treatment process. For proper assessment and
validation of the observed data, experimental data has been statistically treated
by applying different error functions namely, Chi-square test (chi2), Sum of
absolute errors (EABS) and Normalized standard deviation (NSD). Further practical
applicability of the low cost adsorbent was evaluated by continuous column mode
studies with 72.2% of dye recovery. Xanthium strumarium L. proved to be
environment friendly low cost natural adsorbent for decolorizing RHB from aquatic
system.
PMID- 28412622
TI - Population-production-pollution nexus based air pollution management model for
alleviating the atmospheric crisis in Beijing, China.
AB - In recent years, increscent emissions in the city of Beijing due to expanded
population, accelerated industrialization and inter-regional pollutant
transportation have led to hazardous atmospheric pollution issues. Although a
number of anthropogenic control measures have been put into use, frequent/severe
haze events have still challenged regional governments. In this study, a hybrid
population-production-pollution nexus model (PPP) is proposed for air pollution
management and air quality planning (AMP) with the aim to coordinate human
activities and environmental protection. A fuzzy-stochastic mixed quadratic
programming method (FSQ) is developed and introduced into a PPP for tackling
atmospheric pollution issues with uncertainties. Based on the contribution of an
index of population-production-pollution, a hybrid PPP-based AMP model that
considers employment structure, industrial layout pattern, production mode,
pollutant purification efficiency and a pollution mitigation scheme have been
applied in Beijing. Results of the adjustment of employment structure, pollution
mitigation scheme, and green gross domestic product under various environmental
regulation scenarios are obtained and analyzed. This study can facilitate the
identification of optimized policies for alleviating population-production
emission conflict in the study region, as well as ameliorating the hazardous air
pollution crisis at an urban level.
PMID- 28412623
TI - The urban heat island effect, its causes, and mitigation, with reference to the
thermal properties of asphalt concrete.
AB - The Urban Heat Island (UHI) is a phenomenon that affects many millions of people
worldwide. The higher temperatures experienced in urban areas compared to the
surrounding countryside has enormous consequences for the health and wellbeing of
people living in cities. The increased use of manmade materials and increased
anthropogenic heat production are the main causes of the UHI. This has led to the
understanding that increased urbanisation is the primary cause of the urban heat
island. The UHI effect also leads to increased energy needs that further
contribute to the heating of our urban landscape, and the associated
environmental and public health consequences. Pavements and roofs dominate the
urban surface exposed to solar irradiation. This review article outlines the
contribution that pavements make to the UHI effect and analyses localized and
citywide mitigation strategies against the UHI. Asphalt Concrete (AC) is one of
the most common pavement surfacing materials and is a significant contributor to
the UHI. Densely graded AC has low albedo and high volumetric heat capacity,
which results in surface temperatures reaching upwards of 60 degrees C on hot
summer days. Cooling the surface of a pavement by utilizing cool pavements has
been a consistent theme in recent literature. Cool pavements can be reflective or
evaporative. However, the urban geometry and local atmospheric conditions should
dictate whether or not these mitigation strategies should be used. Otherwise both
of these pavements can actually increase the UHI effect. Increasing the
prevalence of green spaces through the installation of street trees, city parks
and rooftop gardens has consistently demonstrated a reduction in the UHI effect.
Green spaces also increase the cooling effect derived from water and wind
sources. This literature review demonstrates that UHI mitigation techniques are
best used in combination with each other. As a result of the study, it was
concluded that the current mitigation measures need development to make them
relevant to various climates and throughout the year. There are also many
possible sources of future study, and alternative measures for mitigation have
been described, thereby providing scope for future research and development
following this review.
PMID- 28412624
TI - Effects of 1,25-dihydroxyvitamin D3 in an ovalbumin-induced allergic rhinitis
model.
AB - IL-17-producing Th17 cells play an important role in allergic airway diseases,
but their local expression and regulation in allergic rhinitis (AR) is not well
understood. This study investigated the effects of 1,25-dihydroxyvitamin D3 (1,25
(OH)2D3) on T-bet expression, Th1 cells, Th2 cells, Th17 cells and IL-33-positive
epithelial cells in AR. C57BL/6 mice were intranasally sensitized and challenged
with ovalbumin (OVA), and 1,25-(OH)2D3 was intraperitoneally injected into AR
mice. Cytokine levels were measured with enzyme-linked immunosorbent assays,
phenotypic analysis of Th1, Th2 and Th17 cells in the spleen was completed with
flow cytometry, and the CD4+IL-17+ cells in the Nasopharynx-associated lymphoid
tissue (NALT) and IL-33-positive cells in nasal mucosa was evaluated with
immunofluorescence microscopy. AR mice shown significantly increased Th2 and Th17
cell ratio in spleen, IL-17 level in serum, IL-5 and IL-13 levels in NALF but a
lower number of IL-33-positive epithelial cells and Th1 response (Th1 and
Tbet+Th1 cell ratio in the spleen and serum IFN-gamma level) than the control
mice.1,25-(OH)2D3 treatment significantly decreased the number of sneezing, nasal
rubbing, OVA-sIgE and IL-17 in serum, IL-5 and IL-13 levels in NALF, Th17 cell
ratio in the spleen and the histological of nasal mucosal but increased the
number of IL-33-positive epithelial cells in AR mice. However, 1,25-(OH)2D3
treatment did not significantly influence IFN-gamma level in serum, and Th1,
Tbet+Th1 and Th2 cell ratio in spleen. Thus, 1,25-(OH)2D3 may exert anti-allergic
effects by suppressing Th17 responses and local production of IL-5 and IL-13
cytokines.
PMID- 28412625
TI - Toxicity of two effluents from agricultural activity: Comparing the genotoxicity
of sugar cane and orange vinasse.
AB - Vinasse, produced by several countries as a by-product of agricultural activity,
has different alternatives for its reuse, mainly fertirrigation. Several
monocultures, such as sugar cane and orange crops, produce this effluent. Sugar
cane vinasse is already widely used in fertirrigation and orange vinasse has
potential for this intention. However, its use as a fertilizer has caused great
concern. Thus, ecotoxicological evaluation is extremely important in order to
assess the possible effects on the environment. Therefore, the aim of this study
was to evaluate the potential toxicity of vinasse of two different crops: sugar
cane and orange. For this purpose, bioassays with Allium cepa as a test organism
were performed with two vinasse dilutions (2.5% and 5%) to detect chromosomal
aberrations and micronucleus induction. The results showed that both types of
vinasse are able to induce chromosomal aberrations in meristematic cells, mainly
nuclear and anaphasic bridges, suggesting genotoxic potential. The induction of
micronuclei in cells of the F1 region suggests that the two residues have
mutagenic potential. Thus, caution is advised when applying these effluents in
the environment.
PMID- 28412626
TI - Quantification of heat shock protein 70 and acetylcholinesterase over a time
course suggests environmental adaptation in a foundational molluscan species.
AB - Waterways in urban areas often act as repositories for sewage, industrial waste,
and environmental contaminants. In response, inhabitants of these watersheds
undergo physiological adaptations specific to their respective environments.
Effects of these stressors can be assayed by quantification of various well
documented biomarkers in sentinel species such as the Atlantic Ribbed mussel,
Geukensia demissa, a native to the Bronx River Estuary, Bronx, NY, USA. Heat
shock protein 70 (Hsp70) is a universally expressed biomarker for an array of
environmental stressors including toxins and low dissolved oxygen. To better
understand the mechanisms by which organisms tolerate their contaminated
environments, we monitored the constitutive and heat shock-induced levels of two
proteins: Hsp70 and acetylcholinesterase (AChE) in natural populations of G.
demissa from differentially impacted sites: the Bronx River and Greenwich Cove
estuaries. We show that G. demissa from the Bronx River exhibits a higher level
of constitutive Hsp70, and launches a more rapid and robust heat shock response
than does its Greenwich Cove counterpart. In addition, AChE levels are recovered
more quickly in Bronx River mussels. Based on response pattern investigations
from heat stress as well as constitutive expression, we suggest that the
Hsp70/AChE chaperone/client relationship exemplifies the unique adaptive
mechanisms utilized by organisms in order to tolerate environmentally impacted
habitats. Results from this study offer important insights from an ecological
perspective into the molecular and cellular basis of stress response and provide
valuable information regarding adaptation to the increased demands of challenging
environments.
PMID- 28412627
TI - Exploratory factor analysis of fluoride removal efficiency associated with the
chemical properties of geomaterials.
AB - This study explored the chemical properties of geomaterials in relation with
their fluoride removal efficiencies from water under acidic conditions. Two types
each of as-received and engineered steel slags were tested, and their F- removal
efficiencies were compared with those of other common or commercially available
acid spill response materials. The chemical properties of the geomaterials were
analyzed by x-ray photoelectron spectroscopy to determine their surface elemental
compositions and by Brunauer-Emmett-Teller analysis to determine their surface
areas. The F- removal efficiencies were calculated based on the fluoride
concentrations in the remaining solutions using an ion chromatography technique.
A principal component analysis (PCA) was conducted to identify the dominant
independent variables that influenced the F- removal efficiencies, revealing that
the surface area was most closely correlated with the F- removal efficiency. A
microscopic analysis of the geomaterials, conducted using an energy dispersion
spectrometer technique after the F- sorption reaction had occurred revealed that
the local Al, Si, or O concentration was an important latent independent variable
for the F- removal efficiency. These variables had been hidden in the PCA
results. Therefore, aluminosilicate-rich geomaterials with a high surface area
offer primary candidates as effective sorbents for fluoride in water under acidic
conditions.
PMID- 28412628
TI - 4-nitroso-sulfamethoxazole generation in soil under denitrifying conditions:
Field observations versus laboratory results.
AB - The formation of 4-nitroso-sulfamethoxazole and 4-nitro-SMX, two transformation
products (TPs) of sulfamethoxazole (SMX) was investigated under batch soil slurry
experiments and in a field study. Due to their low occurrence levels (ng/L) in
environmental waters, a suitable analytical method based on liquid chromatography
- high resolution - mass spectrometry was developed. Consequently, field
observations revealed, for the first time, the occurrence of 4-nitroso-SMX in
groundwater at concentrations as high as 18ng/L.Nitric oxide (NO) steady-state
concentrations were determined in soil slurry experiments because this reactive
specie accounted for the formation of 4-nitroso-SMX and 4-nitro-SMX. Measurements
revealed that environmental SMX concentrations (0.2-2MUg/L) at neutral pH induced
the accumulation of nitric oxide. Under acidic conditions (pH<6), nitrous acid
(HONO) was the major source of nitric oxide while under neutral/basic conditions
nitric oxide release was related to the inhibition of denitrification processes.
Under laboratory experiments, SMX nitration reaction appeared to be an
irreversible transformation pathway, while 4-nitroso-SMX was slowly transformed
over time. The occurrence of 4-nitroso-SMX conditions was therefore unexpected in
the field study but could be due to its continuous input from soil and/or its
relative persistence under anoxic conditions. A mechanism for 4-nitroso-SMX
formation was proposed involving a nitrosative desamination pathway through a
phenyl radical.
PMID- 28412629
TI - Toxicological interactions of ibuprofen and triclosan on biological activity of
activated sludge.
AB - The growing use of pharmaceutical and personal care products increases their
concentrations in the wastewater entering treatment plants and their levels into
biological reactors. The most extended biological wastewater treatment is the
activated sludge process. The toxicity of ibuprofen and triclosan, individually
and combined, was studied by tracking the biological activity of the activated
sludge measuring oxygen uptake rate and the inhibition of the esterase activity.
Short-term exposure produced significant inhibition in oxygen uptake, with lower
damage to enzymatic activity. Median effect values for oxygen uptake inhibition
were 64+/-13mgL-1 and 0.32+/-0.07mgL-1 for ibuprofen and triclosan respectively
using 125mgL-1 activated sludge. For the inhibition of enzymatic activity values
were 633+/-63mgL-1 for ibuprofen and 1.94+/-0.32mgL-1 for triclosan. Results
indicated that oxygen uptake, related to primary activity of microorganisms, was
more strongly affected than the enzymatic activity associated to energy
consumption. Toxicity interactions were determined using the Combination Index
isobologram method. Results showed antagonism at lower values of affected
population, after which the mixtures tended to additivity and synergism. For the
case of enzymatic activity, the antagonism was less marked and the additivity
range was higher.
PMID- 28412630
TI - Phenol remediation by peroxidase from an invasive mesquite: Turning an
environmental wound into wisdom.
AB - The present study examines mesquite (Prosopis juliflora), an invasive species, to
yield peroxidase that may reduce hazards of phenolics to living organisms. As low
as 0.3U of low-purity mesquite peroxidase (MPx) efficiently remove phenol and
chlorophenols (90-92%) compared with Horseradish peroxidase (HRP) (40-60%). MPx
shows a very high removal efficiency (40-50%) at a wide range of pH (2-9) and
temperature (20-80 degrees C), as opposed to HRP (15-20%). At a high-level of the
substrate (2.4mM) and without the addition of PEG, MPx maintains a significant
phenolic removal (60->=92%) and residual activity (~25%). It proves the
superiority of MPx over HRP, which showed insignificant removal (10-12%) under
similar conditions, and no residual activity even with PEG addition. The root
elongation and plant growth bioassays confirm phenolic detoxification by MPx.
Readily availability of mesquite across the countries and easy preparation of MPx
from leaves make this tree as a sustainable source for a low-technological
solution for phenol remediation. This study is the first step towards converting
a biological wound of invasive species into wisdom and strength for protecting
the environment from phenol pollution.
PMID- 28412631
TI - Effectiveness of Physiotherapy interventions plus Extrinsic Feedback for neck
disorders: A systematic review with meta-analysis.
AB - PURPOSE: To systematically review the effectiveness of Physiotherapy
interventions combined with extrinsic feedback (EF) compared to Physiotherapy
interventions alone or control for the management of neck pain and disability.
METHODS: Randomized clinical trials were searched and retrieved from six
databases, from inception through August 2016. Risk of bias of included studies
was assessed using the PEDro scale. When possible data were pooled and Meta
analyses were conducted. The quality and strength of evidence for each outcome
was assessed using the GRADE approach. RESULTS: Eight studies (n = 677) were
included in the review. The pooled estimates suggested Physiotherapy intervention
+ EF was not superior to Physiotherapy intervention alone for disability (MD =
0.38; 95%CI = -0.91 to 0.18; I2 = 82%), but was superior for pain (MD = -0.37;
95%CI = -0.73 to -0.01; I2 = 68%). Physiotherapy intervention + EF was not
superior than control for disability scores (SMD = -3.94; 95%CI = -12.06 to 4.18;
I2 = 92%). Physiotherapy intervention + EF intervention was more effective than
control for pain scores at short-term (SMD = -1.44; 95%CI = -2.25 to-0.63; I2 =
50%). Most studies did not specify nor use the ideal characteristics of EF.
CONCLUSION: There is very low quality of evidence that Physiotherapy intervention
+ EF is more effective than Physiotherapy intervention alone or control for short
term pain, but not for disability. Physiotherapy intervention plus EF was more
effective than Physiotherapy alone for acute neck pain, but not for chronic pain
or disability. There was high risk of bias within included studies. Future
studies are likely to change the estimates of the effects of Physiotherapy
intervention plus EF on neck rehabilitation.
PMID- 28412632
TI - Seed dormancy and germination of the medicinal holoparasitic plant Cistanche
deserticola from the cold desert of northwest China.
AB - Cistanche deserticola is a holoparasitic plant with high medicinal value that
reproduces only by seeds. However, the requirements for seed dormancy break and
germination of this species remain unclear. The freshly matured dust-like seeds
consist of a water-permeable seed coat and an undifferentiated oval-shaped embryo
embedded in endosperm. No fresh seeds germinated in water or a 10-5 M fluridone
solution at any incubation temperature within 60 days. Length of embryos in seeds
incubated in warm- and cold-started stratification sequences had increased 10.4
and 11.7% after 50 and 40 weeks, respectively. After 6 months, length of embryos
in seeds stratified at 5 degrees C had increased by 12%. Germination of fresh
seeds and of seeds stratified at 5 degrees C for 6 months and then incubated in
mixed fluridone/gibberellic acid 3 (GA3) solutions at 30/20 degrees C germinated
to only 2.6 and 11.7%, respectively. Embryos of fresh seeds and of cold
stratified seeds had increased 29.4 and 15.8% in length, respectively, at the
time of germination, but they never differentiated into organs. The highest
germination (54.4%) was for seeds incubated in a 10-5 M solution of fluridone in
darkness in spring that had overwinter on the soil surface in the natural
habitat. Our study indicates that breaking of physiological dormancy (PD) occurs
first and then the embryo grows to a critical length (0.44 mm) without
differentiation into organs prior to seed germination. Seeds for which PD had
been broken were induced to germinate by fluridone and GA3 at high temperature.
Taken together, these results suggest that C. deserticola seeds have a
specialized kind of morphophysiological dormancy. This study reveals possible
ways to release seed dormancy that will be useful in propagating this medicinal
species.
PMID- 28412633
TI - Relationship among color development, anthocyanin and pigment-related gene
expression in 'Crimson Seedless' grapes treated with abscisic acid and sucrose.
AB - 'Crimson Seedless' is one of the most important table grape varieties in Chile,
but under certain environmental conditions, the fruit exhibits inadequate red
color development, causing economic losses due to lower product quality. The use
of plant growth regulators, such as abscisic acid (ABA) and ethylene, during
development increases the anthocyanin content of the skin, improving the color of
the berry. Recently, sucrose has been identified as a signaling molecule capable
of regulating the expression of genes of the anthocyanin biosynthesis pathway.
The aim of this study was to analyze the effect of application of ABA and/or
sucrose on color development and their relationship with anthocyanin metabolism.
Applications of ABA (400 ppm or 200 ppm) and/or sucrose (90 mM) were performed
close to the veraison stage. During development and at harvest, quality
attributes such as berry firmness, total soluble solids and titratable acidity
were not affected by these treatments. Increased red color development was
observed in fruits treated with ABA and/or sucrose, due to accumulation of
anthocyanins. Fruits subjected to sucrose treatment showed higher levels of
anthocyanins than untreated fruits but lower levels than fruits treated with ABA.
Increased expression of genes involved in anthocyanin biosynthesis was observed
in ABA- and sucrose-treated fruits compared to untreated fruits. Based on these
findings, we demonstrated that sucrose improved fruit color development by
increasing synthesis and accumulation of anthocyanins, thus allowing earlier
harvests and improving table grape quality.
PMID- 28412634
TI - Chitosan-induced immunity in Camellia sinensis (L.) O. Kuntze against blister
blight disease is mediated by nitric-oxide.
AB - Blister blight disease, caused by an obligate biotrophic fungal pathogen,
Exobasidium vexans Massee is posing a serious threat for tea cultivation in Asia.
As the use of chemical pesticides on tea leaves substantially increases the toxic
risks of tea consumption, serious attempts are being made to control such
pathogens by boosting the intrinsic natural defense responses against invading
pathogens in tea plants. In this study, the nature and durability of resistance
offered by chitosan and the possible mechanism of chitosan-induced defense
induction in Camellia sinensis (L.) O. Kuntze plants against blister blight
disease were investigated. Foliar application of 0.01% chitosan solution at 15
days interval not only reduced the blister blight incidence for two seasons, but
also maintained the induced expressions of different defense related enzymes and
total phenol content compared to the control. Defense responses induced by
chitosan were found to be down regulated under nitric oxide (NO) deficient
conditions in vivo, indicating that the observed chitosan-induced resistance is
probably activated via NO signaling. Such role of NO in host defense response was
further established by application of the NO donor, sodium nitroprusside (SNP),
which produced similar defense responses accomplished through chitosan treatment.
Taken together, our results suggest that increased production of NO in chitosan
treated tea plants may play a critical role in triggering the innate defense
responses effective against plant pathogens, including that causing the blister
blight disease.
PMID- 28412635
TI - Particle manipulations in non-Newtonian microfluidics: A review.
AB - Microfluidic devices have been widely used since 1990s for diverse manipulations
of particles (a general term of beads, cells, vesicles, drops, etc.) in a variety
of applications. Compared to the active manipulation via an externally imposed
force field, the passive manipulation of particles exploits the flow-induced
intrinsic lift and/or drag to control particle motion with several advantages.
Along this direction, inertial microfluidics has received tremendous interest in
the past decade due to its capability to handle a large volume of samples at a
high throughput. This inertial lift-based approach in Newtonian fluids, however,
becomes ineffective and even fails for small particles and/or at low flow rates.
Recent studies have demonstrated the potential of elastic lift in non-Newtonian
fluids for manipulating particles with a much smaller size and over a much wider
range of flow rates. The aim of this article is to provide an overview of the
various passive manipulations, including focusing, separation, washing and
stretching, of particles that have thus far been demonstrated in non-Newtonian
microfluidics.
PMID- 28412636
TI - Facile size-controlled preparation of highly photocatalytically active ZnCr2O4
and ZnCr2O4/Ag nanostructures for removal of organic contaminants.
AB - The ZnCr2O4 nanoparticles were synthesized and characterized by different
techniques such as; XRD, SEM, EDS, VSM, TEM and IR. In order to modify the
morphology of structures, various alkaline and capping agents were used. For this
work TETA, en and NH3 as alkaline agents and salicylaldehyde, N,N'
(bis(salicylidene)-ethylene-1,2-diamine) and SDS as capping agents were employed.
The cubic morphology for the ZnCr2O4 nanoparticles were obtained by using TETA
and N,N'-(bis(salicylidene)-ethylene-1,2-diamine). When SDS and TETA were used,
very uniform spherical zinc chromite nanoparticles with fine grain size were
produced. Then on the surface of these nanoparticles, Ag nanoparticles were
covered by photodeposition method. For investigation photocatalytic activity of
the nanoparticles, several factors such as various azo dyes, temperature, grain
size and morphology were investigated. Also by using of ZnCr2O4/Ag nanoparticles
prepared polymer based nanocomposite. Results indicate that, nanoparticles can
enhance the thermal stability of the PVA matrix.
PMID- 28412637
TI - Photoimmobilization of zwitterionic polymers on surfaces to reduce cell adhesion.
AB - Simple and robust methods for modifying hydrophobic polymer surfaces with
zwitterionic polymers using UV irradiation were developed. Two random
zwitterionic copolymers consisting of either carboxybetaine or sulfobetaine
methacrylamide monomers and monomers bearing a photolabile azidophenyl group were
directly photoimmobilized on polymeric surfaces (polyester, polyethylene and
polystyrene) via covalent interactions in a spatially controlled manner. These
copolymers were also electrospun to form self-standing mats. The modified
surfaces were characterized by X-ray photoelectron spectroscopy, atomic force
microscopy, infrared spectroscopy and contact angle measurements. The
electrospinning method involved the use of a trifluoroethanol solution with a
copolymer concentration in the range from 2 to 10wt.%. BHK 21 cell adhesion to
both modified surfaces and mats was dramatically reduced compared to unmodified
surfaces.
PMID- 28412638
TI - Influence of ionic liquid on pseudocapacitance performance of electrochemically
synthesized conductive polymer: Electrochemical and theoretical investigation.
AB - This study demonstrates a method for improving supercapacitive performance of
electrochemically synthesized conductive polymer. In this regards, 1-Butyl-3
methyl imidazolium hexafluorophosphate (BI) as a new high efficient ionic liquid
was synthesized using chemical approach and then fabricated POAP/BI films by
electro-polymerization of POAP in the presence of BI to serve as the active
electrode for electrochemical supercapacitor. Theoretical study (AIM) and
electrochemical analysis have been used for characterization of ionic liquid and
POAP/BI composite film. Different electrochemical methods including galvanostatic
charge-discharge experiments, cyclic voltammetry and electrochemical impedance
spectroscopy are carried out in order to investigate the performance of the
system. This work introduces new most efficient materials for electrochemical
redox capacitors with advantages including ease synthesis, high active surface
area and stability in an aqueous electrolyte.
PMID- 28412639
TI - Aggregation of thermoresponsive core-shell nanoparticles: Influence of particle
concentration, dispersant molecular weight and grafting.
AB - Thermoresponsive core-shell nanoparticles represent an interesting class of
materials with a triggered solubility transition. However, depending on the
system, their aggregation behavior above the lower critical solution temperature
(LCST) is ambiguous and obviously linked to a multitude of parameters. The
induced aggregation of a set of well characterized poly(N-isopropylacrylamide)
nitrodopamine grafted superparamagnetic iron oxide nanoparticles is investigated
with respect to the PNIPAM molecular weight (5-30kDa) and concentration using
differential scanning calorimetry and temperature-cycled dynamic light scattering
measurements. PNIPAM molecular weight clearly influences the thermoresponsiveness
of the material, including LCST, colloidal aggregation and deaggregation as well
as transition enthalpy. Furthermore, a strong impact of topology (grafted vs.
free polymer chain) on the thermoresponsiveness is observed. Cluster size above
the LCST depends on concentration and PNIPAM molecular weight. This makes it
reasonable to conduct aggregation experiments under constant (high) particle
molar concentration for comparative studies. Similarly, low particle molar
concentration is used to elucidate individual particle shell properties by
avoiding masking inter-particle effects.
PMID- 28412640
TI - Is a hilly neighborhood environment associated with diabetes mellitus among older
people? Results from the JAGES 2010 study.
AB - BACKGROUND: Although living in a hilly environment may promote muscular activity
in the daily lives of residents, and such activity may prevent diabetes mellitus,
few studies have focused on the impact of living in a hilly environment on
diabetes mellitus. The purpose of this study was to investigate the impact of a
hilly neighborhood environment on DM in older people. METHODS: We used data from
the Japan Gerontological Evaluation Study, a population-based, cross-sectional
study of individuals aged 65 or older without long-term care needs in Japan,
which was conducted in 2010. A total of 8904 participants in 46 neighborhoods had
responded to the questionnaire and undergone a health check. Diabetes mellitus
was diagnosed as HbA1c >= 6.5% and those undergoing treatment for diabetes
mellitus. Poorly controlled diabetes mellitus was diagnosed in those without
other chronic diseases who had an HbA1c > 7.5%, and in those with other chronic
diseases if their HbA1c was >8.0%. Neighborhood environment was evaluated based
on the percentage of positive responses in the questionnaire and geographical
information system data. A multilevel analysis was performed, adjusted for
individual-level risk factors. Furthermore, sensitivity analysis was conducted
for those who were undergoing treatment for diabetes mellitus (n = 1007).
RESULTS: After adjustment for other physical environmental and individual
covariates, a 1 interquartile range increase (1.48 degrees ) in slope in the
neighborhood decreased the risk of poorly controlled diabetes mellitus by 18%
(odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.70-0.97). Sensitivity
analysis confirmed that larger slopes in the neighborhood showed a significant
protective effect against diabetes mellitus among those who were undergoing
treatment for diabetes mellitus (OR: 0.73, 95% CI: 0.59-0.90). CONCLUSION: A
hilly neighborhood environment was not associated with diabetes mellitus, but was
protective against poorly controlled diabetes mellitus.
PMID- 28412641
TI - The gap between entitlement and access to healthcare: An analysis of "candidacy"
in the help-seeking trajectories of asylum seekers in Montreal.
AB - In 2012 the Canadian government made significant cuts to its historically strong
federal refugee health coverage plan. While this policy had negligible effects on
the level of coverage provided to asylum seekers in Quebec, there is evidence
that this group nonetheless experienced reduced healthcare access during the
period of polarized national debate that ensued. This study engaged the
"candidacy" model of healthcare access to illuminate factors contributing to the
observed gap between entitlement and access. Twenty-five semi-structured
interviews were conducted with asylum seekers in Montreal to elicit narrative
accounts of difficulties encountered in the pursuit of healthcare. Thematic
content analysis in conjunction with a holistic examination of help-seeking
trajectories revealed several important barriers to obtaining care, including
widespread confusion and misinformation about refugee health coverage, cumbersome
administrative procedures specific to asylum seekers, and long wait times.
Feelings of marginalization and insecurity associated with precarious migratory
status appeared to amplify the effects of these barriers to care such that even a
minor access difficulty could have dramatic effects on future help-seeking and
access outcomes. Demonstrating awareness of public discourses interrogating their
deservingness of health coverage, participants often interpreted access
difficulties as evidence of health professionals' unwillingness to serve them.
Such interpretations conspired with fears associated with the asylum claim
process to suppress self-advocacy, further help-seeking, and at times even
information-seeking. This finding is particularly significant in that it suggests
a mechanism through which hostile public representations of forced migrants
increasingly prevalent in Western host countries-can themselves endanger the
physical, psychological, and social health of highly disadvantaged populations,
even in the presence of strong entitlement policies. We close with reflections on
how theoretical models of healthcare access might be adjusted to better
accommodate the unique experiences of precarious status migrants.
PMID- 28412642
TI - Impact of duration of hypotension prior to norepinephrine initiation in medical
intensive care unit patients with septic shock: A prospective observational
study.
AB - PURPOSE: To determine the impact of duration of hypotension prior to
norepinephrine initiation on outcomes in MICU patients with septic shock. We
hypothesized increased duration of hypotension prior to norepinephrine initiation
would be associated with an increased risk for ICU mortality. MATERIALS AND
METHODS: We conducted a prospective-observational study in the MICU of a single
center tertiary academic medical center. We enrolled 160 adults >=18years old
with septic shock. Descriptive statistics were computed for demographic and
outcome variables. Primary logistic regression analysis was adjusted for severity
of illness. RESULTS: The mean age of our patients was 59years (+/-17); 42% were
female; the mean APACHE II score was 24.1 (+/-8.0), and the mean SOFA score was
9.6 (+/-4.0). Median duration of hypotension prior to norepinephrine initiation
was 3.6h (IQR 1.6-9.9). Duration of hypotension prior to norepinephrine did not
increase the risk for ICU mortality (OR 1.03 per hour after hypotension, 95% CI:
0.98-1.09, p=0.20). CONCLUSION: Duration of hypotension less than one hour and
greater than one hour prior to norepinephrine initiation in MICU patients with
septic shock is not associated with an increased risk for ICU mortality.
PMID- 28412643
TI - My action lasts longer: Potential link between subjective time and agency during
voluntary action.
AB - Time perception distorts across different phases of bodily movement. During motor
execution, sensory feedback matching an internal sensorimotor prediction is
perceived to last longer. The sensorimotor prediction also underlies sense of
agency. We investigated association between subjective time and agency during
voluntary action. Participants performed hand action while watching a video
feedback of their hand with various delays to manipulate agency. The perceived
duration and agency over the video feedback were judged. Minimal delay of the
video feedback resulted in longer perceived duration than the actual duration and
stronger agency, while substantial feedback delay resulted in shorter perceived
duration and weaker agency. These fluctuations of perceived duration and agency
were nullified by the feedback of other's hand instead of their own, but not by
inverted feedback from a third-person perspective. Subjective time during action
might be associated with agency stemming from sensorimotor prediction, and self
other distinction based on bodily appearance.
PMID- 28412644
TI - An association of health behaviors with depression and metabolic risks: Data from
2007 to 2014 U.S. National Health and Nutrition Examination Survey.
AB - BACKGROUND: Both depression and metabolic syndrome (MetS) confer an increased
risk of developing type 2 diabetes (T2D) and cardiovascular disease. Accumulating
evidence suggests healthy behaviors are crucial to maintain, improve and manage
chronical disease and mental health; and unhealthy diet and sedentary behavior
were found two major risk factors of MetS. The objective of this study was to
investigate whether health behaviors (alcohol consumption, smoking, diet and
recreational physical activity) are associated with depression and metabolic
syndrome simultaneously. METHODS: This study included 1300 participants aged 20
years and over who had answered mental health-depression screener questions (PHQ
9) and finished examinations and laboratory tests related to five risk factors of
MetS during the U.S. National Health and Nutrition Examination Survey (NHANES)
2007-2014. A set of series of weighted logistic regression models were used to
investigate the aforementioned relationship. RESULTS: The prevalence of
depression among U.S. adults is 15.08%. The two most often reported depression
symptoms were "Trouble sleeping or sleeping too much" and "Feeling tired or
having little energy", with rates of14.68% and 13.09%, respectively. Participants
who engaged in only light physical activity were more likely to have been
identified as experiencing depression and MetS than those who engaged in vigorous
physical activity with odd ratios 3.18 (95% CI: 1.59, 6.37) and 3.50 (95%CI:
2.17, 5.63), respectively. Individuals in the study having poor diets were more
likely to suffer from depression than those eating good diets (OR=2.17, 95%CI:
1.47, 3.22). CONCLUSION: Physical activity is strongly and inversely associated
with depression and MetS. Diet is significantly associated with depression rather
than MetS in this study.
PMID- 28412645
TI - A hidden structural vulnerability in the thrombospondin-2 deficient aorta
increases the propensity to intramural delamination.
AB - Mice lacking thrombospondin-2 (TSP2) represent an animal model of impaired
collagen fibrillogenesis. Collagen constitutes ~1/3 of the wall of the normal
murine descending thoracic aorta (DTA) and is thought to confer mechanical
strength at high pressures. Microstructural analysis of the DTA from TSP2-null
mice revealed irregular and disorganized collagen fibrils in the adventitia and
at the interface between the media and adventitia. Yet, biaxial mechanical tests
performed under physiologic loading conditions showed that most mechanical
metrics, including stress and stiffness, were not different between mutant and
control DTAs at 20- and 40-weeks of age, thus suggesting that the absence of TSP2
is well compensated under normal conditions. A detailed bilayered analysis of the
wall mechanics predicted, however, that the adventitia of TSP2-null DTAs fails to
engage at high pressures, which could render the media vulnerable to mechanical
damage. Failure tests confirmed that the pressure at which the DTA ruptures is
significantly lower in 20-week-old TSP2-null mice compared to age-matched
controls (640+/-37 vs. 1120+/-45mmHg). Moreover, half of the 20-week-old and all
40-week-old mutant DTAs failed by delamination, not rupture. This delamination
occurred at the interface between the media and the adventitia, with separation
planes often observed at ~45 degrees with respect to the circumferential/axial
directions. Combined with the observed microstructural anomalies, our theoretical
experimental biomechanical results suggest that TSP2-null DTAs are more
susceptible to material failure when exposed to high pressures and this
vulnerability may result from a reduced resistance to shear loading at the
medial/adventitial border.
PMID- 28412646
TI - A longitudinal study of the mechanical properties of injured brain tissue in a
mouse model.
AB - Mechanical properties of brain tissue are crucial to understand the mechanism of
traumatic brain injury (TBI). Over the past several decades, most of the studies
focused on healthy brain tissues, while few of them are about the injured
tissues. Therefore, limited knowledge is known about the mechanical properties of
the injured brain tissues. In this study, we used an in vivo mouse model with a
weight drop device to study injured brain tissues. Around the injury site,
mechanical properties of the injured, neighboring, and the corresponding
contralateral regions of interest (ROIs) were measured over five temporal points
by indentation. Longitudinal and regional comparisons of the mechanical
properties revealed that the ROI of the injured tissue had a higher elastic
modulus than the contralateral counterpart one-hour post-injury. However, the
elastic modulus decreased one-day post-injury and recovered to be close to the
contralateral ROI in 7 days. The elastic modulus curves of the injured and the
contralateral counterpart ROIs crossed at time points of 12h and 1 day post
injury, where two significant increases of glial fibrillary acidic protein (GFAP)
positive cells were observed. Biological staining results indicated that both the
astrocytic responses and the morphological structure could affect the mechanical
properties of the injured tissue. The observed longitudinal changes of the
mechanical properties at the tissue level and the morphological and biological
changes at the cellular level provide insights into understanding the mechanism
of TBI. Results are also meaningful for applying emerging in vivo diagnostic
tools such as magnetic resonance elastography (MRE) in TBI detection.
PMID- 28412647
TI - Ecofriendly lignocellulose pretreatment to enhance the carboxylate production of
a rumen-derived microbial consortium.
AB - Innovative dry chemo- and chemo-mechanical pretreatments form an interesting
approach for modifying the native physico-chemical composition of lignocellulose
facilitating its microbial conversion to carboxylates. Here, the impact of four
dry-pretreatment conditions on the microbial transformation of wheat straw was
assessed: milling to 2mm and 100um, and NaOH chemical impregnation at high
substrate concentrations combined with milling at 2mm and 100um. Pretreatment
effect was assessed in the light of substrate structure and composition, its
impact on the acidogenic potential and the major enzyme activities of a rumen
derived microbial consortium RWS. Chemo-mechanical pretreatment strongly modified
the substrate macroporosity. The highest carboxylate production rate was reached
after dry chemo-mechanical treatment with NaOH at 100um. A positive impact of the
dry chemo-mechanical treatment on xylanase activity was observed also. These
results underline that increasing substrate macroporosity by dry chemo-mechanical
pretreatment had a positive impact on the microbial acidogenic potential.
PMID- 28412648
TI - Content decline of SERCA inhibitors saikosaponin a and d attenuates
cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri.
AB - Improper usage of unprocessed Radix bupleuri root (chaihu) may cause
cardiotoxicity and liver injury. Baking herb with vinegar is believed to
attenuate the adverse responses. However, the chemical and molecular basis
involved remained unclear. To this end, we investigated the in vitro toxicity of
saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results
showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic
reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger
toxic responses on cardiomyocytes and hepatocytes than the other three
saikosaponins in equivalent concentrations. Further, SSa and SSd induced LC3
puncta formation in U2OS-mCherry-EGFP-LC3 cells. Blockage of autophagy by 3
methyladenine did not abrogate the cytotoxicities induced by SSa and SSd. In
parallel, none of SSc, SSb1, or SSb2 caused cell injury. Our study reveals how
changes in chemical ingredients are connected to the toxicity of Chaihu during
vinegar baking process and also provides a guidance for structure optimization to
reduce drug induced toxicity.
PMID- 28412649
TI - Proinflammatory effects of diesel exhaust particles from moderate blend
concentrations of 1st and 2nd generation biodiesel in BEAS-2B bronchial
epithelial cells-The FuelHealth project.
AB - Biodiesel fuel fuels are introduced at an increasing extent as a more carbon
neutral alternative to reduce CO2-emissions, compared to conventional diesel
fuel. In the present study we have investigated the impact of increasing the use
of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend
(B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd
generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic
Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro
system. Human bronchial epithelial BEAS-2B cells were exposed for 4 and 20h to
DEP from B7, B20 and SHB at different concentrations, and examined for effects on
gene expression of interleukin 6 (IL-6), CXCL8 (IL-8), CYP1A1 and heme oxygenase
1 (HO-1). The results show that both B20 and SHB were more potent inducers of IL
6 expression compared to B7. Only B20 induced statistically significant increases
in CXCL8 expression. By comparison the rank order of potency to induce CYP1A1 was
SHB>B7>B20. No statistically significant difference were observed form HO-1
expression, suggesting that the differences in cytokine responses were not due to
oxidative stress. The results show that even moderate increases in biodiesel
blends, from 7% to 20%, may increase the proinflammatory potential of emitted DEP
in BEAS-2B cells. This effect was observed for both addition of 1st generation
FAME and 2nd generation HVO biodiesel.
PMID- 28412650
TI - Comparative effects of cholesteryl ester transfer protein inhibition, statin or
ezetimibe on lipid factors: The ACCENTUATE trial.
AB - BACKGROUND AND AIMS: The optimal approaches to management of patients treated
with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study
aimed to compare the effects of adding the cholesteryl ester transfer protein
inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin
treated high-vascular risk patients on lipid parameters. METHODS: 366 patients
with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated
with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40
mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe
10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the
United States. Lipid parameters, safety and tolerability were measured. RESULTS:
Addition of evacetrapib significantly reduced LDL-C (-33%) compared with
ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%,
p<0.001). Evacetrapib also decreased apoB by 23% compared to 19% with ezetimibe
(p=0.06) and 7% with increased statin dose (p<0.001), and reduced Lp(a) by 29%
(p<0.001 vs. other groups). Evacetrapib increased HDL-C (+125%), apoA-I (+46%),
apoC-III (+50%) and apoE (+28%) (p<0.001 vs. other groups). Non-ABCA1-mediated
efflux increased by 53% (p<0.001 vs. other groups) with evacetrapib. ABCA1
mediated efflux also increased by 13% with evacetrapib (p<0.001 vs. ezetimibe,
p=0.002 vs. increasing statin dose, and p=0.004 vs. statin alone). Addition of
evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe
(p=0.02). CONCLUSIONS: While evacetrapib improved traditional atherogenic and
putative protective lipid measures compared with ezetimibe and increasing statin
dose in patients with ASCVD and/or diabetes, it also adversely affected novel
atherogenic risk factors. These findings may contribute to the lack of clinical
benefit observed in the ACCELERATE trial.
PMID- 28412651
TI - Time-dependent effect of rutin on skin fibroblasts membrane disruption following
UV radiation.
AB - Chronic exposure of the skin to solar UV radiation induces a number of biological
alterations, including a redox imbalance; therefore, there is an urgent need for
skin cells protective compounds. The aim of this study was to determine the
effects of natural, previously extensively examined, polyphenol with antioxidant
properties - rutin, on UV-induced skin fibroblasts membrane disruption.
Accordingly, fibroblasts exposed to UVA and UVB irradiation were incubated with
rutin (12h before and/or up to 24h after irradiation), and the structural and
metabolic changes were examined. Rutin penetration through the fibroblast
phospholipid bilayer was aided by UVA-induced bilitranslocase activity 2-4h after
irradiation, while UVB irradiation led to enhanced phospholipid peroxidation and
higher membrane permeability to facilitate the interaction of rutin with
phospholipids. Lipidomic analysis revealed that 4h of rutin treatment also
partially prevented UVA/B-induced increase in phosphatidylethanolamine and
phosphatidylcholine level, as well as their membrane localization, which resulted
in an enhanced zeta potential in the cells and liposomes. Moreover, rutin 2h
following irradiation, in a various degree, prevented the increased in
phospholipase A2 activity and ROS generation, and partially protected against the
reduction of arachidonic and linoleic acids level and the lipid peroxidation
product 4-hydroxynonenal level increase. Rutin effectively prevented against
decrease in glutathione peroxidase, glutathione and vitamins E and C
activities/levels, particularly 2h following UVA irradiation. In conclusion,
highest skin fibroblasts membrane level of rutin occurred in 2-4h following UVA/B
radiation results in its strongest effect on biomembrane structure and functions
and cellular antioxidant system irrespective of the radiation type.
PMID- 28412652
TI - During yeast chronological aging resveratrol supplementation results in a short
lived phenotype Sir2-dependent.
AB - Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with
interesting biological properties/functions amongst which are its activity as an
antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins
comprise a family of NAD+-dependent protein deacetylases that are involved in
many physiological and pathological processes including aging and age-related
diseases. These enzymes are conserved across species and SIRT1 is the closest
mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging
researches, it is well known that Sir2 is a positive regulator of replicative
lifespan and, in this context, the RSV effects have been already examined. Here,
we analyzed RSV effects during chronological aging, in which Sir2 acts as a
negative regulator of chronological lifespan (CLS). Chronological aging refers to
quiescent cells in stationary phase; these cells display a survival-based
metabolism characterized by an increase in oxidative stress. We found that RSV
supplementation at the onset of chronological aging, namely at the diauxic shift,
increases oxidative stress and significantly reduces CLS. CLS reduction is
dependent on Sir2 presence both in expired medium and in extreme Calorie
Restriction. In addition, all data point to an enhancement of Sir2 activity, in
particular Sir2-mediated deacetylation of the key gluconeogenic enzyme
phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount
of the acetylated active form of Pck1, whose enzymatic activity is essential for
gluconeogenesis and CLS extension.
PMID- 28412653
TI - The relationship between dioxins exposure and risk of prostate cancer with
steroid hormone and age in Vietnamese men.
AB - Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly
injurious to health, not all causal relationships have been clarified. We
therefore explored associations among dioxins, steroid hormones, age and prostate
cancer risk in men. We compared serum levels of dioxin, steroid hormones and
prostate specific antigen (PSA) in men aged 56-81years from herbicide-exposed
hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of
dioxin congeners in the hotspot group were 1.5-11.3 times higher than the non
sprayed group depending on specific compound. Levels of testosterone, estradiol
and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity in the hotspot group
were also significantly higher than in non-sprayed group. Estradiol levels were
significantly related to levels of several specific dioxin derivatives in both
group. Significant positive correlations were also found between DHT and 1234678
HpCDD or 1234678-HpCDF; and between 3beta-HSD activity and 123678-HxCDD, 123478
HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and
tobacco use, multiple linear regressions showed levels of dihydrotestosterone
(DHT), estradiol, testosterone and 3beta-HSD activity were not associated with
dioxins in the two groups; however, levels of DHT, testosterone and 3beta-HSD
activity increased significantly with age in the hotspot group. The hotspot and
non-sprayed groups did not significantly differ in PSA levels. But six of the
hotspot subjects had PSA levels >3ng/mL, 3 of whom were suspected to have
prostate cancer (PC) after digital rectal examination. Our findings suggest that
dioxin exposure can lead to increased levels of several sex steroid hormones with
age. The correlation of dioxin with steroid hormone levels and prostate cancer
risk should be studied further.
PMID- 28412654
TI - Nigella sativa, a traditional Tunisian herbal medicine, attenuates bleomycin
induced pulmonary fibrosis in a rat model.
AB - The present study investigated the effects of Nigella sativa oil (NSO) on
bleomycin (BLM)-induced lung fibrosis in rats. The rat model of pulmonary
fibrosis (PF) was established by intratracheal instillation of BLM, and the
effect of 1ml/kg oral NSO treatment once daily observed. The effect of NSO was
studied over a period of 50daysusing 1H RMN analysis on the urine and broncho
alveolar lavage fluid (Balf) of the rats. Histopathological (inflammation and
fibrosis) and immunohistochemical (TGF-beta1 density) changes were evaluated.
Results found that the BLM group showed a significant increase in inflammatory
index (II), fibrosis score (FS) and TGF-beta1 distribution in the lung
inflammatory infiltrate, accompanied by a decreased urinary secretion of Krebs
cycle intermediates, including acetate, pyruvate, carnitine, trimethylamine-N
oxide and succinate. However, at the same time point, NSO treated rats had a
reduced II and FS, and had an increased urinary secretion of histidine, fumarate,
allantoin and malate. In conclusion, NSO treatment attenuated the effects of BLM
induced PF, by supporting lung, liver and kidney activity in resisting PF. These
findings provide an insight into the preventive and therapeutic potential of NSO
in the treatment of PF.
PMID- 28412655
TI - Parkinson's disease and pesticides: A meta-analysis of disease connection and
genetic alterations.
AB - Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that
occurs due to interactions between genetic and environmental factors.
Observational studies have shown a link between exposure to pesticides and the
risk of PD. We performed this study to systemically review published case-control
studies and estimate quantitatively the association between pesticide exposure
and PD. We searched Medline (through PubMed) for eligible case-control studies.
The association between pesticide exposure and PD risk or occurrence of certain
genetic alterations, related to the pathogenesis of PD was presented as odds
ratios (OR) and pooled under the random effects model, using the statistical add
in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is
linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant
heterogeneity among included studies. Exposure to pesticides increased the risk
of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97,
95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI
[1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no
statistically significant association between exposure to pesticides and
alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI
[0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91,
2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta
analysis provides evidence that pesticide exposure is significantly associated
with the risk of PD and alterations in genes involved in PD pathogenesis.
However, the underlying mechanism of this association and the effect of the
duration of exposure or the type of pesticides should be addressed by future
research.
PMID- 28412656
TI - Design optimization of embedded ultrasonic transducers for concrete structures
assessment.
AB - In the last decades, the field of structural health monitoring and damage
detection has been intensively explored. Active vibration techniques allow to
excite structures at high frequency vibrations which are sensitive to small
damage. Piezoelectric PZT transducers are perfect candidates for such testing due
to their small size, low cost and large bandwidth. Current ultrasonic systems are
based on external piezoelectric transducers which need to be placed on two faces
of the concrete specimen. The limited accessibility of in-service structures
makes such an arrangement often impractical. An alternative is to embed
permanently low-cost transducers inside the structure. Such types of transducers
have been applied successfully for the in-situ estimation of the P-wave velocity
in fresh concrete, and for crack monitoring. Up to now, the design of such
transducers was essentially based on trial and error, or in a few cases, on the
limitation of the acoustic impedance mismatch between the PZT and concrete. In
the present study, we explore the working principles of embedded piezoelectric
transducers which are found to be significantly different from external
transducers. One of the major challenges concerning embedded transducers is to
produce very low cost transducers. We show that a practical way to achieve this
imperative is to consider the radial mode of actuation of bulk PZT elements. This
is done by developing a simple finite element model of a piezoelectric transducer
embedded in an infinite medium. The model is coupled with a multi-objective
genetic algorithm which is used to design specific ultrasonic embedded
transducers both for hard and fresh concrete monitoring. The results show the
efficiency of the approach and a few designs are proposed which are optimal for
hard concrete, fresh concrete, or both, in a given frequency band of interest.
PMID- 28412657
TI - Potential-resolved "in-electrode" type electrochemiluminescence immunoassay based
on functionalized g-C3N4 nanosheet and Ru-NH2 for simultaneous determination of
dual targets.
AB - Here, a novel potential-resolved "in-electrode" type electrochemiluminescence
(ECL) immunosensor was fabricated based on two different types of luminant Ru-NH2
and AuNPs/g-C3N4 to realize simultaneous detection of dual targets. In this
strategy, anti-CA1251 and anti-SCCA1 were immobilized on bare gold electrode as
capture probes, which could catch the two corresponding target CA125 and SCCA,
and the immobilization of the signal tags was allowed via the interaction between
antigen and antibody. In this process, (Ru&anti-CA1252)@GO and anti-SCCA2-AuNPs/g
C3N4 could exhibit two strong and stable ECL emissions at 1.25V and -1.3V
respectively, which could be used as effective signal tags. Taking advantage of
"in-electrode" type ECL immunosensor, all the electrochemiluminophores near the
outer Helmholtz plane are "effective" in participating in the electrochemical
reactions and emitting ECL signals. Therefore, the dual targets CA125 and SCCA
could be detected within the linear ranges of 0.001-100U/mL and 0.001-100ng/mL,
with detection limits of 0.4mU/mL and 0.33pg/mL, respectively. All these results
demonstrated that the present potential-resolved "in-electrode" type
electrochemiluminescence approach provided a promising analytical method for dual
targets analysis with the advantages of simple analytical procedure, small sample
volume and lower cost, which made the proposed method potential for clinical
detection.
PMID- 28412658
TI - CdS:Mn quantum dot-functionalized g-C3N4 nanohybrids as signal-generation tags
for photoelectrochemical immunoassay of prostate specific antigen coupling
DNAzyme concatamer with enzymatic biocatalytic precipitation.
AB - A new photoelectrochemical (PEC) immunosensor based on Mn-doped CdS quantum dots
(CdS:Mn QDs) on g-C3N4 nanosheets was developed for the sensitive detection of
prostate specific antibody (PSA) in biological fluids. The signal derived from
the as-synthesized Cd:Mn QDs-functionalized g-C3N4 nanohybrids via a hydrothermal
method and was amplified through DNAzyme concatamers on gold nanoparticles
accompanying enzymatic biocatalytic precipitation. Experimental results by UV-vis
absorption spectra and photoluminescence revealed that CdS:Mn QDs/g-C3N4
nanohybrids exhibited higher photocurrent than those of CdS:Mn QDs and g-C3N4
alone. Upon addition of target PSA, a sandwich-type immunoreaction was carried
out between capture antibodies and the labeled detection antibodies. Accompanying
introduction of gold nanoparticles, the labeled initiator strands on the AuNPs
triggered hybridization chain reaction and the formation of DNAzyme concatamers
in the presence of hemin. The formed DNAzyme catalyzed 4-chloro-1-naphthol (4-CN)
to produce an insoluble/insulating precipitate on the Mn:CdS QDs/g-C3N4, and
blocked the light harvesting of Mn:CdS QDs/g-C3N4, thus resulting in the
decreasing photocurrent. Under optimal conditions, the immunosensor exhibited
good photocurrent responses for determination of target PSA, and allowed
detection of PSA at a concentration as low as 3.8pgmL-1. The specificity,
reproducibility and precision of this system were acceptable. Significantly, this
methodology was further evaluated for analyzing human serum samples, giving well
matched results with referenced PSA enzyme-linked immunosorbent assay (ELISA)
method.
PMID- 28412659
TI - Development of near-infrared ratiometric fluorescent probe based on cationic
conjugated polymer and CdTe/CdS QDs for label-free determination of glucose in
human body fluids.
AB - Quantum dots (QDs) have attracted extensive attention in biomedical applications,
because of their broad excitation spectra, narrow and symmetric emission peaks
etc. Furthermore, near-infrared (NIR) QDs have further advantages including low
autofluorescence, good tissue penetration and low phototoxicity. In this work,
the electrostatic interaction and fluorescence resonance energy transfer (FRET)
between NIR CdTe/CdS QDs and cationic conjugated polymer (CCP) was studied for
the first time. Based on the newly discovered phenomena and the result that
hydrogen peroxide (H2O2) can efficiently quench the fluorescence of NIR CdTe/CdS
QDs, a novel NIR ratiometric fluorescent probe for determination of H2O2 and
glucose was developed. Under the optimized conditions, the detection limit of
H2O2 and glucose assay were 0.1mM and 0.05mM (S/N=3), with a linear range of 0.2
4mM and 0.1-5mM, respectively. Because of the NIR spectrum, this ratiometric
probe can be also applied for the determination of glucose in whole blood samples
directly, providing a valuable platform for glucose sensing in clinic diagnostic
and drug screening.
PMID- 28412660
TI - Gold nanoparticle-based low limit of detection Love wave biosensor for
carcinoembryonic antigens.
AB - In this work, a Love wave biosensing platform is described for detecting cancer
related biomarker carcinoembryonic antigen (CEA). An ST 90 degrees -X quartz Love
wave device with a layer of SiO2 waveguide was combined with gold nanoparticles
(Au NPs) to amplify the mass loading effect of the acoustic wave sensor to
achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au
NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich
immunoassay. The unamplified detection limit of the Love wave biosensor is
9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings
the SAW platform into the range useful for clinical diagnosis. Measurement
electronics and microfluidics are easily constructed for acoustic wave
biosensors, such as the Love wave device described here, allowing for robust
platforms for point of care applications for cancer biomarkers in general.
PMID- 28412661
TI - Reliable clinical serum analysis with reusable electrochemical sensor: Toward
point-of-care measurement of the antipsychotic medication clozapine.
AB - Clozapine is one of the most promising medications for managing schizophrenia but
it is under-utilized because of the challenges of maintaining serum levels in a
safe therapeutic range (1-3MUM). Timely measurement of serum clozapine levels has
been identified as a barrier to the broader use of clozapine, which is however
challenging due to the complexity of serum samples. We demonstrate a robust and
reusable electrochemical sensor with graphene-chitosan composite for rapidly
measuring serum levels of clozapine. Our electrochemical measurements in clinical
serum from clozapine-treated and clozapine-untreated schizophrenia groups are
well correlated to centralized laboratory analysis for the readily detected uric
acid and for the clozapine which is present at 100-fold lower concentration. The
benefits of our electrochemical measurement approach for serum clozapine
monitoring are: (i) rapid measurement (~20min) without serum pretreatment; (ii)
appropriate selectivity and sensitivity (limit of detection 0.7MUM); (iii)
reusability of an electrode over several weeks; and (iv) rapid reliability
testing to detect common error-causing problems. This simple and rapid
electrochemical approach for serum clozapine measurements should provide
clinicians with the timely point-of-care information required to adjust dosages
and personalize the management of schizophrenia.
PMID- 28412662
TI - A wireless point-of-care testing system for the detection of neuron-specific
enolase with microfluidic paper-based analytical devices.
AB - Neuron-specific enolase (NSE) had clinical significance on diagnosis, staging,
monitoring effect and judging prognosis of small cell lung cancer. Thus, there
had a growing demand for the on-site testing of NSE. Here, a wireless point-of
care testing (POCT) system with electrochemical measurement for NSE detection was
developed and verified. The wireless POCT system consisted of microfluidic paper
based analytical devices (MUPADs), electrochemical detector and Android's
smartphone. Differential pulse voltammetry (DPV) measurement was adopted by means
of electrochemical detector which including a potentiostat and current-to-voltage
converter. MUPADs were modified with nanocomposites synthesized by Amino
functional graphene, thionine and gold nanoparticles (NH2-G/Thi/AuNPs) as
immunosensors for NSE detection. Combined with MUPADs, the performance of the
wireless POCT system was evaluated. The peak currents showed good linear
relationship of the logarithm of NSE concentration ranging from 1 to 500ngmL-1
with the limit of detection (LOD) of 10pgmL-1. The detection results were
automatically stored in EEPROM memory and could be displayed on Android's
smartphone through Bluetooth in real time. The detection results were comparable
to those measured by a commercial electrochemical workstation. The wireless POCT
system had the potential for on-site testing of other tumor markers.
PMID- 28412663
TI - A facile, rapid and sensitive detection of MRSA using a CRISPR-mediated DNA FISH
method, antibody-like dCas9/sgRNA complex.
AB - Rapid and reliable diagnosis of methicillin-resistant Staphylococcus aureus
(MRSA) is crucial for guiding effective patient treatment and preventing the
spread of MRSA infections. Nonetheless, further simplification of MRSA detection
procedures to shorten detection time and reduce labor relative to that of
conventional methods remains a challenge. Here, we have demonstrated a Clustered
regularly interspaced palindromic repeats (CRISPR)-mediated DNA-FISH method for
the simple, rapid and highly sensitive detection of MRSA; this method uses CRISPR
associated protein 9/single-guide RNA (dCas9/sgRNA) complex as a targeting
material and SYBR Green I (SG I) as a fluorescent probe. A dCas9/sgRNA-SG I based
detection approach has advantages over monoclonal antibody in conventional
immunoassay systems due to its ability to interact with the target gene in a
sequence-specific manner. The detection limit of MRSA was as low as 10 cfu/ml and
was found to be sufficient to effectively detect MRSA. Unlike conventional gene
diagnosis methods in which PCR must be accompanied or genes are isolated and
analyzed, the target gene can be detected within 30min with high sensitivity
without performing a gene separation step by using cell lysates. We showed that
the fluorescence signal of the MRSA cell lysate was more than 10-fold higher than
that of methicillin-susceptible S. aureus (MSSA). Importantly, the present
approach can be applied to any target other than MRSA by simply changing the
single-guide RNA (sgRNA) sequence. Because dCas9/sgRNA-SG I based detection
approach has proved to be easy, fast, sensitive, and cost-efficient, it can be
applied directly at the point of care to detect various pathogens as well as MRSA
in this study.
PMID- 28412664
TI - New model for prediction binary mixture of antihistamine decongestant using
artificial neural networks and least squares support vector machine by
spectrophotometry method.
AB - In the present study, artificial neural networks (ANNs) and least squares support
vector machines (LS-SVM) as intelligent methods based on absorption spectra in
the range of 230-300nm have been used for determination of antihistamine
decongestant contents. In the first step, one type of network (feed-forward back
propagation) from the artificial neural network with two different training
algorithms, Levenberg-Marquardt (LM) and gradient descent with momentum and
adaptive learning rate back-propagation (GDX) algorithm, were employed and their
performance was evaluated. The performance of the LM algorithm was better than
the GDX algorithm. In the second one, the radial basis network was utilized and
results compared with the previous network. In the last one, the other
intelligent method named least squares support vector machine was proposed to
construct the antihistamine decongestant prediction model and the results were
compared with two of the aforementioned networks. The values of the statistical
parameters mean square error (MSE), Regression coefficient (R2), correlation
coefficient (r) and also mean recovery (%), relative standard deviation (RSD)
used for selecting the best model between these methods. Moreover, the proposed
methods were compared to the high- performance liquid chromatography (HPLC) as a
reference method. One way analysis of variance (ANOVA) test at the 95% confidence
level applied to the comparison results of suggested and reference methods that
there were no significant differences between them.
PMID- 28412665
TI - Quantitation of levodopa and carbidopa in rat plasma by LC-MS/MS: The key role of
ion-pairing reversed-phase chromatography.
AB - A simple and selective bioanalytical method was developed for simultaneous
determination of levodopa and carbidopa in rat plasma by LC-MS/MS. Levodopa and
carbidopa are small polar molecules, posing challenges in the development of
selective and efficient chromatography conditions. Perfluoropentanoic acid
(PFPA), a volatile ion-pairing agent, was utilized to enhance chromatographic
characteristics of both compounds in the reversed-phase mechanism. The ion
pairing chromatography played an essential role in mitigating matrix effects and
achieving adequate separation between interfering background peaks and those of
the analytes of interest, especially for levodopa. A 96-well based, automated
liquid-liquid extraction, via the use Hamilton NIMBUS liquid handlers, was
developed. Butyl alcohol, when mixed with ethyl acetate, greatly increased the
recovery of both levodopa and carbidopa. The addition of PFPA further enhanced
recovery for both analytes. Sodium metabisulfite, an antioxidant, was used to
stabilize levodopa and carbidopa in rat plasma. The method was validated in the
ranges of 50-10,000ng/mL and 25-5000ng/mL for levodopa and carbidopa,
respectively, using levodopa-d3 and carbidopa-d3 as internal standards. The
validated method was successfully applied to analyze rat plasma samples from in
life studies.
PMID- 28412666
TI - Student nurses' perceptions of clinical placements in Australian Prison Health
Services: A mixed methods study.
AB - Increasing demands for clinical placements have forced tertiary institutions to
look for alternative placements for third year nursing students. While Prison
Health Services provide an opportunity for nursing students to engage in care of
offender populations with significant chronic illnesses, there has been little
evaluation of such placements. Third year undergraduate nurses (18/46)
participated in a mixed methods study to provide evidence-based research on
students' perceptions of clinical placements in Prison Health Services.
Quantitative and qualitative data were collected via an anonymous survey and
individual interview. Whilst the majority of students valued the opportunity to
increase their knowledge and clinical skills and felt supported by preceptors,
challenges included being psychologically ill-prepared for the physical and
emotional aspects of placement, and witnessing poor attitudes and behaviours of
staff, which impacted on the quality of their experience. Recommendations include
changes to orientation programs and introduction of simulation to help students
feel better prepared and supported during placements in prison settings. Refining
the selection process for placements in this setting will also help to ensure
student suitability for clinical placement in Prison Health Services.
PMID- 28412667
TI - Nurses' perceptions of the impact of Team-Based Learning participation on
learning style, team behaviours and clinical performance: An exploration of
written reflections.
AB - Team-Based Learning (TBL) is a teaching strategy designed to promote problem
solving, critical thinking and effective teamwork and communication skills;
attributes essential for safe healthcare. The aim was to explore postgraduate
student perceptions of the role of TBL in shaping learning style, team skills,
and professional and clinical behaviours. An exploratory descriptive approach was
selected. Critical care students were invited to provide consent for the use for
research purposes of written reflections submitted for course work requirements.
Reflections of whether and how TBL influenced their learning style, teamwork
skills and professional behaviours during classroom learning and clinical
practice were analysed for content and themes. Of 174 students, 159 participated.
Analysis revealed three themes: Deep Learning, the adaptations students made to
their learning that resulted in mastery of specialist knowledge; Confidence, in
knowledge, problem solving and rationales for practice decisions; and
Professional and Clinical Behaviours, including positive changes in their
interactions with colleagues and patients described as patient advocacy,
multidisciplinary communication skills and peer mentorship. TBL facilitated a
virtuous cycle of feedback encouraging deep learning that increased confidence.
Increased confidence improved deep learning that, in turn, led to the development
of professional and clinical behaviours characteristic of high quality practice.
PMID- 28412668
TI - Electroporation of tissue and cells: A three-equation model of drug delivery.
AB - The exposure of the cell membrane to electric pulses of sufficient intensity is
known to result in an increased permeability due to the formation of microscopic
pores. This is electroporation, and it has been implemented to increase the
efficacy of targeted drug delivery. In this study we introduce a novel three
equation model of transport that is able to distinguish the drug uptake in
reversibly electroporated cells from that in irreversibly electroporated cells.
In order to relate the permeability increases and the cell survival to the local
electric field, sigmoidal functions are fit to published experimental data. The
resealing of reversibly electroporated cells is also considered. A numerical
study is presented that considers two different electrode configurations with
different initial drug distributions. This model is able to capture the existence
of an optimal applied voltage, above which any increases in voltage act to
decrease the total drug delivery to the surviving cells, illustrating the
competing influences of increased cell permeability and decreased cell survival.
PMID- 28412669
TI - Measurement of frontal lobe volume and thalamic volume in fetuses with congenital
heart disease at different gestational weeks using three dimensional ultra
sonography and its clinical value.
AB - Our study aimed to investigate the measurement of frontal lobe volume and
thalamic volume in fetuses with congenital heart disease (CHD) at different
gestational weeks using three dimensional (3-D) ultrasonography and its clinical
value. Then, 238 pregnant women who received obstetric ultrasonography in
ultrasound department of Internal Medicine of our hospital were enrolled between
March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD
by prenatal fetal echocardiography, and the other 153 fetuses were normal.
Frontal lobe volume, thalamic volume and cerebral blood flow was determined by
color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of
MCA-PI and CPR in CHD fetus group performed significantly lower than that in
normal fetus group (P<0.05), but the level of UA-PI performed significantly
higher than that in normal fetus group (P<0.05). When gestational age <30 weeks,
there was no significant difference in thalamic volume and frontal lobe volume
between the two groups (P<0.05); when gestational age <30 weeks, the level of CHD
fetus group performed significantly lower thalamic volume and frontal lobe volume
than that in normal fetus group (P<0.05). When gestational age <30 weeks, there
was no significant difference in BPD, HC, and GA between the two groups (P<0.05);
when gestational age <30 weeks, the level of BPD, HC and GA in CHD fetus group
performed significantly lower than that in normal fetus group (P<0.05). If
gestational age <30 weeks, CHD performed a small impact on fetal frontal lobe
volume and thalamic volume; if gestational age <30 weeks, the level of frontal
lobe volume and thalamic volume in fetuses with CHD performed significantly lower
than that in normal fetuses.
PMID- 28412670
TI - Influences of granulocyte growth factor in uterine perfusion on pregnancy outcome
of patients with failure of embryo implantation for unknown reason.
AB - To investigate the influence of granulocyte growth factor in uterine perfusion on
the pregnancy outcome of patients with failure of embryo implantation for unknown
reason. Then, 68 patients with failure of embryo implantation for unknown reason
were enrolled in our hospital from November 2013 to February 2015, which were
divided into observation group and control group by random (34 patients in each
group). Patients in observation group received basic treatment for granulocyte
growth factor in uterine perfusion on the next day, while patients in control
group received basic treatment with placebo. Then, endometrial preparation,
adverse reaction and pregnancy outcome of patients were compared between the two
groups. Comparing the endometrial preparation and average endometrial thickness
of patients in control group (9.87+/-2.12) with those in observation group
[(9.87+/-2.12), there is no significant difference (P<0.05). After treatment,
patients in both groups performed diabetes, hypertension and other pregnancy
complications without difference of statistical significance (P<0.05). The embryo
implantation rate and clinical pregnancy rate of patients in observation group
were significantly higher than those in control group [(82.35%) and (44.12%) vs
(52.94%) and (17.65%)]. Moreover, the live birth rate of patients in observation
group performed significantly higher than that in control group [(41.18%) vs
(14.71%)] with significant difference (P<0.05). By taking treatment of
granulocyte growth factor, patients with failure of embryo implantation can
effectively improve clinical pregnancy rate and embryo implantation rate without
severe complication. Therefore, treatment of granlocyte growth factor can improve
the pregnancy outcome of patients.
PMID- 28412671
TI - Role of SDF-1 and CXCR4 in the proliferation, migration and invasion of cervical
cancer.
AB - This study was to investigate the role of stromal cell-derived factor 1 (SDF-1)
and its corresponding receptor CXCR4 in the proliferation, migration and invasion
of cervical cancer HeLa cells. CXCR4 expression in HeLa cells was measured by
flow cytometry and Western Blot. Role of SDF-1 and CXCR4 in the HeLa cells
proliferation was measured by MTT. Role of SDF-1 and CXCR4 in the migration and
invasion of HeLa cell was measured by Boyden chamber. High expression of CXCR4
was observed on the surface of HeLa cells. Proliferation ability of HeLa cells
was significantly increased after SDF-1 stimulation, which showed dose-dependent
manner. After knock-down of CXCR4 expression by RNAi, SDF-1-stimulated HeLa cells
proliferation was significantly blocked (P<0.05). SDF-1 can induce migration and
invasion of Hela cells, SDF-1-stimulated HeLa cells migration and invasion was
significantly blocked (P<0.05) after knock-down of CXCR4 expression by RNAi. High
expression of surface CXCR4 plays an important role in the proliferation,
migration and invasion of HeLa cells.
PMID- 28412672
TI - Relationship between Alzheimer's disease and mitochondria coenzyme II Gene.
AB - We aimed to investigate the relevance between Alzheimer's disease (AD) and gene
mutations of mitochondrial cytochrome oxidase subunit III (COX3) and coenzyme II
(ND2), and to provide genetic markers for the diagnosis of Alzheimer's disease
(AD) and further provide some feasible basis for preventive treatment. Polymerase
chain reaction-restriction fragment length polymorphism technique was used, and
genotypes and gene frequencies were detected in 60 patients with Alzheimer's
disease (AD), who meet the ICD-10 diagnostic criteria (AD group), 10 AD families
and 60 normal old people (control group). (1) Gene variation on nt5460 gene locus
of mitochondria ND2 of the patient group is G->A, and the variation rate is
13.3%, P=0.006 < 0.05. Gene variation G->A of the patient group perfomred
statistical significance. (2) In the families, it is also found that in the gene
variation of G->A, the variation rate is 33.3%, P > 0.05. There is obvious gene
variation in the families, but this variation does not perform statistical
significance. (3) There is no gene variation on nt9861 gene locus of mitochondria
COX3 of the patient group. Gene variation of T->C is not found both in the
patient group and the control group. There is possible a gene mutation of G->A on
nt5460 gene locus of mitochondria ND2 of the AD patients. Although gene mutation
of G->A is found in the families, it performed no statistical significance. At
the same time, it is found that there is no relation between AD patients and Gene
variation of T->C on nt9861 gene locus of mitochondria COX3.
PMID- 28412673
TI - Effect of controlled hypotension on myocardial ischemia marker in eye-nose
related surgery.
AB - We aimed to investigate the effect of different controlled hypotension levels on
myocardial enzymes and myocardial ischemia protein in elderly hypertension
patients, and then provide clinical evidence of suitable controlled hypotension
level for them. Then, 45 elderly hypertension patients received elective eye-nose
related surgery with nasal endoscope, who were randomly and evenly divided into
three groups, including A, B and C groups, with mean arterial pressure (MAP)
decreased by 20%, 30% and 40% respectively. The change of myocardial enzymes,
myocardial ischemia modified albumin, score of surgical field quality and 12-lead
electrocardiogram at different perioperative points were recorded. Then operative
time, urine output and postoperative adverse complications of the patients were
recorded too. Myocardial enzymes of group C were higher than that of both group A
and B at T4, T5 points (p<0.05); Myocardial ischemia modified albumin of group C
were higher than that of group A and B at T2, T3, T4 and T5 points (p<0.05); The
score of surgical field quality of group A were higher than that of group B and C
(p<0.05); Operation time of group C is less than that of group A and B (p< 0.05);
The change of ST segment in group C is more obvious than that in group A and B
(p<0.05); The incidence of adverse complications of group C is higher than that
of group A and B (p<0.05). Controlled hypotension with MAP reduced by 30% brings
minimum myocardial damage and fewer complications, while meeting the demand of
surgical field. Thus it is an ideal controlled hypotension level and can be used
for elderly hypertension patients safely.
PMID- 28412674
TI - Analysis of relevant risk factors for intrauterine death of fetuses in the third
trimester of pregnancy.
AB - Our study aimed to explore the relevant risk factors for intrauterine death of
fetuses in the third trimester of pregnancy via a retrospective analysis. Then,
98 pregnant women with intrauterine death of fetuses in the third trimester of
pregnancy were enrolled, who had undergone the induced labor of dead fetuses in
our hospital from January, 2013 to January, 2015. By taking their disease
conditions into considerations, methods of induced labor as softening of cervix
with dinoprostone suppositories and amniotic infusion of ethacridine or oxytocin
were performed, and the timely cesarean section for termination of pregnancy was
performed. After the treatment, a detailed medical history was recorded,
including their family history, past history and conditions of this pregnancy.
Besides, autopsy of dead fetuses and pathological examinations were performed as
well as chromosome examinations of the placenta, the umbilical cord and the fetal
membrane in an attempt to identify the relevant factors for causes of death, so
as to do a good job in the post-natal consultation. The induced labor procedures
were successfully performed on all pregnant women, and the investigation of
causes of intrauterine death showed that placental factors were responsible for
the largest proportion of all causes of intrauterine death in single (28
patients), which was 31.82%, including 13 patients with placenta praevia and 13
with placental abruption. The secondary factors were umbilical cord factors,
accounting for 30.68%. Among the factors of pregnant women, gestational
hypertension occurred in 7 patients, accounting for 58.33% of factors of pregnant
women. While among the causes of intrauterine death in twins, umbilical cord
factors were found to be the main causes of death, accounting for 30.00%,
followed by placental factors and factors of pregnant women, which accounted for
20.00%, respectively. Placenta factors, umbilical cord factors and factors of
pregnant women were the main causes of intrauterine death of fetuses in the third
trimester of pregnancy. Therefore, pregnancy tests on time for routine screening
is recommended for pregnant women so as to identify the potential risk factors in
time and actively carry out symptomatic treatment, thereby reducing the chances
of intrauterine death of fetuses and improving the qualities of pregnancy. It is
worth clinical attention.
PMID- 28412675
TI - Paired observation on light-cured composite resin and nano-composite resin in
dental caries repair.
AB - To compare the value of light-cured composite resin with that of nano-composite
resin in dental caries repair. 88 patients taking dental caries repair in our
hospital from May 2014 to April 2015 were selected, and divided into observation
group and control group by coin method with 44 patients in each group. Nano
composite resin was used in observation group, while light-cured composite resin
in control group. Then, the occurrence rates of odontohyperesthesia, aesthetic
satisfaction with dental caries repair and complications were compared between
two groups by visual analogue scale (VAS). The occurrence rate of
odontohyperesthesia in observation group is significantly lower than that in
control group (9.09% (4/44) vs 31.82% (14/44), 6.82% (3/44) vs 22.73% (10/44),
2.27% (1/44) vs 13.64% (6/44)) with difference of statistical significance
(P<0.05) 1 week, 4 weeks, and 8 weeks after repair. VAS score of patients in
observation is significantly lower than that in control group ((2.78+/-0.56)
scores vs (5.22+/-0.76) scores, (2.02+/-0.35) scores vs (4.32+/-0.57) scores,
(1.12+/-0.14) scores vs (2.41+/-0.43) scores) 1 week, 4 weeks, and 8 weeks after
repair. Moreover, the difference in comparison of interactive effects between two
groups, between different time points, and between groups at different time
points has statistical significance (P<0.05). Nano-composite resin can lower the
occurrence rate of odontohyperesthesia in dental caries repair, reduce the pain
of patients, and improve the satisfaction of patients with tooth appearance.
PMID- 28412676
TI - Investigation of sub-health status of neonates in Heping street region (Beijing)
and analysis on related risk factors.
AB - To investigate sub-health status of neonates in Heping Street Region and related
risk factors. Then, 7436 maternal women admitted to hospital in Heping Street
Region, Beijing were enrolled from October 2013 to September 2015, including 293
women, who gave birth to sub-health neonates. Questionnaire survey was conducted
to collect maternal age, education degree, experiences and income, occupation,
life habit, condition in pregnancy, condition in perinatal period, adverse
reaction in pregnancy, etc. Finally, 281 effective questionnaires were regained
with effective regain rate of 95.90%. Compared with the occurrence rate of sub
health neonates between local population and floating population, correlation
analysis and multi-factor Logistic regression analysis were conducted on the
influence factors of sub-health neonates. The occurrence rate of sub-health
neonates among floating population is higher than that among local population
(1.10% (59/2641) V.S. 4.88% (234/4795)) with significant difference (P<0.05).
Correlation analysis showed that the differences in mother's age, family income,
education degree, harmful factors in contact environment, prenatal care, history
of adverse pregnancy, unhealthy metal factor, gestational diabetes, diseases
history in pregnancy, drug history in pregnancy, sexually transmitted disease,
pregnancy hypertension, premature rupture of fetal membranes, and circular of
umbilical cord performed statistical significance (P<0.05). Moreover, mother's
age, premature rupture of fetal membranes, disease history in pregnancy, drug
history in pregnancy and pregnancy hypertension are the influence factors for the
risk of sub-health neonates, while high family income and healthcare in pregnancy
are protective factors from the risk of sub-health neonates. All of these
differences showed statistical significance (P<0.05). The occurrence of sub
health neonates among floating population is higher than that among local
population. Mother's age, premature rupture of fetal membranes, disease history
in pregnancy, drug history in pregnancy, and pregnancy hypertension are major
risk factors of sub-health neonates. Therefore, these results help us to take
corresponding measures to improve the quality of newly-born population.
PMID- 28412677
TI - Differential analysis of clinical efficacy on patients with serious infection in
ICU by different meropenem regimens.
AB - To investigate the difference in clinical efficacy and safety of different
meropenem regimens on patients with serious infection in ICU. Then, 228 patients
with serious infection in ICU were divided by random into control group
(intermittent administration in 1000mg/30min single dose) and research group
(continuous administration in 200mg/10min +800mg/180min), respectively. The blood
concentration of meropenem were recorded in two groups at different time points,
and difference in treatment effectiveness, iconographic effectiveness, bacterial
eradication rate, 28-day survival rate and many other clinical scoring indices
(SOFA, APACHEII, CPIS, and SIRS) were compared between two groups. There were 212
patients completing the whole research, including 104 patients in research group
and 108 patients in control group. The difference in treatment effectiveness
(77.8% vs 53.7%), iconographic effectiveness (51.0% vs 18.5%), and 28-day
survival rate (86.5% vs 64.8%) between two groups performed statistical
significance (P<0.05). However, the difference in bacterial eradication rate
(48.0% vs 46.3%) performed no statistical significance. Eight hours later, the
difference in average blood concentration between two groups (9.61+/-3.63MUg/ml
vs 1.5+/-0.51MUg/ml) showed statistical significance. Moreover, the difference in
clinical scoring indices except APACHE II score between two groups performed
statistical significance. It was helpful to maintain the blood concentration of
meropenem by extending the transfusion time. Therefore, it could increase the
clinical cure rate and 28-day survival of patients with serious infection in ICU,
improve clinical indices, and reduce the usage amount of antibiotics.
PMID- 28412678
TI - Clinical study of lung-supplementing and stasis-dissolving decoction (Bufei Huayu
Tang) combined with gefitnib for treatment of advanced non-small cell lung
cancer.
AB - To investigate the clinical efficacy and drug safety of Lung-Supplementing and
Stasis-Dissolving Decoction (Bufei Huayu Tang) combined with gefitnib for
treatment of advanced non-small cell lung cancer (NSCLC). Then, 80 patients with
advanced NSCLC hospitalized in Ruikang Hospital Affiliated to Guangxi University
of Chinese Medicine were included, and were double-blindly randomized into 4
groups: control group (gefitinib alone 250mg, once daily), low-dose group
(100mL/day), middle-dose group (150mL/day) and high-dose group (200mL/day)
treated with different doses of Bufei Huayu Tang besides gefitinib. Clinical
efficacy, life quality change before and after treatment, ECOG score, survival
time and incidence of adverse drug reaction were compared. ECOG score in middle
dose group after treatment was significantly higher than other groups (P<0.05).
Total efficiency of 4 groups was respectively 15%, 20%, 55% and 25%, and total
efficiency in middle-dose group was significantly higher than that in other
groups (P<0.05). According to TCM syndrome score, the improvement in middle-dose
group was significantly better than that in other groups (P<0.05). Incidence of
adverse drug reaction in high-dose group was significantly higher than that in
other 3 groups (P<0.05). Self-designed Bufei Huayu Tang combined with gefitinib
for NSCLC has a satisfactory clinical efficacy and high drug safety. Decoction
dose needs more attention.
PMID- 28412679
TI - Epidemic characteristics of main infectious diseases in Yantai city between 2010
and 2012 and prevention strategy research.
AB - To investigate the epidemic characteristics and prevention strategies of main
infectious diseases. From 2010 to 2012, 23 notifiable diseases were reported in
Yantai with average reported cases of 17,376. The morbidity was the highest in
2012 and the lowest in 2011. The accumulated death toll was 101 with the highest
death rate in 2011 and the lowest in 2012. Major class A and B infectious
diseases included viral hepatitis, phthisis, syphilis, clap and dysentery. The
major class C infectious disease was hand-foot-and-mouth disease every year. The
distribution of transmission routes of HIV/AIDS among patients with HIV and AIDS
in Yantai were investigated. The overall condition of phthisis in Yantai showed
stable with slight decrease. The occurrence rate of phthisis every season had
fluctuation with higher rate in middle two seasons and lower rate at the
beginning and end. The major type of viral hepatitis was still hepatitis B.
Patients with hand-foot-and-mouth disease were children under 5 years old
accounting for 90.56%, mainly reported in May, June, July and August. At present,
the condition of plague prevention for infectious diseases in Yantai is not
optimistic with both new and old infectious diseases.
PMID- 28412680
TI - Study on effect of Combivent combined with glucocorticoids in the treatment of
patients with AECOPD.
AB - We observed the effect of Combivent combined with glucocorticoids in the
treatment of patients with AECOPD to explore a better drug treatment for AECOPD.
The clinical observation of two clinical curative effective was carried out.
Firstly, 100 patients were equally divided into treatment group and control
group, who were given basic treatment. The control group was treated with
inhalation of salbutamol sulfate and the other was with inhalation of Combivent
and glucocorticoid. The clinical effect, dyspnea score, PaO2, PaCO2 and pulmonary
function index were observed and compared. The second, 100 patients with AECOPD
were divided into the conventional group, the short range group and the long
range group, all of that were treated with inhalation of Combivent. The short and
the long were treated with glucocorticoid for 7d and 15d.Pulmonary function index
was monitored at sixth and fifteenth days after treatment. The incidence of
AECOPD was compared with the incidence of complication. Firstly, after 10 days of
treatment, the treatment group's total efficiency, dyspnea score, PaO2, PaCO2,
were significantly better than the control group and the treatment in the two
groups after the above indexes were significant better than those before
treatment. The differences were statistically significant (P<0.05). The second
time, the short and the long's VC, FVC, FEV1 were higher than the conventional,
the recurrence rate was decreased, the incidence of complications in the short
was significantly lower than that in the long and the difference was
statistically significant (P<0.05). The effect of Combivent combined with
glucocorticoid was exactly and the short's complication was low, which is worth
to be popularized.
PMID- 28412681
TI - Research on in vitro release of Isoniazid (INH) super paramagnetic microspheres
in different magnetic fields.
AB - To explore in vitro release rules of isoniazid (INH) when Isoniazid Super
paramagnetic Iron Oxide Microspheres (ISPIOM) are subject to no external magnetic
field, applied mechanical magnetic field and scillating magnetic field. ISPIOM
was prepared by using the spray drying method; Isoniazid contented in the
microspheres was determined, the drug loading capacity and encapsulation
efficiency were calculated. Release of isoniazid in the microspheres was
determined respectively under the effect of no external magnetic field, applied
mechanical magnetic field and oscillating magnetic field, to explore the release
rules. In solution with pH=7.4 PBS, microspheres featured 8-hour sustained
release under the effect of magnetic field, the released rate of the microspheres
is accelerated,. In solution with pH=3 PBS, microspheres release faster and could
realize the fastest completion of release in 2 hours under the effect of
oscillating magnetic field. To join the external magnetic field in different
point time to can't affect the release, under pH=3 of medium, ISPIOM release
faster; under the effect of magnetic field, the released rate of the microspheres
is accelerated, and the longer effect of magnetic field, the faster release.
Oscillating magnetic field can make ISPIOM within a certain period of time, get
ideal release curve, so as to achieve good control release effect.
PMID- 28412682
TI - Application frequency and therapeutic effect of Astragalus in treating ischemic
cerebrovascular disease.
AB - In recent years, Traditional Chinese Medicine (TCM) therapy has achieved
substantial progress and development, playing an important role in clinical
practice. In this paper, to explore the therapeutic effect of Astragalus in
treating ischemic cerebrovascular disease, 2687 patients with ischemic
cerebrovascular disease who had been treated with Astragalus therapy from Jan
2014-Oct 2015 were selected as the research objects. Through retrospective
analysis of their medical records, we analyzed the application frequency of
Astragalus using quantitative method of information, and conducted specific
analysis on the therapeutic effect of Astragalus after fully surveyed patients'
physical conditions after treatment. Results show that in the treatment of
ischemic cerebrovascular disease by TCM, Astragalus is of high application
frequency and sound therapeutic effect, which is deserved to be applied and
promoted in clinical practices.
PMID- 28412683
TI - Safety in Treating Primary Acute Angle-closure Glaucoma under High Intraocular
Pressure by Compound Trabeculectomy.
AB - In clinical practice, Primary Acute Angle-closure Glaucoma (APACG) is a common
disease with an increasing incidence rate and blind rate, and has attracted
attention of medical researchers. When a patient suffers both primary acute
glaucoma and high tension glaucoma, drug therapy can achieve limited efficacy,
and operative treatment is necessary on this occasion. This research mainly
explored the safety in treating high tension APACG by compound trabeculectomy,
and observed the clinical treatment effect and incident rate of postoperative
complications after compound trabeculectomy. The compound trabeculectomy can
effectively control the intraocular pressure and decrease the incident rate of
postoperative complications, accelerating the rehabilitation of patients.
PMID- 28412684
TI - Clinical application analysis of continuing nursing in nursing service for
diabetic patients.
AB - : The research is to establish a Continuing Nursing Project after discharge which
conforming to the actual conditions of our country and explore whether such
Continuing Nursing Project could effectively improve therapy compliance and blood
glucose control of diabetic patients. METHODS: mainly analyzing pathological
mechanisms of diabetic patients and exploring the clinical effect and the
complication after implementing Continuing Nursing to patients. RESULTS: after
implementing Continuing Nursing, the diabetic patients could be better at
controlling their diet, the drug usage rate and exercise rate have been improved
significantly, complication rate have been decreased and the clinical effect is
remarkable. CONCLUSION: the application of Continuing Nursing in the nursing
service for diabetic patients, which could effectively improve living quality and
clinical symptoms of patients, deserves to be popularized.
PMID- 28412685
TI - TCM comprehensive nursing intervention to pathological jaundice on neonate.
AB - Pathological Jaundice on neonate differs from that of physiologic jaundice. They
perform differently on clinical cases, which is an effective way to distinguish
them. There are many causes for pathological jaundice, common ones include
hemolytic jaundice, infectious jaundice, obstructive jaundice, breast-feeding
jaundice, etc. Clinically proven that pathological jaundices has significant
differences in symptoms. This brings problems to its treatment and nursing. In
recent years, TCM comprehensive nursing shows great results in treating process.
Therefore, this paper take 2000 cases to make a thorough analysis for the actual
clinical effects of TCM comprehensive nursing on pathological jaundice on
neonate.
PMID- 28412686
TI - Analysis of application of docetaxel combined therapy scheme in treating advanced
head and neck neoplasm.
AB - Docetaxel is a semi-synthetic taxoid anti-cancer drug, which can basically freeze
intracellular skeleton that is composed of microtubules, so as to inhibit cell
division. Under normal condition, Docetaxel can make microtubule in a cell cycle
follow the rule of first polymerization and then depolymerization. Moreover,
docetaxel can further promote the microtubule polymerization while inhibiting
cell depolymerization, so as to prevent cells division, lead to cancer cells
death, and improve the therapeutic efficiency of tumor and cancer. However, as a
newly developed drug, docetaxel's specific clinical effect has not been fully
verified yet. Therefore, in this research, 2000 patients of advanced head and
neck neoplasm were selected as research objects, which were treated with
docetaxel combined with DDP and fluorouracil. By observing indexes such as
patient's condition, complication condition, and life quality, the clinical
effect of docetaxel combined therapy scheme in treating head and neck neoplasm
was analyzed. Results show that such therapy scheme is of sound therapeutic
effect and high application value.
PMID- 28412687
TI - Application of tegafur gimer, docetaxel and carboplatin in head and neck squamous
cell carcinoma therapy.
AB - Squamous cell carcinoma, in the clinical manifestation, is a form of cancer
derived from lesions of keratinocytes of epidermis or accessories such as
sebaceous ducts, hair follicles, sweat glands, etc. The disease is more common in
older men, with prone locations at patients' scalp, face, neck and arms and other
exposed parts. Head and neck squamous cell carcinoma (HNSCC) causes a serious
impact on patients' daily life, making patients suffer from double blow in mental
and physical aspects and reducing patients' life quality. To find effective
treatment method for HNSCC, our hospital studies clinical effects of combination
therapy of tegafur gimer, docetaxel and carboplatin for the disease. By way of
grouping research, therapeutic effect of such treatment and adverse reactions
were assessed and analyzed. The study clearly and fully confirms effectiveness of
combination therapy of tegafur gimer, docetaxel and carboplatin for HNSCC.
PMID- 28412688
TI - Clinical research of treating tuberculous respiratory failure by sequential
mechanical ventilation.
AB - Tuberculosis is kind of common chronic infectious disease, of which the
pathogenic bacterium is mainly Mycobacterium tuberculosis (MTB). One who is
suffering severe tuberculosis may be ended with cardio-pulmonary function damage
or cardio-pulmonary failure. This disease is of higher risks of complications or
even high death rate, which is seriously challenging people's health and life.
When a tuberculosis patient is accompanied with respiratory failure, which means
the disease has developed into the late stage, on this occasion the optimal
treatment program is to use mechanical ventilation to improve the respiratory
failure condition. This research mainly explored the clinical effect of treatment
of tuberculous respiratory failure by sequential mechanical ventilation, and
observed clinical treatment effect, patients' basic conditions, condition of VAP
and deterioration-in-death condition after sequential mechanical ventilation.
PMID- 28412689
TI - Simple, rapid and highly sensitive HPLC method for measurement of Lamotrigine in
human plasma and its clinical applications.
AB - Spikes in Lamotrigine concentrations levels and associated clinical toxicity may
occur unpredictably. This study describes the development and validation of a
simple, more rapid, highly sensitive and economical method for measuring
Lamotrigine (LTG) concentration levels in human plasma using HPLC-UV and its
clinical applications. Analyte from plasma was extracted with methanol (protein
precipitation) and separated on the analytical column Diamonsil C18 (150mm*4.6mm,
5MUm) Waters-Milford, MA, United States. Mixture of 0.1% Trifluoroacetate and
Methanol used as mobile phase in a 59:41 volume/volume mixture with an isocratic
flow rate of 1.5 ml/min and wavelength was adjusted to 260nm. Standard curve of
lamotrigine showed good linearity over the range of 1.0-50MUg/mL (r2=0.9961) and
LLOQ was 1.0MUg/ml. The Specificity, Recovery, Accuracy, Stability, Robustness
and RSDs for both intraday and interday precision were within acceptable limits.
The highly sensitive HPLC assay for determination of LTG in human plasma was
demonstrated, validated and applied in Therapeutic Drug Monitoring (TDM) of sixty
seven epilepsy patients who were using LTG. The proposed method can be easily
applied in routine Therapeutic monitoring of LTG, Besides TDM, stated method can
be also very useful for Bioequivalence studies, Pharmacovigilance and
Pharmacokinetics studies.
PMID- 28412690
TI - Epidemiological characteristics and clinical features of sporadic viral hepatitis
E (HEV).
AB - OBJECTIVE: The study aims to analyze the epidemiological characteristics and
clinical features of sporadic viral hepatitis E. METHODS: The 1,000 cases of
sporadic viral hepatitis E patients treated in 20 hospitals from May 2013 to May
2016 were selected as research subjects, with their clinical data retrospectively
analyzed. RESULTS: (1) Epidemiological characteristics: Seen from the disease
time, the 1,000 patients have morbidity throughout the year, but morbidity in hot
and rainy summer is significantly higher than other seasons, there exists
statistically difference in comparison between the groups (P<0.05); sporadic
viral hepatitis E has no family aggregation; male morbidity is greater than
female. In the study, there were male 782 cases, 218 female cases, with
male/female ratio at 3.6: 1; morbidity was 13.7% (137/1000) for patients under
18, 62.9% (629/1000) for patients aged 18-60, 23.4% (234/1000) for patients over
60; there were 692 cases of simplex hepatitis E (simplex infection), 308 cases of
hepatitis E complicated with chronic liver disease (super infection), of which,
complicated viral hepatitis B took up the majority. (2) Clinical features: In the
early stage, patients had symptoms of fever, stuffy nose, sore throat; 784
(78.4%) patients had jaundice during illness; 527 (52.7%) patients had loss of
appetite, nausea and other gastrointestinal symptoms; ALT, AST of patients with
hepatitis E plus posthepatitic cirrhosis were significantly lower than patients
with simplex infection (all P<0.01); total bilirubin in patients over 60 was
significantly higher than that of young and middle-aged patients, statistical
difference in statistical analysis was (P <0.05); in the study, 274(27.4%)
patients had complications, complication probability of patients aged over 60 was
higher than young and middle-aged patients, difference comparison was
statistically significant (P<0.05); complication probability of super infected
patients was higher than those with simplex infection (P<0.01). All the patients
underwent liver protection, jaundice removal and other symptomatic treatments,
achieving good treatment effect: 315 cases were cured, 678 cases had improved
condition, 7 cases died. CONCLUSION: There exists obvious correlation between
morbidity of sporadic viral hepatitis E and season, gender and age; once sicken,
one needs to take early symptomatic treatment, to avoid more severe damage to
liver function.
PMID- 28412691
TI - Clinical effect of treatment on elderly chronic obstructive pulmonary disease
combined with pulmonary tuberculosis.
AB - OBJECTIVE: To explore and analyze the clinical therapeutic schedule of elderly
chronic obstructive pulmonary disease combined with pulmonary tuberculosis.
METHOD: This clinical research analysis chooses the 2000 patients suffered
elderly chronic obstructive pulmonary disease combined with pulmonary
tuberculosis treated in the hospital during June of 2014 and June of 2015 as the
object of observation. These 2000 cases are randomly divided into experimental
group and control group. The patients in the control group are treated with the
common method; based on the common method, those in the experimental group are
treated with the atomization inhalation treatment of compound ipratropium bromide
and budesonide and have rifampicin. The clinical effects of two groups are
observed and contracted. RESULTS: The clinical treatment, CRP and other clinical
evaluation indexes of experimental group are superior to the control group
(P<0.05). There are significant differences between two groups with the
statistical significance. CONCLUSION: The atomization inhalation treatment of
compound ipratropium bromide and budesonide and rifampicin are implied into the
elderly chronic obstructive pulmonary disease combined with pulmonary
tuberculosis that can remarkably improve the effect of clinical treatment has
higher clinical promotional value.
PMID- 28412692
TI - Review-Research on the physical training model of human body based on HQ.
AB - Health quotient (HQ) is the newest health culture and concept in the 21st
century, and the analysis of the human body sports model is not enough mature at
present, what's more, the purpose of this paper is to study the integration of
the two subjects the health quotient and the sport model. This paper draws the
conclusion that physical training and education in colleges and universities can
improve the health quotient, and it will make students possess a more healthy
body and mind. Then through a new rigid body model of sports to simulate the
human physical exercise. After that this paper has an in-depth study on the
dynamic model of the human body movement on the basis of establishing the matrix
and equation. The simulation results of the human body bicycle riding and pole
throwing show that the human body joint movement simulation can be realized and
it has a certain operability as well. By means of such simulated calculation, we
can come to a conclusion that the movement of the ankle joint, knee joint and hip
joint's motion law and real motion are basically the same. So it further verify
the accuracy of the motion model, which lay the foundation of other research
movement model, also, the study of the movement model is an important method in
the study of human health in the future.
PMID- 28412694
TI - The sting.
PMID- 28412693
TI - Feeding Angptl4-/- mice trans fat promotes foam cell formation in mesenteric
lymph nodes without leading to ascites.
AB - Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting
LPL. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces the risk
of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic
management of dyslipidemia and atherosclerosis is hampered by the observation
that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation
in the mesenteric lymph nodes (MLNs). In mice these pathological events
exclusively unfold upon feeding a high saturated FA diet and are followed by an
ultimately lethal pro-inflammatory response and chylous ascites. Here, we show
that Angptl4-/- mice fed a diet rich in trans FAs develop numerous lipid-filled
giant cells in their MLNs, yet do not have elevated serum amyloid and
haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a
saturated FA-rich diet. In RAW264.7 macrophages, the saturated FA, palmitate,
markedly increased markers of inflammation and the unfolded protein response,
whereas the trans-unsaturated elaidate and the cis-unsaturated oleate had the
opposite effect. In conclusion, trans and saturated FAs have very distinct
biological effects in macrophages. Furthermore, lipid accumulation in MLNs is
uncoupled from activation of an acute-phase response and chylous ascites,
suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.
PMID- 28412696
TI - PDGF-D is a ligand for NRP1.
PMID- 28412697
TI - Sema3A signalling requires CRMP1 and Nav1.7.
PMID- 28412698
TI - PRODH-ing senescence along.
PMID- 28412699
TI - Neural activity and synaptic pH.
PMID- 28412700
TI - Takayasu Arteritis and Spondyloarthritis: Coincidence or Association? A Study of
14 Cases.
AB - OBJECTIVE: Spondyloarthritis (SpA) and Takayasu arteritis (TA) are 2 chronic
inflammatory diseases; their coexistence in a single patient is uncommon. The
aims of our study were to describe clinical features of patients having SpA
associated with TA and to identify some characteristics of the types of patients
with SpA associated with TA. We also analyzed treatments used in this context.
METHODS: This French multicenter retrospective survey called for observations on
behalf of the Club Rhumatismes et Inflammations, with a standardized
questionnaire established by the investigators. RESULTS: We included 14 patients
(women: 10/14; median age at SpA diagnosis: 43.5 yrs, ranging from 19 to 63).
Subtypes of SpA were ankylosing spondylitis (n = 11), psoriatic arthritis (n =
2), and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (n = 1).
HLA-B27 was positive in 3 cases, negative in 9, and unknown in 2. SpA was
diagnosed before TA in 13 cases. Imaging findings compatible with the diagnosis
of TA were found with computed tomography (11/14) and/or Doppler ultrasound
(10/14). Laboratory tests showed increased acute-phase reactants in all cases (C
reactive protein >= 25 mg/l in 71% of the cases). All patients except 1 received
corticosteroids and 7 were treated with anti-tumor necrosis factor (anti-TNF).
CONCLUSION: Association of SpA and TA is rare but probably not coincidental.
Peripheral pulse palpation and vascular auscultation should be systematic and are
the first indicators of TA in patients with SpA. Moreover, increased acute-phase
reactants during SpA followup should lead to search for TA. Finally, there are
therapeutic implications because anti-TNF are efficient in SpA and might be
efficient in TA.
PMID- 28412701
TI - Association Between Medications and Herpes Zoster in Japanese Patients with
Rheumatoid Arthritis: A 5-year Prospective Cohort Study.
AB - OBJECTIVE: To investigate the association between medications and herpes zoster
(HZ) in patients with rheumatoid arthritis (RA) given biological disease
modifying antirheumatic drugs (bDMARD) or conventional synthetic DMARD in the
clinical setting during 5 years using the Registry of Japanese Rheumatoid
Arthritis Patients on Biologics for Longterm Safety (REAL) database. METHODS: We
calculated the crude incidence rate (IR) of HZ treated with systemic antiviral
medications in 1987 patients from the REAL database. To estimate the association
between HZ and medications, a nested case control study was performed with 1:5
case-control pairs matched for age, sex, observation start year, and comorbidity
(HZ case group, n = 43; control group, n = 214). We calculated OR and 95% CI of
the use of bDMARD, methotrexate (MTX), and corticosteroids for the occurrence of
HZ using a conditional logistic regression analysis. RESULTS: The median patient
age was 60.0 years, female proportion was 81.5%, and median disease duration was
6.0 years. The crude IR (95% CI) of HZ was 6.66 (4.92-8.83)/1000 person-years.
The OR (95% CI) of medication use were 2.28 (1.09-4.76) for tumor necrosis factor
inhibitor (TNFi) and 1.13 (1.03-1.23) for oral corticosteroids dosage (per 1 mg
prednisolone increment), both of which were significantly elevated. The OR of non
TNFi and MTX usage were not elevated. CONCLUSION: TNFi use and higher
corticosteroids dosage were significantly associated with HZ in Japanese patients
with RA in the clinical setting.
PMID- 28412702
TI - Case-control Study on Dactylitis, Enthesitis, and Anterior Uveitis in
Spondyloarthritis Associated with Inflammatory Bowel Diseases: Role of Coexistent
Psoriasis.
AB - OBJECTIVE: To evaluate the frequency of dactylitis, enthesitis, and anterior
uveitis (AU) in spondyloarthritis (SpA) associated with inflammatory bowel
disease (IBD-SpA) compared with other SpA, and to assess the role of associated
psoriasis in the occurrence of dactylitis and enthesitis. METHODS: In a 12-month
case-control study, the frequency of dactylitis and enthesitis in 29 patients
with ulcerative colitis (UC) and 59 with Crohn disease (CD) who satisfied the
Spondyloarthritis international Society criteria for axial or peripheral SpA was
compared with 176 controls, including 97 (55.1%) with psoriatic arthritis (PsA),
47 (26.7%) with ankylosing spondylitis (AS), and 32 (18.2%) with nonradiographic
axial SpA (nr-axSpA). The occurrence of these features in IBD-SpA with and
without psoriasis was also evaluated. RESULTS: Axial, peripheral, or mixed
involvement was observed in 46 (52%), 29 (33%), and 13 (15%) patients,
respectively; and 14/88 (16%) had psoriasis. Dactylitis was recorded in 4/88
patients (4.5%) with IBD-SpA and in 30 controls (17.4%; p = 0.008), enthesitis in
16 cases (18.1%) and in 78/176 controls (44.3%; p < 0.001), and AU in 3 patients
(3.4%) with IBD-SpA and in 26 controls (14.7%; p = 0.01). No significant
differences were found between patients with UC-SpA and those with CD-SpA.
Dactylitis and enthesitis were significantly more common in patients with IBD-SpA
who also had psoriasis compared to those without skin disease (p = 0.009 and
0.003, respectively). CONCLUSION: Dactylitis, enthesitis, and AU are
significantly less frequent in IBD-SpA compared with other types of SpA. Given
the frequent association of psoriasis and IBD, overlooking coexistent skin
disease may lead to overestimating the frequency of these features.
PMID- 28412703
TI - Self-reported Diagnosis of Rheumatoid Arthritis or Ankylosing Spondylitis Has Low
Accuracy: Data from the Nord-Trondelag Health Study.
AB - OBJECTIVE: Self-reported diagnoses of inflammatory arthritis are not accurate.
The primary study aim was to ascertain self-reported diagnoses of rheumatoid
arthritis (RA) and ankylosing spondylitis (AS) in the Norwegian population-based
Nord-Trondelag Health Study (HUNT) using hospital case files. The secondary aim
was to provide updated estimates of the prevalence and incidence of RA and AS.
METHODS: All inhabitants >= 20 years old from the county of Nord-Trondelag were
invited. Data from 70,805 unique participants from HUNT2 (1995-1997) and HUNT3
(2006-2008) were included. For participants who self-reported RA or AS, case
files from all 3 hospitals in the catchment area were evaluated using
standardized diagnostic criteria. RESULTS: Of 2703 self-reported cases of RA,
19.1% were verified in hospital files. Of 1064 self-reported cases of AS, 15.8%
were verified. Of 259 cases self-reporting both RA and AS, 8.1% had RA and 5.4%
had AS. Overall, a self-report of 1 or both diagnoses could not be verified in
82.1%, including 22.8% with insufficient information or no case file. The
prevalence of RA was 768 (95% CI 705-835) per 100,000. The incidence of RA from
HUNT2 to HUNT3 was 0.48 (0.41-0.56) per 1000 per year. The prevalence of AS was
264 (228-305) per 100,000. The incidence of AS from HUNT2 to HUNT3 was 0.19 (0.15
0.24) per 1000 per year. CONCLUSION: Self-reported diagnoses of RA and AS are
often false-positive. The prevalence and incidence of RA were comparable to
reports from similar populations. The incidence of AS was higher than previously
reported in a mixed population from Norway.
PMID- 28412704
TI - Structural Validity of the Rheumatology Attitudes Index in Systemic Sclerosis:
Analysis from the UCLA Scleroderma Quality of Life Study.
AB - OBJECTIVE: To evaluate the structural validity of the Rheumatology Attitudes
Index (RAI), a widely used measure of rheumatic disease-related helplessness in
patients with systemic sclerosis (SSc). METHODS: Patients with physician
confirmed SSc from the University of California, Los Angeles (UCLA) Scleroderma
Quality of Life Study (n = 208) received clinical examinations and completed self
report questionnaires. The structural validity of the RAI was examined through
confirmatory and exploratory factor analysis (CFA/EFA). RESULTS: A tenable factor
structure was not identified through CFA or EFA. CONCLUSION: The present
structural analysis did not support the use of the RAI with SSc patients.
PMID- 28412705
TI - Interferon-alpha for Induction and Maintenance of Remission in Eosinophilic
Granulomatosis with Polyangiitis: A Single-center Retrospective Observational
Cohort Study.
AB - OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized
by frequent relapses following induction therapy. Interferon-alpha (IFN-alpha)
can reverse the underlying Th2-driven immune response and has successfully
induced remission in previous reports. We undertook this study to investigate its
efficacy and safety in patients with EGPA. METHODS: We conducted a retrospective
monocentric cohort study including 30 patients (16 women) with active EGPA under
IFN-alpha treatment. Primary endpoints were remission induction, occurrence of
relapses, prednisolone (PSL) dosage at time of remission, and adverse events.
Remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of 0.
Pulmonary function tests were recorded at baseline and at time of remission.
Health-related quality of life was analyzed by questionnaire at baseline and
following 12 months of treatment. RESULTS: At baseline, the median BVAS was 6
(interquartile range 4-13.5) and remission or partial response was achieved in
25/30 patients. After initiation of IFN-alpha treatment, the median PSL dosages
could be reduced from 17.5 mg/day at baseline to 5.5 mg/day at time of remission.
Following remission, 17 relapses (5 major) in 16 patients were observed.
Pulmonary function tests improved and the time of hospitalization decreased.
Adverse events at initiation of treatment were common, but mostly transient.
Severe adverse events occurred during treatment in 4 patients (autoimmune
hepatitis, n = 1; drug-induced neuropathy, n = 3). CONCLUSION: IFN-alpha
treatment results in high rate of remission and maintenance in EGPA with
significant reduction in oral corticosteroids, although reversible adverse events
may occur. IFN-alpha represents an alternative therapeutic option in cases of
refractory to standard treatment.
PMID- 28412706
TI - Endocrine Comorbidities in Patients with Psoriatic Arthritis: A Population-based
Case-controlled Study.
AB - OBJECTIVE: To investigate endocrine comorbidities in patients with psoriatic
arthritis (PsA). METHODS: A retrospective, cross-sectional study was performed
with the database of Clalit Health Services, the largest healthcare provider in
Israel, between 2002 and 2014. Patients with PsA were identified and matched by
age and sex to healthy controls. The following morbidities were analyzed:
hypo/hyperthyroidism, hypo/hyperparathyroidism, hyperprolactinemia, Cushing
disease, Addison disease, diabetes insipidus, diabetes mellitus (DM), pituitary
adenoma, acromegaly, and osteoporosis. Descriptive statistics were applied. The
associations between PsA and endocrine comorbidities were analyzed by univariable
and multivariable analysis. RESULTS: The study included 3161 patients with PsA,
53.4% women, mean age 58.4 +/- 15.4 years, and 31,610 controls. Comparative
analyses yielded higher proportion of hypothyroidism (12.7% vs 8.6%, p < 0.0001),
Cushing disease (0.3% vs 0.1%, p < 0.0001), osteoporosis (13.2% vs 9.1%, p <
0.0001), and DM (27.9% vs 20.7%, p < 0.0001) in the PsA group compared with the
control group. In the multivariable regression analysis, the following diseases
were more frequent in the PsA group: hypothyroidism (OR 1.61, 95% CI 1.47-1.81),
DM (OR 1.35, 95% CI 1.18-1.42), Cushing disease (OR 3.96, 95% CI 1.67-9.43), and
osteoporosis (OR 1.56, 95% CI 1.37-1.78). CONCLUSION: PsA is associated with a
high frequency of hypothyroidism, osteoporosis, DM, and Cushing disease.
Awareness of these comorbidities may help physicians provide the optimal medical
care to patients with PsA.
PMID- 28412707
TI - Application of the 2016 EULAR/ACR/PRINTO Classification Criteria for Macrophage
Activation Syndrome in Patients with Adult-onset Still Disease.
AB - OBJECTIVE: To evaluate the clinical significance of the 2016 European League
Against Rheumatism (EULAR)/American College of Rheumatology (ACR)/Pediatric
Rheumatology International Trials Organization (PRINTO) classification criteria
for macrophage activation syndrome (MAS) in patients with adult-onset Still
disease (AOSD). METHODS: We performed a retrospective analysis of patients with
AOSD with fever who were admitted to Severance Hospital between 2005 and 2016.
The patients with AOSD were evaluated for MAS using the 2016 classification
criteria for MAS. Clinical features, laboratory findings, and overall survival
were analyzed. Logistic regression analysis was used to evaluate the factors
associated with in-hospital mortality. RESULTS: Among 64 patients with AOSD, 36
(56.3%) were classified as having MAS. The overall survival rate was
significantly lower in patients with MAS than in those without (67% vs 100%, p <
0.001). Multivariate analysis showed that a low erythrocyte sedimentation rate, a
low albumin level, an increase in ferritin of over 2 folds, and the development
of MAS on admission were significantly associated with mortality in patients with
AOSD. CONCLUSION: The 2016 EULAR/ACR/PRINTO classification criteria for MAS are
potentially useful for the identification of patients with AOSD at high risk for
a poor outcome. Febrile patients with AOSD should be monitored with the 2016
classification criteria for MAS in the early diagnosis and proper treatment of
MAS.
PMID- 28412708
TI - Validity and Reliability of Patient Reported Outcomes Measurement Information
System Computerized Adaptive Tests in Systemic Lupus Erythematosus.
AB - OBJECTIVE: The aims of this study were to assess the construct validity and the
test-retest reliability of Patient Reported Outcomes Measurement Information
System (PROMIS) computerized adaptive tests (CAT) in patients with systemic lupus
erythematosus (SLE). METHODS: Adults with SLE completed the Medical Outcomes
Study Short Form-36, LupusQoL-US version ("legacy instruments"), and 14 selected
PROMIS CAT. Using Spearman correlations, PROMIS CAT were compared with similar
domains measured with legacy instruments. CAT were also correlated with the
Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus
Erythematosus Disease Activity Index (SELENA-SLEDAI) disease activity and the
Systemic Lupus International Collaborating Clinics/American College of
Rheumatology Damage Index (SDI) scores. Test-retest reliability was evaluated
using ICC. RESULTS: There were 204 outpatients with SLE enrolled in the study and
162 completed a retest. PROMIS CAT showed good performance characteristics and
moderate to strong correlations with similar domains in the 2 legacy instruments
(r = -0.49 to 0.86, p < 0.001). However, correlations between PROMIS CAT and the
SELENA-SLEDAI disease activity and SDI were generally weak and statistically
insignificant. PROMIS CAT test-retest ICC were good to excellent, ranging from
0.72 to 0.88. CONCLUSION: To our knowledge, these data are the first to show that
PROMIS CAT are valid and reliable for many SLE-relevant domains. Importantly,
PROMIS scores did not correlate well with physician-derived measures. This
disconnect between objective signs and symptoms and the subjective patient
disease experience underscores the crucial need to integrate patient-reported
outcomes into clinical care to ensure optimal disease management.
PMID- 28412709
TI - The Association of Low Income with Functional Status and Disease Burden in German
Patients with Rheumatoid Arthritis: Results of a Cross-sectional Questionnaire
Survey Based on Claims Data.
AB - OBJECTIVE: To assess the influence of income on self-reported disease and work
productivity outcomes. METHODS: Persons with rheumatoid arthritis (RA) diagnosis
(International Classification of Diseases, 10th ed. codes M05/M06) on health
insurance claims data in at least 2 quarters of 2013 were randomly selected. They
were mailed questionnaires covering RA diagnosis, household income, functional
capacity [Hannover functional status questionnaire (FFbH), 0-100], RA Impact of
Disease questionnaire (RAID; 0-10), self-reported swollen joint count (SJC; 0
48), tender joint count (TJC; 0-50), and effect of RA on work productivity
(change of work, fewer working hours, sick leave, application for disability
pension, and others). Weighted multivariable linear regression models were used
to assess the association between income and disease outcomes. RESULTS: A total
of 1492 persons of working age who confirmed RA diagnosis were available for
analysis. The mean age was 55 years, 82% were women, and 74% were under
rheumatologic care. A total of 27%, 52%, and 21% had a low (< ?1500), medium
(?1500-3200), and high monthly income (> ?3200), respectively. Respondents with
low income had the worst mean FFbH, RAID, SJC, and TJC values. This was confirmed
in the regression model: mean FFbH low versus high income -8.65 (95% CI -9.72 to
7.58), RAID 0.73 (0.59-0.86), and SJC 3.47 (2.86-4.08). Sick leave
(8.7%/3.5%/1.8%) and disability pension (18.1%/9.6%/6.9%) were more frequent in
patients with low versus medium versus high income (p < 0.05). CONCLUSION: The
association of low income with a higher disease burden, more functional
disability, and higher rates of work loss emphasizes the need to focus on these
outcomes when choosing treatment strategies for patients in the lower income
groups.
PMID- 28412710
TI - Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in
Patients with Rheumatoid Arthritis and Inadequate Response to MTX: A Systematic
Literature Review.
AB - OBJECTIVE: For patients with rheumatoid arthritis (RA) who have an inadequate
response to methotrexate (MTX), the relative effectiveness of the combination of
conventional disease-modifying antirheumatic drugs (DMARD) compared with the
combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line
therapy, is uncertain. The aim of this study was to compare the efficacy and
tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX
in patients with RA after MTX failure. METHODS: We performed a systematic search
of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library,
and abstracts from the American College of Rheumatology (ACR) and the European
League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were
included if they were of randomized controlled trials of patients receiving
triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine)
compared with anti-TNF agents plus MTX. Treatment effects were examined by
disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR
response criteria, structural damage by the modified total Sharp score, and
functional disability by the Health Assessment Questionnaire (HAQ). RESULTS: Our
search identified 263 articles; only 5 fulfilled the selection criteria. Analysis
of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti
TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse
events did not differ between treatments. CONCLUSION: In patients with RA in whom
MTX has failed, the addition of a TNF antagonist to MTX may be a valid option,
with better clinical outcomes and better radiographic results in the presence of
poor prognostic factors. In the absence of poor prognostic factors and/or with
contraindications to biologic agents, TT retains its place in the therapeutic
strategy for RA in a currently restricted economic context.
PMID- 28412711
TI - Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A
Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated
with 3 Classes of Intravenous bDMARD.
AB - OBJECTIVE: To examine the rate, risks factors, and consequences of neutropenia
induced by intravenous (IV) biologic disease-modifying antirheumatic drugs
(bDMARD). METHODS: We conducted a retrospective cohort study in 499 patients with
rheumatic diseases treated by IV abatacept (ABA), infliximab (IFX), or
tocilizumab (TCZ). RESULTS: Rheumatoid arthritis (RA) was the most frequent
diagnosis (72%). Fifty-two patients (10.4%) experienced at least 1 episode of
neutropenia. No episodes of grade 4 neutropenia were documented. TCZ was more
frequently related to neutropenia than ABA or IFX (18.6% vs 3.8% and 2.8%,
respectively, p < 0.001). The following factors were identified as predictors of
experiencing neutropenia with IV bDMARD: history of neutropenia with methotrexate
(MTX; synthetic DMARD; OR 1.56, 95% CI 1.17-7.14), concomitant treatment by MTX
(OR 1.21, 95% CI 1.01-2.64), and TCZ treatment (OR 2.72, 95% CI 1.53-9.05).
Patients experiencing a TCZ-induced neutropenia did not show a higher risk of
severe infections; however, this group had a shorter drug survival (9 mos vs 20
mos, p < 0.02) compared with TCZ patients without neutropenia. CONCLUSION: Among
3 different classes of IV bDMARD, TCZ is associated with the higher risk of
neutropenia. No increased frequency of infection episodes was documented in this
group.
PMID- 28412712
TI - Antitumor Necrosis Factor-alpha Therapy Associated with Inflammatory Bowel
Disease: Three Cases and a Systematic Literature Review.
AB - OBJECTIVE: Antitumor necrosis factor-alpha (anti-TNF-alpha) therapy is the most
prescribed biologic agent therapy in rheumatology and gastroenterology. However,
a number of serious side effects have been reported with these drugs. Only a
handful of cases of new-onset inflammatory bowel disease (IBD), mostly in
children diagnosed with juvenile idiopathic arthritis (JIA), have been reported
during anti-TNF-alpha therapy. We present 3 cases of adult IBD following anti-TNF
alpha therapy and a literature review on this topic. METHODS: We searched PubMed
MESH for all relevant terms, papers were reviewed, and patient-specific data were
extracted. Relevant clinical data were calculated and presented. RESULTS: The
PubMed search resulted in 137 articles, of which 11 articles and 4 cited
publications were included in our analysis. We found 53 cases of IBD after anti
TNF-alpha therapy reported in the literature; most of them were case series
collected retrospectively from national databases or studies. Almost all the
patients developed IBD after the introduction of etanercept (ETN); 2 patients
with rheumatoid arthritis were also included. The average age at IBD onset was
17.3 years and the average time from ETN introduction to IBD onset was 27 months
(+/- 24). Gastrointestinal symptoms have been reported as improving or subsiding
in most of the patients after discontinuing ETN. CONCLUSION: Although this
manifestation is not common, it should be taken into consideration as an adverse
effect of ETN. Rheumatologists, and in particular rheumatologists treating adult
patients, should be aware of this possible complication. Further investigation
about the pathogenic process underlying this phenomenon is warranted.
PMID- 28412713
TI - Investigation of feet functions of large ruminants with a decoupled model of
equivalent mechanism.
AB - Cloven hooves of ruminants adapt to diverse terrain, provide propulsive force and
support the whole body during movement in natural environments. To reveal how the
feet ensure terrain adaptability by choosing the proper configurations and
terrain conditions, we model the feet of ruminants as an equivalent mechanism
with flexion-extension and lateral movement decoupled. The upper part of the
equivalent mechanism can flex and extend, while the lower part performs the
lateral movement. Combination of the two parts can adapt to longitudinal slope
(anterior-posterior) and transverse slope (medial-lateral), respectively. When
one of two digits closes laterally, the workspace of the other decreases. The
distal interdigital ligament between two digits limits their motion by elastic
force and stores energy during movement. Differences in elastic energy variation
of the ligament on different transverse slopes are characterized based on the
configurations of two digits and the elastic energy between them. If the upper
one of two symmetric digits is fixed, the foot landing on the grade surface (2
degrees ) shows greater capacity for absorbing energy; otherwise, level ground is
the best choice for ruminants. As for the asymmetric digits, longer lateral
digits enhance the optimal adaptive lateral angle. The asymmetry predisposes the
feet to damage on the hard ground, which indicates soft ground is more suitable.
PMID- 28412715
TI - Non-centralized and functionally localized nervous system of ophiuroids: evidence
from topical anesthetic experiments.
AB - Ophiuroids locomote along the seafloor by coordinated rhythmic movements of multi
segmented arms. The mechanisms by which such coordinated movements are achieved
are a focus of interest from the standpoints of neurobiology and robotics,
because ophiuroids appear to lack a central nervous system that could exert
centralized control over five arms. To explore the underlying mechanism of arm
coordination, we examined the effects of selective anesthesia to various parts of
the body of ophiuroids on locomotion. We observed the following: (1) anesthesia
of the circumoral nerve ring completely blocked the initiation of locomotion;
however, initiation of single arm movement, such as occurs during the retrieval
of food, was unaffected, indicating that the inability to initiate locomotion was
not due to the spread of the anesthetic agent. (2) During locomotion, the
midsegments of the arms periodically made contact with the floor to elevate the
disc. In contrast, the distal segments of the arms were pointed aborally and did
not make contact with the floor. (3) When the midsegments of all arms were
anesthetized, arm movements were rendered completely uncoordinated. In contrast,
even when only one arm was left intact, inter-arm coordination was preserved. (4)
Locomotion was unaffected by anesthesia of the distal arms. (5) A radial nerve
block to the proximal region of an arm abolished coordination among the segments
of that arm, rendering it motionless. These findings indicate that the circumoral
nerve ring and radial nerves play different roles in intra- and inter-arm
coordination in ophiuroids.
PMID- 28412714
TI - Reprogramming towards totipotency is greatly facilitated by synergistic effects
of small molecules.
AB - Animal cloning has been achieved in many species by transplanting differentiated
cell nuclei to unfertilized oocytes. However, the low efficiencies of cloning
have remained an unresolved issue. Here we find that the combination of two small
molecules, trichostatin A (TSA) and vitamin C (VC), under culture condition with
bovine serum albumin deionized by ion-exchange resins, dramatically improves the
cloning efficiency in mice and 15% of cloned embryos develop to term by means of
somatic cell nuclear transfer (SCNT). The improvement was not observed by adding
the non-treated, rather than deionized, bovine serum. RNA-seq analyses of SCNT
embryos at the two-cell stage revealed that the treatment with TSA and VC
resulted in the upregulated expression of previously identified reprogramming
resistant genes. Moreover, the expression of early-embryo-specific retroelements
was upregulated by the TSA and VC treatment. The enhanced gene expression was
relevant to the VC-mediated reduction of histone H3 lysine 9 methylation in SCNT
embryos. Our study thus shows a simply applicable method to greatly improve mouse
cloning efficiency, and furthers our understanding of how somatic nuclei acquire
totipotency.
PMID- 28412716
TI - Tanshinone IIA suppresses the progression of atherosclerosis by inhibiting the
apoptosis of vascular smooth muscle cells and the proliferation and migration of
macrophages induced by ox-LDL.
AB - The profound inhibitory effect of Tanshinone IIA (Tan IIA) on atherosclerosis has
been demonstrated, whereas the latent mechanism is not completely cleared. This
study aimed to investigate the cellular and molecular mechanisms underlying Tan
IIA protecting against atherosclerosis. Oil Red O staining and ELISA assay showed
that Tan IIA suppressed the progress of atherosclerosis and reduced the levels of
inflammatory cytokines in serum of apolipoprotein E deficient (ApoE -/- ) mice.
Flow cytometry assay revealed that Tan IIA inhibited oxidized LDL (ox-LDL)
induced apoptosis of VSMCs. MTT and transwell assay indicated that Tan IIA
suppressed the ox-LDL-stimulated proliferation and migration of RAW264.7 cells.
Moreover, Tan IIA ameliorated inflammatory cytokine upregulation elicited by ox
LDL in RAW264.7 cells. Additionally, Tan IIA inhibited the apoptosis of VSMCs and
decreased the levels of MMP-2, MMP-9 in ApoE-/- mice. In conclusion, our study
demonstrated Tan IIA suppressed the progression of atherosclerosis by inhibiting
vascular inflammation, apoptosis of VSMCs and proliferation and migration of
macrophages induced by ox-LDL.
PMID- 28412717
TI - Fibrinogen determination according to Clauss: commutability assessment of
International and commercial standards and quality control samples.
AB - BACKGROUND: Many clinical laboratories use a clotting rate assay according to
Clauss for the determination of fibrinogen in citrated plasma. The aim of the
present study was to assess the commutability of the current International
Standard for fibrinogen (coded 09/264), three commercial fibrinogen standards,
and 10 freeze-dried plasma quality control samples from various sources. METHODS:
Clotting rate assays according to Clauss were performed on three automated
instruments (Sysmex CA1500, STA-Rack Evolution and ACL-Top 700), using three
commercial thrombin reagents (Siemens, Stago, and Instrumentation Laboratory).
Relationships between the results obtained with the three instruments were
determined with 25 fresh-frozen plasma samples obtained from patients. The
deviations of the assay results obtained with the freeze-dried samples were
compared with the deviations obtained with the fresh-frozen samples, according to
approved CLSI guideline C53A. RESULTS: Freezing and thawing had no influence on
the assay results. There were significant differences in the mean assay results
(fibrinogen, g/L) for the fresh-frozen plasma samples between the three automated
instruments: 2.51 (STA-Rack Evolution), 2.25 (ACL-Top 700) and 2.20 (Sysmex
CA1500). Similar differences were observed for several freeze-dried plasma
samples. Some freeze-dried plasma samples, including the International Standard,
were out of the 95% confidence interval for the relationship between STA-Rack
Evolution and Sysmex CA1500. CONCLUSIONS: Some freeze-dried plasmas including the
international standard for fibrinogen are not commutable among automated
instruments for fibrinogen clotting rate assays according to Clauss. Our results
have consequences for all interested parties in the traceability chain (WHO,
industry, external quality assessment schemes, clinical laboratories).
PMID- 28412718
TI - Prognostic value of total antioxidant capacity to predict functional outcome in
traumatic brain injury patients.
PMID- 28412719
TI - Combined measurement of factor XIII and D-dimer is helpful for differential
diagnosis in patients with suspected pulmonary embolism.
AB - BACKGROUND: D-dimer has been used to rule out pulmonary embolism (PE). Based on
previous reports of decreased concentrations of coagulation factor XIII (FXIII)
in venous thromboembolism, and no change in FXIII concentration in patients with
acute cardiovascular disease, we evaluated the benefit of simultaneously
measuring D-dimer and FXIII concentrations for diagnosing PE. METHODS: In this
prospective single-center study, we enrolled 209 patients initially suspected of
having PE, and measured their D-dimer and FXIII concentrations. Forty-one
patients were diagnosed with PE and 168 with other final diagnoses, including
acute coronary syndrome (ACS); aortic dissection (AD); spontaneous pneumothorax
(SP); other respiratory, heart, digestive and nervous diseases; and uncertain
diagnoses. RESULTS: Patients with PE had significantly higher D-dimer and lower
FXIII concentrations than did patients without PE. Combined D-dimer and FXIII
measurements provided a higher positive predictive value (76.6%) for PE than
single tests, especially in patients with Wells score >4.0 (89.3%). Specifically,
patients with AD or ACS showed higher FXIII concentrations and mean platelet
volumes than did patients with PE or SP, and patients with PE and AD had higher D
dimer concentrations than did other patients. At the thresholds of 69.0% for
FXIII and 1.10 MUg/mL for D-dimer, 123/151 patients (81.5%) with serious diseases
(PE, AD, ACS and SP) were correctly distinguished. CONCLUSIONS: Combined
measurement of D-dimer and FXIII helps distinguish PE from serious diseases with
similar symptoms and appears to relate to increased FXIII release from active
platelets in cardiovascular disease.
PMID- 28412720
TI - Mean hemoglobin concentrations in fasting venous and non-fasting capillary blood
of Cambodian women using a hemoglobinometer and an automated hematology analyzer.
PMID- 28412722
TI - Integrating traditional Chinese medicine into Chinese medical education reform:
issues and challenges.
PMID- 28412721
TI - Are admission procalcitonin levels universal mortality predictors across
different medical emergency patient populations? Results from the multi-national,
prospective, observational TRIAGE study.
AB - BACKGROUND: Procalcitonin (PCT), an inflammatory blood biomarker, is well studied
in infectious diseases. Its prognostic value in unselected emergency department
(ED) patients remains yet undefined. Herein, we investigated association of
admission PCT levels and mortality in a large, international-multicenter ED
patient cohort. METHODS: We prospectively enrolled 6970 unselected, consecutive,
adult, medical patients seeking ED care in three tertiary-care hospitals in
Switzerland, France and the USA. We used multivariable logistic regression models
to examine association of admission PCT levels (as a continuous predictor and
across cut-offs) and 30-day mortality. We also investigated subgroup effects by
main diagnosis, comorbidities and clinical features at presentation. RESULTS:
During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased
stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%,
13% to 15%, respectively. This association was also confirmed in a fully-adjusted
model including age, gender, main symptom, main diagnosis and vital parameters on
admission. Receiver operating characteristic (ROC) curve analysis showed that PCT
differentiated well between survivors and non-survivors in the overall cohort
(area under ROC curve [AUC] 0.75) with best results for patient with metabolic
(AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved
the prognostic accuracy of the quick sequential organ failure assessment (qSOFA)
score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other
secondary endpoints including intensive care unit (ICU) admission and hospital
readmission. CONCLUSIONS: In this large and heterogenous medical ED patient
cohort, admission PCT was a strong and independent outcome predictor for 30-day
mortality across different medical diagnoses independent of underlying infection.
PCT may help to improve risk stratification in unselected medical ED patients.
PMID- 28412723
TI - Can video game dynamics identify orthopaedic surgery residents who will succeed
in training?
PMID- 28412724
TI - The quality of the educational environment in a medical college in Saudi Arabia.
AB - Objectives: The study aimed to examine the quality of the educational environment
in the Faculty of Medicine, University of Tabuk, Saudi Arabia, and to compare
between male and female students using the Dundee Ready Educational Environment
Measure (DREEM). Methods: We utilized a cross-sectional survey design.
Participants were 221 medical students (96 males and 125 females) from all
classes (1st to 6th year). Each participant responded to a translated version of
the DREEM questionnaire that measures five domains: students' perception of
learning (SPL), students' perception of teachers (SPT), students' academic self
perception (SASP), students' perception of atmosphere (SPA), and students' social
self-perception (SSSP). Numerical differences between male and female students
were analyzed using the Student's t-test. Results: The global average score of
female students was significantly higher (105.0+/-22.9, 53% of maximum score)
than male students (98.3+/-24.3, 49% of maximum score; t(219)= -2.119, p= 0.035).
The major gender difference was found in the SPT domain, with a higher score in
the females (60%) compared to the male (50%) cohort (t (219)= -5.519, p = 0.000).
Differences in the other domains were statistically insignificant. Out of the 50
DREEM items, the items that need attention were 32 and 23 on the male and the
female sides respectively. Conclusions: The perception of the educational
environment by the female students is significantly better than male students.
The study provides valuable information about many educational problems that need
attention. DREEM-based surveys are highly recommended for periodic monitoring of
the educational environment.
PMID- 28412725
TI - Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk
breast cancers as reliably as genomic markers.
AB - BACKGROUND: The purpose of this study was to test whether immunohistochemical
(IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67)
predict similar numbers of patients with favorable prognoses as genomic markers.
RESULTS: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67
levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post
Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate
signature(GSS) (66.7%: 20/30), but the difference in predictive power was not
significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2)
and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly
downregulated after therapy (P < 0.001 and 0.041, respectively). MATERIALS AND
METHODS: Core needle biopsy specimens of primary breast cancer were collected at
Okayama University Hospital from hormone receptor-positive and human epidermal
growth factor 2-negative patients that subsequently received two weeks of
neoadjuvant hormone therapy. Paired post-treatment specimens from surgical
samples were also collected. IHC Ki67 levels and GSS were compared between pre-
and post-hormone treatment samples. Changes of gene expression pattern in short
term hormone therapy were also assessed. CONCLUSIONS: IHC based post-Ki67 levels
may have distinct predictive power compared with the naive IHC Ki67. Future
studies with larger cohorts and longer follow-up periods may be needed to
validate our results.
PMID- 28412726
TI - Inhaled corticosteroids have a protective effect against lung cancer in female
patients with chronic obstructive pulmonary disease: a nationwide population
based cohort study.
AB - Whether the use of inhaled corticosteroids (ICS) protects patients with chronic
obstructive pulmonary disease (COPD) from lung cancer remains undetermined. In
this retrospective nationwide population-based cohort study, we extracted data of
13,686 female COPD patients (ICS users, n = 1,290, ICS non-users, n = 12,396)
diagnosed between 1997 and 2009 from the Taiwan's National Health Insurance
database. These patients were followed-up until 2011, and lung cancer incidence
was determined. Cox regression analysis was used to estimate hazard ratios (HRs)
for lung cancer incidence. The time to lung cancer diagnosis was significantly
different between ICS users and non-users (10.75 vs. 9.68 years, P < 0.001). Per
100,000 person-years, the lung cancer incidence rate was 235.92 for non-users and
158.67 for users [HR = 0.70 (95% confidence interval {CI}: 0.46-1.09)]. After
adjusting for patients' age, income, and comorbidities, a cumulative ICS dose >
39.48 mg was significantly associated with a lower risk of lung cancer [ICS users
> 39.48 mg, HR = 0.45 (95% CI: 0.21-0.96)]. Age >= 60 years, pneumonia, diabetes
mellitus, and hypertension decreased lung cancer risk, whereas pulmonary
tuberculosis increased the risk. Our results suggest that ICS have a potential
role in lung cancer prevention among female COPD patients.
PMID- 28412727
TI - ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid
leukemia.
AB - Zinc finger protein 521 (ZNF521) is a multiple zinc finger transcription factor
and a strong candidate as regulator of hematopoietic stem cell homeostasis.
Recently, independent gene expression profile studies have evidenced a positive
correlation between ZNF521 mRNA overexpression and MLL-rearranged acute myeloid
leukemia (AML), leaving open the question on the role of ZNF521 in this subtype
of leukemia. In this study, we sought to analyze the effect of ZNF521 depletion
on MLL-rearranged AML cell lines and MLL-AF9 xenograft primary cells. Knockdown
of ZNF521 with short-hairpin RNA (shRNA) led to decreased leukemia proliferation,
reduced colony formation and caused cell cycle arrest in MLL-rearranged AML cell
lines. Importantly, we showed that loss of ZNF521 substantially caused
differentiation of both MLL-rearranged cell lines and primary cells. Moreover,
gene profile analysis in ZNF521-silenced THP-1 cells revealed a loss of MLL-AF9
directed leukemic signature and an increase of the differentiation program.
Finally, we determined that both MLL-AF9 and MLL-ENL fusion proteins directly
interacted with ZNF521 promoter activating its transcription. In conclusion, our
findings identify ZNF521 as a critical effector of MLL fusion proteins in
blocking myeloid differentiation and highlight ZNF521 as a potential therapeutic
target for this subtype of leukemia.
PMID- 28412728
TI - Increased reactive oxygen species levels cause ER stress and cytotoxicity in
andrographolide treated colon cancer cells.
AB - Chemotherapy continues to play an essential role in the management of many
cancers including colon cancer, the third leading cause of death due to cancer in
the United States. Many naturally occurring plant compounds have been
demonstrated to possess anti-cancer cell activity and have the potential to
supplement existing chemotherapy strategies. The plant metabolite andrographolide
induces cell death in cancer cells and apoptosis is dependent upon the induction
of endoplasmic reticulum stress (ER stress) leading to the unfolded protein
response (UPR). The goal of the present study was to determine the mechanism by
which andrographolide induces ER stress and to further evaluate its role in
promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used
to demonstrate that andrographolide induces increased ROS levels, corresponding
anti-oxidant response molecules, and reduced mitochondrial membrane potential. No
increases in ROS levels were detected in control colon fibroblast cells.
Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3
apoptosis elements were all inhibited in the presence of the ROS scavenger NAC.
Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also
reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR
levels that are normally suppressed by andrographolide were also expressed at
normal levels in the absence of ROS. These data demonstrate that andrographolide
induces ER stress leading to apoptosis through the induction of ROS and that
elevated ROS also play an important role in down-regulating cell cycle
progression and cell survival pathways as well.
PMID- 28412729
TI - STK31 as novel biomarker of metastatic potential and tumorigenicity of colorectal
cancer.
AB - PURPOSE: Colorectal cancer (CRC) is the fifth most common cause of cancer deaths
in China and fourth worldwide. Metastatic dissemination of primary tumors is
considered main cause for CRC related mortality. The serine-threonine kinase 31
(STK31) gene is a novel cancer testis (CT) antigen. It was found significantly
highly expressed in gastrointestinal cancers. In our study we aimed to analyze
the correlation between STK31 expression patterns and metastasization, tumor
stage and grade in CRC patients. RESULTS: Relative STK31 expression level was
significantly higher in patients with lymph node metastasis. STK31 expression
levels in primary tumorous tissues of metastatic patients were significantly
higher than in ANCTs and in lymph nodes samples, both at the RNA level and the
protein level. MATERIALS AND METHODS: Surgical specimens of cancerous tissues,
paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with
different clinicopathological features were collected. Expression of STK31 was
detected and measured by immunohistochemistry and quantitative real-time
polymerase chain reaction (QRT-PCR). CONCLUSIONS: Our data suggest that STK31
might be a potential biomarker in detecting, monitoring and predicting the
metastatic risk of colorectal cancer.
PMID- 28412730
TI - The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor
response to chemotherapy in chronic lymphocytic leukemia.
AB - The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer
research, in part due to their ability to serve as disease biomarkers. However,
few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We
have identified one particular lncRNA, treRNA, which is overexpressed in CLL B
cells. We measured transcript expression in 144 CLL patient samples and separated
samples into high or low expression of treRNA relative to the overall median. We
found that high expression of treRNA is significantly associated with shorter
time to treatment. High treRNA also correlates with poor prognostic indicators
such as unmutated IGHV and high ZAP70 protein expression. We validated these
initial findings in samples collected in a clinical trial comparing the
nucleoside analog fludarabine alone or in combination with the alkylating agent
cyclophosphamide in untreated CLL samples collected prior to starting therapy
(E2997). High expression of treRNA was independently prognostic for shorter
progression free survival in patients receiving fludarabine plus
cyclophosphamide. Given these results, in order to study the role of treRNA in
DNA damage response we generated a model cell line system where treRNA was over
expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control
line, there was less cell death in OSU-CLL over-expressing treRNA after exposure
to fludarabine and mafosfamide, due in part to a reduction in DNA damage.
Therefore, we suggest that treRNA is a novel biomarker in CLL associated with
aggressive disease and poor response to chemotherapy through enhanced protection
against cytotoxic mediated DNA damage.
PMID- 28412731
TI - C-terminal binding protein-2 promotes cell proliferation and migration in breast
cancer via suppression of p16INK4A.
AB - C-terminal binding protein-2 (CtBP2) enhances cancer proliferation and
metastasis. The role and mechanism of CtBP2 in breast cancer remains to be
elucidated. Western blot and immunochemistry were employed to evaluate the level
of CtBP2 and p16INK4A in breast cancer. Genetic manipulation was used to study
the expression of p16INK4A and its downstream genes regulated by CtBP2.
Functional assays, including colony formation, wound healing, transwell invasion,
anchorage-independent growth assay and a xenograft tumor model were used to
determine the oncogenic role of CtBP2 in breast cancer progression. The
expression of CtBP2 was increased in breast cancer tissues and cell lines. The
expression of p16INK4A were inversely correlated CtBP2 (r2 = 0.43, P < 0.01). The
expression of both CtBP2 and p16INK4A were significantly related to histological
differentiation (P < 0.01 and P = 0.004, respectively) and metastasis (P = 0.046
and 0.047, respectively). The overall survival rate was lower in patients with
increased CtBP2 expression and lower p16INK4A expression. Knockdown of CtBP2
resulted in the activation of p16INK4A and down-regulation of cell cycle
regulators cyclin D, cyclin E and cyclin-dependent kinase 2 and 4. This down
regulation also led to a decreased transition of the G1-S phase in breast cancer
cells. Moreover, gain-of-function experiments showed that CtBP2 suppressed
p16INK4A and matrix metalloproteinase-2, subsequently enhancing the migration in
breast cancer. However, the silence of CtBP2 abrogated this effect. Collectively,
these findings provide insight into the role CtBP2 plays in promoting
proliferation and migration in breast cancer by the inhibition of p16INK4A.
PMID- 28412733
TI - Prevention of tumor seeding during needle biopsy by chemotherapeutic-releasing
gelatin sticks.
AB - Needle biopsy is an indispensable diagnostic tool in obtaining tumor tissue for
diagnostic examination. Tumor cell seeding in the needle track during
percutaneous needle biopsies has been reported for various types of cancers. The
mechanical force of the biopsy both directly displaces the malignant cells and
causes bleeding and fluid movement that can further disseminate cells. To prevent
the risk of tumor cell seeding during biopsy, we developed a gelatin stick loaded
with chemotherapeutics such as doxorubicin (DXR) that was inserted into the
biopsy canal. The gelatin-doxorubicin sticks (GDSs) were created by passively
loading precut gelatin foam strips (Gelfoam) with doxorubicin solution. The dried
GDSs were inserted into the needle track through the sheath during the needle
biopsy and eventually self-absorbed. We showed that this procedure prevented
iatrogenic tumor seeding during needle biopsies in two subcutaneous tumor models.
In an alternative application, using GDSs in intracranial brain tumor
implantation avoided the outgrowth of tumor from the rodent brain, which could
otherwise potentially fuse the tumor with the meninges and distort the results in
therapeutic studies in rodent brain tumor models.
PMID- 28412732
TI - Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as
potential therapeutic agent for gallbladder cancer.
AB - Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with
high invasiveness and poor response to chemotherapy and radiotherapy. New
therapeutic approaches are urgently needed in order to improve survival and
response rates of GBC patients. We screened 130 small molecule inhibitors on a
panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of
the most potent inhibitory drugs across the different lines. We tested the
antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous
preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90
by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG
and GA significantly reduced the expression of HSP90 target proteins, including
EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular
changes were consistent with reduced cell viability and cell migration and
promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro
studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size,
exhibiting a 69.6% reduction in tumor size in the treatment group compared to
control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in
182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%),
moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical
observations strongly suggest that the inhibition of HSP90 function by HSP90
inhibitors is a promising therapeutic strategy for gallbladder cancer that may
benefit from new HSP90 inhibitors currently in development.
PMID- 28412734
TI - Whole genome sequencing of matched tumor, adjacent non-tumor tissues and
corresponding normal blood samples of hepatocellular carcinoma patients revealed
dynamic changes of the mutations profiles during hepatocarcinogenesis.
AB - Hepatocellular carcinoma (HCC) has become the third most deadly disease worldwide
and HBV is the major factor in Asia and Africa. We conducted 9 WGS (whole genome
sequencing) analyses for matched samples of tumor, adjacent non-tumor tissues and
normal blood samples of HCC patients from three HBV positive patients. We then
validated the mutations identified in a larger cohort of 177 HCC patients. We
found that the number of the unique somatic mutations (average of 59,136) in
tumor samples is significantly less than that in adjacent non-tumor tissues
(average 83, 633). We discovered that the TP53 R249S mutation occurred in 7.7% of
the HCC patients, and it was significantly associated with poor diagnosis. In
addition, we found that the L104P mutation in the VCX gene (Variable charge, X
linked) was absent in white blood cell samples, but present at 11.1% frequency in
the adjacent tissues and increased to 14.6% in HCC tissues, suggesting that this
mutation might be a tumor driver gene driving HCC carcinogenesis. Finally, we
identified a TK1-RNU7 fusion, which would result in a deletion of 103 amino acids
from its C-terminal. The frequencies of this fusion event decreased from the
adjacent tissues (29.2%) to the tumors (16.7%), suggesting that a truncated
thymidine Kinase1 (TK1) caused by the fusion event might be deleterious and be
selected against during tumor progression. The three-way comparisons allow the
identification of potential driver mutations of carcinogenesis. Furthermore, our
dataset provides the research community a valuable dataset for identifying
dynamic changes of mutation profiles and driver mutations for HCC.
PMID- 28412735
TI - Glucose deprivation elicits phenotypic plasticity via ZEB1-mediated expression of
NNMT.
AB - Glucose is considered the primary energy source for all cells, and some cancers
are addicted to glucose. Here, we investigated the functional consequences of
chronic glucose deprivation in serous ovarian cancer cells. We found that cells
resistant to glucose starvation (glucose-restricted cells) demonstrated increased
metabolic plasticity that was dependent on NNMT (Nicotinamide N
methyltransferase) expression. We further show that ZEB1 induced NNMT, rendered
cells resistant to glucose deprivation and recapitulated metabolic adaptations
and mesenchymal gene expression observed in glucose-restricted cells. NNMT
depletion reversed metabolic plasticity in glucose-restricted cells and prevented
de novo formation of glucose-restricted colonies. In addition to its role in
glucose independence, we found that NNMT was required for other ZEB1-induced
phenotypes, such as increased migration. NNMT protein levels were also elevated
in metastatic and recurrent tumors compared to matched primary carcinomas, while
normal ovary and fallopian tube tissue had no detectable NNMT expression. Our
studies define a novel ZEB1/NNMT signaling axis, which elicits mesenchymal gene
expression, as well as phenotypic and metabolic plasticity in ovarian cancer
cells upon chronic glucose starvation. Understanding the causes of cancer cell
plasticity is crucial for the development of therapeutic strategies to counter
intratumoral heterogeneity, acquired drug resistance and recurrence in high-grade
serous ovarian cancer (HGSC).
PMID- 28412736
TI - Tumor biology, clinicopathological characteristics and prognosis of screen
detected T1 invasive non-palpable breast cancer in asymptomatic Chinese women
(2001-2014).
AB - BACKGROUND: Mammography screening usually detects low-risk breast cancer in the
western world. However, little is known about the ultrasound and mammography
screen-detected T1 invasive non-palpable breast cancer (NPBC) in asymptomatic
Chinese women. RESULTS: With the increase of tumor size (T1a, b, c), lymph node
positivity (8.7%, 18.3%, 26.0%, p = 0.018), pN (p = 0.028) and TNM stage (p =
0.035) increased accordingly. Tumor size (T1a, b, c) was correlated with high Ki
67 index (defined as >= 14%, 37.9%, 45.8%, 56.2%, p = 0.017), chemotherapy
(20.4%, 35.2%, 57.3%, p < 0.001) and targeted therapy (2.9%, 9.9%, 15.1%, p =
0.008). T1a disease had higher chance of being luminal A and accompanied with
ductal carcinoma in situ (DCIS), while T1c tumor being triple-negative and
without DCIS. The 5-year disease free survival (DFS) of T1a, b, c NPBC were
99.0%, 96.9% and 92.9%, whereas the 5-year overall survival (OS) were 100.0%,
100.0% and 97.9% respectively. There was no significant difference in 5-year DFS
or OS among the T1 NPBC subgroups or subtypes/immunophenotypes. PATIENTS AND
METHODS: From 2001 to 2014, 4,574 screening positive women received biopsies in
Peking Union Medical College (PUMC) Hospital, and 729 NPBC including 437 T1
unilateral invasive NPBC were diagnosed. With a median follow-up time of 32
months (6-163 months), the clinicopathological characteristics, treatment choice,
5-year DFS and OS were compared between T1a, T1b and T1c NPBC. The DFS and OS
prognostic factors were identified. CONCLUSION: Screen-detected T1 invasive NPBC
could be regarded as low-risk cancer in Chinese women. TNM stage and LN
metastasis instead of molecular subtype was identified as the DFS prognostic
factors while radiotherapy as the OS predictor.
PMID- 28412737
TI - Whole-exome sequencing identifies SGCD and ACVRL1 mutations associated with total
anomalous pulmonary venous return (TAPVR) in Chinese population.
AB - As a rare type of Congenital Heart Defects (CHD), the genetic mechanism of Total
Anomalous Pulmonary Venous Return (TAPVR) remains unknown, although previous
studies have revealed potential disease-driving regions/genes. Blood samples
collected from the 6 sporadic TAPVR cases and 81 non-TAPVR controls were
subjected to whole exome sequencing. All detected variations were confirmed by
direct Sanger sequencing. Here, we identified 2 non-synonymous missense
mutations: c.C652T, p.R218W in activin A receptor type II-like 1 (ACVRL1),
c.C717G, p.D239E in sarcoglycan delta (SGCD). Our results offered the landscape
of mutations for TAPVR in Chinese population firstly and are valuable in the
mutation-based pre- and post-natal screening and genetic diagnosis for TAPVR.
PMID- 28412738
TI - Reduced NOV expression correlates with disease progression in colorectal cancer
and is associated with survival, invasion and chemoresistance of cancer cells.
AB - Aberrant expression of nephroblastoma overexpressed (NOV) has been evident in
certain malignancies. In the current study, we aim to investigate the role played
by NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of
359 CRC tissues and 174 normal colorectal tissues. Its impact on CRC cells was
investigated using in vitro NOV knockdown and overexpression models. NOV
transcripts were reduced in the CRC tumours compared with the paired adjacent
normal colorectal tissues (p < 0.01) and was associated with distant metastases.
NOV knockdown resulted in increased cell proliferation and invasion of RKO cells,
whilst an opposite effect was seen in the HT115 NOV over expressing cells. A
positive association between Caspase-3/-8 and NOV was seen in NOV knockdown and
overexpression cell lines which contributed to the survival of serum deprived CRC
cells. Further investigation showed that NOV regulated proliferation, survival
and invasion through the JNK pathway. NOV knockdown in RKO cells reduced the
responsiveness to 5-Fluorouracil treatment, whilst overexpression in HT115 cells
exhibited a contrasting effect. Taken together, NOV is reduced in CRC tumours and
this is associated with disease progression. NOV inhibits the proliferation and
invasion of CRC cells in vitro. Inhibition of proliferation is mediated by a
regulation of Caspase-3/-8, via the JNK pathway, which has potential for
predicting and preventing chemoresistance.
PMID- 28412739
TI - Retinoic acid receptor alpha drives cell cycle progression and is associated with
increased sensitivity to retinoids in T-cell lymphoma.
AB - Peripheral T-cell lymphomas (PTCLs) are aggressive non-Hodgkin lymphomas with
generally poor outcomes following standard therapy. Few candidate therapeutic
targets have been identified to date. Retinoic acid receptor alpha (RARA) is a
transcription factor that modulates cell growth and differentiation in response
to retinoids. While retinoids have been used to treat some cutaneous T-cell
lymphomas (CTCLs), their mechanism of action and the role of RARA in CTCL and
other mature T-cell lymphomas remain poorly understood. After identifying a PTCL
with a RARAR394Q mutation, we sought to characterize the role of RARA in T-cell
lymphoma cells. Overexpressing wild-type RARA or RARAR394Q significantly
increased cell growth in RARAlow cell lines, while RARA knockdown induced G1
arrest and decreased expression of cyclin-dependent kinases CDK2/4/6 in RARAhigh
cells. The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused
dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Genes
down-regulated in transcriptome data were enriched for cell cycle and G1-S
transition. Finally, RARA overexpression augmented chemosensitivity to retinoids.
In conclusion, RARA drives cyclin-dependent kinase expression, G1-S transition,
and cell growth in T-cell lymphoma. Synthetic retinoids inhibit these functions
in a dose-dependent fashion and are most effective in cells with high RARA
expression, indicating RARA may represent a therapeutic target in some PTCLs.
PMID- 28412740
TI - Combination epidermal growth factor receptor variant III peptide-pulsed dendritic
cell vaccine with miR-326 results in enhanced killing on EGFRvIII-positive cells.
AB - The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is
present in approximately one-third of glioblastoma (GBM) patients. It is never
found in normal tissues; therefore, it represents a candidate target for GBM
immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to
represent a target of glioma and is presented by MHC I/II complexes. Dendritic
cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to
precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by
DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to
precisely kill U87-EGFRvIII cells. In addition to inhibiting proliferation and
inducing the apoptosis of U87-EGFRvIII cells, miR-326 also reduced the expression
of TGF-beta1 in the tumour environment, resulting in improved efficacy of T cell
activation and killing via suppressing the SMO/Gli2 axis, which at least
partially reversed the immunosuppressive environment. Furthermore, combining the
EGFRvIII-DC vaccine with miR-326 was more effective in killing U87-EGFRvIII cells
compared with the administration of either one alone. This finding suggested that
a DC-based vaccine combined with miR-326 may induce more powerful anti-tumour
immunity against GBM cells that express a relevant antigen, which provides a
promising approach for GBM immunotherapy.
PMID- 28412741
TI - Opposite effects of GCN5 and PCAF knockdowns on the alternative mechanism of
telomere maintenance.
AB - Cancer cells can use a telomerase-independent mechanism, known as alternative
lengthening of telomeres (ALT), to elongate their telomeres. General control non
derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous
acetyltransferases that are mutually exclusive subunits in SAGA-like complexes.
Here, we reveal that down regulation of GCN5 and PCAF had differential effects on
some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is
present at telomeres and opposes telomere recombination, in contrast to PCAF that
may indirectly favour them in ALT cells.
PMID- 28412742
TI - Association of the long non-coding RNA MALAT1 with the polycomb repressive
complex pathway in T and NK cell lymphoma.
AB - Recently, various long non-coding RNAs (lncRNAs) have been reported to have
significant therapeutic or prognostic value. However, the expression of lncRNAs
has not been investigated in T and NK cell lymphoma. Thus, we evaluated the
biological and prognostic role of lncRNAs related to the polycomb repressive
complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell
lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical
samples and cell lines. High expression of MALAT1 as well as BMI1 was related to
poor prognosis in patients with mature T cell lymphoma. In the tissue samples,
BMI1 expression showed a positive correlation with EZH2, SUZ12, H3K27me3, and
MALAT1. Multiple linear regression analysis showed that BMI1 expression was
independently associated with H3K27me3. Direct binding of MALAT1 to the PRC2
components (EZH2 and SUZ12) was observed in a T cell lymphoma cell line; however,
no direct binding of MALAT1 with H3K27me3 and BMI1 (a PRC1 component) was
observed.In T and NK cell lymphomas, MALAT1 was related to poor prognosis. MALAT1
directly binds to EZH2 and SUZ12, and BMI1 activation may be induced possibly
through H3K27me3.
PMID- 28412743
TI - Autologous transplantation of cytokine-induced killer cells as an adjuvant
therapy for hepatocellular carcinoma in Asia: an update meta-analysis and
systematic review.
AB - BACKGROUND: High recurrence rate after curative treatment is the major problem
for hepatocellular carcinoma (HCC). Cytokine-induced killer cells (CIKs) therapy
was extensively studied among HCC patients. However, the value of CIKs therapy
was controversial. A meta-analysis was performed to investigate the efficacy of
adjuvant CIKs after invasive treatments among HCC patients. METHODS: We searched
online for literatures studying sequential CIKs therapy for HCC patients.
Recurrence-free survival (RFS), progress-free survival (PFS) and overall survival
(OS) were set as the main endpoints. Both overall and subgroup analysis were
accomplished. RESULTS: A total of 12 clinical trials with 1,387 patients were
included. The pooled analysis showed a significant improvement of RFS, PFS and OS
in CIK group (HR 0.56, 95% CI 0.47-0.67, p<0.00001 for RFS; HR 0.53, 95% CI 0.40
0.69, p<0.00001 for PFS; HR 0.59, 95% CI 0.46-0.77, p<0.0001 for OS). The
proportion of CD4+ T cells increased significantly, while CD8+ T cells decreased
significantly after CIKs therapy (WMD 4.07, 95% CI 2.58-5.56, p<0.00001; WMD
2.84, 95% CI -4.67 to -1.01, p=0.002, respectively). No significant differences
of adverse events between CIK and non-CIK group existed. CONCLUSIONS:
Conventionally invasive therapies combined with CIKs therapy could improve the
prognosis of HCC patients, especially for RFS and PFS, with mild side effects.
Optimizing patient selection shall be the direction in future studies.
PMID- 28412744
TI - Mitochondrial VDAC1-based peptides: Attacking oncogenic properties in
glioblastoma.
AB - Glioblastoma multiforme (GBM), a primary brain malignancy characterized by high
morbidity, invasiveness, proliferation, relapse and mortality, is resistant to
chemo- and radiotherapies and lacks effective treatment. GBM tumors undergo
metabolic reprograming and develop anti-apoptotic defenses. We targeted GBM with
a peptide derived from the mitochondrial protein voltage-dependent anion channel
1 (VDAC1), a key component of cell energy, metabolism and apoptosis regulation.
VDAC1-based cell-penetrating peptides perturbed cell energy and metabolic
homeostasis and induced apoptosis in several GBM and GBM-derived stem cell lines.
We found that the peptides simultaneously attacked several oncogenic properties
of human U-87MG cells introduced into sub-cutaneous xenograft mouse model,
inhibiting tumor growth, invasion, and cellular metabolism, stemness and inducing
apoptosis. Peptide-treated tumors showed decreased expression of all tested
metabolism-related enzymes and transporters, and elevated levels of apoptotic
proteins, such as p53, cytochrome c and caspases. Retro-Tf-D-LP4, containing the
human transferrin receptor (TfR)-recognition sequence, crossed the blood-brain
barrier (BBB) via the TfR that is highly expressed in the BBB to strongly inhibit
tumor growth in an intracranial xenograft mouse model. In summary, the VDAC1
based peptides tested here offer a potentially affordable and innovative new
conceptual therapeutic paradigm that might overcome GBM stemness and invasiveness
and reduce relapse rates.
PMID- 28412745
TI - Neutrophil count is associated with myeloid derived suppressor cell level and
presents prognostic value of for hepatocellular carcinoma patients.
AB - Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for
multiple cancers. However, target agents on MDSC have not display promising
efficacy. One of the critical reasons shall be less optimal patient selection. In
the present study, we aimed to identify clinical parameters relevant to MDSC
level in hepatocellular carcinoma (HCC) patients for future MDSC targeted
therapy. In the present study, a series of 55 HCC patients (testing group) and 20
healthy donors were analyzed investigating frequencies of MDSC in peripheral
blood mononuclear cells (PBMC). As a result, we found that MDSC level was
increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p <
0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p <
0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was
positively associated with MDSC level. Then, the prognostic value of the above
predictors was determined in a retrospective database of 255 HCC patients
(validation group). The baseline characteristics of testing and validation group
were similar. Multivariate analysis by Cox regression revealed that neutrophil
count was an independent predictor for overall survival (OS) (p = 0.000, HR
1.065, 95% CI 1.028-1.103), with the rest parameters failed to reach a
significant result. In summary, the present study firstly identified blood
neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And,
patients with higher neutrophil count level might be the optimal patient subgroup
for MDSC targeted therapy.
PMID- 28412746
TI - Kruppel-like factor 4 (KLF4) regulates the miR-183~96~182 cluster under
physiologic and pathologic conditions.
AB - MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that post
transcriptionally control the translation and stability of target mRNAs in a
sequence-dependent manner. MiRNAs are essential for key cellular processes
including proliferation, differentiation, cell death and metabolism, among
others. Consequently, alterations of miRNA expression contribute to developmental
defects and a myriad of diseases.The expression of miRNAs can be altered by
several mechanisms including gene copy number alterations, aberrant DNA
methylation, defects of the miRNA processing machinery or unscheduled expression
of transcription factors. In this work, we sought to analyze the regulation of
the miR-182 cluster, located at the 7q32 locus, which encodes three different
miRNAs that are abundantly expressed in human embryonic stem cells and de
regulated in cancer. We have found that the Kruppel-like factor 4 (KLF4) directly
regulates miR-182 cluster expression in human embryonic stem cells (hESCs) and in
melanoma tumors, in which the miR-182 cluster is highly expressed and has a pro
metastatic role. Furthermore, higher KLF4 expression was found to be associated
with metastatic progression and poor patient outcome. Loss of function
experiments revealed that KLF4 is required for melanoma cell maintenance. These
findings provide new insights into the regulation of the miR-182 cluster
expression and new opportunities for therapeutic intervention in tumors in which
the KLF4-miR-182 cluster axis is deregulated.
PMID- 28412747
TI - Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in
selenium-replete men.
AB - According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast
supplement containing selenium, 200 mcg/day, decreased the incidence of total
cancer, cancers of the prostate, colon and lung, and cancer mortality. The active
agent in the selenized yeast supplement was assumed to be selenomethionine
(SEMET), although the supplement had not been well speciated. The SELECT study,
largely motivated by the NPC trial, enrolling nearly 40 times as many subjects,
showed unequivocally that selenium 200 mcg/day, with selenium in the form of
SEMET, does not protect selenium-replete men against prostate or other major
cancer. The agent tested by SELECT, pure SEMET, could have been different from
the selenized yeast tested in NPC. One of the selenium forms suspected of having
chemopreventive effects, and which may have been present in the NPC agent, is
methyl selenocysteine (MSC). This study, with 29 selenium-replete patients
enrolled in a randomized, double-blind trial, compared the multiple-dose
toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were
on trial for 84 days. No toxicity was observed. Although SEMET supplementation
increased blood selenium concentration more than MSC did, neither form had a more
than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and
glutathione peroxidase(GPX).
PMID- 28412748
TI - Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the
switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal
cancer.
AB - Cancer associated fibroblasts (CAFs) are a crucial cellular component in tumor
microenvironment and could promote tumor progression. CAFs are usually derived
from resident fibroblasts, which undergoing an activated process stimulated by
tumor cells. However, the agents and mechanism driving this switch have not yet
been elucidated. Progranulin (PGRN), a well acknowledged secreted glycoprotein,
could promote proliferation and angiogenesis of colorectal cancer (CRC) cells,
and high expression of PGRN correlated with patient poor prognosis. Whether PGRN
has effects on the function of stromal fibroblasts is unknown. Herein we found
that there was a positive correlation between PGRN expression of CRC cells and
expressions of smooth muscle actin alpha (alpha-SMA) on CAFs in CRC patient
tissues. PGRN/alpha-SMA co-expression was positively correlated with CRC patient
poor prognosis. Co-cultured with CRC cells or human recombinant PGRN (rPGRN), the
expression of Ki67, fibroblast activation protein (FAP) and alpha-SMA in
fibroblasts were all up-regulated significantly, accompanying with elevated
cellular proliferation, migration and contraction. Whilst co-cultured with PGRN
silenced CRC cells, these functions were down-regulated. Studies of the
underlying molecular mechanism demonstrated that either tumor necrosis factor
receptor 2 (TNFR2)/Akt or the extracellular regulated kinase (ERK) signaling
pathway contributed to modulate of Ki67, FAP, and alpha-SMA expression, and
correlated to abilities of proliferation, migration and contraction in
fibroblasts. In conclusion, PGRN plays an important role in activation of CRC
fibroblasts, which may be taken as a prospective target of CRC therapy.
PMID- 28412749
TI - Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular
carcinoma.
AB - Recent studies have demonstrated an oncogenic role of the transcription factor
(TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between
CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c
directly interacts with another TF, YY1, which is also overexpressed in multiple
cancers, including HCC. To evaluate if these proteins are co-regulated in
carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136)
tissues and examined the correlation between their expression and
clinicopathological characteristics of HCC. Receiver operating characteristic
analysis exhibited the validity of CP2c and nuclear YY1 expression as a
diagnostic factor in HCC tissues. High expression of CP2c was significantly
correlated with patient age, and higher histological grade, American Joint
Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC
tissues, whereas high expression of nuclear YY1 was significantly associated with
higher AJCC stage and small vessel invasion. In univariate and multivariate
analyses, high expression of CP2c was significantly correlated with disease free
survival (DFS), indicating that CP2c expression is an independent prognostic
factor for DFS in HCC patients. Patients with high expression of both CP2c and
nuclear YY1 usually had a shorter median survival time and worse DFS prognosis
than other patients, suggesting that combined detection of CP2c and nuclear YY1
is a useful prognostic marker in HCC patients.
PMID- 28412751
TI - Poly (ADP-ribose) polymerase inhibitor, an effective radiosensitizer in lung and
pancreatic cancers.
AB - The development of stereotactic body radiation therapy (SBRT) has revolutionized
radiation therapy for lung cancers and is an emerging treatment option for
pancreatic cancers. However, there are many questions on how to optimize its use
in chemoradiotherapy. The most relevant addition to radiotherapy regimens are
inhibitors of DNA repair and DNA damage response pathways. One such class of
agents are inhibitors of poly (ADP-ribose) polymerase (PARP). In this study we
examined the effects of the PARP inhibitor LT626 in combination with ionizing
radiation in lung and pancreatic cancers. Our study demonstrated that combination
treatment with LT626 and radiation effectively inhibited growth in lung and
pancreatic cancer cell lines, better than individual treatment alone. Combination
treatment also increased expression of gammaH2AX and 53BP1 foci and upregulated
expression of phosphorylated ATM, ATR and their respective kinases. Using in vivo
lung cancer xenograft models we demonstrated that LT626 functioned as an
effective radiosensitizer during fractionated radiation treatment, leading to
significant decrease in tumor burden and doubling the median survival compared to
control group. Overall our in vitro and in vivo studies showed that PARP
inhibitor LT626 acted synergistically with radiation in lung and pancreatic
cancers.
PMID- 28412750
TI - microRNA-302c-3p inhibits renal cell carcinoma cell proliferation by targeting
Grb2-associated binding 2 (Gab2).
AB - The expression and biological function of Grb2-associated binding 2 (Gab2) in
renal cell carcinoma (RCC) cells was tested here. We showed that Gab2 expression
was significantly elevated in human RCC tissues and RCC cells. It was correlated
with over-activation of Akt and downregulation of microRNA-302c-3p ("miR-302c
3p"), a putative Gab2-targeting microRNA. Knockdown of Gab2 inhibited Akt
activation and 786-O RCC cell proliferation. Reversely, forced over-expression of
Gab2 led to Akt hyper-activation to facilitate 786-O cell proliferation.
Exogenous expression of miR-302c caused Gab2 downregulation, Akt inhibition and
786-O cell proliferation inhibition. On the other hand, miR-302c-3p depletion by
expressing its anti-sense ("antagomiR-302c") led to Gab2 upregulation, Akt
activation and increased 786-O cell proliferation. Significantly, miR-302c-3p
failed to affect the proliferation of 786-O cells with shRNA-depleted Gab2.
Together, we suggest that miR-302c-3p depletion in human RCC cells leads to Gab2
over-expression, Akt hyper-activation and cell proliferation.
PMID- 28412752
TI - Clinicopathologic implications of immune classification by PD-L1 expression and
CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer
patients.
AB - We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in
gastric cancer (GC), and categorized into 4 microenvironment immune types.
Immunohistochemistry (PD-L1, CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ
hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed
in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based
adjuvant chemotherapy, and two public genome databases were analyzed for
validation. PD-L1+ was found in 98/392 GCs (25.0%). The proportions of immune
types are as follows: PD-L1+/CD8High, 22.7%; PD-L1-/CD8Low, 22.7%; PD-L1+/CD8Low,
2.3%; PD-L1-/CD8High, 52.3%. PD-L1+/CD8High type accounted for majority of EBV+
and MSI-high (MSI-H) GCs (92.0% and 66.7%, respectively), and genome analysis
from public datasets demonstrated similar pattern. PD-L1-/CD8High showed the best
overall survival (OS) and PD-L1-/CD8Low the worst (P < 0.001). PD-L1 expression
alone was not associated with OS, however, PD-L1-/CD8High type compared to PD
L1+/CD8High was independent favorable prognostic factor of OS by multivariate
analysis (P = 0.042). Adaptation of recent molecular classification based on EBV,
MSI, E-cadherin, and p53 showed no significant survival differences. These
findings support the close relationship between PD-L1/CD8 status based immune
types and EBV+, MSI-H GCs, and their prognostic significance in stage II/III GCs.
PMID- 28412753
TI - Vitamin D increases programmed death receptor-1 expression in Crohn's disease.
AB - BACKGROUND: Vitamin D modulates inflammation in Crohn's disease (CD). Programmed
death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin
D might modulate PD-1 signalling in CD. AIM: To investigate PD-1 expression on T
cell subsets in CD patients treated with vitamin D or placebo. METHODS: We
included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo
and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma
were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and
surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma
levels were measured by ELISA. RESULTS: PD-1 expression upon T cell stimulation
was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19%
(range 10 - 39%) to 29% (11 - 79%)(p = 0.03) compared with placebo-treated
patients. Vitamin D treatment, but not placebo, decreased the expression of the T
cell activation marker CD69 from 42% (31 - 62%) to 33% (19 - 54%)(p = 0.01).
Soluble PD-1 levels were not influenced by vitamin D treatment. CONCLUSIONS:
Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in
response to activation and reduces the CD69 expression in CD patients.
PMID- 28412755
TI - Randomized clinical trial comparing the effects of sevoflurane and propofol on
carbon dioxide embolism during pneumoperitoneum in laparoscopic hepatectomy.
AB - Laparoscopic hepatectomy carries a high risk of gas embolism due to the extensive
hepatic transection plane and large hepatic vena cava. Here, we compared the
influence of inhaled and intravenous anesthetics on gas embolism during
laparoscopic hepatectomy. Fifty patients undergoing laparoscopic hepatectomy were
divided into two groups to receive sevoflurane anesthesia (group S, n = 25) or
intravenous propofol anesthesia (group p, n = 25). During the operation, gas
emboli were detected by transesophageal echocardiography and graded according to
their size. Venous CO2 emboli were detected in all patients, and the embolism
grades did not differ between the two groups. However, the mean embolism episode
duration was longer in group S than group P (51.24+/-23.59 vs. 34.00+/-17.13 sec,
p < 0.05). At the point of the most severe gas embolism, the PTCO2 was higher in
group S than group p (44.00+/-4.47 vs. 41.36+/-2.77 mmHg, p < 0.05), while the
PO2/FiO2 (450.52+/-54.08 vs. 503.80+/-63.18, p < 0.05) and pH values (7.35+/-0.05
vs. 7.38+/-0.02, p < 0.05) were lower in group S than group P. Patients with a
history of abdominal surgery or liver cirrhosis had higher gas embolism grades.
Thus volatile anesthetics may lengthen the duration of embolism episodes and
worsen hemodynamics and pulmonary blood gas exchange during surgery.
PMID- 28412756
TI - Effects of circadian clock genes and environmental factors on cognitive aging in
old adults in a Taiwanese population.
AB - Previous animal studies have indicated associations between circadian clock genes
and cognitive impairment . In this study, we assessed whether 11 circadian
clockgenes are associated with cognitive aging independently and/or through
complex interactions in an old Taiwanese population. We also analyzed the
interactions between environmental factors and these genes in influencing
cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the
Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were
administered to all subjects, and MMSE scores were used to evaluate cognitive
function. Our data showed associations between cognitive aging and single
nucleotide polymorphisms (SNPs) in 4 key circadian clock genes, CLOCK rs3749473
(p = 0.0017), NPAS2 rs17655330 (p = 0.0013), RORA rs13329238 (p = 0.0009), and
RORB rs10781247 (p = 7.9 x 10-5). We also found that interactions between CLOCK
rs3749473, NPAS2 rs17655330, RORA rs13329238, and RORB rs10781247 affected
cognitive aging (p = 0.007). Finally, we investigated the influence of
interactions between CLOCK rs3749473, RORA rs13329238, and RORB rs10781247 with
environmental factors such as alcohol consumption, smoking status, physical
activity, and social support on cognitive aging (p = 0.002 ~ 0.01). Our study
indicates that circadian clock genes such as the CLOCK, NPAS2, RORA, and RORB
genes may contribute to the risk of cognitive aging independently as well as
through gene-gene and gene-environment interactions.
PMID- 28412758
TI - Endoscopic diagnosis of primary anorectal melanoma.
AB - OBJECTIVE: The present study retrospectively analyzed case data from 12 patients
diagnosed with anorectal melanoma, with the purpose of identifying key diagnostic
features at endoscopy. MATERIALS AND METHODS: Images from colonoscopy were
reviewed for all patients in order to establish the endoscopic features of
primary anorectal melanoma. For the patients whose colonoscopic examinations
included endoscopic ultrasound, images were examined to characterize lesions and
the depth of infiltration, the results of which were compared with pathological
findings after operative resection. RESULTS: At colonoscopy, superficial melanin
pigmentation was identified in 10 patients with anorectal melanoma, with
morphology including spots, patches, or sheets of pigmentation. In patients who
underwent endoscopic ultrasound, lesions appeared as masses on the mucosal side
with inhomogeneous or low-level internal echoes or ulcer-type lesions invading
the muscularis propria. Lesions diagnosed as anorectal melanoma also demonstrated
irregular margins and varying degrees of submucosal infiltration. Infiltration
depth of melanoma via endoscopic ultrasound (EUS) was concordant with surgical
pathology results in 100% of patients. CONCLUSION: Colonoscopy combined with
biopsy and subsequent pathological examination can accurately diagnose primary
anorectal melanoma. Moreover, EUS is a reliable tool for assessing the depth of
infiltration of this disease.
PMID- 28412760
TI - Left Ventricular Aneurysm May Not Manifest as Persistent ST Elevation on
Electrocardiogram.
AB - BACKGROUND Electrocardiographic presentations of left ventricle aneurysms are
diverse; however, a persistent ST segment elevation post myocardial infarction is
most commonly reported. CASE REPORT The authors present a case of a 67-year-old
man who presented to the emergency department after three days of chest pain and
was found to have an acute myocardial infarction with an incidental finding of a
left ventricular aneurysm. His surface electrocardiogram, however, demonstrated
only inverted T waves in the precordial leads. He had a very elevated serum
troponin I consistent with an acute myocardial injury which prompted a cardiac
catheterization with angioplasty. Post angioplasty, he had persistent T wave
inversions in the precordial leads. CONCLUSIONS It is important for clinicians to
appreciate that the presence of newly inverted T waves in patients with a late
presentation post myocardial infarction should raise a concern for a possible
left ventricular aneurysm.
PMID- 28412757
TI - Fatty acid metabolism in breast cancer subtypes.
AB - Dysregulation of fatty acid metabolism is recognized as a component of malignant
transformation in many different cancers, including breast; yet the potential for
targeting this pathway for prevention and/or treatment of cancer remains
unrealized. Evidence indicates that proteins involved in both synthesis and
oxidation of fatty acids play a pivotal role in the proliferation, migration and
invasion of breast cancer cells. The following essay summarizes data implicating
specific fatty acid metabolic enzymes in the genesis and progression of breast
cancer, and further categorizes the relevance of specific metabolic pathways to
individual intrinsic molecular subtypes of breast cancer. Based on mRNA
expression data, the less aggressive luminal subtypes appear to rely on a balance
between de novo fatty acid synthesis and oxidation as sources for both biomass
and energy requirements, while basal-like, receptor negative subtypes overexpress
genes involved in the utilization of exogenous fatty acids. With these
differences in mind, treatments may need to be tailored to individual subtypes.
PMID- 28412761
TI - Preoperative Assessment of Hepatocellular Carcinoma with Split-Bolus Combined
Phase Contrast-Enhanced Computed Tomography.
AB - BACKGROUND The aim of this study was to investigate the feasibility of a split
bolus combined phase contrast-enhanced computed tomography protocol in evaluation
of liver vasculature in hepatocellular carcinoma (HCC) patients for the purpose
of surgery guidance. MATERIAL AND METHODS Two groups of patients were recruited
for the study: 24 consecutive cases of HCC who underwent multiphasic CT
examination, and 22 consecutive cases who afterwards underwent split-bolus
combined phase CT examination. The multiphasic protocol included an unenhanced
scan and 3 image acquisitions after contrast injection. The injection of contrast
medium was 440 mgI/kg in a single bolus. The split-bolus combined phase protocol
included unenhanced scan and combined phase. The injection of contrast medium was
440 mgI/kg for the first bolus and 220 mgI/kg for the second bolus. The vascular
delineation was evaluated with Likert scales. The CT values were measured, and
the contrast-to-noise ratio (CNR) was calculated. We also compared the effective
radiation dose (ED) of the 2 protocols. RESULTS All mean CT values were
significantly higher in the split-bolus protocol than in the multiphasic protocol
(all P.05). The ED was significantly lower in the split-bolus protocol,
corresponding to a dose reduction of 66% compared to the multiphasic protocol
(P<.05). The scores of the branches of the hepatic vein in the split-bolus
protocol were not lower than those in the multiphasic protocol. CONCLUSIONS For
the preoperative HCC patients, the split-bolus combined phase CT examination
meets the diagnostic requirement of surgical planning, with approximately 60%
reduction in the radiation dose.
PMID- 28412762
TI - Sleep Deprivation and Late Bedtime Impair Sperm Health Through Increasing
Antisperm Antibody Production: A Prospective Study of 981 Healthy Men.
AB - BACKGROUND The aim of this study was to investigate the effects of sleep duration
and bedtime on sperm health, and the possible mechanism involved. MATERIAL AND
METHODS We randomly divided 981 healthy Chinese men into groups according to
research-set bedtimes (A=8-10 PM, B=after 10 PM, and C=after midnight) and sleep
durations: group 1=<6.0 h (short), group 2=7.0-8.0 h (average), and group 3=>9.0
h (long). Sperm morphology, count, survival, and motility were examined according
to sleep patterns. Antisperm antibody (ASA) production in semen was determined.
RESULTS Sperm counts and their survival rates were lower in the short sleepers as
compared to others within each group (all P<0.01). The lower counts and survival
rates were observed in different bedtimes, with significant differences found
between measurements of C1 vs. A1 and C2 vs. A2 or B2 (all P<0.05 or 0.01). Semen
motility was lower in the short sleepers as compared to the average and long
sleepers (all P<0.01). There were differences in the bedtime-related results
between measurements of C1 vs. A1 or B1 (P<0.05 or 0.01). Additionally, the
population proportion for the ASA-positive participates and incidence of the ASA
expressed population obviously increased in the short sleepers as compared to
others within each group (all P<0.05). CONCLUSIONS Short and long sleep durations
and late bedtime were associated with impaired sperm health in the study cohort,
partly through increasing ASA production in the semen.
PMID- 28412763
TI - Altered expression of SDF-1 and CXCR4 during fracture healing in diabetes
mellitus.
AB - PURPOSE: Diabetes mellitus (DM) is known to impair fracture healing. The purpose
of this study was to elucidate and compare the gene expression patterns and
localization of stromal cell-derived factor 1 (SDF-1) and CXC chemokine receptor
4 (CXCR4) during fracture healing of the femur in rats with and without DM.
METHODS: Closed transverse fractures were created in the femurs of rats equally
divided into a DM group and control group; DM was induced by streptozotocin. At
post-fracture days five, seven, 11, 14, 21 and 28, total RNA was extracted from
the fracture callus and mRNA expression levels of SDF-1 and CXCR4 were measured
by real-time polymerase chain reaction. Localization of SDF-1 and CXCR4 proteins
at the fracture site was determined by immunohistochemistry at days 21 and 28.
RESULTS: SDF-1 expression was significantly lower in the DM group than in the
healthy group on days 21 and 28, and showed a significant difference between days
14 and 21 in the healthy group. There was no significant difference in CXCR4
expression levels between the healthy and DM groups at any time point. On day 21
immunoreactivity of SDF-1 and CXCR4 was detected at the fracture site of the
healthy group but no immunoreactivity was observed in the DM group. On day 28,
immunoreactivity of SDF-1 and CXCR4 was detected at the fracture site in both
groups. CONCLUSION: Gene expression and localization of SDF-1 and CXCR4 was
altered during fracture healing, which may contribute to the impaired fracture
healing in DM.
PMID- 28412764
TI - How Networks of Informal Trails Cause Landscape Level Damage to Vegetation.
AB - When visitors are not constrained to remain on formal trails, informal trail
networks can develop and damage plant communities in protected areas. These
networks can form in areas with low growing vegetation, where formal trails are
limited, where there is limited regulation and where vegetation is slow to
recover once disturbed. To demonstrate the extent of impacts from unregulated
recreational use, we assessed damage to alpine vegetation by hikers and pack
animals in the highest protected area in the southern Hemisphere: Aconcagua Park,
in the Andes. Within the 237 ha area surveyed in the Horcones Valley, over 19 km
of trails were found, nearly all of which (94%) were informal. This network of
trails resulted in the direct loss of 11.5 ha of vegetation and extensive
fragmentation of alpine meadows (21 fragments) and steppe vegetation (68
fragments). When levels of disturbance off these trails were quantified using
rapid visual assessments, 81% of 102 randomly located plots showed evidence of
disturbance, with the severity of disturbance greatest close to trails. As a
result, vegetation in 90% of the Valley has been damaged by visitor use, nearly
all of it from unregulated use. These results highlight the extent to which
informal trails and trampling off-trail can cause landscape damage to areas of
high conservation value, and hence the importance of better regulation of visitor
use. The methodology used for off-trail impact assessment can be easily applied
or adapted for other popular protected areas where trampling off-trail is also an
issue.
PMID- 28412765
TI - Advanced Value Chain Collaboration in Ghana's Cocoa Sector: An Entry Point for
Integrated Landscape Approaches?
AB - Value chain analyses have focused mainly on collaboration between chain actors,
often neglecting collaboration "beyond the chain" with non-chain actors to tackle
food security, poverty and sustainability issues in the landscapes in which these
value chains are embedded. Comparing conventional and advanced value chain
collaborations involving small-scale cocoa farmers in Ghana, this paper analyzes
the merits of a more integrated approach toward value chain collaboration. It
particularly asks whether advanced value chain collaboration targeting cocoa
producing areas potentially offers an entry point for implementing a landscape
approach. The findings detail current chain actors and institutions and show how
advanced value chain collaboration has a greater positive impact than
conventional value chain collaboration on farmers' social, human and natural
capital. The paper concludes that the integrated approach, focus on learning, and
stable relationships with small-scale farmers inherent in advanced value chain
collaboration makes it both more sustainable and effective at the local level
than conventional approaches. However, its scope and the actors' jurisdictional
powers and self-organization are too limited to be the sole tool in negotiating
land use and trade-offs at the landscape level. To evolve as such would require
certification beyond the farm level, partnering with other landscape
stakeholders, and brokering by bridging organizations.
PMID- 28412766
TI - Integrative Governance of Environmental Water in Australia's Murray-Darling
Basin: Evolving Challenges and Emerging Pathways.
AB - Integration, a widely promoted response to the multi-scale complexities of social
environmental sustainability, is diversely and sometimes poorly conceptualized.
In this paper we explore integrative governance, which we define as an iterative
and contextual process for negotiating and advancing the common interest. We
ground this definition in a discussion of institutional factors conditioning
integrative governance of environmental water in Australia's Murray-Darling
Basin. The Murray-Darling Basin is an iconic system of social-ecological
complexity, evocative of large-scale conservation challenges in other developed
arid river basins. Our critical assessment of integrative governance practices in
that context emerges through analysis of interviews with policy participants and
documents pertaining to environmental water management in the tri-state area of
southwestern New South Wales, northwestern Victoria, and the South Australian
Riverland. We identify four linked challenges: (i) decision support for
developing socially robust environmental water management goals, (ii) resource
constraints on adaptive practice, (iii) inter-state differences in participatory
decision-making and devolution of authority, and (iv) representative inclusion in
decision-making. Our appraisal demonstrates these as pivotal challenges for
integrative governance in the common interest. We conclude by offering a
perspective on the potential for supporting integrative governance through the
bridging capacity of Australia's Commonwealth Environmental Water Holder.
PMID- 28412767
TI - Herbage intake and milk yield in Comisana ewes as effect of 4 vs 7 h of grazing
during late lactation.
AB - Thirty-two Comisana ewes at late lactation were used in two trials carried out
during late spring in 2 consecutive years, with the aim to evaluate the effect of
the duration of grazing on herbage intake and performance. In each trial, 16
pluriparous Comisana lactating ewes were equally divided into two groups which
grazed in two separate areas of natural pasture from 11:00 to 15:00 h (group 4H)
or from 10:00 to 17:00 (group 7H). A concentrate mixture (500 g/day) was also
offered to each ewe. The mean maximum temperature was, respectively, 23.5 +/- 3.8
degrees C during experiment 1 and 27.0 +/- 3.1 degrees C during experiment 2.
Probably as a consequence of the differences in climatic conditions, the results
on herbage intake and milk production were different during the two trials.
Herbage dry matter intake was not affected by the duration of grazing during
trial 1, whereas it was significantly lower in 4H group compared to that in 7H
group (0.67 vs 1.02 kg/day; P < 0.001) during trial 2. It could be hypothesised
that while with lower environmental temperature (trial 1), the 4H ewes were able
to reach good intake levels despite grazing during the hottest hours; with higher
temperatures throughout the trial (trial 2), the 4H ewes reduced ingestion. Milk
production was higher in 4H group during trial 1 (778 vs 707 g/day; P = 0.006),
whereas it was not affected by the number of hours of grazing during trial 2,
despite the higher intake levels reached by the 7H group. In conclusion, 3 extra
hours of grazing for ewes at late lactation on a low quality pasture could be
nullified in terms of yield response.
PMID- 28412768
TI - Assessing the dispersive and electrostatic components of the selenium-aromatic
interaction energy by DFT.
AB - Selenium has been increasingly recognized as an important element in biological
systems, which participates in numerous biochemical processes in organisms,
notably in enzyme reactions. Selenium can substitute sulfur of cysteine and
methionine to form their selenium analogues, selenocysteine (Sec) and
selenomethionine (SeM). The nature of amino acid pockets in proteins is dependent
on their composition and thus different non-covalent forces determine the
interactions between selenium of Sec or SeM and other functional groups,
resulting in specific biophysical behavior. The discrimination of selenium toward
sulfur has been reported. In order to elucidate the difference between the nature
of S-pi and Se-pi interactions, we performed extensive DFT calculations of
dispersive and electrostatic contributions of Se-pi interactions in substituted
benzenes/hydrogen selenide (H2Se) complexes. The results are compared with our
earlier reported S-pi calculations, as well as with available experimental data.
Our results show a larger contribution of dispersive interactions in Se-pi
systems than in S-pi ones, which mainly originate from the attraction between Se
and substituent groups. We found that selenium exhibits a strong interaction with
aromatic systems and may thus play a significant role in stabilizing protein
folds and protein-inhibitor complexes. Our findings can also provide molecular
insights for understanding enzymatic specificity discrimination between single
selenium versus a sulfur atom, notwithstanding their very similar chemical
properties.
PMID- 28412769
TI - Applicability of geochemical techniques and artificial sweeteners in
discriminating the anthropogenic sources of chloride in shallow groundwater north
of Toronto, Canada.
AB - Elevated levels of chloride concentration due to anthropogenic activities
including the road salts, septic effluent and agricultural sources are common in
shallow groundwater of the recent glacial deposits north of Toronto, Ontario,
Canada. Identifying suitable techniques for discriminating the source of the
chloride concentration helps to better plan the protection of groundwater in the
area. This paper examines the applicability of geochemical techniques with
emphasis on Panno et al. (Ground Water 44: 176-187, 2006) and Mullaney et al.
(2009) graphical approaches for discriminating the sources of chloride with known
causes of impacts. The results indicated that the graphical methods developed
using Cl-, Br- and/or total nitrogen (N) could identify the combined sources of
road salts and septic systems. However, discriminating between the road salts,
septic effluent or agricultural sources needs to be complemented by other
techniques including the artificial sweeteners and isotope tracers.
PMID- 28412770
TI - Anemia in chronic kidney disease.
AB - Anemia is common and associated with adverse outcomes in children with chronic
kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD
progresses, but impaired production of erythropoietin by failing kidneys is a
central cause. Hepcidin-mediated iron restriction also contributes to anemia by
downregulating both intestinal iron absorption and release of stored iron for
erythropoiesis. The core components of anemia management remain erythropoiesis
stimulating agents (ESA) and iron supplementation, but despite these therapies, a
substantial number of children remain anemic. Although escalating ESA dose to
target higher hemoglobin has been associated with adverse outcomes in adults, no
trials have investigated this association in children, and maintaining hemoglobin
levels in a narrow range with conservative ESA dosing is challenging. Judicious
use of iron supplementation can enhance the response to ESAs, but the iron
storage markers most commonly used in clinical practice have limitations in
distinguishing which patients will benefit most from additional iron. Several
novel anemia therapies, including hypoxia-inducible factor stabilizers, prolyl
hydroxylase inhibitors, and dialysate-delivered iron supplements, have been
developed and may offer options for alternative anemia management. However, the
safety and efficacy of these agents in children with CKD has yet to be assessed.
PMID- 28412771
TI - Drug cue reactivity involves hierarchical instrumental learning: evidence from a
biconditional Pavlovian to instrumental transfer task.
AB - RATIONALE: Drug cue reactivity plays a crucial role in addiction, yet the
underlying mechanisms are poorly understood. According to the binary associative
account, drug stimuli retrieve an expectation of the drug outcome, which, in
turn, elicits the associated drug-seeking response (S-O-R). By contrast,
according to the hierarchical account, drug stimuli retrieve an expectation that
the contingency between the drug-seeking response and the drug outcome is
currently more effective, promoting performance of the drug-seeking response (S:R
O). METHODS: The current study discriminated between these two accounts using a
biconditional Pavlovian-to-instrumental transfer (PIT) task with 128 alcohol
drinkers. A biconditional discrimination was first trained in which two responses
produced alcohol and food outcomes, respectively, and these response-outcome
contingencies were reversed across two discriminative stimuli (SDs). In the PIT
test, alcohol and food cues were compounded with the two SDs to examine their
impact on percent alcohol choice in extinction. RESULTS: It was found that
alcohol and food cues selectively primed choice of the response that earned that
outcome in each SD (p < .001), and this effect was associated with participants'
belief that cues signalled greater effectiveness of that response (p < .0001).
CONCLUSIONS: The alcohol stimulus could not have selectively primed the alcohol
seeking response through binary S-O-R associations because the drug outcome was
equally associated with both responses. Rather, the alcohol stimulus must have
retrieved an expectation that the response-alcohol contingency available in the
current context was more likely to be effective (S:R-O), which primed performance
of the alcohol-seeking response.
PMID- 28412772
TI - Quantitative analysis of external limiting membrane, ellipsoid zone and
interdigitation zone defects in patients with macular holes.
AB - PURPOSE: To investigate the correlation between the length of external limiting
membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) defects and
visual prognosis in patients undergoing macular hole (MH) surgery, using spectral
domain optical coherence tomography (SD-OCT). METHODS: This is a retrospective,
consecutive, observational case series study. Fifty-two eyes of 52 patients with
primary MH were evaluated. A quantitative analysis of ELM, EZ and IZ defects was
performed preoperatively and at 3 and 6 months postoperatively using SD-OCT. The
correlation between pre- and postoperative ELM, EZ and IZ defects and the best
corrected visual acuity (BCVA) was investigated. RESULTS: The lengths of ELM, EZ
and IZ defects correlated significantly with BCVA in each study period (P <
0.001). Preoperative measures of these band defects were also associated with
visual outcomes 3 and 6 months after surgery (P < 0.05). Considering all
preoperative parameters, the length of the ELM defect was the factor most
strongly correlated with BCVA at 6 months (beta = 0.643, P < 0.012). The
integrity of the ELM was the only factor significantly associated with BCVA at 6
months (beta = 0.427; P = 0.004). CONCLUSIONS: The preoperative length of the ELM
defect is the strongest predictor of visual acuity after MH surgery.
Postoperative integrity of the ELM is significantly associated with visual
restoration after surgical treatment of MH.
PMID- 28412774
TI - Treating the Patient, Not the Disease: Fred Schiffman on Humanism in Medicine.
PMID- 28412773
TI - Massive subretinal and subretinal pigment epithelial hemorrhage displacement with
perfluorocarbon liquid using a two-step vitrectomy technique.
AB - PURPOSE: The purpose of this study was to evaluate the efficacy and visual
outcome of massive submacular hemorrhage (SMH) displacement with a planned two
step pars plana vitrectomy (PPV) using tissue plasminogen activator (tPA) and
perfluorocarbon liquid (PFCL) tamponade. METHODS: A retrospective case series of
patients with age related macular degeneration and SMH was used. All patients
underwent a 23G PPV, subretinal tPA injection and a medium term PFCL tamponade. A
second stage PPV for PFCL removal was performed 7-17 days later. The main outcome
was the change in macular and sub-RPE thickness after 6 months. Secondary
outcomes were visual acuity and complications. RESULTS: Seven patients (seven
eyes) with mean age of 79.85 years were enrolled. The average SMH size was 17.5
disc area (range 4.5-33) with mean symptoms of a duration of 9.5 days (range: 2
21). SMH was successfully displaced in six eyes. Mean macular and sub-RPE
thickness decreased from 1505MU to 711.3MU and 900 MU to 457MU, respectively.
Visual acuity (VA) remained stable in five eyes. Complications included corneal
edema and transient intraocular pressure elevation in three patients.
CONCLUSIONS: SMH displacement using subretinal tPA injection and medium term PFCL
tamponade is an effective alternative treatment option. In our experience, it can
be safely performed, avoiding complications commonly attributed to other
techniques.
PMID- 28412775
TI - Defining Value in Radiation Oncology: Approaches to Weighing Benefits vs Costs.
AB - The passage of the Affordable Care Act in 2010 initiated discussion regarding
transitioning from a fee-for-service arrangement of care reimbursement to value
based care. Cost-effectiveness analysis (CEA) has been used in the past to
quantify value as it relates to the provision of healthcare. New treatments or
techniques being compared with other new or existing therapies or approaches to
care were determined to be cost-effective if the incremental cost-effectiveness
ratio was less than $50,000/life-year or quality-adjusted life-year. This result
was accepted as a proxy for value in care delivery. The calculation of value,
however, is the inverse of CEA, with units measured in outcome/cost. Given the
wealth of medical information now available online, patients are becoming more
sophisticated consumers of healthcare, investigating not only outcomes but also
costs of care associated with different treatment approaches. Costs to be
considered include direct medical costs; the indirect medical costs associated
with treatment; and productivity costs resulting, for example, from time lost
from work when patients must travel to a cancer center or clinic to receive
treatment. Radiation oncologists must be mindful of these costs when designing
treatment plans. Increased adoption of hypofractionated radiation treatment
strategies (ie, higher radiation doses given over a shorter course of treatment)
could increase patient value by reducing direct and indirect medical costs, as
well as productivity costs.
PMID- 28412776
TI - Defining the Value Research Agenda in Radiation Oncology.
PMID- 28412777
TI - How to Address Sexual Problems in Female Cancer Patients.
AB - Sexual health is an important aspect of human life, and cancer does not (and
should not) change that. Data suggest that issues related to sexual function are
quite common among women treated for cancer. However, clinicians often spend
little to no time on the topic. This article provides a concise summary on the
importance of sexual health among women treated for cancer, as well as an
approach that general cancer clinicians can adopt in order to normalize sexual
health issues for their patients. Finally, we provide an overview of sexual
health therapeutics available in the United States and in Europe.
PMID- 28412778
TI - PARP Inhibitors: The Cornerstone of DNA Repair-Targeted Therapies.
AB - The activity and therapeutic licensing of poly(ADP-ribose) polymerase (PARP)
inhibitors is the culmination of 50 years of research. However, the biology,
mechanisms of action, adequate treatment combinations, and targeted populations
for these agents need to be explored further. PARP activity is essential for the
repair of single-strand DNA breaks via the base excision repair pathway. This
pathway is the default repair pathway in cells with deficient high-fidelity
double-strand break homologous recombination (HR) repair, such as occurs with
loss of BRCA1 or BRCA2 function. Therefore, inhibition of PARP function results
in cell death in HR-deficient tumors, and sensitizes tumor cells to cytotoxic
agents that induce DNA damage. Applications of PARP inhibition are now being
expanded beyond tumors with HR deficiency-to HR-competent tumors in which HR has
been synthetically impaired through use of other agents given in combination with
PARP inhibitors, or resulting from PARP inhibition in the setting of BRCA1 or
BRCA2 loss.
PMID- 28412779
TI - Synchronous Bilateral Breast Cancer With Discordant Histology.
PMID- 28412780
TI - How Can We Effectively Address the Medical and Psychological Concerns of
Survivors of Pelvic Malignancies?
AB - Sexual and urinary morbidities resulting from treatment of pelvic malignancies
are common. These treatment sequelae are significantly bothersome to patients and
challenging to address. Awareness of these complications is critical in order to
properly counsel patients regarding potential side effects and to facilitate
prompt diagnosis and management. Addressing these issues often necessitates a
coordinated multidisciplinary approach; however, the effort required often
translates into improvement in patient quality of life. Herein we review the
sexual and urinary side effects that may arise during or after treatment of
pelvic malignancies.
PMID- 28412781
TI - Molecular Testing to Optimize and Personalize Decision Making in the Management
of Colorectal Cancer.
AB - Recent improvements in our understanding of the biology of colorectal cancer have
led to the identification of several important prognostic and predictive markers
of disease-associated risk and treatment response for the individual patient.
Proper utilization of these biomarkers can enable physicians to tailor
therapeutic strategies to maximize the likelihood of response and minimize
treatment toxicity. In the management of colorectal cancer, tremendous progress
has been made in the development of strategies for immune checkpoint inhibition;
in refinement of agents and approaches used in targeted therapy; and in
techniques for molecular subtyping of tumor samples that have identified patient
subgroups with clinically relevant cellular differences potentially affecting
clinical management and treatment outcome. In this article, we discuss several of
the commonly tested markers in colorectal cancer-including microsatellite
instability, RAS/RAF, DPD, HER2, UTG1A1, TS, and Immunoscore-and highlight their
prevalence, prognostic and predictive value, and current role in the overall
treatment paradigm.
PMID- 28412782
TI - [Digital medical techniques play an important role in the development of oral and
maxillofacial surgery].
PMID- 28412783
TI - [Paying attention to the protection of the function organ of submandibular
gland].
AB - Submandibular gland is an important human function organ. With the wide
application of sialoendoscope and new understanding of IgG4 related sialadenitis,
a lot of submandibular glands which were previously considered to be removed are
preserved. However, some submandibular glands which might be preserved are still
unfortunately sacrificed. Therefore, we advocate the popularization and promotion
of new knowledge and techniques and should pay more attention to the protection
of the function organ of submandibular gland.
PMID- 28412784
TI - [Three-dimensional printing and oral medicine].
AB - After 30 years of development, three-dimensional printing technology has made
great progress, and the model and surgical guide have been clinically applied.
The three-dimensional printing of titanium and other metal prosthesis and dental
crown after adequate research will be applied clinically, and three-dimensional
bioprinting and related biological materials need further study. Three
dimensional printing provides opportunities for the development of oral medicine,
which will change the way of clinical work, teaching and research. The dentists
should integrate multi-disciplinary knowledge and understand the essence of new
technology to meet the challenges of the era of digital medicine.
PMID- 28412785
TI - [Functional repair of cleft lip: from anatomical resetting to biomechanical
simulation].
AB - We are no longer entangled in the anatomical resetting of the labial-nasal muscle
itself, but the sight to the muscle fiber level, to study the relationship
between the muscle fiber force line and the labial-nasal shape. In the past ten
years, we focused on the lip of nasal muscle fiber anatomy, imageology and
biomechanics, carried out a series of research works, realized the three
dimensional (3D) visualization of small labial-nasal muscle fiber, established
configuration models of normal and cleft lip with nasal muscle fibers, and put
forward the hypothesis of naso-labial muscle tension band. According to the
biomechanical parameters of lip nasal muscle, cartilage, skin and subcutaneous
tissue, we initially established a biomechanical model elaborating the
relationship between labial-nasal muscle tension lines and surface morphology; we
summed up three muscle tension group which determines labial-nasal contour,
explained the biomechanical mechanism in cleft lip and various lip nasal
deformities, and realized the possibility to freely change the 3D labial-nasal
contour by lip nasal lip nasal muscle tension theory; Finally we carried out
clinical validation in clinical treatment of cleft lip, achieved the effect of
detail cleft lip repairing.
PMID- 28412786
TI - [Oral and maxillofacial surgery residency training in the United States: what can
we learn].
AB - China is currently in the process of establishing formal residency training
programs in oral and maxillofacial surgery and other medical and dental
specialties. Regulatory agencies, and educational and academic institutions in
China are exploring mechanisms, goals and standards of residency training that
meet the needs of the Chinese healthcare system. This article provides an
introduction of residency training in oral and maxillofacial surgery in the
United States, with emphasis on the accreditation standard by the Commission on
Dental Accreditation. As there are fundamental differences in the medical and
dental education systems between China and United States, the training standards
in the United States may not be entirely applicable in China. A competency-based
training model that focus on overall competencies in medical knowledge, clinical
skills and values at the time of graduation should be taken into consideration in
a Chinese residency training program in oral and maxillofacial surgery.
PMID- 28412787
TI - [Progress in studies on the genetic risk factors for nonsyndromic cleft lip or
palate in China].
AB - Cleft lip and palate is the most common congenital defects of oral and
maxillofacial region in human beings. The etiology of this malformation is
complex, with both genetic and environmental causal factors are involved. To
provide a better understanding in the genetic etiology of cleft lip or palate,
the author summarized recent years studies based on Chinese population. Those
researches included validation of some candidate genes for cleft lip or palate,
using genome wide association analysis which included six independent cohorts
from China to elucidate the genetic architecture of non-syndromic cleft lip with
or without cleft palate in Chinese population and finally found a new
susceptibility locus. This locus was on the 16p13.3 (rs8049367) between CREBBP
and ADCY9. It has been mentioned common methods of genetic analysis involved in
the researches on cleft lip or palate in this paper. Furthermore, we try to
discuss new methods to illustrate the etiology of cleft lip and palate that could
provide more inspiration on future researches.
PMID- 28412788
TI - [Guidelines for the use of sialendoscopy in salivary gland diseases].
AB - Salivary gland disease is a common disease in oral clinical care. Sialendoscopy
technique has been widely used in salivary gland disease in recent years.
Compared with traditional treatment, it is a safe, minimally-invasive and cost
effective technique, thus presenting significant benefits both for the patient
and the health-care system. As for providing a comprehensive and updated source
of current information on sialendoscopy, it's important to standardize the
operating processes for salivary gland sialendoscopy. Experts from Chinese
Stomatological Association have made a guideline about diagnosis and treatment of
salivary gland disease by sialendoscopy, based on domesticpractical experience
and international reports.
PMID- 28412789
TI - [Development and preliminary clinical application of home-made temporomandibular
joint prostheses].
AB - Objective: To explore the clinical application of home-made temporomandibular
joint (TMJ) prostheses. Methods: Self-developed TMJ prostheses were applied for
end stage osteoarthritis, TMJ ankylosis, condylar tumors after biomechanical
examination. The stability of the prostheses toward bone was evaluated during
operation. Post-operative CT scans and clinical follow-ups were taken to check
changes of mouth opening, position of the prostheses, bone resorption around the
screws, and heterotopic bone formation around artificial condyle. Results: There
were 6 patients accepted 7 prostheses smoothly without infection and other
complications. Post-operative follow-ups were from 6 to 13 months with a mean of
7.6 months. Mouth opening was significantly improved from (16.2+/-14.4) mm before
operation to (31.5+/-4.8) mm during follow-ups (P=0.01). All prostheses were
stable without screw loose and heterotopic bone formation. Conclusions: Home-made
TMJ prostheses were stable after primary clinical application, but the long-term
results need to be observed.
PMID- 28412790
TI - [A preliminary study of three-dimensional bio-printing by polycaprolactone and
periodontal ligament stem cells].
AB - Objective: To investigate the technical scheme of three-dimensional (3D) bio
printing by polycaprolactone (PCL) and periodontal ligament stem cells (PDLSC).
Methods: To manufacture a 3D bio-printing body, PDLSC were used as seed cells,
and polycaprolactone (PCL) was used as the 3D printing scaffold material. Print
size was designed at 13.0 mm*13.0 mm, and mesh size was 0.25 mm*0.25 mm (group A)
and 0.75 mm*0.75 mm (group B). Cell counting kit-8 was used to detect the
proliferation of PDLSC on day 1, day 3 and day 5 respectively. The state of the
cells in the 3D printing structure was observed by scanning electron microscope
(SEM). Osteoblastic ability of the 3D printing mixture was observed after 14 days
of culture by alizarin red mineralized nodule staining method. Results: Using
PDLSC as seed cells and PCL as a scaffold to print two mesh-sized 3D bodies. The
body thickness and porosity of group A and group B were 1.1 mm, 1.5 mm and 49.3%,
72.5% respectively. SEM showed that PDLSC proliferated significantly on two sets
of 3D structure which was more obvious in group A. In vitro osteogenic induction,
a large number of red mineralized nodules formed on the 3D structure.
Conclusions: A 3D structure with a self-defined shape and size was successfully
printed using 3D bio-printing equipment. PDLSC can grow and proliferate on the
structure.
PMID- 28412791
TI - [Surface roughness and gloss of novel flowable composites after polishing and
simulated brushing wear].
AB - Objective: To investigate surface properties of novel flowable composites after
polishing and simulated brushing wear, compared to their pasty counterpart.
Methods: Composites employed in this study were: three flowable composites (A1:
Clearfil Majesty ES Flow; B1: Beautifil Flow Plus F00; C1: Filtek Bulk Fill) and
three paste composites (A2: Clearfil Majesty; B2: Beautifil; C2: Filtek Z350.
Eleven disk-shaped specimens were made for each material. The specimens were
cured, then subjected to sandpaper finishing for 20 s, one-step polishing for 30
s, finally subjected to simulated brushing for 10 000 cycles. Surface roughness
and glossiness were measured before finishing, after finishing, after polishing,
after 5 000 brushing cycles and after 10 000 brushing cycles, respectively. Data
obtained were analyzed using two-way ANOVA method. Scanning electron microscope
was employed to examine the microscopic appearance of each material. Results:
Surface roughness (0.11~0.22 MUm) and glossiness (74.25~86.48 GU) of each
material were similar after one-step polishing. After brushing simulation,
roughness increased significantly and glossiness decreased significantly for each
material (P<0.05). Group A1 presented the best gloss ([50.68+/-1.58] GU) after
final wear (P<0.05). Flowable composites of group A1 and B1 tested in the present
setup showed better surface properties compared to their pasty counterpart (group
A2 and B2). Conclusions: Within the limit of this study, flowable composites
tested in the present research can obtain similar surface polish or even better
than the paste composite counterpart.
PMID- 28412792
TI - [Isolation of cariogenic Streptococcus mutans and the inhibitory effect of egg
yolk antibody on caries].
AB - Objective: To isolate the cariogenic Streptococcus mutans (Sm) strains and study
the therapeutical effect of egg yolk antibody (IgY) of the Sm on dental caries
development. Methods: Sm strains were isolated from the children's dental plaque
samples. Morphological, biochemical and molecular biological methods were applied
to identify the serotype, acid producing and adhesion abilities of isolated Sm
strains. After inactivation one of the Sm strains was used as antigen to immune
laying hens to collect and extract the specific anti-Sm IgY. The rats were
infected with Sm (serotype e). After 16 weeks of infection, all the rats were
found developing dental caries. The rats were then randomly divided into two
groups. The rats in experimental group were supplied with diet containing anti-Sm
IgY while the rats in control group with normal IgY. All rats were sacrificed
after another 8 weeks' observation. The degree of caries for each rat was
assessed using Keyes' method. Results: We isolated 7 Sm strains from the
children's dental plaque samples in the present study. The numbers of serotype c,
e, f, k were 3, 2, 0 and 2, respectively. All strains showed similar
morphological and biochemical characters as standard UA159 Sm strain, and
possessed strong capabilities of acid production and adherence. Interestingly,
even the same serotypec strains, such as No.3 and No.7 strains, demonstrated
significant difference on acid producing and adherence capabilities. After 16
weeks infection with serotype e strain, the rats' mandibular teeth were
apparently decayed, and treatment with specific anti-Sm IgY obviously attenuated
the development of caries in the experiment group rats (16.4+/-2.0) compared with
that in the control group rats (30.2+/-9.3) (P<0.05) determined by Keyes' method.
Conclusions: Seven cariogenic Sm strains of different serotypes were isolated,
which possesses similar morphology and biochemical characters. Although belonging
to the same serotype strains they always show significant difference in acid
producing and adherencec apabilities. Further experiment provides evidences that
the serotype e strain could obviously induce caries independently, and employment
of specific anti-Sm IgY as passive immunotherapy additive might effectively
inhibit the further development of dental caries.
PMID- 28412793
TI - [The effect of restraint stress on masseter mechanical hyperalgesia and the
activity of neurons and astrocytes in the spinal trigeminal nucleus caudalis in
rats].
AB - Objective: To investigate the effect of restraint stress on masseter mechanical
hyperalgesia and the activity of neurons and astrocytes in the spinal trigeminal
nucleus caudalis (Vc). Methods: The animals were randomly divided into the
control group, 1-, 3-, 5-, 7-, 9-, 11-and 14-day stress groups, with 10 rats in
each group. The body weight increase and behavior tests were used to testify the
animal model. The mechanical sensitivity of masseter of the rat before and after
the stress was measured with Von Frey filaments. Histological examinations were
used to evaluate the expression of neuronal c-fos and astrocytic glial fibrillary
acidic protein (GFAP). Results: Restraint stress resulted in remarkable
mechanical allodynia in the masseter muscle. The head withdrawal threshold was
significantly lower in the 7-, 9-, 11-and 14-day stress groups ([0.071+/-0.011],
[0.059+/-0.020], [0.052+/-0.011], [0.033+/-0.011] N) than that in the control
group ([0.120+/-0.025] N) (P<0.05). Compared to the control group, the rats in
the 1-day stress group showed a significant increase of c-fos in neurons of the
Vc and then declined to normal level after 1 week gradually. The GFAP expression
in astrocytes of the Vc was significantly increased in the 7-, 9-, 11-and 14-day
stress groups (4.3+/-1.0, 4.5+/-0.6, 4.6+/-0.5, 4.8+/-1.3) compared with the
control group (2.0+/-0.8) (P<0.05). Conclusions: Chronic restraint stress could
lower the threshold of mechanical allodynia in the masseter muscle and activate
the neurons and astrocytes in Vc. The activation of neurons and astrocytes plays
an important role in the masseter hyperalgesia induced by restraint stress in
rats.
PMID- 28412795
TI - [Pay attention to the complexity of cataract surgery of no vitreous eyes].
AB - With wide-spread performance of pars plana vitrectomy, cataract surgeries with no
vitreous are getting more and more. This kind of surgery has great difference
between individuals and it lacks randomized large sample clinical trial. Surgical
strategy decision was basically relied on the surgeon's personal experience. We
should fully aware the individual and common characteristics of no vitreous
cataract surgery. Surgical time should be carefully decided. Complete ocular
examination, evaluation, design of cataract surgical procedure and appropriate
intra-ocular lens selection are needed. We must pay highly attention on the
cataract surgery of no vitreous eyes. (Chin J Ophthalmol, 2017, 53: 241-243).
PMID- 28412794
TI - [Effects of alginate/collagen scaffold on cell proliferation and differentiation
of human adipose-derived mesenchymal stem cells].
AB - Objective: To build scaffold materials with different concentrations of alginate
and collagen, and to observe the effects of alginate/collagen ratio on the
proliferation of human adipose-derived mesenchymal stem cells (hAMSC) and
osteogenic differentiation. The optimal concentration of alginate/collagen will
be chosen for constructing hydrogel that will be used for bone tissue
engineering. Methods: Soluble hydrogel scaffold materials containing
alginate/collagen were prepared, and the following groups were established based
on different alginate/collagen ratio: 4?1 (group A), 2?1 (group B), and 1?1
(group C). Cell proliferation on the material surface was observed using the cell
counting kit-8 (CCK-8) assay, while cell viability in each material group were
observed using live/dead staining. Quantitative real-time PCR(qPCR) was used to
measure the differential expression of osteogenesis-related genes on and in the
materials. Immunofluorescence staining was used to measure the differential gene
expression of osteogenesis-related proteins in each group. Results: The results
from the CCK-8 assay showed increasing cell proliferation rate on the lyophilized
hydrogel material surface as the collagen concentration increased, and the
highest cell proliferation was observed in group C. Live/dead staining assay
indicated that cells were able to proliferate in all three types of hydrogel
materials, and the highest cell viability was found in material from group B
([87.50+/-2.65]%). qPCR showed that the expression of osteogenesis-related genes
in group C was the highest, among the three groups, while the expression of
osteocalcin in group B was significantly higher than those in the other two
groups (P<0.05). Immunofluorescence staining was carried out for osteocalcin on
and in the hydrogel material and the results were consistent with that of qPCR.
Conclusions: The alginate/collagen scaffold materials did not show adverse
effects on the cell proliferation of hAMSC and osteogenenic differentiation. Bone
tissue engineering can use 10% hydrogel material, and when the sodium alginate
and collagen have a ratio of 2?1, the hydrogel can be conducive to cell
differentiation and proliferation.
PMID- 28412796
TI - [Multiple issues in multifocal intraocular lens].
AB - The occurrence of multifocal intraocular lens (MIOL) is known as an important
period in the development of cataract surgery, which can provide a simultaneous
vision without the use of spectacles or contact lenses. However, in the current
stage, MIOL implantation may also lead to decreased visual acuity and increased
risk of photic phenomena, thus in some instance a second procedure to exchange
the MIOL is necessary. Optimizing visual outcomes of MIOL implantation and
controlling adverse effects has become the focus for ophthalmologists. In the
future, a more remarkable, flexible and high cost-effective intraocular lens
(IOL), which can mimic human natural crystalline lens, should emerge. (Chin J
Ophthalmol, 2017, 53: 244-248).
PMID- 28412797
TI - [Correlation between axial length and corneal curvature and spherical
aberration].
AB - Objective: To discuss the correlation between axial length and corneal curvature
and corneal spherical aberration in a group of cataract patients with axial
length greater than 24 mm. Methods: Retrospective case series. This study
comprised 117 (234 eyes) age-related cataract patients. There were 51 men
(43.59%) and 66 women (56.41%) with mean age of (69.0+/-8.7) years (range from
52.0 to 85.0 years). The average axial length was 27.6+/-1.8 (range from 24.2 to
31.9 mm). We devided them into four groups according to the axial length. A-scan
was used to measure the axial length and Pentacam was used to get the corneal
curvature and corneal spherical aberration of both anterior and posterior
surface. kolmogorov-smirnov test was used to check the normal distribution. ANOVA
test was used to compare eachcorneal parameter among different groups. Pearson
correlation analysis was used to obtain the correlation of corneal parameters in
groups. Results: There were correlations between the axial length and the
anterior and posterior corneal curvature (r=-0.213, r=0.174, respectively,
P<0.05). No correlation was found between the axial length and anterior or
posterior corneal spherical aberration (r=-0.114, 0.055, respectively, P>0.05).
Mean values of corneal anterior surface curvature were (45.26+/-1.60) D (group
1), (44.17+/-1.45) D (group 2), (44.40+/-1.99)D (group 3), and (44.53+/-1.69) D
(group 4) respectively. Mean values of corneal posterior surface curvature were(
6.57+/-0.26)D (group 1), (-6.40+/-0.24)D (group 2), (-6.41+/-0.38)D (group 3),
and (-6.43+/-0.26)D (group 4) respectively. There were significant difference of
corneal anterior and posterior surface curvature among 4 groups (P=0.004,
P=0.001). There was significant difference of corneal curvature of anterior
surface in group 1 compared to group 2 and group 3(P<0.01, P=0.01). There was
significant difference of curvature of posterior surface in group 1 compared to
group 2 and group 3, respectively (P<0.01). Mean values of anterior surface
corneal spherical aberration were (2.09+/-0.53) MUm (group 1), (1.90+/-0.44) MUm
(group 2), (2.00+/-0.74) MUm (group 3), and (1.78+/-0.52) MUm (group 4)
respectively. Mean values of posterior surface corneal spherical aberration were
(2.69+/-1.15) MUm (group 1), (2.46+/-1.16) MUm (group 2), (2.92+/-2.51) MUm
(group 3), and (2.69+/-1.13) MUm (group 4) respectively. No correlation was found
in anterior and posterior surface corneal spherical aberration(P>0.05) among
different groups. Conclusions: The eye with a longer axial length have a flatter
cornea. Cornea fails to compensate for axial length elongation when the axial
length is longer than 28mm. The corneal spherical aberration varies among
individuals, which suggests us to do the customized measurement before cataract
surgery to make a decision on choosing the aspherical intraocular lens. (Chin J
Ophthalmol, 2017, 53: 255-259).
PMID- 28412799
TI - [Long-term outcomes after cataract surgery in infants with congenital cataract].
AB - Objective: To observe the long-term outcomes after congenital cataract surgery
performed prior to 36 months of age. Methods: A retrospective case study was
conducted. Thirty-two cases (57 eyes) of congenital cataract were included from
January 2004 to January 2012. All patients received intraocular lens (IOL)
implantation with posterior continuous curvilinear capsulorhexies and anterior
vitrectomy after cataract extraction and were followed up. At the last visit, the
best corrected visual acuity (BCVA) was determined and postoperative
complications were evaluated during follow-up with a longest time of 13 years.
Non-normal distribution showed in median M (minimum and maximum). Data were
analyzed by Kruskal Wallis single factor variance analysis and multiple
comparison. The independent Mann-Witney U test was used to analyze non-normal
distribution data. Results: There were thirty-two cases (57 eyes) of congenital
cataract including 7 unilateral cases and 25 bilateral cases. The median age at
cataract extraction was 6.0months; the median IOL implantation age was 28.0
months and the median duration of follow-up after cataract extraction was 67.0
months. The median postoperative BCVA was (LogMAR) 0.52. Unilateral and bilateral
cataract postoperative BCVA difference had no statistical significance (U=107,
P>0.05). Patients received cataract surgery in 2 to 4 months, the postoperative
BCVA was better than in 5 to 8 months. The difference was statistical
significance (H=-15.33, P<0.05). BCVA after IOL implantation before 24 months
were significantly better than after 30 months. The difference had statistical
significance(H=-20.61,-20.78, P<0.05). Postoperative complications were posterior
capsular opacity (5 eyes; 8.77%), glaucoma (2 eyes; 3.51%), strabismus (17 eyes;
29.82%) and nystagmus (30 eyes; 52.63%). Conclusions: Most infantile cataract
surgeries performed prior to 36 mouths of life together with the implantation of
IOL can achieve good visual acuity. No serious complications occurred. (Chin J
Ophthalmol, 2017, 53: 266-273).
PMID- 28412798
TI - [Intraocular lens power calculation for high myopic eyes with cataract:
comparison of three formulas].
AB - Objective: To compare the accuracy of three different formulas for intraocular
lens power calculation in high myopic eyes with cataract and analyze their
influencial factors. Methods: One hundred and three high myopic patients of
cataract (103 eyes), with average age of 60.2+/-8.8 years old (39.0-77.0),
including 45 male and 54 female and with axial length >= 26 mm were enrolled in
this retrospective case-series study. All of them underwent routine ocular
examination and IOLMastermeasurement preoperatively and then underwent
phacoemulsification through temporal clear-corneal incision with implantation of
HumanOptic posterior chamber Intraocular lens (IOL). All analyses were conducted
using SPSS version 19.0. Repeated-measures analysis of variance was applied to
compare the refractive results one month postoperatively with the predicted IOL
powers calculated by SRK/T, Holladay 1, or Haigis formula before surgery. The
differences were further compared based on different grouping of axial length
(AXL), corneal curvature (K) and corneal astigmatism (CA). The accuracies of the
three formulas were analyzed using Bland-Altman analyses and the possible error
sources of each formula were analyzed using multiple regression model. Results:
The majority of patients enrolled had hyperopic shift after cataract surgery. The
mean errors (ME) of the three formulas were SRK/T: 0.70+/-0.89D, Holladay 1:
(1.20+/-0.88) D and Haigis: (0.60+/-0.88) D; the mean absolute errors (MAE) of
the three formulas were (0.81+/-0.79) D, (1.23+/-0.84) D and (0.76+/-0.74) D,
respectively. Both ME and MAE of Holladay formula were significantly greater than
the other two formulas (F=86.31, P<0.01). Besides, the proportion of patients
having a prediction error within 0.50 D was lower in those using Holladay formula
(20.4%, 21/103) than the other two (SRK/T: 38.8%, 40/103, chi(2)=8.41, P<0.01,
Haigis: 45.6%, 47/103, chi(2)=14.84, P<0.01). Bland-Altman analyses showed that
the accuracies of all the three formulas were acceptable in patients of cataract
with high myopia in clinical practice. ME and MAE tended to be larger with longer
axial length, larger corneal curvature and astigmatism of the patients in all
three formulas. However, in eyes with axial length> 30 mm or corneal curvature
<=43.00 D, the MAE of Haigis formula was lower than that of SRK/T formula
(F=63.26,63.94, both P<0.01). The prediction error of SRK/T formula was
positively correlated with axial length and corneal astigmatism (F=33.97, r=0.66,
beta=0.48, P<0.01 and beta=0.42, P<0.01), while for Holladay and Haigis formulas,
in addition to the previous two factors, the errors were also positively
correlated with mean corneal curvature (Holladay 1: F=31.26, r=0.72, AXL:
beta=0.52, P<0.01, K: beta=0.20, P<0.05 and CA: beta=0.37, P<0.01; Haigis:
F=30.96, r=0.72, AXL: beta=0.33, P<0.01, K: beta=0.40, P<0.01 and CA: beta=0.37,
P<0.01). Conclusions: In the selection of IOL formula for high myopic patients
with cataract, Haigis or SRK/T would reduce the prediction error and serve as the
more accurate formulas than Holladay 1. Haigis formula may be more accurate than
SRK/T formula in case of AXL>30 mm or K<=43.00 D. (Chin J Ophthalmol, 2017, 53:
260-265).
PMID- 28412800
TI - [Visual quality comparison after multifocal toric intraocular lens or monofocal
toric intraocular lens implantation].
AB - Objective: To compare visual quality and satisfaction after multifocal toric
intraocular lens (Acrysof IQ Restor toric, ART) and monofocal toric intraocular
lens implantation in patients. Methods: It was a prospective nonrandomized Phase
III clinical trial. Patients with age-related cataract and corneal astigmatism
were enrolled and accepted phacoemulsification combined with implantation of
intraocular lens (IOL) in Henan Provincial Eye Hospital during March 2013 to
December 2014. Fifty-six cases were divided into two groups according to which
IOL they chose. ART group included 28 cases (3l eyes) aged from 41.0 to 72.0
years, with an average age of 61.5 years; toric group included 28 cases (33 eyes)
aged from 42.0 to 75.0 years, with an average age of 63.5 years. Three months
postoperatively, uncorrected distance visual acuity (UDVA) at 5, 70, 40 cm,
corrected distance, intermediate, and near visual acuities, defocus curve,
residual refractive astigmatism, rotational stability of the IOL, contrast
sensitivity and patientsatisfaction were evaluated. All data were processed by
statistic package deal SPSS 16.0. Postoperative visual acuity, residual
astigmatism, IOL axial rotation and contrast sensitivity were compared by
independent samples t test; preoperative and postoperative corneal astigmatism
were compared by paired t-test; spectacle independency and halo incidence were
processed by chi(2) test; visual satisfaction score was analyzed by Mann-Whitney
test. Results: At 3 months postoperatively, in ART group, UDVA was (0.04+/-0.05),
UIVA was (0.24+/-0.15), UNVA was (0.20+/-0.24). While in Toric group, UDVA was
(0.06+/-0.04), UIVA was (0.30+/-0.13), UNVA was (0.47+/-0.21). There was no
significant difference in UDVA between two groups(t=0.79, P=0.433). But in ART
group, UIVA and UNVA were markedly better than those in Toric group(t=2.74,
P=0.008; t=3.45, P<0.01). Depth of focus was 5.50 D (+2.00--3.50 D) in the ART
group and 2.50 D (+1.00--1.50 D) in the Toric group. Average postoperative
residual astigmatism was (-0.45+/-0.41)D in ART group and (-0.41+/-0.32)D in the
Toric group. There was no significant difference between two groups (t=1.05,
P=0.304). Average IOL rotation test was (2.95 degrees +/-1.34 degrees ) in the
ART group and (2.75 degrees +/-1.64 degrees ) in the Toric group. There was no
significant difference between two groups (t=0.67, P=0.452). Spectacle
independency was achieved by 85.7% of patients in the ART group and 32.1% in the
Toric group. There was no signifcant difference in distant visual satisfaction
scores between the two groups(Z=0.71, P>0.05), while the intermediate and near
visual satisfaction scores were significantly different(Z=2.27, P<0.05; Z=2.60,
P<0.05) Conclusions: Both of the ART IOL and toric IOL can correct patients
astigmatism. Implantation of ART IOL in patients with cataract and corneal
astigmatism provided excellent distance, intermediate, and near visual outcomes.
It provided better predictability of the refractive results, nice rotational
stability, and good optical performance. At the same time, it improved the
spectacle independency of cataract patients with astigmatism. (Chin J Ophthalmol,
2017, 53: 274-280).
PMID- 28412801
TI - [Preliminary report on the application of femtosecond laser-assisted anterior
capsulotomy in intumescent white cataract surgery].
AB - Objective: To assess the effect of femtosecond laser-assisted anterior
capsulotomy in intumescent white cataract surgery. Methods: Retrospective case
series study. One hundred and fifty cataract patients (150 eyes) from June 2014
to June 2015 in Wuhan Aier ophthalmology hospital were enrolled in this study.
They were divided into three groups: 50 intumescent white cataract patients (50
eyes) in the study group were performed femtosecond laser-assisted capsulotomy
(LenSx system) operation selectively. Fifty intumescent white cataract patients
(50 eyes) underwent normal manual continuous circular capsulorhexis as the
control group 1. Fifty other types cataract patients (50 eyes) underwent
femtosecond laser-assisted capsulotomy as the control group 2. To observe the
complications such as radial tear in anterior capsule, posterior capsule rupture
and vitreous prolapse occurred during operations in each group respectively. The
microscopic images of the free anterior capsule after dyeing were observed in the
studygroup and the control group 2. Using the German company Oculus Pentacam
three-dimensional anterior eye segment system to collect the Scheimplug images of
each group at 1, 3, 6 months and 1 year after operation. The data were analyzed
by SPSS19.0 software package. Complications during operations in all groups were
compared with Fisher exact test. The eccentricity and tilt of IOL in each group
were analyzed by single factor analysis of variance. The SNK-q test was used to
compare the different follow-up time groups. Results: One hundred and fifty
patients aged from 50 to 86 years old, including 72 male cases and 78 female
cases. In study group, radial tear in anterior capsule occurred in 2 eyes (4%),
adherent tongue-like capsule adhesion was found in 6 eyes (12%), incomplete
capsulotomy button happened in 2 eyes (4%), and posterior capsule rupture and
vitreous prolapse occurred in 1 eye (2%). In the control group 1, radial tear in
anterior capsule occurred in 8 eyes (16%) and posterior capsule rupture and
vitreous prolapse occurred in 3 eyes (6%). The cases number of radial tear in
anterior capsule and posterior capsule rupture and vitreous prolapse in the study
group was obviously lower than the control group 1. The difference was
statistically significant (P<0.05). In the control group 2, all 50 eyes were
successfully completed. The implantation was uneventful and the IOL was centered.
And posterior capsular rupture and vitreous prolapse did not occur. The
difference was statistically significant between the study group and the control
group 2 (P<0.05). After 1 year follow-up, the study group and the control group 2
showed no significant IOL tilt and eccentricity. The eccentricity and tilt of IOL
in horizontal and vertical direction in control group 1 were significantly higher
than those in the study group (F was 2.31, 1.10, 2.78 and 2.90 respectively) and
control group 2 (F was 2.50, 2.32, 2.56 and 2.18respectively). The difference was
statistically significant (P<0.05). Conclusions: Femtosecond laser-assisted
anterior capsulotomy is accurate circle and center to avoid IOL eccentricity and
tilt caused by capsular bag contraction asymmetrically after implantation, so as
to ensure the long-term stability of the visual quality postoperatively. (Chin J
Ophthalmol, 2017, 53: 281-287).
PMID- 28412802
TI - [Analysis of the effect of different surgical methods on the cavernous hemangioma
of the deep orbit].
AB - Objective: To explore the effect of the surgical removal of orbital deep
cavernous hemangioma following the concept of minimal surgical invasion. Methods:
Retrospective case series study. Sixty-three cases with surgical removal of deep
orbital cavernous hemangioma were collected in the Affiliated Eye Hospital of
Nanchang University from May 2012 to August 2015. There were 29 males and 34
females. The age was from 17 to 69 years with mean age (45+/-11) years.The
surgical methods the conjunctival approach orbital surgery, lateral orbital
surgery, medial skin orbital surgery, lateral orbital conjunctiva conjunctival
pathway and endoscopic nasal approach were chosen for different cases. The visual
acuity, visual field and electrophysiological examination were analyzed before
and after operation. Result: Sixty-three patients underwent complete surgically
removal of the tumor. Among them, 32 cases were conducted by conjunctival
approach, 24 cases had improved visual acuity, 5 cases had no change of visual
acuity, 3 cases had decreased visual acuity. Seventeen cases performed with
lateral open orbital surgery had improved visual acuity in 11 cases, no change in
visual acuity in 3 cases and decreased visual acuity in 3 cases postoperatively.
Six cases with approach of the medial orbital surgery had improved visual acuity
in 4 cases, no change of visual acuity in 1 case and decreased visual acuity in 1
case postoperatively. Six cases with approach of outside open orbital surgery
combined with medial conjunctival pathway had improved visual acuity in 4 cases,
no change of visual acuity in 1 case and decreased visual acuity in 1 case
postoperatively. Two cases performed with endoscopic nasal approach. One of them
had normal visual function and no change after surgery. Another had impaired
visual function pre-operatively and it came back to normal postoperatively.
Conclusions: With the concept of minimal surgical invasion, the choice of
appropriate surgical approach can save patients with the greatest degree of
visual function and even improve the visual function of the patients with orbital
cavernous hemangioma. (Chin J Ophthalmol, 2017, 53: 288-293).
PMID- 28412803
TI - [Association analysis between LOXL1 gene and exfoliation syndrome].
AB - Objective: To evaluate the association of LOXL gene and XFS/XFG in Chinese
population. Methods: Experimental research. Fifty unrelated patients from
shenzhen Eye Hospital and Beijing Tongren Hospital with exfoliation syndrome or
exfoliation glaucoma and 100 control subjects were included. All the seven exons
and the splicing region were amplified by polymerase chain reaction (PCR) and
were directly sequenced. The comparison of allelic frequencies and genotype
frequencies between case and control groups was performed using standard chi(2)
test. Result: Allelic association analysis showed that there were significant
differences in the allelic distributions between the two groups for two loci in
the LOXL gene: int6: 25975 C>A and ex7:26145 G>A. The frequency of A allele at
int6: 25975 C>A was significantly higher in cases than in controls (chi(2)=92.31,
P<0.01), OR=1.66(95%CI:1.42-1.96). The frequency of genotype CA was significantly
higher in cases than in controls (chi(2)=109.09, P<0.01), OR=5.00 (95%CI: 2.87
8.70). The frequency of A allele of ex7: 26145 G>A was significantly higher in
cases than in controls (chi(2)=79.25, P<0.01), OR=1.54 (95%CI: 1.33-1.78). The
frequency of genotype GA was significantly higher in cases than in
controls(chi(2)=91.30, P<0.01), OR=3.33 (95%CI: 2.18-5.09). Haplotype AA and AG
were risk and haplotype CG was protective for the disease. Conclusions: Two loci
in the LOXL1 gene were found to be associated with XFS/XFG. Further study is
needed to unravel the effect of LOXL1 on thedevelopment of the disease.(Chin J
Ophthalmol, 2017, 53: 294-299).
PMID- 28412804
TI - [Status and analysis of off-label drug use in department of ophthalmology].
AB - Objective: To investigate and analyze the status of off-label drug use in
department of ophthalmology of Beijing Tongren Hospital. Methods: Cross-sectional
study. Prescription evaluation, off-label drug use application and temporary
medicine purchase application were collected from January 2013 to March 2015. The
off-label use of medication in department of ophthalmology were filtered out and
analyzed according to the category of medications, the category of the off-label
use of medication and the strength of evidence for the off-label use of
medication. Results: Thirty-seven items of off-label uses of medication were
included in this study. The off-label use of medication focused on the
indications (19 items, 51.4%) and route of administration (18 items, 48.6%) in
this study. Nineteen category of medication were involved, which accounted for
1.3% (19/1 462) drugs in the hospital formulary.The top 2 category of medication
were adrenocorticoid drugs (21.1%, 4/19) and antitumor drugs (21.1%, 4/19). There
are evidence to support 37 items of off-label drug uses. 5 items (13.5%) of off
label drug uses were labeled uses approved by Food and Drug Administration. One
item (2.7%) of off-label drug use was in accord with international guidelines.
Twenty items (54.1%) of off-label drug uses were in accord with expert consensus.
Eight off-labels were evaluated by Micromedex, while the other 78.4% (29 items)
were not evaluated by Micromedex. Conclusions: The off-label use of medications
exists widely in department of ophthalmology, having its necessity and
rationality. But we should pay attention to its standard management. (Chin J
Ophthalmol, 2017, 53: 300-304).
PMID- 28412805
TI - [The observation of tacrolimus eye drops preventing the early immunological
rejection after penetrating keratoplasty for fungal keratitis].
AB - Objective: To observe the early immunological rejection prevention effect of
tacrolimus eye drops combined with glucocorticoids on fungal keratitis patients
who received penetrating keratoplasty (PKP). Methods: In a retrospective case
series study, medical records of fungal keratitis patients who received PKP in
Shandong Eye Institute from March 2013 to December 2015 were reviewed. Twenty-six
patients (26 eyes) were given tacrolimus eye drops, and 24 patients (24 eyes)
were given 1% cyclosporine A eye drops immediately after PKP. Two weeks after
PKP, these patients were given low concentration of glucocorticoids if no fungal
recurrence was found. Immune rejection, fungal recurrence, intraocular pressure,
and drug irritation symptoms were monitored. Data were analyzed by chi-square
test and independent t-test. Results: The average follow-up was 7 months (range,
3 to 12 months) postoperatively. The rejection rate was 15.3% in the tacrolimus
group and 47.8% in the cyclosporine A group (chi(2)=5.510, P<0.05). One patient
in the tacrolimus group and two patients in the cyclosporine A group suffered
fungal recurrence. Two patients in the tacrolimus group and four patients in the
cyclosporine A group had secondary glaucoma. The intraocular pressure was
controlled. Three patients receiving tacrolimus eye drops and 13 patients
receiving cyclosporine A eye drops had mild irritation symptoms. Conclusions:
Tacrolimus eye drops combined with low concentration of glucocorticoids can
prevent the early immunological rejection after PKP for fungalkeratitis
effectively and safely. (Chin J Ophthalmol, 2017, 53:305-310).
PMID- 28412806
TI - [Correlation between Alzheimer disease and cataract].
AB - Alzheimer disease (AD) is a progressive neurodegenerative disease and is a
leading cause of dementia among elders. In the early phase of AD, even if
neuropathological changes presented, but little to none clinical symptoms were
found. Therefore, it is difficult to diagnose AD in the beginning of the disease.
It is vital to find a noninvasive way for both diagnose and prognosis of AD.
Studies have found that beta-amyloid (Abeta) works as a connection between AD and
cataract. This review will discuss AD and its associated markers which may be
present in the lens and cataract related AD to provide more basis for early
diagnosis of AD. (Chin J Ophthalmol, 2017, 53: 314-316).
PMID- 28412807
TI - [Clinical features, risk factors and progresses on treatment of recurrent Vogt
Koyanagi-Harada disease].
AB - Vogt-Koyanagi-Harada disease(VKH) is a bilateral, granulomatous panuveitis
associated with central nervous system, auditory, and integumentary
manifestations. Clinically, VKH usually responds well to early aggressive
glucocorticosteroid treatment and may be cured without any clinically significant
sequelae. Some patients, however, may enter the chronic recurrent phase, which
may result in marked loss of vision due to complications such as complicated
cataract, secondary glaucoma and maculopathy. Recurrent VKH is mainly
characterized by anterior uveitis associated with thickening of the choroid.
Initial poor visual acuity, severe anterior chamber reaction, choroidal
folds,rapid tapering of systemic corticosteroids or inadequate duration of
treatment, and development of extraocular manifestations may be risk factors of
disease recurrence. Prolonged glucocorticosteroid treatment has been suggested as
effective strategy for recurrence of VKH. The positive effects of other
immunosuppressive agents and biologic agents on treatment of chronic recurrent
and refractory VKH have been gradually recognized by the uveitis community. (Chin
J Ophthalmol, 2017, 53: 317-320).
PMID- 28412808
TI - Spontaneously Assembled Nano-aggregates in Clear Green Tea Infusions from
Camellia ptilophylla and Camellia sinensis.
AB - Tea nano-aggregates spontaneously assembled in clear tea infusions are considered
as the precursors of tea cream, although their molecular basis remains obscure.
Here, we characterized nano-aggregates in green tea infusions from Camellia
ptilophylla, a peculiar tea variety with 6.0% of theobromine, and Camellia
sinensis as the control for comparative purpose. Numerous negatively charged
spherical colloidal particles of 50-100 nm in diameter were primarily found in
both green tea infusions. Catechins, proteins, and carbohydrates were confirmed
as the dominant components in green tea nano-aggregates. In addition, iron,
copper, nickel, proteins, and gallated catechins exhibited higher aggregating
affinity than other components, whereas methylxanthines and calcium contributed
to the transformation of nano-aggregates into tea cream. Green tea nano
aggregates were partly destroyed by simulated gastrointestinal digestion, and
removing theses peculiar particles dramatically attenuated the bioaccessibility
of methylxanthines, theanine, and some catechin monomers in green tea infusions.
This study enhanced our knowledge of molecular interactions in the formation of
green tea cream and provided insight into physicochemical profiles, phytochemical
nature, and functional effects of green tea nano-aggregates.
PMID- 28412809
TI - Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid,
a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast
Cells, and Rat Uterine Tissues.
AB - Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit
diverse estrogenic activities. In this study we investigated the estrogenic
activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy
1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound
elicited different transcriptional activities of estrogen agonist at low
concentrations (0.1-1 MUM) and antagonist at high concentrations (10-50 MUM)
using luciferase reporter gene assay in HEK-293T cells. In human breast cancer
(MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating
ERalpha-signaling and suppressing estrogen-responsive genes, whereas it
attenuated the uterotrophic effect of estrogen in immature ovariectomized rats.
Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell
differentiation and the related bone markers, indicating its positive osteogenic
effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist
of catechol diarylheptanoid from C. comosa, which is scientific evidence
supporting its potential as a dietary supplement to prevent bone loss with low
risk of breast and uterine cancers in postmenopausal women.
PMID- 28412810
TI - Ultraviolet Light Makes dGMP Floppy: Femtosecond Stimulated Raman Spectroscopy of
2'-Deoxyguanosine 5'-Monophosphate.
AB - The ultrafast dynamics of 2'-deoxyguanosine 5'-monophosphate after excitation
with ultraviolet light has been studied with femtosecond transient absorption
(TA) and femtosecond stimulated Raman spectroscopy (FSRS). TA kinetics and
transient anisotropy spectra reveal a rapid relaxation from the Franck-Condon
region, producing an extremely red-shifted stimulated emission band at ~440 nm
that is formed after 200 fs and subsequent relaxation for 0.8-1.5 ps, consistent
with prior studies. Viscosity dependence shows that the initial relaxation,
before 0.5 ps, is the same in water or viscous glycerol/water mixtures, but after
0.5 ps the dynamics significantly slow down in a viscous solution. This indicates
that large amplitude structural changes occur after 0.5 ps following
photoexcitation. FSRS obtained with both 480 and 600 nm Raman pump pulses observe
very broad Raman peaks at 509 and 1530 cm-1, as well as a narrower peak at 1179
cm-1. All of the Raman peaks decay with 0.7-1.3 ps time constants. The 1530 cm-1
peak also shows an increasing inhomogeneous linewidth over the first 0.3 ps. Our
TA and FSRS data are consistent with a structurally inhomogeneous population in
the S1 (La) state and, in particular, with previous theoretical models in which
out-of-plane distortion at C2 and the amine move the molecule toward a conical
intersection with the ground state. These FSRS data are the first to directly
observe the structural inhomogeneity imparted upon the excited-state population
by the broad, flat potential energy surface of the S1 (La) state.
PMID- 28412811
TI - Two-Dimensional Metal-Free Organic Multiferroic Material for Design of
Multifunctional Integrated Circuits.
AB - Coexistence of ferromagnetism and ferroelectricity in a single 2D material is
highly desirable for integration of multifunctional units in 2D material-based
circuits. We report theoretical evidence of C6N8H organic network as being the
first 2D organic multiferroic material with coexisting ferromagnetic and
ferroelectric properties. The ferroelectricity stems from multimode proton
transfer within the 2D C6N8H network, in which a long-range proton-transfer mode
is enabled by the facilitation of oxygen molecule when the network is exposed to
the air. Such oxygen-assisted ferroelectricity also leads to a high Curie
temperature and coupling between ferroelectricity and ferromagnetism. We also
find that hydrogenation and carbon doping can transform the 2D g-C3N4 network
from an insulator to an n-type/p-type magnetic semiconductor with modest bandgap.
Akin to the dopant induced n/p channels in silicon wafer, a variety of dopant
created functional units can be integrated into the g-C3N4 wafer by design for
nanoelectronic applications.
PMID- 28412813
TI - Singlet Oxygen Detection on a Nanostructured Porous Silicon Thin Film via
Photonic Luminescence Enhancements.
AB - Because reactive oxygen species are involved in a range of pathologies,
developing analytical tools for this group of molecules opens new vistas for
biomedical diagnostics. Herein, we fabricate a porous silicon microcavity (pSiMC)
functionalized with luminescent singlet oxygen (1O2) probe EuA ((Eu(III)-2,2',2"
(10-(2-((4-(2-((4-(2-((anthracen-9-ylmethyl)amino)ethyl)-1H-1,2,3-triazol-1
yl)amino)-2-oxoethyl)-2-oxo-1,2-dihydroquinolin-7-yl)amino)-2-oxoethyl)-1,4,7,10
tetraazacyclododecane-1,4,7-triyl)triacetic acid) as proof of concept of an
optical sensor for reactive oxygen species. We characterize each surface
modification step of the pSiMC by means of FTIR and X-ray photoelectron
spectroscopy as well as by determining the optical shifts of the resonance
wavelength of the pSiMC. The luminescence signal upon detection of 1O2 on the EuA
modified pSiMC is enhanced ~2-fold compared to that of a single layer and a
detuned microcavity. The sensing performance of the EuA probe is improved
significantly on the pSiMC compared to that in aqueous solution, giving a limit
of 1O2 detection of 3.7 * 10-8 M.
PMID- 28412812
TI - An IonStar Experimental Strategy for MS1 Ion Current-Based Quantification Using
Ultrahigh-Field Orbitrap: Reproducible, In-Depth, and Accurate Protein
Measurement in Large Cohorts.
AB - In-depth and reproducible protein measurement in many biological samples is often
critical for pharmaceutical/biomedical proteomics but remains challenging. MS1
based quantification using quadrupole/ultrahigh-field Orbitrap (Q/UHF-Orbitrap)
holds great promise, but the critically important experimental approaches
enabling reliable large-cohort analysis have long been overlooked. Here we
described an IonStar experimental strategy achieving excellent quantitative
quality of MS1 quantification. Key features include: (i) an optimized, surfactant
aided sample preparation approach provides highly efficient (>75% recovery) and
reproducible (<15% CV) peptide recovery across large cell/tissue cohorts; (ii) a
long column with modest gradient length (2.5 h) yields the optimal balance of
depth/throughput on a Q/UHF-Orbitrap; (iii) a large-ID trap not only enables
highly reproducible gradient delivery as for the first time observed via real
time conductivity monitoring, but also increases quantitative loading capacity by
>8-fold and quantified >25% more proteins; (iv) an optimized HCD-OT markedly
outperforms HCD-IT when analyzing large cohorts with high loading amounts; (v)
selective removal of hydrophobic/hydrophilic matrix components using a novel
selective trapping/delivery approach enables reproducible, robust LC-MS analysis
of >100 biological samples in a single set, eliminating batch effect; (vi) MS1
acquired at higher resolution (fwhm = 120 k) provides enhanced S/N and
quantitative accuracy/precision for low-abundance species. We examined this
pipeline by analyzing a 5 group, 20 samples biological benchmark sample set, and
quantified 6273 unique proteins (>=2 peptides/protein) under stringent cutoffs
without fractionation, 6234 (>99.4%) without missing data in any of the 20
samples. The strategy achieved high quantitative accuracy (3-6% media error), low
intragroup variation (6-9% media intragroup CV) and low false-positive biomarker
discovery rates (3-8%) across the five groups, with quantified protein abundances
spanning >6.5 orders of magnitude. Finally, this strategy is straightforward,
robust, and broadly applicable in pharmaceutical/biomedical investigations.
PMID- 28412814
TI - Fe3O4@PANI Hybrid Shell as a Multifunctional Support for Au Nanocatalysts with a
Remarkably Improved Catalytic Performance.
AB - Au@Fe3O4@PANI hybrid shells with controllable polyaniline (PANI) coatings as
advanced supported catalysts have been fabricated. Specifically, Fe3O4 and Au
nanoparticles were assembled on SiO2 templates, followed by conducting polymer
PANI coating, leading to the formation of Au@Fe3O4@PANI hybrid shells after the
template removal. The resultant supported Au nanocatalysts not only maintain
hollow structures but also possess high saturation magnetization (65.46 emu/g).
Catalytic tests toward the reduction of 4-nitrophenol in the presence of NaBH4
indicate that PANI and Fe3O4 not only endow high stability and recyclability but
also can largely improve the catalytic activity of Au nanoparticles because of
their synergetic effects. It is believed that Fe3O4@PANI hybrid shells can be
regarded as multifunctional supports for noble metal nanocatalysts with a
remarkably improved catalytic performance.
PMID- 28412816
TI - Metal-Free Electrophilic Phosphination/Cyclization of Alkynes.
AB - A metal-free electrophilic phosphination reaction has been developed.
Electrophilic phosphorus species generated in situ from secondary phosphine
oxides and Tf2O smoothly couple with alkynes possessing pendant nucleophiles to
afford the corresponding phosphinated cyclization products in good yield.
Preliminary NMR studies show that phosphirenium species may be involved as
intermediates of the cyclization reactions.
PMID- 28412815
TI - High-Throughput Analysis of Intact Human Proteins Using UVPD and HCD on an
Orbitrap Mass Spectrometer.
AB - The analysis of intact proteins (top-down strategy) by mass spectrometry has
great potential to elucidate proteoform variation, including patterns of post
translational modifications (PTMs), which may not be discernible by analysis of
peptides alone (bottom-up approach). To maximize sequence coverage and
localization of PTMs, various fragmentation modes have been developed to produce
fragment ions from deep within intact proteins. Ultraviolet photodissociation
(UVPD) has recently been shown to produce high sequence coverage and PTM
retention on a variety of proteins, with increasing evidence of efficacy on a
chromatographic time scale. However, utilization of UVPD for high-throughput top
down analysis to date has been limited by bioinformatics. Here we detected 153
proteins and 489 proteoforms using UVPD and 271 proteins and 982 proteoforms
using higher energy collisional dissociation (HCD) in a comparative analysis of
HeLa whole-cell lysate by qualitative top-down proteomics. Of the total detected
proteoforms, 286 overlapped between the UVPD and HCD data sets, with 68% of
proteoforms having C scores greater than 40 for UVPD and 63% for HCD. The average
sequence coverage (28 +/- 20% for UVPD versus 17 +/- 8% for HCD, p < 0.0001) was
found to be higher for UVPD than HCD and with a trend toward improvement in q
value for the UVPD data set. This study demonstrates the complementarity of UVPD
and HCD for more extensive protein profiling and proteoform characterization.
PMID- 28412817
TI - Impact of Microcystis aeruginosa Exudate on the Formation and Reactivity of Iron
Oxide Particles Following Fe(II) and Fe(III) Addition.
AB - Impact of the organic exudate secreted by a toxic strain of Microcystis
aeruginosa on the formation, aggregation, and reactivity of iron oxides that are
formed on addition of Fe(II) and Fe(III) salts to a solution of the exudate is
investigated in this study. The exudate has a stabilizing effect on the particles
formed with decreased aggregation rate and increased critical coagulant
concentration required for diffusion-limited aggregation to occur. These results
suggest that the presence of algal exudates from Microcystis aeruginosa may
significantly influence particle aggregation both in natural water bodies where
Fe(II) oxidation results in oxide formation and in water treatment where Fe(III)
salts are commonly added to aid particle growth and contaminant capture. The
exudate also affects the reactivity of iron oxide particles formed with exudate
coated particles undergoing faster dissolution than bare iron oxide particles.
This has implications to iron availability, especially where algae procure iron
via dissolution of iron oxide particles as a result of either reaction with
reducing moieties, light-mediated ligand to metal charge transfer and/or reaction
with siderophores. The increased reactivity of exudate coated particles is
attributed, for the most part, to the smaller size of these particles, higher
surface area and increased accessibility of surface sites.
PMID- 28412818
TI - Transparent Ethenylene-Bridged Polymethylsiloxane Aerogels: Mechanical
Flexibility and Strength and Availability for Addition Reaction.
AB - Transparent, low-density ethenylene-bridged polymethylsiloxane [Ethe-BPMS,
O2/2(CH3)Si-CH?CH-Si(CH3)O2/2] aerogels from 1,2-bis(methyldiethoxysilyl)ethene
have successfully been synthesized via a sol-gel process. A two-step sol-gel
process composed of hydrolysis under acidic conditions and polycondensation under
basic conditions in a liquid surfactant produces a homogeneous pore structure
based on cross-linked nanosized colloidal particles. Visible-light transmittance
of the aerogels varies with the concentration of the base catalyst and reaches as
high as 87% (at a wavelength of 550 nm for a 10 mm thick sample). Gelation and
aging temperature strongly affect the deformation behavior of the resultant
aerogels against uniaxial compression, and the obtained aerogels prepared at 80
degrees C show high elasticity after being unloaded. This highly resilient
behavior is primarily derived from the rigidity of ethenylene groups, which is
confirmed by a comparison with other aerogels with similar molecular structures,
ethylene-bridged polymethylsiloxane and polymethylsilsesquioxane. Applicability
of the addition reaction using a Diels-Alder reaction of benzocyclobutene has
also been investigated, revealing that a successful addition takes place on the
ethenylene linkings, which is verified using Raman and solid-state NMR
spectroscopies. Insights into the effect of molecular structure on mechanical
properties and the availability of surface functionalization provided in this
study are important for realizing transparent aerogels with the desired
functionality.
PMID- 28412819
TI - Structural and Spectroscopic Characterization of TPGS Micelles: Disruptive Role
of Cyclodextrins and Kinetic Pathways.
AB - The aggregation and structure of d-alpha-tocopheryl polyethylene glycol succinate
micelles, TPGS-1000, an amphiphilic derivative of vitamin E, were characterized
using scattering and spectroscopic methods, and the impact of different
cyclodextrins (CDs) on the self-assembly was investigated, with the view of
combining these two versatile pharmaceutical excipients in drug formulations.
Combined small-angle neutron scattering (SANS), dynamic light scattering, and
time-resolved and steady-state fluorescence emission experiments revealed a core
shell architecture with a high aggregation number (Nagg ~ 100) and a highly
hydrated poly(ethylene oxide) corona (~11 molecules of solvent per ethylene oxide
unit). Micelles form gradually, with no sharp onset. Structural parameters and
hydration of the aggregates were surprisingly stable with both temperature and
concentration, which is a critical advantage for their use in pharmaceutical
formulations. CDs were shown to affect the self-assembly of TPGS in different
ways. Whereas native CDs induced the precipitation of a solid complex
(pseudopolyrotaxane), methylated beta-CDs led to different outcomes: constructive
(micellar expansion), destructive (micellar rupture), or no effect, depending on
the number of substituents and whether the substitution pattern was regular or
random on the rims of the macrocycle. Time-resolved SANS studies on mixtures of
TPGS with regularly dimethylated beta-CD (DIMEB), which ruptures the micelles,
revealed an almost instantaneous demicellization (<100 ms) and showed that the
process involved the formation of large aggregates whose size evolved over time.
Micellar rupture is caused by the formation of a TPGS-DIMEB inclusion complex,
involving the incorporation of up to three macrocycles on the tocopherol, as
shown by proton nuclear magnetic resonance (NMR) and ROESY NMR. Analysis of NMR
data using Hill's equation revealed that the binding is rather cooperative, with
the threading of the CD favoring the subsequent inclusion of additional CDs on
the aliphatic moiety.
PMID- 28412820
TI - Systems Toxicology II: A Special Issue.
PMID- 28412822
TI - Determinants of Lifestyle Behavior in Iranian Adults with Prediabetes: Applying
the Theory of Planned Behavior.
AB - OBJECTIVE: Prediabetic condition can lead to development of type 2 diabetes,
especially in individuals who do not adhere to a healthy lifestyle. The aim of
the present study was to investigate the socio-cognitive factors using the Theory
of Planned Behavior (TPB) that may be associated with the choice of lifestyle in
prediabetic patients. METHODS: A prospective study with one-month follow up was
designed to collect data from 350 individuals with prediabetic conditions. A
questionnaire was used to collect the information, including demographic
variables, exercise behavior, food consumption, as well as the constructs of the
TPB (attitude, subjective norms, perceived behavioral control, and behavioral
intention) regarding physical activity and dietary choice. The correlations
between TPB variables and the dependent variables (dietary choice, physical
activity) were assessed using Spearman correlation and multiple regression
models. RESULT: In total, 303 people participated. The mean age of the
participants was 53.0 (SD 11.5) years and 42% were males. Significant
correlations were found between all TPB constructs and both dependent variables
(healthy eating and exercise behaviors) both at baseline and after one month (P <
0.01). The predictive validity of the TPB over time was proved for both dependent
variables where past and future behaviors were significantly correlated with the
constructs. Nearly 87% of the variance in exercise behavior and 72% of the
variance in healthy eating behavior were explainable by TPB constructs.
CONCLUSION: The TPB may be a useful model to predict behaviors of physical
activity and dietary choice among prediabetic people. Therefore, it may be used
to monitor lifestyle modification to prevent development of diabetes among people
with prediabetic conditions.
PMID- 28412823
TI - Epidemiologic Study of Opium Use in Pars Cohort Study: A Study of 9000 Adults in
a Rural Southern Area of Iran.
AB - BACKGROUND: Opium is one of the most common substances used worldwide with
variable epidemiologic features in different regions. This study was performed in
southern Iran, to find the epidemiology of opium use and its association with
different factors and diseases. METHODS: This cross-sectional study was performed
on baseline data extracted from Pars Cohort Study performed in Valashahr, a rural
area in southern Iran. For any subject, information was collected about
demographic factors, some common diseases including heart disease, stroke and
hypertension and the state of using opium, other substances and cigarettes.
RESULTS: There were 4276 males and 4988 females, with a mean age of 52.6 +/- 9.7
years of whom 8.4% reported opium use (17.3% of males and 0.7% of females). In
men, the history of stroke and heart disease were significantly more common in
opium users (12.6% vs. 8.8%, P = 0.001 and 2.8% vs. 1.5%, P = 0.01, respectively)
while the history of hypertension was significantly more common in non-opium
users (7.8% vs. 10.3%, P = 0.04). Younger age, male gender, being non-married and
positive history of joint pain, cigarette smoking and alcohol consumption were
the factors associated with opium use. CONCLUSION: Opium use is common in non
married men who have a positive history of cigarette smoking and alcohol
consumption in the rural population of southern Iran. It is associated with
increased risk of heart disease and stroke and decreased risk of hypertension in
males. Global interventional and preventive measures are required to control this
complicated social problem.
PMID- 28412824
TI - Assessment of Lean Patients with Non-alcoholic Fatty Liver Disease in a Middle
Income Country; Prevalence and Its Association with Metabolic Disorders: A Cross
sectional Study.
AB - BACKGROUND: Recent data has proven that the WHO (world health organization) cut
off for obesity is not applicable to the Asian population. This study aims to
estimate the prevalence of lean NAFLD (non-alcoholic fatty liver disease) in the
capital of Iran and extract probable predictors for this growing health issue in
this population. METHODS: This is a population-based cross-sectional study on
apparently healthy subjects over 18 years of age. The participants were
interviewed for baseline demographic and clinical information. They were
subsequently referred for physical examination and blood sampling. NAFLD was
diagnosed using abdominal ultrasonography by a single expert radiologist.
RESULTS: Of 927 eligible participants who entered the study, 314 were lean; BMI
(body mass index) <25 kg/m2. The prevalence of NAFLD was 17.52% (95% Exact CI:
13.48%-22.18%). BMI, SBP (systolic blood pressure), DBP (diastolic blood
pressure), total cholesterol, HDL (high-density lipoprotein), LDL (low-density
lipoprotein) and triglyceride were significantly different in patients with
NAFLD. In the final multiple analysis, higher levels of triglyceride, upper SBP
and higher BMI even in the range of less than 25 kg/m2 were independent
predictors of NAFLD in lean participants. In lean participants with more
components of metabolic syndrome, the prevalence of NAFLD increased significantly
(all P < 0.01). BMI cut-offs in men and women along with waist circumference cut
off in men could significantly predict the presence of NAFLD in lean patients.
After comparing these values, McNemar test showed that BMI cut-offs are more
robust than waist circumference cut-offs for predicting the presence of NAFLD in
lean subjects (P < 0.01). CONCLUSION: The prevalence of NAFLD in lean subjects in
a sample of Iranian population is 17.52%. Hypertriglyceridemia, higher SBP, and
higher BMI especially over 23.2 are independent factors associated with the
presence of NAFLD in lean subjects.
PMID- 28412825
TI - Family Dinner Frequency is Inversely Related to Mental Disorders and Obesity in
Adolescents: the CASPIAN-III Study.
AB - PURPOSE: Family dinner is a proxy of family connectedness that may affect mental
health. The present study aimed to examine the associations of frequency of
family dinner with mental disorders and obesity in a nationally-representative
sample of Iranian adolescents. METHODS: A total of 5528 Iranians adolescents aged
10-18 years were enrolled in 2009-2010 in the third survey of a national
surveillance program, entitled Childhood and Adolescence Surveillance and
Prevention of Adult Non-communicable disease (CASPIAN-III) study. The frequency
of family dinner meal was assessed. Mental health assessments were done as part
of the World Health Organization-Global School-based Student Health Survey. The
odds of having mental disorders and obesity were assessed by logistic regression.
RESULTS: No significant difference was found in dietary intake between family
dinner consumers (>=5 times (night)/wk) and skippers (<5 times/wk); however, they
were more likely to consume breakfast and had higher meal frequency. After
controlling for some confounders, dinner consumers had lower odds for all types
of mental disorders (OR = 0.55; 95% CI = 0.47-0.64), anxiety (OR = 0.47; 95% CI =
0.4-0.54), insomnia (OR = 0.6; 95% CI = 0.53-0.7), and confusion (OR = 0.7; 95%
CI = 0.6-0.86), as well as the body mass index- z score (OR = 0.78; 95% CI = 0.73
0.84). CONCLUSION: The current study showed an inverse relationship between the
frequency of family dinner consuming and mental disorders and obesity in a
nationally-representative sample of Iranian adolescents. Such simple
recommendations for consuming family dinner for families may be feasible,
sustainable, and effective for health promotion and disease prevention.
PMID- 28412826
TI - Prevalence of Human T-lymphotropic virus type 1 (HTLV-1) Infection in Patients
with Hematologic Disorders and Non-Hematologic Malignancies in a Tertiary
Referral Hospital.
AB - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) was the first retrovirus
identified in human. The current evidence is quite scarce regarding the potential
role of HTLV-1 in pathogenesis of hematologic disorders and non-hematologic
malignancies. OBJECTIVES: The aim of this study is to evaluate the prevalence of
HTLV-1 infection in patients with hematologic disorders and non-hematologic
malignancies. METHODS: This cross-sectional study was conducted on 505 cases of
definite diagnosis of hematologic disorders including malignancies as well as non
malignant disorders such as polycythemia and myelofibrosis and non-hematologic
malignancies referred to the hematology and medical oncology ward at Army
Hospital 501 from January 2015 to January 2016. A 3-mL blood specimen was
collected from each patient and tested for the presence of anti-HTLV-1 antibodies
using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS
software package version 19 (IBM, New York, USA). Data are presented as mean +/-
SD if normally distributed and otherwise as median (range). RESULTS: Totally, 242
(48%) males and 263 (52%) females with a mean +/- SD age of 52.09 +/- 16.24 were
enrolled in this study. In total, there were 9 (1.78%) cases positive for HTLV-1
infection including 4 males and 5 females. Seven out of 287 (2.4%) patients with
hematologic disorders were infected by HTLV-1. In non-hematologic malignancies, 2
out of 211 cases were positive (0.9%). There was no HTLV-1 positive case in 7
patients with both hematologic and non-hematologic disorders. The difference in
HTLV-1 infection prevalence between patients with hematologic disorders and non
hematologic malignancies was not statistically significant different (P = 0.31).
There was no association between sex and transfusion history with HTLV-1
infection in this population (P = 0.9 and 0.7, respectively). CONCLUSIONS: Our
study revealed that the prevalence of HTLV-1 in hematologic disorders is higher
than the general population. Further larger prospective studies are recommended
to corroborate the current evidence.
PMID- 28412827
TI - Challenges of Tobacco Control Program in Iran.
AB - BACKGROUND: This study assessed the status of cigarette marketing in Iran as well
as the attitude of smokers toward smoking and the policies and tobacco control
programs in the country. METHODS: This cross-sectional study was conducted on
3480 volunteer smokers in six provinces, using a stratified cluster random
sampling method. The study population consisted of smokers who used at least one
cigarette per day. The data collection tool was an anonymous self-administered
questionnaire including basic information and 20 five-choice questions related to
participants' attitude toward smoking habits (Cronbach's alpha; 79.73%.).
RESULTS: The majority (66.9%) of participants started smoking at the age of 10 to
19 years and 61.1% used foreign cigarettes. Of 160 marketed brands, 38 (23.8%)
were domestic and 122 (76.2%) were foreign, including 63 (39.3%) imported and 59
(36.9%) smuggled brands. Being tempted (25.0%), getting nervous (24.1%), and
seeking euphoria (24.1%) were the most common reasons for restarting cigarette
smoking after cessation. The majority of participants believed that smoking in
public places was a violation of the rights of others and smoking should be
avoided in such places. CONCLUSION: Smoking prevention programs should focus on
adolescents as the most vulnerable age group. Raising the retail price of tobacco
products through increasing taxes can reduce consumption, particularly among
first starters and youth. However, increasing taxes and prices of tobacco
products may be effective when simultaneous effective measures are implemented to
eliminate all kinds of illicit trade in all forms of tobacco products.
PMID- 28412828
TI - Magnetic Resonance Angiographic Study of Anatomic Variations of the Circle of
Willis in a Population in Tehran.
AB - BACKGROUND AND OBJECTIVES: The circle of Willis, an anastomotic polygon at the
base of the brain, forms an important collateral network to maintain cerebral
blood perfusion. The aim of this study was to investigate different anatomic
variations of the circle of Willis and their prevalence. METHODS: This cross
sectional study was conducted on 525 healthy participants including 205 men and
320 women. The mean age of the patients was 51.5 years. Three-dimensional time-of
flight magnetic resonance angiography (3D-TOF MRA) technique was used. Vascular
variations in the anterior and posterior parts of the circle were evaluated.
RESULTS: The findings show that the complete circle of Willis was visible in a
small number of patients. The circle of Willis had a complete vascular structure
in 20.9% of the patients. The anterior part of the circle of Willis had a
complete structure in 80.95% of the cases, while the posterior part had a
complete structure in 20.95% of the cases. CONCLUSION: We observed wide
variations in the circle of Willis configuration in our study. Similar to other
studies, most variations are related to the posterior part of the circle of
Willis. Absence of bilateral posterior communicating artery variation is more
common than other types of variations in this population.
PMID- 28412829
TI - EGFR Expression in Patients with Esophageal Squamous Cell Carcinoma and its
Association with Pathologic Response to Preoperative Chemoradiotherapy: A Study
in Northeastern Iran.
AB - INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all
esophageal cancers worldwide. It is the most common histological type of
esophageal carcinoma in low-resource countries. ESCC is prevalent in Asian
countries, accounting for more than 95% of esophageal cancers. The epidermal
growth factor receptor (EGFR) is involved in cancer development, as its gene is
often mutated and/or amplified in cancer cells. According to recent statistics,
esophageal cancer is the eighth most common cancer in Iran. METHODS: In this
retrospective study, we assessed EGFR overexpression, using immunohistochemistry
(IHC) in 68 patients with ESCC, undergoing neoadjuvant chemoradiotherapy and
esophagectomy in 2011-2014. The treatment protocol included external beam
radiotherapy (40 Gy), concomitant with cisplatin 20mg/m2 and 5- fluorouracil (5
FU) 1000 mg/m2 for 4 consecutive days during the first and fourth weeks of
treatment. To compare the two groups (EGFR positive and negative) in terms of
complete pathologic response, Chi-square test was performed using SPSS version
16. RESULTS: The median age of the patients was 59 years (range: 27-70 years),
with a female-to-male ratio of 1.06. Overall, 70% of the subjects showed EGFR
overexpression. Complete pathologic response to neoadjuvant treatment was
significantly higher in EGFR-positive patients (40% vs. 15.8%, P = 0.05). In all
cases, 1- and 3-year overall survival rates were 86.6% +/- 4.1 and 48% +/- 6.9,
respectively. The 1- and 3-year disease free survival rates were calculated as
71.8% +/- 5.4 and 44.3% +/- 6.5, respectively. The overall survival rate was
relatively higher in cases with EGFR overexpression, although the difference was
not statistically significant (5-year survival rate: 47.9 +/- 8.2 vs. 30.9 +/-
13, P = 0.23). CONCLUSION: EGFR overexpression was reported in the majority of
patients with ESCC in northeastern Iran. Moreover, EGFR overexpression was
significantly associated with complete pathologic response.
PMID- 28412830
TI - Expression and Immunogenicity of VP40 Protein of ZEBOV.
AB - BACKGROUND: EBOV outbreaks continue to threaten the world due to the absence of
effective vaccines and therapeutics. Easy-to-use and rapid diagnostic tests for
EBOV are highly desired for prevention and control of the EVD epidemic. METHODS:
Escherichia coli expression system was used to express VP40 protein of Zaire
Ebola virus (ZEBOV) as water-soluble protein upon optimization of temperature,
time, and IPTG concentration. VP40 protein was purified through Ni-NTA affinity
chromatography and applied to immunize rabbits for immunogenicity analysis.
Rabbit polyclonal antibodies against VP40 protein was produced and antibody
response was analyzed using Western blot, enzyme-linked immunosorbent assay
(ELISA), and immunoperoxidase monolayer assay (IPMA). RESULTS: Recombinant full
length VP40 protein of ZEBOV was expressed in E. coli Rosetta (DE3) cells as
water-soluble protein. Analysis of antibody responses showed that rabbit
polyclonal antibodies against VP40 protein could react specifically with this E.
coli-expressed protein in Western blot and ELISA, and antibody titers in ELISA
reached 1:25600. Besides, the produced rabbit polyclonal antibodies bound to VP40
proteins eukaryotically expressed by transfecting pcDNA-eGFP-VP40 into BHK-21
cells in IPMA. CONCLUSION: These results show that the prokaryotically expressed
VP40 protein has high immunogenicity and can be used as diagnostic antigen in
ELISA and other immunoassays. The strategy used in this study might be a
potential way for preparing diagnostic agents for prevention and control of
exotic diseases.
PMID- 28412831
TI - Unfair Judgment against Iranian Scientists.
PMID- 28412832
TI - Gondeshapur Revisited; What Historical Evidence?
AB - In recent years, in European academic circles, there has been a trend to dismiss
Gondeshapur as a myth perpetrated by the Bokhtishu family in early Islamic era,
despite many historiographical attestations. The writings of Islamic historians
such as Al-Qifti and Ibn Abi Usaibia have been discounted as exaggerations by non
contemporary historians, and the lack of primary Pahlavi sources blamed for
historical hyperbole. In this essay, I have attempted to show through primary
Syriac Christian texts, that there was both a medical school and a bimarestan in
Gondeshapur in pre-Islamic Sassanid era, and that Galenic medical texts had been
translated and taught in that institution.
PMID- 28412833
TI - Medical Concepts in Ferdowsi's Shahnameh.
PMID- 28412835
TI - Validation of a Seven-Factor Structure for the Motives for Playing Drinking Games
Measure.
AB - Playing drinking games can be characterized as a high-risk drinking activity
because games are typically designed to promote heavy alcohol consumption. While
research suggests that young adults are motivated to play drinking games for a
variety of reasons (e.g., for thrills/fun, for the competition), the Motives for
Playing Drinking Games measure has received limited empirical attention. We
examined the psychometric properties of this measure with a confirmation sample
of young adults recruited from Amazon's MTurk ( N = 1,809, ages 18-25 years, 47%
men; 41% not currently enrolled in college) and a validation sample of college
students ( N = 671; ages 18-23 years; 26% men). Contrary to the 8-factor model
obtained by Johnson and Sheets in a study published in 2004, examination of the
factor structure with our confirmation sample yielded a revised 7-factor model
that was invariant across race/ethnicity and college student status. This model
was also validated with the college student sample. In the confirmation sample,
enhancement/thrills and sexual pursuit motives for playing drinking games were
positively associated with gaming frequency/consumption and negative gaming
consequences. Furthermore, conformity motives for playing drinking games were
positively associated with negative gaming consequences, while competition
motives were positively associated with gaming frequency. These findings have
significant implications for research and prevention/intervention efforts.
PMID- 28412836
TI - Reducing Time to Internal Medicine Consultation in the ED of a Community-Based
Hospital: A Commentary on a Quality Improvement Initiative.
PMID- 28412837
TI - Reliability and Validity of START and LSI-R Assessments in Mental Health Jail
Diversion Clients.
AB - Risk assessment instruments are increasingly used in mental health jail diversion
programs. This study examined the reliability and validity of Short-Term
Assessment of Risk and Treatability (START) and Level of Service Inventory
Revised (LSI-R) assessments overall and by client race. Research assistants
completed START and LSI-R assessments for 95 diversion clients. Arrests and jail
days were collected via official records and self-report 3, 6, 9, 12, and 18
months after baseline. Assessments demonstrated good interrater reliability and
convergent validity. START strength total scores and LSI-R risk estimates were
the strongest predictors of recidivism. Total scores and risk estimates did not
differ as a function of client race, but there were some differences in accuracy
of START vulnerability and LSI-R total scores and risk estimates in predicting
jail days (but not arrests), over shorter follow-ups. No such differences were
found for START strength total scores across any follow-up period or recidivism
measure.
PMID- 28412838
TI - Self-reported sleep complaints are associated with adverse health outcomes: cross
sectional analysis of the 2002/03 New Zealand Health Survey.
AB - OBJECTIVE: The aim was to investigate the prevalence of self-reported sleep
complaints in New Zealand adults and determine the independent association of
sleep complaints with adverse health outcomes. DESIGN: We used 2002/03 New
Zealand Health Survey data (n = 12,500 adults, >=15 years). The prevalence of
self-reported sleep complaints was estimated by ethnicity. The relationship
between sleep complaints and mental health, physical health and health risk
behaviors were investigated using multivariable logistic regression models.
RESULTS: The prevalence of each sleep complaint measure was highest for the
indigenous Maori population (23.6% reported 'any' sleep complaint; 10.3% reported
multiple sleep complaints). Reporting 'any' sleep complaint was associated with
higher odds of poorer mental health, diagnosed high blood pressure, diagnosed
diabetes, diagnosed heart disease, poor/fair self-rated health, obesity, current
smoking, and hazardous drinking. CONCLUSION: The higher prevalence of sleep
complaints among Maori and the consistent association with poor health suggests a
potential role for suboptimal sleep in ethnic health inequities.
PMID- 28412839
TI - Awareness and Knowledge of Ovarian Cancer Symptoms and Risk Factors: A Survey of
Jordanian Women.
AB - Ovarian cancer accounts for 3% of all female cancers and has a high mortality
rate among gynecological malignancies. Early diagnosis carries a high survival
rate of 93%. So, this study was carried out to assess the knowledge and awareness
of Jordanian women about ovarian cancer symptoms and risk factors. A cross
sectional survey design was used; 896 women completed the survey. The mean of
total symptoms recognized was low at level of 3.2 ( SD = 2.7) out of 10. The
three highest known symptoms among women were as follows: extreme fatigue
(43.2%), back pain (42.4%), and persistent pain in pelvic area (40.7%). The most
commonly known risk factor was smoking (68.4%), followed by having ovarian
cyst(s) (59.7%). Hence, with the absence of an effective screening program, a
national awareness campaign is urgently needed to improve the public's
understanding of symptoms and risk factors and increasing women's confidence in
symptom recognition.
PMID- 28412840
TI - Anti-proliferative and pro-apoptotic effects of cinobufagin on human breast
cancer MCF-7 cells and its molecular mechanism.
AB - Cinobufagin (CBF) is an active ingredient isolated from Venenum Bufonis extracted
and dried from the secretory glands of Bufo gargarizans Cantor. The purpose of
the study was to investigate the effects and underlying mechanisms of CBF on
human breast cancer MCF-7 cells in vitro. Our results showed that CBF exhibited
obvious cytotoxicity on MCF-7 cells in a dose- and time-dependent manner, as
indicated by CCK-8 assays. Also, Hoechst 33258 staining and flow cytometry assays
showed that CBF strongly induced MCF-7 cell apoptosis and G1 phase arrest. In
addition, further molecular mechanistic investigation demonstrated that
cinobufagin significantly increased Bax expression, decreased Bcl-2 expression
level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein
Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays. Taken
together, our data confirm that CBF inhibits growth and triggers apoptosis of MCF
7 cells by affecting the expression of Bax and Bcl-2 in vitro.
PMID- 28412841
TI - A new pyranoxanthone from Garcinia nervosa.
AB - Phytochemical studies on the stem bark of Garcinia nervosa has resulted in the
discovery of one new pyranoxanthone derivative, garner xanthone (1) and five
other compounds, 1,5-dihydroxyxanthone (2), 6-deoxyisojacareubin (3), 12b-hydroxy
des-D-garcigerrin A (4) stigmasterol (5), and beta-sitosterol (6). The structures
of these compounds were elucidated with the aid of spectroscopic techniques, such
as NMR and MS. The crude extracts of the plant were assessed for their
antimicrobial activity.
PMID- 28412842
TI - Four new Sesquiterpenoids from Sphaeranthus indicus.
AB - Isolation and characterisation of two new eudesmanolides, 5alpha-hydroperoxy
7alpha-hydroxy-isosphaerantholide (1) and (11alpha,13-dihydro-7alpha
hydroxyfrullanolide-13-yl)-adenine (2) from the flower heads of Sphaeranthus
indicus are described. In addition, 5alpha-hydroxy-isosphaerantholide (3) and
11alpha,13-dihydro-eudesman-3,5,7-triene-6alpha-12-olide (4) are reported first
time as a metabolite of S. indicus and as a natural product, respectively. The
structures of these compounds were established from rigorous analysis of their
high-resolution mass, IR, UV, 1H NMR, 13C NMR and 2D NMR spectral data.
PMID- 28412843
TI - Continuous ECG Monitoring in Patients With Acute Coronary Syndrome or Heart
Failure: EASI Versus Gold Standard.
AB - The purpose of the study was to compare the EASI system with the standard 12-lead
surface electrocardiogram (ECG) for the accuracy in detecting the main
electrocardiographic parameters (J point, PR, QT, and QRS) commonly monitored in
patients with acute coronary syndromes or heart failure. In this observational
comparative study, 253 patients who were consecutively admitted to the coronary
care unit with acute coronary syndrome or heart failure were evaluated. In all
patients, two complete 12-lead ECGs were acquired simultaneously. A total of
6,072 electrocardiographic leads were compared (3,036 standard and 3,036 EASI).
No significant differences were found between the investigate parameters of the
two measurement methods, either in patients with acute coronary syndrome or in
those with heart failure. This study confirmed the accuracy of the EASI system in
monitoring the main ECG parameters in patients admitted to the coronary care unit
with acute coronary syndrome or heart failure.
PMID- 28412844
TI - Compounds with inhibitory activity on peristalsis from the seeds of Holarrhena
antidysenterica.
AB - Eight compounds were isolated from the seeds of Holarrhena antidysenterica
Wall.ex A.DC. On the basis of physico-chemical properties and spectroscopic data,
holarrhenanan (1) was identified as a new compound, compounds 2-3 were isolated
from H. antidysenterica for the first time, and five known compounds were also
obtained. Inhibitory effects of some compounds and extracts to the intestinal
peristalsis were evaluated. Results showed that the extracts and compounds 4, 6
exhibited remarkable inhibitory effects with tension inhibition rate of 32.77,
32.77% and amplitude inhibition rate of 59.51, 55.98%, respectively on the vitro
rabbit intestinal peristalsis.
PMID- 28412845
TI - Fetal and maternal temperatures during labor and delivery: a prospective
descriptive study.
AB - OBJECTIVE: The objective of this study is to study the fetal scalp temperature
(FST) and maternal axillary temperature (MAT) during vaginal delivery relative to
progression of labor, uterine contractions (UC) and epidural analgesia (EDA), and
to construct normal temperature reference ranges related to stage of labor.
MATERIAL AND METHODS: Temperatures were recorded continuously in labor of 132
women with a bi-metal temperature sensor attached to the axilla (MAT) and a
similar sensor mounted in a scalp electrode (FST). The temperature data were
stored electronically and analyzed offline at cervical dilatations of 2-3, 5, 7
8, and 10 cm, and at full retraction. The FST was read before, at increasing, at
peak, at decreasing, and after UC. The MAT and FST curves were compared with
mixed-effect models statistics for repeated measurements. A two-tailed p <.05 was
considered significant. RESULTS: The FST did not vary during UC (p = .24). Both
FST and MAT increased linearly by progression of labor (both p < .001). The
increases in temperatures were greater with EDA than without (p < .001).
CONCLUSIONS: During UC, the FST showed no alteration. Both FST and MAT increased
significantly by progression of labor, and significantly more in the presence of
EDA. The presented normal temperature reference ranges can be used for future
research.
PMID- 28412846
TI - Changes in levator hiatus dimensions during pregnancy and after delivery in
nulliparas: a prospective cohort study using 3D transperineal ultrasound.
AB - PURPOSE: The purpose of this study was to investigate the changes that occur in
the levator ani muscle (1) during pregnancy and (2) after labor depending on the
mode of delivery in a cohort of nulliparas. MATERIALS AND METHODS: A prospective
cohort longitudinal study, consisting of 84 primiparas who were examined and
recruited in an antenatal clinic was conducted. All participants were submitted
to a real-time three-dimensional (3D) ultrasonographic evaluation of the levator
ani at (1) 12, (2) 22, and (3) 32 weeks of pregnancy (4) and 4-6 months
postdelivery. The 3D volumes were acquired and stored for an offline analysis.
RESULTS: Data from 59 women with at least two measurements were available for
analysis. 35 women were delivered vaginally and 24 via cesarean section. There
was a statistical increase in the dimensions of the levator hiatus at each
pregnancy trimester when compared to the measurements of the previous trimesters.
After vaginal delivery, hiatal dimensions increased compared to the third
trimester measurements; after cesarean section, hiatal dimensions decreased.
CONCLUSIONS: This study supports that in primiparas, the dimensions of the
levator hiatus increase significantly during pregnancy and subsequently either
increase further after vaginal delivery or decrease to the first-trimester levels
after cesarean section.
PMID- 28412847
TI - Circumcision bleeding complications: neonatal intensive care infants compared to
those in the normal newborn nursery.
AB - PURPOSE: To determine if a significant difference exists in the bleeding
complications following circumcision in neonates admitted to neonatal intensive
care unit (NICU) versus the normal newborn nursery (NNN). MATERIALS AND METHODS:
Observational cohort study of 260 infants undergoing circumcision with Gomco
clamp. Vitamin K was given to neonates at delivery. Demographic data, procedural
characteristics, bleeding complications, and interventions were recorded. The
bleeding rates of the two groups were compared using chi square. RESULTS: NICU
neonates experienced increased bleeding complications versus NNN neonates (22%
vs. 9.6%, p = .029). No differences were found regarding gestational age at
delivery, age at circumcision, and birth weight. Neonates with circumcision
performed at >=5 days of life experienced increased rates of bleeding
complications versus those performed at <=4 days (28% vs. 10.3%, p = .023). All
neonates with circumcision performed >=5 days of life were initially admitted to
the NICU. CONCLUSION: NICU neonates had increased rate of bleeding complications
following circumcision when compared to the NNN neonates. There was an increased
rate of bleeding complications in neonates who undergo circumcision at >=5 days
of life. Further research may help to determine if redosing of vitamin K or
variations in the circumcision procedure are necessary for circumcision at >4
days of life.
PMID- 28412848
TI - Proteomic profile of serum of pregnant women carring a fetus with Down syndrome
using nano uplc Q-tof ms/ms technology.
AB - INTRODUCTION: Prenatal diagnosis of Down syndrome (DS) is based on the calculated
risk of maternal age, biochemical and ultrasonographic markers and recently by
cfDNA. Differences in proteomic profiles may give an opportunity to find new
biomarkers. OBJECTIVE: Characterize proteome of serum of mothers carrying DS
fetus. MATERIAL AND METHODS: Blood serum samples of three groups of women were
obtained, (a) 10 non-pregnant, (b) 10 pregnant with healthy fetus by ultrasound
evaluation, (c) nine pregnant with DS fetus. Sample preparation was as follows:
Albumin/IgG depletion, desalting, and trypsin digestion; the process was
performed in nanoUPLC MS/MS. Data analysis was made with Mass Lynx 4.1 and
ProteinLynx Global Server 3.0, peptide and protein recognition by MASCOT
algorithm and UNIPROT-Swissprot database. RESULTS: Each group showed different
protein profiles. Some proteins were shared between groups. Only sera from
pregnant women showed proteins related to immune and clot pathways. Mothers with
DS fetus had 42 specific proteins. CONCLUSIONS: We found a different serum
protein profile in mothers carrying DS fetuses that do not reflect expression of
genes in the extra chromosome. Further studies will be necessary to establish the
role of these proteins in aneuploid fetus and analyze their possible use as
potential biomarkers.
PMID- 28412849
TI - Maternal hemodynamic changes and predictors of poor obstetric outcome in women
with rheumatic heart disease: a five-year observational study.
AB - OBJECTIVE: To assess prospectively the maternal cardiovascular hemodynamic
changes and obstetric outcome in women with rheumatic heart disease (RHD) and to
detect predictors of poor outcome. METHODS: This prospective observational study
included 204 pregnant patients with RHD who were divided into two groups;
successful pregnancy group with living fetus (n = 126) and poor obstetric outcome
group with fetal or neonatal loss (n = 78). Hemodynamic changes, maternal and
fetal outcome were assessed and recorded. RESULTS: There was a highly significant
difference between the two groups regarding disease criteria with more women
suffering from stenotic lesions (mitral and aortic), pulmonary hypertension,
previous heart failure, receiving cardiac medications and higher NYHA class (III
and IV) in the poor obstetric outcome group (p < .001). These patients were more
prone to maternal and fetal morbidity. Maternal age above 28 years, body mass
index higher than 28, mean pulmonary artery pressure higher than 50 mmHg, NYHA
class III-IV and development of heart failure or cyanosis are predictors of poor
outcome (p < .001). CONCLUSIONS: Increased maternal age and body mass index
together with NYHA class III-IV, significant pulmonary hypertension, reduced
ejection fraction and development of heart failure during pregnancy are strong
predictors of poor maternal and fetal outcome.
PMID- 28412850
TI - Assessment of hysteroscopic role in management of women with recurrent pregnancy
loss.
AB - OBJECTIVES: To assess the hysteroscopic value in the management of intrauterine
lesion in women with recurrent pregnancy loss. METHODS: This study was done in
Ain Shams Maternity Hospital after the approval of the research Ethics Committee,
during the period between August 2014 and December 2015 where 200 nonpregnant
women with a history of three or more consecutive unexplained first and second
trimester miscarriages before 20 weeks were recruited from recurrent miscarriage
clinic. A written informed consent was obtained from all women before
participation. RESULTS: This current study was conducted in Ain Shams University
Maternity Hospital during the period between August 2014 to May 2015 a total of
200 women with history of recurrent miscarriage were included in the study.
Regarding the results of this study the mean age was 30.5(5.7), the mean number
of previous abortion 3(3-5) the mean number of the first trimesteric abortion was
2 with range (2-2) the mean number of second trimesteric abortion was 2 with
range (1-2). In this study, 88% of patients were nullipara. It was also found
that hysteroscopic findings were found in 58.5%. Uterine anomalies was present in
21%, including septate uterus and intrauterine adhesion (IUAs) were present in
12.5%. Endometrial polyps were present in 8.5%, bicornute uterus in 4.5%,
unicornuate uterus in 4.5% while submucous myomas were present in 7.5%. It was
found that 48.5% need hysteroscopic intervention including 21% need septectomy
12.5% need adhesiolysis, 6.5% need myomectomy while 8.5% need polypectomy. The
study found that no statistically significant difference between patients with
normal hysteroscopic finding and patients with abnormal hysteroscopic finding as
regard age, time of previous abortion and number of previous abortion. But there
was statistically significant difference as regard number of previous delivery
and abnormal HSG. CONCLUSIONS: It appears that hysteroscopy is a useful tool in
the diagnosis and treatment of the causes of recurrent miscarriage that can be
performed safely without anesthesia in most cases. The prevalence of uterine
anomalies in patients with recurrent miscarriages is 54.5%, septate uterus is the
most common anomaly and for this reason uterine anomalies should be
systematically assessed in patients with recurrent miscarriage.
PMID- 28412851
TI - Cervical pessary in the prevention of preterm births in multiple pregnancies with
a short cervix: PRISMA compliant systematic review and meta-analysis.
AB - BACKGROUND: Preterm births occur frequently in multiple pregnancies with a short
cervix. The cervical pessary is a potential intervention for prevention of
preterm births. OBJECTIVE: To assess the effectiveness of cervical pessary in the
prevention of preterm births in multiple pregnancies with a short cervix (<25
mm). SEARCH STRATEGY: Major databases from 2006 to 20th November 2016 were
searched for relevant terms. SELECTION CRITERIA: We included randomized
controlled trials that assessed the effectiveness of cervical pessary on
pregnancy outcomes in multiple pregnancies with a short cervix. DATA COLLECTION
AND ANALYSIS: Risk ratio was used as the summary measure with random effects
model. We assessed heterogeneity between studies using the I2 index. Quality
assessment was done based on Cochrane Handbook Method. MAIN RESULTS: Pooled data
showed no benefit of using cervical pessary in the prevention of preterm births,
birth weights less than 1500 g, less than 2500 g, adverse neonatal events and
fetal/neonatal deaths in twin pregnancies with a short cervix. CONCLUSION: We are
unable to show benefit of using cervical pessary in preventing preterm births in
twin pregnancies with a short cervix. However, as cervical pessary is a
reasonable intervention, there is a need for more randomized controlled trials in
this area.
PMID- 28412852
TI - Transitional hemodynamics in infants of diabetic mothers by targeted neonatal
echocardiography, electrocardiography and peripheral flow study.
AB - OBJECTIVE: Metabolic alterations of intrauterine environment in diabetes mellitus
(DM) lead to fetal cardiac dysfunctions that can persist after birth. The aim of
the study was to assess the cardiovascular adaptation in infants born to diabetic
mothers (IDM) with different degrees of glycometabolic control, in relation to
revised guidelines for diagnosis of DM and quality improvements in neonatal care.
MATERIALS AND METHODS: An observational case-control study was conducted on IDM
with gestational, type 1 and type 2 DM. Relevant maternal and neonatal
anamnestic, clinical and laboratory data were analyzed. Electrocardiographic and
echocardiographic analyses, including structural and systo-diastolic evaluation,
were performed. RESULTS: In 68 IDM enrolled, we observed a lower incidence of
negative perinatal outcome than expected. Comparing to non-IDM, they presented
larger fetal shunts, higher pulmonary pressures, early and atrial wave
velocities. At 72 hours, kinesis and heart rate variability remained low.
Cerebral blood flow velocities were higher. The most serious impairment of
transition was in pregestational IDM. CONCLUSION: Maternal DM impaired neonatal
transitional hemodynamics also in asymptomatic IDM with good glycometabolic
control. These results confirm the need for an early cardiologic and
cerebrovascular evaluation, to identify IDM with delayed maturation at risk of
worse long-term metabolic, cardiovascular, and neurodevelopmental outcome.
PMID- 28412854
TI - Oxidative stress in preeclamptic mother - newborn dyads and its correlation with
early neonatal outcome - a case control study.
AB - BACKGROUND: Preeclamptic mothers are likely to have increased oxidative stress
during pregnancy which can adversely affect the outcome in their neonates.
OBJECTIVES: To measure the oxidative stress in preeclamptic mother- newborn dyads
and correlate it with the immediate neonatal outcome. METHODS: This case control
study conducted in a tertiary care teaching hospital, South India included 71
preeclamptic mothers - newborn dyads (cases) and 72 normal mothers - newborn
dyads (controls). Biochemical parameters including total antioxidant status
(TAS), protein carbonyls and malondialdehyde levels (MDA) were measured in both
maternal and cord blood. Association between these oxidative stress parameters
and early neonatal outcome was studied. RESULTS: All oxidative stress markers
were higher in the preeclampsia group compared to the controls. Cord blood
protein carbonyl levels had significant correlation with maternal levels.
Prematurity, low-birth weight, respiratory distress syndrome (RDS), early onset
sepsis (EOS) and intra-uterine growth restriction (IUGR) were more among cases.
Early neonatal outcomes like death, IUGR, EOS, and RDS had significant
correlation with protein carbonyl levels among the cases. CONCLUSIONS: Oxidative
stress is increased in preeclamptic mother - newborn dyads. Increased protein
carbonyl levels in preeclampsia correlate with adverse early neonatal outcome.
PMID- 28412853
TI - Nitrogen behaviour during thermal drying of mechanically dewatered biosludge from
pulp and paper industry.
AB - An ongoing call to implement a circular economy is underway in the European
Union, and a specific attention has been placed on the forest industry, which
seeks additional recycling routes for its side streams, including biosludge.
Biosludge is often dried and incinerated, thus wasting the nitrogen contained
therein. This paper describes a study in which the release of nitrogen during
thermal drying, the impact of the drying temperatures of 130 degrees C, 180
degrees C, and 210 degrees C on the mass of ammonia released, and the potential
for recovery of nitrogen from biosludge were examined. The results indicate that
1310-1730 mg kgTS-1 of nitrogen was released, which corresponded to 56-74% of the
soluble nitrogen in biosolids or 4.0-5.3% of the total nitrogen. Of this released
nitrogen, 83-85% was identified in condensate and absorbing water, thus
indicating a high potential for recovering nitrogen from biosludge.
PMID- 28412855
TI - Decreased TLR4 expression on monocytes may cause regulatory T cells abnormality
in patients with primary immune thrombocytopenia.
AB - Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune
dysfunctions including T helper type 1 cell (Th1) polarization and regulatory T
cells (Tregs) deficiency. This study aimed to determine the effects of TLR4 on
Treg differentiation and the cytokine production of peripheral blood mononuclear
cells (PBMCs) from patients with ITP. We found that expression of TLR4 on
monocytes was significantly decreased in patients with active ITP than that in
healthy controls and it had positive correlation with platelet count. However,
there was no expression of TLR4 on CD4+ T cells. The result of further
experiments in vitro showed that lipopolysaccharide (LPS) stimulation could
enhance TLR4 expression on monocytes. Additionally, activation of TLR4 with LPS
could promote differentiation of Treg cells and anti-TLR4 attenuated this effect.
There was no significant difference about Th17 cells among three subgroups.
However, the Th17/Treg cell ratio was decreased after stimulation with LPS and
increased with anti-TLR4. Moreover, activation of TLR4 with LPS could
significantly promote the secretion of interleukin-10 (IL-10) and transforming
growth factor-beta1 (TGFB1), while anti-TLR4 significantly suppressed the
secretion of them. Nevertheless, the secretion of IL-17A did not reach the
statistical difference among three subgroups. In summary, decreased TLR4 appears
to cause Tregs abnormality in ITP by modulating Tregs differentiation and
immunoregulatory cytokines.
PMID- 28412856
TI - Investigating the role of IL-33 in the pathogenesis of Behcet's Disease.
AB - OBJECTIVES: Behcet's disease (BD) is an inflammatory disease, characterized by
oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations.
Increased release of several cytokines may play a role in the inflammatory stages
of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role
in inflammation. We analyzed serum IL-33 concentration in BD patients to assess
its possible role in the pathophysiology of this disease. METHODS: The study
included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18
matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked
immunosorbent assay (ELISA). RESULTS: The mean serum IL-33 levels were 4.84 +/-
2.81 pg/ml in the BD patients (6.16 +/- 2.94 pg/ml in the active stage and 2.86
+/- 0.54 pg/ml in the inactive stage) and 2.88 +/- 0.42 pg/ml in the healthy
controls. Serum IL-33 levels were significantly higher in patients with BD
compared with the healthy controls (p < 0.01). In active Behcet patients with
arthritis the mean serum IL-33 level was higher but this finding was not
statistically significant (p = 0.122). CONCLUSION: IL-33 may play a significant
role of in the pathogenesis of BD.
PMID- 28412857
TI - Prevalence of diminished ovarian reserve in Chinese women with polycystic ovary
syndrome and sensitive diagnostic parameters.
AB - OBJECTIVES: To assess the prevalence of diminished ovarian reserve (DOR) in
patients with polycystic ovary syndrome (PCOS) in China, and to search for
sensitive diagnostic parameters. METHODS: Three hundred and thirty eight PCOS
women aged 20-39 years were recruited. Basic characteristics, follicle
stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone
and anti-Mullerian hormone (AMH) were measured. The best indices to diagnose PCOS
with DOR were assessed. RESULTS: The prevalence of DOR in our Chinese PCOS
patients was 16.9%. The level of E2 and FSH and the FSH/LH ratio had a positive
correlation with PCOS and DOR (OR > 1, p < 0.05) independent of age and
testosterone, while AMH and baseline antral follicle count had a negative
correlation (OR < 1, p < 0.05). AMH was a good parameter to diagnose PCOS with
DOR, the cutoff was 2.53 ng/ml, with sensitivity 92.5%, specificity 73.7% and
area under curve 0.932. AMH had a significant positive correlation with LH (r =
0.016, p < 0.05) and testosterone (r = 0.209, p < 0.01), while had significant
negative correlation with age (r=-0.140, p < 0.05), FSH (r=-0.229, p < 0.01) and
FSH/LH ratio (r=-0.240, p < 0.01). CONCLUSIONS: In our study, AMH was a sensitive
parameter to diagnose PCOS with DOR, but to improve the accuracy it will still
need further studies.
PMID- 28412858
TI - Profile of lipophilic antioxidants in the by-products recovered from six
cultivars of sour cherry (Prunus cerasus L.).
AB - The content of tocochromanols and carotenoids in kernels recovered from fruit
pits of six sour cherry (Prunus cerasus L.) cultivars was studied. The highest
concentration was noted for gamma-T (23.50-52.76 mg/100 g dry weight basis (dw)).
Considerably, lower amounts compared to gamma-T were detected for alpha-T, delta
T and alpha-T3 (5.74-13.33, 2.74-4.54 and 0.30-1.16 mg/100 g dw, respectively).
The beta-T and gamma-T3 were quantified only in minor levels. The total amount of
tocochromanols was in the range 41.69-63.48 mg/100 g dw. The levels of total
carotenoids ranged between 0.17 and 0.39 mg/100 dw. The concentration of
tocochromanols and carotenoids in kernels of different sour cherries is cultivar
dependent. A significant correlation (r = 0.985, p < 0.001) has been observed
between the total content of tocochromanols in kernels and scavenging of free
radicals DPPH by native lipophilic antioxidants in the by-products of sour
cherry.
PMID- 28412859
TI - Determination and quantification of carotenoids in sea sponges Raspaciona
aculeata and Dictyonella marsilii present in the Ganzirri Lake (Messina), Italy.
AB - Considering the crucial role of carotenoids exploitable both as nutraceuticals
and also as dyes in food industry, there are many efforts in seeking for new
sources of these pigments, especially in the marine world. In this study, for the
first time, we extracted carotenoids from sea sponges Raspaciona aculeata and
Dictyonella marsilii taken from Ganzirri Lake Messina (Italy). The determination
and quantification of carotenoids was made by UPLC-PDA-MS. Remarkable results
concern renieratene content in R. aculeate found to be over 2570 ppm.
PMID- 28412860
TI - Modeling vascular inflammation and atherogenicity after inhalation of ambient
levels of ozone: exploratory lessons from transcriptomics.
AB - BACKGROUND: Epidemiologic studies have linked inhalation of air pollutants such
as ozone to cardiovascular mortality. Human exposure studies have shown that
inhalation of ambient levels of ozone causes airway and systemic inflammation and
an imbalance in sympathetic/parasympathetic tone. METHODS: To explore molecular
mechanisms through which ozone inhalation contributes to cardiovascular
mortality, we compared transcriptomics data previously obtained from
bronchoalveolar lavage (BAL) cells obtained from healthy subjects after
inhalational exposure to ozone (200 ppb for 4 h) to those of various cell samples
from 11 published studies of patients with atherosclerotic disease using the
Nextbio genomic data platform. Overlapping gene ontologies that may be involved
in the transition from pulmonary to systemic vascular inflammation after ozone
inhalation were explored. Local and systemic enzymatic activity of an overlapping
upregulated gene, matrix metalloproteinase-9 (MMP-9), was measured by zymography
after ozone exposure. RESULTS: A set of differentially expressed genes involved
in response to stimulus, stress, and wounding were in common between the ozone
and most of the atherosclerosis studies. Many of these genes contribute to
biological processes such as cholesterol metabolism dysfunction, increased
monocyte adherence, endothelial cell lesions, and matrix remodeling, and to
diseases such as heart failure, ischemia, and atherosclerotic occlusive disease.
Inhalation of ozone increased MMP-9 enzymatic activity in both BAL fluid and
serum. CONCLUSIONS: Comparison of transcriptomics between BAL cells after ozone
exposure and various cell types from patients with atherosclerotic disease
reveals commonly regulated processes and potential mechanisms by which ozone
inhalation may contribute to progression of pre-existent atherosclerotic lesions.
PMID- 28412861
TI - The association between progestins, nuclear receptors expression and inflammation
in endometrial stromal cells from women with endometriosis.
AB - Endometriosis is an inflammatory disease and nuclear receptors play a crucial
role in mediating the inflammatory response. In endometrial stromal cells (ESC),
nuclear receptors expression can be influenced by the local environment.
Progestins are first-line, on-label treatments of endometriosis that may have
direct effects on endometriotic lesions through these nuclear receptors.
Therefore, we investigated whether there was an association between nuclear
receptors expression and the influence of progestins on inflammatory cytokines
production in a preliminary, in vitro study with primary cultures. ESC from
endometrial biopsies of six subjects with histologically confirmed endometriosis
were treated for 6 h with medium alone or with TNF-alpha (10 or 100 ng/ml) in the
presence of dienogest (DNG), medroxyprogesterone acetate (MPA) and norethisterone
acetate (NETA) 10-5 M. The progestin-mediated change in IL6, IL8 and MCP-1 mRNA
transcription was measured, as was the PRA, PRB, GR, AR and MCR protein
expression. The change (medium versus TNF-alpha 10 ng/ml and medium versus TNF
alpha 100 ng/ml) in IL6 mRNA transcription was positively associated with the
change in PRB, but not PRA with both DNG and NETA treatment. The change in IL8
mRNA was negatively associated with AR expression in the presence of NETA. The
change in MCP-1 mRNA expression was positively associated with GR expression and
negatively associated with MCR after MPA treatment. The associations between the
change in cytokines mRNA expression and nuclear receptors protein expression in
response to progestins activity may indirectly suggest different activities of
these compounds at a local level worthy of further investigations.
PMID- 28412863
TI - Oxidized lipoprotein lipids and atherosclerosis.
AB - Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP),
which are known to impair normal physiological functions and stimulate
atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are
active carriers of LOP, low-density lipoprotein (LDL) directing transport toward
peripheral tissues, and high-density lipoprotein (HDL) being active in the
reverse transport. It has been proposed that the lipoprotein-specific transport
of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This
article gives an overview of the present knowledge of lipoprotein LOP transport
and its association with the risk of atherosclerosis and cardiovascular diseases
(CVD). Evidence of the significance of lipoprotein LOP transport comes mainly
from studies of physiological oxidative stress and is supported by studies of the
functionality apolipoprotein A-1 mimetic peptides. A large body of data has
accumulated indicating that lipoprotein LOP transport is connected to the risk of
atherosclerosis. While high levels of LOP carried by LDL are indicative of
elevated risk, high LOP level in HDL appears to associate with protection. If
confirmed, the proposed lipoprotein LOP transport function would affect
conception of the etiology of atherosclerosis, but would not conflict current
views of the pathophysiological mechanisms. It could open new perspectives, such
as the dietary origin of LOP, and the protective function of HDL in clearance of
LOP. Focusing on LOP could give additional tools especially for prevention and
diagnosis, but would not radically change the management of atherosclerosis and
CVD.
PMID- 28412862
TI - Impact of transvaginal hydrolaparoscopy ovarian drilling on ovarian stromal blood
flow and ovarian volume in clomiphene citrate-resistant PCOS patients: a case
control study.
AB - Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in
gynecology. In PCOS patients vascularization parameters are altered. Transvaginal
hydrolaparoscopy (THL) is a mini-invasive approach for ovarian drilling in PCOS
patients. In this study, we assessed the effect of ovarian drilling using THL on
ovarian volume (OV) and vascularization index (VI) using 3D power Doppler
ultrasonography in CC-resistant PCOS patients. A case-control study on 123 CC
resistant PCOS women who underwent THL ovarian drilling was performed. Patients
underwent 3D ultrasound and power Doppler to measure VI, flow index (FI),
vascularization flow index (VFI) and to evaluate OV before and after the
procedure, at six months, and on the early follicular phase of the menstrual
cycle. After THL ovarian drilling, OV and power Doppler flow indices were
significantly reduced compared to pre-operative values (OV: 7.85 versus 11.72
cm3, p < 0.01; VI: 2.50 versus 4.81, p < 0.01; VFI: 1.10 versus 2.16, p < 0.01;
FI: 32.05 versus 35.37, p < 0.01). In conclusion, THL ovarian drilling seems to
reduce OV and 3D power Doppler indices, and could therefore be a viable
alternative to LOD in PCOS patients resistant to medical therapy.
PMID- 28412864
TI - Cutaneous allergic drug reactions: update on pathophysiology, diagnostic
procedures and differential diagnosic.
AB - Important changes in the understanding and management of drug hypersensitivity
reactions during the last years result from the increasing importance of
biologics in medical practice, which differ in their spectrum of adverse drug
reactions (ADRs) from the classical covalent drugs. With regard to covalent
drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing
role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause
of anaphylactic and photosensitivity reactions. Especially in allergic reactions
to NSAIDs, pseudoallergic reactions should be considered in the differential
diagnosis. In opposite to the main cutaneous allergic drug reactions such as
urticaria or maculopapular skin rash, in which antibiotics are the main culprits,
in severe drug allergic reactions such as SJS (Stevens-Johnson Syndrome), TEN
(Toxic Epidermal Necrolysis), or DRESS (Drug Reaction with Eosinophilia and
Systemic Symptoms) Syndrome, compounds like allopurinol and anticonvulsants are
the main causes. Similar mutations in the IL36R gene, which were found in both
patients with an AGEP (Acute Generalized Exanthematous Pustulosis) and pustular
psoriasis, make the differential diagnosis more difficult and raise the question
whether there is a difference between these diseases or whether AGEP is not just
a drug induced pustular psoriasis. Finally, some special aspects of side effects
of biologics and targeted therapies respectively are discussed.
PMID- 28412865
TI - Strength adaptation to squat exercise is different between Caucasian and South
Asian novice exercisers.
AB - This study compared the progression of muscular strength (MS) adaptation between
age-matched Caucasian (CAUC) and South Asian (SOU) men during 6 weeks (3* week-1)
of resistance training. MS was determined pre and post intervention by 3
repetition maximum (3RM) strength tests, and data were analysed using repeated
measures ANOVA. Pre-intervention upper and lower body 3RM were similar between
groups and both upper and lower body 3RM increased in CAUCs (P < .001) and SOUs
(P < .001) following resistance training. However, lower body strength adaptation
(3RM) was higher in CAUCs compared with SOUs (P = .002). There was a significant
group * time interaction in strength progression of the squat exercise (P = 0.03)
from session 7 through to 18 (completion). The present study offers novel but
provisional data that lower body strength adaptation is slower in SOU than CAUC
men despite comparable adaptation to upper body strength.
PMID- 28412866
TI - Comparison of the morphokinetic parameters of embryos according to ovarian
reserve in IVF cycles.
AB - The aim of this study is to evaluate the impact of ovarian reserve and age of
women on early morphokinetic parameters of embryos with a time-lapse monitoring
system. In total, 197 infertile couples with poor ovarian reserve (Group 1, n =
41), normal ovarian reserve (Group 2, n = 59), or polycystic ovaries (Group 3, n
= 97) were included. The time from insemination to the following events were
analyzed: pronuclear fading (Pnf) and cleavage to 2, 3, 4 and 5 cells. The
optimal ranges for morphokinetic parameters of t5, s2 and cc2 in each group were
also evaluated. In total, 1144 embryos were evaluated. Morphokinetic parameters
did not differ statistically between the groups. Data were analyzed according to
different age groups (20-30, 30-40, >40). The morphokinetic parameters did not
differ statistically in Group 1 and 3. In Group 2, the times from insemination to
tPnf, t2, t3, t4 were significantly shorter in the younger age group than the
older age group (p < 0.05). The percentages of optimal embryos, according to t5,
s2 and cc2, did not differ statistically between the groups. In conclusion,
ovarian reserve did not seem to affect the morphokinetic parameters of embryos.
PMID- 28412867
TI - Weight gain, body image and sexual function in young patients treated with
contraceptive vaginal ring. A prospective pilot study.
AB - INTRODUCTION: Oral contraceptives could induce mood changes. As far as our
knowledge, there are no studies in literature that have examined the role of
vaginal contraception in self-perceived body image. AIM: To evaluate the effects
of intravaginal contraception on weight gain and perceived body image in relation
with the Beck's Depression Inventory questionnaire (BDI) and the McCoy Female
Sexuality Questionnaire (MFSQ). METHODS: Twenty-one adult (18-35 years old)
eumenorrheic (menstrual cycle of 25-35 days), lean (body mass index - BMI - of 19
25 kg/m2) women who were referred for hormonal contraception were administered
the Stunkard Figure Rating Scale (FRS), BDI and MFSQ. Subjects were studied in
basal condition and after 6 months of therapy with vaginal contraception
(NuvaRing(r); Organon-Schering-Plough Italia, Milan, Italy). MAIN OUTCOME
MEASURES: BMI, FRS, MFSQ and BDI. RESULTS: After 6 months of therapy with
NuvaRing(r), both body weight (60.0 +/- 8.3; p = 0.050) and BMI (22.1 +/- 3.1; p
= 0.028) slightly, but statistically, increased. FRS and BDI showed no
differences after the vaginal contraception. Hormonal contraception was
associated with a significant decrease in the two-factor Italian MFSQ score.
CONCLUSIONS: Vaginal ring seems a good alternative to other hormonal
contraceptive not significantly altering the female sexuality and not influencing
the FRS and BDI.
PMID- 28412868
TI - Prevalence of pre-high blood pressure and high blood pressure among non
overweight children and adolescents using international blood pressure references
in developed regions in China.
AB - BACKGROUND: There is a lack of data on the prevalence of pre-high blood pressure
(PreHBP) and high blood pressure (HBP), based on recent international blood
pressure references, in non-overweight children and adolescents. AIM: To describe
the prevalence of PreHBP and HBP in non-overweight children and adolescents in
developed regions of China. SUBJECTS AND METHODS: In total, 588 097 non
overweight children and adolescents aged 6-17 years from the National Surveys on
Chinese Students' Constitution and Health in 2015 were included. RESULTS: The
prevalence of PreHBP was 13.41% and subjects in urban areas had a higher
prevalence of PreHBP (14.14%) than those in rural areas (12.92%). Subjects in
regions with a high (13.56%) or moderate (13.61%) socioeconomic status showed a
higher prevalence of PreHBP than those in regions with a relatively low
socioeconomic status (12.76%). A similar pattern was found for the prevalence of
HBP, and the prevalence of HBP was 18.25% for all participants, 20.55% for
subjects in urban areas, 16.71% in rural areas, 18.76% in high socioeconomic
areas, 18.62% in moderate socioeconomic areas and 16.70% in relatively low
socioeconomic areas. CONCLUSION: A large proportion of non-overweight children
and adolescents had elevated blood pressure and there were urban-rural and
socioeconomic disparities in the prevalence of elevated blood pressure.
PMID- 28412869
TI - A novel Salvialactomine from the callus culture of Salvia santolinifolia Boiss.
AB - A novel compound Salvialactomine (1) along with two other unusual occurring
natural products Pentatriacontanoic acid 1, 3-dihydroxypropyl ester (2) and 5
Methylflavone (3) were isolated from the callus of Salvia santolinifolia Boiss.
Callus was initiated on MS medium containing NAA (0.5 mg/L) and further sub
cultured on MS medium supplemented with NAA with BA (0.5 + 1.5 mg/L). The
structures of isolated compounds were determined by using mass spectrometry, 1D,
and 2D-NMR techniques. Compounds 1, and 3 were tested for two different cancer
cell lines, i.e. Hela (Cervical cancer cell) and PC-3 (Prostate cancer cells).
IC50 was found as > 30 using Doxorobicin (0.912 +/- 0.12 MUmol L-1) as a
standard.
PMID- 28412871
TI - The effect of oil and water-soluble contrast medium in hysterosalpingography on
thyroid function.
AB - Hysterosalpingography (HSG) using iodinated contrast medium is X-ray diagnostic
test that examines the inside of the uterus and fallopian tubes in infertile
women. In this study, we compared thyroid function (thyroid stimulating hormone:
TSH and free-T4: FT4 levels) after HSG with an oil-soluble contrast medium (OSCM)
and a water-soluble contrast medium (WSCM). One hundred and sixty-four and 94
patients with normal thyroid function received HSG with OSCM and WSCM,
respectively. Approximately 25% of the women in the OSCM group developed
subclinical hypothyroidism (SCH), whereas only less than 10% of the patients in
the WSCM group developed SCH. Our data clearly indicate that WSCM is safe for
thyroid function in women who plan to get pregnant.
PMID- 28412870
TI - The effect of diabetes on ovaries in a rat model: the role of interleukin-33 and
apoptosis.
AB - Interleukin-33 (IL-33) is a novel cytokine involved in diabetes mellitus (DM) but
its role in diabetic ovarian injury is unknown. As IL-33 is modulated by
apoptosis, we aimed at investigating the effect of diabetes on ovaries in terms
of evaluating apoptosis and IL-33 in a rat model. In this prospective
experimental study, 16 female, nonpregnant Sprague-Dawley albino rats (12 weeks,
220-240 g) were randomly divided into two groups. Group 1 included eight healthy
nondiabetic rats as controls and group 2 included eight rats in which diabetes
was induced by intraperitoneal (i.p) injection of streptozotocin (STZ). After
overt DM occurred (blood glucose >400 mgr/dl), all animals were euthanized and
blood samples were collected by cardiac puncture for biochemical analysis.
Bilateral oophorectomy was performed for histopathological examination. Serum
levels of IL-33 and ovarian IL-33 and caspase-3 immunoexpressions were assessed.
Immunoexpressions of caspase-3 and IL-33 were significantly higher in ovarian
stromal cells of the diabetic rats compared to the controls. Also, in diabetic
group, serum IL33 levels were significantly higher than the control group. In
conclusion, increased IL-33 was observed both in serum and ovaries of STZ-induced
diabetic rats as well as increased apoptosis in these diabetic rats. IL-33 may
contribute to the apoptosis in diabetic ovarian injury.
PMID- 28412872
TI - Chinese Xibe population genetic composition according to linkage groups of X
chromosomal STRs: population genetic variability and interpopulation comparisons.
AB - BACKGROUND: The Xibe population is one of China's officially recognised
populations and is now distributed separately from west to east in the northern
part of China. X-chromosomal short tandem repeats have a special inheritance
pattern, and could be used as complements in forensic application, especially for
complex or deficiency cases. SUBJECTS AND METHODS: This study obtained the
allelic and haplotypic frequencies of 19 X-STR loci in the Xibe population from
Xinjiang Uygur Autonomous Region, China, and studied the genetic differentiations
between the Xibe and other populations. RESULTS: The combined power of
discrimination in females and males and mean exclusion chances in deficiency
cases, normal trios and duo cases was at least 0.999 999 994. In the haplotypic
study, the Xibe population showed a more similar pattern of haplotype
distribution with Asian populations than populations from other continents, while
allelic study also indicated a closer relationship between the Xibe and Asian
populations. CONCLUSIONS: The 19 X-STR loci would be useful in forensic
application in the studied population. The Xibe population showed a closer
genetic relationship with Asian populations in the study, and more population
data would be necessary for more detailed genetic relationship studies.
PMID- 28412873
TI - beta3-Adrenergic receptors, adipokines and neuroendocrine activation during
stress induced by repeated immune challenge in male and female rats.
AB - The main hypothesis of the study is that stress associated with repeated immune
challenge has an impact on beta3-adrenergic receptor gene expression in the
brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses
of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was
associated with body weight loss and increased anxiety-like behavior. In LPS
treated animals of both sexes, beta3-receptor gene expression was increased in
the prefrontal cortex but not the hippocampus. LPS treatment decreased beta3
receptor gene expression in white adipose tissue with higher values in males
compared to females. In the adipose tissue, LPS reduced peroxisome proliferator
activated receptor-gamma, leptin and adiponectin gene expression, but increased
interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted
in increased concentrations of plasma aldosterone and corticosterone with higher
values of corticosterone in females compared to males. Concentrations of
dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels
in the frontal cortex were lower in the LPS-treated animals compared to the
controls. Thus, changes of DHEA levels in the brain take place irrespective of
the changes of this neurosteroid in plasma. We have provided the first evidence
on stress-induced increase in beta3-adrenergic receptor gene expression in the
brain. Greater reduction of beta3-adrenergic receptor expression in the adipose
tissue and of the body weight gain by repeated immune challenge in male than in
female rats suggests sex differences in the role of beta3-adrenergic receptors in
the metabolic functions. LPS-induced changes in adipose tissue regulatory factors
and hormone concentrations might be important for coping with chronic infections.
PMID- 28412874
TI - Effects of Regulatory Support Services on Institutional Review Board Turnaround
Times.
AB - We evaluated how regulatory support services provided by University of Illinois
at Chicago's Center for Clinical and Translational Science may reduce
Institutional Review Board (IRB) turnaround times. IRB applications were
categorized by receipt of any regulatory support and amount of support received.
Turnaround time included total turnaround time, time for IRB review, and time for
investigators to modify protocols. There were no differences in any turnaround
times for supported versus nonsupported applications. However, for supported
applications, those receiving more intensive support had total turnaround times
16.0 days ( SE 7.62, p < .05) faster than those receiving less intensive support.
Receiving higher regulatory support may be associated with faster approval of IRB
submissions.
PMID- 28412875
TI - Amino acid and acylcarnitine profiles in perinatal asphyxia: a case-control
study.
AB - OBJECTIVE: To estimate cord blood amino acid and acylcarnitine levels in term
newborns exposed to perinatal asphyxia. MATERIALS AND METHODS: We studied 45
asphyxiated term newborns (cases) and 20 gestational age-matched healthy newborns
(control). 16 cases developed HIE according to clinical scoring and amplitude
integrated electroencephalography. Asphyxiated cases were accordingly subdivided
into: HIE group (n = 16) and Asphyxia group (n = 29). Amino acid and
acylcarnitine levels were measured in cord blood dried spot samples from all
newborns using ultra-performance liquid chromatography-mass spectrometry (UPLC
MS). Data were analyzed using one-way ANOVA with post hoc test and MetaboAnalyst
2. RESULTS: Distinct metabolite alterations were detected in cases versus
control, in HIE versus Asphyxia, and in Survivors within HIE group (n = 6) versus
nonsurvivors (n = 10). Principal component analysis (PCA) and partial least
squares-discriminate analysis (PLS-DA) showed increased levels of methionine and
certain acylcarnitines, but reduced levels of ornithine, histidine, and arginine.
Metabolite set enrichment analysis (MSEA); compared to KEGG library metabolite
sets, identified some disorders with similar metabolomic derangements.
CONCLUSIONS: We report UPLC-MS detectable alterations of amino acids and
acylcarnitines in asphyxiated newborns at birth, that can serve as early
diagnostic bedside biomarkers for HIE and predictors for its short-term outcome,
and in the near future, as therapeutic targets.
PMID- 28412876
TI - Effect of breastfeeding on postpartum depressive symptoms among adolescent and
young adult mothers.
AB - PURPOSE: To describe the association between breastfeeding and postpartum
depressive symptoms among a sample of adolescent and young adult mothers and to
determine whether breastfeeding difficulty moderates this association. MATERIALS
AND METHODS: Data were derived from a prospective cohort of pregnant adolescent
and young adult females (ages 14-21) as they transitioned to parenthood. This
analysis uses data collected during pregnancy and at 6 months postpartum among
mothers (n = 137) who initiated breastfeeding. Multivariable linear regression
was used to adjust for prenatal depressive symptoms and other potential
confounders. RESULTS: Postpartum depressive symptoms were not significantly
associated with breastfeeding duration or breastfeeding at 6 months. Early
breastfeeding difficulty moderated the association between depressive symptoms
and breastfeeding at 6 months. Among young mothers who were still breastfeeding
at 6 months, those who reported no early breastfeeding difficulties had the
lowest depressive scores and those who reported much early breastfeeding
difficulty had the highest depressive scores at 6 months. CONCLUSIONS: Minimizing
challenges with breastfeeding may help improve postpartum mental health among
adolescent and young adult mothers. Health care providers should help young
pregnant women manage expectations about breastfeeding and ensure that they are
linked to appropriate professional breastfeeding support during the early
postpartum period.
PMID- 28412877
TI - Retrospective Time Perception in Korsakoff's Syndrome.
AB - The authors investigated retrospective timing in participants with Korsakoff's
syndrome. Patients were assessed on four retrospective tasks on which they were
instructed to read three-digit numbers aloud (15 seconds), fill connected squares
(30 seconds), decide whether words were abstract or concrete (45 seconds), or
read aloud a text about mushroom picking (60 seconds). Participants were not
aware of the task's timing until the end of the tasks, when they were asked to
estimate the elapsed time. Results revealed an underestimation of the elapsed
time in Korsakoff participants, suggesting that time is perceived to pass quickly
for these participants.
PMID- 28412878
TI - "Top-Down" Mu-Opioid System Function in Humans: Mu-Opioid Receptors in
Ventrolateral Prefrontal Cortex Mediate the Relationship Between Hedonic Tone and
Executive Function in Major Depressive Disorder.
AB - Cognitive dysfunction and anhedonia, the reduced ability to experience pleasure,
are commonly comorbid symptoms that are persistent following successful
resolution of negative affect in major depressive disorder (MDD). Little is known
about whether they share common etiology. In the present study, the relationship
between ventrolateral prefrontal cortex (VLPFC) activity, cognitive dysfunction
(i.e., executive dysfunction), and positive emotionality was investigated in
conjunction with mu-opioid neurotransmission in a sample of 39 MDD patients.
Results suggest that increased endogenous mu-opioid tone in the VLPFC mediates
the relationship between increased trait positive emotionality and more efficient
executive functioning.
PMID- 28412879
TI - Quantitative Analysis of Transnasal Anterior Skull Base Approach: Report of
Technology for Intraoperative Assessment of Instrument Motion.
AB - OBJECTIVE: To develop a method to measure intraoperative surgical instrument
motion. This model will be applicable to the study of surgical instrument
kinematics including surgical training, skill verification, and the development
of surgical warning systems that detect aberrant instrument motion that may
result in patient injury. DESIGN: We developed an algorithm to automate
derivation of surgical instrument kinematics in an endoscopic endonasal skull
base surgery model. Surgical instrument motion was recorded during a cadaveric
endoscopic transnasal approach to the pituitary using a navigation system
modified to record intraoperative time-stamped Euclidian coordinates and Euler
angles. Microdebrider tip coordinates and angles were referenced to the cadaver's
preoperative computed tomography scan allowing us to assess surgical instrument
kinematics over time. A representative cadaveric endoscopic endonasal approach to
the pituitary was performed to demonstrate feasibility of our algorithm for
deriving surgical instrument kinematics. CONCLUSIONS: Technical feasibility of
automatically measuring intraoperative surgical instrument motion and deriving
kinematics measurements was demonstrated using standard navigation equipment.
PMID- 28412880
TI - Comment Concerning Cherkasova et al. (2016), Efficacy of Cognitive Behavioral
Therapy with and without Medication for Adults with ADHD.
PMID- 28412882
TI - Effects of a behaviour management technique for nursing staff on behavioural
problems after acquired brain injury.
AB - The ABC method is a behaviour management technique for use by nurses. ABC refers
to the identification of Antecedent events, target Behaviours, and Consequent
events. In this longitudinal intervention study with double baseline measurements
we evaluated the effectiveness of the ABC method in patients with behavioural
problems after acquired brain injury. Fifty-six patients participated in this
study. Outcome was measured in terms of overall neuropsychiatric problem
behaviour, aggression, apathy and emotional burden experienced by nurses. A
process evaluation was performed to investigate usability and acceptability of
the method and identify factors that influenced effectiveness. Friedman's ANOVA
showed a small significant reduction over time in overall neuropsychiatric
problem behaviour and aggression. The reduction was most prominent between the
first baseline measurement and the post-implementation and follow-up
measurements, not between the second baseline measurement and the post
implementation or follow-up measurements. This first group study on the effects
of the ABC method could not prove this technique is effective for patients with
behavioural problems after acquired brain injury. Nurses indicated that the ABC
method was not fully implemented in their daily routines. This may have
influenced results and makes it yet premature to draw firm conclusions on the
effects of the ABC method.
PMID- 28412881
TI - Glutathione S-transferase A1 (GSTA1) as a marker of acetaminophen-induced
hepatocyte injury in vitro.
AB - Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers
are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1
(GSTA1) plays a significant role in the metabolism of APAP. Primary mouse
hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced
hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and
determine whether GSTA1 could be a prognostic marker in vitro. A significant
increase (p < .05) in GSTA1 in cell culture supernatant was detected at 6 h after
APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase
(AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
showed marked differences (p < .05) at 8 h after APAP exposure, 2 h later than
GSTA1. Furthermore, GSTA1 increased in a dose-dependent manner with APAP
treatment. GSTA1 increased significantly (p < .05) at a concentration of 5.0
mmol/L APAP, while the marked changes in ALT, AST and other indexes were
undetectable until the concentration of APAP reached 7.5 mmol/L. These results
suggest that increased GSTA1 can be more sensitive than ALT and other indexes as
a marker of APAP-induced hepatic injury, which provide novel diagnostic index for
APAP-induced hepatic injury and supply valuable information to further understand
the pathogenesis of liver damage.
PMID- 28412883
TI - Polyphenols of virgin coconut oil prevent pro-oxidant mediated cell death.
AB - Virgin coconut oil (VCO), extracted from the fresh coconut kernel, is a food
supplement enriched with medium chain saturated fatty acids and polyphenolic
antioxidants. It is reported to have several health benefits including lipid
lowering, antioxidant and anti-inflammatory activities. The pharmacological
benefits of VCO have been attributed to its polyphenol content (VCOP), the
mechanistic basis of which is less explored. Liquid chromatography/mass
spectroscopy (LC/MS) analysis of VCOP documented the presence of gallic acid,
ferulic acid (FA), quercetin, methyl catechin, dihydrokaempferol and myricetin
glycoside. Pre-treatment of VCOP at different concentrations (25-100 MUg/mL)
significantly reduced the H2O2 and 2,2'-azobis (2-amidinopropane) dihydrochloride
(AAPH) induced cell death in HCT-15 cells. Giving further insight to its
mechanistic basis, oxidative stress induced alterations in glutathione (GSH)
levels and activities of GR (Glutathione-Reductase), GPx (Glutathione
Peroxidase), GST (Glutathione-S-Transferase) and catalase (CAT) were restored to
near-normal by VCOP, concomitantly reducing lipid peroxidation. The efficacy of
VCOP was similar to that of Trolox and FA added in culture. The study thus
suggests that VCOP protects cells from pro-oxidant insults by modulating cellular
antioxidant status.
PMID- 28412884
TI - Horizontally rotating disc recirculated photoreactor with TiO2-P25 nanoparticles
immobilized onto a HDPE plate for photocatalytic removal of p-nitrophenol.
AB - In this study, a horizontally rotating disc recirculated (HRDR) photoreactor
equipped with two UV lamps (6 W) was designed and fabricated for photocatalytic
removal of p-nitrophenol (PNP). Photocatalyst (TiO2) nanoparticles were
immobilized onto a high-density polyethylene (HDPE) disc, and PNP containing
solution was allowed to flow (flow rate of 310 mL min-1) in radial direction
along the surface of the rotating disc illuminated with UV light. The efficiency
of direct photolysis and photocatalysis and the effect of rotating speed on the
removal of PNP were studied in the HRDR photoreactor. It was found that TiO2-P25
nanoparticles are needed for the effective removal of PNP and there was an
optimum rotating speed (450 rpm) for the efficient performance of the HRDR
photoreactor. Then effects of operational variables on the removal efficiency
were optimized using response surface methodology. The results showed that the
predicted values of removal efficiency are consistent with experimental results
with an R2 of 0.9656. Optimization results showed that maximum removal percent
(82.6%) was achieved in the HRDR photoreactor at the optimum operational
conditions. Finally, the reusability of the HRDR photoreactor was evaluated and
the results showed high reusability and stability without any significant
decrease in the photocatalytic removal efficiency.
PMID- 28412885
TI - Antenatal taurine supplementation in fetal rats with growth restriction improves
neural stem cell proliferation by inhibiting the activities of Rho family
factors.
AB - OBJECTIVE: To investigate whether antenatal taurine supplementation improves
neural stem cell proliferation in rats with fetal growth restriction (FGR)
through regulating the activity of Rho family factors. METHODS: FGR models were
established via food restriction throughout pregnancy. Pregnant rats were
randomly divided into the control group, the FGR group (given 40% of the normal
daily feeding in the control group), and the Taurine group (FGR model treated
with 300 mg/kg.d taurine from gestational day seven). Expression of fatty acid
binding protein-7 (FABP-7), Rho-associated coiled coil-forming protein kinase
(ROCK2), Ras homolog gene family member A (RhoA), and rac in the brains of
newborn rats was detected by reverse transcription-polymerase chain reaction (RT
PCR), immunohistochemistry (IHC), and Western blotting (WB). RESULTS: Relative
FABP7 mRNA levels, the optical density (OD) values of FABP7-positive cells and
the expression levels of the tested proteins all demonstrated that the number of
neural stem cells (NSCs) in brain tissue was lower in the FGR group than in the
control group but was significantly increased after antenatal taurine
supplementation (p < .05). Compared with the control group, the mRNA and protein
levels of RhoA and ROCK2 were higher in the FGR group but lower in the Taurine
group (p < .05). In contrast, the rac mRNA level was lower in the FGR group than
in the control group but was higher in the Taurine group (p < .05). CONCLUSIONS:
Taurine prenatal supplementation improved neural stem cell proliferation in rats
with FGR by inhibiting the activity of Rho family factors.
PMID- 28412886
TI - A Long-Term, Open-Label, Safety Study of Triple-Bead Mixed Amphetamine Salts
(SHP465) in Adults With ADHD.
AB - OBJECTIVE: The aim of this study was to evaluate the long-term safety of triple
bead mixed amphetamine salts (MAS) in adults with ADHD. METHOD: Adults meeting
Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV
TR) ADHD criteria and satisfying study criteria from one of two antecedent
studies were enrolled in this 52-week (dose titration, 4 weeks; dose maintenance,
11 months) open-label extension. The protocol included 12.5- to 75-mg triple-bead
MAS but was amended to a maximum of 50-mg triple-bead MAS. Safety evaluations
included treatment-emergent adverse events (TEAEs) and vital signs. Clinical
outcome measures included ADHD Rating Scale-IV (ADHD-RS-IV) total score changes.
RESULTS: Of 505 enrolled participants, 266 completed the study; the M +/- SD
daily dose during the study was 48.0 +/- 15.96 mg. The most frequent TEAEs were
insomnia (initial insomnia, insomnia, early morning awakening, middle insomnia;
38.2%), headache (25.7%), and dry mouth (20.2%). Study discontinuations were more
frequent with higher doses of triple-bead MAS (37.5-75 mg) than with lower doses
(12.5 and 25 mg). Blood pressure and pulse increases were observed at end-of
study. Mean ADHD-RS-IV total score decreases from antecedent study and open-label
baselines at end-of-study were -23.3 +/- 11.44 and -7.9 +/- 13.19, respectively.
CONCLUSION: Triple-bead MAS exhibited a long-term safety profile comparable with
previous reports and demonstrated evidence of continued symptom control for up to
12 months.
PMID- 28412887
TI - Preventing and De-escalating Aggressive Behavior Among Adult Psychiatric
Patients: A Systematic Review of the Evidence.
AB - OBJECTIVE: The project goal was to compare the effectiveness of strategies to
prevent and de-escalate aggressive behaviors among psychiatric patients in acute
care settings, including interventions for reducing use of seclusion and
restraint. METHODS: Relevant databases were systematically reviewed for
comparative studies of violence prevention and de-escalation strategies involving
adult psychiatric patients in acute care settings. Studies (trials and cohort
studies) were required to report on aggression or seclusion or restraint
outcomes. Both risk of bias, an indicator of quality of individual studies, and
strength of evidence (SOE) for each outcome were independently assessed by two
study personnel. RESULTS: Seventeen primary studies met inclusion criteria.
Evidence was limited for benefits and harms; information about characteristics
that might modify the interventions' effectiveness, such as race or ethnicity,
was especially limited. All but one study had a medium or high risk of bias and
thus presented worrisome limitations. For prevention, risk assessment reduced
both aggression and use of seclusion and restraint (low SOE), and multimodal
interventions reduced the use of seclusion and restraint (low SOE). SOE for all
other interventions, whether aimed at preventing or de-escalating aggression, and
for modifying characteristics was insufficient. CONCLUSIONS: Available evidence
about strategies for preventing and de-escalating aggressive behavior among
psychiatric patients is very limited. Two preventive strategies, risk assessment
and multimodal interventions consistent with the Six Core Strategies principles,
may effectively lower aggressive behavior and use of seclusion and restraint, but
more research is needed on how best to prevent and de-escalate aggressive
behavior in acute care settings.
PMID- 28412888
TI - Postdeployment Behavioral Health Screens and Linkage to the Veterans Health
Administration for Army Reserve Component Members.
AB - OBJECTIVE: Approximately three to six months after returning from deployment,
military service members complete the Post-Deployment Health Reassessment
(PDHRA), which includes screens for alcohol misuse, depression, and posttraumatic
stress disorder (PTSD). To determine whether Army Reserve Component (RC) members
(Army National Guard and Army Reserve) with positive screening scores on the
PDHRA receive needed care, the investigators examined the association between
positive scores and enrollment and utilization of care ("linkage") in the
Veterans Health Administration (VHA), as well as rescreening scores, diagnosis,
and behavioral treatment in VHA. METHODS: Mixed-effects regression models were
used to predict linkage to VHA within six months after RC members (N=73,164)
completed the PDHRA, with alcohol misuse, depression, and PTSD screen scores as
key independent variables. Regression models were stratified by gender and
National Guard versus Reserve status. Among those who linked to VHA (N=25,168),
screening scores and subsequent diagnosis and treatment in VHA were also
examined. RESULTS: Army RC members with positive PTSD and depression screening
scores were more likely than those with negative screens to link to VHA, and most
(54%-84%) received VHA treatment once diagnosed. Positive screens for alcohol
misuse were associated with linkage to VHA for men but not for women, and
treatment rates for alcohol use disorders were relatively low (0%-25%) for both
men and women diagnosed as having an alcohol use disorder. CONCLUSIONS: The
finding that Army RC members with greater indications of behavioral health
problems linked to VHA is encouraging. However, more outreach and treatment
engagement strategies could be directed to those with alcohol use disorder,
particularly women.
PMID- 28412889
TI - Diabetes Prevalence Among Racial-Ethnic Minority Group Members With Severe Mental
Illness Taking Antipsychotics: Double Jeopardy?
AB - OBJECTIVE: This study assessed differences in diabetes prevalence based on race
ethnicity among people with severe mental illnesses. METHODS: This retrospective
cohort study examined diabetes prevalence in 2009 among California Medicaid
enrollees with severe mental illness who were screened for diabetes (N=19,364).
Poisson regression assessed differences in diabetes prevalence by race-ethnicity.
The sample was standardized to the U.S. POPULATION: RESULTS: The overall
prevalence of diabetes was 32.0%. The adjusted prevalence for all minority groups
with severe mental illness, except for Asians, was significantly higher than for
whites (1.21-1.28 adjusted prevalence ratios). With inverse probability weighting
to reduce selection bias captured by measured factors, estimated prevalence of
diabetes among screened participants was 27.3%. CONCLUSIONS: The prevalence of
diabetes in minority groups with severe mental illness was significantly higher
than among whites with severe mental illness. Mental health administrators should
implement universal diabetes screening with specific outreach efforts targeting
minority populations with severe mental illness.
PMID- 28412890
TI - Three Problems With Current Digital Mental Health Research . . . and Three Things
We Can Do About Them.
AB - An increasingly large body of randomized controlled trials has demonstrated the
efficacy of mental health technologies, such as Web-based and mobile
interventions, to prevent and treat mental disorders and increase psychological
well-being. However, there is little evidence that these tools can be
successfully implemented in clinical settings. The authors highlight three widely
held misconceptions that they believe are holding back the field, and they
reconceptualize the issues to strengthen the path toward implementation and
accelerate innovation.
PMID- 28412891
TI - Service Receipt and Mental Disorders in Child Welfare and Mental Health Systems
in Los Angeles County.
AB - OBJECTIVE: Use of administrative data from child welfare (CW) and mental health
systems in Los Angeles County provided a unique opportunity to more closely
examine mental health needs of children dually served by these systems. This
study examined the presence of mental disorders and correlates of receipt of
mental health services by diagnostic classification in this population. METHODS:
Data were obtained for 3,191 children receiving services from Los Angeles
County's Department of Children and Family Services and Department of Mental
Health (DMH) between July 2011 and July 2012. Multivariate linear and logistic
regression models examined the relationship between sociodemographic and CW
related characteristics and receipt of outpatient services by clinician-diagnosed
mental disorder. RESULTS: Of the 3,191 referred children, 68% met criteria for
one of the four diagnostic classifications. Mood disorders were the most common
diagnosis (30%), followed by anxiety disorders (20%), behavior disorders (9%),
and attention-deficit hyperactivity disorder (9%). Children with prior DMH
involvement received more services regardless of diagnosis. Older children (ages
>=15) received more services than younger children, whereas younger children were
more likely to receive family therapy. Race-ethnicity did not play a significant
role in predicting service receipt. CONCLUSIONS: The unique mental health needs
of CW-involved children were exemplified by the differences found in the
percentages of children with diagnoses of mental disorders between this sample
and children in the general population. Because of family and placement
disruptions among CW-involved children, it is important that the provision of
individual therapy is not overlooked in favor of family therapy.
PMID- 28412893
TI - Public Attitudes and Feelings of Warmth Toward Women and Men Experiencing
Depression During the Perinatal Period.
AB - OBJECTIVE: Depression is a major public health concern and often goes untreated.
In response to a growing body of research documenting stigma as a barrier to
depression care, this study focused on examining public stigma toward potentially
vulnerable subpopulations. METHODS: Participants (N=241) were recruited from
Amazon's Mechanical Turk and randomly assigned to provide anonymous ratings on
attitudes and feelings of warmth toward pregnant women and expectant fathers
experiencing depression, mothers and fathers experiencing postpartum depression,
or women and men experiencing depression during nonperinatal periods. RESULTS:
Participants reported significantly more negative attitudes about depressed men
than women, and male participants reported significantly more negative attitudes
than female participants toward depressed individuals. Similarly, participants
felt significantly less warmth toward depressed men than women, and male
participants expressed significantly less warmth than female participants toward
depressed individuals. Male participants felt equally warm toward men and women
who experienced depression during nonperinatal periods, whereas female
participants felt significantly warmer toward women who experienced depression
during nonperinatal periods compared with men. CONCLUSIONS: Results indicate that
the public views depressed men more negatively than depressed women and that
males are more likely to hold stigmatizing attitudes toward depression,
suggesting the importance of reducing stigma directed toward men with depression
and stigma held by men toward persons with depression. Attitudes and feelings
toward depressed individuals did not consistently vary by perinatal status. These
findings are an initial step in improving depression treatment engagement
strategies and in identifying those who would benefit most from stigma reduction
programs.
PMID- 28412892
TI - Is There a Role for Fidelity Self-Assessment in the Individual Placement and
Support Model of Supported Employment?
AB - OBJECTIVE: Fidelity assessments help ensure that evidence-based practices are
implemented properly. Although assessments are typically conducted by independent
raters, some programs have implemented self-assessments because of resource
constraints. Self-assessments were compared with independent assessments of
programs implementing individual placement and support supported employment.
METHODS: Eleven community-based outpatient programs in New York State completed
both self- and independent assessments. Intraclass correlation coefficients and
paired t tests were used to compare scores from self- and independent
assessments. RESULTS: For both assessment methods, mean scores for all programs
were within the range of fair fidelity. Self- and independent assessment total
scores were not significantly different; however, significant differences were
found on some scale items in this small sample. CONCLUSIONS: Self-assessment may
be valid for examining a program's overall functioning and useful when resource
constraints prevent independent assessment. Independent assessors may be able to
identify nuances, particularly on individual assessment items, that can point to
areas for program improvement.
PMID- 28412894
TI - Mental Health Treatment Seeking Among Veteran and Civilian Community College
Students.
AB - OBJECTIVE: A Web-based survey examined treatment seeking among community college
students to inform the design of engagement interventions. METHODS: Veteran and
civilian community college students (N=765) were screened for mental disorders
and reported perceptions of treatment need, effectiveness, and stigma, as well as
service use. Regression analysis identified predictors of pharmacotherapy and
psychotherapy use. RESULTS: Of the 511 students who screened positive for a
current mental disorder or reported a perceived need for treatment (149 veterans
and 362 civilians), 30% reported past-year use of psychotropic medications.
Predictors were perceived treatment need (odds ratio [OR]=7.81, p<.001) and the
perception that psychotropic medications are effective (OR=3.38, p=.012). Eleven
percent of participants reported past-year psychotherapy use, and predictors were
a positive screen for posttraumatic stress disorder (OR=2.78, p=.04) and poorer
financial status. CONCLUSIONS: Modifiable barriers, including perceived need for
and effectiveness of treatment, were correlated with pharmacotherapy use and
should be targeted by engagement interventions.
PMID- 28412895
TI - Self-Stigma and Consumer Participation in Shared Decision Making in Mental Health
Services.
AB - OBJECTIVE: People with mental illness struggle with symptoms and with public
stigma. Some accept common prejudices and lose self-esteem, resulting in shame
and self-stigma, which may affect their interactions with mental health
professionals. This study explored whether self-stigma and shame are associated
with consumers' preferences for participation in medical decision making and
their behavior in psychiatric consultations. METHODS: In a cross-sectional study
conducted in Germany, 329 individuals with a diagnosis of a schizophrenia
spectrum disorder or an affective disorder and their psychiatrists provided
sociodemographic and illness-related information. Self-stigma, shame, locus of
control, and views about clinical decision making were assessed by self-report.
Psychiatrists rated their impression of the decision-making behavior of
consumers. Regression analyses and structural equation modeling were used to
determine the association of self-stigma and shame with clinical decision making.
RESULTS: Self-stigma was not related to consumers' participation preferences, but
it was associated with some aspects of communicative behavior. Active and
critical behavior (for example, expressing views, daring to challenge the
doctor's opinion, and openly speaking out about disagreements with the doctor)
was associated with less shame, less self-stigma, more self-responsibility, less
attribution of external control to powerful others, and more years of education.
CONCLUSIONS: Self-stigma and shame were associated with less participative and
critical behavior, which probably leads to clinical encounters that involve less
shared decision making and more paternalistic decision making. Paternalistic
decision making may reinforce self-stigma and lead to poorer health outcomes.
Therefore, interventions that reduce self-stigma and increase consumers' critical
and participative communication may improve health outcomes.
PMID- 28412896
TI - Disparities in Health Care Utilization and Functional Limitations Among Adults
With Serious Psychological Distress, 2006-2014.
AB - OBJECTIVE: This study compared health care access, utilization, and functional
indicators among adults with and without serious psychological distress (SPD) in
the years surrounding implementation of the Patient Protection and Affordable
Care Act (ACA). METHODS: Adults ages 18 to 64 from the 2006-2014 National Health
Interview Survey (N=207, 853) were examined on 11 access, utilization, and
functional indicators: health insurance coverage (health coverage), insufficient
money for medications, delay in health care (delay in care), insufficient money
for health care, visiting a doctor ten or more times in the past 12 months,
change in place of health care, change in place of health care due to insurance,
limitations in ability to work, limitations in activities of daily living (ADLs),
insufficient money for mental health care, and having seen a mental health care
provider. RESULTS: Multivariate models that were adjusted for health coverage and
sociodemographic characteristics indicated that compared with adults without SPD,
adults with SPD had greater odds of lacking money for medications (AOR=10.0) and
health care (AOR=3.1), experiencing delays in care (AOR=2.7), visiting a doctor
ten or more times in the past 12 months (AOR=3.2), changing usual place of health
care (AOR=1.5), changing usual place of health care because of insurance
(AOR=1.5), and experiencing limitations in ADLs (AOR=3.6) and ability to work
(AOR=1.8). The proportions of adults with SPD who lacked health coverage and
money to buy prescriptions increased during the study period. Although this trend
reversed in 2014, the proportion with SPD experiencing barriers remained above
2006 levels. CONCLUSIONS: Health care patterns among adults with SPD require
greater attention.
PMID- 28412897
TI - Rates of Cervical Cancer Screening Among Women With Severe Mental Illness in the
Public Health System.
AB - OBJECTIVE: This study aimed to determine cervical cancer screening rates among
women with severe mental illness. METHODS: California Medicaid administrative
records (2010-2011) for 31,308 women with severe mental illness were examined.
Participants received specialty mental health services and were not dually
eligible for Medicare. Poisson models assessed association between selected
predictors and cervical cancer screening. RESULTS: Overall, 20.2% of women with
severe mental illness received cervical cancer screening during the one-year
period. Compared with white women, Asian women (adjusted risk ratio [ARR]=1.23),
black women (ARR=1.10), and Hispanic women (ARR=1.11) (p<.001) were more likely
to have been screened. Women ages 28-37 were more likely than those ages 18-27 to
have been screened (ARR=1.31, p<.001). Evidence of other health care use was the
strongest predictor of screening (ARR=3.07, p<.001). CONCLUSIONS: Most women in
the sample were not regularly screened for cervical cancer. Cervical cancer
screening for this high-risk population should be prioritized.
PMID- 28412898
TI - A Collaborative Process for Evaluating Infant Mental Health Home Visiting in
Michigan.
AB - This column describes an innovative collaboration in Michigan that could serve as
a model for meaningful community-university-state partnerships. Recent
legislation in Michigan threatened the infant mental health home visiting
program, a service for Medicaid-eligible infants, toddlers, and families affected
by mental illness. The University of Michigan is overseeing two major studies in
collaboration with the Michigan Department of Health and Human Services, the
Michigan Association for Infant Mental Health, the Michigan Infant Toddler
Research Exchange faculty network, and community health service providers to
determine the evidence base for the program and ensure its future success.
PMID- 28412899
TI - Monitoring of Patients on Second-Generation Antipsychotics: A National Survey of
Child Psychiatrists.
AB - OBJECTIVE: The survey assessed self-reported monitoring by child psychiatrists of
children prescribed second-generation antipsychotics, facilitators and barriers
to monitoring, and steps taken to adhere to monitoring. METHODS: The authors
anonymously surveyed 4,144 U.S. child psychiatrists. Descriptive statistics and
multiple linear regressions were utilized to describe results and identify
correlates of monitoring. RESULTS: Among responders (N=1,314, 32%), over 95% were
aware of all guidelines, over 80% agreed with most guidelines, but less than 20%
had adopted and adhered to most guidelines. Awareness of guidelines, working
within an academic practice, and fewer years in practice predicted adherence.
CONCLUSIONS: Child psychiatrists have generally not adopted the guidelines for
monitoring children on second-generation antipsychotics. Interventions to improve
monitoring should target child psychiatrists in nonacademic practices and those
who have been out of training for longer periods. Future research should assess
family barriers to monitoring.
PMID- 28412900
TI - Reducing Behavioral Health Inpatient Readmissions for People With Substance Use
Disorders: Do Follow-Up Services Matter?
AB - OBJECTIVE: Individuals with substance use disorders are at high risk of hospital
readmission. This study examined whether follow-up services received within 14
days of discharge from an inpatient hospital stay or residential detoxification
reduced 90-day readmissions among Medicaid enrollees whose index admission
included a substance use disorder diagnosis. METHODS: Claims data were analyzed
for Medicaid enrollees ages 18-64 with a substance use disorder diagnosis coded
in any position for an inpatient hospital stay or residential detoxification in
2008 (N=30,439). Follow-up behavioral health services included residential,
intensive outpatient, outpatient, and medication-assisted treatment (MAT).
Analyses included data from ten states or fewer, based on a minimum number of
index admissions and the availability of follow-up services or MAT. Survival
analyses with time-varying independent variables were used to test the
association of receipt of follow-up services and MAT with behavioral health
readmissions. RESULTS: Two-thirds (67.7%) of these enrollees received no follow
up services within 14 days. Twenty-nine percent were admitted with a primary
behavioral health diagnosis within 90 days of discharge. Survival analyses showed
that MAT and residential treatment were associated with reduced risk of 90-day
behavioral health admission. Receipt of outpatient treatment was associated with
increased readmission risk, and, in only one model, receipt of intensive
outpatient services was also associated with increased risk. CONCLUSIONS:
Provision of MAT or residential treatment for substance use disorders after an
inpatient or detoxification stay may help prevent readmissions. Medicaid programs
should be encouraged to reduce barriers to MAT and residential treatment in order
to prevent behavioral health admissions.
PMID- 28412901
TI - An Analysis of Central Residues Between Ligand-Bound and Ligand-Free Protein
Structures Based on Network Approach.
AB - BACKGROUND: Depiction of protein structures as networks of interacting residues
has enabled us to understand the structure and function of the protein. Previous
investigations on closeness centrality have identified protein functional sites
from three- dimensional structures. It is well recognized that ligand binding to
a receptor protein induces a wide range of structural changes. OBJECTIVE: An
interesting question is how central residues function during conformational
changes triggered during ligand binding? The aim of this study is to comprehend
at what extent central residues change during ligand binding to receptor
proteins. METHOD: To determine this, we examined 37 pairs of protein structures
consisting of ligand-bound and ligand-free forms. These protein structures were
modelled as an undirected network and significant central residues were obtained
using residue centrality measures. In addition to these, the basic network
parameters were also analysed. RESULTS: On analysing the residue centrality
measures, we observed that 60% of central residues were common in both the ligand
bound and ligand-free states. The geometry of the central residues revealed that
they were situated closer to the protein center of the mass. Finally, we
demonstrated the effectiveness of central residues in amino acids substitutions
and in the evolution itself. The closeness centrality was also analyzed among
different protein domain sizes and the values gradually declined from single
domains to multi-domain proteins suggesting that the network has potential for
hierarchical organization. Betweenness centrality measure was also used to
determine the central residues and 31% of these residues were common between the
holo/apo states. CONCLUSION: Findings reveal that central residues play a
significant role in determining the functional properties of proteins. These
results have implications in predicting binding/active site residues,
specifically in the context of drug designing, if additional information
concerning ligand binding is exploited.
PMID- 28412902
TI - Nanosafety: Towards Safer Nanoparticles by Design.
AB - The continuous development of Nanotechnology is progressively introducing
nanoparticles into society. However, little is known about the safety of
nanoparticles and functions of engineered nanomaterials, in particular how the
physicochemical properties of the materials relate to mechanisms of injury at the
nano-bio interface. While comprehensive knowledge on the potential toxicity of
NPs is still lacking, as time goes by and research in the field continues,
different aspects, such as interactions with the immune system, perturbation of
cellular membranes, transportation of toxic moieties and others are emerging as
potentially hazardous aspects of NPs. As a result, this rapidly advancing new
field requires the development of novel test strategies based on the contribution
of toxicological pathways to the pathophysiology of disease that allow complex
toxicants to be screened in robust, mechanism-based assays in which the bulk of
the investigation can be carried out at the cellular and biomolecular level
whilst maintaining limited animal use. A review of these strategies will help to
provide guidelines for synthetic nanochemists on how to design NPs to be safe
during their full life cycle while maintaining their parental desired properties.
PMID- 28412903
TI - Phage Life Cycles Behind Bacterial Biodiversity.
AB - Bacteriophages (phages or bacterial viruses) are the most abundant biological
entities in our planet; their influence reaches far beyond the microorganisms
they parasitize. Phages are present in every environment and shape up every
bacterial population in both active and passive ways. They participate in the
circulation of organic matter and drive the evolution of microorganisms by
horizontal gene transfer at unprecedented scales. The mass flow of genetic
information in the microbial world influences the biosphere and poses challenges
for science and medicine. The genetic flow, however, depends on the fate of the
viral DNA injected into the bacterial cell. The archetypal notion of phages only
engaging in predatorprey relationships is slowly fading. Because of their varied
development cycles, environmental conditions, and the diversity of microorganisms
they parasitize, phages form a dense and highly complex web of dependencies,
which has important consequences for life on Earth. The sophisticated phage
bacteria interplay includes both aggressive action (bacterial lysis) and
"diplomatic negotiations" (prophage domestication). Here, we review the most
important mechanisms of interactions between phages and bacteria and their
evolutionary consequences influencing their biodiversity.
PMID- 28412904
TI - The Role of Exosomes and Exosome-derived microRNAs in Atherosclerosis.
AB - BACKGROUND: Atherosclerosis is the leading cause of death and morbidity
throughout industrialized nations, accounting for one-fifth of all deaths
globally. Exosomes are bi-lipid membranous vesicles containing protein, lipid and
nucleic acid contents that are released from the cells via the endolysosomal
pathway. Exosomes are derived from several cells including macrophages, dendritic
cells, platelets as well as human serum. METHODS: In this review, an overview of
recent advances, the evidence for the role of exosomes and exosomederived
microRNAs (miRNAs) in atherosclerosis are provided. RESULTS: Recent evidence has
shown that exosomes derived from the cells mentioned above are involved in
atherosclerosis, whose secretion appears to be regulated by various natural and
experimental stimuli, physiological and pathological processes. CONCLUSION:
Exosomes are now accepted as specifically secreted vesicles that enable
intercellular communications and have become exponentially interesting to be used
as the possible relevant biomarkers in disease development such as cadiovascular
disease, particular in atherosclerosis in addition to their minimally invasive
clinical diagnosis.
PMID- 28412905
TI - Therapeutic Potential of Heme Oxygenase-1/carbon Monoxide System Against Ischemia
Reperfusion Injury.
AB - BACKGROUND: Ischemia-reperfusion (I/R) injury causes the dysfunctions of
different major organs, leading to morbidity and mortality on the global scale.
Among a battery of therapeutic targets, the heme oxygenase- 1 (HO-1)/carbon
monoxide (CO) system has been evaluated for the development of new therapies
against I/R injury. The enzyme HO-1 catalyzes the degradation of heme into three
biologically active end products, namely biliverdin/bilirubin, CO and ferrous
ion. Interestingly, CO is one of a few bioactive gaseous molecules with the
capability of regulating inflammation, cell survival and growth. In fact, several
CO-releasing compounds have been developed for directly reprogramming the
intracellular apoptotic, inflammatory and proliferative signaling networks. In
parallel, chemical and genetic approaches have also been evaluated for up
regulating HO-1 expression as an endogenous mechanism to ameliorate I/R injury
and heal wounds. METHODS: In this review, we discussed the recent studies on the
therapeutic potential of HO-1/CO system in the treatment of I/R injury in the
heart, brain, liver, kidney, lung, intestine and retina. We focused on the
activities and underlying mechanisms of various therapeutic strategies to
regulate HO-1/CO system against I/R injury. RESULTS: A large number of studies
have demonstrated that HO-1/CO system exhibits potent anti-oxidative,
antiapoptotic, anti-inflammatory and cytoprotective activities against I/R
injury. The regulation of HO-1/CO expression has been achieved either by genetic
overexpression of HO-1 cDNA or pharmacological induction with drugs including
curcumin and resveratrol. CONCLUSION: The HO-1/CO system is a potential target
for treating I/R injury. Further studies should be directed to in vivo efficacy
and clinical application of HO-1/CO system in the therapy of I/R injury.
PMID- 28412906
TI - Combined Approach of QSAR and Docking Studies for the Design of Local Anaesthetic
Agents.
AB - BACKGROUND: Heterocyclic scaffold, benzotriazole and its derivatives are
potential anaesthetic agents that act locally. OBJECTIVE: QSAR and docking
analysis of previously synthesized benzotriazolyl derivatives were modelled for
their local anaesthetic action using computer assisted multiple regression
analysis. It provides the insight about the structural requirements for the local
anaesthetic action. METHOD: A training set comprising of 16 molecules and test
set of 8 molecules were selected for present investigation by using sphere
exclusion method with dissimilarity value of +4.0. The validation of the QSAR
models was performed by cross-validation and external test set prediction.
Docking studies was performed using GRIP docking methodology. RESULTS &
CONCLUSION: Further GRIP docking with the pentameric ligand gated ion channel,
2XQ3 facilitated the mechanistic analysis of interactions of the test molecules
active site residues.
PMID- 28412907
TI - Review of the Pharmacology of the Emerging Possibilities of the Direct Oral
Anticoagulants' Reversal.
AB - BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable
anticoagulation, oral administration with good patient compliance and a good
safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and
rivaroxaban - direct factor Xa inhibitors are now largely used for
anticoagulation in patients with nonvalvular atrial fibrillation and in patients
with venous thromboembolism. These agents have emerged as an expediential
clinical choice in long-term anticoagulation for an increasing number of
patients. Despite their advantages, concerns persist about a lack of rapid
reversal agents in urgent clinical situations. METHODS: This review is focused on
the pharmacology of nonspecific and target-specific reversal agents for DOACs
induced anticoagulation. A systemic review of preclinical and clinical studies
published in peer-reviewed scientific journals was performed. RESULTS AND
CONCLUSIONS: Fresh frozen plasma and coagulation factors concentrates might be
considered in bleeding emergencies; however, there is a lack of larger studies
confirming the efficacy of coagulation factors concentrates for the reversal of
DOACs-induced anticoagulation, and a particular risk of coagulation factors
concentrates-induced thrombosis. Recently, idarucizumab has been approved
commercially for acute reversal of dabigatran in emergencies as a first target
specific reversal agent. Moreover, andexanet alpha and aripazine are being
extensively studied in several phase II and III clinical studies. It is likely
that more target-specific agents for reversal of DOACs-induced anticoagulation
will be introduced to clinical practice in near future.
PMID- 28412908
TI - News in the Indications of Direct Oral Anticoagulants According to the American
College of Chest Physicians 2016 Guidelines.
AB - BACKGROUND: The 10th edition of the CHEST Guideline and Expert Panel Report for
the treatment of venous thromboembolism (VTE) was recently updated with
recommendations on both the choice of anticoagulants and the duration of
treatment in diverse clinical scenarios. METHOD: In this paper, we focus on news
in the use of direct oral anticoagulants (DOACS), a group of synthetic low
molecular weight drugs capable of directly and specifically inhibiting either
activated factor X or both free and fibrin- bound thrombin. RESULTS: New to the
guidelines is the recommendation of the use of DOACS over vitamin K-antagonists
(VKA's) in individuals without cancer who develop VTE. The choice and intensity
of anticoagulants is the same for lower and upper extremity thrombosis or for
pulmonary embolism. For cancer-related thrombosis low molecular weight heparin is
still recommended over the use of VKA's or DOACS, though high quality evidence
for this choice is lacking. If therapy is given beyond three months, remaining on
the same anticoagulant is suggested. Re-thrombosis while on regular use of DOACs
requires switching to low molecular weight heparins at least for one month.
CONCLUSION: Ultimately the choice of anticoagulant will depend on patient
specific factors such as comorbidities, compliance, patient preferences,
availability and costs. We address the news in DOAC use in VTE from the
perspective of an upper-middle income economy.
PMID- 28412909
TI - Prolonged Perfusion Predicts Recurrent Ischemic Stroke but not Transient Ischemic
Attack in Patients with Symptomatic Intracranial Stenosis.
AB - BACKGROUND: Intracranial arterial stenosis (ICAS) is the dominant cause for
ischemic stroke worldwide, with hemodynamic compromise as a crucial contributor.
Prolonged perfusion is commonly observed in ICAS patients on CT perfusion (CTP)
maps, while the clinical significance of this perfusion pattern has not been
elucidated. METHOD: Patients having symptomatic ICAS of 50-99% stenosis with
sustained downstream cerebral blood flow (CBF) were enrolled in this study.
Prolonged perfusion was defined as increased mean transit time (MTT) in vascular
territories of the target ICAS on CTP maps. The primary clinical outcome was
recurrence of ipsilateral ischemic stroke, and secondary outcome was any
ipsilateral ischemic events at 2 years follow-up. RESULTS: Of the 95 patients
(median age 61y; 70% males) with symptomatic ICAS, 29 patients (30.5%) had
prolonged perfusion. Such delayed perfusion was persistent in a majority of
patients according to the 1-year imaging follow-up. The prolongation of cerebral
perfusion was associated with subsequent risk for ipsilateral ischemic stroke (HR
7.01; 95% CI 1.86-26.46; p = 0.004), but not for any ipsilateral ischemic events
(HR 1.52; 95% CI 0.63-3.68; p = 0.348). Further comparison of perfusion measures
showed lower CBF (p = 0.034) and higher MTT (p = 0.064) in patients with
recurrent ischemic stroke, but not in those with recurrent transient ischemic
attack (TIA). Among patients with recurrent stroke, a majority had multiple
infarcts along the borderzone regions. CONCLUSION: In patients with symptomatic
ICAS, persistent prolonged cerebral perfusion might contribute to the relapse of
ischemic stroke, but not TIA.
PMID- 28412911
TI - Pharmacological Therapy of Abdominal Aortic Aneurysm: An Update.
AB - BACKGROUND: Abdominal aortic aneurysm (AAA), a progressive segmental abdominal
aortic dilation, is associated with high mortality. AAA is characterized by
inflammation, smooth muscle cell (SMC) depletion and extracellular matrix (ECM)
degradation. Surgical intervention and endovascular therapy are recommended to
prevent rupture of large AAAs. Unfortunately, there is no reliable
pharmacological agent available to limit AAA expansion. In the past decades,
extensive investigations and a body of ongoing clinical trials aimed at defining
potent treatments to inhibit and even regress AAA growth. CONCLUSION: In this
review, we summarized recent progress of potential strategies, particularly
macrolides, tetracyclines, statins, angiotensin converting enzyme inhibitors,
angiotensin receptor blocker, corticosteroid, anti-platelet drugs and mast cell
stabilizers. We also consider recently identified novel molecular targets, which
have potential to be translated into clinical practice in the future.
PMID- 28412912
TI - The Socioeconomic Effects of Uncontrolled Hypertension.
AB - BACKGROUND: Hypertension (HT), albeit a modifiable risk factor of cardiovascular
morbidity and mortality, remains one of the main contributors to the total
disease burden internationally and, thus, inevitably one of the basic cost
drivers in healthcare systems. CONCLUSION: Taking the above into account, this
brief narrative review aims at presenting the main findings of the international
health economics literature on HT with regards to four key areas: a) the costs
attributable to HT, b) the effects of HT on patient well-being, c) the cost
effectiveness of pharmaceutical interventions against high blood pressure, and,
d) the costs and benefits of preventive measures against HT. Bearing in mind the
available evidence on disease costs and the efficiency of interventions, HT must
constitute a primary objective of modern health policy, internationally.
PMID- 28412913
TI - Anti-Carcinogenic Effects of Carnosol-An Updated Review.
AB - BACKGROUND: Despite the newly treatment procedures, cancer is considered as the
main health threat nowadays and, therefore, new therapeutic options such as
traditional medicine should be investigated. Rosemary (Rosmarinus officinalis L.)
has been found to possess antitumor effects due to its major ingredients,
including carnosic acid, carnosol, ursolic acid, and rosmarinic acid. OBJECTIVE:
This study was designed to gather the recent literature findings from 2010 to
2016 on the cancer anti-tumor activities of carnosol and probably involved
mechanisms. METHOD: The online English papers were gathered through various
search websites, including PubMed, Iran Medex, Medline, Google Scholar, and
Scopus from 2010 to 2016. RESULTS: Carnosol, the specific composition of
rosemary, has been shown to have beneficial effects in keeping humans healthy and
may be acted as an antitumor agent. CONCLUSION: This review revealed that
carnosol may be effective as an anti-tumor agent in the different types of cancer
by inducing apoptosis and inhibiting the cell cycle division. However, more
studies are needed to confirm carnosol therapeutic effects in human.
PMID- 28412910
TI - Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity.
AB - BACKGROUND: The treatment of schizophrenia is challenging due to the wide range
of symptoms (positive, negative, cognitive) associated with the disease. Typical
antipsychotics that antagonize D2 receptors are effective in treating positive
symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical
antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating
cognitive and negative symptoms compared to typical antipsychotics, but these
drugs also result in side-effects such as metabolic syndromes. OBJECTIVE: To
identify evidence in the literature that elucidates the pharmacological profile
of aripiprazole.s. METHODS: We searched PubMed for peer reviewed articles on
aripiprazole and its clinical efficacy, side-effects, pharmacology, and effects
in animal models of schizophrenia symptoms. RESULTS: Aripiprazole is a newer
atypical antipsychotic that displays a unique pharmacological profile, including
partial D2 agonism and functionally selective properties. Aripiprazole is
effective at treating the positive symptoms of schizophrenia and has the
potential to treat negative and cognitive symptoms at least as well as other
atypical antipsychotics. The drug has a favorable side-effect profile and has a
low propensity to result in EPS or metabolic syndromes. Animal models of
schizophrenia have been used to determine the efficacy of aripiprazole in symptom
management. In these instances, aripiprazole resulted in the reversal of deficits
in extinction, pre-pulse inhibition, and social withdrawal. Because aripiprazole
requires a greater than 90% occupancy rate at D2 receptors to be clinically
active and does not produce EPS, this suggests a functionally selective effect on
intracellular signaling pathways. CONCLUSION: A combination of factors such as
dopamine system stabilization via partial agonism, functional selectivity at D2
receptors, and serotonin-dopamine system interaction may contribute to the
ability of aripiprazole to successfully manage schizophrenia symptoms. This
review examines these mechanisms of action to further clarify the pharmacological
actions of aripiprazole.
PMID- 28412915
TI - Early Functional and Structural Microvascular Changes in Hypertension Related to
Aging.
AB - It is becoming increasingly clear that both microvascular network alterations and
subsequent tissue perfusion defects may precede and predict the development of
arterial hypertension and other cardiovascular and metabolic diseases, including
diabetes and metabolic syndrome. Moreover, the subsequent functional and
structural alterations in microvascular reactivity and density, as well as
alterations in the macrocirculation characteristic of physiologic vascular aging,
contribute to the development of target organ damage. Microvascular rarefaction
appears to be an early vascular structural alteration in the setting of
hypertension, as it is already present in individuals presenting with borderline
hypertension and normotensive young adults with a familial predisposition to high
blood pressure. The chronic increases in blood pressure that occur during
senescence secondary to macrocirculatory changes induce vasoconstriction within
the microcirculation, which promotes the development of tissue hypoxia and
reduces both arteriolar and capillary density. This phenomenon contributes to
additional increases in peripheral vascular resistance and establishes a vicious
cycle that culminates in both tissue injury and target organ damage, which are
equally present in senescence and hypertension. Therefore, the microcirculation
may be considered an essential target for both the pharmacological and non
pharmacological treatment of arterial hypertension and other cardiovascular
diseases.
PMID- 28412914
TI - Early Vascular Ageing (EVA): Definitions and Clinical Applicability.
AB - Arterial stiffness has been accumulating evidence as an intermediate
cardiovascular endpoint. It has been established as an independent risk marker
for cardiovascular disease, and reflects the dissociation between chronologic and
biologic age of large arteries-attributing earlier the risk that a normal
vascular ageing process had installed to occur several years later. The concept
of Early Vascular Ageing (EVA) is developed to establish primordial prevention,
identifying individuals whose ageing path has been accelerated either by inherent
features, interaction with the environment or arterial exposure to several types
of insults that evolve to medial layer morphological changes. Understanding the
pathophysiology of vascular ageing, its consequences and therapeutic
opportunities is therefore an advantage that could be translated in time of
prevention and survival free of cardiovascular disease. As the EVA construct is
advancing, new features appear as interesting to better translate it into
clinical practice.
PMID- 28412916
TI - Cannabis; Epidemiological, Neurobiological and Psychopathological Issues: An
Update.
AB - BACKGROUND: Cannabis is the illicit drug with both the largest current levels of
consumption and the highest reported lifetime prevalence levels in the world.
Across different countries, the prevalence of cannabis use varies according to
the individual income, with the highest use being reported in North America,
Australia and Europe. Despite its 'soft drug' reputation, cannabis misuse may be
associated with several acute and chronic adverse effects. OBJECTIVE: The present
article aims at reviewing several papers on epidemiological, neurobiological and
psychopathological aspects of the use of cannabis. The PubMed database was here
examined in order to collect and discuss a range of identified papers.
DISCUSSION: Cannabis intake usually starts during late adolescence/early
adulthood (15-24 years) and drastically decreases in adulthood with the
acquisition of working, familiar and social responsibilities. Clinical evidence
supports the current socio-epidemiological alarm concerning the increased
consumption among youngsters and the risks related to the onset of psychotic
disorders. The mechanism of action of cannabis presents some analogies with other
abused drugs, e.g. opiates. Furthermore, it has been well demonstrated that
cannabis intake in adolescence may facilitate the transition to the use and/or
abuse of other psychotropic drugs, hence properly being considered a 'gateway
drug'. Some considerations on synthetic cannabimimetics are provided here as
well. CONCLUSION: In conclusion, the highest prevalence of cannabis use and the
social perception of a relatively low associated risk are in contrast with
current knowledge based on biological and clinical evidence. Indeed, there are
concerns relating to cannabis intake association with detrimental effects on both
cognitive impairment and mental health.
PMID- 28412917
TI - Is there a Teratogenicity Risk Associated with Cannabis and Synthetic
Cannabimimetics' ('Spice') Intake?
AB - BACKGROUND: Substance use, including cannabis, has been documented amongst women
both in the pre-conception period and during pregnancy, particularly during the
1st trimester, which is clearly the most critical period in the organogenesis.
The recent emergence on the drug market of synthetic cannabimimetics/SC ('spice')
may represent a new challenge for clinicians. OBJECTIVE: A literature overview on
the teratogenicity profile of both cannabis and synthetic cannabimimetics was
here carried out. METHOD: The PubMed database was searched in order to collect
all relevant cases and data regarding the possible evidence of teratogenicity
issues associated with cannabis and SC intake. RESULTS: The use of cannabis in
pregnant women has been associated with a plethora of both obstetrical/
gestational complications and neurobehavioral/neurological effects on newborns.
Conversely, only few and conflicting data are related to SC misuse issues.
CONCLUSION: Although cannabis use may be considered a risk factor for the
occurrence of pregnancyrelated morbidity issues, many studies relied on self
reports and showed inconsistent results when controlling for potential
confounders, including tobacco use. Given the role of the endocannabinoid system
in both pregnancy and delivery, SC potency at interacting with the
endocannabinoid system may be a reason of concern. Clinicians should carefully
assess each woman planning a pregnancy, or who is pregnant already, and who is at
risk of persisting in her current cannabis and/or SC intake. A nonjudgmental
approach, aiming at collecting both a history of drug/alcohol use and at
providing information regarding the risks associated with cannabis/SC intake
during pregnancy is here advised.
PMID- 28412918
TI - Neurological Aspects of Medical Use of Cannabidiol.
AB - BACKGROUND: Cannabidiol (CBD) is among the major secondary metabolites of
Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is
a resorcinol-based compound with a broad spectrum of potential therapeutic
properties, including neuroprotective effects in numerous pathological
conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory
activities and the modulation of a large number of brain biological targets
(receptors, channels) involved in the development and maintenance of
neurodegenerative diseases. OBJECTIVE: The aim of the present review was to
describe the state of art about the pre-clinical research, the potential use and,
when existing, the clinical evidence related to CBD in the neurological field.
METHOD: Collection of all the pre-clinical and clinical findings carried out
investigating the effects of CBD alone, not in combination with other substances,
in the neurological arena with the exclusion of studies on neuropsychiatric
disorders. RESULTS: Laboratory and clinical studies on the potential role of CBD
in Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS),
Huntington's disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia,
were examined. CONCLUSION: Pre-clinical evidence largely shows that CBD can
produce beneficial effects in AD, PD and MS patients, but its employment for
these disorders needs further confirmation from well designed clinical studies.
CBD pre-clinical demonstration of antiepileptic activity is supported by recent
clinical studies in human epileptic subjects resistant to standard antiepileptic
drugs showing its potential use in children and young adults affected by
refractory epilepsy. Evidence for use of CBD in PD is still not supported by
sufficient data whereas only a few studies including a small number of patients
are available.
PMID- 28412919
TI - Neurological Disorders in Medical Use of Cannabis: An Update.
AB - BACKGROUND & OBJECTIVE: Medical cannabis is increasingly used as a treatment or
adjunct treatment with different levels of efficacy in several neurological
disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and
Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain,
epilepsy, headache), as well as in other medical conditions (e.g. nausea and
vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions,
asthma). Nevertheless, a number of neurological adverse effects from use of
medical cannabis on the short- and on the longterm have been reported, in
addition to other adverse health events. CONCLUSION: It has been noticed that the
use of medical cannabis can lead to a paradoxical effects depending on the amount
of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain.
Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis,
seizures, epilepsy, headache) may be caused or exacerbated by the same treatment
supposed to cure them. The current review presents an update of the neurological
adverse effects resulting from the use of cannabis for medical purposes,
highlighting the need to weigh the benefits and risks, when using
cannabinoidbased treatments.
PMID- 28412920
TI - Neuropsychiatric and General Interactions of Natural and Synthetic Cannabinoids
with Drugs of Abuse and Medicines.
AB - BACKGROUND & OBJECTIVE: Cannabis is the most widely used illicit drug. The two
most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and
cannabidiol (CBD). The THC content of cannabis has been increasing during the
last years and recently appeared in the market as a series of synthetic
cannabinoids with potent agonist activity. Recreational users frequently combine
cannabis with other drugs of abuse as alcohol, amphetamines and derivatives,
nicotine and cocaine. In addition, these subjects can be taking medicines for
acute and chronic medical conditions. The increasing use of medicinal cannabis
for chronic pain and neurological and psychiatric disorders can produce potential
interactions with medications used for the symptomatic treatment of these or
other diseases. CONCLUSION: THC and CBD are metabolized mainly in the liver by
cytochrome P-450 isoenzymes (mainly CYP2Cs and CYP3A4). In vitro studies indicate
that THC and CBD both inhibit CYP1A1, 1A2 and 1B1 enzymes, and recent studies
have indicated that CBD is also a potent inhibitor of CYP2C19 and CYP3A4. Both
cannabinoids may interact with other medications metabolized by the same pathway
or by inducers/inhibitors of the isoenzymes. Cannabis produces sedation, impairs
psychomotor performance, and increases blood pressure and heart rate.
Pharmacodynamic interactions with other sedatives can potentiate the central
effects but can be decreased by psychostimulants. This review focuses on the
interactions between cannabinoids and alcohol, other drugs of abuse, and
prescription medicines.
PMID- 28412921
TI - Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, Psychotic Onset.
AB - BACKGROUND: Synthetic Cannabinoids (SC) are the widest and most diffused class of
Novel Psychoactive Substances. The short- and long- term health risks associated
with the consumption of SC are often unknown to both users and health
professionals. This review aims to provide a synthesis of the most recent and
relevant insights on the pharmacology, clinical and psychopathological aspects of
SC. METHOD: A structured search of two bibliographic databases (PubMed and
Scopus) was undertaken according to inclusion/exclusion criteria. The following
terms "synthetic cannabinoid*", "synthetic cannabimimetic*", "synthetic
cannabis", "synthetic marijuana" and "Spice AND cannabinoid*" were used as search
strings. RESULTS: 162 relevant results, mainly published in the past two years
were revealed. Most results emerged for the keyword "synthetic cannabinoid*",
followed by the combination "Spice* AND "cannabinoid*". Most papers were
epidemiological, forensic, toxicologic, or analytical. The results of studies
were systematized according their contribution to the comprehension of
pharmacological, clinical and psychopathological effects of SC. Fifteen SC
related fatality cases were reviewed according to their histories, pathology and
toxicology findings. CONCLUSION: The findings of this review confirm the
importance of prompt and reliable information available for health professionals
More specific analytic techniques and designed preventive strategies are required
to face unprecedented SC challenge.
PMID- 28412922
TI - Abnormalities in Kynurenine Pathway Metabolism in Treatment-Resistant Depression
and Suicidality: A Systematic Review.
AB - Treatment resistant depression (TRD) and suicidal behavior are among the most
important public health problems and are commonly associated with significant
disability and psychosocial impairment. Although there have been recent advances
in identifying the neurobiological correlates of these complex conditions, their
pathophysiology still remains unclear. Compared to non-suicidal subjects, higher
mean concentrations of inflammatory mediators have been found in both the
periphery and brain of individuals at risk for suicide. Several lines of evidence
suggest that neuroinflammation is accompanied by a dysregulation of the
kynurenine pathway (KP) in both TRD and suicidal individuals, resulting in an
imbalance of neuroactive metabolites. In particular, neuroinflammation may
trigger an increased production of the N-Methyl-D-aspartate (NMDA) receptor
agonist quinolinic acid and a concomitant reduction of neuroprotective
metabolites, potentially causing downstream effects in glutamatergic systems
resulting in depressive symptoms and suicidal behavior. This systematic review of
the current literature is mainly aimed to summarize the most important evidence
pertaining to KP metabolism abnormalities in TRD and suicidal behavior. Targeting
the KP enzymes may provide innovative approaches in the management of both TRD
and suicidality.
PMID- 28412923
TI - FDG-PET/CT Predicts Outcome in Oropharingeal Carcinoma Patients Undergoing
Intensity Modulated Radiation Therapy with Dose Escalation to FDG-avid Tumour
Volumes.
AB - OBJECTIVE: To evaluate the predictive value of FDG-PET/CT parameters on outcome
of oropharyngeal squamocellular cancer (OSCC) patients undergoing helical
tomotherapy (HTT), with dose escalation to FDG-PET/CT positive tumour volumes
using the simultaneous integrated boost (SIB) technique. MATERIALS AND METHODS:
We analysed 41 patients studied by FDG-PET/CT and treated with radical intent
between 2005 and 2014 for OSCC. HTT-SIB was delivered in 30 fractions
concomitantly: 69 Gy, as SIB, to the PET-positive volume (biological target
volume - BTV-PET), both to the primary tumour (T) and lymph nodes (N), 66 Gy to
the T and positive N, 54 Gy to the laterocervical nodes at risk. Selected PET
parameters were recovered: maximum and mean standardized uptake values (SUVmax
and SUVmean, respectively), metabolic tumour volume (MTV) and total lesion
glycolysis (TLG) obtained with different thresholds (40-50-60% of the SUVmax) for
T and N. The correlation between these parameters and the 3-year overall (OS),
cancer specific (CSS), disease free (DFS), local relapse free for T and N (LRFS-T
and LRFS-N) and distant metastasis free (DMFS) survivals was investigated.
RESULTS: The median follow-up was 37 months (range: 3-125). The 3-year OS, CSS,
DFS, LRFST, LRFS-N and DMFS were 86%, 88%, 76%, 83%, 88% and 91%, respectively.
BTVT+ N>30.9cc and BTV-T>22.4cc were correlated with CSS (p=0.02) and OS
(p=0.006) respectively; TLG-T-60>34.6cc was correlated with CSS (p=0.04) and OS
(p=0.01). MTV-T-60>4.4cc could predict a higher risk of relapse/death (CSS:
p=0.033; hazard ratio (HR) =10.92; OS: p=0.01; HR=16.4; LRFS-T: p=0.02; HR=13.90;
LRFS-T+N: p=0.03; HR=6.50). CONCLUSION: PET parameters predicted survival
outcomes and may be considered in the future in the implementation of more
personalized treatment schedules in patients affected by OSCC undergoing
radiotherapy. FDG-PET/CT dose escalated HTT-SIB allowed very promising 3-year
disease control rates in OSCC patients.
PMID- 28412924
TI - Neurons vs. Germline: A War of Hormetic Tradeoffs.
AB - The process of human ageing is significantly dependent upon events which are
currently shaping humanity. One such event is the seemingly inexorable progress
of technology, and specifically, digital communications technology. Technology
and biology are tightly interconnected, and this has a direct relevance on how
our own ageing mechanisms are evolving and adapting to the change. One way
technology may affect biological ageing is based on the concept of information
exposure which acts as a hormetic stimulus and up-regulates neuronal stress
response pathways. In this way, neurons become increasingly more likely to
acquire repair resources and function for longer, with a consequent overall
improvement in healthy lifespan. At the same time, germline repair mechanisms may
need to be downgraded in order to accommodate a tradeoff: a corresponding
escalation of repairs in neurons. In this Opinion paper, it is discussed that how
a meaningful and intentional integration with technology, which hormetically
challenges our cognition, may redress the conflict for resources between the soma
and the germline, and result in a reduction of age-related dysfunction in the
subjects.
PMID- 28412925
TI - Support and Social Contact as a Decisive Meta-Variable in Morbidity and Social
Welfare of the Older Person.
AB - : Bacground: This article tackles social support as a meta-variable that is
reinforced by a set of social variables, which correlate and act as predictors of
social welfare and life quality of the older person. OBJECTIVE: The objective of
the study is to know how social support, networks and social contacts can
influence the health of the elderly person, especially if these are interrelated
factors. METHOD: The population studied are individuals from both sexes living in
Toledo (Spanish people) and who were 65 years of age or over. Several scales were
applied to assess the frequency of and the degree of satisfaction with perceived
social support received from different sources in relation to social support. The
co relational analysis showed significant positive associations between scores
and measures of and social support, social relations, contact and social
networks. RESULTS: We conclude that the support in general is very good, over 90%
of people from the sample have someone who would help if needed. Social and
health factors are interrelated with social support. Social contact can also be
considered as a life quality estimate. He progressive loss of contact over the
years is a social factor that affects the quality of life. CONCLUSION: The meta
analysis we find that social support and the emotional factor, along with social
interactions, have powerful effects on preventing morbidity and mortality, which
are important social indicators. We conclude that social support based on
positive social interactions provides an optimal state of health in the older
person.
PMID- 28412926
TI - Acute Symptomatic Seizures in Geriatric Patients with Multiple Risk Factors - A
Diagnostic Challenge.
AB - BACKGROUND: Acute symptomatic seizures and epileptic disorders are frequent
health problems of elderly patients. An early and reliable distinction of the
seizure etiology is important to ensure adequate treatment, and to prevent
unwarranted diagnostic and therapeutic procedures. METHODS: We review the current
literature based on a MEDLINE search, describe age-related problems in detail,
with particular attention to clinical practice, discuss possible criteria and
potential pitfalls for diagnostics, and provide a compilation of etiologic
factors for acute symptomatic seizures. RESULTS: The most common causes of acute
symptomatic seizures - acute cerebrovascular disorders, metabolic disorders,
traumatic brain injury, meningo-encephalitis, cerebral tumors, and withdrawal of
alcohol and other central agents - are well-defined and seem to permit
straightforward diagnostic and therapeutic strategies. The current classification
of seizures and epileptic syndromes apparently provides clear definitions.
However, multiple age-related risk factors, as well as a reduced discriminatory
power of clinical and technical diagnostic criteria can make the distinction
difficult. CONCLUSION: Typical age-related problems are incomplete or missing
medical history, dementia, oligosymptomatic seizures, inconclusive EEG and
cerebral imaging results, multiple pathological findings and comorbidity with
ambiguous significance, confounding sleep disorders, intake of proconvulsive
drugs, and psychogenic seizures. All diagnostic and therapeutic decisions need to
be based on an integrative and individual approach that includes diagnostic
findings and risk factors, the intake of medications and other agents, and the
social situation of the elderly patient.
PMID- 28412927
TI - Widespread subcutaneous necrosis in spotted fever group Rickettsioses from the
coastal belt of Sri Lanka- a case report.
AB - BACKGROUND: Spotted fever group rickettsioses (SFGR) transmitted mostly by ticks
are increasingly discovered around the World and some of them are either re
emerging or emerging in Sri Lanka. Accidental human infections caused by these
vector borne zoonotic diseases generally give rise to nonspecific acute febrile
illnesses which can be complicated by multi organ involvement carrying high
morbidity and mortality. Nonspecific clinical features and non-availability of
early diagnostic facilities are known to result in delay in the diagnosis of
rickettsial infections. Therefore, awareness of their prevalence and more
importantly their clinical features would be help in the early diagnosis and
institution of appropriate therapy. CASE PRESENTATION: A 39-year-old otherwise
healthy female presented with an acute febrile illness complicated by severe
small joint and large joint arthritis, jaundice, acute kidney injury and
disseminated intravascular coagulation (DIC) mimicking palindromic rheumatism or
severe sepsis. She later developed a widespread fern-leaf pattern necrotic skin
rash with evidence of vasculitis on the palms and soles, aiding the clinical
diagnosis of SFGR. She had very high antibody titres against R. conorii antigen
confirming the diagnosis and recovered completely with anti-rickettsial therapy.
CONCLUSION: We feel that clinicians should be aware of the unusual clinical
presentations such as purpura fulminans and 'fern-leaf' pattern necrotic skin
rash of SFGR infection. Such knowledge would not only benefit those who practice
in tropics with limited diagnostic facilities but also would improve the
management of acute febrile illness in returning travelers who visit endemic
areas.
PMID- 28412928
TI - Poplar stem transcriptome is massively remodelled in response to single or
repeated mechanical stimuli.
AB - BACKGROUND: Trees experience mechanical stimuli -like wind- that trigger
thigmomorphogenetic syndrome, leading to modifications of plant growth and wood
quality. This syndrome affects tree productivity but is also believed to improve
tree acclimation to chronic wind. Wind is particularly challenging for trees,
because of their stature and perenniality. Climate change forecasts are
predicting that the occurrence of high wind will worsen, making it increasingly
vital to understand the mechanisms regulating thigmomorphogenesis, especially in
perennial plants. By extension, this also implies factoring in the recurring
nature of wind episodes. However, data on the molecular processes underpinning
mechanoperception and transduction of mechanical signals, and their dynamics, are
still dramatically lacking in trees. RESULTS: Here we performed a genome-wide and
time-series analysis of poplar transcriptional responsiveness to transitory and
recurring controlled stem bending, mimicking wind. The study revealed that 6% of
the poplar genome is differentially expressed after a single transient bending.
The combination of clustering, Gene Ontology categorization and time-series
expression approaches revealed the diversity of gene expression patterns and
biological processes affected by stem bending. Short-term transcriptomic
responses entailed a rapid stimulation of plant defence and abiotic stress
signalling pathways, including ethylene and jasmonic acid signalling but also
photosynthesis process regulation. Late transcriptomic responses affected genes
involved in cell wall organization and/or wood development. An analysis of the
molecular impact of recurring bending found that the vast majority (96%) of the
genes differentially expressed after a first bending presented reduced or even
net-zero amplitude regulation after the second exposure to bending. CONCLUSION:
This study constitutes the first dynamic characterization of the molecular
processes affected by single or repeated stem bending in poplar. Moreover, the
global attenuation of the transcriptional responses, observed from as early as
after a second bending, indicates the existence of a mechanism governing a fine
tuning of plant responsiveness. This points toward several mechanistic pathways
that can now be targeted to elucidate the complex dynamics of wind acclimation.
PMID- 28412929
TI - Testosterone, territorial response, and song in seasonally breeding tropical and
temperate stonechats.
AB - BACKGROUND: Testosterone facilitates physiological, morphological, and behavioral
changes required for breeding in male vertebrates. However, testosterone
concentrations and the link between its seasonal changes and those in
reproductive behaviors vary greatly among species. To better understand the
impact of tropical and temperate environments and life history factors on this
variation, we have compared testosterone, territorial behavior and song
performance across sequential stages of the breeding season in males of 16
closely related taxa of East African tropical and West European temperate
stonechats (Saxicola spp), which all breed during a short breeding season, but
differ in migratory behavior, seasonal territory-acquisition and pace of life.
RESULTS: We found that generally, the profiles of testosterone and territorial
behavior were similar across latitudes. African stonechats with a slow pace of
life had equally high peak testosterone concentrations and responded as
aggressively to an intruder as European stonechats with a fast pace of life.
However, song performance at the beginning of the breeding season was lower in
African than in European stonechats. The differences in song performance were not
associated with variation in testosterone levels between tropical and temperate
stonechats. CONCLUSIONS: The results suggest a very similar role for testosterone
as a mediator of high intensity territorial aggression during the fertile period
of females in tropical and temperate stonechats, which all are highly seasonal,
locally synchronous breeders. A potential explanation may be high risk of extra
pair copulations which has been associated with synchronous breeding.
Interestingly, an association was not consistent for song performance. Our data
suggest that song performance can be disassociated from peak testosterone levels
depending on its role in breeding behavior. Despite similar testosterone levels,
European males, which early in the breeding season acquire territories and mates,
showed greater song performance than African stonechats, which maintain year
round territories and pair-bonds. Taken together, our study comparing related
taxa of old world songbirds suggests that short breeding seasons may be a major
selective force for high peak testosterone levels during breeding regardless of
latitude and pace of life, but that particular behaviors, in our case song, can
be uncoupled from peak testosterone levels.
PMID- 28412930
TI - Large-scale analysis of post-translational modifications in E. coli under glucose
limiting conditions.
AB - BACKGROUND: Post-translational modification (PTM) of proteins is central to many
cellular processes across all domains of life, but despite decades of study and a
wealth of genomic and proteomic data the biological function of many PTMs remains
unknown. This is especially true for prokaryotic PTM systems, many of which have
only recently been recognized and studied in depth. It is increasingly apparent
that a deep sampling of abundance across a wide range of environmental stresses,
growth conditions, and PTM types, rather than simply cataloging targets for a
handful of modifications, is critical to understanding the complex pathways that
govern PTM deposition and downstream effects. RESULTS: We utilized a deeply
sampled dataset of MS/MS proteomic analysis covering 9 timepoints spanning the
Escherichia coli growth cycle and an unbiased PTM search strategy to construct a
temporal map of abundance for all PTMs within a 400 Da window of mass shifts.
Using this map, we are able to identify novel targets and temporal patterns for N
terminal N alpha acetylation, C-terminal glutamylation, and asparagine
deamidation. Furthermore, we identify a possible relationship between N-terminal
N alpha acetylation and regulation of protein degradation in stationary phase,
pointing to a previously unrecognized biological function for this poorly
understood PTM. CONCLUSIONS: Unbiased detection of PTM in MS/MS proteomics data
facilitates the discovery of novel modification types and previously unobserved
dynamic changes in modification across growth timepoints.
PMID- 28412931
TI - Prevalence of Escherichia coli O157:H7 in beef cattle at slaughter and beef
carcasses at retail shops in Ethiopia.
AB - BACKGROUND: There is paucity of information regarding the epidemiology of
Escherichia coli O157: H7 in developing countries. In this study, we investigated
the occurrence of E. coli O157: H7 associated with beef cattle at processing
plants and at retail shops in Ethiopia. METHODS: Various samples were collected
from beef cattle at slaughter/processing plants, carcass at retail shops and
humans at health centers. E. coli O157: H7 was isolated, identified and
characterized for antimicrobial resistance, using standard microbiological
methods. RESULTS: At the processing plants E. coli O157: H7 was detected in 1.89%
of fecal, 0.81% of intestinal mucosal swab, 0.54% of skin swab and 0.54% of
carcass internal swab samples. At retail shops it was detected in 0.8% of carcass
and 0.8% of cutting board swab samples, while all samples from utensils, hands
from workers, and fecal and stool samples were negative. All isolates were
resistant to Amoxicillin, moderately resistant to Cefoxitine and Nitrofurantoins
but susceptible to other antimicrobials tested. CONCLUSIONS: E. coli O157: H7
occurs at low prevalence in beef cattle, and the current sanitary dressing
procedures in the processing plants and storage conditions in the retail shops
are effective against E. coli O157: H7.
PMID- 28412932
TI - Isolation of enterococci, their antimicrobial susceptibility patterns and
associated factors among patients attending at the University of Gondar Teaching
Hospital.
AB - BACKGROUND: Enterococci become clinically important especially in immune
compromised patients and important causes of nosocomial infections. Data on the
prevalence, antimicrobial susceptibility patterns and associated factors of
enterococci are scarce in Ethiopia. METHODS: A hospital based cross-sectional
study was conducted at the University of Gondar Teaching Hospital from February
28, 2014 to May 1, 2014. Pretested structured questionnaire was used to collect
socio-demographic data and possible associated factors of enterococci infections.
Clinical samples including urine, blood, wound swabs and other body fluids from
patients requested by physician for culture and antimicrobial susceptibility test
during the study period were included. A total of 385 patients were included in
the study. Data were entered and analyzed using SPSS Version 20. P values <0.05
were considered as statistically significant. RESULT: The overall prevalence of
enterococci infection was 6.2% (24/385). The commonest sites of infections were
urinary tract followed by wound and blood. Among the 24 isolates, 33.3% (8/24)
were resistant to all tested antimicrobial agents. Forty one point 7 % (10/24) of
the enterococci isolates were vancomycin resistant enterococci (VRE). Moreover,
two third of the isolates were multidrug resistant (MDR) enterococci. In
multivariate analysis, duration of hospital stay for two days and more than two
days with infection rate 17/32 (53.1%), previous history of any antibiotics (AOR
= 9.13; [95% CI; 2.01-41.51] P = 0.00) and history of urinary catheterization
(AOR = 8.80; [95% CI; 1.70-45.64] P = 0.01) were associated with presence of
higher enterococci infections than their respective groups. CONCLUSION: The
prevalence of enterococci infections among patients with UTIs, wound infections
and sepsis were higher than the other infections. Multi drug resistant
enterococci including VRE were isolated from clinical samples in the study area.
Being hospitalized for >=48 h, having history of any antibiotic administration
and catheterization were associated factors for enterococci infections. Presence
of VRE indicates decreased antibiotic treatment options of multidrug resistant
enterococci. Therefore, efforts should be made to prevent enterococci infections
and emergency of multidrug resistant enterococci. Moreover, species
identification and antibiotic resistant in advanced and at large scale is
demanding.
PMID- 28412933
TI - Beyond quality of life: a cross sectional study on the mental health of patients
with chronic kidney disease undergoing dialysis and their caregivers.
AB - BACKGROUND: Patients with terminal chronic kidney disease (CKDT) requiring renal
replacement therapies (RRT) undergo important changes in living habits and
frequently need caregiving. These patients and their caregivers are risk groups
for the development of physical and psychological symptoms. This study aimed to
evaluate the prevalence of anxiety, depression, stress, fatigue, social support,
and quality of life in patients with CKD and their caregivers. METHOD: This cross
sectional study was conducted with 21 patients and their caregivers, from January
to September 2015. We included patients aged over 18 years, with at least 6
months on dialysis treatment, and caregivers who were family members. The
participants' social, demographic, clinical, laboratory, and psychological
variables were evaluated. A descriptive analysis and an examination of the
association between patients and caregivers were performed. RESULTS: Among
patients, we observed that 38.1% had symptoms that indicated anxiety and
depression. The average score for practical social support was 3.15 +/- 0.769 and
that for emotional social support was 3.16 +/- 0.79. As for fatigue, 14.3% of
patients reported being 'extremely tired' and 14.3% reported that they engaged in
all the activities they usually performed before the illness. Further, 57.1%
presented stress, and of these, 66.7% were at the resistance stage, with
predominance of psychological symptoms in 60.0%. The quality of life domain in
terms of functional capacity (FC) presented a correlation with haemoglobin level
(r = 0.581, p = 0.006) and non-anaemic patients presented better FC. Among
caregivers, we observed symptoms that indicated anxiety and depression in 33.3%
of the sample. Caregivers exhibited an average score of 2.88 +/- 0.77 for
practical social support and 3.0 +/- 0.72 for emotional social support. Further,
14.3% reported being 'extremely tired' and 28.8% reported that they engaged in
all activities that they usually performed before the patient's illness. When
comparing the two groups (patients vs. caregivers), we observed that they
presented similar results for the presence of anxiety, depression, and fatigue.
Caregivers received less social support than patients did. Both groups presented
similar predominance of stress levels; however, patients presented more
predominance of psychological symptoms. With reference to quality of life,
patients and caregivers presented similar results on the social aspects,
vitality, mental health, and mental domains. CONCLUSION: The mental health
characteristics of patients and caregivers were similar, and within the context
of dialysis for renal disease, both must undergo specific interventions.
PMID- 28412934
TI - Karyotype diversity and chromosomal organization of repetitive DNA in Tityus
obscurus (Scorpiones, Buthidae).
AB - BACKGROUND: Holocentric chromosomes occur in approximately 750 species of
eukaryotes. Among them, the genus Tityus (Scorpiones, Buthidae) has a labile
karyotype that shows complex multivalent associations during male meiosis. Thus,
taking advantage of the excellent model provided by the Buthidae scorpions, here
we analyzed the chromosomal distribution of several repetitive DNA classes on the
holocentric chromosomes of different populations of the species Tityus obscurus
Gervais, 1843, highlighting their involvement in the karyotypic differences found
among them. RESULTS: This species shows inter- and intrapopulational karyotype
variation, with seven distinct cytotypes: A (2n = 16), B (2n = 14), C (2n = 13),
D (2n = 13), E (2n = 12), F (2n = 12) and G (2n = 11). Furthermore, exhibits
achiasmatic male meiosis and lacks heteromorphic sex chromosomes. Trivalent and
quadrivalent meiotic associations were found in some cytotypes. In them, 45S
rDNAs were found in the terminal portions of two pairs, while TTAGG repeats were
found only at the end of the chromosomes. In the cytotype A (2n = 16), the U2
snRNA gene mapped to pair 1, while the H3 histone cluster and C 0 t-1 DNA
fraction was terminally distributed on all pairs. Mariner transposons were found
throughout the chromosomes, with the exception of one individual of cytotype A
(2n = 16), in which it was concentrated in heterochromatic regions. CONCLUSIONS:
Chromosomal variability found in T. obscurus are due to rearrangements of the
type fusion/fission and reciprocal translocations in heterozygous. These
karyotype differences follow a geographical pattern and may be contributing to
reproductive isolation between populations analyzed. Our results also demonstrate
high mobility of histone H3 genes. In contrast, other multigene families (45S
rDNA and U2 snRNA) have conserved distribution among individuals. The
accumulation of repetitive sequences in distal regions of T. obscurus
chromosomes, suggests that end of chromosome are not covered by the kinetochore.
PMID- 28412935
TI - Fitness costs of symbiont switching using entomopathogenic nematodes as a model.
AB - BACKGROUND: Steinernematid nematodes form obligate symbioses with bacteria from
the genus Xenorhabdus. Together Steinernema nematodes and their bacterial
symbionts successfully infect, kill, utilize, and exit their insect hosts. During
this process the nematodes and bacteria disassociate requiring them to re
associate before emerging from the host. This interaction can be complicated when
two different nematodes co-infect an insect host. RESULTS: Non-cognate nematode
bacteria pairings result in reductions for multiple measures of success,
including total progeny production and virulence. Additionally, nematode
infective juveniles carry fewer bacterial cells when colonized by a non-cognate
symbiont. Finally, we show that Steinernema nematodes can distinguish
heterospecific and some conspecific non-cognate symbionts in behavioral choice
assays. CONCLUSIONS: Steinernema-Xenorhabdus symbioses are tightly governed by
partner recognition and fidelity. Association with non-cognates resulted in
decreased fitness, virulence, and bacterial carriage of the nematode-bacterial
pairings. Entomopathogenic nematodes and their bacterial symbionts are a useful,
tractable, and reliable model for testing hypotheses regarding the evolution,
maintenance, persistence, and fate of mutualisms.
PMID- 28412936
TI - 1H-NMR analysis of feces: new possibilities in the helminthes infections
research.
AB - BACKGROUND: Analysis of the stool samples is an essential part of routine
diagnostics of the helminthes infections. However, the standard methods such Kato
and Kato-Katz utilize only a fraction of the information available. Here we
present a method based on the nuclear magnetic resonance spectroscopy (NMR) which
could be auxiliary to the standard procedures by evaluating the complex metabolic
profiles (or phenotypes) of the samples. METHOD: The samples were collected over
the period of June-July 2015, frozen at -20 degrees C at the site of collection
and transferred within four hours for the permanent storage at -80 degrees C.
Fecal metabolites were extracted by mixing aliquots of about 100 mg thawed stool
material with 0.5 mL phosphate buffer saline, followed by the homogenization and
centrifugations steps. All NMR data were recorded using a Bruker 600 MHz AVANCE
II spectrometer equipped with a 5 mm triple resonance inverse cryoprobe and a z
gradient system. RESULTS: Here we report an optimized method for NMR based
metabolic profiling/phenotyping of the stools samples. Overall, 62 metabolites
were annotated in the pool sample using the 2D NMR spectra and the Bruker
Biorefcode database. The compounds cover a wide range of the metabolome including
amino acids and their derivatives, short chain fatty acids (SCFAs), carboxylic
acids and their derivatives, amines, carbohydrates, purines, alcohols and others.
An exploratory analysis of the metabolic profiles reveals no strong trends
associated with the infection status of the patients. However, using the
penalized regression as a variable selection method we succeeded in finding a
subset of eleven variables which enables to discriminate the patients on basis of
their infections status. CONCLUSIONS: A simple method for metabolic
profiling/phenotyping of the stools samples is reported and tested on a pilot
opisthorchiasis cohort. To our knowledge this is the first report of a NMR-based
feces analysis in the context of the helminthic infections.
PMID- 28412937
TI - Understanding relevance of health research: considerations in the context of
research impact assessment.
AB - BACKGROUND: With massive investment in health-related research, above and beyond
investments in the management and delivery of healthcare and public health
services, there has been increasing focus on the impact of health research to
explore and explain the consequences of these investments and inform strategic
planning. Relevance is reflected by increased attention to the usability and
impact of health research, with research funders increasingly engaging in
relevance assessment as an input to decision processes. Yet, it is unclear
whether relevance is a synonym for or predictor of impact, a necessary condition
or stage in achieving it, or a distinct aim of the research enterprise. The main
aim of this paper is to improve our understanding of research relevance, with
specific objectives to (1) unpack research relevance from both theoretical and
practical perspectives, and (2) outline key considerations for its assessment.
APPROACH: Our approach involved the scholarly strategy of review and reflection.
We prepared a draft paper based on an exploratory review of literature from
various fields, and gained from detailed and insightful analysis and critique at
a roundtable discussion with a group of key health research stakeholders. We also
solicited review and feedback from a small sample of expert reviewers.
CONCLUSIONS: Research relevance seems increasingly important in justifying
research investments and guiding strategic research planning. However,
consideration of relevance has been largely tacit in the health research
community, often depending on unexplained interpretations of value, fit and
potential for impact. While research relevance seems a necessary condition for
impact - a process or component of efforts to make rigorous research usable -
ultimately, relevance stands apart from research impact. Careful and explicit
consideration of research relevance is vital to gauge the overall value and
impact of a wide range of individual and collective research efforts and
investments. To improve understanding, this paper outlines four key
considerations, including how research relevance assessments (1) orientate to,
capture and compare research versus non-research sources, (2) consider both
instrumental versus non-instrumental uses of research, (3) accommodate dynamic
temporal-shifting perspectives on research, and (4) align with an intersubjective
understanding of relevance.
PMID- 28412939
TI - Diagnostic validity of the STRATIFY and Downton instruments for evaluating the
risk of falls by hospitalised acute-care patients: a multicentre longitudinal
study.
AB - BACKGROUND: Falls are major adverse events in hospitals. The appropriateness of
using risk assessment instruments for falls in hospitals has recently been
questioned, although the research performed in this respect presents some
methodological shortcomings. The purpose of the present study is to evaluate the
accuracy of the Downton and STRATIFY instruments to determine the risk of falls
and to predict their incidence in acute care hospitals in the public health
system in Andalusia (Spain). METHODS: A longitudinal, multicentre prospective
study was made of a cohort of patients recruited between May 2014 and March 2016.
The risk of falls was assessed using each of the above instruments during the
first 24 h after hospital admittance, with later re-evaluations every 72 h until
discharge. Descriptive statistics were obtained, bivariate and multivariate
analysis were performed. The diagnostic validity of the process was assessed by
calculations of sensitivity, specificity, positive and negative predictive values
and ratios of positive and negative likelihood. ROC curve analysis was performed
for both instruments. RESULTS: For this study, 1247 patients were recruited, of
whom 977 completed all the follow-up assessments. Twenty-three of these patients
(2.35%) suffered 24 falls. ROC curve analysis showed that the optimal cut-off
point for each assessment instrument was below that described by the authors: AUC
STRATIFY = 0.69 (95% CI: 0.57-0.8); AUC Downton = 0.6 (95% CI: 0.48-0.72). With a
cut-off point of 1, the sensitivity of STRATIFY was 47.6% and its specificity,
85%. With a cut-off point of 2, Downton presented a sensitivity of 66.7% and a
specificity of 55.3%. CONCLUSIONS: The Downton and STRATIFY falls risk assessment
instruments presented little utility as means of detecting the risk of falls
among a sample of adult patients admitted to acute care hospitals. Fall
prevention in hospitals should be based on the study of individual risk factors.
PMID- 28412938
TI - Broad and flexible stable isotope niches in invasive non-native Rattus spp. in
anthropogenic and natural habitats of central eastern Madagascar.
AB - BACKGROUND: Rodents of the genus Rattus are among the most pervasive and
successful invasive species, causing major vicissitudes in native ecological
communities. A broad and flexible generalist diet has been suggested as key to
the invasion success of Rattus spp. Here, we use an indirect approach to better
understand foraging niche width, plasticity, and overlap within and between
introduced Rattus spp. in anthropogenic habitats and natural humid forests of
Madagascar. RESULTS: Based on stable carbon and nitrogen isotope values measured
in hair samples of 589 individual rodents, we found that Rattus rattus had an
extremely wide foraging niche, encompassing the isotopic space covered by a
complete endemic forest-dwelling Malagasy small mammal community. Comparisons of
Bayesian standard ellipses, as well as (multivariate) mixed-modeling analyses,
revealed that the stable isotope niche of R. rattus tended to change seasonally
and differed between natural forests and anthropogenic habitats, indicating
plasticity in feeding niches. In co-occurrence, R. rattus and Rattus norvegicus
partitioned feeding niches. Isotopic mismatch of signatures of individual R.
rattus and the habitat in which they were captured, indicate frequent dispersal
movements for this species between natural forest and anthropogenic habitats.
CONCLUSIONS: Since R. rattus are known to transmit a number of zoonoses,
potentially affecting communities of endemic small mammals, as well as humans,
these movements presumably increase transmission potential. Our results suggest
that due to their generalist diet and potential movement between natural forest
and anthropogenic habitats, Rattus spp. might affect native forest-dependent
Malagasy rodents as competitors, predators, and disease vectors. The combination
of these effects helps explain the invasion success of Rattus spp. and the
detrimental effects of this genus on the endemic Malagasy rodent fauna.
PMID- 28412940
TI - Absence of the dermatan sulfate chain of decorin does not affect mouse
development.
AB - BACKGROUND: In vitro studies suggest that the multiple functions of decorin are
related to both its core protein and its dermatan sulfate chain. To determine the
contribution of the dermatan sulfate chain to the functional properties of
decorin in vivo, a mutant mouse whose decorin lacked a dermatan sulfate chain was
generated. RESULTS: Homozygous mice expressing only the decorin core protein
developed and grew in a similar manner to wild type mice. In both embryonic and
postnatal mice, all connective tissues studied, including cartilage, skin and
cornea, appeared to be normal upon histological examination, and their collagen
fibrils were of normal diameter and organization. In addition, abdominal skin
wounds healed in an identical manner in the mutant and wild type mice.
CONCLUSIONS: The absence of a dermatan sulfate chain on decorin does not appear
to overtly influence its functional properties in vivo.
PMID- 28412941
TI - Survival prediction in Amyotrophic lateral sclerosis based on MRI measures and
clinical characteristics.
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) a highly heterogeneous
neurodegenerative condition. Accurate diagnostic, monitoring and prognostic
biomarkers are urgently needed both for individualised patient care and clinical
trials. A multimodal magnetic resonance imaging study is presented, where MRI
measures of ALS-associated brain regions are utilised to predict 18-month
survival. METHODS: A total of 60 ALS patients and 69 healthy controls were
included in this study. 20% of the patient sample was utilised as an independent
validation sample. Surface-based morphometry and diffusion tensor white matter
parameters were used to identify anatomical patterns of neurodegeneration in 80%
of the patient sample compared to healthy controls. Binary logistic ridge
regressions were carried out to predict 18-month survival based on clinical
measures alone, MRI features, and a combination of clinical and MRI data.
Clinical indices included age at symptoms onset, site of disease onset,
diagnostic delay from first symptom to diagnosis, and physical disability (ALSFRS
r). MRI features included the average cortical thickness of the precentral and
paracentral gyri, the average fractional anisotropy, radial-, medial-, and axial
diffusivity of the superior and inferior corona radiata, internal capsule,
cerebral peduncles and the genu, body and splenium of the corpus callosum.
RESULTS: Clinical data alone had a survival prediction accuracy of 66.67%, with
62.50% sensitivity and 70.84% specificity. MRI data alone resulted in a
prediction accuracy of 77.08%, with 79.16% sensitivity and 75% specificity. The
combination of clinical and MRI measures led to a survival prediction accuracy of
79.17%, with 75% sensitivity and 83.34% specificity. CONCLUSION: Quantitative MRI
measures of ALS-specific brain regions enhance survival prediction in ALS and
should be incorporated in future clinical trial designs.
PMID- 28412942
TI - Breast cancer screening practices of African migrant women in Australia: a
descriptive cross-sectional study.
AB - BACKGROUND: Breast cancer is the most diagnosed cancer among women and a leading
cause of mortality and morbidity, globally. Breast cancer mortality can be
improved through routine cancer screening, yet migrant populations have lower
participation rates. While African migrants are among the fastest growing migrant
population in Australia, their breast cancer screening behaviour is under
studied. The aims of this study were to report breast cancer screening status of
African migrant women and factors associated with their breast cancer screening
behaviour in Australia. METHODS: A descriptive, cross-sectional approach was
utilised for this study. Two hundred and sixty four African migrant women aged 18
69 years and recruited from a number of organisations responded to a self
reported African version of the Breast Cancer Screening Beliefs Questionnaire
(BCSBQ). Main research variables are breast cancer screening practices and
demographic characteristics and total scores on each of the BCSBQ subscales.
Multivariable logistic regression analyses were performed to investigate the
impact of the demographic variables on the likelihood of women in the target age
range 50-74 years having screening practices as recommended. RESULTS: While most
of the participants heard of breast awareness (76.1%) and mammogram (85.2%), only
11.4% practised monthly breast awareness, whereas 65.9% had ever had a mammogram
as frequently as recommended. Age and employment were determining factors for
participating in mammogram. Significant different scores were found in the
"Practical barriers" between women at the target age who had and had not
performed breast awareness (80.4 versus 77.5, p-value = 0.002) and mammogram
(77.1 versus 70.3, p-value = 0.009) regularly as recommended. Moreover, attitudes
towards general health check-ups subscale scores were significantly higher in
women who had performed clinical breast examination as frequently as recommended
than those who had not. CONCLUSIONS: The research reveals that practical barriers
and attitudes towards general health check-ups are important factors to take into
account in determining African migrant women's participation in breast cancer
screening. Progress in reducing breast cancer deaths through early detection
needs to focus on attitudinal change among African migrants.
PMID- 28412943
TI - Generic care pathway for elderly patients in need of home care services after
discharge from hospital: a cluster randomised controlled trial.
AB - BACKGROUND: Improved discharge arrangements and targeted post-discharge follow-up
can reduce the risk of adverse events after hospital discharge for elderly
patients. Although more care is to shift from specialist to primary care, there
are few studies on post-discharge interventions run by primary care. A generic
care pathway, Patient Trajectory for Home-dwelling elders (PaTH) including
discharge arrangements and follow-up by primary care, was developed and
introduced in Central Norway Region in 2009, applying checklists at defined
stages in the patient trajectory. In a previous paper, we found that PaTH had
potential of improving follow-up in primary care. The aim of this study was to
establish the effect of PaTH-compared to usual care-for elderly in need of home
care services after discharge from hospital. METHODS: We did an unblinded,
cluster randomised controlled trial with 12 home care clusters. Outcomes were
measured at the patient level during a 12-month follow-up period for the
individual patient and analysed applying linear and logistic mixed models.
Primary outcomes were readmissions within 30 days and functional level assessed
by Nottingham extended ADL scale. Secondary outcomes were number and length of
inpatient hospital care and nursing home care, days at home, consultations with
the general practitioners (GPs), mortality and health related quality of life (SF
36). RESULTS: One-hundred and sixty-three patients were included in the PaTH
group (six clusters), and 141 patients received care as usual (six clusters). We
found no statistically significant differences between the groups for primary and
secondary outcomes except for more consultations with the GPs in PaTH group (p =
0.04). Adherence to the intervention was insufficient as only 36% of the patients
in the intervention group were assessed by at least three of the four main
checklists in PaTH, but this improved over time. CONCLUSIONS: Lack of adherence
to PaTH rendered the study inconclusive regarding the elderly's functional level,
number of readmissions after hospital discharge, and health care utilisation
except for more consultations with the GPs. A targeted exploration of
prerequisites for implementation is recommended in the pre-trial phase of complex
intervention studies. TRIAL REGISTRATION: Clinical Trials.gov NCT01107119 ,
retrospectively registered 2010.04.18.
PMID- 28412944
TI - Length of paediatric inpatient stay, socio-economic status and hospital
configuration: a retrospective cohort study.
AB - BACKGROUND: Variation in paediatric inpatient length of stay exists - whether
this is driven by differences in patient characteristics or health service
delivery is unclear. We will test the hypotheses that higher levels of
deprivation are associated with prolonged length of stay and that differences in
prolonged length of stay across 2 hospitals will be explained by demographic,
clinical and process factors. METHODS: This is a retrospective cohort study of
2889 children aged less than 16 years admitted from 1st April 2009 to 30th March
2010. Administrative data were used from two UK hospitals whose Accident and
Emergency (A&E) departments were paediatric and adult physician led respectively.
The main outcome was prolonged length of stay defined as greater than or equal to
the mean (1.8 days). Sensitivity analyses defined prolonged length of stay as
greater than the median (1 day). Demographic, clinical and process
characteristics were examined. Socio-economic position was measured by Income
Deprivation Affecting Children Index. Multivariable logistic and linear
regression analyses were performed. RESULTS: We did not find a consistent
association between length of stay and socio-economic position, using a variety
of definitions of length of stay. In contrast, adjusted for age, gender, socio
economic position, ethnicity, final diagnosis, number of hospital admissions,
source of admission, and timing of admission, admission to the adult led A&E
hospital was more strongly associated with prolonged length of stay (Odds Ratio
1.41, 95% Confidence Interval 1.16, 1.71). CONCLUSION: Local variation in
paediatric inpatient length of stay was not explained by demographic, clinical or
process factors, but could have been due to residual confounding by medical
complexity. Length of stay was not consistently associated with socio-economic
position suggesting that length of stay is a function of health service not the
determinants of health. Analyses of these types of data would be strengthened by
measures of complexity and adverse events.
PMID- 28412945
TI - Multimorbidity associated with functional independence among community-dwelling
older people: a cross-sectional study in Southern China.
AB - BACKGROUND: Multimorbidity, the coexistence of two or more chronic diseases, is
common in older adults. And it may lead to many adverse health outcomes, such as
disability. However, data on multimorbidity and its relationship with functional
independence are scarce in Asian countries. Therefore, this study aims to
investigate the relationship between multimorbidity and functional status among
older people in China. METHODS: Based on a cross-sectional survey, the
information regarding 2705 older adults, who were of at least 60 years of age,
was collected through interviews and analyzed. To assess functional status, we
used the Functional Independence Measure (FIM). Exploratory factor analysis was
performed to assess correlations among chronic diseases. Several logistic
regression models were run in the study. RESULTS: The presence of two or more
chronic conditions and the number of multimorbidity group overlaps were
independent risk factors for the loss of functional independence in older adults.
Hypertension and chronic pain, emerged as the most prevalent multimorbidity pair,
was significantly associated with functional independence (OR = 1.64, 95% CI =
1.25-2.16), followed by the co-occurrence of hypertension and heart diseases with
a lower prevalence but a higher OR compared with the former pair (OR = 1.72, 95%
CI = 1.15-2.58). Of the five multimorbidity groups used for factor analysis, the
bones and pain group (OR = 1.47, 95% CI = 1.23-1.77) and the cardiometabolic
group (OR = 1.34, 95% CI = 1.13-1.59) were both found to be significantly
correlated with lower functional independence. CONCLUSIONS: Multimorbidity was
common among older people in Southern China. Studying the relationship between
multimorbidity and functional status could be useful to find potential
correlations among chronic diseases. Additionally, it may also be meaningful to
identify multimorbidity combinations, posing an increased risk of loss of
functional independence, and further improve functional status in older adults
with comorbidities.
PMID- 28412946
TI - Big data and data repurposing - using existing data to answer new questions in
vascular dementia research.
AB - INTRODUCTION: Traditional approaches to clinical research have, as yet, failed to
provide effective treatments for vascular dementia (VaD). Novel approaches to
collation and synthesis of data may allow for time and cost efficient hypothesis
generating and testing. These approaches may have particular utility in helping
us understand and treat a complex condition such as VaD. METHODS: We present an
overview of new uses for existing data to progress VaD research. The overview is
the result of consultation with various stakeholders, focused literature review
and learning from the group's experience of successful approaches to data
repurposing. In particular, we benefitted from the expert discussion and input of
delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16
18th October 2015). RESULTS: We agreed on key areas that could be of relevance to
VaD research: systematic review of existing studies; individual patient level
analyses of existing trials and cohorts and linking electronic health record data
to other datasets. We illustrated each theme with a case-study of an existing
project that has utilised this approach. CONCLUSIONS: There are many
opportunities for the VaD research community to make better use of existing data.
The volume of potentially available data is increasing and the opportunities for
using these resources to progress the VaD research agenda are exciting. Of
course, these approaches come with inherent limitations and biases, as bigger
datasets are not necessarily better datasets and maintaining rigour and critical
analysis will be key to optimising data use.
PMID- 28412947
TI - Report of the first clinical case of intestinal trichomoniasis caused by
Tritrichomonas foetus in a cat with chronic diarrhoea in Brazil.
AB - BACKGROUND: Tritrichomonas foetus is an emergent and important enteric pathogen
of cats, which causes prolonged diarrhoea in cats. CASE PRESENTATION: This study
describes a T. foetus infection in a seven-month-old, entire male domestic
shorthair kitten with a six-month history of persistent large intestinal
diarrhoea, faecal incontinence, prostration, apathy and weight loss. Parasites
were microscopically observed and confirmed by PCR and DNA sequencing. Molecular
analyses were carried out comparing the sequence obtained in this study with T.
foetus and T. suis. Retrieved from GenBank. After treatment with ronidazole, the
cat showed resolution of clinical signs. CONCLUSIONS: This is the first clinical
case of T. foetus infection in a chronic diarrheic cat in Brazil and South
America, confirming the presence of this pathogen in this part of the world and
highlighting the importance of this protozoa being considered in the differential
diagnosis of cats presenting diarrhoea of the large intestine. Our case report
enriches our knowledge on the geographical distribution of T. foetus in cats in
Brazil and provides further understanding of the clinical significance of feline
intestinal trichomoniasis in this country.
PMID- 28412948
TI - A computerized tablet system for evaluating treatment of essential tremor by
magnetic resonance guided focused ultrasound.
AB - BACKGROUND: Transcranial magnetic resonance guided focused ultrasound is an
emerging technology under evaluation for treatment of essential tremor, a
prevalent movement disorder. A qualitative evaluation is performed by a clinician
periodically during the procedure to maximize treatment effects and minimize
adverse effects. The present work demonstrates a magnetic resonance-compatible
method to enable more precise, quantitative measurement of tremor severity.
METHODS: Tremor severity was measured in 12 patients pre-, post-, and intra
operatively, using a magnetic resonance-compatible tablet and a computerized
adaptation of drawing tasks from the widely-used Fahn-Tolosa-Marin Tremor Rating
Scale. Tremor metrics based on spectral analysis were calculated for each drawing
and compared using Wilcoxon signed rank tests. RESULTS: Tremor metrics in the
dominant (treated) hand were significantly and consistently lower post
operatively compared to pre-operatively, but there was no significant difference
in the non-dominant (untreated) hand, as expected. Intra-operative metrics were
intermediate between pre- and post-operative metrics. CONCLUSIONS: Use of the
tablet for quantitative tremor measurement was demonstrated pre-, post-, and
intra-operatively during treatment of essential tremor, complementing standard
qualitative assessment. With additional work, the system has potential to add
objectivity to clinical trials and to aid treatment decision-making by providing
a metric for optimization during the procedure, which may eventually lead to more
optimal treatment. Enhancements and further studies are suggested, and extensions
to fMRI studies of essential tremor and Parkinson's disease are also likely.
PMID- 28412949
TI - Skin whitening among Cameroonian female university students: knowledge,
attitudes, practices and motivations.
AB - BACKGROUND: Lack of data on skin whitening (SW) among Cameroonian female
university students prompted us to undertake the present study which aimed at
assessing the knowledge, attitudes, practices and motivations of female
university students vis-a-vis SW. METHODS: This was a cross-sectional study
conducted from January to April 2013 in 4 university campuses of Yaounde,
Cameroon. Any female student regularly registered in one of the study sites, who
was present at the campus when the investigator visited and volunteered to
participate in the study was enrolled. RESULTS: Overall, we recruited 620 female
students, their ages ranging from 16 to 46 years with a mean of 21.3 +/- 2.9
years. Only 87 participants (14%) found that SW was a good practice. One hundred
and sixty nine respondents (27.3%) were currently practicing SW with no age
difference when compared to their counterparts (p = 0.09). The desire to have a
uniform body skin color was the prevailing reason motivating the practice of SW
(39.1%), followed by the need to have a soft skin (29%). Assessment of levels of
knowledge regarding advantages of the black skin and deleterious effects of SW
showed excellent scores (>=75% of good answers) only in 6.1 and 0.5% of cases
respectively, with no difference between those practicing SW or not (all p values
> 0.05). CONCLUSION: The practice of SW is common among Cameroonian female
university students who should therefore be educated on the advantages of the
black skin and the harmful effects of SW.
PMID- 28412950
TI - Prevalence, withdrawal symptoms and associated factors of khat chewing among
students at Jimma University in Ethiopia.
AB - BACKGROUND: Recently, khat chewing has become a common practice among high
school, college, and university students. Regular khat chewing is thought to be a
predisposing factor for different physical and mental health problems. It can
lead to absenteeism from work and classes. In Ethiopia, to our knowledge no
published study has investigated khat withdrawal symptoms. Therefore, this study
was conducted to determine the prevalence, withdrawal symptoms, and associated
factors of khat chewing among regular undergraduate students on the main campus
of Jimma University in Ethiopia. METHODS: The institution-based, cross-sectional
study was conducted in January 2016. Data were collected from 651 main campus
regular undergraduate students with a structured, self-administered
questionnaire, entered into Epidata 3.1 and exported to SPSS version 20 for
Windows. Bivariate and multivariate logistic regressions were used to explore
associations and identify variables independently associated with khat chewing.
RESULTS: The study found that the lifetime and current prevalence of khat chewing
among students were 26.3% (95% CI: 24.3, 28.3) and 23.9% (95% CI: 21.94, 25.86),
respectively. About 25.7% of students started chewing after joining university,
and 60.5% of these students started during their first year. The main reason
given for starting khat chewing was for study purposes (54.6%), followed by
socialization purposes (42.3%). Among current khat chewers, 72.9% reported that
they had chewed khat for 1 year or more and 68.2% reported that they had
experienced various withdrawal symptoms. The most frequently reported withdrawal
symptoms were feeling depressed, craving, and feeling fatigued. Being male,
attending a place of worship daily/2-3 times per week, cannabis use, smoking
cigarettes, and having family members currently chewing khat were independently
associated with khat chewing. CONCLUSIONS: This study found that large numbers of
university students were currently chewing khat. In this study withdrawal
symptoms and factors that significantly affect khat chewing were identified.
Besides it gave new ideas regarding khat withdrawal symptoms in Ethiopia. It
serves as a critical role of providing information to form rational foundation
for public health policy, prevention and planning to bring change in contributing
factors for Khat chewing. The finding will be serving as base line information
for further study.
PMID- 28412951
TI - Understanding discharge communication behaviours in a pediatric emergency care
context: a mixed methods observation study protocol.
AB - BACKGROUND: One of the most important transitions in the continuum of care for
children is discharge to home. Optimal discharge communication between healthcare
providers and caregivers (e.g., parents or other guardians) who present to the
emergency department (ED) with their children is not well understood. The lack of
policies and considerable variation in practice regarding discharge communication
in pediatric EDs pose a quality and safety risk for children and their parents.
METHODS: The aim of this mixed methods study is to better understand the process
and structure of discharge communication in a pediatric ED context to contribute
to the design and development of discharge communication interventions. We will
use surveys, administrative data and real-time video observation to characterize
discharge communication for six common illness presentations in a pediatric ED:
(1) asthma, (2) bronchiolitis, (3) abdominal pain, (4) fever, (5) diarrhea and
vomiting, and (6) minor head injury. Participants will be recruited from one of
two urban pediatric EDs in Canada. Video recordings will be analyzed using
Observer XT. We will use logistic regression to identify potential demographic
and visit characteristic cofounders and multivariate logistic regression to
examine association between verbal and non-verbal behaviours and parent recall
and comprehension. DISCUSSION: Video recording of discharge communication will
provide an opportunity to capture important data such as temporality, sequence
and non-verbal behaviours that might influence the communication process. Given
the importance of better characterizing discharge communication to identify
potential barriers and enablers, we anticipate that the findings from this study
will contribute to the development of more effective discharge communication
policies and interventions.
PMID- 28412952
TI - Rayleigh-maximum-likelihood bilateral filter for ultrasound image enhancement.
AB - BACKGROUND: Ultrasound imaging plays an important role in computer diagnosis
since it is non-invasive and cost-effective. However, ultrasound images are
inevitably contaminated by noise and speckle during acquisition. Noise and
speckle directly impact the physician to interpret the images and decrease the
accuracy in clinical diagnosis. Denoising method is an important component to
enhance the quality of ultrasound images; however, several limitations discourage
the results because current denoising methods can remove noise while ignoring the
statistical characteristics of speckle and thus undermining the effectiveness of
despeckling, or vice versa. In addition, most existing algorithms do not identify
noise, speckle or edge before removing noise or speckle, and thus they reduce
noise and speckle while blurring edge details. Therefore, it is a challenging
issue for the traditional methods to effectively remove noise and speckle in
ultrasound images while preserving edge details. METHODS: To overcome the above
mentioned limitations, a novel method, called Rayleigh-maximum-likelihood
switching bilateral filter (RSBF) is proposed to enhance ultrasound images by two
steps: noise, speckle and edge detection followed by filtering. Firstly, a sorted
quadrant median vector scheme is utilized to calculate the reference median in a
filtering window in comparison with the central pixel to classify the target
pixel as noise, speckle or noise-free. Subsequently, the noise is removed by a
bilateral filter and the speckle is suppressed by a Rayleigh-maximum-likelihood
filter while the noise-free pixels are kept unchanged. To quantitatively evaluate
the performance of the proposed method, synthetic ultrasound images contaminated
by speckle are simulated by using the speckle model that is subjected to Rayleigh
distribution. Thereafter, the corrupted synthetic images are generated by the
original image multiplied with the Rayleigh distributed speckle of various signal
to noise ratio (SNR) levels and added with Gaussian distributed noise. Meanwhile
clinical breast ultrasound images are used to visually evaluate the effectiveness
of the method. To examine the performance, comparison tests between the proposed
RSBF and six state-of-the-art methods for ultrasound speckle removal are
performed on simulated ultrasound images with various noise and speckle levels.
RESULTS: The results of the proposed RSBF are satisfying since the Gaussian noise
and the Rayleigh speckle are greatly suppressed. The proposed method can improve
the SNRs of the enhanced images to nearly 15 and 13 dB compared with images
corrupted by speckle as well as images contaminated by speckle and noise under
various SNR levels, respectively. The RSBF is effective in enhancing edge while
smoothing the speckle and noise in clinical ultrasound images. In the comparison
experiments, the proposed method demonstrates its superiority in accuracy and
robustness for denoising and edge preserving under various levels of noise and
speckle in terms of visual quality as well as numeric metrics, such as peak
signal to noise ratio, SNR and root mean squared error. CONCLUSIONS: The
experimental results show that the proposed method is effective for removing the
speckle and the background noise in ultrasound images. The main reason is that it
performs a "detect and replace" two-step mechanism. The advantages of the
proposed RBSF lie in two aspects. Firstly, each central pixel is classified as
noise, speckle or noise-free texture according to the absolute difference between
the target pixel and the reference median. Subsequently, the Rayleigh-maximum
likelihood filter and the bilateral filter are switched to eliminate speckle and
noise, respectively, while the noise-free pixels are unaltered. Therefore, it is
implemented with better accuracy and robustness than the traditional methods.
Generally, these traits declare that the proposed RSBF would have significant
clinical application.
PMID- 28412953
TI - Quantification of task-dependent cortical activation evoked by robotic continuous
wrist joint manipulation in chronic hemiparetic stroke.
AB - BACKGROUND: Cortical damage after stroke can drastically impair sensory and motor
function of the upper limb, affecting the execution of activities of daily living
and quality of life. Motor impairment after stroke has been thoroughly studied,
however sensory impairment and its relation to movement control has received less
attention. Integrity of the somatosensory system is essential for feedback
control of human movement, and compromised integrity due to stroke has been
linked to sensory impairment. METHODS: The goal of this study is to assess the
integrity of the somatosensory system in individuals with chronic hemiparetic
stroke with different levels of sensory impairment, through a combination of
robotic joint manipulation and high-density electroencephalogram (EEG). A robotic
wrist manipulator applied continuous periodic disturbances to the affected limb,
providing somatosensory (proprioceptive and tactile) stimulation while
challenging task execution. The integrity of the somatosensory system was
evaluated during passive and active tasks, defined as 'relaxed wrist' and
'maintaining 20% maximum wrist flexion', respectively. The evoked cortical
responses in the EEG were quantified using the power in the averaged responses
and their signal-to-noise ratio. RESULTS: Thirty individuals with chronic
hemiparetic stroke and ten unimpaired individuals without stroke participated in
this study. Participants with stroke were classified as having severe, mild, or
no sensory impairment, based on the Erasmus modification of the Nottingham
Sensory Assessment. Under passive conditions, wrist manipulation resulted in
contralateral cortical responses in unimpaired and chronic stroke participants
with mild and no sensory impairment. In participants with severe sensory
impairment the cortical responses were strongly reduced in amplitude, which
related to anatomical damage. Under active conditions, participants with mild
sensory impairment showed reduced responses compared to the passive condition,
whereas unimpaired and chronic stroke participants without sensory impairment did
not show this reduction. CONCLUSIONS: Robotic continuous joint manipulation
allows studying somatosensory cortical evoked responses during the execution of
meaningful upper limb control tasks. Using such an approach it is possible to
quantitatively assess the integrity of sensory pathways; in the context of
movement control this provides additional information required to develop more
effective neurorehabilitation therapies.
PMID- 28412954
TI - Does a quality improvement campaign accelerate take-up of new evidence? A ten
state cluster-randomized controlled trial of the IHI's Project JOINTS.
AB - BACKGROUND: A decade ago, the Institute for Healthcare Improvement pioneered a
quality improvement (QI) campaign, leveraging organizational and personal social
networks to disseminate new practices. There have been few rigorous studies of
the QI campaign approach. METHODS: Project JOINTS (Joining Organizations IN
Tackling SSIs) engaged a network of state-based organizations and professionals
in a 6-month QI campaign promoting adherence to three new evidence-based
practices known to reduce the risk of infection after joint replacement. We
conducted a cluster-randomized trial including ten states (five campaign states
and five non-campaign states) with 188 hospitals providing joint replacement to
Medicare. We measured adherence to the evidence-based practices before and after
the campaign using a survey of surgical staff and a difference-in-difference
design with multivariable adjustment to compare adherence to each of the relevant
practices and an all-or-none composite measure of the three new practices.
RESULTS: In the campaign states, there were statistically significant increases
in adherence to the three new evidence-based practices promoted by the campaign.
Compared to the non-campaign states, the relative increase in adherence to the
three new practices in the campaign states ranged between 1.9 and 15.9 percentage
points, but only one of these changes (pre-operative nasal screening for
Staphylococcus aureus carriage and decolonization prior to surgery) was
statistically significant (p < 0.05). On the all-or-none composite measure,
adherence to all three evidence-based practices increased from 19.6 to 37.9% in
the campaign states, but declined slightly in the comparison states, yielding a
relative increase of 23 percentage points (p = 0.004). In the non-campaign
states, changes in adherence were not statistically significant. CONCLUSIONS:
Within 6 months, in a cluster-randomized trial, a multi-state campaign targeting
hospitals and professionals involved in surgical care and infection control was
associated with an increase in adherence to evidence-based practices that can
reduce surgical site infection.
PMID- 28412955
TI - Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung
cancer via NF-kappaB/Snail pathway.
AB - BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) play
key roles during multiple cancer processes, such as cell proliferation,
apoptosis, migration and invasion. The previous studies found that NKILA
interacted with and suppressed the nuclear translocation of NF-KappaB, which
influenced metastasis and prognosis in breast cancer. However the clinical
significance and biological role of NKILA in non-small cell lung cancer (NSCLC)
remains unknown. METHODS: We examined expression levels of NKILA in 106 pairs of
NSCLC tissues and cell lines. The expression level of NKILA after TGF-beta1
stimulation also was examined by qRT-PCR and validated by Chromatin
immunoprecipitation (ChIP). Gain-of-function and loss-of-function assays were
performed to examine the effect of NKILA on proliferation, migration and invasion
of NSCLC cells. RNA immunoprecipitation (RIP), western blot and rescue
experiments were carried out to reveal the interrelation between NKILA, NF-kappaB
and EMT signal pathway. RESULTS: The expression of NKILA was down-regulated in
NSCLC cancer tissues compared with matched adjacent noncancerous tissues, and
lower NKILA expression in tumor tissues were significantly correlated with lymph
node metastasis and advanced TNM stage. We found that the expression of NKILA was
mainly regulated by classical TGF-beta signal pathway in NSCLC cells rather than
NF-kappaB pathway reported in breast cancer. Gain and loss of function assays
found that NKILA inhibited migration, invasion and viability of NSCLC cells.
Mechanistic study showed that NKILA attenuated Snail expression via inhibiting
the phosphorylation of IkappaBalpha and NF-kappaB activation, subsequently
suppressed the expression of markers of epithelial-mesenchymal transition
process. CONCLUSIONS: The present study found that the expression of NKILA was
downregulated in tumor tissues of NSCLC, which improved the metastasis of NSCLC
patients. In vitro studies further clarified that the expression of NKILA was
regulated through classical TGF-beta signal pathway, which subsequently inhibited
migration and invasion of NSCLC cells through interfering NF-kappaB/Snail signal
pathway in NSCLC cells.
PMID- 28412956
TI - Management of suspected common bile duct stones on cholangiogram during same-stay
cholecystectomy for acute gallstone-related disease.
AB - BACKGROUND: Recent data have suggested that upfront cholecystectomy should be
performed even in the presence of moderately abnormal liver function tests
(LFTs). As a consequence, more common bile duct (CBD) stones are discovered on
intra-operative cholangiogram. We assessed the presentation and management of
such patients to refine their management plan. METHODS: Adult patients (>16
years) with an acute gallstone-related disease who had undergone same-stay
cholecystectomy from January 2013 to January 2015 were retrospectively assessed.
We excluded patients with pre-operative endoscopic CBD exploration. RESULTS:
Among the 612 patients with same-stay cholecystectomy, 399 patients were included
in the study, and 213 were excluded because of a pre-operative CBD exploration.
Fifty patients (12.5%) presented an image of CBD stone on the intra-operative
cholangiogram. Such patients were younger (47 vs. 55 years, P = .01) and less
likely to present with fever (1 vs. 11.7%, P = .04) or signs of cholecystitis on
ultrasound (66 vs. 83.7%, P = .003). Admission LFTs were higher in patients with
an image of a stone. Among the 50 patients with an image on cholangiogram, a
stone was confirmed in 26 (52%). Most patients (n = 32) underwent post-operative
assessment with endoscopic ultrasound (EUS). LFTs did not predict the presence of
a confirmed stone. However, the absence of contrast passage into the duodenum was
negatively associated with a confirmed stone (P = .08), and a filling defect was
positively associated with one (P = .11). Most confirmed stones were successfully
extracted by endoscopic retrograde cholangiopancreatogram (ERCP) (25/26, 96%),
except in one patient who needed a per-cutaneous approach because of duodenal
diverticuli. CONCLUSIONS: Same-stay cholecystectomy can (and should) be performed
even in the presence of moderately abnormal liver function tests. The
cholangiogram suspicion of a CBD stone is confirmed in only half of the patients
(more often in the presence of a filling defect, and less often with the absence
of contrast passage). All stones can be safely treated after surgery (most by
ERCP).
PMID- 28412957
TI - Pattern of drug use among preterm neonates: results from an Italian neonatal
intensive care unit.
AB - BACKGROUND: Drug use in preterm neonates admitted to Neonatal Intensive Care Unit
(NICU) has been investigated, so far, in terms of unauthorized or off-label use;
very little is known on the use of combinations of different active substances,
which is frequently required in this population (prophylaxis of infections,
treatment of concomitant diseases). The aim of this study was to describe the
most common patterns of drug use in an Italian NICU, focusing on those with
nephrotoxic potential. METHODS: Medical records of preterm neonates (<37 weeks of
gestational age) weighing less than 1,500 g at birth and admitted to an Italian
NICU were scrutinized in a 3-year retrospective investigation. Analysis included
drug exposure, duration of therapies, co-administration of drugs with potential
renal side effects; also daily protein supplement was calculated from parenteral
nutrition. RESULTS: A cohort of 159 preterm neonates was selected; 68 were born
weighing less than 1,000 g (extremely low birth weight infants, ELBW, Group A),
91 weighed between 1,000 and 1,500 g at birth (Group B). Compared to Group B,
neonates of Group A were more likely to receive pharmacological treatments: the
most used drugs were antibiotics (especially ampicillin and amikacin, p = .07 and
p < .001, respectively), antifungals (especially fluconazole, p < .001), and
diuretics (especially furosemide, p < .001). Analysis of co-administration of
drugs with potential nephrotoxicity showed ampicillin and amikacin as the most
reported combination (94.1% of Group A and 31.9% of Group B), the combination of
furosemide with antibacterials (ampicillin or amikacin) was also frequently
reported, with average period of combination shorter than 2 days. CONCLUSIONS:
ELBW infants were exposed to a higher number of drugs compared to other neonates
and were more likely to receive associations of drugs with nephrotoxic potential
(e.g. furosemide and amikacin), though only for short cycles. Further studies
should evaluate the safety profile (especially potential renal side effects)
related to most commonly used combinations.
PMID- 28412959
TI - Opportunities for developing therapies for rare genetic diseases: focus on gain
of-function and allostery.
AB - BACKGROUND: Advances in next generation sequencing technologies have
revolutionized our ability to discover the causes of rare genetic diseases.
However, developing treatments for these diseases remains challenging. In fact,
when we systematically analyze the US FDA orphan drug list, we find that only 8%
of rare diseases have an FDA-designated drug. Our approach leverages three
primary insights: first, diseases with gain-of-function mutations and late onset
are more likely to have drug options; second, drugs are more often inhibitors
than activators; and third, some disease-causing proteins can be rescued by
allosteric activators in diseases due to loss-of-function mutations. RESULTS: We
have developed a pipeline that combines natural language processing and human
curation to mine promising targets for drug development from the Online Mendelian
Inheritance in Man (OMIM) database. This pipeline targets diseases caused by well
characterized gain-of-function mutations or loss-of-function proteins with known
allosteric activators. Applying this pipeline across thousands of rare genetic
diseases, we discover 34 rare genetic diseases that are promising candidates for
drug development. CONCLUSION: Our analysis has revealed uneven coverage of rare
diseases in the current US FDA orphan drug space. Diseases with gain-of-function
mutations or loss-of-function mutations and known allosteric activators should be
prioritized for drug treatments.
PMID- 28412958
TI - Supporting parents in taking care of their infants admitted to a neonatal
intensive care unit: a prospective cohort pilot study.
AB - BACKGROUND: Family-Centred Care (FCC) is recognized as an important component of
all paediatric care, including neonatal care, although practical clinical
guidelines to support this care model are still needed in Italy. The
characteristics and services for families in Italian NICUs show a lack of
organization and participation. METHODS: The first aim was to compare
satisfaction and stress levels in two groups of parents: an FCC group and a non
FCC group (NFCC). The second aim was to evaluate body weight gain in the newborns
enrolled. This non-randomized, prospective cohort pilot study was conducted in a
single level III NICU at a hospital in Naples, Italy. A cohort of newborns in the
NICU, with their parents were enrolled between March 2014 and April 2015 and they
were divided into two groups: the FCC group (enrolled between October 2014 and
April 2015) remained in the NICU for 8 h a day with FCC model; the NFCC group
(enrolled between March 2014 and September 2014) was granted access to the NICU
for only 1 hour per day. At discharge, both parent groups completed the Parental
Stressor Scale (PSS)-NICU and a questionnaire to assess their satisfaction. In
addition, we compared scores from the mothers and fathers within and between
groups and the body weights of the newborns in the two groups at 60 days.
RESULTS: Parents participating in the FCC group were more satisfied and less
stressed than those in the NFCC group. Infants in the FCC group also showed
increased body weight after 60 days of hospital stay. CONCLUSIONS: Despite our
small population, we confirm that routine adoption of a procedure designed to
apply a FCC model can contribute to improving satisfaction and distress among
preterm infants' parents. Future multi-centre, randomized, controlled trials are
needed to confirm these findings.
PMID- 28412960
TI - A randomised controlled trial to determine the clinical and cost effectiveness of
thulium laser transurethral vaporesection of the prostate (ThuVARP) versus
transurethral resection of the prostate (TURP) in the National Health Service
(NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.
AB - BACKGROUND: Transurethral resection of the prostate (TURP) has been the standard
operation for benign prostatic obstruction (BPO) for 40 years, with approximately
25,000 procedures performed annually, and has remained largely unchanged. It is
generally a successful operation, but has well-documented risks for the patient.
Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and
resects the prostate using a surgical technique similar to TURP. The small amount
of study data currently available suggests that ThuVARP may have certain
advantages over TURP, including reduced blood loss and shorter hospital stay,
earlier return to normal activities, and shorter duration of catheterisation.
DESIGN: A multicentre, pragmatic, randomised, controlled, parallel-group trial of
ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable
for prostate surgery were randomised to receive either ThuVARP or TURP at four
university teaching hospitals, and three district general hospitals. The key aim
of the trial is to determine whether ThuVARP is equivalent to TURP judged on both
the patient-reported International Prostate Symptom Score (IPSS) and the maximum
urine flow rate (Qmax) at 12 months post-surgery. DISCUSSION: The general
population has an increased life expectancy. As men get older their prostates
enlarge, potentially causing BPO, which often requires surgery. Therefore, as the
population ages, more prostate operations are needed to relieve obstruction.
There is hence sustained interest in the condition and increasing need to find
safer techniques than TURP. Various laser techniques have become available but
none are widely used in the NHS because of lengthy training required for surgeons
or inferior performance on clinical outcomes. Promising initial evidence from one
RCT shows that ThuVARP has equivalent clinical effectiveness when compared to
TURP, as well as other potential advantages. As ThuVARP uses a technique similar
to that used in TURP, the learning curve is short, potentially making it also
very quickly generalisable. This randomised study is designed to provide the high
quality evidence, in an NHS setting, with a range of patient-reported, clinical
and cost-effectiveness outcomes, which will underpin and inform future NICE
guidance. TRIAL REGISTRATION: ISRCTN registry, ISRCTN00788389 . Registered on 20
September 2013.
PMID- 28412961
TI - Perventricular double-device closure of wide-spaced multi-hole perimembranous
ventricular septal defect.
AB - BACKGROUND: Device closure of a wide-spaced multi-hole PmVSD is difficult to
succeed in percutaneous approach. This study is to evaluate the feasibility,
safety and efficacy of perventricular device closure of wide-spaced multi-hole
PmVSD using a double-device implanting technique. METHODS: Sixteen patients with
wide-spaced multi-hole PmVSD underwent perventricular closure with two devices
through an inferior median sternotomy approach under transesophageal
echocardiographic guidance. The largest hole and its adjacent small holes were
occluded with an optimal-sized device. The far-away residual hole was occluded
with the other device using a probe-assisted delivery system. All patients were
followed up for a period of 1 to 4 years to determine the residual shunt,
atrioventricular block and the adjacent valvular function. RESULTS: The number of
the holes of the PmVSD was 2 to 4. The maximum distance between the holes was 5.0
to 10.0 mm (median, 6.4 mm). The diameter of the largest hole was 2.5 to 7.0 mm
(median, 3.6 mm). The success rate of double-device closure was 100%. Immediate
residual shunts were found in 6 patients (38%), and incomplete right bundle
branch block at discharge occurred in 3 cases (19%). Both complications decreased
to 6% at 1-year follow-up. Neither of them had a severe device-related
complication. CONCLUSIONS: Perventricular closure of a wide-spaced multi-hole
PmVSD using a double-device implanting technique is feasible, safe, and
efficacious. In multi-hole PmVSDs with the distance between the holes of more
than 5 mm, double-device implantation may achieve a complete occlusion.
PMID- 28412962
TI - Prospects for malaria control through manipulation of mosquito larval habitats
and olfactory-mediated behavioural responses using plant-derived compounds.
AB - Malaria presents an overwhelming public health challenge, particularly in sub
Saharan Africa where vector favourable conditions and poverty prevail,
potentiating the disease burden. Behavioural variability of malaria vectors poses
a great challenge to existing vector control programmes with insecticide
resistance already acquired to nearly all available chemical compounds. Thus,
approaches incorporating plant-derived compounds to manipulate semiochemical
mediated behaviours through disruption of mosquito olfactory sensory system have
considerably gained interests to interrupt malaria transmission cycle. The
combination of push-pull methods and larval control have the potential to reduce
malaria vector populations, thus minimising the risk of contracting malaria
especially in resource-constrained communities where access to synthetic
insecticides is a challenge. In this review, we have compiled information
regarding the current status of knowledge on manipulation of larval ecology and
chemical-mediated behaviour of adult mosquitoes with plant-derived compounds for
controlling mosquito populations. Further, an update on the current advancements
in technologies to improve longevity and efficiency of these compounds for field
applications has been provided.
PMID- 28412964
TI - MeSH Now: automatic MeSH indexing at PubMed scale via learning to rank.
AB - BACKGROUND: MeSH indexing is the task of assigning relevant MeSH terms based on a
manual reading of scholarly publications by human indexers. The task is highly
important for improving literature retrieval and many other scientific
investigations in biomedical research. Unfortunately, given its manual nature,
the process of MeSH indexing is both time-consuming (new articles are not
immediately indexed until 2 or 3 months later) and costly (approximately ten
dollars per article). In response, automatic indexing by computers has been
previously proposed and attempted but remains challenging. In order to advance
the state of the art in automatic MeSH indexing, a community-wide shared task
called BioASQ was recently organized. METHODS: We propose MeSH Now, an integrated
approach that first uses multiple strategies to generate a combined list of
candidate MeSH terms for a target article. Through a novel learning-to-rank
framework, MeSH Now then ranks the list of candidate terms based on their
relevance to the target article. Finally, MeSH Now selects the highest-ranked
MeSH terms via a post-processing module. RESULTS: We assessed MeSH Now on two
separate benchmarking datasets using traditional precision, recall and F1-score
metrics. In both evaluations, MeSH Now consistently achieved over 0.60 in F
score, ranging from 0.610 to 0.612. Furthermore, additional experiments show that
MeSH Now can be optimized by parallel computing in order to process MEDLINE
documents on a large scale. CONCLUSIONS: We conclude that MeSH Now is a robust
approach with state-of-the-art performance for automatic MeSH indexing and that
MeSH Now is capable of processing PubMed scale documents within a reasonable time
frame. AVAILABILITY: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/MeSHNow/ .
PMID- 28412963
TI - Posttranslationally modified progesterone receptors direct ligand-specific
expression of breast cancer stem cell-associated gene programs.
AB - BACKGROUND: Estrogen and progesterone are potent breast mitogens. In addition to
steroid hormones, multiple signaling pathways input to estrogen receptor (ER) and
progesterone receptor (PR) actions via posttranslational events. Protein kinases
commonly activated in breast cancers phosphorylate steroid hormone receptors
(SRs) and profoundly impact their activities. METHODS: To better understand the
role of modified PRs in breast cancer, we measured total and phospho-Ser294 PRs
in 209 human breast tumors represented on 2754 individual tissue spots within a
tissue microarray and assayed the regulation of this site in human tumor explants
cultured ex vivo. To complement this analysis, we assayed PR target gene
regulation in T47D luminal breast cancer models following treatment with
progestin (promegestone; R5020) and antiprogestins (mifepristone, onapristone, or
aglepristone) in conditions under which the receptor is regulated by Lys388
SUMOylation (K388 intact) or is SUMO-deficient (via K388R mutation to mimic
persistent Ser294 phosphorylation). Selected phospho-PR-driven target genes were
validated by qRT-PCR and following RUNX2 shRNA knockdown in breast cancer cell
lines. Primary and secondary mammosphere assays were performed to implicate
phospho-Ser294 PRs, epidermal growth factor signaling, and RUNX2 in breast cancer
stem cell biology. RESULTS: Phospho-Ser294 PR species were abundant in a majority
(54%) of luminal breast tumors, and PR promoter selectivity was exquisitely
sensitive to posttranslational modifications. Phospho-PR expression and target
gene programs were significantly associated with invasive lobular carcinoma
(ILC). Consistent with our finding that activated phospho-PRs undergo rapid
ligand-dependent turnover, unique phospho-PR gene signatures were most prevalent
in breast tumors clinically designated as PR-low to PR-null (luminal B) and
included gene sets associated with cancer stem cell biology (HER2, PAX2, AHR, AR,
RUNX). Validation studies demonstrated a requirement for RUNX2 in the regulation
of selected phospho-PR target genes (SLC37A2). In vitro mammosphere formation
assays support a role for phospho-Ser294-PRs via growth factor (EGF) signaling as
well as RUNX2 as potent drivers of breast cancer stem cell fate. CONCLUSIONS: We
conclude that PR Ser294 phosphorylation is a common event in breast cancer
progression that is required to maintain breast cancer stem cell fate, in part
via cooperation with growth factor-initiated signaling pathways and key phospho
PR target genes including SLC37A2 and RUNX2. Clinical measurement of
phosphorylated PRs should be considered a useful marker of breast tumor stem cell
potential. Alternatively, unique phospho-PR target gene sets may provide useful
tools with which to identify patients likely to respond to selective PR
modulators that block PR Ser294 phosphorylation as part of rational combination
(i.e., with antiestrogens) endocrine therapies designed to durably block breast
cancer recurrence.
PMID- 28412965
TI - Multireceptor fingerprints in progressive supranuclear palsy.
AB - BACKGROUND: Progressive supranuclear palsy (PSP) with a frontal presentation,
characterized by cognitive deficits and behavioral changes, has been recognized
as an early clinical picture, distinct from the classical so-called Richardson
and parkinsonism presentations. The midcingulate cortex is associated with
executive and attention tasks and has consistently been found to be impaired in
imaging studies of patients with PSP. The aim of the present study was to
determine alterations in neurotransmission underlying the pathophysiology of PSP,
as well as their significance for clinically identifiable PSP subgroups. METHODS:
In vitro receptor autoradiography was used to quantify densities of 20 different
receptors in the caudate nucleus and midcingulate area 24' of patients with PSP
(n = 16) and age- and sex-matched control subjects (n = 14). RESULTS: Densities
of gamma-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor
type 2, and N-methyl-D-aspartate receptors were significantly higher in area 24'
of patients with PSP, where tau impairment was stronger than in the caudate
nucleus. Kainate and nicotinic cholinergic receptor densities were significantly
lower, and adenosine receptor type 1 (A1) receptors significantly higher, in the
caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP
subgroups when clinical parameters such as occurrence of frontal presentation and
tau pathology severity were taken into consideration. CONCLUSIONS: We
demonstrate, for the first time to our knowledge, that kainate and A1 receptors
are altered in PSP and that clinically identifiable PSP subgroups differ at the
neurochemical level. Numerous receptors were altered in the midcingulate cortex,
further suggesting that it may prove to be a key region in PSP. Finally, we add
to the evidence that nondopaminergic systems play a role in the pathophysiology
of PSP, thus highlighting potential novel treatment strategies.
PMID- 28412966
TI - TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced
epithelial to mesenchymal transition.
AB - BACKGROUND: The transition between epithelial and mesenchymal phenotypes (EMT)
occurs in a variety of contexts. It is critical for mammalian development and it
is also involved in tumor initiation and progression. Master transcription factor
(TF) regulators of this process are conserved between mouse and human. METHODS:
From a computational analysis of a variety of high-throughput sequencing data
sets we initially inferred that TFAP2A is connected to the core EMT network in
both species. We then analysed publicly available human breast cancer data for
TFAP2A expression and also studied the expression (by mRNA sequencing), activity
(by monitoring the expression of its predicted targets), and binding (by
electrophoretic mobility shift assay and chromatin immunoprecipitation) of this
factor in a mouse mammary gland EMT model system (NMuMG) cell line. RESULTS: We
found that upon induction of EMT, the activity of TFAP2A, reflected in the
expression level of its predicted targets, is up-regulated in a variety of
systems, both murine and human, while TFAP2A's expression is increased in more
"stem-like" cancers. We provide strong evidence for the direct interaction
between the TFAP2A TF and the ZEB2 promoter and we demonstrate that this
interaction affects ZEB2 expression. Overexpression of TFAP2A from an exogenous
construct perturbs EMT, however, in a manner similar to the downregulation of
endogenous TFAP2A that takes place during EMT. CONCLUSIONS: Our study reveals
that TFAP2A is a conserved component of the core network that regulates EMT,
acting as a repressor of many genes, including ZEB2. REVIEWERS: This article has
been reviewed by Dr. Martijn Huynen and Dr. Nicola Aceto.
PMID- 28412967
TI - Factors associated with lingual tonsil hypertrophy in Canadian adults.
AB - BACKGROUND: Hypertrophy of the lingual tonsil tissue in the adult patient is
thought to contribute to the pathophysiology of obstructive sleep apnea. The
underlying etiology of lingual tonsil hypertrophy (LTH) in the adult patient is
unclear and likely multifactorial. Previous studies have suggested that the
lingual tonsils may undergo compensatory hyperplasia post-tonsillectomy in
children, although it is unknown if this occurs or persists into adulthood. The
purpose of this study was to determine what factors are associated with LTH in a
population of Canadian adults. METHODS: Adult patients presenting for
consultation to an academic Rhinology/General Otolaryngology practice were
eligible for enrollment. Demographic data including age, body mass index (BMI),
Reflux Symptom Index (RSI), history of allergy, and history of tonsillectomy was
collected via questionnaire. Endoscopic photographs of the base of tongue and
larynx were captured. These were graded for LTH and Reflux Finding Scale (RFS) by
blinded examiners. Statistical analysis was performed by comparing the mean LTH
value to the variables of interest using two-tailed T-test. P < .05 was
considered significant. RESULTS: One hundred two subjects were enrolled. Age
ranged from 18 to 78. 28 patients had previous tonsillectomy. This was not
associated with a significant increase in lingual tonsil tissue (r = -0.05, p =
0.61). RFS >7 or RSI >13 was considered positive for laryngopharyngeal reflux.
There was no difference in LTH based on RSI positivity (p = 0.44). RFS positivity
correlated with increased lingual tonsil tissue (p < 0.05). BMI >30 was
associated with increased lingual tonsil hypertrophy (p < 0.05). CONCLUSIONS: An
elevated body mass index and positive Reflux Finding Score are associated with
lingual tonsil hypertrophy in adults. Reflux symptom index, history of allergy
and history of childhood tonsillectomy are not associated with LTH.
PMID- 28412968
TI - Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory
and pro-trophic phenotype in vitro.
AB - BACKGROUND: Inflammation is a key contributor to central nervous system (CNS)
injury such as stroke, and is a major target for therapeutic intervention.
Effective treatments for CNS injuries are limited and applicable to only a
minority of patients. Stem cell-based therapies are increasingly considered for
the treatment of CNS disease, because they can be used as in-situ regulators of
inflammation, and improve tissue repair and recovery. One promising option is the
use of bone marrow-derived mesenchymal stem cells (MSCs), which can secrete anti
inflammatory and trophic factors, can migrate towards inflamed and injured sites
or can be implanted locally. Here we tested the hypothesis that pre-treatment
with inflammatory cytokines can prime MSCs towards an anti-inflammatory and pro
trophic phenotype in vitro. METHODS: Human MSCs from three different donors were
cultured in vitro and treated with inflammatory mediators as follows: interleukin
(IL)-1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha) or interferon
gamma. After 24 h of treatment, cell supernatants were analysed by ELISA for
expression of granulocyte-colony stimulating factor (G-CSF), IL-10, brain-derived
neurotrophic factor (BDNF), nerve growth factor (NGF), IL-1 receptor antagonist
(IL-1Ra) and vascular endothelial growth factor (VEGF). To confirm the anti
inflammatory potential of MSCs, immortalised mouse microglial BV2 cells were
treated with bacterial lipopolysaccharide (LPS) and exposed to conditioned media
(CM) of naive or IL-1-primed MSCs, and levels of secreted microglial-derived
inflammatory mediators including TNF-alpha, IL-10, G-CSF and IL-6 were measured
by ELISA. RESULTS: Unstimulated MSCs constitutively expressed anti-inflammatory
cytokines and trophic factors (IL-10, VEGF, BDNF, G-CSF, NGF and IL-1Ra). MSCs
primed with IL-1alpha or IL-1beta showed increased secretion of G-CSF, which was
blocked by IL-1Ra. Furthermore, LPS-treated BV2 cells secreted less inflammatory
and apoptotic markers, and showed increased secretion of the anti-inflammatory IL
10 in response to treatment with CM of IL-1-primed MSCs compared with CM of
unprimed MSCs. CONCLUSIONS: Our results demonstrate that priming MSCs with IL-1
increases expression of trophic factor G-CSF through an IL-1 receptor type 1 (IL
1R1) mechanism, and induces a reduction in the secretion of inflammatory
mediators in LPS-activated microglial cells. The results therefore support the
potential use of preconditioning treatments of stem cells in future therapies.
PMID- 28412969
TI - Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing
protein regulates the proliferation of glioblastoma stem-like cells.
AB - BACKGROUND: Glioblastoma (GBM), a highly aggressive brain tumor, contains a
subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor
maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising
target for GBM treatment. Our group identified the cellular prion protein (PrPC)
and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential
target candidates due to their role in GBM tumorigenesis and in neural stem cell
maintenance. METHODS: GSCs expressing different levels of PrPC were cultured as
neurospheres with growth factors, and characterized with stem cells markers and
adhesion molecules markers through immunofluorescence and flow cytometry. We than
evaluated GSC self-renewal and proliferation by clonal density assays and BrdU
incorporation, respectively, in front of recombinant HOP treatment, combined or
not with a HOP peptide which mimics the PrPC binding site. Stable silencing of
HOP was also performed in parental and/or PrPC-depleted cell populations, and
proliferation in vitro and tumor growth in vivo were evaluated. Migration assays
were performed on laminin-1 pre-coated glass. RESULTS: We observed that, when GBM
cells are cultured as neurospheres, they express specific stemness markers such
as CD133, CD15, Oct4, and SOX2; PrPC is upregulated compared to monolayer culture
and co-localizes with CD133. PrPC silencing downregulates the expression of
molecules associated with cancer stem cells, upregulates markers of cell
differentiation and affects GSC self-renewal, pointing to a pivotal role for PrPC
in the maintenance of GSCs. Exogenous HOP treatment increases proliferation and
self-renewal of GSCs in a PrPC-dependent manner while HOP knockdown disturbs the
proliferation process. In vivo, PrPC and/or HOP knockdown potently inhibits the
growth of subcutaneously implanted glioblastoma cells. In addition, disruption of
the PrPC-HOP complex by a HOP peptide, which mimics the PrPC binding site,
affects GSC self-renewal and proliferation indicating that the HOP-PrPC complex
is required for GSC stemness. Furthermore, PrPC-depleted GSCs downregulate cell
adhesion-related proteins and impair cell migration indicating a putative role
for PrPC in the cell surface stability of cell adhesion molecules and GBM cell
invasiveness, respectively. CONCLUSIONS: In conclusion, our results show that the
modulation of HOP-PrPC engagement or the decrease of PrPC and HOP expression may
represent a potential therapeutic intervention in GBM, regulating glioblastoma
stem-like cell self-renewal, proliferation, and migration.
PMID- 28412970
TI - Membrane potential independent transport of NH3 in the absence of ammonium
permeases in Saccharomyces cerevisiae.
AB - BACKGROUND: Microbial production of nitrogen containing compounds requires a high
uptake flux and assimilation of the N-source (commonly ammonium), which is
generally coupled with ATP consumption and negatively influences the product
yield. In the industrial workhorse Saccharomyces cerevisiae, ammonium (NH4+)
uptake is facilitated by ammonium permeases (Mep1, Mep2 and Mep3), which
transport the NH4+ ion, resulting in ATP expenditure to maintain the
intracellular charge balance and pH by proton export using the plasma membrane
bound H+-ATPase. RESULTS: To decrease the ATP costs for nitrogen assimilation,
the Mep genes were removed, resulting in a strain unable to uptake the NH4+ ion.
Subsequent analysis revealed that growth of this ?mep strain was dependent on the
extracellular NH3 concentrations. Metabolomic analysis revealed a significantly
higher intracellular NHX concentration (3.3-fold) in the ?mep strain than in the
reference strain. Further proteomic analysis revealed significant up-regulation
of vacuolar proteases and genes involved in various stress responses.
CONCLUSIONS: Our results suggest that the uncharged species, NH3, is able to
diffuse into the cell. The measured intracellular/extracellular NHX ratios under
aerobic nitrogen-limiting conditions were consistent with this hypothesis when
NHx compartmentalization was considered. On the other hand, proteomic analysis
indicated a more pronounced N-starvation stress response in the ?mep strain than
in the reference strain, which suggests that the lower biomass yield of the ?mep
strain was related to higher turnover rates of biomass components.
PMID- 28412971
TI - Appraising the holistic value of Lenvatinib for radio-iodine refractory
differentiated thyroid cancer: A multi-country study applying pragmatic MCDA.
AB - BACKGROUND: The objective of the study was to reveal through pragmatic MCDA
(EVIDEM) the contribution of a broad range of criteria to the value of the orphan
drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC)
in country-specific contexts. METHODS: The study was designed to enable
comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current
disease context (watchful waiting, sorafenib) of France, Italy and Spain. Data on
the value of lenvatinib was collected from diverse stakeholders during country
specific panels and included: criteria weights (individual and social values);
performance scores (judgments on evidence-collected through MCDA systematic
review); qualitative impacts of contextual criteria; and verbal and written
insights structured by criteria. The value contribution of each criterion was
calculated and uncertainty explored. RESULTS: Comparative effectiveness, Quality
of evidence (Spain and Italy) and Disease severity (France) received the greatest
weights. Four criteria contributed most to the value of lenvatinib, reflecting
its superior Comparative effectiveness (16-22% of value), the severity of RR-DTC
(16-22%), significant unmet needs (14-21%) and robust evidence (14-20%).
Contributions varied by comparator, country and individuals, highlighting the
importance of context and consultation. Results were reproducible at the group
level. Impacts of contextual criteria varied across countries reflecting
different health systems and cultural backgrounds. The MCDA process promoted
sharing stakeholders' knowledge on lenvatinib and insights on context.
CONCLUSIONS: The value of lenvatinib was consistently positive across diverse
therapeutic contexts. MCDA identified the aspects contributing most to value,
revealed rich contextual insights, and helped participants express and explicitly
tackle ethical trade-offs inherent to balanced appraisal and decisionmaking.
PMID- 28412972
TI - Mammary microbiota of dairy ruminants: fact or fiction?
AB - Explorations of how the complex microbial communities that inhabit different body
sites might contribute to health and disease have prompted research on the ways
the harmonious relationship between a host and its microbiota could be used to
keep animals healthy in their production conditions. In particular, there is a
growing interest in the bacterial signatures that can be found in the milk of
healthy or mastitic dairy cows. The concept of sterility of the healthy mammary
gland of dairy ruminants has been challenged by the results of studies using
bacterial DNA-based methodology. The newly obtained data have led to the concept
of the intramammary microbiota composed of a complex community of diverse
bacteria. Accordingly, mammary gland infections are not mere infections by a
bacterial pathogen, but the consequence of mammary dysbiosis. This article
develops the logical implications of this paradigm shift and shows how this
concept is incompatible with current knowledge concerning the innate and adaptive
immune system of the mammary gland of dairy ruminants. It also highlights how the
concept of mammary microbiota clashes with results of experimental infections
induced under controlled conditions or large field experiments that demonstrated
the efficacy of the current mastitis control measures.
PMID- 28412973
TI - Genome-wide DNA methylation measurements in prostate tissues uncovers novel
prostate cancer diagnostic biomarkers and transcription factor binding patterns.
AB - BACKGROUND: Current diagnostic tools for prostate cancer lack specificity and
sensitivity for detecting very early lesions. DNA methylation is a stable genomic
modification that is detectable in peripheral patient fluids such as urine and
blood plasma that could serve as a non-invasive diagnostic biomarker for prostate
cancer. METHODS: We measured genome-wide DNA methylation patterns in 73
clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent
prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array.
We overlaid the most significantly differentially methylated sites in the genome
with transcription factor binding sites measured by the Encyclopedia of DNA
Elements consortium. We used logistic regression and receiver operating
characteristic curves to assess the performance of candidate diagnostic models.
RESULTS: We identified methylation patterns that have a high predictive power for
distinguishing malignant prostate tissue from benign-adjacent prostate tissue,
and these methylation signatures were validated using data from The Cancer Genome
Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding
data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene
regulatory regions with higher DNA methylation in malignant prostate tissues.
CONCLUSIONS: DNA methylation patterns are greatly altered in prostate cancer
tissue in comparison to benign-adjacent tissue. We have discovered patterns of
DNA methylation marks that can distinguish prostate cancers with high specificity
and sensitivity in multiple patient tissue cohorts, and we have identified
transcription factors binding in these differentially methylated regions that may
play important roles in prostate cancer development.
PMID- 28412974
TI - Acute hepatitis B virus infection with delayed appearance of hepatitis B core
antibody in an immunocompromised patient: a case report.
AB - BACKGROUND: Despite the introduction of universal hepatitis B immunization
programs worldwide, outbreaks of acute infection still occur in unimmunized
individuals. A timely diagnosis of hepatitis B is necessary to ensure adequate
clinical care and public health interventions that will reduce transmission. Yet,
interpretation of hepatitis B serological markers can be complex. We present a
case of hepatitis B with atypical markers, including delayed appearance of
hepatitis B core antibody. CASE PRESENTATION: A 62-year-old white woman was
identified as a sexual contact of a male individual with acute hepatitis B virus
infection. She had a history of recurrent low-grade non-Hodgkin lymphoma and had
recently received immunosuppressive therapy. At baseline she had a negative
serology and received three double doses (40 MUg) of Engerix-B vaccine (hepatitis
B vaccine) with a 0-month, 1-month, and 6-month schedule. One month following the
last dose, hepatitis B surface antigen was positive in the absence of hepatitis B
core antibody. The only sign of infection was a slight elevation of alanine
aminotransferase enzymes a few months after first sexual contacts with the male
individual. Hepatitis B virus infection was later confirmed despite the absence
of hepatitis B core antibody. The development of hepatitis B core antibody was
finally noted more than 6 months after the first positive hepatitis B surface
antigen and more than 12 months after elevation of alanine aminotransferase
enzymes. Immunosuppression including rituximab treatment was the most likely
explanation for this serological profile. On her last medical assessment, she had
not developed HBeAg seroconversion despite lower hepatitis B virus
deoxyribonucleic acid levels with tenofovir treatment. CONCLUSIONS: When
confronted with positive hepatitis B surface antigen in the absence of hepatitis
B core antibody, consideration should be given to the possibility of both acute
and persistent infection particularly in the setting of immunosuppression so that
appropriate clinical management and public health interventions can take place.
Given the increasing use of biologicals such as anti-tumor necrosis factor
therapies either alone or with other immunosuppressive agents, this phenomenon
may be encountered more frequently.
PMID- 28412975
TI - Effect of cryopreservation on proliferation and differentiation of periodontal
ligament stem cell sheets.
AB - BACKGROUND: Cryopreservation has been extensively applied to the long-term
storage of a diverse range of biological materials. However, no comprehensive
study is currently available on the cryopreservation of periodontal ligament stem
cell (PDLSC) sheets which have been suggested as excellent transplant materials
for periodontal tissue regeneration. The aim of this study is to investigate the
effect of cryopreservation on the structural integrity and functional viability
of PDLSC sheets. METHODS: PDLSC sheets prepared from extracted human molars were
divided into two groups: the cryopreservation group (cPDLSC sheets) and the
freshly prepared control group (fPDLSC sheets). The cPDLSC sheets were
cryopreserved in a solution consisting of 90% fetal bovine serum and 10% dimethyl
sulfoxide for 3 months. Cell viability and cell proliferation rates of PDLSCs in
both groups were evaluated by cell viability assay and 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide (MTT) assay, respectively. The multilineage
differentiation potentials of the cells were assessed by von Kossa staining and
Oil Red O staining. The chromosomal stability was examined by karyotype analysis.
Moreover, the cell sheets in each group were transplanted subcutaneously into the
dorsal site of nude mice, after which Sirius Red staining was performed to
analyze the efficiency of tissue regeneration. RESULTS: The PDLSCs derived from
both groups of cell sheets showed no significant difference in their viability,
proliferative capacities, and multilineage differentiation potentials, as well as
chromosomal stability. Furthermore, transplantation experiments based on a mouse
model demonstrated that the cPDLSC sheets were equally effective in generating
viable osteoid tissues in vivo as their freshly prepared counterparts. In both
cases, the regenerated tissues showed similar network patterns of bone-like
matrix. CONCLUSIONS: Our results offer convincing evidence that cryopreservation
does not alter the biological properties of PDLSC sheets and could enhance their
clinical utility in tissue regeneration.
PMID- 28412976
TI - Hepatic population derived from human pluripotent stem cells is effectively
increased by selective removal of undifferentiated stem cells using YM155.
AB - BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and
induced pluripotent stem cells are promising target cells for cell regenerative
medicine together with recently advanced technology of in-vitro differentiation.
However, residual undifferentiated stem cells (USCs) during in-vitro
differentiation are considered a potential risk for development of cancer cells
and nonspecific lineage cell types. In this study we observed that USCs still
exist during hepatic differentiation, consequently resulting in poor quality of
the hepatic population and forming teratoma in vivo. Therefore, we hypothesized
that effectively removing USCs from in-vitro differentiation could improve the
quality of the hepatic population and guarantee safety from risk of teratoma
formation. METHODS: Human PSCs were differentiated to hepatocytes via four steps.
YM155, a known BIRC5 inhibitor, was applied for removing the residual USCs on the
hepatic differentiation. After YM155 treatment, hepatocyte development was
evaluated by measuring gene expression, immunostaining and hepatic functions at
each stage of differentiation, and forming teratomas were confirmed by cell
transplantation with or without YM155. RESULTS: The selected concentrations of
YM155 removed USCs (NANOG+ and OCT4+) in a dose-dependent manner. As a result,
expression of endodermal markers (SOX17, FOXA2 and CXCR4) at stage II of
differentiation and hepatic markers (ALB, AFP and HNF4A) at stage III was up
regulated by YM155 treatment as well as the hepatic population (ALB+), and
functions (ALB/urea secretion and CYP450 enzyme activity) were enhanced at the
final stage of differentiation (stage IV). Furthermore, we demonstrated that
NANOG and OCT4 expression remaining until stage III (day 15 of differentiation)
completely disappeared when treated with YM155 and teratoma formation was
effectively prevented by YM155 pretreatment in the in-vitro study. CONCLUSIONS:
We suggest that the removal of USCs using YM155 could improve the quantity and
quality of induced hepatocytes and eliminate the potential risk of teratoma
formation.
PMID- 28412977
TI - Noma as a complication of false teeth (Ebiino) extraction: a case report.
AB - BACKGROUND: Ebiino, also known as false tooth extraction, is a traditional
practice done mainly in the remote areas of African countries, including Uganda.
It involves the extraction of tooth buds in babies with common childhood
illnesses such as fever, cough, and diarrhea. It is thought that the tooth buds
are responsible for the ailments seen in these infants. The practice is performed
by traditional healers using unsterile instruments. The complications associated
with this dangerous practice have been mentioned in the literature and include
anemia and septicemia, among others. This case report describes a baby with noma,
an orofacial gangrenous infection. CASE PRESENTATION: A 16-month-old girl from
western Uganda belonging to the Banyankole ethnic group was admitted to Mbarara
University Teaching Hospital with a 5-day history of a dark lesion on the left
cheek. The lesion had started from the left upper gum at the site where a tooth
bud had been extracted 1 week prior to admission. The child had experienced
occasional cough and fever and also had erupting tooth buds. These tooth buds had
been seen as the cause of the cough and fever by the traditional herbalist;
hence, they were extracted. An unsterile instrument had been used for the
procedure. At the hospital, a local examination showed necrotic tissue involving
the left cheek and extending into the left upper gingival area of the girl's
mouth. A clinical diagnosis of orofacial gangrene (noma) was then made.
CONCLUSIONS: Ebiino, or false tooth extraction, is still practiced in some remote
areas of Uganda. Noma has been mentioned as a possible complication of this
traditional practice; however, case reports in the literature are scant. Public
awareness of the dangers of this practice is therefore still required to prevent
this dangerous complication.
PMID- 28412980
TI - Arctic systems in the Quaternary: ecological collision, faunal mosaics and the
consequences of a wobbling climate.
AB - Climate oscillations and episodic processes interact with evolution, ecology and
biogeography to determine the structure and complex mosaic that is the biosphere.
Parasites and parasite-host assemblages are key components in a general
explanatory paradigm for global biodiversity. We explore faunal assembly in the
context of Quaternary time frames of the past 2.6 million years, a period
dominated by episodic shifts in climate. Climate drivers cross a continuum from
geological to contemporary timescales and serve to determine the structure and
distribution of complex biotas. Cycles within cycles are apparent, with drivers
that are layered, multifactorial and complex. These cycles influence the dynamics
and duration of shifts in environmental structure on varying temporal and spatial
scales. An understanding of the dynamics of high-latitude systems, the history of
the Beringian nexus (the intermittent land connection linking Eurasia and North
America) and downstream patterns of diversity depend on teasing apart the
complexity of biotic assembly and persistence. Although climate oscillations have
dominated the Quaternary, contemporary dynamics are driven by tipping points and
shifting balances emerging from anthropogenic forces that are disrupting
ecological structure. Climate change driven by anthropogenic forcing has
supplanted a history of episodic variation and is eliminating ecological barriers
and constraints on development and distribution for pathogen transmission. A
framework to explore interactions of episodic processes on faunal structure and
assembly is the Stockholm Paradigm, which appropriately shifts the focus from
cospeciation to complexity and contingency in explanations of diversity.
PMID- 28412979
TI - Physical exercise for late life depression: effects on cognition and disability.
AB - BACKGROUND: Late-life depression is often associated with cognitive impairments
and disability, which may persist even after adequate antidepressant drug
treatment. Physical exercise is increasingly recognized as an effective
antidepressant agent, and may exert positive effects on these features too.
However, few studies examined this issue, especially by comparing different types
of exercises. METHODS: We performed secondary analyses on data from the Safety
and Efficacy of Exercise for Depression in Seniors study, a trial comparing the
antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non
progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive
aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by
heart rate meters. Patients with late-life depression without severe cognitive
impairment were recruited from primary care and assessed at baseline and 24
weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores)
and Brief Disability Questionnaire. Analyses were based on Generalized Linear
Models. RESULTS: In total, 121 patients (mean age 75, 71% females) were
randomized to the study interventions. Compared with the S group, patients in the
S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect
size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and
disability (p=0.02, effect size=-0.31). Participants in the S+NPE group did not
display significant differences with the control group. CONCLUSIONS: Adding
aerobic, progressive exercise to antidepressant drug treatment may offer
significant advantages over standard treatment for cognitive abilities and
disability. These findings suggest that even among older patients exercise may
constitute a valid therapeutic measure to improve patients' outcomes.
PMID- 28412978
TI - The need for harmonisation and innovation of neuropsychological assessment in
neurodegenerative dementias in Europe: consensus document of the Joint Program
for Neurodegenerative Diseases Working Group.
AB - Cognitive, behavioural, and functional assessment is crucial in longitudinal
studies of neurodegenerative dementias (NDD). Central issues, such as the
definition of the study population (asymptomatic, at risk, or individuals with
dementia), the detection of change/decline, and the assessment of relevant
outcomes depend on quantitative measures of cognitive, behavioural, and
functional status.Currently, we are far from having available reliable protocols
and tools for the assessment of dementias in Europe. The main problems are the
heterogeneity of the tools used across different European countries, the lack of
standardisation of administration and scoring methods across centres, and the
limited information available about the psychometric properties of many tests
currently in widespread use. This situation makes it hard to compare results
across studies carried out in different centres, thus hampering research
progress, in particular towards the contribution to a "big data" common data
set.We present here the results of a project funded by the Joint Program for
Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The
project aimed at providing a consensus framework for the harmonisation of
assessment tools to be applied to research in neurodegenerative disorders
affecting cognition across Europe. A panel of European experts reviewed the
current methods of neuropsychological assessment, identified pending issues, and
made recommendations for the harmonisation of neuropsychological assessment of
neurodegenerative dementias in Europe.A consensus was achieved on the general
recommendations to be followed in developing procedures and tools for
neuropsychological assessment, with the aim of harmonising tools and procedures
to achieve more reliable data on the cognitive-behavioural examination. The
results of this study should be considered as a first step to enhancing a common
view and practise on NDD assessment across European countries.
PMID- 28412981
TI - Differences in the use of everyday technology among persons with MCI, SCI and
older adults without known cognitive impairment.
AB - BACKGROUND: To use valid subjective reports sensible to cognitive decline is
vital to identify very early signs of dementia development. Use of everyday
technology (ET) has been shown to be sensitive to differentiate adults with mild
cognitive impairment (MCI) from controls, but the group with subjective cognitive
impairment (SCI) has not yet been examined. This study aims to investigate and
compare self-perceived ability in ET use and number of ETs reported as actually
used in a sample of older adults with SCI, MCI, and older adults with no known
cognitive impairment, i.e. CONTROLS: METHODS: Older adults with MCI (n = 29),
SCI ( n = 26), and controls (n = 30) were interviewed with the short version of
the Everyday Technology Use Questionnaire (S-ETUQ) to capture self-perceived
ability in ET use and number of ETs used. To generate individual measures of
ability to use ET, Rasch analysis was used. The measures were then compared group
wise using ANCOVA. The numbers of ETs used were compared group-wise with ANOVA.
RESULTS: Controls versus SCI and MCI differed significantly regarding ETs
reported as used, but not SCI versus MCI. Similarly, in ability to use ET,
controls versus SCI and MCI differed significantly but not SCI versus MCI.
CONCLUSIONS: The significantly lower numbers of ETs reported as actually used and
the lower ability in SCI and MCI groups compared to controls suggest that ET use
is affected already in very minor cognitive decline. This indicates that self
reported ET use based on the S-ETUQ is sensitive to detect changes already in
SCI.
PMID- 28412982
TI - Social Isolation in Chinese Older Adults: Scoping Review for Age-Friendly
Community Planning.
AB - Chinese older adults may be at increased risk of social isolation and loneliness,
and a fragmented understanding exists about the challenges they face for social
participation in their neighbourhoods and communities. A scoping review was
undertaken to describe the current knowledge on social isolation and loneliness
in urban-dwelling Chinese older adults living in Western societies to inform
future research, practice, and policy in Canada. Nineteen articles met the
inclusion criteria. The World Health Organization's age-friendly community
framework contextualized the study findings. Studies identified issues related to
(1) social participation; (2) community support and health services; (3) housing;
(4) community and information; (5) respect and social inclusion; (6) outdoor
spaces and public buildings; (7) civic participation and employment; and (8)
transportation. Social isolation and loneliness is a growing concern in this
population in Canada, and additional research is needed to identify its scope and
effective interventions.
PMID- 28412984
TI - Facial carbuncle - a new method of conservative surgical management plus
irrigation with antibiotic-containing solution.
AB - OBJECTIVE: This paper reports on a non-conventional method for the management of
facial carbuncles, highlighting its superiority over conventional surgical
treatment in terms of cosmetic outcome and shorter duration of wound healing.
BACKGROUND: The mainstay of treatment for carbuncles involves the early
administration of antibiotics in combination with surgical intervention. The
conventional saucerisation, or incision and drainage, under normal circumstances
results in moderate to large wounds, which may need secondary surgery such as
skin grafting, resulting in a longer duration of wound healing and jeopardising
cosmetic outcome. CASE REPORTS: The reported three cases presented with extensive
carbuncles over the chin, face and lips region. In addition to early commencement
of intravenous antibiotics, the pus was drained, with minimal incision and
conservative wound debridement, with the aim of maximal skin conservation. This
was followed by thrice-daily irrigation with antibiotic-containing solution for a
minimum of 2 consecutive days. The wounds healed within two to four weeks,
without major cosmetic compromise. CONCLUSION: The new method showed superior
cosmetic outcomes, with a shorter duration of wound healing. Conservative
surgical management can be performed under regional anaesthesia, which may reduce
morbidity and mortality; patients with facial carbuncles often have higher risks
with general anaesthesia.
PMID- 28412983
TI - Piezoelectric technology in otolaryngology, and head and neck surgery: a review.
AB - BACKGROUND: Piezoelectric technology has existed for many years as a surgical
tool for precise removal of soft tissue and bone. The existing literature
regarding its use specifically for otolaryngology, and head and neck surgery was
reviewed. METHODS: The databases Medline, the Cochrane Central Register of
Controlled Trials, PubMed, Embase and Cambridge Scientific Abstracts were
searched. Studies were selected and reviewed based on relevance. RESULTS: Sixty
studies were identified and examined for evidence of benefits and disadvantages
of piezoelectric surgery and its application in otolaryngology. The technique was
compared with traditional surgical methods, in terms of intra-operative bleeding,
histology, learning curve, operative time and post-operative pain. CONCLUSION:
Piezoelectric technology has been successfully employed, particularly in otology
and skull base surgery, where its specific advantages versus traditional drills
include a lack of 'blunting' and tissue selectivity. Technical advantages include
ease of use, a short learning curve and improved visibility. Its higher cost
warrants consideration given that clinically significant improvements in
operative time and morbidity have not yet been proven. Further studies may define
the evolving role of piezoelectric surgery in otolaryngology, and head and neck
surgery.
PMID- 28412985
TI - Active surveillance management of head and neck paragangliomas: case series and
review of the literature.
AB - BACKGROUND: Head and neck paragangliomas are rare. They are usually slow-growing,
benign, non-catecholamine secreting tumours, traditionally treated with surgical
excision. Complications of surgical excision include lower cranial nerve palsies,
stroke and death. METHOD: A retrospective case note analysis was conducted of
patients with head and neck paragangliomas treated with a watch-and-scan policy
from March 2003 to September 2015, and the relevant literature was reviewed.
RESULTS: Fifteen head and neck paragangliomas were identified. None of the
patients developed a new lower cranial nerve palsy or progression of their
presenting hearing loss during the follow-up period. Five patients displayed an
increase in maximum linear dimension of 4 mm over an average of 57.4 months. A
review of the literature showed that a watch-and-surveillance scan policy is
evolving as a treatment option for head and neck paragangliomas without malignant
risk factors. CONCLUSION: Readily available surveillance scanning in head and
neck paragangliomas enables the monitoring of head and neck paragangliomas, which
may allow for avoidance of major surgery.
PMID- 28412987
TI - Back pain in the emergency department: Pathological fracture following spinal
manipulation.
AB - Back pain is one of the most common presentations to the emergency department.
Though case reports of patients presenting with increased back pain following
chiropractic spinal manipulations are rare, we have identified a case rarely
reported in the literature where a potential injury from chiropractic
manipulation resulted in a diagnosis of multiple myeloma. We have reported a
previously healthy 66-year-old male who presented with persistent lower back pain
over 4 weeks. An initial evaluation with thoracolumbar radiographs revealed no
significant findings. Following initial presentation to the family physician, the
patient underwent three treatments of spinal manipulation from his local
chiropractor, which resulted in worsening lower back pain. A re-examination and
new radiographs in the hospital revealed multiple compression fractures and an
underlying diagnosis of multiple myeloma. We have explored current literature
examining the prevalence of lower back pain, as well as the incidence of spinal
fracture following chiropractic manipulation, and have highlighted a potential
complication from chiropractic manipulation in a patient with an undiagnosed
underlying neoplastic disorder.
PMID- 28412986
TI - Effects of subacute ingestion of chlorogenic acids on sleep architecture and
energy metabolism through activity of the autonomic nervous system: a randomised,
placebo-controlled, double-blinded cross-over trial.
AB - Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous
consumption of CGA reduces body fat and body weight. Since energy metabolism and
sleep are controlled by common regulatory factors, consumption of CGA might
modulate sleep. Lack of sleep has been identified as a risk factor for obesity,
hypertension and type 2 diabetes. The aim of this study was to determine the
effects of ingesting CGA over 5 d on energy metabolism and sleep quality in
humans. A total of nine healthy subjects (four male and five female) completed a
placebo-controlled, double-blinded, cross-over intervention study. Subjects
consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth
night, subjects stayed in a whole-room metabolic chamber to measure energy
metabolism; sleep was evaluated using polysomnographic recording. It was found
that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0.05) compared
with the control, whereas no effect on sleep architecture, such as slow-wave
sleep, rapid eye movement or waking after sleep onset, was observed. Indirect
calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem
84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h),
P<0.05) but did not affect energy expenditure during sleep. Consumption of CGA
enhanced parasympathetic activity assessed from heart-rate variability during
sleep (999 (sem 77) v. 919 (sem 54), P<0.05). A period of 5-d CGA consumption
significantly increased fat oxidation during sleep, suggesting that beverages
containing CGA may be beneficial to reduce body fat and prevent obesity.
Consumption of CGA shortened sleep latency and did not adversely affect sleep
quality.
PMID- 28412989
TI - Evaluation of methodological aspects of digestibility measurements in ponies fed
different haylage to concentrate ratios.
AB - Methodological aspects of digestibility measurements were studied in four Welsh
pony geldings consuming haylage-based diets with increasing proportions of a
pelleted concentrate according to a 4*4 Latin square design experiment. Ponies
were fed four experimental, iso-energetic (net energy (NE) basis) diets (i.e. 22
MJ NE/day) with increasing proportions of a pelleted concentrate (C) in relation
to haylage (H). The absolute amounts of diet dry matter fed per day were 4.48 kg
of H (100H), 3.36 and 0.73 kg of H and C (75H25C), 2.24 and 1.45 kg of H and C
(50H50C) and 1.12 and 2.17 kg of H and C (25H75C). Diets were supplemented with
minerals, vitamins and TiO2 (3.7 g Ti/day). Voluntary voided faeces were
quantitatively collected daily during 10 consecutive days and analysed for
moisture, ash, ADL, acid-insoluble ash (AIA) and Ti. A minimum faeces collection
period of 6 consecutive days, along with a 14-day period to adapt the animals to
the diets and become accustomed to the collection procedure, is recommended to
obtain accurate estimations on dry matter digestibility and organic matter
digestibility (OMD) in equids fed haylage-based diets supplemented with
concentrate. In addition, the recovery of AIA, ADL and Ti was determined and
evaluated. Mean faecal recovery over 10 consecutive days across diets for AIA,
ADL and Ti was 124.9% (SEM 2.9), 108.7% (SEM 2.0) and 97.5% (SEM 0.9),
respectively. Cumulative faecal recovery of AIA significantly differed between
treatments, indicating that AIA is inadequate to estimate the OMD in equines. In
addition, evaluation of the CV of mean cumulative faecal recoveries obtained by
AIA, ADL and Ti showed greater variations in faecal excretion of AIA (9.1) and
ADL (7.4) than Ti (3.7). The accuracy of prediction of OMD was higher with the
use of Ti than ADL. The use of Ti is preferred as a marker in digestibility
trials in equines fed haylage-based diets supplemented with increasing amounts of
pelleted concentrate.
PMID- 28412990
TI - Influence of pre-storage incubation on hatchability traits, thyroid hormones,
antioxidative status and immunity of newly hatched chicks at two chicken breeder
flock ages.
AB - Egg storage longer than 7 days is associated with negative effects on
hatchability traits. Pre-storage incubation has been a suggested method to reduce
the negative effects of long-term storage times by enhancing the developmental
stage of the embryo and probably reducing the embryonic stress. The objective of
the present study was to investigate the effects of pre-storage incubation and
storage time on hatchability characteristics, chick quality and serum thyroid
hormones, antioxidative properties and immunoglobulin Y (IgY) concentrations of
newly hatched chicks at two breeder flock ages. A total of 8000 fertile eggs were
obtained from two different ages of chicken breeder hens (Egyptian local cross,
Inshas). Half of the eggs were collected from young breeder hens (28 weeks old)
and the other half from old breeder hens (50 weeks old). In each breeder flock
age, eggs were distributed in a completely randomized experimental design in a
2*4 factorial arrangement, with two storage periods (4 or 14 days) and four pre
storage incubation durations (0, 4, 6 or 8 h at 37.5 degrees C). At 28 and 50
weeks of age, pre-storage incubation and its interaction with storage period
influenced significantly the apparent fertility, hatchability of set eggs and
hatchability of fertile eggs and this improvement in hatchability is attributed
to the reduction in embryonic mortality (early, intermediate and late). Pre
storage incubation for 6 or 8 h elevated significantly the grade A chicks and
reduced the grade B chicks in comparison with non-heated controls. Interestingly,
for eggs stored for 14 days, pre-storage incubation for 6 or 8 h enhanced serum
triiodothyronine, thyroxine, glutathione peroxidase activity, total antioxidant
capacity and IgY concentrations significantly and decreased serum malondialdehyde
concentration significantly in the newly hatched chicks. It could be concluded
that pre-storage incubation enhanced the hatching results, improved the
antioxidative properties, reduced lipid peroxidation and elevated the humoral
immunity in the newly hatched chicks. Hence, several benefits might be gained by
pre-storage incubation when fertilized eggs will be stored for long periods.
PMID- 28412991
TI - Inbreeding effects on in vitro embryo production traits in Guzera cattle.
AB - Inbreeding has been associated with the impairment of reproductive performance in
many cattle breeds. Although the usage of reproductive biotechnologies has been
increasing in bovine populations, not much attention has been given to the impact
of inbreeding over cow's performance on artificial reproduction. The objective of
this study was to estimate the impact of inbreeding on in vitro embryo production
in a Guzera breed population. The inbreeding coefficient (F), calculated as half
of the co-ancestry of the individual's parents, was used as an estimate of
inbreeding. The inbreeding coefficients of the donor, sire (used on in vitro
fertilization) and of the embryos were included, separately, in the proposed
models either as classificatory or continuous variables (linear and quadratic
effects). The percentage of non-inbred individuals (or embryos) and mean F of
donors, embryos and sires were 29.38%; 35.76%; 42.86% and 1.98+/-2.68; 1.32+/
3.13; 2.08+/-2.79, respectively. Two different models were considered, one for
oocyte production traits and other for embryo production traits. The increase of
F of the donor significantly (P<0.05) impaired the number of viable oocytes (N
OV), number of grade I oocytes (N GI) and number of cleaved embryos (N CLV).
Moreover, the donor's F influenced the percentage of grade I oocytes (P GI),
percentage of viable embryos (P EMB) and percentage of cleaved embryos that
turned into embryos (P CXE). No significant (P>0.05) effects were observed for
the sire (father of the embryos) inbreeding coefficient over the traits analysed.
Embryo's F influenced (P<0.05) the number of viable embryos (N EMB), percentage
of viable embryos (P EMB) and percentage of cleaved embryos that turn into
embryos (P CXE). Results suggested that an increase in the inbreeding coefficient
might impair the embryos ability to survive through challenges imposed by the in
vitro environment. Submitting highly inbred Guzera female donors to in vitro
embryo production may, in the long-term, have negative implications on the number
of embryos obtained per cow and increase the relative costs of the improvement
programmes based on this technology. High levels of inbreeding should be avoided
when selecting Guzera female donors and planning in vitro fertilization mating.
PMID- 28412992
TI - Acute otitis media associated bilateral sudden hearing loss: case report and
literature review.
AB - BACKGROUND: Sudden sensorineural hearing loss is a rare otological condition with
potential for dire outcomes including permanent hearing loss. Although the
majority of cases are deemed idiopathic, bilateral sudden sensorineural hearing
loss represents a rare subset typically related to systemic conditions, with
higher morbidity and mortality. A controversial association with acute otitis
media has been reported, with few bilateral cases published in the literature.
CASE REPORT: A very rare case of bilateral sudden sensorineural hearing loss
associated with acute otitis media is described, with a review of the literature.
CONCLUSION: The limited evidence available suggests that acute otitis media with
tinnitus and/or bacterial pathology may have an increased risk of sudden
sensorineural hearing loss, which is consistent with the case described. Although
there is no sufficiently powered published evidence to provide definitive
treatment guidelines, the literature reviewed suggests that early myringotomy and
antibiotics may greatly improve treatment outcomes.
PMID- 28412993
TI - Paediatric-onset coronary artery anomalies in pregnancy: a single-centre
experience and systematic literature review.
AB - OBJECTIVES: Individuals with childhood-onset coronary artery anomalies are at
increased risk of lifelong complications. Although pregnancy is thought to confer
additional risk, a few data are available regarding outcomes in this group of
women. We sought to define outcomes of pregnancy in this unique population.
METHODS: We performed a retrospective survey of women with paediatric-onset
coronary anomalies and pregnancy in our institution, combined with a systematic
review of published cases. We defined paediatric-onset coronary artery anomalies
as congenital coronary anomalies and inflammatory arteriopathies of childhood
that cause coronary aneurysms. Major cardiovascular events were defined as
pulmonary oedema, sustained arrhythmia requiring treatment, stroke, myocardial
infarction, cardiac arrest, or death. RESULTS: A total of 25 surveys were mailed,
and 20 were returned (80% response rate). We included 46 articles from the
literature, which described cardiovascular outcomes in 82 women (138
pregnancies). These data were amalgamated for a total of 102 women and 194
pregnancies; 59% of women were known to have paediatric-onset coronary artery
anomalies before pregnancy. In 23%, the anomaly was unmasked during or shortly
after pregnancy. The remainder, 18%, was diagnosed later in life. Major
cardiovascular events occurred in 14 women (14%) and included heart failure (n=5,
5%), myocardial infarction (n=7, 7%), maternal death (n=2, 2%), cardiac arrest
secondary to ventricular fibrillation (n=1, 1%), and stroke (n=1, 1%). The
majority of maternal events (13/14, 93%) occurred in women with no previous
diagnosis of coronary disease. CONCLUSIONS: Women with paediatric-onset coronary
artery anomalies have a 14% risk of adverse cardiovascular events in pregnancy,
indicating the need for careful assessment and close follow-up. Prospective,
multicentre studies are required to better define risk and predictors of
complications during pregnancy.
PMID- 28412994
TI - Effects of high-fat diet on somatic growth, metabolic parameters and function of
peritoneal macrophages of young rats submitted to a maternal low-protein diet.
AB - This study evaluated the effects of a post-weaning high-fat (HF) diet on somatic
growth, food consumption, metabolic parameters, phagocytic rate and nitric oxide
(NO) production of peritoneal macrophages in young rats submitted to a maternal
low-protein (LP) diet. Male Wistar rats (aged 60 d) were divided in two groups (n
22/each) according to their maternal diet during gestation and lactation: control
(C, dams fed 17 % casein) and LP (dams fed 8 % casein). At weaning, half of the
groups were fed HF diet and two more groups were formed (HF and low protein-high
fat (LP-HF)). Somatic growth, food and energy intake, fat depots, serum glucose,
cholesterol and leptin concentrations were evaluated. Phagocytic rate and NO
production were analysed in peritoneal macrophages under stimulation of zymosan
and lipopolysaccharide (LPS)+interferon gamma (IFN-gamma), respectively. The
maternal LP diet altered the somatic parameters of growth and development of
pups. LP and LP-HF pups showed a higher body weight gain and food intake than C
pups. HF and LP-HF pups showed increased retroperitoneal and epididymal fat
depots, serum level of TAG and total cholesterol compared with C and LP pups.
After LPS+IFN-gamma stimulation, LP and LP-HF pups showed reduced NO production
when compared with their pairs. Increased phagocytic activity and NO production
were seen in LP but not LP-HF peritoneal macrophages. However, peritoneal
macrophages of LP pups were hyporesponsive to LPS+IFN-gamma induced NO release,
even after a post-weaning HF diet. Our data demonstrated that there was an
immunomodulation related to dietary fatty acids after the maternal LP diet
induced metabolic programming.
PMID- 28412995
TI - Development and validation of Prediction models for Risks of complications in
Early-onset Pre-eclampsia (PREP): a prospective cohort study.
AB - BACKGROUND: The prognosis of early-onset pre-eclampsia (before 34 weeks'
gestation) is variable. Accurate prediction of complications is required to plan
appropriate management in high-risk women. OBJECTIVE: To develop and validate
prediction models for outcomes in early-onset pre-eclampsia. DESIGN: Prospective
cohort for model development, with validation in two external data sets. SETTING:
Model development: 53 obstetric units in the UK. Model transportability: PIERS
(Pre-eclampsia Integrated Estimate of RiSk for mothers) and PETRA (Pre-Eclampsia
TRial Amsterdam) studies. PARTICIPANTS: Pregnant women with early-onset pre
eclampsia. SAMPLE SIZE: Nine hundred and forty-six women in the model development
data set and 850 women (634 in PIERS, 216 in PETRA) in the transportability
(external validation) data sets. PREDICTORS: The predictors were identified from
systematic reviews of tests to predict complications in pre-eclampsia and were
prioritised by Delphi survey. MAIN OUTCOME MEASURES: The primary outcome was the
composite of adverse maternal outcomes established using Delphi surveys. The
secondary outcome was the composite of fetal and neonatal complications.
ANALYSIS: We developed two prediction models: a logistic regression model (PREP
L) to assess the overall risk of any maternal outcome until postnatal discharge
and a survival analysis model (PREP-S) to obtain individual risk estimates at
daily intervals from diagnosis until 34 weeks. Shrinkage was used to adjust for
overoptimism of predictor effects. For internal validation (of the full models in
the development data) and external validation (of the reduced models in the
transportability data), we computed the ability of the models to discriminate
between those with and without poor outcomes (c-statistic), and the agreement
between predicted and observed risk (calibration slope). RESULTS: The PREP-L
model included maternal age, gestational age at diagnosis, medical history,
systolic blood pressure, urine protein-to-creatinine ratio, platelet count, serum
urea concentration, oxygen saturation, baseline treatment with antihypertensive
drugs and administration of magnesium sulphate. The PREP-S model additionally
included exaggerated tendon reflexes and serum alanine aminotransaminase and
creatinine concentration. Both models showed good discrimination for maternal
complications, with anoptimism-adjusted c-statistic of 0.82 [95% confidence
interval (CI) 0.80 to 0.84] for PREP-L and 0.75 (95% CI 0.73 to 0.78) for the
PREP-S model in the internal validation. External validation of the reduced PREP
L model showed good performance with a c-statistic of 0.81 (95% CI 0.77 to 0.85)
in PIERS and 0.75 (95% CI 0.64 to 0.86) in PETRA cohorts for maternal
complications, and calibrated well with slopes of 0.93 (95% CI 0.72 to 1.10) and
0.90 (95% CI 0.48 to 1.32), respectively. In the PIERS data set, the reduced PREP
S model had a c-statistic of 0.71 (95% CI 0.67 to 0.75) and a calibration slope
of 0.67 (95% CI 0.56 to 0.79). Low gestational age at diagnosis, high urine
protein-to-creatinine ratio, increased serum urea concentration, treatment with
antihypertensive drugs, magnesium sulphate, abnormal uterine artery Doppler scan
findings and estimated fetal weight below the 10th centile were associated with
fetal complications. CONCLUSIONS: The PREP-L model provided individualised risk
estimates in early-onset pre-eclampsia to plan management of high- or low-risk
individuals. The PREP-S model has the potential to be used as a triage tool for
risk assessment. The impacts of the model use on outcomes need further
evaluation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40384046.
FUNDING: The National Institute for Health Research Health Technology Assessment
programme.
PMID- 28412996
TI - Laparoscopic surgery versus open resection in patients with gastrointestinal
stromal tumors: An updated systematic review and meta-analysis.
AB - PURPOSES: The contemporary surgery has reported the safety of laparoscopic
surgery (LAP) for patients with gastrointestinal stromal tumors (GISTs). However,
its use is still debated due to suspicion of the oncologic equivalence to open
surgery (OPEN). We conducted a systematic review and meta-analysis of updated
original articles to investigate the short- and long-term clinical outcomes of
LAP compared with OPEN for GISTs. METHODS: A systematic search was performed in
PubMed, Embase, Web of Science, Cochrane Library and CNKI. Comparative studies of
laparoscopic and open surgery for GISTs were published before November 2016. The
Newcastle-Ottawa scale was utilized to conduct quality assessment. The Review
Manager (RevMan) software version 5.0 was used for meta-analysis. RESULTS: Twenty
four studies involving 2140 patients were included for the meta-analysis. The
meta-analysis results showed that, compared with OPEN, LAP indicated potentially
favorable outcomes in terms of operative time (WMD, -30.71; 95% CI, -58.48 to
2.95; P = 0.03); intraoperative blood loss (WMD, -60.90; 95% CI, -91.53 to
30.28; P < 0.0001); time to flatus (WMD, -1.10; 95% CI, -1.41 to -0.79; P <
0.00001); time to oral intake (WMD, -1.25; 95% CI, -1.64 to -0.86; P < 0.00001);
length of hospital stay (WMD, -3.42; 95% CI, -4.37 to -2.46; P < 0.00001);
overall complications (OR, 0.38; 95% CI, 0.27 to 0.54; P < 0.00001); and
recurrence (OR, 0.45; 95% CI, 0.30 to 0.66; P < 0.0001). CONCLUSIONS:
Laparoscopic surgery is safe and feasible for the treatment of GISTs including
less operative time and intraoperative blood loss, earlier postoperative
recovery, shorter hospital stay, and lower rate of overall complications and
recurrence.
PMID- 28412997
TI - Erythematous Lesion on the Nose.
PMID- 28412998
TI - New hPSC-based human models to study pediatric Acute Megakaryoblastic Leukemia
harboring the fusion oncogene RBM15-MKL1.
AB - Pediatric Acute Megakaryoblastic Leukemia not associated to Down Syndrome (non-DS
AMKL) is a rare disease with a dismal prognosis. Around 15% of patients carry the
chromosomal translocation t(1;22) that originates the fusion oncogene RBM15-MKL1,
which is linked to an earlier disease onset (median of 6months of age) and arises
in utero. Here we report the generation of two hPSC cell lines constitutively
expressing the oncogene RBM15-MKL1, resulting in an increased expression of known
RBM15-MKL1 gene targets. These cell lines represent new disease models of
pediatric AMKL to study the impact of the RBM15-MKL1 oncogene on human embryonic
hematopoietic development.
PMID- 28412999
TI - Generation of an induced pluripotent stem cell line from chorionic villi of a
Turner syndrome spontaneous abortion.
AB - A major cause of spontaneous abortions is chromosomal abnormality of foetal
cells. We report the generation of an induced pluripotent stem cell line from the
fibroblasts isolated from chorionic villi of an early spontaneously aborted
foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem
cell line is transgene free, retains the original XO karyotype, expresses
pluripotency markers and undergoes trilineage differentiation. This pluripotent
stem cell model of Turner syndrome should serve as a tool to study the
developmental abnormalities of foetus and placenta that lead to early embryo
lethality and profound symptoms like infertility in 45 XO survivors.
PMID- 28413000
TI - Derivation of mouse embryonic stem cell lines from tyrosine hydroxylase reporter
mice crossed with a human SNCA transgenic mouse model of Parkinson's disease.
AB - Mouse embryonic stem cell (mESC) lines were derived by crossing heterozygous
transgenic (tg) mice expressing green fluorescent protein (GFP) under the control
of the rat tyrosine hydroxylase (TH) promoter, with homozygous alpha-synuclein
(aSYN) mice expressing human mutant SNCAA53T under the control of the mouse Prion
promoter (MoPrP), or wildtype (WT) mice. The expression of GFP and human aSYN was
validated by immunocytochemistry in midbrain neuron cultures upon differentiation
of mESC lines using stromal cell-derived inducing activity. These mESC lines can
help to study the impact of human aSYN expression in neurons and
oligodendrocytes, and also trace GFP-expressing midbrain neurons.
PMID- 28413001
TI - Development of human induced pluripotent stem cell (iPSC) line from a 60year old
female patient with multiple schwannoma.
AB - Peripheral blood was collected from a clinically diagnosed 60-year old female
patient with multiple schwannoma. Peripheral blood mononuclear cells (PBMCs) were
reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus
reprogramming system. The transgene-free iPSC line showed pluripotency verified
by immunofluorescent staining for pluripotency markers, and the iPSC line was
able to differentiate into the 3 germ layers in vivo. The iPSC line also showed
normal karyotype. This in vitro cellular model will be useful for further
pathological studies of multiple schwannoma.
PMID- 28413002
TI - Characterization of human induced pluripotent stem cell (iPSC) line from a 72year
old male patient with later onset Alzheimer's disease.
AB - Peripheral blood was collected from a clinically diagnosed 72-year old male
patient with later onset Alzheimer's disease. Peripheral blood mononuclear cells
(PBMCs) were reprogrammed with the Yamanaka KMOS reprogramming factors using the
Sendai-virus reprogramming system. The transgene-free iPSC line showed
pluripotency verified by immunofluorescent staining for pluripotency markers, and
the iPSC line was able to differentiate into the 3 germ layers in vivo. The iPSC
line also showed normal karyotype. This in vitro cellular model will be useful
for studying the pathological mechanism of Alzheimer's disease.
PMID- 28413003
TI - Induced pluripotent stem cells derived from a patient with autosomal dominant
familial neurohypophyseal diabetes insipidus caused by a variant in the AVP gene.
AB - Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is
caused by variants in the arginine vasopressin (AVP) gene. Here we report the
generation of induced pluripotent stem cells (iPSCs) from a 42-year-old man
carrying an adFNDI causing variant in exon 1 of the AVP gene using lentivirus
mediated nuclear reprogramming. The iPSCs carried the expected variant in the AVP
gene. Furthermore, the iPSCs expressed pluripotency markers; displayed in vitro
differentiation potential to the three germ layers and had a normal karyotype
consistent with the original fibroblasts. This iPSC line is useful in future
studies focusing on the pathogenesis of adFNDI.
PMID- 28413004
TI - Derivation of human induced pluripotent stem cell (iPSC) line from a 79year old
sporadic male Parkinson's disease patient.
AB - Peripheral blood was collected from a clinically diagnosed 79-year old male
sporadic Parkinson's disease patient. Peripheral blood mononuclear cells (PBMCs)
were reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai
virus reprogramming system. The transgene-free iPSC line showed pluripotency
verified by immunofluorescent staining for pluripotency markers, and the iPSC
line was able to differentiate into the 3 germ layers in vivo. The iPSC line also
showed normal karyotype. This in vitro cellular model can be used to study the
mechanism of sporadic Parkinson's disease and to test new drugs. Resource Table.
PMID- 28413005
TI - Generation of a Nrf2 homozygous knockout human embryonic stem cell line using
CRISPR/Cas9.
AB - Nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2) is a well-known
transcription factor that regulates the expression of a large number of anti
oxidant genes in mammalian cells (J.H. Kim et al., 2014). Here, we generated a
homozygous Nrf2 knockout human embryonic stem cell (hESC) line, H9Nrf2KO-A13,
using the CRISPR/Cas9 genome editing method. The Nrf2 homozygous knockout H9 cell
line maintains pluripotency, differentiation potential into three germ layers,
and a normal karyotype.
PMID- 28413006
TI - Generation of a human induced pluripotent stem cell (iPSC) line from a 64year old
male patient with multiple schwannoma.
AB - Peripheral blood was collected from a clinically diagnosed 64-year old male
multiple schwannoma patient. Peripheral blood mononuclear cells (PBMCs) were
reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus
reprogramming system. The transgene-free iPSC line showed pluripotency verified
by immunofluorescent staining for pluripotency markers, and the iPSC line was
able to differentiate into the 3 germ layers in vivo. The iPSC line also showed
normal karyotype. This in vitro cellular model will be useful for further
pathological studies of multiple schwannoma.
PMID- 28413007
TI - A homozygous Keap1-knockout human embryonic stem cell line generated using
CRISPR/Cas9 mediates gene targeting.
AB - Kelch-like ECH-associated protein 1 (keap1) is a cysteine-rich protein that
interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to
the degradation of Nrf2 (Kim et al., 2014a). Disruption of Keap1 results in the
induction of Nrf2-related signaling pathways involving the expression of a set of
anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the
Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic
stem cell (hESC). The Keap1 homozygous-knockout H9 cell line retained normal
morphology, gene expression, and in vivo differentiation potential.
PMID- 28413008
TI - ?
PMID- 28413009
TI - ?
PMID- 28413010
TI - [An example of a network supporting elderly people].
AB - One of a health network's main missions is to favour access to care and to
decompartmentalise the management of patients' treatment. With regard to the
coordination of the pathways of elderly people, the 'Access to Care, Access to
Rights, Health Education' network operating in the Hauts-de-Seine region aims to
support health professionals in establishing and coordinating the health pathway
of people in complex situations. It is a question of trust, cooperation, multi
professionality and exchanges.
PMID- 28413011
TI - [Nurse coordinator and doctor coordinator in a gerontology network].
AB - The Marseille gerontology network consists of a geriatric team providing support
in patients' homes across the Marseille urban area. It forms an integral part of
the geriatric care sector ensuring that elderly people living at home benefit
from a global medical-psychological-social assessment. The aim is to enable
elderly people to continue living and receiving care in their home.
PMID- 28413012
TI - [Identifying frailty and the importance of personalised support].
AB - Over recent years, many hospitals have been looking to promote optimum ageing by
developing a strategy for identifying frailty in elderly people. This raises the
question of prevention in the field of ageing and the capacities to change
behaviour which is harmful to health at any age. Early and long-term support is
essential.
PMID- 28413013
TI - [Adaptation of the home, the occupational therapist's assessment].
AB - When the functional independence of elderly people starts to diminish, the choice
of adapted assistive devices and some simple modifications to the home can allow
them to continue to perform their daily tasks safely and easily. Likewise, when
physical dependency is established, the choice of relevant assistive devices
enables these people to continue living in their home in the right conditions,
both for the person concerned as well as for their direct carers. In these
different situations, the assessment by the occupational therapist enables the
solutions to be adjusted to the capacities, the morphology and the lifestyles of
the elderly person.
PMID- 28413014
TI - [The PASA, a unique place of interconnection].
AB - The PASA, a centre for adapted activities and care, enables nursing homes to
become places of progress and innovation in the management of residents suffering
from Alzheimer's disease and related conditions. The multidisciplinary approach
and the convergence of new perspectives enables some to revive essential threads
of their identity, and others to evolve and build themselves through more
rewarding experiences.
PMID- 28413015
TI - [What to do before a hypervitaminia B12 in the elderly].
AB - Hypervitanimia B12 is an early marker of serious pathologies. These include solid
neoplasms, malignant blood diseases and acute/chronic hepatopathies.
Hypervitaminemia B12 in geriatrics is thereby an indicator in the diagnosis and
prognosis of these conditions.
PMID- 28413016
TI - ?
PMID- 28413017
TI - ?
PMID- 28413020
TI - gammadelta T Cells and B Cells.
AB - gammadelta T cells constitute the third arm of a tripartite adaptive immune
system in jawed vertebrates, besides alphabeta T cells and B cells. Like the
other two lymphocyte-types, they express diverse antigen receptors, capable of
specific ligand recognition. Functionally, gammadelta T cells represent a system
of differentiated subsets, sometimes engaged in cross-regulation, which
ultimately determines their effect on other components of the immune system,
including B cells and antibodies. gammadelta T cells are capable of providing
help to B cells in antibody production. More recently it became clear that
gammadelta T cells influence B cell differentiation during the peripheral stages
of B cell development, control levels of circulating immunoglobulin (all
subclasses), and affect production of autoantibodies. Because of this
relationship between gammadelta T cells and B cells, the extensive variation of
gammadelta T cells among human individuals might be expected to modulate their
humoral responsiveness.
PMID- 28413019
TI - Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with
Both Familial and Sporadic Pituitary Adenomas.
AB - Pituitary adenoma (PA) is one of the most common intracranial neoplasms. Several
genetic predisposing factors for PA have been identified, but they account for a
small portion of cases. In this study, we sought to identify the PA genetic risk
factors by focusing on causative mutations for PAs. Among the 4 affected and 17
asymptomatic members from one family with familial PA, whole-exome sequencing
identified cosegregation of the PA phenotype with the heterozygous missense
mutation c.4136G>T (p.Arg1379Leu) in cadherin-related 23 (CDH23). This mutation
causes an amino acid substitution in the calcium-binding motif of the
extracellular cadherin (EC) domains of CDH23 and is predicted to impair cell-cell
adhesion. Genomic screening in a total of 12 families with familial PA (20
individuals), 125 individuals with sporadic PA, and 260 control individuals
showed that 33% of the families with familial PA (4/12) and 12% of individuals
with sporadic PA (15/125) harbored functional CDH23 variants. In contrast, 0.8%
of the healthy control individuals (2/260) carried functional CDH23 variants.
Gene-based analysis also revealed a significant association between CDH23
genotype and PA (p = 5.54 * 10-7). Moreover, PA individuals who did not harbor
functional CDH23 variants displayed tumors that were larger in size (p = 0.005)
and more invasive (p < 0.001). Therefore, mutations in CDH23 are linked with
familial and sporadic PA and could play important roles in the pathogenesis of
PA.
PMID- 28413018
TI - PLAA Mutations Cause a Lethal Infantile Epileptic Encephalopathy by Disrupting
Ubiquitin-Mediated Endolysosomal Degradation of Synaptic Proteins.
AB - During neurotransmission, synaptic vesicles undergo multiple rounds of exo
endocytosis, involving recycling and/or degradation of synaptic proteins. While
ubiquitin signaling at synapses is essential for neural function, it has been
assumed that synaptic proteostasis requires the ubiquitin-proteasome system
(UPS). We demonstrate here that turnover of synaptic membrane proteins via the
endolysosomal pathway is essential for synaptic function. In both human and
mouse, hypomorphic mutations in the ubiquitin adaptor protein PLAA cause an
infantile-lethal neurodysfunction syndrome with seizures. Resulting from
perturbed endolysosomal degradation, Plaa mutant neurons accumulate K63
polyubiquitylated proteins and synaptic membrane proteins, disrupting synaptic
vesicle recycling and neurotransmission. Through characterization of this
neurological intracellular trafficking disorder, we establish the importance of
ubiquitin-mediated endolysosomal trafficking at the synapse.
PMID- 28413021
TI - Regulation of Innate and Adaptive Immunity by TGFbeta.
AB - Immune regulation by cytokines is crucial in maintaining immune homeostasis,
promoting responses to infection, resolving inflammation, and promoting
immunological memory. Additionally, cytokine responses drive pathology in immune
mediated disease. A crucial cytokine in the regulation of all aspects of an
immune response is transforming growth factor beta (TGFbeta). Although best known
as a crucial regulator of T cell responses, TGFbeta plays a vital role in
regulating responses mediated by virtually every innate and adaptive immune cell,
including dendritic cells, B cells, NK cells, innate lymphoid cells, and
granulocytes. Here, we review our current knowledge of how TGFbeta regulates the
immune system, highlighting the multifunctional nature of TGFbeta and how its
function can change depending on location and context of action.
PMID- 28413024
TI - Tissue-Specific Diversity and Functions of Conventional Dendritic Cells.
AB - Dendritic cells (DCs) are versatile controllers of immunity, which sense
infection or tissue damage and, accordingly, initiate innate and adaptive
effector responses. In recent years, it has become evident that DCs exist as an
independent hematopoietic lineage comprising several developmentally distinct and
functionally specialized subsets that are strategically located in all organs to
defend the organism against invading pathogens. Here, we review the diversity of
DC subtypes found across tissues and discuss our current understanding of the
tissue-specific functions of these cell types.
PMID- 28413023
TI - A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic Stem
Cells to Mature B Lymphocytes.
AB - B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone
marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs)
and sinusoidal endothelial cells. These niches are defined by function and
location: MSPCs are mostly perisinusoidal cells that together with a small subset
of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7),
IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are
morphologically heterogeneous, highly reticular, and form a vast cellular network
in the bone marrow parenchyma capable of interacting with large numbers of
hematopoietic cells. HSCs, downstream multipotent progenitor cells, and common
lymphoid progenitor cells utilize CXCR4 to fine-tune access to critical short
range growth factors provided by MSPCs for their long-term maintenance and/or
multilineage differentiation. In later stages, developing B lymphocytes use CXCR4
to navigate the bone marrow parenchyma, and predominantly cannabinoid receptor-2
for positioning within bone marrow sinusoids, prior to being released into
peripheral blood circulation. In the final stages of differentiation,
transitional B cells migrate to the spleen where they preferentially undergo
further rounds of differentiation until selection into the mature B cell pool
occurs. This bottleneck purges up to 97% of all developing B cells in a
peripheral selection process that is heavily controlled not only by the intensity
of BCR signaling and access to BAFF but also by the proper functioning of the B
cell motility machinery.
PMID- 28413026
TI - The Balance Between Metalloproteinases and TIMPs: Critical Regulator of
Microvascular Endothelial Cell Function in Health and Disease.
AB - Endothelial cells (EC), especially the microvascular EC (MVEC), have critical
functions in health and disease. For example, healthy MVEC provide a barrier
between the fluid and protein found within the blood, and the surrounding tissue.
Following tissue injury or infection, the microvascular barrier is often
disrupted due to activation and dysfunction of the MVEC. Multiple mechanisms
promote MVEC activation and dysfunction, including stimulation by cytokines,
mechanical interaction with activated leukocytes, and exposure to harmful
leukocyte-derived molecules, which collectively result in a loss of MVEC barrier
function. However, MVEC activation is also critical to facilitate recruitment of
inflammatory cells, such as neutrophils (PMNs) and monocytes, into the injured or
infected tissue. Metalloproteinases, including the matrix metalloproteinases
(MMPs) and the closely related, a disintegrin and metalloproteinases (ADAMs),
have been implicated in regulating both MVEC barrier function, through cleavage
of adherens and tight junctions proteins between adjacent MVEC and through
degradation of the extracellular matrix, as well as PMN-MVEC interaction, through
shedding of cell surface PMN receptors. Moreover, the tissue inhibitors of
metalloproteinases (TIMPs), which collectively inhibit most MMPs and ADAMs, are
critical regulators of MVEC activation and dysfunction through their ability to
inhibit metalloproteinases and thereby promote MVEC stability. However, TIMPs
have been also found to modulate MVEC function through metalloproteinase
independent mechanisms, such as regulation of vascular endothelial growth factor
signaling. This chapter is focused on examining the role of the
metalloproteinases and TIMPs in regulation of MVEC function in both health and
disease.
PMID- 28413022
TI - Humanized Immunoglobulin Mice: Models for HIV Vaccine Testing and Studying the
Broadly Neutralizing Antibody Problem.
AB - A vaccine that can effectively prevent HIV-1 transmission remains paramount to
ending the HIV pandemic, but to do so, will likely need to induce broadly
neutralizing antibody (bnAb) responses. A major technical hurdle toward achieving
this goal has been a shortage of animal models with the ability to systematically
pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on
their ability to stimulate bnAb development. Over the past 6 years,
immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs
in mice, an approach that has enabled elucidation of various B-cell tolerance
mechanisms limiting bnAb production and evaluation of strategies to circumvent
such processes. From these studies, in conjunction with the wealth of information
recently obtained regarding the evolutionary pathways and paratopes/epitopes of
multiple bnAbs, it has become clear that the very features of bnAbs desired for
their function will be problematic to elicit by traditional vaccine paradigms,
necessitating more iterative testing of new vaccine concepts. To meet this need,
novel bnAb KI models have now been engineered to express either inferred
prerearranged V(D)J exons (or unrearranged germline V, D, or J segments that can
be assembled into functional rearranged V(D)J exons) encoding predecessors of
mature bnAbs. One encouraging approach that has materialized from studies using
such newer models is sequential administration of immunogens designed to bind
progressively more mature bnAb predecessors. In this review, insights into the
regulation and induction of bnAbs based on the use of KI models will be
discussed, as will new Ig KI approaches for higher-throughput production and/or
altering expression of bnAbs in vivo, so as to further enable vaccine-guided bnAb
induction studies.
PMID- 28413027
TI - Matrix Metalloproteinases and Platelet Function.
AB - Platelets contain and release several matrix metalloproteinases (MMPs) and their
tissue inhibitors of matrix metalloproteinases (TIMPs), including MMP-1, -2, -3,
9, and -14 and TIMP-1, -2, and -4. Although devoid of a nucleus, platelets also
synthesize TIMP-2 upon activation. Platelet-released MMPs/TIMPs, as well as MMPs
generated by other cells within the cardiovascular system, modulate platelet
function in health and disease. In particular, a normal hemostatic platelet
response to vessel wall injury may be transformed into pathologic thrombus
formation by the release from platelets and/or by the local generation of some
MMPs. Moreover, platelets may localize the production of leukocyte-derived MMPs
to sites of vascular damage, contributing to atherosclerosis development and
complications and to arterial aneurysm formation. Finally, the interaction
between platelets and tumor cells is strongly influenced by MMPs/TIMPs. All these
mechanisms are emerging as important in atherothrombosis, inflammatory disease,
and cancer growth and dissemination. Increasing knowledge of these mechanisms may
open the way to novel therapeutic approaches.
PMID- 28413028
TI - Matrix Metalloproteinases and Leukocyte Activation.
AB - As their name implies, matrix metalloproteinases (MMPs) are thought to degrade
extracellular matrix proteins, a function that is indeed performed by some
members. However, regardless of their cell source, matrix degradation is not the
only function of these enzymes. Rather, individual MMPs have been shown to
regulate specific immune processes, such as leukocyte influx and migration,
antimicrobial activity, macrophage activation, and restoration of barrier
function, typically by processing a range of nonmatrix protein substrates.
Indeed, MMP expression is low under steady-state conditions but is markedly
induced during inflammatory processes including infection, wound healing, and
cancer. Increasing research is showing that MMPs are not just a downstream
consequence of a generalized inflammatory process, but rather are critical
factors in the overall regulation of the pattern, type, and duration of immune
responses. This chapter outlines the role of leukocytes in tissue remodeling and
describes recent progress in our understanding of how MMPs alter leukocyte
activity.
PMID- 28413025
TI - Biochemical and Biological Attributes of Matrix Metalloproteinases.
AB - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases
that are involved in the degradation of various proteins in the extracellular
matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic
metalloproteinase domain with catalytic zinc, a hinge region or linker peptide,
and a hemopexin domain. MMPs are commonly classified on the basis of their
substrates and the organization of their structural domains into collagenases,
gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs.
MMPs are secreted by many cells including fibroblasts, vascular smooth muscle
(VSM), and leukocytes. MMPs are regulated at the level of mRNA expression and by
activation of their latent zymogen form. MMPs are often secreted as inactive pro
MMP form which is cleaved to the active form by various proteinases including
other MMPs. MMPs cause degradation of ECM proteins such as collagen and elastin,
but could influence endothelial cell function as well as VSM cell migration,
proliferation, Ca2+ signaling, and contraction. MMPs play a role in tissue
remodeling during various physiological processes such as angiogenesis,
embryogenesis, morphogenesis, and wound repair, as well as in pathological
conditions such as myocardial infarction, fibrotic disorders, osteoarthritis, and
cancer. Increases in specific MMPs could play a role in arterial remodeling,
aneurysm formation, venous dilation, and lower extremity venous disorders. MMPs
also play a major role in leukocyte infiltration and tissue inflammation. MMPs
have been detected in cancer, and elevated MMP levels have been associated with
tumor progression and invasiveness. MMPs can be regulated by endogenous tissue
inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines
the extent of ECM protein degradation and tissue remodeling. MMPs have been
proposed as biomarkers for numerous pathological conditions and are being
examined as potential therapeutic targets in various cardiovascular and
musculoskeletal disorders as well as cancer.
PMID- 28413029
TI - Evidence for the Involvement of Matrix-Degrading Metalloproteinases (MMPs) in
Atherosclerosis.
AB - Atherosclerosis leads to blockage of arteries, culminating in myocardial
infarction, and stroke. The involvement of matrix-degrading metalloproteinases
(MMPs) in atherosclerosis is established and many studies have highlighted the
importance of various MMPs in this process. MMPs were first implicated in
atherosclerosis due to their ability to degrade extracellular matrix components,
which can lead to increased plaque instability. However, more recent work has
highlighted a multitude of roles for MMPs in addition to breakdown of
extracellular matrix proteins. MMPs are now known to be involved in various
stages of plaque progression: from initial macrophage infiltration to plaque
rupture. This chapter summarizes the development and progression of
atherosclerotic plaques and the contribution of MMPs. We provide data from human
studies showing the effect of MMP polymorphisms and the expression of MMPs in
both the atherosclerotic plaque and within plasma. We also discuss work in animal
models of atherosclerosis that show the effect of gain or loss of function of
MMPs. Together, the data provided from these studies illustrate that MMPs are
ideal targets as both biomarkers and potential drug therapies for
atherosclerosis.
PMID- 28413030
TI - The Role Matrix Metalloproteinases in the Production of Aortic Aneurysm.
AB - Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of
aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and
abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle
cells in the aortic media and the destruction of extracellular matrix (ECM).
Furthermore, AAA have evidence of inflammation and the cellular elements involved
in inflammation such as macrophages can produce and/or activate MMPs This chapter
focuses on human aortic aneurysm that are not due to specific known genetic
causes because this type of aneurysm is the more common type. This chapter will
also focus on MMP protein expression rather than on genetic data which may not
necessarily translate to increased MMP protein expression. There are supporting
data that certain MMPs are increased in the aortic wall. For TAA, it is most
notably MMP-1, -9, -12, and -14 and MMP-2 when a bicuspid aortic valve is
present. For AAA, it is MMP-1, -2, -3, -9, -12, and -13. The data are weaker or
insufficient for the other MMPs. Several studies of gene polymorphisms support
MMP-9 for TAA and MMP-3 for AAA as potentially important factors. The signaling
pathways in the aorta that can lead to MMP activation include JNK, JAK/stat,
osteopontin, and AMP-activated protein kinase alpha2. Substrates in the human
vasculature for MMP-3, MMP-9, or MMP-14 include collagen, elastin, ECM
glycoprotein, and proteoglycans. Confirmed and potential substrates for MMPs,
maintain aortic size and function so that a reduction in their content relative
to other components of the aortic wall may produce a failure to maintain aortic
size leading to dilatation and aneurysm formation.
PMID- 28413033
TI - Preface.
PMID- 28413034
TI - Preface: Optimizing science impact for effective implementation of Sustainable
Land Management.
PMID- 28413035
TI - Vasa Previa: A Cautious Approach at Caesarean Section.
PMID- 28413031
TI - Matrix Metalloproteinases in Remodeling of Lower Extremity Veins and Chronic
Venous Disease.
AB - The veins of the lower extremity are equipped with efficient wall, contractile
vascular smooth muscle (VSM), and competent valves in order to withstand the high
venous hydrostatic pressure in the lower limb and allow unidirectional movement
of deoxygenated blood toward the heart. The vein wall structure and function are
in part regulated by matrix metalloproteinases (MMPs). MMPs are zinc-dependent
endopeptidases that are secreted as inactive pro-MMPs by different cells in the
venous wall including fibroblasts, VSM, and leukocytes. Pro-MMPs are activated by
other MMPs, proteinases, and other endogenous and exogenous activators. MMPs
degrade various extracellular matrix (ECM) proteins including collagen and
elastin, and could affect other cellular processes including endothelium-mediated
dilation, VSM cell migration, and proliferation as well as modulation of Ca2+
signaling and contraction in VSM. It is thought that increased lower limb venous
hydrostatic pressure increases hypoxia-inducible factors and other MMP inducers
such as extracellular matrix metalloproteinase inducer, leading to increased MMP
expression/activity, ECM protein degradation, vein wall relaxation, and venous
dilation. Vein wall inflammation and leukocyte infiltration cause additional
increases in MMPs, and further vein wall dilation and valve degradation, that
could lead to chronic venous disease and varicose veins (VVs). VVs are often
presented as vein wall dilation and tortuosity, incompetent venous valves, and
venous reflux. Different regions of VVs show different MMP levels and ECM
proteins with atrophic regions showing high MMP levels/activity and little ECM
compared to hypertrophic regions with little or inactive MMPs and abundant ECM.
Treatment of VVs includes compression stockings, venotonics, sclerotherapy, or
surgical removal. However, these approaches do not treat the cause of VVs, and
other lines of treatment may be needed. Modulation of endogenous tissue
inhibitors of metalloproteinases (TIMPs), and exogenous synthetic MMP inhibitors
may provide new approaches in the management of VVs.
PMID- 28413036
TI - ?
PMID- 28413032
TI - Matrix Metalloproteinases in Myocardial Infarction and Heart Failure.
AB - Cardiovascular disease is the leading cause of death, accounting for 600,000
deaths each year in the United States. In addition, heart failure accounts for
37% of health care spending. Matrix metalloproteinases (MMPs) increase after
myocardial infarction (MI) and correlate with left ventricular dysfunction in
heart failure patients. MMPs regulate the remodeling process by facilitating
extracellular matrix turnover and inflammatory signaling. Due to the critical
role MMPs play during cardiac remodeling, there is a need to better understand
the pathophysiological mechanism of MMPs, including the biological function of
the downstream products of MMP proteolysis. Future studies developing new
therapeutic targets that inhibit specific MMP actions to limit the development of
heart failure post-MI are warranted. This chapter focuses on the role of MMPs
post-MI, the efficiency of MMPs as biomarkers for MI or heart failure, and the
future of MMPs and their cleavage products as targets for prevention of post-MI
heart failure.
PMID- 28413037
TI - A Return to Training Days Gone By: A Case for a Uniform Report Card System for
Gynaecologic Surgery.
PMID- 28413038
TI - ?
PMID- 28413039
TI - Excerpts from the World Medical Literature.
PMID- 28413040
TI - ?
PMID- 28413041
TI - Defining Cervical Elongation: A Prospective Observational Study.
AB - OBJECTIVES: Our primary aim was to define cervical elongation (CE) using the
following methods: (1) measurement of pathology specimen, (2) physician
perception, (3) intraoperative estimate of anterior cervical length, and (4)
office Pelvic Organ Prolapse Quantification (POP-Q) points C and D. Our secondary
aim was to determine whether these definitions correlate with perioperative
outcomes. METHODS: Women undergoing vaginal hysterectomy and prolapse repair were
enrolled. Office POP-Q measurements were collected. Estimates of cervical length
were made based on points C minus D of the POP-Q and by manual exam using the
surgeon's index and middle fingers. Cervical dimensions were measured from the
pathology specimen at the end of the case. CE was defined as one standard
deviation (SD) above the mean for each definition. Additional intraoperative data
was collected to determine the surgeon perception of cervical anatomy. RESULTS: A
total of 90 patients were enrolled during the study period. Our definitions for
CE were as follows: (1) 5 cm (70 without and 20 with CE), (2) physician
perception (67 without and 23 with CE), (3) 3.4 cm (79 without and 11 with CE),
and (4) 8.3 cm (77 without and 13 with CE). After controlling for uterine weight
and the presence of fibroids, the operative time was the only outcome measure
that remained elevated for patients with CE using our first definition (42.4 +/-
20.1 without vs. 53.8 +/- 19.2 with CE, P = 0.03). CONCLUSIONS: CE using our
first definition was associated with a statistically significant increase in
operative time in women undergoing hysterectomy at the time of prolapse repair.
PMID- 28413042
TI - No. 329-Canadian Contraception Consensus Part 4 of 4 Chapter 9: Combined Hormonal
Contraception.
AB - OBJECTIVE: To provide guidelines for health care providers on the use of
contraceptive methods to prevent pregnancy and on the promotion of healthy
sexuality. OUTCOMES: Overall efficacy of cited contraceptive methods, assessing
reduction in pregnancy rate, safety, and side effects; the effect of cited
contraceptive methods on sexual health and general well-being; and the
availability of cited contraceptive methods in Canada. EVIDENCE: Medline and the
Cochrane Database were searched for articles in English on subjects related to
contraception, sexuality, and sexual health from January 1994 to December 2015 in
order to update the Canadian Contraception Consensus published February-April
2004. Relevant Canadian government publications and position papers from
appropriate health and family planning organizations were also reviewed. VALUES:
The quality of the evidence is rated using the criteria described in the Report
of the Canadian Task Force on Preventive Health Care. Recommendations for
practice are ranked according to the method described in this report. SUMMARY
STATEMENTS: RECOMMENDATIONS.
PMID- 28413043
TI - ?
AB - OBJECTIF: Mettre a la disposition des fournisseurs de soins des lignes
directrices concernant le recours a des methodes contraceptives pour prevenir la
grossesse et la promotion d'une sexualite saine. ISSUES: Efficacite globale des
methodes contraceptives citees : evaluation de l'innocuite, des effets
indesirables et de la baisse du taux de grossesse; effet des methodes
contraceptives citees sur la sante sexuelle et le bien-etre general;
disponibilite des methodes contraceptives citees au Canada. ReSULTATS: Des
recherches ont ete effectuees dans MEDLINE et la base de donnees Cochrane afin
d'en tirer les articles en anglais publies entre janvier 1994 et decembre 2015
traitant de sujets lies a la contraception, a la sexualite et a la sante
sexuelle, dans le but de mettre a jour le consensus canadien sur la contraception
paru de fevrier a avril 2004. Nous avons egalement passe en revue les
publications pertinentes du gouvernement canadien, ainsi que les declarations de
principes issues d'organisations competentes vouees a la sante et a la
planification familiale. VALEURS: La qualite des resultats a ete evaluee au moyen
des criteres decrits par le Groupe d'etude canadien sur les soins de sante
preventifs. Les recommandations quant a la pratique sont classees en fonction de
la methode decrite dans le rapport du Groupe. DeCLARATIONS SOMMAIRES:
RECOMMANDATIONS.
PMID- 28413044
TI - Expression profiling feline peripheral blood monocytes identifies a
transcriptional signature associated with type two diabetes mellitus.
AB - Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes
(T2D) in humans, especially with respect to the role of obesity-induced insulin
resistance, glucose toxicity, decreased number of pancreatic beta-cells and
pancreatic amyloid deposition. Cats have thus been proposed as a valuable
translational model of T2D. In humans, inflammation associated with adipose
tissue is believed to be central to T2D development, and peripheral blood
monocytes (PBM) are important in the inflammatory cascade which leads to insulin
resistance and beta-cell failure. PBM may thus provide a useful window to study
the pathogenesis of diabetes mellitus in cats, however feline monocytes are
poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to
profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with
normal glucose tolerance. Feline monocytes were enriched for genes expressed in
human monocytes, and, despite heterogeneous gene expression, we identified a T2D
associated expression signature associated with cell cycle perturbations, DNA
repair and the unfolded protein response, oxidative phosphorylation and
inflammatory responses. Our data provide novel insights into the feline monocyte
transcriptome, and support the hypothesis that inflammatory monocytes contribute
to T2D pathogenesis in cats as well as in humans.
PMID- 28413045
TI - Effector mechanisms of humoral immunity to porcine reproductive and respiratory
syndrome virus.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) continues to afflict
swine nearly 30 years after it was first discovered as the causative agent of
"mystery swine disease". Immunological tools of vaccination and exposure to
virulent viruses have not succeeded in achieving control and prevention of PRRSV.
Humoral immunity, mediated by antibodies, is a hallmark of anti-viral immunity,
but little is known about the effector mechanisms of humoral immunity against
PRRSV. It is essential to understand the immunological significance of antibody
functions, including recently described broadly neutralizing antibodies and
potential non-neutralizing activities, in the immune response to PRRSV. Here, we
review recent research from PRRSV and other host-pathogen interactions to inform
novel routes of exploration into PRRSV humoral immunity which may be important
for identifying the immunological correlates of protection against PRRSV
infection.
PMID- 28413046
TI - Heat stress decreases expression of the cytokines, avian beta-defensins 4 and 6
and Toll-like receptor 2 in broiler chickens infected with Salmonella
Enteritidis.
AB - A high ambient temperature is a highly relevant stressor in poultry production.
Heat stress (HS) has been reported to reduce animal welfare, performance indices
and increase Salmonella susceptibility. Salmonella spp. are major zoonotic
pathogen that cause over 1 billion of human infections worldwide annually.
Therefore, the current study was designed to analyze the effect of heat stress on
Salmonella infection in chickens through modulation of the immune responses.
Salmonella Enteritidis was inoculated via gavage at one day of age (106cfu/mL).
Heat stress 31+/-1 degrees C was applied from 35 to 41 days of age. Broiler
chickens were divided into the following groups of 12 chickens: control (C); heat
stress (HS31 degrees C); S. Enteritidis positive control (PC); and S.
Enteritidis+heat stress (PHS31 degrees C). We observed that heat stress increased
corticosterone serum levels. Concomitantly heat stress decreased (1) the IgA and
IFN-gamma plasmatic levels; (2) the mRNA expression of IL-6, IL-12 in spleen and
IL-1beta, IL-10, TGF-beta in cecal tonsils; (3) the mRNA expression of AvBD4 and
AvBD6 in cecal tonsils; and (4) the mRNA expression of TLR2 in spleen and cecal
tonsils of chickens infected with S. Enteritidis (PHS31 degrees C group). Heat
stress also increased Salmonella colonization in the crop and caecum as well as
Salmonella invasion to the spleen, liver and bone marrow, showing a deficiency in
the control of S. Enteritidis induced infection. Together, the present data
suggested that heat stress activated hypothalamus-pituitary-adrenal (HPA) axis,
as observed by the increase in the corticosterone levels, which in turn
presumably decreases the immune system activity, leading to an impairment of the
intestinal mucosal barrier and increasing chicken susceptibility to the invasion
of different organs by S. Enteritidis .
PMID- 28413047
TI - A homolog of teleostean signal transducer and activator of transcription 3
(STAT3) from rock bream, Oplegnathus fasciatus: Structural insights,
transcriptional modulation, and subcellular localization.
AB - Signal transducer and activator of transcription 3 (STAT3) is one of the crucial
transcription factors in the Janus kinase (JAK)/STAT signaling pathway, and it
was previously considered as acute phase response factor. A number of
interleukins (ILs) such as IL-5, IL-6, IL-9, IL-10, IL-12, and IL-22 are known to
be involved in activation of STAT3. In addition, various growth factors and
pathogenic or oxidative stresses mediate the activation of a wide range of
functions via STAT3. In this study, a STAT3 homolog was identified and
functionally characterized from rock bream (RbSTAT3), Oplegnathus fasciatus. In
silico characterization revealed that the RbSTAT3 amino acid sequence shares
highly conserved common domain architectural features including N-terminal
domain, coiled coil domain, DNA binding domain, linker domain, and Src homology 2
(SH2) domains. In addition, a fairly conserved transcriptional activation domain
(TAD) was located at the C-terminus. Comparison of RbSTAT3 with other
counterparts revealed higher identities (>90%) with fish orthologs. The genomic
sequence of RbSTAT3 was obtained from a bacterial artificial chromosome (BAC)
library, and was identified as a multi-exonic gene (24 exons), as found in other
vertebrates. Genomic structural comparison and phylogenetic studies have showed
that the evolutionary routes of teleostean and non-teleostean vertebrates were
distinct. Quantitative real time PCR (qPCR) analysis revealed that the spatial
distribution of RbSTAT3 mRNA expression was ubiquitous and highly detectable in
blood, heart, and liver tissues. Transcriptional modulation of RbSTAT3 was
examined in blood and liver tissues after challenges with bacteria (Edwardsiella
tarda and Streptococcus iniae), rock bream irido virus (RBIV), and immune
stimulants (LPS and poly (I:C)). Significant changes in RbSTAT3 transcription
were also observed in response to tissue injury. In addition, the transcriptional
up-regulation of RbSTAT3 was detected in rock bream heart cells upon recombinant
rock bream IL-10 (rRbIL-10) treatment. Subcellular localization and nuclear
translocation of rock bream STAT3 following poly (I:C) treatment were also
demonstrated. Taken together, the results of the current study provide important
evidence for potential roles of rock bream STAT3 in the immune system and wound
healing processes.
PMID- 28413048
TI - Milk C-reactive protein in canine mastitis.
AB - Presence of mastitis in lactating bitches can become life threatening for both
the bitch and pups. The aim of the present study was to evaluate a possible
utility of C-reactive protein (CRP) in both milk and serum for canine mastitis
diagnosis. Our study showed that milk CRP levels ranged between 0.1 and 4.9MUg/mL
and from 0.3 to 40.0MUg/mL in healthy and diseased bitches (P<0.01),
respectively, while serum CRP levels ranged between 2.0 and 8.6MUg/mL and between
0.3 and 162.3MUg/mL in healthy and diseased bitches (P<0.01), respectively. Milk
and serum CRP levels were higher in both clinical and subclinical mastitis when
compared with healthy controls (P<0.05 in all cases). However, no significant
differences were recorded in CRP concentrations between clinical and subclinical
cases. Based on these results, it could be concluded that serum and milk CRP
could be useful in order to diagnose canine mastitis.
PMID- 28413049
TI - Evaluation of blood T-lymphocyte subpopulations involved in host cellular
immunity in dogs with mammary cancer.
AB - Cancer-bearing patients are often immunosuppressed. In dogs with mammary or other
cancers, various alterations in blood cell populations involved in host cellular
immunity have been reported; among these cell populations some T-lymphocyte
subsets play an important role against cancer. The purpose of the present study
was to investigate any alterations in circulating T-lymphocyte subpopulations
involved in cellular immunity in bitches with mammary cancer, in comparison to
age-matched healthy intact bitches. Twenty eight dogs with mammary cancer and 14
control dogs were included in this study. Twelve out of the 28 bitches had
mammary cancer of clinical stage II and 16/28 of stage III. Histological
examination revealed that 23/28 animals had carcinomas, 3/28 sarcomas and 2/28
carcinosarcomas. White blood cell, neutrophil and lymphocyte absolute numbers
were measured by complete blood count. Furthermore, blood T-lymphocyte population
(CD3+) and the subpopulations CD4+, CD8+ and CD5low+ were assessed by flow
cytometry. White blood cell and neutrophil but not lymphocyte absolute numbers
were higher (P=0.003 and P=0.001, respectively) in cancer patients than controls.
Flow cytometric analysis revealed that the relative percentage of T-lymphocytes
(CD3+) and of CD4+, CD8+ subpopulations was lower (the CD4+/CD8+ ratio was
higher), whereas the percentage of CD5low+ T-cells was higher, in dogs with
cancer compared to controls; however, a statistically significant difference was
found only in the case of CD8+ T-cells (P=0.014), whereas in the case of the
CD4+/CD8+ ratio the difference almost reached statistical significance (P=0.059).
Based on these findings, it can be suggested that, although the absolute number
of blood lymphocytes is unchanged, the relative percentages of T-lymphocyte
subpopulations involved in host cell-mediated immunity are altered, but only
cytotoxic CD8+ T-cells are significantly suppressed, in dogs with mammary cancer
of clinical stage II or III compared to age-matched healthy controls.
PMID- 28413050
TI - Toll-like receptor 2 gene polymorphisms in Chinese Holstein cattle and their
associations with bovine tuberculosis.
AB - This study evaluated whether there was an association between polymorphisms
within the Toll-like receptor 2 gene (TLR2) of Chinese Holstein cattle and
susceptibility to bovine tuberculosis (BTB). In a case-control study including
210 BTB cases and 237 control cattle, we found only two common single-nucleotide
polymorphisms (SNPs) within the entire coding region of the TLR2 gene, A631G
(rs95214857) and T1707C (rs1388116488). Additionally, the allele and genotype
distributions of A631G and T1707C were not different between case and control
groups, indicated that these SNPs were not associated with susceptibility to BTB.
These results suggested that polymorphisms in the TLR2 gene might not play a
significant role in the BTB risk in Chinese Holstein cattle.
PMID- 28413051
TI - Protective efficacy of a novel recombinant Marek's disease virus vector vaccine
against infectious bursal disease in chickens with or without maternal
antibodies.
AB - Infectious bursal disease (IBD) causes significant clinical and economic losses
to the poultry industry worldwide. Current vaccine programs using live attenuated
and inactivated vaccines have numerous drawbacks. As an alternative solution to
control IBD, a Marek's disease virus (MDV) vector vaccine (rMDV-VP2) expressing
the VP2 gene of infectious bursal disease virus (IBDV) has been developed. In
this study, the protective efficacy of rMDV-VP2 was evaluated in a dose-related
experiment which showed that a single dose of 1000 PFU was sufficient to fully
protect chickens against IBDV infection. Chickens inoculated with lower doses of
rMDV-VP2 (250 or 500 PFU) conferred 80 and 90% protection against IBDV. Next,
rMDV-VP2 vaccine provided 90% protection against IBDV in commercial layer
chickens with maternal antibodies, which was higher than the protective efficacy
using the B87 live vaccine of IBDV. Additionally, rMDV-VP2 conferred effective
protection against very virulent MDV challenge in chickens (95% for chickens
vaccinated with 250 or 500 PFU and 100% for chickens vaccinated with 1000 or 2000
PFU). These results demonstrated that rMDV-VP2 may be a novel bivalent vaccine
against IBD and Marek's disease in chickens.
PMID- 28413052
TI - Purified natural pig immunoglobulins can substitute dietary zinc in reducing
piglet post weaning diarrhoea.
AB - Enteric infectious disease in weaner piglets, including postweaning diarrhoea
(PWD), are usually treated and/or prevented with antibiotics and/or zinc oxide in
the piglet feed. However extensive use of antibiotics and zinc oxide in intensive
animal production is unwanted as it may promote microbial antibiotic resistance
and pose environmental problems. Recently, in an experimental model of PWD, we
observed that oral administration of purified porcine immunoglobulin G (ppIgG)
from pooled natural pig plasma could reduce enteric infection. In the present
study we were able to reproduce these results as it was observed that oral ppIgG
accelerated clearance of faecal haemolytic bacteria in pigs challenged with E.
coli in comparison with pigs not receiving ppIgG. This effect was observed upon
feeding ppIgG for seven days postweaning suggesting that ppIgG does not have to
be used prophylactically for several days preweaning. Furthermore, the effect of
oral administration of ppIgG for seven days postweaning was equal to or better
than that of dietary zinc oxide in reducing diarrhoea symptoms and in clearing
faecal haemolytic bacteria for 14days postweaning. These observations warrant
future trials of dietary ppIgG in intensive swine production units to establish
its performance as an alternative to dietary antibiotics and zinc oxide for
preventing PWD.
PMID- 28413053
TI - Introduction.
PMID- 28413054
TI - Corrigendum to "Evidence of substantial development of inhibitory control and
sustained attention between 6 and 8years of age on an unpredictable Go/No-Go
task" [J. Exp. Child Psychol. 157 (2017) 66-80].
PMID- 28413055
TI - Functional Genomics and High Content Screening in the Nervous System.
PMID- 28413056
TI - Impact of scalp location on survival in head and neck melanoma: A retrospective
cohort study.
AB - BACKGROUND: Scalp melanomas have more aggressive clinicopathological features
than other melanomas and mortality rates more than twice that of melanoma located
elsewhere. OBJECTIVE: We sought to describe the survival of patients with scalp
melanoma versus other cutaneous head and neck melanoma (CHNM), and explore a
possible independent negative impact of scalp location on CHNM survival. METHODS:
A retrospective cohort study was performed of all invasive primary CHNM cases
seen at a tertiary referral center over a 20-year period. Melanoma-specific
survival (MSS) was compared between scalp melanoma and other invasive CHNM.
Multivariable Cox proportional hazards regression was performed to determine
associations with survival. RESULTS: On univariate analysis, patients with scalp
melanoma had worse MSS than other CHNM (hazard ratio 2.22, 95% confidence
interval 1.59-3.11). Scalp location was not associated with MSS in CHNM on
multivariable analysis (hazard ratio 1.11, 95% confidence interval 0.77-1.61) for
all tumors together, but remained independently associated with MSS for the 0.76-
to 1.50-mm thickness stratum (hazard ratio 5.51, 95% confidence interval 1.55
19.59). LIMITATIONS: Disease recurrence was not assessed because of unavailable
data. CONCLUSION: The poorer survival of scalp melanoma is largely explained by
greater Breslow thickness and a higher proportion of male patients.
PMID- 28413058
TI - Erythromelalgia: Identification of a corticosteroid-responsive subset.
AB - BACKGROUND: Corticosteroids (CS) may benefit certain patients with
erythromelalgia. OBJECTIVES: Our objective was to determine clinical predictors
of corticosteroid-responsive erythromelalgia. METHODS: Patients with
erythromelalgia who received CS were identified and stratified into
corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs),
complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs +
CSRs). In the study variable analysis, P < .05 was considered statistically
significant. RESULTS: The median (interquartile range) age of the 31-patient
cohort was 47 years (26-57 years), and 22 (71%) were female. Fourteen (45%) were
NRs, 17 (55%) SRs, 8 (26%) PSRs, and 9 (29%) CSRs. A subacute temporal profile to
disease zenith (<21 days) was described in 15 (48%) patients, of whom 13 (87%)
were SRs (P = .003; odds ratio [OR] = 0.069 [95% confidence interval {CI}, 0.011
0.431]). Six (67%) CSRs reported a disease precipitant (eg, surgery, trauma, or
infection; P = .007; OR = 12.667 [95% CI, 2-80.142]). SR patients received CS
sooner than NR at 3 (3-12) versus 24 (17-45) months (P = .003). A high-dose CS
trial (>=200 mg prednisone cumulatively) was administered to 17 (55%) patients,
of whom 13 (76%) were SRs (P = .012; OR = 8.125 [95% CI, 1.612-40.752]).
LIMITATIONS: This was a retrospective case series. CONCLUSION: An infectious,
traumatic, or surgical precipitant and subacute presentation may portend CR
erythromelalgia. A transient "golden window" where CS intervention is useful may
exist before irreversible nociceptive remodeling and central sensitization
occurs.
PMID- 28413057
TI - Sex differences in the association of cutaneous melanoma incidence rates and
geographic ultraviolet light exposure.
AB - BACKGROUND: Cutaneous melanoma (CM) incidence rates continue to increase, and the
reasons are unknown. Previously, we reported a unique age-specific sex difference
in melanoma that suggested additional causes other than solar ultraviolet (UV)
radiation. OBJECTIVE: This study attempted to understand whether and how UV
radiation differentially impacts the CM incidence in men and women. METHODS: CM
data and daily UV index (UVI) from 31 cancer registries were collected for
association analysis. A second dataset from 42 US states was used for validation.
RESULTS: There was no association between log-transformed female CM rates and
levels of UVI, but there was a significant association between male rates and UVI
and a significant association between overall rates and UVI. The 5-year age
specific rate-UVI association levels (represented by Pearson's coefficient rho)
increased with age in men, but age-specific rho levels remained low and unchanged
in women. The significant rate-UVI association in men and nonassociation in women
was validated in a population of white residents of the United States.
LIMITATIONS: Confounders, including temperature and latitude, are difficult to
separate from UVI. CONCLUSIONS: Ambient UVI appears to be associated with
melanoma incidence in males but not in females.
PMID- 28413059
TI - Viral exanthems: An update on laboratory testing of the adult patient.
AB - Although classic viral exanthems of childhood are well described, they are rarely
differentiated in adults. Laboratory techniques for viral identification have
advanced without substantial literature to suggest how a dermatologist ought to
conduct a cost-effective and diagnostic viral panel. Certain clinical features
such as petechiae, vesicles, and dusky macular or morbilliform exanthems point
strongly toward a viral exanthem. Differentiation of drug and viral causes of
morbilliform eruptions has proven difficult. It is possible that with further
diagnostic refinement that unnecessary and fruitless workups of an exanthem and
unneeded discontinuation of drugs can be avoided. We review viral exanthems based
on clinical features and discuss the available and optimal laboratory techniques
to assist the dermatologist in a targeted workup.
PMID- 28413060
TI - Stuttering treatment and brain research in adults: A still unfolding
relationship.
AB - PURPOSE: Brain imaging and brain stimulation procedures have now been used for
more than two decades to investigate the neural systems that contribute to the
occurrence of stuttering in adults, and to identify processes that might enhance
recovery from stuttering. The purpose of this paper is to review the extent to
which these dual lines of research with adults who stutter have intersected and
whether they are contributing towards the alleviation of this impairment. METHOD:
Several areas of research are reviewed in order to determine whether research on
the neurology of stuttering is showing any potential for advancing the treatment
of this communication disorder: (a) attempts to discover the neurology of
stuttering, (b) neural changes associated with treated recovery, and (c) direct
neural intervention. RESULTS AND CONCLUSIONS: Although much has been learned
about the neural underpinnings of stuttering, little research in any of the
reviewed areas has thus far contributed to the advancement of stuttering
treatment. Much of the research on the neurology of stuttering that does have
therapy potential has been largely driven by a speech-motor model that is
designed to account for the efficacy of fluency-inducing strategies and
strategies that have been shown to yield therapy benefits. Investigations on
methods that will induce neuroplasticity are overdue. Strategies profitable with
other disorders have only occasionally been employed. However, there are signs
that investigations on the neurology of adults who have recovered from stuttering
are slowly being recognized for their potential in this regard.
PMID- 28413061
TI - Mechanical behavior of bulk direct composite versus block composite and lithium
disilicate indirect Class II restorations by CAD-FEM modeling.
AB - OBJECTIVES: To study the influence of resin based and lithium disilicate
materials on the stress and strain distributions in adhesive class II mesio
occlusal-distal (MOD) restorations using numerical finite element analysis (FEA).
To investigate the materials combinations in the restored teeth during
mastication and their ability to relieve stresses. METHODS: One 3D model of a
sound lower molar and three 3D class II MOD cavity models with 95 degrees cavity
margin-angle shapes were modelled. Different material combinations were
simulated: model A, with a 10MUm thick resin bonding layer and a resin composite
bulk filling material; model B, with a 70MUm resin cement with an indirect CAD
CAM resin composite inlay; model C, with a 70MUm thick resin cement with an
indirect lithium disilicate machinable inlay. To simulate polymerization
shrinkage effects in the adhesive layers and bulk fill composite, the thermal
expansion approach was used. Shell elements were employed for representing the
adhesive layers. 3D solid CTETRA elements with four grid points were employed for
modelling the food bolus and tooth. Slide-type contact elements were used between
the tooth surface and food. A vertical occlusal load of 600 N was applied, and
nodal displacements on the bottom cutting surfaces were constrained in all
directions. All the materials were assumed to be isotropic and elastic and a
static linear analysis was performed. RESULTS: Displacements were different in
models A, B and C. Polymerization shrinkage hardly affected model A and
mastication only partially affected mechanical behavior. Shrinkage stress peaks
were mainly located marginally along the enamel-restoration interface at occlusal
and mesio-distal sites. However, at the internal dentinal walls, stress
distributions were critical with the highest maximum stresses concentrated in the
proximal boxes. In models B and C, shrinkage stress was only produced by the
70MUm thick resin layer, but the magnitudes depended on the Young's modulus (E)
of the inlay materials. Model B mastication behavior (with E=20GPa) was similar
to the sound tooth stress relief pattern. Model B internally showed differences
from the sound tooth model but reduced maximum stresses than model A and
partially than model C. Model C (with E=70GPa) behaved similarly to model B with
well redistributed stresses at the occlusal margins and the lateral sides with
higher stress concentrations in the proximal boxes. Models B and C showed a more
favorable performance than model A with elastic biomechanics similar to the sound
tooth model. SIGNIFICANCE: Bulk filling resin composite with 1% linear
polymerization shrinkage negatively affected the mechanical behavior of class II
MOD restored teeth. Class II MOD direct resin composite showed greater potential
for damage because of higher internal and marginal stress evolution during resin
polymerization shrinkage. With a large class II MOD cavity an indirect composite
or a lithium disilicate inlay restoration may provide a mechanical response close
to that of a sound tooth.
PMID- 28413062
TI - Assessment of mucosal integrity by quantifying neutrophil granulocyte influx in
murine models of acute intestinal injury.
AB - Intact epithelial body surfaces represent physical barriers which protect the
organism from invading pathogens and loss of nutrients. Barrier malfunction is
closely linked to disorders such as inflammatory bowel disease and graft-versus
host disease. In fact, several pharmacological or radiobiological therapeutic
strategies have side effects that affect epithelial surfaces. In this context,
assays that accurately assess epithelial barrier integrity in patients and animal
models are crucial to create a better understanding of the mechanisms leading to
disease or limiting therapeutic approaches due to barrier disruption. Here, we
tested the ability of the widely used FITC-dextran intestinal permeability
analysis to evaluate loss of intestinal barrier integrity in different murine
models of gut mucosal damage and established influx of neutrophil granulocytes
into the intestinal lamina propria (LP) as an alternative approach. We
demonstrate that the sensitivity and specificity of FITC-dextran intestinal
permeability analysis is relatively low: Although it did represent severe forms
of mucosal damage due to intensive conditioning therapy (high doses of either
total body irradiation (TBI) or chemotherapy) or after conditioning and
allogeneic stem cell transplantation, it did not recognize less severe forms of
damage as after lower doses of TBI or chemotherapy alone. In addition,
discrimination of untreated from irradiated mice by differences in FITC-dextran
translocation was not exact. In contrast, influx of neutrophil granulocytes into
the intestinal LP, which reflects immune activation due to translocation of
microbes and microbial products during intestinal barrier breech, quantitatively
correlated with the severity of intestinal barrier damage. It accurately
represented both severe and less severe forms of intestinal damage as after high
or lower dose TBI or chemotherapy and correctly discriminated treated from
untreated animals. Taken together, we demonstrate the limitations of FITC-dextran
intestinal permeability analysis and identify intestinal neutrophil influx as a
powerful additional tool to measure breakdown of intestinal barrier function.
PMID- 28413063
TI - Amniotic membrane application for the healing of chronic wounds and ulcers.
AB - Wound healing usually follows a predictable sequence and prognosis of events. Its
evolutionary process is the result of a complicated interaction between patient
related factors, the wound, the treatment used and the skills and knowledge of
the professionals who treat them. Only through a meticulous initial assessment of
the wound is it possible to identify the factors that contribute to its
complexity. The challenge for professionals will be to implement efficient
therapies at the right time and in the most cost-efficient way in order to reduce
associated problems, treat the symptoms and expectations of the patients and
achieve adequate wound healing whenever possible. This is particularly evident in
big chronic wounds with considerable tissue loss, which become senescent in the
process of inflammation or proliferation losing the ability to epithelialize.
Generally, chronic wounds do not respond to current treatments, therefore they
need special interventions. AM is a tissue of particular interest as a biological
dressing and it has well-documented reepithelialization effects which are in part
related to its capacity to synthesize and release biological active factors. Our
studies have demonstrated that amniotic membrane (AM) is able to induce
epithelialization in chronic wounds that were unable to epithelialize. AM induces
several signaling pathways that are involved in cell migration and/or
proliferation. Additionally, AM is able to selectively antagonize the anti
proliferative effect of transforming growth factor-beta (TGF-beta) by modifying
the genetic program that TGF-beta induces on keratinocytes. The combined effect
of AM on keratinocytes, promoting cell proliferation/migration and antagonizing
the effect of TGF-beta is the perfect combination, allowing chronic wounds to
move out of their non-healing state and progress into epithelialization.
PMID- 28413064
TI - Systemic sclerosis.
AB - Systemic sclerosis, also called scleroderma, is an immune-mediated rheumatic
disease that is characterised by fibrosis of the skin and internal organs and
vasculopathy. Although systemic sclerosis is uncommon, it has a high morbidity
and mortality. Improved understanding of systemic sclerosis has allowed better
management of the disease, including improved classification and more systematic
assessment and follow-up. Additionally, treatments for specific complications
have emerged and a growing evidence base supports the use of immune suppression
for the treatment of skin and lung fibrosis. Some manifestations of the disease,
such as scleroderma renal crisis, pulmonary arterial hypertension, digital
ulceration, and gastro-oesophageal reflux, are now treatable. However, the burden
of non-lethal complications associated with systemic sclerosis is substantial and
is likely to become more of a challenge. Here, we review the clinical features of
systemic sclerosis and describe the best practice approaches for its management.
Furthermore, we identify future areas for development.
PMID- 28413065
TI - Outcome of low profile mesh plate in management of comminuted displaced fracture
patella.
AB - PURPOSE: To assess the clinical results of using mesh plate in management of
displaced comminuted fracture patella. PATIENTS AND METHODS: Between January 2014
and October 2015, nine patients with closed displaced comminuted fracture patella
were fixed using mesh plate and 2mm mini screws. RESULTS: All fractures united
after an average of 10 weeks. At final follow-up of an average 19.6 months,
average postoperative Lysholm score was 89.1+/-4.9, and average Postoperative
Bostman scale was 27.2+/-3.1. No hardware related complications were recorded.
CONCLUSION: Low profile mesh plate is a good option in management of comminuted
fracture patella with good clinical outcome. This new surgical technique may be
particularly useful in comminuted fractures when patellectomy would otherwise be
considered.
PMID- 28413066
TI - Temporary portal vein embolization is as efficient as permanent portal vein
embolization in mice.
AB - BACKGROUND: Temporary portal vein embolization may be a safe alternative to
permanent portal vein embolization. Such a new approach could be applied in
living-related liver transplantation to increase graft volume before procurement.
The impact of temporary portal vein embolization on occluded liver after
recanalization, however, has never been assessed. Using a mouse model of
temporary portal vein embolization, we investigated (1) the efficiency of
temporary portal vein embolization in inducing nonoccluded liver hypertrophy and
(2) the regeneration potential and functional recovery of embolized liver after
recanalization. METHODS: Selected portal vein branches were occluded using
gelfoam powder (temporary portal vein embolization) or embospheres (permanent
portal vein embolization), n = 5/group. Magnetic resonance volumetry and
angiography were used to determine volumes of the liver lobe and portal vein
branch recanalization. In order to assess the functional and regenerative
capacity of occluded liver lobes, nonoccluded lobes were resected 14 days
(timespan of complete portal vein recanalization) after temporary portal vein
embolization or permanent portal vein embolization. Subsequently, RNA sequencing
was performed to compare the signaling pathways of early liver regeneration among
the groups. RESULTS: Hypertrophy of nonoccluded lobes 30 days after temporary
portal vein embolization and permanent portal vein embolization was similar (103
+/- 26% and 129 +/- 13%, P = .11). Temporary occluded lobes increased their
volumes after nonoccluded lobes resection, reaching similar liver-to-body-weight
ratios and similar functional capacity after 7 days compared with partial
hepatectomy controls (4 +/- 1% vs 4 +/- 1%, P = .22). Partial hepatectomy
activated similar signaling pathways in temporary occluded and native liver.
CONCLUSION: Temporary portal vein embolization induces hypertrophy of
contralateral liver lobes similarly to permanent portal vein embolization in
mice. This experimental work suggests that temporary portal vein embolization may
be considered as a possibility in living liver donation, because regenerative and
functional capacities are preserved in the embolized liver after recanalization
in mice.
PMID- 28413067
TI - Contraception and menstrual bleeding during venous thromboembolism treatment:
Does current practice reflect expert option?
PMID- 28413069
TI - Improving the upper-limb force feasible set evaluation by muscles maximal
isometric force identification and cocontraction factors.
AB - In order to improve the evaluation of the force feasible set (FFS) of the upper
limb which is of great interest in the biomechanics field, this study proposes
two additional techniques. The first one is based on the identification of the
maximal isometric force (MIF) of Hill-based muscles models from sEMG and
isometric force measurements at the hand. The second one considers muscles
cocontraction. The FFS was computed with an upper-limb musculoskeletal model in
three different cases. The first one (M1) considered binary muscular activation
and a simple MIF scaling method based on the weight and muscle length of the
subject. The second one (M2) introduces cocontraction factors determined from
sEMG. The third one (M3) considers the cocontraction factors and the MIF
identification. Finally, M1, M2 and M3 are compared with end-effector force
measurement. M3 outperforms the two other methods on FFS prediction demonstrating
the validity and the usefulness of MIF identification and the consideration of
the cocontraction factors.
PMID- 28413068
TI - Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices.
AB - Adult tissue stem cells (SCs) reside in niches, which, through intercellular
contacts and signaling, influence SC behavior. Once activated, SCs typically give
rise to short-lived transit-amplifying cells (TACs), which then progress to
differentiate into their lineages. Here, using single-cell RNA-seq, we unearth
unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots
of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces,
where progenitors display molecular signatures reflective of spatially distinct
local signals and intercellular interactions. Using lineage tracing, temporal
single-cell analyses, and chromatin landscaping, we show that SC plasticity
becomes restricted in a sequentially and spatially choreographed program,
culminating in seven spatially arranged unilineage progenitors within TACs of
mature follicles. By compartmentalizing SCs into micro-niches, tissues gain
precise control over morphogenesis and regeneration: some progenitors specify
lineages immediately, whereas others retain potency, preserving self-renewing
features established early while progressively restricting lineages as they
experience dynamic changes in microenvironment.
PMID- 28413070
TI - Processing graspable object images and their nouns is impaired in Parkinson's
disease patients.
AB - According to embodiment, the recruitment of the motor system is necessary to
process language material expressing a motor content. Coherently, an impairment
of the motor system should affect the capacity to process language items with a
motor content. The aim of the present study was to assess the capacity to process
graspable objects and their nouns in Parkinson's disease (PD) patients and
healthy controls. Participants saw photos and nouns depicting graspable and non
graspable objects. Scrambled images and pseudo-words served as control stimuli.
At 150 msec after stimulus presentation, they had to respond when the stimulus
referred to a real object, and refrain from responding when it was meaningless
(go-no go paradigm). In the control group, participants gave slower motor
responses for stimuli (both photos and nouns) related to graspable objects as
compared to non-graspable ones. This in keeping with data obtained in a previous
study with young healthy participants. In the PD group, motor responses were
similar for both graspable and non-graspable items. Moreover, error number was
significantly greater than in controls. These findings support the notion that
when the motor circuits are lesioned, like in PD, patients do not show the
typical modulation of motor responses and have troubles in processing graspable
objects and their nouns.
PMID- 28413071
TI - Performance of ultra-low-dose CT for the evaluation of coronary calcification: a
direct comparison with coronary calcium score.
AB - AIM: To evaluate the diagnostic performance of ultra-low-dose computed tomography
(ULDCT) in comparison to standard coronary calcium score (CCS) acquisition for
the evaluation of coronary artery calcification (CAC). MATERIALS AND METHODS:
Standard CCS acquisition and ULDCT were performed in patients referred for
coronary CT angiography for the evaluation of coronary artery disease. CAC in
ULDCT was graded subjectively using a four-point scale (from 0, no calcification,
to 3, severe calcification) for the complete study and for each individual
coronary segment. The summation of all individual coronary segment scores
generated an ULDCT total CAC score. ULDCT results were compared to standard
Agatston score and sensitivity and specificity of ULDCT were calculated. RESULTS:
CCS and ULDCT were performed in 74 patients, with a mean DLP of 77.7 mGy.cm (+/
12.1) and 9.3 mGy.cm (+/-0.6), respectively (p<0.001). Coronary calcification was
detected in 47 patients (63.5%) in standard CCS acquisition (median Agatston
score of 41; interquartile range [IQR]:0263), in comparison to 42 patients
(56.8%) in ULDCT (p<0.001). The sensitivity and specificity of the ULDCT total
CAC score >=1 was 80.9% and 85.2%, respectively, with an accuracy of 82.4%. The
area under the receiver operating characteristic curve for the presence of CAC
was 0.87. CONCLUSION: ULDCT shows good sensitivity, specificity, and overall
accuracy for the detection of coronary calcification with a markedly lower
radiation dose in comparison to CCS. ULDCT is unlikely to miss coronary
calcification in individuals with at least moderate calcium load (Agatston score
>100).
PMID- 28413072
TI - Progressive regression of intracranial arteriovenous malformations after Onyx
embolization.
AB - Progressive regression of cerebral arteriovenous malformations (AVMs) is a rare
phenomenon that may occur spontaneously or after previous surgical or
endovascular incomplete obliteration. We present two cases of AVMs occluded
partially with Onyx followed by the unexpected cure of the lesions with the
angiographic evidences as well as multiannual follow-up.
PMID- 28413073
TI - Effects of short-term weathering on the stable carbon isotope compositions of
crude oils and fuel oils.
AB - A short-term simulated weathering experiment was performed on two crude oils and
two heavy fuel oils under natural conditions to evaluate the effects of natural
weathering processes by using gas chromatography-mass spectrometry combined with
gas chromatography-isotopic ratio mass spectrometry. The results of diagnostic
ratios of n-alkanes show that only odd to even predominance (OEP1, OPE2) and
carbon preference index (CPI) remain stabilized during the 28 d weathering
process, but they cannot effectively distinguish the four types of oils.
Statistical analyses based on paired sample t-test and principal component
analysis (PCA) revealed that stable carbon isotope compositions of n-alkanes in
the four studied oils have no significant changes over the weathering time, and
that the carbon isotope discrimination (Deltadelta13C) of n-alkanes is <30/00. We
have provided evidence that the stable carbon isotope compositions of n-alkanes
compared to n-alkanes diagnostic ratios significantly improve the efficiency and
fidelity of the oil fingerprint identification.
PMID- 28413074
TI - Long-term outcomes of extracorporeal membrane oxygenation support for
postcardiotomy shock.
AB - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a widely used technique
for treating postcardiotomy cardiogenic shock (PCS); however, no study has
compared the long-term outcomes of patients who receive ECMO support for PCS with
those of the general population post cardiac surgery. METHODS: A total of 1141
patients who received ECMO after cardiac surgery between 2000 and 2011 were
identified by using the Taiwan National Health Insurance Research Database. For
each patient, we matched 5 non-ECMO patients who had undergone cardiac surgery by
using propensity scores calculated for age, sex, 12 comorbid diseases, Charlson
score, hospital level, type of cardiac surgery, and year of index
hospitalization. The outcomes included all-cause mortality, readmission for any
cause, and medical expenditure. RESULTS: The incidence of ECMO use after cardiac
surgery in Taiwan was 1.91%. The ECMO group had a significantly higher risk of in
hospital mortality than did the non-ECMO group (61.7% vs 6.8%, odds ratio 22.34,
95% confidence interval 19.06-26.18). The risks of all-cause mortality and first
readmission for any cause were greater in the ECMO group than that in the control
group (P < .001, P < .001) in the first year, whereas no difference was observed
after the first year of follow-up (P = .209, P = .474). Similar results were
observed regarding the medical expenditure of admission after index admission
discharge. CONCLUSIONS: Patients receiving ECMO for PCS had similar outcomes to
those of the non-ECMO group after the first year of follow-up despite
significantly poor outcomes during the in-hospital course.
PMID- 28413075
TI - Abrasion and blunt tissue trauma study of a novel flexible robotic system in the
porcine model.
AB - OBJECTIVES: The objective of this study was to determine if a flexible robotic
system caused increased tissue reaction when accessing the oropharynx and
hypopharynx compared to intubation controls in only 2 scenarios: high speed
tissue impact and multiple unit insertions and retractions. The data obtained
were submitted as part of the entirety of information submitted for FDA approval.
METHODS: This study consisted of 5 groups of Yorkshire pigs (2 animals per
group). On Day 0, all animals were intubated. For group 1 (control), a second
endotracheal tube was advanced to just above the vocal cords. In abrasion groups
2 and 3, the flexible robotic system was advanced against the oropharyngeal and
hypopharyngeal tissues, respectively. In blunt trauma groups 4 and 5, the
flexible robotic system was advanced at maximum speed (22mm/s) to collide with
oropharyngeal and hypopharyngeal tissues, respectively. Pre- and post-procedure
endoscopic assessments of tissue reaction were performed daily for 4 days. An
independent reviewer graded tissue reaction using a 0-3 point scale. RESULTS:
Tissue reaction scores at each observation time point for all test groups were
less than or equal to control scores except for one instance of moderate scoring
(2 out of 3) on Day 2 for an animal in the blunt trauma group where reaction was
likely intubation-related rather than device impact related. Otherwise, all
flexible robotic system-treated animal scores were less than 1 by Day 4.
CONCLUSIONS: In this limited study, the flexrobotic system afforded surgical
access to the oropharynx and hypopharynx without an increased level of abrasion
or tissue trauma when compared to intubation alone.
PMID- 28413076
TI - Detection of endolymphatic hydrops using traditional MR imaging sequences.
AB - PURPOSE: The purpose of this study was to determine whether Meniere's disease
(MD) produces endolymphatic cavity size changes that are detectable using
unenhanced high-resolution T2-weighted MRI. MATERIALS & METHODS: This
retrospective case-control study included patients with documented MD who had a
high-resolution T2-weighted or steady-state free procession MRI of the temporal
bones within one month of diagnosis, between 2002 and 2015. Patients were
compared to age- and sex- matched controls. Cross sectional area, length, and
width of the vestibule and utricle were measured in both ears along with the
width of the basal turn of the cochlea and its endolymphatic space. Absolute
measurements and ratios of endolymph to perilymph were compared between affected,
contralateral, and control ears using analysis of variance and post-hoc pairwise
comparisons. RESULTS: Eighty-five case-control pairs were enrolled. Mean utricle
areas for affected, contralateral, and control ears were 0.038cm2, 0.037cm2, and
0.033cm2. Mean area ratios for affected, contralateral, and control ears were
0.32, 0.32, and 0.29. There was a statistically significant difference between
groups for these two variables; post-hoc comparisons revealed no difference
between affected and contralateral ears in Meniere's patients, while ears in
control patients were different from the ears of patients with MD. All other
measurements failed to show significant differences. CONCLUSIONS: Enlargement of
the endolymphatic cavity can be detected using non-contrast T2-weighted MRI. MRI,
using existing protocols, can be a useful diagnostic tool for the evaluation of
MD, and intratympanic or delayed intravenous contrast may be unnecessary for this
diagnosis.
PMID- 28413077
TI - Trichomonosis outbreak in a flock of canaries (Serinus canaria f. domestica)
caused by a finch epidemic strain of Trichomonas gallinae.
AB - In the present paper, an outbreak of trichomonosis in a flock of 15 breeding
pairs of canaries is described. Trichomonosis was diagnosed on characteristic
clinical signs, microscopic examination of crop/esophageal swabs, gross pathology
and histopathology. Trichomonads were successfully grown in culture media and
were characterized by multi-locus sequence typing. The three genomic loci ITS1
5.8S-ITS2, 18S rRNA and Fe-hydrogenase were analyzed. Molecular characterization
confirmed the finch trichomonosis strain, identical to the strain that caused
emerging disease in free-living passerine birds in Europe. Flock treatment with
metronidazole (200mg/L) in drinking water for 5days was partially effective.
After individual treatment with oral application of metronidazole (20mg/kg SID)
for 5days no further clinical signs were observed in the flock over next 30
months.
PMID- 28413078
TI - Evaluation of immunochromatographic test (ICT) strips for the serological
detection of Babesia bovis and Babesia bigemina infection in cattle from Western
Java, Indonesia.
AB - Three types of immunochromatographic test (ICT) strips were prepared for the
detection of an antibody response against spherical body protein 4 (SBP-4) of
Babesia bovis (bovICT), C-terminal-truncated rhoptry-associated protein 1
(rRAP1/CT17) of B. bigemina (bigICT), and the combination of both proteins (dual
ICT). The evaluation of their performance was conducted using a confirmed
positive and negative serum panel for B. bovis and B. bigemina. Together with
ELISA, the ICT strips were applied to determine the seroprevalence of bovine
babesiosis in Western Java, Indonesia. Among 991 serum samples, 28.4%, 25.3%, and
24.5% of cattle were detected to be seropositive to B. bovis infection using
ELISA, bovICT, and dual-ICT, respectively. B. bigemina seropositive was detected
in 27.1%, 24.2%, and 22.8% of samples using ELISA, bigICT, and dual-ICT,
respectively. The comparison of ICT strips and ELISA results using field serum
samples showed good agreement with Kappa values >0.7 between all methods The
application of ICT strips is preferable in the field situations where rapid
diagnosis is required. Furthermore, the data showed the current seroprevalence of
bovine babesiosis in Western Java, Indonesia, and efficient control strategies
are needed to reduce economic losses due to the disease.
PMID- 28413079
TI - Mexican consensus on dyspepsia.
AB - Since the publication of the 2007 dyspepsia guidelines of the Asociacion Mexicana
de Gastroenterologia, there have been significant advances in the knowledge of
this disease. A systematic search of the literature in PubMed (01/2007 to
06/2016) was carried out to review and update the 2007 guidelines and to provide
new evidence-based recommendations. All high-quality articles in Spanish and
English were included. Statements were formulated and voted upon using the Delphi
method. The level of evidence and strength of recommendation of each statement
were established according to the GRADE system. Thirty-one statements were
formulated, voted upon, and graded. New definition, classification, epidemiology,
and pathophysiology data were provided and include the following information:
Endoscopy should be carried out in cases of uninvestigated dyspepsia when there
are alarm symptoms or no response to treatment. Gastric and duodenal biopsies can
confirm Helicobacter pylori infection and rule out celiac disease, respectively.
Establishing a strong doctor-patient relationship, as well as dietary and
lifestyle changes, are useful initial measures. H2-blockers, proton-pump
inhibitors, prokinetics, and antidepressants are effective pharmacologic
therapies. H.pylori eradication may be effective in a subgroup of patients. There
is no evidence that complementary and alternative therapies are beneficial, with
the exception of Iberogast and rikkunshito, nor is there evidence on the
usefulness of prebiotics, probiotics, or psychologic therapies. The new consensus
statements on dyspepsia provide guidelines based on up-to-date evidence. A
discussion, level of evidence, and strength of recommendation are presented for
each statement.
PMID- 28413080
TI - Effect of oral exposure to artificially weathered Deepwater Horizon crude oil on
blood chemistries, hepatic antioxidant enzyme activities, organ weights and
histopathology in western sandpipers (Calidris mauri).
AB - Shorebirds were among birds exposed to Mississippi Canyon 252 (MC252) crude oil
during the 2010 Deep Water Horizon (DWH) oil spill in the Gulf of Mexico. The
western sandpiper (Calidris mauri) was chosen as one of four species for initial
oral dosing studies conducted under Phase 2 of the avian toxicity studies for the
DWH Natural Resource Damage Assessment (NRDA). Thirty western sandpipers were
assigned to one of three treatment groups, 10 birds per group. The control group
was sham gavaged and the treatment groups were gavaged with 1 or 5mL oil kg bw-1
daily for 20 days. Periodic blood samples for hemoglobin measurements were
collected during the trial. A final blood sample used to determine hemoglobin
concentration in addition to complete blood counts, plasma clinical chemistries,
haptoglobin concentration and plasma electrophoresis was collected when birds
were euthanized and necropsied on day 21. Tissues were removed, weighed and
processed for subsequent histopathological evaluation. There were numerical
decreases in hemoglobin concentrations in oil-dosed birds over the 21-day trial,
but values were not significantly different compared to controls on day 21. There
were no significant differences between controls and oiled birds in complete
blood counts, plasma chemistries, haptoglobin concentration, and plasma
electrophoresis endpoints. Of the hepatic oxidative stress endpoints assessed,
the total antioxidant capacity assessment (Trolox equivalents) for the control
group was lower compared to the 1mL oil kg bw-1 group. Absolute liver weights in
the 5mL oil kg bw-1 group were significantly greater compared to controls. While
not conclusive, the numerical decrease in hemoglobin concentration and
significant increase in absolute liver weight are consistent with exposure to
oil. Histological changes in the adrenal gland could be considered a non-specific
indicator of stress resulting from exposure to oil. It is possible that the
quantity of oil absorbed was not sufficient to induce clearly evident hemolytic
anemia or that the western sandpiper is relatively insensitive to ingested oil.
PMID- 28413081
TI - How can Video-Based Sessions Improve E-Learning of Respiratory Physiology?
PMID- 28413082
TI - Primary Sjogren Syndrome With Pleural Effusion.
PMID- 28413083
TI - A novel nuclear xenobiotic receptors (AhR/PXR/CAR)-mediated mechanism of DEHP
induced cerebellar toxicity in quails (Coturnix japonica) via disrupting CYP
enzyme system homeostasis.
AB - Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife
animal and human through environment and food chain, including the effect of
brain development and impacted neurobehavioral outcomes. However, DEHP exposure
caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted
potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500
and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral
abnormality and cerebellar histopathological alternation were observed in DEHP
induced quails. DEHP exposure increased the contents of total Cytochrome P450s
(CYPs) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c
reductase (NCR) and aniline-4-hydeoxylase (AH) in quail cerebellum. The
expression of nuclear xenobiotic receptors (NXRs) and the transcriptions of CYP
enzyme isoforms were also influenced in cerebellum by DEHP exposure. These
results suggested that DEHP exposure caused the toxic effects of quail
cerebellum. DEHP exposure disrupted the cerebellar CYP enzyme system homeostasis
via affecting the transcription of CYP enzyme isoforms. The cerebellar P450arom
and CYP3A4 might be biomarkers in evaluating the neurotoxicity of DEHP in bird.
Finally, this study provided new evidence that DEHP-induced toxic effect of quail
cerebellum was associated with activating the NXRs responses and disrupting the
CYP enzyme system homeostasis.
PMID- 28413085
TI - Letter to Editor: A Case of Election-Induced Shingles?
PMID- 28413084
TI - Brominated dioxins/furans and hydroxylated polybrominated diphenyl ethers:
Occurrences in commercial 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and 2,4,6
tribromophenol, and formation during synthesis of BTBPE.
AB - Polybrominated dibenzo-p-dioxins (PBDDs) and hydroxylated polybrominated diphenyl
ethers (OH-PBDEs) can be formed from bromophenols (BPs) by thermal degradation,
biosynthesis or phototransformation. However, it is unknown whether PBDDs and OH
PBDEs can be formed during the chemical production processes that utilize BPs as
raw materials. 2,4,6-tribromophenol (2,4,6-TBP) is an important raw material for
the synthesis of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), a novel brominated
flame retardant. In this study, PBDDs, polybrominated dibenzofurans (PBDFs) and
OH-PBDEs have been identified and quantified in commercially available BTBPE and
2,4,6-TBP. Furthermore, their formation as unintentional by-products during the
laboratory synthesis of BTBPE from 2,4,6-TBP and 1,2-dibromoethane in the
presence of sodium carbonate has also been investigated. 2,3,7,8-substituted
PBDDs and PBDFs (2,3,7,8-PBDD/Fs) were undetectable in commercial samples of
BTBPE and present in low levels (nanogram per gram) in 2,4,6-TBP. Two
tetrabrominated dibenzo-p-dioxins (TeBDDs), namely 1,3,6,8- and 1,3,7,9-TeBDD,
and three hydroxylated pentabrominated diphenyl ethers (OH-pentaBDEs), namely 4'
OH-BDE121, 2'-OH-BDE121, and 6'-OH-BDE100, were identified or tentatively
identified, and quantitatively estimated to be at concentrations in the range of
undetectable to several thousands of nanograms per gram in commercial BTBPE and
2,4,6-TBP. TeBDDs and OH-pentaBDEs were formed as by-products from 2,4,6-TBP
during BTBPE synthesis. Further studies need to be conducted in order to
determine whether PBDD/Fs and OH-PBDEs are also formed during the industrial
synthesis of other chemical compounds that utilize BPs as raw materials or
intermediates.
PMID- 28413086
TI - Clinically Feasible Stratification of 3-Year Chronic Disease Risk in Primary
Care: The Mental Health Integration Risk Score.
AB - BACKGROUND: Depression is a common illness that imposes a disproportionately
large health burden. Depression is generally associated with a higher prevalence
of chronic disease risk factors and may contribute to higher chronic disease
risk. OBJECTIVE: This study aimed to create and validate sex-specific Mental
Health Integration Risk Scores (MHIRS) that predict 3-year chronic disease
diagnosis. METHODS: MHIRS was created to predict the first diagnosis of any of
the 10 chronic diseases in patients completing a Patient Health Questionnaire-9
Depression Survey who were free at baseline from those 10 chronic disease
diagnoses. MHIRS used sex-specific weightings of Patient Health Questionnaire 9
results, age, and components of the complete metabolic profile and complete blood
count in randomly chosen derivation (70%) and validation (30%) groups. RESULTS:
Among females (N = 10,162, age: 48 +/- 16), c-statistics for the composite
chronic disease end point were 0.746 (0.725, 0.767) for the derivation group and
0.717 (0.682, 0.753) for the validation group, whereas males (N = 4615, age: 48
+/- 15) had 0.755 (0.727, 0.783) and 0.742 (0.702, 0.782). In the validation
group, MHIRS strata of low-, moderate-, and high-risk categories had hazard
ratios (HR) for any 3-year chronic disease diagnosis among females of HR = 3.42
for moderate vs low and HR = 9.75 for high vs low, whereas males had HR = 4.80
and HR = 10.68, respectively (all p < 0.0001). CONCLUSION: A clinical decision
tool comprised by depression severity and common laboratory tests, and MHIRS
provides very good stratification of a 3-year chronic disease diagnosis. Designed
to be calculated electronically by an electronic health record, MHIRS can be
efficiently obtained by clinicians to identify patients at higher chronic disease
risk who require further evaluation and more precise clinical management.
PMID- 28413087
TI - Does Social Support Moderate the Association Among Major Depression, Generalized
Anxiety Disorder, and Functional Disability in Adults With Diabetes?
AB - BACKGROUND: Diabetes requires complex self-management routines to prevent the
development of functional disability. Relative to people without diabetes, those
with diabetes are more likely to have comorbid major depressive disorder (MDD)
and generalized anxiety disorder (GAD), which also increase the likelihood of
functional disability. Social support is associated with positive health outcomes
in people with comorbid diabetes and mental disorders and may serve as a buffer
against functional disability, though this possibility has yet to be examined.
OBJECTIVES: This study examined whether social support moderates the association
between MDD or GAD and functional disability in adults with diabetes. Adults with
MDD or GAD were expected to report greater disability than those without MDD or
GAD. This association was expected to be stronger in people reporting lower
social support relative to those reporting higher social support. METHODS: Data
came from the cross-sectional 2012 Canadian Community Health Survey-Mental Health
(n = 1764). Diabetes status, social support, and functional disability were
assessed via self-report; past-year MDD and GAD were assessed with structured
diagnostic interviews. RESULTS: Linear regression analyses, conducted separately
for MDD and GAD, indicated main effects of past-year MDD and GAD, such that those
with a mental disorder reported greater functional disability than those without
a mental disorder. Social support did not moderate the associations between
either MDD and functional disability or GAD and functional disability.
CONCLUSIONS: In this nationally representative population study, both MDD and GAD
predicted greater functional disability in adults with diabetes. Social support,
however, did not moderate these associations.
PMID- 28413088
TI - A Retrospective Analysis of Neurocognitive Impairment in Older Patients With Burn
Injuries.
AB - BACKGROUND: Older adults comprise a growing proportion of the United States
population that is at risk for burns. However, few studies have examined
cognitive function in this patient population. OBJECTIVE: The purpose of this
study was to measure the prevalence and incidence of dementia and delirium in
older adults admitted for burn injuries. METHODS: This was an Institutional
Review Board-approved, retrospective study of all patients 65 years and older
admitted to the University of North Carolina Jaycee Burn Center from 2005-2015.
Data extracted from the medical records included patient demographics,
characteristics of the burn injury, incidence of delirium, incidence of
psychiatric consultation, diagnosis of dementia, disposition, and mortality. The
primary outcomes of interest were the prevalence and incidence of dementia and
delirium. Secondary outcomes included length of stay and cost of hospitalization.
RESULTS: A total of 392 patients were included. These patients had a median age
of 74 years and a median total body surface area burn of 7%. On admission, 44
patients (11%) had a diagnosis of dementia. An additional 28 patients were
diagnosed with dementia during hospitalization for a total of 72 patients (18%);
154 patients (39%) were diagnosed with delirium. After controlling for burn
severity, dementia and delirium were significantly associated with length of
stay, incidence of psychiatry consultation, and discharge to a skilled nursing
facility. CONCLUSIONS: Physicians should have high suspicion for dementia and
delirium in older patients admitted for burn injuries. Dementia and delirium are
associated with morbidity in older patients with burn injuries.
PMID- 28413089
TI - Loperamide Abuse and Life-Threatening Arrhythmias: A Case Report and Literature
Review.
PMID- 28413090
TI - Serum Valproic Acid Levels During Initial Conversion of Antituberculoid Therapy
in Bipolar Mania: A Case Report and Literature Review.
PMID- 28413092
TI - Resisting the Urge to Act: DREADDS Modifying Habits: (Trends in Neurosciences 40,
61-62; 2017).
PMID- 28413091
TI - "What We Have Here is a Failure to Communicate": Association of Preferred
Language With the Rate of Psychiatric Consultation.
AB - BACKGROUND: In the United States, people with limited English proficiency (LEP)
receive poorer medical care than those proficient in English. Few studies
demonstrate how linguistic barriers complicate psychiatric care; in consultation
liaison (C-L) psychiatry, there are no published data about care disparities for
patients with LEP or for whom English is not the preferred language (PL).
OBJECTIVE: We sought to determine if PL affects the psychiatric consultation
rate. METHODS: Among adult patients admitted during 1 year to a large urban
academic medical center, we compared psychiatric consultation rates in English PL
patients with non-English PL patients. PL was ascertained from demographics
during the medical record. The occurrence of psychiatric consultation was
ascertained from C-L service logs. RESULTS: There were 54,534 admissions: the no
consultation group (N = 53,196) and the consultation group (N = 1,398). English
as PL was more common in the consult group (72.0% of consult group, 62.0% of no
consult group, chi2 = 92.98, p < 0.0001). Spanish speakers were underrepresented
in the consult group (14.2% of consult, 25.8% of no-consult, chi2 = 98.78, p <
0.0001). CONCLUSION: Primary teams requested more consultations for patients
whose PL was English than for patients with other PLs, suggesting that
psychiatric needs of patients with non-English PL may be unaddressed. This is the
first study to demonstrate a disproportionately low rate of general hospital
psychiatric consultations in this population. Further study is necessary to
confirm and understand this disparity. We recommend routine use of professional
interpreters and low threshold for consultation in patients with non-English PL.
PMID- 28413093
TI - [Thrombotic thrombocytopenia purpura in Martinique: Retrospective study between
2008 and 2015].
AB - INTRODUCTION: Some studies suggest that thrombotic thrombocytopenic purpura (TTP)
occurs more often in African Americans. However there is low evidence for this in
the literature. The aim of our study was to describe the clinical and biological
characteristics of TTP in the Afro-Caribbean population of Martinique. METHODS:
We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France
hospital between 2008, January 1st and 2015, December 31st. Diagnosis was
confirmed if ADAMTS-13 activity was<10 %. RESULTS: Ten patients were included,
corresponding to an average annual incidence of 3.2 cases/year/million
individuals. None of the patient presented with the association of the five
characteristic features of TTP. Microangiopathic haemolytic anaemia and severe
peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to
diagnosis. There was no kidney involvement in 90 % of all patients, but severe
neurological manifestations occurred in 70 %. Classical management including
corticosteroids and plasma exchanges allowed clinical remission in 6 out of the
10 cases. If necessary, rituximab or cyclophosphamide was used. The overall
survival rate was 90 %. CONCLUSION: In Martinique, the incidence of TTP is twice
that reported in similar studies in France. Clinical manifestations seem to
differ by more common and more severe neurological involvement. Mortality is low,
in part, due to optimal care.
PMID- 28413094
TI - [Pachymeningitis].
AB - Pachymeningitis is a fibrosing and inflammatory process, which involves the dura
mater. Some pachymeningitis are cranial and induce headaches and cranial nerve
palsies. Others are spinal and responsible for nerve roots or spinal cord
compression. MRI shows contrast enhancement thickening of the dura mater.
Etiologies are infectious (syphilis, tuberculosis, etc.) or inflammatory
(sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease,
idiopathic). Corticosteroids are the main treatment. The use of immunosuppressive
drugs or rituximab is yet to be determined and probably adapted to each etiology.
PMID- 28413095
TI - [The reform of the third cycle of medical studies: What changes for internal
medicine?]
PMID- 28413096
TI - Implementing WebGL and HTML5 in Macromolecular Visualization and Modern Computer
Aided Drug Design.
AB - Web browsers have long been recognized as potential platforms for remote
macromolecule visualization. However, the difficulty in transferring large-scale
data to clients and the lack of native support for hardware-accelerated
applications in the local browser undermine the feasibility of such utilities.
With the introduction of WebGL and HTML5 technologies in recent years, it is now
possible to exploit the power of a graphics-processing unit (GPU) from a browser
without any third-party plugin. Many new tools have been developed for biological
molecule visualization and modern drug discovery. In contrast to traditional
offline tools, real-time computing, interactive data analysis, and cross-platform
analyses feature WebGL- and HTML5-based tools, facilitating biological research
in a more efficient and user-friendly way.
PMID- 28413097
TI - mGlu2/3 Receptor Antagonists as Novel Antidepressants.
AB - Based on the discovery of the robust antidepressant effects of ketamine in
patients with depression, including those with treatment-resistant depression,
agents acting on the glutamatergic system have drawn much attention as potential
novel antidepressants. Among the agents acting on the glutamatergic system,
preclinical data have indicated that the group II metabotropic glutamate (mGlu)
receptors, mGlu2 and mGlu3, are attractive targets for the development of novel
antidepressants. The antidepressant effects of mGlu2/3 receptor antagonists have
been demonstrated in rodent models, and the synaptic and neural mechanisms
underlying the antidepressant effects of these compounds have been investigated.
Furthermore, these findings have indicated the similarities of the antidepressant
effects and of the mechanisms underlying these effects between mGlu2/3 receptor
antagonists and ketamine. Based on the results obtained hitherto, here I discuss
the potential for mGlu2/3 receptor antagonists to be developed as next-generation
antidepressants.
PMID- 28413098
TI - Therapeutic Inhibition of Complement: Well Worth the Risk.
AB - Complement is an integral part of the immune system and protects against
infection. Complement-mediated immunopathology in many autoimmune diseases and
syndromes has led to the therapeutic targeting of complement and to questions
around the safety of complement inhibition. Here; I examine and clarify the risks
associated with complement therapeutics.
PMID- 28413099
TI - Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic
arthritis, and ankylosing spondylitis.
AB - OBJECTIVE: The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed
the most consistent literature to indicate the best strategy for the second-line
biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis
(SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of the
literature to identify English-language articles on efficacy of second-line
biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted
from available randomized, controlled trials, national biologic registries,
national healthcare databases, post-marketing surveys, and open-label
observational studies. RESULTS: Some previously stated variables, including the
patients' preference, the indication for anti-tumor necrosis factor (TNF)
monotherapy in potential childbearing women, and the intravenous route with dose
titration in obese subjects resulted valid for all the three rheumatic
conditions. In RA, golimumab as second-line biologic has the highest level of
evidence in anti-TNF failure. The switching strategy is preferable for responder
patients who experience an adverse event, whereas serious or class-specific side
effects should be managed by the choice of a differently targeted drug. Secondary
inadequate response to etanercept (ETN) should be treated with a biologic agent
other than anti-TNF. After two or more anti-TNF failures, the swapping to a
different mode of action is recommended. Among non-anti-TNF targeted biologics,
to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of
efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing
the first anti-TNF, the switch strategy to a second is advisable, taking in
account the evidence of adalimumab efficacy in patients with uveitis. The
severity of psoriasis, of articular involvement, and the predominance of
enthesitis and/or dactylitis may drive the choice toward ustekinumab or
secukinumab in PsA, and the latter in AS. CONCLUSION: Taking in account the
paucity of controlled trials, second-line biologic therapy may be reasonably
optimized in patients with RA, SpA, and PsA.
PMID- 28413100
TI - Colchicine resistance and intolerance in familial mediterranean fever:
Definition, causes, and alternative treatments.
AB - BACKGROUND: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory
syndrome characterized by recurrent serositis or arthritis attacks and, in some
patients, chronic subclinical inflammation that predisposes to secondary
amyloidosis. Colchicine is the gold standard of treatment, which reduces attack
frequency and amyloidosis risk. However, up to 5% of patients are considered
resistant or inadequately respond to colchicine, and some others cannot tolerate
the side effects of effective doses of colchicine (colchicine intolerant).
METHODS: We examine how the definition of colchicine resistance has evolved along
with various characteristics of colchicine that may help explain unresponsiveness
to the drug. RESULTS: Key factors in assessing colchicine resistance include
attack frequency and severity, levels of acute phase reactants, colchicine dosage
and composition, and treatment compliance. Promising clinical results have been
obtained with biologics targeting interleukin-1 in colchicine-resistant or
intolerant patients with FMF. CONCLUSIONS: These results underscore the need to
identify patients who are not optimally managed with colchicine and who might
therefore benefit from additional biologic therapies.
PMID- 28413101
TI - Evidence for choosing biologic disease-modifying anti-rheumatic drugs in the
treatment of Behcet disease.
PMID- 28413102
TI - [Antibiotic susceptibility of Staphylococcus aureus and Streptococcus pneumoniae
in healthy carrier individuals in primary care in Barcelona area].
AB - INTRODUCTION: The information available on antibiotic resistance patterns are
generally based on specimens from hospitalised individuals. This study was aimed
at evaluating the antibiotic resistance rate of nasal carriage strains of
Staphylococcus aureus and Streptococcus pneumoniae in healthy individuals, in
accordance with age and gender, attended in Primary Care Centres (PCC). DESIGN:
Cross-sectional study. SETTING: Seven PCC in the Barcelona area. PARTICIPANTS:
Healthy nasal carriers aged 4years or more who did not present with any sign of
infectious disease, and had not taken any antibiotic or had been hospitalised in
the previous 3months. MAIN MEASUREMENTS: A total of 3,969 nasal swabs valid for
identification were collected between 2010 and 2011 and were sent to one central
microbiological laboratory for isolation of both pathogens. Resistance to common
antibiotics was determined on the basis of the current European Committee on
Antimicrobial Susceptibility Testing guidelines on cut-off points. RESULTS: The
prevalence of methicillin-resistant S.aureus was 1.3% (95%CI: 0.5-2.1%), with
resistance rates of 87.1% to phenoxymethylpenicillin and 11.6% to azithromycin,
with no significant differences with age and gender. A total of 2.4% (95CI%: 0.1
4.7%) of the pneumococcal strains were highly resistant to both
phenoxymethylpenicillin and macrolides, whereas the highest resistance rates were
to cefaclor (53.3%), followed by tetracycline (20%) and cefuroxime (12.1%).
CONCLUSIONS: These pathogens have lower resistance rates in the community than in
the hospital setting. Primary Care physicians must be more aware of the current
antimicrobial resistance, in order to ensure prudent use of antibiotics.
PMID- 28413103
TI - Do larval types affect genetic connectivity at sea? Testing hypothesis in two
sibling marine gastropods with contrasting larval development.
AB - In marine environments, connectivity among populations of benthic invertebrates
is provided primarily by dispersion of larvae, with the duration of pelagic
larval phase (PLD) supposed to represent one of the major factor affecting
connectivity. In marine gastropods, PLD is linked to specific larval development
types, which may be entirely intracapsular (thus lacking a pelagic dispersal), or
include a short pelagic lecithotrophic or a long planktotrophic phase. In the
present study, we investigated two sibling species of the cosmopolitan
neogastropod genus Columbella (commonly known as dove shells): Columbella
adansoni Menke, 1853, from the Macaronesian Atlantic archipelagos, with
planktotrophic development, and Columbella rustica Linnaeus, 1758, from the
Mediterranean Sea, with intracapsular development. We expected to find
differences between these two sister species, in terms of phylogeographic
structure, levels of genetic diversification and spatial distribution of genetic
diversity, if PLD was actually a relevant factor affecting connectivity. By
analysing the sequence variation at the cytochrome c oxidase subunit I (COI) in
167 specimens of the two species, collected over a comparable geographic range,
we found that Columbella adansoni, the species with planktotrophic development,
and thus longer PLD, showed no phylogeographic structure, lower levels of genetic
diversity, interpopulational variance lower than the intrapopulational one and no
spatial structure in the distribution of the genetic diversity; Columbella
rustica, the species with intracapsular development, thus with evidently lower
dispersal abilities, showed a clear phylogeographic structure, higher levels of
genetic diversity, high interpopulational and low intrapopulational variance, and
a clear signature of global spatial structure in the distribution of the genetic
diversity. Thus, in this study, two sibling species differing almost only in
their larval ecology (and PLD), when compared for their genetic variation showed
patterns supporting the hypothesis that PLD is a major factor affecting genetic
connectivity. Therefore, it seems reasonable to expect that the ecological
attributes of the marine communities - also in terms of the variation in larval
ecology of the species involved - are taken into the due consideration in
conservation actions, like the design of marine protected areas networks.
PMID- 28413104
TI - Altered epiphyte community and sea urchin diet in Posidonia oceanica meadows in
the vicinity of volcanic CO2 vents.
AB - Ocean acidification (OA) predicted for 2100 is expected to shift seagrass
epiphyte communities towards the dominance of more tolerant non-calcifying taxa.
However, little is known about the indirect effects of such changes on food
provision to key seagrass consumers. We found that epiphyte communities of the
seagrass Posidonia oceanica in two naturally acidified sites (i.e. north and
south sides of a volcanic CO2 vent) and in a control site away from the vent at
the Ischia Island (NW Mediterranean Sea) significantly differed in composition
and abundance. Such differences involved a higher abundance of non-calcareous
crustose brown algae and a decline of calcifying polychaetes in both acidified
sites. A lower epiphytic abundance of crustose coralline algae occurred only in
the south side of the vents, thus suggesting that OA may alter epiphyte
assemblages in different ways due to interaction with local factors such as
differential fish herbivory or hydrodynamics. The OA effects on food items
(seagrass, epiphytes, and algae) indirectly propagated into food provision to the
sea urchin Paracentrotus lividus, as reflected by a reduced P. oceanica
exploitation (i.e. less seagrass and calcareous epiphytes in the diet) in favour
of non-calcareous green algae in both vent sites. In contrast, we detected no
difference close and outside the vents neither in the composition of sea urchin
diet nor in the total abundance of calcareous versus non-calcareous taxa. More
research, under realistic scenarios of predicted pH reduction (i.e. <= 0.32 units
of pH by 2100), is still necessary to better understand cascading effects of this
altered urchin exploitation of food resources under acidified conditions on
ecosystem diversity and function.
PMID- 28413105
TI - Investigation of OMNIgene.SPUTUM performance in delayed tuberculosis testing by
smear, culture, and Xpert MTB/RIF assays in Uganda.
AB - OMNIgene.SPUTUM (OM-S) is a sample transport reagent designed to work with all
tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated
sputum samples were assayed in several tests after multiday holds. Raw sputa from
100 patients underwent direct smear microscopy, were manually split and assigned
to the OM-S group [OM-S added at collection (no other processing required) and
tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC)
group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of
collection). Concentrated smear microscopy, Lowenstein Jensen (LJ) culture, and
mycobacteria growth indicator tube (MGIT) culture were performed. For patients
with negative direct smear, a second sample was split, with SOC (raw sputum) and
OM-S portions (sediment) tested in the Xpert MTB/RIF (Xpert) assay. OM-S group
and SOC group results were strongly concordant on all four tests [range, 89%
(MGIT)-97% (Xpert)]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement
with SOC MGIT as reference. OM-S specimens had lower culture contamination rates
(3% vs. 10% LJ; 2% vs. 5% MGIT) but required, on average, 5.6 additional days to
become MGIT-positive. The findings suggest that samples held/transported in OM-S
are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform
comparably to fresh sputum samples. Larger feasibility studies are warranted.
PMID- 28413106
TI - Heterotopic Ossification in adults following a burn: A phenomenological analysis.
AB - Heterotopic Ossification (HO) is a rare but severely debilitating complication
after a burn. Despite there being literature of varying quality explaining the
postulated pathological process, risk factors and treatment for HO, the
individual experiences of adults diagnosed with HO following a burn, remains
unreported. This study sought to explore and describe burn survivors' experiences
of HO to gain a greater understanding of the clinical needs for this unique
patient population. A phenomenological inquiry of five men and one woman selected
through purposeful sampling collected in-depth interviews analysed using
Colaizzi's method of data analysis. Five emergent themes: (1) Early signs and
symptoms, (2) Impact on the rehabilitation journey, (3) The role of the health
care professionals (4) Loss of independence and an increased reliance on others
and, (5) Learning to live with it: uncertainty, hope and adaptation. Eleven
cluster themes were identified, highlighting the meaning of each emergent theme.
These findings describe the significant impact the unique symptomology of HO had
on the physical and psychosocial functioning of participants throughout the
rehabilitation journey. Central to engagement in rehabilitation, is the
participants' desire for autonomy particularly in the domains of living
independently and community re-integration.
PMID- 28413107
TI - Upregulation of MAOA in the hippocampus results in delayed depressive-like
behaviors in burn mice.
AB - OBJECTIVE: To observe depressive-like behavior and hippocampus monoamine oxidase
A (MAOA) changes in burned mice. METHODS: We tested depression and anxiety like
behaviors of burn C57 mice with the sucrose preference test, forced swimming test
(FST), open field test and elevated plus maze test and then detected the MAOA
content and MAOA gene transcriptional levels in the hippocampus with western blot
analysis and real-time quantitative PCR analysis. We then sought to reverse
depressive-like behavior of burned mice with an MAOA inhibitor. RESULTS: (1) Mice
showed depressive and anxiety like behaviors one week after they were burned; (2)
The content of MAOA in the hippocampus of burned mice was significantly higher
than that in control mice (P<0.05); (3) MAOA gene transcription in the
hippocampus of burned mice was significantly increased (MAOA mRNA was increased,
P<0.05); (4) treatment with a MAOA inhibitor (phenelzine) significantly increased
the sucrose preference rate and decreased FST immobility time in burned mice, and
also decreased elevated expression of MAOA in the hippocampus of burned mice.
CONCLUSION: Burned mice showed "delayed" depressive-like behavior combined with a
degree of anxiety; this phenomenon is likely associated with the increase in MAOA
expression in the hippocampus.
PMID- 28413108
TI - Moisturisers in scar management following burn: A survey report.
AB - : Scar management is a recognised key component of rehabilitation following burn.
Moisturising often combined with massage is commenced once healing tissue has
gained sufficient strength to tolerate surface friction, with the aim being to
hydrate the dry scar. The studies on various moisturisers and creams provide some
guidance on moisturiser selection, but many are inconclusive. OBJECTIVE: This
survey aimed to determine the current expert opinion regarding moisturiser
recommendations, including the basis for these recommendations, across the burns
community. METHODS: A brief web-based survey was distributed to burn therapists
via mailing lists of the Australian and New Zealand Burn Association (ANZBA), and
American Burn Association (ABA) 'Occupational and Physical Therapist Burn Special
Interest Group'. RESULTS: The fifty three respondents indicated that there were
29 different moisturisers commonly recommended in practice. Three main themes
were indicated as influencing recommendations for moisturiser: the perceived
effects on the scar/skin (48%); the general properties of the moisturiser (38%);
the ingredients (14%). Therapists reported that the principle stimuli determining
their recommendations were patient feedback and the choice of the previous burn
therapist in their service. Many were also guided by medical staff, pharmacists
and sales representatives. Only three respondents were able to provide citations
for published evidence supporting their recommendations. CONCLUSIONS: There is a
paucity of evidence currently to support optimal moisturiser choice. This survey
demonstrates that conflicting opinions are held on the ideal moisturiser brand,
properties and ingredients. The recommendations made are based on low level
evidence. Further research is required to inform clinicians which moisturiser to
recommend to their clients. An ideal moisturiser should be one that is conducive
to scar maturation, non- or minimally irritant, prevent skin drying, minimise
transepidermal water loss and have no negative effect on barrier function.
PMID- 28413109
TI - Development of an integrative algorithm for the treatment of various stages of
full-thickness burns of the first commissure of the hand.
AB - Burns of the first commissure of the hand can evolve into an adduction
contracture of the thumb. We decided to conduct a review of the existing
literature on the treatment of full-thickness burns of the first commissure in
order to develop a treatment algorithm that integrates the various currently
available procedures. A search of the existing literature was conducted, focusing
on the treatment of a burn of the first commissure in its chronic and acute
phases. A total of 29 relevant articles were selected; 24 focused exclusively on
the chronic contracture stage, while 3 focused exclusively on the acute burn
stage, and 2 articles studied both stages. A therapeutic algorithm for full
thickness burns of the first commissure of the hand was developed. With this
algorithm we sought to relate each degree and stage of the burn with a treatment.
PMID- 28413110
TI - Seawater immersion aggravates burn-associated lung injury and inflammatory and
oxidative-stress responses.
AB - With the increasing frequency of marine development activities and local wars at
sea, the incidence of scald burns in marine accidents or wars has been increasing
yearly. Various studies have indicated that immersion in seawater has a systemic
impact on some organs of animals or humans with burn. Thus, for burn/scald
injuries after immersion in seawater, it is desirable to study the effects and
mechanisms of action on important organs. In the present study, we aimed to
investigate the effect of immersion in seawater on lung injury, inflammatory and
oxidative-stress responses in scalded rats. The structural damage to lungs was
detected by hematoxylin and eosin staining and the results showed that seawater
immersion aggravated structural lung injury in scalded rats. The expression of
HMGB1 in lung tissues was detected by immunohistochemical analysis and the
results showed that seawater immersion increased HMGB1 expression in lung tissues
of scalded rats. Apoptosis in lung tissues was detected by terminal
deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) staining and
the results showed that seawater immersion increased apoptosis rate in lung
tissues of scalded rats. In addition, the expression levels of TNF-alpha, IL-6,
IL-8, SOD, and MDA in serum were analyzed by enzyme-linked immunosorbent assays
(ELISAs) and the results showed that seawater immersion induced secretion of
proinflammatory factors (TNF-alpha, IL-6, and IL-8), increased MDA protein level,
and suppressed SOD activity in the serum of scalded rats. Furthermore,
measurement of plasma volume and pH showed that seawater immersion decreased
plasma volume and pH value. Overall, the results indicated that all effects
induced by immersion in seawater in scalded rats are more pronounced than those
induced by freshwater. In conclusion, seawater immersion may aggravate lung
injury and enhance inflammatory and oxidative-stress responses after burn.
PMID- 28413111
TI - Comparison of clinical outcomes in diabetic and non-diabetic burns patients in a
national burns referral center in Southeast Asia: A 3-year retrospective review:
Methodological issues.
PMID- 28413112
TI - The effect of negative remodeling on fractional flow reserve after cardiac
transplantation.
AB - BACKGROUND: Negative remodeling is a common occurrence early after cardiac
transplantation. Its impact on the development of myocardial ischemia is not well
documented. The aim of this study is to investigate the impact of negative
remodeling on fractional flow reserve after cardiac transplantation. METHODS:
Thirty-four cardiac transplant recipients underwent intravascular ultrasound
(IVUS) and fractional flow reserve (FFR) assessment soon after transplantation
and one year later. Patients were divided into those with and without negative
remodeling based on IVUS, and the impact on FFR was assessed. In the 19 patients
with negative remodeling, there was no significant change in plaque volume
(119.3+/-82.0 to 131.3+/-91.2mm3, p=0.21), but vessel volume (775.6+/-212.0 to
621.9+/-144.1mm3, p<0.0001) and lumen volume (656.3+/-169.1 to 490.7+/-132.0mm3,
p<0.0001) decreased significantly and FFR likewise decreased significantly
(0.88+/-0.06 to 0.84+/-0.07, p=0.04). In the 15 patients without negative
remodeling, vessel volume did not change (711.7+/-217.6 to 745.7+/-198.5,
p=0.28), but there was a significant increase in plaque volume (126.8+/-88.3 to
194.4+/-92.7, p<0.001) and a resultant significant decrease in FFR (0.89+/-0.05
to 0.85+/-0.05, p=0.01). CONCLUSION: Negative remodeling itself, without any
change in plaque volume can cause a significant decrease in fractional flow
reserve after cardiac transplantation and appears to be another possible
mechanism for myocardial ischemia.
PMID- 28413113
TI - Association of low serum albumin concentration and adverse cardiovascular events
in stable coronary heart disease.
AB - OBJECTIVE: Coronary heart disease (CHD) is a leading cause of death in developed
countries. Exploration of indicators to identify high risk individuals who
develop adverse outcomes despite stable baseline condition is important. This
study is to evaluate the association between serum albumin concentration and
cardiovascular (CV) outcomes in individuals of stable CHD. METHODS: Seven-hundred
thirty-four participants from Biosignature study, a nationwide prospective cohort
study aimed to identity risk factors among patients with stable CHD, were
enrolled for analysis. They were divided into low serum albumin group (baseline
albumin concentration <3.5g/dL, n=98) and normal albumin group (baseline albumin
concentration >=3.5g/dL, n=636). The relations between baseline albumin and
adverse CV outcomes within 18months of follow-up were analyzed. RESULTS: Compared
baseline characteristics with normal albumin group, subjects in low albumin group
are older, having more diabetic patients, lower hemoglobin level, lower estimated
glomerular filtration rate, lower total cholesterol level, lower left ventricular
ejection fraction, and higher blood glucose. While there is no significant
difference of total CV events between two groups, low serum albumin concentration
is associated with an increased risk of all-cause mortality (10.2% vs. 0.5%,
p<0.001) and hard CV events (7.1% vs. 1.4%, p<0.001). The association remains
significant after adjustments for confounders (all-cause mortality, HR: 6.81, 95%
CI: 1.01-45.62; hard CV events, HR: 3.68, 95% CI: 1.03-13.19). CONCLUSIONS: Low
serum albumin concentration (<3.5g/dL) worsens prognosis of patients with stable
CHD.
PMID- 28413114
TI - Left atrial appendage thrombi relate to easily accessible clinical parameters in
patients undergoing atrial fibrillation transcatheter ablation: A multicenter
study.
AB - BACKGROUND: Transesophageal echocardiography (TEE) is routinely performed before
atrial fibrillation (AF) transcatheter ablation to exclude the presence of left
atrial (LA) or LA appendage (LAA) thrombi. The aim of the study is to evaluate if
easily accessible clinical parameters may relate to the presence of LA or LAA
thrombi to identify patients who could potentially avoid TEE. METHODS AND
RESULTS: Between January 2012 and September 2014, data from 1539 consecutive
patients undergoing TEE, as a work-up before AF transcatheter ablation, in six
large volume centers were collected. Baseline clinical features, CHA2DS2-VASc
score, transthoracic echocardiography and presence of thrombi at TEE were
recorded. Exclusion criteria were valvular, hypertrophic or dilated
cardiomyopathy, previous heart surgery or an ejection fraction <=35%. Mean age
was 59.6+/-10.4years, 1215 (78.9%) were males; 951 (62.9%) presented in sinus
rhythm (SR) on admission, 324 (21.1%) had undergone at least one previous
ablation and 900 (58.5%) had CHA2DS2-VASc score 0-1. Thrombi were encountered in
12 patients (0.8%). SR at TEE independently related to the absence of thrombi (OR
5.15, 95% CI 1.38-19.02, p=0.015); in addition to this, no patient with a CHA2DS2
VASc score 0-1 and SR on admission presented thrombi at TEE (specificity 100%,
p=0.011). CONCLUSION: In a selected population of patients referred for AF
ablation, LA/LAA thrombi prevalence is low. No patients in SR with CHA2DS2-VASc
score 0-1 presented LAA thrombi at TEE, identifying a significant subset of
patients who could potentially safely be spared from pre-procedural TEE.
PMID- 28413115
TI - Rate of contamination of hospital privacy curtains on a burns and plastic surgery
ward: a cross-sectional study.
AB - BACKGROUND: Surfaces in the patient environment may play a role in microbial
transmission if they become colonized by bacteria. Patient privacy curtains are
one such surface that may pose a high risk for transmission because they are high
contact surfaces, are infrequently cleaned, and healthcare workers are less
likely to wash their hands after contacting inanimate objects such as curtains.
AIM: To determine the amount and type of bacterial colonization of patient
privacy curtains at a regional burns/plastic surgery unit. METHODS: Privacy
curtain contamination on the burns/plastic surgery ward was determined for two
separate occasions six months apart: 23 curtains on August 2015 and 26 curtains
on January 2016. Dey-Engley neutralizing agar (DENA) replicate organism detection
and counting (RODAC) contact plates were used daily to sample curtains near the
edge hem where they are most frequently touched. Microbial contamination was
reported as cfu/cm2 and the presence of meticillin-resistant Staphylococcus
aureus (MRSA) was determined. Swabs were also taken of any open wounds and from
tracheostomy sites on the ward. FINDINGS: Curtain contamination in August 2015
was 0.7-4.7 cfu/cm2 with 22% testing positive for MRSA, whereas contamination on
January 2016 was 0.6-13.3 cfu/cm2 with 31% of curtains testing positive for MRSA.
CONCLUSION: Curtains on the burns/plastic surgery ward become colonized with
significant quantities of bacteria. Future studies will need to address the rate
of colonization and the clinical impact of this colonization to better inform
cleaning protocols.
PMID- 28413116
TI - Trunk Muscle EMG During Intermediate Pilates Mat Exercises in Beginner Healthy
and Chronic Low Back Pain Individuals.
AB - OBJECTIVE: The purpose of this study was to compare the electromyographic pattern
of core muscles during intermediate Pilates mat exercises between healthy people
and those with low back pain. METHODS: We evaluated healthy participants (n = 19;
mean +/- standard deviation [SD]: age 28 +/- 8 years, body mass 65 +/- 10 kg,
height 160.0 +/- 9.1 cm) and a low back pain group (n = 13; mean +/- SD: age 30
+/- 9 years, body mass 67 +/- 12 kg, height 170.0 +/- 6.6 cm). Electromyographic
analysis assessed the multifidus, external oblique, internal oblique, and rectus
abdominis muscles during classical Pilates exercises (single leg stretch, criss
cross, and dead bug). We calculated the root mean square normalized by maximum
voluntary contraction, and the time of peak activation was provided by a linear
envelope and normalized by the total movement cycle. RESULTS: The criss-cross
exercise presented the highest values of root mean square for trunk flexors
(rectus abdominis and oblique) compared with the other exercises, followed by the
single leg stretch and the dead bug, which had similar muscle activation. The
single leg stretch presented more activation of the rectus abdominis and oblique,
whereas the criss-cross and dead bug created more activation of the oblique
compared with the multifidus and rectus. CONCLUSIONS: The Pilates exercises
presented different muscle recruitment patterns, and allowed the activation of
the lumbopelvic stabilizing muscles even in the first session for healthy
individuals and those with chronic low back pain.
PMID- 28413117
TI - Structure-Specific Movement Patterns in Patients With Chronic Low Back
Dysfunction Using Lumbar Combined Movement Examination.
AB - OBJECTIVE: A test-retest cohort study was conducted to assess the use of a novel
computer-aided, combined movement examination (CME) to measure change in low back
movement after pain management intervention in 17 cases of lumbar spondylosis.
Additionally we desired to use a CME normal reference range (NRR) to compare and
contrast movement patterns identified from 3 specific structural pathologic
conditions: intervertebral disc, facet joint, and nerve root compression.
METHODS: Computer-aided CME was used before and after intervention, in a cohort
study design, to record lumbar range of movement along with pain, disability, and
health self-report questionnaires in 17 participants who received image-guided
facet, epidural, and/or rhizotomy intervention. In the majority of cases, CME was
reassessed after injection together with 2 serial self-reports after an average
of 2 and 14 weeks. A minimal clinically important difference of 30% was used to
interpret meaningful change in self-reports. A CME NRR (n = 159) was used for
comparison with the 17 cases. Post hoc observation included subgrouping cases
into 3 discrete pathologic conditions, intervertebral disc, facet dysfunction,
and nerve root compression, in order to report intergroup differences in CME
movement. RESULTS: Seven of the 17 participants stated that a "combined" movement
was their most painful CME direction. Self-report outcome data indicated that 4
participants experienced significant improvement in health survey, 5 improved by
>=30% on low back function, and 8 reported that low back pain was more bothersome
than stiffness, 6 of whom achieved the minimal clinically important difference
for self-reported pain. Subgrouping of cases into structure-specific groups
provided insight to different CME movement patterns. CONCLUSION: The use of CME
assists in identifying atypical lumbar movement relative to an age and sex NRR.
Data from this study, exemplified by representative case studies, provide
preliminary evidence for distinct intervertebral disc, facet joint, and nerve
root compression CME movement patterns in cases of chronic lumbar spondylosis.
PMID- 28413118
TI - Cadaveric and Ultrasonographic Validation of Needling Placement in the Cervical
Multifidus Muscle.
AB - OBJECTIVE: The aim of this study was to determine if a needle is able to reach
the cervical multifidus during the application of dry needling or acupuncture.
METHODS: Dry needling and ultrasound imaging of cervical multifidi was conducted
on 5 patients (age: 32 +/- 5 years) with mechanical neck pain and on 2 fresh
cadavers (age: 64 +/- 1 years). Dry needling was done using a needle of 40 mm in
length inserted perpendicular to the skin about 1 cm lateral to the spinous
process at C3-C4. The needle was advanced from a posterior to anterior direction
into the cervical multifidus with a slight inferior-medial angle (approximately
10 degrees ) to reach the vertebra lamina. For the cadaveric study, the
multifidus was isolated by carefully resecting the superficial posterior cervical
muscles: trapezius, splenius, and semispinalis. For the ultrasonographic study, a
convex transducer was placed transversely over C3-C4 after the insertion of the
needle into the muscle. RESULTS: The results of both the cadaveric and ultrasonic
studies found that the needle does pierce the cervical multifidus muscle during
insertion and that the tip of the needle rests properly against the vertebral
laminae, thereby guarding the sensitive underlying spinal structures from damage.
CONCLUSION: This anatomical and ultrasound imaging study supports that dry
needling of the cervical multifidus could be conducted clinically.
PMID- 28413119
TI - The two Dictyostelium discoideum autophagy 8 proteins have distinct autophagic
functions.
AB - Autophagy is a highly conserved cellular degradation pathway which is crucial for
various cellular processes. The autophagic process is subdivided in the
initiation, autophagosome maturation and lysosomal degradation phases and
involves more than forty core and accessory autophagy-related (ATG) proteins.
Autophagy 8 (ATG8, in mammals LC3) is a well-established marker of autophagy and
is linked to the autophagic membrane from initiation until fusion with the
lysosome. We generated single and double knock-out mutants of the two
Dictyostelium paralogues, ATG8a and ATG8b, as well as strains that expressed RFP
ATG8a and/or GFP-ATG8b, RFP-ATG8b, RFP-GFP-ATG8a or RFP-GFP-ATG8b in different
knock-out mutants. The ATG8b- mutant displayed only subtle phenotypic changes in
comparison to AX2 wild-type cells. In contrast, deletion of ATG8a resulted in a
complex phenotype with delayed development, reduced growth, phagocytosis and cell
viability, an increase in ubiquitinylated proteins and a concomitant decrease in
proteasomal activity. The phenotype of the ATG8a-/b- strain was, except for cell
viability, in all aforementioned aspects more severe, showing that both proteins
function in parallel during most analysed cellular processes. Immunofluorescence
analysis of knock-out strains expressing either RFP-GFP-ATG8a or RFP-GFP-ATG8b
suggests a crucial function for ATG8b in autophagosome-lysosome fusion.
Quantitative analysis of strains expressing RFP-ATG8a, RFP-ATG8b, or RFP-ATG8a
and GFP-ATG8b revealed that ATG8b generally localised to small and large
vesicles, whereas ATG8a preferentially co-localised with ATG8b on large vesicles,
indicating that ATG8b associated with nascent autophagosomes before ATG8a, which
is supported by previous results (Matthias et al., 2016). Deconvoluted confocal
fluorescence images showed that ATG8b localised around ATG8a and was presumably
mainly present on the outer membrane of the autophagosome while ATG8a appears to
be mainly associated with the inner membrane. In summary, our data show that
ATG8a and ATG8b have distinct functions and are involved in canonical as well as
non-canonical autophagy. The data further suggest that ATG8b predominantly acts
as adapter for the autophagy machinery at the outer and ATG8a as cargo receptor
at the inner membrane of the autophagosome.
PMID- 28413120
TI - Endosome to trans-Golgi network transport of Proprotein Convertase 7 is mediated
by a cluster of basic amino acids and palmitoylated cysteines.
AB - Proprotein Convertase 7 (PC7) is a Furin-like endoprotease that cleaves precursor
proteins at basic amino acids. PC7 is concentrated in the trans-Golgi network
(TGN) but it shuttles between the plasma membrane and the TGN depending on
sequences in the cytoplasmic tail. A short region containing a three amino acids
motif, P724-L725-C726, is essential and sufficient for internalization of PC7 but
not for TGN localization, which requires the additional presence of the
juxtamembrane region. In this study we have investigated the contribution of a
cluster of basic amino acids and two reversibly palmitoylated cysteine residues
to endocytic trafficking. Stable cell lines overexpressing chimeric proteins
(CD25 and CD46) containing the cytoplasmic domain of PC7 in which the basic
cluster alone or together with both palmitoylated cysteines are mutated showed
enhanced surface expression as demonstrated by immunofluorescence experiments and
surface biotinylation. The mutant proteins no longer recycled to the TGN in
antibody uptake experiments and accumulated in an endosomal compartment.
Recycling of wild type PC7 to the TGN is blocked by nocodazole, suggesting that
PC7 shuttles to the TGN via late endosomes, similar to Furin. Unlike furin,
however, PC7 was found to recycle to a region within the TGN, which is deficient
in sialyltransferase, as shown by resialylation experiments. In conclusion, a
novel motif, composed of a basic amino acid cluster and two palmitoylated
cysteines are essential for TGN localization and endocytic trafficking.
PMID- 28413121
TI - Characterisation of cell cycle arrest and terminal differentiation in a maximally
proliferative human epithelial tissue: Lessons from the human hair follicle
matrix.
AB - Human hair follicle (HF) growth and hair shaft formation require terminal
differentiation-associated cell cycle arrest of highly proliferative matrix
keratinocytes. However, the regulation of this complex event remains unknown.
CIP/KIP family member proteins (p21CIP1, p27KIP1 and p57KIP2) regulate cell cycle
progression/arrest, endoreplication, differentiation and apoptosis. Since they
have not yet been adequately characterized in the human HF, we asked whether and
where CIP/KIP proteins localise in the human hair matrix and pre-cortex in
relation to cell cycle activity and HF-specific epithelial cell differentiation
that is marked by keratin 85 (K85) protein expression. K85 expression coincided
with loss or reduction in cell cycle activity markers, including in situ DNA
synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1,
affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of
CIP/KIP proteins was found abundantly within the proliferative hair matrix,
concomitant with a role in cell cycle checkpoint control. p21CIP1, p27KIP1 and
cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas
p57KIP2 protein decreased but became nuclear. These data imply a supportive role
for CIP/KIP proteins in maintaining proliferative arrest, differentiation and
anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft
formation in anagen VI. Moreover, post-mitotic hair matrix regions contained
cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were
>2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance
cyclin E to control further rounds of DNA replication in a cell population that
has a propensity to become tetraploid. These data shed new light on the in situ
biography of human hair matrix keratinocytes on their path of active cell
cycling, arrest and terminal differentiation, and showcase the human HF as an
excellent, clinically relevant model system for cell cycle physiology research of
human epithelial cells within their natural tissue habitat.
PMID- 28413122
TI - Letter to the editor: Sepsis-associated in-hospital cardiac arrest: Epidemiology,
pathophysiology, and potential therapies.
PMID- 28413123
TI - Caution using the new "no pain no gain" approach.
PMID- 28413124
TI - Videolaryngoscopy for trauma patient intubation.
PMID- 28413125
TI - Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures
and late reduced diffusion.
AB - Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is
associated with various types of acquired brain injuries. Traumatic brain lesions
have been documented as the leading cause of PSH. However, detailed clinical
features of pediatric PSH caused by intrinsic brain lesions remain to be elusive.
We present a 3-year-old boy, who had been diagnosed as having cerebral palsy,
developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He
developed status epilepticus with fever on the third day of respiratory
infection. Whereas the seizure was terminated by systemic infusion of midazolam,
consciousness remained disturbed for the next 48h. Serial magnetic resonance
imaging studies revealed that acute encephalopathy with biphasic seizures and
late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic
hypothermia was immediately introduced, however, the brain lesion extended to the
whole subcortical white matters on day 8. The intermittent bilateral dilation of
pupils with increased blood pressure and tachycardia were observed until day 12.
Real-time monitoring of electroencephalograms ruled out the recurrent attacks of
seizures. The abnormal signs of autonomic nervous system gradually ceased and
never relapsed after recovery from the hypothermia. PSH or a transient condition
of dysautonomia may emerge and persist during the acute phase of AESD.
PMID- 28413126
TI - Consensus Statement of the European Urology Association and the European
Urogynaecological Association on the Use of Implanted Materials for Treating
Pelvic Organ Prolapse and Stress Urinary Incontinence.
AB - CONTEXT: Surgical nonautologous meshes have been used for several decades to
repair abdominal wall herniae. Implantable materials have been adopted for the
treatment of female and male stress urinary incontinence (SUI) and female pelvic
organ prolapse (POP). OBJECTIVE: A consensus review of existing data based on
published meta-analyses and reviews. EVIDENCE ACQUISITION: This document
summarises the deliberations of a consensus group meeting convened by the
European Association of Urology (EAU) and the European Urogynecological
Association, to explore the current evidence relating to the use of polypropylene
(PP) materials used for the treatment of SUI and POP, with reference to the 2016
EAU guidelines (European Association of Urology 2016), the European Commission's
SCENIHR report on the use of surgical meshes (SCENIHR 2015), other available high
quality evidence, guidelines, and national recommendations. EVIDENCE SYNTHESIS:
Current data suggest that the use of nonautologous durable materials in surgery
has well-established benefits but significant risks, which are specific to the
condition and location they are used for. Various graft-related complications
have been described-such as infection, chronic pain including dyspareunia,
exposure in the vagina, shrinkage, erosion into other organs of xenografts,
synthetic PP tapes (used in SUI), and meshes (used in POP)-which differ from the
complications seen with abdominal herniae. CONCLUSIONS: When considering surgery
for SUI, it is essential to evaluate the available options, which may include
synthetic midurethral slings (MUSs) using PP tapes, bulking agents,
colposuspension, and autologous sling surgery. The use of synthetic MUSs for
surgical treatment of SUI in both male and female patients has good efficacy and
acceptable morbidity. Synthetic mesh for POP should be used only in complex cases
with recurrent prolapse in the same compartment and restricted to those surgeons
with appropriate training who are working in multidisciplinary referral centres.
PATIENT SUMMARY: Synthetic slings can be safely used in the surgical treatment of
stress incontinence in both male and female patients. Patients need to be aware
of the alternative therapy and potential risks and complications of this therapy.
Synthetic mesh for treating prolapse should be used only in complex cases with
recurrent prolapse in specialist referral centres.
PMID- 28413127
TI - Evolution of Circulating Tumor DNA Profile from First-line to Subsequent Therapy
in Metastatic Renal Cell Carcinoma.
AB - BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails
mechanistically distinct agents across the first- and second-line setting.
Activity of these agents may be predicated on selective pressure that modulates
RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively
ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA
profile in a large cohort of mRCC patients, and to assess changes across patients
receiving first-line and later lines of therapy. DESIGN, SETTING, AND
PARTICIPANTS: We obtained the ctDNA profile in mRCC patients who received ctDNA
profiling as part of routine clinical care at progression using a 73-gene
Clinical Laboratory Improvement Amendments-certified ctDNA platform. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Genomic alterations (GAs) were pooled for
the entire cohort. A comparison of first- and postfirst-line was performed with
grouping based on conventional practice patterns (first-line regimens included
sunitinib, pazopanib, and bevacizumab, and postfirst-line regimens included
everolimus, axitinib, cabozantinib, and nivolumab). RESULTS AND LIMITATIONS:
ctDNA clinical results from a nationwide cohort of 220 consecutive patients with
mRCC were assessed (145 men, 75 women; median age: 63 yr, interquartile range: 57
70). GAs were detected in 78.6% of patients. The most frequent GAs in the overall
cohort included TP53 (35%), VHL (23%), EGFR (17%), NF1 (16%), and ARID1A (12%).
Thirty-eight and 64 patients were coded as receiving first-line and later line
agents, respectively. The highest disparity in GA frequencies in postfirst-line
versus first-line were in TP53 (49% vs 24%), VHL (29% vs 18%), NF1 (20% vs 3%),
EGFR (15% vs 8%), and PIK3CA (17% vs 8%) while ARID1A was equivalent (13% vs
11%). Restricting the analysis to later lines versus first-line vascular
endothelial growth factor inhibitors, these differences were even more prominent,
particularly for TP53 (64% vs 31%) and NF1 (29% vs 4%). CONCLUSIONS: In the
largest assessment of ctDNA-detected GAs prevalence in mRCC to date, the majority
of patients demonstrated clinically and biologically relevant GAs. Increasing p53
and mechanistic target of rapamycin pathway (eg, NF1, PIK3CA) alterations in
postfirst-line patients with first-line vascular endothelial growth factor
directed therapy may underlie mechanisms of resistance. Routine ctDNA assessment
during the clinical course of mRCC patients may have therapeutic implications.
PATIENT SUMMARY: Collection of circulating tumor DNA is feasible in patients with
metastatic renal cell carcinoma, and analysis of a large cohort demonstrates
significant changes in circulating tumor DNA profile across patients' clinical
course which may have therapeutic implications.
PMID- 28413128
TI - Immune Checkpoint Inhibition in Metastatic Urothelial Cancer.
AB - Immune checkpoint inhibitors are a new treatment option in metastatic urothelial
cancer on the basis of available phase 2 and 3 trials. Predictive biomarkers are
needed. These should go beyond PD-L1 expression, which is showing inconsistent
results across trials.
PMID- 28413129
TI - Return to Play After Osteochondral Autograft Transplantation of the Capitellum: A
Systematic Review.
AB - PURPOSE: To determine the rate of return to play and to identify lesion or
osteochondral graft characteristics that may influence the return to competitive
athletics after osteochondral autograft transplantation (OAT) for symptomatic
osteochondritis dissecans (OCD) lesions. METHODS: A systematic review was
conducted according to the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses guidelines. A duplicate search of PubMed, Embase, Scopus, Web of
Science, and CENTRAL databases was performed, beginning from the database
inception dates through July 2016, for all articles evaluating the return to play
after OAT for OCD lesions of the capitellum. A methodological quality assessment
was completed for all included studies. Patient demographics, osteochondral
lesion and graft characteristics, the number of patients, and timing of return to
competitive activity were collected and evaluated. Association between graft
size/number, the time to osseous healing, and return to sport was evaluated.
RESULTS: Seven articles met the inclusion criteria. All included studies were
case series of moderate quality with a mean Methodological Index for Non
Randomized Studies score of 12/16. Overall, 94% (119/126) of patients undergoing
OAT for OCD lesions of the capitellum successfully returned to competitive
sports. The mean reported time for unrestricted return to athletic competition
after OAT was 5.6 months (range, 3-14 months). CONCLUSIONS: Current best evidence
suggests that OAT is successful in treating advanced OCD lesions of the
capitellum and returning athletes to high-level competition. Evidence supporting
the association between the size and number of grafts used and the time to
osseous healing and return to sport is currently limited. Our assessment of the
time to return to athletic competition was limited because of variable surgical
technique, postoperative rehabilitation protocols, and outcome assessment. LEVEL
OF EVIDENCE: Level IV, systematic review of Level IV studies.
PMID- 28413130
TI - Arthroscopic Treatment of Labral Tears of the Hip in Adolescents: Patterns of
Clinical Presentation, Intra-articular Derangements, Radiological Associations
and Minimum 2-Year Outcomes.
AB - PURPOSE: To report on patterns of clinical presentation, intra-articular
derangements, radiological associations, and minimum 2-year outcomes after hip
arthroscopy (HA) in patients 18 years or younger. METHODS: This study was a
retrospective case series on patients 18 years or younger who had undergone HA
for labral tears that had failed nonoperative management from April 2008 to April
2013 with a minimum 2-year follow-up. Exclusion criteria were previous hip
conditions or surgery. The following were recorded: demographic, examination,
radiological and intraoperative findings, intraoperative procedures performed,
patient-reported outcomes (PROs), and patient satisfaction. The PROs reported
included the modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome
Score-Sport-Specific Subscale, Hip Outcome Score-Activities of Daily Living, and
Visual Analogue Score for pain. RESULTS: One hundred and two patients satisfied
the inclusion criteria, of whom 90 (88.2%, 77 females and 13 males) had minimum 2
year follow-up. Females had increased external rotation in flexion (58.9 degrees
vs 50.0 degrees , P = .041). Sixty-eight females had a Beighton's score of >4
compared to 6 males (P < .001). There was no distinct pattern within the group or
between genders for radiological markers of acetabular coverage, depth, or
version and femoral cam size. Mean femoral anteversion for females was 15.7
degrees and for males 11.3 degrees . Females had significantly smaller labral
tears (1.73 hours vs 2.34 hours on the acetabular clock face, P = .028). Females
were more likely to require a capsular plication and iliopsoas fractional
lengthening (88.3% vs 46.2%, and 77.9% vs 38.5%, respectively). There was a
significant improvement in all PRO measures in both males and females (P < .01),
but females had lower preoperative and postoperative scores. Mean preoperative
and postoperative PROs for males and females were as follows: modified Harris Hip
Score 71.0/94.3 and 63.4/88.8, Hip Outcome Score-Activities of Daily Living
78.1/93.4 and 64.0/91.8, Hip Outcome Score-Sport-Specific Subscale 51.7/91.0 and
45.7/78.6, Non-Arthritic Hip Score 78.1/94.5 and 63.1/89.2, and visual analog
score 4.77/1.85 and 6.29/2.21. The mean patient satisfaction score was 8.29 out
of 10. Five patients (5.56%) required a revision procedure. CONCLUSIONS: HA is
associated with improved outcomes and pain and high satisfaction scores at
minimum 2-year follow-up in adolescent population. The pattern of labral injury
is different in males and females and dictates the arthroscopic approach. Females
are likely to require a capsular plication and iliopsoas release to address soft
tissue laxity and impingement. LEVEL OF EVIDENCE: Level IV, therapeutic case
series.
PMID- 28413131
TI - Distress=stress? Disentangling the different components of emotional experience.
PMID- 28413132
TI - Development of an intradermal DNA vaccine delivery strategy to achieve single
dose immunity against respiratory syncytial virus.
AB - Respiratory syncytial virus (RSV) is a massive medical burden in infants,
children and the elderly worldwide, and an effective, safe RSV vaccine remains an
unmet need. Here we assess a novel vaccination strategy based on the intradermal
delivery of a SynCon(r) DNA-based vaccine encoding engineered RSV-F antigen using
a surface electroporation device (SEP) to target epidermal cells, in clinically
relevant experimental models. We demonstrate the ability of this strategy to
elicit robust immune responses. Importantly we demonstrate complete resistance to
pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A
challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine,
there was no enhanced lung inflammation upon virus challenge after DNA
vaccination. In summary the data presented outline the pre-clinical development
of a highly efficacious, tolerable and safe non-replicating vaccine delivery
strategy.
PMID- 28413133
TI - Vaccination with the polymorphic membrane protein A reduces Chlamydia muridarum
induced genital tract pathology.
AB - Chlamydia trachomatis serovars D-K are one of the most frequent causes of
sexually transmitted infections of the female genital tract, with possible
complications such as hydrosalpinx, pelvic inflammatory disease, extra-uterine
gravidity or infertility. We used the murine genital tract infection model with
C. muridarum for vaccination studies and found that more than 70% of the infected
mice suffered from uterus dilatations and/or hydrosalpinx. Systemic consequences
of the vaginal infection were apparent by splenomegaly ten to fifteen days post
infection. While cultivable microorganisms were detectable for the first 23days
post infection, the first lesions of the genital tract developed at day 15,
however, many lesions occurred later in the absence of cultivable bacteria.
Lesions were not accompanied by pro-inflammatory cytokines such as IFNgamma, TNF
and IL-6, since these cytokines were almost undetectable in the genital tract
43days post infection. To prevent genital tract lesions, we vaccinated mice with
the polymorphic membrane protein (Pmp) A in combination with CpG-ODN 1826 as
adjuvant. The vaccine lowered the chlamydial burden and the differences were
significant at day 10 post infection but not later. More importantly the vaccine
decreased the rate and severity of genital tract lesions. Interestingly, control
vaccination with the protein ovalbumin plus CpG-ODN 1826 enhanced significantly
the severity but not the rate of pathologic lesions, which was presumably caused
by the activation of innate immune responses by the adjuvant in the absence of a
C. muridarum-specific adaptive immune response. In summary, vaccination with
recombinant PmpA plus CpG-ODN 1826 significantly reduced C. muridarum-induced
tissue damage, however, CpG-ODN 1826 may aggravate C. muridarum-induced tissue
injuries in the absence of a protective antigen.
PMID- 28413134
TI - The in vitro MIMIC(r) platform reflects age-associated changes in immunological
responses after influenza vaccination.
AB - Increasing research and development costs coupled with growing concerns over
healthcare expenditures necessitate the generation of pre-clinical testing models
better able to predict the efficacy of vaccines, drugs and biologics. An ideal
system for evaluating vaccine immunogenicity will not only be reliable but also
physiologically relevant, able to be influenced by immunomodulatory
characteristics such as age or previous exposure to pathogens. We have previously
described a fully autologous human cell-based MIMIC(r) (Modular IMmune In vitro
Construct) platform which enables the evaluation of innate and adaptive immunity
in vitro, including naive and recall responses. Here, we establish the ability of
this module to display reduced antibody production and T cell activation upon in
vitro influenza vaccination of cells from elderly adults. In the MIMIC(r) system,
we observe a 2.7-4.2-fold reduction in strain-specific IgG production to seasonal
trivalent influenza vaccine (TIV) in the elderly when compared to adults, as well
as an age-dependent decline in the generation of functional antibodies. A
parallel decline in IgG production with increasing age was detected via short
term ex vivo stimulation of B cells after in vivo TIV vaccination in the same
cohort. Using MIMIC(r), we also detect a reduction in the number but not
proportion of TIV-specific multifunctional CD154+IFNgamma+IL-2+TNFalpha+ CD4+ T
cells in elderly adults. Inefficient induction of multifunctional helper T cells
with TIV stimulation in MIMIC(r) despite a normalized number of initial CD4+ T
cells suggests a possible mechanism for an impaired anti-TIV IgG response in
elderly adults. The ability of the MIMIC(r) system to recapitulate differential
age-associated responses in vitro provides a dynamic platform for the testing of
vaccine candidates and vaccine enhancement strategies in a fully human model
including the ability to interrogate specific populations, such as elderly
adults.
PMID- 28413135
TI - A systematic review of the diagnosis and treatment of patients with neurogenic
hyperactivity of the detrusor muscle.
AB - BACKGROUND: Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation
characterised by involuntary detrusor contractions during the filling phase that
are caused by an underlying neurological disease. The common and severe
complications that can result from NDH warrant the preparation of healthcare
protocols for the proper management of patients with NDH. OBJECTIVE: The aim of
this study is to standardise the criteria for the decision-making process in the
management of patients with diagnosed or suspected NDH, providing personalised
medical care. ACQUISITION OF EVIDENCE: We performed a systematic noncomprehensive
literature review on the aspects of the diagnosis and treatment of NDH. Based on
the review, recommendations were issued by nominal consensus of a group of
urology specialists. SYNTHESIS OF THE EVIDENCE: In general, the diagnosis of NDH
is arrived at by a proper review of the medical history, physical examination and
voiding diary before performing any diagnostic study. The main treatment
objectives are to protect the upper urinary tract, restore function of the lower
tract and improve these patients' continence and quality of life. The treatment
consists of several steps aimed at obtaining proper bladder storage that allows
for sufficiently spaced voidings. The follow-up should be personalised based on
each patient's needs. CONCLUSIONS: The identification and management of NDH is
important for positively redirecting the function of the lower urinary tract, in
terms of filling and voiding, thereby improving the patients' quality of life.
PMID- 28413136
TI - Opioid Use After Total Knee Arthroplasty: Trends and Risk Factors for Prolonged
Use.
AB - BACKGROUND: The United States is in the midst of an opioid epidemic. Little is
known about perioperative opioid use for total knee arthroplasty (TKA). The
purpose of this study was to identify rates of preoperative opioid use, evaluate
postoperative trends and identify risk factors for prolonged use after TKA.
METHODS: Patients who underwent primary TKA from 2007-2014 were identified within
the Humana database. Postoperative opioid use was measured by monthly
prescription refill rates. A preoperative opioid user (OU) was defined by history
of opioid prescription within 3 months prior to TKA and a non-opioid user (NOU)
was defined by no history of prior opioid use. Rates of opioid use were trended
monthly for one year postoperatively for all cohorts. RESULTS: 73,959 TKA
patients were analyzed and 23,532 patients (31.2%) were OU. OU increased from
30.1% in 2007 to 39.3% in 2014 (P < .001). Preoperative opioid use was the
strongest predictor for prolonged opioid use following TKA, with OU filling
significantly more opioid prescriptions than NOU at every time point analyzed.
Younger age, female sex and other intrinsic factors were found to significantly
increase the rate of opioid refilling following TKA throughout the postoperative
year. CONCLUSION: Approximately one-third of TKA patients use opioids within 3
months prior to surgery and this percentage has increased over 9% during the
years included in this study. Preoperative opioid use was most predictive of
increased refills of opioids following TKA. However, other intrinsic patient
characteristics were also predictive of prolonged opioid use.
PMID- 28413137
TI - Response to Letter to the Editor on "Efficacy in Deep Vein Thrombosis Prevention
With Extended Mechanical Compression Device Therapy and Prophylactic Aspirin
Following Total Knee Arthroplasty: A Randomized Control Trial".
PMID- 28413138
TI - Letter to the Editor on "Efficacy in Deep Vein Thrombosis Prevention With
Extended Mechanical Compression Device Therapy and Prophylactic Aspirin Following
Total Knee Arthroplasty: A Randomized Control Trial".
PMID- 28413139
TI - Evaluation of Extensor Mechanism in Revision Knee Arthroplasty.
AB - BACKGROUND: The success of revision total knee arthroplasty depends on adequate
exposure that does not produce complications. The purpose of this study was to
compare the results of revision total knee arthroplasty between V-Y
quadricepsplasty (QP) and quadriceps snip (QS) approaches. METHODS: In the study,
92 knees with follow-up of 12-108 months which were operated by using QP (55) and
QS (37) were evaluated retrospectively. Measurements were taken by using
universal transparent goniometer, also varus valgus deformities, knee flexion
angles, instability, Hospital for Special Surgery and Lower Extremity Functional
Scale scores, functional condition of the knee and activity levels of the
patients were evaluated cross-sectionally. RESULTS: Statistically significant
difference was not found regarding extensor restriction, varus or valgus
deformities, knee flexion angles, flexor and extensor muscular strength, Hospital
for Special Surgery and Lower Extremity Functional Scale score (P > .05).
CONCLUSION: QP is a preferable method which allows a wider arthrotomy for stiff
knees and revision knee surgery, and provides larger access to the joint.
Choosing this incision does not bring disadvantage in terms of extensor
mechanism.
PMID- 28413140
TI - Is Day of Surgery Associated With Adverse Clinical and Economic Outcomes
Following Primary Total Knee Arthroplasty?
AB - BACKGROUND: As orthopedics transition to value-based purchasing, hospitals and
providers are incentivized to identify inefficiencies of care delivery. In our
experience, weekends are characterized by decreased staffing of ancillary
services to coordinate patient discharges, which can lead to prolonged hospital
stays for many of our primary total knee arthroplasty (TKA) admissions. METHODS:
We identified 115,053 patients who underwent primary TKA on a weekday between
2009 and 2013 in New York State. We used mixed effects regression models to
compare length of stay (LOS), 90-day readmission, and cost according to the day
of TKA. RESULTS: Mean LOS was significantly higher for surgeries performed on
Wednesday (P < .001), Thursday (P < .001), and Friday (P < .001). There was no
significant difference in 90-day readmission risk according to day of surgery.
Mean cost was significantly higher for surgeries performed on Wednesday (P <
.001), Thursday (P < .001), and Friday (P < .001). When LOS was held constant
across every day of the week, the mean cost of TKA decreased by $247 for
Wednesday, $627 for Thursday, and $394 for Friday. CONCLUSION: Primary TKA
performed later in the week is associated with an increased LOS and increased
costs of admission, but a similar risk of 90-day readmission. Preferential
scheduling of primary TKA cases early in the week, as well as the development of
standardized clinical care pathways with appropriate weekend staffing of social
work and rehabilitation services, could help to decrease the daily variation in
LOS and increase the value of TKA episodes.
PMID- 28413141
TI - Response to Letter to the Editor on "Patient Reported Kneeling Ability in Fixed
and Mobile Bearing Knee Arthroplasty".
PMID- 28413142
TI - Outcomes of Modular Dual Mobility Acetabular Components in Revision Total Hip
Arthroplasty.
AB - BACKGROUND: There is a high rate of dislocation after revision total hip
arthroplasty. This study evaluated the outcomes of 1 modular dual mobility
component in revision total hip arthroplasty in patients at high risk of
dislocation. METHODS: We reviewed 64 revisions performed in 27 (42%) patients for
recurrent dislocation, 16 (25%) for adverse local tissue reaction, 11 (17%) for
reimplantation infection, and 10 (16%) for aseptic loosening, malposition, or
fracture. Complications, reoperations, and survivorship were evaluated. RESULTS:
Three-year survival was 98% with failure defined as aseptic loosening and 91%
with failure as cup removal for any reason. With mean follow-up time of 38
months, there were 14 complications, including 2 dislocations treated with closed
reduction, 9 infections, and 12 reoperations. All complications occurred in
patients revised for instability, adverse local tissue reaction, or infection.
CONCLUSION: The early results of this component are promising, with good overall
survival and low rate of dislocation.
PMID- 28413143
TI - Arab American Health in a Racially Charged U.S.
PMID- 28413144
TI - [A health system ill at ease with itself].
PMID- 28413145
TI - Body piercing and tattooing among French patients with bleeding disorders.
PMID- 28413146
TI - [Multiple ground-glass opacities nodules].
AB - INTRODUCTION: Ground-glass opacities nodules are frequently detected with the
advances of radiological imaging. These can be preinvasive lesions such as
atypical adenomatous hyperplasia but also invasive lesions. It leads to question
in patients with lung cancer about treatment strategy and follow up. CASE REPORT:
We report the case of a 72 years-old woman followed for a lung adenocarcinoma
with an EGFR mutation of the right upper lobe stage IIb. The CT scan shows
multiple pure ground-glass opacities in the same lobe of the primitive tumor but
also in the other lobe. On the piece of lobectomy, histopathology of two ground
glass opacities showed atypical adenomatous hyperplasia. CONCLUSION: Ground-glass
opacities nodules could be found in patients with an operable lung cancer. These
can be multiple and match with atypical adenomatous hyperplasia but also
carcinomas lesions. The radiological surveillance is still the standard. The
strategy for surgical resection has to be defined especially in case of multiple
lesions which can require repeated surgical resection.
PMID- 28413147
TI - Branchial cleft cyst: An unusual site for the cervical metastasis of
nasopharyngeal carcinoma.
AB - OBJECTIVE: Cancers found in the resected branchial cleft cyst are rare clinically
but usually impose substantive diagnostic and treatment challenges for
clinicians. METHODS: A 31-year-old man presented with a lateral neck mass that
was suspected to be an inflammatory branchial cleft cyst. After excision, the
pathologic specimen revealed a benign cystic appearance with a focus of
undifferentiated carcinoma. Serologic tests for Epstein-Barr virus were negative.
A positron emission tomography scan and upper aerodigestive tract endoscopies
were negative for any other suspicious lesion. RESULTS: The patient underwent
random biopsies of the nasopharynx, tongue base, and hypopharynx and bil
tonsillectomy. Pathologic examination of the nasopharyngeal biopsies showed the
presence of undifferentiated carcinoma. The cancerous part of the branchial cleft
cyst and this nasopharyngeal specimen were positive for the latent membrane
protein-1 and EBV-encoded RNAs of Epstein-Barr virus (EBV) and confirmed our
diagnosis. CONCLUSION: This is the first report of a NPC metastasizing to a
branchial cleft cyst. Molecular diagnostic techniques facilitate the definite
diagnosis that enabled us to refine treatment plans and offered the patient a
favorable outcome.
PMID- 28413148
TI - Incorporating Site-less Clinical Trials Into Drug Development: A Framework for
Action.
AB - PURPOSE: Options for leveraging available telemedicine technologies, ranging from
simple webcams and telephones to smartphone apps and medical-grade wearable
sensors, are evolving faster than the culture of clinical research. Until
recently, most clinical trials relied on paper-based processes and technology.
This cost- and labor-intensive system, while slowly changing, remains an obstacle
to new drug development. Alternatives that use existing tools and processes for
collecting real-world data in home settings warrant closer examination. METHODS:
The site-less clinical research organization (CRO) model, whereby pharmacists or
other health care professionals provide useful and timely counseling for protocol
compliance by regular phone and videoconferencing sessions, is a flexible
approach to managing clinical trial participants directly from their homes. An
expert panel, including clinical specialists in metabolic or neurodegenerative
diseases, health information technology and CRO innovators, and the
pharmaceutical industry, met in Dallas, Texas, December 2016, to discuss
advancing avenues for site-less CRO and other remote clinical trial practices,
taking into account investigator, sponsor, and regulatory perspectives. FINDINGS:
Real-time "site-less" management of clinical trials can augment traditional
research and development methods by providing data from a broader, more diverse
group of patients in real-world practice settings. This methodology also helps to
proactively identify safety profile and operational issues. Current use of site
less CRO practices constitutes an important bridge to alternative trial models,
including "large simple trials" that strive to answer one or two questions using
data derived from representative patient populations treated in typical clinical
settings. IMPLICATIONS: Site-less CROs offer a working example of how remote
technologies and in-home monitoring methods can address shortcomings of
conventional drug development. This model maximizes time and cost, as well as
potentially earlier identification of adverse events. Coordinated communication
among investigators, sponsors, regulators, and patients will be needed to develop
standardized strategies for incorporating site-less CROs into current and future
study design.
PMID- 28413150
TI - Nerve Conduits-Necessity or Nicety?
PMID- 28413149
TI - Association of Temporomandibular Joint Pain According to Magnetic Resonance
Imaging Findings in Temporomandibular Disorder Patients.
AB - PURPOSE: This study investigated the associations between magnetic resonance
imaging (MRI) findings and pain in the temporomandibular joint (TMJ). MATERIALS
AND METHODS: The study included 646 TMJs of 323 consecutive patients with
temporomandibular disorders; of these, 222 (34.4%) had TMJ pain whereas 424
(65.6%) had no TMJ pain. MRIs were used to evaluate disc position,
osteoarthritis, joint fluid, and bone marrow edema. Internal derangement was
classified as normal, anterior disc displacement with reduction, and anterior
disc displacement without reduction (ADDWOR); condylar morphology was classified
as normal, moderate bony change, and severe bony change. The odds ratio (OR) for
each MRI variable for nonpainful versus painful TMJs was computed using logistic
regression analysis. RESULTS: Compared with joints with normal disc position, the
OR of those with ADDWOR was 2.74 (P < .001) for TMJ pain. Similarly, compared
with joints with normal condylar morphology, the OR of those with severe bony
change was 4.62 (P = .02) for TMJ pain. In addition, the risk of TMJ pain
increased by 2.37 in joints with joint fluid (P < .001) and by 2.34 in joints
with bone marrow edema (P = .006). The risk of TMJ pain increased significantly
with ADDWOR in combination with severe bony change, joint fluid, and bone marrow
edema. CONCLUSIONS: These results suggest an association between TMJ pain and
ADDWOR, severe bony change, joint fluid, and bone marrow edema. Thus, combining
various MRI variables may improve the diagnostic accuracy of TMJ pain.
PMID- 28413151
TI - Public and Patient Knowledge About Dental Implants.
AB - PURPOSE: The more informed a patient is about a given procedure, the better the
ultimate outcome. This study was designed to compare general public awareness and
knowledge regarding oral implant treatment with those of patients presenting for
such treatment and to determine the sources from which they may have obtained
such information, as well as the accuracy of the information. PATIENTS AND
METHODS: In this cross-sectional study, 2 groups of patients were asked to
complete a questionnaire containing implant knowledge questions and questions
regarding any sources they may have used to obtain information about dental
implants. Group I consisted of patients presenting for treatment of a dental
emergency (general population group), and group II consisted of patients
presenting for an implant consultation. The chi2 test was used to determine
whether there were differences in knowledge and information sources between the 2
groups. RESULTS: A total of 126 adult patients (76 dental emergency patients and
50 implant consultation patients) participated in the study. The general
population group was less informed about dental implants, especially information
relating to implant material and longevity, and received information from less
reliable sources than patients presenting for implant screening (friends or
relatives vs primary dentist). Both groups reported cost of the procedure as a
primary barrier to receiving implants (89% and 90%). CONCLUSIONS: There is still
a need for continued education of the general public regarding dental implants.
PMID- 28413152
TI - Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor
Prognosis in Patients With Tongue Squamous Cell Carcinoma.
AB - PURPOSE: The aim of this study was to detect the relationship between phosphatase
and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and
correlate PTEN expression with important clinical parameters of patients with
tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: In this
retrospective case series, all TSCC patients treated at Tianjin Medical
University Cancer Institute and Hospital between March 2005 and October 2011 were
retrospectively reviewed. Demographic information and clinical data (histologic
type, clinical stage, tumor differentiation, and so on) were collected. The miR
24 level was detected by quantitative reverse transcription-polymerase chain
reaction. The PTEN level was analyzed by immunohistochemistry and quantitative
reverse transcription-polymerase chain reaction. Data analyses were performed by
Spearman correlation analysis, Pearson chi2 test, and paired t test. Kaplan-Meier
curves, log-rank analyses, and a Cox proportional hazards model were used to
evaluate the prognostic value of PTEN. RESULTS: A total of 90 patients (aged 59.4
+/- 9.5 years, 53 men and 37 women) were identified. Loss of PTEN expression was
detected in 28 of 90 tumors (31.1%). The PTEN messenger RNA level was negatively
correlated with the miR-24 level (r = -0.569, P < .01). PTEN expression also was
negatively correlated with the miR-24 level (r = -0.621, P < .01). Furthermore,
PTEN expression was significantly lower in cancer tissues than in adjacent normal
tissues, and its expression was negatively correlated with clinical stage (P <
.01) and positively correlated with differentiation (P < .05) in TSCC patients.
In addition, the Kaplan-Meier curve indicated that loss of PTEN expression
resulted in poor survival of TSCC patients (P < .01). Multivariate analysis
indicated that PTEN expression level and clinical stage may be independent
prognostic factors for TSCC patients. CONCLUSIONS: This study suggested that PTEN
expression was negatively correlated with the miR-24 level in TSCC. The loss of
PTEN expression may serve as a predictor of unfavorable prognosis for TSCC
patients.
PMID- 28413153
TI - Contribution by CGG Aitken to discussion of Meuwly et al. (2016).
PMID- 28413154
TI - Is Withaferin A, a magic bullet for metabolic syndrome?
PMID- 28413155
TI - Effects of natural environment on reproductive histo-morphometric dynamics of
female dromedary camel.
AB - Camel shows a seasonal breeding pattern with enhanced reproductive activity
during the period of low climatic temperature, high rainfall and better food
conditions. Therefore, the study was conducted to explore the underlying seasonal
effects on histological dimensions of reproductive tract in adult female one
humped camel (Camelus dromedarius) kept in the natural environment of Pakistan. A
total 25 reproductive tracts were collected during spring, summer, autumn and
winter seasons and were analysed for histo-morphometric parameters during
different environmental conditions. A significant increase in number (p<0.05) and
size (p<0.05) of surface with secondary and tertiary ovarian follicles was
observed in winter season. The epithelial height (p<0.05) and luminal diameter
(p<0.05) of infundibulum, ampulla and isthmus of uterine tubes were also
significantly increased during winter season. Moreover, significantly increased
length (p<0.05) and circumference (p<0.05) of uterine cornua, increased number
(p<0.001) and diameter (p<0.001) of endometrial glands with enlarged surface and
glandular epithelia (p<0.001) were found in winter compared to summer season.
Therefore, we concluded that quiescent ovarian follicular and uterine glandular
activities are the main reason of camel low breeding during summer season.
PMID- 28413156
TI - Exposure of the Amino Terminus of Tau Is a Pathological Event in Multiple
Tauopathies.
AB - Pathological changes to the tau protein, including conformational changes and
aggregation, are major hallmarks of a group of neurodegenerative disorders known
as tauopathies. Among the conformational changes are alterations involving the
extreme amino terminus of the protein, known as the phosphatase-activating domain
(PAD). Aberrant PAD exposure induces a signaling cascade that leads to disruption
of axonal transport, a critical function for neuronal survival. Conformational
display of PAD is an early marker of pathological tau in Alzheimer disease (AD),
but its role in other tauopathies has yet to be firmly established. We used a
relatively novel N-terminal, conformation-sensitive antibody, TNT2, to determine
whether misfolding in the amino terminus (ie, PAD exposure) occurs in non-AD
tauopathies. We found that TNT2 specifically labeled pathological tau in post
mortem human brain tissue from Pick disease, progressive supranuclear palsy,
corticobasal degeneration, and chronic traumatic encephalopathy, but did not
label nonpathological, parenchymal tau. Tau13, another N-terminal antibody, was
not sensitive to pathological N-terminal conformations. Tau13 did not readily
distinguish between normal (ie, parenchymal tau) and pathological tau species and
showed a range of effectiveness at identifying tau pathologies in the non-AD
tauopathies. These findings demonstrate that the conformational display of the
PAD in tau represents a common pathological event in many tauopathies.
PMID- 28413157
TI - Long-term stabilisation of myeloma with curcumin.
AB - Myeloma is a haematological malignancy which typically follows a relapsing
remitting course. While treatment can control the myeloma and improve quality of
life for given periods of time, remissions generally become progressively shorter
with subsequent relapses, and patients ultimately enter a final refractory phase.
To help control symptoms and enhance quality of life, some patients use
complementary therapies as an adjunct to their conventional therapy. Here, we
describe a myeloma patient who started a daily dietary supplement of curcumin
when approaching her third relapse. In the absence of further antimyeloma
treatment, the patient plateaued and has remained stable for the last 5 years
with good quality of life.
PMID- 28413158
TI - Inferring Demographic History Using Two-Locus Statistics.
AB - Population demographic history may be learned from contemporary genetic variation
data. Methods based on aggregating the statistics of many single loci into an
allele frequency spectrum (AFS) have proven powerful, but such methods ignore
potentially informative patterns of linkage disequilibrium (LD) between
neighboring loci. To leverage such patterns, we developed a composite-likelihood
framework for inferring demographic history from aggregated statistics of pairs
of loci. Using this framework, we show that two-locus statistics are more
sensitive to demographic history than single-locus statistics such as the AFS. In
particular, two-locus statistics escape the notorious confounding of depth and
duration of a bottleneck, and they provide a means to estimate effective
population size based on the recombination rather than mutation rate. We applied
our approach to a Zambian population of Drosophila melanogaster Notably, using
both single- and two-locus statistics, we inferred a substantially lower
ancestral effective population size than previous works and did not infer a
bottleneck history. Together, our results demonstrate the broad potential for two
locus statistics to enable powerful population genetic inference.
PMID- 28413159
TI - The Hippo Pathway Maintains the Equatorial Division Plane in the Ciliate
Tetrahymena.
AB - The mechanisms that govern pattern formation within the cell are poorly
understood. Ciliates carry on their surface an elaborate pattern of cortical
organelles that are arranged along the anteroposterior and circumferential axes
by largely unknown mechanisms. Ciliates divide by tandem duplication: the cortex
of the predivision cell is remodeled into two similarly sized and complete
daughters. In the conditional cdaI-1 mutant of Tetrahymena thermophila, the
division plane migrates from its initially correct equatorial position toward the
cell's anterior, resulting in unequal cell division, and defects in nuclear
divisions and cytokinesis. We used comparative whole genome sequencing to
identify the cause of cdaI-1 as a mutation in a Hippo/Mst kinase. CdaI is a
cortical protein with a cell cycle-dependent, highly polarized localization.
Early in cell division, CdaI marks the anterior half of the cell, and later
concentrates at the posterior end of the emerging anterior daughter. Despite the
strong association of CdaI with the new posterior cell end, the cdaI-1 mutation
does not affect the patterning of the new posterior cortical organelles. We
conclude that, in Tetrahymena, the Hippo pathway maintains an equatorial position
of the fission zone, and, by this activity, specifies the relative dimensions of
the anterior and posterior daughter cell.
PMID- 28413160
TI - Interaction Between Familial Transmission and a Constitutively Active Immune
System Shapes Gut Microbiota in Drosophila melanogaster.
AB - Resident gut bacteria are constantly influencing the immune system, yet the role
of the immune system in shaping microbiota composition during an organism's life
span has remained unclear. Experiments in mice have been inconclusive due to
differences in husbandry schemes that led to conflicting results. We used
Drosophila as a genetically tractable system with a simpler gut bacterial
population structure streamlined genetic backgrounds and established cross
schemes to address this issue. We found that, depending on their genetic
background, young flies had microbiota of different diversities that converged
with age to the same Acetobacteraceae-dominated pattern in healthy flies. This
pattern was accelerated in immune-compromised flies with higher bacterial load
and gut cell death. Nevertheless, immune-compromised flies resembled their
genetic background, indicating that familial transmission was the main force
regulating gut microbiota. In contrast, flies with a constitutively active immune
system had microbiota readily distinguishable from their genetic background with
the introduction and establishment of previously undetectable bacterial families.
This indicated the influence of immunity over familial transmission. Moreover,
hyperactive immunity and increased enterocyte death resulted in the highest
bacterial load observed starting from early adulthood. Cohousing experiments
showed that the microenvironment also played an important role in the structure
of the microbiota where flies with constitutive immunity defined the gut
microbiota of their cohabitants. Our data show that, in Drosophila,
constitutively active immunity shapes the structure and density of gut
microbiota.
PMID- 28413161
TI - Rapid and Recent Evolution of LTR Retrotransposons Drives Rice Genome Evolution
During the Speciation of AA-Genome Oryza Species.
AB - The dynamics of long terminal repeat (LTR) retrotransposons and their
contribution to genome evolution during plant speciation have remained largely
unanswered. Here, we perform a genome-wide comparison of all eight Oryza AA
genome species, and identify 3911 intact LTR retrotransposons classified into 790
families. The top 44 most abundant LTR retrotransposon families show patterns of
rapid and distinct diversification since the species split over the last ~4.8 MY
(million years). Phylogenetic and read depth analyses of 11 representative
retrotransposon families further provide a comprehensive evolutionary landscape
of these changes. Compared with Ty1-copia, independent bursts of Ty3-gypsy
retrotransposon expansions have occurred with the three largest showing
signatures of lineage-specific evolution. The estimated insertion times of 2213
complete retrotransposons from the top 23 most abundant families reveal divergent
life histories marked by speedy accumulation, decline, and extinction that
differed radically between species. We hypothesize that this rapid evolution of
LTR retrotransposons not only divergently shaped the architecture of rice genomes
but also contributed to the process of speciation and diversification of rice.
PMID- 28413163
TI - ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride
clearance.
AB - Angiopoietin-like (ANGPTL)3 and ANGPTL8 are secreted proteins and inhibitors of
LPL-mediated plasma triglyceride (TG) clearance. It is unclear how these two
ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity
and increases serum TG independent of ANGPTL8. These effects are reversed with an
ANGPTL3 blocking antibody. Here, we show that ANGPTL8, although it possesses a
functional inhibitory motif, is inactive by itself and requires ANGPTL3
expression to inhibit LPL and increase plasma TG. Using a mutated form of ANGPTL3
that lacks LPL inhibitory activity, we demonstrate that ANGPTL3 activity is not
required for its ability to activate ANGPTL8. Moreover, coexpression of ANGPTL3
and ANGPTL8 leads to a far more efficacious increase in TG in mice than ANGPTL3
alone, suggesting the major inhibitory activity of this complex derives from
ANGPTL8. An antibody to the C terminus of ANGPTL8 reversed LPL inhibition by
ANGPTL8 in the presence of ANGPTL3. The antibody did not disrupt the
ANGPTL8:ANGPTL3 complex, but came in close proximity to the LPL inhibitory motif
in the N terminus of ANGPTL8. Collectively, these data show that ANGPTL8 has a
functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG
levels in mice in the presence of ANGPTL3.
PMID- 28413162
TI - Whole-Genome Sequence of the Metastatic PC3 and LNCaP Human Prostate Cancer Cell
Lines.
AB - The bone metastasis-derived PC3 and the lymph node metastasis-derived LNCaP
prostate cancer cell lines are widely studied, having been described in thousands
of publications over the last four decades. Here, we report short-read whole
genome sequencing (WGS) and de novo assembly of PC3 (ATCC CRL-1435) and LNCaP
(clone FGC; ATCC CRL-1740) at ~70 * coverage. A known homozygous mutation in TP53
and homozygous loss of PTEN were robustly identified in the PC3 cell line,
whereas the LNCaP cell line exhibited a larger number of putative inactivating
somatic point and indel mutations (and in particular a loss of stop codon
events). This study also provides preliminary evidence that loss of one or both
copies of the tumor suppressor Capicua (CIC) contributes to primary tumor relapse
and metastatic progression, potentially offering a treatment target for
castration-resistant prostate cancer (CRPC). Our work provides a resource for
genetic, genomic, and biological studies employing two commonly-used prostate
cancer cell lines.
PMID- 28413164
TI - Resistance Economy and New Population Policy in Iran.
AB - .
PMID- 28413165
TI - Applying Multi-Theory Model (MTM) of Health Behavior Change to Predict Water
Consumption Instead of Sugar-Sweetened Beverages.
AB - BACKGROUND: A substantial proportion of college students to not drink enough
water and consume sugar-sweetened beverages (SSBs). Consumption of SSBs is
associated with weight gain, obesity, type 2 diabetes mellitus, dental carries,
and increased risk for cardiovascular disease. Hence, the purpose of this study
was to use the multi-theory model (MTM) in predicting initiation and sustenance
of plain water consumption instead of sugar-sweetened beverages among college
students. STUDY DESIGN: A cross-sectional study. METHODS: In this cross-sectional
study, a 37-item valid and reliable MTM-based survey was administered to college
students in 2016 via Qualtrics at a large public university in the Southeastern
United States. Overall, 410 students responded to the survey; of those, 174 were
eligible for the study and completed it. RESULTS: Stepwise multiple regression
analysis revealed that 61.8% of the variance in the initiation of drinking plain
water instead of SSBs was explained by behavioral confidence (P<0.001) and
changes in the physical environment (P<0.001). Further, 58.3% of the variance in
the sustenance of drinking plain water instead of SSBs was explained by emotional
transformation (P<0.001) and practice for change (P=0.001). CONCLUSIONS: Multi
theory model of health behavior change is a robust theory for predicting plain
water consumption instead of SSBs in college students. Interventions should be
developed based on this theory for this target population.
PMID- 28413166
TI - Health Literacy Scale and Causal Model of Childhood Overweight.
AB - BACKGROUND: WHO focuses on developing health literacy (HL) referring to cognitive
and social skills. Our objectives were to develop a scale for evaluating the HL
level of Thai childhood overweight, and develop a path model of health behavior
(HB) for preventing obesity. STUDY DESIGN: A cross-sectional study. METHODS: This
research used a mixed method. Overall, 2,000 school students were aged 9 to 14 yr
collected by stratified random sampling from all parts of Thailand in 2014. Data
were analyzed by CFA, LISREL. RESULTS: Reliability of HL and HB scale ranged 0.62
to 0.82 and factor loading ranged 0.33 to 0.80, the subjects had low level of HL
(60.0%) and fair level of HB (58.4%), and the path model of HB, could be
influenced by HL from three paths. Path 1 started from the health knowledge and
understanding that directly influenced the eating behavior (effect sized - beta
was 0.13, P<0.05. Path 2 the health knowledge and understanding that influenced
managing their health conditions, media literacy, and making appropriate health
related decision beta=0.07, 0.98, and 0.05, respectively. Path 3 the accessing
the information and services that influenced communicating for added skills,
media literacy, and making appropriate health-related decision beta=0.63, 0.93,
0.98, and 0.05. Finally, basic level of HL measured from health knowledge and
understanding and accessing the information and services that influenced HB
through interactive, and critical level beta= 0.76, 0.97, and 0.55, respectively.
CONCLUSIONS: HL Scale for Thai childhood overweight should be implemented as a
screening tool developing HL by the public policy for health promotion.
PMID- 28413167
TI - Impact of a New Law to Reduce the Legal Blood Alcohol Concentration Limit - A
Poisson Regression Analysis and Descriptive Approach.
AB - BACKGROUND: In Chile, a new law introduced in March 2012 lowered the blood
alcohol concentration (BAC) limit for impaired drivers from 0.1% to 0.08% and the
BAC limit for driving under the influence of alcohol from 0.05% to 0.03%, but its
effectiveness remains uncertain. The goal of this investigation was to evaluate
the effects of this enactment on road traffic injuries and fatalities in Chile.
STUDY DESIGN: A retrospective cohort study. METHODS: Data were analyzed using a
descriptive and a Generalized Linear Models approach, type of Poisson regression,
to analyze deaths and injuries in a series of additive Log-Linear Models
accounting for the effects of law implementation, month influence, a linear time
trend and population exposure. A review of national databases in Chile was
conducted from 2003 to 2014 to evaluate the monthly rates of traffic fatalities
and injuries associated to alcohol and in total. RESULTS: It was observed a
decrease by 28.1 percent in the monthly rate of traffic fatalities related to
alcohol as compared to before the law (P<0.001). Adding a linear time trend as a
predictor, the decrease was by 20.9 percent (P<0.001).There was a reduction in
the monthly rate of traffic injuries related to alcohol by 10.5 percent as
compared to before the law (P<0.001). Adding a linear time trend as a predictor,
the decrease was by 24.8 percent (P<0.001). CONCLUSIONS: Positive results
followed from this new 'zero-tolerance' law implemented in 2012 in Chile. Chile
experienced a significant reduction in alcohol-related traffic fatalities and
injuries, being a successful public health intervention.
PMID- 28413168
TI - Prevalence of HIV, HBV, and HCV and Related Risk Factors amongst Male Homeless
People in Lorestan Province, the West of Iran.
AB - BACKGROUND: Homeless people are at a higher risk of blood-born infectious
diseases. The aim of this study was to estimate the prevalence of HIV, HBV, HCV
and related risk factors among male homeless people. STUDY DESIGN: A cross
sectional study. METHODS: This study was conducted in Khorramabad City, western
Iran from January to June 2015. A pre-designed validated questionnaire was used
to collect the data on behavioral and other potential risk factors. Blood samples
were taken in order to diagnose HIV, hepatitis B and C infections. The prevalence
of HIV, hepatitis B, C and related risk factors was reported with a 95%
confidence interval (CI). RESULTS: The participants were 307 male homeless people
with a mean (+/-SD) age of 35.86 (+/-9.62) yr. The prevalence of HIV, HBs Ag, and
HCV Ab positive cases was 6.51% (95% CI: 4.23, 9.90), 0.98% (95% CI: 0.31, 3.00),
and 31.27% (26.31, 36.71), respectively. The prevalence of co-infections of HIV
and HCV Ab+ was 5.76% (95% CI: 1.34, 8.51). The most common recently used drugs
were heroin, methamphetamine, and opium with a prevalence of 44.30%, 41.04%, and
24.76%, correspondingly. CONCLUSIONS: According to this study, prevalence of HIV
and hepatitis C among homeless people was considerable. Abusing heroin,
methamphetamine, and industrial drugs was also significant. Considering the
association between drug abuse, HIV, and hepatitis C infections, planning for
effective control and preventive interventions is important in homeless people.
PMID- 28413170
TI - Selecting Strategies to Reduce High-Risk Unsafe Work Behaviors Using the Safety
Behavior Sampling Technique and Bayesian Network Analysis.
AB - BACKGROUND: High-risk unsafe behaviors (HRUBs) have been known as the main cause
of occupational accidents. Considering the financial and societal costs of
accidents and the limitations of available resources, there is an urgent need for
managing unsafe behaviors at workplaces. The aim of the present study was to find
strategies for decreasing the rate of HRUBs using an integrated approach of
safety behavior sampling technique and Bayesian networks analysis. STUDY DESIGN:
A cross-sectional study. METHODS: The Bayesian network was constructed using a
focus group approach. The required data was collected using the safety behavior
sampling, and the parameters of the network were estimated using Expectation
Maximization algorithm. Using sensitivity analysis and belief updating, it was
determined that which factors had the highest influences on unsafe behavior.
RESULTS: Based on BN analyses, safety training was the most important factor
influencing employees' behavior at the workplace. High quality safety training
courses can reduce the rate of HRUBs about 10%. Moreover, the rate of HRUBs
increased by decreasing the age of employees. The rate of HRUBs was higher in the
afternoon and last days of a week. CONCLUSIONS: Among the investigated variables,
training was the most important factor affecting safety behavior of employees. By
holding high quality safety training courses, companies would be able to reduce
the rate of HRUBs significantly.
PMID- 28413169
TI - Respiratory Effects of Simultaneous Exposure to Respirable Crystalline Silica
Dust, Formaldehyde, and Triethylamine of a Group of Foundry Workers.
AB - BACKGROUND: Foundry workers are occupationally exposed to hazardous substances
such as silica dusts and toxic gases. The aim of this study was to examine the
effects of simultaneous exposure to complex mixtures of silica dust,
formaldehyde, and triethylamine on lung function parameters. STUDY DESIGN: A
cross-sectional study. METHODS: This study was conducted on 55 male workers of
core making unit of a foundry plant (the case group) and 55 workers in a food
industry were enrolled as a control group in 2015. Workers were monitored for
personal exposure to crystalline silica respirable dust, according the NIOSH
method No.7602. The concentrations of formaldehyde and triethylamine were
measured using a PID instrument. Lung function tests were performed according to
the ERS/ATS standards. RESULTS: The mean concentrations of personal exposure to
silica dust, formaldehyde, and triethylamine in the core making workers were 0.23
mg/m3, 2.85 ppm, and 5.55 ppm and respective exposures of control subjects were
less than the LOD (limit of detection). There were significant associations
between exposure to silica dust and decreases in FVC (Forced vital capacity)
values (P<0.05). The findings showed a statistically significant synergistic
effect of silica dust and triethylamine on FVC values (P<0.05). CONCLUSIONS: The
mean exposure of all studied substances was higher than occupational exposure
limits. Synergistic effects of exposure to silica dust and triethylamine on some
lung function parameters were observed. Simultaneous exposure of foundry workers
to silica dust and triethylamine could impair lung function.
PMID- 28413171
TI - Comparison of Weibull and Lognormal Cure Models with Cox in the Survival Analysis
Of Breast Cancer Patients in Rafsanjan.
AB - BACKGROUND: Breast cancer is the most common cancer after lung cancer and the
second cause of death. In this study we compared Weibull and Lognormal Cure
Models with Cox regression on the survival of breast cancer. STUDY DESIGN: A
cohort study. METHODS: The current study retrospective cohort study was conducted
on 140 patients referred to Ali Ibn Abitaleb Hospital, Rafsanjan southeastern
Iran from 2001 to 2015 suffering from breast cancer. We determined and analyzed
the effective survival causes by different models using STATA14. RESULTS:
According to AIC, log-normal model was more consistent than Weibull. In the
multivariable Lognormal model, the effective factors like smoking, second -hand
smoking, drinking herbal tea and the last breast-feeding period were included. In
addition, using Cox regression factors of significant were the disease grade,
size of tumor and its metastasis (p-value<0.05). As Rafsanjan is surrounded by
pistachio orchards and pesticides applied by farmers, people of this city are
exposed to agricultural pesticides and its harmful consequences. The effect of
the pesticide on breast cancer was studied and the results showed that the effect
of pesticides on breast cancer was not in agreement with the models used in this
study. CONCLUSIONS: Based on different methods for survival analysis, researchers
can decide how they can reach a better conclusion. This comparison indicates the
result of semi-parametric Cox method is closer to clinical experiences evidences.
PMID- 28413172
TI - The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth
factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats.
AB - To understand metformin's effects on fibroblast growth factors (FGFs) and
fibroblast growth factor receptor 1 (FGFR1), we investigated circulating
fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes
mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was
detected to explain the possible mechanisms. T2DM was induced by feeding rats
with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ,
30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow;
diabetic rats (DM) were fed on high-fat diet supplemented with or without
metformin (METF) for 12 weeks (500 mg.kg-1.d-1). Biochemical parameters were
detected at the end of 24th weeks. FGFR1 expression and protein kinase B (Akt)
phosphorylation in the pancreas and visceral adipose tissues were detected using
either Western blot (WB) or immunohistochemistry (IHC). Serum FGF19 and FGF21
were measured using enzyme-linked immune sorbent assay (ELISA). Metformin treated
DM rats showed improved glucose, lipid and bile acid metabolism. Besides,
significantly decreased FGF19 and increased FGF21 were observed in DM+METF rats.
DM rats showed significantly increased FGFR1 both in the pancreas and visceral
adipose tissues. While in DM+METF rats, FGFR1 was almost remained at a normal
level in the pancreas and increased in the visceral adipose tissue compared to
that in DM rats. Besides, metformin treatment restores Akt phosphorylation in
both tissues. The altered glucose and lipid profiles by metformin treatment may
be associated with the increased circulating FGF21 and tissue-specific
expressions of FGFR1.
PMID- 28413173
TI - 25-Hydroxyvitamin D serum level in Hashimoto's thyroiditis, but not Graves'
disease is relatively deficient.
AB - Vitamin D is a modulator of both the innate and adaptive immune system. As
vitamin D deficiency was a risk factor for some autoimmune diseases, we aimed to
evaluate the serum vitamin D levels in autoimmune thyroid diseases (AITD)
including Graves' disease (GD) and Hashimoto's thyroiditis (HT) and investigated
the association between serum vitamin D levels and AITD. 175 AITD patients
including 51 GD, 61 euthyroid HT (mild HT), 63 euthyroid HT patients with
hypothyroidism receiving hormone therapy (treated HT) were recruited from the
outpatient department. 51 controls were from the physical checkup center of the
hospital. 25-Hydroxyvitamin D levels, thyroid function, antithyroid antibodies,
IL-4, IL-17, and TNF-alpha were determined. Compared with the controls, treated
and mild HT patients had significantly lower 25(OH)D levels (45.77+/-3.48 vs.
83.49+/-6.24 nmol/L, p<0.001) and (55.25+/-3.88 vs. 83.49+/-6.24 nmol/L,
p<0.001), respectively. However, GD patients had similar 25(OH)D levels (81.77+/
5.60 vs. 83.49+/-6.24 nmol/L, p=0.808). Compared to 24.1% controls with prevalent
vitamin D deficiency, mild HT and treated HT patients were significantly
different (55.4%, p<0.001) and (70.3%, p<0.001), respectively; no difference was
seen in the GD patients (22.9%, p=0.797). Serum 25(OH)D levels were not
associated with thyroid function, antithyroid antibodies, and serum cytokines IL
4, IL-17, and TNF-alpha in patients with AITD. We observed relatively low vitamin
D level in mild and treated HT patients, while GD patients had similar 25(OH)D
levels to those of healthy individuals. Further studies are imperative to explore
the complex etiology of vitamin D deficiency in AITD.
PMID- 28413174
TI - An outbreak of duck hepatitis A virus type 1 infection in Japan.
AB - In June 2015, a highly fatal and acute disease broke out in a duckling farm in
Hyogo Prefecture, Japan. The birds exhibited poor growth, reduced movement, lying
in a dorsal recumbent position, depression, lethargy, ataxia and opisthotonus,
with a high mortality rate of approximately 76%. By performing a reverse
transcription-polymerase chain reaction (RT-PCR) using primers specific for duck
hepatitis A virus type 1 (DHAV-1), we obtained the PCR products of a predicted
size. The nucleotide sequences of the PCR products showed a >96% identity with
that of the DHAV-1, HB02 strain, which was isolated in China. To our knowledge,
this is the first time that the DHAV-1 virus has been isolated since its outbreak
in Japan in 1963.
PMID- 28413175
TI - Prenatal postcranial development in two species of sympatric Japanese wood mice
(Apodemus argenteus and A. speciosus): a comparison of arboreal versus
terrestrial congeners.
AB - Habitats of two closely related Japanese field mice, Apodemus argenteus and A.
speciosus, broadly overlap in many Japanese forests. A. argenteus being more
arboreal and A. speciosus being more terrestrial, it is thought that such
ecological segregation allows their sympatric distribution. Comparing these two
congeners, whether ecological difference is reflected in postcranial development
was examined. Although overall ossification sequences were virtually identical,
development of the caudal vertebrae was remarkably earlier in A. argenteus. One
of the clearest morphological differences between the two species is the relative
length of the tail, which is arguably related to the degree of arboreality. I
suggest that accelerated ossification of the caudal vertebrae found in A.
argenteus is related to its elongation of the tail.
PMID- 28413176
TI - Investigating right ovary degeneration in chick embryos by transcriptome
sequencing.
AB - In asymmetric chick gonads, the left and right female gonads undergo distinct
programs during development, generating a functional ovary on the left side only.
Despite some progress being made in recent years, the mechanisms of molecular
regulation remain incompletely understood, and little genomic information is
available regarding the degeneration of the right ovary in the chick embryo
testis. In this study, we performed transcriptome sequencing to investigate
differentially expressed genes in the left and right ovaries and gene functions
at two critical time points; embryonic days 6 (E6) and 10 (E10). Using high
throughput RNA-sequencing technologies, 539 and 1046 genes were identified as
being significantly differentially expressed between 6R-VS-6L and 10R-VS-10L.
Gene ontology analysis of the differentially expressed genes revealed enrichment
in functional pathways. Among these, candidate genes associated with degeneration
of the right ovary in the chick embryo were identified. Identification of a
pathway involved in ovarian degeneration provides an important resource for the
further study of its molecular mechanisms and functions.
PMID- 28413177
TI - Exercise Transcutaneous Oximetry of the Buttocks - External Validation With
Computed Tomography Angiography.
AB - BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is a non-invasive test
for exercise-induced buttock ischemia. Prior study defined Ex-tcPO2
normal/abnormal cut-offs against arteriography but no external validation was
available. The aims of this study were therefore to (1) determine the diagnostic
performance of Ex-tcPO2 against CTA; (2) determine the cut-off point for
detection of stenosis >75% in arteries toward the hypogastric circulation; and
(3) determine the effect of chest profile classification on the diagnostic
performance of Ex-tcPO2.Methods and Results:A total of 207 patients referred for
Ex-tcPO2 were analyzed. DROP during Ex-tcPO2 was compared with the CTA results.
Chest-tcPO2 changes were automatically classified into pre-defined profiles
representing normal or abnormal responses. Using DROP <-15 mmHg as a cut-off, Ex
tcPO2 had 80.2% sensitivity, 72.3% specificity, 43.1% PPV, 93.3% NPV and 73.9%
accuracy, to detect 1 stenosis >75% in arteries toward the hypogastric
circulation. Optimal DROP to detect stenosis was: -15 mmHg. The overall
diagnostic performance of Ex-tcPO2 was independent of chest profile
classification. CONCLUSIONS: Ex-tcPO2 has satisfactory diagnostic performance to
detect arterial stenoses towards the hypogastric circulation. Abnormal chest
tcPO2 profile does not impair the overall diagnostic performance of the test.
PMID- 28413178
TI - Synthesized Abeta42 Caused Intracellular Oxidative Damage, Leading to Cell Death,
via Lysosome Rupture.
AB - Neuronal cellular accumulation of amyloid beta peptide (Abeta) has been
implicated in the pathogenesis of Alzheimer's disease (AD). Intracellular
accumulation of Abeta42, a toxic form of Abeta, was observed as an early event in
AD patients. However, its contribution and the cellular mechanism of cell death
remained unclear. We herein revealed the mechanism by which Abeta42 incorporated
into cells leads to cell death by using chemically synthesized Abeta42 variants.
The Abeta42 variant Abeta42 (E22P) which has an increased tendency to
oligomerize, accumulated in lysosomes at an earlier stage than wild-type Abeta42,
leading to higher ROS production and lysosomal membrane oxidation, and resulting
in cell death. On the other hand, Abeta42 (E22V), which is incapable of
oligomerization, did not accumulate in cells or affect the cell viability.
Moreover, intracellular localization of EGFP-Galectin-3, a beta-galactoside
binding lectin, showed that accumulation of oligomerized Abeta42 in lysosomes
caused lysosomal membrane permeabilization (LMP). Overexpression of lysosome
localized LAMP1-fused peroxiredoxin 1 and treatment with U18866A, an inhibitor of
cholesterol export from lysosomes that causes an increase in lysosomal membrane
stability, attenuated Abeta42-mediated LMP and cell death. Our findings show that
lysosomal ROS generation by toxic conformer of Abeta led to cell death via LMP,
and suggest that these events are potential targets for AD prevention.Key words:
Amyloid-beta (Abeta), Cell death, Lysosome, Lysosomal membrane permeabilization,
Reactive oxygen species (ROS).
PMID- 28413179
TI - Cyclic thrombocytopenia synchronizing with the menstrual cycle showing periodic
phases of thrombocytopenia and rebound thrombocytosis.
AB - A 37-year-old woman was admitted to our hospital for purpura involving the
extremities and thrombocytopenia. Prednisolone (PSL) was administered based on a
diagnosis of idiopathic thrombocytopenic purpura (ITP), but was not effective for
maintaining her platelet count within the normal range, which showed cyclic
fluctuation corresponding to the menstrual cycle. Therefore, we discontinued PSL,
and cyclic thrombocytopenia (CTP) was diagnosed. CTP is a rare disease which is
usually treated as ITP but with no response. Although the exact cause of CTP is
uncertain, in our case, a hormonal mechanism may be responsible for fluctuating
platelet count.
PMID- 28413180
TI - Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose
Lowering.
AB - AIM: Myriad biological effects of leptin may lead to broad therapeutic
applications for various metabolic diseases, including diabetes and its
complications; however, in contrast to its anorexic effect, the molecular
mechanisms underlying adipopenic and glucose-lowering effects of leptin have not
been fully understood. Here we aim to clarify the role of hormone-sensitive
lipase (HSL) in leptin's action. METHODS: Wild-type (WT) and HSL-deficient
(HSLKO) mice were made hyperleptinemic by two commonly-used methods: adenovirus
mediated overexpression of leptin and continuous subcutaneous infusion of leptin
by osmotic pumps. The amount of food intake, body weights, organ weights, and
parameters of glucose and lipid metabolism were measured. RESULTS:
Hyperleptinemia equally suppressed the food intake in WT and HSLKO mice. On the
other hand, leptin-mediated fat loss and glucose-lowering were significantly
blunted in the absence of HSL when leptin was overexpressed by recombinant
adenovirus carrying leptin. By osmotic pumps, the fat-losing and glucose-lowering
effects of leptin were milder due to lower levels of hyperleptinemia; although
the difference between WT and HSLKO mice did not reach statistical significance,
HSLKO mice had a tendency to retain more fat than WT mice in the face of
hyperleptinemia. CONCLUSIONS: We clarify for the first time the role of HSL in
leptin's effect using a genetic model: leptin-promoted fat loss and glucose
lowering are at least in part mediated via HSL-mediated lipolysis. Further
studies to define the pathophysiological role of adipocyte lipases in leptin
action may lead to a new therapeutic approach to circumvent leptin resistance.
PMID- 28413181
TI - Review of Past Reports and Current Concepts of Surgical Management for
Craniosynostosis.
AB - The purposes of surgery for craniosynostosis are to release increased
intracranial pressure and to normalize cranial shape. The procedure was developed
from a simple strip craniectomy in practice which ranged from the removal of the
fused suture before the 1960s to total calvarial remodeling after 1970s and later
methods of the 1990s, such as distraction and its modifications. According to its
history, craniofacial surgeons might be changing their procedures with more
effective, than less invasive ways. Since the late 1990s, when the distraction
was applied to the craniofacial surgery, the gradual expansion, in particular of
the anterior cranium, common in Japan, has long been controversial until the
Caucasians accepted its use for the posterior cranium. Currently, the method may
revert to the old procedure because a more sophisticated and better morphological
result can be obtained depending on the types of deformity, even if a little more
invasive maneuver is required. In other words, if treatment can be performed in
optimal time, the procedures that were developed in the last half a century
should be altered to each condition.
PMID- 28413182
TI - Introduction to the concept of signal toxicity.
AB - Silent Spring by Rachel Carson (1962) established a role for environmental
chemicals in cancer and Our Stolen Future by Theo Colbone, Dianne Dumanoski and
John Peterson Myers (1996) coined the concept of "Endocrine Disrupting Chemicals
(EDCs)" with its mechanistic plausibility for all the living organisms. For basic
biologists, seeing a non-monotonic dose-response curve was a matter of course. In
contrast, for the toxicologists at that time, the dose-response curves should be
monotonic. It took some time for toxicologists to accept the plausibility that
animals and humans are subject to the effects of EDCs act in a way that is
explained by the new paradigm of receptor-mediated toxicity or in other words
"signal toxicity." In classical toxicology, a toxic substance reaches a cellular
target and induces malfunction. The target molecules are proteins including
enzymes, lipid membranes, DNA, and other components of the cell which are damaged
by the toxic substances. On the other hand, in the case of signal toxicity, a
chemical binds to a specific receptor - after that, the chemical itself is not
important. The signal from the receptor initiates a cascade of molecular events
that leads to various changes in the cells and organs. When the signal is
abnormal for a cell or an organ in terms of quality, intensity and timing, then
the signal will induce adverse effects to the target. An extreme example of
signal toxicity is the 1981 Nobel Prize in Physiology or Medicine work by Drs.
Hubel and Wiesel. They blocked the signal of sharp images from the retina to the
brain and found that the visual cortex needed this signal at the correct time for
its proper development. In humans, such signal disruption is well known to induce
"form-deprivation amblyopia" in infants. The concept of signal toxicity widens
the range of systems vulnerable to EDCs and facilitates the understanding of
their biological characteristics. For example, compared with intrinsic ligands,
xenobiotic chemicals usually act as weak agonists and/or weak antagonists of
receptor systems; the dose-response characteristics and the dose range will
depend on the signaling system of concern. If the signal is used for
organogenesis and functional maturation, there would be a critical period in the
development during which the disturbance of such signals may cause irreversible
changes. Since recepter-based signaling mechanisms are usually an amplification
systems, it is hard to set a threshold in its dose response, and the outcome of
signal toxicity is often stochastic at low doses. This review attempts to explain
the benefits of incorporating the concept of signal toxicology for widening the
range of toxicology for the better protection of human and environmental health
in modern civilized life, where chemicals are designed to be less toxic in terms
of traditional toxicity but not yet in "signal toxicity."
PMID- 28413183
TI - A SLC24A2 Gene Variant Uncovered in Pancreatic Ductal Adenocarcinoma by Whole
Exome Sequencing.
AB - Pancreatic ductal adenocarcinoma (PDAC) presents as an aggressive malignancy
caused by environmental and genetic factors. In order to identify causal genes
for PDAC, we performed whole exome sequencing (WES) to detect gene mutations in
seven pairs of PDAC tissue and adjacent non-tumor tissue samples. Finally, we
found a new nonsynonymous single nucleotide variant (nsSNV) in solute carrier 24
family member 2 (SLC24A2) gene resulting in the substitution of native glutamic
acid (E) into aspartic acid (D) at position of 287 amino acid (E287D) in SLC24A2
protein, and confirmed this variant by Sanger gene sequencing. SLC24A2 is a
potassium-dependent sodium-calcium exchanger and can transport metal ion across
cell membrane. Multiple in silico variants' effects analyses methods including
SIFT, PolyPhen, PROVEAN, and PANTHER demonstrated this variant had probably
damaging effects, which was consistent with the results obtained from Mutation
Taster software analysis with a probability of 0.99999997 to be "disease
causing." The three dimension (3D) structure analysis results suggested this
variant had little effects on the solubility and hydrophobicity of the protein;
but it could decrease the protein stability by increasing the total protein
structure energy (-8874.33 kJ/mol for the mutant and -8963.54 kJ/mol for the
native) and by causing the mutant protein decreasing three stabilizing residues.
Less stability of the mutant 287D protein than the native E287 protein was also
supported by I-Mutant and Western-blotting analysis results. Overall, a new
mutation in SLC24A2 gene was identified to decrease the stability of SLC24A2,
which may have potential clinical usages.
PMID- 28413184
TI - Risk of Ischemic Stroke in Patients With Non-Valvular Atrial Fibrillation Not
Receiving Oral Anticoagulants - Korean Nationwide Population-Based Study.
AB - BACKGROUND: Atrial fibrillation, the most common cardiac arrhythmia, is
associated with an elevated thromboembolic risk, including ischemic stroke.
Guidelines recommend the stratification of individual stroke risk and tailored
antithrombotic therapy. This study investigated the demographics, comorbidities,
and prognosis of non-valvular AF (NVAF) in Korean patients.Methods and Results:We
extracted data on 10,846 patients with newly diagnosed NVAF who were naive to
oral anticoagulants from the National Health Insurance Service-National Sample
Cohort. CHADS2and CHA2DS2-VASc scores were calculated for each subject using
claims data. The study endpoints were ischemic stroke, thromboembolism, and
mortality. Mean age was 63.7 years, and 46.8% of the patients were women. Women
were older and had higher CHADS2and CHA2DS2-VASc scores. During 30,138 person
years of follow-up, ischemic stroke occurred at a rate of 2.95/100 person-years.
CHADS2and CHA2DS2-VASc scores showed good performance in risk prediction. CHA2DS2
VASc score performed better at discriminating stroke risk in patients with low
risk profiles. The presence of female sex and vascular disease added little
improvement in risk prediction. CONCLUSIONS: Korean NVAF patients had high risk
of stroke and mortality, and had multiple comorbidities. While both CHADS2and
CHA2DS2-VASc schema had good performance in risk prediction, CHA2DS2-VASc score
was superior in identifying truly low-risk patients. Given that Asian ethnicity
is associated with bleeding events, individualized accurate risk prediction is
necessary to improve patient outcomes.
PMID- 28413185
TI - Comparison of the Long-Term Outcomes of Mechanical and Bioprosthetic Aortic
Valves - A Propensity Score Analysis.
AB - BACKGROUND: The aim of this study was to assess the long-term outcomes of aortic
valve replacement (AVR) with either mechanical or bioprosthetic valves according
to age at operation.Methods and Results:A total of 1,002 patients (527 mechanical
valves and 475 bioprosthetic valves) undergoing first-time AVR were categorized
according to age at operation: group Y, age <60 years; group M, age 60-69 years;
and group O, age >=70 years). Outcomes were compared on propensity score analysis
(adjusted for 28 variables). Hazard ratio (HR) was calculated using the Cox
regression model with adjustment for propensity score with bioprosthetic valve as
a reference (HR=1). There were no significant differences in overall mortality
between mechanical and bioprosthetic valves for all age groups. Valve-related
mortality was significantly higher for mechanical valves in group O (HR, 2.53;
P=0.02). Reoperation rate was significantly lower for mechanical valves in group
Y (HR, 0.16; P<0.01) and group M (no events for mechanical valves). Although the
rate of thromboembolic events was higher in mechanical valves in group Y (no
events for tissue valves) and group M (HR, 9.05; P=0.03), there were no
significant differences in bleeding events between all age groups. CONCLUSIONS:
The type of prosthetic valve used in AVR does not significantly influence overall
mortality.
PMID- 28413187
TI - Noninvasive Fractional Flow Reserve Derived From Coronary Computed Tomography
Angiography - Is This Just Another New Diagnostic Test or the Long-Awaited Game
Changer?
AB - Despite the clinical importance of ischemia evaluation, obtaining fractional flow
reserve (FFR) value has, heretofore, only been available during invasive cardiac
catheterization. Although there is a clear linkage between morphology and
physiology, a significant gap still exists. FFR derived from coronary computed
tomography angiography (FFRCT) is a novel method of quantifying the hemodynamic
significance of coronary artery stenoses by translating morphological information
into hemodynamic data. Improved diagnostic performance of FFRCThas been
repeatedly demonstrated in comparison with coronary computed tomography
angiography alone with an invasive FFR reference standard. More recently, the
potential benefit of this technology to safely defer non-indicated
catheterizations and reduce healthcare costs has been established and indicates
this technology may improve the management of patients with coronary artery
disease. In this review, we summarize the scientific basis of FFRCTand evidence
from clinical trials, provide illustrative examples of clinical applications,
discuss potential limitations, and outline avenues for future research.
PMID- 28413186
TI - The characterization of a full-thickness excision open foot wound model in n5
streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer
in terms of reduced blood circulation, higher C-reactive protein, elevated
inflammation, and reduced cell proliferation.
AB - Delayed foot wound healing is a major complication attributed to hyperglycemia in
type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot
ulcers. There are at least two types of DM wound models used in rodents to study
delayed wound healing. However, clinically relevant animal models are not common.
Most models use type 1 DM rodents or wounds created on the back rather than on
the foot. An open full-thickness excision wound on the footpad of type 2 DM rats
is more clinically relevant, but such a model has not yet been characterized
systematically. The objective of this study was to investigate and characterize
how DM affected a full-thickness excision open foot wound in n5-streptozotocin
(n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation,
reduced blood circulation, and cell proliferation due to hyperglycemia could
delay the wound healing of DM rats. The wounds of DM rats were compared with
those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing
process of the DM rats was significantly delayed compared with that of the Ctrl
rats. The DM rats also had higher C-reactive protein (CRP) and lower blood
circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This
confirmed that elevated inflammation and reduced blood flow and cell
proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open
foot wound animal model provides a good approach to study the process of delayed
wound healing.
PMID- 28413188
TI - Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration
and Risk of Cardiovascular Events - Systematic Review and Meta-Analysis of
Prospective Studies.
AB - BACKGROUND: Previous studies have not found a consistent association between
circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) and the risk of
cardiovascular events. The aim of this meta-analysis was to evaluate this
association in prospective studies.Methods and Results:A systematic search of
prospective studies published through October 2016 was carried out in order to
identify studies that met pre-specified inclusion criteria. After independent
data extraction, summary relative risks were calculated using random-effects
models. On meta-analysis of 6 cohort and 1 nested case-control study, circulating
PCSK9 concentration as a continuous variable was not significantly associated
with the risk of cardiovascular events (overall RR, 1.12; 95% CI: 0.98-1.29;
P=0.09), with significant heterogeneity (I2=55.1%, Pheterogeneity=0.038). The
highest but not middle categories of circulating PCSK9 was significantly
associated with the risk of cardiovascular events. On subgroup analysis of study
design, mean age at baseline, sample size, follow-up time, and pre-existing
disease, there was no significant association between PCSK9 and cardiovascular
events. Sensitivity analysis with various exclusion and inclusion criteria did
not materially change the results. CONCLUSIONS: Circulating PCSK9 concentration
as a continuous variable was not significantly associated with the risk of
cardiovascular events. More well-designed studies are needed to clarify the role
of PCSK9 in cardiovascular risk.
PMID- 28413189
TI - Heart Transplantation in Asia.
AB - Heart transplantation (HTx) is the effective way to improve quality of life as
well as survival in terminal heart failure (HF) patients. Since the first heart
transplant in 1968 in Japan and in earnest in 1987 at Taiwan, HTx has been
continuously increasing in Asia. Although the current percentage of heart
transplants from Asia comprises only 5.7% of cases in the International Society
of Heart and Lung Transplantation (ISHLT) registry, the values were under
reported and soon will be greatly increased. HTx in Asia shows comparable with or
even better results compared with ISHLT registry data. Several endemic
infections, including type B hepatitis, tuberculosis, and cytomegalovirus, are
unique aspects of HTx in Asia, and need special attention in transplant care.
Although cardiac allograft vasculopathy (CAV) is considered as a leading cause of
death after HTx globally, multiple observations suggest less prevalence and
benign nature of CAV among Asian populations. Although there are many obstacles
such as religion, social taboo or legal process, Asian countries will keep
overcoming obstacles and broaden the field of HTx.
PMID- 28413190
TI - Virgin Olive Oil Enriched with Lutein-Zeaxanthin from Spinacia oleracea.
AB - The aim of this work consists of developing a technological process for
elaborating a virgin olive oil enriched in lutein-zeaxanthin extracted from
spinach, studying different parameters like temperature, time of extraction and
different ratios (spinach-oil). It was observed that the amount of carotenoids
extracted increased up to a maximum after 24 hours and decreased as the
maceration time progressed up to 60 hours, resulting of biological degradation.
It was also observed that as more spinach we added, as more lutein-zeaxanthin in
the enriched virgin olive oil was obtained. The best results were obtained after
24 hours by using a 75:25 ratio at 30 degrees C. Values of oxidative stability
decreased drastically, as well as other parameters such as acidity; peroxides
index and Ks were modified when the enriched virgin olive oil was subjected to 45
degrees C for 24 hours of maceration. Thus, the present procedure constitutes a
way to achieve an increase in the daily intake of beneficial compounds.
PMID- 28413191
TI - Length-scale Specific Crystalline Structural Changes Induced by Molecular
Randomization of Pequi Oil.
AB - Pequi fruit (Caryocar brasiliense Camb) is considered important since its pulp
has a high content of oil and carotenoids. The oil's triacylglycerols (TAGs)
contain mainly oleic (~57%) and palmitic (~36%) fatty acids, distributed
primarily among POO, POP/PPO, and OOO TAGs. It displays a tendency to fractionate
upon storage and has a relatively low melting temperature (SFC of 4% at 25
degrees C). Pequi oil was modified through chemical interesterification, which
increased the PPP content to ~6%. This caused a flattening in the SFC-temperature
profile, raising the end of melt temperature significantly (SFC of 4% at 39
degrees C). The interesterified oil does not fractionate and is thermally stable
up to 40 degrees C, with an SFC-temperature profile resembling that of roll-in
shortening (SFC of 31% at 16 degrees C) despite containing high amounts of oleic
acid. Crystallization and melting behavior changed. Crystal packing became more
disorganized as evidenced by a significant decrease in crystalline domain size in
the [001] direction from 42.3 nm to 32.1 nm. Polymorphism remained of the
triclinic (beta) subcell type but polytypism changed from the 3L to the 2L type.
Polarized light microscopy demonstrated that interesterification dramatically
decreased crystal size, consistent with a higher rate of nucleation in the
material. Moreover, the dramatic improvement in physical stability and
functionality was not accompanied by a significant decrease in total carotenoid
content (~390 mg/kg).
PMID- 28413192
TI - Secondary Structural Changes of Intact and Disulfide Bridges-Cleaved Human Serum
Albumins in Thermal Denaturation up to 130 degrees C - Additive Effects of Sodium
Dodecyl Sulfate on the Changes.
AB - The secondary structural changes of human serum albumin with the intact 17
disulfide bridges (HSA) and the disulfide bridges-cleaved human serum albumin
(RCM-HSA) in thermal denaturation were examined. Most of the helical structures
of HSA, whose original helicity was 66%, were sharply disrupted between 50 and
100 degrees C. However, 14% helicity remained even at 130 degrees C. The
temperature dependence of the degree of disrupted helical structures of HSA was
discussed in connection with questions about a general protein denaturation
model. When HSA lost the disulfide bridges, about two-thirds of the original
helices were disrupted. Although the helices of RCM-HSA remaining after the
cleavage of the disulfide bridges were relatively resistant against the heat
treatment, the helicity changed from 22% at 25 degrees C to 14% at 130C. The
helicity of RCM-HSA at 130 degrees C agreed with the helicity of HSA at the same
temperature, indicating that the same helical moieties of the polypeptides
remained unaffected at this high temperature. The additive effects of sodium
dodecyl sulfate (SDS) on the structural changes of HSA and RCM-HSA in thermal
denaturation were also examined. A slight amount of SDS protected the helical
structures of HSA from thermal denaturation below 80 degrees C. Upon cooling to
25 degrees C after heat treatment at temperatures below 70 degrees C with the
coexistence of SDS of low concentrations, the helical structures of HSA were
reformed to the original level at 25 degrees C before heating. A similar tendency
was also observed after heat treatment at 80 degrees C. In contrast, the helical
structures of the RCM-HSA complexes with SDS are completely recovered upon
cooling to 25 degrees C even after heat treatment up to 100 degrees C. Similar
investigations were also carried out on bovine serum albumins which had the
intact 17 disulfide bridges and lost all of the bridges.
PMID- 28413193
TI - Effect of Dietary Purified Xanthohumol from Hop (Humulus lupulus L.) Pomace on
Adipose Tissue Mass, Fasting Blood Glucose Level, and Lipid Metabolism in KK-Ay
Mice.
AB - We previously showed that xanthohumol-rich hop extract (XRHE, ~18% xanthohumol)
exerts anti-obesity effects in rats fed a high-fat diet through regulation of
fatty acid metabolism. In this study, we examined the effects of dietary purified
xanthohumol from XRHE (PX, ~91.9% xanthohumol) in KK-Ay mice in order to
understand the anti-obesity effects of xanthohumol alone because XRHE contains
82% unknown compounds. Dietary consumption of PX significantly inhibited an
increase in the visceral fat weight of mice compared to those fed control diet
without PX. Plasma leptin level was significantly lower in the PX-fed group than
in the control group. Dietary PX lowered hepatic fatty acid synthesis by down
regulation of SREBP1c mRNA expression in the liver. On the other hand, fatty acid
beta-oxidation in the liver was promoted by dietary PX through the up-regulation
of PPARalpha mRNA expression. Moreover, the fecal levels of fatty acids and
carbohydrates increased by dietary PX. PX inhibited lipase or alpha-amylase
activity in vitro. Thus, we found that PX may exert anti-obesity effects through
the regulation of lipid metabolism and inhibition of intestinal fat and
carbohydrate absorption, and that xanthohumol alone may exert anti-obesity
effects.
PMID- 28413195
TI - Purinergic signaling in microglia in the pathogenesis of neuropathic pain.
AB - Nerve injury often causes debilitating chronic pain, referred to as neuropathic
pain, which is refractory to currently available analgesics including morphine.
Many reports indicate that activated spinal microglia evoke neuropathic pain. The
P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in
spinal microglia after nerve injury by several factors, including CC chemokine
receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord,
interferon regulatory factor 8 (IRF8) and IRF5. Inhibition of P2X4R function
suppresses neuropathic pain, indicating that microglial P2X4R play a key role in
evoking neuropathic pain.
PMID- 28413194
TI - Dual role of cellular prion protein in normal host and Alzheimer's disease.
AB - Using PrPC-knockout cell lines, it has been shown that the inhibition of
apoptosis through STI1 is mediated by PrPC-dependent SOD activation. Antioxidant
PrPC may contribute to suppression of inflammasome activation. PrPC is
functionally involved in copper metabolism, signal transduction, neuroprotection,
and cell maturation. Recently several reports have shown that PrPC participates
in trans-membrane signaling processes associated with hematopoietic stem cell
replication and neuronal differentiation. In another role, PrPC also tends to
function as a neurotoxic protein. Abeta oligomer, which is associated with
neurodegeneration in Alzheimer's disease (AD), has also been reported to act as a
ligand of PrPC. However, the physiological role of PrPC as an Abeta42-binding
protein is not clear. Actually, PrPC is critical in Abeta42-mediated autophagy in
neurons. PrPC shows a beneficial role in lipid rafts to promote autophagy.
Further search for PrPC-interaction molecules using Prnp-/- mice and various
types of Prnp-/- cell lines under various conditions may elucidate other
important PrPC important functions.
PMID- 28413196
TI - The molecular cues regulating immune cell trafficking.
AB - Lymphocyte recirculation between the blood and the lymphoid/non-lymphoid tissues
is an essential homeostatic mechanism that regulates humoral and cellular immune
responses in vivo. This system promotes the encounter of naive T and B cells with
their specific cognate antigen presented by dendritic cells, and with the
regulatory cells with which they need to interact to initiate, maintain, and
terminate immune responses. The constitutive lymphocyte trafficking is mediated
by particular types of blood vessels, including the high endothelial venules
(HEVs) in lymph nodes and Peyer's patches, and the flat-walled venules in non
lymphoid tissues including the skin. The lymphocyte migration across HEVs
involves tethering/rolling, arrest/firm adhesion/intraluminal crawling, and
transendothelial migration. On the other hand, relatively little is known about
how lymphocytes and other types of cells migrate across the venules of non
lymphoid tissues. Here we summarize recent findings about the molecular
mechanisms that govern immune cell trafficking, including the roles of chemokines
and lysophospholipids in regulating immune cell motility and endothelial
permeability.
PMID- 28413198
TI - Engineering the lodging resistance mechanism of post-Green Revolution rice to
meet future demands.
AB - Traditional breeding for high-yielding rice has been dependent on the widespread
cultivation of gibberellin (GA)-deficient semi-dwarf varieties. Dwarfism lowers
the "center of gravity" of the plant body, which increases resistance against
lodging and enables plants to support high grain yield. Although this approach
was successful in latter half of the 20th century in rice and wheat breeding,
this may no longer be enough to sustain rice with even higher yields. This is
because relying solely on the semi-dwarf trait is subject to certain limitations,
making it necessary to use other important traits to reinforce it. In this
review, we present an alternative approach to increase lodging resistance by
improving the quality of the culm by identifying genes related to culm quality
and introducing these genes into high-yielding rice cultivars through molecular
breeding technique.
PMID- 28413197
TI - Structure and function of Helicobacter pylori CagA, the first-identified
bacterial protein involved in human cancer.
AB - Chronic infection with Helicobacter pylori cagA-positive strains is the strongest
risk factor of gastric cancer. The cagA gene-encoded CagA protein is delivered
into gastric epithelial cells via bacterial type IV secretion, where it undergoes
tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Delivered
CagA then acts as a non-physiological scaffold/hub protein by interacting with
multiple host signaling molecules, most notably the pro-oncogenic phosphatase
SHP2 and the polarity-regulating kinase PAR1/MARK, in both tyrosine
phosphorylation-dependent and -independent manners. CagA-mediated manipulation of
intracellular signaling promotes neoplastic transformation of gastric epithelial
cells. Transgenic expression of CagA in experimental animals has confirmed the
oncogenic potential of the bacterial protein. Structural polymorphism of CagA
influences its scaffold function, which may underlie the geographic difference in
the incidence of gastric cancer. Since CagA is no longer required for the
maintenance of established gastric cancer cells, studying the role of CagA during
neoplastic transformation will provide an excellent opportunity to understand
molecular processes underlying "Hit-and-Run" carcinogenesis.
PMID- 28413199
TI - Rapid and coordinated processing of global motion images by local clusters of
retinal ganglion cells.
AB - Even when the body is stationary, the whole retinal image is always in motion by
fixational eye movements and saccades that move the eye between fixation points.
Accumulating evidence indicates that the brain is equipped with specific
mechanisms for compensating for the global motion induced by these eye movements.
However, it is not yet fully understood how the retina processes global motion
images during eye movements. Here we show that global motion images evoke novel
coordinated firing in retinal ganglion cells (GCs). We simultaneously recorded
the firing of GCs in the goldfish isolated retina using a multi-electrode array,
and classified each GC based on the temporal profile of its receptive field (RF).
A moving target that accompanied the global motion (simulating a saccade
following a period of fixational eye movements) modulated the RF properties and
evoked synchronized and correlated firing among local clusters of the specific
GCs. Our findings provide a novel concept for retinal information processing
during eye movements.
PMID- 28413200
TI - The oral microbiome community variations associated with normal, potentially
malignant disorders and malignant lesions of the oral cavity.
AB - The human oral microbiome has been known to show strong association with various
oral diseases including oral cancer. This study attempts to characterize the
community variations between normal, oral potentially malignant disorders (OPMD)
and cancer associated microbiota using 16S rDNA sequencing. Swab samples were
collected from three groups (normal, OPMD and oral cancer) with nine subjects
from each group. Bacteria genomic DNA was isolated in which full length 16S rDNA
were amplified and used for cloned library sequencing. 16S rDNA sequences were
processed and analysed with MOTHUR. A core oral microbiome was identified
consisting of Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes and
Actinobacteria at the phylum level while Streptococcus, Veillonella, Gemella,
Granulicatella, Neisseria, Haemophilus, Selenomonas, Fusobacterium, Leptotrichia,
Prevotella, Porphyromonas and Lachnoanaerobaculum were detected at the genus
level. Firmicutes and Streptococcus were the predominant phylum and genus
respectively. Potential oral microbiome memberships unique to normal, OPMD and
oral cancer oral cavities were also identified. Analysis of Molecular Variance
(AMOVA) showed a significant difference between the normal and the cancer
associated oral microbiota but not between the OPMD and the other two groups.
However, 2D NMDS showed an overlapping of the OPMD associated oral microbiome
between the normal and cancer groups. These findings indicated that oral microbes
could be potential biomarkers to distinguish between normal, OPMD and cancer
subjects.
PMID- 28413201
TI - Detection of alpha-thalassaemia in neonates on cord blood and dried blood spot
samples by capillary electrophoresis.
AB - INTRODUCTION: Haemoglobin Bart's (Hb Bart's) level is associated with alpha
thalassaemia traits in neonates, enabling early diagnosis of alpha-thalassaemia.
The study aimed to detect and quantify the Hb Bart's using Cord Blood (CB) and CE
Neonat Fast Hb (NF) progammes on fresh and dried blood spot (DBS) specimen
respectively by capillary electrophoresis (CE). METHODS: Capillarys Hemoglobin
(E) Kit (for CB) and Capillarys Neonat Hb Kit (for NF) were used to detect and
quantify Hb Bart's by CE in fresh cord blood and dried blood spot (DBS) specimens
respectively. High performance liquid chromatography (HPLC) using the beta-Thal
Short Programme was also performed concurrently with CE analysis. Confirmation
was obtained by multiplex ARMS Gap PCR. RESULTS: This study was performed on 600
neonates. 32/600 (5.3%) samples showed presence of Hb Bart's peak using the NF
programme while 33/600 (5.5%) were positive with CB programme and HPLC methods.
The range of Hb Bart's using NF programme and CB programme were (0.5-4.1%) and
(0.5-7.1%), respectively. Molecular analysis confirmed all positive samples
possessed alpha-thalassaemia genetic mutations, with 23/33 cases being
alphaalpha/--SEA, four -alpha3.7/-alpha3.7, two alphaalpha/-alpha3.7 and three
alphaalpha/alphaalphaCS. Fifty Hb Bart's negative samples were randomly tested
for alpha-genotypes, three were also found to be positive for alpha-globin gene
mutations. Thus, resulting in sensitivity of 91.7% and 88.9% and specificity of
100% for the Capillarys Cord Blood programme and Capillarys Neonat Fast programme
respectively. CONCLUSION: Both CE programmes using fresh or dried cord blood were
useful as a screening tool for alpha-thalassaemia in newborns. All methods show
the same specificity (100%) with variable, but acceptable sensitivities in the
detection of Hb Bart.
PMID- 28413202
TI - Conventional versus molecular detection of Chlamydia trachomatis and Neisseria
gonorrhoeae among males in a sexually transmitted infections clinic.
AB - BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae are important
bacterial pathogens of sexually transmitted infections (STIs) worldwide. This
study sought to compare the analytical sensitivity and specificity of
conventional methods against a rapid molecular method in detecting STIs caused by
these bacteria. METHODS: Ninety five first-time male attendees of the Genito
urinary Medicine Clinic in Hospital Kuala Lumpur were included in this cross
sectional study. The detection of C. trachomatis was achieved through direct
fluorescence antibody (DFA) staining of urethral swabs and real-time polymerase
chain reaction testing (Xpert(r) CT/NG assay) on urine specimens. N. gonorrhoeae
was detected through Gram staining and culture of urethral swabs and Xpert(r) CT/
NG assay on urine specimens. RESULTS: From the Xpert(r) CT/NG results, 11 (11.6%)
attendees had chlamydia, 23 (24.2%) had gonorrhoea and 8 (8.4%) had both STIs.
The sensitivity and specificity of DFA in detecting chlamydia compared to
Xpert(r) CT/NG were 5.3% (95% CI: 0-28) and 94.7% (95% CI: 86-98), respectively.
For gonorrhoea, the sensitivity and specificity of Gram staining were 90.3% (95%
CI: 73-98) and 95.3% (86-99), respectively, whereas the sensitivity and
specificity of culture compared to Xpert(r) CT/NG were 32.2% (95% CI: 17-51) and
100% (95% CI: 93-100), respectively. CONCLUSION: Although Gram-stained urethral
swab smears are sensitive enough to be retained as a screening tool for
gonorrhoea, culture as well as DFA lack sensitivity and are poorly suited to
screen for gonorrhoea and chlamydia, respectively. However, owing to their high
specificity, conventional detection methods are still suitable as confirmatory
tests for gonorrhoea and chlamydia.
PMID- 28413203
TI - Nuclear morphometry and texture analysis on cytological smears of thyroid
neoplasms: a study of 50 cases.
AB - BACKGROUND: Fine needle aspiration cytology (FNAC) is a reliable and reproducible
diagnostic technique for thyroid lesions with certain limitations. Computed
morphometric methods have been introduced with a view to improve the diagnostic
yield of thyroid aspirates. However, a review of the existing literature revealed
conflicting reports regarding morphometric parameters in thyroid neoplasms.
MATERIALS AND METHODS: This study included 50 cases of thyroid lesions (20 cases
of colloid goitre, 15 of follicular adenoma, 5 of follicular carcinoma and 10
papillary carcinomas). Digital images of cytologic smears of these cases were
captured using a dedicated photomicrography system and nuclear profiles traced
manually. With self-designed image analysis software, nuclear morphometric
measurements, including texture analysis, were performed. Discriminant analysis
was performed including the morphometric parameters and percentage of correctly
classified nuclei noted. RESULTS: Nuclear morphometry parameters showed that
papillary thyroid carcinoma had the highest perimeter, area, radius and
elongation factor compared to other thyroid lesions. Discriminant analysis
revealed that altogether 77.9% of cells could be correctly classified to their
lesion category based on the nuclear morphometric and textural parameters. Of the
neoplastic cases, 84.5% of cells of follicular neoplasms and 72.5% of papillary
carcinoma were classified to the respective category. CONCLUSION: Nuclear
morphometry, including texture analysis, can assist in the cytologic diagnosis of
thyroid lesions, considering the high degree of accuracy of classification.
Further studies and methodological refinements can achieve higher accuracy.
PMID- 28413204
TI - The study of the circannual relationship between the activity of the epiphysis
and gonads in rats of different sex and age.
AB - BACKGROUND: The relationship between the activity of the epiphysis and gonads in
rats of different sex and age in different seasons of the year was determined by
studying the levels of melatonin and testosterone in the blood plasma.
Determination of the levels of melatonin and testosterone in the serum of rats
was carried out by enzyme-linked immunosorbent assay. To assess the relationship
between the levels of melatonin and testosterone the correlation coefficient was
calculated. Based on the study of the levels of melatonin and testosterone in
serum the circannual relationship between the activity of the pineal gland and
gonads in males of reproductive age has been determined. In females, the
relationship between the levels of melatonin and testosterone without the
circannual dependence has been determined. The strongest correlation between
melatonin and testosterone is present in males at the age of 9 months in autumn,
and it corresponds to the human age of 29-30 years.
PMID- 28413205
TI - Oral ketamine induced pathological changes of the urinary tract in a rat model.
AB - INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to
cause urinary tract damage. However, there is little information on the
pathological effects of ketamine from oral administration. We aimed to study the
effects of oral ketamine on the urinary tract and the reversibility of these
changes after cessation of ketamine intake. METHODS: Rats were fed with illicit
(a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg
(N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding
for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for
any potential recovery of pathological changes before being sacrificed for
necropsy. Histopathological examination was performed on the kidney and urinary
bladder. RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed
with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the
control and 100 mg/kg illicit ketamine groups. Renal changes, such as
interstitial nephritis and papillary necrosis, were observed in rats given
illicit ketamine. After ketamine cessation, no inflammation was observed in the
bladder of all rats. However, renal inflammation remained in 60% of the rats
given illicit ketamine. No dose-effect relationship was established between oral
ketamine and changes in the kidneys. CONCLUSION: Oral ketamine caused
pathological changes in the urinary tract, similar to that described in exposure
to parenteral ketamine. The changes in the urinary bladder were reversible after
short-term exposure.
PMID- 28413206
TI - Differential diagnostic significance of HBME-1, CK19 and S100 in various thyroid
lesions.
AB - OBJECTIVE: Due several overlapping histomorphological features and pitfalls in
thyroid pathology, there is need to establish a panel of immunomarkers that would
aid in proper diagnosis. This study was carried out to investigate the ability of
HBME-1, CK19, and S100 in differentiating between hyperplastic, benign and
malignant thyroid lesions. MATERIALS AND METHODS: Immunohistochemical analysis of
60 thyroidectomy specimens (10 hyperplastic nodules, 14 follicular adenomas and
36 malignant thyroid neoplasms) was carried out. The extent and intensity of HBME
1, CK19, and S100 immunoreactivity was assessed in each case. RESULTS: HBME-1
positivity was noted in 86.1% of malignant cases while the majority of the benign
lesions were negative. Diffuse strong CK19 positivity was documented in 27/31
papillary carcinoma whereas all cases of follicular carcinoma and medullary
carcinoma were negative. Most of the hyperplastic nodules and follicular adenomas
were also CK19 negative, although focal weak staining was noted in a few cases.
S100 was positive only in medullary carcinoma. HBME-1 was most sensitive (86.1%)
and specific (87.5%) in distinguishing between benign and malignant thyroid
lesions. The diagnostic accuracy was further increased when HBME-1 was used
simultaneously with CK19/S100/CK19+S100. The sequential use of HBME-1 and CK19
also proved beneficial in discriminating between the various follicular-patterned
thyroid lesions. CONCLUSION: HBME-1 immunolabeling suggests malignancy, whereas
strong diffuse CK19 positivity substantiates papillary differentiation. The
utilization of these markers (alone or in combination) along with
histomorphological evaluation is helpful in the differential diagnosis. S100 has
minimal utility in this regard.
PMID- 28413207
TI - Rate of active Helicobacter pylori infection among symptomatic patients of
Pakistan.
AB - Only few epidemiological studies have examined the rate of active H. pylori
infection in the symptomatic population in Pakistan. This retrospective study
presents the laboratory data collected during the past 13 years (2002 to 2015)
from 2315 symptomatic patients referred to the BreathMAT Lab, Nuclear Medicine,
Oncology and Radiotherapy Institute, Islamabad for the diagnosis of active H.
pylori infection using the 13C Urea Breath Test. Rate of infection and its
association with gender and age were evaluated. The overall rate of active H.
pylori infection was 49.5% and there was no association of this rate of infection
with gender. An increase in rate of infection was observed with increasing age
with significant difference (p < 0.05). The patients that tested negative for
this infection might be having symptoms due to stress and indiscriminate use of
non-steroidal antiinflammatory drugs (NSAIDs) in this community. The fact that
half of the symptomatic patients were negative needs to be highlighted and
further suggests that symptomatic patients should be tested by the 13C UBT before
prescribing antibiotic treatment for H. pylori eradication. In addition, there is
a need to educate this community about the harmful and side effects of self
medication and overuse of NSAIDs.
PMID- 28413208
TI - Anti-M induced severe haemolytic disease of foetus and newborn in a Malay woman
with recurrent pregnancy loss.
AB - Haemolytic disease of the foetus and newborn (HDFN) is caused by maternal red
blood cells (RBC) alloimmunisation resulted from incompatibility of maternal and
foetal RBCs. However, only a few HDFN attributed to anti-M were reported, varying
from asymptomatic to severe anaemia with hydrops foetalis and even intrauterine
death. A case of severe HDFN due to anti-M alloantibody from an alloimmunized
grandmultiparous Malay woman with recurrent pregnancy loss is reported here. The
newborn was delivered with severe and prolonged anaemia which required frequent
RBC transfusions, intensive phototherapy and intravenous immunoglobulin
administration. Although anti-M is rarely known to cause severe HDFN, a careful
serological work-up and close assessment of foetal well-being is important,
similar to the management of RhD HDFN. Alloimmunisation with anti-M type can lead
to severe HDFN and even foetal loss.
PMID- 28413209
TI - Duplication 17p11.2 (Potocki-Lupski Syndrome) in a child with developmental
delay.
AB - Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome,
trisomy 17p11.2 or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and
a rare contiguous gene syndrome affecting 1 in 20,000 live births. Among the key
features of such patients are autism spectrum disorder, learning disabilities,
developmental delay, attention-deficit disorder, infantile hypotonia and
cardiovascular abnormalities. Previous studies using microarray identified
variations in the size and extent of the duplicated region of chromosome 17p11.2.
However, there are a few genes which are considered as candidates for PTLS which
include RAI1, SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In this report, we
investigated a case of a 3-year-old girl who has developmental delay. Her
chromosome analysis showed a normal karyotype (46,XX). Analysis using array CGH
(4X44 K, Agilent USA) identified an ~4.2 Mb de novo duplication in chromosome
17p11.2. The result was confirmed by fluorescence in situ hybridization (FISH)
using probes in the critical PTLS region. This report demonstrates the importance
of microarray and FISH in the diagnosis of PTLS.
PMID- 28413210
TI - Acute pulmonary thromboembolism in a case of fatal child abuse.
AB - Child abuse is a worldwide problem. The four major types of abuse include
physical abuse, child neglect, psychological maltreatment and sexual violence. We
describe a fatal case of child abuse which presented with numerous old and recent
soft tissue injuries all over the body. The injuries on the legs have immobilized
the victim for quite some time, giving rise to deep vein thrombosis, leading to
death as a result of acute pulmonary thromboembolism. This case demonstrates
presence of both elements of abuse and neglect in one victim. As this category of
crime involves a helpless child, we would also like to reiterate that the
community has an obligation to prevent such tragedies and educating the public to
recognize the signs and symptoms of abuse would be of utmost important.
Ultimately, the community must also be responsible for reporting such offences
and the act of silence is akin to condoning a crime witnessed.
PMID- 28413211
TI - Vaginal Brenner tumor with literature review: does this tumour originate from
Walthard nests?
AB - Vaginal Brenner tumor is extremely rare. Only five cases have been reported in
the English literature to date. Here we report a vaginal Brenner tumor in a 76
year old postmenopausal woman, who presented with a 2.5cm-sized sessile vaginal
polyp. Microscopically, it showed characteristic features of Brenner tumor
consisting of three components; transitional islands, glands, and dense fibrous
stroma. The epithelial tumor cells were positive for GATA-3, p63 and ER, but
negative for PAX8. The origin of Brenner tumors in the vagina is unclear, but
previous reports suggested of Mullerian origin. However, our case revealed that
vaginal Walthard nests could be possible precursor lesions based on their
immunohistochemical staining results.
PMID- 28413212
TI - Prevalence of BRAFV600E mutation in Asian patients with thyroid cancer.
AB - No abstract available.
PMID- 28413213
TI - Response: Prevalence of BRAFV600E mutation in Asian patients with thyroid cancer.
AB - No abstract available.
PMID- 28413214
TI - Circulating Biomarkers for Predicting Infliximab Response in Rheumatoid
Arthritis: A Systematic Bioinformatics Analysis.
AB - BACKGROUND Infliximab shows good efficacy in treating refractory rheumatoid
arthritis (RA). However, many patients responded poorly and related studies were
inconsistent in predictive biomarkers. This study aimed to identify circulating
biomarkers for predicting infliximab response in RA. MATERIAL AND METHODS Public
databases of Gene Expression Omnibus (GEO) and ArrayExpress were searched for
related microarray datasets, focused on the response to infliximab in RA. All
peripheral blood samples were collected before infliximab treatment and gene
expression profiles were measured using microarray. Differential genes associated
with infliximab efficacy were analyzed. The genes recognized by half of the
datasets were regarded as candidate biomarkers and validated by prospective
datasets. RESULTS Eight microarray datasets were identified with 374 blood
samples of RA patients, among which 191 (51.1%) were diagnosed as non-responders
in the subsequent infliximab treatment. Five genes (FKBP1A, FGF12, ANO1, LRRC31,
and AKR1D1) were associated with the efficacy and recognized by half of the
datasets. The 5-gene model showed a good predictive power in random- and
prospective-designed studies, with AUC (area under receiver operating
characteristic [ROC] curve)=0.963 and 1.000, and it was also applicable at the
early phase of treatment (at week 2) for predicting the response at week 14
(AUC=1.000). In the placebo group, the model failed to predict the response
(AUC=0.697), indicating the model's specificity in infliximab treatment.
CONCLUSIONS The model of FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1 in peripheral
blood is useful for efficiently predicting the response to infliximab treatment
in rheumatoid arthritis.
PMID- 28413215
TI - Successful Withdrawal of Insulin Therapy After Post-Treatment Clearance of
Hepatitis C Virus in a Man with Type 2 Diabetes.
AB - BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with increased
insulin resistance and risk of type 2 diabetes. Successful antiviral treatment
can improve insulin resistance and allow a reduction in blood glucose-lowering
treatment. There have been case reports of a reduced insulin requirement in this
situation, although 1 case in which insulin was stopped exhibited a subsequent
deterioration in glycemic control. CASE REPORT A 55-year-old Italian man was
diagnosed with HCV infection in 2000 at the age of 39 years and with type 2
diabetes 6 years later. He was started on metformin but progressed to multiple
daily insulin injections after 3 years. He was treated with pegylated interferon,
ribavirin, and telaprevir over 12 months from early 2013, and achieved a
sustained virologic response and normalization of hepatic function within 6
months of starting therapy. He was subsequently able to reduce his insulin doses
from 0.56 to 0.44 U/kg/day over the next 2 years and, based on a random serum C
peptide of 1.73 nmol/L (fasting reference range 0.37-1.47 nmol/L) in the presence
of serum glucose 7.9 mmol/L (143 mg/dL) and negative glutamic acid decarboxylase
antibodies, he accelerated withdrawal and stopped insulin 6 months later. He is
currently taking linagliptin 5 mg daily with good glycemic control. His body mass
index and HbA1c have remained <25 kg/m2 and <6.0% (<42 mmol/mol), respectively,
throughout. CONCLUSIONS This case shows that complete withdrawal of long-term
insulin therapy may be possible after HCV treatment has induced a sustained
virologic response.
PMID- 28413216
TI - Uncompromised NK cell activation is essential for virus-specific CTL activity
during acute influenza virus infection.
AB - Natural killer (NK) cells are indispensable components of both the innate and
adaptive immune response. However, their precise roles in the cross-talk between
innate and adaptive immunity during influenza virus infection remain
controversial. By comparing NK cell dynamics and activity under a sub-lethal dose
and high dose of influenza virus infection, we showed that influenza virus PR8
directly infected NK cells during natural infection, which was consistent with
our previous findings obtained from an in vitro investigation of human NK cells.
The impairments in cytotoxicity and IFN-gamma production by spleen NK cells
following high-dose infection were accompanied by decreased virus-specific
killing mediated by cytotoxic T lymphocytes (CTLs). Importantly, the weakened CTL
activity could be reversed by adoptive transfer of spleen NK cells harvested from
low-dose-infected mice but not healthy donors. Taken together, our data provide
direct evidence supporting the contribution of NK cells to antiviral T-cell
responses. This study also indicates that a novel NK-targeted immune evasion
strategy is used by influenza virus to shrink both innate and adaptive immune
responses.
PMID- 28413218
TI - Understanding how low-socioeconomic status households cope with health shocks: An
analysis of multi-sector linked data.
AB - Low-socioeconomic status (SES) households have little income or wealth to buffer
against the negative impacts of an adverse health event (health shock) among
adult household members. However, these households may employ a variety of other
coping strategies such as receiving help from family, friends, and social
services. Administrative data from a non-profit food distribution center,
electronic medical record (EMR) data from a safety-net healthcare system, and
publicly available residential appraisal data were linked to provide insight into
these coping strategies. Three broad types of coping strategies were examined:
changes in household structure, residential mobility, and utilization of social
services. Of 3,235 households, 20.2% had at least one adult member who
experienced a health shock. These households were more likely to gain additional
adult household members and employed household members, were more likely to move
residence and to move distances greater than one mile, and were less likely to
visit the food distribution center after the shock.
PMID- 28413219
TI - Contemporary biopsychosocial exercise prescription for chronic low back pain:
questioning core stability programs and considering context.
AB - This commentary explores the importance of considering the biopsychosocial model
and contextual factors when prescribing exercise. Diverse exercise programs for
patients with chronic low back pain (CLBP) produce similar outcomes, without one
specific exercise protocol demonstrating clear superiority. One clear barrier to
positive outcomes is poor exercise adherence. We suggest that there are certain
common contextual factors present in all exercise prescription scenarios that may
impact adherence and health-related outcomes. While challenging common core
stability exercise prescription, we present an argument for enhancing and
intentionally shaping the following contextual factors: the therapeutic alliance,
patient education, expectations and attributions of therapeutic success or
failure, and mastery or cognitive control over a problem. Overall, this
commentary argues that to improve exercise adherence and outcomes in the CLBP
population, the context in which exercise is delivered and the meaning patients
embody need to be considered and shaped by clinicians.
PMID- 28413220
TI - The physical and psychological impact of neurogenic claudication: the patients'
perspectives.
AB - BACKGROUND: The patient perspective regarding the impact of neurogenic
claudication (NC) has not been well studied. The objectives of this study were to
determine what is most bothersome among patients with NC and how it impacts their
lives and expectations with surgical and non-surgical treatment. METHODS: Semi
structured telephone interviews were conducted, audio recorded and transcribed
verbatim. A thematic analysis categorized key findings based on relative
importance and impact on participants. RESULTS: Twenty-eight individuals
participated in this study. Participants were most bothered by the pain of NC,
which dramatically impacted their lives. Inability to walk was the dominant
functional limitation and this impacted the ability to engage in recreational and
social activities. The most surprising finding was how frequently participants
reported significant emotional effects of NC. CONCLUSIONS: From a patients'
perspective NC has a significant multidimensional effects with pain, limited
walking ability and emotional effects being most impactful to their lives.
PMID- 28413221
TI - A proposed in vitro model for investigating the mechanisms of 'joint cracking': a
short report of preliminary techniques and observations.
AB - Joint "cracking" is common but not a clearly understood audible phenomenon. In
this brief report we propose an in-vitro model to potentially assist in revealing
a mechanism for, and therefore source of, this phenomenon. Using a suction cup
under tension and de-nucleated fluid to simulate synovial fluid, an audible
release with intra-articular cavity formation was elicited. This was followed by
a refractory period during which no audible crack could be elicited until the
observed cavity had slowly reabsorbed back into the joint fluid. Conversely, if
regular fluid containing pre-existing nuclei was used, a cavity formation
occurred but with neither an audible release nor subsequent refractory period.
With this simple in-vitro model, we were able to reproduce the characteristic
audible release, cavity formation and related refractory period typically
observed in related experiments in human joints. This simple in-vitro model may
be of use in helping to discern both the timing and precise nature of other yet
to be discerned mechanisms related to joint cracking.
PMID- 28413217
TI - Lymphotoxin signalling in tertiary lymphoid structures and immunotherapy.
AB - Tertiary lymphoid structures (TLS) often develop at sites of persistent
inflammation, including cancers and autoimmune diseases. In most cases, the
presence of TLS correlates with active immune responses. Because of their
proximity to pathological loci, TLS are an intriguing target for the manipulation
of immune responses. For several years, it has become clear that lymphotoxin (LT)
signalling plays critical roles in lymphoid tissue organogenesis and maintenance.
In the current review, we will discuss the role of LT signalling in the
development of TLS. With a focus on cancers and autoimmune diseases, we will
highlight the correlations between TLS and disease progression. We will also
discuss the current efforts and potential directions for manipulating TLS for
immunotherapies.
PMID- 28413222
TI - Calcium pyrophosphate deposition disease in the ankle joint: a case report.
AB - OBJECTIVE: To detail the presentation of calcium pyrophosphate deposition disease
(CPPD) in the ankle joint. The aim of this case report is to inform health-care
practitioners about the presentation of this condition in an uncommon location
and discuss the diagnosis, potential treatment, and management strategies for a
patient with CPPD. CLINICAL FEATURES: A 36-year-old male patient presented to a
chiropractic clinic with an acute, painful, and swollen ankle, which was later
diagnosed by plain film radiograph as CPPD. A rheumatology follow-up was
recommended and at-home treatment was prescribed to treat acute symptoms and
monitor progress. OUTCOME: No chiropractic treatment was provided and the patient
has been referred to a rheumatologist for further assessment. The diagnosis of
CPPD was confirmed and he was advised to take an anti-inflammatory if symptoms
recurred and booked for further follow-up in six months. SUMMARY: Although the
presentation is less common, CPPD can present in the ankle joint and mimic other
inflammatory disorders. Conservative treatment can be applied to treat acute
symptoms and referral to a rheumatologist is suggested to monitor progress of
this condition.
PMID- 28413223
TI - Chiropractic management of a geriatric patient with idiopathic neuralgic
amyotrophy: a case report.
AB - OBJECTIVE: The purpose of this paper is to describe chiropractic management of a
patient with neuralgic amyotrophy (NA) and to provide discussion regarding
presentation, differential diagnosis, management and prognosis of idiopathic NA.
CASE PRESENTATION: An 85 year old Caucasian male presented to a chiropractic
clinic with right periscapular and lateral rib cage pain. The patient had
previously sought evaluation and treatment from multiple health care providers
and underwent multiple interventions without relief. INTERVENTION AND OUTCOME:
The patient was managed with a course of chiropractic care and an ongoing home
exercise program was carried out. The patient reported spontaneous resolution of
pain approximately 14 months post onset. SUMMARY: NA is a poorly known clinical
entity amongst health care providers and poses challenges in timely and proper
diagnosis. Recognition of NA is important for patients to be best managed and for
more optimal patient outcomes to be achieved.
PMID- 28413225
TI - Pathological burst fracture in the cervical spine with negative red flags: a 12
year follow-up.
AB - In 2004, a 61-year-old male presented to a chiropractic clinic complaining of
neck pain after hearing a 'crunch' when getting out of bed that morning. The
initial history intake and physical examination identified no red flags or
indications for the patient's pain, with the exception of traction being pain
provoking. Conventional radiographs were ordered, which identified a pathological
burst fracture of the fourth cervical vertebra. This Imaging Case Review (ICR) is
to provide clinicians with a follow-up to the patient's care and current state.
PMID- 28413224
TI - Selecting and training opinion leaders and best practice collaborators:
experience from the Canadian Chiropractic Guideline Initiative.
AB - OBJECTIVES: To describe the process for selecting and training chiropractic
opinion leaders (OLs) and best practice collaborators (BPCs) to increase the
uptake of best practice. METHODS: In Phase 1, OLs were identified using a cross
sectional survey among Canadian chiropractic stakeholders. A 10-member committee
ranked nominees. Top-ranked nominees were invited to a training workshop. In
Phase 2, a national e-survey was administered to 7200 Canadian chiropractors to
identify additional OLs and BPCs. Recommended names were screened by OLs and
final selection made by consensus. Webinars were utilized to train BPCs to engage
peers in best practices, and facilitate guideline dissemination. RESULTS: In
Phase 1, 21 OLs were selected from 80 nominees. Sixteen attended a training
workshop. In Phase 2, 486 chiropractors recommended 1126 potential BPCs, of which
133 were invited to participate and 112 accepted. CONCLUSIONS: OLs and BPCs were
identified across Canada to enhance the uptake of research among chiropractors.
PMID- 28413226
TI - Grade V acromioclavicular joint separation in a 57-year-old mountain biker.
AB - Patients rarely present to a chiropractic office setting during the acute stage
of a high-grade (i.e. Rockwood types IV-VI) separation of the acromioclavicular
(AC) joint. Moreover, such cases are non-existent in the peer-reviewed
chiropractic literature. Some controversy exists over the optimal (surgical vs.
non-surgical) treatment of severe AC joint injuries. Published reports of
nonoperative management for grade V injuries of the AC joint are also scarce.
This case review highlights the plain film imaging and conservative management of
a 57-year-old patient diagnosed with an acute Rockwood type V AC joint
separation. Radiographs with nine years of follow-up are presented.
PMID- 28413227
TI - David C. Drum, DC, FCCS(C): an accomplished, multi-faceted individual.
AB - Pablo Picasso (1881-1973) is quoted as saying, "The meaning of life is to find
your gift. The purpose of life is to give it away." With these few words Picasso
captures the essence of David Drum's existence. From his birth in Moncton, NB,
through his formal education in Toronto, ON, to his so-called "retirement" in
Crystal Beach, ON, this paper spans 72 years, unveiling the broad range of
opportunities for growth David Drum has encountered in his life's journey and
documenting his acceptance of the obligations for proud philanthropy that
accompany them. Dr. Drum's many accomplishments, gifts, and contributions to the
profession and world of art are discussed.
PMID- 28413228
TI - Air Breathing Cathodes for Microbial Fuel Cell using Mn-, Fe-, Co- and Ni
containing Platinum Group Metal-free Catalysts.
AB - The oxygen reduction reaction (ORR) is one of the major factors that is limiting
the overall performance output of microbial fuel cells (MFC). In this study,
Platinum Group Metal-free (PGM-free) ORR catalysts based on Fe, Co, Ni, Mn and
the same precursor (Aminoantipyrine, AAPyr) were synthesized using identical
sacrificial support method (SSM). The catalysts were investigated for their
electrochemical performance, and then integrated into an air-breathing cathode to
be tested in "clean" environment and in a working microbial fuel cell (MFC).
Their performances were also compared to activated carbon (AC) based cathode
under similar conditions. Results showed that the addition of Mn, Fe, Co and Ni
to AAPyr increased the performances compared to AC. Fe-AAPyr showed the highest
open circuit potential (OCP) that was 0.307 +/- 0.001 V (vs. Ag/AgCl) and the
highest electrocatalytic activity at pH 7.5. On the contrary, AC had an OCP of
0.203 +/- 0.002 V (vs. Ag/AgCl) and had the lowest electrochemical activity. In
MFC, Fe-AAPyr also had the highest output of 251 +/- 2.3 MUWcm-2, followed by Co
AAPyr with 196 +/- 1.5 MUWcm-2, Ni-AAPyr with 171 +/- 3.6 MUWcm-2, Mn-AAPyr with
160 +/- 2.8 MUWcm-2 and AC 129 +/- 4.2 MUWcm-2. The best performing catalyst (Fe
AAPyr) was then tested in MFC with increasing solution conductivity from 12.4
mScm-1 to 63.1 mScm-1. A maximum power density of 482 +/- 5 MUWcm-2 was obtained
with increasing solution conductivity, which is one of the highest values
reported in the field.
PMID- 28413229
TI - Quality of maize for sale in markets in Benin and Niger.
AB - A follow-up study on the quality of maize for sale in West African public markets
was carried out in Benin and Niger from August 15-28, 2013. Complementing the
earlier study, this present assessment included not only retailers but also
wholesalers and maize producers. Samples were evaluated for parameters related to
the physical quality of the maize and for aflatoxin contamination. Most maize
value chain actors process their offered grain using traditional methods for
threshing, winnowing and drying. Maize for sale in the markets surveyed had an
average moisture content ranging between 12 and 14%. Non-grain impurities
amounted to 0-2.3% while mouldy grains ranged between 0.2 and 0.8%. The impurity
level in grain was three times higher among wholesalers compared to retailers and
producers. An insect pest, the Larger Grain Borer (Prostephanus truncatus (Horn)
was found only in Benin but Sitophilus zeamais Motschulsky, Cryptolestes
ferrugineus Stephens, and Tribolium castaneum Herbst, were present in maize for
sale in the markets in of both countries. Insect pest frequency was 16 times
higher in wholesalers' grain compared to that of retailers and producers.
Aflatoxin levels exceeding the accepted standard of 20 ppb were noted in markets
in both countries. The highest proportion of aflatoxin-contaminated maize was in
wholesalers' grain in Malanville market.
PMID- 28413230
TI - The relative effects of upwelling and river flow on the phytoplankton diversity
patterns in the ria of A Coruna (NW Spain).
AB - Phytoplankton species assemblages in estuaries are connected to those in rivers
and marine environments by local hydrodynamics leading to a continuous flow of
taxa. This study revealed differential effects of upwelling and river flow on
phytoplankton communities observed in 2011 along a salinity gradient from a river
reservoir connected to the sea through a ria-marine bay system in A Coruna (NW
Spain, 43 degrees 16-21' N, 8 degrees 16-22' W). With 130 phytoplankton taxa
identified, the assemblages were dominated in general by diatoms, particularly
abundant in the bay and in the estuary, but also by chlorophycea and
cyanobacteria in the reservoir. Considering the entire seasonal cycle, the local
assemblages were mainly characterized by changes in cryptophytes and diatoms,
small dinoflagellates and some freshwater chlorophycea. Salinity, nitrate, and
organic matter variables, were the main environmental factors related to the
changes in the phytoplankton communities through the system, while phosphate and
nitrite were also important for local communities in the estuary and the bay,
respectively. The corresponding local phytoplankton assemblages showed moderate
levels of connectivity. The estuarine community shared a variable number of taxa
with the adjacent zones, depending on the relative strength of upwelling (major
influence from the bay) and river flow (major influence of the reservoir) but had
on average 35% of unique taxa. Consequently, local and zonal diversity patterns
varied seasonally and were not simply related to the salinity gradient driven by
the river flow.
PMID- 28413231
TI - Development of a roof bolter canopy air curtain for respirable dust control.
AB - Testing of the roof bolter canopy air curtain (CAC) designed by the U.S. National
Institute for Occupational Safety and Health (NIOSH) has gone through many
iterations, demonstrating successful dust control performance under controlled
laboratory conditions. J.H. Fletcher & Co., an original equipment manufacturer of
mining equipment, further developed the concept by incorporating it into the
design of its roof bolting machines. In the present work, laboratory testing was
conducted, showing dust control efficiencies ranging from 17.2 to 24.5 percent.
Subsequent computational fluid dynamics (CFD) analysis revealed limitations in
the design, and a potential improvement was analyzed and recommended. As a
result, a new CAC design is being developed, incorporating the results of the
testing and CFD analysis.
PMID- 28413232
TI - The freshwater red alga Batrachospermum turfosum (Florideophyceae) can acclimate
to a wide range of light and temperature conditions.
AB - Batrachospermum turfosum Bory is one of the generalists among the few red algae
that have adapted to freshwater habitats, occurring in a variety of primarily
shaded, nutrient-poor micro-habitats with lotic (running) or lentic (standing)
waters. Seasonal variations in water level and canopy cover can expose this
sessile alga to widely fluctuating temperatures, solar irradiation and nutrient
availability. Here we report on the ecophysiology of B. turfosum collected from
an ultra-oligotrophic bog pool in the Austrian Alps. Photosynthesis as a function
of photon fluence density (PFD) and temperature was studied by measuring oxygen
evolution in combination with chlorophyll fluorescence. In addition, the effects
of ultraviolet radiation (UVR) on photosynthetic pigments were analysed using
HPLC and spectrophotometric methods, and cellular ultrastructure was studied
using transmission electron microscopy. We found that B. turfosum is adapted to
low light, with a light compensation point (Ic) and a light saturation point (Ik)
of 8.4 and 29.7 MUmol photons m- 2 s-1, respectively, but also tolerates higher
PFDs of ~1000 MUmol photons m-2 s-1, and is capable of net photosynthesis at
temperatures between 5 degrees C and 35 degrees C. Exposure to either UV-A or UV
AB for 102 h led to a strong transient drop in effective quantum yield
(DeltaF/FM'), followed by an acclimation to about 70% of initial DeltaF/FM'
values. Ultrastructural changes included the accumulation of plastoglobules and
dilated membranes after UVR treatment. Although all photosynthetic pigments
strongly decreased upon UVR exposure and no UV-photoprotectants (e.g. mycosporine
like amino acids) could be detected, the alga was capable of recovering
DeltaF/FM' and phycobiliproteins after UVR treatment. In summary, B. turfosum
tolerates a wide range of irradiation and temperature regimes, and these traits
may be the basis for its successful adaptation to challenging environments.
PMID- 28413233
TI - An alternative synthesis of Vandetanib (CaprelsaTM) via a microwave accelerated
Dimroth rearrangement.
AB - Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment
of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline,
using harsh reagents, in addition to requiring sequential protection and
deprotection steps. In the present work, use of the Dimroth rearrangement in the
key quinazoline forming step enabled the synthesis of Vandetanib in nine steps
(compared to the previously reported 12-14).
PMID- 28413234
TI - High-dimensional tests for functional networks of brain anatomic regions.
AB - Exploring resting-state brain functional connectivity of autism spectrum
disorders (ASD) using functional magnetic resonance imaging (fMRI) data has
become a popular topic over the past few years. The data in a standard brain
template consist of over 170,000 voxel specific points in time for each human
subject. Such an ultra-high dimensionality makes the voxel-level functional
connectivity analysis (involving four billion voxel pairs) both statistically and
computationally inefficient. In this work, we introduce a new framework to
identify the functional brain network at the anatomical region level for each
individual. We propose two pairwise tests to detect region dependence, and one
multiple testing procedure to identify global structures of the network. The
limiting null distribution of each test statistic is derived. It is also shown
that the tests are rate optimal when the alternative block networks are sparse.
The numerical studies show that the proposed tests are valid and powerful. We
apply our method to a resting-state fMRI study on autism and identify patient
unique and control-unique hub regions. These findings are biologically meaningful
and consistent with the existing literature.
PMID- 28413235
TI - Comparison of total and aqua regia extractability of heavy metals in sewage
sludge: The case study of a certified reference material.
AB - A number of different digestion methods, including aqua regia extraction
following two ISO guides were used in an inter-laboratory comparison study. The
results obtained showed comparable values for the total and aqua regia
extractable content of As, Cu, Fe, Hg, Pb and Zn, while Cd, Co and Cr results
were about 10% lower when aqua regia was employed. This small difference was
covered by the between-laboratory relative standard deviation of the
measurements; therefore in this study no difference in the extraction of the
elements by the employed methods was found. The high organic matter content,
together with low SiO2 and refractory aluminium and iron oxide amount as well as
the small particle size of the sewage sludge material was reputed to have an
effect on the extracting capacity of a weaker solvent such as aqua regia,
bringing its results close to the total content ones.
PMID- 28413237
TI - In Space and Time: Territorial Animals are Attracted to Conspecific Chemical
Cues.
AB - Territorial animals lay scent marks around their territories to broadcast their
presence, but these olfactory signals can both attract and repel con-specifics.
Attraction or aversion can have a profound impact in terms of space use and
thereby influence an individual's access to resources and mates. Here, we test
the impact of chemical signals on the long-term space use and activity of
receivers, comparing the response of males and females, territory holders, and
temporary visitors in Sceloporus undulatus lizards in the field. We placed either
male femoral gland secretions (chemical) or blank (control) cues on resident male
landmarks, repeatedly over 5 d, while monitoring the activity and location of all
lizards in the vicinity. We found that resident males and females, but not non
resident males, were active on more days near landmarks treated with chemical
cues than landmarks treated with control cues. Non-resident males remained closer
to chemical than control cues. These results suggest that territorial scent marks
are attractive to conspecifics and impact space use, but that the specific
effects depend on receiver sex and residency status. Such subtle or gradual
changes in behavior may frequently be overlooked by short-term choice
experiments. Future studies investigating the behavioral significance of a
communicative signal should consider these finer details of behavior for a more
comprehensive assessment.
PMID- 28413236
TI - Scopulariopsis and scopulariopsis-like species from indoor environments.
AB - Scopulariopsis-like species are often reported from the indoor environment, as
well as from clinical samples. The lack of type isolates and thorough
phylogenetic studies in the Microascaceae hampered the correct identification of
these isolates. Based on recent phylogenetic studies, which resulted in multiple
name changes, the aim is to molecularly identify the Scopulariopsis and
scopulariopsis-like species which occur in the indoor environment and give an
overview of the current species in these genera and their habitats. Strains from
the CBS culture collection were supplemented with almost 80 indoor strains of
which the internal transcribed spacer 1 and 2 and intervening 5.8S nrDNA (ITS),
beta-tubulin (tub2) and translation elongation factor 1-alpha (tef1) gene regions
were sequenced for phylogenetic inference. The multi-gene phylogenies recognise
33 Microascus species and 12 Scopulariopsis species and showed that the recently
established genus Fuscoannellis, typified by Scopulariopsis carbonaria, should be
synonymized with the genus Yunnania. Seven new Microascus species, four new
Scopulariopsis species, and one new Yunnania species, are described, and a new
name in Microascus and two new name combinations (one in Microascus, and one in
Yunnania) are proposed. In the indoor environment 14 Microascus species and three
Scopulariopsis species were found. Scopulariopsis brevicaulis (22 indoor
isolates) and Microascus melanosporus (19 indoor isolates) are the most common
indoor species, in number of isolates, followed by M. paisii (8 indoor isolates)
and S. candida (7 indoor isolates). A genus phylogeny based on the ITS, tef1 and
the large subunit 28S nrDNA (LSU) of the type or representative isolates of all
here recognised species is provided depicting all species habitats. No
correlation between phylogenetic relationship and habitat preference could be
observed. Ten species which are found indoor are also found in relation with
human-derived samples. A table showing recent name changes and a key to common
species of Scopulariopsis and scopulariopsis-like genera found indoors is
included.
PMID- 28413238
TI - Formation of Gold(III) Alkyls from Gold Alkoxide Complexes.
AB - The gold(III) methoxide complex (C?N?C)AuOMe (1) reacts with tris(p
tolyl)phosphine in benzene at room temperature under O abstraction to give the
methylgold product (C?N?C)AuMe (2) together with O=P(p-tol)3 ((C?N?C) = [2,6
(C6H3t Bu-4)2pyridine]2-). Calculations show that this reaction is energetically
favorable (DeltaG = -32.3 kcal mol-1). The side products in this reaction, the
Au(II) complex [Au(C?N?C)]2 (3) and the phosphorane (p-tol)3P(OMe)2, suggest that
at least two reaction pathways may operate, including one involving (C?N?C)Au*
radicals. Attempts to model the reaction by DFT methods showed that PPh3 can
approach 1 to give a near-linear Au-O-P arrangement, without phosphine
coordination to gold. The analogous reaction of (C?N?C)AuOEt, on the other hand,
gives exclusively a mixture of 3 and (p-tol)3P(OEt)2. Whereas the reaction of
(C?N?C)AuOR (R = But, p-C6H4F) with P(p-tol)3 proceeds over a period of hours,
compounds with R = CH2CF3, CH(CF3)2 react almost instantaneously, to give 3 and
O=P(p-tol)3. In chlorinated solvents, treatment of the alkoxides (C?N?C)AuOR with
phosphines generates [(C?N?C)Au(PR3)]Cl, via Cl abstraction from the solvent.
Attempts to extend the synthesis of gold(III) alkoxides to allyl alcohols were
unsuccessful; the reaction of (C?N?C)AuOH with an excess of CH2=CHCH2OH in
toluene led instead to allyl alcohol isomerization to give a mixture of gold
alkyls, (C?N?C)AuR' (R' = -CH2CH2CHO (10), -CH2CH(CH2OH)OCH2CH=CH2 (11)), while 2
methallyl alcohol affords R' = CH2CH(Me)CHO (12). The crystal structure of 11 was
determined. The formation of Au-C instead of the expected Au-O products is in
line with the trend in metal-ligand bond dissociation energies for Au(III): M-H >
M-C > M-O.
PMID- 28413239
TI - Tuning the Si-N Interaction in Metalated Oligosilanylsilatranes.
AB - Most known silatrane chemistry is concerned with examples where the attached
silatrane substituent atom is that of an element more electronegative than
silicon. The current study features silylated silatranes with a range of
electropositive elements attached to the silyl group. The resulting compounds
show different degrees of electron density on the silatrane-substituted silicon
atom. This directly affects the Si-N interaction of the silatrane which can be
monitored either by 29Si NMR spectroscopy or directly by single crystal XRD
analysis of the Si-N distance. Within the sample of study the Si-N distance is
increased from 2.153 to 3.13 A. Moreover, the bis(trimethylsilyl)silatranylsilyl
unit was studied as a substituent for disilylated germylene adducts.
PMID- 28413240
TI - Detection of increased vasa vasorum in artery walls: Improving CT number accuracy
using image deconvolution.
AB - Changes in arterial wall perfusion are an indicator of early atherosclerosis.
This is characterized by an increased spatial density of vasa vasorum (VV), the
micro-vessels that supply oxygen and nutrients to the arterial wall. Detection of
increased VV during contrast-enhanced computed tomography (CT) imaging is limited
due to contamination from blooming effect from the contrast-enhanced lumen. We
report the application of an image deconvolution technique using a measured
system point-spread function, on CT data obtained from a photon-counting CT
system to reduce blooming and to improve the CT number accuracy of arterial wall,
which enhances detection of increased VV. A phantom study was performed to assess
the accuracy of the deconvolution technique. A porcine model was created with
enhanced VV in one carotid artery; the other carotid artery served as a control.
CT images at an energy range of 25-120 keV were reconstructed. CT numbers were
measured for multiple locations in the carotid walls and for multiple time
points, pre and post contrast injection. The mean CT number in the carotid wall
was compared between the left (increased VV) and right (control) carotid
arteries. Prior to deconvolution, results showed similar mean CT numbers in the
left and right carotid wall due to the contamination from blooming effect,
limiting the detection of increased VV in the left carotid artery. After
deconvolution, the mean CT number difference between the left and right carotid
arteries was substantially increased at all the time points, enabling detection
of the increased VV in the artery wall.
PMID- 28413241
TI - Development of Portable Aerosol Mobility Spectrometer for Personal and Mobile
Aerosol Measurement.
AB - We describe development of a Portable Aerosol Mobility Spectrometer (PAMS) for
size distribution measurement of submicrometer aerosol. The spectrometer is
designed for use in personal or mobile aerosol characterization studies and
measures approximately 22.5 * 22.5 * 15 cm and weighs about 4.5 kg including the
battery. PAMS uses electrical mobility technique to measure number-weighted
particle size distribution of aerosol in the 10-855 nm range. Aerosol particles
are electrically charged using a dual-corona bipolar corona charger, followed by
classification in a cylindrical miniature differential mobility analyzer. A
condensation particle counter is used to detect and count particles. The mobility
classifier was operated at an aerosol flow rate of 0.05 L/min, and at two
different user-selectable sheath flows of 0.2 L/min (for wider size range 15-855
nm) and 0.4 L/min (for higher size resolution over the size range of 10.6-436
nm). The instrument was operated in voltage stepping mode to retrieve the size
distribution, which took approximately 1-2 minutes, depending on the
configuration. Sizing accuracy and resolution were probed and found to be within
the 25% limit of NIOSH criterion for direct-reading instruments (NIOSH 2012).
Comparison of size distribution measurements from PAMS and other commercial
mobility spectrometers showed good agreement. The instrument offers unique
measurement capability for on-person or mobile size distribution measurements of
ultrafine and nanoparticle aerosol.
PMID- 28413242
TI - Agriculture in Africa - Telling myths from facts: A synthesis.
AB - Stylized facts drive research agendas and policy debates. Yet robust stylized
facts are hard to come by, and when available, often outdated. The 12 papers in
this Special Issue revisit conventional wisdom on African agriculture and its
farmers' livelihoods using nationally representative surveys from the Living
Standards Measurement Study-Integrated Surveys on Agriculture Initiative in six
African countries. At times they simply confirm our common understanding of the
topic. But they also throw up a number of surprises, redirecting policy debates
while fine-tuning others. Overall, the project calls for more attention to
checking and updating our common wisdom. This requires nationally representative
data, and sufficient incentives among researchers and policymakers alike. Without
well-grounded stylized facts, they can easily be profoundly misguided.
PMID- 28413243
TI - Ten striking facts about agricultural input use in Sub-Saharan Africa.
AB - Conventional wisdom holds that Sub-Saharan African farmers use few modern inputs
despite the fact that most poverty-reducing agricultural growth in the region is
expected to come largely from expanded use of inputs that embody improved
technologies, particularly improved seed, fertilizers and other agro-chemicals,
machinery, and irrigation. Yet following several years of high food prices,
concerted policy efforts to intensify fertilizer and hybrid seed use, and
increased public and private investment in agriculture, how low is modern input
use in Africa really? This article revisits Africa's agricultural input
landscape, exploiting the unique, recently collected, nationally representative,
agriculturally intensive, and cross-country comparable Living Standard
Measurement Study-Integrated Surveys on Agriculture (LSMS-ISA) covering six
countries in the region (Ethiopia, Malawi, Niger, Nigeria, Tanzania, and Uganda).
Using data from over 22,000 households and 62,000 agricultural plots, we offer
ten potentially surprising facts about modern input use in Africa today.
PMID- 28413244
TI - Agricultural intensification: The status in six African countries.
AB - Boserup and Ruthenberg (BR) provided the framework to analyze the impact of
population growth and market access on the intensification of farming systems.
Prior evidence in Africa is consistent with the framework. Over the past two
decades, rapid population growth has put farming systems under stress, while
rapid urbanization and economic growth have provided new market opportunities.
New measures of agro-ecological potential and urban gravity are developed to
analyze their impact on population density and market access. The descriptive and
regression analyses show that the patterns of intensification across countries
are only partially consistent with the BR predictions. Fallow areas have
disappeared, but cropping intensities remain very low. The use of organic and
chemical fertilizers is too low to maintain soil fertility. Investments in
irrigation are inadequate. In light of the promising outcomes suggested by the
Boserup-Ruthenberg framework, the process of intensification across these
countries appears to have been weak.
PMID- 28413245
TI - Is increasing inorganic fertilizer use for maize production in SSA a profitable
proposition? Evidence from Nigeria.
AB - Inorganic fertilizer use across Sub-Saharan Africa is generally considered to be
low. Yet, the notion that fertilizer use is too low is predicated on the
assumption that it is profitable to use rates higher than currently observed.
There is, however, limited empirical evidence to support this. Using a nationally
representative panel dataset, this paper empirically estimates the profitability
of fertilizer use for maize production in Nigeria. We find that fertilizer use in
Nigeria is not as low as conventional wisdom suggests. Low marginal physical
product and high transportation costs significantly reduce the profitability of
fertilizer use. Apart from reduced transportation costs, other constraints such
as soil quality, timely access to the product, and availability of complementary
inputs such as improved seeds, irrigation and credit, as well as good management
practices are also necessary for sustained agricultural productivity
improvements.
PMID- 28413246
TI - How much of the labor in African agriculture is provided by women?
AB - The contribution of women to labor in African agriculture is regularly quoted in
the range of 60-80%. Using individual, plot-level labor input data from
nationally representative household surveys across six Sub-Saharan African
countries, this study estimates the average female labor share in crop production
at 40%. It is slightly above 50% in Malawi, Tanzania, and Uganda, and
substantially lower in Nigeria (37%), Ethiopia (29%), and Niger (24%). There are
no systematic differences across crops and activities, but female labor shares
tend to be higher in households where women own a larger share of the land and
when they are more educated. Controlling for the gender and knowledge profile of
the respondents does not meaningfully change the predicted female labor shares.
The findings question prevailing assertions regarding substantial gains in
aggregate crop output as a result of increasing female agricultural productivity.
PMID- 28413247
TI - Agricultural factor markets in Sub-Saharan Africa: An updated view with formal
tests for market failure.
AB - This paper uses the recently collected Living Standard Measurement Study
Integrated Surveys on Agriculture Initiative data sets from five countries in Sub
Saharan Africa to provide a comprehensive overview of factor market participation
by agrarian households and to formally test for failures in rural markets. Under
complete and competitive markets, households can solve their consumption and
production problems separately, so that household factor endowments do not
predict input demand. This paper implements a simple, theoretically grounded test
of this separation hypothesis, which can be interpreted as a reduced form test of
market failure. In all five study countries, the analysis finds strong evidence
of factor market failure. Moreover, those failures appear general and structural,
not specific to subpopulations defined by gender, geography, human capital, or
land quality. However, we show that rural markets are not generally missing in an
absolute sense, suggesting that market existence is less of a problem than market
function.
PMID- 28413248
TI - Smallholders' land access in Sub-Saharan Africa: A new landscape?
AB - While scholars long recognized the importance of land markets as a key driver of
rural non-farm development and transformation in rural areas, evidence on the
extent of their operation and the nature of participants remains limited. We use
household data from 6 countries to show that there is great potential for such
markets to increase productivity and equalize factor ratios. While rental markets
transfer land to land-poor and labor-rich producers, their operation and thus
impact may be constrained by policy restrictions. Their functioning may also be
constrained by ill-defined or insecure rights that may arise from failure to
fully compensate existing rights in cases of expropriation, a failure to
implement more broadly land policies or to do so in a gender sensitive manner.
Methodological and substantive conclusions are derived.
PMID- 28413249
TI - Agricultural input credit in Sub-Saharan Africa: Telling myth from facts.
AB - Recent evidence shows that many Sub-Saharan African farmers use modern inputs,
but there is limited information on how these inputs are financed. We use recent
nationally representative data from four countries to explore input financing and
the role of credit therein. A number of our results contradict "conventional
wisdom" found in the literature. Our results consistently show that traditional
credit use, formal or informal, is extremely low (across credit type, country,
crop and farm size categories). Instead, farmers primarily finance modern input
purchases with cash from nonfarm activities and crop sales. Tied output-labor
arrangements (which have received little empirical treatment in the literature)
appear to be the only form of credit relatively widely used for farming.
PMID- 28413250
TI - Agricultural commercialization and nutrition revisited: Empirical evidence from
three African countries.
AB - The transition from subsistence to commercial agriculture is key for economic
growth. But what are the consequences for nutritional outcomes? The evidence to
date has been scant and inconclusive. This study contributes to the debate by
revisiting two prevailing wisdoms: (a) market participation by African
smallholders remains low; and (b) the impact of commercialization on nutritional
outcomes is generally positive. Using nationally representative data from three
African countries, the analysis reveals high levels of commercialization by even
the poorest and smallest landholders, with rates of market participation as high
as 90%. Female farmers participate less, but tend to sell larger shares of their
production, conditional on participation. Second, we find little evidence of a
positive relationship between commercialization and nutritional status. As
countries and international agencies prioritize the importance of nutrition
sensitive agriculture, better understanding of the transmission channels between
crop choices and nutritional outcomes should remain a research priority.
PMID- 28413251
TI - Food price seasonality in Africa: Measurement and extent.
AB - Everyone knows about seasonality. But what exactly do we know? This study
systematically measures seasonal price gaps at 193 markets for 13 food
commodities in seven African countries. It shows that the commonly used dummy
variable or moving average deviation methods to estimate the seasonal gap can
yield substantial upward bias. This can be partially circumvented using
trigonometric and sawtooth models, which are more parsimonious. Among staple
crops, seasonality is highest for maize (33 percent on average) and lowest for
rice (161/2 percent). This is two and a half to three times larger than in the
international reference markets. Seasonality varies substantially across market
places but maize is the only crop in which there are important systematic country
effects. Malawi, where maize is the main staple, emerges as exhibiting the most
acute seasonal differences. Reaching the Sustainable Development Goal of Zero
Hunger requires renewed policy attention to seasonality in food prices and
consumption.
PMID- 28413252
TI - Labor productivity and employment gaps in Sub-Saharan Africa.
AB - Drawing on a new set of nationally representative, internationally comparable
household surveys, this paper provides an overview of key features of structural
transformation - labor allocation and labor productivity - in four African
economies. New, micro-based measures of sector labor allocation and cross-sector
productivity differentials describe the incentives households face when
allocating their labor. These measures are similar to national accounts-based
measures that are typically used to characterize structural change. However,
because agricultural workers supply far fewer hours of labor per year than do
workers in other sectors in all of the countries analyzed, productivity gaps
shrink by half, on average, when expressed on a per-hour basis. Underlying the
productivity gaps that are prominently reflected in national accounts data are
large employment gaps, which call into question the productivity gains that
laborers can achieve through structural transformation. Furthermore,
agriculture's continued relevance to structural change in Sub-Saharan Africa is
highlighted by the strong linkages observed between rural non-farm activities and
primary agricultural production.
PMID- 28413253
TI - Are African households (not) leaving agriculture? Patterns of households' income
sources in rural Sub-Saharan Africa.
AB - This paper uses comparable income aggregates from 41 national household surveys
from 22 countries to explore the patterns of income generation among rural
households in Sub-Saharan Africa, and to compare household income strategies in
Sub-Saharan Africa with those in other regions. The paper seeks to understand how
geography drives these strategies, focusing on the role of agricultural potential
and distance to urban areas. Specialization in on-farm activities continues to be
the norm in rural Africa, practiced by 52 percent of households (as opposed to 21
percent of households in other regions). Regardless of distance and integration
in the urban context, when agro-climatic conditions are favorable, farming
remains the occupation of choice for most households in the African countries for
which the study has geographically explicit information. However, the paper finds
no evidence that African households are on a different trajectory than households
in other regions in terms of transitioning to non-agricultural based income
strategies.
PMID- 28413254
TI - Non-farm entrepreneurship in rural sub-Saharan Africa: New empirical evidence.
AB - We report on the prevalence and patterns of non-farm enterprises in six sub
Saharan African countries, and study their performance in terms of labor
productivity, survival and exit, using the World Bank's Living Standards
Measurement Study - Integrated Surveys on Agriculture (LSMS-ISA). Rural
households operate enterprises due to both push and pull factors and tend to do
so predominantly in easy-to-enter activities, such as sales and trade, rather
than in activities that require higher starting costs, such as transport
services, or educational investment, such as professional services. Labor
productivity differs widely: rural and female-headed enterprises, those located
further away from population centers, and businesses that operate intermittently
have lower levels of labor productivity compared to urban and male-owned
enterprises, or enterprises that operate throughout the year. Finally, rural
enterprises exit the market primarily due to a lack of profitability or finance,
and due to idiosyncratic shocks.
PMID- 28413255
TI - Scalar and vector self-energies of heavy baryons in nuclear medium.
AB - The in-medium sum rules are employed to calculate the shifts in the mass and
residue as well as the scalar and vector self-energies of the heavy [Formula: see
text] and [Formula: see text] baryons, with Q being b or c quark. The maximum
shift in mass due to nuclear matter belongs to the [Formula: see text] baryon and
it is found to be [Formula: see text]. In the case of residue, it is obtained
that the residue of [Formula: see text] baryon is maximally affected by the
nuclear medium with the shift [Formula: see text]. The scalar and vector self
energies are found to be [Formula: see text], [Formula: see text], [Formula: see
text], [Formula: see text], [Formula: see text], [Formula: see text] and
[Formula: see text], [Formula: see text], [Formula: see text], [Formula: see
text], [Formula: see text] and [Formula: see text].
PMID- 28413256
TI - Dynamics of Postcombustion CO2 Capture Plants: Modeling, Validation, and Case
Study.
AB - The capture of CO2 from power plant flue gases provides an opportunity to
mitigate emissions that are harmful to the global climate. While the process of
CO2 capture using an aqueous amine solution is well-known from experience in
other technical sectors (e.g., acid gas removal in the gas processing industry),
its operation combined with a power plant still needs investigation because in
this case, the interaction with power plants that are increasingly operated
dynamically poses control challenges. This article presents the dynamic modeling
of CO2 capture plants followed by a detailed validation using transient
measurements recorded from the pilot plant operated at the Maasvlakte power
station in the Netherlands. The model predictions are in good agreement with the
experimental data related to the transient changes of the main process variables
such as flow rate, CO2 concentrations, temperatures, and solvent loading. The
validated model was used to study the effects of fast power plant transients on
the capture plant operation. A relevant result of this work is that an integrated
CO2 capture plant might enable more dynamic operation of retrofitted fossil fuel
power plants because the large amount of steam needed by the capture process can
be diverted rapidly to and from the power plant.
PMID- 28413257
TI - Tuning and Locking the Localized Surface Plasmon Resonances of CuS (Covellite)
Nanocrystals by an Amorphous CuPd x S Shell.
AB - We demonstrate the stabilization of the localized surface plasmon resonance
(LSPR) in a semiconductor-based core-shell heterostructure made of a plasmonic
CuS core embedded in an amorphous-like alloyed CuPd x S shell. This
heterostructure is prepared by reacting the as-synthesized CuS nanocrystals (NCs)
with Pd2+ cations at room temperature in the presence of an electron donor
(ascorbic acid). The reaction starts from the surface of the CuS NCs and proceeds
toward the center, causing reorganization of the initial lattice and
amorphization of the covellite structure. According to density functional
calculations, Pd atoms are preferentially accommodated between the bilayer formed
by the S-S covalent bonds, which are therefore broken, and this can be understood
as the first step leading to amorphization of the particles upon insertion of the
Pd2+ ions. The position and intensity in near-infrared LSPRs can be tuned by
altering the thickness of the shell and are in agreement with the theoretical
optical simulation based on the Mie-Gans theory and Drude model. Compared to the
starting CuS NCs, the amorphous CuPd x S shell in the core-shell nanoparticles
makes their plasmonic response less sensitive to a harsh oxidation environment
(generated, for example, by the presence of I2).
PMID- 28413258
TI - Fluorinated polyurethane scaffolds for 19F magnetic resonance imaging.
AB - Polymers are increasingly employed in implant materials. To reduce the incidence
of complications, which in the case of vascular grafts include incorrect
placement and restenosis, materials are needed which allow for image-guided
implantation, as well as for accurate and efficient postoperative implant
imaging. We here describe amorphous fluorinated polymers based on thermoplastic
polyurethane (19F-TPU), and show that are useful starting materials for
developing tissue-engineered vascular grafts which can be detected using 19F MRI.
PMID- 28413259
TI - Materials Genome in Action: Identifying the Performance Limits of Physical
Hydrogen Storage.
AB - The Materials Genome is in action: the molecular codes for millions of materials
have been sequenced, predictive models have been developed, and now the challenge
of hydrogen storage is targeted. Renewably generated hydrogen is an attractive
transportation fuel with zero carbon emissions, but its storage remains a
significant challenge. Nanoporous adsorbents have shown promising physical
adsorption of hydrogen approaching targeted capacities, but the scope of studies
has remained limited. Here the Nanoporous Materials Genome, containing over 850
000 materials, is analyzed with a variety of computational tools to explore the
limits of hydrogen storage. Optimal features that maximize net capacity at room
temperature include pore sizes of around 6 A and void fractions of 0.1, while at
cryogenic temperatures pore sizes of 10 A and void fractions of 0.5 are optimal.
Our top candidates are found to be commercially attractive as "cryo-adsorbents",
with promising storage capacities at 77 K and 100 bar with 30% enhancement to 40
g/L, a promising alternative to liquefaction at 20 K and compression at 700 bar.
PMID- 28413260
TI - Missing Linkers: An Alternative Pathway to UiO-66 Electronic Structure
Engineering.
AB - UiO-66 is a promising metal-organic framework for photocatalytic applications.
However, the ligand-to-metal charge transfer of an excited electron is
inefficient in the pristine material. Herein, we assess the influence of missing
linker defects on the electronic structure of UiO-66 and discuss their ability to
improve ligand-to-metal charge transfer. Using a new defect classification
system, which is transparent and easily extendable, we identify the most
promising photocatalysts by considering both relative stability and electronic
structure. We find that the properties of UiO-66 defect structures largely depend
on the coordination of the constituent nodes and that the nodes with the
strongest local distortions alter the electronic structure most. Defects hence
provide an alternative pathway to tune UiO-66 for photocatalytic purposes,
besides linker modification and node metal substitution. In addition, the
decomposition of MOF properties into node- and linker-based behavior is more
generally valid, so we propose orthogonal electronic structure tuning as a
paradigm in MOF design.
PMID- 28413261
TI - Sculpting Silica Colloids by Etching Particles with Nonuniform Compositions.
AB - We present the synthesis of new shapes of colloidal silica particles by
manipulating their chemical composition and subsequent etching. Segments of
silica rods, prepared by the ammonia catalyzed hydrolysis and condensation of
tetraethylorthosilicate (TEOS) from polyvinylpyrrolidone loaded water droplets,
were grown under different conditions. Upon decreasing temperature, delaying
ethanol addition, or increasing monomer concentration, the rate of dissolution of
the silica segment subsequently formed decreased. A watery solution of NaOH (~mM)
selectively etched these segments. Further tuning the conditions resulted in rod
cone or cone-cone shapes. Deliberately modulating the composition along the
particle's length by delayed addition of (3-aminopropyl)-triethoxysilane (APTES)
also allowed us to change the composition stepwise. The faster etching of this
coupling agent in neutral conditions or HF afforded an even larger variety of
particle morphologies while in addition changing the chemical functionality. A
comparable step in composition was applied to silica spheres. Biamine functional
groups used in a similar way as APTES caused a charge inversion during the
growth, causing dumbbells and higher order aggregates to form. These particles
etched more slowly at the neck, resulting in a biconcave silica ring sandwiched
between two silica spheres, which could be separated by specifically etching the
functionalized layer using HF.
PMID- 28413263
TI - Intensified Microwave-Assisted N-Acylation Procedure - Synthesis and Activity
Evaluation of TRPC3 Channel Agonists with a 1,3-Dihydro-2H-benzo[d]imidazol-2-one
Core.
AB - Upon controlled microwave heating and using cyanuric chloride as a coupling
reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H
benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed.
Compared to the few conventional protocols, a drastic reduction in processing
time from ca. 2 days down to 10 minutes was achieved accompanied by significantly
improved product yields. The robustness of the method was confirmed by 18
additional examples including aromatic, aliphatic, and heterocyclic amines and
acids. The obtained agonists were screened for biological activity at 1 MUM
concentration and few structure-activity relations have been established.
PMID- 28413264
TI - Climate Variability and Inter-Provincial Migration in South America, 1970-2011.
AB - We examine the effect of climate variability on human migration in South America.
Our analyses draw on over 21 million observations of adults aged 15-40 from 25
censuses conducted in eight South American countries. Addressing limitations
associated with methodological diversity among prior studies, we apply a common
analytic approach and uniform definitions of migration and climate across all
countries. We estimate the effects of climate variability on migration overall
and also investigate heterogeneity across sex, age, and socioeconomic groups,
across countries, and across historical climate conditions. We also disaggregate
migration by the rural/urban status of destination. We find that exposure to
monthly temperature shocks has the most consistent effects on migration relative
to monthly rainfall shocks and gradual changes in climate over multi-year
periods. We also find evidence of heterogeneity across demographic groups and
countries. Analyses that disaggregate migration by the rural/urban status of
destination suggest that much of the climate-related inter-province migration is
directed toward urban areas. Overall, our results underscore the complexity of
environment-migration linkages and challenge simplistic narratives that envision
a linear and monolithic migratory response to changing climates.
PMID- 28413265
TI - Zinc toxicity stimulates microbial production of extracellular polymers in a
copiotrophic acid soil.
AB - The production of extracellular polymeric substances (EPS) is crucial for biofilm
structure, microbial nutrition and proximal stability of habitat in a variety of
environments. However, the production patterns of microbial EPS in soils as
affected by heavy metal contamination remain uncertain. Here we investigate the
extracellular response of the native microbial biomass in a grassland soil
treated with refined glycerol or crude unrefined biodiesel co-product (BCP) with
and without ZnCl2. We extracted microbial EPS and more readily soluble microbial
products (SMP), and quantified total polysaccharide, uronic acid, and protein
content in these respective extracts. Organic addition, especially BCP,
significantly stimulated the production of EPS-polysaccharide and protein but had
no impact on EPS-uronic acids, while in the SMP-fraction, polysaccharides and
uronic acids were both significantly increased. In response to the inclusion of
Zn2+, both EPS- and SMP-polysaccharides increased. This implies firstly that a
tolerance mechanism of soil microorganisms against Zn2+ toxicity exists through
the stimulation of SMP and EPS production, and secondly that co-products of
biofuel industries may have value-added use in bioremediation efforts to support
in-situ production of microbial biopolymers. Microbial films and mobile polymers
are likely to impact a range of soil properties. The recent focus on EPS research
in soils is anticipated to help contribute an improved understanding of biofilm
dynamics in other complex systems - such as continuously operated bioreactors.
PMID- 28413262
TI - Polymeric Materials for Gene Delivery and DNA Vaccination.
AB - Gene delivery holds great potential for the treatment of many different diseases.
Vaccination with DNA holds particular promise, and may provide a solution to many
technical challenges that hinder traditional vaccine systems including rapid
development and production and induction of robust cell-mediated immune
responses. However, few candidate DNA vaccines have progressed past preclinical
development and none have been approved for human use. This Review focuses on the
recent progress and challenges facing materials design for nonviral DNA vaccine
drug delivery systems. In particular, we highlight work on new polymeric
materials and their effects on protective immune activation, gene delivery, and
current efforts to optimize polymeric delivery systems for DNA vaccination.
PMID- 28413266
TI - Not just a separate consent for anesthesia!
PMID- 28413267
TI - Vasopressors: Do they have any role in hemorrhagic shock?
AB - The priority in the management of patients with traumatic hemorrhagic shock is to
control the bleeding with simultaneous volume resuscitation to maintain adequate
tissue perfusion. Fluid replacement remains the mainstay of initial resuscitation
in hemorrhagic shock. Traditionally, vasopressors are contraindicated in the
early management of hemorrhagic shock due to their deleterious consequences,
although vasopressors may have a role in resuscitation when vasoplegic shock
ensues and blood pressure cannot be maintained by fluids alone. Use of
vasopressors is not recommended according to the Advanced Trauma Life SupportR
management principles. The role of vasopressors remains controversial with no
clear guidelines on the timing, type, and dose of these drugs in hemorrhagic
shock. Among vasopressors, norepinephrine and vasopressin have been used in the
majority of the trials, although not many studies compare the effect of these two
on long-term survival in trauma patients. This article reviews the
pathophysiology of hemorrhagic shock, adverse effects of fluid resuscitation, and
the various experimental and clinical studies on the use of vasopressors in the
early phase of resuscitation in hemorrhagic shock.
PMID- 28413268
TI - Novel propofol derivatives and implications for anesthesia practice.
AB - Propofol (2,6-diisopropylphenol) is the most commonly used intravenous agent for
induction of anesthesia. It is also used for maintenance of anesthesia and
sedation in both Intensive Care Units and outpatient procedural settings. Its
success in the clinical setting has been a result of its rapid onset, short
duration of action, and minimal side effects despite disadvantages associated
with its oil emulsion formulation. Early attempts to alter the standard emulsion
or to develop new formulations with cyclodextrins and micelles to resolve issues
with pain upon injection, the need for antimicrobial agents, and possible
hyperlipidemia have mostly failed. With these challenges in the foreground,
attention has now shifted to the use of more prodrugs and exogenous alternatives,
the success of which is yet to be determined. These new agents must offer
significant clinical advantages over the well-entrenched, generic propofol oil
emulsion to justify higher costs and to be well received in the increasingly cost
conscious healthcare marketplace.
PMID- 28413270
TI - The effect of perioperative esmolol on early postoperative pain: A systematic
review and meta-analysis.
AB - Esmolol has been shown to improve postoperative pain and reduce opioid
requirements. The aim of this systematic review was to evaluate the effect of
perioperative esmolol as an adjunct on early postoperative pain intensity,
recovery profile, and anesthetic requirement. Databases were searched for
randomized placebo-controlled trials evaluating the effects of esmolol during
general anesthesia. Primary outcomes were related to early postoperative pain
whereas secondary outcomes were related to emergence time, postoperative nausea
and vomiting, and intraoperative anesthetic requirement. Nineteen trials were
identified involving 936 patients (esmolol = 470, placebo = 466). In esmolol
group, numeric pain scores at rest in the immediate postoperative period were
reduced by 1.16 (95% confidence interval [CI]: 1.97-0.35, I2 = 96.7%) out of 10.
Opioid consumption was also decreased in the postanesthesia care unit compared
with placebo, mean difference of 5.1 mg (95% CI: 7.0-3.2, I2 = 96.9%) morphine IV
equivalents; a 69% reduction in opioid rescue dosing was noted (odds ratio [OR]:
0.31, 95% CI: 0.16-0.80, I2 = 0.0%). A 61% reduction in postoperative nausea and
vomiting was also evident (OR: 0.39, 95% CI: 0.20-0.75, I2 = 60.7%). A reduction
in propofol induction dose was noted in the esmolol group (mean difference: -0.53
mg/kg, 95% CI: -0.63--0.44, I2 = 0.0%). A decrease in end-tidal desflurane
equivalent (mean difference: 1.70%, 95% CI: -2.39--1.02, I2 = 92.0%) and
intraoperative opioid usage (fentanyl equivalent, mean difference: 440 MUg, 95%
CI: -637--244, I2 = 99.6%) was observed in esmolol group. Esmolol had no effect
on the emergence time. Perioperative esmolol as an adjunct may reduce
postoperative pain intensity, opioid consumption, and postoperative nausea
vomiting. Given the heterogeneity, larger clinical trials are warranted to
confirm these findings.
PMID- 28413269
TI - Localization of epidural space: A review of available technologies.
AB - Although epidural analgesia is widely used for pain relief, it is associated with
a significant failure rate. Loss of resistance technique, tactile feedback from
the needle, and surface landmarks are traditionally used to guide the epidural
needle tip into the epidural space (EDS). The aim of this narrative review is to
critically appraise new and emerging technologies for identification of EDS and
their potential role in the future. The PubMed, Cochrane Central Register of
Controlled Clinical Studies, and Web of Science databases were searched using
predecided search strategies, yielding 1048 results. After careful review of
abstracts and full texts, 42 articles were selected to be included. Newer
techniques for localization of EDS can be broadly classified into techniques that
(1) guide the needle to the EDS, (2) identify needle entry into the EDS, and (3)
confirm catheter location in EDS. An ideal method should be easy to learn and
perform, easily reproducible with high sensitivity and specificity, identifies
inadvertent intrathecal and intravascular catheter placements with ease, feasible
in perioperative setting and have a cost-benefit advantage. Though none of them
in their current stages of development qualify as an ideal method, many show
tremendous potential. Some techniques are useful in patients with difficult
spinal anatomy and infants, and thus are complementary to traditional methods. In
addition to improving the existing technology, future research should aim at
proving the superiority of these techniques over traditional methods,
specifically regarding successful EDS localization, better safety profile, and a
favorable cost-benefit ratio.
PMID- 28413271
TI - ASSIST - Patient satisfaction survey in postoperative pain management from Indian
subcontinent.
AB - INTRODUCTION: To compare pain scores at rest and ambulation and to assess patient
satisfaction between the different modalities of pain management at different
time points after surgery. SETTINGS AND DESIGN: The ASSIST (Patient Satisfaction
Survey: Pain Management) was an investigator-initiated, prospective, multicenter
survey conducted among 1046 postoperative patients from India. MATERIAL AND
METHODS: Pain scores, patient's and caregiver's satisfaction toward postoperative
pain treatment, and overall pain management at the hospital were captured at
three different time points through a specially designed questionnaire. The
survey assessed if the presence of acute pain services (APSs) leads to better
pain scores and patient satisfaction scores. STATISTICAL ANALYSIS: One-way ANOVA
was used to evaluate the statistical significance between different modalities of
pain management, and paired t-test was used to compare pain and patient
satisfaction scores between the APS and non-APS groups. RESULTS: The results
indicated that about 88.4% of patients reported postoperative pain during the
first 24 h after surgery. The mean pain score at rest on a scale of 1-10 was 2.3
+/- 1.8 during the first 24 h after surgery and 1.1 +/- 1.5 at 72 h; the patient
satisfaction was 7.9/10. Significant pain relief from all pain treatment was
reported by patients in the non-APS group (81.6%) compared with those in the APS
(77.8%) group (P < 0.0016). CONCLUSION: This investigator-initiated survey from
the Indian subcontinent demonstrates that current standards of care in
postoperative pain management remain suboptimal and that APS service, wherever it
exists, is yet to reach its full potential.
PMID- 28413272
TI - An analysis of perioperative adverse neurological events associated with
anesthetic management at a Tertiary Care Center of a developing country.
AB - BACKGROUND AND AIMS: Existing literature on neurological complications related to
anesthesia is reported from affluent countries but the trends may vary in less
affluent countries. MATERIAL AND METHODS: The objective was to find the
associated factors contributing to neurological adverse events occurring within
48 h of anesthesia and surgery. The existing departmental morbidity and mortality
database was reviewed from 1992 to 2012 for major adverse neurological events. A
standardized methodology was used in reviewing and classifying the data. All
adverse events were predefined and categorized before filling the form into the
following headers; meningitis, cord/plexus/peripheral nerve injury, stroke,
paraparesis/paraplegia/quadriparesis/or quadriplegia, new onset postoperative
seizures, postoperative vocal cord injury, and a miscellaneous group. RESULTS:
During this period, 195,031 patients underwent anesthesia and twenty-nine
patients had major neurological morbidity within 48 h (1:6700). There were three
cases of meningitis/meningism, eight cases of cord, plexus or peripheral nerve
injury, seven of stroke, four had new onset seizures, one had quadriparesis, five
had vocal cord, and one had cranial nerve palsy. Forty-one percent cases received
regional anesthesia alone or in combination with the general. In six cases,
anesthesia was considered solely responsible. Human error contributed to 93% of
these events. CONCLUSION: This data has helped in identifying areas of concern
and can serve as a reference for further audits in the region.
PMID- 28413273
TI - Intraoperative low tidal volume ventilation strategy has no benefits during
laparoscopic cholecystectomy.
AB - BACKGROUND AND AIMS: Benefits of intraoperative low tidal volume ventilation
during laparoscopic surgery are not conclusively proven, even though its
advantages were seen in other situations with intraoperative respiratory
compromise such as one-lung ventilation. The present study compared the efficacy
of intraoperative low tidal volume ventilatory strategy (6 ml/kg along with
positive end-expiratory pressure [PEEP] of 10 cmH2O) versus one with higher tidal
volume (10 ml/kg with no PEEP) on various clinical parameters and plasma levels
of interleukin (IL)-6 in patients undergoing laparoscopic cholecystectomy.
MATERIAL AND METHODS: A total of 58 adult patients with American Society of
Anesthesiologists physical status I or II, undergoing laparoscopic
cholecystectomy were randomized to receive the low or higher tidal volume
strategy as above (n = 29 each). The primary outcome measure was postoperative
PaO2. Systemic levels of IL-6 along with clinical indices of intraoperative gas
exchange, pulmonary mechanics, and hemodynamic consequences were measured as
secondary outcome measures. RESULTS: There was no statistically significant
difference in oxygenation; intraoperative dynamic compliance, peak airway
pressures, or hemodynamic parameters, or the IL-6 levels between the two groups
(P > 0.05). Low tidal volume strategy was associated with significantly higher
mean airway pressure, lower airway resistance, greater respiratory rates, and
albeit clinically similar, higher PaCO2and lower pH (P < 0.05). CONCLUSION:
Strategy using 6 ml/kg tidal volume along with 10 cmH2O of PEEP was not
associated with any significant improvement in gas exchange, hemodynamic
parameters, or systemic inflammatory response over ventilation with 10 ml/kg
volume without PEEP during laparoscopic cholecystectomy.
PMID- 28413274
TI - Evaluation of decision-to-delivery interval in emergency cesarean section: A 1
year prospective audit in a tertiary care hospital.
AB - BACKGROUND AND AIMS: The American College of Obstetricians and Gynecologists
(ACOG) committee on professional standards and the National Institute of Clinical
Excellence (NICE) guidelines suggest that decision-to-delivery interval (DDI) and
emergency cesarean section (CS) should not be more than 30 min, and a delay of
more than75 min in the presence of maternal or fetal compromise can lead to poor
outcome. This prospective 1-year study was conducted on emergency CS in a
tertiary care hospital to evaluate the DDI, factors affecting it and to analyze
their effects on maternal and neonatal outcome. MATERIAL AND METHODS: A
structured proforma was used to analyze the data from all women undergoing
emergency CS, during a 1-year period, included in Category 1 and 2 of NICE
guidelines for CS. RESULTS: A total of 453 emergency CSs were evaluated, with a
mean DDI of 36.3 +/- 17.2 min for Category 1 CS and 38.1 +/- 17.7 min for
Category 2 CS (P > 0.05). Only 42.4% emergency CSs confirmed to the 30 min DDI
while 57.6% had a DDI of more than 30 min. Reasons of delay were identified as a
delay in shifting the patient to operation theater (22.1%), anesthesia factors
(18.1%), and lack of resources or manpower (16.1%). Maternal complications
occurred in 15 (3.3%) patients with 3 (0.7%) nonsurvivors having a DDI of 91.0 +/
97.0 min as compared to survivors with a DDI of 36.8 +/- 15.7 min, P = 0.001.
There was no significant association between DDI and occurrence of neonatal
complications. CONCLUSION: Failure to meet the current recommendations was
associated with adverse maternal outcomes, but not with adverse neonatal outcome.
PMID- 28413275
TI - Comparison of trapezius squeeze test and jaw thrust as clinical indicators for
laryngeal mask airway insertion in spontaneously breathing children.
AB - BACKGROUND AND AIMS: It is not known whether trapezius squeeze test (TPZ) is a
better clinical test than jaw thrust (JT) to assess laryngeal mask airway (LMA)
insertion conditions in children under sevoflurane anesthesia. MATERIAL AND
METHODS: After the Institutional Ethics Committee approval and written informed
parental consent, 124 American Society of Anesthesiologists I and II children of
2-8 years of age undergoing minor surgical procedures were randomized into TPZ
and JT groups. The children were induced with 8% sevoflurane in oxygen at a fresh
gas flow of 4 L/min. TPZ or JT was performed after 1 min of start of sevoflurane
and then every 20 s till the test was negative, when end-tidal (ET) sevoflurane
concentration was noted. Classic LMA of requisite size was inserted by a blinded
anesthetist and conditions at the insertion of LMA, insertion time, and the
number of attempts of LMA insertion were recorded. RESULTS: The mean LMA
insertion time was significantly longer (P < 0.001) for TPZ (145 +/- 28.7 sec)
compared to JT group (111.8 +/- 31.0 sec). ET sevoflurane concentration at the
time of LMA insertion was comparable in the two groups. LMA insertion conditions
were similar in the two groups. There was no difference between the two groups
regarding total number of attempts of LMA insertion. Heart rate (HR) decreased in
both groups after LMA insertion (P < 0.001) but TPZ group had significantly lower
HR compared with the JT group up to 5 min after LMA insertion (P = 0.03).
CONCLUSION: Both JT and TPZ are equivalent clinical indicators in predicting the
optimal conditions of LMA insertion in spontaneously breathing children; however,
it takes a longer time to achieve a negative TPZ squeeze test.
PMID- 28413276
TI - Comparison between ketamine and hyoscine for the management of postoperative
catheter-related bladder discomfort: A randomized controlled double-blind study.
AB - BACKGROUND AND AIM: Postoperative catheter-related bladder discomfort (CRBD) can
be a distressing complication for patients in whom a urinary catheter was
inserted intraoperatively and is accompanied with patients' dissatisfaction. This
trial investigated the efficacy of hyoscine and ketamine on treatment of
postoperative CRBD in patients undergoing various surgeries. MATERIAL AND
METHODS: This was a prospective randomized, double-blind study, which included 60
American Society of Anesthesiologists Class I-II male patients undergoing
elective nonurological operations requiring intraoperative urinary
catheterization under general anesthesia after ethical approval and written
informed consent. Patients were allocated randomly into two groups: The hyoscine
group (H group) (n = 30) received 20 mg of hyoscine intravenously and ketamine
group (K group) (n = 30) received 0.25 mg/kg of ketamine intravenously
immediately after the occurrence of CRBD. The severity of CRBD was assessed at 0,
1, 2, and 4 h postoperatively. Adverse effects of hyoscine and ketamine were also
examined. Data were summarized using mean +/- standard deviation, and comparisons
between groups were done by unpaired t-test. For comparison of serial
measurements within each group, ANOVA was used. RESULTS: There was a significant
difference between the two groups in the severity of CRBD measured by visual
analog scale score only 30 min after drug administration where it was higher in
ketamine group (44.50 +/- 7.70) compared to hyoscine group (36.00 +/- 8.55) (P <
0.001), otherwise there was no significant difference at other time points
between the two groups, also there was a significant rise in heart rate in
hyoscine group but no significant difference in mean arterial pressure.
CONCLUSION: Intravenous hyoscine 20 mg is more effective in control of CRBD than
ketamine (0.25 mg/kg) in the first 30 min; later on they have the same effect.
PMID- 28413277
TI - Efficacy of dexmedetomidine with ropivacaine in supraclavicular brachial plexus
block for upper limb surgeries.
AB - BACKGROUND AND AIMS: The primary aim of this study was to evaluate the effect of
addition of dexmedetomidine on the duration of analgesia in patients undergoing
upper limb surgeries under supraclavicular brachial plexus block. MATERIAL AND
METHODS: Sixty patients of American Society of Anesthesiologists physical status
I/II/III undergoing elective upper limb surgeries under supraclavicular brachial
plexus block using nerve stimulator were randomized into two groups. Group A (n =
30) received 30 mL 0.5% ropivacaine and 1 mL normal saline, and Group B (n = 30)
received 30 mL 0.5% ropivacaine and 1 MUg/kg of dexmedetomidine. The primary
outcome was the duration of analgesia. Secondary outcomes included time to onset
and duration of sensory/motor blockade. STATISTICAL ANALYSIS: Results on
continuous measurements are presented as mean +/- standard deviation and compared
using Student's unpaired t-test. Results on categorical measurements are
presented in number (%) and compared using Chi-square test. RESULTS: Onset of
sensory and motor block in Group A (13.0 +/- 4.1 and 23.5 +/- 5.6 min) was slower
than those in Group B (9.5 +/- 5.8 and 15.6 +/- 6.3 min; P = 0.009 for sensory
and P < 0.001 for the motor block). Duration of sensory and motor block in Group
A (400.8 +/- 86.6 and 346.9 +/- 76.9 min) was shorter than those in Group B
(630.6 +/- 208.2 and 545.9 +/- 224.0 min; (P < 0.001). The duration of analgesia
in Group A (411.0 +/- 91.2 min) was shorter than that in Group B (805.7 +/- 205.9
min; P < 0.001). The incidence of bradycardia and hypotension was higher in Group
B than in Group A (P < 0.001). CONCLUSION: Perineural dexmedetomidine with
ropivacaine provides prolonged postoperative analgesia, hastens the onset of
sensory and motor block and prolongs the duration of the supraclavicular brachial
plexus block.
PMID- 28413278
TI - Work-related stress: A survey of Indian anesthesiologists.
AB - BACKGROUND AND AIMS: Work-related stress is common among medical caregivers and
concerns all perioperative care providers. Although anesthesiologists are known
to experience stress, there are limited Indian data addressing this issue. This
survey was conducted among Indian anesthesiologists to determine their awareness
about work stress and views regarding prevention programs. MATERIAL AND METHODS:
A survey questionnaire was distributed to delegates visiting the exhibits at the
national anesthesiology conference in 2011. The questionnaire had ten questions
on the work pattern, five on work-related stress, nine on opinion regarding the
need and willingness to participate in stress-related programs. RESULTS: There
were 1178 responders. Forty-three percent were faculty in medical institutions,
26% were residents and 25% were in free-lance practice. Ninety-one percent of
participants rated their stress as moderate-extreme. There was a significant
correlation between the amount of stress and working for more than 8 h (P <
0.001), handling high risk patients (P = 0.002), working on weekends (P = 0.002),
and carrying work back home (P < 0.001). Forty-one percent of respondents were
very satisfied professionally. Seventy-six percent of doctors agreed that the
questionnaire had made them think about work stress. Eighty-four percent of
participants felt the need for stress management programs and 69% expressed their
willingness to participate in the same. CONCLUSION: The majority of participants
rated their stress as moderate-extreme and was higher in anesthesiologists
working long hours, over the weekend and those handling high-risk patients. A
majority of participants felt the survey made them think about work-related
stress and expressed their willingness to participate in stress management
programs.
PMID- 28413279
TI - Comparing slow and rapid bolus of ephedrine in pregnant patients undergoing
planned cesarean section under spinal anesthesia.
AB - BACKGROUND AND AIMS: While ephedrine was the preferred drug for treating spinal
induced hypotension in pregnancy, its use has declined because of resultant fetal
acidosis. The objective of this randomized control trial was to compare the
effects of a slow and rapid bolus of ephedrine on fetal acidosis, maternal blood
pressure, and heart rate (HR) during cesarean section performed under spinal
anesthesia. MATERIAL AND METHODS: Eighty full-term parturients scheduled for
cesarean section under spinal anesthesia were randomly allocated into two groups.
While both groups received 6 mg of ephedrine to treat hypotension, Group R (n =
40) received it as a rapid intravenous bolus and Group S (n = 40) received it
slowly over 20 s with an infusion pump. The maternal vital parameters were
recorded until delivery of the baby using a video camera. Umbilical cord blood
was obtained using the three clamp method. Hemodynamic parameters, fetal
acidosis, total number of ephedrine bolus used, peak HR after the ephedrine
bolus, and occurrence of postoperative nausea and vomiting (PONV) were compared
between the groups. RESULTS: Mean increase in HR and blood pressure were
significantly higher in Group R than the Group S after the first ephedrine bolus.
Umbilical artery pH was significantly lower in Group R than in Group S (7.2 [6.8
7.3] vs. 7.3 [7.3-7.4], P < 0.01). A total number of ephedrine boluses were
comparable in the two groups. 35% of the patients had PONV in Group R, whereas
none had it in Group S (P < 0.01). CONCLUSION: Slow bolus of ephedrine is better
than rapid bolus to treat spinal-induced hypotension during cesarean section in
view of less fetal acidosis.
PMID- 28413280
TI - Comparison of sevoflurane and propofol for laryngeal mask airway insertion and
pressor response in patients undergoing gynecological procedures.
AB - BACKGROUND AND AIMS: A popular method of providing anesthesia for laryngeal mask
airway (LMA) insertion is with the use of propofol. However, bolus propofol has
been associated with adverse effects such as hypotension, apnea and pain on
injection. Hence, time is needed to search an alternative. We aimed to compare
the induction characteristics, ease of LMA insertion, hemodynamic changes and
complications with inhalation of 8% sevoflurane vital capacity breath and
propofol. MATERIAL AND METHODS: A prospective randomized study of 60 American
Society of Anesthesiologists' Grade I and II patients was conducted and
distributed among two groups with 30 each undergoing gynecological procedures
under general anesthesia. Group P received the injection propofol and Group S
received sevoflurane. At the end point of induction, the LMA insertion was
attempted. Scoring systems were used to grade the conditions for insertion of the
LMA. Induction, LMA insertion characteristics, hemodynamic changes, complications
were assessed. Data were recorded and analyzed. Comparison among the study groups
was done with unpaired t-test, Mann-Whitney test and Chi-square test. RESULTS:
Sevoflurane took a longer time for induction and for LMA insertion than propofol.
There was no statistically significant difference between the two groups, with
respect to LMA insertion characteristics, heart rate, mean arterial pressure. It
is concluded that sevoflurane is associated with good hemodynamic stability and
may prove useful incases where propofol is to be avoided. However, the ease of
insertion provided with propofol is better.
PMID- 28413281
TI - A comparative study of the effect of clonidine, fentanyl, and the combination of
both as adjuvant to intrathecal bupivacaine for postoperative analgesia in total
abdominal hysterectomy.
AB - BACKGROUND AND AIMS: The aim of this study was to evaluate the level of sensory
block, onset and duration of motor block, postoperative analgesia, and adverse
effects of combination of clonidine and fentanyl given intrathecally with
hyperbaric bupivacaine (HB). MATERIAL AND METHODS: Three hundred and twenty eight
patients were randomized into four groups. Group bupivacaine (group B) received
15 mg of HB; group bupivacaine clonidine (group BC) received 15 mg of HB plus 25
MUg clonidine; group bupivacaine fentanyl (group BF) received 15 mg of HB plus 25
MUg fentanyl and group bupivacaine clonidine fentanyl (group BCF) received 15 mg
of HB plus 25 MUg clonidine and 25 MUg fentanyl intrathecally. All groups were
evaluated for level of sensory block, onset and duration of motor block,
postoperative analgesia, VAS score, sedation score and adverse effects of study
drugs. All the data were analyzed using unpaired t-test. P < 0.05 was considered
significant. RESULTS: The level of sensory block, onset, and duration of motor
block were comparable in all groups. Total duration of analgesia was 407.3 +/- 20
min in group BCF compared to 242.1 +/- 2 min and 209.2 +/- 16 in groups BC and
BF, respectively. Lesser doses of rescue analgesic were required in group BCF.
The time interval from intrathecal injection to two-segment regression was
statistically significant in study groups. Only 2.4% patients showed mild
sedation in BCF group. CONCLUSION: We found that combination of intrathecal
clonidine and fentanyl along with bupivacaine increases the total duration of
analgesia without significant side effects.
PMID- 28413283
TI - Is it time to separate consent for anesthesia from consent for surgery?
PMID- 28413282
TI - Comparison of success of tracheal intubation using Macintosh laryngoscope
assisted Bonfils fiberscope and Truview video laryngoscope in simulated difficult
airway.
AB - BACKGROUND AND AIMS: Restriction of head and neck movements prevents the
alignment of the oral, pharyngeal, and laryngeal axes and increases the incidence
of difficult tracheal intubation in patients with cervical spine fractures. Video
laryngoscopes have gained an important role in the management of difficult
intubation, especially in situations with limited head and neck movements. This
study compares the success of intubation using Macintosh laryngoscope assisted
Bonfils(r) fiberscope (ML-BF) with TruviewPCD video laryngoscope (TV) in patients
with simulated restricted head and neck movements. MATERIAL AND METHODS: One
hundred and fifty-two patients satisfying the inclusion criteria were randomly
allocated to two groups of 76 each. Patients were made to lie supine on the table
without a pillow and a soft collar was used to restrict head and neck movements.
After a standardized premedication-induction sequence, tracheal intubation was
done either with ML-BF or TV. Success of intubation, time taken for successful
intubation, hemodynamic changes, airway trauma, and postoperative oropharyngeal
morbidity were noted. RESULTS: Intubation was successful in all the 76 patients
in direct laryngoscopy-Bonfils fiberscope group and 75 out of 76 patients in TV
group within the specified time (90 s). The median time taken for successful
intubation with TV and ML-BF were 44 (range 26-80) s and 49 (range 28-83) s,
respectively. Hemodynamic changes, airway trauma, and postoperative oropharyngeal
morbidity were similar in both groups. CONCLUSION: Both TV and ML-BF are equally
effective for successful tracheal intubation in patients with simulated
restricted head and neck movements. In cases of difficult laryngeal visualization
with routine Macintosh laryngoscope, Bonfils can be used as an adjunct to achieve
successful intubation in the same laryngoscopy attempt.
PMID- 28413284
TI - Combined mitral and aortic stenosis in parturient: Anesthesia management for
labor and delivery.
AB - Maternal heart disease complicates 0.2-3% of pregnancies. The optimal management
of the pregnant patient with cardiac disease depends on the co-operative efforts
of the obstetrician, the cardiologist and the anesthesiologist involved in
peripartum care. A comprehensive understanding of physiology of pregnancy and
pathophysiology of underlying cardiac disease is of primary importance in
provision of obstetric analgesia or anesthesia for these high-risk groups of
patients. We report a successful and uncomplicated use of epidural anesthesia for
labor and delivery in patient with combined aortic and mitral stenosis.
PMID- 28413286
TI - Transversus abdominis plane catheters for postoperative pain relief in pediatric
patients.
AB - Regional techniques provides excellent post operative pain relief in pediatric
patients. Transversus abdominis plane (TAP) block is a newer regional technique
available. Though there is emerging evidence proving the efficacy of TAP blocks,
there is limited literature on use of TAP catheters in pediatric patients. TAP
catheters were placed in two children following laparotomy with transverse
incisions and in both epidural was avoided, with good post operative pain relief.
Ultrasound guidance was used in one child, while in the other the catheter was
placed under direct vision after dissection of the plane between transversus
abdominis and internal oblique. Intermittent boluses of high volumes of local
anesthetic (0.6-0.7 ml/kg) were used through the TAP catheter, ensuring that the
maximum permissible level of bupivacaine was not exceeded. In adults, continuous
abdominal catheters have found a place for post-operative pain management, when
epidural analgesia is contraindicated. At present, the use of TAP catheters by
pediatric anesthesiologists is limited, though there exists diverse clinical
scenarios when these catheters may be of benefit. Contraindication of neuraxial
blockade and septic patients are the two scenarios we have reported. In
conclusion, TAP catheters are effective analgesia technique for laparotomies with
transverse incision in pediatric patients.
PMID- 28413285
TI - Disseminated intravascular and intracardiac thrombosis after cardiopulmonary
bypass.
AB - Massive intracardiac and intravascular thrombosis is a rare complication
following cardiopulmonary bypass (CPB). Most of the cases of the disseminated
thrombosis have been reported in patients undergoing complex cardiac surgeries
and those receiving antifibrinolytic agents during CPB. We report the occurrence
of disseminated intravascular and intracardiac thrombosis after CPB in a patient
undergoing mitral valve replacement in which no antifibrinolytic agent was used.
The possible pathophysiology and management of the patient is discussed.
PMID- 28413287
TI - De-addiction: A new risk for anesthesia.
PMID- 28413288
TI - Obtaining external jugular venous access in the prone-positioned patient.
PMID- 28413289
TI - Intra-operative mechanical ventilation in amebic liver abscess surgery: Another
paradigm.
PMID- 28413290
TI - Unusual case of endotracheal tube obstruction by caseous necrotic material.
PMID- 28413291
TI - Green urine: A cause for concern?
PMID- 28413292
TI - LMA Proseal for the surgical procedures in prone positioning.
PMID- 28413293
TI - In response to: Comparison of paravertebral and interpleural block in patients
undergoing modified radical mastectomy.
PMID- 28413294
TI - Response to the letter for the article: Use of transversus abdominis plane block
as an anesthetic technique in a high-risk patient for abdominal wall surgery.
PMID- 28413295
TI - Emergency airway management of intratracheal tumor in a patient with respiratory
distress.
PMID- 28413296
TI - Immediate onset of postdural puncture headache after spinal anesthesia.
PMID- 28413297
TI - Ketamine-induced QTc interval prolongation.
PMID- 28413298
TI - Anorectal Malformation: Issues Beyond Definitive Surgery.
PMID- 28413299
TI - Congenital Pouch Colon.
AB - Congenital pouch colon (CPC) is an unusual abnormality in which a pouch-like
dilatation of a shortened colon is associated with an anorectal malformation. It
is categorized into four subtypes (Types I-IV) based on the length of normal
colon proximal to the colonic pouch. In males, the pouch usually terminates in a
colovesical fistula just proximal to the bladder neck. In girls, the terminal
fistula opens either into the urethra or in the vestibule, close to the urethral
opening. Girls usually have a double vagina with a wide inter-vaginal bridge, a
monocornuate uterus on each side, and urinary incontinence due to a widely open
bladder neck. Associated major malformations are uncommon with CPC but sometimes,
especially in reports from outside India, major abnormalities are present
suggesting an early, severe error in embryogenesis. The more severe Types I/II
CPC can usually be diagnosed by a large gas shadow or air-fluid level on X-Ray
abdomen. For all subtypes of CPC, it is preferable to preserve a segment of the
pouch by fashioning a narrow colonic tube for pull-through, the technique known
as coloplasty or tubular colorraphy. Girls need additional management of the
genitourinary abnormalities. Postoperatively, fecal continence levels are usually
poor, especially with Types I/II CPC.
PMID- 28413300
TI - Anorectal Agenesis with Rectovaginal Fistula: A Rare/Regional Variant.
AB - AIMS AND OBJECTIVES: The anatomical types of female anorectal malformation (ARM)
are complex and include several rare and regional variants. The aim of this
report is to highlight the diagnosis and management of cases of anorectal
agenesis with rectovaginal fistula (RVF). MATERIALS AND METHODS: This is a
retrospective chart review of cases of RVF who underwent definitive surgery
between November 2000 and September 2016 in a single institution. RESULTS: Of the
244 female patients with anorectal anomalies treated in our institution over a 16
year period, there were 15 cases of RVF with anorectal agenesis giving it an
incidence of 6%. All cases of RVF with anorectal agenesis presented with absence
of anal opening, varying degree of abdominal distension, and history of passage
of fecal matter per vaginum. The mean age of presentation was 3 months (newborn
to 1 year). Sigmoid colostomy was done in 13 cases. Distal colostogram
demonstrated high RVF which was further confirmed by examination under anesthesia
(EUA) and endoscopy before definitive surgery. With the posterior sagittal
approach, division of the RVF and anorectoplasty was possible in 14 cases;
however, one patient required an abdominal mobilization of the colon for pull
through due to a very short distal bowel segment. During a mean postoperative
follow-up of 5 years, cosmetic and functional results were satisfactory.
CONCLUSION: RVF with anorectal agenesis is a rare/regional variant of female
ARMs. Clinical examination along with distal colostogram, EUA, and endoscopy
clinches the diagnosis. Anorectal reconstruction by posterior sagittal
anorectoplasty results in a satisfactory outcome.
PMID- 28413301
TI - Anorectal Malformations in Males: Pros and Cons of Neonatal versus Staged
Reconstruction for High and Intermediate Varieties.
AB - BACKGROUND: High and intermediate types of anorectal malformations (ARMs) in male
neonates may be managed either by primary neonatal reconstruction without
colostomy cover or by traditional policy of staged reconstruction after neonatal
colostomy. Posterior sagittal anorectoplasty (PSARP) is the current widely
practiced reconstructive technique with varied results. AIM: To assess our
functional results of PSARP without colostomy in male neonates with high and
intermediate ARMs compared to 3-stage (neonatal colostomy - PSARP - colostomy
closure) methodology in a high volume tertiary care institution of a developing
country. PATIENTS AND METHODS: The number of colostomies performed for male
high/intermediate anomalies and the number of babies who completed 3-stage
reconstruction during a 10-year period is analyzed. The outcome of primary
neonatal PSARPs during the same period was analyzed. Eighty primary PSARPs were
compared to 81 staged reconstructions for outcome analysis, using Kelly score.
RESULTS: A total of 453 colostomies were performed, but only 253 of them
completed all stages of reconstruction (52%). Good continence was achieved in 45%
of cases of primary PSARP versus 26% in 3-staged surgery. CONCLUSIONS: Primary
PSARP in neonatal period without colostomy is a good option for high and
intermediate ARMs in males if the treating surgeon is reasonably skilled in
neonatal surgery and PSARP procedures.
PMID- 28413302
TI - Primary Definitive Procedure versus Conventional Three-staged Procedure for the
Management of Low-type Anorectal Malformation in Females: A Randomized Controlled
Trial.
AB - INTRODUCTION: Females with Krickenbeck low-type anorectal malformations -
vestibular fistula (VF) and perineal fistula (PF) - are managed either by a
primary definitive or conventional three-staged approach. Ultimate outcome in
these children may be affected by wound dehiscence leading to healing by
fibrosis. Most of the literature favors one approach over other based on
retrospective analysis of their outcomes. Whether a statistically significant
difference in wound dehiscence rates between these approaches exists needed to be
seen. MATERIALS AND METHODS: A randomized controlled trial for girls <14 years
with VF or PF was done. Random tables were used to randomize 33 children to Group
I (primary procedure) and 31 to Group II (three-staged procedure). Statistical
analysis was done for significance of difference (P < 0.05) in the primary
outcome (wound dehiscence) and secondary outcomes (immediate and early
postoperative complications). RESULTS: Of the 64 children randomized, 54 (84%)
had VF. Both groups were comparable in demography, clinical profile and age at
surgery. The incidence of wound dehiscence (39.4% vs. 18.2%; P = 0.04), immediate
postoperative complications (51.5% vs. 12.9%; P = 0.001), and early postoperative
complications (42.4% vs. 12.9%; P = 0.01) was significantly higher in Group I as
compared to Group II. Six of 13 children (46.2%) with dehiscence in Group I
required a diverting colostomy to be made. CONCLUSIONS: Females with VF or PF
undergoing primary definitive procedure have a significantly higher incidence of
wound dehiscence (P = 0.04), immediate (P = 0.001) and early postoperative
complications (P = 0.01).
PMID- 28413303
TI - Role of Interferential Therapy in Children with Fecal Incontinence Postanorectal
Malformation Surgeries.
AB - BACKGROUND: Anorectal malformation (ARM) is one of the most common pediatric
surgical problems dealt in day-to-day practice. Although the outcome of surgery
has improved a great deal over the last three decades fecal incontinence (FI) is
still a common long-term morbidity that affects the quality of life of these
patients. Bowel wash (BW) program with pelvic floor exercise are standard care of
management for these patients. This study was undertaken to assess the role of
interferential therapy (IFT) along with BW compared to BW alone in the management
of FI. METHODOLOGY: Twenty-four children more than 2-year-old age previously
operated for malformation and having FI with Kelly score <4 were recruited and
assigned to one of the two groups. One group was given standard BW regimen and
the other BW with IFT for 3 months. Posttherapy Kelly scoring was done, and the
results were compared. RESULTS: IFT with BW provided no added advantage over BW
alone for the treatment of FI in patients of ARMs. CONCLUSION: The time-tested
modality of BW is the cornerstone in the management of FI.
PMID- 28413304
TI - Simultaneous Single-staged Repair of Anorectal Malformation with
Tracheoesophageal Fistula: Lessons Learned.
AB - INTRODUCTION: Anorectal malformation (ARM) associated esophageal atresia (EA)
with tracheoesophageal fistula (TEF) spawns special therapeutic propositions. The
outcome of these patients banks on numerous factors. We performed this study with
an aim to compare the outcome of single-staged simultaneous primary repair of
both anomalies versus staged repair of these disorders. MATERIALS AND METHODS:
Retrospective review of cases with ARM and associated EA with TEF managed over a
period of 5 years from July 2010 to June 2015 after ethical approval was
undertaken. Patients were split into two groups based on whether they underwent
staged repair (Group A) or single-staged simultaneous primary repair of ARM with
TEF (Group B). Patient's records were analyzed for demography, weight,
gestational age, associated anomaly, preoperative and postoperative sepsis screen
results, early and late postoperative complications (at least up to 1 year of
age). Patient's Kelly score for continence at the age of 3 years or more was
compared. OBSERVATION: A total of 28 were included in the study. Among these, 17
were managed with staged procedure for ARM (Group A), whereas 11 underwent
simultaneous single-stage repair of ARM with TEF (Group B). No difference in
continence score was observed in outcome between the two groups (P = 0.96).
Overall mortality in Group A at 1-year follow-up was 52.9% and in Group B was
43.4%. CONCLUSION: The simultaneous single-staged primary repairs result in
better long-term outcome in our setup.
PMID- 28413305
TI - Solitary Functioning Kidney in High Anorectal Malformation.
AB - AIM: A solitary functioning renal unit in high anorectal malformation may harbor
anomalies in the upper/lower urinary tract that further compromise renal function
and accelerate hyperfiltration injury. We aimed to analyze the clinical course,
management, and outcome of children with a solitary renal unit and high anorectal
malformation. MATERIALS AND METHODS: A cohort of solitary renal units in
anorectal malformation managed between 2000 and 2015 with a defined protocol at a
pediatric nephro-urology clinic are included in the study. Investigations and
management were individualized according to issues in the agenetic/dysplastic
unit, solitary functioning unit, or bladder-urethra. Clinical details,
management, and outcome were analyzed. RESULTS: Of 53 cases of high anorectal
malformation with urologic anomalies, 17 (32%) had single kidneys. Majority
(10/17, 59%) had another complicating urinary tract anomaly, four being uremic at
presentation. Nearly half had multiple urinary infections including epididymo
orchitis unrelated to the rectourinary fistula and warranted additional stoma
(bowel/urinary) or other urinary tract surgery. At a mean follow-up of 70 months,
majority (14/17, 82%) have a preserved solitary renoureteric unit while the
remaining three await renal replacement therapy. CONCLUSION: Solitary functioning
renal units associated with high anorectal malformation in children need
meticulous investigation and surveillance to facilitate renal preservation. The
implications of the associated rectourinary fistula, vesicoureteral reflux,
urinary infections including epididymo-orchitis, and other urinary tract
anomalies on the conventional surgical management are illustrated.
PMID- 28413306
TI - Urogenital Management in Cloaca: An Alternative Approach.
AB - INTRODUCTION: In the management of cloaca, there is concern that dissection of
the urogenital sinus in early childhood with the aim of total anatomical
correction is hazardous. Avoiding such mobilization and providing mitrofanoff
channel, when needed, till peripubertal period reduces complications and is
technically easier. MATERIALS AND METHODS: Forty-three cases of cloaca were
managed in the period 2004-2016. Case records and radiology were reviewed
retrospectively. The follow-up evaluation was done by looking into voiding
history, bowel movements, and menstruation history. RESULTS: There were three
groups of children, namely, those with no reconstruction done elsewhere except a
diverting fecal stoma (Group I, n = 25), those who had undergone anorectal
correction elsewhere with no attempt at urogenital reconstruction (Group IIA, n =
13), and those with attempted bowel and genitourinary reconstruction elsewhere
(Group IIB, n = 5). The Group I children (one still awaiting reconstruction)
underwent early rectal reconstruction followed by expectant management of the
urogenital apparatus. The 18 referred cases had multiple problems, chiefly
urogenital, of congenital or iatrogenic origin. While urinary reconstruction
included bladder augmentation, ileal neobladder, bladder neck closure, and
ureteric reimplantation, the foundation of urinary management was intermittent
catheterization through mitrofanoff stoma and the avoidance of any dissection of
the cloacal common channel. Surgery on the genital tracts included drainage of
hydrocolpos, perineal surgery for low vaginae and abdominoperineal vaginoplasty
for high vaginae in the peripubertal period with or without bowel
supplementation. Spontaneous voiding was maintained in 17 of 25 (68%) Group I
girls (including one death later from intestinal complications), 7 of 13 (54%),
Group IIA girls, and 1 of 5 (20%) Group IIB girls. Painless menstruation was
noted in eight postpubertal girls, three through the cloacal channel (awaiting
reconstruction) and five through the reconstructed vagina. Most of the children
are on a bowel management program for fecal cleanliness with washouts through the
neoanus or Malone's stoma. CONCLUSION: We report a nonconventional approach to
cloaca based on avoiding dissection of or around the common channel for
urethrovaginal reconstruction, opting for mitrofanoff stoma for intermittent
catheterization, when needed, and late vaginal reconstruction. We believe this
approach has reduced the overall need for intermittent catheterization.
PMID- 28413307
TI - Laparoscopic-assisted Anorectoplasty: A Single-center Experience.
AB - AIM: To assess the modifications in the technique of laparoscopic-assisted
anorectal pull-through (LAARP) practiced at our institute and to analyze the
postoperative outcome and associated complications. MATERIALS AND METHODS: A
retrospective study was done to analyze the results for LAARP procedure done for
high anorectal malformations (ARMs) from January 2001 to May 2016. A total of 68
patients had undergone LAARP, with 62 male and 6 female children. Staged
procedure was done in 55 patients and one child with rectovestibular fistula of 5
months of age had a single-stage procedure. Technical modifications such as
traction over the fistula which helps in identification and dissection of the
puborectalis muscle, dividing the fistula without ligation, railroading with
Hegar's dilators over the suction cannula which creates adequate pull-through
channel, have helped save time and make the procedure simpler. The patients were
followed up with clinical evaluation and continence scoring. RESULTS: All the
patients withstood surgery well. One patient with rectovesical fistula required
conversion to gain adequate length of the distal rectum, for whom the colostomy
was closed and relocated at splenic flexure level. The complications were mucosal
prolapse (8 cases), anal stenosis (5), adhesive obstruction (2), distal rectal
necrosis (3), and urethral diverticulum (2). The progress has been satisfactory
and weight gain is adequate. 71.15% patients had good continence on follow-up.
CONCLUSION: LAARP procedure is safe for high ARMs with good continence and
correctable side effects. It has completely replaced posterior sagittal
anorectoplasty procedure for high anomalies in our practice.
PMID- 28413308
TI - Congenital Pouch Colon with Rectal Atresia Revisited.
AB - We are adding two cases of congenital pouch colon with rectal atresia (RA) to the
already published five cases. The presentation of RA is often delayed owing to
the presence of normal anus, however, clinical evaluation, plain abdominal
radiograph, and urine examination for meconuria, may help in detecting this rare
association early.
PMID- 28413309
TI - Type V Congenital Pouch Colon: An Extremely Rare Variant of Anorectal
Malformations.
AB - Type V is the rarest form of congenital pouch colon with only four cases reported
till date. We report this anomaly in a 6-month-old boy. He was managed
successfully with excision of distal pouch and coloplasty of proximal pouch along
with abdominoperineal posterior sagittal anorectoplasty. We recommend
preservation of proximal pouch in such cases.
PMID- 28413310
TI - Females with Externally Visible but Stenosed Fecal Orifice - Low or High
Anorectal Malformation.
AB - We report four female children with externally visible but stenosed fecal orifice
which proved to be a high anorectal malformation (Type IV pouch colon). They were
managed by an abdominoperineal approach with excellent results. We emphasize the
correct recognition of this pathology.
PMID- 28413311
TI - Persistent Cloaca: A Long-term Follow-up Study.
PMID- 28413313
TI - Additional Risk Minimisation Measures for Medicinal Products in the European
Union: A Review of the Implementation and Effectiveness of Measures in the United
Kingdom by One Marketing Authorisation Holder.
AB - INTRODUCTION: Additional risk minimisation measures (aRMMs) for medicinal
products are necessary to address specific important safety issues which may not
be practically achieved through routine risk management measures alone. The
implementation and determination of effectiveness for aRMMs can be a challenge as
it involves multiple stakeholders. It is therefore important to have concise
objectives to avoid undue burden on patients, healthcare professionals and the
healthcare system. AIM: The aim of this study was to examine how aRMMs are
implemented and how effectiveness is assessed in the European Union (EU) using
practical examples from Roche Products Limited in the United Kingdom (UK)
(referred to as the 'Company'). METHODS: Three centrally authorised products were
selected from the Company's portfolio, each of which had aRMMs to address
important safety concerns; specifically, teratogenicity, medication error and
infections. The implementation of EU aRMMs, effectiveness checks and specific UK
activities were analysed. Hard copy folders and electronic sites for Company
aRMMs were used to assess process indicators. Periodic benefit-risk evaluation
reports for specified time intervals and the Company safety database was used in
checking safety outcomes for the selected products. For each product, the
effectiveness of aRMMs was analysed based on specific process indicators and the
subsequent safety outcomes. Literature searches were performed on scientific
databases for the purposes of the broader study. RESULTS: The main process
indicators in measuring effectiveness of Company aRMMs were distribution metrics
for educational materials, assessment of awareness and clinical actions among
healthcare professionals (HCPs). Case reports of pregnancy, medication errors and
progressive multifocal leukoencephalopathy (PML) were the outcome indicators for
Erivedge(r)?, Kadcyla(r)? and MabThera(r) (the latter specifically in autoimmune
indications: rheumatoid arthritis, granulomatosis with polyangiitis and
microscopic polyangiitis) respectively. No pregnancy, one medication error and 10
confirmed PML cases were reported for Erivedge(r)?, Kadcyla(r)? and MabThera(r)
respectively. CONCLUSIONS: For the chosen products, a reasonable awareness of
aRMMs amongst HCPs is a positive indicator of success in the use of educational
materials. However, low response rates from surveys indicate that voluntary
feedback may not always achieve the desired level of response in measuring
effectiveness. There is a challenge in determining overall effectiveness of aRMMs
due to a lack of defined success thresholds. Further regulatory guidance to
outline the elements and desired outcomes of aRMMs will be useful for consistency
in achieving successful outcomes.
PMID- 28413312
TI - Low-Income, African American, Adolescent Mothers' Depressive Symptoms, Perceived
Stress, and Social Support.
AB - The purpose of this descriptive repeated-measures study was to describe
depressive symptom patterns and report changes over time in levels of perceived
stress and social support depending on patterns of depressive symptoms in single,
low-income, African American, adolescent mothers during the initial, 6-month
postpartum period. Thirty-five adolescent subjects between the ages of 16 and 22
years old were recruited at health care clinics in two Midwestern cities. Data
collections by advanced practice nurses were completed at 1 week, 6 weeks, 3
months, and 6 months postpartum at mothers' homes. Established instruments were
used to measure depressive symptoms, perceived stress and social support. Results
indicated 63% of adolescent mothers' experienced depressive symptoms sometime
during this transition period and 11.4% of these subjects had depressive symptoms
at all 4 time points. Depressive symptoms were associated with perceived stress
at each time point. Emotional support was inversely associated with depressive
symptoms at 2 of the 4 time points. Depressive symptoms and problematic support
were significantly related at 3 months and 6 months. Although single, low-income,
African American, adolescent mothers are considered a high risk group, some are
at even greater risk. This extremely high risk group have depressive symptoms
throughout the first 6 months postpartum with the highest level of perceived
stress and the most variability in social support relative to groups that were
never depressed or were in and out of depression. More studies are needed to
understand how to best help these high risk adolescents successfully transition
to motherhood.
PMID- 28413314
TI - Implications of red Panax ginseng in oxidative stress associated chronic
diseases.
AB - The steaming process of Panax ginseng has been reported to increase its major
known bioactive components, ginsenosides, and, therefore, its biological
properties as compared to regular Panax ginseng. Biological functions of red
Panax ginseng attenuating pro-oxidant environments associated with chronic
diseases are of particular interest, since oxidative stress can be a key
contributor to the pathogenesis of chronic diseases. Additionally, proper
utilization of various biomarkers for evaluating antioxidant activities in
natural products, such as ginseng, can also be important to providing validity to
their activities. Thus, studies on the effects of red ginseng against various
diseases as determined in cell lines, animal models, and humans were reviewed,
along with applied biomarkers for verifying such effects. Limitations and future
considerations of studying red ginseng were been discussed. Although further
clinical studies are warranted, red ginseng appears to be beneficial for
attenuating disease-associated symptoms via its antioxidant activities, as well
as for preventing oxidative stress-associated chronic diseases.
PMID- 28413315
TI - The involvement of ginseng berry extract in blood flow via regulation of blood
coagulation in rats fed a high-fat diet.
AB - BACKGROUND: The present study investigated the effect of ginseng berry hot water
extract (GBx) on blood flow via the regulation of lipid metabolites and blood
coagulation in rats fed a high-fat diet (HFD). METHODS: Sixty rats were divided
into five groups in descending order of body weight. Except for the control
group, the other four groups were fed a HFD containing 45% kcal from fat for 11
wk without GBx. GBx groups were then additionally treated by gastric gavage with
GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or
150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the
effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation
assay, and histological analysis were performed. RESULTS: In the experiments to
measure the serum levels of leptin and apolipoprotein B/A, GBx treatment
attenuated the HFD-induced increases in these metabolites (p < 0.05). Adiponectin
and apolipoprotein E levels in GBx-treated groups were significantly higher than
the HFD group. Prothrombin time and activated partial thromboplastin time were
increased in all GBx-treated groups. In the GBx-treated groups, the serum levels
of thromboxane A2 and serotonin were decreased and concentrations of serum
fibrinogen degradation products were increased (p < 0.05). Moreover,
histomorphometric dyslipidemia-related atherosclerotic changes were significantly
improved by treatment with GBx. CONCLUSION: These results suggest the possibility
that GBx can ameliorate blood flow by decreasing intima-media thickness via the
regulation of blood coagulation factors related to lipid metabolites in rats fed
a HFD.
PMID- 28413316
TI - Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting
TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2.
AB - BACKGROUND: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type
saponins isolated from Panax ginseng, a well-known medicinal herb with many
beneficial properties including anticancer, anti-inflammatory, antiobesity, and
antidiabetic effects. In this study, we investigated the effects of G-Rc on
inflammatory responses in vitro and examined the mechanisms of these effects.
METHODS: The in vitro inflammation system used lipopolysaccharide-treated
macrophages, tumor necrosis factor-alpha/interferon-gamma-treated synovial cells,
and HEK293 cells transfected with various inducers of inflammation. RESULTS: G-Rc
significantly inhibited the expression of macrophage-derived cytokines, such as
tumor necrosis factor-alpha and interleukin-1beta. G-Rc also markedly suppressed
the activation of TANK-binding kinase 1/IkappaB kinase epsilon/interferon
regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages,
human synovial cells, and HEK293 cells. CONCLUSION: G-Rc exerts its anti
inflammatory actions by suppressing TANK-binding kinase 1/IkappaB kinase
epsilon/interferon regulatory factor-3 and p38/ATF-2 signaling.
PMID- 28413317
TI - Korean Red Ginseng improves atopic dermatitis-like skin lesions by suppressing
expression of proinflammatory cytokines and chemokines in vivo and in vitro.
AB - BACKGROUND: The prevalence of allergic inflammatory diseases such as atopic
dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and
complete recovery is difficult. Korean Red Ginseng, which is the heat-processed
root of Panax ginseng Meyer, is widely and frequently used as a traditional
medicine in East Asia. In this study, we investigated whether Korean Red Ginseng
water extract (RGE) regulates the expression of proinflammatory cytokines and
chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa
B (NF-kappaB) pathway in allergic inflammation. METHODS: Compound 48/80-induced
anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin
lesion mice models were used to investigate the antiallergic effects of RGE.
Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to
clarify the effects of RGE on the expression of proinflammatory cytokines and
chemokines. RESULTS: Anaphylactic shock and DNFB-induced AD-like skin lesions
were attenuated by RGE administration through reduction of serum immunoglobulin E
(IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the
production of proinflammatory cytokines including IL-1beta, IL-6, and IL-8, and
expression of chemokines such as IL-8, thymus and activation-regulated chemokine
(TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE
decreased the release of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6,
and IL-8 as well as expressions of chemokines including macrophage inflammatory
protein (MIP)-1alpha, MIP-1beta, regulated on activation, normal T cell expressed
and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC
1 cells. Furthermore, our data demonstrated that these inhibitory effects
occurred through blockage of the MAPK and NF-kappaB pathway. CONCLUSION: RGE may
be a useful therapeutic agent for the treatment of allergic inflammatory diseases
such as AD-like dermatitis.
PMID- 28413318
TI - Genetic defects in the nef gene are associated with Korean Red Ginseng intake:
monitoring of nef sequence polymorphisms over 20 years.
AB - BACKGROUND: The presence of gross deletions in the human immunodeficiency virus
nef gene (gDeltanef) is associated with long-term nonprogression of infected
patients. Here, we investigated how quickly genetic defects in the nef gene are
associated with Korean Red Ginseng (KRG) intake in 10 long-term slow progressors.
METHODS: This study was divided into three phases over a 20-yr period; baseline,
KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef
gene amplicons were obtained using reverse transcription polymerase chain
reaction (PCR) and nested PCR from 10 long-term slow progressors (n = 1,396), and
nested PCR from 36 control patients (n = 198), and 28 ART patients (n = 157), and
these were then sequenced. The proportion of gDeltanef, premature stop codons,
and not in-frame insertion or deletion of a nucleotide was compared between three
phases, control, and ART patients. RESULTS: The proportion of defective nef genes
was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%),
control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p <
0.01). Small in-frame deletions or insertions were significantly more frequent
among patients treated with KRG alone compared with controls (p < 0.01).
Significantly fewer instances of genetic defects were detected in samples taken
during the KRG plus ART phase (7.8%; p < 0.01). The earliest defects detected
were gDeltanef and small in-frame deletions after 7 mo and 67 mo of KRG intake,
respectively. CONCLUSION: KRG treatment might induce genetic defects in the nef
gene. This report provides new insight into the importance of genetic defects in
the pathogenesis of AIDS.
PMID- 28413319
TI - Black ginseng-enriched Chong-Myung-Tang extracts improve spatial learning
behavior in rats and elicit anti-inflammatory effects in vitro.
AB - BACKGROUND: Chong-Myung-Tang (CMT) extract is widely used in Korea as a
traditional herbal tonic for increasing memory capacity in high-school students
and also for numerous body ailments since centuries. The use of CMT to improve
the learning capacity has been attributed to various plant constituents,
especially black ginseng, in it. Therefore, in this study, we have first
investigated whether black ginseng-enriched CMT extracts affected spatial
learning using the Morris water maze (MWM) test. Their molecular mechanism of
action underlying improvement of learning and memory was examined in vitro.
METHODS: We used two types of black ginseng-enriched CMT extracts, designated as
CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning
behavior and their anti-inflammatory effects in BV2 microglial cells. RESULTS:
Our results show that both black ginseng-enriched CMT extracts improved the
learning behavior in scopolamine-induced impairment in the water maze test.
Moreover, these extracts also inhibited nitric oxide production in BV2 cells,
with significant suppression of expression of proinflammatory cytokines,
especially inducible nitric oxide synthase, cyclooxygenase-2, and interleukin
1beta. The protein expression of mitogen-activated protein kinase and nuclear
factor-kappaB pathway factors was also diminished by black ginseng-enriched CMT
extracts, indicating that it not only improves the memory impairment, but also
acts a potent anti-inflammatory agent for neuroinflammatory diseases. CONCLUSION:
Our research for the first time provides the scientific evidence that consumption
of black ginseng-enriched CMT extract as a brain tonic improves memory
impairment. Thus, our study results can be taken as a reference for future
neurobehavioral studies.
PMID- 28413320
TI - Panax ginseng Meyer prevents radiation-induced liver injury via modulation of
oxidative stress and apoptosis.
AB - BACKGROUND: Radiotherapy is one of the most important modalities in cancer
treatment; however, normal tissue damage is a serious concern. Drug development
for the protection or reduction of normal tissue damage is therefore a clinical
issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and
its corresponding mechanisms. METHODS: C56BL/6 mice were orally pretreated with
P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or
intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then
exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of
irradiation, the biological properties of hematoxicity, fat accumulation,
histopathology, oxidative stress, antioxidant activity, pro-inflammatory
cytokines, and apoptosis signals were examined in the hepatic tissue. RESULTS:
The irradiation markedly induced myelosuppression as determined by hematological
analysis of the peripheral blood. Steatohepatitis was induced by X-ray
irradiations, whereas pretreatment with PGE significantly attenuated it.
Oxidative stress was drastically increased, whereas antioxidant components were
depleted by irradiation. Irradiation also notably increased serum liver enzymes
and hepatic protein levels of pro-inflammatory cytokines. Those alterations were
markedly normalized by pretreatment with PGE. The degree of irradiation-induced
hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was
evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'
triphosphate nick-end labeling assay, western blotting, and gene expressions
analysis, particularly of apoptotic molecules. CONCLUSION: We suggest that PGE
could be applicable for use against radiation-induced liver injury, and its
corresponding mechanisms involve the modulation of oxidative stress, inflammatory
reactions, and apoptosis.
PMID- 28413322
TI - Improved antimicrobial effect of ginseng extract by heat transformation.
AB - BACKGROUND: The incidence of halitosis has a prevalence of 22-50% throughout the
world and is generally caused by anaerobic oral microorganisms, such as
Fusobacterium nucleatum, Clostridium perfringens, and Porphyromonas gingivalis.
Previous investigations on the structure-activity relationships of ginsenosides
have led to contrasting results. Particularly, the antibacterial activity of less
polar ginsenosides against halitosis-related bacteria has not been reported.
METHODS: Crude saponins extracted from the Panax quinquefolius leaf-stem (AGS)
were treated at 130 degrees C for 3 h to obtain heat-transformed saponins (HTS).
Five ginsenoside-enriched fractions (HTS-1, HTS-2, HTS-3, HTS-4, and HTS-5) and
less polar ginsenosides were separated by HP-20 resin absorption and HPLC, and
the antimicrobial activity and mechanism were investigated. RESULTS: HPLC with
diode-array detection analysis revealed that heat treatment induced an extensive
conversion of polar ginsenosides (-Rg1/Re, -Rc, -Rb2, and -Rd) to less polar
compounds (-Rg2, -Rg3, -Rg6, -F4, -Rg5, and -Rk1). The antimicrobial assays
showed that HTS, HTS-3, and HTS-4 were effective at inhibiting the growth of F.
nucleatum, C. perfringens, and P. gingivalis. Ginsenosides-Rg5 showed the best
antimicrobial activity against the three bacteria, with the lowest values of
minimum inhibitory concentration and minimum bactericidal concentration. One
major reason for this result is that less polar ginsenosides can more easily
damage membrane integrity. CONCLUSION: The results indicated that the less polar
ginsenoside-enriched fraction from heat transformation can be used as an
antibacterial agent to control halitosis.
PMID- 28413321
TI - The beneficial effect of ginsenosides extracted by pulsed electric field against
hydrogen peroxide-induced oxidative stress in HEK-293 cells.
AB - BACKGROUND: Ginsenosides are the main pharmacological components of Panax ginseng
root, which are thought to be primarily responsible for the suppressing effect on
oxidative stress. METHODS: 2,2-diphenyl-1-picrylhydrazyl radical scavenging
activity and oxygen radical absorption capacity were applied to evaluate the
antioxidant activities of the ginsenosides. Human embryonic kidney 293 (HEK-293)
cells were incubated with ginsenosides extracted by pulsed electric field (PEF)
and solvent cold soak extraction (SCSE) for 24 h and then the injury was induced
by 40MUM H2O2. The cell viability and surface morphology of HEK-293 cells were
studied using MTS assay and scanning electron microscopy, respectively. Dichloro
dihydro-fluorescein diacetate fluorescent probe assay was used to measure the
level of intracellular reactive oxygen species. The intracellular antioxidant
activities of ginsenosides were evaluated by cellular antioxidant activity assay
in HepG2 cells. RESULTS: The PEF extracts displayed the higher 2,2-diphenyl-1
picrylhydrazyl radical scavenging activity and stronger oxygen radical absorption
capacity (with an oxygen radical absorption capacity value of 14.48 +/- 4.04MUM
TE per MUg/mL). The HEK-293 cell model also suggested that the protective effect
of PEF extracts was dose-dependently greater than SCSE extracts. Dichloro-dihydro
fluorescein diacetate assay further proved that PEF extracts are more active (8%
higher than SCSE extracts) in reducing intracellular reactive oxygen species
accumulation. In addition, scanning electron microscopy images showed that the
HEK-293 cells, which were treated with PEF extracts, maintained more intact
surface morphology. Cellular antioxidant activity values indicated that
ginsenosides extracted by PEF had stronger cellular antioxidant activity than
SCSE ginsenosides extracts. CONCLUSION: The present study demonstrated the
antioxidative effect of ginsenosides extracted by PEF in vitro. Furthermore,
rather than SCSE, PEF may be more useful as an alternative extraction technique
for the extraction of ginsenosides with enhanced antioxidant activity.
PMID- 28413323
TI - Preventive effect of fermented black ginseng against cisplatin-induced
nephrotoxicity in rats.
AB - BACKGROUND: Fermented black ginseng (FBG) is processed ginseng by the repeated
heat treatment and fermentation of raw ginseng. The protective effect and
mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate
its therapeutic potential. METHODS: The free radical scavenging activity of FBG
was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the
protective effect against cisplatin-induced renal damage was tested in rats. FBG
was orally administered every day at a dose of 150 mg/kg body weight for 10 d,
and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body
weight) with 0.9% saline on the 4th d. RESULTS: The DPPH radical-scavenging
activity of FBG (IC50 = 384 MUg/mL) was stronger than that of raw ginseng. The
improved DPPH radical-scavenging activity was mediated by the generation phenolic
compounds. The decreased cell viability by cisplatin was recovered significantly
after treatment with FBG in a dose-dependent manner. Then, the protective effect
of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The
decreased creatinine clearance levels, which are a reliable marker for renal
dysfunction in cisplatin-treated rats, were reduced to the normal level after the
administration of FBG. Moreover, FBG showed protective effects against cisplatin
induced oxidative renal damage in rats through the inhibition of NF-kappaB/p65,
COX-2, and caspase-3 activation. CONCLUSION: These results collectively show that
the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating
oxidative stress, inflammation, and apoptosis.
PMID- 28413324
TI - Ginseng authenticity testing by measuring carbon, nitrogen, and sulfur stable
isotope compositions that differ based on cultivation land and organic fertilizer
type.
AB - BACKGROUND: The natural ratios of carbon (C), nitrogen (N), and sulfur (S) stable
isotopes can be varied in some specific living organisms owing to various
isotopic fractionation processes in nature. Therefore, the analysis of C, N, and
S stable isotope ratios in ginseng can provide a feasible method for determining
ginseng authenticity depending on the cultivation land and type of fertilizer.
METHODS: C, N, and S stable isotope composition in 6-yr-old ginseng roots
(Jagyeongjong variety) was measured by isotope ratio mass spectrometry. RESULTS:
The type of cultivation land and organic fertilizers affected the C, N, and S
stable isotope ratio in ginseng (p < 0.05). The delta15NAIR and delta34SVCDT
values in ginseng roots more significantly discriminated the cultivation land and
type of organic fertilizers in ginseng cultivation than the delta13CVPDB value.
The combination of delta13CVPDB, delta15NAIR, or delta34SVCDT in ginseng, except
the combination delta13CVPDB-34SVCDT, showed a better discrimination depending on
soil type or fertilizer type. CONCLUSION: This case study provides preliminary
results about the variation of C, N, and S isotope composition in ginseng
according to the cultivation soil type and organic fertilizer type. Hence, our
findings are potentially applicable to evaluate ginseng authenticity depending on
cultivation conditions.
PMID- 28413325
TI - The psychopharmacological activities of Vietnamese ginseng in mice:
characterization of its psychomotor, sedative-hypnotic, antistress, anxiolytic,
and cognitive effects.
AB - BACKGROUND: Panax vietnamensis Ha et Grushv. or Vietnamese ginseng (VG) is a
recently discovered ginseng species. Studies on its chemical constituents have
shown that VG is remarkably rich in ginseng saponins, particularly ocotillol
saponins. However, the psychopharmacological effects of VG have not been
characterized. Thus, in the present study we screened the psychopharmacological
activities of VG in mice. METHODS: VG extract (VGE) was orally administered to
mice at various dosages to evaluate its psychomotor (open-field and rota-rod
tests), sedative-hypnotic (pentobarbital-induced sleeping test), antistress (cold
swimming test), anxiolytic (elevated plus-maze test), and cognitive (Y-maze and
passive-avoidance tests) effects. RESULTS: VGE treatment increased the
spontaneous locomotor activity, enhanced the endurance to stress, reduced the
anxiety-like behavior, and ameliorated the scopolamine-induced memory impairments
in mice. In addition, VGE treatment did not alter the motor balance and
coordination of mice and did not potentiate pentobarbital-induced sleep,
indicating that VGE has no sedative-hypnotic effects. The effects of VGE were
comparable to those of the Korean Red Ginseng extract. CONCLUSION: VG, like other
ginseng products, has significant and potentially useful psychopharmacological
effects. This includes, but is not limited to, psychomotor stimulation,
anxiolytic, antistress, and memory enhancing effects.
PMID- 28413326
TI - Effect of B-complex vitamins on the antifatigue activity and bioavailability of
ginsenoside Re after oral administration.
AB - BACKGROUND: Both ginsenoside Re and B-complex vitamins are widely used as
nutritional supplements. They are often taken together so as to fully utilize
their antifatigue and refreshing effects, respectively. Whether actually a drug
nutrient interaction exists between ginsenoside Re and B-complex vitamins is
still unknown. The objective of this study was to simultaneously investigate the
effect of B-complex vitamins on the antifatigue activity and bioavailability of
ginsenoside Re after their oral administration. The study results will provide
valuable theoretical guidance for the combined utilization of ginseng and B
complex vitamins. METHODS: Ginsenoside Re with or without B-complex vitamins was
orally administered to mice to evaluate its antifatigue effects and to rats to
evaluate its bioavailability. The antifatigue activity was evaluated by the
weight-loaded swimming test and biochemical parameters, including hepatic
glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of
ginsenoside Re in plasma was determined by liquid chromatography-tandem mass
spectrometry. RESULTS: No antifatigue effect of ginsenoside Re was noted when
ginsenoside Re in combination with B-complex vitamins was orally administered to
mice. B-complex vitamins caused to a reduction in the bioavailability of
ginsenoside Re with the area under the concentration-time curve from zero to
infinity markedly decreasing from 11,830.85 +/- 2,366.47 h.ng/mL to 890.55 +/-
372.94 h.ng/mL. CONCLUSION: The results suggested that there were pharmacokinetic
and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B
complex vitamins. B-complex vitamins can significantly weaken the antifatigue
effect and decrease the bioavailability of ginsenoside Re when simultaneously
administered orally.
PMID- 28413328
TI - Effect of Korean Red Ginseng intake on the survival duration of human
immunodeficiency virus type 1 patients.
AB - BACKGROUND: Long-term ginseng intake can increase longevity in healthy
individuals. Here, we examined if long-term treatment with Panax ginseng Meyer
(Korean Red Ginseng, KRG) can also enhance survival duration (SD) in patients
with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We
retrospectively analyzed 252 HIV-1 patients diagnosed from 1986 to 2013 prior to
the initiation of antiretroviral therapy. Overall, 162 patients were treated with
KRG (3,947 +/- 4,943 g) for 86 +/- 63 mo. The effects of KRG on SD were analyzed
according to the KRG intake level and the length of the follow-up period.
RESULTS: There were significant correlations between the total amount of KRG and
SD in the KRG intake group (r = 0.64, p < 0.0001) as well as between total amount
of KRG and mean annual decrease in CD4+ T-cell count in all 252 patients (r =
0.17, p < 0.01). The annual decrease in CD4+ T-cell count (change in cells/MUL)
was significantly slower in KRG-treated patients than in patients receiving no
KRG (48 +/- 40 vs. 106 +/- 162; p < 0.001). The SD (in months) was also
significantly longer in the KRG group than in the no-KRG group (101 +/- 64 vs. 59
+/- 40, p < 0.01). CONCLUSION: KRG prolongs survival in HIV-1 patients, possibly
by slowing the decrease in CD4+ T-cell count.
PMID- 28413327
TI - Effects of ginseng on two main sex steroid hormone receptors: estrogen and
androgen receptors.
AB - Ginseng has been used in China for at least two millennia and is now popular in
over 35 countries. It is one of the world's popular herbs for complementary and
alternative medicine and has been shown to have helpful effects on cognition and
blood circulation, as well as anti-aging, anti-cancer, and anti-diabetic effects,
among many others. The pharmacological activities of ginseng are dependent mainly
on ginsenosides. Ginsenosides have a cholesterol-like four trans-ring steroid
skeleton with a variety of sugar moieties. Nuclear receptors are one of the most
important molecular targets of ginseng, and reports have shown that members of
the nuclear receptor superfamily are regulated by a variety of ginsenosides.
Here, we review the published literature on the effects of ginseng and its
constituents on two main sex steroid hormone receptors: estrogen and androgen
receptors. Furthermore, we discuss applications for sex steroid hormone receptor
modulation and their therapeutic efficacy.
PMID- 28413329
TI - Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in
LLC-PK1 kidney cells.
AB - BACKGROUND: Ginsenosides are active components of Panax ginseng that exert
various health benefits including kidney protection effect. The medicinal
activity of ginsenosides can be enhanced by modulating their stereospecificity by
heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the
double bond at C-20(21) or C-20(22). METHODS: The present study investigated the
kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a
platinum based anticancer drug, induced apoptotic damage in renal proximal LLC
PK1 cells. RESULTS: As a result, ginsenoside Rh3 shows a stronger protective
effect than that shown by Rk2. Cisplatin-induced elevated protein levels of
phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated
kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with
ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells
induced by cisplatin treatment also significantly reduced after cotreatment with
ginsenoside Rh3. CONCLUSION: These results demonstrate that inhibition of the JNK
and ERK mitogen-activated protein kinase signaling cascade plays a critical role
in mediating the renoprotective effect of ginsenoside Rh3.
PMID- 28413331
TI - A laboratory study of nonlinear changes in the directionality of extreme seas.
AB - This paper concerns the description of surface water waves, specifically
nonlinear changes in the directionality. Supporting calculations are provided to
establish the best method of directional wave generation, the preferred method of
directional analysis and the inputs on which such a method should be based. These
calculations show that a random directional method, in which the phasing,
amplitude and direction of propagation of individual wave components are chosen
randomly, has benefits in achieving the required ergodicity. In terms of analysis
procedures, the extended maximum entropy principle, with inputs based upon vector
quantities, produces the best description of directionality. With laboratory data
describing the water surface elevation and the two horizontal velocity components
at a single point, several steep sea states are considered. The results confirm
that, as the steepness of a sea state increases, the overall directionality of
the sea state reduces. More importantly, it is also shown that the largest waves
become less spread or more unidirectional than the sea state as a whole. This
provides an important link to earlier descriptions of deterministic wave groups
produced by frequency focusing, helps to explain recent field observations and
has important practical implications for the design of marine structures and
vessels.
PMID- 28413332
TI - Fluid dynamics of acoustic and hydrodynamic cavitation in hydraulic power
systems.
AB - Cavitation is the transition from a liquid to a vapour phase, due to a drop in
pressure to the level of the vapour tension of the fluid. Two kinds of cavitation
have been reviewed here: acoustic cavitation and hydrodynamic cavitation. As
acoustic cavitation in engineering systems is related to the propagation of waves
through a region subjected to liquid vaporization, the available expressions of
the sound speed are discussed. One of the main effects of hydrodynamic cavitation
in the nozzles and orifices of hydraulic power systems is a reduction in flow
permeability. Different discharge coefficient formulae are analysed in this
paper: the Reynolds number and the cavitation number result to be the key fluid
dynamical parameters for liquid and cavitating flows, respectively. The latest
advances in the characterization of different cavitation regimes in a nozzle, as
the cavitation number reduces, are presented. The physical cause of choked flows
is explained, and an analogy between cavitation and supersonic aerodynamic flows
is proposed. The main approaches to cavitation modelling in hydraulic power
systems are also reviewed: these are divided into homogeneous-mixture and two
phase models. The homogeneous-mixture models are further subdivided into
barotropic and baroclinic models. The advantages and disadvantages of an
implementation of the complete Rayleigh-Plesset equation are examined.
PMID- 28413333
TI - Equilibrium shapes of a heterogeneous bubble in an electric field: a variational
formulation and numerical verifications.
AB - The equilibrium shape of a bubble/droplet in an electric field is important for
electrowetting over dielectrics (EWOD), electrohydrodynamic (EHD) enhancement for
heat transfer and electro-deformation of a single biological cell among others.
In this work, we develop a general variational formulation in account of electro
mechanical couplings. In the context of EHD, we identify the free energy
functional and the associated energy minimization problem that determines the
equilibrium shape of a bubble in an electric field. Based on this variational
formulation, we implement a fixed mesh level-set gradient method for computing
the equilibrium shapes. This numerical scheme is efficient and validated by
comparing with analytical solutions at the absence of electric field and
experimental results at the presence of electric field. We also present
simulation results for zero gravity which will be useful for space applications.
The variational formulation and numerical scheme are anticipated to have broad
applications in areas of EWOD, EHD and electro-deformation in biomechanics.
PMID- 28413330
TI - Toxoplasmosis seroprevalence in Iranian women and risk factors of the disease: a
systematic review and meta-analysis.
AB - BACKGROUND: Toxoplasmosis is caused by an intracellular obligatory parasite,
Toxoplasma gondii, and it has global distribution. The purposes of this
systematic review and meta-analysis were to evaluate the seroprevalence of
toxoplasmosis in Iranian pregnant women, and girls and women of childbearing age,
and identify potentially preventable risk factors. METHODS: Between November 2014
and February 2017, nine electronic databases that reported data on the T. gondii
seroprevalence in Iranian women were searched. Our search resulted in 83 reports
published from 1994 to 2017. RESULTS: The results showed that the pooled
estimation for the prevalence of T. gondii using a random-effect model was 43%
(95% confidence interval (CI) = 38-48%) in pregnant women and 33% (95% CI = 23
43%) in girls and the childbearing age groups. There was a significant
association between the T. gondii seroprevalence with age and the gestational age
of conception in pregnant women and those who had contact with cats in both
groups. CONCLUSIONS: This is the first comprehensive systematic review of T.
gondii infection seroprevalence in Iranian women, which showed a high prevalence
of Toxoplasma infection. Around 57% of pregnant women and 67% of girls and the
childbearing age groups were seronegative and thus were susceptible to infection
and should be monitored.
PMID- 28413334
TI - Landslides and tsunamis predicted by incompressible smoothed particle
hydrodynamics (SPH) with application to the 1958 Lituya Bay event and idealized
experiment.
AB - Tsunamis caused by landslides may result in significant destruction of the
surroundings with both societal and industrial impact. The 1958 Lituya Bay
landslide and tsunami is a recent and well-documented terrestrial landslide
generating a tsunami with a run-up of 524 m. Although recent computational
techniques have shown good performance in the estimation of the run-up height,
they fail to capture all the physical processes, in particular, the landslide
entry profile and interaction with the water. Smoothed particle hydrodynamics
(SPH) is a versatile numerical technique for describing free-surface and multi
phase flows, particularly those that exhibit highly nonlinear deformation in
landslide-generated tsunamis. In the current work, the novel multi-phase
incompressible SPH method with shifting is applied to the Lituya Bay tsunami and
landslide and is the first methodology able to reproduce realistically both the
run-up and landslide-entry as documented in a benchmark experiment. The method is
the first paper to develop a realistic implementation of the physics that in
addition to the non-Newtonian rheology of the landslide includes turbulence in
the water phase and soil saturation. Sensitivity to the experimental initial
conditions is also considered. This work demonstrates the ability of the proposed
method in modelling challenging environmental multi-phase, non-Newtonian and
turbulent flows.
PMID- 28413335
TI - Superregular breathers, characteristics of nonlinear stage of modulation
instability induced by higher-order effects.
AB - We study the higher-order generalized nonlinear Schrodinger (NLS) equation
describing the propagation of ultrashort optical pulse in optical fibres. By
using Darboux transformation, we derive the superregular breather solution that
develops from a small localized perturbation. This type of solution can be used
to characterize the nonlinear stage of the modulation instability (MI) of the
condensate. In particular, we show some novel characteristics of the nonlinear
stage of MI arising from higher-order effects: (i) coexistence of a quasi
Akhmediev breather and a multipeak soliton; (ii) two multipeak solitons
propagation in opposite directions; (iii) a beating pattern followed by two
multipeak solitons in the same direction. It is found that these patterns
generated from a small localized perturbation do not have the analogues in the
standard NLS equation. Our results enrich Zakharov's theory of superregular
breathers and could provide helpful insight on the nonlinear stage of MI in
presence of the higher-order effects.
PMID- 28413336
TI - A restatement of the natural science evidence concerning catchment-based
'natural' flood management in the UK.
AB - Flooding is a very costly natural hazard in the UK and is expected to increase
further under future climate change scenarios. Flood defences are commonly
deployed to protect communities and property from flooding, but in recent years
flood management policy has looked towards solutions that seek to mitigate flood
risk at flood-prone sites through targeted interventions throughout the
catchment, sometimes using techniques which involve working with natural
processes. This paper describes a project to provide a succinct summary of the
natural science evidence base concerning the effectiveness of catchment-based
'natural' flood management in the UK. The evidence summary is designed to be read
by an informed but not technically specialist audience. Each evidence statement
is placed into one of four categories describing the nature of the underlying
information. The evidence summary forms the appendix to this paper and an
annotated bibliography is provided in the electronic supplementary material.
PMID- 28413337
TI - Device-independent tests of quantum channels.
AB - We develop a device-independent framework for testing quantum channels. That is,
we falsify a hypothesis about a quantum channel based only on an observed set of
input-output correlations. Formally, the problem consists of characterizing the
set of input-output correlations compatible with any arbitrary given quantum
channel. For binary (i.e. two input symbols, two output symbols) correlations, we
show that extremal correlations are always achieved by orthogonal encodings and
measurements, irrespective of whether or not the channel preserves commutativity.
We further provide a full, closed-form characterization of the sets of binary
correlations in the case of: (i) any dihedrally covariant qubit channel (such as
any Pauli and amplitude-damping channels) and (ii) any universally-covariant
commutativity-preserving channel in an arbitrary dimension (such as any erasure,
depolarizing, universal cloning and universal transposition channels).
PMID- 28413338
TI - The cross-over to magnetostrophic convection in planetary dynamo systems.
AB - Global scale magnetostrophic balance, in which Lorentz and Coriolis forces
comprise the leading-order force balance, has long been thought to describe the
natural state of planetary dynamo systems. This argument arises from
consideration of the linear theory of rotating magnetoconvection. Here we test
this long-held tenet by directly comparing linear predictions against dynamo
modelling results. This comparison shows that dynamo modelling results are not
typically in the global magnetostrophic state predicted by linear theory. Then,
in order to estimate at what scale (if any) magnetostrophic balance will arise in
nonlinear dynamo systems, we carry out a simple scaling analysis of the Elsasser
number Lambda, yielding an improved estimate of the ratio of Lorentz and Coriolis
forces. From this, we deduce that there is a magnetostrophic cross-over length
scale, [Formula: see text], where Lambdao is the linear (or traditional) Elsasser
number, Rmo is the system scale magnetic Reynolds number and D is the length
scale of the system. On scales well above [Formula: see text], magnetostrophic
convection dynamics should not be possible. Only on scales smaller than [Formula:
see text] should it be possible for the convective behaviours to follow the
predictions for the magnetostrophic branch of convection. Because [Formula: see
text] is significantly smaller than the system scale in most dynamo models, their
large-scale flows should be quasi-geostrophic, as is confirmed in many dynamo
simulations. Estimating Lambdao ?1 and Rmo ?103 in Earth's core, the cross-over
scale is approximately 1/1000 that of the system scale, suggesting that
magnetostrophic convection dynamics exists in the core only on small scales below
those that can be characterized by geomagnetic observations.
PMID- 28413339
TI - Efficient generation of receiver operating characteristics for the evaluation of
damage detection in practical structural health monitoring applications.
AB - Permanently installed guided wave monitoring systems are attractive for
monitoring large structures. By frequently interrogating the test structure over
a long period of time, such systems have the potential to detect defects much
earlier than with conventional one-off inspection, and reduce the time and labour
cost involved. However, for the systems to be accepted under real operational
conditions, their damage detection performance needs to be evaluated in these
practical settings. The receiver operating characteristic (ROC) is an established
performance metric for one-off inspections, but the generation of the ROC
requires many test structures with realistic damage growth at different locations
and different environmental conditions, and this is often impractical. In this
paper, we propose an evaluation framework using experimental data collected over
multiple environmental cycles on an undamaged structure with synthetic damage
signatures added by superposition. Recent advances in computation power enable
examples covering a wide range of practical scenarios to be generated, and for
multiple cases of each scenario to be tested so that the statistics of the
performance can be evaluated. The proposed methodology has been demonstrated
using data collected from a laboratory pipe specimen over many temperature
cycles, superposed with damage signatures predicted for a flat-bottom hole
growing at different rates at various locations. Three damage detection schemes,
conventional baseline subtraction, singular value decomposition (SVD) and
independent component analysis (ICA), have been evaluated. It has been shown that
in all cases, the component methods perform significantly better than the
residual method, with ICA generally the better of the two. The results have been
validated using experimental data monitoring a pipe in which a flat-bottom hole
was drilled and enlarged over successive temperature cycles. The methodology can
be used to evaluate the performance of an installed monitoring system and to show
whether it is capable of detecting particular damage growth at any given
location. It will enable monitoring results to be evaluated rigorously and will
be valuable in the development of safety cases.
PMID- 28413340
TI - History dependence and the continuum approximation breakdown: the impact of
domain growth on Turing's instability.
AB - A diffusively driven instability has been hypothesized as a mechanism to drive
spatial self-organization in biological systems since the seminal work of Turing.
Such systems are often considered on a growing domain, but traditional
theoretical studies have only treated the domain size as a bifurcation parameter,
neglecting the system non-autonomy. More recently, the conditions for a
diffusively driven instability on a growing domain have been determined under
stringent conditions, including slow growth, a restriction on the temporal
interval over which the prospect of an instability can be considered and a
neglect of the impact that time evolution has on the stability properties of the
homogeneous reference state from which heterogeneity emerges. Here, we firstly
relax this latter assumption and observe that the conditions for the Turing
instability are much more complex and depend on the history of the system in
general. We proceed to relax all the above constraints, making analytical
progress by focusing on specific examples. With faster growth, instabilities can
grow transiently and decay, making the prediction of a prospective Turing
instability much more difficult. In addition, arbitrarily high spatial
frequencies can destabilize, in which case the continuum approximation is
predicted to break down.
PMID- 28413341
TI - SPARSE-A subgrid particle averaged Reynolds stress equivalent model: testing with
a priori closure.
AB - A Lagrangian particle cloud model is proposed that accounts for the effects of
Reynolds-averaged particle and turbulent stresses and the averaged carrier-phase
velocity of the subparticle cloud scale on the averaged motion and velocity of
the cloud. The SPARSE (subgrid particle averaged Reynolds stress equivalent)
model is based on a combination of a truncated Taylor expansion of a drag
correction function and Reynolds averaging. It reduces the required number of
computational parcels to trace a cloud of particles in Eulerian-Lagrangian
methods for the simulation of particle-laden flow. Closure is performed in an a
priori manner using a reference simulation where all particles in the cloud are
traced individually with a point-particle model. Comparison of a first-order
model and SPARSE with the reference simulation in one dimension shows that both
the stress and the averaging of the carrier-phase velocity on the cloud subscale
affect the averaged motion of the particle. A three-dimensional isotropic
turbulence computation shows that only one computational parcel is sufficient to
accurately trace a cloud of tens of thousands of particles.
PMID- 28413342
TI - Identifying the significance of nonlinear normal modes.
AB - Nonlinear normal modes (NNMs) are widely used as a tool for understanding the
forced responses of nonlinear systems. However, the contemporary definition of an
NNM also encompasses a large number of dynamic behaviours which are not observed
when a system is forced and damped. As such, only a few NNMs are required to
understand the forced dynamics. This paper firstly demonstrates the complexity
that may arise from the NNMs of a simple nonlinear system-highlighting the need
for a method for identifying the significance of NNMs. An analytical
investigation is used, alongside energy arguments, to develop an understanding of
the mechanisms that relate the NNMs to the forced responses. This provides
insight into which NNMs are pertinent to understanding the forced dynamics, and
which may be disregarded. The NNMs are compared with simulated forced responses
to verify these findings.
PMID- 28413343
TI - G-Strands on symmetric spaces.
AB - We study the G-strand equations that are extensions of the classical chiral model
of particle physics in the particular setting of broken symmetries described by
symmetric spaces. These equations are simple field theory models whose
configuration space is a Lie group, or in this case a symmetric space. In this
class of systems, we derive several models that are completely integrable on
finite dimensional Lie group G, and we treat in more detail examples with
symmetric space SU(2)/S1 and SO(4)/SO(3). The latter model simplifies to an
apparently new integrable nine-dimensional system. We also study the G-strands on
the infinite dimensional group of diffeomorphisms, which gives, together with the
Sobolev norm, systems of 1+2 Camassa-Holm equations. The solutions of these
equations on the complementary space related to the Witt algebra decomposition
are the odd function solutions.
PMID- 28413344
TI - Analytical results regarding electrostatic resonances of surface phonon/plasmon
polaritons: separation of variables with a twist.
AB - The boundary integral equation (BIE) method ascertains explicit relations between
localized surface phonon and plasmon polariton resonances and the eigenvalues of
its associated electrostatic operator. We show that group-theoretical analysis of
the Laplace equation can be used to calculate the full set of eigenvalues and
eigenfunctions of the electrostatic operator for shapes and shells described by
separable coordinate systems. These results not only unify and generalize many
existing studies, but also offer us the opportunity to expand the study of
phenomena such as cloaking by anomalous localized resonance. Hence, we calculate
the eigenvalues and eigenfunctions of elliptic and circular cylinders. We
illustrate the benefits of using the BIE method to interpret recent experiments
involving localized surface phonon polariton resonances and the size scaling of
plasmon resonances in graphene nanodiscs. Finally, symmetry-based operator
analysis can be extended from the electrostatic to the full-wave regime. Thus,
bound states of light in the continuum can be studied for shapes beyond spherical
configurations.
PMID- 28413345
TI - Modelling damped acoustic waves by a dissipation-preserving conformal symplectic
method.
AB - We propose a novel stable and efficient dissipation-preserving method for
acoustic wave propagations in attenuating media with both correct phase and
amplitude. Through introducing the conformal multi-symplectic structure, the
intrinsic dissipation law and the conformal symplectic conservation law are
revealed for the damped acoustic wave equation. The proposed algorithm is exactly
designed to preserve a discrete version of the conformal symplectic conservation
law. More specifically, two subsystems in conjunction with the original damped
wave equation are derived. One is actually the conservative Hamiltonian wave
equation and the other is a dissipative linear ordinary differential equation
(ODE) system. Standard symplectic method is devoted to the conservative system,
whereas the analytical solution is obtained for the ODE system. An explicit
conformal symplectic scheme is constructed by concatenating these two parts of
solutions by the Strang splitting technique. Stability analysis and convergence
tests are given thereafter. A benchmark model in homogeneous media is presented
to demonstrate the effectiveness and advantage of our method in suppressing
numerical dispersion and preserving the energy dissipation. Further numerical
tests show that our proposed method can efficiently capture the dissipation in
heterogeneous media.
PMID- 28413346
TI - Rapidly convergent quasi-periodic Green functions for scattering by arrays of
cylinders-including Wood anomalies.
AB - This paper presents a full-spectrum Green-function methodology (which is valid,
in particular, at and around Wood-anomaly frequencies) for evaluation of
scattering by periodic arrays of cylinders of arbitrary cross section-with
application to wire gratings, particle arrays and reflectarrays and, indeed,
general arrays of conducting or dielectric bounded obstacles under both
transverse electric and transverse magnetic polarized illumination. The proposed
method, which, for definiteness, is demonstrated here for arrays of perfectly
conducting particles under transverse electric polarization, is based on the use
of the shifted Green-function method introduced in a recent contribution (Bruno &
Delourme 2014 J. Computat. Phys.262, 262-290 (doi:10.1016/j.jcp.2013.12.047)). A
certain infinite term arises at Wood anomalies for the cylinder-array problems
considered here that is not present in the previous rough-surface case. As shown
in this paper, these infinite terms can be treated via an application of ideas
related to the Woodbury-Sherman-Morrison formulae. The resulting approach, which
is applicable to general arrays of obstacles even at and around Wood-anomaly
frequencies, exhibits fast convergence and high accuracies. For example, a few
hundreds of milliseconds suffice for the proposed approach to evaluate solutions
throughout the resonance region (wavelengths comparable to the period and
cylinder sizes) with full single-precision accuracy.
PMID- 28413347
TI - A biochemo-mechano coupled, computational model combining membrane transport and
pericellular proteolysis in tissue mechanics.
AB - We present a computational model for the interaction of surface- and volume-bound
scalar transport and reaction processes with a deformable porous medium. The
application in mind is pericellular proteolysis, i.e. the dissolution of the
solid phase of the extracellular matrix (ECM) as a response to the activation of
certain chemical species at the cell membrane and in the vicinity of the cell. A
poroelastic medium model represents the extra cellular scaffold and the
interstitial fluid flow, while a surface-bound transport model accounts for the
diffusion and reaction of membrane-bound chemical species. By further modelling
the volume-bound transport, we consider the advection, diffusion and reaction of
sequestered chemical species within the extracellular scaffold. The chemo
mechanical coupling is established by introducing a continuum formulation for the
interplay of reaction rates and the mechanical state of the ECM. It is based on
known experimental insights and theoretical work on the thermodynamics of porous
media and degradation kinetics of collagen fibres on the one hand and a damage
like effect of the fibre dissolution on the mechanical integrity of the ECM on
the other hand. The resulting system of partial differential equations is solved
via the finite-element method. To the best of our knowledge, it is the first
computational model including contemporaneously the coupling between (i)
advection-diffusion-reaction processes, (ii) interstitial flow and deformation of
a porous medium, and (iii) the chemo-mechanical interaction impelled by the
dissolution of the ECM. Our numerical examples show good agreement with
experimental data. Furthermore, we outline the capability of the methodology to
extend existing numerical approaches towards a more comprehensive model for
cellular biochemo-mechanics.
PMID- 28413348
TI - Biofriendly nanocomposite containers with inhibition properties for the
protection of metallic surfaces.
AB - An attempt to combine two 'green' compounds in nanocomposite microcontainers in
order to increase protection properties of waterborne acryl-styrene copolymer
(ASC) coatings has been made. N-lauroylsarcosine (NLS) served as a corrosion
inhibitor, and linseed oil (LO) as a carrier-forming component. LO is compatible
with this copolymer and can impart to the coating self-healing properties. For
the evaluation of the protective performance, three types of coatings were
compared. In the first two, NLS was introduced in the coating formulation in the
forms of free powder and micro-containers filled with LO, correspondingly. The
last one was a standard ASC coating without inhibitor at all. Low-carbon steel
substrates were coated by these formulations by spraying and subjected
subsequently to the neutral salt spray test according to DIN ISO 9227. Results of
these tests as well as the data obtained by electrochemical study suggest that
such containers can be used for the improvement of adhesion of ASC-based coatings
to the substrate and for the enhancement of their protective performance upon
integrity damage, whereas the barrier properties of intact coatings were
decreased.
PMID- 28413349
TI - Comment on 'Are some people suffering as a result of increasing mass exposure of
the public to ultrasound in air?'
AB - A number of queries regarding the paper 'Are some people suffering as a result of
increasing mass exposure of the public to ultrasound in air?' (Leighton 2016
Proc. R. Soc. A472, 20150624 (doi:10.1098/rspa.2015.0624)) have been sent in from
readers, almost all based around some or all of a small set of questions. These
can be grouped into issues of engineering, human factors and timeliness. Those
issues (represented by the most typical wording used in queries) and my responses
are summarized in this comment.
PMID- 28413351
TI - Emerging surface characterization techniques for carbon steel corrosion: a
critical brief review.
AB - Carbon steel is a preferred construction material in many industrial and domestic
applications, including oil and gas pipelines, where corrosion mitigation using
film-forming corrosion inhibitor formulations is a widely accepted method. This
review identifies surface analytical techniques that are considered suitable for
analysis of thin films at metallic substrates, but are yet to be applied to
analysis of carbon steel surfaces in corrosive media or treated with corrosion
inhibitors. The reviewed methods include time of flight-secondary ion mass
spectrometry, X-ray absorption spectroscopy methods, particle-induced X-ray
emission, Rutherford backscatter spectroscopy, Auger electron spectroscopy,
electron probe microanalysis, near-edge X-ray absorption fine structure
spectroscopy, X-ray photoemission electron microscopy, low-energy electron
diffraction, small-angle neutron scattering and neutron reflectometry, and
conversion electron Moessbauer spectrometry. Advantages and limitations of the
analytical methods in thin-film surface investigations are discussed. Technical
parameters of nominated analytical methods are provided to assist in the
selection of suitable methods for analysis of metallic substrates deposited with
surface films. The challenges associated with the applications of the emerging
analytical methods in corrosion science are also addressed.
PMID- 28413350
TI - Mechanics of ultrasound elastography.
AB - Ultrasound elastography enables in vivo measurement of the mechanical properties
of living soft tissues in a non-destructive and non-invasive manner and has
attracted considerable interest for clinical use in recent years. Continuum
mechanics plays an essential role in understanding and improving ultrasound-based
elastography methods and is the main focus of this review. In particular, the
mechanics theories involved in both static and dynamic elastography methods are
surveyed. They may help understand the challenges in and opportunities for the
practical applications of various ultrasound elastography methods to characterize
the linear elastic, viscoelastic, anisotropic elastic and hyperelastic properties
of both bulk and thin-walled soft materials, especially the in vivo
characterization of biological soft tissues.
PMID- 28413352
TI - The Fourier decomposition method for nonlinear and non-stationary time series
analysis.
AB - for many decades, there has been a general perception in the literature that
Fourier methods are not suitable for the analysis of nonlinear and non-stationary
data. In this paper, we propose a novel and adaptive Fourier decomposition method
(FDM), based on the Fourier theory, and demonstrate its efficacy for the analysis
of nonlinear and non-stationary time series. The proposed FDM decomposes any data
into a small number of 'Fourier intrinsic band functions' (FIBFs). The FDM
presents a generalized Fourier expansion with variable amplitudes and variable
frequencies of a time series by the Fourier method itself. We propose an idea of
zero-phase filter bank-based multivariate FDM (MFDM), for the analysis of
multivariate nonlinear and non-stationary time series, using the FDM. We also
present an algorithm to obtain cut-off frequencies for MFDM. The proposed MFDM
generates a finite number of band-limited multivariate FIBFs (MFIBFs). The MFDM
preserves some intrinsic physical properties of the multivariate data, such as
scale alignment, trend and instantaneous frequency. The proposed methods provide
a time-frequency-energy (TFE) distribution that reveals the intrinsic structure
of a data. Numerical computations and simulations have been carried out and
comparison is made with the empirical mode decomposition algorithms.
PMID- 28413353
TI - Microprocessors: the engines of the digital age.
AB - The microprocessor-a computer central processing unit integrated onto a single
microchip-has come to dominate computing across all of its scales from the
tiniest consumer appliance to the largest supercomputer. This dominance has taken
decades to achieve, but an irresistible logic made the ultimate outcome
inevitable. The objectives of this Perspective paper are to offer a brief history
of the development of the microprocessor and to answer questions such as: where
did the microprocessor come from, where is it now, and where might it go in the
future?
PMID- 28413354
TI - Resistive-pulse and rectification sensing with glass and carbon nanopipettes.
AB - Along with more prevalent solid-state nanopores, glass or quartz nanopipettes
have found applications in resistive-pulse and rectification sensing. Their
advantages include the ease of fabrication, small physical size and needle-like
geometry, rendering them useful for local measurements in small spaces and
delivery of nanoparticles/biomolecules. Carbon nanopipettes fabricated by
depositing a thin carbon layer on the inner wall of a quartz pipette provide
additional means for detecting electroactive species and fine-tuning the current
rectification properties. In this paper, we discuss the fundamentals of resistive
pulse sensing with nanopipettes and our recent studies of current rectification
in carbon pipettes.
PMID- 28413355
TI - A computational continuum model of poroelastic beds.
AB - Despite the ubiquity of fluid flows interacting with porous and elastic
materials, we lack a validated non-empirical macroscale method for characterizing
the flow over and through a poroelastic medium. We propose a computational tool
to describe such configurations by deriving and validating a continuum model for
the poroelastic bed and its interface with the above free fluid. We show that,
using stress continuity condition and slip velocity condition at the interface,
the effective model captures the effects of small changes in the microstructure
anisotropy correctly and predicts the overall behaviour in a physically
consistent and controllable manner. Moreover, we show that the performance of the
effective model is accurate by validating with fully microscopic resolved
simulations. The proposed computational tool can be used in investigations in a
wide range of fields, including mechanical engineering, bio-engineering and
geophysics.
PMID- 28413356
TI - Propagation of combustion waves in the shell-core energetic materials with
external heat losses.
AB - In this paper, the properties and stability of combustion waves propagating in
the composite solid energetic material of the shell-core type are numerically
investigated within the one-dimensional diffusive-thermal model with heat losses
to the surroundings. The flame speed is calculated as a function of the
parameters of the model. The boundaries of stability are determined in the space
of parameters by solving the linear stability problem and direct integration of
the governing non-stationary equations. The results are compared with the
characteristics of the combustion waves in pure solid fuel. It is demonstrated
that a stable travelling combustion wave solution can exist for the parameters of
the model for which the flame front propagation is unstable in pure solid fuel
and it can propagate several times faster even in the presence of significant
heat losses.
PMID- 28413357
TI - Introduction for perspectives in geophysical and astrophysical fluids.
PMID- 28413358
TI - The soft computing-based approach to investigate allergic diseases: a systematic
review.
AB - BACKGROUND: Early recognition of inflammatory markers and their relation to
asthma, adverse drug reactions, allergic rhinitis, atopic dermatitis and other
allergic diseases is an important goal in allergy. The vast majority of studies
in the literature are based on classic statistical methods; however, developments
in computational techniques such as soft computing-based approaches hold new
promise in this field. OBJECTIVE: The aim of this manuscript is to systematically
review the main soft computing-based techniques such as artificial neural
networks, support vector machines, bayesian networks and fuzzy logic to
investigate their performances in the field of allergic diseases. METHODS: The
review was conducted following PRISMA guidelines and the protocol was registered
within PROSPERO database (CRD42016038894). The research was performed on PubMed
and ScienceDirect, covering the period starting from September 1, 1990 through
April 19, 2016. RESULTS: The review included 27 studies related to allergic
diseases and soft computing performances. We observed promising results with an
overall accuracy of 86.5%, mainly focused on asthmatic disease. The review
reveals that soft computing-based approaches are suitable for big data analysis
and can be very powerful, especially when dealing with uncertainty and poorly
characterized parameters. Furthermore, they can provide valuable support in case
of lack of data and entangled cause-effect relationships, which make it difficult
to assess the evolution of disease. CONCLUSIONS: Although most works deal with
asthma, we believe the soft computing approach could be a real breakthrough and
foster new insights into other allergic diseases as well.
PMID- 28413359
TI - Disulfide proteomics of rice cultured cells in response to OsRacl and probenazole
related immune signaling pathway in rice.
AB - BACKGROUND: Reactive oxygen species (ROS) production is an early event in the
immune response of plants. ROS production affects the redox-based modification of
cysteine residues in redox proteins, which contribute to protein functions such
as enzymatic activity, protein-protein interactions, oligomerization, and
intracellular localization. Thus, the sensitivity of cysteine residues to changes
in the cellular redox status is critical to the immune response of plants.
METHODS: We used disulfide proteomics to identify immune response-related redox
proteins. Total protein was extracted from rice cultured cells expressing
constitutively active or dominant-negative OsRacl, which is a key regulator of
the immune response in rice, and from rice cultured cells that were treated with
probenazole, which is an activator of the plant immune response, in the presence
of the thiol group-specific fluorescent probe monobromobimane (mBBr), which was a
tag for reduced proteins in a differential display two-dimensional gel
electrophoresis. The mBBr fluorescence was detected by using a charge-coupled
device system, and total protein spots were detected using Coomassie brilliant
blue staining. Both of the protein spots were analyzed by gel image software and
identified using MS spectrometry. The possible disulfide bonds were identified
using the disulfide bond prediction software. Subcellular localization and
bimolecular fluorescence complementation analysis were performed in one of the
identified proteins: Oryza sativa cold shock protein 2 (OsCSP2). RESULTS: We
identified seven proteins carrying potential redox-sensitive cysteine residues.
Two proteins of them were oxidized in cultured cells expressing DN-OsRac1, which
indicates that these two proteins would be inactivated through the inhibition of
OsRac1 signaling pathway. One of the two oxidized proteins, OsCSP2, contains 197
amino acid residues and six cysteine residues. Site-directed mutagenesis of these
cysteine residues revealed that a Cys140 mutation causes mislocalization of a
green fluorescent protein fusion protein in the root cells of rice. Bimolecular
fluorescence complementation analysis revealed that OsCSP2 is localized in the
nucleus as a homo dimer in rice root cells. CONCLUSIONS: The findings of the
study indicate that redox-sensitive cysteine modification would contribute to the
immune response in rice.
PMID- 28413360
TI - The CD31 molecule: a possible neuroprotective agent in acute ischemic stroke?
AB - BACKGROUND: The transmembrane receptor molecule CD31 is known to have
immunomodulatory functions, suggesting a possible neuroprotective effect in the
context of acute ischemic stroke by restricting an over-activation of secondary
immunological processes. This study examines the density of CD31+ cells in
mechanically extracted thrombi of stroke patients with the aim to test whether
the occurrence of CD31+ cells was associated with a beneficial clinical outcome
in those patients. METHODS: Thrombi of 122 consecutive patients with large
anterior circulation stroke were collected during intracranial mechanical
recanalization. Out of these, 86 immunostained specimens of adequate quality
could be analysed. The density of CD31+ cells was quantified and compared with
clinical outcome data of the affected patients. RESULTS: The density of CD31+
cells was positively related to early patient improvement (DeltaNIHSS, r = 0.283,
p = 0,012) with an even clearer relationship after exclusion of patients who died
in the early hospital phase (r = 0.371, p = 0.001). This finding stayed stable
also in the multivariate analysis after corrrection for other outcome-influencing
factors (p = 0.049). CONCLUSION: This study shows a stable relation between CD31+
cells and early clinical improvement of patients with acute ischemic stroke. This
finding is in line with recent reports showing immunomodulatory and potential
neuroprotective effects of CD31, suggesting that CD31 may be a promising
neuroprotective agent in stroke patients.
PMID- 28413361
TI - Cost-effectiveness analysis of the national decentralization policy of
antiretroviral treatment programme in Zambia.
AB - BACKGROUND: In resource-limited settings with a high prevalence of human
immunodeficiency virus (HIV) infection such as Zambia, decentralization of
HIV/acquired immunodeficiency syndrome (HIV/AIDS) treatment and care with
effective use of resources is a cornerstone of universal treatment and care.
OBJECTIVES: This research aims to analyse the cost effectiveness of the National
Mobile Antiretroviral Therapy (ART) Services Programme in Zambia as a means of
decentralizing ART services. METHODS: Cost-effectiveness analyses were performed
using a decision analytic model and Markov model to compare the original ART
programme, 'Hospital-based ART', with the intervention programme, Hospital-based
plus 'Mobile ART', from the perspective of the district government health office
in Zambia. The total cost of ART services, quality-adjusted life years (QALYs)
and incremental cost-effectiveness ratios (ICERs) were examined. RESULTS: The
mean annual per-patient costs were 1259.16 USD for the original programme and
2601.02 USD for the intervention programme, while the mean number of QALYs was
6.81 for the original and 7.27 for the intervention programme. The ICER of the
intervention programme relative to the original programme was 2965.17 USD/QALY,
which was much below the willingness-to-pay (WTP), or three times the GDP per
capita (4224 USD), but still over the GDP per capita (1408 USD). In the
sensitivity analysis, the ICER of the intervention programme did not
substantially change. CONCLUSION: The National Mobile ART Services Programme in
Zambia could be a cost-effective approach to decentralizing ART services into
rural areas in Zambia. This programme could be expanded to more districts where
it has not yet been introduced to improve access to ART services and the health
of people living with HIV (PLHIV) in rural areas.
PMID- 28413362
TI - Bone Loss in HIV Infection.
AB - Human immunodeficiency virus (HIV) infection is an established risk factor for
low bone mineral density (BMD) and subsequent fracture, and treatment with
combination antiretroviral therapy (cART) leads to additional BMD loss,
particularly in the first 1-2 years of therapy. The prevalence of low BMD and
fragility fracture is expected to increase as the HIV-infected population ages
with successful treatment with cART. Mechanisms of bone loss in the setting of
HIV infection are likely multifactorial, and include viral, host, and immune
effects, as well as direct and indirect effects of cART, particularly tenofovir
disoproxil fumarate (TDF) and the protease inhibitors (PIs). Emerging data
indicate that BMD loss following cART initiation can be mitigated by prophylaxis
with either long-acting bisphosphonates or vitamin D and calcium supplementation.
In addition, newer antiretrovirals, particularly the integrase strand transfer
inhibitors and tenofovir alafenamide (TAF), are associated with less intense bone
loss than PIs and TDF. However, further studies are needed to establish optimal
bone sparing cART regimens, appropriate screening intervals, and preventive
measures to address the rising prevalence of fragility bone disease in the HIV
population.
PMID- 28413363
TI - Wnt Signaling and Colorectal Cancer.
AB - The WNT signaling pathway is a critical mediator of tissue homeostasis and
repair, and frequently co-opted during tumor development. Almost all colorectal
cancers (CRC) demonstrate hyperactivation of the WNT pathway, which in many cases
is believed to be the initiating and driving event. In this short review, we
provide a focused overview of recent developments in our understanding of the WNT
pathway in CRC, describe new research tools that are enabling a deeper
understanding of WNT biology, and outline ongoing efforts to target this pathway
therapeutically.
PMID- 28413364
TI - Delivering Integrated Care to the Frail Elderly: The Impact on Professionals'
Objective Burden and Job Satisfaction.
AB - BACKGROUND: The impact of integrated working on professionals' objective burden
and job satisfaction was examined. An evidence-based intervention targeting frail
elderly patients was implemented in the Walcheren region of the Netherlands in
2010. The intervention involved the primary care practice as a single entry
point, and included proactive frailty screening, a comprehensive assessment of
patient needs, case management, multidisciplinary teams, care plans and
protocols, task delegation and task specialisation, a shared information system,
a geriatric care network and integrated funding. METHODS: A quasi-experimental
design with a control group was used. Data regarding objective burden involved
the professionals' time investments over a 12-month period that were collected
from patient medical records (n = 377) time registrations, transcripts of
meetings and patient questionnaires. Data regarding job satisfaction were
collected using questionnaires that were distributed to primary care and home
care professionals (n = 180) after the intervention's implementation. Within- and
between-groups comparisons and regression analyses were performed. RESULTS: Non
patient related time was significantly higher in the experimental group than in
the control group, whereas patient-related time did not differ. Job satisfaction
remained unaffected by the intervention. CONCLUSION AND DISCUSSION: Integrated
working is likely to increase objective burden as it requires professionals to
perform additional activities that are largely unrelated to actual patient care.
Implications for research and practice are discussed. [Current Controlled Trials
ISRCTN05748494].
PMID- 28413365
TI - Integrating the Principles of Evidence Based Medicine and Evidence Based Public
Health: Impact on the Quality of Patient Care and Hospital Readmission Rates in
Jordan.
AB - INTRODUCTION: Hospital readmissions impose not only an extra burden on health
care systems but impact patient health outcomes. Identifying modifiable
behavioural risk factors that are possible causes of potentially avoidable
readmissions can lower readmission rates and healthcare costs. METHODS: Using the
core principles of evidence based medicine and public health, the purpose of this
study was to develop a heuristic guide that could identify what behavioural risk
factors influence hospital readmissions through adopting various methods of
analysis including regression models, t-tests, data mining, and logistic
regression. This study was a retrospective cohort review of internal medicine
patients admitted between December 1, 2012 and December 31, 2013 at King Abdullah
University Hospital, in Jordan. RESULTS: 29% of all hospitalized patients were
readmitted during the study period. Among all readmissions, 44% were identified
as potentially avoidable. Behavioural factors including smoking, unclear follow
up and discharge planning, and being non-compliant with treatment regimen as well
as discharge against medical advice were all associated with increased risk of
avoidable readmissions. CONCLUSION: Implementing evidence based health programs
that focus on modifiable behavioural risk factors for both patients and
clinicians would yield a higher response in terms of reducing potentially
avoidable readmissions, and could reduce direct medical costs.
PMID- 28413367
TI - Discharge Planning: Screening Older Patients for Multidisciplinary Team Referral.
AB - The objective was to determine whether the Elders Risk Assessment Index can
predict multi-disciplinary team referral of older patients (>= 65 years) in
Emergency Department same-day discharges. The study identified 1,376 qualifying
individuals from a regional New Zealand hospital database. Of these, 12.7 % were
referred to the multi-disciplinary team. Univariate and multivariate analyses
were used to explore associations between the Index, its components, and other
demographic factors with referral. With every unit increase in the Index there
was a 9% increase in the odds of being referred. When the components of the Index
were analysed separately, an increased likelihood of being referred was
associated with not being married, having had a previous hospital admission of
more than five days, having chronic obstructive pulmonary disease, and being
older. Conversely, a decreased likelihood was associated with having diabetes.
When non-Index items were analysed it was found that females were more likely to
be referred than males and that Maori were less likely to be referred than New
Zealand Europeans. With adaptation, the Elders Risk Assessment Index may provide
a simple, cost-effective, and timely tool to assist in determining the need for
multi-disciplinary team referral for older people who present to the Emergency
Department.
PMID- 28413366
TI - Organizational Context and Capabilities for Integrating Care: A Framework for
Improvement.
AB - BACKGROUND: Interventions aimed at integrating care have become widespread in
healthcare; however, there is significant variability in their success.
Differences in organizational contexts and associated capabilities may be
responsible for some of this variability. PURPOSE: This study develops and
validates a conceptual framework of organizational capabilities for integrating
care, identifies which of these capabilities may be most important, and explores
the mechanisms by which they influence integrated care efforts. METHODS: The
Context and Capabilities for Integrating Care (CCIC) Framework was developed
through a literature review, and revised and validated through interviews with
leaders and care providers engaged in integrated care networks in Ontario,
Canada. Interviews involved open-ended questions and graphic elicitation.
Quantitative content analysis was used to summarize the data. RESULTS: The CCIC
Framework consists of eighteen organizational factors in three categories: Basic
Structures, People and Values, and Key Processes. The three most important
capabilities shaping the capacity of organizations to implement integrated care
interventions include Leadership Approach, Clinician Engagement and Leadership,
and Readiness for Change. The majority of hypothesized relationships among
organizational capabilities involved Readiness for Change and Partnering,
emphasizing the complexity, interrelatedness and importance of these two factors
to integrated care efforts. CONCLUSIONS: Organizational leaders can use the
framework to determine readiness to integrate care, develop targeted change
management strategies, and select appropriate partners with overlapping or
complementary profiles on key capabilities. Researchers may use the results to
test and refine the proposed framework, with a focus on the hypothesized
relationships among organizational capabilities and between organizational
capabilities and performance outcomes.
PMID- 28413368
TI - What Is Case Management? A Scoping and Mapping Review.
AB - The description of case management in research and clinical practice is highly
variable which impedes quality analysis, policy and planning. Case management
makes a unique contribution towards the integration of health care, social
services and other sector services and supports for people with complex health
conditions. There are multiple components and variations of case management
depending on the context and client population. This paper aims to scope and map
case management in the literature to identify how case management is described in
the literature for key complex health conditions (e.g., brain injury, diabetes,
mental health, spinal cord injury). Following literature searches in multiple
databases, grey literature and exclusion by health condition, community-based and
adequate description, there were 661 potential papers for data extraction. Data
from 79 papers (1988-2013) were analysed to the point of saturation (no new
information) and mapped to the model, components and activities. The results
included 22 definitions, five models, with 69 activities or tasks of case
managers mapped to 17 key components (interventions). The results confirm the
significant terminological variance in case management which produces role
confusion, ambiguity and hinders comparability across different health conditions
and contexts. There is an urgent need for an internationally agreed taxonomy for
the coordination, navigation and management of care.
PMID- 28413369
TI - Evaluation of Quality Indicators of Integrated Care in a Regional Psychiatry
Budget - A Pre-Post Comparison by Secondary Data Analysis.
AB - The Regional Psychiatry Budget (RPB), as a special arrangement within the German
Federal Hospital Refund Regulation, is based on the capitation principle. A lump
sum is allocated to a major inpatient care provider in a large region on a yearly
basis. Under this model, the provider is free to offer all forms of treatment and
to construct individual models of integrated care that specifically suit the
region and the needs of community members. The present study aimed to evaluate
selected aspects that represent a change in the psychiatric health status of
patients in the covered region under the conditions of the RPB. We performed a
secondary data analysis of administrative data of 19,913 cases generated by the
hospital in a pre-post comparison of the periods before and under RPB conditions.
The average length of an inpatient stay was reduced by approximately 22 % and
could be partially replaced by day care. Selected indicators suggest equal or
higher quality of care with stable cost in the population in need of psychiatric
care in the district.
PMID- 28413370
TI - Analysis of building deformation in landslide area using multisensor PSInSARTM
technique.
AB - Buildings are sensitive to movements caused by ground deformation. The mapping
both of spatial and temporal distribution, and of the degree of building damages
represents a useful tool in order to understand the landslide evolution,
magnitude and stress distribution. The high spatial resolution of space-borne SAR
interferometry can be used to monitor displacements related to building
deformations. In particular, PSInSAR technique is used to map and monitor ground
deformation with millimeter accuracy. The usefulness of the above mentioned
methods was evaluated in San Fratello municipality (Sicily, Italy), which was
historically affected by landslides: the most recent one occurred on 14th
February 2010. PSInSAR data collected by ERS 1/2, ENVISAT, RADARSAT-1 were used
to study the building deformation velocities before the 2010 landslide. The X
band sensors COSMO-SkyMed and TerraSAR-X were used in order to monitor the
building deformation after this event. During 2013, after accurate field
inspection on buildings and structures, damage assessment map of San Fratello
were created and then compared to the building deformation velocity maps. The
most interesting results were obtained by the comparison between the building
deformation velocity map obtained through COSMO-SkyMed and the damage assessment
map. This approach can be profitably used by local and Civil Protection
Authorities to manage the post-event phase and evaluate the residual risks.
PMID- 28413371
TI - The Synthesis of Novel Oxazolinylphosphinic Esters and Amides and Application to
the Cyanosilylation of Aldehydes.
AB - A new class of modular functionalized oxazolines are synthesized using a simple,
novel one-pot method under inert moisture-free conditions. Then the oxazolines
can be further elaborated to phosphine-containing oxazolines. The first step is
to synthesize intermediates via the reaction of 2 - hydroxybenzonitrile or 2
aminobenzonitrile with chiral amino alcohols, subsequent reactions with phosphine
chlorides, providing products in moderate yields. Product structures are fully
characterized by NMR, IR, MS and X-Ray analyses. These compounds are found to be
highly active catalysts for the cyanosilylation of prochiral benzaldehyde (20-96%
yield).
PMID- 28413372
TI - Electrochemical Impedance Spectroscopy Study of Concanavalin A Binding to Self
Assembled Monolayers of Mannosides on Gold Wire Electrodes.
AB - The interactions of the lectin Concanavalin A (Con A) with self-assembled
monolayers (SAMs) of thiolated mono-, di-, and tri-mannosides were studied on the
surface of gold wires using electrochemical impedance spectroscopy (EIS). The
SAMs of mannosides were prepared either pure or along with thiolated triethylene
glycol (TEG) at different molar ratios (1:1, 1:2, 1:4, 1:9, and 1:19) to better
understand and optimize the interaction conditions. The charge-transfer
resistance of the [Fe(CN)6]3-/4- redox probe was compared before and after the
interaction at different concentrations of Con A to determine the equilibrium
dissociation constant (Kd) and limit of detection (LOD). Values of Kd were found
in the nanomolar range showing multivalent interactions between mannosides and
Con A, and LOD was found ranging from 4-13 nM depending on the type of mannoside
SAM used. Analysis using the Hill equation suggests negative cooperativity in the
binding behavior. Peanut agglutinin was used as a negative control, and cyclic
voltammetry was used to further support the experiments. We have found that
neither the pure nor the widely dispersed monolayers of mannosides provide the
conditions for optimal binding of Con A. The binding of Con A to these SAMs is
sensitive to the molar ratio of the mannoside used to prepare the SAM and to the
structure of the mannoside. A simple cleaning method has also been shown to
regenerate the used gold wire electrodes. The results from these experiments
contribute to the development of simple, cheap, selective, and sensitive EIS
based bioassays, especially for lectin-carbohydrate interactions.
PMID- 28413373
TI - Electrochemical impedance spectroscopy study of carbohydrate-terminated
alkanethiol monolayers on nanoporous gold: Implications for pore wetting.
AB - Electrochemical impedance spectroscopy (EIS) is used to compare the apparent
electron transfer rate constant (kapp) for a series of alkanethiol and of
carbohydrate-terminated alkanethiol self-assembled monolayers (SAMs) on both flat
gold and on nanoporous gold (np-Au). Using the surface area for np-Au determined
by oxide stripping, the values of kapp for the alkanethiol modified np-Au are
initially over two orders of magnitude smaller than the values found on flat Au.
This result provides evidence that the diffusing redox probe Fe(CN)63-/4- only
accesses a fraction of the np-Au surface after alkanethiol modification
suggesting very limited wetting of the internal pores due to the hydrophobic
nature of these surfaces. In contrast, for np-Au modified by carbohydrate
terminated (mannose or galactose) alkanethiols the values of kapp are about 10-40
fold smaller than on flat gold, suggesting more extensive access of the diffusing
redox probe within the pores and better but still incomplete wetting, a result
also found for modification of np-Au with mercaptododecanoic acid. A short chain
PEG thiol derivative is found to result in a comparison of kapp values that
suggests nearly complete wetting of the internal pores for this highly
hydrophilic derivative. These results are of significance for the potential
applications of SAM modified np-Au in electrochemical sensors, especially for
those based on carbohydrate-protein recognition, or those of np-Au modified by
SAMs with polar terminal groups.
PMID- 28413374
TI - Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics.
AB - INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common
cause of cancer-related death in Europe with a 5-year survival rate of <5%.
Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the
majority of cases malignancy is discovered too late for curative treatment. There
is at present no reliable diagnostic marker for PDAC available. OBJECTIVES: The
aim of the study was to identify single blood-based metabolites or a panel of
metabolites discriminating PDAC and CP using liquid chromatography-mass
spectrometry (LC-MS). METHODS: A discovery cohort comprising PDAC (n = 44) and CP
(n = 23) samples was analyzed by LC-MS followed by univariate (Student's t test)
and multivariate (orthogonal partial least squares-discriminant analysis (OPLS
DA)) statistics. Discriminative metabolite features were subject to raw data
examination and identification to ensure high feature quality. Their
discriminatory power was then confirmed in an independent validation cohort
including PDAC (n = 20) and CP (n = 31) samples. RESULTS: Glycocholic acid, N
palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers
discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of
five metabolites including the aforementioned three metabolites as well as
phenylacetylglutamine (PAGN) and chenodeoxyglycocholate. CONCLUSION: Using LC-MS
based metabolomics we identified three single metabolites and a five-metabolite
panel discriminating PDAC and CP in two independent cohorts. Although further
study is needed in larger cohorts, the metabolites identified are potentially of
use in PDAC diagnostics.
PMID- 28413376
TI - Ferromagnetic, folded electrode composite as a soft interface to the skin for
long-term electrophysiological recording.
AB - This paper introduces a class of ferromagnetic, folded, soft composite material
for skin-interfaced electrodes with releasable interfaces to stretchable,
wireless electronic measurement systems. These electrodes establish intimate,
adhesive contacts to the skin, in dimensionally stable formats compatible with
multiple days of continuous operation, with several key advantages over
conventional hydrogel based alternatives. The reported studies focus on aspects
ranging from ferromagnetic and mechanical behavior of the materials systems, to
electrical properties associated with their skin interface, to system-level
integration for advanced electrophysiological monitoring applications. The work
combines experimental measurement and theoretical modeling to establish the key
design considerations. These concepts have potential uses across a diverse set of
skin-integrated electronic technologies.
PMID- 28413375
TI - Inflammatory Cyclooxygenase Activity and PGE2 Signaling in Models of Alzheimer's
Disease.
AB - The inflammatory response is a fundamental driving force in the pathogenesis of
Alzheimer's disease (AD). In the setting of accumulating immunogenic Abeta
peptide assemblies, microglia, the innate immune cells of the brain, generate a
non-resolving immune response and fail to adequately clear accumulating Abeta
peptides, accelerating neuronal and synaptic injury. Pathological, biomarker, and
imaging studies point to a prominent role of the innate immune response in AD
development, and the molecular components of this response are beginning to be
unraveled. The inflammatory cyclooxygenase-PGE2 pathway is implicated in pre
clinical development of AD, both in epidemiology of normal aging populations and
in transgenic mouse models of Familial AD. The cyclooxygenase-PGE2 pathway
modulates the inflammatory response to accumulating Abeta peptides through
actions of specific E-prostanoid G-protein coupled receptors.
PMID- 28413378
TI - Is Age an Independent Factor for Prostate Cancer? A Paired Analysis.
AB - INTRODUCTION: Prostate cancer is the most prevalent malignant neoplasia among men
worldwide. Several prognostic factors, including Gleason's score, the measurement
of serum prostate-specific antigen (PSA) and the evaluation of the percentage of
fragments affected by cancer on prostate biopsy, have already been established.
Age alone, however, has yet to be studied as a prognostic factor independently
from other known factors. The aim of the present study was to compare the
characteristics and the evolution of prostate cancer in different age groups
using a paired analysis for patients with equivalent known prognostic factors. In
addition, we aimed to determine the true impact of age on the prognosis of
prostate cancer. MATERIAL AND METHODS: The data from 2,283 patients subjected to
radical retropubic prostatectomy between 1998 and 2009 were reviewed. The
patients were divided into three age groups: < 55 years old, between 56 and 65
and > 65 years old. Each patient was matched to another patient in the other
groups who had the same PSA range (< 4.0, between 4.0 and 10.0 and > 10), Gleason
score on the surgical specimen and prognostic range of positive fragments in the
prostate biopsy (< 33%, between 34 and 50% and > 50%). After pairing, each group
consisted of 215 patients, who were compared using the biochemical recurrence of
the disease (PSA > 0.2), the interval for biochemical relapse, extra-capsular
invasion and invasion of the seminal vesicles or the lymph nodes. RESULTS. No
significant difference was observed between the groups regarding the frequency of
relapses, interval of relapse, extra-capsular invasion and invasion of the
seminal vesicles or lymph nodes. DISCUSSION: None of the studied factors were
affected by the age of the patients. Therefore, patients of different ages had
tumors with similar characteristics and behaviors. CONCLUSION: When assessed
separately, without the effects of the main prognostic factors, age does not
appear to be an independent prognostic factor for prostate cancer.
PMID- 28413379
TI - Effect of Microsurgical Subinguinal Varicocele Repair on Chronic Dull Scrotal
Pain in Men with Grade II-III Lesions.
AB - INTRODUCTION: We aimed to evaluate the effectiveness of microsurgical subinguinal
varicocele repair in patients with grade II-III lesions and chronic dull scrotal
pain. MATERIALS AND METHODS: A total of 29 patients with grade II-III varicocele
and chronic dull scrotal pain that had a microsurgical subinguinal varicocele
repair were included in the study. They were followed-up for 6-12 months
including pain assessment and scrotal examination. RESULTS: Of the 29 patients,
28 (97%) reported complete resolution of pain with no palpable varicocele on
scrotal examination. No cases of testicular atrophy or hydrocele formation were
reported. CONCLUSION: These results indicated that microsurgical varicocele
repair should be considered in patients with grade II-III lesions and chronic
dull scrotal pain.
PMID- 28413377
TI - Mimicry of Appendicitis Symptomatology in Congenital Anomalies and Diseases of
the Genitourinary System and Pregnancy.
AB - INTRODUCTION: Appendicitis is a prevailing cause of acute abdomen, but is often
difficult to diagnose due to its wide range of symptoms, anatomical variations,
and developmental abnormalities. Urological disorders of the genitourinary tract
may be closely related to appendicitis due to the close proximity of the appendix
to the genitourinary tract. This review provides a summary of the urological
complications and simulations of appendicitis. Both typical and urological
symptoms of appendicitis are discussed, as well as recommended diagnostic and
treatment methods. METHODS: Medline searches were conducted via PubMed in order
to incorporate data from the recent and early literature. RESULTS: Urological
manifestations of appendicitis affect the adrenal glands, kidney,
retroperitoneum, ureter, bladder, prostate, scrotum, and penis. Appendicitis in
pregnancy is difficult to diagnose due to variations in appendiceal position and
trimester-specific symptoms. Ultrasound, CT, and MRI are used in diagnosis of
appendicitis and its complications. Treatment of appendicitis may be done via
open appendectomy or laparoscopic appendectomy. In some cases, other surgeries
are required to treat urological complications, though surgery may be avoided
completely in other cases. CONCLUSION: Clinical presentation and complications of
appendicitis vary among patients, especially when the genitourinary tract is
involved. Appendicitis may mimic urological disorders and vice versa. Awareness
of differential diagnosis and proper diagnostic techniques is important in
preventing delayed diagnosis and possible complications. MRI is recommended for
diagnosis of pregnant patients. Ultrasound is preferred in patients exhibiting
typical symptoms.
PMID- 28413380
TI - Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor
Alpha in Cancer Bladder: Schistosomal and Non-Schistosomal.
AB - INTRODUCTION: Overexpression of epidermal growth factor receptor (EGFR) has been
described in several solid tumors including bladder cancer. Transforming growth
factor alpha (TGFalpha) is frequently deregulated in neoplastic cells and plays a
role in the development of bladder cancer. TGFalpha-EGFR ligand-receptor
combination constitutes an important event in multistep tumorigenesis. METHODS:
This study was done on 30 bladder biopsies from patients with urothelial
carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control
bladder specimens. All were immuohistochemically stained with EGFR and TGFalpha
antibodies. RESULTS: EGFR and TGFalpha were over-expressed in higher grades and
late stages of bladder cancer. Moreover, they show higher expression in squamous
cell carcinoma compared to urothelial carcinoma and in schistosomal associated
lesions than in non-schistosomal associated lesions. CONCLUSION: EGFR and
TGFalpha could be used as prognostic predictors in early stage and grade of
bladder cancer cases, especially those with schistosomal association. In addition
they can help in selecting patients who can get benefit from anti-EGFR molecular
targeted therapy.
PMID- 28413381
TI - Delayed Cytoreductive Nephrectomy Following Three Years of Targeted Therapy for
Metastatic Renal Cell Carcinoma.
AB - We present a 55-year-old male, with good performance status who was diagnosed
with a case of metastatic renal cell carcinoma following a pathologic femur
fracture. Despite good performance status, multifocal metastases and poor
prognostic features portended a grim prognosis with predicted overall survival of
less than nine months. On initial presentation, he was excluded from
cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not
pursued as the primary tumor was to be left in situ. The patient was reconsidered
for cytoreductive nephrectomy after sustained response to fifth line targeted
therapies with shrinkage of tumor burden. The post-operative course was
uneventful and the patient was discharged home on postoperative day one.
Temsirolimus was resumed one week after surgery and the patient reported
returning to his normal activities at the two week follow-up visit. We highlight
important clinical features of metastatic renal cell carcinoma, the surgical
considerations for cytoreductive nephrectomy and the detailed multidisciplinary
care the patient received throughout this case report.
PMID- 28413382
TI - Angiomyolipoma with Epithelial Cysts Masquerading as a Cystic Renal Cell
Carcinoma.
AB - Angiomyolipoma with epithelial cysts (AMLEC) is a very uncommon renal tumor.
AMLEC has a characteristic histological appearance and immunohistochemical
staining pattern, knowledge of which should preclude misdiagnosis by
pathologists. We present a rare case of an AMLEC which was suspected to be a
cystic renal cell carcinoma radiologically. We describe the characteristic
immunological staining pattern and ultrastructural features of this lesion and
discuss the potential differential diagnoses.
PMID- 28413384
TI - Pyogenic Granuloma of the Penis: An Uncommon Lesion with Unusual Presentation.
AB - We present the case of a 37-year-old man who presented with a penile lesion that
engorged on erection. Ultrasound examination demonstrated vascularity of the
lesion and the decision was made to perform a complete excision. Histological
analysis confirmed the diagnosis of a pyogenic granuloma of the penis. Follow-up
demonstrated no recurrence at 3 months.
PMID- 28413383
TI - Prostate Cancer: How Young is too Young?
AB - Prostate cancer is the most common non-cutaneous malignancy in men. It is
generally considered a cancer of the elderly, and the median age of presentation
is 68 years. However 10% of new diagnoses in the USA occur in men aged <= 55
years. This may be due to more prevalent screening nowadays, and may also reflect
the diagnosis of an increasingly recognized but underappreciated entity, i.e.
early-onset prostate cancer. Patients with early onset prostate cancer pose
unique challenges. Current data suggest that early-onset prostate cancer is a
distinct phenotype-from both an etiological and clinical perspective- that
deserves further attention. We present a case of a 28-year-old man who presented
with lower urinary tract symptoms and was diagnosed with advanced stage prostate
cancer.
PMID- 28413385
TI - Calciphylaxis Presenting with Various Symptoms: A Case Report.
AB - Calciphylaxis causes ischemia in multiple organs and skin ulcers owing to
progressive calcification in small and medial arteries. It has a poor prognosis
and often occurs in patients with hyperparathyroidism associated with end-stage
renal failure and those undergoing hemodialysis. Here, we present a case of
calciphylaxis associated with a wide range of symptoms, including lower thigh
skin ulcers, a rectovaginal fistula, and femoral neck fracture. The patient
underwent multiple treatments. However, she eventually died of cardiac failure.
PMID- 28413386
TI - Severe, Malignant Acanthosis Nigricans Associated with Adenocarcinoma of the
Endometrium in a Young Obese Female.
AB - Acanthosis nigricans (AN) is a dermatopathy associated with insulin-resistance,
drugs, endocrine disorders, chromosomal abnormalities (benign AN), and neoplasia
(malignant AN). Malignant AN (MAN) is a rare paraneoplastic skin syndrome most
commonly associated with gastric adenocarcinoma and other intra-abdominal
malignancies. We report the case of a 28-year-old female with AN associated with
obesity, insulin resistance, and endometrial adenocarcinoma. Although rare, MAN
is often an initial sign of malignancy and must trigger extensive investigation,
particularly in patients with sudden development of possibly paraneoplastic
dermatoses or in patients diagnosed with benign AN with any atypical features.
PMID- 28413387
TI - Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was
Refractory to Corticosteroid and Omalizumab Treatments.
AB - Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment
of severe allergic asthma and inhibits IgE binding to FcepsilonRI. According to
increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic
approach for bullous pemphigoid (BP). Rituximab has been reported to be effective
in various autoimmune diseases, including autoimmune bullous dermatoses. A
specific protocol for the use of rituximab to treat BP patients is not yet
available. There are only small case series and case reports about the efficacy
and safety of rituximab in BP. Here we present a young BP patient who responded
well to rituximab therapy and was refractory to conventional and omalizumab
therapies although he had elevated IgE levels and eosinophilia. Our case supports
the knowledge about the effectiveness and safety of rituximab not only in
pemphigus but also in BP. On the other hand, although it did not work in our
case, omalizumab may be a potentially effective agent in some carefully selected
patients with certain subtypes of BP.
PMID- 28413388
TI - A Case Report of Cushing's Disease Presenting as Hair Loss.
AB - Cushing's syndrome is a rare endocrine disorder that comprises a large group of
signs and symptoms resulting from chronic exposure to excess corticosteroids.
Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone
production from a pituitary adenoma, which is referred to as Cushing's disease.
Most of the signs and symptoms are nonspecific and common in the general
population, making a diagnosis often challenging. However, several dermatological
manifestations, such as fragile skin, easy bruising, and reddish purple striae,
are more discriminatory. Because uncontrolled Cushing's syndrome of any etiology
is associated with substantial morbidity, including increased cardiovascular
disease and mortality, it is important to make an early diagnosis. Unfortunately,
median delays of 2 years to diagnosis have been reported. We report a case of a
woman who had multiple dermatological findings, including facial plethora, easy
bruising, violaceous striae, hirsutism, and acne, the latter 2 signs reflecting
androgen excess. Of interest, our patient presented with a chief complaint of
hair loss, a common complaint in the general population that occurs with a
greater frequency in patients with Cushing's disease and is attributed to
androgenetic alopecia, but it is rarely the presenting symptom.
PMID- 28413389
TI - A Case of Right Atrial Obliteration Caused by Intracardiac Extension of
Hepatocellular Carcinoma.
AB - As the fifth most common malignancy worldwide, hepatocellular carcinoma (HCC) is
a frequently encountered clinical entity. Symptomatology associated with the
diagnosis includes hepatic dysfunction and pain from capsular spread.
Additionally, due to its propensity for vascular spread, extrahepatic
intravascular involvement can also be seen. We present a unique case of
intracardiac involvement of HCC. Originally diagnosed as acute on chronic heart
failure, echocardiography revealed the symptom source - tumor obliteration of the
right atrium. Clinical case presentation and management, along with radiographic
images are presented. A review of the current literature highlights this uncommon
presentation and the need for clinical suspicion of cardiac involvement in
patients with a history of HCC presenting with heart failure.
PMID- 28413390
TI - A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic
Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous
Neoplasm: A Case Report.
AB - Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms,
most of which are benign and do not communicate with the pancreatic duct.
Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal
adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year
old Japanese woman presented with a 10-mm multilocular cystic lesion at the
pancreatic body. Magnetic resonance pancreatography showed stenosis of the main
pancreatic duct at the pancreatic body and dilatation of the distal side of the
main pancreatic duct. Furthermore, communication between the cystic lesion and
the main pancreatic duct was suspected based on magnetic resonance
pancreatography findings. Distal pancreatectomy was performed under the
preoperative diagnosis of intraductal papillary mucinous neoplasm.
Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat
epithelium with clear cytoplasm and was thus diagnosed as a serous cystic
neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the
main and branch pancreatic ducts. Histological examination revealed no
communication between the serous cystic neoplasm and the pancreatic ducts.
Immunohistochemically, the epithelium of the serous cystic neoplasm showed
positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the
PanIN showed negative staining. A serous cystic neoplasm coexisting with another
pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic
ducts coexists with a serous cystic neoplasm, as in this case, the lesion
clinically mimics an intraductal papillary mucinous neoplasm.
PMID- 28413391
TI - Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non
Small Cell Lung Adenocarcinoma.
AB - INTRODUCTION: While epidermal growth factor receptor (EGFR) inhibitors have
improved progression-free survival in patients with non-small cell lung cancer
(NSCLC), one of the most common adverse effects is papulopustular skin eruption,
which is frequently severe enough to be treated with oral minocycline or
doxycycline. CASE: We present a case of an 87-year-old man who developed a severe
papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of
the eruption with 100 mg of minocycline twice daily for 8 months eventually led
to blue-gray skin hyperpigmentation. After 30 months, this side effect was
recognized as minocycline drug deposition, which was confirmed with skin biopsy.
DISCUSSION: Compliance with EGFR inhibitor therapy in NSCLC is often challenging
due to common side effects, most notably cutaneous skin eruptions. Treatment of
cutaneous toxicities is important to preserve patient compliance with targeted
cancer therapy. Use of minocycline to treat the most common cutaneous side effect
(papulopustular eruption) can in turn cause blue-black skin, eye, or tooth
discoloration that can nullify its benefits, resulting in suboptimal patient
adherence to cancer therapy. Although this adverse effect is well known in
dermatology literature as a risk when using minocycline to treat acne, rosacea,
or blistering disorders, it is less well documented in oncology literature. We
present this case to highlight the need for greater consideration of unique
patient characteristics in selecting an oral antibiotic as a treatment modality
for EGFR inhibitor skin toxicities.
PMID- 28413392
TI - T-Cell Lymphoma in a Patient with Neurofibromatosis Type 1 and AIDS.
AB - Neurofibromatosis type 1 (NF1) and AIDS are risk factors for the development of
malignant neoplasms, including hematological malignancies, such as non-Hodgkin
lymphoma. NF1 is an autosomal dominant disease that primarily manifests as cafe
au-lait spots, dermal neurofibromas, axillary and/or inguinal ephelides or
freckles, plexiform neurofibromas, Lisch nodules, and bone deformities. In this
report, we present a 38-year-old female patient with NF1 from childhood and AIDS
who developed peripheral T-cell lymphoma with good response to chemotherapeutic
treatment.
PMID- 28413393
TI - Circulating Tumor Cell Count Can Be a Useful Prognostic Factor in Lung Resection
via Cardiopulmonary Bypass.
AB - Tumor resection with cardiopulmonary bypass (CPB) remains controversial in the
field of oncology. Here, we present a 57-year-old male patient with locally
advanced squamous cell carcinoma. The tumor was located in the left hilum and
invaded the left atrium. Complete resection, left pneumonectomy combined with
partial left atrium resection, was achieved using CPB. We evaluated the
circulating tumor cell (CTC) counts, as a surrogate for micrometastasis, in
peripheral blood and the CPB circuit. Both CTC counts were 0, which could
indicate local disease without micrometastasis. CTC count may be a useful
indicator for tumor resection with CPB in lung cancer.
PMID- 28413394
TI - Significant Amelioration of Tracheal Stenosis following Lenvatinib in a Patient
Who Has Anaplastic Thyroid Carcinoma with Bronchomediastinal Infiltration: A Case
Report.
AB - BACKGROUND: Anaplastic thyroid carcinoma has an extremely poor prognosis, and no
known drugs have exhibited acceptable efficacy. In recent years, novel anticancer
tyrosine kinase inhibitors have been developed. We encountered a case of tracheal
stenosis due to mediastinal and tracheal infiltration of anaplastic carcinoma for
which lenvatinib exhibited remarkable effects; owing to this, airway management
could be performed, even though the patient's condition was considered critical.
CASE REPORT: A 55-year-old man presented with locally advanced anaplastic thyroid
carcinoma that was observed to have mediastinal infiltration. Tracheal stenosis
due to infiltration of the trachea occurred, and the condition of the patient
rapidly deteriorated. Radiation and chemotherapy consisting of cetuximab,
cisplatin, and fluorouracil were ineffective, but his tracheal stenosis was
relieved 2 weeks after initiation of lenvatinib, after which the patient could be
discharged. However, the lenvatinib was ineffective for his liver, bone, and
brain metastatic lesions, and the patient remained in a critical condition.
CONCLUSION: We encountered a case in which lenvatinib was effective for locally
advanced anaplastic thyroid carcinoma, leading to an improvement in quality of
life and a prolonged life. The drug was effective for the primary lesion, but
mixed efficacy was noted for distant metastatic lesions.
PMID- 28413395
TI - A Case of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis Treated
with Preoperative FOLFOX Chemotherapy Followed by Radical Subtotal Gastrectomy
and D2 Lymph Node Dissection.
AB - We report the case of a 73-year-old female who was diagnosed with advanced
gastric cancer. Esophagogastroduodenoscopy was used to diagnose Borrmann type 3
advanced gastric cancer located at the gastric antrum. A biopsy revealed poorly
differentiated adenocarcinoma. Abdominopelvic computed tomography (CT) and 18F
fluorodeoxyglucose positron emission tomography-CT (FDG-PET-CT) scans
demonstrated multiple lymph node metastases, including the para-aortic lymph
nodes. Systemic chemotherapy with 5-fluoruracil (5-FU), oxaliplatin, and
leucovorin (FOLFOX) was initiated. An abdominopelvic CT scan taken after 4 cycles
of chemotherapy showed improvement in the ulceroinfiltrative gastric lesion and
marked regression of several enlarged lymph nodes. Consequently, we performed a
subtotal gastrectomy with D2 lymphadenectomy. The postoperative histopathological
report was early gastric carcinoma with no lymph node metastasis in the 48
resected lymph nodes. Another 4 cycles of FOLFOX chemotherapy were performed
after surgery. A FDG-PET-CT scan taken 12 months postoperatively showed no
definite evidence of local recurrence or distant metastasis, and the previously
noted retroperitoneal lymph nodes had disappeared. A FDG-PET-CT taken 16 months
postoperatively showed multiple lymph node metastases, including the left
supraclavicular lymph node. Despite 8 cycles of secondary chemotherapy with 5-FU,
irinotecan, and leucovorin (FOLFIRI) and radiotherapy, the patient died 38 months
after the operation.
PMID- 28413396
TI - Mammary Analogue Secretory Carcinoma Presenting as a Cervical Lymph Node
Metastasis of Unknown Primary Site: A Case Report.
AB - BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a pathological entity
arising in the salivary glands first described by Skalova et al. [Am J Surg
Pathol 2010;34: 599-608]. Here, we report the first case of MASC presenting as a
cervical lymph node metastasis of unknown primary site together with a brief
review of the literature. CASE REPORT: We present a 74-year-old male with a
painless lump in his left neck. Based on the fine-needle aspiration cytological
findings, a possible malignant tumor was suspected. No evidence of a primary
lesion was observed using imaging modalities including positron emission
tomography/computed tomography. The patient underwent an ipsilateral modified
radical neck dissection. Immunohistochemical staining showed that the neoplastic
cells were positive for S100 protein and GATA3. A rearrangement of the ETV6 gene
was noted during fluorescence in situ hybridization, and the final
histopathological diagnosis was MASC. CONCLUSION: We encountered a MASC
presenting as a cervical lymph node metastasis of unknown primary site. No
adjuvant therapy was administered, and no local recurrence or metastatic disease
has been detected during a follow-up period of 9 months. This is the first case
report of MASC presenting as a cervical lymph node metastasis of unknown primary
site and suggests the new properties of MASC.
PMID- 28413397
TI - Primary Extranodal Diffuse Large B-Cell Lymphoma of the Prostate: A Case Report.
AB - We report a case of primary diffuse large B-cell lymphoma of the prostate in a 54
year-old Caucasian male who presented with urinary retention and benign prostatic
hyperplasia. We discuss the rare presentation of this disease and its
clinicopathologic features and review the literature for up-to-date information
on the diagnosis and clinical management. Despite the low incidence of lymphoma
involving the prostate gland, it should always be considered as part of the
differential diagnosis in cases of prostate gland enlargement with urinary tract
obstructive symptoms resistant to medical therapy. Treatment modalities for this
rare disease are also discussed.
PMID- 28413398
TI - Desmoid Fibromatosis of the Abdominal Wall: Surgical Resection and Reconstruction
with Biological Matrix Egis(r).
AB - Desmoid tumor is a rare monoclonal fibroblast proliferation that is regarded as
benign. The clinical management of desmoid tumors is very complex and requires a
multidisciplinary approach because of the unpredictable disease course. For those
cases localized in the anterior abdominal wall, symptomatic and unresponsive to
medical treatment, radical resection and reconstruction with a prosthetic device
are indicated. We present here a case of desmoid fibromatosis of the left
anterolateral abdominal wall with a marked increase of the mass that required a
large excision followed by reconstruction with biological matrix. The fact that
it can be incorporated in patient tissue without a fibrotic response and that it
can resist future infections, together with a very competetive price, made the
new collagen matrix Egis(r) our first choice.
PMID- 28413399
TI - HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1
Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th
Century.
AB - INTRODUCTION: At the onset of the 20th century, ancient clinical observations of
cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They
were reported from 1914 to 1960, but remained unexplained. In 1983, in San
Francisco, Calif., USA, cancer epidemics were related to infections by the human
immunodeficiency virus type 1 (HIV-1) known as AIDS disease. Yet since 1996, it
is known that HIV-1 strains are not the only ones involved. In Sub-Saharan
Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1) and genital
recurrent herpes simplex virus type 2 (HSV-2) appeared many times prior to
infection by HIV-1. CASE REPORTS: Data on these ancient medical observations
regarding African cancer epidemics can today be referred to as the relationship
between the unfortunate immune deficiency of herpes in Bantu populations and HIV
1 viral strains. For centuries, the Bantu populations dispersed in forests were
living in close proximity to chimpanzees infected by simian immunodeficiency
virus (SIV) and were exposed to SIV contamination which became HIV-1 in human
beings. Presently, these unexplained Bantu cancer epidemics can be linked to the
viral partnership of HSV-1/HSV-2 to HIV-1 strains. CONCLUSION: The key issue is
now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment
administered early during childhood to Bantu populations will offer a mean of
preventing herpes diseases related to HIV-1 infection and hence avoid cancer
epidemics.
PMID- 28413400
TI - Autonomic Dysregulation, Cognitive Impairment, and Symptoms of Psychosis as an
Unusual Presentation in an Anti-Aquaporin 4-Positive Patient.
AB - We present the unusual case of a patient with an aquaporin 4 antibody
seropositive neuromyelitis optica spectrum disorder who presented with autonomic
dysregulation, cognitive impairment, and symptoms of psychosis. Only a few
previous cases have been described with similar psychiatric symptoms. Brain MRI
showed an abnormal hyperintense T2 signal of the hypothalamus and, to a lesser
extent, a minor hyperintense signal of the right optic nerve. Her symptoms and MR
abnormalities improved after high-dose methylprednisolone.
PMID- 28413401
TI - Parkinsonism in Association with Dihydropteridine Reductase Deficiency.
AB - We report a 16-year-old man with disorders of tetrahydrobiopterin metabolism due
to dihydropteridine reductase (DHPR) deficiency. He revealed moderate mental
retardation, parkinsonism, and spastic paralysis with levodopa and 5
hydroxytryptophan (5-HTP) supplementation from the age of 2 months. Brain MRI
showed high intensity areas in bilateral frontal and posterior deep white matter
on fluid-attenuated inversion recovery (FLAIR). Coronal FLAIR image showed a high
signal in bilateral pyramidal tracts. Single photon computed tomography (SPECT)
imaging of the dopamine transporter was normal. This imaging indicates no
dopaminergic cell loss. Our patient had no motor fluctuations or dyskinesias.
Early diagnosis and replacement treatment might lead to a favorable outcome.
PMID- 28413402
TI - Paraneoplastic Peripheral Nervous System Manifestations of Renal Cell Carcinoma:
A Case Report and Review of the Literature.
AB - Neurologic symptoms secondary to a paraneoplastic syndrome may be the presenting
manifestation of a previously undiagnosed cancer, and alertness to these
syndromes may provide an opportunity for early detection and treatment of a
cancer. Paraneoplastic weakness is a rare manifestation of renal cell carcinoma
and may present with variable electrophysiological features. We present a case of
a patient with progressive weakness, sensory changes, and urinary retention, with
electrophysiological features suggestive of a complex peripheral nervous system
syndrome. Ultimately, a renal cell mass was detected and resected, resulting in
significant clinical improvement. We review the literature, cataloging the known
neurologic syndromes and antibodies associated with renal cell carcinoma. This
case highlights that paraneoplastic neurological disorders associated with RCC
can take on many features and provides a resource to practitioners for early
detection of a neurologic paraneoplastic syndrome arising from renal cell
carcinoma.
PMID- 28413404
TI - Yellow Pattern 577-nm Micropulse Laser: Treatment of Macular Edema from Radiation
Retinopathy - A Case Report.
AB - We report a case of a 60-year-old Asian male who developed radiation retinopathy
23 years after initial radiotherapy for nasopharyngeal carcinoma and was
successfully treated with yellow pattern 577-nm micropulse laser. Secondary
macular edema and visual acuity improved following a single treatment session
with minimal scarring. Yellow pattern micropulse laser is a safe and effective
treatment for macular edema secondary to radiation retinopathy.
PMID- 28413405
TI - Intravitreal Aflibercept in Recalcitrant Radiation Maculopathy due to External
Beam Radiotherapy for Nasopharyngeal Cancer: A First Case Report.
AB - PURPOSE: To present the safety and efficacy of intravitreal aflibercept (Eylea)
in a patient with radiation maculopathy secondary to external beam radiotherapy
for nasopharyngeal cancer unresponsive to other therapeutic options. METHODS: A
73-year-old female presented with decreased visual acuity in both eyes 18 months
after completing 47 external beam cycles of radiation for nasopharyngeal cancer.
On presentation, her best corrected visual acuity was 6/60 in the right eye and
counting fingers from 1 meter in the left eye. She received 5 bevacizumab
injections in the right eye and 7 bevacizumab injections in the left eye over the
last year without any improvement. A treatment with intravitreal injections of
aflibercept was recommended in both eyes. RESULTS: The patient received 3
intravitreal aflibercept injections (2 mg/0.05 mL) in each eye every 4 weeks. The
visual acuity improved from 6/60 to 6/12 in the right eye and from counting
fingers to 6/36 in the left eye. Biomicroscopy showed less exudates, hemorrhages,
and microaneurysms. Optical coherence tomography revealed reduced central retinal
thickness in both eyes after 1-3 intravitreal aflibercept injections. CONCLUSION:
Intravitreal aflibercept should be regarded a safe and effective treatment in
patients with recalcitrant macular edema due to radiation maculopathy.
PMID- 28413403
TI - Two Cases of Proliferative Diabetic Retinopathy with Marked Sheathing of the
Retinal Arteries following Vitrectomy.
AB - PURPOSE: The aim of this paper was to report 2 patients (3 eyes) with
proliferative diabetic retinopathy (PDR) who showed marked sheathing of the
retinal arterioles that was ultimately attributed to calcification following
vitrectomy. CASES: Case 1 involved a 65-year-old female with PDR who underwent
bilateral vitrectomy for traction retinal detachment. Postoperatively, bilateral
retinal redetachment (reRD) was observed. Sheathing of the retinal arterioles was
observed at the same time, yet was not apparent preoperatively. Case 2 involved a
71-year-old female with PDR who underwent vitrectomy for vitreous hemorrhage.
Postoperatively, reRD was observed, and fundus findings showed sheathing of the
retinal arterioles. In both patients, silicone oil tamponade and retinopexy were
performed at reoperation, but sheathing of the retinal arterioles persisted
postoperatively. Fluorescein fundus angiography showed that retinal blood flow
was maintained, and no vessel leakage occurred. In addition, no sheathing of the
retinal veins was observed. Optical coherence tomography (OCT) showed a higher
intensity for retinal arterioles with sheathing than for normal retinal
arterioles. CONCLUSION: Vessel sheathing in our 2 patients (3 eyes) differed from
the sheathing seen in vasculitis. Based on the hyperintensity on OCT, this
sheathing may have been due to retinal artery calcification induced by hypoxia
and inflammation associated with reRD.
PMID- 28413406
TI - A Change in Ocular Circulation after Photocoagulation for Retinopathy of
Prematurity in a Neonate.
AB - BACKGROUND: The dilation of veins and tortuosity of arteries that occur in
retinopathy of prematurity (ROP) are improved by therapy, and thus posttherapy
changes in ocular circulation are also conceivable. We report a case of ROP in
which we were able to measure the ocular circulation before and after
photocoagulation therapy, using a laser speckle flowgraphy (LSFG) system that is
modified for neonates. CASE REPORT: A female infant was born at 25 weeks'
gestation with a birth weight of 808 g. We performed photocoagulation in both
eyes at age 15 weeks, and we measured the ocular circulation with the "LSFG-baby"
system before and at 12 weeks after the photocoagulation treatment. We also
measured the mean blur rate (MBR) in the optic nerve head (ONH) and the relative
flow volume (RFV) in the retinal vessels, and we examined the change rates from
before to after treatment. The changing rate of the MBR-A (the mean of all
values) in the ONH in the right and left eyes was 76.5 and 98.5%, respectively.
The vascular RFV in the severe dilation and tortuosity quadrant also tended to
decrease. CONCLUSIONS: Photocoagulation improved the dilation of veins and
tortuosity of arteries and reduced the ocular blood flow in this neonate with
ROP. The LSFG-baby system effectively and directly revealed the optic nerve and
retinal blood vessels.
PMID- 28413407
TI - Ophthalmia Secondary to Cobra Venom Spitting in the Volta Region, Ghana: A Case
Report.
AB - PURPOSE: To report the first case of ophthalmia due to contact with cobra venom
in the Volta Region, Ghana. METHODS: An ointment containing vitamin A was applied
to treat the patient's unilateral defects in the corneal epithelium and the
consequent diminished visual acuity. RESULTS: Healing of the corneal epithelium
and improvement of visual acuity were observed after only 1 day. CONCLUSIONS:
This case suggests that consequences of cases of cobra venom spitting in the eyes
can be minimal if immediate treatment is provided.
PMID- 28413408
TI - Choroidal Nevus-Associated Neovascular Membrane Demonstrated by OCT Angiography.
AB - We present a case of choroidal nevus, complicated by a choroidal neovascular
membrane (CNV) that was detected by OCT angiography. Choroidal nevi are
relatively common intraocular tumors. The presence of subretinal and intraretinal
fluids can indicate that a CNV has occurred as a complication, warranting prompt
management. However, subretinal and intraretinal fluids are also documented in
nevi without CNV. OCT angiography may be of great help in determining whether
those fluids are associated or not with a CNV, therefore guiding therapy.
PMID- 28413409
TI - Self-Optical Coherence Tomography and Angiography.
AB - PURPOSE: To present a new concept of self-optical coherence tomography (OCT) and
self-OCT angiography. METHODS: The operator sits in the patient seat and
manipulates the instrument body via the joystick with the dominant hand, while
the dominant index is ready to press the capture button and while focusing on the
fixation target. One senior ophthalmologist judged various OCT machines for ease
of self-scan during a major ophthalmic convention. Separately, self-scans were
also captured using a single OCT machine by one senior ophthalmologist and 5
junior optometrists and the scans were analyzed for both centration and image
quality value (IQV), and compared to regular scans done by an operator. RESULTS:
Ten available OCT machines were tested for their ability to allow self-OCT.
Machines that had one or more features of auto-alignment, auto-focus, and auto
shoot were ideal for self-OCT or self-OCT angiography. Self-scans done by the
ophthalmologist (total 27 scans of right eye, mean IQV = 32.6, and 24 left eyes,
mean IQV = 37.3, done over 9 months) and 5 optometrists (total 24 scans, mean
34.8 done in one session) were comparable to scans (total 11, mean IQV = 38.1)
done by an operator for image quality. Decentration was very common in self-scans
of the macula (37% right eye and 46% left eye) versus 0% for scans of the right
eye done by an operator. CONCLUSIONS: Self-OCT scans of the macular region can be
done with good image quality but are often decentered. Advantages include
privacy, potential use by ophthalmic health professionals, airspace station
officers, and possible future home self-imaging of macula.
PMID- 28413410
TI - Eccentric Macular Hole after Pars Plana Vitrectomy for Idiopathic Macular Hole: A
Case Report.
AB - INTRODUCTION: Postoperative eccentric macular hole (MH) formation is an uncommon
complication after pars plana vitrectomy (PPV) with internal limiting membrane
(ILM) peeling for epiretinal membrane or MH treatment. Herein, we present a case
of eccentric MH formation after PPV with ILM peeling for MH. CASE DESCRIPTION: A
72-year-old female patient underwent 23-gauge PPV with ILM peeling for idiopathic
MH in her right eye. The visual acuity was 6/24 in the right eye. One week
postoperatively the retina was attached and the MH seemed to be closed, while
visual acuity was 6/12. One month after PPV, there was a single eccentric retinal
hole below the macula, which was detected at the fundoscopy and was confirmed by
OCT. The visual acuity was 6/9 and the patient referred no symptoms. No further
intervention was attempted, and at the 6-month follow-up the visual acuity and
the size of the eccentric MH remained stable. CONCLUSIONS: Eccentric MHs can
develop after PPV and are usually managed conservatively by observation.
PMID- 28413411
TI - Corrigendum: The Hog1 MAP Kinase Promotes the Recovery from Cell Cycle Arrest
Induced by Hydrogen Peroxide in Candida albicans.
AB - [This corrects the article on p. 2133 in vol. 7, PMID: 28111572.].
PMID- 28413412
TI - Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory
Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.
AB - BACKGROUND/AIMS: In the quest for prevention or treatment, there is a need to
find early markers for preclinical dementia. This study observed memory clinic
patients with subjective cognitive impairment (SCI) and normal cognitive function
at baseline. The primary aim was to address SCI as a potential risk factor for
cognitive decline. The secondary aim was to address a potential relation between
(1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory
performance over the first 2 years of follow-up, with a possible cognitive
decline after 6 years. METHODS: Eighty-one patients (mean age 61 years) were
recruited from university memory clinics and followed up for 6 years. RESULTS:
Eighty-six percent of the cohort remained cognitively stable or improved, 9%
developed mild cognitive impairment, and only 5% (n = 4) developed dementia.
Regression analysis revealed that low levels of Abeta42 at baseline and memory
decline during the first 2 years predicted dementia. When combined, these
variables were associated with a 50% risk of developing dementia. CONCLUSIONS:
Cognitive stability for 86% of the cohort suggests that SCI is predominantly a
benign condition with regard to neuropathology. The low number of individuals who
developed dementia limits the generalizability of the results and discussion of
progression factors.
PMID- 28413413
TI - The Risk of Incident Mild Cognitive Impairment and Progression to Dementia
Considering Mild Cognitive Impairment Subtypes.
AB - BACKGROUND: It remains unclear how demographic and clinical characteristics are
related to the risk of incident mild cognitive impairment (MCI) by its subtypes.
Moreover, the contribution of the subtypes of incident MCI to the progression to
dementia remains puzzling. METHODS: We used data collected by the National
Alzheimer Coordinating Center. Our analysis sample included cognitively normal
subjects at baseline. The associations were examined using competing-risks
survival regression models and Cox proportional hazards models. RESULTS: About
16.3% of subjects developed incident MCI of whom 15.8% progressed to Alz-heimer
disease (overall mean follow-up of 4.3 years). The risk of incident amnestic MCI
(aMCI) was greater in subjects with 1 copy (subhazard ratio [SHR]: 1.23; 95% CI:
1.00-1.50) or 2 copies (SHR: 2.14; 95% CI: 1.49-3.05) of the APOE epsilon4 allele
than in those who had no epsilon4 allele. Multiple-domain aMCI patients were more
likely to progress to dementia than single-domain aMCI patients (hazard ratio:
2.14; 95% CI: 1.28-3.58). CONCLUSIONS: Cognitively normal subjects with an APOE
epsilon4 allele had a higher likelihood of developing aMCI and the MCI subtype
was associated with the dementia subtype. Our findings provide important
information about practical indicators for the prediction of cognitive decline.
PMID- 28413414
TI - Comedication and Treatment Length in Users of Acetylcholinesterase Inhibitors.
AB - BACKGROUND/AIMS: Reduced clinical effect on cognitive decline in dementia by
acetylcholinesterase inhibitors (AChEIs) may be due to concurrent use of drugs
with anticholinergic properties. The aim was to analyze the incidence of AChEI
use and comedication with drugs with anticholinergic properties and other
potential unfavorable effects. METHODS: A prospective study applying drug use
data from the Norwegian Prescription Database. Anticholinergic Drug Scale (ADS)
scores were used as a measure of overall anticholinergic burden. RESULTS:
Patients with high ADS scores were more frequently discontinuing treatment early.
Coprescribing of antipsychotics was strongly associated with early
discontinuation of AChEI treatment. CONCLUSION: Coprescribing with potentially
unfavorable medications was common. A high ADS score was associated with early
discontinuation of treatment.
PMID- 28413415
TI - Effects of Nursing Home Residency on Diabetes Care in Individuals with Dementia:
An Explorative Analysis Based on German Claims Data.
AB - AIMS: This claims data-based study compares the intensity of diabetes care in
community dwellers and nursing home residents with dementia. METHODS: Delivery of
diabetes-related medical examinations (DRMEs) was compared via logistic
regression in 1,604 community dwellers and 1,010 nursing home residents with
dementia. The intra-individual effect of nursing home transfer was evaluated
within mixed models. RESULTS: Delivery of DRMEs decreases with increasing care
dependency, with more community-living individuals receiving DRMEs. Moreover,
DRME provision decreases after nursing home transfer. CONCLUSION: Dementia
patients receive fewer DRMEs than recommended, especially in cases of higher care
dependency and particularly in nursing homes. This suggests lacking awareness
regarding the specific challenges of combined diabetes and dementia care.
PMID- 28413416
TI - Immunohistochemical Glomerular Expression of Phospholipase A2 Receptor in Primary
and Secondary Membranous Nephropathy: A Retrospective Study in an Indian Cohort
with Clinicopathological Correlations.
AB - BACKGROUND: Limited published literature exists on the utility and
standardization of anti-phospholipase A2 receptor (anti-PLA2R)
immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy
(MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN
and clinicopathological correlations in an Indian cohort. METHODS: Subjects
included patients with primary and secondary MN diagnosed between January 2012
and August 2014 with an adequate renal biopsy and at least 1 year of clinical
follow-up. Anti-PLA2R IHC was performed in all cases with miscellaneous renal
lesions as controls. Electron microscopy was performed in selected cases.
Sensitivity and specificity of anti-PLA2R IHC to identify primary MN was
evaluated. Histopathological analyses of primary and secondary MN were done with
clinicopathological correlations including serum creatinine, eGFR, chronic kidney
disease stage, 24-h urine protein, serum cholesterol, serum albumin, and
hypertension at presentation and follow-up, using the Kruskal-Wallis test and
Spearman rank correlation. A p value of <=0.05 was considered statistically
significant. RESULTS: In 153 MN patients (99 primary, 54 secondary) and 37
miscellaneous controls, anti-PLA2R IHC differentiated primary from secondary MN
with a sensitivity of 70.2% and a specificity of 96.6%. Secondary MN had
increased mesangial matrix expansion compared to primary MN (p = 0.001). Severe
nephrotic syndrome, impaired renal function, and hypertension were all more
common in primary than in secondary MN. CONCLUSION: Anti-PLA2R IHC is a specific
marker to distinguish primary MN from secondary MN.
PMID- 28413417
TI - The Dialysis Sodium Gradient: A Modifiable Risk Factor for Fluid Overload.
AB - BACKGROUND: Fluid overload in patients on conventional hemodialysis is a frequent
complication, associated with increased cardiovascular morbidity and mortality.
The dialysate sodium prescription is a potential modifiable risk factor. Our
primary objective was to describe associations between dialysate-to-serum sodium
gradient and parameters of fluid status. A secondary objective was to evaluate
the 6-month risk of hospitalization and mortality in relation to sodium gradient.
METHODS: We performed a cross-sectional study of 110 prevalent conventional
hemodialysis patients at a single center. The associations of sodium gradient
with interdialytic weight gain index (IDWG%), ultrafiltration (UF) rate, and
blood pressure (BP) were analyzed. RESULTS: The mean serum sodium gradient was
4.6 +/- 3.6 mEq/L. There was a direct correlation between sodium gradient and
IDWG% (r = 0.48, p < 0.01) as well as UF rate (r = 0.44, p < 0.01). In a logistic
regression model, a 1 mEq/L higher sodium gradient was associated with increased
risk of IDWG% >3% (OR 1.33, p < 0.01) and increased risk of UF rate >10 mL/kg/h
(OR 1.16, p = 0.03), but there were no associations with intradialytic
hypotension, intradialytic hypertension or BP. No significant differences were
found with 6-month hospitalization or mortality risk in relation to sodium
gradient. CONCLUSION: A higher sodium gradient was associated with significant
increases in IDWG and UF rates, known to be associated with poor outcomes, but
was not associated with intradialytic hypotension. Individualizing the dialysate
sodium prescription to minimize sodium gap may lead to less fluid overload in
conventional hemodialysis patients.
PMID- 28413418
TI - Study of the regulatory promoter polymorphism (-938C>A) of B-cell lymphoma 2 gene
in breast cancer patients of Mazandaran province in Northern Iran.
AB - BACKGROUND: The incidence rate of breast cancer has been dramatically increasing
since the last decade in Iran, and it is now one of the most common female
malignant tumors. B-cell lymphoma 2 (BCL2) family is the most important regulator
of apoptosis, and -938C>A single nucleotide polymorphism (SNP) of BCL2 gene
promoter has been demonstrated to influence breast cancer susceptibility. In this
research, we study the effect of -938C>A allelic variants on breast cancer risk
in Mazandaran province at the North of Iran. MATERIALS AND METHODS: This analysis
performed on 120 breast cancer patients who underwent surgery in some referenced
hospitals at Mazandaran province along with 130 healthy individuals as a control.
DNA extracted from peripheral blood samples was applied in polymerase chain
reaction-single-strand conformation polymorphism analysis to determine -938C>A
genotype. The association of the -938C>A genotype and breast cancer risk as well
as clinicopathological characters were analyzed by logistic regression method.
RESULTS: Results showed that genotype frequency of AA, AC, and CC genotypes was
10%, 62%, and 28% for case and 28%, 50%, and 22% in control group, respectively.
In the logistic regression model, BCL2 - 938C/A variant genotype AA was
associated with a decreased risk of breast cancer (P = 0.041) by 0.31-fold (odds
ratio = 0.31, confidence interval = 0.091-0.909) compared to CC genotype.
However, no significant association found between -938C>A genotype and
clinicopathological characters. CONCLUSION: The study showed that AA genotype of
BCL2 gene (-938C>A) is associated with decreased susceptibility to breast cancer.
Hence, investigating the -938C>A SNP of BCL2 gene promoter could be an
appropriate molecular marker to determine individual sensitivity to breast
cancer.
PMID- 28413419
TI - Role of Vitamin D on glycemic control and oxidative stress in type 2 diabetes
mellitus.
AB - BACKGROUND: Vitamin D deficiency may play a key role in the development of
impaired glucose tolerance, type 2 diabetes mellitus (T2DM), and metabolic
syndrome. Several studies have shown that Vitamin D has an antioxidant property.
We aimed to investigate 25-hydroxy Vitamin D (25[OH]D) levels in patients with
T2DM and in nondiabetic healthy controls and to ascertain the impact of 25(OH)D
levels on glycemic control and oxidative stress in T2DM patients. MATERIALS AND
METHODS: Thirty male patients with T2DM and twenty age- and socioeconomic status
matched male healthy controls were included in the study. Fasting and
postprandial blood sugar and glycated hemoglobin (HbA1c) were measured. Enzyme
activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) was
determined by spectrophotometric assay, and serum levels of 25(OH)D were measured
using radioimmunoassay. RESULTS: Serum Vitamin D levels were significantly lower
in patients with T2DM than healthy controls (P = 0.015). There was a
significantly lower GPx activity in patients with T2DM than controls (P = 0.048),
but the difference in SOD activity did not reach statistical significance. There
was a significant negative correlation between serum Vitamin D levels and HbA1c
(P = 0.016), but no statistical correlation was shown between serum Vitamin D
levels and GPx and SOD. CONCLUSION: We conclude that low level of Vitamin D might
play a significant role in T2DM pathogenesis. Hence, Vitamin D supplementation
may improve glycemic control and oxidative stress in T2DM.
PMID- 28413420
TI - Overcrowding in emergency departments: A review of strategies to decrease future
challenges.
AB - Emergency departments (EDs) are the most challenging ward with respect to patient
delay. The goal of this study is to present strategies that have proven to reduce
delay and overcrowding in EDs. In this review article, initial electronic
database search resulted in a total of 1006 articles. Thirty articles were
included after reviewing full texts. Inclusion criteria were assessments of real
patient flows and implementing strategies inside the hospitals. In this study, we
discussed strategies of team triage, point-of-care testing, ideal ED patient
journey models, streaming, and fast track. Patients might be directed to
different streaming channels depending on clinical status and required
practitioners. The most comprehensive strategy is ideal ED patient journey
models, in which ten interrelated substrategies are provided. ED leaders should
apply strategies that provide a continuous care process without deeply depending
on external services.
PMID- 28413422
TI - Anesthetic approach to Niemann-Pick Type C patient for dental treatment.
PMID- 28413421
TI - The effect of Vitamin D and calcium plus Vitamin D on leg cramps in pregnant
women: A randomized controlled trial.
AB - BACKGROUND: This study intended to determine the effects of Vitamin D and calcium
Vitamin D in treating leg cramps in pregnant women. MATERIALS AND METHODS: This
study was conducted as a double-blind randomized controlled clinical trial on 126
participants, 18-35-year-old pregnant women with a minimum of two leg cramps per
week who were referred to health-care centers in Tabriz-Iran in 2013. The
participants were allocated to three 42 member groups using a randomized block
design. For 42 days, the intervention groups took a 1000 unit Vitamin D pill or
300 mg calcium carbonate plus a 1000 unit Vitamin D pill, and the control group
received a placebo pill every day. The participants were evaluated with regard to
the frequency, length, and pain intensity of leg cramps during the week before
and during the 3rd and 6th week of the intervention. The ANCOVA and repeated
measurement test were used to analyze the data. RESULTS: Results showed that
controlling for the effects before the intervention, calcium-Vitamin D, and
Vitamin D supplements had no effect on the frequency, length, and pain intensity
of leg cramps. CONCLUSION: The results of this study showed that the calcium
Vitamin D and the Vitamin D supplements have no effect on the frequency, length,
and pain intensity of leg cramps during the 6 weeks of the study.
PMID- 28413423
TI - Preconception care: A pragmatic approach for planned pregnancy.
PMID- 28413425
TI - Association of retinol-binding protein 4 with metabolic syndrome in first-degree
relatives of type 2 diabetic patients.
AB - BACKGROUND: Retinol-binding protein 4 (RBP4) is known to regulate lipid and
glucose metabolism and insulin resistance. The influences of RBP4 on metabolic
syndrome (MS) are still unclear. The purpose of this study is to evaluate the
association between serum levels of RBP4 and MS components in first-degree
relations of type 2 diabetic patients. MATERIALS AND METHODS: This cross
sectional study was performed within the framework of the diabetes prevention
project in Isfahan. This study has been conducted during 2012-2013. Seventy-eight
subjects participate, with an average age of 43.20 +/- 5.29 years. Weight,
height, waist and hip circumferences, blood pressure (BP) of participants,
fasting plasma glucose, hemoglobin A1c, total cholesterol, high-density
lipoprotein cholesterol, triglyceride (TG), and serum RBP4 were measured from
fasting blood sample taken from each participant after an overnight fast (12-14
h). RESULTS: Systolic and diastolic BP were significantly higher in people in top
median of RBP4 (11.8 +/- 1.5 vs. 11.0 +/- 1.2, P = 0.01 and 7.8 +/- 1.0 vs. 7.3
+/- 0.9, P = 0.03). Moreover, TG in people with high levels of RBP4 was higher
compared with those with low levels of RBP4 (177.7 +/- 97.6 vs. 138.7 +/- 56.9, P
= 0.02). People with low levels of RBP4 had significant greater hip
circumferences (107.9 +/- 7.5 vs. 104.3 +/- 8.0, P = 0.04). There was no
correlation between RBP4 and MS in crude model (odds ratio [OR]: 1.00, 0.95-1.05,
P = 0.97). This null correlation remained after adjustment for body mass index,
age, and physical activity (OR: 0.93, 0.91-1.07, P = 0.31). CONCLUSION: Although
RBP4 levels were positively association with some risk factors of MS including
hip circumference, TG, and systolic and diastolic BP, it does not seem to be a
valuable marker for identification of the MS in the first relative degree of
diabetic patients.
PMID- 28413426
TI - An inter-professional approach to personalized medicine education: one
institution's experience.
AB - Personalized medicine offers the promise of better diagnoses, targeted therapies
and individualized treatment plans. Pharmacogenomics is an integral component of
personalized medicine; it aids in the prediction of an individual's response to
medications. Despite growing public acceptance and emerging clinical evidence,
this rapidly expanding field of medicine is slow to be adopted and utilized by
healthcare providers, although many believe that they should be knowledgeable and
able to apply pharmacogenomics in clinical practice. Institutional infrastructure
must be built to support pharmacogenomic implementation. Multidisciplinary
education for healthcare providers is a critical component for pharmacogenomics
to achieve its full potential to optimize patient care. We describe our recent
experience at the Mayo Clinic implementing pharmacogenomics education in a large,
academic healthcare system facilitated by the Mayo Clinic Center for
Individualized Medicine.
PMID- 28413424
TI - Environmental factors influencing the risk of autism.
AB - Autism is a developmental disability with age of onset in childhood (under 3
years old), which is characterized by definite impairments in social
interactions, abnormalities in speech, and stereotyped pattern of behaviors. Due
to the progress of autism in recent decades, a wide range of studies have been
done to identify the etiological factors of autism. It has been found that
genetic and environmental factors are both involved in autism pathogenesis.
Hence, in this review article, a set of environmental factors involved in the
occurrence of autism has been collected, and finally, some practical
recommendations for reduction of the risk of this devastating disease in children
are represented.
PMID- 28413427
TI - Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F)
nanoparticle vaccine in older adults.
AB - BACKGROUND: A preventative strategy for Respiratory Syncytial Virus (RSV)
infection constitutes an under-recognized unmet medical need among older adults.
Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 MUg
RSV F protein, with or without aluminum phosphate adjuvant) administered
concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in
older adult subjects were evaluated for safety and immunogenicity in this
randomized, observer-blinded study. RESULTS: A total of 220 healthy males and
females >= 60 years of age, without symptomatic cardiopulmonary disease, were
vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine
formulations produced an acceptable safety profile, with no vaccine-related
serious adverse events or evidence of systemic toxicity. Vaccine-induced immune
responses were rapid, rising as early as 7 days post-vaccination; and were
comparable in all formulations in terms of magnitude, with maximal levels
attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak
anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect
observed at the 60 MUg dose, and a dose-effect observed between the unadjuvanted
60 and 90 MUg regimens. The anti-F response persisted through 12 months post
vaccination. Palivizumab-competitive antibodies were below quantifiable levels
(<33 MUg/mL) at day 0. The rise of antibodies with specificity for Site II
peptide, and the palivizumab-competitive binding activity, denoting antibodies
binding at, or in proximity to, antigenic Site II on the F protein, closely
paralleled the anti-F response. However, a larger proportion of antibodies in
adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0
neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in
response to vaccination. Importantly, the RSV F vaccine co-administered with TIV
did not impact the serum hemagglutination inhibition antibody responses to a
standard-dose TIV, and TIV did not impact the immune response to the RSV F
vaccine. CONCLUSIONS: RSV F protein nanoparticle vaccine induced increases in
measures of functional immunity to RSV in older adults and demonstrated an
acceptable safety profile. Adjuvanted formulations provided additional
immunogenicity benefit as compared to increasing antigen dose alone. This trial
was registered with ClinicalTrials.gov number NCT01709019.
PMID- 28413428
TI - Transcriptomic evidence of a para-inflammatory state in the middle aged lumbar
spinal cord.
AB - BACKGROUND: We have previously reported elevated expression of multiple pro
inflammatory markers in the lumbar spinal cord (LSC) of middle-aged male rats
compared to young adults suggesting a para-inflammatory state develops in the LSC
by middle age, a time that in humans is associated with the greatest pain
prevalence and persistence. The goal of the current study was to examine the
transcriptome-wide gene expression differences between young and middle aged LSC.
METHODS: Young (3 month) and middle-aged (17 month) naive Fisher 344 rats (n = 5
per group) were euthanized, perfused with heparinized saline, and the LSC were
removed. RESULTS: ~70% of 31,000 coding sequences were detected. After
normalization, ~ 1100 showed statistically significant differential expression.
Of these genes, 353 middle-aged annotated genes differed by > 1.5 fold compared
to the young group. Nearly 10% of these genes belonged to the microglial sensome.
Analysis of this subset revealed that the principal age-related differential
pathways populated are complement, pattern recognition receptors, OX40, and
various T cell regulatory pathways consistent with microglial priming and T cell
invasion and modulation. Many of these pathways substantially overlap those
previously identified in studies of LSC of young animals with chronic
inflammatory or neuropathic pain. CONCLUSIONS: Up-modulation of complement
pathway, microglial priming and activation, and T cell/antigen-presenting cell
communication in healthy middle-aged LSC was found. Taken together with our
previous work, the results support our conclusion that an incipient or para
inflammatory state develops in the LSC in healthy middle-aged adults.
PMID- 28413429
TI - Falling under the umbrella cells: A single institutional experience and
literature review of urothelial carcinoma presenting as a primary pancreatic mass
on endoscopic ultrasound-guided fine-needle aspiration.
AB - Metastases to the pancreas are much less common than primary pancreatic lesions,
and there are few reports in the literature of metastatic urothelial carcinoma
(UC) found in the pancreas. We report two cases of metastatic UC mimicking a
primary pancreatic lesion. Two female patients, aged 48 and 83 years, presented
with isolated pancreatic lesions causing obstructive jaundice suspicious for
pancreatic adenocarcinoma and underwent endoscopic ultrasound-guided fine-needle
aspiration (EUS-FNA) with rapid on-site evaluation (ROSE). On cytopathology, the
lesions were found to be UC, confirmed with immunohistochemical (IHC) staining.
UC rarely metastasizes to the pancreas, and diagnosis through EUS-FNA can be
challenging. However, the utilization of ROSE, dedicated cell block passes, and
IHC have proved to be effective in obtaining this unusual pancreatic diagnosis by
EUS-FNA.
PMID- 28413430
TI - Next-generation sequencing of non-small cell lung cancer using a customized,
targeted sequencing panel: Emphasis on small biopsy and cytology.
AB - BACKGROUND: Next-generation sequencing (NGS) with a multi-gene panel is now
available for patients with lung adenocarcinoma, but the performance
characteristics and clinical utility of this testing are not well-described. We
present the results of an extended 467 gene panel in a series of advanced, highly
selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens,
including predominantly small biopsy and cytology specimens. MATERIALS AND
METHODS: A retrospective review of 22 NSCLC biopsies sent for NGS using an
extended gene panel from January 2014 to July 2015. The customized NGS panel
sequences 467 cancer-associated genes with exonic and intronic sequences obtained
from purified tumor DNA. Genomic alterations, patient characteristics, and
success of testing were determined. RESULTS: The majority of samples tested were
metastatic lung adenocarcinoma on final pathology. Of the 22 specimens tested, 5
(22.7%) were surgical resections and 17 (77.3%) were small biopsy and cytology
specimens. Twenty-one (95%) of the specimens were adequate for full sequencing
and yielded a total of 204 genomic alterations (average 8.9 per tumor), of which
17 (average 0.81 per tumor) were actionable and/or clinically relevant. Genomic
alterations were found most commonly in the TP53, EGFR, EPHB1, MLL3, APC, SETD2,
KRAS, DNMT3A, RB1, CDKN2A, ARID1A, EP300, KDM6B, RAD50, STK11, and BRCA2 genes.
CONCLUSIONS: NGS using a comprehensive gene panel was performed successfully in
95% of all NSCLC cases in this series, including 94% small biopsy and cytology
specimens and 100% surgical resections. This custom assay was performed on a
range of tumor specimens and demonstrates that small specimens are able to
provide a similar depth of information as larger ones. As many patients present
at an advanced stage and only small specimens are obtained, the information these
provide has the potential for guiding treatment in highly selected patients with
advanced lung adenocarcinoma.
PMID- 28413432
TI - Resveratrol regulates body weight in healthy and ovariectomized rats.
AB - OBJECTIVE: The elevated body weight in post-menopausal state attributes to the
reduced estrogen levels which is alleviated by resveratrol (RES) but its role in
control rats is not well understood. The main objective of the study was to
explore the effects of RES on the body weight of ovariectomized (OVX) female rats
with controls and to relate their biochemical parameters. METHODS: Female Wistar
rats weighing 200-300 g underwent bilateral ovariectomy (OVX) and were fed soya
free diet (n = 8 rats per group). In all groups: (Control, Control + Resveratrol,
OVX and OVX + Resveratrol) resveratrol was administered orally at a dose of 5
mg/kg/day for 1 month. Glucose and other biochemical parameters were examined.
RESULTS: Significant reduction in the gain of body weight was observed in the
control rats treated with resveratrol. Ovariectomy caused an escalation in gain
of body weight due to loss of estrogen which was brought down with resveratrol.
There was a slight dip in the blood glucose levels after resveratrol treatment.
CONCLUSION: Resveratrol significantly reduced the gain of body weight in the
control rats and in OVX rats showing its antiobesogenic effects.
PMID- 28413431
TI - Asian house rats may facilitate their invasive success through suppressing brown
rats in chronic interaction.
AB - BACKGROUND: The Asian house rat (Rattus tanezumi) and the brown rat (Rattus
norvegicus) are closely related species and are partially sympatric in southern
China. Over the past 20 years, R. tanezumi has significantly expanded northward
in China and partially replaced the native brown rat subspecies, R. n.
humiliatus. Although invasive species are often more aggressive than native
species, we did not observe interspecific physical aggression between R. tanezumi
and R. n. humiliatus. Here, we focused on whether or not R. tanezumi was superior
to R. n. humiliatus in terms of nonphysical competition, which is primarily
mediated by chemical signals. RESULTS: We performed two laboratory experiments to
test different paradigms in domesticated R. tanezumi and R. n. humiliatus. In
Experiment 1, we caged adult male rats of each species for 2 months in
heterospecific or conspecific pairs, partitioned by perforated galvanized iron
sheets, allowing exchange of chemical stimuli and ultrasonic vocalization. The
sexual attractiveness of male urine odor showed a tendency (marginal
significance) to increase in R. tanezumi caged with R. n. humiliatus, compared
with those in conspecific pairs. Hippocampal glucocorticoid receptor (GR) and
brain-derived nutrition factor (BDNF) mRNA were upregulated in R. n. humiliatus
and R. tanezumi, respectively, when the rats were caged in heterospecific pairs.
In Experiment 2, we kept juvenile male rats in individual cages in rooms with
either the same or the different species for 2 months, allowing chemical
interaction. The sexual attractiveness of male urine was significantly enhanced
in R. tanezumi, but reduced in R. n. humiliatus by heterospecific cues and mRNA
expression of hippocampal GR and BDNF were upregulated by heterospecific cues in
R. n. humiliatus and R. tanezumi, respectively. Although not identical, the
results from Experiments 1 and 2 were generally consistent. CONCLUSIONS: The
results of both experiments indicate that nonphysical/chronic interspecific
stimuli, particularly scent signals, between R. n. humiliatus and R. tanezumi may
negatively affect R. n. humiliatus and positively affect R. tanezumi. We infer
that chronic interspecific interactions may have contributed to the invasion of
R. tanezumi into the range of R. n. humiliatus in natural habitats.
PMID- 28413433
TI - Protoplast isolation prior to flow cytometry reveals clear patterns of
endoreduplication in potato tubers, related species, and some starchy root crops.
AB - BACKGROUND: Endoreduplication, the process of DNA replication in the absence of
cell division, is associated with specialized cellular function and increased
cell size. Genes controlling endoreduplication in tomato fruit have been shown to
affect mature fruit size. An efficient method of estimating endoreduplication is
required to study its role in plant organ development. Flow cytometry is often
utilized to evaluate endoreduplication, yet some tissues and species, among them
the tubers of Solanum tuberosum, remain intractable to routine tissue preparation
for flow cytometry. We aimed to develop a method through the use of protoplast
extraction preceding flow cytometry, specifically for the assessment of
endoreduplication in potato tubers. RESULTS: We present a method for appraising
endoreduplication in potato (Solanum tuberosum) tuber tissues. We evaluated this
method and observed consistent differences between pith and cortex of tubers and
between different cultivars, but no apparent relationship with whole tuber size.
Furthermore, we were able to observe distinct patterns of endoreduplication in 16
of 20 wild potato relatives, with mean endoreduplication index (EI) ranging from
0.94 to 2.62 endocycles per cell. The protocol was also applied to a panel of
starchy root crop species and, while only two of five yielded reliable flow
histograms, the two (sweet potato and turnip) exhibited substantially lower EIs
than wild and cultivated potato accessions. CONCLUSIONS: The protocol reported
herein has proven effective on tubers of a variety of potato cultivars and
related species, as well as storage roots of other starchy crops. This method
provides an important tool for the study of potato morphology and development
while revealing natural variation for endoreduplication which may have
agricultural relevance.
PMID- 28413434
TI - Multicolour localization microscopy by point-spread-function engineering.
AB - Super-resolution microscopy has revolutionized cellular imaging in recent years1
4. Methods relying on sequential localization of single point emitters enable
spatial tracking at ~10-40 nm resolution. Moreover, tracking and imaging in three
dimensions is made possible by various techniques, including point-spread
function (PSF) engineering5-9 -namely, encoding the axial (z) position of a point
source in the shape that it creates in the image plane. However, a remaining
challenge for localization-microscopy is efficient multicolour imaging - a task
of the utmost importance for contextualizing biological data. Normally,
multicolour imaging requires sequential imaging10, 11, multiple cameras12, or
segmented dedicated fields of view13, 14. Here, we demonstrate an alternate
strategy, the encoding of spectral information (colour), in addition to 3D
position, directly in the image. By exploiting chromatic dispersion, we design a
new class of optical phase masks that simultaneously yield controllably different
PSFs for different wavelengths, enabling simultaneous multicolour tracking or
super-resolution imaging in a single optical path.
PMID- 28413435
TI - Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from
Myanmar.
AB - BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse
mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors.
HMTV (MMTV-like) sequences were reported to be present in human breast cancers
from several populations with a prevalence range of 0-78%; however, the
prevalence of HMTV in breast cancers from Myanmar remains unknown. METHODS: Fifty
eight breast cancer samples from Myanmar women were examined in this study. DNA
was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope
sequences were detected by semi-nested PCR. The sequence of the PCR products was
also confirmed. RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive
for HMTV, and the sequence of PCR products was 98.9% identical to the reference
HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III
invasive ductal carcinoma, 7.0 cm in size with lymph node metastasis (T3, N1,
M0). CONCLUSIONS: We, for the first time, investigated the presence of HMTV in
Myanmar breast cancer patients. In accordance with other Asian studies, the
prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian
breast cancers have different etiologies than in Western countries, where HMTV is
more prevalent.
PMID- 28413436
TI - Predominance and association risk of Blastocystis hominis subtype I in colorectal
cancer: a case control study.
AB - BACKGROUND: Blastocystis, a genetically diverse intestinal parasite with
controversial pathogenic potential, has increasingly been incriminated for
diarrheal illness in immunocompromised individuals including colorectal cancer
(CRC) patients. The aim of the current study was to assess the possible
association between Blastocystis infection and CRC condition in Makkah, Saudi
Arabia (KSA). METHODS: Stool samples were collected from 80 non-cancer (NC) and
138 cancer subjects including 74 CRC patients and 64 patients with other cancers
outside gastrointestinal tract (COGT). Molecularly confirmed Blastocystis
isolates were genetically grouped and subtyped using multiplex polymerase chain
reaction with restriction fragment length polymorphism (PCR-RFLP) and sequence
tagged site primers-based PCR (PCR-STS), respectively. RESULTS: Blastocystis
hominis were confirmed in 29.7, 25 and 15% among CRC, COGT and NC patients,
respectively. Obtained Blastocystis isolates were initially categorized into 2
groups (A and C), which were subsequently subtyped into 3 different subtypes;
subtype-I (38%), subtype-II (44%) and subtype-V (22%). Interestingly, subtype-I
was the most predominantly detected subtype (54.5%) among CRC patients with a
significant association risk (COR 7.548; 95% CI: 1.629-34.987; P = 0.004).
CONCLUSION: To the best of our knowledge, the current study is the first to
provide genetic insights on the prevalence of Blastocystis hominis among CRC
patients in Makkah, KSA. Moreover, the study suggests for a possible association
between subtype-I of Blastocystis hominis and CRC, which could indicate a
potential influence of Blastocystis on CRC condition. Further studies are
required to confirm this association risk and to investigate the possible
underlying mechanism of postulated carcinogenic influence of Blastocystis hominis
subtype-I.
PMID- 28413437
TI - goSTAG: gene ontology subtrees to tag and annotate genes within a set.
AB - BACKGROUND: Over-representation analysis (ORA) detects enrichment of genes within
biological categories. Gene Ontology (GO) domains are commonly used for gene/gene
product annotation. When ORA is employed, often times there are hundreds of
statistically significant GO terms per gene set. Comparing enriched categories
between a large number of analyses and identifying the term within the GO
hierarchy with the most connections is challenging. Furthermore, ascertaining
biological themes representative of the samples can be highly subjective from the
interpretation of the enriched categories. RESULTS: We developed goSTAG for
utilizing GO Subtrees to Tag and Annotate Genes that are part of a set. Given
gene lists from microarray, RNA sequencing (RNA-Seq) or other genomic high
throughput technologies, goSTAG performs GO enrichment analysis and clusters the
GO terms based on the p-values from the significance tests. GO subtrees are
constructed for each cluster, and the term that has the most paths to the root
within the subtree is used to tag and annotate the cluster as the biological
theme. We tested goSTAG on a microarray gene expression data set of samples
acquired from the bone marrow of rats exposed to cancer therapeutic drugs to
determine whether the combination or the order of administration influenced bone
marrow toxicity at the level of gene expression. Several clusters were labeled
with GO biological processes (BPs) from the subtrees that are indicative of some
of the prominent pathways modulated in bone marrow from animals treated with an
oxaliplatin/topotecan combination. In particular, negative regulation of MAP
kinase activity was the biological theme exclusively in the cluster associated
with enrichment at 6 h after treatment with oxaliplatin followed by control.
However, nucleoside triphosphate catabolic process was the GO BP labeled
exclusively at 6 h after treatment with topotecan followed by control.
CONCLUSIONS: goSTAG converts gene lists from genomic analyses into biological
themes by enriching biological categories and constructing GO subtrees from over
represented terms in the clusters. The terms with the most paths to the root in
the subtree are used to represent the biological themes. goSTAG is developed in R
as a Bioconductor package and is available at
https://bioconductor.org/packages/goSTAG.
PMID- 28413438
TI - A case report of brief psychotic disorder with catalepsy associated with
sequential life-threatening events in a patient with advanced cancer.
AB - BACKGROUND: Cancer is commonly perceived as life-threatening and universally
stressful; however, brief psychotic disorder, which occurs in response to
extremely stressful events, has not been reported. CASE PRESENTATION: A 63-year
old woman, who was diagnosed as having pancreatic cancer with liver metastasis,
became unresponsive with very little reaction to verbal contact after sequential
life-threatening events, such as thrombosis of both pulmonary arteries and
stenosis of the third portion of the duodenum, due to disease progression over 3
weeks beginning with oncological emergency hospital admission. Laboratory
findings and electroencephalography were unremarkable. She maintained the
position when the psycho-oncologist raised her hand (catalepsy). She had no
medical history of psychiatric illness, or alcohol or drug abuse. From these
findings, she was suspected of having a brief psychotic disorder with catalepsy
and substupor, and 2.5 mg of haloperidol was administered. Her psychiatric
symptoms disappeared in 4 days and the diagnosis of brief psychotic disorder was
confirmed. CONCLUSIONS: Brief psychotic disorders can manifest in patients with
cancer. Careful clinical assessment is needed to correctly diagnose patients with
cancer who develop brief psychotic disorders and to identify those who will
benefit from correct treatment.
PMID- 28413439
TI - Family reintegration of homeless in Maputo and Matola: a descriptive study.
AB - BACKGROUND: Homelessness is a global and local social problem with underestimated
prevalence. It has been shown to increase the risk of mental illness, raising
concerns from mental health providers about the need for effective interventions
targeting this population. OBJECTIVES: The aim of this paper is to describe the
mental health status of the homeless people in two urban setting in a low-income
country, through using standardised clinical and socio-demographic assessments as
well assessing potential predictors of family integration versus non-family
integration among a group of homeless individuals receiving psychiatric and
psychosocial treatment. METHODS: A descriptive study was performed in Maputo and
Matola cities between 2008 and 2010. Homeless people with apparent mental illness
were mapped and recruited. The participants were referred from community to
hospital, using a multidisciplinary treatment model, according to their clinical
condition and later entered a family reintegration process. RESULTS: Seventy-one
homeless people were recruited (93.0% male; 80.3% unemployed). The most common
diagnosis was schizophrenia and other psychosis (46; 64.8%), followed by mental
and behaviour disorder related to substance misuse (21; 29.6%), and intellectual
disability (4; 5.6%). Family reintegration was achieved for 53.5% (38 patients).
Patients with intellectual disability were less reintegrated and those with
disorders related to substance use had better reinsertion in their families (Chi
square (2) = 6.1; p = 0.047). CONCLUSIONS: Family reintegration was achieved in
more than half of participants after hospitalization. Integration was higher in
cases of substance misuse, with those with associated intellectual disability
being more difficult to reintegrate. Trial registration Trial Registration
Number: NCT02936141, date of registration: 14/10/2016, retrospectively
registered.
PMID- 28413440
TI - Predictors of depression among patients receiving treatment for snakebite in
General Hospital, Kaltungo, Gombe State, Nigeria: August 2015.
AB - BACKGROUND: Snakebite though neglected, affects 5 million people yearly. More
neglected is the psychological effect of envenomation. We determined prevalence
and pattern of depression among patients admitted into snakebite wards of
Kaltungo General Hospital Nigeria, and percentage recognized by clinicians. We
also assessed for factors associated with depression. METHODS: In a descriptive
hospital based study, we used Patient Health questionnaire (PHQ-9) to make
diagnosis of depression among the patients. We reviewed patients' clinical
records to determine clinicians' recognition of depression. RESULTS: Of 187
interviews analyzed, 47 (25%) had depression with none recognized by attending
clinicians. Patients with snakebite complications (odd ratio [OR] 3.1, 95% CI 1.1
8.5), and previous history of snakebites (OR 2.7, 95% CI 1.1-6.1) were associated
with mild depression. Worrying about family welfare (OR 31.5, 95% CI 6.5-152.9),
financial loss (OR 14.6, 95% CI 1.8-121.5) and time loss (OR 14.6, 95% CI 1.8
121.5), past history of snakebites (OR 8.3, 95% CI 1.9-36.5) and lower income
(Mean difference -25,069 [84 USD], 95% CI 35,509 [118 USD]-14,630 [49 USD]) were
associated with severe depression. CONCLUSION: A quarter of in-patients of
snakebite wards of the general hospital had comorbid depression that went
unrecognized. Independent predictors of depression such as past history of
snakebite, worrying about relations and having snakebite complications could help
clinicians anticipate depression among patients. We recommend training of
clinicians in the hospital on recognition of common psychological disorders like
depression.
PMID- 28413441
TI - Prevalence and associated factors of attention deficit hyperactivity disorder
(ADHD) among Ugandan children; a cross-sectional study.
AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common
neuropsychiatric disorder among the children. The burden of ADHD or its
associated factors in Uganda are not known. The objective of this study was to
determine the prevalence and the associated factors of ADHD among children
attending the neurology and psychiatry clinics at Mulago National Referral
Hospital. METHODS: Using the disruptive behavior scale (45 items), we
investigated the presence of ADHD symptoms among children attending Mulago
Hospital. Questionnaires were administered to the primary care-takers of the
study participants to gather information on the factors associated with ADHD. All
children were subject to a clinical examination. Children presumed to have ADHD,
using the aforementioned rating scale were further assessed by a child
psychiatrist to confirm the diagnosis and associated co-morbid conditions.
RESULTS: The estimated prevalence of DSM-IV ADHD symptoms was 11%. Children aged
less than 10 years were four times likely to have ADHD (OR 4.1, 95% CI 1.7-9.6, p
< 0.001). The demographic factors independently associated with ADHD were age
less than 10 years, male gender, history of maternal abnormal vaginal discharge
during pregnancy, and no formal education or the highest level of education being
primary school. CONCLUSION: The prevalence of ADHD among children attending the
pediatric neurology and psychiatry clinics is high in our settings and is
associated with delayed milestones. Early identification and addressing the co
morbid conditions associated with ADHD such as epilepsy, autism spectrum of
disorder, conduct disorder, opposition defiant disorder and intellectual
disability in our setting is needed.
PMID- 28413442
TI - Specific coping strategies moderate the link between emotion expression deficits
and nonsuicidal self-injury in an inpatient sample of adolescents.
AB - BACKGROUND: Non-suicidal self-injury (NSSI) is a behavior of increasing
prevalence in adolescents with links to various negative mental health and
adjustment outcomes. Poor emotion expression has been linked with NSSI use,
whereas the use of adaptive coping strategies has been identified as a protective
factor against NSSI. The current study examined whether specific coping
strategies moderate the relation between poor emotion expression and NSSI, and
whether moderation is conditional on adolescent gender. METHODS: Ninety-five
adolescents hospitalized on an acute care inpatient psychiatric unit completed
questionnaires measuring NSSI, emotion expression and use of specific coping
strategies (i.e., problem-focused coping, positive reframing coping, support
seeking, avoidance, and distraction). RESULTS: Results indicated that poor
emotion expression was positively associated with NSSI. Positive reframing and
support seeking emerged as significant moderators of the poor emotion expression
NSSI link. This result was not conditional upon adolescent gender. Problem
focused coping, avoidance, and distraction did not emerge as significant
moderators. CONCLUSIONS: Encouraging youth to use particular coping strategies
might protect against the negative impact of emotion expression deficits for both
boys and girls.
PMID- 28413443
TI - Molecular and biochemical characterization of recombinant cel12B, cel8C, and
peh28 overexpressed in Escherichia coli and their potential in biofuel
production.
AB - BACKGROUND: The high crystallinity of cellulosic biomass myofibrils as well as
the complexity of their intermolecular structure is a significant impediment for
biofuel production. Cloning of celB-, celC-encoded cellulases (cel12B and cel8C)
and peh-encoded polygalacturonase (peh28) from Pectobacterium carotovorum subsp.
carotovorum (Pcc) was carried out in our previous study using Escherichia coli as
a host vector. The current study partially characterizes the enzymes' molecular
structures as well as their catalytic performance on different substrates which
can be used to improve their potential for lignocellulosic biomass conversion.
RESULTS: beta-Jelly roll topology, (alpha/alpha)6 antiparallel helices and right
handed beta-helices were the folds identified for cel12B, cel8C, and peh28,
respectively, in their corresponding protein model structures. Purifications of
17.4-, 6.2-, and 6.0-fold, compared to crude extract, were achieved for cel12B
and cel8C, and peh28, respectively, using specific membrane ultrafiltrations and
size-exclusion chromatography. Avicel and carboxymethyl cellulose (CMC) were
substrates for cel12B, whereas for cel8C catalytic activity was only shown on
CMC. The enzymes displayed significant synergy on CMC but not on Avicel when
tested for 3 h at 45 degrees C. No observed beta-glucosidase activities were
identified for cel8C and cel12B when tested on p-nitrophenyl-beta-d
glucopyranoside. Activity stimulation of 130% was observed when a recombinant
beta-glucosidase from Pcc was added to cel8C and cel12B as tested for 3 h at 45
degrees C. Optimum temperature and pH of 45 degrees C and 5.4, respectively,
were identified for all three enzymes using various substrates. Catalytic
efficiencies (kcat/Km) were calculated for cel12B and cel8C on CMC as 0.141 and
2.45 ml/mg/s respectively, at 45 degrees C and pH 5.0 and for peh28 on
polygalacturonic acid as 4.87 ml/mg/s, at 40 degrees C and pH 5.0. Glucose and
cellobiose were the end-products identified for cel8C, cel12B, and beta
glucosidase acting together on Avicel or CMC, while galacturonic acid and other
minor co-products were identified for peh28 action on pectin. CONCLUSIONS: This
study provides some insight into which parameters should be optimized when
application of cel8C, cel12B, and peh28 to biomass conversion is the goal.
PMID- 28413444
TI - Functional photosystem I maintains proper energy balance during nitrogen
depletion in Chlamydomonas reinhardtii, promoting triacylglycerol accumulation.
AB - BACKGROUND: Nutrient deprivation causes significant stress to the unicellular
microalga, Chlamydomonas reinhardtii, which responds by significantly altering
its metabolic program. Following N deprivation, the accumulation of starch and
triacylglycerols (TAGs) is significantly altered following massive reprogramming
of cellular metabolism. One protein that was found to change dramatically and
early to this stress was TAB2, a photosystem I (PSI) translation initiation
factor, whose transcript and protein levels increased significantly after only 30
min of N deprivation. A detailed physiological and omics-based analysis of an
insertional mutant of Chlamydomonas with reduced TAB2 function was conducted to
determine what role the functional PSI plays in regulating the cellular response
to N deprivation. RESULTS: The tab2 mutant displayed increased acetate
assimilation and elevated starch levels during the first 6 h of N deprivation,
followed by a shift toward altered amino acid synthesis, reduced TAG content and
altered fatty acid profiles. These results suggested a central role for PSI in
controlling cellular metabolism and its implication in regulation of lipid/starch
partitioning. Time course analyses of the tab2 mutant versus wild type under N
deprived versus N replete conditions revealed changes in the ATP/NADPH ratio and
suggested that TAG biosynthesis may be associated with maintaining the redox
state of the cell during N deprivation. The loss of ability to accumulate TAG in
the tab2 mutant co-occurred with an up-regulation of photo-protective mechanisms,
suggesting that the synthesis of TAG in the wild type occurs not only as a
temporal energy sink, but also as a protective electron sink. CONCLUSIONS: By
exploiting the tab2 mutation in the cells of C. reinhardtii cultured under
autotrophic, mixotrophic, and heterotrophic conditions during nitrogen replete
growth and for the first 8 days of nitrogen deprivation, we showed that TAG
accumulation and lipid/starch partitioning are dynamically regulated by
alterations in PSI function, which concomitantly alters the immediate ATP/NADPH
demand. This occurs even without removal of nitrogen from the medium, but
sufficient external carbon must nevertheless be available. Efforts to increase
lipid accumulation in algae such as Chlamydomonas need to consider carefully how
the energy balance of the cell is involved in or affected by such efforts and
that numerous layers of metabolic and genetic regulatory control are likely to
interfere with such efforts to control oil biosynthesis. Such knowledge will
enable synthetic biology approaches to alter the response to the N depletion
stress, leading to rewiring of the regulatory networks so that lipid accumulation
could be turned on in the absence of N deprivation, allowing for the development
of algal production strains with highly enhanced lipid accumulation profiles.
PMID- 28413446
TI - Artificial miRNA inhibition of phosphoenolpyruvate carboxylase increases fatty
acid production in a green microalga Chlamydomonas reinhardtii.
AB - BACKGROUND: Nutrient limitation, such as nitrogen depletion, is the most widely
used method for improving microalgae fatty acid production; however, these harsh
conditions also inhibit algal growth significantly and even kill cells at all. To
avoid these problems, we used artificial microRNA (amiRNA) technology as a useful
tool to manipulate metabolic pathways to increase fatty acid contents effectively
in the green microalga Chlamydomonas reinhardtii. We down-regulated the
expression of phosphoenolpyruvate carboxylase (PEPC), which catalyzes the
formation of oxaloacetate from phosphoenolpyruvate and regulates carbon flux.
RESULTS: amiRNAs against two CrPEPC genes were designed and transformed into
Chlamydomonas cells and amiRNAs were induced by heat shock treatment. The
transcription levels of amiRNAs increased 16-28 times, resulting in the
remarkable decreases of the expression of CrPEPCs. In the end, inhibiting the
expression of the CrPEPC genes dramatically increased the total fatty acid
content in the transgenic algae by 28.7-48.6%, which mostly increased the content
of C16-C22 fatty acids. Furthermore, the highest content was that of C18:3n3 with
an average increase of 35.75%, while C20-C22 fatty acid content significantly
increased by 85-160%. CONCLUSIONS: Overall our results suggest that heat shock
treatment induced the expression of amiRNAs, which can effectively down-regulate
the expression of CrPEPCs in C. reinhardtii, resulting in an increase of fatty
acid synthesis with the most significant increase occurring for C16 to C22 fatty
acids.
PMID- 28413445
TI - Valorization of untreated rice bran towards bioflocculant using a lignocellulose
degrading strain and its use in microalgal biomass harvest.
AB - BACKGROUND: Microalgae are currently considered as a promising feedstock for the
production of biofuels and high-value products. However, the efficient harvest of
microalgal biomasses from their culture broth is a major challenge. The
harvesting of algal biomass by flocculation combined with gravity sedimentation
is more convenient and cost-effective than traditional methods such as
centrifugation and filtration. Compared to inorganic and chemically synthetic
flocculants, bioflocculants are a suitable choice for microalgal harvest due to
their biodegradable and nontoxic properties. Nonetheless, the high production
costs associated with expensive substrates hinder the commercial applications of
bioflocculants. Previous studies have shown that the hydrolysates of
lignocellulosic biomasses from dilute acid hydrolysis can be utilized as an
inexpensive carbon source for the production of bioflocculants. However, the
toxic by-products generated in the dilute acid hydrolysis step limit the
efficiency of subsequent fermentation. The strains that produce bioflocculants by
using untreated lignocellulosic materials can circumvent the pretreatment
process, as well as promote the application of bioflocculants in microalgal
harvest. RESULTS: Under alkaline fermentation conditions, the alkaliphilic strain
Bacillus agaradhaerens C9 secreted 1.69 IU/mL of alkali-tolerant xylanase and
0.06 IU/mL of cellulase, indicating that this particular strain can efficiently
convert untreated rice bran into bioflocculant (RBBF-C9), thereby circumventing
rice bran pretreatment for downstream fermentation. The optimal fermentation
conditions that result in the highest bioflocculant yield (12.94 g/L) were as
follows: 20 g/L of untreated rice bran, 3 g/L of yeast extract, and 20 g/L of
Na2CO3 at 37 degrees C for 24 h. RBBF-C9 contained 74.12% polysaccharides and
4.51% proteins, and was estimated to be 137 kDa. Furthermore, the bioflocculant
RBBF-C9 exhibited good flocculating efficiency (91.05%) of oil alga Chlorella
minutissima UTEX2341 when 60 mg/L of RBBF-C9 was added into the algal culture
broth. CONCLUSIONS: This study demonstrated that untreated rice bran is a
suitable inexpensive substrate for the production of bioflocculants, and thus
provides a novel approach in utilizing rice bran. The extracted bioflocculants
may be potentially used in biomass harvesting of the oil algae C. minutissima
UTEX2341 from the culture broth.
PMID- 28413447
TI - Enhancement of ethanol production from green liquor-ethanol-pretreated sugarcane
bagasse by glucose-xylose cofermentation at high solid loadings with mixed
Saccharomyces cerevisiae strains.
AB - BACKGROUND: Efficient cofermentation of glucose and xylose is necessary for
economically feasible bioethanol production from lignocellulosic biomass. Here,
we demonstrate pretreatment of sugarcane bagasse (SCB) with green liquor (GL)
combined with ethanol (GL-Ethanol) by adding different GL amounts. The common
Saccharomyces cerevisiae (CSC) and thermophilic S. cerevisiae (TSC) strains were
used and different yeast cell mass ratios (CSC to TSC) were compared. The
simultaneous saccharification and cofermentation (SSF/SSCF) process was performed
by 5-20% (w/v) dry substrate (DS) solid loadings to determine optimal conditions
for the co-consumption of glucose and xylose. RESULTS: Compared to previous
studies that tested fermentation of glucose using only the CSC, we obtained
higher ethanol yield and concentration (92.80% and 23.22 g/L) with 1.5 mL GL/g-DS
GL-Ethanol-pretreated SCB at 5% (w/v) solid loading and a CSC-to-TSC yeast cell
mass ratio of 1:2 (w/w). Using 10% (w/v) solid loading under the same conditions,
the ethanol concentration increased to 42.53 g/L but the ethanol yield decreased
to 84.99%. In addition, an increase in the solid loading up to a certain point
led to an increase in the ethanol concentration from 1.5 mL GL/g-DS-pretreated
SCB. The highest ethanol concentration (68.24 g/L) was obtained with 15% (w/v)
solid loading, using a CSC-to-TSC yeast cell mass ratio of 1:3 (w/w).
CONCLUSIONS: GL-Ethanol pretreatment is a promising pretreatment method for
improving both glucan and xylan conversion efficiencies of SCB. There was a
competitive relationship between the two yeast strains, and the glucose and
xylose utilization ability of the TSC was better than that of the CSC. Ethanol
concentration was obviously increased at high solid loading, but the yield
decreased as a result of an increase in the viscosity and inhibitor levels in the
fermentation system. Finally, the SSCF of GL-Ethanol-pretreated SCB with mixed S.
cerevisiae strains increased ethanol concentration and was an effective
conversion process for ethanol production at high solid loading.
PMID- 28413448
TI - Genetic and epigenetic characterization of the tumors in a patient with a tongue
primary tumor, a recurrence and a pharyngoesophageal second primary tumor.
AB - BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or
second primary tumors remains controversial, as the treatment modalities
available might be reduced by the treatment of the first tumor, and the overall
survival is lower when compared with patients with a single or first tumor.
Identifying biomarkers that predict the risk of relapse and the response to
treatment is an emerging clinical issue. CASE PRESENTATION: A Caucasian 49-years
old man was treated with chemotherapy followed by chemoradiotherapy for a primary
left side tongue tumor, achieving a complete response. After 49-months of follow
up, a local recurrence was diagnosed. After 3 months, a second primary tumor at
the pharyngoesophageal region was detected. Genomic and epigenetic
characterization of these three tumors was performed using array Comparative
Genomic Hybridization, Multiplex Ligation-dependent Probe Amplification (MLPA)
and Methylation Specific MLPA. RESULTS: The three tumors of this patient shared
several imbalances in all chromosomes excluding chromosomes 9, 20 and 22, where
genes related to important functional mechanisms of tumorigenesis are mapped. The
shared genomic imbalances, such as losses at 1p, 2p, 3p, 4q, 5q, 6q, 7q, 8p, 10p,
11q, 12p, 12q, 13q, 15q, 16p, 16q, 17p, 17q, 18q, 19p, 19q, 21q and Xp and gains
at 3q, 7q, 14q and 15q showed a common clonal origin for the diagnosed relapses.
We identified some chromosomal imbalances and genes mapped in the chromosomes 2,
3, 4, 6, 7, 11, 14, 17, 18 and 22 as putative linked to chemoradioresistance and
chemoradiosensitivity. We also observed that gains in short arm of chromosomes 6,
7, 8 and 18 were acquired after treatment of the primary tumor. We identified
losses of VHL gene and promoter methylation of WT1 and GATA5 genes, as predictors
of relapses. CONCLUSIONS: A common clonal origin for the diagnosed relapses was
observed and we identified some putative candidate biomarkers of prognosis,
relapse risk and treatment response that could guide the development of
management strategies for these patients.
PMID- 28413449
TI - Links between DNA methylation and nucleosome occupancy in the human genome.
AB - BACKGROUND: DNA methylation is an epigenetic modification that is enriched in
heterochromatin but depleted at active promoters and enhancers. However, the
debate on whether or not DNA methylation is a reliable indicator of high
nucleosome occupancy has not been settled. For example, the methylation levels of
DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while
other studies have shown that the nucleosome core is the preferred site of
methylation. In this study, we make progress toward understanding these
conflicting phenomena by implementing a bioinformatics approach that combines
MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and
nucleosome occupancy throughout the human genome. RESULTS: The results
demonstrated that increasing methylated CpG density is correlated with nucleosome
occupancy in the total genome and within nearly all subgenomic regions. Features
with elevated methylated CpG density such as exons, SINE-Alu sequences, H3K36
trimethylated peaks, and methylated CpG islands are among the highest nucleosome
occupied elements in the genome, while some of the lowest occupancies are
displayed by unmethylated CpG islands and unmethylated transcription factor
binding sites. Additionally, outside of CpG islands, the density of CpGs within
nucleosomes was shown to be important for the nucleosomal location of DNA
methylation with low CpG frequencies favoring linker methylation and high CpG
frequencies favoring core particle methylation. Prominent exceptions to the
correlations between methylated CpG density and nucleosome occupancy include CpG
islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and
these modifications, along with DNA methylation, distinguish the major silencing
mechanisms of the human epigenome. CONCLUSIONS: Thus, the relationship between
DNA methylation and nucleosome occupancy is influenced by the density of
methylated CpG dinucleotides and by other epigenomic components in chromatin.
PMID- 28413450
TI - Fetal testis organ culture reproduces the dynamics of epigenetic reprogramming in
rat gonocytes.
AB - BACKGROUND: Epigenetic reprogramming is a critical step in male germ cell
development that occurs during perinatal life. It is characterized by the
remodeling of different epigenetic marks such as DNA methylation (5mC) and
methylation of histone H3. It has been suggested that endocrine disruptors can
affect the male germline epigenome by altering epigenetic reprogramming, but the
mechanisms involved are still unknown. We have previously used an organ culture
system that maintains the development of the different fetal testis cell types,
to evaluate the effects of various endocrine disruptors on gametogenesis and
steroidogenesis in the rat. We hypothesize that this culture model can reproduce
the epigenetic reprogramming in gonocytes. Our aim was to establish the kinetics
of three epigenetic marks throughout perinatal development in rats in vivo and
compare them after different culture times. RESULTS: Using immunofluorescence, we
showed that H3K4me2 transiently increased in gonocytes at 18.5 days post-coitum
(dpc), while H3K4me3 displayed a stable increase in gonocytes from 18.5 dpc until
after birth. 5mC progressively increased from 20.5 dpc until after birth. Using
GFP-positive gonocytes purified from GCS-EGFP rats, we established the chronology
of re-methylation of H19 and Snrpn in rat gonocytes. Most importantly, using
testis explanted at 16.5 or 18.5 dpc and cultured for 2-4 days, we demonstrated
that the kinetics of changes in H3K4me2, H3K4me3, global DNA methylation and on
parental imprints can generally be reproduced ex vivo with the model of organ
culture without the addition of serum. CONCLUSIONS: This study reveals the
chronology of three epigenetic marks (H3K4me2, H3K4me3 and 5mC) and the patterns
of methylation of H19 and Snrpn differentially methylated regions in rat
gonocytes during perinatal development. Most importantly, our results suggest
that the organ culture can reproduce the process of epigenetic reprogramming and
can be used to study the impact of environmental chemicals on the establishment
of the male germ cell epigenome.
PMID- 28413451
TI - Differential DNA methylation at conserved non-genic elements and evidence for
transgenerational inheritance following developmental exposure to mono(2
ethylhexyl) phthalate and 5-azacytidine in zebrafish.
AB - BACKGROUND: Exposure to environmental stressors during development may lead to
latent and transgenerational adverse health effects. To understand the role of
DNA methylation in these effects, we used zebrafish as a vertebrate model to
investigate heritable changes in DNA methylation following chemical-induced
stress during early development. We exposed zebrafish embryos to non-embryotoxic
concentrations of the biologically active phthalate metabolite mono(2-ethylhexyl)
phthalate (MEHP, 30 uM) and the DNA methyltransferase 1 inhibitor 5-azacytidine
(5AC, 10 uM). Direct, latent and transgenerational effects on DNA methylation
were assessed using global, genome-wide and locus-specific DNA methylation
analyses. RESULTS: Following direct exposure in zebrafish embryos from 0 to 6
days post-fertilization, genome-wide analysis revealed a multitude of
differentially methylated regions, strongly enriched at conserved non-genic
elements for both compounds. Pathways involved in adipogenesis were enriched with
the putative obesogenic compound MEHP. Exposure to 5AC resulted in enrichment of
pathways involved in embryonic development and transgenerational effects on
larval body length. Locus-specific methylation analysis of 10 differentially
methylated sites revealed six of these loci differentially methylated in sperm
sampled from adult zebrafish exposed during development to 5AC, and in first and
second generation larvae. With MEHP, consistent changes were found at 2 specific
loci in first and second generation larvae. CONCLUSIONS: Our results suggest a
functional role for DNA methylation on cis-regulatory conserved elements
following developmental exposure to compounds. Effects on these regions are
potentially transferred to subsequent generations.
PMID- 28413452
TI - Ankle and toe muscle strength characteristics in runners with a history of medial
tibial stress syndrome.
AB - BACKGROUND: A high proportion of flexor digitorum longus attachment is found at
the posteromedial border of the tibia, which is the most common location of
medial tibial stress syndrome (MTSS). Therefore, plantar flexion strength of the
lesser toes could be related to MTSS; however, the relationship between MTSS and
muscle strength of the hallux and lesser toes is not yet evaluated due to the
lack of quantitative methods. This study investigated the muscle strength
characteristics in runners with a history of MTSS by using a newly developed
device to measure the muscle strength of the hallux, lesser toes, and ankle.
METHODS: This study comprised 27 collegiate male runner participants (20.0 +/-
1.6 years, 172.1 +/- 5.1 cm, 57.5 +/- 4.0 kg). Maximal voluntary isometric
contraction (MVIC) torque of the plantar flexion, dorsiflexion, inversion, and
eversion of the ankle were measured by using an electric dynamometer. MVIC torque
of the 1st metatarsophalangeal joint (MTPJ) and 2nd-5th MTPJ were measured by
using a custom-made torque-measuring device. MVIC torques were compared between
runners with and without a history of MTSS. RESULTS: MVIC torque of the 1st MTPJ
plantar flexion was significantly higher in runners with a history of MTSS than
in those without it. In contrast, there were no significant differences in the
MVIC torque values of the 2nd-5th MTPJ plantar flexion and each MVIC torque of
the ankle between runners with and without a history of MTSS. CONCLUSION: A
history of MTSS increased the isometric FHL strength.
PMID- 28413453
TI - Amelioration of intestinal and systemic sequelae of murine Campylobacter jejuni
infection by probiotic VSL#3 treatment.
AB - BACKGROUND: The incidence of human Campylobacter jejuni infections is
progressively increasing worldwide. Probiotic compounds might open up valuable
tools to decrease pathogen burden and subsequent pro-inflammatory immune
responses, but in vivo data are scarce. METHODS AND RESULTS: Secondary abiotic
mice generated by broad-spectrum antibiotic treatment were perorally challenged
with the commercial probiotic compound VSL#3 consisting of Streptococcus
thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium
infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus
paracasei, and Lactobacillus delbrueckii ssp. bulgaricus) either 5 days before
(i.e. prophylactic regimen) or after (i.e. therapeutic regimen) peroral C. jejuni
strain 81-176 infection, and analyzed 3 weeks following the initial bacterial re
association. Upon challenge, mice were colonized with the probiotic bacteria
and/or C. jejuni at comparable intestinal loads, but co-colonization did not
result in reduction of the pathogen burden. Remarkably, prophylactic as well as
therapeutic VSL#3 treatment of C. jejuni infected mice ameliorated intestinal
apoptosis and pro-inflammatory immune responses as indicated by lower numbers of
innate and adaptive immune cell populations in the murine colon upon probiotic
prophylaxis or treatment and reduced colonic concentrations of pro-inflammatory
mediators including IL-6 and MCP-1. Importantly, concentrations of anti
inflammatory mediators such as IL-10 were significantly elevated in the colon of
probiotics treated mice as compared to untreated controls. Strikingly,
prophylactic VSL#3 treatment attenuated C. jejuni induced systemic pro
inflammatory responses as indicated by less TNF and IL-12p70 secretion in the
spleen of VSL#3 pre-treated as compared to non-treated mice. CONCLUSION:
Administration of probiotic formulations such as VSL#3 might open up valuable
strategies for prophylaxis and/or treatment of C. jejuni induced intestinal and
systemic sequelae in vivo by the suppression of pro-inflammatory and induction of
anti-inflammatory responses.
PMID- 28413455
TI - Letter to editor: The waist circumference-adjusted associations between
hyperuricemia and other lifestyle-related diseases: methodological issues in
cross-sectional study.
PMID- 28413454
TI - Helicobacter pylori vacA s1m1 genotype but not cagA or babA2 increase the risk of
ulcer and gastric cancer in patients from Southern Mexico.
AB - BACKGROUND: The vacA, cagA and babA2 genotypes of Helicobacter pylori are
associated with gastric pathology. The objectives were to determine the frequency
of infection and distribution of the vacA, cagA and babA2 genotypes of H. pylori
in patients with gastric ulcer, chronic gastritis and gastric cancer, and to
evaluate the association of virulent genotypes with diagnosis. METHODS: We
studied 921 patients with symptoms of dyspepsia or with presumptive diagnosis of
gastric cancer. The DNA of H. pylori and the vacA, cagA and babA2 genes was
detected by PCR in total DNA from gastric biopsies. The association of H. pylori
and of its cagA, vacA and babA2 genotypes with diagnosis was determined by
calculating the odds ratio (OR). RESULTS: Chronic gastritis was confirmed in 767
patients, gastric ulcer in 115 and cancer in 39. The prevalence of H. pylori was
47.8, 49.6 and 61.5% in those groups, respectively. H. pylori was more frequent
in the surrounding tissue (69.2%) than in the tumor (53.8%). The vacA s1m1
genotype predominated in the three groups (45.2, 61.4 and 83.3%, respectively).
H. pylori was associated with cancer (ORadjusted = 2.08; 95% CI 1.05-4.13; p =
0.035) but not with ulcer (ORadjusted = 1.07; 95% CI 0.71-1.61; p = 0.728). The
s1m1 genotype was associated with ulcer and cancer (ORadjusted = 2.02; 95% CI
1.12-3.62; p = 0.019 and ORadjusted = 6.58; 95% CI 2.15-20.08; p = 0.001,
respectively). babA2 was associated with gastric cancer, and cagA was not
associated with the diagnosis. CONCLUSIONS: In population from Southern Mexico,
H. pylori and the s1m1 genotype were associated with gastric cancer and the
s1m1/cagA+/babA2+ strains predominated in tumor and adjacent tissue.
PMID- 28413456
TI - Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel
syndrome.
AB - Irritable bowel syndrome (IBS) is a functional bowel disease with a complicated
etiopathogenesis, often characterized by gastrointestinal motility disorder and
high visceral sensitivity. IBS is a comprehensive multi-systemic disorder, with
the interaction of multiple factors, such as mental stress, intestinal function
and flora, heredity, resulting in the disease. The existence of a common
mechanism underlying the aforementioned factors is currently unknown. The lack of
therapies that comprehensively address the disease symptoms, including abdominal
pain and diarrhea, is a limitation of current IBS management. The current review
has explored the role of the SCF/c-Kit receptor/ligand system in IBS. The SCF/c
Kit system constitutes a classical ligand/receptor tyrosine kinase signaling
system that mediates inflammation and smooth muscle contraction. Additionally, it
provides trophic support to neural crest-derived cell types, including the
enteric nervous system and mast cells. The regulation of SCF/c-Kit on the
interstitial cells of Cajal (ICC) suggest that it may play a key role in the
aberrant intestinal dynamics and high visceral sensitivity observed in IBS. The
role of the SCF/c-Kit system in intestinal motility, inflammation and nerve
growth has been reported. From the available biomedical evidence on the
pathogenesis of IBS, it has been concluded that the SCF-c-Kit system is a
potential therapeutic target for rational drug design in the treatment of IBS.
PMID- 28413457
TI - Persicarin isolated from Oenanthe javanica protects against diabetes-induced
oxidative stress and inflammation in the liver of streptozotocin-induced type 1
diabetic mice.
AB - Persicarin is one of the major components of the Oenanthe javanica (water
dropwort). The present study was aimed to evaluate the role of persicarin in the
hepatic tissue of streptozotocin-induced type 1 diabetic mice. Diabetes was
induced by single intra-peritoneal injection of streptozotocin (120 mg/kg body
weight) and then oral administration of persicarin at a dose 2.5 and 5 mg/kg body
weight for 10 days. Serum and hepatic glucose levels were increased in diabetic
control mice, while persicarin treatment groups were markedly reduced. Also, the
increased levels of ALT and AST in serum were improved by persicarin. In our
results revealed that persicarin suppressed increased oxidative stress parameter
(reactive oxygen species, peroxinitrite, and thiobarbituric acid-reactive
substance), nicotinamide adenine dinucleotide phosphate oxidase subunit (Nox-4
and P47phox) and inflammatory related makers (NF-kappaB, AP-1, TGF-beta, COX-2,
and iNOS). These results suggest that persicarin protects against liver damage by
attenuating oxidative stress and inflammatory response under hyperglycemic
conditions. Thus, persicarin could perform as a potential therapeutic agent for
the treatment of diabetic mellitus.
PMID- 28413458
TI - miR-9 functions as a tumor inhibitor of cell proliferation in epithelial ovarian
cancer through targeting the SDF-1/CXCR4 pathway.
AB - The current study aimed to investigate the potential role of miR-9 in the
inhibition of ovarian cancer progression through the stromal cell-derived factor
1 (SDF-1)/ C-X-C chemokine receptor type 4 (CXCR4) pathway and to provide a
theoretical basis for the diagnosis and treatment of ovarian cancer. Human
ovarian cancer OVCAR-3 cells were transfected with miR-9 short hairpin RNA
(shRNA). The effect of miR-9 on the mRNA expression levels of CXCR4 were analyzed
using reverse transcription-quantitative polymerase chain reaction. The effects
of miR-9 on OVCAR-3 cell proliferation, invasion and apoptotic ability were
detected using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide
assay, Matrigel method, and Annexin V-fluorescein isothiocyanate flow cytometry,
respectively. In addition, expression levels of SDF-1/CXCR4 pathway associated
proteins were determined by western blot analysis. mRNA expression levels of
CXCR4 in OVCAR-3 cells transfected with miR-9 shRNA was significantly
downregulated compared with the blank and control groups (P<0.05). Furthermore,
compared with the two control groups, the current results revealed that miR-9
inhibited cell proliferation, suppressed invasive ability and induced cell
apoptosis in OVCAR-3 cells (P<0.05). Finally, it was observed that miR-9
functioned as a tumor inhibitor through the SDF-1/CXCR4 pathway by suppressing
the expression levels of extracellular signal-regulated kinase 1 (ERK1), ERK2 and
matrix metalloproteinase-9 proteins. The present study suggested that miR-9 may
function as a promising tumor inhibitor for ovarian cancer through targeting the
SDF-1/CXCR4 pathway.
PMID- 28413459
TI - Expression levels of TGF-beta1 and CTGF are associated with the severity of
Duchenne muscular dystrophy.
AB - The present study aimed to analyze the association of transforming growth factor
beta1 (TGF-beta1) and connective tissue growth factor (CTGF) expression levels in
skeletal muscle with the clinical manifestation of Duchenne muscular dystrophy
(DMD). A total of 18 cases of DMD, which were confirmed by routine pathological
diagnosis were recruited into the present study, along with 8 subjects who
suffered from acute trauma but did not present any neuromuscular diseases and
were enrolled as the healthy controls. Immunohistochemical staining was used to
detect the expression levels of CTGF and TGF-beta1 in muscle biopsy specimens.
Furthermore, Spearman rank correlation analysis was conducted among the
expression levels of CTGF and TGF-beta1, age, clinical severity and pathological
severity in DMD patients. The immunohistochemical staining results revealed that
the expression levels of CTGF and TGF-beta1 were significantly increased in the
DMD group compared with those in the control group (P<0.05). These levels were
not found to be significantly correlated with the onset age (P>0.05), but there
was a significant correlation with the degree of pathology and clinical severity
(P<0.05). In conclusion, an upregulated expression of CTGF and TGF-beta1 was
revealed in the skeletal muscle of DMD patients, which were in positive
correlation with the degree of pathology and clinical severity. These two factors
may be involved in the pathophysiology of fibrosis in DMD.
PMID- 28413460
TI - Early application of low-dose glucocorticoid improves acute respiratory distress
syndrome: A meta-analysis of randomized controlled trials.
AB - Previous clinical trials have investigated the effect of glucocorticoid therapy
in acute respiratory distress syndrome (ARDS), with controversial results,
particularly with regard to the early administration of low dose glucocorticoid.
The present meta-analysis aimed to assess whether the application of
glucocorticoid was able to reduce mortality in patients with ARDS. A literature
search was performed using online databases, including MEDLINE, Embase, Cochrane
and CNKI regardless of whether the studies were published in English or Chinese.
Following assessment via inclusion and exclusion criteria, two reviewers screened
controlled randomized trials which investigated glucocorticoid therapy in ARDS
patients and independently extracted data. The quality of all of the included
trials was evaluated based on blinding, randomization and other methods. A total
of 14 studies with 1,441 patients met the inclusion criteria. The results of the
meta-analysis demonstrated that glucocorticoid significantly reduced the overall
mortality of patients with ARDS [relative ratio (RR), 0.68; 95% confidence
interval (CI), 0.50-0.91; P<0.05], particularly with a low-dose of glucocorticoid
(RR, 0.57; 95% CI, 0.39-0.84; P<0.05) at the early phase of ARDS (RR, 0.37; 95%
CI, 0.16-0.86; P<0.05), and a longer duration of steroids (RR, 0.44; 95% CI, 0.30
0.64; P<0.05). Administration of steroids also significantly increased the number
of days that patients remained alive and were off mechanical ventilation (RR,
3.08; 95% CI, 1.49-4.68; P<0.05) without significantly increasing the novel
infection rate (RR, 1.00; 95% CI, 0.44-2.25; P<0.05). Due to inconsistencies and
other limitations, the quality of the studies used for the meta-analysis of the
effect of glucocorticoid on mortality was low. In conclusion, early use of low
dose glucocorticoid may effectively reduce mortality in patients with ARDS.
However, this conclusion may be affected by the limited quality of the studies
included in the present meta-analysis.
PMID- 28413461
TI - Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose
deprivation and reoxygenation in human brain microvascular endothelial cells.
AB - Cerebral ischemia/reperfusion (I/R) injury leads to brain vascular dysfunction,
which is characterized by endothelial cell injury or death. Long noncoding (lnc)
RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reportedly
associated with endothelial cell functions and dysfunctions. In the present
study, the role of MALAT1 in I/R-induced cerebral vascular endothelial cell
apoptosis was explored using oxygen-glucose deprivation and reoxygenation (OGD-R)
as an in vitro I/R injury model. Primary human brain microvascular endothelial
cells were cultured under OGD-R, and the expression levels of MALAT1 and cell
apoptosis were measured at 6, 9, 12, 24 and 36 h post-reoxygenation. The
expression levels of MALAT1 and the apoptotic rate of cells exposed to OGD-R
exhibited contrasting trends following reoxygenation. Following OGD-R, lentiviral
overexpression of MALAT1 increased phosphatidylinositol 3-kinase (PI3K)
activities and the activation of Akt phosphorylation, and decreased cell
apoptosis and caspase 3 activities, which were successfully abolished by
treatment with a PI3K inhibitor, Wortmannin. Conversely, lentiviral knockdown of
MALAT1 decreased PI3K activities and the activation of Akt phosphorylation, and
increased cell apoptosis and caspase 3 activity. Overexpression and knockdown of
MALAT1 exhibited no significant effects on OGD-R-induced reactive oxygen species
(ROS) production. In conclusion, to the best of our knowledge, the present study
was the first to suggest that lncRNA MALAT1 may protect human brain vascular
endothelial cells from OGD-R-induced apoptosis via a PI3K-dependent mechanism.
These findings suggest that MALAT1 may be a potential novel therapeutic target
for cerebral I/R injury.
PMID- 28413462
TI - Identification of miRNA biomarkers of pneumonia using RNA-sequencing and
bioinformatics analysis.
AB - Pneumonia is a lower respiratory tract infection that causes dramatic mortality
worldwide. The present study aimed to investigate the pathogenesis of pneumonia
and identify microRNA (miRNA) biomarkers as candidates for targeted therapy. RNA
from the peripheral blood plasma of participants with pneumonia (severe, n=9; non
severe, n=9) and controls (n=9) was isolated and paired-end sequencing was
performed on an Illumina HiSeq4000 system. Following the processing of raw reads,
the sequences were aligned against the Genome Reference Consortium human genome
assembly 38 reference genome using Bowtie2 software. Reads per kilobase of
transcript per million mapped read values were obtained and the limma software
package was used to identify differentially expressed miRNAs (DE-miRs). Then, DE
miR targets were predicted and subjected to enrichment analysis. In addition, a
protein-protein interaction (PPI) network of the predicted targets was
constructed. This analysis identified 11 key DE-miRs in pneumonia samples,
including 6 upregulated miRNAs (including hsa-miR-34a and hsa-miR-455) and 5
downregulated miRNAs (including hsa-let-7f-1). All DE-miRs kept their
upregulation/downregulation pattern in the control, non-severe pneumonia and
severe pneumonia samples. Predicted target genes of DE-miRs in the subjects with
non-severe pneumonia vs. the control and the subjects with severe pneumonia vs.
the non-severe pneumonia group were markedly enriched in the adherens junction
and Wnt signaling pathways. KALRN, Ras homolog family member A (RHOA), beta
catenin (CTNNB1), RNA polymerase II subunit K (POLR2K) and amyloid precursor
protein (APP) were determined to encode crucial proteins in the PPI network
constructed. KALRN was predicted to be a target of hsa-mir-200b, while RHOA,
CTNNB1, POLR2K and APP were predicted targets of hsa-let-7f-1. The results of the
present study demonstrated that hsa-let-7f-1 may serve a role in the development
of cancer and the Notch signaling pathway. Conversely, hsa-miR-455 may be an
inhibitor of pneumonia pathogenesis. Furthermore, hsa-miR-200b might promote
pneumonia via targeting KALRN.
PMID- 28413463
TI - Diagnostic value of neutrophil gelatinase-associated lipocalin for renal injury
in asphyxiated preterm infants.
AB - The aim of the present study was to analyze the diagnostic value of neutrophil
gelatinase-associated lipocalin (NGAL) in renal injury in asphyxiated preterm
infants. In total, 48 cases of asphyxiated preterm infants, 45 cases of premature
infants and 45 cases of normal newborn infants were included in the study. Using
ELISA we evaluated the level of urine NGAL, kidney injury molecule-1 (KIM-1),
cystatin C (Cys-C) and serum creatinine (Scr). We also calculated the estimated
glomerular filtration rate (eGFR). Our results showed that NGAL, KIM-1 and Cys-C
levels in the group of asphyxiant renal injury within 24 and 48 h were markedly
higher than the other two groups (P<0.05), while changes in Scr and eGFR within
24 h were not significant (P>0.05). Scr level in renal injury group within 48 h
was markedly elevated while the eGFR level was visibly reduced (P<0.05).
According to analysis of receiver operating characteristic curve, area under
curve for NGAL in the group of asphyxiant renal injury within 24 and 48 h was
significantly higher than KIM-1 and Cys-C. Susceptibility and specificity were
improved. In conclusion, diagnosis of renal injury in asphyxia neonates using
NGAL was more efficient compared to other methods.
PMID- 28413465
TI - Protective effects of baicalin on rabbit articular chondrocytes in vitro.
AB - Drug therapy is one of the typical treatments for post-injury inflammation of
cartilage. Traditional Chinese herbs have potential as treatments, as their long
history of clinical application has demonstrated they are effective and induce
minimal side effects. Baicalin is a traditional Chinese medicine that has been
used to treat inflammation, fever, ulcers and cancer for hundreds of years.
Previous studies have demonstrated that baicalin may decrease levels of
interleukin-1beta and suppress the expression of type-I collagen, thus
attenuating cartilage degeneration. In the present study, the effect of baicalin
on chondrocytes was assessed by examining the morphology, proliferation,
extracellular matrix (ECM) synthesis and cartilage-specific gene expression of
chondrocytes. The results indicated that baicalin may promote the proliferation
of articular chondrocytes, secretion of cartilage ECM and collagen type II,
aggrecan and SRY box (Sox) 9 gene upregulation. The expression of collagen I, a
marker of chondrocyte dedifferentiation, was downregulated by baicalin;
therefore, baicalin may maintain the phenotype of chondrocytes. Within the
recommended concentrations of baicalin ranging from 0.625-6.25 umol/l cell
proliferation was increased and a 1.25 umol/l dose of baicalin exerted the most
positive effect on articular chondrocytes. The results of the present study may
therefore indicate that baicalin may be used as a novel agent promoting the
repair of articular cartilage damage.
PMID- 28413466
TI - Analysis of missed diagnosis of orbital foreign bodies.
AB - A clinical analysis of diagnosis was performed as well as the management of
orbital foreign bodies, to investigate the methods to avoid missed diagnosis. A
total of 15 cases of an orbital foreign body was reviewed, and for these cases,
the clinical manifestation, imaging data and operative situation were studied.
Among the patients, 4 cases turned out to have wooden, 3 metallic, 2 glass, 2
bones, and 4 other foreign bodies. Twelve cases had received debridement and
suture before our management, and 1 foreign body was treated more than once. In
conclusion, detailed traumatic history and imaging examination are necessary for
the diagnosis of orbital foreign bodies, while prompt diagnosis, accurate
location and professional surgical skills are important for the treatment.
PMID- 28413464
TI - Anti-climacterium effects of pomegranate concentrated solutions in ovariectomized
ddY mice.
AB - In the present study, the complex anti-climacterium potential of standardized
pomegranate concentrated solution (PCS) was investigated using bilateral
ovariectomy (OVX) female ddY mice. Changes in body weight and gain during
experimental periods, food consumption, serum estradiol levels, total body and
abdominal fat densities, abdominal fat pads, and uterus weights were observed,
along with the histopathology of abdominal fat pads and uterus for anti-obesity
and estrogenic effects. In addition, liver weights, serum aspartate
aminotransferase (AST), alanine aminotransferase (ALT) levels, and
histopathological inspections were performed to explore the hepato-protective
effects. Serum total cholesterol (TC), low density lipoprotein (LDL), high
density lipoprotein, and triglyceride (TG) levels were monitored for
hypolipidemic effects with total body and femur mean bone mineral density (BMD),
right femur wet, dry and ash weights, strength, serum osteocalcin, bone-specific
alkaline phosphatase (bALP) contents, and histological and histomorphometrical
analyses for anti-osteoporosis activity. As a result of OVX, notable increases in
body weight and gains, food consumption, abdominal fat mass densities, weights of
abdominal fat pads deposited in the abdominal cavity, and serum AST, ALT, TC,
LDL, TG, and osteocalcin levels were observed, along with decreases in the
uterus, liver, and femur weights, mean total body and femur BMD, femur strength,
serum bALP, and estradiol levels. In addition, marked hypertrophic alterations in
adipocytes located in the deposited abdominal fat pads, liver steatosis, uterine
disused atrophic changes, and decreases in bone mass and structures of the femur
were also observed in OVX control mice with significant increases in bone
resorption markers based on histopathological and histomorphometrical analysis.
However, these estrogen-deficient climacterium symptoms were significantly
(P<0.05 or P<0.01) inhibited after 84 days of continuous treatment with estradiol
and PCS (1, 2 and 4 ml/kg), respectively. The present results suggested that PCS
was able to effectively inhibit or refine the climacterium symptoms, including
obesity, hyperlipidemia, hepatic steatosis, and osteoporosis, induced by OVX in
ddY mice.
PMID- 28413467
TI - Calcitonin gene-related peptide protects type II alveolar epithelial cells from
hyperoxia-induced DNA damage and cell death.
AB - Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive
oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related
peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome
activation. However, the role of CGRP in DNA damage during hyperoxia is unclear.
Therefore, the aim of the present study was to investigate the effects of CGRP on
DNA damage and the cell death of alveolar epithelial type II cells (AEC II)
exposed to 60% oxygen. AEC II were isolated from 19-20 gestational day fetal rat
lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the
specific CGRP receptor antagonist CGRP8-37. The cells were evaluated using
immunofluorescence to examine surfactant protein-C and ROS levels were measured
by probing with 2',7'-dichlorofluorescin diacetate. The apoptosis rate and cell
cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by
western blotting analysis of activated caspase 3. The DNA damage was confirmed
with immunofluorescence of H2AX via high-content analysis. The ROS levels,
apoptotic cell number and the expression of gammaH2AX were markedly increased in
the hyperoxia group compared with those in the air group. Concordantly, ROS
levels, apoptotic cell number and the expression of gammaH2AX were significantly
lower with a significant arrest of S and G2/M phases in the CGRP/O2 group than in
the hyperoxia or CGRP8-37/O2 groups. CGRP was concluded to protect lung
epithelium cells against hyperoxic insult, and upregulation of CGRP may be a
possible novel therapeutic target to treat hyperoxic lung injury.
PMID- 28413468
TI - Antitumor effect of sunitinib in human prostate cancer cells functions via
autophagy.
AB - The aim of the present study was to explore sunitinib-induced autophagic effects
and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP
human prostate cancer cell lines. Cells were exposed to escalating doses of
sunitinib treatment and subsequent cell viability and cell cycle analyses were
performed to evaluate the inhibitory effect of sunitinib in vitro.
Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3
(LC3) puncta was employed to assess autophagy levels after sunitinib treatment.
Western blot analysis was performed to evaluate variations in the levels of LC3,
sequestosome-1, extracellular signal regulated kinase 1/2 (ERK1/2), mammalian
target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K) and cleaved
caspase-3 proteins. The present study revealed that sunitinib treatment inhibited
cell growth and triggered autophagy in a dose-dependent manner in both cell
lines. In addition, sunitinib activated ERK1/2 and inhibited mTOR/p70S6K
signaling. Sunitinib-induced autophagy was notably reversed by ERK1/2 kinase
inhibitor, U0126. Furthermore, inhibition of sunitinib-induced autophagy by 3
methyladenine enhanced apoptosis and exhibited improved cell viability, which
indicated that sunitinib induces not only apoptosis but also autophagic cell
death in prostate cancer cell lines. These results may lead to an improved
understanding of the mechanism of sunitinib's cytotoxic action and may provide
evidence that combined sunitinib autophagy-regulating treatment may be of benefit
to anti-prostate cancer therapy.
PMID- 28413469
TI - Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with
autoimmune thyroiditis.
AB - The aim of the present study was to determine the repairing effects of
intercellular adhesion molecule (ICAM)-1-expressing mesenchymal stem cells (MSCs)
in mice with autoimmune thyroiditis. Following induction of an experimental
autoimmune thyroiditis (EAT) model, mice were randomly divided into the following
groups (n=10 each): i) Normal control; and experimental groups that were subject
to EAT induction, including ii) EAT model; and iii) primary MSC; iv)
C3H10T1/2/MSC; v) C3H10T1/2-MIGR1/MSC; and vi) C3H10T1/2-MIGR1-ICAM-1/MSC, which
were all administered the relevant cells. MSCs were administered via the caudal
vein. A blood sample was harvested from the angular vein of each animal 28 days
post-treatment and ELISA was used to determine the serum total triiodothyronine,
total thyroxine (T4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase
(TPOAb), anti-thyroid microsomal (TMAb) and anti-thyroglobulin (TGAb) antibodies.
Hematoxylin and eosin staining was performed to evaluate injury of the thyroid
gland by determining the size of the follicle, inflammatory infiltration,
colloidal substance retention and epithelial injury. Reverse transcription
quantitative polymerase chain reaction was performed to determine the mRNA
expression of interleukin (IL)-4, IL-10, IL-17 and interferon (INF)-gamma.
Western blot analysis was performed to determine the expression of p38 mitogen
activated protein kinase (p38) and extracellular signal-regulated kinase (ERK).
To observe cellular migration in vivo, mice were divided into the following
groups, (n=10 each), which were subject to EAT induction: i) CM-DiI-labeled
primary MSC; ii) CM-DiI-labeled C3H10T1/2/MSC; iii) CM-DiI-labeled C3H10T1/2
MIGR1/MSC; and iv) CM-DiI-labeled C3H10T1/2-ICAM-1/MSC, which were all
administered the relevant cells via the caudal vein. C3H10T1/2-ICAM-1/MSCs were
able to ameliorate the expression of T4, TSH, TPOAb, TMAb and TGAb in vivo,
attenuate thyroid follicle injury and decrease the splenic index in mice. They
were also able to ameliorate the mRNA expression of IL-4, IL-10, IL-17 and INF
gamma, and the modulation of the P38 and ERK-signaling pathways in the mouse
spleen. Furthermore, ICAM-1 overexpression was able to modulate the nesting of
MSCs in the thyroid gland and lung. These findings suggest that C3H10T1/2-ICAM
1/MSC may affect the differentiation, proliferation and migration of immunocytes
through modulating the p38 and ERK signaling pathways, and that ICAM-1 may
modulate the immunoregulatory effects of MSCs by affecting the migration of MSCs
in vivo.
PMID- 28413470
TI - Identification of genes associated with the effect of inflammation on the
neurotransmission of vascular smooth muscle cell.
AB - Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in
vascular disorders, and inflammation has a crucial role in the development of
these diseases. To investigate the effect of inflammation on the
neurotransmission of VSMC, bioinformatic analysis was performed, following next
generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and
phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next
generation sequencing, and each assay was repeated three times. Differentially
expressed genes (DEGs) were obtained using the NOISeq package in R. Subsequently,
their potential functions were predicted by functional and pathway enrichment
analyses using the Database for Annotation, Visualization and Integrated
Discovery online tool. Interaction relationships of the proteins enriched in
pathways associated with neurological diseases, the proteins which had
interaction relationships with adrenoceptor alpha 1D (ADRA1D) or calcium voltage
gated channel subunit alpha1 S (CACNA1S), separately, were obtained from STRING,
and protein-protein interaction (PPI) networks were constructed using Cytoscape
software. A total of 2,038 DEGs, including 1,094 upregulated and 944
downregulated genes in the LPS treatment group were identified when compared with
the control group. Enrichment analyses showed that NADH:Ubiquinone Oxidoreductase
Core Subunit V2 (NDUFV2) was involved in several neurological diseases, including
oxidative phosphorylation, Alzheimer's disease, Parkinson's disease and
Huntington's disease. Furthermore, NDUFV2 (degree, 20) had a higher degree in the
PPI network for DEGs enriched in pathways associated with neurological diseases.
In the PPI network for ADRA1D, CACNA1S and the DEGs interacting with them,
prohibitin (PHB), oxytocin receptor (OXTR), collapsin response mediator protein 1
(CRMP1) and dihydropyrimidinase like 2 (DPYSL2) had interaction relationships
with both ADRA1D and CACNA1S. To conclude, the present study revealed that
NDUFV2, PHB, OXTR, CRMP1 and DPYSL2 may have key roles in the effect of
inflammation on neurotransmission of VSMC.
PMID- 28413471
TI - Influence of camel milk on the hepatitis C virus burden of infected patients.
AB - Hepatitis C virus (HCV) infection represents a world health problem and no
protective vaccine or effective drug currently exists. For economic reasons, many
patients use traditional medicines to control the infection. In Egypt, camel milk
is one of the traditional medicines widely consumed by patients infected with
HCV. The present study aimed to evaluate the efficacy of camel milk in the
treatment of patients infected with HCV. Whole camel milk from a local farm was
administered to patients for 4 months (250 ml/day/patient). Patient sera were
collected prior to and following camel milk drinking, and three markers were set
up for sera-evaluation. The three markers indicating the effect of camel milk on
HCV infection were: Liver function assays [alanine aminotransferase (ALT) and
aspartate aminotransferase (AST)]; a viral load assay; and anti-HCV antibodies
profile and isotyping against synthetic HCV epitopes. Camel milk demonstrated the
ability to improve general fatigue, health and liver function (ALT and AST
levels); ALT was reduced in ~88% of patients and AST was reduced in all patients
subsequent to drinking camel milk for four months. The majority of patients
responded positively to camel milk treatment; RNA viral load decreased in 13 out
of the 17 patients (76.47%) and one patient exhibited undetected viremia
following camel milk treatment. The anti-HCV antibodies profile and isotyping
were significantly decreased (P<0.05) in immunoglobulin (Ig)G1 following
treatment in 70-76% of patients. However, the treatment was ineffective in 23.53%
of patients who experienced no reduction in RNA viral load following treatment
with camel milk. In conclusion, whole camel milk treatment demonstrated efficacy
in vivo; the viral load in the majority of patient sera was reduced and the IgG
isotype profile was converted to Th1 immunity.
PMID- 28413472
TI - Anti-diabetic effect of Alpinia oxyphylla extract on 57BL/KsJ db-/db- mice.
AB - Diabetes mellitus is characterized by high blood glucose levels. Increased levels
of reactive oxygen species (ROS) may disrupt insulin signaling and result in
insulin resistance. The Alpinia oxyphylla extract (AOE) possesses powerful
antioxidant activity and may therefore inhibit the development of insulin
resistance. The objective of the present study was to determine the effects of
AOE on blood glucose, insulin and lipid levels in a type II diabetic nephropathy
animal model (C57BIKsj db-/db-). All experiments were performed on male C57BL/Ks
DB/DB and db-/db- mice that were left to acclimatize for 1 week prior to the
experimental period. AOE was administered to these mice at different dosages
(100, 300 and 500 mg/kg) for 8 weeks. The results demonstrated that AOE did not
affect mouse weight, while blood glucose concentrations were found to
significantly decrease in a dose-dependent manner (P<0.05). The effect of
administering 500 mg/kg AOE (AOE500) to db-/db- mice was tested further.
Treatment with AOE500 for 8 weeks led to improved glucose tolerance and reduced
plasma insulin concentrations (P<0.05), as well as a significant decrease in
triglyceride concentrations (P<0.05) and levels of total cholesterol (P<0.05) in
db-/db- mice. Furthermore, treatment with AOE500 decreased the concentration of
malondialdehyde, elevated the concentration of glutathione and increased the
activities of the antioxidant enzymes superoxide dismutase and peroxidase
(P<0.05) in the livers of db-/db- mice. Meanwhile, AOE-treated mice exhibited
significantly reduced urine albumin, creatinine and blood urea nitrogen excretion
(P<0.05). In parallel, the upregulated expression of phosphatase and tensin
homolog (PTEN) in the liver and kidneys of db-/db- mice was impaired following
AOE500 treatment. The results of the present study suggest that AOE regulates
blood glucose and lipid levels and improves renal function by mediating oxidative
stress and PTEN expression at the onset of type II diabetes mellitus.
PMID- 28413473
TI - MicroRNA-200c suppresses cell growth and metastasis by targeting Bmi-1 and E2F3
in renal cancer cells.
AB - The aim of the present study was to evaluate the functions of miR-200c in the
regulation of tumor growth and metastasis in renal cancer cells, and to
investigate the underlying mechanisms. In this study, miR-200c was up- and
downregulated in two renal cancer cell lines, namely ACHN and A498, and the
proliferation, colony formation, migration and invasion of the cells were
measured. The expression levels of various mRNAs and proteins were then analyzed
using reverse transcription-quantitative polymerase chain reaction and western
blotting, respectively. It was found that miR-200c suppressed proliferation,
migration and invasion of the renal cancer cells and, conversely, the inhibition
of endogenous miR-200c resulted in increased cell proliferation and metastasis.
Furthermore, a luciferase reporter assay revealed that miR-200c directly targeted
the 3' untranslated regions of the oncogenes B-cell-specific Moloney murine
leukemia virus insertion site 1 (Bmi-1) and E2F transcription factor 3 (E2F3)
mRNAs, reduced the expression of Bmi-1 and E2F3 and regulated the expression of
downstream genes, including E-cadherin, N-cadherin, vimentin, p14 and p16. These
results indicate a tumor suppressor role for miR-200c in renal cancer cells via
the direct targeting of Bmi-1 and E2F3.
PMID- 28413474
TI - Obesity contributes more to increasing ApoB/ApoA1 ratio than hyperandrogenism in
PCOS women aged 20-38 years in China.
AB - We investigated the association between the apolipoprotein B
(ApoB)/apolipoprotein A1 (ApoA1) ratio and insulin resistance (IR), metabolic
syndrome (MS) and its components in Chinese polycystic ovary syndrome (PCOS)
adults. We also examined whether hyperandrogenism is involved in obesity-related
metabolic abnormalities in a cohort of patients. A clinical cross-sectional study
consisting of 532 Chinese PCOS adults aged 20-38 years was designed. Each subject
underwent a physical examination and laboratory evaluation. We found that the
ApoB/ApoA1 ratio was significantly higher in patients with MS compared to those
without MS. This test provided 83.6% sensitivity and 67.6% specificity with a
threshold value of 0.60 in MS. The ApoB/ApoA1 ratio increased significantly as
the number of MS components increased. After adjusting for age, the patients with
MS or IR were more likely to be in the high ApoB/ApoA1 group, and the ApoB/ApoA1
ratio was associated significantly with each of the MS components, high free
testosterone (FT), and high free androgen index (FAI). After adjusting for age
and body mass index (BMI), the association persisted for all factors excluding
high blood pressure (BP), high fasting plasma glucose (FPG), high FT, and high
FAI. Therefore, the ApoB/ApoA1 ratio was strongly associated with IR, MS and its
components, high FT, and high FAI. A high ApoB/ApoA1 ratio appears to be a good
predictive marker of MS in Chinese PCOS adults. Obesity, especially central
obesity, contributes more to increasing ApoB/ApoA1 ratio than increased BP, FPG,
FT and FAI in this cohort of PCOS patients.
PMID- 28413475
TI - Evaluation of the role of human beta-defensin 3 in modulation of immunity and
inflammatory response after knee replacement.
AB - The present study investigated the value of human beta-defensin 3 (HBD-3) in
adjusting the immunity and inflammatory response of T lymphocytes in the body
after knee replacement. Sixty-four cases of knee replacement patients were
successively selected and randomly divided into the control group and the
observation group each with 32 cases. Once a day, for 7 days, patients in the
control group were injected with placebo saline solution in the articular cavity.
Levels of Th1 and/Th2, interleukin (IL)-2 and IL-10, tumor necrosis factor (TNF)
alpha, toll-like receptor (TLR)-4, and alkaline phosphatase (ALP) were compared
one month later, and implant infection rates were compared within 1-year follow
up. Compared with patients in the control group, the levels of Th1 and Th1/Th2 in
the observation group significantly increased, yet their Th2 decreased. The
levels of IL-2 and TNF-alpha were also observed to be significantly elevated, yet
IL-10 decreased. Furthermore, their TLR-4 and ALP levels were significantly
higher. Three cases of implant-related infection occurred in the control group
and 1 case in the observation group. In conclusion, HBD-3 could adjust the
immunity and inflammatory response of cells in the body after knee replacement,
possibly playing an important role in implant-related infection.
PMID- 28413476
TI - The mechanism of human beta-defensin 3 in MRSA-induced infection of implant drug
resistant bacteria biofilm in the mouse tibial bone marrow.
AB - The mechanism of human beta-defensin 3 (HBD-3) in methicillin-resistant
Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria
biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague
Dawley rats with average weight of 230 g were selected to construct the infection
model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left
tibial bone marrow. The drugs were intraperitoneally injected after 24 h
medullary cavity infection, and the experimental groups included the model group,
HBD-3 group, and vancomycin group (20 rats in each group). The model group was
injected with 10 ml saline, HBD-3 group was injected with 10 ml of 8 ug/ml (1
MIC) and vancomycin group was injected with 10 ml of 0.5 ug/ml (1 MIC), five
animals in each group were sacrificed on the 1, 7, 14 and 21 days, respectively.
Observation was carried out on whether there was swelling and purulent secretion
on the local wound; 1 ml venous sinus blood of eye socket was collected for blood
routine examination and blood culture, and the laser scanning confocal microscopy
was used to observe the morphology of the biofilm on the implant surface and the
number of viable bacteria. Immunohistochemical staining was adopted to test the
expression of nuclear factor-kappaB (NF-kappaB) and toll-like receptor 4 (TLR-4),
and ELISA method was used to test interleukin-10 (IL-10), tumor necrosis factor
alpha (TNF-alpha), IL-1alpha and interferon-gamma (INF-gamma)-inducible protein
10 (IP-10) expression levels. There was no death due to infection in the HBD-3
group or vancomycin group, 1 case with significant wound swelling was found,
respectively, in each group, but there was no purulent secretion. The percentage
of the total white blood cells and neutrophil granulocytes as well as the biofilm
morphology and the number of viable bacteria in the model group was gradually
increased with time, while those in the HBD-3 group and vancomycin group were
decreased with time. The comparative difference among groups was statistically
significant (P<0.05); those in the HBD-3 group and vancomycin group at each time
point was decreased significantly compared with the model group, and the
difference among groups was statistically significant (P<0.05), but in terms of
the comparison between the HBD-3 group and vancomycin group, the difference was
not significantly different (P>0.05). The NF-kappaB and TLR-4 expressions in the
model group and vancomycin group were not significantly changed at each time
point, those in the HBD-3 group began to increase on the 1st day, and reached the
peak on the 7th day and began to decline on the 14th day, and the comparative
difference at each time-point was statistically significant (P<0.05); those in
the HBD-3 group were significantly higher than the model group and vancomycin
group at each time-point and the difference was statistically significant
(P<0.05). The IL-10, TNF-alpha, IL-1alpha, and IP-10 expressions in the model
group at each time were significantly higher than the other two groups and the
difference was statistically significant (P<0.05); in terms of the comparison
between the HBD-3 group and vancomycin group, the difference was not
statistically significant (P>0.05). In conclusion, beta-defensin 3 can inhibit
the bacterial growth by regulating inflammation and immune responses in the MRSA
induced implant drug-resistant bacteria biofilm infection in the mouse tibial
bone marrow.
PMID- 28413477
TI - Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral
ischemia-reperfusion injury in vivo and in vitro.
AB - Isoquercetin has exhibited a wide range of therapeutic properties, including
antioxidant, anti-inflammatory and anti-allergic activities. The aim of the
present study was to investigate the effect of isoquercetin on rats with 2 h
middle cerebral artery occlusion (MCAO) and evaluate the neuroprotective effect
of isoquercetin on a primary culture of rat hippocampal neuronal cells subjected
to oxygen-glucose deprivation followed by reoxygenation (OGD/R). In vivo, the
rats treated with isoquercetin exhibited a lower degree of neurological
dysfunction and smaller infarct volume than the vehicle-treated rats. In vitro,
it was found that isoquercetin prevented the OGD/R-induced increase in apoptosis,
lactate dehydrogenase release and reduction in cell viability. Additionally,
isoquercetin induced the upregulation of nuclear factor erythroid 2-related
factor 2 gene and protein expression, and increased extracellular signal
regulated kinase 1 and 2 (ERK1/2) phosphorylation. This indicates that the ERK1/2
pathway may contribute to the neuroprotective effect of isoquercetin against
OGD/R-induced oxidative damage in rat hippocampal neurons. These findings suggest
the potential importance of isoquercetin in the treatment of ischemia/reperfusion
related brain injury and associated diseases.
PMID- 28413479
TI - Inhalative and intravenous stimulation of soluble guanylate cyclase reduces
pulmonary vascular resistance and increases cardiac output in experimental septic
shock.
AB - The effects of inhaled and intravenous application of a guanylate cyclase
stimulator (BAY 41-8543) on pulmonary vascular resistance (PVR) and cardiac
output (CO) were investigated in an experimental model of septic shock. Following
induction of septic shock, anaesthetized pigs (n=31) were randomly place into two
groups receiving different interventions. Animals in the first group received
intravenous BAY 41-8543 (0.6 mg), inhalative BAY 41-8543 (6 mg) or a placebo. In
the second group, the dosage of BAY 41-8543 was increased two-fold or combined
with inhalation of nitric oxide (iNO). Intravenous and inhaled administration of
BAY 41-8543 resulted in a significantly (P<0.05) reduced PVR and increased CO
compared with the placebo. Increasing the dosage of BAY 41-8543 or combining it
with iNO did not further decrease PVR. The results of the present study indicate
that BAY 41-8543 effectively reduces PVR and increases CO in septic shock,
through inhaled or intravenous routes of administration.
PMID- 28413478
TI - Icariin improves osteoporosis, inhibits the expression of PPARgamma, C/EBPalpha,
FABP4 mRNA, N1ICD and jagged1 proteins, and increases Notch2 mRNA in
ovariectomized rats.
AB - Icariin (ICA) is a pharmacologically active flavonoid glycoside that shows
promise in the treatment and prevention of osteoporosis (OP). However, the
mechanisms underlying the anti-osteoporotic effects of ICA remain largely
unclear. The present study used quantitative polymerase chain reaction, western
blot and immunohistochemical analysis to examine the effects of ICA on several
key targets in the Notch signaling pathway in bone tissue in ovariectomized rats.
It was observed that ICA has a pronounced beneficial effect on OP rats and
inhibits the expression of peroxisome proliferator-activated receptor gamma
(PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha) and fatty acid
binding protein 4 (FABP4) mRNA. In addition, it was identified that ICA
downregulates the expression of notch1 intracellular domain (N1ICD) and Jagged1
proteins in bone tissue, and suppresses the effect of N1ICD on Notch2 mRNA
expression. It is proposed that ICA inhibits the differentiation of mesenchymal
stem cells into adipocytes by inhibiting the expression of PPARgamma, C/EBPalpha
and FABP4 mRNA via the Notch signaling pathway. In addition, it is proposed that
ICA inhibits the expression of Notch2 mRNA by suppressing the effect of N1ICD. In
conclusion, the results provide further mechanistic evidence for the clinical
efficacy of ICA in the treatment of OP.
PMID- 28413480
TI - Analysis of the mechanism by which nerve growth factor promotes callus formation
in mice with tibial fracture.
AB - The aim of the present study was to analyze the mechanism by which nerve growth
factor (NGF) promotes callus formation in mice with tibial fracture. NGF
transgenic homozygotic mice and NGF wild homozygotic mice were selected to
construct non-stabilized fracture model of tibia. The mice were sacrificed on
days 7, 14 and 21, respectively, and each group had a sample with 8 mice at each
point in time. X-ray radiography and safranin fast green were used to observe
fracture healing and in situ hybridization was used to examine the NGF mRNA
expression of tibia at each phase of fracture healing. Tartrate-resistant acid
phosphatase (TRAP) staining of callus tissue and the expression level of TRAP
mRNA were combined to observe osteoclast formation. COL2A1, a chondrocyte
differentiation-related gene in callus, and the mRNA level of SOX9 were combined
to observe chondrocyte differentiation. It was found that under X-ray
radiography, the fracture of NGF transgenic homozygotic mice healed in advance
(P<0.05). Cartilage and bone tissue were identified by safranin and fast green
staining. The residual cartilage on the callus tissue of NGF transgenic
homozygotic mice had decreased significantly (P<0.05). The NGF mRNA expression
level in each phase of callus formation of NGF transgenic homozygotic mice was
significantly higher than that of the wild group (P<0.05). The number of positive
cells in NGF-TRAP staining at each time point after fracture and the NGF mRNA
expression level was markedly higher than that of the wild group, and the
expression levels of COL2A1 and SOX9 mRNA were distinctively higher than that of
the wild group. In conclusion, NGF potentially improves the healing of tibial
fracture by osteoclast formation. Additionally, an increase in the number of
osteoblasts in the NGF transgenic homozygotic mice compared with the wild-type
mice may be achieved by cartilage differentiation due to NGF increasing the
COL2A1 and SOX9 mRNA expression levels.
PMID- 28413481
TI - Oxymatrine on Hsp90a expression and apoptosis in a model of lung ischemia
reperfusion injury.
AB - The protective effects of oxymatrine (OMT) on apoptosis and heat shock protein
90a (Hsp90a) expression in a rabbit model of lung ischemia-reperfusion injury
(LIRI) were investigated. The model of LIRI was established in rabbits and they
were randomly divided into two groups: The control group (group C, n=10), and
experimental group (further divided into groups E1, n=10; and group E2, n=10), to
measure the levels of malondialdehyde (MDA) and superoxide dismutase (SOD)
activity in lung tissue homogenates at several time points (T0, 0 min; T1, 60
min; T2, 120 min; T3, 180 min; and T4, 240 min), and to measures changes in lung
tissue wet/dry weight ratio (W/D), apoptosis index (AI), and Hsp90a expression
and organization at T2, T3 and T4. Comparing group C with groups E1 and E2, the
levels of SOD activity and MDA were not significantly different at T0 and T1
(P>0.05); W/D ratio and AI were significantly higher than in groups E1 and E2
(P<0.05, P<0.01); 120 min after LIR, MDA, W/D ratio, and AI were lower than in
groups E1 and E2 (P<0.05, P<0.01). MDA, W/D ratio and AI were lower in E2 than in
E1 (P<0.05), and SOD and Hsp90a expression increased (P<0.05). The ultrastructure
in group E showed less injury compared with group C. In conclusion, by scavenging
oxygen free radicals, OMT can inhibit apoptosis, increase Hsp90a expression, and
reduce the injury caused by lung ischemia reperfusion.
PMID- 28413482
TI - Dysfunction of the thymus in mice with hypertension.
AB - The aim of this study was to evaluate thymus function in mice with hypertension.
A total of 60 C57BL/6J mice were randomized into control, sham surgery and two
kidney, one-clip groups (n=20 in each). At 4 or 8 weeks after surgery, mice were
sacrificed, and blood, spleens, kidneys and thymuses were harvested. The results
of reverse transcription-quantitative polymerase chain reaction analysis revealed
that the mRNA levels of Forkhead box protein N1 (Foxn1) and autoimmune regulator
(AIRE) in the thymus tissue of mice from the HTN group were significantly lower
than those from the control group at 4 and 8 weeks (P<0.05). Foxn1 and AIRE
expression was also reduced in the sham surgery group at 4 weeks after surgery,
but had recovered 4 weeks later. Similar results were observed for the expression
of signal-joint T cell receptor excision circles and the percentages of T cell
subsets. The present study indicates that impaired thymus function is associated
with hypertension in mice, which suggests that thymus function may be a novel
target for the treatment of patients with hypertension.
PMID- 28413483
TI - Morphine and pregabalin in the treatment of neuropathic pain.
AB - The drugs that are currently available to treat neuropathic pain exhibit
inadequate efficacy and numerous adverse effects. The present study compared the
efficacy of combination therapy with pregabalin and morphine with that of each as
a single agent in patients with neuropathic pain. The primary measurement was
mean daily pain intensity. Secondary measurements included a pain questionnaire,
adverse effects, mood and quality of life. Combination therapy of morphine plus
pregabalin and morphine monotherapy were both more effective at reducing
neuropathic pain than pregabalin monotherapy. Furthermore, patients in the
combination group noted that their quality of life markedly improved from the
baseline, as compared with the patients in the other two groups. These findings
indicate that combination therapy with morphine and pregabalin may be used as a
valuable therapy for neuropathic pain.
PMID- 28413484
TI - Inhibitor kappaBalpha protein therapy alleviates severe pneumonia through
inhibition of nuclear factor kappaB.
AB - To investigate the effect of inhibitor kappaBalpha (IkappaBalpha) on severe
pneumonia and explain the mechanisms of nuclear factor kappaB (NF-kappaB), the
activation of NF-kappaB was induced in Sprague-Dawley (SD) rats infected with
Klebsiella pneumoniae (K. pneumoniae). The rats were then treated with differing
concentrations of IkappaBalpha protein. A histological analysis was performed to
compare the lung structure prior to and following treatment, and an
immunohistochemistry assay was used to detect NF-kappaB activity. In addition,
the expression of certain inflammatory factors was detected using a protein chip
assay. The severe pneumonia rat model was successfully produced and in model
rats, NF-kappaB was activated by K. pneumoniae. Following treatment with
IkappaBalpha, the activity of NF-kappaB was inhibited and pneumonia symptoms in
model rats were alleviated. Furthermore, the expression of a number of
inflammatory factors including tumor necrosis factor alpha (TNF-alpha),
interleukin 6 (IL-6), interferon gamma (IFN-gamma) and monocyte chemoattractant
protein-1 (MCP-1) were also inhibited. The current study demonstrates that NF
kappaB inhibition with IkappaBalpha protein therapy prevents the development of
pneumonia in a K. pneumoniae rat model. The therapeutic effect is indicated by
the responses of proinflammatory factors, including TNF-alpha, IL-6, IFN-gamma
and MCP-1.
PMID- 28413485
TI - Therapeutic efficacy of phentolamine in the management of severe hand, foot and
mouth disease combined with pulmonary edema.
AB - The aim of this study was to examine the effects of phentolamine on severe hand,
foot and mouth disease (HFMD) combined with pulmonary edema (PE). From May 2008
to December 2012, 53 children with severe HFMD plus PE were enrolled in the
treatment group, receiving phentolamine intravenously at a loading dose of 5
ug/kg/min. The control group comprised 52 children with the same disease who did
not receive phentolamine infusion. Data concerning creatine kinase (CK), CK-MB,
cardiac troponin I (cTnI), heart rate, systolic blood pressure (SBP) and the
duration of ventilation dependence and hospitalization were collected. Adverse
events were also recorded. It was found that the phentolamine-treated patients
exhibited significantly lower CK, CK-MB and cTnI levels, heart rate and SBP than
the controls (P<0.01 for all parameters). The average duration of ventilator
dependence and hospitalization was significantly shorter (P<0.01) in the
phentolamine group than in the control group. It was also found that the overall
mortality rate was lower in the phentolamine group (5.8%) than in the control
group (11.5%). No adverse events were observed in either group. Thus, these
results offer preliminary evidence that phentolamine reduces mortality and
relieves the symptoms of EV71-induced PE. Phentolamine is a potential therapeutic
agent for this highly lethal disorder.
PMID- 28413486
TI - Cigarette smoke extract promotes proliferation of airway smooth muscle cells
through suppressing C/EBP-alpha expression.
AB - Cigarette smoke has been considered a major contributor to the pathogenesis of
chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth
muscle layer has been observed to be markedly thickened and the proliferation of
airway smooth muscle cells (ASMCs) was therefore used by the present study as a
model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed
to various concentrations of CSE and the proliferation of the cells was analyzed
by an MTT assay. Furthermore, the expression levels of calreticulin and
CCAAT/enhancer-binding protein alpha (C/EBP-alpha) in CSE-stimulated ASMCs were
determined by polymerase chain reaction and western blot analyses. In addition,
the effects of RNA interference (RNAi) to knockdown calreticulin and/or C/EBP
alpha on ASMC proliferation were studied. CSE was found to promote the
proliferation of ASMCs, which was associated with increased expression of
calreticulin and decreased expression of C/EBP-alpha. Knockdown of calreticulin
resulted in the upregulation of C/EBP-alpha and inhibition of cell proliferation,
while simultaneous knockdown of C/EBP-alpha promoted cell proliferation. The
present study revealed that CSE promoted the proliferation of ASMCs, which was
mediated by inhibition of C/EBP-alpha. These findings shed new light on airway
remodeling in COPD and may provide novel approaches for therapies.
PMID- 28413487
TI - Vandetanib and ADAM inhibitors synergistically attenuate the pathological
migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF
mediated MAPK pathway.
AB - The extracellular signals induced by vascular endothelial growth factor (VEGF)
are implicated in choroidal neovascularization (CNV) and thus, are associated
with vision-limiting complications in the human retina. Vandetanib is an oral
anticancer drug that selectively inhibits the activities of VEGF receptor and
epidermal growth factor receptor tyrosine kinase; however, the effects of
vandetanib on VEGF in retinal pigment epithelial (RPE) cells have not yet been
studied. In the present study, a combined treatment of vandetanib and a
disintegrin and metalloproteinase (ADAM) protein inhibitors were used to assess
the regulation of Epstein-Barr virus (EBV)-infected ARPE19 cells (ARPE19/EBV)
migration as a model of CNV. Vandetanib suppressed the expression of the
mesenchymal markers ADAM10 and ADAM17 in ARPE19/EBV cells, and also upregulated
epithelial cell markers of the RPE cells, E-cadherin and N-cadherin. The
migratory activity of ARPE19/EBV induced by VEGF was efficiently blocked by
vandetanib. Furthermore, co-treatment with vandetanib and an ADAM10 inhibitor
(GI254023X) or ADAM17 inhibitor (Marimastat) synergistically prevented migration
and the expression of vimentin, Snail and alpha-smooth muscle actin by regulating
extracellular signal-regulated kinase and p38 mitogen-activated protein kinase.
These results suggest that a combination treatment of vandetanib and ADAM
inhibitors may be developed as a novel therapeutic regimen to control retina
neovascular disease.
PMID- 28413488
TI - The effects of GLP-1 analogues on pre-diabetes of the children.
AB - The aim of the study was to evaluate the clinical efficacy of glucagon-like
peptide-1 (GLP-1) analogues in children of pre-diabetes to delay or reverse the
development of pre-diabetes into the state of diabetes by early intervention.
Prospective and randomized controlled clinical trials were performed in 42 cases
of newly diagnosed pre-diabetes in children. The sample size was randomly divided
into the two groups. The first group included 21 subjects comprising the
lifestyle intervention group, i.e., control group, and the second group included
21 subjects comprising the lifestyle intervention+GLP-1 analogues liraglutide
group, i.e., observation group. Interventions carried out lasted 3 months. A
review of intervention was carried out at 1 month and after 3 months. Medical
examinations were carried out at the the time following diagnosis with pre
diabetes and after the intervention of 3 months. The medical test examinations
included the fasting blood glucose (FPG), 2-hour postprandial blood glucose
(2hPG), detection of glycated hemoglobin A1c (HbA1C), total cholesterol (TC),
triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density
lipoprotein cholesterol (HDL-C), body mass index (BMI), insulin resistance (IR)
and the islet cell functions. After 1 month of intervention, the observation
group exhibited a better control on FPG and 2hPG compared with the control group
(P<0.05). After 3 months of the intervention, FPG and 2hPG levels of the
observation group were significantly lower than those of the control group
(P<0.01). The levels of HbA1C, TC, TG, LDL-C, HDL-C, and BMI of the observation
group were statistically better controlled, when compared with the control group
after the intervention of 3 months. The IR index of the observation group was
significantly decreased compared to that of the control group (P<0.05) and the
islet function index of the beta-cell of the observation group showed
statistically higher values than that of the control group (P<0.05). In
conclusion, GLP-1 analogues are a better regulator of blood sugar levels,
effectively improve lipid profile, body mass, IR and islet beta-cell function.
Furthermore, GLP-1 analogues opens up a new way to intervene pre-diabetes in
children.
PMID- 28413489
TI - Retrospective review of epidemic viral pneumonia cases in Turkey: A multicenter
study.
AB - Influenza A (H1N1) caused its first pandemic in 2009 in USA and Mexico. Since
then, clinicians have exercised great care in order to make an early diagnosis of
viral pneumonias. This is due in part to pandemic influenza A infection having
greater impact on populations <65 years old than other viral strains, including
seasonal influenza. Chest radiographies of those affected displayed a rapid
progression of patchy infiltrates, and a large proportion of individuals required
admission to intensive care units (ICU). Despite efforts, patients infected with
the virus had a high mortality rate. The present multicenter study aimed to
retrospectively evaluate the clinical, demographic and prognostic characteristics
of patients diagnosed with epidemic viral pneumonia in Turkey. A total of 92
patients were included in the study. The Student's t-test and Chi-square tests
were performed to analyze quantitative data, assuming a normal distribution, and
to analyze qualitative data, respectively. Stepwise logistic regression was used
to evaluate the effects of demographic variables and laboratory values on the
virus mortality rate. The male/female ratio was 42/50 and the mean age was
48.74+/-16.65 years. A total of 69 (75%) patients were unvaccinated against
influenza. The most common symptoms were cough (87%) and fever (63%). Chest
computed tomography showed peripheral patchy areas of the lungs of ground glass
density in 38 patients (41.3%). A total of 22 (59.4%) patients had H1N1, 5
(12.5%) patients had influenza B, and 38 (41.3%) patients met the criteria for
admission to the ICU. Of these patients, 20 (52.63%) were monitored with a
mechanical ventilator, with a noninvasive ventilator being adequate for 10
(26.32%) of patients. The length of stay in the ICU was 6.45+/-5.97 days and the
duration of mechanical ventilation was 5.06+/-4.69 days. A total of 12 (13.04%)
patients in the ICU succumbed. Logistic regression analysis revealed that among
the parameters possibly associated with mortality, being an active smoker
increased the risk of mortality 7.08-fold compared to other groups (P=0.005). In
conclusion, viral pneumonia remains a significant health problem during the
winter period. Considering the high number of ICU admissions and high rate of
mortality for patients in the present study, earlier initiation of antiviral
therapy is necessary. Active smoking increased mortality in viral pneumonia.
PMID- 28413490
TI - Noninvasive cumulative axial load may induce intervertebral disc degeneration-A
potential rabbit model.
AB - Intervertebral disc degeneration (IDD) is considered to be the main cause of many
spinal disorders; however, its underlying pathophysiology is not clearly
understood. Recent studies indicate that excessive mechanical loading may serve a
major role in the initiation of IDD. The aim of the present study was to explore
the effect of noninvasive cumulative axial loading on the intervertebral discs of
the lumbar spine using a novel rabbit model. Rabbits in the experimental group
were placed into individual tubes specifically designed to force maintenance of
an upright posture and were loaded with a heavy collar to increase the
intradiscal pressure of their lumbar spine. Radiograph imaging and magnetic
resonance imaging (MRI) was performed every 4 weeks to provide evidence of disc
degeneration. At the end of the experiment, the animals were sacrificed and disc
specimens were harvested for quantitative polymerase chain reaction and
histological analysis. MRI results revealed significant and progressive
reductions in the signal intensities of lumbar discs in the experimental group
compared with the control group throughout the 14-week study period. The
expression level of type I collagen was significantly increased and the
expression levels of type II collagen and aggrecan were significantly decreased
in the experimental group compared with the control group (P<0.05). Histological
examination revealed marked structural changes in the experimental group,
including fibrocartilage-like tissue ingrowth and accelerated fibrotic changes of
the nucleus pulposus. The results of the present study indicate that noninvasive
cumulative axial load is able to induce accelerated degenerative changes in
rabbit lumbar discs, which may provide useful information for the establishment
of a novel animal model of IDD for the research of IDD in humans.
PMID- 28413491
TI - Upregulated unique long 16 binding protein 1 detected in preeclamptic placenta
affects human extravillous trophoblast cell line (HTR-8/SVneo) invasion by
modulating the function of uterine natural killer cells.
AB - Well-controlled trophoblast invasion at the maternal-fetal interface is crucial
for normal placentation and successful pregnancy, otherwise pathological
conditions of pregnancy occur, such as preeclampsia. In previous studies, it has
been demonstrated that unique long 16 binding protein (ULBP)1, a ligand for the
natural-killer group (NKG)2D receptor on uterine natural killer (uNK) cells, is
upregulated in the placenta in patients with preeclampsia. As they are present on
the majority of the decidua, uNK have an important role in pregnancy. The aim of
the present study was to determine the role of ULBP1 in trophoblast cell
invasion, which is closely associated with the occurrence of preeclampsia. In the
present study, ULBP1 expression levels in placentas collected after cesarean
section from women with preeclampsia and normal pregnant women were determined by
immunohistochemistry, reverse transcription-quantitative polymerase chain
reaction and western blotting. The effects of ULBP1 on extravillous trophoblast
cell line (HTR-8/SVneo) invasion mediated via uNK cells and the underlying
mechanisms were investigated. mRNA and protein expression levels of ULBP1 were
significantly upregulated (P<0.05) in preeclamptic placentas compared with normal
controls. ULBP1 inhibited HTR-8/SVneo cells via the regulation of biological
functions of uNK cells, including the downregulation of NKG2D expression on uNK
cells and the stimulation of production of cytokines and chemokines that affect
extravillous cytotrophoblast invasion by uNK cells. ULBP1 may have an important
role in the pathophysiology of preeclampsia through the modification of
biological functions of uNK cells, which may affect trophoblast invasion.
PMID- 28413492
TI - Immunogenicity of insulin-producing cells derived from human umbilical cord
mesenchymal stem cells.
AB - Mesenchymal stem cells (MSCs) have been considered as hypo-immunogenic and
immunosuppressive. However, a thorough understanding of the immunological
properties after MSC differentiation in vitro and in vivo has not been reached.
We asked whether it would be immunogenic after differentiation or influenced by
the immune microenvironment after transplantation. In different disease models,
the immunological changes of MSCs after differentiation greatly varied, with
contradicting results. In order to clarify this, we used a modified four-step
induction method to induce human umbilical cord MSCs (hUCMSCs) to differentiate
into insulin-producing cells (IPCs), and investigate the immunological changes
after differentiation and immune reactions after transplantation into diabetic
mice. We found that the induced IPCs are hypo-immunogenic, lacking HLA-DR, CD40
and CD80 expression. Of note, we observed immune cell infiltration to peritoneal
cavity and left kidney capsule after local transplantation of induced IPCs. This
indicated that hUCMSC-derived IPCs maintained hypo-immunogenic in vitro, but
became immunogenic after transplanting to the host, possibly due to the changes
of immune microenvironment and thereafter immunological enhancement and immune
cell infiltration.
PMID- 28413493
TI - TGF-beta1 and TIMP1 double directional rAAV targeted by UTMD in atherosclerotic
vulnerable plaque.
AB - In the present study, we determined whether ultrasound-targeted microbubble
destruction (UTMD) combined with dual targeting of transforming growth factor
(TGF)-beta1 and tissue inhibitors of metalloproteinase (TIMP) 1 recombinant adeno
associated virus (rAAV) can stabilize atherosclerotic vulnerable plaques. First,
we used rabbit model to detect the TGF-beta1/TIMP1 virus therapy result. H&E
staining was used to evaluate the tissues. The protein levels of TGF-beta1 and
TIMP1 were detected in rabbit models. The THP-1 cells were induced into
macrophages, and transfected with TGF-beta1 and TIMP1 rAAV under optimized UTMD.
The expression of TGF-beta1 and TIMP1 was measured by RT-PCR and western
blotting. We found that the apoptotic rates were induced when compared to the
control group. The rAAV virus group showed a significant decrease in the p-ERT
and p-AKT expression. These data support the hypothesis that TGF-beta1 and TIMP1
are crucial in the regulation of atherosclerotic plaques.
PMID- 28413494
TI - Preoperative QCT assessment of femoral head for assessment of femoral head bone
loss.
AB - We quantified differences in trabecular volumetric bone mineral density (BMD) of
the femoral head between patients with proximal femoral fractures and healthy
subjects in the control group by using quantitative computed tomography (QCT)
with the purpose of providing guidance for the choice of head screw in the
intramedullary nail fixation. Participants suffering from intertrochanteric
fractures (n=536 patients) were recruited. In addition, 497 fracture-free, age
matched cases were considered as the control group. The volumetric BMD of
different regions of interest (ROI) in the proximal femur scanned by QCT were
analyzed between the fracture and control groups. BMD of proximal femur in the
fracture group was markedly lower than that in the control group. There were
significant differences at distinct regions for male and female between the two
groups. Furthermore, the trend of BMD changes among the femoral head, femoral
neck and intertrochanter were not parallels in terms of their average value. In
conclusion, osteoporosis has been demonstrated to be a main risk factor of the
proximal femoral fracture. BMD value of proximal femur was often inconsistent
with that of femoral head. Given this, preoperative QCT assessment plays an
important role in choosing proper head screw in the intramedullary nail fixation.
PMID- 28413495
TI - Perioperative application of salvianolate on oxidative stress and plasma IMD/ADM2
in patients with acute myocardial infarction undergoing PCI.
AB - The present study was conducted to investigate the effects of salvianolate on
perioperative oxidative stress and plasma Intermedin/adrenomedullin 2 (IMD/ADM2)
in patients with acute myocardial infarction (AMI) undergoing percutaneous
coronary intervention (PCI). The clinical data of 108 patients with AMI treated
by PCI were retrospectively analyzed. According to the use of salvianolate in
perioperative period, the patients were divided into the study group (n=62) and
the control group (n=46). The control group was given routine treatment while the
study group was given routine treatment combined with intravenous infusion of
salvianolate (200 mg administered once at 24 h before operation, once/day after
operation, 1 week later, the curative effect was observed). The changes in levels
of hemodynamic indexes [fibrinogen (FIB), platelet aggregation rate (PAG), plasma
viscosity, packed-cell volume (PCV)], oxidative stress indexes [superoxide
dismutase (SOD), glutathione peroxidase (GSH Px)], cardiac function indexes [left
ventricular ejection fraction (LVEF), cardiac output (CO)], related biochemical
indexes [high-sensitivity C-reactive protein (hs-CRP), N-terminal pro brain
natriuretic peptide (NT proBNP)] and plasma IMD/ADM2 in the two groups at 24 h
pre-operation and the 8th day postoperation were analyzed. On the 8th day post
operation, hemodynamic indexes such as FIB (3.3+/-1.0 and 3.9+/-0.9) g/l, PAG
(20.6+/-6.5 and 41.6+/-7.7)%, plasma viscosity (1.1+/-0.5 and 1.7+/-0.6)
mPa*s/120 s-1 and PCV (40.0+/-3.8 and 45.5+/-3.7)%, the related biochemical
indexes such as hs-CRP (55.1+/-4.8 and 79.3+/-5.3) mg/l and NT-proBNP (435.6+/
305.2 and 788.6+/-310.8) ng/l in the two groups were significantly decreased
compared to those pre-operation; the differences were statistically significant
(P<0.05). The oxidative stress indexes such as SOD (43.6+/-1.9 and 24.2+/-2.0)
U/ml and GSH-Px (822.6+/-13.52 and 742.6+/-62.6) enzyme activity unit, the
cardiac function indexes such as LVEF (45.1+/-3.5 and 41.9+/-3.3)% and CO (4.6+/
0.5 and 4.1+/-0.5) l/min and plasma IMD/ADM2 (163.5+/-20.2 and 144.2+/-22.5)
pg/ml in the two groups were significantly increased compared to those pre
operation; the differences were statistically significant (P<0.05). In
conclusion, applying intravenous infusion of salvianolate in patients with AMI
during perioperative period of PCI can effectively improve the oxidative stress
reaction and have positive effects on regulating plasma IMD/ADM2 level, which
promoted cardiac function recovery and enhances myocardial perfusion volume.
PMID- 28413496
TI - Clinical observation of the efficacy of Bevacizumab combined with argon green
laser in treating fundus macular edema.
AB - We studied the clinical efficacy of Bevacizumab combined with argon green laser
in treating fundus macular edema. From May 2009 to April 2013, 78 patients
seeking treatment for macular edema in the First Affiliated Hospital of Nanchang
University were enrolled in this study. Patients were randomly divided into two
groups: i) The experimental group (n=39) and the control group (n=39). Patients
in the experimental group were treated with Bevacizumab (Avastin(r)) combined
with argon green laser, and those in the control group were treated exclusively
with argon green laser. Therapeutic effects were compared, and postoperative
adverse reactions caused by both treatment methods were compared. Our results
showed that, after treatment, the macular foveal thickness was reduced noticeably
in both groups, while the therapeutic effect of combined treatment was more
prominent. Patients in the experimental group gained the best-corrected visual
acuity after one month of treatment, while patients in the control group achieved
that after three months of treatment. We concluded that the use of Avastin(r)
combined with argon green laser was safe and effective. Visual acuity was
improved obviously with minimum adverse reactions.
PMID- 28413497
TI - Antibiotic de-escalation principle in elderly patients with chronic obstructive
pulmonary disease complicated with severe pneumonia.
AB - The present study investigated the clinical effect of antibiotic de-escalation
therapy in elderly patients with chronic obstructive pulmonary disease (COPD)
complicated with severe pneumonia. According to the parity method of
hospitalization number, 86 cases were selected and divided into the observation
and control group with 43 cases each. Based on empirical antibiotic application,
levofloxacin and cephalosporin antibiotics were used in the control group. After
treatment for 3 days, the regimen was adjusted to antibiotics active against Gram
positive (G+) and Gram-negative (G-) bacteria such as the third or fourth
generation cephalosporin antibiotics, combined with aminoglycoside, or macrolide
antibiotics according to their effects. The treatment effects were re-evaluated
after 3-7 days. Finally, broad-spectrum antibiotics such as imipenem were chosen
or adjusted by bacterial cultures and drug sensitivity results in the control
group. Patients in the observation group were treated according to the principle
of antibiotic de-escalation therapy. Antibiotics active against G+ and G-
bacteria were chosen as the first round of medication. After 3 days, broad
spectrum antibiotics such as imipenem were added to the treatment regimen. After
7 days, the treatment was changed to narrow spectrum antibiotic administration if
the disease was in remission, and the antibiotic regimen was adjusted based on
bacterial culture and drug sensitivity results. The treatment results were
compared. The mechanical ventilation rate, antibiotic courses, number of
antibiotics used, and mortality of the observation group were significantly lower
than those in the control group (P<0.05). After treatment, lung function
improved, partial pressure of oxygen and blood oxygen saturation increased, and
partial pressure of carbon dioxide decreased in both groups. The improvement of
all of the above parameters were more significant in the observation group
(P<0.05). After treatment, the ratio of neutrophils over white blood cells and C
reactive protein levels of the two groups decreased, respiratory failure index
(RFI) increased, and the changes were significantly more pronounced in the
observation group (P<0.05). In conclusion, following the antibiotic de-escalation
principle to treat older patients with COPD complicated with severe pneumonia can
reduce the number of antibiotics required, improve lung function and clinical
effects, and is safe and effective.
PMID- 28413498
TI - Dynamic variations of the peripheral blood immune cell subpopulation in patients
with critical H7N9 swine-origin influenza A virus infection: A retrospective
small-scale study.
AB - H7N9 influenza is a recently emerging infection with a high mortality rate. The
aim of the present study was to investigate dynamic fluctuations of peripheral
blood immune cell subgroups in patients with critical H7N9 infection. Flow
cytometry was used to assess the cells in whole blood samples from 9 cases. With
regard to the innate immune system, in the majority of patients, the natural
killer (NK) cell counts were similar to those of monocytes, which demonstrated a
gradual increase in the progression period and an early increase followed by a
reduction during recovery. B cells exhibited a reduction during progression and
were further decreased during recovery. The CD4+T cells of all patients decreased
during progression, and further decreased during recovery. By contrast, CD8+T
cells increased in the majority of patients in the progression stage, and
underwent an initial reduction followed by a gradual increase during recovery.
However, CD8+ programmed death (PD)-1+T cell and T helper (Th) 1 cell frequencies
demonstrated a moderate increase in all patients during the progression stage,
and regulatory T cell (Treg) frequencies tended to be reduced during progression
and increased during recovery. Notably, this preliminary data also showed that
the frequencies of B cells, Th2 cells and Th17 cells in the progression period
were higher than those in the recovery period. The frequencies of monocytes,
CD4+T cell, CD8+T cell, CD4+PD-1+T cells and CD8+PD-1+T cells in the progression
period were lower than those during recovery. In conclusion, different levels of
peripheral blood immune cell subgroups during the pathogenesis of H7N9 infection
may be associated with elimination of the virus and immune damage.
PMID- 28413499
TI - Identification a nonsense mutation of APC gene in Chinese patients with familial
adenomatous polyposis.
AB - Familial adenomatous polyposis (FAP; Mendelian of Inherintance in Man ID, 175100)
is a rare autosomal dominant disorder characterized by the development of
numerous adenomatous polyps throughout the colon and rectum associated with an
increased risk of colorectal cancer. FAP is at time accompanied with certain
extraintestinal manifestations such as congenital hypertrophy of the retinal
pigment epithelium, dental disorders and desmoid tumors. It is caused by
mutations in the adenomatous polyposis coli (APC) gene. The present study
reported on a Chinese family with FAP. Polymerase chain reaction and direct
sequencing of the full coding sequence of the APC gene were performed to identify
the mutation in this family. A nonsense mutation of the APC gene was identified
in this pedigree. It is a heterozygous G>T substitution at position 2,971 in exon
15 of the APC gene, which formed a premature stop codon at amino acid residue 991
(p.Glu991*). The resulting truncated protein lacked 1,853 amino acids. The
present study expanded the database on APC gene mutations in FAP and enriched the
spectrum of known germline mutations of the APC gene. Prophylactic
proctocolectomy may be considered as a possible treatment for carriers of the
mutation.
PMID- 28413500
TI - Enhancement of humoral and cell mediated immune response to HPV16 L1-derived
peptides subsequent to vaccination with prophylactic bivalent HPV L1 virus-like
particle vaccine in healthy females.
AB - Currently prophylactic HPV16/18 L1 virus-like particle (VLP) vaccines are
employed with great success for the prevention of HPV infection. However, limited
information is available regarding the immune responses against human
papillomavirus (HPV) 16/18 L1 subsequent to HPV16/18 L1 VLP vaccination,
primarily due to the lack of widely used assays for immune monitoring. The aim of
the present study was to identify HPV16 L1-derived B and T cell epitopes for
monitoring the immune responses after HPV16/18 L1 VLP vaccination in healthy
females. The levels of immunoglobulin G (IgG), IgE, IgA and IgM reactive to HPV16
L1-derived peptides were measured by multiplex bead suspension assay. Following
detailed B cell epitope mapping, T cell responses specific to HPV16 L1-derived
peptides were evaluated by an IFN-gamma ELISPOT assay. The levels of IgG, IgM and
IgA reactive to 20-mer peptides (PTPSGSMVTSDAQIFNKPYW) at positions 293-312 and
300-319 of HPV16 L1 were significantly increased in the plasma after 2, 7, and 12
months after first vaccination. Detailed epitope mapping identified the amino
acid sequence (TSDAQIFNKP) at position 301-310 of HPV16 L1 as an immunogenic B
cell epitope. In addition, T cell responses to an HLA-A2- and HLA-A24-restricted
epitope (QIFNKPYWL) at position 305-313 of HPV16 L1 were increased following
immunization, suggesting that the HPV16/18 L1-VLP vaccination as able to induce
specific immune responses in T and B cells simultaneously. The identified B and T
cell epitopes may be useful as a biomarker for monitoring the immune responses
subsequent to HPV16/18 L1 VLP vaccination. Thus, the present study may provide
novel information to improve the understanding of the immune responses to HPV16
L1.
PMID- 28413501
TI - USP39 regulates the growth of SMMC-7721 cells via FoxM1.
AB - The present study investigated ubiquitin specific peptidase 39 (USP39) gene
knockdown on SMMC-7721 cells in vitro and in vivo, and the role of USP39 in
regulating the growth of hepatocellular carcinoma (HCC). Two small interfering
RNAs (siRNA) were constructed, which targeted the USP39 gene and control
sequences were synthesized and inserted into a pGCSIL-GFP lentiviral vector. The
full length of USP39 cDNA was amplified by polymerase chain reaction (PCR) and
cloned into pEGFP-N2, and the recombinant plasmids were transfected into cells.
Knockdown efficiency and upregulation of USP39 was determined by reverse
transcription-quantitative PCR and western blotting. The impact of USP39 on the
growth of SMMC-7721 cells in vitro was examined using an MTT assay, colony
formation, flow cytometry (FCM) and immunohistochemical staining. The impact of
USP39 on the growth of SMMC-7721 cells in vivo was examined by assessing
tumorigenicity in nude mice. Western blotting was performed to examine the
mechanism of USP39 regulation on SMMC-7721 cell growth. Recombinant vectors
containing specific and scrambled USP39 siRNA sequences were constructed and
transfected into SMMC-7721 cells. USP39 knockdown inhibited cell proliferation
and colony formation in SMMC-7721 cells, while upregulation of USP39 promoted the
growth of tumor cells. FCM indicated that USP39 knockdown led to G2/M arrest and
induced apoptosis in SMMC-7721 cells. USP39 knockdown inhibited xenograft tumor
growth in nude mice and led to the downregulation of the transcription factor
Forkhead Box M1 (FoxM1). Gene expression of FoxM1 targets, including polo-like
kinase 1, cyclin B1 and centromere protein A also decreased following USP39
knockdown. The results suggest that knockdown of USP39 inhibits the growth of HCC
in vitro and in vivo, potentially through the induction of G2/M arrest by
regulating the pre-mRNA splicing of FoxM1.
PMID- 28413502
TI - Remifentanil functions in the adaptive protection of cardiac function following
ischemia.
AB - The present study aimed to investigate the effects of remifentanil during
adaptation followinsg myocardial ischemia, and its possible clinical
applications. Remifentanil was used during the simulation of adaptation following
ischemia, which was performed using a Langendorff heart perfusion system. A total
of 75 rats were divided into five groups, and the coronary flow, cardiac output
and the cardiac enzyme content in coronary effluent prior to ischemia and post
reperfusion were recorded. Electron microscopy was used to observe myocardial
ultrastructure, and the volume of aortic and coronary effluent was also measured.
The recovery of cardiac output upon reperfusion was significantly higher
following remifentanil treatment (91%), as compared with the ischemic control
group (78%; P<0.05). The coronary flow of the experimental group following
reperfusion decreased by 4 ml/min compared with the control group not exposed to
ischemia, whilst the coronary flow of the ischemic control group was reduced by
20-24 ml/min. Flameng scoring of the mitochondria demonstrated improved
mitochondrial ultrastructure following remifentanil treatment (score, 1.25+/
0.31), as compared the ischemic control group (score, 3.14+/-0.17). Lactate
dehydrogenase (LDH) levels in the remifentanil-treated group were significantly
lower at 10 and 30 min post-reperfusion (15.3+/-7.1 and 10.2+/-6.8 U/l,
respectively), as compared with the control group (29.7+/-8.3 and 20.6+/-6.8 U/l,
respectively; P<0.05). The results of the present study suggested that the
application of remifentanil following ischemia protected heart function via the
opioid receptors by reducing myocardial enzyme release, and attenuating ischemia
induced changes to the myocardial cell and mitochondrial structure.
PMID- 28413503
TI - Vector-mediated Tum-5 expression in neovascular endothelial cells for treating
hepatocellular carcinoma.
AB - Hypervascular hepatocellular carcinoma (HCC) is one of the leading causes of
cancer-associated mortality. Angiogenesis is an important contributor to HCC
progression and metastasis; therefore, inhibiting angiogenesis may be an
effective method of treating HCC. Tumstatin is a novel type of efficient
endogenous vascular endothelial cell growth inhibiting factor. The anti
angiogenic activity of tumstatin is localized to the 54-132 amino acid region
(Tum-5). In a previous study performed by our group, the gene fragment encoding
Tum-5 was cloned and inserted into a pLXSN retroviral vector. In the present
study, the anti-angiogenic effects of Tum-5 and the antitumor effects exerted by
the pLXSN-Tum-5 vector in vivo were investigated. The results demonstrated that
pLXSN-Tum-5 significantly inhibited the growth of human umbilical vein
endothelial cells compared with pLXSN, but had no obvious effect on HepG2 cell
growth. Moreover, the antitumor and anti-angiogenic activity of Tum-5 was
examined in vivo using a xenograft of H22 HCC cells. The results indicated that
pLXSN-Tum-5 significantly inhibited tumor growth following 5 injections over 10
days. The size and weight of tumors in the pLXSN-Tum-5 group were lower than
those in the saline and pLXSN groups. Furthermore, immunohistochemical analysis
with CD31 antibodies indicated that the average microvessel density in the pLXSN
Tum-5 group were significantly lower than that in the saline and pLXSN groups.
These results suggested that Tum-5 exerts its antitumor activity by suppressing
vascular endothelial cells. The gene fragment of Tum-5 may be developed as an
effective inhibitor of angiogenesis and used to treat patients with HCC.
PMID- 28413504
TI - Early initiation of argatroban therapy in the management of acute superior
mesenteric venous thrombosis.
AB - Acute superior mesenteric venous thrombosis (ASMVT) is an intractable disease
with poor prognosis. Argatroban, a direct thrombin inhibitor, may be a novel
anticoagulant method in the therapy of ASMVT. The aim of the present study was to
assess the efficacy and safety of early argatroban therapy in ASMVT patients. The
current retrospective study reviewed a consecutive series of ASMVT patients
receiving early argatroban therapy during hospitalization between March 2013 and
April 2014, with 18 ASMVT patients included in the study. Of these, 16 patients
without hepatic dysfunction underwent anticoagulant therapy with argatroban with
a mean dose of 1.57+/-0.34 ug/kg/min and a mean duration of 12.2+/-3.7 days,
while their activated partial thromboplastin time (aPTT) was elevated to 1.95+/
0.26 times the baseline value. In addition, 2 hepatic dysfunction patients
received therapy with a dose of 0.41 ug/kg/min and 0.46 ug/kg/min, and with aPTT
of 1.68 and 1.62 times the baseline value, respectively. Overall, 94% (n=17) of
the patients presented clinical improvement, while 88% (n=16) of patients
presented partially or completely dissolved thrombus in contrast-enhanced
computed tomography images. The incidence of surgery and bowel resection was 6%
(excluding 1 case with intestinal necrosis detected on admission). Furthermore,
11% (n=2) of patients experienced a bleeding episode, however no major bleeding
or mortality occurred during hospitalization. During the follow-up, the mortality
and the recurrence rate were 6% and 11%, respectively. In conclusion, early
initiation of argatroban treatment may be an effective and safe therapy in ASMVT,
manifesting efficient resolution of the thrombus, rapid improvement of symptoms,
low incidence of bowel resection and bleeding complication, and low mortality
rate.
PMID- 28413505
TI - Rare scar sarcoidosis: A case report.
AB - A 70-year-old female patient presenting with swelling and subcutaneous nodule
formation localized to the knee scars over a two-month period is presently
reported. Dermatological examinations found erythematous swelling and small
papules on the patient's knee scars, along with subcutaneous nodules beneath and
around the scars. Computer tomography of the chest region identified multiple
obscure tubercles in the lungs and swollen lymph nodes in the hilum pulmonis and
mediastinum. Skin biopsy revealed multiple non-caseating granulomas, which had
infiltrated the dermis. The patient was diagnosed with scar sarcoidosis as a
result of these observations. The onset of scar sarcoidosis is rare and,
therefore, not well understood; however, inflammatory alterations in preexisting
scars may be important indicators for disease onset.
PMID- 28413506
TI - Active efflux pump adeB is involved in multidrug resistance of Acinetobacter
baumannii induced by antibacterial agents.
AB - The aim of the present study was to investigate the resistance of Acinetobacter
baumannii, which was induced by cefepime (FEP), cefoperazone-sulbactam (SCF),
tazobactam (TZP), levofloxacin (LEV), amikacin (AK), imipenem (IPM), and
ciprofloxacin (CIP), in vitro. Multi-step drug resistance selection of 16 A.
baumannii strains was performed using seven antibacterial agents (FEP, TZP, CIP,
AK, IPM, SCF, and LEV). The minimum inhibitory concentration (MIC) was determined
using the agar dilution method. Random amplified polymorphic DNA polymerase chain
reaction was performed to analyze the genotypes and the carrying rates of aac(3)
I, aac(6')-I, ant(3)-I, aph(3)-Via, OXA-23, OXA-24, AmpC, TEM-1, metallo-beta
lactamase gene (IMP), armA, rmtA, rmtB, parC, gyrA and adeB. Expression of adeB
was determined using semi-quantitative reverse transcription-polymerase chain
reaction (Semi-qRT-PCR). Among the 16 strains, 15 strains with drug resistance
(93.8%) were obtained following in vitro induction. Notable increases (8- to 128
fold) were noted in the MIC and different genotypes were showed in RAPD of the
strains before and after performing the drug resistant test. PCR data revealed
significant differences (P<0.05) between the carrying rates of resistant genes
before and after drug induction, with the exception of rmtA, OXA-24, TEM-1, and
IMP. Significant increases were demonstrated in the comparative adeB grayscale in
strains that underwent drug induction when compared with the sensitive strains
(55.69+/-43.11% vs. 10.08+/-26.35%; P=0.001). Findings of the present study
suggest that the active efflux pump, adeB, has an important role in multidrug
resistance of the A. baumannii induced by antibacterial agents in vitro.
PMID- 28413507
TI - Anaphylactic shock caused by haemocoagulase injection in China.
AB - Haemocoagulase injection is a mixture of purified enzymes isolated from the venom
of Bothrops atrox, which is used for the prevention and treatment of haemorrhage.
It is a relatively safe pharmacological agent that does not require a skin test
prior to administration. However, following a literature search, 14 reported
cases of anaphylactic shock caused by haemocoagulase injection were identified,
including one lethal case in China. Using SDS-PAGE and protein identification,
four primary components in haemocoagulase injection were characterized, including
one metalloproteinase, which may be a thromboplastin-like enzyme, and two serine
proteinases, which may be thrombin-like enzymes. Administering concentrated
haemocoagulase injections failed to provoke a positive skin reaction in allergic
patients. Basophil activation tests revealed that haemocoagulase injections did
not upregulate cluster of differentiation 63 or C-C chemokine receptor type 3
expression. These findings suggest that haemocoagulase injection may cause fetal
anaphylaxis. Although it is difficult to determine a clear conclusion without
being able to evaluate the patients that underwent haemocoagulase injection
induced shock, it is unlikely that the venomous components of haemocoagulase
injection cross-react with common allergens in allergic patients. It is possible
that haemocoagulase injection-induced anaphylaxis is caused by its additive
components, such as mannitol and succinylated gelatin.
PMID- 28413508
TI - Comparative evaluation of copeptin and NT-proBNP in patients with severe acute
decompensated heart failure, and prediction of adverse events in a 90-day follow
up period: A prospective clinical observation trial.
AB - The present study compared the prognostic value of a marker, the C-terminal
section of the arginine vasopressin prohormone (copeptin), with N-terminal B-type
natriuretic peptide (NT-proBNP) in patients with severe acute decompensated heart
failure. A prospective, observational cohort study was conducted in a tertiary
care hospital and enrolled 129 patients with severe acute decompensated heart
failure. Clinicians were blinded to investigational markers except NT-proBNP, and
the study participants were followed up for 90 days. The end-point was a
composite of cardiovascular death or re-hospitalization due to decompensated
heart failure. Of the 129 patients enrolled, 47 reached the end-point and 82 were
in a stable condition during follow-up. Receiver operating characteristic curve
analysis revealed that the areas under curve for the prediction of adverse events
within 90 days were similar for copeptin [0.602+/-0.052; 95% confidence interval
(CI), 0.499-0.705], NT-proBNP (0.659+/-0.048; 95% CI, 0.565-0.753) and their
combination (0.670+/-0.050; 95% CI, 0.573-0.767). Kaplan-Meier survival analysis
showed that the predictive value of NT-proBNP regarding the probability of
survival was superior compared with that of copeptin (log-rank test for trend,
P=0.001 vs. 0.040). Furthermore, multivariate Cox proportional-hazards regression
analysis revealed that increased NT-proBNP and copeptin plasma concentrations
were significant independent predictors of adverse events. The present study
provided evidence that copeptin has similar predictive properties compared with
NT-proBNP regarding adverse events within 90-days in patients with severe acute
decompensated heart failure, but that copeptin may not provide superior 90-day
prediction compared to NT-proBNP.
PMID- 28413509
TI - Effects of siRNA-mediated suppression of HPV-11 L1 expression on the
proliferation and apoptosis of vaginal epithelial cells.
AB - The aim of the present study was to investigate the effects of human
papillomavirus (HPV) infection on the gynecological disease of vaginitis and to
demonstrate how the small interfering RNA (siRNA) method may be used for HPV
prevention in the clinic. Human vaginal epithelial cells were transfected with
HPV-11 L1 expression vector and siRNA-HPV-11 L1 vectors and a control group was
transfected with scrambled siRNA. Cell proliferation in each group was analyzed
using the MTT assay and the expression of apoptosis-associated proteins was
measured by western blot analysis. Compared with the control group, HPV-11 L1
mRNA and protein levels were significantly increased following transfection with
the HPV-11 L1 expression vector in cells (P<0.05), but this result was
significantly reversed by silencing of HPV-11 L1 (P<0.05). In addition, cell
proliferation in the HPV-11 group was lower than that in the control group;
however, cell proliferation was significantly increased in cells transfected with
silenced L1 compared with that in the control group (P<0.05). Furthermore,
silencing of HPV-11 L1 significantly decreased caspase-3 and caspase-9
expressions in cells, whereas the expression was increased in the HPV-11 L1 group
(P<0.05). The present study suggested that siRNA-mediated silencing of HPV-11 L1
may have potential therapeutic applications for treating gynecological diseases
associated with HPV-11 infection.
PMID- 28413510
TI - Association of white blood cell counts with left ventricular mass index in
hypertensive patients undergoing anti-hypertensive drug therapy.
AB - Although studies using animal models have demonstrated that nonhemodynamic
factors, including inflammatory cells and cytokines, contribute to left
ventricular hypertrophy (LVH), there is little clinical data to confirm this
association. Therefore in the present study, levels of circulating specific types
of leukocyte were measured to determine the association between white blood cells
and left ventricular mass index (LVMI) in hypertensive patients undergoing anti
hypertensive drug therapy. A total of 144 consecutive hypertensive patients
taking anti-hypertensive drug therapy were enrolled in the current study.
Subjects were divided into two groups: Those with normal geometry and those with
left LVH. Total white blood cells and differentiated subtypes (neutrophils,
lymphocytes, monocytes) were counted, and left ventricular end-diastolic
diameter, left ventricular posterior wall thickness in diastole and inter
ventricular septal wall thickness in diastole were all measured. Analysis
revealed a significant correlation between LVMI and total white blood cell levels
(P=0.013). The percentage of LVH in the highest tertile of WBC was increased
compared with the middle tertile (P=0.008). Furthermore, a significant
correlation between the highest tertile of neutrophil counts and LVH was observed
(P=0.039). However, no significant associations between LVMI and monocyte or
lymphocyte counts were detected. Therefore, the current study determined that
increased total white blood cell and neutrophil subtype counts were associated
with LVMI in hypertensive patients undergoing anti-hypertensive drug therapy.
They may provide convenient and useful markers for further risk appraisal of LVH
caused by nonhemodynamic factors of hypertension.
PMID- 28413511
TI - Application of dead space fraction to titrate optimal positive end-expiratory
pressure in an ARDS swine model.
AB - This study aimed to apply the dead space fraction [ratio of dead space to tidal
volume (VD/VT)] to titrate the optimal positive end-expiratory pressure (PEEP) in
a swine model of acute respiratory distress syndrome (ARDS). Twelve swine models
of ARDS were constructed. A lung recruitment maneuver was then conducted and the
PEEP was set at 20 cm H2O. The PEEP was reduced by 2 cm H2O every 10 min until 0
cm H2O was reached, and VD/VT was measured after each decrement step. VD/VT was
measured using single-breath analysis of CO2, and calculated from arterial CO2
partial pressure (PaCO2) and mixed expired CO2 (PeCO2) using the following
formula: VD/VT = (PaCO2 - PeCO2)/PaCO2. The optimal PEEP was identified by the
lowest VD/VT method. Respiration and hemodynamic parameters were recorded during
the periods of pre-injury and injury, and at 4 and 2 cm H2O below and above the
optimal PEEP (Po). The optimal PEEP in this study was found to be 13.25+/-1.36 cm
H2O. During the Po period, VD/VT decreased to a lower value (0.44+/-0.08)
compared with that during the injury period (0.68+/-0.10) (P<0.05), while the
intrapulmonary shunt fraction reached its lowest value. In addition, a
significant change of dynamic tidal respiratory compliance and oxygenation index
was induced by PEEP titration. These results indicate that minimal VD/VT can be
used for PEEP titration in ARDS.
PMID- 28413512
TI - Long-term statin use before primary percutaneous coronary intervention improves
treatment outcomes of acute myocardial infarction.
AB - Numerous studies have reported that high-dose statin loading therapy prior to
primary percutaneous coronary intervention (PPCI) improves the clinical outcomes
of patients following acute myocardial infarction (AMI). However, little is known
about the effects of long-term statin use prior to PPCI on such outcomes.
Therefore, the aim of the present analysis was to clarify the effects of long
term statin use before PPCI on the treatment outcomes of patients following AMI.
The records of 213 patients who had AMI and met the inclusion criteria were
retrospectively reviewed. Patients were divided into two groups: A control group
(n=178) who had received no statin pretreatment before AMI onset, and a statin
group (n=35) who had received statin treatment for >=1 month before AMI onset.
All patients received a standard treatment regimen for the secondary prevention
of coronary artery disease after PPCI. Baseline clinical variables, details of
the PPCI procedure and clinical outcomes within 3 months after treatment were
reviewed. Patients in the statin group were significantly older than those in the
control group (P=0.003). Compared with the control group, there was a greater
proportion of patients with hyperlipidemia and previous angina pectoris in the
statin group. There were no differences in the use of other drugs (aspirin, beta
blockers and angiotensin-converting enzyme inhibitors) prior to PPCI between the
two groups. The corrected TIMI frame count (cTFC) was significantly lower in the
statin group than in the control group (24.1+/-12.8 vs. 29.4+/-14.3,
respectively; P=0.043). Multivariable linear regression analysis showed that long
term statin use before AMI was a significant predictor of cTFC after PPCI
(P=0.012). Furthermore, the incidence of major adverse cardiac events within 3
months after PPCI was higher in the control group than in the statin group (16.8
vs. 2.9%, respectively; P=0.032). Logistic regression analysis showed that
previous statin use was associated with the incidence of major adverse cardiac
events within 3 months after treatment (P=0.012). The results of the present
study demonstrate that long-term statin use prior to PPCI improved treatment
outcomes after AMI in actual clinical practice.
PMID- 28413513
TI - Huperzine A inhibits immediate addictive behavior but not behavioral
sensitization following repeated morphine administration in rats.
AB - Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to
treat addiction. The current study aimed to examine the effects of huperzine A, a
cholinesterase inhibitor, on behavioral sensitization induced by repeated
morphine administration and relapse induced by contextual conditioning. The
present study also assessed whether the state-dependency hypothesis may explain
the results. Adult rats were divided into four groups (n=8) and intraperitoneally
injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for
5 days. The effect of repeated huperzine A administration alone on locomotor
activity was assessed. For the experiments that analyzed the development of
morphine-induced sensitization, 40 rats were divided into five groups (n=8):
Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine.
Following a withdrawal period of 7 days, all animals were administered saline or
morphine, as appropriate. To test the state-dependency hypothesis, the rats in
the Saline+Morphine group were injected with saline and morphine, while the other
three groups were administered different doses of huperzine A and morphine. To
examine the effect of huperzine A on the expression of morphine-induced
sensitization, the rats in huperzine A+Morphine groups were injected with
appropriate concentrations of huperzine A, and morphine. The current results
indicated that the administration of huperzine A alone did not affect locomotor
activity, while higher doses of huperzine A inhibited the addictive behavior
induced by morphine at the development phase. Additionally, huperzine A
administration during the expression phase of morphine sensitization did not
inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg
huperzine A inhibited the expression of morphine-induced behavioral
sensitization. Therefore, the results of the current study do not support the
state-dependency hypothesis.
PMID- 28413514
TI - Effect of pre-emptive analgesia by continuous femoral nerve block on early
postoperative cognitive function following total knee arthroplasty in elderly
patients.
AB - To the best of our knowledge, the effect of pre-emptively blocking pain
transmission on acute postoperative cognitive dysfunction (POCD) has not yet been
assessed. Therefore, the present study aimed to investigate the effect of pre
emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative
pain and early cognitive function following total knee arthroplasty (TKA) surgery
in elderly patients. CFNB was performed prior to TKA surgery in the pre-emptive
analgesia group (n=30) and following TKA surgery in the control group (n=30).
POCD was defined as a two-point reduction in the postoperative score compared
with the preoperative score in the mini-mental state examination. The visual
analog scale (VAS) was used to evaluate the intensity of pain at rest and during
exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia
group was significantly lower than in the control group (P<0.01). In the
preemptive analgesia group, VAS scores at three days post-surgery were lower than
those in the control group (P<0.01). The incidence of POCD on the third
postoperative day was slightly lower in the pre-emptive analgesia group compared
with the control group. In conclusion, the results demonstrate that pre-emptive
analgesia by CFNB may promote the recovery of early cognitive function following
TKA in elderly patients.
PMID- 28413515
TI - Outcome of out-of-hospital cardiac arrest after fibrinolysis with reteplase in
comparison to the return of spontaneous circulation after cardiac arrest score in
a geographic region without emergency coronary intervention.
AB - Coronary occlusion and pulmonary embolism are responsible for the majority of
cases of out-of-hospital cardiac arrest (OHCA). Despite previous favourable
results of pre-hospital fibrinolysis in cases of OHCA, the benefit could not be
confirmed in a large controlled study using the fibrinolytic tenecteplase. For
reteplase (r-PA), there are hardly any data regarding pre-hospital fibrinolysis
during ongoing resuscitation. The present study reported results using r-PA
therapy in a German physician-supported Emergency Medical Services system. The
data of OHCA patients who received pre-hospital fibrinolytic treatment with r-PA
after an individual risk/benefit assessment were retrospectively analysed. To
assess the effectiveness of this approach, the rate of patients with a return of
spontaneous circulation (ROSC) was compared with the corresponding figure that
was calculated with the help of the RACA (ROSC after cardiac arrest) score. The
RACA algorithm predicts the probability of ROSC based on data from the German
Resuscitation Registry. Further outcome data comprised hospital discharge rate
and neurologic status at discharge. From 2001 to 2009, 43 patients (mean age,
58.5 years; 65.1% male; 58.1% ventricular fibrillation) received r-PA. Of these,
20 patients (46.5%) achieved ROSC, compared to a probability of 49.8% according
to the RACA score (P=0.58). A total of 8 patients (18.6%) were discharged alive,
including 5 (11.2%) with a good neurological outcome. For the analysed small
patient collective, pre-hospital r-PA did not offer any benefits with regard to
the ROSC rate. Further analyses of larger patient numbers on a nationwide
registry basis are recommended.
PMID- 28413516
TI - A simple method of placing a coronary sinus catheter through the femoral vein in
miniature swine.
AB - The aim of the present study was to evaluate the feasibility of placing a
coronary sinus (CS) catheter through the femoral veins of miniature swine. A
total of 16 male domestic pigs (3-4 months old, 25+/-2 kg) were used. Firstly,
the anatomic structure of the CS ostium of swine heart was observed at different
angles under X-ray. The guide wire and Cobara catheter were subsequently advanced
into the right atrium through the femoral vein. Subsequently, the guide wire was
retracted behind the fix curve of the Cobara catheter and the catheter bent
spontaneously in the absence of supporting guide wire following retraction. The
catheter was then gently rotated clockwise to direct the catheter tip to the left
allowing the catheter to easily be placed in the CS ostium. This method was
associated with a short procedure time: The time on separation of the blood
vessels was 15.5+/-5.8 min and the time of radiation exposure was 112+/-20 sec.
The success rate of placing the catheter to CS ostium was 100%. Only one pig
experienced a hematoma after the sheath was pulled out. All swine recovered
without serious complications, such as perforation of coronary vein and
pericardial tamponade. Therefore, this method of placing CS catheter is simple,
safe and reliable, which may offer help for related research.
PMID- 28413517
TI - Isoflurane anesthesia induces liver injury by regulating the expression of
insulin-like growth factor 1.
AB - It has been suggested that isoflurane may cause perioperative liver injury.
However, the mechanism of its action remains unknown. The purpose of the present
study was to determine this possible mechanism. Sprague-Dawley rats were randomly
assigned into one of three groups (all n=12): Control group (exposed to mock
anesthesia), isoflurane group (exposed to 2% isoflurane for 90 min), and
isoflurane + insulin-like growth factor 1 (IGF-1) group (exposed to 2% isoflurane
for 90 min and then treated with IGF-1). Reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) and western blotting were conducted to
determine the levels of expression of IGF-1 and its receptor IGF-R. Liver
necrosis was assessed by histological examination. TUNEL assay was performed to
determine the apoptosis of hepatic cells. In addition, the levels of the proteins
caspase-3 and B-cell lymphoma-extra large (Bcl-xL) were measured. Compared with
the control group, levels of IGF-1 and IGF-1R mRNA and protein were significantly
decreased following exposure to isoflurane (all P<0.05). The necrosis rate and
liver apoptosis were significantly increased in the group treated with isoflurane
alone compared with the control group (P<0.05), but were significantly decreased
compared with the isoflurane group following application of IGF-1 (P<0.05).
Additionally, isoflurane exposure significantly increased levels of caspase-3
compared with the control group (P<0.05), but decreased levels of Bcl-xL
(P<0.05). By contrast, application of IGF-1 reversed these changes. The present
study therefore suggests that isoflurane induces liver injury in part by
regulating the expression of IGF-1 and that application of IGF-1 may protect
against liver injury induced by isoflurane exposure.
PMID- 28413518
TI - Effect of N-acetylglucosamine administration on cartilage metabolism and safety
in healthy subjects without symptoms of arthritis: A case report.
AB - N-acetylglucosamine (GlcNAc) is a widely accepted treatment for osteoarthritis
(OA); however, its effect on healthy individuals is poorly understood. To
evaluate the effect of GlcNAc administration on healthy subjects that do not
exhibit symptoms of arthritis, the present randomized, double-blind, placebo
controlled study was performed. In the present study, 68 male and female Japanese
participants, without symptomatic and radiographic evidence of OA, were enrolled
and randomly allocated to receive placebo or GlcNAc (500 or 1,000 mg/day) for 16
weeks. Effects were evaluated using biomarkers for type II collagen degradation
and synthesis, collagen type II cleavage (C2C), procollagen type II carboxy
terminal propeptide (PIICP) and their ratio (C2C/PIICP). Furthermore, safety
assessments were performed via physical parameters, hematology, blood
biochemistry and urinalysis. The results indicated that there was no significant
change in the biomarkers for type II collagen degeneration and synthesis during
and after the intervention with the placebo and two GlcNAc groups. However,
subgroup analysis using subjects with impaired cartilage metabolism (who
exhibited enhanced type II collagen degradation and reduced type II collagen
synthesis) indicated that the C2C levels were significantly decreased at 8
(P<0.05) and 16 (P<0.01) weeks during the intervention in the two GlcNAc (500 mg
and 1,000 mg/day) groups, compared with the placebo group. In contrast, PIICP
levels were not notably different in the placebo and two GlcNAc groups. The
C2C/PIICP ratio was markedly decreased at 12 and 16 weeks during the intervention
in the two GlcNAc groups, compared with the placebo group. Moreover, no
supplement-related adverse events were observed during and after the
intervention. In conclusion, these observations indicate that oral administration
of GlcNAc at doses of 500 and 1,000 mg/day improves cartilage metabolism in
healthy subjects without apparent adverse effects.
PMID- 28413519
TI - AMP-activated protein kinase mediates the effects of lipoprotein-associated
phospholipase A2 on endothelial dysfunction in atherosclerosis.
AB - The present study aimed to investigate the effects of lipoprotein-associated
phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an in vitro cell model
of atherosclerosis, and to determine whether AMP-activated protein kinase (AMPK)
mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392
patients with coronary artery disease (CAD), including various sub-conditions,
were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In
addition, an in vitro model of atherosclerosis was established by exposing human
umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein
(oxLDL). SB-435495 was used to inhibit Lp-PLA2, and compound C was used to
suppress AMPK expression. Lp-PLA2, AMPKalpha and phosphorylated-AMPKalpha (T172)
expression in HUVECs were evaluated using western blot analysis. The
concentrations of nitric oxide (NO), endothelin 1 (ET-1), intercellular adhesion
molecule 1 (ICAM-1) and platelet/endothelial cell adhesion molecule 1 (PECAM-1)
in cell culture supernatant were determined using commercially available ELISA
kits. MTT assays were employed to indicate changes in cell viability. The current
study found the plasma Lp-PLA2 levels were elevated in the CAD patients with
stable angina pectoris, unstable angina pectoris, acute coronary syndromes and
acute myocardial infarction, compared with a healthy control population. In
addition, the in vitro results showed that Lp-PLA2 expression levels were
elevated in oxLDL-exposed HUVECs. Lp-PLA2 suppression could increase cell
viability, induce the production of NO and decrease the secretion of ET-1, in
addition to suppressing the expression of cell adhesion molecules, including ICAM
1 and PECAM-1 in oxLDL-exposed HUVECs. The expression of AMPKalpha and
phosphorylated-AMPKalpha (T172) was regulated by Lp-PLA2, and AMPK suppression
was able to reverse the effects of Lp-PLA2 with regard to cell viability,
endothelial vasorelaxation capacity and the secretion of adhesion molecules in
oxLDL-exposed HUVECs. In conclusion, the present study provides initial evidence
that Lp-PLA2 is able to cause endothelial dysfunction in an in vitro model of
atherosclerosis, and the effects of Lp-PLA2 on endothelial dysfunction was at
least partially a result of the downregulation of AMPKalpha, thus contributing to
the progression of atherosclerosis.
PMID- 28413520
TI - Prognosis of patients with Acinetobacter baumannii infection in the intensive
care unit: A retrospective analysis.
AB - The present retrospective study aimed to investigate the prognostic factors for
critically ill patients with an Acinetobacter baumannii (A. baumannii) infection.
A total of 37 patients from the intensive care unit (ICU) were enrolled in the
study. Data was collected from patients, including age, gender, ethnicity, A.
baumannii infection status, concurrent infection status, prescribed antibiotics,
Acute Physiology and Chronic Health Evaluation II (APACHE II) and sepsis-related
organ failure assessment (SOFA) scores, procalcitonin level, site of infection,
shock, sepsis and renal replacement therapy status. Univariate and multivariate
analyses were performed to determine the prognostic factors for mortality. In
total, 8 out of the 37 patients included in this trial did not survive, resulting
in an ICU mortality rate of 21.6%. Univariate analysis indicated that, in
comparison with the survival group, APACHE II and SOFA scores were significantly
higher in the mortality group (P<0.002 and P<0.001, respectively). A larger
number of patients with septic shock were detected in the mortality group in
comparison with the survival group (n=4 and n=3, respectively), whereas a larger
number of patients were infected with multidrug-resistant A. baumannii (MDRAB) in
the survival group in comparison with the mortality group (51.9 and 14.3%,
respectively). However, the prognosis was not significantly influenced by
antibiotics administered, mixed infection or the site of infection. Multivariate
analysis demonstrated that the APACHE II score was the only independent factor
affecting the disease prognosis. Receiver operating characteristic curve analysis
of the APACHE II score demonstrated that the area under the curve was 0.845+/
0.078. In patients with an APACHE II score of 15, the sensitivity and specificity
predictions for mortality were 87.5% and 72.4%, respectively. The APACHE II score
at diagnosis was the only independent factor found to assist in the prognosis of
mortality for patients in the ICU with an A. baumannii infection. In conclusion,
the results of the present study demonstrated that the APACHE II score may
contribute towards the prognostic evaluation of patients in the ICU with an A.
baumannii infection.
PMID- 28413521
TI - Efficacy of arsenic trioxide drug-eluting stents in the treatment of coronary
heart disease.
AB - The aim of the current study was to evaluate the safety and clinical efficacy of
arsenic trioxide drug-eluting (AVI) stents, manufactured in China, for the
treatment of coronary heart disease (CHD). Between January and August 2014, 40
patients with CHD admitted to Yongchuan Hospital with implanted AVI stents alone
were selected. A one-year clinical follow-up was completed and one year
postoperative coronary angiography was reviewed. Major adverse cardiovascular
events (MACE), recurrent angina, stent restenosis and stent thrombosis cases were
detected. All 40 patients with CHD completed the one-year clinical follow-up, as
well as the one-year postoperative coronary angiography. The follow-up results
indicated that the MACE rate was 15.0% (6/40), the target lesion
revascularization rate was 15.0% (6/40), the angina recurrence rate was 32.5%
(13/40), the in-stent restenosis rate was 20.0% (8/40) and the stent thrombosis
rate was zero. There were no cases of cardiac death or nonfatal myocardial
infarction. The incidence of restenosis was higher following implantation of the
AVI stent and the safety and clinical efficacy were worse than expected.
PMID- 28413522
TI - Electroacupuncture combined with mosapride alleviates symptoms in diabetic
patients with gastroparesis.
AB - The present study compared the clinical effectiveness of electroacupuncture (EA),
monotherapy and combination therapy involving the administration of EA and
mosapride in diabetic patients with severe or mild symptoms suggestive of
gastroparesis. A total of 56 patients with type 2 diabetes who had symptoms
suggestive of gastroparesis for >3 months were divided into two groups according
to the Gastroparesis Cardinal Symptom Index (GCSI) score, including 33 in the
mild group (GCSI score <3.5) and 23 in the severe group (GCSI score >=3.5).
Initially, all patients received EA monotherapy for 14 days. An effective
response was defined as a reduction of the overall baseline GCSI score by >25%
after treatment. The non-responding patients then received a combination
treatment with EA and mosapride. Gastric emptying was assessed by the 13C
octanoic acid breath test at the beginning and end of each treatment session. Two
patients in the severe group dropped out of the study during the initial
treatment session. The results revealed that 34 early-responding patients (30
from the mild group and 4 from the severe group) treated with EA monotherapy, and
20 non-early-responding patients receiving combination therapy with EA and
mosapride showed clinically significant improvements. Analysis of data from the
mild subgroup demonstrated that EA treatment specifically improved symptoms of
nausea, vomiting, stomach fullness, excessive fullness and bloating. There was no
statistically significant difference in the gastric half-emptying time among
patients prior to and after EA monotherapy. These preliminary results suggested
that EA may be an option for improving mild symptoms in patients with diabetic
gastroparesis, whereas combination therapy involving EA and pharmaceutics is
required in patients with severe symptoms.
PMID- 28413523
TI - Predictors of visual outcome with transsphenoidal excision of pituitary adenomas
having suprasellar extension: A prospective series of 100 cases and brief review
of the literature.
AB - OBJECTIVE: The aim was to assess the factors influencing the visual outcome
following trans-sphenoidal excision of pituitary adenomas. MATERIALS AND METHODS:
One hundred consecutive patients of pituitary adenomas with suprasellar extension
(SSE) were operated by trans-sphenoidal approach from July 2003 to December 2006.
There were 52 male and 48 female patients with a mean age of 42.47 years. The
visual impairment score, which was used to evaluate the visual outcome was
produced by adding the scores for visual acuity and visual field defects of each
patient (from the tables of the German Ophthalmological Society). The mean
diameter, the SSE and the parasellar extension of the lesion were noted in the
magnetic resonance imaging study. The average follow-up was 43.5 months. RESULTS:
The mean diameter of the tumor was 32.97 mm, and the mean SSE was 14.95 mm. The
parasellar extension was present in 27 patients. The vision improved in 61 of the
71 patients (85.91%). The shorter the duration of visual symptoms and smaller the
size of the lesion resulted in better visual outcome. The age and the
preoperative visual impairment did not show any correlation with the visual
outcome. CONCLUSIONS: Patients with visual symptoms of <1-year duration (P <
0.01) and adenomas of <36.5 mm diameter (P < 0.009) have better visual outcome.
PMID- 28413524
TI - Perioperative complications in endovascular neurosurgery: Anesthesiologist's
perspective.
AB - BACKGROUND: Endovascular neurosurgery is known to be associated with potentially
serious perioperative complications that can impact the course and outcome of
anesthesia. We present here our institutional experience in the anesthetic
management of various endovascular neurosurgical procedures and their related
complications over a 10-year period. METHODS: Data was obtained in 240 patients
pertaining to their preoperative status, details of anesthesia and surgery,
perioperative course and surgery-related complications. Information regarding
hemodynamic alterations, temperature variability, fluid-electrolyte imbalance,
coagulation abnormalities and alterations in the anesthesia course was
specifically noted. RESULTS: Among the important complications observed were
aneurysm rupture (2.5%), vasospasm (6.67%), thromboembolism (4.16%), contrast
reactions, hemodynamic alterations, electrolyte abnormalities, hypothermia,
delayed emergence from anesthesia, groin hematomas and early postoperative
mortality (5.14%). CONCLUSION: Awareness of the unique challenges of endovascular
neurosurgery and prompt and appropriate management of the associated
complications by an experienced neuroanesthesiologist is vital to the outcome of
these procedures.
PMID- 28413525
TI - Post ventriculoperitoneal shunt abdominal pseudocyst: Challenges posed in
management.
AB - BACKGROUND: In patients with hydrocephalus, the abdominal cavity has been used
for absorption of cerebrospinal fluid (CSF) since 1905. Ventriculoperitoneal (VP)
shunt operation is followed by abdominal complications in about 5-47% cases.
Abdominal CSF pseudo cyst is an uncommon, but well described complication. AIM:
This survey was conducted to study the clinical profile and management of this
entity. We present our experience with cases of CSF pseudo cyst in children.
MATERIALS AND METHODS: Retrospective analysis of 4 cases diagnosed to have
abdominal pseudo cyst following VP shunt between 2008 and 2013. All the four
cases were suspected clinically and diagnosis was confirmed by abdominal
ultrasonography. RESULTS: In three patients, the cyst was multilocular and of
varying size. Fourth one had a unilocular cyst at the lower end of VP shunt. All
the four patients had features of varying degree raised intracranial pressure and
a two patients had abdominal signs also. All the patients needed open
exploration. Cyst fluid was drained and partial to complete excision of the cyst
was done along with the repositioning of the shunt in abdominal cavity in three
patients and exteriorization of shunt in one patient. Patients were followed for
any further complication over a period of 1-year. CONCLUSION: Abdominal pseudo
cyst is a rare complication after VP Shunt and could result in shunt malfunction
or abdominal symptoms and signs. Whenever suspected it should be confirmed by
imaging, followed by open exploration and repositioning of the shunt.
PMID- 28413526
TI - Neuroendoscopy - Is it safe?
AB - BACKGROUND: The effect of heat in endoscopic instruments used for laparoscopy and
hysteroscopy has been well-studied. Reports of thermal injury from nasal
endoscopes have also been reported. However, there are no experimental studies,
which have objectively documented and provided recommendations for safe use of
endoscopes in neurosurgery. OBJECTIVES: To study the heat generated at the tip of
the endoscope and the subsequent thermal damage caused to a cotton drape placed
in proximity, by varying the intensity of light delivered through different
optical cables, ambient (operating room) temperatures and working distances.
MATERIALS AND METHODS: The study was carried out in the operation theater using a
300 watt xenon light source connected to the endoscope with 3.5 mm and 4.8 mm
optical cables. A digital thermometer was used to record the heat generated at
the tip of the endoscope. RESULTS: The heat generated at the tip of the endoscope
reached its peak in the first 6 min and attained a plateau at 15 min after
turning on a light source of 60% intensity. Thermal injury to the cotton drape
took a longer time with a 3.8 mm cable compared with 4.8 mm cable. The heat
generated at the tip of the endoscope, and thereby the thermal injury caused was
found to be lower when the ambient temperature was close to 20 degrees C.
CONCLUSIONS: Complications related to thermal injuries caused by heat generated
at the tip of an endoscope can be reduced by using a smaller diameter cable,
light intensity of 60%, increasing the working distance (as permissible),
reducing the time spent for dissection while keeping the endoscope very close to
the target and lowering the ambient temperature to 20 degrees C.
PMID- 28413527
TI - First report of important causal relationship between the Adamkiewicz artery
vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid
hemorrhage: An experimental study using a rabbit model.
AB - BACKGROUND: The blood supply of the lower spinal cord is heavily dependent on the
artery of Adamkiewicz. The goal of this study was to elucidate the effects of
lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG)
cells secondary to Adamkiewicz artery (AKA) vasospasm. MATERIALS AND METHODS:
This study was conducted on 20 rabbits, which were randomly divided into three
groups: Spinal SAH (n = 8), serum saline (SS) (SS; n = 6) and control (n = 6)
groups. Experimental spinal SAH was performed. After 20 days, volume values of
AKA and neuron density of L4DRG were analyzed. RESULTS: The mean alive neuron
density of the L4DRG was 15420 +/- 1240/mm3 and degenerated neuron density was
1045 +/- 260/mm3 in the control group. Whereas, the density of living and
degenerated neurons density were 12930 +/- 1060/mm3 and 1365 +/- 480/mm3 in serum
saline (SS), 9845 +/- 1028/mm3 and 4560 +/- 1340/mm3 in the SAH group. The mean
volume of imaginary AKAs was estimated as 1,250 +/- 0,310 mm3 in the control
group and 1,030 +/- 0,240 mm3 in the SF group and 0,910 +/- 0,170 mm3 in SAH
group. Volume reduction of the AKAs and neuron density L4DRG were significantly
different between the SAH and other two groups (P < 0.05). CONCLUSION: Decreased
volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH
compared with controls. Increased degeneration the L4 dorsal root ganglion in
animals with SAH was also noted. Our findings will aid in the planning of future
experimental studies and determining the clinical relevance on such studies.
PMID- 28413528
TI - Clinical predictors for survival and treatment outcome of high-grade glioma in
Prasat Neurological Institute.
AB - OBJECTIVE: The aim was to identify clinical predictors for survival and examine
treatment outcome in patients with high-grade glioma (HGG). MATERIALS AND
METHODS: The authors retrospectively reviewed medical records of patients who was
diagnosed HGG between January 2007 and December 2009. Demographic data,
radiological data and treatment data of patients were reviewed and analyzed.
RESULTS: A total of 100 patients were analyzed. There was no difference in
demographic data between Grade III and IV glioma. Patients with HGG had median
survival time (MST) 18 months, The MST of patients with Grade III and IV glioma
were 26 and 13 months, respectively. In this study, only anaplastic
oligoastrocytoma and radiotherapy did impact strongly on survival of patients
with HGG. In patients with Grade III and IV glioma, radiotherapy found to have
influence on survival. CONCLUSION: Patients with HGG in Prasat Neurological
Institute had short survival resemble to other previous study. The clinical
predictors for survival of patients were identified on multivariate analysis.
PMID- 28413529
TI - An evaluation of neuroendocrine dysfunction following acute aneurysmal
subarachnoid hemorrhage: A prospective study.
AB - OBJECTIVE: The aim was to investigate the incidence and pattern of neuroendocrine
changes in cases of acute aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND
METHODS: Endocrine assessment was performed in 100 consecutive cases of acute
aneurysmal SAH presenting within 7 days of ictus. The gonadotropic,
somatotrophic, thyrotropic, and corticotrophic axes were evaluated for their
possible dysfunction. RESULTS: A total of 100 cases (38 males, 62 females; age
range - 17-76 years; mean age - 43.6 years) of acute SAH were studied. The
aneurysms were located in the anterior circulation (n = 95) and posterior
circulation (n = 5). The most common hormone deficiency was of growth hormone (n
= 67), followed by gonadotrophin (n = 50), corticotrophin (n = 49) and
thyrotrophin (n = 35). Hyperprolactinemia was noted in 10 cases. One-pituitary
hormone axis deficiency was noted in 26 cases while 67 cases had two or more
pituitary hormone axes dysfunction. A total of 93 cases had hormonal dysfunction
in one or more pituitary hormone axes, and seven cases had no hormonal
dysfunction. CONCLUSIONS: Endocrine dysfunction occurs in 93% cases of acute SAH
and multiple pituitary hormone axes dysfunction occurs in 67% cases. It is
suggested that hormonal evaluation should be considered as part of management of
acute SAH.
PMID- 28413530
TI - Outcome after operative intervention for traumatic brain injuries in the elderly.
AB - INTRODUCTION: The management of traumatic brain injuries in the elderly (age >=
65 years) is a constant dilemma. The aim of this study is to investigate for
factors that may predict outcome of operative treatment in this group of
patients. MATERIALS AND METHODS: A retrospective analysis was conducted on 68
elderly patients who had been operated in a designated center from 2006 to 2010.
Patients' age, Glasgow Coma score (GCS), pupillary responses, imaging findings,
medical conditions, and the use of anticoagulant/antiplatelet agents on patient
outcomes were studied. RESULTS: The overall mortality rate was 55.9%. Older age,
abnormal pupillary response, low GCS, the presence of midline shift and cistern
obliteration on computerized tomography were associated with poor survival.
Patient aged 75-84 with normal bilateral pupillary response still had an overall
survival rate of 52.6% and good outcomes (Glasgow outcome score: 4 or 5) in 36.8%
of patients. Abnormal pupillary response in at least one eye and preoperative GCS
<= 12 were associated with very poor prognosis. CONCLUSIONS: More advanced age
was found to be associated with progressively worse outcome. A subgroup patients
aged below 85 would survive and could achieve good clinical outcome. The
prognosis of those aged over 85 with moderate or severe head injuries was
extremely poor.
PMID- 28413531
TI - Unusual site of Rathke's cleft cyst: A case report and review of literature.
AB - We report an eight years female child of symptomatic giant Rathke's cleft cyst
extending from right parasellar, paraventricular region to right fronto-temporo
parietal cortical surface which is an unusual site for Rathke's cyst. MRI Brain
scans of patient who presented with diminution of vision in right eye with
headache and vomiting revealed a large cystic mass in right parasellar,
paraventricular region with peripheral enhancement and midline shift. In this
case, we performed the right fronto-temporo-parietal craniotomy with drainage and
marsupilization of cyst wall. Histopathologically, it was inflamed Rathke's cleft
cyst with focal epithelial metaplasia.
PMID- 28413532
TI - Spontaneous extradural and subgaleal hematoma: A rare neurosurgical crisis of
sickle cell disease.
AB - Extradural hematoma (EDH) in absence of trauma is a rare entity with only few
cases reported in literature. The various causes reported include: Vascular
malformation of dura, coagulopathies, sinus infection, middle ear or orbital
infection, and tumor. Occurrence of spontaneous EDH as a complication of sickle
cell disease is even much rarer. We report a case with sickle cell disease who
presented with spontaneous extradural and subgaleal hematomas following an
episode of vaso-oclusive crisis. He was managed successfully with surgery. The
association of epidural hematomas in sickling hemoglobinopathies is reviewed. In
all cases, we noticed one episode of sickle cell crisis just before the
occurrence of spontaneous EDH. Perhaps this crisis puts an extra demand over the
hematopoietic skull tissue disrupting inner and outer skull margins leading to
spontaneous EDH and subgaleal hematoma.
PMID- 28413533
TI - Persistent L5 lumbosacral radiculopathy caused by lumbosacral trunk schwannoma.
AB - Schwannomais, usually, benign tumor of nerve sheath that occurs evenly along the
spinal cord. Intra-pelvic schwannoma is very rare entity that may arise from
lumbosacral nerve roots or from sciatic nerve. Radicular pain of the lower limb
as a presenting symptom of pelvic schwannoma is extremely rare. In the current
report, the patient is presented with a right sided L5 radicular pain typical of
lumbar discopathy. Interestingly, a herniated lumbar disc was noted on
lumbosacral magnetic resonance imaging (MRI). In pre-operative studies a large
pelvic mass was detected in the right pre-sacral area with solid and cystic
components consistent with schwannoma. The patient underwent a low midline
laparotomy to evacuate the retroperitoneal mass. Uniquely, we found the tumor to
be arisen from lumbosacral trunk not from a root or peripheral nerve. Most cases
with intra-pelvic schwannoma present so late with vague abdominal and pelvic
discomfort or pain, low back pain, urinary and bowel symptoms because of
compressive effect of the tumor, or incidentally following gynecologic work-ups;
So, these patients are mostly referred to gynecologists and urologists. A
neurosurgeon should have a high degree of suspicion to diagnose such an entity
among his or her patients presented with pains typical for discopathy.
PMID- 28413534
TI - Malignant solitary fibrous tumour of orbit.
AB - Solitary fibrous tumor (SFT) is a rare neoplasm that is thought to be of
mesenchymal origin. Occurrence of such a tumor in the orbit is rare, more so in
its malignant form. Histopathologically, it can mimic several other tumors of the
orbit and can be differentiated by CD34 positivity. We report a case of malignant
transformation of an SFT of the orbit that recurred after 15 years. The
differentiating histopathological features with special stress on the importance
of CD34 positivity and principles of management are outlined. The need for long
term follow-up to detect recurrence and malignancy is stressed.
PMID- 28413535
TI - Third ventricular tuberculoma mimicking as a tumor: Report of a very rare case.
AB - Intracranial tuberculoma is a common neurosurgical problem in developing
countries; however, intraventricular tuberculoma is a rare entity. Here, we
report a rare case of third ventricular tuberculoma in a 21-year-old girl who
presented with features of raised intracranial pressure. Radiological findings
and management of third ventricular tuberculoma would be discussed and literature
regarding such lesions will be reviewed.
PMID- 28413536
TI - Primary cerebellopontine angle glioblastoma in an adult.
AB - Supratentorial glioblastoma is the most frequent primary intracranial tumor in
adults. Its localization in the cerebellum is extremely rare and such tumor
presenting as cerebellopontine angle (CPA) mass in an adult is even rarer. We
report the case of primary cerebellar glioblastoma in a 52-year-old woman who
presented clinically and radiologically as CPA mass. Its clinical presentation,
radiological findings, and treatment instituted are discussed in view of
pertinent literature.
PMID- 28413537
TI - Progressive hemiparesis in a young man: Hemicerebral atrophy as the initial
manifestation of basal ganglia germinoma.
AB - Basal ganglia germinomas are rare and patients are classically young Oriental
males presenting with gradually progressive hemiparesis. Although early treatment
with chemo-radiotherapy can be curative and significantly improve the quality of
life, medical attention is often delayed. A young Chinese male experienced a 6
month history of right hemiparesis with magnetic resonance imaging findings of
hemicerebral atrophy and lentiform nucleus microhemorrhage, highly suggestive and
early signs of basal ganglia germinomas. No further imaging was performed until 2
years later when he was admitted for acute neurological deterioration and a
repeat scan revealed a large infiltrative tumor pathologically confirmed to be a
pure germinoma.
PMID- 28413538
TI - Primary CNS vasculitis masquerading as glioblastoma: A case report and review.
AB - Isolated angitis of the central nervous system (IACNS)/primary angitis of central
nervous system vasculitis (PACNS) is an uncommon vascular disease, sparingly
presenting as an isolated inflammatory lesion on magnetic resonance imaging
(MRI). The disease usually manifests as a long-drawn and progressive ischemic
event. Delay in diagnosis due to focal nature of the lesion also contributes to
the poor prognosis as the dismal natural history and immunosuppressive therapy.
To date, only a few cases with tumor-like isolated angitis of CNS have been
reported with clear and definitive diagnostic workup.
PMID- 28413539
TI - A rare case of congenital glioblastoma with atypical presentation in an eleven
month-old infant: Case report with review of literature.
AB - Glioblastoma multiforme (GBM) is the most common and malignant primary brain
tumor in adults. The occurrence of this entity in infants is a rarity and
portends a uniform dismal prognosis and survival in spite of all the latest
available management options. The authors herein report a case of a GBM in an 11
month-old infant with tumor involving predominantly the left temporal and frontal
regions who expired 10 weeks after tumor decompression. Literature and available
management options have been reviewed in the context of the presented case.
PMID- 28413540
TI - Intraventricular glioblastoma multiforme mimicking meningioma and review of the
literature.
AB - Glioblastoma multiforme (GBM) is the most common primary brain tumor and is
usually found in aged persons in the cerebral hemispheres particularly the
frontotemporal region. But intraventricular GBM is rare and only few cases have
been reported in the literature. We report a case of a 27-year-old man who
presented with headache, vision loss in both eyes, and other signs and symptoms
of increased intracranial pressure. Computed tomography and magnetic resonance
imaging showed an intraventricular, well-circumscribed lesion with homogeneous
enhancement of contrast, suggestive of meningioma that is more common than GBM in
this location. The patient underwent surgical removal through transcortical
route. The final pathologic diagnosis was GBM. We present the clinical features,
radiological findings, and surgical management of this case and discuss the
pathogenesis and review of the literature of intraventricular GBM.
PMID- 28413541
TI - Clival giant cell tumor - A rare case report and review of literature with
respect to current line of management.
AB - Giant-cell tumor (GCT) involving the skull base is rare. Sphenoid bone is the
most commonly involved bone followed by petrous temporal bone. Histopathology and
radiological features of these lesions are similar to GCT involving bone
elsewhere. Unlike other sites, skull base is not an ideal site for the radical
surgery. Hence adjuvant treatment has pivotal role. Radiation therapy with
intensity-modulated radiation therapy, stereotactic radiosurgery or chemotherapy
with adriamycin are promising as described in some case reports. Bisphosphonates
showed good control in local recurrence. In vitro studies with Zolendronate
loaded bone cement and phase 2 trials of Denosumab showed hopeful results, may be
useful in future.
PMID- 28413542
TI - Lateral ventricular gliosarcoma with attachment to septum pellucidum.
AB - Gliosarcomas are lesions with both glial and sarcomatous elements and are usually
seen abutting the dura. Intraventricular location is extremely rare. Such an
unusual intraventricular gliosarcoma is being reported.
PMID- 28413543
TI - Primary intracranial choriocarcinoma presenting as a ring-enhancing lesion: A
case report and review of literature.
AB - We report here a rare case of primary intracranial choriocarcinoma without
evidence of tumor elsewhere, presenting as a ring-enhancing lesion managed
successfully in our institute (Grant Medical College and Sir J. J. Group of
Hospitals, Mumbai, Maharashtra, India). A 22-year-old, right-handed housewife
presented with complaints of headache, vomiting, generalized tonic-clonic
seizures, and right upper limb weakness of short duration. On neurological
examination, the patient was conscious, cooperative, well-oriented in time,
place, and person. Visual acuity was 6/9 in both eyes. Fundus was showing grade 1
papilledema. Tone was increased on the right side. Power was decreased in the
right upper limb as compared to the left. Reflexes were brisk in the right upper
limb. Imaging was suggestive of a thick ring-enhancing lesion in the left
parietal region suggestive of glioma or tuberculosis. Complete excision of the
lesion was achieved. The diagnosis was confirmed by histopathologic examination
of the lesion and beta-human chorionic gonadotropin (beta-HCG) levels. The
patient recovered well postoperatively without neurological deficit. She was
relieved of headache completely and there were no further episodes of vomiting or
seizures. The right upper limb weakness improved to 4+/5. Choriocarcinoma is the
most malignant lesion of all the gestational trophoblastic diseases. Primary
brain choriocarcinoma presenting as a ring-enhancing lesion has not been reported
in the literature. This diagnosis should be kept in mind, especially in young
females of child-bearing age group. Complete surgical excision with adjunctive
treatment is required to achieve prolonged remissions.
PMID- 28413544
TI - Abdominal schwannoma in a case of neurofibromatosis type 2: A report of a rare
combination.
AB - Neurofibromatosis-2 (NF2) is an autosomal-dominant disease, which is
characterized by vestibular schwannomas (VSs) (acoustic neurinoma) as well as
tumours of the peripheral and central nervous system, demonstrating a variety of
expression. A 12-year-old girl presented to us with headache and ataxia for four
months. We examined and found a lump in the right side of her abdomen. On
magnetic resonance imaging (MRI) of brain, a bilateral VS at the cerebellopontine
(CP) angle was detected, and on computerized tomography (CT) scan and
ultrasonography of her abdomen a large retroperitoneal schwannoma was revealed in
the right side of her abdomen. At first, the right-sided CP angle tumour and two
months later, the left-sided lesion was operated. After some days, she became
mute and incontinent, and was found to have hydrocephalus on CT scan. We
introduced a ventriculoperitoneal shunt. Then we operated the abdominal lump,
which was histologically proven as schwannoma. The association of these three
tumours is rare and untiring surgical approaches made her better. The patient
recovered well except bilateral mild facial and vestibulocochlear deficit.
PMID- 28413545
TI - Bilateral cervico-dorsal gossypiboma presenting as discharging sinus.
AB - Retained surgical sponge is an uncommon complication after laminectomy. A 67-year
old male presented with a discharging sinus in the cervical region following
cervical laminectomy. Magnetic resonance imaging (MRI) revealed bilateral
symmetrical lesions in the paraspinal area. Re-exploration revealed gauze pieces
on either side under the muscle. Persistent discharging wound after surgery
should arouse the possibility of a foreign body. Because of the rarity of
bilateral lesions, the present case is being reported.
PMID- 28413546
TI - Solitary plasmacytoma of temporal bone: A rare case report.
AB - Solitary plasmacytoma of base of skull is a rare disease. It presents with
headache, swelling, and other vague symptoms. Systemic work-up to rule out
multiple myeloma is necessary. Radiotherapy is the treatment of choice. We, here,
present a case of solitary plasmacytoma of base of skull in right temporal bone
in a 50-year-old female treated with surgery and radiotherapy.
PMID- 28413547
TI - Supratentorial intermediate grade meningeal melanocytoma with intratumoral bleed
in the background of neurocutaneous melanosis: Report of an unusual case and
review of literature.
AB - Primary melanocytic tumours of the central nervous system (CNS) are rare.
According to the WHO classification (2007), these tumours include diffuse
leptomeningeal melanosis, melanomatosis, melanocytoma, and primary CNS melanoma.
Meningeal melanocytoma, most commonly seen in the infratentorial compartment and
cervical spinal cord, is a benign primary melanocytic neoplasm. Primary CNS
melanoma, on the other hand, represents the malignant end of the spectrum.
Intermediate grade melanocytoma is a rare histological subtype of primary
meningeal tumours and is characterised by the clinicopathological features
between the two extremes. Neurocutaneous melanosis (NCM) is a rare phacomatosis
characterised by melanotic lesions on the skin and leptomeninges. Leptomeningeal
manifestation in NCM may be observed either in the form of diffuse leptomeningeal
melanosis or primary CNS melanoma. Melanocytomas are focal lesions and their
association with NCM is extremely rare. In this report, we present an unusual
case of NCM accompanied by right frontal intermediate grade melanocytoma with
intratumoral bleeding in a 17-year-old boy. A brief literature review is also
presented.
PMID- 28413548
TI - An interesting case of wrongly diagnosed optic neuritis.
AB - Optic neuritis (ON) may rarely mimic optic nerve tumor, index of suspicion should
be kept high. A 34-year-old woman presented to a major academic institute with a
history of right-sided ocular pain and progressive visual loss in the same eye.
Her magnetic resonance imaging showed markedly thickened optic nerve; her workup
for inflammatory pathology was negative; she was diagnosed as a case of optic
nerve tumor and was planned for surgery. Patient for second opinion came to a
tertiary care institute where on proper history taking and evaluation she was
diagnosed and treated on the lines of ON and she improved. The diagnosis of ON is
a clinical one, it may mimic optic nerve tumor in rare cases.
PMID- 28413549
TI - Challenges in a case of ophthalmic artery aneurysm associated with abnormal
internal carotid arteries.
AB - Ophthalmic artery aneurysms account for 5% of all cerebral aneurysms and are an
important cause of morbidity and mortality related to subarachnoid hemorrhage.
The diagnosis is often made only when the aneurysm is large enough to become
symptomatic. They remain technically challenging for both neurosurgeon and
interventional radiologist. We present the case of a 62-year-old woman admitted
for transient loss of consciousness, followed by generalized tonic-clonic
seizures. Computed tomography (CT) showed a subarachnoid hemorrhage (SAH),
clinically graded as Hunt and Hess III. Magnetic resonance imaging (angioMR) and
the four-vessel digital subtraction angiography (DSA) identified a ruptured, 8 mm
left ophthalmic artery aneurysm. Embolization was the first therapeutic choice.
Nevertheless, the attempt had to be aborted due to a combination of a hypoplastic
right internal carotid artery (ICA) and an irregular atheromatous plaque on the
left ICA, rendering the procedure unduly hazardous. Therefore, microsurgical
clipping of the aneurysm became the procedure of choice. Postoperatively, the
patient was in good condition, with no visual and neurological deficits. At 6
months follow up, she was assigned maximum scores of 5 and 8 on the Glasgow
Outcome Scale (GOS) and Extended GOS (GOS-E), respectively. Aneurysm rupture
represents a neurosurgical emergency and an early intervention (less than 48 h)
is recommended to maximize the chances of deficit-free survival. The
peculiarities of this case consisted in the combination between the size and the
location of the aneurysm, abrupt presentation, and the impossibility of
embolization due to bilateral ICA abnormalities, congenital (hypoplastic right
ICA) and acquired (extensively atherosclerotic left ICA).
PMID- 28413550
TI - Primary intracranial rhabdomyosarcoma of the cerebellopontine angle mimicking a
vestibular schwannoma in a child.
AB - Primary intracranial rhabdomyosarcoma (PIRMS) is a rare neoplasm, which affects
infants and young children. We report a rare case of a primary embryonal
rhabdomyosarcoma of the cerebellopontine angle in a 7-year-old boy with clinical
and radiological features mimicking a vestibular schwannoma. The patient
underwent definitive surgery and radiotherapy and is recurrence free at 6 months.
PIRMS commonly occur in parameningeal locations or metastasize to the brain from
an extracranial primary. Gross total tumor resection followed by adjuvant
radiotherapy remains the current standard of treatment; however, chemotherapy has
also been tried with favorable results. The overall prognosis continues to remain
poor.
PMID- 28413551
TI - Alveolar soft part sarcoma with brain metastases.
AB - Metastatic tumors are the most common mass lesions in the brain. This case
reports a rare form of sarcoma with metastasis to the brain. The appropriate
management of a patient with metastatic alveolar soft part sarcoma to the brain
is discussed. Author describes a 32-year-old gentleman diagnosed with primary
tumor at gluteus and distant metastases at lower lobe of right lung and the
brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy
with excision of brain lesion was done. Repeated magnetic resonance imaging of
the brain after 2 months showed rapidly growing new lesions. The next step of
management was made by the oncology team as recurrence rate was high and due to
multi-systemic involvement. Patient was planned for palliative chemotherapy and
to be reassessed later. This case report discusses the appropriate approach to
any form of brain metastases and the role of early follow-up especially after
surgery for better outcome and choice of post operative management such as
radiotherapy or chemotherapy or both for malignant tumors. Based on this report,
it was concluded that every brain tumor patient should be frequently monitored
even in the outpatient setting as most of them are metastatic and rapidly
spreading. The patient should be considered for radiotherapy or chemotherapy or
both after surgery if the histopathology result is suggestive of malignancy.
PMID- 28413552
TI - Trigeminocardiac reflex preceding development of postoperative superior orbital
fissure syndrome.
AB - The superior orbital fissure syndrome (SOFS) is a rare condition presenting as
painful unilateral opthalmoplegia, ptosis, pupillary dilatation and anesthesia of
the upper eyelid and forehead. It has been described after facial trauma. Other
etiologies include infections, tumors or spontaneous hemorrhages in the retro
orbital space. Occurrence of SOFS after surgery in the skull base has not been
described before. We recently encountered a case where a young female developed
SOFS following surgery for cerebrospinal fluid (CSF) rhinorrhea. The occurrence
of SOFS was preceded by episodes of trigemino-cardiac reflex (TCR) during the
surgery. This is the first case report associating TCR with SOFS. We managed the
case report with megadose methylprednisolone and the patient showed improvement
in the deficit over time.
PMID- 28413553
TI - Excision of hypoglossal neurinoma by condyle sparing suboccipital keyhole
approach.
AB - Hypoglossal neurinomas are rare tumors that present with gradually worsening
unilateral wasting of the tongue. The tumors often attain large size prior to
detection and often extend into the hypoglossal canal. Large tumors can distort
the brainstem and cerebellum. Preoperative diagnosis can often be made by
magnetic resonance imaging (MRI) with contrast enhancement. Traditionally,
surgery for these tumors has entailed large transcondylar approaches, often
necessitating occipitocervical stabilization. We managed one 23-year-old female
patient with a large hypoglossal neurinoma. The tumor could be excised completely
by a condyle-sparing minimally invasive suboccipital keyhole approach.
PMID- 28413554
TI - Confounding features of ectopic craniopharyngioma: A differential for tumors
showing diffusion restriction.
AB - Craniopharyngiomas comprise approximately 1-3% of all intracranial tumors and
arise from squamous epithelial rests along remnants of Rathke's cleft. They have
bimodal age distribution. The ectopic sites reported are the nasopharynx,
sphenoid bone, pineal region, cerebellopontine angle and third ventricle. We
report a case of ectopic craniopharyngioma in the Foramen of Monro with
restricted diffusion, which have is an unusual feature, not commonly reported and
is a potential pitfall.
PMID- 28413555
TI - Dissecting intracranial aneurysm in pregnancy: A rare association.
AB - We report a case of dissecting aneurysm of the right posterior cerebral artery
presenting with sudden onset headache and altered behavior during labor. A 26
year-old P1001 with uncomplicated antenatal period, except history of headache
off and on since 32 weeks of pregnancy, developed sudden onset headache and
altered behavior during 3rd stage of labor. She had vaginal delivery and a live
born male baby was delivered with good Apgar score. The CT was suggestive of
subarachnoid hemorrhage and DSA was suggestive of dissecting aneurysm of the
right P2 segment with hypoplasia of right P1 segment and A1 segment of posterior
and anterior cerebral artery, respectively. The patient was managed
conservatively. At 4-month follow-up, the patient was doing well. We discuss
about the rare association of a dissecting aneurysm and pregnancy, especially
dissection of the posterior cerebral artery.
PMID- 28413556
TI - Totally cystic intradural schwannoma in thoracic region.
AB - Spinal schwannomas are benign intradural extramedullary tumors arising from
spinal nerve root sheath. They are usually solid or heterogeneously solid.
Totally cystic schwannomas are rare entities. Herein, we report a 60-year-old
male presenting with backache radiating along the chest wall and weakness of both
lower limbs. He had spastic paraparesis. Magnetic resonance imaging revealed a
cystic mass in the thoracic region. At operation, the cystic mass was seen to be
attached to D4 dorsal rootlets. It was excised in toto and histopathology
confirmed it to be a schwannoma. The relevant literature is reviewed.
PMID- 28413557
TI - C2 Primary leiomyoma in an immunocompetent woman: A case report and review of
literature.
AB - Clinical case report and review of the literature. This is the first case of
primary leiomyoma in an immunocompetent woman without previous history of uterine
leiomyoma being reported in the literature to the best of our knowledge.
Leiomyoma, a type of smooth muscle cell tumor, involving the vertebra is
extremely rare. There were very few primary leiomyoma in patients with AIDS or in
the immune-suppressed patients. This 48-year-old female came with H/o neck pain,
weakness and bladder retention. On examination, tone increased in all four limbs,
power on the right side of the limbs 4/5, power on the left upper limb 0/5, lower
limb 3/5, left plantar was up going, decreased sensation over the left second
cervical vertebra (C2) dermatome and all modalities decreased below C2. X-ray and
magnetic resonance imaging (MRI) of the cervical spine showed kyphosis of the
cervical spine with destruction of the C2 vertebral body along with pathological
fracture. The patient underwent decompression of the C2 lesion through the C2
right pedicle with occipito-C1-C3 lateral mass screws fixation. Lesion anterior
to the cord was reached by a transpedicular approach and decompression was
performed. The lesion was pinkish grey, firm and moderately vascular and was
destroying the C2 vertebral body. The patient improved symptomatically in power
in the left upper limb and lower limb over the next 1 week duration from 0/5 to
4+/5. Histopathology revealed primary leiomyoma. The patient was evaluated with
ultrasound abdomen and contrast tomogram of the chest, abdomen and pelvis to rule
out other possible lesions in the lung, intestines and uterus. We suggest that
leiomyoma should be included in the differential diagnosis of destructive lytic
lesions involving the C2 vertebra. Histopathological examination with
immunohistochemistry is necessary for the definitive diagnosis. Treatment of
choice is surgery with complete removal.
PMID- 28413558
TI - Choroid plexus papilloma.
AB - Choroid plexus tumors are rare intracranial tumors which account for only 0.4
0.6% of all brain tumors. These are intraventricular papillary neoplasms derived
from choroid plexus epithelium and range from choroid plexus papillomas (World
Health Organisation (WHO) grade I) to choroid plexus carcinomas (WHO grade III).
It is an important albeit rare cause of hydrocephalous. We present to you the
case of a 1-year-old child who presented with the signs and symptoms of
hydrocephalous and was diagnosed as choroid plexus papilloma on histopathology.
PMID- 28413559
TI - Intracranial hemorrhage from giant aneurysm in pregnancy: A rare association.
AB - We report a case of giant aneurysm causing subarachnoid hemorrhage in a pregnant
female. A 25-year-old female presented with sudden onset of severe headache and
vomiting with altered sensorium and right hemiplegia. On investigation, she had a
giant supraclinoid segment internal carotid artery (ICA) aneurysm. She was
planned for digital substraction angiography, but during the procedure she
deteriorated neurologically and went into spontaneous labor. The baby was a male
child with weight of 1.1 kg. She was taken up for surgery and aneurysm was
clipped. We discuss the rare occurrence of intracranial hemorrhage in pregnancy
due to a giant ICA aneurysm.
PMID- 28413560
TI - Occipital condyle syndrome as the first sign of skull metastasis from lung
cancer.
PMID- 28413561
TI - Economic and outcome following severe head injury.
PMID- 28413562
TI - Pneumocephalus is not a serious outcome after surgery for chronic SDH.
PMID- 28413563
TI - Severe hypotension in transforaminal lumbar interbody fusion surgery: Is it
vasovagal or?
PMID- 28413564
TI - Extensive traumatic thalamic contusions in a child.
PMID- 28413565
TI - Enrichment of in vivo transcription data from dietary intervention studies with
in vitro data provides improved insight into gene regulation mechanisms in the
intestinal mucosa.
AB - BACKGROUND: Gene expression profiles of intestinal mucosa of chickens and pigs
fed over long-term periods (days/weeks) with a diet rich in rye and a diet
supplemented with zinc, respectively, or of chickens after a one-day amoxicillin
treatment of chickens, were recorded recently. Such dietary interventions are
frequently used to modulate animal performance or therapeutically for monogastric
livestock. In this study, changes in gene expression induced by these three
interventions in cultured "Intestinal Porcine Epithelial Cells" (IPEC-J2)
recorded after a short-term period of 2 and 6 hours, were compared to the in vivo
gene expression profiles in order to evaluate the capability of this in vitro
bioassay in predicting in vivo responses. METHODS: Lists of response genes were
analysed with bioinformatics programs to identify common biological pathways
induced in vivo as well as in vitro. Furthermore, overlapping genes and pathways
were evaluated for possible involvement in the biological processes induced in
vivo by datamining and consulting literature. RESULTS: For all three
interventions, only a limited number of identical genes and a few common
biological processes/pathways were found to be affected by the respective
interventions. However, several enterocyte-specific regulatory and secreted
effector proteins that responded in vitro could be related to processes regulated
in vivo, i.e. processes related to mineral absorption, (epithelial) cell
adherence and tight junction formation for zinc, microtubule and cytoskeleton
integrity for amoxicillin, and cell-cycle progression and mucus production for
rye. CONCLUSIONS: Short-term gene expression responses to dietary interventions
as measured in the in vitro bioassay have a low predictability for long-term
responses as measured in the intestinal mucosa in vivo. The short-term responses
of a set regulatory and effector genes, as measured in this bioassay, however,
provided additional insight into how specific processes in piglets and broilers
may be modulated by "early" signalling molecules produced by enterocytes. The
relevance of this set of regulatory/effector genes and cognate biological
processes for zinc deficiency and supplementation, gluten allergy (rye), and
amoxicillin administration in humans is discussed.
PMID- 28413566
TI - A Hierarchical Predictive Coding Model of Object Recognition in Natural Images.
AB - Predictive coding has been proposed as a model of the hierarchical perceptual
inference process performed in the cortex. However, results demonstrating that
predictive coding is capable of performing the complex inference required to
recognise objects in natural images have not previously been presented. This
article proposes a hierarchical neural network based on predictive coding for
performing visual object recognition. This network is applied to the tasks of
categorising hand-written digits, identifying faces, and locating cars in images
of street scenes. It is shown that image recognition can be performed with
tolerance to position, illumination, size, partial occlusion, and within-category
variation. The current results, therefore, provide the first practical
demonstration that predictive coding (at least the particular implementation of
predictive coding used here; the PC/BC-DIM algorithm) is capable of performing
accurate visual object recognition.
PMID- 28413567
TI - Differential adipokine DNA methylation and gene expression in subcutaneous
adipose tissue from adult offspring of women with diabetes in pregnancy.
AB - BACKGROUND: Offspring of women with diabetes in pregnancy are at increased risk
of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic
mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ,
RETN) play key roles in the pathophysiology of T2DM. We hypothesized that
offspring exposed to maternal diabetes exhibit alterations in epigenetic
regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We
studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP,
ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N
= 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of
women from the background population (O-BP, N = 57). RESULTS: Compared to O-BP,
we found elevated plasma leptin and resistin levels in O-T1DM, decreased gene
expression of all adipokines in O-GDM, decreased RETN expression in O-T1DM, and
increased LEP and ADIPOQ methylation in O-GDM. In multivariate regression
analysis, O-GDM remained associated with increased ADIPOQ methylation and
decreased ADIPOQ and RETN gene expression and O-T1DM remained associated with
decreased RETN expression after adjustment for potential confounders and
mediators. CONCLUSIONS: In conclusion, offspring of women with diabetes in
pregnancy exhibit increased ADIPOQ DNA methylation and decreased ADIPOQ and RETN
gene expression in SAT. However, altered methylation and expression levels were
not reflected in plasma protein levels, and the functional implications of these
findings remain uncertain.
PMID- 28413568
TI - Triphenylamine-Based Push-Pull Molecule for Photovoltaic Applications: From
Synthesis to Ultrafast Device Photophysics.
AB - Small push-pull molecules attract much attention as prospective donor materials
for organic solar cells (OSCs). By chemical engineering, it is possible to
combine a number of attractive properties such as broad absorption, efficient
charge separation, and vacuum and solution processabilities in a single molecule.
Here we report the synthesis and early time photophysics of such a molecule, TPA
2T-DCV-Me, based on the triphenylamine (TPA) donor core and dicyanovinyl (DCV)
acceptor end group connected by a thiophene bridge. Using time-resolved
photoinduced absorption and photoluminescence, we demonstrate that in blends with
[70]PCBM the molecule works both as an electron donor and hole acceptor, thereby
allowing for two independent channels of charge generation. The charge-generation
process is followed by the recombination of interfacial charge transfer states
that takes place on the subnanosecond time scale as revealed by time-resolved
photoluminescence and nongeminate recombination as follows from the OSC
performance. Our findings demonstrate the potential of TPA-DCV-based molecules as
donor materials for both solution-processed and vacuum-deposited OSCs.
PMID- 28413569
TI - Adsorption and Dissociation of CO2 on Ru(0001).
AB - The adsorption and dissociation of carbon dioxide on a Ru(0001) single crystal
surface was investigated by reflection-absorption infrared spectroscopy (RAIRS)
and temperature-programmed desorption (TPD) spectroscopy for CO2 adsorbed at 85
K. RAIRS spectroscopy shows that the adsorption of CO2 on a Ru(0001) single
crystal is partially dissociative, resulting in CO2 and CO. The CO vibrational
mode was also observed to split into two distinct modes, indicating two general
populations of CO present at the surface. Furthermore, a time-dependent blue
shift is observed, which is characteristic of increasing CO surface coverage. TPD
showed that coverages of up to 0.3 ML were obtained, and no evidence for
chemisorption of oxygen on ruthenium was found.
PMID- 28413570
TI - Role of Adsorbed Water on Charge Carrier Dynamics in Photoexcited TiO2.
AB - Overall photocatalytic water splitting is one of the most sought after processes
for sustainable solar-to-chemical energy conversion. The efficiency of this
process strongly depends on charge carrier recombination and interaction with
surface adsorbates at different time scales. Here, we investigated how hydration
of TiO2 P25 affects dynamics of photogenerated electrons at the millisecond to
minute time scale characteristic for chemical reactions. We used rapid scan
diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS). The decay
of photogenerated electron absorption was substantially slower in the presence of
associated water. For hydrated samples, the charge carrier recombination rates
followed an Arrhenius-type behavior in the temperature range of 273-423 K; these
became temperature-independent when the material was dehydrated at temperatures
above 423 K or cooled below 273 K. A DFT+U analysis revealed that hydrogen
bonding with adsorbed water stabilizes surface-trapped holes at anatase TiO2(101)
facet and lowers the barriers for hole migration. Hence, hole mobility should be
higher in the hydrated material than in the dehydrated system. This demonstrates
that adsorbed associated water can efficiently stabilize photogenerated charge
carriers in nanocrystalline TiO2 and suppress their recombination at the time
scale up to minutes.
PMID- 28413572
TI - Guest Editor Dale Hamilton Provides Expert Guidance for Special Issue on Cardiac
Metabolism.
PMID- 28413573
TI - Journal Announces New Changes for 2017.
PMID- 28413571
TI - Asthma control in primary care: the results of an observational cross-sectional
study in Italy and Spain.
AB - BACKGROUND: Poor asthma control observed in several surveys may be related to a
lack of systematic assessment by physicians and/or to patient underestimation of
symptoms. Along this line, the purpose of this study was to investigate the level
of asthma control in patients attending the GP office for different reasons,
either for renewal of drug prescription or for worsening of asthma symptoms.
METHODS: Each of the 145 General Practitioners (GP) in Italy and Spain selected
at least eight asthmatic patients attending their office for a renewal of drug
prescription (Group A) or for worsening of asthma symptoms (Group B), between May
and December 2009. Asthma Control Test (ACT) and other clinical information
(including SF-12 questionnaire) were collected. RESULTS: Data from 1375 patients
with moderate-severe asthma were analysed (mean age: 47.2 years; female: 59%;
smokers or ex-smokers: 35.4%); 57% were on treatment with ICS-LABA combination.
ACT score < 20 (uncontrolled asthma) was observed in 77.8% Group B patients, as
expected, but also in 28.6% Group A patients. Uncontrolled patients reported
their asthma being well or fairly well controlled in 68.4% of cases. Risk factors
for uncontrolled asthma were older age, asthma severity, and smoking habit. In
uncontrolled patients, GPs changed or increased the level of therapy in 75.8% and
initiated asthma treatment in 61.3% of cases, in association with educational
intervention, closer monitoring or pulmonologist consultations. DISCUSSION: The
systematic use of ACT in asthmatics attending GP's clinic may detect high rates
of uncontrolled patients who underestimate their clinical conditions,
particularly those asking solely for asthma medication renewal. Poor adherence to
daily drug therapy was reported in more than 40% of patients and could be an
important contributor of uncontrolled asthma. CONCLUSIONS: The results highlight
the importance of routine longitudinal assessment of asthma patients in primary
care and point to the need for an increased attention to asthma management by
GPs.
PMID- 28413574
TI - The Failing Heart: Energy Supply, Processing, and Transfer.
PMID- 28413575
TI - The Role of Estrogen in Cardiac Metabolism and Diastolic Function.
AB - Heart failure with preserved ejection fraction (HFpEF) has similar prevalence and
prognosis as HF with reduced EF, but there is no approved treatment for HFpEF.
HFpEF is common in postmenopausal women, which suggests that the absence of
estrogen (E2) plays a role in its pathophysiology. With the country's growing
elderly population, the prevalence of HFpEF is rapidly increasing. This has
triggered a renewed urgency in finding novel approaches to preventing and slowing
the progression of HFpEF. In this review, we address the role of E2 in left
ventricular diastolic function and how it impacts women with HFpEF as well as
animal models. We also discuss the primary potential mechanisms that represent
critical nodes in the mechanistic pathways of HFpEF and how new treatments could
be developed to target those mechanisms.
PMID- 28413576
TI - Timing and Targeting of Treatment in Left Ventricular Hypertrophy.
AB - In most clinical cases, left ventricular hypertrophy (LVH) occurs over time from
persistent cardiac stress. At the molecular level, this results in both transient
and long-term changes to metabolic, sarcomeric, ion handling, and stress
signaling pathways. Although this is initially an adaptive change, the mechanisms
underlying LVH eventually lead to maladaptive changes including fibrosis,
decreased cardiac function, and failure. Understanding the regulators of long
term changes, which are largely driven by transcriptional remodeling, is a
crucial step in identifying novel therapeutic targets for preventing the
downstream negative effects of LVH and treatments that could reverse or prevent
it. The development of effective therapeutics, however, will require a critical
understanding of what to target, how to modify important pathways, and how to
identify the stage of pathology in which a specific treatment should be used.
PMID- 28413577
TI - Circadian Control of Cardiac Metabolism: Physiologic Roles and Pathologic
Implications.
AB - Over the course of the day, the heart is challenged with dramatic fluctuations in
energetic demand and nutrient availability. It is therefore not surprising that
rhythms in cardiac metabolism have been reported at multiple levels, including
the utilization of glucose, fatty acids, and amino acids. Evidence has emerged
suggesting that the cardiomyocyte circadian clock is in large part responsible
for governing cardiac metabolic rhythms. In doing so, the cardiomyocyte clock
temporally partitions ATP generation for increased contractile function during
the active period, promotes nutrient storage at the end of the active period, and
facilitates protein turnover (synthesis and degradation) during the beginning of
the sleep phase. This review highlights the roles of cardiac metabolism rhythms
as well as the potential pathological consequences of their impairment.
PMID- 28413578
TI - Epicardial Fat in the Maintenance of Cardiovascular Health.
AB - Epicardial fat is a unique adipose tissue located between the myocardium and the
visceral layer of pericardium. This tissue is characterized by highly active
fatty acid metabolism and highly expressed thermogenic genes. Epicardial fat and
the underlying myocardium share the same microcirculation, suggesting a close and
strong interaction between these two structures. Under physiological conditions,
epicardial fat protects and supports the heart to exert its normal function. Many
clinical studies have shown significant associations between increased amounts of
epicardial fat and coronary artery disease (CAD). In patients with CAD, increased
epicardial fat becomes inflammatory and may promote plaque development through
secretion of proinflammatory cytokines and other mechanisms. Therefore,
epicardial fat is a biomarker of cardiovascular risk and a potential therapeutic
target for cardiovascular disease. Weight loss and pharmaceuticals can reduce
epicardial fat and improve its protective physiological functions.
PMID- 28413579
TI - Metabolic Recovery of the Failing Heart: Emerging Therapeutic Options.
AB - Heart failure has mortality rates that parallel those of breast cancer. Current
management strategies include neurohormonal blockade, rate control measures,
natriuretic peptide preservation, implantation of mechanical assist devices, and
heart transplantation. Despite these strategies, however, the failing myocardium
remains energy depleted. New strategies to promote metabolic recovery are being
developed to potentially augment current treatment guidelines. For example, an
unexpected finding of our own studies showed that mechanical unloading with
assist devices in advanced-stage heart failure restored metabolic flux.
Unfortunately, at that point it is too late for myocardial recovery. Traditional
metabolic therapies addressing hyperglycemia have had limited long-term outcome
benefit. Now, new therapeutic options are emerging based on increased
understanding of the molecular mechanisms underlying energy depletion. Metabolic
cardiac imaging combined with laboratory diagnostics could guide the design of
individual therapeutic strategies. To date, agents that show benefit in select
individuals include mimetics that stimulate glucagon-like peptide-1, inhibitors
of sodium-glucose cotransporter receptors, drugs that limit fatty acid oxidation,
and hormonal therapy in select individuals. This review will summarize mechanisms
and investigations related to these metabolic approaches to heart failure.
PMID- 28413580
TI - Pet Imaging and its Application in Cardiovascular Diseases.
AB - Cardiovascular diseases (CVDs) are the leading cause of death worldwide and
represent a great challenge for modern research and medicine. Despite advances in
preventing and treating CVD over the decades, there remains an urgent need to
develop sensitive and safe methods for early detection and personalized
treatment. With refinements of molecular imaging technologies such as positron
emission tomography (PET), noninvasive imaging of CVDs is experiencing impressive
progress in both preclinical and clinical settings. In this review, we summarize
advances in cardiovascular PET imaging, highlight the latest development of CVD
imaging probes, and illustrate the potential for individualized therapy based on
metabolic phenotype.
PMID- 28413583
TI - Cardiac Metastases in a Patient with Advanced Squamous Cell Carcinoma of the
Lung.
PMID- 28413581
TI - Robotic-Assisted Inferior Vena Cava Filter Retrieval.
AB - Although anticoagulation remains the mainstay of therapy for patients with venous
thromboembolism, guidelines recommend the use of inferior vena cava (IVC) filters
in those who fail anticoagulation or have contraindications to its use. Short
term use of filters has proven effective in reducing the rate of pulmonary
embolism. However, their extended use is associated with a variety of
complications such as thrombosis, filter migration, or caval perforation, thus
making a case for timely filter retrieval. This is the case of a 68-year-old
female with a history of chronic oral anticoagulation use for multiple deep
venous thrombi (DVT) and pulmonary emboli (PE) who required cervical and thoracic
spinal intervention for spondylosis and foramina stenosis. Given her increased
risk of recurrent DVT and PE perioperatively, we elected to place a Cook CelectTM
IVC filter (Cook Medical, Bloomington, IN) after oral anticoagulation was stopped
for the procedure. Her treatment course was prolonged due to wound-healing
complications. We elected to use the Magellan Robotic Catheter System (Hansen
Medical, Mountain View, CA) for filter retrieval when she presented 6 months
later with caval perforation from the filter struts. With its ease of use,
superior mechanical stability, and maneuverability, robot-assisted IVC filter
retrieval may be a safer and more reliable substitute for traditional navigation
techniques when presented with challenging filter retrievals.
PMID- 28413582
TI - A Case of Iatrogenic Aortic Intramural Hematoma.
AB - Iatrogenic aortic dissection during percutaneous coronary intervention is a rare
but serious complication. Both conservative and surgical approaches have been
proposed as management strategies. We describe a case of an 87-year-old female
who presented with an acute coronary syndrome complicated by the development of
an ascending aortic dissection during percutaneous intervention, and we provide a
brief review of the literature.
PMID- 28413585
TI - Pied Beauty.
PMID- 28413584
TI - Hyponatremia in Heart Failure.
PMID- 28413587
TI - Arctic Blimp and Sub on Ray.
PMID- 28413586
TI - The Methodist DeBakey Heart & Vascular Center a Poetic History (Abridged).
PMID- 28413588
TI - Relative biocompatibility of micro-hybrid and nano-hybrid light-activated
composite resins.
AB - Background. In vitro studies have revealed a direct association between resin
content and cytotoxicity of composite resins; however, implantation studies in
this regard are sparse. This study investigates the relationship between filler
content of composite resins and biocompatibility. Methods. This research employed
twelve 180-200-gr male Wistar rats, 1 nano-hybrid (Prime-Dent Inc.) and 1 micro
hybrid (Medental Inc.) composite resins containing 74% and 80-90% filler content,
respectively. The samples were assessed on the 2nd, 14th and 90th day of
implantation. Four rats were allocated to each day in this experimental study. A
section of 1.5mm long cured nano-hybrid and micro-hybrid materials were implanted
into the right and left upper and lower limbs of the rats, respectively. Eight
samples were generated on each day of observation. Inflammation was graded
according to the criteria suggested by Orstavik and Major. Pearson's chi-squared
test was employed to determine the relationship between the tissue responses of
the two materials. Statistical significance was set at P < 0.05. Results . The
average grade of inflammation for the nano-hybrid on the 2nd day of implantation
was 3.3. The micro-hybrid resin had a score of 3.0 for cellular inflammation. On
the 14th day, the micro-hybrid resin also exhibited a lower average grade for
cellular inflammation. On the 90th day, the micro-hybrid resin had a higher grade
of inflammation (0.9) compared to 0.3 recorded for nano-hybrid. The composite
resins with higher filler content elicited a significantly lower grade of
inflammation irrespective of the duration (chi=20.000, df=8, P=0.010) while the
composite resins with lower filler content elicited a significantly lower
inflammatory response on the 90th day (chi=4.000, df=1, P=0.046). Conclusion. The
composite resins with higher filler content generally elicited significantly
lower grades of inflammation, and the composite resins with lower filler content
exhibited significantly lower inflammatory response on the 90th day of
implantation.
PMID- 28413589
TI - The color masking ability of a zirconia ceramic on the substrates with different
values.
AB - Background. The color masking ability of a restoration plays a significant role
in coveringa discolored substructure; however, this optical property of zirconia
ceramics has not been clearly determined yet. The aim of this in vitro study was
to evaluate the color masking ability of a zirconia ceramic on substrates with
different values. Methods. Ten zirconia disk specimens,0.5 mm in thickness and 10
mm in diameter, were fabricated by a CAD/CAM system. Four substrates with
different values were prepared, including: white (control), light grey, dark
grey, and black. The disk specimens were placed over the substratesfor
spectrophotometric measurements. A spectrophotometer measured the L*, a*, and b*
color attributes of the specimens. Additionally, DeltaE values were calculated to
determine the color differences between each group and the control,and were then
compared with the perceptional threshold of DeltaE=2.6. Repeated-measures ANOVA,
Bonferroni, and one-sample t-test were used to analyze data. All the tests were
carried out at 0.05 level of significance. Results. The means and standard
deviations of DeltaE values for the three groups of light grey, dark grey and
black were 9.94+/-2.11, 10.40+/-2.09, and 13.34+/-1.77 units,
respectively.Significant differences were detected between the groups in the
DeltaE values (P<0.0001).The DeltaE values in all the groups were more than the
predetermined perceptional threshold(DeltaE>2.6) (P<0.0001). Conclusion. Within
the limitations of this study, it was concluded that the tested zirconia ceramic
did not exhibit sufficient color masking ability to hide the grey and black
substrates.
PMID- 28413590
TI - Effect of nano-hydroxyapatite toothpaste on microhardness ofartificial carious
lesions created on extracted teeth.
AB - Background. Many types of toothpastes contain substances that can remineralize
initial enamel caries. This study aimed to assess the effect of nano
hydroxyapatite (NHA) on microhardness of artificially created carious lesions.
Methods. In this in vitro study, NHA was prepared using sol-gel technique and
added to the toothpaste with 7% concentration. A total of 80 extracted sound
teeth were collected. The crowns were polished using 500-grit abrasive paper. The
specimens were randomly coded from 1 to 80. Number 1 to 40 were assigned to group
A and numbers 41 to 80 to group B. The microhardness was measured using HVS-1000
Vickers microhardness tester. The specimens were demineralized using 37%
phosphoric acid for 3 minutes in order to create artificial carious lesions and
then were rinsed with water, air-sprayed for 3 minutes and dried. Microhardness
was measured again. Next, the specimens were brushed for 15 days, twice daily,
for 15 seconds. After 15 days, microhardness was measured again. Toothpaste A
contained NHA and fluoride and toothpaste B contained fluoride alone. Data were
analyzed using SPSS 16, with one-sample Kolmogorov-Smirnov test and ANOVA at a
significance level of P<0.05. Results. The microhardness of specimens
significantly decreased following acid exposure (P<0.01) but increased again in
both groups after exposure to toothpastes. The increase in microhardness was
significantly greater in group A (P<0.01). Conclusion. The toothpaste containing
NHA was more effective than the toothpaste without NHA for the purpose of
remineralization.
PMID- 28413591
TI - Comparative evaluation of efficacy of subgingivally delivered 1.2% Atorvastatin
and 1.2% Simvastatin in the treatment of intrabony defects in chronic
periodontitis: a randomized controlled trial.
AB - Background. Statins are the recently evolved agents that aid in periodontal
regeneration and ultimately in attaining periodontal health. Atorvastatin (ATV)
and Simvastatin (SMV) are specific competitive inhibitors of 3-hydroxy-2-methyl
glutaryl coenzyme A reductase. The current study was conducted to compare the
effectiveness of 1.2% ATV and 1.2% SMV, in addition to scaling and root planing
(SRP), in the treatment of intrabony defects in subjects with chronic
periodontitis. Methods. Ninety-six individuals were categorized into three
treatment groups: SRP plus 1.2% ATV, SRP plus 1.2% SMV and SRP plus placebo.
Clinical parameters of full-mouth plaque index (PI), modified sulcus bleeding
index (mSBI), probing depth (PD), and relative attachment level (RAL) were
recorded at baseline before SRP and at 3, 6 and 9 months. Bone fill was assessed
using percentage radiographic defect depth reduction at baseline, 6 months and 9
months. Results. Both ATV and SMV showed significant PD reduction and RAL gain
than placebo. ATV group showed greater mean PD reduction and mean RAL gain as
compared to SMV group at 3, 6 and 9 months. Furthermore, ATV group sites
exhibited a significantly greater percentage of radiographic defect depth
reduction (33.23 +/- 3.11%; 34.84 +/- 3.07%) as compared to SMV (30.39 +/- 3.36%;
32.15 +/- 3.37%) at 6 and 9 months. Conclusion. ATV resulted in greater
improvements in clinical parameters with higher percentage of radiographic defect
depth reduction as compared to SMV in the treatment of intrabony defects in CP
subjects.
PMID- 28413592
TI - Marginal bone loss around platform-switched and non-platform switched implants
after two years of placement: a clinical trial.
AB - Background. The present study was conducted to investigate the marginal bone loss
around two different types of implant-abutment junctions, called platform
switched (Implantium system) and non-platform switched (XiVE system) after two
years of loading. Methods. Sixty-four implants in 49 patients were included in
the study. The implants were placed in the posterior mandibular region according
to the relevant protocols. The extent of bone loss around the implants was
measured and compared after 24 months, using digital parallel periapical
radiographs. Results. The means +/- SE of bone loss values in the platform
switched and non-platform-switched groups were 0.47 +/- 0.048 mm and 1.87 +/-
0.124 mm, respectively. The difference between the two groups was statistically
significant (P < 0.0001). Conclusion . The platform-switching technique seems to
reduce the periimplant crestal bone resorption, which supports the long-term
predictability of implant therapy.
PMID- 28413593
TI - Comparison of bracket bond strength to etched and unetched enamel under dry and
wet conditions using Fuji Ortho LC glass-ionomer.
AB - Background. Acid etching prior to orthodontic bracket bonding may result in
enamel wear or cracks following bracket removal. The manufacturer of Fuji Ortho
LC glass-ionomer (GI) claims that it can bond brackets to wet unetched enamel.
This study aimed to compare the bracket bond strength to etched and unetched
enamel under dry and wet conditions. Methods. In this in vitro study, 60 intact
premolar teeth were randomly assigned to 6 groups (etched and dried, etched and
moistened with distilled water, etched and moistened with saliva, unetched and
dried, unetched and moistened with water, unetched and moistened with saliva). In
all the groups, Leon 4 brackets were bonded to the enamel using Fuji Ortho LC GI.
The teeth were immersed in distilled water at 37 degrees C for 24 hours and
subjected to shear loads at a crosshead speed of 5 mm/min in a Zwick machine for
bond strength testing. Data were analyzed with ANOVA, Tukey test and independent
t-test. Results . The mean bond strength values in groups 1 (etched, dry), 2
(etched, moistened with water), 3 (etched, moistened with saliva), 4 (unetched,
dry), 5 (unetched, moistened with water) and 6 (unetched, moistened with saliva)
were 21.86, 16.46, 10.49, 8.12, 9.15 and 9.52 MPa, respectively. Significant
differences in bond strength were detected between groups 1 and 2 and all the
other groups (P < 0.05), with no significant difference between groups 1 and 2 (P
> 0.05). Conclusion. Fuji Ortho LC GI provided adequate bond strength between
brackets and enamel. To acquire higher bond strength, brackets must be bonded to
etched and dried enamel.
PMID- 28413595
TI - Effect of retreatment on the push-out bond strength of MTA-based and epoxy resin
based endodontic sealers.
AB - Background. Further studies on the adhesion properties of MTA-based materials
seem necessary due to their growing use in endodontic treatment. This research
aimed to assess the effect of retreatment on the bond strength of MTA-based (MTA
Fillapex) and epoxy resin-based (AH Plus) sealers. Methods. ProTaper rotary files
were applied to prepare the root canals of 80 human mandibular premolars. Then,
the roots were randomly divided intotwo groups of A (n=40) and B (n=40), which
were obturated with gutta-percha and MTA Filla-pex and AH Plus sealer,
respectively. In both groups, the teeth were randomly subdivided into 2
subgroups. No retreatment was carried out in subgroups A1 and B1, while subgroups
A2 and B2 were retreated with rotary files and a solvent. Then, a push-out test
was performed on four 2-mm slices of each tooth at a distance of 2 mm from the
coronal surface after two weeks of incubation. Data were analyzed with two-way
ANOVA and statistical significance was set at P<0.05. Results. Regardless of the
procedure followed (P<0.001), significant differences were detected in the mean
bond strength values between the two sealers. Irrespective of the sealer type
(P=0.3), no significant differences were revealed by comparing the mean bond
strength values of the study subgroups. Furthermore, no statistically significant
interaction (P=0.5) was found between the treatment and sealer types. Conclusion.
AH Plus sealer exhibited a higher bond strength compared to MTA Fillapex.
Retreatment using rotary files and chloroform had no statistically significant
effect on the bond strength of sealers evaluated in this study.
PMID- 28413594
TI - The effect of repeated preheating of dimethacrylate and silorane-based composite
resins on marginal gap of class V restorations.
AB - Background. One of the problems with composite resin restorations is gap
formation at resin-tooth interface. The present study evaluated the effect of
preheating cycles of silorane- and dimethacrylate-based composite resins on gap
formation at the gingival margins of Class V restorations. Methods. In this in
vitro study, standard Class V cavities were prepared on the buccal surfaces of 48
bovine incisors. For restorative procedure, the samples were randomly divided
into 2 groups based on the type of composite resin (group 1: di-methacrylate
composite [Filtek Z250]; group 2: silorane composite [Filtek P90]) and each group
was randomly divided into 2 subgroups based on the composite temperature (A: room
temperature; B: after 40 preheating cycles up to 55 degrees C). Marginal gaps
were measured using a stereomicroscope at *40 and analyzed with two-way ANOVA.
Inter- and intra-group comparisons were analyzed with post-hoc Tukey tests.
Significance level was defined at P < 0.05. Results. The maximum and minimum gaps
were detected in groups 1-A and 2-B, respectively. The effects of composite resin
type, preheating and interactive effect of these variables on gap formation were
significant (P<0.001). Post-hoc Tukey tests showed greater gap in dimethacrylate
compared to silorane composite resins (P< 0.001). In each group, gap values were
greater in composite resins at room temperature compared to composite resins
after 40 preheating cycles (P<0.001). Conclusion. Gap formation at the gingival
margins of Class V cavities decreased due to preheating of both composite re
sins. Preheating of silorane-based composites can result in the best marginal
adaptation.
PMID- 28413596
TI - Non-syndromic multiple supernumerary premolars: Clinicoradiographic report of
five cases.
AB - Hyperdontia or supernumerary teeth in both arches without any syndromic
manifestation are extremely rare. Supernumerary teeth are commonly associated
with Gardner's syndrome, cleft lip and palate, cleidocranial dysplasia and
trichorhinopha-langeal syndrome. Five cases of non-syndromic multiple premolars
of maxillary and mandibular arches in Indian patients are presented here. This
case series reports three cases with multiple (9 in maximum), bilaterally
impacted and erupted supernumerary teeth and two cases with supernumerary
premolars in non-syndromic cases from Indian patients. Supernumerary teeth can be
present in any region of the oral cavity. Although the occurrence of maxillary
para-premolars is rare, radio-logical investigations play a major and decisive
role in determining the management of such cases.
PMID- 28413597
TI - Concurrent manifestation of clinical hypodontia and blindness: a case report.
AB - A case is reported of a 26-year-old blind man with hypodontia and multiple
apparently underdeveloped impacted teeth. The patient reported that he had
progressively developed visual impairment at the age of 11 years whence he became
totally blind when he turned 12 years. The aim of this report is to open an
academic and professional debate on the challenges of its definitive diagnosis
and appropriate intervention.Blindness is not reported in any of the previously
described syndromes; therefore, concurrent manifestation of "hypodontia,
blindness, failure of eruption and digital lesions" can be proposed as a
syndrome. However, in the absence of genetic studies, it is difficult to
characterize this case with any one of the specifically documented syndromes;
therefore, academic and professional discourse is suggested with regard to
appropriate intervention.
PMID- 28413598
TI - Solitary peripheral ivory osteoma of the mandible presenting with difficulty in
deglutition: a case report.
AB - Osteomas are benign bone tumors which arise from the cortex or medulla of
craniofacial and jaw bones. They are usually asymptomatic or present as slow
growing painless masses. Larger lesions may present with aesthetic (facial
asymmetry) and functional disturbances (jaw deviation, difficulty in breathing,
pain, and sensory deficits). This paper highlights a case of solitary peripheral
osteoma composed of a compact bony mass arising from the lower border of the
mandible in an adult female patient. The lesion presented with discomfort during
deglutition, which was attributed to impingement of muscles of the oral cavity
floor, including the anterior belly of digastric muscle.
PMID- 28413599
TI - Rare features associated with Mobius syndrome: Report of two cases.
AB - Mobius syndrome is a rare congenital disorder with the preliminary diagnostic
criteria of congenital facial and abducent nerve palsy. Involvement of other
cranial nerves, too, is common. Prevalence rate of this syndrome is approximately
1 in 100,000 neonates. It is of unknown etiology with sporadic occurrence.
However, data regarding the occurrence rate in India is limited. Features such as
orofacial malformations, limb defects, and musculoskeletal, behavioral, and
cognitive abnormalities might be associated. A thorough evaluation to identify
the condition and establishing an adequate treatment plan is of utmost important
in this condition. We are reporting clinical and radiographic features of Mobius
syndrome in two cases along with unusual findings of limb and neck deformity.
PMID- 28413600
TI - Screening the use of informed consent forms prior to procedures involving
operative dentistry: ethical aspects.
AB - Background. The present study aimed to screen the knowledge and attitudes of
dentists toward the use of informed consent forms prior to procedures involving
operative dentistry. Methods. A research tool containing questions
(questionnaire) regarding the use of informed consent forms was developed. The
questionnaire consisted of seven questions structured to screen the current
practice in operative dentistry towards the use of informed consent forms.
Results. The questionnaires were distributed among 731 dentists, of which 179
returned them with answers. Sixty-seven dentists reported not using informed
consent forms. The main reasons for not using informed consent forms were: having
a complete dental record signed by the patient (67.2%) and having a good relation
with patients (43.6%). The dentists who reported using informed consent forms
revealed that they obtained them from other dentists and made their own
modifications (35.9%). Few dentists revealed contacting lawyers (1.7%) and
experts in legal dentistry (0.9%) for the development of their informed consent
forms. Conclusion. A high number of dentists working in the field of operative
dentistry behave according to the ethical standards in the clinical practice,
becoming unprotected against ethical and legal actions.
PMID- 28413601
TI - A few of my favorite things: circumscribed interests in autism are not
accompanied by increased attentional salience on a personalized selective
attention task.
AB - BACKGROUND: Autistic individuals commonly show circumscribed or "special"
interests: areas of obsessive interest in a specific category. The present study
investigated what impact these interests have on attention, an aspect of autistic
cognition often reported as altered. In neurotypical individuals, interest and
expertise have been shown to result in an automatic attentional priority for
related items. Here, we examine whether this change in salience is also seen in
autism. METHODS: Adolescents and young adults with and without autism performed a
personalized selective attention task assessing the level of attentional priority
afforded to images related to the participant's specific interests. In addition,
participants performed a similar task with generic images in order to isolate any
effects of interest and expertise. Crucially, all autistic and non-autistic
individuals recruited for this study held a strong passion or interest. As such,
any differences in attention could not be solely attributed to differing
prevalence of interests in the two groups. In both tasks, participants were asked
to perform a central target-detection task while ignoring irrelevant distractors
(related or unrelated to their interests). The level of distractor interference
under various task conditions was taken as an indication of attentional priority.
RESULTS: Neurotypical individuals showed the predicted attentional priority for
the circumscribed interest images but not generic items, reflecting the impact of
their interest and expertise. Contrary to predictions, autistic individuals did
not show this priority: processing the interest-related stimuli only when task
demands were low. Attention to images unrelated to circumscribed interests was
equivalent in the two groups. CONCLUSIONS: These results suggest that despite
autistic individuals holding an intense interest in a particular class of
stimuli, there may be a reduced impact of this prior experience and expertise on
attentional processing. The implications of this absence of automatic priority
are discussed in terms of the behaviors associated with the condition.
PMID- 28413603
TI - Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p
expression to induce STAT3 overexpression.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer
related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading
cause of HCC. Previous studies have demonstrated that expression of the tumor
inhibitor miR-340 is significantly downregulated in HCC tissues compared with
normal liver tissues. However, the precise biological role of miR-340-5p in HBV
HCC and its molecular mechanism of action remain unknown. RESULTS: Expression of
miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected
cells, facilitating migration of liver cancer cells. Signal transducer and
activator of transcription (STAT)3 was found to be a direct functional target of
miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using
qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3
on the migration of HBV-infected cells were evaluated in vitro using Transwell(r)
and wound-healing assays. The expression of E-cadherin and vimentin, associated
with epithelial-mesenchymal transition, was also assessed using Western blotting
after transfection of miR-340-5p mimics and/or STAT3 expression vectors.
Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin
expression, increased vimentin expression, and ultimately, enhanced cell
migration. Re-introduction of the STAT3 CDS led to marked reversal of the
inhibition of cell migration in HBV-infected cells mediated by miR-340-5p.
CONCLUSIONS: Hepatitis B virus promotes the migration of liver cancer cells by
downregulating miR-340-5p expression to induce STAT3 overexpression. Our results
show that STAT3 plays a key role in regulating cell migration in HBV-HCC
involving miR-340-5p.
PMID- 28413602
TI - Do sex differences in CEOAEs and 2D:4D ratios reflect androgen exposure? A study
in women with complete androgen insensitivity syndrome.
AB - BACKGROUND: Studies investigating the influence of perinatal hormone exposure on
sexually differentiated traits would greatly benefit from biomarkers of these
early hormone actions. Click-evoked otoacoustic emissions show sex differences
that are thought to reflect differences in early androgen exposure. Women with
complete androgen insensitivity syndrome (CAIS), who lack androgen action in the
presence of XY-chromosomes, enabled us to study the effect of complete androgen
inaction. The main goal was to investigate a possible link between click-evoked
otoacoustic emissions and effective androgen exposure and, thus, whether this can
be used as a biomarker. In addition, we aimed to replicate the only previous 2nd
vs 4th digit-ratio study in women with CAIS, because despite the widely expressed
criticisms of the validity of this measure as a biomarker for prenatal androgen
exposure, it still is used for this purpose. METHODS: Click-evoked otoacoustic
emissions and digit ratios from women with CAIS were compared to those from
control men and women. RESULTS: The typical sex differences in click-evoked
otoacoustic emissions and digit ratios were replicated in the control groups.
Women with CAIS showed a tendency towards feminine, i.e., larger, click-evoked
otoacoustic emission amplitudes in the right ear, and a significant female
typical, i.e., larger, digit ratio in the right hand. Although these results are
consistent with androgen-dependent development of male-typical click-evoked
otoacoustic emission amplitude and 2nd to 4th digit ratios, the within-group
variability of these two measures was not reduced in women with CAIS compared
with control women. CONCLUSIONS: In line with previous studies, our findings in
CAIS women suggest that additional, non-androgenic, factors mediate male-typical
sexual differentiation of digit ratios and click-evoked otoacoustic emissions.
Consequently, use of these measures in adults as retrospective markers of early
androgen exposure is not recommended.
PMID- 28413604
TI - The role of GLI1 for 5-Fu resistance in colorectal cancer.
AB - Colorectal cancer is a leading cause of cancer-related mortality worldwide, with
Fluorouracil (5-FU)-based chemotherapy as the major treatment for advanced
disease. Many patients with advanced colorectal cancer eventually succumb to the
disease despite some patients responded initially to chemotherapy. Thus,
identifying molecular mechanisms responsible for chemotherapy resistance will
help design novel strategies to treat colorectal cancer. In this study, we
established an acquired 5-FU resistant cell line, LoVo-R, from LoVo cells.
Through exome sequencing, we discovered that elevated GLI1 signaling axis is a
major genetic alteration in the 5-FU resistant cells. Hh signaling, a pathway
essential for embryonic development, is an important regulator for residual
cancer cells. We demonstrated that knockdown of GLI1 or GLI2 sensitized LoVo-R
cells to 5-FU treatment, reduced cell invasiveness. The relevance of our studies
to colorectal cancer patients is reflected by our discovery that high expression
of GLI1 signaling molecules was associated with a high incidence of cancer
relapse and a shorter survival in a larger cohort of colorectal cancer patients
who underwent chemotherapy (containing 5-FU). Taken together, our data
demonstrate the critical role of the GLI1 signaling axis for 5-FU resistance in
colorectal cancer.
PMID- 28149502
TI - An open and transparent process to select ELIXIR Node Services as implemented by
ELIXIR-UK.
AB - ELIXIR is the European infrastructure established specifically for the sharing
and sustainability of life science data. To provide up-to-date resources and
services, ELIXIR needs to undergo a continuous process of refreshing the services
provided by its national Nodes. Here we present the approach taken by ELIXIR-UK
to address the advice by the ELIXIR Scientific Advisory Board that Nodes need to
develop " mechanisms to ensure that each Node continues to be representative of
the Bioinformatics efforts within the country". ELIXIR-UK put in place an open
and transparent process to identify potential ELIXIR resources within the UK
during late 2015 and early to mid-2016. Areas of strategic strength were
identified and Expressions of Interest in these priority areas were requested
from the UK community. Criteria were established, in discussion with the ELIXIR
Hub, and prospective ELIXIR-UK resources were assessed by an independent
committee set up by the Node for this purpose. Of 19 resources considered, 14
were judged to be immediately ready to be included in the UK ELIXIR Node's
portfolio. A further five were placed on the Node's roadmap for future
consideration for inclusion. ELIXIR-UK expects to repeat this process regularly
to ensure its portfolio continues to reflect its community's strengths.
PMID- 28413606
TI - Comparing efficacy of a sweep net and a dip method for collection of mosquito
larvae in large bodies of water in South Africa.
AB - In this study we tested an alternative method for collecting mosquito larvae
called the sweep net catch method and compared its efficiency to that of the
traditional dip method. The two methods were compared in various water bodies
within Kruger National Park and Lapalala Wilderness area, South Africa. The sweep
net catch method performed 5 times better in the collection of Anopheles larvae
and equally as well as the dip method in the collection of Culex larvae (p =8.58
x 10 -5). Based on 15 replicates the collector's experience level did not play a
significant role in the relative numbers of larvae collected using either method.
This simple and effective sweep net catch method will greatly improve the
mosquito larval sampling capacity in the field setting.
PMID- 28408973
TI - A multi-scale computational model of the effects of TMS on motor cortex.
AB - The detailed biophysical mechanisms through which transcranial magnetic
stimulation (TMS) activates cortical circuits are still not fully understood.
Here we present a multi-scale computational model to describe and explain the
activation of different pyramidal cell types in motor cortex due to TMS. Our
model determines precise electric fields based on an individual head model
derived from magnetic resonance imaging and calculates how these electric fields
activate morphologically detailed models of different neuron types. We predict
neural activation patterns for different coil orientations consistent with
experimental findings. Beyond this, our model allows us to calculate activation
thresholds for individual neurons and precise initiation sites of individual
action potentials on the neurons' complex morphologies. Specifically, our model
predicts that cortical layer 3 pyramidal neurons are generally easier to
stimulate than layer 5 pyramidal neurons, thereby explaining the lower
stimulation thresholds observed for I-waves compared to D-waves. It also shows
differences in the regions of activated cortical layer 5 and layer 3 pyramidal
cells depending on coil orientation. Finally, it predicts that under standard
stimulation conditions, action potentials are mostly generated at the axon
initial segment of cortical pyramidal cells, with a much less important
activation site being the part of a layer 5 pyramidal cell axon where it crosses
the boundary between grey matter and white matter. In conclusion, our
computational model offers a detailed account of the mechanisms through which TMS
activates different cortical pyramidal cell types, paving the way for more
targeted application of TMS based on individual brain morphology in clinical and
basic research settings.
PMID- 28413608
TI - Evidence synthesis and decision modelling to support complex decisions:
stockpiling neuraminidase inhibitors for pandemic influenza usage.
AB - Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a
defence against pandemic influenza is a significant public health policy decision
that must be made despite a lack of conclusive evidence from randomised
controlled trials regarding the effectiveness of NAIs on important clinical end
points such as mortality. The objective of this study was to determine whether
NAIs should be stockpiled for treatment of pandemic influenza on the basis of
current evidence. Methods: A decision model for stockpiling was designed. Data on
previous pandemic influenza epidemiology was combined with data on the
effectiveness of NAIs in reducing mortality obtained from a recent individual
participant meta-analysis using observational data. Evidence synthesis techniques
and a bias modelling method for observational data were used to incorporate the
evidence into the model. The stockpiling decision was modelled for adults (>=16
years old) and the United Kingdom was used as an example. The main outcome was
the expected net benefits of stockpiling in monetary terms. Health benefits were
estimated from deaths averted through stockpiling. Results: After adjusting for
biases in the estimated effectiveness of NAIs, the expected net benefit of
stockpiling in the baseline analysis was L444 million, assuming a willingness to
pay of L20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile
NAIs. There was a greater probability that the stockpile would not be utilised
than utilised. However, the rare but catastrophic losses from a severe pandemic
justified the decision to stockpile. Conclusions: Taking into account the
available epidemiological data and evidence of effectiveness of NAIs in reducing
mortality, including potential biases, a decision maker should stockpile anti
influenza medication in keeping with the postulated decision rule.
PMID- 28413609
TI - An ensemble-based Cox proportional hazards regression framework for predicting
survival in metastatic castration-resistant prostate cancer (mCRPC) patients.
AB - From March through August 2015, nearly 60 teams from around the world
participated in the Prostate Cancer Dream Challenge (PCDC). Participating teams
were faced with the task of developing prediction models for patient survival and
treatment discontinuation using baseline clinical variables collected on
metastatic castrate-resistant prostate cancer (mCRPC) patients in the comparator
arm of four phase III clinical trials. In total, over 2,000 mCRPC patients
treated with first-line docetaxel comprised the training and testing data sets
used in this challenge. In this paper we describe: (a) the sub-challenges
comprising the PCDC, (b) the statistical metrics used to benchmark prediction
performance, (c) our analytical approach, and finally (d) our team's overall
performance in this challenge. Specifically, we discuss our curated, ad-hoc,
feature selection (CAFS) strategy for identifying clinically important risk
predictors, the ensemble-based Cox proportional hazards regression framework used
in our final submission, and the adaptation of our modeling framework based on
the results from the intermittent leaderboard rounds. Strong predictors of
patient survival were successfully identified utilizing our model building
approach. Several of the identified predictors were new features created by our
team via strategically merging collections of weak predictors. In each of the
three intermittent leaderboard rounds, our prediction models scored among the top
four models across all participating teams and our final submission ranked 9 th
place overall with an integrated area under the curve (iAUC) of 0.7711 computed
in an independent test set. While the prediction performance of teams placing
between 2 nd- 10 th (iAUC: 0.7710-0.7789) was better than the current gold
standard prediction model for prostate cancer survival, the top-performing team,
FIMM-UTU significantly outperformed all other contestants with an iAUC of 0.7915.
In summary, our ensemble-based Cox regression framework with CAFS resulted in
strong overall performance for predicting prostate cancer survival and represents
a promising approach for future prediction problems.
PMID- 28413610
TI - Animating and exploring phylogenies with fibre plots.
AB - Despite the progress that has been made in the visualisation of information since
Haeckel's time, phylogenetic visualisation has moved forward remarkably little.
In this brief essay, I give a short review of what I consider to be some recent
major advances, and outline a new kind of phylogenetic visualisation. This new
graphic, the fibre plot, uses the metaphor of sections through a tree to describe
change in a phylogeny. As an animation, I suggest it is a powerful method to help
interpret large phylogenetic hypotheses, although snapshots of it can also be
displayed. As we enter the Anthropocene, I argue there has never been a greater
need to know humanity's true place in the world, as depicted in the tree of life.
PMID- 28413611
TI - Expression of lectin-like transcript-1 in human tissues.
AB - Background: Receptor-ligand pairs of C-type lectin-like proteins have been shown
to play an important role in cross talk between lymphocytes, as well as in immune
responses within concrete tissues and structures, such as the skin or the
germinal centres. The CD161-Lectin-like Transcript 1 (LLT1) pair has gained
particular attention in recent years, yet a detailed analysis of LLT1
distribution in human tissue is lacking. One reason for this is the limited
availability and poor characterisation of anti-LLT1 antibodies. Methods: We
assessed the staining capabilities of a novel anti-LLT1 antibody clone (2H7),
both by immunohistochemistry and flow cytometry, showing its efficiency at LLT1
recognition in both settings. We then analysed LLT1 expression in a wide variety
of human tissues. Results: We found LLT1 expression in circulating B cells and
monocytes, but not in lung and liver-resident macrophages. We found strikingly
high LLT1 expression in immune-privileged sites, such as the brain, placenta and
testes, and confirmed the ability of LLT1 to inhibit NK cell function.
Conclusions: Overall, this study contributes to the development of efficient
tools for the study of LLT1. Moreover, its expression in different healthy human
tissues and, particularly, in immune-privileged sites, establishes LLT1 as a good
candidate as a regulator of immune responses.
PMID- 28413612
TI - Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in
blood pressure control and recent pivotal trials of RAAS blockade in heart
failure and diabetic nephropathy.
AB - The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the
physiology of blood pressure control and the pathophysiology of hypertension
(HTN) with effects on vascular tone, sodium retention, oxidative stress,
fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents
have been available to treat HTN since the 1970s and newer medications are being
developed. In this review, we will (1) examine new anti-hypertensive medications
affecting the RAAS, (2) evaluate recent studies that help provide a better
understanding of which patients may be more likely to benefit from RAAS blockade,
and (3) review three recent pivotal randomized trials that involve newer RAAS
blocking agents and inform clinical practice.
PMID- 28413614
TI - The PathLinker app: Connect the dots in protein interaction networks.
AB - PathLinker is a graph-theoretic algorithm for reconstructing the interactions in
a signaling pathway of interest. It efficiently computes multiple short paths
within a background protein interaction network from the receptors to
transcription factors (TFs) in a pathway. We originally developed PathLinker to
complement manual curation of signaling pathways, which is slow and painstaking.
The method can be used in general to connect any set of sources to any set of
targets in an interaction network. The app presented here makes the PathLinker
functionality available to Cytoscape users. We present an example where we used
PathLinker to compute and analyze the network of interactions connecting proteins
that are perturbed by the drug lovastatin.
PMID- 28413615
TI - Monitoring disease activity and severity in lupus.
AB - Background: Systemic lupus erythematosus (SLE) is a relatively uncommon disease
of young females in Pakistan. Usually, it has a relapsing-remitting course with
variable severity and disease activity. Amongst the different clinical and
laboratory parameters used to monitor disease activity in lupus, mean platelet
volume (MPV) is a novel biomarker. Although MPV has been studied in other
rheumatological conditions like rheumatoid arthritis, its role in adult SLE needs
to be defined, especially in Pakistan. Methods: The aim of this study was to
evaluate the role of MPV as a biomarker of disease activity in SLE. This study
included 25 patients with active SLE, and another 25 participants with stable,
inactive lupus. MPV was measured in each group and compared using SPSS version
16. MPV was also correlated with SLE disease activity index (SLEDAI) and
erythrocyte sedimentation rate (ESR). Independent sample t-test and Pearson's
correlation tests were applied. Sensitivity and specificity of MPV were checked
through ROC analysis. Results: The MPV of patients with active SLE (n=25, mean
[M]=7.12, SD=1.01) was numerically lower than those in the inactive-SLE group
(n=25, M= 10.12, SD=0.97), and this was statistically significant ( P<0.001). MPV
had an inverse relationship with both ESR (r=-0.93, P<0.001) and SLEDAI (r=
0.94, P<0.001). However, there was a strong positive correlation between ESR and
SLEDAI (r=0.95, P<0.001). For MPV, a cutoff value of less than 8.5fl had a
sensitivity of 92% and a specificity of 100% ( P< 0.001). Conclusions: Higher
disease activity in SLE is associated with a correspondingly low MPV.
PMID- 28413613
TI - The rise of photoresponsive protein technologies applications in vivo: a
spotlight on zebrafish developmental and cell biology.
AB - The zebrafish ( Danio rerio) is a powerful vertebrate model to study cellular and
developmental processes in vivo. The optical clarity and their amenability to
genetic manipulation make zebrafish a model of choice when it comes to applying
optical techniques involving genetically encoded photoresponsive protein
technologies. In recent years, a number of fluorescent protein and optogenetic
technologies have emerged that allow new ways to visualize, quantify, and perturb
developmental dynamics. Here, we explain the principles of these new tools and
describe some of their representative applications in zebrafish.
PMID- 28413616
TI - -A curated transcriptomic dataset collection relevant to embryonic development
associated with in vitro fertilization in healthy individuals and patients with
polycystic ovary syndrome.
AB - The collection of large-scale datasets available in public repositories is
rapidly growing and providing opportunities to identify and fill gaps in
different fields of biomedical research. However, users of these datasets should
be able to selectively browse datasets related to their field of interest. Here
we made available a collection of transcriptome datasets related to human
follicular cells from normal individuals or patients with polycystic ovary
syndrome, in the process of their development, during in vitro fertilization.
After RNA-seq dataset exclusion and careful selection based on study description
and sample information, 12 datasets, encompassing a total of 85 unique
transcriptome profiles, were identified in NCBI Gene Expression Omnibus and
uploaded to the Gene Expression Browser (GXB), a web application specifically
designed for interactive query and visualization of integrated large-scale data.
Once annotated in GXB, multiple sample grouping has been made in order to create
rank lists to allow easy data interpretation and comparison. The GXB tool also
allows the users to browse a single gene across multiple projects to evaluate its
expression profiles in multiple biological systems/conditions in a web-based
customized graphical views. The curated dataset is accessible at the following
link: http://ivf.gxbsidra.org/dm3/landing.gsp.
PMID- 28413617
TI - Automated Wormscan.
AB - There has been a recent surge of interest in computer-aided rapid data
acquisition to increase the potential throughput and reduce the labour costs of
large scale Caenorhabditis elegans studies. We present Automated WormScan, a low
cost, high-throughput automated system using commercial photo scanners, which is
extremely easy to implement and use, capable of scoring tens of thousands of
organisms per hour with minimal operator input, and is scalable. The method does
not rely on software training for image recognition, but uses the generation of
difference images from sequential scans to identify moving objects. This approach
results in robust identification of worms with little computational demand. We
demonstrate the utility of the system by conducting toxicity, growth and
fecundity assays, which demonstrate the consistency of our automated system, the
quality of the data relative to manual scoring methods and congruity with
previously published results.
PMID- 28357048
TI - Bibliometric analysis of Oropouche research: impact on the surveillance of
emerging arboviruses in Latin America.
AB - Given the emergence and reemergence of viral diseases, particularly in Latin
America, we would like to provide an analysis of the patterns of research and
publication on Oropouche virus (OROV). We also discuss the implications of recent
epidemics in certain areas of South America, and how more clinical and
epidemiological information regarding OROV is urgently needed.
PMID- 28413619
TI - Picopore: A tool for reducing the storage size of Oxford Nanopore Technologies
datasets without loss of functionality.
AB - Oxford Nanopore Technologies' (ONT) MinION and PromethION long-read sequencing
technologies are emerging as genuine alternatives to established Next-Generation
Sequencing technologies. A combination of the highly redundant file format and a
rapid increase in data generation have created a significant problem both for
immediate data storage on MinION-capable laptops, and for long-term storage on
lab data servers. We developed Picopore, a software suite offering three methods
of compression. Picopore's lossless and deep lossless methods provide a 25% and
44% average reduction in size, respectively, without removing any data from the
files. Picopore's raw method provides an 88% average reduction in size, while
retaining biologically relevant data for the end-user. All methods have the
capacity to run in real-time in parallel to a sequencing run, reducing demand for
both immediate and long-term storage space.
PMID- 28413620
TI - Case Report: Sciatic nerve schwannoma - a rare cause of sciatica.
AB - Herein we report a rare case of a sciatic nerve schwannoma causing sciatica in a
69-year-old female. Sciatic nerve schwannoma is a rare entity. It should always
be considered as a possible cause of sciatica in patients that present with
symptoms of sciatica with no prolapsed disc in the lumbar spine and a negative
crossed straight leg raise test. Timely diagnosis and complete excision of the
lesion leads to complete resolution of the symptoms of such patients.
PMID- 28413621
TI - Recent Advances in Pediatric Ventilatory Assistance.
AB - In this review on respiratory assistance, we aim to discuss the following recent
advances: the optimization and customization of mechanical ventilation, the use
of high-frequency oscillatory ventilation, and the role of noninvasive
ventilation. The prevention of ventilator-induced lung injury and diaphragmatic
dysfunction is now a key aspect in the management of mechanical ventilation,
since these complications may lead to higher mortality and prolonged length of
stay in intensive care units. Different physiological measurements, such as
esophageal pressure, electrical activity of the diaphragm, and volumetric
capnography, may be useful objective tools to help guide ventilator assistance.
Companies that design medical devices including ventilators and respiratory
monitoring platforms play a key role in knowledge application. The creation of a
ventilation consortium that includes companies, clinicians, researchers, and
stakeholders could be a solution to promote much-needed device development and
knowledge implementation.
PMID- 28413622
TI - Insight into skin cell-based osteogenesis: a review.
AB - For decades, researchers have been fascinated by the strategy of using cell
therapy for bone defects; some progress in the field has been made. Owing to its
ample supply and easy access, skin, the largest organ in the body, has gained
attention as a potential source of stem cells. Despite extensive applications in
skin and nerve regeneration, an increasing number of reports indicate its
potential use in bone tissue engineering and regeneration. Unfortunately, few
review articles are available to outline current research efforts in skin-based
osteogenesis. This review first summarizes the latest findings on stem cells or
progenitors in skin and their niches and then discusses the strategies of skin
cell-based osteogenesis. We hope this article elucidates this topic and generates
new ideas for future studies.
PMID- 28413624
TI - Recent advances in understanding spondyloarthritis.
AB - This review is concerned with a number of recent publications that contribute to
current thinking on the pathogenesis of spondyloarthritis. The areas covered
include the lymphocyte population in the enthesis, which is thought to drive
enthesitis, and hence clinical manifestations. The debate on how HLA-B27 is
implicated in inflammation is also considered, together with recent and
contradictory evidence on the effects of the peptide-trimming enzyme ERAP1 on B27
expression and hence susceptibility to spondylitis. Lastly, a recent report on
the role of the gut microbiome in an important model of spondyloarthritis is
considered.
PMID- 28413623
TI - Glutamate plasticity woven through the progression to alcohol use disorder: a
multi-circuit perspective.
AB - Glutamate signaling in the brain is one of the most studied targets in the
alcohol research field. Here, we report the current understanding of how the
excitatory neurotransmitter glutamate, its receptors, and its transporters are
involved in low, episodic, and heavy alcohol use. Specific animal behavior
protocols can be used to assess these different drinking levels, including two
bottle choice, operant self-administration, drinking in the dark, the alcohol
deprivation effect, intermittent access to alcohol, and chronic intermittent
ethanol vapor inhalation. Importantly, these methods are not limited to a
specific category, since they can be interchanged to assess different states in
the development from low to heavy drinking. We encourage a circuit-based
perspective beyond the classic mesolimbic-centric view, as multiple structures
are dynamically engaged during the transition from positive- to negative-related
reinforcement to drive alcohol drinking. During this shift from lower-level
alcohol drinking to heavy alcohol use, there appears to be a shift from
metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate
receptor-related processes. Despite high efficacy of the glutamate-related
pharmaceutical acamprosate in animal models of drinking, it is ineffective as
treatment in the clinic. Therefore, research needs to focus on other promising
glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms
or both.
PMID- 28413625
TI - HIV-associated neurocognitive disorders: recent advances in pathogenesis,
biomarkers, and treatment.
AB - HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma
viral suppression by antiretroviral agents. In fact, the prevalence of milder
subtypes of cognitive impairment is increasing. Neuropsychologic testing remains
the "gold standard" of diagnosis; however, this is time consuming and costly in a
resource-poor environment. Recently developed screening tools, such as CogState
and the revised HIV dementia scale, have very good sensitivity and specificity in
the more severe stages of HAND. However, questions remain regarding the utility
of, optimal population for, and insensitivity of tests in mild HAND. Recognition
of ongoing viral persistence and the inflammatory milieu in the central nervous
system (CNS) has advanced our understanding of the pathogenesis of HAND and
facilitated the development of biomarkers of CNS disease. The importance of the
monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral
proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor
neurotropism has been identified. Whilst biomarkers demonstrate monocyte
activation, inflammation, and neuronal injury, they remain limited in their
clinical utility. The improved understanding of pathogenic mechanisms has led to
novel approaches to the treatment of HAND; however, despite these advances, the
optimal management is still undefined.
PMID- 28413627
TI - Advancing psychological therapies for chronic pain.
AB - There is a strong tradition of therapy development and evaluation in the field of
psychological interventions for chronic pain. However, despite this research
production, the effects of treatments remain uncertain, and treatment development
has stalled. This review summarises the current evidence but focusses on
promising areas for improvement. Advancing psychological therapies for chronic
pain will come from a radical re-imagining of the content, delivery, place, and
control of therapy. The next generation of therapeutic interventions will also
need alternative methods of measurement and evaluation, and options are
discussed.
PMID- 28413626
TI - Non-infectious chemotherapy-associated acute toxicities during childhood acute
lymphoblastic leukemia therapy.
AB - During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be
affected by severe acute side effects, the most common being opportunistic
infections, mucositis, central or peripheral neuropathy (or both), bone
toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction
syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and
hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase
associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non
infectious acute toxicities are associated with clinically useful risk factors,
and across study groups there has been wide diversity in toxicity definitions,
capture strategies, and reporting, thus hampering meaningful comparisons of
toxicity incidences for different leukemia protocols. Since treatment of acute
lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there
is a need for strategies for assessing the burden of toxicities in the overall
evaluation of anti-leukemic therapy programs.
PMID- 28413628
TI - American Society for Enhanced Recovery (ASER) and Perioperative Quality
Initiative (POQI) Joint Consensus Statement on Optimal Analgesia within an
Enhanced Recovery Pathway for Colorectal Surgery: Part 2-From PACU to the
Transition Home.
AB - BACKGROUND: Within an enhanced recovery pathway (ERP), the approach to treating
pain should be multifaceted and the goal should be to deliver "optimal
analgesia", which we define in this paper as a technique that optimizes patient
comfort and facilitates functional recovery with the fewest medication side
effects. METHODS: With input from a multidisciplinary, international group of
experts and through a structured review of the literature and use of a modified
Delphi method, we achieved consensus surrounding the topic of optimal analgesia
in the perioperative period for colorectal surgery patients. DISCUSSION: As a
part of the first Perioperative Quality Improvement (POQI) workgroup meeting, we
sought to develop a consensus document describing a comprehensive, yet rational
and practical, approach for developing an evidence-based plan for achieving
optimal analgesia, specifically for a colorectal surgery within an ERP. The goal
was twofold: (a) that application of this process would lead to improved patient
outcomes and (b) that investigation of the questions raised would identify
knowledge gaps to aid the direction for research into analgesia within ERPs in
the years to come. This document details the evidence for a wide range of
analgesic components, with particular focus on care in the post-anesthesia care
unit, general care ward, and transition to home after discharge. The preoperative
and operative consensus statement for analgesia was covered in Part 1 of this
paper. The overall conclusion is that the combination of analgesic techniques
employed in the perioperative period is not important as long as it is effective
in delivering the goal of "optimal analgesia" as set forth in this document.
PMID- 28413631
TI - Screening and contact precautions - A survey on infection control measures for
multidrug-resistant bacteria in German university hospitals.
AB - To assess the scope of infection control measures for multidrug-resistant
bacteria in high-risk settings, a survey among university hospitals was
conducted. Fourteen professionals from 8 sites participated. Reported policies
varied largely with respect to the types of wards conducting screening, sample
types used for screening and implementation of contact precautions. This
variability among sites highlights the need for an evidence-based consensus of
current infection control policies.
PMID- 28413629
TI - American Society for Enhanced Recovery (ASER) and Perioperative Quality
Initiative (POQI) joint consensus statement on optimal analgesia within an
enhanced recovery pathway for colorectal surgery: part 1-from the preoperative
period to PACU.
AB - BACKGROUND: Within an enhanced recovery pathway (ERP), the approach to treating
pain should be multifaceted and the goal should be to deliver "optimal
analgesia," which we define in this paper as a technique that optimizes patient
comfort and facilitates functional recovery with the fewest medication side
effects. METHODS: With input from a multi-disciplinary, international group of
clinicians, and through a structured review of the literature and use of a
modified Delphi method, we achieved consensus surrounding the topic of optimal
analgesia in the perioperative period for colorectal surgery patients.
DISCUSSION: As a part of the first Perioperative Quality Improvement (POQI)
workgroup meeting, we sought to develop a consensus document describing a
comprehensive, yet rational and practical, approach for developing an evidence
based plan for achieving optimal analgesia, specifically for a colorectal surgery
ERP. The goal was two-fold: (a) that application of this process would lead to
improved patient outcomes and (b) that investigation of the questions raised
would identify knowledge gaps to aid the direction for research into analgesia
within ERPs in the years to come. This document details the evidence for a wide
range of analgesic components, with particular focus from the preoperative period
to the post-anesthesia care unit. The overall conclusion is that the combination
of analgesic techniques employed in the perioperative period is not important as
long as it is effective in delivering the goal of optimal analgesia as set forth
in this document.
PMID- 28413632
TI - Is In-Vivo laparoscopic simulation learning a step forward in the Undergraduate
Surgical Education?
AB - BACKGROUND: Essentials Skills in the Management of Surgical Cases - ESMSC is an
International Combined Applied Surgical Science and Wet Lab course addressed at
the Undergraduate level. Laparoscopic Skills is a fundamental element of Surgical
Education and various Simulation-Based Learning (SBL) models have been endorsed.
This study aims to explore if there is any significant difference in delegates'
performance depending on whether they completed In Vivo module prior to the
equivalent in the laparoscopic simulator. MATERIALS AND METHODS: 37 Medical
Students from various EU countries were divided in 2 groups, and both completed
the "Fundamentals in Laparoscopic Surgery" module in the Dry-lab Laparoscopic
Simulator as well as the same module "In Vivo" on a swine model. Group A (18
students, 48.6%) completed the "Fundamentals in Laparoscopic Surgery - FLS"
module prior to the "In Vivo", whereas group B completed the "In Vivo" module
first. Direct Observation of Procedural Skills (DOPS) were used to assess
delegates' performance. RESULTS: The mean DOPS scores for the "FLS" and "In Vivo"
models were 2.27 +/- 0.902 and 2.03 +/- 0.833, respectively, and the delegates'
performance was not statistically significantly different between them (p =
0.128). There was no statistically significant difference in the scores among
different gender, year of study, school and handedness groups. The alteration in
the sequence between Dry-lab "FLS" and "In Vivo" modules did not affect the
performance in neither the "FLS" nor the "In Vivo" models. CONCLUSIONS: The
inexpensive, but low-fidelity "FLS" model could serve an equal alternative
Simulation-Based Learning model for the early undergraduate training. Our study
demonstrated that high fidelity In Vivo simulation for laparoscopic skills does
not affect significantly the improvement in the delegates' performance at the
undergraduate level. Further studies should be conducted to identify at which
stage of training should high fidelity simulation be introduced.
PMID- 28413630
TI - Patient healthcare trajectory. An essential monitoring tool: a systematic review.
AB - BACKGROUND: Patient healthcare trajectory is a recent emergent topic in the
literature, encompassing broad concepts. However, the rationale for studying
patients' trajectories, and how this trajectory concept is defined remains a
public health challenge. Our research was focused on patients' trajectories based
on disease management and care, while also considering medico-economic aspects of
the associated management. We illustrated this concept with an example: a
myocardial infarction (MI) occurring in a patient's hospital trajectory of care.
The patient follow-up was traced via the prospective payment system. We applied a
semi-automatic text mining process to conduct a comprehensive review of patient
healthcare trajectory studies. This review investigated how the concept of
trajectory is defined, studied and what it achieves. METHODS: We performed a
PubMed search to identify reports that had been published in peer-reviewed
journals between January 1, 2000 and October 31, 2015. Fourteen search questions
were formulated to guide our review. A semi-automatic text mining process based
on a semantic approach was performed to conduct a comprehensive review of patient
healthcare trajectory studies. Text mining techniques were used to explore the
corpus in a semantic perspective in order to answer non-a priori questions.
Complementary review methods on a selected subset were used to answer a priori
questions. RESULTS: Among the 33,514 publications initially selected for
analysis, only 70 relevant articles were semi-automatically extracted and
thoroughly analysed. Oncology is particularly prevalent due to its already well
established processes of care. For the trajectory thema, 80% of articles were
distributed in 11 clusters. These clusters contain distinct semantic information,
for example health outcomes (29%), care process (26%) and administrative and
financial aspects (16%). CONCLUSION: This literature review highlights the recent
interest in the trajectory concept. The approach is also gradually being used to
monitor trajectories of care for chronic diseases such as diabetes, organ failure
or coronary artery and MI trajectory of care, to improve care and reduce costs.
Patient trajectory is undoubtedly an essential approach to be further explored in
order to improve healthcare monitoring.
PMID- 28413633
TI - Pluripotent stem cells to hepatocytes, the journey so far.
AB - Over the past several years, there has been substantial progress in the field of
regenerative medicine, which has enabled new possibilities for research and
clinical application. For example, there are ongoing efforts directed at
generating functional hepatocytes from adult-derived pluripotent cells for
toxicity screening, generating disease models or, in the longer term, for the
treatment of liver failure. In the present review, the authors summarise recent
developments in regenerative medicine and pluripotent stem cells, the methods and
tissues used for reprogramming and the differentiation of induced pluripotent
stem cells (iPSCs) into hepatocyte-like cells. In addition, the hepatic disease
models developed using iPSC technologies are discussed, as well as the potential
for gene editing.
PMID- 28413634
TI - Involvement of regucalcin gene promoter region-related protein-p117, a
transcription factor, in human obesity.
AB - Regucalcin gene promoter region-related protein-p117 (RGPR-p117; gene symbol,
rgpr-117) was identified in 2001 as a novel transcription factor that
specifically binds to a nuclear factor I consensus motif, TTGGC(N)6CC in the
promoter region of the regucalcin (rgn) gene. The human RGPR-p117 gene consists
of 26 exons spanning ~4.1 kbp and is localized on chromosome 1q25.2. The nuclear
translocation of cytoplasm RGPR-p117 is mediated via the protein kinase C
dependent signaling pathway. Overexpression of RGPR-p117 enhances the
transcription activity of rgn, and a protective effect on cell death by
inhibition of gene expression levels of caspase-3, caspase-8 and FADD proteins
that possess the TTGGC motif in the promoter region of those genes was revealed.
RGPR-p117 has a crucial role as a transcription factor. Notably, RGPR-p117 was
shown to localize in the plasma membranes, mitochondria and microsomes
(endoplasmic reticulum; ER). RGPR-p117, which is located in the ER, was also
shown to have a role as an ER export factor implicated in the transports of
proteins and lipids. As a result of this finding, it was proposed in 2007 that
RGPR-p117 is renamed SEC 16 homolog B, endoplasmic reticulum export factor
(SEC16B). Recently, there is increasing evidence that RGPR-p117/SEC16B may be
involved in human obesity. Thus, the current review presents data regarding the
involvement of RGPR-p117 in human obesity.
PMID- 28413635
TI - Role of amyloid beta protein receptors in mediating synaptic plasticity.
AB - There are few diseases in modern biomedicine that have garnered as much
scientific interest and public concern as Alzheimer's disease (AD). The amyloid
hypothesis has become the dominant model of AD pathogenesis; however, the details
of the hypothesis are changing over time. Recently, given the increasing
recognition, subtle effects of amyloid beta protein (Abeta) on synaptic efficacy
may be critical to AD progression. Synaptic plasticity is the important
neurochemical foundation of learning and memory. Recent studies have identified
that soluble Abeta oligomers combine with certain receptors to impair synaptic
plasticity in AD, which advanced the amyloid hypothesis. The aim of the present
review was to summarize the role of Abeta-relevant receptors in regulating
synaptic plasticity and their downstream signaling cascades, which may provide
novel insights into the understanding of the pathogenesis of AD and the
development of therapeutic strategies to slow down the progression of AD
associated memory decline in the early stages.
PMID- 28413636
TI - Nuclear magnetic resonance metabolomics and human liver diseases: The principles
and evidence associated with protein and carbohydrate metabolism.
AB - During the last decade, metabolomics has become widely used in the field of human
diseases. Numerous studies have demonstrated that this is a powerful technique
for improving the understanding, diagnosis and management of various types of
liver disease, such as acute and chronic liver diseases, and liver
transplantation. Nuclear magnetic resonance (NMR) spectroscopy is one of the two
most commonly applied methods for metabolomics. The aim of the present review was
to investigate the results from recent key publications focusing on aspects of
protein and carbohydrate metabolism. The review includes existing procedures,
which are currently used for NMR data acquisition and statistical analysis. In
addition, notable results obtained by these studies on protein and carbohydrate
metabolism concerning human liver diseases are presented.
PMID- 28413637
TI - Correlation of survivin and B-cell lymphoma 2 expression with pathological
malignancy and anti-apoptotic properties of glial cell tumors.
AB - Apoptosis, whose mechanism remains unclear, is regulated by multiple factors. B
cell lymphoma 2 (Bcl-2) is a well-known anti-apoptotic mediator. Survivin is also
a recently recognized novel family inhibitor of apoptosis protein, which inhibits
apoptosis via a pathway distinct from Bcl-2 family members. Survivin and Bcl-2
are expressed in various types of human cancer. In the present study, survivin
and Bcl-2 expression were characterized in glial cell tumors, and the correlation
with pathological malignancy and anti-apoptotic properties were investigated.
Fifty-eight patients who had undergone surgical resection for glial cell tumors
were evaluated. The pathological types of glial cell tumors were categorized
according to the World Health Organization classification. Survivin and Bcl-2
expression levels were investigated by western blot analysis, and apoptosis was
detected by DNA fragmentation analysis. The anti-apoptotic rate of glial cell
tumors was calculated in tumor samples according to the expression of survivin
and Bcl-2 or co-expression. Survivin was characterized in 60.3%, and Bcl-2 was
expressed in 43.1% of glioma samples. Co-expression of survivin and Bcl-2 was
observed in 25.9% of the tumor specimens. Survivin expression in astrocytic
tumors was identified to be significantly associated with the pathological grade
(P<0.05); however, Bcl-2 was not (P>0.05). Anti-apoptotic rate of glial cell
tumors were detected in 91.4, 92.0 and 100% of patients exhibiting survivin, Bcl
2 or co-expression, respectively. However, the difference in anti-apoptotic
frequency between the three groups was not identified to be statistically
significant (P>0.05). The present study suggests that survivin expression is
correlated with pathological grades of gliomas. In addition, the expression of
survivin or Bcl-2 exerts potent anti-apoptotic properties in gliomas. Thus,
survivin or Bcl-2 may serve as potential targets for inducing the apoptosis of
gliomas.
PMID- 28413638
TI - Serologic testing of a panel of five antibodies in inflammatory bowel diseases:
Diagnostic value and correlation with disease phenotype.
AB - The aim of the present study was to evaluate the diagnostic value of five
serological antibodies, perinuclear antineutrophil cytoplasmic antibody (pANCA),
anti-Saccharomyces cerevisiae antibodies [ASCA; ASCA-immunoglobulin (IgG)and ASCA
IgA], Escherichia coli outer membrane porin C antibody (anti-OmpC) and CBir1
flagellin antibody for detection in inflammatory bowel diseases. Whether the
antibody status correlated with the disease phenotype was also evaluated. Sera
from 71 patients with Crohn's disease (CD), 41 patients with ulcerative colitis
(UC), 78 patients with other gastrointestinal diseases and 31 healthy control
subjects were investigated. Clinical data were gathered at the time of serum
sampling and enzyme-linked immunosorbent assay was used to determine titers of
the above mentioned five antibodies. The pANCA test exhibited a sensitivity of
53.7% for UC and the ASCA test had a sensitivity of 66.2% for CD. The prevalence
of anti-OmpC was significantly higher in CD than in intestinal tuberculosis (TB),
indicating that anti-OmpC may be a serologic marker distinguishing CD from TB.
The pANCA+/ASCA- exhibited the best specificity for differentiating between CD
and UC. In UC, the presence of pANCA was greater in the patients with moderate to
severe activity than in those with mild activity. ASCA was more positive in ileal
CD. Furthermore, positive ASCA-IgG or anti-OmpC implied that complicated CD and
pANCA was associated with colonic CD. Seropositivity of anti-CBir1 was lowest in
colonic CD.
PMID- 28413639
TI - Calprotectin in serum and zonulin in serum and feces are elevated after
introduction of a diet with lower carbohydrate content and higher fiber, fat and
protein contents.
AB - Calprotectin is a marker of inflammation and zonulin is a marker of intestinal
permeability. Diets with lower carbohydrate content and higher contents of fat,
fiber and protein, e.g., Okinawan-based diet, are considered to reduce
inflammation and intestinal permeability. The aim of the present study was to
evaluate calprotectin and zonulin levels in serum and feces after intervention
with an Okinawan-based Nordic diet. Thirty patients (17 women) with type 2
diabetes, mean age 57.5+/-8.2 years, BMI 29.9+/-4.1 kg/m2, were served the diet
during 12 weeks, and were followed for another 16 weeks. Anthropometric and
metabolic parameters were registered. Fasting levels of calprotectin and zonulin
in serum and feces, and hormones in plasma, were measured by Luminex or ELISA
before study start and after 12 and 28 weeks. Calprotectin in serum tended to be
increased (P=0.074) after 12 weeks. Zonulin in serum and feces were elevated
after 12 weeks (P=0.019 vs. P<0.001), and remained elevated in serum after 28
weeks (P=0.014). In contrast to baseline, there was a correlation between
calprotectin and zonulin in serum and feces after dietary intervention (P=0.025
vs. P=0.079). Energy percentage of protein in breakfast correlated with serum
calprotectin (P=0.008) and tended to correlate with serum zonulin (P=0.059).
Calprotectin in serum tended to be elevated, and zonulin in serum and feces are
elevated after introduction of an Okinawan-based Nordic diet. These biomarkers
correlate with energy percentage of protein.
PMID- 28413640
TI - Clinicopathological examination of dipeptidase 1 expression in colorectal cancer.
AB - Dipeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is fundamental
in glutathione and leukotriene metabolism. DPEP1 was initially considered as a
tumor suppressor gene in Wilms' tumor and breast cancer. However, it has been
reported that DPEP1 is upregulated in colorectal cancers (CRCs) and high DPEP1
expression levels are associated with poorer patient survival. The role of DPEP1
genes in CRC, as well as their expression, requires investigation. Therefore, the
present study investigated DPEP1 expression using reverse transcription
quantitative polymerase chain reaction or immunohistochemistry on surgically
resected samples from CRC cases, and further examined the biological significance
of DPEP1 by comparing the expression of the epithelial to mesenchymal transition
(EMT) markers, including epithelial cadherin and Vimentin to clarify the function
of DPEP1 in CRC, particularly in metastasis. The level of DPEP1 expression was
identified to be significantly increased in tumorous tissue samples compared with
that in non-tumorous tissue samples. In addition, increased DPEP1 mRNA expression
levels were associated with positive lymph node metastasis in the included
cohort. However, no positive correlations were observed between DPEP1 and EMT
markers in the cohort. The results indiciates that further investigations into
the upregulation of DPEP1 in colorectal carcinogenesis and the role of
therapeutic or prognostic biomarkers are required.
PMID- 28413641
TI - Serum miR-20a is a promising biomarker for gastric cancer.
AB - Gastric cancer (GC) is a common type of cancer, particularly in China. Numerous
studies have demonstrated that circulating microRNAs (miRNAs) have potential
applications as noninvasive biomarkers for cancer diagnosis and prognosis.
Microarray-based serum miRNA profiling was performed on the serum of 12 paired
pre- and post-operative GC patients to screen differentially expressed serum
miRNAs. Twelve different serum miRNAs between pre- and post-operative GC patients
were identified. Those miRNAs were verified by real-time quantitative polymerase
chain reaction in 110 paired pre- and post-operative serum samples from 55 GC
patients. miR-20a was confirmed and demonstrated potential as a GC-associated
biomarker. Furthermore, the levels of serum miR-20a were significantly different
between GC, nasopharyngeal cancer, colorectal carcinoma, breast cancer and non
cancerous controls. In addition, it was found that serum miR-20a levels
correlated with age, tumor stage, differentiated degree and lymph node metastasis
in GC. Survival analysis indicated that GC patients with elevated levels of serum
miR-20a had poor survival. Thus, serum miR-20a may serve as a molecular marker
for diagnosis, evaluating therapeutic efficacy and prognosis, as well as
monitoring recurrence in GC patients.
PMID- 28413642
TI - Ginsenoside Rd as a potential neuroprotective agent prevents trimethyltin injury.
AB - Trimethyltin (TMT) is a potent neurotoxicant that affects various regions within
the central nervous system, including the neocortex, cerebellum, and hippocampus.
In the present study, ginsenoside Rd was investigated as a candidate
neuroprotective agent in a primary hippocampal neuron culture and mouse models.
TMT induced neurotoxicity in a seven-day primary hippocampal neuron culture in a
dose-dependent manner (2.5-10 uM). However, pre-treatment with 20 ug/ml
ginsenoside Rd for 24 h reversed the toxic action. ICR mice were administered a
single injection of 2 mg/kg body weight TMT. Apparent tremor seizure and impaired
passive avoidance tests demonstrated significant differences when compared with a
saline treated control group. Nissl staining was performed to evaluate the
neuronal loss in the hippocampus. In addition, immunostaining of glial fibrillary
acidic protein characterized the features of astroglial activation. These results
demonstrated that TMT markedly induced Cornu Ammonis 1 subregion neuronal loss
and reactive astrocytes in the hippocampus, indicating disrupted hippocampal
function. Notably, ginsenoside Rd attenuated the tremor seizures and cognitive
decline in behavioral tests. Additionally, significantly reduced neuronal loss
(P=0.018) and active astroglials (P=0.003) were observed in the ginsenoside Rd
treated group. Ginsenoside Rd prevented TMT-induced cell apoptosis via regulation
of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 and caspase-3. These results
demonstrate that ginsenoside may be developed as a neuroprotective agent to
prevent TMT-induced neurotoxicity.
PMID- 28413643
TI - Cytotoxic and antimigratory effects of Cratoxy formosum extract against HepG2
liver cancer cells.
AB - The aim of the present study was to investigate the molecular mechanisms
underlying Cratoxylum formosum (CF) Dyer-induced cancer cell death and
antimigratory effects in HepG2 liver cancer cells. The cytotoxic,
antiproliferative and antimigratory effects of CF leaf extract on human liver
cancer HepG2 cell lines were evaluated using sulforhodamine B, colony formation,
and wound healing assays. In addition, apoptosis induction mechanisms were
investigated via reactive oxygen species (ROS) formation, caspase 3 activities,
and mitochondrial membrane potential (DeltaPsim) disruption. Gene expression and
apoptosis-associated protein levels were measured by reverse transcription
quantitative polymerase chain reaction and western blotting. CF induced HepG2
cell death in a time- and dose-dependent manner with half maximal inhibitory
concentration values of 219.03+/-9.96 and 124.90+/-6.86 ug/ml at 24 and 48 h,
respectively. Treatment with CF caused a significant and dose-dependent decrease
in colony forming ability and cell migration. Furthermore, the present study
demonstrated that CF induced ROS formation, increased caspase 3 activities,
decreased the DeltaPsim, and caused HepG2 apoptosis. CF marginally decreased the
expression level of the cell cycle regulatory protein, ras-related C3 botulinum
toxin substrate 1 (rho family, small GTP binding protein Rac1) and the downstream
protein, cyclin dependent kinase 6. Additionally, CF significantly enhanced p21
levels, reduced cyclin D1 protein levels and triggered cancer cell death. CF leaf
extracts induced cell death, stimulated apoptosis and inhibited migration in
HepG2 cells. Thus, CF may be useful for developing an anticancer drug candidate
for the treatment of liver cancer.
PMID- 28413644
TI - Reduction in miRNA-125b-5p levels is associated with obstructive renal injury.
AB - Obstructive renal injury is a common disease that leads to progressive
glomerulosclerosis, tubulointerstitial fibrosis and loss of renal function.
MicroRNAs (miRNAs/miRs) are small non-coding molecules that may be involved in
the progression of many renal diseases. The aim of the present study was to
investigate the roles of miRNAs, including miR-125b, miR-326 and miR-324p, in
obstructive renal injury. Blood samples were collected from 91 patients with
ureteral obstruction and 76 controls to examine renal function. In addition, the
levels of miR-125b, miR-326 and miR-324p in patients with ureteral obstruction
and controls were determined by the reverse transcription-quantitative polymerase
chain reaction. Furthermore, the relationship between miRNA levels and renal
function was evaluated by the Mann-Whitney U test. Upregulated levels of serum
creatinine (SCr) in patients with ureteral obstruction were observed, identifying
the injury of renal function. Although the expression levels of miR-324-5p [1.003
(0.391-2.279) vs. 0.934 (0.579-1.539), P=0.300] and miR-326 [0.840 (0.180-2.020)
vs. 0.949 (0.507-1.702), P=0.050] presented no significant difference, the levels
of miR-125b-5p [0.755 (0.210-2.110) vs. 0.960 (0.390-1.770), P=0.002] in patients
with ureteral obstruction were significantly lower than those in controls. These
results indicated that there is a stronger correlation of miR-125b-5p with the
occurrence of ureteral obstruction, especially for the female (P=0.0171) and
elderly (P=0.0142). Furthermore, the levels of miR-125b-5p (r=-0.175, P=0.038)
were closely associated with the serum levels of SCr, suggesting a key role of
miR-125b-5p in renal dysfunction. Thus, these findings suggested that miR-125b-5p
in patients with ureteral obstruction correlated with renal function, and may be
a potential biomarker for obstructive renal injury.
PMID- 28413645
TI - Long non-coding RNA CCAT1 is overexpressed in oral squamous cell carcinomas and
predicts poor prognosis.
AB - Oral squamous cell carcinoma (SCC) is the most common malignant tumor in India
with 5-year survival rates totaling <50%. Recently, dysregulation of non-coding
RNA was reported as a potential hallmark of carcinogenesis. Colon Cancer
Associated Transcript 1 (CCAT1), an lncRNA located in chromosome 8q24, close to
the c-Myc gene, has been reported to be overexpressed in many human cancers. In
the present study, the authors analyzed the expression of CCAT1, c-Myc and the
miRNAs miR155-5p, let7b-5p, miR490-3p and miR218-5p sponged by CCAT1 in 60 oral
tumor and 8 normal tissue samples by reverse transcription-quantitative
polymerase chain reaction. CCAT1 was significantly overexpressed in 27% (16/60)
of oral tumors. Interestingly, a high level of c-Myc expression was observed in
all CCAT1 overexpressing cases (P=0.0473). Furthermore, CCAT1 overexpression
significantly downregulated miR155-5p (P=0.03) and let7b-5p (P<0.0001). Oral
cancer cases expressing high level of CCAT1 (P=0.01) presented poor therapeutic
outcome. To the best of the authors' knowledge, this is the first study to report
the overexpression of the CCAT1 in oral SCCs, and the results suggested that
CCAT1 overexpression may sponge miR155-5p and let7b-5p, and may account for poor
treatment response.
PMID- 28413646
TI - Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the
glycolysis pathway in tumors.
AB - High aerobic glycolysis, as one of the hallmarks of cancer cells, requires
nicotinamide adenine dinucleotide (NAD+) as a vital co-factor, to guarantee the
flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer
metabolism, is a source of NAD+ additional to lactate dehydrogenase (LDH). The
current study aimed to elucidate the kinetic parameters of MDH in human breast
cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis
Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the
crude extracts of human breast tumors and healthy tissue samples, which were
obtained directly from the operating theatre. To assess the potential role of MDH
in supporting glycolysis, the MDH activity was measured when the LDH activity was
inhibited by different concentrations of oxamate, an inhibitor of LDH in breast
cancer cell lines. The Km of cancerous MDH (C-MDH) was the same as the healthy
MDH, although the Vmax of C-MDH was higher relative to the healthy MDH. Notably,
the MDH activity was increased in the MDA-MB-231 cell line, which was treated
with the LDH inhibitor (oxamate), but not in the MCF-7 cell line (P<0.05). The
higher tendency of C-MDH for NAD+ and malate generation in cancer cells is an
effective approach for supporting glycolysis. Increasing MDH activity in the
absence of LDH demonstrates the supportive role of MDH in glycolysis. Therefore,
decreasing MDH activity and expression in a forward reaction may present as a
valid molecular target to abolish its potential effect on tumor metabolism.
PMID- 28413647
TI - Nigella sativa seed extract attenuates the fatigue induced by exhaustive swimming
in rats.
AB - In previous studies, Nigella sativa (NS) has been studied due to its various
physiological and pharmacological activities. However, evidence on the effects of
NS on physical fatigue following exhaustive swimming remains limited. In the
present study, the authors evaluated the potential beneficial effects of NS
against the fatigue activity following exhaustive swimming. Rats were orally
administered with NS extract (2 g/kg/day) for 21 days, and the anti-fatigue
effect was assessed by exhaustive swimming exercise. The presented results
indicated that pre-treatment of NS extract significantly increased the time to
exhaustion. In hemodynamic parameters, NS extract increased blood pO2 and O2sat,
but decreased pCO2. For underlying mechanisms, NS extract protected depletion of
energy, indicated by increased levels of blood pH, glucose and tissue glycogen
contents, and decreased levels of blood lactate, tissue lactic dehydrogenase and
creatine kinase, when the NS extract was pre-treated. In addition, the NS extract
inhibited oxidative stress following exhaustive swimming, as reflected by the
results of increased levels of superoxide dismutase and redox ratio, and
decreased the level of malondialdehyde when the NS extract was pre-treated.
Collectively, the present study demonstrated that NS extract has an anti-fatigue
activity against exhaustive swimming by energy restoration and oxidative-stress
defense.
PMID- 28413648
TI - Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901.
AB - Hyperbaric oxygen (HBO) has been previously identified as an effective adjunct
treatment option for the management of brain injury, diabetic ulcers and chronic
wounds. However, the roles of HBO as an adjunctive therapy for tumors remain
controversial. The present research project was performed to explore the effects
of HBO treatment on proliferation, autophagy and endoplasmic reticulum stress
response of the gastric cancer cell line, SGC7901. The present study demonstrated
that, after subjecting SGC7901 cells to HBO treatment, the increase in cell
proliferation was significant, compared with that of the control group. In
addition, there was a significant increase in LC3-phosphatidylethanolamine
conjugate (LC3-II) level, as well as binding immunoglobulin protein level, and a
significant decrease in CCAAT-enhancer-binding protein homologous protein level.
These suggested that hyperbaric oxygen treatment alone may promote proliferation
and cell survival of gastric cancer cell SGC7901, and inhibit apoptosis through
regulating cell autophagy and oxidative stress.
PMID- 28413649
TI - Hazardous factors besides infection in hypoglycemia.
AB - Hypoglycemia is one of the most common issues encountered in daily emergency
practice. In addition to the treatment of hypoglycemia, certain other situations
concomitant with hypoglycemia require further treatment. The aim of the present
study was to compare demographic and clinical characteristics of infected
[urinary tract infection (UTI), pneumonia or biliary tract infection (BTI)] vs.
non-infected hypoglycemic patients to establish which hypoglycemic patients
required further observation or hospitalization. This was a retrospective cross
sectional study of hypoglycemic (<60 mg/dl) hospitalized patients. The patients
were divided into two groups: Those with hypoglycemia and concurrent infection
(UTIs, pneumonia or BTIs; n=103) and non-infected hypoglycemic patients (n=83).
Student's t-test was performed to analyze continuous data and the chi2 test was
used to analyze categorical data. Infections included 62 UTI, 43 pneumonia and 5
BTI. Comparing between the infected and non-infected groups, no significant
differences were identified between mean glucose or body temperature, concurrent
diagnosis (liver cirrhosis, uremia, acute renal failure, stroke or cancer) or
mortality rate. Compared with the non-infected subjects, the infected patients
were significantly older and had a significantly higher female ratio, as well as
increased heart rates, white blood cell count and C-reactive protein levels. The
present study proposes that characteristics, including concurrent stroke, liver
cirrhosis and cancer are a point of focus in the initial management of
hospitalized hypoglycemic patients.
PMID- 28413650
TI - Clinical features of hemodialysis patients treated for hepatocellular carcinoma:
Comparison between resection and radiofrequency ablation.
AB - There is no consensus regarding which therapeutic option is better and/or safer
for treating hemodialysis (HD) patients with hepatocellular carcinoma (HCC). The
present study compared surgical resection (Hx) and radiofrequency ablation (RFA)
with regard to therapeutic efficacy in HD patients with HCC. Of 108 HD patients
with naive HCC treated at 15 institutions between 1988 and 2014 enrolled in the
present study, 58 fulfilled the up-to-7 criteria [7 as the sum of the size of the
largest tumor (cm) and the number of tumors] and were treated with Hx (n=23) or
RFA (n=35); their clinical features, complications and prognosis were assessed.
The frequency of hepatitis C virus was higher in the RFA group compared with that
in the Hx group (P=0.002), whereas there were no differences between the groups
with regard to the average time from the first HD (P=0.953), tumor-nodes
metastasis (TNM) stage (Union for International Cancer Control 7th edition)
(P=0.588), TNM stage (Liver Cancer Study Group of Japan 5th edition) (P=0.095),
Child-Pugh classification (P=0.094), and Japan Integrated Scoring system
(P=0.489). There were no significant differences in overall survival (OS) and
disease-free survival (DFS) rates between the Hx and RFA groups [1-, 3- and 5
year OS rates: 81.7, 55.6 and 43.3% vs. 89.9, 67.1 and 56.3%, respectively
(P=0.454); 1-, 3- and 5-year DFS rates: 71.1, 30.5 and 18.3% vs. 63.8, 31.6 and
21.1%, respectively (P=0.911)] Complications were observed in 4 patients (11.4%)
in the RFA group (2 with subcapsular hemorrhage, 1 with intraperitoneal bleeding
and 1 with tardive intrahepatic hematoma) and in 4 patients (17.4%) in the Hx
group (2 with postoperative infection, 1 with liver failure and 1 with pleural
effusion) (P=0.700). In conclusion, Hx and RFA have a similar therapeutic
efficacy in HD patients with naive HCC who fulfilled the up-to-7 criteria.
PMID- 28413652
TI - Bilateral blindness with secondary retinitis pigmentosa following postoperative
docetaxel and platinum combination chemotherapy in primary small-cell carcinoma
of the endometrium: An unusual case report and review of the literature.
AB - Ocular toxicity is an uncommon complication of cytotoxic chemotherapy. Bilateral
blindness with secondary retinitis pigmentosa (RP) following docetaxel and
platinum combination chemotherapy at the recommended dose is extremely rare. The
present study reports a case of advanced small-cell carcinoma (SCC) of the
endometrium in a patient with diabetes mellitus type 2. The patient suffered from
RP with a sharp decline in vision after the fourth course of postoperative
docetaxel and platinum combination chemotherapy. Unfortunately, the patient
developed bilateral blindness after another course of chemotherapy at a reduced
dose. No tumor recurrence was observed during the 33 months of follow-up. A total
of 35 cases of docetaxel- and/or platinum-induced retinal toxicity were found in
the English literature and reviewed. The ischemic and electrophysiological
hypotheses may have been implicated in the pathogenesis of ocular toxicity in the
present case, particularly with the history of diabetes. Understanding the ocular
side effects of this combination chemotherapy may assist gynecological
oncologists and ophthalmologists with early recognition and timely intervention
before blindness is established.
PMID- 28413651
TI - High radiofrequency radiation at Stockholm Old Town: An exposimeter study
including the Royal Castle, Supreme Court, three major squares and the Swedish
Parliament.
AB - Exposure to radiofrequency (RF) radiation was classified as a possible human
carcinogen, Group 2B, by the International Agency for Research on Cancer at WHO
in 2011. The exposure pattern is changing due to the rapid development of
technology. Outdoor RF radiation level was measured during five tours in
Stockholm Old Town in April, 2016 using the EME Spy 200 exposimeter with 20
predefined frequencies. The results were based on 10,437 samples in total. The
mean level of the total RF radiation was 4,293 uW/m2 (0.4293 uW/cm2). The highest
mean levels were obtained for global system for mobile communications (GSM) +
universal mobile telecommunications system (UMTS) 900 downlink and long-term
evolution (LTE) 2600 downlink (1,558 and 1,265 uW/m2, respectively). The town
squares displayed highest total mean levels, with the example of Jarntorget
square with 24,277 uW/m2 (min 257, max 173,302 uW/m2). These results were in
large contrast to areas with lowest total exposure, such as the Supreme Court,
with a mean level of 404 uW/m2 (min 20.4, max 4,088 uW/m2). In addition,
measurements in the streets surrounding the Royal Castle were lower than the
total for the Old Town, with a mean of 756 uW/m2 (min 0.3, max 50,967 uW/m2). The
BioInitiative 2012 Report defined the scientific benchmark for possible health
risks as 30-60 uW/m2. Our results of outdoor RF radiation exposure at Stockholm
Old Town are significantly above that level. The mean exposure level at
Jarntorget square was 405-fold higher than 60 uW/m2. Our results were below the
reference level on 10,000,000 uW/m2 established by the International Commission
on Non-Ionizing Radiation Protection (ICNIRP), which, however, are less credible,
as they do not take non-thermal effects into consideration and are not based on
sound scientific evaluation. Our highest measured mean level at Jarntorget was
0.24% of the ICNIRP level. A number of studies have found adverse, non-thermal
(no measurable temperature increase) health effects far below the ICNIRP
guidelines.
PMID- 28413653
TI - A novel option for preoperative endoscopic marking with India ink in totally
laparoscopic distal gastrectomy for gastric cancer: A useful technique
considering the morphological characteristics of the stomach.
AB - In totally laparoscopic distal gastrectomy (TLDG) for gastric cancer, accurately
determining the proximal resection line may be difficult. This is because
identifying the lesion intracorporeally is impossible, due to the lack of tactile
sense, and, in addition, unlike the intestine, the most proximal site of the
lesion is often different from the main site due to the distorted shape of the
stomach. The aim of this study was to introduce a novel method of preoperative
endoscopic marking with India ink, taking into consideration the morphological
characteristics of the stomach. Between July, 2013 and April, 2016, 20 patients
who underwent TLDG were enrolled in this study. Within the 3 days preceding the
operation, after identifying the most proximal site of the lesion on the
overlooking image of an endoscope, India ink was injected into the spot on the
oral side of this site. The stomach was transected along the proximal border of
the marked area. In all cases, the marked sites were localized and clearly
identified during the operation, and the proximal resection margins were found to
be negative on postoperative pathological examination. The mean length of the
proximal margin was 46.0+/-14.0 mm. In conclusion, this preoperative endoscopic
marking method may be useful in TLDG for gastric cancer.
PMID- 28413654
TI - Hepatic perivascular epithelioid cell neoplasm: A clinical and pathological
experience in diagnosis and treatment.
AB - Hepatic perivascular epithelioid cell neoplasm (PEComa) is a rare type of
neoplasm derived from mesenchymal tumors that is often misdiagnosed as
hepatocellular carcinoma (HCC), hepatic hemangioma or other liver malignancies.
The clinical and histological characteristics of PEComa have yet to be fully
documented. To optimize the diagnosis and treatment of the disease, a
retrospective analysis was performed to investigate the clinicopathological
characteristics of 7 patients diagnosed with hepatic PEComa in the Sun Yat-Sen
Memorial Hospital between January 2004 and December 2015. Briefly, all the
patients lacked specific symptoms, and a serological examination provided no
further useful information. Additionally, non-specific imaging manifestations
were observed. Microscopically, detection of epithelioid or spindle-shaped cells
with adipocytes was suggestive of the disease, and an analysis of biomarkers,
including the monoclonal antibody HMB-45, the melanocytic differentiation marker,
Melan-A, and smooth muscle alpha-actin (SMA), helped to confirm the diagnosis.
Regarding the treatment, 6 patients (85.7%) received surgical resection
procedures, and 1 patient (14.3%) was admitted for tumor arterial embolization
and percutaneous microwave coagulation therapy. After a follow-up period of 12-20
months, no recurrence was observed. Taken together, hepatic PEComa should be
suspended in patients with a liver tumor with asymptomatic manifestation and
normal serological test results. In imaging studies, hepatic PEComa was able to
mimic HCC, hepatic hemangioma and metastatic tumor, although the mass did not
invade the adjacent organs and vessel. The definitive diagnosis was made on the
basis of the typical morphological features and notable markers of the tumor
tissue. It is recommended that patients with PEComa in a benign pattern deserve
serial imaging follow-up, but surgery is indicated in patients suffering from
large tumors (>5 cm), or progressive enlargement or malignant tendency.
PMID- 28413655
TI - Functional analysis of polymorphisms in the COX-2 gene and risk of lung cancer.
AB - The enzyme cyclooxygenase 2 (COX-2) is known to be involved in tumorigenesis and
metastasis in certain types of cancer. Nevertheless, the prognostic value of COX
2 overexpression and its polymorphisms in patients with non-small cell lung
cancer (NSCLC) have yet to be fully elucidated. The aim of the present study was
to investigate the association between the three most commonly studied COX-2 gene
polymorphisms (-1195 G/A, -765 G/C and 8473 T/C) with COX-2 expression and lung
cancer risk in a Brazilian cohort. In the present hospital based, case-control
retrospective study, 104 patients with NSCLC and 202 cancer free control subjects
were genotyped for -1195 G/A, -765 G/C and 8473 T/C polymorphisms using allelic
discrimination with a reverse transcription quantitative polymerase chain
reaction method. COX-2 mRNA expression was analyzed in surgically resected tumors
from 34 patients with NSCLC. The results revealed that COX-2 expression levels
were higher in tumor tissue compared with normal lung tissue. However, this
overexpression of COX-2 was not associated with the patient outcome, and
furthermore, none of the analyzed polymorphisms were associated with the risk of
developing lung cancer, COX-2 overexpression, or the overall survival of the
patients with NSCLC. Taken together, the findings described in the present study
do not support a major role for COX-2 polymorphisms and COX-2 overexpression in
lung carcinogenesis within the Brazilian population.
PMID- 28413656
TI - Effect of Ki-67 assessment in the distribution of breast cancer subtypes:
Evaluation in a cohort of Latin American patients.
AB - Breast cancer (BC) is a heterogeneous disease composed of four main subtypes with
distinct clinical and epidemiological features. Although several reports have
described the distribution of BC subtypes in Latin America, the majority of them
have not included the cellular marker, Ki-67, in the immunohistochemical (IHC)
panel. The aim of the present study was to describe the distribution of BC
subtypes in a cohort of Latin American women using an IHC panel with Ki-67. A
prospective cohort of 580 patients in three centers of Peru (the Hospital
Nacional Edgardo Rebagliatti Martins, the Hospital Nacional Guillermo Almenara
Irigoyen, the Hospital Nacional Alberto Sabogal, Lima) and one in Uruguay
(Instituto Nacional del Cancer, Montevideo) were evaluated. BC phenotypes were
classified according to an IHC panel: Estrogen receptor (ER), progesterone
receptor (PgR), HER2 and Ki-67. Silver in situ hybridization was used when the
HER2 status, as determined by IHC, was equivocal. The associations between the BC
phenotypes and their clinicopathological features were evaluated. ER was positive
in 65% of the cases (n=377), and PgR in 50% (n=203). In total, 79.1% (n=459) were
HER2-negative, 19.8% (n=115) were HER2-positive and 1% (n=6) had an equivocal
status. With respect to Ki-67, 44.7% of the patients exhibited staining in >14%
of the tumor cells (n=259). The distribution of subtypes was as follows: Luminal
A, 31.9% (n=183); luminal B, 35% (n=201); HER2, 12.1% (n=70); and triple
negative, 20.9% (n=120). When Ki-67 was not included in the panel, the frequency
of luminal A was 41.1% and luminal B, 25.8% (9.2% of the cases were
misclassified). Ki-67 was most highly expressed in triple-negative and HER2
tumors. Inclusion of Ki-67 in the IHC panel to assign subtypes revealed a higher
frequency of luminal B tumors than was reported previously for Latin American
women with BC, whereas the distribution of triple-negative and HER2 tumors were
similar to that previously reported. In conclusion, these results demonstrated
that excluding Ki-67 from the panel of IHC markers may lead to an underestimation
of the rates of luminal B tumors.
PMID- 28413657
TI - A feasibility study of bevacizumab and vinorelbine in patients with previously
treated advanced non-squamous non-small-cell lung cancer.
AB - The aim of this prospective study was to evaluate the efficacy and feasibility of
bevacizumab combined with vinorelbine therapy in patients with previously treated
non-squamous non-small-cell lung cancer (nonSq-NSCLC). Patients who had received
at least one prior chemotherapy course were eligible for this study. The patients
were treated with vinorelbine (25 mg/kg on days 1 and 8) and bevacizumab (15
mg/kg on day 1), which was repeated every 3 weeks until the development of
progressive disease or unacceptable toxicity. Between June, 2011 and January,
2013, 15 patients were enrolled. The response and disease control rates were 26.7
and 73.3%, respectively. The median progression-free survival was 2.1 months and
the median overall survival was 34.1 months. Grade 3-4 phlebitis occurred in 3
patients. Therefore, the combination of vinorelbine and bevacizumab was found to
be effective in patients with previously treated nonSq-NSCLC, but physicians must
be aware of the risk of phlebitis associated with this regimen.
PMID- 28413658
TI - Subcutaneous metastasis arising from gastric cancer: A case report.
AB - A 59-year-old man was referred to the Kochi Medical School Hospital due to left
shoulder pain. Physical examination revealed a nodular, painful mass lesion in
the subcutaneous tissue of the right chest wall, with a diameter of ~2 cm.
Esophagogastroduodenoscopy revealed a large ulcerated tumor in the lower gastric
body near the lesser curvature, and biopsy specimens of the gastric and humeral
lesions revealed poorly differentiated adenocarcinoma. Abdominal computed
tomography revealed multiple low-density lesions in the liver and a well-defined,
2.2-cm mass in the subcutaneous tissue of the right chest wall. The diagnosis was
advanced gastric cancer with metastases to the liver, bone and skin, and systemic
chemotherapy with radiotherapy for the bone metastasis was recommended. The
patient also underwent distal gastrectomy to control bleeding from the primary
gastric cancer lesion due to unresolved anemia, not improving by blood
transfusion, and a low hemoglobin level. The subcutaneous tumor in the right
chest wall was resected at the same time, to alleviate the pain caused by the
mass. Macroscopic examination of the resected specimen revealed a well
circumscribed, solid tumor, measuring 2.2*2.1 cm, with a firm consistency.
Microscopic examination showed infiltration of poorly differentiated
adenocarcinoma cells into the subcutaneous tissue. Subcutaneous metastasis from
gastric cancer is a rare manifestation, with a reported incidence of 0.8-1.0%.
Cutaneous metastasis of cancer generally appears late in the course of the
disease. Surgical resection of metastatic skin tumors is occasionally undertaken
as palliative treatment to improve the patient's quality of life by controlling
severe symptoms, including pain and hemorrhage.
PMID- 28413659
TI - Patient gender as a factor associated with lymph node metastasis in T1 colorectal
cancer: A systematic review and meta-analysis.
AB - Approximately 10% of patients with T1 colorectal cancer have lymph node
metastases (LNM), requiring node dissection along with surgical resection.
Patient gender was recently reported to affect the occurrence of LNM. The aim of
the present study was to assess whether patient gender was predictive of LNM in
T1 colorectal cancer. Public databases, including PubMed, EMBASE and the Cochrane
Central Register of Controlled Trials were searched, using key terms related to
'T1 colorectal cancer' and 'lymph node'. All relevant studies reporting the
adjusted odds ratio or risk ratio of LNM in relation to patient gender were
included. The quality of the studies was classified according to the Quality in
Prognostic Studies tool. A random-effects model was used and the quality of the
evidence was evaluated using the Grading of Recommendations Assessment,
Development and Evaluation approach. The initial database search identified 2,492
publications; of those, 36 studies reported unadjusted results. Of the 36
studies, 4 reported adjusted results and fulfilled the inclusion criteria for
this meta-analysis: 3 studies were graded as having a moderate risk of bias, and
1 had a low risk of bias. The present meta-analysis demonstrated that female
gender was associated with increased risk of LNM (risk ratio=2.45, 95% confidence
interval: 1.03-3.88). The I2 statistic was 0.901, classified as very low (+OOO)
and was downgraded by the risk of bias, inconsistency and publication bias. In
conclusion, female gender was found to be correlated with LNM in patients with T1
colorectal cancer.
PMID- 28413660
TI - Dramatic intracranial response to osimertinib in a poor performance status
patient with lung adenocarcinoma harboring the epidermal growth factor receptor
T790M mutation: A case report.
AB - We herein report a case of dramatic intracranial response to osimertinib in a
poor performance status patient with lung adenocarcinoma harboring the epidermal
growth factor receptor (EGFR) T790M mutation encoded in exon 20. The patient was
a 59-year-old woman with EGFR exon 19 deletion-positive lung adenocarcinoma, who
relapsed with multiple brain metastases. Computed tomography-guided biopsy of the
left pleural tumor revealed adenocarcinoma harboring an EGFR exon 19 deletion and
an EGFR T790M mutation encoded in exon 20. The patient was treated with
osimertinib, a third-generation EGFR tyrosine kinase inhibitor. Two days after
treatment initiation, the patient displayed profound disturbance of
consciousness, possibly due to carcinomatous meningitis, and treatment had to be
discontinued due to difficulty in taking osimertinib. However, the patient
gradually started to recover consciousness and, after 3 days, she was again able
to take osimertinib. One month after the initiation of osimertinib treatment,
magnetic resonance imaging revealed an apparent reduction in brain metastases.
The patient is currently under continued treatment with osimertinib. At the last
follow-up (February, 2017) she exhibited partial response to the treatment.
PMID- 28413661
TI - Non-alcoholic fatty liver disease fibrosis score predicts hematological toxicity
of chemotherapy including irinotecan for colorectal cancer.
AB - Liver dysfunction that may affect drug metabolism is a major concern in patients
treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is
crucial for predicting the adverse events of chemotherapy. The non-alcoholic
fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring
system constructed from routine clinical and laboratory variables. The aim of
this study was to evaluate whether NFS was useful for predicting the adverse
events of chemotherapy including irinotecan (CPT-11) for colorectal cancer.
Between January, 2007 and May, 2013, a total of 87 patients with
unresectable/recurrent colorectal cancer who received first-line chemotherapy
including CPT-11 were reviewed. Demographic variables, including pretreatment
NFS, were retrospectively collected from medical records. The primary outcome was
the association between pretreatment NFS and adverse events, such as
hematological and non-hematological toxicity, of chemotherapy including CPT-11.
The median pretreatment NFS was 1.302 (range, 5.158-2.620). Pretreatment NFS was
an independent risk factor for hematological toxicity in a multivariate analysis
(coefficient=0.932, 95% CI: 0.083-1.781; P=0.031). Receiver operating
characteristic curve analysis identified 0.347 as the optimal cut-off value
associated with hematological toxicity. Using this cut-off, high NFS was found to
be a significant risk factor for hematological toxicity (coefficient=2.019, 95%
CI: 0.239-3.798, P=0.026), but not for non-hematological toxicity (P=0.546).
Therefore, based on these results, NFS appears to be a significant predictor of
hematological adverse events in chemotherapy including CPT-11 for colorectal
cancer and it is a non-invasive, useful tool that may be used for determining
regimens or doses of chemotherapy including CPT-11.
PMID- 28413662
TI - Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and
trastuzumab in women with human epidermal growth factor receptor 2-overexpressing
breast cancer.
AB - Although the concurrent use of anthracycline-containing chemotherapy and taxane
with trastuzumab are considered the treatment of choice for the primary systemic
therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early
breast cancer, non-anthracycline regimens, such as concurrent administration of
docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a
previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound
paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a
favorable safety profile compared with standard paclitaxel for metastatic breast
cancer patients in another phase III study. Based on these results, a phase I
study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was
planned, in order to estimate its efficacy and safety for HER2-overexpressing
locally advanced breast cancer. The present study was designed to determine the
dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this
combination treatment in women with HER2-overexpressing locally advanced breast
cancer. The starting dose of nab-paclitaxel was 220 mg/m2 (level 1), and the dose
was escalated to 260 mg/m2 (level 2). Nab-paclitaxel was administered with
carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A
total of 6 patients were enrolled. Although no DLT was observed during the first
cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia
and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I
study, although no patients experienced DLTs, this regimen was associated with
severe hematological toxicities and it was not well tolerated. However,
considering the high efficacy and lower risk of cardiotoxicity and secondary
carcinogenesis with taxane, platinum and trastuzumab combination therapy, further
evaluation of another regimen including weekly administration or a more accurate
dose setting should be conducted.
PMID- 28413663
TI - Breast implant-associated anaplastic large-cell lymphoma and the role of
brentuximab vedotin (SGN-35) therapy: A case report and review of the literature.
AB - Breast implant-associated (BIA) anaplastic large-cell lymphoma (ALCL) is a rare
disease, comprising a small percentage of all non-Hodgkin lymphomas (NHLs),
reportedly 2-3%. There is currently no established standard approach to the
treatment of BIA ALCL. The first case on the development of ALCL in the presence
of a breast implant was reported in 1997 and the association was first identified
by the Food and Drug Administration in 2011. We herein describe a case of BIA
ALCL in a patient with a previous history of breast cancer and breast
reconstruction who presented with hardening of her breast implant. The patient
underwent capsulectomy and the findings of the pathological examination were
consistent with ALCL. The patient completed three cycles of combination
chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and
prednisone (CHOP regimen) followed by radiation consolidation therapy, and has
maintained a complete remission ever since. The aim of the present study was to
review the treatment options for BIA ALCL and suggest an investigation of the
CD30-directed antibody-drug conjugate, brentuximab vedotin, as a potential
treatment option for BIA ALCL.
PMID- 28413664
TI - Extranodal natural killer/T-cell lymphoma presenting as cavernous sinus syndrome.
AB - Extranodal natural killer (NK)/T-cell lymphomas are rare, highly aggressive
tumors of the central nervous system (CNS) that commonly affect the nasal cavity
or paranasal sinuses. NK/T-cell lymphomas are associated with a poor prognosis,
as they exhibit a wide range of unique clinical presentations and neuroimaging
findings that are currently difficult to detect. Pathological examination is
considered to be more reliable for defining the pathological entity of NK/T-cell
lymphoma. Early testing for fluorodeoxyglucose (FDG)-positron emission tomography
combined with computed tomography may improve the evaluation of lymphomas, which
have been known to display avid 18FDG uptake. The authors herein report a case of
NK/T-cell lymphoma presenting with cavernous sinus syndrome involving the CNS via
direct extension from the nose. NK/T-cell lymphomas are very aggressive, with an
unfavorable clinical outcome, and the optimal therapy has not yet been clearly
defined.
PMID- 28413665
TI - Hepatic inflammatory pseudotumour-like follicular dendritic cell tumor: A case
report.
AB - Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) tumor
is a rare neoplasm. We herein report the case of 19-year-old female patient with
an IPT-like FDC tumor and summarize 24 cases of hepatic FDC tumors previously
reported in the English literature. The patient presented with complaints of
abdominal discomfort, without significant laboratory abnormalities, and underwent
surgical removal of a hepatic tumor. The resected tumor was 6 cm in the longest
diameter and the tumor cells were positive for CD21, CD35 and Epstein-Barr virus
(EBV). The postoperative course was uneventful and there have been no metastases
or recurrence during 1 year of follow-up. The majority of the cases of hepatic
IPT-like FDC tumors have a female predominance and exhibit an association with
EBV infection. Their clinical manifestations and image findings are usually non
specific and the diagnosis of this disease mainly relies on pathology.
PMID- 28413666
TI - Renal cell carcinoma presenting as a simple renal cyst: A case report.
AB - Cases of renal cell carcinoma (RCC) presenting as a simple cyst are extremely
rare. We herein report the case of a patient with RCC diagnosed as a simple renal
cyst preoperatively. A 39-year-old female patient presented with abdominal pain
for 3 months. Ultrasonography and contrast-enhanced computed tomography revealed
a simple cyst in the left kidney. The patient underwent laparoscopic
decortication of the renal cyst. Biochemical analysis of the cystic fluid
revealed unusually low levels of potassium, sodium, calcium and glucose, and the
histological examination of the floor of the cyst indicated malignancy.
Laparoscopic nephrectomy was performed 20 days later and the pathological
examination confirmed the diagnosis of RCC of the clear cell type. At the 2-year
follow-up, the patient remained well and recurrence-free on imaging. The aim of
the present study was to emphasize the importance of recognizing that RCC may
occur in what appears to be a simple renal cyst based on imaging results.
Biochemical analysis of the cystic fluid may help identify the presence of
malignancy.
PMID- 28413667
TI - Paraganglioma of the bladder in a kidney transplant recipient: A case report.
AB - Renal transplantation has been associated with a significantly increased risk of
developing cancer, including bladder neoplasia, with urothelial carcinoma being
the most frequent type of bladder cancer. Bladder paraganglioma, also referred to
as extra-adrenal pheochromocytoma, is a rare but severe condition that may cause
a severe hypertensive crisis during handling and mobilization of the tumor. We
herein present the case of a 67-year-old kidney transplant recipient with a
bladder polyp consistent with paraganglioma of the bladder. During bladder polyp
resection, the patient developed severe hypertension, which resolved with
appropriate treatment. The histological analysis of the resected bladder polyp
was consistent with extra-adrenal pheochromocytoma, or paraganglioma, and the
patient finally underwent partial cystectomy, with no reported postoperative
recurrence. To the best of our knowledge, this is the first report of a case of
paraganglioma of the bladder in a kidney tranplant recipient. Total or partial
bladder cystectomy is considered to be an effective treatment for this type of
bladder tumor. Screening for mutations of the succinate dehydrogenase subunit B
gene may also be recommended.
PMID- 28413668
TI - PALB2 mutation in a woman with bilateral breast cancer: A case report.
AB - Partner and localizer of breast cancer 2 (PALB2) was identified as a moderate
risk gene of breast and pancreas cancer. The present authors previously reported
that no PALB2 germline mutations with a deleterious frameshift or stop codons
were identified in 155 Japanese patients with breast and/or ovarian cancer who
were estimated to be at risk of hereditary cancer, according to the National
Comprehensive Cancer Network (NCCN) criteria. In the present study, one patient
with a deleterious mutation of PALB2 (c. 2834+2 T>C) has been identified from a
study of an additional 128 cases. Therefore, the prevalence of PALB2 among
Japanese patients is now estimated to be 0.35% (1/283). The proband was a 63-year
old woman with bilateral breast cancer, although she had experienced no other
cancers. The proband had two elder sisters, the eldest of whom died from
pancreatic cancer at 60 years of age. The proband's 40-year-old daughter was
affected, but did not show any malignancies. There are only a few reports
concerning PALB2 mutations in Japan. To the best of our knowledge, this is the
first case study to reveal the significance of DNA-repair genes in the
development of malignancies in Japanese patients with breast cancer.
PMID- 28413669
TI - Gemcitabine-based chemotherapy in colon squamous cell carcinoma: A case report
and literature review.
AB - Squamous cell carcinoma (SCC) originating from the colon is rare. In terms of its
clinicopathological characteristics, this type of cancer has been reported to be
more aggressive and have a worse prognosis compared with adenocarcinoma. We
herein present a successful therapeutic approach applying neoadjuvant and
adjuvant gemcitabine-based chemotherapy in a patient with colon SCC. A 58-year
old male patient received two cycles of neoadjuvant chemotherapy with a regimen
including gemcitabine, oxaliplatin and capecitabine, followed by radical excision
and six cycles of adjuvant chemotherapy. Contrast-enhanced computed tomography
and serum tumor markers were used for reassessment and evaluation was based on
the World Health Organization criteria. Following neoadjuvant chemotherapy, the
mass had shrunk and the patient was classed as having stable disease. Surgery and
adjuvant chemotherapy were then performed and the patient had achieved a
progression-free survival of 10 months when this report was submitted. Therefore,
gemcitabine may be a treatment option for colon SCC in the neoadjuvant and/or
adjuvant chemotherapy setting.
PMID- 28413670
TI - Glasgow Prognostic Score predicts prognosis of intrahepatic cholangiocarcinoma.
AB - High Glasgow Prognostic Score (GPS) has been associated with poor prognosis in
patients with lung, ovarian, colorectal and renal cancer, as well as
hepatocellular carcinoma. The aim of this study was to investigate the prognostic
value of GPS in patients with intrahepatic cholangiocarcinoma (ICC) undergoing
partial hepatectomy. A total of 72 patients with pathologically confirmed ICC
were classified according to their GPS scores assigned based on the preoperative
levels of C-reactive protein (CRP) and albumin. Their clinicopathological data
were retrospectively assessed using univariate and multivariate analysis to
determine their association with overall survival and recurrence. High GPS scores
in ICC patients were associated with preoperative levels of CRP (P<0.001) and
albumin (P<0.001), frequency of ascites accumulation (P=0.035), lymph node
metastasis (P=0.002) and tumour size (P=0.005). On univariate analysis,
preoperative levels of CRP (P<0.001), albumin (P=0.016) and carbohydrate antigen
19-9 (P=0.038), hepatitis B virus (HBV) positivity (P=0.009), occurrence of lymph
node metastasis (P=0.001), Child-Pugh class B (P=0.013) and high tumour-node
metastasis (TNM) stage (P=0.002) were found to be associated with the 1- and 3
year overall survival. Multivariate analysis suggested that GPS score (HR=2.037,
95% CI: 1.092-3.799, P=0.025), TNM classification (HR=2.000, 95% CI: 1.188-3.367,
P=0.009) and HBV positivity (HR=0.559 95% CI: 0.328-0.953, P=0.032) were
independently associated with patient survival. High GPS scores also predicted
ICC recurrence. In conclusion, our results demonstrated that GPS may serve as an
independent marker of prognosis in patients with ICC following partial
hepatectomy.
PMID- 28413671
TI - Paraneoplastic limbic encephalitis in a patient with extensive disease small-cell
lung cancer.
AB - Paraneoplastic limbic encephalitis (PLE) is a rare disorder infrequently
accompanying malignancy, coexisting in ~50% of the cases with small-cell lung
cancer (SCLC). The pathomechanism of PLE is considered to be immune-mediated,
with production of specific anti-Hu antibodies and activation of T-cells directed
against onconeural antigens present on both tumor cells and neurons. We herein
report the case of a 50-year-old male patient who, prior to being diagnosed with
SCLC, presented with typical symptoms of PLE (seizures, subacute cognitive
dysfunction with severe memory impairment, anxiety and hallucinations). The
initial brain magnetic resonance imaging examination revealed mild enlargement
and hyperintensity of the hippocampal gyri bilaterally, with narrowed temporal
horns of the lateral ventricles; the findings of the cerebrospinal fluid
examination were compatible with the diagnosis of lymphocytic meningitis. Due to
the suspected infectious origin of the disease, treatment with acyclovir and
antibiotics was initially applied. However, following subsequent diagnosis of the
underlying SCLC and the presence of antineuronal anti-Hu antibodies in the
patient's serum, the diagnosis of PLE accompanying extensive-disease (ED) SCLC
was confirmed. In addition to the standard cytotoxic therapy, throughout the
course of his disease the patient also continued treatment with valproic acid
(VPA) as prophylaxis for the initial seizures. VPA is known to be a potent
histone deacetylase inhibitor that may reverse epigenetic changes in tumor cells
and potentially improve the outcome of cancer patients. The patient succumbed to
the disease 25 months after the diagnosis of malignancy; such a long course is
observed in only ~5% of patients with ED SCLC. Therefore, it was hypothesized
that the accompanying paraneoplasia and treatment with VPA may have improved the
outcome in this patient.
PMID- 28413672
TI - Whole-body magnetic resonance imaging in the diagnosis and follow-up of
multicentric infantile myofibromatosis: A case report.
AB - Myofibromatosis is an uncommon disorder of infancy, characterized by
proliferation of myofibroblasts in solitary or multiple nodules. The clinical
characteristics depend on the involved sites: Myofibromatosis may develop as a
musculoskeletal form, with non-painful swellings and eventual mass effect
symptoms, or as a generalized form with visceral involvement and organ failure.
Prognosis and therapy vary between the abovementioned patterns. When there is no
visceral involvement, the tumors may regress spontaneously; however, the visceral
form may represent a lifethreatening condition with poor outcome and it requires
aggressive management. Imaging assessment of disease spread is mandatory to
determine diagnosis, prognosis and therapy. Due to the young age of the patients,
a radiation-free evaluation is recommended. We herein describe a case of
musculoskeletal myofibromatosis diagnosed in a 3-month-old male infant,
investigated by serial wholebody magnetic resonance imaging (MRI) examination.
The histological analysis and MRI characteristics enabled a correct diagnosis and
organ involvement assessment with no radiation exposure. Moreover, whole-body MRI
sequences provided a detailed evaluation of the disease within a short time
frame, reducing the time of sedation, which is required to perform MRI in very
young patients. Therefore, whole-body MRI was found to be accurate and safe in
the diagnosis and follow-up of multicentric infantile myofibromatosis.
PMID- 28413673
TI - Survival of patients with pancreatic cancer treated with varied modalities: A
single-centre study.
AB - The present retrospective chart review examined the overall survival (OS) of
patients with pancreatic ductal adenocarcinoma based on the disease stage in a
sample of 296 patients with pancreatic cancer. Secondary outcome measurements
included OS in chemotherapy vs. supportive treatment groups among metastatic
patients, OS based on response to chemotherapy among metastatic patients, and OS
and disease free survival (DFS) in surgically resected disease with vs. without
adjuvant therapy. Data were analyzed using Kaplan-Meier and multivariate cox
regression analyses based on a 95% confidence interval (CI) or an alpha-value of
0.05. OS was significantly different based on the disease stage, with 3.63 (95%
CI, 2.84-4.43), 6.57 (95% CI, 4.06-9.08) and 15.57 (95% CI, 11.79-19.35) months
in the advanced, locally advanced, and localized disease groups, respectively. OS
was higher in metastatic-stage patients who received chemotherapy [6.07 months
(95% CI, 4.75-7.39)] compared with those who received supportive therapy alone
[2.50 months (95% CI, 2.16-2.84; P<.001)]. Metastatic-stage patients with partial
or stable response to chemotherapy had higher OS [10.53 months (95% CI, 6.35
14.72)] in comparison with those with progression [6.33 months (95% CI, 5.79
6.88)] or an undocumented response [3.30 months (95% CI, 1.76-4.84; P<0.001)]. In
patients who underwent surgical resection of localized disease, adjuvant therapy
increased the adjusted OS and DFS as compared with surgical excision alone
(P=0.013; 95% CI, 0.278-0.862). Positive margins reduced OS [hazard ratio (HR)
2.670; 95% CI, 1.467-4.860]. The present single-site study has demonstrated that
OS may markedly differ on the basis of the disease status at the time of
diagnosis. Metastatic-stage patients with stable or partial response to
chemotherapy had an increased OS, as did surgical patients with localized disease
who received adjuvant treatment, after adjusting for margin status.
PMID- 28413674
TI - Spontaneous tumor lysis syndrome in a patient with metastatic prostate cancer.
AB - Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, with most
cases occurring in hematological malignancies following the initiation of
treatment. However, on rare occasions, TLS may occur in solid tumors as well. In
the present case study, the case is reported of a 56-year-old African-American
man who presented with a recent diagnosis of prostate cancer, abdominal pain,
elevated transaminases, renal insufficiency, hyperkalemia, and hyperuricemia,
consistent with spontaneous TLS in the setting of metastatic prostate cancer. A
computed tomography scan of the patient's abdomen demonstrated diffuse metastatic
tumor burden. Following treatment with allopurinol, rasburicase, and initiation
of anti-androgen therapy for the prostate cancer, the patient's TLS laboratory
results normalized, however, his renal functions continued to decline. TLS is
rare in solid tumors, and particularly rare in prostate cancer, with only six
other case reports of the syndrome occurring to the best of our knowledge. This
case report highlights the need for early recognition of TLS, even in cases that
are not typically associated with the syndrome, as prompt diagnosis will affect
early management and may be able to prevent or minimize complications.
PMID- 28413675
TI - Primary mesenteric adenocarcinoma covered by abscess of the mesocolon and
intestinal obstruction: A case report.
AB - Primary mesenteric adenocarcinoma (PMA) is a rare malignant disease. A case of
PMA that was covered by an abscess of the mesocolon and intestinal obstruction is
reported in the present study. As the onset site of PMA is often obscured or
hidden, there may be no clinical symptoms in the early stage. At the advanced
stage, the tumor size is large enough to induce intestinal obstruction,
perforation, bleeding, volvulus and other clinical symptoms in the majority of
patients. Computed tomography scans, ultrasound and other auxiliary examinations
are not sufficiently accurate for diagnosing PMA with non-specific
characteristics in the majority of cases, causing certain difficulties in the pre
operative diagnosis of PMA, which easily lead to misdiagnosis. The main effective
treatment of PMA is surgical resection as early as possible. Thus, when a patient
is suspected of having malignancies, and gastrointestinal cancer and other
malignancies of the digestive organs may be excluded, the possibility of PMA
should be considered.
PMID- 28413676
TI - Expression patterns of CD168 correlate with the stage and grade of squamous cell
carcinoma of head and neck.
AB - The receptor for hyaluronan-mediated motility CD168 is associated with the
processes of oncogenesis and metastasis. The objective of the present study was
to determine the possible association between the expression and distribution of
CD168 and the tumor stage of head-and-neck squamous cell carcinoma (SCC).
Formalin-fixed and paraffin-embedded tumor samples obtained from 100 patients
during primary resection of SCC from the oral cavity, oropharynx, hypopharynx or
larynx were included in the present study. The patients were divided into two
risk groups: Low risk, representing the early stage of completely resected SCCs
with good-to-moderate differentiation, and the high-risk group, representing the
advanced stage SCCs with positive resection margins, vascular invasion or
locoregional metastasis. All specimens were stained with a monoclonal antibody
against CD168. Percentage and staining intensity of CD168-positive cells were
scored, and their spatial distribution within the tumor nests was noted. The
results obtained were correlated with the tumor stage. The quantification of
CD168 expression revealed significant differences between the two risk groups (t
test, P=0.002), with higher scores in tumors resected from the high-risk SSC
group compared with those from the low-risk group. In addition, in the high-risk
group, the CD168-positive cells were present predominantly in the periphery
(70.4%) of tumor nests, whereas in the low-risk group, only 56.6% were located
there; however, this trend did not reach the level of statistical significance.
Taken together, the results from the present study suggested that CD168
expression patterns could potentially be used as a predictor of tumor
aggressiveness, and therefore they may be a prognostic factor in head-and-neck
SCC.
PMID- 28413677
TI - Management of afatinib-induced stomatitis.
AB - Severe stomatitis may lead to the need to interrupt or discontinue cancer therapy
and, thus, may affect control of the primary disease. Stomatitis may also
increase the risk of local and systemic infection and significantly affects the
quality of life and the cost of care. The present study was conducted to evaluate
the efficacy of two traditional herbal medicines in controlling treatment-induced
stomatitis in a small cohort of lung cancer patients treated with afatinib. All
patients who were treated with afatinib for epidermal growth factor receptor
(EGFR) mutated nonsmallcell lung cancer (NSCLC) between January, 2015 and March,
2016, were included in this study. During the study period, a total of 14 NSCLC
patients were treated with afatinib, an EGFR-tyrosine kinase inhibitor (TKI). Two
patients already had stomatitis at the time of initiation of afatinib therapy;
among the remaining 12 NSCLC patients, 2 (16.7%) developed stomatitis. All the
lesions in the 4 patients who developed stomatitis were completely alleviated
after 2 weeks of therapy with Aznol mouthwash, a chamomile extract with anti
inflammatory effects, and Hangeshashinto, a traditional herbal (Kampo) medicine.
Afatinib therapy was re-initiated, but none of the patients developed stomatitis
thereafter. To the best of our knowledge, this is the first report evaluating
oral care and management of stomatitis. This type of care and treatment may
reduce the incidence of complications associated with EGFR-TKI therapy.
PMID- 28413678
TI - The significance of multi-line chemotherapy for advanced gastric cancer: A
retrospective analysis.
AB - Palliative chemotherapy is known to benefit patients with advanced gastric cancer
by palliating symptoms and improving survival. The aim of the present study was
to evaluate the efficacy and toxicity of chemotherapy regimens that are commonly
used in patients with advanced or recurrent gastric cancer. Patients with
advanced or recurrent gastric cancer who were treated by at least two
chemotherapy regimens between May 2006 and July 2014 at Zhejiang Cancer Hospital
(Hangzhou, China) were retrospectively investigated. Survival was evaluated using
the Kaplan-Meier method. A total of 248 patients were reviewed, and 158 were
evaluated in the final analysis, with a median age of 57 years and a Karnofsky
performance status score of >=80. The median progression-free survival (PFS) time
was 168 days for first-line chemotherapy, 96 days for second-line chemotherapy,
and the median overall survival (OS) time was 356 days. Further analysis revealed
that patients with the disease controlled [complete response (CR) + partial
response (PR) + stable disease (SD)], no matter whether they received first-or
second-line chemotherapy, may have had an improved OS compared with patients with
disease progression (PD). Patients who were treated with >2 lines of chemotherapy
had an improved OS compared those who ceased treatment following failure of the
second-line chemotherapy. The cycle number of chemotherapy that patients received
was associated with OS. The site of the primary and metastatic tumors was also
associated with OS. Other factors, including gender, age, histological type,
whether a radical operation was received, and chemotherapy regimens, had no
evident association with survival. The toxicities were generally tolerated. Taken
together, the results from the present study have demonstrated that an increased
cycle number of effective chemotherapy may prolong the survival of patients with
advanced gastric cancer. Differences among the chemotherapy regimens had no clear
correlation with survival.
PMID- 28413679
TI - Anorectal functional outcome following laparoscopic low anterior resection for
rectal cancer.
AB - Low anterior resection (LAR) with total mesorectal excision has been considered a
standard treatment for patients with rectal cancer. However, the functional
outcome and life quality of laparoscopic LAR (LLAR) in Chinese patients remain
unclear. A cohort of 51 Chinese patients (22 men and 29 women) who had undergone
LLAR was included in this study. Anorectal manometry combined with the Wexner
scores questionnaire were applied to assess functional outcome preoperatively (1
week) and postoperatively (at 3, 6 and 9 months). The validated Chinese versions
of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ
CR38 questionnaires were also used to assess the patients' quality of life at the
indicated time points. The results demonstrated that the manometric parameters
exhibited a temporary decrease at 3 months postoperatively, but a gradual
increase at 6 and 9 months, while the Wexner scores exhibited an opposite trend.
Furthermore, patients with high anastomoses had significantly higher manometric
parameters, a lower frequency of incontinence and lower Wexner scores compared
with those with low anastomoses at 9 months (all P<0.05). For the entire cohort,
quality of life at 3 months postoperatively was worse compared with the
preoperative level, but returned to normal by 9 months. Patients with high
anastomoses exhibited significantly better role, emotional and social function,
had a better body image and sexual function, fewer problems with defecation and
lower frequency of diarrhea, as well as fewer chemotherapy-related side effects
at 6 months postoperatively when compared with the low anastomosis group (all
P<0.05). In conclusion, LLAR is generally acceptable for Chinese patients with
rectal cancer, particularly for those with middle or high rectal cancer, in terms
of functional outcome and quality of life.
PMID- 28413680
TI - Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment
of advanced gastric cancer: A phase-I clinical trial.
AB - Docetaxel, cisplatin and 5-fluorouracil (DCF regimen) are currently applied as an
effective combination treatment for various human malignancies; however, the
efficacy of this regimen is impaired by severe adverse events associated with it.
Therefore, better-tolerated regimens with comparable efficiency are required for
patients with gastric cancer. To explore such possibilities, a phase-I clinical
trial was performed to evaluate the safety and tolerability of a modified regimen
replacing cisplatin and 5-fluorouracil with oxaliplatin and capecitabine,
respectively (DOX program). The maximum-tolerated dose (MTD) and dose-limited
toxicity (DLT) of capecitabine in this regimen were determined and a dose for
subsequent phase-II clinical trials was identified. A total of 24 patients with
advanced gastric cancer were sequentially enrolled in the present capecitabine
dose-escalation trial. The patients were treated with docetaxel and oxaliplatin
at fixed doses [75 and 100 mg/m2, respectively, intravenously, on day 1 (d1)],
and with capecitabine at increasing doses (1,500, 2,000 and 2,500 mg/m2, per os,
d1-7). The MTD of capecitabine was 2,000 mg/m2 (d1-7), repeated every 21 days for
at least two cycles. The most frequent DLTs for this regimen were leukopenia
(15/24, 62.5%, all at grade-III/IV) and neutropenia (13/24, 54.2%, all at grade
III/IV), nausea (14/24, 58.3%, all at grade-III) and vomiting (13/24, 54.2%, all
at grade-III). The effective rate of the DOX regimen was 75.0% (18/24). Based on
the results, the combination of docetaxel (75 mg/m2, d1), oxaliplatin (100 mg/m2,
d1) and capecitabine (2,000 mg/m2, d1-7) is recommended for a future phase-II
trial. While these doses for the DOX regimen were generally well tolerated, the
efficacy of this modified regimen in patients with advanced gastric cancer
remains to be further evaluated in subsequent phase-II trials.
PMID- 28413681
TI - Phase 2 study of CHOP-R-14 followed by 90Y-ibritumomab tiuxetan in patients with
previously untreated diffuse large B-cell lymphoma.
AB - The aim of this open-label, single-center, phase 2 study was to assess the
efficacy and safety of dose-dense CHOP-R-14 followed by 90Y-ibritumomab
radioimmunotherapy (RIT) in patients with previously untreated diffuse large B
cell lymphoma (DLBCL). A total of 20 patients, the majority presenting with high
risk characteristics, were enrolled to receive dose-dense cyclophosphamide,
doxorubicin, vincristine, prednisone and rituximab every 14 days (CHOP-R-14),
followed by 90Y-ibritumomab tiuxetan consolidation. Sixteen patients completed
RIT consolidation (rituximab 250 mg/m2 on day 1 and day 7, 8, or 9, followed by a
single injection of 90Y-ibritumomab). Complete response (CR) rates of 75 and 95%
were observed after treatment with CHOP-R-14 and RIT, respectively; 4 of the 5
patients who achieved a partial response after CHOP-R-14 converted to CR
following treatment with RIT. With a median follow-up of 89.7 months, the
progression-free and overall survival rates for the cohort were 75 and 85%,
respectively. Hematological adverse events were common following CHOP-R-14 and
RIT, but they were manageable with treatment interruption. Therefore, this
regimen achieved promising survival outcomes in high-risk DLBCL on long term
follow-up, with manageable toxicity.
PMID- 28413682
TI - Multi-focal HIFU reduces cavitation in mild-hyperthermia.
AB - BACKGROUND: Mild-hyperthermia therapy (40-45 degrees C) with high-intensity
focused ultrasound (HIFU) is a technique being considered in a number of
different treatments such as thermally activated drug delivery, immune
stimulation, and as a chemotherapy adjuvant. Mechanical damage and loss of cell
viability associated with HIFU-induced acoustic cavitation may pose a risk during
these treatments or may hinder their success. Here we present a method that
achieves mild heating and reduces cavitation by using a multi-focused HIFU beam.
We quantify cavitation level and temperature rise in multi-focal sonications and
compare it to single-focus sonications at the transducer geometric focus.
METHODS: Continuous wave sonications were performed with the Sonalleve V2
transducer in gel phantoms and pork at 5, 10, 20, 40, 60, 80 acoustic watts for
30 s. Cavitation activity was measured with two ultrasound (US) imaging probes,
both by computing the raw channel variance and using passive acoustic mapping
(PAM). Temperature rise was measured with MR thermometry at 3 T. Cavitation and
heating were compared for single- and multi-focal sonication geometries. Multi
focal sonications used four points equally spaced on a ring of either 4 mm or 8
mm diameter. Single-focus sonications were not steered. RESULTS: Multi-focal
sonication generated distinct foci that were visible in MRI thermal maps in both
phantoms and pork, and visible in PAM images in phantoms only. Cavitation
activity (measured by channel variance) and mean PAM image value were highly
correlated (r > 0.9). In phantoms, cavitation exponentially decreased over the 30
second sonication, consistent with depletion of cavitation nuclei. In pork,
sporadic spikes signaling cavitation were observed with single focusing only. In
both materials, the widest beam reduced average and peak cavitation level by a
factor of two or more at each power tested when compared to a single focus. The
widest beam reduced peak temperature by at least 10 degrees C at powers above 5
W, and created heating that was more spatially diffuse than single focus,
resulting in more voxels in the mild heating (3-8 degrees C) range. CONCLUSIONS:
Multi-focal HIFU can be used to achieve mild temperature elevation and reduce
cavitation activity.
PMID- 28413683
TI - Obtaining accurate glucose measurements from wild animals under field conditions:
comparing a hand held glucometer with a standard laboratory technique in grey
seals.
AB - Glucose is an important metabolic fuel and circulating levels are tightly
regulated in most mammals, but can drop when body fuel reserves become critically
low. Glucose is mobilized rapidly from liver and muscle during stress in response
to increased circulating cortisol. Blood glucose levels can thus be of value in
conservation as an indicator of nutritional status and may be a useful, rapid
assessment marker for acute or chronic stress. However, seals show unusual
glucose regulation: circulating levels are high and insulin sensitivity is
limited. Accurate blood glucose measurement is therefore vital to enable
meaningful health and physiological assessments in captive, wild or rehabilitated
seals and to explore its utility as a marker of conservation relevance in these
animals. Point-of-care devices are simple, portable, relatively cheap and use
less blood compared with traditional sampling approaches, making them useful in
conservation-related monitoring. We investigated the accuracy of a hand-held
glucometer for 'instant' field measurement of blood glucose, compared with blood
drawing followed by laboratory testing, in wild grey seals (Halichoerus grypus),
a species used as an indicator for Good Environmental Status in European waters.
The glucometer showed high precision, but low accuracy, relative to laboratory
measurements, and was least accurate at extreme values. It did not provide a
reliable alternative to plasma analysis. Poor correlation between methods may be
due to suboptimal field conditions, greater and more variable haematocrit, faster
erythrocyte settling rate and/or lipaemia in seals. Glucometers must therefore be
rigorously tested before use in new species and demographic groups. Sampling,
processing and glucose determination methods have major implications for
conclusions regarding glucose regulation, and health assessment in seals
generally, which is important in species of conservation concern and in
development of circulating glucose as a marker of stress or nutritional state for
use in management and monitoring.
PMID- 28413684
TI - Physiological effects of environmentally relevant, multi-day thermal stress on
wild juvenile Atlantic salmon (Salmo salar).
AB - The frequency of extreme thermal events in temperate freshwater systems is
expected to increase alongside global surface temperature. The Miramichi River,
located in eastern Canada, is a prominent Atlantic salmon (Salmo salar) river
where water temperatures can exceed the proposed upper thermal limit for the
species (~27 degrees C). Current legislation closes the river to recreational
angling when water temperatures exceed 20 degrees C for two consecutive nights.
We aimed to examine how natural thermal variation, representative of extreme high
thermal events, affected the thermal tolerance and physiology of wild, juvenile
Atlantic salmon. We acclimated fish to four thermal cycles, characteristic of
real-world thermal conditions while varying daily thermal minima (16 degrees C,
18 degrees C, 20 degrees C or 22 degrees C) and diel thermal fluctuation (e.g.
Delta5 degrees C-Delta9 degrees C). In each cycling condition, we assessed the
role that thermal minima played on the acute thermal tolerance (critical thermal
maximum, (CTMax)), physiological (e.g. heat shock protein 70 (HSP70), ubiquitin)
and energetic (e.g. hepatic glycogen, blood glucose and lactate) status of
juvenile Atlantic salmon throughout repeated thermal cycles. Exposure to 16-21
degrees C significantly increased CTMax (+0.9 degrees C) compared to a stable
acclimation temperature (16 degrees C), as did exposure to diel thermal
fluctuations of 18-27 degrees C, 20-27 degrees C and 22-27 degrees C, yet
repeated exposure provided no further increases in acute thermal tolerance. In
comparison to the reference condition (16-21 degrees C), consecutive days of high
temperature cycling with different thermal minima resulted in significant
increases in HSP70 and ubiquitin, a significant decrease in liver glycogen, and
no significant cumulative effect on either blood glucose or lactate. However,
comparison between thermally taxed treatments suggested the diel thermal minima
had little influence on the physiological or energetic response of juvenile
salmon, despite the variable thermal cycling condition. Our results suggest that
relatively cooler night temperatures in the summer months may play a limited role
in mitigating physiological stress throughout warm diel cycle events.
PMID- 28413685
TI - Empyema associated with Campylobacter curvus infection.
AB - We report the first case of thoracic empyema associated with Campylobacter curvus
infection. A 65-year-old woman with a history of bronchiectasis presented with
acute cough and phlegm. The patient reported dyspnoea and left chest pain
accompanied by left pleural effusion, despite treatment with sitafloxacin. Curved
Gram-negative rods, eventually identified as C. curvus using 16S ribosomal RNA-
and atpA-specific polymerase chain reaction (PCR) and sequencing, were cultured
in anaerobic condition of pleural effusion together with Peptostreptococci. The
patient recovered after thoracic drainage and treatment with ampicillin/sulbactam
and clindamycin. C. curvus, an anaerobe present in human oral cavity, can be
associated with extra-oral infections such as empyema.
PMID- 28413686
TI - Cytokine profiles of amyopathic dermatomyositis with interstitial lung diseases
treated with mycophenolate.
AB - A 59-year-old Japanese man diagnosed with interstitial lung disease associated
with amyopathic dermatomyositis with anti-melanoma differentiation-associated
gene 5 (MDA-5) antibodies was treated with intravenous methyl prednisolone (PSL)
1000 mg, oral PSL 1 mg/kg, and oral cyclosporin 200 mg daily. His respiratory
condition worsened after treatment with two times of intravenous cyclophosphamide
and another steroid pulse therapy as well as PSL and cyclosporin. Addition of
mycophenolate mofetil (MMF), 1.5 g daily improved PaO2/FiO2 (PF) ratio of the
patient from 294 to 360 at 4 weeks and 416 at 15 weeks after addition of MMF. We
measured cytokine concentration in preserved serum taken at 11 and 7 weeks before
addition of MMF and at 4, 11, and 15 weeks after MMF administration. Of the 28
cytokines evaluated, the concentrations of fibroblast growth factors-2 (FGF-2),
chemokine (C-X3-C motif) ligand 1 (CX3CL1), interleukin (IL)-1ra, IL-17A,
inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1)
decreased after addition of MMF. These results suggest that MMF may be beneficial
to patients with interstitial lung disease by modification of the cytokine/growth
factor protein expression.
PMID- 28413687
TI - What we have changed our minds about: Part 1. Borderline personality disorder as
a limitation of resilience.
AB - This paper sets out a recent transition in our thinking in relation to
psychopathology associated with personality disorder, in an approach that
integrates our thinking about attachment, mentalizing (understanding ourselves
and others in terms of intentional mental states) and epistemic trust (openness
to the reception of social communication that is personally relevant and of
generalizable significance) with recent findings on the structure of both adult
and child psychopathology and resilience. In this paper - the first of two parts
we review evidence suggesting that a general psychopathology or p factor
underlies vulnerability for psychopathology. We link this p factor to a lack of
resilience using Kalisch and colleagues' positive appraisal style theory of
resilience (PASTOR). We argue that vulnerability for (severe) psychopathology
results from impairments in three central mechanisms underlying resilience -
positive situation classification, retrospective reappraisal of threat, and
inhibition of retraumatizing triggers - which in turn result from a lack of
flexibility in terms of social communicative processes. We suggest that, from
this perspective, personality disorders, and borderline personality disorder
(BPD) in particular, can be considered to be the prototype of disorders
characterized by a lack of resilience. Part 2 proposes an evolutionary
developmental psychopathology account linking this inflexibility in social
communication to problems with the development of epistemic trust - that is, an
evolutionary pre-wired social communication system that normally facilitates
resilience through salutogenesis, that is, the capacity to learn and derive
benefit from the (social) environment.
PMID- 28413688
TI - Presentation and care of a family with Huntington disease in a resource-limited
community.
AB - BACKGROUND: In high-income countries patients with Huntington disease (HD)
typically present to healthcare providers after developing involuntary movements,
or for pre-symptomatic genetic testing if at familial risk. A positive family
history is a major guide when considering the decision to perform genetic testing
for HD, both in affected and unaffected patients. Management of HD is focused
upon control of symptoms, whether motor, cognitive, or psychiatric. There is no
clear evidence to date of any disease-modifying agents. Referral of families and
caregivers for psychological and social support, whether to HD-focused centers,
or through virtual communities, is viewed as an important consequence of
diagnosis. The experience of healthcare for such progressive neurodegenerative
diseases in low- and middle-income nations is in stark contrast with the standard
of care in high-income countries. METHODS: An extended family with many members
affected with an autosomal dominantly inherited movement disorder came to medical
attention when one family member presented following a fall. Apart from one
family member who was taking a benzodiazepine for involuntary movements, no other
affected family members had sought medical attention. Members of this family live
on several resource-limited Caribbean islands. Care of the chronically ill is
often the responsibility of the family, and access to specialty care is difficult
to obtain, or is unavailable. Computed tomography scan of one patient's brain
revealed severe caudate atrophy and moderate generalized cortical atrophy.
Genetic diagnosis of HD was obtained. RESULTS: Through family recollection and by
direct observation we identified four generations of individuals affected with
HD. Outreach programs and collaborations helped to provide medical imaging and
genetic diagnosis. Additionally these efforts helped with patient and family
support, education, and genetic counseling to many members of this family.
CONCLUSIONS: Affected members of this family have limited healthcare access, and
rely heavily on family support for care. Genetic and clinical diagnosis of these
patients was impeded by lack of resources and lack of access to specialty care.
Importantly, obtaining a definitive diagnosis has had a positive impact for this
family by facilitating genetic counseling, education, community outreach, and
dispelling myths regarding this hereditary disease and its progression.
PMID- 28413689
TI - L1000CDS2: LINCS L1000 characteristic direction signatures search engine.
AB - The library of integrated network-based cellular signatures (LINCS) L1000 data
set currently comprises of over a million gene expression profiles of chemically
perturbed human cell lines. Through unique several intrinsic and extrinsic
benchmarking schemes, we demonstrate that processing the L1000 data with the
characteristic direction (CD) method significantly improves signal to noise
compared with the MODZ method currently used to compute L1000 signatures. The CD
processed L1000 signatures are served through a state-of-the-art web-based search
engine application called L1000CDS2. The L1000CDS2 search engine provides
prioritization of thousands of small-molecule signatures, and their pairwise
combinations, predicted to either mimic or reverse an input gene expression
signature using two methods. The L1000CDS2 search engine also predicts drug
targets for all the small molecules profiled by the L1000 assay that we
processed. Targets are predicted by computing the cosine similarity between the
L1000 small-molecule signatures and a large collection of signatures extracted
from the gene expression omnibus (GEO) for single-gene perturbations in mammalian
cells. We applied L1000CDS2 to prioritize small molecules that are predicted to
reverse expression in 670 disease signatures also extracted from GEO, and
prioritized small molecules that can mimic expression of 22 endogenous ligand
signatures profiled by the L1000 assay. As a case study, to further demonstrate
the utility of L1000CDS2, we collected expression signatures from human cells
infected with Ebola virus at 30, 60 and 120 min. Querying these signatures with
L1000CDS2 we identified kenpaullone, a GSK3B/CDK2 inhibitor that we show, in
subsequent experiments, has a dose-dependent efficacy in inhibiting Ebola
infection in vitro without causing cellular toxicity in human cell lines. In
summary, the L1000CDS2 tool can be applied in many biological and biomedical
settings, while improving the extraction of knowledge from the LINCS L1000
resource.
PMID- 28413690
TI - A dynamic model for GPS based attitude determination and testing using a serial
robotic manipulator.
AB - A computational algorithm is developed for estimating accurately the attitude of
a robotic arm which moves along a predetermined path. This algorithm requires
preliminary input data obtained in the static mode to yield phase observables for
the precise, 3-axis attitude determination of a swinging manipulator in the
dynamic mode. Measurements are recorded simultaneously by three GPS L1 receivers
and then processed in several steps to accomplish this task. First, artkconv
batch executable converts GPS receiver readings into RINEX format to generate GPS
observables and ephemeris for multiple satellites. Then baseline vectors
determination is carried out by baseline constrained Least-Squares Ambiguity
Decorrelation (LAMBDA) method that uses double difference carrier phase estimates
as input to calculate integer solution for each baseline. Finally, attitude
determination is made by employing alternatively Least-squares attitude
determination (LSAD) in the static mode and extended Kalman filter in the dynamic
mode. The algorithm presented in this paper is applied to recorded data on
Mitsubishi RV-M1 robotic arm in order to produce attitude estimates. These
results are confirmed by another set of Euler angles independently evaluated from
robotic arm postures obtained along the predefined trajectory.
PMID- 28413691
TI - Proton Transfer in the Catalytic Cycle of [NiFe] Hydrogenases: Insight from
Vibrational Spectroscopy.
AB - Catalysis of H2 production and oxidation reactions is critical in renewable
energy systems based around H2 as a clean fuel, but the present reliance on
platinum-based catalysts is not sustainable. In nature, H2 is oxidized at minimal
overpotential and high turnover frequencies at [NiFe] catalytic sites in
hydrogenase enzymes. Although an outline mechanism has been established for the
[NiFe] hydrogenases involving heterolytic cleavage of H2 followed by a first and
then second transfer of a proton and electron away from the active site, details
remain vague concerning how the proton transfers are facilitated by the protein
environment close to the active site. Furthermore, although [NiFe] hydrogenases
from different organisms or cellular environments share a common active site,
they exhibit a broad range of catalytic characteristics indicating the importance
of subtle changes in the surrounding protein in controlling their behavior. Here
we review recent time-resolved infrared (IR) spectroscopic studies and IR
spectroelectrochemical studies carried out in situ during electrocatalytic
turnover. Additionally, we re-evaluate the significant body of IR spectroscopic
data on hydrogenase active site states determined through more conventional
solution studies, in order to highlight mechanistic steps that seem to apply
generally across the [NiFe] hydrogenases, as well as steps which so far seem
limited to specific groups of these enzymes. This analysis is intended to help
focus attention on the key open questions where further work is needed to assess
important aspects of proton and electron transfer in the mechanism of [NiFe]
hydrogenases.
PMID- 28413693
TI - Stable Fe/ZSM-5 Nanosheet Zeolite Catalysts for the Oxidation of Benzene to
Phenol.
AB - Fe/ZSM-5 nanosheet zeolites of varying thickness were synthesized with di- and
tetraquaternary ammonium structure directing agents and extensively characterized
for their textural, structural, and catalytic properties. Introduction of Fe3+
ions in the framework of nanosheet zeolites was slightly less effective than in
bulk ZSM-5 zeolite. Steaming was necessary to activate all catalysts for N2O
decomposition and benzene oxidation. The higher the Fe content, the higher the
degree of Fe aggregation was after catalyst activation. The degree of Fe
aggregation was lower when the crystal domain size of the zeolite or the Fe
content was decreased. These two parameters had a substantial influence on the
catalytic performance. Decreasing the number of Fe sites along the b-direction
strongly suppressed secondary reactions of phenol and, accordingly, catalyst
deactivation. This together with the absence of diffusional limitations in
nanosheet zeolites explains the much higher phenol productivity obtainable with
nanostructured Fe/ZSM-5. Steamed Fe/ZSM-5 zeolite nanosheet synthesized using C22
6-3.Br2 (domain size in b-direction ~3 nm) and containing 0.24 wt % Fe exhibited
the highest catalytic performance. During the first 24 h on stream, this catalyst
produced 185 mmolphenol g-1. Calcination to remove the coke deposits completely
restored the initial activity.
PMID- 28413692
TI - Photoredox-Mediated Routes to Radicals: The Value of Catalytic Radical Generation
in Synthetic Methods Development.
AB - Photoredox catalysis has experienced a revitalized interest from the synthesis
community during the past decade. For example, photoredox/Ni dual catalysis
protocols have been developed to overcome several inherent limitations of
palladium-catalyzed cross-couplings by invoking a single-electron transmetalation
pathway. This Perspective highlights advances made by our laboratory since the
inception of the photoredox/Ni cross-coupling of benzyltrifluoroborates with aryl
bromides. In addition to broadening the scope of trifluoroborate coupling
partners, research using readily oxidized hypervalent silicates as radical
precursors that demonstrate functional group compatibility is highlighted. The
pursuit of electrophilic coupling partners beyond (hetero)aryl bromides has also
led to the incorporation of several new classes of C(sp2)-hybridized substrates
into light-mediated cross-coupling. Advances to expand the radical toolbox by
utilizing feedstock chemicals (e.g., aldehydes) to access radicals that were
previously inaccessible from trifluoroborates and silicates are also emphasized.
Additionally, several organic photocatalysts have been investigated as
replacements for their expensive iridium- and ruthenium-based counterparts.
Lastly, the net C-H functionalization of the radical partner in an effort to
improve atom economy is presented. An underlying theme in all of these studies is
the value of generating radicals in a catalytic manner, rather than
stoichiometrically.
PMID- 28413694
TI - First Neonatal Demise with Travel-Associated Zika Virus Infection in the United
States of America.
AB - Zika virus is increasingly recognized as a fetal pathogen worldwide. We describe
the first case of neonatal demise with travel-associated Zika virus infection in
the United States of America, including a novel prenatal ultrasound finding. A
young Latina presented to our health care system in Southeast Texas for prenatal
care at 23 weeks of gestation. Fetal Dandy-Walker malformation, asymmetric
cerebral ventriculomegaly, single umbilical artery, hypoechoic fetal knee, dorsal
foot edema, and mild polyhydramnios were noted upon initial screening prenatal
sonography at 26 weeks. A growth-restricted, microcephalic, and arthrogrypotic
infant was delivered alive at 36 weeks but died within an hour despite
resuscitation. The neonatal karyotype was normal. Flavivirus IgM antibodies were
identified in the serum of the puerpera, once she disclosed that she had traveled
from El Salvador to Texas in the early second trimester. Zika virus was
identified in the umbilical cord and neonatal brain. Fetal arthritis may precede
congenital arthrogryposis in cases of Zika virus infection and may be detectable
by prenatal sonography. Physician and health care system vigilance is required to
optimally address the significant and enduring Zika virus global health threat.
PMID- 28413695
TI - One-step Quantitative RT-PCR Assays for Detecting, Genotyping and Differentiating
Wild-Type Group a Rotaviruses and Vaccine (Rotarix(r) and RotaTeq(r)) Strains in
Stool Samples.
PMID- 28413696
TI - Prevalence of potential sports-associated risk factors in Swiss amyotrophic
lateral sclerosis patients.
AB - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) has been reported to occur with
increased incidence amongst physically active people. The role of extrinsic risk
factors as physical activity, head trauma and drug/pesticide-exposure in the
pathophysiology of ALS and especially in the context of practising sports remains
controversial. MATERIALS AND METHODS: We retrospectively studied exposure to
extrinsic factors in 92 ALS patients in the presymptomatic stage. Metabolic
equivalents (METs) were calculated and the association of physical activity, drug
intake, head trauma and participation in specific sports (football [soccer], ice
hockey) with age at symptom-onset was evaluated. RESULTS: Ninety-five percent of
patients considered themselves physically active before symptom-onset. Total MET
values varied broadly and there was no correlation between vigorous physical
activity and age at symptom-onset. Mild traumatic brain injury (prevalence =
16.7%) was the most frequent diagnosis after head/neck injury. A history of >=1
head/neck injuries was associated with a younger age at symptom-onset (61.8 +/-
11.0 vs. 54.1 +/- 13.0, p = .013). In former football and ice hockey players the
rate of vigorous physical activities was increased (p < .05), whereas total MET
values, frequency of head injuries and analgesic intake were not different
compared to other ALS patients. CONCLUSIONS: History of head injuries was the
only extrinsic risk factor associated with accelerated neurodegeneration in ALS.
There was no evidence for extrinsic factors predisposing former football and ice
hockey players to ALS. Our data therefore support the hypothesis that not
increased physical activity per se, but other unknown environmental factors
and/or genetic profile or lifestyle-promoting physical fitness increases ALS
susceptibility.
PMID- 28413697
TI - Acute ethanol exposure during late mouse neurodevelopment results in long-term
deficits in memory retrieval, but not in social responsiveness.
AB - OBJECTIVE: Prenatal alcohol exposure can result in neurological changes in
affected individuals and may result in the emergence of a broad spectrum of
neurobehavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The
effects of ethanol exposure during development are both time and dose dependent.
Although many animal models of FASD use more chronic ethanol exposure, acute
developmental alcohol exposure may also cause long-lasting neuronal changes. Our
research employed behavioral measures to assess the effects of a single early
postnatal ethanol intoxication event in mice. MATERIALS AND METHODS: Mice were
dosed at postnatal day 6 (a 2.5 g/kg dose of ethanol or a saline control
administered twice, 2 hr apart) as a model of third trimester binge drinking in
humans. This exposure was followed by behavioral assessment in male mice at 1
month (1M) and at 4 months of age (4M), using the Barnes maze (for
learning/memory retrieval), exploratory behavior, and a social responsiveness
task. RESULTS: Ethanol-exposed mice appeared to be less motivated to complete the
Barnes maze at 1M, but were able to successfully learn the maze. However,
deficits in long-term spatial memory retrieval were observed in ethanol-exposed
mice when the Barnes maze recall was measured at 4M. No significant differences
were found in open field behavior or social responsiveness at 1M or 4M of age.
CONCLUSIONS: Acute ethanol exposure at P6 in mice leads to mild but long-lasting
deficits in long-term spatial memory. Results suggest that even brief acute
exposure to high ethanol levels during the third trimester equivalent of human
pregnancy may have a permanent negative impact on the neurological functioning of
the offspring.
PMID- 28413698
TI - Simultaneous bilateral cochlear implants: Developmental advances do not yet
achieve normal cortical processing.
AB - BACKGROUND: Simultaneous bilateral cochlear implantation promotes symmetric
development of bilateral auditory pathways but binaural hearing remains abnormal.
To evaluate whether bilateral cortical processing remains impaired in such
children, cortical activity to unilateral and bilateral stimuli was assessed in a
unique cohort of 16 children who received bilateral cochlear implants (CIs)
simultaneously at 1.97 +/- 0.86 years of age and had ~4 years of CI experience,
providing the first opportunity to assess electrically driven cortical
development in the absence of reorganized asymmetries from sequential
implantation. METHODS: Cortical activity to unilateral and bilateral stimuli was
measured using multichannel electro-encephalography. Cortical processing in
children with bilateral CIs was compared with click-elicited activity in 13
normal hearing children matched for time-in-sound. Source activity was localized
using the Time Restricted, Artefact and Coherence source Suppression (TRACS)
beamformer method. RESULTS: Consistent with dominant crossed auditory pathways,
normal P1 activity (~100 ms) was weaker to ipsilateral stimuli relative to
contralateral and bilateral stimuli and both auditory cortices preferentially
responded to the contralateral ear. Right hemisphere dominance was evident
overall. Children with bilateral CIs maintained the expected right dominance but
differences from normal included: (i) minimal changes between ipsilateral,
contralateral and bilateral stimuli, (ii) weaker than normal contralateral
stimulus preference, (iii) symmetric activity to bilateral stimuli, and (iv)
increased occipital lobe recruitment during bilateral relative to unilateral
stimulation. Between-group contrasts demonstrated lower than normal activity in
the inferior parieto-occipital lobe (suggesting deficits in sensory integration)
and greater than normal left frontal lobe activity (suggesting increased
attention), even during passive listening. CONCLUSIONS: Together, findings
suggest that early simultaneous bilateral cochlear implantation promotes normal
like auditory symmetry but that abnormalities in cortical processing consequent
to deafness and/or electrical stimulation through two independent speech
processors persist.
PMID- 28413699
TI - White matter connections of the inferior parietal lobule: A study of surgical
anatomy.
AB - INTRODUCTION: Interest in the function of the inferior parietal lobule (IPL) has
resulted in increased understanding of its involvement in visuospatial and
cognitive functioning, and its role in semantic networks. A basic understanding
of the nuanced white-matter anatomy in this region may be useful in improving
outcomes when operating in this region of the brain. We sought to derive the
surgical relationship between the IPL and underlying major white-matter bundles
by characterizing macroscopic connectivity. METHODS: Data of 10 healthy adult
controls from the Human Connectome Project were used for tractography analysis.
All IPL connections were mapped in both hemispheres, and distances were recorded
between cortical landmarks and major tracts. Ten postmortem dissections were then
performed using a modified Klingler technique to serve as ground truth. RESULTS:
We identified three major types of connections of the IPL. (1) Short association
fibers connect the supramarginal and angular gyri, and connect both of these gyri
to the superior parietal lobule. (2) Fiber bundles from the IPL connect to the
frontal lobe by joining the superior longitudinal fasciculus near the termination
of the Sylvian fissure. (3) Fiber bundles from the IPL connect to the temporal
lobe by joining the middle longitudinal fasciculus just inferior to the margin of
the superior temporal sulcus. CONCLUSIONS: We present a summary of the relevant
anatomy of the IPL as part of a larger effort to understand the anatomic
connections of related networks. This study highlights the principle white-matter
pathways and highlights key underlying connections.
PMID- 28413700
TI - Endovascular stroke treatment in a small-volume stroke center.
AB - INTRODUCTION: Our purpose was to evaluate the safety and efficacy of endovascular
treatment (EVT) of stroke caused by large vessel occlusions (LVO) performed by
general interventional radiologists in cooperation with stroke neurologists and
neuroradiologists at a center with a limited annual number of procedures. We
aimed to compare our results with those previously reported from larger stroke
centers. PATIENTS AND METHODS: A total of 108 patients with acute stroke due to
LVO treated with EVT were included. Outcome was measured using the modified
Rankin scale (mRS) at 90 days. Efficacy was classified according to the modified
thrombolysis in cerebral infarction (mTICI) scoring system. Safety was evaluated
according to the incidence of procedural complications and symptomatic
intracranial hemorrhage (sICH). RESULTS: Mean age of the patients was 67.5 years.
The median National Institutes of Health Stroke Scale (NIHSS) on hospital
admission was 17. Successful revascularization was achieved in 76%. 39.4%
experienced a good clinical outcome (mRS<3). Intraprocedural complications were
seen in 7.4%. 7.4% suffered a sICH. 21.3% died within 3 months after EVT.
DISCUSSION: The use of general interventional radiologists in EVT of LVO may be a
possible approach for improving EVT coverage where availability of specialized
neurointerventionalists is challenging. EVT for LVO stroke performed by general
interventional radiologists in close cooperation with diagnostic
neuroradiologists and stroke neurologists can be safe and efficacious despite the
low number of annual procedures.
PMID- 28413701
TI - Elevated C-X-C motif ligand 13 and B-cell-activating factor levels in
neuromyelitis optica during remission.
AB - BACKGROUND: Discovery of specific antibodies against astrocytic water channel
aquaporin-4 (AQP4), which is produced by plasma cells, in the serum of
neuromyelitis optica (NMO) confirmed the pathogenic role of B cells in NMO. C-X-C
motif ligand 13 (CXCL13) and B-cell-activating factor (BAFF) are two crucial
factors for antibody production. Relevant studies have focused on the acute phase
of NMO. However, CXCL13 and BAFF levels during remission, remain to be
elucidated. OBJECTIVE: To evaluate serum levels of CXCL13 and BAFF in NMO and
multiple sclerosis (MS) patients during remission and explore their correlation
with immunosuppressive agents and clinical features in NMO. METHODS: Serum CXCL13
and BAFF were measured by enzyme-linked immunosorbent assay (ELISA) in NMO
patients, MS patients, and controls. RESULTS: Serum CXCL13 levels of NMO patients
(n = 24) were significantly higher than those of controls (n = 22) (p = .001),
but CXCL13 levels of MS patients (n = 20) and controls (n = 22) did not differ
significantly (p = .279). Although the three groups showed no differences in
serum BAFF levels, serum BAFF levels of NMO patients without immunosuppressive
treatment (n = 8) were significantly elevated compared with those of NMO patients
with immunosuppressive therapy (n = 16) (p = .003) and controls (n = 22) (p =
.024). In NMO patients, CXCL13 levels were correlated with onset age (p = .026)
and duration to the last relapse (p = .003). CONCLUSION: During remission, serum
CXCL13 and BAFF levels have not decreased to normal in NMO patients, and B-cell
related autoimmune response persists. Immunosuppressive therapy decreased serum
BAFF levels, but did not affect CXCL13 expression.
PMID- 28413702
TI - Targeted sequencing identifies genetic polymorphisms of flavin-containing
monooxygenase genes contributing to susceptibility of nicotine dependence in
European American and African American.
AB - BACKGROUND: Smoking is a leading cause of preventable death. Early studies based
on samples of twins have linked the lifetime smoking practices to genetic
predisposition. The flavin-containing monooxygenase (FMO) protein family consists
of a group of enzymes that metabolize drugs and xenobiotics. Both FMO1 and FMO3
were potentially susceptible genes for nicotine metabolism process. METHODS: In
this study, we investigated the potential of FMO genes to confer risk of nicotine
dependence via deep targeted sequencing in 2,820 study subjects comprising 1,583
nicotine dependents and 1,237 controls from European American and African
American. Specifically, we focused on the two genomic segments including
FMO1,FMO3, and pseudo gene FMO6P, and aimed to investigate the potential
association between FMO genes and nicotine dependence. Both common and low
frequency/rare variants were analyzed using different algorithms. The potential
functional significance of SNPs with association signal was investigated with
relevant bioinformatics tools. RESULTS: We identified different clusters of
significant common variants in European (with most significant SNP rs6674596, p =
.0004, OR = 0.67, MAF_EA = 0.14, FMO1) and African Americans (with the most
significant SNP rs6608453, p = .001, OR = 0.64, MAF_AA = 0.1, FMO6P). No
significant signals were identified through haplotype-based analyses. Gene
network investigation indicated that both FMO1 and FMO3 have a strong relation
with a variety of genes belonging to CYP gene families (with combined score
greater than 0.9). Most of the significant variants identified were SNPs located
within intron regions or with unknown functional significance, indicating a need
for future work to understand the underlying functional significance of these
signals. CONCLUSIONS: Our findings indicated significant association between FMO
genes and nicotine dependence. Replications of our findings in other ethnic
groups were needed in the future. Most of the significant variants identified
were SNPs located within intronic regions or with unknown functional
significance, indicating a need for future work to understand the underlying
functional significance of these signals.
PMID- 28413703
TI - Lifelong neurogenesis in the cerebral ganglion of the Chinese mud snail,
Cipangopaludina chinensis.
AB - INTRODUCTION: A small group of Gastropods possessing giant neurons have long been
used to study a wide variety of fundamental neurophysiological phenomena.
However, the majority of gastropods do not have large neurons but instead have
large numbers of small neurons and remain largely unstudied. We explored neuron
size and rate of increase in neuron numbers in the Chinese mud snail,
Cipangopaludina chinensis. METHODS: Using histological sections and whole mounts
of the cerebral ganglia, we collected cross-sectional data on neuron number and
size across the lifespan of this animal. Neurogenesis was verified using Click-it
EdU staining. RESULTS: We found that total neuron number in the cerebral ganglia
increases throughout the lifespan of this species at a constant rate. New neurons
arise primarily near the nerve roots. Females live longer (up to 7 years) than
males (up to 5 years) and thus achieve larger numbers of neurons in the cerebral
ganglion. Neuron size is consistently small (<10 MUm) in the cerebral ganglia at
all ages, however, cells in the posterior section of the cerebral ganglia are
modestly but significantly larger than cells at the anterior. CONCLUSIONS: These
features suggest that C. chinensis and similar species of Caenogastropoda are
good candidates for studying gastropod neurogenesis, senescence, and sex
differences in the nervous system.
PMID- 28413704
TI - Diversity in mental fatigue and social profile of patients with myasthenia gravis
in two different Northern European countries.
AB - : Self-estimated health can be used for comparison of different diseases between
countries. It is important to elaborate on whether disparities in self-estimated
health are due to disease-specific parameters or socioeconomic differences. In
this study, we aimed at evaluating clinical and social similarities and
differences in myasthenia gravis (MG) patients between comparable regions in two
Baltic Sea countries, Estonia and Sweden. METHODS: This cross-sectional study
included southern counties in Sweden and Estonia of comparable size. All patients
with a confirmed MG diagnosis were asked to answer two questionnaires including
demographic and disease-specific data, lifestyle issues, and mental fatigue
(Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through
the Quantitative Myasthenia Gravis Score (QMG). RESULTS: Thirty-six of 92
identified patients in Estonia and 40 of 70 identified MG patients in Sweden
chose to participate in the study. The demographic characteristics and symptoms
reported by the patients were similar. QMG score did not differ; however, the
Estonian patients scored their current subjective disease severity significantly
higher (5.6 +/- 2.8) compared to the Swedish patients (3.4 +/- 2.3, p = .0005).
Estonian patients also had significantly higher FSS scores (5.0 +/- 1.7) than
Swedish patients (3.5 +/- 1.6; p = .001). Swedish patients were more active and
performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden,
p = .004). CONCLUSIONS: Although, the patients had comparable clinical fatigue,
Estonian patients evaluated their health state as being more severe and reported
more mental fatigue than Swedish patients. These data indicate large regional
differences in disease perception of MG, which is important to consider in
international studies.
PMID- 28413705
TI - Acute stroke alert activation, emergency service use, and reperfusion therapy in
Sweden.
AB - OBJECTIVES: Ambulance services and stroke alerts reduce the time from stroke
onset to acute stroke diagnosis. We describe the use of stroke alerts and
ambulance services in different hospitals and patient groups and their
relationship with reperfusion therapy. METHODS: This nationwide study included
49,907 patients admitted with acute stroke who were registered in The Swedish
Stroke Register (Riksstroke) in 2011-2012. RESULTS: The proportions of patients
admitted as stroke alerts out of all acute stroke admissions varied from 12.2% to
45.7% in university hospitals (n = 9), 0.5% to 38.7% in specialized nonuniversity
hospitals (n = 22), and 4.2% to 40.3% in community hospitals (n = 41). Younger
age, atrial fibrillation (AF), living in an institution, reduced consciousness
upon admission, and hemorrhagic stroke were factors associated with a higher
probability of stroke alerts. Living alone, primary school education, non
European origin, previous stroke, diabetes, smoking, and dependency in activities
of daily living (ADL) were associated with a lower probability of stroke alert.
The proportion of patients arriving at the hospital by ambulance varied from
60.3% to 94.5%. Older age, living alone, primary school education, being born in
a European country, previous stroke, AF, dependency in ADL, living in an
institution, reduced consciousness upon admission, and hemorrhagic stroke were
associated with ambulance services. Hospital stroke alert frequencies correlated
strongly with reperfusion rates (r = .75). CONCLUSION: Acute stroke alerts have a
significant potential to improve stroke reperfusion rates. Prehospital stroke
management varies conspicuously between hospitals and patient groups, and the
elderly and patients living alone have a markedly reduced likelihood of stroke
alerts.
PMID- 28413706
TI - Basic taste processing recruits bilateral anteroventral and middle dorsal
insulae: An activation likelihood estimation meta-analysis of fMRI studies.
AB - BACKGROUND AND PURPOSE: Numerous task-based functional magnetic resonance imaging
(fMRI) studies have reported the locations of basic taste representations in the
human brain, but they usually employed a limited number of subjects (<20) with
different methodologies and stimuli. Moreover, the reported brain regions were
sometimes inconsistent. Thus, we aimed at performing a meta-analysis of the
published data to identify locations consistently activated across studies, and
performed a connectivity analysis to reveal how these taste processing regions
connect with other brain regions. MATERIALS AND METHODS: A meta-analysis was
performed based on 34 experiments, with 238 total participants in 16 studies, to
establish the activation likelihood estimation (ALE) of taste-mediated regional
activation. Meta-analytic connectivity modeling (MACM) and data stored in
BrainMap database were employed to reveal the functional connectivity of the
regions identified by ALE with other brain regions, across all types of
experiments that caused activation among healthy subjects. RESULTS: ALE
identified nine activated clusters in bilateral anteroventral and middle dorsal
insulae, bilateral thalamus and caudate, bilateral pre-/postcentral gyrus, and
right hippocampus. The concurrence between studies was moderate, with at best 38%
of experiments contributed to the significant clusters activated by taste
stimulation. Sweet taste was the predominant contributing taste. MACM revealed
that at least 50% of the nine clusters coactivated with the middle cingulate
cortex, medial frontal gyrus, inferior parietal lobule, and putamen. CONCLUSION:
Results suggested that fMRI studies have reported reproducible patterns of
activations across studies. The basic taste stimulations resulted in activations
in a mostly bilateral network. Moreover, they were connected with cognitive and
emotional relevant brain regions.
PMID- 28413707
TI - Disrupting dorsolateral prefrontal cortex by rTMS reduces the P300 based marker
of deception.
AB - OBJECTIVE: Quite many studies have revealed certain brain-process signatures
indicative of subject's deceptive behavior. These signatures are neural
correlates of deception. However, much less is known about whether these
signatures can be modified by noninvasive brain stimulation techniques
representing methods of causal intervention of brain processes and the
corresponding behavior. Our purpose was to explore whether such methods have an
effect on these signatures. METHODS: It is well known that
electroencephalographic event-related potential component, P300, is sensitive to
perception of critical items in a concealed information test, one of the central
methods in deception studies. We examined whether the relative level of
expression of P300 as a neural marker of deception can be manipulated by means of
noninvasive neuromodulation. We used EEG/ERP recording combined with (i)
neuronavigated repetitive transcranial magnetic stimulation (rTMS) and (ii)
concealed information detection test. An opportunistically recruited volunteer
group of normal adults formed our experimental group. RESULTS: We show that
offline rTMS to dorsolateral prefrontal cortex attenuated relative P300 amplitude
in response to the critical items compared to the neutral items. CONCLUSION:
Noninvasive prefrontal cortex excitability disruption by rTMS can be used to
manipulate the sensitivity of ERP signatures of deception to critical items in a
concealment-based variant of lie detection test.
PMID- 28413708
TI - Neural evidence for phonologically based language production deficits in older
adults: An fMRI investigation of age-related differences in picture-word
interference.
AB - INTRODUCTION: Older adults often show declines in phonological aspects of
language production, particularly for low-frequency words, but maintain strong
semantic systems. However, there are different theories about the mechanism that
may underlie such age-related differences in language (e.g., age-related declines
in transmission of activation or inhibition). METHODS: This study used fMRI to
investigate whether age-related differences in language production are associated
with transmission deficits or inhibition deficits. We used the picture-word
interference paradigm to examine age-related differences in picture naming as a
function of both target frequency and the relationship between the target picture
and distractor word. RESULTS: We found that the presence of a categorically
related distractor led to greater semantic elaboration by older adults compared
to younger adults, as evidenced by older adults' increased recruitment of regions
including the left middle frontal gyrus and bilateral precuneus. When presented
with a phonologically related distractor, patterns of neural activation are
consistent with previously observed age deficits in phonological processing,
including age-related reductions in the recruitment of regions such as the left
middle temporal gyrus and right supramarginal gyrus. Lastly, older, but not
younger, adults show increased brain activation of the pre- and postcentral gyri
as a function of decreasing target frequency when target pictures are paired with
a phonological distractor, suggesting that cuing the phonology of the target
disproportionately aids production of low-frequency items. CONCLUSIONS: Overall,
this pattern of results is generally consistent with the transmission deficit
hypothesis, illustrating that links within the phonological system, but not the
semantic system, are weakened with age.
PMID- 28413710
TI - Combination of standard axial and thin-section coronal diffusion-weighted imaging
facilitates the diagnosis of brainstem infarction.
AB - BACKGROUND AND PURPOSE: Although diffusion-weighted imaging (DWI) is a very
sensitive technique for the detection of small ischemic lesions in the human
brain, in particular in the brainstem it may fail to demonstrate acute ischemic
infarction. In this study, we sought to evaluate the value of additional thin
section coronal DWI for the detection of brainstem infarction. METHODS: In 155
consecutive patients (median age 69 [interquartile range, IQR 57-78] years, 95
[61.3%] males) with isolated brainstem infarction, MRI findings were analyzed,
with emphasis on ischemic lesions on standard axial (5 mm) and thin-section
coronal (3 mm) DWI. RESULTS: On DWI, we identified ischemic lesions in the
mesencephalon in 12 (7.7%), pons in 115 (74.2%), and medulla oblongata in 31
(20%) patients. In 3 (1.9%) cases-all of these with medulla oblongata infarction
the ischemic lesion was detected only on thin-section coronal DWI. Overall, in 35
(22.6%) patients the ischemic lesion was more easily identified on thin-section
coronal DWI in comparison to standard axial DWI. In these, the ischemic lesions
were significantly smaller (0.06 [IQR 0.05-0.11] cm3 vs. 0.25 [IQR 0.13-0.47]
cm3; p < .001) in comparison to those patients whose ischemic lesion was more
easily (6 [3.9%]) or at least similarly well identified (114 [73.5%]) on standard
axial DWI. CONCLUSIONS: Since thin-section coronal DWI may facilitate the
diagnosis of brainstem infarction, we suggest its inclusion in standard stroke
MRI protocols.
PMID- 28413709
TI - Awareness, apathy, and depression in Alzheimer's disease and mild cognitive
impairment.
AB - INTRODUCTION: Results from studies on awareness disorders in Alzheimer's disease
(AD) are controversial because the methodologies, the "objects" of awareness, and
the patients' pathologic stage all vary. Our study aimed to compare scores and
correlates of awareness according to the stage of the disease and the assessment
method. METHODS: We compared 20 mild AD patients to 20 mild cognitive impairment
(MCI) patients, using the Patient Competency Rating Scale (PCRS; patient vs.
caregiver report) and the Self-Consciousness Scale (rating scale). All patients
underwent cognitive, psycho-affective and behavioral assessments (global
cognition, executive functions, episodic memory, anxiety-depression, and apathy
measures). RESULTS: Groups were matched for age, education, and gender. They were
comparable on the depression, anxiety, apathy and awareness scales (ps > .05),
and differed for all cognitive variables (p < .05). Using the median split
approach, greater apathy and lower depression were associated with poorer
awareness on the Self-Consciousness Scale (respectively: odds ratio [OR] = 4.8, p
= .03; OR = 4.84, p = .04), and the PCRS (only apathy: OR = 9.3, p = .003).
Greater apathy plus lower depression were associated with poorer awareness in
both scales (PCRS: OR = 40.5, p = .005; Self-consciousness scale: OR = 28, p =
.012). CONCLUSION: These results evidence comparable awareness between AD and MCI
patients. The correlates were more affective and behavioral than cognitive,
independently from assessment method.
PMID- 28413711
TI - High-throughput sequencing revealed a novel SETX mutation in a Hungarian patient
with amyotrophic lateral sclerosis.
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
characterized by the degeneration of the motor neurons. To date, 126 genes have
been implicated in ALS. Therefore, the heterogenous genetic background of ALS
requires comprehensive genetic investigative approaches. METHODS: In this study,
DNA from 28 Hungarian ALS patients was subjected to targeted high-throughput
sequencing of the coding regions of three Mendelian ALS genes: FUS, SETX, and
C9ORF72. RESULTS: A novel heterozygous missense mutation (c.791A>G, p.N264S) of
the SETX gene was identified in a female patient presenting an atypical ALS
phenotype, including adult onset and lower motor neuron impairment. No further
mutations were detected in the other Mendelian ALS genes investigated.
CONCLUSION: Our study contributes to the understanding of the genetic and
phenotypic diversity of motor neuron diseases (MNDs). Our results also suggest
that the elucidation of the genetic background of MNDs requires a complex
approach, including the screening of both Mendelian and non-Mendelian genes.
PMID- 28413712
TI - Variation within MBP gene predicts disease course in multiple sclerosis.
AB - OBJECTIVE: Prognosis following a first demyelinating event is difficult to
predict, with no genetic markers of MS progression currently identified. Myelin
basic protein (MBP) is a major component of the myelin sheath of CNS neurons and
may play a central role in demyelinating diseases such as MS. However, genetic
variation in MBP has not been implicated in MS onset risk in large genome-wide
association studies. We hypothesized that genetic variations in MBP may be a
determinant of MS clinical course. MATERIALS AND METHODS: We investigated whether
variations in the MBP gene altered clinical course (conversion to MS and/or
relapse, and annualized change in disability), using a prospectively collected
longitudinal cohort study of 127 persons who had had a first demyelinating event,
followed up to the 5-year review. RESULTS: We found one variant, rs12959006,
predicted worse clinical outcomes. The risk genotype (CT + TT) was significantly
associated with hazard of relapse (HR = 1.74, 95% CI = 1.19-2.56, p = .005) and
of greater annualized disability progression (beta = 0.18, 95% CI = 0.06-0.30, p
= .004). We also found a significant interaction between the risk genotype and
baseline anti-HHV6 IgG in predicting MS (pinteraction = 0.05) and relapse
(pinteraction = 0.02). Functional prediction analysis showed this variant is the
target of many transcription factors and the binding sites of miR-218 and miR-188
3p. CONCLUSIONS: Our results provide novel insights into the role of genetic
variation within the MBP gene predicting MS clinical course, both directly and by
interaction with known environmental MS risk factors.
PMID- 28413713
TI - Catastrophic outcome of patients with a rebound after Natalizumab treatment
discontinuation.
AB - INTRODUCTION: Natalizumab (NTZ) is an effective drug for the treatment of
relapsing-remitting multiple sclerosis. In some patients discontinuation is
mandatory due to the risk of progressive multifocal leukoencephalopathy. However,
severe clinical and radiological worsening has been described after drug
cessation. Our aim was to describe the clinical and radiological features of the
rebound phenomenon. MATERIAL AND METHODS: Patients switched from NTZ to
Fingolimod (FTY) who had presented a rebound after discontinuation were selected.
Clinical and magnetic resonance imaging (MRI) data were collected. RESULTS: Four
JC virus positive patients were included. The mean disease duration was 9.5 years
(SD: 4.12) with a mean time of 3.1 years on NTZ. All patients started FTY within
3-4 months. Neurological deterioration started in a mean time of 3.5 months (SD:
2.08) with multifocal involvement: 75% motor disturbances, 50% cognitive
impairment, 25% seizures. The average worsening in Expanded Disability Status
Scale [EDSS] was of 3.25 points (SD: 2.33). The MRI showed a very large increase
in T2 and gadolinium-enhanced lesions (mean: 23.67, SD: 18.58). All patients
received 5 days of IV methylprednisolone, one patient required plasma exchange.
All the patients presented neurological deterioration with an EDSS worsening of
1.13 points (SD: 0.48). After the rebound three patients continued treatment with
FTY, only one patient restarted NTZ. CONCLUSION: Discontinuation of NTZ treatment
may trigger a severe rebound with marked clinical and radiological worsening. A
very careful evaluation of benefit-risk should be considered before NTZ
withdrawal, and a close monitoring and a short washout period is recommended
after drug withdrawal.
PMID- 28413714
TI - Cerebrospinal fluid and plasma beta-endorphin levels in children with cerebral
malaria.
AB - OBJECTIVES: Cerebral malaria (CM) is the most lethal form of malaria, yet its
pathogenesis is not fully understood. Cytoadherence, sequestration, alterations
in cytokine expression, inflammation, and microvascular obstruction are all
hypothesized to be important in the aetio-pathogenesis of coma which
characterizes cerebral malaria and the death which sometimes result. Beta (beta)
endorphin has been postulated to be involved in the pathogenetic processes of
inflammation and cytokine expression, although the exact role is unknown. The aim
of this study was to determine the levels of beta-endorphin in cerebrospinal
fluid (CSF) and plasma of children with CM and compare the levels of beta
endorphin in the plasma of children with CM with that of apparently healthy age-
and sex-matched controls at Ile-Ife, Nigeria. MATERIALS AND METHODS: Additional
to the standard investigation for CM, CSF and venous blood samples were obtained
from the subjects for the determination of beta-endorphin levels. RESULTS: Forty
children with CM were studied along with forty age- and sex-matched controls. The
mean CSF beta-endorphin (+/- SD) level for the children with CM was 1.8 +/- 0.9
pmol/L. The mean plasma beta-endorphin levels at admission (3.1 +/- 2.0 pmol/L)
and discharge (4.1 +/- 3.3 pmol/L) were higher in children with CM than in the
control subjects (2.7 +/- 0.7 pmol/L). However, only the mean plasma beta
endorphin levels at discharge was significantly higher than that of controls (p =
.012). CONCLUSION: Children with CM had higher mean plasma beta-endorphin levels
compared to the controls and there was increased production of beta-endorphins in
children with CM during the course of the illness.
PMID- 28413715
TI - Brain serotonin 4 receptor binding is inversely associated with verbal memory
recall.
AB - BACKGROUND: We have previously identified an inverse relationship between
cerebral serotonin 4 receptor (5-HT 4R) binding and nonaffective episodic memory
in healthy individuals. Here, we investigate in a novel sample if the association
is related to affective components of memory, by examining the association
between cerebral 5-HT 4R binding and affective verbal memory recall. METHODS:
Twenty-four healthy volunteers were scanned with the 5-HT 4R radioligand
[11C]SB207145 and positron emission tomography, and were tested with the Verbal
Affective Memory Test-24. The association between 5-HT 4R binding and affective
verbal memory was evaluated using a linear latent variable structural equation
model. RESULTS: We observed a significant inverse association across all regions
between 5-HT 4R binding and affective verbal memory performances for positive (p
= 5.5 * 10-4) and neutral (p = .004) word recall, and an inverse but
nonsignificant association for negative (p = .07) word recall. Differences in the
associations with 5-HT 4R binding between word categories (i.e., positive,
negative, and neutral) did not reach statistical significance. CONCLUSION: Our
findings replicate our previous observation of a negative association between 5
HT 4R binding and memory performance in an independent cohort and provide novel
evidence linking 5-HT 4R binding, as a biomarker for synaptic 5-HT levels, to the
mnestic processing of positive and neutral word stimuli in healthy humans.
PMID- 28413716
TI - Data-driven regions of interest for longitudinal change in three variants of
frontotemporal lobar degeneration.
AB - INTRODUCTION: Longitudinal imaging of neurodegenerative disorders is a
potentially powerful biomarker for use in clinical trials. In Alzheimer's
disease, studies have demonstrated that empirically derived regions of interest
(ROIs) can provide more reliable measurement of disease progression compared with
anatomically defined ROIs. METHODS: We set out to derive ROIs with optimal effect
size for quantifying longitudinal change in a hypothetical clinical trial by
comparing atrophy rates in 44 patients with behavioral variant of frontotemporal
dementia (bvFTD), 30 with the semantic variant primary progressive aphasia
(svPPA), and 26 with the nonfluent variant PPA (nfvPPA) to atrophy in 97
cognitively healthy controls. RESULTS: The regions identified for each variant
were generally what would be expected from prior studies of frontotemporal lobar
degeneration (FTLD). Sample size estimates for detecting a 40% reduction in
annual rate of ROI atrophy varied substantially across groups, being 103 per arm
in bvFTD, 31 in nfvPPA, and 10 in svPPA, but in all groups were less than those
estimated for a priori ROIs and clinical measures. The variability in location of
peak regions of atrophy across individuals was highest in bvFTD and lowest in
svPPA, likely relating to the differences in effect size. CONCLUSIONS: These
findings suggest that, while cross-validated maps of change can improve
sensitivity to change in FTLD compared with a priori regions, the reliability of
these maps differs considerably across syndromes. Future studies can utilize
these maps to design clinical trials, and should try to identify factors
accounting for the variability in patterns of atrophy across individuals,
particularly those with bvFTD.
PMID- 28413717
TI - Advances of CD19-directed chimeric antigen receptor-modified T cells in
refractory/relapsed acute lymphoblastic leukemia.
AB - Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a
significant cause of cancer-associated morbidity and mortality for children and
adults. Developing novel and effective molecular-targeted approaches is thus a
major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one
of the most promising targeted immunotherapies, has drawn extensive attention and
resulted in multiple applications. According to published studies, CD19-directed
CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both
children and adults with refractory/relapsed ALL, much higher than that of
chemotherapy. However, the encouraging outcomes are often associated with
complications such as cytokine release syndrome (CRS), serious neurotoxicity, and
on-target off-tumor effect, which seriously impeded further clinical application
of CAR-T cells. Moreover, CAR-T therapy is typically associated with high relapse
rate. This article briefly reviews the manufacture technologies, the conditioning
regimens, the cell infusion doses, as well as the prevention and treatment
strategies of complications for CAR-T cell therapy.
PMID- 28413718
TI - Best Practices for Medication Utilization Evaluations in Postsurgical Pain
Management.
AB - PURPOSE: The purpose of this review is to provide guidance that aids in the
practical design, implementation, and analysis of medication use evaluations
(MUEs) for postsurgical pain management. SUMMARY: Clinicians have long employed
drug use evaluations or drug utilization reviews to ensure the safe and
appropriate use of medications in a hospital, medical practice, or other
healthcare setting. Although these approaches are valuable, there is a growing
trend toward replacing these methods with the MUE, a performance improvement tool
that focuses on assessing and improving medication use processes or medication
treatment response with the goal of optimizing patient outcomes. Utilizing MUEs
to assess patient outcomes and quality of life can be challenging in certain
therapeutic areas such as pain management, where measurements of pain can be
quantitative but are inherently subjective. Currently, there is little guidance
on the development of MUEs that balance subjective and objective outcomes.
CONCLUSION: MUEs continue to become the standard for quality improvement for
optimizing care and ensuring optimal outcomes. This review of the literature
provides guidance in post-surgical pain management, an area that requires
measurement of both subjective and objective outcomes.
PMID- 28413719
TI - Intra-specific variation and allometry of the skull of Late Cretaceous side
necked turtle Bauruemys elegans (Pleurodira, Podocnemididae) and how to deal with
morphometric data in fossil vertebrates.
AB - BACKGROUND: Previous quantitative studies on Bauruemys elegans (Suarez, 1969)
shell variation, as well as the taphonomic interpretation of its type locality,
have suggested that all specimens collected in this locality may have belonged to
the same population. We rely on this hypothesis in a morphometric study of the
skull. Also, we tentatively assessed the eating preference habits differentiation
that might be explained as due to ontogenetic changes. METHODS: We carried out an
ANOVA testing 29 linear measurements from 21 skulls of B. elegans taken by using
a caliper and through images, using the ImageJ software. First, a Principal
Components Analysis (PCA) was performed with 27 measurements (excluding total
length and width characters; =raw data) in order to visualize the scatter plots
based on the form variance only. Then, a second PCA was carried out using ratios
of length and width of each original measurement to assess shape variation among
individuals. Finally, original measurements were log-transformed to describe
allometries over ontogeny. RESULTS: No statistical differences were found between
caliper and ImageJ measurements. The first three PCs of the PCA with raw data
comprised 70.2% of the variance. PC1 was related to size variation and all others
related to shape variation. Two specimens plotted outside the 95% ellipse in
PC1~PC2 axes. The first three PCs of the PCA with ratios comprised 64% of the
variance. When considering PC1~PC2, all specimens plotted inside the 95% ellipse.
In allometric analysis, five measurements were positively allometric, 19 were
negatively allometric and three represented enantiometric allometry. Many bones
of the posterior and the lateral emarginations lengthen due to increasing size,
while jugal and the quadratojugal decrease in width. DISCUSSION: ImageJ is useful
in replacing caliper since there was no statistical differences. Yet iterative
imputation is more appropriate to deal with missing data in PCA. Some specimens
show small differences in form and shape. Form differences were interpreted as
occuring due to ontogeny, whereas shape differences are related to feeding
changes during growth. Moreover, all outlier specimens are crushed and/or
distorted, thus the form/shape differences may be partially due to taphonomy. The
allometric lengthening of the parietal, quadrate, squamosal, maxilla, associated
with the narrowing of jugal and quadratojugal may be related to changes in
feeding habit between different stages of development. This change in shape might
represent a progressive skull stretching and enlargement of posterior and lateral
emargination during ontogeny, and consequently, the increment of the feeding
apparatus musculature. Smaller individuals may have fed on softer diet, whereas
larger ones probably have had a harder diet, as seen in some living species of
Podocnemis. We conclude that the skull variation might be related to differences
in feeding habits over ontogeny in B. elegans.
PMID- 28413720
TI - Direct imaging of APP proteolysis in living cells.
AB - Alzheimer's disease is a multifactorial disorder caused by the interaction of
genetic, epigenetic and environmental factors. The formation of cytotoxic
oligomers consisting of Abeta peptide is widely accepted as being one of the main
key events triggering the development of Alzheimer's disease. Abeta peptide
production results from the specific proteolytic processing of the amyloid
precursor protein (APP). Deciphering the factors governing the activity of the
secretases responsible for the cleavage of APP is still a critical issue. Kits
available commercially measure the enzymatic activity of the secretases from
cells lysates, in vitro. By contrast, we have developed a prototypal rapid
bioassay that provides visible information on the proteolytic processing of APP
directly in living cells. APP was fused to a monomeric variant of the green
fluorescent protein and a monomeric variant of the red fluorescent protein at the
C-terminal and N-terminal (mChAPPmGFP), respectively. Changes in the proteolytic
processing rate in transfected human neuroblastoma and rat neuronal cells were
imaged with confocal microscopy as changes in the red/green fluorescence
intensity ratio. The significant decrease in the mean red/green ratio observed in
cells over-expressing the beta-secretase BACE1, or the alpha-secretase ADAM10,
fused to a monomeric blue fluorescent protein confirms that the proteolytic site
is still accessible. Specific siRNA was used to evaluate the contribution of
endogenous BACE1. Interestingly, we found that the degree of proteolytic
processing of APP is not completely homogeneous within the same single cell, and
that there is a high degree of variability between cells of the same type. We
were also able to follow with a fluorescence spectrometer the changes in the red
emission intensity of the extracellular medium when BACE1 was overexpressed. This
represents a complementary approach to fluorescence microscopy for rapidly
detecting changes in the proteolytic processing of APP in real time. In order to
allow the discrimination between the alpha- and the beta-secretase activity, we
have created a variant of mChAPPmGFP with a mutation that inhibits the alpha
secretase cleavage without perturbing the beta-secretase processing. Moreover, we
obtained a quantitatively robust estimate of the changes in the red/green ratio
for the above conditions by using a flow cytometer able to simultaneously excite
and measure the red and green fluorescence. Our novel approach lay the foundation
for a bioassay suitable to study the effect of drugs or particular conditions, to
investigate in an unbiased way the the proteolytic processing of APP in single
living cells in order, and to elucidate the causes of the variability and the
factors driving the processing of APP.
PMID- 28413721
TI - Aspects of gorgonopsian paleobiology and evolution: insights from the
basicranium, occiput, osseous labyrinth, vasculature, and neuroanatomy.
AB - Synapsida, the clade including therapsids and thus also mammals, is one of the
two major branches of amniotes. Organismal design, with modularity as a concept,
offers insights into the evolution of therapsids, a group that experienced
profound anatomical transformations throughout the past 270 Ma, eventually
leading to the evolution of the mammalian bauplan. However, the anatomy of some
therapsid groups remains obscure. Gorgonopsian braincase anatomy is poorly known
and many anatomical aspects of the brain, cranial nerves, vasculature, and
osseous labyrinth, remain unclear. We analyzed two gorgonopsian specimens,
GPIT/RE/7124 and GPIT/RE/7119, using propagation phase contrast synchrotron micro
computed tomography. The lack of fusion between many basicranial and occipital
bones in GPIT/RE/7124, which is an immature specimen, allowed us to reconstruct
its anatomy and ontogenetic sequence, in comparison with the mature GPIT/RE/7119,
in great detail. We explored the braincase and rendered various skull cavities.
Notably, we found that there is a separate ossification between what was
previously referred to as the "parasphenoid" and the basioccipital. We
reinterpreted this element as a posterior ossification of the basisphenoid: the
basipostsphenoid. Moreover, we show that the previously called "parasphenoid" is
in fact the co-ossification of the dermal parasphenoid and the endochondral
basipresphenoid. In line with previous descriptions, the anatomy of the osseous
labyrinth is rendered in detail, revealing a unique discoid morphology of the
horizontal semicircular canal, rather than toroidal, probably due to
architectural constraints of the ossification of the opisthotic and
supraoccipital. In addition, the orientation of the horizontal semicircular canal
suggests that gorgonopsians had an anteriorly tilted alert head posture. The
morphology of the brain endocast is in accordance with the more reptilian
endocast shape of other non-mammaliaform neotherapsids.
PMID- 28413722
TI - Performance of interferon-gamma release assay in the diagnosis of tuberculous
lymphadenitis: a meta-analysis.
AB - BACKGROUND: The diagnostic values of interferon-gamma release assays (IGRA) in
tuberculosis (TB) vary a lot with different site of infections, with especially
higher sensitivities in chronic forms of TB such as tuberculosis of the lymph
node. We conducted a meta-analysis to comprehensively evaluate the overall
accuracy of diagnostic IGRA for tuberculous lymphadenitis. METHODS: Pubmed, Web
of Science, EMBASE, Wanfang and CNKI databases up to February 17, 2017 were
searched to identify published studies. The study quality was evaluated using the
QUADAS-2 checklist. The pooled estimates of diagnostic parameters were generated
using a bivariate random-effects model and summary receiver operating
characteristic (SROC) curves were used to summarize global performance. RESULTS:
A total of ten qualified studies, performed in Korea or China, including 1,084
patients, were enrolled in this meta-analysis. The pooled estimates of diagnostic
accuracy were as follows: sensitivity, 0.89 (95% CI [0.85-0.92]); specificity,
0.81 (95% CI [0.77-0.83]); positive likelihood ratio (PLR), 4.25 (95% CI [2.79
6.47]); negative likelihood ratio (NLR), 0.16 (95% CI [0.12-0.22]); and area
under the curve (AUC) was 0.93. According to subgroup analyses, studies conducted
using QuantiFERON-TB, in Korean population and focusing on cervical lymphadenitis
exhibited relative higher specificity while lower sensitivity. No evidence of
publication bias was identified. CONCLUSIONS: IGRA exhibits high diagnostic
accuracy in tuberculous lymphadenitis. The diagnostic value of IGRA differed by
different IGRA methods, ethnicity and lymphadenitis location. Our conclusion may
be more applicable to population from TB prevalent areas.
PMID- 28413723
TI - Physiological effects of five different marine natural organic matters (NOMs) and
three different metals (Cu, Pb, Zn) on early life stages of the blue mussel
(Mytilus galloprovincialis).
AB - Metals are present in aquatic environments as a result of natural and
anthropogenic inputs, and may induce toxicity to organisms. One of the main
factors that influence this toxicity in fresh water is natural organic matter
(NOM) but all NOMs are not the same in this regard. In sea water, possible
protection by marine NOMs is not well understood. Thus, our study isolated marine
NOMs by solid-phase extraction from five different sites and characterized them
by excitation-emission fluorescence analysis-one inshore (terrigenous origin),
two offshore (autochthonous origin), and two intermediate in composition
(indicative of a mixed origin). The physiological effects of these five NOMS
alone (at 8 mg/L), of three metals alone (copper, lead and zinc at 6 ug Cu/L, 20
ug Pb/L, and 25 ug Zn/L respectively), and of each metal in combination with each
NOM, were evaluated in 48-h exposures of mussel larvae. Endpoints were whole body
Ca2++Mg2+-ATPase activity, carbonic anhydrase activity and lipid peroxidation. By
themselves, NOMs increased lipid peroxidation, Ca2++Mg2+-ATPase, and/or carbonic
anhydrase activities (significant in seven of 15 NOM-endpoint combinations),
whereas metals by themselves did not affect the first two endpoints, but Cu and
Pb increased carbonic anhydrase activities. In combination, the effects of NOMs
predominated, with the metal exerting no additional effect in 33 out of 45
combinations. While NOM effects varied amongst different isolates, there was no
clear pattern with respect to optical or chemical properties. When NOMs were
treated as a single source by data averaging, NOM had no effect on Ca2++Mg2+
ATPase activity but markedly stimulated carbonic anhydrase activity and lipid
peroxidation, and there were no additional effects of any metal. Our results
indicate that marine NOMs may have direct effects on this model marine organism,
as well as protective effects against metal toxicity, and the quality of marine
NOMs may be an important factor in these actions.
PMID- 28413724
TI - Are anti-ganglioside antibodies associated with proventricular dilatation disease
in birds?
AB - The identification of Parrot bornaviruses (PaBV) in psittacine birds with
proventricular dilatation disease (PDD) has not been sufficient to explain the
pathogenesis of this fatal disease, since not all infected birds develop clinical
signs. Although the most accepted theory indicates that PaBV directly triggers an
inflammatory response in this disease, another hypothesis suggests the disease is
triggered by autoantibodies targeting neuronal gangliosides, and PDD might
therefore resemble Guillain-Barre Syndrome (GBS) in its pathogenesis.
Experimental inoculation of pure gangliosides and brain-derived ganglioside
extracts were used in two different immunization studies. The first study was
performed on 17 healthy chickens (Gallus gallus domesticus): 11 chickens were
inoculated with a brain ganglioside extract in Freund's complete adjuvant (FCA)
and six chickens inoculated with phosphate-buffered saline. A second study was
performed five healthy quaker parrots (Myiopsitta monachus) that were divided
into three groups: Two quaker parrots received purified gangliosides in FCA, two
received a crude brain extract in FCA, and one control quaker parrot received FCA
alone. One chicken developed difficult in walking. Histologically, only a mild
perivascular and perineural lymphocytic infiltrate in the proventriculus. Two
quaker parrots (one from each treatment group) had mild lymphoplasmacytic
encephalitis and myelitis. However, none of the quaker parrots developed
myenteric ganglioneuritis, suggesting that autoantibodies against gangliosides in
birds are not associated with a condition resembling PDD.
PMID- 28413726
TI - gb4gv: a genome browser for geminivirus.
AB - BACKGROUND: Geminiviruses (family Geminiviridae) are prevalent plant viruses that
imperil agriculture globally, causing serious damage to the livelihood of
farmers, particularly in developing countries. The virus evolves rapidly,
attributing to its single-stranded genome propensity, resulting in worldwide
circulation of diverse and viable genomes. Genomics is a prominent approach taken
by researchers in elucidating the infectious mechanism of the virus. Currently,
the NCBI Viral Genome website is a popular repository of viral genomes that
conveniently provides researchers a centralized data source of genomic
information. However, unlike the genome of living organisms, viral genomes most
often maintain peculiar characteristics that fit into no single genome
architecture. By imposing a unified annotation scheme on the myriad of viral
genomes may downplay their hallmark features. For example, the viron of
begomoviruses prevailing in America encapsulates two similar-sized circular DNA
components and both are required for systemic infection of plants. However, the
bipartite components are kept separately in NCBI as individual genomes with no
explicit association in linking them. Thus, our goal is to build a comprehensive
Geminivirus genomics database, namely gb4gv, that not only preserves genomic
characteristics of the virus, but also supplements biologically relevant
annotations that help to interrogate this virus, for example, the targeted host,
putative iterons, siRNA targets, etc. METHODS: We have employed manual and
automatic methods to curate 508 genomes from four major genera of Geminiviridae,
and 161 associated satellites obtained from NCBI RefSeq and PubMed databases.
RESULTS: These data are available for free access without registration from our
website. Besides genomic content, our website provides visualization capability
inherited from UCSC Genome Browser. DISCUSSION: With the genomic information
readily accessible, we hope that our database will inspire researchers in gaining
a better understanding of the incredible degree of diversity of these viruses,
and of the complex relationships within and between the different genera in the
Geminiviridae. AVAILABILITY AND IMPLEMENTATION: The database can be found at:
http://gb4gv.lafayette.edu.
PMID- 28413725
TI - Trypanosoma cruzi reservoir-triatomine vector co-occurrence networks reveal meta
community effects by synanthropic mammals on geographic dispersal.
AB - Contemporary patterns of land use and global climate change are modifying
regional pools of parasite host species. The impact of host community changes on
human disease risk, however, is difficult to assess due to a lack of information
about zoonotic parasite host assemblages. We have used a recently developed
method to infer parasite-host interactions for Chagas Disease (CD) from vector
host co-occurrence networks. Vector-host networks were constructed to analyze
topological characteristics of the network and ecological traits of species'
nodes, which could provide information regarding parasite regional dispersal in
Mexico. Twenty-eight triatomine species (vectors) and 396 mammal species
(potential hosts) were included using a data-mining approach to develop models to
infer most-likely interactions. The final network contained 1,576 links which
were analyzed to calculate centrality, connectivity, and modularity. The model
predicted links of independently registered Trypanosoma cruzi hosts, which
correlated with the degree of parasite-vector co-occurrence. Wiring patterns
differed according to node location, while edge density was greater in
Neotropical as compared to Nearctic regions. Vectors with greatest public health
importance (i.e., Triatoma dimidiata, T. barberi, T. pallidipennis, T.
longipennis, etc), did not have stronger links with particular host species,
although they had a greater frequency of significant links. In contrast, hosts
classified as important based on network properties were synanthropic mammals.
The latter were the most common parasite hosts and are likely bridge species
between these communities, thereby integrating meta-community scenarios
beneficial for long-range parasite dispersal. This was particularly true for
rodents, >50% of species are synanthropic and more than 20% have been identified
as T. cruzi hosts. In addition to predicting potential host species using the co
occurrence networks, they reveal regions with greater expected parasite mobility.
The Neotropical region, which includes the Mexican south and southeast, and the
Transvolcanic belt, had greatest potential active T. cruzi dispersal, as well as
greatest edge density. This information could be directly applied for
stratification of transmission risk and to design and analyze human-infected
vector contact intervention efficacy.
PMID- 28413727
TI - A transdisciplinary approach to the initial validation of a single cell protein
as an alternative protein source for use in aquafeeds.
AB - The human population is growing and, globally, we must meet the challenge of
increased protein needs required to feed this population. Single cell proteins
(SCP), when coupled to aquaculture production, offer a means to ensure future
protein needs can be met without direct competition with food for people. To
demonstrate a given type of SCP has potential as a protein source for use in
aquaculture feed, a number of steps need to be validated including demonstrating
that the SCP is accepted by the species in question, leads to equivalent survival
and growth, does not result in illness or other maladies, is palatable to the
consumer, is cost effective to produce and can easily be incorporated into diets
using existing technology. Here we examine white shrimp (Litopenaeus vannamei)
growth and consumer taste preference, smallmouth grunt (Haemulon chrysargyreum)
growth, survival, health and gut microbiota, and Atlantic salmon (Salmo salar)
digestibility when fed diets that substitute the bacterium Methylobacterium
extorquens at a level of 30% (grunts), 100% (shrimp), or 55% (salmon) of the
fishmeal in a compound feed. In each of these tests, animals performed
equivalently when fed diets containing M. extorquens as when fed a standard
aquaculture diet. This transdisciplinary approach is a first validation of this
bacterium as a potential SCP protein substitute in aquafeeds. Given the ease to
produce this SCP through an aerobic fermentation process, the broad applicability
for use in aquaculture indicates the promise of M. extorquens in leading toward
greater food security in the future.
PMID- 28413729
TI - Elucidating the diet of the island flying fox (Pteropus hypomelanus) in
Peninsular Malaysia through Illumina Next-Generation Sequencing.
AB - There is an urgent need to identify and understand the ecosystem services of
pollination and seed dispersal provided by threatened mammals such as flying
foxes. The first step towards this is to obtain comprehensive data on their diet.
However, the volant and nocturnal nature of bats presents a particularly
challenging situation, and conventional microhistological approaches to studying
their diet can be laborious and time-consuming, and provide incomplete
information. We used Illumina Next-Generation Sequencing (NGS) as a novel, non
invasive method for analysing the diet of the island flying fox (Pteropus
hypomelanus) on Tioman Island, Peninsular Malaysia. Through DNA metabarcoding of
plants in flying fox droppings, using primers targeting the rbcL gene, we
identified at least 29 Operationally Taxonomic Units (OTUs) comprising the diet
of this giant pteropodid. OTU sequences matched at least four genera and 14 plant
families from online reference databases based on a conservative Least Common
Ancestor approach, and eight species from our site-specific plant reference
collection. NGS was just as successful as conventional microhistological analysis
in detecting plant taxa from droppings, but also uncovered six additional plant
taxa. The island flying fox's diet appeared to be dominated by figs (Ficus sp.),
which was the most abundant plant taxon detected in the droppings every single
month. Our study has shown that NGS can add value to the conventional
microhistological approach in identifying food plant species from flying fox
droppings. At this point in time, more accurate genus- and species-level
identification of OTUs not only requires support from databases with more
representative sequences of relevant plant DNA, but probably necessitates in situ
collection of plant specimens to create a reference collection. Although this
method cannot be used to quantify true abundance or proportion of plant species,
nor plant parts consumed, it ultimately provides a very important first step
towards identifying plant taxa and spatio-temporal patterns in flying fox diets.
PMID- 28413728
TI - Mechanism of endothelial nitric oxide synthase phosphorylation and activation by
tentacle extract from the jellyfish Cyanea capillata.
AB - Our previous study demonstrated that tentacle extract (TE) from the jellyfish
Cyanea capillata (C. capillata) could cause a weak relaxation response mediated
by nitric oxide (NO) using isolated aorta rings. However, the intracellular
mechanisms of TE-induced vasodilation remain unclear. Thus, this study was
conducted to examine the role of TE on Akt/eNOS/NO and Ca2+ signaling pathways in
human umbilical vein endothelial cells (HUVECs). Our results showed that TE
induced dose- and time-dependent increases of eNOS activity and NO production.
And TE also induced Akt and eNOS phosphorylation in HUVECs. However, treatment
with specific PI3-kinase inhibitor (Wortmannin) significantly inhibited the
increases in NO production and Akt/eNOS phosphorylation. In addition, TE also
stimulated an increase in the intracellular Ca2+ concentration ([Ca2+]i), which
was significantly attenuated by either IP3 receptor blocker (Heparin) or PKC
inhibitor (PKC 412). In contrast, extracellular Ca2+-free, L-type calcium channel
blocker (Nifedipine), or PKA inhibitor (H89) had no influence on the [Ca2+]i
elevation. Since calcium ions also play a critical role in stimulating eNOS
activity, we next explored the role of Ca2+ in TE-induced Akt/eNOS activation. In
consistent with the attenuation of [Ca2+]i elevation, we found that Akt/eNOS
phosphorylation was also dramatically decreased by Heparin or PKC 412, but not
affected by Nifedipine or H89. However, the phosphorylation level could also be
decreased by the removal of extracellular calcium. Taken together, our findings
indicated that TE-induced eNOS phosphorylation and activation were mainly through
PI3K/Akt-dependent, PKC/IP3R-sensitive and Ca2+-dependent pathways.
PMID- 28413730
TI - Effects of chronic exposure to clothianidin on the earthworm Lumbricus
terrestris.
AB - Although neonicotinoids are targeted at insects, their predominant use as a seed
dressing and their long persistence in soils mean that non-target soil organisms
such as earthworms are likely to be chronically exposed to them. Chronic exposure
may pose risks that are not evaluated in most toxicity tests. We experimentally
tested the effect of field-realistic concentrations of a commonly used
neonicotinoid, clothianidin, on mortality, weight gain, and food consumption to
assess the impacts of chronic exposure over four months on fitness of L.
terrestris individuals. We undertook three separate experiments, each with
different exposure routes: treated soil only (experiment A), treated food and
soil combined (experiment B) and treated food only (experiment C). Mortality was
negatively affected by exposure from treated soil only with greatest mortality
observed in the groups exposed to the two highest concentrations (20 ppb and 100
ppb), but no clear effect on mortality was found in the other two experiments.
When clothianidin was present in the food, an anti-feedant effect was present in
months one and two which subsequently disappeared; if this occurs in the field,
it could result in reduced rates of decomposition of treated crop foliage. We
found no significant effects of any treatment on worm body mass. We cannot rule
out stronger adverse effects if worms come into close proximity to treated seeds,
or if other aspects of fitness were examined. Overall, our data suggest that
field-realistic exposure to clothianidin has a significant but temporary effect
on food consumption and can have weak but significant impacts on mortality of L.
terrestris.
PMID- 28413731
TI - Meloxicam ameliorates the cartilage and subchondral bone deterioration in
monoiodoacetate-induced rat osteoarthritis.
AB - OBJECTIVE: This study aimed to quantify the cartilage- and subchondral bone
related effects of low-dose and high-dose meloxicam treatment in the late phase
of mono-iodoacetate-induced osteoarthritis of the stifle. METHODS: Thirty-four
male Wistar rats received intra-articular injection of mono-iodoacetate to
trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono
iodoacetate-injected rats were assigned to three groups and treated from week 4
to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg,
n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4
additional weeks (end of week 11) the animals were sacrificed, and the stifle
joints were examined histologically and immunohistochemically for cyclooxygenase
2, in conformity with recommendations of the Osteoarthritis Research Society
International. Serum cytokines IL-6, TNFalpha and IL-10 were measured at the end
of weeks 3, 7, and 11. RESULTS: Compared with saline-treated controls, animals
treated with mono-iodoacetate developed various degrees of osteoarthritis. The
cartilage degeneration score and the total cartilage degeneration width were
significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose
(p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In
the subchondral bone, only high-dose meloxicam exerted a significant protective
effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated
animals was abolished in both meloxicam groups. Increase with borderline
significance of TNFalpha in GrpP from week 3 to week 7 (p = 0.049) and reduction
of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed. CONCLUSION:
In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a
chondroprotective effect, and the high dose also protected against subchondral
bone lesions. The results suggest a superior protection of the high-dose
meloxicam arresting the low-grade inflammatory pathway accompanied by chronic
cartilage deterioration.
PMID- 28413732
TI - Calcification and growth rate recovery of the reef-building Pocillopora species
in the northeast tropical Pacific following an ENSO disturbance.
AB - Pocilloporids are one of the major reef-building corals in the eastern tropical
Pacific (ETP) and also the most affected by thermal stress events, mainly those
associated with El Nino/Southern Oscillation (ENSO) periods. To date, coral
growth parameters have been poorly reported in Pocillopora species in the
northeastern region of the tropical Pacific. Monthly and annual growth rates of
the three most abundant morphospecies (P. cf. verrucosa, P. cf. capitata, and P.
cf. damicornis) were evaluated during two annual periods at a site on the Pacific
coast of Mexico. The first annual period, 2010-2011 was considered a strong
ENSO/La Nina period with cool sea surface temperatures, then followed by a non
ENSO period in 2012-2013. The linear extension rate, skeletal density, and
calcification rate averaged (+/-SD) were 2.31 +/- 0.11 cm yr-1, 1.65 +/- 0.18 g
cm-3, 5.03 +/- 0.84 g cm-2 yr-1 respectively, during the strong ENSO event. In
contrast, the respective non-ENSO values were 3.50 +/- 0.64 cm yr-1, 1.70 +/-
0.18 g cm-3, and 6.02 +/- 1.36 g cm-2 yr-1. This corresponds to 52% and 20%
faster linear extension and calcification rates, respectively, during non-ENSO
period. The evidence suggests that Pocillopora branching species responded
positively with faster growth rates following thermal anomalies, which allow them
to maintain coral communities in the region.
PMID- 28413733
TI - Experimental Studies on the Hydrotreatment of Kraft Lignin to Aromatics and
Alkylphenolics Using Economically Viable Fe-Based Catalysts.
AB - Limonite, a low-cost iron ore, was investigated as a potential hydrotreatment
catalyst for kraft lignin without the use of an external solvent (batch reactor,
initial H2 pressure of 100 bar, 4 h). The best results were obtained at 450
degrees C resulting in 34 wt % of liquefied kraft lignin (lignin oil) on lignin
intake. The composition of the lignin oil was determined in detail (elemental
composition, GC-MS, GC*GC-FID, and GPC). The total GC-detectable monomeric
species amounts up to 31 wt % on lignin intake, indicating that 92 wt % of the
products in the lignin oil are volatile and thus of low molecular weight. The
lignin oil was rich in low-molecular-weight alkylphenolics (17 wt % on lignin)
and aromatics (8 wt % on lignin). Performance of the limonite catalyst was
compared to other Fe-based catalysts (goethite and iron disulfide) and limonite
was shown to give the highest yields of alkylphenolics and aromatics. The
limonite catalyst before and after reaction was characterized using XRD, TEM, and
nitrogen physisorption to determine changes in structure during reaction.
Catalyst recycling tests were performed and show that the catalyst is active
after reuse, despite the fact that the morphology changed and that the surface
area of the catalyst particles was decreased. Our results clearly reveal that
cheap limonite catalysts have the potential to be used for the
depolymerization/hydrodeoxygenation of kraft lignin for the production of
valuable biobased phenolics and aromatics.
PMID- 28413734
TI - Implantable Systems for Continuous Liquorpheresis and CSF Replacement.
AB - Liquorpheresis (cerebrospinal fluid filtration) comprises a therapeutical
approach that has been proposed to treat several neurological conditions where
antibodies, inflammatory mediators, or abnormal peptides are the cause or play an
important role in the pathogenesis of the disease. Continuous or intermittent
cerebrospinal fluid (CSF) replacement may be an alternative approach not explored
thus far. Here, we review previous experiences in the use of liquorpheresis in
autoimmune and degenerative neurological diseases. Then we describe previous
technical reports and provide some new innovations in order to design
bidirectional CSF shunting systems that can be complemented either with a deposit
of artificial CSF or with a filter of CSF, allowing CSF replacement or
liquorpheresis respectively. Both options would lead to mechanical dilution of
the patient's CSF.
PMID- 28413735
TI - A Survey of Handwashing Knowledge and Attitudes among the Healthcare
Professionals in Lahore, Pakistan.
AB - OBJECTIVE: To evaluate the knowledge and attitudes towards handwashing of
clinical year medical and dental students and health-care professionals (HCPs)
working in the departments of medicine, surgery, dentistry, nursing, and
physiotherapy in Lahore, Pakistan. METHODOLOGY: This was a cross-sectional survey
conducted during May and June 2016. After approval from the institutional review
board, a modified form of the World Health Organization (WHO) Hand Hygiene
Knowledge Questionnaire for Healthcare workers that included 18 items was sent to
400 clinical year students and HCPs from six medical colleges and affiliated
hospitals of Lahore. The data obtained was entered and analyzed by using IBM SPSS
version 20 (IBM, NY, USA). Chi-square was used as the test of significance. A p
value of <0.05 was considered statistically significant for all purposes.
RESULTS: The response rate was 79%. Less than half of the respondents (149,
47.9%) were satisfied with their knowledge regarding hand hygiene. Statistically
significant associations of various groups of HCPs were observed with their
satisfaction regarding knowledge about hand hygiene (p-value = 0.022), their
awareness of the proper technique required for handwashing proposed by the WHO (p
value = 0.001), and their awareness about other preventive techniques proposed by
the WHO and Centers for Disease Control (CDC) (p-value = 0.021). CONCLUSIONS: The
majority of the clinical year students and HCPs were not satisfied with their
knowledge regarding hand hygiene. HCPs working in different departments have
varying knowledge and attitudes towards hand hygiene. Females were found to be
more satisfied with their handwashing practices. Teaching proper technique of
handwashing to medical students and starting refresher courses regarding hand
hygiene for HCPs are dire needs. The WHO-recommended guidelines should not only
be taught but also implemented in the medical field as poor hand hygiene
techniques have led to the spread of many diseases around the globe.
PMID- 28413736
TI - Targeted Intraspinal Radiofrequency Ablation for Lumbar Spinal Stenosis.
AB - INTRODUCTION: By using a combination of magnetic resonance imaging (MRI) and
computed tomography (CT) of the lumbar spine, it is possible to distinguish
between spinal stenosis caused by bone compression and specific soft tissue
epidural intraspinal lesions that cause localized spinal canal stenosis and
neural compression. Examples include facet cysts and yellow ligament hypertrophy.
Many of these patients are elderly with medical comorbidities that make open
surgery problematic. MATERIALS & METHODS: This is a study of patients with
predominantly soft tissue stenosis being treated with targeted intraspinal
radiofrequency (RF) heat ablation. This novel procedure is performed under local
anesthesia in an outpatient setting using intra-operative imaging. Fine tip 20
gauge RF electrodes (Stryker(r) PA, USA) are precisely placed under radiologic
guidance in the identified soft tissue causing the posterior compression of the
lumbar spinal canal. After sensory and motor testing to make sure there is a safe
distance of the needle tip from the nearby nerve roots to avoid any neural
effect, multiple targeted lesions correlated by the MRI or CT scan are made in
the fibrous and cystic soft tissue. Lesions are created using a focused 2 or 5 mm
tip at 60 degrees centigrade ( degrees C) for either 30 or 60 seconds. This heat
causes sufficient shrinking of the targeted soft tissue resulting in relative
reduction of the soft tissue component of the stenosis. This relative reduction
in the stenosis of the spinal canal, similar to that measured with interspinous
devices, provides long-term relief of symptoms, signs, and improvement of spinal
motion in patients with lumbar stenosis. This report will review the spinal
anatomy, and development and history of using RF in and around the nerve roots
and epidural space, as it relates to lumbar stenosis. Examples of before and
after MRI scans demonstrate the radiologic reduction in the size of the lesions.
This soft tissue reduction correlates with patients' improvement in pain and
clinical symptoms. Follow-up of the patients up to 30 months shows that the
effect of RF heat on the soft tissue is long lasting. RESULTS: In our long-term
follow-up of greater than six months, 58% of RF treated patients had lasting
relief of clinical symptoms, back pain, and claudication with increased spinal
movement. This reduction in pain and improvement in motion allows patients to
continue more aggressive physical therapy and muscle strengthening that
secondarily can improve their symptoms. Post-procedure follow-up MRI scans in
multiple patients have shown a clear reduction in soft tissue lesion size. Long
term follow-up demonstrated that 58% of patients treated with RF targeted
ablation have not required further intervention and 22% went on to other surgical
treatments for lumbar spinal stenosis. CONCLUSION: By reducing the soft tissue
component of the stenosis with RF ablation and creating relatively more epidural
space, targeted intraspinal RF may be a possible minimally invasive, percutaneous
non-surgical alternative to treatment in a number of patients where soft tissue
lumbar stenosis is the main cause of patients' symptoms. This technique offers a
simple and safe additional method to relieve symptoms of lumbar stenosis and
possibly compression within the neural foramina, especially in the elderly.
PMID- 28413737
TI - Amino Acid (Leucine) Chromatography: A Study of Branched-Chain Aminoaciduria in
Type 2 Diabetes.
AB - INTRODUCTION: Diabetes is a disease characterized by insulin deficiency resulting
in glucose intolerance and in abnormalities of other metabolic fuels including
protein. Recently, a number of studies have revealed that branched-chain amino
acids (BCAAs) (leucine, isoleucine, and valine) play an important role in the
regulation of protein synthesis by activating mammalian target of rapamycin
(mTOR) in pancreatic beta cells. BCAAs have positive effects on the regulation of
glucose homeostasis. Leucine is an important nutrient signal as evidenced by
recent observations, which showed increased fasting concentrations of circulating
BCAAs being associated with an increased risk of type 2 diabetes (T2D) and
insulin resistance in humans. Leucine seems to have direct effects on
hypothalamic and brainstem functioning involved in satiety, which can potentially
contribute to obesity and T2D. A number of observational studies indicate that
elevated activity of BCAAs could be associated with poor metabolic health and T2D
complications. Although these associations were consistently observed in humans,
the mechanisms underlying this relationship remain to be completely understood.
In this study, we have attempted to evaluate urinary excretion of leucine among
patients of T2D and compared them with healthy controls by using a low-cost and
non-invasive amino acid chromatography technique. METHODS: The study was carried
out in the Department of Biochemistry, Central Research Unit, Prathima Institute
of Medical Sciences (PIMS), Karimnagar, Telangana, India, during the period
between July and September 2016. A group of 55 normal healthy subjects (control
group A), and 55 patients suffering from T2D on treatment (test group B), were
enrolled in the study. The urine samples were collected from normal and T2D
subjects. Thin-layer chromatography (TLC) for leucine was performed on all the
urine samples. RESULTS: A strong correlation (p=0.0004) was found between the
urinary excretion of leucine among the control (Rf=0.174 +/-0.089) and T2D
(Rf=0.247 +/-0.030) patients. CONCLUSION: Excretion of BCAAs (leucine) in
detectable and increased quantities reflect the presence of an altered metabolic
state attributable to T2D, which in turn could lead to early diabetic
complications. This method (TLC), being non-invasive and cost-effective, could be
recommended for assessing the progression and management of type 2 diabetes
patients.
PMID- 28413738
TI - High-energy Trauma Precipitating Intramedullary Cavernous Malformation Hemorrhage
- A Possible Underreported Mechanism.
AB - Cavernous malformations are uncommon vascular lesions with an estimated
prevalence of 0.5% in the general population. Intramedullary cavernous
malformations (ICM) represent a rare subset of lesions, which account for
approximately 5% of all cavernous malformations. The annual risk of hemorrhage in
ICMs has been reported to range from 1.4 to 6.8%. Most patients are diagnosed
with neurological dysfunction secondary to ICM hemorrhage and little is known
about the inciting events that lead to hemorrhage. A few studies have suggested
that minor and major trauma or even intense exertion may increase the risk of
hemorrhage. We report the case of a 62-year-old male who developed progressive
neurological deterioration following a motor vehicle accident. During work-up, an
ICM was found at T4 and was surgically removed. At his 10-month follow-up, the
patient had partially recovered, regaining motor strength in his right lower
extremity, but had a persistent decrease in temperature and pinprick sensation on
the left side starting at the T6 dermatome. We hypothesize that ICMs can rupture
after high-energy impacts, such as the motor vehicle accident in our patient, and
mechanical factors, such as trauma and stretching maneuvers, can play a role in
the pathogenesis of ICM hemorrhage.
PMID- 28413739
TI - Genetic Modulation Therapy Through Stem Cell Transplantation for Human
Immunodeficiency Virus 1 Infection.
AB - Highly active anti-retroviral treatment has changed the dimensions of the
outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired
immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment
which is spreading throughout the world extensively. Given the confinements of
the present restorative methodologies and the non-availability of any strategic
vaccination against HIV, there is a squeezing need to build a therapeutic
treatment. Viral tropism for HIV includes CD4+ cells, macrophages, and microglial
cells, and it is through binding with co-receptors C-C chemokine receptor type 5
(CCR5) and C-X-C chemokine receptor type 4 (CXCR4). While these cell types are
present in all individuals, there are rare cases that stayed uninfected even
after getting exposed to an overwhelming load of HIV. Research revealed a
homozygous 32-base pair deletion (Delta32/Delta32) in CCR5. After careful
consideration, a hypothesis was proposed a few years back that a cure for HIV
disease is possible, through hematopoietic stem cells transplantation from a
donor homozygous for the CCR5-Delta32 deletion. Hematopoietic stem cell (HSC)
based quality treatment may serve as a promising tool as these perpetual, self
renewing progenitor cells could be modified to oppose HIV infection. If done
properly, the changed HSCs would offer the permanent creation of genetically
modified cells that are resistant to HIV infection and/or have improved hostility
to viral action which will eventually clear the contaminated cells. The purpose
of this review is to concentrate on two facets of HSC genetic treatment for
potentially life-threatening HIV infection: building HIV-resistant cells and
designing cells that can target HIV disease. These two strategic approaches can
be the frontline of a quality treatment plan against HIV infection and, as an
individual treatment or a combination thereof, has been proposed to possibly
destroy HIV altogether.
PMID- 28413741
TI - Serial Magnetic Resonance Imaging in Creutzfeldt-Jakob Disease: a Case Report and
Literature Review.
AB - Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain
disorder. CJD usually appears in later life and runs a rapid course. Typically,
the onset of symptoms occurs about age 60 and about 90% of individuals die within
one year. We report a case of 67-year-old male presented with progressive
aphasia, confusion, dysphagia and inability to carry out activities of daily life
(ADLs) over a period of three to four weeks. The patient had past medical history
of chronic atrial fibrillation and hypertension. Prior to admission, the patient
was treated for ischemic stroke of left basal ganglia but continued to have
worsening encephalopathy. The spinal tap revealed a 14-3-3 protein level of
thirteen times the upper limit of normal; electroencephalogram (EEG) showed a
diffuse slowing of the background and periodic sharp waves with greater
involvement of the left hemisphere. Diffusion-weighted imaging (DWI) magnetic
resonance imaging (MRI) at the time of admission showed extensive signal
abnormality in the basal ganglia bilaterally and in the cerebral cortex
bilaterally, particularly over the left cerebral hemisphere. The persistence of
the MRI findings over several weeks was concerning for spongiform encephalopathy.
The probable diagnosis of Creutzfeldt-Jakob disease was made based on these
imaging findings taken together with the patient's clinical signs and symptoms of
a rapidly progressive encephalopathy. The patient was able to have some quality
time with his family as the diagnosis was made earlier than perhaps otherwise and
expired peacefully after comfort care measures were chosen. Serial MRI may serve
as a clue to the early diagnosis of CJD and potentially provide a better quality
of life for the patients.
PMID- 28413740
TI - Relationship of the Median and Radial Nerves at the Elbow: Application to
Avoiding Injury During Venipuncture or Other Invasive Procedures of the Cubital
Fossa.
AB - INTRODUCTION: The median and radial nerves are two important neural structures
found in the cubital fossa. The trajectory and landmarks used to identify their
location are important when procedures are done in this area. METHODS AND
MATERIALS: Ten fresh-frozen cadavers were dissected (20 upper limbs) and
measurements were taken from the medial epicondyle to the median and radial
nerves as well as to the lateral epicondyle of each limb. RESULTS: The distance
between the medial epicondyle and the median nerve was found to be three
centimeters with a range of 2.1 to four centimeters and the distance from the
medial epicondyle to the radial nerve had a mean distance of 5.5 cm and a range
of 3.8 to seven centimeters. DISCUSSION: Damage to the median or radial nerves
can lead to major complications including loss of extension, flexion, and
sensation in the forearm and hand. Other studies have tried to identify the
course of these nerves in order to prevent their injury during procedures.
CONCLUSION: After identifying the medial epicondyle, using the results we
obtained, physicians may have a better understanding of where the median and
radial nerves lie within the cubital fossa when performing procedures in this
area.
PMID- 28413742
TI - Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute
Leukemia.
AB - Myelodysplastic syndrome (MDS) refers to a group of various stem cell disorders,
characterized by dysplastic and ineffective production in one or more cell lines.
In general, MDS tends to present slowly over months to years and is commonly
detected with routine bloodwork by primary care physicians. Patients may be
asymptomatic and depending on age, comorbidities and risk classification of MDS
may not require aggressive therapy. However, MDS carries the risk of progressing
to acute leukemia over time. We present a case of rapidly progressive MDS in a
previously healthy middle-aged female, originally presenting and treated as acute
leukemia.
PMID- 28413743
TI - Real-Time Fluoroscopic and C-Arm Computed Tomography Evaluation of Ommaya
Reservoir Integrity.
AB - We describe a case of a 24-year-old patient with relapsed acute myelogenous
leukemia involving the central nervous system. After placement of an Ommaya
reservoir for intrathecal chemotherapy administration, the patient developed
progressive headache, nausea, and drowsiness and was found to have an enlarging
subdural collection underlying the Ommaya. To exclude leakage of the Ommaya
system into the subdural space, real-time fluoroscopic and C-arm computed
tomographic evaluation of the Ommaya reservoir was performed after iodinated
contrast injection into the reservoir. This novel technique demonstrated complete
integrity of the Ommaya reservoir without evidence of blockage or leakage of the
system. The patient underwent uncomplicated evacuation of the subdural collection
without replacement of the Ommaya reservoir and made an excellent recovery. This
technique for real-time interrogation of the Ommaya reservoir may have additional
utility in the evaluation for Ommaya reservoir dysfunction.
PMID- 28413744
TI - Bilateral Retinal Detachments Associated with Inversion Table Therapy.
AB - To report a case of sequential bilateral inferior retinal detachments secondary
to inversion table therapy. A 67-year-old-male developed inferior rhegmatoegnous
retinal detachments (RRD) in both eyes on two different occasions with the use of
inversion therapeutic tables. Various predisposing factors have been documented
for RRD such as previous cataract surgery, peripheral retinal degenerations, high
myopia, history of previous retinal detachments and direct ocular trauma. The
authors report here a case of inferior retinal detachments associated with the
use of inversion therapy. Physical therapists, physical medicine rehabilitation
physicians, and retinal specialists need be aware of this potential complication.
PMID- 28413746
TI - Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective
Matrix Metalloproteinase Inhibitor.
AB - Invited for this month's cover picture is the group of Professor Rainer Riedl
from the Institute of Chemistry and Biotechnology at the Zurich University of
Applied Sciences (ZHAW), Switzerland. The cover picture depicts the structure
based design of a drug-like small molecule inhibitor of matrix metalloproteinase
13 (MMP-13) with a combined dual binding motif. The targeted introduction of a
single fluoro atom was of vital importance for the optimization of the inhibitor.
For more details, read the full text of the Communication at
10.1002/open.201600158.
PMID- 28413745
TI - Seven Cases of Zika Virus Infection in South Florida.
AB - INTRODUCTION: Zika virus, an arbovirus of the Flaviviridae family, is a mosquito
borne virus known to cause microcephaly through vertical transmission. Infection
presents with mild, self-limiting symptoms. Currently, a Zika virus outbreak has
spread across most of South and Central America. Travel-related and sexually
transmitted cases have been reported across the United States. However, the
vector-borne transmission has been limited to Florida and Texas. We present seven
cases of Zika virus infection that presented at a single institution in South
Florida. METHODS: Patients were included that had real-time polymerase-chain
reaction (RT-PCR) for Zika virus RNA in urine or serum or enzyme-linked
immunosorbent assay (ELISA) for Immunoglobulin M (IgM) antibody against Zika
virus in serum. RESULTS: All seven patients reported recent travel or employment
in areas of active Zika virus transmission and at least two of the four most
commonly reported symptoms (fever, arthralgia, rash, and conjunctivitis) with a
rash present in all patients. All patients had positive RT-PCR for Zika virus RNA
in urine. RT-PCR for Zika virus RNA in serum was negative in four of five
patients that were tested, indicating that these patients likely presented one to
two weeks after symptom onset. CONCLUSION: The future of Zika virus outbreaks in
other cities in the United States is still uncertain. However, it is clear that
prevention and control policies are urgently needed. We have presented seven
confirmed cases of Zika virus infection in South Florida. In addition to
conducting research concerning both the diagnostic and therapeutic aspects of the
virus, there is a need for public awareness of its presentation, methods of
transmission, and subsequent clinical outcomes.
PMID- 28413747
TI - Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry.
AB - Tetrahydropyranyl (Thp) is recognized as a useful protecting group for alcohols
in organic synthesis. It has several advantages, including low cost, ease of
introduction, general stability to most non-acidic reagents, it confers good
solubility, and the ease with which it can be removed if the functional group it
protects requires manipulation. However, little attention has been paid to Thp in
peptide chemistry. Provided here is a concise analysis of the Thp protection of
various amino acid functionalities (OH, SH, NH and COOH) and its application to
peptide synthesis. Thp is a useful moiety for the side-chain protection of
serine, threonine and cysteine and is suitable for the Fmoc/tBu solid-phase
peptide synthesis strategy. The immobilized version of 3,4-dihydro-2H-pyran, the
so-called Ellman resin, is also discussed as a useful solid support for anchoring
the side chains of serine, threonine and tryptophan residues.
PMID- 28413749
TI - Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective
Matrix Metalloproteinase Inhibitor.
AB - The incorporation of fluorine atoms into functional molecules is of wide interest
in synthetic organic chemistry as well as cognate disciplines. In particular, in
medicinal chemistry, there is a strong desire to positively influence the
physicochemical molecular properties of drug compounds by introducing fluorine
into biologically active molecules. Here, we present targeted fluoro positioning
as the key design principle of converting a weak matrix metalloproteinase-13 (MMP
13) inhibitor into a very potent (IC50=6 nm) and highly selective (selectivity
factors of >1000 over MMP-1, 2, 3, 7, 8, 9, 10, 12, 14) inhibitor with excellent
plasma and microsomal stability, and no binding to the hERG channel (hERG: human
ether-a-go-go related gene).
PMID- 28413748
TI - Thiamine Assays-Advances, Challenges, and Caveats.
AB - Thiamine (vitamin B1) is essential to the health of all living organisms and
deficiency has long been associated with diseases in animals such as fish, birds,
alligators, and domesticated ruminant mammals. Thiamine is also implicated in
several human diseases including Alzheimer's, diabetes, dementia, depression and,
most notably, Wernicke-Korsakoff syndrome and Beriberi disease. Yet, highly
sensitive and specific detection of thiamine remains an analytical challenge, as
pM to nm levels of thiamine need to be detected in environmental and human
samples, respectively, various phosphorylated variants need to be discriminated,
and rapid on-site detection would be highly desirable. Furthermore, appropriate
sample preparation is mandatory, owing to the complexity of the relevant sample
matrices including fish tissues, ocean water, and body fluids. This Review has
two objectives. First, it provides a thorough overview of analytical techniques
published for thiamine detection over the last 15 years. Second, it describes the
principles of analytical approaches that are based on biorecognition and may open
up new avenues for rapid and high-throughput thiamine analysis. Most notably,
periplasmic binding proteins, ribozymes, and aptamers are of particular interest,
as they function as bioaffinity recognition elements that can fill an important
assay technology gap, owing to the unavailability of thiamine-specific commercial
antibodies. Finally, the authors provide brief evaluations of key outcomes of the
major assay concepts and suggest how innovative techniques could help develop
sensitive and specific thiamine analytical test systems.
PMID- 28413750
TI - An Optically Isotropic Antiferroelectric Liquid Crystal (OI-AFLC) Display Mode
Operating over a Wide Temperature Range using Ternary Bent-Core Liquid Crystal
Mixtures.
AB - We report on the synthesis and characterization of bent-core liquid crystal (LC)
compounds and the preparation of mixtures that provide an optically isotropic
antiferroelectric (OI-AFLC) liquid crystal display mode over a very wide
temperature interval and well below room temperature. From the collection of
compounds synthesized during this study, we recognized that several ternary
mixtures displayed a modulated SmCaPA phase down to below -40 degrees C and up
to about 100 degrees C on both heating and cooling, as well as optical tilt
angles in the transformed state of approximately 45 degrees (optically isotropic
state). The materials were fully characterized and their liquid crystal as well
as electro-optical properties analyzed by polarized optical microscopy,
differential scanning calorimetry, synchrotron X-ray diffraction, dielectric
spectroscopy, and electro-optical tests.
PMID- 28413751
TI - Step-by-Step Design and Synthesis of Au@SiO2@Phenyl-azathiacrown for SERS-Based
Specific Quantification of Inorganic Mercury.
AB - Direct SERS-based quantification of inorganic metal species has been a problem,
because they have a small Raman cross-section or even no vibrational mode. Here,
we report a new strategy for SERS-based quantification of such metal species, as
exemplified by inorganic mercury (HgII) in waters. Step-by-step design and
synthesis from azathioethers [3, 9-dithia-6-monoazaundecane (DMA) and 3,6,12,15
tetrathia-9-monoazaheptadecane (TTM)] to an azathiacrown [7-aza-1,4,10,13
tetrathiacyclohexadecane (NS4)] demonstrate an improved S-pulling effect and size
fit specificity towards HgII to form Hg-S bonds. Modification of NS4 on the
surface of Au@SiO2 by using a 4-(bromomethyl)benzoic linker enabled direct SERS
based specific quantification of HgII for the first time, in which the ultrathin
layer (ca. 2 nm) that covered the Au core (55 nm) could be a barrier preventing
the Au core from having direct interaction with the HgII, and with phenyl serving
as an internal standard (IS). The ratio of the Hg-S SERS band intensity at 270 cm
1 to that of IS [(gammaCC+gammaCCC) at 1046 cm-1] was practically proportional to
the concentration of HgII, eliminating the inevitable uncertainties encountered
in SERS-based measurements. Such a methodology is expected to pave a new way for
SERS-based quantification of inorganic metal species when specific complexing
substrates and suitable ISs are designed.
PMID- 28413752
TI - Tetrahydropyranyl: A Non-aromatic, Mild-Acid-Labile Group for Hydroxyl Protection
in Solid-Phase Peptide Synthesis.
AB - The use of the tetrahydropyranyl (Thp) group for the protection of serine and
threonine side-chain hydroxyl groups in solid-phase peptide synthesis has not
been widely investigated. Ser/Thr side-chain hydroxyl protection with this acid
labile and non-aromatic moiety is presented here. Although Thp reacts with free
carboxylic acids, it can be concluded that to introduce Thp ethers at the
hydroxyl groups of N-protected Ser and Thr, protection of the C-terminal carboxyl
group is unnecessary due to the lability of Thp esters. Thp-protected Ser/Thr
containing tripeptides are synthesized and the removal of Thp studied in low
concentrations of trifluoroacetic acid in the presence of cation scavengers.
Given its general stability to most non-acidic reagents, improved solubility of
its conjugates and ease with which it can be removed, Thp emerges as an effective
protecting group for the hydroxyl groups of Ser and Thr in solid-phase peptide
synthesis.
PMID- 28413754
TI - An Approach Toward Replacing Vanadium: A Single Organic Molecule for the Anode
and Cathode of an Aqueous Redox-Flow Battery.
AB - By combining a viologen unit and a 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)
radical in one single combi-molecule, an artificial bipolar redox-active
material, 1-(4-(((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)carbonyl)benzyl)
1'-methyl-[4,4'-bipyridine]-1,1'-diium-chloride (VIOTEMP), was created that can
serve as both the anode (-0.49 V) and cathode (0.67 V vs. Ag/AgCl) in a water
based redox-flow battery. While it mimics the redox states of flow battery metals
like vanadium, the novel aqueous electrolyte does not require strongly acidic
media and is best operated at pH 4. The electrochemical properties of VIOTEMP
were investigated by using cyclic voltammetry, rotating disc electrode
experiments, and spectroelectrochemical methods. A redox-flow battery was built
and the suitability of the material for both electrodes was demonstrated through
a polarity-inversion experiment. Thus, an organic aqueous electrolyte system
being safe in case of cross contamination is presented.
PMID- 28413753
TI - Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a
Polysilane/SiO2-Supported Palladium Catalyst under Continuous-Flow Conditions.
AB - Hydrogenation of nitriles to primary amines with heterogeneous catalysts under
liquid-phase continuous-flow conditions is described. Newly developed
polysilane/SiO2-supported Pd was found to be an effective catalyst and various
nitriles were converted into primary amine salts in almost quantitative yields
under mild reaction conditions. Interestingly, a complex mixture was obtained
under batch conditions. Lifetime experiments showed that this catalyst remained
active for more than 300 h (TON>=10 000) without loss of selectivity and no metal
leaching from the catalyst occurred. By using this continuous-flow hydrogenation,
synthesis of venlafaxine, an antidepressant drug, has been accomplished.
PMID- 28413755
TI - One-Pot Synthesis of a bis-Pocket Corrole through a 14-fold Bromination Reaction.
AB - A one-pot protocol, effecting 14-fold bromination with elemental bromine, has
afforded copper beta-octabromo-meso-tris(2,6-dibromo-3,5-dimethoxyphenyl)corrole,
a new bis-pocket metallocorrole. The Cu complex underwent smooth demetalation
under reductive conditions, affording the free corrole ligand, which in turn
could be readily complexed to MnIII and AuIII. A single-crystal X-ray structure
was obtained for the MnIII complex.
PMID- 28413756
TI - Trifluoroethoxy-Coated Subphthalocyanine affects Trifluoromethylation of Alkenes
and Alkynes even under Low-Energy Red-Light Irradiation.
AB - Photoredox chemical reactions induced by visible light have undergone a
renaissance in recent years. Polypyridyl dyes such as Ir(ppy)3 and Ru(bpy)3 are
key catalysts in this event, and blue- or white-light irradiation is required for
the chemical transformations. However, it remains a challenge to achieve
reactions under the lower energy of red light. We disclose, herein, that
trifluoroethoxy-coated subphthalocyanine realizes the red-light-driven
trifluoromethylation of alkenes and alkynes with trifluoromethyl iodide in good
to-high yields. Perfluoroalkylations were also achieved under red light. The
reaction mechanism is discussed with the support of UV/Vis spectroscopy and
cyclic voltammetry of trifluoroethoxy-coated subphthalocyanine. Light
irradiation/dark study also supports the proposed mechanism.
PMID- 28413758
TI - De Novo Modular Development of a Foldameric Protein-Protein Interaction Inhibitor
for Separate Hot Spots: A Dynamic Covalent Assembly Approach.
AB - Protein-protein interactions stabilized by multiple separate hot spots are highly
challenging targets for synthetic scaffolds. Surface-mimetic foldamers bearing
multiple recognition segments are promising candidate inhibitors. In this work, a
modular bottom-up approach is implemented by identifying short foldameric
recognition segments that interact with the independent hot spots, and connecting
them through dynamic covalent library (DCL) optimization. The independent hot
spots of a model target (calmodulin) are mapped with hexameric beta-peptide
helices using a pull-down assay. Recognition segment hits are subjected to a
target-templated DCL ligation through thiol-disulfide exchange. The most potent
derivative displays low nanomolar affinity towards calmodulin and effectively
inhibits the calmodulin-TRPV1 interaction. The DCL assembly of the folded
segments offers an efficient approach towards the de novo development of a high
affinity inhibitor of protein-protein interactions.
PMID- 28413759
TI - Acid-Responsive N-Heteroacene-Based Material Showing Multi-Emission Colors.
AB - An acid-responsive N-heteroacene-based material has been prepared, which shows a
blue emission color in a film. The protonation of this material in a thin film
gives rise to remarkable changes in luminescent color compared to that in
solution states. As the protonation of N-heteroacene molecules in films gradually
occurs, their emission color can be tuned by adjusting the exposure time of the
thin films to HCl vapor.
PMID- 28413757
TI - Versatile Two-Step Functionalization of Nanocarbons: Grafting of Propargylic
Groups and Click Post-Functionalization.
AB - Chemical functionalization of nanocarbons is essential for further applications
in various fields. We developed a facile, inexpensive, and gram-scale one-pot
route towards alkynyl-functionalized nanocarbons. Nucleophilic
addition/propargylic capture places alkyne moieties at the surface of carbon
nanotubes (CNTs) and graphene. Thermogravimetric analysis coupled with mass
spectrometry and Raman analysis confirmed the efficiency of this process.
Conductivity measurements demonstrated the maintenance of the CNT electrical
properties. The attached alkynyl moieties were reacted with various azide
derivatives through the click-Huisgen [3+2] cycloaddition and characterized with
XPS. The efficient addition of those derivatives enables the application of our
finding in various fields. This route is a reliable and convenient alternative to
the known diazonium functionalization and oxidation-esterification reactions to
graft alkyne groups.
PMID- 28413760
TI - Synthesis of C2-Symmetric Diphosphormonoamidites and Their Use as Ligands in Rh
Catalyzed Hydroformylation: Relationships between Activity and Hydrolysis
Stability.
AB - A series of diphosphoramidites has been synthetized with a piperazine,
homopiperazine, and an acyclic 1,2-diamine unit in the backbone. New compounds
were tested alongside related N-acyl phosphoramidites as ligands in the Rh
catalyzed hydroformylation of n-octenes to investigate their influence on the
activity and regioselectivity. A subsequent study of their hydrolysis stability
revealed that the most stable ligands induced the highest activity in the
catalytic reaction.
PMID- 28413761
TI - Synthesis, Characterization, and Antimicrobial Activity of Near-IR Photoactive
Functionalized Gold Multibranched Nanoparticles.
AB - Surface-modified gold multibranched nanoparticles (AuMs) were prepared by simple
chemical reduction of gold chloride aqueous solution followed by in situ
modification by using water-soluble arenediazonium tosylates with different
functional organic groups. Chemical and morphological structures of the prepared
nanoparticles were examined by using transmission electron and scanning electron
microscopies. The covalent grafting of organic compounds was confirmed by
scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX)
and Raman spectroscopy techniques. Covalent functionalization of nanoparticles
significantly expands the range of their potential uses under physiological
conditions, compared with traditional non-covalent or thiol-based approaches. The
antibacterial effect of the surface-modified AuMs was evaluated by using
Escherichia coli and Staphylococcus epidermidis bacteria under IR light
illumination and without external triggering. Strong plasmon resonance on the
AuMs cups leads to significant reduction of the light power needed kill bacteria
under the mild conditions of continuous illumination. The effect of the surface
modified AuMs on the light-induced antibacterial activities was founded to be
dependent on the grafted organic functional groups.
PMID- 28413762
TI - Photothermal Conversion of W18O49 with a Tunable Oxidation State.
AB - W18O49 with a tunable oxidation state was prepared by addition of NaNO3 or NaBH4
as a redox agent in the solvothermal system. The addition of redox agents has no
influence on the crystallization of W18O49. The obtained W18O49 structures keep
their morphology as a bundle of nanowires with a regular hexagonal on the cross
section. W18O49 exhibits strong valence-dependent absorption features in the near
IR region. Reduced W18O49 with more W5+ has a higher concentration of oxygen
vacancies, which enhances the localized surface plasmon resonance effect. Reduced
W18O49 exhibits a high photothermal conversion efficiency of 59.6 % and has good
photothermal stability.
PMID- 28413763
TI - Relationship between Side-Chain Polarity and the Self-Assembly Characteristics of
Perylene Diimide Derivatives in Aqueous Solution.
AB - Perylene-3,4,9,10-tetracarboxylic acid diimides (PDIs) have recently gained
considerable interest for water-based biosensing applications. PDIs have been
studied intensively in the bulk state, but their physical properties in aqueous
solution in interplay with side-chain polarity are, however, poorly understood.
Therefore, three perylene diimide based derivatives were synthesized to study the
relationship between side-chain polarity and their self-assembly characteristics
in water. The polarity of the side chains was found to dictate the size and
morphology of the formed aggregates. Side-chain polarity rendered the self
assembly and photophysical properties of the PDIs-both important for imminent
water-based applications-and these were revealed to be especially responsive to
changes in solvent composition.
PMID- 28413764
TI - Engineering Functions into Platinum and Platinum-Rhodium Nanoparticles in a One
Step Microwave Irradiation Synthesis.
AB - Platinum (Pt) and platinum-rhodium (PtRh) nanoparticles (NPs) are active
catalysts for a range of important industrial reactions, and their response has
been shown to be affected by size, morphology, composition, and architectural
configuration. We report herein the engineering of these functionalities into NPs
by suitably modifying our single-step fabrication process by using microwave
irradiation dielectric heating. NPs with different morphologies are acquired by
manipulating the reaction kinetics with the concentration of the capping agent
while keeping the reaction time constant. Pt@Rh core@shell octopod-cube, Pt
truncated-cube, and cube and small-sphere NPs having "near-monodisperse"
distributions and average sizes in the range of 4 to 18 nm are obtained. By
increasing the microwave time the composition of Pt@Rh can be tuned, and NPs with
a Rh-rich shell and a tunable Pt100-x Rh x (x<=41 at %) core are fabricated.
Finally, alloy bimetallic PtRh NPs with controlled composition are designed by
simultaneous tuning of the relative molar ratio of the metal precursors and the
microwave irradiation time.
PMID- 28413765
TI - Experimental and Theoretical Examination of the Radical Cations Obtained from the
Chemical and Electrochemical Oxidation of 5-Aminothiazoles.
AB - Chemical or electrochemical one-electron oxidation of 5-N-arylaminothiazoles was
found to afford stable radical cations. For chemical oxidation, 1 equivalent of
[(4-BrC6H4)3N][SbCl6] (Magic Blue, MB) was added to CH2Cl2 solutions of the
thiazoles, and the thus-obtained radicals showed light absorption in the near
infrared region. Electrochemical oxidation also led to bathochromic shifts in the
absorption bands, and the obtained spectra were similar to those derived from the
chemically oxidized species. These radicals afforded electron paramagnetic
resonance (EPR) spectra that are consistent with the notion of stable nitrogen
radicals (half-life<=385 h). The EPR spectrum of a thiazole containing 4
dimethylaminophenyl groups on the nitrogen atom at the 5-position changed
significantly upon adding >3 equivalents of MB. Details of the electronic
structures of the experimentally obtained radical cations were generated from
theoretical calculations.
PMID- 28413766
TI - Five-Component Self-Assembly of Cucurbituril-Based Hetero-pseudorotaxanes.
AB - [5]Pseudorotaxanes can be obtained by self-sorting using heteroditopic guests and
various cucurbituril homologues as hosts. The assembly and chemically induced
disassembly of the pseudorotaxanes can be monitored by measuring the fluorescence
of the anthracene guest in solution. Mass spectral evidence for the
supramolecular assemblies is obtained in the gas phase. The disassembly in the
gas phase can be achieved by collision-induced dissociation leading to the
corresponding [2]- and [3]pseudorotaxanes.
PMID- 28413767
TI - Unique Image Characteristics of an Occipital Primary Chondroblastic Osteosarcoma:
A Rare Case Report and a Brief Literature Review.
AB - Primary osteosarcomas of the skull and skull base are rare and comprise < 2% of
all skull tumors. In head and neck osteosarcomas, the chondroblastic subtype
occurs most frequently, which has an exceedingly poor outcome, but its image
characteristic remains unknown. Herein, we report a case in the right occipital
bone of the skull base and the unique characteristics of image. Pathologic
examination of the surgical specimens led to the diagnosis of chondroblastic
osteosarcomas. We believe those image characteristics can improve the
understanding of skull chondroblastic osteosarcoma and the preoperative
diagnosis.
PMID- 28413768
TI - Surgical Resection of an Optic Nerve Sheath Meningioma: Relevance of Endoscopic
Endonasal Approaches to the Optic Canal.
AB - Optic nerve sheath meningiomas (ONSMs) account for less than 2% of meningiomas
and 1.7% of orbital tumors. Although rare, the management of these tumors is
important as unilateral blindness often results in untreated cases. Radiotherapy
has emerged as the preferred treatment. However, therapies for ONSMs are
controversial due to the variable natural history of the disease and limitations
of surgical and radiotherapy options. A 60-year-old woman presented with
monocular left diminished color perception and blurred vision. Magnetic resonance
imaging demonstrated a homogenously enhancing 5-mm left optic nerve mass with
evidence of nerve compression. Conservative management was advised. However, 1
month after diagnosis her visual acuity deteriorated further. Because of the
small focal location of the tumor within the optic canal, surgery was considered.
Given the tumor's location inferomedial to the optic nerve, an endoscopic
endonasal approach to the optic canal was performed. This patient recovered fully
with resolution of visual symptoms immediately following surgery. Postoperative
imaging 24 hours after surgery demonstrated gross total resection of the tumor; 1
year postoperatively the patient has a normal ophthalmologic examination. This
report highlights the value of endoscopic endonasal approaches in the management
of select optic canal pathology, otherwise inaccessible via transcranial
approaches.
PMID- 28413769
TI - Update on Biomarkers to Monitor Clinical Efficacy Response During and Post
Treatment in Allergen Immunotherapy.
AB - Allergen immunotherapy (AIT) is an immune modulating treatment for allergic
diseases. Although highly effective, some patients do not respond to the
treatment. To date there are no surrogate biomarkers that are predictive of the
clinical response to AIT. More and more is known about the underlying
immunological mechanism involved in AIT. Through modulation of both innate and
adaptive immune responses, involving reduced ILC2 and enhanced Treg and Breg
induction and functionality, along with induction of IgG4 antibody production
which have the capacity to inhibit both allergen-induced basophil responsiveness
and CD23-mediated IgE-facilitated allergen presentation, the result is an immune
skewing towards a more balanced Type I response. So far, however there is not a
clear correlation with the observed immunological changes and predictive
correlates of clinical efficacy. The most promising biomarker of successful AIT
is IgE-FAB as a reflection of functional IgG4. Cellular responses and cytokine
analysis gives a great deal of insight into the mechanisms of AIT but may not
represent useful or indeed reliable biomarkers in a clinical setting. There is a
need for more research for confirmation and interpretation of the possible
association with biomarkers and clinical response to AIT.
PMID- 28413770
TI - Biophysical regulation of cell reprogramming.
AB - Induced pluripotent stem (iPS) cell reprogramming and direct reprogramming are
promising approaches for disease modeling and personalized medicine. However,
these processes are yet to be optimized. Biomaterials are increasingly integrated
into cell reprogramming strategies in order to engineer the microenvironment,
improve reprogramming efficiency and achieve effective in situ cell
reprogramming. Although there are some studies on the role of biomaterials in iPS
cell reprogramming, their effect on direct cell conversion has not been fully
explored. Here we review the recent advances in the use of biomaterials for iPS
cell reprogramming and direct reprogramming, with a focus on the biophysical
aspect. We further highlight the future challenges and directions of the field.
PMID- 28413772
TI - Postoperative complications with cryotherapy in bone tumors.
AB - The technique of cryosurgery has been used to control local recurrence in a
variety of benign and malignant bone tumors. Early studies revealed significant
complication rates (25%) that included fracture, infection, and soft tissue
injury. Our method of cryosurgery has yielded excellent tumor control with
improved complication rates. The objective of this study is to determine the
characteristics of postoperative complications after pouring liquid nitrogen into
curettaged bone defects, and to review our current indications and surgical
technique in bone tumor management. We reviewed charts in over 200 patients who
received cryoablation for bone tumors from 1994 to 2015. Imaging studies were
evaluated in all patients diagnosed with a complication. All patients receiving
cryotherapy had soft tissue management intraoperatively that included warm saline
directed to the structures. Liquid nitrogen was poured into the bone defect and
in some cases, additional spraying with a cryogun into the defect was performed.
The majority of cryotherapy was used in cases of active or aggressive benign
tumors. Our low complication rate of 2.34% included 1 post-operative fracture, 3
infection, and 1 paraesthesia. Bone graft or cementation was used in the majority
of patients, all of which fully incorporated. Cryoablation is an excellent from
of adjuvant therapy for active and aggressive benign tumors and may be used in
malignant tumors as well. Soft tissue protection is critical to avoid skin
necrosis and wound breakdown. We recommend the use of cryotherapy in active and
aggressive bone tumors as an adjuvant treatment prior to bone grafting or
cementation.
PMID- 28413773
TI - A M. avium complex spondylodiscitis in a middle-aged woman with diabetes.
AB - Spondylodiscitis, the inflammation of the vertebral bodies and the intervertebral
disk space, is the reason for low back pain in a minority of cases. This is
caused by various pathogens. Mycobacterium tuberculosis is responsible for 17-39%
of all the cases of spondylodiscitis. On the contrast, spondylodiscitis from non
tuberculous mycobacteria is extremely rare in literature. We describe a 68 -year
old diabetic woman which is the first case of bone marrow involvement by M.
intracellulare (member of M avium complex)with spondylodiscitis.
PMID- 28413771
TI - Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal
women with hormone sensitive breast cancer: Joint position statement of the IOF,
CABS, ECTS, IEG, ESCEO IMS, and SIOG.
AB - BACKGROUND: Several guidelines have been reported for bone-directed treatment in
women with early breast cancer (EBC) for averting fractures, particularly during
aromatase inhibitor (AI) therapy. Recently, a number of studies on additional
fracture related risk factors, new treatment options as well as real world
studies demonstrating a much higher fracture rate than suggested by randomized
clinical controlled trials (RCTs). Therefore, this updated algorithm was
developed to better assess fracture risk and direct treatment as a position
statement of several interdisciplinary cancer and bone societies involved in the
management of AI-associated bone loss (AIBL). PATIENTS AND METHODS: A systematic
literature review identified recent advances in the management of AIBL. Results
with individual agents were assessed based on trial design, size, follow-up, and
safety. RESULTS: Several fracture related risk factors in patients with EBC were
identified. Although, the FRAX algorithm includes fracture risk factors (RF) in
addition to BMD, it does not seem to adequately address the effects of AIBL.
Several antiresorptive agents can prevent and treat AIBL. However, concerns
regarding compliance and long-term safety remain. Overall, the evidence for
fracture prevention is strongest for denosumab 60 mg s.c. every 6 months.
Additionally, recent studies as well as an individual patient data meta-analysis
of all available randomized trial data support additional anticancer benefits
from adjuvant bisphosphonate treatment in postmenopausal women with a 34%
relative risk reduction in bone metastasis and 17% relative risk decrease in
breast cancer mortality that needs to be taken into account when advising on
management of AIBL. CONCLUSIONS: In all patients initiating AI treatment,
fracture risk should be assessed and recommendation with regard to exercise and
calcium/vitamin D supplementation given. Bone-directed therapy should be given to
all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one
additional RF, or with >=2 risk factors (without BMD) for the duration of AI
treatment. Patients with T-score>-1.5 SD and no risk factors should be managed
based on BMD loss during the first year and the local guidelines for
postmenopausal osteoporosis. Compliance should be regularly assessed as well as
BMD on treatment after 12 - 24 months. Furthermore, because of the decreased
incidence of bone recurrence and breast cancer specific mortality, adjuvant
bisphosphonates are recommended for all postmenopausal women at significant risk
of disease recurrence.
PMID- 28413774
TI - A diffuse lung emphysema, severe pulmonary hypertension and lack of airflow
limitation.
AB - Pulmonary veno-occlusive disease is characterized by remodeling of pulmonary
arteries, capillaries and venules. We report a case of diffuse lung emphysema and
pulmonary veno-occlusive disease with the characteristic of having no airflow
limitation. A very low diffusing capacity for carbon monoxide and results of high
resolution computed tomography of the chest suggested pulmonary veno-occlusive
disease. The diagnosis was confirmed on histological analysis after lung
transplantation. The combination of results of the computed tomography of the
chest and the histological analysis suggested a relationship between diffuse lung
emphysema and remodeling of pulmonary vessels. A distinctive pattern of mild-to
moderate airflow limitation in patients with chronic obstructive pulmonary
disease and severe pulmonary hypertension has been described. This observation of
the combination of diffuse emphysema, pulmonary veno-occlusive disease and no
airflow limitation supports further pathophysiological studies on severe
pulmonary hypertension in chronic obstructive pulmonary disease.
PMID- 28413775
TI - An interesting case of mycoplasma pneumonia associated multisystem involvement
and diffuse alveolar hemorrhage.
AB - Severe mycoplasma pneumonia is a rare entity with only 0.5-2% of cases having a
fulminant course. We present a 74-year-old woman with hypertension, diabetes
mellitus and remote history of marginal zone B-cell lymphoma admitted with
abdominal pain and diarrhea of 1-2 days associated with body-aches, dyspnea, dry
cough and weight loss for 2-3 weeks. On physical exam, she was febrile,
tachypneic, tachycardic and hypoxic on room air. Chest examination revealed
diffuse crackles and end-expiratory wheezes. Laboratory tests showed anemia,
acute-on-chronic kidney injury and hyaline casts and epithelial cells in the
urine analysis. Chest roentgenogram and computed tomograhphy scan showed
pulmonary infiltrates. Intravenous ceftriaxone and azithromycin with
bronchodilators were initiated. Her clinical course was complicated by hypoxic
respiratory failure, hemoptysis, and worsening of infiltrates, requiring
intubation and mechanical ventilation. Bronchoscopic bronchoalveolar lavage was
consistent with diffuse alveolar hemorrhage (DAH). The patient's serum was
positive for IgM antibody to Mycoplasma pneumoniae [1134 U/mL] and Anti-I
specific IgM-cold-agglutining [1:40]. A diagnosis of severe mycoplasma infection
with DAH was made. The patient was treated with an additional course of
doxycycline, pulse dose steroids and plasmapharesis with good clinical response.
Surgical lung biopsy showed focal acute lung injury. Bone marrow biopsy and fat
pad biopsy were normal. She was liberated from mechanical ventilation and
discharged. She returned within 24 hours of discharge with cardiac arrest and new
onset right-bundle-branch-block. We hypothesize our patient had severe mycoplasma
pneumonia with DAH and multisystem complications of the same including a possible
venous thrombo-embolic episode leading to her demise.
PMID- 28413776
TI - Dissociable neural processes during risky decision-making in individuals with
Internet-gaming disorder.
AB - Risk-taking is purported to be central to addictive behaviors. However, for
Internet gaming disorder (IGD), a condition conceptualized as a behavioral
addiction, the neural processes underlying impaired decision-making (risk
evaluation and outcome processing) related to gains and losses have not been
systematically investigated. Forty-one males with IGD and 27 healthy comparison
(HC) male participants were recruited, and the cups task was used to identify
neural processes associated with gain- and loss-related risk- and outcome
processing in IGD. During risk evaluation, the IGD group, compared to the HC
participants, showed weaker modulation for experienced risk within the bilateral
dorsolateral prefrontal cortex (DLPFC) (t = - 4.07; t = - 3.94; PFWE < 0.05) and
inferior parietal lobule (IPL) (t = - 4.08; t = - 4.08; PFWE < 0.05) for
potential losses. The modulation of the left DLPFC and bilateral IPL activation
were negatively related to addiction severity within the IGD group (r = - 0.55; r
= - 0.61; r = - 0.51; PFWE < 0.05). During outcome processing, the IGD group
presented greater responses for the experienced reward within the ventral
striatum, ventromedial prefrontal cortex, and orbitofrontal cortex (OFC) (t =
5.04, PFWE < 0.05) for potential gains, as compared to HC participants. Within
the IGD group, the increased reward-related activity in the right OFC was
positively associated with severity of IGD (r = 0.51, PFWE < 0.05). These
results provide a neurobiological foundation for decision-making deficits in
individuals with IGD and suggest an imbalance between hypersensitivity for reward
and weaker risk experience and self-control for loss. The findings suggest a
biological mechanism for why individuals with IGD may persist in game-seeking
behavior despite negative consequences, and treatment development strategies may
focus on targeting these neural pathways in this population.
PMID- 28413779
TI - Pufferfish nests vs. parasite hooks: A bizarre resemblance.
AB - Image 1.
PMID- 28413780
TI - Generalized epilepsy in Baraitser-Winter cerebrofrontofacial syndrome.
AB - *Baraitser-Winter cerebrofrontofacial syndrome (BWMS) is caused by actin gene
mutations.*Key features of BWMS are ptosis, hypertelorism, iris colobomata, and
mental retardation.*Generalized epilepsy is seen in half of those with
BWMS.*Seizures in BWMS can be absence, myoclonic, tonic, or tonic-clonic.
PMID- 28413778
TI - Family history and APOE4 risk for Alzheimer's disease impact the neural
correlates of episodic memory by early midlife.
AB - Episodic memory impairment is a consistent, pronounced deficit in pre-clinical
stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for
AD exhibit altered brain function several decades prior to the onset of AD
related symptoms. In the current event-related fMRI study of spatial context
memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a
family history of late onset AD (MA+ FH), or a combined + FH and apolipoprotein E
epsilon4 allele risk factors for AD (MA+ FH + APOE4), will exhibit differences in
encoding and retrieval-related brain activity, compared to - FH - APOE4 MA
controls. We also hypothesized that the two at-risk MA groups will exhibit
distinct patterns of correlation between brain activity and memory performance,
compared to controls. To test these hypotheses we conducted multivariate task,
and behavior, partial least squares analysis of fMRI data obtained during
successful context encoding and retrieval. Our results indicate that even though
there were no significant group differences in context memory performance, there
were significant differences in brain activity and brain-behavior correlations
involving the hippocampus, inferior parietal cortex, cingulate, and precuneus
cortex in MA with AD risk factors, compared to controls. In addition, we observed
that brain activity and brain-behavior correlations in anterior-medial PFC and in
ventral visual cortex differentiated the two MA risk groups from each other, and
from MAcontrols. Our results indicate that functional differences in episodic
memory-related regions are present by early midlife in adults with + FH and +
APOE-4 risk factors for late onset AD, compared to middle-aged controls.
PMID- 28413781
TI - Sequencing and de novo transcriptome assembly of the Chinese giant salamander
(Andrias davidianus).
AB - Next-generation technologies for determination of genomics and transcriptomics
composition have a wide range of applications. Andrias davidianus, has become an
endangered amphibian species of salamander endemic in China. However, there is a
lack of the molecular information. In this study, we obtained the RNA-Seq data
from a pool of A. davidianus tissue including spleen, liver, muscle, kidney,
skin, testis, gut and heart using Illumina HiSeq 2500 platform. A total of
15,398,997,600 bp were obtained, corresponding to 102,659,984 raw reads. A total
of 102,659,984 reads were filtered after removing low-quality reads and trimming
the adapter sequences. The Trinity program was used to de novo assemble 132,912
unigenes with an average length of 690 bp and N50 of 1263 bp. Unigenes were
annotated through number of databases. These transcriptomic data of A. davidianus
should open the door to molecular evolution studies based on the entire
transcriptome or targeted genes of interest to sequence. The raw data in this
study can be available in NCBI SRA database with accession number of SRP099564.
PMID- 28413777
TI - Sex differences in the interacting roles of impulsivity and positive alcohol
expectancy in problem drinking: A structural brain imaging study.
AB - Alcohol expectancy and impulsivity are implicated in alcohol misuse. However, how
these two risk factors interact to determine problem drinking and whether men and
women differ in these risk processes remain unclear. In 158 social drinkers (86
women) assessed for Alcohol Use Disorder Identification Test (AUDIT), positive
alcohol expectancy, and Barratt impulsivity, we examined sex differences in these
risk processes. Further, with structural brain imaging, we examined the neural
bases underlying the relationship between these risk factors and problem
drinking. The results of general linear modeling showed that alcohol expectancy
best predicted problem drinking in women, whereas in men as well as in the
combined group alcohol expectancy and impulsivity interacted to best predict
problem drinking. Alcohol expectancy was associated with decreased gray matter
volume (GMV) of the right posterior insula in women and the interaction of
alcohol expectancy and impulsivity was associated with decreased GMV of the left
thalamus in women and men combined and in men alone, albeit less significantly.
These risk factors mediated the correlation between GMV and problem drinking.
Conversely, models where GMV resulted from problem drinking were not supported.
These new findings reveal distinct psychological factors that dispose men and
women to problem drinking. Although mediation analyses did not determine a causal
link, GMV reduction in the insula and thalamus may represent neural phenotype of
these risk processes rather than the consequence of alcohol consumption in non
dependent social drinkers. The results add to the alcohol imaging literature
which has largely focused on dependent individuals and help elucidate alterations
in brain structures that may contribute to the transition from social to habitual
drinking.
PMID- 28413782
TI - APMicroDB: A microsatellite database of Acyrthosiphon pisum.
AB - Pea aphids represent a complex genetic system that could be used for QTL
analysis, genetic diversity and population genetics studies. Here, we described
the development of first microsatellite repeat database of the pea aphid
(APMicroDB), accessible at "http://deepaklab.com/aphidmicrodb". We identified
3,40,233 SSRs using MIcroSAtellite (MISA) tool that was distributed in 14,067
(out of 23,924) scaffold of the pea aphid. We observed 89.53% simple repeats of
which 73.41% were mono-nucleotide, followed by di-nucleotide repeats. This
database stored information about the repeats kind, GC content, motif type (mono
hexa), genomic location etc. We have also incorporated the primer information
derived from Primer3 software of the 2504 bp flanking region of the identified
marker. Blast tool is also provided for searching the user query sequence for
identified marker and their primers. This work has an immense use for scientific
community working in the field of agricultural pest management, QTL mapping, and
host-pathogen interaction analysis.
PMID- 28413784
TI - Correction.
AB - [This corrects the article DOI: 10.7860/JCDR/2015/11926.6278.].
PMID- 28413783
TI - Two single nucleotide polymorphisms sites in alpha1-AT gene and their association
with somatic cell score in Chinese Holstein cows.
AB - BACKGROUND: Alpha 1-antitrypsin (alpha1-AT) may affect the susceptibility of
mastitis in dairy cattle for its possible role in the protection of lactoferrin
from proteolytic degradation in the mammary. Milk somatic cell score (SCS) is a
logarithmic transformation of the milk somatic cell count widely used as an index
to evaluate mastitis. To study the relationships of alpha1-AT gene and SCS in
Chinese Holstein cows, methods of PCR-SSCP, DNA sequencing, PCR-RFLP, and CRS-PCR
technologies were used to detect single nucleotide polymorphisms sites in alpha1
AT gene. RESULTS: Two polymorphic sites at G5503A and G5746C of alpha1-AT gene
were found. AA (0.3633), AB (0.4644) and BB (0.1723) genotypes were detected at
G5503A site, CC (0.3483), CD (0.4906) and DD (0.1611) genotypes were found at
G5746C in Chinese Holstein cows. Least squares mean of SCS for individuals with
BB genotype was significantly lower than that with AA and AB genotype (p < 0.01),
and that with AB genotype was significantly lower than that with AA (p < 0.05).
There was no significant difference among individuals with CC, CD and DD
genotypes (p > 0.05). Least squares mean of SCS for individuals with BBDD
genotype combination were significantly lower than those with AACC and AACD (p <
0.05). CONCLUSIONS: Statistical analysis indicated that B allele and BBDD
genotype combination of alpha1-AT can improve mastitis resistance in dairy
cattle.
PMID- 28413785
TI - Efficacy of erlotinib as first-line maintenance therapy in patients with locally
advanced or metastatic nonsmall cell lung cancer who have not experienced disease
progression or unacceptable toxicity during chemotherapy.
AB - BACKGROUND: First-line maintenance with erlotinib in nonsmall cell lung cancer
(NSCLC) patients without progression after four cycles of chemotherapy was well
tolerated and significantly prolonged progression-free survival (PFS) compared
with placebo. AIM AND DESIGN: This open-label, single arm, Phase IV,
interventional study was designed to evaluate erlotinib as first-line maintenance
after chemotherapy in Indian NSCLC patients. Primary efficacy objective was to
evaluate PFS rate (PFSR) at week 52 and secondary objectives were determination
of PFS, overall survival (OS), overall response rate (ORR), disease control rate,
and safety. SUBJECTS AND METHODS: Patients were treated with erlotinib until
disease progression/death/unacceptable toxicity or end of study. Patients with
disease progression underwent scheduled clinical assessments every 12 weeks
thereafter. Kaplan-Meier estimates were used to evaluate PFSR, PFS, and OS. The
ORR was summarized using number and percentage along with two-sided 95% Clopper
Pearson confidence interval. The incidence of adverse events (AEs) and serious
AEs (SAEs) was tabulated according to severity, outcome, and relationship to
erlotinib. RESULTS: Of the 51 enrolled patients, 47 patients completed the study
(2: Continuing treatment, 41: Disease progression, and 4: Death) and four
patients discontinued treatment (3: Lost to follow-up; 1: Withdrew consent). PFSR
was 22.5% at 12 months, median PFS 99 days (14.14 weeks), and median OS was 671
days (22 months). The probability of OS was 74.5% at 14 months. The ORR was
25.5%, and disease control rate was 55.3%. AEs were reported in 62.7% and SAE in
7.8% of patients. Common AEs were diarrhea and rash. CONCLUSIONS: Erlotinib was
well tolerated by Indian patients in first-line maintenance setting and resulted
in median PFS of 14 weeks and median OS of 22 months better than previously
reported and with no new safety concerns in this population.
PMID- 28413786
TI - Surgical management of bronchopulmonary carcinoids: A single center experience.
AB - INTRODUCTION: Bronchopulmonary carcinoids are uncommon tumors with relatively
indolent biological behavior but a distinct malignant potential. Surgery is the
mainstay of treatment. Our aim was to study preoperative characteristics,
surgical approaches, and outcome in patients with bronchopulmonary carcinoid
tumors. PATIENTS AND METHODS: This retrospective study was done in the Department
of Surgical Oncology of a Tertiary Teaching Hospital of North India. The case
records of all the patients who underwent surgical treatment for lung neoplasms
and were diagnosed to have bronchopulmonary carcinoids were reviewed. Details
concerning the clinical presentation, preoperative therapy, operative procedure,
postoperative complications, and outcome were retrieved from the case records.
RESULTS: Sixteen patients who underwent surgical treatment were found to have
bronchopulmonary carcinoids on histopathological examination. The median age of
the patients was 34 years (range 18-62 years). There were 11 men and five women.
All patients were symptomatic, and the median duration of symptoms was 12 months
(range 6-72 months) before presentation. Six patients had received antitubercular
treatment before presentation, and one patient had been treated with chemotherapy
due to misdiagnosis. Surgical procedures included six pneumonectomies (one with
carinoplasty), four bilobectomies, three lobectomies, and three bronchoplastic
procedures (two with lobectomy and one with bilobectomy). There was no
postoperative mortality; three patients had morbidity in the form of lobar
collapse, prolonged pleural collection, and surgical site infection. With a
median follow-up time of 11 months (range 2-85 months), all the 16 patients are
alive and disease-free. CONCLUSIONS: Delayed presentation and misdiagnosis of
bronchial carcinoid are major concerns in North India. Adequate surgical
resection can be performed without undue morbidity and is associated with good
long-term results.
PMID- 28413787
TI - Billiary obstruction in a metastatic tumor of the pancreas from breast cancer.
PMID- 28413788
TI - A tertiary care experience with paclitaxel and cetuximab as palliative
chemotherapy in platinum sensitive and nonsensitive in head and neck cancers.
AB - BACKGROUND: The combination of paclitaxel and cetuximab (PaCe) has led to an
encouraging response rate in Phase 2 setting with limited toxicity. The aim of
our study was to assess the efficacy of this regimen in our setting in platinum
sensitive and nonsensitive patients. METHODS: This was a retrospective analysis
of head and neck cancer patients treated with weekly PaCe as palliative
chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab
along with 80 mg/m2 of weekly paclitaxel was administered till either disease
progression or withdrawal of patient's consent. The toxicity and response were
noted in accordance with CTCAE version 4.02 and RECIST version 1.1 criteria,
respectively. The response rates between platinum sensitive and nonsensitive
patients were compared by Chi-square test. Overall survival (OS) and progression
free survival (PFS) were estimated by Kaplan-Meier survival method and log-rank
test was used for comparison. Cox proportional hazard model was used for
identification of factors affecting PFS and OS. RESULTS: One Hundred patients
with a median age of 52 years (interquartile range: 46-56 years) were included.
Forty-five patients (45%) were platinum insensitive, whereas 55 patients (55%)
were platinum sensitive. In platinum insensitive patients and sensitive patients,
the response rates were 38.5% and 22.2%, respectively (P = 0.104), whereas the
symptomatic benefit in pain was seen in 89.5% and 71.7%, respectively (P =
0.044). The median PFS in platinum insensitive and sensitive patients were 150
and 152 days, respectively (P = 0.932), whereas the median OS was 256 days (95%
confidence interval [95% CI]: 168.2-343.8 days) and 314 days (95% CI: 227.6-400.4
days), respectively (P = 0.23). Nineteen patients (19%) had grades 3-4 adverse
events during chemotherapy. CONCLUSION: Weekly paclitaxel combined with cetuximab
has promising efficacy and good tolerability in the palliative setting in
advanced head and neck cancer in both platinum sensitive and insensitive
patients.
PMID- 28413789
TI - Role of neoadjuvant chemotherapy in advanced carcinoma of the hypopharynx and
larynx.
AB - BACKGROUND: To assess the response rate and impact of neoadjuvant chemotherapy
(NACT) in advanced carcinoma of the hypopharynx and larynx. MATERIALS AND
METHODS: This is a retrospective case series of 80 patients with locally advanced
laryngopharynx carcinoma who received NACT from April 2010 to October 2011 at our
tertiary care center. The patients received NACT either for achieving
resectability or for organ preservation. RESULTS: Majority of the patients (60%)
had T4 a disease. Grade 3 and 4 neutropenia was seen in 18%, febrile neutropenia
in 4%, mucositis in 4%, diarrhea in 5%, and vomiting in 3% patients.
Resectability could be achieved in 34%, and larynx was preserved in 51% patients
at a mean follow-up of 13 months. CONCLUSIONS: NACT was safe with acceptable
toxicity. Majority of the patients who achieved resectability had oropharyngeal
involvement. NACT followed by concurrent chemoradiotherapy could provide a high
rate of organ preservation.
PMID- 28413790
TI - Long-term survival in a case of metastatic papillary renal cell carcinoma.
PMID- 28413791
TI - Safety and tolerability of Peg-grafeelTM, a pegfilgrastim, for the prophylactic
treatment of chemotherapy-induced neutropenia and febrile neutropenia: A
prospective, observational, postmarketing surveillance study in India.
AB - BACKGROUND: A granulocyte colony-stimulating factor, pegfilgrastim, is
efficacious though expensive for prophylactic treatment of chemotherapy-induced
neutropenia and febrile neutropenia. Biologics available and accessible today,
having acceptable safety-efficacy profiles, require postapproval studies for
better understanding of such drugs in clinical settings. AIM: This postmarketing
surveillance study evaluated the safety of prophylactic Peg-grafeelTM
(pegfilgrastim) in cancer patients with chemotherapy-induced neutropenia.
SETTINGS AND DESIGN: This prospective, noninterventional, single-arm, open-label
study was conducted at 10 study sites in India. METHODS: Patients received
subcutaneous 6 mg Peg-grafeelTM approximately 24 h following chemotherapy as part
of routine patient care. STATISTICAL ANALYSIS: Data were summarized
descriptively. RESULTS: The study included 250 patients (male: female =
36.4%:63.6%; median age, 54 [16-80] years). Most patients had Stage III (33.2%)
or IV (41.6%) cancers and received cyclophosphamide (37.2%) and doxorubicin
(31.6%) as chemotherapy. On an average, 4 Peg-grafeelTM doses were administered
per patient. Treatment-emergent adverse events (AEs) were reported in 115 (46%)
patients, the most common being vomiting (11.6%), pain (11.2%), nausea (8.4%),
and constipation (8.4%). Peg-grafeelTM-related AEs included pain (3.2%), asthenia
(2.4%), and arthralgia (1.2%). Bone pain (0.4%) and extremity pain (1.2%) were
rare. Grade 3/4 neutropenia and febrile neutropenia occurred in 4 (1.6%) and 3
(1.2%) patients, respectively. Serious AEs included vomiting (2.8%) and pyrexia
(2%). No new safety concerns were identified. None of the five deaths was
considered related to Peg-grafeelTM. CONCLUSION: The overall safety profile of
Peg-grafeelTM was consistent with the expected safety profile of pegfilgrastim in
patients with advanced malignancies in a clinical setting.
PMID- 28413792
TI - Epedimiologic, clinical profile and factors affecting the outcome in febrile
neutropenia.
AB - BACKGROUND: Febrile neutropenia (FN) is common in cancer patients particularly
hematologic malignancies due to intensive cytotoxic chemotherapy. It is an
important cause of morbidity, mortality and treatment delays. The risk is greater
in patients with ANC < 500/ mm3 and increases dramatically in those with ANC <
100/ mm3 and duration of neutropenia more than 1 week. AIMS AND OBJECTIVES: The
purpose of this study was to evaluate the incidence, demographic characteristics,
clinical profile, mortality, outcome and factors affecting the outcome in
patients with febrile neutropenia (FN) admitted at our Center between January
2011 and November 2012. MATERIALS AND METHODS: All cases of FN admitted in our
Institute between January 2011 and November 2012 were analyzed. Data was analyzed
using IBM statistic SPSS version 19. RESULTS: A total of 333 episodes of FN were
reviewed. Hematologic malignancies accounted for 299 (89.7%) episodes and 88% of
all the episodes had grade 4 neutropenia. There was a significant association
noted between high serum bilirubin, creatinine and outcome. Isolation of an
organism from blood culture, positive findings on chest X-ray and fungal
infection was associated with higher mortality. Association between transfusion
requirements and outcome was analyzed and it was observed that patients who had
multiple component transfusions vs single component ones were at a significantly
higher risk of death. There were only 7 deaths noted among the patient
population. CONCLUSION: Leukemias are the leading cause of FN at our Institute.
Higher bilirubin, creatinine, chest imaging favoring pneumonia, positive isolates
and multiple transfusions had significant association with mortality. Large scale
prospective studies are needed to determine the association of preemptive therapy
with higher mortality. The outcome of high risk FN in this study is favorable.
PMID- 28413793
TI - Pediatric hematological malignancy: Identification of issues involved in the road
to diagnosis.
AB - INTRODUCTION: Childhood malignancy, although a rare phenomenon, is still the
leading cause of mortality in the pediatric population. Early diagnosis and
treatment are imperative for the achievement of optimal prognosis. The study of
factors facilitating the delay in diagnosis is thus of utmost importance, to both
shorten the diagnostic delay and allow for early therapeutic intervention,
facilitating a higher prognosis. OBJECTIVE: To assess the referral pattern and
the identification of potential delays in the diagnosis of childhood malignancy
in a developing country. METHODOLOGY: The study was conducted in the Pediatric
Hematology and Oncology department of Sri Ramachandra University, Chennai, India.
The study included randomly selected 70 pediatric patients diagnosed with a
hematological malignancy, from July 2012-August 2013. The parents were
interviewed using a prepared questionnaire about patient symptomatology,
interaction with healthcare providers, final diagnosis, and referral details.
Data were statistically analyzed using Statistica(r) (STATsoft). RESULTS: 70
patients were included in the study (69% boys, 31% girls). The diagnostic delay
was primarily due to the delay experienced in the healthcare system, with a mean
delay of 26 days (Median: 18; Range: 5-39). Those from a lower socioeconomic
background and whom opted for a non-allopathic treatment approach experienced
higher diagnostic delays. Diagnostic time was significantly shorter for those who
visited a pediatrician versus the patients who visited a general physician or
super specialties (P = 0.043). CONCLUSIONS: Diagnostic delay is often associated
with an extensive disease presentation, an aggressive therapeutic approach, and
has a negative impact on patient prognosis. To lower mortality rate and
facilitate a favourable prognosis, diagnosis requires a high degree of clinical
suspicion and immediate intervention.
PMID- 28413794
TI - Comparative evaluation of iodine-131 metaiodobenzylguanidine and 18
fluorodeoxyglucose positron emission tomography in assessing neural crest tumors:
Will they play a complementary role?
AB - BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) has
established a role in the evaluation of several malignancies. However, its
precise clinical role in the neural crest cell tumors continues to evolve.
PURPOSE: The purpose of this study was to compare iodine-131
metaiodobenzylguanidine (131I-MIBG) and FDG-PET of head to head in patients with
neural crest tumors both qualitatively and semiquantitatively and to determine
their clinical utility in disease status evaluation and further management.
MATERIALS AND METHODS: A total of 32 patients who had undergone 131I-MIBG and FDG
PET prospectively were evaluated and clinicopathologically grouped into three
categories: neuroblastoma, pheochromocytoma, and medullary carcinoma thyroid.
RESULTS: In 18 patients of neuroblastoma, FDG PET and 131I-MIBG showed patient
specific sensitivity of 84% and 72%, respectively. The mean maximum standardized
uptake value (SUVmax) of primary lesions in patients with unfavorable histology
was found to be relatively higher than those with favorable histology (5.18 +/-
2.38 vs. 3.21 +/- 1.69). The mean SUVmaxof two common sites (posterior superior
iliac spine [PSIS] and greater trochanter) was higher in patients with involved
marrow than those with uninvolved one (2.36 and 2.75 vs. 1.26 and 1.34,
respectively). The ratio of SUVmaxof the involved/contralateral normal sites was
2.16 +/- 1.9. In equivocal bone marrow results, the uptake pattern with SUV
estimation can depict metastatic involvement and help in redirecting the biopsy
site. Among seven patients of pheochromocytoma, FDG-PET revealed 100% patient
specific sensitivity. FDG-PET detected more metastatic foci than 131I-MIBG (18
vs. 13 sites). In seven patients of medullary carcinoma thyroid, FDG-PET
localized residual, recurrent, or metastatic disease with much higher sensitivity
(32 metastatic foci with 72% patient specific sensitivity) than 131I-MIBG,
trending along the higher serum calcitonin levels. CONCLUSIONS: FDG-PET is not
only a good complementary modality in the management of neural crest cell tumors
but also it can even be superior, especially in cases of 131I-MIBG nonavid
tumors.
PMID- 28413795
TI - Opisthorchiasis, hypercholesterolemia, and cholangiocarcinoma: A reappraisal.
PMID- 28413796
TI - Duplicate publication and the need to strengthen editorial policy of the journal.
PMID- 28413797
TI - A rare case of brain metastasis in a patient with osteosarcoma.
PMID- 28413798
TI - Treatment planning challenges for prosthesis prostate cancer patients in
radiation therapy.
PMID- 28413799
TI - Lomustine induced acute pulmonary toxicity in a pediatric medulloblastoma
survivor.
PMID- 28413800
TI - Ineffective legislation affecting health of adolescents.
PMID- 28413801
TI - Fatty but starving marrow! Gelatinous transformation of bone marrow secondary to
plasma cell disorder and all-trans-retinoic acid therapy: A report of two cases.
PMID- 28413802
TI - First reported case of alveolar soft part sarcoma in constitutional mismatch
repair deficiency syndrome tumor spectrum - diagnosed in one of the siblings with
constitutional mismatch repair deficiency.
PMID- 28413803
TI - Epidemiology of burn injuries in Nepal: a systemic review.
AB - Burn is a global public health problem associated with significant morbidity and
mortality, mostly in low- and middle-income countries. Southeast-Asian countries
share a big burden of burn injuries, and Nepal is not an exception. We performed
a systemic review to examine the epidemiological characteristics of burn injures
in Nepal. Relevant epidemiological studies were identified through systemic
search in PubMed, EMBASE, and Google Scholar. Reference lists from relevant
review articles were also searched. Studies were included if they meet our
selection criteria. Eight studies were included in our systemic review. Most of
the burn victims belong to the working age group between 15-60 years old. Flame
burns were found to be the most common cause of burn injury followed by scald
burns, whereas scald burns were the most common cause of burn injury among the
pediatric population. Most patients sustained less severe burn injuries, with
home being the most common place of burn injury. The average hospital stay among
the burn victims ranged from 13 to 60 days. Mortality among the burn victims
ranged from 4.5 to 23.5%, with highest mortality among the flame burn patients.
Developed nations have significantly reduced the burn incidence through effective
intervention program. Although, burn injuries are the leading cause of morbidity
and mortality in Nepal, effective intervention programs are lacking due to the
limited epidemiological data related to burn injuries. Further large scale
research is imperative to investigate the problem and assess the effectiveness of
an intervention program.
PMID- 28413804
TI - Corneal compensation of presbyopia: PresbyLASIK: an updated review.
AB - ABSTRACT: The main purpose of this review is to compare and analyze the results
of the main PresbyLASIK approaches; central and peripheral. SUMMARY: A
comprehensive research was conducted in PUBMED using keywords like "presbyopia
correction", "PresbyLASIK", "Corneal multifocality", "Laser blended vision". We
reviewed the PresbyLASIK technique, uncorrected distance visual acuity (UDVA),
corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA),
and corrected near visual acuity (CNVA), and compared the differences between the
techniques.
PMID- 28413805
TI - Release of Airborne Polychlorinated Biphenyls from New Bedford Harbor Results in
Elevated Concentrations in the Surrounding Air.
AB - Qualitatively and quantitatively, we have demonstrated that airborne
polychlorinated biphenyl (PCB) concentrations in the air surrounding New Bedford
Harbor (NBH) are caused by its water PCB emissions. We measured airborne PCBs at
18 homes and businesses near NBH in 2015, with values ranging from 0.4 to 38 ng m
3, with a very strong Aroclor 1242/1016 signal that is most pronounced closest to
the harbor and reproducible over three sampling rounds. Using U.S. Environmental
Protection Agency (U.S. EPA) water PCB data from 2015 and local meteorology, we
predicted gas-phase fluxes of PCBs from 160 to 1200 MUg m-2 day-1. Fluxes were
used as emissions for AERMOD, a widely applied U.S. EPA atmospheric dispersion
model, to predict airborne PCB concentrations. The AERMOD predictions were within
a factor of 2 of the field measurements. PCB emission from NBH (110 kg year-1,
average 2015) is the largest reported source of airborne PCBs from natural waters
in North America, and the source of high ambient air PCB concentrations in
locations close to NBH. It is likely that NBH has been an important source of
airborne PCBs since it was contaminated with Aroclors more than 60 years ago.
PMID- 28413806
TI - Ryanodine and IP3 receptor-mediated calcium signaling play a pivotal role in
neurological infrared laser modulation.
AB - Pulsed infrared (IR) laser energy has been shown to modulate neurological
activity through both stimulation and inhibition of action potentials. While the
mechanism(s) behind this phenomenon is (are) not completely understood, certain
hypotheses suggest that the rise in temperature from IR exposure could activate
temperature- or pressure-sensitive ion channels or create pores in the cellular
outer membrane, allowing an influx of typically plasma-membrane-impermeant ions.
Studies using fluorescent intensity-based calcium ion ([Formula: see text])
sensitive dyes show changes in [Formula: see text] levels after various IR
stimulation parameters, which suggests that [Formula: see text] may originate
from the external solution. However, activation of intracellular signaling
pathways has also been demonstrated, indicating a more complex mechanism of
increasing intracellular [Formula: see text] concentration. We quantified the
[Formula: see text] mobilization in terms of influx from the external solution
and efflux from intracellular organelles using Fura-2 and a high-speed
ratiometric imaging system that rapidly alternates the dye excitation
wavelengths. Using nonexcitable Chinese hamster ovarian ([Formula: see text])
cells and neuroblastoma-glioma (NG108) cells, we demonstrate that intracellular
[Formula: see text] receptors play an important role in the IR-induced [Formula:
see text], with the [Formula: see text] response augmented by ryanodine receptors
in excitable cells.
PMID- 28413808
TI - Vessel tree tracking in angiographic sequences.
AB - We present a method to track vessels in angiography [contrast filled vessels in
two-dimensional (2-D) x-ray fluoroscopy]. Finding correspondence of a vessel tree
from consecutive angiogram frames provides significant value in computer-aided
clinical applications such as fast vessel tree segmentation, three-dimensional (3
D) vessel topology reconstruction from corresponding centerlines, cardiac motion
understanding, etc. However, establishing an accurate vessel tree correspondence
(vessel tree tracking) is a nontrivial problem due to nonlinear periodic cardiac
and breathing motion in 2-D views, foreshortening, false bifurcations due to 3-D
to 2-D projection, occlusion from other anatomies, etc. The vessel tree is
represented by BSpline curves. The control points of the BSpline curves are
landmarks that are the tracking targets. Our method maximizes the appearance
similarity while preserving the vessel structure. A directed acyclic graph (DAG)
is employed to represent the appearance and shape structure of the vessel tree:
nodes from the DAG encode the appearance of the vessel tree landmarks, and the
edges encode the relative locations between landmarks. The vessel tree tracking
problem turns into finding the most similar tree from the DAG in the next frame,
and it is solved using an efficient dynamic programming algorithm. We performed
evaluations on 62 x-ray angiography sequences (above 1000 frames). Experiment
results show our algorithm is robust to these challenges and delivers better
performance, compared to four existing methods.
PMID- 28413807
TI - From brain to blood vessels and back: a noninvasive optical imaging approach.
AB - The seminal work of Grinvald et al. has paved the way for the use of intrinsic
optical signals measured with reflection methods for the analysis of brain
function. Although this work has focused on the absorption signal associated with
deoxygenation, due to its detailed mapping ability and good signal-to-noise
ratio, Grinvald's group has also described other intrinsic signals related to
increased blood flow, scattering effects directly related to neural activation,
and pulsation effects related to arterial function. These intrinsic optical
signals can also be measured using noninvasive diffuse optical topographic and
tomographic imaging (DOT) methods that can be applied to humans. Here we compare
the reflection and DOT methods and the evidence for each type of intrinsic signal
in these two domains, with particular attention to work that has been conducted
in our laboratory. This work reveals the refined two-way relationship that exists
between vascular and neural phenomena in the brain: arterial health is related to
normal brain structure and function, both across individuals and across brain
regions within an individual, and neural function influences blood flow to
specific cortical regions. DOT methods can provide quantitative tools for
investigating these relationships in normal human subjects.
PMID- 28413810
TI - A subtle economy of time: Social media and the transformation of Indonesia's
Islamic preacher economy.
AB - The article is concerned with the latest developments in Indonesia's Islamic
field. Its focus is on the role of social media in exchange relationships between
Islamic preachers and their constituency. The article first discusses economic
exchanges between preachers and their followers, and then it concentrates on
social exchanges and how they are mediated today. Empirically, the article
delivers insight into the concerns of mostly female Indonesian middle-class
Muslims and shows how preachers have to adjust to the needs of their followers
who are regularly online. Theoretically, the article offers a rereading of Pierre
Bourdieu's classic work on forms of capital and their conversion. It emphasizes
the temporal dimension of capital accumulation and conversion and explores the
temporalities of online exchanges that have become constitutive of preacher
follower relationships. In doing so, it shows how Indonesia's Islamic preacher
economy is currently transformed by these online exchanges, resulting in preacher
follower relationships that are characterized by dialogic constructions of
Islamic authority. Being part of Indonesia's Islamic field, these changes in the
Islamic preacher economy point to a broader trend in Indonesia's Islamic field
toward greater sensitivity to the needs and worries of Indonesian middle-class
Muslims.
PMID- 28413809
TI - Preclinical imaging of iridocorneal angle and fundus using a modified integrated
flexible handheld probe.
AB - A flexible handheld imaging probe consisting of a [Formula: see text] charge
coupled device camera, light-emitting diode light sources, and near-infrared
laser source is designed and developed. The imaging probe is designed with
specifications to capture the iridocorneal angle images and posterior segment
images. Light propagation from the anterior chamber of the eye to the exterior is
considered analytically using Snell's law. Imaging of the iridocorneal angle
region and fundus is performed on ex vivo porcine samples and subsequently on
small laboratory animals, such as the New Zealand white rabbit and nonhuman
primate, in vivo. The integrated flexible handheld probe demonstrates high
repeatability in iridocorneal angle and fundus documentation. The proposed
concept and methodology are expected to find potential application in the
diagnosis, prognosis, and management of glaucoma.
PMID- 28413811
TI - Cell Surface Protein Detection to Assess Receptor Internalization.
AB - The migration of membrane receptors upon exposure to different
stimulants/inhibitors is of great importance. Among others, the internalization
of membrane receptors affects their accessibility to ligands and cell
responsiveness to environmental cues. Experimentally, receptor internalization
can be used as a measure of their activation. In our studies, we employed this
approach to explore cross-talk between a seven transmembrane domain receptor for
neuropeptide Y (NPY), Y5R, and a tyrosine kinase receptor for brain-derived
neurotrophic factor (BDNF), TrkB. To this end, we measured the internalization of
Y5R upon stimulation with the TrkB ligand, BDNF. Upon treatment with BDNF, the
cells were exposed to a membrane impermeable, biotinylation reagent that
selectively labels surface proteins. Subsequently, the biotinylated membrane
proteins were affinity-purified on columns with avidin resins and analyzed by
Western blot. Differences in the fraction of receptors present on the cell
surface of control and ligand-treated cells served as a measure of their
internalization and response to particular stimuli.
PMID- 28413812
TI - Quantitative 3D Time Lapse Imaging of Muscle Progenitors in Skeletal Muscle of
Live Mice.
AB - For non-optically clear mammalian tissues, it is now possible to use multi-photon
microscopy to penetrate deep into the tissue and obtain detailed single cell
images in a live animal, i.e., intravital imaging. This technique is in principle
applicable to any fluorescently marked cell, and we have employed it to observe
stem cells during the regenerative process. Stem cell-mediated skeletal muscle
regeneration in the mouse model has been classically studied at specific time
points by sacrificing the animal and harvesting the muscle tissue for downstream
analyses. A method for direct visualization of muscle stem cells to gain real
time information over a long period in a live mammal has been lacking. Here we
describe a step-by-step protocol adapted from Webster et al. (2016) to
quantitatively measure the behaviors of fluorescently labeled (GFP, EYFP) muscle
stem and progenitor cells during homeostasis as well as following muscle injury.
PMID- 28413815
TI - Data documenting the comparison between the theoretically expected values of free
sugars mass isotopomer composition with standards using GC-MS and LC-HRMS for
Metabolic Flux Analysis.
AB - The data presented in this article are related to the research article entitled
"13C labeling analysis of sugars by high resolution-mass spectrometry for
Metabolic Flux Analysis" (Acket et al., 2017) [1]. This article provides data
concerning the comparison between the theoretically expected values of free
sugars mass isotopomer composition with standards using our previous methods
using low resolution mass spectrometry by GC-MS (Koubaa et al., 2012, 2014)
[2,3], and your new method using high resolution-mass spectrometry (LC-HRMS) for
Metabolic Flux Analysis [1]. For discussion and a more comprehensive data
interpretation and analysis, please refer to Acket et al. (2017) [1].
PMID- 28413814
TI - Neural markers of individual differences in decision-making.
AB - In the last few years, neuroscientists have begun to identify associations
between individual differences in decision-making and features of neuroanatomy
and neurophysiology. Different tendencies in decision making, such as tolerance
for risk, delay or effort, have been linked to various neurobiological measures,
such as morphometry, structural connectivity, functional connectivity or the
function of neurotransmitter systems. Though far from immutable, these neural
features may nonetheless be suitable as relatively stable biomarkers for
different decision traits. The establishment of such markers would achieve one of
the stated goals of neuroeconomics, which is to improve the prediction of
economic behavior across different contexts.
PMID- 28413813
TI - New insights into early-life stress and behavioral outcomes.
AB - Adverse early-life experiences, including various forms of early-life stress,
have consistently been linked with vulnerability to cognitive and emotional
disorders later in life. Understanding the mechanisms underlying the enduring
consequences of early-life stress is an active area of research, because this
knowledge is critical for developing potential interventions. Animal models of
early-life stress typically rely on manipulating maternal/parental presence and
care, because these are the major source of early-life experiences in humans.
Diverse models have been created, and have resulted in a wealth of behavioral
outcomes. Here we focus on recent findings highlighting early-life stress-induced
behavioral disturbances, ranging from hippocampus-dependent memory deficits to
problems with experiencing pleasure (anhedonia). The use of naturalistic animal
models of chronic early-life stress provides insight into the spectrum of
cognitive and emotional outcomes and enables probing the underlying mechanisms
using molecular-, cellular-, and network-level approaches.
PMID- 28413816
TI - Spectroscopic and AFM characterization of polypeptide-surface interactions:
Controls and lipid quantitative analyses.
AB - This article is related to http://dx.doi.org/10.1016/j.bbamem.2017.01.005 (O.
Stromland, O.S. Handegard, M.L. Govasli, H. Wen, O. Halskau, 2017) [1]. In
protein and polypeptide-membrane interaction studies, negatively charged lipids
are often used as they are a known driver for membrane interaction. When using
fluorescence spectroscopy and CD as indicators of polypeptide binding and
conformational change, respectively, the effect of zwitterionic lipids only
should be documented. The present data documents several aspects of how two
engineered polypeptides (A-Cage-C and A-Lnk-C) derived from the membrane
associating protein alpha-Lactalbumin affects and are affected by the presence of
zwitterionic bilayers in the form of vesicles. We here document the behavior or
the Cage and Lnk segments with respect to membrane interaction and their residual
fold, using intrinsic tryptophan fluorescence assays. This data description also
documents the coverage of solid-supported bilayers prepared by spin-coating mica
using binary lipid mixes, a necessary step to ensure that AFM is performed on
areas that are covered by lipid bilayers when performing experiments. Uncovered
patches are detectable by both force curve measurements and height measurements.
We tested naked mica's ability to cause aggregation as seen by AFM, and found
this to be low compared to preparations containing negatively charged lipids.
Work with lipids also carries the risk of chemical degradation taking place
during vesicles preparation or other handling of the lipids. We therefor use 31P
NMR to quantify the head-group content of commonly used commercial extracts
before and after a standard protocol for vesicle production is applied.
PMID- 28413817
TI - Dataset in support of the generation of Niemann-Pick disease Type C1 patient
specific iPS cell lines carrying the novel NPC1 mutation c.1180T>C or the
prevalent c.3182T>C mutation - Analysis of pluripotency and neuronal
differentiation.
AB - Data presented in this article demonstrate the generation and characterization of
two novel Niemann-Pick disease Type C1 (NPC1) patient-specific induced
pluripotent stem cell (iPSC) lines, related to the research article Trilck et al.
(Diversity of Glycosphingolipid GM2 and Cholesterol Accumulation in NPC1 Patient
Specific iPSC-Derived Neurons; Brain Res.; 2017; 1657:52-61. doi:
10.1016/j.brainres.2016.11.031). For reprogramming fibroblasts, carrying the
novel homozygous mutation c.1180T>C and the prevalent homozygous mutation
c.3182T>C, were used. Reprogramming into patient-specific iPSCs was induced by
retroviral transduction of the transcription factors Sox2, Klf4, Oct4 and c-Myc,
and confirmed according to their pluripotency. The iPSCs were subsequently
differentiated into neural progenitor cells, which were terminally differentiated
into functional neurons and glial cells. The generation of these cell lines
provides further valuable tools to investigate pathogenic mechanism of NPC1 in
human neuronal cells carrying different NPC1 mutations.
PMID- 28413818
TI - Data on enhanced expression and purification of camelid single domain antibodies
from Escherichia coli classical inclusion bodies.
AB - Heterologous expression of high amounts of recombinant proteins is a milestone
for research and industrial purposes. Single domain antibodies (sdAbs) are heavy
chain only antibody fragments with applications in the biotechnological, medical
and industrial fields. The simple nature and small size of sdAbs allows for
efficient expression of the soluble molecule in different hosts. However, in some
cases, it results in low functional protein yield. To overcome this limitation,
expression of a 6xHistag sdAb was attempted in different conditions in
Escherichia coli BL21(DE3) cells. Data showed that high amount of sdAb can be
expressed in E. coli classical inclusion bodies, efficiently extracted by urea in
a short-time, and properly purified by metal ion affinity chromatography. These
data originate from the research article "Enhanced expression and purification of
camelid single domain VHH antibodies from classical inclusion bodies" Maggi and
Scotti (2017) [1] (DOI: http://dx.doi.org/10.1016/j.pep.2017.02.007).
PMID- 28413819
TI - Multisystemic Langerhans cell histiocytosis in an adult.
PMID- 28413820
TI - Coxsackievirus B5 associated with hand-foot-mouth disease in a healthy adult.
PMID- 28413821
TI - Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome.
AB - Down syndrome (DS), present in nearly six million people, is associated with an
extremely high risk to develop Alzheimer's disease (AD). Amyloid-beta and tau
pathology are omnipresent from age 40 years onward, but clinical symptoms do not
appear in all DS individuals. Dementia diagnostics is complex in this population,
illustrating the great need for predictive biomarkers. Although blood biomarkers
have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid
beta42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the
general population and are increasingly used in clinical practice. Surprisingly,
CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF
analyses would finally allow for the elucidation of its utility in (differential)
diagnoses and staging of disease severity. A sensitive and specific biomarker
profile for AD in DS would be of paramount importance to daily care, adaptive
caregiving, and specific therapeutic interventions.
PMID- 28413822
TI - Distinct Neural Properties in the Low-Frequency Region of the Chicken Cochlear
Nucleus Magnocellularis.
AB - Topography in the avian cochlear nucleus magnocellularis (NM) is represented as
gradually increasing characteristic frequency (CF) along the caudolateral-to
rostromedial axis. In this study, we characterized the organization and cell
biophysics of the caudolateral NM (NMc) in chickens (Gallus gallus). Examination
of cellular and dendritic architecture first revealed that NMc contains small
neurons and extensive dendritic processes, in contrast to adendritic, large
neurons located more rostromedially. Individual dye-filling study further
demonstrated that NMc is divided into two subregions, with NMc2 neurons having
larger and more complex dendritic fields than NMc1. Axonal tract tracing studies
confirmed that NMc1 and NMc2 neurons receive afferent inputs from the auditory
nerve and the superior olivary nucleus, similar to the adendritic NM. However,
the auditory axons synapse with NMc neurons via small bouton-like terminals,
unlike the large end bulb synapses on adendritic NM neurons. Immunocytochemistry
demonstrated that most NMc2 neurons express cholecystokinin but not calretinin,
distinct from NMc1 and adendritic NM neurons that are cholecystokinin negative
and mostly calretinin positive. Finally, whole-cell current clamp recordings
revealed that NMc neurons require significantly lower threshold current for
action potential generation than adendritic NM neurons. Moreover, in contrast to
adendritic NM neurons that generate a single-onset action potential, NMc neurons
generate multiple action potentials to suprathreshold sustained depolarization.
Taken together, our data indicate that NMc contains multiple neuron types that
are structurally, connectively, molecularly, and physiologically different from
traditionally defined NM neurons, emphasizing specialized neural properties for
processing low-frequency sounds.
PMID- 28413823
TI - Long-Term Predictive and Feedback Encoding of Motor Signals in the Simple Spike
Discharge of Purkinje Cells.
AB - Most hypotheses of cerebellar function emphasize a role in real-time control of
movements. However, the cerebellum's use of current information to adjust future
movements and its involvement in sequencing, working memory, and attention argues
for predicting and maintaining information over extended time windows. The
present study examines the time course of Purkinje cell discharge modulation in
the monkey (Macaca mulatta) during manual, pseudo-random tracking. Analysis of
the simple spike firing from 183 Purkinje cells during tracking reveals
modulation up to 2 s before and after kinematics and position error. Modulation
significance was assessed against trial shuffled firing, which decoupled simple
spike activity from behavior and abolished long-range encoding while preserving
data statistics. Position, velocity, and position errors have the most frequent
and strongest long-range feedforward and feedback modulations, with less common,
weaker long-term correlations for speed and radial error. Position, velocity, and
position errors can be decoded from the population simple spike firing with
considerable accuracy for even the longest predictive (-2000 to -1500 ms) and
feedback (1500 to 2000 ms) epochs. Separate analysis of the simple spike firing
in the initial hold period preceding tracking shows similar long-range
feedforward encoding of the upcoming movement and in the final hold period
feedback encoding of the just completed movement, respectively. Complex spike
analysis reveals little long-term modulation with behavior. We conclude that
Purkinje cell simple spike discharge includes short- and long-range
representations of both upcoming and preceding behavior that could underlie
cerebellar involvement in error correction, working memory, and sequencing.
PMID- 28413824
TI - Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic
Neuronal Circuitry.
AB - Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the
fine-tuning of neuron development and the establishment of wiring patterns in the
brain. However, whether serotonin is involved in the maintenance of neuronal
circuitry in the adult brain remains elusive. Here, we use a Tph2fl degrees x
conditional knockout (cKO) mouse line to assess the impact of serotonin depletion
during adulthood on serotonergic system organization. Data show that the density
of serotonergic fibers is increased in the hippocampus and decreased in the
thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin
depletion. Strikingly, these defects are rescued following reestablishment of
brain 5-HT signaling via administration of the serotonin precursor 5
hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers
reveals that changes in serotonin homeostasis affect axonal branching complexity.
These data demonstrate that maintaining proper serotonin homeostasis in the adult
brain is crucial to preserve the correct serotonergic axonal wiring.
PMID- 28413825
TI - Color-Change Detection Activity in the Primate Superior Colliculus.
AB - The primate superior colliculus (SC) is a midbrain structure that participates in
the control of spatial attention. Previous studies examining the role of the SC
in attention have mostly used luminance-based visual features (e.g., motion,
contrast) as the stimuli and saccadic eye movements as the behavioral response,
both of which are known to modulate the activity of SC neurons. To explore the
limits of the SC's involvement in the control of spatial attention, we recorded
SC neuronal activity during a task using color, a visual feature dimension not
traditionally associated with the SC, and required monkeys to detect threshold
level changes in the saturation of a cued stimulus by releasing a joystick during
maintained fixation. Using this color-based spatial attention task, we found
substantial cue-related modulation in all categories of visually responsive
neurons in the intermediate layers of the SC. Notably, near-threshold changes in
color saturation, both increases and decreases, evoked phasic bursts of activity
with magnitudes as large as those evoked by stimulus onset. This change-detection
activity had two distinctive features: activity for hits was larger than for
misses, and the timing of change-detection activity accounted for 67% of joystick
release latency, even though it preceded the release by at least 200 ms. We
conclude that during attention tasks, SC activity denotes the behavioral
relevance of the stimulus regardless of feature dimension and that phasic event
related SC activity is suitable to guide the selection of manual responses as
well as saccadic eye movements.
PMID- 28413826
TI - Medial Ganglionic Eminence Progenitors Transplanted into Hippocampus Integrate in
a Functional and Subtype-Appropriate Manner.
AB - Medial ganglionic eminence (MGE) transplantation rescues disease phenotypes in
various preclinical models with interneuron deficiency or dysfunction, including
epilepsy. While underlying mechanism(s) remains unclear to date, a simple
explanation is that appropriate synaptic integration of MGE-derived interneurons
elevates GABA-mediated inhibition and modifies the firing activity of excitatory
neurons in the host brain. However, given the complexity of interneurons and
potential for transplant-derived interneurons to integrate or alter the host
network in unexpected ways, it remains unexplored whether synaptic connections
formed by transplant-derived interneurons safely mirror those associated with
endogenous interneurons. Here, we combined optogenetics, interneuron-specific Cre
driver mouse lines, and electrophysiology to study synaptic integration of MGE
progenitors. We demonstrated that MGE-derived interneurons, when transplanted
into the hippocampus of neonatal mice, migrate in the host brain, differentiate
to mature inhibitory interneurons, and form appropriate synaptic connections with
native pyramidal neurons. Endogenous and transplant-derived MGE progenitors
preferentially formed inhibitory synaptic connections onto pyramidal neurons but
not endogenous interneurons. These findings demonstrate that transplanted MGE
progenitors functionally integrate into the postnatal hippocampal network.
PMID- 28413827
TI - A Balanced Comparison of Object Invariances in Monkey IT Neurons.
AB - Our ability to recognize objects across variations in size, position, or rotation
is based on invariant object representations in higher visual cortex. However, we
know little about how these invariances are related. Are some invariances harder
than others? Do some invariances arise faster than others? These comparisons can
be made only upon equating image changes across transformations. Here, we
targeted invariant neural representations in the monkey inferotemporal (IT)
cortex using object images with balanced changes in size, position, and rotation.
Across the recorded population, IT neurons generalized across size and position
both stronger and faster than to rotations in the image plane as well as in
depth. We obtained a similar ordering of invariances in deep neural networks but
not in low-level visual representations. Thus, invariant neural representations
dynamically evolve in a temporal order reflective of their underlying
computational complexity.
PMID- 28413829
TI - Prioritizing US Cervical Cancer Prevention With Results From a Geospatial Model.
AB - PURPOSE: To determine if differences in screening and vaccination patterns across
the population may accentuate ethnic and geographic variation in future burden of
disease. METHODS: Using Cancer in North America data provided by the North
American Association of Central Cancer Registries, county cervical cancer
incidence trends from 1995 to 2009 were modeled for the entire United States
using ecologic covariates. Rates for health service areas were also modeled by
ethnicity. State-level incidence was mapped together with Papanicolaou (Pap)
screening, past 3 years (women >= 18 years old), and three-dose human
papillomavirus (HPV) vaccine coverage (girls 13 to 17 years old) to identify
potential priority areas for preventive services. RESULTS: US cervical cancer
incidence decreased more during the periods 1995 to 1999 and 2000 to 2004 than
during the period 2005 to 2009. During these 15 years, the most affected areas
became increasingly confined to Appalachia, the lower Mississippi Valley, the
Deep South, Texas, and Florida. Hispanic and black women experienced a higher
incidence of cervical cancer than both white and Asian and Pacific Islander women
during each period. Women in 10 of 17 states/districts with a high incidence (>=
8.14/100,000) reported low Pap testing (< 78.5%), HPV vaccine coverage (< 33.9%),
or both prevention technologies. CONCLUSION: The decline in cervical cancer
incidence has slowed in recent years. Access to HPV vaccination, targeted
screening, and treatment in affected populations is needed to reduce cervical
cancer disparities in the future.
PMID- 28413830
TI - An observational study on surgically treated adult idiopathic scoliosis patients'
quality of life outcomes at 1- and 2-year follow-ups and comparison to controls.
AB - BACKGROUND: Prospective data on health-related quality of life in patients with
idiopathic scoliosis treated surgically as adults is needed. We compared
preoperative and 1- and 2-year follow-up data in surgically treated adults with
idiopathic scoliosis with juvenile or adolescent onset. Results were compared to
untreated adults with scoliosis and population normative data. METHODS: A
comparison of preoperative and 1- and 2-year follow-up data of 75 adults
surgically treated for idiopathic scoliosis at a mean age of 28 years (range 18
to 69) from a prospective national register study, as well as a comparison with
age- and sex-matched data from 75 untreated adults with less severe scoliosis and
75 adults without scoliosis, was made. Outcome measures were EuroQol-5 dimensions
(EQ-5D) and Scoliosis Research Society (SRS)-22r questionnaire. RESULTS: In the
surgically treated, EQ-5D and SRS-22r scores had statistically significant
improvements at both 1- and 2-year follow-ups (all p < 0.015). The effect size
of surgery on EQ-5D at 1-year follow-up was large (r = -0.54) and small-medium (r
= -0.20) at 2-year follow-up. The effect size of surgery on SRS-22r outcomes was
medium-large at 1- and 2-year follow-ups (r = -0.43 and r = -0.42 respectively).
At the 2-year follow-up, the EQ-5D score and the SRS-22r subscore were similar to
the untreated scoliosis group (p = 0.56 and p = 0.91 respectively), but lower
than those in the adults without scoliosis (p < 0.001 for both comparisons).
CONCLUSIONS: Adults with idiopathic scoliosis experience an increase in health
related quality of life following surgery at 2-year follow-up, approaching the
health-related quality of life of untreated individuals with less severe
scoliosis, but remain lower than normative population data.
PMID- 28413828
TI - Functions and Mechanisms of Sleep.
AB - Sleep is a complex physiological process that is regulated globally, regionally,
and locally by both cellular and molecular mechanisms. It occurs to some extent
in all animals, although sleep expression in lower animals may be co-extensive
with rest. Sleep regulation plays an intrinsic part in many behavioral and
physiological functions. Currently, all researchers agree there is no single
physiological role sleep serves. Nevertheless, it is quite evident that sleep is
essential for many vital functions including development, energy conservation,
brain waste clearance, modulation of immune responses, cognition, performance,
vigilance, disease, and psychological state. This review details the
physiological processes involved in sleep regulation and the possible functions
that sleep may serve. This description of the brain circuitry, cell types, and
molecules involved in sleep regulation is intended to further the reader's
understanding of the functions of sleep.
PMID- 28413831
TI - Differential ability of the dorsal and ventral rat hippocampus to exhibit group I
metabotropic glutamate receptor-dependent synaptic and intrinsic plasticity.
AB - BACKGROUND: The hippocampus is critically involved in learning and memory
processes. Although once considered a relatively homogenous structure, it is now
clear that the hippocampus can be divided along its longitudinal axis into
functionally distinct domains, responsible for the encoding of different types of
memory or behaviour. Although differences in extrinsic connectivity are likely to
contribute to this functional differentiation, emerging evidence now suggests
that cellular and molecular differences at the level of local hippocampal
circuits may also play a role. METHODS: In this study, we have used extracellular
field potential recordings to compare basal input/output function and group I
metabotropic glutamate receptor-dependent forms of synaptic and intrinsic
plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the
adult rat hippocampus. RESULTS: Using two extracellular electrodes to
simultaneously record field EPSPs and population spikes, we show that dorsal and
ventral hippocampal slices differ in their basal levels of excitatory synaptic
transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore,
we show that slices taken from the ventral hippocampus have a greater ability
than their dorsal counterparts to exhibit long-term depression of synaptic
transmission and EPSP-to-Spike potentiation induced by transient application of
the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine. CONCLUSIONS: Together,
our results provide further evidence that the information processing properties
of local hippocampal circuits differ in the dorsal and ventral hippocampal
sectors, and that these differences may in turn contribute to the functional
differentiation that exists along the hippocampal longitudinal axis.
PMID- 28413832
TI - Statistical analysis plan for the WOMAN-ETAPlaT study: Effect of tranexamic acid
on platelet function and thrombin generation.
AB - Background. Postpartum haemorrhage (PPH) is a potentially life-threatening
complication for women, and the leading cause of maternal mortality. Tranexamic
acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and
to reduce blood loss in general surgery. TXA may have effects on thrombin
generation, platelet function and coagulation factors as a result of its
inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World
Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically
diagnosed with PPH after a vaginal delivery or caesarean section, are eligible
for inclusion in the study. Blood samples will be collected at the baseline and
30 minutes after the first dose of study treatment is given. Platelet function
will be evaluated in whole blood immediately after sampling with Multiplate(r)
tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and
coagulation factors vW, V and VIII will be analysed using platelet poor plasma.
Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on
13 January 2015, during this time 188 patients were recruited. The final
participant follow-up was completed on 04 March 2015. This article introduces the
statistical analysis plan for the study, without reference to unblinded data.
Conclusion. The data from this study will provide evidence for the effect of TXA
on thrombin generation, platelet function and coagulation factors in women with
PPH. Trial registration: ClinicalTrials.gov Identifier: NCT00872469;
ISRCTN76912190.
PMID- 28413834
TI - Synthesis and characterization of zinc oxide thin films for optoelectronic
applications.
AB - Micro-ring structured zinc oxide (ZnO) thin films were prepared on glass
substrates by spray pyrolysis and their structural, morphological, optical and
electrical properties were investigated. X-ray Diffraction (XRD) analysis
revealed the films' hexagonal wurtzite phase with a preferred (002) grain
orientation. The mean crystallite size calculated on the basis of the Debye
Scherrer model was 24 nm and a small dislocation density of [Formula: see text]
was obtained, indicating the existence of few lattice defects and good
crystallinity. Scanning Electron Microscopy (SEM) micrographs revealed the film's
granular nature composed of rod-shaped and spherical nanoparticles which
agglomerated to form micro-ring like film clusters on the film surface. The
average transmittance in the visible region, optical band gap and Urbach energy
were approximately 75-80%, 3.28 eV and 57 meV, respectively. The refractive index
and extinction coefficient were determined using Swanepoel's envelope method.
Raman spectroscopy revealed the presence of small amounts of residual tensile
stress and low density of defects in the ZnO thin films. This was consistent with
XRD analysis. A low sheet resistivity [Formula: see text] and high figure of
merit [Formula: see text] were obtained for our films indicating their
suitability in optoelectronic applications.
PMID- 28413833
TI - Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on
motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse
model of Alzheimer's disease.
AB - Alzheimer's disease (AD), a progressive neurodegenerative disorder, is linked to
oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau
hyperphosphorylation and the accumulation of amyloid-beta (Abeta) plaques and
neurofibrillary tangles (NFT). A growing body of evidence suggests that
mitochondrial dysfunction can be a key promoter of all of these pathologies and
predicts that restoration of mitochondrial function might be a potential
therapeutic strategy for AD. Therefore, in the present study, we tested the
beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II),
containing NT020 (a mitochondrial restorative and antioxidant proprietary
formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria
biogenesis) in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks,
starting at 3 months of age, after which behavioral and neuropathological
endpoints were determined. The data from behavioral test batteries clearly
revealed that dietary supplementation of Nutra II effectively ameliorated the
motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II
also protected mitochondrial function in 5XFAD mice brain, as evidenced by
declined ROS levels and membrane hyperpolarization, together with elevated ATP
levels and respiratory states. Interestingly, while Nutra II treatment only
slightly reduced soluble Abeta42 levels, this formulation significantly impacted
tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD
mouse brain. Taken together, these preclinical findings confirm that
mitochondrial function may be a key treatment target for AD and that Nutra II
should be further investigated as a potential candidate for AD therapy.
PMID- 28413836
TI - Assessment of the perceived effects and management challenges of Mikania
micrantha invasion in Chitwan National Park buffer zone community forest, Nepal.
AB - The effects of invasion by Mikania micrantha in the buffer zone of Chitwan
National Park (CNP) of Nepal are well documented; however the studies were
confined to appraising the perception of household and did not assess the changes
in livelihood activities after the invasion. This study presents the effects of
invasion of M. micrantha on the livelihood of buffer zone of the Chitwan National
Park; hence addressing the gap in information and shows the complex effect of M.
micrantha on rural livelihood. The study used a questionnaire survey to 170
households in the CNP of Nepal. The results indicate that the invasion of M.
micrantha have negative effects on the community livelihood in the study area.
Basic forest products such as fodder and fuel wood have become scarce as a result
of reduction in the native plants. Also the spread of M. micrantha is creating
impassable copse that destroy wildlife abode and jungle paths resulting into
animals to shift their habitat to core area thereby reducing tourism revenues.
Therefore, the study concludes that invasion of M. micrantha directly or
indirectly is modifying the rural household livelihoods and a quick action is
stipulated. Hence, a higher level body like the Ministry of Forestry or
Department of National Park and Wildlife Conservation needs to take care of
issues related to alien species. Correspondingly, it is also very important that
people are aware and educated about alien species and their effects.
PMID- 28413835
TI - miRNA signatures can predict acute liver failure in hepatitis E infected pregnant
females.
AB - BACKGROUND: Acute viral hepatitis E (AVH-E) can often result in acute liver
failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced
liver failure. We investigated their role as a biomarker in predicting ALF due to
HEV (ALF-E). METHODS: We performed next generation sequencing and subsequent
validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV
(ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy
controls. FINDINGS: Eleven microRNAs were significantly expressed in response to
HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly
expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but
not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting
AVH-E in pregnant females. miR-450b which affects cellular proliferation and
metabolic processes through RNF20 and SECB was predominanlty upregulated and
correlated with poor outcome (ROC 0.958, p = 0.001). INTERPRETATION: Our results
reveal that a specific microRNA profile can predict fatality in ALF-E in
pregnancy. These microRNAs could be exploited as prognostic biomarkers and help
in the development of new therapeutic interventions.
PMID- 28413837
TI - Familial exudative vitreoretinopathy presentation as persistent fetal
vasculature.
AB - PURPOSE: To illustrate a presentation of familial exudative vitreoretinopathy
(FEVR) that can be mistaken for unilateral persistent fetal vasculature (PFV) and
the importance of wide angle fluorescein angiography in making this distinction.
A patient was referred with a unilateral retrolental membrane and retinal
detachment from PFV but was found to have FEVR. OBSERVATIONS: A 4 month-old full
term infant was referred with the diagnosis of PFV based on findings of a dense
retrolental membrane and microphthalmia in the left eye. The patient had a near
complete retinal detachment with some exudation. Wide-field fluorescein
angiography of the right eye revealed avascular retina and leakage at the
vascular/avascular junction. Genetic testing confirmed a mutation in FZD4,
supporting the clinical diagnosis of FEVR. Prompt laser therapy to the avascular
area in the right eye was performed and lensectomy/vitrectomy with membrane
dissection was performed in the left eye. CONCLUSIONS AND IMPORTANCE: FEVR can
present with great variability between eyes. In patients presenting with findings
suggestive of PFV, careful bilateral examination with wide-field fluorescein
angiography is helpful. Early diagnosis and treatment are important to preserve
visual acuity, especially in the less affected eye.
PMID- 28413838
TI - Advanced structural multimodal imaging of a patient with subcortical band
heterotopia.
AB - Subcortical band heterotopia (SBH) is a disorder of neuronal migration most
commonly due to mutations of the Doublecortin (DCX) gene. A range of phenotypes
is seen, with most patients having some degree of epilepsy and intellectual
disability. Advanced diffusion and structural magnetic resonance imaging (MRI)
sequences may be useful in identifying heterotopias and dysplasias of different
sizes in drug-resistant epilepsy. We describe a patient with SBH and drug
resistant epilepsy and investigate neurite density, neurite dispersion, and
diffusion parameters as compared to a healthy control through the use of multiple
advanced MRI modalities. Neurite density and dispersion in heterotopia was found
to be more similar to white matter than gray matter. Neurite density and
dispersion maps obtained using diffusion imaging may be able to better
characterize different subtypes of heterotopia.
PMID- 28413839
TI - Modeling Reusable and Interoperable Faceted Browsing Systems with Category
Theory.
AB - Faceted browsing has become ubiquitous with modern digital libraries and online
search engines, yet the process is still difficult to abstractly model in a
manner that supports the development of interoperable and reusable interfaces. We
propose category theory as a theoretical foundation for faceted browsing and
demonstrate how the interactive process can be mathematically abstracted.
Existing efforts in facet modeling are based upon set theory, formal concept
analysis, and lightweight ontologies, but in many regards, they are
implementations of faceted browsing rather than a specification of the basic,
underlying structures and interactions. We will demonstrate that category theory
allows us to specify faceted objects and study the relationships and interactions
within a faceted browsing system. Implementations can then be constructed through
a category-theoretic lens using these models, allowing abstract comparison and
communication that naturally support interoperability and reuse.
PMID- 28413840
TI - Modeling Integration and Reuse of Heterogeneous Terminologies in Faceted Browsing
Systems.
AB - We integrate heterogeneous terminologies into our category-theoretic model of
faceted browsing and show that existing terminologies and vocabularies can be
reused as facets in a cohesive, interactive system. Commonly found in online
search engines and digital libraries, faceted browsing systems depend upon one or
more taxonomies which outline the structure and content of the facets available
for user interaction. Controlled vocabularies or terminologies are often
externally curated and are available as a reusable resource across systems. We
demonstrated previously that category theory can abstractly model faceted
browsing in a way that supports the development of interfaces capable of reusing
and integrating multiple models of faceted browsing. We extend this model by
illustrating that terminologies can be reused and integrated as facets across
systems with examples from the biomedical domain.
PMID- 28413841
TI - Correlation of electrode position and clinical outcomes in globus pallidus
stimulation for dystonia.
AB - BACKGROUND: The correlation between the electrode location and the clinical
outcome for internal globus pallidus (GPi) deep brain stimulation (DBS) has not
been fully elucidated. OBJECTIVE: The aim of this study was to determine the
discrepancies between the theoretical target planned by magnetic resonance
imaging (MRI) and the actual electrode location in postoperative MRI, as well as
to find the correlation between the final electrode locations and the clinical
outcome after GPi DBS. METHODS: Thirty-six patients who underwent GPi DBS for
dystonia were included in this retrospective study. The X coordinate was defined
as the lateral distance from the midline, the Y coordinate as the anterior
distance from the midcommissural point, and the Z coordinate as the inferior
distance from the intercommissural line. RESULTS: All coordinates showed a
significant difference between theoretical and actual values for all electrode
locations (p < 0.05). In particular, greater differences were exhibited for Y
than for the X and Z coordinates. There was no significant difference in the
accuracy of the localization of the left-side versus the right-side electrode for
any coordinates. The patients whose electrodes were located within or near the
posteroventral GPi showed better clinical outcomes. CONCLUSIONS: The actual
electrode location was slightly more posterior to the theoretically planned
target. Electrodes concentrated near the posteroventral GPi tended to yield
favorable outcomes.
PMID- 28413842
TI - "I do not have time. Is there a handout I can use?": combining physicians' needs
and behavior change theory to put physical activity evidence into practice.
AB - : Guidelines for physical activity exist and following them would improve health.
Physicians can advise patients on physical activity. We found barriers related to
physicians' knowledge, a lack of tools and of physician incentives, and competing
demands for limited time with a patient. We discuss interventions that could
reduce these barriers. INTRODUCTION: Uptake of physical activity (PA) guidelines
would improve health and reduce mortality in older adults. However, physicians
face barriers in guideline implementation, particularly when faced with needing
to tailor recommendations in the presence of chronic disease. We performed a
behavioral analysis of physician barriers to PA guideline implementation and to
identify interventions. The Too Fit To Fracture physical activity recommendations
were used as an example of disease-specific PA guidelines. METHODS: Focus groups
and semi-structured interviews were conducted with physicians and nurse
practitioners in Ontario, stratified by type of physician, geographic area, and
urban/rural, and transcribed verbatim. Two researchers coded data and identified
emerging themes. Using the behavior change wheel framework, themes were
categorized into capability, opportunity and motivation, and interventions were
identified. RESULTS: Fifty-nine family physicians, specialists, and nurse
practitioners participated. Barriers were as follows: Capability-lack of exercise
knowledge or where to refer; Opportunity-pragmatic tools, fit within existing
workflow, available programs that meet patients' needs, physical activity
literacy and cultural practices; Motivation-lack of incentives, not in their
scope of practice or professional identity, competing priorities, outcome
expectancies. Interventions selected: education, environmental restructuring,
enablement, persuasion. Policy categories: communications/marketing, service
provision, guidelines. CONCLUSIONS: Key barriers to PA guideline implementation
among physicians include knowledge on where to refer or what to say, access to
pragmatic programs or resources, and things that influence motivation, such as
competing priorities or lack of incentives. Future work will report on the
development and evaluation of knowledge translation interventions informed by the
barriers.
PMID- 28413843
TI - Methodology Used to Assess Acceptability of Oral Pediatric Medicines: A
Systematic Literature Search and Narrative Review.
AB - BACKGROUND: Regulatory guidelines require that any new medicine designed for a
pediatric population must be demonstrated as being acceptable to that population.
There is currently no guidance on how to conduct or report on acceptability
testing. AIM: Our objective was to undertake a review of the methods used to
assess the acceptability of medicines within a pediatric population and use this
review to propose the most appropriate methodology. METHODS: We used a defined
search strategy to identify literature reports of acceptability assessments of
medicines conducted within pediatric populations and extracted information about
the tools used in these studies for comparison across studies. RESULTS: In total,
61 articles were included in the analysis. Palatability was the most common
(54/61) attribute measured when evaluating acceptability. Simple scale methods
were most commonly used, with visual analog scales (VAS) and hedonic scales used
both separately and in combination in 34 of the 61 studies. Hedonic scales alone
were used in 14 studies and VAS alone in just five studies. Other tools included
Likert scales; forced choice or preference; surveys or questionnaires;
observations of facial expressions during administration, ease of swallowing, or
ability to swallow the dosage; prevalence of complaints or refusal to take the
medicine; and time taken for a nurse to administer the medicine. CONCLUSIONS: The
best scale in terms of validity, reliability, feasibility, and preference to use
when assessing acceptability remains unclear. Further work is required to select
the most appropriate method to justify whether a medicine is acceptable to a
pediatric population.
PMID- 28413844
TI - Organo-axial volvulus of the small intestine: radiological case report and
consideration for its mechanism.
AB - Gastrointestinal volvulus is mainly classified into two subtypes, mesentero-axial
volvulus and organo-axial volvulus. The detailed imaging findings of organo-axial
volvulus of the small intestine have never been reported as far as we know. In
this article, we report a case of organo-axial volvulus of the small intestine,
focusing on the computed tomography (CT) findings. An 80-year-old man was
radiologically diagnosed as having organo-axial volvulus of the terminal ileum
and it was confirmed by open surgery without adhesion or any other anatomical
abnormalities. CT showed two specific findings, split-bowel sign and rotating-C
sign, which we think reflect pathophysiologic features of organo-axial volvulus.
We think the pathogenic mechanism of organo-axial volvulus can be explained by
the convergence of the reversed-rotational twist following the formation of a
twisted but non-obstructive circular loop, even if there is no adhesion.
Radiologists should be aware that organo-axial volvulus can occur even in the
small intestine, and in the case of small bowel obstruction with single
transition point, the two pathophysiologic signs mentioned above must be looked
for to diagnose the possibility of organo-axial volvulus.
PMID- 28413845
TI - Carbon uptake by mature Amazon forests has mitigated Amazon nations' carbon
emissions.
AB - BACKGROUND: Several independent lines of evidence suggest that Amazon forests
have provided a significant carbon sink service, and also that the Amazon carbon
sink in intact, mature forests may now be threatened as a result of different
processes. There has however been no work done to quantify non-land-use-change
forest carbon fluxes on a national basis within Amazonia, or to place these
national fluxes and their possible changes in the context of the major
anthropogenic carbon fluxes in the region. Here we present a first attempt to
interpret results from ground-based monitoring of mature forest carbon fluxes in
a biogeographically, politically, and temporally differentiated way.
Specifically, using results from a large long-term network of forest plots, we
estimate the Amazon biomass carbon balance over the last three decades for the
different regions and nine nations of Amazonia, and evaluate the magnitude and
trajectory of these differentiated balances in relation to major national
anthropogenic carbon emissions. RESULTS: The sink of carbon into mature forests
has been remarkably geographically ubiquitous across Amazonia, being substantial
and persistent in each of the five biogeographic regions within Amazonia. Between
1980 and 2010, it has more than mitigated the fossil fuel emissions of every
single national economy, except that of Venezuela. For most nations (Bolivia,
Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname) the sink has probably
additionally mitigated all anthropogenic carbon emissions due to Amazon
deforestation and other land use change. While the sink has weakened in some
regions since 2000, our analysis suggests that Amazon nations which are able to
conserve large areas of natural and semi-natural landscape still contribute
globally-significant carbon sequestration. CONCLUSIONS: Mature forests across all
of Amazonia have contributed significantly to mitigating climate change for
decades. Yet Amazon nations have not directly benefited from providing this
global scale ecosystem service. We suggest that better monitoring and reporting
of the carbon fluxes within mature forests, and understanding the drivers of
changes in their balance, must become national, as well as international,
priorities.
PMID- 28413846
TI - A carbon balance model for the great dismal swamp ecosystem.
AB - BACKGROUND: Carbon storage potential has become an important consideration for
land management and planning in the United States. The ability to assess
ecosystem carbon balance can help land managers understand the benefits and
tradeoffs between different management strategies. This paper demonstrates an
application of the Land Use and Carbon Scenario Simulator (LUCAS) model developed
for local-scale land management at the Great Dismal Swamp National Wildlife
Refuge. We estimate the net ecosystem carbon balance by considering past
ecosystem disturbances resulting from storm damage, fire, and land management
actions including hydrologic inundation, vegetation clearing, and replanting.
RESULTS: We modeled the annual ecosystem carbon stock and flow rates for the 30
year historic time period of 1985-2015, using age-structured forest growth curves
and known data for disturbance events and management activities. The 30-year
total net ecosystem production was estimated to be a net sink of 0.97 Tg C. When
a hurricane and six historic fire events were considered in the simulation, the
Great Dismal Swamp became a net source of 0.89 Tg C. The cumulative above and
below-ground carbon loss estimated from the South One and Lateral West fire
events totaled 1.70 Tg C, while management activities removed an additional 0.01
Tg C. The carbon loss in below-ground biomass alone totaled 1.38 Tg C, with the
balance (0.31 Tg C) coming from above-ground biomass and detritus. CONCLUSIONS:
Natural disturbances substantially impact net ecosystem carbon balance in the
Great Dismal Swamp. Through alternative management actions such as re-wetting,
below-ground biomass loss may have been avoided, resulting in the added carbon
storage capacity of 1.38 Tg. Based on two model assumptions used to simulate the
peat system, (a burn scar totaling 70 cm in depth, and the soil carbon
accumulation rate of 0.36 t C/ha-1/year-1 for Atlantic white cedar), the total
soil carbon loss from the South One and Lateral West fires would take
approximately 1740 years to re-amass. Due to the impractical time horizon this
presents for land managers, this particular loss is considered permanent. Going
forward, the baseline carbon stock and flow parameters presented here will be
used as reference conditions to model future scenarios of land management and
disturbance.
PMID- 28413847
TI - Greenhouse gas emissions from tropical forest degradation: an underestimated
source.
AB - BACKGROUND: The degradation of forests in developing countries, particularly
those within tropical and subtropical latitudes, is perceived to be an important
contributor to global greenhouse gas emissions. However, the impacts of forest
degradation are understudied and poorly understood, largely because international
emission reduction programs have focused on deforestation, which is easier to
detect and thus more readily monitored. To better understand and seize
opportunities for addressing climate change it will be essential to improve
knowledge of greenhouse gas emissions from forest degradation. RESULTS: Here we
provide a consistent estimation of forest degradation emissions between 2005 and
2010 across 74 developing countries covering 2.2 billion hectares of forests. We
estimated annual emissions of 2.1 billion tons of carbon dioxide, of which 53%
were derived from timber harvest, 30% from woodfuel harvest and 17% from forest
fire. These percentages differed by region: timber harvest was as high as 69% in
South and Central America and just 31% in Africa; woodfuel harvest was 35% in
Asia, and just 10% in South and Central America; and fire ranged from 33% in
Africa to only 5% in Asia. Of the total emissions from deforestation and forest
degradation, forest degradation accounted for 25%. In 28 of the 74 countries,
emissions from forest degradation exceeded those from deforestation. CONCLUSIONS:
The results of this study clearly demonstrate the importance of accounting
greenhouse gases from forest degradation by human activities. The scale of
emissions presented indicates that the exclusion of forest degradation from
national and international GHG accounting is distorting. This work helps identify
where emissions are likely significant, but policy developments are needed to
guide when and how accounting should be undertaken. Furthermore, ongoing research
is needed to create and enhance cost-effective accounting approaches.
PMID- 28413848
TI - Impact of data model and point density on aboveground forest biomass estimation
from airborne LiDAR.
AB - BACKGROUND: Accurate estimation of aboveground forest biomass (AGB) and its
dynamics is of paramount importance in understanding the role of forest in the
carbon cycle and the effective implementation of climate change mitigation
policies. LiDAR is currently the most accurate technology for AGB estimation.
LiDAR metrics can be derived from the 3D point cloud (echo-based) or from the
canopy height model (CHM). Different sensors and survey configurations can affect
the metrics derived from the LiDAR data. We evaluate the ability of the metrics
derived from the echo-based and CHM data models to estimate AGB in three
different biomes, as well as the impact of point density on the metrics derived
from them. RESULTS: Our results show that differences among metrics derived at
different point densities were significantly different from zero, with a larger
impact on CHM-based than echo-based metrics, particularly when the point density
was reduced to 1 point m-2. Both data models-echo-based and CHM-performed
similarly well in estimating AGB at the three study sites. For the temperate
forest in the Sierra Nevada Mountains, California, USA, R2 ranged from 0.79 to
0.8 and RMSE (relRMSE) from 69.69 (35.59%) to 70.71 (36.12%) Mg ha-1 for the echo
based model and from 0.76 to 0.78 and 73.84 (37.72%) to 128.20 (65.49%) Mg ha-1
for the CHM-based model. For the moist tropical forest on Barro Colorado Island,
Panama, the models gave R2 ranging between 0.70 and 0.71 and RMSE between 30.08
(12.36%) and 30.32 (12.46) Mg ha-1 [between 0.69-0.70 and 30.42 (12.50%) and
61.30 (25.19%) Mg ha-1] for the echo-based [CHM-based] models. Finally, for the
Atlantic forest in the Sierra do Mar, Brazil, R2 was between 0.58-0.69 and RMSE
between 37.73 (8.67%) and 39.77 (9.14%) Mg ha-1 for the echo-based model, whereas
for the CHM R2 was between 0.37-0.45 and RMSE between 45.43 (10.44%) and 67.23
(15.45%) Mg ha-1. CONCLUSIONS: Metrics derived from the CHM show a higher
dependence on point density than metrics derived from the echo-based data model.
Despite the median of the differences between metrics derived at different point
densities differing significantly from zero, the mean change was close to zero
and smaller than the standard deviation except for very low point densities (1
point m-2). The application of calibrated models to estimate AGB on metrics
derived from thinned datasets resulted in less than 5% error when metrics were
derived from the echo-based model. For CHM-based metrics, the same level of error
was obtained for point densities higher than 5 points m-2. The fact that reducing
point density does not introduce significant errors in AGB estimates is important
for biomass monitoring and for an effective implementation of climate change
mitigation policies such as REDD + due to its implications for the costs of data
acquisition. Both data models showed similar capability to estimate AGB when
point density was greater than or equal to 5 point m-2.
PMID- 28413849
TI - From berries to blocks: carbon stock quantification of a California vineyard.
AB - BACKGROUND: Quantifying terrestrial carbon (C) stocks in vineyards represents an
important opportunity for estimating C sequestration in perennial cropping
systems. Considering 7.2 M ha are dedicated to winegrape production globally, the
potential for annual C capture and storage in this crop is of interest to
mitigate greenhouse gas emissions. In this study, we used destructive sampling to
measure C stocks in the woody biomass of 15-year-old Cabernet Sauvignon vines
from a vineyard in California's northern San Joaquin Valley. We characterize C
stocks in terms of allometric variation between biomass fractions of roots,
aboveground wood, canes, leaves and fruits, and then test correlations between
easy-to-measure variables such as trunk diameter, pruning weights and harvest
weight to vine biomass fractions. Carbon stocks at the vineyard block scale were
validated from biomass mounds generated during vineyard removal. RESULTS: Total
vine C was estimated at 12.3 Mg C ha-1, of which 8.9 Mg C ha-1 came from
perennial vine biomass. Annual biomass was estimated at 1.7 Mg C ha-1 from leaves
and canes and 1.7 Mg C ha-1 from fruit. Strong, positive correlations were found
between the diameter of the trunk and overall woody C stocks (R2 = 0.85), pruning
weights and leaf and fruit C stocks (R2 = 0.93), and between fruit weight and
annual C stocks (R2 = 0.96). CONCLUSIONS: Vineyard C partitioning obtained in
this study provides detailed C storage estimations in order to understand the
spatial and temporal distribution of winegrape C. Allometric equations based on
simple and practical biomass and biometric measurements could enable winegrape
growers to more easily estimate existing and future C stocks by scaling up from
berries and vines to vineyard blocks.
PMID- 28413850
TI - Scenarios in tropical forest degradation: carbon stock trajectories for REDD.
AB - BACKGROUND: Human-caused disturbance to tropical rainforests-such as logging and
fire-causes substantial losses of carbon stocks. This is a critical issue to be
addressed in the context of policy discussions to implement REDD+. This work
reviews current scientific knowledge about the temporal dynamics of degradation
induced carbon emissions to describe common patterns of emissions from logging
and fire across tropical forest regions. Using best available information, we:
(i) develop short-term emissions factors (per area) for logging and fire
degradation scenarios in tropical forests; and (ii) describe the temporal pattern
of degradation emissions and recovery trajectory post logging and fire
disturbance. RESULTS: Average emissions from aboveground biomass were 19.9 MgC/ha
for logging and 46.0 MgC/ha for fire disturbance, with an average period of study
of 3.22 and 2.15 years post-disturbance, respectively. Longer-term studies of
post-logging forest recovery suggest that biomass accumulates to pre-disturbance
levels within a few decades. Very few studies exist on longer-term (>10 years)
effects of fire disturbance in tropical rainforests, and recovery patterns over
time are unknown. CONCLUSIONS: This review will aid in understanding whether
degradation emissions are a substantial component of country-level emissions
portfolios, or whether these emissions would be offset by forest recovery and
regeneration.
PMID- 28413851
TI - Detecting peatland drains with Object Based Image Analysis and Geoeye-1 imagery.
AB - BACKGROUND: Peatlands play an important role in the global carbon cycle. They
provide important ecosystem services including carbon sequestration and storage.
Drainage disturbs peatland ecosystem services. Mapping drains is difficult and
expensive and their spatial extent is, in many cases, unknown. An object based
image analysis (OBIA) was performed on a very high resolution satellite image
(Geoeye-1) to extract information about drain location and extent on a blanket
peatland in Ireland. Two accuracy assessment methods: Error matrix and the
completeness, correctness and quality (CCQ) were used to assess the extracted
data across the peatland and at several sub sites. The cost of the OBIA method
was compared with manual digitisation and field survey. The drain maps were also
used to assess the costs relating to blocking drains vs. a business-as-usual
scenario and estimating the impact of each on carbon fluxes at the study site.
RESULTS: The OBIA method performed well at almost all sites. Almost 500 km of
drains were detected within the peatland. In the error matrix method, overall
accuracy (OA) of detecting the drains was 94% and the kappa statistic was 0.66.
The OA for all sub-areas, except one, was 95-97%. The CCQ was 85%, 85% and 71%
respectively. The OBIA method was the most cost effective way to map peatland
drains and was at least 55% cheaper than either field survey or manual
digitisation, respectively. The extracted drain maps were used constrain the
study area CO2 flux which was 19% smaller than the prescribed Peatland Code value
for drained peatlands. CONCLUSIONS: The OBIA method used in this study showed
that it is possible to accurately extract maps of fine scale peatland drains over
large areas in a cost effective manner. The development of methods to map the
spatial extent of drains is important as they play a critical role in peatland
carbon dynamics. The objective of this study was to extract data on the spatial
extent of drains on a blanket bog in the west of Ireland. The results show that
information on drain extent and location can be extracted from high resolution
imagery and mapped with a high degree of accuracy. Under Article 3.4 of the Kyoto
Protocol Annex 1 parties can account for greenhouse gas emission by sources and
removals by sinks resulting from "wetlands drainage and rewetting". The ability
to map the spatial extent, density and location of peatlands drains means that
Annex 1 parties can develop strategies for drain blocking to aid reduction of CO2
emissions, DOC runoff and water discoloration. This paper highlights some
uncertainty around using one-size-fits-all emission factors for GHG in drained
peatlands and re-wetting scenarios. However, the OBIA method is robust and
accurate and could be used to assess the extent of drains in peatlands across the
globe aiding the refinement of peatland carbon dynamics .
PMID- 28413852
TI - Combining airborne laser scanning and Landsat data for statistical modeling of
soil carbon and tree biomass in Tanzanian Miombo woodlands.
AB - BACKGROUND: Soil carbon and biomass depletion can be used to identify and
quantify degraded soils, and by using remote sensing, there is potential to map
soil conditions over large areas. Landsat 8 Operational Land Imager satellite
data and airborne laser scanning data were evaluated separately and in
combination for modeling soil organic carbon, above ground tree biomass and below
ground tree biomass. The test site is situated in the Liwale district in
southeastern Tanzania and is dominated by Miombo woodlands. Tree data from 15 m
radius field-surveyed plots and samples of soil carbon down to a depth of 30 cm
were used as reference data for tree biomass and soil carbon estimations.
RESULTS: Cross-validated plot level error (RMSE) for predicting soil organic
carbon was 28% using only Landsat 8, 26% using laser only, and 23% for the
combination of the two. The plot level error for above ground tree biomass was
66% when using only Landsat 8, 50% for laser and 49% for the combination of
Landsat 8 and laser data. Results for below ground tree biomass were similar to
above ground biomass. Additionally it was found that an early dry season
satellite image was preferable for modelling biomass while images from later in
the dry season were better for modelling soil carbon. CONCLUSION: The results
show that laser data is superior to Landsat 8 when predicting both soil carbon
and biomass above and below ground in landscapes dominated by Miombo woodlands.
Furthermore, the combination of laser data and Landsat data were marginally
better than using laser data only.
PMID- 28413853
TI - Characterization of the gut microbiota in the golden takin (Budorcas taxicolor
bedfordi).
AB - The gut microbiota of mammals is a complex ecosystem, which is essential for
maintaining gut homeostasis and the host's health. The high throughput sequencing
allowed us to gain a deeper insight into the bacterial structure and diversity.
In order to improve the health status of the endangered golden takins, we first
characterized the fecal microbiota of healthy golden takins using high throughput
sequencing of the 16S rRNA genes V3-V4 hypervariable regions. Our results showed
that, Firstly, the gut microbiota community comprised 21 phyla, 40 classes, 62
orders, 96 families, and 216 genera. Firmicutes (67.59%) was the most abundant
phylum, followed by Bacteroidetes (23.57%) and Proteobacteria (2.37%). Secondly,
the golden takin maintained higher richness in spring than in the winter while
community diversity and evenness was not significantly different. Thirdly, four
female golden takins demonstrated highly similar microbiota and the five golden
takin males had relatively highly similar microbiota. All of our results might
indicate that the fecal microbiota of golden takins were influenced by the season
and the animal's sex. The findings provided theoretical basis regarding the gut
microbiota of golden takins and may offer new insights to protect this endangered
species.
PMID- 28413854
TI - Use of a pocket compression device for the prevention and treatment of pocket
hematoma after pacemaker and defibrillator implantation (STOP-HEMATOMA-I).
AB - BACKGROUND: Pocket hematoma is a recognized complication after placement of
cardiac implantable electronic devices and is associated with increased device
infection, length of hospitalization, and morbidity especially with uninterrupted
antiplatelet agents and anticoagulants. We assessed the use of a post-surgical
vest to decrease the incidence of pocket hematoma in patients undergoing device
implantation with uninterrupted antiplatelet and anticoagulants. METHODS: In this
observational study, a vest was used by 20 consecutive patients who were compared
to 20 age-, gender-, procedure-matched patients who received standard care. All
patients were continued on antiplatelet and anticoagulants in the perioperative
period. The pocket was assessed at post procedure day 0, 2, and 7, respectively.
RESULTS: There were no significant differences in the baseline characteristics
between both groups. Baseline mean international normalized ratio (INR) was
significantly higher in the vest group when compared with the control group (2.7
+/- 0.4 vs. 2.2 +/- 0.3 = <0.001). The incidence of pocket hematoma was
significantly lower in the vest group than the control group (0 vs 30%, p = 0.02)
at the end of 7 days. Control group had a total of six hematomas with one patient
requiring evacuation and blood transfusion. The vest group had three hematomas on
day 2 that resolved by day 7. CONCLUSIONS: The risk of moderate or large pocket
hematoma is significantly reduced with the use of this vest in high-risk patients
undergoing implantable devices on uninterrupted antiplatelet and anticoagulants.
PMID- 28413855
TI - Frequency of pacemaker malfunction associated with monopolar electrosurgery
during pulse generator replacement or upgrade surgery.
AB - PURPOSE: The aim of this study is to investigate the frequency of electrosurgery
related pacemaker malfunction. METHODS: A retrospective study was conducted to
investigate electrosurgery-related pacemaker malfunction in consecutive patients
undergoing pulse generator (PG) replacement or upgrade from two large hospitals
in Minneapolis, MN between January 2011 and January 2014. The occurrence of this
pacemaker malfunction was then studied by using MAUDE database for all four major
device vendors. RESULTS: A total of 1398 consecutive patients from 2 large
tertiary referral centers in Minneapolis, MN undergoing PG replacement or upgrade
surgery were retrospectively studied. Four patients (0.3% of all patients), all
with pacemakers from St Jude Medical (2.8%, 4 of 142) had output failure or
inappropriately low pacing rate below 30 bpm during electrosurgery, despite being
programmed in an asynchronous mode. During the same period, 1174 cases of
pacemaker malfunctions were reported on the same models in MAUDE database, 37 of
which (3.2%) were electrosurgery-related. Twenty-four cases (65%) had output
failure or inappropriate low pacing rate. The distribution of adverse events was
loss of pacing (59.5%), reversion to backup pacing (32.4%), inappropriate low
pacing rate (5.4%), and ventricular fibrillation (2.7%). The majority of these
(78.5%) occurred during PG replacement at ERI or upgrade surgery. No
electrosurgery-related malfunction was found in MAUDE database on 862 pacemaker
malfunction cases during the same period from other vendors. CONCLUSIONS:
Electrosurgery during PG replacement or upgrade surgery can trigger output
failure or inappropriate low pacing rate in certain models of modern pacemakers.
Cautions should be taken for pacemaker-dependent patients.
PMID- 28413856
TI - Erratum to: The Relationship Between Marijuana and Conventional Cigarette Smoking
Behavior from Early Adolescence to Adulthood.
PMID- 28413857
TI - A New Look at Genetic and Environmental Architecture on Lipids Using Non-Normal
Structural Equation Modeling in Male Twins: The NHLBI Twin Study.
AB - This study examined genetic and environmental influences on the lipid
concentrations of 1028 male twins using the novel univariate non-normal
structural equation modeling (nnSEM) ADCE and ACE models. In the best fitting
nnSEM ADCE model that was also better than the nnSEM ACE model, additive genetic
factors (A) explained 4%, dominant genetic factors (D) explained 17%, and common
(C) and unique (E) environmental factors explained 47% and 33% of the total
variance of high-density lipoprotein cholesterol (HDL-C). The percentage of
variation explained for other lipids was 0% (A), 30% (D), 34% (C) and 37% (E) for
low-density lipoprotein cholesterol (LDL-C); 30, 0, 31 and 39% for total
cholesterol; and 0, 31, 12 and 57% for triglycerides. It was concluded that
additive and dominant genetic factors simultaneously affected HDL-C
concentrations but not other lipids. Common and unique environmental factors
influenced concentrations of all lipids.
PMID- 28413858
TI - EPR Studies on the Properties of Model Photoreceptor Membranes Made of Natural
and Synthetic Lipids.
AB - The membranes of retina photoreceptors have unique lipid composition. They
contain a high concentration of polyunsaturated docosahexaenoic acid, with six
double bonds, and are enriched in phosphatidylethanolamines. Based on their
phospholipid composition and cholesterol content, membranes of photoreceptors can
be divided into three types: plasma membrane, young disks membranes, and old
disks membranes. High amount of docosahexaenoic acid, abundant illumination, and
high respiratory demands make these membranes sensitive to oxidative stress and
lipid peroxidation. Human retinas are not easily available for research,
therefore most research is done on bovine retinas. However, to follow, in a
controlled manner, the changes in membrane properties caused by different factors
it seems advisable to apply carefully prepared models of photoreceptor membranes.
Using synthetic lipids we prepared liposome models of three types of
photoreceptor membranes, and by means of electron paramagnetic resonance
spectroscopy and spin labeling technique we compared polarity and fluidity of
those model membranes with the properties of membranes consisting of natural
lipids extracted from photoreceptor outer segments of bovine retinas.
Additionally, we studied the effect of oxidation on the membrane properties in
the presence and in the absence of zeaxanthin, which is an antioxidant naturally
present in the human retina. The results show that there are significant
differences in polarity and fluidity between all investigated membranes, which
reflect differences in their lipid composition. The properties of the membranes
made of natural photoreceptor outer segment lipids are most similar to the ones
of the models of old disks membranes. Oxidation did not change the membrane
properties significantly; however, a slight ordering effect was observed in
liposomes made of natural photoreceptor outer segment lipids and in the model of
old disks membranes. Zeaxanthin affected polarity and fluidity mostly in the
model of old disks membranes. The results show that by careful selection and
appropriate proportions of lipid mixtures, it is possible to obtain synthetic
membranes of the properties similar to the natural ones.
PMID- 28413860
TI - Distribution and characterisation of CCK containing enteroendocrine cells of the
mouse small and large intestine.
AB - There is general consensus that enteroendocrine cells, EEC, containing the
enteric hormone cholecystokinin (CCK) are confined to the small intestine and
predominate in the duodenum and jejunum. Contrary to this, EEC that express the
gene for CCK have been isolated from the large intestine of the mouse and there
is evidence for EEC that contain CCK-like immunoreactivity in the mouse colon.
However, the human and rat colons do not contain CCK cells. In the current study,
we use immunohistochemistry to investigate CCK peptide presence in endocrine
cells, PCR to identify cck transcripts and chromatography to identify CCK peptide
forms in the mouse small and large intestine. The colocalisation of CCK and 5-HT,
hormones that have been hypothesised to derive from cells of different lineages,
was also investigated. CCK immunoreactivity was found in EEC throughout the mouse
small and large intestine but positive cells were rare in the rectum.
Immunoreactive EEC were as common in the caecum and proximal colon as they were
in the duodenum and jejunum. CCK gene transcripts were found in the mucosa
throughout the intestine but mRNA for gastrin, a hormone that can bind some anti
CCK antibodies, was only found in the stomach and duodenum. Characterisation of
CCK peptides of the colon by extraction, chromatographic separation and
radioimmunoassay revealed bioactive amidated and sulphated forms, including CCK-8
and CCK-33. Moreover, CCK-containing EEC in the large intestine bound antibodies
that target the biologically active sulfated form. Colocalisation of CCK and 5-HT
occurred in a proportion of EEC throughout the small intestine and in the caecum
but these hormones were not colocalised in the colon, where there was CCK and PYY
colocalisation. It is concluded that authentic, biologically active, CCK occurs
in EEC of the mouse large intestine.
PMID- 28413861
TI - Preconditioning with melatonin improves therapeutic outcomes of bone marrow
derived mesenchymal stem cells in targeting liver fibrosis induced by CCl4.
AB - Preconditioning of mesenchymal stem cells (MSCs) with melatonin (MT) has shown
promising results in animal models of myocardial infarction, renal ischemia and
cerebral ischemia. Here, we use this strategy in the liver fibrosis induced by
CCl4. There were five groups: normal, CCl4, CCl4 + vehicle, CCl4 + BMMSCs and
CCl4 + MT-bone marrow (BM)-derived MSCs (MT-BMMSCs). CCl4 was injected twice
weekly for 8 weeks and treatment either with cells or vehicle was performed at
the beginning of week 5 with a single dose. BMMSCs were preconditioned with MT
for 24 h before injection. MT-BMMSCs had a high ability of homing into the
injured liver (P <= 0.05 vs. BMMSCs). The CCl4 + MT-BMMSCs group showed higher
percentage of glycogen storage but lower percentage of collagen and lipid
accumulation (P <= 0.05 vs. CCl4 + BMMSCs). The CCl4 + MT-BMMSCs group showed
lower expressions of transforming growth factor-beta1 (TGF-beta1) and Bax and
lower content of sera alanine aminotransferase (ALT) but higher expressions of
matrix metalloproteinases (MMPs) and Bcl2 compared with the BMMSCs group (P <=
0.05). The results showed the better therapeutic outcomes of MT preconditioning
by probably improving cell homing and also better maintenance of the balance
between matrix degrading and accumulating factors.
PMID- 28413862
TI - A simple strategy for culturing morphologically-conserved rat hypothalamic
tanycytes.
AB - Hypothalamic tanycytes are specialized bipolar ependymal cells that line the
floor of the third ventricle. Given their strategic location, tanycytes are
believed to play several key functions including being a selective barrier and
controlling the amount of hypothalamic-derived factors reaching the anterior
pituitary. The in vitro culture of these cells has proved to be difficult. Here,
we report an improved method for the generation of primary cultures of rat
hypothalamic tanycytes. Ependymal cultures were derived from tissue dissected out
of the median eminence region of 10-day-old rats and cultured in a chemically
defined medium containing DMEM:F12, serum albumin, insulin, transferrin and the
antibiotic gentamycin. After 7 days in vitro, ~30% of the cultured cells
exhibited morphological features of tanycytes as observed by phase contrast or
scanning electron microscopy. Tanycyte-like cells were strongly immuno-reactive
for vimentin and dopamine-cAMP-regulated phospho-protein (DARPP-32) and weakly
immune-reactive for glial fibrillary acidic protein. Tanycyte-like cells
displayed a stable negative resting plasma membrane potential and failed to show
spiking properties in response to current injections. When exposed to fluorescent
beads in the culture medium, tanycyte-like cells exhibited a robust endocytosis.
Thus, the present method effectively yields cultures containing tanycyte-like
cells that resemble in vivo tanycytes in terms of morphologic features and
molecular markers as well as electrical and endocytic activity. To our knowledge,
this is the first protocol that allows the culturing of tanycyte-like cells that
can be individually identified and that conserve the morphology of tanycytes in
their natural physiological environment.
PMID- 28413859
TI - Meniscus, articular cartilage and nucleus pulposus: a comparative review of
cartilage-like tissues in anatomy, development and function.
AB - The degradation of cartilage in the human body is impacted by aging, disease,
genetic predisposition and continued insults resulting from daily activity. The
burden of cartilage defects (osteoarthritis, rheumatoid arthritis, intervertebral
disc damage, knee replacement surgeries, etc.) is daunting in light of
substantial economic and social stresses. This review strives to broaden the
scope of regenerative medicine and tissue engineering approaches used for
cartilage repair by comparing and contrasting the anatomical and functional
nature of the meniscus, articular cartilage (AC) and nucleus pulposus (NP). Many
review papers have provided detailed evaluations of these cartilages and
cartilage-like tissues individually but none have comprehensively examined the
parallels and inconsistencies in signaling, genetic expression and extracellular
matrix composition between tissues. For the first time, this review outlines the
importance of understanding these three tissues as unique entities, providing a
comparative analysis of anatomy, ultrastructure, biochemistry and function for
each tissue. This novel approach highlights the similarities and differences
between tissues, progressing research toward an understanding of what defines
each tissue as distinctive. The goal of this paper is to provide researchers with
the fundamental knowledge to correctly engineer the meniscus, AC and NP without
inadvertently developing the wrong tissue function or biochemistry.
PMID- 28413863
TI - Metabolism and homeostasis in the kidney: metabolic regulation through insulin
signaling in the kidney.
AB - Metabolic signaling pathways orchestrate the dynamic turnover between catabolic
and anabolic processes. Thereby, they ensure the viability of the cell and assure
proper function of the tissue in changing environments regarding the availability
of nutrients. Yet, renal cells are not considered to be prime targets of
metabolic signaling. Research of the last decade has proposed new roles of
specifically altered metabolic signaling pathways. In particular, the insulin
signaling cascade, a potent regulator of cellular metabolism and energy
homeostasis, seems to be implicated in the progression of diabetic and non
diabetic kidney disease. The aim of this review is to summarize the current
knowledge on metabolic signaling events in different renal compartments in states
of health and disease. We will focus on the role of insulin signaling events and
highlight recent advances in the understanding of the regulatory interplay
between insulin signaling and mitochondrial function contributing to the
pathogenesis of kidney disease.
PMID- 28413864
TI - Evaluation of Intracranial Microvessel Visualization in Mouse and Dog Models by
Using a New Rotating Cerium Anode X-ray System.
AB - OBJECTIVE: Lacunar stroke may be caused by infarction of small perforating
branches of the middle cerebral artery. We developed a microangiographic X-ray
system using a cerium anode to evaluate the perforating branches. METHODS: Iodine
has K-edges at 33.2 kilo electron volts. Cerium yields a characteristic X-ray of
34.6 kilo electron volts, therefore, the cerium anode X-ray system could detect
tiny amounts of contrast material. First, an X-ray chart was used to evaluate the
resolution. Second, the brains of mice were dissected and irradiated. Third, the
brains of dogs were excluded and irradiated. Fourth, iodine was perfused into the
carotid artery of living dogs during brain imaging. RESULTS: In the first
experiment, the cerium anode X-ray system elicited 4.86 clear line pairs. In
mice, the perforating branches of the middle cerebral artery could be visualized.
The perforating branches were clearly observed in dog brains ex situ even through
an acrylic plate, but not in conventional X-ray images. Iodine moving inside the
perforating branches was visualized in dog brains in situ using the cerium anode
X-ray system. CONCLUSION: The cerium anode X-ray system allowed us to visualize
the perforating branches of the middle cerebral artery in living dogs.
PMID- 28413865
TI - Protein-losing Enteropathy Caused by Spontaneous Reduction of Intussusception
with Meckel's Diverticulum.
AB - Protein-losing enteropathy (PLE) is a relatively rare condition. In this article,
we report the case of a 6-year-old boy diagnosed with PLE who developed
intussusception, in whom at operation Meckel's diverticulum was identified in his
intestine. Spontaneous reduction of intussusception is thought to relate to the
mechanism of PLE.
PMID- 28413866
TI - Inositol Hexakisphosphate Kinase 2 is a Presymptomatic Biomarker for Amyotrophic
Lateral Sclerosis.
AB - OBJECTIVE: Inositol hexakisphosphate kinase 2 (InsP6K2), an enzyme that converts
inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7),
induces cell death. InsP6K2 is abundant in the central nervous system, especially
anterior horn cells of spinal cord. To identify the role of InsP6K2 in
amyotrophic lateral sclerosis (ALS), we investigated the expression levels of
InsP6K2 in transgenic mice expressing mutant superoxide dismutase-1 (SOD1) (mSOD1
Tg mice). METHODS: The specimens of spinal cords were obtained from mSOD1 Tg mice
and age-matched wild-type mice. We investigated the expression of InsP6K2 at the
gene and protein levels of the spinal cord in mSOD1 Tg and wild-type mice.
RESULTS: The gene expression levels of InsP6K2 in mSOD1 Tg mice was significantly
higher than that in wild-type mice before ALS symptoms developed. In
immunohistochemistry and western blotting results showed that InsP6K2
translocated from the nucleus to the cytoplasm in mSOD1 Tg mice. CONCLUSION:
These findings suggest that InsP6K2 activates in mSOD1 Tg mice before the onset
of ALS. Therefore, InsP6K2 might be a presymptomatic biomarker for ALS.
PMID- 28413867
TI - A Study of Adjuvant Chemoradiotherapy with Tri-weekly Cisplatin for Postoperative
High-risk Oral Squamous Cell Carcinoma.
AB - OBJECTIVE: The aim of this study was to assess the feasibility and safety profile
of concurrent chemoradiotherapy with cisplatin in Japanese patients with
postoperative high-risk oral cancer. METHODS: Patients with high-risk
pathological features were selected from patients with oral squamous cell
carcinoma who underwent surgery at the Department of Oral and Maxillofacial
Surgery, Tokai University Hospital. Patients were given adjuvant
chemoradiotherapy with tri-weekly cisplatin (100 mg/m2) (66 Gy/33 Fr), and the
treatment completion rate was examined. RESULTS: A total of 27 patients were
enrolled between April 2011 and December 2012, including 19 males and 8 females.
The median follow-up period was 36 months, and the protocol completion rate was
81.5%. Grade 3 or higher adverse events included leukopenia in 16 patients
(59.3%), anemia in 7 patients (25.9%), mucositis in 2 patients (7.4%), increased
creatinine in 1 patient (3.7%), nausea in 4 patients (14.8%), and anorexia in 12
patients (44.4%). The 3-year overall survival rate was 66.7%, relapse-free
survival rate was 63.0%, and locoregional control rate was 77.8%. CONCLUSION: The
feasibility and safety profile of concurrent chemoradiotherapy with cisplatin in
Japanese patients with postoperative high-risk oral cancer were comparable to
pivotal phase III trials.
PMID- 28413868
TI - Goniosynechialysis and Repositioning of Intraocular Lens in a Case of Secondary
Angle Closure Glaucoma.
AB - PURPOSE: Implanting intraocular lens (IOL) in proper direction is important in
cataract surgery to reduce the possibility of undesirable complications. We
experienced a case who underwent vitrectomy combined with cataract surgery and
developed secondary angle closure glaucoma caused by IOL misdirection.
Goniosynechialysis (GSL) and repositioning of IOL successfully ameliorated the
high intraocular pressure (IOP). CASE REPORT: A 64-year-old male with massive
vitreous hemorrhage underwent vitrectomy combined with cataract surgery. In
implanting IOL, posterior capsule was accidentally raptured, and we were obliged
to implant IOL reversely in the ciliary sulcus. A month postoperatively, the
capture of IOL by iris and the shallow anterior chamber with iris bombe formation
led to the elevated IOP up to 60 mmHg. Laser iridotomy and maximum anti-glaucoma
medications including oral carbon anhydrase inhibitor could not control IOP.
Subsequently, we performed GSL and IOL repositioning to correct the lens
direction and the IOP was successfully reduced to normal level. CONCLUSION:
Reversely sulcus-implanted IOL should be repositioned to prevent secondary angle
closure glaucoma.
PMID- 28413869
TI - Salivary Duct Carcinoma with Invasive Micropapillary and Rhabdoid Feature Arising
in the Submandibular Gland.
AB - Salivary duct carcinoma (SDC) is a high-grade malignant salivary gland tumor
associated with poor prognosis, frequent recurrence, and metastasis. An 82-year
old man presented at the department of oral and maxillofacial surgery at Tokai
University Hospital with a painless swelling in the right submandibular region
that had been there for 20 years. On presentation, an elastic hard tumor, 50 * 50
mm in size, was observed in the submandibular region. Diagnostic imaging was
performed, and a malignant tumor in the submandibular gland was suspected. The
suspected tumor was excised and postoperative radiotherapy and adjuvant
chemotherapy were performed. Despite this treatment, the patient died of multiple
metastases 12 months postoperatively. SDCs are often diagnosed as carcinoma ex
pleomorphic adenomas and multiple variants and subtypes exist. This case was
histopathologically rare in terms of the coexistence of invasive micropapillary
and rhabdoid features.
PMID- 28413870
TI - Performance Evaluation of a Newly Developed and Fully Automated Bacteriological
Analyzer "RAISUS ANY" for Antimicrobial Susceptibility Testing of Fastidious
Bacteria Haemophilus influenzae and Streptococcus pneumoniae.
AB - OBJECTIVE: Antimicrobial susceptibility testing for fastidious bacteria, such as
Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S.
pneumoniae) has been performed manually. We evaluated the performance of a newly
developed fully automated system for rapid bacterial identification and
antimicrobial susceptibility testing "RAISUS ANY" (Nissui Pharmaceutical Co.,
Ltd.). METHODS: We evaluated the performance of "RAISUS ANY" for measurement of
minimal inhibitory concentrations (MICs) of H. influenzae and S. pneumoniae, in
comparison with the manual method (DP34, Eiken Chem. Co., Ltd.). The
repeatability of MICs was studied using the reference strain of these bacteria,
obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA).
RESULTS: The comparison with the manual method for 35 and 36 clinical strains of
H. influenzae and S. pneumonia showed 62.9-100% and 86.1-100% agreement,
respectively. Five of 35 H. influenzae strains that showed a trailing effect were
stably and accurately measured for MICs without a variation among the examiners.
CONCLUSION: In conclusion, the automated system "RAISUS ANY" provided a reliable
MICs data for H. influenzae and S. pneumonia, suggesting its improvement in
performance and reliability for routine antimicrobial susceptibility testing in
clinical bacteriological laboratories.
PMID- 28413871
TI - Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells
between Humans and a Humanized Xenograft Model.
AB - The aim of this study is to evaluate the feasibility of NOD/Shi-scid
IL2Rgammanull(NOG) mice transplanted with human CD34+/CD38-/Lin-/low
hematopoietic cells from cord blood (CB) as an experimental model of the gene
expression in human hematopoiesis. We compared the gene expressions of human
CD34+/CD38-/Lin-/low cells from human bone marrow (BM) and in xenograft models.
The microarray data revealed that 25 KEGG pathways were extracted from the
comparison of human CD34+/CD38-/Lin-/low HSCs between CB and BM, and that 17 of
them--which were mostly related to cellular survival, RNA metabolism and lymphoid
development--were shared with the xenograft model. When the probes that were
commonly altered in CD34+/CD38-/Lin-/low cells from both human and xenograft BM
were analyzed, most of them, including the genes related hypoxia, hematopoietic
differentiation, epigenetic modification, translation initiation, and RNA
degradation, were downregulated. These alterations of gene expression suggest a
reduced differentiation capacity and likely include key alterations of gene
expression for settlement of CB CD34+/CD38-/Lin-/low cells in BM. Our findings
demonstrate that the xenograft model of human CB CD34+/CD38-/Lin-/low cells using
NOG mice was useful, at least in part, for the evaluation of the gene expression
profile of human hematopoietic stem cells.
PMID- 28413872
TI - Favorable Effect on Blood Volume Control in Hemodialysis Patients with Type 2
Diabetes after Switching from Insulin Therapy to Liraglutide, a Human Glucagon
like Peptide-1 Analog--Results from a Pilot Study in Japan-.
AB - OBJECTIVE: Hemodialysis patients are advised to limit the intake of foods in
order to control volume status and body weight (BW). We report the clinical
course of five Japanese hemodialysis patients with type 2 diabetes mellitus
(T2DM) who were switched from insulin to liraglutide, and the efficacy of the
treatment, especially in terms of changes in interdialysis weight gain (IDWG).
METHODS: This retrospective pilot study included 5 Japanese hemodialysis patients
with T2DM. Insulin and other oral hypoglycemic agents, if any, were discontinued
before switching to liraglutide. The initial dose of liraglutide was set at 0.3
mg/day for more than 1 week, increased to 0.6 mg/day for more than 1 week and
then, to 0.9 mg/day if needed. RESULTS: At baseline, the mean body mass index
(BMI) was 23.2 +/- 1.2 kg/m2 and mean IDWG was 2.0 +/- 0.4 kg. The required dose
of liraglutide ranged from 0.3 to 0.9 mg/day. At the end of 3-month treatment,
liraglutide reduced HbA1c level, BMI, and IDWG. A significant decrease in
cardiothoracic ratio was confirmed on chest radiography. CONCLUSION: Switching
from insulin to liraglutide seems effective in hemodialysis patients with T2DM,
especially in those with difficult blood fluid volume control associated with
failure of dietary restriction.
PMID- 28413874
TI - Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR
AC): summary of conclusions and recommendations, 1-2 February 2017 meeting.
PMID- 28413873
TI - The Apparent Diffusion Coefficient (ADC) as a Potential Marker of Inflammation
Associated with Body Abscesses.
AB - OBJECTIVE: To assess the feasibility of apparent diffusion coefficient analysis
in evaluating the inflammatory severity of extracranial abscesses. METHODS: This
retrospective study included 23 patients with solitary body abscesses (except
those in the brain) who underwent 1.5-T diffusion-weighted magnetic resonance
imaging (DWI) at b-values of 0 and 1000 s/mm2. Three types of the Apparent
Diffusion Coefficient (ADC) measurements of abscesses were performed: the mean
ADC value in region of interest (ROI), volume of interest (VOI), and histogram
analysis of the ADC distribution in the VOI. Furthermore, two different areas
were used: high-intensity area on b = 0 and b = 1000 s/mm2 images. Subsequently,
correlations between ADC data and C-reactive protein (CRP) levels were assessed
using Pearson's correlation coefficient (R) analyses. RESULTS: The strongest
correlation was observed between the mean ADC value in VOI and CRP level (R =
0.78, P < 0.01), followed by ROI (R = 0.77, P < 0.01) by using the high-intensity
area on the b = 0 s/mm2 images. CONCLUSION: The mean ADC value in the ROI
encompassing the abscess at a b-value of 0 s/mm2 may be useful to assess the
inflammatory activity of an abscess in daily practice.
PMID- 28413875
TI - Zika virus: an epidemiological update.
PMID- 28413876
TI - Generation of an Orthogonal Protein-Protein Interface with a Noncanonical Amino
Acid.
AB - We have engineered the protein interface of the Escherichia coli chorismate
mutase (EcCM) homodimer to be dependent on incorporation of a noncanonical amino
acid (ncAA) at residue 72. The large hydrophobic amino acid p-benzoyl
phenylalanine (pBzF) was substituted for Tyr72, which led to a catalytically
inactive protein. A library of five residues (Leu25', Arg29', Leu76, Ile80' and
Asp83') surrounding pBzF72 was generated and subjected to a growth based
selection in a chorismate mutase deficient strain. An EcCM variant (Phe25',
pBzF72, Thr76, Gly80' and Tyr83') forms a stable homodimer, has catalytic
activity similar to the wild type enzyme, and unfolds with a Tm of 53 degrees C.
The X-ray crystal structure reveals a pi-pi stacking and hydrogen bonding
interactions that stabilize the new protein interface. The strategy described
here should be useful for generating organisms that are dependent on the presence
of a ncAA for growth.
PMID- 28413877
TI - Correction to Reduction Sensitive Lipid Conjugates of Tenofovir: Synthesis,
Stability, and Antiviral Activity.
PMID- 28413878
TI - An Efficient Method Based on Lattice Construction and the Genetic Algorithm for
Optimization of Large Lennard-Jones Clusters.
AB - Geometric methods for the construction of three structural motifs, the
icosahedron, Ino's decahedron, and the complete octahedron, are proposed. On the
basis of the constructed lattices and the genetic algorithm, a method for
optimization of large size Lennard-Jones (LJ) clusters is presented. Initially,
the proposed method is validated by optimization of LJ13-309 clusters with the
above structural motifs. Results show that the proposed method successfully
located all the lowest known minima with an excellent performance; for example,
based on Ino's decahedron with 147 lattice sites, the mean time consumed for
successful optimization of LJ75 is only 0.61 s (Pentium III, 1 GHz), and the
percentage success is 100%. Then, putative global minima of LJ310-561 clusters
are predicted with the method. By theoretical analysis, these global minima are
reasonable, although further verification or proof is still needed.
PMID- 28413879
TI - Structural Distribution of Lennard-Jones Clusters Containing 562 to 1000 Atoms.
AB - On the basis of the icosahedral and decahedral lattices, the lowest energies of
the Lennard-Jones (LJ) clusters containing 562-1000 atoms with the two motifs are
obtained by using a greedy search method (GSM). Energy comparison between the
decahedra and icosahedra shows that icosahedral structures are predominant.
However, most of the icosahedral structures with the central vacancy are more
stable than that without the central vacancy. On the other hand, in the range of
562-1000 atoms, there are 41 LJ clusters with the decahedral motif. The number of
decahedra increases remarkably compared with the smaller LJ clusters.
Consequently, the magic numbers and growth characters of decahedral clusters are
also studied, and the results show that the magic numbers of intermediate
decahedral clusters occur at 654, 755, 807, 843, 879, 915, and 935.
PMID- 28413880
TI - Syntheses of Gliocladin C and Related Alkaloids.
AB - A unique approach to gliocladin C and related alkaloids was developed that
features an unprecedented nucleophilic addition of a diketopiperazine to an
isatin derivative followed by a Friedel-Crafts alkylation of the resultant
tertiary alcohol with indole to set the key quaternary center. Chemoselective
oxindole reduction and cyclization delivered a pivotal hexahydropyrrolo[2,3
b]indole diketopiperazine intermediate that was readily converted into (+/-)
gliocladin C, (+/-)-T988C, and (+/-)-gliocladine C, culminating in the shortest
approach to these alkaloids reported to date.
PMID- 28413881
TI - Molecular Mechanism of Stabilizing the Helical Structure of Huntingtin N17 in a
Micellar Environment.
AB - Huntington's disease is a deadly neurodegenerative disease caused by the
fibrilization of huntingtin (HTT) exon-1 protein mutants. Despite extensive
efforts over the past decade, much remains unknown about the structures of
(mutant) HTT exon-1 and their enigmatic roles in aggregation. Particularly,
whether the first 17 residues in the N-terminal (HTT-N17) adopt a helical or a
coiled structure remains unclear. Here, with the rigorous study of molecular
dynamics simulations, we explored the most possible structures of HTT-N17 in both
dodecylphosphocholine (DPC) micelles and aqueous solution, using three commonly
applied force fields (OPLS-AA/L, CHARMM36, and AMBER99sb*-ILDNP) to examine the
underlying molecular mechanisms and rule out potential artifacts. We show that
local environments are essential for determining the secondary structure of HTT
N17. This is evidenced by the insertion of five hydrophobic residues of HTT-N17
into the DPC micelle, which promotes the formation of an amphipathic helix,
whereas such amphipathic helices unfold quickly in aqueous solution. A relatively
low free-energy barrier (~3 kcal/mol) for the secondary structure transformation
was also observed for all three force fields from their respective folding-free
energy landscapes, which accounts for possible HTT-N17 conformational changes
upon environmental shifts such as membrane binding and protein complex
aggregation.
PMID- 28413882
TI - Consequences of Surface Oxophilicity of Ni, Ni-Co, and Co Clusters on Methane
Activation.
AB - This study describes a new C-H bond activation pathway during CH4-CO2 reactions
on oxophilic Ni-Co and Co clusters, unlike those established previously on Ni
clusters. The initial C-H bond activation remains as the sole kinetically
relevant step on Ni-Co, Ni, and Co clusters, but their specific reaction paths
vary. On Ni clusters, C-H bond activation occurs via an oxidative addition step
that involves a three-center (H3C...*...H)? transition state, during which a Ni
atom inserts into the C-H bond and donates its electron density into the C-H
bond's antibonding orbital. Ni-Co clusters are more oxophilic than Ni; thus,
their surfaces are covered with oxygen adatoms. An oxygen adatom and a vicinal Co
atom form a metal-oxygen site-pair that cleaves the C-H bond via a sigma bond
metathesis reaction, during which the Co inserts into the C-H bond while the
oxygen abstracts the leaving H-atom in a concerted, four-center
(H3C...*...H...O*)? transition state. Similarly, Co clusters also catalyze the
sigma bond metathesis step, but much less effectively because of their higher
oxophilicities, much stronger binding to oxygen, and less effective hydrogen
abstraction than Ni-Co clusters. On Ni-Co and Co clusters, the pseudo-first-order
rate coefficients are single-valued functions of the CO2-to-CO ratio (or H2O-to
H2 ratio), because this ratio prescribes the oxygen chemical potentials and the
relative abundances of metal-oxygen site-pairs through the water-gas shift
equilibrium. The direct involvement of reactive oxygen in the kinetically
relevant step leads to more effective CH4 turnovers and complete elimination of
coke deposition on Ni-Co bimetallic clusters.
PMID- 28413883
TI - Comment: The Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological
Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.
PMID- 28413884
TI - Incidence and Risk Factors of Venous Thromboembolism After Orthopaedic Foot and
Ankle Surgery.
AB - BACKGROUND: This study examines the incidence and risk of postoperative
symptomatic venous thromboembolism (VTE) after orthopaedic foot/ankle surgery.
MATERIALS: Patients that received foot/ankle surgery between 2006 and 2016 were
reviewed. Inclusion criteria were surgical patients that were without
coagulopathy, previous VTE, and/or using anticoagulation medications including
aspirin. Age, sex, body mass index, medical comorbidities, and surgical diagnosis
and procedure(s) were noted. Records were reviewed to see who developed a
symptomatic VTE within 90 days from surgery. RESULTS: This study involved 2774
patients that received foot/ankle surgery between 2006 and 2016. Of them, 22
(0.79%) developed a VTE within 90 days from surgery. The mean age of these
patients was 49.5 years. Twelve patients were male and 10 were female. Sixteen
patients were obese and 6 were nonobese. Postoperative VTEs were 14
infrapopliteal deep vein thrombosis (DVT), 1 suprapopliteal DVT, and 7 pulmonary
emboli. The most common surgeries involved were ankle fracture repair in 8
(0.29%), Achilles tendon repair in 2 (0.07%), ankle ligament reconstruction in 2,
and hammer-toe correction in 2 patients. Obesity was predictive of a
postoperative VTE to a statistically significant degree (P = .04). Age, sex,
medical comorbidities, diagnosis, and type of surgery were not significantly
prognostic for a postsurgical VTE (P >= .05). DISCUSSION: The incidence of VTE
after foot/ankle surgery is low. However, obese patients are at significantly
higher risk for VTE after such procedures. CLINICAL RELEVANCE: These findings are
important when educating patients as to their risks of developing a VTE after
orthopaedic foot/ankle surgery. LEVELS OF EVIDENCE: Level III: Retrospective
cohort study.
PMID- 28413885
TI - Understanding Latino Grandparents Raising Grandchildren Through a Bioecological
Lens.
AB - The purpose of this article is to provide a summary of the published research
addressing the challenges and strengths of Latino grandparents raising
grandchildren in the United States. Using the bioecological framework as a guide
to organize and understand the published literature addressing Latino grandparent
caregivers, we examined refereed articles published over the past 19 years. This
framework provides a lens for understanding and situating research on Latino
grandparents raising grandchildren to discover Latino grandparents' strengths and
challenges. The areas of foci include financial challenges, intergenerational
relationships, reasons for caregiving, health status, language barriers, and
culture. This article concludes with future research opportunities and a call to
action for more research on Latino grandparents raising grandchildren.
PMID- 28413886
TI - Effects of cadmium on Bcl-2/ Bax expression ratio in rat cortex brain and
hippocampus.
AB - To investigate the underlying mechanism of neurotoxicity of cadmium, we examined
the effects of intraperitoneal injection of cadmium on messenger RNA (mRNA)
expression of Bcl-2 (B-cell lymphoma 2) and Bax (Bcl2-associated x) genes and
caspase-3/7 activation in rat hippocampus and frontal cortex. Twenty-eight male
Wistar rats weighing 200-250 g were randomly divided into four groups. Control
group received saline and three other groups received cadmium at doses of 1, 2
and 4 mg/kg (body weight) for 15 successive days. One day after the last
injection, the hippocampus and frontal cortex were dissected and removed and then
the expression of Bcl-2 and Bax genes was evaluated using real-time polymerase
chain reaction and apoptotic studies was done using caspase-3/7 activation assay.
Cadmium reduced the mRNA level of Bcl-2 in the control group at doses of 1 ( p <
0.01), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus and cortex cells. The mRNA
level of Bax increased significantly compared to the control group at the doses
of 1 ( p < 0.05), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus. The mRNA level
of Bax was increased significantly compared to the control group at the doses of
2 and 4 mg/kg ( p < 0.001) in rat cortex cells. Cadmium increased caspase-3/7
activity at doses of 1, 2 and 4 mg/kg in rat hippocampus. Caspase-3/7 activity
was increased significantly at dose of 4 mg/kg in rat cortex. This decreased Bcl
2/Bax mRNA ratio induces cell apoptosis. Apoptotic effect of cadmium may be
through the mitochondrial pathway by the activation of caspase-3/7.
PMID- 28413887
TI - Decline in sperm count in European men during the past 50 years.
AB - PURPOSE: To investigate whether the sperm concentration of European men is
deteriorating over the past 50 years of time. MATERIALS AND METHODS: We analysed
the data published in English language articles in the past 50 years in altering
sperm concentration in European men. RESULTS: A time-dependent decline of sperm
concentration ( r = -0.307, p = 0.02) in the last 50 years and an overall 32.5%
decrease in mean sperm concentration was noted. CONCLUSION: This comprehensive,
evidence-based meta-analysis concisely presents the evidence of decreased sperm
concentration in European male over the past 50 years to serve the scientific
research zone related to male reproductive health.
PMID- 28413888
TI - Implementation and evaluation of a Danish test battery for auditory processing
disorder in children.
AB - OBJECTIVE: This study presents a Danish test battery for auditory processing
disorder (APD). The tests were evaluated as to normative cut-off values (pass
fail criteria) and their test-retest reliability. DESIGN: The battery consists of
four behavioural tests: the filtered words (FW) test, the dichotic digits (DD)
test, the gap detection (GD) test and the binaural masking level difference
(BMLD) test. The tests were evaluated through listening experiments on children
with no known history of auditory problems. STUDY SAMPLE: The normative cut-off
values were obtained from 158 children (75 boys and 83 girls, aged 6-16 years),
whereas the test-retest reliability was obtained from 20 children (10 boys and 10
girls, aged 6-11 years). RESULTS: For each of the four tests one to four
different cut-off values were determined depending on whether the scores from the
two ears and the different age groups could be pooled. For each of the four tests
the test-retest reliability was found to be satisfactory. The test-retest
reliability was highest for the FW and the DD test. CONCLUSIONS: A Danish APD
test battery is now available for clinical use with normative data.
PMID- 28413889
TI - Shedding light into the black box: A prospective longitudinal study identifying
the CanMEDS roles of final year medical students' on-ward activities.
AB - INTRODUCTION: To our best knowledge, a rigorous prospective analysis of final
year medical students' (FY medical students) activity profiles during workplace
learning is lacking. The present study investigated the CanMEDS characteristics
of all on-ward activities performed by internal medicine FY medical students. We
tested the hypotheses that during FY medical student workplace training (I)
routine activities are predominantly performed, while supervised, more complex
activities are underrepresented with (II) FY medical students performing an
insufficient number of autonomous activities and that (III) the CanMEDS roles of
the Communicator and the Professional prevail. METHODS: During the second and the
sixth week of their final year trimester at the University of Heidelberg Medical
Hospital, N = 34 FY medical students (73% female; mean age 26.4 +/- 2.4) were
asked to keep a detailed record of all their on-ward activities and to document
the duration, mode of action (active versus passive; independent versus
supervised), estimated relevance for later practice, and difficulty-level in
specially designed activity logbooks. CanMEDS roles were assigned to the
documented activities via post-hoc expert consensus. RESULTS: About 4308
activities lasting a total of 2211.4 h were documented. Drawing blood (20.8%) was
the most frequently documented medical activity followed by full admission
procedures (9.6%). About 14.9% of the time was spent with non-medical activities.
About 82.1% of all medical activities performed went unsupervised. The
Communicator (42%), the Professional (38%), and the Collaborator (7%) were
assigned as the top three CanMEDS roles. CONCLUSIONS: The results call for
increased efforts in creating more authentic learning experiences for FY medical
students shifting towards more complex, supervised tasks, and improved team
integration.
PMID- 28413890
TI - Design, synthesis, and evaluation of novel 2-phenylpropionic acid derivatives as
dual COX inhibitory-antibacterial agents.
PMID- 28413891
TI - Safety of peripherally inserted central catheters during pregnancy: a
retrospective study.
AB - PURPOSE: We investigated the incidence of complications associated with
peripherally inserted central line catheters, inserted using a standardized
technique, during pregnancy and the postpartum period. MATERIALS AND METHODS: A
retrospective case series was performed that included all pregnant and postpartum
women who received peripherally inserted central catheters (PICCs) at a single
institution between 2006 and 2014. Patient demographics and data on infectious,
mechanical and thrombotic complications were collected. Some patients required
more than one line insertion during the same pregnancy. In these instances, only
the first line placement for each subject was included in the analysis of
complications. RESULTS: One hundred and forty-six catheters were inserted in 112
pregnant and postpartum patients. The total incidence of complications was 17%
(19/112). Specific complications included infection (n = 4, 3.6%), mechanical (n
= 5, 4.4%), deep venous thrombosis (n = 2, 1.8%) and other (n = 8, 7.1%).
Demographics of the complication and no complication groups were similar.
CONCLUSIONS: In contrast with previous studies, we report a complication rate
associated with peripheral line use in pregnant and postpartum women that appears
similar to that in non-pregnant populations.
PMID- 28413892
TI - Amyloid detection in the transverse carpal ligament of patients with hereditary
ATTR V30M amyloidosis and carpal tunnel syndrome.
AB - INTRODUCTION: Carpal tunnel syndrome (CTS) is a nonspecific manifestation of
hereditary ATTR amyloidosis (ATTRm). Amyloid deposition of wild-type TTR (WT
ATTR) has been found in transverse carpal ligament (TCL) in idiopathic CTS. We
retrospectively studied a group of patients with ATTRm and CTS submitted to
carpal tunnel release surgery (CTRS). METHODS: From the nerve conduction studies
performed in our Clinical Unit dedicated to hereditary amyloidosis between July
2009 and October 2013, we selected patients who fulfilled neurophysiological
criteria for CTS, had been submitted to CTRS and whose TCL was available for
pathology. Clinical registries were reviewed and amyloid detection in the
ligaments was performed using Congo-red staining. RESULTS: We included 16
patients: three males (18.8%), mean age = 46.1 years old, all with V30M mutation.
At the time of surgery, four patients were considered asymptomatic and 12
symptomatic carriers, five of them late-onset ATTRm (onset age >50 years old). In
all but one patient, the CTS preceded the polyneuropathy. Amyloid detection in
the TCL was positive in 14 patients (87.5%). DISCUSSION/CONCLUSIONS: In most
patients, CTS preceded or was contemporary to the polyneuropathy and amyloid
detection in TCL was positive. The detection of amyloid in TCL may add
specificity to CTS as an early manifestation of the disease but more studies are
needed.
PMID- 28413893
TI - The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin
Cutoff Points in Double Heterozygous Hb E/- -SEA alpha-Thalassemia-1 Carriers are
Dependent on Hemoglobin Levels.
AB - Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- -SEA (Southeast
Asian) (alpha-thalassemia-1) (alpha-thal-1) in patients first diagnosed as
carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular
volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed
in this double heterozygosity. However, the cutoff points of these parameters
have never been systematically established. Here, we analyzed Hb E and red blood
cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of
- -SEA and -alpha3.7 (alpha-thal-2; rightward) deletions, to establish the cutoff
points. Then, the established cutoff points were evaluated in 184 Hb E patients.
It was found that the cutoff points of Hb E, MCV, MCH were significantly
dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff
points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and
were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0
11.9 g/dL. Finally, in the group having Hb levels >=12.0 g/dL, the cutoff points
of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to
screen for the double heterozygous Hb E/- -SEA anomaly in patients initially
diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing
the suitable cutoff points of these three parameters.
PMID- 28413894
TI - Isolated Gastrocnemius Recession for the Treatment of Achilles Tendinopathy.
AB - BACKGROUND: Various treatment modalities have been described for Achilles
tendinopathy with varying degrees of success. The rationale for the gastrocnemius
recession procedure is to decrease the mechanical overload of the Achilles tendon
arising from an equinus contracture. METHODS: We retrospectively reviewed 25
patients who underwent an isolated gastrocnemius recession procedure at our
institution between May 2013 and April 2015 by a single surgeon. Clinical outcome
was evaluated on the basis of pain, utilizing visual analog scale (VAS) scores
and the Foot Function Index (FFI) by telephonic interview. Student's t test and
one-way analysis of variance were used for statistical analysis. RESULTS: The
average age of patients was 53.2 years with an average body mass index of 35.8
kg/m2. The average follow-up was 13.1 months. All 25 patients had a decrease in
VAS scores from an average of 8.9 preoperatively to 2.0 at the 6-week visit. The
average FFI went from 73.5 preoperatively to 27.4 at final follow-up. Two out of
25 patients had a postoperative sural neuritis with a total complication rate of
12%. Twenty-one of 25 patients (84%) reported total or significant pain relief.
CONCLUSION: The medium-term results of our study suggest that an isolated
gastrocnemius recession is a simple, effective, and safe surgical procedure for
the treatment of Achilles tendinopathy. LEVELS OF EVIDENCE: Therapeutic, Level
IV: Retrospective.
PMID- 28413895
TI - Response to restrictive lung disease: low EPAP - good ventilation. Is it real?
PMID- 28413896
TI - Congenital malformations, palliative care and postnatal redirection to more
intensive treatment - a review at a Swiss tertiary center.
AB - PURPOSE: The so-called lethal malformations pose ethical challenges. Most
affected fetuses die before or at birth. Live-born neonates commonly receive
palliative care. If the postnatal course is better than expected, redirection
towards more treatment may occur. We aimed to analyze this in a Swiss patient
cohort. MATERIALS AND METHODS: Over 6 years, fetal malformation was suspected in
1113 cases. We identified patients prenatally assigned to palliative care,
assessed pre- and postnatal diagnoses, and outcomes. RESULTS: Fourteen neonates
received palliative care. Eleven patients received palliative care following late
termination of pregnancy, for three, palliative care was planned and the fetus
died during delivery, for two, the outcome was unknown (incomplete
documentation). Genetic testing was performed in 50%. The predominant diagnostic
group was central nervous system malformations (33%), followed by chromosomal
aberrations (20%) and renal anomalies (17%). One child assigned to palliative
care was resuscitated. Antenatal findings were anhydramnios and pulmonary
hypoplasia. Postnatally, respiration was better than expected. The neonate was
admitted to intensive care, died on day one. CONCLUSIONS: Nervous system
malformations seem to be a major criterion for foregoing life-sustaining
interventions. Redirection towards more treatment is rare. This may reflect
precise prenatal prognostication; a degree of self-fulfilling prophecy cannot be
excluded.
PMID- 28413897
TI - Fibroadenoma With Pleomorphic Stromal Giant Cells: It's Not as Bad as It Looks!
AB - Clinically relevant histological categorization of fibroepithelial lesions can be
a daunting task, especially in a core needle biopsy. Assessment of stromal
nuclear atypia, including nuclear pleomorphism and mitotic activity, is a key
morphological feature employed to classify fibroepithelial lesions. We describe a
case of fibroadenoma with markedly atypical nuclear features in the stromal cells
that led to misclassification as phyllodes tumor in the core needle biopsy.
Excision showed a fibroadenoma containing pleomorphic stromal giant cells, with
occasional mitotic figures, including atypical forms. Aforementioned nuclear
findings in a fibroepithelial lesion raise a legitimate question of phyllodes
tumor. Knowledge of this pitfall may help avoid overtreatment of an otherwise
benign fibroepithelial lesion.
PMID- 28413898
TI - ERP correlates of attentional processing in spider fear: evidence of threat
specific hypervigilance.
AB - Attentional bias towards threat can be demonstrated by enhanced processing of
threat-related targets and/or greater interference when threat-related
distractors are present. These effects are argued to reflect processing within
the orienting and executive control networks of the brain respectively. This
study investigated behavioural (RT) and electrophysiological correlates of early
selective attention and top-down attentional control among females with high (n =
16) or low (n = 16) spider fear (Mean age = 22 years). Participants completed a
novel flanker go/nogo task in which a central schematic flower or spider stimulus
was flanked by either congruent or incongruent distractors. Participants
responded to green stimuli (go trials) and withheld response to yellow stimuli
(nogo trials). High fear participants demonstrated significantly shorter reaction
times and greater P1 amplitude to spider targets, suggesting specific
hypervigilance towards threat-relevant stimuli. In contrast to predictions, there
was little evidence for behavioural interference effects or differences in N2
amplitude when distractor stimuli were threat-relevant.
PMID- 28413899
TI - Changes in the oxidative stress/anti-oxidant system after exposure to sulfur
mustard and antioxidant strategies in the therapy, a review.
AB - Sulfur mustard, in a chemical name bis(2-chloroethyl) sulfide, is a chemical
warfare agent. It is cytotoxic and blister forming once spread over the skin.
Though exact molecular mechanism of sulfur mustard toxic action remains unknown,
inflammation and oxidative stress development are considered as the most relevant
pathological consequences. Applications of either low-molecular weight
antioxidants or cofactors for enzymatic antioxidants are considered as suitable
ways how to ameliorate the poisoning. In this article, survey of literature on
countermeasures against sulfur mustard poisoning are given and evidence of
oxidative stress role during sulfur mustard poisoning and availability of
antioxidants for the therapy are discussed.
PMID- 28413900
TI - Efficacy of Cognitive Behavioral Therapy With and Without Medication for Adults
With ADHD.
AB - OBJECTIVE: Recent trials have demonstrated efficacy of cognitive behavioral
therapy (CBT) in medicated adults with ADHD. Efficacy of CBT in unmedicated
versus medicated adults remains mostly unknown. We evaluated the effects of group
CBT alone versus combined with medication on ADHD symptoms and functional
outcomes in adult patients. METHOD: Eighty-eight adults with ADHD received 12
manualized group CBT sessions, accompanied by individual coaching, either without
( n = 46) or with ( n = 42) medication. Treatment effects were evaluated
following treatment and 3-month and 6-month follow-up using un-blinded self
report and observer ratings. RESULTS: CBT + medication resulted in greater
improvements than CBT alone in ADHD symptoms, organizational skills, and self
esteem. Group differences diminished over follow-up, as the CBT alone group
continued improving, while the combined group maintained the gains. CONCLUSION:
CBT + medication outperformed CBT alone for ADHD symptoms, organizational skills,
and self-esteem, although its superiority tended to decrease over follow-up.
PMID- 28413902
TI - Sustainable development goals and road traffic injuries: the new research
challenge.
PMID- 28413901
TI - Elevation of CD16+CD56+ NK-cells and down-regulation of serum interleukin-21 (IL
21) and IL-1alpha after splenectomy in relapsed hemophagocytic
lymphohistiocytosis of unknown cause.
AB - OBJECTIVES: Encouraging progress has been made in application of splenectomy in
the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown
cause. The aim was to determine the roles of lymphocyte subpopulations and
inflammatory cytokines in splenectomy. METHODS: We retrospectively analyzed
changes in lymphocyte subpopulations and levels of inflammatory cytokines at
different time-points before and after splenectomy in the patients with relapsed
HLH of unknown cause, as well as the correlations between these changes and the
disease prognosis. RESULTS: During the period from June 2006 to June 2016, we
enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated
with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based
on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were
available for analysis. Results showed a significant increase in both percentage
of CD16+CD56+ NK cells (P = 0.003) and NK cell activity (P = 0.028) at 24 wk
after splenectomy compared to their baseline pre-surgery levels. We also examined
seven patients for the changes in cytokine levels before and after splenectomy
and found that IL-21 and IL-1alpha decreased at 4 wk after splenectomy (P <
0.05). Seven non-lymphoma patients determined as no response to treatment (NR)
prior to splenectomy had significantly longer survival (P = 0.001) compared to
the 24 patients with relapsed HLH of unknown cause who were also determined as NR
but not treated by splenectomy. DISCUSSION: Splenectomy can improve clinical
symptoms and survival of patients with relapsed HLH of unknown cause. The
mechanism is likely related to the changes in percent NK cells and cytokines (IL
21 and IL-1alpha) after surgery.
PMID- 28413903
TI - Digital revascularization and replantation using the wide-awake hand surgery
technique.
AB - : The use of local anaesthesia and adrenaline for hand surgery is gaining
popularity; however, where vascularity is impaired, wide-awake surgery is
considered a contraindication. We present our case series of five digital
devascularizations and eight amputations that underwent surgery using the 'wide
awake' anaesthetic technique. A temporary digital tourniquet (< 20 min) was used
in three cases to identify structures quickly. The anastomoses were performed
under local anaesthesia without a tourniquet. All cases had successful re
establishment of blood flow with good perfusion to the digital tips; no cases
were re-explored because of vascular crisis. Four cases had minor superficial
soft tissue necrosis that healed secondarily. We conclude that digital
revascularization and replantation can be performed under local anaesthesia with
use of adrenaline and without detriment to the traumatized digit provided careful
patient selection and adequate operator experience are available. LEVEL OF
EVIDENCE: IV.
PMID- 28413904
TI - Helicobacter Pylori Infection in Texas Hispanic and Non-Hispanic White Men:
Implications for Gastric Cancer Risk Disparities.
AB - Chronic Helicobacter pylori ( H. pylori) infection is a major gastric
adenocarcinoma (GA) risk factor. GA disproportionately affects U.S. Hispanics
compared with non-Hispanic Whites (NHWs). Since H. pylori infection studies in
Hispanics are few, infection rates in Hispanic and NHW men in Bexar County were
compared, and relationships with ethnicity and obesity examined. Age- and zip
code-matched participants from a community-dwelling cohort were randomly
selected. Sera from 284 men were analyzed by enzyme immunoassay for H. pylori
antibodies. Adjusted risk ratio estimation for matched data was conducted to
identify differences. Hispanics had a markedly higher prevalence of infection
(30.3%) than NHWs (9.2%). Matched risk ratio (mRR) analyses revealed a strong
association between H. pylori seropositivity and Hispanic ethnicity (mRR = 3.31;
95% CI [1.91, 5.73], adjusted by BMI, smoking status, and family history of
cancer (mRR range = 3.28-3.89). BMI mRRs (range = 1.19-1.22) were significant in
all models. In this cohort, Hispanic men had higher H. pylori infection rates
than NHWs, and parallel the disproportionately higher rates of GA; obesity
contributes to this higher prevalence. Future studies should address country of
origin, acculturation, and other factors influencing obesity to further elucidate
risk of GA in Hispanic populations.
PMID- 28413905
TI - Pre-meal inulin consumption does not affect acute energy intake in overweight and
obese middle-aged and older adults: A randomized controlled crossover pilot
trial.
AB - BACKGROUND: Three-fourths of adults older than 55 years in the United States are
overweight or obese. Prebiotics including inulin-type fructans may benefit with
weight management. AIM: We aimed to investigate the acute effects of pre-meal
inulin consumption on energy intake (EI) and appetite in older adults. METHODS:
Sedentary, overweight or obese middle-aged and older adults ( n = 7, 60.9 +/- 4.4
years, BMI 32.9 +/- 4.3 kg/m2) ingested inulin (10 g) or a water preload before
each test period in a randomly assigned order. EI, appetite and gastrointestinal
symptoms were monitored during the following 24 h. RESULTS: No differences in EI
were noted between conditions (inulin: 14744 +/- 5552 kJ, control: 13924 +/- 4904
kJ, p > 0.05). Rumbling was increased with inulin consumption ( p < 0.05).
CONCLUSION: Pre-meal inulin consumption does not acutely decrease EI or suppress
appetite in older adults. Further research should address individual differences
among diets, eating behaviors, and microbiota profiles.
PMID- 28413906
TI - Development and Validation of the Masculine Attributes Questionnaire.
AB - The present study describes the development and validation of the Masculine
Attributes Questionnaire (MAQ). The purpose of this study was to develop a
theoretically and empirically grounded measure of masculine attributes for sexual
health research with African American young men. Consistent with Whitehead's
theory, the MAQ items were hypothesized to comprise two components representing
reputation-based and respect-based attributes. The sample included 505 African
American men aged 19 to 22 years ( M = 20.29, SD = 1.10) living in resource-poor
communities in the rural South. Convergent and discriminant validity of the MAQ
were assessed by examining the associations of masculinity attributes with
psychosocial factors. Criterion validity was assessed by examining the extent to
which the MAQ subscales predicted sexual risk behavior outcomes. Consistent with
study hypotheses, the MAQ was composed of (a) reputation-based attributes
oriented toward sexual prowess, toughness, and authority-defying behavior and (b)
respect-based attributes oriented toward economic independence, socially approved
levels of hard work and education, and committed romantic relationships.
Reputation-based attributes were associated positively with street code and
negatively related to academic orientation, vocational engagement, and self
regulation, whereas respect-based attributes were associated positively with
academic and vocational orientations and self-regulation. Finally, reputation
based attributes predicted sexual risk behaviors including concurrent sexual
partnerships, multiple sexual partners, marijuana use, and incarceration, net of
the influence of respect-based attributes. The development of the MAQ provides a
new measure that permits systematic quantitative investigation of the
associations between African American men's masculinity ideology and sexual risk
behavior.
PMID- 28413907
TI - Interaction of dextromethorphan hydrobromide with DNA: multispectral,
voltammetric, and molecular docking technology.
PMID- 28413909
TI - Sticking to the (romantic) script: an examination of love life scripts, stories,
and self-reports of normality.
AB - Life scripts represent cultural expectations regarding the events in the
prototypical life whereas life stories represent narrative constructions of the
events occurring in individuals' own lives. In Study 1, we generated an outline
of the love life script and a list of the self-definitional events individuals
tend to associate with their own love lives. Participants were prompted to
produce and rate seven important events in the prototypical love life and several
significant moments from their own love lives. Building upon these descriptive
efforts, in Study 2, we developed self-report measures of perceived and desired
love life normality. These characteristics positively predicted the
conventionality of autobiographical narratives drawn from participants' love life
stories. Furthermore, perceived normality and desired normality were positively
and negatively related to functioning within the romantic domain, respectively.
These results underscore the role love life scripts and love life stories play in
functioning within the romantic domain.
PMID- 28413910
TI - Phenotypic characterization of late onset cardiac amyloidosis caused by the
transthyretin mutation TTRA45S, p.(Ala65Ser).
PMID- 28413908
TI - Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney
diseases: an update.
AB - Epithelial-mesenchymal transition (EMT) is a tightly regulated process by which
epithelial cells lose their hallmark epithelial characteristics and gain the
features of mesenchymal cells. For podocytes, expression of nephrin, podocin, P
cadherin, and ZO-1 is downregulated, the slit diaphragm (SD) will be altered, and
the actin cytoskeleton will be rearranged. Diabetes, especially hyperglycemia,
has been demonstrated to incite podocyte EMT through several molecular mechanisms
such as TGF-beta/Smad classic pathway, Wnt/beta-catenin signaling pathway,
Integrins/integrin-linked kinase (ILK) signaling pathway, MAPKs signaling
pathway, Jagged/Notch signaling pathway, and NF-kappaB signaling pathway. As one
of the most fundamental prerequisites to develop ground-breaking therapeutic
options to prevent the development and progression of diabetic kidney disease
(DKD), a comprehensive understanding of the molecular mechanisms involved in the
pathogenesis of podocyte EMT is compulsory. Therefore, the purpose of this paper
is to update the research progress of these underlying signaling pathways and
expound the podocyte EMT-related DKDs.
PMID- 28413911
TI - Recurrence rate after thoracoscopic surgery for primary spontaneous pneumothorax.
AB - OBJECTIVES: There is an on-going discussion regarding the recurrence rate after
surgery for primary spontaneous pneumothorax by video assisted thoracic surgery
(VATS) or by thoracotomy access. This study aimed to describe the recurrence
rate, and to identify a possible learning curve, following surgery for primary
spontaneous pneumothorax by VATS. DESIGN: All patients who underwent surgery for
primary spontaneous pneumothorax by VATS at Karolinska University Hospital 2004
2013 were reviewed. Preoperative and operative characteristics were obtained from
medical records. Patients were followed-up through telephone interviews or
questionnaires and by review of medical records. The primary outcome of interest
was time to recurrence of pneumothorax requiring intervention. Outcomes were
compared between patients operated during 2004-June 2010 and July 2010-2013.
RESULTS: 219 patients who underwent 234 consecutive procedures were included. The
mean follow-up times were 6.3 and 2.9 years in the early and late period,
respectively. The postoperative recurrence rate in the early period was 16% (11%
25%), 18% (12%-27%), and 18% (12%-27%), at 1, 3 and 5 years, compared to 1.7%
(0.4%-6.8%), 7.6% (3.7%-15%), and 9.8% (4.8%-19%) at 1, 3 and 5 years, in the
late period (p = 0.016). CONCLUSIONS: We found that the recurrence rate after
thoracoscopic surgery for primary spontaneous pneumothorax decreased
significantly during the study period. Our results strongly suggest that
thoracoscopic surgery for pneumothorax involve a substantial learning curve.
PMID- 28413912
TI - The acute effects of baobab fruit ( Adansonia digitata) on satiety in healthy
adults.
AB - BACKGROUND: The baobab fruit is high in both dietary fibre and polyphenols and
therefore may increase satiety. The aim of the study was to measure the effects
of baobab fruit extract on satiety. METHODS: The study was conducted on 20
healthy participants. The study was a one-day single-blind crossover design.
Participants were randomised to either a test smoothie consisting of 15 g of
baobab extract or a control smoothie without the addition of baobab. Subjective
ratings of satiety were taken on visual analogue scales immediately pre
consumption and then post-consumption, and energy intake at a post ad libitum
meal was recorded. RESULTS: Subjective measures of hunger were reduced following
the test smoothie compared with the control ( p < 0.05). There was no significant
difference in calorie intake at an ad libitum meal. CONCLUSIONS: This research
has positive implications for the use of baobab for reducing hunger, possibly
having a positive effect on weight maintenance.
PMID- 28413913
TI - Sertoliform Cystadenoma of the Rete Testis: Report of a Case and Review of the
Literature.
AB - Sertoliform cystadenoma is a rare benign tumor of the rete testis with 8
previously reported cases and an additional 14 cases reported in an abstract
form. It usually presents with a unilateral scrotal mass, clinically and
radiologically indistinguishable from malignant testicular tumors. We report a 39
year-old man who presented with a right testicular mass. The patient underwent
radical inguinal orchiectomy. Grossly, no masses were appreciated. After
histologic examination with subsequent immunohistochemical staining, a
sertoliform cystadenoma of the rete testis was diagnosed.
PMID- 28413914
TI - Prognostic value of the soluble interleukin-2 receptor level after patients with
follicular lymphoma achieve a response to R-CHOP.
AB - OBJECTIVES: Follicular lymphoma (FL) is a clinically and biologically
heterogeneous disease. Therefore, it is important to identify factors that can
predict its clinical outcome. METHODS: We retrospectively evaluated the
usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP
(posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a
complete response (CR) or partial response. With the use of a recursive
partitioning analysis, we determined the cut-off values of post- and pretreatment
sIL-2R levels that were associated with disease progression, which corresponded
to 486.5 and 5405 U/mL, respectively. RESULTS: The high posttreatment sIL-2R
group showed a significantly inferior progression-free survival (PFS) compared to
the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P
= 0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P = 0.034).
Although a multivariate analysis showed that pretreatment sIL-2R, but not
posttreatment sIL-2R, was an independently significant predictive factor for
disease progression, among patients with low pretreatment sIL-2R levels, those
with high posttreatment sIL-2R levels tended to have inferior PFS. There was a
significant trend in PFS among the high pretreatment sIL-2R group, the low pre-
and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL
2R group (P < 0.001). CONCLUSION: Among patients with a low pretreatment sIL-2R
level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level
may help to identify those with a poor prognosis.
PMID- 28413915
TI - Oxidative stress status in congenital hypogonadism: an appraisal.
AB - Patients with hypogonadism are at increased risk of cardiac and metabolic
diseases. However, the pathogenesis of increased cardiometabolic risk in patients
with hypogonadism is not clear. Oxidative stress plays an important role in the
pathogenesis of cardiometabolic diseases. This study aimed to investigate
possible differences in oxidative stress conditions between patients with
hypogonadism and healthy controls. In this study, 38 male patients with
congenital hypogonadotropic hypogonadism (CHH) (mean age: 21.7 +/- 1.6 years) and
44 healthy male controls (mean age: 22.3 +/- 1.4 years) with almost equal body
mass index were enrolled. The demographic parameters, follicle-stimulating
hormone (FSH), luteinizing hormone (LH), total and free testosterone, homeostatic
model assessment of insulin resistance (HOMA-IR) and oxidative stress parameters,
such as superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx) and
malondialdehyde (MDA), were compared between both groups. Compared to the healthy
controls, triglycerides (p = .02), insulin levels, HOMA-IR values, CAT activities
and MDA levels (p < .001 for all) were significantly higher and HDL cholesterol
(p = .04), total and free testosterone, FSH, LH levels and GPx activity were
significantly lower (p < .001 for all) in patients with CHH. There were
significant correlations between total testosterone levels and CAT activity (r =
.33 p = .01), GPx activity (r = .36 p = .007) and MDA (r = -.47 p < .001) levels.
The results of this study showed that young and treatment-naive patients with
congenital hypogonadism had an increased status of oxidative stress.
PMID- 28413916
TI - Extent of allergic inflammation depends on intermittent versus continuous
sensitization to house dust mite.
AB - OBJECTIVE: House dust mite (HDM) exposure is used to model experimental asthma in
mice. However, a direct comparison of inflammatory responses following continuous
versus intermittent HDM exposure has not been reported. Therefore, we
investigated whether the HDM dose at sensitization or challenge affects extent of
inflammation in mice that were either continuously or intermittently sensitized
with HDM. MATERIALS AND METHODS: C57BL/6 mice received either 10 continuous
exposures with 10 MUg HDM per exposure or two intermittent HDM exposures over a
period of two weeks and were subsequently challenged by three instillations with
HDM during the third week. For the intermittent model, mice were sensitized with
1 or 10 MUg HDM and challenged on three consecutive days with 1 or 10 MUg HDM.
Inflammatory cells in the bronchoalveolar lavage fluid and epithelial cell
hyperplasia and mucous cell metaplasia were quantified. RESULTS: Significantly
higher levels of inflammation and mucous cell metaplasia were observed when mice
were sensitized intermittently compared with continuously. Intermittent
sensitization and challenge with 10 MUg HDM caused maximum inflammation, mucous
cell metaplasia, and epithelial cell hyperplasia. However, sensitization with 1
MUg HDM only also showed increased inflammation when challenged with 10 MUg HDM.
DISCUSSION: These findings suggest major differences in adaptive immunity,
depending on the sensitization protocol. CONCLUSIONS: Because of significant
differences, the HDM sensitization protocol should be carefully considered when
designing studies to investigate the underlying mechanisms of immunity in mouse
models of asthma.
PMID- 28413918
TI - Mothers Who Were Neglected in Childhood Show Differences in Neural Response to
Their Infant's Cry.
AB - The present study used functional magnetic resonance imaging to investigate how a
mother's experience of neglect in her own childhood is associated with her neural
response to her infant's distress cues. During scanning, 22 high-risk primiparous
mothers were exposed to both their own 18-month-old infant's cry sound and a
control sound. Mothers' continuous Neglect subscale scores from the Childhood
Trauma Questionnaire were examined as a predictor of their neural response to own
infant cry > control sound. Mothers who reported high levels of neglect from
childhood showed regions of hyperactivation to their infant's cry (relative to
control sound) in the anterior and posterior cingulate cortices and insula as
well as specific prefrontal (precentral gyrus) and parietal (posterior
supramarginal gyrus) areas. These results may suggest how important early life
experiences are for future parenting responses and behaviors.
PMID- 28413919
TI - Examining Child Welfare Decisions and Services for Asian-Canadian Versus White
Canadian Children and Families in the Child Welfare System.
AB - Using administrative child welfare data from the Ontario Child Abuse and Neglect
Data System (OCANDS), this study compared the profiles of Asian-Canadian and
White-Canadian children and families that experienced a case closure after an
investigation instead of being transferred to ongoing child protection services
(CPS). Child protection investigations involving Asian-Canadian and White
Canadian children and families that were transferred to ongoing CPS presented a
different profile of case characteristics and caregiver and child clinical needs.
Asian-Canadian children and families received ongoing CPS for over a month longer
than White-Canadian children and families and were less likely (odds ratio [ OR]
= 0.39) to be reinvestigated for any form of maltreatment-related concerns within
1 year after case closure. It appears that child protection investigations
involving Asian-Canadian children and families are less likely to be closed
prematurely than White-Canadian children and families, and the child protection
system may be meeting the needs of Asian-Canadian communities. Alternatively, it
is possible there is unaccounted biases that may be reflective of systemic
problem of discriminative practices in the child protection system. Further
research is needed to explore this phenomenon.
PMID- 28413917
TI - Is the Families First Home Visiting Program Effective in Reducing Child
Maltreatment and Improving Child Development?
AB - While home visiting programs are among the most widespread interventions to
support at-risk families, there is a paucity of research investigating these
programs under real-world conditions. The effectiveness of Families First home
visiting (FFHV) was examined for decreasing rates of being in care of child
welfare, decreasing hospitalizations for maltreatment-related injuries, and
improving child development at school entry. Data for 4,562 children from home
visiting and 5,184 comparison children were linked to deidentified administrative
health, social services, and education data. FFHV was associated with lower rates
of being in care by child's first, second, and third birthday (adjusted risk
ratio [aRR] = 0.75, 0.79, and 0.81, respectively) and lower rates of
hospitalization for maltreatment-related injuries by third birthday (aRR = 0.59).
No differences were found in child development at kindergarten. FFHV should be
offered to at-risk families to decrease child maltreatment. Program enhancements
are required to improve child development at school entry.
PMID- 28413920
TI - First Births to Maltreated Adolescent Girls: Differences Associated With Spending
Time in Foster Care.
AB - Few studies have examined early parenting among girls receiving child welfare
services (CWS) or disentangled the relationship between maltreatment, spending
time in foster care, and adolescent childbirth. Using population-based, linked
administrative data, this study calculated birth rates among maltreated
adolescent girls and assessed differences in birth rates associated with spending
time in foster care. Of the 85,766 girls with substantiated allegations of
maltreatment during adolescence, nearly 18% subsequently gave birth. Among girls
who spent time in foster care, the proportion was higher (19.5%). Significant
variations ( p < .001) were observed in the rate of childbirth across demographic
characteristics and maltreatment experiences. When accounting for all of the
covariates, spending time in foster care was associated with a modestly higher
rate of a first birth (Hazard Ratio [HR] = 1.10; 95% confidence interval = [1.06,
1.14]). While age at first substantiated allegation of maltreatment and
race/ethnicity were significant predictors of adolescent childbirth, specific
maltreatment experiences were associated with minimal or no differences in birth
rates. The findings of this study suggest that the experience of spending time in
care may not be a meaningful predictor of giving birth as a teen among CWS
involved adolescent girls and highlight subgroups of this population who may be
more vulnerable to early childbirth.
PMID- 28413922
TI - Child Maltreatment Welcomes New Board Members.
PMID- 28413921
TI - Preventing the Onset of Child Sexual Abuse by Targeting Young Adolescents With
Universal Prevention Programming.
AB - Child sexual abuse (CSA) is a serious public health problem that increases risk
for physical and mental health problems across the life course. Young adolescents
are responsible for a substantial portion of CSA offending, yet to our knowledge,
no validated prevention programs that target CSA perpetration by youth exist.
Most existing efforts to address CSA rely on reactive criminal justice policies
or programs that teach children to protect themselves; neither approach is well
validated. Given the high rates of desistance from sexual offending following a
youth's first CSA-related adjudication, it seems plausible that many youth could
be prevented from engaging in their first offense. The goal of this article is to
examine how school-based universal prevention programs might be used to prevent
CSA perpetrated by adolescents. We review the literature on risk and protective
factors for CSA perpetration and identify several promising factors to target in
an intervention. We also summarize the literature on programs that have been
effective at preventing adolescent dating violence and other serious problem
behaviors. Finally, we describe a new CSA prevention program under development
and early evaluation and make recommendations for program design characteristics,
including unambiguous messaging, parental involvement, multisession dosage,
skills practice, and bystander considerations.
PMID- 28413923
TI - Knowledge of healthy foods does not translate to healthy snack consumption among
exercise science undergraduates.
AB - This cross-sectional survey study compared the on- and off-campus snack choices
and related correlates of convenience samples of exercise science (ES) ( n = 165,
M = 45%, F = 55%) and non-exercise science (NES) ( n =160, M = 43%, F = 57%)
undergraduates. The hypothesis posed was that knowledge of healthy foods will not
translate to healthier snack consumption by the ES students, and that the snack
choices and related correlates of ES and NES students will be similar. Data were
collected using self-administered questionnaires completed in classrooms (ES
sample) and at high-traffic locations on-campus (NES sample). Chi-square and t
test analyses compared ES and NES students on snack correlates. Snacks consumed
most often by the ES and NES students on-campus were health bars/squares ( n = 56
vs. n = 48) and savory snacks ( n = 55 vs. n = 71), and off-campus were savory
snacks ( n = 60 vs. n = 71) and fruits ( n = 41 vs. n = 34). Over half of both
samples believed their snack choices were a mix of unhealthy and healthy. Fruits
were considered healthier snacks and chips less healthy by both samples, and
fruits were the most often recommended snack. About 20% believed these choices
would impact their health unfavorably, and about two thirds self-classified in
the action stages for healthy snacking. Since knowledge about healthy food
choices did not translate to healthy snack selection, these students would
benefit from interventions that teach selection and preparation of healthy snacks
on a restricted budget.
PMID- 28413924
TI - Erythropoietin attenuates axonal injury after middle cerebral artery occlusion in
mice.
AB - OBJECTIVE: Erythropoietin (EPO) confers potent neuroprotection against ischemic
injury through a variety of mechanisms. However, the protective effect of EPO on
axons after cerebral ischemia in adult mice is rarely covered. The purpose of
this study was to investigate the potential neuroprotective effects of EPO on
axons in mice after cerebral ischemia. METHODS: A total of 30 adult male C57 BL/6
mice were treated with EPO (5000 IU/kg) or vehicle after transient middle
cerebral artery occlusion (MCAO). The mortality rate of each experimental group
was calculated. Neurological function was assessed by Rota-rod test. Frozen
sections from each mouse brain at 14 days after reperfusion were used to evaluate
the fluorescent intensity of myelin basic protein (MBP) and neurofilament 200 (NF
200). Immunofluorescence staining and Western blotting were used to assess the
protein level of beta-amyloid precursor protein (beta-APP) and glial fibrillary
acidic protein (GFAP), a marker of mature astrocytes. The protein levels of the
myelin-derived growth inhibitory proteins, neurite growth inhibitor-A (Nogo-A),
myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein
(OMG) were also examined by Western blot after MCAO. RESULTS: The survival rate
of the vehicle group 14 days after cerebral ischemia-reperfusion was 50%, which
increased to 80% after EPO treatment at the start of reperfusion. EPO improved
neurobehavioral outcomes at days 3 and 7 after MCAO was compared with the vehicle
group (P < 0.05). Furthermore, EPO ameliorated demyelination, demonstrated by
upregulation of the MBP/NF-200 ratio. Meanwhile, increased levels of beta-APP,
GFAP, Nogo-A, and MAG after MCAO were reduced by EPO treatment (P < 0.05).
CONCLUSION: EPO treatment attenuates axonal injury and improves neurological
function after cerebral ischemia in adult mice.
PMID- 28413925
TI - Triple-Bead Mixed Amphetamine Salts (SHP465) in Adults With ADHD: Results of a
Phase 3, Double-Blind, Randomized, Forced-Dose Trial.
AB - OBJECTIVE: Evaluate the efficacy and tolerability of triple-bead mixed
amphetamine salts (MAS) in ADHD. METHOD: Adults with ADHD Rating Scale IV (ADHD
RS-IV) total scores >=32 were randomized to 6 weeks of triple-bead MAS (25, 50,
or 75 mg) or placebo. The primary endpoint was ADHD-RS-IV total score change from
baseline at end of study (EOS). RESULTS: Least squares mean (95% confidence
interval [CI]) treatment differences for ADHD-RS-IV total score changes from
baseline to EOS significantly favored triple-bead MAS (all doses combined: -10.6
[-13.2, -8.0]; p < .0001); there were no significant differences between triple
bead MAS dosages. The most frequently reported TEAEs with triple-bead MAS (all
doses combined) included insomnia, decreased appetite, and dry mouth. Mean +/- SD
pulse and systolic blood pressure increases at EOS were 3.5 +/- 10.33 bpm and 0.3
+/- 10.48 mmHg with triple-bead MAS (all doses combined). CONCLUSION: Triple-bead
MAS significantly reduced adult ADHD symptoms; the safety profile was consistent
with previous triple-bead MAS studies.
PMID- 28413926
TI - DUSP-1 gene expression is not regulated by promoter methylation in diabetes
associated cardiac hypertrophy.
AB - BACKGROUND: The exact mechanism causing decreased expression of the dual specific
phosphatase-1 ( DUSP-1) gene in diabetes-associated cardiac hypertrophy is not
known. DNA promoter methylation is often associated with decreased gene
expression in many diseases including cardiovascular diseases. So, we
investigated whether epigenetic silencing via promoter methylation is involved in
the decreased expression of DUSP-1 in diabetes-associated cardiac hypertrophy.
METHODS: Real-time polymerase chain reaction (PCR) and Western blotting confirmed
the down regulation of the DUSP-1 gene at transcriptional and translational
levels. Bisulfite-converted DNA samples from myocardium of rat model of diabetic
cardiomyopathy (DCM), high glucose (HG)-treated neonatal rat cardiomyocytes
(NRCMs) and cardiac tissues from archived human myocardial DCM autopsies along
with their respective controls were analyzed for methylation in the promoter
region of the DUSP-1 gene. RESULTS: We observed no methylation in the promoter
regions of the DUSP-1 gene in DCM rat hearts, in HG-treated NRCMs (between -355
bp and -174 bp) and in cardiac tissues from archived human myocardial DCM
autopsies (between -274 bp and -73 bp). CONCLUSION: Methylation-mediated
silencing of the DUSP-1 promoter does not appear to be associated with reduced
expression, indicating the involvement of other factors in specific suppression
of DUSP-1 in diabetes-associated cardiac hypertrophy.
PMID- 28413927
TI - "It Has Changed My Life": An Exploration of Caregiver Experiences in Serious
Illness.
AB - BACKGROUND: Informal, unpaid caregivers shoulder much of the care burden for
individuals with serious illness. As part of a project to create an innovative
model of supportive care for serious illness, a series of user interviews were
conducted, forming the basis for this article. OBJECTIVE: To understand both
individual and interpersonal aspects of caregiving for serious illness. METHODS:
Twelve semistructured group interviews were conducted with patients, families,
and professionals as part of a larger study of late-life serious illness.
Transcript data were analyzed with descriptive coding, and then coded material
was analyzed to elicit major themes and subthemes. RESULTS: A total of 73
individuals participated in group interview sessions. Using descriptive coding,
quotes were assigned to first-order codes of rewards, challenges, and a category
of learnings and adaptations. Subthemes of reward included gratitude, a sense of
accomplishment or mastery, and closeness in personal relationships. The most oft
cited challenges included emotional and physical stresses of caregiving and
feeling unprepared or unsupported in caregiving. Reflecting on their experiences,
caregivers cited new ways in which they had learned to be creative, to show
assertiveness and advocacy, and to create personal balance in a demanding
situation. CONCLUSIONS: The experience of caregiving is a life-altering journey
as individuals rise to challenges and reflect on the rewards. Caregivers
described intensive caregiving, often without acknowledgment or understanding of
their role from the health-care system. This invisibility created its own
iatrogenic caregiving challenge. The identified themes suggest avenues of
meaningful caregiver support that bear further exploration.
PMID- 28413928
TI - The Oncology Specialist's Role in POLST Form Completion.
AB - INTRODUCTION: Patients with cancer and oncology professional societies believe
that advance care planning is important, but we know little of who actually has
this conversation. Physician Orders for Life-Sustaining Treatment (POLST) forms
can help to document these important conversations to ensure patients receive the
level of treatment they want. We therefore sought to determine the specialty of
those signing POLST forms for patients who died of cancer to better understand
who is having this discussion with patients. METHODS: Retrospective cohort study
including all deaths due to cancer in Oregon between January 1, 2010, and
December 31, 2011. Death certificates were matched to POLST forms in the Oregon
POLST Registry, and the signing physician's specialty was determined using the
Oregon Medical Board's database. RESULTS: A total of 14 979 people died of cancer
in Oregon in 2010 to 2011. Of which, 6145 (41.0%) had at least 1 POLST form in
the Registry. Oncology specialists signed 14.9% of POLST forms, compared to 53.7%
by primary care, 15.3% by hospice/palliative care, 12.8% by advanced practice
providers, and 2.7% by other specialists; 51.8% of oncology specialists did not
sign a POLST form, whereas 12.5% completed 10 or more. CONCLUSION: Oncology
specialists play a central role in caring for patients with cancer through the
end of their lives, but not in POLST completion. Whether or not they actually
sign their patients' POLST forms, oncology specialists in the growing number of
POLST states should integrate POLST into their goals of care conversations with
patients nearing the end of life.
PMID- 28413929
TI - Nurses' Interest in Independently Initiating End-of-Life Conversations and
Palliative Care Consultations in a Suburban, Community Hospital.
AB - BACKGROUND: Patients who receive early palliative care consults have clinical
courses and outcomes more consistent with their goals. Nurses have been shown to
be advocates for early palliative care involvement and are able to lead advanced
care planning discussions. OBJECTIVE: The purpose of this study was to assess
whether after a brief educational session, nurses at a suburban, community
hospital could demonstrate knowledge of palliative care principles, would want to
independently initiate end-of-life conversations with patients and families, and
would want to place specialty palliative care consults. DESIGN: Four 1 hour
presentations were made at 4 nursing leadership council meetings from November
through December 2015. Anonymous pre- and post-presentation surveys were
distributed and collected in person. Setting/Participant: Nonprofit, suburban,
community hospital in Maryland. Participants were full-time or part-time hospital
employees participating in a nursing leadership council who attended the
presentation. MEASUREMENTS: We compared responses from pre- and post-presentation
surveys. RESULTS: Fifty nurses (19 departments) completed pre-presentation
surveys (100% response rate) and 49 nurses completed post-presentation surveys
(98% response rate). The average score on 7 index questions increased from 71% to
90%. After the presentations, 86% strongly agreed or agreed that nurses should be
able to independently order a palliative care consult and 88% strongly agreed or
agreed with feeling comfortable initiating an end-of-life conversation.
CONCLUSION: Brief educational sessions can teach palliative care principles to
nurses. Most participants of the study would want to be able to directly consult
palliative care and would feel comfortable initiating end-of-life conversations
after this educational session.
PMID- 28413930
TI - Relationship of Genetic Variants With Procedural Pain, Anxiety, and Distress in
Children.
AB - OBJECTIVE: This study used a candidate gene approach to examine genomic variation
associated with pain, anxiety, and distress in children undergoing a medical
procedure. STUDY DESIGN: Children aged 4-10 years having an IV catheter insertion
were recruited from three Midwestern children's hospitals. Self-report measures
of pain, anxiety, and distress were obtained as well as an observed measure of
distress. Samples were collected from children and biological parents for
analysis of genomic variation. Genotyped variants had known or suspected
association with phenotypes of interest. Analyses included child-only association
and family-based transmission disequilibrium tests. RESULTS: Genotype and
phenotype data were available from 828 children and 376 family trios. Children
were 50% male, had a mean age of 7.2 years, and were 84% White/non-Hispanic. In
family-based analysis, one single-nucleotide polymorphism (SNP; rs1143629,
interleukin ( IL1B) 1beta) was associated with observed child distress at
Bonferroni-corrected levels of significance ( p = .00013), while two approached
significance for association with high state anxiety (rs6330 Nerve Growth Factor,
Beta Subunit, [ NGFB]) and high trait anxiety (rs6265 brain-derived neurotrophic
factor [ BDNF]). In the child-only analysis, multiple SNPs showed nominal
evidence of relationships with phenotypes of interest. rs6265 BDNF and rs2941026
cholecystokinin B receptor had possible relationships with trait anxiety in child
only and family-based analyses. CONCLUSIONS: Exploring genomic variation furthers
our understanding of pain, anxiety, and distress and facilitates genomic
screening to identify children at high risk of procedural pain, anxiety, and
distress. Combined with clinical observations and knowledge, such explorations
could help guide tailoring of interventions to limit procedure-related distress
and identify genes and pathways of interest for future genotype-phenotype
studies.
PMID- 28413931
TI - Glucose Variations and Activity Are Strongly Coupled in Sleep and Wake in Young
Adults With Type 1 Diabetes.
AB - BACKGROUND: Glucose variations are common throughout sleep and wakefulness in
people with type 1 diabetes mellitus (T1DM). The objective of this investigation
was to characterize the time-varying coupling between glucose and unstructured
physical activity over a 60-hr period in young adults with T1DM. The hypothesis
was that coupling would differ during sleep versus wakefulness and would exhibit
circadian variations. METHOD: Young adults with T1DM treated with an insulin pump
participated in the study. Glucose variations were monitored with a continuous
glucose monitoring system, and activity was assessed using an activity-monitoring
band worn on the nondominant wrist. Simultaneous glucose and physical activity
data across a continuous 60-hr period were used for analysis. Wavelet coherence
analysis was employed to quantify the coupling between physical activity and
glucose. Cosinor analysis was used to assess whether glucose/activity coherence
exhibited significant circadian variations. RESULTS: Participants comprised 23
adults, aged 18-30 years, with T1DM. Coherence analysis demonstrated substantial
coupling between physical activity and glucose variations during both wakefulness
and sleep. For rapid (10-30 min) fluctuations, mean coherence was higher during
sleep than wakefulness ( F = 10.86, p = .003). Rapid glucose variations
consistently led to changes in activity ( p = .001) during sleep but not during
wake. Cosinor analysis revealed significant circadian modulation of
glucose/activity coupling, especially for fluctuation periods 2-4 hr.
CONCLUSIONS: Unstructured physical activity and glucose variations demonstrated
strong time- and frequency-dependent coupling over a 60-hr period in young adults
with T1DM, with sleep/wake differences and circadian modulation evident in this
relationship.
PMID- 28413933
TI - Primer in Genetics and Genomics, Article 3-Explaining Human Diversity: The Role
of DNA.
AB - Genetic variation lays the foundation for diversity and enables humans to adapt
to changing environments. The order of the nucleotides adenine, guanine,
cytosine, and thymine on the deoxyribonucleic acid (DNA) molecules of the nuclear
chromosomes and mitochondrial DNA (mtDNA) plays an important role in normal cell
division, tissue development, and reproduction but is susceptible to alteration
from a large number of random, inherited, or environmental events. Variations can
range from a change in a single nucleotide to duplication of entire chromosomes.
Single nucleotide polymorphisms are the major source of human heterogeneity.
Other variations that can alter phenotypes and adversely impact growth,
development, and health include copy number variations, aneuploidies, and
structural alterations such as deletions, translocations, inversions,
duplications, insertions, or mutations in mtDNA. In addition, DNA rearrangements
in somatic cells underlie the uncontrolled cell growth found in cancer. This
article explores the mechanisms by which variations in DNA arise and the impact
those changes can have on human health.
PMID- 28413934
TI - Commonly used air filters fail to eliminate secondhand smoke induced oxidative
stress and inflammatory responses.
AB - Secondhand smoke (SHS) causes approximately 50,000 deaths per year. Despite all
the health warnings, smoking is still allowed indoors in many states exposing
both workers and patrons to SHS on a daily basis. The opponents of smoking bans
suggest that present day air filtration systems remove the health hazards of
exposure to SHS. In this study, using an acute SHS exposure model, we looked at
the impact of commonly used air filters (MERV-8 pleated and MERV-8 pleated
activated charcoal) on SHS by assessing the inflammatory response and the
oxidative stress response in C57BL/6 mice. In order to assess the inflammatory
response, we looked at the tumor necrosis factor alpha (TNF-alpha) cytokine
production by alveolar macrophages (AMs), and for the oxidative response, we
quantified the products of lipid peroxidation and the total glutathione (tGSH)
production in lung homogenates. Our results showed that SHS caused significant
immune and oxidative stress responses. The tested filters resulted in only a
modest alleviation of inflammatory and oxidative responses due to SHS exposure.
Our data show that these air filters cannot eliminate the risk of SHS exposure
and that a short-term exposure to SHS is sufficient to alter the inflammatory
cytokine response and to initiate a complex oxidative stress response. Our
results are consistent with the statement made by the Surgeon General's reports
that there is no risk free level of exposure to SHS.
PMID- 28413935
TI - Predictive validity of the K-SADS-PL 2009 version in school-aged and adolescent
outpatients.
AB - BACKGROUND: The schedule for affective disorders and schizophrenia for school-age
children (K-SADS) is one of the most commonly used standardized diagnostic
interviews in child and adolescent psychiatry. Validity studies are scarce, and
limited to concurrent validity with other measures and clinical diagnoses. AIMS:
To evaluate the K-SADS interview in an outpatient child and adolescent psychiatry
(CAP) setting with a Longitudinal Expert All Data (LEAD) procedure. METHODS: CAP
residents performed a K-SADS-PL interview with the revised 2009 version
containing the new PDD section on 239 clinically referred outpatients of 6-17
years old and their parent(s). A consensus LEAD diagnosis by two senior
clinicians 1.2 (SD = 0.6) years later was based on clinical records including the
K-SADS and subsequent information from further assessments, information from
teachers and other informants, outcome of treatment, and at least three visits
after the K-SADS. RESULTS: Predictive validity for K-SADS vs LEAD diagnoses were
good-to-excellent for broader categories of anxiety disorders (kappa = 0.94),
depressive (kappa = 0.91), behavioural (kappa = 0.91) and tic (kappa = 0.81)
disorders, good for ADHD (kappa = 0.80), and good-to-moderate for autism spectrum
disorders (kappa = 0.62). Bipolar, psychotic, and eating disorders were too few
to be analysed. CONCLUSION: The K-SADS diagnoses elicited from an interview with
the child and one from parents on one occasion have an excellent validity for
most major child psychiatric disorders. ADHD can be reliably diagnosed at one
visit, but clinicians need to stay alert for possible undiagnosed ADHD.
Diagnosing autism with K-SADS-PL 2009 version at one visit is not advisable.
PMID- 28413936
TI - Processing speed can monitor stimulant-medication effects in adults with
attention deficit disorder with hyperactivity.
AB - BACKGROUND: Treatment responses to methylphenidate by adults with ADHD are
generally monitored against DSM-IV/DSM-V symptomatology, rating scales or
interviews during reviews. AIMS: To evaluate the use of single- and dual
dimension processing-speed and efficiency measures to monitor the effects of
pharmacological treatment with methylphenidate after a short period off
medication. METHODS: A Quick Test of Cognitive Speed (AQT) monitored the effects
of immediate-release methylphenidate in 40 previously diagnosed and medicated
adults with ADHD. Processing speed was evaluated with prior prescription
medication, without medication after a 2-day period off ADHD medication, and with
low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride
(Medikinet IR). RESULTS: Thirty-three participants responded to the experimental
treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant
main effects for single dimension colour and form and dual-dimension colour-form
naming. Post-hoc analysis indicated statistical differences between the no- and
high-dose medication conditions for colour and form, measures of perceptual
speed. For colour-form naming, a measure of cognitive speed, there was a
significant difference between no- and low-dose medication and between no- and
high-dose medications, but not between low- and high-dose medications.
CONCLUSIONS: Results indicated that the AQT tests effectively monitored
incremental effects of the methylphenidate dose on processing speed after a 2-day
period off medication. Thus, perceptual (colour and form) and cognitive speed
(two-dimensional colour-form naming) and processing efficiency (lowered shift
costs) increased measurably with high-dose medication. These preliminary findings
warrant validation with added measures of associated behavioural and cognitive
changes.
PMID- 28413937
TI - Alexithymia and depression in the recovery of chronic pain patients: a follow-up
study.
AB - BACKGROUND: Childhood adversities and emotional dysregulation are connected with
chronic pain, alexithymia, and depression. Longitudinal studies exploring the
impact of their co-occurrence on the pain situation are rare. AIMS: The influence
of alexithymia, depression, baseline pain situation, and treatment options on the
course of chronic pain in a clinical sample was studied. METHODS: The baseline
data was collected from chronic pain patients (n = 154) before their first pain
clinic visit, and the follow-up data after 1 year by self-report questionnaires.
Study variables consisted of pain intensity, pain disability, alexithymia (TAS
20), depression (BDI-II), and treatment interventions. Statistical analyses were
performed to find out differences between baseline and follow-up, as well as
between alexithymic and non-alexithymic patients, and to estimate the effect of
the treatment provided. RESULTS: At follow-up, the majority of the patients had
pain intensity and disability severe enough to disrupt with their daily living.
None of treatment interventions was related to better outcome. Alexithymic
patients reported more pain disability and depression at both baseline and at
follow-up. The effect of alexithymia on pain disability was mediated by
depression. The use of opioids was connected to alexithymia and depressiveness.
Alexithymia and depression made a substantial contribution to poorer outcome.
CONCLUSIONS: Severe pain intensity and disability with depression and alexithymia
predicted difficulties in achieving improvement. Depression and alexithymia
probably impair compliance with treatment and adherence to interventions. Their
co-occurrence with a more severe pain situation and with the use of opioids
indicates psychological problems underlying the pain experience.
PMID- 28413938
TI - Psychiatric service users' experiences of emergency departments: a CERQual review
of qualitative studies.
AB - BACKGROUND: There is increased clinical and political attention towards
integrating general and psychiatric emergency departments (ED). However, research
into psychiatric service users' experiences regarding general EDs is limited.
AIM: To identify and summarize current, qualitative evidence regarding service
users' experiences attending EDs. A secondary aim is to apply and test the newly
developed CERQual approach to summarizing qualitative review findings. METHODS: A
systematic literature review of five databases based on PRISMA guidelines yielded
3334 unique entries. Screening by title/abstract identified 57 studies and, after
full text assessment, nine studies were included. The included studies were
critically appraised using CASP. Thematic synthesis was applied for data
extraction and identification of findings. The CERQual approach was utilized to
assess the confidence of the findings. RESULTS: The results of the review showed
moderate confidence in the findings that service users experience meeting caring
and judgmental ED staff, and that waiting times and a stressful environment are
integral to their ED experiences. In contrast, low-to-very low confidence was
seen in the findings that service users experience having their symptoms ignored
and that EDs are used due to a lack of alternatives. A companion may improve
service users experience and outcome of ED visits. CONCLUSION: Service users
experience stress and discomfort in the ED. Service users highly appreciate
knowing staff who can ease the discomfort. Overall, the results of this review
speak in favour of integrated EDs where service users' needs are more likely to
be recognized and accommodated.
PMID- 28413940
TI - Elevated mRNA expression of CASPR3 in patients with schizophrenia.
AB - BACKGROUND: Recently, it was reported that antipsychotic treatment reverted
Contactin Associated Protein-Like 3 (CASPR3, same as CNTNAP3) mRNA expressions in
leukocytes of schizophrenia (SCZ) subjects to the same levels as healthy
controls. CASPR3 was expressed in various regions of the mice brain (cortex,
frontal lobes, corpus callosum, hippocampus, etc.). Thus, this study evaluated
CASPR3 mRNA expression in SCZ subjects to find a new clue of schizophrenia
pathogenesis. METHODS: One hundred SCZ subjects and 100 age-matched controls were
compared. Levels of CASPR3 mRNA in leukocytes were analysed with a quantitative
real-time PCR method using TaqMan probes. RESULTS: CASPR3 mRNA expression was
significantly higher in leukocytes of SCZ subjects than controls. However, there
were no significant correlations between expression level and any clinical
parameters in 50 SCZ subjects. CONCLUSION: Considering that CASPR3 is involved in
building the brain neural network and autophagy in circulating leukocytes,
abnormal CASPR3 expression in SCZ subjects may be associated with the
pathogenesis of SCZ.
PMID- 28413941
TI - Psychobiological Protective Factors Modifying the Association Between Age and
Sexual Health in Men: Findings From the Men's Health 40+ Study.
AB - Sexual health severely decreases with age. For males older than 40 years,
erectile dysfunction (ED) is the most common sexual disorder. Although physical
and psychological risk factors for ED have been identified, protective factors
are yet to be determined. To date, no study has examined endocrine and
psychosocial factors in parallel with regard to their modifying effect on the age
related increase in ED. Two hundred and seventy-one self-reporting healthy men
aged between 40 and 75 years provided both psychometric data on sexual function
and a set of potential psychosocial protective factors, and saliva samples for
the analysis of steroid hormones and proinflammatory cytokines. Around 35% of the
participants reported at least a mild form of ED. Direct associations with ED
were identified for perceived general health, emotional support, relationship
quality, intimacy motivation but not for steroid hormones or proinflammatory
markers. Moderation analyses for the association between age and ED revealed
positive effects for testosterone (T), dehydroepiandrosterone (DHEA), perceived
general health, emotional support, intimacy motivation, and a negative effect for
interleukin-6 (all p < .05; f2 > .17). Group differences between older men with
and without ED emerged for T, DHEA, and psychometric measures such as perceived
general health, emotional support, satisfaction with life, and intimacy
motivation (all p < .05; d > .3). Both psychosocial and endocrine parameters
moderated the association between age and sexual health. Perceived general
health, emotional support, intimacy motivation, and relationship quality emerged
as psychosocial protective factors against ED. Higher T and DHEA and lower
interleukin-6 levels also buffered against an age-related increase in ED.
PMID- 28413942
TI - Barriers to Offering Vasectomy at Publicly Funded Family Planning Organizations
in Texas.
AB - Few publicly funded family planning clinics in the United States offer vasectomy,
but little is known about the reasons this method is not more widely available at
these sources of care. Between February 2012 and February 2015, three waves of in
depth interviews were conducted with program administrators at 54 family planning
organizations in Texas. Participants described their organization's vasectomy
service model and factors that influenced how frequently vasectomy was provided.
Interview transcripts were coded and analyzed using a theme-based approach.
Service models and barriers to providing vasectomy were compared by organization
type (e.g., women's health center, public health clinic) and receipt of Title X
funding. Two thirds of organizations did not offer vasectomy on-site or pay for
referrals with family planning funding; nine organizations frequently provided
vasectomy. Organizations did not widely offer vasectomy because they could not
find providers that would accept the low reimbursement for the procedure or
because they lacked funding for men's reproductive health care. Respondents often
did not perceive men's reproductive health care as a service priority and
commented that men, especially Latinos, had limited interest in vasectomy.
Although organizations of all types reported barriers, women's health centers and
Title X-funded organizations more frequently offered vasectomy by conducting
tailored outreach to men and vasectomy providers. A combination of factors
operating at the health systems and provider level influence the availability of
vasectomy at publicly funded family planning organizations in Texas. Multilevel
approaches that address key barriers to vasectomy provision would help
organizations offer comprehensive contraceptive services.
PMID- 28413943
TI - Assessment on Occurrences of Depression and Anxiety and Associated Risk Factors
in the Infertile Chinese Men.
AB - The prevalence of depression and anxiety in the Chinese male population with
infertility is still uncertain. The prevalence of depression, anxiety, and a
combination of both psychological symptoms was 20.8%, 7.8%, and 15.4%,
respectively in 771 infertile Chinese men in the current study by the Mental
Health Inventory-5 and the State-Trait Anxiety Inventory-Short Form
questionnaires. Differences in demographics (age, education, and income) had no
noticeable impact on the development of psychological symptoms. Clinical factors
such as concomitant disorders (varicocele, epididymal cyst, and erectile
dysfunction) were identified as risk factors associated with depressive symptoms
( OR = 1.47; 95% CI [1.14, 1.90]; p < .001) and both depressive and anxiety
symptoms ( OR = 1.56; 95% CI [1.17, 2.08]; p < .001). An infertility duration
over 2 years was associated with a high risk of anxiety symptoms ( OR = 3.94; 95%
CI [1.20, 12.93], p < .02). Other clinical conditions such as type of treatment
and quality of sperm were not significant risk factors for psychological
symptoms. This study provides evidence that Chinese men of reproductive age who
suffer from infertility are vulnerable to psychological distress.
PMID- 28413944
TI - The Assessment of Motor Fatigability in Persons With Multiple Sclerosis: A
Systematic Review.
AB - BACKGROUND: Persons with multiple sclerosis (PwMS) are often characterized by
increased motor fatigability, which is a performance change on an objectively
measured criterion after any type of voluntary muscle contractions. This review
summarizes the existing literature to determine which protocols and outcome
measures are best to detect or study motor fatigability and the underlying
mechanisms in MS. METHODS: Two electronic databases, PubMed and Web of Science,
were searched for relevant articles published until August 2016 with a
combination of multiple sclerosis, fatigability, muscle fatigue, and motor
fatigue. RESULTS: A total of 48 articles were retained for data extraction. A
variety of fatigability protocols were reported; protocols showed differences in
type (isometric vs concentric), duration (15 to 180 s), and number of
contractions (fixed or until exhaustion). Also, 12 articles reported motor
fatigability during functional movements, predominantly assessed by changes in
walking speed; 11 studies evaluated the mechanisms underlying motor fatigability,
using additional electrical nerve or transcranial magnetic stimulation. Three
articles reported psychometrics of the outcomes. CONCLUSIONS: The disparity of
protocols and outcome measures to study different aspects of motor fatigability
in PwMS impedes direct comparison between data. Most protocols use maximal single
joint isometric contractions, with the advantage of high standardization. Because
there is no head-to-head comparison of the different protocols and only limited
information on psychometric properties of outcomes, there is currently no gold
standard to assess motor fatigability. The disability level, disease phenotype,
and studied limb may influence the assessment of motor fatigability in PwMS.
PMID- 28413946
TI - Kinetics of Ligand Binding Through Advanced Computational Approaches: A Review.
AB - Ligand residence times and binding rates have been found to be useful quantities
to consider during drug design. The underlying structural and dynamic
determinants of these kinetic quantities are difficult to discern. Driven by
developments in computational hardware and simulation methodologies, molecular
dynamics (MD) studies on full binding and unbinding pathways have emerged
recently, showing these structural and dynamic determinants in atomic detail.
However, the long timescales related to drug binding and release are still
prohibitive to conventional MD simulation. Here we discuss a suite of enhanced
sampling methods that have been applied to the study of full ligand binding or
unbinding pathways, and reveal the kinetics of drug binding and/or release. We
divide these sampling methods into three families (trajectory parallelization,
metadynamics, and temperature- based methods), and discuss recent applications of
each, as well as their basic theoretical underpinnings including how kinetic
information is extracted. We then present an outlook for how the field could
evolve, and how the rich variety of sampling methods discussed here can be
leveraged in the future for computationally driven drug design.
PMID- 28413945
TI - Body-Machine Interface Enables People With Cervical Spinal Cord Injury to Control
Devices With Available Body Movements: Proof of Concept.
AB - This study tested the use of a customized body-machine interface (BoMI) for
enhancing functional capabilities in persons with cervical spinal cord injury
(cSCI). The interface allows people with cSCI to operate external devices by
reorganizing their residual movements. This was a proof-of-concept phase 0
interventional nonrandomized clinical trial. Eight cSCI participants wore a
custom-made garment with motion sensors placed on the shoulders. Signals derived
from the sensors controlled a computer cursor. A standard algorithm extracted the
combinations of sensor signals that best captured each participant's capacity for
controlling a computer cursor. Participants practiced with the BoMI for 24
sessions over 12 weeks performing 3 tasks: reaching, typing, and game playing.
Learning and performance were evaluated by the evolution of movement time,
errors, smoothness, and performance metrics specific to each task. Through
practice, participants were able to reduce the movement time and the distance
from the target at the 1-second mark in the reaching task. They also made
straighter and smoother movements while reaching to different targets. All
participants became faster in the typing task and more skilled in game playing,
as the pong hit rate increased significantly with practice. The results provide
proof-of-concept for the customized BoMI as a means for people with absent or
severely impaired hand movements to control assistive devices that otherwise
would be manually operated.
PMID- 28413947
TI - Novel Signaling Interface Constituted with Membrane Receptor-Like Kinases Emerged
from the Study of Interaction and Transphosphorylation of BRI1 and BAK1.
AB - BRI1 and BAK1 are Receptor-Like Kinases (RLKs), one of the largest gene families
in plants participating in various cell signal transduction from cell surface to
cytoplasm with oligomerization and phosphorylation to regulate plant growth,
development, immunity, and environmental responses. Based on the recent
investigations on the BRI1 and BAK1 and other RLKs involving in the receptor
complex formation, transphosphorylation, phosphorylation sites identification,
downstream substrates identification, and so on, it is recovered that the
receptors oligomerization and phosphorylation integrate multiple distinct
signaling to realize signaling modulation, divergence, convergence, and
specificity. The studies of the complex formation and phosphorylation of BRI1 and
BAK1 uncovered the potential signaling transduction interface primarily composed
of the RLKs. The general novel model will be helpful to understand the plant cell
signal transduction networks.
PMID- 28413948
TI - Some Remarks on Prediction of Drug-Target Interaction with Network Models.
AB - System-level understanding of the relationships between drugs and targets is very
important for enhancing drug research, especially for drug function
repositioning. The experimental methods used to determine drug-target
interactions are usually time-consuming, tedious and expensive, and sometimes
lack reproducibility. Thus, it is highly desired to develop computational methods
for efficiently and effectively analyzing and detecting new drug-target
interaction pairs. With the explosive growth of different types of omics data,
such as genome, pharmacology, phenotypic, and other kinds of molecular networks,
numerous computational approaches have been developed to predict Drug-Target
Interactions (DTI). In this review, we make a survey on the recent advances in
predicting drug-target interaction with network-based models from the following
aspects: i) Available public data sources and benchmark datasets; ii) Drug/target
similarity metrics; iii) Network construction; iv) Common network algorithms; v)
Performance comparison of existing network-based DTI predictors.
PMID- 28413949
TI - The Intrinsic Relationship Between Structure and Function of the
Sialyltransferase ST8Sia Family Members.
AB - As a subset of glycosyltransferases, the family of sialyltransferases catalyze
transfer of sialic acid (Sia) residues to terminal non-reducing positions on
oligosaccharide chains of glycoproteins and glycolipids, utilizing CMP-Neu5Ac as
the activated sugar nucleotide donor. In the four known sialyltransferase
families (ST3Gal, ST6Gal, ST6GalNAc and ST8Sia), the ST8Sia family catalyzes
synthesis of alpha2, 8-linked sialic/polysialic acid (polySia) chains according
to their acceptor specificity. We have determined the 3D structural models of the
ST8Sia family members, designated ST8Sia I (1), II(2), IV(4), V(5), and VI(6)
using the Phyre2 server. Accuracy of these predicted models are based on the
ST8Sia III crystal structure as the calculated template. The common structural
features of these models are: (1) Their parallel templates and disulfide bonds
are buried within the enzymes and are predominately surrounded by helices; (2)
The anti-parallel beta-sheets are located at the N-terminal region of the
enzymes; (3) The mono-sialytransferases (mono-STs), ST8Sia I and ST8Sia VI,
contain only a single pair of disulfide bonds, and there are no anti-parallel
beta-sheets in ST8Sia VI; (4) The Nterminal region of all of the mono-STs are
located some distant away from their core structure; (5) These conformational
features show that the 3D structures of the mono-STs are less compact than the
two polySTs, ST8Sia II and ST8Sia IV, and the oligo-ST, ST8Sia III. These
structural features relate to the catalytic specificity of the monoSTs; (6) In
contrast, the more compact structural features of ST8Sia II, ST8Sia IV and ST8Sia
III relate to their ability to catalyze the processive synthesis of oligo-
(ST8Sia III) and polySia chains (ST8Sia II & ST8Sia IV); (7) Although ST8Sia II,
III and IV have similar conformations in their corresponding
polysialyltransferase domain (PSTD) and polybasic region (PBR) motifs, the
structure of ST8Sia III is less compact than ST8Sia II and ST8Sia IV, and the
amino acid components of the several three-residue-loops in the two motifs of
ST8Sia III are different from that in ST8Sia II and ST8Sia IV. This is likely the
structural basis for why ST8Sia III is an oligoST and not able to polysialylate
and; (8) In contrast, essentially all amino acids within the threeresidue- loops
in the PSTD of ST8Sia II and ST8Sia IV are highly conserved, and many amino acids
in the loops and the helices of these two motifs are critical for NCAM
polysialylation, as determined by mutational analysis and confirmed by our recent
NMR results. In summary, these new findings provide further insights into the
molecular mechanisms underlying polyST-NCAM recognition, polySTpolySia/ oligoSia
interactions, and polysialylation of NCAM.
PMID- 28413950
TI - A Critical Review of Validation, Blind Testing, and Real- World Use of Alchemical
Protein-Ligand Binding Free Energy Calculations.
AB - Protein-ligand binding is among the most fundamental phenomena underlying all
molecular biology, and a greater ability to more accurately and robustly predict
the binding free energy of a small molecule ligand for its cognate protein is
expected to have vast consequences for improving the efficiency of pharmaceutical
drug discovery. We briefly reviewed a number of scientific and technical advances
that have enabled alchemical free energy calculations to recently emerge as a
preferred approach, and critically considered proper validation and effective use
of these techniques. In particular, we characterized a selection bias effect
which may be important in prospective free energy calculations, and introduced a
strategy to improve the accuracy of the free energy predictions.
PMID- 28413951
TI - An Unprecedented Revolution in Medicinal Chemistry Driven by the Progress of
Biological Science.
AB - The eternal or ultimate goal of medicinal chemistry is to find most effective
ways to treat various diseases and extend human beings' life as long as possible.
Human being is a biological entity. To realize such an ultimate goal, the inputs
or breakthroughs from the advances in biological science are no doubt most
important that may even drive medicinal science into a revolution. In this review
article, we are to address this from several different angles.
PMID- 28413952
TI - Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where
Molecular Modeling Meets Systems Biology.
AB - Cellular drug targets exist within networked function-generating systems whose
constituent molecular species undergo dynamic interdependent non-equilibrium
state transitions in response to specific perturbations (i.e.. inputs). Cellular
phenotypic behaviors are manifested through the integrated behaviors of such
networks. However, in vitro data are frequently measured and/or interpreted with
empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs
Haldane) relevant to isolated target populations. We propose that cells act as
analog computers, "solving" sets of coupled "molecular differential equations"
(i.e. represented by populations of interacting species)via "integration" of the
dynamic state probability distributions among those populations. Disconnects
between biochemical and functional/phenotypic assays (cellular/in vivo) may arise
with targetcontaining systems that operate far from equilibrium, and/or when
coupled contributions (including target-cognate partner binding and drug
pharmacokinetics) are neglected in the analysis of biochemical results. The
transformation of drug discovery from a trial-and-error endeavor to one based on
reliable design criteria depends on improved understanding of the dynamic
mechanisms powering cellular function/dysfunction at the systems level. Here, we
address the general mechanisms of molecular and cellular function and
pharmacological modulation thereof. We outline a first principles theory on the
mechanisms by which free energy is stored and transduced into biological
function, and by which biological function is modulated by drug-target binding.
We propose that cellular function depends on dynamic counter-balanced molecular
systems necessitated by the exponential behavior of molecular state transitions
under non-equilibrium conditions, including positive versus negative mass action
kinetics and solute-induced perturbations to the hydrogen bonds of solvating
water versus kT.
PMID- 28413953
TI - Calculating Water Thermodynamics in the Binding Site of Proteins - Applications
of WaterMap to Drug Discovery.
AB - The ability to accurately characterize the solvation properties (water locations
and thermodynamics) of biomolecules is of great importance to drug discovery.
While crystallography, NMR, and other experimental techniques can assist in
determining the structure of water networks in proteins and protein-ligand
complexes, most water molecules are not fully resolved and accurately placed.
Furthermore, understanding the energetic effects of solvation and desolvation on
binding requires an analysis of the thermodynamic properties of solvent involved
in the interaction between ligands and proteins. WaterMap is a molecular dynamics
based computational method that uses statistical mechanics to describe the
thermodynamic properties (entropy, enthalpy, and free energy) of water molecules
at the surface of proteins. This method can be used to assess the solvent
contributions to ligand binding affinity and to guide lead optimization. In this
review, we provide a comprehensive summary of published uses of WaterMap,
including applications to lead optimization, virtual screening, selectivity
analysis, ligand pose prediction, and druggability assessment.
PMID- 28413954
TI - Computational Models for Understanding of Structure, Function and Pharmacology of
the Cardiac Potassium Channel Kv11.1 (hERG).
AB - The rapid delayed rectifier current IKr is one of the major K+ currents involved
in repolarization of the human cardiac action potential. Various inherited or
drug-induced forms of the long QT syndrome (LQTS) in humans are linked to
functional and structural modifications in the IKr conducting channels. IKr is
carried by the potassium channel Kv11.1 encoded by the gene KCNH2 (commonly
referred to as human ether-a-go-go-related gene or hERG) [1, 2]. The first
necessary step for predicting emergent drug effects on the heart is determining
and modeling the binding thermodynamics and kinetics of primary and major off
target drug interactions with subcellular targets. The bulk of drugs that target
hERG channels are known to have complex interactions at the atomic scale.
Accordingly, one of the goals for this review is to provide comprehensive guide
in the universe of computational models aiming to refine our understanding of
structure-function relations in Kv11.1 and its isoforms. The special emphasis is
placed on the mapping of drug binding sites and tentative mechanisms of channel
inhibition and activation by drugs. An overview over recent structural models and
mapping of binding sites for blockers and activators of IKr current along with
the discussion on agreements and discrepancies among different models is
presented. There is an apparent reciprocity or feedback loop between drug binding
and action potential of the cardiac myocytes. Thus one has to connect drug
binding to a particular receptor so that its functional consequences impact on
the action potential duration. The natural pathway is to develop multi-scale
models that connect between receptor and cellular scales. The potential for such
multi-scale model development is discussed through the lens of common gating
models. Accordingly, the second part of this review covers an ongoing development
of the kinetic models of gating transitions and cardiac ion currents carried by
hERG channels with and without drug bound.
PMID- 28413955
TI - Drug Discovery and Molecular Dynamics: Methods, Applications and Perspective
Beyond the Second Timescale.
AB - Bio-molecular dynamics (MD) simulations based on graphical processing units
(GPUs) were first released to the public in the early 2009 with the code ACEMD.
Almost 8 years after, applications now encompass a broad range of molecular
studies, while throughput improvements have opened the way to millisecond
sampling timescales. Based on an extrapolation of the amount of sampling in
published literature, the second timescale will be reached by the year 2022, and
therefore we predict that molecular dynamics is going to become one of the main
tools in drug discovery in both academia and industry. Here, we review successful
applications in the drug discovery domain developed over these recent years of
GPU-based MD. We also retrospectively analyse limitations that have been overcome
over the years and give a perspective on challenges that remain to be addressed.
PMID- 28413956
TI - Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin.
AB - BACKGROUND: Haspin (haploid germ cell-specific nuclear protein kinase) is an
atypical serine/threonine-protein kinase that was for a long time considered an
inactive pseudokinase due to low degree of structural homology of Haspin with the
'classical' protein kinases. However, the discovery of Haspin-catalyzed
phosphorylation of histone H3 at Thr3 residue unveiled importance of Haspin in
mitosis and provided yet another link between mitotic phosphorylation pathways
and chromatin modifications. RESULTS: In this review of 111 publications, we have
(1) briefly summarized catalytic properties and physiological roles of Haspin,
(2) focussed on the architecture of Haspin and mechanisms behind its substrate
recognition, (3) provided detailed insight into the advances in the development
and characterization of Haspin-selective inhibitors, and (4) given overview of
inhibitor scaffolds that despite targeting other protein kinases feature Haspin
as a common off-target. CONCLUSION: The chemical space of Haspin-targeting low
molecular-weight-compounds has not yet been widely explored, but several
scaffolds (e.g., derivatives of acridine, beta-carboline or 5-iodotubercidin)
have emerged as promising inhibitors. The inclusion of Haspin into protein kinase
panels for profiling of low-molecular-weight-compounds in several recent studies
has provided valuable information about the structure-affinity or structure
activity relationship of well-known or novel inhibitors towards Haspin.
PMID- 28413957
TI - Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell
Lines.
AB - BACKGROUND: The possible use of acridines as anticancer agents was first
considered in the 1920's. Since then, a large number of acridine drugs have been
tested as antitumour agents, including compounds containing sulphur on the
acridine chromophore. In this review, we will discuss recent studies which have
investigated the anticancer activity of this class of acridine derivatives.
METHODS: We present the results both of our own decade-long research and also of
existing research literature into the anticancer activity of acridine derivatives
containing sulphur. The evidence of specific tumor-cell killing properties
displayed by these compounds suggest the potential of using such molecules as
anticancer therapeutics. RESULTS: During the last decade, a number of acridine
analogs have been developed by modifying the position and the nature of the
substituent on the acridine core. In this paper, we published results on the
anticancer activity of acridine derivatives containing sulfur (acridine
thioureas, acridine thiazolidine/thiazoidinone, and acridine thiosemicarbazones/
thiosemicarbazides). In cancer chemotherapy, the mechanism of the drugs is
complex, although the study of the anticancer activity of acridines has yielded
exciting results. CONCLUSION: In this review we have summarized recent literature
on the anticancer activity of acridine derivatives containing sulfur. A
considerable amount of published data suggests that these compounds exhibit
promising anticancer activity against selected cancer cell lines. The obtained
results can be helpful in the development of new pharmaceutical agents.
PMID- 28413958
TI - Anti-fatigue effects of active ingredients from traditional Chinese medicine: a
review.
AB - Fatigue, a phenomenon which is believed to be caused by body exercise, can lead
to the failure of predetermined exercise intensity maintenance and sport ability
declination. The usage of traditional Chinese medicine (TCM) in the treatment of
fatigue has long been practiced in clinical and showed significant effects. This
article covers related literatures in recent years and sorts the effective
ingredients from TCM for treating fatigue into a few categories including
alkaloids, saponins, polysaccharides, polyphenols, polypeptide, terpene, proteins
and other active ingredients. Research status, sources, models, efficacy and
mechanisms of active ingredients and their monomer in the treatment of fatigue
are discussed. Pharmacological research shows that active ingredients of
polysaccharide can significantly improve body's resistance through promoting
glycogen synthesis, reducing sports metabolites and increasing hypoxia tolerance;
Alkaloids has been proved to be effective in promoting the reserving of various
glucogen substances, improving exercise endurance and speeding up the metabolism
of body's urea nitrogen in mice; With the increase of glycosides amount, up goes
the sport endurance, liver glycogen content and the ability of clear lactate
index in mice, indicating that saponin has clear, dose-dependent anti-fatigue
effect; Polyphenols also have functions of resisting fatigue, where they reduce
free radicals accumulated and thus slow down the rapid declination of exercise
capacity when doing sports; There are other active ingredients of TCM that have
biological activities, like some proteins, anthraquinones, terpenes, unsaturated
fatty acid monomer compounds; And research has found that tonic medicine can
promote the elimination of fatigue and improve athletic ability.
PMID- 28413959
TI - Chemopreventive Properties of Tolfenamic Acid: A Mechanistic Review.
AB - Tolfenamic acid is one of the conventional non-steroidal anti-inflammatory drugs
(NSAIDs) commonly used for the treatment of inflammation, migraines and pain.
There has been a growing body of experimental evidence that tolfenamic acid
possesses anti-cancer activity. However, in order to develop a therapeutic
strategy using tolfenamic acid for the treatment of cancer, further research is
required to highlight reliable cellular and molecular mechanisms of anti-cancer
properties. Tolfenamic acid has been shown to alter the expression of several
genes that represent cancer hallmarks including apoptosis, growth arrest,
angiogenesis and metastasis. Recently, a couple of research groups including ours
reported that tolfenamic acid targets multiple oncogenic or tumor suppressive
signaling pathways in various types of cancer models. Here, we highlight multiple
molecular targets responsible for the anti-cancer mechanism of tolfenamic acid
and the benefits of combinational use of this drug with other anti-cancer drugs.
PMID- 28413960
TI - Circulating ACE2 in Cardiovascular and Kidney Diseases.
AB - Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the
conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti
fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2
counterbalances the effects of Ang II, it has been proposed as a biomarker in
kidney disease patients. Circulating ACE2 has been studied in human and
experimental studies under physiological and pathological conditions and
different techniques have been assessed to determine its enzymatic activity. In
patients with cardiovascular (CV) disease circulating ACE2 has been shown to be
increased. In addition, hypertensive and diabetic patients have also shown higher
circulating ACE2 activities. A study in type 1 diabetes patients found a negative
association between circulating ACE2 and estimated glomerular filtration rate in
male and female patients. Recently, it has been demonstrated that circulating
ACE2 is increased in male patients with chronic kidney disease (CKD) and that it
is independently associated with other classical CV risk factors, such as
advanced age and diabetes. Furthermore, circulating ACE2 has been shown to be
associated with silent atherosclerosis and CV outcomes in CKD patients. In
diabetic nephropathy, experimental studies have demonstrated an increase in
circulating ACE2 activity both at early and late stages of the disease, as well
as a direct association with increased urinary albumin excretion, suggesting that
it may be increased as a renoprotective mechanism in these patients. In this
paper we will review the measurement of circulating ACE2 and its role in kidney
disease, as well as its potential role as a renal and CV biomarker.
PMID- 28413961
TI - Incretins and Lipid Metabolism.
AB - BACKGROUND: Recent findings indicate that incretin hormones and incretin-based
therapies may affect the metabolism of lipoproteins, although the corresponding
mechanisms are not clearly defined. OBJECTIVE: To summarize the available data on
the mechanisms linking incretins with the characteristics of serum lipoproteins
and discuss the clinical implications of these relationships. METHODS: PubMed was
searched using the terms "incretins", "GLP-1", "GIP" and "lipids",
"dyslipidemia", "triglycerides", "apolipoprotein B48". All articles published in
the English language until June 2016 were assessed and the relevant information
is presented here. RESULTS: GLP-1, and therapies that increase its activity,
exert a beneficial effect on lipoprotein metabolism that is translated in a
reduction in the fasting and postprandial concentration of triglycerides and a
small improvement in the concentration and function of HDLs. In addition, a shift
towards larger, less atherogenic particles usually follows the administration of
GLP-1 receptor agonists. The mechanisms that underlie these changes involve a
direct effect of GLP- 1 on the hepatic and intestinal production of triglyceride
rich lipoproteins, the GLP-1 induced increase in the production and function of
insulin, the activation of specific areas of central nervous system as well as
the increase in the peripheral utilization of triglycerides for energy
production. On the other hand, GLP-2 increases the absorption of dietary fat and
the production of triglyceride-rich lipoproteins while the role of GIP on lipid
metabolism remains indeterminate. CONCLUSION: GLP-1 and incretin-based therapies
favorably affect lipid metabolism. These effects may contribute to the beneficial
effects of incretin-based therapies on atherosclerosis and fatty liver disease.
PMID- 28413963
TI - Overview of Cantharidin and its Analogues.
AB - BACKGROUND: Cantharidin has been categorized as highly toxicant in Chinese
medicine. But cantharidin can efficiently treat different types of diseases, such
as molluscum contagiosum. While cantharidin is quite useful, unfortunately, due
to its side effects, increasing regulations have limited access to this useful
therapeutic option. Cantharidin's toxic effects have caused it to fall into
disuse for most legitimate medical purposes. Although cantharidin generates
effects and its advantages must be realized. Recently, cancer affects people's
life more and more. Because cantharidin can treat some cancers, so solutions must
be used to reduce side effects. This review aims to describe some its analogues,
several efficient methods to inhibit the side effects of cantharidin and
pharmacogenomics of cantharidin. METHODS: We searched for research about
cantharidin by entering the database. Then evaluated these papers and analyzed
their founding, solution, mechanism, etc., and targeted to screen the papers
related to the content of our research, and then sorted them out in accordance
with the solution, mechanism research and other content. Finally, these content
was unified into a framework. RESULTS: Some cantharidin's analogues were found
that they show some similar functions to cantharidin and we found that
norcantharidin, acylthiourea derivatives, cantharidinamides, anhydride-modified
derivatives and other derivatives have less side effects. The modified
cantharidin analogues reduce toxicity in hepatocytes. Cantharidin consists of a
six-ring and a five-ring, the moiety of oxygen on the six-ring and the anhydride
section exhibit biochemical activity. Protein phosphatases are associated with
many cellular processes including apoptosis, cell cycle progression and so on.
Cantharidin can cause apoptosis and double-stand breakage of DNA. Cantharidin and
norcantharidin can efficiently inhibit the activity of mammalian and plant
protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) in vivo.
Cantharidin inhibits PP5 at the nanomolar level with an IC50 value of 600 nM. PP5
can manage the cellular survival, death, proliferation and other some
intracellular biological activities in mammals. After cantharidin's treatment,
the level of EtPP5 mRNA expression was downregulated. Their also can be used to
inhibit the Glutathione S-transferases (GSTs), angiogenesis and the expression of
A549 human lung cancer cells, trigger eryptosis and induced bladder cancer cell
apoptosis. We found that using Vitamin C and ginsenosides and translating
cantharidin into nanoparticles can minimize the cantharidin side effects in the
patients. CONCLUSION: Cantharidin can inhibit various tumor cell lines.
Cantharidin causes both DNA single- and double- strand breaks and induces
apoptosis. Although cantharidin shows some toxicity for human, its anti-cancer
effects should be taken seriously. Several viable methods can help solve this
problem. The most important pharmacogenomics of cantharidin is that cantharidin
can inhibit PPs, because PPs are associated with many cellular processes. This
prospect is very broad and needs to continue studying.
PMID- 28413964
TI - Sex-Genetic Interaction in the Risk for Cerebrovascular Disease.
AB - Cerebrovascular disease (CeVD) is one of the major causes of death and a leading
cause of disability worldwide. CeVD is a complex and multifactorial disease
caused by the interaction of environment and genetic factors. Women have lower
CeVD incidence than men until an advanced age, when the incidence of CeVD rises
dramatically in women. Therefore, sex has been validated as an important risk
factor in the etiology of CeVD, especially ischemic stroke. Although the
importance of sex steroids have been heavily studied in the mechanism of neuronal
injury, the experimental and clinical data suggest that hormones do not fully
account for male versus female CeVD patterns. Sex-specific genetic processes have
been implicated in the different rate of risk for atherosclerosis and CeVD. In
this review, we discuss sex-specific CeVD processes, describe the hormonal impact
on the risk for CeVD, the results from studies in transgenic animals, and from
human genetic studies. Moreover, heritability of ischemic stroke in women and men
as well as identification of possible sex-specific biomarkers for CeVD are
discussed. Understanding the complex interactions between hormonal and genetic
mechanisms in the CeVD risk will allow for new sex-specific approaches in disease
treatment and prevention in clinical practice.
PMID- 28413965
TI - Small Molecule Drugs and Targeted Therapy for Melanoma: Current Strategies and
Future Directions.
AB - Malignant melanoma is the most aggressive and life-threatening skin cancer.
Melanoma develops in melanocytes and is characterized by a very high tendency to
spread to other parts of the body. Its pathogenesis depends on DNA mutations
leading to the activation of oncogenes or to the inactivation of suppressor
genes. The identification of misregulations in intracellular signal transduction
pathways has provided an opportunity for the development of mutation-specific
inhibitors, which specifically target the mutated signaling cascades. Over the
last few years, clinical trials with MAPK pathway inhibitors have shown
significant clinical activity in melanoma; however, their efficacy is limited due
to the onset of acquired resistance. This has prompted a large set of preclinical
studies looking at new approaches of pathway- or target-specific inhibitors. This
review gives an overview of the latest developments of small molecule targeting
multiple molecular pathways in both preclinical and clinical melanoma settings,
with particular emphasis on additional strategies to tackle the reduced
responsiveness to inhibitor treatment as possible future directions.
PMID- 28413966
TI - The Clinical Problems of Hypertension Treatment in Hemodialysis Patients.
AB - Hypertension (HT) is present in more than 80% of patients undergoing Hemodialysis
(HD). Elevated Blood Pressure (BP) in hemodialysis patients is associated with
cardiovascular events and mortality only when BP is recorded with home or
ambulatory monitoring, since pre- and post-dialysis measurements are not valid
estimates of BP levels during the interdialytic interval. Sodium and water
overload is the most important of several mechanisms involved in HT development
in HD. In this context, non-pharmacologic measures to ensure water and sodium
balance by achieving patient dry weight and decreasing daily sodium intake,
through modification of sodium level in the diet or in dialysis dialysate, are
fundamental for HT control. After these strategies are properly implemented, the
introduction of drug treatment can further help in achieving optimum BP. All
major antihypertensive classes, with the exception of diuretics, can be
considered in HT management, as current evidence suggest that the use of agents
from these classes was associated with reduced cardiovascular risk. The choice of
a specific antihypertensive drug should be based on the co-morbid conditions of
the patient, and the pharmacologic characteristics of the agent, including
dialyzability. Of note, the need of increasing the number of antihypertensive
drugs, should be each time balanced against reappraisal of the non-pharmacologic
measures, as increased antihypertensive efficacy can result in a vicious circle
of more difficulties regarding dry weight reduction, possible volume overload,
and further BP increase.
PMID- 28413962
TI - Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic
Communication, and Pharmacological Relevance.
AB - BACKGROUND: Knowledge of molecular marker (typically protein or mRNA) expression
in neural systems can provide insight to the chemical blueprint of signal
processing and transmission, assist in tracking developmental or pathological
progressions, and yield key information regarding potential medicinal targets.
These markers are particularly relevant in the mammalian brain in the light of
its unsurpassed cellular diversity. Accordingly, molecular expression profiling
is rapidly becoming a major approach to classify neuron types. Despite a
profusion of research, however, the biological functions of molecular markers
commonly used to distinguish neuron types remain incompletely understood.
Furthermore, most molecular markers of mammalian neuron types are also present in
other organs, therefore complicating considerations of their potential
pharmacological interactions. OBJECTIVE: Here, we survey 15 prominent
neurochemical markers from five categories, namely membrane transporters, calcium
binding proteins, neuropeptides, receptors, and extracellular matrix proteins,
explaining their relation and relevance to synaptic communication. METHOD: For
each marker, we summarize fundamental structural features, cellular
functionality, distributions within and outside the brain, as well as known drug
effectors and mechanisms of action. CONCLUSION: This essential primer thus links
together the cellular complexity of the brain, the chemical properties of key
molecular players in neurotransmission, and possible biomedical opportunities.
PMID- 28413967
TI - Uncontrolled Hypertension and Oncology: Clinical Tips.
AB - INTRODUCTION: Angiogenesis is fundamental for tumour development and progression.
Thus, anti-angiogenic agents have been developed and are mainly vascular
endothelial growth factor (VEGF) pathway inhibitors. However, these agents
commonly exhibit cardiac and renal toxicity, proteinuria and hypertension (HT).
In fact, with the use of anti-angiogenic agents a rapid dose-dependent increase
of blood pressure (BP) is observed. The possible mechanisms of VEGF inhibitors
induced HT include systemic endothelial dysfunction, renal impairment as well as
vascular micro- and macroangiopathy. Furthermore, the simultaneous use of non
steroidal anti-inflammatory drugs (NSAIDs) and opioids in these patients results
in uncontrolled HT. CONCLUSION: Lifestyle changes are the cornerstone of
antihypertensive treatment. No clear recommendations for a specific
antihypertensive agent can be made. In most cases antihypertensive management
needs to be individualized to each patient. Calcium channel blockers (CCBs) are
considered as first line option, while renin-angiotensin-aldosterone system
(RAAS) blockers should be the agents of choice in patients with proteinuria.
Centrally acting antihypertensive agents and diuretics can also be used. Careful
monitoring is critical during therapy and BP should be assessed every week and
before any new cycle or infusion of anti-VEGF therapy. If BP remains uncontrolled
anti-VEGF treatment discontinuation should be considered. Withdrawal of anti-VEGF
therapy needs also a re-evaluation of antihypertensive therapy since BP will
return to the prior baseline levels.
PMID- 28413968
TI - Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the
Dots.
AB - INTRODUCTION: Heart failure (HF) with preserved ejection fraction (EF) (HFpEF)
accounts for approximately 50% of HF cases and its prevalence relative to HF with
reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF
patients and it is implicated in both the pathogenesis and the prognosis of the
disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We
reviewed the literature for epidemiologic data supporting the co-aggregation of
the two entities as well as patho-physiologic mechanisms linking HT to HFpEF.
Most importantly, we focused on treatment options targeting HT as a preventive
strategy for delaying the progression of diastolic dysfunction or decreasing the
odds for developing HFpEF. CONCLUSION: Along this line, we summarized the
evidence and efficacy associated with different classes of antihypertensive
medications in HFpEF patients. Finally, non-pharmacological approaches, including
renal denervation and lifestyle modifications, to achieve optimal blood pressure
(BP) control in HFpEF patients are reported. Unfortunately, no specific
antihypertensive treatment has established a major survival benefit in this high
risk subjects. Until the results of the efficacy of the novel drug LCZ696
(valsartan/ sacubitril) are available, the continuous monitoring and lowering of
the BP by pharmacological and non-pharmacological means should be considered the
major preventive and treatment strategy in HFpEF patients.
PMID- 28413970
TI - Optimizing the Management of Uncontrolled/Resistant Hypertension. The Importance
of Sleep Apnoea Syndrome.
AB - INTRODUCTION: Obstructive Sleep Apnoea (OSA) constitutes the most prevalent form
of abnormal respiratory control during sleep in adults. Evidence linked OSA to
cardiovascular disease, and the role of OSA in abnormal Blood Pressure (BP)
control has been extensively studied. Although longitudinal trials suggest a
causative role of OSA in the development of hypertension, the evidence is not
fully consistent. Nasal continuous positive airway pressure (nCPAP) applied
during sleep is well documented and a highly efficient therapeutic aid to
eliminate OSA. It has been repeatedly shown that nCPAP-therapy is also associated
with modest BP lowering effect in hypertensive OSA-patients, and the magnitude of
the observed effect correlates with the severity of OSA. However, it is unlikely
that nCPAP would normalize BP. CONCLUSION: There are few studies which tested the
interplay between OSA, nCPAP and certain BPlowering drug classes. Angiotensin
receptor blockers may show synergistic hypotensive effect with nCPAP, whereas
mineralocorticoid receptor blocker has been shown to modestly attenuate the
severity of OSA. Additionally, the application of chronotherapy may be of special
use in such patients. The current evidence is sufficient to promote persistent
and effective nCPAP-therapy as a standard in all eligible OSA-patients with
difficult-to-control hypertension.
PMID- 28413969
TI - Optimizing the Management of Uncontrolled Hypertension: What do Triple Fixed-Dose
Drug Combinations Add?
AB - Fixed-dose triple drug combinations represent one of the latest innovations of
pharmacotherapy for hypertension (HT). They combine a traditional renin
angiotensin system blocker, a diuretic and a calcium channel blocker. The main
benefit is the simplification of treatment regimen because 3 different agents are
combined at different doses in a single pill. Improving adherence to treatment
partly explains why this kind of combination may effectively reduce blood
pressure (BP). BP lowering by a single- pill triple-drug combination can be
approximately predicted, by using appropriate formulas described in previous meta
analysis of randomized trials. Thus, clinicians may select the appropriate dose
for each of the combined drugs. Selection of different types of fixed-dose triple
drug combinations relies upon clinical experience, commercial availability and
evidence from clinical trials and metaanalyses for each agent alone. However,
triple fixed-dose drug combinations should be reserved only for patients with
uncontrolled BP with 2 agents, poor adherence in complex therapeutic regimens or
on inappropriate free-drug combinations. Also, triple therapy may help overcome
clinical inertia by prescribing more potent antihypertensive formulations in one
pill. In contrast, this type of multiple-drug fixed-dose combination might be
less safe in very old and frail patients, as well as in those with chronic kidney
disease. Although new combinations may help overcome the clinical inertia of
achieving individualized BP targets, doctors should also pay attention
reinforcement of lifestyle changes.
PMID- 28413971
TI - Structure of C-terminal Domain of Peptidyl-prolyl cis-trans Isomerase from
Pseudomonas syringae pv. Tomato str. DC3000 at 1.6A Resolution.
AB - BACKGROUND: Peptidyl-prolyl cis-trans isomerase (PPIase) accelerates the
intrinsically slow conversion between cis- and trans- configurations of proline,
thus affecting backbone conformation and altering the direction of peptide
chains. PPIase from Pseudomonas syringae pv. Tomato (PSPTO) DC3000 (PSPTO-PPIase)
is considered to belong to the FKBP subfamily of PPIase. OBJECTIVE: To solve the
high resolution structure of the PSPTO-PPIase, and to explore its potential
function in plants pathogen PSPTO DC3000. METHOD: The PSPTO-PPIase was expressed
in E.coli and purified through ion exchange and size exclusion chromatography.
While only the C-terminal domain of PSPTO-PPIase was successfully crystalized,
and its structure was solved to 1.6 A resolution by molecular replacement method.
RESULTS: Structural comparison showed that PSPTO-PPIase adopts a similar overall
fold with microphage infectivity potentiators (MIPs), which also belong to the
FKBP subfamily of PPIase. In addition, the BIAcore result confirmed that PSPTO
PPIase can bind an immunosuppressive drug FK506 as some other FKBP subfamily
members do. CONCLUSION: Our results suggested that PSPTO-PPIase may function in a
similar manner to virulent factor MIPs during pathogenesis. And the
immunosuppressive drugs FK506 and rapamycin binding to PSPTO-PPIase potentially
interferes and inhibits the plant pathogen PSPTO DC3000. In addition, the amino
acids with short side chains in the fourth loop (L4) of PSPTO-PPIase may account
for its variable roles in the respective pathogen.
PMID- 28413972
TI - Xanthine Oxidase and its Role as Target in Cardiovascular Disease: Cardiovascular
Protection by Enzyme Inhibition?
AB - BACKGROUND: Formerly, hyperuricemia was mainly restricted to the rich population,
but now-a-days it is a condition affecting wide parts of western civilization.
Although only a minority of our population develops clinically relevant
symptomatic hyperuricemia, there is growing evidence that elevated serum uric
acid levels might be associated with elevated cardiovascular risk and
cardiovascular disease progression. But it is not clear whether uric acid is just
a biomarker or exerts detrimental effects itself. The xanthine oxidoreductase
(XOR) is an essential enzyme for the generation of uric acid. A typical
pharmacological therapy to reduce the uric acid amounts is inhibition of XOR.
There is good evidence that inhibition of uric acid reduces cardiovascular events
in patients. The question arises if XOR inhibition might be an attractive target
to reduce cardiovascular events in patients with high or even normal uric acid
levels. METHOD: This review summarizes the available publications on the
relationship between XOR and cardiovascular co-morbidities. RESULTS: The
association of elevated serum uric acid level with oxidative damage in the vessel
wall, inflammatory and proliferative vascular changes, hypertension and impaired
kidney function are depicted. In addition, the therapeutics currently approved
for the treatments of hyperuricemia are outlined and an overview regarding novel,
currently researched XOR inhibitors is provided. CONCLUSION: Observational and
small prospective studies already have given hints for positive cardiovascular
effects of XOR inhibition. However, larger prospective studies investigating
cardiovascular outcomes are awaited to validate the potential beneficial effect
of XOR inhibition for reduction of the cardiovascular burden.
PMID- 28413973
TI - Docking-Related Survey on Natural-Product-Based New Monoamine Oxidase Inhibitors
and Their Therapeutic Potential.
AB - BACKGROUND: This is an exciting period for research on monoamine oxidase and its
effects on central nervous system. As the current hitting-one-target, therapeutic
strategy has become quite inefficient for the treatment of various neurological
disorders Objective: The objective of this review is to identify and critically
discuss the computational development of multi-target natural and related ligand
MAO protein docking approaches in the study of monoamine oxidase (MAO) enzymes.
DISCUSSION: Computational development of the new compounds from natural and
related synthetic origin, active as MAO inhibitors (MAOIs) was discussed in some
detail. The docking studies related to the alkaloids and their various categories
secondary metabolites from plants like alkaloids, flavonoids and xanthones class
of compounds specially caffeine, beta-carboline, naphthoquinone, morpholine,
piperine, amphetamine and furthermore curcumin, eugenol, trans-Farnesol and many
other extracted plant constituents with their docking studies were discussed in
detail. CONCLUSION: It is apparent that, by this computational docking approach,
more selective, reversible and potent molecules could be proposed as MAO
inhibitors by precise modifications on the basic scaffold.
PMID- 28413974
TI - Identification of Cell Cycle-Regulated Genes by Convolutional Neural Network.
AB - BACKGROUND: The cell cycle-regulated genes express periodically with the cell
cycle stages, and the identification and study of these genes can provide a deep
understanding of the cell cycle process. Large false positives and low overlaps
are big problems in cell cycle-regulated gene detection. METHODS: Here, a
computational framework called DLGene was proposed for cell cycle-regulated gene
detection. It is based on the convolutional neural network, a deep learning
algorithm representing raw form of data pattern without assumption of their
distribution. First, the expression data was transformed to categorical state
data to denote the changing state of gene expression, and four different
expression patterns were revealed for the reported cell cycle-regulated genes.
Then, DLGene was applied to discriminate the non-cell cycle gene and the four
subtypes of cell cycle genes. Its performances were compared with six traditional
machine learning methods. At last, the biological functions of representative
cell cycle genes for each subtype are analyzed. RESULTS: Our method showed better
and more balanced performance of sensitivity and specificity comparing to other
machine learning algorithms. The cell cycle genes had very different expression
pattern with non-cell cycle genes and among the cell-cycle genes, there were four
subtypes. Our method not only detects the cell cycle genes, but also describes
its expression pattern, such as when its highest expression level is reached and
how it changes with time. For each type, we analyzed the biological functions of
the representative genes and such results provided novel insight to the cell
cycle mechanisms.
PMID- 28413975
TI - The Safety of Ovarian Preservation in Stage I Endometrial Endometrioid
Adenocarcinoma Based on Propensity Score Matching.
AB - BACKGROUND: Most patients with early stage endometrial endometrioid
adenocarcinoma (EEAC) are treated with hysterectomy and bilateral oophorectomy.
But this surgical menopause leads to long-term sequelae for premenopausal women,
especially for young women of childbearing age. This population-based study was
to evaluate the safety of ovarian preservation in young women with stage I EEAC.
METHODS: Patients of age 50 or younger with stage I EEAC were explored from the
Surveillance, Epidemiology and End Results program database during 2004 to 2013.
Propensity score matching was used to randomize the data set and reduce the
selection biases of doctors. Univariate analysis and multivariate cox
proportional hazards model were utilized to estimate the safety of ovarian
preservation. RESULTS: A total of 7183 patients were identified, and ovarian
preservation was performed in 863 (12 %) patients. Compared with women treated
with oophorectomy, patients with ovarian preservation significantly tend to be
younger at diagnosis (P-value < 0.001) and more likely diagnosed as stage IA
EEAC, to have better differentiated tumor tissues and smaller tumors, as well as
less likely to undergo radiation and lymphadenectomy. 863 patients treated with
oophorectomy were selected by propensity score matching. After propensity score
matching, the differences of all characteristics between ovarian preservation and
oophorectomy were not significant and potential confounders in the two groups
decreased. In univariate analysis of matched population, ovarian preservation had
no effect on overall (P-value=0.928) and cancer-specific (P-value=0.390)
mortality. In propensityadjusted multivariate analysis, ovarian preservation was
not significantly associated with overall (HR=0.69, 95%CI=0.41-1.68, P
value=0.611) and cancer-specific (HR=1.65, 95%CI=0.54-5.06, Pvalue= 0.379)
survival. CONCLUSION: Ovarian preservation is safe for young women with stage I
EEAC, which is not significantly associated with overall and cancer-specific
mortality.
PMID- 28413977
TI - New Suggestions in Sublingual Immunotherapy for House Dust Mite- Related Allergic
Diseases.
AB - BACKGROUND: The indications for Allergen immunotherapy (AIT) in patients
suffering from House Dust Mite (HDM)-related allergic diseases are presently
based on incomplete data. This is essentially based on the fact that HDM allergy
is difficult to evaluate in clinical trials, due to the largely variable allergen
exposure and symptoms, and to the long periods of observation needed to assess
the effects. In addition, at variance with pollen allergy, in HDM allergy asthma
is more prevalent. However, several AIT products have been approved for HDM
induced allergic rhinitis, according to their ascertained clinical efficacy,
tolerability and safety profile, particularly in the sublingual form (SLIT).
OBJECTIVE: We reviewed herein the available data on AIT in patients with HDM
induced allergic diseases, with a particular attention to the new product MK-8237
HDM-SLIT tablets, concerning its efficacy and safety profile. METHOD: In the
recent years, several randomized placebo-controlled clinical trials have been
performed in Europe, North America and Japan to evaluate the efficacy of HDM
sublingual tablets in patients with HDM-induced allergic asthma and allergic
rhinitis, mainly assessing the reduction of symptoms, exacerbations and
corticosteroid intake. RESULTS: The results of the published clinical trials were
encouraging and led to the approval and commercialization of MK-8237 HDM-SLIT
tablet. CONCLUSION: The favorable efficacy and safety profile of MK-8237 HDM-SLIT
tablets provided a consolidated therapeutic option for patients with HDM-induced
allergic rhinitis and asthma.
PMID- 28413976
TI - Laboratory Monitoring or Measurement of Direct Oral Anticoagulants (DOACs):
Advantages, Limitations and Future Challenges.
AB - BACKGROUND: The Direct Oral Anticoagulants (DOACs) represent a new generation of
antithrombotic agents, providing direct inhibition of either thrombin (factor
IIa; FIIa) or activated factor X (FXa). Around the globe, their use is
progressively rising, as these new agents replace the historical anticoagulants
(heparin and vitamin K antagonists including warfarin) for various clinical
conditions in medical practice. Other acronyms used to designate DOACs include
TSOAC (target specific oral anticoagulants) and NOAC (novel; or non-vitamin K
antagonist oral anticoagulants). Currently available DOACS include dabigatran
(FIIa inhibitor), along with rivaroxaban, apixaban, edoxaban and betrixaban (FXa
inhibitors). OBJECTIVE: This narrative review aims to briefly summarise the
evidence concerning utility of different laboratory assays for qualitative or
quantitative assessment of DOACs, emphasizing the difference between 'drug
monitoring' and 'drug measurement' and ultimately discussing advantages and
limitations of these processes. RESULTS AND CONCLUSION: Recently, the dogma that
these innovative anticoagulant agents will not necessitate laboratory testing has
been challenged with the recognition that assessment of drug concentration or
activity may be required in some circumstances, although this does not
immediately translate to the concept of 'drug monitoring'.
PMID- 28413978
TI - Advances and Challenges in Drug Design of PPARdelta Ligands.
AB - BACKGROUND: Peroxisome proliferator-activated receptors (PPAR) are nuclear
receptors activated by endogenous fatty acids and prostaglandins that are
classified into three types: alpha, gamma and delta, which have different
functions and tissue distribution. PPAR modulators have been exploited to the
treatment of important metabolic diseases, such as type 2 diabetes mellitus and
metabolic syndrome, which are considered relevant epidemic diseases currently.
Along the last decades, several studies have reported structural differences
between the three PPAR subtypes associated with the discovery of selective
ligands, dual and pan-agonists. Nowadays, there are several approved drugs that
activate PPARalpha (fibrates) and PPARgamma (glitazones), but up to now there is
none clinically used drug targeting PPARdelta. Additionally, several side-effects
associated with the use of PPARalpha and gamma agonists are reported by
regulatory agencies, which do not indicate anymore their use as first-line drugs.
OBJECTIVE: A significant new market has grown in the last years, focusing on the
development of new PPARdelta agonists as drug candidates to treat metabolic
diseases and, in this sense, this study proposes to review the structural
requirements to achieve selective PPARdelta activation, as well to discuss the
most relevant agonists in clinical trials, providing information on the current
phase in the drug discovery and design targeting PPARdelta. CONCLUSION: Several
PPARdelta ligands with high potency were reported in the literature and were
designed or discovered by a combination of experimental and computational
approaches. Furthermore, the reported importance of pockets and individual
residues at PPARdelta binding site as well as the importance of substituent and
some physicochemical properties that could help to design of new classes of
agonists.
PMID- 28413979
TI - Drug Resistance of Enzalutamide in CRPC.
AB - : Understanding and targeting the mechanisms of resistance to enzalutamide in
castration resistant prostate cancer. BACKGROUND: Enzalutamide (MDV3100, XTANDI)
is a second generation androgen receptor inhibitor that is designed for the
treatment of castration-resistant prostate cancer (CRPC) and has prolonged
survival time. The mechanisms of mdv3100 resistance have not yet been clearly
clarified and the majority of treated patients, innate or acquiring resistance
invariably arises. OBJECTIVE: The purpose of this review is to summarize the main
data available on the mechanisms of resistance to mdv3100. Understanding how the
resistance aroused may have clinical implications in underlying the usefulness of
prognostic and predictive biomarkers in daily practice and improving the
strategies. RESULTS: Resistance to MDV3100 could be basically divided into two
distinct pathways, either dependent or independent of the androgen receptor
activity. Androgen receptor (AR) axis is sitll the most important pathway for
prostate cancer cells and it is still currently regarded as a critical resistant
mechanism. CONCLUSION: Targeting these newly identified signals, especially AR
axis, could be potentially overcome through novel therapeutic agents,
synergically improve the ADT in CRPC.
PMID- 28413980
TI - Therapeutic Applications of Liposomal Based Drug Delivery and Drug Targeting for
Immune Linked Inflammatory Maladies: A Contemporary View Point.
AB - Immune-based inflammatory diseases involve immune related dysregulation in
different sites of body, which includes rheumatoid arthritis, multiple sclerosis,
inflammatory bowel disease, atherosclerosis, etc. Advancements in molecular
research have facilitated investigation of their pathogenesis that is involved in
inflammatory cytokines cells and several genes. The available drug therapy
provides suboptimal therapeutic effects and higher adverse effects. Emergence of
liposomal systems of the drugs meant for the above mentioned disease has gained
broader importance due to their high treatment efficacy by means of optimal
therapeutic drug delivery. Beyond the conventional liposomal formulations,
evolution of second generation liposomes including stealth liposomes, cationic
liposomes, immuno-liposomes, etc. has gained tremendous attention owing to their
drug target potential, diagnostic importance and imaging in treatment of above
mentioned immune mediated inflammatory disorders.
PMID- 28413981
TI - Default Mode Network Connectivity and Related White Matter Disruption in Type 2
Diabetes Mellitus Patients Concurrent with Amnestic Mild Cognitive Impairment.
AB - BACKGROUND: As a risk factor for Alzheimer's disease (AD), type 2 diabetes
mellitus (T2DM) itself causes cognitive impairment and has higher prevalence of
mild cognitive impairment (MCI). OBJECTIVE: The aim of this study was to explore
the cognition especially the episodic memory difference, the DMN functional
connectivity and DMN-related white matter integrity in patients with both T2DM
and amnestic MCI (T2DM-MCI) as compared to patients with T2DM only. METHODS:
Focusing especially on T2DM population, we investigated the default mode network
(DMN) through resting-state functional magnetic resonance imaging among 22
elderly T2DM-MCI patients and 24 elderly T2DM patients. Including primarily the
bilateral cingulum, hippocampus and uncinate fasciculus, these DMN white matter
fibers were also closely associated with episodic memory and the integrity of
them was also investigated using diffusion tensor imaging in 19 elderly T2DM-MCI
patients and 23 elderly T2DM patients. RESULTS: Compared with the patients with
T2DM, the T2DM-MCI patients performed worse in several areas of cognition besides
episodic memory, and showed stronger DMN functional connectivity in the left
precuneus and weaker functional connectivity in the left calcarine, as well as
decreased integrity of the left cingulate bundle and bilateral uncinate
fasciculus. Furthermore, a correlation analysis indicated that higher left
calcarine connectivity was associated with better episodic memory performance
among the overall group. CONCLUSION: Our results demonstrated that T2DM patients
with comorbid amnestic MCI had abnormal functional connectivity patterns and
decreased white matter integrity, which could potentially serve as AD or AD risk
biomarkers for early detection of those elderly individuals with T2DM.
PMID- 28413982
TI - Optimizing ADAS-Cog Worksheets: A Survey of Clinical Trial Rater s' Perceptions.
AB - BACKGROUND: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADASCog)
remains the most widely used test of longitudinal cognitive functioning in
Alzheimer's disease (AD) clinical trials. Unlike most neuropsychological tests,
the ADAS-Cog source documentation worksheets are not uniform across clinical
trials, and vary by document layout, inclusion of administration and/or scoring
instructions, and documentation of subtest scoring (e.g., recording correct
versus incorrect scores), among other differences. Many ADAS-Cog test
administrators (raters) participate in multiple AD trials and switching between
different ADAS-Cog worksheets may increase the likelihood of administration
and/or scoring mistakes that lessen the reliability of the instrument. An
anonymous online survey sought raters' experiences with ADAS-Cog worksheets and
their opinions on the design and content of the worksheets. RESULTS: Results of
the survey indicated preference for structure and standardization of the ADASCog
worksheets, which has been considered in the development of a standard ADAS-Cog
source document by the Alzheimer's Disease Cooperative Study (ADCS) Working
Group.
PMID- 28413983
TI - Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients Control CCL4
and CXCL10 Levels in a Human Blood Brain Barrier Model.
AB - BACKGROUND: Alzheimer's disease (AD) is accompanied by a neuroinflammation
triggering chemoattractant signals towards peripheral blood mononuclear cells
(PBMCs), which in turn could reduce amyloid plaques after transmigration through
the blood brain barrier (BBB). But the chemotactic environment remains unclear.
OBJECTIVE: To analyze five chemokines known to be involved in AD in three
different cellular models to better understand the cellular and molecular
interactions in the BBB. METHOD: Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1)
were measured in isolated cells, a BBB model without PBMCs (H4 and hCMEC/D3
cells, a neuroglioma and human endothelial cells, respectively) and in a complete
BBB model with PBMCs from AD patients at a moderate stage. In one set of
experiments, H4 cells were treated with Abeta42. RESULTS: CCL2 and CCL5
significantly increased in hCMEC/D3 and H4 cells in the complete BBB model. In
turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10
increased in all cellular actors in the complete BBB model, compared to isolated
cells. For CCL4, PBMCs induced a robust increase in H4 and hCMEC/D3. In turn, the
level of CCL4 decreased in PBMCs. Furthermore, PBMCs triggered a significant
increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of Abeta42 was observed
in the complete BBB model. CONCLUSION: These findings highlight the interest of a
BBB model in order to explore chemokine production. For the first time, results
showed that PBMCs from patients with AD can control the production of CCL4 and
CXCL10 in a human BBB model.
PMID- 28413984
TI - Prevalence of Frailty in Mild to Moderate Alzheimer's Disease: A Systematic
Review and Meta-analysis.
AB - BACKGROUND: Frailty is a state of increased vulnerability to poor resolution of
homeostasis as a consequence of age-related decreased physiological reserves.
Although physical frailty and cognitive impairment have been shown to be
associated, evidence on the prevalence of frailty in Alzheimer's disease is
scarce. OBJECTIVE: To conduct a systematic review on the prevalence of frailty
and to combine the data to synthesize the pooled prevalence of physical frailty
among patients with Alzheimer's disease. METHOD: Five electronic databases
(Embase, MEDLINE, CINAHL Plus, PsycINFO, and the Cochrane Library) were searched
for studies providing cross-sectional data on physical frailty among patients
with Alzheimer's disease published from 2000 to January 2016. RESULTS: Of 2,564
studies identified through the systematic review, five studies incorporating 534
patients with Alzheimer's disease were included for the meta-analysis. The
prevalence of frailty varied with a wide range from 11.1% to 50.0% and the pooled
prevalence was 31.9% (five studies, 95% confidence interval (CI)=15.7%-48.5%).
The high degree of heterogeneity was observed in all analyses. A borderline
publication bias was detected. CONCLUSION: The current study showed that frailty
is highly prevalent in older patients with Alzheimer's disease in the community
with the pooled prevalence of 31.9%. The true prevalence may be much higher given
that end-stage patients may not be included. This information is important for
clinicians and researchers.
PMID- 28413985
TI - Decrease in the Generation of Amyloid-beta Due to Salvianolic Acid B by
Modulating BACE1 Activity.
AB - OBJECTIVE: Generation and accumulation of the amyloid-beta (Abeta) peptide after
proteolytic processing of the full length amyloid precursor protein (FL-APP) by
beta-secretase (beta-site APP cleaving enzyme or BACE1) and gamma-secretase are
the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a
rate-limiting enzyme in the production of Abeta, is an attractive therapeutic
approach for the treatment of AD. Recent studies suggest that salvianolic acid B
(Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal
medicine commonly used for the treatment of cardiovascular, cerebrovascular and
liver diseases in China. METHOD: In this study, we discovered that Sal B acted as
a BACE1 modulator and reduced the level of secreted Abeta in two different
Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human
neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B
significantly and dose-dependently decreased the generation of extracellular
Abeta, soluble APPbeta (by-product of APP cleaved by BACE1), and intracellular C
terminal fragment beta from APP without influencing alpha-secretase and gamma
secretase activity and the levels of FL-APP. In addition, using protein-docking,
we determined the potential conformation of Sal B on BACE1 docking and revealed
the interactions of Sal B with the BACE1 catalytic center. RESULTS: The docking
provides a feasible explanation for the experimental results, especially in terms
of the molecular basis of Sal B's action. Our results indicate that Sal B is a
BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD.
PMID- 28413986
TI - Tau in Alzheimer's Disease: Mechanisms and Therapeutic Strategies.
AB - OBJECTIVE: Alzheimer's disease (AD), the most important progressive
neurodegenerative disorder, is characterized by cognitive and behavioral
disabilities. Nowadays, tau, as a microtubuleassociated protein and a principle
neuropathological hallmark of AD, provides us a neoteric perspective to explore
further aetiopathogenesis and therapeutic strategy. The hyperphosphorylation and
abnormal aggregation of tau, combined with its decreased clearance, form
neurofibrillary tangles (NFTs) and exert neurotoxicity in AD. METHODS: Recent
investigations aim to prevent the deposition of NFT and accelerate the clearance
of NFT. Intriguingly, immunization strategies targeting tau effectively
ameliorates the tau-associated pathology in AD. In addition, modified therapies
targeting tau should be regarded as a potential way to treat AD. These progresses
open new avenues for AD. CONCLUSION: Here, we review the recent literature of
potential mechanisms of the tau in AD and discuss the modified therapeutic
strategies for AD.
PMID- 28413987
TI - Alzheimer's Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration
of Neurodegeneration from Pro-inflammatory 'Wounding' to Anti-inflammatory
'Healing'.
AB - OBJECTIVE: The etiological initiators of neuroinflammation remain inconclusive,
and effective interventions to block neurodegeneration are unavailable.
Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that
usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)
like neurodegeneration in mice. CC not only upregulates the cerebral pro
inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and
interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10),
an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting
enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine. In
contrast, electroacupuncture (EA) elevates TNF-alpha/IL-8 and declines IL-10/TH
at first, but declines TNF-alpha/IL-8 and elevates IL-10/TH later. Upon impact on
mitochondrial biogenesis, ubiquitination, and autophagy, EA firstly potentates
but secondly attenuates CC-triggered signaling cascades leading to oxidation,
nitrosylation, hypoxia, and angiogenesis. Eventually, EA compromises
neurodegeneration by decreasing amyloid- beta peptide (Abeta) and phosphorylated
tau protein (p-tau), and also rectifies neuronal dysfunctions by increasing the
cholinergic neurotransmitter acetylcholine (Ach) and its rate-limiting
biosynthetic enzyme choline acetyltransferase (ChAT). RESULTS: Conclusively, EA
initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase
brain pathogenesis via conversion from pro-inflammatory microglia to anti
inflammatory microglia.
PMID- 28413988
TI - Cognitive Mechanisms in Decision-Making in Patients With Mild Alzheimer Disease.
AB - BACKGROUND: Alzheimer's dementia is characterized by significant cortical and
subcortical atrophy, causing diverse neuropsychological deficits. According to
the somatic marker hypothesis, the areas responsible for generating the somatic
markers that anticipate the consequences of a decision and thereby optimize the
process would be affected in these patients. OBJECTIVE: The aim of this
experiment is to study the decision-making processes in Alzheimer type dementia
patients to determine potential deficits in these processes as a result of the
disease, aside from the cognitive impairment that is typical of aging. In
addition, we wish to determine the defining characteristics of decision-making in
these patients, on the basis of the prospect valence-learning parameters. METHOD:
We evaluated 30 patients with Alzheimer's disease and a control group of 30
healthy subjects. A short version of the Iowa Gambling Task was used. RESULTS:
The results showed that patients made less advantageous choices than did
controls. Group differences were quantitative and qualitative, as significant
differences in cognitive mechanisms identified in the prospect valence-learning
decisions were observed. These results are consistent with evidence from
neuroimaging studies as well as with work carried out with amnesic patients.
CONCLUSION: That problems in our patients' decision-making could be due to the
characteristic memory deficits of this disease, which prevents them from
establishing new stimulus-reward relationships and eliminating previously learned
responses as a result of the parietal and temporal atrophy they present.
PMID- 28413989
TI - Anatomical Wrist Patterns on Plain Radiographs.
AB - BACKGROUND: Interpreting the structure in the wrist is complicated by the
existence of multiple joints as well as variability in bone shapes and anatomical
patterns. Previous studies have evaluated lunate and capitate shape in an attempt
to understand functional anatomical patterns. OBJECTIVE: The purpose of this
study was to describe anatomical shapes and wrist patterns in normal wrist
radiographs. We hypothesized that there is a significant relationship in the
midcarpal joint with at least one consistent pattern of wrist anatomy. METHOD:
Seventy plain posteroanterior (PA) and lateral wrist radiographs were evaluated.
These radiographs were part of a previously established normal database, had all
been read by a radiologist as normal, and had undergone further examination by 2
hand surgeons for quality. Evaluation included: lunate and capitate shape (type 1
and 2 lunate shape according to the classification system by Viegas et al.),
ulnar variance, radial inclination and height, and volar tilt. RESULTS: A
significant association was found between lunate and capitate shape using a
dichotomal classification system for both lunate and capitate shapes (p=0.003).
Type 1 wrists were defined as lunate type1and a spherical distal capitate. Type 2
wrists had a lunate type 2 and a flat distal capitate. No statistically
significant associations were detected between these wrist types and measurements
of the radiocarpal joint. CONCLUSION: There was a significant relationship
between the bone shapes within the midcarpal joint. These were not related to
radiocarpal anatomical shape. Further study is necessary to better describe the
two types of wrist patterns that were defined and to understand their influence
on wrist biomechanics and pathology.
PMID- 28413990
TI - Effect of Glucagon-like Peptide-1 Receptor Agonists on All-cause Mortality and
Cardiovascular Outcomes: A Meta-analysis.
AB - BACKGROUND: Cardiovascular disease is the leading cause of death in patients with
type 2 diabetes. OBJECTIVE: To assess the impact of glucagon-like peptide-1
receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant
outcomes including all-cause mortality, cardiovascular mortality, nonfatal
myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart
failure, in patients with type 2 diabetes. METHODS: EMBASE, MEDLINE, and CENTRAL
were searched (inception to September 2016) for randomized, double-blind, placebo
controlled trials of at least one year in duration that compared any GLP1RA to
placebo in patients with type 2 diabetes. Both authors independently completed
the literature search, data extraction, and risk of bias assessment. For each
outcome, a Risk Ratio (RR) and 95% Confidence Interval (CI) were calculated using
a Mantel-Haenszel random effects model. RESULTS: Eight trials (three albiglutide,
two lixisenatide, two liraglutide, one semaglutide) consisting of 21,135 patients
were included. Most patients had, or were at high risk for, cardiovascular
disease. Follow- up ranged from 1-3.8 years. Trials contributing the majority of
data were deemed to have a low risk of bias. The risk of all-cause mortality was
lowered by 11% in patients receiving a GLP1RA (RR 0.89, 95% CI 0.81-0.99). There
was no statistically significant difference between groups with respect to
cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalizations for heart
failure. CONCLUSION: GLP1RA therapy when compared to placebo reduced all-cause
mortality in high cardiovascular risk patients with type 2 diabetes. They did not
impact cardiovascular mortality, nonfatal MI, nonfatal stroke, or heart failure
hospitalizations.
PMID- 28413991
TI - Potential Role of Endothelin in Early Vascular Aging.
AB - Early vascular aging is a process associated with gradual alterations in the
vessels, regarding their structure and function, taking a more rapid course than
normal biological aging in the arteries. In the presence of cardiovascular
disease, these age-associated alterations are accelerated, contributing in the
appearance or the progression of cardiovascular disease, such as high blood
pressure, dyslipidemia, smoking and diabetes. Endothelin-1 (ET-1) is the most
abundant and important endothelin produced by vascular cells. ET-1 exerts its
biological actions through the activation of two receptors: ETA and ETB. Many
important functions are mediated by the activation of these receptors, such as
cardiovascular remodeling, vasoconstriction, cell proliferation and
differentiation, production of extracellular matrix, and water and sodium
secretion control. ETA receptor seems to participate in the pathogenesis and
development of diseases, such as diabetes, atherosclerosis, systemic and
pulmonary hypertension, and cardiac remodeling after myocardial ischemia, whereas
ETB receptor seems to prevent the overstimulation of ETA receptor, acting as a
clearance receptor. Increased ET-1 system activity may contribute to vascular
dysfunction in aging via multiple pathways, such as direct hemodynamic effects,
vascular oxidative stress, inflammatory activity, mitogenic stimulation of the
vascular smooth muscle cells and fibrotic processes. Endothelin receptor
antagonists were considered to be used for the treatment of some diseases like
hypertension, diabetes and chronic kidney disease. However, besides pulmonary
hypertension, this class is not in clinical use because of the side effects and
the availability of safer drugs for the treatment of these diseases.
PMID- 28413992
TI - Screening and Elucidation of Selected Natural Compounds for Anti- Alzheimer's
Potential Targeting BACE-1 Enzyme: A Case Computational Study.
AB - BACKGROUND: The present study clarifies the molecular interactions of human BACE1
with novel natural ligands and also with the well-known ligand 2, 2, 4
trihydroxychalcone and Galangin for comparison. OBJECTIVE: The study of enzyme-
ligands interaction is interesting, thus description of ligands binding to the
active site of target molecule could be beneficial for better understanding the
mechanism of the ligand on the target molecule. METHODS: Lipinski rule of five
and docking study were performed between ligands and enzyme using 'Autodock4.2'.
RESULTS: It was found that hydrogen bond interactions play a significant role in
the accurate positioning of ligands within the 'active site' of BACE1 to permit
docking. Such information may aid to propose the BACE1 -inhibitors and is
estimated to aid in the safe medical use of ligands. Selected ligands of BACE1
also inhibit the aggregated amyloid beta peptide. The aggregation of amyloid
peptides Abeta1-42 may be responsible for AD. CONCLUSION: Scope lies in the
determination of the 3-dimensional structure of BACE1 and ligands complex by X
ray crystallography to certify the explained data. To validate the enzyme
ligands results, we considered 2, 2, 4-trihydroxychalconeas and Galangin as a
positive control. Moreover, the current study verifies that ligands are more
capable inhibitors of human BACE1 compared to positive control with reference to
DeltaG values.
PMID- 28413993
TI - Efficacy of Sofosbuvir Plus Ribavirin with or Without Peginterferon- Alfa in
Treatment of a Cohort of Egyptian Patients with Hepatitis C Virus Infection.
AB - : Background & Aims: Sofosbuvir is a powerful drug for the treatment of hepatitis
C virus (HCV) infection. In comparison to preceding remedies, sofosbuvirbased
regimens provide a higher cure rate, fewer side effects, and much lower duration
of treatment. The aim of the work was to assess the efficacy and safety of
sofosbuvir plus ribavirin with or without peginterferon-alfa in the treatment of
a cohort of Egyptian patients with hepatitis C virus infection. METHODS: Two
hundred treatment naive patients who were HCV-antibody positive and HCV RNA by
PCR positive aged more than 18 years were enrolled in the study and patients were
classified into two groups: Group I which included 100 patients who received dual
therapy with sofosbuvir plus oral weight based ribavirin for 24 weeks and Group
II which included 100 patients on triple therapy with sofosbuvir plus oral weight
based ribavirin (as with the dual therapy) and a 180 mcg Peg-INF alpha 2a
subcutaneous injection weekly for 12 weeks. The primary end point was a sustained
virological response at 12 weeks after end of the treatment determined by
quantitative PCR for HCV. RESULTS: Both patients groups had high sustained
virological response that was higher in patients receiving triple than dual
therapy (94% vs 83%). The adverse events that occurred in the two groups of
patients were more evident in a group of patients receiving triple therapy. The
side effects were mainly flu like symptoms. CONCLUSIONS: The triple regimen of
Pegylated interferon, sofosbuvir plus ribavirin is safe and effective in the
treatment of Egyptian patients with hepatitis C virus as well as sofosbuvir and
ribavirin alone wit.
PMID- 28413994
TI - Biotic Strategies for Toxic Heavy Metal Decontamination.
AB - BACKGROUND: In the modern age of globalization and fast industrialization, the
environmental matters are fetching more and more annoyance for human being.
Patents reveal that heavy metals occur in immobilized form in sediments and as
aggregates in nature. However due to the different human activities like ore
mining and industrial processes, the natural biogeochemical cycles are disordered
instigating amplified deposition of heavy metals in aquatic environments. The
most common pollution causing heavy metals are considered to be the mercury,
arsenic, lead, copper, silver, cadmium. OBJECTIVE: The goal of this work is to
identify the biological action of heavy metal-contaminated water and sediments
which can be categorized into bioaccumulation, biosorption, oxidation/ reduction,
leaching, degradation, and phytoremediation. DISCUSSION: Among the various
biological methods for decontamination of heavy metals from water, biosorption is
known to be the most affordable, economical and efficient option for the
management of capacious water bodies encompassing low concentrations of heavy
metals. However, the physicochemical properties of the aquatic bodies that would
extremely affect the performances of biosorbents should be prudently measured.
The precipitation is efficient in decontamination/removal of relatively high
concentrations of metals in water. The bioleaching of searched sediments in
regulated systems is a speedy process as compared with phytoremediation.
CONCLUSION: In order to decontaminate the heavy metals from water, biological
methods are very proficient and useful. These methods can be very efficient in
cleaning up environment.
PMID- 28413995
TI - The burden of seasonal respiratory infections on a national telehealth service in
England.
AB - Seasonal respiratory illnesses present a major burden on primary care services.
We assessed the burden of respiratory illness on a national telehealth system in
England and investigated the potential for providing early warning of respiratory
infection. We compared weekly laboratory reports for respiratory pathogens with
telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple
linear regression was used to identify which pathogens had a significant
association with respiratory calls. Children aged <5 and 5-14 years, and adults
over 65 years were modelled separately as were time lags of up to 4 weeks between
calls and laboratory specimen dates. Associations with respiratory pathogens
explained over 83% of the variation in cold/flu, cough and difficulty breathing
calls. Based on the first two seasons available, the greatest burden was
associated with respiratory syncytial virus (RSV) and influenza, with
associations found in all age bands. The most sensitive signal for influenza was
calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting
models showed calls increasing a week before laboratory specimen dates. Daily
surveillance of these calls can provide early warning of seasonal rises in
influenza and RSV, contributing to the national respiratory surveillance
programme.
PMID- 28413996
TI - From VAP to VAE: Implications of the New CDC Definitions on a Burn Intensive Care
Unit Population.
AB - Ventilator-associated pneumonia (VAP) is a frequent complication of severe burn
injury. Comparing the current ventilator-associated event-possible VAP definition
to the pre-2013 VAP definition, we identified considerably fewer VAP cases in our
burn ICU. The new definition does not capture many VAP cases that would have been
reported using the pre-2013 definition. Infect Control Hosp Epidemiol 2017;38:867
869.
PMID- 28413998
TI - Optimising treatment strategies for ADHD in adolescence to minimise 'lost in
transition' to adulthood.
AB - The persistence of attention-deficit hyperactivity disorder (ADHD) from
adolescence to adulthood is not matched by continuity of care in this transition
period. Many adolescents with ADHD have poor medication adherence or even stop
medication treatment, and use of behavioural interventions is also suboptimal.
The present commentary focuses on treatment strategies that might improve effects
of ADHD medication treatment by improving adherence in adolescents with ADHD
and/or optimise behavioural interventions for ADHD in adolescence. Most treatment
strategies in adolescents with ADHD are merely copied from treatments offered to
children. Instead however treatment should be focused on what makes adolescents
special and vulnerable, such as poor insight into own functioning and poor
decision making. Techniques that offer promise for adolescents are motivational
interviewing, use of ecological momentary assessments and interventions,
mindfulness-based training and serious games. Systematic studies into the effects
of these techniques alone and in combination with medication are lacking.
PMID- 28413997
TI - Differences in meal patterns and timing with regard to central obesity in the
ANIBES ('Anthropometric data, macronutrients and micronutrients intake, practice
of physical activity, socioeconomic data and lifestyles in Spain') Study.
AB - OBJECTIVE: To study the association of meal patterns and timing with central
obesity to identify the best dietary strategies to deal with the increasing
obesity prevalence. DESIGN: A cross-sectional study performed on data from a
representative sample of the Spanish population. Height and waist circumference
were measured using standardized procedures and waist-to-height ratio (WHtR) was
calculated. The sample was divided into those without central obesity (WHtR<0.5)
and those with central obesity (WHtR>=0.5). SETTING: ANIBES ('Anthropometric
data, macronutrients and micronutrients intake, practice of physical activity,
socioeconomic data and lifestyles in Spain') Study. SUBJECTS: Adults aged 18-64
years (n 1655; 798 men and 857 women). RESULTS: A higher percentage of people ate
more than four meals daily in the group without central obesity and those with
central obesity more frequently skipped the mid-afternoon snack than those
without. Breakfasts containing >25 % of total energy intake and lunches
containing >35 % of total energy intake were associated with increased likelihood
of central obesity (OR=1.874, 95 % CI 1.019, 3.448; P15 % of total energy were
associated with decreased likelihood of central obesity (OR=0.477, 95 % CI 0.313,
0.727; P<0.001 and OR=0.650, 95 % CI 0.453, 0.932; P<0.05, respectively). The
variety of cereals, wholegrain cereals and dairy was higher in the population
without central obesity. CONCLUSIONS: Our results suggest that 'what and when we
eat' should be considered dietary strategies to reduce central obesity.
PMID- 28413999
TI - Improving Sensitivity to Detect Mild Cognitive Impairment: Cognitive Load Dual
Task Gait Speed Assessment.
AB - OBJECTIVES: Longitudinal research indicates that cognitive load dual-task gait
assessment is predictive of cognitive decline and thus might provide a sensitive
measure to screen for mild cognitive impairment (MCI). However, research among
older adults being clinically evaluated for cognitive concerns, a defining
feature of MCI, is lacking. The present study investigated the effect of
performing a cognitive task on normal walking speed in patients presenting to a
memory clinic with cognitive complaints. METHODS: Sixty-one patients with a mean
age of 68 years underwent comprehensive neuropsychological testing, clinical
interview, and gait speed (simple- and dual-task conditions) assessments. Thirty
four of the 61 patients met criteria for MCI. RESULTS: Repeated measure analyses
of covariance revealed that greater age and MCI both significantly associated
with slower gait speed, ps<.05. Follow-up analysis indicated that the MCI group
had significantly slower dual-task gait speed but did not differ in simple-gait
speed. Multivariate linear regression across groups found that executive
attention performance accounted for 27.4% of the variance in dual-task gait speed
beyond relevant demographic and health risk factors. CONCLUSIONS: The present
study increases the external validity of dual-task gait assessment of MCI.
Differences in dual-task gait speed appears to be largely attributable to
executive attention processes. These findings have clinical implications as they
demonstrate expected patterns of gait-brain behavior relationships in response to
a cognitive dual task within a clinically representative population. Cognitive
load dual-task gait assessment may provide a cost efficient and sensitive measure
to detect older adults at high risk of a dementia disorder. (JINS, 2017, 23, 493
501).
PMID- 28414000
TI - Maternal mind-mindedness and toddler behavior problems: The moderating role of
maternal trauma and posttraumatic stress.
AB - Maternal mind-mindedness (MM) reflects a caregiver's tendency to view a child as
an individual with an independent mind. Research has linked higher MM with more
favorable parenting and child adaptation. The aim of this study was to examine
whether MM was associated with toddlers' behavior problems and competence, and
the moderating role of trauma and posttraumatic stress disorder (PTSD) in a
sample (N = 212) of adolescent mothers and their toddlers. MM was coded from
maternal utterances during free play; mothers completed the University of
California at Los Angeles Trauma and Posttraumatic Stress Disorder Reaction Index
and reported on children's behavior problems and competence using the Brief
Infant-Toddler Social and Emotional Assessment. The majority of mothers (84%)
experienced trauma; 45% of these mothers met criteria for partial or full PTSD.
Trauma was related to greater behavior problems, and PTSD moderated MM-child
functioning relations. When mothers experienced full PTSD, there was no relation
between MM and behavior problems. With child competence, when compared to
children of mothers with no trauma exposure, children of mothers experiencing
partial PTSD symptoms were more likely to have delays in competence when mothers
made more MM comments. Results are discussed in light of how MM, in the context
of trauma and PTSD, may affect parenting.
PMID- 28414001
TI - Transcatheter closure of a residual aorto-left ventricular tunnel: report of a
case with a 6-year follow-up.
AB - Aorto-left ventricular tunnel is an exceedingly rare congenital cardiac defect.
Early surgical closure is the treatment of choice. Residual or recurrent tunnel
and aortic valve insufficiency are well-recognised complications after surgical
repair. In this article, we report on successful transcatheter closure of a
residual aorto-left ventricular tunnel using an Amplatzer duct occluder in a 7
year-old boy. The outcome after 6 years of follow-up is encouraging.
PMID- 28414003
TI - Regulatory theory: commercially sustainable markets rely upon satisfying the
public interest in obtaining credible goods.
AB - Regulatory theory is premised on the failure of markets, prompting a focus on
regulators and industry from economic perspectives. This article argues that
overlooking the public interest in the sustainability of commercial markets risks
markets failing completely. This point is exemplified through health care markets
- meeting an essential need - and focuses upon innovative medicines as the most
desired products in that market. If this seemingly invulnerable market risks
failure, there is a pressing need to consider the public interest in sustainable
markets within regulatory literature and practice. Innovative medicines are
credence goods, meaning that the sustainability of the market fundamentally
relies upon the public trusting regulators to vouch for product quality. Yet,
quality is being eroded by patent bodies focused on economic benefits from market
growth, rather than ensuring innovatory value. Remunerative bodies are not
funding medicines relative to market value, and market authorisation bodies are
not vouching for robust safety standards or confining market entry to products
for 'unmet medical need'. Arguably, this failure to assure quality heightens the
risk of the market failing where it cannot be substituted by the reputation or
credibility of providers of goods and/or information such as health care
professionals/institutions, patient groups or industry.
PMID- 28414002
TI - Global importation and population risk factors for measles in New Zealand: a case
study for highly immunized populations.
AB - As endemic measles is eliminated through immunization, countries must determine
the risk factors for the importation of measles into highly immunized populations
to target control measures. Despite eliminating endemic measles, New Zealand
suffers from outbreaks after introductions from abroad, enabling us to use it as
a model for measles introduction risk. We used a generalized linear model to
analyze risk factors for 1137 measles cases from 2007 to June 2014, provide
estimates of national immunity levels, and model measles importation risk. People
of European ethnicity made up the majority of measles cases. Age is a positive
risk factor, particularly 0-2-year-olds and 5-17-year-old Europeans, along with
increased wealth. Pacific islanders were also at greater risk, but due to 0-2
year-old cases. Despite recent high measles, mumps, and rubella vaccine
immunization coverage, overall population immunity against measles remains ~90%
and is lower in people born between 1982 and 2005. Greatest measles importation
risk is during December, and countries predicted to be sources have historical
connections and highest travel rates (Australia and UK), followed by Asian
countries with high travel rates and higher measles incidences. Our results
suggest measles importation due to travel is seeding measles outbreaks, and
immunization levels are insufficient to continue to prevent outbreaks because of
heterogeneous immunity in the population, leaving particular age groups at risk.
PMID- 28414004
TI - Clinical, virological and epidemiological characterization of dengue outbreak in
Myanmar, 2015.
AB - Hospital-based surveillance was conducted at two widely separated regions in
Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected
from 332 clinically diagnosed dengue patients during the peak season of dengue
cases. Viremia levels were measured by quantitative real-time PCR and plaque
assays using FcgammaRIIA-expressing and non-FcgammaRIIA-expressing BHK cells to
specifically determine the infectious virus particles. By serology and molecular
techniques, 280/332 (84.3%) were confirmed as dengue patients. All four serotypes
of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients
including two cases infected with two DENV serotypes. High percentage of primary
infection was noted among the severe dengue patients. Patients with primary
infection or DENV IgM negative demonstrated significantly higher viral loads but
there was no significant difference among the severity groups. Viremia levels
among dengue patients were notably high for a long period which was assumed to
support the spread of the virus by the mosquito vector during epidemic.
Phylogenetic analyses of the envelope gene of the epidemic strains revealed close
similarity with the strains previously isolated in Myanmar and neighboring
countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3)
and genotype distributions were similar in both study sites.
PMID- 28414005
TI - Health care and health innovation in Europe: regulating for public benefit or for
commercial profit?
PMID- 28414006
TI - Unit cost of common illness management: a comparison between a primary care unit
and a community pharmacy in Thailand.
AB - : Aim This study was to perform unit cost analysis of managing common illnesses
comparing between a primary care unit (PCU) and a community pharmacy. BACKGROUND:
PCU is a key point of access for primary care in Thailand. Although a community
pharmacy is an ideal setting, it has not been successfully incorporated in
Thailand's health service. Common illnesses are encountered everyday by community
pharmacists, an appropriate compensation for this service has not been
established. METHODS: A primary care service of one educational institution was a
study site. Eight common illnesses were emphasised. Patient visits were observed,
prospectively at community pharmacy and retrospectively at PCU, during August to
October 2013. Labour and material costs related to management of common illnesses
were recorded. Total cost divided by total patient visits determined the unit
cost. For the community pharmacy, patients were followed up after 3-14 days of
visit to evaluate the effectiveness. Sensitivity analysis was performed by
varying direct medical cost at +/-10-30%. Findings At the community pharmacy,
community pharmacists performed multiple tasks including interviewing and
assessing patients, choosing an appropriate treatment and dispensing. Of 9141
visits, 775 (8.5%) with common illnesses were included. Upper respiratory
disorder was found the highest 41.9% (325/755). Unit cost of treatment ranged
from 54.16 baht (L1.18) for pain to 82.71 baht (L1.80) for skin disorder. Two
thirds of pharmacy visits (77.9%, 539/692) reported complete recovery. Managing
common illnesses at the PCU was performed by nurse assistants, nurses, doctors
and pharmacists. Of 6701 patient visits to the PCU, 1545 (23.1%) visits were at
least one of the eight illnesses. Upper respiratory disorder was the majority,
53.0% (771/1454). Unit cost of treatment ranged from 85.39 baht (L1.86) for
eye/ear to 245.93 baht (L5.36) for sexual health. Managing common illness at a
community pharmacy shows satisfactory effectiveness with lower unit cost.
PMID- 28414007
TI - Pokemon Go: digital health interventions to reduce cardiovascular risk.
AB - Physical activity is associated with a lower risk of coronary heart
disease/cardiovascular disease mortality, and current guidelines recommend
physical activity for primary prevention in healthy individuals and secondary
prevention in patients with coronary heart disease/cardiovascular disease. Over
the last decade, playing classic video games has become one of the most popular
leisure activities in the world, but is associated with a sedentary lifestyle. In
the new era of rapidly evolving augmented reality technology, Pokemon Go, a well
known augmented reality game, may promote physical activity and prevent
cardiovascular disease risks - that is, diabetes, obesity, and hypertension.
Pokemon Go makes players willing to be physically active for regular and long
periods of time. We report on an assessment of regular walking and playing
Pokemon Go by performing data mining in Twitter.
PMID- 28414008
TI - Implementation, utilization and influence of a community-based participatory
nutrition promotion programme in rural Ethiopia: programme impact pathway
analysis.
AB - OBJECTIVE: A community-based participatory nutrition promotion (CPNP) programme,
involving a 2-week group nutrition session, attempted to improve child feeding
and hygiene. The implementation, utilization and influence of the CPNP programme
were examined by programme impact pathway (PIP) analysis. DESIGN: Five CPNP
programme components were evaluated: (i) degree of implementation; (ii)
participants' perception of the nutrition sessions; (iii) participants' message
recall; (iv) utilization of feeding and hygiene practices at early programme
stage; and (v) participants' engagement in other programmes. SETTING: Habro and
Melka Bello districts, Ethiopia. SUBJECTS: Records of 372 nutrition sessions, as
part of a cluster-randomized trial, among mothers (n 876 in intervention area, n
914 in control area) from a household survey and CPNP participants (n 197) from a
recall survey. RESULTS: Overall, most activities related to nutrition sessions
were successfully operated with high fidelity (>90 %), but a few elements of the
protocol were only moderately achieved. The recall survey among participants
showed a positive perception of the sessions (~90 %) and a moderate level of
message recall (~65 %). The household survey found that the CPNP participants had
higher minimum dietary diversity at the early stage (34.0 v. 19.9 %, P=0.01) and
a higher involvement in the Essential Nutrition Action (ENA) programme over a
year of follow-up (28.2 v. 18.3 %; P<0.0001) compared with non-participants
within the intervention area. CONCLUSIONS: Our PIP analysis suggests that CPNP
was feasibly implemented, promoted a sustained utilization of proper feeding
behaviours, and enhanced participation in the existing ENA programme. These
findings provide a possible explanation to understanding CPNP's effectiveness.
PMID- 28414009
TI - Adenosine Triphosphate Quantification Correlates Poorly with Microbial
Contamination of Duodenoscopes.
AB - OBJECTIVE The aim of this study was to quantify the correlation between adenosine
triphosphate (ATP) measurements and bacterial cultures from duodenoscopes for
evaluation of contamination following high-level disinfection. DESIGN
Duodenoscopes used for any intended endoscopic retrograde
cholangiopancreatography (ERCP) procedure were included. Microbiologic and ATP
data were collected concomitantly and in the same manner from ERCP duodenoscopes.
SETTING A high-volume endoscopy unit at a tertiary referral acute-care facility.
METHODS Duodenoscopes were sampled for ATP and bacterial contamination in a
contemporaneous and highly standardized fashion using a "flush-brush-flush"
method for the working channel (WC) and a dry flocked swab for the elevator
mechanism (EM). Specimens were processed for any aerobic bacterial growth (colony
forming units, CFU). Growth of CFU>0 and ATP relative light unit (RLU)>0 was
considered a contaminated result. Frequency of discord between among WC and EM
measurements were calculated using 2*2 contingency tables. The Spearman
correlation coefficient was used to calculate the relatedness of bacterial
contamination and ATP as continuous measurements. RESULTS The Spearman
correlation coefficient did not demonstrate significant relatedness between ATP
and CFU for either a WC or EM site. Among 390 duodenoscope sampling events, ATP
and CFU assessments of contamination were discordant in 82 of 390 WC measurements
(21%) and 331 of 390 of EM measurements (84.9%). The EM was frequently and
markedly positive by ATP measurement. CONCLUSION ATP measurements correlate
poorly with a microbiologic standard assessing duodenoscope contamination,
particularly for EM sampling. ATP may reflect biological material other than
nonviable aerobic bacteria and may not serve as an adequate marker of bacterial
contamination. Infect Control Hosp Epidemiol 2017;38:678-684.
PMID- 28414010
TI - Letter to the Editor: Beyond childhood trauma - stressful events early and later
in life in relation to psychotic experiences.
PMID- 28414011
TI - Transradial approach for collateral embolisation.
AB - Significant aortopulmonary collaterals in cyanotic CHD patients require closure
immediately before definitive intracardiac repair. Traditionally, the
transfemoral access has been used for this purpose; however in a few cases,
selective and stable hooking of collaterals may be extremely difficult. We
describe a case in which we used a new approach for collateral embolisation in a
difficult situation.
PMID- 28414012
TI - Reasons for optimism in the search for new vaccines for tuberculosis.
AB - In the development of vaccines for tuberculosis (TB), the combination of the
will, funding, scientific rigor, new tools, refined animal models and improved
clinical trial designs are all converging at an opportune moment. The lack of
optimism that has surrounded the likelihood for finding novel TB vaccines has
resulted from a lack of correlates of vaccine-induced protection, a lack of tool
candidate vaccines to probe the immunologic space, which may be needed, and the
negative result of one recent trial. A vaccine for TB that can be delivered at a
reasonable cost to the marketplace will have greater impact on the incidence of
new cases of TB than any intervention in world history. Now is the time to
increase resources, both financial and human intellectual capacity, for a global
tuberculosis vaccine effort.
PMID- 28414013
TI - The efficacy of primary care chaplaincy compared with antidepressants: a
retrospective study comparing chaplaincy with antidepressants.
AB - : Aim To determine the effectiveness of primary care chaplaincy (PCC) when used
as the sole intervention, with outcomes being compared directly with those of
antidepressants. This was to be carried out in a homogenous study population
reflective of certain demographics in the United Kingdom. BACKGROUND: Increasing
numbers of patients are living with long-term conditions and 'modern maladies'
and are experiencing loss of well-being and depression. There is an increasing
move to utilise non-pharmacological interventions such as 'talking therapies'
within this context. Chaplaincy is one such 'talking therapy' but within primary
care its evidence base is sparse with only one quantitative study to date. There
is therefore a need to evaluate PCC excluding those co-prescribed
antidepressants, as this is not evidenced in the literature as yet. PCC also
needs to be directly compared with the use of antidepressants to justify its use
as a valid alternative treatment for loss of well-being and depression. METHODS:
This was a retrospective observational study based on routinely collected data.
There were 107 patients in the PCC group and 106 in the antidepressant group.
Socio-demographic data were collected. Their pre- and post-intervention (either
chaplaincy or antidepressant) well-being was assessed, by the Warwick-Edinburgh
Mental Well-being Scale (WEMWBS) which is a validated Likert scale. Findings The
majority of both groups were female with both groups showing marked ethnic
homogeneity. PCC was associated with a significant and clinically meaningful
improvement in well-being at a mean follow-up of 80 days. This treatment effect
was maintained after those co-prescribed antidepressants were removed. PCC was
associated with an improvement in well-being similar to that of antidepressants
with no significant difference between the two groups.
PMID- 28414014
TI - Do DSM-5 Section II personality disorders and Section III personality trait
domains reflect the same genetic and environmental risk factors?
AB - BACKGROUND: DSM-5 includes two conceptualizations of personality disorders (PDs).
The classification in Section II is identical to the one found in DSM-IV, and
includes 10 categorical PDs. The Alternative Model (Section III) includes
criteria for dimensional measures of maladaptive personality traits organized
into five domains. The degree to which the two conceptualizations reflect the
same etiological factors is not known. METHODS: We use data from a large
population-based sample of adult twins from the Norwegian Institute of Public
Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory
that indexes the five domains of the DSM-5 Alternative Model plus a domain
explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline,
Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the
maladaptive personality traits and 10 years previously. Schizoid, Histrionic,
Narcissistic, and Dependent PDs were only assessed at the first interview.
Biometric models were used to estimate overlap in genetic and environmental risk
factors. RESULTS: When measured concurrently, there was 100% genetic overlap
between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial,
Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared
with the domains. Genetic correlations between the individual domains and PDs
ranged from +0.21 to +0.91. CONCLUSION: The pathological personality trait
domains, which are part of the Alternative Model for classification of PDs in DSM
5 Section III, appears to tap, at an aggregate level, the same genetic risk
factors as the DSM-5 Section II classification for most of the PDs.
PMID- 28414015
TI - Effects of depression, metabolic syndrome, and cardiorespiratory fitness on
mortality: results from the Cooper Center Longitudinal Study.
AB - BACKGROUND: Depression and metabolic syndrome (MetS) are frequently comorbid
disorders that are independently associated with premature mortality. Conversely,
cardiorespiratory fitness (CRF) is associated with reduced mortality risk. These
factors may interact to impact mortality; however, their effects have not been
assessed concurrently. This analysis assessed the mortality risk of comorbid
depression/MetS and the effect of CRF on mortality in those with depression/MetS.
METHODS: Prospective study of 47 702 adults in the Cooper Center Longitudinal
Study. Mortality status was attained from the National Death Index. History of
depression was determined by patient response (yes or no) to a standardized
medical history questionnaire. MetS was categorized using the American Heart
Association/National Heart, Lung, and Blood Institute criteria. CRF was estimated
from the final speed/grade of a treadmill graded exercise test. RESULTS: 13.9%
reported a history of depression, 21.4% met criteria for MetS, and 3.0% met
criteria for both MetS and history of depression. History of depression (HR =
1.24, p = 0.003) and MetS (HR = 1.28, p < 0.001) were independently associated
with an increased mortality risk, with the greatest mortality risk among
individuals with both a history of depression and MetS (HR = 1.59, p < 0.001).
Higher CRF was associated with a significantly lower risk of mortality (p <
0.001) in all individuals, including those with MetS and/or a history of
depression. CONCLUSIONS: Those with higher levels CRF had reduced mortality risk
in the context of depression/MetS. Interventions that improve CRF could have
substantial impact on the health of persons with depression/MetS.
PMID- 28414016
TI - Accidental Occupational Exposure to Burkholderia pseudomallei in South Korea Did
Not Result in Melioidosis.
PMID- 28414017
TI - The prevalence of antenatal and postnatal co-morbid anxiety and depression: a
meta-analysis.
AB - To date, the precise prevalence of co-morbidity of anxiety and depression in the
perinatal period is not well known. We aimed to estimate the prevalence of co
morbid anxiety and depression in the antenatal and postnatal periods. Systematic
searches of multiple electronic databases were conducted for studies published
between January 1950 and January 2016. We included 66 (24 published and 42
unpublished) studies incorporating 162 120 women from 30 countries. Prevalence of
self-reported antenatal anxiety symptoms and mild to severe depressive symptoms
was 9.5% [95% confidence interval (CI) 7.8-11.2, 17 studies, n = 25 592] and of
co-morbid anxiety symptoms and moderate/severe depressive symptoms was 6.3% (95%
CI 4.8-7.7, 17 studies, n = 27 270). Prevalence of a clinical diagnosis of any
antenatal anxiety disorder and depression was 9.3% (95% CI 4.0-14.7, 10 studies,
n = 3918) and of co-morbid generalized anxiety disorder and depression was 1.7%
(95% CI 0.2-3.1, three studies, n = 3085). Postnatally between 1 and 24 weeks
postpartum, the prevalence of co-morbid anxiety symptoms and mild to severe
depressive symptoms was 8.2% (95% CI 6.5-9.9, 15 studies, n = 14 731), while co
morbid anxiety symptoms and moderate/severe depressive symptoms was 5.7% (95% CI
4.3-7.1, 13 studies, n = 20 849). The prevalence of a clinical diagnosis of co
morbid anxiety and depression was 4.2% (95% CI 1.9-6.6, eight studies, n = 3251).
Prevalence rates did not differ with regard to year of publication, country
income, selection bias and attrition bias. The results suggest that co-morbid
perinatal anxiety and depression are prevalent and warrant clinical attention
given the potential negative child developmental consequences if left untreated.
Further research is warranted to develop evidence-based interventions for
prevention, identification and treatment of this co-morbidity.
PMID- 28414018
TI - Psychological flexibility mediates change in intuitive eating regulation in
acceptance and commitment therapy interventions.
AB - OBJECTIVE: Despite the promising results related to intuitive eating, few studies
have attempted to explain the processes encouraging this adaptive eating
behaviour. The focus of the present study was on exploring mechanisms of change
in intuitive eating and weight in acceptance and commitment therapy (ACT)
interventions. Mediation provides important information regarding the treatment
processes and theoretical models related to specific treatment approaches. The
study investigates whether psychological flexibility, mindfulness skills and
sense of coherence mediated the interventions' effect on intuitive eating and
weight. DESIGN: Secondary analysis of a randomized control trial. Mediation
analysis compared two ACT interventions - face-to-face (in a group) and mobile
(individually) - with a control group using a latent difference score model.
Settings Data were collected in three Finnish towns. SUBJECTS: The participants
were overweight or obese (n 219), reporting symptoms of perceived stress.
RESULTS: The effect of the interventions on participants' (i) BMI, (ii) intuitive
eating and its subscales, (iii) eating for physical rather than emotional reasons
and (iv) reliance on internal hunger and satiety cues was mediated by changes in
weight-related psychological flexibility in both ACT groups. CONCLUSIONS: These
findings suggest that ACT interventions aiming for lifestyle changes mediate the
intervention effects through the enhanced ability to continue with valued
activities even when confronted with negative emotions and thoughts related to
weight.
PMID- 28414019
TI - Parental depressive history, parenting styles, and child psychopathology over 6
years: The contribution of each parent's depressive history to the other's
parenting styles.
AB - The link between parental depressive history and parenting styles is well
established, as is the association of parenting with child psychopathology.
However, little research has examined whether a depressive history in one parent
predicts the parenting style of the other parent. As well, relatively little
research has tested transactional models of the parenting-child psychopathology
relationship in the context of parents' depressive histories. In this study,
mothers and fathers of 392 children were assessed for a lifetime history of major
depression when their children were 3 years old. They then completed measures of
permissiveness and authoritarianism and their child's internalizing and
externalizing symptoms when children were 3, 6, and 9 years old. The results
showed that a depressive history in one parent predicted the other parent's
permissiveness. Analyses then showed that child externalizing symptoms at age 3
predicted maternal permissiveness and authoritarianism and paternal
permissiveness at age 6. Maternal permissiveness at age 6 predicted child
externalizing symptoms at age 9. No relationships in either direction were found
between parenting styles and child internalizing symptoms. The results highlight
the importance of considering both parents' depressive histories when
understanding parenting styles, and support transactional models of parenting
styles and child externalizing symptoms.
PMID- 28414020
TI - Modifying Alcohol Consumption to Reduce Obesity (MACRO): development and
feasibility trial of a complex community-based intervention for men.
AB - BACKGROUND: Obese men who consume alcohol are at a greatly increased risk of
liver disease; those who drink > 14 units of alcohol per week have a 19-fold
increased risk of dying from liver disease. OBJECTIVES: To develop an
intervention to reduce alcohol consumption in obese men and to assess the
feasibility of a randomised controlled trial (RCT) to investigate its
effectiveness. DESIGN OF THE INTERVENTION: The intervention was developed using
formative research, public involvement and behaviour change theory. It was
organised in two phases, comprising a face-to-face session with trained laypeople
(study co-ordinators) followed by a series of text messages. Participants
explored how alcohol consumption contributed to weight gain, both through direct
calorie consumption and through its effect on increasing food consumption,
particularly of high-calorie foodstuffs. Men were encouraged to set goals to
reduce their alcohol consumption and to make specific plans to do so. The
comparator group received an active control in the form of a conventional alcohol
brief intervention. Randomisation was carried out using the secure remote web
based system provided by the Tayside Clinical Trials Unit. Randomisation was
stratified by the recruitment method and restricted using block sizes of randomly
varying lengths. Members of the public were involved in the development of all
study methods. SETTING: Men were recruited from the community, from primary care
registers and by time-space sampling (TSS). The intervention was delivered in
community settings such as the participant's home, community centres and
libraries. PARTICIPANTS: Men aged 35-64 years who had a body mass index (BMI) of
> 30 kg/m2 and who drank > 21 units of alcohol per week. RESULTS: The screening
methods successfully identified participants meeting the entry criteria. Trial
recruitment was successful, with 69 men (36 from 419 approached in primary care,
and 33 from 470 approached via TSS) recruited and randomised in 3 months. Of the
69 men randomised, 35 were allocated to the intervention group and 34 to the
control group. The analysis was conducted on 31 participants from the
intervention group and 30 from the control group. The participants covered a wide
range of ages and socioeconomic statuses. The average alcohol consumption of the
men recruited was 47.2 units per week, more than twice that of the entry
criterion (> 21 units per week). Most (78%) engaged in binge drinking (> 8 units
in a session) at least weekly. Almost all (95%) exceeded the threshold for a 19
fold increase in the risk of dying from liver disease (BMI of > 30 kg/m2 and > 14
units of alcohol per week). Despite this, they believed that they were at low
risk of harm from alcohol, possibly because they seldom suffered acute harms
(e.g. hangovers) and made few visits to a general practitioner or hospital.
INTERVENTION: The intervention was delivered with high fidelity. A high follow-up
rate was achieved (98%) and the outcomes for the full RCT were measured. A
process evaluation showed that participants engaged with the main components of
the intervention. The acceptability of the study methods was high. CONCLUSIONS:
This feasibility study developed a novel intervention and evaluated all of the
stages of a RCT that would test the effectiveness of the intervention. The main
stages of a trial were completed successfully: recruitment, randomisation,
intervention delivery, follow-up and measurement of study outcomes. Most of the
men recruited drank very heavily and were also obese. This places them at a very
high risk of liver disease, making them a priority for intervention. FUTURE WORK:
A RCT to test the effectiveness and cost-effectiveness of the intervention. TRIAL
REGISTRATION: Current Controlled Trials ISRCTN55309164. FUNDING: This project was
funded by the National Institute for Health Research (NIHR) Health Technology
Assessment programme and will be published in full in Health Technology
Assessment; Vol. 21, No. 19. See the NIHR Journals Library website for further
project information.
PMID- 28414021
TI - Elliptical broken line method for calculating capillary density in nailfold
capillaroscopy: Proposal and evaluation.
AB - Nailfold capillaroscopy is a practical method for identifying and obtaining
morphological changes in capillaries which might reveal relevant information
about diseases and health. Capillaroscopy is harmless, and seems simple and
repeatable. However, there is lack of established guidelines and instructions for
acquisition as well as the interpretation of the obtained images; which might
lead to various ambiguities. In addition, assessment and interpretation of the
acquired images are very subjective. In an attempt to overcome some of these
problems, in this study a new modified technique for assessment of nailfold
capillary density is introduced. The new method is named elliptic broken line
(EBL) which is an extension of the two previously known methods by defining clear
criteria for finding the apex of capillaries in different scenarios by using a
fitted elliptic. A graphical user interface (GUI) is developed for pre
processing, manual assessment of capillary apexes and automatic correction of
selected apexes based on 90 degrees rule. Intra- and inter-observer reliability
of EBL and corrected EBL is evaluated in this study. Four independent observers
familiar with capillaroscopy performed the assessment for 200 nailfold
videocapillaroscopy images, form healthy subject and systemic lupus erythematosus
patients, in two different sessions. The results show elevation from moderate
(ICC=0.691) and good (ICC=0.753) agreements to good (ICC=0.750) and good
(ICC=0.801) for intra- and inter-observer reliability after automatic correction
of EBL. This clearly shows the potential of this method to improve the
reliability and repeatability of assessment which motivates us for further
development of automatic tool for EBL method.
PMID- 28414022
TI - Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell
Carcinoma.
AB - Sunlight is the principal environmental risk factor for keratinocyte cancers, but
other carcinogens have also been implicated, including tobacco smoke. Findings
have been conflicting, however. We investigated associations between cigarette
smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma
(SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history
was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained
through data linkage and verified by histopathology reports. We restricted
analyses to white participants who at baseline reported no past history of skin
cancer excisions and no more than five destructively treated actinic skin
lesions. We fitted Cox proportional hazards models, adjusted for known
confounders. Compared with never smokers, current smokers had significantly lower
risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but
significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval =
1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers.
Among smokers, we observed no dose-response trends with duration of smoking,
intensity, or time since quitting. On further analysis, current smokers had fewer
skin examinations and procedures than never smokers, suggesting greater
opportunities for detection among never smokers. Strengths include large sample
size, prospective design, and virtually complete follow-up; however, histologic
details were missing for a proportion of excised tumors. In conclusion, current
smokers had a lower incidence of BCC (possibly because of detection bias) but
higher rates of SCC.
PMID- 28414023
TI - Effect of spatial and temporal stimulus parameters on the maturation of global
motion perception.
AB - There are discrepancies with respect to the age at which adult-like performance
is reached on tasks assessing global motion perception. This is in part because
performance in children depends on stimulus parameters. We recently showed that
five-year-olds demonstrated adult-like performance over a range of speeds when
the speed ratio was comprised of longer spatial and temporal displacements; but
displayed immature performance when the speed ratio was comprised of shorter
displacements. The goal of the current study was to assess the effect of these
global motion stimulus parameters across a broader age range in order to estimate
the age at which mature performance is reached. Motion coherence thresholds were
assessed in 182 children and adults aged 7-30years. Dot displacement (Deltax) was
1, 5, or 30min of arc; frame duration (Deltat) was 17 or 50ms. This created a
total of six conditions. Consistent with our previous results, coherence
thresholds in the youngest children assessed were adult-like at the two
conditions with the largest Deltax. Maturity was reached around age 12 for the
medium Deltax, and by age 16 for the smallest Deltax. Performance did not appear
to be affected by Deltat. This late maturation may reflect a long developmental
period for cortical networks underlying global motion perception. These findings
resolve many of the discrepancies across previous studies, and should be
considered when using global motion tasks to assess children with atypical
development.
PMID- 28414025
TI - Alterations of the translation apparatus during aging and stress response.
AB - Aging is a biological process characterized by the irreversible and time
dependent deterioration of cell functions, tissues, and organs. Accumulating
studies in a wide range of species from yeast to human revealed changes
associated with the aging process to be conserved throughout evolution. The main
characteristics of aging are (i) genomic instability, (ii) loss of telomere
function, (iii) epigenetic changes,(iv) increased cellular senescence, (v)
depletion of the stem cell pool, (vi) altered intercellular communication and
(vii) loss of protein homeostasis. Among the multiple molecular mechanisms
underlying aging, alterations of the translation machinery affecting the rate and
selectivity of protein biosynthesis seem to play a central role. At the very
heart of translation is the ribosome, a multifaceted and universally conserved
RNA-protein particle responsible for accurate polypeptide synthesis and co
translational protein folding. Here we summarize and discuss recent developments
on the contribution of altered translation and age-dependent modifications on the
ribosome structure to aging and cellular senescence.
PMID- 28414024
TI - Novel high-throughput cell-based hybridoma screening methodology using the Celigo
Image Cytometer.
AB - Hybridoma screening is a critical step for antibody discovery, which necessitates
prompt identification of potential clones from hundreds to thousands of hybridoma
cultures against the desired immunogen. Technical issues associated with ELISA-
and flow cytometry-based screening limit accuracy and diminish high-throughput
capability, increasing time and cost. Conventional ELISA screening with coated
antigen is also impractical for difficult-to-express hydrophobic membrane
antigens or multi-chain protein complexes. Here, we demonstrate novel high
throughput screening methodology employing the Celigo Image Cytometer, which
avoids nonspecific signals by contrasting antibody binding signals directly on
living cells, with and without recombinant antigen expression. The image
cytometry-based high-throughput screening method was optimized by detecting the
binding of hybridoma supernatants to the recombinant antigen CD39 expressed on
Chinese hamster ovary (CHO) cells. Next, the sensitivity of the image cytometer
was demonstrated by serial dilution of purified CD39 antibody. Celigo was used to
measure antibody affinities of commercial and in-house antibodies to membrane
bound CD39. This cell-based screening procedure can be completely accomplished
within one day, significantly improving throughput and efficiency of hybridoma
screening. Furthermore, measuring direct antibody binding to living cells
eliminated both false positive and false negative hits. The image cytometry
method was highly sensitive and versatile, and could detect positive antibody in
supernatants at concentrations as low as ~5ng/mL, with concurrent Kd binding
affinity coefficient determination. We propose that this screening method will
greatly facilitate antibody discovery and screening technologies.
PMID- 28414026
TI - Targeting Oct2 and P53: Formononetin prevents cisplatin-induced acute kidney
injury.
AB - Nephrotoxicity is one of major side effects of cisplatin in chemotherapy.
Therefore, there is an urgent medical need to develop drugs that may protect
kidney from toxicity. In previous study, we found that it showed the protective
effects of formononetin against apoptosis by upregulating Nrf2. In this study, we
investigated the renoprotective effect of formononetin against cisplatin-induced
AKI and tried to elucidate the possible mechanisms. The amelioration of renal
function, histopathological changes, and apoptosis in tubular cells was observed
after formononetin treatment. Formononetin decreased expression of organic cation
transporter 2 (Oct2) and increased the expressions of multidrug resistance
associated proteins (Mrps), which might result in a decrease accumulation of
cisplatin in tubular cells after AKI. 5-Bromo-2-deoxyuridine (BrdU) and Ki-67
staining assay indicated that formononetin could promote the renal tubular cells
proliferation after cisplatin nephrotoxicity. Moreover, formononetin regulated
cyclins and pro-apoptotic proteins to involve the regulation of cell cycle.
Furthermore, formononetin decreased p53 expression via promoting the
overexpression of murine double minute 2 (MDM2) and MDMX. Taken together,
formononetin provided protective effects by promoting proliferation of surviving
renal tubular cells and inhibiting apoptosis after cisplatin-induced AKI.
PMID- 28414027
TI - Arsenic activates the expression of 3beta-HSD in mouse Leydig cells through
repression of histone H3K9 methylation.
AB - Arsenic exposure has been associated with male reproductive dysfunction by
disrupting steroidogenesis; however, the roles of epigenetic drivers, especially
histone methylation in arsenic-induced steroidogenic toxicity remain not well
documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9)
methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to
arsenic exposure. Our results indicated that mRNA and protein expression levels
of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were both significantly up
regulated while the rest of key genes involved in steroidogenesis were down
regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di
and tri-methylation (H3K9me2/3) levels in MLTC-1 cells. Since H3K9 demethylation
leads to gene activation, we further investigated whether the induction of 3beta
HSD expression was ascribed to reduced H3K9 methylation. The results showed that
H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly
attenuated the decrease of H3K9me2/3 and increase of 3beta-HSD expression induced
by arsenic. To further elucidate the mechanism for the activation of 3beta-HSD,
we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which
also showed significant decrease of H3K9me2/3 in the investigated region after
arsenic exposure. Considering these results, we conclude that arsenic exposure
induced 3beta-HSD up-regulation by suppressing H3K9me2/3 status, which is
suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1
cells.
PMID- 28414028
TI - Culex (Culiciomyia) sasai (Diptera: Culicidae), senior synonym of Cx.
spiculothorax and a new country record for Bhutan.
AB - Culex (Culiciomyia) spiculothorax was described from Thailand based on the
presence of spiculation on the thorax of larvae. Adult females are characterized
but are indistinguishable from those of related species, such as Cx.
pallidothorax. Phylogenetic analysis of mitochondrial oxidase subunit I (COI)
sequences revealed that specimens identified as Cx. spiculothorax from Thailand,
Japan and Bhutan form a single clade with Cx. sasai from Japan (Kimura 2
parameter genetic distances 0-0.9%) that is clearly distinct from clades
comprised of other species of subgenus Culiciomyia. Attempts to collect Cx. sasai
from several locations in Japan were unsuccessful - only larvae with thoracic
vesicular-like spicules identified as Cx. spiculothorax were collected. Careful
examination of specimens collected near the type locality of Cx. sasai revealed
the presence of spicules on the thorax. Based on these findings, Cx.
spiculothorax is formally synonymized with Cx. sasai, which replaces the former
as the species present in Thailand and is a new country record for Bhutan.
PMID- 28414030
TI - POINT: Are Advanced Practice Professionals More Likely to Achieve Better Tobacco
Cessation Results than Physicians? Yes.
PMID- 28414031
TI - Rebuttal From Dr Hitsman et al.
PMID- 28414029
TI - How Well Does CAPTURE Translate?: An Exploratory Analysis of a COPD Case-Finding
Method for Spanish-Speaking Patients.
AB - BACKGROUND: This study tested the properties of a Spanish translation of CAPTURE
(COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and
Exacerbation Risk) with selective use of peak expiratory flow (PEF). METHODS:
This study comprised analyses of data from the Spanish-speaking cohort of the
cross-sectional, case-control study used to develop CAPTURE. Translation
procedures included forward and backward translation, reconciliation, and
cognitive interviewing to assure linguistic and cultural equivalence, yielding
CAPTURE-S. Spanish-speaking participants were recruited through one center and
designated as case subjects (clinically significant COPD: FEV1 <= 60% predicted
and/or at risk of COPD exacerbation) or control subjects (no or mild COPD).
Subjects completed a questionnaire booklet that included 44 candidate items, the
COPD Assessment Test (CAT), and the modified Medical Research Council (mMRC)
dyspnea question. PEF and spirometry were also performed. RESULTS: The study
included 30 participants (17 case subjects and 13 control subjects). Their mean
(+/- SD) age was 62.6 (11.49) years, and 33% were male. CAPTURE-S scores were
significantly correlated with PEF (r = -0.78), the FEV1/FVC ratio (r = -0.74),
FEV1 (r = -0.69), FEV1 % predicted (r = -0.69), the CAT score (r = 0.70), and the
mMRC dyspnea question (r = 0.59) (P < .0001), with significantly higher scores in
case subjects than in control subjects (t = 6.16; P < .0001). PEF significantly
correlated with FEV1 (r = 0.89), FEV1 % predicted (r = 0.79), and the FEV1/FVC
ratio (r = 0.75) (P < .0001), with significantly lower PEF in case subjects than
in control subjects (t = 5.08; P < .0001). CAPTURE-S score + PEF differentiated
case subjects and control subjects with a sensitivity of 88.2% and a specificity
of 92.3%. CONCLUSIONS: CAPTURE-S with selective use of PEF seems to be useful for
identifying Spanish-speaking patients in need of diagnostic evaluation for
clinically significant COPD who may benefit from initiation of COPD treatment.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01880177; URL:
www.clinicaltrials.gov.
PMID- 28414032
TI - Rebuttal From Dr Perez et al.
PMID- 28414033
TI - COUNTERPOINT: Are Advanced Practice Professionals More Likely to Achieve Better
Tobacco Cessation Results than Physicians? No.
PMID- 28414034
TI - Age exacerbates surgery-induced cognitive impairment and neuroinflammation in
Sprague-Dawley rats: the role of IL-4.
AB - Age is the most prominent risk factor for the development of postoperative
cognitive dysfunction. This study investigated the potential role of anti
inflammatory interleukin (IL)-4 in age-related differences of surgery-induced
cognitive deficits and neuroinflammatory responses. Both adult and aged Sprague
Dawley male rats were subjected to partial hepatectomy or partial hepatectomy
with a cisterna magna infusion of IL-4. On postoperative days 1, 3, and 7, the
rats were subjected to a reversed Morris water maze test. Hippocampal IL-1beta,
IL-6, IL-4, and IL-4 receptor (IL-4R) were measured at each time point. Brain
derived neurotrophic factor (BDNF), synaptophysin, Ionized calcium-binding
adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, and CD200 were
also examined in the hippocampus. Age induced an exacerbated cognitive impairment
and an amplified neuroinflammatory response triggered by surgical stress on
postoperative days 1 and 3. A corresponding decline in the anti-inflammatory
cytokine IL-4 and BDNF were also found in the aged rats at the same time point.
Treatment with IL-4 downregulated the expression of proinflammatory cytokines
(e.g., IL-1beta and IL-6), increased the levels of BDNF and synaptophysin in the
brain and improved the behavioral performance. An increased Arg1 expression and a
high level of CD200 were also observed after a cisterna magna infusion of IL-4.
An age-related decrease in IL-4 expression exacerbated surgery-induced cognitive
deficits and exaggerated the neuroinflammatory responses. Treatment with IL-4
potentially attenuated these effects by enhancing BDNF and synaptophysin
expression, inhibiting microglia activation and decreasing the associated
production of proinflammatory cytokines.
PMID- 28414035
TI - Bothrops jararaca venom gland secretory cells in culture: Effects of
noradrenaline on toxin production and secretion.
AB - Primary culture of snake venom gland secretory cells could be a good model to
study the mechanism(s) of toxin(s) production. These cells can produce and
secrete venom to the medium with a hemorrhagic activity comparable to that
induced by venom collected from snakes. Production of new venom is triggered by
the sympathetic outflow, through the release of noradrenaline, but the importance
of this neurotransmitter on toxin synthesis has not been addressed. This work led
to the identification and comparison of the toxin panel produced by cultured
secretory cells, during a 12-day time-course analysis, as well as to the effects
of noradrenaline on the process. The results showed that in our culture model the
synthesis of new toxins is asynchronous, mimicking data previously published from
proteomic analyses of venom glands harvested from animal experimentation.
Furthermore, noradrenaline did regulate the synthesis and/or secretion of venom
toxins over the analyzed period. Finally, we demonstrated that snake venom
metalloproteinases present in these cultured cells secretome were mostly in their
zymogen forms; consequently, processing occurs after secretion to the gland
lumen. Overall, the data support the use of venom gland secretory cells as a
reliable model to investigate the mechanism(s) of toxin(s) synthesis and
secretion.
PMID- 28414036
TI - Blunted cortisol response to acute pre-learning stress prevents misinformation
effect in a forced confabulation paradigm.
AB - Research examining the effects of stress on false memory formation has been
equivocal, partly because of the complex nature of stress-memory interactions. A
major factor influencing stress effects on learning is the timing of stress
relative to encoding. Previous work has shown that brief stressors administered
immediately before learning enhance long-term memory. Thus, we predicted that
brief stress immediately before learning would decrease participants'
susceptibility to subsequent misinformation and reduce false memory formation.
Eighty-four male and female participants submerged their hand in ice cold
(stress) or warm (no stress) water for 3min. Immediately afterwards, they viewed
an 8-min excerpt from the Disney movie Looking for Miracles. The next day,
participants were interviewed and asked several questions about the video, some
of which forced them to confabulate responses. Three days and three weeks later,
respectively, participants completed a recognition test in the lab and a free
recall test via email. Our results revealed a robust misinformation effect,
overall, as participants falsely recognized a significant amount of information
that they had confabulated during the interview as having occurred in the
original video. Stress, overall, did not significantly influence this
misinformation effect. However, the misinformation effect was completely absent
in stressed participants who exhibited a blunted cortisol response to the stress,
for both recognition and recall tests. The complete absence of a misinformation
effect in non-responders may lend insight into the interactive roles of autonomic
arousal and corticosteroid levels in false memory development.
PMID- 28414038
TI - Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by
marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation.
AB - Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant
associated infections. Extracellular polymeric substance (EPS) is a key component
of most biofilms and in pathogens it specifically protects the entrenched
bacterial cells from antibiotics and hosts immune response, and thereby makes the
infection ineradicable. Recently, the prominence of cyclic dipeptides in
interfering with biofilms and the associated virulence factors of pathogens has
offered an alternative to eliminate difficult-to-treat infections. Therefore, we
assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l
leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. The non
bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed
through quantitative (crystal violet and XTT assays) and qualitative (confocal
and scanning electron microscopes) analyses. Notably, CLP was potent enough to
reduce all the EPS components viz. polysaccharides, proteins and eDNA to a
significant level. Substantial difference in the atomic composition and
functionality of CLP treated EPS was evident through X-ray photoelectron
spectroscopy. Furthermore, CLP dehydrated the S. epidermidis-EPS and altered the
acetylated sugars as well as alpha-glycosidic linkage in it. The results of
cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS
upon CLP treatment, which goes well in accordance with the decrease of eDNA.
Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic
functional groups and charge of secreted EPS.
PMID- 28414039
TI - Authors' Reply to Rady and Verheijde.
PMID- 28414037
TI - Spatio-temporal regulation of connexin43 phosphorylation and gap junction
dynamics.
AB - Gap junctions are specialized membrane domains containing tens to thousands of
intercellular channels. These channels permit exchange of small molecules
(<1000Da) including ions, amino acids, nucleotides, metabolites and secondary
messengers (e.g., calcium, glucose, cAMP, cGMP, IP3) between cells. The common
reductionist view of these structures is that they are composed entirely of
integral membrane proteins encoded by the 21 member connexin human gene family.
However, it is clear that the normal physiological function of this structure
requires interaction and regulation by a variety of proteins, especially kinases.
Phosphorylation is capable of directly modulating connexin channel function but
the most dramatic effects on gap junction activity occur via the organization of
the gap junction structures themselves. This is a direct result of the short half
life of the primary gap junction protein, connexin, which requires them to be
constantly assembled, remodeled and turned over. The biological consequences of
this remodeling are well illustrated during cardiac ischemia, a process wherein
gap junctions are disassembled and remodeled resulting in arrhythmia and
ultimately heart failure. This article is part of a Special Issue entitled: Gap
Junction Proteins edited by Jean Claude Herve.
PMID- 28414040
TI - SARS coronavirus papain-like protease up-regulates the collagen expression
through non-Samd TGF-beta1 signaling.
AB - SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the
production of TGF-beta1 through p38 MAPK/STAT3-meidated Egr-1-dependent
activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro
induced TGF-beta1 with the expression of Type I collagen in human lung epithelial
cells and mouse pulmonary tissues. Specific inhibitors for TGF-betaRI, p38 MAPK,
MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-beta1-dependent up
regulation of Type I collagen in vitro and in vivo. Subcellular localization
analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-beta1
signaling involved in the production of Type I collagen in transfected cells with
pSARS-PLpro. Comprehensive analysis of ubiquitin-conjugated proteins using
immunoprecipitation and nanoLC-MS/MS indicated that SARS-CoV PLpro caused the
change in the ubiquitination profile of Rho GTPase family proteins, in which
linked with the increase of Rho-like GTPase family proteins. Moreover, selective
inhibitors TGF-betaRI and STAT6 (AS1517499) ascertained that STAT6 activation was
required for PLpro-induced TGF-beta1-dependent up-regulation of Type I collagen
in human lung epithelial cells. The results showed that SARS-CoV PLpro stimulated
TGF-beta1-dependent expression of Type I collagen via activating STAT6 pathway.
PMID- 28414041
TI - Acute and sub-acute toxicological evaluation of lyophilized Nymphaea x rubra
Roxb. ex Andrews rhizome extract.
AB - Nymphaea x rubra Roxb. ex Andrews (N. rubra) has been widely reported for
immunomodulatory properties and treatment of piles, bleeding nose and dysentery
in traditional medicinal systems. However, its in-vitro and in-vivo toxicity
studies have never been investigated. So, the present study was designed to
investigate in-vitro and in-vivo toxicity of methanolic extract of N. rubra
rhizome in rats. In-vitro cytotoxicity studies were conducted for different doses
of extract in N2a cell lines. For in-vivo toxicity studies, SD rats were divided
into three groups and administered with 0, 300 and 2000 mg/kg b. w., p. o., of N.
rubra extract respectively. In acute toxicity studies, female animals after
extract administration animals were sacrificed for hematological profiling and
gross necropsy. In sub-acute toxicity studies, both male and female animals were
administered with extract daily for 14 days and were sacrificed for
hematological, biochemical and histological examination. Body weight and food
water intake was measured daily and animals were observed for visual toxic
effects, behavioral changes and mortality. During in-vivo toxicity studies, none
of the animals showed signs of toxicity and mortality during toxicity studies.
The present findings suggest its safety and NOAEL of N. rubra rhizome extract to
be > 2000 mg/kg b. w.
PMID- 28414042
TI - Promising technological innovations in cognitive training to treat eating-related
behavior.
AB - One potential reason for the suboptimal outcomes of treatments targeting
appetitive behavior, such as eating and alcohol consumption, is that they do not
target the implicit cognitive processes that may be driving these behaviors. Two
groups of related neurocognitive processes that are robustly associated with
dysregulated eating and drinking are attention bias (AB; selective attention to
specific stimuli) and executive function (EF; a set of cognitive control
processes such as inhibitory control, working memory, set shifting, that govern
goal-directed behaviors). An increasing body of work suggests that EF and AB
training programs improve regulation of appetitive behaviors, especially if
trainings are frequent and sustained. However, several key challenges, such as
adherence to the trainings in the long term, and overall potency of the training,
remain. The current manuscript describes five technological innovations that have
the potential to address difficulties related to the effectiveness and
feasibility of EF and AB trainings: (1) deployment of training in the home, (2)
training via smartphone, (3) gamification, (4) virtual reality, and (5)
personalization. The drawbacks of these innovations, as well as areas for future
research, are also discussed. The above-mentioned innovations are likely to be
instrumental in the future empirical work to develop and evaluate effective EF
and AB trainings for appetitive behaviors.
PMID- 28414044
TI - The Impact of the Medicare Access and CHIP Reauthorization Act on the Field of
Ophthalmology.
AB - PURPOSE: To analyze the impact of the Medicare Access and CHIP Reauthorization
Act of 2015 (MACRA) on the field of ophthalmology. DESIGN: A perspective on the
effects of MACRA's Quality Payment Program after analysis of the proposed rule,
final rule, and commentary submitted by relevant stakeholders. RESULTS:
Physicians will need to use 1 of 2 payment structures: Merit-Based Incentive
Payment Systems (MIPS) or Alternative Payment Models (APMs). APMs and MIPS will
focus on bundling payments and reimbursing based on "fee-for-service-plus"
models, which take into account clinical outcomes, coordination of care, clinical
improvement, and electronic information exchange and security. APMs have
substantial advantages, with eligible participants receiving a bonus and a higher
rate of annual adjustment over the program's life. For most ophthalmology
practices, MIPS may be more appropriate owing to its broader applicability and
the current paucity of APMs for ophthalmologists. CONCLUSION: The Quality Payment
Program is a substantial improvement over the negative adjustments under the
repealed Substantial Growth Rate model. Ophthalmologists will likely use the MIPS
system; however, its comparatively lower reimbursements, as well as its cost,
quality, and other reporting measures, may prove problematic.
PMID- 28414043
TI - Quality-of-Life Outcomes From a Randomized Clinical Trial Comparing
Antimetabolites for Intermediate, Posterior, and Panuveitis.
AB - PURPOSE: To evaluate the changes in quality of life in noninfectious uveitis
patients treated with 2 of the most commonly prescribed antimetabolite
treatments. DESIGN: Secondary analysis of a multicenter, block-randomized
clinical trial. METHODS: Eighty patients at Aravind Eye Hospitals in Madurai and
Coimbatore, India, with noninfectious intermediate, posterior, or panuveitis were
randomized to receive oral methotrexate, 25 mg weekly, or oral mycophenolate
mofetil, 1 g twice daily, and were followed up monthly for 6 months. Best
corrected visual acuity, Indian Vision Function Questionnaire (IND-VFQ), and
Medical Outcomes Study 36-item Short Form Survey (SF-36) were obtained at
enrollment and at 6 months (or prior, in the event of early treatment failure).
RESULTS: IND-VFQ scores, on average, increased by 9.2 points from trial
enrollment to 6 months (95% confidence interval [CI]: 4.9, 13.5, P = .0001).
Although the SF-36 physical component summary score did not significantly differ
over the course of the trial, the mental component summary score decreased by 2.3
points (95% CI: -4.4, -0.1, P = .04) and the vitality subscale decreased by 3.5
points (95% CI: -5.6, -1.4, P = .001). Quality-of-life scores did not differ
between treatment arms. Linear regression modeling showed a 3.2-point improvement
in IND-VFQ score for every 5-letter improvement in visual acuity (95% CI: 1.9,
4.3; P < .001). CONCLUSIONS: Although uveitis treatment was associated with
increased vision and vision-related quality of life, patient-reported physical
health did not change after 6 months of treatment, and mental health decreased.
Despite improved visual outcomes, uveitis patients receiving systemic
immunosuppressive therapy may experience a deterioration in mental health-related
quality of life.
PMID- 28414045
TI - Viscosities encountered during the cryopreservation of dimethyl sulphoxide
systems.
AB - This study determined the viscous conditions experienced by cells in the unfrozen
freeze concentrated channels between ice crystals in slow cooling protocols. This
was examined for both the binary Me2SO-water and the ternary Me2SO-NaCl-water
systems. Viscosity increases from 6.9 +/- 0.1 mPa s at -14.4 +/- 0.3 degrees C
to 958 +/- 27 mPa s at -64.3 +/- 0.4 degrees C in the binary system, and up to
55387 +/- 1068 mPa s at -75 +/- 0.5 degrees C in the ternary (10% Me2SO, 0.9%
NaCl by weight) solution were seen. This increase in viscosity limits molecular
diffusion, reducing adsorption onto the crystal plane. These viscosities are
significantly lower than observed in glycerol based systems and so cells in
freeze concentrated channels cooled to between -60 degrees C and -75 degrees C
will reside in a thick fluid not a near-solid state as is often assumed. In
addition, the viscosities experienced during cooling of various Me2SO based
vitrification solutions is determined to below -70 degrees C, as is the impact
which additional solutes exert on viscosity. These data show that additional
solutes in a cryopreservation system cause disproportionate increases in
viscosity. This in turn impacts diffusion rates and mixing abilities of high
concentrations of cryoprotectants, and have applications to understanding the
fundamental cooling responses of cells to Me2SO based cryopreservation solutions.
PMID- 28414046
TI - Caffeoyl and coumaroyl derivatives from Acacia cochliacantha exhibit ovicidal
activity against Haemonchus contortus.
AB - ETHNOPHARMACOLOGY RELEVANCE: Acacia cochliacantha is a small tree whose foliage
is traditionally used in Mexico for treatment of kidney pain, gastrointestinal
illnesses and to kill intestinal parasites. In recent decades, the study of
vegetal extracts has offered other possible alternatives for the control of
Haemonchus contortus. Considering that this nematode affects dramatically the
health and productivity of small ruminants, the aim of this study was to identify
the anthelmintic compounds from A. cochliacantha hydro-alcoholic extract (HA-E)
through an ovicidal test. MATERIAL AND METHODS: In vitro egg hatch assay was
conducted to determinate the anthelmintic effects of a HA-E (60g). Liquid-liquid
ethyl acetate/water extraction gave two fractions (EtOAc-F, 1.92g; Aq-F; 58.1g).
The less polar compounds from ethyl acetate fraction were extracted by addition
of dichloromethane offering a precipitate phase (Mt-F, 1.25g) and a soluble
mixture (DCMt-F 1.15g). All fractions were evaluated for ovicidal activity
obtaining the egg hatching inhibition (EHI, 0.07-25mg/mL). Ivermectin (0.5mg/mL)
was used as a reference drug (positive control), and distilled water, 2.5% DMSO
and 2% methanol were used as negative controls. The isolated compounds from the
most active fractions were subjected to spectroscopic (1H NMR) Spectrometric (MS)
and UV HPLC analysis in order to identify the bioactive compounds. RESULTS: The
less polar treatments (AcOEt-F, DCMt-F, DCMt-P) showed the highest ovicidal
activities (98-100% EHI; at 0.62-1.56mg/mL) and the major compounds found in
these fractions were identified as caffeoyl and coumaroyl derivatives, including
caffeic acid (1), p-coumaric acid (2), ferulic acid (3), methyl caffeate (4),
methyl-p-coumarate (5), methyl ferulate (6) and quercetin. In case of the less
active fractions (Aq-F, Mt-F) were constituted principally by glycosylated
flavonoids. CONCLUSION: These results show that caffeoyl and coumaroyl
derivatives from Acacia cochliacantha leaves had promising anthelmintic activity
against Haemonchus contortus. This leguminous may offer an alternative source for
the control of gastrointestinal nematodes of small ruminants.
PMID- 28414047
TI - A novel automated rodent tracker (ART), demonstrated in a mouse model of
amyotrophic lateral sclerosis.
AB - BACKGROUND: Generating quantitative metrics of rodent locomotion and general
behaviours from video footage is important in behavioural neuroscience studies.
However, there is not yet a free software system that can process large amounts
of video data with minimal user interventions. NEW METHOD: Here we propose a new,
automated rodent tracker (ART) that uses a simple rule-based system to quickly
and robustly track rodent nose and body points, with minimal user input. Tracked
points can then be used to identify behaviours, approximate body size and provide
locomotion metrics, such as speed and distance. RESULTS: ART was demonstrated
here on video recordings of a SOD1 mouse model, of amyotrophic lateral sclerosis,
aged 30, 60, 90 and 120days. Results showed a robust decline in locomotion
speeds, as well as a reduction in object exploration and forward movement, with
an increase in the time spent still. Body size approximations (centroid width),
showed a significant decrease from P30. COMPARISON WITH EXISTING METHOD(S): ART
performed to a very similar accuracy as manual tracking and Ethovision (a
commercially available alternative), with average differences in coordinate
points of 0.6 and 0.8mm, respectively. However, it required much less user
intervention than Ethovision (6 as opposed to 30 mouse clicks) and worked
robustly over more videos. CONCLUSIONS: ART provides an open-source option for
behavioural analysis of rodents, performing to the same standards as commercially
available software. It can be considered a validated, and accessible, alternative
for researchers for whom non-invasive quantification of natural rodent behaviour
is desirable.
PMID- 28414049
TI - Spotlight on vitamin D receptor, lipid metabolism and mitochondria: Some
preliminary emerging issues.
AB - Transcriptional control and modulation of calcium fluxes underpin the
differentiating properties of vitamin D (1,25(OH)2D3). In the latest years
however few studies have pointed out the relevance of the mitochondrial effects
of the hormone. It is now time to focus on the metabolic results of vitamin D
receptor (VDR) action in mitochondria, which can explain the pleiotropic effects
of 1,25(OH)2D3 and may elucidate few contrasting aspects of its activity. The
perturbation of lipid metabolism described in VDR knockout mice and vitamin D
deficient animals can be revisited based on the newly identified mechanism of
action of 1,25(OH)2D3 in mitochondria. From the same point of view, the
controversial role of 1,25(OH)2D3 in adipogenesis can be better interpreted.
PMID- 28414048
TI - Light and the laboratory mouse.
AB - Light exerts widespread effects on physiology and behaviour. As well as the
widely-appreciated role of light in vision, light also plays a critical role in
many non-visual responses, including regulating circadian rhythms, sleep, pupil
constriction, heart rate, hormone release and learning and memory. In mammals,
responses to light are all mediated via retinal photoreceptors, including the
classical rods and cones involved in vision as well as the recently identified
melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs).
Understanding the effects of light on the laboratory mouse therefore depends upon
an appreciation of the physiology of these retinal photoreceptors, including
their differing sens itivities to absolute light levels and wavelengths. The
signals from these photoreceptors are often integrated, with different responses
involving distinct retinal projections, making generalisations challenging.
Furthermore, many commonly used laboratory mouse strains carry mutations that
affect visual or non-visual physiology, ranging from inherited retinal
degeneration to genetic differences in sleep and circadian rhythms. Here we
provide an overview of the visual and non-visual systems before discussing
practical considerations for the use of light for researchers and animal facility
staff working with laboratory mice.
PMID- 28414050
TI - A study of time- and sex-dependent effects of vortioxetine on rat sexual
behavior: Possible roles of direct receptor modulation.
AB - Treatment-related sexual dysfunction is a common side effect of antidepressants
and contributes to patient non-compliance or treatment cessation. However, the
multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in
depressed patients. To investigate the mechanisms involved, sexual behavior was
assessed in male and female rats after acute, and repeated (7 and 14 days)
treatment with vortioxetine, flesinoxan (a 5-HT1A receptor agonist), CP-94253 (a
5-HT1B receptor agonist), or ondansetron (a 5-HT3 receptor antagonist). These
selective ligands were chosen to simulate vortioxetine's direct modulation of
these receptors. Paroxetine was also included in the male study. Acute and
repeated treatment with vortioxetine at doses corresponding to clinical levels
(based on serotonin transporter occupancy) had minimal effects on sexual behavior
in male and female rats. High dose vortioxetine plus flesinoxan (to mimic
predicted clinical levels of 5-HT1A receptor occupancy by vortioxetine)
facilitated male rat sexual behavior (acutely) while inhibiting female rat
proceptive behavior (both acutely and after 14 days treatment). The selective
serotonin reuptake inhibitor, paroxetine, inhibited male sexual behavior after
repeated administration (7 and 14 days). Flesinoxan alone facilitated male sexual
behavior acutely while inhibiting female rat proceptive behavior after repeated
administration (7 and 14 days). CP-94253 inhibited sexual behavior in both male
and female rats after repeated administration. Ondansetron had no effect on
sexual behavior. These findings underline the complex serotonergic regulation of
sexual behavior and indicate that the low sexual side effects of vortioxetine
found in clinical studies are likely associated with its direct modulation of
serotonin receptors.
PMID- 28414052
TI - Spiral MR fingerprinting at 7T with simultaneous B1 estimation.
AB - Magnetic resonance fingerprinting is an efficient, new approach for quantitative
imaging with MR. We aimed to extend this technique to cases with B1+
inhomogeneities within the imaging volume. Previous approaches have used abrupt
changes in flip angles to estimate the B1+ field simultaneously with T1 and T2,
using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated
whether a similar approach would be suitable for imaging human brains using
spiral readouts with a 7T scanner. We found that our modified scheme could
significantly reduce the adverse effects of B1+ inhomogeneities even in extreme
cases, reducing both the bias and the variance in T2 estimations by an order of
magnitude when compared to literature methods. Acquisitions used less than
1.5W/kg SAR and could be performed in 12s per slice. In conclusion, our approach
can be used to perform quantitative imaging of the brain at 7T in a short time,
simultaneously estimating the B1+ profile.
PMID- 28414051
TI - Mechanisms contributing to cognitive deficits in cannabis users.
AB - Studies from preclinical animal models indicate that sustained activation of CB1
receptor signaling is a major contributing factor for the onset of cognitive
deficits associated to chronic cannabis use, in particular within the working
memory and decision-making domains. Yet, very few studies have been designed to
directly assess the role of CB1 receptors in mediating the effects of cannabis on
human brain function. This perspective review article provides an overview of
current state of knowledge on possible neurobiological mechanisms accounting for
the detrimental effects of chronic cannabis use on cognition and related changes
in brain structure and functional connectivity. This article is part of the
Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".
PMID- 28414053
TI - Inhibition effects of novel polyketide compound PPQ-B against influenza A virus
replication by interfering with the cellular EGFR pathway.
AB - Development of anti-influenza A virus (IAV) drugs with novel targets and low
toxicity is critical for preparedness against influenza outbreaks. In the current
study, our results indicated that the novel polyketide compound purpurquinone B
(PPQ-B) derived from acid-tolerant fungus Penicillium purpurogenum strain JS03-21
suppressed the replication of IAV in vitro with low toxicity, and may block some
stages after virus adsorption. PPQ-B could inhibit H1N1 (A/Puerto Rico/8/34;
PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009)
virus replication in vitro, suggesting that PPQ-B possesses broad-spectrum anti
IAV activities. PPQ-B's antiviral activity may be largely related to its
inhibition of some steps that occur 0-4 h after adsorption. Oral administration
of PPQ-B could decrease pulmonary viral titers and improve survival rate in IAV
infected mice. PPQ-B also significantly decreased the production of inflammatory
factors TNF-alpha, IL-6, RANTES and KC in IAV infected lungs and A549 cells,
suggesting that PPQ-B may also attenuate the inflammatory responses caused by IAV
infection. PPQ-B may down-regulate the NF-kappaB and MAPK pathways to inhibit
both virus replication and inflammatory responses. In summary, PPQ-B has the
potential to be developed into a novel anti-IAV drug targeting host EGFR pathway
in the future.
PMID- 28414054
TI - Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal
mammary artery.
AB - The aim of the present study was to investigate and characterize vasorelaxant
effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the
mechanisms of its protective effect against vascular risk. Procyanidin B2 induced
strong concentration-dependent relaxation of HIMA rings pre-contracted by
phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor,
hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate
cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while
indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low
concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of
large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2
induced relaxation, glibenclamide, a selective ATP-sensitive K+(KATP) channels
blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage
gated K+(KV) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+
activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA.
Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free
Krebs solution, but had no effect on contraction induced by caffeine. Finally,
thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly
reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate
that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre
contracted by phenylephrine. This effect is primarily the result of an increased
NO synthesis and secretion by endothelial cells and partially of prostacyclin,
although it involves activation of BKCa and KATP, as well as KV and IKCa channels
in high concentrations of procyanidin B2.
PMID- 28414055
TI - Dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation
related to inhibitory of oxidative stress.
AB - Dihydromyricetin (DMY) is one of the most important flavonoids in vine tea, which
showed several pharmacological effects. However, information about the potential
role of DMY on angiotensin II (Ang II) induced cardiac fibroblasts proliferation
remains unknown. In the present study, cardiac fibroblasts isolated from neonatal
Sprague-Dawley rats were pretreated with different concentrations of DMY (0
320MUM) for 4h, or DMY (80MUM) for different time (0-24h), followed by Ang II
(100nM) stimulation for 24h, Then number of cardiac fibroblasts and content of
hydroxyproline was measured. The level of cellular reactive oxygen species,
malondialdehyde (MDA), activity of superoxide dismutase (SOD) and total
antioxidant capacity (T-AOC) were also evaluated. Expression of type I, type III
collagen, alpha-smooth muscle actin (alpha-SMA), p22phox (one vital subunit of
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase), SOD and thioredoxin
(Trx) were detected with real time PCR or/and western blot. We found that pre
incubation with DMY (20MUM, 40MUM, 80MUM) for 4h, 12h or 24h attenuated the
proliferation of cardiac fibroblasts induced by Ang II. Expression of type I and
type III collagen, as well as alpha-SMA were inhibited by DMY at both mRNA and
protein level. DMY also significantly decreased cellular reactive oxygen species
production and MDA level, while increased the SOD activity and T-AOC. DMY
suppressed p22phox, while enhanced antioxidant SOD and Trx expression in Ang II
stimulated cardiac fibroblasts. Thus, dihydromyricetin attenuated Ang II induced
cardiac fibroblasts proliferation related to inhibitory of oxidative stress.
PMID- 28414056
TI - Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease
in mice.
AB - Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death
from many diseases. The purpose of the present study is to investigate the
protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on
NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the
mechanisms underlying GA protection. GA treatment significantly reduced the
relative liver weight, serum ALT, AST activities, levels of serum lipid, blood
glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism
investigation indicated that GA reduced hepatic lipogenesis via downregulating
SREBP-1c, FAS and SCD1 expression, increased fatty acids beta-oxidation via an
increase in PPARalpha, CPT1alpha and ACADS, and promoted triglyceride metabolism
through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through
repressing PEPCK and G6Pase, and increased glycogen synthesis through an
induction in gene expression of PDase and GSK3beta. In addition, GA increased
insulin sensitivity through upregulating phosphorylation of IRS-1 and IRS-2. In
conclusion, GA produces protective effect against NAFLD, due to regulation of
genes involved in lipid, glucose homeostasis and insulin sensitivity.
PMID- 28414057
TI - Non-invasive assessment of liver fibrosis in patients with HBV-related chronic
liver disease undergoing antiviral treatment: A preliminary study.
AB - In chronic hepatitis B (CHB) patients, fibrosis assessment during antiviral
treatment is a key step in the clinical management. Aim of this study was to
evaluate the performance of elastography in assessing fibrosis stage in CHB
before and after two years of nucleoside/nucleotide analogues (NUC) treatment in
comparison with indirect serum markers. CHB diagnosis was made according to
standard criteria. A clinical and virological evaluation was performed at
baseline and again at 3, 6, 9, 12 18, and 24 months during treatment. Fibrosis
was evaluated by liver biopsy, elastography and indirect serum markers. Of 75
patients, 50 had CHB, HBeAg negative and were deemed eligible for this study. Of
these, 22 underwent liver biopsy. Mean histo-morphometric values of fibrotic
tissue differed significantly in the stage < S3 vs. stage >=S3: 2.01+/-2.62% vs.
12.85+/-7.31% (p=0.03), respectively. At 18 and 24 months, stiffness values were
statistically reduced from those previously observed (P=0.03 and P<0.001). At 24
months the values of APRI, FIB-4 and LOK were not different from baseline values,
while the value of FORNS score at 24 months was the only one statistically
reduced. In two patients with fibrosis stage S3 and S6, respectively, fibrosis
regressed to stage S2 and S5. In conclusion, the results of the present study
show that liver histology, stiffness and FORNS score improve significantly during
a long-term follow-up of HBV patients successfully treated with NUC. These
results strongly suggest that the non-invasive evaluation of liver fibrosis
represents a key step in the management and treatment of chronic HBV hepatitis.
PMID- 28414058
TI - Assessment of bone turnover markers to predict mineral and bone disorder in men
with pre-dialysis non-diabetic chronic kidney disease.
AB - BACKGROUND: Chronic kidney disease (CKD) is commonly associated with disturbances
in mineral metabolism and bone disease. Bone biopsy is the gold standard in
diagnosing mineral bone disorder. Hence the search for non-invasive assessment of
bone health gains importance. We undertook to assess the bone health in men with
stage 4 and 5 chronic kidney Disease. METHODS: We recruited 32 male subjects with
Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25
hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline
phosphatase were assayed. Bone mineral density (BMD) was estimated using dual
energy X-ray absorptiometry. RESULTS: CKD is associated with significantly higher
levels of bone-specific alkaline phosphatase and intact parathyroid hormone and
lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to
controls. In the multivariate linear regression model, bone-specific alkaline
phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator
Characteristic analysis for prediction of reduced BMD in CKD showed both intact
parathyroid hormone and bone-specific alkaline phosphatase have significant
predicting power. CONCLUSION: The combination of bone-specific alkaline
phosphatase and intact parathyroid hormone has more significant predicting power
and is a more reliable index for non-invasive assessment of bone health in men
with chronic kidney disease, than either marker when used alone.
PMID- 28414059
TI - A mouse ocular explant model that enables the study of living optic nerve head
events after acute and chronic intraocular pressure elevation: Focusing on
retinal ganglion cell axons and mitochondria.
AB - We developed an explant model of the mouse eye and optic nerve that facilitates
the study of retinal ganglion cell axons and mitochondria in the living optic
nerve head (ONH) in an ex vivo environment. Two transgenic mouse strains were
used, one expressing yellow fluorescent protein in selected axons and a second
strain expressing cyan fluorescent protein in all mitochondria. We viewed an
explanted mouse eye and optic nerve by laser scanning microscopy at and behind
the ONH, the site of glaucoma injury. Explants from previously untreated mice
were studied with the intraocular pressure (IOP) set artificially at normal or
elevated levels for several hours. Explants were also studied from eyes that had
undergone chronic IOP elevation from 14 h to 6 weeks prior to ex vivo study.
Image analysis in static images and video of individual mitochondria or axonal
structure determined effects of acute and chronic IOP elevation. At normal IOP,
fluorescent axonal structure was stable for up to 3 h under ex vivo conditions.
After chronic IOP elevation, axonal integrity index values indicated
fragmentation of axon structure in the ONH. In mice with fluorescent
mitochondria, the normal density decreased with distance behind the ONH by 45% (p
= 0.002, t-test). Density increased with prior chronic IOP elevation to 21,300 +/
4176 mitochondria/mm2 compared to control 16,110 +/- 3159 mitochondria/mm2 (p =
0.025, t-test), but did not increase significantly after 4 h, acute IOP elevation
(1.5% decrease in density, p = 0.83, t-test). Mean normal mitochondrial length of
2.3 +/- 1.4 MUm became 13% smaller after 4 h of IOP elevation ex vivo compared to
baseline (p = 0.015, t-test, N-10). Normal mitochondrial speed of movement was
significantly slower in the anterograde direction (towards the brain) than
retrograde, but there were more mitochondria in motion and traveling longer
lengths in anterograde direction. The percent of mitochondria in motion decreased
by >50% with acute IOP increase to 30 mm Hg after 60 min. A new ocular explant
model implemented with eyes from transgenic mice with fluorescent cellular
components provided real time measurement of the early events in experimental
glaucoma and quantitative outcomes for neuroprotection therapy experiments.
PMID- 28414060
TI - Dietary protein content alters both male and female contributions to Drosophila
melanogaster female post-mating response traits.
AB - Males transfer sperm, proteins and other molecules to females during mating. In
Drosophila melanogaster, these molecules contribute to the induction of egg
maturation, ovulation, oviposition, sperm storage and changes in female
receptivity. This suite of physiological and behavioral changes is referred to as
the female post-mating response (PMR). Protein is a necessary macronutrient for
both male and female reproduction, but imbalances in protein content can decrease
reproductive potential. Dietary protein affects the production of proteins in the
male ejaculate that are important for induction of the PMR, and female fecundity
increases with dietary protein while lifetime mating rate decreases. The effects
of dietary protein levels on other aspects of the female PMR and on male ability
to induce the PMR are unknown. To investigate how protein content affects PMR, we
raised flies on diets containing low, moderate or high levels of protein and
mated females and males from each diet in a combinatorial manner. We first
measured the mating duration for each pair, an indication of male reproductive
investment, and then evaluated two aspects of the female PMR, fecundity and
female remating latency. We found that mating duration was negatively correlated
with male dietary protein, and females that mated with high protein males laid
fewer eggs. Female diet had no effect on mating duration, but females fed diets
with higher protein content laid more eggs and remated sooner. Therefore, dietary
protein levels can affect postcopulatory processes important for reproductive
output in a sexually dimorphic manner.
PMID- 28414062
TI - Novel PIK3CD mutations affecting N-terminal residues of p110delta cause activated
PI3Kdelta syndrome (APDS) in humans.
PMID- 28414061
TI - Mechanistic correlates of clinical responses to omalizumab in the setting of oral
immunotherapy for milk allergy.
AB - BACKGROUND: In our recent clinical trial, the addition of omalizumab to oral
immunotherapy (OIT) for milk allergy improved safety, but no significant clinical
benefit was detected. OBJECTIVE: We sought to investigate mechanisms by which
omalizumab modulates immunity in the context of OIT and to identify baseline
biomarkers that predict subgroups of patients most likely to benefit from
omalizumab. METHODS: Blood was obtained at baseline and multiple time points
during a placebo-controlled trial of OIT for milk allergy in which subjects were
randomized to receive omalizumab or placebo. Immunologic outcomes included
measurement of basophil CD63 expression and histamine release and casein-specific
CD4+ regulatory T-cell proliferation. Biomarkers were analyzed in relationship to
measurements of safety and efficacy. RESULTS: Milk-induced basophil CD63
expression was transiently reduced in whole blood samples from both omalizumab-
and placebo-treated subjects. However, IgE-dependent histamine release increased
in washed cell preparations from omalizumab- but not placebo-treated subjects. No
increase in regulatory T-cell frequency was evident in either group. Subjects
with lower rates of adverse reactions, regardless of arm, experienced better
clinical outcomes. Pre-OIT basophil reactivity positively associated with
occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio
correlated with the likelihood of achieving sustained unresponsiveness. A
combination of baseline basophil and serologic biomarkers defined a subset of
patients in which adjunctive therapy with omalizumab was associated with
attainment of sustained unresponsiveness and a reduction in adverse reactions.
CONCLUSIONS: Combining omalizumab therapy with milk OIT led to distinct
alterations in basophil reactivity but not T-cell responses. Baseline biomarkers
can identify subjects most likely to benefit from adjunctive therapy with
omalizumab.
PMID- 28414063
TI - Hypersensitivity transfusion reactions due to IgA deficiency are rare according
to French hemovigilance data.
PMID- 28414064
TI - Obesity in coronary heart disease: An unaddressed behavioral risk factor.
AB - Obesity is an independent risk factor for the development and progression of
coronary heart disease (CHD). Over 80% of patients with CHD are overweight or
obese. While obesity is often considered a relatively "minor" CHD risk factor,
weight loss is a broadly effective risk-factor intervention. Weight loss can
profoundly influence a number of "major" risk factors including: hypertension,
dyslipidemia and insulin resistance/type 2 diabetes mellitus. Despite its
prominence as a risk factor most cardiac rehabilitation (CR) programs do not have
a specific, targeted intervention to assist patients with weight loss.
Consequently, the weight loss that occurs during CR is quite small and unlikely
to appreciably alter risk factors. Relying on CR associated exercise as a sole
intervention is an ineffective strategy to promote weight loss. There is
evidence, however, that behavioral weight loss (BWL) interventions can be
effectively employed in the CR setting. In contrast to programs that do not offer
a targeted intervention, studies show that participants in CR-related BWL
programs lose significantly more weight. The additional weight loss from the BWL
intervention is associated with greater improvements in insulin sensitivity and
other components of the metabolic syndrome such as hypertension and lipid
abnormalities. As a means of maximizing CHD risk factor reduction CR programs
need to incorporate BWL programs as a standard programming for overweight/obese
patients.
PMID- 28414065
TI - Effects of depression screening on diagnosing and treating mood disorders among
older adults in office-based primary care outpatient settings: An instrumental
variable analysis.
AB - Existing literature shows mixed findings regarding the efficacy and effectiveness
of depression screening, and relatively little is known about the effectiveness
of depression screening among older adults in primary care visits in the U.S.
This study examines the effects of depression screening on the three following
outcomes: mood disorder diagnoses, overall antidepressant prescriptions, and
potentially inappropriate antidepressant prescriptions among older adults ages 65
or older in office-based outpatient primary care settings. We used data from 2010
2012 National Ambulatory Medical Care Survey (NAMCS), a nationally representative
sample of office-based primary care outpatient visits among older adults (n=9,313
unweighted). We employed an instrumental variable approach to control for
selection bias in our repeated cross-sectional population-based study. Injury
prevention and stress management were selected as instrumental variables, as they
were considered completely exogenous to outcomes of interests using conceptual
and statistical criteria. We conducted multivariate bivariate probit (biprobit)
regression analyses to investigate the effect of depression screening on each
outcome, when controlled for other covariates. We found that depression screening
was negatively associated with potentially inappropriate antidepressant
prescriptions (beta=-2.17; 95% CI -2.80 to -1.53; p<0.001). However, no
significant effect of depression screening on diagnosis of mood disorders and
overall antidepressant prescriptions was found. Overall, depression screening had
a negative effect on potentially inappropriate antidepressant prescriptions.
Primary care physicians and other healthcare providers should actively utilize
depression screening to minimize potentially inappropriate antidepressant
prescriptions in older adult patients.
PMID- 28414066
TI - Factors associated with maintenance of body mass index in the Jackson Heart
Study: A prospective cohort study secondary analysis.
AB - The purpose of this study was to compare the relationship of diet quality,
physical activity, and environmental factors with body mass index (BMI)
maintenance in African American adults. We analyzed data from 4041 participants
in the Jackson Heart Study, a prospective cohort study based in Jackson,
Mississippi. Exposures were baseline American Heart Association diet quality
score, American Heart Association physical activity categories, the built
environment, the food environment, and neighborhood safety. The outcome was
weight maintenance or loss (no BMI increase >=1.0kg/m2) versus weight gain (BMI
increased >=1.0kg/m2) over a mean of 5.0years. We found that 63% of participants
maintained or lost weight and 37% gained weight. In multivariable analyses, ideal
diet quality was associated with a 6% greater likelihood of BMI maintenance
(incidence rate ratio [IRR] 1.06, 95% confidence interval [CI]: 1.03, 1.10).
Living in an unsafe neighborhood was associated with a 2% lower likelihood of BMI
maintenance (IRR 0.98, 95% CI: 0.96, 0.99), as was poor built environment (IRR
0.98, 95% CI: 0.97, 0.998). Physical activity and poor food environment were not
associated with BMI maintenance. In conclusion, among African American adults in
Jackson, Mississippi, high quality diet was the strongest factor associated with
BMI maintenance.
PMID- 28414067
TI - Effective strategies for host cell protein clearance in downstream processing of
monoclonal antibodies and Fc-fusion proteins.
AB - Recombinant therapeutic proteins are typically produced through cell culture
process. Host cell proteins (HCPs) are endogenous proteins derived from the host
cells used for such bioproduction. HCPs form a major class of process-related
impurities and even at low levels they can potentially compromise the safety and
efficacy of biopharmaceuticals. Therefore, they need to be adequately removed via
the downstream process. HCPs are complex mixtures with diverse physiochemical
properties, and certain subpopulations can bind to the intended product. Hence
reducing them to the generally accepted level can be challenging. This article
reviews effective HCP removing strategies at different stages of downstream
process for monoclonal antibodies and Fc-fusion proteins. When used in
combination, these strategies can greatly enhance the chance of meeting the drug
substance specifications for residual HCP.
PMID- 28414068
TI - Modulation of anthraquinones and phloroglucinols biosynthesis in Hypericum spp.
by cryogenic treatment.
AB - Beside the high post-cryogenic recovery rate, a reinstated scale of secondary
metabolites in recovered plant tissues represents another inevitable aspect of an
effective cryopreservation protocol for medicinal plants. The current study was
aimed at evaluation of the elicitation potential of cryogenic treatment on
secondary metabolism of some Hypericum species. In agreement with our assumption,
the cold stimuli applied during the pre-cryogenic phase increased the tolerance
to low temperatures (-196 degrees C) in H. perforatum, H. rumeliacum and H.
tetrapterum reaching a maximum of 46% recovery rate in St. John's wort plants.
The effect of cryogenic treatment-associated stressors on the spectrum of the
profiling secondary metabolites, naphthodianthrones and phloroglucinols, was
ambiguous. The content of hypericins in both pre-cultured H. tetrapterum donor
plants and H. perforatum shoots regenerated from cryopreserved meristems
increased more than 3-times. The highest 38-fold enhancement of phloroglucinols
was observed in H. rumeliacum shoots recovered after cryostorage. Our findings
indicate that modulated biosynthesis of secondary metabolites represented by
naphtodianthrones and phloroglucinols can be considered as a part of overall
plant adaptations to stress conditions associated with liquid nitrogen (LN)
treatment.
PMID- 28414069
TI - Complications associated with antibiotic administration: neurological adverse
events and interference with antiepileptic drugs.
AB - Antibiotic use is associated with toxic effects involving the peripheral and
central nervous systems and it may interfere with antiepileptic drugs, causing
significant variations in their serum levels and activity. Prompt identification
of neurological complications during antibiotic therapy is important in order to
make appropriate modifications to medication. Characteristics of the drug and the
patient, including age and underlying diseases, may favour these complications.
The main aim of this study was to review the neurological adverse events that may
follow antibiotic administration, the mechanisms that cause them, and the
possibility of prevention and treatment. Moreover, the interference of
antibiotics with serum levels and the activity of antiepileptic drugs are
discussed. The results demonstrate that antibiotic-associated adverse events
involving the nervous system are relatively uncommon and are only rarely severe
and irreversible, although neurotoxicity has been reported for several
antibiotics. Moreover, for patients receiving antiepileptic drugs, monitoring of
drug serum levels to avoid the risk of toxicity or inadequate therapy is
mandatory during antibiotic treatment. Areas for future research include the
effects of combined antibiotic therapies as well as multiple antiepileptic drugs
in study populations with an adequate sample size, including neonates and
infants, patients with pharmacoresistant epilepsy and elderly patients.
PMID- 28414070
TI - The unhealthy attraction of Plasmodium vivax to reticulocytes expressing
transferrin receptor 1 (CD71).
AB - The majority of malaria parasite species prefer to invade reticulocytes, the most
infamous being Plasmodium vivax. While the absence of an in vitro continuous
culture method has hampered the study of P. vivax invasion biology, studies
utilising primate models and ex vivo assays have provided some important
insights. Most importantly, P. vivax merozoites have a strong preference for a
subset of immature erythrocytes characterised by the expression of the
transferrin receptor (CD71). This current opinion piece on P. vivax merozoite
invasion highlights important gaps in our understanding of how this parasite
recognises and enters reticulocytes, and discusses some recent conceptual
advances in P. vivax invasion biology.
PMID- 28414071
TI - Epigenetic landscapes underlining global patterns of gene expression in the human
malaria parasite, Plasmodium falciparum.
AB - The dynamic chromatin landscape displaying combinatorial complexity of the
epigenome impacts gene expression that underlies many events of differentiation
and cell cycle progression. In the past few years, epigenetic mechanisms have
emerged as important processes involved in the tight gene regulation in malaria
parasites, Plasmodium spp. Focusing predominantly on Plasmodium falciparum, the
species associated with the most severe form of the disease, many advances have
been made in our understanding of the interaction between transcriptional
regulation and epigenetic mechanisms as the pivotal processes in regulating life
cycle progression, host parasite interactions and parasite adaptation to the host
environment. This review focuses on the epigenome and its effect on
transcriptional regulation in P. falciparum, highlighting its unique,
evolutionary diverse features.
PMID- 28414072
TI - Resistance training is associated with spontaneous changes in aerobic physical
activity but not overall diet quality in adults with prediabetes.
AB - BACKGROUND: Aerobic exercise interventions have been shown to result in
alterations to dietary intake and non-exercise physical activity (PA). To date,
the ability for resistance training (RT) to influence other health-related
behaviors has not been examined. This study aimed to determine if initiation and
maintenance of RT is associated with spontaneous changes in dietary quality and
non-RT PA in adults with prediabetes. METHODS: Overweight/obese adults (n=170,
BMI=32.9+/-3.8kg.m2, age=59.5+/-5.5years, 73% female) with prediabetes were
enrolled in the 15-month Resist Diabetes trial. Participants completed a
supervised 3-month RT initiation phase followed by a 6-month maintenance phase
and a 6-month no-contact phase. Participants were not encouraged to change eating
or non-RT PA behaviors. At baseline, and months 3, 9, and 15, three 24-hour diet
recalls were collected to evaluate dietary intake and quality, the Aerobics
Institute Longitudinal Study Questionnaire was completed to evaluate non-RT PA,
and body mass, body composition (DXA), and muscular strength were measured. At
months 3, 9, and 15 social cognitive theory (SCT) constructs were assessed with a
RT Health Beliefs Questionnaire. Mixed effects models were used to assess changes
in dietary intake and non-RT PA over the 15-month study period. RESULTS: Energy
and carbohydrate intake decreased with RT initiation and maintenance phases
(baseline to month 9: beta=-87.9, p=0.015 and beta=-16.3, p<0.001, respectively).
No change in overall dietary quality (Healthy Eating Index [HEI]-2010 score:
beta=-0.13, p=0.722) occurred, but alterations in HEI-2010 sub-scores were
detected. Maintenance of RT was accompanied by an increase in MET-min/week of
total non-RT PA (month 3 to month 9: beta=146.2, p=0.01), which was predicted by
increased self-regulation and decreased negative outcome expectancies for RT
(beta=83.7, p=0.014 and beta=-70.0, p=0.038, respectively). CONCLUSIONS:
Initiation and maintenance of RT may be a gateway behavior leading to
improvements in other health-related behaviors. These results provide rationale
for single-component lifestyle interventions as an alternative to multi-component
interventions, when resources are limited.
PMID- 28414074
TI - A novel chemotherapy drug-free delivery system composed of three therapeutic
aptamers for the treatment of prostate and breast cancers in vitro and in vivo.
AB - In this study, a novel chemotherapy drug-free DNA nanocomplex composed of three
therapeutic aptamers (IDA, AS1411 and apMNK2F) was designed for treatment of
cancer cells. For MTT assay, PC-3 and 4T1 cells (target cells) and CHO cells
(nontarget cells) were treated with apMNK2F-AS1411-IDA complex (DNA nanocomplex),
as well as AS1411, IDA and apMNK2F alone. Internalization of apMNK2F-AS1411-IDA
complex was analyzed by fluorescence imaging and flow cytometry analysis. In the
last step, the presented DNA nanocomplex was applied for prohibition of tumor
growth in vivo. The results of internalization assay verified that the developed
apMNK2F-AS1411-IDA complex was remarkably internalized into PC-3 and 4T1 cells,
but not into CHO cells. The results of internalization assay was confirmed by MTT
assay. apMNK2F-AS1411-IDA complex was more cytotoxic in PC-3 and 4T1 cells
(target) and less cytotoxic in CHO cells (nontarget). Also, the DNA nanocomplex
could effectively suppress the growth of tumors in vivo.
PMID- 28414075
TI - Vitamin B2 deficiency enhances the pro-inflammatory activity of adipocyte,
consequences for insulin resistance and metabolic syndrome development.
AB - AIMS: Adipose tissue is an endocrine organ important for regulation of such
physiological processes as energy metabolism or lipids homeostasis. In an obesity
state, it participates in the induction of chronic systemic inflammation
accompanied by pro-inflammatory cytokines and fatty acid elevation. For this
reasons, adipose tissue is involved in, e.g., insulin resistance, type 2 diabetes
or hyperlipidemia development. In our previous study, we have shown that
riboflavin deficiency induces a pathological pro-inflammatory response of
macrophages, the main component of adipose tissue. Therefore, in the current
study, we investigated the alteration of the pro-inflammatory activity of
adipocytes. MAIN METHODS: The study was conducted on mouse 3T3 L1 preadipocytes
differentiated to adipocyte and culture in the state of riboflavin deficiency
(3.1nM) or control condition (10.4nM). The cell viability, adiposity and glucose
uptake was assessed. Moreover, mRNA expression, as well as crucial pro
inflammatory cytokines (TNFalpha, IL-6) and adipokines (adiponectin, leptin,
resistin) release and NFkappaB activation, were evaluated. KEY FINDINGS: Results
showed that riboflavin deprivation induced a significant elevation in adipocyte
lipolysis and enhance obesity-related apoptosis of adipocytes. The generation of
reactive oxygen species was enhanced in riboflavin-deficient adipocytes by 43%.
Moreover, NFkappaB phosphorylation and the expression and release of both
TNFalpha, IL-6 as well as leptin were elevated in a deficient group what was
accompanied by a reduction of adiponectin level. CONCLUSION: Our study shows that
riboflavin deficiency can promote the intensification of pro-inflammatory
activity of adipocyte cells, leading consequently to the severity of chronic
inflammation that accompanies obesity state.
PMID- 28414073
TI - Metabolic and affective consequences of fatherhood in male California mice.
AB - Physiological and affective condition can be modulated by the social environment
and parental state in mammals. However, in species in which males assist with
rearing offspring, the metabolic and affective effects of pair bonding and
fatherhood on males have rarely been explored. In this study we tested the
hypothesis that fathers, like mothers, experience energetic costs as well as
behavioral and affective changes (e.g., depression, anxiety) associated with
parenthood. We tested this hypothesis in the monogamous, biparental California
mouse (Peromyscus californicus). Food intake, blood glucose and lipid levels,
blood insulin and leptin levels, body composition, pain sensitivity, and
depression-like behavior were compared in males from three reproductive groups:
virgin males (VM, housed with another male), non-breeding males (NB, housed with
a tubally ligated female), and breeding males (BM, housed with a female and their
first litter). We found statistically significant (P<0.007, when modified for
Adaptive False Discovery Rate) or nominally significant (0.00790% of B. fragilis, non-fragilis Bacteroides and Parabacteroides
isolates. With the exception of B. fragilis division II, imipenem was active
against 88.0%-98.3% of isolates of the other species. Susceptibility rates for
clindamycin (14.4%-54.3%) and moxifloxacin (33.3%-80.6%) were low across all
species and many isolates had no inhibition zone around the discs. E-test testing
confirmed 8.2% (61/741) and 1.6% (12/741) isolates as nonsusceptible to imipenem
and metronidazole, respectively with B. fragilis and B. thetaoiotaomicron
accounting for a large share of the observed resistance to both agents. Two
imipenem-resistant and one metronidazole-resistant B. dorei were misidentified as
B. vulgatus by MALDI-TOF MS. These data highlights the importance anaerobic
susceptibility testing in clinical laboratories to guide therapy.
PMID- 28414108
TI - Improvingthecatalytic properties and stability of immobilized gamma
glutamyltranspeptidase by post-immobilization with PharmalyteMT 8-10.5.
AB - gamma-Glutamyltranspeptidase (GGT) is a dimeric protein that specifically
catalyzes the transfer of gamma-glutamyl in the optimum pH range of 8.5-9.0, but
has poor in vitro stability under the alkaline conditions. In the present work,
GGT was immobilized on a mesoporoustitania oxide whisker (MTWs) carrier to afford
MTWs-GGT that was further modified with PharmalyteMT (Phar) 8.0-10.5 to yield
MTWs-GGT-Phar. Phar absorbed on MTWs-GGT to form a buffering layer with an
isoelectric point of ~9.2 that isolated the immobilized enzyme from the liquid
bulk and significantly in proved the pH tolerance and stability of the
immobilized GGT. The MTWs-GGT-Phar exhibited a stable enzyme activity in the pH
range of 6.0-11.0 and an optimum temperature 10 degrees C higher than GGT. Its pH
stability at pH 11.0 and thermal stability at 50 degrees C were respectively 23.7
times and 19.4 times higher than those of GGT. In addition, the affinity constant
of MTWs-GGT-Phar towards GpNA (Km) was 0.597mM, slightly lower than that of free
GGT, indicating that Phar had a protective effect on the structure of GGT.
PMID- 28414109
TI - Synthesis and characterization of chitosan nanoparticles and their effect on
Fusarium head blight and oxidative activity in wheat.
AB - The main aim of present study was to prepare chitosan (CS) and chitosan
nanoparticles (CS/NPs) to evaluate their antifungal and oxidative activity.
CS/NPs were prepared based on the ionic gelation of CS with tripolyphosphate
(TPP) anions by using centrifugation and pH change. The obtained nanoparticles
(NPs) were characterized by size and zeta potential analysis. The antifungal
activity of the CS and CS/NPs were evaluated on the Fusarium graminearum, which
causes Fusarium head blight (FHB) on wheat by the method of spraying on the
Potato dextrose agar (PDA) medium. The Dynamic light scattering (DLS) indicated
that particle diameter (z-average) was approximately 180.9+/-35.5-339.4+/-50.9
and 225.7+/-42.81-595.7+/-81.7nm for NPs prepared from CS with different
molecular weights by using centrifugation and pH change methods, respectively.
Different concentrations of CS and NPs were tested to know the inhibitory effect
of F. graminearum. Low molecular weight (LMW) CS and its NPs had high potential
of antifungal activity on suppress of fungus growth. The maximum percentage of
growth reduction was 68.18%, and 77.5% by CS and its NPs at concentrations of
1000 and 5000ppm, respectively. In greenhouse trials, at 28days after inoculation
(dpi), the area under the disease progress curve (AUDPC) from 7 dpi to 28 dpi of
control plants treated with acetic acid aqueous solution and distilled water was
almost up to 7.36 and 7.7, respectively, while plants treated with CS and NPs
only had approximately 3.61 and 3.34, respectively. Results revealed that H2O2
accumulations displayed a different pattern during the activation of plant
defense systems, it had brownish sites on the infected palea. Since 24h post
inoculation (hpi), the H2O2 accumulations were shown in both CS and NPs, and the
elevated H2O2 accumulation appeared in 72 hpi in both treatments. CS and NPs at
high concentration increased the degree of tissue and cell injury. The obtained
results clearly suggest that CS and its NPs have remarkable potential for further
field screening towards crop protection.
PMID- 28414110
TI - Rifampicin as a novel tyrosinase inhibitor: Inhibitory activity and mechanism.
AB - In this study, the inhibitory effect and mechanism of rifampicin on the activity
of tyrosinase were investigated for developing a novel tyrosinase inhibitor. It
was found to have a significant inhibition on the activity of tyrosinase
(IC50=90+/-0.6MUM). From the kinetics analysis, it was proved to be a reversible
and noncompetitive type inhibitor of the enzyme with the KI value of 94+/-3.5MUM.
The results obtained from intrinsic fluorescence quenching indicated that
rifampicin could interact with tyrosinase. In particular, the drastic decrease of
fluorescence intensity was due to the formation of a rifampicin-enzyme complex in
a static procedure which was mainly driven by hydrophobic forces and hydrogen
bonding. Moreover, the ANS-binding fluorescence analysis suggested that
rifampicin binding to tyrosinase changed the polarity of the hydrophobic regions.
Molecular docking analysis further revealed that the hydrogen bonds were
generated between rifampicin and amino residues Leu7, Ser52, and Glu107 in the B
chain of the enzyme. And the hydrophobic forces produced through the interaction
of rifampicin with B chain residues Pro9, Pro14, and Trp106. This work identified
a novel tyrosinase inhibitor and potentially contributed to the usage of
rifampicin as a potential hyperpigmentation drug.
PMID- 28414111
TI - Screening for the best detergent for the isolation of placental membrane
proteins.
AB - Although membrane proteins (MPs) play crucial roles in physiological processes,
information on them are insufficient, mostly due to their peculiar nature and
surrounding which demand specific procedures for their extraction (using
detergents) and analysis. A pallet of ten detergents and beta-cyclodextrin was
employed to investigate their efficiency in extracting total placental MPs,
glycoproteins and insulin-like growth factor receptors (IR/IGF1R/IGF2R).
Regardless of detergent used, the identity of major extracted proteins was the
same. Glycoproteins extracted with Triton X-100 contained the greatest variety
and quantity of glycans recognised by fifteen lectins, pointing to this detergent
as universal medium for the extraction of membrane glycoproteins. Glycoproteins
extracted using Brij 35 exhibited weak interaction with only seven lectins and
were differently recognised by lectins of the similar glycan specificity. Brij
35, Tween 20, saponin and digitonin selectively extracted IGF2R compared to other
two receptors. Pilot experiments should be conducted in order to choose adequate
detergent for the extraction of specific MP. To obtain preparations enriched in
specific receptor of the insulin/IGF system sequential solubilisation of
placental MPs can be proposed: to use Brij 35 to extract IGF2R and subject the
insoluble remaining suspension to Triton X-114 in order to extract most of IGF1R
with small amounts of IR.
PMID- 28414112
TI - Binding of erucic acid with human serum albumin using a spectroscopic and
molecular docking study.
AB - Erucic acid (EA) is one of the key fatty acids usually found in canola oil,
mustard oil and rapeseed oil. Consumption of EA in primates was found to cause
myocardial lipidosis and cardiac steatosis. To have an insight of the effect of
EA in humans, we performed in vitro interaction studies of EA with the primary
plasma protein, human serum albumin (HSA). Spectroscopic (UV-vis and
fluorescence) analysis of the HSA-EA interaction revealed a static mode of
quenching with binding constant Kb ~104 reflecting high affinity of EA for HSA.
The negative value of DeltaG degrees for binding of EA to HSA in the
fluorescence studies indicates the process to be spontaneous. Thermodynamic
signatures of the HSA-EA interaction in the complex reflect dominance of hydrogen
bonds. Despite predominance of hydrogen bonds, hydrophobic interactions in the
HSA-EA complex were found acting as a contributing factor in the binding of EA to
HSA, observed as structural change in the far-UV CD spectra. Forster's resonance
energy transfer of the EA-HSA complex revealed a distance of 3.2nm between
acceptor molecules (EA) and the donor Trp residue of HSA. To have a deeper
insight of the structural dependence of the HSA-EA interaction in the complex,
thermodynamic study was supplemented with molecular docking. The molecular
docking analysis further highlighted the EA binding in the subdomain IIIA (Sudlow
site II) of HSA. The information generated in the study reflects greater
pharmacological significance of EA and highlights its importance in the clinical
medicine.
PMID- 28414113
TI - sept8a and sept8b mRNA expression in the developing and adult zebrafish.
AB - Septins are highly conserved GTP-binding proteins involved in numerous cellular
processes. Despite a growing awareness of their roles in the cell biology,
development and signal transmission in nervous systems, comparably little is
known about precise septin expression. Here, we use the well-established model
organism zebrafish (Danio rerio) to unravel the expression of sept8a and sept8b,
with special focus on the CNS. We performed whole mount RNA in situ hybridization
on zebrafish 1-4 dpf in combination with serial sectioning of epon-embedded
samples as well as on brain sections of adult zebrafish to obtain precise
histological mapping of gene expression. Our results show a common expression of
both genes at embryonic stages, whereas sept8a is mainly restricted to the gill
arches and sept8b to specific brain structures at later stages. Brains of adult
zebrafish reveal a large spatial overlap of sept8a and sept8b expression with few
regions uniquely expressing sept8a or sept8b. Our results indicate a neuronal
expression of both genes, and additionally suggest expression of sept8b in glial
cells. Altogether, this study provides a first detailed insight into the
expression of sept8a and sept8b in zebrafish and contributes to a more
comprehensive understanding of septin biology in vertebrate model systems.
PMID- 28414114
TI - Why Do Long-Distance Travelers Have Improved Pancreatectomy Outcomes?
AB - BACKGROUND: Centralization of complex surgical care has led patients to travel
longer distances. Emerging evidence suggested a negative association between
increased travel distance and mortality after pancreatectomy. However, the reason
for this association remains largely unknown. We sought to unravel the
relationships among travel distance, receiving pancreatectomy at high-volume
hospitals, delayed surgery, and operative outcomes. STUDY DESIGN: We identified
44,476 patients who underwent pancreatectomy for neoplasms between 2004 and 2013
at the reporting facility from the National Cancer Database. Multivariable
analyses were performed to examine the independent relationships between
increments in travel distance mortality (30-day and long-term survival) after
adjusting for patient demographics, comorbidity, cancer stage, and time trend. We
then examined how additional adjustment of procedure volume affected this
relationship overall and among rural patients. RESULTS: Median travel distance to
undergo pancreatectomy increased from 16.5 to 18.7 miles (p for trend < 0.001).
Although longer travel distance was associated with delayed pancreatectomy, it
was also related to higher odds of receiving pancreatectomy at a high-volume
hospital and lower postoperative mortality. In multivariable analysis, difference
in mortality among patients with varying travel distance was attenuated by
adjustment for procedure volume. However, longest travel distance was still
associated with a 77% lower 30-day mortality rate than shortest travel among
rural patients, even when accounting for procedure volume. CONCLUSIONS: Our large
national study found that the beneficial effect of longer travel distance on
mortality after pancreatectomy is mainly attributable to increase in procedure
volume. However, it can have additional benefits on rural patients that are not
explained by volume. Distance can represent a surrogate for rural populations.
PMID- 28414115
TI - Cost Analysis of a Surgical Consensus Guideline in Breast-Conserving Surgery.
AB - BACKGROUND: The Society of Surgical Oncology and American Society of Radiation
Oncology consensus statement was the first professional guideline in breast
oncology to declare "no ink on tumor" as a negative margin in patients with
stages I/II breast cancer undergoing breast-conservation therapy. We sought to
analyze the financial impact of this guideline at our institution using a
historic cohort. STUDY DESIGN: We identified women undergoing re-excision after
breast-conserving surgery for invasive breast cancer from 2010 through 2013 using
a prospectively maintained institutional database. Clinical and billing data were
extracted from the medical record and from administrative resources using CPT
codes. Descriptive statistics were used in data analysis. RESULTS: Of 254 women
in the study population, 238 (93.7%) had stage I/II disease and 182 (71.7%) had
invasive disease with ductal carcinoma in situ. A subcohort of 83 patients
(32.7%) who underwent breast-conservation therapy for stage I/II disease without
neoadjuvant chemotherapy had negative margins after the index procedure, per the
Society of Surgical Oncology and American Society of Radiation Oncology
guideline. The majority had invasive ductal carcinoma (n = 70 [84.3%]) and had
invasive disease (n = 45 [54.2%]), and/or ductal carcinoma in situ (n = 49
[59.0%]) within 1 mm of the specimen margin. Seventy-nine patients underwent 1 re
excision and 4 patients underwent 2 re-excisions, accounting for 81 hours of
operative time. Considering facility fees and primary surgeon billing alone, the
overall estimated cost reduction would have been $195,919, or $2,360 per affected
patient, under the guideline recommendations. CONCLUSIONS: Implementation of the
Society of Surgical Oncology and American Society of Radiation Oncology consensus
guideline holds great potential to optimize resource use. Application of the
guideline to a retrospective cohort at our institution would have decreased the
overall re-excision rate by 5.6% and reduced costs by nearly $200,000. Additional
analysis of patient outcomes and margin assessment methods is needed to define
the long-term impact on surgical practice.
PMID- 28414117
TI - Global Surgery: Lifeline for the US Military Surgeon.
PMID- 28414116
TI - The Largest European Single-Center Experience: 300 Laparoscopic Pancreatic
Resections.
AB - BACKGROUND: Although laparoscopic pancreatic resection (LPR) has become routine,
large single-center series are still lacking. Our aim was to analyze the results
of a large European single-center series of LPR. STUDY DESIGN: Between January
2008 and September 2015, 300 LPRs were performed and studied prospectively,
including 165 (55%) distal pancreatectomies, 68 (23%) pancreaticoduodenectomies
(PDs), 30 (10%) enucleations, 35 (11%) central pancreatectomies, and 2 (1%) total
pancreatectomies. RESULTS: Mean age was 54 +/- 15.4 years old (range 17 to 87
years), and most patients were women (58%). Laparoscopic pancreatic resection was
performed for malignancy (46%), low potential malignant (44%), or benign (10%)
diseases. The mean operative durations were 211 +/- 102 minutes (range 30 to 540
minutes) for the entire population and 351 +/- 59 minutes (range 240 to 540
minutes) for PD, and decreased with the learning curve. Mean blood loss was 229
+/- 269 mL (range 0 to 1,500 mL), and 13 patients (4%) received transfusions.
Conversion to an open procedure was required in 12 patients (4%), and only 5 in
the last 250 patients (14% vs 2%; p < 0.001). Mortality occurred in 4 (1.3%)
patients and only after PD (5.8%). Common complications were pancreatic fistula
(n = 124, 41%), bleeding (n = 35, 12%), and reoperation (n = 28, 9%). The
postoperative outcomes were less favorable in procedures with a reconstruction
phase (n = 105) than in those without (n = 195), with increased mortality (3.8%
vs 0%; p = 0.04), overall morbidity (76% vs % 52%; p < 0.001), and mean hospital
stay (26 +/- 15 days vs 16 +/- 10 days; p < 0.001). CONCLUSIONS: Laparoscopic
pancreatic resection without a reconstruction phase has excellent outcomes; LPR
with a reconstruction phase, especially PD, has less favorable outcomes, and
further randomized studies are required to draw conclusions on the safety and
benefits of this approach.
PMID- 28414118
TI - Comparing existing classifications of fistula-in-ano in 440 operated patients: Is
it time for a new classification? A Retrospective Cohort Study.
AB - BACKGROUND: Fistula-in-ano are classified so as to grade them according to
increasing complexity which can help guide their management. The classifications
used are Parks, St James Hospital University (SJHU) and Standard Practice Task
Force (SPTF). Laying open (fistulotomy) of the fistula tract is the most commonly
done procedure for fistula-in-ano and has high success rate. The lower grade
fistulas are supposed to have low risk of incontinence when laid open and vice
versa. The objective of the study was to evaluate the efficacy of the existing
classifications. MATERIALS & METHODS: 440 consecutive fistula-in-ano patients
operated over four years were analyzed on the basis of preoperative MRI scan and
operative findings. It was assessed whether the amenability to fistulotomy
(measurement of fistula simplicity) correlated with the fistula-in-ano grades in
different classifications. RESULTS: Out of 440 patients operated, 242 underwent
fistulotomy whereas 198 underwent sphincter-sparing procedures for complex
fistula. As per SJHU classification, the amenability to fistulotomy was 99.1% in
Grade-I, 82.1% in Grade-II, 46.2% in Grade-III, 29.0% in Grade-IV and 5.4% in
Grade-V. In Park's classification, the amenability to fistulotomy was 93.5% in
Grade-I, 34.8% in Grade-II, 5.4% in Grade-III and 0% in Grade-IV. As per SPTF
classification, 99.3% of simple and 32.1% of complex fistulas underwent
fistulotomy. Even the higher grade fistula-in-ano in all three classifications
had high rate of amenability to fistulotomy. Therefore none of the above
classifications were accurate. A new classification is being proposed which
divides fistula-in-ano in 5 grades in order of increasing complexity. Grade I &
II are simple fistulas (fistulotomy be done conveniently) and Grade III-V are
high complex fistulas (fistulotomy should not be attempted). The data was
analyzed as per new classification and found it to be highly accurate.
CONCLUSIONS: None of the existing classifications accurately correlated between
the grade and the complexity of fistula. A new classification is being proposed.
PMID- 28414119
TI - Efficacy of the fissureless technique on decreasing the incidence of prolonged
air leak after pulmonary lobectomy: A systematic review and meta-analysis.
AB - OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of
fissureless technique in pulmonary lobectomy by applying a meta-analysis of the
current evidence. METHODS: We searched the PubMed, EMBASE and the Web of Science
databases to recognize the eligible articles. The relative risk (RR) and weighted
mean difference (WMD) with the corresponding 95% confidence interval (CI) served
as the summarized estimates for dichotomous variables and continuous variables,
respectively. Sensitivity analysis and publication bias tests were also performed
to perceive potential bias risks. RESULTS: There were 6 studies with 843 surgical
patients included into this meta-analysis. Finally, the meta-analysis
demonstrated that fissureless technique could significantly reduce the incidence
of prolonged air leak (PAL)[RR = 0.40; 95%CI=(0.24, 0.68); P = 0.001], the length
of hospital stay [WMD = -0.52; 95%CI=(-0.87, -0.18); P = 0.003] and the duration
of chest tube [WMD = -0.44; 95%CI=(-0.74, -0.14); P = 0.004]. Fissureless
technique had also showed the benefit on decreasing the complication rate after
lobectomy but without a statistical significance [RR = 0.77; 95%CI=(0.55, 1.07);
P = 0.119]. In addition, no difference was observed in the operation time between
the fissureless lobectomy and conventional lobectomy [WMD = 5.32; 95%CI=(-3.18,
13.83); P = 0.220]. CONCLUSIONS: Fissureless lobectomy is a superior alternative
to conventional lobectomy in terms of preventing the PAL and shortening the
length of hospital stay and chest tube duration. More multi-institution
randomized controlled trials are required to confirm the validity of our findings
in the future.
PMID- 28414120
TI - The predictive value of integrated inflammation scores in the survival of
patients with resected hepatocellular carcinoma: A Retrospective Cohort Study.
AB - BACKGROUND: Evidence supports the predictive potential of inflammatory marker
derived scores (inflammation scores) and hepatitis B virus (HBV) infection on
prognosis of patients with hepatocellular carcinoma (HCC). However, no study has
longitudinally assessed the predictive values of inflammation scores combined
with hepatitis B virus status on survival of these patients. Therefore, a study
was designed to evaluate the prognostic capacity of preoperative, dynamic changes
in integrated scores, through a combination of general inflammation scores and
HBV infection status, on HCC patients undergoing tumor resection. METHODS: The
clinicopathological data of 247 patients with primary HCC who underwent liver
resection were collected. Inflammation-related laboratory examinations were
performed 1 week before operation, and 1 week, 1 month, 3months, and 6months
after operation. The prognostic values of preoperative and dynamic changes in
integrated inflammation scores were studied using the Cox regression models.
RESULTS: Elevated preoperative integrated inflammation scores, including co
Glasgow prognostic score (coGPS), co-modified Glasgow prognostic score (comGPS),
co-C reactive protein to albumin ratio (coCRP/ALB), co-prognostic index (coPI),
co-neutrophil to lymphocyte ratio (coNLR), co-lymphocyte to monocyte ratio
(coLMR), coNLR-PLR and coCRP/ALB-PLR, were associated with decreased overall
survival (OS). Dynamic changes in coGPS, comGPS, coCRP/ALB, coPI, coPLR, coNLR,
coSII, coNLR-PLR, and coCRP/ALB-PLR were independent prognostic factors of OS.
coCRP/ALB-PLR was significantly associated with disease free survival.
CONCLUSIONS: Preoperative and dynamic changes in integrated inflammation scores,
particularly for coCRP/ALB-PLR were important and stable prognostic markers in
HCC.
PMID- 28414121
TI - Neural-derived estradiol regulates brain plasticity.
AB - In addition to be an ovarian hormone, estradiol is a neurosteroid synthesized by
neural cells. The brain is a steroidogenic tissue that metabolizes testosterone
to estradiol. The last step in the synthesis of estradiol is catalyzed by the
enzyme aromatase, which is widely expressed in the brain of male and female
animals and humans. Studies that have manipulated the expression or the activity
of aromatase have revealed that brain-derived estradiol acts as a neuromodulator
and regulates different forms of brain plasticity in male and female animals. The
regulation of neuroplastic events by brain-derived estradiol probably
participates in the effects of brain aromatase on behavior and cognition.
PMID- 28414122
TI - RIFM fragrance ingredient safety assessment, isononyl propionate, CAS Registry
Number 65155-45-5.
PMID- 28414123
TI - Anti-factor Xa activities of zingerone with anti-platelet aggregation activity.
AB - Zingerone (ZGR), a phenolic alkanone found in Zingiber officinale, has been
reported to have various pharmacological activities such as anti-inflammatory,
anti-apoptotic, and protecting myocardial infarction and irritable bowel
disorder. The aim was to identify the unreported bioactive anti-factor Xa (FXa)
and anti-platelet activities of ZGR. ZGR was evaluated for their anti-FXa and
anti-platelet aggregation properties by monitoring clotting time, platelet
aggregation, FXa activity and production, and thrombus formation. ZGR reduced
activated partial thromboplastin time and it inhibited the catalytic activity of
FXa toward its substrate S-2222 in a noncompetitive inhibition model and
inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619
(not thrombin). However, ZGR did not prolong bleeding time in mice, as shown by
tail clipping. ZGR also inhibited ADP- and U46619- induced phosphorylation of
myristolated alanine-rich C-kinase substrate (MARCKS) and the expressions of P
selectin and PAC-1 in platelets. In an animal model of arterial and pulmonary
thrombosis, ZGR showed enhanced antithrombotic effects. ZGR also elicited
anticoagulant effects in mice. Our results reveal that ZGR is an antithrombotic
compound with both FXa inhibitory and anti-platelet aggregation activities.
Collectively, these results show that ZGR could serve as candidates and provide
scaffolds for the development of new anti-FXa and anti-platelet drugs.
PMID- 28414124
TI - Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive
toxicity in testis on male offspring.
AB - In the present study, we evaluated the toxic effects on the testis of the male
offspring of MC-LR exposure during fetal and lactational periods. Pregnant
females were distributed into two experimental groups: control group and MC-LR
group which were exposed to 0 and 10 MUg/L of MC-LR, respectively, through
drinking water separately during fetal and lactational periods. At the age of 30
days after birth, the male offspring were euthanized. The body weight, testis
index, and histomorphology change were observed and the global changes of piwi
interacting RNA (piRNA) expression were evaluated. The results revealed that MC
LR was found in the testis of male offspring, body weight and testis index
decreased significantly, and testicular tissue structure was damaged in the MC-LR
group. In addition, the exposure to MC-LR resulted in an altered piRNA expression
profile and an increase of the cell apoptosis and a decrease of the cell
proliferation in the testis of the male offspring. It was reasonable to speculate
that the toxic effects on reproductive system of the male offspring in MC-LR
group might be mediated by piRNAs through the regulation of the target genes. As
far as we are aware, this is the first report showing that MC-LR could play a
role in disorder of proliferative and cell apoptosis in the testis of the male
offspring by the maternal transmission effect of toxicity.
PMID- 28414125
TI - The number of the C-terminal transmembrane domains has the potency to specify
subcellular localization of Sec22c.
AB - Sec22c has been characterized as an endoplasmic reticulum (ER)-localized
transmembrane protein involved in regulation of the vesicle transport between the
ER and the Golgi. Sec22c has several isoforms generated by alternative splicing
that changes the number of the C-terminal transmembrane domains (TMDs). However,
the physiological significance of the splicing remains unknown. Here we show that
the splicing isoforms containing four TMDs unexpectedly localized at cis-Golgi,
whereas the splicing isoforms containing less than four TMDs localized at the ER.
The C-terminal fragment containing the four TMDs was sufficient for the cis-Golgi
localization and bound to ADP-ribosylation factor 4 (ARF4). ARF4 knockdown and
overexpression of a constitutively active mutant of ARF4 decreased the cis-Golgi
localization of the C-terminal fragment and the full-length protein,
respectively. These results indicate that the splicing-dependent changes in the
number of TMDs allow Sec22c to regulate the subcellular localization in
cooperation with ARF4, implying that Sec22c will function at the Golgi as well as
the ER.
PMID- 28414126
TI - Characterization of the novel protein KIAA0564 (Von Willebrand Domain-containing
Protein 8).
AB - The VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564.
Based on the observation, by similarity, that the protein encoded by KIAA0564
contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand
Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost
unknown. The purpose of this study was to characterize the tissue distribution,
cellular location, and function of VWA8. In mice VWA8 protein was mostly
distributed in liver, kidney, heart, pancreas and skeletal muscle, and is present
as a long isoform and a shorter splice variant (VWA8a and VWA8b). VWA8 protein
and mRNA were elevated in mouse liver in response to high fat feeding. Sequence
analysis suggests that VWA8 has a mitochondrial targeting sequence and domains
responsible for ATPase activity. VWA8 protein was targeted exclusively to
mitochondria in mouse AML12 liver cells, and this was prevented by deletion of
the targeting sequence. Moreover, the VWA8 short isoform overexpressed in insect
cells using a baculovirus construct had in vitro ATPase activity. Deletion of the
Walker A motif or Walker B motif in VWA8 mostly blocked ATPase activity,
suggesting Walker A motif or Walker B motif are essential to the ATPase activity
of VWA8. Finally, homology modeling suggested that VWA8 may have a structure most
confidently similar to dynein motor proteins.
PMID- 28414127
TI - Crystal structure of the flagellar chaperone FliS from Bacillus cereus and an
invariant proline critical for FliS dimerization and flagellin recognition.
AB - FliS is a cytoplasmic flagellar chaperone for the flagellin, which polymerizes
into filaments outside of the flagellated bacteria. Cytoplasmic interaction
between FliS and flagellin is critical to retain the flagellin protein in a
monomeric form, which is transported from the cytoplasm through the flagellar
export apparatus to the extracellular space for filament assembly. Defects in the
FliS protein directly diminish bacterial motility, pathogenicity, and viability.
Although the overall structure of FliS is known, structural and mutational
studies on FliS from other bacterial species are still required to reveal any
unresolved biophysical features of FliS itself or functionally critical residues
for flagellin recognition. Here, we present the crystal structure of FliS from
Bacillus cereus (BcFliS) at 2.0 A resolution. FliS possesses a highly dynamic N
terminal region, which is appended to the common four-helix bundle structure. An
invariant proline residue (Pro17 in B. cereus FliS) was identified in all known
FliS sequences between the N-terminal region and the four-helix bundle. The N
terminal proline residue functions as a helix breaker critical for FliS
dimerization and flagellin recognition.
PMID- 28414128
TI - Impaired degradation of medullary WNK4 in the kidneys of KLHL2 knockout mice.
AB - Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and
Cullin3 (CUL3) genes were identified as being responsible for hereditary
hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the
KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of
interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired
ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC
cascade in the kidney's distal convoluted tubules (DCT). KLHL2, which is highly
homologous to KLHL3, was reported to ubiquitinate and degrade WNKs in vitro.
Mutations in KLHL2 have not been reported in patients with PHAII, suggesting that
KLHL2 plays a different physiological role than that played by KLHL3 in the
kidney. To investigate the physiological roles of KLHL2 in the kidney, we
generated KLHL2-/- mice. KLHL2-/- mice did not exhibit increased phosphorylation
of the OSR1/SPAK-NCC cascade and PHAII-like phenotype. KLHL2 was predominantly
expressed in the medulla compared with the cortex. Accordingly, medullary WNK4
protein levels were significantly increased in the kidneys of KLHL2-/- mice.
KLHL2 is indeed a physiological regulator of WNK4 in vivo; however, its function
might be different from that of KLHL3 because KLHL2 mainly localized in medulla.
PMID- 28414129
TI - The Arabidopsis endoplasmic reticulum associated degradation pathways are
involved in the regulation of heat stress response.
AB - The Cytosolic Protein Response (CPR) in the cytosol and the Unfolded Protein
Response (UPR) and ER-associated degradation (ERAD) in the endoplasmic reticulum
are major pathways of the cellular proteostasis network. However, despite years
of effort, how these protein quality control systems coordinated in vivo remains
largely unknown, particularly in plants. In this study, the roles of two
evolutionarily conserved ERAD pathways (DOA10 and HRD1) in heat stress response
were investigated through reverse genetic approaches in Arabidopsis. Phenotypic
analysis of the mutants showed that the two ERAD pathways additively play
negative roles in heat tolerance, which was demonstrated by higher survival rate
and lower electrolyte leakage in the loss of function mutants compared to the
wild type plants. Importantly, gene expression analysis revealed that the mutant
plants showed elevated transcriptional regulation of several downstream genes,
including those encoding CPR and UPR marker genes, under both basal and heat
stress conditions. Finally, multiple components of ERAD genes exhibited rapid
response to increasing temperature. Taken together, our data not only unravels
key insights into the crosstalk between different protein quality control
processes, but also provides candidate genes to genetically improve plant heat
tolerance in the future.
PMID- 28414130
TI - Effect of oxidation of the non-catalytic beta-propeller domain on the substrate
specificity of prolyl oligopeptidase from Pleurotus eryngii.
AB - Enzymes belonging to the S9 family of prolyl oligopeptidases are of interest
because of their pharmacological importance and have a non-catalytic beta
propeller domain. In this study, we found that the oxidation of Met203, which
lies on surface of the beta-propeller domain, leads to change in the substrate
specificity of eryngase, an enzyme from Pleurotus eryngii and a member of the S9
family of prolyl oligopeptidases. The activity of eryngase for L-Phe-p
nitroanilide was maintained following hydrogen peroxide treatment but was
dramatically reduced for other p-nitroanilide substrates. MALDI-TOF MS analysis
using tryptic peptides of eryngase indicated that the change in substrate
specificity was triggered by oxidizing Met203 to methionine sulfoxide. In
addition, mutations of Met203 to smaller residues provided specificities similar
to those observed following oxidation of the wild-type enzyme. Substitution of
Met203 with Phe significantly decreased activity, indicating that Met203 may be
involved in substrate gating.
PMID- 28414131
TI - Cyclical corticosterone administration sensitizes depression-like behavior in
rats.
AB - Because stress is a significant risk factor for depression, many animal models of
depression employ chronic stress as a precipitating event. However, almost
without exception, stress-induced animal models of depression focus on a single
bout of depression and therefore, they do not provide any means to understand the
typical cycling of mood observed in most patients with depression. Here we
assessed whether repeated cycles of exposure to the stress hormone corticosterone
would sensitize depression-like behavior. Rats were treated with corticosterone
(CORT; 20 or 40mg/kg) or vehicle for two cycles (21days each), followed by a 21
day recovery period. Depression-like behavior was assessed via repeated forced
swim tests (FSTs) in the middle and at the end of each CORT treatment and at the
end of each recovery period. Our results showed that CORT administration for two
cycles produces increasingly greater effects on depression-like behavior and a
decrease in recovery between cycles. Potential confounding effects of body weight
and repetitive behavioral testing are considered in the interpretation of these
effects. Our approach of using more than one cycle of CORT exposure provides
strong face validity as it mimics several aspects of human depression. The use of
multiple cycles of CORT exposure may provide a means to study the episode
recurrence seen in more than 70% of patients with depression.
PMID- 28414132
TI - Epigenetic modification of glucocorticoid receptor promoter I7 in maternally
separated and restraint-stressed rats.
AB - Glucocorticoid receptor (GR) promoter I7 is susceptible to epigenetic changes
induced by environmental influences. Early life stress (ELS) has a persistent
impact on GR expression, as well as behavior, in adult rodents via epigenetic
changes of GR promoter I7. Moreover, various stressors can induce histone
modifications in this region during adulthood. Thus, the present study aimed to
investigate whether maternally separated (MS) rats exposed to chronic restraint
stress (RS) would exhibit histone modifications of GR promoter I7 in the
hippocampus. Rats were subjected to MS (3h per day) on postnatal days (PND) 1-21.
Then, during adulthood (PND 56-77), the rats were exposed to RS (2h per day)
followed by treatment with escitalopram (10mg/kg). The MS and RS groups exhibited
significant decreases in total and exon I7 GR mRNA levels and the combination of
MS and RS exerted a greater effect on these mRNA levels than either MS or RS
alone. Additionally, both the MS and RS groups showed significant reductions in
histone H3 acetylation at GR promoter I7 and the combination of MS and RS had a
greater effect than did either MS or RS alone. Chronic escitalopram treatment
ameliorated these changes. The present results indicate that postnatal MS and
adult RS influence GR expression through histone modification at GR promoter I7,
and that the combination of the two stressors potentiates these changes.
Furthermore, epigenetic mechanisms are involved in escitalopram action.
PMID- 28414133
TI - Complexity of weighted graph: A new technique to investigate structural
complexity of brain activities with applications to aging and autism.
AB - In recent years complexity of the brain structure in healthy and disordered
subjects has been studied increasingly. But to the best of the authors'
knowledge, researchers so far have investigated the structural complexity only in
the context of two restricted networks known as Small-World and Scale-free
networks; whereas other aspects of the structural complexity of brain activities
may be affected by aging and neurodegenerative disorders such as the Alzheimer's
disease and autism spectrum disorder. In this study, two general complexity
metrics of graphs, Graph Index Complexity and Offdiagonal Complexity are proposed
as general measures of complexity, not restricted to SWN only. They are adopted
to measure the structural complexity of the weighted graphs instead of the common
binary graphs. Fuzzy Synchronization Likelihood is applied to the EEGs and their
sub-bands, as a functional connectivity metric of the brain, to construct the
functional connectivity graphs. Two applications are used to evaluate the
efficacy of the complexity measures: diagnosis of autism and aging, both based on
EEG. It was discovered that the Graph Index Complexity of gamma band is
discriminative in distinguishing autistic children from non-autistic children.
Also, Offdiagonal Complexity of theta band in young subjects was observed to be
significantly different than old subjects. This study shows that changes in the
structure of functional connectivity of brain in disorders and different healthy
states can be revealed by unrestricted metrics of graph complexity. While the
applications presented in this paper are based on EEG, the approach is general
and can be used with other modalities such as fMRI, MEG, etc. Further, it can be
used to study every other neurological and psychiatric disorder.
PMID- 28414134
TI - Targeted intracorneal delivery-Biodistribution of triamcinolone acetonide
following topical iontophoresis of cationic amino acid ester prodrugs.
AB - The aim was to investigate intracorneal iontophoresis of biolabile triamcinolone
acetonide (TA) amino acid ester prodrugs (TA-AA). Arginine and lysine esters of
TA (TA-Arg and TA-Lys, respectively) were synthesized and characterized;
quantification was performed by HPLC-UV and UHPLC-MS/MS. The aqueous solubility
of the prodrugs (at pH 5.5) was ~1000-fold greater than TA. Anodal iontophoresis
(10min at 3mA/cm2) of TA-AA was investigated using isolated porcine cornea.
Although no statistically significant difference was observed in total
intracorneal delivery of TA (468.25+/-59.70 and 540.85+/-79.16nmolTA/cm2, for TA
Arg and TA-Lys, respectively), the different susceptibilities of the prodrugs to
hydrolysis influenced intracorneal biodistribution. Quantification of TA in
twenty-five 40MUm thick corneal lamellae revealed significantly deeper
penetration of TA following TA-Lys iontophoresis. Its superior resistance to
hydrolysis enabled sustained electromigration into the deeper cornea suggesting
judicious prodrug selection might enable targeted regioselective drug delivery.
The intracorneal biodistribution following anodal iontophoresis of TA-Arg (2.3mM;
10min, 3mA/cm2) was visualized by full field optical coherence tomography
providing qualitative confirmation of the extensive intracorneal penetration of
TA. Short duration iontophoresis of TA-AA prodrugs may improve deep corneal
bioavailability and efficacy in vivo, constituting a "single-shot" treatment
option for corneal allograft rejection.
PMID- 28414135
TI - Gastrointestinal behavior of itraconazole in humans - Part 1: Supersaturation
from a solid dispersion and a cyclodextrin-based solution.
AB - This study evaluated the fasted state gastrointestinal behavior of the lipophilic
drug itraconazole, orally administered to healthy volunteers as either a solid
dispersion (Sporanox(r) capsules) or a cyclodextrin-based solution (Sporanox(r)
solution). Following intake of the drug products, gastric and duodenal fluids
were aspirated and analyzed for itraconazole concentration, total content and
solubilizing capacity. Release of itraconazole from the solid dispersion
generated high and metastable supersaturated levels in the stomach, but the
dissolved fraction in the duodenum remained extremely low (median 2.5%). After
intake of the itraconazole solution, precipitation was limited in the stomach but
pronounced in the small intestine. Still, the dissolved fraction of itraconazole
in the duodenum (median 38%) appeared much higher than after intake of the solid
dispersion, possibly explaining the improved absorption of itraconazole from the
solution. As for the solid dispersion, the absorption-enabling ability of the
solution appeared mainly related to increased intraluminal concentrations by
means of supersaturation. Cyclodextrin-based solubilization of itraconazole
occurred only in the case of limited intraluminal dilution, but did not further
enhance itraconazole absorption. The obtained data will help to understand
critical aspects of supersaturating drug delivery systems and act as direct
reference for the optimization of in vitro simulation tools for gastrointestinal
drug behavior.
PMID- 28414136
TI - Highly efficient treatment of aerobic vaginitis with simple acidic buffered gels:
The importance of pH and buffers on the microenvironment of vaginas.
AB - Aerobic vaginitis (AV) leads to uterus deep infection or preterm birth.
Antibacterial agents are not optimal therapeutics of AV. Here, we report a series
of temperature-sensitive in situ forming acidic buffered gels for topical
treatment of AV, involving lactate, acetate, and citrate gels at pH 3.5, 5.0, and
6.5. AV rat models were prepared following vaginal infection with Staphylococcus
aureus and Escherichia coli. In vitro/in vivo studies of the buffered gels were
performed compared with ofloxacin gels and blank gels. All the buffered gels
showed the lower in vitro antibacterial activities than ofloxacin gels but the
better in vivo anti-S. aureus effects and similar anti-E. coli effects. The
buffered gels improved Lactobacillus growth in the vaginas. Both the healthy rat
vaginal pH and the pH of rat vaginas treated with the buffered gels were about
6.5 though the AV rat models or ones treated with ofloxacin gels still remained
at the high pH more than 7.0. After treatments with the buffered gels, the
vaginal smears changed to a clean state nearly without aerobic bacteria, the
vaginal tissues were refreshed, and the immunoreactions were downregulated. The
acidic buffered gels bring rapid decrease of local vaginal pH, high antibacterial
activities, improvement of probiotics, and alleviation of inflammation. They are
simple, highly efficient, and safe anti-AV formulations.
PMID- 28414137
TI - Novel dabigatran etexilate hemisuccinate-loaded polycap: Physicochemical
characterisation and in vivo evaluation in beagle dogs.
AB - The purpose of this study was to develop a novel dabigatran etexilate
hemisuccinate (DEH) salt-loaded polycap with bioequivalence to the dabigatran
etexilate mesylate (DEM)-loaded commercial product. DEH prepared with dabigatran
etexilate base (DE) and succinic acid was less hygroscopic but less soluble than
DEM. Numerous micronized DEHs and DEH-loaded solid dispersions were prepared
employing the spiral jet-milling and spray-drying techniques, respectively. Among
the formulations prepared, a micronized DEH prepared with the injection air at
1.5bar and the grinding air at 2bar, and a DEH-loaded solid dispersion prepared
with 6g HPMC most improved the drug solubility, respectively. Moreover, the
micronized DEH provided more increased drug solubility and dissolution compared
with the solid dispersion, even though its drug solubility was still lower than
that of DEM. Unlike the situation in other studies, the enhanced solubility and
dissolution of DEH was more due to particle size reduction than to a change to
the amorphous form. The micronized DEH prepared with Myrj 52S had greater drug
solubility than preparations with other surfactants. Among the organic acids
investigated, only fumaric acid (128.8mg) showed a similar pattern in pH changes
to the DEM-loaded commercial product. Furthermore, in order to make the
environment acidic while preventing the direct contact of the drug with fumaric
acid, the polycap was composed of a tablet containing the micronized DEH, Myrj
52S and other ingredients, and separate fumaric acid. This micronized DEH-loaded
polycap was dissolution- and bio-equivalent to the DEM-loaded commercial product
in beagle dogs. Thus, the novel micronized DEH-loaded polycap would be a
promising alternative to the DEM-loaded commercial product.
PMID- 28414138
TI - Apigenin, a modulator of PPARgamma, attenuates HFD-induced NAFLD by regulating
hepatocyte lipid metabolism and oxidative stress via Nrf2 activation.
AB - Lipid metabolic disorders and oxidative stress in the liver are key steps in the
progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk
factor for the development of metabolic syndrome. To date, no pharmacological
treatment for this condition has been approved. Our previous study has found that
the food-derived compound apigenin (Api) significantly attenuates obesity-induced
metabolic syndrome by acting as a peroxisome proliferator-activated receptor
gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was
used to dig out whether Api had the effect on NAFLD. The results showed that Api
had obvious effect in restraining NAFLD progression, including attenuating HFD
induced lipid accumulation and oxidative stress in vivo. As a PPARM, although Api
did significantly inhibit the expression of PPARgamma target genes encoding the
protein associated with lipid metabolism, it had no obvious activating effect on
PPARgamma. Interestingly, we found that Api promoted Nrf2 into the nucleus,
thereby markedly activating Nrf2 to inhibit the lipid metabolism related genes
and increase the oxidative stress related genes. Further Nrf2 knockdown/knockout
and overexpression experiments showed that Api regulating PPARgamma target genes
was dependent on Nrf2 activation and the activation of Nrf2 counteracted the
activation effect of PPARgamma by Api. Importantly, we also found that Api might
bind with Nrf2 via auto dock and ITC assay. Therefore, our results indicate that
Api ameliorates NAFLD by a novel regulating mode of Nrf2 and PPARgamma in
inhibiting lipid metabolism and oxidative stress abnormity.
PMID- 28414139
TI - Ligand-dependent and -independent regulation of human hepatic sphingomyelin
phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk
with liver X receptor.
AB - Pregnane X receptor (PXR) mainly regulates xenobiotic metabolism and
detoxification. Additionally, it exerts pleiotropic effects on liver physiology,
which in large parts depend on transrepression of other liver-enriched
transcription factors. Based on the hypothesis that lower expression levels of
PXR may reduce the extent of this inhibition, an exploratory genome-wide
transcriptomic profiling was performed using HepG2 cell clones with different
expression levels of PXR. This screen and confirmatory real-time RT-PCR
identified sphingomyelin phosphodiesterase acid-like (SMPDL) 3A, a novel
nucleotide phosphodiesterase and phosphoramidase, as being up-regulated by PXR
deficiency. Transient siRNA-mediated knock-down of PXR in HepG2 cells and primary
human hepatocytes similarly induced mRNA up-regulation, which translated into
increased intracellular and secreted extracellular protein levels. Interestingly,
ligand-dependent PXR activation also induced SMPDL3A in HepG2 cells and primary
human hepatocytes. Electrophoretic mobility shift assays and chromatin
immunoprecipitation demonstrated binding of PXR to the previously identified
liver X receptor (LXR)-binding DR4 motif as well as to an adjacent ER8 motif in
intron 1 of SMPDL3A. Constitutive binding of the unliganded receptor to the
intron 1 chromatin indicated ligand-independent repression of SMPDL3A by PXR.
Transient transfection and reporter gene analysis confirmed the specific role of
these motifs in PXR- and LXR-dependent activation of the SMPDL3A intronic
enhancer. PXR inhibited LXR mainly by competition for binding sites. In
conclusion, this study describes that a decrease in PXR expression levels and
ligand-dependent activation of PXR and LXR increase hepatic SMPDL3A levels, which
possibly connects these receptors to hepatic purinergic signaling and
phospholipid metabolism and may result in drug-drug interactions with
phosphoramidate pro-drugs.
PMID- 28414140
TI - Shear stress inhibits IL-17A-mediated induction of osteoclastogenesis via
osteocyte pathways.
AB - Interleukin (IL)-17 is crucial to osteoclast differentiation and activation.
Osteocytes support osteoclast formation and are thought to orchestrate bone
remodeling in response to fluid flow. The contribution of IL-17 to osteocyte
related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4
cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It
was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation,
enhanced expression of receptor activator of nuclear factor kappa-B ligand
(RANKL) and tumor necrosis factor-alpha (TNF-alpha), and induced
osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived
macrophage (BMM) cells. Additionally, shear stress upregulated osteoprotegerin
expression in osteocytes, downregulated the effect of IL-17A on RANKL and TNF
alpha expression, and attenuated IL-17A-activated osteoclastic differentiation in
the co-culture system of MLO-Y4 and BMM cells. Furthermore, we explored the
signaling pathways that potentially mediate these effects in osteocytes, and
found that the extracellular signal-regulated kinase (ERK)1/2 and signal
transducer and activator of transcription (STAT3) pathways were suppressed by IL
17A but induced by fluid flow. EphA2 signaling enhances osteoclastogenesis in
osteocytes, and the intercellular reversed EphA2-ephrinA2 signaling from
osteocytes to BMM play an important role in IL-17A-dependent osteoclastic
differentiation. EphB4 signaling inhibits osteoclastogenesis in osteocytes, and
the intercellular reversed EphB4-ephrinB2 signaling from osteocytes to BMM could
inhibit IL-17A-dependent osteoclastic differentiation. The current findings
suggest that IL-17A as a promoter of bone resorption and fluid shear stress
critically regulate bone remodeling via osteocyte-specific signaling pathways. IL
17 modulation-based approaches may be developed as a novel therapeutic strategy
for enhancing bone remodeling efficiency and stability.
PMID- 28414141
TI - Temporal role of macrophages in cancellous bone healing.
AB - Macrophages are important phagocytosing and cytokine producing cells with effects
on fracture healing. We used clodronate-containing liposomes to reduce the number
of macrophages, in order to study their role in the early phases of cancellous
bone healing. Holes were drilled bilaterally into the cancellous bone of the
proximal metaphysis of the tibia of 60 mice. A screw was inserted in the hole in
the right tibia. The day of surgery was day 0. Clodronate-containing liposomes
were injected intraperitoneally as a single injection either day -4 or -1 (before
surgery) or day 1 or 3 (after surgery). A control group underwent surgery as
above, but received no clodronate. The mice were killed day 7. The mechanical
quality of the new formed cancellous bone holding the screw was evaluated by a
pull-out test. The contents of the drill hole in the left tibia was analyzed by
microCT. Another set of 20 mice received a drill hole in the metaphysis of the
right tibia, and were given either clodronate or saline injections days -3 and
2. The animals were killed day 1 and 3. Flow cytometry was used to analyze the
composition of macrophage subpopulations in the regenerating tissue. Flow
cytometry showed that clodronate injections day -3 and -2 led to a decrease in
mature monocytes day 1 together with an increase in immature monocytes. On day 3
this effect had mostly disappeared, suggesting that the effect of the injections
lasted 3 to 5days. Mechanical testing revealed that the injections prior to
surgery decreased the strength of the new formed bone, holding the screw, by
about half. Bone density in the drill hole was similarly reduced. In contrast,
the injections given day 1 and 3 had smaller and statistically insignificant
effects. Since their depletion at later time points failed to produce a
significant effect, it seems that the role of macrophages in cancellous bone is
most crucial during the first two days after trauma.
PMID- 28414142
TI - Doxofylline does not increase formoterol-induced cAMP nor MKP-1 expression in ASM
cells resulting in lack of anti-inflammatory effect.
AB - The xanthine doxofylline has been examined in clinical trials and shown to have
efficacy and greater tolerability than theophylline in asthma and chronic
obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated
bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental
models of respiratory disease. However, there are limited studies in vitro. We
address this herein and examine whether doxofylline has anti-inflammatory impact
on primary cultures of airway smooth muscle (ASM) cells. We conduct a series of
investigations comparing and contrasting doxofylline with the archetypal
xanthine, theophylline, and the specific phosphodiesterase (PDE) 4 inhibitor,
cilomilast. We confirm that the xanthine drugs do not have action as PDE
inhibitors in ASM cells. Unlike cilomilast, doxofylline (and theophylline) do not
increase cAMP production in ASM cells induced by long-acting beta2-agonist
formoterol. Similar to theophylline, and consistent with the lack of cAMP
potentiation, doxofylline does not augment formoterol-induced upregulation of the
anti-inflammatory protein mitogen-activated protein kinase phosphatase 1 (MKP-1).
However, when we examine the effect of doxofylline on secretion of the
interleukin 8 from ASM cells stimulated by tumour necrosis factor (an in vitro
surrogate measure of inflammation), there was no repression of inflammation. This
is in contrast to the anti-inflammatory impact exerted by theophylline and
cilomilast in confirmatory experiments. In summary, our study is the first to
examine the effect of doxofylline on ASM cells in vitro and highlights some
distinct differences between two key members of xanthine drug family, doxofylline
and theophylline.
PMID- 28414143
TI - The Use of Hemoglobin Vesicles for Delivering Medicinal Gas for the Treatment of
Intractable Disorders.
AB - Bioactive gaseous molecules, such as oxygen (O2) and carbon monoxide (CO), are
essential elements for most living organisms to maintain their homeostasis and
biological activities. An accumulating body of evidence suggests that such
molecules can be used in clinics as a medical gas in the treatment of various
intractable disorders. Recent developments in hemoglobin-encapsulated liposomes,
namely hemoglobin vesicles (HbV), possess great potential for retaining O2 and CO
and could lead to strategies for the development of novel pharmacological agents
as medical gas donors. HbV with either O2 or CO bound to it has been demonstrated
to have therapeutic potential for treating certain intractable disorders and has
the possibility to serve as diagnostic and augmenting product by virtue of unique
physicochemical characteristics of HbV. The present review provides an overview
of the present status of the use of O2- or CO-binding HbV in experimental animal
models of intractable disorders and discusses prospective clinical applications
of HbV as a medical gas donor.
PMID- 28414144
TI - Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of
Preclinical and Clinical Findings.
AB - In recent years, an increasing number of clinical drug-drug interactions (DDIs)
have been attributed to inhibition of intestinal organic anion-transporting
polypeptides (OATPs); however, only a few of these DDI results were reflected in
drug labels. This review aims to provide a thorough analysis of intestinal OATP
mediated pharmacokinetic-based DDIs, using both in vitro and clinical
investigations, highlighting the main mechanistic findings and discussing their
clinical relevance. On the basis of pharmacogenetic and clinical DDI results, a
total of 12 drugs were identified as possible clinical substrates of OATP2B1 and
OATP1A2. Among them, 3 drugs, namely atenolol, celiprolol, and fexofenadine, have
emerged as the most sensitive substrates to evaluate clinical OATP-mediated
intestinal DDIs when interactions with P-glycoprotein by the test compound can be
ruled out. With regard to perpetrators, 8 dietary or natural products and 1
investigational drug, ronacaleret (now terminated), showed clinical intestinal
inhibition attributable to OATPs, producing >=20% decreases in area under the
plasma concentration-time curve of the co-administered drug. Common juices, such
as apple juice, grapefruit juice, and orange juice, are considered potent
inhibitors of intestinal OATP2B1 and OATP1A2 (decreasing exposure of the co
administered substrate by ~85%) and may be adequate prototype inhibitors to
investigate intestinal DDIs mediated by OATPs.
PMID- 28414146
TI - Tissue Distribution of a Therapeutic Monoclonal Antibody Determined by Large Pore
Microdialysis.
AB - Therapeutic monoclonal antibodies (mAbs) exhibit limited distribution to the
target tissues. Determination of target tissue interstitial concentration of mAbs
is an important aspect in the assessment of their
pharmacokinetic/pharmacodynamics relationship especially for mAbs targeting
membrane bound receptors. The pharmacokinetics of R7072, a full length mAb (IgG)
targeting human insulin-like growth factor-1 receptor was evaluated following a
single intravenous dose at 1, 6.25, and 25 mg/kg in healthy female SCID-beige
mice. R7072 showed linear pharmacokinetics over the dose range tested and was
characterized by low systemic clearance and long terminal half-life. Furthermore,
interstitial distribution of R7072 was evaluated in liver, skin, kidney, and
muscle tissues using large pore microdialysis (MD) after intravenous
administration of 10 mg/kg dose in mice. The relative recoveries of R7072 were
consistent and similar between in vitro and in vivo MD experiments. The tissue
and interstitial concentrations were significantly lower compared to serum
concentrations and found to be highest in liver and lowest in muscle. The
interstitial concentrations of R7072 were approximately 2-fold to 4-fold lower
than corresponding total tissue concentrations. Large pore MD appears to be an
attractive approach for direct measurement of pharmacologically relevant
concentrations of therapeutic mAbs in tissue interstitial fluid.
PMID- 28414147
TI - Public access to clinical trials: Lessons from an organizational implementation
of policy.
AB - Efforts to make clinical trials and their results more publicly available have
been increasing in recent years. However, there is a need to better understand
ways to achieve these goals aimed at benefiting a diverse set of stakeholders.
Since 2005, the U.S. Department of Veterans Affairs Office of Research and
Development (ORD), part of the nation's largest integrated health care system,
has required the clinical trials its funds to be registered in ClinicalTrials.gov
as a condition of the award. Furthermore, summary results of studies active since
2007 have been included in the registry. This paper highlights ORD activities,
challenges and lessons at investigator, study, and organizational levels. Key
factors in ORD's approach include: a mission-oriented approach; leadership
support; a working group for organizational policies and practices; prioritizing
communication; and recognizing the needs of investigators. Making clinical trials
available to the public should represent a focal point for groups desiring to
maximize the contributions from such research. The ability to do so must involve
a commitment by sponsors and a critical evaluation of the reasons, requirements
and resources at multiple levels.
PMID- 28414145
TI - Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative Phosphorus
(31P) Nuclear Magnetic Resonance Spectroscopy.
AB - The dialysis method is classically used for drug separation before analysis, but
does not provide direct and real-time drug quantification and has limitations
affecting the dialysis rate. In this study, a phosphorus nuclear magnetic
resonance (31P-qNMR) method is developed for the real-time quantification of
therapeutic molecules in vitro. The release kinetics of model drug, tenofovir
(anti-HIV microbicide), was analyzed in vaginal fluid simulant (VFS), seminal
fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ~100
200 nm) using the NMR (direct) method and compared with dialysis/UV-Vis
(indirect) method. The assay was linear in VFS/SFS (0.20-5.0 mM), HP (0.30-5.0 mM
of drug concentration range) and specific no drug 31P-qNMR chemical shift [~15
ppm] interference with formulation/media components. Limit of detection values
were 0.075/0.10/0.20 mM, whereas limit of quantification values were
0.20/0.20/0.30 mM in VFS/SFS/HP, respectively. The method was robust, precise
(%RSE <2%), and accurate (%mean recovery 90%-110%). After 12 h, ~77%/72%/70%
wt/wt of tenofovir release was observed with direct, compared to ~47%/52%/52%
wt/wt by indirect method in VFS/SFS/HP, respectively. Approximately 20% decrease
in %drug release observed with dialysis method suggested an interference with
drug transport process due to the dialysis membrane and the Gibbs-Donnan effect.
Overall, 31P-qNMR provides more accurate, real-time, and direct drug
quantification for effective in vitro-in vivo correlation.
PMID- 28414148
TI - A close collaboration of chitosan with lipid colloidal carriers for drug delivery
applications.
AB - Chitosan and lipid colloids have separately shown a growing interest in the field
of drug delivery applications. Their success is mainly due to their interesting
physicochemical behaviors, as well as their biological properties such as
bioactivity and biocompatibility. While chitosan is a well-known cationic
polysaccharide with the ability to strongly interact with drugs and biological
matrices through mainly electrostatic interactions, lipid colloids are carriers
particularly recognized for the drug vectorization. In recent years, the
combination of both entities has been considered because it offers new systems
which gather the advantages of each of them to efficiently deliver various types
of bioactive species. The purpose of this review is to describe these
associations between chemically-unmodified chitosan chains (solubilized or
dispersed) and lipid colloids (as nanoparticles or organized in lipid layers), as
well as their potential in the drug delivery area so far. Three assemblies have
mainly been reported in the literature: i) lipid nanoparticles (solid lipid
nanoparticles or nanostructured lipid carriers) coated with chitosan chains, ii)
lipid vesicles covered with chitosan chains, and iii) chitosan chains structured
in nanoparticles with a lipid coating. Their elaboration processes, their
physicochemical characterization, and their biological studies are detailed and
discussed herein. The different bioactive species (drugs and bio(macro)molecules)
incorporated in these assemblies, their maximal incorporation efficiency, and
their loading capacity are also presented. This review reveals the versatility of
these assemblies. Depending on the organization of lipids (i.e., nanoparticles or
vesicles) and the state of polymer chains (i.e., solubilized or dispersed under
the form of nanoparticles), a large variety of drugs can be successfully
incorporated, and various routes of administration can be considered.
PMID- 28414149
TI - Nanosystem trends in drug delivery using quality-by-design concept.
AB - Quality by design (QbD) has become an inevitable trend because of its benefits
for product quality and process understanding. Trials have been conducted using
QbD in nanosystems' optimization. This paper reviews the application of QbD for
processing nanosystems and summarizes the application procedure. It provides
prospective guidelines for future investigations that apply QbD to nanosystem
manufacturing processes. Employing the QbD concept in this way is a novel area in
nanosystem quality.
PMID- 28414150
TI - Supramolecular nanoparticles of calcitonin and dipeptide for long-term controlled
release.
AB - Salmon calcitonin (sCT) is a therapeutic polypeptide drug widely used to treat
bone diseases such as osteoporosis (more than 200 million patients all over the
world). The half-life of sCT is very short (~1h), thus various delivery systems
have been developed for sCT in order to avoid frequent injections. However, most
delivery systems use polymeric materials, which may limit their applications in
clinic formulations due to the biocompatibility issue. We observed that a very
simple dipeptide (Asp-Phe, DF) was co-assembled with sCT into supramolecular
nanoparticles. These nanoparticles can significantly prolong the acting time of
sCT to beyond one month after just a single subcutaneous injection. The
assembling and releasing mechanisms were thoroughly investigated by both in vitro
and in vivo methods, as well as by molecular dynamics simulations. This work
provides an alternative strategy of designing protein/peptide drug delivery
systems with long-lasting therapeutic effects.
PMID- 28414151
TI - Targeted antigen delivery to dendritic cell via functionalized alginate
nanoparticles for cancer immunotherapy.
AB - The purpose of the present study was to identify an "easy-to-adopt" strategy to
enhance immune responses using functionalized alginate (ALG) nanoparticles (MAN
ALG/ALG=OVA NPs), which were prepared by CaCl2 cross-linking of two different
types of ALG. The mannose (MAN) modified ALG (MAN-ALG) was used for dendritic
cell targeting. The other component, composed of ovalbumin (OVA), a model
antigen, is conjugated to ALG (ALG=OVA) via pH sensitive Schiff base bond.
Grafting of alginate was demonstrated by FT-IR and 1H NMR, while the
morphological structure, particle size, Zeta potential of MAN-ALG/ALG=OVA NPs
were measured using TEM and DLS. The OVA releasing behavior of MAN-ALG/ALG=OVA
NPs was determined as a function of pH. Antigen uptake was examined by flow
cytometry and confocal laser scanning microscopy in vitro using mouse bone marrow
dendritic cells (BMDCs). The results showed that MAN-ALG/ALG=OVA NPs facilitated
antigen uptake of BMDCs and cytosolic release of the antigen. Significant up
regulation of cytokine secretion and expression levels of the surface co
stimulatory molecules were also observed in MAN-ALG/ALG=OVA NPs-treated BMDCs,
compared to free OVA. In vivo bio-distribution study using Cy7 (a near-infrared
fluorescence dye) labeled MAN-ALG/ALG=OVA NPs showed efficient in vivo
trafficking of the nanoparticles from the injection site to the draining lymph
nodes. Moreover, MAN-ALG/ALG=OVA NPs were found to enhance cross-presentation of
OVA to B3Z T cell hybridoma in vitro. Subcutaneous administration of MAN
ALG/ALG=OVA NPs also induced major cytotoxic T lymphocytes (CTL) response and
inhibition of E.G7 tumor growth in C57BL/6 mice. In summary, we report here that
the MAN-ALG/ALG=OVA NPs have the potential as a potent nanovaccine for cancer
immunotherapy.
PMID- 28414152
TI - Rituximab for immunologic renal disease: What the nephrologist needs to know.
AB - Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used
in immune-mediated renal diseases. While licensed in the induction treatment of
ANCA-associated vasculitis, it represents one of the most commonly prescribed off
label drugs. Much of the information regarding its safety has been drawn from
experience in hematology and rheumatology. Ample evidence illustrates the safety
of RTX, however, rare but serious adverse events have emerged that include
progressive multifocal leucoencephalopathy and hepatitis B reactivation. Moderate
to severe hypogammaglobulinemia and late-onset neutropenia following RTX therapy
confer an increased infectious risk and factors predicting these side effects
(i.e. a genetic basis) need to be identified. Nephrologists initiating RTX need
to bear in mind that long-term risks and optimal dosing for many renal
indications remain unclear. Special considerations must be given when RTX is used
in women of childbearing age. We summarize practical aspects concerning the use
of RTX. This review will provide nephrologists with information to guide their
use of RTX alerting them to safety risks and the need for patient counselling.
PMID- 28414153
TI - Inflammatory myopathy associated with myasthenia gravis with and without thymic
pathology: Report of four cases and literature review.
AB - INTRODUCTION: The association of myasthenia gravis (MG) and inflammatory myopathy
is rare and often only one of the diseases is diagnosed. Thymus pathology may be
in the origin of such disease association. METHODS: We described four patients
with both MG and inflammatory myopathy. RESULTS: These cases correspond to 2.3%
of our MG cohort. Case 1: MG, polymyositis and thymolipoma; case 2: MG and
necrotizing myopathy without thymic pathology on a background of scleroderma,
Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
(CREST); case 3: MG and dermatomyositis without thymic pathology; case 4: MG and
dermatomyositis with type C thymoma. DISCUSSION: The recognition of these
neuromuscular co-morbidities contributes to (i) understanding their pathogenic
mechanisms, (ii) developing better management approaches and (iii) further
improving disease outcomes.
PMID- 28414154
TI - Targeting synovial neoangiogenesis in rheumatoid arthritis.
AB - In Rheumatoid arthritis (RA), neoangiogenesis is an early and crucial event to
promote the development of the hyperplasic proliferative pathologic synovium.
Endothelial cells are critical for the formation of new blood vessels since they
highly contribute to angiogenesis and vasculogenesis. Current therapies in RA
target the inflammatory consequences of autoimmune activation and despite major
improvements these last years still refractory patients or incomplete responders
may be seen raising the point of the need to identify complementary additive and
innovative therapies. This review resumes the mechanisms of synovial
neoangiogenesis in RA, including recent insights on the implication of
vasculogenesis, and the regulation of synovial neoangiogenesis by angiogenic and
inflammatory mediators. In line with the recent development of vascular-targeted
therapies used in cancer and beyond, we also discuss possible therapeutic
implications in RA, in particular the combination of targeted immunotherapies
with anti-angiogenic molecules.
PMID- 28414155
TI - Recent advances in cochlear hair cell regeneration-A promising opportunity for
the treatment of age-related hearing loss.
AB - The objective of this paper is to review current information regarding the
treatment of age-related hearing loss by using cochlear hair cell regeneration.
Recent advances in the regeneration of the inner ear, including the usefulness of
stem cells, are also presented. Based on the current literature, cochlear cell
regeneration may well be possible in the short term and cochlear gene therapy may
also be useful for the treatment of hearing loss associated with ageing. The
present review provide further insight into the pathogenesis of Inner Ear
senescence and aged-related hearing loss and facilitate the development of
therapeutic strategies to repair hair cells damaged by ageing. More research will
be needed in order to translate them into an effective treatment for deafness
linked to cochlear senescence in humans.
PMID- 28414156
TI - Modeling of interactions between functional domains of ALDH1L1.
AB - ALDH1L1, a member of the aldehyde dehydrogenase superfamily of enzymes, catalyzes
the conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. The
enzyme is a tetramer of identical subunits, with each subunit consisting of three
functional domains that originated from unrelated genes. The N- and C-terminal
domains are catalytic, while the intermediate domain transfers the reaction
intermediate from the N- to the C-terminal domain. The intermediate domain is an
acyl carrier protein, possessing the covalently attached 4'-phosphopantetheine (4
PP) prosthetic group. This prosthetic group is known to function as a swinging
arm transferring intermediates between enzymes in complex biosynthetic reactions.
Here we have applied computer modeling using available structures of the three
functional domains of ALDH1L1 to evaluate the extent of flexibility within the
full-length protein. This approach allowed us to define positions of the 4-PP arm
within the two catalytic domains and to predict N-terminal:intermediate and
intermediate:C-terminal domain interfaces. Our models further suggested high
degree of flexibility within the full-length enzyme.
PMID- 28414157
TI - Commiphora molmol resin attenuates diethylnitrosamine/phenobarbital-induced
hepatocarcinogenesis by modulating oxidative stress, inflammation, angiogenesis
and Nrf2/ARE/HO-1 signaling.
AB - The objective of the current study was to investigate the possible
chemopreventive activity of Commiphora molmol resin (myrrh) extract using a rat
model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced early stage
hepatocarcinogenesis. Here, we pointed to the modulatory effect of myrrh on
oxidative stress, angiogenesis, inflammation and nuclear factor (erythroid
derived 2)-like 2 (Nrf2). Hepatocarcinogenesis was induced in Wistar rats using
DEN for initiation and PB as a promoting agent. The rats received 125 or 250
mg/kg C. molmol resin extract throughout the experiment. Both doses of myrrh
improved liver function marker enzymes and prevented oval cells proliferation and
the distortion of hepatic architecture. The pro-inflammatory cytokine interleukin
6, tumor markers, angiogenesis markers, lipid peroxidation and nitric oxide (NO)
were significantly increased in DEN/PB-induced rats. In addition, the antioxidant
defenses showed marked reduction in the liver of DEN/PB-induced rats. Oral
administration of C. molmol extract to DEN/PB-induced rats significantly
decreased circulating markers of inflammation, tumor proliferation and
angiogenesis, and liver lipid peroxidation and NO. In addition, C. molmol
markedly ameliorated the antioxidant defenses and up-regulated Nrf2 and
hemeoxygenase (HO)-1 in the liver of DEN/PB-induced rats. In conclusion, these
results provide evidence that C. molmol resin has a potent chemopreventive
activity, possibly by up-regulating the Nrf2/HO-1 signaling and attenuation of
inflammation, angiogenesis and oxidative stress.
PMID- 28414158
TI - Methotrexate hepatotoxicity is associated with oxidative stress, and down
regulation of PPARgamma and Nrf2: Protective effect of 18beta-Glycyrrhetinic
acid.
AB - 18beta-glycyrrhetinic acid (18beta-GA) is a bioactive component of licorice with
promising hepatoprotective activity. However, its protective mechanism on
methotrexate (MTX) hepatotoxicity in not well defined. We investigated the
hepatoprotective effect of 18beta-GA, pointing to the role of peroxisome
proliferator activated receptor gamma (PPARgamma) and the redox-sensitive nuclear
factor erythroid 2-related factor 2 (Nrf2). Wistar rats were orally administered
18beta-GA (50 and 100 mg/kg) 7 days either before or after MTX injection. MTX
induced significant increase in circulating liver function marker enzymes and
bilirubin with concomitant declined albumin levels. Serum pro-inflammatory
cytokines, and liver malondialdehyde and nitric oxide were significantly
increased in MTX-induced rats. Treatment with 18beta-GA significantly reduced
serum enzymes of liver function, bilirubin and pro-inflammatory cytokines. 18beta
GA attenuated MTX-induced oxidative stress and restored the antioxidant defenses.
In addition, 18beta-GA improved liver histological structure and decreased the
expression of Bax whereas increased Bcl-2 expression. MTX-induced rats showed
significant down-regulation of Nrf2, hemoxygenase-1 and PPARgamma, an effect that
was markedly reversed by 18beta-GA supplemented either before or after MTX. In
conclusion, 18beta-GA protected against MTX-induced liver injury, possibly by
activating Nrf2 and PPARgamma, and subsequent attenuation of inflammation,
oxidative stress and apoptosis. Therefore, 18beta-GA can provide protection
against MTX-induced hepatotoxicity.
PMID- 28414159
TI - In vitro toxicological effects of zinc containing nanoparticles with different
physico-chemical properties.
AB - Nanomaterials (NM) exhibit novel physicochemical properties that determine their
interaction with biological substrates and processes. Recent nano-technological
advances are leading to wide usage of metallic nanoparticles (NPs) in various
fields. However, the increasing use of NPs has led to their release into
environment and the toxicity of NPs on human health has become a concern.
Moreover, there are inadvertently generated metallic NPs which are formed during
various human activities (e.g. metal processing and energy production).
Unfortunately, there are still widespread controversies and ambiguities with
respect to the toxic effects and mechanisms of metallic NPs, e.g. metal oxides
including ZnO. In this study, we generated zinc containing NMs, and studied them
in vitro. Different nano-sized particles containing Zn were compared in in vitro
study to elucidate the physicochemical characteristics (e.g. chemical
composition, solubility, shape and size of the particles) that determine cellular
toxicity. Zn induced toxicity in macrophage cell line (RAW 264.7) was detected,
leading to the cell cycle disruption, cell death and excitation of release of
inflammatory mediators. The solubility and the size of Zn compounds had a major
role in the induced toxic responses. The soluble particles reduced the cell
viability, whereas the less soluble NPs significantly increased inflammation.
Moreover, uptake of large ZnO NPs inside the cells was likely to play a key role
in the detected cell cycle arrest.
PMID- 28414160
TI - Paraquat induces extrinsic pathway of apoptosis in A549 cells by induction of DR5
and repression of anti-apoptotic proteins, DDX3 and GSK3 expression.
AB - Paraquat (PQ) is a bipyridyl derivative herbicide known to cause lung toxicity
partly through induction of apoptosis. Here we demonstrated that PQ caused
apoptosis in A549 cells. PQ increased cleavage of caspase-8 and Bid, indicating
caspase-8 activation and truncated Bid, the two key mediators of extrinsic
apoptosis. Additionally, PQ treatment caused an increase in DR5 (death receptor
5) and caspase-8 interaction, indicating formation of DISC (death-inducing
signaling complex). These results indicate that PQ induces apoptosis through
extrinsic pathway in A549 cells. Moreover, PQ drastically increased DR5
expression and membrane localization. Furthermore, PQ caused prominent
concentration dependent reductions of DDX3 (the DEAD box protein-3) and GSK3
(glycogen synthase kinase-3) which can associate with DR5 and prevent DISC
formation. Additionally, PQ decreased DR5-DDX3 interaction, suggesting a
reduction of DDX3/GSK3 anti-apoptotic complex. Inhibition of GSK3, which is known
to promote extrinsic apoptosis by its pharmacological inhibitor, BIO accentuated
PQ-induced apoptosis. Moreover, GSK3 inhibition caused a further decrease in PQ
reduced DR5-DDX3 interaction. Taken together, these results suggest that PQ may
induce extrinsic pathway of apoptosis in A549 cells through upregulation of DR5
and repression of anti-apoptotic proteins, DDX3/GSK3 leading to reduction of anti
apoptotic complex.
PMID- 28414161
TI - Metabolism of okadaic acid by NADPH-dependent enzymes present in human or rat
liver S9 fractions results in different toxic effects.
AB - The lipophilic marine biotoxin okadaic acid (OA) represents a natural contaminant
produced by algae accumulating in seafood. Acute intoxications result in
diarrhetic shellfish poisoning causing symptoms like nausea, vomiting and
abdominal cramps. OA was preincubated with liver enzymes present in S9 fractions
from humans, rats and rats pretreated with enzyme inducers in the presence or
absence of the cofactor NADPH to investigate hepatic metabolism. Cytotoxicity was
examined in HepG2 cells and metabolites of OA were determined by LC-MS/MS. Strong
cytotoxicity was observed in HepG2 cells treated with OA that was preincubated in
S9 fractions without NADPH. However, neither metabolites nor a decrease of OA
itself were found. The addition of NADPH to the S9 fractions of rats resulted in
a decreased cytotoxicity of OA, but a stronger toxicity in HepG2 cells was
observed from OA preincubated in human S9 fractions with NADPH. Metabolite
profiles of each S9 mix revealed that higher amounts of detoxified metabolites
were formed by NADPH-dependent enzymes of rats compared to the same enzymes of
humans. These differences in OA detoxification by NADPH-dependent liver enzymes
of rats and humans may be of significance in the extrapolation of toxicological
data from animal models (rats to humans, for example).
PMID- 28414162
TI - Biological response of HeLa cells to gold nanoparticles coated with organic
molecules.
AB - In this work, gold nanospheres functionalized with low weight organic molecules
(4-aminothiphenol and cysteamine) were synthesized in a one-step method for their
in vitro cytotoxic evaluation on HeLa cells. To enhance the biocompatibility of
the cysteamine-capped GNPs, BSA was used due to its broad PH stability and high
binding affinity to gold nanoparticles. Besides, the widely reported silica
coated gold nanorods were tested here to contrast their toxic response against
our nanoparticles coated with organic molecules. Our results shown, the viability
measured at 1.9*10-5M did not show significant differences against negative
controls for all the samples; however, the metabolic activity of HeLa cells
dropped when they were exposed to silica gold nanorods in the range of
concentrations from 2.9*10-7M to 3.0*10-4M, while in the cases of gold
nanospheres, we found that only at concentrations below 1.9*10-5M metabolic
activity was normal. Our preliminary results did not indicate any perceivable
harmful toxicity to cell membrane, cytoskeleton or nucleus due to our nanospheres
at 1.9*10-5M. Additional test should be conducted in order to ensure a safe use
of them for biological applications, and to determine the extent of possible
damage.
PMID- 28414163
TI - Droplet digital PCR (ddPCR) vs quantitative real-time PCR (qPCR) approach for
detection and quantification of Merkel cell polyomavirus (MCPyV) DNA in formalin
fixed paraffin embedded (FFPE) cutaneous biopsies.
AB - BACKGROUND: Merkel cell polyomavirus (MCPyV) is associated with Merkel cell
carcinoma and high viral load in the skin was proposed as a risk factor for the
occurrence of this tumour. MCPyV DNA was detected, with lower frequency, in
different skin cancers but since the viral load was usually low, the real
prevalence of viral DNA could be underestimated. OBJECTIVE: To evaluate the
performance of two assays (qPCR and ddPCR) for MCPyV detection and quantification
in formalin fixed paraffin embedded (FFPE) tissue samples. METHODS: Both assays
were designed to simultaneous detection and quantification of both MCPyV as well
as house-keeping DNA in clinical samples. The performance of MCPyV quantification
was investigated using serial dilutions of cloned target DNA. We also evaluated
the applicability of both tests for the analysis of 76 FFPE cutaneous biopsies.
RESULTS: The two approaches resulted equivalent with regard to the
reproducibility and repeatability and showed a high degree of linearity in the
dynamic range tested in the present study. Moreover, qPCR was able to quantify
>=105 copies per reaction, while the upper limit of ddPCR was 104 copies. There
was not significant difference between viral load measured by the two methods The
detection limit of both tests was 0,15 copies per reaction, however, the number
of positive samples obtained by ddPCR was higher than that obtained by qPCR (45%
and 37% respectively). CONCLUSIONS: The ddPCR represents a better method for
detection of MCPyV in FFPE biopsies, mostly these containing low copies number of
viral genome.
PMID- 28414164
TI - A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for
treatment of refractory out hospital cardiac arrest: An observational study and
propensity analysis.
AB - BACKGROUND: Out of hospital cardiac arrest (OHCA) mortality rates remain very
high with poor neurological outcome in survivors. Extracorporeal cardiopulmonary
resuscitation (ECPR) is one of the treatments of refractory OHCA. This study used
data from the mobile intensive care unit (MOICU) as part of the emergency medical
system of Paris, and included all consecutive patients treated with ECPR
(including pre-hospital ECPR) from 2011 to 2015 for the treatment of refractory
OHCA, comparing two historical ECPR management strategies. METHODS: We
consecutively included refractory OHCA patients. In Period 1, ECPR was indicated
in selected patients after 30min of advanced life support; in- or pre-hospital
implementation depended on estimated transportation time and ECPR team
availability. In Period 2, patient care relied on early ECPR initiation after
20min of resuscitation, stringent patient selection, epinephrine dose limitation
and deployment of ECPR team with initial response team. Primary outcome was
survival with good neurological function Cerebral Performance Category score (CPC
score) 1 and 2 at ICU discharge or day 28. FINDINGS: A total of 156 patients were
included. (114 in Period 1 and 42 in Period 2). Baseline characteristics were
similar. Mean low-flow duration was shorter by 20min (p<0.001) in Period 2.
Survival was significantly higher in Period 2: 29% vs 8% (P<0.001), as confirmed
by the multivariate analysis and propensity score. When combining stringent
patient selection with an aggressive strategy, the survival rate increased to
38%. Pre-hospital ECPR implementation in itself was not an independent predictor
of improved survival, but it was part of the strategy in Period 2.
INTERPRETATION: Our data suggest that ECPR in specific settings in the management
of refractory OHCA is feasible and can lead to a significant increase in
neurological intact survivors. These data, however, need to be confirmed by a
large RCT.
PMID- 28414165
TI - Recognising out-of-hospital cardiac arrest during emergency calls increases
bystander cardiopulmonary resuscitation and survival.
AB - BACKGROUND: Initiation of early bystander cardiopulmonary resuscitation (CPR)
depends on bystanders' or medical dispatchers' recognition of out-of-hospital
cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA
recognition during the emergency call was associated with bystander CPR, return
of spontaneous circulation (ROSC), and 30-day survival. Our secondary aim was to
identify patient-, setting-, and dispatcher-related predictors of OHCA
recognition. METHODS: We performed an observational study of all OHCA patients'
emergency calls in the Capital Region of Denmark from 01/01/2013-31/12/2013.
OHCAs were collected from the Danish Cardiac Arrest Registry and the Mobile
Critical Care Unit database. Emergency call recordings were identified and
evaluated. Multivariable logistic regression analyses were applied to all OHCAs
and witnessed OHCAs only to analyse the association between OHCA recognition and
bystander CPR, ROSC, and 30-day survival. Univariable logistic regression
analyses were applied to identify predictors of OHCA recognition. RESULTS: We
included 779 emergency calls in the analyses. During the emergency calls, 70.1%
(n=534) of OHCAs were recognised; OHCA recognition was positively associated with
bystander CPR (odds ratio [OR]=7.84, 95% confidence interval [CI]: 5.10-12.05) in
all OHCAs; and ROSC (OR=1.86, 95% CI: 1.13-3.06) and 30-day survival (OR=2.80,
95% CI: 1.58-4.96) in witnessed OHCA. Predictors of OHCA recognition were
addressing breathing (OR=1.76, 95% CI: 1.17-2.66) and callers located by the
patient's side (OR=2.16, 95% CI: 1.46-3.19). CONCLUSIONS: Recognition of OHCA
during emergency calls was positively associated with the provision of bystander
CPR, ROSC, and 30-day survival in witnessed OHCA.
PMID- 28414166
TI - Evaluation and application of molecular genotyping on nosocomial pathogen
methicillin-resistant Staphylococcus aureus isolates in Guangzhou representative
of Southern China.
AB - Staphylococcus aureus is recognized as a typical food-born pathogen in food
safety, and its rapid detection and typing methods are in desperate need. To
study their evolution characteristics and drug resistance condition,
Staphylococci isolates were subject to the investigation. Strain identification
were subjected to standard procedures (colony morphology, Gram staining, Vitek 2
automated system and the API commercial kit), and fingerprinting was then
performed with RAPD-PCR amplification. In this study, 179 isolated staphylococci
were identified as MRSA. In addition, Staphylococci isolates were subjected to
three different fingerprinting system (ERIC2, AP1 and AP7) and then genotyped
based on significant diversities. Nosocomial epidemiology was then conducted
according to the fingerprint result. To sum up, the RAPD method subjected for
MRSA rapid genotyping have a broad application prospect in food safety and
epidemiology.
PMID- 28414167
TI - Inhibition of the mitochondrial respiratory chain in gills of Rhamdia quelen
experimentally infected by Pseudomonas aeruginosa: Interplay with reactive oxygen
species.
AB - It has long been recognized that there are several infectious diseases linked to
the impairment of enzymatic complexes of the mitochondrial respiratory chain,
with consequent production of reactive oxygen species (ROS), that contribute to
disease pathogenesis. In this study, we determined whether the inhibition on
mitochondrial respiratory chain might be considered a pathway involved in the
production of ROS in gills of Rhamdia quelen experimentally infected by P.
aeruginosa. The animals were divided into two groups with six fish each:
uninfected (the negative control group) and infected (the positive control
group). On day 7 post-infection (PI), animals were euthanized and the gills were
collected to assess the activities of complexes I-III, II and IV of the
respiratory chain, as well as ROS levels. The activities of complexes I-III, II
and IV of the respiratory chain in gills decreased, while the ROS levels
increased in infected compared to uninfected animals. Moreover, a significant
negative correlation was found between enzymatic activity of the complexes I-III
and IV related to ROS levels in P. aeruginosa infected animals, corroborating to
our hypothesis that inhibition on complexes of respiratory chain leads to ROS
formation. Also, microscopic severe gill damage and destruction of primary and
secondary lamellae were observed in infected animals, with the presence of
hyperplasia, leukocytic infiltration and telangiectasia. In summary, we have
demonstrated, for the first time, that experimental infection by P. aeruginosa
inhibits the activities of mitochondrial complexes of respiratory chain and,
consequently, impairs the cellular energy homeostasis. Moreover, the inhibition
on mitochondrial complexes I-III and IV are linked to the ROS production,
contributing to disease pathogenesis.
PMID- 28414168
TI - Decompression alone versus fusion for pyogenic spondylodiscitis.
AB - BACKGROUND CONTEXT: A spinal infection is a serious problem for a spine surgeon,
and there is currently much debate regarding how best to treat pyogenic
spondylodiscitis using antibiotics and the instrumentations that have been
developed to date. PURPOSE: The purpose of this study was to determine which
method is better for treating pyogenic spondylodiscitis. STUDY DESIGN: A
retrospective chart review was performed. PATIENT SAMPLE: Thirty-one patients
with pyogenic spondylodiscitis underwent surgical treatment between 2000 and 2016
at the authors' institution. OUTCOME MEASURES: Clinical outcomes were assessed
using a visual analog scale (VAS). We measured translation and rotation on
flexion and extension X-rays to identify instability. METHODS: Patients were
divided into two groups: Group I, decompression group; Group II, decompression
plus fusion group. Group I exhibited no instability according to a preoperative
radiographic study, whereas Group II exhibited instability. Both groups were
compared with respect to demographics and laboratory findings, including tests to
determine C-reactive protein (CRP) levels and erythrocyte sedimentation rates
(ESR), organisms, and the total duration of antibiotic treatment after the
operation. We compared the results of the preoperative, postoperative, and last
follow-up radiographic examinations of the sagittal alignment of the infected
segment. This study was supported by a clinical research fund (4,500 dollars)
from the National Health Insurance Service, Ilsan Hospital. RESULTS: A total of
31 patients were included; 22 (71%) were in Group I and 9 (29%) were in Group II.
On radiological examination, the mean preoperative translation and rotation
values in Group I were 2.45+/-1.22 mm and 5.64+/-1.98 degrees , and in Group II
were 5.35+/-1.65 mm and 12.01+/-4.22 degrees . At the last follow-up, the mean
translation and rotation values in Group I were 1.95+/-1.75 mm and 2.69+/-1.61
degrees , and in Group II were 1.77+/-1.02 mm and 3.44+/-2.07 degrees . Both
Groups I and II exhibited stability after the operation. No differences were
detected in preoperative ESR and CRP levels between the two groups. Group I,
compared with Group II, experienced a shorter duration of treatment with
antibiotics and normalization of ESR and CRP levels after the operation and a
shorter hospitalization period. CONCLUSIONS: If the appropriate antibiotics are
administered quickly when there is no instability, decompression alone is
effective; however, if instability is detected, decompression plus fusion can be
used to achieve stability.
PMID- 28414169
TI - A biomechanical investigation of different screw head designs for vertebral
derotation in scoliosis surgery.
AB - BACKGROUND CONTEXT: The posterior pedicle screw-rod system, which is widely used
to correct spinal deformities, achieves a good correction rate in the frontal and
coronal planes but not in the axial plane. Direct vertebral derotation (DVD) was
developed to correct axial plane deformities. However, the design of screw head
and body connection, in terms of monoaxial, polyaxial, and uniplanar screw, may
influence the efficiency of DVD. PURPOSE: This study compared the efficiency of a
newly designed uniplanar screw with that of monoaxial and polyaxial screws in the
DVD maneuver. STUDY DESIGN: A porcine spine model and monoaxial, polyaxial, and
uniplanar screws were used to examine the biomechanics of the DVD maneuver.
METHODS: Six T7-T13 porcine thoracic spine segments were used as test specimens
in this study. Pedicle screws were inserted in the left pedicles of the T9-T11
spinal segments and then connected with a rod. Three types of pedicle screws with
different screw head designs (monoaxial, polyaxial, and uniplanar) were employed
in this study. The material testing system (MTS) machine generated a rotational
moment through the derotational tube on the T10 (apical body) pedicle screw,
which simulated the motion applied during the surgical vertebral derotational
procedure. The pedicle strain and the kinematics of the vertebral body and
derotational tube were recorded to evaluate the derotational efficiency of
different pedicle screw head designs. RESULTS: The variances of the derotation
for the monoaxial, polyaxial, and uniplanar screws were 2.22 degrees +/-1.43
degrees , 32.23 degrees +/-2.26 degrees , and 4.75 degrees +/-1.60 degrees ,
respectively; the derotation efficiency was 0.65, 0.51, and 0.12, respectively,
when the torques of the spinal constructs reached 3 Nm. The rotational variance
of the polyaxial screw was statistically greater than that of the monoaxial and
uniplanar screws (p<.05). The maximum micro-strains of the pedicles for the
monoaxial, polyaxial, and uniplanar screws were 1,067.45+/-550.35, 747.68+/
393.56, and 663.55+/-271.04, respectively, with no statistically significant
differences (p>.05). CONCLUSIONS: The screw head design played an important role
in the efficiency and variance of the derotation during the DVD maneuver. The
derotational efficiency of the newly designed uniplanar screw was closer to that
of the monoaxial screw group than to that of the polyaxial screw group. The
polyaxial screw was inferior to DVD owing to a derotational variance between the
derotational tube and the apical body that was correlated with the range of
motion of the screw head. In the present study, the pedicle strain was similar in
all groups. However, the pedicle strain of the uniplanar screw group was lower
than that of the monoaxial screw group and was similar to that of the polyaxial
screw group when the angle of rotation of the apical body increased.
PMID- 28414170
TI - Importance of patient-reported individualized goals when assessing outcomes for
adult spinal deformity (ASD): initial experience with a Patient Generated Index
(PGI).
AB - BACKGROUND CONTEXT: Current metrics to assess patients' health-related quality of
life (HRQOL) may not reflect a true change in the patients' specific perception
of what is most important to them. PURPOSE: This study aimed to describe the
initial experience of a Patient Generated Index (PGI) in which patients create
their own outcome domains. STUDY DESIGN: This is a single-center prospective
study. PATIENT SAMPLE: Patients with adult spinal deformity (ASD) comprise the
study sample. OUTCOME MEASURES: Oswestry Disability Index (ODI), Short Form-36
(SF-36 Physical Component Score [PCS] and Mental Component Score [MCS]),
Scoliosis Research Society-22r (SRS-22r), and PGI. METHODS: Oswestry Disability
Index, SF-36, SRS-22r, and PGI were administered preoperatively and
postoperatively at 6 weeks, 3 months, 6 months, and 1 and 2 years. PGI
correlations with ODI, SF-36, SRS total score, free-text frequency analysis of
PGI exact response with text in ODI and SRS-22r questionnaires, and the
responsiveness (effect size [ES]) of the HRQOL metrics were analyzed. No funding
was used for this study and there are no conflicts of interest. RESULTS: A total
of 59 patients with 209 clinical encounters produced 370 PGI written response
topics that included affect or emotions, relationships, activities of daily life,
personal care, work, and hobbies. Mean preoperative PGI score was 18.6+/-13.5 (0
71.7 out of 100 [best]), and mean scores significantly improved at every
postoperative time point (p<.05). Preoperative PGI scores significantly
correlated with preoperative ODI (r=-0.28, p=.03), MCS (r=0.48, p<.01), and SRS
total (r=0.57, p<.01). Postoperative PGI scores correlated with all HRQOL
measures (p<.0001): ODI (r=-0.65), PCS (r=0.50), MCS (r=0.55), and SRS total
(r=0.63). PGI responses exactly matched ODI and SRS-22r text at 47.8% and 35.4%,
respectively, and at 63.2% and 58.9%, respectively, for categories. Patient
Generated Index ES at a minimum of 1-year follow-up was -2.39, indicating
substantial responsiveness (|ES|>0.8). Effect sizes for ODI, SRS-22r total, SF-36
PCS, and SF-36 MCS were 2.16, -2.06, -2.05, and -0.80, respectively. CONCLUSIONS:
The PGI is easy to administer and offers additional information about the
patients' perspective not captured in standard HRQOL metrics. Patient Generated
Index scores correlated with all of the standard HRQOL scores and were more
responsive than ODI, SF-36, and SRS-22r, suggesting that the PGI may be a step
closer to one HRQOL measure that better encompasses concerns and goals of the
individual patients.
PMID- 28414171
TI - The effects of water on degradation of the zirconia-resin bond.
AB - OBJECTIVES: 10-methacryloyloxydecyldihydrogenphosphate (MDP) containing primers
improve bonding of yttria-stabilised tetragonal zirconia (Y-TZP) to methacrylate
resins. The present study investigated the role played by water in the
deterioration of MDP-mediated zirconia-resin bonds. METHODS: Grit-blasted Y-TZP
plates were conditioned with two MDP primers and bonded with resin for shear bond
strength (SBS) testing. Additional bonded plates were aged hydrothermally and
compared with unaged Y-TZP after 24h of water-storage or 6 months of
water/acid/alkali-storage. The monoclinic phase (m-ZrO2) in different groups was
determined by X-ray diffraction. Hydrolytic stability of the coordinate bond
between MDP and zirconia in neutral/acid/alkaline environment was analysed using
thermodynamic calculations. Microleakage and release of the element phosphorus
from MDP-mediated Y-TZP/resin-bonded interfaces were evaluated via methylene blue
dye infiltration and inductively coupled plasma-mass spectrometry (ICP-MS).
RESULTS: Hydrothermal ageing did not significantly alter SBS. Ageing in acidic or
neutral medium led to significant decline in SBS. The m-ZrO2 phase increased
after hydrothermal ageing but no m-ZrO2 was detected in the water/acid/alkali
aged specimens. A higher equilibrium constant was identified in the MDP-t-ZrO2
complex when compared with the MDP-m-ZrO2 complex. MDP-conditioning failed to
prevent infiltration of the methylene blue dye. Phosphorus was detected by ICP-MS
from the solutions used for soaking the resin-bonded specimens. CONCLUSIONS:
Hydrolysis of the coordinate bond between MDP and ZrO2, rather than t->m phase
transformation, weakens the bond integrity between MDP-conditioned Y-TZP and
methacrylate resin. CLINICAL SIGNIFICANCE: Hydrolysis of the coordinate bond
between MDP and zirconia is responsible for deterioration of the integrity of the
bond between MDP-conditioned Y-TZP and methacrylate resin.
PMID- 28414172
TI - LCCL protein complex formation in Plasmodium is critically dependent on LAP1.
AB - Successful sporogony of Plasmodium berghei in vector mosquitoes requires
expression of a family of six modular proteins named LCCL lectin domain adhesive
like proteins (LAPs). The LAPs share a subcellular localization in the
crystalloid, a unique parasite organelle that forms during ookinete development.
Here, LAP interactions in P. berghei were studied using a series of parasite
lines stably expressing reporter-tagged LAPs combined with affinity purification
and high accuracy label free quantitative mass spectrometry. Our results show
that abundant complexes containing LAP1, LAP2 and LAP3 are formed in gametocytes
through high avidity interactions. Following fertilization, LAP4, LAP5 and LAP6
are recruited to this complex, a process that is facilitated by LAP1 chiefly
through its scavenger receptor cysteine-rich modules. These collective findings
provide new insight into the temporal and molecular dynamics of protein complex
formation that lead up to, and are required for, crystalloid biogenesis and
downstream sporozoite transmission of malaria parasites.
PMID- 28414173
TI - Affinity interactions drive post-implantation drug filling, even in the presence
of bacterial biofilm.
AB - : Current post-operative standard of care for surgical procedures, including
device implantations, dictates prophylactic antimicrobial therapy, but a
percentage of patients still develop infections. Systemic antimicrobial therapy
needed to treat such infections can lead to downstream tissue toxicities and
generate drug-resistant bacteria. To overcome issues associated with systemic
drug administration, a polymer incorporating specific drug affinity has been
developed with the potential to be filled or refilled with antimicrobials, post
implantation, even in the presence of bacterial biofilm. This polymer can be used
as an implant coating or stand-alone drug delivery device, and can be translated
to a variety of applications, such as implanted or indwelling medical devices,
and/or surgical site infections. The filling of empty affinity-based drug
delivery polymer was analyzed in an in vitro filling/refilling model mimicking
post-implantation tissue conditions. Filling in the absence of bacteria was
compared to filling in the presence of bacterial biofilms of varying maturity to
demonstrate proof-of-concept necessary prior to in vivo experiments. Antibiotic
filling into biofilm-coated affinity polymers was comparable to drug filling seen
in same affinity polymers without biofilm demonstrating that affinity polymers
retain ability to fill with antibiotic even in the presence of biofilm.
Additionally, post-implantation filled antibiotics showed sustained bactericidal
activity in a zone of inhibition assay demonstrating post-implantation capacity
to deliver filled antibiotics in a timeframe necessary to eradicate bacteria in
biofilms. This work shows affinity polymers can fill high levels of antibiotics
post-implantation independent of biofilm presence potentially enabling device
rescue, rather than removal, in case of infection. STATEMENT OF SIGNIFICANCE:
Post-operative prophylactic antimicrobial therapy greatly reduces risk of
infection, such as on biomedical implants, but does not totally eliminate
infections, and the healthcare cost of these remaining infections remains a major
concern. Systemic antimicrobial therapy to treat these infections can lead to
tissue toxicity and drug-resistant bacteria. In order to treat only those
patients who have developed infections, a customizable antimicrobial delivery
system made of cyclodextrin-based affinity polymer has been developed that is
capable of filling post-implantation and delivering the filled antibiotic in a
sustained manner even when the delivery device covered in bacterial biofilm.
These observations have the potential to be translated to a wide variety of
applications, such as implanted or indwelling medical devices, and/or surgical
site infections.
PMID- 28414174
TI - Iterative integration of multiple-copy pathway genes in Yarrowia lipolytica for
heterologous beta-carotene production.
AB - beta-Carotene is a terpenoid molecule with high hydrophobicity that is often used
as an additive in foods and feed. Previous work has demonstrated the heterologous
biosynthesis of beta-carotene from an intrinsic high flux of acetyl-CoA in 12
steps through 11 genes in Yarrowia lipolytica. Here, an efficient biosynthetic
pathway capable of producing 100-fold more beta-carotene than the baseline
construct was generated using strong promoters and multiple gene copies for each
of the 12 steps. Using fed-batch fermentation with an optimized medium, the
engineered pathway could produce 4g/L beta-carotene, which was stored in lipid
droplets within engineered Y. lipolytica cells. Expansion of these cells for
squalene production also demonstrated that Y. lipolytica could be an industrially
relevant platform for hydrophobic terpenoid production.
PMID- 28414175
TI - Success in the acquisition of Bombyx mori sperm motility is influenced by the
extracellular production of nitric oxide (NO) in the presence of seminal fluid
nitric oxide synthase (NOS).
AB - A trypsin-like protease called initiatorin is known to initiate sperm motility in
the silkworm, Bombyx mori, but little is known about the signaling events leading
to sperm flagellar beating. The aim of this study was to investigate whether this
mechanism of sperm motility activation involves the signaling transmitter nitric
oxide (NO). NO is produced from the amino acid L-arginine by the enzyme action of
nitric oxide synthase (NOS; EC 1.14.13.39). Simple treatment of quiescent sperm
with an NO donor (SNAP or NOC7) in vitro did not lead to activation of motility.
Nevertheless, initiatorin- or trypsin-induced motility was blocked by
pretreatment of sperm with either the NOS inhibitor L-NAME or NO scavenger
carboxy-PTIO. These observations suggested that NO may play important
physiological roles in the acquisition of sperm motility under the in vitro
condition used here. Then, we investigated whether NO synthesis would occur in
the spermatophore, a capsule containing spermatozoa that is created by the
contents of various male reproductive glands and is the site of sperm maturation.
The amounts of NO2- and NO3-, stable metabolites of NO, reached maximum values
after enclosure in the spermatophore, a time when apyrene spermatozoa acquire
vigorous motility. Moreover, RT-PCR and Western blotting analyses of NOS
indicated that it is abundantly expressed in glandula (g.) lacteola of the virgin
male ejaculatory duct, from which it is secreted to the seminal fluid and
transferred to the female during mating. Previous studies demonstrated that free
L-arginine is supplied de novo by a specific proteolytic reaction in which
initiatorin participates during spermatophore formation (Osanai et al., 1987c).
Based on these results, it can be presumed that the mixing of seminal fluid
contents from each male reproductive organ during ejaculation induced NO
production outside of the spermatid, and exogenous NO stimulated a signaling
pathway involved in the activation of silkworm apyrene sperm.
PMID- 28414176
TI - Genome specific PPARalphaB duplicates in salmonids and insights into estrogenic
regulation in brown trout.
AB - Peroxisome proliferator-activated receptors (PPARs) are key regulators of many
processes in vertebrates, such as carbohydrate and lipid metabolism. PPARalpha, a
member of the PPAR nuclear receptor gene subfamily (NR1C1), is involved in fatty
acid metabolism, namely in peroxisomal beta-oxidation. Two gene paralogues,
pparalphaA and pparalphaB, were described in several teleost species with their
origin dating back to the teleost-specific genome duplication (3R). Given the
additional salmonid-specific genome duplication (4R), four genes could be
theoretically anticipated for this gene subfamily. In this work, we examined the
pparalpha gene repertoire in brown trout, Salmo trutta f. fario. Data disclosed
two pparalpha-like sequences in brown trout. Phylogenetic analyses further
revealed that the isolated genes are most likely genome pparalphaB duplicates,
pparalphaBa and pparalphaBb, while pparalphaA is apparently absent in salmonids.
Both genes showed a ubiquitous mRNA expression across a panel of 11 different
organs. In vitro exposed primary brown trout hepatocytes strongly suggest that
pparalpha gene paralogues are differently regulated by ethinylestradiol (EE2).
PparalphaBb mRNA expression significantly decreased with dosage, reaching
significance after exposure to 50MUM EE2, while pparalphaBa mRNA increased,
significant at 1MUM EE2. The present data enhances the understanding of pparalpha
function and evolution in teleost, and reinforces the evidence of a potential
crosstalk between estrogenic and pparalpha signaling pathways.
PMID- 28414177
TI - The acitretin and methotrexate combination therapy for psoriasis vulgaris
achieves higher effectiveness and less liver fibrosis.
AB - Both acitretin and methotrexate are effective in ameliorating psoriatic lesion.
However, their combination has been seldom reported in the treatment of psoriasis
because of the warning regarding the potential hepatotoxicity of the drug
interactions. This study was designed to investigate the effectiveness of such
combination therapy for psoriasis vulgaris, and the potential benefit as well as
side effect during the treatment. Thirty-nine patients with psoriasis vulgaris
were treated with acitretin, methotrexate or their combination or as control.
Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs.
Human primary keratinocytes and hepatic stellate cells were used for analyzing
their effect in vitro. The results showed that the combination therapy exhibited
higher effectiveness in remitting skin lesion, but did not significantly affect
the liver function of both patients and mice. Moreover, the combination groups
showed less elevation of profibrotic factors in sera when compared with
methotrexate alone groups accordingly. Furthermore, primary keratinocytes
expressed more involucrin as well as loricrin and proliferated more slowly on the
combined stimulation. Interestingly, such combination treatment induced lower
expression of profibrotic factors in hepatic stellate cells. In conclusion, the
acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve
higher effectiveness and result in less liver fibrosis.
PMID- 28414178
TI - Short- and long-term effects of risperidone on catalepsy sensitisation and
acquisition of conditioned avoidance response: Adolescent vs adult rats.
AB - The effects of antipsychotic drugs (APDs) on the adolescent brain are poorly
understood despite a dramatic increase in prescription of these drugs in
adolescents over the past twenty years. Neuronal systems continue to be remodeled
during adolescence. Therefore, when given in adolescence, antipsychotic drugs
(APDs) have the potential to affect this remodeling. In this study we
investigated the effects of chronic 22-day risperidone treatment (1.3mg/kg/day)
in both adolescent and adult rats. We examined short- and long-term changes in
behaviour (catalepsy, locomotion and conditioned avoidance response (CAR)), and
dopaminergic and serotonergic neurochemistry in the striatum and the nucleus
accumbens. Here, we report that, both during chronic treatment and after a
lengthy drug-free interval, risperidone induced a sensitised cataleptic response
regardless of the age of exposure. Selectively in adolescents, risperidone
induced catalepsy was inversely correlated with striatal dopamine turnover
immediately after chronic treatment. After a drug-free interval, a significant
proportion of rats with prior adolescent risperidone treatment also failed to
acquire CAR to a defined criterion. Our data provide evidence that the same
chronic risperidone treatment regimen can induce contrasting short- and long-term
neural outcomes in the adolescent and adult brains.
PMID- 28414179
TI - Alteration of B cell subsets and the receptor for B cell activating factor (BAFF)
in paediatric patients with type 1 diabetes.
AB - BACKGROUND: Lately, mounting evidence has shown that B cells play an important
role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations
in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of
patients with type 1 diabetes (T1D) and their relatives. PATIENTS AND METHODS: B
cells were studied in 438 patients with T1D (158 at disease onset and 280 with
long-term disease), 136 first-degree relatives and 53 healthy controls. The B
cell panel included transitional, naive, MZ-like, switched memory B cells and
plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on
both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was
analysed in vitro. RESULTS: We observed a significant decrease in the proportion
of transitional B cells in the patients with T1D, accompanied by an increased
proportion of plasmablasts, especially in recent-onset patients and their
relatives. While the BAFF serum levels did not differ in the patients with T1D,
BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort,
with the exception of patients with recent-onset disease who exhibited a
significant increase in the number of BAFFR-expressing T cells. T cell activation
and B cell proliferation were more pronounced after activation with BAFF in the
T1D cohort compared to controls. CONCLUSION: The B cell panel in patients with
T1D is characterized by significantly reduced populations of B cells in their
early stages of development with a shift towards plasma cells. The dynamics of
BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D
T cells to BAFF point to the role of BAFF and T and B cell cooperation in the
development of T1D.
PMID- 28414180
TI - Serum TNF-alpha concentrations in type 2 diabetes mellitus patients and diabetic
nephropathy patients: A systematic review and meta-analysis.
AB - OBJECTIVES: The aim of this study was to investigate whether the concentrations
of serum tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine,
increased in type 2 diabetes mellitus (T2DM) and type 2 diabetic nephropathy
(T2DN) patients. METHODS: The four databases (PubMed, CNKI, WanFang and Chinese
Cqvip) were searched from Jan 1, 1999 to October 1, 2016 for all clinical case
control studies about the serum TNF-alpha concentrations in T2DM and T2DN
patients. All relevant data were extracted from published reports. The meta
analysis was performed to compare the changes of serum TNF-alpha concentrations
of T2DN and T2DM patients in Eastern and Western with healthy controls. We
further evaluated concentrations of serum TNF-alpha in T2DN patients with
mincroalbuminuria or macroalbuminuria. Random-effects models were adopted to
assess the pooling data among various variations. RESULTS: In total of 6 studies
(744 patients and 277 healthy controls) were included in this study. Compared
with healthy controls (both p<0.01), the groups of different albuminuria levels
and ethnicities both showed that the serum TNF-alpha levels were significantly
elevated in T2DN patients as well as in eastern T2DN patients (p=0.001), but not
significant changed in western T2DN patients (p=0.081). The results were stable
through sensitivity analysis and no significant publications bias existed in this
meta-analysis. CONCLUSIONS: Serum TNF-alpha concentrations are obviously
increased in T2DN and T2DM patients, but higher in T2DN patients, suggesting an
elevated inflammatory burden in T2DN patients.
PMID- 28414181
TI - Myeloid but not plasmacytoid blood DCs possess Th1 polarizing and Th1/Th17
recruiting capacity in psoriasis.
AB - Psoriasis is a common inflammatory skin disease and dendritic cells (DCs) play
crucial role in the development of skin inflammation. Although the
characteristics of skin DCs in psoriasis are well defined, less is known about
their peripheral blood precursors. Our aim was to characterize the phenotypic
features as well as the cytokine and chemokine production of CD1c+ myeloid DCs
(mDCs) and plasmacytoid DCs (pDCs) in the blood samples of psoriatic patients.
Blood DCs were isolated by using a magnetic separation kit, and their
intracytoplasmic cytokine production and CD83/CD86 maturation/activation marker
expression were investigated by 8-colour flow cytometry. In CD1c+ mDCs the
intracellular productions of Th1, Th2, Th17, Th22 and Treg polarizing cytokines
were examined simultaneously, whereas in pDCs the amounts of IFNalpha as well as
IL-12, IL-23 and IL-6 were investigated. The chemokine production of both DC
populations was investigated by flow-cytometry and ELISA. According to our
results psoriatic CD1c+ mDCs were in a premature state since their CD83/CD86
maturation/activation marker expression, IL-12 cytokine, CXCL9 and CCL20
chemokine production was significantly higher compared to control cells. On the
other hand, blood pDCs neither produced any of the investigated cytokines and
chemokines nor expressed CD83/CD86 maturation/activation markers. Our results
indicate that in psoriasis not only skin but also blood mDCs perform Th1
polarizing and Th1/Th17 recruiting capacity, while pDCs function only in the skin
milieu.
PMID- 28414182
TI - Innate lymphoid cells and their stromal microenvironments.
AB - In addition to the interaction between antigen presenting cells, T and B
lymphocytes, recent studies have revealed important roles for a diverse set of
auxiliary cells that profoundly influence the induction and regulation of immune
responses against pathogens. Of these the stromal cells composed of various non
hematopoietic constituents are crucial for the creation and maintenance of
specialized semi-static three-dimensional lymphoid tissue microenvironment,
whereas the more recently described innate lymphoid cells are generated by the
diversification of committed lymphoid precursor cells independently from clonally
rearranged antigen receptor genes. Recent findings have revealed important
contributions by innate lymphoid cells in inflammation and protection against
pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also
influence the onset of immune responses in tissue-specific fashion, raising the
possibility of tissue-specific stromal - innate lymphoid cell collaboration. In
this review we summarize the main features and interactions between these two
cells types, with particular emphasis on ILC type 3 cells and their
microenvironmental partners.
PMID- 28414183
TI - NKG2D: A versatile player in the immune system.
AB - NKG2D is known as a potent activating receptor of the immune system. It is
expressed on a multitude of immune cells, including NK cells and different
subsets of T cells. NKG2D recognizes various MHC I-like ligands that are induced
on target cells exposed to stressors such as viral infection, DNA damage and
oncological transformation. NKG2D drives or facilitates cytotoxic and cytokine
responses towards cells expressing its ligands to eliminate the threat.
Therefore, NKG2D is usually classified as a sensor that translates cellular
stress into activation signals for immune cells. However, more recently it has
become evident that NKG2D plays a role beyond direct killing of target cells.
Lack of NKG2D affects development of NK cells in the bone marrow, resulting in
hyperreactive NK cells. NKG2D deficiency on CD8 T cells affects the ability of
effector cells to produce cytokines in response to T cell receptor engagement and
reduces their capacity to establish immunological memory. Although NKG2D is not
expressed on B cells subsets, lack of this receptor in hematopoietic precursors
affects B cell development. Homing of mature B2 cells is altered in NKG2D
deficient mice and they have a strong reduction in peripheral B1a cell numbers,
resulting in increased susceptibility to bacterial infections. The exact
molecular mechanisms via which NKG2D mediates these versatile functions is still
being explored, but appears to depend on the control of activation thresholds,
either in hematopoietic precursors or mature immune cell subsets. In this review,
we will elaborate on the underappreciated developmental and regulatory roles of
NKG2D.
PMID- 28414184
TI - Mouse cytomegalovirus encoded immunoevasins and evolution of Ly49 receptors -
Sidekicks or enemies?
AB - Cytomegaloviruses (CMVs) have dedicated a large portion of their genome towards
immune evasion targeting many aspects of the host immune system, particularly NK
cells. However, the host managed to cope with the infection by developing
multiple mechanisms to recognize viral threat and counterattack it, thus
illustrating never-ending evolutionary interplay between CMV and its host. In
this review, we will focus on several mechanisms of NK cell evasion by mouse CMV
(MCMV), the role of host inhibitory and activating Ly49 receptors involved in the
virus control and acquisition of adaptive features by NK cells as a consequence
of MCMV infection.
PMID- 28414185
TI - Individual differences in the dominance of interhemispheric connections predict
cognitive ability beyond sex and brain size.
AB - Global structural brain connectivity has been reported to be sex-dependent with
women having increased interhemispheric connectivity (InterHc) and men having
greater intrahemispheric connectivity (IntraHc). However, (a) smaller brains show
greater InterHc, (b) larger brains show greater IntraHc, and (c) women have, on
average, smaller brains than men. Therefore, sex differences in brain size may
modulate sex differences in global brain connectivity. At the behavioural level,
sex-dependent differences in connectivity are thought to contribute to men-women
differences in spatial and verbal abilities. But this has never been tested at
the individual level. The current study assessed whether individual differences
in global structural connectome measures (InterHc, IntraHc and the ratio of
InterHc relative to IntraHc) predict spatial and verbal ability while accounting
for the effect of sex and brain size. The sample included forty men and forty
women, who did neither differ in age nor in verbal and spatial latent components
defined by a broad battery of tests and tasks. High-resolution T1-weighted and
diffusion-weighted images were obtained for computing brain size and
reconstructing the structural connectome. Results showed that men had higher
IntraHc than women, while women had an increased ratio InterHc/IntraHc. However,
these sex differences were modulated by brain size. Increased InterHc relative to
IntraHc predicted higher spatial and verbal ability irrespective of sex and brain
size. The positive correlations between the ratio InterHc/IntraHc and the spatial
and verbal abilities were confirmed in 1000 random samples generated by
bootstrapping. Therefore, sex differences in global structural connectome
connectivity were modulated by brain size and did not underlie sex differences in
verbal and spatial abilities. Rather, the level of dominance of InterHc over
IntraHc may be associated with individual differences in verbal and spatial
abilities in both men and women.
PMID- 28414187
TI - Metatropic dysplasia in third trimester of pregnancy and a novel causative
variant in the TRPV4 gene.
AB - Prenatal diagnosis of skeletal dysplasias is particularly difficult for many
reasons and differentiating these disorders in the prenatal period can be
challenging because they are rare and many of the ultrasound findings are not
necessarily pathognomonic for a specific disorder. The diagnosis is often made
just after birth or exitus. The prenatal diagnosis of osteochondrodysplasias is
based predominantly upon fetal ultrasound findings and it focuses substantially
on the possible lethality of the disorder, without always being able to find a
specific name for the disorder. Metatropic dysplasia is a rare
osteochondrodysplasia due to mutations in the TRPV4 gene: TRPV4 is a cation
channel, non-selectively permeable to calcium, encoded by a gene on chromosome
12q24.11; it is widely expressed and involved in many different physiological
processes through responses to several different stimuli (physical, chemical, and
hormonal) in ciliated epithelial cells. The exact incidence of this disorder is
not known, however less than a hundred cases have been reported at present, with
only two prenatal reports but without any reference to the molecular test. We
describe the first report of molecular diagnosis of metatropic dysplasia carried
out in prenatal diagnosis: the molecular testing of the TRPV4 (transient receptor
potential cation channel, subfamily V, member 4, MIM *605427) gene in our case,
in fact, detected a causative variant, confirming the diagnostic suspicion, which
was made possible thanks also to the utilization of MRI and CT scan. In our case
different imaging methods together with the close cooperation of a
multidisciplinary team and test availability, allowed an accurate diagnosis.
PMID- 28414188
TI - A case of splenomegaly in CBL syndrome.
AB - INTRODUCTION: We present a child with unexplained splenomegaly to highlight this
feature as a presenting sign of the RASopathy CBL syndrome and to draw attention
to the power and utility of next generation genomic sequencing for providing
rapid diagnosis and critical information to guide care in the pediatric clinical
setting. CLINICAL REPORT: A 7-year-old boy presented with unexplained
splenomegaly, attention deficit hyperactivity disorder, mild learning
difficulties, easy bruising, mild thrombocytopenia, and subtle dysmorphic
features. Extensive haematological testing including a bone marrow biopsy showed
mild megaloblastoid erythropoiesis and borderline fibrosis. There were no
haematological cytogenetic anomalies or other haematological pathology to explain
the splenomegaly. Metabolic testing and chromosomal microarray were unremarkable.
Trio whole-exome sequencing (WES) identified a pathogenic de novo heterozygous
germline CBL variant (c.1111T > C, p.Y371H), previously reported to cause CBL
syndrome and implicated in development of juvenile myelomonocytic leukemia
(JMML). DISCUSSION: CBL syndrome (more formally known as "Noonan-syndrome-like
disorder with or without juvenile myelomonocytic leukemia") has overlapping
features to Noonan syndrome with significant variability. CBL syndrome and other
RASopathy disorders-including Noonan syndrome, neurofibromatosis 1, and Costello
syndrome-are important to recognize as these are associated with a cancer
predisposition. CBL syndrome carries a very high risk for JMML, thus accurate
diagnosis is of utmost importance. The diagnosis of CBL syndrome in this patient
would not have been possible based on clinical features alone. Through WES, a
specific genetic diagnosis was made, allowing for an optimized management and
surveillance plan, illustrating the power of genomics in clinical practice.
PMID- 28414189
TI - Radioiodinated hypericin disulfonic acid sodium salts as a DNA-binding probe for
early imaging of necrotic myocardium.
AB - Necrotic myocardium imaging can provide great indicators of salvaged myocardial
areas for clinical guidances to patients with myocardial infarction (MI). One of
the key challenges in necrotic myocardium imaging however, is lack of ideal
necrotic imaging tracers for exactly and timely depicting the necrotic
myocardium. 131I-hypericin (131I-Hyp) is a promising tracer in exact necrotic
myocardium delineation. However, it can't clearly image necrotic myocardium until
9h post injection (p.i.) for the high background signals in blood and lung due to
the strong lipophilicity. Herein, an optimized 131I-hypericin-2,5-disulfonic acid
sodium salts (131I-Shyp) probe was synthesized for better pharmacokinetic and
biodistribution properties to necrosis imaging. And the related mechanisms of
necrotic avidity ability of 131I-Hyp and 131I-Shyp were also explored. In the
results, 131I-Shyp still showed selectively high accumulation in both necrotic
cells and tissues. Biodistribution data revealed the decreased uptake of 131I
Shyp in normal organs (lung, spleen and heart) and blood (as shown in
pharmacokinetics studies). 131I-Shyp presented quicker and clearer imaging for
necrotic myocardium at 4h p.i. compared with 131I-Hyp, suggesting that improved
hydrophilicity of 131I-Shyp may be conducive to its better pharmacokinetic and
biodistribution properties to imaging. Additionally, DNA competitive binding
assays and blocking experiments indicated that E-DNA is the possible target of
Shyp and Hyp for their necrosis avidity. 131I-Shyp may serve as a potential E-DNA
targeted probe for necrotic myocardium imaging with molecular specificity for
clinical use.
PMID- 28414186
TI - A review on neuroimaging-based classification studies and associated feature
extraction methods for Alzheimer's disease and its prodromal stages.
AB - Neuroimaging has made it possible to measure pathological brain changes
associated with Alzheimer's disease (AD) in vivo. Over the past decade, these
measures have been increasingly integrated into imaging signatures of AD by means
of classification frameworks, offering promising tools for individualized
diagnosis and prognosis. We reviewed neuroimaging-based studies for AD and mild
cognitive impairment classification, selected after online database searches in
Google Scholar and PubMed (January, 1985-June, 2016). We categorized these
studies based on the following neuroimaging modalities (and sub-categorized based
on features extracted as a post-processing step from these modalities): i)
structural magnetic resonance imaging [MRI] (tissue density, cortical surface,
and hippocampal measurements), ii) functional MRI (functional coherence of
different brain regions, and the strength of the functional connectivity), iii)
diffusion tensor imaging (patterns along the white matter fibers), iv)
fluorodeoxyglucose positron emission tomography (FDG-PET) (metabolic rate of
cerebral glucose), and v) amyloid-PET (amyloid burden). The studies reviewed
indicate that the classification frameworks formulated on the basis of these
features show promise for individualized diagnosis and prediction of clinical
progression. Finally, we provided a detailed account of AD classification
challenges and addressed some future research directions.
PMID- 28414190
TI - Engineered polymeric microspheres obtained by multi-step method as potential
systems for transarterial embolization and intraoperative imaging of HCC:
Preliminary evaluation.
AB - The aim of this study was the development of novel fluorescent microspheres as
embolic agent for transarterial embolization (TAE) of advanced stages of
hepatocellular carcinoma (HCC). TAE is a minimally invasive procedure that
induces tumour regression blocking the blood flow by injection of microparticles.
The microspheres currently used in clinical application cannot be visualized in
vivo. Surgeon could exploit the intraoperative detection of embolic agents during
resection of the malignant mass. Biocompatible indocyanine green (ICG)-loaded
microspheres (CAB-CS-ICG) were prepared using a multi-step method. Chitosan (CS)
ICG particles were prepared via spray-dryer and then loaded into cellulose
acetate butyrate (CAB) microspheres, fabricated by emulsion solvent extraction
method. Technological parameters such as yield, size, encapsulation efficiency
and morphology were studied. CAB-CS-ICG microspheres showed spherical shape and
smooth surface, as well as good injectability through a 21 G*11/2 needle. ICG
release from CAB-CS-ICG was very low due to the strong interaction between CS and
ICG. This result was also confirmed by in vitro fluorescence imaging studies,
conducted using Photodynamic Eye (PDE) for the detection of particles incubated
in human plasma. CAB-CS-ICG were capable to maintain the fluorescence selectivity
for 4weeks. Our data suggested the potential usefulness of CAB-CS-ICG in TAE
application as embolic agents and following imaging of tumour during surgical
procedure.
PMID- 28414191
TI - Instant ODFs - Development of an intermediate, nanoparticle-based product
platform for individualized medication.
AB - The individualization of solid dosage forms to realize a flexible therapy for all
patient groups is a topic which increasingly gains importance in pharmaceutical
research. The goal of this study was to develop a nanoparticulate, instant
orodispersible film (iODF) powder which can easily be reconstituted in water to
cast ODFs containing an individualized concentration of an active pharmaceutical
ingredient (API). It was shown that the processing of the film casing mass to
iODF powders by spray drying provides the same advantageous film properties,
particles sizes redispersed from the ODF and dissolution profiles as compared to
the common production route. Due to the realization of nanoparticle loads up to
50wt.% in the iODF powders, high API loads (11.8mgcm-2) are achieved in final
ODFs. The powders are well storable at different temperatures for at least three
months and do not change their crystalline state during storage. Furthermore,
dissolution of a defined amount of API from ODFs was found to be the fastest with
the highest drug loads in the films.
PMID- 28414192
TI - Congenital erythroderma should be considered as an urgent warning sign of
immunodeficiency: a case of Omenn syndrome.
PMID- 28414193
TI - Generalized lichen nitidus-like eruption in the setting of mogamulizumab and
tremelimumab.
PMID- 28414194
TI - Maculopapular rash during a nadir period in a patient with acute myeloid
leukaemia.
PMID- 28414195
TI - Tegafur/gimeracil/oteracil (TS-1)-induced erythroderma with an extensive mucosal
involvement and hand-foot syndrome.
PMID- 28414196
TI - A cream based on Aquaphilus dolomiae extracts alleviates non-histaminergic
pruritus in humans.
PMID- 28414197
TI - Engineering of a self-adjuvanted iTEP-delivered CTL vaccine.
AB - Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in
cancer and infectious disease therapy. We previously generated an immune-tolerant
elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine
and enhance the efficiency of the vaccine. To further optimize the vaccine
carrier, we intended to potentiate its function by designing an iTEP-based
carrier that was able to deliver adjuvant and a vaccine epitope as one molecule.
Thus, we fused a 9-mer H100, a peptide derived from the high-mobility group box 1
protein (HMGB1) that could induce activation of dendritic cells (DCs), with an
iTEP polymer to generate a new iTEP polymer named H100-iTEP. The H100-iTEP still
kept the feature of reversible phase transition of iTEPs and should be able to be
used as a polymer carrier to deliver peptide vaccines. The expression levels of
CD80/CD86 on DCs were assessed using flow cytometry. The iTEP fusion-stimulated
IL-6 secretion by DCs was measured with ELISA. Activation of antigen-specific
CD8+ T cells induced by iTEP fusions was examined through a B3Z hybridoma cell
activation assay. In vivo CTL activation promoted by iTEP fusions was detected by
an IFN-gamma-based ELISPOT assay. The iTEP fused with H100 could induce
maturation of DCs in vitro as evidenced by increased CD80 and CD86 expression.
The iTEP fusion also promoted activation of DCs by increasing secretion of a
proinflammatory cytokine IL-6. The N-terminus or C-terminus fusion of H100 to
iTEP had a similar effect and a reduced form of cysteine in iTEP fusions was
required for DC stimulation. iTEP fusions potentiated a co-administrated CTL
vaccine by increasing an antigen-specific CTL response in vitro and in vivo. When
the H100-iTEP was fused to a CTL epitope to generate a one-molecule vaccine, this
self-adjuvanted vaccine elicited a stronger antigen-specific CTL response than a
vaccine adjuvanted by Incomplete Freund's Adjuvant. Thus, we have successfully
generated a functional, one-molecule iTEP-based self-adjuvanted vaccine.
PMID- 28414198
TI - LY333531, a PKCbeta inhibitor, attenuates glomerular endothelial cell apoptosis
in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1.
AB - Glomerular endothelial cell (GEC) injury plays an important role in the early
stage of diabetic nephropathy (DN). Previous studies show that a PKCbeta
inhibitor is effective for treating DN. In the current study we further explored
the effects and molecular mechanisms of PKCbeta inhibitors on GEC apoptosis in DN
in streptozotocin-induced diabetic mice in vivo and high glucose- or PMA-treated
human renal glomerular endothelial cells (HRGECs) in vitro. In the diabetic mice,
hyperglycemia caused aggravated nephropathy and GEC apoptosis accompanied by
significantly increased expression of swiprosin-1, a potentally pro-apoptotic
protein. Administration of LY333531 (1 mg.kg-1.d-1 for 8 weeks) significantly
attenuated both GEC apoptosis and swiprosin-1 upregulation in the diabetic mice.
Similar results were observed in high glucose- or PMA-treated HRGECs in vitro.
The pro-apoptotic role of swiprosin-1 was further examined using HRGECs treated
with lentivirus mediating RNA interference or over-expression and swiprosin-1
knockout mice. Over-expression of swiprosin-1 in HRGECs resulted in increases in
apoptosis and in caspase-9, caspase-3 and Bax expression. In contrast, knockdown
of swiprosin-1 attenuated high glucose- or PMA-induced HRGECs apoptosis.
Furthermore, over-expression of swiprosin-1 promoted interaction between
swiprosin-1 and caspase-9 and increased the formation of apoptosomes. In diabetic
swiprosin-1-/- mice, the kidney/body weight, urinary albumin, glomerular
hypertrophy, mitochondrial apoptotic-associated proteins and GEC apoptosis were
significantly attenuated as compared with those in diabetic swiprosin-1+/+ mice.
These results demonstrate that swiprosin-1 is up-regulated by PKCbeta in the
early stage of DN, and that PKCbeta facilitates GEC apoptosis through the
mitochondrial-dependent pathway.
PMID- 28414199
TI - Structure of the PRC2 complex and application to drug discovery.
AB - The polycomb repressive complexes 2 (PRC2) complex catalyzes tri-methylation of
histone H3 lysine 27 (H3K27), a repressive chromatin marker associated with gene
silencing. Overexpression and mutations of PRC2 are found in a wide variety of
cancers, making the catalytic activity of PRC2 an important target of cancer
therapy. This review highlights recent structural breakthroughs of the human PRC2
complex bound to the H3K27 peptide and a small molecule inhibitor, which provide
critically needed insight into PRC2-targeted drug discovery.
PMID- 28414200
TI - Combining 53BP1 with BRCA1 as a biomarker to predict the sensitivity of poly(ADP
ribose) polymerase (PARP) inhibitors.
AB - Over half of patients with BRCA1-deficient cancers do not respond to treatment
with poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we report that
a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor
sensitivity. Based on the mRNA levels of four homologous recombination repair
(HR) genes and PARP inhibitor sensitivity, we selected BRCA1-deficient MDA-MB-436
cells to conduct RNA interference. Reducing expression of 53BP1, but not the
other three HR genes, was found to lower simmiparib sensitivity. Additionally, we
generated 53BP1-/-/BRCA1-/- clonal variants by the transcription activator-like
effector nuclease (TALEN) technique and found that depleting 53BP1 impaired PARP
inhibitor sensitivity with a 36.7-fold increase in their IC50 values. Consistent
with its effect on PARP inhibitor sensitivity, 53BP1 loss alleviated cell cycle
arrest and apoptosis and partially restored HR function. Importantly, 53BP1
depletion dramatically reduced the ability of PARP inhibitors to suppress tumor
growth in vivo. The inhibition rate of simmiparib was 74.16% for BRCA1-deficient
MDA-MB-436 xenografts, but only 7.79% for 53BP1/BRCA1-deficient xenografts. Re
expressing 53BP1 in the dual-deficient cells restored PARP inhibitor sensitivity
and the levels of HR regulators. Considering that at least 10% of BRCA1-deficient
breast and ovarian cancers have reduced expression of 53BP1, using a combination
of 53BP1 with BRCA1 as a biomarker for patient selection should reduce the number
of patients undergoing futile treatment with PARP inhibitors.
PMID- 28414201
TI - Intrinsic radiolabeling of Titanium-45 using mesoporous silica nanoparticles.
AB - Titanium-45 (45Ti) with a three-hour half-life (t1/2=3.08 h), low maximum
positron energy and high positron emission branching ratio, is a suitable
positron emission tomography (PET) isotope whose potential has not yet been fully
explored. Complicated radiochemistry and rapid hydrolysis continue to be major
challenges to the development of 45Ti compounds based on a traditional chelator
based radiolabeling strategy. In this study we introduced an intrinsic (or
chelator-free) radiolabeling technique for the successful labeling of 45Ti using
mesoporous silica nanoparticle (MSN). We synthesized uniform MSN with an average
particle size of ~150 nm in diameter. The intrinsic 45Ti-labeling was
accomplished through strong interactions between 45Ti (hard Lewis acid) and hard
oxygen donors (hard Lewis bases), the deprotonated silanol groups (-Si-O-) from
the outer surface and inner meso-channels of MSN. In vivo tumor-targeted PET
imaging of as-developed PEGylated [45Ti]MSN was further demonstrated in the 4T1
murine breast tumor-bearing mice. This MSN-based intrinsic radiolabeling strategy
could open up new possibilities and speed up the biomedical applications of 45Ti
in the future.
PMID- 28414202
TI - Recent advances in peptide nucleic acid for cancer bionanotechnology.
AB - Peptide nucleic acid (PNA) is an oligomer, in which the phosphate backbone has
been replaced by a pseudopeptide backbone that is meant to mimic DNA. Peptide
nucleic acids are of the utmost importance in the biomedical field because of
their ability to hybridize with neutral nucleic acids and their special chemical
and biological properties. In recent years, PNAs have emerged in
nanobiotechnology for cancer diagnosis and therapy due to their high affinity and
sequence selectivity toward corresponding DNA and RNA. In this review, we
summarize the recent progresses that have been made in cancer detection and
therapy with PNA biotechnology. In addition, we emphasize nanoparticle PNA-based
strategies for the efficient delivery of drugs in anticancer therapies.
PMID- 28414204
TI - Docking-based structural splicing and reassembly strategy to develop novel
deazapurine derivatives as potent B-RafV600E inhibitors.
AB - The mutation of B-RafV600E is widespread in a variety of human cancers. Its
inhibitors vemurafenib and dabrafenib have been launched as drugs for treating
unresectable melanoma, demonstrating that B-RafV600E is an ideal drug target.
This study focused on developing novel B-RafV600E inhibitors as drug leads
against various cancers with B-RafV600E mutation. Using molecular modeling
approaches, 200 blockbuster drugs were spliced to generate 283 fragments followed
by molecular docking to identify potent fragments. Molecular structures of
potential inhibitors of B-RafV600E were then obtained by fragment reassembly
followed by docking to predict the bioactivity of the reassembled molecules. The
structures with high predicted bioactivity were synthesized, followed by in vitro
study to identify potent B-RafV600E inhibitors. A highly potent fragment binding
to the hinge area of B-RafV600E was identified via a docking-based structural
splicing approach. Using the fragment, 14 novel structures were designed by
structural reassembly, two of which were predicted to be as strong as marketed B
RafV600E inhibitors. Biological evaluation revealed that compound 1m is a potent
B-RafV600E inhibitor with an IC50 value of 0.05 MUmol/L, which was lower than
that of vemurafenib (0.13 MUmol/L). Moreover, the selectivity of 1m against B
RafWT was enhanced compared with vemurafenib. In addition, 1m exhibits desirable
solubility, bioavailability and metabolic stability in in vitro assays. Thus, a
highly potent and selective B-RafV600E inhibitor was designed via a docking-based
structural splicing and reassembly strategy and was validated by medicinal
synthesis and biological evaluation.
PMID- 28414203
TI - Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin
for efficient tumor-targeted chemotherapy.
AB - Since the discovery that nano-scaled particulates can easily be incorporated into
tumors via the enhanced permeability and retention (EPR) effect, such
nanostructures have been exploited as therapeutic small molecule delivery
systems. However, the convoluted synthetic process of conventional nanostructures
has impeded their feasibility and reproducibility in clinical applications.
Herein, we report an easily prepared formulation of self-assembled nanostructures
for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic
acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride).
pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong
interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three
nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of
1:1, 2:1, and 4:1, respectively, to investigate the function of the residual PBA
moiety as a targeting ligand. An acid-labile drug release profile was observed,
owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor
targeting ability of the nanocomplexes was demonstrated, both in vitro by
confocal microscopy and in vivo by fluorescence imaging, to be driven by an
inherent property of the residual PBA. Ligand competition assays with free PBA
pre-treatment demonstrated the targeting effect of the residual PBA from the
nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free
DOX, exhibited significantly greater anti-cancer effects in vitro and even in
vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled
nanostructures with potential biomedical applications.
PMID- 28414205
TI - Molecular tumor targeting of gelonin by fusion with F3 peptide.
AB - Therapeutically potent macromolecular drugs have shown great promise for
overcoming the limitations of small-molecule anti-cancer drugs. But tumor cell
selective intracellular delivery of the macromolecules remains a major hurdle for
their successful clinical application. To overcome this challenge, we engineered
a novel genetic fusion protein (F3-Gel) that composed of F3 peptide, a tumor
homing peptide, and gelonin, a plant-derived ribosome-inactivating protein (RIP),
and then evaluated its anti-cancer activity in vitro and in vivo. The F3-Gel
encoding gene was synthesized by genetic recombination, and F3-Gel was
successfully expressed in E coli. The anti-cancer activity of the produced F3-Gel
was evaluated by various in vitro assays, which revealed that F3-Gel maintained
equipotent protein synthesis inhibition activity (IC50=11 pmol/L) as unmodified
gelonin (IC50=10 pmol/L). Furthermore, F3-Gel displayed enhanced cellular uptake
into cancer cells (U87 MG, HeLa, LnCaP and 9L) than noncancerous cells (293 HEK
and SVGp12). Compared with gelonin, F3-Gel exerted significantly higher
cytotoxicity against these cancer cells. F3-Gel displayed significantly greater
inhibition of protein translation in U87 MG cells: F3-Gel (0.5 MUmol/L) was able
to reduce the protein level to less than 50%, while gelonin (1 MUmol/L) did not
affect the intracellular protein level. In a U87 MG xenograft tumor-bearing mouse
model, F3-Gel was accumulated in the tumor site at much higher levels and
maintained for a prolonged time compared with gelonin. Administration of F3-Gel
(0.5, 0.75 mol/kg, iv) caused 36% and 66%, respectively, inhibition of tumor
growth in U87 MG xenograft mice, suggesting that it is a promising candidate drug
for cancer treatment. Furthermore, this study demonstrates that fusion of F3
peptide to a potent macromolecule could provides an effective method for
targeting tumors and eventually could improve their druggability.
PMID- 28414206
TI - Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in
a mouse Xenograft model.
AB - Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an
adjuvant for the prevention of bone metastases in breast cancer patients. In this
study we investigated the efficacy of WSZG in preventing bone metastases and the
potential mechanisms in a mouse xenograft model of breast cancer bone metastases.
This model was established by injection of human MDA-MB-231BO-Luc breast cancer
cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal
stem cells (BMSCs) into left ventricle of the heart in female nude mice. Then the
mice were treated with WSZG (3.25, 6.5 or 13.0 mg.kg-1.d-1, ig) for four weeks,
whereas zoledronic acid (100 MUg/kg per week, ig) was used as a positive control.
The occurrence and development of bone metastases were monitored via
bioluminescent imaging, and bone lesions were assessed using micro-CT.
Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells
with BMSCs significantly facilitated the bone metastatic capacity of the breast
cancer cells, and aggravated bone lesions in the mouse xenograft model of breast
cancer bone metastases. Administration of WSZG dose-dependently inhibited the
incidence and intensity of bone metastases and protected against bone lesions by
suppressing osteoclast formation and tumor cell infiltration. Furthermore,
administration of WSZG caused a marked reduction in the expression of CCL5/CCR5
and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate that WSZG
exerts potential therapeutic effects in a mouse xenograft model of breast cancer
bone metastases, which are partially mediated by weakening the interaction
between BMSCs and breast cancer cells in the tumor microenvironment.
PMID- 28414208
TI - Highly Compressible Nitrogen-Doped Carbon Foam Electrode with Excellent Rate
Capability via a Smart Etching and Catalytic Process.
AB - Freestanding three-dimensional nitrogen-doped carbon foam with large pores is
proposed as a promising electrode configuration for elastic electronics. Although
it exhibits excellent mechanical performance, the capacitive performances
(especially its rate capability) are still unsatisfactory. By using KMnO4, we
demonstrate a smart etching and catalytic process to form highly graphitized and
etched nitrogen-doped carbon foam (ENCF) with an exfoliated carbon-shell
architecture. These compositional and structural features endow the ENCF
electrodes with excellent electron conductivity as well as more ion-accessible
electrochemical active sites. Significantly, all-solid-state symmetric
supercapacitor devices based on the ENCF electrodes exhibit enhanced specific
capacitance and marked high-rate capability. Furthermore, the integrated device
has no significant capacity loss under 60% compressive strain.
PMID- 28414209
TI - Polypharmacological in Silico Bioactivity Profiling and Experimental Validation
Uncovers Sedative-Hypnotic Effects of Approved and Experimental Drugs in Rat.
AB - In this work, we describe the computational ("in silico") mode-of-action analysis
of CNS-active drugs, which is taking both multiple simultaneous hypotheses as
well as sets of protein targets for each mode-of-action into account, and which
was followed by successful prospective in vitro and in vivo validation. Using
sleep-related phenotypic readouts describing both efficacy and side effects for
491 compounds tested in rat, we defined an "optimal" (desirable) sleeping
pattern. Compounds were subjected to in silico target prediction (which was
experimentally confirmed for 21 out of 28 cases), followed by the utilization of
decision trees for deriving polypharmacological bioactivity profiles. We
demonstrated that predicted bioactivities improved classification performance
compared to using only structural information. Moreover, DrugBank molecules were
processed via the same pipeline, and compounds in many cases not annotated as
sedative-hypnotic (alcaftadine, benzatropine, palonosetron, ecopipam,
cyproheptadine, sertindole, and clopenthixol) were prospectively validated in
vivo. Alcaftadine, ecopipam cyproheptadine, and clopenthixol were found to
promote sleep as predicted, benzatropine showed only a small increase in NREM
sleep, whereas sertindole promoted wakefulness. To our knowledge, the sedative
hypnotic effects of alcaftadine and ecopipam have not been previously discussed
in the literature. The method described extends previous single-target, single
mode-of-action models and is applicable across disease areas.
PMID- 28414207
TI - Defining the minimum substrate and charge recognition model of gamma-secretase.
AB - gamma-Secretase is an intramembrane aspartyl protease that cleaves the C99
fragment of amyloid precursor protein to generate extracellular Abeta peptides.
These peptides can oligomerize and aggregate to form amyloid plaques, processes
that are widely believed to be causal for Alzheimer's disease. In spite of this
critical function, it remains unknown how gamma-secretase recognizes C99 and its
other substrates, including Notch. In this study we determined E22-K55 as the
minimal C99 fragment that was sufficient and required for initial cleavage.
Within this fragment, we identified four determinants: (i) a transferable
extracellular determinant that differed between C99 and Notch, and which included
negative charge in the case of C99, (ii) the amino acid sequence of the C
terminal half of the transmembrane helix, (iii) an invariant lysine or arginine
at the intracellular membrane border, and (iv) a positive charge cluster that
included the invariant lysine/arginine. We demonstrated that the charge clusters
of C99 and Notch receptors could directly bind phosphatidylinositol 4,5
bisphosphate (PIP2). The PIP2-binding cluster was required for gamma-secretase
cleavage, and modulation of membrane PIP2 levels strongly affected gamma
secretase cleavage levels and the Abeta40/Abeta42 ratio, providing support for
the importance of the PIP2 interaction in cells. Together, these studies provide
critically needed insight into substrate recognition by gamma-secretase.
PMID- 28414210
TI - Scalable Production of the Silicon-Tin Yin-Yang Hybrid Structure with Graphene
Coating for High Performance Lithium-Ion Battery Anodes.
AB - Alloy anodes possessed of high theoretical capacity show great potential for next
generation advanced lithium-ion battery. Even though huge volume change during
lithium insertion and extraction leads to severe problems, such as pulverization
and an unstable solid-electrolyte interphase (SEI), various nanostructures
including nanoparticles, nanowires, and porous networks can address related
challenges to improve electrochemical performance. However, the complex and
expensive fabrication process hinders the widespread application of
nanostructured alloy anodes, which generate an urgent demand of low-cost and
scalable processes to fabricate building blocks with fine controls of size,
morphology, and porosity. Here, we demonstrate a scalable and low-cost process to
produce a porous yin-yang hybrid composite anode with graphene coating through
high energy ball-milling and selective chemical etching. With void space to
buffer the expansion, the produced functional electrodes demonstrate stable
cycling performance of 910 mAh g-1 over 600 cycles at a rate of 0.5C for Si
graphene "yin" particles and 750 mAh g-1 over 300 cycles at 0.2C for Sn-graphene
"yang" particles. Therefore, we open up a new approach to fabricate alloy anode
materials at low-cost, low-energy consumption, and large scale. This type of
porous silicon or tin composite with graphene coating can also potentially play a
significant role in thermoelectrics and optoelectronics applications.
PMID- 28414211
TI - Correction to Enhancing Efficiency and Stability of Perovskite Solar Cells
through Nb-Doping of TiO2 at Low Temperature.
PMID- 28414212
TI - Development of 3D Urchin-Shaped Coaxial Manganese Dioxide@Polyaniline (MnO2@PANI)
Composite and Self-Assembled 3D Pillared Graphene Foam for Asymmetric All-Solid
State Flexible Supercapacitor Application.
AB - We have fabricated high-energy-density all-solid-state flexible asymmetric
supercapacitor by using a facile novel 3D hollow urchin-shaped coaxial manganese
dioxide@polyaniline (MnO2@PANI) composite as positive electrode and 3D graphene
foam (GF) as negative electrode materials with polyvinyl alcohol (PVA)/KOH gel
electrolyte. The coaxial MnO2@PANI composite was fabricated by hydrothermal route
followed by oxidation without use of an external oxidant. The formation mechanism
of the 3D hollow MnO2@PANI composite occurs first by nucleation and growth of the
MnO2 crystal species via dissolution-recrystallization and oriented attachment
mechanisms followed by the oxidation of aniline monomers on the MnO2 crystalline
template. The self-assembled 3D graphene block was synthesized by hydrothermal
route using vitamin C as a reducing agent. The microstructures of the composites
are analyzed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS),
and Raman spectroscopy. The morphology is characterized by field-emission
scanning electron microscopy (FESEM) and transmission electron microscopy (TEM),
which clearly showed the formation of urchin-shaped coaxial MnO2@PANI composite.
The electrochemical studies are explored by cyclic voltammetry, electrochemical
impedance spectrometry, and cyclic charge-discharge tests. The symmetric all
solid-state flexible MnO2@PANI//MnO2@PANI and GF//GF supercapacitors exhibit the
specific capacitance of 129.2 and 82.1 F g-1 at 0.5 A/g current density,
respectively. The solid-state asymmetric supercapacitor shows higher energy
density (37 Wh kg-1) with respect to the solid-state symmetric supercapacitors
MnO2@PANI//MnO2@PANI and GF//GF, where the obtained energy density are found to
be 17.9 and 11.4 Wh kg-1, respectively, at 0.5 A/g current density. Surprisingly,
the asymmetric supercapacitor shows a high energy density of 22.3 Wh kg-1 at a
high current density of 5 A g-1. The solid-state asymmetric supercapacitor shows
a good cyclic stability in which ~11% capacitance loss was observed after 5000
cycles.
PMID- 28414213
TI - Immobilization and Stabilization of Acylase on Carboxylated Polyaniline
Nanofibers for Highly Effective Antifouling Application via Quorum Quenching.
AB - Acylase (AC) was immobilized and stabilized on carboxylated polyaniline
nanofibers (cPANFs) for the development of antifouling nanobiocatalysts with high
enzyme loading and stability. AC was immobilized via three different approaches:
covalent attachment (CA), enzyme coating (EC), and magnetically separable enzyme
precipitate coating (Mag-EPC). The enzyme activity per unit weight of cPANFs with
Mag-EPC was 75 and 300 times higher than that of those with CA and EC,
respectively, representing improved enzyme loading in the form of Mag-EPC. After
incubation under shaking at 200 rpm for 20 days, Mag-EPC maintained 55% of its
initial activity, whereas CA and EC showed 3 and 16% of their initial activities,
respectively. The antifouling of highly loaded and stable Mag-EPC against the
biofouling/biofilm formation of Pseudomonas aeruginosa was tested under static-
and continuous-flow conditions. Biofilm formation in the presence of 40 MUg/mL
Mag-EPC under static condition was 5 times lower than that under control
condition with no addition of Mag-EPC. Under continuous membrane filtration, Mag
EPC delayed the increase of transmembrane pressure (TMP) more effectively as the
concentration of added Mag-EPC increased. When separating Mag-EPC and membranes
in two different vessels under internal circulation of the culture solution, Mag
EPC maintained a higher permeability than the control with no Mag-EPC addition.
It was also confirmed that the addition of Mag-EPC reduced the generation of N
acyl homoserine lactone (AHL) autoinducers. This result reveals that the
inhibition of biofilm formation and biofouling in the presence of Mag-EPC is due
to the hydrolysis of AHL autoinducers, catalyzed by the immobilized and
stabilized AC in the form of Mag-EPC. Mag-EPC of AC with high enzyme loadings and
improved stability has demonstrated its great potential as an antifouling agent
by reducing biofilm formation and membrane biofouling based on "enzymatic quorum
quenching" of autoinducers.
PMID- 28414214
TI - Reconfigurable Complementary Monolayer MoTe2 Field-Effect Transistors for
Integrated Circuits.
AB - Transition metal dichalcogenides are of interest for next generation switches,
but the lack of low resistance electron and hole contacts in the same material
has hindered the development of complementary field-effect transistors and
circuits. We demonstrate an air-stable, reconfigurable, complementary monolayer
MoTe2 field-effect transistor encapsulated in hexagonal boron nitride, using
electrostatically doped contacts. The introduction of a multigate design with
prepatterned bottom contacts allows us to independently achieve low contact
resistance and threshold voltage tuning, while also decoupling the Schottky
contacts and channel gating. We illustrate a complementary inverter and a p-i-n
diode as potential applications.
PMID- 28414215
TI - Highly Sensitive Naked-Eye Assay for Enterovirus 71 Detection Based on Catalytic
Nanoparticle Aggregation and Immunomagnetic Amplification.
AB - Development of sensitive, convenient, and cost-effective virus detection product
is of great significance to meet the growing demand of clinical diagnosis at the
early stage of virus infection. Herein, a naked-eye readout of immunoassay by
means of virion bridged catalase-mediated in situ reduction of gold ions and
growth of nanoparticles, has been successfully proposed for rapid visual
detection of Enterovirus 71 (EV71). Through tailoring the morphologies of the
produced gold nanoparticles (GNPs) varying between dispersion and aggregation, a
distinguishing color changing was ready for observation. This colorimetric
detection assay, by further orchestrating the efficient magnetic enrichment and
the high catalytic activity of enzyme, is managed to realize highly sensitive
detection of EV71 virions with the limit of detection (LOD) down to 0.65 ng/mL.
Our proposed method showed a much lower LOD value than the commercial ELISA for
EV71 virion detection. Comparing to the current clinical gold standard polymerase
chain reaction (PCR) method, our strategy provided the same diagnostic outcomes
after testing real clinical samples. Besides, this strategy has no need of
complicated sample pretreatment or expensive instruments. Our presented naked-eye
immunoassay method holds a promising prospect for the early detection of virus
infectious disease especially in resource-constrained settings.
PMID- 28414217
TI - Selection of Group-Specific Phthalic Acid Esters Binding DNA Aptamers via
Rationally Designed Target Immobilization and Applications for Ultrasensitive and
Highly Selective Detection of Phthalic Acid Esters.
AB - Phthalic acid esters (PAEs) are ubiquitous in the environment, and some of them
are recognized as endocrine disruptors that cause concerns on ecosystem
functioning and public health. Due to the diversity of PAEs in the environment,
there is a vital need to detect the total concentration of PAEs in a timely and
low-cost way. To fulfill this requirement, it is highly desired to obtain group
specific PAE binders that are specific to the basic PAE skeleton. In this study,
for the first time we have identified the group-specific PAE-binding aptamers via
rationally designed target immobilization. The two target immobilization
strategies were adopted to display either the phthalic ester group or the alkyl
chain, respectively, at the surface of the immobilization matrix. The former
enabled the rapid enrichment of aptamers after four rounds of selection. The top
100 sequences are cytosine-rich (44.7%) and differentiate from each other by only
1-4 nucleotides at limited locations. The top two aptamers all display the
nanomolar dissociation constants to both the immobilized target and the free PAEs
[dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis(2-ethylhexyl)
phthalate (DEHP)]. We further demonstrate the applications of the aptamers in the
development of high-throughput PAE assays and DEHP electrochemical biosensors
with exceptional sensitivity [limit of detection (LOD), 10 pM] and selectivity
(>105-fold). PAE aptamers targeting one of the most sought for targets thus offer
the promise of convenient, low-cost detection of total PAEs. Our study also
provides insights on the aptamer selection and sensor development of highly
hydrophobic small molecules.
PMID- 28414218
TI - Exploiting the Anti-Aggregation of Gold Nanostars for Rapid Detection of Hand,
Foot, and Mouth Disease Causing Enterovirus 71 Using Surface-Enhanced Raman
Spectroscopy.
AB - Enterovirus 71 (EV71) is a major public health threat that requires rapid point
of-care detection. Here, we developed a surface-enhanced Raman spectroscopy
(SERS)-based scheme that utilized protein-induced aggregation of colloidal gold
nanostars (AuNS) to rapidly detect EV71 without the need for fabricating a solid
substrate, Raman labels or complicated sample handling. We used AuNS
(hydrodynamic diameter, DH of 105.12 +/- 1.13 nm) conjugated to recombinant
scavenger receptor class B, member 2 (SCARB2) protein with known affinity to
EV71. In the absence of EV71, AuNS-SCARB2 aggregated in biological media and
produced four enhanced Raman peaks at 390, 510, 670, and 910 cm-1. In the
presence of EV71, the three peaks at 510, 670, and 910 cm-1 disappeared, while
the peak at 390 cm-1 diminished in intensity as the virus bound to AuNS-SCARB2
and prevented them from aggregation. These three peaks (510, 670, and 910 cm-1)
were potential markers for specific detection of EV71 as their disappearance was
not observable with a different dengue virus (DENV) as our control. Furthermore,
the Raman measurements from colloidal SERS were more sensitive in probing the
aggregation of AuNS-SCARB2 for detecting the presence of EV71 in protein-rich
samples compared to UV-vis spectrum measurements. With this facile "anti
aggregation" approach, we were able to detect EV71 in protein-rich biological
medium within 15 min with reasonable sensitivity of 107 pfu/mL and minimal sample
preparation, making this translatable for point-of-care applications.
PMID- 28414219
TI - Anion Encapsulation Drives the Formation of Dimeric GdIII[15-metallacrown-5]3+
Complexes in Aqueous Solution.
AB - Metallacrown complexes capable of sequestering dianions, as shown in the solid
state, also exist in aqueous solution at neutral pH, as demonstrated by
calorimetric and mass spectrometric data. The driving forces for the formation of
these dimeric complexes in solution strongly depend on the chain length of the
guest rather than its degree of unsaturation.
PMID- 28414220
TI - Alkane-Shape-Selective Vapochromic Behavior Based on Crystal-State Host-Guest
Complexation of Pillar[5]arene Containing One Benzoquinone Unit.
AB - Colored crystals of pillar[5]arene containing one benzoquinone unit were found to
exhibit alkane-shape-selective vapochromic behavior. Activated pillar[5]arene
crystals, prepared by removing solvated methanol from pillar[5]arene crystals,
changed color from dark-brown to light-red after exposure to linear alkane
vapors; however, no color changes were observed on exposure to branched or cyclic
alkanes. Uptake of methanol vapor by the activated crystals induced a different
color change, from dark-brown to black. This multi-vapochromism results from the
different intermolecular pi-stacking interactions between the benzoquinone and
1,4-diethoxybenzene units in the alkane- and methanol-containing crystals. Unlike
most known vapochromic materials, these pillar[5]arene-based materials were
highly stable; after uptake of n-alkanes or methanol the color of the crystals
did not change after storage in air for 3 weeks. This is because the included
guests were stabilized in the cavity by multiple CH/pi interactions.
PMID- 28414216
TI - Unraveling the Thousand Word Picture: An Introduction to Super-Resolution Data
Analysis.
AB - Super-resolution microscopy provides direct insight into fundamental biological
processes occurring at length scales smaller than light's diffraction limit. The
analysis of data at such scales has brought statistical and machine learning
methods into the mainstream. Here we provide a survey of data analysis methods
starting from an overview of basic statistical techniques underlying the analysis
of super-resolution and, more broadly, imaging data. We subsequently break down
the analysis of super-resolution data into four problems: the localization
problem, the counting problem, the linking problem, and what we've termed the
interpretation problem.
PMID- 28414221
TI - New Isolated-Pentagon-Rule Isomers of Fullerene C98 Captured as Chloro
Derivatives.
AB - Fullerene C98 possesses 259 isomers obeying the isolated pentagon rule (IPR),
from which two, nos. 116 and 248, have been confirmed earlier as chloro
derivatives. High-temperature chlorination of C98-containing mixtures afforded
crystals of several chloro derivatives, and their structure elucidation by X-ray
crystallography revealed the presence of new isomers, nos. 107, 109, and 120, in
the fullerene soot. Evidence for an isomer of no. 111 is also presented. In
addition, a new chloride of the known isomer 248 has been isolated and
structurally studied. The chlorination patterns of the chlorides are discussed in
terms of the formation of isolated C?C bonds and aromatic substructures on the
fullerene cages.
PMID- 28414222
TI - Supramolecular Photoactivatable Anticancer Hydrogels.
AB - A photoactivatable dopamine-conjugated platinum(IV) anticancer complex (Pt-DA)
has been incorporated into G-quadruplex G4K+ borate hydrogels by using borate
ester linkages (Pt-G4K+B hydrogel). These were characterized by 11B NMR,
attenuated total reflection Fourier transform infrared spectroscopy, circular
dichroism, scanning electron microscopy and transmission electron microscopy.
Microscopy investigations revealed the transformation of an extended fiber
assembly into discrete flakes after incorporation of Pt-DA. Pt-DA showed
photocytotoxicity against cisplatin-resistant A2780Cis human ovarian cancer cells
(IC50 74 MUM, blue light) with a photocytotoxic index <2, whereas Pt-G4K+B
hydrogels exhibited more potent photocytotoxicity (IC50 3 MUM, blue light) with a
photocytotoxic index >5. Most notably, Pt-DA and Pt-G4K+B hydrogels show
selective phototoxicity for cancer cells versus normal fibroblast cells (MRC5).
PMID- 28414224
TI - Carbanion Translocations via Intramolecular Proton Transfers: A Quantum Chemical
Study.
AB - Intramolecular proton transfers are important processes in chemical reactions and
biological transformations. In particular, the translocation of reactive
carbanion centers can be achieved through 1,n-proton transfer in either a direct
or an assisted manner (via the protonation/deprotonation mechanism). Despite some
mechanistic investigations on proton transfers within zwitterionic species, no
guiding principles have been summarized for carbanion-induced intramolecular
proton transfers. Herein, we report our quantum chemical study on the carbanion
translocations via intramolecular proton transfers. Our calculations indicated
that the reaction barriers generally decrease with longer tether lengths and more
pi-withdrawing substituents. The physical bases behind these effects were
revealed according to the charge and bond energy decomposition analysis, showing
that the destabilizing closed-shell Pauli repulsions play important roles in
determining the relative ease of intramolecular proton transfers. We also found
that the thermodynamic driving force may affect the regiochemistry. This study
may help chemists to understand whether a carbanion translocation occurs via an
intramolecular proton transfer or with the assistance of proton shuttles, such as
water and alcohols.
PMID- 28414223
TI - Diversity-Oriented Stapling Yields Intrinsically Cell-Penetrant Inducers of
Autophagy.
AB - Autophagy is an essential pathway by which cellular and foreign material are
degraded and recycled in eukaryotic cells. Induction of autophagy is a promising
approach for treating diverse human diseases, including neurodegenerative
disorders and infectious diseases. Here, we report the use of a diversity
oriented stapling approach to produce autophagy-inducing peptides that are
intrinsically cell-penetrant. These peptides induce autophagy at micromolar
concentrations in vitro, have aggregate-clearing activity in a cellular model of
Huntington's disease, and induce autophagy in vivo. Unexpectedly, the solution
structure of the most potent stapled peptide, DD5-o, revealed an alpha-helical
conformation in methanol, stabilized by an unusual (i,i+3) staple which cross
links two d-amino acids. We also developed a novel assay for cell penetration
that reports exclusively on cytosolic access and used it to quantitatively
compare the cell penetration of DD5-o and other autophagy-inducing peptides.
These new, cell-penetrant autophagy inducers and their molecular details are
critical advances in the effort to understand and control autophagy. More
broadly, diversity-oriented stapling may provide a promising alternative to
polycationic sequences as a means for rendering peptides more cell-penetrant.
PMID- 28414225
TI - Reversible Gas-Solid Ammonia N-H Bond Activation Mediated by an Organopalladium
Complex.
AB - N-H bond activation of gaseous ammonia is achieved at room temperature in a
reversible solvent-free reaction using a solid dicyclopalladated azobenzene
complex. Monitoring of the gas-solid reaction in real-time by in situ solid-state
Raman spectroscopy enabled a detailed insight into the stepwise activation
pathway proceeding to the final amido complex via a stable diammine intermediate.
Gas-solid synthesis allowed for isolation and subsequent structural
characterization of the intermediate and the final amido product, which presents
the first dipalladated complex with the PdII-(MU-NH2)-PdII bridge. Gas-solid
reaction is readily followed via color changes associated with conformational
switching of the palladated azobenzene backbone. The reaction proceeds
analogously in solution and was characterized by UV-vis and NMR spectroscopies
showing the same stepwise route to the amido complex. Combining the experimental
data with density functional theory calculations we propose a stepwise mechanism
of this heterolytic N-H bond activation assisted by exogenous ammonia.
PMID- 28414227
TI - Quantifying the Role of Orbital Contraction in Chemical Bonding.
AB - This work reports an approach to variationally quantify orbital contraction in
chemical bonds by an extension of an energy decomposition analysis (EDA). The
orbital contraction energy is defined as the energy lowering due to optimization
of the isolated fragments (that combine to form the bond) with a specially
constructed virtual set of contraction/expansion functions. This set contains one
function per occupied orbital, obtained as the linear response to scaling the
nuclear charges. EDA results for a variety of single bonds show substantial
changes in the importance of orbital contraction; it plays a critical role for
bonds to H but only a very minor role in the bonds between heavier elements.
Additionally, energetic stabilization due to rehybridization is separated from
inductive polarization by the fact that no mixing with virtual orbitals is
involved and is shown to be significant in fragments such as NH2, OH, and F.
PMID- 28414226
TI - Testing the Push-Pull Hypothesis: Lewis Acid Augmented N2 Activation at Iron.
AB - We present a systematic investigation of the structural and electronic changes
that occur in an Fe(0)-N2 unit (Fe(depe)2(N2); depe = 1,2
bis(diethylphosphino)ethane) upon the addition of exogenous Lewis acids. Addition
of neutral boranes, alkali metal cations, and an Fe2+ complex increases the N-N
bond activation (Delta nuNN up to 172 cm-1), decreases the Fe(0)-N2 redox
potential, polarizes the N-N bond, and enables -N protonation at uncommonly
anodic potentials. These effects were rationalized using combined experimental
and theoretical studies.
PMID- 28414228
TI - Molecular Aspects of a Robust Assay for Ferroxidase Function of Ceruloplasmin.
AB - Ceruloplasmin (Cp) is one of the most complex multicopper oxidase enzymes and
plays an essential role in the metabolism of iron in mammals. Ferrous ion
supplied by the ferroportin exporter is converted by Cp to ferric ion that is
accepted by plasma metallo-chaperone transferrin. Study of the enzyme at the
atomic and molecular level has been hampered by the lack of a suitable ferrous
substrate. We have developed the classic chromophoric complex FeIIHx(Tar)2
(H2Tar, 4-(2-thiazolylazo)resorcinol; x = 0-2; overall charge omitted) as a
robust substrate for evaluation of the ferroxidase function of Cp and related
enzymes. The catalysis can be followed conveniently in real time by monitoring
the solution absorbance at 720 nm, a fingerprint of FeIIHx(Tar)2. The complex is
oxidized to its ferric form FeIIIHx(Tar)2 via the overall reaction sequence
FeIIHx(Tar)2 -> FeII-Cp -> FeIII-Cp -> FeIIIHx(Tar)2: i.e., Fe(II) is transferred
formally from FeIIHx(Tar)2 to the substrate docking/oxidation (SDO) site(s) in
Cp, followed by oxidation to product Fe(III) that is trapped again by the ligand.
Each Tar ligand in the above bis-complex coordinates the metal center in a
meridional tridentate mode involving a pH-sensitive -OH group (pKa > 12), and
this imposes rapid Fe(II) and Fe(III) transfer kinetics to facilitate the
catalytic process. The formation constants of both the ferrous and ferric
complexes at pH 7.0 were determined (log beta2' = 13.6 and 21.6, respectively),
as well as an average dissociation constant of the SDO site(s) in Cp (log KD' =
7.2).
PMID- 28414229
TI - Coding the Assembly of Polyoxotungstates with a Programmable Reaction System.
AB - Chemical transformations are normally conducted in batch or flow mode, thereby
allowing the chemistry to be temporally or spatially controlled, but these
approaches are not normally combined dynamically. However, the investigation of
the underlying chemistry masked by the self-assembly processes that often occur
in one-pot reactions and exploitation of the potential of complex chemical
systems requires control in both time and space. Additionally, maintaining the
intermediate constituents of a self-assembled system "off equilibrium" and
utilizing them dynamically at specific time intervals provide access to building
blocks that cannot coexist under one-pot conditions and ultimately to the
formation of new clusters. Herein, we implement the concept of a programmable
networked reaction system, allowing us to connect discrete "one-pot" reactions
that produce the building block{W11O38} = {W11} under different conditions and
control, in real time, the assembly of a series of polyoxometalate clusters
{W12O42} = {W12}, {W22O74} = {W22} 1a, {W34O116} = {W34} 2a, and {W36O120} =
{W36} 3a, using pH and ultraviolet-visible monitoring. The programmable networked
reaction system reveals that is possible to assemble a range of different
clusters using {W11}-based building blocks, demonstrating the relationship
between the clusters within the family of iso-polyoxotungstates, with the final
structural motif being entirely dependent on the building block libraries
generated in each separate reaction space within the network. In total, this
approach led to the isolation of five distinct inorganic clusters using a "fixed"
set of reagents and using a fully automated sequence code, rather than five
entirely different reaction protocols. As such, this approach allows us to
discover, record, and implement complex one-pot reaction syntheses in a more
general way, increasing the yield and reproducibility and potentially giving
access to nonspecialists.
PMID- 28414230
TI - Computer-Aided 13C NMR Chemical Profiling of Crude Natural Extracts without
Fractionation.
AB - A computer-aided, 13C NMR-based dereplication method is presented for the
chemical profiling of natural extracts without any fractionation. An algorithm
was developed in order to compare the 13C NMR chemical shifts obtained from a
single routine spectrum with a set of predicted NMR data stored in a natural
metabolite database. The algorithm evaluates the quality of the matching between
experimental and predicted data by calculating a score function and returns the
list of metabolites that are most likely to be present in the studied extract.
The proof of principle of the method is demonstrated on a crude alkaloid extract
obtained from the leaves of Peumus boldus, resulting in the identification of
eight alkaloids, including isocorydine, rogersine, boldine, reticuline,
coclaurine, laurotetanine, N-methylcoclaurine, and norisocorydine, as well as
three monoterpenes, namely, p-cymene, eucalyptol, and alpha-terpinene. The
results were compared to those obtained with other methods, either involving a
fractionation step before the chemical profiling process or using mass
spectrometry detection in the infusion mode or coupled to gas chromatography.
PMID- 28414231
TI - Organic Phosphorescence Nanowire Lasers.
AB - Organic solid-state lasers (OSSLs) based on singlet fluorescence have merited
intensive study as an important class of light sources. Although the use of
triplet phosphors has led to 100% internal quantum efficiency in organic light
emitting diodes (OLEDs), stumbling blocks in triplet lasing include generally
forbidden intersystem crossing (ISC) and a low quantum yield of phosphorescence
(PhiP). Here, we reported the first triplet-phosphorescence OSSL from a nanowire
microcavity of a sulfide-substituted difluoroboron compound. As compared with the
unsubstituted parent compound, the lone pair of electrons of sulfur substitution
plus the intramolecular charge transfer interaction introduced by the nitro
moiety lead to an highly efficient T1 (pi,pi*) <- S1 (n,pi*) ISC (PhiISC = 100%)
and a moderate PhiP (10%). This, plus the optical feedback provided by nanowire
Fabry-Perot microcavity, enables triplet-phosphorescence OSSL emission at 650 nm
under pulsed excitation. Our results open the door for a whole new class of laser
materials based on previously untapped triplet phosphors.
PMID- 28414232
TI - Application of Deep Eutectic Solvents (DES) for Phenolic Compounds Extraction:
Overview, Challenges, and Opportunities.
AB - The green chemistry era has pushed the scientific community to investigate and
implement new solvents in phenolic compounds (PC) extraction as alternatives to
organic solvents, which are toxic and may be dangerous. Recently, deep eutectic
solvents (DES) have been applied as extraction solvents for PC. They have the
advantages of biodegradability and ease of handling with very low toxicity.
Nevertheless, the extraction process is affected by several factors: affinity
between DES and the target compounds, the water content, the mole ratio between
DES' starting molecules, the liquid/solid ratio between the DES and sample, and
the conditions and extraction method. On the other hand, PC recovery from DES is
a challenge because they can establish a strong hydrogen bond network.
Alternatively, another possibility is to use DES as solvent extraction as well as
formulation medium. In this way, DES can be suitable for cosmetics,
pharmaceutical, or food applications.
PMID- 28414233
TI - Furfural: The Unimolecular Dissociative Photoionization Mechanism of the Simplest
Furanic Aldehyde.
AB - The unimolecular dissociation reactions of energy-selected furfural cations have
been studied by imaging photoelectron photoion coincidence spectroscopy at the
vacuum-ultraviolet (VUV) beamline of the Swiss Light Source. In the photon energy
range of 10.9-14.5 eV, furfural ions decay by numerous fragmentation channels.
Modeling the breakdown diagram yielded the 0 K appearance energies of 10.95 +/-
0.10, 11.16, and 12.03 eV for the c-C4H3O-CO+ (m/z = 95), c-C4H4O+ (m/z = 68),
and c-C3H3+ (m/z = 39) fragment ions, respectively, formed by parallel
dissociation channels. An internal conversion from the A" to the A' electronic
state via a conical intersection takes place along the reaction coordinate in the
case of the H-loss channel (c-C4H3O-CO+ formation). Quantum chemical calculations
and experimental results confirmed a fast conversion to the A' state and that the
rate-determining step is a tight transition state on the potential energy
surface. Appearance energies were also derived for the sequential dissociation
products from the furan cation, c-C4H4O+, for the formation of CH2CO+ (m/z = 42),
C3H4+ (m/z = 40), and CHO+ (m/z = 29) at 12.81, 12.80, and 13.34 eV,
respectively. Statistical rate theory modeling of the breakdown diagram can also
be used to predict the fractional ion abundances and thermal shifts in mass
spectrometric pyrolysis studies to help assigning the m/z channels either to
ionization of the neutrals or to dissociative ionization processes, with
potential use for combustion diagnostics. The cationic geometry optimizations
yielded functional-dependent spurious DFT minima and a deviating planar MP2
optimized geometry, which are briefly discussed.
PMID- 28414234
TI - Impact of Mutations at C-Terminus on Structures and Dynamics of Abeta40 and
Abeta42: A Molecular Simulation Study.
AB - Alzheimer's disease is presumed to be caused by the formation of intracellular
plaques of amyloid beta (Abeta) peptides inside neurons. The most abundant Abeta
forms are Abeta40 and Abeta42 comprising, respectively, 40 and 42 residues.
Recent experiments showed that the triple Gly33Val-Val36Pro-Gly38Val (VPV)
mutation causes Abeta42 to become "super-Abeta42" with elevated aggregation rates
and toxicity. Upon VPV mutation, oligomerization pathways of Abeta40 become
similar to those of the Abeta42 wild type. It was hypothesized that the super
behavior of Abeta42 occurs due to an enhanced content of the beta-turn and beta
hairpin, centered at residues 36-37, and the similarity in oligomerization
pathways of Abeta40-VPV and Abeta42-WT comes from the increased beta-turn
population. As this is based on simulation of the truncated fragments, this
hypothesis may not be valid for the full-length case, motivating us to perform
all-atom molecular dynamics simulations for full-length Abeta sequences. We
showed that the results obtained for truncated peptides fall short in explaining
the similarity of self-assembly pathways of Abeta40-VPV and Abeta42-WT. Instead,
we propose that the similarity is due to not only increased beta-turn population
but also due to the elevated beta-structure of the entire sequence. Similar to
VPV, the Gly33Val-Val36Asn-Gly38Leu mutation enhances the beta-structure and the
C-terminal beta-turn making the behavior of Abeta40 similar to that of Abeta42
WT.
PMID- 28414235
TI - Bis-Heteroleptic Ruthenium(II) Complex of Pendant Urea Functionalized Pyridyl
Triazole and Phenathroline for Recognition, Sensing, and Extraction of Oxyanions.
AB - A new bis-heteroleptic RuII complex based ditopic receptor, 1[PF6]2, having an
anion binding triazole -CH unit and appended 4-fluorophenyl urea arm has been
developed. 1H NMR and isothermal titration calorimetry (ITC) experiments showed
binding of 1[PF6]2 toward oxyanions such as phosphates (e.g., H2PO4- and HP2O73-)
and carboxylates (e.g., CH3CO2- and C6H5CO2-) anions selectively. 1H NMR studies
showed that highly basic phosphate anions such as HP2O73-/H2PO4- are bound by
both -CH and -NH units of complex 1[PF6]2. However, comparatively less basic
CH3CO2-, C6H5CO2- anions interacted with the urea -NH protons only. Thermodynamic
parameters obtained from ITC experiments suggested that binding of all the
interacting anions with complex 1[PF6]2 are highly enthalpy and entropy driven
processes. Importantly, complex 1[PF6]2 showed extraction of H2PO4-, CH3CO2-, and
C6H5CO2- anions from aqueous solution via liquid-liquid extraction with
efficiencies of 28%, 74%, and 80%, respectively. The influential role of the urea
moiety in the course of extraction is demonstrated by comparison with a model
complex, 2[PF6]2. Additionally, complex 1[PF6]2 is capable of selective sensing
of phosphate anions among all investigated anions.
PMID- 28414236
TI - Thermal Rearrangement of Sulfamoyl Azides: Reactivity and Mechanistic Study.
AB - The rearrangement of sulfamoyl azides under thermal conditions to form a C-C bond
while breaking two C-N bonds is reported. Mechanistic study shows that this
reaction goes through a Curtius-type rearrangement to form a 1,1-diazene, then
which rearranges possibly through both a concerted rearrangement process and a
stepwise radical process. This rearrangement could be used in the synthesis of
complex biologically active molecules, such as sterols, and piperine derivatives.
PMID- 28414237
TI - CuX-Activated N-Halosuccinimide: Synthesis of 3-Haloquinolines via Electrophilic
Cyclization of Alkynyl Imines.
AB - We report an electrophilic cyclization of alkynyl imines to afford
polysubstituted 3-haloquinolines using CuX-activated N-halosuccinimdes (NXS) as
electrophiles. Control experiments demonstrated that the NXS/CuX system might be
more active than single NXS and could be applied in the electrophilic cyclization
of electron- deficient substrates.
PMID- 28414238
TI - Template Approach to Crystalline GaN Nanosheets.
AB - Crystalline GaN nanosheets hold great challenge in growth and promising
application in optoelectronic nanodevices. In this work, we reported an
accessible template approach toward the rational synthesis of GaN nanosheets
through the nitridation of metastable gamma-Ga2O3 nanosheets synthesized from a
hydrothermal reaction. The cubic gamma-Ga2O3 nanosheets with smooth surface and
decent crystallinity can be directly converted into hexagonal GaN nanosheets with
similar morphology framework and comparable crystal quality in NH3 at 850
degrees C. UV-vis spectrum measurement reveals that the GaN nanosheets show a
band gap of 3.30 eV with strong visible absorption in the range of 370-500 nm.
The template synthetic strategy proposed in this work will open up more
opportunities for the achievement of a variety of sheetlike nanostructures that
can not be obtained through conventional routines and will undoubtedly further
promote the fundamental research of newly emerging sheetlike nanostructures and
nanotechnology.
PMID- 28414239
TI - A Novel Sample Preparation for Shotgun Proteomics Characterization of HCPs in
Antibodies.
AB - Residual host cell proteins (HCPs) in biopharmaceuticals derived from recombinant
DNA technology can present potential safety risks to patients or compromise
product stability. Thus, the downstream purification process is designed to
demonstrate robust removal of these impurities. ELISA using polyclonal anti-HCP
antibodies as reagents for capture, detection, and quantitation purposes is most
commonly used to monitor HCP removal during process development, but this
technique has limitations. More recently, LC-MS for residual HCP characterization
has emerged as a powerful tool to support purification process development.
However, mass spectrometry needs to overcome the enormous dynamic range to detect
low ppm levels of residual HCPs in biopharmaceutical samples. We describe a
simple and powerful methodology to characterize residual HCPs in (monoclonal)
antibodies by combining a novel sample preparation procedure using trypsin
digestion and a shotgun proteomics approach. Differing from the traditional
methodology, the sample preparation approach maintains nearly intact antibody
while HCPs are digested. Thus, the dynamic range for HCP detection by MS is 1 to
2 orders of magnitude less than the traditional trypsin digestion sample
preparation procedure. HCP spiking experiments demonstrated that our method could
detect 0.5 ppm of HCP with molecular weight >60 kDa, such as rPLBL2. Application
of our method to analyze a high-purity NIST monoclonal antibody standard RM 8670
derived from a murine cell line expression system resulted in detection of 60
mouse HCPs; twice as many as previously reported with 2D-UPLC/IM/MSE method. A
control monoclonal antibody used for 70 analyses over 450 days demonstrated that
our method is robust.
PMID- 28414240
TI - Light-Activated COS/H2S Donation from Photocaged Thiocarbamates.
AB - Hydrogen sulfide (H2S) is an important biomolecule, and responsive chemical tools
for its delivery are needed. Here, we utilize the photocleavable o-nitrobenzyl
group to unmask caged thiocarbamates and to access photoactivated H2S releasing
molecules. These donors function by the initial release of carbonyl sulfide
(COS), which is quickly hydrolyzed to H2S by carbonic anhydrase (CA). Our
investigations demonstrate that o-nitrobenzyl-caged thiocarbamates can serve as a
donor platform for the bio-orthogonal stimulated release of COS/H2S.
PMID- 28414241
TI - Hot Electron Transistor with van der Waals Base-Collector Heterojunction and High
Performance GaN Emitter.
AB - Single layer graphene is an ideal material for the base layer of hot electron
transistors (HETs) for potential terahertz (THz) applications. The ultrathin body
and exceptionally long mean free path maximizes the probability for ballistic
transport across the base of the HET. We demonstrate for the first time the
operation of a high-performance HET using a graphene/WSe2 van der Waals (vdW)
heterostructure as a base-collector barrier. The resulting device with a GaN/AlN
heterojunction as emitter, exhibits a current density of 50 A/cm2, direct current
gain above 3 and 75% injection efficiency, which are record values among graphene
base HETs. These results not only provide a scheme to overcome the limitations of
graphene-base HETs toward THz operation but are also the first demonstration of a
GaN/vdW heterostructure in HETs, revealing the potential for novel electronic and
optoelectronic applications.
PMID- 28414242
TI - Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1
yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5
carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical
Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis.
AB - Autotaxin is a circulating enzyme with a major role in the production of
lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has
been suggested in many disease areas including pulmonary fibrosis. Structural
modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG
inhibition, remove CYP3A4 time-dependent inhibition, and improve pharmacokinetic
properties, led to the identification of clinical candidate GLPG1690 (11).
Compound 11 was able to cause a sustained reduction of LPA levels in plasma in
vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis
model in mice and in reducing extracellular matrix deposition in the lung while
also reducing LPA 18:2 content in bronchoalveolar lavage fluid. Compound 11 is
currently being evaluated in an exploratory phase 2a study in idiopathic
pulmonary fibrosis patients.
PMID- 28414244
TI - Morphology Development in Solution-Processed Functional Organic Blend Films: An
In Situ Viewpoint.
AB - Solution-processed organic films are a facile route to high-speed, low cost,
large-area deposition of electrically functional components (transistors, solar
cells, emitters, etc.) that can enable a diversity of emerging technologies, from
Industry 4.0, to the Internet of things, to point-of-use heath care and elder
care. The extreme sensitivity of the functional performance of organic films to
structure and the general nonequilibrium nature of solution drying result in
extreme processing-performance correlations. In this Review, we highlight
insights into the fundamentals of solution-based film deposition afforded by
recent state-of-the-art in situ measurements of functional film drying. Emphasis
is placed on multimodal studies that combine surface-sensitive X-ray scattering
(GIWAXS or GISAXS) with optical characterization to clearly define the evolution
of solute structure (aggregation, crystallinity, and morphology) with film
thickness.
PMID- 28414243
TI - Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic
Asymmetric Hydroboration of Trisubstituted Alkenes.
AB - Highly enantioselective rhodium-catalyzed hydroboration of allylic phosphonates
by pinacolborane affords chiral tertiary boronic esters. The beta-borylated
phosphonates are readily converted to chiral beta- and gamma-hydroxyphosphonates
and aminophosphonates and to phosphonates bearing a quaternary carbon
stereocenter. The utility of the latter is illustrated by the synthesis of (S)
(+)-bakuchiol methyl ether.
PMID- 28414245
TI - Interfacial Properties and Monolayer Collapse of Alkyl Benzenesulfonate
Surfactant Monolayers at the Decane-Water Interface from Molecular Dynamics
Simulations.
AB - The molecular structure of a surfactant molecule is known to have a great effect
on the interfacial properties and the type of nanostructures formed. In this
work, we have performed molecular dynamics simulations on six isomers of an alkyl
benzenesulfonate surfactant to investigate the effect of the degree and position
of aromatic substitution on the interfacial properties and on the collapse of the
surfactant monolayer at a decane-water interface. The surface pressure of the
monolayers was shown to increase with increasing surface coverage, until some of
the monolayers become mechanically unstable and form large undulations. Shifting
the primary alkyl chain of the surfactant from the para to the meta position was
found to significantly affect the orientation of the surfactant head groups,
while the attachment position of the benzene ring along the primary alkyl chain
plays a greater role in the orientation of the surfactant tails. In general, to
the extent considered in this work, our results suggest that additional alkyl
substitution and meta substitution of the primary alkyl chains increase both the
effectiveness and efficiency of the surfactants, and accelerate the onset of
monolayer collapse. The interface was found to consist of an inner Helmholtz
layer of partially dehydrated counterions in contact with the surfactant head
groups, an outer Helmholtz layer of hydrated counterions, and a diffuse layer.
The di- and trisubstituted surfactants formed nearly spherical swollen micelles
encapsulating pure decane, which effectively solubilizes decane in water as a
microemulsion. The monosubstituted surfactants formed elongated buds that
protrude from the interface, but did not detach from the monolayer. To our
knowledge, the role of aromatic substitution on interfacial properties has not
been investigated by molecular simulations previously. The results from this work
could provide insights to design improved surfactants by exploiting aromatic
substitution to encapsulate material for drug delivery and other applications.
PMID- 28414246
TI - Ganoderin A, a novel 9,11-secosterol from Ganoderma lucidum spores oil.
AB - In this study, four sterols were isolated from the Ganoderma lucidum spores oil
obtained via supercritical CO2 extraction. Four chemical constituents were
ganoderin A (1), chaxine B (2), ergosterol, (3) and stellasterol (4). All the
separated ingredients were characterized using spectral data interpretation and
by comparing with reported data. Noticeably, stellasterol and chaxine B were both
firstly isolated from Ganoderma lucidum spores oil and ganoderin A was shown to
bear an unprecedented skeleton.
PMID- 28414247
TI - Preoperative sexual status of Japanese localized prostate cancer patients:
comparison of sexual activity and EPIC scores.
AB - OBJECTIVE: This study aimed to evaluate the relationship between sexual activity
and sexual function using questionnaires distributed to middle-aged Japanese
patients with localized prostate cancer. METHODS: A total of 145 patients who
underwent radical prostatectomy were enrolled in the survey reported on herein.
Sexual activity and sexual function were investigated via the Expanded Prostate
Cancer Index Composite (EPIC) and an original self-reported questionnaire.
RESULTS: Of participants, 24.1% and 20.7% had sexual activity within a month
period as investigated via the EPIC and original questionnaire, respectively.
However, 29.7% of all those who reported sexual activity rate reported "about
once every 2 months to a year," as shown in the original questionnaire. Regarding
sexual function as addressed through EPIC, no results within that questionnaire's
measure of sexual function showed significant differences among patients with a
rate of actual sexual activity. CONCLUSIONS: The present survey showed that more
than quarter of preoperative middle-aged Japanese prostate cancer patients
surveyed had actual sexual activity, though not within the preceding 4 weeks. To
precisely evaluate sexual function of middle-aged Japanese patients, it is
necessary to consider actual sexual activity.
PMID- 28414248
TI - Factors that predict discharge recommendations following paediatric mild
traumatic brain injury.
AB - PRIMARY OBJECTIVE: To investigate factors that predict discharge recommendations
for children and adolescents who present to an Australian paediatric Emergency
Department (ED) following a mild traumatic brain injury (mTBI). RESEARCH DESIGN:
Retrospective data base analysis. METHODS: The study retrospectively analysed an
ED database to test the relationship between injury risk factors (symptoms,
Glasgow Coma Scale, prior TBI, mechanism of injury and Computed Tomography scan),
non-injury risk factors (sex, age, socio-economic status (SES)) and discharge
recommendations of 2807 children and adolescents (0-18 years) who presented to a
children's hospital ED over a three year period with mTBI. RESULTS: Univariate
analyses indicated a statistically significant association of discharge
recommendations with age, SES, mechanism of injury and vomiting. However,
multivariate analyses indicated vomiting and mechanism of injury were the only
statistically significant risk factor associated with discharge recommendations,
when controlling for other risk factors. CONCLUSIONS: The current study suggests
vomiting and mechanism of injury are the only risk factors predicting discharge
recommendations for children and adolescents with mTBI.
PMID- 28414249
TI - Psychological distress is associated with altered cognitive functioning in family
caregivers of patients with disorders of consciousness.
AB - OBJECTIVES: To analyse the possible presence of reduced cognitive efficiency in
family caregivers of patients with prolonged disorders of consciousness (DOC).
SUBJECTS: The participants were 27 caregivers of 25 patients with DOC admitted to
the severe brain injury units of the ICS Maugeri, Institutes of Telese Terme and
Sciacca, Italy. METHODS: We examined cognitive functions such as short- and long
term memory, executive functions and attention by means of standardized tests. We
also assessed features of psychological distress such as anxiety, depression,
psychophysiological symptoms, prolonged grief disorder, psychological burden and
quality of life. All scores on neuropsychological tests were compared with those
of the 15 matched control subjects. RESULTS: Enrolled family caregivers showed
high frequency of clinically relevant depressive symptoms and anxiety; half of
them met the criteria for prolonged grief disorder. Caregivers achieved scores
lower than the matched controls on tests for selective attention, verbal fluency
and long-term spatial memory. CONCLUSIONS: Family caregivers' burden is
associated with a reduced efficiency of selected executive measures and
visuospatial learning. These results emphasize the need for appropriate
psychological and cognitive supporting therapies for family caregivers of
patients with DOC, also considering their delicate involvement in clinical
decision-making and in providing care.
PMID- 28414250
TI - Longitudinal changes in brain morphology from 4 weeks to 12 months after mild
traumatic brain injury: Associations with cognitive functions and clinical
variables.
AB - OBJECTIVE: To investigate longitudinal changes in cortical and subcortical
volumes in patients with mild traumatic brain injury (MTBI) and to evaluate
whether such changes were associated with self-reported post-concussive symptoms,
global functional outcomes and neuropsychological functioning. METHODS: This was
a prospecitve, longitudinal cohort study of patients with complicated (i.e
presence of intracranial abnormalities on the day of injury CT) and uncomplicated
MTBI (i.e, absence of intracranial abnormalities). Magnetic resonance imaging
(MRI) was performed at approximately 4 weeks and 12 months. We utilized a 3T MRI
system, cortical reconstruction and volumetric segmentation by FreeSurfer
software. We included 33 patients with uncomplicated and 29 with complicated
MTBI, who were aged 16-65 years. RESULTS: 12 months after MTBI, significant
within-group volume reductions were detected in the left accumbens area and right
caudate nucleus for both patients groups, but no significant differences between
the groups were revealed. No associations between volumetric variables and post
concussive symptoms or global functioning were found. The left temporal thickness
was significantly associated with executive functioning. CONCLUSION: Structural
subcortical alterations occur after complicated and uncomplicated MTBIs but these
findings were not associated with symptoms burden or functional outcomes.
Nonetheless, worse executive functioning was found in patients with shrinkage of
the left temporal lobe.
PMID- 28414251
TI - Impact of metabolic status on the association of serum vitamin D with
hypogonadism and lower urinary tract symptoms/benign prostatic hyperplasia.
AB - OBJECTIVE: The objective of this study is to investigate the impact of metabolic
status on associations of serum vitamin D with hypogonadism and lower urinary
tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A
total of 612 men underwent physical examination, biochemical/hormonal blood
testing, and transrectal prostate ultrasound. Moreover, the subjects filled out
standard questionnaires for identification and grading of LUTS and hypogonadism
symptoms. Parameters were statistically compared with independent t-tests and
correlation analyses. RESULTS: Vitamin D levels positively correlated with total
testosterone (TT) but not with prostate volume or International Prostate Symptom
Score (IPSS). Patients with metabolic syndrome had significantly lower vitamin D
levels, which were not correlated with TT, prostate volume, or IPSS. However,
vitamin D was positively correlated with TT, and negatively correlated with
prostate volume and quality-of-life IPSS in subjects without metabolic syndrome.
CONCLUSION: The clinical usefulness of vitamin D for treatment of hypogonadism or
LUTS/BPH varies according to metabolic status.
PMID- 28414252
TI - Environmental impacts of genetically modified (GM) crop use 1996-2015: Impacts on
pesticide use and carbon emissions.
AB - This paper updates previous assessments of important environmental impacts
associated with using crop biotechnology in global agriculture. It focuses on the
environmental impacts associated with changes in pesticide use and greenhouse gas
emissions arising from the use of GM crops since their first widespread
commercial use in the mid-1990s. The adoption of GM insect resistant and
herbicide tolerant technology has reduced pesticide spraying by 618.7 million kg
(-8.1%) and, as a result, decreased the environmental impact associated with
herbicide and insecticide use on these crops (as measured by the indicator, the
Environmental Impact Quotient (EIQ)) by18.6%. The technology has also facilitated
important cuts in fuel use and tillage changes, resulting in a significant
reduction in the release of greenhouse gas emissions from the GM cropping area.
In 2015, this was equivalent to removing 11.9 million cars from the roads.
PMID- 28414253
TI - Suggestions for assessment of muscle mass in primary care setting.
AB - Sarcopenia is one of the prevalent geriatric syndromes that adversely affects the
functionality in the older adults. The diagnosis of sarcopenia requires
documentation of decreased muscle mass and decreased muscle strength or physical
function. The implication of user-friendly and inexpensive methods that could be
used to assess sarcopenia in real-life settings is suggested in a recent debate
paper. For muscle mass assessment, bioelectric impedance analysis (BIA), and dual
energy X-ray absorptiometry (DXA) were described as having the same ease for
muscle mass assessment in terms of applicability. However, BIA is easier to
perform, has greater availability, inexpensive, and does not require specialist
trained staff. The authors proposed the use of DXA as primary tool to assess
muscle mass in the primary care setting. However, BIA is recommended as a first
line method both in research and clinical practice by EWGSOP. Regarding its much
easier applicability, we conclude that BIA is a more practical method for muscle
mass assessment in the primary care setting than the DXA. Thus, we suggest that
BIA could be the method of choice for muscle mass assessment in the primary care
setting.
PMID- 28414254
TI - Lifestyle intervention for adults with spinal cord injury: Results of the USC
RLANRC Pressure Ulcer Prevention Study.
AB - CONTEXT/OBJECTIVE: Medically serious pressure injuries (MSPrIs), a common
complication of spinal cord injury (SCI), have devastating consequences on health
and well-being and are extremely expensive to treat. We aimed to test the
efficacy of a lifestyle-based intervention designed to reduce incidence of MSPrIs
in adults with SCI. DESIGN: A randomized controlled trial (RCT), and a separate
study wing involving a nonrandomized standard care control group. SETTING: Rancho
Los Amigos National Rehabilitation Center, a large facility serving ethnically
diverse, low income residents of Los Angeles County. PARTICIPANTS: Adults with
SCI, with history of one or more MSPrIs over the past 5 years: N=166 for RCT
component, N=66 in nonrandomized control group. INTERVENTIONS: The Pressure Ulcer
Prevention Program, a 12-month lifestyle-based treatment administered by
healthcare professionals, largely via in-home visits and phone contacts. OUTCOME
MEASURES: Blinded assessments of annualized MSPrI incidence rates at 12 and 24
months, based on: skin checks, quarterly phone interviews with participants, and
review of medical charts and billing records. Secondary outcomes included number
of surgeries and various quality-of-life measures. RESULTS: Annualized MSPrI
rates did not differ significantly between study groups. At 12 months, rates were
.56 for intervention recipients, .48 for randomized controls, and .65 for
nonrandomized controls. At follow-up, rates were .44 and .39 respectively for
randomized intervention and control participants. CONCLUSIONS: Evidence for
intervention efficacy was inconclusive. The intractable nature of MSPrI threat in
high-risk SCI populations, and lack of statistical power, may have contributed to
this inability to detect an effect. TRIAL REGISTRATION: ClinicalTrials.gov
NCT01999816.
PMID- 28414255
TI - A Quantitative Assessment of the Risk of Human Salmonellosis Arising from the
Consumption of Almonds in the United States: The Impact of Preventive Treatment
Levels.
AB - The presence of Salmonella on almonds continues to result in product-related
outbreaks and recalls in the United States. In this study, the impact of
microbial reduction treatment levels (1 to 5 log CFU) on the risk of human
salmonellosis from the consumption of almond kernels in the United States was
evaluated. An exposure model, including major steps in almond processing, was
used to estimate prevalence and levels of contamination of Salmonella on almonds
at the point of consumption. A Salmonella dose-response model and consumption
data for almonds in the United States were used to assess risk of illness per
serving and per year, quantifying variability and uncertainty separately. A 3-log
reduction treatment resulted in a predicted mean risk of illness of two cases per
year for almonds consumed as a core product not cooked at home (95% confidence
interval [CI], one to four cases), one case per year for almonds consumed as an
ingredient not cooked at home (95% CI, one to two cases), and less than one case
per year for almonds consumed as an ingredient cooked at home (95% CI, 7 * 10-7
to 3 * 10-6 cases). A minimum 4-log reduction treatment resulted in an estimated
mean risk of illness below one case per year in the United States. This study
also includes an assessment of the risk of human salmonellosis as a result of an
exceptional situation, which results in higher risk estimates compared with the
baseline model. The exceptional situations modeled posttreatment resulted in
estimates of mean risk that were not significantly affected by treatment level.
Sensitivity analysis results showed initial Salmonella contamination level to be
the factor with the most impact on risk per serving estimates, given a certain
treatment level. The risk assessment also includes a simulation of the events
that occurred in 2001. Treatment levels with a minimum 4-log microbial reduction
would have been sufficient to prevent the outbreak cases. The uncertainty range
in the estimates indicates that additional information is needed to make more
precise predictions of this specific outbreak event.
PMID- 28414256
TI - Salmonella Survival Kinetics on Pecans, Hazelnuts, and Pine Nuts at Various Water
Activities and Temperatures.
AB - The impact of temperature, water activity (aw), and nut composition on Salmonella
survival on tree nuts has not been thoroughly examined. The aim of this study was
to determine the effect of temperature, aw, and nut composition on the survival
of Salmonella on tree nuts and develop predictive models. Pecans, hazelnuts, and
pine nuts were chosen based on differences in their typical fat content. Nuts
were inoculated with a cocktail of five Salmonella serotypes (11 log CFU/mL) and
then were dried and stored at 4, 10, and 25 degrees C at 0.41 +/- 0.06 and 0.60
+/- 0.05 aw for 1 year. Ten-gram quantities were removed at different intervals
up to 364 days to test for surviving Salmonella populations (plating on selective
and nonselective media) and aw. Experiments were carried out in triplicate.
Salmonella populations were relatively stable over a year at 4 and 10 degrees C
at both aw levels with <1.5-log CFU/g decline. The best predictive model to
describe Salmonella survival at 4 and 10 degrees C was a log-linear model with a
D-value for each tree nut and aw combination. Significant declines in Salmonella
levels were observed at 25 degrees C, where the best fit was a Weibull model with
a fixed rho for all tree nuts (rho = 0.86), a delta value for each tree nut and
aw combination, and a random factor to account for variability among replicates.
The time for the first log reduction at 25 degrees C and 0.37 +/- 0.009 aw was
estimated at 24 +/- 2 weeks for hazelnuts, 34 +/- 3 weeks for pecans, and 52 +/-
7 weeks for pine nuts. At the same temperature, but with 0.54 +/- 0.009 aw, the
mean estimated time for the first log reduction decreased to 9 +/- 1 weeks for
hazelnuts, 10 +/- 1 weeks for pecans, and 16 +/- 1 weeks for pine nuts. Tree nut,
aw, and temperature were shown to have a statistically significant effect on
survival ( P < 0.05). No apparent influence of fat content on survival was
observed. The results of this study can be used to predict changes in Salmonella
levels on pecans, hazelnuts, and pine nuts after storage at the different
temperatures and aw values.
PMID- 28414257
TI - Spiral Plating Method To Quantify the Six Major Non-O157 Escherichia coli
Serogroups in Cattle Feces.
AB - Cattle are a major reservoir of the six major Shiga toxin-producing non-O157
Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, and O145)
responsible for foodborne illnesses in humans. Besides prevalence in feces, the
concentrations of STEC in cattle feces play a major role in their transmission
dynamics. A subset of cattle, referred to as super shedders, shed E. coli O157 at
high concentrations (>=4 log CFU/g of feces). It is not known whether a similar
pattern of fecal shedding exists for non-O157. Our objectives were to initially
validate the spiral plating method to quantify the six non-O157 E. coli
serogroups with pure cultures and culture-spiked fecal samples and then determine
the applicability of the method and compare it with multiplex quantitative PCR
(mqPCR) assays for the quantification of the six non-O157 E. coli serogroups in
cattle fecal samples collected from commercial feedlots. Quantification limits of
the spiral plating method were 3 log, 3 to 4 log, and 3 to 5 log CFU/mL or CFU/g
for individual cultures, pooled pure cultures, and cattle fecal samples spiked
with pooled pure cultures, respectively. Of the 1,152 cattle fecal samples tested
from eight commercial feedlots, 122 (10.6%) and 320 (27.8%) harbored
concentrations >=4 log CFU/g of one or more of the six serogroups of non-O157 by
spiral plating and mqPCR methods, respectively. A majority of quantifiable
samples, detected by either spiral plating (135 of 137, 98.5%) or mqPCR (239 of
320, 74.7%), were shedding only one serogroup. Only one of the quantifiable
samples was positive for a serogroup carrying Shiga toxin (stx1) and intimin
(eae) genes; 38 samples were positive for serogroups carrying the intimin gene.
In conclusion, the spiral plating method can be used to quantify non-O157
serogroups in cattle feces, and our study identified a subset of cattle that was
super shedders of non-O157 E. coli . The method has the advantage of quantifying
non-O157 STEC, unlike mqPCR that quantifies serogroups only.
PMID- 28414258
TI - Postchill Antimicrobial Treatments To Control Salmonella, Listeria, and
Campylobacter Contamination on Chicken Skin Used in Ground Chicken.
AB - Ground poultry products are frequently contaminated with foodborne pathogens.
With the potential for increased regulatory scrutiny, it is important to use
sufficient intervention strategies to control pathogen levels effectively. A
large proportion of the bacteria introduced to ground chicken are likely to come
from broiler skin, which is added to achieve target fat content and maintain
product texture and taste. In this research, antimicrobials, including 50 ppm of
chlorine and 1,200 ppm of peracetic acid (PAA), were applied in a postchill
system to reduce the number of Salmonella Typhimurium, Listeria monocytogenes ,
and Campylobacter coli inoculated on chicken skin used to formulate ground
chicken. Results showed that chlorine provided no significant effect in reducing
the number of pathogens in ground chicken made with treated skin compared with
water treatment but that it did help decrease pathogens in postchill water. PAA
was found to be an effective (P <= 0.05) antimicrobial agent, not only in
reducing the number of pathogens on ground chicken, but also in postchill water.
Treating chicken skin with PAA prior to inclusion in ground chicken can be an
effective intervention strategy to lessen contamination in a ground chicken meat
product.
PMID- 28414259
TI - Mixed-effects location and scale Tobit joint models for heterogeneous
longitudinal data with skewness, detection limits, and measurement errors.
AB - The joint modeling of mean and variance for longitudinal data is an active
research area. This type of model has the advantage of accounting for
heteroscedasticity commonly observed in between and within subject variations.
Most of researches focus on improving the estimating efficiency but ignore many
data features frequently encountered in practice. In this article, we develop a
mixed-effects location scale joint model that concurrently accounts for
longitudinal data with multiple features. Specifically, our joint model handles
heterogeneity, skewness, limit of detection, measurement errors in covariates
which are typically observed in the collection of longitudinal data from many
studies. We employ a Bayesian approach for making inference on the joint model.
The proposed model and method are applied to an AIDS study. Simulation studies
are performed to assess the performance of the proposed method. Alternative
models under different conditions are compared.
PMID- 28414260
TI - Retention in HIV Care and Viral Suppression: Individual- and Neighborhood-Level
Predictors of Racial/Ethnic Differences, Florida, 2015.
AB - The objective of this study was to estimate racial/ethnic differences in
retention in HIV care and viral suppression and to identify related individual
and neighborhood determinants. Florida HIV surveillance records of cases aged
>=13 years diagnosed during the years 2000-2014 were analyzed. Retention in care
was defined as evidence of >=2 or more laboratory tests, receipts of
prescription, or clinical visits at least 3 months apart during 2015. Viral load
suppression was defined as a viral load of <200 copies/mL for the last test in
2015. Multi-level logistic regressions were used to estimate adjusted odds ratios
(AORs). Of 65,735 cases, 33.3% were not retained in care, and 40.1% were not
virally suppressed. After controlling for individual and neighborhood factors,
blacks were at increased odds of nonretention in HIV care [AOR 1.29, 95%
confidence interval (CI) 1.23-1.35] and nonviral suppression (AOR 1.55, 95% CI
1.48-1.63) compared with whites. Black and Latino males compared with their
female counterparts had higher odds of nonretention and nonviral suppression.
Compared with their US-born counterparts, foreign-born blacks and whites, but not
Latinos, had higher odds of nonretention and nonviral suppression. Blacks and
whites in urban compared with rural areas had higher odds of both outcomes.
Disparities in retention in care and viral suppression persist and are not
accounted for by differences in age, sex, transmission mode, AIDS diagnosis,
neighborhood socioeconomic status, rural/urban residence, or neighborhood racial
composition. Further, predictors of poor retention in care and viral suppression
appear to differ by race/ethnicity.
PMID- 28414261
TI - "Support Your Client at the Space That They're in": HIV Pre-Exposure Prophylaxis
(PrEP) Prescribers' Perspectives on PrEP-Related Risk Compensation.
AB - Despite the demonstrated effectiveness of HIV pre-exposure prophylaxis (PrEP) and
evidence that most PrEP users do not engage in risk compensation (i.e., increased
risk behavior due to a perceived decrease in HIV susceptibility), some healthcare
providers report patient risk compensation to be a deterrent to prescribing PrEP.
Overcoming this barrier is essential to supporting PrEP access and uptake among
people at risk for HIV. To inform such efforts, this qualitative study explored
PrEP-related risk compensation attitudes among providers with firsthand
experience prescribing PrEP. US-based PrEP providers (n = 18), most of whom were
HIV specialists, were recruited through direct outreach and referral from
colleagues and other participants. Individual 90-min semistructured interviews
were conducted by phone or in person from September 2014 through February 2015,
transcribed, and thematically analyzed. Three attitudinal themes emerged: (1)
providers' role is to support patients in making informed decisions, (2) risk
behavior while taking PrEP does not fully offset PrEP's protective benefit (i.e.,
PrEP confers net protection, even with added behavioral risk), and (3) PrEP
related risk compensation is unduly stigmatized within and beyond the healthcare
community. Participants were critical of other healthcare providers' negative
judgment of patients and reluctance to prescribe PrEP due to anticipated risk
compensation. Several providers also acknowledged an evolution in their thinking
from initial ambivalence toward greater acceptance of PrEP and PrEP-related
behavior change. PrEP providers' insights about risk compensation may help to
address unsubstantiated concerns about PrEP-related risk compensation and
challenge the acceptability of withholding PrEP on these grounds.
PMID- 28414262
TI - Mitey Costly: Energetic Costs of Parasite Avoidance and Infection.
AB - Parasites reduce host fitness via perturbations to host energy allocation,
growth, survival, and reproduction. Here, we investigate the independent effects
of parasite exposure and infection on host metabolic rate. Our study focuses on
Drosophila hydei and a naturally occurring ectoparasitic mite, Macrocheles
muscaedomesticae. We use flow-through respirometry to measure the metabolic rate
of flies during the period of exposure (preinfection) and during mite attachment.
Flies were exposed to mites either indirectly (through a mesh screen) or
directly, allowing for physical contact between the fly and the mite. We
predicted that fly metabolic rate would increase with the level of parasite
exposure: unexposed flies < flies with indirect exposure to mites < flies with
direct contact with mites < flies actively infected with mites. As expected,
flies indirectly exposed to but not in direct contact with mites produced 70%
more CO2 than unexposed flies. Flies in direct contact with mites produced 35%
more CO2 than flies with indirect contact, and this was more than double the
amount of CO2 produced by unexposed flies. However, infected flies-those actually
carrying mites-did not produce significantly more CO2 than uninfected flies. Our
results show that simply being exposed to mites, either indirectly or directly,
was sufficient to elicit a response from the host in terms of elevated CO2
production. Our results show that the costs of parasitism can potentially extend
beyond the physiological costs of infection per se to include the energetic costs
associated with parasite avoidance. Although studies have shown energetic costs
associate with predator-avoidance behaviors, no study to our knowledge has
measured the metabolic cost of parasite avoidance.
PMID- 28414263
TI - Effective enhancement of polylactic acid-degrading enzyme production by
Amycolatopsis sp. strain SCM_MK2-4 using statistical and one-factor-at-a-time
approaches.
AB - This study aims to find the optimal medium and conditions for polylactic acid
(PLA)-degrading enzyme production by Amycolatopsis sp. SCM_MK2-4. Screening of
the most effective components in the enzyme production medium by Plackett-Burman
design revealed that the silk cocoon and PLA film were the most significant
variables enhancing the PLA-degrading enzyme production. After an response
surface methodology, a maximum amount of PLA-degrading enzyme activity at 0.74 U
mL-1 was predicted and successfully validated at 95% after 0.39% (w/v) silk
cocoon and 1.62% (w/v) PLA film were applied to the basal medium. The optimal
initial pH value, temperature, and inoculum size were evaluated by a method
considering one-factor-at-a-time. The values were recorded at an initial pH in
the range of 7.5-9.0, a temperature of 30-32 degrees C, and an inoculum size of 4
10%. The highest activity of approximately 0.95 U mL-1 was achieved after 4 days
of cultivation using the optimized medium and under optimized conditions in a
shake flask. Upscaling to the use of a 3-L stirred tank fermenter was found to be
successful with a PLA-degrading activity of 5.53 U mL-1; which represents a 51
fold increase in the activity compared with that obtained from the nonoptimized
medium and conditions in the shake flask.
PMID- 28414264
TI - The rice transcription factors OsICE confer enhanced cold tolerance in transgenic
Arabidopsis.
AB - Cold stress is one of the major constraints for crop yield. Plants have in turn
evolved highly sophisticated mechanisms involving altered physiologic and
biochemical processes to cope with the cold stress. Previous studies have
revealed that the INDUCER OF CBF EXPRESSION 1 (ICE1), a basic helix-loop-helix
(bHLH) transcription factor, directly binds and activates the expression of C
Repeat Binding Factor/Dehydration-Responsive-Element-Binding protein (CBF/DREB1)
to regulate the cold-response pathway in Arabidopsis thaliana. However, the
function of AtICE1 orthologues in rice is largely unknown. Here we identified
that OsICE1 and OsICE2 in rice shared highly conserved amino acid sequence with
AtICE1 in Arabidopsis. Overexpression of OsICE1 and OsICE2 in Arabidopsis
significantly enhanced the cold tolerance of Arabidopsis seedlings and improved
the expression of cold-response genes. Furthermore, we showed that both OsICE1
and OsICE2 physically interact with OsMYBS3, a single DNA-binding repeat MYB
transcription factor that is essential for cold adaptation in rice, suggesting
that OsICE1/OsICE2 and OsMYBS3 probably act through specific signal transduction
mechanisms to coordinate cold tolerance in rice. These results demonstrated that
the 2 OsICEs are orthologues of AtICE1 and play positive regulators in activation
of cold-response genes to regulate the cold tolerance.
PMID- 28414265
TI - Effectiveness of a Home-Based Eccentric-Exercise Program on the Torque-Angle
Relationship of the Shoulder External Rotators: A Pilot Study.
AB - CONTEXT: The role of the rotator cuff is to provide dynamic stability to the
glenohumeral joint. Human and animal studies have identified sarcomerogenesis as
an outcome of eccentric training indicated by more torque generation with the
muscle in a lengthened position. OBJECTIVE: The authors hypothesized that a home
based eccentric-exercise program could increase the shoulder external rotators'
eccentric strength at terminal internal rotation (IR). DESIGN: Prospective case
series. SETTING: Clinical laboratory and home exercising. PARTICIPANTS: 10
healthy subjects (age 30 +/- 10 y). INTERVENTION: All participants performed 2
eccentric exercises targeting the posterior shoulder for 6 wk using a home-based
intervention program using side-lying external rotation (ER) and horizontal
abduction. MAIN OUTCOME MEASURES: Dynamic eccentric shoulder strength measured at
60 degrees /s through a 100 degrees arc divided into 4 equal 25 degrees arcs
(ER 50-25 degrees , ER 25-0 degrees , IR 0-25 degrees , IR 25-50 degrees ) to
measure angular impulse to represent the work performed. In addition, isometric
shoulder ER was measured at 5 points throughout the arc of motion (45 degrees
IR, 30 degrees IR, 15 degrees IR, 0 degrees , and 15 degrees ER). Comparison
of isometric and dynamic strength from pre- to posttesting was evaluated with a
repeated-measure ANOVA using time and arc or positions as within factors.
RESULTS: The isometric force measures revealed no significant differences between
the 5 positions (P = .56). Analysis of the dynamic eccentric data revealed a
significant difference between arcs (P = .02). The percentage-change score of the
arc of IR 25-50 degrees was found to be significantly greater than that of the
arc of IR 0-25 degrees (P = .007). CONCLUSION: After eccentric training the only
arc of motion that had a positive improvement in the capacity to absorb eccentric
loads was the arc of motion that represented eccentric contractions at the
longest muscle length.
PMID- 28414266
TI - Eccentric Contractions: They Are Not So "Odd" Anymore.
PMID- 28414267
TI - Withdrawal: Rigby and Draper (2017).
AB - We, the Authors, Editors and Publishers of Journal of Sport Rehabilitation, have
withdrawn the following article in whole:Rigby, JH, Draper, DO. Effects of long
duration low intensity ultrasound for active trapezius trigger points: a
randomized clinical trial [version of record published online ahead of print
February 9, 2017]. J Sport Rehabil. doi: 10.1123/jsr.2016-0150.The Editorial
Office was contacted by the author with the request to withdraw this article,
while informing the Editor-in-Chief that the manufacturer of a device used in
this study had contacted the author to disclose that the data reported in the
manuscript had possibly been affected by the failure of the device.
PMID- 28414268
TI - Shifting the Current Clinical Perspective: Isolated Eccentric Exercise as an
Effective Intervention to Promote the Recovery of Muscle After Injury.
AB - Eccentric exercise is able to mechanically engage muscle, initiating strain
sensing molecules that promote muscle recovery by inducing beneficial adaptations
in neural activity and muscle morphology, 2 critical components of muscle
function that are negatively altered after injury. However, due to misinterpreted
mathematic modeling and in situ and in vitro stretch protocols, a dogma that
exposing muscle to eccentric exercise is associated with injury has been
perpetuated in the literature. In response, clinicians have been biased toward
using concentric exercise postinjury to improve the recovery of muscle function.
Unfortunately, this conventional approach to rehabilitation does not restore
muscle function, and reinjury rates remain high. Here, the authors present
experimental evidence and theoretical support for the idea that isolated
eccentric exercise is ideally suited to combat muscle inhibition and muscle
strains and is an attractive alternative to concentric exercise.
PMID- 28414269
TI - Continuous transport of a small fraction of plasma membrane cholesterol to
endoplasmic reticulum regulates total cellular cholesterol.
AB - Cells employ regulated transport mechanisms to ensure that their plasma membranes
(PMs) are optimally supplied with cholesterol derived from uptake of low-density
lipoproteins (LDL) and synthesis. To date, all inhibitors of cholesterol
transport block steps in lysosomes, limiting our understanding of post-lysosomal
transport steps. Here, we establish the cholesterol-binding domain 4 of
anthrolysin O (ALOD4) as a reversible inhibitor of cholesterol transport from PM
to endoplasmic reticulum (ER). Using ALOD4, we: (1) deplete ER cholesterol
without altering PM or overall cellular cholesterol levels; (2) demonstrate that
LDL-derived cholesterol travels from lysosomes first to PM to meet cholesterol
needs, and subsequently from PM to regulatory domains of ER to suppress
activation of SREBPs, halting cholesterol uptake and synthesis; and (3) determine
that continuous PM-to-ER cholesterol transport allows ER to constantly monitor PM
cholesterol levels, and respond rapidly to small declines in cellular cholesterol
by activating SREBPs, increasing cholesterol uptake and synthesis.
PMID- 28414271
TI - Monitoring ATP dynamics in electrically active white matter tracts.
AB - In several neurodegenerative diseases and myelin disorders, the degeneration
profiles of myelinated axons are compatible with underlying energy deficits.
However, it is presently impossible to measure selectively axonal ATP levels in
the electrically active nervous system. We combined transgenic expression of an
ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological
recordings of acutely isolated optic nerves. This allowed us to monitor dynamic
changes and activity-dependent axonal ATP homeostasis at the cellular level and
in real time. We find that changes in ATP levels correlate well with compound
action potentials. However, this correlation is disrupted when metabolism of
lactate is inhibited, suggesting that axonal glycolysis products are not
sufficient to maintain mitochondrial energy metabolism of electrically active
axons. The combined monitoring of cellular ATP and electrical activity is a novel
tool to study neuronal and glial energy metabolism in normal physiology and in
models of neurodegenerative disorders.
PMID- 28414270
TI - Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body
adipose hyperplasia, and suppression of leptin expression.
AB - MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane
fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy,
with associated lipodystrophy only occasionally noted, however homozygosity for
the p.Arg707Trp mutation was recently associated with upper body adipose
overgrowth. We describe similar massive adipose overgrowth with suppressed leptin
expression in four further patients with biallelic MFN2 mutations and at least
one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1
negative unilocular adipocytes, with mitochondrial network fragmentation,
disorganised cristae, and increased autophagosomes. There was strong
transcriptional evidence of mitochondrial stress signalling, increased protein
synthesis, and suppression of signatures of cell death in affected tissue,
whereas mitochondrial morphology and gene expression were normal in skin
fibroblasts. These findings suggest that specific MFN2 mutations cause tissue
selective mitochondrial dysfunction with increased adipocyte proliferation and
survival, confirm a novel form of excess adiposity with paradoxical suppression
of leptin expression, and suggest potential targeted therapies.
PMID- 28414272
TI - Regulation of mitochondria-dynactin interaction and mitochondrial retrograde
transport in axons.
AB - Mitochondrial transport in axons is critical for neural circuit health and
function. While several proteins have been found that modulate bidirectional
mitochondrial motility, factors that regulate unidirectional mitochondrial
transport have been harder to identify. In a genetic screen, we found a zebrafish
strain in which mitochondria fail to attach to the dynein retrograde motor. This
strain carries a loss-of-function mutation in actr10, a member of the dynein
associated complex dynactin. The abnormal axon morphology and mitochondrial
retrograde transport defects observed in actr10 mutants are distinct from dynein
and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin
binding domain maintains its ability to bind mitochondria, arguing for a role for
Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies
implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde
transport. Together, this work identifies Actr10 as a factor necessary for
dynactin-mitochondria interaction, enhancing our understanding of how
mitochondria properly localize in axons.
PMID- 28414274
TI - Prepancreatic postduodenal portal vein.
PMID- 28414275
TI - A New Hypothesis on the Frequency Discrimination of the Cochlea.
AB - OBJECTIVE: Medial olivocochlear efferent (MOCE) neurons innervate outer hair
cells (OHCs) of the cochlea, which in turn leads to basilar membrane motion. We
hypothesized that MOCE-induced alterations in basilar membrane motion,
independent of traveling waves, is responsible for the cochlear frequency
discrimination of sound. MATERIALS AND METHODS: Eleven guinea pigs underwent
bilateral otoscopic and audiologic evaluations under general anesthesia. The
study comprised two parts. Part I (n=11) included spontaneous otoacoustic
emission (SOAE) recordings with or without contralateral pure-tone acoustic
stimuli (1 and 8 kHz) at 60 dB sound pressure level (SPL). Part II involved pure
tone (1 or 8 kHz) acoustic trauma in the right ears of two randomly selected
subgroups (G1: 1 kHz; n=4 and G8: 8 kHz; n=4). The remaining three animals served
as controls. After frequency-specific deafness was confirmed by distortion
product otoacoustic emission (DPOAE), SOAEs were recorded in the left ears in the
presence of a contralateral pure-tone (1 and 8 kHz) stimulus of 60 dB SPL.
Furthermore, the surface of the organ of Corti was examined by scanning electron
microscopy (SEM). RESULTS: The contralateral pure tone led to frequency-specific
activation in SOAEs in part I (without trauma) and part II (with trauma)
measurements. SEM showed heterogeneous OHC damage along the cochlea in
traumatized ears with pure tone. CONCLUSION: We suggest that MOCEs convey
acoustic information from traumatized ears to intact ears. Traumatized ears can
show frequency-specific activation in the presence of diffuse damage in OHCs that
excludes the passive transmission of the pressure wave from the perilymph to the
basilar membrane.
PMID- 28414273
TI - Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate
cartilage.
AB - Cartilaginous structures are at the core of embryo growth and shaping before the
bone forms. Here we report a novel principle of vertebrate cartilage growth that
is based on introducing transversally-oriented clones into pre-existing
cartilage. This mechanism of growth uncouples the lateral expansion of curved
cartilaginous sheets from the control of cartilage thickness, a process which
might be the evolutionary mechanism underlying adaptations of facial shape. In
rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing
limbs), the transverse integration of clonal columns determines the well-defined
diameter and resulting rod-like morphology. We were able to alter cartilage shape
by experimentally manipulating clonal geometries. Using in silico modeling, we
discovered that anisotropic proliferation might explain cartilage bending and
groove formation at the macro-scale.
PMID- 28414276
TI - Studying the Association between Sudden Hearing Loss and DNA N-Methyltransferase
1 (DNMT1) Genetic Polymorphism.
AB - OBJECTIVE: The aim of the present study was to investigate whether there was any
relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and
susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL
patients. MATERIAL AND METHODS: We investigated 90 patients diagnosed with ISSHL
and a control group composed of 75 age- and gender-matched healthy individuals.
DNA was extracted from the blood samples by phenol-chloroform method. Polymerase
chain reaction and restriction fragment length polymorphism methods were used for
the genotyping analysis of 4 regions of DNMT1. RESULTS: For rs2228612 single
nucleotide polymorphism (SNP), the frequency of AA, AG, and GG genotypes were
81.4%, 9.3%, and 9.3% in controls and 82.2%, 16.7%, and 1.1% in patients,
respectively. We observed a significant decrease in the frequency of GG genotype
in patients with ISSHL when compared with controls (p=0.027). The frequency of
GG, AG, and AA genotypes for rs2228611 SNP were 20.7%, 49.3%, and 20% in controls
and 20%, 47.8%, and 32.2% in patients, respectively. There was a significantly
increased frequency of the AA genotype of this SNP in the DNMT1 gene, and we
found that individuals with the AA genotype had 2.47 times the risk for ISSHL
development than individuals with the GG genotype (p=0.41). The GAA haplotype may
constitute 2.66 times the risk for ISSHL disease (OR=2.66, 95% confidence
interval: 0.28-25.03). CONCLUSION: This study's results showed that the AA
genotype in rs2228611 polymorphism was a risk factor in ISSHL patients and the GG
genotype could be a protective factor in rs2228612 polymorphism.
PMID- 28414277
TI - Waardenburg Syndrome: An Unusual Indication of Cochlear Implantation Experienced
in 11 Patients.
AB - OBJECTIVE: The aim of this study was to present the surgical findings of children
with Waardenburg syndrome (WS) and investigate speech development after cochlear
implantation in this unique group of patients. MATERIALS AND METHODS: A
retrospective chart review of the patients diagnosed with WS and implanted
between 1998 and 2015 was performed. Categories of auditory performance (CAP)
test were used to assess the auditory skills of these patients. CAP is a
nonlinear hierarchical scale used to rate a child's developing auditory
abilities. Preoperative test results and intraoperative surgical findings of
these patients have been presented. RESULTS: In total, 1835 cases were implanted
a tour institution, and 1210 of these were children. Among these implantees, 11
were diagnosed with WS (0.59% of all implantees). Four of the 11 patients showed
incomplete partition type 2bony labyrinth abnormality (Mondini deformity) and all
patients showed intraoperative gusher during cochleostomy, which was subsided
through routine interventions. No other complications occurred during surgery,
and all patients showed satisfactory CAP results in the late postoperative
period. CONCLUSION: Our experiences with cochlear implantation in patients with
WS showed that the procedure is safe and effective in this group of patients.
Surgeons should be aware of possible labyrinth malformations and intraoperative
problems such as gusher in these patients. In long term, auditory performances
may exhibit satisfactory results with optimal postoperative educational and
supportive measures.
PMID- 28414278
TI - Otoacoustic Emissions in Young Children with Autism.
AB - OBJECTIVE: The aim of this study is to investigate otoacoustic emissions (OAEs)
in young children with autism compared with those in an age-matched control
group. MATERIALS AND METHODS: Thirty-eight children with autism aged 3-6 years
and 27 typically developing (normally developing) control subjects participated
in this study. All the participants had normal hearing and middle-ear function.
Auditory brainstem responses were used to determine the hearing status in the
autism group. Transient-evoked otoacoustic emissions (TEOAEs) and distortion
product otoacoustic emissions (DPOAEs) were measured in the two groups. RESULTS:
The TEOAE response level was higher in the autism group. Analysis of the DPOAE
response showed that the mean emission levels at 1.5, 2 , 3, and 6 kHz and
signal/noise ratios at 2, 4, 6, and 8 kHz were higher in the autism group
(p<0.05). The greatest between-group differences were observed in the DPOAE
signal levels at 2, 3, and 6 kHz (p=0.000). No statistically significant
difference was found between the noise levels in the autism and control groups
(p>0.05). CONCLUSION: The emission responses in the autism group were higher than
those in the control group. The increase in DPOAEs at high frequencies may be
related to the higher outer cell activation in the autism group. Further studies
with larger sample sizes comprising younger children are needed to confirm the
result and investigate the possible association between the increased OAEs and
auditory sensitivity reported in autism.
PMID- 28414279
TI - Short-term Effects of Radioiodine Therapy on Auditory Function.
AB - OBJECTIVE: Radioiodine therapy (RIT) is frequently utilized as an adjunctive
treatment option for differentiated thyroid carcinoma following surgical
intervention. The side effects of RIT are considered to emerge as a result of
radioiodine accumulation in non-thyroidal tissues capable of iodine uptake. We
aimed to evaluate the effects of RIT on auditory function. MATERIALS AND METHODS:
Patients who had undergone total thyroidectomy and diagnosed to have
differentiated thyroid carcinoma were analyzed. Those who were given RIT were
included. Pure-tone audiometry and distortion product otoacoustic emission (DP
OAE) results were recorded along with patient demographics, RIT dose, and thyroid
hormone profiles, both before and 3 months after RIT. RESULTS: Here, 63 patients
were enrolled. Following RIT, audiometric thresholds at 0.25, 0.5, 4, and 8 kHz
in addition to pure-tone average increased significantly; however, the change in
DP-OAE results was not statistically significant at any frequency. The RIT dose
had no effect on auditory function. CONCLUSION: In this study, we found some
deleterious effects of RIT on audiometric thresholds, with no significant effect
on DP-OAE results.
PMID- 28414280
TI - Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Pediatric Patients
with Idiopathic Sudden Hearing Loss.
AB - OBJECTIVE: We investigated the significance of the neutrophil-to-lymphocyte and
platelet-to-lymphocyte ratios, which have recently been used in adults for the
prognosis of idiopathic sudden hearing loss (ISHL), in the prognosis of
idiopathic sudden hearing loss in a pediatric population. MATERIALS AND METHODS:
A total of 13 males and 8 females younger than19 years with idiopathic sudden
hearing loss were retrospectively examined between January 2008 and August
2016.The control group consisted of 12 healthy males and 12 healthy females.
Patients were divided into two groups: those who recovered after treatment and
those who did not. RESULTS: A statistical significance for the neutrophil-to
lymphocyte ratio was detected between the patient group and control group and
between patients who recovered and those who did not (p<0.05). No statistical
significance for the platelet-to-lymphocyte ratio was detected between the
patient group and control group and between patients with recovery and those
without recovery (p>0.05). CONCLUSION: The neutrophil-to-lymphocyte ratio is an
important marker for the prognosis of idiopathic sudden hearing loss in pediatric
patients, similar to its use in adult patients.
PMID- 28414281
TI - [Analysis of contribution of protein phosphorylation in the development of the
diseases].
AB - In recent decades, studies in the molecular origins of socially significant
diseases have made a big step forward with the development and using of high
performance methods in genomics and proteomics. Numerous studies in the framework
of the global program "Human Proteome" were aimed at the identification of all
possible proteins in various cell cultures and tissues, including cancer. One of
the objectives was to identify biomarkers - proteins with high specificity to
certain pathologies. However, in many cases, it is shown that the development of
the disease is not associated with the appearance of new proteins, but depends on
the level of gene expression or forming of proteoforms - splice variants, single
amino acid substitutions (SAP variants), and post-translational modifications
(PTM) of proteins. PTM may play a key role in the development of pathology
because they activate a variety of regulatory or structural proteins in the
majority of cell physiological processes. Phosphorylation is among the most
significant of these protein modifications.This review will describe methods for
analysis of protein phosphorylation used in the studies of such diseases as
cancer and neurodegenerative diseases, as well as examples of cases when the
modified proteins are involved directly to their development, and screening such
significant PTM is used for the diagnosis and choice of treatment.
PMID- 28414282
TI - [Pharmacometabonomics - the novel way to personalized drug therapy].
AB - The review is devoted to pharmacometabonomics - a new branch of science focused
on personalization of drug therapy through the comprehensive analysis of
metabolites of patient's biological fluids. It considers the history of
pharmacometabonomic, positioning to other "-omic" sciences, and system approach,
realized by this science, in determination of individual therapeutic dose of the
drugs and also a technical implementation of pharmacometabonomic based on direct
mass spectrometry of blood plasma metabolites. Special attention is paid to a
comparative analysis of pharmacometabonomics and other main approaches to
personalized therapy in the clinic, such as pharmacogenetics and therapeutic drug
monitoring. Finally, prospects of pharmacometabonomics applications in clinical
practice were also discussed.
PMID- 28414283
TI - [Prediction of protein thermostability from their primary structure: the current
state and development factors].
AB - The construction of proteins and peptides with desired properties, including
resistance to high temperatures, as well as optimization of their amino acid
composition, is an important and complex task, which attracts much attention in
various branches of the basic sciences, and also in biomedicine and
biotechnology. This raises the question: what method is more relevant for the at
the pilot stage of research in order to estimate the influence of the planned
amino acid substitutions on the thermostability of the resultant protein
construct? In this brief review we have classified existing basic practical and
theoretical approaches used in studies and predicting the thermal stability of
native and recombinant polypeptides. Particular attention has been paid to the
predictive potential of statistical methods for studying the thermodynamic
parameters of the primary protein structure and prospects of their use.
PMID- 28414284
TI - [Antineoplastic mechanisms of niclosamide-loaded nanoparticles in human
colorectal cancer cells].
AB - Using poly(lactic-co-glycolic) acid we developed a polymeric form of niclosamide
(PFN) and investigated molecular mechanisms underlying its antitumor activity
against human colorectal cancer cell lines (SW837, Caco-2, COLO 320 HSR). PFN was
shown to be more cytotoxic against cancer cells and less cytotoxic against normal
cells (human embryonic lung fibroblasts) as compared to niclosamide. Both
niclosamide and its polymeric form caused mitochondrial damage (evaluated as a
decrease in rhodamine 123 accumulation) and increased the levels of reactive
oxygen species, particularly mitochondrial superoxide, resulting in the oxidative
damage to biomolecules. Furthermore, niclosamide and PFN induced G0/G1 cell cycle
arrest.
PMID- 28414285
TI - [Analysis of gene expression pattern in peripheral blood leukocytes during
experimental heat wave].
AB - The conditions of Moscow 2010 summer heat wave were simulated in an accommodation
module. Six healthy men aged from 22 to 46 years stayed in the module for 30
days. Measurements of gene expression in peripheral blood leukocytes before,
during and 3 day after simulated heat wave were performed using qRT-PCR. We
observed a shift in the expression level of certain genes after heat exposure for
a long time, and rapid return to the initial level, when volunteers leaved the
accommodation module. Eight genes were chosen to form the "heat expression
signature". EGR2, EGR3 were upregulated in all six volunteers, EGR1, SIRT1,
CYP51A1, MAPK9, BAG5, MNDA were upregulated in 5 volunteers.
PMID- 28414286
TI - [PCR analysis of the absolute number of copies of human chromosome 18 transcripts
in liver and HepG2 cells].
AB - Using reverse transcription in conjunction with the quantitative real-time PCR or
digital droplet PCR, the transcriptome profiling of human chromosome 18 has been
carried out in liver hepatocytes and hepatoblastoma cells (HepG2 cell line) in
terms of the absolute number of each transcript per cell. The transcript
abundance varies within the range of 0.006 to 9635 and 0.011 to 4819 copies per
cell for HepG2 cell line and hepatocytes, respectively. The expression profiles
for genes of chromosome 18 in hepatocytes and HepG2 cells were found to
significantly correlate: the Spearman's correlation coefficient was equal to
0.81. The distribution of frequency of transcripts over their abundance was
bimodal for HepG2 cells and unimodal for liver hepatocytes. Bioinformatic
analysis of the differential gene expression has revealed that genes of
chromosome 18, overexpressed in HepG2 cells compared to hepatocytes, are
associated with cell division and cell adhesion processes. It is assumed that the
enhanced expression of those genes in HepG2 cells is related to the proliferation
activity of cultured cells. The differences in transcriptome profiles have to be
taken into account when modelling liver hepatocytes with cultured HepG2 cells.
PMID- 28414287
TI - [Metabolic effects of combined introduction of adrenalin and blocker of
methanoprolol beta-adrenophyleters].
AB - The effect of combined administration of adrenaline (0.4 mg/kg, i.p.) and b1
blocker metoprolol (25 mg/kg) on the activity of glutathione peroxidase (GPO),
glutathione reductase (GR), catalase, adenosine deaminase (AD), AMP deaminase
(AMPD), 5c-nucleotidase (5cN), on the level ofmalonic dialdehyde (MDA) and
conjugated dienes (CD) was investigated. In blood adrenaline administration to
animals caused an increase in the activity of AMPD, AD, 5cN and GPO, and the
increase the level of CD in the blood increases. Metoprolol caused a more
pronounced increase in the activity of blood AMPD, AD, 5'N and the amount of CD.
In contrast to adrenaline, metoprolol decreased the MDA level of, and decreased
the activity of GPO and catalase. Combined administration of metoprolol and
adrenaline to animals was accompanied by an increase in the activity of AD, AMPD,
5cN, a decrease in the activity of GR, GPO, catalase, and a decrease in MDA in
the blood. In the heart, adrenaline injection was accompanied by an increase in
the MDA level, a decrease in 5cN activity and an increase in the ratio of the
activities of the enzymes AD+AMPD/5cN. Metoprolol injection reduced MDA and CD
levels and the activity of GR and GPO. The combined administration of metoprolol
and adrenaline in the heart was accompanied by activation of AD, AMPD and 5cN,
and a decrease in the amount of MDA and CD, and a decrease in the activity of GR,
GPO, and catalase. In the liver adrenaline caused an increase in MDA and DC
levels, activation of catalase, AD, AMPD, and 5cN. Metoprolol caused a decrease
in MDA and CD levels and activity of catalase and GPO, an increase in the
activity of AD and AMPD in the liver. Combined administration of adrenaline and
metoprolol reduced manifestations of the heart and liver oxidative stress
response as compared with administration of adrenaline alone.
PMID- 28414288
TI - [Redox-dependent mechanisms of regulation of breast epithelial cell
proliferation].
AB - Activation of free radical oxidation in different cell types, including breast
epithelial cells, may result in damage to macromolecules, in particular, proteins
taking part in regulation of cell proliferation and apoptosis. The glutathione,
glutaredoxin and thioredoxin systems play an essential role in maintaining
intracellular redox homeostasis. Due to this fact, modulation of cellular redox
status under the effect of an SH group inhibitor and an SH group protector may be
used as a model for studying the role of redox proteins and glutathione in
regulating cell proliferation in different pathological processes. In this study
we have evaluated the state of the thioredoxin, glutaredoxin and glutathione
systems as well as their role in regulating proliferation of HBL-100 breast
epithelial cells under redox status modulation with N-ethylmaleimide (NEM) and
1,4-dithioerythriol (DTE). Modulating the redox status of breast epithelial cells
under the effect of NEM and DTE influences the functional activity of glutathione
dependent enzymes, glutaredoxin, thioredoxin, and thioredoxin reductase through
changes in the GSH and GSSG concentrations. In HBL-100 cells under redox-status
modulation, we have found an increase in the number of cells in the S-phase of
the cell cycle and a decrease in the number of cells in the G0/G1 and G2/M
phases, as opposed to the values in the intact culture. The proposed model of
proliferative activity of cells under redox status modulation may be used for
development of new therapeutic approaches for treatment of diseases accompanied
by oxidative stress generation.
PMID- 28414289
TI - [Isolation and characterization of exosomes from blood plasma of breast cancer
and colorectal cancer patients].
AB - A simple approach for isolation of exosomes from the blood plasma, which allows
to obtain highly purified preparations of microvesicles no larger than 100 nm has
been proposed. The presence of different subpopulations of exosomes in the blood
plasma of healthy donors and cancer patients has been recognized. We found the
presence of the universal markers CD9, CD24 and CD81 on exosomes isolated from
blood plasma that can be used to their routine typing.
PMID- 28414290
TI - [The effect of isatin on protein-protein interactions between cytochrome b5 and
cytochromes P450].
AB - Cytochromes P450 (CYP) are involved in numerous biochemical processes including
metabolism of xenobiotics, biosynthesis of cholesterol, steroid hormones etc.
Since some CYP catalyze indol oxidation to isatin, we have hypothesized that
isatin can regulate protein-protein interactions (PPI) between components of the
CYP system thus representing a (negative?) feedback mechanism. The aim of this
study was to investigate a possible effect of isatin on interaction of human CYP
with cytochrome b5 (CYB5A). Using the optical biosensor test system employing
surface plasmon resonance (SPR) we have investigated interaction of immobilized
CYB5A with various CYP in the absence and in the presence of isatin. The SPR
based experiments have shown that a high concentration of isatin (270 mM)
increases Kd values for complexes CYB5A/CYP3A5 and CYB5A/CYP3A4 (twofold and
threefold, respectively), but has no influence on complex formation between CYB5A
and other CYP (including indol-metabolizing CYP2C19 and CYP2E1). Isatin injection
to the optical biosensor chip with the preformed molecular complex CYB5A/CYP3A4
caused a 30%-increase in its dissociation rate. Molecular docking manipulations
have shown that isatin can influence interaction of CYP3A5 or CYP3A4 with CYB5A
acting at the contact region of CYB5A/CYP.
PMID- 28414291
TI - Defects in DNA replication hit NK cells and neutrophils.
AB - Patients who present with unique immunological phenotypes provide an opportunity
to better understand defect-driving mutations. In this issue of the JCI,
Cottineau and colleagues characterize 5 individuals who exhibited growth
restriction, facial deformities, and a history of bacterial and viral infection.
Further characterization revealed that these patients were neutropenic and NK
cell deficient. These phenotypes were unexpectedly linked to mutations in the
gene encoding a subunit of the Go-Ichi-Ni-San (GINS) complex, which is essential
for DNA replication prior to cell division. Together, the results of this study
lay the groundwork for future studies to explore the role of DNA replication in
immune cell generation and function.
PMID- 28414292
TI - Dendritic cells expressing immunoreceptor CD300f are critical for controlling
chronic gut inflammation.
AB - Proinflammatory cytokine overproduction and excessive cell death, coupled with
impaired clearance of apoptotic cells, have been implicated as causes of failure
to resolve gut inflammation in inflammatory bowel diseases. Here we have found
that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f
play a crucial role in regulating gut inflammatory responses in a murine model of
colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate
sodium-induced colonic inflammation as a result of defects in dendritic cell
function that were associated with abnormal accumulation of apoptotic cells in
the gut. CD300f-deficient dendritic cells displayed hyperactive phagocytosis of
apoptotic cells, which stimulated excessive TNF-alpha secretion predominantly
from dendritic cells. This, in turn, induced secondary IFN-gamma overproduction
by colonic T cells, leading to prolonged gut inflammation. Our data highlight a
previously unappreciated role for dendritic cells in controlling gut homeostasis
and show that CD300f-dependent regulation of apoptotic cell uptake is essential
for suppressing overactive dendritic cell-mediated inflammatory responses,
thereby controlling the development of chronic gut inflammation.
PMID- 28414293
TI - Inherited GINS1 deficiency underlies growth retardation along with neutropenia
and NK cell deficiency.
AB - Inborn errors of DNA repair or replication underlie a variety of clinical
phenotypes. We studied 5 patients from 4 kindreds, all of whom displayed
intrauterine growth retardation, chronic neutropenia, and NK cell deficiency.
Four of the 5 patients also had postnatal growth retardation. The association of
neutropenia and NK cell deficiency, which is unusual among primary
immunodeficiencies and bone marrow failures, was due to a blockade in the bone
marrow and was mildly symptomatic. We discovered compound heterozygous rare
mutations in Go-Ichi-Ni-San (GINS) complex subunit 1 (GINS1, also known as PSF1)
in the 5 patients. The GINS complex is essential for eukaryotic DNA replication,
and homozygous null mutations of GINS component-encoding genes are embryonic
lethal in mice. The patients' fibroblasts displayed impaired GINS complex
assembly, basal replication stress, impaired checkpoint signaling, defective cell
cycle control, and genomic instability, which was rescued by WT GINS1. The
residual levels of GINS1 activity reached 3% to 16% in patients' cells, depending
on their GINS1 genotype, and correlated with the severity of growth retardation
and the in vitro cellular phenotype. The levels of GINS1 activity did not
influence the immunological phenotype, which was uniform. Autosomal recessive,
partial GINS1 deficiency impairs DNA replication and underlies intra-uterine (and
postnatal) growth retardation, chronic neutropenia, and NK cell deficiency.
PMID- 28414294
TI - Salt and water: not so simple.
AB - It has long been viewed that the maintenance of osmotic balance in response to
high salt intake is a passive process that is mediated largely by increased water
consumption to balance the salt load. Two studies in this issue of the JCI
challenge this notion and demonstrate that osmotic balance in response to high
salt intake involves a complex regulatory process that is influenced by hormone
fluctuation, metabolism, food consumption, water intake, and renal salt and water
excretion. Rakova et al. report the unexpected observation that long-term high
salt intake did not increase water consumption in humans but instead increased
water retention. Moreover, salt and water balance was influenced by
glucocorticoid and mineralocorticoid fluctuations. Kitada et al. extend upon
these findings in mouse models and determined that increased urea and a
corresponding increase in urea transporters in the renal medulla as the result of
increased protein intake promote the water retention that is needed to achieve
osmotic homeostasis. Together, the results of these two studies lay the
groundwork for future studies to determine how, in the face of chronic changes in
salt intake, humans maintain volume and osmotic homeostasis.
PMID- 28414295
TI - High salt intake reprioritizes osmolyte and energy metabolism for body fluid
conservation.
AB - Natriuretic regulation of extracellular fluid volume homeostasis includes
suppression of the renin-angiotensin-aldosterone system, pressure natriuresis,
and reduced renal nerve activity, actions that concomitantly increase urinary Na+
excretion and lead to increased urine volume. The resulting natriuresis-driven
diuretic water loss is assumed to control the extracellular volume. Here, we have
demonstrated that urine concentration, and therefore regulation of water
conservation, is an important control system for urine formation and
extracellular volume homeostasis in mice and humans across various levels of salt
intake. We observed that the renal concentration mechanism couples natriuresis
with correspondent renal water reabsorption, limits natriuretic osmotic diuresis,
and results in concurrent extracellular volume conservation and concentration of
salt excreted into urine. This water-conserving mechanism of dietary salt
excretion relies on urea transporter-driven urea recycling by the kidneys and on
urea production by liver and skeletal muscle. The energy-intense nature of
hepatic and extrahepatic urea osmolyte production for renal water conservation
requires reprioritization of energy and substrate metabolism in liver and
skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven
muscle catabolism, which are prevented by increasing food intake. This
natriuretic-ureotelic, water-conserving principle relies on metabolism-driven
extracellular volume control and is regulated by concerted liver, muscle, and
renal actions.
PMID- 28414296
TI - PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor
CD8+ T cells.
AB - Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and
the immunostimulatory molecule CD80 and functions as a checkpoint to regulate
immune responses. The interaction of PD-L1 with CD80 alone has been shown to
exacerbate the severity of graft-versus-host disease (GVHD), whereas
costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that
temporary depletion of donor CD4+ T cells early after hematopoietic cell
transplantation effectively prevents GVHD while preserving strong graft-versus
leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models. Depletion
of donor CD4+ T cells increased serum IFN-gamma but reduced IL-2 concentrations,
leading to upregulation of PD-L1 expression by recipient tissues and donor CD8+ T
cells. In GVHD target tissues, the interactions of PD-L1 with PD-1 on donor CD8+
T cells cause anergy, exhaustion, and apoptosis, thereby preventing GVHD. In
lymphoid tissues, the interactions of PD-L1 with CD80 augment CD8+ T cell
expansion without increasing anergy, exhaustion, or apoptosis, resulting in
strong GVL effects. These results indicate that the outcome of PD-L1-mediated
signaling in CD8+ T cells depends on the presence or absence of CD4+ T cells, the
nature of the interacting receptor expressed by CD8+ T cells, and the tissue
environment in which the signaling occurs.
PMID- 28414298
TI - Access granted: iRGD helps silicasome-encased drugs breach the tumor barrier.
AB - In this issue of the JCI, Liu et al. use irinotecan-loaded nanoparticles to treat
pancreatic adenocarcinomas in mice. Encapsulating drugs into nanoparticles has
distinct advantages: it can improve the pharmacokinetics of the drug, enhance
efficacy, and reduce unwanted side effects. A drawback is that the large size of
nanoparticles restricts their access to the tumor interior. Liu and colleagues
show that the cyclic tumor-penetrating peptide iRGD, reported to be capable of
enhancing tumor penetration by drugs, can overcome this limitation to a
substantial degree when administered together with the nanoparticles. Pancreatic
adenocarcinoma is a challenging malignancy to treat and in desperate need for
improved treatments; therefore, advances like this are most welcome.
PMID- 28414297
TI - Tumor-penetrating peptide enhances transcytosis of silicasome-based chemotherapy
for pancreatic cancer.
AB - Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some
improvement in overall survival has been achieved with the introduction of
nanocarriers that deliver irinotecan or paclitaxel. Although it is generally
assumed that nanocarriers rely principally on abnormal leaky vasculature for
tumor access, a transcytosis transport pathway that is regulated by neuropilin-1
(NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by
the cyclic tumor-penetrating peptide iRGD. In a KRAS-induced orthotopic PDAC
model, coadministration of iRGD enhanced the uptake of an irinotecan-loaded
silicasome carrier that comprises lipid bilayer-coated mesoporous silica
nanoparticles (MSNPs); this uptake resulted in enhanced survival and markedly
reduced metastasis. Further, ultrastructural imaging of the treated tumors
revealed that iRGD coadministration induced a vesicular transport pathway that
carried Au-labeled silicacomes from the blood vessel lumen to a perinuclear site
within cancer cells. iRGD-mediated enhancement of silicasome uptake was also
observed in patient-derived xenografts, commensurate with the level of NRP-1
expression on tumor blood vessels. These results demonstrate that iRGD enhances
the efficacy of irinotecan-loaded silicasome-based therapy and may be a suitable
adjuvant in nanoparticle-based treatments for PDAC.
PMID- 28414299
TI - An indirect route to repetitive actions.
AB - It is increasingly evident that there is a genetic contribution to autism
spectrum disorders (ASDs) and other neural disorders involving excessive
repetition of action sequences. Among the implicated genes in these disorders are
those encoding postsynaptic scaffolding proteins with roles in synaptic
transmission and plasticity. Several mouse models harboring synonymous mutations
have shown alterations in synaptic transmission within the striatum, which has
key roles in controlling actions and action sequences. In this issue of the JCI,
Wang and coworkers show that glutamatergic synaptic transmission onto striatal
projection neurons is weakened in mutant mice lacking the SH3 and multiple
ankyrin repeat domains 3 (SHANK3B) scaffolding protein, defective expression of
which has been implicated in ASDs. This synaptic alteration gives rise to
stronger activity in the indirect pathway accompanied by decreased dendritic
spines on the indirect pathway medium spiny projection neuron, indicative of
decreased numbers of glutamatergic synapses. Selectively enhancing activity in
this pathway reduced excessive repetitive grooming in the mutant mice. Changes in
glutamatergic input to striatal projection neurons have been observed in several
other murine ASD models and associated disorders. Thus, manipulation of the
function of the striatal indirect pathway may be a useful therapeutic target for
treating disorders characterized by excessive repetitive behaviors.
PMID- 28414300
TI - PD-L1 serves as a double agent in separating GVL from GVHD.
AB - Allogeneic hematopoietic cell transplantation (HCT) represents a potentially
curative treatment for a variety of hematologic malignancies due to the well
recognized graft-versus-leukemia/lymphoma (GVL) effect that is mediated by donor
derived alloreactive T cells. However, graft-versus-host disease (GVHD) is
mediated by the same T cells and remains a significant clinical problem
associated with substantial morbidity and mortality. In this issue of the JCI, Ni
and colleagues used several murine models of GVHD to evaluate the effect of CD4+
T cell depletion on GVL versus GVHD and revealed that depletion of CD4+ T cells
leads to the upregulation of PD-L1 by recipient tissues and donor CD8+ T cells.
Interaction of PD-L1 with PD-1 in GVHD-targeted tissues resulted in CD8+ T cell
exhaustion and apoptosis, thereby preventing GVHD, whereas PD-L1 interactions
with CD80 in lymphoid tissue promoted CD8+ T cell survival and expansion, thereby
enhancing the GVL response. By separating these seemingly similar alloreactive T
cell responses based on the context of interaction, the results of this study may
lay the groundwork for the development of effective clinical strategies to
enhance GVL while minimizing GVHD following allogeneic HCT.
PMID- 28414301
TI - Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient
model of autism.
AB - The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3
(SHANK3) is critical for the development and function of glutamatergic synapses.
Disruption of the SHANK3-encoding gene has been strongly implicated as a
monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and
social interaction deficits. Although basal ganglia dysfunction has been proposed
to underlie repetitive behaviors, few studies have provided direct evidence to
support this notion and the exact cellular mechanisms remain largely unknown.
Here, we utilized the Shank3B mutant mouse model of autism to investigate how
Shank3 mutation may differentially affect striatonigral (direct pathway) and
striatopallidal (indirect pathway) medium spiny neurons (MSNs) and its relevance
to repetitive grooming behavior in Shank3B mutant mice. We found that Shank3
deletion preferentially affects synapses onto striatopallidal MSNs.
Striatopallidal MSNs showed profound defects, including alterations in synaptic
transmission, synaptic plasticity, and spine density. Importantly, the repetitive
grooming behavior was rescued by selectively enhancing the striatopallidal MSN
activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq), a type of
designer receptors exclusively activated by designer drugs (DREADD). Our findings
directly demonstrate the existence of distinct changes between 2 striatal
pathways in a mouse model of autism and indicate that the indirect striatal
pathway disruption might play a causative role in repetitive behavior of Shank3B
mutant mice.
PMID- 28414302
TI - Increased salt consumption induces body water conservation and decreases fluid
intake.
AB - BACKGROUND: The idea that increasing salt intake increases drinking and urine
volume is widely accepted. We tested the hypothesis that an increase in salt
intake of 6 g/d would change fluid balance in men living under ultra-long-term
controlled conditions. METHODS: Over the course of 2 separate space flight
simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3
salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained
constant. We studied the effect of salt-driven changes in mineralocorticoid and
glucocorticoid urinary excretion on day-to-day osmolyte and water balance.
RESULTS: A 6-g/d increase in salt intake increased urine osmolyte excretion, but
reduced free-water clearance, indicating endogenous free water accrual by urine
concentration. The resulting endogenous water surplus reduced fluid intake at the
12-g/d salt intake level. Across all 3 levels of salt intake, half-weekly and
weekly rhythmical mineralocorticoid release promoted free water reabsorption via
the renal concentration mechanism. Mineralocorticoid-coupled increases in free
water reabsorption were counterbalanced by rhythmical glucocorticoid release,
with excretion of endogenous osmolyte and water surplus by relative urine
dilution. A 6-g/d increase in salt intake decreased the level of rhythmical
mineralocorticoid release and elevated rhythmical glucocorticoid release. The
projected effect of salt-driven hormone rhythm modulation corresponded well with
the measured decrease in water intake and an increase in urine volume with
surplus osmolyte excretion. CONCLUSION: Humans regulate osmolyte and water
balance by rhythmical mineralocorticoid and glucocorticoid release, endogenous
accrual of surplus body water, and precise surplus excretion. FUNDING: Federal
Ministry for Economics and Technology/DLR; the Interdisciplinary Centre for
Clinical Research; the NIH; the American Heart Association (AHA); the Renal
Research Institute; and the TOYOBO Biotechnology Foundation. Food products were
donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda,
and Unilever.
PMID- 28414303
TI - Development of potent class II transactivator gene delivery systems capable of
inducing de novo MHC II expression in human cells, in vitro and ex vivo.
AB - Class II transactivator (CIITA) induces transcription of major histocompatibility
complex (MHC) II genes and can potentially be used to improve genetic
immunotherapies by converting non-immune cells into cells capable of presenting
antigens to CD4+ T cells. However, CIITA expression is tightly controlled and it
remains unclear whether distinct non-immune cells differ in this transactivator
regulation. Here we describe the development of gene delivery systems capable of
promoting the efficient CIITA expression in non-immune cell lines and in primary
human cells of an ex vivo skin explant model. Different human cell types
undergoing CIITA overexpression presented high-level de novo expression of MHC
II, validating the delivery systems as suitable tools for the CIITA evaluation as
a molecular adjuvant for gene therapies.
PMID- 28414304
TI - Transforming activity and therapeutic targeting of C-terminal-binding protein 2
in Apc-mutated neoplasia.
AB - Overexpression of the transcriptional coregulators C-terminal binding proteins 1
and 2 (CtBP1 and 2) occurs in many human solid tumors and is associated with poor
prognosis. CtBP modulates oncogenic gene expression programs and is an emerging
drug target, but its oncogenic role is unclear. Consistent with this oncogenic
potential, exogenous CtBP2 transformed primary mouse and human cells to anchorage
independence similarly to mutant H-Ras. To investigate CtBP's contribution to in
vivo tumorigenesis, Apcmin/+ mice, which succumb to massive intestinal polyposis,
were bred to Ctbp2+/- mice. CtBP interacts with adenomatous polyposis coli (APC)
protein, and is stabilized in both APC-mutated human colon cancers and Apcmin/+
intestinal polyps. Ctbp2 heterozygosity increased the median survival of Apcmin/+
mice from 21 to 48 weeks, and reduced polyp formation by 90%, with Ctbp2+/-
polyps exhibiting reduced levels of beta-catenin and its oncogenic
transcriptional target, cyclin D1. CtBP's potential as a therapeutic target was
studied by treating Apcmin/+ mice with the CtBP small-molecule inhibitors 4
methylthio-2-oxobutyric acid and 2-hydroxy-imino phenylpyruvic acid, both of
which reduced polyposis by more than half compared with vehicle treatment.
Phenocopying Ctbp2 deletion, both Ctbp inhibitors caused substantial decreases in
the protein level of Ctbp2, as well its oncogenic partner beta-catenin, and the
effects of the inhibitors on CtBP and beta-catenin levels could be modeled in an
APC-mutated human colon cancer cell line. CtBP2 is thus a druggable transforming
oncoprotein critical for the evolution of neoplasia driven by Apc mutation.
PMID- 28414305
TI - SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination
and turnover of c-MYC oncoprotein.
AB - The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently
dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or
mRNA downregulation, suggesting an important tumour suppressor function. To
examine its physiologic role in the prostate epithelium in vivo, we generated
mice with prostate-specific biallelic ablation of Spop. These mice exhibited
increased prostate mass, prostate epithelial cell proliferation, and expression
of c-MYC protein compared to littermate controls, and eventually developed
prostatic intraepithelial neoplasia (PIN). We found that SPOPWT can physically
interact with c-MYC protein and, upon exogenous expression in vitro, can promote
c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by
introducing PC-associated SPOP mutants or upon knockdown of SPOP via short
hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein
levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in
transcriptomic signatures associated with SPOPMT. Likewise, we observed strong
inverse correlation between c-MYC activity and SPOP mRNA levels in two
independent PC patient cohorts. The core SPOPMT;MYCHigh transcriptomic response,
defined by the overlap between the SPOPMT and c-MYC transcriptomic programmes,
was also associated with inferior clinical outcome in human PCs. Finally, the
organoid-forming capacity of Spop-null murine prostate cells was more sensitive
to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC
upregulation functionally contributes to the proliferative phenotype of Spop
knock-out prostates. Taken together, our data highlight SPOP as an important
regulator of luminal epithelial cell proliferation and c-MYC expression in
prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help
explain the frequent inactivation of SPOP in human PC. We propose SPOPMT-induced
stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC
levels in PC cells, in addition to amplification of c-MYC locus.
PMID- 28414306
TI - Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours.
AB - KRAS is one of the most frequently mutated oncogenes in human non-small cell lung
cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways
including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector
protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular
mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1
(PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF
with PHB1 at the plasma membrane is essential for CRAF activation. Here, we
demonstrate that PHB1 is highly expressed in NSCLC patients and correlates with
poor survival. Targeting of PHB1 with two chemical ligands (rocaglamide and
fluorizoline) inhibits epidermal growth factor (EGF)/RAS-induced CRAF activation.
Consistently, treatment with rocaglamide inhibited proliferation, migration and
anchorage-independent growth of KRAS-mutated lung carcinoma cell lines.
Surprisingly, rocaglamide treatment inhibited Ras-GTP loading in KRAS-mutated
cells as well as in EGF-stimulated cells. Rocaglamide treatment further prevented
the oncogenic growth of KRAS-driven lung cancer allografts and xenografts in
mouse models. Our results suggest rocaglamide as a RAS inhibitor and that
targeting plasma membrane-associated PHB1 with chemical ligands would be a viable
therapeutic strategy to combat KRAS-mediated NSCLCs.
PMID- 28414307
TI - Metabolic inhibitors accentuate the anti-tumoral effect of HDAC5 inhibition.
AB - The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has
firmly laid the cancer community to explore HDAC inhibition as a therapeutic
approach for cancer treatment. Hitting one HDAC member could yield clinical
benefit but this required a complete understanding of the functions of the
different HDAC members. Here we explored the consequences of specific HDAC5
inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron
dependent reactive oxygen species (ROS) production, ultimately leading to
apoptotic cell death as well as mechanisms of mitochondria quality control
(mitophagy and mitobiogenesis). Interestingly, adaptation of HDAC5-depleted cells
to oxidative stress passes through reprogramming of metabolic pathways towards
glucose and glutamine. Therefore, interference with both glucose and glutamine
supply in HDAC5-inhibited cancer cells significantly increases apoptotic cell
death and reduces tumour growth in vivo; providing insight into a valuable
clinical strategy combining the selective inhibition of HDAC5 with various
inhibitors of metabolism as a new therapy to kill cancer cells.
PMID- 28414308
TI - Complex regulation of LCoR signaling in breast cancer cells.
AB - Ligand-dependent corepressor (LCoR) is a transcriptional repressor of ligand
activated estrogen receptors (ERs) and other transcription factors that acts both
by recruiting histone deacetylases and C-terminal binding proteins. Here, we
first studied LCOR gene expression in breast cancer cell lines and tissues. We
detected two mRNAs variants, LCoR and LCoR2 (which encodes a truncated LCoR
protein). Their expression was highly correlated and localized in discrete
nuclear foci. LCoR and LCoR2 strongly repressed transcription, inhibited estrogen
induced target gene expression and decreased breast cancer cell proliferation. By
mutagenesis analysis, we showed that the helix-turn-helix domain of LCoR is
required for these effects. Using in vitro interaction, coimmunoprecipitation,
proximity ligation assay and confocal microscopy experiments, we found that
receptor-interacting protein of 140 kDa (RIP140) is a LCoR and LCoR2 partner and
that this interaction requires the HTH domain of LCoR and RIP140 N- and C
terminal regions. By increasing or silencing LCoR and RIP140 expression in human
breast cancer cells, we then showed that RIP140 is necessary for LCoR inhibition
of gene expression and cell proliferation. Moreover, LCoR and RIP140 mRNA levels
were strongly correlated in breast cancer cell lines and biopsies. In addition,
RIP140 positively regulated LCoR expression in human breast cancer cells and in
transgenic mouse models. Finally, their expression correlated with overall
survival of patients with breast cancer. Taken together, our results provide new
insights into the mechanism of action of LCoR and RIP140 and highlight their
strong interplay for the control of gene expression and cell proliferation in
breast cancer cells.
PMID- 28414309
TI - Tumor-derived fibulin-3 activates pro-invasive NF-kappaB signaling in
glioblastoma cells and their microenvironment.
AB - Molecular profiling of glioblastomas has revealed the presence of key signaling
hubs that contribute to tumor progression and acquisition of resistance. One of
these main signaling mechanisms is the nuclear factor-kappa B (NF-kappaB)
pathway, which integrates multiple extracellular signals into transcriptional
programs for tumor growth, invasion and maintenance of the tumor-initiating
population. We show here that an extracellular protein released by glioblastoma
cells, fibulin-3, drives oncogenic NF-kappaB in the tumor and increases NF-kappaB
activation in peritumoral astrocytes. Fibulin-3 expression correlates with a NF
kappaB-regulated 'invasive signature' linked to poorer survival, being a possible
tissue marker for regions of active tumor progression. Accordingly, fibulin-3
promotes glioblastoma invasion in a manner that requires NF-kappaB activation
both in the tumor cells and their microenvironment. Mechanistically, we found
that fibulin-3 activates the metalloprotease ADAM17 by competing with its
endogenous inhibitor, TIMP3. This results in sustained release of soluble tumor
necrosis factor alpha (TNFalpha) by ADAM17, which in turn activates TNF receptors
and canonical NF-kappaB signaling. Taken together, our results underscore fibulin
3 as a novel extracellular signal with strong activating effect on NF-kappaB in
malignant gliomas. Because fibulin-3 is produced de novo in these tumors and is
absent from the normal brain, we propose that targeting the fibulin-3/NF-kappaB
axis may provide a novel avenue to disrupt oncogenic NF-kappaB signaling in
combination therapies for malignant brain tumors.
PMID- 28414310
TI - Autophagy supports generation of cells with high CD44 expression via modulation
of oxidative stress and Parkin-mediated mitochondrial clearance.
AB - High CD44 expression is associated with enhanced malignant potential in
esophageal squamous cell carcinoma (ESCC), among the deadliest of all human
carcinomas. Although alterations in autophagy and CD44 expression are associated
with poor patient outcomes in various cancer types, the relationship between
autophagy and cells with high CD44 expression remains incompletely understood. In
transformed oesophageal keratinocytes, CD44Low-CD24High (CD44L) cells give rise
to CD44High-CD24-/Low (CD44H) cells via epithelial-mesenchymal transition (EMT)
in response to transforming growth factor (TGF)-beta. We couple patient samples
and xenotransplantation studies with this tractable in vitro system of CD44L to
CD44H cell conversion to investigate the functional role of autophagy in
generation of cells with high CD44 expression. We report that high expression of
the autophagy marker cleaved LC3 expression correlates with poor clinical outcome
in ESCC. In ESCC xenograft tumours, pharmacological autophagy inhibition with
chloroquine derivatives depletes cells with high CD44 expression while promoting
oxidative stress. Autophagic flux impairment during EMT-mediated CD44L to CD44H
cell conversion in vitro induces mitochondrial dysfunction, oxidative stress and
cell death. During CD44H cell generation, transformed keratinocytes display
evidence of mitophagy, including mitochondrial fragmentation, decreased
mitochondrial content and mitochondrial translocation of Parkin, essential in
mitophagy. RNA interference-mediated Parkin depletion attenuates CD44H cell
generation. These data suggest that autophagy facilitates EMT-mediated CD44H
generation via modulation of redox homeostasis and Parkin-dependent mitochondrial
clearance. This is the first report to implicate mitophagy in regulation of
tumour cells with high CD44 expression, representing a potential novel
therapeutic avenue in cancers where EMT and CD44H cells have been implicated,
including ESCC.
PMID- 28414311
TI - A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in
obesity.
AB - In obesity, inflammation of white adipose tissue (AT) is associated with
diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic
and energy-dissipating function mediated by beige adipocytes that express the
uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory
mechanism of beige adipogenesis in obesity that required direct adhesive
interactions between macrophages and adipocytes mediated by the integrin alpha4
and its counter-receptor VCAM-1, respectively; expression of the latter was
upregulated in obesity. This adhesive interaction reciprocally and concomitantly
modulated inflammatory activation of macrophages and downregulation of UCP1
expression dependent on the kinase Erk in adipocytes. Genetic or pharmacological
inactivation of the integrin alpha4 in mice resulted in elevated expression of
UCP1 and beige adipogenesis of subcutaneous AT in obesity. Our findings,
established in both mouse systems and human systems, reveal a self-sustained
cycle of inflammation-driven impairment of beige adipogenesis in obesity.
PMID- 28414313
TI - Alternative direct stem cell derivatives defined by stem cell location and graded
Wnt signalling.
AB - Adult stem cells provide a renewable source of differentiated cells for a wide
variety of tissues and generally give rise to multiple cell types. Basic
principles of stem cell organization and regulation underlying this behaviour are
emerging. Local niche signals maintain stem cells, while different sets of
signals act outside the niche to diversify initially equivalent stem cell
progeny. Here we show that Drosophila ovarian follicle stem cells (FSCs) produced
two distinct cell types directly. This cell fate choice was determined by the
anterior-posterior position of an FSC and by the magnitude of spatially graded
Wnt pathway activity. These findings reveal a paradigm of immediate
diversification of stem cell derivatives according to stem cell position within a
larger population, guided by a graded niche signal. We also found that FSCs
strongly resemble mammalian intestinal stem cells in many aspects of their
organization, including population asymmetry and dynamic heterogeneity.
PMID- 28414312
TI - High-resolution myogenic lineage mapping by single-cell mass cytometry.
AB - Muscle regeneration is a dynamic process during which cell state and identity
change over time. A major roadblock has been a lack of tools to resolve a
myogenic progression in vivo. Here we capitalize on a transformative technology,
single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell
and previously unrecognized progenitor populations that precede differentiation.
We discovered two cell surface markers, CD9 and CD104, whose combined expression
enabled in vivo identification and prospective isolation of stem and progenitor
cells. Data analysis using the X-shift algorithm paired with single-cell force
directed layout visualization defined a molecular signature of the activated stem
cell state (CD44+/CD98+/MyoD+) and delineated a myogenic trajectory during
recovery from acute muscle injury. Our studies uncover the dynamics of skeletal
muscle regeneration in vivo and pave the way for the elucidation of the
regulatory networks that underlie cell-state transitions in muscle diseases and
ageing.
PMID- 28414314
TI - Cell competition with normal epithelial cells promotes apical extrusion of
transformed cells through metabolic changes.
AB - Recent studies have revealed that newly emerging transformed cells are often
apically extruded from epithelial tissues. During this process, normal epithelial
cells can recognize and actively eliminate transformed cells, a process called
epithelial defence against cancer (EDAC). Here, we show that mitochondrial
membrane potential is diminished in RasV12-transformed cells when they are
surrounded by normal cells. In addition, glucose uptake is elevated, leading to
higher lactate production. The mitochondrial dysfunction is driven by
upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively
regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the
surrounding normal cells, involving filamin, drives the Warburg-effect-like
metabolic alteration. Moreover, using a cell-competition mouse model, we
demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12
transformed cells from intestinal epithelia. These data indicate that non-cell
autonomous metabolic modulation is a crucial regulator for cell competition,
shedding light on the unexplored events at the initial stage of carcinogenesis.
PMID- 28414316
TI - Tuning crystallization pathways through sequence engineering of biomimetic
polymers.
AB - Two-step nucleation pathways in which disordered, amorphous, or dense liquid
states precede the appearance of crystalline phases have been reported for a wide
range of materials, but the dynamics of such pathways are poorly understood.
Moreover, whether these pathways are general features of crystallizing systems or
a consequence of system-specific structural details that select for direct versus
two-step processes is unknown. Using atomic force microscopy to directly observe
crystallization of sequence-defined polymers, we show that crystallization
pathways are indeed sequence dependent. When a short hydrophobic region is added
to a sequence that directly forms crystalline particles, crystallization instead
follows a two-step pathway that begins with the creation of disordered clusters
of 10-20 molecules and is characterized by highly non-linear crystallization
kinetics in which clusters transform into ordered structures that then enter the
growth phase. The results shed new light on non-classical crystallization
mechanisms and have implications for the design of self-assembling polymer
systems.
PMID- 28414315
TI - The EMT-activator Zeb1 is a key factor for cell plasticity and promotes
metastasis in pancreatic cancer.
AB - Metastasis is the major cause of cancer-associated death. Partial activation of
the epithelial-to-mesenchymal transition program (partial EMT) was considered a
major driver of tumour progression from initiation to metastasis. However, the
role of EMT in promoting metastasis has recently been challenged, in particular
concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in
pancreatic cancer. In contrast, we show here that in the same pancreatic cancer
model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model),
the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion
and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization
capacity and in particular phenotypic/metabolic plasticity of tumour cells,
probably causing the observed in vivo effects. Accordingly, we conclude that
different EMT-TFs have complementary subfunctions in driving pancreatic tumour
metastasis. Therapeutic strategies should consider these potential specificities
of EMT-TFs to target these factors simultaneously.
PMID- 28414317
TI - p16 controls epithelial cell growth and suppresses carcinogenesis through
mechanisms that do not require RB1 function.
AB - The p16/RB1 tumor suppressor pathway is inactivated in the vast majority, if not
all, human cancers. The current paradigm is that p16 and RB1 function in a linear
pathway to suppress tumorigenesis; however p16 is preferentially lost in human
cancers suggesting that p16 has critical tumor suppressive functions not mediated
through RB1. Carcinomas arise from transformed epithelial cells and account for
80% of adult malignancies highlighting the need to understand p16/RB1 pathway
function in organ epithelia. Lung cancer is the leading cause of cancer deaths
and is associated with p16/RB1 pathway deregulation. We demonstrate that p16 is
upregulated in the lung epithelium after Rb1 ablation in genetically engineered
mouse models. In contrast to fibroblasts, loss of RB1 family proteins, p107 or
p130, did not result in p16 induction, demonstrating that p16 suppression is a
unique RB1 pocket protein function in the lung epithelium in vivo. p16
upregulation did not induce cellular senescence but rather promoted survival of
RB1-deficient lung epithelial progenitor cells. Mechanistic studies show that p16
protects RB1-deficient cells from DNA damage. Consequently, additional loss of
p16 led to genetic instability and increased susceptibility to cellular
immortalization and transformation. Mice with combined RB1/p16-deficient lungs
developed lung tumors including aggressive metastatic lung cancers. These studies
identify p16 loss as a molecular event that causes genetic instability and
directly demonstrate that p16 protects against DNA damage in the absence of RB1
function providing an explanation for why p16 is preferentially targeted in human
cancers.
PMID- 28414319
TI - MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1alpha regulation.
PMID- 28414318
TI - Initial sites of hepadnavirus integration into host genome in human hepatocytes
and in the woodchuck model of hepatitis B-associated hepatocellular carcinoma.
AB - Hepatitis B virus (HBV) and the closely related woodchuck hepatitis virus (WHV)
are potent carcinogens that trigger development of primary hepatocellular
carcinoma (HCC). The initial sites of hepadnavirus-host genome integration, their
diversity and kinetics of formation can be central to virus persistence and the
initiation and progression of HCC. To recognize the nature of the very early
virus-host interactions, we explored de novo infection of human hepatocyte-like
HepaRG cells with authentic HBV and naive woodchucks with WHV. HepaRG were
analyzed from several minutes post exposure to HBV onwards, whereas woodchuck
liver biopsies at 1 or 3 h and 6 weeks post infection with WHV. Inverse PCR and
clonal sequencing of the amplicons were applied to identify virus-host genomic
junctions. HBV and WHV DNA and their replication intermediates became detectable
in one hour after virus exposure. Concomitantly, HBV DNA integration into various
host genes was detected. Notably, junctions of HBV X gene with retrotransposon
sequences, such as LINE1 and LINE2, became prominent shortly after infection. In
woodchucks, insertion of WHV X and preS sequences into host genome was evident at
1 and 3 h post infection (h.p.i.), confirming that hepadnavirus under natural
conditions integrates into hepatocyte DNA soon after invasion. The HBV and WHV X
gene enhancer II/core promotor sequence most often formed initial junctions with
host DNA. Moreover, multiple virus-virus DNA fusions appeared from 1 h.p.i.
onwards in both infected hepatocytes and woodchuck livers. In summary, HBV DNA
integrates almost immediately after infection with a variety of host's sequences,
among which tandemly repeating non-coding DNAs are common. This study revealed
that HBV can engage mobile genetic elements from the beginning of infection to
induce pro-oncogenic perturbations throughout the host genome. Such swift virus
insertion was also evident in natural hepadnaviral infection in woodchucks.
PMID- 28414320
TI - Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication
stress in cancer cells.
AB - Replication stress is a characteristic feature of cancer cells, which is resulted
from sustained proliferative signaling induced by activation of oncogenes or loss
of tumor suppressors. In cancer cells, oncogene-induced replication stress
manifests as replication-associated lesions, predominantly double-strand DNA
breaks (DSBs). An essential mechanism utilized by cells to repair replication
associated DSBs is homologous recombination (HR). In order to overcome
replication stress and survive, cancer cells often require enhanced HR repair
capacity. Therefore, the key link between HR repair and cellular tolerance to
replication-associated DSBs provides us with a mechanistic rationale for
exploiting synthetic lethality between HR repair inhibition and replication
stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in
replication and HR repair. Here we demonstrate that DNA2 is overexpressed in
pancreatic cancers, one of the deadliest and more aggressive forms of human
cancers, where mutations in the KRAS are present in 90-95% of cases. In addition,
depletion of DNA2 significantly reduces pancreatic cancer cell survival and
xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition.
Finally, we develop a robust high-throughput biochemistry assay to screen for
inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be
efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells
with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion,
including decreased DNA double strand break end resection and attenuation of HR
repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2
selectively attenuates the growth of various cancer cells with oncogene-induced
replication stress. Taken together, our findings open a new avenue to develop a
new class of anticancer drugs by targeting druggable nuclease DNA2. We propose
DNA2 inhibition as new strategy in cancer therapy by targeting replication
stress, a molecular property of cancer cells that is acquired as a result of
oncogene activation instead of targeting currently undruggable oncoprotein itself
such as KRAS.
PMID- 28414321
TI - An orthogonal single-molecule experiment reveals multiple-attempt dynamics of
type IA topoisomerases.
AB - Topoisomerases are enzymes that are involved in maintaining the topological state
of cellular DNA. Their dynamic characteristics remain poorly understood despite
numerous structural, biophysical and biochemical studies. Recent single-molecule
experiments revealed that an important feature of the type IA topoisomerase
mechanism is the presence of pauses between relaxation events. However, these
experiments could not determine whether the protein remains DNA bound during the
pauses or what relationship may exist between protein domain movements and
topological changes in the DNA. By combining two orthogonal single-molecule
techniques, we found that E. coli topoisomerase I constantly changes conformation
when attempting to modify the topology of DNA, but succeeds in only a fraction of
the attempts. Thus, its mechanism can be described as a series of DNA strand
passage attempts that culminate in a successful relaxation event.
PMID- 28414322
TI - Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required
for RBR ligase activity.
AB - RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from
RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which
lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a
catalytic RBR module but are usually autoinhibited and activated via distinct
mechanisms. Recent insights into Parkin regulation predict large, unknown
conformational changes during Parkin activation. However, current data on active
RBR ligases reflect the absence of regulatory domains. Therefore, it remains
unclear how individual RBR ligases are activated, and whether they share a common
mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin
complex, which shows that phosphoubiquitin binding induces movement in the 'in
between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation
of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding
promotes cooperation between Parkin molecules, which suggests a role for
interdomain association in the RBR ligase mechanism.
PMID- 28414323
TI - Pyrimidine tract-binding protein 1 mediates pyruvate kinase M2-dependent
phosphorylation of signal transducer and activator of transcription 3 and
oncogenesis in anaplastic large cell lymphoma.
AB - PKM2 (pyruvate kinase M2), a critical regulator of glycolysis, is phosphorylated
by numerous growth factor receptors and oncogenic tyrosine kinases including NPM
ALK which is expressed in a subset of aggressive T-cell non-Hodgkin lymphomas
known as anaplastic large cell lymphoma, ALK-positive. Our previous work
demonstrated that phosphorylation of Y105-PKM2 by NPM-ALK regulates a major
metabolic shift to promote lymphomagenesis. In addition to its role in
metabolism, recent studies have shown that PKM2 promotes oncogenesis by
phosphorylating nuclear STAT3 (signal transducer and activator of transcription
3) and regulating transcription of genes involved in cell survival and
proliferation. We hypothesized that identification of novel PKM2 interactors
could provide additional insights into its expanding functional role in cancer.
To this end, immunocomplexes of FLAG-tagged PKM2 were isolated from NPM-ALK
positive ALCL (anaplastic large cell lymphoma) cells and subjected to liquid
chromatography tandem mass spectrometry (LC-MS/MS) which led to the
identification of polypyrimidine tract-binding protein (PTBP1) as a novel
interactor of PKM2. The interaction between PTBP1 and PKM2 was restricted to the
nucleus and was dependent on NPM-ALK mediated Y105 phosphorylation of PKM2.
Stable shRNA-mediated silencing of PTBP1 resulted in a marked decrease in pY105
PKM2 and pY705-STAT3 which led to decreased ALCL cell proliferation and colony
formation. Overall, our data demonstrate that PTBP1 interacts with PKM2 and
promotes ALCL oncogenesis by facilitating PKM2-dependent activation of STAT3
within the nucleus.
PMID- 28414324
TI - Correlation between histone acetylation and expression of Notch1 in human lung
carcinoma and its possible role in combined small-cell lung carcinoma.
AB - Combined small-cell lung carcinoma (cSCLC) is composed of small-cell lung
carcinoma (SCLC) admixed with non-small-cell lung carcinoma (NSCLC). Evaluating
the molecular differences between SCLC and NSCLC could lead to a better
understanding of the pathogenesis of such neoplasms. Therefore, in this study, we
investigated the correlation between histone acetylation and Notch1 expression in
lung carcinoma. Using chromatin immunoprecipitation (ChIP) assay, we measured the
level of acetylated histone H3 around the promoter region of Notch1 in SCLC and
NSCLC cells. We then treated SCLC cells with trichostatin A (TSA) and
characterized the level of histone H3 acetylation at Notch1. In addition, TSA
treated cells were injected into immune-compromised mice, for analysis of the ex
vivo tumor xenograft phenotype. The level of acetylated histone H3 surrounding
the Notch1 promoter was lower in lung cancer cells not expressing Notch1. Tumors
originated from TSA-treated SCLC cells occasionally formed an epithelial-like
glandular arrangement of cells; with Notch1 expression and decreased expression
of neuroendocrine (NE) markers. Histone deacetylation around the promoter region
of Notch1 inhibits Notch1 protein expression in SCLC and the restoration of
Notch1 expression in SCLC leads to the concurrent appearance of epithelial-like
areas within the SCLC, which could provide a possible mechanism for histogenesis
of cSCLC.
PMID- 28414325
TI - Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug
therapy through the ABCC1 transporter.
AB - The poor response to drug therapy often seen in hepatocellular carcinoma requires
insight into the molecular interplay responsible for intrinsic or acquired drug
resistance. We previously demonstrated that the CD133-/EpCAM- subpopulation of
the Huh-7 hepatoma cell line features aberrant activation of the hedgehog
signaling (Hh) pathway and chemoresistance. The prevailing hypothesis of the
present study is that hedgehog signaling may govern expression of ATP-binding
cassette (ABC) transporters, which are responsible for drug resistance in the
CD133-/EpCAM- subpopulation. Our aim is to reveal the molecular interplay in the
mediation of drug resistance with a newly established Huh-7 subpopulation
featuring high Hh signaling activity and drug resistance. In this study,
chemoresistance was determined in a newly established Huh-7-DN subpopulation
featuring the CD133-/EpCAM- surface marker profile, aberrant expression of Hh
pathway, and epithelial-mesenchymal transition (EMT). Expression of ABC
transporter proteins (ABCB1, ABCC1, and ABCG2) and Hh transcription factor Gli
1/2 was evaluated with and without Hh signaling antagonists LDE225 or
itraconazole. We found that hedgehog signaling activity as determined by
transfection with a Gli-Lux reporter cassette and gene expression levels tended
to increase from Huh-7 CD133+/EpCAM+ to CD133-/EpCAM-, and the highest levels
were found in Huh-7-DN cells. The Huh-7-DN subpopulation exhibited
characteristics of EMT as evidenced by increased expression of vimentin and loss
of E-cadherin. Sorafenib significantly inhibited the viability of all
subpopulations except the Huh-7-DN subpopulation. Compared with other sorafenib
sensitive subpopulations, the Huh-7-DN subpopulation showed enhanced expression
of Hh transcription factor Gli-2 and ABCC1 transporter protein. Silencing Gli-2
by lentivirus harboring shRNA against Gli-2 or LDE225 significantly suppressed
expression of Gli-2 and ABCC1 genes in Huh-7-DN subpopulation. In conclusion,
aberrant hedgehog signaling activation is linked to poor differentiation,
epithelial-mesenchymal transition, and chemoresistance in the Huh-7-DN
subpopulation. Hedgehog signaling transcription factor Gli-2 appears to be the
primary regulator for drug sensitivity of hepatoma through the ABCC1 transporter.
PMID- 28414326
TI - Mesenchymal stem cells in obesity: insights for translational applications.
AB - Obesity is now a major public health problem worldwide. Lifestyle modification to
reduce the characteristic excess body adiposity is important in the treatment of
obesity, but effective therapeutic intervention is still needed to control what
has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been
withdrawn from market due to adverse side effects. Bariatric surgery therefore
remains the most effective therapy for severe cases, although such surgery is
invasive and researchers continue to seek new control strategies for obesity.
Mesenchymal stem cells (MSCs) are a major source of adipocyte generation, and
studies have been conducted into the potential roles of MSCs in treating obesity.
However, despite significant progress in stem cell research and its potential
applications for obesity, adipogenesis is a highly complex process and the
molecular mechanisms governing MSC adipogenesis remain ill defined. In
particular, successful clinical application of MSCs will require extensive
identification and characterization of the transcriptional regulators controlling
MSC adipogenesis. Since obesity is associated with the incidence of multiple
important comorbidities, an in-depth understanding of the relationship between
MSC adipogenesis and the comorbidities of obesity is also necessary to evaluate
the potential of effective and safe MSC-based therapies for obesity. In addition,
brown adipogenesis is an attractive topic from the viewpoint of therapeutic
innovation and future research into MSC-based brown adipogenesis could lead to a
novel breakthrough. Ongoing stem cell studies and emerging research fields such
as epigenetics are expected to elucidate the complicated mechanisms at play in
MSC adipogenesis and develop novel MSC-based therapeutic options for obesity.
This review discusses the current understanding of MSCs in adipogenesis and their
potential clinical applications for obesity.
PMID- 28414327
TI - A novel antibody against cancer stem cell biomarker, DCLK1-S, is potentially
useful for assessing colon cancer risk after screening colonoscopy.
AB - DCLK1 expression is critically required for maintaining growth of human colon
cancer cells (hCCCs). Human colorectal tumors (CRCs) and hCCCs express a novel
short isoform of DCLK1 (DCLK1-S; isoform 2) from beta-promoter of hDCLK1 gene,
while normal colons express long isoform (DCLK1-L; isoform 1) from 5'(alpha)
promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells
(CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino acids, we
succeeded in generating a monospecific DCLK1-S-Antibody (PS41014), which does not
cross-react with DCLK1-L, and specifically detects CSCs. Subcellular localization
of S/L-isoforms was examined by immune-electron-microscopy (IEM). Surprisingly,
besides plasma membrane and cytosolic fractions, S/L also localized to
nuclear/mitochondrial fractions, with pronounced localization of S-isoform in the
nuclei and mitochondria. Sporadic CRCs develop from adenomas. Screening
colonoscopy is used for detection/resection of growths, and
morphological/pathological criteria are used for risk assessment and
recommendations for follow-up colonoscopy. But, these features are not precise
and majority of the patients will never develop cancer. We hypothesized that
antibody-based assay(s), which identify CSCs, will significantly improve
prognostic value of morphological/pathological criteria. We conducted a pilot
retrospective study with PS41014-Ab, by staining archived adenoma specimens from
patients who developed (high-risk), or did not develop (low-risk) adenocarcinomas
within 10-15 years. PS41014-Ab stained adenomas from initial and follow-up
colonoscopies of high-risk patients, at significantly higher levels (three to
fivefold) than adenomas from low-risk patients, suggesting that PS41014-Ab could
be used as an additional tool for assessing CRC risk. CRC patients, with high
DCLK1-S-expressing tumors (by qRT-PCR), were reported to have worse overall
survival than low expressers. We now report that DCLK1-S-specific Ab may help to
identify high-risk patients at the time of index/screening colonoscopy.
PMID- 28414328
TI - Marginal zone B cells control the response of follicular helper T cells to a high
cholesterol diet.
AB - Splenic marginal zone B (MZB) cells, positioned at the interface between
circulating blood and lymphoid tissue, detect and respond to blood-borne
antigens. Here we show that MZB cells in mice activate a homeostatic program in
response to a high-cholesterol diet (HCD) and regulate both the differentiation
and accumulation of T follicular helper (TFH) cells. Feeding mice an HCD resulted
in upregulated MZB cell surface expression of the immunoregulatory ligand PDL1 in
an ATF3-dependent manner and increased the interaction between MZB cells and pre
TFH cells, leading to PDL1-mediated suppression of TFH cell motility, alteration
of TFH cell differentiation, reduced TFH abundance and suppression of the
proatherogenic TFH response. Our findings reveal a previously unsuspected role
for MZB cells in controlling the TFH-germinal center response to a cholesterol
rich diet and uncover a PDL1-dependent mechanism through which MZB cells use
their innate immune properties to limit an exaggerated adaptive immune response.
PMID- 28414329
TI - Alternatively activated macrophages do not synthesize catecholamines or
contribute to adipose tissue adaptive thermogenesis.
AB - Adaptive thermogenesis is the process of heat generation in response to cold
stimulation. It is under the control of the sympathetic nervous system, whose
chief effector is the catecholamine norepinephrine (NE). NE enhances
thermogenesis through beta3-adrenergic receptors to activate brown adipose tissue
and by 'browning' white adipose tissue. Recent studies have reported that
alternative activation of macrophages in response to interleukin (IL)-4
stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in
the catecholamine synthesis pathway, and that this activation provides an
alternative source of locally produced catecholamines during the thermogenic
process. Here we report that the deletion of Th in hematopoietic cells of adult
mice neither alters energy expenditure upon cold exposure nor reduces browning in
inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in
response to stimulation with IL-4, and conditioned media from IL-4-stimulated
macrophages failed to induce expression of thermogenic genes, such as uncoupling
protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore,
chronic treatment with IL-4 failed to increase energy expenditure in wild-type,
Ucp1-/- and interleukin-4 receptor-alpha double-negative (Il4ra-/-) mice. In
agreement with these findings, adipose-tissue-resident macrophages did not
express TH. Thus, we conclude that alternatively activated macrophages do not
synthesize relevant amounts of catecholamines, and hence, are not likely to have
a direct role in adipocyte metabolism or adaptive thermogenesis.
PMID- 28414330
TI - HIV persistence in tissue macrophages of humanized myeloid-only mice during
antiretroviral therapy.
AB - Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in
its hosts and is never eradicated. One major barrier to eradication is that the
virus infects multiple cell types that may individually contribute to HIV
persistence. Tissue macrophages are critical contributors to HIV pathogenesis;
however, their specific role in HIV persistence during long-term suppressive ART
has not been established. Using humanized myeloid-only mice (MoM), we demonstrate
that HIV infection of tissue macrophages is rapidly suppressed by ART, as
reflected by a rapid drop in plasma viral load and a dramatic decrease in the
levels of cell-associated viral RNA and DNA. No viral rebound was observed in the
plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and
no replication-competent virus was rescued from the tissue macrophages obtained
from these animals. In contrast, in a subset of animals (~33%), a delayed viral
rebound was observed that is consistent with the establishment of persistent
infection in tissue macrophages. These observations represent the first direct
evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.
PMID- 28414331
TI - A new fate mapping system reveals context-dependent random or clonal expansion of
microglia.
AB - Microglia constitute a highly specialized network of tissue-resident immune cells
that is important for the control of tissue homeostasis and the resolution of
diseases of the CNS. Little is known about how their spatial distribution is
established and maintained in vivo. Here we establish a new multicolor
fluorescence fate mapping system to monitor microglial dynamics during steady
state and disease. Our findings suggest that microglia establish a dense network
with regional differences, and the high regional turnover rates found challenge
the universal concept of microglial longevity. Microglial self-renewal under
steady state conditions constitutes a stochastic process. During pathology this
randomness shifts to selected clonal microglial expansion. In the resolution
phase, excess disease-associated microglia are removed by a dual mechanism of
cell egress and apoptosis to re-establish the stable microglial network. This
study unravels the dynamic yet discrete self-organization of mature microglia in
the healthy and diseased CNS.
PMID- 28414332
TI - Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees
and macaques.
AB - While human cognitive abilities are clearly unique, underlying changes in brain
organization and function remain unresolved. Here we characterized the
transcriptome of the cortical layers and adjacent white matter in the prefrontal
cortexes of humans, chimpanzees and rhesus macaques using unsupervised sectioning
followed by RNA sequencing. More than 20% of detected genes were expressed
predominantly in one layer, yielding 2,320 human layer markers. While the bulk of
the layer markers were conserved among species, 376 switched their expression to
another layer in humans. By contrast, only 133 of such changes were detected in
the chimpanzee brain, suggesting acceleration of cortical reorganization on the
human evolutionary lineage. Immunohistochemistry experiments further showed that
human-specific expression changes were not limited to neurons but affected a
broad spectrum of cortical cell types. Thus, despite apparent histological
conservation, human neocortical organization has undergone substantial changes
affecting more than 5% of its transcriptome.
PMID- 28414334
TI - Interband cascade laser-based optical transfer standard for atmospheric carbon
monoxide measurements.
AB - We report on an interband cascade laser (ICL)-absorption spectrometer for
absolute, calibration-free, atmospheric CO amount fraction measurements,
addressing direct traceability of the results. The system combines first
principles direct tunable diode laser absorption spectroscopy (dTDLAS) with a
metrological validation. Using a multipath cell with 76 m path length, our
detection limit is 0.5 nmol/mol at Deltat=14 s. The system is highly linear
(slope: 0.999+/-0.008) in the amount fraction range of 0.1-1000 MUmol/mol and
thus is interesting for industrial as well as environmental applications. The
sensor repeatability at 300 nmol/mol is 0.06 nmol/mol (with Deltat=10 min). The
sensor's absolute response is in excellent agreement with the gravimetric values
of a set of primary gas standards used to test the sensor accuracy. The relative
expanded uncertainty (k=2) of the measured CO amount fraction is 2.8%. Due to
this performance and the calibration-free approach, the spectrometer may be used
as an optical transfer standard (OTS) if gas standards are for whatever reason
not available or applicable, e.g., for airborne instruments. Our dTDLAS approach
has shown excellent stability and accuracy in H2O detection [Appl.
Phys. B116, 883 (2014)APPCDL0721-726910.1007/s00340-014-5775-4] even when
compared to primary standards. We therefore deduce that the ICL spectrometer
(after its adaptation to field conditions, similar to our H2O
spectrometers) has good potential to meet the 2 nmol/mol compatibility goal
stated by the World Meteorological Organization for atmospheric CO measurements,
and serve as an OTS which does not need frequent calibrations using reference
gases.
PMID- 28414333
TI - Dynamic hidden states underlying working-memory-guided behavior.
AB - Recent theoretical models propose that working memory is mediated by rapid
transitions in 'activity-silent' neural states (for example, short-term synaptic
plasticity). According to the dynamic coding framework, such hidden state
transitions flexibly configure memory networks for memory-guided behavior and
dissolve them equally fast to allow forgetting. We developed a perturbation
approach to measure mnemonic hidden states in an electroencephalogram. By
'pinging' the brain during maintenance, we show that memory-item-specific
information is decodable from the impulse response, even in the absence of
attention and lingering delay activity. Moreover, hidden memories are remarkably
flexible: an instruction cue that directs people to forget one item is sufficient
to wipe the corresponding trace from the hidden state. In contrast, temporarily
unattended items remain robustly coded in the hidden state, decoupling
attentional focus from cue-directed forgetting. Finally, the strength of hidden
state coding predicts the accuracy of working-memory-guided behavior, including
memory precision.
PMID- 28414335
TI - Uncertainty quantification and design-of-experiment in absorption-based aqueous
film parameter measurements using Bayesian inference.
AB - Diode laser-based multi-wavelength near-infrared (NIR) absorption in aqueous
films is a promising diagnostic for making temporally resolved, simultaneous
measurements of film thickness, temperature, and concentration of a solute. Our
previous work in aqueous urea solutions aimed at determining simultaneously two
of these system parameters, while the third one must be fixed or specified by
additional measurements. The current work presents a simultaneous NIR absorption
based multi-parameter measurement of thickness, temperature, and solute
concentration coupled with the Bayesian methodology that is used to infer
probability densities for the obtained data. The Bayesian analysis is based on a
temperature- and concentration-dependent spectral database generated with a
Fourier transform infrared spectrometer in the range 5500-8000 cm-1
for water with variable temperature and urea concentration. The concept was first
validated with measurements using a calibration cell. Probability densities in
the measured parameters were quantified using a Markov chain Monte Carlo
algorithm, which were used to derive credibility intervals. As a practical
demonstration, the temporal variation of film thickness, urea concentration, and
liquid temperature were recorded during evaporation of a liquid film deposited on
a transparent heated quartz plate.
PMID- 28414336
TI - Study of propagation of vortex beams in aerosol optical medium.
AB - A theoretical and experimental study of the propagation of vortex laser beams in
a random aerosol medium is presented. The theoretical study is based on the
extended Huygens-Fresnel principle with the generation of a random field, using
the fast Fourier transform. The simulation shows that the stability of vortex
beams to fluctuations of an optical medium falls with rising order of optical
vortices. Moreover, a coherence length (radius) of the random medium is of great
importance. The coherence radius extension affects adversely the conservation of
a beam structure in the random medium. During further free-space propagation,
increasing coherence enables reduction of the negative effects of fluctuations
for beams with high-value topological charges. Experimental studies in the random
aerosol medium have shown that at small distances vortex beams mostly demonstrate
lower stability than a Gaussian beam. However, at considerable distances, vortex
beams start to demonstrate greater stability that may be explained by their
capacity to be regenerated after they passed obstacles.
PMID- 28414337
TI - Development of an incoherent broad-band cavity-enhanced aerosol extinction
spectrometer and its application to measurement of aerosol optical
hygroscopicity.
AB - We report on the development of a blue light-emitting-diode-based incoherent
broad-band cavity-enhanced absorption spectroscopy (IBBCEAS) instrument for the
measurement of the aerosol extinction coefficient at lambda=461 nm. With an
effective absorption path length of 2.8 km, an optimum detection limit of 0.05
Mm-1 (5*10-10 cm-1) was achieved with an
averaging time of 84 s. The baseline drift of the developed spectrometer was
about +/-0.3 Mm-1 over 2.5 h (1sigma standard deviation). The
performance of the system was evaluated with laboratory-generated monodispersed
polystyrene latex (PSL) spheres. The retrieved complex refractive index of PSL
agreed well with previously reported values. The relative humidity (RH)
dependence of the aerosol extinction coefficient was measured using IBBCEAS. The
measured extinction enhancement factor values for 200 nm dry ammonium sulphate
particles at different RH were in good agreement with the modeled values. Field
performance of the aerosol extinction spectrometer was demonstrated at the Hefei
Radiation Observatory site.
PMID- 28414338
TI - Open-path spectroscopic methane detection using a broadband monolithic
distributed feedback-quantum cascade laser array.
AB - Methane is a powerful greenhouse gas that has both natural and anthropogenic
sources. The ability to measure methane using an integrated path length approach
such as an open/long-path length sensor would be beneficial in several
environments for examining anthropogenic and natural sources, including tundra
landscapes, rivers, lakes, landfills, estuaries, fracking sites, pipelines, and
agricultural sites. Here a broadband monolithic distributed feedback-quantum
cascade laser array was utilized as the source for an open-path methane sensor.
Two telescopes were utilized for the launch (laser source) and receiver
(detector) in a bistatic configuration for methane sensing across a 50 m path
length. Direct-absorption spectroscopy was utilized with intrapulse tuning.
Ambient methane levels were detectable, and an instrument precision of 70 ppb
with 100 s averaging and 90 ppb with 10 s averaging was achieved. The sensor
system was designed to work "off the grid" and utilizes batteries that are
rechargeable with solar panels and wind turbines.
PMID- 28414339
TI - Coherent anti-Stokes Raman spectroscopy measurement of ethylene in combustion.
AB - Width-increased dual-pump enhanced coherent anti-Stokes Raman spectroscopy
(WIDECARS) has been developed for spatially and temporally resolved simultaneous
measurement of temperature and mole fraction of most major species in ethylene
air flames. This paper describes a method to infer coherent anti-Stokes Raman
spectroscopy complex susceptibility distributions of the nu3 band of
ethylene from WIDECARS spectra measured in heated mixtures of ethylene and air,
and to use such distributions to fit experimental WIDECARS spectra in an ethylene
air flame. The method is used to measure mole fraction ethylene in a dual-mode
supersonic combustor burning premixed ethylene and air with single-laser-shot
precision (one standard deviation) of +/-0.0025 (absolute).
PMID- 28414340
TI - Comparison of chirped-probe-pulse and hybrid femtosecond/picosecond coherent anti
Stokes Raman scattering for combustion thermometry.
AB - A comparison is made between two ultrashort-pulse coherent anti-Stokes Raman
scattering (CARS) thermometry techniques-hybrid femtosecond/picosecond (fs/ps)
CARS and chirped-probe-pulse (CPP) fs-CARS-that have become standards for high
repetition-rate thermometry in the combustion diagnostics community. These two
variants of fs-CARS differ only in the characteristics of the ps-duration probe
pulse; in hybrid fs/ps CARS a spectrally narrow, time-asymmetric probe pulse is
used, whereas a highly chirped, spectrally broad probe pulse is used in CPP fs
CARS. Temperature measurements were performed using both techniques in near
adiabatic flames in the temperature range 1600-2400 K and for probe time delays
of 0-30 ps. Under these conditions, both techniques are shown to exhibit similar
temperature measurement accuracies and precisions to previously reported values
and to each other. However, it is observed that initial calibration fits to the
spectrally broad CPP results require more fitting parameters and a more robust
optimization algorithm and therefore significantly increased computational cost
and complexity compared to the fitting of hybrid fs/ps CARS data. The optimized
model parameters varied more for the CPP measurements than for the hybrid fs/ps
measurements for different experimental conditions.
PMID- 28414341
TI - Laser-induced atomic emission of silicon nanoparticles during laser-induced
heating.
AB - The temporal luminescence behavior of silicon atoms during and after laser
heating of gas-borne silicon nanoparticles was investigated. Silicon
nanoparticles were formed in the exhaust stream of a microwave plasma reactor at
100 mbar. The observed prompt atomic line intensities correspond with thermal
excitation of the evaporated species. A prompt signal at 251.61 and 288.15 nm
originating from the 3s23p2->3s23p4s transitions
showed a lifetime of 16 ns that matches the documented excited-state lifetime for
the respective transitions. A secondary delayed signal contribution with similar
peak intensities was observed commencing approximately 100-300 ns after the laser
pulse and persisting for hundreds of nanoseconds. This signal contribution is
attributed to electron impact excitation or recombination after electron impact
ionization of the silicon evaporated as a consequence of the laser heating of the
plasma leading to non-thermal population of electronically excited silicon. The
observations support a nanoparticle evaporation model that can be used to recover
nanoparticle sizes from time-resolved LII data.
PMID- 28414342
TI - Laser induced thermal lens microscopy for highly sensitive determination of
captopril.
AB - In this work, a combined flow injection-photo thermal lens microscopy (FI-PTLM)
system was used for highly sensitive determination of captopril as an angiotensin
converting enzyme inhibitor. Captopril has no absorption in the visible range,
but due to its thiol group could interact with gold nanoparticles (GNPs). GNPs,
because of their surface plasmon resonance (SPR), have absorption in the visible
range, but their interaction with a low concentration of captopril shows no
effective change in UV-Vis spectrophotometry because their aggregation is slight.
On the contrary, at the same condition, the PTLM with a visible light source
enables sensitive measurement of this compound. The thiol group of captopril
binds to the surface of GNPs and decreases the SPR. At the optimum condition in
the focal volume of 2.68 fL (f=10-15), the obtained range of linearity
was 50-800 nM. The developed method was successfully applied for the
determination of captopril in human serum and pharmaceutical samples.
PMID- 28414343
TI - Effect of hydrocarbon molecular decomposition on palladium-assisted laser-induced
plasma ablation.
AB - The Q-switched Nd:YAG laser is focused on a palladium target in the control
chamber filled with various hydrocarbon atmospheres (C1-C4) to investigate their
effect on the palladium ablated mass, gas reaction products, and corresponding
plasma parameters (such as electron density Ne and plasma temperature
Te) during molecular decomposition. The plasma parameters arise mainly
from the Pd nanocatalytic activity during the laser-induced plasma process. We
compare synthetic air atmosphere to hydrocarbon media to understand how the
latter generates excess heat via oxygen-free exothermic (recombination)
reactions. Subsequently, this gives rise to more energetic plasma and higher
temperature, regarding the large amount of nanoparticles released into the
plasma. The dynamics of the decomposition/recombination events accompany the
nanocatalyst activity, leading to soot deposition all over the chamber.
PMID- 28414344
TI - Measurement of thickness of highly inhomogeneous crude oil slicks.
AB - As part of the Deepwater Horizon toxicity testing program, a number of
laboratories generated oil slicks in the laboratory to study potential toxic
effects of these oil slicks on aquatic organisms. Understanding the details of
how these slicks affect aquatic organisms requires careful correlation between
slick thickness and the observed detrimental effects. Estimating oil film
thickness on water can be challenging since the traditional color-based technique
used in the field is very imprecise. Also, as we demonstrate here, the films
formed on the water surface are highly nonuniform on a microscale level, and thus
uniform thin film thickness measurement techniques based on optical interference
do not work. In this paper, we present a method that estimates the local
thickness of weathered oil slicks formed on artificial seawater using light
transmission and Beer-Lambert's law. Here, we demonstrate results of careful
calibration together with the actual thickness estimation. Due to the
heterogeneity of the slicks formed, we present slick thickness as a range of
thicknesses collected from multiple points within the oil slick. In all the
experiments we used oil samples provided by the Natural Resource Damage
Assessment toxicity testing program for the Deepwater Horizon oil spill.
Therefore, this study has an important practical value and successfully addresses
unique challenges related to measurements involving complex, viscous, paste-like
heterogeneous substances such as weathered crude oil.
PMID- 28414345
TI - Three-color vibrational CARS thermometry of fuel-rich ethylene/air flames using a
potassium gadolinium tungstate Raman-active crystal as a source of narrowband
probe radiation.
AB - Three-color broadband vibrational coherent anti-Stokes Raman scattering (CARS)
temperature measurements were carried out in laminar fuel-rich sooting
ethylene/air flames. Stimulated Raman scattering (SRS) of a picosecond pump laser
pulse in a Raman-active potassium gadolinium tungstate
[KGd(WO4)2] crystal was employed as a source of narrowband
probe radiation. In the three-color CARS experiment, this wavelength-shifted
radiation enables N2-based vibrational CARS temperature measurements
in sooting flames free of the signal interference with the absorption/emission
bands of the flame intermediate radicals C2. Spatial temperature
profiles for different fuel-rich atmospheric pressure ethylene/air flames are
presented in comparison with the results of two-color broadband vibrational and
dual-broadband pure rotational CARS temperature measurements. The comparison
shows the suitability of the three-color CARS measurement technique employing the
KGd(WO4)2 crystal for accurate, C2 interference
free, temperature measurements in sooting flames.
PMID- 28414346
TI - Mixture-fraction measurements with femtosecond-laser electronic-excitation
tagging.
AB - Tracer-free mixture-fraction measurements were demonstrated in a jet using
femtosecond-laser electronic-excitation tagging. Measurements were conducted
across a turbulent jet at several downstream locations both in a pure-nitrogen
jet exiting into an air-nitrogen mixture and in a jet containing an air-nitrogen
mixture exiting into pure nitrogen. The signal was calibrated with known
concentrations of oxygen in nitrogen. The spatial resolution of the measurement
was ~180 MUm. The measurement uncertainty ranged from 5% to 15%, depending on
the mixture fraction and location within the beam, under constant temperature and
pressure conditions. The measurements agree with a mixture fraction of unity
within the potential core of the jet and transition to the self-similar region.
PMID- 28414347
TI - High-resolution Fourier transform measurements of line strengths in the
0002-0000 main isotopologue band of nitrous oxide.
AB - Nitrous oxide (N2O) is a key greenhouse gas and a major ozone
depleting anthropogenic pollutant monitored by the total carbon column observing
network (TCCON) in the 0002-0000-band of its main
isotopologue. Here, we present highly accurate line strengths for this window
determined using Fourier transform infrared spectroscopy with pressure,
temperature, and optical path length being metrologically traceable to the SI.
The obtained results agree with previous studies within the given uncertainties.
Depending on the respective rovibrational transition, the present uncertainties
could be reduced by a factor of 5 to 83 in comparison to literature data.
PMID- 28414348
TI - Optical ray tracing method for simulating beam-steering effects during laser
diagnostics in turbulent media.
AB - In most coherent spectroscopic methods used in gas-phase laser diagnostics,
multiple laser beams are focused and crossed at a specific location in space to
form the probe region. The desired signal is then generated as a result of
nonlinear interactions between the beams in this overlapped region. When such
diagnostic schemes are implemented in practical devices having turbulent reacting
flow fields with refractive index gradients, the resulting beam steering can give
rise to large measurement uncertainties. The objective of this work is to
simulate beam-steering effects arising from pressure and temperature gradients in
gas-phase media using an optical ray tracing approach. The ZEMAX OpticStudio
software package is used to simulate the beam crossing and uncrossing effects in
the presence of pressure and temperature gradients, specifically the conditions
present in high-pressure, high-temperature combustion devices such as gas turbine
engines. Specific cases involving two-beam and three-beam crossing configurations
are simulated. The model formulation, the effects of pressure and temperature
gradients, and the resulting beam-steering effects are analyzed. The results show
that thermal gradients in the range of 300-3000 K have minimal effects, while
pressure gradients in the range of 1-50 atm result in pronounced beam steering
and the resulting signal fluctuations in the geometries investigated. However,
with increasing pressures, the temperature gradients can also have a pronounced
effect on the resultant signal levels.
PMID- 28414349
TI - Second-harmonic generation of a dual-frequency laser in a MgO:PPLN crystal.
AB - A dual-frequency CW laser at a wavelength of 1.064 MUm is frequency doubled in a
MgO:PPLN nonlinear crystal. The fundamental dual-frequency laser has a tunable
beat note from 125 MHz to 175 MHz. A laser-diode pumped fiber amplifier is used
to amplify the dual-frequency fundamental output to a maximum power of 50 W
before frequency doubling. The maximum output power of the green light is 1.75 W
when the input fundamental power is 12 W, corresponding to a frequency doubling
efficiency of 14.6%. After frequency doubling, green light with modulation
frequencies in two bands from 125 MHz to 175 MHz and from 250 MHz to 350 MHz is
achieved simultaneously. The relative intensities of the beat notes at the two
bands can be adjusted by changing the relative intensities at different
frequencies of the fundamental light. The spectral width and frequency
stabilities of the beat notes in fundamental wave and green light are also
measured, respectively. The modulated green light has potential applications in
underwater ranging, communication, and imaging.
PMID- 28414350
TI - Cr:ZnS saturable absorber passively Q-switched mode-locking Tm,Ho:LLF laser.
AB - We first report on a diode-end-pumped passively Q-switched mode-locking Tm,Ho:LLF
laser at 2053 nm by using a Cr:ZnS saturable absorber. A stable Q-switched mode
locking pulse train with a nearly 100% modulation depth was achieved. The
repetition frequency of the Q-switched pulse envelope increased from 0.5 to 12.3
kHz with increasing pump power from 1 to 4.36 W. The maximum average output power
of 145 mW was obtained, and the width of the mode-locked pulse was estimated to
be less than 682 ps with a 250 MHz repetition frequency within a Q-switched pulse
envelope of about 700 ns.
PMID- 28414351
TI - Phase-matching properties of BaGa4Se7 for SHG and SFG in
the 0.901-10.5910 MUm range.
AB - We report new experimental results on the phase-matching properties of a
BaGa4Se7 crystal for harmonic generation of a Nd:YAG laser
pumped AgGaS2 optical parametric oscillator (OPO) and a CO2
laser in the 0.901-10.5910 MUm range. In addition, we present new Sellmeier
equations that provide a good reproduction of the present experimental results as
well as the published data points for a Nd:YAG laser-pumped OPO and an optical
parametric amplifier (OPA) in the 3.10-15.22 MUm range and a Ho:YAG laser-pumped
OPA in the 3.49-5.18 MUm range.
PMID- 28414352
TI - Infrared absorption spectrometer for the determination of temperature and species
profiles in an entrained flow gasifier.
AB - An absorption spectrometer utilizing a tunable distributed feedback diode laser
at 2.3 MUm and an interband cascade laser at 3.1 MUm has been developed to
measure temperature and concentrations of CO, CH4,
C2H2, and H2O under gasification conditions. A
wavelength division multiplexing approach using a single ZrF4-fiber
was used to measure both wavelength regions simultaneously. The performance of
the spectrometer has been tested in laminar flat flames and a heated cell and
then applied for measurements at an atmospheric entrained flow gasifier (REGA). A
water-cooled optical probe was used to provide optical access at two measurement
positions. By moving the burner, axial profiles of temperature and species
concentration could be obtained. These profiles were compared with numerical
simulations and can be used to validate the simulation.
PMID- 28414353
TI - Nonlinear adiabatic optical isolator.
AB - We theoretically propose a method for optical isolation based on adiabatic
nonlinear sum frequency generation in a chirped quasi-phase-matching crystal with
strong absorption at the generated sum frequency wave. The method does not suffer
from the limitations of dynamic reciprocity found in other nonlinear optical
isolation methods and can provide tunable optical isolation with ultrafast all
optical switching capability. Moreover, as an adiabatic technique, it is robust
to variations in the optical design and is relatively broadband.
PMID- 28414354
TI - Dielectric V-ridge gratings: transition from antireflection to retroreflection.
AB - We present a systematic study of the optical properties of dielectric gratings
with symmetric V-shaped ridges having a 90 degree apex angle and refractive index
n. Such structures exhibit completely different optical properties if the
dimensions are scaled with respect to the vacuum wavelength lambda0 of
light. In the subwavelength domain, where the grating period d is less than
lambda0/n, the grating behaves as an antireflection layer. In the
large-period domain d?lambda0 (with normal incidence from the
dielectric side), the grating turns into a micro-retroreflector array. The
transition between these well-known domains is studied using rigorous diffraction
theory. The results are verified experimentally by fabricating and characterizing
V-profile gratings with the aid of wet etching of silicon using a process that
defines a 90 degree apex angle and replication into a polymer.
PMID- 28414355
TI - Experimental study of temporal-spatial binary pattern projection for 3D shape
acquisition.
AB - Three-dimensional (3D) acquisition of an object with modest accuracy and speed is
of particular concern in practice. The performance of digital sinusoidal fringe
pattern projection using an off-the-shelf digital video projector is generally
discounted by the nonlinearity and low switch rate. In this paper, a binary
encoding method to encode one computer-generated standard sinusoidal fringe
pattern is presented for circumventing such deficiencies. In previous work [Opt.
Eng.54, 054108 (2015)OPEGAR0091-328610.1117/1.OE.54.5.054108], we have developed
a 3D system based on this encoding tactic and showed its prospective application.
Here, we first build a physical model to explain the mechanism of how to generate
good sinusoidality. The phase accuracy with respect to the conventional spatial
binary encoding method and sinusoidal fringe pattern is also comparatively
evaluated through simulation and experiments. We also adopt two phase-height
mapping relationships to experimentally compare the measurement accuracy among
them. The results indicate that the proposed binary encoding strategy has a
comparable performance to that of sinusoidal fringe pattern projection and enjoys
advantages over the spatial binary method under the same conditions.
PMID- 28414356
TI - Sensitivity study of x-ray luminescence computed tomography.
AB - X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging
modality that combines the merits of both x-ray imaging (high resolution) and
optical imaging (high sensitivity). In this study, we have evaluated the
sensitivity of XLCT with phantom experiments by scanning targets of different
phosphor concentrations at different depths. We found that XLCT is capable of
imaging targets of very low concentrations (27.6 MUM or 0.01 mg/mL) at
significant depths, such as 21 mm. Our results demonstrate that there is little
variation in the reconstructed target size with a maximum target size error of
4.35% for different imaging depths for XLCT. We have, we believe for the first
time, compared the sensitivity of XLCT with that of traditional computed
tomography (CT) for phosphor targets. We found that XLCT's use of x-ray-induced
photons provides much higher measurement sensitivity and contrast compared to CT,
which provides image contrast solely based on x-ray attenuation.
PMID- 28414357
TI - Infrared Brewster-angle polarizing beam splitter using a high-index prism with a
small wedge angle.
AB - Specular reflection at the Brewster angle by a planar surface of a high
refractive-index transparent substrate is an effective means of generating
linearly polarized light in the infrared. However, in such a reflection linear
polarizer, the refracted light beam is usually dumped. In this paper we describe
a polarizing beam splitter (PBS) that uses a high-index prism with a small wedge
angle to generate two orthogonally p and s linearly polarized beams that travel
in orthogonal directions. A single-layer antireflection coating (ARC) at the exit
face of the prism can be embedded with aligned Ag nano needles to suppress the
transmission of the small, residual, s-polarized refracted component. An example
of such PBS that uses a PbTe prism with ZnSe ARC in the mid-infrared is
presented.
PMID- 28414358
TI - Optimizing spectral compositions of multichannel LED light sources by IES color
fidelity index and luminous efficacy of radiation: publisher's note.
AB - This note points out additional funding information that was not added to Appl.
Opt.56, 1962 (2017).APOPAI1559-128X10.1364/AO.56.001962.
PMID- 28414359
TI - Optical coherence tomography-integrated, wearable (backpack-type), compact
diagnostic imaging modality for in situ leaf quality assessment: publisher's
note.
AB - This note points out additional funding that was not added to Appl. Opt.56, D108
(2017)APOPAI0003-693510.1364/AO.56.00D108.
PMID- 28414360
TI - Visualizing spatiotemporal pulse propagation: first-order spatiotemporal
couplings in laser pulses.
AB - Even though a general theory of first-order spatiotemporal couplings exists in
the literature, it is often difficult to visualize how these distortions affect
laser pulses. In particular, it is difficult to show the spatiotemporal phase of
pulses in a meaningful way. Here, we propose a general solution to plotting the
electric fields of pulses in three-dimensional space that intuitively shows the
effects of spatiotemporal phases. The temporal phase information is color-coded
using spectrograms and color response functions, and the beam is propagated to
show the spatial phase evolution. Using this plotting technique, we generate two-
and three-dimensional images and movies that show the effects of spatiotemporal
couplings.
PMID- 28414361
TI - Nonimaging polygonal mirrors achieving uniform irradiance distributions on
concentrating photovoltaic cells.
AB - We introduce a design methodology for nonimaging, single-reflection mirrors with
polygonal inlet apertures that generate a uniform irradiance distribution on a
polygonal outlet aperture, enabling a multitude of applications within the domain
of concentrated photovoltaics. Notably, we present single-mirror concentrators of
square and hexagonal perimeter that achieve very high irradiance uniformity on a
square receiver at concentrations ranging from 100 to 1000 suns. These optical
designs can be assembled in compound concentrators with maximized active area
fraction by leveraging tessellation. More advanced multi-mirror concentrators,
where each mirror individually illuminates the whole area of the receiver, allow
for improved performance while permitting greater flexibility for the
concentrator shape and robustness against partial shading of the inlet aperture.
PMID- 28414362
TI - Wideband and multi-frequency infrared cloaking of spherical objects by using the
graphene-based metasurface.
AB - The ultrathin graphene metasurface is proposed as a mantle cloak to achieve
wideband tunable scattering reduction around the spherical (three-dimensional)
objects. The cloaking shell over the metallic or dielectric sphere is structured
by a periodic array of graphene nanodisks that operate at infrared frequencies.
By using the polarizability of the graphene nanodisks and equivalent conductivity
method, the metasurface reactance is obtained. To achieve the cloaking shell for
both dielectric and conducting spheres, the metasurface reactance as a function
of nanodisks dimensions, graphene's Fermi energy, and permittivity of the
surrounding areas can be tuned from the inductive to capacitive situation.
Inhomogeneous metasurfaces including graphene nanodisks with different radii
provide wideband invisibility due to extra resonances. We could significantly
increase the 3-dB bandwidth more than the homogenous case by simpler realistic
designs compared to the multi-layer structures. The analytical results are
confirmed with full-wave numerical simulations.
PMID- 28414363
TI - Signal restoration method for restraining the range walk error of Geiger-mode
avalanche photodiode lidar in acquiring a merged three-dimensional image.
AB - The fluctuation in the number of signal photoelectrons will cause a range walk
error in a Geiger-mode avalanche photodiode (Gm-APD) lidar, which significantly
depends on the target intensity. For a nanosecond-pulsed laser, the range walk
error of traditional time-of-flight will cause deterioration. A new signal
restoration method, based on the Poisson probability response model and the
center-of-mass algorithm, is proposed to restrain the range walk error. We obtain
a high-precision depth and intensity merged 3D image using this method. The range
accuracy is 0.6 cm, and the intensity error is less than 3%.
PMID- 28414364
TI - Experimental analysis of stress fields of rotating structural elements by means
of reflection photoelasticity.
AB - The subject of this paper is an experimental stress analysis of a rotor with a
symmetrical arm end and a rotor with an asymmetrical arm end. The main aim of
this paper is to test the application of the Harmonic Star Method software
developed by the authors. This software analyzes stress states in rotating
structural elements. The stress state of the analyzed rotors is caused by
centrifugal forces. The experiment was carried out by means of reflection
photoelasticity, and the experimental solution was focused on periodical dynamic
effects, which required the use of stroboscopic white light. The resulting
principal normal stresses were compared with stress values, which were obtained
by analytical calculations and by numerical means of the finite element method.
PMID- 28414365
TI - Random phase-shifting algorithm by constructing orthogonal phase-shifting fringe
patterns.
AB - The intensity distribution of fringe patterns becomes nonsinusoidal in real
testing environments. Thus, the performance of existing phase shift extraction
algorithms, which usually compute the desired phase shift by arccosine function
or arcsine function, may be affected. In the presented paper, we report an
arctangent-function-based technique to solve this disturbance. First, two
orthogonal fringe patterns are constructed through subtraction and addition of
two background-removed images. Second, the unequal amplitude between two new
fringe patterns is eliminated using a normalization process. Third, the phase
shift is determined by computing the norms of the two new images. The proposed
method is fast and can be implemented easily in many applications. We verify the
algorithm performance and robustness using both simulated and experimental data,
indicating the high accuracy of the presented method.
PMID- 28414366
TI - Nonlinearity characterization of array spectroradiometers for the solar UV
measurements.
AB - Array spectroradiometers are attractive alternatives to scanning
spectroradiometers in solar ultraviolet measurements. However, the measurement of
solar spectral irradiance imposes stringent requirements for the linearity of the
instruments. In this article, two array spectroradiometers were characterized for
nonlinearity. Significant nonlinearities, in excess of 10%, as a function of
analog-to-digital converter counts were discovered. Additional nonlinearities as
a function of integration time were observed at very long integration times. No
clear residual nonlinearity as a function of spectral irradiance was witnessed
despite the characterization spanning four orders of magnitude of spectral
irradiance. The characterizations were carried out with three measurement setups
that are briefly compared.
PMID- 28414367
TI - Integrated refractive index sensor using silicon slot waveguides.
AB - We propose an integrated refractive index (RI) sensor based on evanescent field
absorption (EFA) within a silicon slot waveguide, where the RI variation is
translated into a varied attenuation coefficient and eventually the output power
at the end of the waveguide. To demonstrate the operating principle of such a RI
EFA sensor, a specific structure is designed and discussed with numerical
simulations. The calculated results indicate that the detection limit of our
proposed RI-EFA sensor could be as good as ~10-8 RIU for homogeneous
sensing and ~10-7 RIU for surface sensing with optimized structural
parameters at a wavelength of 1064 nm. Since only a straight slot waveguide and
optical power detection are required for our proposed sensor, we believe that it
is promising to achieve an integrated and portable sensor on a single chip.
PMID- 28414368
TI - Tunable femtosecond near-IR source by pumping an OPA directly with a 90 MHz
Yb:fiber source.
AB - Up to 400 mW of near-IR (1370-1500 nm) femtosecond pulses are generated from an
optical parametric amplifier directly driven by a Yb:fiber oscillator delivering
100 fs pulses at 1036 nm. The process is seeded by a stable supercontinuum
obtained from a photonic crystal fiber. We use a single pass through a 3 mm,
magnesium oxide-doped, periodically poled LiNbO3 downconversion
crystal to produce a near-IR pulse train with a remarkable power stability of
1.4% (RMS) during one hour. Tuning is achieved by the temperature and the poling
period of the nonlinear crystal.
PMID- 28414369
TI - Frequency comb calibrated frequency-sweeping interferometry for absolute group
refractive index measurement of air.
AB - The absolute group refractive index of air at 194061.02 GHz is measured in real
time using frequency-sweeping interferometry calibrated by an optical frequency
comb. The group refractive index of air is calculated from the calibration peaks
of the laser frequency variation and the interference signal of the two beams
passing through the inner and outer regions of a vacuum cell when the frequency
of a tunable external cavity diode laser is scanned. We continuously measure the
refractive index of air for 2 h, which shows that the difference between measured
results and Ciddor's equation is less than 9.6*10-8, and the standard
deviation of that difference is 5.9*10-8. The relative uncertainty of
the measured refractive index of air is estimated to be 8.6*10-8. The
data update rate is 0.2 Hz, making it applicable under conditions in which air
refractive index fluctuates fast.
PMID- 28414370
TI - Semi-automated localization of dermal epidermal junction in optical coherence
tomography images of skin.
AB - Identifying the location of the dermal epidermal junction (DEJ) in skin images is
essential in several clinical applications of dermatology such as epidermal
thickness determination in healthy versus unhealthy skins, such as basal cell
carcinoma. Optical coherence tomography (OCT) facilitates the visual detection of
DEJ in vivo. However, due to the granular texture of speckle and a low contrast
between dermis and epidermis, a skin border detection method is required for DEJ
localization. Current DEJ algorithms work well for skins with a visible
differentiable epidermal layer but not for the skins of different body sites. In
this paper, we present a semi-automated DEJ localization algorithm based on graph
theory for OCT images of skin. The proposed algorithm is performed in an
interactive framework by a graphical representation of an attenuation coefficient
map through a uniform-cost search method. For border thinning, a fuzzy-based
nonlinear smoothing technique is used. For evaluation, the DEJ detection method
is used by several experts, and the results are compared with manual
segmentation. The mean thickness error between the proposed algorithm and the
experts' opinion in the Bland-Altman plot is computed as 14 MUm; this is
comparable to the resolution of the OCT. The results suggest that the proposed
image processing method successfully detects DEJ.
PMID- 28414371
TI - Flexible global calibration of multiple cameras with nonoverlapping fields of
view using circular targets.
AB - Global calibration of multicamera systems is a difficult problem. The key is to
find an appropriate calibration target. This paper proposes a flexible method to
construct a global calibration target with circular targets. Any object that is
to be measured by the system can be used as a calibration target with the help of
a hand-held scanner. The calibration method does not need a special calibration
target or multiple shots, which makes it flexible in applications. Circular
targets pasted on the calibration target are used as features that are captured
by cameras. The particle swarm optimization method is employed to correct the
eccentricity error in the projection of circular targets. The eccentricity
correction method does not need any prior knowledge except the cameras' intrinsic
parameters. A synthetic data experiment was performed to validate the
eccentricity correction method, and a physical experiment in a train wheelset
inner-side distance measurement system was performed to validate the global
calibration method. The measurement accuracy of the system was better than 0.1
mm, and the eccentricity correction method improved the three-dimensional
reconstruction accuracy by about 0.1 mm.
PMID- 28414372
TI - Graphene-based near-field optical microscopy: high-resolution imaging using
reconfigurable gratings.
AB - High-resolution and fast-paced optical microscopy is a requirement for current
trends in biotechnology and materials industry. The most reliable and adaptable
technique so far to obtain higher resolution than conventional microscopy is near
field scanning optical microscopy (NSOM), which suffers from a slow-paced nature.
Stemming from the principles of diffraction imaging, we present fast-paced
graphene-based scanning-free wide-field optical microscopy that provides image
resolution that competes with NSOM. Instead of spatial scanning of a sharp tip,
we utilize the active reconfigurable nature of graphene's surface conductivity to
vary the diffraction properties of a planar digitized atomically thin graphene
sheet placed in the near field of an object. Scattered light through various
realizations of gratings is collected at the far-field distance and postprocessed
using a transmission function of surface gratings developed on the principles of
rigorous coupled wave analysis. We demonstrate image resolutions of the order of
lambda0/16 using computational measurements through binary graphene
gratings and numerical postprocessing. We also present an optimization scheme
based on the genetic algorithm to predesign the unit cell structure of the
gratings to minimize the complexity of postprocessing methods. We present and
compare the imaging performance and noise tolerance of both grating types. While
the results presented in this article are at terahertz frequencies
(lambda0=10 MUm), where graphene is highly plasmonic, the proposed
microscopy principle can be readily extended to any frequency regime subject to
the availability of tunable materials.
PMID- 28414373
TI - Superlensing microscope objective lens.
AB - Conventional microscope objective lenses are diffraction limited; they cannot
resolve subdiffraction features of a size smaller than 250-300 nm under white
lighting condition. New innovations are required to overcome this limitation. In
this paper, we propose and demonstrate a new superlensing objective lens that
possesses a resolution of 100 nm, which is a two-times resolution improvement
over conventional objectives. This is accomplished by integrating a conventional
microscope objective lens with a superlensing microsphere lens using a customized
lens adaptor. The new objective lens was successfully demonstrated for label-free
super-resolution imaging of 100 nm features in engineering and biological
samples, including a Blu-ray disk sample and adenoviruses. Our work opens a new
door to develop a generic optical superlens, which may transform the field of
optical microscopy and imaging.
PMID- 28414374
TI - Practical dual-band terahertz imaging system.
AB - This paper introduces a dual-band terahertz imaging system as a potential product
for nondestructive testing using heterodyne detectors and continuous-wave
sources. The operating frequencies of the system are 110.4 and 220.8 GHz.
Multiband fusion technology combines the advantages of the greater spatial
resolution of the high-frequency band and the enhanced sensitivity of the low
frequency band to improve the detection ability of the system. Additionally, the
interference cancellation technology is used to obtain a superior image quality.
The spatial resolution of this system was approximately 3 mm. The results show
that the system can be used for bonding quality and embedded defect detection in
radomes and foam materials adhered to metal plates in aircrafts.
PMID- 28414375
TI - Evaluation of femtosecond laser damage to gold pulse compression gratings
fabricated by magnetron sputtering and e-beam evaporation.
AB - In this study, two kinds of Au-coated gratings (ACGs) with a period of 1740
lines/mm were fabricated and evaluated. For these ACG samples, magnetron
sputtering and e-beam evaporation were used as the gold deposition process, and
the samples had a bandwidth of at least 170 nm, with the -1st-order diffraction
efficiency exceeding 90% around the center wavelength of 800 nm. The one-on-one
damage threshold of ACGs fabricated by magnetron sputtering and e-beam
evaporation measured at a pulse width of 60 fs was 0.59 J/cm2 and
0.43 J/cm2 in the case of the beam normal fluence, respectively. The
typical damage morphology of the former type of samples was melting of the gold
film, whereas those of the latter type were blisters and peeling off of the gold
film. In theory, the electromagnetic field, temperature field, and thermal stress
field distribution in the ACGs were calculated using the finite element method.
We demonstrated that the adhesion between the gold film and the photoresist
played an important role in determining the damage behavior. Thus, the laser
resistance of ACG can be improved by enhancing the adhesion between the gold film
and the photoresist, and magnetron sputtering was an alternative method to obtain
ACGs with much better adhesion.
PMID- 28414376
TI - Electromagnetic optimization of the integrated magnetorheological jet polishing
tool and its application in millimeter-scale discontinuous structure processing.
AB - To meet the special demands in small-scale discontinuous optical surface
fabrication, the integrated magnetorheological jet polishing (IMJP) tool with
multiple motion degrees is introduced in this paper. Four jetting models are
implemented and investigated by means of the IMJP tool for practical manufacture.
To ensure steady jetting in a long distance, ideal distribution characteristics
of the magnetic field in the structure is proposed, based on electromagnetic
theory. The magnetic field distribution is simulated subsequently using the
finite element analysis method, and three key parameters in the IMJP tool
structure are optimized through the simulations. The actual magnetic flux density
is measured and spot polishing experiments are conducted in different standoff
distances, verifying the effectiveness of the optimization. A processing
experiment of a millimeter scale structure with milling tool marks located on a
surface with nonuniform curvatures was conducted using the IMJP tool. The
roughness of the polishing region converged to 4.86 nm Ra from a low initial
quality after processing, and the tool marks have been efficiently removed. The
experimental results reveal the reliability of the setup design and the
remarkable roughness convergence ability of the IMJP tool for small complex
structures.
PMID- 28414377
TI - Polarization-based spatial filtering for directional and nondirectional edge
enhancement using an S-waveplate.
AB - Using polarization as an additional parameter apart from amplitude and phase in
spatial filtering experiments offers additional advantages and possibilities. An
S-waveplate that can convert a linearly polarized light into radially or
azimuthally polarized light can also be used for isotropic edge enhancement. For
anisotropic edge enhancement, introduction of a polarizer at the output was
recommended and edge selection was done by orientation of the polarizer. But the
full potential of the S-waveplate as a spatial filter has not been exploited so
far. Unlike the standard amplitude and phase-based Fourier filters, which are
independent to the state of polarization of the illuminating beam, the S
waveplate acts in a different way depending on the state of polarization. The
edge selection does not need to be carried out by changing the orientation of the
polarizer. With a fixed polarizer at the output, we show that either isotropic or
anisotropic edge enhancement in any desired orientation can be performed by
operating the same spatial filter setup in different illuminating polarization
states.
PMID- 28414378
TI - Interference filter tilting to detect a polycyclic aromatic hydrocarbon at the
second harmonic of wavelength modulation frequency.
AB - We present a practical implementation of the wavelength-modulation spectroscopy
technique with second-harmonic detection for selective detection and
concentration measurements of polycyclic aromatic hydrocarbons (PAHs)-common
fossil fuel pollutants. The method is based on excitation light wavelength
modulation around the maximum of a narrow peak in the absorption spectrum of a
PAH and lock-in detection of fluorescence at the second harmonic of the
excitation wavelength modulation frequency. A violet LED is used as the
excitation source and wavelength modulation is performed via narrowband
interference filter tilting. Feasibility is demonstrated with a carcinogenic PAH,
benzo(k)fluoranthene. Model computations are presented to estimate the influence
of the background signal on the sensitivity of the method.
PMID- 28414379
TI - Efficient acousto-optic crystal, TlInS2: acoustic and elastic
anisotropy.
AB - We have studied experimentally the acoustic wave velocities for TlInS2
crystals and determined all components of their elastic stiffness and compliance
tensors. It has been found that TlInS2 reveals small elastic
anisotropy with respect to normal mechanical stresses. The compliance components
S44 and S55 are very large, thus suggesting that the
TlInS2 crystals are extremely compliant to the shear stresses in the
cleavage plane. We have also revealed that the velocities of some of the quasi
transverse waves are very low (~725 m/s), leading to extremely high acousto
optic figures of merit (~2200-9000*10-15 s3/kg). This
implies that the crystals under study can prove to be a very efficient acousto
optic material.
PMID- 28414380
TI - Iterative reconstruction of scene depth with fidelity based on light field data.
AB - Depth reconstruction from the light field, as a depth extracting approach, is a
vibrant research field in computational imaging. In this paper, depth
reconstruction from the light field was approached as an optimization problem by
analyzing the forward and inverse models. The forward and inverse models present
the connection between the light field and the depth of the scene. We proposed an
iterative method for scene depth reconstruction with fidelity from 4D light field
data. The objective function of the optimization problem entails three terms, of
which the matching term is used as the fidelity term, while the gradient term and
classification term constitute the penalty terms. The iterative method minimized
the objective function by correcting mismatching pixels iteratively. In this way,
the reconstruction accuracy of the scene depth was significantly improved with
high robustness, especially in the weak texture and occlusion regions. The
experimental results show that the depth map can be reconstructed with high
accuracy by the iterative method, in alignment with high depth resolution in the
weak texture and occlusion regions. An accurate 3D surface in the field of view
can be achieved using the depth information reconstructed from the 4D light
field.
PMID- 28414381
TI - Interaction between a bubble and a metal target for underwater laser propulsion.
AB - Optical beam deflection and high-speed photographic methods are employed to
investigate the interaction mechanism between a laser-induced bubble and a metal
target for underwater laser propulsion. A preliminary theory is proposed to
reveal the step increases of the kinetic energy transferred to the target during
the process of increasing the incident laser energy. This theory also helps to
explain the increasing coupling efficiency with incident laser energy for
underwater laser propulsion.
PMID- 28414382
TI - Real-time polarization imaging algorithm for camera-based polarization navigation
sensors.
AB - Biologically inspired polarization navigation is a promising approach due to its
autonomous nature, high precision, and robustness. Many researchers have built
point source-based and camera-based polarization navigation prototypes in recent
years. Camera-based prototypes can benefit from their high spatial resolution but
incur a heavy computation load. The pattern recognition algorithm in most
polarization imaging algorithms involves several nonlinear calculations that
impose a significant computation burden. In this paper, the polarization imaging
and pattern recognition algorithms are optimized through reduction to several
linear calculations by exploiting the orthogonality of the Stokes parameters
without affecting precision according to the features of the solar meridian and
the patterns of the polarized skylight. The algorithm contains a pattern
recognition algorithm with a Hough transform as well as orientation measurement
algorithms. The algorithm was loaded and run on a digital signal processing
system to test its computational complexity. The test showed that the running
time decreased to several tens of milliseconds from several thousand
milliseconds. Through simulations and experiments, it was found that the
algorithm can measure orientation without reducing precision. It can hence
satisfy the practical demands of low computational load and high precision for
use in embedded systems.
PMID- 28414383
TI - Design and simulation of reflect-array metasurfaces in the visible regime.
AB - Metasurfaces are new, promising ultrathin materials that can enable many novel
optical devices due to their ability to act as a discontinuity interface that
introduces an abrupt change in amplitude, phase, and sometimes the polarization
of the incident light at the wavelength scale. Therefore they can function as
flat optical elements. Here, we investigate the anomalous reflection of light for
transverse-magnetic (TM) polarization for normal and oblique incidence in the
visible regime. We propose gradient phase gap-surface plasmon metasurfaces that
exhibit high conversion efficiency (up to ~97% of total reflected light) to the
anomalous reflection angle for blue, green, and red wavelengths at normal and
oblique incidence, and where light polarization is unchanged after the
reflection.
PMID- 28414384
TI - Measurement of the linear thermo-optical coefficient of
Ga0.51In0.49P using photonic crystal nanocavities.
AB - Ga0.51In0.49P is a promising candidate for thermally
tunable nanophotonic devices due to its low thermal conductivity. In this work we
study its thermo-optical response. We obtain the linear thermo-optical
coefficient dn/dT=2.0+/-0.3.10-4 K-1 by investigating the
transmission properties of a single mode-gap photonic crystal nanocavity.
PMID- 28414385
TI - Common-path digital holographic microscopy for near-field phase imaging based on
surface plasmon resonance.
AB - We develop a common-path digital holographic microscopy based on prism-coupling
surface plasmon resonance (SPR) for near-field phase imaging. A single beam
splitter with specific configuration is introduced in an SPR imaging system to
realize off-axis holographic recording. By measuring the phase shift difference
of the reflected light at SPR exploiting the proposed holographic microscopy with
high temporal stability, near-field characteristic measurement can be realized.
With its simplicity, vibration isolation, and inherent capability of phase
curvature compensation, the recommended system shows advanced performance in
monitoring tiny refractive index variations and imaging biological tissues.
PMID- 28414386
TI - Detecting phase transitions in a CaCl2-H2O system at low
temperatures using a fiber-optic Fresnel reflection sensor.
AB - Temperature-induced crystallization events in an aqueous calcium chloride
solution in the concentration range of 15-40 mass% are monitored using an optical
fiber Fresnel reflection sensor in the temperature range of 30 degrees C to -200
degrees C. The deviation of the phase boundary from equilibrium and the formation
of an eutectic mixture followed by its densification during rapid cooling are
inferred from the distinct signatures of the optical fiber sensor via the changes
in refractive index. During the natural heating at laboratory ambient conditions,
the optical signals impart the completion of dissolution of ice and
CaCl2.6H2O. The corresponding temperatures have been used
in Linke's equations to obtain the salinities, which are in good agreement with
the intended solution concentrations. The sensor signal imparts simultaneous
melting of the constituents of the eutectic mixture of a 29.7 mass% solution
during the natural heating phase. The persistence of the metastable liquid phase
at -200 degrees C for tens of minutes followed by solidification is observed at
all the concentrations studied. Finally, the feasibility of monitoring phase
transitions in a NaCl-CaCl2-H2O system has been
demonstrated.
PMID- 28414387
TI - Multi-point temperature sensing using a linear-cavity lasing system.
AB - A multi-point fiber sensing system formed from a linear cavity laser is proposed.
Various optical sensing systems have been investigated, for example, using fiber
Bragg grating (FBG) and Brillouin scattering for multi-point sensing. This paper
focuses on a simple sensing system by using multi-wavelength lasing with parallel
cavities and a semiconductor optical amplifier (SOA). First, optical nonlinearity
in amplification of the SOA is discussed to clarify the effects of gain
saturation and four-wave mixing on the proposed multi-channel sensing system. And
then lasing conditions in the linear cavity laser consisting of an SOA, an
arrayed waveguide grating (AWG), and FBGs are theoretically investigated. The
multi-wavelength lasing power is found to be limited mainly by gain saturation in
the SOA. The lasing power for the eight-channel system is evaluated to be -8.5
dBm when the total loss in the linear cavity is 10 dB. The lasing power can be
increased by 3 dB when the channel number is decreased to four. Next, multi
wavelength lasing in the cavity consisting of an SOA, an AWG, a loop mirror, and
fiber mirror reflectors is experimentally demonstrated up to eight channels.
Finally, two-channel temperature sensing ranging from 13 degrees C to 76 degrees
C is experimentally confirmed by using two FBGs as the sensing elements with an
AWG having 100-GHz bandwidth.
PMID- 28414388
TI - Infrared spectroscopy of secondary organic aerosol precursors and investigation
of the hygroscopicity of SOA formed from the OH reaction with guaiacol and
syringol.
AB - Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR)
synchrotron analyses supplemented by density functional theory (DFT) anharmonic
calculations have been undertaken to study the fundamental vibrational signatures
of guaiacol and syringol, two methoxyphenol compounds found at the highest
concentrations in fresh wood smoke and precursors of secondary organic aerosols
(SOA) affecting the radiative balance and chemistry of the atmosphere.
Nitroderivatives of these two compounds have also been studied experimentally for
nitroguaiacol and theoretically for nitrosyringol. All the active fundamental
vibrational bands have been assigned and compared to available gas phase
measurements, providing a vibrational database of the main precursors for the
analysis of SOA produced by atmospheric oxidation of methoxyphenols. In addition,
the SOA formed in an atmospheric simulation chamber from the OH reaction with
guaiacol and syringol were analyzed using the ATR-FTIR synchrotron spectroscopy
and their hygroscopic properties were also investigated. The vibrational study
confirms that nitroguaiacol and nitrosyringol are the main oxidation products of
methoxyphenols by OH and are key intermediates in SOA production. The hydration
experiments highlight the hydrophilic and hydrophobic characters of nitrosyringol
and nitroguaiacol, respectively.
PMID- 28414389
TI - Laser applications to chemical, security, and environmental analysis:
introduction to the feature issue.
AB - This Applied Optics feature issue on laser applications to chemical, security,
and environmental analysis (LACSEA) highlights papers presented at the LACSEA
2016 Fifteenth Topical Meeting sponsored by the Optical Society of America.
PMID- 28414390
TI - Therapeutic monitoring of amiodarone: pharmacokinetics and evaluation of the
relationship between effect and dose/concentration.
AB - Amiodarone is the most effective agent in the therapy of arrhythmias. However,
the clinical effect of acute and chronic treatment is unclear and there are
differences irrespective of comparable plasma/myocardial amiodarone and its
metabolite desethylamiodarone concentations as well. Its unusual pharmacokinetics
results in interindividual variation in plasma levels. The association between
amiodarone and desethylamiodarone plasma levels and clinical efficacy is
difficult to evaluate. This review was carried out to assess whether there is any
objective correlation between amiodarone and desethylamiodarone plasma levels and
the clinical effect. We summarized the results of relevant studies and clarified
the relationship between plasma levels and effect vis a vis the pharmacokinetics
and pharmacogenetics of this drug. Certain correlation was seen with oral
amiodarone therapy, in others, plasma amiodarone levels were unrelated to
therapeutic response and showed no correlation with changes in electrocardiogram
or electrophysiological parametres. Several studies show that plasma
concentration ranging between 0.5 and 2.5 mg/L appears to be the most effective,
others demonstrate no difference between responders and non-responders. One way
of interpreting plasma levels is to establish an individual patient's effective
concentration. Therapeutic drug monitoring can contribute to determining optimal
concentration.
PMID- 28414392
TI - Firearm Injury Prevention: The Role of the Clinician.
AB - More than 2,500 people younger than age 20 years die due to a firearm injury
annually in the United States, and thousands more suffer injuries that are
nonfatal. With nearly one firearm for every American in the US, exposure to a gun
at some point during childhood or adolescence is highly likely. The high number
of fatalities caused by firearms emphasizes the importance of primary prevention.
This article calls on pediatricians to use their advantage as child development
experts to discuss firearm injury prevention in clinical practice via a pragmatic
and nonjudgmental approach. [Pediatr Ann. 2017;46(4):e127-e130.].
PMID- 28414393
TI - Neurological Disorders in Primary Care Pediatrics.
PMID- 28414394
TI - Overview of Sleep and Sleep Disorders in Infancy and Childhood.
AB - Sleep in children is an important and dynamic process, affecting numerous aspects
of health and development. Problems with sleep are relatively common but often
can be challenging to recognize. This article reviews the fundamental aspects of
sleep in children from infancy to adolescence, and the most common and relevant
sleep disorders likely to be encountered in a general pediatric practice. Where
available, current evidence-based recommendations for management are discussed,
including indications for referral to a sleep specialist. [Pediatr Ann.
2017;46(4):e133-e138.].
PMID- 28414395
TI - The Role of Active Recovery and "Rest" After Concussion.
AB - For several years both cognitive and physical rest remained at the forefront in
pediatric postconcussion management. However, the concept of "rest" has not been
well defined and there remains significant variability both in terms of rest
recommendations provided as well as adherence to such recommendations. More
recently, there has been growing evidence to suggest that an earlier return to
light or moderate activity is not detrimental and may, in fact, facilitate
symptomatic improvement, thereby highlighting a new role for active
rehabilitation in recovery from concussion. In this article, we compare historic
recommendations for rest with emerging strategies focused on active
rehabilitation. [Pediatr Ann. 2017;46(4):e139-e144.].
PMID- 28414396
TI - Postural Tachycardia Syndrome: Diagnosis and Management in Adolescents and Young
Adults.
AB - Postural tachycardia syndrome (POTS) represents a common form of orthostatic
intolerance that disproportionately affects young women from puberty through
adulthood. Patients with POTS have day-to-day orthostatic symptoms with the
hallmark feature of an excessive, sustained, and symptomatic rise in heart rate
during orthostatic testing. Although considerable overlap exists, three subtypes
of POTS have been described: neuropathic, hyperadrenergic, and hypovolemic forms.
The wide spectrum of symptoms and comorbidities can make treatment particularly
challenging. Volume expansion with fluid and salt, exercise, and education
constitute a reasonable initial therapy for most patients. Several medicines are
also available to treat orthostatic intolerance and the associated comorbidities.
Defining the POTS subtypes clinically in each patient may help to guide medicine
choices. A multidisciplinary approach to overall management of the patient with
POTS is advised. This review highlights several aspects of POTS with a specific
focus on adolescent and young adult patients. [Pediatr Ann. 2017;46(4):e145
e154.].
PMID- 28414397
TI - Childhood Headache: A Brief Review.
AB - Headaches are common in childhood and adolescence and can cause significant
distress and disability for a child and their family. Providers need to be able
to identify "red flags" for worrisome causes of secondary headaches and recognize
typical primary headache characteristics to provide each patient with the best
possible care to improve their quality of life and minimize disability. This
article reviews the epidemiology of headaches in children, signs and symptoms of
secondary headaches, definitions of some primary childhood headaches, and options
for management of both acute and chronic pediatric migraine. [Pediatr Ann.
2017;46(4):e155-e165.].
PMID- 28414398
TI - Tuberous Sclerosis Complex: A Review.
AB - Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present at
any age and can affect multiple organ systems. This disorder is usually
identified in infants and children based on characteristic skin lesions,
seizures, and cellular overgrowth or hamartomas in the heart, brain, and kidneys.
Tuberous sclerosis complex is a genetic disorder caused by a mutation in either
the TSC1 or TSC2 gene leading to dysfunction of hamartin or tuberin,
respectively. Hamartin and tuberin form a protein complex that helps regulate
cellular hyperplasia. Accurate diagnosis is essential in implementing appropriate
surveillance and treatment to patients with this disorder. Specific guidelines
for diagnosis, surveillance, and management have been proposed by the
International Tuberous Sclerosis Complex Consensus Group. Treatment of tuberous
sclerosis complex is in part symptomatic; however, for certain clinical
manifestations, specific treatments may be indicated. [Pediatr Ann.
2017;46(4):e166-e171.].
PMID- 28414399
TI - Current Understanding of the Health Effects of Electromagnetic Fields.
AB - There has been an exponential increase in the use of electronic devices over the
past few decades. This has led to increased exposure to electromagnetic fields
(EMF). Electric fields result from differences in voltage, whereas magnetic
fields result from the flow of electric current. Higher-frequency waves of EMF
have more energy than lower-frequency waves, and thus generally tend to be more
harmful. An EMF activates cellular stress response and also causes breaks in DNA
strands. There are many methodological barriers to effectively measuring the
associations of EMF and childhood cancers. The consensus from multiple studies is
that there is no causal role of extremely low-frequency EMFs in childhood
cancers, including brain cancer. A recent study showed a link between EMF
radiation and the development of malignant tumors in rats. In light of that
study, the American Academy of Pediatrics set out new recommendations to decrease
the adverse effects of cellphone exposure on children. [Pediatr Ann.
2017;46(4):e172-e174.].
PMID- 28414400
TI - Happy Birthday STFM.
PMID- 28414401
TI - STFM - Two Histories.
PMID- 28414402
TI - Perspectives of an Early Adopter of Family Medicine as a Discipline and a Cause.
PMID- 28414403
TI - STFM - 50 Years of Working to Transform Health Care Through Education.
PMID- 28414404
TI - This Is Why.
PMID- 28414405
TI - A Creation Story.
PMID- 28414406
TI - Residency Training in Family Medicine: A History of Innovation and Program
Support.
AB - BACKGROUND: Residency programs have been integral to the development, expansion
and progression of family medicine as a discipline. Three reports formed the
foundation for graduate medical education in family medicine: Meeting the
Challenge of Family Practice, The Graduate Education of Physicians, and Health is
a Community Affair. In addition, the original core concepts of comprehensiveness,
coordination, continuity, and patient centeredness continue to serve as the
foundation for residency training in family medicine. While the Residency Review
Committee for Family Medicine of the Accreditation Council for Graduate Medical
Education has provided the requirements for training throughout the years, key
organizations including the Society of Teachers of Family Medicine, the American
Academy of Family Physicians, the Association of Family Medicine Residency
Directors, and the American Board of Family Medicine have provided resources for
and supported innovation in programs. Residency Program Solutions, National
Institute for Program Director Development, and Family Medicine Residency
Curriculum Resource are several of the resources developed by these
organizations. The future of family medicine residency training should continue
the emphasis on innovation and development of resources to enhance the training
of residents. Areas for further development include leadership and health care
systems training that allows residents to assume leadership of multidisciplinary
health care teams and increase focus on the family medicine practice population
as the main unit for resident education.
PMID- 28414407
TI - Medical Student Teaching and Recruiting: 50 Years of Balancing Two Educational
Aims.
AB - BACKGROUND: Family medicine (FM) undergraduate medical educators have had two
distinct missions, to increase the knowledge, skills, and attitudes of all
students while also striving to attract students to the field of family medicine.
A five decade literature search was conducted gathering FM curricular innovations
and the parallel trends in FM medical student interest. Student interest in FM
had a rapid first-decade rise to 14%, a second 1990's surge, followed by a drop
to the current plateau of 8-9%. This falls far short of the 30-50% generalist
benchmark needed to fill the country's health care needs. Curricular innovations
fall into three periods: Charismatic Leaders & Clinical Exposures (1965-1978),
Creation of Clerkships of FM (1979-1998) and Curricular Innovations (1998
present). There is good evidence that having a required third-year clerkship
positively impacts student interest in the field, however there is little
research regarding the recruitment impact of specific clerkship curricula. Other
tools associated with student interest include programming geared towards primary
care or rural training and extracurricular opportunities such as FM Interest
Groups. Strategic plans to improve the primary care work force should focus
funding and legislative efforts on effective methods such as: establishing and
maintaining FM clerkships, admitting students with rural and underserved
backgrounds or primary care interest, developing longitudinal primary care
tracks, and supporting extracurricular FM activities. Rigorous research is needed
to assess how best to utilize limited educational resources to ensure that all
students graduate with a core set of FM competence as well as an increased FM
matriculation. Strategic plans to improve the primary care work force should
focus funding and legislative efforts on effective methods such as: establishing
and maintaining FM clerkships, admitting students with rural and underserved
backgrounds or primary care interest, developing longitudinal primary care
tracks, and supporting extracurricular FM activities. Rigorous research is needed
to assess how best to utilize limited educational resources to ensure that all
students graduate with a core set of FM competence as well as an increased FM
matriculation. st in FM had a rapid first-decade rise to 14%, a second 1990's
surge, followed by a drop to the current plateau of 8-9%. This falls far short of
the 30-50% generalist benchmark needed to fill the country's healthcare needs.
Curricular innovations fall into three periods: Charismatic Leaders & Clinical
Exposures (1965-1978), Creation of Clerkships of FM (1979-1998) and Curricular
Innovations (1998 - present). There is good evidence that having a required third
year clerkship positively impacts student interest in the field, however there is
little research regarding the recruitment impact of specific clerkship curricula.
Other tools associated with student interest include programming geared towards
primary care or rural training and extracurricular opportunities such as FM
Interest Groups. Strategic plans to improve the primary care work force should
focus funding and legislative efforts on effective methods such as: establishing
and maintaining FM clerkships, admitting students with rural and underserved
backgrounds or primary care interest, developing longitudinal primary care
tracks, and supporting extracurricular FM activities. Rigorous research is needed
to assess how best to utilize limited educational resources to ensure that all
students graduate with a core set of FM competence as well as an increased FM
matriculation.
PMID- 28414408
TI - Family Medicine Research in the United States From the late 1960s Into the
Future.
AB - BACKGROUND: When the new field of family medicine research began a half century
ago, multiple individuals and organizations emphasized that research was a key
mission. Since the field's inception, there have been notable research successes
for which family medicine organizations, researchers, and leaders-assisted by
federal and state governments and private foundations-can take credit. Research
is a requirement for family medicine residency programs but not individual
residents, and multiple family medicine departments offer research training in
various forms for learners at all levels, including research fellowships. Family
physicians have developed practice-based research networks (PBRNs) to conduct
investigations and generate new knowledge. The field of family medicine has seen
the creation of new journals to support the publication of research relevant to
practicing family physicians. Nonetheless, in spite of much growth and many
successes, family physicians and their research have been underrepresented in
research funding. Clinical presentations in family medicine are often complex,
poorly-differentiated, and exist as one of several patient complaints and
diagnoses, and are not well-covered by the narrow basic-science and specialty
research that defines most of the biomedical research enterprise. Overall health
in the United States would benefit from a more robust research participation and
greater support for family medicine research.
PMID- 28414409
TI - Fifty Years of Contributions of Behavioral Science in Family Medicine.
PMID- 28414410
TI - Preparing Family Physicians to Care for Underserved Populations: A Historical
Perspective.
AB - BACKGROUND: Family physicians have been involved in the care of rural and urban
underserved populations since the founding of the specialty. In the early 1970s
family medicine training programs specifically focused on training residents to
work with the underserved were established in both urban and rural settings. Key
to the success of these programs has been a specific focus on improving access to
care, understanding and eliminating health disparities, cultural competency and
behavioral science training that recognizes the challenges often faced by
patients and families living in poor rural and urban areas of the country. In
keeping with a focus on the underserved, several urban underserved residencies
also became national models for the provision of primary care to patients and
families affected by HIV/AIDS. Family medicine training programs focused on the
underserved have resulted in the development of a cohort of family physicians who
care for those most in need in the United States. Despite these achievements,
persistent challenges remain in providing adequate access to care for many living
in rural and inner city settings. New strategies will need to be developed by
family medicine programs and others to better meet these challenges.
PMID- 28414411
TI - Contribution of Osteopathic Training to the Primary Care Workforce.
PMID- 28414412
TI - Response to "Contribution of Osteopathic Training to the Primary Care Workforce".
PMID- 28414413
TI - Medical Student Career Choice: Comparing the Social Accountability of Canadian
and American Medical Schools.
PMID- 28414414
TI - Response to "Medical Student Career Choice: Comparing the Social Accountability
of Canadian and American Medical Schools".
PMID- 28414415
TI - Ultrasonography for confirmation of gastric tube placement.
AB - BACKGROUND: Gastric tubes are commonly used for the administration of drugs and
tube feeding for people who are unable to swallow. Feeding via a tube misplaced
in the trachea can result in severe pneumonia. Therefore, the confirmation of
tube placement in the stomach after tube insertion is important. Recent studies
have reported that ultrasonography provides good diagnostic accuracy estimates in
the confirmation of appropriate tube placement. Hence, ultrasound could provide a
promising alternative to X-rays in the confirmation of tube placement, especially
in settings where X-ray facilities are unavailable or difficult to access.
OBJECTIVES: To assess the diagnostic accuracy of ultrasound for gastric tube
placement confirmation. SEARCH METHODS: We searched the Cochrane Library (2016,
Issue 3), MEDLINE (to March 2016), Embase (to March 2016), National Institute for
Health Research (NIHR) PROSPERO Register (to May 2016), Aggressive Research
Intelligence Facility Databases (to May 2016), ClinicalTrials.gov (to May 2016),
ISRCTN registry (May 2016), World Health Organization International Clinical
Trials Registry Platform (to May 2016) and reference lists of articles, and
contacted study authors. SELECTION CRITERIA: We included studies that evaluated
the diagnostic accuracy of naso- and orogastric tube placement confirmed by
ultrasound visualization using X-ray visualization as the reference standard. We
included cross-sectional studies, and case-control studies. We excluded case
series or case reports. Studies were excluded if X-ray visualization was not the
reference standard or if the tube being placed was a gastrostomy or enteric tube.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk
of bias and extracted data from each of the included studies. We contacted
authors of the included studies to obtain missing data. MAIN RESULTS: We
identified 10 studies (545 participants and 560 tube insertions) which met our
inclusion criteria.No study was assigned low risk of bias or low concern in every
QUADAS-2 domain. We judged only three (30%) studies to have low risk of bias in
the participant selection domain because they performed ultrasound after they
confirmed correct position by other methods.Few data (43 participants) were
available for misplacement detection (specificity) due to the low incidence of
misplacement. We did not perform a meta-analysis because of considerable
heterogeneity of the index test such as the difference of echo window, the
combination of ultrasound with other confirmation methods (e.g. saline flush
visualization by ultrasound) and ultrasound during the insertion of the tube. For
all settings, sensitivity estimates for individual studies ranged from 0.50 to
1.00 and specificity estimates from 0.17 to 1.00. For settings where X-ray was
not readily available and participants underwent gastric tube insertion for
drainage (four studies, 305 participants), sensitivity estimates of ultrasound in
combination with other confirmatory tests ranged from 0.86 to 0.98 and
specificity estimates of 1.00 with wide confidence intervals.For the studies
using ultrasound alone (four studies, 314 participants), sensitivity estimates
ranged from 0.91 to 0.98 and specificity estimates from 0.67 to 1.00. AUTHORS'
CONCLUSIONS: Of 10 studies that assessed the diagnostic accuracy of gastric tube
placement, few studies had a low risk of bias. Based on limited evidence,
ultrasound does not have sufficient accuracy as a single test to confirm gastric
tube placement. However, in settings where X-ray is not readily available,
ultrasound may be useful to detect misplaced gastric tubes. Larger studies are
needed to determine the possibility of adverse events when ultrasound is used to
confirm tube placement.
PMID- 28414416
TI - BUDGET IMPACT ANALYSIS OF USING OMEPRAZOLE IMMEDIATE-RELEASE ORAL SUSPENSION IN
REPLACE OF INTRAVENOUS PANTOPRAZOLE IN CRITICALLY ILL PATIENTS.
AB - OBJECTIVES: The aim of the present study was to estimate the financial
consequence of using omeprazole immediate-release (IR) oral suspension versus
pantoprazole intravenous infusion for preventing stress-related upper
gastrointestinal bleeding in critically ill patients from the perspective of the
health care system. METHODS: An Excel-based model was developed to compare the
cost of prevention of upper gastrointestinal bleeding early after intensive care
admission using the current intravenous (IV) pantoprazole formulation versus
omeprazole IR oral suspension. Total costs included the cost of acid suppressive
drugs and related clinical outcomes. Inputs were obtained from a local clinical
trial, the Ministry of Health database, insurance organizations, hospital and
pharmacy registries, the relevant literature, and expert opinion. The robustness
of the input data was investigated by one-way sensitivity analysis. The model was
developed based on the results of a randomized control trial (RCT), in which
experimental and control groups received omeprazole and pantoprazole,
respectively. RESULTS: According to the proposed model, the cost of
gastrointestinal (GI) bleeding prevention using pantoprazole IV was US$ 950,000
while US$ 750,000 was spent on receiving omeprazole oral suspension. These costs
led to the annual cost-saving of almost US$ 200,000 (US$4 per member, per month)
for the health care system. CONCLUSIONS: In the present study, a budget impact
analysis was performed to assess the financial consequences of using omeprazole
IR oral suspension in place of pantoprazole IV for prevention of upper
gastrointestinal bleeding. The better preventive effect of omeprazole IR oral
suspension when compared with conventional therapy using pantoprazole IV was the
major reason for the final comparative budgetary savings.
PMID- 28414417
TI - Graphene Nanoprobes for Real-Time Monitoring of Isothermal Nucleic Acid
Amplification.
AB - Isothermal amplification is an efficient way to amplify DNA with high accuracy;
however, the real-time monitoring for quantification analysis mostly relied on
expensive and precisely designed probes. In the present study, a graphene oxide
(GO)-based nanoprobe was used to real-time monitor the isothermal amplification
process. The interaction between GO and different DNA structures was
systematically investigated, including single-stranded DNA (ssDNA), double
stranded DNA (dsDNA), DNA 3-helix, and long rolling circle amplification (RCA)
and hybridization chain reaction (HCR) products, which existed in one-, two-, and
three-dimensional structures. It was found that the high rigid structures
exhibited much lower affinity with GO than soft ssDNA, and generally the rigidity
was dependent on the length of targets and the hybridization position with probe
DNA. On the basis of these results, we successfully monitored HCR amplification
process, RCA process, and the enzyme restriction of RCA products with GO
nanoprobe; other applications including the detection of the assembly/disassembly
of DNA 3-helix structures were also performed. Compared to the widely used end
point detection methods, the GO-based sensing platform is simple, sensitive, cost
effective, and especially in a real-time monitoring mode. We believe such studies
can provide comprehensive understandings and evocation on design of GO-based
biosensors for broad application in various fields.
PMID- 28414418
TI - Novel Composite Proton Exchange Membrane with Connected Long-Range Ionic
Nanochannels Constructed via Exfoliated Nafion-Boron Nitride Nanocomposite.
AB - Nafion-boron nitride (NBN) nanocomposites with a Nafion-functionalized periphery
are prepared via a convenient and ecofriendly Nafion-assisted water-phase
exfoliation method. Nafion and the boron nitride nanosheet present strong
interactions in the NBN nanocomposite. Then the NBN nanocomposites were blended
with Nafion to prepare NBN Nafion composite proton exchange membranes (PEMs). NBN
nanocomposites show good dispersibility and have a noticeable impact on the
aggregation structure of the Nafion matrix. Connected long-range ionic
nanochannels containing exaggerated (-SO3-)n ionic clusters are constructed
during the membrane-forming process via the hydrophilic and H-bonding
interactions between NBN nanocomposites and Nafion matrix. The addition of NBN
nanocomposites with sulfonic groups also provides additional proton
transportation spots and enhances the water uptake of the composite PEMs. The
proton conductivity of the NBN Nafion composite PEMs is significantly increased
under various conditions relative to that of recast Nafion. At 80 degrees C-95%
relative humidity, the proton conductivity of 0.5 NBN Nafion is 0.33 S.cm-1, 6
times that of recast Nafion under the same conditions.
PMID- 28414419
TI - Photoswitchable Inhibitor of a Glutamate Transporter.
AB - Excitatory amino acid transporters clear glutamate from the synaptic cleft and
play a critical role in glutamatergic neurotransmission. Their differential roles
in astrocytes, microglia, and neurons are poorly understood due in part to a lack
of pharmacological tools that can be targeted to specific cells and tissues. We
now describe a photoswitchable inhibitor, termed ATT, that interacts with the
major mammalian forebrain transporters EAAT1-3 in a manner that can be reversibly
switched between trans (high-affinity) and cis (low-affinity) configurations
using light of different colors. In the dark, ATT competitively inhibited the
predominant glial transporter EAAT2 with ~200-fold selectivity over the neuronal
transporter EAAT3. Brief exposure to 350 nm light reduced the steady-state
blocker affinity by more than an order of magnitude. Illumination of EAAT2
complexed with ATT induced a corresponding increase in the blocker off-rate
monitored in the presence of glutamate. ATT can be used to reversibly manipulate
glutamate transporter activity with light and may be useful to gain insights into
the dynamic physiological roles of glutamate transporters in the brain, as well
as to study the molecular interactions of transporters with ligands.
PMID- 28414420
TI - Systematic Synthesis and Binding Study of HIV V3 Glycopeptides Reveal the Fine
Epitopes of Several Broadly Neutralizing Antibodies.
AB - A class of new glycan-reactive broadly neutralizing antibodies represented by
PGT121, 10-1074, and PGT128 has recently been discovered that targets specific N
glycans and the peptide region around the V3 domain. However, the glycan
specificity and fine epitopes of these bNAbs remain to be further defined. We
report here a systematic chemoenzymatic synthesis of homogeneous V3 glycopeptides
derived from the HIV-1 JR-FL strain carrying defined N-glycans at N332, N301, and
N295 sites. Antibody binding studies revealed that both the nature and site of
glycosylation in the context of the V3 domain were critical for high-affinity
binding. It was found that antibody PGT128 exhibited specificity for high-mannose
N-glycan with glycosylation site promiscuity, PGT121 showed binding specificity
for glycopeptide carrying a sialylated N-glycan at N301 site, and 10-1074 was
specific for glycopeptide carrying a high-mannose N-glycan at N332 site. The
synthesis and binding studies permit a detailed assessment of the glycan
specificity and the requirement of peptide in the context of antibody-antigen
recognition. The identified glycopeptides can be used as potential templates for
HIV vaccine design.
PMID- 28414421
TI - Shape-Controlled Metal-Free Catalysts: Facet-Sensitive Catalytic Activity Induced
by the Arrangement Pattern of Noncovalent Supramolecular Chains.
AB - Metal-free catalytic materials have recently received broad attention as
promising alternatives to metal-involved catalysts. This is owing to their
inherent capability to overcome the inevitable limitations of metal-involved
catalysts, such as high sensitivity to poisoning, the limited reserves, high cost
and scarcity of metals (especially noble metals), etc. However, the lack of shape
controlled metal-free catalysts with well-defined facets is a formidable
bottleneck limiting our understandings on the underlying structure-activity
relationship at atomic/molecular level, which thereby restrains their rational
design. Here, we report that catalytically active crystals of a porphyrin,
5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, could be shaped into well
defined cubes and sheet-like tetradecahedrons (TDHD), which are exclusively and
predominantly enclosed by {101} and {001} facets, respectively. Fascinatingly,
compared to the cubes, the TDHDs display substantially enhanced catalytic
activity toward water decontamination under visible-light irradiation, although
both the architectures have identical crystalline structure. We disclose that
such interesting shape-sensitive catalytic activity is ascribed to the distinct
spatial separation efficiency of photogenerated electrons and holes induced by
single-channel and multichannel charge transport pathways along noncovalent
supramolecular chains, which are arranged as parallel-aligned and 2D network
patterns, respectively. Our findings provide an ideal scientific platform to
guide the rational design of next-generation metal-free catalysts of desired
catalytic performances.
PMID- 28414422
TI - Synthesis and Structure-Activity Relationships of Tool Compounds Based on
WAY163909, a 5-HT2C Receptor Agonist.
AB - The development of probe molecules that can be used to investigate G protein
coupled receptor (GPCR) pharmacology, trafficking, and relationship with other
GPCRs is an important and growing area of research. Here, we report the synthesis
of analogues of the known selective serotonin (5-HT) 5-HT2C receptor (5-HT2CR)
agonist WAY163909 which were designed to allow for the attachment of a second
ligand, signaling or reporter molecules, as well as immobilization agents to the
parent molecule with the maintenance of agonist activity. This goal was
accomplished by the synthesis of novel molecules in which sites a-d were modified
and resulting compounds were analyzed pharmacologically in vitro.
PMID- 28414423
TI - Robust Fluorine-Free Superhydrophobic Amino-Silicone Oil/SiO2 Modification of
Electrospun Polyacrylonitrile Membranes for Waterproof-Breathable Application.
AB - Superhydrophobic waterproof-breathable membranes have attracted considerable
interest owing to their multifunctional applications in self-cleaning, anti
icing, anticorrosion, outdoor tents, and protective clothing. Despite the
researches pertaning to the construction of superhydrophobic functional membranes
by nanoparticle finishing have increased drastically, the disconnected particle
component is easy to fall off from the membranes under deformation and wear
conditions, which has restricted their wide use in practice. Here, robust
superhydrophobic microporous membranes were prepared via a facile and
environmentally friendly strategy by dip-coating amino-silicone oil (ASO) onto
the electrospun polyacrylonitrile (PAN) membranes, followed by SiO2 nanoparticles
(SiO2 NPs) blade coating. Compared with hydrophilic PAN membranes, the modified
membranes exhibited superhydrophobic surface with an advancing water contact
angle up to 156 degrees , after introducing ASO as low surface energy substance
and SiO2 NPs as filler to reduce the pore size and construct the
multihierarchical rough structure. Varying the concentrations of ASO and SiO2 NPs
systematically, the PAN electrospun membranes modified with 1 wt % ASO and 0.1 wt
% SiO2 NPs were endowed with good water-resistance (74.3 kPa), relative low
thermal conductivity (0.0028 W m-1 K-1), modest vapor permeability (11.4 kg m-2 d
1), and air permeability (20.5 mm s-1). Besides, the inorganic-organic hybrid
coating of ASO/SiO2 NPs could maintain its superhydrophobicity even after 40
abrasion cycles. The resulting membranes were found to resist variations on the
pH scale from 0 to 12, and retained their water repellent properties when exposed
to harsh acidic and alkali conditions. This facile fabrication of durable
fluorine-free superhydrophobic membranes simultaneous with good waterproof
breathable performance provides the advantages for potential applications in self
cleaning materials and versatile protective clothing.
PMID- 28414424
TI - Quantifying the Hierarchical Order in Self-Aligned Carbon Nanotubes from Atomic
to Micrometer Scale.
AB - Fundamental understanding of structure-property relationships in hierarchically
organized nanostructures is crucial for the development of new functionality, yet
quantifying structure across multiple length scales is challenging. In this work,
we used nondestructive X-ray scattering to quantitatively map the multiscale
structure of hierarchically self-organized carbon nanotube (CNT) "forests" across
4 orders of magnitude in length scale, from 2.0 A to 1.5 MUm. Fully resolved
structural features include the graphitic honeycomb lattice and interlayer walls
(atomic), CNT diameter (nano), as well as the greater CNT ensemble (meso) and
large corrugations (micro). Correlating orientational order across hierarchical
levels revealed a cascading decrease as we probed finer structural feature sizes
with enhanced sensitivity to small-scale disorder. Furthermore, we established
qualitative relationships for single-, few-, and multiwall CNT forest
characteristics, showing that multiscale orientational order is directly
correlated with number density spanning 109-1012 cm-2, yet order is inversely
proportional to CNT diameter, number of walls, and atomic defects. Lastly, we
captured and quantified ultralow-q meridional scattering features and built a
phenomenological model of the large-scale CNT forest morphology, which predicted
and confirmed that these features arise due to microscale corrugations along the
vertical forest direction. Providing detailed structural information at multiple
length scales is important for design and synthesis of CNT materials as well as
other hierarchically organized nanostructures.
PMID- 28414425
TI - Tunable UV- and Visible-Light Photoresponse Based on p-ZnO Nanostructures/n
ZnO/Glass Peppered with Au Nanoparticles.
AB - UV- and visible-light photoresponse was achieved via p-type K-doped ZnO nanowires
and nanosheets that were hydrothermally synthesized on an n-ZnO/glass substrate
and peppered with Au nanoparticles. The K content of the p-ZnO nanostructures was
0.36 atom %. The UV- and visible-light photoresponse of the p-ZnO
nanostructures/n-ZnO sample was roughly 2 times higher than that of the ZnO
nanowires. The Au nanoparticles of various densities and diameter sizes were
deposited on the p-ZnO nanostructures/n-ZnO samples by a simple UV photochemical
reaction method yielding a tunable and enhanced UV- and visible-light
photoresponse. The maximum UV and visible photoresponse of the Au nanoparticle
sample was obtained when the diameter size of the Au nanoparticle was
approximately 5-35 nm. On the basis of the localized surface plasmon resonance
effect, the UV, blue, and green photocurrent/dark current ratios of Au
nanoparticle/p-ZnO nanostructures/n-ZnO are ~1165, ~94.6, and ~9.7, respectively.
PMID- 28414426
TI - Two Distinct Assembly States of the Cysteine Regulatory Complex of Salmonella
typhimurium Are Regulated by Enzyme-Substrate Cognate Pairs.
AB - Serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS), which
catalyze the last two steps of cysteine biosynthesis, interact and form the
cysteine regulatory complex (CRC). The current model of Salmonella typhimurium
predicts that CRC is composed of one [SAT]hexamer unit and two molecules of
[OASS]dimer. However, it is not clear why [SAT]hexamer cannot engage all of its
six high-affinity binding sites. We examined the assembly state(s) of CRC by size
exclusion chromatography, analytical ultracentrifugation (AUC), isothermal
titration calorimetry (ITC), and surface plasmon resonance (SPR) approaches. We
show that CRC exists in two major assembly states, low-molecular weight (CRC1;
1[SAT]hexamer + 2[OASS]dimer) and high-molecular weight (CRC2; 1[SAT]hexamer +
4[OASS]dimer) states. Along with AUC results, ITC and SPR studies show that
[OASS]dimer binds to [SAT]hexamer in a stepwise manner but the formation of fully
saturated CRC3 (1[SAT]hexamer + 6[OASS]dimer) is not favorable. The fraction of
CRC2 increases as the [OASS]dimer/[SAT]hexamer ratio increases to >4-fold, but
CRC2 can be selectively dissociated into either CRC1 or free enzymes, in the
presence of OAS and sulfide, in a concentration-dependent manner. Together, we
show that CRC is a regulatable multienzyme assembly, sensitive to OASS
substrate(s) levels but subject to negative cooperativity and steric hindrance.
Our results constitute the first report of the dual-assembly-state nature of CRC
and suggest that physiological conditions, which limit sulfate uptake, would
favor CRC1 over CRC2.
PMID- 28414428
TI - Low-Temperature Trapping of Intermediates in the Reaction of NO* with O2.
AB - The autoxidation of NO* was studied in glass-like matrices of 2-methylbutane at
110 K and in a 8:3 v/v mixture of 2,2-dimethylbutane and n-pentane (rigisolve) at
80-90 K, by letting gaseous NO* diffuse into these solvents that were saturated
with O2. In 2-methyllbutane, we observed a red compound. However, in rigisolve at
85-90 K, a bright yellow color appears that turns red when the sample is warmed
by 10-20 K. The new yellow compound is a precursor of the red one and also
diamagnetic. The UV-vis spectrum of the yellow compound contains a band which
resembles that present in ONOO-. Because the red and yellow intermediates are not
paramagnetic, we postulate that O?N-O-O* is in close contact with NO*, or with
another O?N-O-O*. Diffusion of gaseous O2 into rigisolve saturated with NO* does
not produce a color; however, a weak EPR signal (g = 2.010) is observed. This
signal most likely indicates the presence of ONOO*. These findings complement our
earlier observation of a red color at low temperatures and the presence of ONOO*
in the gas phase (Galliker, B.; Kissner, R.; Nauser, T.; Koppenol, W. H. Chem.
Eur. J. 2009, 15, 6161-6168), and they indicate that the termolecular
autoxidation of nitrogen monoxide proceeds via the intermediate ONOO* and not via
N2O2.
PMID- 28414427
TI - Enhancing Extracellular Electron Transfer of Shewanella oneidensis MR-1 through
Coupling Improved Flavin Synthesis and Metal-Reducing Conduit for Pollutant
Degradation.
AB - Dissimilatory metal reducing bacteria (DMRB) are capable of extracellular
electron transfer (EET) to insoluble metal oxides, which are used as external
electron acceptors by DMRB for their anaerobic respiration. The EET process has
important contribution to environmental remediation mineral cycling, and
bioelectrochemical systems. However, the low EET efficiency remains to be one of
the major bottlenecks for its practical applications for pollutant degradation.
In this work, Shewanella oneidensis MR-1, a model DMRB, was used to examine the
feasibility of enhancing the EET and its biodegradation capacity through genetic
engineering. A flavin biosynthesis gene cluster ribD-ribC-ribBA-ribE and metal
reducing conduit biosynthesis gene cluster mtrC-mtrA-mtrB were coexpressed in S.
oneidensis MR-1. Compared to the control strain, the engineered strain was found
to exhibit an improved EET capacity in microbial fuel cells and potentiostat
controlled electrochemical cells, with an increase in maximum current density by
approximate 110% and 87%, respectively. The electrochemical impedance
spectroscopy (EIS) analysis showed that the current increase correlated with the
lower interfacial charge-transfer resistance of the engineered strain. Meanwhile,
a three times more rapid removal rate of methyl orange by the engineered strain
confirmed the improvement of its EET and biodegradation ability. Our results
demonstrate that coupling of improved synthesis of mediators and metal-reducing
conduits could be an efficient strategy to enhance EET in S. oneidensis MR-1,
which is essential to the applications of DMRB for environmental remediation,
wastewater treatment, and bioenergy recovery from wastes.
PMID- 28414429
TI - Sublethal Lead Exposure Alters Movement Behavior in Free-Ranging Golden Eagles.
AB - Lead poisoning of animals due to ingestion of fragments from lead-based
ammunition in carcasses and offal of shot wildlife is acknowledged globally and
raises great concerns about potential behavioral effects leading to increased
mortality risks. Lead levels in blood were correlated with progress of the moose
hunting season. Based on analyses of tracking data, we found that even sublethal
lead concentrations in blood (25 ppb, wet weight), can likely negatively affect
movement behavior (flight height and movement rate) of free-ranging scavenging
Golden Eagles (Aquila chrysaetos). Lead levels in liver of recovered post-mortem
analyzed eagles suggested that sublethal exposure increases the risk of mortality
in eagles. Such adverse effects on animals are probably common worldwide and
across species, where game hunting with lead-based ammunition is widespread. Our
study highlights lead exposure as a considerably more serious threat to wildlife
conservation than previously realized and suggests implementation of bans of lead
ammunition for hunting.
PMID- 28414430
TI - Palladium Catalyzed Asymmetric Three-Component Coupling of Boronic Esters,
Indoles, and Allylic Acetates.
AB - Boronic esters react with 2-lithiated indoles to form boronate intermediates. The
boronate reacts with allylic acetates in the presence of (BINAP)Pd catalysts to
allylate C3 concurrent with alkyl migration from B to C2 of the indole. Overall,
the process is a three-component coupling that joins an allylic acetate, and
indole and an organo-B(pin) species to provide substituted indoles and indolines
with high enantio-, regio-, and diastereoselectivity.
PMID- 28414431
TI - Mononuclear Sulfido-Tungsten(V) Complexes: Completing the Tp*MEXY (M = Mo, W; E =
O, S) Series.
AB - Orange Tp*WSCl2 has been synthesized from the reactions of Tp*WOCl2 with boron
sulfide in refluxing toluene or Tp*WS2Cl with PPh3 in dichloromethane at room
temperature. Mononuclear sulfido-tungsten(V) complexes, Tp*WSXY {X = Y = Cl, OPh,
SPh, SePh; X = Cl, Y = OPh; XY = toluene-3,4-dithiolate (tdt), quinoxaline-2,3
dithiolate (qdt); and Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate} were
prepared by metathesis of Tp*WSCl2 with the respective alkali metal salt of X
/XY2-, or [NHEt3]2(qdt). The complexes were characterized by microanalysis, mass
spectrometry, electrochemistry, and infrared (IR), electron paramagnetic
resonance (EPR) and electronic absorption spectroscopies. The molecular
structures of Tp*WS(OPh)2, Tp*WS(SePh)2, and Tp*WS(tdt) have been determined by X
ray crystallography. The six-coordinate, distorted-octahedral W centers are
coordinated by terminal sulfido (W=S = 2.128(2) - 2.161(1) A), terdentate facial
Tp*, and monodentate/bidentate O/S/Se-donor ligands. The sulfido-W(V) complexes
are characterized by lower energy electronic transitions, smaller giso, and
larger Aiso(183W) values, and more positive reduction potentials compared with
their oxo-W(V) counterparts. This series has been probed by sulfur K-edge X-ray
absorption spectroscopy (XAS), the spectra being assigned by comparison to
Tp*WOXY (X = Y = SPh; XY = tdt, qdt) and time-dependent density functional
theoretical (TD-DFT) calculations. This study provides insight into the
electronic nature and chemistry of the catalytically and biologically important
sulfido-W unit.
PMID- 28414432
TI - Synthetic Transformations Using Molecular Oxygen-Doped Carbon Materials.
AB - Carbon materials like activated carbon (AC) undergo chemisorption with O2 to give
species with electron deficiency in the carbon skeleton and negative charge at
the oxygen end that upon reaction with PPh3 and benzoic acid afford Ph3P?O.
Whereas amine donors react with O2-chemisorbed AC and nucleophiles to give
dehydrogenatively coupled products in 67-89% yields via the corresponding radical
cation and iminium ion intermediates, the reactions using beta-naphthoxide
derivatives give the corresponding oxidatively coupled bi-2-naphthol products in
68-95% yields.
PMID- 28414433
TI - Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed
Carboamination/Cyclopropanation Reactions between N-Enoxyphthalimides and
Alkenes.
AB - Recently, a new synthetic methodology of rhodium-catalyzed
carboamination/cyclopropanation from the same starting materials at different
reaction conditions has been reported. It provides an efficient strategy for the
stereospecific formation of both carbon- and nitrogen-based functionalities
across an alkene. Herein we carried out a detailed theoretical mechanistic
exploration for the reactions to elucidate the switch between carboamination and
cyclopropanation as well as the origin of the chemoselectivity. Instead of the
experimentally proposed RhIII-RhI-RhIII catalytic mechanism, our results reveal
that the RhIII-RhV-RhIII mechanism is much more favorable in the two reactions.
The chemoselectivity is attributed to a combination of electronic and steric
effects in the reductive elimination step. The interactions between alkene and
the rhodacycle during the alkene migration insertion control the
stereoselectivity in the carboamination reactions. The present results disclose a
dual role of the methanol solvent in controlling the chemoselectivity.
PMID- 28414434
TI - Ammonia Activation, H2 Evolution and Nitride Formation from a Molybdenum Complex
with a Chemically and Redox Noninnocent Ligand.
AB - Treatment of the bis(imino)pyridine molybdenum eta6-benzene complex
(iPrPDI)Mo(eta6-C6H6) (iPrPDI, 2,6-(2,6-iPr2C6H3N?CMe)2C5H3N) with NH3 resulted
in coordination induced haptotropic rearrangement of the arene to form
(iPrPDI)Mo(NH3)2(eta2-C6H6). Analogous eta2-ethylene and eta2-cyclohexene
complexes were also synthesized, and the latter was crystallographically
characterized. All three compounds undergo loss of the eta2-coordinated ligand
followed by N-H bond activation, bis(imino)pyridine modification, and H2 loss. A
dual ammonia activation approach has been discovered whereby reversible M-L
cooperativity and coordination induced bond weakening likely contribute to
dihydrogen formation. Significantly, the weakened N-H bonds in
(iPrPDI)Mo(NH3)2(eta2-C2H4) enabled hydrogen atom abstraction and synthesis of a
terminal nitride from coordinated ammonia, a key step in NH3 oxidation.
PMID- 28414436
TI - Pressure-Temperature Phase Diagram Reveals Spin-Lattice Interactions in
Co[N(CN)2]2.
AB - Diamond anvil cell techniques, synchrotron-based infrared and Raman
spectroscopies, and lattice dynamics calculations are combined with prior
magnetic property work to reveal the pressure-temperature phase diagram of
Co[N(CN)2]2. The second-order structural boundaries converge on key areas of
activity involving the spin state exposing how the pressure-induced local lattice
distortions trigger the ferromagnetic -> antiferromagnetic transition in this
quantum material.
PMID- 28414435
TI - Synthesis of BODIPY-Peptide Conjugates for Fluorescence Labeling of EGFR
Overexpressing Cells.
AB - Regioselective functionalization of 2,3,5,6,8-pentachloro-BODIPY 1 produced
unsymmetric BODIPY 5, bearing an isothiocyanate group suitable for conjugation,
in only four steps. The X-ray structure of 5 reveals a nearly planar BODIPY core
with aryl dihedral angles in the range 47.4-62.9 degrees . Conjugation of 5 to
two EGFR-targeting pegylated peptides, 3PEG-LARLLT (6) and 3PEG-GYHWYGYTPQNVI
(7), under mild conditions (30 min at room temperature), afforded BODIPY
conjugates 8 and 9 in 50-80% isolated yields. These conjugates showed red-shifted
absorption and emission spectra compared with 5, in the near-IR region, and were
evaluated as potential fluorescence imaging agents for EGFR overexpressing cells.
SPR and docking investigations suggested that conjugate 8 bearing the LARLLT
sequence binds to EGFR more effectively than 9 bearing the GYHWYGYTPQNVI peptide,
in part due to the lower solubility of 9, and its tendency for aggregation at
concentrations above 10 MUM. Studies in human carcinoma HEp2 cells overexpressing
EGFR demonstrated low dark and photo cytotoxicities for BODIPY 5 and the two
peptide conjugates, and remarkably high cellular uptake for both conjugates 8 and
9, up to 90-fold compared with BODIPY 5 after 1 h. Fluorescence imaging studies
in HEp2 cells revealed subcellular localization of the BODIPY-peptide conjugates
mainly in the Golgi apparatus and the cell lysosomes. The low cytotoxicity of the
new conjugates and their remarkably high uptake into EGFR overexpressing cells
renders them promising imaging agents for cancers overexpressing EGFR.
PMID- 28414437
TI - Phenolic Content and Antioxidant Activity during the Development of 'Brookfield'
and 'Mishima' Apples.
AB - The aim of this study was to characterize the changes in the contents of total
(TPC) and individual (IPC) phenolic compounds, the total antioxidant activity
(TAA) in the peel and pulp, and total anthocyanins (TAN) in the peel during the
development of the fruits of 'Brookfield' and 'Mishima' apple trees. 'Brookfield'
apples were harvested from the 49th to the 138th days after full bloom (DAFB) and
'Mishima' apples from the 45th to the 172th DAFB. In the pulp, the IPC, TPC, and
TAA rapidly reduced at 75 and 79 DAFB for the 'Brookfield' and 'Mishima' apples,
respectively, and then remained constant until commercial maturity. In the peel
of 'Brookfield' apples there was a reduction in the TPC and TAA at 79 DAFB. The
quercetin 3-galactoside, epicatechin, and procyanidin B2 contents reduced up to
107 DAFB with a subsequent increase in the values at commercial maturity. In the
peel of 'Mishima' apples there was a reduction in the TPC, TAA, epicatechin, and
procyanidin B1 and B2 contents at 130 DAFB, with a subsequent increase until
commercial maturity. The TAN content in the peel increased during the 2 and 4
weeks prior to commercial maturity for 'Brookfield' and 'Mishima' apples,
respectively. In the pulp and peel of both cultivars there was a reduction in the
IPC, TPC, and TAA as the development proceeded. On nearing commercial maturity,
there was an increase in the contents of quercetin 3-galactoside, epicatechin,
procyanidin B2, and TAN in the peel for both cultivars.
PMID- 28414438
TI - Custom Coordination Environments for Lanthanoids: Tripodal Ligands Achieve Near
Perfect Octahedral Coordination for Two Dysprosium-Based Molecular Nanomagnets.
AB - Controlling the coordination sphere of lanthanoid complexes is a challenging
critical step toward controlling their relaxation properties. Here we present the
synthesis of hexacoordinated dysprosium single-molecule magnets, where tripodal
ligands achieve a near-perfect octahedral coordination. We perform a complete
experimental and theoretical investigation of their magnetic properties,
including a full single-crystal magnetic anisotropy analysis. The combination of
electrostatic and crystal-field computational tools (SIMPRE and CONDON codes)
allows us to explain the static behavior of these systems in detail.
PMID- 28414439
TI - Mitigation of Thin-Film Composite Membrane Biofouling via Immobilizing Nano-Sized
Biocidal Reservoirs in the Membrane Active Layer.
AB - This work investigates the use of a silver-based metal-organic framework (MOF)
for mitigating biofouling in forward-osmosis thin-film composite (TFC) membranes.
This is the first study of the use of MOFs for biofouling control in membranes.
MOF nanocrystals were immobilized in the active layer of the membranes via
dispersion in the organic solution used for interfacial polymerization. Field
emission scanning electron microscopy (FE-SEM) and X-ray photoelectron
spectroscopy (XPS) characterization results showed the presence of the MOF
nanocrystals in the active layer of the membranes. The immobilization improved
the membrane active layer in terms of hydrophilicity and transport properties
without adversely affecting the selectivity. It imparted antibacterial activity
to the membranes; the number of live bacteria attached to the membrane surface
was over 90% less than that of control membranes. Additionally, the MOF
nanocrystals provided biocidal activity that lasted for 6 months. The
immobilization improved biofouling resistance in the membranes, whose flux had a
decline of 8% after 24 h of operation in biofouling experiments, while that of
the control membranes had a greater decline of ~21%. The better biofouling
resistance is due to simultaneous improvement of antiadhesive and antimicrobial
properties of the membranes. Fluorescence microscopy and FE-SEM indicated
simultaneous improvement in antiadhesive and antimicrobial properties of the TFN
membranes, resulting in limited biofilm formation.
PMID- 28414440
TI - Influence of Active Layer on Separation Potentials of Nanofiltration Membranes
for Inorganic Ions.
AB - Active layers of two fully aromatic and two semi-aromatic nanofiltration
membranes were studied along with surface charge at different electrolyte
composition and effective pore size to elucidate their influence on separation
mechanisms for inorganic ions by steric, charge, and dielectric exclusion. The
membrane potential method used for pore size measurement is underlined as the
most appropriate measurement technique for this application owing to its
dependence on the diffusional potentials of inorganic ions. Crossflow rejection
experiments with dilute feed composition indicate that both fully aromatic
membranes achieved similar rejection despite the differences in surface charge,
which suggests that rejection by these membranes is exclusively dependent on size
exclusion and the contribution of charge exclusion is weak. Rejection experiments
with higher ionic strength and different composition of the feed solution
confirmed this hypothesis. On the other hand, increase in the ionic strength of
feed solution when the charge exclusion effects are negligible due to charge
screening strongly influenced ion rejection by semi-aromatic membranes. The
experimental results confirmed that charge exclusion contributes significantly to
the performance of semi-aromatic membranes in addition to size exclusion. The
contribution of dielectric exclusion to overall ion rejection would be more
significant for fully aromatic membranes.
PMID- 28414441
TI - Suppression of Enteric Bacteria by Bacteriophages: Importance of Phage
Polyvalence in the Presence of Soil Bacteria.
AB - Bacteriophages are widely recognized for their importance in microbial ecology
and bacterial control. However, little is known about how phage polyvalence
(i.e., broad host range) affects bacterial suppression and interspecies
competition in environments harboring enteric pathogens and soil bacteria. Here
we compare the efficacy of polyvalent phage PEf1 versus coliphage T4 in
suppressing a model enteric bacterium (E. coli K-12) in mixtures with soil
bacteria (Pseudomonas putida F1 and Bacillus subtilis 168). Although T4 was more
effective than PEf1 in infecting E. coli K-12 in pure cultures, PEf1 was 20-fold
more effective in suppressing E. coli under simulated multispecies biofilm
conditions because polyvalence enhanced PEf1 propagation in P. putida. In
contrast, soil bacteria do not propagate coliphages and hindered T4 diffusion
through the biofilm. Similar tests were also conducted under planktonic
conditions to discern how interspecies competition contributes to E. coli
suppression without the confounding effects of restricted phage diffusion.
Significant synergistic suppression was observed by the combined effects of
phages plus competing bacteria. T4 was slightly more effective in suppressing E.
coli in these planktonic mixed cultures, even though PEf1 reached higher
concentrations by reproducing also in P. putida (7.2 +/- 0.4 vs 6.0 +/- 1.0
log10PFU/mL). Apparently, enhanced suppression by higher PEf1 propagation was
offset by P. putida lysis, which decreased stress from interspecies competition
relative to incubations with T4. In similar planktonic tests with more competing
soil bacteria species, P. putida lysis was less critical in mitigating
interspecies competition and PEf1 eliminated E. coli faster than T4 (36 vs 42 h).
Overall, this study shows that polyvalent phages can propagate in soil bacteria
and significantly enhance suppression of co-occurring enteric species.
PMID- 28414442
TI - Stolonidiol: Synthesis, Target Identification, and Mechanism for Choline
Acetyltransferase Activation.
AB - Stolonidiol, a marine natural product, has been reported to potentiate the
activity of choline acetyltransferase (ChAT), the enzyme that produces the
neurotransmitter acetylcholine. Here we report the total synthesis of stolonidiol
starting from (R)-(+)-limonene. To identify the mechanism by which ChAT activity
is increased, we sought to identify the biological target of stolonidiol. We show
that stolonidiol binds to the phorbol ester binding site of protein kinase C
(PKC), induces translocation of PKC to the cell membrane, and activates kinase
activity. Furthermore, we confirmed the increase in ChAT activity observed upon
treatment of cells with stolonidiol and show that this effect is mediated by PKC.
Collectively, our data strongly suggest that PKC activation by stolonidiol is
responsible for the resulting potentiation of ChAT activity.
PMID- 28414443
TI - General, Mild, and Metal-Free Synthesis of Phenyl Selenoesters from Anhydrides
and Their Use in Peptide Synthesis.
AB - A mild, practical, and simple procedure for phenyl selenoesters synthesis from
several anhydrides and diphenyl diselenide was developed. This transition-metal
free method provides a straightforward entry to storable Fmoc-amino acid
selenoesters which are effective chemoselective acylating reagents. An
application to oligopeptide synthesis was illustrated.
PMID- 28414444
TI - Accurate Relative Energies and Binding Energies of Large Ice-Liquid Water
Clusters and Periodic Structures.
AB - Relative energies and binding energies are crucial quantities that determine
various molecular properties of ice and water. We developed a new effective
method to compute those energies of bulk ice-liquid water systems. In this work,
ten ice-liquid 144-mers and ten periodic ice-liquid (H2O)64 systems are taken
from the molecular dynamics simulations in the melting process of ice-Ih
crystals. They are investigated at the levels of density functional theory (DFT),
explicitly correlated second-order Moller-Plesset perturbation theory (MP2-F12),
and coupled-cluster singles and doubles with noniterative triples corrections
[CCSD(T)-F12b] in the framework of generalized energy-based fragmentation
approach. Our results show that the changing of noncovalent interactions
significantly influences the performances of DFT and electron correlation methods
for those systems in the melting process of ice. Various DFT methods predict
quite different results for ice and mixed ice-liquid structures but give similar
results for pure liquid ones. It also explains why many DFT-based simulations
lead to inaccurate densities of ice and liquid water. The CCSD(T)-F12b results
suggest that the MP2-F12 method provides satisfactory results and is expected to
be employed to simulate the phase transitions of ice crystal.
PMID- 28414445
TI - Preferential Solvation/Hydration of alpha-Chymotrypsin in Water-Acetonitrile
Mixtures.
AB - The aim of our study is to monitor the preferential hydration/solvation of the
protein macromolecules at low and high water content in water-organic mixtures.
Our approach is based on the analysis of the absolute values of the water/organic
solvent sorption. We applied this approach to estimate the protein
stabilization/destabilization due to the preferential interactions of alpha
chymotrypsin with water-acetonitrile mixtures. At high water content, alpha
chymotrypsin is preferentially hydrated. At the intermediate water content, the
preferential interaction changed from preferential hydration to preferential
binding of acetonitrile. From infrared spectra, changes in the structure of alpha
chymotrypsin were determined through an analysis of the structure of the amide I
band. Acetonitrile augments the intensity of the 1626 cm-1 band assigned to the
intermolecular beta-sheet aggregates. At low water content, the protein is in a
glassy (rigid) state. The H-bond accepting acetonitrile molecules are not
effective in solvating the dehydrated protein molecules alone. Therefore, the
acetonitrile molecules are preferentially excluded from the protein surface,
resulting in the preferential hydration. Advantages of our approach: (i) The
preferential interaction parameters can be determined in the entire range of
water content in water-organic mixtures. (ii) Our approach facilitates the
individual evaluation of the Gibbs energies of water, protein, and organic
solvent.
PMID- 28414446
TI - Radical Decarboxylation/Annulation of Acrylamides with Aliphatic Acyl Peroxides.
AB - A radical decarboxylation/annulation of acrylamides with aliphatic acyl peroxides
was developed, giving a series of linear alkylated oxindoles in moderate to good
yields. The reaction used aliphatic acyl peroxides as the linear alkyl radical
source and tolerated a broad scope of substrates under metal-free conditions,
offering a simple and efficient approach toward alkylated oxindoles.
PMID- 28414447
TI - Supramolecular Porphyrin Photosensitizers: Controllable Disguise and Photoinduced
Activation of Antibacterial Behavior.
AB - A series of supramolecular photosensitizers were fabricated from porphyrin
derivatives (Por) containing quaternary ammonium groups with cucurbit[7]uril
(CB[7]) based on host-guest interactions. The antibacterial activity of Por in
the dark could be turned off upon binding with CB[7], whereas the antibacterial
activity under white-light illumination could be turned on. In addition, its
antibacterial efficiency could be greatly enhanced by introducing metal ions.
When Pd(II) was introduced into porphyrin, its antibacterial efficiency was
enhanced from 40 to 100%. It should be noted that these small molecules showed
little to no cytotoxicity toward mammalian cells even at concentrations higher
than those under the antibacterial condition studied. This line of research will
provide a strategy for germicides consisting of quaternary ammonium groups to
fight against bacterial accumulation in the long term and holds huge potential
for application in the real world.
PMID- 28414449
TI - Time-Dependent pH Scanning of the Acid-Induced Unfolding of Human Serum Albumin
Reveals Stabilization of the Native Form by Palmitic Acid Binding.
AB - The most abundant plasma protein, human serum albumin (HSA), is known to undergo
several conformational transitions in an acidic environment. To avoid buffer
effects and correlate global and local structural changes, we developed a
continuous acidification method and simultaneously monitored the protein changes
by both small-angle scattering (SAXS) and fluorescence. The progressive
acidification, based on the hydrolysis of glucono-delta-lactone from pH 7 to pH
2.5, highlighted a multistep unfolding involving the putative F form (pH 4) and
an extended and flexible conformation (pH < 3.5). The scattering profile of the F
form was extracted by component analysis and further 3D modeled. The effect of
acid unfolding at this intermediate stage was assigned to the rearrangement of
the three albumin domains drifting apart toward a more elongated conformation,
with a partial unfolding of one of the outer domains. To test the stabilizing
effect of fatty acids, here palmitic acid, we compared the acid unfolding process
of albumin with and without ligand. We found that when binding the ligand, the
native conformation was favored up to lower pH values. Our approach solved the
problem of realizing a continuous, homogeneous, and tunable acidification with
simultaneous characterization applicable to study processes triggered by a pH
decrease.
PMID- 28414448
TI - Substrate Profiling and High Resolution Co-complex Crystal Structure of a
Secreted C11 Protease Conserved across Commensal Bacteria.
AB - Cysteine proteases are among the most abundant hydrolytic enzymes produced by
bacteria, and this diverse family of proteins have significant biological roles
in bacterial viability and environmental interactions. Members of the clostripain
like (C11) family of cysteine proteases from commensal gut bacterial strains have
recently been shown to mediate immune responses by inducing neutrophil
phagocytosis and activating bacterial pathogenic toxins. Development of
substrates, inhibitors, and probes that target C11 proteases from enteric
bacteria will help to establish the role of these proteins at the interface of
the host and microbiome in health and disease. We employed a mass spectrometry
based substrate profiling method to identify an optimal peptide substrate of
PmC11, a C11 protease secreted by the commensal bacterium Parabacteroides merdae.
Using this substrate sequence information, we synthesized a panel of fluorogenic
substrates to calculate kcat and KM and to evaluate the importance of the P2
amino acid for substrate turnover. A potent and irreversible tetrapeptide
inhibitor with a C-terminal acyloxymethyl ketone warhead, Ac-VLTK-AOMK, was then
synthesized. We determined the crystal structure of PmC11 in complex with this
inhibitor and uncovered key active-site interactions that govern PmC11 substrate
recognition and specificity. This is the first C11 protease structure in complex
with a substrate mimetic and is also the highest resolution crystal structure of
a C11 protease to date at 1.12 A resolution. Importantly, subjecting human
epithelial cell lysates to PmC11 hydrolysis in combination with subtiligase-based
N-terminal labeling and tandem mass spectrometry proteomics complemented the
stringent substrate specificity observed in the in vitro substrate profiling
experiment. The combination of chemical biological, biophysical, and biochemical
techniques presented here to elucidate and characterize PmC11 substrate
selectivity can be expanded to other proteases and the development of chemical
tools to study these essential proteins in biologically relevant samples, such as
the highly complex distal gut microbiome.
PMID- 28414450
TI - Fabrication of Au-Nanoparticle-Embedded Lipid Bilayer Membranes Supported on
Solid Substrates.
AB - We fabricated gold nanoparticle (Au-NP)-embedded supported lipid bilayers (SLBs)
by two methods. In the vesicle-vesicle fusion method, vesicles with hydrophobized
Au-NPs are ruptured and fused on SiO2/Si substrates. In the vesicle-membrane
fusion method, SLBs without Au-NPs were preformed on the substrate and then
vesicles with Au-NPs were fused into the preformed membranes. In the former
method, Au-NP incorporation into the SLBs was observed as an increase in the
membrane thickness in atomic force microscopy (AFM) images and directly observed
by transmission electron microscopy. In the latter method, fusion of vesicles
into the preformed membranes was confirmed by the fluorescent color change in the
preformed membranes, and Au-NP incorporation was also confirmed by an increase in
the membrane thickness in the AFM images. Key techniques for the successful
vesicle-membrane fusion are hydrophobization of Au-NPs, approach control of
vesicles by mixing the charged lipids, and destabilization of the lipid bilayers
by adding lipids with a small polar headgroup.
PMID- 28414451
TI - Ambient-Light-Promoted Three-Component Annulation: Synthesis of
Perfluoroalkylated Pyrimidines.
AB - An ambient-light-promoted and metal-free three-component reaction of active
methylene compounds, perfluoroalkyl iodides, and guanidines/amidines is reported.
This constitutes a powerful method to prepare perfluoroalkylated pyrimidines with
mild reaction conditions, broad substrate scope, excellent functional group
tolerance, and simple operation. A radical/polar mechanism involving the
formation of a halogen-bond adduct and radical cross-coupling is proposed.
PMID- 28414452
TI - Cation-Exchange Approach to Tuning the Flexibility of a Metal-Organic Framework
for Gated Adsorption.
AB - Achieving tailorable gated adsorption by tuning the dynamic behavior of a host
porous material is of great interest because of its practical application in gas
adsorption and separation. Here we devise a unique cation-exchange approach to
tune the dynamic behavior of a flexible anionic framework, [Zn2(bptc)(datrz)]-
(denoted as MAC-6, where H4bptc = [1,1'-biphenyl]-3,3',5,5'-tetracarboxylic acid
and Hdatrz = 3,5-diamine-1H-1,2,4-triazole), so as to realize the tailorable
gated adsorption. The CO2 adsorption amount at 273 K can be enhanced by
exchanging the counterion of protonated dimethylamine (HDMA+) with
tetraethylammonium (TEA+), tetrabutylammonium (TBA+), and tetramethylammonium
(TMA+), where the adsorption behavior is transferred from nongated to gated
adsorption. Interestingly, the Pgo for gate-opening adsorption can be further
tuned from 442 to 331 mmHg by simply adjusting the ratio of HDMA+ and TMA+. The
origin of this unique tunable property, as revealed by X-ray diffraction
experiments and structure models, is rooted at the cation-responsive
characteristic of this flexible framework.
PMID- 28414453
TI - Global Proteome Profiling of a Marine Copepod and the Mitigating Effect of Ocean
Acidification on Mercury Toxicity after Multigenerational Exposure.
AB - Previously, we found that ocean acidification (OA) mitigates mercury (Hg)
toxicity to marine copepod Tigriopus japonicus under multigenerational exposure
(four generations, F0-F3). To determine the response mechanisms of T. japonicus
against long-term exposure to OA and Hg pollution, we investigated the proteome
of F3 copepods after multigenerational exposure to four conditions: pCO2 400
MUatm + control; pCO2 1000 MUatm + control; pCO2 400 MUatm +1.0 MUg/L Hg; and
pCO2 1000 MUatm +1.0 MUg/L Hg. Functional enrichment analysis indicated that OA
enhanced the copepod's energy production mainly by increasing protein
assimilation and proteolysis as a compensatory strategy, which explained its
physiological resilience to reduced pH. Conversely, Hg treatment decreased many
critical processes, including ferric iron binding, antioxidant activity, cellular
homeostasis, and glutathione metabolism, and these toxic events could translate
into higher-level responses, i.e., restrained reproduction in copepods.
Importantly, the mediation of Hg toxicity in T. japonicus by OA could be
explained by the enhanced lysosome-autophagy pathway proteomes that are
responsible for repairing and removing damaged proteins and enzymes under stress.
Overall, this study provided molecular insights into the response of T. japonicus
to long-term exposure of OA and Hg, with a particular emphasis on the mitigating
impact of the CO2-driven acidification on Hg toxicity.
PMID- 28414454
TI - Novel Proximal Sensing for Monitoring Soil Organic C Stocks and Condition.
AB - Soil information is needed for environmental monitoring to address current
concerns over food, water and energy securities, land degradation, and climate
change. We developed the Soil Condition ANalysis System (SCANS) to help address
these needs. It integrates an automated soil core sensing system (CSS) with
statistical analytics and modeling to characterize soil at fine depth resolutions
and across landscapes. The CSS's sensors include a gamma-ray attenuation
densitometer to measure bulk density, digital cameras to image the measured soil,
and a visible-near-infrared (vis-NIR) spectrometer to measure iron oxides and
clay mineralogy. The spectra are also modeled to estimate total soil organic
carbon (C), particulate, humus, and resistant organic C (POC, HOC, and ROC,
respectively), clay content, cation exchange capacity (CEC), pH, volumetric water
content, available water capacity (AWC), and their uncertainties. Measurements of
bulk density and organic C are combined to estimate C stocks. Kalman smoothing is
used to derive complete soil property profiles with propagated uncertainties. The
SCANS provides rapid, precise, quantitative, and spatially explicit information
about the properties of soil profiles with a level of detail that is difficult to
obtain with other approaches. The information gained effectively deepens our
understanding of soil and calls attention to the central role soil plays in our
environment.
PMID- 28414455
TI - Large-Area CVD-Grown Sub-2 V ReS2 Transistors and Logic Gates.
AB - We demonstrated the fabrication of large-area ReS2 transistors and logic gates
composed of a chemical vapor deposition (CVD)-grown multilayer ReS2 semiconductor
channel and graphene electrodes. Single-layer graphene was used as the
source/drain and coplanar gate electrodes. An ion gel with an ultrahigh
capacitance effectively gated the ReS2 channel at a low voltage, below 2 V,
through a coplanar gate. The contact resistance of the ion gel-gated ReS2
transistors with graphene electrodes decreased dramatically compared with the
SiO2-devices prepared with Cr electrodes. The resulting transistors exhibited
good device performances, including a maximum electron mobility of 0.9 cm2/(V s)
and an on/off current ratio exceeding 104. NMOS logic devices, such as NOT, NAND,
and NOR gates, were assembled using the resulting transistors as a proof of
concept demonstration of the applicability of the devices to complex logic
circuits. The large-area synthesis of ReS2 semiconductors and graphene electrodes
and their applications in logic devices open up new opportunities for realizing
future flexible electronics based on 2D nanomaterials.
PMID- 28414457
TI - Electrochemically Induced Shape-Memory Behavior of Si Nanopillar-Patterned
Electrode for Li Ion Batteries.
AB - A nanopillar-patterned Si substrate was fabricated by photolithography, and its
potential as an anode material for Li ion secondary batteries was investigated.
The Si nanopillar electrode showed a capacity of ~3000 mAh g-1 during 100
charging/discharging cycles, with 98.3% capacity retention, and it was revealed
that the nanopillars underwent delithiation via a process similar to shape-memory
behavior. Despite the tensile stress and structural fractures resulting from
repeated lithiation, the nanoscale size and residual crystalline tip of the
pillar (influenced by the bulk crystalline Si base) enabled recrystallization and
transformation into a single-crystalline phase. To the best of our knowledge,
this observation of shape memory recrystallization mechanism observation was not
reported before for Si used as the active material in Li ion battery
applications; these findings are expected to provide new insights into electrode
materials for rechargeable batteries.
PMID- 28414456
TI - Interfacial Rheology of Sterically Stabilized Colloids at Liquid Interfaces and
Its Effect on the Stability of Pickering Emulsions.
AB - Particle-laden interfaces can be used to stabilize a variety of high-interface
systems, from foams over emulsions to polymer blends. The relation between the
particle interactions, the structure and rheology of the interface, and the
stability of the system remains unclear. In the present work, we experimentally
investigate how micron-sized, near-hard-sphere-like particles affect the
mechanical properties of liquid interfaces. In particular, by comparing dried and
undried samples, we investigate the effect of aggregation state on the properties
of the particle-laden liquid interface and its relation to the stability of the
corresponding Pickering emulsions. Partially aggregated suspensions give rise to
a soft-solid-like response under shear, whereas for stable PMMA particulate
layers a liquid-like behavior is observed. For interfacial creep-recovery
measurements, we present an empirical method to correct for the combined effect
of the subphase drag and the compliance of the double-wall ring geometry, which
makes a significant contribution to the apparent elasticity of weak interfaces.
We further demonstrate that both undried and dried PMMA particles can stabilize
emulsions for months, dispelling the notion that particle aggregation, in bulk or
at the interface, is required to create stable Pickering emulsions. Our results
indicate that shear rheology is a sensitive probe of colloidal interactions but
is not necessarily a predictor of the stability of interfaces, e.g., in quiescent
Pickering emulsions, as in the latter the response to dilatational deformations
can be of prime importance.
PMID- 28414458
TI - Ruthenium(II)-Catalyzed Indolo[2,1-a]isoquinolines Synthesis by Tandem C-H
Allylation and Oxidative Cyclization of 2-Phenylindoles with Allyl Carbonates.
AB - A novel RuII-catalyzed tandem C-H bond activation tool has been successfully
developed involving allylation and oxidative cyclization of 2-phenyl indoles with
allyl carbonates. This one-pot reaction is a new way to synthesize indolo[2,1
a]isoquinoline units via a simple and efficient process.
PMID- 28414459
TI - Highly Anisotropic in-Plane Excitons in Atomically Thin and Bulklike 1T'-ReSe2.
AB - Atomically thin materials such as graphene or MoS2 are of high in-plane symmetry.
Crystals with reduced symmetry hold the promise for novel optoelectronic devices
based on their anisotropy in current flow or light polarization. Here, we present
polarization-resolved optical transmission and photoluminescence spectroscopy of
excitons in 1T'-ReSe2. On reducing the crystal thickness from bulk to a
monolayer, we observe a strong blue shift of the optical band gap from 1.37 to
1.50 eV. The excitons are strongly polarized with dipole vectors along different
crystal directions, which persist from bulk down to monolayer thickness. The
experimental results are well reproduced by ab initio calculations based on the
GW-BSE approach within LDA+GdW approximation. The excitons have high binding
energies of 860 meV for the monolayer and 120 meV for bulk. They are strongly
confined within a single layer even for the bulk crystal. In addition, we find in
our calculations a direct band gap in 1T'-ReSe2 regardless of crystal thickness,
indicating weak interlayer coupling effects on the band gap characteristics. Our
results pave the way for polarization-sensitive applications, such as optical
logic circuits operating in the infrared spectral region.
PMID- 28414460
TI - Analysis of Novel Interactions between Components of the Selenocysteine
Biosynthesis Pathway, SEPHS1, SEPHS2, SEPSECS, and SECp43.
AB - In mammalian cells, the incorporation of the 21st amino acid, selenocysteine,
into proteins is guided by the Sec machinery. The function of this protein
complex requires several protein-protein and protein-RNA interactions, leading to
the incorporation of selenocysteine at UGA codons. It is guided by stem-loop
structures localized in the 3' untranslated regions of the selenoprotein-encoding
genes. Here, we conducted a global analysis of interactions between the Sec
biosynthesis and incorporation components using a bioluminescence resonance
energy transfer assay in mammalian cells that showed that selenocysteine synthase
(SEPSECS), SECp43, and selenophosphate synthetases SEPHS1 and SEPHS2 form
oligomers in eukaryotic cells. We also showed that SEPHS2 interacts with SEPSECS
and SEPHS1; these interactions were confirmed by co-immunoprecipitation. To
further analyze the interactions of SECp43, the protein was expressed in
Escherichia coli, and small-angle X-ray scattering analysis revealed that it is a
globular protein comprising two RNA-binding domains. Using phage display, we
identified potential interaction sites and highlighted two residues (K166 and
P167) required for its dimerization. The SECp43 structural model presented here
constitutes the basis of future exploration of the protein-protein interactions
among early components of the selenocysteine biosynthesis and incorporation
pathway.
PMID- 28414461
TI - A Tetraphenylethene-Naphthyridine-Based AIEgen TPEN with Dual Mechanochromic and
Chemosensing Properties.
AB - Synthesis of new tetraphenylethene (TPE) conjugates via an innocuous route led to
the revelation of a unique TPE-based aggregation-induced emissive fluorogen 3
(TPEN), which showed an interesting mechanochromic property when the emission was
changed from blue to green upon grinding and green to blue upon fuming. The
mechanochromic property of TPEN has been explored to prepare ink-free rewritable
paper for security documentation. A detailed photophysical investigation of the
TPE-naphthyridine scaffold led to the discovery of its high sensitivity to silver
ions (Ag+) over other metal ions with a detection limit of 0.25 MUM in an aqueous
system. The stoichiometry of the complex of TPEN and silver ion was established
to be 2:1 (TPEN:Ag+) on the basis of photophysical studies, mass analysis, and
high-resolution mass spectrometry analysis.
PMID- 28414462
TI - Pyrene-Apelin Conjugation Modulates Fluorophore- and Peptide-Micelle
Interactions.
AB - Bioactive apelin peptide forms ranging in length from 12 to 55 amino acids bind
to and activate the apelin receptor (AR or APJ), a class A G-protein coupled
receptor. Apelin-12, -17, and -36 isoforms, named according to length, with an
additional N-terminal cysteine residue allowed for regiospecific and efficient
conjugation of pyrene maleimide. Through steady-state fluorescence spectroscopy,
the emission properties of pyrene in aqueous buffer were compared to those of the
pyrene-apelin conjugates both without and with zwitterionic or anionic micelles.
Pyrene photophysics are consistent with an expected partitioning into the
hydrophobic micellar cores, while pyrene-apelin conjugation prevented this
partitioning. Apelin, conversely, is expected to preferentially interact with
anionic micelles; pyrene-apelin conjugates appear to lose preferential
interaction. Finally, Forster resonance energy transfer between pyrene and
tryptophan residues in the N-terminal tail and first transmembrane segment (the
AR55 construct, comprising residues 1-55 of the AR) was consistent with efficient
nonspecific pyrene-apelin conjugate binding to micelles rather than direct,
specific apelin-AR55 binding. This approach provides a versatile fluorophore
conjugation strategy for apelin, particularly valuable given that even a highly
hydrophobic fluorophore is not deleterious to peptide behavior in membrane
mimetic micellar systems.
PMID- 28414463
TI - Do Fragments and Crystallization Additives Bind Similarly to Drug-like Ligands?
AB - The success of fragment-based drug design (FBDD) hinges upon the optimization of
low-molecular-weight compounds (MW < 300 Da) with weak binding affinities to lead
compounds with high affinity and selectivity. Usually, structural information
from fragment-protein complexes is used to develop ideas about the binding mode
of similar but drug-like molecules. In this regard, crystallization additives
such as cryoprotectants or buffer components, which are highly abundant in
crystal structures, are frequently ignored. Thus, the aim of this study was to
investigate the information present in protein complexes with fragments as well
as those with additives and how they relate to the binding modes of their drug
like counterparts. We present a thorough analysis of the binding modes of
crystallographic additives, fragments, and drug-like ligands bound to four
diverse targets of wide interest in drug discovery and highly represented in the
Protein Data Bank: cyclin-dependent kinase 2, beta-secretase 1, carbonic
anhydrase 2, and trypsin. We identified a total of 630 unique molecules bound to
the catalytic binding sites, among them 31 additives, 222 fragments, and 377 drug
like ligands. In general, we observed that, independent of the target, protein
fragment interaction patterns are highly similar to those of drug-like ligands
and mostly cover the residues crucial for binding. Crystallographic additives are
also able to show conserved binding modes and recover the residues important for
binding in some of the cases. Moreover, we show evidence that the information
from fragments and drug-like ligands can be applied to rescore docking poses in
order to improve the prediction of binding modes.
PMID- 28414464
TI - Mechanisms of Internalization of Maltose-Modified Poly(propyleneimine)
Glycodendrimers into Leukemic Cell Lines.
AB - Poly(propyleneimine) dendrimers of fourth generation partially modified with
maltose (open shell structure, PPI-m OS) have been proposed as carriers for
nucleotide anticancer drugs. The aim of this work was to provide basic insight
into interactions between fluorescently labeled PPI-m dendrimer and two distinct
leukemia cell models: CCRF-1301 lymphoid cell line and HL-60 myeloid cell line.
We applied qualitative confocal imaging and quantitative flow cytometry, as well
as trypan blue quenching and pharmacological inhibition, to investigate the
course, kinetics, and molecular mechanisms of internalization of nanoparticles.
CCRF-1301 cells take up glycodendrimer macromolecules via a relatively slow,
adsorptive endocytosis process, which is cholesterol-dependent, clathrin- and
caveolin-independent, and not followed by recycling or exocytosis. Morphological
features of this phenomenon point to the involvement of aggregation-induced cell
polarity changes (capping). In HL-60 cells, internalization is very fast,
independent of binding to the cell surface, and proceeds from the fluid phase via
a classical clathrin-dependent mechanism, ending up in an endolysosomal
compartment from which it is not further released. This substantial difference in
internalization rate and mechanism between two cell types has important
repercussions for potential application of this class of glycodendrimers as drug
delivery agents.
PMID- 28414465
TI - Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid
Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose
Tolerance.
AB - The role of the G-protein-coupled bile acid receptor TGR5 in various organs,
tissues, and cell types, specifically in intestinal endocrine L-cells and brown
adipose tissue, has made it a promising therapeutical target in several diseases,
especially type-2 diabetes and metabolic syndrome. However, recent studies have
shown deleterious on-target effects of systemic TGR5 agonists. To avoid these
systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting
enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal
permeability. In this article, we describe their synthesis, characterization, and
biological evaluation. Among them, compound 24 is a potent GLP-1 secretagogue,
has low effect on gallbladder volume, and improves glucose homeostasis in a
preclinical murine model of diet-induced obesity and insulin resistance, making
the proof of concept of the potential of topical intestinal TGR5 agonists as
therapeutic agents in type-2 diabetes.
PMID- 28414466
TI - Enantioselective Synthesis of Chiral alpha-Azido and alpha-Aryloxy Quaternary
Stereogenic Centers via the Phase-Transfer-Catalyzed alpha-Alkylation of alpha
Bromomalonates, Followed by SN2 Substitution.
AB - A new efficient synthetic method for chiral alpha-azido-alpha-alkylmalonates and
alpha-aryloxy-alpha-alkylmalonates was developed. The enantioselective alpha
alkylation of diphenylmethyl tert-butyl alpha-bromomalonate under phase-transfer
catalytic conditions [(S,S)-3,4,5-trifluorophenyl-NAS bromide, 50% KOH, toluene,
and -40 degrees C) provided the corresponding alpha-bromo-alpha-alkylmalonates
in high chemical yields (<=98%) and high optical yields (<=99% ee). The resulting
alpha-alkylated products were converted to alpha-azido-alpha-alkylmalonates
(<=96%, <=97% ee) and alpha-aryloxy-alpha-alkylmalonates (<=79%, <=93% ee) by SN2
substitution with sodium azide and aryloxides, respectively.
PMID- 28414467
TI - Variation of Bacterial Communities with Water Quality in an Urban Tropical
Catchment.
AB - A major challenge for assessment of water quality in tropical environments is the
natural occurrence and potential growth of Fecal Indicator Bacteria (FIB). To
gain a better understanding of the relationship between measured levels of FIB
and the distribution of sewage-associated bacteria, including potential
pathogens, in the tropics this study compared the abundance of FIB (Total
coliforms and E. coli) and the Bacteroidales (HF183 marker) with bacterial
community structure determined by next-generation amplicon sequencing. Water was
sampled twice over 6 months from 18 sites within a tropical urban catchment and
reservoir, followed by extraction of DNA from microorganisms, and sequencing
targeting the V3-V4 region of the 16S rRNA gene. Multivariate statistical
analyses indicated that bacterial community composition (BCC) varied between
reservoir and catchment, within catchment land-uses, and with E. coli
concentration. Beta-regression indicated that the proportion of sequences from
sewage-associated taxa (SAT) or pathogen-like sequences (PLS) were predicted most
significantly by measured levels of E. coli(log MPN/100 mL) (chi2 > 8.7; p <
0.003). In addition, SAT were significantly predicted by log HF183 levels
(chi2=13.1; p = 0.0003) while PLS were not. Our study suggests that measurements
of E. coli concentration could be useful in predicting samples enriched in sewage
associated and pathogen-like bacteria in tropical environments despite the
potential for nonconservative behavior.
PMID- 28414469
TI - Correlations between Structure and Near-Infrared Spectra of Saturated and
Unsaturated Carboxylic Acids. Insight from Anharmonic Density Functional Theory
Calculations.
AB - By near-infrared (NIR) spectroscopy and anharmonic density functional theory
(DFT) calculations, we investigate five kinds of saturated and unsaturated
carboxylic acids belonging to the group of short-chain fatty acids: propionic
acid, butyric acid, acrylic acid, crotonic acid, and vinylacetic acid. The
experimental NIR spectra of these five kinds of carboxylic acids are reproduced
by quantum chemical calculations in a broad spectral region of 7500-4000 cm-1 and
for a wide range of concentrations. By employing anharmonic GVPT2 calculations on
DFT level, a detailed interpretation of experimental spectra is achieved,
elucidating structure-spectra correlations of these molecules in the NIR region.
We emphasize the spectral features due to saturated and unsaturated alkyl chains,
the location of a C?C bond within the alkyl chain, and the dimerization of
carboxylic acids. In particular, the existence of a terminal C?C bond leads to
the appearance of highly specific NIR bands. These pronounced bands are located
at wavenumbers where no overlapping with other structure-specific bands occurs,
thus making them good structural markers. Most of the spectral differences
between these two groups of molecules remain subtle, and would be difficult to
reliably ascribe without quantum chemically calculated NIR spectra. Moreover,
anharmonic DFT calculations provide insights on the manifestation of hydrogen
bonding through distinctive spectral features corresponding to cyclic dimers. The
resulting spectral baseline elevation is common for all five investigated
carboxylic acids, and remains consistent with previous results on acetic acid.
PMID- 28414468
TI - 1,3-Dipolar Cycloaddition Reactions of Low-Valent Rhodium and Iridium Complexes
with Arylnitrile N-Oxides.
AB - The reactions between low-valent Rh(I) and Ir(I) metal-carbonyl complexes and
arylnitrile oxides possess the electronic and structural features of 1,3-dipolar
cycloadditions. Density functional theory (DFT) calculations on these reactions,
involving both cyclopentadienyl and carboranyl ligands on the metal carbonyl,
explain the ease of the chemical processes and the stabilities of the resulting
metallaisoxazolin-5-ones. The metal-carbonyl bond has partial double bond
character according to the Wiberg index calculated through NBO analysis, and so
the reaction can be considered a normal 1,3-dipolar cycloaddition involving M?C
bonds. The rates of formation of the metallacycloadducts are controlled by
distortion energy, analogous to their organic counterparts. The superior ability
of anionic Ir complexes to share their electron density and accommodate higher
oxidation states explains their calculated higher reactivity toward
cycloaddition, as compared to Rh analogues.
PMID- 28414470
TI - Association between lateral bias and personality traits in the domestic dog
(Canis familiaris).
AB - Behavioral laterality reflects the cerebral functional asymmetry. Measures of
laterality have been associated with emotional stress, problem-solving, and
personality in some vertebrate species. Thus far, the association between
laterality and personality in the domestic dog has been largely overlooked. In
this study, we investigated whether lateralized (left or right) and ambilateral
dogs differed in their behavioral response to a standardized personality test.
The dog's preferred paw to hold a Kong ball filled with food and the first paw
used to step-off from a standing position were scored as laterality measures. The
Dog Mentality Assessment (DMA) test was used to assess 5 personality traits
(e.g., sociability, aggressiveness) and a broader shy-boldness dimension. No
differences emerged between left- and right-biased dogs on any personality trait.
Instead, ambilateral dogs, scored using the Kong test, scored higher on their
playfulness (Z = -1.98, p = .048) and Aggressiveness (Z = -2.10, p = .036) trait
scores than did lateralized (irrespective of side) dogs. Also, ambilateral dogs
assessed by using the First-Stepping test scored higher than lateralized dogs on
the Sociability (Z = -2.83, p = .005) and Shy-Boldness (Z = -2.34, p = .019)
trait scores. Overall, we found evidence of a link between canine personality and
behavioral laterality, and this was especially true for those traits relating to
stronger emotional reactivity, such as aggressiveness, fearfulness, and
sociability. (PsycINFO Database Record
PMID- 28414471
TI - The reciprocal dynamic model of career decision ambiguity tolerance with career
indecision: A longitudinal three-wave investigation.
AB - The current study investigated the dynamic interplay of career decision ambiguity
tolerance and career indecision over 3 assessment times in a sample of college
students (n = 583). While the previous research has repeatedly shown an
association of career decision ambiguity tolerance with career indecision, the
direction of this association has not been adequately assessed with longitudinal
investigation. It was hypothesized in this study that there is a reciprocal
pattern of career decision ambiguity tolerance leading to subsequent career
indecision and career indecision leading to subsequent career decision ambiguity
tolerance. Using a cross-lagged panel design, this study found support for the
reciprocal pattern that aversion to ambiguity led to increased negative affect
and choice anxiety in career decision making, while negative affect and choice
anxiety led to increased aversion to ambiguity. Additionally, this study revealed
that aversion led to decreased readiness for career decision making and readiness
for career decision making led to increased interests in new information. The key
findings were discussed with respect to the theoretical and clinical implications
for career counseling along with limitations and suggestions for future research.
(PsycINFO Database Record
PMID- 28414472
TI - Disclosing a disability: Do strategy type and onset controllability make a
difference?
AB - In hiring contexts, individuals with concealable disabilities make decisions
about how they should disclose their disability to overcome observers' biases.
Previous research has investigated the effectiveness of binary disclosure
decisions-that is, to disclose or conceal a disability-but we know little about
how, why, or under what conditions different types of disclosure strategies
impact observers' hiring intentions. In this article, we examine disability onset
controllability (i.e., whether the applicant is seen as responsible for their
disability onset) as a boundary condition for how disclosure strategy type
influences the affective reactions (i.e., pity, admiration) that underlie
observers' hiring intentions. Across 2 experiments, we found that when applicants
are seen as responsible for their disability, strategies that de-emphasize the
disability (rather than embrace it) lower observers' hiring intentions by
elevating their pity reactions. Thus, the effectiveness of different types of
disability disclosure strategies differs as a function of onset controllability.
We discuss implications for theory and practice for individuals with disabilities
and organizations. (PsycINFO Database Record
PMID- 28414473
TI - An alter-centric perspective on employee innovation: The importance of alters'
creative self-efficacy and network structure.
AB - While most social network studies of employee innovation behavior examine the
focal employees' ("egos'") network structure, we employ an alter-centric
perspective to study the personal characteristics of employees' network contacts
their "alters"-to better understand employee innovation. Specifically, we examine
how the creative self-efficacy (CSE) and innovation behavior of employees' social
network contacts affects their ability to generate and implement novel ideas.
Hypotheses were tested using a sample of 144 employees in a U.S.-based product
development organization. We find that the average CSE of alters in an employee's
problem solving network is positively related to that employee's innovation
behavior, with this relationship being mediated by these alters' average
innovation behavior. The relationship between the alters' average innovation
behavior and the employee's own innovation behavior is strengthened when these
alters have less dense social networks. Post hoc results suggest that having
network contacts with high levels of CSE also leads to an increase in ego's
personal CSE 1 year later in cases where the employee's initial level of CSE was
relatively low. Implications for theory and practice are discussed. (PsycINFO
Database Record
PMID- 28414474
TI - Abstinence based incentives plus parent training for adolescent alcohol and other
substance misuse.
AB - The purpose of this study was to conduct a randomized test of clinic- and home
based incentives plus parent training for adolescent problem alcohol use.
Adolescents (N = 75) with alcohol misuse, with or without other substance misuse,
were enrolled. All youth received individual Motivational Enhancement
Therapy/Cognitive Behavior Therapy and weekly urine drug testing. The
experimental condition (EXP) included Abstinence Incentives (clinic-based
incentives for abstinence from all substances) plus weekly behavioral parent
training that included a parent-delivered, abstinence-based, substance monitoring
contract. The comparison condition (CONTROL) included Attendance Incentives
(ATTI). All adolescents met DSM-IV criteria for alcohol abuse or dependence or
reported recent binge drinking, and 77% (N = 58) met criteria for a cannabis use
disorder or had recent cannabis use at baseline. Alcohol and cannabis use
outcomes were compared across treatment conditions. A similar percentage of youth
maintained complete alcohol abstinence across the 36-week follow-up in both
conditions. However, among youth not entirely abstinent from alcohol, EXP
resulted in a lower percentage of days using alcohol during the 36 weeks after
the end of treatment than CONTROL. Among youth who also used cannabis at
baseline, results showed similar benefits of EXP on cannabis use days. Combined
individual and family based treatment, plus abstinence based incentives can
reduce substance use days during and after treatment over and above individual
evidence-based psychosocial treatment plus attendance incentives. Future research
should focus on identifying cost-effective components and incentive levels and
delivery via technology to facilitate dissemination. (PsycINFO Database Record
PMID- 28414476
TI - A socio-cultural instrumental approach to emotion regulation: Culture and the
regulation of positive emotions.
AB - We propose a sociocultural instrumental approach to emotion regulation. According
to this approach, cultural differences in the tendency to savor rather than
dampen positive emotions should be more pronounced when people are actively
pursuing goals (i.e., contexts requiring higher cognitive effort) than when they
are not (i.e., contexts requiring lower cognitive efforts), because cultural
beliefs about the utility of positive emotions should become most relevant when
people are engaging in active goal pursuit. Four studies provided support for our
theory. First, European Americans perceived more utility and less harm of
positive emotions than Japanese did (Study 1). Second, European Americans
reported a stronger relative preference for positive emotions than Asians, but
this cultural difference was larger in high cognitive effort contexts than in
moderate or low cognitive effort contexts (Study 2). Third, European Americans
reported trying to savor rather than dampen positive emotions more than Asians
did when preparing to take an exam, a typical high cognitive effort context
(Studies 3-4), but these cultural differences were attenuated when an exam was
not expected (Study 3) and disappeared when participants expected to interact
with a stranger (Study 4). These findings suggest that cultural backgrounds and
situational demands interact to shape how people regulate positive emotions.
(PsycINFO Database Record
PMID- 28414475
TI - Cognitive functioning of adolescent and young adult cannabis users in the
Philadelphia Neurodevelopmental Cohort.
AB - Cannabis use in youth is rising and has been linked to deficits in cognitive
functioning. However, cognitive findings have primarily been based on small
samples of users seeking treatment, and few studies have evaluated cognition in
occasional cannabis users. Here, we examined 4,568 adolescents and young adults
(ages 14-21 years) drawn from the Philadelphia Neurodevelopmental Cohort, a
prospective, population-based study. Participants were classified as cannabis Non
Users (n = 3,401), Occasional Users (twice per week or less; n = 940), or
Frequent Users (>3 times per week; n = 227). Mixed-model analyses examined main
effects of cannabis use and interactions between age and cannabis use on
cognitive functioning. There was a significant interaction between cannabis group
and age such that adolescent (but not young adult) Frequent Users performed worse
than Non-Users on measures of executive control (p = .002). Earlier age of
cannabis use was associated with worse performance in executive control in
Occasional Users (p = .04). Unexpectedly, Occasional Users exhibited better
executive control, memory, and social cognition than Non-Users (ps < .05).
Although mild executive control deficits in adolescent frequent users and a
relation between early cannabis initiation and cognitive performance are
partially consistent with prior research, cognitive deficits were not found in
other hypothesized domains in this community-based sample. Moreover, occasional
cannabis users displayed equivalent or even slightly better executive control,
social-cognitive, and memory abilities compared with nonusers, suggesting complex
relationships between cannabis use and cognition in youth. Longitudinal studies
with community samples are needed to identify variables affecting risk and
resilience to cognitive deficits associated with cannabis. (PsycINFO Database
Record
PMID- 28414477
TI - When ideology meets conflict-related content: Influences on emotion generation
and regulation.
AB - Do rightists and leftists experience information about suffering and harm with
differing emotional intensities, depending on the identity of target depicted? Do
they consequently choose differently how to regulate or cope with these emotions?
Research has identified ideological differences in emotional processes, but it
has yet to identify what types of content lead to ideological differences in
emotional intensity or whether these content-dependent differences relate to
differing preferences for engaging versus disengaging emotion-regulation
strategies. We posited that right-left differences in experienced emotional
intensity would be context-dependent, emerging mostly in response to depictions
of harm to the outgroup, in accordance with the centrality of intergroup
attitudes to ideological self-placement in conflict. Study 1 (N = 83) supported
this hypothesis, with leftists (vs. rightists) experiencing outgroup harm (but
not ingroup harm or conflict-irrelevant harm) with greater emotional intensity.
Study 2 (N = 101), which replicated this finding, additionally examined whether
behavioral differences in regulatory choice consequently emerge mostly regarding
outgroup harm. We tested 2 competing hypotheses as to the nature of these
differences: (a) the intensity hypothesis, positing that leftists (more than
rightists) would regulate their intensified reactions to outgroup harm through
disengagement-distraction (vs. engagement-reappraisal) due to a documented
greater preference for disengaging coping strategies as intensity increases, and
(b) the motivation hypothesis, positing that leftists (more than rightists) would
prefer engagement-reappraisal (vs. disengagement-distraction), consistent with
leftists' documented greater preference for intergroup empathy. Results
exclusively supported the intensity hypothesis, and the significance of both
studies is discussed. (PsycINFO Database Record
PMID- 28414478
TI - Enhancing effects of contingency instructions on fear acquisition and extinction
in anxiety disorders.
AB - Explicit instructions regarding stimulus-threat associations increase acquisition
and extinction of fear in healthy participants. The current study aimed to
investigate the effect of contingency instructions on fear acquisition and
extinction in patients with anxiety disorders. Patients with various anxiety
disorders (N = 104) and healthy comparison participants (N = 93) participated in
a differential fear conditioning task (within-subjects design). Approximately
halfway through the acquisition phase, participants were instructed about the
stimulus-threat association, and approximately halfway through the extinction
phase, participants were informed that the unconditioned stimulus (US) would no
longer be administered. Outcome measures were: fear-potentiated startle, skin
conductance, fearfulness ratings, and US expectancy ratings. Patients
demonstrated overall increased physiological and subjective fear responses during
acquisition and extinction phases, relative to the comparison group. There were
no major differences in fear acquisition and extinction between patients with
different anxiety disorders. During acquisition, instructions led to increased
discrimination of fear responses between a danger cue (conditioned stimulus
[CS]+) and safety cue (CS-) in both patients and comparison participants.
Moreover, instructions strengthened extinction of fear responses in the patient
and comparison group. Patients and healthy comparison participants are better
able to discriminate between danger and safety cues when they have been
explicitly informed about cues that announce a threat situation. Considering the
analogies between fear extinction procedures and exposure therapy, this suggests
that specific instructions on stimulus-threat associations during exposure
therapy might improve short-term treatment efficacy. The question remains for
future studies whether instructions have a positive effect on extinction learning
in the longer term. (PsycINFO Database Record
PMID- 28414479
TI - Group education sessions for women veterans who experienced sexual violence:
Qualitative findings.
AB - INTRODUCTION: The impact of sexual violence (SV) on mental health, self-care, and
interpersonal relationships is profound and poses special challenges to health
care delivery. Reproductive health care merits special attention because the care
required may be linked to reminders of past abuse. We explored facilitators and
barriers affecting the use of reproductive health services among women veterans
with a history of SV. METHOD: Between June and September 2015, we conducted 2
focus groups and 3 general education sessions with 27 female veterans with a
history of SV at 1 medical center. We analyzed transcripts according to applied
thematic analysis and used Nvivo software for data management and retrieval.
RESULTS: Three main themes emerged from the focus groups and education sessions.
PARTICIPANTS: (a) expressed a desire for greater agency in relation to the
control they have over their bodies and medical care; (b) described how
posttraumatic stress symptoms are retriggered during medical care; and (c)
expressed needs for additional education, peer and provider support within the
medical system. DISCUSSION: For women with a history of SV, multiple individual
and systemic barriers complicate how they utilize reproductive health services.
Group education sessions were an effective mode of support, information and
connection to other women within the Veterans Health Administration. (PsycINFO
Database Record
PMID- 28414480
TI - Fungible parameter estimates in structural equation modeling.
AB - Extending work by Waller (2008) on fungible regression coefficients, we propose a
method for computation of fungible parameter estimates in structural equation
modeling. Such estimates are defined as distinct alternative solutions for
parameter estimates, where all fungible solutions yield identical model fit that
is only slightly worse than the fit provided by optimal estimates. When such
alternative estimates are found to be highly discrepant from optimal estimates,
then substantive interpretation based on optimal estimates is called into
question. We present a computational method and 3 illustrations showing the
potential impact of this approach in applied research, and we discuss
implications and issues for further research. (PsycINFO Database Record
PMID- 28414481
TI - Word order denotes relevance differences: The case of conjoined phrases with
lexical gender.
AB - This work explores the order of linguistic references to the two genders (e.g.,
men and women vs. women and men). It argues that a gender is more likely to be
mentioned first when it is perceived to have higher relevance in a context rather
than lower relevance, and audiences assign stronger relevance to a party when the
party is mentioned first rather than second. Studies 1-3 document the current
prevalence of male-first conjoined phrases in the public (but not family) domain
and link the pattern to historical changes in women's public presence over the
20th century. Study 4 shows that contextual relevance cues affect the odds of
first mention, such that people are more likely to refer to a woman before a man,
when the two are in a primary school classroom rather than a corporate office. At
the same time, Studies 4 and 5 find that people often choose to reproduce
collectively preferred word order patterns (e.g., men and women). Studies 6 and 7
show that these choices matter because people assign more relevance to a party
when it comes first rather than second in a conjoined phrase. Overall, this work
offers theoretical grounding and empirical evidence for word order as a means of
expressing and perpetuating gender stereotypes. (PsycINFO Database Record
PMID- 28414482
TI - The power and limits of personal change: When a bad past does (and does not)
inspire in the present.
AB - Observing other people improve their lives can be a powerful source of
inspiration. Eight experiments explore the power, limits, and reasons for this
power of personal change to inspire. We find that people who have improved from
undesirable pasts (e.g., people who used to abuse extreme drugs but no longer do)
are more inspiring than people who maintain consistently desirable standings
(e.g., people who have never used extreme drugs to begin with), because change is
perceived as more effortful than stability (Experiments 1a and 1b). The
inspirational power of personal change is rooted in people's lack of access to
the internal struggles and hard work that many others may endure to successfully
remain 'always-good.' Accordingly, giving observers access into the effort
underlying others' success in maintaining consistently positive standings
restores the inspiring power of being 'always-good' (Experiments 2-4). Finally,
change is more inspiring than stability across many domains but one: people who
used to harm others but have since reformed (e.g., ex-bullies or ex-cheaters) do
not inspire, and in many cases are indeed less inspiring than people who have
never harmed others to begin with (Experiments 5-7). Together, these studies
reveal how, why, and when one's past influences one's present in the eyes of
others: having some "bad" in your past can be surprisingly positive, at least
partly because observers assume that becoming "good" is harder than being "good"
all along. (PsycINFO Database Record
PMID- 28414483
TI - Freedom of racist speech: Ego and expressive threats.
AB - Do claims of "free speech" provide cover for prejudice? We investigate whether
this defense of racist or hate speech serves as a justification for prejudice. In
a series of 8 studies (N = 1,624), we found that explicit racial prejudice is a
reliable predictor of the "free speech defense" of racist expression.
Participants endorsed free speech values for singing racists songs or posting
racist comments on social media; people high in prejudice endorsed free speech
more than people low in prejudice (meta-analytic r = .43). This endorsement was
not principled-high levels of prejudice did not predict endorsement of free
speech values when identical speech was directed at coworkers or the police.
Participants low in explicit racial prejudice actively avoided endorsing free
speech values in racialized conditions compared to nonracial conditions, but
participants high in racial prejudice increased their endorsement of free speech
values in racialized conditions. Three experiments failed to find evidence that
defense of racist speech by the highly prejudiced was based in self-relevant or
self-protective motives. Two experiments found evidence that the free speech
argument protected participants' own freedom to express their attitudes; the
defense of other's racist speech seems motivated more by threats to autonomy than
threats to self-regard. These studies serve as an elaboration of the
Justification-Suppression Model (Crandall & Eshleman, 2003) of prejudice
expression. The justification of racist speech by endorsing fundamental political
values can serve to buffer racial and hate speech from normative disapproval.
(PsycINFO Database Record
PMID- 28414484
TI - Can we "apply" the findings of Forster and Lavie (2008)? On the generalizability
of attentional capture effects under varying levels of perceptual load.
AB - Perceptual Load theory states that the degree of perceptual load on a display
determines the amount of leftover attentional resources that the system can use
to process distracting information. An important corollary of this theory is that
the amount of perceptual load determines the vulnerability of the attention
system to being captured by completely irrelevant stimuli, predicting larger
amounts of capture with low perceptual load than with high perceptual load. This
prediction was first confirmed by Forster and Lavie (2008). Here, we report 6
experiments that followed up on those earlier results, where we find that in many
cases, the opposite pattern is obtained: attentional capture increased with
increasing perceptual load. Given the lack of generalizability of the theory to
new experimental contexts with fairly minor methodological differences, we
conclude that Perceptual Load may not be a useful framework for understanding
attentional capture. The theoretical and applied importance of these findings is
discussed. In particular, we caution against using this theory in applied tasks
and settings because best-use recommendations stemming from this theory regarding
strategies to decrease distractibility may in fact produce the opposite effect:
an increase in distractibility (with distractibility being indexed by the
magnitude of the capture effect). (PsycINFO Database Record
PMID- 28414485
TI - Incentivizing attendance to prolonged exposure for PTSD with opioid use disorder
patients: A randomized controlled trial.
AB - OBJECTIVE: To determine whether contingent monetary incentives increase opioid
use disorder patients' attendance to Prolonged Exposure (PE) therapy and whether
attendance is associated with improvement in posttraumatic stress disorder (PTSD)
and substance use disorder (SUD) outcomes. METHOD: Patients (N = 58) with PTSD
were offered PE or PE with incentives (PE + I; max $480) to attend PE sessions.
Participants were assessed at baseline and weeks 6, 12, and 24 postrandomization.
RESULTS: Participants were mostly women (79%) and Caucasian (71%); mean age 37.43
years (SD = 11.33). PE + I participants attended a median of 9 (of 12) sessions
compared to 1 session for PE participants (p < .001), which included more
exposure sessions (PE + I mdn = 6; PE mdn = 0; p < .001). A Time * treatment
condition interaction indicated that PE + I participants exhibited a greater
decrease in PTSD severity over time than PE participants (OR = 3.1; 95% CI = 0.4
5.7; p = .024). PE + I participants remained in substance use treatment longer
than PE participants (mdn days = 262 vs. 192; p = .039). There were no group
differences in drug use. CONCLUSIONS: Monetary incentives increased SUD patients'
attendance to an otherwise poorly attended treatment for PTSD. Better attendance
in the incentivized group was associated with greater PTSD improvement, better
SUD treatment retention, and no increased drug use. Incentives are well supported
for improving adherence to substance use treatment goals and promising as a means
to improve therapy attendance, which may improve the effectiveness of existing
psychotherapies in difficult-to-treat populations. (PsycINFO Database Record
PMID- 28414486
TI - Girls with childhood ADHD as adults: Cross-domain outcomes by diagnostic
persistence.
AB - OBJECTIVE: To ascertain adult outcomes in 10 domains reflecting symptomatology
(internalizing, externalizing, self-injury, substance use), attainment
(education, employment), and impairment (health, social, driving, overall) as a
function of both childhood diagnosis of attention-deficit/hyperactivity disorder
(ADHD) and persistence of ADHD symptoms across time. METHOD: We prospectively
followed 140 grade-school-aged girls with rigorously diagnosed childhood ADHD and
88 age- and ethnicity-matched comparison girls for 16 years. Outcome measures
were obtained via self- and parent-report questionnaires, interviews, and
objective tests. RESULTS: Childhood ADHD, whether it remitted or persisted, was a
pernicious risk factor for a limited number of poor outcomes, including low
educational attainment, unplanned pregnancy, body mass index (BMI), and clinician
rated impairment. Childhood ADHD that persisted over time, whether completely or
partially, was associated with a number of additional detrimental outcomes in the
externalizing, internalizing, self-injury, occupational, social, and overall
impairment domains. Finally, in this all-female sample, ADHD was not associated
with objective measures of employment, substance use, or driving outcomes.
CONCLUSIONS: We discuss the considerable impairments accruing from both childhood
limited and adult-persisting ADHD, with major implications for the health and
well-being of females with this neurodevelopmental disorder. (PsycINFO Database
Record
PMID- 28414487
TI - How much is enough? Examining frequency criteria for NSSI disorder in adolescent
inpatients.
AB - OBJECTIVE: To empirically evaluate the diagnostic relevance of the proposed
Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; APA, 2013)
Criterion-A frequency threshold for nonsuicidal self-injury (NSSI) disorder.
METHOD: Archival, de-identified, self-reported clinical assessment data from 746
adolescent psychiatric patients (Mage = 14.97; 88% female; 76% White) were used.
The sample was randomly split into 2 unique samples for data analyses. Measures
included assessments of NSSI, proposed DSM-5 NSSI-disorder criteria,
psychopathology, dysfunction, distress, functional impairment, and suicidality.
RESULTS: Discriminant-function analyses run with Sample A identified a
significant differentiation of groups based on a frequency of NSSI at 25 or more
days in the past year, Lambda = .814, chi2(54) = 72.59, p < .05, canonical R2 =
.36. This cutoff was replicated in the second sample. All patients were coded
into 1 of 3 empirically derived NSSI-frequency cutoff groups: high (>25 days),
moderate (5-24 days), and low (1-4 days) and compared. The high-NSSI group scored
higher on most NSSI features, including DSM-5-proposed Criterion-B and -C
symptoms, depression, psychotic symptoms, substance abuse, borderline personality
disorder features, suicidal ideation, and suicide plans, than the moderate- and
low-NSSI groups, who did not differ from each other on many of the variables.
CONCLUSION: The currently proposed DSM-5 Criterion-A frequency threshold for NSSI
disorder lacks validity and clinical utility. The field needs to consider raising
the frequency threshold to ensure that a meaningful and valid set of diagnostic
criteria are established, and to avoid overpathologizing individuals who
infrequently engage in NSSI. (PsycINFO Database Record
PMID- 28414488
TI - An intervention for nonsuicidal self-injury in young adults: A pilot randomized
controlled trial.
AB - OBJECTIVE: Nonsuicidal self-injury (NSSI) is prevalent among young adults and
associated with negative medical and psychological consequences, necessitating
its treatment. However, few treatments have been developed to treat NSSI
specifically, or to treat the behavior among individuals without borderline
personality disorder. The purpose of this study was to investigate the Treatment
for Self-Injurious Behaviors (T-SIB), a brief, behavioral intervention
specifically developed to treat NSSI among young adults, in a pilot randomized
controlled trial (RCT). METHOD: Young adults (N = 33; age: M = 22.36 years, SD =
3.40) meeting inclusion and exclusion criteria were randomly assigned to the
treatment (T-SIB; n = 15) or treatment as usual (n = 18) condition. The sample
was 93.9% female, 42.4% Caucasian, and 30.3% Hispanic/Latino. RESULTS:
Feasibility and acceptability of the study and intervention were supported, and
medium effects were found for decreased NSSI frequency in the T-SIB group using
intent-to-treat analyses. CONCLUSION: Results of this study support the further
evaluation of T-SIB in a larger RCT. (PsycINFO Database Record
PMID- 28414489
TI - Prospective identification of adolescent suicide ideation using classification
tree analysis: Models for community-based screening.
AB - OBJECTIVE: Although a large number of risk markers for suicide ideation have been
identified, little guidance has been provided to prospectively identify
adolescents at risk for suicide ideation within community settings. The current
study addressed this gap in the literature by utilizing classification tree
analysis (CTA) to provide a decision-making model for screening adolescents at
risk for suicide ideation. METHOD: Participants were N = 4,799 youth (Mage =
16.15 years, SD = 1.63) who completed both Waves 1 and 2 of the National
Longitudinal Study of Adolescent to Adult Health. CTA was used to generate a
series of decision rules for identifying adolescents at risk for reporting
suicide ideation at Wave 2. RESULTS: Findings revealed 3 distinct solutions with
varying sensitivity and specificity for identifying adolescents who reported
suicide ideation. Sensitivity of the classification trees ranged from 44.6% to
77.6%. The tree with greatest specificity and lowest sensitivity was based on a
history of suicide ideation. The tree with moderate sensitivity and high
specificity was based on depressive symptoms, suicide attempts or suicide among
family and friends, and social support. The most sensitive but least specific
tree utilized these factors and gender, ethnicity, hours of sleep, school-related
factors, and future orientation. CONCLUSIONS: These classification trees offer
community organizations options for instituting large-scale screenings for
suicide ideation risk depending on the available resources and modality of
services to be provided. This study provides a theoretically and empirically
driven model for prospectively identifying adolescents at risk for suicide
ideation and has implications for preventive interventions among at-risk youth.
(PsycINFO Database Record
PMID- 28414490
TI - Interference and memory capacity limitations.
AB - Working memory (WM) is thought to have a fixed and limited capacity. However, the
origins of these capacity limitations are debated, and generally attributed to
active, attentional processes. Here, we show that the existence of interference
among items in memory mathematically guarantees fixed and limited capacity limits
under very general conditions, irrespective of any processing assumptions.
Assuming that interference (a) increases with the number of interfering items and
(b) brings memory performance to chance levels for large numbers of interfering
items, capacity limits are a simple function of the relative influence of
memorization and interference. In contrast, we show that time-based memory
limitations do not lead to fixed memory capacity limitations that are independent
of the timing properties of an experiment. We show that interference can mimic
both slot-like and continuous resource-like memory limitations, suggesting that
these types of memory performance might not be as different as commonly believed.
We speculate that slot-like WM limitations might arise from crowding-like
phenomena in memory when participants have to retrieve items. Further, based on
earlier research on parallel attention and enumeration, we suggest that crowding
like phenomena might be a common reason for the 3 major cognitive capacity
limitations. As suggested by Miller (1956) and Cowan (2001), these capacity
limitations might arise because of a common reason, even though they likely rely
on distinct processes. (PsycINFO Database Record
PMID- 28414491
TI - Associations between emotional abuse and neglect and dimensions of alexithymia:
The moderating role of sex.
AB - OBJECTIVE: Child maltreatment, specifically emotional maltreatment (i.e., an act,
such as belittling, blaming, or rejection, that is potentially harmful to a
child's emotional development), has emerged as an important correlate of
alexithymia. However, the evidence is mixed with regard to how emotional abuse
and neglect might relate to dimensions of alexithymia (i.e., externally oriented
thinking, difficulty describing feelings, and difficulty identifying feelings).
Furthermore, research is needed to identify individual factors that might
influence these associations. The current study examined the links between
emotional abuse and neglect and externally oriented thinking, difficulty
describing feelings, and difficulty identifying feelings and evaluated whether
sex moderated these associations. METHOD: Participants included 500 emerging
adults (49.6% male) who completed an online battery of questionnaires assessing
history of child maltreatment and dimensions of alexithymia. RESULTS: Regression
analyses revealed that emotional abuse was associated with difficulty describing
feelings and externally oriented thinking, but not difficulty identifying
feelings. Emotional neglect was associated with difficulty identifying feelings,
but not difficulty describing feelings or externally oriented thinking. There
were no sex differences associated with difficulty describing feelings or
externally oriented thinking. However, sex moderated the associations between
emotional abuse and neglect and difficulty identifying feelings such that
emotional abuse and neglect were both more strongly associated with difficulty
identifying feelings for females. CONCLUSION: These results suggest that, in the
aftermath of emotional maltreatment, sex may play an important role in the
development of difficulty identifying feelings. (PsycINFO Database Record
PMID- 28414492
TI - Measuring psychological change after trauma: Psychometric properties of a new bi
directional scale.
AB - OBJECTIVE: The current scientific measures of posttraumatic changes in the wake
of major stressors have mostly been unidirectional. This study is an attempt to
develop a scale that will capture the continuum of positive to negative
psychological changes after trauma. METHOD: Forty-five statements were presented
to a veteran sample (N = 4,053) with the request to report for each item their
experiences of negative, positive, or no posttraumatic changes as a result of
their deployment to Afghanistan. RESULTS: Principal component analysis brought
out 4 dimensions; 26 nonoverlapping items that had correlations above .40 were
selected for the final version of the scale. The 4 dimensions were given the
following designations: Self-Confidence, Interpersonal Involvement, Awareness,
and Social Adaptability. Most veterans reported positive changes (36.8-80.8%)
whereas a minority reported negative changes (4.5-22.0%). The total scale score
correlated negatively with measures of depression, anxiety, sleep disorders, and
posttraumatic stress symptoms. CONCLUSION: The posttraumatic change scale (PTCS)
demonstrated acceptable psychometric properties and captured the range from
negative to positive posttraumatic changes after major stress. Contrary to
several previous studies, positive posttraumatic change, as measured by the PTCS,
was not associated with increased symptoms of psychopathology. This underscores
the heterogeneity of psychological responses to traumatic events. (PsycINFO
Database Record
PMID- 28414493
TI - Predictors of differential PTSD treatment outcomes between veteran and civilian
women after cognitive processing therapy.
AB - OBJECTIVE: This study used data from a recent randomized clinical trial (RCT)
that found differences between women veterans and civilians in posttraumatic
stress disorder (PTSD) treatment response, with civilians demonstrating greater
improvement than did veterans. Despite having similar PTSD severity scores at
baseline, veterans scored roughly 18 points higher than civilians did on the
Clinician-Administered PTSD Scale (CAPS) at posttreatment (p < .01). This study
sought to identify the clinical and treatment variables that were associated with
the differential response to treatment demonstrated by the women in the RCT.
METHOD: Veteran (n = 21) and civilian (n = 105) women with PTSD received
cognitive processing therapy (CPT) for PTSD. These secondary data analyses used
structural equation modeling to investigate the role of 7 clinical and treatment
variables to explain the reduced treatment response to CPT in veterans compared
to civilians. RESULTS: Using structural equation modeling, we found that
differences in CAPS scores at posttreatment were largely mediated by negative
posttraumatic cognitions, as measured by the Posttraumatic Cognition Inventory
(PTCI). Although veterans and civilians had similar PTCI scores at baseline,
civilians had significantly lower PTCI scores at posttreatment, which predicted
lower CAPS scores at posttreatment. This mediation appeared to be at least in
part explained by lower treatment expectancies by veterans compared to civilians.
CONCLUSIONS: Future research should be focused on further understanding and
addressing these 2 treatment outcome predictors in an effort to reduce the gap in
PTSD treatment outcomes between veterans and civilians. (PsycINFO Database Record
PMID- 28414494
TI - Discrimination, daily stress, sleep, and Mexican-origin adolescents'
internalizing symptoms.
AB - OBJECTIVE: Using diary and longitudinal data, the current study examined the
relations between Mexican-origin youths' ethnic discrimination, daily sleep and
stress processes, and internalizing symptoms. METHOD: Adolescents (N = 113; 49.6%
female, Mage = 15.73 years) participated in an initial in-home interview and
reported on ethnic discrimination and internalizing symptoms. They then completed
a 3-day diary study and reported on their daily stress and sleep behaviors (i.e.,
sleep quality, sleep duration). Adolescents' internalizing symptoms were
reassessed 2 years after the initial assessment. RESULTS: Discrimination related
to greater daily stress and lower sleep quality. Daily stress was, in turn,
marginally related to concurrent internalizing symptoms, but not longitudinal
changes in symptoms. Sleep duration was unrelated to discrimination experiences
and concurrent and long-term internalizing symptoms. CONCLUSION: Discrimination
disrupts daily processes that include overall stress levels and sleep quality.
Daily stress processes may help explain the link between discrimination and
Mexican-origin adolescents' concurrent internalizing symptoms. Research examining
daily processes provides insight into psychological and behavioral implications
of discrimination experiences of adolescents. (PsycINFO Database Record
PMID- 28414495
TI - Racial discrimination, racial identity, and impostor phenomenon: A profile
approach.
AB - OBJECTIVES: This study examined the association between racial discrimination and
the impostor phenomenon (IP) and the moderating influence of racial identity on
this relationship. METHOD: One hundred fifty-seven African American college
students (68% female; mean age = 18.63) completed measures of racial
discrimination, racial identity, and IP during 2 waves of data collection.
RESULTS: Utilizing latent profile analyses, 4 patterns of racial identity were
identified: Undifferentiated, Multiculturalist, Race-Focused, and Humanist.
Racial discrimination predicted higher subsequent levels of IP. Racial identity
did not moderate the impact of racial discrimination; however, students in the
Multiculturalist and Humanist groups reported the lowest and highest levels of IP
at Wave 2, respectively. CONCLUSION: IP is influenced by racial discrimination
experiences as well as by the significance and meaning that individuals ascribe
to being African American. (PsycINFO Database Record
PMID- 28414496
TI - Impaired psychomotor function and plasma methadone and levo-alpha-acetylmethadol
(LAAM) concentrations in opioid-substitution patients.
AB - Tolerance to the psychomotor impairing effects of opioid drugs is expected to
develop with repeated dosing, but may be incomplete. The relationship between
plasma opioid concentration and psychomotor function in opioid-dependent patients
was examined to determine whether impairment was more likely at the time of
highest plasma drug concentration. Sixteen patients participating in a cross-over
trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times
over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs). Venous blood
was collected for the quantification of plasma (R)-(-)-methadone, LAAM, and nor
LAAM concentrations. The Digit Symbol Substitution Test (DSST) and Trail-Making
Test were administered at the time of peak plasma concentration. Ten healthy
controls (HCs) also participated. OSPAT scores (obtained for 15 patients)
fluctuated significantly across the dosing-interval for both drugs and were lower
in patients than HCs at the times of peak concentrations of (R)-(-)-methadone (1
hr: (mean difference; 95% CI) (2.13; 0.18-4.08); 2 hrs: (2.38; 0.48-4.28)
postdosing) and LAAM (2 hrs: (1.81; 0.09-3.53), and 4 hrs (1.90: 0.9-3.71)
postdosing). Within-participant analysis of the peak-change from baseline for
OSPAT scores found that 10 of the 15 patients could be categorized as impaired on
methadone and 9 on LAAM. No HCs were impaired. Patients performed worse on the
DSST and Trails-A than HCs, but not on Trails-B. Results suggest that some
patients receiving opioids long term may exhibit impairment at the time of
highest plasma drug concentration. These patients should be made aware that their
ability to undertake complex tasks may be affected. (PsycINFO Database Record
PMID- 28414498
TI - Neighing, barking, and drumming horses-object related sounds help and hinder
picture naming.
AB - The study presented here investigated how environmental sounds influence picture
naming. In a series of four experiments participants named pictures (e.g., the
picture of a horse) while hearing task-irrelevant sounds (e.g., neighing,
barking, or drumming). Experiments 1 and 2 established two findings, facilitation
from congruent sounds (e.g., picture: horse, sound: neighing) and interference
from semantically related sounds (e.g., sound: barking), both relative to
unrelated sounds (e.g., sound: drumming). Experiment 3 replicated the effects in
a situation in which participants were not familiarized with the sounds prior to
the experiment. Experiment 4 replicated the congruency facilitation effect, but
showed that semantic interference was not obtained with distractor sounds which
were not associated with target pictures (i.e., were not part of the response
set). The general pattern of facilitation from congruent sound distractors and
interference from semantically related sound distractors resembles the pattern
commonly observed with distractor words. This parallelism suggests that the
underlying processes are not specific to either distractor words or distractor
sounds but instead reflect general aspects of semantic-lexical selection in
language production. The results indicate that language production theories need
to include a competitive selection mechanism at either the lexical processing
stage, or the prelexical processing stage, or both. (PsycINFO Database Record
PMID- 28414497
TI - Dual tasking in Parkinson's disease: Cognitive consequences while walking.
AB - OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) and
exacerbate the functional limitations imposed by PD's hallmark motor symptoms,
including impairments in walking. Though much research has addressed the effect
of dual cognitive-locomotor tasks on walking, less is known about their effect on
cognition. The purpose of this study was to investigate the relation between gait
and executive function, with the hypothesis that dual tasking would exacerbate
cognitive vulnerabilities in PD as well as being associated with gait
disturbances. METHOD: Nineteen individuals with mild-moderate PD without dementia
and 13 age- and education-matched normal control adults (NC) participated.
Executive function (set-shifting) and walking were assessed singly and during
dual tasking. RESULTS: Dual tasking had a significant effect on cognition
(reduced set-shifting) and on walking (speed, stride length) for both PD and NC,
and also on stride frequency for PD only. The impact of dual tasking on walking
speed and stride frequency was significantly greater for PD than NC. Though the
group by condition interaction was not significant, PD had fewer set-shifts than
NC on dual task. Further, relative to NC, PD showed significantly greater
variability in cognitive performance under dual tasking, whereas variability in
motor performance remained unaffected by dual tasking. CONCLUSIONS: Dual tasking
had a significantly greater effect in PD than in NC on cognition as well as on
walking. The results suggest that assessment and treatment of PD should consider
the cognitive as well as the gait components of PD-related deficits under dual
task conditions. (PsycINFO Database Record
PMID- 28414499
TI - Executive and perceptual distraction in visual working memory.
AB - The contents of visual working memory are likely to reflect the influence of both
executive control resources and information present in the environment. We
investigated whether executive attention is critical in the ability to exclude
unwanted stimuli by introducing concurrent potentially distracting irrelevant
items to a visual working memory paradigm, and manipulating executive load using
simple or more demanding secondary verbal tasks. Across 7 experiments varying in
presentation format, timing, stimulus set, and distractor number, we observed
clear disruptive effects of executive load and visual distraction, but relatively
minimal evidence supporting an interactive relationship between these factors.
These findings are in line with recent evidence using delay-based interference,
and suggest that different forms of attentional selection operate relatively
independently in visual working memory. (PsycINFO Database Record
PMID- 28414500
TI - Location-coding account versus affordance-activation account in handle-to-hand
correspondence effects: Evidence of Simon-like effects based on the coding of
action direction.
AB - An increasing number of studies have shown a close link between perception and
action, which is supposed to be responsible for the automatic activation of
actions compatible with objects' properties, such as the orientation of their
graspable parts. It has been observed that left and right hand responses to
objects (e.g., cups) are faster and more accurate if the handle orientation
corresponds to the response location than when it does not. Two alternative
explanations have been proposed for this handle-to-hand correspondence effect:
location coding and affordance activation. The aim of the present study was to
provide disambiguating evidence on the origin of this effect by employing object
sets for which the visually salient portion was separated from, and opposite to
the graspable 1, and vice versa. Seven experiments were conducted employing both
single objects and object pairs as visual stimuli to enhance the contextual
information about objects' graspability and usability. Notwithstanding these
manipulations intended to favor affordance activation, results fully supported
the location-coding account displaying significant Simon-like effects that
involved the orientation of the visually salient portion of the object stimulus
and the location of the response. Crucially, we provided evidence of Simon-like
effects based on higher-level cognitive, iconic representations of action
directions rather than based on lower-level spatial coding of the pure position
of protruding portions of the visual stimuli. (PsycINFO Database Record
PMID- 28414501
TI - Spelling ability selectively predicts the magnitude of disruption in unspaced
text reading.
AB - We examined the effect of individual differences in written language proficiency
on unspaced text reading in a large sample of skilled adult readers who were
assessed on reading comprehension and spelling ability. Participants' eye
movements were recorded as they read sentences containing a low or high frequency
target word, presented with standard interword spacing, or in one of three
unsegmented text conditions that either preserved or eliminated word boundary
information. The average data replicated previous studies: unspaced text reading
was associated with increased fixation durations, a higher number of fixations,
more regressions, reduced saccade length, and an inflation of the word frequency
effect. The individual differences results provided insight into the mechanisms
contributing to these effects. Higher reading ability was associated with greater
overall reading speed and fluency in all conditions. In contrast, spelling
ability selectively modulated the effect of interword spacing with poorer
spelling ability predicting greater difficulty across the majority of sentence-
and word-level measures. These results suggest that high quality lexical
representations allowed better spellers to extract lexical units from unfamiliar
text forms, inoculating them against the disruptive effects of being deprived of
spacing information. (PsycINFO Database Record
PMID- 28414502
TI - Change in explicit and implicit motivation toward physical activity and sedentary
behavior in pulmonary rehabilitation and associations with postrehabilitation
behaviors.
AB - OBJECTIVE: The aim of this study was twofold: (a) to determine whether Theory of
Planned Behavior (TPB) variables and implicit attitudes toward physical activity
and sedentary behavior would change during a 5-week pulmonary rehabilitation (PR)
program, and (b) to investigate the relationships between behavioral intentions,
implicit attitudes, physical activity, and sedentary behavior in
postrehabilitation. DESIGN: Out of 142 patients with respiratory disease included
in this study, 119 completed 2 questionnaires measuring TPB variables with regard
to physical activity and sedentary behavior, and an Implicit Association Test
(IAT) measuring implicit attitudes toward physical activity in contrast to
sedentary behavior. The TPB questionnaires and the IAT were administered at the
beginning (Time 1) and the end of the program (Time 2). Six months after the
program (Time 3), 62 patients provided self-reported measures of their
recreational physical activity and screen-based, leisure-time sedentary behavior.
RESULTS: Over the course of pulmonary rehabilitation, perceived behavioral
control and intentions toward physical activity increased, as did social norms
and perceived behavioral control toward sedentary behavior; implicit attitudes
were also more positive toward physical activity. Implicit attitudes at the end
of PR (Time 2) were significantly associated with postrehabilitation physical
activity (Time 3). CONCLUSIONS: TPB variables toward physical activity and
sedentary behavior as well as implicit attitudes were enhanced during PR. At 6
months, implicit attitudes were significantly associated with physical activity.
These results suggest that motivation, particularly implicit attitudes, should be
targeted in future behavioral interventions in order to optimize the effects of
rehabilitation on physical activity maintenance. (PsycINFO Database Record
PMID- 28414503
TI - Parents' role in early adolescent self-injury: An application of self
determination theory.
AB - OBJECTIVE: We applied self-determination theory to examine a model whereby
perceived parental autonomy support directly and indirectly affects nonsuicidal
self-injury (NSSI) through difficulties in emotion regulation. METHOD: 639
participants (53% female) with a mean age of 13.38 years (SD = 0.51) completed
the How I Deal with Stress Questionnaire as a screener for NSSI, the Perceptions
of Parents Scale, and the Difficulties in emotion Regulation Scale. Participants
who indicated having ever hurt themselves on purpose without the intent to die (n
= 116, 66% female) were classified in the NSSI lifetime group. RESULTS: A
mediation analysis with bootstrapping procedure revealed that adolescents who
reported their parents as being less supportive of their need for autonomy were
more likely to have engaged in NSSI. Further, this relationship was partially
mediated by emotion regulation. CONCLUSION: Adolescents who do not perceive
autonomy support from their parents, have more difficulties regulating their
emotions, and may turn to NSSI as a means to cope. Clinical implications of the
findings suggest involving the family, and specifically, targeting parental
autonomy support may be beneficial when working with young adolescents who self
injure. (PsycINFO Database Record
PMID- 28414504
TI - The qualities of attachment with significant others and self-compassion protect
adolescents from non suicidal self-injury.
AB - Nonsuicidal self-injury (NSSI) is a serious public health problem. Identifying
the factors that could help prevent or reduce NSSI is important. The current
study examined the protective roles of the perceived qualities of current
attachment to significant others (i.e., mothers, fathers, and peers) and self
compassion in adolescent NSSI. The potential mediating effect of self-compassion
in the relationships between attachment relationships with mothers, fathers, and
peers and adolescent NSSI was also explored. Self-reported data on mother,
father, and peer attachment (each included 3 dimensions; i.e., trust,
communication, and closeness); self-compassion; and NSSI were collected from 658
secondary school students (59.9% male; Mage = 13.58 years). Participants with
NSSI experiences scored significantly higher on the perceived qualities of
current attachment with parents and self-compassion than those reporting no NSSI
experience. Attachment with peers did not distinguish the NSSI group from the Non
NSSI group. Further mediation analyses indicated that self-compassion mediated
the relationships of closeness with mothers, fathers (partially), and peers to
NSSI as well as the relationship of peer communication to NSSI. Limitations of
this study and implications regarding the protective roles of attachment and self
compassion in the prevention and intervention for NSSI are discussed. (PsycINFO
Database Record
PMID- 28414505
TI - School response to self-injury: Concerns of mental health staff and parents.
AB - Nonsuicidal self-injury (NSSI) among adolescents poses a significant problem for
schools, adolescents, and their families. However, appropriate guidelines for
addressing NSSI, including when to disclose the behavior to parents, are
currently lacking. The present study aimed to understand how school mental health
staff and parents of secondary school students view NSSI to determine how parent
school communication about NSSI, and responses to NSSI, can be improved. Nineteen
school mental health staff participated in interviews and 10 parents of
adolescents with a history of NSSI completed open-ended questionnaire items.
Staff identified that sector-wide NSSI policy and education for teachers and
principals would help them feel more supported and improve consistency in
addressing NSSI between and within schools. In contrast, parents wanted more
support directed at them rather than solely their adolescent. Implications for
policy and parental support provided by the school are discussed. (PsycINFO
Database Record
PMID- 28414506
TI - Social validity of the Social Skills Improvement System-Classwide Intervention
Program (SSIS-CIP) in the primary grades.
AB - The purpose of this study was to examine the social validity of the Social Skills
Improvement System-Classwide Intervention Program (SSIS-CIP) for teachers in the
primary grades. Participants included 45 first and second grade teachers who
completed a 16-item social validity questionnaire during each year of the SSIS
CIP efficacy trial. Findings indicated that teachers generally perceived the SSIS
CIP as a socially valid and feasible intervention for primary grades; however,
teachers' ratings regarding ease of implementation and relevance and sequence
demonstrated differences across grade levels in the second year of
implementation. (PsycINFO Database Record
PMID- 28414507
TI - The distinction between exclusivity and comorbidity within NSSI.
AB - Based on notions posited by problem behavior theory, the primary goal of the
current study was to examine the possibility that adolescents who engage in NSSI
are not a homogeneous group but are rather divided into 2 subgroups: (a)
adolescents who exclusively engage in NSSI, and (b) adolescents who are involved
in NSSI alongside other problem behaviors (e.g., drug abuse, unprotected sexual
intercourse). Participants were a school sample of 436 adolescents from 6 high
schools across Israel, who completed self-report questionnaires during school
hours on engagement in NSSI and other problem behaviors, self-esteem, self
criticism, ego clarity, coping strategies, self-efficacy to regulate affect, and
sociodemographic information. Findings indicated that 22% of the sample reported
engaging in NSSI. Adolescents who reported engaging in NSSI had higher prevalence
rates of involvement in other problem behaviors compared to those who did not
report engaging in NSSI. However, a comparison between those who exclusively
engaged in NSSI and those who were involved in NSSI alongside other problem
behaviors indicated that lower ego clarity, lower self-esteem, and poorer self
efficacy to regulate affect, alongside higher self-criticism and greater use of
disengagement coping mechanisms characterized exclusive engagement in NSSI.
Distinct theoretical models are needed to characterize different forms of NSSI:
NSSI, which is an exclusive and singular phenomenon, for which problems related
to the self are prominent, versus NSSI, which is accompanied by other problem
behaviors. Accordingly, the implications related to school psychologists' work in
the assessment, treatment, and prevention of NSSI are suggested. (PsycINFO
Database Record
PMID- 28414508
TI - Dissociating affective and semantic valence.
AB - We examined the possible dissociation between two modes of valence: affective
valence (valence of e emotional response) and semantic valence (stored knowledge
about valence of an object or event). In Experiment 1, 50 participants viewed
affective pictures that were repeatedly presented while their facial
electromyography (EMG) activation and heart rate response were continuously
recorded. Half of the participants provided self-report ratings about the valence
of their feelings and half about the valence of the stimulus. Next, all
participants performed an affective Simon task. In Experiment 2, 30 new
participants performed the affective Simon task with the repeated exposure
embedded within the task. The results showed that measures related to affective
valence (feelings-focused self-reports, heart rate, and facial EMG activations)
attenuated with repeated exposure to pleasant and unpleasant pictures, whereas
measures related to semantic valence (knowledge-focused self-reports and
congruency effect of affective Simon task) did not. These findings strongly
suggest that affective and semantic valence represent two distinct psychological
constructs. (PsycINFO Database Record
PMID- 28414509
TI - Sleep and cognitive functioning in childhood: Ethnicity, socioeconomic status,
and sex as moderators.
AB - We examined children's sleep at age 9 as a predictor of developmental
trajectories of cognitive performance from ages 9 to 11 years. The effects of
sleep on cognition are not uniform and thus we tested race/ethnicity,
socioeconomic status (SES), and sex as moderators of these associations. At the
first assessment, 282 children aged 9.44 years (52% boys, 65% European American
[EA], 35% African American [AA]) participated. Two more waves of data collection
spaced 1 year apart followed. The majority of children (63%) were living at or
below the poverty line. Children's sleep was measured objectively with actigraphy
and 2 well-established sleep parameters were derived: duration, indexed by sleep
minutes between sleep onset and wake time, and quality, indexed by efficiency.
Multiple cognitive functioning domains were examined with the Woodcock Johnson
Tests of Cognitive Abilities (WJ III). Across the sample, higher sleep
efficiency, but not duration, was associated with better cognitive performance.
Significant moderation effects emerged. Controlling for SES, AA children scored
lower on general intellectual ability and working memory (WM) at age 11 only if
they experienced lower sleep efficiency at age 9. Further, boys scored lower on
general abilities and processing speed (PS) at age 11 only if their sleep
efficiency was lower at age 9. Findings indicate that lower sleep efficiency may
contribute to lower cognitive functioning especially for AA children and boys.
These vulnerabilities appear to emerge early in development and are maintained
over time. Results underscore the importance of individual differences in
explicating relations between sleep and children's cognitive performance.
(PsycINFO Database Record
PMID- 28414510
TI - A longitudinal person-centered perspective on youth social support: Relations
with psychological wellbeing.
AB - Past research suggests that perceived social support from parents, teachers, and
peers are all positively associated with wellbeing during adolescence. However,
little longitudinal research has examined the implications of distinctive
combinations of social support for developing adolescents. To address this
limitation, we measured multiple dimensions of social support, psychological ill
health, and wellbeing in a sample of 2034 Australian adolescents (Mage = 13.7;
49.6% male) measured in Grades 8 and 11. Latent transition analyses identified a
6-profile solution for both waves of data, and revealed substantial inequality in
perceived social support. Two "socially rich" profiles corresponded to 7% of the
sample and had high social support (>1SD above sample mean) from at least two
sources. (Fully Integrated; Parent and Peer Supported). In contrast, 25% of the
sample was "socially poor," having support that was between -.65 to -.86 SD below
the sample mean for all 3 sources (Isolated profile). None of the other profiles
(Peer Supported; Moderately Supported; Weakly Supported) had levels of support
below -.37 SD from any source. Furthermore, almost all wellbeing problems were
concentrated in the Isolated Profile, with negative effects more pronounced in
Grade 11 than Grade 8. Despite feeling low parent and teacher support,
adolescents in the Peer Supported profile felt strong peer support and average to
above-average levels of wellbeing in Grades 8 and 11. However, they also had an
81% chance of making a negative transition to either the Isolated or Weakly
Supported profiles in Grade 11. (PsycINFO Database Record
PMID- 28414511
TI - Change in attachment predicts change in emotion regulation particularly among 5
HTTLPR short-allele homozygotes.
AB - In view of the theory that the attachment relationship provides a foundation for
the development of emotion regulation, here, we evaluated (a) whether change in
attachment security from 4 to 6 years predicts change in emotion regulation from
6 to 8 years and (b) whether 5-HTTLPR moderates this relation in a Norwegian
community sample (n = 678, 99.7% Caucasian). Attachment was measured with the
Manchester Child Attachment Story Task, and teachers completed the Emotion
Regulation Checklist. Attachment security was modestly stable, with children
becoming more secure over time. Regression analyses revealed that increased
attachment security from 4 to 6 forecasted increases in emotion regulation from 6
to 8 and decreased attachment security forecasted decreases in emotion
regulation. This effect was strongest among the 5-HTTLPR short-allele homozygotes
and, according to competitive model fitting, in a differential-susceptibility
manner. (PsycINFO Database Record
PMID- 28414512
TI - Adolescents' intergenerational narratives across cultures.
AB - Adolescents' intergenerational narratives-the stories they tell about their
mothers' and fathers' early experiences-are an important component of their
identities (Fivush & Merrill, 2016; Merrill & Fivush, 2016). This study explored
adolescents' intergenerational narratives across cultures. Adolescents aged 12 to
21 from 3 cultural groups in New Zealand (Chinese: n = 88; Maori: n = 91;
European: n = 91) narrated stories about their mothers' and fathers' childhood
experiences. In these narratives, New Zealand Chinese and Maori adolescents
included more identity connections (statements linking their own identities to
their parents' experiences) than did New Zealand European adolescents, and New
Zealand Chinese adolescents' intergenerational narratives were more coherent than
were New Zealand European and Maori adolescents' narratives. New Zealand Chinese
and Maori adolescents were also more likely to report didactic reasons for their
mothers' telling of the narratives, whereas New Zealand European adolescents were
more likely to report reasons of sharing family history. Across cultures, but
only in their mother narratives, adolescent girls included more references to
subjective perspectives (emotions, evaluations, and cognitions) than did
adolescent boys. Older adolescents also used more subjective perspective terms
than younger adolescents. These findings suggest that intergenerational
narratives serve different functions when adolescents across cultures explore
their identities. These narratives may be especially important for adolescents
growing up in cultures with an interdependent orientation. (PsycINFO Database
Record
PMID- 28414513
TI - Civic purpose in late adolescence: Factors that prevent decline in civic
engagement after high school.
AB - This study investigated the effects of internal and demographic variables on
civic development in late adolescence using the construct civic purpose. We
conducted surveys on civic engagement with 480 high school seniors, and surveyed
them again 2 years later. Using multivariate regression and linear mixed models,
we tested the main effects of civic purpose dimensions (beyond-the-self
motivation, future civic intention), ethnicity, and education on civic
development from Time 1 to Time 2. Results showed that while there is an overall
decrease in civic engagement in the transition out of high school, both internal
and social factors protected participants from steep civic decline. Interaction
effects varied. Ethnicity and education interacted in different ways with the
dimensions of civic purpose to predict change in traditional and expressive
political engagement, and community service engagement. (PsycINFO Database Record
PMID- 28414514
TI - Pickering emulsions in foods - opportunities and limitations.
AB - In order to critically discuss the potential of Pickering-type emulsions in food
applications this review provides the theoretical background of the stabilizing
mechanisms, the resulting requirements for particles to stabilize these systems
and the limitations resulting from these fundamental considerations. Food grade
particle systems investigated in the past are presented. It becomes obvious that
with a proper choice of a particle type, oil-in-water as well as water-in-oil
emulsions can be achieved. For highly viscous products, products with a high
internal phase volume and foams Pickering particles offer alternatives to
commonly used surfactants. Pickering emulsions might be able to offer new
approaches for fat reduction as well as encapsulation and sustained release of
active ingredients. Nevertheless, a major part of successful systems have been
achieved with silica or modified silica particles, which is not in line with the
consumer demand for clean label, natural systems or not even food grade. However,
the intriguing possibilities motivate and justify future research on the
identification of new suitable ingredients, improvement of existing formulations
and identification of new fields of application.
PMID- 28414516
TI - Effects of Having Preterm Infants Smell Amniotic Fluid, Mother's Milk, and
Mother's Odor During Heel Stick Procedure on Pain, Physiological Parameters, and
Crying Duration.
AB - OBJECTIVE: The study aims to assess effects of having preterm infants smell
amniotic fluid, mother's milk, and mother's odor during heel stick procedure on
pain, physiological parameters, and crying duration. MATERIALS AND METHODS: The
study was a randomized controlled experimental research. The population of the
study was made up of preterm infants receiving treatment and care at a neonatal
intensive care unit, where the study was conducted between January 2015 and March
2016. The study was performed with 85 preterm infants who met the selection
criteria. Infants were randomized into four groups: amniotic fluid, mother's
milk, mother's odor, and control group. Data obtained were analyzed by percentage
distributions, means, standard deviation, chi-square test, Kruskal-Wallis, and
Dunnett's test. RESULTS: While no significant difference was found between the
groups in terms of total preterm infant pain profile score before, during, and
after the heel stick procedure (p > 0.05), a significant difference was found in
terms of SO2 values (p < 0.05) and the difference was caused by the amniotic
fluid group. Although no significant difference was found between the groups in
terms of crying duration (p > 0.05), the amniotic fluid group had the lowest
score, followed by the mother's milk group, the mother's odor group, and the
control group. CONCLUSIONS: Amniotic fluid, mother's milk, and mother's odor were
not effective in preterm infants during painful procedures.
PMID- 28414515
TI - Zseq: An Approach for Preprocessing Next-Generation Sequencing Data.
AB - Next-generation sequencing technology generates a huge number of reads (short
sequences), which contain a vast amount of genomic data. The sequencing process,
however, comes with artifacts. Preprocessing of sequences is mandatory for
further downstream analysis. We present Zseq, a linear method that identifies the
most informative genomic sequences and reduces the number of biased sequences,
sequence duplications, and ambiguous nucleotides. Zseq finds the complexity of
the sequences by counting the number of unique k-mers in each sequence as its
corresponding score and also takes into the account other factors such as
ambiguous nucleotides or high GC-content percentage in k-mers. Based on a z-score
threshold, Zseq sweeps through the sequences again and filters those with a z
score less than the user-defined threshold. Zseq algorithm is able to provide a
better mapping rate; it reduces the number of ambiguous bases significantly in
comparison with other methods. Evaluation of the filtered reads has been
conducted by aligning the reads and assembling the transcripts using the
reference genome as well as de novo assembly. The assembled transcripts show a
better discriminative ability to separate cancer and normal samples in comparison
with another state-of-the-art method. Moreover, de novo assembled transcripts
from the reads filtered by Zseq have longer genomic sequences than other tested
methods. Estimating the threshold of the cutoff point is introduced using
labeling rules with optimistic results.
PMID- 28414517
TI - Internet Addiction, Psychological Distress, and Coping Responses Among
Adolescents and Adults.
AB - As Internet use grows, so do the benefits and also the risks. Thus, it is
important to identify when individuals' Internet use is problematic. In the
present study, 449 participants aged from 16 to 71 years of age were sourced from
a wide range of English-speaking Internet forums, including social media and self
help groups. Of these, 68.9% were classified as nonproblematic users, 24.4% as
problematic users, and 6.7% as addictive Internet users. High use of discussion
forums, high rumination levels, and low levels of self-care were the main
contributing factors to Internet addiction (IA) among adolescents. For adults IA
was mainly predicted through engagement in online video gaming and sexual
activity, low email use, as well as high anxiety and high avoidant coping.
Problematic Internet users scored higher on emotion and avoidance coping
responses in adults and higher on rumination and lower on self-care in
adolescents. Avoidance coping responses mediated the relationship between
psychological distress and IA. These findings may assist clinicians with
designing interventions to target different factors associated with IA.
PMID- 28414518
TI - Advanced synchrotron-based and globar-sourced molecular (micro) spectroscopy
contributions to advances in food and feed research on molecular structure,
mycotoxin determination, and molecular nutrition.
AB - Mycotoxin contamination has been a worldwide problem for food and feeds
production for a long time. There is an obviously increased focus of the food and
feed industry toward the reduction of mycotoxin concentration in both the raw
materials and finished products. Therefore, both effective qualitative and
quantitative techniques for the determination of mycotoxins are required to
minimize their harmful effects. Conventional wet chemical methods usually are
time-consuming, expensive, and rely on complex extraction and cleanup
pretreatments. Synchrotron-based and globar-based molecular spectroscopy have
shown great potential to be developed as rapid and nondestructive tools for the
determination of molecular structure, molecular nutrition and mycotoxins in feed
and food. This article reviews the common types of mycotoxins in feed and food,
their toxicity, as well as the conventional detection methods. The principle of
advanced molecular spectroscopy techniques and their application prospects for
mycotoxin detection are discussed. Recent progress in food and feed research with
molecular spectroscopy techniques is highlighted. This review provides a
potential and insight into how to determine the structure and mycotoxins of feed
and food on a molecular basis with advanced Synchrotron-based and globar-based
molecular (micro) spectroscopy.
PMID- 28414519
TI - Effect of a Food Supplement Containing L-Methionine on Urinary Tract Infections
in Pregnancy: A Prospective, Multicenter Observational Study.
AB - OBJECTIVE: Adjuvants or alternatives to antibiotics in urinary tract infections
(UTIs) during pregnancy seem advisable because of possible fetal stress. The
present study assessed the effectiveness of a food supplement containing L
methionine and Hibiscus sabdariffa L. and Boswellia serrata Roxb. extracts as a
treatment for symptomatic UTIs in pregnancy. DESIGN: Pregnant patients with
symptomatic cystitis were screened for UTIs in three different clinical centers.
Those unwilling to take antibiotics were offered two alternative treatments: (A)
a 1-week treatment with the food supplement or (B) a week in which they were
advised to increase their fluid consumption to more than 1.5 L daily. After 1
week, group B patients who still had positive urine cultures (UCs) or had no UC
performed took the food supplement for an additional week. UCs were performed on
all patients at the first visit (w0) and on most of them at 7 days (w1). Patients
who were still positive at w1 or had no UC performed at w1 had UC performed 14
days (w2) thereafter. RESULTS: Of 264 pregnant women enrolled, 216 joined group
A, while 48 joined group B. At w1, 70.0% of group A patients and 43.2% of those
in group B had negative UCs (p = 0.003). The reduction of bacterial load was
42.2% +/- 8.0% and 4.5% +/- 9.2%, respectively (p < 0.0001). At w1, symptoms
disappeared in 135 patients (62.5%) in group A and 22 patients (45.8%) in group B
(p = 0.03). At w2, 30 of 32 group B patients who switched to taking the
supplement for the second week had negative UCs, including 20 who had been
positive at w1. At w2, all group A patients had negative UCs. No side effects
were reported. CONCLUSIONS: The food supplement provided effective treatment and
might be an adjuvant or alternative to antibiotic therapy of symptomatic UTI in
pregnancy.
PMID- 28414520
TI - Rare Genetic Variants in PARN Are Associated with Pulmonary Fibrosis in Families.
PMID- 28414521
TI - Representations of Search Spaces in the Problem of Mutational Pressure
Optimization According to Protein-Coding Sequences.
AB - The proper representation of the search space is the fundamental step in every
optimization task, because it has a decisive impact on the quality of potential
solutions. In particular, this problem appears when the search spaces are
nonstandard and complex, with the large number of candidate solutions that differ
from classical forms usually investigated. One of such spaces is the set of
continuous-time, homogenous, and stationary Markov processes. They are commonly
used to describe biological phenomena, for example, mutations in DNA sequences
and their evolution. Because of the complexity of these processes, the
representation of their search space is not an easy task but it is important for
effective solving of the biological problems. One of them is optimality of
mutational pressure acting on protein-coding sequences. Therefore, we described
three representations of the search spaces and proposed several specific
evolutionary operators that are used in evolutionary-based optimization
algorithms to solve the biological problem of mutational pressure optimality. In
addition, we gave a general formula for the fitness function, which can be used
to measure the quality of potential solutions. The structures of these solutions
are based on two models of DNA evolution described by substitution-rate matrices,
which are commonly used in phylogenetic analyzes. The proposed representations
have been successfully utilized in various issues, and the obtained results are
very interesting from a biological point of view. For example, they show that
mutational pressures are, to some extent, optimized to minimize cost of amino
acid substitutions in proteins.
PMID- 28414522
TI - A Comparison of Breast Milk and Sucrose in Reducing Neonatal Pain During Eye Exam
for Retinopathy of Prematurity.
AB - BACKGROUND: This double-blind randomized controlled experimental study aimed to
determine the effects of breast milk and sucrose in reducing pain in preterm
infants during retinopathy of prematurity (ROP) examination. MATERIALS AND
METHODS: This study was conducted with 60 preterm infants (breast milk group =
20, sucrose group = 20, and control/distilled water group = 20) meeting the
inclusion criteria. The data were collected with the use of an Infant Evaluation
Form, Procedure Monitoring Form, and Premature Infant Pain Profile (PIPP). The
preterm infants were provided with 1 mL of breast milk, sucrose, and distilled
water before the ROP examination. The pain level in preterm infants was measured
by the PIPP 5 minutes before, during, and 5 minutes after the ROP examination.
The ROP examinations were video recorded, and videos were evaluated by three
observers blinded to the study. RESULTS: No significant difference was determined
between the three groups in terms of their postconceptional and postnatal ages,
their body weights at birth and during the ROP examination. The PIPP scores of
the preterm infants in the three groups were higher during the ROP examination
and were not significantly different. The PIPP scores of the control group were
significantly higher than those in the breast milk and sucrose groups after the
ROP examination (p < 0.001). The preterm infants in the breast milk group
recovered and returned to their initial values more quickly after the ROP
examination than the infants in the sucrose group. CONCLUSION: To reduce pain in
preterm infants during ROP examination, breast milk is recommended.
PMID- 28414523
TI - Presence of Toxoplasma gondii in Drinking Water from an Endemic Region in
Southern Mexico.
AB - Toxoplasmosis can be acquired through the ingestion of contaminated drinking
water with oocysts of Toxoplasma gondii, highly resistant to the routinely
disinfection processes; based on chlorination commonly used in the water supply
industry. The aim of this study was to determine the presence of T. gondii DNA in
samples of public drinking water from an endemic region of southern Mexico. In
total 74 samples of water (5 L each) were collected from the three well fields
(I, II, and III) and 71 independent wells, distributing public drinking water to
the city of Merida Yucatan, after passing through the chlorination process. Water
samples were filtered and concentrated by a sucrose solution, then DNA was
extracted and evaluated through a nested-PCR (nPCR) specific for T. gondii.
Positive samples were detected in 5.4% (4/74) of the water samples. This is the
first report of the presence of T. gondii DNA in public drinking water from a
large city in southern Mexico, where their consumption without any
postpurification treatment could pose a risk for acquiring the infection in the
urban population.
PMID- 28414525
TI - Influence of physical and biological variability and solution methods in fruit
and vegetable quality nondestructive inspection by using imaging and near
infrared spectroscopy techniques: A review.
AB - Over the past decades, imaging and spectroscopy techniques have been rapidly
developing and widely applied in nondestructive fruit and vegetable quality
assessment. The physical properties (including size, shape, color, position, and
temperature) and biological properties (including cultivar, season, maturity
level and geographical origin) of fruits and vegetables vary from one to another.
A great variety of physical and biological properties of agricultural products
influence the optical propagation properties and interaction behaviors with
incident light, thus decreasing the quality inspection accuracy. Many attempts
have been made in image correction and spectral compensation methods to improve
the inspection accuracy. This paper gives a detailed summary about influence of
physical and biological variability, as well as the correction and compensation
methods for eliminating or reducing the effects in fruit and vegetable quality
nondestructive inspection by using imaging and spectroscopy techniques. The
advantages and disadvantages of the solution methods are discussed and
summarized. Additionally, the future challenges and potential trends are also
reported.
PMID- 28414526
TI - Assessing the Impact of Assemblers on Virus Detection in a De Novo Metagenomic
Analysis Pipeline.
AB - Applying high-throughput sequencing to pathogen discovery is a relatively new
field, the objective of which is to find disease-causing agents when little or no
background information on disease is available. Key steps in the process are the
generation of millions of sequence reads from an infected tissue sample, followed
by assembly of these reads into longer, contiguous stretches of nucleotide
sequences, and then identification of the contigs by matching them to known
databases, such as those stored at GenBank or Ensembl. This technique, that is,
de novo metagenomics, is particularly useful when the pathogen is viral and
strong discriminatory power can be achieved. However, recently, we found that
striking differences in results can be achieved when different assemblers were
used. In this study, we test formally the impact of five popular assemblers
(MIRA, VELVET, METAVELVET, SPADES, and OMEGA) on the detection of a novel virus
and assembly of its whole genome in a data set for which we have confirmed the
presence of the virus by empirical laboratory techniques, and compare the overall
performance between assemblers. Our results show that if results from only one
assembler are considered, biologically important reads can easily be overlooked.
The impacts of these results on the field of pathogen discovery are considered.
PMID- 28414524
TI - A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease. An
International Working Group Perspective.
PMID- 28414528
TI - A Note from the Publisher.
PMID- 28414529
TI - Introduction Arthur D. Smith, MD: Humility, Hard Work, and Grace.
PMID- 28414527
TI - Advantages and limitations of in vitro and in vivo methods of iron and zinc
bioavailability evaluation in the assessment of biofortification program
effectiveness.
AB - Biofortification aims to improve the micronutrient concentration of staple food
crops through the best practices of breeding and modern biotechnology. However,
increased zinc and iron concentrations in food crops may not always translate
into proportional increases in absorbed zinc (Zn) and iron (Fe). Therefore,
assessing iron and zinc bioavailability in biofortified crops is imperative to
evaluate the efficacy of breeding programs. This review aimed to investigate the
advantages and limitations of in vitro and in vivo methods of iron and zinc
bioavailability evaluation in the assessment of biofortification program
effectiveness. In vitro, animal and isotopic human studies have shown high iron
and zinc bioavailability in biofortified staple food crops. Human studies provide
direct knowledge regarding the effectiveness of biofortification, however, human
studies are time consuming and are more expensive than in vitro and animal
studies. Moreover, in vitro studies may be a useful preliminary screening method
to identify promising plant cultivars, however, these studies cannot provide data
that are directly applicable to humans. None of these methods provides complete
information regarding mineral bioavailability, thus, a combination of these
methods should be the most appropriate strategy to investigate the effectiveness
of zinc and iron biofortification programs.
PMID- 28414530
TI - Hope Amidst Horror: Documenting the Effects of the "War On Drugs" Among Female
Sex Workers and Their Intimate Partners in Tijuana, Mexico.
AB - Sensationalistic media coverage has fueled stereotypes of the Mexican border city
of Tijuana as a violent battleground of the global drug war. While the drug war
shapes health and social harms in profoundly public ways, less visible are the
experiences and practices of hope that forge communities of care and represent
more private responses to this crisis. In this article, we draw on ethnographic
fieldwork and photo elicitation with female sex workers who inject drugs and
their intimate, non-commercial partners in Tijuana to examine the personal
effects of the drug war. Drawing on a critical phenomenology framework, which
links political economy with phenomenological concern for subjective experience,
we explore the ways in which couples try to find hope amidst the horrors of the
drug war. Critical visual scholarship may provide a powerful alternative to
dominant media depictions of violence, and ultimately clarify why this drug war
must end.
PMID- 28414531
TI - A System Architecture for Efficient Transmission of Massive DNA Sequencing Data.
AB - The DNA sequencing data analysis pipelines require significant computational
resources. In that sense, cloud computing infrastructures appear as a natural
choice for this processing. However, the first practical difficulty in reaching
the cloud computing services is the transmission of the massive DNA sequencing
data from where they are produced to where they will be processed. The daily
practice here begins with compressing the data in FASTQ file format, and then
sending these data via fast data transmission protocols. In this study, we
address the weaknesses in that daily practice and present a new system
architecture that incorporates the computational resources available on the
client side while dynamically adapting itself to the available bandwidth. Our
proposal considers the real-life scenarios, where the bandwidth of the connection
between the parties may fluctuate, and also the computing power on the client
side may be of any size ranging from moderate personal computers to powerful
workstations. The proposed architecture aims at utilizing both the communication
bandwidth and the computing resources for satisfying the ultimate goal of
reaching the results as early as possible. We present a prototype implementation
of the proposed architecture, and analyze several real-life cases, which provide
useful insights for the sequencing centers, especially on deciding when to use a
cloud service and in what conditions.
PMID- 28414532
TI - From the Editor-in-Chief's Desk.
PMID- 28414533
TI - Lithium and Heart Block in an Adolescent Boy.
PMID- 28414534
TI - Deprescribing to improve care.
PMID- 28414535
TI - Controlling the controllable in community palliative care.
PMID- 28414536
TI - Spring has officially sprung.
PMID- 28414537
TI - Developing a caseload classification tool for community nursing.
AB - Acuity and dependency in the community nursing caseload in combination with safe
staffing levels are a national issue of concern. Current evidence suggests that
there are no clear approaches to determining staff capacity and skill mix in
these community settings. As community nursing caseloads are large with differing
complexities, there is a need to allocate community nursing with the best skill
mix to achieve the best patient outcomes. A city-wide service improvement
initiative developed a tool to classify and categorise patient demand and this
was linked to an electronic patient record system. The aim was to formulate an
effective management response to different levels of acuity and dependency within
community nursing teams and a consensus approach was used to allow the definition
of complexity for twelve packages of care. The tool was piloted by a group of
community nurses to assess the validity as a method to achieve a caseload
classification. Seventy nurses were trained and applied the tool to 3000 patient
referrals. Based on this, standards of care were agreed including expectations of
assessment, intervention, visit length and frequency. Community nursing caseloads
can now be organised according to acuity and complexity of patient need, which
determines allocation of staff and skill mix.
PMID- 28414538
TI - Part 3: Impact of systemic conditions and medications on oral health.
AB - The people who are treated in the community setting will often have multiple
comorbidities. Systemic medical conditions can have a negative impact on oral
health. In addition, the medications used to treat systemic conditions may also
themselves cause oral symptoms. As a large proportion of patients treated by the
community nursing team will be elderly, this paper will focus on common geriatric
conditions that can display oral or dental symptoms. The effects of medications
will be discussed and linked to oral complaints patients may express. The primary
aims are to give a broad overview of the oral effects of ageing, of illness and
of polypharmacy and advise on how these can be best managed by the nursing team.
PMID- 28414539
TI - Sleep and dementia.
PMID- 28414540
TI - The future of community nursing: Hospital in the Home.
AB - With an increasing ageing population who often have multiple long-term
conditions, there is a growing need to provide an alternative type of care to the
traditional hospital-based model. 'Hospital in the Home' is a model that provides
integrated care for patients in their home. The @home service was established in
2013 by Guy's and St Thomas' NHS Foundation Trust. The service provides health
care in patients' home, supporting early discharge from hospital as well as
preventing avoidable admissions and readmissions saving valuable hospital bed
days and reducing length of stay. This article describes the service available
with the use of a case study of a 78-year-old lady who was referred by the London
Ambulance Service with exacerbation of chronic obstructive pulmonary disease
(COPD). This case study highlights the ability to assess, treat and manage an
acutely unwell patient with newly diagnosed heart failure in the community
without the need for hospitalisation. This type of integrated care model with a
multidisciplinary team is a feasible alternative to the traditional models of
care in both the acute and community settings.
PMID- 28414541
TI - Stoma care: an update on current guidelines for community nurses.
PMID- 28414542
TI - Revisiting constipation management in the community.
PMID- 28414543
TI - Private deprivation of liberty.
AB - The Court of Appeal has ruled that a person is deprived of their liberty in their
own home even though care and treatment was provided in the person's own home and
funded using the person's money. In this article Richard Griffith discusses when
a private deprivation of liberty must be authorised by a welfare order from the
Court of Protection.
PMID- 28414544
TI - Part 2: Assessing foot risk status and points of action.
PMID- 28414545
TI - Modular use of human body models of varying levels of complexity: Validation of
head kinematics.
AB - OBJECTIVE: The significant computational resources required to execute detailed
human body finite-element models has motivated the development of faster running,
simplified models (e.g., GHBMC M50-OS). Previous studies have demonstrated the
ability to modularly incorporate the validated GHBMC M50-O brain model into the
simplified model (GHBMC M50-OS+B), which allows for localized analysis of the
brain in a fraction of the computation time required for the detailed model. The
objective of this study is to validate the head and neck kinematics of the GHBMC
M50-O and M50-OS (detailed and simplified versions of the same model) against
human volunteer test data in frontal and lateral loading. Furthermore, the effect
of modular insertion of the detailed brain model into the M50-OS is quantified.
METHODS: Data from the Navy Biodynamics Laboratory (NBDL) human volunteer
studies, including a 15g frontal, 8g frontal, and 7g lateral impact, were
reconstructed and simulated using LS-DYNA. A five-point restraint system was used
for all simulations, and initial positions of the models were matched with
volunteer data using settling and positioning techniques. Both the frontal and
lateral simulations were run with the M50-O, M50-OS, and M50-OS+B with active
musculature for a total of nine runs. RESULTS: Normalized run times for the
various models used in this study were 8.4 min/ms for the M50-O, 0.26 min/ms for
the M50-OS, and 0.97 min/ms for the M50-OS+B, a 32- and 9-fold reduction in run
time, respectively. Corridors were reanalyzed for head and T1 kinematics from the
NBDL studies. Qualitative evaluation of head rotational accelerations and linear
resultant acceleration, as well as linear resultant T1 acceleration, showed
reasonable results between all models and the experimental data. Objective
evaluation of the results for head center of gravity (CG) accelerations was
completed via ISO TS 18571, and indicated scores of 0.673 (M50-O), 0.638 (M50
OS), and 0.656 (M50-OS+B) for the 15g frontal impact. Scores at lower g levels
yielded similar results, 0.667 (M50-O), 0.675 (M50-OS), and 0.710 (M50-OS+B) for
the 8g frontal impact. The 7g lateral simulations also compared fairly with an
average ISO score of 0.565 for the M50-O, 0.634 for the M50-OS, and 0.606 for the
M50-OS+B. The three HBMs experienced similar head and neck motion in the frontal
simulations, but the M50-O predicted significantly greater head rotation in the
lateral simulation. CONCLUSION: The greatest departure from the detailed occupant
models were noted in lateral flexion, potentially indicating the need for further
study. Precise modeling of the belt system however was limited by available data.
A sensitivity study of these parameters in the frontal condition showed that belt
slack and muscle activation have a modest effect on the ISO score. The reduction
in computation time of the M50-OS+B reduces the burden of high computational
requirements when handling detailed HBMs. Future work will focus on harmonizing
the lateral head response of the models and studying localized injury criteria
within the brain from the M50-O and M50-OS+B.
PMID- 28414546
TI - Behavioral Parent Training in Infancy: What About the Parent-Infant Relationship?
AB - Behavioral parent training (BPT) and attachment interventions have demonstrated
efficacy in improving outcomes for young children. Despite theoretical overlap in
these approaches, the literature has evolved separately, particularly with
respect to outcome measurement in BPT. We examined the impact of the Infant
Behavior Program (IBP), a brief home-based adaptation of Parent-Child Interaction
Therapy, on changes in attachment-based caregiving behaviors (sensitivity,
warmth, and intrusiveness) at postintervention and 3- and 6-month follow-ups
during a videotaped infant-led play. Sixty mother-infant dyads were randomly
assigned to receive the IBP (n = 28) or standard care (n = 30). Infants were an
average age of 13.52 months and predominately from ethnic or racial minority
backgrounds (98%). We used bivariate correlations to examine the association
between attachment-based caregiving behaviors and behaviorally based parenting do
and don't skills and structural equation modeling to examine the direct effect of
the IBP on attachment-based caregiving behaviors and the indirect effect of
behaviorally based parenting skills on the relation between intervention group
and attachment-based caregiving behaviors. Behaviorally based parenting do and
don't skills were moderately correlated with attachment-based caregiving
behaviors. Results demonstrated a direct effect of the IBP on warmth and
sensitivity at postintervention and 3- and 6-month follow-ups. The direct effect
of the IBP on warmth and sensitivity at the 3- and 6-month follow-ups was
mediated by increases in parenting do skills at postintervention. Findings
suggest that behaviorally based parenting skills targeted in BPT programs have a
broader impact on important attachment-based caregiving behaviors during the
critical developmental transition from infancy to toddlerhood.
PMID- 28414547
TI - Distribution of PERIOD-immunoreactive neurons and temporal change of the
immunoreactivity under long-day and short-day conditions in the larval brain of
the flesh fly Sarcophaga similis.
AB - The flesh fly Sarcophaga similis show a clear photoperiodic response; they
develop into adults under long days, whereas they arrest their development at the
pupal stage under short days. Although the involvement of a circadian clock in
photoperiodic time measurement is suggested in this species, the anatomical
location of the clock neurons responsible for the time measurement has been
unknown. We detected two PERIOD-immunoreactive cell clusters in the larval brain;
one cluster was located at the dorsoanterior region and the other at the medial
region. We further investigated their temporal changes in PERIOD-immunoreactivity
and compared their patterns under different photoperiods.
PMID- 28414548
TI - Assessing State Mental Contamination: Development and Preliminary Validation of
the State Mental Contamination Scale.
AB - This 2-part study described the development and preliminary validation of the
State Mental Contamination Scale (SMCS), a multi-item self-report measure of
state mental contamination. In Study 1, community adults (N = 211) in the United
States were randomly assigned to a pathogen disgust, moral disgust, or neutral
condition and then completed the SMCS. Study 1 results supported a 1-factor
structure of the SMCS items. Scores on the SMCS items evidenced good internal
consistency and strong interitem correlations. SMCS scores were significantly
greater following the 2 disgust conditions relative to the neutral condition and
a full range of SMCS scores were found in the disgust conditions. An independent
sample of community adults (N = 121) from the United States participated in Study
2 to extend Study 1 results. Study 2 results indicated that SMCS scores were
manipulated independently of trait mental contamination, more strongly related to
convergent than a discriminant measure, and shared unique variance with a
criterion measure after controlling for convergent measures. The future use of
the SMCS is discussed.
PMID- 28414549
TI - Do marine algal polyphenols have antidiabetic, antihyperlipidemic or anti
inflammatory effects in humans? A systematic review.
AB - Cardiovascular disease and type 2 diabetes are leading causes of morbidity and
mortality globally. Marine algal polyphenols have potential to reduce the risk of
these conditions, however, little is known about their impact in humans. This
systematic review investigates the antidiabetic, antihyperlipidemic and anti
inflammatory effects of marine polyphenols in humans. Scopus, Medline, PsychInfo,
Embase and Cochrane Library databases were searched in November 2016. Eligible
studies included (1) human adults, (2) marine polyphenol intervention, (3) blood
lipid, glucose, insulin or inflammatory marker outcomes, and (4) were a
randomized-controlled trial. One postprandial cross-over trial and four parallel
design trials were included involving 271 adults. Analysis across studies was
performed using Cohen's d effect sizes. Supplementation with polyphenol-rich
extracts had small-to-medium positive effects on fasting blood glucose, total
cholesterol and LDL-cholesterol; however, there is inadequate evidence as yet to
confirm if these are consistent effects. Further randomized-controlled trials
should investigate polyphenols from Ecklonia cava and other macroalgal sources,
to determine if there is a role for marine polyphenols in reducing the risk
factors of chronic disease in humans. (PROSPERO registration number
CRD42015016890).
PMID- 28414551
TI - Long Noncoding RNA MNX1-AS1 Knockdown Inhibits Cell Proliferation and Migration
in Ovarian Cancer.
AB - Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators that
govern fundamental biological processes and disease pathogenesis. LncRNA MNX1-AS1
has been reported to promote cell proliferation and invasion in gallbladder
cancer, but its biological role and regulatory mechanism in ovarian cancer are
poorly defined. In this study, it was found that higher expression of lncRNA MNX1
AS1 is closely associated with International Federation of Gynecology and
Obstetrics stage and lymphatic metastasis in ovarian cancer patients. RNA
interference (RNAi) to downregulate the expression of lncRNA MNX1-AS1 was used in
the ovarian cancer cell lines, OVCA433 and SKOV-3. CCK-8, EdU staining, and
colony formation assays was used to test the viability and proliferation ability
of these cells. Wound healing and transwell migration assays were performed to
determine the migration ability of the cells. Cell cycle progression and
apoptotic assays were carried out using flow cytometry. These in vitro loss-of
function experiments revealed that downregulation of lncRNA MNX1-AS1 suppressed
cell proliferation, colony formation, cell migration ability, induced cell cycle
arrest at the G0/G1 phase, and promoted apoptosis. Furthermore, MNX1-AS1
knockdown altered the protein expressions of CDK4, cyclin D, Bax, and Bcl-2.
These findings demonstrated for the first time that lncRNA MNX1-AS1 functions as
an oncogene in ovarian cancer and could be a potential target for this disease.
PMID- 28414550
TI - Expression of Long Noncoding RNA Urothelial Cancer Associated 1 Promotes
Cisplatin Resistance in Cervical Cancer.
AB - Cisplatin resistance is still one of the main reasons for failure of clinical
therapy for cervical cancer. But the underlying molecular mechanisms involved in
cisplatin resistance of cervical cancer have still remained unclear. Recent
studies reported that long noncoding RNAs (lncRNAs) are novel nonprotein-coding
transcripts, which might play a key role in cancer biogenesis and prognosis. One
of the lncRNAs, urothelial cancer associated 1 (UCA1), has been shown to promote
different types of cancer cell proliferation, migration, and invasion. This study
showed that overexpression of UCA1 confers cisplatin resistance by promoting
cancer cell proliferation and inhibiting apoptosis. In addition, knockdown of
UCA1 remarkably decreased cisplatin resistance in cervical cancer cells.
Moreover, results also indicated that UCA1 was involved in signaling pathways
modulating cell apoptosis and proliferation. UCA1 suppressed apoptosis by
downregulating caspase 3 and upregulating CDK2, whereas enhanced cell
proliferation by increased level of survivin and decreased level of p21. This
study reports for the first time that UCA1 might play an important role in the
cisplatin resistance in cervical cancer, and also explain partially how UCA1
promotes cisplatin resistance in cancer cells. These results provide evidence to
support that UCA1 can be used as a potential target for a novel therapeutic
strategy for cervical cancer.
PMID- 28414552
TI - AAV Is Now a Medicine: We Had Better Get This Right.
PMID- 28414553
TI - GD-RDA: A New Regularized Discriminant Analysis for High-Dimensional Data.
AB - High-throughput techniques bring novel tools and also statistical challenges to
genomic research. Identification of which type of diseases a new patient belongs
to has been recognized as an important problem. For high-dimensional small sample
size data, the classical discriminant methods suffer from the singularity problem
and are, therefore, no longer applicable in practice. In this article, we propose
a geometric diagonalization method for the regularized discriminant analysis. We
then consider a bias correction to further improve the proposed method.
Simulation studies show that the proposed method performs better than, or at
least as well as, the existing methods in a wide range of settings. A microarray
dataset and an RNA-seq dataset are also analyzed and they demonstrate the
superiority of the proposed method over the existing competitors, especially when
the number of samples is small or the number of genes is large. Finally, we have
developed an R package called "GDRDA" which is available upon request.
PMID- 28414554
TI - Antitumor activity of the pachymic acid in nasopharyngeal carcinoma cells.
AB - OBJECTIVE: To investigate the antitumour efficacy of pachymic acid (PA), which is
a fungal extract component, on nasopharyngeal carcinoma (NPC) cells CNE-1, CNE-2.
METHODS: We have chosen NPC cell line CNE-2 for the study, and the cells were
treated with PA before the detection. CCK-8 assay was used to detect the
proliferative ability, and Annexin V-PI double staining was used for the
detection of apoptosis rate; and the nucleus damage was detected by transmission
electron microscope, the protein expression of the DNA damage pathway were
detected by Western blot. RESULTS: PA can significantly inhibited proliferation
of CNE-1, CNE-2 cells. The proportion of apoptotic cells of all cell lines
gradually increased in a dose-dependent manner induced by PA, P < 0.05.
Meanwhile, the nucleus could be caused morphological changes and the expression
of DNA damage-related proteins was upregulated by PA in CNE-2. CONCLUSIONS: PA
can significantly inhibit cell proliferation and increase the apoptosis rates and
may induce the apoptosis of the human NPC cells.
PMID- 28414555
TI - Making the Right Thing Easier to Do: Standardized Integration of Oncology and
Palliative Care.
PMID- 28414556
TI - Dynamic Equilibrium.
PMID- 28414557
TI - Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica
nanoparticles as a targeted drug delivery system for bladder cancer therapy.
AB - We reported a simple polydopamine (PDA)-based surface modification method to
prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and
peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the
therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in
terms of size, size distribution, zeta potential, transmission electron
microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading
content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA
PEP had similar release kinetic profiles of DOX. The PDA coating well controlled
DOX release and was highly sensitive to pH value. Confocal laser scanning
microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human
bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest
cellular uptake efficiency due to ligand-receptor recognition. The antitumor
effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and
by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX
loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded
MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT
1376 cells, can be used as a potential targeted drug delivery system for bladder
cancer therapy.
PMID- 28414558
TI - Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1
Responses in Behcet's Disease.
AB - OBJECTIVES: Interleukin-17 (IL-17) has been associated with the pathogenesis of
various autoimmune/inflammatory diseases. The aim of this study was to
investigate the expression of Th17-related immunity in an innate immunity
dominated vasculitis, namely Behcet's disease (BD). METHODS: Peripheral blood
mononuclear cells from 37 patients (age: 38.5 +/- 9.8 years) with BD, and 25
healthy controls (HC) (age: 39.1 +/- 9.3 years), were cultured in Th17-inducing
conditions (IL-6, Phytohemagglutinin (PHA), IL-1beta, and IL-23) for 6 days.
Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon
gamma (IFN-gamma), and IL-17 antibodies to determine the intracellular cytokine
secretion by flow cytometry. RESULTS: IL-17 expression by CD8+ and gammadelta+ T
cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No
differences were observed between the groups in the IL-17 production by B cells.
Under Th17-inducing conditions, production of IFN-gamma by CD4+, CD8+, and
gammadelta+ T cells was also higher in BD compared to HC (p < 0.05 in all).
CONCLUSION: Our results suggest that under Th17-stimulating conditions, T cells
express both IL-17 and IFN-gamma in BD. More prominent IL-17 and IFN-gamma
production by all lymphocyte subsets in BD might be associated with the increased
innate responses, early tissue neutrophil infiltrations and late adaptive
immunity in BD.
PMID- 28414559
TI - Evaluating the Cost and Utility of Mandating Schools to Stock Epinephrine Auto
injectors.
AB - BACKGROUND: The Michigan Legislature mandated that all public schools stock
epinephrine auto-injectors (EAIs). A minimal amount is known regarding the
incremental value of EAIs in schools. Our primary objective was to describe the
frequency of administration of epinephrine for EMS patients with acute allergic
reactions in public schools. Our secondary objective was to estimate the cost of
mandating public schools to stock EAIs. METHODS: We performed a retrospective
cohort study of EMS cases with an impression of allergic reaction and who
received epinephrine recorded in the 2014 Michigan EMS Information System (MI
EMSIS). We abstracted patient demographics, incident location by address to
identify public schools, source of epinephrine given, and suspected allergen if
known. We calculated advanced life support (ALS) response times to assess
temporal impact of school EAIs in communities with ALS systems. We estimated the
unsubsidized annual procurement cost of this mandate for Michigan public schools
(N = 4,039), using range of costs for the required 2 EAIs (adult and pediatric)
as estimated by the legislature ($140/each) and recently reported costs for
commercial sources ($1,200). Training costs were not included. Descriptive
statistics are reported. RESULTS: During this period, there were 1,550,009 EMS
cases in the state with 631 receiving non-cardiac arrest epinephrine for presumed
anaphylaxis, of which 23 cases were in public schools. Reported allergens were
most often food 12 (51.2%), insect stings 4(22.2%) or unknown 7(30.4%). Among
these patients, the source for epinephrine used was from the student, 7 (30.4%),
EMS 7 (30.4%), school 7(30.4%), and unknown 2(8.7%). A majority (21, 91.3%) of
the public school cases occurred in communities with ALS systems and ALS response
was relatively rapid (median response 6 minutes, 90 percentile, 13 minutes). The
unsubsidized annual cost of Michigan public schools to stock EAIs ranges from
$565,460 to $4,846,800. CONCLUSION: In this study, few public school patients
received epinephrine for anaphylaxis and the vast majority occurred in
communities with rapid ALS response. The direct annual supply cost of the school
EAI mandate is substantial.
PMID- 28414560
TI - Aloe arborescens Polysaccharides: In Vitro Immunomodulation and Potential
Cytotoxic Activity.
AB - Different polysaccharides were isolated from the leaves of Aloe arborescens using
the gradient power of hydrogen followed by antitumor and immunomodulatory assay.
The total polysaccharide content of different fractions, water-soluble
polysaccharide (WAP), acid-soluble polysaccharide (ACP), and alkaline-soluble
polysaccharide (ALP), was estimated using a phenol-sulfuric acid
spectrophotometric method. WAP possessed a higher content of mannose and glucose
than either ACP or ALP. In vitro antitumor activity was investigated in three
different cancer cell lines, and in vitro immunomodulatory potential was assessed
through phagocytosis and lymphocyte transformation assay. The results showed that
WAP and ALP exhibited the most significant cytotoxicity against HepG2 human liver
cancer cells, with IC50 values of 26.14 and 21.46 MUg/mL, respectively. In
contrast, ALP was able to enhance lymphocyte transformation, whereas WAP had the
most potent phagocytic activity. Molecular weight, total sugar and uronic acid
content, Fourier transform-infrared analysis, and linkage type of bioactive
polysaccharides were investigated. These findings revealed that the potential
antitumor activity of the natural agents WAP and ALP was through an
immunomodulation mechanism, which verifies the use of the plant as adjuvant
supplement for cancer patients suffering immunosuppression during chemotherapy.
PMID- 28414561
TI - Interferon Alpha for the Treatment of Cystoid Macular Edema Associated with
Presumed Ocular Tuberculosis.
AB - PURPOSE: To report the efficacy and safety of interferon (IFN) alpha-2a in
patients with cystoid macular edema (CME) associated with presumed ocular
tuberculosis (TB). METHODS: We reviewed the clinical records of 5 patients with
presumed ocular TB who had been treated with IFN alpha-2a for recurrent CME
during or after completion of anti-tubercular therapy. IFN alpha-2a was
administered at an initial dose of 3 million IU per day and then tapered after
the initial response. Treatment efficacy was assessed by central macular
thickness (CMT) measurement using spectral-domain optical coherence tomography
and visual acuity. RESULTS: Three patients were men, and 2 were women. Patients
were aged between 38 and 66 years. Mean CMT was 483 +/- 178.6 MUm at baseline,
302.3 +/- 56 MUm at 1 week, 312.3 +/- 49.5 MUm at 1 month, and 286.2 +/- 31.9 MUm
at 3 months. Mean LogMAR visual acuity was 0.6 +/- 0.4 at baseline, 0.4 +/- 0.3
MUm at 1 week, 0.3 +/- 0.3 at 1 month, and 0.3 +/- 0.3 at 3 months. The treatment
was interrupted for 10 days because of neutropenia after 2 weeks in 1 patient and
discontinued in another after 10 days because of intolerance. Total treatment
duration was 3-24 months in the remaining 4 patients. CONCLUSION: The present
small case series suggests that IFN alpha-2a may be an effective and safe
therapeutic option for CME that is associated with presumed ocular TB.
PMID- 28414562
TI - A Review of Cochrane Systematic Reviews of Interventions Relevant to Orthoptic
Practice.
AB - AIM: To present an overview of the range of systematic reviews on intervention
trials pertinent to orthoptic practice, produced by the Cochrane Eyes and Vision
group (CEV). METHODS: We searched the 2016 Cochrane Library database (31.03.2016)
to identify completed reviews and protocols of direct relevance to orthoptic
practice. These reviews are currently completed and published, available on
www.thecochranelibrary.com (free to UK health employees) or via the CEV website
(http://eyes.cochrane.org/) . RESULTS: We found 27 completed CEV reviews across
the topics of strabismus, amblyopia, refractive errors, and low vision. Seven
completed CEV protocols addressed topics of strabismus, amblyopia, refractive
errors, low vision, and screening. We found 3 completed Cochrane Stroke reviews
addressing visual field loss, eye movement impairment, and age-related vision
loss. CONCLUSIONS: The systematic review process presents an important
opportunity for any clinician to contribute to the establishment of reliable,
evidence-based orthoptic practice. Each review has an abstract and plain language
summary that many non-clinicians find useful, followed by a full copy of the
review (background, objectives, methods, results, discussion) with a conclusion
section that is divided into implications for practice and implications for
research. The current reviews provide patients/parents/carers with information
about various different conditions and treatment options, but also provide
clinicians with a summary of the available evidence on interventions, to use as a
guide for both clinical practice and future research planning. The reviews
identified in this overview highlight the evidence available for effective
interventions for strabismus, amblyopia, refractive errors, and low vision or
stroke rehabilitation as well as the gaps in the evidence base. Thus, a demand
exists for future robust, randomized, controlled trials of such interventions of
importance in orthoptic practice.
PMID- 28414563
TI - Leveraging Stem Cell Homing for Therapeutic Regeneration.
AB - Resident stem cell pools in many tissues/organs are responsible not only for
tissue maintenance during physiologic turnover but also for the process of wound
repair following injury. With inspiration from stem cell trafficking within the
body under physiologic and pathologic conditions, recent advances have been made
toward inducing stem cell mobilization and directing patients' own cells to sites
of interest for treating a broad spectrum of diseases. An evolving body of work
corroborates that delivering guidance cues can mobilize stem cells from the bone
marrow and drive these cells toward a specific region. In addition, the
transplantation of cell-friendly biomaterials incorporating certain biomolecules
has led to the regeneration of lost/damaged tissue without the need for
delivering cellular materials manipulated ex vivo. Recently, cell homing has
resulted in remarkable biological discoveries in the laboratory as well as great
curative successes in preclinical scenarios. Here, we review the biological
evidence underlying in vivo cell mobilization and homing with the aim of
leveraging endogenous reparative cells for therapeutic applications. Considering
both the promise and the obstacles of this approach, we discuss how matrix
components of the in vivo milieu can be modified to promote the native
regenerative process and inspire future tissue-engineering design.
PMID- 28414564
TI - Tivantinib for the treatment of hepatocellular carcinoma.
AB - INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the leading causes of
cancer-related death worldwide with a poor prognosis due to late diagnosis in the
majority of cases. Physicians are frequently confronted with patients who are not
eligible for curative or locoregional treatments any more. In this scenario, the
multi-tyrosine kinase inhibitor sorafenib remains the only systemic first-line
treatment option providing modest survival benefit compared to placebo with
significant but for most patients acceptable adverse effects. Areas covered:
Tivantinib was the first antiproliferative agent to be been applied in a phase
III trial based on receptor overexpression analyses after disease progression on
sorafenib. While phase I and II trials with tivantinib in second line showed
encouraging results, a recent press release announced that the METIV-HCC phase
III study of tivantinib in HCC did not meet its primary endpoint of improving
overall survival. Expert commentary: Evidence for antiangiogenetic therapy
inducing tumor hypoxia leading to overexpression of proliferative genes,
including cMET, underlines the potential of tivantinib as second-line treatment.
However, as the mechanism of action of tivantinib through cMET inhibition has
recently been questioned by several groups, identification of alternative
proliferative markers or targets is mandatory.
PMID- 28414565
TI - New Regenerative Vascular Grafts for Hemodialysis Access: Evaluation of a
Preclinical Animal Model.
AB - The purpose of this study was to evaluate a suitable animal model for the in vivo
evaluation of patency and vascular tissue regeneration in small intestinal
submucosa (SIS) vascular grafts for hemodialysis access. First, a 4-mm U-shaped
SIS vascular graft was implanted between the internal carotid artery (CA) and the
external jugular vein (JV) in five sheep and six swine. The U-shape grafts
remained functional for 53 +/- 4 days in sheep and 32 +/- 2 days in swine. The
sheep model presented exaggerated inflammation, so the swine model was selected
for the in vivo study. Based on these initial results, a 4-mm C-shape SIS
vascular graft with SIS circumferential reinforcement was developed to
mechanically improve the vascular graft and manage complications identified
during surgery in both sheep and swine. The C-shape vascular graft was implanted
in a swine model (n = 3) between the CA and JV. GORE-TEX(r) vascular grafts were
used as controls in the contralateral side of the neck. C-shape grafts remained
patent for 47 +/- 4 days, whereas the GORE-TEX(r) grafts were patent for 30 +/-
15 days. The C-shape vascular graft was easier to handle during surgery, and its
circumferential reinforcement improved in vivo patency, avoiding kinks in the
graft after implantation. Histological results showed neovascularization and some
regeneration with the alignment of endothelial cells in the vascular wall of the
grafts. The model developed may be helpful in other research involving in vivo
studies of vascular grafts for hemodialysis access.
PMID- 28414566
TI - The Changed Proportion of CD45RA+/CD45RO+ T Cells in Chronic Hepatitis C Patients
During Pegylated Interferon-alpha with Ribavirin Therapy.
AB - Infection with the hepatitis C virus (HCV) may progress toward chronic hepatitis,
liver cirrhosis, and liver cancer. A therapy for patients with chronic HCV
infection is the combination of pegylated interferon-alpha with ribavirin, which
increases the rate of sustained virological response (SVR) to 56%. However, a
practical biomarker to predict SVR is lacking. T cells expressing the CD45RA
isoform are considered naive, and antigenic stimulation converts them to CD45RO+.
CD45RO+ T cells exhibit immediate response and high lymphokine production,
leading to the maintenance and upregulation of immune reactions. The aim of this
study is to clarify the proportions of CD45RA+ and CD45RO+ T cells associated
with rapid virological response and SVR. We collected blood samples from 32 HCV
patients receiving the combined treatment. The samples were collected before,
during 4th, 12th, and 24th therapy weeks, and 4th week posttherapy, and their T
cell populations were analyzed using flow cytometry. Twenty-nine patients (90.6%)
achieved SVR. There were significant declines in proportions of CD45RA+ cells
during 4th, 12th, and 24th therapy weeks, and significant increases in
proportions of CD45RO+ cells during 24th therapy week and 4th week posttherapy (P
< 0.05). Patients undergoing hepatitis C therapy exhibited lowered CD45RA+ cell
proportions and increased CD45RO+ cell proportions. This effect may be important
in a patient's response to pegylated interferon-alpha with ribavirin therapy.
PMID- 28414567
TI - Disease burden of community acquired pneumonia among children under 5 y old in
China: A population based survey.
AB - BACKGROUND: To obtain the baseline data on the incidence and cost of community
acquired pneumonia among under-5 children for future studies, and provide
evidence for shaping China's strategies regarding pneumococcal conjugate vaccine
(PCV). METHODS: Three townships from Heilongjiang, Hebei and Gansu Province and
one community in Shanghai were selected as study areas. A questionnaire survey
was conducted to collect data on incidence and cost of pneumonia among children
under 5 y old in 2012. RESULTS: The overall incidence of clinically diagnosed
pneumonia in children under 5 y old was 2.55%. The incidence in urban area was
7.97%, higher than that in rural areas (1.68%). However, no difference was found
in the incidences of chest X-ray confirmed pneumonia between urban and rural
areas (1.67% vs 1.23%). X-ray confirmed cases in rural and urban areas
respectively accounted for 73.45% and 20.93% of all clinically diagnosed
pneumonia. The hospitalization rate of all cases was 1.40%. Incidence and
hospitalization rate of pneumonia decreased with age, with the highest rates
found among children younger than one year and the lowest among children aged 4
(incidence: 4.25% vs 0.83%; hospitalization: 2.75% vs 0.36%). The incidence was
slightly higher among boys (2.92% vs 2.08%). The total cost due to pneumonia for
the participants was 1138 733 CNY. The average cost and median cost was 5722 CNY
and 3540 CNY separately. Multivariate analysis showed that the only factor
related to higher cost was hospitalization. CONCLUSIONS: The disease burden was
high for children under 5 y old, especially the infant. PCV has not been widely
used among children, and thus further health economics evaluation on introducing
PCV into National Immunization Program should be conducted.
PMID- 28414568
TI - Moving Beyond Traditional Cardiovascular Risk Factors Toward Gendered Horizon.
PMID- 28414569
TI - Elevated Levels of Plasma Mitochondrial DNA Are Associated with Clinical Outcome
in Intra-Abdominal Infections Caused by Severe Trauma.
AB - BACKGROUND: The purpose of our study was to determine prospectively relationships
between plasma mitochondrial deoxyribonucleic acid (mtDNA) concentration and
clinical outcome in patients with intra-abdominal infections (IAIs) induced by
severe abdominal trauma. PATIENTS AND METHODS: The DNA was isolated from serum
samples taken from patients with IAIs at hospital days zero, one, and two. Plasma
mtDNA concentration was assessed by real-time polymerase chain reaction (PCR).
The study population's clinical and laboratory data were analyzed. RESULTS: The
mtDNA damage-associated molecular patterns were expressed as a PCR threshold
cycle number using four selected sequences. The patients with IAIs had
significant higher plasma mtDNA than healthy control subjects. Patients with IAIs
with sepsis apparently had elevated mtDNA levels compared with non-septic
patients with IAIs (30.9 +/- 2.0 vs. 28.7 +/- 2.4; 33.3 +/- 2.6 vs. 28.9 +/- 2.4;
32.9 +/- 1.6 vs. 31.2 +/- 2.2; 33.1 +/- 3.6 vs. 28.1 +/- 2.2, respectively).
Patients with IAIs in whom multiple organ dysfunction syndrome (MODS) developed
also had increased mtDNA concentration compared with those who did not (31.0 +/-
1.8 vs. 27.9 +/- 1.8; 32.9 +/- 2.4 vs. 27.8 +/- 1.7; 32.9 +/- 1.5 vs. 29.8 +/-
1.7; 32.0 +/- 3.8 vs. 27.1 +/- 2.1, respectively). Baseline mtDNA concentration
had high effectiveness in predicting death for patients with IAIs who had severe
trauma using receiver operating characteristic analysis. Furthermore, serum mtDNA
levels on admission correlated with the lactate concentration, but no significant
correlations were found between mtDNA levels and levels of white blood cells, C
reactive protein, and procalcitonin. CONCLUSIONS: Plasma mtDNA was associated
with the occurrence of sepsis, MODS, and death in patients with IAIs caused by
severe abdominal trauma.
PMID- 28414570
TI - Perceived Stress in Online Prostate Cancer Community Participants: Examining
Relationships with Stigmatization, Social Support Network Preference, and Social
Support Seeking.
AB - Men with prostate cancer often need social support to help them cope with illness
related physiological and psychosocial challenges. Whether those needs are met
depends on receiving support optimally matched to their needs. This study
examined relationships between perceived stress, prostate cancer-related stigma,
weak-tie support preference, and online community use for social support in a
survey of online prostate cancer community participants (n = 149). Findings
revealed a positive relationship between stigma and perceived stress. This
relationship, however, was moderated by weak-tie support preference and online
community use for social support. Specifically, stigma was positively related to
perceived stress when weak-tie support was preferred. Analyses also showed a
positive relationship between stigma and perceived stress in those who used their
online community for advice or emotional support. Health communication scholars
should work collaboratively with diagnosed men, clinicians, and online community
administrators to develop online interventions that optimally match social
support needs.
PMID- 28414571
TI - The Novel Technique of Transabdominal Preperitoneal Hernioplasty Herniorrhaphy
for Direct Inguinal Hernia: Suture Repair of Hernia Defect Wall.
AB - BACKGROUND: Conventional laparoscopic surgeries of direct inguinal hernia include
two methods, transabdominal preperitoneal hernioplasty (TAPP) and totally
extraperitoneal hernioplasty. Both methods are performed using synthetic mesh
without suturing the hernia defect and require extensive mesh coverage for not
only Hesselbach's triangle but also indirect ring. For minimally invasive
operation, suture of direct hernia defect was devised and performed. The purpose
of this study is to evaluate the efficacy of defect wall suture of laparoscopic
herniorrhaphy for direct inguinal hernia patients. METHODS: We evaluated 210
direct inguinal hernia patients who received TAPP in Damsoyu Hospital, Seoul,
Republic of Korea from September 2012 to December 2015. The patients were
categorized into two groups according to TAPP techniques; cTAPP group had
conventional TAPP without defect wall suture, and rTAPP group had defect wall
suture TAPP. There were 99 patients in a cTAPP group and 111 patients in rTAPP
group. RESULTS: Operation time and postoperative hospital stay showed no
difference between two groups. The postoperative pain score within the first week
was significantly lower in rTAPP group than in cTAPP group (P < .001). The mean
timing of a return to normal activities for rTAPP group was 3.8 days, which was
shorter than 4.6 days of cTAPP group (P < .001). There was no difference in
complication and recurrence rates between two groups. CONCLUSIONS: Defect wall
suture for direct inguinal hernia had shorter operation time, faster recovery
time, reduced pain, and an acceptable rate of recurrence and complication. This
TAPP surgery with hernia defect wall suture that requires smaller dissection area
is an effective method for treating direct inguinal hernia.
PMID- 28414572
TI - Molecular Characterization of Fluoroquinolone-Resistant Haemophilus
parainfluenzae Clinical Isolates in Spain.
AB - OBJECTIVE: The objective was to characterize a group of clinical isolates of
fluoroquinolone-resistant Haemophilus parainfluenzae collected in Northern Spain
(March-December 2014). METHODS: Twelve clinical isolates of H. parainfluenzae
were studied by performing antimicrobial susceptibility testing and PCR
amplification and nucleotide sequencing of the QRDR (quinolone resistance
determining region) of gyrA, parC, gyrB, and parE genes. Screening for plasmid
mediated quinolone resistance (PMQR) was also studied. Pulsed-field gel
electrophoresis (PFGE) was used for molecular typing. RESULTS: Antimicrobial
susceptibility testing showed that all the isolates were resistant to the
fluoroquinolones tested (ciprofloxacin, levofloxacin, norfloxacin, and
moxifloxacin). Analysis of the QRDR demonstrated that all the isolates presented
mutations in gyrA and parC. A Glu88Lys substitution in ParC is reported for the
first time in H. parainfluenzae. No PMQR gene was detected. PFGE results showed
that isolates were not clonally related. CONCLUSION: Multiple H. parainfluenzae
fluoroquinolone-resistant isolates grouped in the same area in a short period of
time showed diverse substitutions in QRDR of gyrA/parC and were not clonally
related, indicating individual emergence. In addition, we described the first
report of Glu88Lys substitution in ParC.
PMID- 28414573
TI - Phosphatidylserine Translocation after Radiosurgery in an Animal Model of
Arteriovenous Malformation.
AB - Phosphatidylserine (PS) is asymmetrically distributed across the plasma membrane,
located predominantly on the inner leaflet in healthy cells. Translocation of PS
to the outer leaflet makes it available as a target for biological therapies. We
examined PS translocation after radiosurgery in an animal model of brain
arteriovenous malformation (AVM). An arteriovenous fistula was created by end-to
side anastomosis of the left external jugular vein to the common carotid artery
in 6-week-old, male Sprague Dawley rats. Six weeks after AVM creation, 15 rats
underwent Gamma Knife stereotactic radiosurgery receiving a single 15 Gy dose to
the margin of the fistula; 15 rats received sham treatment. Externalization of PS
was examined by intravenous injection of a PS-specific near-infrared probe, PSVue
794, and in vivo fluorescence optical imaging at 1, 7, 21, 42, 63 and 84 days
postirradiation. Fluorescent signaling indicative of PS translocation to the
luminal cell surface accumulated in the AVM region, in both irradiated and
nonirradiated animals, at all time points. Fluorescence was localized
specifically to the AVM region and was not present in any other anatomical sites.
Translocated PS increased over time in irradiated rats (P < 0.001) but not in
sham-irradiated rats and this difference reached statistical significance at day
84 (P < 0.05). In summary, vessels within the mature rat AVM demonstrate elevated
PS externalization compared to normal vessels. A single dose of ionizing
radiation can increase PS externalization in a time-dependent manner. Strict
localization of PS externalization within the AVM region suggests that
stereotactic radiosurgery can serve as an effective priming agent and PS may be a
suitable candidate for vascular-targeting approaches to AVM treatment.
PMID- 28414574
TI - Examining Acceptability of Self-Collection for Human Papillomavirus Testing Among
Women and Healthcare Providers with a Broader Lens.
PMID- 28414575
TI - Prevalence of Violence Toward Community Nurses: A Questionnaire Survey.
AB - Violence toward nursing staff occurs frequently, particularly in intensive care
units and closed or intensive psychiatric facilities, which have been studied
previously. However, violence toward community nurses has not been investigated.
The purpose of this study was to explore the frequency of violence toward
community nurses in Slovenia. More than 56% of study respondents were verbally
abused by their patients during the past year. More than 42% of all cases of
horizontal violence were directed at community nurses.
PMID- 28414576
TI - HCBS Spending and Nursing Home Admissions for 1915(c) Waiver Enrollees.
AB - Medicaid waiver programs for home- and community-based services (HCBS) have grown
rapidly and serve a population at high risk for nursing home (NH) admission. This
study utilized the Medicaid Analytic Extract Personal Summary File and the NH
Minimum Data Set and tested whether higher levels of per-beneficiary HCBS
spending were associated with (1) lower risk of long-term (90+ days) NH admission
and (2) higher functional/cognitive impairment at admission for new enrollees in
1915(c) aged or aged and disabled waiver programs. Waiver enrollees in states and
counties with higher HCBS spending were found to have lower risk of long-term NH
admission and greater functional impairment at NH admission compared to waiver
enrollees in states and counties with lower spending. This indicates that higher
per-enrollee HCBS spending may enable waiver enrollees to remain in the community
until their functional impairment becomes more severe.
PMID- 28414577
TI - Serum Toll-Like Receptor-2, Toll-Like Receptor-4 Levels in Patients with HBeAg
Negative Chronic Viral Hepatitis B.
AB - Toll-like receptors (TLRs) may play an important role in hepatitis-B
pathogenesis. However, serum TLR-2 and TLR-4 levels and their association with
serum liver enzymes, hepatitis B virus (HBV) DNA, quantitative HBsAg levels, and
liver biopsy findings, are unknown. A total of naive 40 HBeAg (-) chronic
hepatitis B (CHB) patients and 20 healthy control subjects were recruited in this
study. Liver tests, HBV DNA, serum TLR-2 and TLR-4, and quantitative HBsAg levels
were evaluated among all groups. The relationship among TLR-2, TLR-4,
quantitative HBsAg levels and liver tests, and liver histological findings were
investigated with correlation analysis. Serum TLR-2 and TLR-4 levels in HBeAg (-)
CHB patients were higher than in the control group. There was a positive
correlation between serum TLR-2, TLR-4, and HBV DNA and ALT levels. We have
further demonstrated that serum TLR-2 levels are correlated with AST and
quantitative HBsAg levels. However, TLRs levels were not linked to the liver
biopsy findings. TLR can have an important role in hepatitis B pathogenesis.
Liver injury in CHB may cause elevated TLR-2 and TLR-4 levels.
PMID- 28414578
TI - The Impact of In-Home Services Utilization on the Institutionalization of Older
People in Korea.
AB - As a result of aging populations, institutionalization of older people is
creating an increasing financial burden in many countries. The purpose of the
present study was to explore the impact of in-home service utilization on
institutionalization. The subjects were newly certified as eligible for long-term
care insurance between January and February 2009 in Korea. The follow-up period
was 40 months, to April 2012. We used logistic regression models to identify
factors influencing the transition to institutional service, adjusting for
gender, age, living status, income level, activities of daily living, and chronic
disease. The institutionalization rate was estimated to be 17.3% over 40 months.
The interval from transitional living to institutionalization was 36 +/- 8
months. Risk factors of transition to institutional services are being female,
having advanced age, living with friends or cousins, getting dementia, and not
using in-home services. We determined that institutionalization is mitigated by
use of in-home services. Therefore, supplying appropriate in-home services to
current nonusers would help to greatly reduce the rate of institutionalization of
older people.
PMID- 28414579
TI - Housing First for Adults with Problematic Substance Use.
AB - OBJECTIVES: This study explores the two-year housing- and non-housing-related
outcomes for adults who are homeless with problematic substance use who received
scattered-site housing and intensive case management services from a Housing
First program in Ottawa, Canada, in comparison with a group of adults who are
homeless with problematic substance use who had access to standard care in the
community. METHODS: Housing First clients (n = 89) and members of a comparison
group (n = 89) completed structured interviews at baseline and were followed for
two years. RESULTS: Housing First clients moved into housing more quickly,
reported a greater proportion of time housed, were more likely to spend the final
six months housed, and had longer housing tenure at 24 months. There was a group
by time interaction on problematic alcohol use with more rapid improvement for
the comparison group; however, both groups improved over time. The comparison
group had a greater decrease on problematic drug use by 24 months. There was no
change in physical health and only the comparison group had improvements in
mental health by 24 months. The groups had similar improvement on community
functioning by 24 months. The comparison group had a greater increase in total
quality of life. More specifically, the comparison group had an increase in the
family relations-related quality of life, whereas the clients did not. There was
a significant interaction for safety-related quality of life, but both groups
experienced improvements over time and had comparable levels of satisfaction with
safety at each time point. The Housing First clients reported higher levels of
satisfaction with living conditions than the comparison group at baseline and 12
months, but not at 24 months. There was significant improvement over time and no
main effect of group for finances, leisure, and social relations. CONCLUSIONS:
Adults who are homeless with problematic substance use can successfully be housed
using a Housing First approach. However, further targeted services might be
required to address other areas of functioning, such as health, substance use,
and quality of life.
PMID- 28414580
TI - Identifying Personal Risk Factors for Falls in the Workplace.
AB - Falls can occur in any occupational setting. Occupational health professionals
may focus on creating a safe work environment and training programs to prevent
falls. However, an important aspect of safety management is identifying at-risk
employees. The purpose of this article is to identify personal risk factors and
offer interventions to prevent falls in the workplace.
PMID- 28414581
TI - Posttraumatic growth after cancer: The role of perceived threat and cognitive
processing.
AB - This study examines the relation between perceived cognitive and physical threat
after a cancer diagnosis and posttraumatic growth (PTG). In total, 169 breast,
prostate, and colorectal cancer survivors completed questionnaires. Hierarchical
regression models found after controlling for demographic and medical variables,
depression, anxiety, and perceived threat account for 41.8% of the variance of
positive cognitive processing, and these variables along with positive cognitive
processing accounted for 42.7% of the variance of PTG. Positive cognitive
processing mediated the pathways between perceived physical threat and PTG.
Cognitive processing appears to play a key role in the emergence of PTG following
cancer. By exploring survivors' cognitions and perceived threat, psychosocial
providers may help cancer survivors cultivate PTG.
PMID- 28414582
TI - Educating the next generation of family caregivers through the use of dynamic
case studies.
AB - Between 2008 and 2016, students in an Introduction to Gerontology course were
required to complete a dynamic case study project simulating caregiving
arrangement decision making. Students were divided into groups representing
typical multigenerational families and were required to determine how to develop
caregiving arrangements to respond to an older family member' s changing levels
of need. The assignment concluded with students writing a final paper summarizing
what they learned. This study examined the themes emerging from student group
case study papers to gain an understanding of the challenges students face in
understanding the dynamics of making family-based caregiving decisions. This is
of particular importance as many students were seeking careers in human services
and would be assisting clients in such decision-making processes, as well as
involvement in decision making for their own family members. Themes that emerged
from group papers and the implications related to gerontology education and
policy are discussed.
PMID- 28414584
TI - Screening Commercial Vehicle Drivers for Obstructive Sleep Apnea: Tools,
Barriers, and Recommendations.
AB - Obstructive sleep apnea (OSA) is a disorder characterized by a cessation of
breathing during sleep, leading to poor sleep patterns and daytime somnolence.
Daytime somnolence is of particular concern for commercial vehicle drivers, whose
crash risk increases 50% with untreated OSA. The process of diagnosing and
treating OSA in commercial drivers begins with effective and consistent
screening. Therefore, the researchers screened drivers with both the STOP-Bang
Questionnaire and the Obstructive Sleep Apnea Evaluation Worksheet (OSAEW) and
compared the two tools. Drivers screening positive on the STOP-Bang
Questionnaire, OSAEW, and both questionnaires were 28%, 23%, and 13%,
respectively. Sleep study referrals were made for 50 drivers; 12 drivers were
scheduled for sleep tests within 3 months. Health care provider referral rates
for drivers screening at high risk (37%) and commercial driver monitoring rates
(24%) were both low. Recommendations to improve OSA screening and testing
practices include Federal Motor Carrier Safety Administration-mandated screening
and referral guidelines, employee-facilitated sleep testing, and OSA awareness
campaigns.
PMID- 28414583
TI - Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking
Cessation Attempt with Varenicline and Behavioral Therapy.
AB - OBJECTIVE: Smoking prevalence rates are elevated in individuals with
schizophrenia spectrum disorders (SSD) compared with the general population, with
attendant disproportionate smoking-related morbidity and mortality.
Pharmacotherapies that improve abstinence rates in this population are
underutilized, partly due to concerns about neuropsychiatric safety, particularly
for those with comorbid depression or prior suicide attempt. Prospective
assessment of the psychiatric safety profile of varenicline in those with SSD is
needed. METHODS: Adult smokers with SSD entered a 12-week trial of varenicline
and behavioral therapy for smoking cessation. Depressive symptoms were assessed
with the Calgary Depression Scale for Schizophrenia (CDSS) at baseline and weekly
thereafter. Participants with baseline and one or more postbaseline CDSS
assessments, n = 179, were included in a secondary analysis of change in
depressive symptoms with varenicline treatment, adjusting for abstinence status
and baseline depressive symptoms. RESULTS: Twenty-seven percent of participants
had a CDSS score at baseline consistent with current major depressive disorder,
and more than half had a prior suicide attempt. Forty-one percent (74/179)
achieved two or more weeks of continuous abstinence at the end of treatment. CDSS
scores declined 31% during the 12-week treatment period. Controlling for baseline
CDSS scores, depressive symptoms declined over time in those who completed the
trial, independent of abstinence status, and either declined or remained
unchanged in those with major depressive disorder or prior suicide attempt or who
were taking antidepressant medication. Those who did not complete the trial had
no change in depressive symptoms. DISCUSSION: Depressive symptoms declined in
adults with schizophrenia during 12 weeks of varenicline treatment and cognitive
behavioral therapy, independent of tobacco abstinence. Smokers with SSD who have
significant depressive symptoms may be successful in smoking cessation attempts
with pharmacotherapeutic aids such as varenicline while maintaining stable
psychiatric symptoms. This is a secondary analysis of data collected as part of a
clinical trial registered as NCT00621777, at www.clinicaltrials.gov .
PMID- 28414585
TI - Race, Language, or Length of Residency? Explaining Unequal Uptake of Government
Pensions in Canada.
AB - Canada's old age security (OAS), a flat-benefit public pension, is
internationally lauded as an accessible and effective safety net for seniors.
This paper explores discrepancies in OAS uptake using Canadian Census data from
1996 to 2011. Our findings demonstrate disparities in OAS uptake based on
immigration status, language proficiency, and visible minority status, disputing
claims of "universal" OAS provision. Multivariate analyses confirm a strong
"immigrant effect," with being in Canada for 20 years or less leading to lower
rates of OAS utilization. They also confirm that those not proficient in Canada's
official languages are less likely to receive OAS benefits. However, the
influence of racialized minority status is found to be spurious; after
controlling for immigration status and official language proficiency, many
racialized minority senior groups have higher odds of receiving OAS than White
Canadians. We conclude with a brief discussion of the tradeoffs involved in
considering a potential removal of OAS eligibility barriers for immigrants in
Canada.
PMID- 28414587
TI - Non-melanoma skin cancer: new and future synthetic drug treatments.
AB - INTRODUCTION: Non-melanoma skin cancers (NMSC) mainly comprise two different
entities: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC); beneath
these two entities, Merkel cell carcinoma, adnexal tumors, dermatofibrosarcoma
protuberans, angiosarcoma, and cutaneous lymphoma belong to NMSC. These rare skin
tumors are not the topic of this review. BCC and SCC are the most common cancers
diagnosed in humans. The preferred treatment is surgery, which in most cases is
curative. Although a high recurrence rate is seen, these cancers rarely
metastasize. Therefore, systemic treatments were not a priority for these
patients. It is long known that the abnormal activation of Hedgehog and epidermal
growth factor receptor pathways were involved in BCC and SCC. In the last decade,
metastatic disease became an important area of research, mostly because new
therapies that targeted components of these two pathways became available. Areas
covered: Here we cover the available therapeutic options for patients diagnosed
with BCC and SCC, focus on systemic and targeted therapies. Expert opinion: BCC
and SCC are common cancers, with good prognosis. More than the metastatic
disease, advanced local disease and recurrent disease pose clinicians a great
challenge. Albeit there are promising results with targeted therapies, resistance
development has already been described.
PMID- 28414586
TI - Development and Validation of Monoclonal Antibody-Based Antigen Capture ELISA for
Detection of Group A Porcine Rotavirus.
AB - Porcine rotavirus-A (PoRVA) is one of the common causes of mild to severe
dehydrating diarrhea, leading to losses in weaning and postweaning piglets. A
rapid, highly specific, and sensitive antigen-capture enzyme-linked immunosorbent
assay (AC-ELISA) was developed for detection of PoRVA, by using VP6 (a highly
conserved and antigenic protein of group-A rotavirus)-directed rabbit polyclonal
antibodies (capture antibody) and murine monoclonal antibodies (detector
antibody). The detection limit of AC-ELISA was found to be equal to that of
conventional reverse transcription-polymerase chain reaction (RT-PCR; about 102.5
TCID50/mL). For validation of the in-house AC-ELISA, 295 porcine fecal/diarrhea
samples, collected from different provinces of China, were evaluated and compared
with conventional RT-PCR and TaqMan RT-quantitative PCR (qPCR). The sensitivity
and specificity of this in-house AC-ELISA relative to RT-qPCR were found to be
91.67% and 100%, respectively, with the strong agreement (kappa = 0.972) between
these two techniques. Total detection rate with AC-ELISA, conventional RT-PCR,
and RT-qPCR were found to be 11.2%, 11.5%, and 12.2%, respectively, without any
statistical significant difference. Moreover, AC-ELISA failed to detect any cross
reactivity with porcine epidemic diarrhea virus, transmissible gastroenteritis
virus, pseudorabies virus, and porcine circovirus-2. These results suggested that
our developed method was rapid, highly specific, and sensitive, which may help in
large-scale surveillance, timely detection, and preventive control of rotavirus
infection in porcine farms.
PMID- 28414588
TI - Prehospital Predictors of Traumatic Spinal Cord Injury in Victoria, Australia.
AB - OBJECTIVES: To identify the predictors of traumatic spinal cord injury (TSCI) and
describe the differences between confirmed and potential TSCI cases in the
prehospital setting. METHODS: A retrospective cohort study including all adult
patients over a six-year period (2007-12) with potential TSCI who were attended
and transported by Ambulance Victoria (AV). We extracted potential TSCI cases
from the AV data warehouse and linked with the Victorian State Trauma Registry to
compare with final hospital diagnosis. RESULTS: We included a total of 106,059
patients with potential TSCI in the study, with 257 having a spinal cord injury
confirmed at hospital (0.2%). The median [First and third Quartiles] age of
confirmed TSCI cases was 49 [32-69] years, with males comprising 84.1%. Confirmed
TSCI were mainly due to falls (44.8%) and traffic incidents (40.5%). AV spinal
care guidelines had a sensitivity of 100% to detect confirmed TSCI. There were
several factors associated with a diagnosis of TSCI. These were meeting AV
Potential Major Trauma criteria, male gender, presence of neurological deficit,
presence of an altered state of consciousness, high falls (> 3 meters), diving,
or motorcycle or bicycle collisions. CONCLUSION: This study identified several
predictors of TSCI including meeting AV Potential Major Trauma criteria, male
gender, presence of neurological deficit, presence of an altered state of
consciousness, high falls (> 3 meters), diving, or motorcycle or bicycle
collisions. Most of these predictors are included in NEXUS and/or CCR criteria,
however, Potential Major Trauma criteria have not previously been linked to the
presence of TSCI. Therefore, Emergency Medical Systems are encouraged to
integrate similar Potential Major Trauma criteria into their guidelines and
protocols to further improve the provider's accuracy in identifying TSCI and to
be more selective in their spinal immobilization, thereby reducing unwarranted
adverse effects of this practice.
PMID- 28414589
TI - Progesterone Decreases in vitro Indoleamine 2, 3-dioxygenase Expression in
Dendritic and CD4+ Cells from Maternal-Fetal Interface of Rats.
AB - PROBLEM: Several mechanisms contribute to the tolerogenic state observed during
pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO).
This initializes the catabolism of tryptophan, inducing T cells to apoptosis due
to its deprivation and by the action of its catabolites in the placental
microenvironment. Progesterone plays an important part on immunological tolerance
mechanisms during pregnancy; however, there is no evidence it is related to IDO
activity. Thus, this study aimed to investigate progesterone influence on the
maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive
cells by immunophenotyping and flow cytometry under exogenous progesterone
supplementation. METHOD OF STUDY: Placenta and embryo cells were cultured and
separated into groups that received interferon gamma or progesterone,
supplemented or not with mifepristone. After 2 and 24 h, these were labeled with
an anti-IDO and a series of antibodies specific to leucocytes and progesterone
receptor and processed through flow cytometry analysis. RESULTS: Progesterone
induced a significant decrease in the expression of IDO in dendritic cells and
CD4+ lymphocytes. CONCLUSION: The blocking of progesterone receptor on these
cells by mifepristone restored IDO expression levels and may constitute evidence
of the participation of this hormone through a direct route in these cells.
PMID- 28414590
TI - Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery
Disease.
AB - BACKGROUND: Natural killer (NK) cells are the potential modulators of
inflammatory reactions that exert several unique biological effects and could
lead to future adverse events of coronary artery disease (CAD). HYPOTHESIS: The
purpose of this study was to find out the possible association of modulation in
NK cell, TNK cells, T cells, B cells, and tumor necrosis factor alpha (TNF-alpha)
in CAD patients and various forms of myocardial infarction. METHODS: The present
study included total 190 subjects (98 confirmed CAD patients both men and women
and 92 healthy control individuals). Serum concentration of TNF-alpha was
measured by ELISA method. For the measurement of various immune cells, viz., NK
cell, TNK cells, T cells, and B cells, flow-cytometric analysis was performed.
RESULTS: A significant reduction by 15% (P < 0.001) in CD16/CD56 NK cells was
observed in CAD patients. Moreover, non-ST segment elevation myocardial
infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI), unstable
angina (UA), and combined UA + NSTEMI group also showed a significant decline in
NK cells compared with control individuals. CD16/CD56/CD3 TNK cells showed a
significant reduction in CAD, NSTEMI, STEMI, and UA categories. However, UA +
NSTEMI group did not show any significant change in TNK cells. On the other hand,
the level of TNF-alpha was found to be significantly elevated in CAD, STEMI, and
UA groups. NSTEMI and combined UA + NSTEMI group did not show any significant
change in TNF-alpha level. CONCLUSION: Current study provides an insight toward
the association of immune cells and inflammation with CAD.
PMID- 28414592
TI - Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the
Eye.
AB - Diadenosine tetraphosphate abbreviated Ap4A is a naturally occurring
dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic
resistance to enzyme degradation compared to mononucleotides, this molecule can
exhibit profound actions on ocular tissues, including the ocular surface, ciliary
body, trabecular meshwork, and probably the retina. The actions of Ap4A are
mostly carried out by P2Y2 receptors, but the participation of P2X2 and P2Y6 in
processes such as the regulation of intraocular pressure (IOP), together with the
P2Y2, is pivotal. Beyond the physiological role, this dinucleotide can present on
the ocular surface keeping a right production of tear secretion or regulating
IOP. It is important to note that exogenous application of Ap4A to cells or
animal models can significantly modify pathophysiological conditions and thus is
an attractive therapeutic molecule. The ocular location where Ap4A actions have
not been fully elucidated is in the retina. Although some analogues show
interesting actions on pathological situations such as retinal detachment, little
is known about the real effect of this dinucleotide, this being one of the
challenges that require pursuing in the near future.
PMID- 28414591
TI - Violence Victimization, Social Support, and Papanicolaou Smear Outcomes: A
Longitudinal Study from Adolescence to Young Adulthood.
AB - BACKGROUND: African American youth are among those at greatest risk for
experiencing violence victimization. Notably, the mortality rate of cervical
cancer for African American women is also twice that of white women. To date, we
know of no literature using longitudinal data to examine how violence
victimization relates to Papanicolaou (Pap) smear results or cervical cancer in
this population. Our study examines how violence victimization during adolescence
(age 15 to 18) influences psychological distress, perceived social support, heavy
substance abuse, and sexual risk behaviors during emerging adulthood (age 20 to
23), and subsequent Pap smear outcomes during young adulthood (age 29 to 32).
METHOD: This study is based on 12 waves of data collected in a longitudinal study
of 360 African American women from mid-adolescence (ninth grade, mean age = 14.8
years) to young adulthood (mean age = 32.0 years). We used structural equation
modeling analysis to examine the hypothesized model. RESULT: Violence
victimization during adolescence had a direct effect on decreased social support,
increased psychological distress, and increased heavy cigarette use during
emerging adulthood. Better social support was also associated with fewer sexual
partners during emerging adulthood and lower odds of abnormal Pap smear results
during young adulthood. The effect of violence victimization on abnormal Pap
smear was mediated by social support. CONCLUSION: Our results show that violence
victimization during adolescence has long-term negative effects through multiple
pathways that persist into adulthood. Our findings also suggest that social
support may help to compensate against other risk factors. Interventions designed
to address the perceived support may help victims cope with their experience.
PMID- 28414593
TI - Letters to the Editor.
PMID- 28414594
TI - Pathology in Practice.
PMID- 28414595
TI - Advocating for your interests on Capitol Hill.
PMID- 28414596
TI - Anesthesia Case of the Month.
PMID- 28414597
TI - Bovine colostral cells-the often forgotten component of colostrum.
PMID- 28414599
TI - What Is Your Diagnosis?
PMID- 28414600
TI - Pathology in Practice.
PMID- 28414601
TI - Agreement between microscopic examination and bacterial culture of bile samples
for detection of bactibilia in dogs and cats with hepatobiliary disease.
AB - OBJECTIVE To evaluate the agreement between results of microscopic examination
and bacterial culture of bile samples from dogs and cats with hepatobiliary
disease for detection of bactibilia. DESIGN Cross-sectional study. ANIMALS 31
dogs and 21 cats with hepatobiliary disease for which subsequent microscopic
examination and bacterial culture of bile samples was performed from 2004 through
2014. PROCEDURES Electronic medical records of included dogs and cats were
reviewed to extract data regarding diagnosis, antimicrobials administered, and
results of microscopic examination and bacterial culture of bile samples.
Agreement between these 2 diagnostic tests was assessed by calculation of the
Cohen kappa value. RESULTS 17 (33%) dogs and cats had bactibilia identified by
microscopic examination of bile samples, and 11 (21%) had bactibilia identified
via bacterial culture. Agreement between these 2 tests was substantial
(percentage agreement [positive and negative results], 85%; kappa = 0.62; 95%
confidence interval, 0.38 to 0.89) and improved to almost perfect when calculated
for only animals that received no antimicrobials within 24 hours prior to sample
collection (percentage agreement, 94%; kappa = 0.84; 95% confidence interval,
0.61 to 1.00). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that
agreement between microscopic examination and bacterial culture of bile samples
for detection of bactibilia is optimized when dogs and cats are not receiving
antimicrobials at the time of sample collection. Concurrent bacterial culture and
microscopic examination of bile samples are recommended for all cats and dogs
evaluated for hepatobiliary disease.
PMID- 28414602
TI - What Is Your Neurologic Diagnosis?
PMID- 28414603
TI - Cardiovascular findings in ponies with equine metabolic syndrome.
AB - OBJECTIVE To determine whether hypertension, high sympathetic tone, resting and
exercising arrhythmias, and echocardiographic changes consistent with
hypertensive cardiomyopathy were associated with equine metabolic syndrome (EMS)
in ponies. DESIGN Prospective case-control study. ANIMALS 19 privately owned
ponies with a diagnosis of EMS (history of laminitis, body condition score >=
7/9, cresty neck score >= 3/5, and abnormal oral sugar test result; cases) and 20
healthy control ponies. PROCEDURES Heart rate (HR), noninvasively measured
arterial blood pressure (BP), markers of autonomic tone (splenic volume and HR
variability), 24-hour and exercising ECGs, and echocardiograms were compared
between cases and controls. RESULTS Compared with controls, cases had a higher
mean +/- SD HR (44.5 +/- 7.5 beats/min vs 38.6 +/- 6.8 beats/min) and median mean
left ventricular wall thickness (2.0 cm vs 1.8 cm). No differences were
identified between groups in BP, splenic volume, HR variability, and number of
premature complexes in ECGs. Mean wall thickness was correlated with BP (r =
0.54), high-frequency power (r = -0.71), and ratio of low-to high-frequency power
(phi = 0.66). Relative wall thickness was correlated with serum insulin
concentration (r = 0.71). CONCLUSIONS AND CLINICAL RELEVANCE Ponies with EMS had
myocardial hypertrophy that was correlated with insulin response to an oral sugar
test, sympathetic and parasympathetic tone, and BP. The heterogeneity and limited
sample size of this preliminary study should be considered when drawing
conclusions. Cardiovascular changes associated with this syndrome deserve further
attention.
PMID- 28414605
TI - Use of a novel surgical approach for treatment of complete bilateral membranous
choanal atresia in an alpaca cria.
AB - CASE DESCRIPTION A 4-hour-old 6.3-kg (13.9-lb) female alpaca cria was evaluated
because of severe respiratory distress and difficulty nursing since birth.
CLINICAL FINDINGS The cria had open-mouth breathing and cyanotic membranes, with
no airflow evident from either nostril. Supplemental oxygen was delivered, and
the patient was anesthetized and intubated orotracheally; a CT evaluation of the
head confirmed bilateral membranous obstruction of the nasal cavities, consistent
with complete bilateral choanal atresia. TREATMENT AND OUTCOME Choanal atresia
was treated with an endoscopically assisted balloon-dilation technique, and
temporary tracheostomy was performed. Stenosis recurred, requiring revision of
the repair and intranasal stent placement 3 days after the first surgery. The
tracheostomy tube was removed the next day. Complications during hospitalization
included mucoid obstruction of the tracheostomy tube, granulation tissue
development in the trachea near the tracheostomy site, mucoid stent obstruction,
aspiration pneumonia, and presumed partial failure of passive transfer of
immunity. The stents were removed 2 weeks after admission, and the cria was
discharged 3 days later. The owner was advised that the animal should not be
bred. At last follow-up 3 years later, the alpaca was doing well. CLINICAL
RELEVANCE Surgical treatment with a balloon-dilation technique and placement of
nasal stents with endoscopic guidance were curative in this neonatal alpaca with
bilateral membranous choanal atresia. Computed tomography was useful to determine
the nature of the atresia and aid surgical planning. Because a genetic component
is likely, owners should be advised to prevent affected animals from breeding.
PMID- 28414606
TI - Effects of topically applied heterologous serum on reepithelialization rate of
superficial chronic corneal epithelial defects in dogs.
AB - OBJECTIVE To assess the effects of topical application of undiluted heterologous
serum on time to corneal reepithelialization in dogs with superficial chronic
corneal epithelial defects (SCCEDs). DESIGN Multicenter, randomized, double
masked, controlled clinical trial. ANIMALS 41 client-owned dogs. PROCEDURES After
collection of baseline clinical and historical data, dogs were randomly assigned
to receive topically applied undiluted heterologous serum (n = 22) or isotonic
saline (0.9% NaCl) solution (19) along with tobramycin and atropine. Epithelial
debridement (at all visits) and grid keratotomy (at visits 2, 3, and 4) of SCCEDs
were performed. Ophthalmic examination including fluorescein application was
performed once weekly for 4 weeks or until corneal reepithelialization.
Clinicians and owners were masked to treatment group. RESULTS No differences in
baseline data were detected between treatment groups. No difficulties with
medication administration, noncompliance, or adverse reactions were noted. All
SCCEDs in both groups healed by 4 weeks after treatment began. Median time to
reepithelialization (2 weeks) was not significantly different between serum
treated and placebo-treated eyes. Irrespective of treatment group, median time to
reepithelialization was not significantly different for Boxers versus non-Boxer
breeds. Direct correlations were detected between time to reepithelialization and
vascularization score at study entry, vascularization score at time of
reepithelialization, and ulcer area at study entry in both groups. Time to
reepithelialization was not correlated with age, sex, or duration of signs in
either group. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of undiluted
heterologous serum was well tolerated by dogs with SCCEDs but, as an adjunct to
standard treatment, did not reduce time to corneal reepithelialization.
PMID- 28414607
TI - Cardiac arrest in an American Cocker Spaniel during a deep ear flush procedure.
AB - CASE DESCRIPTION A 14-year-old spayed female American Cocker Spaniel with
bilateral otitis media and no evidence of cardiovascular instability was
anesthetized to allow performance of a deep ear flush. CLINICAL FINDINGS
Otoscopic examination of the left ear revealed evidence of chronic inflammation;
the ear was flushed with sterile saline (0.9% NaCl) solution. Examination of the
right ear revealed more severe chronic inflammation than in the left ear,
including a ruptured tympanum (timing of rupture unknown). The right ear was
flushed with sterile saline solution, and several drops of otic medication were
instilled. During infusion of saline solution, the ECG revealed a rapid decrease
in heart rate until no more electrical activity was noted. Pulse also ceased to
be detectable via pulse oximetry and femoral artery palpation. TREATMENT AND
OUTCOME Isoflurane was discontinued immediately after recognition of cardiac
arrest. Shortly after, atropine (0.04 mg/kg [0.02 mg/lb]) and epinephrine (0.3
mg/kg [0.14 mg/lb]) were administered IV, chest compressions and ventilation were
performed for 2 to 3 minutes, and 3 boluses (each 5 mL/kg) of lactated Ringer
solution were administered IV. The dog was extubated 8 minutes after anesthesia
was discontinued, and its recovery was monitored for the next 5 hours. No further
incidents of cardiac arrest occurred after recovery from anesthesia. CLINICAL
RELEVANCE This case represented a rarely documented potential complication
associated with otic manipulation in a dog: cardiac arrest secondary to
stimulation of the auricular branch of the vagus nerve. Veterinarians should be
prepared for and warn clients of this possibility prior to otic flushing.
PMID- 28414609
TI - Association Between Androgen Receptor Splice Variants and Prostate Cancer
Resistance to Abiraterone and Enzalutamide.
PMID- 28414608
TI - Mechanobehavioral Scores in Women with and without TMJ Disc Displacement.
AB - Cartilage fatigue may be a factor in the precocious development of degenerative
changes in the temporomandibular joint (TMJ). This cross-sectional study
estimated potential for cartilage fatigue via TMJ energy densities (ED) and jaw
muscle duty factors (DF), which were combined to calculate mechanobehavioral
scores (MBS) in women with (+) and without (-) bilateral TMJ disc displacement
(DD). All subjects gave informed consent to participate and were examined using
Diagnostic Criteria (DC) for Temporomandibular Disorders (TMD) and magnetic
resonance (MR) and computed tomography (CT) images. Forty-seven subjects were
categorized into +DD ( n = 29) and -DD ( n = 18) groups. Dynamic stereometry (MR
images combined with jaw-tracking data) characterized individual-specific data of
TMJ stress-field mechanics to determine ED (ED = W/ Q mJ/mm3, where W = work
done, Q = volume of cartilage) during 10 symmetrical jaw-closing cycles with a 20
N mandibular right canine load. Subjects were trained to record masseter and
temporalis electromyography over 3 days and 3 nights. Root mean square
electromyography/bite-force calibrations determined subject-specific masseter and
temporalis muscle activities per 20-N bite-force (T20 N, uV), which defined
thresholds. Muscle DF (DF = % duration of muscle activity/total recording time)
were determined for a range of thresholds, and MBS (ED2 * DF) were calculated.
Intergroup differences in ED, DF, and MBS were assessed via analyses of variance
with Bonferroni and Tukey honest significant difference post hoc tests. Average
ED for contralateral TMJs was significantly larger ( P = 0.012) by 1.4-fold in
+DD compared to -DD subjects. Average DF were significantly larger (all P < 0.01)
for +DD compared to -DD subjects by 1.7-, 2.5-, and 1.9-fold for day, night, and
overall, respectively. Daytime MBS were significantly larger (all P < 0.04) by up
to 8.5-fold in +DD compared to -DD subjects. Significantly larger ED, DF, and MBS
were shown in women with compared to women without bilateral TMJ DD.
PMID- 28414611
TI - Population Genetic Structure of Venturia effusa, Cause of Pecan Scab, in the
Southeastern United States.
AB - Venturia effusa is the most important pathogen of pecan in the southeastern
United States. Little information exists on the population biology and genetic
diversity of the pathogen. A hierarchical sampling of 784 isolates from 63 trees
in 11 pecan orchards in the southeastern United States were screened against a
set of 30 previously characterized microsatellite markers. Populations were
collected from Georgia (n = 2), Florida (n = 1), Alabama (n = 2), Mississippi (n
= 1), Louisiana (n = 1), Illinois (n = 1), Oklahoma (n = 1), Texas (n = 1), and
Kansas (n = 1). Clonality was low in all orchard populations (<=10.1% of
isolates), and there were consistently high levels of genotypic diversity
(Shannon-Weiner's index = 3.49 to 4.59) and gene diversity (Nei's measure = 0.513
to 0.713). Analysis of molecular variance showed that, although 81% of genetic
diversity occurred at the scale of the individual tree, 16% occurred between
orchards and only 3% between trees within orchards. All populations could be
differentiated from each other (P = 0.01), and various cluster analyses indicated
that some populations were more closely related compared with other pairs of
populations. This is indicative of some limited population differentiation in V.
effusa in the southeastern United States. Bayesian and nearest-neighbor methods
suggested eight clusters, with orchards from Georgia and Florida being grouped
together. A minimum spanning tree of all 784 isolates also indicated some isolate
identification with source population. Linkage disequilibrium was detected in all
but one population (Kansas), although 8 of the 11 populations had <20% of loci at
disequilibrium. A Mantel test demonstrated a relationship between physical and
genetic distance between populations (Z = 11.9, r = 0.559, P = 0.001). None of
the populations were at mutation-drift equilibrium. All but 3 of the 11
populations had a deficiency of gene diversity compared with that expected at
mutation-drift equilibrium (indicating population expansion); the remaining
populations had an excess of gene diversity compared with that expected at
mutation-drift equilibrium (indicating a recent bottleneck). These observations
are consistent with the known history of pecan and pecan scab, which is that V.
effusa became an issue on cultivated pecan in the last approximately 120 years
(recent population expansion). Recently reported mating type genes and the sexual
stage of this fungus may help explain the observed population characteristics,
which bear a strong resemblance to those of other well-characterized sexually
reproducing ascomycete pathogens.
PMID- 28414610
TI - Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An
Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en
Cancerologie Digestive Database.
AB - Purpose Factors contributing to early mortality after initiation of treatment of
metastatic colorectal cancer are poorly understood. Materials and Methods Data
from 22,654 patients enrolled in 28 randomized phase III trials contained in the
ARCAD (Aide et Recherche en Cancerologie Digestive) database were pooled.
Multivariable logistic regression models for 30-, 60-, and 90-day mortality were
constructed, including clinically and statistically significant patient and
disease factors and interaction terms. A calculator (nomogram) for 90-day
mortality was developed and validated internally using bootstrapping methods and
externally using a 10% random holdout sample from each trial. The impact of early
progression on the likelihood of survival to 90 days was examined with time
dependent Cox proportional hazards models. Results Mortality rates were 1.4% at
30 days, 3.4% at 60 days, and 5.5% at 90 days. Among baseline factors, advanced
age, lower body mass index, poorer performance status, increased number of
metastatic sites, BRAF mutant status, and several laboratory parameters were
associated with increased likelihood of early mortality. A multivariable model
for 90-day mortality showed strong internal discrimination (C-index, 0.77) and
good calibration across risk groups as well as accurate predictions in the
external validation set, both overall and within patient subgroups. Conclusion A
validated clinical nomogram has been developed to quantify the risk of early
death for individual patients during initial treatment of metastatic colorectal
cancer. This tool may be used for patient eligibility assessment or risk
stratification in future clinical trials and to identify patients requiring more
or less aggressive therapy and additional supportive measures during and after
treatment.
PMID- 28414612
TI - Multimodal Imaging in Masquerade Syndromes.
AB - Masquerade syndromes present to uveitis clinics due to the appearance of
inflammatory signs and chronic symptoms that are not responsive to conventional
treatment. They are frequently misdiagnosed and treated as refractory
inflammatory conditions, which delays appropriate diagnosis and management. This
review of literature focuses on the commonly encountered masquerade syndromes and
discusses the role of multimodal imaging in addressing these complex clinical
presentations. We review the conventional imaging techniques for these patients
and discuss emerging technological advances that may help in establishing a
diagnosis. We present cases highlighting the utility of multimodal imaging in
identifying the etiology.
PMID- 28414613
TI - Sympathetic Ophthalmia.
PMID- 28414614
TI - Intracorporeal Circular Stapled Esophagojejunostomy Using Conventional Purse
String Suture Instrument After Laparoscopic Total Gastrectomy.
AB - BACKGROUND: An optimal alimentary tract reconstruction technique after
laparoscopic total gastrectomy (LTG) remains controversial. The authors developed
a new simple technique for intracorporeal esophagojejunal anastomosis that
employs a conventional purse-string suture instrument (PSI) and circular stapler.
METHODS: From May 2014 to April 2016, 41 consecutive patients with gastric cancer
underwent LTG in the author's institution. Intracorporeal esophagojejunal
anastomosis using the following method was attempted for all patients. After
total gastrectomy was completed laparoscopically, a small vertical incision
(about 40 mm) was created at the left midclavicular line and retracted by a wound
retractor. An anvil of a 25 mm circular stapler was introduced into the abdominal
cavity. Then a previously prepared surgical glove, which was cut open at the
thumb and the little finger through which the two hand shafts of the PSI were
passed separately and sealed by ties, was attached to the wound retractor to
maintain airtightness, and the PSI was introduced into the abdominal cavity. The
following procedure was similar to conventional open surgery except that it was
performed under laparoscopic vision. RESULTS: Intracorporeal esophagojejunal
anastomosis was performed successfully for all 41 patients. No case required
extension of the initial incision for difficulties during anastomosis. The mean
operation time was 245 minutes, and the mean time for the purse-string suture and
anvil placement was 15 minutes. Tumor-free margins were achieved in all 41
patients. There were no anastomosis-related complications or other major surgical
complications. CONCLUSIONS: With the described method, intracorporeal
esophagojejunal anastomosis can be performed easily and safely.
PMID- 28414615
TI - Virulence profile: Juliana Campos Junqueira.
PMID- 28414617
TI - Theorizing the Impact of Targeted Narratives: Model Admiration and Narrative
Memorability.
AB - Communication campaigns often include components that have been designed for a
specific population, a strategy referred to as targeting. Targeted narratives are
story-based components of a campaign that feature a character or situation
relevant to the intended audience. Though commonplace, few studies have
explicated the underlying mechanisms by which targeted narratives exert
influence. In a message evaluation study, 316 women aged 40-75 (Mage = 51.19, SD
= 8.11) were exposed to one of two targeted narratives and asked to complete
measures of model admiration, narrative memorability, and intentions to receive a
mammography. Targeting was based upon affiliation with the Mormon church. The
results revealed that the relationship between the targeted narratives and
screening intentions was especially strong for women from the target population
who admired the depicted models and found the stories memorable.
PMID- 28414616
TI - Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue
Engineered Cartilage Constructs Across Testing Platforms.
AB - Cartilage tissue engineering is emerging as a promising treatment for
osteoarthritis, and the field has progressed toward utilizing large animal models
for proof of concept and preclinical studies. Mechanical testing of the
regenerative tissue is an essential outcome for functional evaluation. However,
testing modalities and constitutive frameworks used to evaluate in vitro grown
samples differ substantially from those used to evaluate in vivo derived samples.
To address this, we developed finite element (FE) models (using FEBio) of
unconfined compression and indentation testing, modalities commonly used for such
samples. We determined the model sensitivity to tissue radius and subchondral
bone modulus, as well as its ability to estimate material parameters using the
built-in parameter optimization tool in FEBio. We then sequentially tested
agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation
platform, followed by unconfined compression. Similarly, we evaluated the ability
of the model to generate material parameters for living constructs by evaluating
engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 * 107
cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a
chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested
sequentially in indentation and unconfined compression. The model successfully
completed parameter optimization routines for each testing modality for both
acellular and cell-based constructs. Traditional outcome measures and the FE
derived outcomes showed significant changes in material properties during the
maturation of engineered cartilage tissue, capturing dynamic changes in
functional tissue mechanics. These outcomes were significantly correlated with
one another, establishing this FE modeling approach as a singular method for the
evaluation of functional engineered and native tissue regeneration, both in vitro
and in vivo.
PMID- 28414618
TI - Understanding Spanish-Language Response in a National Health Communication
Survey: Implications for Health Communication Research.
AB - : Spanish-speaking Latinos account for 13% of the U.S. population yet are
chronically under-represented in national surveys; additionally, the response
quality suffers from low literacy rates and translation challenges. These are the
same issues that health communicators face when understanding how best to
communicate important health information to Latinos. The Health Information
National Trends Survey (HINTS) offers a unique opportunity to understand the
health communication landscape and information needs of the U.S. POPULATION: We
describe the challenges in recruiting Spanish-speaking HINTS respondents and
strategies used to improve rates and quality of responses among Spanish-speaking
Latinos. Cognitive interviewing techniques helped to better understand how
Spanish-speaking Latinos were interpreting the survey questions, and the extent
to which these interpretations matched English-speaking respondents'
interpretations. Some Spanish-speaking respondents had difficulty with the
questions because of a lack of access to health care. Additionally, Spanish
speaking respondents had a particularly hard time answering questions that were
presented in a grid format. We describe the cognitive interview process, and
consider the impact of format changes on Spanish-speaking people's responses and
response quality. We discuss challenges that remain in understanding health
information needs of non-English-speakers.
PMID- 28414619
TI - How the nerves reached the muscle: Bernard Katz, Stephen W. Kuffler, and John C.
Eccles-Certain implications of exile for the development of twentieth-century
neurophysiology.
AB - This article explores the work by Bernard Katz (1911-2003), Stephen W. Kuffler
(1913-1980), and John C. Eccles (1903-1997) on the nerve-muscle junction as a
milestone in twentieth-century neurophysiology with wider scientific
implications. The historical question is approached from two perspectives: (a) an
investigation of twentieth-century solutions to a longer physiological dispute
and (b) an examination of a new kind of laboratory and academic cooperation. From
this vantage point, the work pursued in Sydney by Sir John Carew Eccles' team on
the neuromuscular junction is particularly valuable, since it contributed a
central functional element to modern physiological understanding regarding the
function and structure of the human and animal nervous system. The reflex model
of neuromuscular action had already been advanced by neuroanatomists such as
Georg Prochaska (1749-1820) in Bohemia since the eighteenth century. It became a
major component of neurophysiological theories during the nineteenth century,
based on the law associated with the names of Francois Magendie (1783-1855) in
France and Charles Bell (1774-1842) in Britain regarding the functional
differences of the sensory and motor spinal nerves. Yet, it was not until the
beginning of the twentieth century that both the histological and the
neurophysiological understanding of the nerve-muscle connection became entirely
understood and the chemical versus electrical transmission further elicited as
the mechanisms of inhibition. John C. Eccles, Bernard Katz, and Stephen W.
Kuffler helped to provide some of the missing links for modern neurophysiology.
The current article explores several of their scientific contributions and
investigates how the context of forced migration contributed to these
interactions in contingently new ways.
PMID- 28414621
TI - The American Association of Occupational Health Nurses: Seventy-Five Years of
Education, Practice, and Research.
AB - For the past 75 years, the American Association of Industrial Nurses, and later
the American Association of Occupational Health Nurses, has advocated for
occupational and environmental health nurses by supporting quality undergraduate
and graduate education in the specialty and certification through the American
Board of Occupational Health Nurses, Inc., and providing funding for and
dissemination of occupational health nursing research as well as by developing
occupational health nursing practice standards, competencies, and code of ethics.
PMID- 28414622
TI - Clostridium difficile Infection.
AB - Preventing Clostridium difficile, the most common cause of health care-associated
infections in hospitals and infectious disease death in the United States, is a
national priority. Increased rates of infection among low-risk individuals in the
community call for community-based prevention efforts to halt the increasing
spread of this highly contagious opportunistic infection.
PMID- 28414623
TI - Licensed Practical/Vocational Nurses: A Place on the Team.
PMID- 28414624
TI - History, Passion, and Performance.
AB - History, Passion, and Performance was chosen as the theme for the 75th
anniversary of the American Association of Occupational Health Nurses (AAOHN)
kickoff. The American Association of Occupational Health Nurses has a long
history created by passionate, dedicated members. This article highlights
historical foundations of the Association, describes the occupational health
nurse's passion to drive quality care for workers and discusses future
professional and organizational challenges.
PMID- 28414625
TI - Advancing Well-Being Through Total Worker Health(r).
AB - Total Worker Health(r) (TWH) is a paradigm-shifting approach to safety, health,
and well-being in the workplace. It is defined as policies, programs, and
practices that integrate protection from work-related safety and health hazards
with promotion of injury and illness prevention efforts to advance worker well
being. The most current TWH concepts are presented, including a description of
issues relevant to TWH and introduction of a hierarchy of controls applied to
TWH. Total Worker Health advocates for a foundation of safety and health through
which work can contribute to higher levels of well-being.
PMID- 28414626
TI - The Future of Occupational Health Nursing in a Changing Health Care System.
AB - Repealing the Affordable Care Act (ACA) has significant implications for the
future of occupational health nursing practice. As changes are proposed and
implemented, occupational health nurses must continue to prioritize preventive
care, chronic disease management, healthy communities, environmental health, and
sustainability. In particular, immigrant workers are a vulnerable population
needing attention by occupational health nurses.
PMID- 28414627
TI - The Dangers of Electrosurgical Smoke to Operating Room Personnel: A Review.
AB - A 2007 study in the United Kingdom showed that three of 98 surgeons surveyed
admitted using dedicated smoke extractors; 72% of respondents believed inadequate
precautions were in place to protect staff from the potential dangers of
electrosurgical smoke. Surgical smoke contains harmful chemicals (e.g., hydrogen
cyanide, acetylene, and butadiene) that can circumvent standard masks used in the
operating room (OR). In addition, bacteria and viruses can be transmitted through
this smoke. The topic of electrosurgical smoke is important to occupational
health nurses not only because of their responsibility to protect workers, but
also because they, like other health care providers, may be exposed to smoke
routinely. The authors of this review recommend the regular use of smoke
evacuation in ORs and avoidance of electrosurgery whenever possible to protect OR
personnel from the potential long-term harmful effects of electrosurgical smoke.
PMID- 28414628
TI - Fried Green Tomatoes and The Color Purple: A case study in lesbian friendship and
cultural controversy.
AB - Published in the 1980s, Fannie Flagg's Fried Green Tomatoes at the Whistle Stop
Cafe and Alice Walker's The Color Purple are lesbian coming-of-age narratives
that share a great deal in common in terms of their thematic content, publication
histories, and cultural afterlives. In both novels, female friendships are shaped
by patriarchal violence and develop in the context of the rural, segregated,
early twentieth-century U.S. South. But the two novels also diverge in
significant ways, as differences in race, gender, class, and sexuality shape
their protagonists' experiences of love and friendship. As filmmakers Steven
Spielberg and Jon Avnet adapted these novels for the screen, they made decisions
about how to portray the texts' representations of homoerotic friendship and same
sex love. Both films generated significant cultural controversy as a result,
particularly as some viewers claimed that the films elided the novels'
representations of lesbian sexuality. Building upon recent scholarship in
critical race theory, queer theory, and friendship studies, I argue that Walker's
and Flagg's representations of queer friendship, a term that I describe in more
detail throughout the essay, subvert dominant classifications of romantic,
familial, and platonic love. By comparatively analyzing the American public's
reception of the two film adaptations in conjunction with close readings of
scenes from the novels and films, I reveal how representations of queer
friendship not only catalyze cultural controversy, but also serve as a vehicle of
social criticism.
PMID- 28414629
TI - Effects of chemotherapy on the health-related quality of life of Japanese lower
rectal cancer patients after sphincter-saving surgery.
AB - We examined the effects of adjuvant chemotherapy on the health-related quality of
life (HRQOL) of lower rectal cancer patients receiving sphincter-saving surgery
(SSS). In all, 109 patients completed a questionnaire before surgery and 1, 6,
and 12 months afterwards. In the chemotherapy group, physical and social
functioning scores were significantly lower 12 months after surgery compared with
the nonchemotherapy group. These effects of adjuvant chemotherapy suggest that a
different clinical approach might more effectively improve physical and social
functioning in lower-rectal cancer patients undergoing chemotherapy. Healthcare
providers should be alert for adverse events in patients with lower-rectal cancer
and promptly address such conditions.
PMID- 28414630
TI - Infection Courts in Watermelon Plants Leading to Seed Infestation by Fusarium
oxysporum f. sp. niveum.
AB - Fusarium wilt incited by Fusarium oxysporum f. sp. niveum is a seed-transmitted
disease that causes significant yield loss in watermelon production. The pathogen
may infect watermelon seeds latently, which can be an important inoculum source
and contribute to severe disease outbreak. However, information regarding
infection courts of F. oxysporum f. sp. niveum leading to infestation of
watermelon seeds is limited. To determine how seeds in watermelon fruit can be
infested by F. oxysporum f. sp. niveum during the watermelon growing season,
greenhouse and field experiments were conducted in 2014 and 2015 where watermelon
flowers and immature fruit were inoculated with F. oxysporum f. sp. niveum. Seeds
were extracted from mature watermelon fruit, and infestation of watermelon seeds
was determined by isolation of F. oxysporum f. sp. niveum and further confirmed
by real-time polymerase chain reaction (PCR) analysis. Inoculation of the
pericarp of immature fruit resulted in 17.8 to 54.4% of infested seeds under
field conditions and 0.6 to 12.8% of infested seeds under greenhouse conditions
when seeds were not surface disinfested prior to isolation. Seed infestation was
also detected in 0 to 4.5% of the seeds when seeds were surface disinfested prior
to isolation. Inoculation of pistil resulted in 0 to 7.2% and 0 to 18.3% of
infested seeds under greenhouse and field conditions when seeds were surface
disinfested or not disinfested before isolation, respectively. Inoculation of
peduncle resulted in 0.6 to 6.1% and 0 to 10.0% of infested seeds in the
greenhouse and field experiments when seeds were surface disinfested or not
disinfested before isolation, respectively. Seed infestation was also detected in
all the experiments using real-time PCR assay when pericarp or pistil was
inoculated, and in three of four experiments when peduncle was inoculated,
regardless of whether seeds were surface disinfested or not disinfested. Pericarp
and peduncle of immature watermelon fruit and pistil of watermelon flowers could
be potential infection courts for F. oxysporum f. sp. niveum leading to
infestation of seeds in asymptomatic watermelon fruit.
PMID- 28414631
TI - Rathayibacter toxicus, Other Rathayibacter Species Inducing Bacterial Head Blight
of Grasses, and the Potential for Livestock Poisonings.
AB - Rathayibacter toxicus, a Select Agent in the United States, is one of six
recognized species in the genus Rathayibacter and the best known due to its
association with annual ryegrass toxicity, which occurs only in parts of
Australia. The Rathayibacter species are unusual among phytopathogenic bacteria
in that they are transmitted by anguinid seed gall nematodes and produce
extracellular polysaccharides in infected plants resulting in bacteriosis
diseases with common names such as yellow slime and bacterial head blight. R.
toxicus is distinguished from the other species by producing corynetoxins in
infected plants; toxin production is associated with infection by a
bacteriophage. These toxins cause grazing animals feeding on infected plants to
develop convulsions and abnormal gate, which is referred to as "staggers," and
often results in death of affected animals. R. toxicus is the only recognized
Rathayibacter species to produce toxin, although reports of livestock deaths in
the United States suggest a closely related toxigenic species may be present. A
closely related but undescribed species, Rathayibacter sp. EV, originally
isolated from Ehrharta villosa var. villosa in South Africa, is suspected of
producing toxin. Many of the diseases caused by Rathayibacter species occur in
arid areas and the extracellular polysaccharide they produce is believed to aid
in their survival between crops. For example, R. "agropyri" was isolated from
infected plant material after being stored for 50 years in a herbarium.
Similarly, the anguinid vectors associated with these bacteria form seed galls in
infected plants and are capable of surviving for very long periods of time under
dry conditions. The addition of R. toxicus to the list of Select Agents has
raised concern over its potential introduction and a realization that current
diagnostic methods are inadequate to distinguish among Rathayibacter species. In
addition, little is known about the Rathayibacter species and their seed gall
nematode vectors present in the United States.
PMID- 28414632
TI - Analysis of the Spatial Pattern of Strawberry Angular Leaf Spot in California
Nursery Production.
AB - In California, angular leaf spot (ALS) is a common disease in strawberry nursery
production, and a major concern for nurseries wishing to export plants. As the
spatial pattern of a disease can offer insight into pathogen source, mode of
dissemination, and how current crop management practices affect epidemic
development, an understanding of the spatial pattern of ALS would allow nursery
growers to make informed decisions regarding disease management. Ninety-seven
field assessments of disease incidence were performed at different nursery
locations in 2014 and 2015 to quantify ALS spatial pattern under commercial
conditions. Both point-pattern and geostatistical statistical procedures were
used to analyze the data. The spatial pattern of ALS was characterized by a high
degree of heterogeneity, as indicated by high median values of the beta-binomial
distribution's theta parameter (0.643), and the index of dispersion, D (4.218).
The binary power law provided a robust description of the data with estimated
slope and intercept parameters significantly greater than 1 and 0, respectively
(P < 0.001). Spatial analysis by distance indices (SADIE) detected significant
nonrandom spatial arrangements for 64% of the data sets. Analysis of directional
disease spread showed a strong spatial association between sampling units along
the same planting row. This suggests that recurrent crop operations during the
growing season play a significant role in ALS spread and should be taken into
account to improve disease control.
PMID- 28414633
TI - Genome-Wide Analysis Provides Evidence on the Genetic Relatedness of the Emergent
Xylella fastidiosa Genotype in Italy to Isolates from Central America.
AB - Xylella fastidiosa is a plant-pathogenic bacterium recently introduced in Europe
that is causing decline in olive trees in the South of Italy. Genetic studies
have consistently shown that the bacterial genotype recovered from infected olive
trees belongs to the sequence type ST53 within subspecies pauca. This genotype,
ST53, has also been reported to occur in Costa Rica. The ancestry of ST53 was
recently clarified, showing it contains alleles that are monophyletic with those
of subsp. pauca in South America. To more robustly determine the phylogenetic
placement of ST53 within X. fastidiosa, we performed a comparative analysis based
on single nucleotide polymorphisms (SNPs) and the study of the pan-genome of the
27 currently public available whole genome sequences of X. fastidiosa. The
resulting maximum-parsimony and maximum likelihood trees constructed using the
SNPs and the pan-genome analysis are consistent with previously described X.
fastidiosa taxonomy, distinguishing the subsp. fastidiosa, multiplex, pauca,
sandyi, and morus. Within the subsp. pauca, the Italian and three Costa Rican
isolates, all belonging to ST53, formed a compact phylotype in a clade divergent
from the South American pauca isolates, also distinct from the recently described
coffee isolate CFBP8072 imported into Europe from Ecuador. These findings were
also supported by the gene characterization of a conjugative plasmid shared by
all the four ST53 isolates. Furthermore, isolates of the ST53 clade possess an
exclusive locus encoding a putative ATP-binding protein belonging to the family
of histidine kinase-like ATPase gene, which is not present in isolates from the
subspecies multiplex, sandyi, and pauca, but was detected in ST21 isolates of the
subspecies fastidiosa from Costa Rica. The clustering and distinctiveness of the
ST53 isolates supports the hypothesis of their common origin, and the limited
genetic diversity among these isolates suggests this is an emerging clade within
subsp. pauca.
PMID- 28414635
TI - Ann Veronica Janssens: yellowbluepink.
PMID- 28414634
TI - Detection of the Canine Parvovirus 2c Subtype in Australian Dogs.
AB - Canine parvovirus (CPV-2) is an important cause of hemorrhagic enteritis in dogs.
In Australia the disease has been associated with CPV-2a and CPV-2b variants. A
third more recently emerged variant overseas, CPV-2c, has not been detected in
surveys of the Australian dog population. In this study, we report three cases of
canine parvoviral enteritis associated with CPV-2c infection; case 1 occurred in
an 8-week-old puppy that died following acute hemorrhagic enteritis. Cases 2 and
3 were an 11-month-old female entire Saint Bernard and a 9-month-old male entire
Siberian husky, respectively, both which had completed vaccination schedules and
presented with vomiting or mild diarrhea only. Full genomic sequencing of
parvoviral DNA from cases 1, 2, and 3 revealed greater than 99% homology to known
CPV-2c variants and predicted protein sequences from the VP2 region of viral DNA
from all three cases identified; glutamic acid residues at the 426 amino acid
residue, characteristic of the CPV-2c variant. Veterinary professionals should be
aware that CPV-2c is now present in Australia, detected in a puppy and vaccinated
young adult dogs in this study. Further characterization of CPV-2c-associated
disease and its prevalence in Australian dogs requires additional research.
PMID- 28414636
TI - Connectome: dancing through neuronal circuits.
PMID- 28414637
TI - Lessons learned from Christmas lectures.
PMID- 28414638
TI - An orange and Alzheimer's disease?
PMID- 28414639
TI - Memory, distraction, and nostalgia.
PMID- 28414640
TI - Richard Morris' Christmas lecture double-bill.
PMID- 28414641
TI - Vascular disease and neurodegeneration: advancing together.
PMID- 28414642
TI - Disease progression in LRRK2 parkinsonism.
PMID- 28414643
TI - Optimisation of stroke research.
PMID- 28414644
TI - Corrections.
PMID- 28414645
TI - Diagnosis and classification of optic neuropathies.
PMID- 28414646
TI - Membrane damage is at the core of Alzheimer's disease.
PMID- 28414647
TI - Diagnosis and classification of optic neuropathies - Authors' reply.
PMID- 28414648
TI - Remi W Bouchard, a pioneer in behavioural neurology.
PMID- 28414649
TI - Gaining ground against cerebral malaria.
PMID- 28414650
TI - Edor Kabashi.
PMID- 28414651
TI - Historical landmarks in dementia with Lewy bodies.
PMID- 28414652
TI - No past, no future: studies in the art and science of memory.
PMID- 28414653
TI - Increasing value and reducing waste in stroke research.
AB - Stroke is a major burden to patients and society, and resources spent on stroke
research must be used efficiently and produce good value in terms of improvements
in human health. However, many instances of poor value from stroke research
funding have resulted from the way in which stroke research topics have been
chosen and how studies have been designed, conducted, analysed, regulated,
managed, disseminated, or reported. A cooperative effort of European stroke
researchers aimed to identify sources of inefficiency and waste, recommend
approaches to increase value, and highlight examples of best practice in stroke
research. Evidence suggests that progress has been made, but there is room for
much improvement; researchers, funders, regulators, and other stakeholders in
stroke research might consider these recommendations when planning new research.
PMID- 28414654
TI - Left ventricular function determines the survival benefit for women over men
after transcatheter aortic valve implantation (TAVI).
AB - AIMS: There is evidence for a lower mortality in female patients after
transcatheter aortic valve implantation (TAVI), but the underlying reasons for
the gender-specific differences in prognosis are not well understood. In
particular, the role of left ventricular dysfunction is unclear. In this study,
we addressed the question of whether differences in left ventricular ejection
fraction (LVEF) could account for the gender benefit for female TAVI patients.
METHODS AND RESULTS: From January 2011 to December 2013, a total of 15,616
patients treated with TAVI were prospectively enrolled in the German Aortic Valve
Registry (GARY). For the present analysis, female TAVI patients (N=8,456) were
compared with male TAVI patients (N=7,160) with a particular focus on LVEF.
Mortality at one year was 18.1% in women and 22.6% in men (p<0.001). Multivariate
analysis also revealed that female gender was associated with a lower one-year
mortality (adjusted hazard ratio [HR] 0.88 [0.81-0.95]). There was no difference
in gender-specific mortality in patients with baseline LVEF >50% (women: 16.4%;
men 17.6%, p=0.268), but in patients with LVEF 30%-50% (21.0% versus 25.7%,
p<0.001) and <30% (26.2% versus 37.6%, p<0.001) one-year mortality was
significantly lower in women than in men. CONCLUSIONS: The survival benefit for
women over men after TAVI was only observed in patients with a preprocedural LVEF
<=50%.
PMID- 28414655
TI - Effect of early percutaneous coronary intervention on one-year risk of pneumonia
and pneumonia-related adverse outcomes in patients with acute myocardial
infarction.
AB - AIMS: The aim of this study was to investigate the association between early
percutaneous coronary intervention (PCI) and pneumonia risk in patients with
acute myocardial infarction (AMI) by using Taiwan's National Health Insurance
Research Database (NHIRD). METHODS AND RESULTS: In total, 4,732 patients with non
ST-elevation myocardial infarction (NSTEMI) and 5,465 with ST-elevation
myocardial infarction (STEMI) who had received PCI during AMI hospitalisation
(early PCI) were evaluated. Patients who did not receive PCI during AMI
hospitalisation (deferred PCI) were matched through propensity score matching.
The incidence rates (per 100 person-months) of pneumonia hospitalisation,
pneumonia-related respiratory failure, and pneumonia-related death associated
with early PCI in patients with NSTEMI were 0.36 (95% confidence interval [CI]:
0.32-0.42), 0.12 (95% CI: 0.10-0.16), and 0.08 (95% CI: 0.06-0.11), respectively.
In patients with STEMI, the incidence rates (per 100 person-months) of the
aforementioned adverse events were 0.16 (95% CI: 0.13-0.20), 0.04 (95% CI: 0.03
0.06), and 0.02 (95% CI: 0.01-0.04), respectively. After adjustment for patients'
clinical variables, early PCI was associated with reduced risks of pneumonia
hospitalisation (adjusted hazard ratio [aHR] 0.54, 95% CI: 0.43-0.68, p<0.001),
pneumonia-related respiratory failure (aHR 0.54, 95% CI: 0.35-0.84, p=0.006), and
pneumonia-related death (aHR 0.29, 95% CI: 0.17-0.52, p<0.001) in patients with
NSTEMI. In patients with STEMI, early PCI was beneficial for pneumonia
hospitalisation (aHR 0.62, 95% CI: 0.45- 0.86, p=0.004). CONCLUSIONS: Early PCI
might reduce the risk of pneumonia hospitalisation in patients with AMI.
PMID- 28414656
TI - Prevalence and outcomes of coronary artery perforation during percutaneous
coronary intervention.
AB - AIMS: We aimed to examine the prevalence, clinical outcomes and procedural
characteristics of percutaneous coronary intervention (PCI) complicated by
coronary artery perforation (CAP) in a contemporary patient population. METHODS
AND RESULTS: Procedural records of 39,115 patients undergoing PCI between 2005
and 2016 were reviewed. CAP affected 149 cases (0.37%). The prevalence of CAP
increased from 0.31% in 2005 to 0.45% in 2016 (p=0.03), reflecting an increase in
more complex PCI (from 14% in 2005 to 21% in 2016; p<0.0001). CAP was associated
with increased all-cause mortality (23.1% vs. 9.4% in those without perforation;
p=0.0054) and was an independent predictor of mortality (HR 2.55; 95% CI: 1.34
4.78). In-patient mortality was 4% (6/149). In 43 of 149 (28.9%) cases, a
significant pericardial effusion ensued and mortality rates were higher in this
subgroup. Thirty-one patients had covered stents (CS) inserted and five did not
survive to discharge. Of the 26 patients with a CS who survived to hospital
discharge, six (23.1%) had definite stent thrombosis, and two (7.7%) had
possible/probable stent thrombosis. CONCLUSIONS: CAP remains uncommon but the
prevalence is increasing. CAP is associated with significant short- and long-term
mortality, particularly when there is haemodynamic compromise necessitating
pericardiocentesis. Covered stents are a valuable tool but they are associated
with a high risk of stent thrombosis.
PMID- 28414657
TI - Death by Propofol.
AB - Since its introduction in 1986, propofol ( two, 6-diisopropylphenol) , an
intravenous sedative-hypnotic agent, has been utilized for the induction and
maintenance of general anesthesia and conscious sedation in over 80 percent of
cases; largely replacing thiopental ( sodium pentothal) over a decade ago.
Unrestricted as a controlled substance, propofol's abuse potential emerged
quickly and was highlighted by the death of pop singer, Michael Jackson, in 2009.
In order to assess the epidemiological features of fatal propofol abuse, a
descriptive analysis of the scientific literature was conducted using Internet
search engines. Well-documented cases of fatal propofol abuse were stratified as
unintentional or accidental deaths and as intentional deaths by suicides or
homicides. Continuous variables were compared for differences by unpaired, two
tailed t-tests with statistical significance indicated by p-values less than
0.05. Of 21 fatal cases of propofol abuse, 18 (86 percent ) occurred in
healthcare workers, mostly anesthesiologists and nurse anesthetists (n=14, 67
percent ). One case occurred in a layman who purchased propofol on the Internet.
Seventeen deaths (81 percent ) were accidental; two were suicides (9.5 percent )
and two were homicides (9.5 percent ). Blood levels in intentional death cases
were significantly greater than in accidental death cases (p less than 0.0001)
all of which reflected initial therapeutic induction-level doses in the ranges of
2.0-2.5 mg/kg. Though lacking in analgesic effects, the abuse of propofol by
young healthcare professionals, particularly operating room workers, has been
significant; and likely underreported. Propofol is a dangerous drug with an
evident abuse potential which often results in fatalities.
PMID- 28414658
TI - Septic Cerebral Venosinus Thrombosis Secondary to an Odontogenic Infection.
AB - BACKGROUND: Cerebral venosinus thrombosis (CVT); is an uncommon, potentially
fatal disease that is more common in young adults and children. Thrombophilia,
elevated estrogenic states, and infections are the most common risk factors in
patients who develop CVT. CASE: A 69-year-old man with a right-sided odontogenic
infection presented with fever, headache, opthalmoplegia, and periorbital
swelling. Imaging revealed evidence of meningitis and thrombosis of bilateral
ophthalmic veins, the cavernous sinus, right internal jugular vein, and sigmoid
sinus. The patient was treated with empiric antibiotic therapy and unfractionated
heparin. He recovered with only mild impairment in right eye abduction.
DISCUSSION: Early diagnosis and prompt treatment of CVT is vital in reducing the
associated morbidity and mortality. Unfractionated or low molecular weight
heparin may be safely used in CVT patients. Thrombolytic therapy is an option in
clinically severe cases. Treatment also includes addressing the underlying cause
and management of early complications.
PMID- 28414659
TI - Knowledge of HPV-Related Oropharyngeal Cancer and Use of Human Papillomavirus
Vaccines by Pediatricians in Louisiana.
AB - OBJECTIVES: To determine the level of knowledge of HPV related oropharyngeal
cancer and practice patterns of HPV vaccine use by pediatricians. STUDY DESIGN,
SUBJECTS, METHODS: IRB approved 18-question survey was administered to members of
the Louisiana Chapter of the American Academy of Pediatrics. RESULTS: We received
116 responses (response rate: 15.9 percent );. 104 respondents (89.66 percent );
routinely recommend/offer HPV vaccine, 6 (5.17 percent ); occasionally or only at
caregiver request, and 6 (5.17 percent ); do not offer the vaccine. 17 (15.5
percent ); reported having no awareness of the link between oropharyngeal cancer
and HPV, and only 50 (45.9 percent ); had knowledge that HPV-related
oropharyngeal cancer incidence was increasing. Strength of recommendation for
males and knowledge of HPV-related oropharyngeal cancer were not associated with
years in practice, practice type or patient population served. CONCLUSIONS:
Increased awareness regarding HPV-related oropharyngeal cancers among primary
care providers may increase HPV immunization rates, especially in males.
PMID- 28414660
TI - A Mullerian Cyst Resected From the Posterior Mediastinum.
AB - Differential diagnoses of mediastinal masses are often based on the anatomic
locations. Traditionally the posterior mediastinum has been home to esophageal
and neurogenic cysts, but a new entity has been found to be prevalent since its
initial report in 2005: the Mullerian cyst. We present a 49-year-old with history
of cough who was found to have such a mass. We will discuss the surgical outcome
and the details of this interesting entity. The literature pertinent to this type
of cyst will be evaluated. In all cases reported, the literature demonstrates
that surgical removal results in uneventful follow-up with no evidence of
malignancy or cyst recurrence.
PMID- 28414661
TI - Delayed Presentation of Tuberour Sclerosis Complex in Adult Women.
AB - INTRODUCTION: Tuberous sclerosis complex (TSC); is an autosomal dominant disorder
characterized by the formation of hamartomatous lesions in multiple organs, with
a birth incidence of around one in 10,000. Although it usually manifests itself
in early life, we present a case of an adult woman who we diagnosed with TSC.
CASE: A 27 year old woman presented to Emergency Department with worsening right
flank pain and progressive dyspnea. Physical examination findings revealed
Shagreen patches and multiple angiomyolipomas of the skin. Computed tomography
scan of the chest and abdomen was remarkable for pulmonary
lymphangioleiomyomatosis and renal angiomyolipomas. Brain imaging revealed
multiple subependymal nodules and cortical dysplasias. Subsequent genetic testing
later confirmed pathogenic mutation in the TSC2 gene and patient was referred for
Genetic counseling and further management. DISCUSSION: Clinical features of TSC
continue to be the principal means of diagnosis, with the inclusion of
identification of a pathogenic mutation in TSC1 and TSC2 as an independent
diagnostic criterion. Affected patients may present early in life with the
classic triad of seizures, intellectual disability, and cutaneous angiofibromas,
but some findings, notably renal angiomyolipomas and pulmonary
lymphangioleiomyomatosis (LAM);, emerge later, placing adults with undiagnosed
TSC at increased risk for morbidity and mortality. Recent advances in the
treatment of TSC highlight.
PMID- 28414662
TI - Weil's Disease from a Local New Orleans Bar.
AB - INTRODUCTION: Leptospirosis is a zoonotic infection that typically presents with
fever, myalgias, nausea, and vomiting after contact with contaminated waters or
infected animals (typically rodents); and their excrements. Conditions favorable
to the transmission of leptospirosis are common in LA and, without treatment,
leptospirosis can lead to both liver and renal failure, meningitis, pulmonary
hemorrhage and ultimately death. CASE: A 56 year old woman with no past medical
history presented to the Emergency Department with weakness, myalgias, jaundice
and decreased urine output for one week. On arrival, she appeared septic with a
heart rate of 130 and fever. Her exam was significant for significant jaundice
and diffuse abdominal pain. Laboratory studies were notable for WBC 14,
hemoglobin of 12 and platelet count of 63. Creatinine was 8.5mg/dL with a blood
urea nitrogen of 96mg/dl. Total bilirubin was 19.4mg/dL and direct bilirubin was
13.7mg/dL. AST/ALT were 69/38 U/L, respectively and the alkaline phosphate was
160U/L. The patient was admitted to the hospital medicine wards for sepsis and
multi-organ failure. She was started on broad spectrum antibiotics but her
clinical condition continued to worsen with progressive decline in her hemoglobin
and thrombocytopenia and worsening liver failure. She quickly became anuric
necessitating dialysis and developed respiratory distress with bilateral
pulmonary infiltrates and hemoptysis. Additional history was obtained from her
employer that she works at a local New Orleans bar and had been cleaning out rats
from the kitchen. Leptospirosis antibody was sent, which returned as positive.
Her antibiotics were de-escalated to IV Ceftriaxone. She made a slow recovery
over the next two-week period. DISCUSSION: Since 1987, there has been an average
of 3 cases of Leptospirosis diagnosed per year, most of which have been from
southeast LA. This case illustrates the importance of considering the diagnosis
of Leptospirosis and Weil's Disease in patients in the southeast region of LA who
present with multi-organ failure. In addition, our patient's occupational
exposure was key to her diagnosis which emphasizes the importance of a detailed
history in clinical decision making and patient outcomes.
PMID- 28414663
TI - Not Another ACS Rule Out.
AB - CASE: A 50 year old African-American woman with diabetes, hypertension, and
hyperlipidemia presented with progressively worsening retro-sternal chest pain,
exacerbated by activity and relieved by rest. She also endorsed a thirty-pound
unintentional weight loss, and dysphagia. She was dysarthric with left-sided
Bell's Palsy and a palpable left axillary lymph node. She had been evaluated at
several hospitals in the previous months for similar typical chest pain. Her
troponin values were normal, and an EKG showed T-wave inversions in leads I and
aVL. On echocardiography, her ejection fraction was 45 percent with anterolateral
hypokinesis. She was treated for NSTEMI, and an angiogram showed 95 percent
stenosis of the right coronary artery. A modified barium swallow study revealed
weakened swallowing with aspiration of thin liquids. An MRI Brain demonstrated
scattered T2/ FLAIR hyper-intense foci in the subcortical white matter and focal
meningeal thickening. ANA, dsDNA, ANCA, and Lyme antibodies were all negative,
and a chest CT showed hilar lymphadenopathy. Cardiac MRI demonstrated scattered
foci of delayed enhancement in the mid-myocardium and sub-epicardium without
infarction. An endobronchial biopsy of hilar lymph nodes showed two small
epithelioid granulomas, consistent with Sarcoidosis. She was started on high-dose
corticosteroids with rapid improvement. A repeat modified barium swallow study
was normal and a repeat echocardiogram demonstrated recovered ejection fraction
of 55 percent with improved wall motion in the septum and apex. Additionally, her
left-sided Bell's Palsy and dysarthria improved after several days of therapy.
DISCUSSION: To our knowledge, this report is the third case of multi-organ
Sarcoidosis presenting as ACS. This case depicts the simultaneous presentation of
neurologic, pharyngeal, pulmonary, and cardiac Sarcoidosis. Myocardial
involvement in Sarcoidosis is rare and usually presents as conduction
abnormalities with arrhythmia rather than ACS. Though her symptoms were
consistent with Sarcoidosis, she had multiple risk factors for coronary
atherosclerosis including diabetes, hypertension, and hyperlipidemia. This case
highlights the importance of including Sarcoidosis in the differential diagnosis
for patients with recurrent typical chest pain of uncertain etiology.
PMID- 28414664
TI - Gonococcal Endocarditis: The Gift That Stops Giving! An Uncommon Presentation of
a Common Disease.
AB - INTRODUCTION: Gonorrhea is the 2nd most common sexually transmitted disease in
the US with 800,000 cases of gonorrhea each year. Disseminated gonorrhea
infection occurs in 0.5 percent - 3 percent of these patients and is more
frequent in woman younger than 40 years of age. CASE: A 36 year old woman with a
history of polysubstance abuse presented with 10 day history of feeling generally
unwell. At presentation, vitals were remarkable for tachycardia and hypotension.
Physical exam was remarkable for conjunctival pallor, bibasilar crackles, and
tachycardia with grade III/VI systolic murmur loudest over the 2nd inter-costal
space and loudest with expiration. No skin lesions were noted. Labs demonstrated
leukocytosis (WBC 20,200 with 84 percent neutrophils);, anemia (Hb 6.7);,
thrombocytosis (platelets 423 k/uL);, abnormal liver function tests (alkaline
phosphatase 239 IU, AST 151 IU ALT 71 IU, albumin 2.5g/dL);, PT/INR 17.1/1.5.
Troponin 0.42, BNP 823, D-dimer 619, and a urine drug screen that was positive
for benzodiazepines, opiates, barbiturates, amphetamine, and THC. Hep panel and
HIV were negative. Chest radiograph showed mild cardiomegaly and early
interstitial edema. The patient was placed on broad spectrum antibiotics and
given adequate fluid resuscitation and blood products. Blood cultures grew
Neisseria gonorrhoeae. 2D ECHO showed a large pedunculated/mobile echo density
adherent to the non-coronary and lefts cusps of the aortic valve. Proximal aortic
root and aorto-mitral continuity were thickened, consistent with aortitis and/or
abscess formation. Initial EKG on arrival showed junctional tachycardia which
progressed into complete heart block. Cardiology was consulted and a pacemaker
was placed emergently. However despite all aggressive measures the patient died
of cardiac complications. DISCUSSION: Endocarditis is a rare complication of
disseminated gonorrhea, occurring in only 1-2 percent of patients with
gonoccocemia. The aortic valve is most commonly affected. Valve replacement is
warranted in cases with severe dysfunction. Mortality remains around 19-20.
Neisseria gonorrhoeae endocarditis should be included in the differential
diagnosis in sexually active patients with endocarditis.
PMID- 28414665
TI - A Case of Early Neurosyphilis.
AB - INTRODUCTION: Neurosyphilis is an infection of the central nervous system by
Treponema pallidum, which can occur after the initial syphilis infection.
Although commonly associated with late stage disease, patients with early
neurosyphilis may present with acute syphilitic meningitis, meningovascular
syphilis, or uveitis. CASE: A 28 year old man with a past medical history of HIV
(CD4 364);, and recent diagnosis of uveitis presented to the Emergency Department
with a positive RPR result. His visual acuity had been gradually declining over
the past few months. He denied painless or painful ulcerating lesions on his
penis, or scrotum, difficulty concentrating, dermatitis on the soles/palms, or
difficulty with proprioception. Physical exam was notable for atrophic
hyperpigmented polycyclic, annular plaques and patches along the hairline as well
as several areas of confluent hyperpigmented polycyclic plaques and nodules on
the patient's face, back, left arm, and right posterior leg. Fundoscopic exam
revealed bilateral posterior uveitis and chorioretinitis. Evaluation of
cerebrospinal fluid revealed a lymphocytic pleocytosis with a positive VDRL and
FTA-ABS. Aqueous crystalline penicillin G was initiated for treatment of early
neurosyphilis. Within six hours of beginning the infusion, the patient had a
documented temperature of 101.8 degrees F, heart rate of 128 beats per minute,
blood pressure 142/84, with generalized malaise and headache. Fever and
tachycardia resolved over the next 12 hours, with weakness and headache resolving
within 1-2 days. His symptom complex was consistent with the Jarisch-Herxheimer
reaction. Histopathology of skin biopsy of the back showed perivascular
inflammation and rare spirochetes, consistent with secondary syphilis. The
patient completed 14 days of aqueous crystalline penicillin G and was discharged
after receiving the first of three benzathine penicillin injections. DISCUSSION:
The initial manifestations of syphilis in this patient were posterior uveitis and
pruritic skin plaques. His diagnosis should be appropriately classified as
secondary syphilis with concomitant symptomatic early neurosyphilis, requiring 14
days of aqueous crystalline penicillin G. This type of presentation is not
specific to immunocompromised populations and must be considered even in the
general population. Making the diagnosis of early neurosyphilis, regardless of
stage, is critical, as it necessitates a longer duration of treatment.
Furthermore, clinicians should be reminded of the profound immunologic reaction,
Jarisch-Herxheimer, which may occur when treating any treponemal disease.
PMID- 28414666
TI - Just a "Puff of Smoke".
AB - CASE: A 44 year old woman with a history of stroke s/p aneurysm clipping,
seizure, and substance abuse was brought to the hospital after a family member
received a call from her friend saying she was acting unusual and may have had a
seizure while hanging out on the street. At her baseline, she needed modest
assistance in daily activities after her CVA and conversed without issue. Her
mother died of a stroke. On exam the patient was afebrile, normotensive with mild
tachycardia to 110. The patient moved all her extremities but was lethargic,
agitated, responded to pain but would not follow commands and moaned nonsensical
speech. Labs were unrevealing with mild leukocytosis (WBC: 11.7 * 109/L);, normal
metabolic panel, ammonia, glucose, and a negative urine toxicology. Initial
computed tomography (CT); of her head demonstrated atrophy with large area of
encephalomalacia in Left middle cerebral artery (MCA); area. Repeat CT, 1 day
later showed edema and sulcal effacement in the right occipital, posterior,
temporal, and posterior parietal lobes with evolving infarct in right posterior
cerebral artery (PCA); and right MCA territories. CT angiogram showed occlusion
of the clinoid segments of both internal carotid arteries, consistent with
Moyamoya pattern of collateral flow. Neurosurgery was consulted and recommended
cerebral bypass. The patient was unable to consent for surgery and her closest
relative refused surgery. The patient received supportive therapy with minimal
improvements in word findings/ communication and no improvement in inability to
perform daily activities. She was accepted to inpatient stroke rehab upon
discharge. DISCUSSION: Moyamoya disease is a rare vascular condition which leads
to progressive stenosis of the internal carotid arteries through wall thickening
of the associated arteries which leads to progressive strokes and the development
of collateral vessels. Moyamoya is a Japanese term for a "puff of smoke" which
describes the appearance on imaging of the small collateral vessels that develop
around the progressively blocked arteries. There is a hereditary association and
our patient's mother likely had the disease as well. The prognosis is poor and
the disease will lead to a cognitive decline with associated CVAs. Treatment
includes cerebral revascularization or bypass. The case highlights the need for
early diagnosis, as our patient was too debilitated to make medical decisions for
treatment at the time of her diagnosis.
PMID- 28414667
TI - The Mysterious Case of Dyspnea.
AB - INTRODUCTION: Dehiscence of a mitral valve annuloplasty ring is a rare occurrence
that often manifests as mitral regurgitation and heart failure. We present a case
of mitral ring dehiscence which was initially unrecognized by standard 2
dimensional transthoracic echocardiography (2D TTE); and 2-dimensional
transesophageal echocardiography (2D TEE);. CASE: A 65-year-old woman was
referred to Cardiology clinic for evaluation of dyspnea. Her history included
tobacco abuse, atrial fibrillation status post pulmonary vein isolation,
nonischemic cardiomyopathy, and prior mitral valve repair with annuloplasty ring
for rheumatic valvular disease. She had been asymptomatic post-surgery. Physical
examination, cardiac rhythm and initial ischemic workup were unremarkable.
Pulmonary function tests revealed moderate emphysematous type obstructive lung
disease. A 2D TTE demonstrated moderate mitral regurgitation with normal left
ventricular function. In right heart catheterization, large v waves were noted
and 2D TEE also revealed severe mitral regurgitation. On 2D TEE, the mitral valve
annuloplasty ring was visible above the native anterior mitral valve leaflet.
Color Doppler flow estimated the effective regurgitation orifice area of 0.4cm2
using the proximal isovelocity surface area method and regurgitant volume of 58
cc, consistent with severe mitral regurgitation. A "floating mitral ring" and
dehiscence measuring 1 cm in diameter were seen on high resolution three
dimensional reconstruction resulting from the detachment of the ring from the
weakened posterior annulus. Based on these findings patient was referred to
cardiothoracic surgeon for re-do mitral valve surgery. DISCUSSION: This was a
perplexing case as the patient's dyspnea could be explained by many disease
processes including atrial fibrillation, mitral regurgitation and chronic
obstructive lung disease. The standard imaging modalities did not help us to
formulate a diagnosis. 3D TEE provided invaluable and unparalleled information of
mitral valve pathology. Annuloplasty ring dehiscence is a well described
complication of mitral valve repair and should always be considered in
symptomatic patients.
PMID- 28414668
TI - Autoimmune Diabetes Presented with Diabetic Ketoacidosis Induced by Immunotherapy
in an Adult with Melanoma.
AB - INTRODUCTION: Immunotherapy has been approved for treatment of melanoma.
Autoimmune endocrinopathies have been reported in trials involving immunotherapy
but autoimmune diabetes has not been definitively linked to them. Here we
describe a case of autoimmune diabetes presenting with DKA after receiving
combined immunotherapy with anti-CTLA4 and anti-PD1 monoclonal antibodies. CASE:
A 47year old gentleman with metastatic melanoma presented to our institution with
confusion, abdominal pain and decreased oral intake. The patient had a history of
diabetes on metformin which was discontinued two years prior. He was started on
Novilumab/Iplimumab for metastatic melanoma. He had received two cycles of
immunotherapy and treatment was initially well tolerated. However, eight days
after the second cycle the patient developed lethargy, confusion, vomiting and
abdominal pain. CT of the head was negative for intracranial abnormalities and
without evidence of brain metastasis. His laboratory results included: serum
sodium 126 mmol/L, potassium 6.7 mmol/L, BUN 55 mg/dL, creatinine 3.5,
bicarbonate 5 mmol/L, chloride 94 mmol/L, albumin 3.2 g/dL. Serum beta
hydroxybuterate was elevated (4.7 mmol/L, N: 0.0-0.5 mmol/L) and the calculated
anion gap was 43 mmol/L. Serum lipase elevated (535 u/L, N: 4-60 u/L). The
diagnosis of diabetic ketoacidosis was made and he was started on intravenous
fluids and insulin therapy. Given his history of metastatic melanoma, his DKA was
initially thought to be secondary to pancreatic metastasis especially considering
the elevated lipase level. A non-contrast CT of the abdomen showed no evidence of
pancreatic metastasis. Interestingly, further investigation identified high serum
titers of anti-glutamic acid decarboxylase (anti-GAD) antibodies (0.43 nmol/L, N:
less than 0.02 nmol/L), a low C-peptide level (0.2 ng/ml, N: 0.9-5.5 ng/ml),
supporting an autoimmune etiology of the diabetes. Other islet autoantibodies
were not elevated and his Hemoglobin A1C was 8.0 percent . DISCUSSION: There are
few case reports about diabetes and immunotherapy. Autoimmune mechanism was
suggested as the culprit, although not all cases reported with positive
antibodies. Moreover, it is unlikely that patient developed latent autoimmune
diabetes (LADA); and not related to immunotherapy due to the course of LADA is
quite more gradual and our patient presented with acute DKA few days post the
second cycle. Physicians and patients should be aware that autoimmune disorder
such as DKA may be a rare but important immunotherapy related adverse events.
PMID- 28414669
TI - A Case of Hepatosplentic T Cell Lymphoma - A Rare, Aggressive Tumor of the Young.
AB - INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL); is an unusual entity first
described in 1990 that predominantly affects middle-aged men and is classified by
WHO under peripheral T-cell lymphomas. We present a 26-year-old man with HSCTL
treated with a non-CHOP regimen. CASE: A 26 year old immigrant from Cameroon
without significant past medical history presented with abdominal discomfort that
was first noted 1 month prior at which time he was elbowed in abdomen during a
basketball game. His abdominal discomfort continued to gradually worsen and was
associated with nausea, vomiting, early satiety and decreased appetite. He
developed subjective fever, chills, night sweats, fatigue and epistaxis 3 days
prior to presentation. CBC with differential revealed WBC 8 x 103/ul, RBC 4.50 x
103/ul, Hemoglobin 12.9 mg/dl, Hematocrit 38.2 percent , Platelets 30 x 103/ul,
elevated monocytes and nRBC's. EBV serology was positive for VCA IgG and Nuclear
antigen Antibody IgG, indicating past infection. Abdominal CT revealed marked
hepatosplenomegaly with displacement of abdominal viscera. PET revealed
heterogeneously increased FDG uptake in liver and spleen. Bone marrow showed
increased cellularity, increased atypical lymphocytes with clustering, and
sinusoidal infiltration. Lymphoid cells mainly expressed CD2, CD3 and CD8. Cells
were negative for TdT, CD1a, and increase in Ki-67 expression. Bone marrow flow
cytometry revealed predominance of atypical gamma/delta T cells. Cytogenetics
revealed normal male karyotype. Based on imaging, bone marrow, and flow
cytometry, diagnosis of HSCTL was made. The patient was treated with 4 cycles of
Ifosfamide, Carboplatin and Etoposide (ICE);. PET showed complete resolution of
uptake in liver and spleen. Repeat bone marrow showed no residual disease. He
underwent splenectomy and pathology revealed no evidence of residual T-cell
lymphoma. The patient then underwent autologous SCT with BEAM (Carmustine
Etoposide-Cytarabine-Melphalan); conditioning. He remains in remission after
transplantation. DISCUSSION: Although HSTCL is rare, recognition is important as
it is aggressive, refractory to conventional therapies, and carries a uniformly
poor prognosis. Conventional therapy consists of CHOP (cyclophosphamide
doxorubicin-vincristine-prednisone); with or without autologous stem cell
transplantation (SCT);. A novel approach reported by Hoss et.al with a non-CHOP
induction therapy with or without splenectomy followed by autologous SCT may have
better outcomes as demonstrated with our case.
PMID- 28414670
TI - Diulafoy's Lesion - An Uncanny Etiology of Gastrointestinal Bleed.
AB - INTRODUCTION: Dieulafoy's lesion is a relatively rare, but potentially life
threatening, condition. It accounts for 1-2 percent of acute gastrointestinal
(GI); bleeding. CASE: A 99-year-old woman was initially admitted due to left
lower extremity cellulitis related to chronic venous stasis ulcer and was
receiving broad-spectrum IV antibiotics. Upon admission to the medical floor, she
had an episode of hematemesis and multiple bowel movements with black-tarry
stools. The patient denied chronic non-steroidal anti-inflammatory drug use. Her
past medical history was significant for dyslipidemia and remote history of colon
cancer status post colon resection. Home medications included atorvastatin 20 mg
and aspirin 81 mg. Digital rectal exam demonstrated melenic stool in the rectal
vault. Hemoglobin and hematocrit on admission were noted to be 12.1 g/dl and 40.7
percent respectively which dropped to 8.1 g/dl and 28.3 percent following her GI
bleed. A rise on BUN was also noted from 14 mg/dl to 34 mg/dl. Platelets and INR
were normal. She received fluid resuscitation with 2 liters of crystalloid and a
total of 2 units of pack red blood cells. Emergent EGD revealed a protruding and
oozing vessel surrounded by normal gastric mucosa located at the greater
curvature of the stomach body. The lesion was covered by a prominent fresh clot,
which was cleared. Endoscopic hemostasis was achieved with a combination of
epinephrine injection followed by BI-CAP electrocautery. The patient had an
uncomplicated post-operative course and hemoglobin remained stable. DISCUSSION:
Given this patient's clinical presentation, an upper GI bleed was suspected.
Based on the patient's advanced age and history of previous history of colon
cancer, the initial differential diagnosis included peptic ulcer disease versus a
GI malignancy. However, her EGD findings were consistent with a Dieulafoy's
lesion. Dieulafoy's lesions are twice as common in men as compared to women.
These lesions can occur in any age group are diagnosed more frequently in the
elderly population. Dieulafoy's lesions should be included in the differential
diagnosis of obscure GI bleeding in all age groups.
PMID- 28414671
TI - Three's a Crowd - An Extremely Rare Case of Cor Triatriatum Dexter.
AB - INTRODUCTION: Cor triatriatum is a congenital cardiac anomaly in which the left
(sinister) or right (dexter) atrium is divided into two compartments by residual
embryonic tissue, resulting in a tri-atrial heart. As cor triatriatum dextrum can
present clinically in various ways and have multiple associated cardiac
anomalies, this report attempts to contribute to what is known about this
exceedingly rare disorder. CASE: A 40 year old Hispanic man with a medical
history of gastritis presented with complaints of palpitations, dizziness and
bilateral lower extremity edema. He was found to have atrial fibrillation and new
onset heart failure. The patient was admitted for rate control and further
evaluation, which revealed several cardiac anomalies. Initial 2D echocardiography
demonstrated severe right atrial enlargement, right ventricular hypertrophy and
an engorged coronary sinus, which prompted further assessment of the patient's
cardiovascular anatomy. Transesophageal echocardiography (TEE) revealed a
severely enlarged, septated right atrium with a possible unroofed coronary sinus
and a small patent foramen ovale (PFO). Left- and right-heart catheterization
established a coronary-cameral fistula between the right coronary artery (RCA)
and right atrium, as well as left-to-right shunt. The patient improved clinically
with conservative management including diet modification, furosemide and digoxin
for fluid and rate control, and was referred to cardiothoracic surgery for
further evaluation. DISCUSSION: Cor triatriatum dextrum is an extremely rare
cardiac condition: In high-volume echocardiographic laboratories, prevalence is
less than 0.01 percent. This case highlights the association between cor
triatriatum and other congenital cardiac anomalies, including persistent left
superior vena cava with an unroofed coronary sinus, PFO and left-to-right shunt;
all of which were found in this patient. While cases of cor-triatriatum sinistrum
often require correction in infancy (due to left sided heart failure, pulmonary
edema and cyanosis), cor-triatriatum dextrum is sometimes diagnosed in adulthood
due to the lack of left heart and pulmonary involvement.
PMID- 28414672
TI - A Strong and Fortuitous Case of Dyspnea.
AB - CASE: A 48 year-old man with no past medical history was sent to our emergency
department (ED); from a primary care clinic for hypertensive urgency of 200/130.
The man reported an intermittent non-productive cough of approximately one year's
duration and worsening dyspnea on exertion and orthopnea over the last month with
lower extremity swelling. Of note, he emigrated from Honduras twenty years ago.
Blood pressure normalized with administration of Lasix in the ED. Physical exam
revealed rales in lung bases bilaterally, jugular venous distension, lower
extremity pitting edema with serpiginous patches of erythema and excoriation, and
a cardiac gallop. Labs showed peripheral eosinophilia, thrombocytopenia, elevated
creatinine, hyperbilirubinemia, hyperglycemia, and mild transaminitis.
Transthoracic echocardiogram revealed a dilated left ventricle with global
hypokinesis and severely depressed systolic function with an ejection fraction
less than 15 percent . The patient was diuresed, and subsequent left and right
heart catheterizations were normal. CT chest showed a small nodule in the right
upper lobe. Tests for Coccidiosis, Trypanosoma cruzi, and Mycobacterium
tuberculosis were negative; however the acid fast bacilli culture grew
Mycobacterium fortuitum. A Strongyloides stercoralis antibody test was positive,
and the patient was treated with two doses of oral ivermectin with one dose of
intravenous ceftriaxone, and discharged. Two months later, his eosinophilia
resolved, but he remained symptomatic with productive cough and weight loss, and
was started on an outpatient course of oral ciprofloxacin and trimethoprim
sulfamethozole for M. fortuitum. DISSCUSION: Strongyloides-infected patients may
carry the parasite for years without prominent symptoms. Endemic throughout South
America, Strongyloides persists in its hosts through a lifecycle of
autoinfection, which, over time, increases parasite burden and can lead to a
hyperinfection syndrome whereby filiariform larvae penetrate organ tissue, most
commonly: heart, central nervous system, lungs and liver. We suspect chronic
eosinophilia and disseminated filiaria to be the etiology of the non-ischemic
dilated cardiomyopathy in this patient. Standard treatment of strongyloidiasis is
ivermectin, however, mortality owing to transient bacteremia in the setting of
hyperinfection syndrome is high. Therefore, bacteremia prophylaxis with gram
negative rod coverage should be considered before antiparasitic agent initiation.
PMID- 28414673
TI - Purulent Pericarditis Due to an Infected Pacemaker Lead.
AB - INTRODUCTION: Intravenous drug users have a substantially increased risk of
infective endocarditis, especially in the setting of implanted cardiac devices.
Purulent pericarditis is a rare occurrence that can occur iatrogenically or
through direct or hematogenous spread. CASE DESCRIPTION: A 75 year old man with a
past medical history significant for hepatitis C, IV drug abuse, and sick sinus
syndrome status post pacemaker was brought in by EMS with a chief complaint of
diaphoresis and chest pain. Initial EKG revealed atrial fibrillation with ST
elevations in multiple leads. The patient was taken urgently to the cardiac
catheterization lab due to concern for STEMI. Left heart catheterization revealed
nonobstructive CAD; bedside echo was significant for a pericardial effusion and a
pacemaker lead vegetation. CT of the chest revealed extension of the ventricular
pacemaker lead through the anterior right ventricular wall and pericardium and
into the pleural cavity. Cardiothoracic surgery performed a pacemaker removal as
well as pericardial window due to early tamponade; approximately 900 mL of
purulent fluid was drained from the pericardial space. The patient was septic
with initial blood cultures growing MSSA. He was also found to have multiple
other foci of infection including a left-sided pleural effusion and a perihepatic
fluid collection, both of which were drained and also grew out MSSA. The patient
initially improved on antibiotics after his pacemaker removal and drainage of the
infected fluid collections. However, several days after the pacemaker removal he
gradually became more bradycardic; due to his multiple comorbidities and active
infection, he was not a candidate for a replacement implanted pacemaker. He
became profoundly bradycardic and hypotensive overnight and died despite the use
of multiple pressors to maintain his blood pressure as well as transcutaneous
pacing to maintain his heart rate. DISCUSSION: Purulent pericarditis has become a
relatively uncommon occurrence since the development of effective antibiotics.
This case illustrates a rare example of purulent pericarditis and cardiac
tamponade secondary to the extension of an infected pacemaker wire through the
pericardium and into the thoracic cavity. The presence of multiple other infected
fluid collections in this case also illustrates the need to thoroughly assess for
secondary foci of infection in cases of bacterial endocarditis.
PMID- 28414674
TI - A Clot (Possibly); Due to Loss of TNF-alpha Supression.
AB - INTRODUCTION: Inflammation and venous thrombosis enjoy a close Relationship. We
present a patient who had multiple DVTs following the discontinuation of anti-
TNF-alpha therapy. CASE: A 34 year old African American female with a history of
multiple DVT's, miscarriages, and reported Crohn's disease presented with
shortness of breath. In the Emergency Department, CTA showed bilateral pulmonary
emboli. The patient had been off adalimumab for one year and reported abdominal
pain with 6-7 non-bloody bowel movements daily. She had been prescribed lovenox
for her unprovoked DVTs yet reported missing several doses prior to admission.
Following admission, she developed severe abdominal pain prompting an emergent CT
angiogram and she then developed a pulseless painful left lower extremity. CT
revealed a partially occlusive thrombus in the infra-renal abdominal aorta,
proximal left common iliac artery, and right renal artery with subsequent right
renal infarction. Following emergent vascular surgery to restore blood flow to
the left lower extremity, the patient received four days of plasma exchange and
high dose steroids for potential catastrophic antiphospholipid syndrome. Serology
for APLA was negative. The patient was discharged with lifelong anticoagulation.
DISCUSSION: The endothelial surface is a complex organ that works in concert with
the surrounding environment. Inflammation and thrombus formation is closely
associated. TNF-alpha can increase the expression of adhesion molecules,
specifically, tissue factor, on the surface endothelial cells and promote
thrombosis. Suppression of TNF-alpha expression by low molecular weight heparin
has been shown to inhibit the inflammatory cascade and reduce thrombus formation
in animal models. Clinical data is less clear. Interruption of TNF blockers has
been shown to increase the risk of DVT in patients with rheumatoid arthritis
undergoing orthopedic surgery. For patients with Bechet's syndrome, anti-TNF
agents appear help treat patients with pulmonary artery thrombosis. Further
review of anti-TNF-alpha therapy in our general medicine patient population may
disclose additional risks associated with discontinuation of these medications.
PMID- 28414675
TI - Case Report of Sarcoidosis as a Great Mimicker in Various Populations.
AB - INTRODUCTION: The prevalence of sarcoidosis varies as much as 1-40 cases per
100,000 depending on region and population. Sarcoid typically occurs in people
younger than 50 years old, with a peak incidence with ages between 20 and 40
years old. African Americans are 3 times more likely to develop sarcoidosis than
Caucasian Americans, and woman are more likely than men to develop sarcoidosis in
any ethnic group; nonetheless, it remains a valid differential across any
population. CASE: A 32 year old Hispanic man presented to the Emergency
Department with night sweats, fatigue, and 35 pound unintentional weight loss
over the last several weeks. He also reported a sore throat, occasional cough w/
yellowish sputum, and new onset dyspnea with exertion. He moved from Mexico to
the U.S. 20 years prior and last visited the country 7 yrs ago. He never smoked
and denied any TB exposure. His vitals at admit demonstrated tachycardia (pulse
108); and temperature of 99.4 ?F. He had coarse bilateral breath sounds on exam.
Serum chemistries were unremarkable. Chest radiograph demonstrated perihilar
fullness. Chest CT revealed enlarged mediastinal and perihilar LAD and airspace
consolidation in right middle and lower lobes bilaterally. The patient was
admitted to a negative pressure room w/ airborne precautions and RIPE therapy was
initiated. PPD and AFB's were negative. He underwent bronchoscopy and was
discharged on RIPE. Lung biopsy showed non-caseating granulomas. RIPE therapy was
stopped, and he was referred to ophthalmology to rule out uveitis. Cultures from
the procedure were negative for fungal growth, and he was started on prednisone
40 mg daily with taper 6 weeks later as his weight returned, night sweats
subsided, and dyspnea on exertion improved. DISCUSSION: Sarcoidosis should be
considered as a diagnosis in any gender of any racial or ethnic group. Sarcoid is
a great mimicker of many serious illnesses including malignancies such as
lymphomas, TB and atypical mycoplasma, fungal infections, and other granulomatous
diseases, and other autoimmune disorders such a hypersensitivity pneumonitis.
Diagnosis requires patient investigation and careful analysis of these
differentials.
PMID- 28414676
TI - Pheochromocytoma of the Organ Zuckerkandl.
AB - INTRODUCTION: Pheochromocytomas (PCCs);, or intra-adrenal paragangliomas (PGLs);,
are neuroendocrine tumors arising within the adrenal medulla. Extra-adrenal
paragangliomas may arise in the sympathetic or parasympathetic paraganglia and
more rarely in other organs. One of the most common extra-adrenal sites is in the
organ of Zuckerkandl, a collection of chromaffin cells near the origin of the
inferior mesenteric artery or near the aortic bifurcation. The following is a
case of a patient with resistant hypertension secondary to an extra-adrenal
paraganglioma in the organ of Zuckerkandl. CASE: The patient is a 43 year old man
with a history of depression, type 2 diabetes mellitus, and hypertension who was
sent to the emergency department by his primary care physician for severely
elevated blood pressures. Patient also had diaphoresis, tachycardia, and a new,
fine tremor of his left hand. Upon presentation, the patient's blood pressure was
260/120 mmHg with a heart rate of 140 beats per minute. Plasma fractionated
metanephrines sent on admission revealed significantly elevated levels of total
plasma metanephrines (2558 pg/mL);, free metanephrine (74 pg/ml); and free
normetanephrine (2484pg/mL);. An I-123 metaiodobenzylguanidine (MIBG); scan
showed abnormal uptake in the lower abdomen at the level of the aortic
bifurcation. Patient was started on alpha-blockade, with subsequent addition of a
beta-blocker prior to surgery. Patient underwent surgical removal of the tumor
with pathology consistent with a paraganglioma. DISCUSSION: Pheochromocytomas and
paragangliomas are responsible for approximately 0.5 percent of cases of
secondary hypertension. Many different biochemical markers have been used to aid
in the diagnosis of PCC/PGL including plasma catecholamines, plasma
metanephrines, urine fractionated metanephrines, urine catecholamines, total
metanephrines and vanillymandellic acid. Definitive management of a PCC and PGL
involves surgical removal of the tumor. Finally, there should be a discussion
with each patient to determine if he or she should undergo genetic testing, as
studies show that approximately 25 percent of catecholamine producing PCCs and
PGLs are due to heritable genetic mutations.
PMID- 28414677
TI - A Rare Case of Tropical Pyomysitis Acquired on Vacation in a Healthy Male.
AB - INTRODUCTION: Pyomyositis has traditionally been considered a tropical disease.
Increasing prevalence has been observed in more northern climates, especially
with HIV, immunosuppression, and IV drug abuse as predisposing factors.
Pyomyositis has the tendency to mimic other conditions, such as muscle contusion,
necrotizing fasciitis, or septic arthritis. The rarity of this disease and non
specificity of its symptoms often lead to delay in appropriate diagnosis and
treatment. CASE: 24-year-old man, seen 2 days prior in orthopedics clinic and the
Emergency Department for persistent gluteal pain thought to be due to right-sided
sciatica, was admitted following worsening pain, diffuse generalized weakness
with polyarthralgias and myalgias These symptoms were associated with night
sweats, shaking chills, and difficulty walking. Prior to onset of symptoms, the
patient vacationed in Cayman Islands and experienced a stingray bite on his right
hand as well as numerous cuts on rocks in stagnant waters. He was febrile with
WBC count of 18.7 K/ MUL and was found to have methicillin-sensitive
Staphylococcus aureus (MSSA); bacteremia. Magnetic resonance imaging (MRI); of
his lumbar spine on admission was unremarkable. Repeat MRI 4 days later showed
extensive inflammation within musculature with multiple abscesses around right
sciatic foramen and septic arthritis of the sacroiliac joint. The patient was
subsequently diagnosed with MSSA septic polyarthritis and required several
orthopedic procedures. Infectious and oncologic work up was unremarkable.
Transesophageal echocardiogram showed 0.3 cm x 0.5 cm aortic valve vegetation,
which was managed medically. Repeat MRI 11 days after initiation of appropriate
antibiotics and surgeries showed improvement in muscular edema. Based on the MSSA
susceptibilities, the patient was treated with 6 weeks of intravenous cefazolin
and 2 weeks of oral cephalexin thereafter. DISCUSSION: Awareness of tropical
pyomyositis in colder climates remains scarce, although cases have been reported
in immunosuppressed patients. However, in healthy patients, accurate history of
travel and trauma is important in evaluation for predisposing factors for
pyomyositis. Early antibiotic and appropriate surgical interventions are
imperative for management of this disease in order to prevent systemic toxicity,
dissemination of infection, and long-term debility.
PMID- 28414678
TI - What the Eyes Don't See, the Heart Does Grieve Over.
AB - INTRODUCTION: A 71 year old Peruvian woman presented with blurry vision and
bilateral eye pain and had evidence of bilateral endophthalmitis on eye
examination. Her past medical history was notable for multiple abdominal
surgeries within the preceding months, including an incarcerated inguinal hernia
repair which required an ileostomy placement, and cholecystitis requiring
cholecystostomy tube placement. Over her multiple long hospitalizations, she
developed bacteremia and fungemia on several occasions, with organisms including
Enterobacter cloacae, Klebsiella pneumoniae, Bacteroides fragilis, Pseudomonas
aeruginosa, Enterococcus faecium, and Candida albicans. On exam, she was febrile
and tachycardic. She had bilateral conjunctival injection, hypopyon, and severely
decreased visual acuity. She also had a III/VI harsh holosystolic murmur at the
apex. Her lungs were clear to auscultation. Transesophageal echocardiogram
revealed severe mitral regurgitation and a 16 x 15 mm mitral valve vegetation and
a perforated aneurysmal posterior mitral valve leaflet. The patient underwent
bilateral vitrectomy and was treated with flucytosine and ambisome. Blood and
vitreous humor cultures were obtained, but remained negative, likely due to being
drawn after the patient had been empirically treated with antifungals and
antibiotics. She continued to spike fevers and developed heart failure, but
refused valve replacement surgery as she wished to return to her home country.
DISCUSSION: A systemic source of infection should be sought in the presence of
bilateral endophthalmitis. In our case, we suspected seeding from endocarditis or
an intra-abdominal infection, given the patient history of multiple complicated
abdominal surgeries and recurrent bacteremia and candidemia. Based on the
vegetation's large size and bilateral endophthalmitis, we believed Candida was
the most likely culprit. Additionally, eye lesions observed during surgery
appeared consistent with fungal endophthalmitis. Candida is a rare but very
morbid cause of infective endocarditis. Arterial embolization and metastatic
infections such as endophthalmitis are more frequent in candidal endocarditis,
likely due to the generally larger vegetation size. Valve replacement should be
strongly considered regardless of other factors, as some studies have shown a
mortality benefit for antifungals and surgery compared to antifungals alone. In
cases in which valve replacement is not feasible, the patient should be kept on
lifelong suppressive antifungal therapy.
PMID- 28414679
TI - Misses Opportunity: TOF Diagnoses in 4th Decade of Life.
AB - CASE: A 40 year old woman with a history of HIV, congestive heart failure
secondary to an unknown congenital heart defect, and hypertension presented to
our emergency department with worsening edema. On room air, oxygen saturation was
55 percent . On 5L of oxygen via nasal cannula, oxygen saturation was 88 percent
. Physical examination was notable for central cyanosis, facial and lid edema, a
II/VI holosystolic murmur across right chest radiating to entire right back
hemithorax, decreased breath sounds at bases with pulmonary crackles, clubbing of
fingers and edema of bilateral lower extremities. The patient related lifelong
knowledge of a congenital heart defect, but had not been seen by a cardiologist
as an adult. She was asymptomatic, yet sedentary until one year ago when she had
the first of multiple hospitalizations for acute decompensated heart failure. A
chest x-ray showed massive cardiomegaly with right-sided calcified aortic arch
and patchy bilateral infiltrates. Transthoracic echocardiogram revealed severe
right ventricular hypertrophy, ventricular septal defect, overriding aorta, and
ejection fraction of 50 percent , consistent with unrepaired ToF. We utilized
multimodality imaging techniques including CT angiography and Cardiac MRI which
further defined her cardiac anatomy. Findings were consistent with unrepaired ToF
with pulmonary atresia. The pulmonary arteries arose directly from the aorta in a
confluent fashion via a large patent ductus arteriosus, major aortopulmonary
collateral artery. The arterialized pulmonary arteries were aneurysmal with
dissection and mural thrombus formation. DISCUSSION: This case illustrates how a
patient with a rare presentation of unrepaired ToF with pulmonary atresia can go
undiagnosed into adulthood. Early recognition utilizing a multimodality imaging
approach can lead to proper diagnosing and hopeful surgical repair which can
provide considerable improvement in functional status and long-term survival.
PMID- 28414680
TI - A Rare Cause of Abdominal Pain.
AB - CASE: A 54 year old woman with hypothyroidism presented with right flank pain
that began acutely one week prior to presentation. She was told initially she had
a urinary tract infection and treatment resulted in mild symptomatic improvement.
The pain returned and she presented to another Emergency Department (ED); and was
told the pain was due to constipation. She returned to the ED the next day when
her pain worsened and her labs were notable for WBC of 19,000/uL, BUN/Cr of
28/0.75 mg/dL, AST of 31 U/L, ALT of 92 U/L and total bilirubin of 0.6 mg/dL. RUQ
ultrasound was notable for dilation of the common bile duct. Given concern for
choledocholithiasis, she was started on cefepime and metronidazole. MRCP
demonstrated a distended gallbladder without stones and a small amount of
pericholecystic fluid. Also noted were two areas of increased signal in the right
kidney, concerning for neoplasia or infarction. Contrasted abdominal Computed
tomography showed a moderate size area of hypodensity, consistent with renal
infarct. Workup for embolic source of the infarction was unrevealing. Renal
artery angiogram demonstrated a spontaneous dissection of the superior branch of
the right renal artery. PCI was not performed due to risk of jeopardizing the
other vessels and so she was managed medically with rivaroxaban along with
hydrochlorothiazide and metoprolol succinate to keep her systolic blood pressure
below 140 mmHg. The morning after the procedure, the patient told the treatment
team that her grandson liked to jump from a height and she would catch him on her
right side. This was felt to be a likely etiology of her spontaneous dissection.
At the time of discharge, her pain was improved and repeat angiogram performed
eight weeks later noted healing of the dissection. DISCUSSION: Spontaneous renal
artery dissection is a rare cause of abdominal pain and often presents a
diagnostic and therapeutic challenge. This case highlights the importance of
considering alternate etiologies of localized abdominal pain when other common
pathologies have been excluded.
PMID- 28414681
TI - What Can Erode Through Lungs, Bone and Skin?
AB - CASE: A 51 year old African American Man without significant past history
presented with three weeks of persistent cough productive of copious yellow
sputum. He denied fevers, chills, hemoptysis, dyspnea, weight or appetite
changes, sick contacts, recent travel. On physical examination, the patient was
afebrile and appeared comfortable. He had decreased air entry of the left lower
lobe with dullness to percussion. A 5x3 cm fluctuant mass was incidentally found
on the left anterior chest wall at the level of the 11th rib with yellow
expressible exudate at which time the patient reported a minor trauma sustained 3
weeks prior. WBC count was 17,300/mcL. CT chest identified a peripherally
enhancing fluid-attenuation structure in the left lower lung measuring 11.8 cm x
11.3 cm x 9.6 cm. The collection appeared to be tracking out from the pleural
space to the exterior skin that corresponded to the site of the chest wall
swelling. There was also a focal lytic lesion of the adjacent ribs. He was
empirically started on Vancomycin, clindamycin and piperacillin-tazobactam.
CTguided aspiration failed because the material was too viscous to be aspirated;
a chest tube drained copious yellow exudate. Blood cultures and respiratory
cultures were negative. Gram stain of the purulent material demonstrated clusters
of branching gram positive rods. Pathology showed necrotic debris with clusters
of filamentous gram negative organism. Acid fast and Kinyoun stains were
negative. He was started on empiric Penicillin G for empyema necessitans with a
presumed etiology of actinomyces. Due to development of hypersensitivity drug
eruption from PCN, intravenous doxycycline was started for total of 14 days
followed by 6 months of oral therapy. Imaging four weeks after treatment showed
significant reduction in size of the lesion. Culture confirmed Actinomyces
israelii. DISCUSSION: Actinomyces are anaerobic gram positive commensals of the
oral cavity notorious to breach though tissue planes. Thoracic manifestations are
varied and can mimic malignancy. Astute microbiology and pathology tests are
necessary to make an early diagnosis and prevent invasive surgery as the organism
is a slow growing anaerobic bacteria. Excellent clinical and radiologic response
were noted in our case following treatment with chest wall drainage and
antibiotics thus avoiding invasive thoracic surgery.
PMID- 28414682
TI - A Left Main Coronary Artery Thrombus Presenting as a Non St Elevation MI.
AB - INTRODUCTION: Left main coronary artery (LMCA); thrombus with an acute myocardial
infarction identified with coronary angiography is a clinically rare condition
with an extremely high mortality rate. We present a case of LMCA thrombus that
presented as a non-ST elevation myocardial infarction (NSTEMI);. CASE: A 45-year
old woman with a history of tobacco use and hyperlipidemia presented with a
complaint of 10/10 "hard pain" across her chest radiating to her left shoulder
and breast which woke her from sleep. The pain was constant and severe, with no
alleviation with rest. She had not experienced anything like this before. Workup
revealed an upward trending troponin (1.9?8.98?9.79);, and an EKG with some
tachycardia but no ST elevation or T wave changes. Her CBC, CMP and coagulation
studies were unremarkable. A toxicology screen was positive for opiates and
benzodiazepines, medications she was on for pain and anxiety respectively. ACS
protocol was started with DAPT, LMWH, Statin, ACEi, and Beta-blocker. An
angiogram revealed a large thrombus in the LM coronary artery extending into the
aorta with concomitant 99 percent stenosis of distal LAD. 2D Echo w/ bubble
contrast was significant for PFO, akinetic apical inferior and anterior wall. The
mid antero-septum and apical lateral wall were hypokinetic. Interventional
Cardiology and CTS recommended conservative management with medical optimization
(Continue DAPT, heparin);, watchful waiting for the thrombus to resorb.
DISCUSSION: Left main coronary artery thrombosis (LMCAT); identified during
coronary angiography is a rare and challenging condition. It is a life
threatening condition with an approximate incidence rate of 0.8 percent . It is
thought to be secondary to plaque rupture with subsequent thrombus formation that
is associated with persistent hypercoagulable state, cocaine induced plaque
rupture or coronary vasospasm, post-partum state and embolization of intra
cardiac masses. The patient presentation can vary from sudden cardiac death to
STEMI, NSTEMI, unstable angina and cardiogenic shock. Standardized therapy has
not been developed due to the small number of reported cases.
PMID- 28414684
TI - Who Shot the Cannonballs? Extensive Lung Metastases in a 39 Year Old Man.
AB - CASE: A 39 year-old man presented to the emergency department complaining of a
cough of 2 months in duration. He also complained of weight loss of 20 pounds in
two months and night sweats over the same period. An x-ray of the chest was
performed and revealed innumerable lung nodules and masses. Computed tomography
of the chest and abdomen were subsequently performed which confirmed the masses,
but imaging did not reveal an obvious primary source. A testicular exam was
performed but no obvious abnormalities were noted. Because of his age as well as
the appearance of the lesions, a testicular ultrasound was then performed. The
ultrasound found evidence of a 1.5 cm hypoechoic mass on the right testicle with
dystrophic calcification in the interpolar region. Urology performed a right
radical inguinal orchiectomy. Pathology demonstrated a malignant mixed germ cell
tumor with seminoma and yolk sac components being prominent. He underwent four
cycles of etoposide, ifosfamide, and cisplatin. His last positron emission
tomography scan did not demonstrate active disease. DISCUSSION: Each year about
8700 men are diagnosed with testicular cancer. 75 percent of these occur between
the ages of 20 to 44, and the median age of diagnosis is 33. Testicular cancer
should be suspected when a young male presents with metastatic disease such as in
this case. In this patient, the genital exam was normal due to the small size of
the testicular mass, but he had significant metastatic lesions. When cannonball
metastases are seen on imaging, germ cell tumors and renal cell carcinoma should
be high in the differential diagnosis.
PMID- 28414683
TI - Recurrent Hypertriglyceridemic Pancreatitis (HTGP); and the Use of Insulin Drip
as Treatment.
AB - INTRODUCTION: Chronic pancreatitis by definition is a recurrent episode of acute
pancreatitis and is commonly associated with alcoholism in the US. Another cause
of chronic pancreatitis is hypertriglyceridemia (HTGP);, occurring in 1-5 percent
of cases. The incidence of HTGP is higher in patients with diabetes and HIV,
usually requiring triglyceride levels > 1000 mg/dL. CASE: A 33 year old man with
uncontrolled type 1 diabetes and recurrent pancreatitis, first diagnosed 5 years
prior, presented as a transfer from an outside hospital for a recurrent episode
of HTGP. He reported recurrent pain episodes, requiring 6-9 hospitalizations
within the last year for pancreatitis. He reported poor compliance with his
insulin regiment at home. Other home medications included gemfibrozil,
lisinopril, niacin, and omega-3 fatty acid. On transfer, his glucose was 296,
triglyceride level was >3600, and A1C of 12.4. Transfer report lab work showed a
triglyceride level >7000 and a lipase of 600. The patient had severe, diffuse
abdominal tenderness on examination. He was diagnosed with pancreatitis secondary
to hypertriglyceridemia due to a lipoprotein metabolism disorder and long
standing uncontrolled DM1. An intensive insulin drip was started on this patient,
with goals of correcting his TG to less than 500 along with lowering his glucose.
After 13 days, mostly on insulin drip, his TG decreased to 995 and pain was
controlled, eventually tolerating a diabetic diet. He was encouraged to modify
his diet and take his medications as directed at discharge. DISCUSSION: The
relationship between hypertriglyceridemia and pancreatitis is poorly understood.
In HTGP, a decrease in triglyceride concentration is a management priority. Rapid
triglyceride concentration lowering is managed by insulin or plasmapheresis. As
HTGP often presents in patient with uncontrolled diabetes, insulin is frequently
used as treatment to lower both blood glucose and triglycerides; insulin
decreases serum triglyceride levels by enhancing lipoprotein lipase activity and
inhibiting hormone sensitive lipase, accelerating metabolism and decreasing
adipocyte breakdown. Patients should be educated on the importance of compliance
with drug therapy and lifestyle modifications.
PMID- 28414685
TI - Association of State-Mandated Abstinence-only Sexuality Education with Rates of
Adolescent HIV Infection and Teenage Pregnancy.
AB - INTRODUCTION: Abstinence-only sexuality education (AOSE); is required in the
public school systems of many states, raising public health concerns and
perpetuating health disparities through school systems. This study aimed to
determine the correlations between state-mandated AOSE and the rates of
adolescent HIV and teen pregnancy. METHODS: Using publicly available data on all
50 United States' laws and policies on AOSE, states were ranked according to
their level of abstinence emphasis on sexuality education (Level 0 - Level 3);.
We calculated the relative proportion of Black students in public schools and the
proportion of families below the federal poverty line then ranked them by state.
We compared the states' ranks to the incidence of adolescent HIV and teen
pregnancy in those states to identify associations between variables. RESULTS:
The majority of states (~44 percent ); have legally mandated AOSE policies (Level
3); and adolescent HIV and teen pregnancy rates were highest in these Level 3
states. There were significant, positive correlations between HIV incidence rates
of 13-19 year olds, HIV rates of 20-24 year olds, teen pregnancy rates, and AOSE
level, with the proportion of the population that lives below the federal poverty
level, and whether they attended schools that had a greater than 50 percent of an
African American population. DISCUSSION: These data show a clear association
between state sexuality education policies and adolescent HIV and teen pregnancy
rates not previously demonstrated. Our data further show that states that have
higher proportions of at-risk populations, with higher adolescent HIV and teen
pregnancy rates, are more likely to also have restrictive AOSE policies. These
populations may be more likely to attend public schools where AOSE is taught,
increasing their risk for HIV and teen pregnancy. The World Health Organization
considers fact-based Comprehensive Sexuality Education a human right, and the
authors believe it is past time to end harmful, discriminatory sexuality
education policies in US public schools.
PMID- 28414686
TI - Severe Sepsis and Septic Shock Cases Meeting Guidelines Among Patients in a
University Hospital Setting.
AB - BACKGROUND: A diagnosis of severe sepsis or septic shock has been shown to
significantly increase mortality rate independent of other factors. Research has
revealed all cause hospital case fatality rates have declined yet the percentage
of severe sepsis cases continues to increase and age-adjusted mortality rates
from severe sepsis and septic shock has significantly increased during the same
time period. Patients with severe sepsis demonstrate ongoing mortality rate
increases for up to 2 years following hospitalization when compared to aged
matched controls of nonseptic patients. International guidelines with mortality
benefit for the management of severe sepsis and septic shock have been
illustrated in the latest surviving sepsis campaign. OBJECTIVE: The objective of
this study was to increase the percentage of patients admitted to the hospital
with a diagnosis of severe sepsis or septic shock who met guidelines based on
surviving sepsis campaign. METHODOLOGY: A retrospective chart review was
conducted for patients admitted to UHC from January 2016 to present to identify
cases with a diagnosis of severe sepsis or septic shock, and whether they met
guidelines set forth by surviving sepsis campaign both before and after an
intervention program which included interviews with providers failing to meet
protocol, educational sessions on guidelines to meet protocol, resident led
quality improvement workshops to address barriers to meeting protocol, and
development of an EMR power plan to assist providers on meeting protocol.
RESULTS: 139 cases with a diagnosis, or meeting criteria for, severe sepsis or
septic shock were identified during the period of 1/1/2016-9/30/2016 with an
average of 43 percent of total cases which met guidelines. Trend analysis
revealed increased compliance following resident lead intervention program with
31 percent and 49 percent before and after intervention, respectively. ICU data
is currently being analyzed for meeting guidelines and have not been included in
current data. The most common reason for failing guidelines was failure to obtain
or repeat lactic acid on time (46 percent ); and failure to give timely
antibiotics (22 percent );. CONCLUSIONS: The percentage of patients admitted to
the hospital with a diagnosis of severe sepsis or septic shock at UHC meeting
guidelines set forth by surviving sepsis campaign has improved following resident
lead intervention program. Intervention strategies to further improve compliance
with guidelines with a goal >60 percent are currently being analyzed.
PMID- 28414687
TI - Disseminated Cryptococcal Disease with Diffuse Pulmonary Infiltrates in a Non-HIV
Host.
AB - INTRODUCTION: We present a case of disseminated Cryptococcus in a non-HIV host,
where the primary manifestation was pulmonary with diffuse pulmonary infiltrates.
This patient was on high dose corticosteroids for autoimmune hemolytic anemia.
CASE: A 79 year old Caucasian man with a history of autoimmune hemolytic anemia
on 100 mg of prednisone daily, coronary artery disease s/p bypass surgery,
ischemic cardiomyopathy, chronic obstructive pulmonary disease, sleep apnea,
chronic kidney disease, and history of bilateral pulmonary emboli presented to
Hematology/Oncology clinic with symptoms of productive cough, worsening shortness
of breath, hemoptysis. Anticoagulation had been stopped due to symptoms. The
patient was referred to the emergency department from clinic where a chest CT
demonstrated numerous calcified lymph nodes and diffuses grand glass opacities
worse on the right and new compared to imaging from 6 months prior. The patient
was placed on empiric antibiotics for treatment of pneumonia after blood and
sputum cultures were obtained. Initial blood cultures grew Cryptococcus
neoformans in both sets. CSF obtained by Lumbar puncture was negative for
Cryptococcal. Serum Cryptococcal antigen titer was 1:2560. Infectious disease was
consulted and the patient was started on induction therapy with liposomal
Amphotericin B, followed by Fluconazole consolidation therapy. Hematology/
Oncology reduced the patient's prednisone dose gradually but further
complications attributed to corticosteroids eventually necessitated the need to
transition to Rituximab therapy. Follow up imaging on return to pulmonary clinic
demonstrated marked improvement in the bilateral infiltrates. DISCUSSION: This
patient was unique in that he demonstrated disseminated Cryptococcus but lacked
neurologic complications, which is often how disseminated disease is clinically
suspected. Blood cultures resulted positive for Cryptococcus and appropriate
antifungal therapy was initiated before other sites were affected. The patient
was HIV negative and not a post-transplant patient but was on high dose chronic
prednisone for his AIHA, and therefore immunosuppressed. Opportunistic and
atypical infections should be considered in all immunosuppressed patients to aid
in earlier diagnosis and prevention of further dissemination of disease and
further complications.
PMID- 28414688
TI - ECG Of The Month: Mental Disturbance for 4 days.
AB - A family brought their 61-year-old mother to the emergency department because for
4 days she had been confused, incoherent, and somnolent. She also had dysphagia,
dysarthria, diplopia, and had fallen out of bed. She had been in the hospital 3
weeks earlier for atrial fibrillation and an exacerbation of congestive heart
failure. She also carried a diagnosis of chronic obstructive pulmonary disease
and used an albuterol inhaler. She was obese (BMI of 45); and had adult-onset
diabetes mellitus. She had a 43 pack-year history of cigarette smoking but had
recently quit. Soon after arriving in the emergency department, she had an ECG
(Figure);.
PMID- 28414690
TI - Injectable Biological Treatments for Osteoarthritis of the Knee.
PMID- 28414689
TI - Radiology Case Of The Month: Mental Disturbance for 4 days.
AB - A 56 year old African-American man presented to the emergency department with
dyspnea and dysphagia with drooling. On his initial evaluation, disproportionate
obesity of the face, neck and shoulders were noted. The patient's history was
significant for obstructive sleep apnea, end-stage renal disease, alcoholic liver
disease, pulmonary hypertension and alcoholic cardiomyopathy. He had multi-decade
history of heavy alcohol abuse, but quit drinking two years previously.
PMID- 28414691
TI - Mr-Proadm Elevation Upon Icu Admission Predicts the Outcome of Septic Patients
and is Correlated with Upcoming Fluid Overload.
AB - BACKGROUND: Among septic patients admitted to the intensive care unit (ICU),
early recognition of those with the highest risk of death is of paramount
importance. We evaluated the prognostic value of Procalcitonin (PCT), mid
regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT
ProET 1) concentrations. METHODS: This was a prospective cohort study, which
included 173 septic patient admitted to one ICU. Blood samples for biomarker
measurements were obtained upon admission and on day 5. The predictive value of
each biomarker regarding the risk of death at day 28 was assessed. The fluid
balance was evaluated from admission to day 5. RESULTS: All cause ICU mortality
was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated
in the non-survivors than in the survivors upon day 1. This was especially true
for MR-proADM (8.6 [5.9] vs. 4.4 [3.9] nmol/L; P < 0.0001) and for the CT-proET
1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The
best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR
proADM ratio as well (0.75 [0.67-0.85] and 0.82 [0.75-0.89]; 95% CI,
respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM
baseline levels and fluid balance over the 5-day period following ICU admission
were strongly correlated (Rho = 0.41; P < 0.001). CONCLUSIONS: In patients
admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of
short-term clinical outcome if compared with others. This could be related to its
ability to predict fluid sequestration.
PMID- 28414692
TI - Neuronal Fibers and Neurotransmitter Receptor Expression in the Human
Endolymphatic Sac.
AB - INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may
have multiple functions, including an ion-transport capacity comparable to the
kidney, an immunological capacity and a possible natriuretic capacity. Further,
there have been speculations of a yet undefined role in intracranial pressure
homeostasis. The anatomical location towards the sigmoid sinus would suggest a
possible endo- and/or paracrine signaling. However, neuronal connections may also
apply, but it remains very scarcely explored in the human ES. STUDY DESIGN: DNA
micro-arrays and immunohistochemistry were used for analyses of fresh human ES
tissue samples. METHODS: A total of 30 tissue samples from the human ES were
obtained during translabyrinthine surgery for vestibular schwannoma. Microarray
technology was used to investigate tissue sample gene expression, using adjacent
dura mater as control. The expression of genes specific for neuronal signaling
was determined and results for selected key molecules verified by
immunohistochemistry. Transmission electron microscopy was used for
ultrastructural analysis. RESULTS: For the transmission electron microscopy
analysis, a direct innervation of the ES was observed with unmyelinated fibers
imbedded in the ES epithelial lining. The microarrays confirmed, that several
molecules involved in neuronal signaling were found expressed significantly in
the ES DNA profile, such as the Cholecystokinin peptide and related receptors,
Dopamine receptors 2 and 5, vesicular monoamine transporter 2 (VMAT2), plasma
monoamine transporter (PMAT), and Serotonin 1D. All peptides were verified by
immunohistochemistry. CONCLUSIONS: Based on global gene expression profiling and
immuno-histochemical labeling, we conclude that the human ES expresses
neuropeptide receptors and monoamine transporters. Combined with the
ultrastructural demonstration of unmyelinated axons imbedded within the
epithelial lining, the findings suggest that neuro-signaling mechanisms are
involved in functions exerted by the ES.
PMID- 28414693
TI - Systematic Review on the Trial Period for Bone Conduction Devices in Single-Sided
Deafness: Rates and Reasons for Rejection.
AB - OBJECTIVE: To systematically review the literature to evaluate the trial period
of bone conduction devices (BCDs) for adult patients with single-sided deafness
(SSD). DATA SOURCES: The PubMed, Embase, and Cochrane Library databases were
searched from their inception up to August 15, 2016 for SSD, BCD, and their
synonyms. STUDY SELECTION: In total, 523 articles were retrieved, of which 12
satisfied the eligibility quality criteria. Our outcomes of interest were: 1) the
BCD implantation rejection percentage, 2) reasons to reject BCD implantation, and
3) possible prognostic factors predicting the trial outcome. DATA EXTRACTION AND
SYNTHESIS: At critical appraisal, six studies (n = 471 patients) scored a
moderate to high directness of evidence and a medium or low risk of bias and were
selected for data extraction. Due to heterogeneity between studies, pooling of
data for meta-analysis was not feasible. Therefore, results of studies were
summarized per outcome: 1) after the BCD trial, 32.0 to 69.6% of SSD patients
rejected BCD implantation, 2) the three main reasons for rejection were
experiencing limited benefit from the device, patients fearing or being unfit for
surgery and cosmetic aspects, 3) no clear prognostic factors predicting the trial
outcome could be identified. CONCLUSION: Roughly half of patients rejected BCD
implantation after a trial period. From the current literature it is unclear
which patients could benefit most from BCD implantation. High level of evidence
studies should be conducted to investigate possible prognostic factors that
predict the BCD trial outcome.
PMID- 28414694
TI - Ipsilesional Nystagmus Induced by Vibration in Subjects With Meniere's Disease or
Vestibular Schwannoma.
AB - OBJECTIVE: To analyze the frequency in which vibration-induced nystagmus (VIN)
with ipsilesional direction appears in subjects with Meniere's disease (MD) or
vestibular schwannoma (VS). STUDY DESIGN: Cross-sectional study. SETTING:
Tertiary referral center. PATIENTS: Fifty-two subjects with MD and 21 subjects
with vestibular schwannoma. INTERVENTION: Videonystagmographic recordings of VIN
at 30, 60, and 100 Hz. MAIN OUTCOME MEASURES: Direction and slow phase velocity
of VIN at 30, 60, and 100 Hz. RESULTS: Ipsilesional Nystagmus was observed in 8
of 52 subjects with MD (15.4%) and in 11 of 21 subjects affected of unilateral VS
(52.4%). Ipsilesional nystagmus was significantly higher in patients with VS (p =
0.003). The frequency of appearance of ipsilesional nystagmus in the subjects
with VS who has not been treated was significantly higher than those who
underwent radiosurgery (84.6% vs 0%, p = 0.046). CONCLUSION: Ipsilesional
vibration-induced Nystagmus can be present in subjects with vestibular deficits
caused by MD and VS.
PMID- 28414695
TI - Imaging Criteria to Predict Surgical Difficulties During Stapes Surgery.
AB - BACKGROUND AND PURPOSE: Stapes surgery for otosclerosis can be challenging if
access to the oval window niche is restricted. The aim of this study was to
determine the accuracy of the computed tomographic (CT) scan in the evaluation of
anatomical distances, and to analyze its reliability in predicting surgical
technical difficulties. MATERIAL AND METHODS: A total of 96 patients (101 ears)
were enrolled in a prospective study between 2012 and May 2015. During surgery,
we evaluated the distance D1 between the stapes and the facial nerve, distance D2
between the promontory and the facial nerve after ablation of the superstructure,
and the intraoperative discomfort of the surgeon. On preoperative CT scans, we
measured the width and depth of the oval window niche, and the angle formed by
two axes starting from the center-point of the footplate, the first tangential to
the superior wall of the promontory, and the second tangential to the inferior
wall of the fallopian canal. RESULTS: Intraoperative distances D1 and D2 were
correlated with the width of the oval window and with the facial-promontory angle
measured on imaging. CT scan measurements of the facial-promontory angle and
width of the oval window were associated with the degree of discomfort of the
surgeon. The cut-off threshold for intraoperative subjective discomfort was
computed as 1.1 mm for the width of the oval window niche, with a sensibility of
71% and a specificity of 84%. CONCLUSION: Preoperative imaging analysis of the
oval window width and the facialpromontory angle can predict operative difficulty
in otosclerosis surgery.
PMID- 28414696
TI - Decrease in Pneumococcal Otitis Media Cultures With Concomitant Increased
Antibiotic Susceptibility in the Pneumococcal Conjugate Vaccines Era.
AB - OBJECTIVE: To study the change in the incidence and antibiotic susceptibility
patterns of Streptococcus pneumoniae (Spn) in cultures obtained from children
with otitis media (OM) during the pneumococcal conjugate vaccines (PCVs) era.
STUDY DESIGN: Retrospective. SETTING: Secondary medical care center. PATIENTS:
Children less than 8 years who presented with OM and had positive pneumococcal
cultures during January 1, 2007 to December 12, 2014 were identified. Data
recorded included demographics, preadmission antibiotics, culture source, and
antibiotic susceptibility tests. We compared the pre-PCV years (2007-2008) with
the transition years (2009-2011) and the post-PCV13 years (2012-2014).
INTERVENTIONS: PCV7 (2009), PCV13 (2010), therapeutic. MAIN OUTCOME MEASURE(S):
Annual rate of Spn cultures, antibiotic susceptibility patterns. RESULTS: We
identified 134 children (76 boys, 57%) who contributed 162 pneumococcal cultures.
There was a downward trend in the annual incidence rate of Spn cultures between
the pre-PCV years, transition years, and post-PCV13 years: 11.12, 8.48, and
4.11/1000 hospitalized children/year, respectively (p = 0.08, p = 0.04). Had
there been no interventions, and based on the 2007 to 2009 average, the observed
over the expected Spn cultures ratio rates for 2010 to 2014 were 0.59, 0.45,
0.40, 0.40, and 0.25, respectively. In parallel, the susceptibility of Spn
strains to four commonly tested antibiotics significantly increased from the pre
PCV years to the transition years and the post-PCV13 years. In each period, Spn
strains were penicillin sensitive in 37, 51, and 100%; for erythromycin, 46, 71,
and 82%; for trimethoprim/sulfamethoxazole, 32, 71, and 97%; and for ceftriaxone,
95, 96, and 100%, respectively. CONCLUSION: The introduction of PCVs
significantly decreased the incidence rate of pneumococcal OM, and increased Spn
susceptibility to common antibiotics.
PMID- 28414697
TI - Feasibility of Transvesical Robotic VVF Repair in Porcine Model.
AB - Extraperitoneal transvesicoscopic vesicovaginal fistula (VVF) repair has received
limited use because of its narrow working space, longer operation time, and
technical difficulty. The present study describes the feasibility of robotic
assisted transvesicoscopic VVF repair in an animal model. Two Yorkshire swine
underwent robotic-assisted laparoscopic (RAL) VVF repair. With the 4 trocars, an
artificial VVF was made in the supratrigonal area and VVF repair was performed in
3 layers as in open VVF repair methods. The mean operation time was 108 minutes.
The operation time was prolonged in 1 case due to weak fixation of bladder to
anterior abdominal wall. Equipment interference did not occur. Tissue
manipulation and suturing were easy. The results of this study suggest that
extraperitoneal RAL procedures for VVF repair may be an effective minimally
invasive modality with reduced morbidity. A shorter operation time and easy
suturing technique were the distinct merits of the extraperitoneal RAL technique.
PMID- 28414698
TI - The Feasibility of Thoracoscopic Resection in Bronchiectasis.
AB - INTRODUCTION: Minimally invasive surgery is the treatment of choice in early
stage lung cancer. However, experience in infectious lung disease, primarily
bronchiectasis, is limited probably because of the presence of dense pleural
adhesions, multiple lymph nodes, and spiral bronchial arteries. The present study
shows our experience of video-assisted thoracoscopic surgery (VATS) lobectomy and
segmentectomy in the treatment of bronchiectasis. MATERIALS AND METHODS: Patients
who underwent VATS lobectomy or segmentectomy in our clinic between April 2008
and 2015 were retrospectively evaluated. Surgery was indicated in patients with
radiologic localized bronchiectasis who also had a history of recurrent lower
respiratory tract infection or expectorating mucopurulent secretion. The patients
were analyzed in terms of age, sex, thoracotomy conversion rate, postoperative
drainage amount, chest tube removal time, length of hospital stay, morbidity, and
mortality. RESULTS: A total of 44 patients initially underwent VATS pulmonary
anatomic resection and 41 procedures were completed on 40 patients. One patient
had bilateral resection. Fifteen patients were male individuals and 26 were
female individuals. The average age was 31.4 (15 to 57) years. Forty lobectomies
and 1 segmentectomy were performed. The conversion rate was 6.8%. VATS was
performed on 28 patients by 3 ports, 8 patients by 2 ports, and 5 patients by a
single port. In terms of anatomic resections, 18 patients underwent left lower
lobectomy, 8 right lower lobectomy, 8 middle lobectomy, 6 right upper lobectomy,
and 1 patient underwent lingular segmentectomy. No major postoperative
complication or mortality was observed. Prolonged air leak was observed in 2
patients and subcutaneous emphysema occurred in 2 patients. The average
postoperative drainage amount, chest tube removal time, and length of hospital
stay were 320 mL, 3.1 (1 to 11) days, and 4.6 (2 to 11) days, respectively.
CONCLUSIONS: VATS pulmonary resection is a safe, feasible, and effective
treatment in the surgery of bronchiectasis with low morbidity and mortality
rates. Moreover, because of cosmetic results, patients with benign diseases such
as bronchiectasis could be initiated by minimally invasive surgery options just
like patients with malignancies.
PMID- 28414699
TI - Etiology of Leaks Following Sleeve Gastrectomy: Current Evidence.
AB - PURPOSE: The purpose of this paper is to study the causes of leaks following
sleeve gastrectomy (SG). MATERIALS AND METHODS: Pubmed was searched during
January 2016 for publications reporting leak after SG. A total of 205
publications were identified, of which 17 papers were selected. RESULTS: In about
3018 patients, reinforcement was used compared with 4595 patients, in whom no
reinforcement was applied; both groups were representing matched bariatric
populations. The use of reinforcement/buttressing has resulted in different rates
of leaks ranging from 0% to 3.9%; whereas with no reinforcement/buttressing, the
leak rate was 0.16% to 3.5%. The use of reinforcement/buttressing did not result
in reduction of leak to a statistical significance although the trend was
suggesting so (P=0.06), whereas no reinforcement/buttressing did not
statistically increase the leak rate (P=0.10). CONCLUSIONS: No statistical
significant difference of leak with or without reinforcement. This mean case
complexity and surgical technique and experience are the sole factors for leaks
following SG.
PMID- 28414700
TI - Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in
Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic
Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.
AB - This randomized trial investigated whether a 2-dose administration of intravenous
ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective
than a single-dose administration in preventing postoperative nausea and vomiting
(PONV) in 89 patients who were scheduled to undergo laparoscopic operation for
benign gynecologic diseases and to receive intravenous patient-controlled
analgesia for relief of postoperative pain. After assignment at a ratio of 1:1,
intravenous ramosetron (0.3 mg) was initially administered at the end of skin
closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were
administered to the study and control groups, respectively, at 4 hours after the
operation. The baseline and operative characteristics were similar between the
groups. The incidence of PONV during the 24-hour period after operation which was
assessed as the primary endpoint did not differ between the groups. No serious
adverse events occurred in either group. A 2-dose administration of intravenous
ramosetron may not be superior to a single-dose administration in preventing PONV
in patients undergoing laparoscopic operation for benign gynecologic diseases.
PMID- 28414701
TI - Complications of Minimally Invasive Surgery in Children: A Prospective Morbidity
and Mortality Analysis Using the Clavien-Dindo Classification.
AB - There is a lack of information about evaluation of pediatric minimal access
surgery complications; the Clavien-Dindo classification was never used for a
large series of laparoscopic and thoracoscopic pediatric procedures. With a
prospective Morbidity and Mortality database, all the minimal access surgical
procedures carried out between 2012 and 2016 were included in this study.
Statistical analyses were used to valuate modification of surgical techniques in
to 2 periods (period 1: January 2012 to February 2014; period 2: February 2014 to
February 2016). A total of 1374 minimal access procedures were performed on 1371
patients. The overall complication rate was 2.9%. No differences, in terms of
complications, were observed between elective and emergency procedures (P=0.3).
There was a significant difference between the complication rate of thoracoscopic
surgery (P=0.027). These results provide the relevance of adequate recording
system and standardized classification for analyses and reduction of
complications for pediatric minimal access procedures.
PMID- 28414702
TI - Minimally Invasive Treatment for Appendiceal Mass Formed After Acute Perforated
Appendicitis.
AB - The optimal treatment for appendiceal mass formed after appendiceal rupture due
to acute appendicitis is surrounded with controversy. The treatment strategy
ranges from open surgery (emergency or interval appendectomy), laparoscopic
appendectomy, and image-guided drainage, to conservative treatment with or
without antibiotics. Nonsurgical treatment (including conservative and drainage
treatment), followed by interval appendectomy to prevent recurrence, is the
traditional management of these patients. The need for interval appendectomy
after a successful conservative or/and image-guided drainage treatment, has
recently been questioned as the risk of recurrence is relatively small. Several
authors consider that even in cases involving only ambulatory follow-up
observation, without interval surgery after conservative management, the
recurrence rate and risks of missing underlying pathologies were not high. This
article evaluates the minimally invasive treatment modalities in the management
of appendiceal mass, risk of undetected serious disease, and the need for
interval appendectomy to prevent recurrence.
PMID- 28414704
TI - An updated view on the reliability of different protocols for the assessment of
conditioned pain modulation.
PMID- 28414703
TI - Recruitment, Methods, and Descriptive Results of a Physiologic Assessment of
Latino Farmworkers: The California Heat Illness Prevention Study.
AB - OBJECTIVE: The California heat illness prevention study (CHIPS) devised
methodology and collected physiological data to assess heat related illness (HRI)
risk in Latino farmworkers. METHODS: Bilingual researchers monitored HRI across a
workshift, recording core temperature, work rate (metabolic equivalents [METs]),
and heart rate at minute intervals. Hydration status was assessed by changes in
weight and blood osmolality. Personal data loggers and a weather station measured
exposure to heat. Interviewer administered questionnaires were used to collect
demographic and occupational information. RESULTS: California farmworkers (n =
588) were assessed. Acceptable quality data was obtained from 80% of participants
(core temperature) to 100% of participants (weight change). Workers (8.3%)
experienced a core body temperature more than or equal to 38.5 degrees C and
11.8% experienced dehydration (lost more than 1.5% of body weight). CONCLUSIONS:
Methodology is presented for the first comprehensive physiological assessment of
HRI risk in California farmworkers.
PMID- 28414706
TI - Reply.
PMID- 28414705
TI - Small fiber neuropathy or small fiber pathology?
PMID- 28414707
TI - Supporting the updated definition of pain. But what about labour pain?
PMID- 28414708
TI - Reply.
PMID- 28414709
TI - Robotic Surgery: Fast Forward to Telemedicine.
AB - Since the realization that certain maladies can be corrected via surgical
techniques, we have been consumed by the desire to constantly advance the tools
of surgery, as well as the techniques. In recent times, computer-assisted
surgical tools have emerged and are growing in their use. The Puma 560 emerged in
1985 for brain biopsies and laparoscopic surgery. Prostatic surgery was performed
by the Probot in 1988. In 1992, fittings in the femur were placed using the
ROBODOC. These early robotic endeavors gave rise to AESOP, ZEUS and the
relatively intuitive da Vinci(r) Surgical System. These advances reflect the
rapid growth of knowledge in the technology sector. These ever increasingly
complex robotic-driven procedures are favored because this surgery provides a
less invasive and therefore more tolerable "surgical" procedure for patients. In
turn, these less invasive experiences may also allow for faster recovery times,
reducing hospital stays and potentially costs. Importantly, this technology is
accompanied by the development of more targeted surgical interventions. On the
negative side, these technologies are initially expensive. However, as is always
the case, there is hope that future devices will be more economical as more
institutions invest. Another trend which may reduce costs is in the design of the
robotic devices to incorporate a common central core of technology, to which
other sub-devices can be attached, offering additional cost savings while
enhancing flexibility.
PMID- 28414710
TI - Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid
thioesters.
AB - Biotin is an essential vitamin in plants and mammals, functioning as the carbon
dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA
synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring
the integrity of the carbon chain in biotin synthesis. BioW catalyzes the
condensation of pimelic acid (C7 dicarboxylic acid) with CoASH in an ATP
dependent manner to form pimeloyl-CoA, the first dedicated biotin building block.
Multiple structures of Bacillus subtilis BioW together capture all three
substrates, as well as the intermediate pimeloyl-adenylate and product
pyrophosphate (PPi), indicating that the enzyme uses an internal ruler to select
the correct dicarboxylic acid substrate. Both the catalytic mechanism and the
surprising stability of the adenylate intermediate were rationalized through site
directed mutagenesis. Building on this understanding, BioW was engineered to
synthesize high-value heptanoyl (C7) and octanoyl (C8) monocarboxylic acid-CoA
and C8 dicarboxylic-CoA products, highlighting the enzyme's synthetic potential.
PMID- 28414711
TI - The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming
enzymes.
AB - Reactions that activate carboxylates through acyl-adenylate intermediates are
found throughout biology and include acyl- and aryl-CoA synthetases and tRNA
synthetases. Here we describe the characterization of Aquifex aeolicus BioW,
which represents a new protein fold within the superfamily of adenylating
enzymes. Substrate-bound structures identified the enzyme active site and
elucidated the mechanistic strategy for conjugating CoA to the seven-carbon
alpha,omega-dicarboxylate pimelate, a biotin precursor. Proper position of
reactive groups for the two half-reactions is achieved solely through movements
of active site residues, as confirmed by site-directed mutational analysis. The
ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent
of pre-transfer proofreading observed in some tRNA synthetases, and we show that
this activity can be abolished by mutation of a single residue. These studies
illustrate how BioW can carry out three different biologically prevalent chemical
reactions (adenylation, thioesterification, and proofreading) in the context of a
new protein fold.
PMID- 28414712
TI - The need for a worldwide consensus for cell line authentication: Experience
implementing a mandatory requirement at the International Journal of Cancer.
AB - Cell lines are used in life science research worldwide as biological surrogates.
All cell lines are subject to major limitations when used as research tools,
including (i) cross-contamination with other cells cultured in the same
laboratory environment and (ii) evolution in vitro that renders a given cell line
inappropriate as a surrogate for a specific biological hypothesis. There is ample
evidence that cross-contamination or phenotypic drift of cells in culture can
generate irreproducible or misleading data. A small number of scientific journals
the International Journal of Cancer being at the forefront-and funding agencies
have recently moved forward to ask for obligatory cell line authentication data.
The history of implementing such rules by the International Journal of Cancer
exemplifies the difficulties encountered when installing mandatory quality
measures in life sciences.
PMID- 28414713
TI - Less fear, more diversity.
AB - Fear is an instinctual response that's adaptive and critical for survival when it
is short-lived but can lead to anxiety disorders when chronic. Studying how the
brain controls our fears helps us understand the mechanisms required to recover
from traumatic experiences and what goes wrong when we don't. Research in rodents
has identified neural circuits and molecular mechanisms regulating fear
expression. Rodent work has been amenable to translation to humans and has led to
improvements in clinical therapies for anxiety disorders. The societal benefit of
this type of research is magnified when performed in minority-serving
institutions, offering high-caliber training opportunities to increase ethnic
diversity in science.
PMID- 28414714
TI - Excess atherosclerosis in systemic lupus erythematosus,-A matter of renal
involvement: Case control study of 281 SLE patients and 281 individually matched
population controls.
AB - BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which
predominantly affects young females (90%). SLE is associated with a shorter life
expectancy than in the general population. Standardized mortality ratios (SMR) of
2.4 have been reported, which is comparable to diabetes. In modern societies
cardiovascular disease (CVD) is the major cause of premature mortality.
Accelerated atherosclerosis is generally assumed to be the underlying cause for
SLE related CVD. However, previous studies diverge regarding whether
atherosclerosis is more common in SLE than in controls. With this in mind and
based on own clinical experience we hypothesized that accelerated atherosclerosis
is not a general feature of SLE, but prevails in SLE subgroups. METHODS: 281 SLE
patients and 281 individually age and sex matched population controls, were
investigated clinically. Fasting blood samples and risk factor data were
collected. All participants were subject to B-mode ultrasonography of the carotid
arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were
recorded. Two SLE subgroups previously described to be at high CVD risk; 1)
patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL),
and one subgroup reported to be at comparatively lower CVD risk; patients
positive for Sjogren's syndrome antigens A/B (SSA/SSB) antibodies were analyzed
separately in comparison with their respective matched controls. RESULTS: Median
age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart,
cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%,
p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients
had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age
adjustment plaques, but not mIMT, remained associated with previous CVD events.
Therefore we focused further analyses on plaques, a more robust measure of
atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB
(40%) positive patients, had more plaques than their respective controls (23% vs.
11%, p = 0.008). Notably, patients with nephritis were younger than other SLE
patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we
performed an age-matched nested case-control analysis, which demonstrated that
patients with nephritis had twice as often plaques (23%) as both non-nephritis
patients (11%, p = 0.038) and controls (12%, p = 0.035). CONCLUSIONS: In SLE
excess carotid plaques are essentially confined to the SLE subgroup with
nephritis. This subgroup had plaques twice as often as age-matched non-nephritis
SLE patients and population controls. Non-nephritis SLE patients, including the
aPL positive subgroup, which has a high CVD risk, had similar prevalence of
plaques as controls. To prevent later CVD events, this novel observation calls
for risk factor screening and initiation of anti-atherosclerotic treatment
selectively in SLE nephritis patients. Preferably at nephritis onset, which is
often at a young age. In a general perspective this study demonstrates the
importance to perform careful clinical subgroup analyses when investigating
heterogeneous, hitherto not clearly defined, conditions like SLE.
PMID- 28414716
TI - Dynamics of adaptive immunity against phage in bacterial populations.
AB - The CRISPR (clustered regularly interspaced short palindromic repeats) mechanism
allows bacteria to adaptively defend against phages by acquiring short genomic
sequences (spacers) that target specific sequences in the viral genome. We
propose a population dynamical model where immunity can be both acquired and
lost. The model predicts regimes where bacterial and phage populations can co
exist, others where the populations exhibit damped oscillations, and still others
where one population is driven to extinction. Our model considers two key
parameters: (1) ease of acquisition and (2) spacer effectiveness in conferring
immunity. Analytical calculations and numerical simulations show that if spacers
differ mainly in ease of acquisition, or if the probability of acquiring them is
sufficiently high, bacteria develop a diverse population of spacers. On the other
hand, if spacers differ mainly in their effectiveness, their final distribution
will be highly peaked, akin to a "winner-take-all" scenario, leading to a
specialized spacer distribution. Bacteria can interpolate between these limiting
behaviors by actively tuning their overall acquisition probability.
PMID- 28414715
TI - Transcriptional regulatory logic of the diurnal cycle in the mouse liver.
AB - Many organisms exhibit temporal rhythms in gene expression that propel diurnal
cycles in physiology. In the liver of mammals, these rhythms are controlled by
transcription-translation feedback loops of the core circadian clock and by
feeding-fasting cycles. To better understand the regulatory interplay between the
circadian clock and feeding rhythms, we mapped DNase I hypersensitive sites
(DHSs) in the mouse liver during a diurnal cycle. The intensity of DNase I
cleavages cycled at a substantial fraction of all DHSs, suggesting that DHSs
harbor regulatory elements that control rhythmic transcription. Using chromatin
immunoprecipitation followed by DNA sequencing (ChIP-seq), we found that
hypersensitivity cycled in phase with RNA polymerase II (Pol II) loading and
H3K27ac histone marks. We then combined the DHSs with temporal Pol II profiles in
wild-type (WT) and Bmal1-/- livers to computationally identify transcription
factors through which the core clock and feeding-fasting cycles control diurnal
rhythms in transcription. While a similar number of mRNAs accumulated
rhythmically in Bmal1-/- compared to WT livers, the amplitudes in Bmal1-/- were
generally lower. The residual rhythms in Bmal1-/- reflected transcriptional
regulators mediating feeding-fasting responses as well as responses to rhythmic
systemic signals. Finally, the analysis of DNase I cuts at nucleotide resolution
showed dynamically changing footprints consistent with dynamic binding of
CLOCK:BMAL1 complexes. Structural modeling suggested that these footprints are
driven by a transient heterotetramer binding configuration at peak activity.
Together, our temporal DNase I mappings allowed us to decipher the global
regulation of diurnal transcription rhythms in the mouse liver.
PMID- 28414717
TI - A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent
bulk endocytosis.
AB - Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis
(ADBE) are two predominant forms of synaptic vesicle (SV) endocytosis, elicited
by moderate and strong stimuli, respectively. They are tightly coupled with
exocytosis for sustained neurotransmission. However, the underlying mechanisms
are ill defined. We previously reported that the Flower (Fwe) Ca2+ channel
present in SVs is incorporated into the periactive zone upon SV fusion, where it
triggers CME, thus coupling exocytosis to CME. Here, we show that Fwe also
promotes ADBE. Intriguingly, the effects of Fwe on CME and ADBE depend on the
strength of the stimulus. Upon mild stimulation, Fwe controls CME independently
of Ca2+ channeling. However, upon strong stimulation, Fwe triggers a Ca2+ influx
that initiates ADBE. Moreover, knockout of rodent fwe in cultured rat hippocampal
neurons impairs but does not completely abolish CME, similar to the loss of
Drosophila fwe at the neuromuscular junction, suggesting that Fwe plays a
regulatory role in regulating CME across species. In addition, the function of
Fwe in ADBE is conserved at mammalian central synapses. Hence, Fwe exerts
different effects in response to different stimulus strengths to control two
major modes of endocytosis.
PMID- 28414718
TI - Achieving global perfect homeostasis through transporter regulation.
AB - Nutrient homeostasis-the maintenance of relatively constant internal nutrient
concentrations in fluctuating external environments-is essential to the survival
of most organisms. Transcriptional regulation of plasma membrane transporters by
internal nutrient concentrations is typically assumed to be the main mechanism by
which homeostasis is achieved. While this mechanism is homeostatic we show that
it does not achieve global perfect homeostasis-a condition where internal
nutrient concentrations are completely independent of external nutrient
concentrations for all external nutrient concentrations. We show that the
criterion for global perfect homeostasis is that transporter levels must be
inversely proportional to net nutrient flux into the cell and that downregulation
of active transporters (activity-dependent regulation) is a simple and
biologically plausible mechanism that meets this criterion. Activity-dependent
transporter regulation creates a trade-off between robustness and efficiency,
i.e., the system's ability to withstand perturbation in external nutrients and
the transporter production rate needed to maintain homeostasis. Additionally, we
show that a system that utilizes both activity-dependent transporter
downregulation and regulation of transporter synthesis by internal nutrient
levels can create a system that mitigates the shortcomings of each of the
individual mechanisms. This analysis highlights the utility of activity-dependent
regulation in achieving homeostasis and calls for a re-examination of the
mechanisms of regulation of other homeostatic systems.
PMID- 28414719
TI - Crucial role of estrogen for the mammalian female in regulating semen coagulation
and liquefaction in vivo.
AB - Semen liquefaction changes semen from a gel-like to watery consistency and is
required for sperm to gain mobility and swim to the fertilization site in the
Fallopian tubes. Kallikrein-related peptidases 3 (KLK3) and other kallikrein
related peptidases from male prostate glands are responsible for semen
liquefaction by cleaving gel-forming proteins (semenogelin and collagen). In a
physiological context, the liquefaction process occurs within the female
reproductive tract. How seminal proteins interact with the female reproductive
environment is still largely unexplored. We previously reported that conditional
genetic ablation of Esr1 (estrogen receptor alpha) in the epithelial cells of the
female reproductive tract (Wnt7aCre/+;Esr1f/f) causes female infertility, partly
due to a drastic reduction in the number of motile sperm entering the oviduct. In
this study, we found that post-ejaculated semen from fertile wild-type males was
solidified and the sperm were entrapped in Wnt7aCre/+;Esr1f/f uteri, compared to
the watery semen (liquefied) found in Esr1f/f controls. In addition, semenogelin
and collagen were not degraded in Wnt7aCre/+;Esr1f/f uteri. Amongst multiple gene
families aberrantly expressed in the absence of epithelial ESR1, we have
identified that a lack of Klks in the uterus is a potential cause for the
liquefaction defect. Pharmacological inhibition of KLKs in the uterus replicated
the phenotype observed in Wnt7aCre/+;Esr1f/f uteri, suggesting that loss of
uterine and seminal KLK function causes this liquefaction defect. In human
cervical cell culture, expression of several KLKs and their inhibitors (SPINKs)
was regulated by estrogen in an ESR1-dependent manner. Our study demonstrates
that estrogen/ESR1 signaling in the female reproductive tract plays an
indispensable role in normal semen liquefaction, providing fundamental evidence
that exposure of post-ejaculated semen to the suboptimal microenvironment in the
female reproductive tract leads to faulty liquefaction and subsequently causes a
fertility defect.
PMID- 28414720
TI - Land altitude, slope, and coverage as risk factors for Porcine Reproductive and
Respiratory Syndrome (PRRS) outbreaks in the United States.
AB - Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most
impactful disease on the North American swine industry. The Swine Health
Monitoring Project (SHMP) is a national volunteer initiative aimed at monitoring
incidence and, ultimately, supporting swine disease control, including PRRS. Data
collected through the SHMP currently represents approximately 42% of the sow
population of the United States. The objective of the study here was to
investigate the association between geographical factors (including land
elevation, and land coverage) and PRRS incidence as recorded in the SHMP. Weekly
PRRS status data from sites participating in the SHMP from 2009 to 2016 (n = 706)
was assessed. Number of PRRS outbreaks, years of participation in the SHMP, and
site location were collected from the SHMP database. Environmental features
hypothesized to influence PRRS risk included land coverage (cultivated areas,
shrubs and trees), land altitude (in meters above sea level) and land slope (in
degrees compared to surrounding areas). Other risk factors considered included
region, production system to which the site belonged, herd size, and swine
density in the area in which the site was located. Land-related variables and pig
density were captured in raster format from a number of sources and extracted to
points (farm locations). A mixed-effects Poisson regression model was built; and
dependence among sites that belonged to a given production system was accounted
for using a random effect at the system level. The annual mean and median number
of outbreaks per farm was 1.38 (SD: 1.6), and 1 (IQR: 2.0), respectively. The
maximum annual number of outbreaks per farm was 9, and approximately 40% of the
farms did not report any outbreak. Results from the final multivariable model
suggested that increments of swine density and herd size increased the risk for
PRRS outbreaks (P < 0.01). Even though altitude (meters above sea level) was not
significant in the final model, farms located in terrains with a slope of 9% or
higher had lower rates of PRRS outbreaks compared to farms located in terrains
with slopes lower than 2% (P < 0.01). Finally, being located in an area of
shrubs/ herbaceous cover and trees lowered the incidence rate of PRRS outbreaks
compared to being located in cultivated/ managed areas (P < 0.05). In conclusion,
highly inclined terrains were associated with fewer PRRS outbreaks in US sow
farms, as was the presence of shrubs and trees when compared to cultivated/
managed areas. Influence of terrain characteristics on spread of airborne
diseases, such as PRRS, may help to predicting disease risk, and effective
planning of measures intended to mitigate and prevent risk of infection.
PMID- 28414721
TI - A novel smart navigation system for intramedullary nailing in orthopedic surgery.
AB - This paper proposes a novel smart surgical navigation system for intramedullary
nailing in orthopedic surgery. Using a handle-integrated laser guidance module,
the system can target a drill insertion point onto skin, indicating an accurate
target position to perpendicularly access an invisible distal hole. The proposed
handle-integration-based fixation of the laser guidance module precisely defines
the relative position of the module with respect to the distal hole.
Consequently, unlike conventional systems, the proposed system can indicate the
target insertion point without any help from bulky and costly external position
tracking equipment that is usually required for compensating disturbances
generated by external impacts. After insertion, a correct drilling direction
toward the distal hole is guided by real-time drilling angle measurement modules
one integrated with the nail handle and the other with the drill body. Each
module contains a 9-axis inertial sensor and a Bluetooth communication device.
These two modules work together to provide real-time drilling angle data,
allowing calculation of the directional error toward the center of the distal
hole in real time. The proposed system removes the need for fluoroscopy and
provides a compact and cost-effective solution compared with conventional
systems.
PMID- 28414722
TI - Re-visiting the tympanic membrane vicinity as core body temperature measurement
site.
AB - Core body temperature (CBT) is an important and commonly used indicator of human
health and endurance performance. A rise in baseline CBT can be attributed to an
onset of flu, infection or even thermoregulatory failure when it becomes
excessive. Sites which have been used for measurement of CBT include the
pulmonary artery, the esophagus, the rectum and the tympanic membrane. Among
them, the tympanic membrane is an attractive measurement site for CBT due to its
unobtrusive nature and ease of measurement facilitated, especially when
continuous CBT measurements are needed for monitoring such as during military,
occupational and sporting settings. However, to-date, there are still polarizing
views on the suitability of tympanic membrane as a CBT site. This paper will
revisit a number of key unresolved issues in the literature and also presents,
for the first time, a benchmark of the middle ear temperature against temperature
measurements from other sites. Results from experiments carried out on human and
primate subjects will be presented to draw a fresh set of insights against the
backdrop of hypotheses and controversies.
PMID- 28414723
TI - Prevalence and determinants of stereotypic behaviours and physiological stress
among tigers and leopards in Indian zoos.
AB - India's charismatic wildlife species are facing immense pressure from
anthropogenic-induced environmental perturbations. Zoos play a major role in the
conservation of threatened species, but their adaptation in captivity is posing a
major challenge globally. Stress from inadequate adaptation could lead to
suppression of cognitive functioning and increased display of stereotypic
behaviour. It is thus necessary to measure biological traits like behaviour,
stress physiology, and contextual factors driving the animals maintained at zoos.
In this study, we assessed stereotypic behaviour and stress physiology employing
standard behaviour scoring, non-invasive stress monitoring, and their contextual
drivers in a sub-population of two large felid species managed in six Indian
zoos. The prevalence and intensity of stereotypic behaviours and levels of faecal
corticosterone metabolites (FCM) were ascertained among 41 Royal Bengal tigers
Panthera tigris tigris and 21 Indian leopards Panthera pardus fusca between April
2014 and March 2015. Behavioural observations showed that tigers spent more time
stereotyping (12%) than leopards (7%) during daylight hours. Stress levels
assessed using FCM revealed that tigers (23.6 +/- 1.62 ng/g) had marginally lower
level of corticosterone metabolites than leopards (27.2 +/-1.36 ng/g).
Stereotypic behaviour increased significantly with FCM level when the effect of
heath status was controlled in tigers, and the effects tree cover, stone, den and
keeper attitude controlled in leopards. Comparison of stereotypes of tigers with
various biological and environmental factors using binary logistic regression
revealed that stereotypic prevalence decreased with increased enclosure size, and
enclosure enrichments like presence of pools and stones, when managed socially
with conspecifics, and with positive keeper attitude, these factors accounting
for 43% of variations in stereotypic prevalence among tigers. Stereotype among
leopards was significantly absent when associated with increased tree cover and
presence of pool, and den in the enclosure, age and among zoo-born than wild-born
ones. These factors explain 81% of variations in stereotypic prevalence in them.
A comparison of FCM levels with context-dependent factors revealed that stress
levels among tigers decreased significantly with enclosure size and with
individuals from nil to low, and severity of health issues. These factors explain
64% of variations in FCM levels. In leopards, the presence of stones in the
enclosure and keepers with positive attitude resulted in significant decrease in
FCM levels, these factors together accounting for 94% of variations. Multiple
regressions on selected variables based on Factor Analysis of Mixed Data showed
that in tigers the intensity of stereotype decreased significantly with enclosure
size, sociality and positive keeper attitude and FCM level with health problems.
Similarly, analyses in leopards revealed that intensity of stereotype decreased
significantly with tree cover, age and FCM level with positive keeper attitude.
Overall, our study suggests that to reduce stereotypes and stress level, tigers
in captivity should be managed in larger enclosures enriched with pool, and
stones, and in appropriate social conditions with adequate veterinary care.
Leopards should be managed in enclosures with dense tree cover, pool, stones and
den. Positive keeper attitude plays a crucial role in the welfare of both the
species in captivity. Our study is promising and is comparable with their natural
behaviour in the wild; for example, tigers require larger natural habitats, while
leopards can manage even with smaller isolated patches but with dense vegetation
cover.
PMID- 28414724
TI - Serine protease Bm-SP142 was differentially expressed in resistant and
susceptible Bombyx mori strains, involving in the defence response to viral
infection.
AB - Bm-SP142 is a 35 kDa protease in the silkworm, but its exact functions remain
unknown. In this study, sequence alignment revealed that the His-Asp-Ser
catalytic triad is embedded in the TAAHC-DIAL-GDSGGP sequence motif, establishing
Bm-SP142 as a serine protease. Soluble recombinant GST-BmSP142 was expressed and
purified, and serine protease activity was confirmed in vitro. RT-qPCR results
indicated that Bm-SP142 was mainly expressed in the middle part of the silkworm
midgut, and Bm-SP142 transcripts were significantly up-regulated at 24 hours post
infection (hpi) in BmBDV-resistant strains (798) inoculated with BmBDV and BmNPV
resistant strains (NB) inoculated with BmNPV, but not in BmBDV-susceptible
strains (306). Surprisingly, transcripts were significantly down-regulated at 12
hpi in BmNPV-susceptible strains (HuaBa 35) inoculated with BmNPV, compared with
healthy silkworms. Recombinant BmNPV treated with purified Bm-SP142 effectively
impaired its ability to infect BmN cells, and Bm-SP142 decreases the efficiency
of BmNPV and BmBDV propagation in silkworms. Furthermore, overexpression of Bm
SP142 in BmN cells inhibited viral propagation.
PMID- 28414725
TI - Evolution of EBV seroprevalence and primary infection age in a French hospital
and a city laboratory network, 2000-2016.
AB - BACKGROUND: According to rare studies, the age at EBV primary infection (PI) has
recently risen in some developed countries. A later age at infection is generally
considered a risk factor for severe EBV PI, although few studies exist on this
subject. Our investigation aimed to determine whether EBV seroprevalence and EBV
PI epidemiology have evolved in France, and to what extent age and infection
intensity (regarding biological parameters) are correlated. METHODS AND FINDINGS:
We conducted a retrospective study of the following EBV serological tests
databases: tests carried out at Grenoble University Hospital (2000-2016) (n =
53,553); and tests carried out by a network of city laboratories in Grenoble area
(2008-2015) (n = 27,485). The hospital population showed a continuous,
significant decrease in EBV seroprevalence over the studied period for patients
aged 20 and over (p<0.01). The seroprevalence also decreased for different age
classes (<10, 15-19, 20-30, and 30-40 years old) over the periods 2001-2005, 2006
2010, and 2011-2015. Consistently, the age at PI was significantly higher in the
years 2008-2015 than in the years 2001-2007 (15.6+/-12.0 vs. 13.7+/-11.0; p =
0.03). The city laboratory population showed the same trend of decreasing
seroprevalence (p = 0.06); no significant variations in age at PI were observed.
The age at PI was positively correlated with ASAT, ALAT, gammaGT, and bilirubin
blood levels (p<0.01) and negatively correlated with platelet counts (p<0.05).
CONCLUSION: In the last 15 years, the age at EBV PI has increased, whereas
seroprevalence has decreased. Moreover, our findings confirm the positive
correlation between age and biological abnormalities. Taken together, these
results suggest that the incidence of severe EBV PI will increase in the future.
PMID- 28414727
TI - Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form
of the parasite.
AB - The mitochondrial (mt) FoF1-ATP synthase of the digenetic parasite, Trypanosoma
brucei, generates ATP during the insect procyclic form (PF), but becomes a
perpetual consumer of ATP in the mammalian bloodstream form (BF), which lacks a
canonical respiratory chain. This unconventional dependence on FoF1-ATPase is
required to maintain the essential mt membrane potential (Deltapsim). Normally,
ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic
cells experience sporadic hypoxic conditions, during which this compulsory
function quickly depletes the cellular ATP pool. To protect against this cellular
treason, the highly conserved inhibitory factor 1 (IF1) binds the enzyme in a
manner that solely inhibits the hydrolytic activity. Intriguingly, we were able
to identify the IF1 homolog in T. brucei (TbIF1), but determined that its
expression in the mitochondrion is tightly regulated throughout the life cycle as
it is only detected in PF cells. TbIF1 appears to primarily function as an
emergency brake in PF cells, where it prevented the restoration of the Deltapsim
by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1
overexpression specifically inhibits the hydrolytic activity but not the
synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore,
low MUM amounts of recombinant TbIF1 achieve the same inhibition of total mt
ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin.
Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as
the indispensable Deltapsim collapsed due to inhibited FoF1-ATPase. In summary,
we provide evidence that T. brucei harbors a natural and potent unidirectional
inhibitor of the vital FoF1-ATPase activity that can be exploited for future
structure-based drug design.
PMID- 28414726
TI - Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by
differentially regulating cytotoxic T and myeloid-derived suppressor cells.
AB - Post-surgical tumor recurrence is a common problem in cancer treatment. In the
present study, the role of neem leaf glycoprotein (NLGP), a novel
immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was
examined. Data suggest that NLGP prevents tumor recurrence after surgical removal
of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP
treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased
population of suppressor cells, especially myeloid-derived suppressor cells
(MDSCs) was observed. NLGP-treated CD8+ T cells showed greater cytotoxicity
towards tumor-derived MDSCs and supernatants from the same CD8+ T cell culture
caused upregulation of FasR and downregulation of cFLIP in MDSCs. To elucidate
the role of CD8+ T cells, specifically in association with the downregulation in
MDSCs, CD8+ T cells were depleted in vivo before NLGP immunization in surgically
tumor removed mice and tumor recurrence was noted. These mice also exhibited
increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased
cFLIP expression. In conclusion, it can be stated that NLGP, by activating CD8+ T
cells, down regulates the proportion of MDSCs. Accordingly, suppressive effects
of MDSCs on CD8+ T cells are minimized and optimum immune surveillance in tumor
hosts is maintained to eliminate the residual tumor mass appearing during
recurrence.
PMID- 28414728
TI - Clown-care reduces pain in children with cerebral palsy undergoing recurrent
botulinum toxin injections- A quasi-randomized controlled crossover study.
AB - OBJECTIVE: We investigated the impact of clown-care on pain in 45 children with
cerebral palsy who underwent recurrent Botulinum-toxin injections (age 7.04+/-
4.68 years). Participants were randomized to receive either clown (n = 20) or
standard (n = 25) -care. METHODS: Pain Visual-Analogue-Scale (range 1-5) was
reported before and after procedures. Pain assessment was lower for children
undergoing Botulinum-toxin injections with clown-care (2.89+/- 1.36) compared to
standard-care (3.85+/- 1.39; p = 0.036) even though pain anticipated prior to
procedures was similar (~3). FINDINGS: Children who underwent the first procedure
with clown-care reported lower pain even after they crossed-over to the following
procedure which was standard (p = 0.048). Carryover effect was more prominent in
injection-naive children (p = 0.019) and during multiple procedures (p = 0.009).
Prior pain experience correlated with pain in subsequent procedures only when
first experience was standard-care (p = 0.001). CONCLUSIONS: Clown-care
alleviated pain sensation during Botulinum-toxin injections and initial clown
care experience reduced pain during subsequent injections even though clowns were
not present. TRIAL REGISTRATION: clinicaltrials.gov ID # NCT01377883.
PMID- 28414729
TI - An evaluation of mental workload with frontal EEG.
AB - Using a wireless single channel EEG device, we investigated the feasibility of
using short-term frontal EEG as a means to evaluate the dynamic changes of mental
workload. Frontal EEG signals were recorded from twenty healthy subjects
performing four cognitive and motor tasks, including arithmetic operation, finger
tapping, mental rotation and lexical decision task. Our findings revealed that
theta activity is the common EEG feature that increases with difficulty across
four tasks. Meanwhile, with a short-time analysis window, the level of mental
workload could be classified from EEG features with 65%-75% accuracy across
subjects using a SVM model. These findings suggest that frontal EEG could be used
for evaluating the dynamic changes of mental workload.
PMID- 28414730
TI - Elements including metals in the atomizer and aerosol of disposable electronic
cigarettes and electronic hookahs.
AB - OBJECTIVE: Our purpose was to quantify 36 inorganic chemical elements in aerosols
from disposable electronic cigarettes (ECs) and electronic hookahs (EHs), examine
the effect of puffing topography on elements in aerosols, and identify the source
of the elements. METHODS: Thirty-six inorganic chemical elements and their
concentrations in EC/EH aerosols were determined using inductively coupled plasma
optical emission spectroscopy, and their source was identified by analyzing
disassembled atomizers using scanning electron microscopy and energy dispersive X
ray spectroscopy. RESULTS: Of 36 elements screened, 35 were detected in EC/EH
aerosols, while only 15 were detected in conventional tobacco smoke. Some
elements/metals were present in significantly higher concentrations in EC/EH
aerosol than in cigarette smoke. Concentrations of particular elements/metals
within EC/EH brands were sometimes variable. Aerosols generated at low and high
air-flow rates produced the same pattern of elements, although the total element
concentration decreased at the higher air flow rate. The relative amount of
elements in the first and last 60 puffs was generally different. Silicon was the
dominant element in aerosols from all EC/EH brands and in cigarette smoke. The
elements appeared to come from the filament (nickel, chromium), thick wire
(copper coated with silver), brass clamp (copper, zinc), solder joints (tin,
lead), and wick and sheath (silicon, oxygen, calcium, magnesium, aluminum). Lead
was identified in the solder and aerosol of two brands of EHs (up to 0.165 MUg/10
puffs). CONCLUSION: These data show that EC/EH aerosols contain a mixture of
elements, including heavy metals, with concentrations often significantly higher
than in conventional cigarette smoke. While the health effects of inhaling
mixtures of heated metals is currently not known, these data will be valuable in
future risk assessments involving EC/EH elements/metals.
PMID- 28414731
TI - A hyper-temporal remote sensing protocol for high-resolution mapping of
ecological sites.
AB - Ecological site classification has emerged as a highly effective land management
framework, but its utility at a regional scale has been limited due to the
spatial ambiguity of ecological site locations in the U.S. or the absence of
ecological site maps in other regions of the world. In response to these
shortcomings, this study evaluated the use of hyper-temporal remote sensing
(i.e., hundreds of images) for high spatial resolution mapping of ecological
sites. We posit that hyper-temporal remote sensing can provide novel insights
into the spatial variability of ecological sites by quantifying the temporal
response of land surface spectral properties. This temporal response provides a
spectral 'fingerprint' of the soil-vegetation-climate relationship which is
central to the concept of ecological sites. Consequently, the main objective of
this study was to predict the spatial distribution of ecological sites in a semi
arid rangeland using a 28-year time series of normalized difference vegetation
index from Landsat TM 5 data and modeled using support vector machine
classification. Results from this study show that support vector machine
classification using hyper-temporal remote sensing imagery was effective in
modeling ecological site classes, with a 62% correct classification. These
results were compared to Gridded Soil Survey Geographic database and expert
delineated maps of ecological sites which had a 51 and 89% correct
classification, respectively. An analysis of the effects of ecological state on
ecological site misclassifications revealed that sites in degraded states (e.g.,
shrub-dominated/shrubland and bare/annuals) had a higher rate of
misclassification due to their close spectral similarity with other ecological
sites. This study identified three important factors that need to be addressed to
improve future model predictions: 1) sampling designs need to fully represent the
range of both within class (i.e., states) and between class (i.e., ecological
sites) spectral variability through time, 2) field sampling protocols that
accurately characterize key soil properties (e.g., texture, depth) need to be
adopted, and 3) additional environmental covariates (e.g. terrain attributes)
need to be evaluated that may help further differentiate sites with similar
spectral signals. Finally, the proposed hyper-temporal remote sensing framework
may provide a standardized approach to evaluate and test our ecological site
concepts through examining differences in vegetation dynamics in response to
climatic variability and other drivers of land-use change. Results from this
study demonstrate the efficacy of the hyper-temporal remote sensing approach for
high resolution mapping of ecological sites, and highlights its utility in terms
of reduced cost and time investment relative to traditional manual mapping
approaches.
PMID- 28414732
TI - Active transforming growth factor-beta2 in the aqueous humor of posterior
polymorphous corneal dystrophy patients.
AB - PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is characterized by
abnormal proliferation of corneal endothelial cells. It was shown that TGF-beta2
present in aqueous humor (AH) could help maintaining the corneal endothelium in a
G1-phase-arrest state. We wanted to determine whether the levels of this protein
are changed in AH of PPCD patients. METHODS: We determined the concentrations of
active TGF-beta2 in the AH of 29 PPCD patients (42 samples) and 40 cadaver
controls (44 samples) by ELISA. For data analysis the PPCD patients were divided
based on either the molecular genetic cause of their disease as PPCD1 (37
samples), PPCD3 (1 sample) and PPCDx (not linked to a known PPCD loci, 4 samples)
or on the presence (17 samples) or absence (25 samples) of secondary glaucoma or
on whether they had undergone penetrating keratoplasty (PK, 32 samples) or
repeated PK (rePK, 7 samples). RESULTS: The level of active TGF-beta2 in the AH
of all PPCD patients (mean +/- SD; 386.98 +/- 114.88 pg/ml) in comparison to the
control group (260.95 +/- 112.43 pg/ml) was significantly higher (P = 0.0001).
Compared to the control group, a significantly higher level of active TGF-beta2
was found in the PPCD1 (P = 0.0005) and PPCDx (P = 0.0022) groups. Among patients
the levels of active TGF-beta2 were not significantly affected by gender, age,
secondary glaucoma or by the progression of dystrophy when one or repeated PK
were performed. CONCLUSION: The levels of active TGF-beta2 in the AH of PPCD
patients are significantly higher than control values, and thus the increased
levels of TGF-beta2 could be a consequence of the PPCD phenotype and can be
considered as another feature characterizing this disease.
PMID- 28414733
TI - Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique
approach and systematic review.
AB - INTRODUCTION: Antibodies targeting the inward-rectifying potassium channel KIR4.1
have been associated with multiple sclerosis (MS) but studies using diverse
techniques have failed to replicate this association. The detection of these
antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse
technical approaches may account for the disparity of results. We aimed to
replicate the association using three different approaches to overcome the
technical limitations of a single technique. We also performed a systematic
review to examine the association of anti-KIR4.1 antibodies with MS. METHODS:
Serum samples from patients with MS (n = 108) and controls (n = 77) were tested
for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with
the low-glycosylated fraction of recombinant KIR4.1 purified from transfected
HEK293 cells according to original protocols; 2) by immunocytochemistry using
KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.
transfected MO3.13 oligodendrocyte cell line. We developed a systematic review
and meta-analysis of the association of anti-KIR4.1 antibodies with MS according
to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines. RESULTS: We did not detect anti-KIR4.1 antibodies in the MS
patients or in controls using ELISA. Neither did we detect any significant
reactivity against the antigen on the cell surface using the KIR4.1-transfected
HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective
controlled studies in the systematic review. Only three studies showed a positive
association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity
between studies precluded meta-analysis of their results. CONCLUSION: We found no
association between anti-KIR4.1 antibody positivity and MS. Although this lack of
replication may be due to technical limitations, evidence from our study and
others is mounting against the role of KIR4.1 as a relevant MS autoantigen.
PMID- 28414735
TI - The coexistence of traditional medicine and biomedicine: A study with local
health experts in two Brazilian regions.
AB - This study investigated the combined use of traditional medicine and biomedicine
by local experts in Chapada do Araripe communities (Ceara State) and maroon
communities (Santa Catarina State), Brazil. The objective was to understand the
perception of local health specialists regarding the number of healers, demand
for healers and use of medicinal plants, and the dependence of different
environments to obtain such plants. We also aimed to understand the role of
medicinal plants to treat different categories of diseases and if there is a
complementary use of medicinal plants and allopathic biomedicine, according to
the context of each group. The research was conducted with local health
specialists that answered structured interviews, created free lists and
participated in guided tours to collect cited plants. Sixty-six local health
specialists were identified in the Araripe communities and 22 specialists in the
maroon communities. In the maroon communities, a greater number of specialists
thought there was a decrease in the number and demand for healers, as well as the
use of medicinal plants, due to changes in traditional livelihoods, since they
are located in a region where the effects of the modernization were more intense.
In the Chapada do Araripe communities the specialists knew more plants extracted
from native vegetation, whereas in the maroon communities cultivated plants were
better known, which may reflect the environmental conditions and the history of
each region. Medicinal plants are preferred to treat simpler health problems that
do not require medical care, such as gastrointestinal problems, general pain,
flues and colds. The biomedicine is used principally for problems with blood
pressure, general pains and endocrine and nutritional diseases. Even with the
particularities of each region, in general the use of medicinal plants and
biomedicines occurred in a complementary form in both regions; however, this
coexistence may result from these different contexts. This study also found that
there was knowledge and appreciation for traditional health practices in both
regions.
PMID- 28414734
TI - microRNAs as reference genes for quantitative PCR in cotton.
AB - Cotton (Gossypium hirsutum) is the most important non-food plant in the world.
Studies concerning the fiber quality and plant fitness of cotton at molecular
level depend on high sensitive and reproducible gene-expression assays. However,
only a few reports have described genes suitable for normalizing gene expression
data. In this study, we report for the first time that microRNAs (miRNAs) are
reliable reference genes (RGs) for cotton gene expression normalization in
quantitative real-time reverse transcription (RT)-PCR. The stability of cotton
miRNAs was assayed in root, stem, leaf and flower samples from three different
cultivars [FiberMax (FM966), Delta Opal (DO) and Cedro] and under conditions of
biotic stress caused by infection with Cotton leafroll dwarf virus (CLRDV). The
stability of mRNAs already described as reference genes in cotton was also
assessed. The geNorm, NormFinder, BestKeeper and DeltaCt algorithms were used to
select the best reference genes. In 8 of the 12 sets tested, miRNAs (miR172, 168
and 390) were found to be the best RGs. To validate the best selected RGs,
miR159, miR164, miR2118, miR2910, miR3476, GhDCL2 and GhDCL4 expression levels
were evaluated under biotic stress conditions, and miR164 and a putative myo
inositol oxigenase gene (GhMIOX) were assessed in leaves and flowers. The RGs
selected in this work proved to be excellent reference genes in the two cases
studied. Our results support the use of miRNAs as reference genes for miRNA and
protein-coding genes.
PMID- 28414736
TI - Catchment vegetation and temperature mediating trophic interactions and
production in plankton communities.
AB - Climatic factors influence the interactions among trophic levels in an ecosystem
in multiple ways. However, whereas most studies focus on single factors in
isolation, mainly due to interrelation and correlation among drivers complicating
interpretation and analyses, there are still only few studies on how multiple
ecosystems respond to climate related factors at the same time. Here, we use a
hierarchical Bayesian model with a bioenergetic predator-prey framework to study
how different climatic factors affect trophic interactions and production in
small Arctic lakes. Natural variation in temperature and catchment land-cover was
used as a natural experiment to exemplify how interactions between and production
of primary producers (phytoplankton) and grazers (zooplankton) are driven by
direct (temperature) and indirect (catchment vegetation) factors, as well as the
presence or absence of apex predators (fish). The results show that increased
vegetation cover increased phytoplankton growth rate by mediating lake nutrient
concentration. At the same time, increased temperature also increased grazing
rates by zooplankton. Presence of fish increased zooplankton mortality rates,
thus reducing grazing. The Arctic is currently experiencing an increase in both
temperature and shrub vegetation cover due to climate change, a trend, which is
likely to continue. Our results point towards a possible future general weakening
of zooplankton grazing on phytoplankton and greening of arctic lakes with
increasing temperatures. At the same time, the impact of the presence of an apex
predator indicate considerable local variation in the response. This makes
direction and strength of global change impacts difficult to forecast.
PMID- 28414737
TI - Peer norm guesses and self-reported attitudes towards performance-related pay.
AB - Due to a variety of reasons, people see themselves differently from how they see
others. This basic asymmetry has broad consequences. It leads people to judge
themselves and their own behavior differently from how they judge others and
others' behavior. This research, first, studies the perceptions and attitudes of
Greek Public Sector employees towards the introduction of Performance-Related Pay
(PRP) systems trying to reveal whether there is a divergence between individual
attitudes and guesses on peers' attitudes. Secondly, it is investigated whether
divergence between own self-reported and peer norm guesses could mediate the
acceptance of the aforementioned implementation once job status has been
controlled for. This study uses a unique questionnaire of 520 observations which
was designed to address the questions outlined in the preceding lines. Our
econometric results indicate that workers have heterogeneous attitudes and hold
heterogeneous beliefs on others' expectations regarding a successful
implementation of PRP. Specifically, individual perceptions are less skeptical
towards PRP than are beliefs on others' attitudes. Additionally, we found that
managers are significantly more optimistic than lower rank employees regarding
the expected success of PRP systems in their jobs. However, they both expect
their peers to be more negative than they themselves are.
PMID- 28414738
TI - Barriers and facilitators for men to attend prenatal care and obtain HIV
voluntary counseling and testing in Brazil.
AB - BACKGROUND: Providing HIV voluntary counseling and testing (VCT) to men who
attend their partner's prenatal care is an intervention with potential to reduce
HIV transmission to women and infants during the vulnerable period of pregnancy.
Little is known about the acceptability of this intervention in global settings
outside of Africa. METHODS: We conducted in-depth qualitative interviews to
evaluate potential barriers and facilitators to prenatal care attendance for HIV
VCT with 20 men who did and 15 men who did not attend prenatal care with their
partners at Hospital Conceicao in Porto Alegre, Brazil. Men were recruited at the
labor and delivery unit at Hospital Conceicao via a scripted invitation while
visiting their newborn infant. Interviews lasted from 35-55 minutes and were
conducted in Portuguese by a local resident trained extensively in qualitative
methods. All interviews were transcribed verbatim, translated, and then analyzed
using Atlast.ti software. An analysis of themes was then conducted using direct
quotes and statements. We applied and adapted the AIDS Risk Reduction Theoretical
Model and HIV Testing Decisions Model to the qualitative data to identify themes
in the 35 interviews. RESULTS: If offered HIV testing during prenatal care, all
men in both groups stated they would accept this intervention. Yet, individual,
relationship and systemic factors were identified that affect these Brazilian
men's decision to attend prenatal care, informing our final conceptual model. The
men interviewed had a general understanding of the value of HIV prevention of
mother to child transmission. They also described open and communicative
relationships with their significant others and displayed a high level of
enthusiasm towards optimizing the health of their expanding family. The major
barriers to attending prenatal care included perceived stigma against HIV
infected individuals, men's lack of involvement in planning of the pregnancy as
well as inconvenient scheduling of prenatal care, due to conflicting work
schedules. CONCLUSIONS: Brazilian men displayed high levels of HIV-related
knowledge as well as open communication about HIV testing; especially when
compared to findings from African studies. Future efforts should reorient
prenatal care towards providing care to the entire family with a clear focus on
protecting the infant from preventable diseases. Formally inviting men to
prenatal care and providing them an acceptable medical excuse from work may
enhance male involvement.
PMID- 28414740
TI - Cryopreserved human aortic root allografts arterial wall: Structural changes
occurring during thawing.
AB - BACKGROUND: The aim of our experimental work was to assess morphological changes
of arterial wall that arise during different thawing protocols of a cryopreserved
human aortic root allograft (CHARA) arterial wall. METHODS: The experiment was
performed on CHARAs. Two thawing protocols were tested: 1, CHARAs were thawed at
a room temperature at +23 degrees C; 2, CHARAs were placed directly into a water
bath at +37 degrees C. MICROSCOPIC SAMPLES PREPARATION: After fixation, all
samples were washed in distilled water for 5 min, and dehydrated in a graded
ethanol series (70, 85, 95, and 100%) for 5 min at each level. The tissue samples
were then immersed in 100% hexamethyldisilazane for 10 minutes and air dried in
an exhaust hood at room temperature. Processed samples were mounted on stainless
steel stubs, coated with gold. RESULTS: Thawing protocol 1: All 6 (100%) samples
showed loss of the endothelium and damage to the subendothelial layers with
randomly dispersed circular defects and micro-fractures without smooth muscle
cells contractions in the tunica media. Thawing protocol 2: All 6 (100%) samples
showed loss of endothelium from the luminal surface, longitudinal corrugations in
the direction of blood flow caused by smooth muscle cells contractions in the
tunica media with frequent fractures in the subendothelial layer. CONCLUSION: All
the samples thawed at the room temperature showed smaller structural damage to
the CHARA arterial wall with no smooth muscle cell contraction in tunica media
when compared to the samples thawed in a water bath.
PMID- 28414739
TI - An in silico pan-genomic probe for the molecular traits behind Lactobacillus
ruminis gut autochthony.
AB - As an ecological niche, the mammalian intestine provides the ideal habitat for a
variety of bacterial microorganisms. Purportedly, some commensal genera and
species offer a beneficial mix of metabolic, protective, and structural processes
that help sustain the natural digestive health of the host. Among these sort of
gut inhabitants is the Gram-positive lactic acid bacterium Lactobacillus ruminis,
a strict anaerobe with both pili and flagella on its cell surface, but also known
for being autochthonous (indigenous) to the intestinal environment. Given that
the molecular basis of gut autochthony for this species is largely unexplored and
unknown, we undertook a study at the genome level to pinpoint some of the
adaptive traits behind its colonization behavior. In our pan-genomic probe of L.
ruminis, the genomes of nine different strains isolated from human, bovine,
porcine, and equine host guts were compiled and compared for in silico analysis.
For this, we conducted a geno-phenotypic assessment of protein-coding genes, with
an emphasis on those products involved with cell-surface morphology and anaerobic
fermentation and respiration. We also categorized and examined the core and
accessory genes that define the L. ruminis species and its strains. Here, we made
an attempt to identify those genes having ecologically relevant phenotypes that
might support or bring about intestinal indigenousness.
PMID- 28414741
TI - Effects of music on arousal during imagery in elite shooters: A pilot study.
AB - Beneficial effects of music on several performance-related aspects of sport have
been reported, but the processes involved are not well understood. The purpose of
the present study was to investigate effects of relaxing and arousing classical
music on physiological indicators and subjective perceptions of arousal during
imagery of a sport task. First, appropriate music excerpts were selected. Then,
12 skilled shooters performed shooting imagery while listening to the three
preselected music excerpts in randomized order. Participants' galvanic skin
response, peripheral temperature, and electromyography were monitored during
music played concurrently with imagery. Subjective music ratings and
physiological measures showed, as hypothesized, that unfamiliar relaxing music
was the most relaxing and unfamiliar arousing music was the most arousing.
Researchers should examine the impact of unfamiliar relaxing and arousing music
played during imagery on subsequent performance in diverse sports. Practitioners
can apply unfamiliar relaxing and arousing music with imagery to manipulate
arousal level.
PMID- 28414742
TI - To electrify bilingualism: Electrophysiological insights into bilingual metaphor
comprehension.
AB - Though metaphoric language comprehension has previously been investigated with
event-related potentials, little attention has been devoted to extending this
research from the monolingual to the bilingual context. In the current study,
late proficient unbalanced Polish (L1)-English (L2) bilinguals performed a
semantic decision task to novel metaphoric, conventional metaphoric, literal, and
anomalous word pairs presented in L1 and L2. The results showed more pronounced
P200 amplitudes to L2 than L1, which can be accounted for by differences in the
subjective frequency of the native and non-native lexical items. Within the early
N400 time window (300-400 ms), L2 word dyads evoked delayed and attenuated
amplitudes relative to L1 word pairs, possibly indicating extended lexical search
during foreign language processing, and weaker semantic interconnectivity for L2
compared to L1 words within the memory system. The effect of utterance type was
observed within the late N400 time window (400-500 ms), with smallest amplitudes
evoked by literal, followed by conventional metaphoric, novel metaphoric, and
anomalous word dyads. Such findings are interpreted as reflecting more resource
intensive cognitive mechanisms governing novel compared to conventional metaphor
comprehension in both the native and non-native language. Within the late
positivity time window (500-800 ms), Polish novel metaphors evoked reduced
amplitudes relative to literal utterances. In English, on the other hand, this
effect was observed for both novel and conventional metaphoric word dyads. This
finding might indicate continued effort in information retrieval or access to the
non-literal route during novel metaphor comprehension in L1, and during novel and
conventional metaphor comprehension in L2. Altogether, the present results point
to decreased automaticity of cognitive mechanisms engaged in non-native and non
dominant language processing, and suggest a decreased sensitivity to the levels
of conventionality of metaphoric meanings in late proficient unbalanced bilingual
speakers.
PMID- 28414743
TI - The ET-1-mediated carbonylation and degradation of ANXA1 induce inflammatory
phenotype and proliferation of pulmonary artery smooth muscle cells in HPS.
AB - Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver
disease, which markedly increases mortality. Pulmonary vascular remodelling (PVR)
induced by circulating mediators plays an important role in the pathogenesis of
HPS, while the underlying mechanism remains undefined. In the present study, we
reported that endothelin-1 (ET-1) is up-regulated and annexin A1(ANXA1) is down
regulated in HPS rat, and ET-1 decreases the ANXA1 expression in a dose-dependent
manner in rat pulmonary arterial smooth muscle cells (PASMCs). Then, we showed
that ANXA1 can decrease nuclear p-ERK1/2 accumulation and decrease the cyclin D1
expression, thus resulting in the subsequent inhibition of PASMCs proliferation.
As previously reported, we confirmed that ET-1 decreases the ANXA1 protein levels
by the carbonylation and degradation of ANXA1. In conclusion, our research links
the signaling cascade of ET1-ANXA1-cell proliferation to a potential therapeutic
strategy for blocking IPS-associated PVR.
PMID- 28414744
TI - Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in
the visceral leishmaniasis vector Phlebotomus argentipes.
AB - BACKGROUND: Indoor residual spraying (IRS) with DDT has been the primary strategy
for control of the visceral leishmaniasis (VL) vector Phlebotomus argentipes in
India but efficacy may be compromised by resistance. Synthetic pyrethroids are
now being introduced for IRS, but with a shared target site, the para voltage
gated sodium channel (VGSC), mutations affecting both insecticide classes could
provide cross-resistance and represent a threat to sustainable IRS-based disease
control. METHODOLOGY/PRINCIPAL FINDINGS: A region of the Vgsc gene was sequenced
in P. argentipes from the VL hotspot of Bihar, India. Two knockdown resistance
(kdr) mutations were detected at codon 1014 (L1014F and L1014S), each common in
mosquitoes, but previously unknown in phlebotomines. Both kdr mutations appear
largely recessive, but as homozygotes (especially 1014F/F) or as 1014F/S
heterozygotes exert a strong effect on DDT resistance, and significantly predict
survivorship to class II pyrethroids in short-duration bioassays. The mutations
are present at high frequency in wild P. argentipes populations from Bihar, with
1014F significantly more common in higher VL areas. CONCLUSIONS/SIGNIFICANCE: The
Vgsc mutations detected appear to be a primary mechanism underlying DDT
resistance in P. argentipes and a contributory factor in reduced pyrethroid
susceptibility, suggesting a potential impact if P. argentipes are subjected to
suboptimal levels of pyrethroid exposure, or additional resistance mechanisms
evolve. The assays to detect kdr frequency changes provide a sensitive, high
throughput monitoring tool to detecting spatial and temporal variation in
resistance in P. argentipes.
PMID- 28414745
TI - Mapping the SRS-22r questionnaire onto the EQ-5D-5L utility score in patients
with adolescent idiopathic scoliosis.
AB - This is a prospective study to establish prediction models that map the refined
Scoliosis Research Society 22-item (SRS-22r) onto EuroQoL-5 dimension 5-level (EQ
5D-5L) utility scores in adolescent idiopathic scoliosis (AIS) patients.
Comparison of treatment outcomes in AIS can be determined by cost-utility
analysis. However, the mainstay spine-specific health-related quality of life
outcome measure, the SRS-22r questionnaire does not provide utility assessment.
In this study, AIS patients were prospectively recruited to complete both the EQ
5D-5L and SRS-22r questionnaires by trained interviewers. Ordinary least squares
regression was undertaken to develop mapping models, which the validity and
robustness were assessed by using the 10-fold cross-validation procedure. EQ-5D
5L utility scores were regressed on demographics, Cobb angle, curve types,
treatment modalities, and five domains of the SRS-22r questionnaire. Three models
were developed using stepwise selection method. EQ-5D-5L scores were regressed on
1) main effects of SRS-22r subscale scores, 2) as per 1 plus squared and
interaction terms, and 3) as per 2 plus demographic and clinical characteristics.
Model goodness-of-fit was assessed using R-square, adjusted R-square, and
information criteria; whereas the predictive performance was evaluated using root
mean square error (RMSE), mean absolute error (MAE), and the proportion of
absolute error within the threshold of 0.05 and 0.10. A total of 227 AIS patients
with mean age of 15.6 years were recruited. The EQ-5D-5L scores were predicted by
four domains of SRS-22r (main effects of 'Function', 'Pain', 'Appearance' and
'Mental Health', and squared term of 'Function' and 'Pain'), and Cobb angle in
Model 3 with the best goodness-of-fit (R-square/adjusted R-square: 62.1%/60.9%).
Three models demonstrated an acceptance predictive performance in error analysis
applying 10-fold cross-validation to three models where RMSE and MAE were between
0.063-0.065 and between 0.039-0.044, respectively. Model 3 was therefore
recommended out of three mapping models established in this paper. To our
knowledge, this is the first study to map a spine-specific health-related quality
of life measure onto EQ-5D-5L for AIS patients. With the consideration and
incorporation of demographic and clinical characteristics, over 60% variance
explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L
utility scores from existing SRS-22r data for health economic appraisal of
different treatment options.
PMID- 28414746
TI - Local Th17/IgA immunity correlate with protection against intranasal infection
with Streptococcus pyogenes.
AB - Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide
array of infections. Respiratory transmission via droplets is the most common
mode of transmission but it may also infect the host via other routes such as
lesions in the skin. To advance the development of a future vaccine against GAS,
it is therefore important to investigate how protective immunity is related to
the route of vaccine administration. To explore this, we examined whether a
parenterally administered anti-GAS vaccine could protect against an intranasal
GAS infection or if this would require locally primed immunity. We foundd that a
parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal
infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently
protected against an intraperitoneal GAS infection. However, the same vaccine
administered via the intranasal route was able to induce protection against
repeated intranasal GAS infections in a murine challenge model. The lack of
intranasal protection induced by the parenteral vaccine correlated with a reduced
mucosal recall response at the site of infection. Taken together, our results
demonstrate that locally primed immunity is important for the defense against
intranasal infection with Streptococcus pyogenes.
PMID- 28414747
TI - Hierarchical and coupling model of factors influencing vessel traffic flow.
AB - Understanding the characteristics of vessel traffic flow is crucial in
maintaining navigation safety, efficiency, and overall waterway transportation
management. Factors influencing vessel traffic flow possess diverse features such
as hierarchy, uncertainty, nonlinearity, complexity, and interdependency. To
reveal the impact mechanism of the factors influencing vessel traffic flow, a
hierarchical model and a coupling model are proposed in this study based on the
interpretative structural modeling method. The hierarchical model explains the
hierarchies and relationships of the factors using a graph. The coupling model
provides a quantitative method that explores interaction effects of factors using
a coupling coefficient. The coupling coefficient is obtained by determining the
quantitative indicators of the factors and their weights. Thereafter, the data
obtained from Port of Tianjin is used to verify the proposed coupling model. The
results show that the hierarchical model of the factors influencing vessel
traffic flow can explain the level, structure, and interaction effect of the
factors; the coupling model is efficient in analyzing factors influencing traffic
volumes. The proposed method can be used for analyzing increases in vessel
traffic flow in waterway transportation system.
PMID- 28414748
TI - Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA
nephropathy.
AB - Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in
the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is
appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b
staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in
assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown.
Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou
University and Peking University First Hospital diagnosed with IgAN in CKD stage
3 were enrolled and successfully followed up. Cox proportional hazards model was
used to analyze hazard ratios of reaching the composite endpoints (doubling of
serum creatinine, end-stage renal disease: estimated glomerular filtration rate
(eGFR) <15 ml/min/per 1.73 m2 or renal replacement therapy, or death) for
patients with different eGFR and risk factors affecting composite endpoints. The
Kaplan-Meier method was used to calculate the cumulative renal survival rate of
patients. When eGFR was lower than 45 ml/min/per 1.73 m2, the hazard ratio
increased sharply for patients in CKD stage 3 who reached the composite
endpoints. Renal injury and prognosis were significantly different between
patients in the G3a and G3b groups. Stage G3b was a major risk factor affecting
prognosis. A threshold value of 45 ml/min/per 1.73 m2 appears appropriate to
assess the prognosis of IgAN patients with CKD stage 3. Dividing IgAN patients
with CKD stage 3 into G3a and G3b is very useful to help understand disease
conditions and for predicting the risk for disease progression.
PMID- 28414749
TI - Sequence variability of the respiratory syncytial virus (RSV) fusion gene among
contemporary and historical genotypes of RSV/A and RSV/B.
AB - BACKGROUND: The fusion (F) protein of RSV is the major vaccine target. This
protein undergoes a conformational change from pre-fusion to post-fusion. Both
conformations share antigenic sites II and IV. Pre-fusion F has unique antigenic
sites p27, o, alpha2alpha3beta3beta4, and MPE8; whereas, post-fusion F has unique
antigenic site I. Our objective was to determine the antigenic variability for
RSV/A and RSV/B isolates from contemporary and historical genotypes compared to a
historical RSV/A strain. METHODS: The F sequences of isolates from GenBank,
Houston, and Chile (N = 1,090) were used for this analysis. Sequences were
compared pair-wise to a reference sequence, a historical RSV/A Long strain.
Variability (calculated as %) was defined as changes at each amino acid (aa)
position when compared to the reference sequence. Only aa at antigenic sites with
variability >=5% were reported. RESULTS: A total of 1,090 sequences (822 RSV/A
and 268 RSV/B) were analyzed. When compared to the reference F, those domains
with the greatest number of non-synonymous changes included the signal peptide,
p27, heptad repeat domain 2, antigenic site o, and the transmembrane domain.
RSV/A subgroup had 7 aa changes in the antigenic sites: site I (N = 1), II (N =
1), p27 (N = 4), alpha2alpha3beta3beta4(AM14) (N = 1), ranging in frequency from
7-91%. In comparison, RSV/B had 19 aa changes in antigenic sites: I (N = 3), II
(N = 1), p27 (N = 9), o (N = 4), alpha2alpha3beta3beta4(AM14) (N = 1), and MPE8
(N = 1), ranging in frequency from 79-100%. DISCUSSION: Although antigenic sites
of RSV F are generally well conserved, differences are observed when comparing
the two subgroups to the reference RSV/A Long strain. Further, these
discrepancies are accented in the antigenic sites in pre-fusion F of RSV/B
isolates, often occurring with a frequency of 100%. This could be of importance
if a monovalent F protein from the historical GA1 genotype of RSV/A is used for
vaccine development.
PMID- 28414751
TI - The influence of journal submission guidelines on authors' reporting of
statistics and use of open research practices.
AB - From January 2014, Psychological Science introduced new submission guidelines
that encouraged the use of effect sizes, estimation, and meta-analysis (the "new
statistics"), required extra detail of methods, and offered badges for use of
open science practices. We investigated the use of these practices in empirical
articles published by Psychological Science and, for comparison, by the Journal
of Experimental Psychology: General, during the period of January 2013 to
December 2015. The use of null hypothesis significance testing (NHST) was
extremely high at all times and in both journals. In Psychological Science, the
use of confidence intervals increased markedly overall, from 28% of articles in
2013 to 70% in 2015, as did the availability of open data (3 to 39%) and open
materials (7 to 31%). The other journal showed smaller or much smaller changes.
Our findings suggest that journal-specific submission guidelines may encourage
desirable changes in authors' practices.
PMID- 28414750
TI - Effect of transcription factor resource sharing on gene expression noise.
AB - Gene expression is intrinsically a stochastic (noisy) process with important
implications for cellular functions. Deciphering the underlying mechanisms of
gene expression noise remains one of the key challenges of regulatory biology.
Theoretical models of transcription often incorporate the kinetics of how
transcription factors (TFs) interact with a single promoter to impact gene
expression noise. However, inside single cells multiple identical gene copies as
well as additional binding sites can compete for a limiting pool of TFs. Here we
develop a simple kinetic model of transcription, which explicitly incorporates
this interplay between TF copy number and its binding sites. We show that TF
sharing enhances noise in mRNA distribution across an isogenic population of
cells. Moreover, when a single gene copy shares it's TFs with multiple competitor
sites, the mRNA variance as a function of the mean remains unaltered by their
presence. Hence, all the data for variance as a function of mean expression
collapse onto a single master curve independent of the strength and number of
competitor sites. However, this result does not hold true when the competition
stems from multiple copies of the same gene. Therefore, although previous studies
showed that the mean expression follows a universal master curve, our findings
suggest that different scenarios of competition bear distinct signatures at the
level of variance. Intriguingly, the introduction of competitor sites can
transform a unimodal mRNA distribution into a multimodal distribution. These
results demonstrate the impact of limited availability of TF resource on the
regulation of noise in gene expression.
PMID- 28414752
TI - An angiogenesis platform using a cubic artificial eggshell with patterned blood
vessels on chicken chorioallantoic membrane.
AB - The chorioallantoic membrane (CAM) containing tiny blood vessels is an
alternative to large animals for studies involving angiogenesis and tissue
engineering. However, there is no technique to design the direction of growing
blood vessels on the CAM at the microscale level for tissue engineering
experiments. Here, a methodology is provided to direct blood vessel formation on
the surface of a three-dimensional egg yolk using a cubic artificial eggshell
with six functionalized membranes. A structure on the lateral side of the
eggshell containing a straight channel and an interlinked chamber was designed,
and the direction and formation area of blood vessels with blood flow was
artfully defined by channels with widths of 70-2000 MUm, without sharply reducing
embryo viability. The relationship between the size of interlinked chamber and
the induction of blood vessels was investigated to establish a theory of design.
Role of negative and positive pressure in the induction of CAM with blood vessels
was investigated, and air pressure change in the culture chamber was measured to
demonstrate the mechanism for blood vessel induction. Histological evaluation
showed that components of CAM including chorionic membrane and blood vessels were
induced into the channels. Based on our design theory, blood vessels were induced
into arrayed channels, and channel-specific injection and screening were
realized, which demonstrated proposed applications. The platform with position-
and space-controlled blood vessels is therefore a powerful tool for biomedical
research, which may afford exciting applications in studies involved in local
stimulation of blood vessel networks and those necessary to establish a living
system with blood flow from a beating heart.
PMID- 28414753
TI - Sustained low peritoneal effluent CCL18 levels are associated with preservation
of peritoneal membrane function in peritoneal dialysis.
AB - Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal
sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications.
Combining clinical and peritoneal transport data with the measurement of
molecular biomarkers, such as the chemokine CCL18, would improve the complex
diagnosis and management of PMF. We measured CCL18 levels in 43 patients'
effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by
retrospective longitudinal study, and evaluated their association with PMF/EPS
development and peritoneal risk factors. To confirm the trends observed in the
longitudinal study, a cross-sectional study was performed on 61 isolated samples
from long-term (more than 3 years) patients treated with PD. We observed that the
patients with no membrane dysfunction showed sustained low CCL18 levels in
peritoneal effluent over time. An increase in CCL18 levels at any time was
predictive of PMF development (final CCL18 increase over baseline, p = .014; and
maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent
under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels
were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067).
Moreover, CCL18 levels in effluent at year 3 of PD were independently associated
with a risk of PMF development, adjusted for the classical (water and creatinine)
peritoneal transport parameters. These trends were confirmed in a cross-sectional
study of 61 long-term patients treated with PD. In conclusion, our study shows
the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to
predict PMF and suggests CCL18 as a new marker and mediator of this serious
condition as well as a new potential therapeutic target.
PMID- 28414754
TI - Type 2 diabetes, depressive symptoms and trajectories of cognitive decline in a
national sample of community-dwellers: A prospective cohort study.
AB - We examined the individual and synergistic effects of type 2 diabetes and
elevated depressive symptoms on memory and executive function trajectories over
10 and eight years of follow-up, respectively. Our sample comprised 10,524
community-dwellers aged >=50 years in 2002-03 from the English Longitudinal Study
of Ageing. With respect to memory (word recall), participants with either
diabetes or elevated depressive symptoms recalled significantly fewer words
compared with those free of these conditions (reference category), but more words
compared with those with both conditions. There was a significant acceleration in
the rate of memory decline in participants aged 50-64 years with both conditions
(-0.27, 95% CI, -0.45 to -0.08, per study wave), which was not observed in those
with either condition or aged >=65 years. With respect to executive function
(animal naming), participants aged >=65 years with diabetes or those with
elevated depressive symptoms named significantly fewer animals compared with the
reference category, while those with both conditions named fewer animals compared
with any other category. The rate of executive function decline was significantly
greater in participants with both conditions (-0.54, 95% CI, -0.99 to -0.10; and
0.71, 95% CI, -1.16 to -0.27, per study wave, for those aged 50-64 and >=65
years, respectively), but not in participants with either condition. Diabetes and
elevated depressive symptoms are inversely associated with memory and executive
function, but, individually, do not accelerate cognitive decline. The co
occurrence of diabetes and elevated depressive symptoms significantly accelerates
cognitive decline over time, especially among those aged 50-64 years.
PMID- 28414755
TI - Childhood socioeconomic status and childhood maltreatment: Distinct associations
with brain structure.
AB - The present study examined the relationship between childhood socioeconomic
status (SES), childhood maltreatment, and the volumes of the hippocampus and
amygdala between the ages of 25 and 36 years. Previous work has linked both low
SES and maltreatment with reduced hippocampal volume in childhood, an effect
attributed to childhood stress. In 46 adult subjects, only childhood
maltreatment, and not childhood SES, predicted hippocampal volume in regression
analyses, with greater maltreatment associated with lower volume. Neither factor
was related to amygdala volume. When current SES and recent interpersonal
stressful events were also considered, recent interpersonal stressful events
predicted smaller hippocampal volumes over and above childhood maltreatment.
Finally, exploratory analyses revealed a significant sex by childhood SES
interaction, with women's childhood SES showing a significantly more positive
relation (less negative) with hippocampus volume than men's. The overall effect
of childhood maltreatment but not SES, and the sex-specific effect of childhood
SES, indicate that different forms of stressful childhood adversity affect brain
development differently.
PMID- 28414756
TI - Reduction in the copy number and expression level of the recurrent human
papillomavirus integration gene fragile histidine triad (FHIT) predicts the
transition of cervical lesions.
AB - Cervical cancer is the second most common cancer and the third leading cause of
cancer death in females worldwide, especially in developing countries. High risk
human papillomavirus (HR-HPV) infection causes cervical cancer and precancerous
cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into
the host chromatin is an important step in cervical carcinogenesis. The detection
of integrated papillomavirus sequences-PCR (DIPS-PCR) allowed us to explore HPV
integration in the human genome and to determine the pattern of this integration.
We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and
40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the
clinical samples and the HeLa and SiHa cell lines. Among all the integration
loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1
(2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To
further explore the effect of HR-HPV integration in the 3p14.2 locus, we used
fluorescence in situ hybridization (FISH) to determine the copy number of the
3p14.2 locus and immunohistochemistry (IHC) to determine the protein expression
levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus
copy number and FHIT protein expression levels showed significant decreases when
CIN transitioned to cervical cancer. HPV copy number was also evaluated in these
clinical samples, and the copy number of HPV increased significantly between CIN
and cervical cancer samples. Finally, we employed receiver operating
characteristic curve (ROC curve) analysis to evaluate the potential of all these
indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT
copy number and FHIT protein expression levels have good diagnostic efficiencies.
PMID- 28414757
TI - Predictors of smoking among primary and secondary school students in Botswana.
AB - This study seeks to determine the prevalence and risk factors for smoking among
students aged 12-18 years in two cities in Botswana. Using a sample of 2554
students we adapted the Global Youth Tobacco Survey (GYTS) methodology to assess
students' smoking practices, knowledge, beliefs and attitudes. Logistic
regression models were used to evaluate factors associated with smoking. The
results revealed that 10% of students were current tobacco smokers with 29%
reporting having tried smoking. Self-image and acceptance by peers were the
strongest predictors of smoking overall (adjusted Odds Ratio [aOR]: 3.13, 95%,
Confidence Interval [CI]: 2.67-3.66). Intention to smoke or to continue to smoke
and perceived norms in conformity with smoking were also independently associated
with smoking (aOR: 1.81, 95% CI: 167-2.11 and aOR: 1.31, 95% CI: 1.10-1.57,
respectively). Perceived prevalence and exposure to smoking by peers and family
and access to tobacco products was stronger among females (aOR: 1.69, 95% CI:
1.52-1.91) compared to males (aOR: 0.93, 95% CI: 0.70-1.24). Our results indicate
that anti-tobacco interventions in Botswana should prioritize intra-personal
factors associated with smoking. Our findings also suggest that different
interventions targeting male and female students should be explored.
PMID- 28414758
TI - Early dialysis initiation does not improve clinical outcomes in elderly end-stage
renal disease patients: A multicenter prospective cohort study.
AB - BACKGROUND: The optimal timing for initiating dialysis in end-stage renal disease
(ESRD) is controversial, especially in the elderly. METHODS: 665 patients >=65
years old who began dialysis from August 2008 to February 2015 were prospectively
enrolled in the Clinical Research Center for End-Stage Renal Disease cohort
study. Participants were divided into 2 groups based on the median estimated
glomerular filtration rate at the initiation of dialysis. Propensity score
matching (PSM) was used to compare the overall survival rate, cardiovascular
events, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) results,
Karnofsky performance scale values, Beck's depression inventory values, and
subjective global assessments. RESULTS: The mean patient age was 72.0 years, and
61.7% of the patients were male. Overall, the cumulative survival rates were
lower in the early initiation group, although the difference was not significant
after PSM. Additionally, the survival rates of the 2 groups did not differ after
adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin,
serum calcium and phosphorus levels. Although the early initiation group showed a
lower physical component summary score on the KDQOL-36 3 months after dialysis,
the difference in scores was not significant 12 months after dialysis.
Furthermore, the difference was not significant after PSM. The Karnofsky
performance scale, Beck's depression inventory, and subjective global assessments
were not significantly different 3 and 12 months after dialysis initiation.
CONCLUSIONS: The timing of dialysis initiation is not associated with clinical
outcomes in elderly patients with ESRD.
PMID- 28414760
TI - Real benefit of a protective factor against dementia: Importance of controlling
for death. Example of sport practice.
AB - OBJECTIVES: To analyse the impact of a risk factor on several epidemiological
indicators of death and dementia; the example of sport practice is presented.
METHODS: A population of 3670 non-demented subjects living at home and aged 65
and older from the PAQUID study were followed for 22 years. Sport practice was
documented at baseline. Dementia (according to DSM-III-R criteria) and death were
assessed at each visit. Analyses were performed with an Illness-Death model,
providing results on the risks of dementia and death, probabilities and life
expectancies. RESULTS: A total of 743 subjects (20.2%) participated in regular
sport practice. During the follow-up, the proportion of death was lower in the
elderly people practicing sport (EPPS), whereas the proportion of incident
dementia cases was the same. The adjusted model showed a decreased risk of
dementia (HR = 0.84 (0.72-1.00)) and of death for non-demented subjects (HR =
0.61 (0.51-0.71)) for EPPS but a similar risk of death with dementia in both
sport groups. The probability of remaining alive without dementia was higher in
EPPS, whereas the probability of dying was lower. The mean lifetime without
dementia was 3 years higher for the EPPS, but the mean lifetime with dementia was
the same. DISCUSSION: A preventive measure on a protective factor that is more
effective for preventing death than dementia could lead to an increased lifetime
without dementia; however, the number of demented cases may remain unchanged,
even if the risk of developing dementia is reduced. This dynamic is important to
forecast the need for health care and social services for the elderly.
PMID- 28414759
TI - Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant,
with coronary artery disease.
AB - BACKGROUND: The genetic architecture of coronary artery disease has not been
fully elucidated, especially in Asian countries. Moyamoya disease is a
progressive cerebrovascular disease that is reported to be complicated by
coronary artery disease. Because most Japanese patients with moyamoya disease
carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be
a risk factor for coronary artery disease; however, this possibility has never
been tested. METHODS AND RESULTS: We genotyped the RNF213 p.R4810K variant in 956
coronary artery disease patients and 716 controls and tested the association
between p.R4810K and coronary artery disease. We also validated the association
in an independent population of 311 coronary artery disease patients and 494
controls. In the replication study, the p.R4810K genotypes were imputed from
genome-wide genotyping data based on the 1000 Genomes Project. We used
multivariate logistic regression analyses to adjust for well-known risk factors
such as dyslipidemia and smoking habits. In the primary study population, the
frequency of the minor variant allele was significantly higher in patients with
coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of
2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the
association remained significant, with an odds ratio of 2.90 (95% confidence
interval: 1.37-6.61; p = 0.005). In the replication study, the association was
significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence
interval: 1.16-21.53; p = 0.031), although it did not reach statistical
significance when further adjusted for risk factors (odds ratio = 3.82; 95%
confidence interval: 0.87-16.77; p = 0.076). CONCLUSIONS: The RNF213 p.R4810K
variant appears to be significantly associated with coronary artery disease in
the Japanese population.
PMID- 28414761
TI - Identification of a plasma metabolomic signature of thrombotic myocardial
infarction that is distinct from non-thrombotic myocardial infarction and stable
coronary artery disease.
AB - AIMS: Current non-invasive diagnostics for acute myocardial infarction (MI)
identify myocardial necrosis rather than the primary cause and therapeutic target
plaque disruption and resultant thrombosis. The aim of this study was to identify
changes specific to plaque disruption and pathological thrombosis that are
distinct from acute myocardial necrosis. METHODS AND RESULTS: We quantified 1,032
plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic
MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time
of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up)
time points. A statistical classifier was constructed utilizing baseline (T0)
abundances of a parsimonious set of 17 qualifying metabolites. Qualifying
metabolites were those that demonstrated a significant change between the
quiescent phase and the acute phase and that were distinct from any change seen
in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated
by 10-fold cross-validation was suggestive of high sensitivity and specificity
for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at
presentation. Nineteen metabolites demonstrated an intra-subject change from time
of acute thrombotic MI presentation to the quiescent state that was distinct from
any change measured in both the non-thrombotic MI and stable CAD subjects
undergoing cardiac catheterization over the same time course (false discovery
rate <5%). CONCLUSIONS: We have identified a candidate metabolic signature that
differentiates acute thrombotic MI from quiescent state after MI, from acute non
thrombotic MI, and from stable CAD. Further validation of these metabolites is
warranted given their potential as diagnostic biomarkers and novel therapeutic
targets for the prevention or treatment of acute MI.
PMID- 28414762
TI - Transcriptional networks are associated with resistance to Mycobacterium
tuberculosis infection.
AB - RATIONALE: Understanding mechanisms of resistance to M. tuberculosis (M.tb)
infection in humans could identify novel therapeutic strategies as it has for
other infectious diseases, such as HIV. OBJECTIVES: To compare the early
transcriptional response of M.tb-infected monocytes between Ugandan household
contacts of tuberculosis patients who demonstrate clinical resistance to M.tb
infection (cases) and matched controls with latent tuberculosis infection.
METHODS: Cases (n = 10) and controls (n = 18) were selected from a long-term
household contact study in which cases did not convert their tuberculin skin test
(TST) or develop tuberculosis over two years of follow up. We obtained genome
wide transcriptional profiles of M.tb-infected peripheral blood monocytes and
used Gene Set Enrichment Analysis and interaction networks to identify cellular
processes associated with resistance to clinical M.tb infection. MEASUREMENTS AND
MAIN RESULTS: We discovered gene sets associated with histone deacetylases that
were differentially expressed when comparing resistant and susceptible subjects.
We used small molecule inhibitors to demonstrate that histone deacetylase
function is important for the pro-inflammatory response to in-vitro M.tb
infection in human monocytes. CONCLUSIONS: Monocytes from individuals who appear
to resist clinical M.tb infection differentially activate pathways controlled by
histone deacetylase in response to in-vitro M.tb infection when compared to those
who are susceptible and develop latent tuberculosis. These data identify a
potential cellular mechanism underlying the clinical phenomenon of resistance to
M.tb infection despite known exposure to an infectious contact.
PMID- 28414763
TI - Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet
is associated with epigenetic and microbiome alterations.
AB - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity
associated with obesity and a precursor to steatohepatitis. However, the
contributions of gestational and early life influences on development of NAFLD
and NASH remain poorly appreciated. METHODS: Two independent studies were
performed to examine whether maternal over-nutrition via exposure to high fat
diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and
methionine choline deficient (MCD) diets in the offspring. Offspring of both
control diet- and HFD-fed dams were weaned onto control and HFD, creating four
groups. RESULTS: When compared to their control diet-fed littermates, offspring
of HF-dams weaned onto HFD gained greater body weight; had increased relative
liver weight and showed hepatic steatosis and inflammation. Similarly, this group
revealed significantly greater immune response and pro-fibrogenic gene expression
via RNA-seq. In parallel, 7-8 week old offspring were challenged with either
control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated
due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes.
Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed
persistent epigenetic changes in key genes in tissue development and metabolism
(Fgf21, Ppargc1beta) with maternal HFD and in cell adhesion and communication
(VWF, Ephb2) in the combination of maternal HFD and offspring MCD diets. Maternal
HFD also influenced gut microbiome profiles in offspring leading to a decrease in
alpha-diversity. Linear regression analysis revealed association between serum
ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum.
CONCLUSION: Our findings indicate that maternal HFD detrimentally alters
epigenetic and gut microbiome pathways to favor development of fatty liver
disease and its progressive sequelae.
PMID- 28414764
TI - Effects of UV-B radiation on leaf hair traits of invasive plants-Combining
historical herbarium records with novel remote sensing data.
AB - Ultraviolet-B (UV-B) radiation is a key but under-researched environmental factor
that initiates diverse responses in plants, potentially affecting their
distribution. To date, only a few macroecological studies have examined
adaptations of plant species to different levels of UV-B. Here, we combined
herbarium specimens of Hieracium pilosella L. and Echium vulgare L. with a novel
UV-B dataset to examine differences in leaf hair traits between the plants'
native and alien ranges. We analysed scans of 336 herbarium specimens using
standardized measurements of leaf area, hair density (both species) and hair
length (H. pilosella only). While accounting for other bioclimatic variables
(i.e. temperature, precipitation) and effects of herbivory, we examined whether
UV-B exposure explains the variability and geographical distribution of these
traits in the native (Northern Hemisphere) vs. the alien (Southern Hemisphere)
range. UV-B explained the largest proportion of the variability and geographical
distribution of hair length in H. pilosella (relative influence 67.1%), and hair
density in E. vulgare (66.2%). Corresponding with higher UV-B, foliar hairs were
25% longer for H. pilosella and 25% denser for E. vulgare in records from the
Southern as compared to those from the Northern Hemisphere. However, focusing on
each hemisphere separately or controlling for its effect in a regression
analysis, we found no apparent influence of UV-B radiation on hair traits. Thus,
our findings did not confirm previous experimental studies which suggested that
foliar hairs may respond to higher UV-B intensities, presumably offering
protection against detrimental levels of radiation. We cannot rule out UV-B
radiation as a possible driver because UV-B radiation was the only considered
variable that differed substantially between the hemispheres, while bioclimatic
conditions (e.g. temperature, precipitation) and other considered variables
(herbivory damage, collection date) were at similar levels. However, given that
either non-significant or inconclusive relationships were detected within
hemispheres, alternative explanations of the differences in foliar hairs are more
likely, including the effects of environment, genotypes or herbivory.
PMID- 28414765
TI - Validation of full-field optical coherence tomography in distinguishing malignant
and benign tissue in resected pancreatic cancer specimens.
AB - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related
mortality in the United States. The minority of patients can undergo curative
intended surgical therapy due to progressive disease stage at time of diagnosis.
Nonetheless, tumor involvement of surgical margins is seen in up to 70% of
resections, being a strong negative prognostic factor. Real-time intraoperative
imaging modalities may aid surgeons to obtain tumor-free resection margins. Full
field optical coherence tomography (FF-OCT) is a promising diagnostic tool using
high-resolution white-light interference microscopy without tissue processing.
Therefore, we composed an atlas of FF-OCT images of malignant and benign
pancreatic tissue, and investigated the accuracy with which the pathologists
could distinguish these. MATERIALS AND METHODS: One hundred FF-OCT images were
collected from specimens of 29 patients who underwent pancreatic resection for
various indications between 2014 and 2016. One experienced gastrointestinal
pathologist and one pathologist in training scored independently the FF-OCT
images as malignant or benign blinded to the final pathology conclusion. Results
were compared to those obtained with standard hematoxylin and eosin (H&E) slides.
RESULTS: Overall, combined test characteristics of both pathologists showed a
sensitivity of 72%, specificity of 74%, positive predictive value of 69%,
negative predictive value of 79% and an overall accuracy of 73%. In the subset of
pancreatic ductal adenocarcinoma patients, 97% of the FF-OCT images (n = 35) were
interpreted as tumor by at least one pathologist. Moreover, normal pancreatic
tissue was recognised in all cases by at least one pathologist. However, atrophy
and fibrosis, serous cystadenoma and neuroendocrine tumors were more often
wrongly scored, in 63%, 100% and 25% respectively. CONCLUSION: FF-OCT could
distinguish normal pancreatic tissue from pathologic pancreatic tissue in both
processed as non-processed specimens using architectural features. The accuracy
in pancreatic ductal adenocarcinoma is promising and warrants further evaluation
using improved assessment criteria.
PMID- 28414766
TI - The metabolic basis of cognitive insight in psychosis: A positron emission
tomography study.
AB - : The purpose of this study was to investigate the relationship between cognitive
insight and cerebral metabolism in patients suffering from psychosis. The Beck
Cognitive Insight Scale (BCIS) was administered to 63 patients with psychosis
undergoing Positron Emission Tomography investigation. The sample was divided
into two groups considering the BCIS score. Data were analyzed using Statistical
Parametric Mapping. RESULTS: patients with low insight, compared to those with
high insight, showed decreased metabolism in the right fusiform gyrus, left
precuneus, superior temporal gyrus and insula bilaterally, as well as increased
metabolism in the left orbito-frontal gyrus (all p<0.005). Our results suggest
that reduced posterior (occipito-temporo-insulo-parietal) and increased anterior
(orbitofrontal) cerebral metabolism may sustain low cognitive insight in
psychosis.
PMID- 28414767
TI - The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA
interaction in vitro.
AB - The RNA-binding protein Hu antigen R (HuR) binds to AU-rich elements (ARE) in the
3'-untranslated region (UTR) of target mRNAs. The HuR-ARE interactions stabilize
many oncogenic mRNAs that play important roles in tumorigenesis. Thus, small
molecules that interfere with the HuR-ARE interaction could potentially inhibit
cancer cell growth and progression. Using a fluorescence polarization (FP)
competition assay, we identified the compound azaphilone-9 (AZA-9) derived from
the fungal natural product asperbenzaldehyde, binds to HuR and inhibits HuR-ARE
interaction (IC50 ~1.2 MUM). Results from surface plasmon resonance (SPR)
verified the direct binding of AZA-9 to HuR. NMR methods mapped the RNA-binding
interface of HuR and identified the involvement of critical RNA-binding residues
in binding of AZA-9. Computational docking was then used to propose a likely
binding site for AZA-9 in the RNA-binding cleft of HuR. Our results show that AZA
9 blocks key RNA-binding residues of HuR and disrupts HuR-RNA interactions in
vitro. This knowledge is needed in developing more potent AZA-9 derivatives that
could lead to new cancer therapy.
PMID- 28414768
TI - GPATCH3 negatively regulates RLR-mediated innate antiviral responses by
disrupting the assembly of VISA signalosome.
AB - Upon viral infection, retinoic acid-inducible gene I-like receptors (RLRs)
recognize viral RNA and trigger a series of signaling events, leading to the
induction of type I interferons (IFNs). These processes are delicately regulated
to prevent excessive and harmful immune responses. In this study, we identified G
patch domain-containing protein 3 (GPATCH3) as a negative regulator of RLR
mediated antiviral signaling pathways. Overexpression of GPATCH3 impaired RNA
virus- triggered induction of downstream antiviral genes, whereas its knockdown
had opposite effects and attenuated viral replication. In addition, GPATCH3
deficient cells had higher IFNB1 mRNA level compared with control cells after RNA
virus infection. Mechanistically, GPATCH3 was recruited to VISA in a viral
infection dependent manner and the assembly of VISA/TRAF6/TBK1 signalosome was
impaired in GPATCH3-overexpressing cells. In contrast, upon viral infection, the
recruitment of TRAF6 and TBK1 to VISA was enhanced in GPATCH3 deficient cells.
Taking together, our findings demonstrate that GPATCH3 interacts with VISA and
disrupts the assembly of virus-induced VISA signalosome therefore acts as a
negative regulator of RLR-mediated innate antiviral immune responses.
PMID- 28414769
TI - Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after
spinal cord contusion in rats for eventual intralesional implantation of
restorative materials.
AB - Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the
site of injury and adjacent segments. It is considered harmful because of its
potential to aggravate secondary injury, and to interfere with axonal
regeneration; it might also lead to an unfavorable environment for intralesional
implants. Removal of hemorrhagic necrosis has been attempted before with variable
results. The invasive nature of these procedures carries the risk of exacerbating
damage to the injured cord. The overall objective for this study was to test
several strategies for non-damaging removal of hemorrhagic necrosis and
characterize the resulting cavity looking for a space for future intralesional
therapeutic implants in rats with acute cord injury. Rats were subjected to
graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three
grades of myelotomy (extensive, medium sized, and small) were tested. Using the
small surgical approach to debridement, early and late effects of the
intervention were determined by histology and by analytical and behavioral
analysis. Appearance and capacity of the resulting cavity were characterized.
Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical
approaches to debridement. However, bleeding in spared cord tissue was excessive
after medium sized and extensive myelotomies but similar to control injured rats
after small cord surgery. Small surgical approach to debridement produced no
swelling nor acute inflammation changes, nor did it affect long-term spontaneous
locomotor recovery, but resulted in modest improvement of myelination in rats
subjected to both moderate and severe injuries. Cavity created after intervention
was filled with 10 to 15 MUL of hydrogel. In conclusion, by small surgical
approach to debridement, removal of hemorrhagic necrosis was achieved after acute
cord contusion thereby creating intramedullary spaces without further damaging
the injured spinal cord. Resulting cavities appear suitable for future
intralesional placement of pro-reparative cells or other regenerative
biomaterials in a clinically relevant model of spinal cord injury.
PMID- 28414770
TI - Correction: Efficient and robust differentiation of endothelial cells from human
induced pluripotent stem cells via lineage control with VEGF and cyclic AMP.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173271.].
PMID- 28414771
TI - Stability of gabapentin in extemporaneously compounded oral suspensions.
AB - This study reports the stability of extemporaneously prepared gabapentin oral
suspensions prepared at 100 mg/mL from bulk drug and capsules in either Oral Mix
or Oral Mix SF suspending vehicles. Suspensions were packaged in amber plastic
bottles and amber plastic syringes at 25 degrees C / 60%RH for up to 90 days.
Throughout the study period, the following tests were performed to evaluate the
stability of the preparations: organoleptic inspection to detect homogeneity,
color or odor changes; pH measurements; and gabapentin assay using a stability
indicating HPLC-UV method. As crystallization was observed at 5 degrees C,
storage at this temperature condition is not recommended. All preparations stored
at 25 degrees C / 60%RH remained stable for the whole study duration of 90 days.
PMID- 28414772
TI - The nanoparticle protein corona formed in human blood or human blood fractions.
AB - The protein corona formed around nanoparticles in protein-rich fluids plays an
important role for nanoparticle biocompatibility, as found in several studies
during the last decade. Biological fluids have complex compositions and the
molecular components interact and function together in intricate networks.
Therefore, the process to isolate blood or the preparation of blood derivatives
may lead to differences in the composition of the identified protein corona
around nanoparticles. Here, we show distinct differences in the protein corona
formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the
ratio between particle surface area to protein concentration influences the
detected corona. We also show that the nanoparticle size per se influences the
formed protein corona due to curvature effects. These results emphasize the need
of investigating the formation and biological importance of the protein corona in
the same environment as the nanoparticles are intended for or released into.
PMID- 28414773
TI - The importance of calcium in improving resistance of Daphnia to Microcystis.
AB - Changing environmental calcium (Ca) and rising cyanobacterial blooms in lake
habitats could strongly reduce Daphnia growth and survival. Here, we assessed the
effects of maternal Ca in Daphnia on transfer of resistance to their offspring
against Microcystis aeruginosa PCC7806 (M. aeruginosa). Laboratory microcosm
experiments were performed to examine effects in Daphnia carinata (D. carinata)
and Daphnia pulex (D. pulex), and that how Ca induce responses in their
offspring. The results showed that growth and survival were increased in
offspring from exposed Daphnia as compared to unexposed, when raised in high Ca
and increasing M. aeruginosa concentration. Among exposed Daphnia, offspring from
high Ca mothers, produced more neonates with large size and higher survival as
compared to offspring from low maternal Ca. Exposed D. carinata and D. pulex
offspring, when reared in Ca deficient medium and increasing M. aeruginosa
concentration, time to first brood increased, size become large and total
offspring decreased subsequently in three alternative broods in offspring from
low maternal Ca. In contrast, growth and reproduction in offspring from high Ca
exposed mothers were consistent in three alternative broods. Despite species
specific responses in growth, survival and variant life history traits in two
Daphnia species, our results not only show maternal induction in Daphnia but also
highlight that offspring response to M. aeruginosa varies with maternal Ca. This
study demonstrates that Ca have role in Daphnia maternal induction against
Microcystis, and recent Ca decline and increasing Microcystis concentration in
lakes may decrease Daphnia growth and survival. Our data provide insights into
the interactive effect of maternal Ca and Microcystis exposure on Daphnia and
their outcome on offspring life history traits and survival.
PMID- 28414776
TI - Correction: Malignant infarction of the middle cerebral artery in a porcine
model. A pilot study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172637.].
PMID- 28414774
TI - Mycobacterium marinum antagonistically induces an autophagic response while
repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.
AB - Autophagy is a eukaryotic catabolic process also participating in cell-autonomous
defence. Infected host cells generate double-membrane autophagosomes that mature
in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However,
several bacteria subvert autophagy and benefit from its machinery and functions.
Monitoring infection stages by genetics, pharmacology and microscopy, we
demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close
relative to M. tuberculosis, upregulates the transcription of autophagy genes,
and stimulates autophagosome formation and recruitment to the mycobacteria
containing vacuole (MCV) in the host model organism Dictyostelium.
Antagonistically, ESX-1 is also essential to block the autophagic flux and
deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize
to the MCV in an ESX-1-dependent manner, suggesting an important role in the
manipulation of autophagy by mycobacteria. Our findings suggest that the
infection by M. marinum activates an autophagic response that is simultaneously
repressed and exploited by the bacterium to support its survival inside the MCV.
PMID- 28414775
TI - Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of
syndromic X-linked intellectual disability.
AB - By searching a clinical database of over 60,000 individuals referred for array
based CNV analyses and online resources, we identified four males from three
families with intellectual disability, developmental delay, hypotonia, joint
hypermobility and relative macrocephaly who carried small, overlapping deletions
of Xp11.22. The maximum region of overlap between their deletions spanned ~430 kb
and included two pseudogenes, CENPVL1 and CENPVL2, whose functions are not known,
and two protein coding genes-the G1 to S phase transition 2 gene (GSPT2) and the
MAGE family member D1 gene (MAGED1). Deletions of this ~430 kb region have not
been previously implicated in human disease. Duplications of GSPT2 have been
documented in individuals with intellectual disability, but the phenotypic
consequences of a loss of GSPT2 function have not been elucidated in humans or
mouse models. Changes in MAGED1 have not been associated with intellectual
disability in humans, but loss of MAGED1 function is associated with
neurocognitive and neurobehavioral phenotypes in mice. In all cases, the Xp11.22
deletion was inherited from an unaffected mother. Studies performed on DNA from
one of these mothers did not show evidence of skewed X-inactivation. These
results suggest that deletions of an ~430 kb region on chromosome Xp11.22 that
encompass CENPVL1, CENPVL2, GSPT2 and MAGED1 cause a distinct X-linked syndrome
characterized by intellectual disability, developmental delay, hypotonia, joint
hypermobility and relative macrocephaly. Loss of GSPT2 and/or MAGED1 function may
contribute to the intellectual disability and developmental delay seen in males
with these deletions.
PMID- 28414777
TI - A unified approach for determining the ultimate strength of RC members subjected
to combined axial force, bending, shear and torsion.
AB - This paper uses experimental investigation and theoretical derivation to study
the unified failure mechanism and ultimate capacity model of reinforced concrete
(RC) members under combined axial, bending, shear and torsion loading. Fifteen RC
members are tested under different combinations of compressive axial force,
bending, shear and torsion using experimental equipment designed by the authors.
The failure mechanism and ultimate strength data for the four groups of tested RC
members under different combined loading conditions are investigated and
discussed in detail. The experimental research seeks to determine how the
ultimate strength of RC members changes with changing combined loads. According
to the experimental research, a unified theoretical model is established by
determining the shape of the warped failure surface, assuming an appropriate
stress distribution on the failure surface, and considering the equilibrium
conditions. This unified failure model can be reasonably and systematically
changed into well-known failure theories of concrete members under single or
combined loading. The unified calculation model could be easily used in design
applications with some assumptions and simplifications. Finally, the accuracy of
this theoretical unified model is verified by comparisons with experimental
results.
PMID- 28414778
TI - Correction: A novel hemagglutinin protein produced in bacteria protects chickens
against H5N1 highly pathogenic avian influenza viruses by inducing H5 subtype
specific neutralizing antibodies.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172008.].
PMID- 28414779
TI - Seed germination in relation to the invasiveness in spiny amaranth and edible
amaranth in Xishuangbanna, SW China.
AB - Both spiny and edible amaranths (Amaranthus spinosus and A. tricolor) are exotic
annuals in China that produce numerous small seeds every year. Spiny amaranth has
become a successful invader and a troublesome weed in Xishuangbanna, but edible
amaranth has not, although it is widely grown as a vegetable there. As seed
germination is one of the most important life-stages contributing to the ability
of a plant to become invasive, we conducted experiments to compare the effects of
high temperature and water stress on seed germination in two varieties each of
spiny amaranth and edible amaranth. Overall, the seeds of both amaranth species
exhibited adaptation to high temperature and water stress, including tolerance to
ground temperatures of 70 degrees C for air-dried seeds, which is consistent with
their behavior in their native ranges in the tropics. As expected, the invasive
spiny amaranth seeds exhibited higher tolerance to both continuous and daily
periodic high-temperature treatment at 45 degrees C, and to imbibition
desiccation treatment, compared to edible amaranth seeds. Unexpectedly, edible
amaranth seeds exhibited higher germination at extreme temperatures (10 degrees
C, 15 degrees C, and 40 degrees C), and at lower water potential (below -0.6
MPa). It is likely that cultivation of edible amaranth has selected seed traits
that include rapid germination and germination under stressful conditions, either
of which, under natural conditions, may result in the death of most germinating
edible amaranth seeds and prevent them from becoming invasive weeds in
Xishuangbanna. This study suggests that rapid germination and high germination
under stress conditions-excellent seed traits for crops and for many invasive
species-might be a disadvantage under natural conditions if these traits are
asynchronous with natural local conditions that support successful germination.
PMID- 28414781
TI - Voice disorder in systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) is a chronic disease characterized by
progressive tissue damage. In recent decades, novel treatments have greatly
extended the life span of SLE patients. This creates a high demand for
identifying the overarching symptoms associated with SLE and developing therapies
that improve their life quality under chronic care. We hypothesized that SLE
patients would present dysphonic symptoms. Given that voice disorders can reduce
life quality, identifying a potential SLE-related dysphonia could be relevant for
the appraisal and management of this disease. We measured objective vocal
parameters and perceived vocal quality with the GRBAS (Grade, Roughness,
Breathiness, Asthenia, Strain) scale in SLE patients and compared them to matched
healthy controls. SLE patients also filled a questionnaire reporting perceived
vocal deficits. SLE patients had significantly lower vocal intensity and
harmonics to noise ratio, as well as increased jitter and shimmer. All subjective
parameters of the GRBAS scale were significantly abnormal in SLE patients.
Additionally, the vast majority of SLE patients (29/36) reported at least one
perceived vocal deficit, with the most prevalent deficits being vocal fatigue
(19/36) and hoarseness (17/36). Self-reported voice deficits were highly
correlated with altered GRBAS scores. Additionally, tissue damage scores in
different organ systems correlated with dysphonic symptoms, suggesting that some
features of SLE-related dysphonia are due to tissue damage. Our results show that
a large fraction of SLE patients suffers from perceivable dysphonia and may
benefit from voice therapy in order to improve quality of life.
PMID- 28414780
TI - Sensitive quantification of the HIV-1 reservoir in gut-associated lymphoid
tissue.
AB - BACKGROUND: The implementation of successful strategies to achieve an HIV cure
has become a priority in HIV research. However, the current location and size of
HIV reservoirs is still unknown since there are limited tools to evaluate HIV
latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As
reported in the so called "Boston Patients", despite undetectable levels of
proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months
after ART interruption. This fact might imply that current methods are not
sensitive enough to detect residual reservoirs. Showing that, it is imperative to
improve the detection and quantification of HIV-1 reservoir in tissue samples.
Herein, we propose a novel non-enzymatic protocol for purification of Lamina
Propria Leukocytes (LPL) from gut biopsies combined to viral HIV DNA (vDNA)
quantification by droplet digital PCR (ddPCR) to improve the sensitivity and
accuracy of viral reservoir measurements (LPL-vDNA assay). METHODS: Endoscopic
ileum biopsies were sampled from 12 HIV-1-infected cART-suppressed subjects. We
performed a DTT/EDTA-based treatment for epithelial layer removal followed by non
enzymatic disruption of the tissue to obtain lamina propria cell suspension (LP).
CD45+ cells were subsequently purified by flow sorting and vDNA was determined by
ddPCR. RESULTS: vDNA quantification levels were significantly higher in purified
LPLs (CD45+) than in bulk LPs (p<0.01). The levels of vDNA were higher in ileum
samples than in concurrent PBMC from the same individuals (p = 0.002). As a
result of the increased sensitivity of this purification method, the Poisson 95%
confidence intervals of the vDNA quantification data from LPLs were narrower than
that from bulk LPs. Of note, vDNA was unambiguously quantified above the
detection limit in 100% of LPL samples, while only in 58% of bulk LPs.
CONCLUSION: We propose an innovative combined protocol for a more sensitive
detection of the HIV reservoir in gut-associated viral sanctuaries, which might
be used to evaluate any proposed eradication strategy.
PMID- 28414782
TI - Identification of the chain-dispersing peptidoglycan hydrolase LytB of
Streptococcus gordonii.
AB - Bacterial cell division ends with the separation of the daughter cells, a process
that requires peptidoglycan hydrolases (PGHs). Bacteria lacking cell separating
PGHs are impaired in cell separation with the formation of long chains or
clusters. We identified a gene in Streptococcus gordonii encoding for a putative
glucosaminidase (lytB). The lytB isogenic mutant grew in long bacterial chains
and resulted in impaired biofilm formation. Purified recombinant LytB showed a
murolytic activity on Micrococcus lysodeikticus cell suspension and was able to
disperse the long chains of the mutant, restoring the wild type diplococci/short
chain phenotype. LytB protein was localized only in culture supernatant cell
fraction of S. gordonii, and co-cultures of wild type and lytB mutant showed a
significant reduction of bacterial chain length, indicating that LytB is a
secreted enzyme. Our results demonstrate that LytB is a secreted peptidoglycan
hydrolase required for S. gordonii cell separation.
PMID- 28414784
TI - Savanna elephant numbers are only a quarter of their expected values.
AB - Savannas once constituted the range of many species that human encroachment has
now reduced to a fraction of their former distribution. Many survive only in
protected areas. Poaching reduces the savanna elephant, even where protected,
likely to the detriment of savanna ecosystems. While resources go into estimating
elephant populations, an ecological benchmark by which to assess counts is
lacking. Knowing how many elephants there are and how many poachers kill is
important, but on their own, such data lack context. We collated savanna elephant
count data from 73 protected areas across the continent estimated to hold ~50% of
Africa's elephants and extracted densities from 18 broadly stable population time
series. We modeled these densities using primary productivity, water
availability, and an index of poaching as predictors. We then used the model to
predict stable densities given current conditions and poaching for all 73
populations. Next, to generate ecological benchmarks, we predicted such densities
for a scenario of zero poaching. Where historical data are available, they
corroborate or exceed benchmarks. According to recent counts, collectively, the
73 savanna elephant populations are at 75% of the size predicted based on current
conditions and poaching levels. However, populations are at <25% of ecological
benchmarks given a scenario of zero poaching (~967,000)-a total deficit of
~730,000 elephants. Populations in 30% of the 73 protected areas were <5% of
their benchmarks, and the median current density as a percentage of ecological
benchmark across protected areas was just 13%. The ecological context provided by
these benchmark values, in conjunction with ongoing census projects, allow
efficient targeting of conservation efforts.
PMID- 28414783
TI - Acceptability and feasibility of early infant male circumcision for HIV
prevention in Malawi.
AB - BACKGROUND: Voluntary medical male circumcision (VMMC) has been successfully
implemented in 14 countries as an additional HIV prevention intervention. As VMMC
programs mature in most countries, the focus is now on how to sustain the HIV
prevention gains realised from VMMC. As part of preparations for the
sustainability phase, countries are either piloting or preparing to pilot early
infant male circumcision (EIMC). This qualitative study explored the
acceptability and feasibility of EIMC in Malawi in order to inform pilot
implementation. METHODS: In 2016, 23 focus group discussions were held across
Malawi with participants from several ethnicities and religions/faiths.
Additionally, 21 key informant interviews were held with traditional and
religious leaders, traditional circumcisers (ngalibas), policy-makers, programme
managers and health-care workers. Audio recordings were transcribed, translated
into English (where necessary), and thematically coded using NVivo 10. RESULTS:
Discussions highlighted the socio-cultural significance of MC in Malawi.
Knowledge or experience of EIMC was poor although acceptability was high among
most ethnic/religious groups and key informants. Participants identified EIMC's
comparative HIV benefits although a few health-care workers expressed scepticism.
All participants said EIMC should be offered within a clinical setting. In
addition to fathers, maternal uncles and traditional leaders were deemed key
decision-makers. Potential barriers to EIMC included concerns about procedure
safety as well as cultural considerations. Key informants felt it was feasible to
offer EIMC in Malawi. Participants' recommendations, including phased
implementation, engagement of traditional leaders, use of external mobilisers and
initially reaching out to influential parents, will be taken into account when
designing a pilot EIMC program. CONCLUSIONS: EIMC is potentially an acceptable
and feasible HIV prevention intervention for most ethnic/religious groups in
Malawi if wide-ranging, culturally appropriate demand-creation activities are
developed, piloted, evaluated and appropriately implemented.
PMID- 28414785
TI - The Epstein-Barr virus miR-BHRF1-1 targets RNF4 during productive infection to
promote the accumulation of SUMO conjugates and the release of infectious virus.
AB - Post-translational modification by the Small Ubiquitin-like Modifier (SUMO)
regulates a variety of cellular functions, and is hijacked by viruses to remodel
the host cell during latent and productive infection. Here we have monitored the
activity of the SUMO conjugation machinery in cells productively infected with
Epstein-Barr virus (EBV). We found that SUMO2/3 conjugates accumulate during the
late phase of the productive virus cycle, and identified several viral proteins
as bone fide SUMOylation substrates. Analysis of the mechanism involved in the
accumulation of SUMOylated proteins revealed upregulation of several components
of the SUMO-conjugation machinery and post-transcriptional downregulation of the
SUMO-targeted ubiquitin ligase RNF4. The latter effect was mediated by selective
inhibition of RNF4 protein expression by the viral miR-BHRF1-1. Reconstitution of
RNF4 in cells expressing an inducible miR-BHRF1-1 sponge or a miR-BHRF1-1
resistant RNF4 was associated with reduced levels of early and late viral
proteins and impaired virus release. These findings illustrate a novel strategy
for viral interference with the SUMO pathway, and identify the EBV miR-BHRF1-1
and the cellular RNF4 as regulators of the productive virus cycle.
PMID- 28414786
TI - The Model for End-stage Liver Disease (MELD) as a predictor of short-term
mortality in Staphylococcus aureus bloodstream infection: A single-centre
observational study.
AB - BACKGROUND: Automated laboratory-based prediction models may support clinical
decisions in Staphylococcus aureus bloodstream infections (BSIs), which carry a
particularly high mortality. Small studies indicated that the laboratory-based
Model for End-stage Liver Disease (MELD) score is a risk factor for mortality in
critically ill patients with infections. For S. aureus BSIs, we therefore aimed
to assess a potential association of the MELD score with mortality. METHODS: In
this single-centre observational study, all consecutive patients with a first
episode of methicillin-susceptible S. aureus BSI occurring between 2001 and 2013
were eligible. Relevant patient data were retrieved from our prospective in-house
BSI database. We assessed the association of the MELD score at day of BSI onset
(range +/- two days) with 30-day all-cause mortality using uni- and multivariable
logistic regression analysis. RESULTS: 561 patients were included in the final
analysis. The MELD score at BSI onset was associated with 30-day mortality in S.
aureus BSIs (odds ratio per 1-point increase, 1.06; 95% confidence interval, 1.03
1.09; P < 0.001). After adjustment for relevant patient and infection
characteristics, an increased MELD score remained a predictor of 30-day mortality
(adjusted odds ratio per 1-point increase, 1.05; 95% confidence interval, 1.01
1.08; P = 0.005). CONCLUSIONS: In our study population, the MELD score at BSI
onset was an independent predictor of mortality in S. aureus BSIs. We therefore
suggest to prospectively validate the MELD score as part of clinical decision
support systems in inpatients with suspected or confirmed BSI.
PMID- 28414787
TI - Water abstraction affects abundance, size-structure and growth of two threatened
cyprinid fishes.
AB - Hydrologic alteration is a major threat to freshwater biota, and particularly
fish, in many river courses around the world. We analyzed and compared the
effects of water abstraction on two threatened cyprinid fishes of contrasting
ecology (the Mediterranean barbel Barbus meridionalis and the Catalan chub
Squalius laietanus) in a Mediterranean stream. We compared abundance, size
structure, growth, and condition of both species across perennial and
artificially intermittent reaches affected by water abstraction. Both species
were less abundant, had scarce large individuals, and displayed slower growth
rates (length-at-age) in intermittent reaches, showing clear detrimental effects
of water diversion. Mixed-effect models of scale increments showed variation
among individuals and among sites, years and age classes for both species. The
larger-sized, water-column species (chub) disappeared or was rare in many
intermittent reaches. The barbel present in intermittent reaches showed better
somatic condition than in sites with permanent flow, perhaps due to reduced
competition after rewetting or colonization by better fitted individuals. This
benthic, rheophilic species seems more resilient to moderate water abstraction
than chub. Many effects of water flow intermittency were only detected on fish
life-history traits when accounting for natural, often non-linear, variation,
along upstream-downstream gradients. Our results suggest that abundance was the
strongest indicator of effects of water abstraction on fish populations, whereas
condition was a more labile trait, rapidly recovering from anthropogenic
disturbance.
PMID- 28414788
TI - Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a
higher risk of miscarriage: A systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the relationship between subclinical hypothyroidism (SCH)
and the risk of miscarriage before 20 weeks of pregnancy. METHODS: Literature
databases were searched, including the PubMed, Web of Science, Embase and
Cochrane databases, from January 1, 1980, to December 31, 2015. The following
search terms were used: subclinical hypothyroidism, hypothyroidism, thyroid
dysfunction, thyroid hypofunction, subclinical thyroid disease, thyroid
dysfunction, pregnancy loss, abortion and miscarriage. Studies comparing the
prevalence of miscarriage in pregnant women with SCH with those who were
euthyroid were selected. From the studies matched, the relative risk (RR) and
corresponding 95% confidence interval (95% CI) were calculated to yield outcomes.
All the statistical analyses were performed using Review Manager (Revman) Version
5.3 and Stata Version 12.0 software. The publication bias of the studies was
assessed by forest plot and Begg's test, while the stability of the results was
evaluated by sensitivity analysis. RESULTS: Nine articles satisfying the
inclusion criteria were analysed. Compared to euthyroid pregnant women, patients
with non-treated SCH had a higher prevalence of miscarriage (RR = 1.90, 95%
CI1.59-2.27, P<0.01). Additionally, SCH patients in the international diagnostic
criteria group were more likely to suffer miscarriages than those in the ATA
diagnostic criteria group (chi2 = 11.493, P<0.01). Moreover, there was no
difference between patients with treated SCH and euthyroid women (RR = 1.14, 95%
CI0.82-1.58, P = 0.43). Compared to isolated SCH women, the miscarriage risk of
SCH patients with thyroid autoimmunity (TAI) was obviously higher (RR = 2.47, 95%
CI1.77-3.45, P<0.01), and isolated SCH patients also had a higher prevalence of
miscarriages than euthyroid women (RR = 1.45, 95% CI1.07-1.96, P = 0.02).A
heterogeneity test, forest plot and Begg's test suggested that there was no
significant heterogeneity or publication bias among the included articles, while
the result of sensitivity analysis showed that our study exhibited high
stability. CONCLUSION: SCH is a risk factor for miscarriage in women before 20
weeks of pregnancy, and early treatments can reduce the miscarriage rate.
Regardless of the diagnostic criteria used, the miscarriage rate increased as
long as a pregnant woman was confirmed to have SCH. The results show that the
omission diagnostic rate may increase when the ATA diagnostic criteria are used.
In addition, SCH patients with TAI have a higher prevalence of miscarriage, while
isolated SCH patients also have a higher miscarriage rate than euthyroid women.
Thus, we recommend early treatments to avoid adverse pregnancy outcomes and
complications.
PMID- 28414789
TI - Effect of pH on temperature controlled degradation of reactive oxygen species,
heat shock protein expression, and mucosal immunity in the sea cucumber
Isostichopus badionotus.
AB - This study evaluated the effect of pH on the activity of antioxidant and immune
enzymes in the sea cucumber Isostichopus badionotus exposed to different
temperatures. The organisms (530 +/-110 g) were exposed to 16, 20, 24, 28, 30, 34
and 36 degrees C for 6 h to evaluate thermal limits at two water pH values
(treatment = 7.70; control = 8.17). For the thermal tolerance experiment, the
organisms were exposed to sublethal temperature of 34 degrees C for 3, 6, 12, 24,
and 48 h. I. badionotus showed signs of thermal stress by synthesizing heat shock
protein 70 (hsp70) at the cold (16 degrees C) and warm thermal limits (34 degrees
C). The glutathione peroxidase (GPx) showed a negative correlation with
superoxide dismutase (SOD) activity in modulating the effect of oxidative stress
at different temperature levels. Specifically, GPx activity was maximal at the
extremes of the cold and warm temperatures (16, 20, and 36 degrees C) tested,
while contrarily, the SOD activity increased significantly in the narrow range of
temperature between 28 and 30 degrees C, as a part of a reaction to offset
oxidative damage. The effect of pH on the expression of hsp70 was not
significant, whereas the antioxidant enzymes activity was stimulated at pH 7.70.
Mucosal immunity, evidenced by the activation of the phenoloxidase (PO) system,
increased above the basal level at pH 7.70 and at 28, 30, and 34 degrees C.
Independent of pH, the temperature of 34 degrees C was identified as the 12 h
sublethal upper limit for I. badionotus.
PMID- 28414790
TI - Correction: Influence of intraocular lens subsurface nanoglistenings on
functional visual acuity.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173574.].
PMID- 28414791
TI - Speciation in progress? A phylogeographic study among populations of Hemitrichia
serpula (Myxomycetes).
AB - Myxomycetes (plasmodial slime molds, Amoebozoa) are often perceived as widely
distributed, confounding to the "everything is everywhere" hypothesis. To test if
gene flow within these spore-dispersed protists is restricted by geographical
barriers, we chose the widespread but morphologically unmistakable species
Hemitrichia serpula for a phylogeographic study. Partial sequences from nuclear
ribosomal RNA genes (SSU) revealed 40 ribotypes among 135 specimens, belonging to
three major clades. Each clade is dominated by specimens from a certain region
and by one of two morphological varieties which can be differentiated by SEM
micrographs. Partial sequences of the protein elongation factor 1 alpha (EF1A)
showed each clade to possess a unique combination of SSU and EF1A genotypes. This
pattern is best explained assuming the existence of several putative biospecies
dominating in a particular geographical region. However, occasional mismatches
between molecular data and morphological characters, but as well heterogeneous
SSU and heterozygous EF1A sequences, point to ongoing speciation. Environmental
niche models suggest that the putative biospecies are rather restricted by
geographical barriers than by macroecological conditions. Like other protists,
myxomycetes seem to follow the moderate endemicity hypothesis and are in active
speciation, which is most likely shaped by limited gene flow and reproductive
isolation.
PMID- 28414792
TI - Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of
Niemann-Pick Disease type C1.
AB - 2-Hydroxypropyl-beta-cyclodextrin (HPbetaCD) has gained recent attention as a
potential therapeutic intervention in the treatment of the rare autosomal
recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type
C1 (NPC1). Notably, HPbetaCD formulations are not comprised of a single molecular
species, but instead are complex mixtures of species with differing degrees of
hydroxypropylation of the cyclodextrin ring. The degree of substitution is a
critical aspect of the complex mixture as it influences binding to other
molecules and thus could potentially modulate biological effects. VTS-270
(Kleptose HPB) and Trappsol(r) CycloTM are HPbetaCD products under investigation
as novel treatments for NPC1. The purpose of the present work is to compare these
two different products; analyses were based on ion distribution and abundance
profiles using mass spectrometry methodology as a means for assessing key
molecular distinctions between products. The method incorporated electrospray
ionization and analysis with a linear low-field ion mobility quadrupole time-of
flight instrument. We observed that the number of hydroxypropyl groups (the
degrees of substitution) are substantially different between the two products and
greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are
ammonium adducts. Isotope clusters for each of the major ions show doubly charged
homodimers of the ammonium adducts. In addition, both products show doubly
charged homodimers from adduction of both a proton and ammonium. Doubly charged
heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS
270. Based on the analytical differences observed between VTS-270 and Trappsol
Cyclo with respect to the degree of substitution, the composition and fingerprint
of the complex mixture, and the impurity profiles, these products cannot be
considered to be the same; the potential biological and clinical implications of
these differences are not presently known.
PMID- 28414793
TI - Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt
signaling pathway.
AB - Radiotherapy is a powerful tool in the treatment of cancer that has the advantage
of preserving normal tissues. However, tumor radioresistance currently remains a
major impediment to effective RT. Thus, exploring effective radiation sensitizers
is urgently needed. In this study, we have shown that diosmetin, the aglycone of
the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs,
has a promising effect on radiotherapy sensitization. In our results, DIO could
induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant
A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA
damage repair by inhibiting the activated Akt signaling pathway. The combination
of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked
A549/IR cancer cell proliferation. In summary, these observations suggest that
the natural compound DIO could act as a potential drug for the treatment of
radioresistant lung cancer cells.
PMID- 28414794
TI - Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced
acute ileitis in mice harboring a human gut microbiota.
AB - BACKGROUND: Within seven days following peroral high dose infection with
Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis
due to an underlying T helper cell (Th) -1 type immunopathology. We here
addressed whether mice harboring a human intestinal microbiota developed
intestinal, extra-intestinal and systemic sequelae upon ileitis induction.
METHODOLOGY/PRINCIPAL FINDINGS: Secondary abiotic mice were generated by broad
spectrum antibiotic treatment and associated with a complex human intestinal
microbiota following peroral fecal microbiota transplantation. Within three weeks
the human microbiota had stably established in the murine intestinal tract as
assessed by quantitative cultural and culture-independent (i.e. molecular 16S
rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii
strain ME49 by gavage human microbiota associated (hma) mice displayed severe
clinical, macroscopic and microscopic sequelae indicating acute ileitis. In
diseased hma mice increased numbers of innate and adaptive immune cells within
the ileal mucosa and lamina propria and elevated intestinal secretion of pro
inflammatory mediators including IFN-gamma, IL-12 and nitric oxide could be
observed at day 7 p.i. Ileitis development was accompanied by substantial shifts
in intestinal microbiota composition of hma mice characterized by elevated total
bacterial loads and increased numbers of intestinal Gram-negative commensals such
as enterobacteria and Bacteroides / Prevotella species overgrowing the small and
large intestinal lumen. Furthermore, viable bacteria translocated from the
inflamed ileum to extra-intestinal including systemic compartments. Notably, pro
inflammatory immune responses were not restricted to the intestinal tract as
indicated by increased pro-inflammatory cytokine secretion in extra-intestinal
(i.e. liver and kidney) and systemic compartments including spleen and serum.
CONCLUSION/SIGNIFICANCE: With respect to the intestinal microbiota composition
"humanized" mice display acute ileitis following peroral high dose T. gondii
infection. Thus, hma mice constitute a suitable model to further dissect the
interactions between pathogens, human microbiota and vertebrate host immunity
during acute intestinal inflammation.
PMID- 28414795
TI - Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1.
AB - Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at
gene promoter regions critically regulates gene expression. Key developmental
genes tend to exhibit changes in histone modification patterns from the
H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using
comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow
derived macrophages (BMMs) and mature osteoclasts, we found that cell surface
adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T
cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent
pattern in osteoclasts. Cadm1 expression was upregulated in BMMs by receptor
activator of nuclear factor kappa B ligand (RANKL), and blocked by a
calcineurin/NFATc1 inhibitor, FK506. Cadm1-deficient mice exhibited significantly
reduced bone mass compared with wild-type mice, which was due to the increased
osteoclast differentiation, survival and bone-resorbing activity in Cadm1
deficient osteoclasts. These results suggest that Cadm1 is a direct target of
NFATc1, which is induced by RANKL through epigenetic modification, and regulates
osteoclastic bone resorption in a negative feedback manner.
PMID- 28414796
TI - Post-ischemic stroke rehabilitation is associated with a higher risk of fractures
in older women: A population-based cohort study.
AB - BACKGROUND: Rehabilitation can improve physical activity after stroke. However,
patients may be more prone to falls and fractures because of balance and gait
deficits. Few reports have studied the relationship between rehabilitation and
subsequent fractures after ischemic stroke. OBJECTIVE: To investigate whether
post-stroke rehabilitation affects fracture risk. METHODS: We conducted a
population-based retrospective cohort study based on the Taiwan National Health
Insurance Research Database. Patients with a newly diagnosed ischemic stroke
between 2000 and 2012 were included. After propensity score matching, a total of
8,384 patients were enrolled. Half of the patients (4,192) received post-stroke
rehabilitation within 1 month; the other half did not receive any post-stroke
rehabilitation. Cox proportional hazards regression model was used to calculate
hazard ratios (HRs) for fractures among patients with and without rehabilitation
within 1 year after ischemic stroke. Patients were further stratified by sex and
age (20-64 and >=65 years). RESULTS: Patients receiving post-stroke
rehabilitation had a higher incidence of fracture (6.2 per 100 person-years) than
those who did not (4.1 per 100 person-years) after adjustment for
sociodemographic and coexisting medical conditions [HR = 1.53, 95% confidence
interval (CI) = 1.25-1.87, p < 0.001]. The analyses performed after stratifying
for sex and age showed that only older women undergoing rehabilitation had a
significantly higher risk of fracture (HR = 1.62, 95% CI = 1.21-2.17, p = 0.001).
CONCLUSION: Rehabilitation after ischemic stroke is associated with an increased
fracture risk in older women.
PMID- 28414798
TI - Correction: Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle
Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term
Murine Model of Tripanosoma cruzi Infection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0153038.].
PMID- 28414797
TI - BIG1 is required for the survival of deep layer neurons, neuronal polarity, and
the formation of axonal tracts between the thalamus and neocortex in developing
brain.
AB - BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1
gene, is one of candidate genes for epileptic encephalopathy. To know the
involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice
and found that BIG1 regulates neurite outgrowth and brain development in vitro
and in vivo. The loss of BIG1 decreased the size of the neocortex and
hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the
interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons
showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed
from the piriform cortex (PIR), peaked in the neocortex, and then progressed into
the hippocampus from embryonic day 13.5 (E13.5) to E17.5. The upper layer (UL)
and DL order in the neocortex was maintained in BIG1-deficient mice, but the
excitatory neurons tended to accumulate before their destination layers. Further
pulse-chase migration assay showed that the migration defect was non-cell
autonomous and secondary to the progression of apoptosis into the BIG1-deficient
neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection
of corticothalamic axons from the primary somatosensory cortex (S1) into the
dorsal lateral geniculate nucleus (dLGN). The thalamocortical axons were unable
to cross the diencephalon-telencephalon boundary (DTB). In vitro, BIG1-deficient
neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also
hypersensitive to low dose glutamate (5 MUM), and died via apoptosis. This study
showed the role of BIG1 in the survival of DL neurons in developing embryonic
brain and in the generation of neuronal polarity.
PMID- 28414799
TI - Comprehensive evaluation of ten deformable image registration algorithms for
contour propagation between CT and cone-beam CT images in adaptive head & neck
radiotherapy.
AB - Deformable image registration (DIR) is a critical technic in adaptive
radiotherapy (ART) for propagating contours between planning computerized
tomography (CT) images and treatment CT/cone-beam CT (CBCT) images to account for
organ deformation for treatment re-planning. To validate the ability and accuracy
of DIR algorithms in organ at risk (OAR) contour mapping, ten intensity-based DIR
strategies, which were classified into four categories-optical flow-based, demons
based, level-set-based and spline-based-were tested on planning CT and fractional
CBCT images acquired from twenty-one head & neck (H&N) cancer patients who
underwent 6~7-week intensity-modulated radiation therapy (IMRT). Three similarity
metrics, i.e., the Dice similarity coefficient (DSC), the percentage error (PE)
and the Hausdorff distance (HD), were employed to measure the agreement between
the propagated contours and the physician-delineated ground truths of four OARs,
including the vertebra (VTB), the vertebral foramen (VF), the parotid gland (PG)
and the submandibular gland (SMG). It was found that the evaluated DIRs in this
work did not necessarily outperform rigid registration. DIR performed better for
bony structures than soft-tissue organs, and the DIR performance tended to vary
for different ROIs with different degrees of deformation as the treatment
proceeded. Generally, the optical flow-based DIR performed best, while the demons
based DIR usually ranked last except for a modified demons-based DISC used for CT
CBCT DIR. These experimental results suggest that the choice of a specific DIR
algorithm depends on the image modality, anatomic site, magnitude of deformation
and application. Therefore, careful examinations and modifications are required
before accepting the auto-propagated contours, especially for automatic re
planning ART systems.
PMID- 28414800
TI - Semantic prioritization of novel causative genomic variants.
AB - Discriminating the causative disease variant(s) for individuals with inherited or
de novo mutations presents one of the main challenges faced by the clinical
genetics community today. Computational approaches for variant prioritization
include machine learning methods utilizing a large number of features, including
molecular information, interaction networks, or phenotypes. Here, we demonstrate
the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies
and automated reasoning over genotype-phenotype relations to filter and
prioritize variants in whole exome and whole genome sequencing datasets. We
demonstrate the performance of PVP in identifying causative variants on a large
number of synthetic whole exome and whole genome sequences, covering a wide range
of diseases and syndromes. In a retrospective study, we further illustrate the
application of PVP for the interpretation of whole exome sequencing data in
patients suffering from congenital hypothyroidism. We find that PVP accurately
identifies causative variants in whole exome and whole genome sequencing datasets
and provides a powerful resource for the discovery of causal variants.
PMID- 28414801
TI - Probabilistic fluorescence-based synapse detection.
AB - Deeper exploration of the brain's vast synaptic networks will require new tools
for high-throughput structural and molecular profiling of the diverse populations
of synapses that compose those networks. Fluorescence microscopy (FM) and
electron microscopy (EM) offer complementary advantages and disadvantages for
single-synapse analysis. FM combines exquisite molecular discrimination
capacities with high speed and low cost, but rigorous discrimination between
synaptic and non-synaptic fluorescence signals is challenging. In contrast, EM
remains the gold standard for reliable identification of a synapse, but offers
only limited molecular discrimination and is slow and costly. To develop and test
single-synapse image analysis methods, we have used datasets from conjugate array
tomography (cAT), which provides voxel-conjugate FM and EM (annotated) images of
the same individual synapses. We report a novel unsupervised probabilistic method
for detection of synapses from multiplex FM (muxFM) image data, and evaluate this
method both by comparison to EM gold standard annotated data and by examining its
capacity to reproduce known important features of cortical synapse distributions.
The proposed probabilistic model-based synapse detector accepts molecular
morphological synapse models as user queries, and delivers a volumetric map of
the probability that each voxel represents part of a synapse. Taking human
annotation of cAT EM data as ground truth, we show that our algorithm detects
synapses from muxFM data alone as successfully as human annotators seeing only
the muxFM data, and accurately reproduces known architectural features of
cortical synapse distributions. This approach opens the door to data-driven
discovery of new synapse types and their density. We suggest that our
probabilistic synapse detector will also be useful for analysis of standard
confocal and super-resolution FM images, where EM cross-validation is not
practical.
PMID- 28414802
TI - Neuronal cell fate specification by the molecular convergence of different spatio
temporal cues on a common initiator terminal selector gene.
AB - The extensive genetic regulatory flows underlying specification of different
neuronal subtypes are not well understood at the molecular level. The Nplp1
neuropeptide neurons in the developing Drosophila nerve cord belong to two sub
classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1
neurons are specified by spatial cues; the Hox homeotic network and GATA factor
grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These
spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp
neurons that activate a common terminal selector feedforward cascade of col ->
ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1
neurons, and find that the cis-regulatory organization of col functions as an
integratory node for the different spatio-temporal combinatorial codes. These
findings may provide a logical framework for addressing spatio-temporal control
of neuronal sub-type specification in other systems.
PMID- 28414803
TI - New metric for optimizing Continuous Loop Averaging Deconvolution (CLAD)
sequences under the 1/f noise model.
AB - Continuous loop averaging deconvolution (CLAD) is one of the proven methods for
recovering transient auditory evoked potentials (AEPs) in rapid stimulation
paradigms, which requires an elaborated stimulus sequence design to attenuate
impacts from noise in data. The present study aimed to develop a new metric in
gauging a CLAD sequence in terms of noise gain factor (NGF), which has been
proposed previously but with less effectiveness in the presence of pink (1/f)
noise. We derived the new metric by explicitly introducing the 1/f model into the
proposed time-continuous sequence. We selected several representative CLAD
sequences to test their noise property on typical EEG recordings, as well as on
five real CLAD electroencephalogram (EEG) recordings to retrieve the middle
latency responses. We also demonstrated the merit of the new metric in generating
and quantifying optimized sequences using a classic genetic algorithm. The new
metric shows evident improvements in measuring actual noise gains at different
frequencies, and better performance than the original NGF in various aspects. The
new metric is a generalized NGF measurement that can better quantify the
performance of a CLAD sequence, and provide a more efficient mean of generating
CLAD sequences via the incorporation with optimization algorithms. The present
study can facilitate the specific application of CLAD paradigm with desired
sequences in the clinic.
PMID- 28414804
TI - Cyclosporine A alters expression of renal microRNAs: New insights into
calcineurin inhibitor nephrotoxicity.
AB - Calcineurin inhibitors are powerful immunosuppressants that revolutionized organ
transplantation. However, non-immune effects of the calcineurin inhibitor, such
as cyclosporine A (CsA), have significantly hindered their use. Specifically,
nephrotoxicity, which is associated with tubulointerstitial fibrosis,
inflammation, and podocyte damage, affects up to half of all transplant patients.
Calcineurin is involved in many aspects of kidney development and function;
therefore, mechanisms of CsA-induced nephrotoxicity are complex and not yet fully
understood. MicroRNAs are short non-coding RNAs that regulate protein-coding RNA
expression through post-translational repression of target messenger RNAs.
MicroRNA dysregulation is known to be involved in kidney diseases including
fibrosis. In this study, we compared the renal microRNA expression profiles
between mice that received CsA (20 mg/kg) or vehicle daily for six weeks. The
results demonstrate that CsA induces significant changes in renal microRNA
expression profile. We used combined criteria of False Discovery Rate (<=0.1),
fold change (>=2) and median signal strength (>=50) and identified 76
differencially expressed microRNAs. This approach identified microRNAs previously
linked to renal fibrosis that includes let-7d, miR-21, miR-29, miR-30, miR-130,
miR-192, and miR-200 as well as microRNAs that have not been reported to be
related to nephrotoxicity or immunosuppression. Pathway analysis of microRNA/mRNA
changes highlights the Wnt, TGF-beta, mTOR, and VEGF pathways. The mRNA
expression profiles were compared in the same samples. The change of mRNA and
microRNA profiles showed close correlations. To validate that the observed
microRNA and mRNA expression level changes in mice kidney tissue were directly
related to CsA treatment, the expression change induced by CsA treatment of three
microRNAs (miR-21, miR-186, and miR-709) and three mRNAs (BMPR1a, SMURF1 and
SMAD7) were compared in HEK293 cell line. A similar trend of expression level
change was induced by CsA treatment in all selected microRNAs and mRNAs in the in
vitro cell model. These data provide a roadmap for future work to study the role
of the known and novel candidate microRNAs in the mechanism of nephrotoxicity and
their further therapeutic potential.
PMID- 28414805
TI - Measurements of the parapapillary atrophy zones in en face optical coherence
tomography images.
AB - OBJECTIVE: To measure the parapapillary atrophy (PPA) area in en face images
obtained with swept-source optical coherence tomography (SS-OCT), and to evaluate
its relationship to glaucoma, myopia, and age in non-highly myopic subjects.
DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Fifty eyes of 30
subjects with open-angle glaucoma (G group) and forty-three eyes of 26 healthy
control subjects (C group). Eyes with high myopia (spherical equivalent
refractive error <= -8 diopters or axial length >= 26.5 mm) were excluded.
METHODS: Mean age +/- standard deviation was 59.9 +/- 12.4 years. The beta zone
and the gamma zone PPA areas were measured in en face images reconstructed from
three-dimensional SS-OCT images. Relationship between the PPA areas and patient
characteristics such as glaucoma, axial length, and age was statistically
evaluated using multivariate mixed-effects models. MAIN OUTCOME MEASURES: Areas
of the beta zone and the gamma zone PPA measured on en face OCT images. RESULTS:
Average +/- standard deviation area of the beta and the gamma zone was 0.64 +/-
0.79 and 0.16 +/- 0.30 mm2, respectively. In multivariate models, the gamma zone
significantly correlated with axial length (P = 0.001) but not with glaucoma (P =
0.944). In contrast, the beta zone significantly correlated with age (P = 0.0249)
and glaucoma (P = 0.014). CONCLUSIONS: En face images reconstructed from 3D SS
OCT data facilitated measurements of the beta and the gamma PPA zones even in
eyes with optic disc distortion. The OCT-defined beta zone is associated with
glaucoma and age, whereas the gamma zone correlated with myopia but not with
glaucoma. This study confirmed the clinical usefulness of OCT-based
classification of the PPA zones in distinguishing glaucomatous damage of the
optic nerve from myopic damage in non-highly myopic eyes.
PMID- 28414806
TI - Cost-effectiveness of nurse-led multifactorial care to prevent or postpone new
disabilities in community-living older people: Results of a cluster randomized
trial.
AB - OBJECTIVE: To evaluate the cost-effectiveness of nurse-led multifactorial care to
prevent or postpone new disabilities in community-living older people in
comparison with usual care. METHODS: We conducted cost-effectiveness and cost
utility analyses alongside a cluster randomized trial with one-year follow-up.
Participants were aged >= 70 years and at increased risk of functional decline.
Participants in the intervention group (n = 1209) received a comprehensive
geriatric assessment and individually tailored multifactorial interventions
coordinated by a community-care registered nurse with multiple follow-up visits.
The control group (n = 1074) received usual care. Costs were assessed from a
healthcare perspective. Outcome measures included disability (modified Katz
Activities of Daily Living (ADL) index score), and quality-adjusted life-years
(QALYs). Statistical uncertainty surrounding Incremental Cost-Effectiveness
Ratios (ICERs) was estimated using bootstrapped bivariate regression models while
adjusting for confounders. RESULTS: There were no statistically significant
differences in Katz-ADL index score and QALYs between the two groups. Total mean
costs were significantly higher in the intervention group (EUR 6518 (SE 472)
compared with usual care (EUR 5214 (SE 338); adjusted mean difference ?1457 (95%
CI: 572; 2537). Cost-effectiveness acceptability curves showed that the maximum
probability of the intervention being cost-effective was 0.14 at a willingness to
pay (WTP) of EUR 50,000 per one point improvement on the Katz-ADL index score and
0.04 at a WTP of EUR 50,000 per QALY gained. CONCLUSION: The current intervention
was not cost-effective compared to usual care to prevent or postpone new
disabilities over a one-year period. Based on these findings, implementation of
the evaluated multifactorial nurse-led care model is not to be recommended.
PMID- 28414807
TI - Interactions between the breast cancer-associated MUC1 mucins and C-type lectin
characterized by optical tweezers.
AB - Carbohydrate-protein interactions govern many crucial processes in biological
systems including cell recognition events. We have used the sensitive force probe
optical tweezers to quantify the interactions occurring between MGL lectins and
MUC1 carrying the cancer-associated glycan antigens mucins Tn and STn. Unbinding
forces of 7.6 pN and 7.1 pN were determined for the MUC1(Tn)-MGL and MUC1(STn)
MGL interactions, at a force loading rate of ~40 pN/s. The interaction strength
increased with increasing force loading rate, to 27 and 37 pN at a force loading
rate of ~ 310 pN/s. No interactions were detected between MGL and MUC1(ST), a
glycoform of MUC1 also expressed by breast carcinoma cells. Interestingly, this
glycan (ST) can be found on proteins expressed by normal cells, although in this
case not on MUC1. Additionally, GalNAc decorated polyethylene glycol displayed
similar rupture forces as observed for MUC1(Tn) and MUC1(STn) when forced to
unbind from MGL, indicating that GalNAc is an essential group in these
interactions. Since the STn glycan decoration is more frequently found on the
surface of carcinomas than the Tn glycan, the binding of MUC1 carrying STn to MGL
may be more physiologically relevant and may be in part responsible for some of
the characteristics of STn expressing tumours.
PMID- 28414808
TI - A longitudinal and experimental study of the impact of knowledge on the bases of
institutional trust.
AB - This study examined a knowledge-centered theory of institutional trust
development. In the context of trust in water regulatory institutions, the
moderating impact of knowledge was tested to determine if there were longitudinal
changes in the bases of institutional trust as a function of increases in
knowledge about a target institution. We hypothesized that as people learn about
an institution with which they were previously unfamiliar, they begin to form
more nuanced perceptions, distinguishing the new institution from other
institutions and relying less upon their generalized trust to estimate their
trust in that institution. Prior to having specific, differential information
about a new institution, we expected institutional trust to be a function of
generalized trust variables such as dispositional trust and trust in government.
The longitudinal experiment involved 185 college students randomly assigned to
one of three information conditions. Every 3 months for 15 months, participants
read information about water regulatory institutions or a control institution. At
each time point, participants reported their trust in and perceptions of the
trust- and distrust-worthiness of the water regulatory institutions. Participants
also completed measures of knowledge of water regulatory institutions,
dispositional trust, and governmental trust. Our manipulation check indicated
that, as expected, those in the experimental group increased in subjective
knowledge of water regulatory institutions to a greater extent than those in the
control condition. Consistent with our hypotheses, there was some evidence that,
compared to the control group, the experimental group relied less on their
general trust in government as a basis for their trust in water regulatory
institutions. However, contrary to our hypotheses, there was no evidence the
experimental group relied less on dispositional trust as a basis for
institutional trust. There also was some evidence the experimental group's trust
in water regulatory institutions was less affected by fluctuations of
trustworthiness (but not distrustworthiness) perceptions over time. This suggests
that knowledge results in the development of more stable institutional trust
attitudes, but that trustworthiness and distrustworthiness perceptions may
operate somewhat differently when impacting trust in specific institutions.
PMID- 28414810
TI - Changes in the effects of living with no siblings or living with grandparents on
overweight and obesity in children: Results from a national cohort study in
Japan.
AB - Effects of living without siblings and living with grandparents on overweight and
obesity may change with child's age. We aimed to examine these effects from early
childhood to school age at the national level in Japan. Subjects were 43,046
children born in Japan during two weeks in 2001 who were followed annually from
2.5 to 13 years of age in the Longitudinal Survey of Newborns in the 21st
Century. We used measured body height and weight reported by participants at each
survey and followed the criteria of the International Obesity Task Force to
define overweight and obesity. Random-effects logit models by sex, adjusted for
time-varying and time-invariant covariates, assessed odds ratios of overweight
and obesity for living without siblings and for living with grandparents at each
age. The likelihood of overweight and obesity was significantly higher at 8 years
and older among children living without siblings, compared with those living with
siblings, and odds ratios were highest at 11 years of age in boys (1.87, 95%
confidence interval [CI]: 1.49, 2.33) and at 10 and 13 years of age in girls
(1.75 [95% CI: 1.36, 2.23] and 1.73 [95% CI: 1.30, 2.31], respectively). It was
also significantly higher at 5.5 years and older among children living with
grandparents, compared with those living without grandparents, and odds ratios
were highest at 10 and 13 years of age in boys (1.53 [95% CI: 1.30, 1.80] and
1.54 [95% CI: 1.27, 1.86], respectively) and at 11 years of age in girls (1.51,
95% CI: 1.24, 1.84). In Japan, living without siblings and living with
grandparents may increase the likelihood of overweight and obesity at 8 and 5.5
years and older, respectively. Child's age should be considered during
formulation of strategies for prevention of overweight and obesity in these
groups.
PMID- 28414809
TI - Comparative expression profiling of testis-enriched genes regulated during the
development of spermatogonial cells.
AB - The testis has been identified as the organ in which a large number of tissue
enriched genes are present. However, a large portion of transcripts related to
each stage or cell type in the testis still remains unknown. In this study,
databases combined with confirmatory measurements were used to investigate testis
enriched genes, localization in the testis, developmental regulation, gene
expression profiles of testicular disease, and signaling pathways. Our
comparative analysis of GEO DataSets showed that 24 genes are predominantly
expressed in testis. Cellular locations of 15 testis-enriched proteins in human
testis have been identified and most of them were located in spermatocytes and
round spermatids. Real-time PCR revealed that expressions of these 15 genes are
significantly increased during testis development. Also, an analysis of GEO
DataSets indicated that expressions of these 15 genes were significantly
decreased in teratozoospermic patients and polyubiquitin knockout mice,
suggesting their involvement in normal testis development. Pathway analysis
revealed that most of those 15 genes are implicated in various sperm-related cell
processes and disease conditions. This approach provides effective strategies for
discovering novel testis-enriched genes and their expression patterns, paving the
way for future characterization of their functions regarding infertility and
providing new biomarkers for specific stages of spematogenesis.
PMID- 28414811
TI - Tissue expression profiles and transcriptional regulation of elongase of very
long chain fatty acid 6 in bovine mammary epithelial cells.
AB - In mammals, very long chain fatty acids (VLCFAs) perform pleiotropic roles in a
wide range of biological processes, such as cell membrane formation, cell signal
transduction, and endocrine regulation. Beef and milk are abundant of palmitic
acid which can be further elongated into stearic acid for synthesizing VLCFAs.
Elongase of very long chain fatty acid 6 (ELOVL6) is a rate-limiting enzyme for
converting palmitic acid to stearic acid. Consequently, investigating the tissue
expression patterns and transcriptional regulation of bovine ELOVL6 can provide
new insights into improving the composition of beneficial fats in cattle and
expanding the knowledge of transcriptional regulation mechanism among domestic
animals. In the current study, we found that bovine ELOVL6 expressed
ubiquitously. Dual-luciferase reporter assay identified that the core promoter
region (-130/-41 bp) was located in the second CpG island. In addition, the
deletion mutation of binding sites demonstrated that sterol regulatory element
binding transcription factor 1 (SREBF1) and specific protein 1 (SP1) both were
able to stimulate bovine ELOVL6 promoter activity independently, while resulting
the similar effect. To confirm these findings, further RNA interference assays
were executed in bovine mammary epithelial cells (BMECs). In summary, these data
suggest that bovine ELOVL6 expressed ubiquitously and is activated by SREBF1 and
SP1, via two binding sites present in the ELOVL6 promoter region between -130 bp
to -41bp.
PMID- 28414812
TI - Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and
vascular dysfunction in hyperhomocysteinemia.
AB - There is an emerging consensus that hyperhomocysteinemia is an independent risk
factor for cerebral vascular disease and that homocysteine-lowering therapy
protects from ischemic stroke. However, the mechanisms by which
hyperhomocysteinemia produces abnormalities of cerebral vascular structure and
function remain largely undefined. Our objective in this study was to define the
mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular
dysfunction and hypertrophy. Unlike previous studies, our experimental design
included a genetic approach to alter superoxide levels by using superoxide
dismutase 1 (SOD1)-deficient mice fed a high methionine/low folate diet to
produce hyperhomocysteinemia. In wild-type mice, the hyperhomocysteinemic diet
caused elevated superoxide levels and impaired responses to endothelium-dependent
vasodilators in cerebral arterioles, and SOD1 deficiency compounded the severity
of these effects. The cross-sectional area of the pial arteriolar wall was
markedly increased in mice with SOD1 deficiency, and the hyperhomocysteinemic
diet sensitized SOD1-deficient mice to this hypertrophic effect. Analysis of
individual components of the vascular wall demonstrated a significant increase in
the content of smooth muscle and elastin. We conclude that superoxide is a key
driver of both cerebral vascular hypertrophy and vasomotor dysfunction in this
model of dietary hyperhomocysteinemia. These findings provide insight into the
mechanisms by which hyperhomocysteinemia promotes cerebral vascular disease and
ischemic stroke.
PMID- 28414814
TI - An algorithm for separation of mixed sparse and Gaussian sources.
AB - Independent component analysis (ICA) is a ubiquitous method for decomposing
complex signal mixtures into a small set of statistically independent source
signals. However, in cases in which the signal mixture consists of both
nongaussian and Gaussian sources, the Gaussian sources will not be recoverable by
ICA and will pollute estimates of the nongaussian sources. Therefore, it is
desirable to have methods for mixed ICA/PCA which can separate mixtures of
Gaussian and nongaussian sources. For mixtures of purely Gaussian sources,
principal component analysis (PCA) can provide a basis for the Gaussian subspace.
We introduce a new method for mixed ICA/PCA which we call Mixed ICA/PCA via
Reproducibility Stability (MIPReSt). Our method uses a repeated estimations
technique to rank sources by reproducibility, combined with decomposition of
multiple subsamplings of the original data matrix. These multiple decompositions
allow us to assess component stability as the size of the data matrix changes,
which can be used to determinine the dimension of the nongaussian subspace in a
mixture. We demonstrate the utility of MIPReSt for signal mixtures consisting of
simulated sources and real-word (speech) sources, as well as mixture of unknown
composition.
PMID- 28414813
TI - DNA barcoding evaluation and implications for phylogenetic relationships in
Lauraceae from China.
AB - Lauraceae are an important component of tropical and subtropical forests and have
major ecological and economic significance. Owing to lack of clear-cut
morphological differences between genera and species, this family is an ideal
case for testing the efficacy of DNA barcoding in the identification and
discrimination of species and genera. In this study, we evaluated five widely
recommended plant DNA barcode loci matK, rbcL, trnH-psbA, ITS2 and the entire ITS
region for 409 individuals representing 133 species, 12 genera from China. We
tested the ability of DNA barcoding to distinguish species and as an alternative
tool for correcting species misidentification. We also used the rbcL+matK+trnH
psbA+ITS loci to investigate the phylogenetic relationships of the species
examined. Among the gene regions and their combinations, ITS was the most
efficient for identifying species (57.5%) and genera (70%). DNA barcoding also
had a positive role for correcting species misidentification (10.8%).
Furthermore, based on the results of the phylogenetic analyses, Chinese Lauraceae
species formed three supported monophyletic clades, with the Cryptocarya group
strongly supported (PP = 1.00, BS = 100%) and the clade including the Persea
group, Laureae and Cinnamomum also receiving strong support (PP = 1.00, BS =
98%), whereas the Caryodaphnopsis-Neocinnamomum received only moderate support
(PP = 1.00 and BS = 85%). This study indicates that molecular barcoding can
assist in screening difficult to identify families like Lauraceae, detecting
errors of species identification, as well as helping to reconstruct phylogenetic
relationships. DNA barcoding can thus help with large-scale biodiversity
inventories and rare species conservation by improving accuracy, as well as
reducing time and costs associated with species identification.
PMID- 28414815
TI - Isolation of human explant derived cardiac stem cells from cryopreserved heart
tissue.
AB - The value of preserving high quality bio specimens for fundamental research is
significant as linking cellular and molecular changes to clinical and
epidemiological data has fueled many recent advances in medicine. Unfortunately,
storage of traditional biospecimens is limited to fixed samples or isolated
genetic material. Here, we report the effect of cryopreservation of routine
myocardial biopsies on explant derived cardiac stem cell (EDC) culture outcomes.
We demonstrate that immediate cryopreservation or delayed cryopreservation after
suspension within cardioplegia for 12 hours did not alter EDC yields,
proliferative capacity, antigenic phenotype or paracrine signature.
Cryopreservation had negligible effects on the ability of EDCs to adopt a cardiac
lineage, stimulate new vessel growth, attract circulating angiogenic cells and
repair injured myocardium. Finally, cryopreservation did not influence the
ability of EDCs to undergo genetic reprogramming into inducible pluripotent stem
cells. This study establishes a means of storing cardiac samples as a retrievable
live cell source for cardiac repair or disease modeling.
PMID- 28414816
TI - Fourier transform power spectrum is a potential measure of tissue alignment in
standard MRI: A multiple sclerosis study.
AB - Loss of tissue coherency in brain white matter is found in many neurological
diseases such as multiple sclerosis (MS). While several approaches have been
proposed to evaluate white matter coherency including fractional anisotropy and
fiber tracking in diffusion-weighted imaging, few are available for standard
magnetic resonance imaging (MRI). Here we present an image post-processing method
for this purpose based on Fourier transform (FT) power spectrum. T2-weighted
images were collected from 19 patients (10 relapsing-remitting and 9 secondary
progressive MS) and 19 age- and gender-matched controls. Image processing steps
included: computation, normalization, and thresholding of FT power spectrum;
determination of tissue alignment profile and dominant alignment direction; and
calculation of alignment complexity using a new measure named angular entropy. To
test the validity of this method, we used a highly organized brain white matter
structure, corpus callosum. Six regions of interest were examined from the left,
central and right aspects of both genu and splenium. We found that the dominant
orientation of each ROI derived from our method was significantly correlated with
the predicted directions based on anatomy. There was greater angular entropy in
patients than controls, and a trend to be greater in secondary progressive MS
patients. These findings suggest that it is possible to detect tissue alignment
and anisotropy using traditional MRI, which are routinely acquired in clinical
practice. Analysis of FT power spectrum may become a new approach for advancing
the evaluation and management of patients with MS and similar disorders. Further
confirmation is warranted.
PMID- 28414817
TI - Correction: Assessment of Universal Healthcare Coverage in a District of North
India: A Rapid Cross-Sectional Survey Using Tablet Computers.
AB - [This corrects the article DOI: 10.1371/journal.pone.0157831.].
PMID- 28414818
TI - TGFbeta/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in
colon cancer cells.
AB - In this study, we have uncovered a novel crosstalk between TGFbeta and IGF-1R
signaling pathways. We show for the first time that expression and activation of
IRS-1, an IGF-1R adaptor protein, is decreased by TGFbeta/Smad3 signaling. Loss
or attenuation of TGFbeta activation leads to elevated expression and
phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell
proliferation, decreased apoptosis and increased tumor growth in vitro and in
vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated
oncogenic phenotypes, indicating that TGFbeta/Smad3 signaling inhibits cell
proliferation and increases apoptosis at least partially through the inhibition
of IRS-1 expression and activation. Additionally, the TGFbeta/Smad3/IRS-1
signaling axis regulates expression of cyclin D1 and XIAP, which may contribute
to TGFbeta/Smad3/IRS-1-mediated cell cycle progression and survival. Given that
loss of TGFbeta signaling occurs frequently in colon cancer, an important
implication of our study is that IRS-1 could be a potential therapeutic target
for colon cancer treatment.
PMID- 28414819
TI - Glycemic markers and relation with arterial stiffness in Caucasian subjects of
the MARK study.
AB - BACKGROUND: Effect of prediabetes and normal glucose on arterial stiffness
remains controversial. The primary aim of this study was to investigate the
relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and
glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV)
and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was
to analyse this relationship by glycaemic status. METHODS: Cross-sectional study.
Setting: Primary care. Participants: 2,233 subjects, 35-74 years. Measures: FPG
(mg/dL) and HbA1c (%) of all subjects were measured using standard automated
enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals
(breakfast, lunch and dinner) for one day using an Accu-chek (r) glucometer. CAVI
was measured using a VaSera VS-1500(r) device (Fukuda Denshi), and baPWV was
calculated using a validated equation. RESULTS: CAVI and baPWV values were
significantly higher in subjects with diabetes mellitus than in glucose normal
and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated
with CAVI and baPWV. The beta regression coefficient for: HbA1c was 0.112 (CI 95%
0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was
0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with
baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to
0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status,
FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with
type 2 diabetes mellitus. CONCLUSION: FPG, PG and HbA1c show a positive
association with CAVI and baPWV, in Caucasian adults with intermediate
cardiovascular risk factors. When analysing by hyperglycaemic status, the
association is only maintained in subjects with type 2 diabetes mellitus. TRIAL
REGISTRATION: Clinical Trials.gov Identifier: NCT01428934. Registered 2 September
2011. Retrospectively registered. Last updated September 8, 2016.
PMID- 28414820
TI - Transcriptome analysis of the epidermis of the purple quail-like (q-lp) mutant of
silkworm, Bombyx mori.
AB - A new purple quail-like (q-lp) mutant found from the plain silkworm strain 932VR
has pigment dots on the epidermis similar to the pigment mutant quail (q). In
addition, q-lp mutant larvae are inactive, consume little and grow slowly, with a
high death rate and other developmental abnormalities. Pigmentation of the
silkworm epidermis consists of melanin, ommochrome and pteridine. Silkworm
development is regulated by ecdysone and juvenile hormone. In this study, we
performed RNA-Seq on the epidermis of the q-lp mutant in the 4th instar during
molting, with 932VR serving as the control. The results showed 515 differentially
expressed genes, of which 234 were upregulated and 281 downregulated in q-lp.
BLASTGO analysis indicated that the downregulated genes mainly encode protein
binding proteins, membrane components, oxidation/reduction enzymes, and
proteolytic enzymes, whereas the upregulated genes largely encode cuticle
structural constituents, membrane components, transport related proteins, and
protein-binding proteins. Quantitative reverse transcription PCR was used to
verify the accuracy of the RNA-Seq data, focusing on key genes for biosynthesis
of the three pigments and chitin as well as genes encoding cuticular proteins and
several related nuclear receptors, which are thought to play key roles in the q
lp mutant. We drew three conclusions based on the results: 1) melanin, ommochrome
and pteridine pigments are all increased in the q-lp mutant; 2) more cuticle
proteins are expressed in q-lp than in 932VR, and the number of upregulated
cuticular genes is significantly greater than downregulated genes; 3) the
downstream pathway regulated by ecdysone is blocked in the q-lp mutant. Our
research findings lay the foundation for further research on the developmental
changes responsible for the q-lp mutant.
PMID- 28414821
TI - Constructing a biodiversity terminological inventory.
AB - The increasing growth of literature in biodiversity presents challenges to users
who need to discover pertinent information in an efficient and timely manner. In
response, text mining techniques offer solutions by facilitating the automated
discovery of knowledge from large textual data. An important step in text mining
is the recognition of concepts via their linguistic realisation, i.e., terms.
However, a given concept may be referred to in text using various synonyms or
term variants, making search systems likely to overlook documents mentioning less
known variants, which are albeit relevant to a query term. Domain-specific
terminological resources, which include term variants, synonyms and related
terms, are thus important in supporting semantic search over large textual
archives. This article describes the use of text mining methods for the automatic
construction of a large-scale biodiversity term inventory. The inventory consists
of names of species, amongst which naming variations are prevalent. We apply a
number of distributional semantic techniques on all of the titles in the
Biodiversity Heritage Library, to compute semantic similarity between species
names and support the automated construction of the resource. With the
construction of our biodiversity term inventory, we demonstrate that
distributional semantic models are able to identify semantically similar names
that are not yet recorded in existing taxonomies. Such methods can thus be used
to update existing taxonomies semi-automatically by deriving semantically related
taxonomic names from a text corpus and allowing expert curators to validate them.
We also evaluate our inventory as a means to improve search by facilitating
automatic query expansion. Specifically, we developed a visual search interface
that suggests semantically related species names, which are available in our
inventory but not always in other repositories, to incorporate into the search
query. An assessment of the interface by domain experts reveals that our query
expansion based on related names is useful for increasing the number of relevant
documents retrieved. Its exploitation can benefit both users and developers of
search engines and text mining applications.
PMID- 28414822
TI - 2-dimensional shear wave elastography: Interobserver agreement and factors
related to interobserver discrepancy.
AB - PURPOSE: To evaluate the interobserver reproducibility of two-dimensional shear
wave elastography (2D-SWE) in measuring liver stiffness (LS) and to investigate
factors related to liver 2D-SWE. MATERIALS AND METHODS: A prospective study was
conducted between August 2011 and August 2012 in rheumatoid arthritis patients
who had been treated with methotrexate. Interobserver reproducibility of 2D-SWE
was evaluated, and the relationship between interobserver difference in LS and
related factors was analyzed using linear regression analyses. We considered age,
sex, alanine transaminase, cholesterol, body mass index (BMI), and waist
circumference as clinical factors, and the mean value of standard deviation
(SDM), its difference between two examiners, mean diameter of the regions of
interest (ROIM), and its difference in the elasticity map as investigation
factors. The cut-off value for significant factors to predict interobserver
discrepancies in LS-based fibrosis stage was also inspected. RESULTS: In total,
176 patients were enrolled. The intraclass correlation coefficient between the
two examiners was 0.784. In the univariate analysis, SDM and ROIM were
independently associated with interobserver differences in LS as well as BMI,
waist circumference, and the difference of ROI, but SDM and ROIM were the only
ones significantly related in multivariate analysis (p<0.001 and p = 0.021,
respectively). The best cut-off value for SDM in predicting interobserver
discrepancy in LS-based fibrosis stage was 1.4. CONCLUSIONS: Interobserver
reproducibility of 2D-SWE for measuring LS was good and SDM was the most
significantly associated factor with interobserver differences in LS and
interobserver discordance in LS-based fibrosis stage.
PMID- 28414824
TI - [Sociology and health: new developments and pending challenges].
PMID- 28414823
TI - Comparing in vitro and in vivo virulence phenotypes of Burkholderia pseudomallei
type G strains.
AB - Burkholderia pseudomallei (Bpm) is a saprophytic rod-shaped gram-negative
bacterium and the causative agent of melioidosis. This disease has previously
been described as endemic in areas such as northern Australia and Southeast Asia,
but, more recently, a better understanding of the epidemiology of melioidosis
indicated that the disease is distributed worldwide, including regions of the
Americas and Africa. A 16S-23S rDNA internal transcribed spacer (ITS) typing
system has been developed for Bpm and has revealed that ITS types C, E, and
hybrid CE are mainly associated with Australia and Southeast Asia while type G
strains are more associated with cases of melioidosis in the Western Hemisphere.
The purpose of the current study was to determine the in vitro and in vivo
virulence profiles of the understudied Bpm type G strains Ca2009, Ca2013a,
Mx2013, and 724644 and compared such phenotypes to the commonly studied Bpm type
C strain K96243. We evaluated virulence by measuring invasion/uptake and survival
of these Bpm strains in murine respiratory epithelial LA-4 cells and alveolar
macrophage MH-S cells using different multiplicity of infections (MOIs of 1 and
10). We also calculated the lethal dose 50 values (LD50) in BALB/c mice that were
inoculated intranasally with either Ca2009, Ca2013a, or Mx2013. Overall, the
virulence and lethality phenotypes of Bpm type G strains were similar to the Bpm
type C strain K96243. Additional comparative analyses between the Bpm ITS types
may lead to a better understanding of the contribution of the ITS type to the
epidemiology and ecology of Bpm strains.
PMID- 28414826
TI - [Tensions between the (il)legal and the (il)legitimate in professional health
practices regarding women who seek abortion].
AB - The implementation of a pre- and post-abortion health care strategy, adopted in
2004 in Uruguay within a restrictive legal context prior to the decriminalization
of abortion in 2012, opened a window of opportunity to link women facing unwanted
pregnancies and abortion to health services in order to prevent unsafe abortion
practices. This article looks into the tensions generated by the change of focus
from maternal-child health to health and sexual and reproductive rights, and how
those tensions operate. Using semi-structured interviews and focus groups, the
practices and perception and assessment frameworks of professionals in their care
of women facing unwanted pregnancy and abortion in the National Integrated Health
System in Montevideo are analyzed. The results offer insights into some of the
barriers and difficulties that can currently be observed in the implementation of
the new law.
PMID- 28414825
TI - [Medical power and the crisis in bonds of trust within contemporary medicine].
AB - Based on the Brazilian context, this paper addresses medical power in terms of
the current conflicts in the intersubjective relationships that doctors establish
in their work, conflicts considered here as a product of a crisis of trust
connected to recent historical transformations in the medical practice. Reading
these conflicts as questions of an ethical and moral order, we use Hanna Arendt's
theoretical formulations to further analyze this crisis of trust. In this way,
utilizing the concepts of "crisis," "tradition," "power," "authority," and
"natality," we search for new meanings regarding these conflicts, enabling new
paths and solutions that avoid nostalgia for the past.
PMID- 28414827
TI - [The temporal dimension of drugs: a sociological analysis based on a category key
to the study of health-disease-care processes].
AB - The temporal dimensions that shape the senses and practices of men and women who
are poly-consumers of psychoactive substances, 18-35 years of age, and living in
the metropolitan area of Buenos Aires were analyzed. Using a qualitative
approach, 29 individual in-depth interviews were carried out and then analyzed
through a constant comparative analysis process between the categories generated
from the data obtained and the theoretical concepts. From the analysis, practices
and meanings emerge that regulate the diverse temporalities that underlie drug
consumption: feelings related to body rhythms, periods between consumptions, the
timing of phases of the life cycle, or unspecific temporalities that become an
adequate "moment" for consumption. These practices require that particular
attention be paid to time, as this enables the flexibility to consume without
being a consumer, to use drugs without being addicted to them.
PMID- 28414828
TI - [The agribusiness industry in northwestern Mexico and the health of female
farmworkers: a proposal for study].
AB - This article seeks to outline the structure of the export-oriented agribusiness
industry in northwestern Mexico, so as to analyze the conditions of vulnerability
of female farmworkers in terms of their access to health services and the medical
attention they receive. Using a qualitative approach, focus groups and interviews
were carried out with farmworkers and subject experts pertaining to academia and
civil society. Their narratives were then analyzed using Pierre Bourdieu's
concept of field. The primary results demonstrate a lack of access to health
services and social security, and describe the main actors and their positions
with respect to the vulnerability of this population.
PMID- 28414829
TI - [From sociology in medicine to the sociology of collective health: contributions
toward a necessary reflexivity].
AB - This text looks at the difference between sociology in medicine (collaborator of
health institutions) and the sociology of medicine (independent of health
institutions). If consistent, sociology in medicine should become a sociology of
medicine. As an example, it is shown how the study of the social determinants of
health and illness begins by assuming non-problematically the ontological reality
of health and illness, but ends up problematizing the very concept of health
disease, demonstrating that the study of health determinants also requires the
study of the determinants of the social construction of disease. The urgent
necessity of objectifying collective health itself is argued. By applying
sociological tools we can examine the so-called objective factors in the
determination of health and disease, the socially constructed nature of these
categories of knowledge, and the struggles and power relations that determine
whether or not such categories are viable.
PMID- 28414830
TI - [Prevalence and evolution of helmet use in motorcycle riders in an Argentine city
(Mar del Plata, 2006-2014)].
AB - Traffic collisions involving motorcyclists are a growing problem in low and
middle income countries. Helmet use is the foremost protective measure for this
group of road users, however many riders do not wear them. The objective of the
present study is to report the changes in helmet use during the period 2006-2014
in an Argentine city and discover associated factors for the year 2014. The
sample includes more than 6,900 observations of motorcyclists carried out during
the years 2006 (n=962), 2008 (n=977), 2012 (n=2,542), and 2014 (n=2,466). The
data indicates a progressive increase in helmet use over time, but differences
due to gender and type of rider remain. Factors associated to helmet use in
motorcycle drivers during 2014 were: passenger helmet use, motorcycle type,
license plate use and gender. Although the results are positive, it is necessary
to be attentive to the negative consequences of the growing fleet of motorcycles.
PMID- 28414831
TI - [Child nutritional status in contexts of urban poverty: a reliable indicator of
family health?]
AB - This work questions the premise that the nutritional status of children under six
years of age is a reliable indicator of family health. To do so, a research
strategy based in case studies was carried out, following a qualitative design
(participant observation and semistructured interviews using intentional
sampling) and framed within the interpretivist paradigm. The anthropometric
measurements of 20 children under six years of age attending the local Child Care
Center in Villa La Tela, Cordoba were evaluated. Nutritional status was
understood as an object that includes socially determined biological processes,
and was therefore posited analytically as a cross between statistical data and
its social determination. As a statistic, child nutritional status is merely
descriptive; to assist in the understanding of its social determination, it must
be placed in dialectical relationship with the spheres of sociability proposed to
analyze the reproduction of health problems.
PMID- 28414832
TI - [Integrality in the health care perspective: an experience of the Unified Health
System in Brazil].
AB - Starting with a discussion of the biomedical model and its implications in the
shaping of healthcare professionals and health practices, this article analyzes
the concept of integrality as associated with the Unified Health System (SUS)
[Sistema Unico de Salud] in Brazil. Particular attention is paid to the disputes
regarding the meaning of integrality and the ways of putting the concept into
practice in everyday health care work. Based in a research study conducted at the
national level, the authors suggest two aspects crucial to fostering integrality:
an ethical-political project founded in the recognition that other people's lives
are worthwhile and enriching; as well as the existence of additional spaces
conducive to discovering diverse ways of producing life, in which integrality in
health care is also possible and powerful. The authors affirm the relevance of
this process as a contribution to the continual construction of the SUS in
Brazil.
PMID- 28414833
TI - [Concentration and inequalities in the financing of obras sociales after
deregulation: a comparative analysis of the years 2004 and 2011].
AB - In Argentina, during the decade of the 1990s major changes were introduced into
the regulatory framework of the national obras sociales, or union-based health
coverage plans. Using data from the Federal Administration of Public Income
(AFIP) [Administracion Federal de Ingresos Publicos], this study evaluates for
the years 2004 and 2011: a) the importance of obras sociales within the
healthcare system, b) the degree of concentration of this health social security
subsystem, and c) the inequalities in the availability of funds among the obras
sociales and their beneficiaries. The results show an increased importance of
obras sociales within the Argentine health system. The concentration of funds
distributed to the most important institutions within the subsystem showed no
change, while the concentration of contributors to these institutions slightly
increased and that of beneficiaries decreased. Finally, a reduction of the
inequalities in funds per beneficiary received by different institutions was
observed. This trend can be explained, among other factors, by the attenuation of
wage differentials between branches of economic activity and the actions of the
so-called Solidarity Redistribution Fund.
PMID- 28414834
TI - [Salud Colectiva: taking a stand in favor of open access].
PMID- 28414835
TI - [Thinking about health once again: programs and territories].
AB - This article, of a conceptual nature, uses critical theory to discuss the
programmatic logic within the sociosanitary field as a technical answer without
any questions, provided to territories or spaces with questions awaiting
translation. The purpose is to put programmatic logic, which is the legacy of
public health planning and an expression of instrumental reason, into discussion,
and in this way examine the temporal-spatial conception as an axis for thinking
and acting within the complexity of the social world, recognizing other knowledge
and practices. The questions, answers, knowledge and actions in the sociosanitary
field constitute the focus of a reflection rooted in concepts that seek to
deconstruct the ideological project represented by health programs through an
analysis of their scientific basis (the epistemological component of the
technical), which is antagonistic to any emancipatory project.
PMID- 28414836
TI - [An ethnographic approach to the concepts of health and disease in the Turkana
tribe: a project to improve the health of the nomads of the Ilemi Triangle,
Kenya].
AB - This paper aims to provide a broad view of the Turkana tribe of the Ilemi
Triangle in northwestern Kenya, especially regarding the way the members of this
nomadic ethnic group understand and shape their own construct of health and
disease. It is based in an ethnographic study carried out in July and August
2014, including participant observation of 15 villages of the Turkana tribe,
formal interviews and in-depth interviews carried out with the collaboration of
two translators of the tribe and a nurse. Field notes as well videos and audio
records were captured and transcribed for later analysis. Among the primary
results of this study, it should be highlighted that the concepts of both health
and disease differ greatly from the western approach that external projects bring
with them a priori and it is likely that the lack of adherence to these projects
is related to the scant cultural knowledge regarding such constructs on the part
of the health professionals.
PMID- 28414837
TI - [The representation of health care services in Mexican television: potential
consequences for health subjectivities].
AB - The objective of this paper is to analyze the representation of health services
in Mexican television, considering that television plays an important role in the
production and reproduction of the social meanings of health. A descriptive study
analyzed the contents of 672 hours of continuous television (media flows)
broadcast in Mexico in 2011, examining advertising, television shows and
newscasts. The analysis of all these messages shows that the representation of
private care services predominates. When public care services are mentioned, the
communication is mainly regarding the Seguro Popular de Salud [Popular Health
Insurance, for those with low incomes], while the social security model of care
is underrepresented. We therefore conclude that television favors the two first
models of health care. This kind of representation could hold potential
consequences for health subjectivities.
PMID- 28414838
TI - [Health and working conditions of high school and university teachers in Mendoza:
between commitment and emotional distress].
AB - With the objective of analyzing aspects related to the perception of working
conditions and their impact on health in the teachers and professors who work for
the Universidad Nacional de Cuyo (UNCuyo) in Mendoza, Argentina, this work
analyzes the results of the Primer Censo de Condiciones y Salud Laboral [First
Census on Health and Working Conditions]. The census was conducted in late 2013
in two academic units (one at the high school level and the other at the
university level), including 193 educators. The exploration set out to
characterize the teaching staff and the conditions affecting their health,
primarily with respect to psycho-social health. In order to do, so a self
administered questionnaire was applied, the dimensions of which were discussed in
sensitivity workshops with educators who helped to formulate the data collection
instrument. Among the primary results emerge the physical and emotional burnout
of these highly skilled workers, owing to the combined effect of their committed
response to the demands of their work and the deterioration (both material and
symbolic) of the conditions in which they carry out that work.
PMID- 28414839
TI - [The configuration of nursing labor conditions in the Buenos Aires Metropolitan
Area: An analysis at the intersection of the gender order and the organization of
the health system].
AB - The article explores two key factors which contribute to shape the poor working
conditions of nursing in Argentina. A first objective focuses on exploring the
effect of the occupation's care component, closely associated with cultural
images of "inherent" female qualities, on working conditions. A second objective
aims to examine the way in which the organization of health services provision in
Argentina intensifies the vulnerability of this occupation. Regarding the
methodology, the fieldwork conducted in the Metropolitan Area of Buenos Aires
included in-depth interviews with key informants and group interviews with
nurses. Among the results, on the one hand it is shown how the social devaluation
of care is reflected in the discourse of those who perform the occupation as well
as in institutional practices and policies in the health sector. On the other
hand, it is shown that the decentralization and fragmentation of the health
system act as additional obstacles hampering the articulation of labor demands.
PMID- 28414840
TI - [Quali-quantitative study of nutritional status and eating patterns in children
aged 1-3 years from low-income families in two population groups with different
productive activities (Buenos Aires, Argentina), 2007-2008].
AB - The aim of this article is to describe the nutritional status and eating patterns
of children aged 1-3 years from low-income families who reside in areas with
different productive activities: primary production and production of goods and
services. A descriptive cross-sectional study was performed with a qualitative
and quantitative methodology, evaluating anthropometric and biochemical
nutritional status, food intake, economic and demographic characteristics,
dietary practices and representations. The results show that children from areas
of primary production had a lower prevalence of anemia and iron deficiency. They
also had a higher consumption of energy, calcium, zinc, vitamin A and protein and
a greater diversity and quality in food consumption. We can conclude that the
geographical context of families closer to sources of primary production favors
interaction with individuals outside of the family, expanding both the informal
social network and access to better quality nutritional food.
PMID- 28414841
TI - [Analysis of the trend and impact of mortality due to external causes: Mexico,
2000-2013].
AB - The objective of this study was to analyze mortality due to the main external
causes of death (traffic accidents, other accidents, homicides and suicides) in
Mexico, calculating the years of life lost between 0 and 100 years of age and
their contribution to the change in life expectancy between 2000 and 2013, at the
national level, by sex and age group. Data came from mortality vital statistics
of the Instituto Nacional de Estadistica y Geografia (INEGI) [National Institute
of Statistics and Geography]. The biggest impact in mortality due to external
causes occurred in adolescent and adult males 15-49 years of age; mortality due
to these causes remained constant in males and slightly decreased in females.
Mortality due to traffic accidents and other accidents decreased, with a positive
contribution to life expectancy, but this effect was canceled out by the increase
in mortality due to homicides and suicides. Mortality due to external causes can
be avoided through interventions, programs and prevention strategies as well as
timely treatment. It is necessary to develop multidisciplinary studies on the
dynamics of the factors associated with mortality due to these causes.
PMID- 28414842
TI - [The challenge of inclusion in mental health: an analysis of a community center
and its work with social bonds].
AB - Social inclusion is a key component of transformations in mental health care,
because it takes into account the benefits of community life for both those with
mental illness and the other members of the community. In order to understand the
scope of inclusion within mental health, 45 participants of a community center
linked to a psychiatric hospital discharge program which explicitly seeks to
provide social inclusion were interviewed. The possible changes in social
relationships between users and other community members based in their sustained
daily interactions in the community center were explored. Results suggest that
the building of social bonds, as part of informal support networks, is one of the
benefits of attending the community center. Positive changes in ideas regarding
people with "mental illness" were also observed, although these ideas seemed to
be more connected to the notion of integration than to social inclusion.
PMID- 28414844
TI - [Contextualized editorial practices: Carlos Augusto Monteiro and the journal
Revista de Saude Publica].
AB - This text is part of a series of interviews that seek to explore diverse editing
and publication experiences and the similar difficulties Latin America journals
face, in order to begin to encounter contextualized solutions that articulate
previously isolated efforts. In this interview, carried out in July 2015 in the
Instituto de Salud Colectiva [Institute of Collective Health] of the Universidad
Nacional de Lanus, Carlos Augusto Monteiro speaks to us about funding, work
processes, technological innovations, and establishing teams and roles. He
analyzes the importance of Latin American journals as a platform for spreading
research relevant to national agendas, and the connection between journal
performance, the quality of graduate training programs and research quality.
PMID- 28414843
TI - [Violence in social networks: an exploration of the online expressions of teens
from marginalized areas of Greater Buenos Aires].
AB - This paper explores the online expressions of violence perpetrated or experienced
by adolescents from marginalized areas of Greater Buenos Aires, Argentina. Using
a qualitative methodology, four specific events were examined: threats, "bondis"
[fights], cyberbullying and displays of mourning. To do so, 20 in-depth
interviews and 3,000 virtual observations of profiles in the social network
Facebook were carried out. Among the main results, it was seen that most
expressions of violence are part of an offline-online dynamic. Empirical evidence
is also offered based upon which it can be affirmed that the expressions of
violence of these teenagers are developed around the culture of "aguante" [fierce
loyalty]. The article ponders the extent to which, in the iconic platform of the
option "like," these expressions are implicitly functional to the social network
or, to the contrary, or whether they allow displacements and significant
reappropriations on the part of users. New questions arise about the use of these
tools by adolescents from marginalized areas and the need for more complex
approaches to examine these phenomena.
PMID- 28414845
TI - [Contributions towards an "essential" medicine strategy for Latin America].
PMID- 28414846
TI - Clinical trials in Latin America: implications for the sustainability and safety
of pharmaceutical markets and the wellbeing of research subjects.
AB - This study sought to verify whether drugs approved by the US Food and Drug
Administration (FDA) were registered, commercialized and sold at affordable
prices in the Latin American countries where they had been tested, as well as to
ascertain their contribution to the quality of the pharmaceutical market. The
list of New Molecular Entities (NMEs) approved by the FDA in 2011 and 2012 was
consulted to determine the countries where pivotal trials were conducted.
Affordability was assessed as a proportion of income and information on safety
and efficacy was gathered from independent drug bulletins. In the study years, 33
medications were tested in 12 Latin American countries. Only 60% of the expected
registrations had been completed by September 2014. With one exception, all
products for which pricing information was obtained (n=18) cost more than one
monthly minimum wage in all countries. Only five drugs were classified as "could
be better than available treatments." Just one of the NMEs responds to the health
care priorities in low and middle income countries.
PMID- 28414847
TI - [Collective health in Brazil: analyzing the institutionalization process].
AB - This work first analyzes the construction of a typology of the studies on
collective health and its institutionalization process in Brazil, in which three
stages are proposed: the preventive project, social medicine and collective
health. Secondly, the work examines the phases of institutionalization,
disciplinarization and professionalization of collective health in Brazil. Within
the institutionalization phase, the study analyzes connectivity and
communication, regularization of discourses and practices, the construction of a
separate identity and political actions, and the incorporation and legitimation
of these elements. It is concluded that the trajectory of the construction of
collective health is marked by three dimensions: the theoretical-critical, the
political-sanitary and the pedagogical-professional.
PMID- 28414848
TI - [Abstract bodies, concrete risks: clinical devices and the health of ova donors
in Argentine reproductive medicine].
AB - Using a methodological perspective grounded in science and technology studies,
this article analyzes two sociotechnical devices used in Argentine reproductive
medicine (biostatistical measures and donation registries) with the aim of
controlling both the so-called "genetic risk" arising from the use of donated ova
as well as the health risks to female donors. By examining how the deployment of
monitoring criteria disregards the specificity of ova donation, the article
suggests that it is not the absence of control measures and clinical criteria
that produces an inadequate monitoring of such risks, but rather the concrete
ways in which such measures are implemented that results in potential harms to
the health of female donors.
PMID- 28414849
TI - [The rights of the dying: the refusal of medical treatments in Argentine courts].
AB - This paper addresses the judicialization of end of life medical decision-making,
as part of the advance of the justice system in the regulation of medical
practice and the rise of recognition of patient autonomy. The article analyzes,
from a sociological standpoint, legal decisions regarding treatment refusal at
the end of life produced by the Argentine courts between 1975 and 2015. Based on
a qualitative design, 38 sentences collected from jurisprudential databases using
key terms were analyzed. First, judicialized cases during the period are
described; these are characterized by a high proportion of claims presented by
health institutions, a pro-treatment bias in the legal actions requested, and a
high percentage of unnecessary litigation in the absence of conflicts or in
situations that do not require court intervention. Second, legal and extralegal
factors affecting the justiciability of decisions to refuse or withdraw medical
treatments, such as changes in the law and processes of politicization of claims,
are analyzed.
PMID- 28414850
TI - [Water resource quality as related to economic activity and health patterns in
Sonora, Mexico].
AB - The aim of this work is to analyze the spatial distribution of potential
pollution pathways of water resources given the economic activity in the Mexican
border state of Sonora and propose a regional distribution in relation to cancer
mortality rates across the state. The methodology is based in an exploratory and
inferential data analysis using two sources of primary data: wastewater discharge
concessions registered in the Public Registry on Water Rights [Registro Publico
de Derechos de Agua] (REPDA) and the records generated by the National Health
Information System [Sistema Nacional de Informacion en Salud] (SINAIS) in the
period 1998-2011 based on the International Classification of Disease (ICD-10).
The spatial concentration analysis allows for the identification of specific
cancer mortality causes at the regional level. Results indicate that the
projected adjustments to the regulation NOM-250-SSA1-2014, which controls a
subset of pollutants common in mining activity surroundings, is a matter of
regional concern.
PMID- 28414851
TI - [Bilingual guides: a strategy to decrease cultural barriers to health care access
in the Wayuu communities of Maicao, Colombia].
AB - The article examines the use of bilingual guides to decrease cultural barriers to
health care access in the Wayuu indigenous communities of Colombia. Within a
larger project on HIV carried out between 2012 and 2014, 24 interviews were
conducted with key actors in the administrative and health areas, including Wayuu
bilingual guides. As a result of the qualitative analysis, the study identified
three cultural barriers to health care access: a) language; b) the Wayuu
worldview regarding the body, health, and illness; and c) information about
sexual and reproductive health and HIV not adapted to the Wayuu culture. The
study identifies the bilingual guides as key actors in reducing these barriers
and concludes with a discussion of the role of the guides, the tensions inherent
to their work, and the complexity of their contributions as cultural mediators.
PMID- 28414853
TI - [Excessive osteoporosis screening in women under 65 years: a cross-sectional
study].
AB - Overuse of osteoporosis screening in women at low risk of fracture may lead to
overdiagnosis, inappropriate treatment and medicalization. The objective of this
work was to estimate the proportion of women aged 45 to 64 enrolled in a private
health insurance plan in Buenos Aires undergoing hip dual-energy x-ray
absorptiometry (DXA) in 2011 without meeting osteoporosis screening criteria. In
this cross-sectional study, 4310 women of this age range that had undergone a hip
DXA were identified. A randomly selected sub-group of 401 women was then assessed
for the presence of risk factors for osteoporosis and complete data were
retrieved for 178 women. Appropriate screening was defined by two criteria: 1)
having a 10-year fracture risk higher than that of a 65-year old woman (estimated
using the FRAX(r) tool); 2) having at least one risk factor for fracture. It was
found that 86.5% of the women who underwent hip DXA did not exceed the minimum 10
year fracture risk threshold required for screening; 5.8% of them had
osteoporosis and 61.0% osteopenia. According to the second criterion, 49.4% had
no risk factors, 3.4% of these women had osteoporosis and 62.5% osteopenia. The
results show that at least half the women screened did not meet osteoporosis
screening criteria.
PMID- 28414852
TI - [Access to oral health services in children under twelve years of age in Peru,
2014].
AB - The aim of the study was to explore the patterns of dental health services access
in children under twelve years of age in Peru. Data from 25,285 children under 12
years who participated in the Demographic and Family Health Survey of 2014 were
reviewed. An exploratory spatial analysis was performed to project the
proportions of children with access to dental health services, according to
national regions, type of health service and urban or rural place of residence.
The results show that of the total sample, 26.7% had access to dental health
services in the last six months, 39.6% belonged to the age group 0-4 years, 40.6%
lived in the Andean region and 58.3% lived in urban areas. The regions of
Huancavelica, Apurimac, Ayacucho, Lima and Pasco had the highest percentages of
access nationwide. In conclusion, there is low access to dental health services
in the population under 12 years of age in Peru. The spatial distribution of
access to dental health services allows regions to be identified and grouped
according to similar access patterns, in order to better focus public health
actions.
PMID- 28414854
TI - [Contextualized editorial practices: Maria Cecilia de Souza Minayo and the
journal Ciencia & Saude Coletiva].
AB - This interview forms part of a series of dialogues that Salud Colectiva has been
holding with key editors in the field, with the purpose of examining the similar
difficulties confronted by Latin American journals and the diverse ways the
journals have faced these difficulties as a likely starting point for uncovering
contextualized solutions. In this interview, carried out in 2015 in the Instituto
de Salud Colectiva of the Universidad Nacional de Lanus, Maria Cecilia de Souza
Minayo speaks to us about the context in which the journal Ciencia & Saude
Coletiva emerged, the political disputes existing within the collective health
field, and the relevance of debate as a constitutive process of science itself.
Additionally, Minayo analyzes both the importance of funding to the growth of a
journal and the problems and difficulties in obtaining funds, which puts into
evidence the lack of policy regarding scientific publishing in Brazil.
PMID- 28414855
TI - Green listed-a CRISPR screen tool.
AB - Motivation: Genome editing using versions of the bacterial CRISPR/Cas9 system can
be used to probe the function of selected genes in any organism. Green Listed is
a web-based tool that rapidly designs custom CRISPR screens targeting sets of
genes defined by the user. It could thus be used to design screens targeting for
example all genes differentially expressed during a specific stimuli or all genes
related to a specific pathway or function, as well as to generate targeted
secondary screens following a large-scale screen. Availability and
Implementation: The software, including a demo function as well as explanatory
texts and videos, is available through greenlisted.cmm.ki.se . Contact:
fredrik.wermeling@ki.se.
PMID- 28414856
TI - Radiographic and ultrasonographic findings of the spleen and abdominal lymph
nodes in healthy domestic ferrets.
AB - OBJECTIVE: To describe the radiographic and ultrasonographic characteristics of
the spleen and abdominal lymph nodes in clinically healthy ferrets. MATERIALS AND
METHODS: Fifty-five clinically healthy ferrets were prospectively recruited for
this cross-sectional study. Three-view whole body radiographs and abdominal
ultrasonography were performed on awake (23 out of 55) or sedated (32 out of 55)
ferrets. On radiographs splenic and abdominal lymph node visibility was assessed.
Splenic thickness and echogenicity and lymph node length, thickness,
echogenicity, number and presence of cyst-like changes were recorded. RESULTS:
The spleen was radiographically detectable in all ferrets. On ultrasound the
spleen was hyperechoic to the liver (55 out of 55) and mildly hyperechoic (28 out
of 55), isoechoic (15 out of 55) or mildly hypoechoic (12 out of 55) to the renal
cortices. Mean splenic thickness was 11.80 +/-0.34 mm. Lymph nodes were
radiographically discernible in 28 out of 55 ferrets and included caudal
mesenteric and sublumbar nodes. An average of 9 +/-2 lymph nodes (mean+/-
standard deviation; mode 10) were identified in each ferret using ultrasound. A
single large jejunal lymph node was identified in all ferrets and had a mean
thickness of 5.28 +/- 1.66 mm. For other lymph nodes the mean thickness
measurements plus one standard deviation were less than 4.4 mm (95% confidence
interval: <= 3.72 mm). CLINICAL SIGNIFICANCE: The information provided in this
study may act as a baseline for evaluation of the spleen and lymph nodes in
ferrets.
PMID- 28414857
TI - Association of external cephalic version before term with late preterm birth.
AB - INTRODUCTION: While evidence suggests that beginning an external cephalic version
(ECV) before term (340/7 to 366/7 weeks) compared with after term may be
associated with an increase in late preterm birth (340/7 to 366/7 weeks), it
remains unknown what might account for this risk. The objective of the present
study is to further investigate the association between ECV before term and late
preterm birth. MATERIAL AND METHODS: Secondary analysis of data collected from
the international, multicenter Early ECV trials. We evaluated the relation
between ECV exposure and late preterm birth (340/7 to 366/7 weeks), as well as
whether additional risk factors for preterm birth (such as maternal age, height,
body mass index, parity, placental location, and perinatal mortality rate)
moderated this relation. Generalized linear mixed methods were used to account
for center effect and adjust for covariates. RESULT: Among 1765 women with breech
pregnancies and without a prior preterm birth, 749 (42.4%) received at least one
ECV before term. Exposure to an ECV before term was not associated significantly
independently with odds of preterm birth. However, placenta location moderated
the association between early ECV exposure and late preterm birth. The odds of
preterm birth in women who were exposed to an ECV before term and who also had an
anterior placenta were doubled (OR 2.05; 95% CI 1.12-3.71; p = 0.02). CONCLUSION:
In a large cohort of women without known risks for preterm birth, those with an
anterior placenta who undergo an ECV before term constitute a subgroup at
particular risk for late preterm birth.
PMID- 28414858
TI - Keratoacanthoma-Like Growths of Incontinentia Pigmenti Successfully Treated with
Intralesional Methotrexate.
AB - We report the case of a 17-year-old girl with incontinentia pigmenti who
developed multiple large hyperkeratotic tumors within Blaschkoid hyperpigmented
patches on her left leg. Biopsy demonstrated an endoexophytic nodule with
irregular invaginations of keratinizing squamous epithelium and a central keratin
filled crater, consistent with keratoacanthoma-like lesions of incontinentia
pigmenti. The tumors were successfully treated with intralesional methotrexate.
PMID- 28414859
TI - Source-receptor probability of atmospheric long-distance dispersal of viruses to
Israel from the eastern Mediterranean area.
AB - Viruses that affect the health of humans and farm animals can spread over long
distances via atmospheric mechanisms. The phenomenon of atmospheric long-distance
dispersal (LDD) is associated with severe consequences because it may introduce
pathogens into new areas. The introduction of new pathogens to Israel was
attributed to LDD events numerous times. This provided the motivation for this
study which is aimed to identify all the locations in the eastern Mediterranean
that may serve as sources for pathogen incursion into Israel via LDD. This aim
was achieved by calculating source-receptor relationship probability maps. These
maps describe the probability that an infected vector or viral aerosol, once
airborne, will have an atmospheric route that can transport it to a distant
location. The resultant probability maps demonstrate a seasonal tendency in the
probability of specific areas to serve as sources for pathogen LDD into Israel.
Specifically, Cyprus' season is the summer; southern Turkey and the Greek islands
of Crete, Karpathos and Rhodes are associated with spring and summer; lower Egypt
and Jordan may serve as sources all year round, except the summer months. The
method used in this study can easily be implemented to any other geographic
region. The importance of this study is the ability to provide a climatologically
valid and accurate risk assessment tool to support long-term decisions regarding
preparatory actions for future outbreaks long before a specific outbreak occurs.
PMID- 28414860
TI - Persistent visual loss in dengue fever due to outer retinal damage.
PMID- 28414861
TI - Management of necrotising fasciitis secondary to abdominal liposuction using a
combination of surgery, hyperbaric oxygen and negative pressure wound therapy in
a patient with burn scars.
AB - Liposuction is the one of the most frequently performed cosmetic operations and
usually has an easy recovery, with a reportedly low overall complication rate.
Here, we report the case of a 60-year-old woman with type II diabetes mellitus
and a previous burn injury of the abdomen who underwent abdominal liposuction and
subsequently developed necrotising fasciitis. Following radical debridement,
systemic antibiotic administration, negative pressure wound therapy and
hyperbaric oxygen therapy, the wound healed completely. This case demonstrates
the success of the combination treatment and highlights the need for clinicians
to be aware of the risk of serious complications in selected patients.
PMID- 28414862
TI - Editorial Perspective: Longitudinal research in autism - introducing the concept
of 'chronogeneity'.
AB - Autism Spectrum Disorder (ASD or autism) is a heterogeneous neurodevelopmental
disorder. We are now at a critical juncture in autism research where we have the
knowledge base and expertise to begin to think about studies that view
heterogeneity, not as 'statistical noise' that can be 'accounted for' using data
reduction techniques (such as group trajectories), but rather as 'informative
variance' that can help form a more precise and dynamic picture of autism. In
this Editorial we coin a new term and introduce the concept of 'chronogeneity'
for the study of autism heterogeneity in relation to the dimension of time
(chrono). Using examples of ongoing research and analytical advances we build the
case for the potential utility of the concept of 'chronogeneity' and argue that a
refined approach to the longitudinal investigation of autism (and other
neurodevelopmental disorders) may move us closer to more precise and adaptive
models of care for the children and youth affected by these disorders.
PMID- 28414863
TI - Commentary: On the importance of looking at nonlinearity and developmental
effects - a reflection on Flom et al. (2017).
AB - By examining both linear and curvilinear associations between mental development
and activity level, the study by Flom et al. (Journal of Child Psychology and
Psychiatry, 2017) highlights the importance of going beyond linear associations
in psychological fields of research. Results from Flom et al. (Journal of Child
Psychology and Psychiatry, 2017) also raise interesting questions for future
research. First, studies should look at variables that may explain the
associations between activity level and mental development, such as self
regulation and attention. Second, longitudinal changes in the strength of the
association between activity level and mental development should be examined to
determine when this association is at its strongest. Finally, longitudinal
research looking at bidirectional effects is needed to confirm the direction of
the associations between activity level and mental development. Answers to these
questions will allow the identification of the best targets and developmental
periods for interventions to take place.
PMID- 28414864
TI - Editorial: Finding the silver lining: incorporating resilience and adaptiveness
into studies of psychopathology.
AB - The editor muses about studies that might complement and enhance current
etiologic studies of psychopathology, many of which focus on monotonically
increasing maladaptative outcomes in response to increasing levels of
risk/vulnerability. More meaningful and consistent considerations of the
resilience counterfactual (e.g., Why are some youth with a given neural deficit
unaffected? Why are some youth exposed to a given adversity unaffected?) should
strengthen our causal inferences. We might also more frequently test for U-shaped
associations with outcome (e.g., Does level of psychopathology predict
deleterious outcomes in a dose-response fashion, or is the association
curvilinear whereby moderate predict good outcomes?). In line with the latter, we
might also more frequently consider the adaptive value of the disorder in
evolutionary terms (e.g., Why is this disorder still part of the human
repertoire? What might be its adaptive value for the species?).
PMID- 28414865
TI - Transvaginal sonography in the diagnosis of deep infiltrating endometriosis: A
review.
AB - This review summarizes the current evidence regarding the diagnostic accuracy of
sonography (US) in women with deep infiltrating endometriosis (DIE). It is well
known that transvaginal ultrasound (TVUS) can detect ovarian endometriomas with a
high degree of sensitivity. In recent years, US has also been used to detect DIE.
In the hands of an experienced sonologist, the sensitivity and specificity of
TVUS in the detection of DIE is comparable to those of MRI. TVUS can eliminate
the need for an MRI in the majority of patients and reduce the need for
diagnostic laparoscopy, proving to be an important tool in preoperative planning.
(c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:313-318, 2017.
PMID- 28414867
TI - Basic-education mexican teachers' knowledge of biotechnology and attitudes about
the consumption of genetically modified foods.
AB - Over the past few years, a new research field has emerged, focusing on the social
scientific criteria for the study of opinions toward genetically modified foods
(GMFs), since these may be limiting factors for the success or failure of these
products. Basic education is the first step in the Mexican education system, and
teachers may wield an outsized influence on the attitudes and preferences of
children, prospective future consumers of these products. To better understand
the current state of knowledge of biotechnology issues and opinions toward the
consumption of GMF of Mexican teachers, a questionnaire was distributed, and 362
Mexican teachers of basic education responded. The survey included questions
about the benefits and risks of consuming GMF. The mean percentage of teachers
expressing knowledge of a given topic in biotechnology was 50%. More than 60% of
teachers believed that GMFs would be useful in preventing world hunger, while
39.2% considered GMF to be hazards for future generations. Although 47.0%
reported not having enough knowledge about these topics, almost all (90.3%)
respondents expressed an interest and willingness to learn about biotechnology.
In light of the fact that teachers of basic education represent the first and
potentially most lasting stage in the education of young children, this survey
establishes the urgent need to develop strategies to improve the scientific
knowledge of teachers and to facilitate decision making and the promotion of
scientific and technological advances for their students. (c) 2017 by The
International Union of Biochemistry and Molecular Biology, 45(5):396-402, 2017.
PMID- 28414866
TI - Characterizing the outcomes of metastatic papillary renal cell carcinoma.
AB - Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly
characterized in the era of targeted therapy. A total of 5474 patients with
metastatic renal cell carcinoma (mRCC) in the International mRCC Database
Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between
clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type
I and type II papillary patients (n = 30 and n = 165, respectively). Overall
survival (OS), progression-free survival (PFS), and overall response rate (ORR)
favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard
ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were
detected between type I and II PRCC in this limited dataset. The median OS for
type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P =
0.096). The IMDC prognostic model was able to stratify pRCC patients into
favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor
risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even
after controlling for IMDC prognostic factors. The IMDC prognostic model was able
to effectively stratify pRCC patients.
PMID- 28414868
TI - Protective Effects of Diallyl Sulfide Against Ethanol-Induced Injury in Rat
Adipose Tissue and Primary Human Adipocytes.
AB - BACKGROUND: Alcohol consumption is the fourth leading cause of death and
disability worldwide. Several cellular pathways contribute to alcohol-mediated
tissue injury. Adipose tissue apart from functioning as an endocrine organ
secretes several hormones and cytokines known as adipokines that are known to
play a significant role in alcohol-induced tissue damage. This study was designed
to test the efficacy of diallyl sulfide (DAS) in regulating the alcohol-induced
outcomes on adipose tissue. METHODS: Male Wistar rats were fed with 36% Lieber
DeCarli liquid diet containing ethanol (EtOH) for 4 weeks. Control rats were pair
fed with isocaloric diet containing maltodextrin instead of EtOH. During the last
week of feeding protocol, the EtOH-fed rat group was given 200 mg/kg body weight
of DAS through diet. We also studied DAS effect on isolated human primary
adipocytes. Viability of human primary adipocytes on DAS treatment was assessed
by MTT assay. Malondialdehyde (MDA), a marker of oxidative stress, was measured
by HPLC and the thiobarbituric acid method. Expression of inflammatory genes and
lipogenic genes was studied by qRT-PCR and Western blotting. Serum inflammatory
gene expression was studied by ELISA. RESULTS: Our study results showed that DAS
could alleviate EtOH-induced expression levels of proinflammatory and endoplasmic
reticulum (ER) stress genes and improve adipose tissue mass and adipocyte
morphology in male Wistar rats fed Lieber-DeCarli diet containing 6% EtOH.
Further, we showed that DAS reduced the expression of lipogenic genes and
improved lipid accumulation and adipocyte mass in human primary adipocytes
treated with EtOH. Subsequently, we also showed that oxidative stress, as
measured by the changes in MDA levels, was reduced in both male Wistar rats and
human primary adipocytes treated with EtOH plus DAS. CONCLUSIONS: Our study
results prove that DAS is effective in ameliorating EtOH-induced damage to
adipose tissue as evidenced by the reduction brought about by DAS in oxidative
stress, ER stress, and proinflammatory gene expression levels. DAS treatment also
regulated lipogenic gene expression levels, thereby reducing free fatty acid
release. In conclusion, this study has clinical implications with respect to
alcohol-induced adipose tissue injury among alcohol users.
PMID- 28414869
TI - Zygomaticomaxillary suture maturation: A predictor of maxillary protraction? Part
I - A classification method.
AB - OBJECTIVE: The aim of this study was to present a method of classifying the
maturational level of the zygomaticomaxillary sutures (ZMSs). METHODS: Cone-beam
CT (CBCT) images from 74 subjects (5.6-58.4 years) were examined to define the
radiographic stages of ZMS maturation. Five stages of maturation of the ZMS were
identified and defined: Stage A-uniform high-density sutural line, with no or
little interdigitation; Stage B-scalloped appearance of the high-density sutural
line; Stage C-two parallel, scalloped, high-density lines, separated in some
areas by small low-density spaces; Stage D-fusion in the inferior portion of the
suture; and Stage E-complete fusion. Intra- and inter-examiner agreements were
evaluated by weighted kappa tests. RESULTS: The intra- and inter-examiners
reproducibility values demonstrated substantial to almost perfect agreement. No
fusion of ZMSs was observed in patients up to 10 years of age. From 10 to 15
years, all maturational stages were identified. After 15 years of age, the
majority of patients showed fusion of ZMSs. CONCLUSIONS: The classification of
ZMS maturation using CBCT is a reliable method that allows the assessment of the
morphology of the ZMSs in the individual patient.
PMID- 28414871
TI - Effect of platelet-rich plasma on orthodontic tooth movement in dogs.
AB - OBJECTIVES: To evaluate the effect of platelet-rich plasma (PRP) on the rate of
orthodontic tooth movement. METHODS: The sample comprised six skeletally mature
male mongrel dogs. The maxillary second premolar in each dog was extracted
bilaterally. PRP was prepared and injected around the first premolar in one
randomly selected maxillary quadrant while the other quadrant served as the
control. Coil springs (150 g) were used to distalize the first premolars for 63
days using TAD as anchorage. RESULTS: Total maxillary tooth movement was
significantly faster on the experimental than on the control side. CONCLUSION:
Local injection of PRP in the present animal study resulted in accelerated
orthodontic tooth movement with no obvious clinical or microscopic side effects.
PMID- 28414870
TI - Three-dimensional skeletal mandibular changes associated with Herbst appliance
treatment.
AB - OBJECTIVES: Three-dimensional evaluation of skeletal mandibular changes following
Herbst appliance treatment. SETTING AND SAMPLE POPULATION: Retrospective case
control study, based on a sample size calculation. Twenty-five pubertal patients
treated with Herbst appliance (HAG), and 25 matched Class II patients who
received other non-orthopaedic dental treatments (CG). MATERIAL AND METHODS:
Three-dimensional models were generated from pre-treatment (T0) and post
treatment (T1) cone beam computed tomograms. Volumetric registration on the
cranial base was used to assess mandibular displacement; volumetric regional
registration was performed to evaluate mandibular growth. Quantitative
measurements of X, Y, Z and 3D Euclidian changes, and also qualitative
visualization by colour-mapping and semi-transparent overlays were obtained.
RESULTS: Downward displacement of the mandible was observed in both HAG and CG
(2.4 mm and 1.5 mm, respectively). Significant forward displacement of the
mandible was observed in the HAG (1.7 mm). HAG showed greater 3D superior and
posterior condylar growth than the CG (3.5 mm and 2.0 mm, respectively). Greater
posterior growth of the ramus was noted in the HAG than in CG. CONCLUSIONS:
Immediately after Herbst therapy, a significant mandibular forward displacement
was achieved, due to increased bone remodelling of the condyles and rami compared
to a comparison group. Three-dimensional changes in the direction and magnitude
of condylar growth were observed in Herbst patients.
PMID- 28414872
TI - A scoping review of outcomes related to orthodontic treatment measured in cleft
lip and palate.
AB - The aim of this study was to identify and summarize the outcomes measured in
orthodontic studies of children with cleft lip and/or palate. The objectives were
to categorize the outcomes into pre-determined domains and to explore whether any
domains were under-represented. Electronic databases and grey literature were
searched until December 2016 to identify all studies of orthodontic treatment
interventions in children and adolescents with cleft lip and palate. Abstracts
and subsequently eligible full-text articles were screened independently and in
duplicate by two reviewers. All reported outcome measures were identified and
categorized into six predetermined outcome domains. The search identified 833
abstracts. The majority of studies did not assess orthodontic interventions and
were therefore not eligible for inclusion. Consequently, following screening 71
eligible articles were retrieved in full, of which 40 met the inclusion criteria.
Morphological features of malocclusion were measured in 27 studies (68%) and
adverse effects of orthodontic treatment in 10 (25%). Functional status (n=4;
10%), physical consequences of malocclusion (n=3; 7.5%), quality of life (n=3;
7.5%) and health resource utilization (n=2; 5%) were rarely considered.
Relatively few studies concerning patients with cleft lip and palate focused on
orthodontic interventions. Most of the identified outcomes were concerned with
measuring morphological treatment-related changes and do not reflect patient
perspectives.
PMID- 28414873
TI - Influence of pharyngeal airway respiration pressure on Class II mandibular
retrusion in children: A computational fluid dynamics study of inspiration and
expiration.
AB - OBJECTIVES: To examine the influence of negative pressure of the pharyngeal
airway on mandibular retraction during inspiration in children with nasal
obstruction using the computational fluid dynamics (CFD) method. SETTING AND
SAMPLE POPULATION: Sixty-two children were divided into Classes I, II (mandibular
retrusion) and III (mandibular protrusion) malocclusion groups. MATERIAL AND
METHODS: Cone-beam computed tomography data were used to reconstruct three
dimensional shapes of the nasal and pharyngeal airways. Airflow pressure was
simulated using CFD to calculate nasal resistance and pharyngeal airway pressure
during inspiration and expiration. RESULTS: Nasal resistance of the Class II
group was significantly higher than that of the other two groups, and
oropharyngeal airway inspiration pressure in the Class II (-247.64 Pa) group was
larger than that in the Class I (-43.51 Pa) and Class III (-31.81 Pa) groups
(P<.001). The oropharyngeal airway inspiration-expiration pressure difference in
the Class II (-27.38 Pa) group was larger than that in the Class I (-5.17 Pa) and
Class III (0.68 Pa) groups (P=.006). CONCLUSION: Large negative inspiratory
pharyngeal airway pressure due to nasal obstruction in children with Class II
malocclusion may be related to their retrognathia.
PMID- 28414874
TI - In vitro evaluation of the influence of velocity on sliding resistance of
stainless steel arch wires in a self-ligating orthodontic bracket.
AB - INTRODUCTION: Of the variables used by in vitro studies of resistance to sliding
(RS) in orthodontics, sliding velocity (SV) of the wire is often the one farthest
from its clinical counterpart. We investigated whether velocity influences the RS
at values approximating the orthodontic movement. METHODS: A SS self-ligating
bracket with a NiTi clip was fixed onto a custom-made model. Different shaped
orthodontic SS wires of four sizes and two types (round, 0.020" and 0.022";
rectangular, 0.016"*0.022" and 0.017"*0.025") were tested using an Instron(r)
testing machine. Wires were pulled at four velocities (1*10-2 mm/s, 1*10-3
mm/s, 1*10-4 mm/s, 1*10-5 mm/s). Shapiro-Wilk test was used to evaluate the
normal distribution of the data; two-way ANOVA was performed to compare means in
the RS with wire characteristics and SV. Significance level was set at P<.05.
RESULTS: RS was higher for rectangular wires, and for those with larger
diameters. Lower SV was associated with lower RS, with wire type and size having
an interaction effect. The RS relatively to SV can be represented as: RS ?
alpha[ln(SV)]+beta, where alpha and beta are constants. CONCLUSIONS: At very low
SV and low normal forces, SV influences the RS of SS archwires in orthodontic
brackets, and the proportionality is logarithmic. Although respecting these
parameters in vitro is challenging, quantitative evaluations of RS should be
carried out at clinically relevant velocities if aiming at translational
application in the clinical scenario.
PMID- 28414875
TI - Royal Australasian College of Surgeons 86th Annual Scientific Congress, Adelaide,
Australia, 8-12 May 2017.
PMID- 28414876
TI - Are extremely preterm born children with autism the victims of too much isolation
in the incubator?
PMID- 28414877
TI - Accelerated point of muscle deoxygenation during the 20-m shuttle run test.
AB - This study examined whether the point of accelerated deoxygenation of active
muscle occurs during the 20-m shuttle run test (20mSRT) and, if so, whether it is
associated with exercise performance in the test. Twenty-nine male subjects
performed the 20mSRT, and concentration changes in oxyhaemoglobin (DeltaOxy-Hb)
and deoxyhaemoglobin (DeltaDeoxy-Hb) in the m. vastus lateralis were measured
using a portable near-infrared spectroscopy device. The difference between the
relative concentration changes in DeltaOxy-Hb and DeltaDeoxy-Hb (Delta[Oxy-Hb -
Deoxy-Hb]) was regarded as the muscle oxygenation index. Group-averaged Delta[Oxy
Hb - Deoxy-Hb] showed progressive decrease during the test. However, among the
individuals, we found an accelerated point of decrease in Delta[Oxy-Hb - Deoxy
Hb] in 20 subjects, which revealed that the laps at the accelerated point
correlated with the total laps (r = 0.78). These results demonstrate that the
accelerated deoxygenation of active muscle occurs during the 20mSRT, but not in
all cases. Our findings also indicate that if the accelerated point of muscle
deoxygenation occurs, the timing of its appearance is related to 20mSRT
performance.
PMID- 28414878
TI - Do outdoor workers know their risk of NMSC? Perceptions, beliefs and preventive
behaviour among farmers, roofers and gardeners.
AB - BACKGROUND: Non-melanoma skin cancer (NMSC) was officially recognized in 2015 as
an occupational disease for outdoor workers in Germany. Together with the
enormous socioeconomic impact of NMSC, this has led to the continuous demand of
evidence-based prevention. However, studies assessing the perceptions and beliefs
along with risk behaviour of outdoor workers as an essential prerequisite for
prevention are rare. OBJECTIVE: To assess perceptions, beliefs, barriers, risk
and preventive behaviours towards non-melanoma skin cancer among different
outdoor groups as a basis for the development of sustainable prevention
programmes. PATIENTS AND METHODS: Cross-sectional study among outdoor workers of
three different occupational groups (farmer, gardener, roofer) using a 20
question online survey on NMSC awareness, risk and preventive behaviours.
RESULTS: Between March and April 2016, 353 outdoor workers participated in the
study. Of these, 153 (43.4%) reported never to use sunscreen during work. Wearing
headgear and long pants were the most common sun protection measures. Poor use of
sunscreen was more likely in males and farmers. A low perceived skin cancer risk
was significantly associated with poor use of sunscreen, long-sleeved shirts,
sunglasses and headgear. CONCLUSIONS: Despite great evidence on NMSC risk in
outdoor professions throughout the literature, high-risk groups in fact are not
yet aware of the topic. Sustainable target group-oriented awareness prevention
programmes are needed to lower the immense burden of NMSC.
PMID- 28414880
TI - A new class of ribozyme from hepatitis B virus.
AB - In this issue, Chakraborty and Ghosh present initial in vitro data indicating a
53-base part of the hepatitis B virus (HBV) epsilon region is a ribozyme with
unusual properties. Self-cleavage first occurred at the HBV non-canonical
polyadenylation signal UAUAAA and the "centre bulge" of the epsilon region,
releasing a ribozyme. The released ribozyme then acted as a new class of trans
cleaving ribozyme cleaving other RNAs.
PMID- 28414882
TI - The effect of a faith community nurse network and public health collaboration on
hypertension prevention and control.
AB - BACKGROUND: As part of the Association of State and Territorial Health Official's
Million Hearts State Learning Collaborative in 2014 and 2015, Washington County,
Maryland formed a collaboration between the local health department, health
system and faith community nurse network to address the undiagnosed and
uncontrolled hypertension in the county. OBJECTIVES: Data were analyzed to
determine the effect of a faith community nursing intervention of teaching blood
pressure self-monitoring and coaching blood pressure and lifestyle changes in the
at-risk and hypertensive population. METHODS: Thirty-nine faith community nurses
offered a 3-month blood pressure self-monitoring and coaching intervention in
2014 and 2015 to 119 participants. A secondary data analysis using a repeated
measure ANOVA to assess the differences in pre- and post-intervention systolic
and diastolic blood pressure readings and a paired t-test to compare pre- and
post-lifestyle scores was completed. RESULTS: A total of 109 participants
completed the program and were included in the analysis and were showing
decreased blood pressure readings and improved lifestyle satisfaction scores in
six out of seven areas across the program period. CONCLUSION: Coaching by faith
community nurses creates an environment of sustained support that can promote
improved lifestyles and blood pressure changes over time.
PMID- 28414883
TI - Temperature and rainfall interact to control carbon cycling in tropical forests.
AB - Tropical forests dominate global terrestrial carbon (C) exchange, and recent
droughts in the Amazon Basin have contributed to short-term declines in
terrestrial carbon dioxide uptake and storage. However, the effects of longer
term climate variability on tropical forest carbon dynamics are still not well
understood. We synthesised field data from more than 150 tropical forest sites to
explore how climate regulates tropical forest aboveground net primary
productivity (ANPP) and organic matter decomposition, and combined those data
with two existing databases to explore climate - C relationships globally. While
previous analyses have focused on the effects of either temperature or rainfall
on ANPP, our results highlight the importance of interactions between temperature
and rainfall on the C cycle. In cool forests (< 20 degrees C), high rainfall
slowed rates of C cycling, but in warm tropical forests (> 20 degrees C) it
consistently enhanced both ANPP and decomposition. At the global scale, our
analysis showed an increase in ANPP with rainfall in relatively warm sites,
inconsistent with declines in ANPP with rainfall reported previously. Overall,
our results alter our understanding of climate - C cycle relationships, with high
precipitation accelerating rates of C exchange with the atmosphere in the most
productive biome on earth.
PMID- 28414885
TI - Nasopharyngeal tumor developing in a 36-year-old man following radiation for a
childhood meningioma.
PMID- 28414886
TI - 50-year-old man with a falcine mass.
PMID- 28414887
TI - 61-year-old man with chronic expansile sellar mass.
PMID- 28414888
TI - Models of human adamantinomatous craniopharyngioma tissue: Steps toward an
effective adjuvant treatment.
AB - Even though ACP is a benign tumor, treatment is challenging because of the
tumor's eloquent location. Today, with the exception of surgical intervention and
irradiation, further treatment options are limited. However, ongoing molecular
research in this field provides insights into the pathways involved in ACP
pathogenesis and reveal a plethora of druggable targets. In the next step,
appropriate models are essential to identify the most suitable and effective
substances for clinical practice. Primary cell cultures in low passages provide a
proper and rapid tool for initial drug potency testing. The patient-derived
xenograft (PDX) model accommodates ACP complexity in that it shows respect to the
preserved architecture and similar histological appearance to human tumors and
therefore provides the most appropriate means for analyzing pharmacological
efficacy. Nevertheless, further research is needed to understand in more detail
the biological background of ACP pathogenesis, which provides the identification
of the best targets in the hierarchy of signaling cascades. ACP models are also
important for the continuous testing of new targeting drugs, to establish
precision medicine.
PMID- 28414889
TI - Proteomics in pediatric cystic craniopharyngioma.
AB - Adamantinomatous craniopharyngioma (ACP) is still often burdened by a poor
prognosis in children as far as the risk of recurrence and the quality of life
are concerned. Therefore, many efforts are now dedicated to investigate the
molecular characteristics of this tumor aiming at finding new therapeutic
options. ACP is prevalently a cystic lesion so that an increasing number of
researches are focused on the analysis of its cystic content. In the present
article, the main results of the current proteomic analysis (PA) on the ACP fluid
are summarized. Both "bottom-up" and "top-down" approaches have been utilized. In
the bottom-up approach, proteins and peptides are enzymatically or chemically
digested prior to liquid chromatography and mass spectrometry analyses. The
bottom-up approach pointed out several proteins of the inflammation (namely,
alpha2-HS-glycoprotein, alpha1-antichymotrypsin and apolipoproteins) as possibly
involved in the genesis and growth of the cystic component of ACP. The top-down
strategy analyzes proteins and peptides in the intact state, making it
particularly suitable for the identification of peptides and low molecular weight
proteins and for the characterization of their possible isoforms and post
translational modifications. The top-down approach disclosed the presence of the
thymosin beta family. Thymosin beta4, in particular, which is involved in the
cytoskeleton organization and migration of several tumors, could play a role in
the progression of ACP. Finally, PA was utilized to investigate alterations in
cyst fluid character after treatment with interferon-alpha. The analyzed samples
showed a progressive reduction of the levels of alpha-defensins (proteins
involved in the inflammatory-mediated response) after the intracystic injection
of interferon-alpha, thus reinforcing the hypothesis that inflammation
contributes to ACP cyst pathogenesis. Additional studies on the solid component
of ACP are still necessary to further validate the previous results and to
identify possible markers for targeted therapy.
PMID- 28414890
TI - Corrigendum.
PMID- 28414891
TI - Genetically engineered mouse models of craniopharyngioma: an opportunity for
therapy development and understanding of tumor biology.
AB - Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar
region in childhood. Two genetically engineered mouse models have been developed
and are giving valuable insights into ACP biology. These models have identified
novel pathways activated in tumors, revealed an important function of paracrine
signalling and extended conventional theories about the role of organ-specific
stem cells in tumorigenesis. In this review, we summarize these mouse models,
what has been learnt, their limitations and open questions for future research.
We then discussed how these mouse models may be used to test novel therapeutics
against potentially targetable pathways recently identified in human ACP.
PMID- 28414892
TI - A 19-year-old male with a well-demarcated parieto-occipital mass.
PMID- 28414893
TI - Impact of viral hepatitis aetiology on survival outcomes in hepatocellular
carcinoma: A large multicentre cohort study.
AB - While HBV and HCV are risk factors for HCC, uncertainty exists as to whether
these viral infections have prognostic significance in HCC. Thus, we compared the
overall survival of patients with HBV, HCV and nonviral HCC, and evaluated
whether the presence of HBV and HCV predicts patient outcomes. We conducted a
multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals
between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour
characteristics and patient outcomes were obtained from hospital databases,
computer records and the Victorian Death Registry. Survival outcomes were
compared between HBV, HCV and nonviral hepatitis cases and predictors of survival
determined using Cox proportional hazards regression. There were 1436 new HCC
cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV
30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral
HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On
multivariate analysis, independent risk factors for survival included HCC
aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and
serum creatinine and albumin. After adjusting for these and method of detection,
HBV remained an independent predictor of improved overall survival when compared
to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR
0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is
independently associated with improved overall survival compared with HCV and
nonviral-related HCC. Further studies are needed to determine the underlying
factor(s) responsible.
PMID- 28414894
TI - Effects of BEAT Cancer randomized physical activity trial on subjective memory
impairments in breast cancer survivors.
PMID- 28414895
TI - The Impact of CT Perfusion Threshold on Predicted Viable and Nonviable Tissue
Volumes in Acute Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Perfusion imaging is used for patient selection in
clinical practice and trials. Postprocessing and definitions of tissue viability
are nevertheless not standardized. We compared the lesion volumes generated with
two well-recognized perfusion tissue definitions in a single-center phase 2
thrombolysis study. METHODS: We analyzed perfusion imaging data from the
Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study
using two popular tissue viability thresholds (ischemic core definition: (1)
cerebral blood volume < 2.0 mL/100 g-1 or (2) relative cerebral blood flow < 40%
that of the contralesional hemisphere and relative delay time >2 seconds;
penumbra definitions: (1) mean transit time > 145% of contralesional hemisphere
or (2) relative delay time < 2 seconds). We compared volumes of core and
penumbra, mismatch ratio, percentage, and volume of penumbra salvaged at 24
hours. RESULTS: We included 73 (tenecteplase = 36, alteplase = 37) patients who
had analyzable perfusion lesions at baseline. Significant differences were found
in core volumes using the two thresholds (33 +/- 37 mL vs. 26 +/- 32 mL, P <
.001), as was mismatch ratio (2.5 +/- .9 vs. 4.2 +/- 3.7, P < 0.001). The volume
of penumbra salvaged at 24 hours (30 +/- 19 mL vs. 35 +/- 26 mL, P = .043)
differed significantly, although the percentages of penumbra salvaged did not (P
= .2). No difference was found between the two thrombolytic agents in the
percentages of penumbra salvaged using either threshold. CONCLUSION: Two commonly
used tissue definitions generated significantly different lesion volumes and
mismatch ratios. Threshold selection may have significant impact on patient
selection for trials or reperfusion therapies.
PMID- 28414896
TI - NK cells in self-limited HCV infection exhibit a more extensively differentiated,
but not memory-like, repertoire.
AB - Natural killer (NK) cells have long been thought of as a purely innate immune
cell population, but increasing reports have described developmental and
functional qualities of NK cells that are commonly associated with cells of the
adaptive immune system. Of these features, the ability of NK cells to acquire
functional qualities associated with immunological memory and continuous
differentiation resulting in the formation of specific NK cell repertoires has
recently been highlighted in viral infection settings. By making use of a unique
cohort of monitored, at-risk intravenous drug users in this study, we were able
to dissect the phenotypic and functional parameters associated with NK cell
differentiation and NK cell memory in patients 3 years after acute HCV infection
and either the subsequent self-clearance or progression to chronicity. We
observed increased expression of cytolytic mediators and markers CD56bright and
NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection.
Patients with a self-limited infection expressed higher levels of differentiation
associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively
differentiated NK cell phenotype is associated with self-clearance in HCV
patients, while the NK cells of chronic patients exhibited more naive and
effector NK cell phenotypic and functional characteristics. The identification of
these distinct NK cell repertoires may shed light on the role NK cells play in
determining the outcome of acute HCV infections, and the underlying immunological
defects that lead to chronicity.
PMID- 28414897
TI - Rapid drink challenge and multiple rapid swallowing: Reproducibility of
esophageal function assessment.
PMID- 28414898
TI - Does my patient still have reflux when ppi therapy does not work?
AB - Gastroesophageal reflux disease (GERD) is a common condition around the world.
The management of this disease is less than satisfying given complexity of
patient presentation and suboptimal diagnostic testing when employed for those
poorly responsive to acid suppressive therapy. In this mini review, we discuss
some new strategies employed for patients with suspected GERD to better
understand disease pathophysiology. We compare the strategies and outline a
clinically relevant approach in this difficult group of patients.
PMID- 28414899
TI - Comparison of sedation by intranasal dexmedetomidine and oral chloral hydrate for
pediatric ophthalmic examination.
AB - BACKGROUND AND AIM: Pediatric ophthalmic examinations can be conducted under
sedation either by chloral hydrate or by dexmedetomidine. The objective was to
compare the success rates and quality of ophthalmic examination of children
sedated by intranasal dexmedetomidine vs oral chloral hydrate. METHODS: One
hundred and forty-one children aged from 3 to 36 months (5-15 kg) scheduled to
ophthalmic examinations were randomly sedated by either intranasal
dexmedetomidine (2 MUg.kg-1 , n = 71) or oral chloral hydrate (80 mg.kg-1 , n =
70). The primary endpoint was successful sedation to complete the examinations
including slit-lamp photography, tonometry, anterior segment analysis, and
refractive error inspection. The secondary endpoints included quality of eye
position, intraocular pressure, onset time, duration of examination, recovery
time, discharge time, any side effects during examination, and within 48 h after
discharge. RESULTS: Sixty-one children were sedated by dexmedetomidine with a
success rate of 85.9%, which is significantly higher than that by chloral hydrate
(64.3%) [OR 3.39, 95% CI: 1.48-7.76, P = 0.003]. Furthermore, children in the
dexmedetomidine group displayed better eye position in anterior segment analysis
than in chloral hydrate group median difference. All children displayed stable
hemodynamics and none suffered hypoxemia in both groups. Oral chloral hydrate
induced higher percentages of vomiting and altered bowel habit after discharge
than dexmedetomidine. CONCLUSIONS: Intranasal dexmedetomidine provides more
successful sedation and better quality of ophthalmic examinations than oral
chloral hydrate for small children.
PMID- 28414900
TI - Precision Templated Bottom-Up Multiprotein Nanoassembly through Defined Click
Chemistry Linkage to DNA.
AB - We demonstrate an approach that allows attachment of single-stranded DNA (ssDNA)
to a defined residue in a protein of interest (POI) so as to provide optimal and
well-defined multicomponent assemblies. Using an expanded genetic code system,
azido-phenylalanine (azF) was incorporated at defined residue positions in each
POI; copper-free click chemistry was used to attach exactly one ssDNA at
precisely defined residues. By choosing an appropriate residue, ssDNA conjugation
had minimal impact on protein function, even when attached close to active sites.
The protein-ssDNA conjugates were used to (i) assemble double-stranded DNA
systems with optimal communication (energy transfer) between normally separate
groups and (ii) generate multicomponent systems on DNA origami tiles, including
those with enhanced enzyme activity when bound to the tile. Our approach allows
any potential protein to be simply engineered to attach ssDNA or related
biomolecules, creating conjugates for designed and highly precise multiprotein
nanoscale assembly with tailored functionality.
PMID- 28414901
TI - Assembled Suprastructures of Inorganic Chiral Nanocrystals and Hierarchical
Chirality.
AB - Chiral organizations ubiquitously exist in biomaterials via hierarchical assembly
of chiral molecules, but assembly of chiral inorganic nanocrystals (NCs) has been
lacking. Recent development of cinnabar HgS NCs that can possess precisely
engineered chirality originating from both atomic lattice and morphology offers
an emerging class of inorganic building blocks to explore their hierarchical
assembly. Two different forms of suprastructures, collinear chains and
propellers, have been achieved with various chiral HgS NC building blocks via
distinct assembly mechanisms. The chiroptical responses of suprastructures are
further evaluated both experimentally and theoretically, and are found to
uniquely depend on intrinsic chirality of building blocks and their coupling. Our
study therefore opens up a gateway to new assembled inorganic suprastructures
with desired chiroptical response for wide-ranging functionalities and
applications by bottom-up modular approach.
PMID- 28414902
TI - Tuning Chemistry and Topography of Nanoengineered Surfaces to Manipulate Immune
Response for Bone Regeneration Applications.
AB - Osteoimmunomodulation has informed the importance of modulating a favorable
osteoimmune environment for successful materials-mediated bone regeneration.
Nanotopography is regarded as a valuable strategy for developing advanced bone
materials, due to its positive effects on enhancing osteogenic differentiation.
In addition to this direct effect on osteoblastic lineage cells, nanotopography
also plays a vital role in regulating immune responses, which makes it possible
to utilize its immunomodulatory properties to create a favorable osteoimmune
environment. Therefore, the aim of this study was to advance the applications of
nanotopography with respect to its osteoimmunomodulatory properties, aiming to
shed further light on this field. We found that tuning the surface chemistry
(amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm)
significantly modulated the osteoimmune environment, including changes in the
expression of inflammatory cytokines, osteoclastic activities, and osteogenic,
angiogenic, and fibrogenic factors. The generated osteoimmune environment
significantly affected the osteogenic differentiation of bone marrow stromal
cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most
promising outcome. This study demonstrated that the osteoimmunomodulation could
be manipulated via tuning the chemistry and nanotopography, which implied a
valuable strategy to apply a "nanoengineered surface" for the development of
advanced bone biomaterials with favorable osteoimmunomodulatory properties.
PMID- 28414903
TI - Nanopore Logic Operation with DNA to RNA Transcription in a Droplet System.
AB - This paper describes an AND logic operation with amplification and transcription
from DNA to RNA, using T7 RNA polymerase. All four operations, (0 0) to (1 1),
with an enzyme reaction can be performed simultaneously, using four-droplet
devices that are directly connected to a patch-clamp amplifier. The output RNA
molecule is detected using a biological nanopore with single-molecule
translocation. Channel current recordings can be obtained using the enzyme
solution. The integration of DNA logic gates into electrochemical devices is
necessary to obtain output information in a human-recognizable form. Our method
will be useful for rapid and confined DNA computing applications, including the
development of programmable diagnostic devices.
PMID- 28414904
TI - In Silico Prediction of Chemicals Binding to Aromatase with Machine Learning
Methods.
AB - Environmental chemicals may affect endocrine systems through multiple mechanisms,
one of which is via effects on aromatase (also known as CYP19A1), an enzyme
critical for maintaining the normal balance of estrogens and androgens in the
body. Therefore, rapid and efficient identification of aromatase-related
endocrine disrupting chemicals (EDCs) is important for toxicology and environment
risk assessment. In this study, on the basis of the Tox21 10K compound library,
in silico classification models for predicting aromatase binders/nonbinders were
constructed by machine learning methods. To improve the prediction ability of the
models, a combined classifier (CC) strategy that combines different independent
machine learning methods was adopted. Performances of the models were measured by
test and external validation sets containing 1336 and 216 chemicals,
respectively. The best model was obtained with the MACCS (Molecular Access
System) fingerprint and CC method, which exhibited an accuracy of 0.84 for the
test set and 0.91 for the external validation set. Additionally, several
representative substructures for characterizing aromatase binders, such as
ketone, lactone, and nitrogen-containing derivatives, were identified using
information gain and substructure frequency analysis. Our study provided a
systematic assessment of chemicals binding to aromatase. The built models can be
helpful to rapidly identify potential EDCs targeting aromatase.
PMID- 28414905
TI - Application of an Acyl-CoA Ligase from Streptomyces aizunensis for Lactam
Biosynthesis.
AB - epsilon-Caprolactam and delta-valerolactam are important commodity chemicals used
in the manufacture of nylons, with millions of tons produced annually. Biological
production of these highly valued chemicals has been limited due to a lack of
enzymes that cyclize omega-amino fatty acid precursors to corresponding lactams
under ambient conditions. In this study, we demonstrated production of these
chemicals using ORF26, an acyl-CoA ligase involved in the biosynthesis of ECO
02301 in Streptomyces aizunensis. This enzyme has a broad substrate spectrum and
can cyclize 4-aminobutyric acid into gamma-butyrolactam, 5-aminovaleric acid into
delta-valerolactam and 6-aminocaproic acid into epsilon-caprolactam. Recombinant
E. coli expressing ORF26 produced valerolactam and caprolactam when 5
aminovaleric acid and 6-aminocaproic acid were added to the culture medium. Upon
coexpressing ORF26 with a metabolic pathway that produced 5-aminovaleric acid
from lysine, we were able to demonstrate production of delta-valerolactam from
lysine.
PMID- 28414906
TI - Protecting Silicon Film Anodes in Lithium-Ion Batteries Using an Atomically Thin
Graphene Drape.
AB - Silicon (Si) shows promise as an anode material in lithium-ion batteries due to
its very high specific capacity. However, Si is highly brittle, and in an effort
to prevent Si from fracturing, the research community has migrated from the use
of Si films to Si nanoparticle based electrodes. However, such a strategy
significantly reduces volumetric energy density due to the porosity of Si
nanoparticle electrodes. Here we show that contrary to conventional wisdom, Si
films can be stabilized by two strategies: (a) anchoring the Si films to a carbon
nanotube macrofilm (CNM) current collector and (b) draping the films with a
graphene monolayer. After electrochemical cycling, the graphene-coated Si films
on CNM resembled a tough mud-cracked surface in which the graphene capping layer
suppresses delamination and stabilizes the solid electrolyte interface. The
graphene-draped Si films on CNM exhibit long cycle life (>1000 charge/discharge
steps) with an average specific capacity of ~806 mAh g-1. The volumetric capacity
averaged over 1000 cycles of charge/discharge is ~2821 mAh cm-3, which is 2 to 5
times higher than what is reported in the literature for Si nanoparticle based
electrodes. The graphene-draped Si anode could also be successfully cycled
against commercial cathodes in a full-cell configuration.
PMID- 28414907
TI - Cell Isolation and Recovery Using Hollow Glass Microspheres Coated with
Nanolayered Films for Applications in Resource-Limited Settings.
AB - Established cell isolation and purification techniques such as fluorescence
activated cell sorting (FACS), isolation through magnetic micro/nanoparticles,
and recovery via microfluidic devices have limited application as disposable
technologies appropriate for point-of-care use in remote areas where lab
equipment as well as electrical, magnetic, and optical sources are restricted. We
report a simple yet effective method for cell isolation and recovery that
requires neither specialized lab equipment nor any form of power source.
Specifically, self-floating hollow glass microspheres were coated with an
enzymatically degradable nanolayered film and conjugated with antibodies to allow
both fast capture and release of subpopulations of cells from a cell mixture.
Targeted cells were captured by the microspheres and allowed to float to the top
of the hosting liquid, thereby isolating targeted cells. To minimize nonspecific
adhesion of untargeted cells and to enhance the purity of the isolated cell
population, an antifouling polymer brush layer was grafted onto the nanolayered
film. Using the EpCAM-expressing cancer cell line PC-3 in blood as a model
system, we have demonstrated the isolation and recovery of cancer cells without
compromising cell viability or proliferative potential. The whole process takes
less than 1 h. To support the rational extension of this platform technology, we
introduce extensive characterization of the critical design parameters: film
formation and degradation, grafting with a poly(ethylene glycol) (PEG) sheath,
and introducing functional antibodies. Our approach is expected to overcome
practical hurdles and provide viable targeted cells for downstream analyses in
resource-limited settings.
PMID- 28414908
TI - Experimental-Computational Study of Carbon Nanotube Effects on Mitochondrial
Respiration: In Silico Nano-QSPR Machine Learning Models Based on New Raman
Spectra Transform with Markov-Shannon Entropy Invariants.
AB - The study of selective toxicity of carbon nanotubes (CNTs) on mitochondria (CNT
mitotoxicity) is of major interest for future biomedical applications. In the
current work, the mitochondrial oxygen consumption (E3) is measured under three
experimental conditions by exposure to pristine and oxidized CNTs (hydroxylated
and carboxylated). Respiratory functional assays showed that the information on
the CNT Raman spectroscopy could be useful to predict structural parameters of
mitotoxicity induced by CNTs. The in vitro functional assays show that the
mitochondrial oxidative phosphorylation by ATP-synthase (or state V3 of
respiration) was not perturbed in isolated rat-liver mitochondria. For the first
time a star graph (SG) transform of the CNT Raman spectra is proposed in order to
obtain the raw information for a nano-QSPR model. Box-Jenkins and perturbation
theory operators are used for the SG Shannon entropies. A modified RRegrs
methodology is employed to test four regression methods such as multiple linear
regression (LM), partial least squares regression (PLS), neural networks
regression (NN), and random forest (RF). RF provides the best models to predict
the mitochondrial oxygen consumption in the presence of specific CNTs with R2 of
0.998-0.999 and RMSE of 0.0068-0.0133 (training and test subsets). This work is
aimed at demonstrating that the SG transform of Raman spectra is useful to encode
CNT information, similarly to the SG transform of the blood proteome spectra in
cancer or electroencephalograms in epilepsy and also as a prospective
chemoinformatics tool for nanorisk assessment. All data files and R object models
are available at https://dx.doi.org/10.6084/m9.figshare.3472349 .
PMID- 28414909
TI - Examining the Effect of Exchange-Correlation Approximations in First-Principles
Dynamics Simulation of Interfacial Charge Transfer.
AB - We examine the extent to which the exchange-correlation (XC) approximation
influences modeling interfacial charge transfer using fewest-switches surface
hopping (FSSH) simulations within the single-particle description. A
heterogeneous interface between a lithium ion and an extended boron-nitride sheet
was considered here, being an extreme case in which wave function localization
and energy level alignments are highly sensitive to the XC approximation. The
PBE0 hybrid XC approximation yields nonadiabatic couplings (NACs) that are
significantly smaller than the values obtained from the PBE-GGA approximation by
an order of magnitude for localized electronic states. This difference between
the two XC functionals for the calculated NACs was found to derive mainly from
the wave function characteristics rather than from the lattice movement although
first-principles molecular dynamics trajectories, along which NACs are obtained,
differ noticeably between the two XC functionals. Using the NACs and single
particle energy level alignments at different levels of theory, FSSH simulations
were performed to model the electron transfer dynamics at the interface. The
electron transfer time scale was found to vary as much as, but not more than, 1
order of magnitude. The time scale was found to be quite sensitive to both NACs
and energy level alignments. While the order of magnitude consistency for the
charge transfer rate is encouraging even for this rather extreme model of
heterojunction interface, continued advancement in electronic structure methods
is required for quantitatively accurate determination of the transfer rate.
PMID- 28414910
TI - Efficient Criterion To Evaluate Linear Response Theory in Optical Transitions.
AB - The role of the Gaussian statistics on the solvation dynamics upon the photon
excitation of the chromophore is deeply explored. The linear response theory for
the fluorescence Stokes shift is investigated. An analytical formulism is
presented to recast Stokes shift into the contributions of the equilibrium time
correlation functions of the solute-solvent interactions on the excited-state
surface, and the latter is further reformed and depicted by the time relaxation
of the moment. As the first application of the formulism in the molecular
dynamics simulations, it is verified that the efficiency of the linear response
theory relies on the Gaussian characteristics of the dominant moments in terms of
the Stokes shift, which is identified by the same relaxation dynamics between
those moments and the linear order one. The comparisons between the above
observations on the linearity of Stokes shift and the explanations in the
literature are discussed. The key finding is the development of explicit
criterion to measure the appropriateness of applying linear response theory.
PMID- 28414911
TI - A Platform for Analysis of Nanoscale Liquids with an Array of Sensor Devices
Based on Two-Dimensional Material.
AB - Analysis of nanoscale liquids, including wetting and flow phenomena, is a
scientific challenge with far reaching implications for industrial technologies.
We report the conception, development, and application of an integrated platform
for the experimental characterization of liquids at the nanometer scale. The
platform combines the functionalities of a two-dimensional electronic array of
sensor devices with in situ application of highly sensitive optical
microspectroscopy and atomic force microscopy. We demonstrate the performance
capabilities of the platform with an embodiment based on an array of optically
transparent graphene sensors. The application of electronic and optical sensing
in the platform allows for differentiating between liquids electronically, for
determining a liquid's molecular fingerprint, and for monitoring surface wetting
dynamics in real time. In order to explore the platform's sensitivity limits, we
record topographies and optical spectra of individual, spatially isolated sessile
oil emulsion droplets having volumes of less than ten attoliters. The results
demonstrate that integrated measurement functionalities based on two-dimensional
materials have the potential to push lab-on-chip based analysis from the
microscale to the nanoscale.
PMID- 28414912
TI - Observation of Photovoltaic Action from Photoacid-Modified Nafion Due to Light
Driven Ion Transport.
AB - Replacing passive ion-exchange membranes, like Nafion, with membranes that use
light to drive ion transport would allow membranes in photoelectrochemical
technologies to serve in an active role. Toward this, we modified
perfluorosulfonic acid ionomer membranes with organic pyrenol-based photoacid
dyes to sensitize the membranes to visible light and initiate proton transport.
Covalent modification of the membranes was achieved by reacting Nafion sulfonyl
fluoride poly(perfluorosulfonyl fluoride) membranes with the photoacid 8
hydroxypyrene-1,3,6-tris(2-aminoethylsulfonamide). The modified membranes were
strongly colored and maintained a high selectivity for cations over anions.
Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and
ion-exchange measurements together provided strong evidence of covalent bond
formation between the photoacids and the polymer membranes. Visible-light
illumination of the photoacid-modified membranes resulted in a maximum power
producing ionic photoresponse of ~100 MUA/cm2 and ~1 mV under 40 Suns equivalent
excitation with 405 nm light. In comparison, membranes that did not contain
photoacids and instead contained ionically associated RuII-polypyridyl
coordination compound dyes, which are not photoacids, exhibited little-to-no
photoeffects (~1 MUA/cm2). These disparate photocurrents, yet similar yields for
nonradiative excited-state decay from the photoacids and the RuII dyes, suggest
temperature gradients were not likely the cause of the observed photovoltaic
action from photoacid-modified membranes. Moreover, spectral response
measurements supported that light absorption by the covalently bound photoacids
was required in order to observe photoeffects. These results represent the first
demonstration of photovoltaic action from an ion-exchange membrane and offer
promise for supplementing the power demands of electrochemical processes with
renewable sunlight-driven ion transport.
PMID- 28414913
TI - Life-Cycle Assessment Harmonization and Soil Science Ranking Results on Food
Waste Management Methods.
AB - This study reviewed 147 life cycle studies, with 28 found suitable for
harmonizing food waste management methods' climate and energy impacts. A total of
80 scientific soil productivity studies were assessed to rank management method
soil benefits. Harmonized climate impacts per kilogram of food waste range from
0.20 kg of carbon dioxide equivalents (CO2e) for anaerobic digestion (AD) to 0.38
kg of CO2e for landfill gas-to-energy (LFGTE). Aerobic composting (AC) emits
0.10 kg of CO2e. In-sink grinding (ISG) via a food-waste disposer and flushing
for management with other sewage at a wastewater treatment plant emits 0.10 kg of
CO2e. Harmonization reduced climate emissions versus nonharmonized averages.
Harmonized energy impacts range from -0.32 MJ for ISG to 1.14 MJ for AC. AD at
0.27 MJ and LFGTE at 0.40 MJ fall in between. Rankings based on soil studies show
AC first for carbon storage and water conservation, with AD second. AD first for
fertilizer replacement, with AC second, and AC and AD tied for first for plant
yield increase. ISG ranks third and LFGTE fourth on all four soil-quality and
productivity indicators. Suggestions for further research include developing soil
benefits measurement methods and resolving inconsistencies in the results between
life-cycle assessments and soil science studies.
PMID- 28414914
TI - Designing Uniquely Addressable Bio-orthogonal Synthetic Scaffolds for DNA and RNA
Origami.
AB - Nanotechnology and synthetic biology are rapidly converging, with DNA origami
being one of the leading bridging technologies. DNA origami was shown to work
well in a wide array of biotic environments. However, the large majority of
extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus
severely limiting its future applicability as a bio-orthogonal nanotechnology
platform. In this paper we present the design of biologically inert (i.e., "bio
orthogonal") origami scaffolds. The synthetic scaffolds have the additional
advantage of being uniquely addressable (unlike biologically derived ones) and
hence are better optimized for high-yield folding. We demonstrate our fully
synthetic scaffold design with both DNA and RNA origamis and describe a protocol
to produce these bio-orthogonal and uniquely addressable origami scaffolds.
PMID- 28414915
TI - Tethered Fluorogen Assay to Visualize Membrane Apposition in Living Cells.
AB - We describe proof-of-concept for a novel approach for visualizing regions of
close apposition between the surfaces of living cells. A membrane-anchored
protein with high affinity for a chemical ligand is expressed on the surface of
one set of cells, and the cells are co-cultured with a second set of cells that
express a membrane-anchored fluorogen-activating protein (FAP). The co-cultured
cells are incubated with a bivalent reagent composed of fluorogen linked to the
high-affinity ligand, with the concentration of the bivalent reagent chosen to be
less than the binding constant for the FAP-fluorogen pair but greater than the
binding constant for the ligand-high-affinity protein pair. In these conditions,
strong FAP signal is observed only in regions of close proximity between
membranes of the two classes of cell, where high local concentration of fluorogen
favors binding to the FAP.
PMID- 28414916
TI - Quercetin Remodels the Tumor Microenvironment To Improve the Permeation,
Retention, and Antitumor Effects of Nanoparticles.
AB - Our previous work demonstrated that Wnt16 expression in cisplatin-damaged tumor
associated fibroblasts is a key factor contributing to cisplatin resistance in
malignancies. Natural antifibrotic compounds with low toxicities are promising
candidates to downregulate Wnt16 expression, improving the antitumor effect of
cisplatin nanoparticles. Upon screening several natural chemicals, we found that
a dietary flavonoid, quercetin, significantly suppresses Wnt16 expression in
activated fibroblasts. To facilitate drug delivery, we have prepared a targeted
lipid/calcium/phosphate nanoparticle formulation consisting of a prodrug of
quercetin, i.e., quercetin phosphate, with a high loading efficiency (26.6% w/w).
This quercetin nanoparticle with a particle size of around 35 nm significantly
improved the bioavailability and metabolic stability of the parent quercetin.
Quercetin phosphate is released from the nanoparticles and converted back to the
parent quercetin under physiological conditions. Following systemic
administration of quercetin phosphate nanoparticles, a significant downregulation
in Wnt16 expression was observed and further yielded a synergistic antitumor
effect with cisplatin nanoparticles in a stroma-rich bladder carcinoma model. The
alpha-SMA-positive fibroblast and collagen within the tumor decreased
significantly after combination treatment. This suggests that the remodeling of
the tumor microenvironment induced by quercetin plays a critical role in
promoting the synergy. Indeed, our data further confirmed that quercetin
phosphate alone significantly remodeled the tumor microenvironment and increased
the penetration of second-wave nanoparticles into the tumor nests. Collectively,
quercetin phosphate nanoparticles may be a safe and effective way to improve
therapeutic treatment for desmoplastic tumors.
PMID- 28414918
TI - Frogs host faecal bacteria typically associated with humans.
AB - Tree frogs commonly access drinking water tanks; this may have human health
implications. Although amphibians might not be expected to host mammalian faecal
indicator bacteria (FIB), it is possible that they may have human FIB on their
skin after exposure to human waste. We collected faeces and skin wash from green
tree frogs (Litoria caerulea) from a natural environment, a suburban site, and a
suburban site near a creek occasionally contaminated with sewage effluent. We
used molecular techniques to test for FIB that are routinely used to indicate
human faecal contamination. Enterococci colonies were isolated from both faecal
and skin wash samples, and specific markers (Enterococcus faecium and Bacteroides
thetaiotaomicron) were found in frog faeces, demonstrating that these markers are
not human- or mammalian-specific. Bacteroides thetaiotaomicron was detected in
frogs from both natural and urban sites, but E. faecium was only associated with
the sewage impacted site.
PMID- 28414917
TI - Epidemiology of Knee Sprains in Youth, High School, and Collegiate American
Football Players.
AB - CONTEXT: Variations in knee-sprain incidence among competition levels are
unclear but may help inform prevention strategies in American football players.
OBJECTIVE: To describe the epidemiology of knee sprains in youth, high school,
and collegiate football players. DESIGN: Descriptive epidemiology study.
SETTING: Injury and athlete-exposure (AE) data were collected from 3 injury
surveillance programs at the youth, high school, and collegiate competition
levels. PATIENTS OR OTHER PARTICIPANTS: Data from 310 youth, 184 high school,
and 71 collegiate football team-seasons were collected during the 2012 through
2014 seasons. MAIN OUTCOME MEASURE(S): Knee-sprain rates and risks were
calculated for each competition level. Injury rate ratios (IRRs) and risk ratios
(RRs) compared knee-sprain rates by competition level. Injury proportion ratios
(IPRs) compared differences in surgery needs, recurrence, injury mechanism, and
injury activity by competition level. RESULTS: Knee-sprain rates in youth, high
school, and collegiate football were 0.16/1000 AEs, 0.25/1000 AEs, and 0.69/1000
AEs, respectively. Knee-sprain rates increased as the competition level increased
(high school versus youth: IRR = 1.60; 95% confidence interval [CI] = 1.12, 2.30;
collegiate versus high school: IRR = 2.73; 95% CI = 2.38, 3.96). Knee-sprain risk
was highest in collegiate (4.3%), followed by high school (2.0%) and youth (0.5%)
athletes. Knee-sprain risk increased as the competition level increased (high
school versus youth: RR = 3.73; 95% CI = 2.60, 5.34; collegiate versus high
school: RR = 2.14; 95% CI = 1.83, 2.51). Collegiate football had the lowest
proportion of knee sprains that were noncontact injuries (collegiate versus
youth: IPR = 0.54; 95% CI = 0.31, 0.95; collegiate versus high school: IPR =
0.59; 95% CI = 0.44, 0.79) and the lowest proportion that occurred while being
tackled (collegiate versus youth: IPR = 0.44; 95% CI = 0.26, 0.76; collegiate
versus high school: IPR = 0.71; 95% CI = 0.51, 0.98). CONCLUSIONS: Knee-sprain
incidence was highest in collegiate football. However, level-specific variations
in the distributions of knee sprains by injury activity may highlight the need to
develop level-specific policies and prevention strategies that ensure safe sports
play.
PMID- 28414919
TI - Functional characterization of an N-terminally-truncated mitochondrial porin
expressed in Neurospora crassa.
AB - Mitochondrial porin, which forms voltage-dependent anion-selective channels
(VDAC) in the outer membrane, can be folded into a 19-beta-stranded barrel. The N
terminus of the protein is external to the barrel and contains alpha-helical
structure. Targeted modifications of the N-terminal region have been assessed in
artificial membranes, leading to different models for gating in vitro. However,
the in vivo requirements for gating and the N-terminal segment of porin are less
well-understood. Using Neurospora crassa porin as a model, the effects of a
partial deletion of the N-terminal segment were investigated. The protein,
DeltaN2-12porin, is assembled into the outer membrane, albeit at lower levels
than the wild-type protein. The resulting strain displays electron transport
chain deficiencies, concomitant expression of alternative oxidase, and decreased
growth rates. Nonetheless, its mitochondrial genome does not contain any
significant mutations. Most of the genes that are expressed in high levels in
porin-less N. crassa are expressed at levels similar to that of wild type or are
slightly increased in DeltaN2-12porin strains. Thus, although the N-terminal
segment of VDAC is required for complete function in vivo, low levels of a
protein lacking part of the N terminus are able to rescue some of the defects
associated with the absence of porin.
PMID- 28414920
TI - Sharing Data and Materials in Psychological Science.
PMID- 28414921
TI - Distinct distribution patterns of proteobacterial nirK- and nirS-type
denitrifiers in the Yellow River estuary, China.
AB - Denitrification is considered to be the critical process in removing reactive
nitrogen in estuarine ecosystems. In the present study, the abundance, diversity,
and community structure of nirK- and nirS-type denitrifiers were compared in
sediments from the Yellow River estuary. Quantitative polymerase chain reaction
showed that the 2 types of denitrifiers exhibited different distribution patterns
among the samples, indicating their distinct habitat preference. Phylogenetic
analysis revealed that most of the sequences from clusters I, III, IV, and V for
nirK-type denitrifiers were dominant and were distributed at sites where
dissolved oxygen (DO) was lower, and the sequences in the other clusters were
dominant at sites with higher DO. However, there was no spatially heterogeneous
distribution for the nirS-type denitrifier community. Canonical correlation
analysis and correlation analysis demonstrated that the community structure of
nirK was more responsive to environmental factors than was that of nirS.
Inversely, the abundance and alpha-diversity targeting nirS gene could be more
easily influenced by environmental parameters. These findings can extend our
current knowledge about the distribution patterns of denitrifying bacteria and
provide a basic theoretical reference for the dynamics of denitrifying
communities in estuarine ecosystem of China.
PMID- 28414922
TI - Three new active members of the I-OnuI family of homing endonucleases.
AB - In vitro characterization of 3 LAGLIDADG-type homing endonucleases (HEs) (I-CcaI,
I-CcaII, and I-AstI) that belong to the I-OnuI family showed that they are
functional HEs that cleave their respective cognate target sites. These
endonucleases are encoded within group ID introns and appear to be orthologues
that have inserted into 3 different mitochondrial genes: rns, rnl, and cox3. The
endonuclease activity of I-CcaI was tested using various substrates, and its
minimum DNA recognition sequence was estimated to be 26 nt. This set of HEs may
provide some insight into how these types of mobile elements can migrate into new
locations. This study provides additional endonucleases that can be added to the
catalog of currently available HEs that may have various biotechnology
applications.
PMID- 28414923
TI - Determining the True Selectivity Profile of alphav Integrin Ligands Using
Radioligand Binding: Applying an Old Solution to a New Problem.
AB - The arginyl-glycinyl-aspartic acid (RGD) integrin subfamily contains five members
that partner with the alphav subunit: alphavbeta1, alphavbeta3, alphavbeta5,
alphavbeta6, and alphavbeta8. Within the alphav integrins, the epithelially
restricted alphavbeta6 has been identified as playing a key role in the
activation of transforming growth factor beta that is hypothesized to be pivotal
in the development of idiopathic pulmonary fibrosis (IPF). As part of a drug
discovery program to identify a selective alphavbeta6 RGD mimetic for IPF, cell
adhesion and radioligand binding assays were investigated to screen compounds to
determine affinity and alphav integrin selectivity. In this study, a pan-alphav
radioligand was characterized against all the alphav integrins and used to
determine accurate selectivity profiles for literature and novel RGD ligands, as
well as enable an early readout on alphavbeta6 dissociation kinetics. It has been
shown that while cell adhesion offers a high throughput and reliable format for
ranking compounds, there are downsides to this format when comparing selectivity
across alphav integrins. By accurately defining the relationship between these
assay formats, a medicinal chemistry effort has identified novel, high-affinity,
and selective alphavbeta6 RGD mimetics with slow dissociation kinetics, with the
potential to be developed into clinical candidates for IPF.
PMID- 28414924
TI - Vasectomy and Risk of Prostate Cancer: How to Weigh Current Evidence.
PMID- 28414925
TI - Reversion of BRCA1/2 Germline Mutations Detected in Circulating Tumor DNA From
Patients With High-Grade Serous Ovarian Cancer.
AB - Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous
ovarian cancer (HGSC) are associated with favorable responses to chemotherapy.
However, secondary intragenic (reversion) mutations that restore protein function
lead to clinically significant rates of acquired resistance. The goal of this
study was to determine whether reversion mutations could be found in an unbiased
manner in circulating cell-free DNA (cfDNA) to predict treatment response in
HGSC. Patients and Methods Plasma and tumor samples were obtained from 30
patients with HGSC with either BRCA1 or BRCA2 germline mutation. Two cohorts were
ascertained: patients with a malignancy before undergoing primary HGSC debulking
surgery (n = 14) or patients at disease recurrence (n = 16). Paired tumor and
plasma samples were available for most patients (24 of 30). Targeted amplicon,
next-generation sequencing was performed using primers that flanked germline
mutations, whose design did not rely on prior knowledge of reversion sequences.
Results Five patients were identified with intragenic mutations predicted to
restore BRCA1/2 open reading frames, including two patients with multiple
independent reversion alleles. Reversion mutations were only detected in tumor
samples from patients with recurrent disease (five of 16) and only in cfDNA from
patients with a tumor-detected reversion (three of five). Findings from a rapid
autopsy of a patient with multiple independent reversions indicated that
reversion-allele frequency in metastatic sites is an important determinant of
assay sensitivity. Abundance of tumor-derived DNA in total cell-free DNA, as
measured by TP53 mutant allele frequency, also affected assay sensitivity. All
patients with reversions detected in tumor-derived DNA were resistant to platin-
or poly ADP ribose polymerase inhibitor-based chemotherapy. Conclusion Reversion
mutations can be detected in an unbiased analysis of cfDNA, suggesting clinical
utility for predicting chemotherapy response in recurrent HGSC.
PMID- 28414926
TI - Death Within 1 Month of Diagnosis in Childhood Cancer: An Analysis of Risk
Factors and Scope of the Problem.
AB - Purpose Despite advances in childhood cancer care, some patients die soon after
diagnosis. This population is not well described and may be under-reported.
Better understanding of risk factors for early death and scope of the problem
could lead to prevention of these occurrences and thus better survival rates in
childhood cancer. Methods We retrieved data from SEER 13 registries on 36,337
patients age 0 to 19 years diagnosed with cancer between 1992 and 2011. Early
death was defined as death within 1 month of diagnosis. Socioeconomic status data
for each individual's county of residence were derived from Census 2000. Crude
and adjusted odds ratios and corresponding 95% CIs were estimated for the
association between early death and demographic, clinical, and socioeconomic
factors. Results Percentage of early death in the period was 1.5% (n = 555).
Children with acute myeloid leukemia, infant acute lymphoblastic leukemia,
hepatoblastoma, and malignant brain tumors had the highest risk of early death.
On multivariable analysis, an age younger than 1 year was a strong predictor of
early death in all disease groups examined. Black race and Hispanic ethnicity
were both risk factors for early death in multiple disease groups. Residence in
counties with lower than median average income was associated with a higher risk
of early death in hematologic malignancies. Percentages of early death decreased
significantly over time, especially in hematologic malignancies. Conclusion Risk
factors for early death in childhood cancer include an age younger than 1 year,
specific diagnoses, minority race and ethnicity, and disadvantaged socioeconomic
status. The population-based disease-specific percentages of early death were
uniformly higher than those reported in cooperative clinical trials, suggesting
that early death is under-reported in the medical literature. Initiatives to
identify those at risk and develop preventive interventions should be
prioritized.
PMID- 28414927
TI - Integration of free-hand 3D ultrasound and mobile C-arm cone-beam CT: Feasibility
and characterization for real-time guidance of needle insertion.
AB - This work presents development of an integrated ultrasound (US)-cone-beam CT
(CBCT) system for image-guided needle interventions, combining a low-cost
ultrasound system (Interson VC 7.5MHz, Pleasanton, CA) with a mobile C-arm for
fluoroscopy and CBCT via use of a surgical tracker. Imaging performance of the
ultrasound system was characterized in terms of depth-dependent contrast-to-noise
ratio (CNR) and spatial resolution. US-CBCT system was evaluated in phantom
studies simulating three needle-based procedures: drug delivery, tumor ablation,
and lumbar puncture. Low-cost ultrasound provided flexibility but exhibited
modest CNR and spatial resolution that is likely limited to fairly superficial
applications within a ~10cm depth of view. Needle tip localization demonstrated
target registration error 2.1-3.0mm using fiducial-based registration.
PMID- 28414928
TI - New iminodibenzyl derivatives with anti-leishmanial activity.
AB - Leishmaniasis is an infection caused by protozoa of the genus Leishmania and
transmitted by sandflies. Current treatments are expensive and time-consuming,
involving Sb(V)-based compounds, lipossomal amphotericin B and miltefosine.
Recent studies suggest that inhibition of trypanothione reductase (TR) could be a
specific target in the development of new drugs because it is essential and
exclusive to trypanosomatids. This work presents the synthesis and
characterization of new iminodibenzyl derivatives (dado) with ethylenediamine
(ea), ethanolamine (en) and diethylenetriamine (dien) and their copper(II)
complexes. Computational methods indicated that the complexes were highly
lipophilic. Pro-oxidant activity assays by oxidation of the dihydrorhodamine
(DHR) fluorimetric probe showed that [Cu(dado-ea)]2+ has the highest rate of
oxidation, independent of H2O2 concentration. The toxicity to L. amazonensis
promastigotes and RAW 264,7 macrophages was assessed, showing that dado-en was
the most active new compound. Complexation to copper did not have an appreciable
effect on the toxicity of the compounds.
PMID- 28414929
TI - Association of physical injury and mental health: Results from the national
comorbidity survey- adolescent supplement.
AB - Nonfatal injury is common among adolescents in the U.S., but little is known
about the bi-directional associations between injury and mental health. Utilizing
a nationally representative sample of U.S. adolescents, we examined 1)
associations between lifetime mental health history and subsequent injury; 2)
concurrent associations between injury and mental health; and 3) associations
between injury and subsequent mental disorders. Data were drawn from the National
Comorbidity Survey Replication-Adolescent Supplement (NCS-A), a national survey
of adolescents aged 13 through 17 years (N = 10,123). Twelve-month prevalence of
nonfatal injury requiring medical attention was assessed along with lifetime, 12
month, and 30-day prevalence of DSM-IV depressive, anxiety, behavior, substance
use, and bipolar disorders. We used Poisson regression to examine associations
between 1) lifetime history of mental disorders and 12-month exposure to injury;
2) concurrent associations between 12-month exposure to injury and 12-month
prevalence of mental disorders; and 3) 12-month exposure to injury and 30-day
prevalence of mental disorders. A total of 11.6% of adolescents experienced an
injury requiring medical attention in the year before the survey. Lifetime
history of mental disorders was not associated with past-year injury. Behavior
and bipolar disorders were concurrently associated with past-year injury. Past
year injury occurrence predicted increased risk for past-month anxiety disorders
and decreased risk of past-month depressive disorders. Our findings reveal
reciprocal associations between injury and mental disorders and highlight the
need for systematic assessment, prevention, and treatment of mental disorders
among injured youth.
PMID- 28414930
TI - Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role
of heat-shock protein production.
AB - Current antipsychotics reduce positive symptoms and reverse negative symptoms in
conjunction with cognitive behavioral issues with the goal of restoring impaired
occupational and social functioning. However, limited information is available on
their influence on gliogenesis or their neurogenic properties in adult
schizophrenia brains, particularly on GABAergic interneuron production. In the
present study, we used young adult subventricular zone (SVZ)-derived progenitor
cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and
GABAergic interneuron genesis effects of several kinds of antipsychotics on
changes in differentiation function induced by exposure to the NMDA receptor
antagonist MK-801. We herein demonstrated that antipsychotics promoted or
restored changes in the oligodendrocyte/GABAergic interneuron differentiation
functions of NG2(+) cells induced by the exposure to MK-801, which was considered
to be one of the drug-induced schizophrenia model. We also demonstrated that
antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with
differentiation impairment. The antipsychotics olanzapine, aripiprazole, and
blonanserin, but not haloperidol increased HSP90 levels, which were reduced by
the exposure to MK-801. Our results showed that antipsychotics, particularly
those recently synthesized, exerted similar GABAergic interneuron genesis effects
on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing
cellular HSP production, and also suggest that HSP90 may play a crucial role in
the pathophysiology of schizophrenia and is a key target for next drug
development.
PMID- 28414931
TI - Human adipose tissue levels of persistent organic pollutants and metabolic
syndrome components: Combining a cross-sectional with a 10-year longitudinal
study using a multi-pollutant approach.
AB - We aimed to assess the influence of long-term exposure to POPs on the risk of
metabolic syndrome, combining a cross-sectional with a 10-year longitudinal
follow-up design. Residues of eight POPs were quantified in adipose tissue
samples from 387 participants recruited between 2003 and 2004 in Granada province
(Spain). The outcome ("metabolically compromised") was defined as having >=1
diagnosis of type 2 diabetes, hypertension, hypertriglyceridemia, and/or low HDL
cholesterol. The cross-sectional analysis was conducted in the initial cohort,
while the 10-year longitudinal analysis was conducted in those 154 participants
free of any of the so-mentioned metabolic diseases and classified as
"metabolically healthy" at recruitment. Statistical analyses were performed using
single and multi-pollutant approaches through logistic and Cox regression
analyses with elastic net penalty. After adjusting for confounders, beta
hexachlorocyclohexane (beta-HCH) and hexachlorobenzene (HCB) were independently
associated with an increased risk of being metabolically compromised (unpenalized
ORs=1.17, 95% CI=1.01-1.36 and 1.17, 95% CI=0.99-1.38, respectively). Very
similar results were found in the 10-year longitudinal analysis [HRs=1.28, 95%
CI=1.01-1.61 (beta-HCH); 1.26, 95% CI=1.00-1.59 (HCB)] and were in line with
those obtained using elastic net regression. Finally, when the arithmetic sum of
both compounds was used as independent variable, risk estimates increased to
OR=1.25, 95% CI=1.03-1.52 and HR=1.32, 95% CI=1.02-1.70. Our results suggest that
historical exposure to HCB and beta-HCH is consistently associated with the risk
of metabolic disorders, and that these POPs might be partly responsible for the
morbidity risk traditionally attributed to age and obesity.
PMID- 28414932
TI - Trans-popliteal reflux in limbs with and without deep-vein thrombosis of the same
subject: Cross-sectional study.
PMID- 28414933
TI - Clinically relevant bleeding and thrombotic events in non-cirrhotic splanchnic
vein thrombosis. Long-term follow up.
PMID- 28414934
TI - Blood clot parameters: Thromboelastography and scanning electron microscopy in
research and clinical practice.
AB - BACKGROUND: Clotting parameters are informative of overall haematological
healthiness of an individual. Particularly, clotting parameters can be used as a
measure of the degree of pathology of the coagulation system. Thromboelastography
(TEG) is a well-known technique that is an important point-of-care method, as
well as research method. Scanning electron microscopy (SEM) is a novel research
method, but with possible clinical application. However, there are no clear
standardized guidelines for TEG and SEM result interpretation. MATERIALS AND
METHODS: We have an extensive database of results from TEG of hypercoagulable,
hypocoagulable and healthy whole blood (WB) and platelet poor plasma (PPP). These
results were generated using citrated PPP or WB, followed by the addition of
CaCl2, to initiate clot formation. We also have an extensive and comprehensive
database of thousands of clot micrographs, prepared for SEM. We reanalysed all
our data to compile a user-friendly guideline for TEG and SEM. We also discuss
the effects of different storage times on both WB and PPP. RESULTS: We provide a
quick and informative guide that discusses each TEG parameter, in both WB and
PPP. Increases or decreases in the various parameters are indicative of either
hyper- or hypocoagulability. We also show how hypo- and hypercoagulable clots
look like, compared with healthy clots, using SEM analysis of clots created by
adding thrombin to PPP. CONCLUSION: For optimal and speedy interpretation of a
patient's coagulation status, it is essential for the clinician to make an
informed and precise decision regarding clotting propensity. We believe this
guideline will add to the standardization of TEG parameters, and ultimately
contribute to the treatment of patients. These guidelines will also allow
researchers to standardize their data interpretations and ultimately allow for
the use of a global and inclusive database that might be included in precision
medicine approaches.
PMID- 28414935
TI - cDNA cloning, molecular modeling and docking calculations of L-type lectins from
Swartzia simplex var. grandiflora (Leguminosae, Papilionoideae), a member of the
tribe Swartzieae.
AB - The genus Swartzia is a member of the tribe Swartzieae, whose genera constitute
the living descendants of one of the early branches of the papilionoid legumes.
Legume lectins comprise one of the main families of structurally and
evolutionarily related carbohydrate-binding proteins of plant origin. However,
these proteins have been poorly investigated in Swartzia and to date, only the
lectin from S. laevicarpa seeds (SLL) has been purified. Moreover, no sequence
information is known from lectins of any member of the tribe Swartzieae. In the
present study, partial cDNA sequences encoding L-type lectins were obtained from
developing seeds of S. simplex var. grandiflora. The amino acid sequences of the
S. simplex grandiflora lectins (SSGLs) were only averagely related to the known
primary structures of legume lectins, with sequence identities not greater than
50-52%. The SSGL sequences were more related to amino acid sequences of
papilionoid lectins from members of the tribes Sophoreae and Dalbergieae and from
the Cladratis and Vataireoid clades, which constitute with other taxa, the first
branching lineages of the subfamily Papilionoideae. The three-dimensional
structures of 2 representative SSGLs (SSGL-A and SSGL-E) were predicted by
homology modeling using templates that exhibit the characteristic beta-sandwich
fold of the L-type lectins. Molecular docking calculations predicted that SSGL-A
is able to interact with D-galactose, N-acetyl-D-galactosamine and alpha-lactose,
whereas SSGL-E is probably a non-functional lectin due to 2 mutations in the
carbohydrate-binding site. Using molecular dynamics simulations followed by
density functional theory calculations, the binding free energies of the
interaction of SSGL-A with GalNAc and alpha-lactose were estimated as -31.7 and
47.5 kcal/mol, respectively. These findings gave insights about the carbohydrate
binding specificity of SLL, which binds to immobilized lactose but is not
retained in a matrix containing D-GalNAc as ligand.
PMID- 28414936
TI - East Urals Radioactive Trace: Dose-dependent functional-metabolic effects in the
myocardium of the pygmy wood mouse (Apodemus uralensis) taking into account
population size.
AB - The population dynamics, radiometric data and biochemical parameters
(concentrations of total lipids, proteins, DNA and RNA, activity of succinate
dehydrogenase, glucose phosphate isomerase and catalase, as well as lipid
peroxidation level) in the myocardium of the pygmy wood mouse (Apodemus uralensis
Pall., 1811) inhabiting the area of the East Urals Radioactive Trace (EURT) were
analyzed. The functional-metabolic radiation effects as a result external and
internal exposure to 137Cs and 90Sr (unweighted total dose rate 0.04-0.5 mGy/day)
are characterized by a reduction in lipid catabolism, mitochondrial oxidation and
antioxidant defense, as well as the activation of anaerobic glycolysis as well as
the protein-synthesizing and genetic apparatus. The data indicate the low
efficiency of cell energy production and allow us to state that compensatory
myocardial hypertrophy can improve myocardial contractile function. The level of
the functional-metabolic response in pygmy wood mice in the EURT area increased
with increasing whole-body radiation dose rate and was more pronounced with a
large pygmy wood mouse population size. The harmful effects (cardiac
decompensation stage) of synergies resulting from non-radiation and radiation
factors manifest after population abundance above 30 ind./100 trap-day and a
radiation burden above 0.1 mGy/day.
PMID- 28414937
TI - Accessibility of tertiary hospitals in Finland: A comparison of administrative
and normative catchment areas.
AB - The determination of an appropriate catchment area for a hospital providing
highly specialized (i.e. tertiary) health care is typically a trade-off between
ensuring adequate client volumes and maintaining reasonable accessibility for all
potential clients. This may pose considerable challenges, especially in sparsely
inhabited regions. In Finland, tertiary health care is concentrated in five
university hospitals, which provide services in their dedicated catchment areas.
This study utilizes Geographic Information Systems (GIS), together with grid
based population data and travel-time estimates, to assess the spatial
accessibility of these hospitals. The current geographical configuration of the
hospitals is compared to a normative assignment, with and without capacity
constraints. The aim is to define optimal catchment areas for tertiary hospitals
so that their spatial accessibility is as equal as possible. The results indicate
that relatively modest improvements can be achieved in accessibility by using
normative assignment to determine catchment areas.
PMID- 28414938
TI - Violence against children perpetrated by peers: A cross-sectional school-based
survey in Uganda.
AB - Violence against children by peers is a global public health problem. We aimed to
assess factors associated with peer violence victimization among primary school
children in Uganda. We conducted multilevel multivariable logistic regression
analyses of cross-sectional data from 3706 primary students in 42 Ugandan primary
schools. Among primary school students, 29% and 34% had ever experienced physical
and emotional violence perpetrated by their peers, respectively. Factors strongly
associated with both physical and emotional violence were similar and
overlapping, and included exposure to interparental violence, having an attitude
supportive of violence against children from school staff, not living with
biological parents, working for payment, and higher SDQ score. However, we found
that younger age, sharing sleeping area with an adult and achieving a higher
educational performance score, were specifically associated with physical
violence. On the other hand, being female, walking to school, reporting
disability and eating one meal on the previous day, were particularly associated
with emotional violence. Interventions to reduce peer violence should focus on
family contexts, school environments and those with poor socio-economic status
may need extra support.
PMID- 28414939
TI - Reporting rates of child sexual abuse in Indigenous communities in two Australian
jurisdictions.
AB - Child sexual abuse is a significant problem in many Indigenous communities; there
is also evidence of chronic under-reporting of this crime. This study aimed to
compare reporting rates between Indigenous and non-Indigenous cases of child
sexual abuse across two Australian jurisdictions. Datasets comprising child
sexual abuse reports from the Police Information Management Systems of the two
jurisdictions were used to calculate reporting rates, and to compare case
characteristics and case progression. Results indicated that the reporting rate
for child sexual abuse of Indigenous children was between two and four times that
of non-Indigenous children. In the Indigenous cases, the second jurisdiction had
lower reporting rates than the first jurisdiction. Further analysis of the
Indigenous cases only found that cases in the second jurisdiction were more
severe, more likely to have a forensic interview, and more likely for the suspect
to be charged, than in the first jurisdiction. However, there were no significant
differences in conviction rates between the two jurisdictions. Differences
observed in severity and case progression suggest that the lower reporting rates
observed in the second jurisdiction may be due to comparatively high levels of
under-reporting, rather than lower actual levels of child sexual abuse. In
conclusion, reporting rates of child sexual abuse can be better understood when
further information, such as case characteristics and case progression rates, is
available.
PMID- 28414940
TI - Sexual reoffense trajectories with youths in the child welfare system.
AB - The present study sought to determine whether the persistence of problematic
sexualized behaviors (PSBs) committed by boys in the Massachusetts child welfare
system would lend support to previous taxonomies categorizing offenders as early
onset/life course-persistent, adolescence-onset/adolescence-limited, or childhood
limited in their offending behavior. We examined the persistence of PSBs in a
male sample (N=638; age range: two to 17), using a retrospective longitudinal
archival design. Procedures involved a comprehensive archival review of records
from the Department of Children and Families. Subsamples were established by
trifurcating the sample based on age at the time of the boys' first documented
PSB, resulting in age cohorts reflecting early childhood (age two to seven),
middle childhood (age eight to 11), and preadolescence/adolescence (age 12-17).
Results supported the hypothesis that youths who first exhibited PSBs in early
childhood would produce higher sexual reoffense rates during each of three follow
up windows (i.e., three years, five years, and seven years) than youths who first
exhibited such behaviors in middle childhood, or preadolescence/adolescence
(p<0.01 for all group contrasts). Findings supported the distinctions of several
taxonomies classifying youthful offenders in the juvenile justice system. Abuse
reactivity, coping ability, and vulnerability to iatrogenic intervention effects
are considered as some of many possible contributing factors.
PMID- 28414941
TI - Endo-symbiont mediated synthesis of gold nanobactericides and their activity
against human pathogenic bacteria.
AB - Synthesis of gold nanobactericides (AuNBs) were achieved by treating 1mM
chloroaurate with cell free supernatant of Aneurinibacillus migulanus. Formation
of AuNBs was initially was monitored with change in colour to ruby red. Further
confirmation was assessed with UV-visible spectra with maximum absorption
occurring at 510nm. Transmission electron microscopy (TEM) analysis revealed the
polydispersity of AuNBs with size distribution ranging from 10 to 60nm with an
average size of 30nm. Crystalline nature was studied using X-ray diffraction
which exhibited characteristic peaks indexed to Bragg's reflection at 2theta
angle which confers (111), (200), (220), and (311) planes suggesting AuNBs were
face-centred cubic. Fourier transform infrared spectroscopy (FTIR) analysis
revealed absorption peaks occurring at 3341cm-1, 1635cm-1 and 670cm-1 which
corresponds to functional groups attributing to synthesis. The antibacterial
efficacy of AuNBs was tested against selective human pathogenic bacteria and
activity was measured as zone of inhibition by using disc and well diffusion.
Bactericidal activity was interpreted with standard antibiotics gentamicin and
kanamycin. Micro broth dilution assay expressed the minimal concentration of
AuNBs to inhibit the growth of test pathogens. Highest activity was observed
against Pseudomonas aeruginosa (MTCC 7903) with 21.00+/-0.57mm compared to other
pathogens. The possible mode of action of AuNBs on DNA was carried out with in
vitro assay as preliminary test against pathogenic DNA isolated from P.
aeruginosa. Further studies will be interesting enough to reveal the exact
interactive mechanism of AuNBs with DNA. Overall study contributes towards
biogenic synthesis of AuNBs as one of the alternative in combating drug resistant
pathogens.
PMID- 28414942
TI - Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae
(Danio rerio).
AB - 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme of
the mevalonic acid pathway and is required for cholesterol biosynthesis and the
synthesis of Coenzyme Q10 (CoQ10). Statins inhibit HMGCR, thus inhibiting the
downstream products of this pathway including the biosynthesis of decaprenyl
pyrophosphate that is critical for the synthesis of Coenzyme Q10 (CoQ10). We show
that zebrafish (Danio rerio) larvae treated in tank water with Atorvastatin (ATV;
Lipitor) exhibited movement alterations and reduced whole body tissue metabolism.
The ATV-inhibition of HMGCR function altered transcript abundance of muscle
atrophy markers (atrogen-1, murf) and the mitochondrial biogenesis marker (pgc
1alpha). Furthermore, ATV-induced reduction in larval response to tactile stimuli
was reversed with treatment of CoQ10. Together, the implication of our results
contributes to the understanding of the mechanisms of action of the statin
induced damage in this model fish species.
PMID- 28414943
TI - Ship-in-a-bottle CMPO in MIL-101(Cr) for selective uranium recovery from aqueous
streams through adsorption.
AB - Mesoporous MIL-101(Cr) is used as host for a ship-in-a-bottle type adsorbent for
selective U(VI) recovery from aqueous environments. The acid-resistant cage-type
MOF is built in-situ around N,N-Diisobutyl-2-(octylphenylphosphoryl)acetamide
(CMPO), a sterically demanding ligand with high U(VI) affinity. This one-step
procedure yields an adsorbent which is an ideal compromise between homogeneous
and heterogeneous systems, where the ligand can act freely within the pores of
MIL-101, without leaching, while the adsorbent is easy separable and reusable.
The adsorbent was characterized by XRD, FTIR spectroscopy, nitrogen adsorption,
XRF, ADF-STEM and EDX, to confirm and quantify the successful encapsulation of
the CMPO in MIL-101, and the preservation of the host. Adsorption experiments
with a central focus on U(VI) recovery were performed. Very high selectivity for
U(VI) was observed, while competitive metal adsorption (rare earths, transition
metals...) was almost negligible. The adsorption capacity was calculated at
5.32mg U/g (pH 3) and 27.99mg U/g (pH 4), by fitting equilibrium data to the
Langmuir model. Adsorption kinetics correlated to the pseudo-second-order model,
where more than 95% of maximum uptake is achieved within 375min. The adsorbed
U(VI) is easily recovered by desorption in 0.1M HNO3. Three adsorption/desorption
cycles were performed.
PMID- 28414944
TI - Direct and indirect electrochemical reduction prior to a biological treatment for
dimetridazole removal.
AB - Two different electrochemical reduction processes for the removal of
dimetridazole, a nitroimidazole-based antibiotic, were examined in this work. A
direct electrochemical reduction was first carried out in a home-made flow cell
in acidic medium at potentials chosen to minimize the formation of amino
derivatives and then the formation of azo dimer. Analysis of the electrolyzed
solution showed a total degradation of dimetridazole and the BOD5/COD ratio
increased from 0.13 to 0.24. An indirect electrochemical reduction in the
presence of titanocene dichloride ((C5H5)2TiCl2), which is used to reduce
selectively nitro compounds, was then investigated to favour the formation of
amino compounds over hydroxylamines and then to prevent the formation of azo and
azoxy dimers. UPLC-MS/MS analyses showed a higher selectivity towards the
formation of the amino compound for indirect electrolyses performed at pH 2. To
confirm the effectiveness of the electrochemical reduction, a biological
treatment involving activated sludge was then carried out after direct and
indirect electrolyses at different pH. The enhancement of the biodegradability
was clearly shown since mineralization yields of all electrolyzed solutions
increased significantly.
PMID- 28414945
TI - Evaluation of the chelating performance of biopolyelectrolyte green complexes
(NIBPEGCs) for wastewater treatment from the metal finishing industry.
AB - In this paper nonstoichiometric interbiopolyelectrolyte green complexes
(NIBPEGCs) were prepared using chitosan (Ch), alginate (AG) and poly(acrylic
acid)(PAA). They are proposed as innovative formulations (polyelectrolytes and
chelating agents) suitable for the elimination heavy metals contained in
wastewater. This application may represent an integral solution for industries
rejecting solid and aqueous metallic materials; however, it has not been
previously reported. NIBPEGCs physicochemical performance was evaluated based on
pH, particle size, surface charge, isoelectric point, dose, coagulation
flocculation kinetics and chemical affinity with seven metal ions. The
experimental results showed that NIBPEGCs composed by AG/Ch and PAA/Chitosan have
all the three complementary functions: chemical affinity, electrostatic
interaction and particle entrapment anticipating more simple operation units to
remove heavy metals. Complexes of AG/Ch (negative) were higher performance in
removing heavy metals, with a dose window (150-180mg/L), lower dose of 410mg/L
PAA/Ch (negative). Investigation of chelating performances of NIBPEGCs show that
the efficiency of metal removal is: Ca?Cr?Cu?Pb?Ni?Zn?Cd. Transmittance vs time
profiles, metals and zeta potential analysis showed that chelation capacity is
the crucial factor to ensure metallic species removal, followed by physical
entrapment of the metallic colloids. Integrating all presented results allow to
sustain the development of excellent metals removal formulations.
PMID- 28414946
TI - Green synthesis of hybrid graphene oxide/microcrystalline cellulose aerogels and
their use as superabsorbents.
AB - In this work, we developed a green synthesis method to prepare the hybrid
aerogels containing graphene oxide (GO) and microcrystalline cellulose (MCC)
using lithium bromide (LiBr) aqueous solution as the solvent, which insured the
complete dissolution of MCC. The interaction between GO and MCC was investigated
through different methods The results demonstrate that there is a strong
interaction between GO and MCC molecules, which promotes the exfoliation of GO in
the hybrid aerogels. The hybrid GO/MCC aerogels exhibit typical three dimensional
porous structure and the pore morphology can be well adjusted by changing the
content of GO. The adsorption ability of the hybrid aerogels was measured using
methylene blue (MB) as an adsorbate. The results show that the adsorption ability
of GO per unit mass is greatly enhanced compared with the pure GO aerogel,
especially at relatively low GO content the adsorption amount of GO per unit mass
is enhanced up to 2630mg/g. Further results demonstrate that the hybrid GO/MCC
aerogels still obey the pseudo-second-order adsorption model, which is similar to
that of the pure GO aerogel. The mechanism for the amplified adsorption ability
of GO in the hybrid GO/MCC aerogels is then analyzed.
PMID- 28414947
TI - Application of pyrolysis to recycling organics from waste tantalum capacitors.
AB - Tantalum capacitors (TCs) are widely used in electronic appliances. The rapid
replacement of electronic products results in generating large amounts of waste
TCs (WTCs). WTCs, rich in valuable tantalum, are considered as high quality
tantalum resources for recycling. However, environmental pollution will be caused
if the organics of WTCs were not properly disposed. Therefore, effectively
recycling the organics of WTCs is significant for recovering the valuable parts.
This study proposed an argon (Ar) pyrolysis process to recycle the organics from
WTCs. The organic decomposition kinetic was first analyzed by thermogravimetry.
The results showed that the organics were decomposed in two major steps and the
average activation energy was calculated to 234kJ/mol. Then, the suitable
pyrolysis parameters were determined as 550 degrees C, 30min and 100ml/min. The
organics were effectively decomposed and converted to oils (mainly contained
phenol homologs and benzene homologs) and gases (some hydrocarbon). These
pyrolysis products could be reutilized as energy sources. Moreover, based on the
products and bond energy theory, the pyrolysis mechanisms of the organics were
also discussed. Finally, a reasonable technological process for products
utilization was presented. This study contributes to the efficient recycling the
organics before valuable material recovery from WTCs.
PMID- 28414948
TI - Prognostic Factors for Niche Development in the Uterine Caesarean Section Scar.
AB - In a prospective study on 134 women after their first cesarean section prognostic
factors for developing an uterine niche (scar defect) measured with
sonohysterography were evaluated. With multivariable logistic regression anlaysis
the following prognostic factors were identified; enlarged cervical dilatation
and induction of labour. Contractions before labour reduced the risk for niche
development. The predictive value of the model made with this prognostic factors
was low. The development of a niche is a multifactorial proces and more studies
are needed.
PMID- 28414949
TI - EBV-encoded microRNAs profile evaluation in pediatric liver transplant
recipients.
AB - BACKGROUND: Epstein-Barr virus (EBV) infects 90% of the world population,
commonly causing self-limiting infectious mononucleosis or rarely inciting a
range of malignancies. EBV microRNAs (miRNAs) were discovered by sequencing
libraries of small RNAs generated from several EBV-positive cell lines. Little is
known about their roles, but their high stability and easy quantification make
these molecules potential biomarkers. OBJECTIVES: In this study a stem-loop MGB
real-time RT-PCR has been used to detect and quantify miR-BART2-5p, miR-BART15
and miR-BART22 EBV miRNAs levels. STUDY DESIGNS: The profiles of EBV miRNAs
levels were evaluated in 51 serum samples of 37 pediatric liver transplant
patients subdivided in 3 study groups: EBV seronegative, EBV seropositive and PCR
negative, EBV seropositive and PCR positive. RESULTS: miR-BART22 serum levels in
patients with positive EBV PCR were significantly higher than those in patients
with negative EBV PCR (p=0.0005). On the contrary, miR-BART2-5p and miR-BART15
did not exhibit significant difference in positive and negative EBV PCR patients
(p=0.5511 and p=0.3523, respectively). CONCLUSION: This study described a method
for quantitative detection of miR-BART 22, miR-BART2-5p and miR-BART15 EBV miRNAs
in liver transplanted patients, and suggests the use of miR-BART22 as a potential
biomarker for EBV reactivation.
PMID- 28414951
TI - Development of a two-photon fluorescent turn-on probe with far-red emission for
thiophenols and its bioimaging application in living tissues.
AB - Thiophenol is a highly toxic compound which is essential in the field of organic
synthesis and drug design. However, the accumulation of thiophenols in the
environment may cause serious health problems for human bodies ultimately.
Therefore, it is critical to develop efficient methods for visualization of
thiophenol species in biological samples. In this work, an innovative two-photon
fluorescent turn-on probe FR-TP with far-red emission for thiophenols based on FR
NH2 fluorophore and 2,4-dinitrophenylsulfonyl recognition site was reported. The
new probe can be used for thiophenol detection with large far-red fluorescence
enhancement (about 155-fold), rapid response (completed within 100s), excellent
sensitivity (DL 0.363MUM), high selectivity, and lower cellular auto-fluorescence
interference. Importantly, the probe FR-TP can be successfully employed to
visualize thiophenols not only in the living HeLa cells but also in living liver
tissues. In addition, through two-photon tissue imaging, the probe was used to
monitor and investigate biological thiophenol poisoning in the animal model of
thiophenol inhalation for the first time.
PMID- 28414950
TI - A nanobiosensor composed of Exfoliated Graphene Oxide and Gold Nano-Urchins, for
detection of GMO products.
AB - Genetically Modified Organisms, have been entered our food chain and detection of
these organisms in market products are still the main challenge for scientists.
Among several developed detection/quantification methods for detection of these
organisms, the electrochemical nanobiosensors are the most attended which are
combining the advantages of using nanomaterials, electrochemical methods and
biosensors. In this research, a novel and sensitive electrochemical nanobiosensor
for detection/quantification of these organisms have been developed using
nanomaterials; Exfoliated Graphene Oxide and Gold Nano-Urchins for modification
of the screen-printed carbon electrode, and also applying a specific DNA probe as
well as hematoxylin for electrochemical indicator. Application time period and
concentration of the components have been optimized and also several reliable
methods have been used to assess the correct assembling of the nanobiosensor e.g.
field emission scanning electron microscope, cyclic voltammetry and
electrochemical impedance spectroscopy. The results shown the linear range of the
sensor was 40.0-1100.0 femtomolar and the limit of detection calculated as 13.0
femtomolar. Besides, the biosensor had good selectivity towards the target DNA
over the non-specific sequences and also it was cost and time-effective and
possess ability to be used in real sample environment of extracted DNA of
Genetically Modified Organism products. Therefore, the superiority of the
aforementioned specification to the other previously published methods was proved
adequate.
PMID- 28414952
TI - Class 1 integrons as invasive species.
AB - Clinical class 1 integrons are a major contributor to the evolution and
dissemination of antibiotic resistance. The conserved motifs of these integrons
suggest that a single, recent ancestor gave rise to all current variants. They
have had a spectacular increase in distribution and abundance over the last 100
years, exhibiting many similarities to invasive species that prosper under human
impacts. They have spread into over 70 bacterial species of medical importance,
are commonly resident in the gut of humans and domesticated animals, and have
invaded every continent, including Antarctica. They have done so via linkage with
transposons, metal, disinfectant and antibiotic resistance genes. As a
consequence of their invasive nature they have now become significant pollutants
of natural environments.
PMID- 28414953
TI - Health shocks and their long-lasting impact on health behaviors: Evidence from
the 2009 H1N1 pandemic in Mexico.
AB - Worldwide, the leading causes of death could be avoided with health behaviors
that are low-cost but also difficult to adopt. We show that exogenous health
shocks could facilitate the adoption of these behaviors and provide long-lasting
effects on health outcomes. Specifically, we exploit the spatial and temporal
variation of the 2009 H1N1 influenza pandemic in Mexico and show that areas with
a higher incidence of H1N1 experienced larger reductions in diarrhea-related
cases among young children. These reductions continue even three years after the
shock ended. Health improvements and evidence of information seeking via Google
searches were consistent with changes in hand washing behaviors. Several
robustness checks validate our findings and mechanism.
PMID- 28414954
TI - Combination of microbial oxidation and biogenic schwertmannite immobilization: A
potential remediation for highly arsenic-contaminated soil.
AB - Here, a novel strategy that combines microbial oxidation by As(III)-oxidizing
bacterium and biogenic schwertmannite (Bio-SCH) immobilization was first proposed
and applied for treating the highly arsenic-contaminated soil. Brevibacterium sp.
YZ-1 isolated from a highly As-contaminated soil was used to oxidize As(III) in
contaminated soils. Under optimum culture condition for microbial oxidation,
92.3% of water-soluble As(III) and 84.4% of NaHCO3-extractable As(III) in soils
were removed. Bio-SCH synthesized through the oxidation of ferrous sulfate by
Acidithiobacillus ferrooxidans immobilize As(V) in the contaminated soil
effectively. Consequently, the combination of microbial oxidation and Bio-SCH
immobilization performed better in treating the highly As-contaminated soil with
immobilization efficiencies of 99.3% and 82.6% for water-soluble and NaHCO3
extractable total As, respectively. Thus, the combination can be considered as a
green remediation strategy for developing a novel and valuable solution for As
contaminated soils.
PMID- 28414955
TI - Influence of relaxation modes on membrane fouling in submerged membrane
bioreactor for domestic wastewater treatment.
AB - Relaxation and backwashing have become an integral part of membrane bioreactor
(MBR) operations for fouling control. This study was carried out on real
municipal wastewater to evaluate the influence of different operational
strategies on membrane fouling at equivalent water yield. Four relaxation modes
(MBR10+0, MBR10+1, MBR10+1.5 and MBR10+2) were tested to analyze membrane fouling
behavior. For the optimization of relaxation modes, fouling rate in terms of
trans-membrane pressure, hydraulic resistances and characteristics of fouling
fractions were analyzed. It has been observed that cake layer resistance was
minimum in MBR10+1.5 but pore blockage resistance was increased in all relaxation
modes. Moreover, high instantaneous flux contributed significantly to fouling
rate at the initial stage of MBR operations. Relaxation modes were also efficient
in removing irreversible fouling to some extent. Under all relaxation modes, COD
removal efficiency ranged from 92 to 96.5%. Ammonium and TP removal were on the
lower side due to the short solids and hydraulic retention time.
PMID- 28414956
TI - Geosmin as a source of the earthy-musty smell in fruits, vegetables and water:
Origins, impact on foods and water, and review of the removing techniques.
AB - The earthy-musty smell produced by Streptomyces sp. is assigned to geosmin and is
responsible for the major organoleptic defects found in drinking water, fruits
and vegetables such as grapes, mushrooms, carrots, and beet. Geosmin is also
found in juices and musts before fermentation and its presence has been
associated with partial presence of Botrytis cinerea. It has a variable detection
threshold depending on the matrix and the detection level ranges from 5 to 50
ng/L. On the sensory level, very few individuals are immune to geosmin and
although the intensity of the defect caused by this molecule decreases rapidly in
the nose, a bad taste is very persistent in the mouth. As the origin of geosmin
is fungal, conventional control techniques used for geosmin prevention are
limited to ventilation, improving the integrity of plants and use of storage
temperatures around 1 degrees C in a humidity-controlled environment. However,
it has been demonstrated that only the combination of different prophylactic and
preventive measures provide a relatively sufficient efficacy. Therefore,
prevention of factors favoring the formation of geosmin is still topical. Some
chemical treatments showed relatively good results against Botrytis cinerea.
However, there is a requirement that must be met, namely that only one chemical
per family per year must be used. Moreover, a multi-year alternation of chemical
families is a strong agronomic recommendation. Regarding Penicillium, no active
material is 100% approved and it negative effects plants such as beet and grapes.
Consequently, the importance of finding effective ways to fight against geosmin
formation is still relevant. From analytical point of view, measurement of
geosmin is mainly based on gas chromatography.
PMID- 28414957
TI - Emotion socialization and child conduct problems: A comprehensive review and meta
analysis.
AB - Decades of research have emphasized the role that coercive and ineffective
discipline plays in shaping child and adolescent conduct problems, yet an
emerging body of evidence has suggested that parents' emotion socialization
behaviors (ESBs) (e.g., reactions to emotions, discussion of emotions, and
emotion coaching) may also be implicated. This meta-analysis examined concurrent
and longitudinal associations between parental ESBs and conduct problems, and
tested for moderators of these associations. A systematic search identified 49
studies for which data on concurrent associations between ESBs and conduct
problems were available (n=6270), and 14 studies reporting on prospective
associations (n=1899). Parental ESBs were found to be significantly associated
with concurrent (r=-0.08) and prospective (r =-0.11) conduct problems, in the
order of small effect sizes. Key findings of moderator analyses were that ESBs
were more strongly associated with conduct problems at younger ages and when ESBs
were focused on the socialization of negative rather than positive emotions.
Findings support the integration of ESBs into family-based models of antisocial
behavior, and have the potential to inform the design of parent training
interventions for the prevention and treatment of child conduct problems.
PMID- 28414958
TI - The reappearance of hemiplegic cluster headaches: A case report and review of the
literature.
AB - Cluster headache (CH) is a rare and severe syndrome characterized by the
recurrence of unilateral pain attacks, of short duration (15-180min), and
associated with ipsilateral cranial autonomic symptoms. Although, not formally
included in the International Classification of Headache Disorders, hemiplegic
cluster headache (HCH) is an even more rare subtype of CH in which typical
attacks can be accompanied by visual, sensory, and/or aphasic migrainous auras
that have a variable propensity to evolve in reversible hemi-motor symptoms.
After its first description in 2002, only few cases of HCH have been reported and
many open questions about its prevalence and pathophysiology still need to be
addressed. We describe a case of a 41-year old male that fulfilled the ICHD
criteria for episodic CH who experienced atypical attacks characterized by
concomitant acute onset of sensory aura, aphasia and hemi-motor symptoms. We also
provide a concise review of the available literature and discuss the prevalence
and the possible pathogenesis of CH with hemiplegic features.
PMID- 28414959
TI - The visualization of the surgical field in tubular assisted spine surgery: Is
there a difference between HD-endoscopy and microscopy?
AB - OBJECTIVE: Expert spinal surgeons criticized endoscopic procedures for poor image
quality, in comparison to microscopic visualization. The recent introduction of
high definition (HD) digital cameras has shown good results in spinal endoscopy.
The aim of this study was to assess endoscopic HD image quality in comparison
with microscopic visualization. PATIENTS AND METHODS: All posterior lumbar and
cervical spinal surgeries of this study were performed with the EasyGO-system in
HD resolution. For each comparison, anatomical structures were predefined
intraoperatively. A junior resident was randomly required to enter the operating
theatre and to identify those structures either using HD-endoscopic or
microscopic visualization through the endoscopic working sheath. RESULTS:
Thirteen lumbar and three cervical procedures were performed. Thirty-four
comparisons with a total of 214 predefined anatomical structures were analyzed.
The number of predefined structures ranged from 5 to 9 per surgical field. Out of
214 predefined structures, 124 structures (65.8%) were correctly identified under
endoscopic view and 88 (41.1%) under microscopic view (p=0.001). Subjective
impression of visualization quality were rated 1.25 (very good) for endopscopic
images and 1.6 (very good to good) for microscopic view (p=0.02). CONCLUSIONS:
When using a working trocar and live images, endoscopic HD camera imaging
accounted for significantly more reliable identifications of anatomical
structures compared to the microscopic view. The subjective impression of video
quality is significantly better with HD-optics. The goal of further studies
should be to evalute if these findings results in improved surgical outcome.
PMID- 28414960
TI - Calibration of on-chip cell electroporation by a pseudo-volumetric uptake model.
AB - Most conventional methods for assessing uptake of exogenous molecules and
nanomaterials into cells use the projected two-dimensional (2D) area of uptake
intensity into individual cells. However, since most cells have a three
dimensional (3D) spherical shape, volumetric uptake cannot be quantified
accurately using 2D area analysis. Here, we present a method for calibrating the
electroporative uptake intensity of small molecules by using a novel predictable
spherical volume (PSV) model, which is more accurate and quantitative than
previous methods. As a proof-of-concept, we visualized the electroporative uptake
of propidium iodide (PI) into mammalian cells in a single rectangular
polydimethylsiloxane (PDMS) microfluidic channel, often used for direct
observation of on-chip cell electroporation. Our PSV method yielded more accurate
results than conventional methods and faithfully reflected volumetric changes in
uptake intensity, even those due to microflow. We believe that this approach can
be potentially beneficial for screening the electroporative uptake efficiency of
cell-membrane impermeable nanodrugs, such as functional nanoparticles
incorporated with a small drug capable of slowly diffusing inside cells.
PMID- 28414961
TI - Interaction between bacterial cell membranes and nano-TiO2 revealed by two
dimensional FTIR correlation spectroscopy using bacterial ghost as a model cell
envelope.
AB - The interaction between microorganisms and nanoparticles is a crucial step
towards understanding the subsequent biological effect. In this study, the
interaction between TiO2 nanoparticles and bacterial cell membrane was
investigated by Two-dimensional Correlation Fourier Transformation Infrared
spectroscopy (2D-FTIR-COS) using bacterial ghosts (BGs), which are non-living
bacterial cell envelopes devoid of cytoplasm. The synchronous map of 2D-FTIR-COS
results indicated that the functionalities in proteins of BGs preferentially
interacted with TiO2 nanoparticles; whereas the interaction of TiO2 nanoparticles
with characteristic functionality in polysaccharides (COH) and phospholipids (PO)
were very weak or insensitive. This conclusion was further corroborated by
settling of TiO2 nanoparticles in the presence of pure protein, polysaccharide
and phospholipid represented by bovine serum albumin (BSA), alginate and
phosphatidylethanolamine (PE). Additionally, the asynchronous map of 2D-FTIR-COS
indicated a sequential order of functionalities bonded to TiO2 nanoparticles with
the order of: COO- > aromatic CC stretching > NH, amide II > CO, ketone. These
findings contribute to deeper understanding of the interaction between TiO2
nanoparticles and bacterial cell membrane in aquatic systems.
PMID- 28414962
TI - Advanced anaerobic digestion of municipal sludge using a novel and energy
efficient radio frequency pretreatment system.
AB - Microwave (MW) sludge pretreatment systems are usually limited to a frequency of
2.45 GHz and the heating frequency is constrained by commercially available
hardware. Studies using MW heating at this frequency have reported negative net
energy balance (output energy as methane minus input electrical energy). This
necessitates further research into more efficient thermal pretreatment
technologies. In this research, a novel and highly efficient radio frequency (RF)
pretreatment system at a frequency of 13.56 MHz was designed, implemented, and
tested for the first time. The system was custom-designed based on the dielectric
characteristics of thickened waste activated sludge (TWAS) to achieve a very
efficient and uniform heating system. The effects of three factors including
pretreatment method (RF vs. MW), final temperature (60, 90 and 120 degrees C),
and stationary (holding) time (0, 1 and 2 h) on sludge solubilization and
performance of mesophilic batch anaerobic digestion were evaluated
simultaneously. Energy measurements were also made to compare the efficiency of
the custom-designed RF and conventional MW heating systems. The differences in
sludge disintegration (solubilization) using the RF and MW pretreatment systems
were negligible (P > 0.05). No statistically significant difference was also
observed between the two pretreatment systems in terms of mesophilic biogas
production rate and extent (P > 0.05). The energy efficiency of the RF
pretreatment system was measured between 67.3 and 95.5% for the temperature range
of 25-120 degrees C which was significantly higher than that of the MW system
efficiency which varied from 37 to 43%. Overall, the average input energy of the
RF system was less than half of the energy consumed during the operation of the
MW system to achieve a same target temperature. Considering the results of this
research, the RF heating at a frequency of 13.56 MHz is suggested as an effective
and energy-efficient technique for thermal hydrolysis of TWAS.
PMID- 28414963
TI - Three-dimensional excitation and emission matrix fluorescence (3DEEM) for quick
and pseudo-quantitative determination of protein- and humic-like substances in
full-scale membrane bioreactor (MBR).
AB - The goal of this study is to help filling the research gaps linked to the on-line
application of fluorescence spectroscopy in wastewater treatment and data
processing tools suitable for rapid correction and extraction of data contained
in three-dimensional fluorescence excitation-emission matrix (3DEEM) for real
time studies. 3DEEM was evaluated for direct quantification of Effluent Organic
Matter (EfOM) fractions in full-scale MBR bulk supernatant and permeate samples.
Principal Component Analysis (PCA) was used to investigate possible correlations
between conventional Lowry and Dubois methods, Liquid Chromatography coupled to
Organic Carbon and Organic Nitrogen Detection (LC-OCD-OND) and 3DEEM. 3DEEM data
were analyzed using the volume of fluorescence (Phi) parameter from the
Fluorescence Regional Integration (FRI) method. Two mathematical correlations
were established between LC-OCD-OND and 3DEEM data to quantify protein-like and
humic-like substances. These correlations were validated with supplementary data
from the initial full-scale MBR, and were checked with samples from other systems
(a second full-scale MBR, a full-scale conventional activated sludge (CAS) and a
laboratory-scale MBR). While humic-like correlation showed satisfactory
prediction for a second full-scale MBR and a CAS system, further studies are
required for protein-like estimation in other systems. This new approach offers
interesting perspectives for the on-line application of 3DEEM for EfOM
quantification (protein-like and humic-like substances), fouling prediction and
MBR process control.
PMID- 28414964
TI - Insights into the short-term effects of CeO2 nanoparticles on sludge dewatering
and related mechanism.
AB - As CeO2 nanoparticles (NPs) are used in many applications, the released particles
eventually enter wastewater treatment plants, influencing sludge dewatering and
increasing the disposal costs. We conducted tests to gain insight into the sludge
dewatering performance and the potential mechanism related to the distribution
and production of extracellular polymeric substances (EPS). In addition, we
conducted single-factor tests with six concentrations of CeO2 NPs in sequencing
batch reactors containing matured activated sludge. Overall, the specific
resistance to filtration (SRF) improved with an increase in the CeO2 NPs dosage.
The SRF significantly increased from 1.460 * 1012 to 1.632 * 1012 m/kg after the
addition of 5 mg/L CeO2 NPs (p < 0.05). The bound water content was enhanced from
2.43 to 2.75 kg/kg dry solid, indicating a deteriorated dewaterability. We found
that the increased EPS production, especially the dominant protein (r = 0.987, p
< 0.01), was correlated significantly with the SRF. This is ascribed to the
inhibited activity of leucyl aminopeptidase and the reduced adenosine 5'
triphosphate concentrations after exposure to CeO2 NPs. The fluorescence region
integration technique and protein secondary structures revealed the reasons for
the poor dewatering performance in the presence of CeO2 NPs. These are the
enhanced amount of soluble microbial by-product-like material and the low value
of the alpha-helix/(beta-sheet + random coil). These results could potentially
expand the knowledge on sludge dewatering in the presence of NPs.
PMID- 28414965
TI - Response to a mindful self-compassion intervention in teens: A within-person
association of mindfulness, self-compassion, and emotional well-being outcomes.
AB - As adolescence can be a stressful developmental stage, the purpose of this study
was to determine if a novel mindful self-compassion program would decrease
stress, depressive symptoms, and anxiety and increase resilience, gratitude, and
curiosity/exploration (positive risk-taking), and to ascertain if mindfulness and
self-compassion co-varied with these outcomes over time. Forty-seven adolescents
in the southeast U.S. enrolled in an 8-week mindful self-compassion course in
five cohorts. Measures were assessed at pre-intervention, post-intervention, and
6-week follow-up. Multilevel growth analyses revealed main effects of time on
perceived stress, resilience, curiosity/exploration and gratitude. Additionally,
both mindfulness and self-compassion co-varied with perceived stress and
depressive symptoms; mindfulness also co-varied with anxiety and self-compassion
co-varied with resilience and curiosity/exploration. Implications of these
findings are that this program has potential in decreasing stress and increasing
resilience and positive risk-taking. Future studies with a control group need to
be conducted to confirm these findings.
PMID- 28414966
TI - Modeling sleep and neuropsychiatric disorders in zebrafish.
AB - What are the molecular and cellular mechanisms that link neurological disorders
and sleep disturbances? The transparent zebrafish model could bridge this gap in
knowledge due to its unique genetic and imaging toolbox, and amenability to high
throughput screening. Sleep is well-characterized in zebrafish and key regulators
of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin
(Hcrt), whereas novel sleep regulating proteins are continually being identified,
such as Kcnh4a, Neuromedin U, and QRFP. Sleep deficiencies have been observed in
various zebrafish models for genetic neuropsychiatric disorders, ranging from
psychomotor retardation and autism to anxiety disorders. Understanding the link
between neuropsychiatric disorders and sleep phenotypes in zebrafish may
ultimately provide a platform for identifying therapeutic targets for clinical
trials in humans.
PMID- 28414967
TI - Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial
temporal lobe epilepsy.
AB - Patients with medically refractory epilepsy may benefit from resective epilepsy
surgery. However even the best centers experience surgical failures. It is
therefore important to find techniques that may aid in neurosurgical planning of
epileptic focus resection. Recordings of electrical brain activity with EEG
during seizures reveal abnormal cortical hypersynchronization. Between seizures
the EEG often shows interictal depolarizing phenomena such as spikes reflecting
an irritable focus of the brain. In the present study we investigated the effect
of intravenous remifentanil on the spike activity in the temporal neocortex and
hippocampus. We examined 65 patients with mesial temporal lobe epilepsy during
surgery, prior to resection. We used a 20-lead grid on the cortex and a 4-lead
strip in the lateral ventricle on the hippocampus. At least two 3-min periods of
ECoG were recorded - before and after remifentanil injection. In a number of
patients we examined the effect of repeated injections in order to estimate the
dose-response curve. We describe a significant effect of remifentanil on the
average spike activity with an increment from 16 spikes per minute at baseline to
36 spikes per minute after remifentanil injection (p<0.0001). The increase in
spike activity was typically seen after 40-50s. When mu-receptors were
antagonized with a preceding injection of naloxone, spike activity increased 25%
in response to remifentanil as opposed to 80% when remifentanil was preceded by
placebo. In only seven out of 59 patients did the injection of remifentanil
change the topographic location of the spike focus. Typically administration of
remifentanil led to a focus of increased spike count. Activity in other areas was
suppressed making the focus stand out from the background. Our observation that
remifentanil potentiates spike activity is in agreement with previous findings
from smaller studies. Furthermore, we were able to describe the pharmacodynamics
of the remifentanil effect on spike activity. Peri-operative provocation with
remifentanil may play a future role in guiding neurosurgical intervention during
epilepsy resection surgery.
PMID- 28414968
TI - Investigating the correlation between short-term effectiveness of VNS Therapy in
reducing the severity of seizures and long-term responsiveness.
AB - VNS (Vagus Nerve Stimulation) Therapy(r) is an adjunctive therapy for patients
with medically refractory epilepsy. The primary metric used to assess response to
any treatment for epilepsy is seizure frequency reduction as measured using
seizure diaries. In addition to seizure frequency, reduction in seizure severity
is clinically meaningful to patients and can be measured objectively. Analysis of
electro-encephalographic (EEG) signals has revealed that seizures are accompanied
by spatial synchronization of EEG electrodes that may persist for several minutes
after the seizure. A quantitative feature was obtained from EEG data around ictal
events collected during a 3-5day epilepsy monitoring unit (EMU) visit prior to
VNS implantation and following one month after VNS implant. This feature was
obtained from 15 patients who underwent implantation of the closed-loop
AspireSR(r) VNS Therapy System. We used this feature to first evaluate if
automated delivery of VNS at the time of seizure onset reduces the severity of
seizures in patients by reducing EEG spatial synchronization. We then explored
the correlation between the effectiveness of VNS in reducing the severity of
seizures and long-term (12 month follow-up) responsiveness using clinical metrics
of seizure frequency reduction. Results of application of this methodology to 103
pre-VNS and 102 post-VNS seizures revealed that automatic delivery of VNS Therapy
reduces ictal spatial synchronization (EEG-based quantitative feature) in
patients who responded (>=50% reduction in seizure frequency) to VNS Therapy.
This feature may be used as potential biomarker for predicting long-term response
to VNS Therapy.
PMID- 28414969
TI - Cytokines in the management of rotavirus infection: A systematic review of in
vivo studies.
AB - OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus
vaccines are effective against severe rotavirus gastroenteritis, but have lower
efficacy in low income countries in Africa. Anti-rotavirus treatment is not
available. This study reviews the literature of animal studies evaluating whether
cytokine mediated pathways of immune activation could improve rotavirus therapy.
METHODS: We performed a systematic review of articles in English published from
2010 to 2016 reporting agents with in vivo antirotavirus activity for the
management of rotavirus infection. The search was carried in PubMed, EMBASE,
Scopus and Web of Science. Animal experiments where cytokines were investigated
to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869
publications were identified. Of these, 19 pertained the objectives of the
review, and 11 articles described the effect of probiotics/commensals on
rotavirus infection and immune responses in animals. Eight further in vivo
studies evaluated the immunomodulating effects of herbs, secondary metabolites
and food-derived products on cytokine responses of rotavirus-infected animals.
Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon
gamma (IFN-gamma), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10)
cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus
infection through suppression of inflammation by viral inhibition. CONCLUSION:
Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding
and/or replication in animal models. Th1/Th2 cytokine responses have optimal
immunomodulating effects to reduce rotavirus diarrhoea and enhance immune
responses in experimental rotavirus infection.
PMID- 28414970
TI - Understanding deceptive intentions behind pointing gestures in 12-15-month-old
infants.
AB - We examined the comprehension of deceptive intentions revealed in searching task
in infancy, on the theoretical basis of natural pedagogy and epistemic trust. The
main findings showed that 12-15-month-old infants are able to discriminate the
reliable and the deceptive actions of adults, but they do not generalize their
previous experience in connection with a novel person, who is treated as a new
reliable source of information.
PMID- 28414971
TI - Influence of sulfur fumigation on the chemical profiles of Atractylodes
macrocephala Koidz. evaluated by UFLC-QTOF-MS combined with multivariate
statistical analysis.
AB - In the present study, the chemical compositions of Atractylodes macrocephala
Koidz. (AMK) were analyzed systematically and influence of sulfur fumigation on
the chemical profiles was evaluated by ultrafast flow liquid chromatography
coupled with quadrupole-time-of-flight mass spectrometry (UFLC-QTOF-MS) combined
with multivariate statistical analysis. 52 components were detected from non
fumigated AMK (NF-AMK) and 28 components were newly produced after sulfur
fumigation, out of which 59 major peaks were identified. The concentrations of 20
compounds significantly decreased and 37 compounds obviously increased. The
potential structural transformation mechanism of terpenoids was explored to
illustrate the correlation of the components contents before and after sulfur
fumigation. Eight sulfur-containing/dehydrated-integrated atractylenolides that
evolved from the NF-AMK were screened out as potential characteristic chemical
markers to examine the post-harvest handling procedures of commercial AMK with
excessive sulfur fumigation and maintain consistent quality.
PMID- 28414972
TI - An LC-MS/MS method for quantification of AC0010, a novel mutant-selective
epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human
plasma and the application to a pharmacokinetic study.
AB - AC0010 is an irreversible, mutant-selective EGFR inhibitor that effectively
inhibits EGFR active and T790M resistance mutations in non-small cell lung cancer
(NSCLC). A sensitive ultra-performance liquid chromatography - tandem mass
spectrometry (UPLC-MS/MS) method was developed and fully validated for
determining AC0010 and its metabolites in human plasma. The samples were purified
by solid-phase extraction (SPE) columns and separated on a BEH C18 column.
Electrospray ionization (ESI) in positive ion mode and multiple reaction
monitoring (MRM) were used to monitor the ion transitions of AC0010 (m/z 488
>257) and its metabolites M1 (m/z 474->403), M2 (m/z 504->487), M4 (m/z 434
>377), M7 (m/z 490->405), MII-1 (m/z 651->434) and MII-2 (m/z 609->434). The
results revealed that the method had excellent selectivity and linearity. Intra
day and inter-day precisions (in terms of relative standard deviation, RSD) were
lower than 14.4% and the accuracies (in terms of relative error, RE) were within
the range of +/-10.3% for all the analytes. The lower limit of quantification
(LLOQ), stability, matrix effect and extraction recovery were also validated and
satisfied the criteria of validation. Finally, the method was successfully
applied to a pharmacokinetic study of NSCLC patients after a single oral dose of
350mg of AC0010.
PMID- 28414973
TI - Regulation of antibiotic-resistance by non-coding RNAs in bacteria.
AB - Antibiotic resistance genes are commonly regulated by sophisticated mechanisms
that activate gene expression in response to antibiotic exposure. Growing
evidence suggest that cis-acting non-coding RNAs play a major role in regulating
the expression of many resistance genes, specifically those which counteract the
effects of translation-inhibiting antibiotics. These ncRNAs reside in the 5'UTR
of the regulated gene, and sense the presence of the antibiotics by recruiting
translating ribosomes onto short upstream open reading frames (uORFs) embedded in
the ncRNA. In the presence of translation-inhibiting antibiotics ribosomes arrest
over the uORF, altering the RNA structure of the regulator and switching the
expression of the resistance gene to 'ON'. The specificity of these
riboregulators is tuned to sense-specific classes of antibiotics based on the
length and composition of the respective uORF. Here we review recent work
describing new types of antibiotic-sensing RNA-based regulators and elucidating
the molecular mechanisms by which they function to control antibiotic resistance
in bacteria.
PMID- 28414974
TI - Bilirubin nanoparticle preconditioning protects against hepatic ischemia
reperfusion injury.
AB - Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver
transplantation and resection, despite continuing efforts to prevent it.
Accumulating evidence suggests that bilirubin possesses antioxidant, anti
inflammatory and anti-apoptotic properties. However, despite obvious potential
health benefits of bilirubin, its clinical applications are limited by its poor
solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of
polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate
whether BRNPs protect against IRI in the liver by preventing oxidative stress.
BRNPs exerted potent antioxidant and anti-apoptotic activity in primary
hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species
(ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound
protective effects against hepatocellular injury by reducing oxidative stress,
pro-inflammatory cytokine production, and recruitment of neutrophils. They also
preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our
findings indicate that BRNP preconditioning provides a simple and safe approach
that can be easily monitored in the blood like endogenous bilirubin, and could be
a promising strategy to protect against IRI in a clinical setting.
PMID- 28414975
TI - Fullerene-doped polyaniline as new redox nanoprobe and catalyst in
electrochemical aptasensor for ultrasensitive detection of Mycobacterium
tuberculosis MPT64 antigen in human serum.
AB - Tuberculosis caused by Mycobacterium tuberculosis (MTB) is still a major threat
to global public health. However, the existing methods for MTB detection are
usually complicated and time consuming with unsatisfactory sensitivity and
specificity. In this work, a relatively simple and ultrasensitive electrochemical
aptasensor based on novel signal generation and amplification was constructed for
the determination of MTB antigen MPT64. The coil-like fullerene (C60)-doped
polyaniline (C60-PAn) nanohybrids with large surface area, abundant active groups
and excellent electric performance were synthesized and used both as new redox
nanoprobe and catalyst for the generation and amplification of electrochemical
signal for the first time. Then gold nanoparticles decorated C60-PAn
nanocomposites (GNPs-C60-PAn) were labeled with signal aptamer to form the tracer
label. After the sandwich reaction of target MPT64 antigen between capture
aptamer and the tracer label, a distinguishing detection signal of C60-PAn would
be observed. Moreover, the detection signal could be enormously enhanced towards
the efficient electrocatalytic oxidation of ascorbic acid based on C60-PAn,
resulting in further improvement of the sensitivity. With the excellent redox and
electrocatalytic activity of C60-PAn, a wide detection linear range from 0.02 to
1000 pg/mL was obtained with a detection limit of 20 fg/mL for MPT64. The
proposed aptasensor showed high selectivity to target antigen compared with
possible interfering substances. More importantly, it also exhibited excellent
specificity and sensitivity for MPT64 detection in serum samples of tuberculosis
patients, which provided a rapid and efficient detection method for MTB
infection.
PMID- 28414976
TI - Glucose-sensitive self-healing hydrogel as sacrificial materials to fabricate
vascularized constructs.
AB - A major challenge in tissue engineering is the lack of proper vascularization.
Although various approaches have been used to build vascular network in a tissue
engineering construct, there remain some drawbacks. Herein, a glucose-sensitive
self-healing hydrogel are employed as sacrificial materials to fabricate branched
tubular channels within a construct. The hydrogel composes of mainly reversibly
crosslinked poly(ethylene glycol) diacrylate and dithiothreitol with borax as the
glucose-sensitive motif. The hydrogel is injectable and mechanically strong after
injection. Moreover, it can be rapidly removed by immersion in the cell culture
medium. To show the feasibility in building a vascularized tissue construct, the
designed branching vascular patterns of the glucose-sensitive hydrogel are
extruded and embedded in a non glucose-sensitive hydrogel containing neural stem
cells. Vascular endothelial cells seeded in the lumen of the channels by
perfusion can line the channel wall and migrate into the non-sacrificial hydrogel
after 3 days. In long-term (~14 days), the endothelial cells form capillary-like
structure (vascular network) while neural stem cells form neurosphere-like
structure (neural development) in the construct, revealing the morphology of "a
vascularized neural tissue". The novel sacrificial materials can create
complicated but easily removable structure for building a vascularized tissue
construct particularly a neurovascular unit.
PMID- 28414977
TI - Design of the magnetic homonuclear bonds boron nitride nanosheets using DFT
methods.
AB - Design and characterization of the structural, electronic, and magnetic
properties of armchair boron-nitride, BN (B27N27H18), nanosheets were performed
by means of density functional theory all-electron calculations. The HSEh1PBE-GGA
method together with 6-31G(d) basis sets were used. Non-stoichiometric B30N24H18
and B24N30H18 compositions: rich in boron or nitrogen atoms, forming homonuclear
B or N bonds, respectively, were chosen. The obtained results reveal that these
BN nanosheets reach structural stability in the anionic form, where semiconductor
and magnetic behaviors are promoted. Effectively, the HOMO-LUMO gap is of 2.03
and 2.39eV, respectively and the magnetic moments are of 1.0 magneton bohrs,
coming from the boron atoms in both systems. The rich in boron nanosheets present
high-polarity, either in the gas phase or embedded in aqueous mediums like water,
as well as low chemical reactivity, signifying potential applicability in the
transportation of pharmaceutical species in biological mediums. These systems are
also promising for the design of electronic devices, because they possess low
work functions, mainly arising from the homonuclear boron or nitrogen bond
formation.
PMID- 28414978
TI - Investigation on the relationship between solubility of artemisinin and
polyvinylpyrroli done addition by using DAOSD approach.
AB - In this work, we investigated the influence of polyvinylpyrrolidone (PVP) on the
solubility of artemisinin in aqueous solution by using quantitative 1H NMR.
Experimental results demonstrate that about 4 times of incremental increase
occurs on the solubility of artemisinin upon introducing PVP. In addition, dipole
dipole interaction between the ester group of artemisinin and the amide group of
N-methylpyrrolidone (NMP), a model compound of PVP, is characterized by two
dimensional (2D) correlation FTIR spectroscopy with the DAOSD (Double
Asynchronous Orthogonal Sample Design) approach developed in our previous work.
The observation of cross peaks in a pair of 2D asynchronous spectra suggests that
dipole-dipole interaction indeed occurs between the ester group of artemisinin
and amide group of NMP. Moreover, the pattern of cross peaks indicates that the
carbonyl band of artemisinin undergoes blue-shift while the bandwidth and
absorptivity increases via interaction with NMP, and the amide band of NMP
undergoes blue-shift while the absorptivity increases via interaction with
artemisinin. Dipole-dipole interaction, as one of the strongest intermolecular
interaction between artemisinin and excipient, may play an important role in the
enhancement of the solubility of artemisinin in aqueous solution.
PMID- 28414979
TI - Role of EGF on in situ culture of equine preantral follicles and metabolomics
profile.
AB - The effects of epidermal growth factor (EGF) concentrations (0, 10, 50, and
100ng/ml) on in vitro culture (IVC) of equine preantral follicles were evaluated
using histology, estradiol and reactive oxygen species (ROS) production and
metabolomics. After IVC, the percentage of normal follicles was lower (P<0.05)
for all treatments when compared to non-cultured control. EGF 50ng/ml treatment
had more (P<0.05) normal follicles at Day 7 of culture when compared with EGF 0
and 100ng/ml. EGF 50ng/ml had more (P<0.05) developing follicles than the 0ng/ml
and 10ng/ml EGF treatments. Follicular and oocyte diameters were greater (P<0.05)
with EGF 50ng/ml than the other cultured treatments, but similar (P>0.05) to the
non-cultured control. From Day 1 to Day 7 estradiol production increased (P<0.05)
in all EGF treatments. EGF 50ng/ml was the only treatment that maintained ROS
production through IVC. Metabolomics profiles of the spent media indicated that
eleven ions from variable influence in the projection (VIP) scores were higher
represented in the EGF 50ng/ml treatment. In conclusion, EGF 50ng/ml treatment
maintained follicle survival and ROS production, and promoted activation of
cultured equine preantral follicles enclosed in ovarian tissue.
PMID- 28414980
TI - Fluorescence and circular dichroism studies on the accessibility of tryptophan
residues and unfolding of a jacalin-related alpha-d-galactose-specific lectin
from mulberry (Morus indica).
AB - MLGL (Mulberry Latex Galactose-specific Lectin) is an alpha-d-galactose binding
lectin isolated from the latex of mulberry (Morus indica) tree and contains two
tryptophan residues in each of its subunits. The fluorescence emission maximum of
native MLGL seen at 326nm shifts to 350nm upon incubation with 6M guanidinium
thiocyanate (Gdn.SCN), suggesting that the tryptophans are located inside the
hydrophobic core of the protein and become fully exposed upon denaturation.
Fluorescence quenching studies revealed that the neutral acrylamide exhibits the
highest quenching, with ~33% of total fluorescence in the native protein being
quenched at a quencher concentration of 0.5M, whereas iodide (~24%) and cesium
(~4%) ions showed significantly lower quenching. With the denatured protein,
acrylamide quenching involves both dynamic and static processes as evident from
an upward curving Stern-Volmer plot. Time-resolved fluorescence studies showed
two lifetime components of 3.7ns and 1.3ns for the native protein, while three
lifetime components were observed for the denatured protein. MLGL showed high
resistance to urea (up to 8M) and guanidine hydrochloride (up to 6M), whereas
treatment with 6M Gdn.SCN completely denatured the protein, via a broad sigmoidal
transition with a transition midpoint at ~3.75M. Circular dichroism studies and
hemagglutination assays showed that the secondary and tertiary structures as well
as lectin activity of MLGL were unaffected up to 70 degrees C. Additionally, pH
dependent studies showed that the secondary structure of MLGL is unaltered in the
pH range 6.2 to 8.5, but a decrease in lectin activity is observed (~50%) at
pH6.2.
PMID- 28414981
TI - Claims in vapour device (e-cigarette) regulation: A Narrative Policy Framework
analysis.
AB - BACKGROUND: The electronic cigarette or e-cigarette (vapour device) is a consumer
product undergoing rapid growth, and governments have been adopting regulations
on the sale of the devices and their nicotine liquids. Competing claims about
vapour devices have ignited a contentious debate in the public health community.
What claims have been taken up in the state arena, and how have they possibly
influenced regulatory outcomes? METHODS: This study utilized Narrative Policy
Framework to analyze the claims made about vapour devices in legislation
recommendation reports from Queensland Australia, Canada, and the European Union,
and the 2016 deeming rule legislation from the United States, and examined the
claims and the regulatory outcomes in these jurisdictions. RESULTS: The vast
majority of claims in the policy documents represented vapour devices as a
threat: an unsafe product harming the health of vapour device users, a gateway
product promoting youth tobacco uptake, and a quasi-tobacco product impeding
tobacco control. The opportunity for vapour devices to promote cessation or
reduce exposure to toxins was very rarely presented, and these positive claims
were not discussed at all in two of the four documents studied. CONCLUSION: The
dominant claims of vapour devices as a public health threat have supported
regulations that have limited their potential as a harm reduction strategy.
Future policy debates should evaluate the opportunities for vapour devices to
decrease the health and social burdens of the tobacco epidemic.
PMID- 28414982
TI - Relation of positive fluid balance to the severity of renal impairment and
recovery among ST elevation myocardial infarction complicated by cardiogenic
shock.
AB - PURPOSE: We analyzed the relationship between a positive fluid balance and its
persistence over time on acute kidney injury (AKI) development, severity and
resolution among ST elevation myocardial infarction (STEMI) patients complicated
by cardiogenic shock. METHODS: We retrospectively studied the cumulative fluid
balance intake and output at 96h following hospital admission in 84 consecutive
adult patients with STEMI complicated by cardiogenic shock. The cohort was
stratified into two groups, based on the presence or absence of positive fluid
balance on day 4. Patients' records were assessed for the development of AKI, AKI
severity and recovery. RESULTS: Patients having positive fluid balance were more
likely to develop a more severe AKI stage (52% vs. 13%; p<0.001), were less
likely to have recovery of their renal function (29% vs. 75%, p=0.001), and
demonstrated positive correlation between the amount of fluid accumulated and the
rise in serum creatinine (R=0.42, p=0.004). For every 1l increase in positive
fluid balance, the adjusted possibility for recovery of renal function decreased
by 21% (OR=0.796, 95% CI 0.67-0.93; p=0.006). CONCLUSIONS: A positive fluid
balance was strongly associated with higher stage AKI and lower rate of AKI
recovery in STEMI complicated by cardiogenic shock.
PMID- 28414983
TI - A randomised controlled trial in comparing maternal and neonatal outcomes between
hands-and-knees delivery position and supine position in China.
AB - BACKGROUND: the supine position is the most frequently offered for birth delivery
in China and many other countries, but the hands-and-knees position is now
gaining prominence with doctors in China. This study aims to examine the
differences in maternal and neonatal outcomes among low-risk women who gave birth
either in the hands-and-knees position or the supine position. METHODS: a
randomised controlled trial was conducted in 11 hospitals in China from May to
December in 2012. In total, 1400 women were recruited and randomly allocated to
either the experimental group (n=700, 446 completed the protocol) who delivered
in hands-and-knees position and the control group (n=700, 440 completed the
protocol) who delivered in supine position. Women who could not maintain the
randomised position during the second stage of labour were allowed to withdraw
from the study. The primary maternal outcome measured was rate of episiotomy.
Secondary outcomes included degree of perineum laceration, rate of emergency
caesarean section, rate of shoulder dystocia, and duration of labour, postpartum
bleeding, neonatal Apgar score, and the rate of neonatal asphyxia. Because
outcome data were only collected for women who gave birth in the randomised
position, per-protocol analyses were used to compare groups. The primary outcome,
episiotomy, was also compared between groups using logistic regression adjusting
for maternal age,gestational age at birth, whether the woman was primiparous, the
process of second stage of labour and birthweight. FINDINGS: as compared with the
control group, the experimental group had lower rates of episiotomy and second
degree perineum laceration (including episiotomy), and higher rates of intact
perineum and first-degree perineum laceration, with a longer duration of second
stage of labour. No significant differences were found in the amount of
postpartum bleeding, shoulder dystocia, neonatal asphyxia and neonatal Apgar
scores at 1minute and 5minutes. Adjusted for maternal age, gestational age,
parity, duration of second stage of labour and birth weight, the hands-and-knees
position reduced the need for episiotomy (OR=0.024, p<0.001). CONCLUSIONS: this
study provided evidence that women who could maintain the hands-and-knees
position during the second stage of labour had lower rates of episiotomy and
second-degree perineum laceration (including episiotomy). Both midwives and
obstetricians are suggested to learn the skills to assist women with delivery in
this position.
PMID- 28414984
TI - A fully synthetic lung model for wound-ballistic experiments-First results.
AB - PURPOSE: Today, synthetic models have all but replaced animal and corpse models
in examining damage to soft-tissues and skeletal structures by ballistic trauma.
As, however, non-solid organs such as the lungs, have not been able to be
replaced by a fully synthetic model we attempted to create such a model. MATERIAL
AND METHODS: 20% ordnance gelatine was frothed with a household mixer and cooled
to stable foam. Several of these foam blocks were then stuck together with liquid
gelatine and placed between 10% gelatine blocks. As controls, we embedded pig
lungs in gelatine and compared the wound channels seen in computed tomography
created upon shooting with 9mm Luger. RESULTS: The fully synthetic models
displayed radiological and physical densities comparable to real lungs. The wound
profile characteristics of the fully synthetic lung models were very similar to
the semisynthetic swine-gelatine models regarding the permanent wound cavity.
Furthermore, in both semi- and fully synthetic models we detected a ring
surrounding the permanent wound channel, most likely representing the remnants of
the temporary wound cavity. CONCLUSION: Our results indicate that this fully
synthetic lung model is a viable substitute for ballistic experiments on lungs.
We believe that further research on the temporary wound channel in lungs is
possible with this model in order to provide more insight into the effect of
ballistic trauma to the lungs not seen otherwise.
PMID- 28414985
TI - Sharp and blunt force trauma concealment by thermal alteration in homicides: An
in-vitro experiment for methodology and protocol development in forensic
anthropological analysis of burnt bones.
AB - Burning of human remains is one method used by perpetrators to conceal fatal
trauma and expert opinions regarding the degree of skeletal evidence concealment
are often disparate. This experiment aimed to reduce this incongruence in
forensic anthropological interpretation of burned human remains and implicitly
contribute to the development of research methodologies sufficiently robust to
withstand forensic scrutiny in the courtroom. We have tested the influence of
thermal alteration on pre-existing sharp and blunt trauma on twenty juvenile
sheep radii in the laboratory using an automated impact testing system and an
electric furnace. The testing conditions simulated a worst-case scenario where
remains with pre-existing sharp or blunt trauma were exposed to burning with an
intentional vehicular fire scenario in mind. All impact parameters as well as the
burning conditions were based on those most commonly encountered in forensic
cases and maintained constant throughout the experiment. The results have shown
that signatures associated with sharp and blunt force trauma were not masked by
heat exposure and highlights the potential for future standardization of fracture
analysis in burned bone. Our results further emphasize the recommendation given
by other experts on handling, processing and recording burned remains at the
crime scene and mortuary.
PMID- 28414986
TI - Modelling dental implant extraction by pullout and torque procedures.
AB - Dental implants extraction, achieved either by applying torque or pullout force,
is used to estimate the bone-implant interfacial strength. A detailed description
of the mechanical and physical aspects of the extraction process in the
literature is still missing. This paper presents 3D nonlinear dynamic finite
element simulations of a commercial implant extraction process from the mandible
bone. Emphasis is put on the typical load-displacement and torque-angle
relationships for various types of cortical and trabecular bone strengths. The
simulations also study of the influence of the osseointegration level on those
relationships. This is done by simulating implant extraction right after
insertion when interfacial frictional contact exists between the implant and
bone, and long after insertion, assuming that the implant is fully bonded to the
bone. The model does not include a separate representation and model of the
interfacial layer for which available data is limited. The obtained relationships
show that the higher the strength of the trabecular bone the higher the peak
extraction force, while for application of torque, it is the cortical bone which
might dictate the peak torque value. Information on the relative strength
contrast of the cortical and trabecular components, as well as the progressive
nature of the damage evolution, can be revealed from the obtained relations. It
is shown that full osseointegration might multiply the peak and average load
values by a factor 3-12 although the calculated work of extraction varies only by
a factor of 1.5. From a quantitative point of view, it is suggested that, as an
alternative to reporting peak load or torque values, an average value derived
from the extraction work be used to better characterize the bone-implant
interfacial strength.
PMID- 28414987
TI - Effects of different radiation doses on the microhardness, superficial
morphology, and mineral components of human enamel.
AB - OBJECTIVE: To evaluate the effects of three different radiotherapy doses (20, 40,
and 70Gy) on the microhardness, superficial morphology, and mineral content
(based on Ca and P values) of three different depths of human enamel (cervical,
middle, and occlusal). DESIGN: Thirty-four third molars were cut, separated, and
prepared. Microhardness samples (n=30) were embedded in acrylic resin and then
polished, and depths were delimited. Microhardness tests were performed on
cervical, middle, and occlusal enamel pre- and post-radiotherapy with a load of
50g for 30s. For the scanning electron microscopy (SEM) analysis (n=4) and energy
dispersive X-ray spectroscopy (EDS) (n=12), samples were fixed in a 3%
glutaraldehyde solution, washed in 0.1M cacodylate solution, and dehydrated in
crescent concentrations of ethanol. Microhardness data were tested for
significant differences using a two-way analysis of variance (ANOVA) and Tukey's
test (p<0.05), while SEM and EDS were evaluated qualitatively. RESULTS: The
results showed a decrease in microhardness values only in the cervical enamel,
regardless of the radiation dose used; no morphological or mineral change was
observed. CONCLUSION: Radiotherapy can affect the microhardness values of only
cervical enamel without compromising the morphological or mineral (Ca and P)
content at any depth.
PMID- 28414988
TI - Response of mandibular condyles of juvenile and adult rats to abnormal occlusion
and subsequent exemption.
AB - OBJECTIVE: The adaptation capacities of the mandibular condyle in response to
mechanical stimuli might be different between juveniles and adults, but has not
been compared. This study aimed to investigate whether abnormal molar occlusion
and subsequent molar extraction could lead to different remodeling responses in
the mandibular condyles of juvenile and adult rats. METHODS: Abnormal molar
occlusion (AMO) was established in the 5- and 16-wk old rats by moving their
maxillary left and mandibular right third molars distally. AMO was removed in the
molar extraction group at 4 weeks but remained in the AMO group. All rats were
sacrificed at 8 weeks. Micro-computed tomography, histomorphology,
immunohistochemistry and real-time PCR were adopted to evaluate the remodeling of
condylar subchondral bone. RESULTS: Condylar subchondral bone loss and increased
osteoclastic activities were observed in both juvenile and adult AMO groups,
while increased osteoblastic activities were only seen in the juvenile AMO group.
Decreased bone mineral density, bone volume fraction and trabecular thickness,
but increased trabecular separation, number and surface of osteoclasts and mRNA
levels of TRAP, cathepsin-K, RANKL in the juvenile AMO group were all reversed
after molar extraction (all P<0.05). However, these parameters showed no
difference between adult AMO and extraction groups (all P>0.05). CONCLUSIONS:
Abnormal molar occlusion led to degenerative remodeling in the mandibular
condyles of both juvenile and adult rats, while exemption of abnormal occlusion
caused significant rescue of the degenerative changes only in the juvenile rats.
PMID- 28414990
TI - Medical outcomes associated with prescription opioid abuse via oral and non-oral
routes of administration.
AB - BACKGROUND: Prescription opioid abuse and misuse is a serious and growing public
health issue. While the most common form of abuse is swallowing intact
tablets/capsules, some abusers manipulate, or tamper with, these medications by
altering the dosage form to allow for non-oral routes of administration (e.g.,
injection, inhalation) in order to achieve more rapid or enhanced psychoactive
effects. Because administration of opioids via non-oral routes results in greater
systemic availability and more rapid central nervous system penetration, we
hypothesized that death and major medical outcomes occur more frequently with non
oral routes compared to oral route alone. METHODS: This retrospective cohort
study analyzed data from the Researched Abuse, Diversion and Addiction-Related
Surveillance (RADARS) System Poison Center Program to investigate relative risk
of prescription opioid abuse via oral and non-oral routes. RESULTS: While the
oral route was the most commonly reported route of abuse (64.0%), non-oral routes
were reported in 14.6% exposures and unknown routes in 21.4% exposures. The
relative risk of an exposure resulting in death or major effect was 2.43 (95% CI
1.97, 2.99) if non-oral routes were reported compared to exposures involving oral
route only. CONCLUSION: Analysis of acute health events recorded by poison
centers indicates that death or major effects are twice as likely to occur with
intentional abuse of prescription opioids via non-oral routes of administration
than ingestion alone. Effective interventions to prevent abuse via non-oral
routes of solid dosage forms of prescription opioids, such as abuse-deterrent
formulations could have a significant public health impact.
PMID- 28414991
TI - Modeling the detection efficiency of an HP-Ge detector for use in boron neutron
capture therapy.
AB - The multi-foil method is commonly used to determine upon an energy spectrum of
neutrons in boron neutron capture therapy. The method requires to measure the
radioactivation of the foils. This study develops a simple modeling procedure of
a high-purity Ge detector, which is used to measure the radioactivation, in order
to calculate the detection efficiency with GEANT4. By changing four parameters
from their manufacturing specifications of the detector, the simulated detection
efficiency is able to reproduce the actual detection efficiency.
PMID- 28414989
TI - Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression
and tricyclic antidepressants.
AB - INTRODUCTION: Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol
use disorder (AUD) and depression is suggested, very little information on a
direct interaction between alcohol and these receptors is available. METHODS: In
this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal
model of depression, were exposed to alcohol vapor 3h daily for 10days (blood
alcohol concentration ~150mg%) followed by daily injection of 10mg/kg of
imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or
nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals
were tested for open field locomotor activity (OFLA) and forced swim test (FST)
and were sacrificed 2h later for measurement of alpha-2 ARs densities in the
frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand.
RESULTS: Chronic alcohol treatment increased the immobility in the FST, without
affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive
like behavior in Wistar rats and an exacerbation of this behavior in WKY rats.
Alcohol treatment also resulted in an increase in cortical but not hippocampal
alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of
alcohol were completely blocked by IMP and NOMI and the neurochemical effects
(increases in alpha-2 ARs) were significantly attenuated by both drugs in both
strains. CONCLUSIONS: The results suggest a role for cortical alpha-2 ARs in
alcohol withdrawal-induced depression and that selective subtype antagonists of
these receptors may be of adjunct therapeutic potential in AUD-depression co
morbidity.
PMID- 28414993
TI - Chikungunya virus infections: time to act, time to treat.
AB - Chikungunya virus (CHIKV) is a re-emerging alphavirus that caused massive
outbreaks of Chikungunya fever in several countries and regions in Africa, Asia
and more recently in Central and South America. An acute CHIKV infection is
usually associated with fever and arthritis and it is rarely fatal. However, 15
60% of patients suffer from chronic polyarthralgia for weeks, months or even for
several years after the acute infection. There are currently no vaccines or
antivirals available for the prevention or treatment of CHIKV infections. The
development of potent and safe antivirals for prophylaxis (e.g., during travel to
CHIKV-endemic regions) and treatment of CHIKV infections is urgently needed. We
here review some of the recently reported CHIKV inhibitors, both directly-acting
and host-targeting compounds.
PMID- 28414992
TI - Airway proteases: an emerging drug target for influenza and other respiratory
virus infections.
AB - To enter into airway epithelial cells, influenza, parainfluenza- and
coronaviruses rely on host cell proteases for activation of the viral protein
involved in membrane fusion. One protease, transmembrane protease serine 2
(TMPRSS2) was recently proven to be crucial for hemagglutinin cleavage of some
human influenza viruses. Since the catalytic sites of the diverse serine
proteases linked to influenza, parainfluenza- and coronavirus activation are
structurally similar, active site inhibitors of these airway proteases could have
broad therapeutic applicability against multiple respiratory viruses.
Alternatively, superior selectivity could be achieved with allosteric inhibitors
of TMPRSS2 or another critical protease. Though still in its infancy, airway
protease inhibition represents an attractive host-cell targeting approach to
combat respiratory viruses such as influenza.
PMID- 28414994
TI - Adapting the Body Appreciation Scale-2 for Children: A psychometric analysis of
the BAS-2C.
AB - Positive body image among adults is related to numerous indicators of well-being.
However, no research has explored body appreciation among children. To facilitate
our understanding of children's positive body image, the current study adapts and
validates the Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a) for
use with children. Three hundred and forty-four children (54.4% girls) aged 9-11
completed the adapted Body Appreciation Scale-2 for Children (BAS-2C) alongside
measures of body esteem, media influence, body surveillance, mood, and dieting. A
sub-sample of 154 participants (62.3% girls) completed the questionnaire 6-weeks
later to examine stability (test-retest) reliability. The BAS-2C displayed a
unidimensional factor structure and evidence of internal consistency, test-retest
reliability, and construct, criterion-related, and incremental validity.
Additionally, the results suggest adaptive properties of body appreciation for
body-related and emotional well-being among children. The BAS-2C could serve as
an essential component within research to understand and estimate children's
positive body image.
PMID- 28414995
TI - Case report of an intracaval leiomyomatosis 10 months after complete
hysterectomy.
AB - INTRODUCTION: Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor,
usually found in women with tumors of the reproductive organs, such as uterus
myomatosous. Surgically, this case belies the call for sternotomy and two-stage
surgery in caval IVL extending to the right atrium: we suggest one-stage median
laparotomy as a minimal procedure with maximal benefit. PRESENTATION OF CASE: We
present the case of a 60-year-old postmenopausal woman with suspected intravenous
leiomyomatosis of the right internal iliac vein. The patient had undergone
hysterectomy and bilateral adnexectomy for uterus myomatosous in September 2015,
where an IVL limited to the veins of the uterus and the right adnex had been
diagnosed. No further medical treatment had been implemented. IVL of the inferior
vena cava was diagnosed when a CT scan of the abdomen was performed due to an
infected abdominal seroma in June 2016. Although histologically benign, we found
this case of IVL to be clinically aggressive because of its expansion to the
heart. This may lead to thromboembolic complications (e.g. pulmonary embolism) or
signs of right sided cardiac failure. The patient was asymptomatic, but because
of the extension of the intracaval thrombus to the heart, we decided to operate
and performed thrombectomy via a median laparotomy. The patient left the hospital
shortly after on newly started oral anticoagulation. DISCUSSION: For caval IVL
without intracardiac attachment, the extraction via laparotomy without sternotomy
is the treatment of choice. It calls for an interdisciplinary approach and
careful surgical planning. CONCLUSION: There is no inherent need for sternotomy
in IVL extending to the right atrium. A one-year follow-up with sonographic
control is advised. Medium term oral anticoagulation should be considered. This
work has been reported in line with the SCARE criteria Agha et al. (2016). The
SCARE Statement: Consensus-based surgical case report guidelines. Agha RA, Fowler
AJ, Saeta A, Barai I, Rajmohan S, Orgill DP; SCARE Group. Int J Surg. 2016
Oct;34:180-186 [1].
PMID- 28414996
TI - A case of multiple synchronous quadruple cancers of the stomach, sigmoid colon,
rectum, and pancreas.
AB - INTRODUCTION: Multiple primary neoplasms are relatively rare, but their incidence
has increased because of aging and improvements in diagnostic imaging.
PRESENTATION OF CASE: A 67-year-old man presented with epigastric pain. On upper
gastrointestinal endoscopy, an ulcer was seen at the gastric angle, and biopsy
showed moderately differentiated adenocarcinoma (AC). Colonoscopy demonstrated a
15-mm lesion in the sigmoid colon and a submucosal lesion in the lower rectum.
The biopsy showed well differentiated AC and neuroendocrine tumor (NET). In
addition, abdominal CT and MRI showed a 14-mm nodular lesion in the pancreatic
body suggesting pancreatic duct cancer. Based on the above findings, four
synchronous cancers, including the pancreas, stomach, sigmoid colon and rectum,
were diagnosed, and surgery was performed. A midline incision was made in the
upper abdomen, and a distal gastrectomy, pancreatic body and tail resection, and
sigmoidectomy were performed. Trans-anal tumor resection was performed for the
rectal lesion. Histopathology showed invasive pancreatic duct cancer, moderately
differentiated AC of the stomach, moderately differentiated AC of the sigmoid
colon, and NET G1 of the rectum. The patient had no postoperative complications,
4 years 3 months after resection, and he was disease-free from all of the
cancers. DISCUSSION: The strategy of perioperative diagnosis and treatment for
multiple primary tumors is usually difficult. This process was performed by
consulting a cancer board, which could be useful as a practice guideline.
CONCLUSION: This patient in whom four tumors were completely resected at the same
time and who has had a good clinical course was reported.
PMID- 28414997
TI - Successful treatment of nonocclusive mesenteric ischemia after aortic valve
replacement with continuous arterial alprostadil infusion: A case report.
AB - INTRODUCTION: Nonocclusive mesenteric ischemia (NOMI) after surgery has an
extremely poor prognosis with a mortality rate of 30-100%. We report a patient
with NOMI following aortic valve replacement who failed to improve despite
continuous intra-arterial infusion of papaverine, but was successfully treated
with alprostadil (prostaglandin E1 [PGE1]) infusion. PRESENTATION OF CASE: The
patient is a 77-year-old man who underwent aortic valve replacement. Due to
elevated serum lactate levels five hours after intensive care unit admission,
superior mesenteric arteriography was performed, establishing the diagnosis of
NOMI. Although continuous intra-arterial infusion of papaverine was begun,
lactate levels remained elevated. Repeat angiography and laparotomy revealed
extensive ischemic changes of the intestine. The vasodilator was changed to PGE1,
which improved arterial spasm. The patient ultimately needed an ileocecal
resection, but the extent of the resection was limited with concomitant PGE1
administration. DISCUSSION: In the present patient, although NOMI was
unresponsive to appropriate treatment including intra-arterial infusion of
papaverine, continuous intra-arterial infusion of PGE1 salvaged most of the
intestine. CONCLUSIONS: In a patient with recurrent NOMI despite appropriate
treatment including intra-arterial infusion of papaverine, continuous intra
arterial infusion of PGE1 may limit the extent of intestinal resection needed.
Continuous intra-arterial infusion of PGE1 may be a useful treatment for patients
with refractory NOMI.
PMID- 28414998
TI - A qualitative study on using concept maps in problem-based learning.
AB - BACKGROUND: The visual arts, including concept maps, have been shown to be
effective tools for facilitating student learning. However, the use of concept
maps in nursing education has been under-explored. OBJECTIVES: The aim of this
study was to explore how students develop concept maps and what these concept
maps consist of, and their views on the use of concept maps as a learning
activity in a PBL class. DESIGN: A qualitative approach consisting of an analysis
of the contents of the concept maps and interviews with students. SETTINGS: The
study was conducted in a school of nursing in a university in Hong Kong.
PARTICIPANTS: A total of 38 students who attended the morning session (20
students) and afternoon session (18 students) respectively of a nursing problem
based learning class. METHODS: The students in both the morning and afternoon
classes were allocated into four groups (4-5 students per group). Each group was
asked to draw two concept maps based on a given scenario, and then to participate
in a follow-up interview. Two raters individually assessed the concept maps, and
then discussed their views with each other. RESULTS: Among the concept maps that
were drawn, four were selected. Their four core features of those maps were: a)
the integration of informative and artistic elements; b) the delivery of
sensational messages; c) the use of images rather than words; and d) three
dimensional and movable. Both raters were concerned about how informative the
presentation was, the composition of the elements, and the ease of comprehension,
and appreciated the three-dimensional presentation and effective use of images.
From the results of the interview, the pros and cons of using concept maps were
discerned. CONCLUSIONS: This study demonstrated how concept maps could be
implemented in a PBL class to boost the students' creativity and to motivate them
to learn. This study suggests the use of concept maps as an initiative to
motivate student to learn, participate actively, and nurture their creativity. To
conclude, this study explored an alternative way for students to make
presentations and pioneered the use of art-based concept maps to facilitate
student learning.
PMID- 28414999
TI - Enhanced adsorption of bromate from aqueous solutions on ordered mesoporous Mg-Al
layered double hydroxides (LDHs).
AB - An ordered mesoporous Mg-Al layered double hydroxide (meso-LDH350) with a fairly
high Brunauer-Emmett-Teller (BET) surface area (126m2g-1) has been facilely
synthesized and then evaluated for the adsorptive removal of bromate from aqueous
solutions. Adsorbents were characterized by a variety of techniques (e.g., XRD,
FTIR, SEM, TG-DSC, N2 physisorption, XPS, etc.). The adsorption studies indicated
that the presence of background electrolytes and competitive anions can obviously
repress the uptake of bromate on LDHs. The adsorption isotherms agree well with
the Langmuir model, giving a maximum adsorption capacity of 59.34mgg-1 (pH 7.5,
10 degrees C) for meso-LDH350, which is much higher than other LDH-type
adsorbents reported in literature. The adsorption kinetic data can be well fitted
with the pseudo-second-order rate model. Based on the macroscopic and microscopic
studies, bromate adsorption on meso-LDH350 was associated with two mechanisms:
the reconstruction of the layered structures of meso-LDH350 and the anion
exchange between bromate and the intercalated anions.
PMID- 28415000
TI - Changes in copper toxicity towards diatom communities with experimental warming.
AB - Biological communities in aquatic environments most commonly face multiple
stress, where natural and anthropogenic stressors often act jointly. Their
interactions are most easily assessed using short cycle organisms such as
periphytic diatoms. In this experiment, we analyzed the combined effects of
copper exposure and warming on diatom successions over 6 weeks. Natural biofilm
collected in winter was left to grow in mesocosms exposed or unexposed to
realistic Cu concentrations at four different temperatures. Separate and joint
impacts of the two stressors were determined through structural and functional
endpoints. Both temperature and copper influenced the biological responses; their
interaction, when significant, was always antagonistic. Diatom communities
gradually changed with rising temperature. Under copper exposure, the dominant
Planothidium lanceolatum was superseded by Achnanthidium exiguum, which accounted
for about 70% relative abundance in the warmest conditions (18-23 degrees C).
Tolerance to copper was derived from dose-response curves based on photosynthesis
inhibition. Cu-induced community tolerance was always found, but it decreased
with warming and time. Biodiversity loss associated with lower Cu tolerance under
combined Cu exposure and increasing temperatures evidences the major influence of
cumulative stressors on aquatic health. These results highlight the crucial
interplay between environmental stressors, which are expected to intensify with
climate change.
PMID- 28415001
TI - Degradation of synthetic fragrances by laccase-mediated system.
AB - Laccase mediator systems are important biodegradation agents as the rate of
reaction could be enhanced in the presence of redox mediators. In the present
study the commercial enzyme laccase from Trametes versicolor and the redox
mediator 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) were used
for the biotransformation of the synthetic fragrances 1-(1,2,3,4,5,6,7,8
octahydro-2,3,8,8,-tetramethyl-2-naphthyl)ethan-1-one (Iso-E-Super, OTNE),
1,3,4,6,7,8,-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyran
(Galaxolide, HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtalene
(Tonalide, AHTN) and the transformation product of HHCB, 1,3,4,6,7,8-hexahydro
4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyran-1-one (Galaxolidone, HHCB
lactone) in water. A particular focus was to assess the effects of the enzyme
laccase from Trametes versicolor in the enantioselective degradation of the
target compounds, for this reason gas chromatography with an enantioselective
column was used as separation technique followed by mass spectrometry detection.
In addition, as enantioselective degradation of musk fragrances was observed in
wastewater, sewage sludge and fish samples, enantiomeric fractions of selected
compounds were studied during composting. In a period of 144h, the target
fragrances could be effectively removed by the enzyme laccase with removal
percentages greater than 70%, except AHTN with a removal percentage of 42%.
However, the degradation process prompted by the enzyme laccase was shown to be
non-enantioselective as no significant differences were observer between the
enantiomeric fractions calculated at the beginning and at the end of the
degradation process. Meanwhile, the composting process was shown to be
enantioselective.
PMID- 28415002
TI - Experimental and numerical study of liquefied natural gas (LNG) pool spreading
and vaporization on water.
AB - The investigation of pool spreading and vaporization phenomenon is an essential
part of consequence analysis to determine the severity of LNG spills on water. In
this study, release of LNG on water during marine operations is studied through
experimental and numerical methods The study involves emulation of an LNG leak
from transfer arms during side by side loading operations. The experimental part
involves flow of LNG in a narrow trench filled with water and subsequent
measurement of pool spreading and vaporization parameters. The numerical part
involves CFD simulation using a three dimensional hybrid homogenous Eulerian
multiphase solver to model the pool spreading and vaporization phenomenon. In
this method, LNG is modeled as dispersed phase droplets which can interact with
continuous phases - water and air through interphase models. The numerical study
also employs a novel user-defined routine for capturing the LNG vaporization
process. The CFD solver was capable of capturing the salient features of LNG pool
spreading and vaporization phenomena. It was observed from experiment and CFD
simulation that wind influenced both pool spreading and vaporization phenomenon
through entrainment and convection.
PMID- 28415003
TI - Less-favourable prognosis for low-risk endometrial cancer patients with a
discordant pre- versus post-operative risk stratification.
AB - BACKGROUND: Pre-operative risk stratification based on endometrial sampling
determines the extent of surgery for endometrial cancer (EC). We investigated the
concordance of pre- and post-operative risk stratifications and the impact of
discordance on survival. METHODS: Patients diagnosed with EC within the first 6
months of the years 2005-2014 were selected from the Netherlands Cancer Registry
(N = 7875). Pre- and post-operative risk stratifications were determined based on
grade and/or histological subtype for 3784 eligible patients. RESULTS: A
discordant risk stratification was found in 10% of patients: 4% (N = 155) had
high pre- and low post-operative risk and 6% (N = 215) had low pre- and high post
operative risk. Overall survival of patients with high pre- and low post
operative risk was less favourable compared to those with a concordant low risk
(80% versus 89%, p = 0.002). This difference remained significant when correcting
for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95%
confidence interval 1.28-2.53, p = 0.001). Survival of patients with low pre- and
high post-operative risk did not differ from those with a concordant high risk
(64% versus 62%, p = 0.295). CONCLUSION: Patients with high pre- and low post
operative risk have a less favourable prognosis compared to patients with a
concordant low risk. Pre-operative risk stratifications contain independent
prognostic information and should be incorporated into clinical decision-making.
PMID- 28415004
TI - Types of household humidifier disinfectant and associated risk of lung injury
(HDLI) in South Korea.
AB - From 2002 through 2015, hundreds of people died of fatal lung injuries associated
with the use of humidifier disinfectants (HDs) in Korea. Several chemical
disinfectants used for household humidifiers were later clinically confirmed to
cause HD-associated lung injury (HDLI). The aim of this study is to evaluate the
registered lung disease cases and to compare the distribution of HDLI patients,
including deaths, by HD use characteristics including types of HD and HD brands
categorized by age group. A total of 530 registered were clinically examined
through two rounds of investigations conducted from July 2013 until April 2015.
Information on HD use was obtained from a structured questionnaire and home
investigations. Approximately one-half of the patients (n=221) were clinically
confirmed to be associated with the use of HDs. Pregnant women (n=35, 16%) and
pre-school children<=6years old (n=128, 58%) accounted for most of the HD
associated lung injury patients (n=163, 74%). Sixty-seven percent of HDLI
patients developed HDLI after less than one year of HD use. HD products
containing polyhexamethylene guanidine phosphate (PHMG) were the most frequently
used among confirmed HDLI patients (n=123, 55.7%), followed by oligo (2-(2
ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and a mixture of
chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%).
Other HDs did not appear to be linked to HDLI. The majority of the HDLI patients
(n=85, 38.5%) was found to use only Oxy Saksak(r) products containing PHMG. The
development of HDLI was clinically found to be associated with the use of several
HD products containing PHMG and PGH, and to lesser extent, CMIT/MIT.
PMID- 28415005
TI - Agricultural sustainable intensification improved nitrogen use efficiency and
maintained high crop yield during 1980-2014 in Northern China.
AB - Global population increase will require rapid increase of food production from
existing agricultural land by 2050, which will inevitably mean the increase of
agricultural productivity. Due to agricultural sustainable intensification since
the 1990s, crop production in Huantai County of northern China has risen to 15tha
1yr-1 for the annual wheat-maize rotation system. We examined the temporal
dynamics of nitrogen (N) budget, N losses, and N use efficiency (NUE) during the
35years (1980-2014) in Huantai. The results revealed that atmospheric N
deposition increased 220% while reactive N losses decreased by 21.5% from 1980s
to 2010s. During 1980-2002, annual N partial factor productivity (PFPN), apparent
NUE and N recovery efficiency (REN) increased from 20.3 to 40.7kggrainkg-1Nfert,
from 36.5% to 71.0%, and from 32.4% to 57.7%, respectively; meanwhile, reactive N
losses intensity, land use intensity and N use intensity decreased by 69.8%,
53.4%, 50.0%, respectively, but without further significant changes after 2002.
Overall increases in NUE and decreases in N losses were largely due to the
introduction of optimized fertilization practice, mechanization and increased
incorporation of crop straw in Huantai. Straw incorporation was also significant
in soil N stock accrual and fertility improvement. By 2030, northern China may
reach the lowest end of PFPN values in developed countries (>45kggrainkg-1Nfert).
These agricultural sustainable intensification practices will be critical in
maintaining high grain yields and associated decreases in environmental
pollution, although water use efficiency in the region still needs to be
improved.
PMID- 28415006
TI - Accumulation of nonessential trace elements (Ag, As, Cd, Cr, Hg and Pb) in
Atlantic horseshoe crab (Limulus polyphemus) early life stages.
AB - During early development, benthic organisms can accumulate nonessential trace
elements through aqueous and particulate sources. This study investigated the
accumulation of Ag, As, Cd, Cr, Hg and Pb in Atlantic horseshoe crab (Limulus
polyphemus) pre-spawned eggs, embryos, and developing larvae collected from 5
sites on Long Island, NY and compared these concentrations to that found in
sediment, pore water, and overlying water. All investigated elements were
detected in embryos and larvae at all sites. Arsenic was found at the highest
concentration in each life stage across all 5 sites, followed by Ag, whereas Cd,
Hg and Pb concentrations varied between sites. Chromium was not detected in pre
spawned eggs, but was present in embryos and larvae at all sites, however, along
with Hg, significantly increased from embryo to larvae at most sites. We conclude
that observed accumulation patterns are likely a result of abiotic factors,
differences in uptake pathways between life stages and the rate of excretion.
Future laboratory studies are required to understand the factors influencing the
aqueous and dietary uptake of nonessential trace elements in the early life
stages of Atlantic horseshoe crabs.
PMID- 28415007
TI - Religion, spirituality, and mental health of U.S. military veterans: Results from
the National Health and Resilience in Veterans Study.
AB - BACKGROUND: In the last three decades, there has been increased interest in
studying the association between religion/spirituality (R/S), and mental health
and functional outcomes. METHODS: Using data from a contemporary, nationally
representative sample of 3151 U.S. military veterans maintained by GfK Knowledge
Networks, Inc., we evaluated the relation between R/S and a broad range of mental
health, and psychosocial variables. Veterans were grouped into three groups based
on scores on the Duke University Religion Index: High R/S (weighted 11.6%),
Moderate R/S (79.7%) and Low R/S (8.7%). RESULTS: A "dose-response" protective
association between R/S groups and several mental health outcomes was revealed,
even after adjustment for sociodemographic and military variables. High R/S was
associated with decreased risk for lifetime posttraumatic stress disorder (odds
ratio [OR]=0.46), major depressive disorder (MDD; OR=0.50), and alcohol use
disorder (OR=0.66), while Moderate R/S was associated with decreased risk for
lifetime MDD (OR=0.66), current suicidal ideation (OR=0.63), and alcohol use
disorder (OR=0.76). Higher levels of R/S were also strongly linked with increased
dispositional gratitude, purpose in life, and posttraumatic growth. LIMITATIONS:
In this cross-sectional study, no conclusions regarding causality can be made.
The study provides a current snapshot of the link between R/S and mental health.
The study also cannot determine whether religious coping styles (negative vs
positive coping) contributed to observed differences. CONCLUSIONS: Although the
present study does not have treatment implications, our results suggest that
higher levels of R/S may help buffer risk for certain mental disorders and
promote protective psychosocial characteristics in U.S. military veterans.
PMID- 28415008
TI - Bipolar mood state reflected in cortico-amygdala resting state connectivity: A
cohort and longitudinal study.
AB - BACKGROUND: Using resting-state functional magnetic resonance imaging (rsfMRI),
we previously compared cohorts of bipolar I subjects in a manic state to those in
a euthymic state to identify mood state-specific patterns of cortico-amygdala
connectivity. Our results suggested that mania is reflected in the disruption of
emotion regulation circuits. We sought to replicate this finding in a group of
subjects with bipolar disorder imaged longitudinally across states of mania and
euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged
in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged
longitudinally across both mood states. We measured differences in amygdala
connectivity between the mania and euthymia cohorts. We then used these regions
of altered connectivity to examine connectivity in the longitudinal bipolar group
using a within-subjects design. RESULTS: Our findings in the mania vs euthymia
cohort comparison were replicated in the longitudinal analysis. Bipolar mania was
differentiated from euthymia by decreased connectivity between the amygdala and
pre-genual anterior cingulate cortex. Mania was also characterized by increased
connectivity between amygdala and the supplemental motor area, a region normally
anti-correlated to the amygdala in emotion regulation tasks. LIMITATIONS:
Stringent controls for movement effects limited the number of subjects in the
longitudinal sample. CONCLUSIONS: In this first report of rsfMRI conducted
longitudinally across mood states, we find that previously observed between-group
differences in amygdala connectivity are also found longitudinally within
subjects. These results suggest resting state cortico-amygdala connectivity is a
biomarker of mood state in bipolar disorder.
PMID- 28415009
TI - Selective HDAC inhibitors with potent oral activity against leukemia and
colorectal cancer: Design, structure-activity relationship and anti-tumor
activity study.
AB - Previously, we reported the discovery of a series of N-hydroxycinnamamide-based
HDAC inhibitors, among which compound 11y exhibited high HDAC1/3 selectivity. In
this current study, structural derivatization of 11y led to a new series of
benzamide based HDAC inhibitors. Most of the compounds exhibited high HDACs
inhibitory potency. Compound 11a (with 4-methoxybenzoyl as N-substituent in the
cap and 4-(aminomethyl) benzoyl as the linker group) exhibited selectivity
against HDAC1 to some extent, and showed potent antiproliferative activity
against several tumor cell lines. In vivo studies revealed that compound 11a
displayed potent oral antitumor activity in both hematological tumor cell U937
xenograft model and solid tumor cell HCT116 xenograft model with no obvious
toxicity. Further modification of benzamide 3, 11a and 19 afforded new thienyl
and phenyl compounds (50a, 50b, 63a, 63b and 63c) with dramatic HDAC1 and HDAC2
dual selectivity, and the fluorine containing compound 56, with moderate HDAC3
selectivity.
PMID- 28415010
TI - Structure and biological properties of mixed-ligand Cu(II) Schiff base complexes
as potential anticancer agents.
AB - We synthesized two mixed-ligand Cu(II) complexes containing different
aroylhydrazone ligands and a pyridine co-ligand, namely, [Cu(L1)(Py)] (C1) and
[Cu(L2)(Py)(Br)] (C2) (L1 = (E)-2-hydroxy-N'-((2-hydroxynaphthalen-1
yl)methylene)benzohydrazide, Py = pyridine, L2 = (E)-2-hydroxy-N'-(phenyl(pyridin
2-yl)methylene)benzohydrazide), and assessed their chemical and biological
properties to understand their marked activity. C2 showed better anticancer
activity than C1 in various human cancer cell lines, including the cisplatin
resistant lung cancer cell line A549cisR. Both Cu(II) complexes, especially C2,
displayed promising anti-metastatic activity against HepG2 cells. Spectroscopic
titration and agarose gel electrophoresis experiments indicated that C2 exhibited
binding affinity toward calf-thymus DNA and efficient pBR322 DNA-cleaving
ability. Further mechanistic studies showed that C2 effectively induced DNA
damage and thus led to cell cycle arrest at the G2/M phase, and also stimulated
mitochondrial dysfunction mediated by reactive oxygen species and caspase
dependent apoptosis.
PMID- 28415011
TI - Design and synthesis of novel xanthine derivatives as potent and selective A2B
adenosine receptor antagonists for the treatment of chronic inflammatory airway
diseases.
AB - Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics
through activation of A2B adenosine receptor (A2BAdoR). Selective antagonists
have been shown to attenuate airway reactivity and improve inflammatory
conditions in pre-clinical studies. Hence, the identification of novel, potent
and selective A2BAdoR antagonist may be beneficial for the potential treatment of
asthma and Chronic Obstructive Pulmonary Disease (COPD). Towards this effort, we
explored several prop-2-ynylated C8-aryl or heteroaryl substitutions on xanthine
chemotype and found that 1-prop-2-ynyl-1H-pyrazol-4-yl moiety was better
tolerated at the C8 position. Compound 59, exhibited binding affinity (Ki) of 62
nM but was non-selective for A2BAdoR over other AdoRs. Incorporation of
substituted phenyl on the terminal acetylene increased the binding affinity (Ki)
significantly to <10 nM. Various substitutions on terminal phenyl group and
different alkyl substitutions on N-1 and N-3 were explored to improve the
potency, selectivity for A2BAdoR and the solubility. In general, compounds with
meta-substituted phenyl provided better selectivity for A2BAdoR compared to that
of para-substituted analogs. Substitutions such as basic amines like pyrrolidine,
piperidine, piperazine or cycloalkyls with polar group were tried on terminal
acetylene, keeping in mind the poor solubility of xanthine analogs in general.
However, these substitutions led to a decrease in affinity compared to compound
59. Subsequent SAR optimization resulted in identification of compound 46 with
high human A2BAdoR affinity (Ki = 13 nM), selectivity against other AdoR subtypes
and with good pharmacokinetic properties. It was found to be a potent functional
A2BAdoR antagonist with a Ki of 8 nM in cAMP assay in hA2B-HEK293 cells and an
IC50 of 107 nM in IL6 assay in NIH-3T3 cells. Docking study was performed to
rationalize the observed affinity data. Structure-activity relationship (SAR)
studies also led to identification of compound 36 as a potent A2BAdoR antagonist
with Ki of 1.8 nM in cAMP assay and good aqueous solubility of 529 MUM at neutral
pH. Compound 46 was further tested for in vivo efficacy and found to be
efficacious in ovalbumin-induced allergic asthma model in mice.
PMID- 28415012
TI - Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives
as new potent and selective human sirtuin 2 inhibitors.
AB - Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such
as cell cycle regulation, autophagy, immune and inflammatory responses.
Dysregulation of SIRT2 was considered as a main aspect contributing to several
human diseases, including cancer. Development of new potent and selective SIRT2
inhibitors is currently desirable, which may provide a new strategy for treatment
of related diseases. Herein, a structure-based optimization approach led to new 2
((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives as SIRT2
inhibitors. SAR analyses with new synthesized derivatives revealed a number of
new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an
IC50 value of 42 nM. The selectivity analyses found that 28e has a very good
selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a
potent ability to inhibit human breast cancer cell line MCF-7 and increase the
acetylation of alpha-tubulin in a dose-dependent manner. This study will aid
further efforts to develop highly potent and selective SIRT2 inhibitors for the
treatment of cancer and other related diseases.
PMID- 28415013
TI - The effect of exercise on fatigue and physical functioning in breast cancer
patients during and after treatment and at 6 months follow-up: A meta-analysis.
AB - Breast cancer is the leading cause of cancer in women worldwide. Exercise
interventions may improve physical and psychological factors during and after
active breast cancer treatment. The aim of this systematic review was to assess
the current knowledge regarding the efficacy of physical exercise with respect to
fatigue and self-reported physical functioning. Systematic searches in Cochrane
Library, Medline, Embase, Cinahl, PsycINFO, AMED and PEDro. After assessing the
quality of the studies, we identified 25 randomized controlled trials that
included 3418 breast cancer patients. An increase in physical functioning and a
decrease in fatigue were observed after a physical exercise intervention, with an
SMD of 0.27 (0.12, 0.41) and -0.32 (-0.49, - 0.14), respectively. There were
slightly higher improvements in physical functioning and fatigue when the
patients received the intervention after adjuvant breast cancer treatment. The 6
month follow-up data showed a small favourable difference for the physical
exercise group for both physical functioning and fatigue. This systematic review
found that an exercise intervention program can produce short-term improvements
in physical functioning and can reduce fatigue in breast cancer patients.
However, more studies are needed to confirm the time-dependent observations in
this study.
PMID- 28415014
TI - Determination and quantification of intracellular fludarabine triphosphate,
cladribine triphosphate and clofarabine triphosphate by LC-MS/MS in human cancer
cells.
AB - Purine nucleoside analogues are widely used in the treatment of haematological
malignancies, and their biological activity is dependent on the intracellular
accumulation of their triphosphorylated metabolites. In this context, we
developed and validated a liquid chromatography tandem mass spectrometry (LC
MS/MS) method to study the formation of 5'-triphosphorylated derivatives of
cladribine, fludarabine, clofarabine and 2'-deoxyadenosine in human cancer cells.
Br-ATP was used as internal standard. Separation was achieved on a hypercarb
column. Analytes were eluted with a mixture of hexylamine (5 mM), DEA (0.4%, v/v,
pH 10.5) and acetonitrile, in a gradient mode at a flow rate of 0.3mLmin-1.
Multiple reactions monitoring (MRM) and electrospray ionization in negative mode
(ESI-) were used for detection. The application of this method to the
quantification of these phosphorylated cytotoxic compounds in a human follicular
lymphoma cell line, showed that it was suitable for the study of relevant
biological samples.
PMID- 28415016
TI - An LC-MS/MS method for the determination of antibiotic residues in distillers
grains.
AB - Antibiotics are used in ethanol production to discourage the growth of bacteria
that would result in lower ethanol content and a lower quality product. A survey
conducted by the FDA (FY 2010 Nationwide Survey of Distillers Grains for
Antibiotic Residues, 2009 [1]) revealed that the residues of these antibiotics
can remain in the distillers grains (DG) by-product, which is used as an animal
feed ingredient. The low levels of antibiotic residues in DG could be a public
health concern, as they could lead to antimicrobial resistance. To enable the
quantitative determination of these antibiotics (erythromycin, penicillin G,
virginiamycin M1 and virginiamycin S1), we developed a sensitive LC-MS/MS method.
The residues were extracted from distillers grains with a mixture of acetonitrile
and buffer followed by acetonitrile. The combined extract was diluted with water
and washed with hexane. An aliquot was cleaned up on an Oasis HLB solid phase
extraction cartridge. Extracts were analyzed by LC-tandem mass spectrometry. The
method was successfully validated using a variety of different matrices such as
corn DG, corn & milo DG, and deoiled corn DG. Absolute recoveries of the analytes
ranged from 53 to 106%. Accuracy ranged from 90 to 101% based on calibration by
matrix standards. The limits of quantitation and relative standard deviation were
all satisfactory to support future surveillance studies.
PMID- 28415015
TI - Lipidomics by ultrahigh performance liquid chromatography-high resolution mass
spectrometry and its application to complex biological samples.
AB - An improved approach for selective and sensitive identification and quantitation
of lipid molecular species using reversed phase chromatography coupled to high
resolution mass spectrometry was developed. The method is applicable to a wide
variety of biological matrices using a simple liquid-liquid extraction procedure.
Together, this approach combines multiple selectivity criteria: Reversed phase
chromatography separates lipids according to their acyl chain length and degree
of unsaturation and is capable of resolving positional isomers of
lysophospholipids, as well as structural isomers of diacyl phospholipids and
glycerolipids. Orbitrap mass spectrometry delivers the elemental composition of
both positive and negative ions with high mass accuracy. Finally, automatically
generated tandem mass spectra provide structural insight into numerous
glycerolipids, phospholipids, and sphingolipids within a single run. Calibration
showed linearity ranges of more than four orders of magnitude, good values for
accuracy and precision at biologically relevant concentration levels, and limits
of quantitation of a few femtomoles on column. Hundreds of lipid molecular
species were detected and quantified in three different biological matrices,
which cover well the wide variety and complexity of various model organisms in
lipidomic research. Together with a software package, this method is a prime
choice for global lipidomic analysis of even the most complex biological samples.
PMID- 28415017
TI - Accelerated solvent extraction method for the quantification of polycyclic
aromatic hydrocarbons in cocoa beans by gas chromatography-mass spectrometry.
AB - An accelerated solvent extraction (ASE) procedure for use with gas chromatography
mass spectrometry (GC-MS) was optimized for the determination of eight polycyclic
aromatic hydrocarbons (PAHs) in cocoa beans. Plackett-Burman and rotatable
central composite design (RCCD) indicated that three variables affected the
recoveries of PAHs during the extraction and purification steps: agitation time
in the second liquid-liquid partition, weight of silica gel in the column, and
volume of hexane for PAH elution from the column. After obtaining the optimal
conditions, a single laboratory method validation was performed. Linearity was
demonstrated for benzo[a]pyrene in the concentration range from 0.5 to 8.0mgkg-1
of sample, corresponding to 1.25-20.0MUgkg-1 of cocoa on a fat basis. For the
other analytes, linearity was observed from 0.75 to 8.0MUgkg-1 of sample (1.88
20.0MUgkg-1 of cocoa on a fat basis). Significant matrix effects were found for
chrysene and benzo[b]fluoranthene. The precision of the method was verified with
relative standard deviations (RSDs) ranging from 2.57 to 14.13% and from 4.36 to
19.77% under repeatability and intermediate precision conditions, respectively.
The average recoveries of the eight PAHs ranged from 74.99 to 109.73%. These
parameters, limits and measurement uncertainties met the performance criteria
established by European Union regulations, except for the theoretical limit of
detection for chrysene. The method was applied to the analysis of samples of
Brazilian cocoa beans, and only one sample was found to have a PAH content above
the maximum limit defined by the European Union legislation. This optimized and
validated method is intended to be used as part of the official Brazilian
monitoring programs investigating contaminants and residues in food.
PMID- 28415018
TI - Internal consistency and concurrent validity of the Montreal Cognitive Assessment
in individuals with major depressive disorder.
AB - This study aimed to determine the internal consistency and concurrent validity of
the Montreal Cognitive Assessment (MoCA), as well as its subtests, in patients
with major depressive disorder (MDD). Participants were patients with DSM-IV MDD
aged between 21 and 65 years. Neurocognitive function was assessed by using the
MoCA and 12 neurocognitive tests. The composite z-score of 12 neurocognitive
tests, which indicated the global cognitive performance, was calculated.
Participants were 57 outpatients with MDD. Except the MoCA Orientation, each of
the MoCA subtests showed a wide range of scores. The average inter-item
correlation and the Cronbach's alpha of MoCA were 0.24 and 0.64, respectively.
The MoCA total score was significantly and highly associated with the composite z
score of 12 neurocognitive tests (Pearson's r=0.78, p<0.001). The score of each
MoCA subtest was significantly and moderately correlated with the z-score of its
analogous neuropsychological test (absolute Spearman's rs's=0.33-0.56,
p's<=0.01). The MoCA and its subtests are reliable and valid for assessing global
and specific cognitive performance in patients with MDD and could be a tool for
screening neurocognitive deficits in depressed patients.
PMID- 28415019
TI - Recovery of infective virus particles in ion-exchange and hydrophobic interaction
monolith chromatography is influenced by particle charge and total-to-infective
particle ratio.
AB - Viral particles are used in medical applications as vaccines or gene therapy
vectors. In order to obtain product of high purity, potency and safety for
medical use purification of virus particles is a prerequisite, and chromatography
is gaining increased attention to meet this aim. Here, we report on the use of
ion-exchange and hydrophobic interaction chromatography on monolithic columns for
purification of mumps virus (MuV) and measles virus (MeV). Efficiency of the
process was monitored by quantification of infective virus particles (by 50% cell
culture infective dose assay) and total virus particles, and monitoring of their
size (by Nanoparticle Tracking Analysis). Ion-exchange chromatography was shown
to be inefficient for MuV and best results for MeV were obtained on QA column
with recovery around 17%. Purification of MuV and MeV by hydrophobic interaction
chromatography resulted in recoveries around 60%. Results showed that columns
with small channels (d=1.4MUm) are not suitable for MuV and MeV, although their
size is below 400nm, whereas columns with large channels (6MUm) showed to be
efficient and recoveries independent on the flow rate up to 10mL/min.
Heterogeneity of the virus suspension and its interday variability mostly
regarding total-to-infective particle ratio was observed. Interestingly, a trend
in recovery depending on the day of the harvest was also observed for both
viruses, and it correlated with the total-to-infective particle ratio, indicating
influence of the virus sample composition on the chromatography results.
PMID- 28415020
TI - Simultaneous determination of ten bioactive constituents of Sanjie Zhentong
Capsule in rat plasma by ultra-high-performance liquid chromatography tandem mass
spectrometry and its application to a pharmacokinetic study.
AB - Sanjie Zhentong capsule, a well-known traditional Chinese medicine prescription,
are used for the treatment of endometriosis-related diseases. In this study, a
simple, rapid and sensitive ultra-high-performance liquid chromatography-tandem
mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous
determination of ten bioactive constituents, including peimine, peiminine,
peimisine, loureirin A, loureirin B, 7,4'-dihydroxyflavone, pterostilbene,
ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 in rat plasma after oral
administration of Sanjie Zhentong capsule. The sample preparations for protein
removal was accomplished using a simple methanol precipitation method. The
analytes were completely separated from the endogenous compounds on an Agilent
Poroshell 120 SB-C18 column (4.6mm*150mm, 2.7MUm) using an isocratic elution with
methanol - 0.1% formic acid aqueous (4/1, v/v) as a mobile phase. The single-run
analysis time was as short as 14.0min. The inter-day and intra-day precision of
the quality control samples exhibited relative standard deviations (RSD) <9.5%
and the accuracy values ranged from -8.6% to 15.0%. The lower limits of
quantification (LLOQ) were 10, 10, 10, 10, 10, 10, 5, 10, 10 and 20ng/mL for
peimine, peiminine, peimisine, loureirin A, loureirin B, 7,4'-dihydroxyflavone,
pterostilbene, ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1,
respectively. The analytical method was successfully applied to a pharmacokinetic
study of the multi-components after oral administration of Sanjie Zhentong
Capsule in rats.
PMID- 28415021
TI - In vitro Investigation of Metabolic Profiling of a Potent Topoisomerase
Inhibitors Fluorescein Hydrazones (FLHs) in RLMs by LC-MS/MS.
AB - Metabolic profiling of newly reported two topoisomerase inhibitors namely
fluorescein hydrazones (FLHs) were studied in rat liver microsomes (RLMs) and the
data were acquired in a liquid chromatography (LC) ion trap mass spectrometry.
(E)-3',6'-dihydroxy-2-((2-nitrobenzylidene)amino)spiro[isoindoline-1,9'-xanthen]
3-one (1) was bio-transformed into two mono-hydroxylated, one double hydroxylated
and a tetra hydroxylated metabolites, on the other hand, (Z)-3',6'-dihydroxy-2
((2-oxoindolin-3-ylidene)amino)spiro[isoindoline-1,9'-xanthen]-3-one (2) was bio
transformed into eight possible metabolites by cleavage reduction, hydroxylation,
cleavage reduction together with hydroxylated and azo-reduction in RLMs in
presence of NADPH-generating system. No metabolites were generated in the absence
of either NADPH or microsomes for the compounds (1 and 2), indicating a likely
involvement of CYP450 enzymes and the cofactor NADPH in the metabolisms. The
structures of those metabolite were elucidated by MS/MS fragmentation study.
PMID- 28415022
TI - Simultaneous determination of tryptophan and 8 metabolites in human plasma by
liquid chromatography/tandem mass spectrometry.
AB - Tryptophan (Trp) is an essential amino-acid and the precursor of many
biologically active substances such as kynurenine (KYN) and serotonin (5HT). Its
metabolism is involved in different physiopathological states, such as
cardiovascular diseases, cancer, immunomodulation or depression. Hence, the
quantification of Trp catabolites, from both KYN and 5HT pathways, might be
usefulfor the discovery of novel diagnostic and follow-up biomarkers. We have
developed a simple method for quantification of Trp and 8 of its
metabolites,involved in both KYN and 5HT pathways, using liquid chromatography
coupled to tandem mass spectrometry. We also validated the methodin human plasma
samples, according to NF EN ISO 15189 criteria. Our method shows acceptable intra
and inter-day coefficients of variation (CV) (<12% and <16% respectively). The
linearity entirelycovers the human plasma range. Stabilities of whole blood and
of residues weredetermined, as well as the use of 2 different types of
collectiontube, enabling us to adapt our process. Matrix effects and reference
values showed good agreement compared to the literature. We propose here a method
allowing the simultaneous quantification of a panel of Trp catabolites, never
used before to our knowledge. This method, witha quickchromatographic runtime
(15min) and simple sample preparation, has beenvalidated according to NF EN ISO
15189 criteria. The method enables the detailed analysis of these metabolic
pathways, which are thought to be involved in a number of pathological
conditions.
PMID- 28415023
TI - Drosophila models of prionopathies: insight into prion protein function,
transmission, and neurotoxicity.
AB - Prion diseases (PrD) are unique neurodegenerative conditions with sporadic,
genetic, and infectious etiologies. The agent responsible for these pathologies
is a misfolded conformation of the prion protein (PrP). Although a process of
autocatalytic "conversion" is known to mediate disease transmission, important
gaps still remain regarding the physiological function of PrP and its relevance
to pathogenesis, the molecular and cellular mechanisms mediating neurotoxicity
and transmission, and the PrP conformations responsible for neurotoxicity. New
Drosophila models expressing mammalian PrP have revealed physiological insight
into PrP function and opened the door to significant progress in prion
transmission and PrP neurotoxicity. Importantly, flies expressing human PrP
showing a robust eye phenotype will allow performing genetic screens to uncover
novel mechanisms mediating PrP neurotoxicity.
PMID- 28415024
TI - Glucocorticoids differentially regulate the innate immune responses of TLR4 and
the cytosolic DNA sensing pathway.
AB - Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders
because of their powerful anti-inflammatory properties; however, their effects on
macrophage-mediated immune responses are not completely understood. In the
present study, we found that GCs decreased LPS-mediated TBK1 activation and the
expression of IFN-beta, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1
activity and cytokine expression were not affected by GCs treatment. Furthermore,
GCs decreased the expression of key autophagy-related genes (ATGs), including
ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS
stimulation. However, GCs had no effect on poly(dA:dT)-mediated autophagy and ATG
expression in macrophages. Collectively, this study demonstrates that GCs inhibit
the TLR4-mediated innate immune response, but do not affect the cytosolic DNA
sensing pathway. This provides new insights into the immunomodulatory mechanisms
of GCs in macrophages, which may provide useful information for the clinical use
of GCs in treating chronic inflammatory disorders.
PMID- 28415025
TI - Unusual combination of femoral head dislocation associated acetabular fracture
with multipart femoral fractures: Case report.
AB - INTRODUCTION: Traumatic hip dislocation associated with femur intertrocanteric
fracture is a rare and severe injury and it frequently occurs following a high
energy trauma, Associated acetabular fractures with this injury are even more
rare and potentially cause devastating consequences including avascular necrosis
of the femoral head and subsequent early secondary osteoarthritis of the hip
joint. PRESENTATION OF CASE: In this case report, we present a 20year old
polytraumatized patient with traumatic hip dislocation associated with
ipsilateral acetabulum fracture and simultaneous fractures of the ipsilateral
femur. DISCUSSION: Traumatic hip dislocation associated with femur
intertrochanteric fracture is a rare and severe injury and it frequently occurs
following a high energy trauma. In polytraumatized patients, musculoskeletal
injuries are the most common lesions requiring surgical intervention frequently
presenting challenging scenarios in terms of functional outcome and quality of
life. Osteonecrosis of the femoral head is a serious and unpredictable
complication that may occur after displaced femoral neck fracture and traumatic
hip dislocation due to the disturbed blood supply of the femoral head.
CONCLUSION: A staged treatment strategy may be useful managing an unstable
polytraumatized patient or a patient who requires prolonged transfer to receive
definitive care.
PMID- 28415026
TI - Effects of carbon nanotubes on phosphorus adsorption behaviors on aquatic
sediments.
AB - Aquatic sediments are believed to be an important sink for carbon nanotubes
(CNTs). With novel properties, CNTs can potentially disturb the fate and mobility
of the co-existing contaminants in the sediments. Only toxic pollutants have been
investigated previously, and to the best of our knowledge, no data has been
published on how CNTs influence phosphorus (P) adsorption on aquatic sediments.
In this study, multi-walled carbon nanotubes (MWCNTs) were selected as model
CNTs. Experimental results indicated that compared to pseudo-first order and
intraparticle diffusion models, the pseudo-second-order model is better for
describing the adsorption kinetics of sediments and MWCNT-contaminated sediments.
Adsorption isotherm studies suggested that the Langmuir model fits the isotherm
data well. With the increase in the MWCNT-to-sediment ratio from 0.0% to 5.0%,
the theoretical maximum monolayer adsorption capacity (Qmax) for P increased from
0.664 to 0.996mg/g. However, the Langmuir isotherm coefficient (KL) significantly
decreased from 4.231L/mg to 2.874L/mg, indicating the decrease in the adsorption
free energy of P adsorbed on the sediments after MWCNT contamination. It was
suggested that P was released more easily to the overlying water after the re
suspension of sediments. Moreover, the adsorption of sediments and sediment-MWCNT
mixture was endothermic and physical in nature. Results obtained herein suggested
that the change in the specific surface area and zeta potential of sediments is
related to MWCNT contamination, and the large adsorption capacity of MWCNTs is
probably the main factor responsible for the variation in the adsorption of P on
aquatic sediments.
PMID- 28415027
TI - The influence of sex on mock jurors' verdicts across type of child abuse cases.
AB - This study examined the influence of victim sex, mock juror sex, and type of
child abuse (physical, sexual, emotional, and neglect) on mock jurors'
assessments of eyewitness and defendant integrity, continuous guilt ratings,
dichotomous verdicts, and sentencing recommendations. Participants read one of
eight versions of a trial transcript and then answered a self-report
questionnaire. Female mock jurors were significantly more likely to find the
defendant guilty overall. Moreover, female mock jurors recommended significantly
longer sentences for defendants in sexual abuse cases; whereas, male mock jurors
recommended significantly longer sentences for defendants in sexual and physical
abuse cases. Male mock jurors perceived the defendant more favorably than female
mock jurors; whereas, female mock jurors perceived the alleged victim more
favorable than male mock jurors. These results suggest that juror sex may be an
influential factor in child abuse cases overall.
PMID- 28415028
TI - The dynamics of multimer formation of the amphiphilic hydrophobin protein HFBII.
AB - Hydrophobins are surface-active proteins produced by filamentous fungi. They have
amphiphilic structures and form multimers in aqueous solution to shield their
hydrophobic regions. The proteins rearrange at interfaces and self-assemble into
films that can show a very high degree of structural order. Little is known on
dynamics of multimer interactions in solution and how this is affected by other
components. In this work we examine the multimer dynamics by stopped-flow
fluorescence measurements and Forster Resonance Energy Transfer (FRET) using the
class II hydrophobin HFBII. The half-life of exchange in the multimer state was
0.9s at 22 degrees C with an activation energy of 92kJ/mol. The multimer exchange
process of HFBII was shown to be significantly affected by the closely related
HFBI hydrophobin, lowering both activation energy and half-life for exchange.
Lower molecular weight surfactants interacted in very selective ways, but other
surface active proteins did not influence the rates of exchange. The results
indicate that the multimer formation is driven by specific molecular interactions
that distinguish different hydrophobins from each other.
PMID- 28415029
TI - Multifunctional nanoparticles self-assembled from polyethylenimine-based graft
polymers as efficient anticancer drug delivery.
AB - Multiple functionalization of nanoparticles has attracted great interest in drug
delivery. In this paper, polymeric amphiphiles of polyethylenimine (PEI)
conjugated with methoxy poly(ethylene glycol) aldehyde (mPEG-CHO), poly(epsilon
caprolactone) aldehyde (PCL-CHO) and pyrene-1-carboxaldehyde (Py-CHO) were
synthesized via Schiff's reaction. The conjugates self-assembled into
nanoparticles with pH-sensitivity to load anticancer drug doxorubicin (DOX),
further coated with hyaluronic acid (HA) for tumor targeting. The mean size of
nanoparticles was about 100nm and the stability of the nanoparticles was well in
aqueous solution. The nanoparticles coated with HA showed faster disassembly in
acidic solution, resulting in faster drug release in the medium with pH 5.0
compared to uncoated nanoparticles. Moreover, the nanoparticles exhibited an
endosomal escape function to accelerate the release of DOX in cancer cells, which
led to low IC50s to kill breast cancer cells (4T1) and liver cancer cells (HepG2)
in vitro.
PMID- 28415030
TI - Contradictory roles of Nrf2/Keap1 signaling pathway in cancer
prevention/promotion and chemoresistance.
AB - NF-E2-related factor 2 (Nrf2) protein is a cytosolic transcription factor that
regulates antioxidant and stress-related enzymes. Kelch-like ECH-associated
protein 1 (Keap1) binds Nrf2 and accelerates ubiquitination and proteasome
dependent degradation of Nrf2. Nrf2 modifies the sensitivity of the cell
environment to electrophiles and oxidants by inducing the transcriptional
activation of more than 100 detoxification and cytoprotective genes. Prior
investigations have found documentary evidence indicating that temporary
activation of Nrf2 by pharmaceutical inducers plays a protective role against
cancer initiation in normal cells. The impact of Nrf2/Keap1 pathway in
development of tumorigenesis and drug resistance has also been well documented.
Inhibition of the permanent Nrf2 activation, especially in combination with
chemotherapeutics against cancer, may be considered as an important strategy to
inhibit tumor growth and overcome chemoresistance. Here, we review the importance
of Nrf2-keap1 pathway in the prevention or promotion of cancer, and resistance
mechanisms to chemotherapeutic agents.
PMID- 28415031
TI - Carotenoid accumulation in durian (Durio zibethinus) fruit is affected by
ethylene via modulation of carotenoid pathway gene expression.
AB - Carotenoid content in durian (Durio zibethinus) fruit is an important aspect of
fruit quality, with different cultivars distinguished by differing pigmentation.
We have studied the dependence of carotenogenesis on ethylene. Fruit of the
cultivar 'Chanee' harvested at the mature stage were either left untreated
(controls), treated with 1-methylcyclopropene (1-MCP) for 12 h, or treated with
application of an aqueous ethephon solution to the stem end, or treated for 12 h
with 1-MCP followed by ethephon application. Fruit were then stored for 9 d at 25
degrees C. Pulp color of durian became steadily yellowish as a result of
accumulation of carotenoids, which were mainly beta-carotene, and alpha-carotene,
with a minor amount of zeaxanthin and lutein. 1-MCP delayed the increase in the
accumulation of beta-carotene, alpha-carotene, and zeaxanthin, but not lutein. In
contrast, ethephon had no significant effect on carotenoid accumulation. The
expression of zeta-carotene desaturase (ZDS), lycopene beta-cyclase (LCYB),
chromoplast specific lycopene beta-cyclase (CYCB) and beta-carotene hydroxylase
(BCH) genes was highly correlated with carotenoid content and pulp color.1-MCP
resulted in significant down-regulation of ZDS, LCYB, CYCB and BCH expression.
The accumulation of beta-carotene and alpha-carotene appears to be controlled by
the level of expression of LCYB gene, whose function was tested in bacteria to
show conversion of lycopene and delta-carotene to beta-carotene and alpha
carotene, respectively. These results suggest that ripening-induced carotenoid
accumulation is regulated by endogenous ethylene controlling the expression of
key genes such as LCYB.
PMID- 28415032
TI - Comparative metabolome analysis of wheat embryo and endosperm reveals the dynamic
changes of metabolites during seed germination.
AB - In this study, we performed the first comparative metabolomic analysis of the
wheat embryo and endosperm during seed germination using GC-MS/MS. In total, 82
metabolites were identified in the embryo and endosperm. Principal component
analysis (PCA), metabolite-metabolite correlation and hierarchical cluster
analysis (HCA) revealed distinct dynamic changes in metabolites between the
embryo and endosperm during seed germination. Generally, the metabolite changes
in the embryo were much greater than those in the endosperm, suggesting that the
embryo is more active than the endosperm during seed germination. Most amino
acids were upregulated in both embryo and endosperm, while polysaccharides and
organic acids associated with sugars were mainly downregulated in the embryo.
Most of the sugars showed an upregulated trend in the endosperm, but significant
changes in lipids occurred only in the embryo. Our results suggest that the
embryo mobilises mainly protein and lipid metabolism, while the endosperm
mobilises storage starch and minor protein metabolism during seed germination.
The primary energy was generated mainly in the embryo by glycolysis during seed
imbibition. The embryo containing most of the genetic information showed
increased nucleotides during seed germination process, indicating more active
transcription and translation metabolisms.
PMID- 28415033
TI - Physiological investigation of C4-phosphoenolpyruvate-carboxylase-introduced rice
line shows that sucrose metabolism is involved in the improved drought tolerance.
AB - We compared the drought tolerance of wild-type (WT) and transgenic rice plants
(PC) over-expressing the maize C4PEPC gene, which encodes phosphoenolpyruvate
carboxylase (PEPC, EC 4.1.1.31) gene, and evaluated the roles of saccharide and
sugar-related enzymes in the drought response. Pot-grown seedlings were subjected
to real drought conditions outdoors, and the yield components were compared
between PC and untransformed wild-type (WT) plants. The stable yield from PC
plants was associated with higher net photosynthetic rate under the real drought
treatment. The physiological characters of WT and PC seedlings under a simulated
drought treatment (25% (w/v) polyethylene glycol-6000 for 3 h; PEG 6000
treatment) were analyzed in detail for the early response of drought. The
relative water content was higher in PC than in WT, and PEPC activity and the C4
PEPC transcript level in PC were elevated under the simulated drought conditions.
The endogenous saccharide responses also differed between PC and WT under
simulated drought stress. The higher sugar decomposition rate in PC than in WT
under drought analog stress was related to the increased activities of sucrose
phosphate synthase, sucrose synthase, acid invertase, and neutral invertase,
increased transcript levels of VIN1, CIN1, NIN1, SUT2, SUT4, and SUT5, and
increased activities of superoxide dismutase and peroxidase in the leaves. The
greater antioxidant defense capacity of PC and its relationship with saccharide
metabolism was one of the reasons for the improved drought tolerance. In
conclusion, PEPC effectively alleviated oxidative damage and enhanced the drought
tolerance in rice plants, which were more related to the increase of the
endogenous saccharide decomposition. These findings show that components of C4
photosynthesis can be used to increase the yield of rice under drought
conditions.
PMID- 28415034
TI - Validation of a new mortality risk prediction model for people 65 years and older
in northwest Russia: The Crystal risk score.
AB - BACKGROUND: Prediction models help to make decisions about further management in
clinical practice. This study aims to develop a mortality risk score based on
previously identified risk predictors and to perform internal and external
validations. METHODS: In a population-based prospective cohort study of 611
community-dwelling individuals aged 65+ in St. Petersburg (Russia), all-cause
mortality risks over 2.5 years follow-up were determined based on the results
obtained from anthropometry, medical history, physical performance tests,
spirometry and laboratory tests. C-statistic, risk reclassification analysis,
integrated discrimination improvement analysis, decision curves analysis,
internal validation and external validation were performed. RESULTS: Older adults
were at higher risk for mortality [HR (95%CI)=4.54 (3.73-5.52)] when two or more
of the following components were present: poor physical performance, low muscle
mass, poor lung function, and anemia. If anemia was combined with high C-reactive
protein (CRP) and high B-type natriuretic peptide (BNP) was added the HR (95%CI)
was slightly higher (5.81 (4.73-7.14)) even after adjusting for age, sex and
comorbidities. Our models were validated in an external population of adults 80+.
The extended model had a better predictive capacity for cardiovascular mortality
[HR (95%CI)=5.05 (2.23-11.44)] compared to the baseline model [HR (95%CI)=2.17
(1.18-4.00)] in the external population. CONCLUSION: We developed and validated a
new risk prediction score that may be used to identify older adults at higher
risk for mortality in Russia. Additional studies need to determine which targeted
interventions improve the outcomes of these at-risk individuals.
PMID- 28415035
TI - Serum high-density lipoprotein cholesterol concentration and functional state:
The Korean Urban Rural Elderly (KURE) Study.
AB - BACKGROUND: Functional state and cholesterol metabolism are important for older
adults; however, this association has not been fully investigated among community
dwelling older adults. Thus, we investigated the association of HDL cholesterol
with multiple functional state measures in an elderly Korean population. METHODS:
This cross-sectional analysis included 3514 participants, aged 65 years or older,
who participated in baseline health assessment for the Korean Urban Rural Elderly
cohort study from 2012 to 2015. HDL cholesterol concentration was analyzed using
both continuous and categorical variables. Functional state was assessed by the
mini-mental state examination (MMSE), activities of daily living (ADL) scale,
instrumental activities of daily living (IADL) scale, timed up-and go (TUG) test,
and chair-rise test (CRT). Multiple logistic regression models were used to
investigate independent association between HDL cholesterol and functional state,
after adjusting for sex, age, body mass index, systolic blood pressure, fasting
glucose, lipid-lowering drug, history of cancer and cardiovascular disease, and
health behaviors. RESULTS: HDL cholesterol concentration was significantly
associated with MMSE, ADL, IADL, TUG, and CRT in the unadjusted model. After
adjustment for covariates, the association remained significant for MMSE
(standardized beta=0.059, p=0.001), ADL (standardized beta=-0.053, p=0.004), and
CRT (standardized beta=-0.037, p=0.037). In fully-adjusted model, Participants
who had a lower HDL concentration (<40mg/dL) showed significantly increased odds
for having MMSE decline (OR 1.451, 95% CI 1.119-1.883) and ADL dependency (OR
2.251, 95% CI 1.119-4.526), compared reference group (>=60mg/dL). CONCLUSIONS:
Higher HDL cholesterol concentration was associated with better functional state
among Korean older adults.
PMID- 28415036
TI - Toxic effects of glyphosate on diploid and triploid fin cell lines from Misgurnus
anguillicaudatus.
AB - We examined the toxic effects of glyphosate on diploid (DIMF) and triploid (TRMF)
fin cell lines from the Oriental Weather Loach Misgurnus anguillicaudatus. The
LC50 values of glyphosate estimated by methylthiazolyldiphenyl-tetrazolium
bromide (MTT) assay were 315.34 and 371.77 mg/L for DIMF and TRMF, respectively.
Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities in DIMF
and TRMF cells gradually increased and then decreased with increasing glyphosate
concentrations, reaching a maximum at 240 mg/L glyphosate. In contrast,
acetylcholinesterase (AChE) activities in DIMF and TRMF decreased with increasing
concentrations of glyphosate in a concentration-dependent manner. SOD and AChE
activities were generally significantly higher in TRMF compared with DIMF cells
(P < 0.05). The rates of micronucleus and abnormal nuclei were significantly
higher in DIMF and TRMF groups treated with 80-560 mg/L glyphosate compared with
the control groups (P < 0.01). The highest micronuclei rates in both DIMF and
TRMF cells (both 4.300/00) occurred at 400 mg/L glyphosate. There were no
differences in the rates of micronuclei and abnormal nuclei between DIMF and TRMF
cells at any glyphosate concentration. Cell damage, including chromatin
condensation, nucleus distortion, and broken and reduced endoplasmic reticulum,
mitochondria, and ribosomes, were found in both cells treated with the LC50
concentration of glyphosate. Moreover, vacuolization and apoptotic bodies
occurred in glyphosate-exposed DIMF and TRMF cells, indicating apoptosis. These
results indicate that glyphosate in the range of tested concentrations represent
a potential risk to loach through inhibiting proliferation of diploid and
triploid cell lines and induces micronuclei and apoptosis.
PMID- 28415037
TI - Enantiomer-specific accumulation and depuration of alpha-hexabromocyclododecane
(alpha-HBCDD) in chicken (Gallus gallus) as a tool to identify contamination
sources.
AB - A LC-ESI(-)-HRMS method dedicated to the analysis of 6 HBCDD enantiomers at trace
levels in animal matrices was developed, using a cellulose based stationary phase
with a particle size of 2.5 MUm. This method was applied to a sample set derived
from a kinetic study of alpha-HBCDD previously conducted in fast- and slow
growing chickens (Gallus gallus domesticus, n = 49, plus controls), in order to
study the enantiomer specific accumulation and depuration of alpha-HBCDD in
various tissues. Regarding abdominal adipose tissue, muscle and liver, the
average enantiomeric fractions of alpha-HBCDD (EFalpha) for continuously exposed
groups ranged between 0.434 and 0.467, with standard deviations below 0.014,
showing a significant enrichment in (-)alpha enantiomer even accentuated for slow
growing individuals during depuration with EFalpha reduced by about 0.020.
Similar trends were observed for pooled plasma. Then, EFalpha of circulating
plasma alpha-HBCDD appeared to closely reflect EFalpha in storage tissues and
liver, suggesting some equilibrium. The racemic elimination of alpha enantiomer
in excreta during the contamination phase indicated that no preferential
gastrointestinal absorption took place. By contrast, preferential excretion of (
)alpha-HBCDD from the circulating compartment to the intestinal lumen occurred
during the depuration. Finally, the method was applied to samples collected in
three chicken farms, selected for total HBCDD levels in muscle in the ng/g range,
as a tool to determine whether the contamination occurred ante- or post-mortem,
according to the chiral signature. Ante-mortem contamination was hypothesised for
2 farms, with feed being excluded as contamination source.
PMID- 28415038
TI - Adsorption of diclofenac onto goethite: Adsorption kinetics and effects of pH.
AB - The adsorption of diclofenac (DCF), one of the widely used non-steroidal anti
inflammatory drugs, onto the surface of goethite was investigated with batch
experiments. The adsorption at different pH values (5.3, 7.4, and 10.0) were well
fitted with the pseudo-second-order model. The results showed that the adsorption
of DCF onto goethite was strongly depended on solution pH. The amount of adsorbed
DCF decreased with increasing pH duo to electrostatic repulsive interactions.
Fourier transform infrared (FTIR) results indicated that carboxyl group (COOH)
might be involved in the adsorption, and DCF formed bidentate chelate and
bridging bidentate complexes on the surface of goethite.
PMID- 28415039
TI - Removal of fluoride, SDS, ammonia and turbidity from semiconductor wastewater by
combined electrocoagulation-electroflotation.
AB - Semiconductor industry effluents contain organic and inorganic pollutants, such
as sodium dodecyl sulfate (SDS), fluoride and ammonia, at high levels which
consists a major environmental issue. A combined EC-EF process is proposed as a
post-treatment after precipitation for simultaneous clarification and removal of
pollutants. In EC step, a hybrid Fe-Al was used as the soluble anode in order to
avoid supplementary EC step. EC-Fe is more suitable for SDS removal; EC-Al is
more suitable for fluoride removal, while EC with hybrid Al-Fe makes a good
compromise. Clarification and ammonia oxidation were achieved in the EF step.
Effects of anodic material, initial pH, current, anion nature, chloride
concentration and initial pollutant concentration were studied. The final
concentrations may reach 0.27, 6.23 and 0.22 mg L-1 for SDS, fluoride and ammonia
respectively. These concentrations are far lower than the correspondent discharge
limits. Similarly, the final turbidity was found 4.35 NTU which is lower than
5NTU and the treated water does not need further filtration before discharge.
Furthermore, the EC-EF process proves to be sufficiently energy-efficient with
less soluble electrode consumption.
PMID- 28415040
TI - Green fluorescent proteins induce oxidative stress in cells: A worrisome new
wrinkle in the application of the GFP reporter system to biological systems?
PMID- 28415041
TI - Environmental exposures to lead, mercury, and cadmium among South Korean
teenagers (KNHANES 2010-2013): Body burden and risk factors.
AB - INTRODUCTION: Limited information is available on the association of age and sex
with blood concentrations of heavy metals in teenagers. In addition, factors such
as a shared family environment may have an association. We analyzed data from the
Korean National Health and Nutrition Examination Survey (KNHANES, 2010-2013) to
determine whether blood levels of heavy metals differ by risk factors such as
age, sex, and shared family environment in a representative sample of teenagers.
METHODS: This study used data obtained in the KNHANES 2010-2013, which had a
rolling sampling design that involved a complex, stratified, multistage,
probability-cluster survey of a representative sample of the non
institutionalized civilian population in South Korea. Our cross-sectional
analysis was restricted to teenagers and their parents who completed the health
examination survey, and for whom blood measurements of cadmium, lead, and mercury
were available. The final analytical sample consisted of 1585 teenagers, and 376
fathers and 399 mothers who provided measurements of blood heavy metal
concentrations. RESULTS: Male teenagers had greater blood levels of lead and
mercury, but sex had no association with blood cadmium level. There were age
related increases in blood cadmium, but blood lead decreased with age, and age
had little association with blood mercury. The concentrations of cadmium and
mercury declined from 2010 to 2013. The blood concentrations of lead, cadmium,
and mercury in teenagers were positively associated with the levels in their
parents after adjustment for covariates. CONCLUSION: Our results show that blood
heavy metal concentrations differ by risk factors such as age, sex, and shared
family environment in teenagers.
PMID- 28415042
TI - Determinants of increasing serum POPs in a population at high risk for
cardiovascular disease. Results from the PREDIMED-CANARIAS study.
AB - Persistent organic pollutants (POPs) are well-known ubiquitous environmental
chemicals which have been related to adverse health outcomes, including
cardiovascular disease (CVD). The purpose of this study was to evaluate POPs
burden, and its determinants, in a population at high risk of suffering CVD
enrolled in the PREDIMED Study (Spanish acronym for PREvention by means of
MEDiterranean Diet). This cohort was formed by 343 participants (55-80 y.o.),
which were selected for a preventive nutritional intervention for CVD based on
the Mediterranean Diet. Relevant information on demographic, behavioral, dietary,
and socioeconomic characteristics was obtained from each participant through a
specific questionnaire, and their anthropometric and clinical measurements were
recorded. In addition, the levels of 35 POPs were determined in serum samples
taken before the beginning of the nutritional intervention. All the samples
showed detectable levels of, at least, one POP, being DDT-derivatives and marker
PCBs the most frequently detected compounds. Our results showed that people at
high risk for CVD showed a higher level of contamination by POPs as compared to
other studies done in cohorts of Western people at no special risk of CVD.
Although educational level seems to be a relevant determinant for POPs burden in
our population, the main determining factor seems to be the diet. Thus, while the
intake of food of animal origin was significantly associated with levels of PCBs,
especially in men, the intake of vegetal-origin food was positively related to
levels of organochlorine pesticides, indicating a different dietary source for
these two groups of chemicals. Our results showing that subjects at high risk for
cardiovascular disease present elevated POPs burden might have a relevant public
health impact given the generalized and difficult to avoid exposure to POPs and
the elevated worldwide frequency of the CVD.
PMID- 28415043
TI - Environmental stressors as a driver of the trait composition of benthic
macroinvertebrate assemblages in polluted Iberian rivers.
AB - We used the trait composition of macroinvertebrate communities to identify the
effects of pesticides and multiple stressors associated with urban land use at
different sites of four rivers in Spain. Several physical and chemical stressors
(high metal pollution, nutrients, elevated temperature and flow alterations)
affected the urban sites. The occurrence of multiple stressors influenced aquatic
assemblages at 50% of the sites. We hypothesized that the trait composition of
macroinvertebrate assemblages would reflect the strategies that the assemblages
used to cope with the respective environmental stressors. We used RLQ and fourth
corner analysis to address the relationship between stressors and the trait
composition of benthic macroinvertebrates. We found a statistically significant
relationship between the trait composition and the exposure of assemblages to
environmental stressors. The first RLQ dimension, which explained most of the
variability, clearly separated sites according to the stressors. Urban-related
stressors selected taxa that were mainly plurivoltine and fed on deposits. In
contrast, pesticide impacted sites selected taxa with high levels of egg
protection (better egg survival), indicating a potentially higher risk for egg
mortality. Moreover, the trait diversity of assemblages at urban sites was low
compared to that observed in pesticide impacted sites, suggesting the
homogenization of assemblages in urban areas.
PMID- 28415044
TI - Long non-coding RNA SNHG1 regulates zinc finger E-box binding homeobox 1
expression by interacting with TAp63 and promotes cell metastasis and invasion in
Lung squamous cell carcinoma.
AB - The long non-coding RNAs (lncRNAs) have been recently shown to participate in the
progression of a variety of cancers. However, the biological role of lncRNAs and
the underlying mechanisms in Lung squamous cell carcinoma (SCC) or lung
adenocarcinoma (AD) remain unclear. Herein, we investigated expression of 5
lncRNAS (SNHG1, NCBP2-AS2, LINC01206, SOX2-OT and LINC01419) in SCC and AD
tissues. SNHG1 was one of over-expressed lncRNAs in SCC tissues. Knockdown of
SNHG1 significantly inhibited the proliferation, metastasis, invasive ability and
induced apoptosis of SCC cells. Moreover, SNHG1 affected the expression of zinc
finger E-box binding homeobox 1(ZEB1), which has also been observed to be up
regulated in SCC and to promote cell metastasis and invasion. Rather than direct
interaction, SNHG1 regulated ZEB1expression by suppressing the activity of p63 TA
isoform (TAp63), which is a repressor of ZEB1 and physically associates with
SNHG1. Furthermore, SNHG1 promoted ZEB1 expression and promoted cell
proliferation, metastasis, invasive but inhibited apoptosis of SCC cells via the
TAp63/ZEB1 pathway. Taken together, our findings suggested that SNHG1 might play
an oncogenic role in SCC through ZEB1 signaling pathway by inhibiting TAp63 and
might serve as a valuable prognostic biomarker and therapeutic target for SCC
patients.
PMID- 28415045
TI - Knockdown of PEBP4 suppresses proliferation, migration and invasion of human
breast cancer cells.
AB - Phosphatidylethanolamine-binding protein 4 (PEBP4), a member of the PEBP family,
plays a pivotal role in tumor progression. However, the roles of PEBP4 in breast
cancer remain unclear. Therefore, in the present study, we investigated the
effects of PEBP4 on breast cancer cell proliferation, migration and invasion, and
the underlying mechanism was also explored. Our results showed that the
expression of PEBP4 was significantly up-regulated in breast cancer cell lines.
Knockdown of PEBP4 inhibited breast cancer cell proliferation in vitro and tumor
growth in vivo. Furthermore, knockdown of PEBP4 suppressed breast cancer cell
migration and invasion with prevented EMT. Mechanistically, knockdown of PEBP4
inhibited breast cancer cell proliferation and migration through the inactivation
of PI3K/Akt signaling pathway. In conclusion, the present study demonstrated for
the first time that knockdown of PEBP4 inhibited the proliferation, invasion and
tumorigenesis in breast cancer cells. Thus, PEBP4 may serve as a potential
therapeutic target for the treatment of breast cancer.
PMID- 28415047
TI - PLOD2 in cancer research.
AB - Collagen is not only the most abundant protein providing the scaffold for
assembly of the extracellular matrix (ECM), but also considered to be the
"highway" for cancer cell migration and invasion depending on the different
collagen organizations. The accumulation of stabilized collagen is enhanced by
different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the
PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen
cross-link. Interestingly, PLOD2 is overexpressed in different cancers and
closely related to a poor prognosis. To the best of our knowledge, only the
mechanisms of PLOD2 regulated by HIF-1alpha, TGF-beta and microRNA-26a/b have
been elaborated. In addition, several pharmacologic inhibitors of PLOD2 have been
confirmed to have an anti-metastasis effect. However, there have been no reviews
about PLOD2 in cancer research published thus far. In brief, this review about
PLOD2 will describe the function, regulatory mechanism, and the inhibitors of
PLOD2 in cancer, suggesting the credible clinical evaluation of a prognostic
signature in pathological examination and the possible development of therapeutic
strategies targeting PLOD2 in the future.
PMID- 28415046
TI - Cost-benefit effectiveness of angiotensin-II receptor blockers in patients with
uncomplicated hypertension: A comparative analysis.
AB - OBJECTIVE: The treatment of hypertensive patients (HTs) requires a long-term
commitment of compliance for the patient and resources by the healthcare system.
This poses an economic dilemma in countries where universal healthcare is
standard. The aim of this study was to evaluate the costs/health benefit and
effectiveness of treatment with angiotensin-II receptor blockers (ARBs) in
uncomplicated essential hypertension. DESIGN AND METHODS: The daily and annual
economic commitment for treating patients with ARBs was estimated using pharmacy
dispensing records and the BP-lowering effects of candesartan, irbesartan,
losartan, olmesartan, telmisartan and valsartan was evaluated retrospectively. In
114 HTs (mean age 59.4+/-13.5year, 57.5% men), the BP-lowering effect of ARBs as
in monotherapy and in fixed-dose combination (FDC) with hydrochlorothiazide at
the doses commonly used in the market to reach BP control (i.e. BP <140/90mmHg)
was analyzed. The BP lowering-effect was evaluated after an average of 6-month
follow-up consulting medical professionals. Analysis of variance for repeated
measures was provided. RESULTS: Treatment with candesartan (14.1%) and olmesartan
(32,4%) versus other ARBs resulted in a significant decrease in BP as for mono-
than for FDC therapy. Our studies suggest that daily (data not shown) and annual
costs of olmesartan were higher than candesartan as in mono- (4577.71+/-1120.55
vs. 894.25+/-127.75 ?) than for FDC therapy (5715.90+/-459.90 vs. 1580.45+/
113.15 ?). CONCLUSIONS: Treatment: of BP with candesartan appears to be the most
favorable option in terms of cost-effectiveness coupled with favorable health
outcomes. These data have some limitations, but open the question if candesartan
should be preferred to olmesartan in BP management. Further prospective studies
comparing ARBs based on their effect on BP control in uncomplicated HTs are
needed for validation.
PMID- 28415048
TI - Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via
PI3K/Akt/NF-kappaB pathway.
AB - Baicalein, a bioactive flavonoid, exhibits anti-inflammatory and anti-cancer
activities. However, few studies reported the interaction of baicalein with
chemotherapeutic agents. Our study showed that baicalein significantly enhanced
the chemosensitivity of cisplatin (CDDP) in vivo and in vitro. We found that
A549/CDDP (resistant to CDDP) cells not only acquired epithelial-mesenchymal
transition (EMT) phenotype, but also showed increased NF-kappaB activity compared
with A549 cells (sensitive to CDDP). Our study further demonstrated that
PI3K/Akt/NF-kappaB pathway controlled CDDP resistance via EMT and NF-kappaB
mediated apoptosis. Baicalein significantly suppressed the PI3K/Akt/NF-kappaB
pathway, leading to conversion of EMT to mesenchymal-epithelial transition (MET,
the reciprocal mesenchymal to epithelial transition), and inhibition of NF-kappaB
mediated antiapoptotic proteins in A549/CDDP cells. In conclusion, our study
demonstrated that baicalein reversed the resistance of human A549 lung
adenocarcinoma cells to cisplatin by inhibiting EMT and attenuating apoptosis via
PI3K/Akt/NF-kappaB pathway.
PMID- 28415049
TI - Metamorphosis and transition between developmental stages in European eel
(Anguilla anguilla, L.) involve epigenetic changes in DNA methylation patterns.
AB - The life history of the European eel (Anguilla anguilla, L.) is characterized by
a series of metamorphoses and transitions that provoke drastic morphological
changes. Most of these changes go along with the catadromous life cycle in eels,
involving extensive physiologically adaptations. In this study it was
investigated whether these drastic changes have an epigenetic basis by analyzing
global methylation patterns in liver, gill and brain tissue from glass eels
caught at the British coast as well as yellow and silver eels from River Rhine
using methylation-sensitive amplified polymorphisms (MSAP). Analysis of molecular
variance (AMOVA) on MSAP data derived from liver tissue revealed only minor
differences in methylation patterns between glass, yellow and silver eels,
reflecting uniform functioning of the liver throughout the investigated lifespan.
In brain and gill tissue, however, marked differences in methylation patterns
were found. Principal coordinates analysis (PCoA) revealed yellow eels being
partially clustered with silver eels and a more distinct cluster of glass eels
based on the methylation patterns in the brain. According to results found in the
gills, glass eels were more similar to silver eels whereas yellow eels were found
to be clustered separately. From these results it can be concluded that
epigenetic changes in gill tissue most likely reflect and are linked with
adaptation towards salt- and freshwater conditions. The observed differences in
brain methylation patterns, however, might be linked to morphological and
physiological changes during metamorphosis and transitions within the life
history of European eels potentially affecting subsequent differential gene
expression patterns required for such changes.
PMID- 28415050
TI - Free radicals and polyphenols: The redox chemistry of neurodegenerative diseases.
AB - The oxidation of bioorganic materials by air and, particularly, the oxidative
stress involved in the cell loss and other pathologies associated with
neurodegenerative diseases (NDs) are of enormous social and economic importance.
NDs generally involve free radical reactions, beginning with the formation of an
initiating radical by some redox, thermal or photochemical process, causing
nucleic acid, protein and lipid oxidations and the production of harmful
oxidative products. Physically, persons afflicted by NDs suffer progressive loss
of memory and thinking ability, mood swings, personality changes, and loss of
independence. Therefore, the development of antioxidant strategies to retard or
minimize the oxidative degradation of bioorganic materials has been, and still
is, of paramount importance. While we are aware of the importance of
investigating the biological and medical aspects of the diseases, elucidation of
the associated chemistry is crucial to understanding their progression, heading
to intelligent chemical intervention to find more efficient therapies to prevent
or delay the onset of the diseases. Accordingly, this review aims to provide the
reader with a chemical base to understand the behavior and properties of the
reactive oxygen species involved and of typical radical scavengers such as
polyphenolic antioxidants. Some discussion on the structures of the various
species, their formation, chemical reactivities and lifetimes is included. The
ultimate goal is to understand how, when and where they form, how far they travel
prior to react, which molecules are their targets, and how we can, eventually,
control their activity to minimize their impact by means of chemical methods.
Recent strategies explore chemical modifications of the hydrophobicity of potent,
natural antioxidants to improve their efficiency by fine-tuning their
concentrations at the reaction site.
PMID- 28415051
TI - Cross-interference of two model peroxisome proliferators in peroxisomal and
estrogenic pathways in brown trout hepatocytes.
AB - Peroxisome proliferators cause species-specific effects, which seem to be
primarily transduced by peroxisome proliferator-activated receptor alpha
(PPARalpha). Interestingly, PPARalpha has a close interrelationship with
estrogenic signaling, and this latter has already been promptly activated in
brown trout primary hepatocytes. Thus, and further exploring this model, we
assess here the reactivity of two PPARalpha agonists in direct peroxisomal routes
and, in parallel the cross-interferences in estrogen receptor (ER) mediated
paths. To achieve these goals, three independent in vitro studies were performed
using single exposures to clofibrate - CLF (50, 500 and 1000MUM), Wy-14,643 - Wy
(50 and 150MUM), GW6471 - GW (1 and 10MUM), and mixtures, including PPARalpha
agonist or antagonist plus an ER agonist or antagonist. Endpoints included gene
expression analysis of peroxisome/lipidic related genes (encoding apolipoprotein
AI - ApoAI, fatty acid binding protein 1 - Fabp1, catalase - Cat, 17 beta
hydroxysteroid dehydrogenase 4 - 17beta-HSD4, peroxin 11 alpha - Pex11alpha,
PPARalphaBb, PPARalphaBa and urate oxidase - Uox) and those encoding estrogenic
targets (ERalpha, ERbeta-1 and vitellogenin A - VtgA). A quantitative
morphological approach by using a pre-validated catalase immunofluorescence
technique allowed checking possible changes in peroxisomes. Our results show a
low responsiveness of trout hepatocytes to model PPARalpha agonists in direct
target receptor pathways. Additionally, we unveiled interferences in estrogenic
signaling caused by Wy, leading to an up-regulation VtgA and ERalpha at 150MUM;
these effects seem counteracted with a co-exposure to an ER antagonist. The
present data stress the potential of this in vitro model for further exploring
the physiological/toxicological implications related with this nuclear receptor
cross-regulation.
PMID- 28415053
TI - [Treatment Types and Optimal Age for Craniosynostosis].
PMID- 28415052
TI - Viral gene products actively promote latent infection by epigenetic silencing
mechanisms.
AB - Many viruses undergo an acute infection in the host organism and then are cleared
by the ensuing host immune response, but other viruses establish a persistent
infection involving a latent infection or a chronic infection. Latent infection
by the herpesviruses or human immunodeficiency virus involves epigenetic
silencing of the DNA genome or proviral genome, respectively. Latent infection
was previously thought to be a default pathway resulting from infection of a
nonpermissive cell, but recent studies have shown that viral gene products can
promote epigenetic silencing and latent infection. This review will summarize the
viral gene products that have been shown to promote epigenetic silencing of the
genomes and their potential for therapeutics to target these viral gene products
and disrupt or lock in latent infection.
PMID- 28415054
TI - [Hemodialysis Increases the Incidence of Post-Traumatic Seizure in Hemodialysis
Patients with Traumatic Intracranial Hemorrhage].
AB - BACKGROUND: In Japan, the number of hemodialysis patients increases every year,
along with the average age of this patient population. Further, certain
complications of hemodialysis make the care of traumatic head injury(THI)patients
particularly difficult. OBJECTIVE: This study was aimed at investigating the
occurrence of and risk factors for post-traumatic seizures in hemodialysis
patients with a history of THI, and determining patient outcomes. METHODS:
Subjects were selected from patients who were admitted to Yaizu Municipal
Hospital in Shizuoka, Japan for traumatic intracranial hemorrhage(TICH).
Retrospective medical histories of TICH patients who were and were not receiving
hemodialysis were reviewed to investigate the risk factors for seizures and to
determine patient outcomes. RESULTS: We identified 18 THI patients on
hemodialysis and 86 THI patients not on hemodialysis treatment. We determined
that predictive factors of post-traumatic seizure include:current hemodialysis
treatment, enlargement of an existing hematoma, and an acute subdural hematoma.
Moreover, 66.7% of seizures in our dialysis patients occurred during
hemodialysis. Our data also suggest that Glasgow Coma Scale(GCS)scores on
admission are a predictive factor for patient outcomes following discharge.
CONCLUSION: Current hemodialysis treatment, enlargement of an existing hematoma,
and an acute subdural hematoma are predictive factors of seizure occurrence in
THI patients. As post-traumatic seizures triggered unfavorable outcomes in some
dialysis patients, it is important to create appropriate plans for preventing
dialysis disequilibrium syndrome that may lead to seizures in TICH/TIH patients
on hemodialysis. We also determined that a low GCS score upon admission is a
significant predictor of unfavorable outcomes.
PMID- 28415055
TI - [Risk Factors for Predicting the Need for Additional Surgery for Symptomatic
Adjacent Segment Disease after Minimally Invasive Surgery-Transforaminal Lumbar
Interbody Fusion].
AB - PURPOSE: To determine the incidence of and risk factors for symptomatic adjacent
segment disease(SASD)requiring additional surgery in patients previously treated
with minimally invasive surgery-transforaminal lumbar interbody fusion(MIS
TLIF)for degenerative lumbar disease. MATERIALS AND METHODS: A series of 467
consecutive patients who had undergone MIS-TLIF of one or two segments to treat
degenerative lumbar disease was identified. The mean age of the patients at the
time of the index operation was 67.7 years and the mean follow-up period was 33.2
months(range, 6.0-110.1 months). The incidence rate of SASD surgeries was
calculated using the Kaplan-Meier method. The log-rank test and Cox regression
analysis were used for risk factor analysis based on age, sex, number of fused
segments, presence of laminectomy adjacent to index fusion, and L1 plumb line.
RESULTS: The overall incidence rate of SASD requiring additional surgery was
2.8%. Kaplan-Meier analysis predicted a disease-free rate of adjacent segments in
94.3% of the patients at 4 years and in 90.8% of the patients at 8 years after
the index operation. In the analysis of risk factors, a negative L1 plumb line
was associated with a 5.6 times higher incidence of SASD requiring additional
surgery than that associated with a positive L1 plumb line(p=0.0096). There was
no significant difference in the survival rates based on age, sex, number of
fused segments, and concomitant laminectomy to adjacent segment. CONCLUSION:
Approximately 9.2% of the patients were predicted to undergo additional surgery
for treating SASD within 8 years of MIS-TLIF. In this study, presence of a
negative L1 plumb line indicated higher incidence of additional SASD associated
surgeries than that shown by a positive L1 plumb line. Therefore, surgeons should
carefully consider this factor while performing MIS-TLIF.
PMID- 28415056
TI - [Pulsatile Tinnitus due to an Aberrant Internal Carotid Artery in the Middle
Ear:A Case Report].
AB - We report a rare case of aberrant internal carotid artery in the middle ear. The
patient was a 30-year-old man with pulsatile tinnitus. MRA and 3D-CTA revealed an
aberrant course of the internal carotid artery in the middle ear. 3D-CTA proved
useful for radiographic diagnosis, leading to the observation of an aberrant
internal carotid artery passing the foramen. We discuss the diagnosis and
management of such patients.
PMID- 28415057
TI - [De Novo Cavernous Angioma Secondary to a Developmental Venous Anomaly:A Case
Report and Review of the Literature].
AB - OBJECTIVE: Previously, cavernous angiomas(CAs)have been thought to be only
congenital in origin. Recently, however, a few cases of de novo CAs have been
reported in the literature. We present a case of a de novo CA and discuss the
etiology of the newly appeared CA. CASE REPORT: A 29-year-old man was presented
to a local clinic because of hypersomnia. MRI demonstrated a heterogeneous mass
peripherally located, which was in contact with a developmental venous
anomaly(DVA)at the left thalamus. Six years before the presentation, he visited
the same clinic because of faintness, and MRI results indicated no abnormality
except for the DVA. Three weeks later, he suddenly experienced difficulty in
speech, and the MRI revealed an increase in the size of the mass. Subsequently,
he was admitted at our institution, and neurological examination revealed aphasia
and right hemiparesis. A left carotid angiogram on venous phase showed a
narrowing of the DVA, which was seen as it entered the internal cerebral vein.
The diagnosis of a de novo CA was made. The mass was completely resected through
the transcallosal transventricular approach to avoid injuring the DVA. The DVA
could not be found during surgery. The pathological diagnosis was in line with
the findings of CA. Postoperatively, the patient continued having difficulty in
speech and was transferred to another institution for speech rehabilitation.
CONCLUSIONS: Although the association of CA and DVA has been described with
increasing frequencies recently, the etiology of de novo CA in the case of this
association has been a matter of debate. In the present case, it was speculated
that a narrowing of the DVA resulted in increased venous pressure and caused the
development of de novo CA.
PMID- 28415058
TI - [A Case of Arteriovenous Malformation of the Parotid Gland Associated with Cowden
Disease].
AB - We report a rare case of arteriovenous malformation(AVM)of the parotid gland
associated with Cowden disease successfully treated with preoperative
embolization followed by surgical removal. A 39-year-old man with a history of
Cowden disease presented with a pulsating and growing mass on his left lower jaw.
Contrast-enhanced computed tomography(CT)and angiography revealed a high-flow AVM
in the deep lobe of the left parotid gland. After intravascular embolization of
the feeding arteries, surgery was performed using the NIM
response(r)3.0, facial nerve monitoring system. The AVM was almost
completely removed and the facial nerves were morphologically preserved.
Interestingly, the intraoperative findings revealed that the enlarged vasa
nervorum of the facial nerve also fed the AVM. Although left facial nerve palsy
appeared after the surgery, the nerve function gradually improved over one year.
No recurrence of the AVM has been observed for one year.
PMID- 28415059
TI - [A Case of Slowly Progressive Brain Metastasis with Minor Bleeding after Removal
of and Chemotherapy for Non-Small Cell Lung Cancer].
AB - Of all brain metastases, the most common primary lesion is derived from the lung.
These types of metastases enlarge aggressively with unfavorable prognoses. We
report the case of a 75-year-old male patient who had a history of pulmonary
resection for Stage IA non-small cell lung cancer(NSCLC), and received
chemotherapy. One year after NSCLC surgery, he experienced a cardiogenic cerebral
infarction, and anticoagulant therapy was initiated. Mass lesions with hemorrhage
were detected bilaterally in the frontal lobes through magnetic resonance imaging
three years after the NSCLC surgery. The lesions slowly enlarged during follow
up. However, there were no clinical symptoms. There was no finding indicating a
local recurrence or metastasis through positron emission tomography(PET). Two and
a half years after the detection of the lesion, left hemiplegia was observed.
Massive hemorrhage from the right frontal lobe lesion was observed on computed
tomography(CT). Craniotomy and evacuation of the hematoma were performed. The
histopathological findings showed adenocarcinoma and the diagnosis was brain
metastasis of the lung cancer. This case reveals brain metastasis of lung cancer
that progressed without extracranial metastases for three years. The brain tumor
enlarged, accompanied by hemorrhage, extremely slowly without any symptoms. It
was difficult to differentiate between metastasis and cavernous hemangioma,
considering the extremely slow progress and image analyses. Of the reported
prognostic factors associated with postoperative brain metastasis from surgically
resected NSCLC, three factors were applicable to this case:adenocarcinoma, a
small number of brain metastases, and the absence of extracranial metastases at
the diagnosis of brain metastasis. We should consider the possibility of a
metastatic brain tumor secondary to lung cancer even long after thoracic surgery.
PMID- 28415060
TI - [A Case of Foramen Magnum Meningioma Manifesting as Hypoglossal Nerve Palsy].
AB - We report a case of foramen magnum meningioma manifesting as hypoglossal nerve
palsy. A 72-year-old woman presented with progressive hypoglossal nerve palsy and
lingual atrophy on the left side. Gadolinium-enhanced T1-weighted magnetic
resonance imaging revealed a heterogeneously enhanced mass lesion with dural tail
sign partially extending into the hypoglossal canal. The transcondylar approach
was performed to expose the hypoglossal canal and resect the tumor completely.
Histological examination revealed a transitional meningioma. The postoperative
course was uneventful. Hypoglossal nerve palsy improved gradually after the
operation.
PMID- 28415061
TI - [A Case of Subarachnoid Hemorrhage with Multiple Cerebral Aneurysms with a
Difficult-to-Identify Rupture Site].
PMID- 28415062
TI - [Pre- and Intra-Operative Supporting Technology for Brain
Tumors(6)Cerebellomedullary Fissure Approach for Fourth Ventricle Tumors].
PMID- 28415064
TI - Physical Demands of Multimodal Training Competitions and Their Relationship to
Measures of Performance.
AB - Jagim, AR, Rader, O, Jones, MT, and Oliver, JM. Physical demands of multimodal
training competitions and their relationship to measures of performance. J
Strength Cond Res 31(5): 1212-1220, 2017-The purpose of this study was to
identify the physical demands of multimodal training (MMT) competitions and to
determine the extent of their relationship to select measures of performance.
Eighteen (>1.5 years of strength training experience) men (n = 10) and women (n =
8) (mean +/- SD; age: 37.8 +/- 10.6 years, height: 172.8 +/- 8 cm, weight: 77.4
+/- 13.2 kg, 16.6 +/- 6% body fat) with experience performing MMT participated in
a simulated MMT competition. All participants were assessed for body composition,
countermovement vertical jump, and aerobic capacity during baseline testing. All
participants then participated in a simulated MMT-style competition on a separate
day within 10 days of baseline testing. The simulated MMT-style competition
consisted of 3 events with 90 minutes of recovery allowed in between events.
During the events, changes in blood lactate (La), heart rate (HR), and estimated
V[Combining Dot Above]O2 were recorded. Bivariate (Pearson) correlations were
computed to determine if a relationship existed between traditional measures of
performance and those of the MMT-style competition. Significance was set at p <=
0.05. Mean change in La ranged between 9 and 12 mmol.L during the events. Mean HR
and estimated V[Combining Dot Above]O2 values ranged from 145 to 172 b.min and 24
to 35 ml.kg.min, respectively, during the events. A strong correlation was
observed (r = -0.722; p < 0.001) between aerobic capacity and time to completion
for event 1. There was a strong correlation between lean body mass and lower-body
strength performance (r = 0.882; p < 0.001) and time to completion for event 3 (r
= -0.792; p < 0.001). A strong correlation was observed between lower-body power
and time to completion for event 1 (r = -0.755; p < 0.001) and event 3 (r =
0.818; p < 0.001). Based on the results of this study, MMT-style competitions
appear to be physically demanding activities performed at a high intensity with a
great involvement of the anaerobic energy system and that some measures of
aerobic capacity and power correlate with performance. When training for MMT
style competitions, it may be beneficial to focus on improving lower-body power
and/or aerobic capacity.
PMID- 28415063
TI - Neuron-restrictive silencer factor-mediated downregulation of MU-opioid receptor
contributes to the reduced morphine analgesia in bone cancer pain.
AB - Bone cancer pain has been reported to have unique mechanisms and is resistant to
morphine treatment. Recent studies have indicated that neuron-restrictive
silencer factor (NRSF) plays a crucial role in modulating the expression of the
MU-opioid receptor (MOR) gene. The present study elucidates the regulatory
mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma
inoculated murine model, pain behaviors that represent continuous or breakthrough
pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and
spinal dorsal horn was quantified at the transcriptional and translational
levels, respectively. Additionally, chromatin immunoprecipitation assays were
used to detect NRSF binding to the promoter of MOR. Furthermore, NRSF was
genetically knocked out by antisense oligodeoxynucleotide, and the expression of
MOR and the effect of morphine were subsequently analyzed. Our results indicated
that in a sarcoma murine model, NRSF expression is upregulated in dorsal root
ganglion neurons, and the expression of NRSF mRNA is significantly negatively
correlated with MOR mRNA expression. Additionally, chromatin immunoprecipitation
analysis revealed that NRSF binding to the neuron-restrictive silencer element
within the promoter area of the MOR gene is promoted with a hypoacetylation state
of histone H3 and H4. Furthermore, genetically knocking down NRSF with antisense
oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic
morphine analgesia. The present results suggest that in sarcoma-induced bone
cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of
morphine analgesia. Epigenetically, up-regulation of MOR could substantially
improve the effect of system delivery of morphine.
PMID- 28415065
TI - Acute Effect of Biomechanical Muscle Stimulation on the Counter-Movement Vertical
Jump Power and Velocity in Division I Football Players.
AB - Jacobson, BH, Monaghan, TP, Sellers, JH, Conchola, EC, Pope, ZK, and Glass, RG.
Acute effect of biomechanical muscle stimulation on the counter-movement vertical
jump power and velocity in division I football players. J Strength Cond Res
31(5): 1259-1264, 2017-Research regarding whole body vibration (WBV) largely
supports such training augmentation in attempts to increase muscle strength and
power. However, localized biomechanical vibration has not received the same
attention. The purpose of this study was to assess peak and average power before
and after acute vibration of selected lower-body sites in division I athletes.
Twenty-one subjects were randomly assigned to 1 of 2 conditions using a cross
over design. Pretest consisted of a counter-movement vertical jump (VJ) followed
by either localized vibration (30 Hz) to 4 selected lower-body areas or 4 minutes
of moderately low-resistance stationary cycling (70 rpm). Vibration consisted of
1 minute bouts at each lower-leg site for a total of 4 minutes followed by an
immediate post-test VJ. Repeated measures analysis of variance yielded no
significant differences (p > 0.05) in either peak power or peak velocity.
Similarly, no significant differences were found for average power and velocity
between conditions. It should be noted that, while not significant, the vibration
condition demonstrated an increase in peak power and velocity while the bike
condition registered slight decreases. Comparing each of the post-VJ repetitions
(1, 2, and 3) the vibration condition experienced significantly greater peak
power and velocity from VJ 1 to VJ 3 compared with the bike condition which
demonstrated no significant differences among the post-test VJs. These results
yielded similar, although not statistically significant outcomes to previous
studies using WBV. However, the novelty of selected site biomechanical vibration
merits further investigation with respect to frequency, magnitude, and duration
of vibration.
PMID- 28415066
TI - Effect of Barbell Weight on the Structure of the Flat Bench Press.
AB - Krol, H and Golas, A. Effect of barbell weight on the structure of the flat bench
press. J Strength Cond Res 31(5): 1321-1337, 2017-In this study, we have used the
multimodular measuring system SMART. The system consisted of 6 infrared cameras
and a wireless module to measure muscle bioelectric activity. In addition, the
path of the barbell was measured with a special device called the pantograph. Our
study concerns the change in the structure of the flat bench press when the
weight of the barbell is increased. The research on the bench press technique
included both the causes of the motion: the internal structure of the movement
and the external kinematic structure showing the effects of the motion, i.e., all
the characteristics of the movement. Twenty healthy, male recreational weight
trainers with at least 1 year of lifting experience (the mean +/- SD = 3.3 +/-
1.6 years) were recruited for this study. The subjects had a mean body mass of
80.2 +/- 8.6 kg, an average height of 1.77 +/- 0.08 m, and their average age was
24.7 +/- 0.9 years. In the measuring session, the participants performed
consecutive sets of a single repetition of bench pressing with an increasing load
(about 70, 80, 90, and 100% of their 1 repetition maximum [1RM]). The results
showed a significant change in the phase structure of the bench press, as the
barbell weight was increased. While doing the bench press at a 100% 1RM load, the
pectoralis major changes from being the prime mover to being the supportive prime
mover. At the same time, the role of the prime mover is taken on by the
deltoideus anterior. The triceps brachii, in particular, clearly shows a greater
involvement.
PMID- 28415067
TI - Effect of Whey Protein in Conjunction With a Caloric-Restricted Diet and
Resistance Training.
AB - Dudgeon, WD, Kelley, EP, and Scheett, TP. Effect of whey protein in conjunction
with a caloric-restricted diet and resistance training. J Strength Cond Res
31(5): 1353-1361, 2017-Caloric-restricted weight loss, especially rapid weight
loss, results from a decrease in both lean and fat mass (FM). The goal for many
is to lose FM while retaining lean body mass (LBM) and muscular performance thus
many turn to supplements. Sixteen resistance-trained men (24 +/- 1.6 years of
age) completed a 4 d.wk body building style split resistance training program for
8 weeks in conjunction with a pre-exercise, periexercise, and postexercise
ingestion of whey protein (WHEY) nutritional supplement or carbohydrate (CON)
based nutritional supplement. There were no differences in body mass change
between the WHEY and CON groups although both groups lost body mass (p <= 0.05);
however, WHEY group maintained LBM whereas the CON group lost (p <= 0.05), and
the WHEY group lost FM (p > 0.05) and the CON group did not, although the change
in FM between groups was not different. Both the WHEY and CON (p <= 0.05) groups
significantly increased lower-body strength. The WHEY group increased upper-body
strength (p <= 0.05), whereas the CON did not change. Both groups (p <= 0.05)
increased lower-body repetitions to fatigue with the increase greater in the CON
group (p <= 0.05). The CON group also increased upper-body repetitions (p <=
0.05) whereas WHEY did not. WHEY group lost body mass, composed of FM, whereas
CON also experienced a loss in body mass, but this loss was due to decrease in
LBM. Neither group experienced a loss in muscle performance, with the WHEY group
tending to show improvement in strength and CON group in endurance. These data
indicate WHEY supplementation compared with carbohydrate supplementation, during
a caloric-restricted "cut" diet can assist in maintaining LBM while allowing for
the loss of FM.
PMID- 28415068
TI - Validity and Reliability of a Portable Isometric Mid-Thigh Clean Pull.
AB - James, LP, Roberts, LA, Haff, GG, Kelly, VG, and Beckman, EM. Validity and
reliability of a portable isometric mid-thigh clean pull. J Strength Cond Res
31(5): 1378-1386, 2017-This study investigated the test-retest reliability and
criterion validity of force-time curve variables collected through a portable
isometric mid-thigh clean pull (IMTP) device equipped with a single-axial load
cell. Fifteen males with >=6 months of resistance training experience attended
two testing sessions. In each session, participants performed an IMTP in 2
separate conditions in a randomized counterbalanced manner. The criterion
condition consisted of a closed-chain IMTP configured with a force plate (IMTPf),
whereas the experimental test was undertaken using a portable IMTP with data
acquired through a single-axial load cell (IMTPl). A very high reliability
(coefficient of variation [CV] = 3.10, 90% confidence interval [CI]: 2.4-4.6%;
intraclass correlation coefficient [ICC] = 0.96, 90% CI: 0.90-0.98) and
acceptable validity (CV = 9.2, 90% CI: 7-14%; ICC = 0.88, 90% CI: 0.71-0.95) were
found in the experimental condition for the measure of peak force. However,
significant differences were present between the IMTPf and IMTPl (p < 0.0001).
Alternate force-time curve variables did not reach acceptable levels of validity
or reliability in the experimental condition. The IMTPl is a valid and highly
reliable method for assessing peak force. This provides evidence supporting the
use of an IMTPl as a cost-effective and portable alternative for those who wish
to assess maximal force production in a similar fashion to a traditional IMTP.
However, practitioners should be aware that these are slightly different tests.
PMID- 28415070
TI - Game Times and Higher Winning Percentages of West Coast Teams of the National
Football League Correspond With Reduced Prevalence of Regular Season Injury:
Erratum.
PMID- 28415069
TI - Comparison of Bioimpedance and Underwater Weighing Body Fat Percentage Before and
Acutely After Exercise at Varying Intensities.
AB - Nickerson, BS, Esco, MR, Kliszczewicz, BM, and Freeborn, TJ. Comparison of
bioimpedance and underwater weighing body fat percentage before and acutely after
exercise at varying intensities. J Strength Cond Res 31(5): 1395-1402, 2017-The
purpose of this study was to compare single-frequency bioelectrical impedance
analysis (BIA) and bioimpedance spectroscopy (BIS) with underwater weighing (UWW)
body fat percentage (BF%) before (PRE), immediately post (IP), and 60 minutes
post (60P) an acute bout of moderate and vigorous aerobic exercise. Nine men (age
= 24.6 +/- 3.7 years) volunteered for this study. Subjects visited the laboratory
on 3 separate occasions. Testing included two 30-minute exercise sessions at 60
and 80% heart rate reserve (HRR) and a 30-minute control (CON) trial. The
constant error (CE) was significantly higher for BIA at each time point and
exercise session (CE = 3.0-4.9% for 60% HRR; 2.5-4.7% for 80% HRR). Conversely,
BIS yielded a nonsignificant CE at each time point and exercise session (CE =
0.9 to 1.1% for 60% HRR; -0.3 to 1.2% for 80% HRR). The standard error of
estimate (SEE) for both exercise sessions ranged from 2.7 to 3.1% and 3.8-4.3%
for BIA and BIS, respectively. The 95% limits of agreement were narrower for BIA
(60% HRR = +/-5.5 to 7.8%; 80% HRR = +/-6.6 to 8.5%) than BIS (60% HRR = +/-8.4
to 9.4%; 80% HRR = +/-8.1 to 10.2%). Results indicate that BIS can be used for
mean group BF% in men at PRE, IP, and 60P time periods. However, BIA yielded a
lower SEE and 95% limits of agreement than BIS. Therefore, BIA provides better
individual estimates of BF% in men, but the CE should be taken into
consideration.
PMID- 28415071
TI - Lower Physical Activity in Persons with Multiple Sclerosis at Increased Fall
Risk: A Cross-sectional Study.
AB - Persons with multiple sclerosis (MS) often report being afraid of falling, and
this may have effects on physical activity (PA) engagement. This study
investigated PA levels in persons with MS as a function of fall risk categories.
Forty-seven persons with MS participated in the study and were categorized into
either increased fall risk (IFR; n = 21; 55.5 +/- 9.0 years) or normal fall risk
(NFR; n = 26; 51.2 +/- 12.9 years) groups based on scores from the Activities
Balance Confidence scale. PA was measured by accelerometer and expressed as
average steps per day, and time spent in sedentary behavior, light PA, and
moderate to vigorous physical activity over the course of 7 consecutive days.
Univariate and covariate analyses were used to compare the differences in PA
between fall risk groups. The average steps per day of the NFR group was
significant higher compared with the IFR group (6024 +/- 2533.1 vs. 2599 +/-
1622.7 steps; P < 0.001), and the difference remained after controlling for
disability level (5351 +/- 2298.6 vs. 3432 +/- 2363.6 steps; P = 0.016). There
were no differences in light PA and moderate to vigorous physical activity
between groups after controlling for disability level. Persons with MS at IFR
accumulate fewer steps per day compared with those at NFR. This underscores the
need for well-designed interventions targeting walking in this population who are
far from the recommended 10,000 steps, particularly those with IFR.
PMID- 28415072
TI - Changing Perception: Outcomes from a Physical Medicine and Rehabilitation Medical
Student Interest Fair.
AB - Exposure to the field of Physical Medicine and Rehabilitation (PM&R) is limited
in the curricula of many medical schools. As a result, many students lack
awareness of the field and may therefore ultimately choose different careers. A
medical student PM&R career fair was held on October 13th, 2015 at the University
of Pittsburgh, and several local medical schools were invited to participate.
Seven stations were deployed to highlight various aspects of PM&R careers. A
total of 57 medical students attended, representing five different campuses
across three states, with 29 of the reported medical students still within their
first or second year of medical education. Self-reported interest and
understanding of PM&R significantly increased in those attending the fair
compared to baseline, with nearly half requesting further opportunities for
faculty mentorship. These results indicate that PM&R interest fairs may be a
means to further student understanding and awareness of PM&R while providing an
opportunity to become more involved in the field.
PMID- 28415073
TI - Chemical-induced disease relation extraction via convolutional neural network.
AB - : This article describes our work on the BioCreative-V chemical-disease relation
(CDR) extraction task, which employed a maximum entropy (ME) model and a
convolutional neural network model for relation extraction at inter- and intra
sentence level, respectively. In our work, relation extraction between entity
concepts in documents was simplified to relation extraction between entity
mentions. We first constructed pairs of chemical and disease mentions as relation
instances for training and testing stages, then we trained and applied the ME
model and the convolutional neural network model for inter- and intra-sentence
level, respectively. Finally, we merged the classification results from mention
level to document level to acquire the final relations between chemical and
disease concepts. The evaluation on the BioCreative-V CDR corpus shows the
effectiveness of our proposed approach. Database URL:
http://www.biocreative.org/resources/corpora/biocreative-v-cdr-corpus/.
PMID- 28415074
TI - NaviCom: a web application to create interactive molecular network portraits
using multi-level omics data.
AB - : Human diseases such as cancer are routinely characterized by high-throughput
molecular technologies, and multi-level omics data are accumulated in public
databases at increasing rate. Retrieval and visualization of these data in the
context of molecular network maps can provide insights into the pattern of
regulation of molecular functions reflected by an omics profile. In order to make
this task easy, we developed NaviCom, a Python package and web platform for
visualization of multi-level omics data on top of biological network maps.
NaviCom is bridging the gap between cBioPortal, the most used resource of large
scale cancer omics data and NaviCell, a data visualization web service that
contains several molecular network map collections. NaviCom proposes several
standardized modes of data display on top of molecular network maps, allowing
addressing specific biological questions. We illustrate how users can easily
create interactive network-based cancer molecular portraits via NaviCom web
interface using the maps of Atlas of Cancer Signalling Network (ACSN) and other
maps. Analysis of these molecular portraits can help in formulating a scientific
hypothesis on the molecular mechanisms deregulated in the studied disease.
Database URL: NaviCom is available at https://navicom.curie.fr.
PMID- 28415082
TI - P210Long- term outcome of primary mitral valve prolapse: results from a
population of 250 patients referred to a tertiary cardiovascular center.
AB - Background: Outcome of Mitral Valve Prolapse (MVP) was controversial for long
time. Many studies reported great differences in the incidence of cardiovascular
events due, above all, to heterogeneous and small studied populations. Most of
theme were also published to late '80 of the last century till early '00.
Purpose: To make a contemporary survey on the incidence of cardiovascular events
in a selected population of patients affected by primary MVP referred to a
tertiary cardiovascular center for the medical and surgical care of valvular
heart disease. Methods: We reviewed our MVP database; patients with at least 2
cardiologic evaluations inclusive of echocardiographic examination and at least 6
months follow up were enrolled. A total of 250 patients (126 F) were selected.
Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up
time was 100 months (8,33 yrs). Results: At the first medical and
echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR),
104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a
severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA
III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP
(94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was
present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%)
and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior
mitral annulus diameter was 37 mm. During the follow up 7 patients died of non
cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary
syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally
we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture
occurred during the follow up in most cases concerning mitral chordae linked to
posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an
evolution of the clinical condition of 48 patients (19.2%) which developed
Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of
the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at
the initial evaluation). A total of 45 patients (18%) underwent mitral valve
surgery. 40 needed in-hospital treatment in most cases due to the development of
atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred
in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6
(2.4%). The overall cardiovascular event rate was 4,33/100 patients-year,
significantly higher than reported in community based studies. Conclusions: The
prognosis of a MVP population referred to a tertiary cardiovascular center is not
benign. The most frequent complications are progression of MR and MV surgery.
Sudden death is also more frequent than in general population. More studies are
needed to identify what patients with MVP are at risk for it.
PMID- 28415075
TI - HopBase: a unified resource for Humulus genomics.
AB - Hop (Humulus lupulus L. var lupulus) is a dioecious plant of worldwide
significance, used primarily for bittering and flavoring in brewing beer. Studies
on the medicinal properties of several unique compounds produced by hop have led
to additional interest from pharmacy and healthcare industries as well as
livestock production as a natural antibiotic. Genomic research in hop has
resulted a published draft genome and transcriptome assemblies. As research into
the genomics of hop has gained interest, there is a critical need for centralized
online genomic resources. To support the growing research community, we report
the development of an online resource "HopBase.org." In addition to providing a
gene annotation to the existing Shinsuwase draft genome, HopBase makes available
genome assemblies and annotations for both the cultivar "Teamaker" and male hop
accession number USDA 21422M. These genome assemblies, gene annotations, along
with other common data, coupled with a genome browser and BLAST database enable
the hop community to enter the genomic age. The HopBase genomic resource is
accessible at http://hopbase.org and http://hopbase.cgrb.oregonstate.edu.
PMID- 28415083
TI - P235Relation between myocardial deformation by three-dimensional speckle tracking
analysis , control of the hypertension and functional capacity in patients with
systemic hypertension.
AB - The purpose of this study was to investigate left ventricular (LV) function in
hypertensive patients by 3-dimensional (3D) speckle tracking imaging, and
determine the relation between the LV mechanics and functional capacity in this
population. This cross-sectional study included 20 treated subjects with well
controlled arterial hypertension (group B) and 20 treated participants with
uncontrolled hypertension (group A), adjusted by gender and age. All the subjects
underwent 24-hour blood pressure monitoring, complete 2-dimensional and 3D
examination, and exercise testing. Patients had similar 3D LV ejection fraction.
LV mass was higher in group of uncontrolled hypertension (154.71 +/- 49.7 g/m2
versus 147.12+/-44.8 g/m2 p < 0.01), as well as E/E'ratio (11.4 versus 8.9, p
=0.02). 3D global longitudinal and circumferential strain and strain rate were
significantly decreased in patients with inadequately controlled hypertension (LS
16.25% versus -19.24%, p=0.007, L-SR -0.97/sec versus -1.48/sec, p=0.04, CS
17.89%versus -21.76%, p=0.04, respectively), while the difference of radial
strain and strain rate did not reach statistical significance. Group A of
patients had also a significantly lower functional capacity (mean duration of
test 13,3 min. versus 17,4 min, nr. of METS 9.4 versus 13.7). Duration of
exercise was independently associated with LV mass , mean BP at daytime , E/E'
ratio and 3D global longitudinal strain (beta = 0.34, p = 0.02) in the whole
hypertensive population in our study. In conclusion, LV longitudinal strain and
functional capacity are significantly impaired in the patients with uncontrolled
hypertension in comparison with the well-controlled hypertensive patients and are
independently associated.
PMID- 28415084
TI - P260Right cardiac chambers remodeling in marathon and ultra-trail athletes
detected by speckle-tracking echocardiography.
AB - Background: Strenuous and chronic exercise training can have detrimental effects
on cardiac morphology and function. Our aim was to evaluate the cardiac
adaptation between 2 different specialties' endurance athletes: marathon runners
(M) and ultra-trailers (UT). Methods: 47 M (age 45+/-7, men 32; training: 18 (9
53) years*days/week), 41 UT (age 42+/-9, men 38, training: 30 (15-66)
years*days/week) were submitted in rest condition to conventional 2D
echocardiography and Speckle-Tracking echo (STE) (Beyond Diogenes 2.0, AMID)
during agonistic season and compared with 15 age matched sedentary individuals
(S) (age 43+/-6, men 10). Results: Left ventricle (LV) global longitudinal strain
(GLS) and global radial strain (GRS) were increased in M and UT compared to S
(see table) without differences in LV anatomy and function. Right ventricle (RV)
end-diastolic area (p=0.026), fractional area changing (p=0.008) and RV GLS were
increased in UT compared to M. Moreover UT showed larger right atrium (RA) volume
compared to M (p=0.03) and S (p=0.003). RA GLS was reduced in UT compared to M
while the RA Global Circumferential Strain was significantly increased in UT.
After adjusted for age, sex and HR as covariates, UT showed a reduced RA GLS (OR
0.907; CI 0.856-0.961) and increased RV FAC (OR 1.172; CI: 1.044-1.317) compared
to M; while when compared to S subjects, UT showed increased RA volume (OR 1.048;
CI 1.002-1.096) and RV GLS (OR 0.667; CI 0.490-0.907). Conclusion: UT showed
higher RV and RA morphological and functional remodeling in comparison with M. 2D
STE is a useful tool to investigate the deformation dynamic in different sport
specialties. Further studies will be necessary to clarify the long-term
consequences for cardiac health due to myocardial perturbations. : MUTSpLV GLS
28.59+/-3.43*-27.64+/-4.18*-24.82+/-4.53<0.05LV GRS69.85+/-8.94*66.59+/
11.19*56.27+/-16.25<0.001RV GLS-25.60+/-10.54-30.41+/-4.38*-27.10+/-4.64<0.05RA
GLS37.15+/-13.4931.65+/-9.60*35.37+/-9.99<0.05RA GCS17.46+/-6.4222.28+/
8.97*23.37+/-6.47<0.01.
PMID- 28415098
TI - P569Diastolic dyssynchrony is associated with exercise intolerance in
hypertensive patients with left ventricular hypertrophy.
AB - Background: Left ventricular hypertrophy (LVH) is associated with intra
ventricular dyssynchrony at systolic phase during exercise in hypertensive
patients. However, dypsnea on exertion is much more correlated with diastolic
phase. We investigated whether LVH is associated with diastolic dyssynchrony
during exercise in patients with hypertension. Methods: Ninety hypertensive
patients with exertional dyspnea and 30 control individuals were enrolled.
Exercise stress echocardiography was performed using a symptom limited,
multistage supine bicycle test. To evaluate the diastolic dyssynchrony of LV, we
calculated the standard deviation (SD) of the averaged time from Q wave to
myocardial early diastolic velocity in 12 segments. (TPe-SD, ms). Therefore,
diastolic dyssynchrony index was SD of TPe. And also, we applied modified SD
(SD/heart rate). Results: There was no significant difference in systolic blood
pressure (BP) and heart rate between the two groups. TPe-SD was significantly
higher in patients with LVH at rest (27 +/- 11.0 vs. 18.7 +/- 7.4 ms, p<0.005)
with exaggeration of the degree at peak exercise (42.0 +/- 10.6 vs. 30.6 +/- 12.4
ms, p<0.001). When applying modified SD, the difference is much more increased
(80.0 +/- 17.6 vs. 49.0 +/- 21.3 ms, p <0.001). Multiple regression analysis
showed LV mass index (beta=0.515, P=0.001) and E/E' at peak exercise (beta=
0.253, P=0.025) were independently associated with LV dyssynchrony during
diastolic phase when controlled for age, sex, and systolic BP at peak exercise.
Conclusion: Intra-ventricular diastolic dyssynchrony during exercise is
significantly associated with exercise duration in hypertensive patients with
LVH. And this result could explain that the patients with exertional dyspnea are
more common in LVH group. : Univariate and multivariate analysis forUnivariate
AnalysisMultivariate Analysisbetap valuebetap valueAge-0.288*0.037
0.355*0.001Sex0.161*0.0200.250*0.034LVMI (g/m2)-0.787*0.008-0.515*0.001LAVI(mL)
0.4400.065-0.1750.075E' at peak ex.0.2160.589Diastolic dyssynchrony-0.725*0.030
0.253*0.025S' at peak ex.0.7100.073 LVMI, left ventricular mass index; LAVI, left
atrium volume index; E, early diastolic mitral inflow velocity; E', early
diastolic longitudinal tissue velocity; S', early systolic longitudinal tissue
velocity. : Univariate and multivariate analysis for. : LVMI, left ventricular
mass index; LAVI, left atrium volume index; E, early diastolic mitral inflow
velocity; E', early diastolic longitudinal tissue velocity; S', early systolic
longitudinal tissue velocity.
PMID- 28415097
TI - P544The importance of contractile reserve when assessing asymptomatic patients
with aortic stenosis.
AB - Asymptomatic patients may exhibit symptoms during objective exercise testing, but
whether symptoms are due to the obstructively of the valve (typified by the mean
gradient) or underlying ventricular function remains unknown. While the mean
gradient is an easy parameter to measure no consensus about the measurement of
contractile reserve exists. Longitudinal abnormalities may occur in the presence
of a normal ejection fraction and the augmentation of these parameters is poorly
described. To obtain an objective regarding patients exercise ability is best
determined using cardiopulmonary exercise testing. We therefore examined
echocardiographic predictors of exercise ability during cardiopulmonary exercise
testing.24 asymptomatic patients with moderate to severe or severe aortic
stenosis and preserved ejection fraction underwent stress echocardiography with
simultaneous cardiopulmonary exercise testing. The primary assessment of exercise
ability was the VO2peak and OUES. Echocardiography was measured at rest and
during maximal exercise (defined as RER > 1)OUES and VO2peak showed a poor
relationship with conventional parameters of severity including peak and mean
gradients, AVA and dimensionless index, resting systolic function (by EF and
TDI). During exercise systolic augmentation had a good relationship with exercise
ability but the exercise mean gradient and exercise LVEF did not.Longitudinal
systolic function and particularly systolic augmentation is the strongest
predictor of exercise ability when compared to conventional measures of
severity.VO2peakOUESS' exerciseRho=0.69 (p=0.001)R= 0.71 (p=0.001)S' restRho=0.52
(p=0.01)R= 0.44 (p=ns)Rest AV max VRho= 0.09 (p=ns)R= -0.08 (p=ns)Rest AV mean
PGRho= 0.34 (p=ns)R=-0.10 (p=ns)Exercise AV max VRho=0.43 (p=0.05)R=0.23
(p=ns)Exercise AVmean PGRho= 0.51 (p=0.001)R=0.26 (p=ns)Rest AVARho=0.40
(p=ns)Rho=0.46 (p=0.04)Dimensionless indexRho=0.15 (p=ns)R=0.13 (p=ns)LVEF
restRho=-0.18 (p=ns)R=-0.32 (p=ns)LVEF exerciseRho=0.18 (p=ns)R=0.17 (p=ns)S' -
systolic velocity; V - velocity; AV - aortic valve; AVA- aortic valve area; LVEF
left ventricular ejection fraction.
PMID- 28415099
TI - P594Contrast transthoracic echocardiography as a gatekeeper for patent foramen
ovale closure.
AB - Background.: The presence of patent foramen ovale (PFO) has been linked to many
illness, including cryptogenic stroke, transient ischemic attack, migraine,
platypnea-orthodeoxia syndrome and decompression sickness in scuba divers.
Transesophageal echocardiography is the gold standard technique for the
visualization of atrial septal anatomy, but it is a secondary level exam, not
always available, with additional associated costs and not completely free from
procedural risks. Standard transthoracic echocardiography (TTE) has a too low
sensitivity for PFO screening. Purpose.: The aim of the study was to assess the
role of TTE associated with agitated saline contrast injection (contrast-TTE) as
a gatekeeper for the identification of PFO in a large cohort of patients
undergoing selection for percutaneous closure. Methods.: A total of 200 patients
undergoing a diagnostic work-up for the identification of PFO was imaged by
contrast-TTE at rest and after provocative maneuvers (PM: Valsalva in all cases).
Contrast TTE was graded from 0 to 4 on the bases of bubbles counting (0: no
bubbles; 1: < 10 bubbles; 2: 10-30 bubbles; 3: >30 bubbles; 4: complete LV
opacification). PFO closure was performed after a consensual clinical decision by
the cardiologist and the neurologist taking into account comprehensive imaging,
clinical evaluation and thrombophilia screening. PFO closure was always monitored
by intracardiac echocardiography. Results.: At baseline contrast TTE was positive
(>=2) in 34 patients (17%) while contrast TTE with PM was positive in 94 cases
(47%). 27 out of 200 patients (14%) had an interatrial septal aneurysms. PFO
closure was performed in 34 cases (17%). All of these had severe right-to-left
shunting (>=3) at contrast TTE and 9 cases had also an interatrial septal
aneurysms. The procedure was aborted in only 1 patient due to a complex defect
anatomy. Conclusion.: Contrast TTE with PM may be not only considered an accurate
tool for the detection of PFO but may be also inserted in the diagnostic work- up
as a primary gatekeeper for percutaneous closure. Severe shunting at contrast TTE
influences final decision making in a large cohort of cases undergoing screening
for PFO closure.
PMID- 28415102
TI - P650Influence of fetunin-a level on progression of calcific aortic valve stenosis
The COFRASA - GENERAC Study.
AB - Background.: In recent years, pathophysiology of aortic stenosis (AS) has been
considered as a possibly active inflammatory process, but its determinants remain
unclear. Calcium tissue deposition observed in dilaysis patients have been linked
to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is
thus suspected to play a role in development of aortic stenosis. Purpose.: To
assess correlation between Fetuin-A level and AS progression in a prospective
cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC
(clinicalTrial.gov_number_NCT00647088). Methods.: A comprehensive clinical
evaluation and Fetuin-A plasma level measurement was performed at baseline. AS
severity was evaluated at baseline and yearly thereafter using echocardiography
(mean pressure gradient (MPG)) and computed tomography (degree of aortic valve
calcification or AVC). Annual progression was calculated as [(final measurement -
baseline measurement)/follow-up duration] for both MPG and AVC measurements.
Results.: We enrolled 296 patients with at least 1 year of follow-up. Mean age
was 74+/-10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55+/-0.15 g/L.
After a mean follow-up of 3.0+/-1.7 years, no correlation was found between AS
progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC
(r=0.014, p=0.82). This was also true when comparing patients with lower level of
Fetuin-A (<=0.53 g/L, the median in our cohort) with patients with higher
level(+3+/-5 mmHg/year (median 2, [0-5] vs +4+/-4 mmHg/year (median 2, [1-6])
p=0.06, and +205+/-290 AUC/year (median 122, [32-269]) vs +240+/-310 AUC/year
(median 145, [50-313], p=0.24). This was true also after adjustment for baseline
severity and valve antomy. Conclusions.: In our prospective cohortot of AS
patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS
progression. Despite strong capacity to inhibit ectopic calcium deposition,
Fetuin-A plasma level seems to have minor influence on AS progression.
PMID- 28415103
TI - P673Improvement of arterial stiffness and myocardial deformation in patients with
poorly controlled diabetes mellitus type 2 after optimization of antidiabetic
medication.
AB - Background: Arterial stiffness is associated with increased risk for
cardiovascular disease. The purpose of this study is to investigate the arterial
stiffness and myocardial deformation in patients with poorly controlled diabetes
mellitus type 2 before and after glycemic control by optimal medication. Methods:
In 50 patients with uncontrolled type 2 diabetes(age:52+/-10years)and 25 controls
of similar age and sex and no atherosclerotic risk factors we measured at
baseline and 6 months after glycemic control a) carotid-femoral pulse wave
velocity(PWVc m/sec-Complior SP ALAM),central systolic blood pressure(cSBP
mmHg),augmentation index(AI%), of the aortic pulse wave(ArteriographTensioMed)
b)S',E'(m/sec)andE'/A'of mitral annulus by Tissue Doppler c)LV longitudinal
strain(GLS-%),systolic(LongSr-l/sec)and diastolic(LongSrE-l/sec)strain rate,
twisting(Tw-deg),peak twisting(Tw)and untwisting(unTw-deg/sec)velocity using
speckle tracking echocardiography.The degree of LV untwisting was calculated as
the percentage difference between peak twisting and untwisting at MVO(%dp PeakTw
UntwMVO)and between peak twisting and untwisting at peak and end of the mitral
inflow E wave d)perfusion boundary region(PBR- micrometers)of the sublingual
arterial microvessels(ranged from 5-25 micrometers)using Sideview,Darkfield
imaging(Microscan,Glycocheck).Increased PBR is considered an accurate index of
reduced endothelial glucocalyx thickness because of a deeper RBC penetration in
the glucocalyx e) Flow mediated dilatation(FMD) of the brachial artery and
percentage difference of FMD (FMD%). Results: Compared to controls,diabetics had
higher PWVa(10.3+/-2.2 vs. 8.1+/-1.9), AI(27.9+/-15 vs. 19.4+/-14.7), PWVc(11.8+/
3.2 vs. 8.8+/-1.3),cSBP(136+/-20 vs. 119+/-18),PBR (2.1+/-0.2 vs 1.89+/-0.1)and
lower GLS(-15+/-3 vs. -18+/-3),LongSr(-0.78+/-0.1 vs. -0.96+/-0.2),LongSrE(0.77+/
0.29 vs. 1.2+/-0.3),S',E' and E/A(p<0.05 for all comparisons). Baseline FMD was
related with Untw at peak E%(r=0,65, p<0.05). Six months after the modification
of antidiabetic medication all patients achieved glycaemic control and there was
a reduction of PWVc(12.3+/-2.9 vs. 11.3+/-3.2,p<0.05) in parallel with a increase
of Untw velocity (-73+/-27 vs. -98+/-43,p<0.05),Untw MVO%(20+/-9 vs. 30+/-2),Untw
peak E% (40+/-14 vs. 50+/-16)and FMD%(7.8+/-3 vs. 13.6+/-11,p<0.01).Reduced PWVc
was related with reduced SBP(r=0.62),cSBP(r=0.55)and increased LongsrE(r=-0.50),
Untw at end E(r=-0.56)respectively(p<0.05 for all associations). Conclusion:
Glycaemic control after optimizing medical treatment improves arterial stiffness,
LV myocardial strain, twisting and untwisting velocity in diabetics.
PMID- 28415104
TI - P697New indices for a best quantification of left ventricular function in heart
valve diseases.
AB - : Aims. : The Assessment of left ventricular (LV) function remains a clinical
challenge especially in patients with preserved LV ejection fraction (EF) and
valvular heart diseases (VHD). Mechanical dispersion is supposed to be a strong
predictor of events and, to be related to the extent of fibrosis. Regional
cardiac work is a new validated and very promising approach to quantify LV
function. : We investigated the differences in mechanical dispersions and global
LV work (totW) and wasted work fraction (WWF) in normal subjects and in patients
with severe primary mitral regurgitation (MR) and severe aortic stenosis (AS).
Methods and Results: A complete transthoracic echocardiography was performed in
21 normal subject, 97 patients with severe valvulopathy (47 AS, 50 MR) and
preserved LV EF. Segmental strain analysis was performed in all patients and the
dispersion of regional LV strain curves was computed automatically considering
peaks and integrals. The LV-pressure was estimated non-invasively using a
standard waveform fitted to valvular events and scaled to systolic blood
pressure. Using pressure-strain loops, regional cardiac work indices were
computed. : LVEF was 66+/-12 in controls, 65+/-9 in MR and 65+/-4% in AS
(p=0.125). Global longitudinal strain was -23+/-2.7 in controls, -24+/-2.9 in MR
and -18+/-3.2% in AS (p < 0.001). The mechanical dispersion was 38+/-7.9 in
controls, 36+/-11 in MR, and much higher in the hypertrophied LV of the AS: 60+/
19ms (p < 0.001). Cardiac work was 2200+/-260 in controls, 2100+/-270 in MR, and
much lower in AS: 1700+/-280 mmHg.% (p < 0.001). The wasted work fraction (WWF)
was even more describing how different the LV systolic function is in the 3
groups (figure1). Conclusion: Longitudinal strain data are robusted and new
indices might be calculated based on them. These seem especially promising for a
more pathophysiological driven analyzing of LV-functions. Abstract P697 Figure. :
Abstract P697 Figure.
PMID- 28415115
TI - P981Lvot area measurement using gated ct data reclassifies aortic stenosis
severity as graded by echocardiography.
AB - Background: Measurement of left ventricular outflow tract (LVOT) diameter and
area for estimation of aortic valve area (AVA) using transthoracic
echocardiography (TTE) and the continuity equation assumes circular LVOT. The use
of direct planimetric measurement of LVOT area by gated-CT can theoretically
improve accuracy of AVA calculation. Purpose: We aim to assess reproducibility of
LVOT echo measurement and its correlation and agreement with Gated CT
measurements. In the subgroup with aortic stenosis (AS) we secondarily assessed
the potential change in AS severity using LVOT area by CT instead of TTE in the
continuity equation. Methods: We retrospectively studied 93 patients, 43 of whom
with severe AS. LVOT Area was measured with 2D TTE by 2 expert echocardiographers
and gated-CT by 2 expert radiologists; inter-reader agreement and inter-method
(Echo vs gated CT) agreement and correlation were measured. Finally we used the
measurement of CT scan in the continuity equation instead of TTE measurement to
assess potential reclassification of AS severity. Results: Mean age was 78+/-11.
Table shows inter-reader and inter-method agreement and correlation. : The
correlation between 2 echocardiophers for LVOT measurements was good (rho = 0,77)
although not perfect. Out of 43 severe AS, defined as AVA<1 cm2 using TTE in the
continuity equation, 18 were reclassified by gated-CT LVOT measurements into
moderate AS. This was due to gated-CT LVOT area resulting on average 1.4 cm2
larger than LVOT area by TTE. Conclusion: LVOT is elliptical and TTE tends to
underestimate LVOT area and AVA due to the measurement of the shorter diameter of
this ellipse. CT scan can provide more geometrically accurate measurement and
requires different cut-offs compared with traditional TTE AVA measurement. By the
way, in the current study the LVOT area by CT was on average 38% larger of the
LVOT area measured by TTE. Such correcting factor (increase TTE LVOT area by 38%)
should apparently be used to assess anatomical true planimetric area to be
compared with gated-CT LVOT. : summary tableTTE Inter-reader correlation LVOT
area (Spearman rho)0.77TTE reader A vs CT 3-chamber equivalent correlation
(Spearman rho)0.49TTE reader B vs CT 3-chamber equivalent correlation (Spearman
rho)0.38TTE reader A area vs CT planimetric area correlation (Spearman
rho)0.41TTE reader B area vs CT planimetric area correlation (Spearman
rho)0.31Mean LVOT Area by TTE reader A3,60SD 0,6038%Mean LVOT Area by CT
scan4,99SD 0,98 Abstract P981 Figure. : summary table. : Abstract P981 Figure.
PMID- 28415116
TI - P1007Aortic root diameters and aortic regurgitation in hypertensive patients and
normal subjects.
AB - Purpose: : The association between aortic root diameters and aortic regurgitation
in hypertension (HT) is disputed with lack of understanding of the underline
mehanisms lT. We investigate the relationship between aortic root diameters and
aortic regurgitation in newly diagnosed and never treated hypertensive patients
and in a group healthy subjects. Method: Participants were 175 hypertensives (42
F and 133 M) and 305 normotensives (134 F, 168 M) age matched (mean age 52.4+/-13
vs 52.6 +/-15.2 years). Antropometric, office blood pressure (BP) measurements, a
comprehensive echocardiography and local carotid stiffness study were performed.
Aortic measures for annulus, sinuses of Valsalva, sinotubular junction and
ascending aorta were taken in late diastole according to the leading edge method.
The sinotubular junction/annulus ratio was calculated. Results: Hypertensive
patients had significantly higher body surface area (BSA), systolic (SBP) and
diastolic pressure (DBP), mean arterial pressure (MAP) and pulse?pressure (PP)
(p<0.0001) than normotensives. Annulus and sinotubular junction diameters,
indexed by BSA and after adjustment for gender, MAP, heart rate?(HR), were
significantly higher in normotensives than hypertensives. Considering subjects
with aortic regurgitation (trivial or mild) we found a higher prevalence
in?hypertensives (25.7 % vs 10.2%, p<0.0001). Moreover in hypertensives we found
no difference in aortic diameters between patients with or without aortic
regurgitation?but ascending aorta /BSA (p=0.002) whereas in healthy subjects
aortic regurgitation was associated with larger aortic root diameters included
sinotubular junction/annulus ratio (table 1). In the logistic regression
analysis, aortic regurgitation was associated with age, gender, BP parameters,
one point carotid stiffness parameters. Conclusions: Hypertensive patients had
smaller indexed aortic root dimensions than normal subjects but they had heigher
prevalence of trivial-mild aortic regurgitation in contrast to normotensives who
had aortic regurgitation combined with larger aortic diameters.
PMID- 28415117
TI - P1033Echocardiographic predictive model of new-onset postoperative atrial
fibrillation after abdominal surgery.
AB - Background: and purpose: Postoperative atrial fibrillation (POAF) is a frequent
complication post high-risk abdominal surgery in elderly patients. This study
aimed to develop a predictive model of POAF based on preoperative transthoracic
echocardiography (TTE) findings in these patients. Methods: We conducted a
prospective study of 300 consecutive patients, age >= 65 years (mean age 72+/-6
years, 61% men), who underwent high-risk abdominal surgery under general
anesthesia. Preoperative TTE was performed in all patients, including tissue
Doppler imaging (TDI). We measured the time interval between the onset of the P
wave on ECG and a point of the peak-A wave on TDI from the lateral mitral annulus
(PA lateral) and septal mitral annulus (PA septal). Left atrial (LA) dyssynchrony
was measured by subtracting the PA septal from PA lateral. Right ventricular
systolic pressure was estimated by using the tricuspid regurgitation jet (TRJ)
Doppler velocity method. The primary endpoint was the occurance of new-onset
POAF. Results: Thirty-seven (12%) patients developed POAF. Multiple
echocardiographic parameters were measured and tested in different combinations.
The final model included the following variables with cutoff points predictive of
POAF: PA lateral > 139 ms (69% sensitivity, 92% specificity), LA dyssynchrony >
35 ms (78% sensitivity, 89% specificity), and TRJ Doppler velocity >2.6 m/s (89%
sensitivity, 64% specificity). A value of 0 was assigned when the result was
below the cutoff point and a value of 1 if above the cutoff point. Coding of
these three variables in the following order: PA lateral- TRJ Doppler- left
atrial dyssynchrony can predict the probability of POAF. The model showed a
postive predictive value of 79% and a negative predictive value of 95%.
Conclusion: A model using three echocardiographic variables: PA lateral, LA
dyssynchrony and TRJ Doppler velocity, can predict the incidence of POAF after
high-risk abdominal surgery. The model can be used preoperatively to identify
high-risk patients that would need aggressive prophylactic treatment. : PA
lateral >139 ms-TRJ Doppler velocity >2.6 m/s-LA dyssynchrony >35 msProbability
of POAF0- 0- 0; 0- 1- 0No0- 0- 1; 0- 1- 1; 1- 0- 0; 1- 0- 1; 1- 1- 0; 1- 1- 1Yes.
PMID- 28415120
TI - P1088Match and mismatch between opening area and resistance in mild and moderate
rheumatic mitral stenosis.
AB - Background: Mitral valve resistance (MVR) is a hemodynamic consequence of mitral
stenosis but it has no clear threshold and it has a shortage of data to be
reliable. Purpose: is to investigate match and mismatch between opening area and
resistance especially in patients with moderate and mild mitral stenosis.
Materials: This cross section case control study comprised 88 patients with
moderate and mild rheumatic mitral stenosis. Transthorathic echocardiographic
study estimated: mitral valve area (MVA) both by planimerty (2D) and pressure
half time (PHT), mitral valve score (MVS), mean transmitral pressure gradient
(MPG), diastolic filling time(DFT), left ventricular out flow tract diameter
(LVOTd) and velocity time integral (LVOT vti) , the MVR was calculated as:
MPG/aortic flow ratio [(LVOTd) (LVOTvti)/ DFT] in dynes.sec.cm5, NYHA function
class of all patients was estimated. We classified our patients into 2 groups,
group 1 (51 patients) with matched MVR and group 2 (37 patients) with unmatched
MVR (unexpected high MVR in relation to valve area). Methods: Patients with
moderate mitral stenosis have MVR less than 105 dynes.sec/cm5, while patient with
mild mitral stenosis have MVR less than 76 dynes.sec/cm5 this is in the matched
group, but there are patients with unmatched higher MVR. Group 2 compared to
group 1; had higher NYHA function class (1.4+/-0.6 vs. 1.2+/-0.4, P < 0.05), MVS
(8.1+/-1.8 vs 7+/-0.9, P < 0.05), MPG (11,3+/-3.7 vs.7.8+/-2.5 mmHg, P < 0.01)
and higher MVR (122.37+/-29.87 vs. 67.18+/-20.12 dynes.sec/cm5 , P < 0.01), MVR
showed positive correlation with MVS (r=0.5, P < 0.05), Step wise logistic
regression analysis showed that MVS is the only independent predictor of the MVR
severity in the mismatched (unexpected high) group , so the higher the MVS the
higher the expected MVR whatever the MVA is ; (B+/-SE=6.997+/-2.826, t=2.476, 95%
CI 1.241+/-12.752 with an odds ratio=0.412, P < 0.05). Conclusion: It would make
much more sense to investigate match and mismatch between opening area and
resistance in rheumatic mitral stenosis, the only independent predictor of
mismatch is the mitral valve score.
PMID- 28415121
TI - P1113Relationship between left atrium and hypertensive retinopathy in patients
with systemic hypertension: a real-time three-dimensional echocardiography-based
study.
AB - Background: The fundoscopic examination of hypertensive patients, which is an
established hypertension-related target organ damage (TOD), tends to be
underutilized in clinical practice. We sought to investigate the relationship
between retinal alterations and left atrium (LA) volumes by means of real-time,
three-dimensional echocardiography (RT3DE), which is the most pivotal predictor
of diastolic dysfunction. Methods: Our population consisted of 88 consecutive
essential hypertensive patients (age 59.2 +/- 1.2 years, 53 females) without
overt cardiovascular disease. All subjects underwent a fundoscopy examination and
were distributed into five groups according to the Keith-Wagener-Barker (KWB)
classification. Comprehensive transthoracic echocardiographic and RT3DE
measurements were performed to assess LA volumes and phasic functions. Results:
The four groups (KWB grades 0-4: including 26, 20, 26, and 16 patients,
respectively) did not differ with regards to age, gender, or metabolic profile.
There were no significant differences between groups with regards to parameters
reflecting left ventricle (LV) systolic function and diastolic dysfunctions in
conventional echocardiography, except isovolemic relaxation time (IVRT) and
deceleration time (DT). Nevertheless, patients in the higher KWB category had
higher values of LA volumes (LA maximal volume, LA minimal volume, preatrial
contraction volume, LA total stroke volume, LA active stroke volume, p< 0.001)
regarding RT3DE (table 1). There is also a significant relationship between
preatrial contraction volume and duration of HT (r: 0.67, p<0.001). Conclusion:
Patients with arterial hypertension were found to have increased LA volume and
impaired atrial compliance and contractility. Moreover, RT3DE identifies early
functional LA changes in these patients better than conventional
echocardiography. Assessment of the hypertensive patient by using RT3DE atrial
volume analysis may facilitate early recognition of TOD, which is such a crucial
determinant of cardiovascular mortality and morbidity in patients with systemic
hypertension.
PMID- 28415122
TI - P1138Cardiac shear wave velocity in healthy individuals.
AB - Background: The closure of the valves generates shear waves in the heart walls.
The propagation velocity of shear waves relates to stiffness. This could
potentially be used to estimate the stiffness of the myocardium, with huge
potential implications in pathologies characterized by a deterioration of the
diastolic properties of the left ventricle. In an earlier phantom study we
already validated shear wave tracking with a clinical ultrasound system in
cardiac mode. Purpose: In this study we aimed to measure the shear waves velocity
in normal individuals. Methods: 12 healthy volunteers, mean age=37+/-10, 33%
females, were investigated using a clinical scanner (Philips iE33), equipped with
a S5-1 probe, using a clinical tissue Doppler (TDI) application. ECG and
phonocardiogram (PCG) were synchronously recorded. We achieved a TDI frame rate
of >500Hz by carefully tuning normal system settings. Data were processed offline
in Philips Qlab 8 to extract tissue velocity along a virtual M-mode line in the
basal third of the interventricular septum, in parasternal long axis view. This
tissue velocity showed a propagating wave pattern after closure of the valves.
The slope of the wave front velocity in a space-time panel was measured to obtain
the shear wave propagation velocity. The velocity of the shear waves induced by
the closure of the mitral valve (1st heart sound) and aortic valve (2nd heart
sound) was averaged over 4 heartbeats for every subject. Results: Shear waves
were visible after each closure of the heart valves, synchronous to the heart
sounds. The figure shows one heart cycle of a subject, with the mean velocity
along a virtual M-mode line in the upper panel, synchronous to the ECG signal
(green line) and phonocardiogram (yellow line) in the lower panel. The slope of
the shear waves is marked with dotted lines and the onset of the heart sounds
with white lines. In our healthy volunteer group the mean velocity of the shear
wave induced by mitral valve closure was 4.8+/-0.7m/s, standard error of 0.14
m/s. The mean velocity after aortic valve closure was 3.4+/-0.5m/s, standard
error of 0.09 m/s. We consistently found that for any subject the velocity after
mitral valve closure was higher than after aortic valve closure. Conclusion: The
velocity of the shear waves generated by the closure of the heart valves can be
measured in normal individuals using a clinical TDI application. The shear wave
induced after mitral valve closure was consistently faster than after aortic
valve closure. Abstract P1138 Figure. : Abstract P1138 Figure.
PMID- 28415127
TI - P1246Age-, body size-, and sex-specific reference values for tricuspid valve
apparatus parameters by real-time three-dimensional transthoracic
echocardiography.
AB - Background: and Purpose-Tricuspid valve (TV) apparatus parameters can vary
significantly with demographic and anthropometric factors and could be useful for
clinical decision making. Our aim was to (1) establish the reference values for
TV apparatus parameters using transthoracic three-dimensional (3D)
echocardiography; (2) investigate the influence of age, sex, and body size on TV
anatomy. : Methods-A total of 180 healthy subjects referred in 2015 to our
institution for a screening transthoracic echocardiography were enrolled (mean
age 49.7+17.4 years, range 20 to 80 years: 30 subjects per age decade were
included in the study, 15 for each gender). A real-time zoom 3D image of the TV
and full volume 3D data set were collected from an apical window including TV
using Philips iE33 and GE Vivid E9 Ultrasound Machines. After acquisition, the 3D
data sets were analysed using 3D Qlab and EchoPAC PC softwares. The volumetric
data set was analysed with multiplanar reformatting function to obtain three
simultaneous orthogonal 2D slices (sagittal, coronal and axial planes). The
following TV parameters were obtained and measured: 1. the 3D diastolic annular
diameters (Major and Minor diameters); 2. the 3D diastolic annular area (TDAA);
3. the Tricuspid annular fractional area changes (TAFAC). Results are presented
as mean +/- SD. Differences between and among groups were tested for significance
using the independent samples t-test and ANOVA test for continuous variables.
Univariate Pearson correlation was used to assess the relation between these
parameters and age, and body size. A p <0.05 was considered significant. :
Results- Minor and major diastolic diameters in overall population were 26.1+/
3.9 and 32.3+/-4.1 mm, respectively. Minor diastolic diameter (mDD) (26.9+/-4.2
vs 25.1+/-3.4 mm, p <0.05) and major diastolic diameter (MDD) (33.4+/-4.0 vs
30.9+/-3.8, p <0.05) were significantly different between males and females.
After normalization for BSA, mDD and MDD in overall population were 14.6+/-2.2
and 18.3+/-2.3 mm/m2. Normalized mDD (14.3+/-2.3 vs 14.9+/-2.2 mm/m2, p >0.05)
and normalized MDD (18.1+/-2.4 vs 18.4+/-2.3 mm/m2, p>0.05) did not differ
significantly between males and females. TTDAA and TAFAC in overall population
were 76.7+/-17.3 mm2 and 29.6+/-8.6%. TDAA was significantly different between
males and females (82.5+/-18.3 vs 69.7+/-13.0 mm2, respectively; p < 0.05);
whereas TAFAC did not differ (28.8+/-8.2% vs 30.7+/-8.9%, p>0.05). After
normalization for BSA, TDAA in overall population was 43.3+/-9.0 mm2/m2. Also
normalized TDAA was significantly different between males and females (44.4+/-9.4
vs 42.0+/-8.4 mm2/m2, p < 0.05). mDD, MDD, TDAA and TAFAC showed no correlation
with age (r = 0.16, p 0.04; r = 0.028, p 0.7; r = 0.17, p 0.27; r = 0.16, p 0.16;
respectively). : Conclusion- This study can provide normal reference values for
TV anatomic parameters that may be useful in the clinical practice, considering
the effects of age, sex, and body size.
PMID- 28415128
TI - P1270Effects of blood pressure variability on layer-specific longitudinal strain
in hypertension.
AB - Background: Our previous study showed sub-epicardial longitudinal strain (EpiLS)
was an independent prognostic factor for worse outcome in regular treated
hypertension but not global longitudinal strain (GLS) and sub-endocardial
longitudinal strain (EndLS). Increased blood pressure variability (BPV) has been
found associated with target organ damage in hypertension. However, effects of
BPV on layer-specific longitudinal strain have not been well studied. Purpose:
The aim of this study was to investigate the effects of different blood pressure
parameters on layer-specific longitudinal strain in hypertension. Methods: This
study included 95 patients (57 men, age 65 +/- 12 years) with uncomplicated
hypertension who have been regularly treated for more than 1 year. Speckle
tracking echocardiography was used for measurement of longitudinal deformation
from 3 apical views of left ventricle. GLS was measured by automated function
imaging (AFI). We further divided into sub-endocardial and sub-epicardial
myocardium and measured their longitudinal strain by manual click-and-draw method
and averaged from 3 apical views. Blood pressure parameters included office
systolic blood pressure (SBP), office diastolic blood pressure (DBP), central SBP
and DBP by tonometry, average 24-hour SBP and DBP, and BPV parameters by
ambulatory blood pressure monitor. BPV parameters included standard deviation of
daytime SBP (DSSD), standard deviation of nighttime SBP (NSSD), standard
deviation of daytime DBP (DDSD), and standard deviation of nighttime DBP (NDSD).
Results: We divided subjects into low and high group according to median level of
each strain. No blood pressure parameters were different between low and high
EndLS group except week difference in NDSD (9.0 +/- 3.4 vs. 7.8 +/- 2.0 mmHg, p =
0.051). NSSD (11.2 +/- 4.6 vs. 9.3 +/- 2.9 mmHg, p = 0.027) and NDSD (9.1 +/- 3.4
vs. 7.7 +/- 2.0 mmHg, p = 0.031) were significant increased in low GLS group but
not other parameters. DDSD (10.3 +/- 3.0 vs. 9.0 +/- 2.5 mmHg, p = 0.034), NSSD
(11.4 +/- 4.4 vs. 9.1 +/- 3.1 mmHg, p = 0.006), and NDSD (9.2 +/- 3.2 vs. 7.6 +/-
2.2 mmHg, p = 0.012) were significantly increased in low EpiLS group.
Conclusions: Only BPV parameters were associated with decreased longitudinal
strain in hypertension. Effects of BPV were majorly noted in EpiLS.
PMID- 28415129
TI - P1294Evaluation of right atrium mechanics and relation with loading conditions by
speckle tracking echocardiography.
AB - Purpose: The aim of this study is to evaluate the right atrial (RA) mechanics and
change in echocardiographic parameters used for assessment of RA by examining the
end stage kidney patients before and after the hemodialysis (HD). Methods:
Patients between 18 and 85 years of age, receiving HD for at least 6 months were
included. The echocardiographic images were obtained before and after
hemodialysis therapy. Two-dimensional speckle tracking strain analysis was
performed for right atrium in 62 patients. Reference points for analysis are set
on the "P" waves. RA reservoir, conduit and contraction phase longitudinal strain
(Figure 1) and strain rates (Figure 2) were calculated. The changes in
echocardiographic methods before and after hemodialysis were examined.
Correlation between volume depletion and change in echocardiographic parameters
were calculated. Results: 62 patients (49.7 +/- 16.9 years of age, 22 women) were
included in study. The mean volume of ultrafiltration was 2958.12 +/- 1050.5 ml .
The chamber sizes RA are decreased after hemodialysis (RA major diameter; 4.74 +/
0.62 cm vs. 4.46 +/- 0.54 cm p<0.001, RA area; 13.8 +/- 3.0 cm2 vs. 10.6 +/- 2.8
cm2 p<0.001). Two dimensional speckle tracking analysis showed that; RA reservoir
phase strain (% 45.60 +/- 10.8 vs. % 38.15 +/- 8.11 p<0.001). RA conduit phase
strain rate (-1.46 +/- 0.82 s-1 vs. -1.2 +/- 0.56 s-1 p<0.001) measurements are
volume dependent. RA reservoir phase strain rate (2.25 +/- 0.65 s- vs. 2.5 +/-
0.54 s-1 p:0.091) RA contraction strain (% -16.73 +/- 6.8 vs. % -16.35 +/- 7.1
p:0.835) and RA contraction strain rate (-2.15 +/- 0.95 s-1 vs. -2.21 +/- 0.72 s
1 p:0.596) are volume independent parameters. RA reservoir phase strain (r=0.332.
p:0.008) showed significant correlation with the ultra filtrated volume.
Conclusion: Strain rates of RA reservoir phase and RA contraction and RA
contraction strain are found to be volume independent measurements obtained by
speckle tracking. Explaining RA mechanics with echocardiography is an easy and
repeatable assessment which also elucidates more about cardiac pathophysiology
and hemodynamics of patients. Moreover defining novel volume independent
parameters for evaluation of RA would contribute to clinical perspectives of
patients. Abstract P1294 Figure. : Abstract P1294 Figure.
PMID- 28415131
TI - Retraction of: abstract P71, In vitro and in vivo direct monitoring of miRNA-22
expression in isoproterenol-induced cardiac hypertrophy by bioluminescence
imaging.
PMID- 28415132
TI - Genetic alterations in mesiodens as revealed by targeted next-generation
sequencing and gene co-occurrence network analysis.
AB - OBJECTIVE: Mesiodens is the most common type of supernumerary tooth which
includes a population prevalence of 0.15%-1.9%. Alongside evidence that the
condition is heritable, mutations in single genes have been reported in few human
supernumerary tooth cases. Gene sequencing methods in tradition way are time
consuming and labor-intensive, whereas next-generation sequencing and
bioinformatics are cost-effective for large samples and target sizes. MATERIALS
AND METHODS: We describe the application of a targeted next-generation sequencing
(NGS) and bioinformatics approach to samples from 17 mesiodens patients. Subjects
were diagnosed on the basis of panoramic radiograph. A total of 101 candidate
genes which were captured custom genes were sequenced on the Illumina HiSeq 2500.
Multistep bioinformatics processing was performed including variant
identification, base calling, and in silico analysis of putative disease-causing
variants. RESULTS: Targeted capture identified 88 non-synonymous, rare, exonic
variants involving 42 of the 101 candidate genes. Moreover, we investigated gene
co-occurrence relationships between the genomic alterations and identified 88
significant relationships among 18 most recurrent driver alterations. CONCLUSION:
Our search for co-occurring genetic alterations revealed that such alterations
interact cooperatively to drive mesiodens. We discovered a gene co-occurrence
network in mesiodens patients with functionally enriched gene groups in the sonic
hedgehog (SHH), bone morphogenetic proteins (BMP), and wingless integrated (WNT)
signaling pathways.
PMID- 28415133
TI - ZO-2, a tight junction protein involved in gene expression, proliferation,
apoptosis, and cell size regulation.
AB - ZO-2 is a peripheral tight junction protein that belongs to the membrane
associated guanylate kinase protein family. Here, we explain the modular and
supramodular organization of ZO-2 that allows it to interact with a wide variety
of molecules, including cell-cell adhesion proteins, cytoskeletal components, and
nuclear factors. We also describe how ZO proteins evolved through metazoan
evolution and analyze the intracellular traffic of ZO-2, as well as the roles
played by ZO-2 at the plasma membrane and nucleus that translate into the
regulation of proliferation, cell size, and apoptosis. In addition, we focus on
the impact of ZO-2 expression on male fertility and on maladies like cancer,
cholestasis, and hearing loss.
PMID- 28415134
TI - An Arctic predator-prey system in flux: climate change impacts on coastal space
use by polar bears and ringed seals.
AB - Climate change is impacting different species at different rates, leading to
alterations in biological interactions with ramifications for wider ecosystem
functioning. Understanding these alterations can help improve predictive capacity
and inform management efforts designed to mitigate against negative impacts. We
investigated how the movement and space use patterns of polar bears (Ursus
maritimus) in coastal areas in Svalbard, Norway, have been altered by a sudden
decline in sea ice that occurred in 2006. We also investigated whether the
spatial overlap between polar bears and their traditionally most important prey,
ringed seals (Pusa hispida), has been affected by the sea-ice decline, as polar
bears are dependent on a sea-ice platform for hunting seals. We attached
biotelemetry devices to ringed seals (n = 60, both sexes) and polar bears (n =
67, all females) before (2002-2004) and after (2010-2013) a sudden decline in sea
ice in Svalbard. We used linear mixed-effects models to evaluate the association
of these species to environmental features and an approach based on Time Spent in
Area to investigate changes in spatial overlap between the two species. Following
the sea-ice reduction, polar bears spent the same amount of time close to tidal
glacier fronts in the spring but less time in these areas during the summer and
autumn. However, ringed seals did not alter their association with glacier fronts
during summer, leading to a major decrease in spatial overlap values between
these species in Svalbard's coastal areas. Polar bears now move greater distances
daily and spend more time close to ground-nesting bird colonies, where bear
predation can have substantial local effects. Our results indicate that sea-ice
declines have impacted the degree of spatial overlap and hence the strength of
the predator-prey relationship between polar bears and ringed seals, with
consequences for the wider Arctic marine and terrestrial ecosystems. Shifts in
ecological interactions are likely to become more widespread in many ecosystems
as both predators and prey respond to changing environmental conditions induced
by global warming, highlighting the importance of multi-species studies.
PMID- 28415135
TI - The effects of enteral feeding improvement massage on premature infants: A
randomised controlled trial.
AB - AIMS AND OBJECTIVES: To prove the effects of an enteral feeding improvement
massage for premature infants with regard to their feeding, growing and superior
mesentery artery blood flow aspect by a randomised controlled trial. BACKGROUND:
Premature infants have feeding-related problems related to eating and absorbing
nutrition due to their immature gastrointestinal function. Studies regarding the
effectiveness of premature infants' enteral feeding improvement by tactile
stimulation massage are rare. DESIGN: The study group was composed of 55
patients. Of the 55 patients, 26 were randomised into an experimental group and
29 were randomised into a control group. METHODS: They were all born <34 weeks of
gestational age between 1 July 2011 and 30 March 2012. Premature infants in the
experimental group received enteral feeding improvement massage twice a day for
14 days, and infants in the control group received a sham exercise. The collected
data were analysed by spss 19.0, through t test, chi-square test (Fisher's exact)
and ANCOVA. RESULTS: (i) The experimental group had reached the day of full
enteral feeding significantly faster. (ii) The experimental group had a higher
superior mesentery artery peak velocity (Vmax ) and lower RI (resistant index).
(iii) The experimental group of the feeding-intolerant subgroup had a higher
superior mesentery artery Vmax and Vmin . (iv) The experimental group had a
heavier weight and larger head circumference after 14 days. CONCLUSIONS: This
study demonstrates that enteral feeding improvement massage can be helpful for
achieving earlier full enteral feeding, more increased superior mesentery artery,
and faster growing. In particular, it can be a therapeutic, independent and
evidence-based nursing intervention for feeding-intolerant premature infants.
RELEVANCE TO CLINICAL PRACTICE: Neonatal nurses in neonatal intensive care unit
can apply enteral feeding improvement massage massage for feeding-intolerant
infants.
PMID- 28415136
TI - Prevalence and descriptive epidemiology of atopic dermatitis and its impact on
quality of life in Singapore.
PMID- 28415137
TI - Drivers of species' role in avian seed-dispersal mutualistic networks.
AB - The mutualistic interaction between frugivore birds and the fruiting plants they
disperse presents an asymmetric interaction pattern, with some species having a
more important role (i.e. being essential) for maintaining the structure and
functioning of the interaction network. The identification of the biological
characteristics of these species is of major importance for the understanding and
conservation of seed-dispersal interactions. In this study, I use a network
approach and avian seed-dispersal networks from 23 different geographical areas
to test five hypotheses about species characteristics determining the structure
of the assemblage. I expected (i) large birds to forage on a large number of
fruits and (ii) large fruits to be dispersed by few bird species (because of
morphological constraints), and (iii) highly energetic fruits to be dispersed by
more bird species (in accordance with optimal foraging theory). Besides the
number of interacting partners, I also expected (iv) large birds and (v) small
energetic fruits to be important for the maintenance of the structure of the
interactions in seed-dispersal networks. As species that are closely related are
more likely to be similar to each other, I performed phylogenetically corrected
analyses to account for this data dependence. Although bird size was not
associated to species important in the maintenance of the structure of the seed
dispersal community, I identified that bird species whose diet was strongly
dependent on fruits were important for the structure of the network. Regarding
the plants, I found that large fruits were dispersed by fewer species, but the
most important attribute to predict the role of a fruit was its energy content
(higher energy, more bird species dispersing the plant, but low-energy fruits
being of conservation concern because they are dispersed by specific species).
The results of this study suggest that the role of the species in seed-dispersal
assemblages seems to be determined by the role of the species as consumers
(frugivory degree for animals) or by their nutritional inputs (energy content for
fruits) rather than by morphological constrains.
PMID- 28415139
TI - Primary nocturnal enuresis: Assessment and treatment at a single referral center.
AB - BACKGROUND: The aim of this study was to investigate the prevalence of primary
monosymptomatic and non-monosymptomatic nocturnal enuresis (PMNE and PNMNE) and
associated factors in a major referral center for NE in Abu Dhabi. METHODS:
Children referred to the Paediatric Continence Clinic, between 2014 and 2016, for
PNE were included in the study. Exclusion criteria were neuropathic bladder,
abnormality of the bladder and bowel, urethral stenosis, neurological and
psychiatric problems, non-completion of the diagnostic protocol, and follow up <6
months. RESULTS: A total of 128 patients were included in the study: 82 boys
(64.1%) and 46 girls (35.9%). A total of 42.7% of boys and 8.7% of girls had
PMNE, and 57.3% of boys and 91.3% of girls had PNMNE. Constipation was present in
46% of patients. In the male PNMNE group, 74.5% had overactive bladder (OAB),
10.6%, dysfunctional voiding (DV); and 14.9%, OAB + DV. In the female PNMNE
group, 35.7% had OAB; 21.4%, DV; 40.5%, OAB + DV; and 2.4%, underactive bladder.
A total of 97% and 86 of children with PMNE and PNMNE, respectively, had
resolution of NE. Boys had a significantly higher incidence of PMNE, and girls,
of DV. CONCLUSION: In Abu Dhabi, NE is often associated with bladder dysfunction
or DV, mostly in girls, and with constipation. High intake of dry, low fiber
foods, along with hot weather and the stress of city living negatively affect the
incidence of fecal retention and of NE. A multimodal approach, including the
treatment of constipation, led to a satisfactory resolution of PNE in almost 90%
of cases.
PMID- 28415140
TI - Imaging modalities for characterising focal pancreatic lesions.
AB - BACKGROUND: Increasing numbers of incidental pancreatic lesions are being
detected each year. Accurate characterisation of pancreatic lesions into benign,
precancerous, and cancer masses is crucial in deciding whether to use treatment
or surveillance. Distinguishing benign lesions from precancerous and cancerous
lesions can prevent patients from undergoing unnecessary major surgery. Despite
the importance of accurately classifying pancreatic lesions, there is no clear
algorithm for management of focal pancreatic lesions. OBJECTIVES: To determine
and compare the diagnostic accuracy of various imaging modalities in detecting
cancerous and precancerous lesions in people with focal pancreatic lesions.
SEARCH METHODS: We searched the CENTRAL, MEDLINE, Embase, and Science Citation
Index until 19 July 2016. We searched the references of included studies to
identify further studies. We did not restrict studies based on language or
publication status, or whether data were collected prospectively or
retrospectively. SELECTION CRITERIA: We planned to include studies reporting
cross-sectional information on the index test (CT (computed tomography), MRI
(magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic
ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle
aspiration)) and reference standard (confirmation of the nature of the lesion was
obtained by histopathological examination of the entire lesion by surgical
excision, or histopathological examination for confirmation of precancer or
cancer by biopsy and clinical follow-up of at least six months in people with
negative index tests) in people with pancreatic lesions irrespective of language
or publication status or whether the data were collected prospectively or
retrospectively. DATA COLLECTION AND ANALYSIS: Two review authors independently
searched the references to identify relevant studies and extracted the data. We
planned to use the bivariate analysis to calculate the summary sensitivity and
specificity with their 95% confidence intervals and the hierarchical summary
receiver operating characteristic (HSROC) to compare the tests and assess
heterogeneity, but used simpler models (such as univariate random-effects model
and univariate fixed-effect model) for combining studies when appropriate because
of the sparse data. We were unable to compare the diagnostic performance of the
tests using formal statistical methods because of sparse data. MAIN RESULTS: We
included 54 studies involving a total of 3,196 participants evaluating the
diagnostic accuracy of various index tests. In these 54 studies, eight different
target conditions were identified with different final diagnoses constituting
benign, precancerous, and cancerous lesions. None of the studies was of high
methodological quality. None of the comparisons in which single studies were
included was of sufficiently high methodological quality to warrant highlighting
of the results. For differentiation of cancerous lesions from benign or
precancerous lesions, we identified only one study per index test. The second
analysis, of studies differentiating cancerous versus benign lesions, provided
three tests in which meta-analysis could be performed. The sensitivities and
specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95%
confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00);
EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to
0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39
to 0.84). The third analysis, of studies differentiating precancerous or
cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which
meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing
precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and
high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence
intervals reflecting the heterogeneity between the studies). The fourth analysis,
of studies differentiating cancerous (invasive carcinoma) from precancerous
(dysplasia) provided three tests in which meta-analysis was performed. The
sensitivities and specificities for diagnosing invasive carcinoma were: CT:
sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97);
EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to
0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI
0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high
grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate
grade dysplasia) provided six tests in which meta-analysis was performed. The
sensitivities and specificities for diagnosing cancer (high-grade dysplasia or
invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity
0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92),
specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to
0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen
200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19
to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI
0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95%
CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous
(invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in
which meta-analysis was performed. The seventh analysis, of studies
differentiating precancerous or cancerous (intermediate- or high-grade dysplasia
or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests
in which meta-analysis was performed. The sensitivity and specificity for
diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity
0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92),
specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of
studies differentiating precancerous or cancerous (intermediate- or high-grade
dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or
benign lesions provided no test in which meta-analysis was performed.There were
no major alterations in the subgroup analysis of cystic pancreatic focal lesions
(42 studies; 2086 participants). None of the included studies evaluated EUS
elastography or sequential testing. AUTHORS' CONCLUSIONS: We were unable to
arrive at any firm conclusions because of the differences in the way that study
authors classified focal pancreatic lesions into cancerous, precancerous, and
benign lesions; the inclusion of few studies with wide confidence intervals for
each comparison; poor methodological quality in the studies; and heterogeneity in
the estimates within comparisons.
PMID- 28415138
TI - The roles of valuation and reward processing in cognitive function and
psychiatric disorders.
AB - In neuroeconomics, valuation refers to the process of assigning values to states
and actions on the basis of the animal's current representation of the
environment, while reward processing corresponds to processing the feedback
received from the environment to update the values of states and actions. In this
article, we review the brain circuits associated with valuation and reward
processing and argue that these are fundamental processes critical to many
cognitive functions. Specifically, we focus on the role of valuation and reward
processing in attention, memory, decision making, and learning. Next, the extant
neuroimaging literature on a number of psychiatric disorders is reviewed (i.e.,
addiction, pathological gambling, schizophrenia, and mood disorders), and an
argument is made that associated deficits in cognitive functions can be explained
in terms of abnormal valuation and reward processing. The review concludes with
the impact of this framework in clinical settings and prescriptions for future
research, in particular with regard to the conversions of qualitatively different
valuation systems into a system of common currency.
PMID- 28415141
TI - Claudin-targeted drug development using anti-claudin monoclonal antibodies to
treat hepatitis and cancer.
AB - The 27-member family of tetraspan membrane proteins known as claudins (CLDNs) is
a major component of tight junctions. A series of studies elucidating the
relationship between CLDNs and various pathological conditions has provided new
insights into drug development. For instance, CLDN-1 may be a potent target for
epidermal absorption of drugs and for treating hepatitis C virus (HCV) infection.
CLDN-4 may be a target for treating cancer. Because CLDNs are also expressed in
various normal tissues, safety and efficacy evaluations are critical for
translational research. We previously developed several anti-CLDN antibodies and
have established proof of concept for CLDN-targeted drug development using these
reagents. Here, we provide an overview of CLDN-1 as a target for improving
epidermal drug absorption and preventing HCV infection and of CLDN-4 as a target
for anticancer therapeutics.
PMID- 28415144
TI - Build the network.
PMID- 28415143
TI - Cardiorespiratory fitness and health-related quality of life in women at risk for
gestational diabetes.
AB - This study examined the associations of cardiorespiratory fitness (CRF) and
leisure-time physical activity (LTPA) with health-related quality of life (HRQoL)
in women at risk for gestational diabetes mellitus (GDM). The participants were
39 women planning pregnancy with a history of GDM and/or BMI >29 kg/m2 . We
assessed CRF by measuring maximal oxygen consumption (VO2max ) during incremental
cycle ergometer exercise until voluntary fatigue. LTPA was self-reported, and
HRQoL assessed with the SF-36 Health Survey (SF-36). The mean (SD) VO2max was 27
(6) mL.kg-1 .min-1 , and the mean LTPA was 2.6 (1.7) h/wk. After controlling for
BMI, VO2max was positively associated with the SF-36 General Health scale (beta
1.27, 95% CI: 0.09, 2.44, P=.035) and the Physical Component Summary (beta 0.48,
95% CI: 0.14, 0.82, P=.007). The General Health scale (P=.023) and the Physical
Component Summary (P=.011) differed even between those with very poor and poor
CRF. After controlling for BMI, LTPA was positively associated with the SF-36
Physical Functioning scale (rs =.34, P=.039), the General Health scale (beta
3.74, 95% CI: 0.64, 6.84, P=.020), and the Physical Component Summary (beta 1.13
95% CI: 0.19, 2.06, P=.020). To conclude, CRF and LTPA were positively associated
with perceived general health and physical well-being in women planning pregnancy
and at risk for GDM. Even a slightly better CRF would be beneficial for well
being among women with low levels of CRF.
PMID- 28415145
TI - Medical marijuana: Challenges and risk issues for health care providers.
AB - Laws on medical marijuana and recreational use of marijuana are sweeping the
country and presenting real dilemmas for health care providers and facilities.
However, due to disagreements between federal and state law, there are no easy
answers. Additionally, the case law and statutory law on these issues is
exceedingly sparse. It may take years for all of the issues to be ironed out, but
health care facilities will need to act in the meantime on what may be little
more than educated guesses. It may not be appropriate to simply prohibit the use
of medical marijuana, but accommodating it also has risk. This article will
address what is known about the subject and what is not known about the subject.
Each provider and health care facility will need to devise their own approach to
the subject based on principles that are presently known, while keeping an eye on
the health and safety of all involved.
PMID- 28415146
TI - A time of uncertainty, a time to step forward.
PMID- 28415142
TI - Neural correlates of cognitive processing in monolinguals and bilinguals.
AB - Here, we review the neural correlates of cognitive control associated with
bilingualism. We demonstrate that lifelong practice managing two languages
orchestrates global changes to both the structure and function of the brain.
Compared with monolinguals, bilinguals generally show greater gray matter volume,
especially in perceptual/motor regions, greater white matter integrity, and
greater functional connectivity between gray matter regions. These changes
complement electroencephalography findings showing that bilinguals devote neural
resources earlier than monolinguals. Parallel functional findings emerge from the
functional magnetic resonance imaging literature: bilinguals show reduced frontal
activity, suggesting that they do not need to rely on top-down mechanisms to the
same extent as monolinguals. This shift for bilinguals to rely more on
subcortical/posterior regions, which we term the bilingual anterior-to-posterior
and subcortical shift (BAPSS), fits with results from cognitive aging studies and
helps to explain why bilinguals experience cognitive decline at later stages of
development than monolinguals.
PMID- 28415147
TI - Neurosurgical laser ablation and MR thermometry: Risks of multisite workflow
pattern.
AB - Neurosurgical laser ablation is a relatively new but rapidly growing application
of stereotactic neurosurgery that allows neurosurgeons to treat many previously
untreatable conditions with the added benefit of shorter hospitalizations and
recovery times. The vast majority of these procedures, however, are performed
using a multisite workflow pattern involving transport of the patient between the
operating room (OR), the computed tomography (CT) suite, and the magnetic
resonance imaging (MRI) suite, often necessitating patient transfer through
public pathways and requiring multiple trips if laser fiber placement is not
accurate. There are significant risks posed to the patient with this practice and
no existing guidelines addressing it. This article serves to identify those risks
and present recommendations for safety optimization and risk reduction for those
health care facilities using a multisite workflow pattern.
PMID- 28415148
TI - The "6 A's": A risk manager's guide to emergency cesarean delivery.
AB - The allegation of delay in performing an emergency cesarean delivery is common in
litigation involving neurological injury to newborns. Analyzing the actual
performance of an emergency cesarean involves multiple steps, individuals, and
systemic processes that need coordination for appropriate action when necessary.
This article gives risk managers a systematic way to evaluate a given perinatal
unit's approach to the ability to perform an emergency cesarean through
evaluating the 6 "A"s: Assess, Alert, Align, Assemble, Act, and Analyze. Each of
these elements is discussed based on current evidence. A checklist that may be
useful in the evaluation of the elements of performance of emergency cesarean
delivery is provided.
PMID- 28415149
TI - Integrating TeamSTEPPS(r) into ambulatory reproductive health care: Early
successes and lessons learned.
AB - BACKGROUND: Most medical teamwork improvement interventions have occurred in
hospitals, and more efforts are needed to integrate them into ambulatory care
settings. In 2014, Affiliates Risk Management Services, Inc. (ARMS), the risk
management services organization for a large network of reproductive health care
organizations in the United States, launched a voluntary 5-year initiative to
implement a medical teamwork system in this network using the TeamSTEPPS model.
This article describes the ARMS initiative and progress made during the first 2
years, including lessons learned. METHODS: The ARMS TeamSTEPPS program consists
of the following components: preparation of participating organizations,
TeamSTEPPS master training, implementation of teamwork improvement programs, and
evaluation. We used self-administered questionnaires to assess satisfaction with
the ARMS program and with the master training course. RESULTS: In the first 2
years, 20 organizations enrolled. Participants found the preparation phase
valuable and were highly satisfied with the master training course. Although most
attendees felt that the course imparted the knowledge and tools critical for
TeamSTEPPS implementation, they identified time restraints and competing
initiatives as potential barriers. The project team has learned valuable lessons
about obtaining buy-in, consolidating the change teams, making the curriculum
relevant, and evaluation. CONCLUSION: Ambulatory care settings require innovative
approaches to integration of teamwork improvement systems. Evaluating and sharing
lessons learned will help to hone best practices as we navigate this new frontier
in the field of patient safety.
PMID- 28415150
TI - Case law update.
PMID- 28415151
TI - Correction.
PMID- 28415152
TI - Oral Candida colonization and oral lichen planus.
PMID- 28415153
TI - Polar and charged extracellular residues conserved among barrier-forming claudins
contribute to tight junction strand formation.
AB - Claudins (Cldn) form the backbone of tight junction (TJ) strands and thereby
regulate paracellular permeability for solutes and water. Polymeric strands are
formed by homo- and heterophilic cis- and trans-interactions between claudin
protomers. Crystal structures of some claudins have been resolved; however, the
mechanism by which claudins assemble into TJ strands remains unclear. To
elucidate strand architecture, TJ-like strands were reconstituted in HEK293 cells
by claudin transfection. Determinants of prototypic, classic barrier-forming
claudins (Cldn1, -3, and -5) involved in strand formation were analyzed by
mutagenesis. The capability of claudin constructs to interact in trans and to
form strands was investigated by cell contact-enrichment assays and freeze
fracture electron microscopy. Residues in extracellular loops 1 and 2 of the
claudins affecting strand formation were identified. Using homology modeling and
molecular docking, we tested working concepts for the arrangement of claudin
protomers within TJ strands. We show that the charge of Lys65 in Cldn1 and Glu158
in Cldn3, but not of Arg30 or Asp145 in Cldn3, and the polarity of Gln56 and
Gln62 in Cldn3 and of Gln57 in Cldn5 are necessary for TJ strand formation. These
residues are all conserved among barrier-forming classic claudins. The results
contribute to mechanistic understanding of claudin-based regulation of
paracellular permeability.
PMID- 28415154
TI - Annona species (Annonaceae): a rich source of potential antitumor agents?
AB - Plants have provided the basis of traditional medicine systems throughout the
world for thousands of years and continue to yield molecules for new remedies. We
analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae),
including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa,
A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here,
we report and discuss the mechanisms of action and structure-activity
relationships of the most active Annona constituents. Annonaceous acetogenins are
one of the most promising classes of natural products, owing to their potential
antitumor activity. However, their neurotoxicity should not be underestimated.
PMID- 28415155
TI - Letter to the Editor regarding Dounousi E et al. Intact FGF23 and alpha-Klotho
during acute inflammation/sepsis in CKD patients.
PMID- 28415157
TI - A Small Case Series of Intravascular Large B-Cell Lymphoma with Unexpected
Findings: Subset of Cases with Concomitant Extravascular Central Nervous System
(CNS) Involvement Mimicking Primary CNS Lymphoma.
AB - BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of
extranodal lymphoma with growth mainly in the lumina of vessels. We studied a
small series of IVLBCL and focused on its central nervous system (CNS)
involvement. METHODS: Searching the medical records of Northwestern Memorial
Hospital, we identified five cases of IVLBCL from January 2007 to January 2015.
Clinical information, hematoxylin and eosin stained histologic slides and
immunohistochemistry studies were reviewed for all cases. Polymerase chain
reaction (PCR) analysis for the immunoglobulin (Ig) heavy and light chain gene
rearrangement was performed on all five cases. RESULTS: Three of the five cases
of IVLBCL were autopsies. Patients' age ranged from 56 to 84. CNS involvement was
present in two cases-in both patients, the CNS involvement showed an
extravascular pattern with confluent sheet-like formation. PCR analysis confirmed
that in one case the systemic intravascular and CNS extravascular components were
clonally identical. CONCLUSIONS: In a small case series of IVLBCL, we observed
that CNS involvement by IVLBCL often has an extravascular morphology, but is
clonally identical to the intravascular counterpart by PCR analysis. As IVLBCL
can have a rapidly progressing poor outcome, it should be kept in the
differential diagnoses for patients presenting with lymphoma of the CNS. The
presence of extravascular growth patterns in the CNS should not exclude IVLBCL as
a diagnosis.
PMID- 28415158
TI - Clinicopathological Study of 18 Cases of Inflammatory Myofibroblastic Tumors with
Reference to ALK-1 Expression: 5-Year Experience in a Tertiary Care Center.
AB - BACKGROUND: Inflammatory myofibroblastic tumor is a histopathologically
distinctive neoplasm of children and young adults. According to World Health
Organization (WHO) classification, inflammatory myofibroblastic tumor is an
intermediate-grade tumor, with potential for recurrence and rare metastasis.
There are no definite histopathologic, molecular, or cytogenetic features to
predict malignant transformation, recurrence, or metastasis. METHODS: A 5-year
retrospective study of histopathologically diagnosed inflammatory myofibroblastic
tumors of various anatomic sites was conducted to correlate anaplastic lymphoma
kinase-1 (ALK-1) expression with histological atypia, multicentric origin of
tumor, recurrence, and metastasis. Clinical details of all the cases were noted
from the clinical work station. Immunohistochemical stains for ALK-1 and other
antibodies were performed. Statistical analysis was done using Fisher exact test.
RESULTS: A total of 18 cases of inflammatory myofibroblastic tumors were found
during the study period, of which 14 were classical. The female-male ratio was
1:1 and the mean age was 23.8 years. Histologically atypical (four cases) and
multifocal tumors (three cases, multicentric in origin) were noted. Recurrence
was noted in 30% of ALK-1 positive and 37.5% of ALK-1 negative cases, whereas
metastasis to the lung, liver, and pelvic bone was noted in the ALK-1 positive
group only. CONCLUSIONS: Overall, ALK-1 protein was expressed in 55.6% of
inflammatory myofibroblastic tumors. There was no statistically significant
correlation between ALK-1 expression, tumor type, recurrence and metastasis.
However, ALK-1 immunohistochemistry is a useful diagnostic aid in the appropriate
clinical and histomorphologic context.
PMID- 28415156
TI - Endocytosis of tight junction proteins and the regulation of degradation and
recycling.
AB - Internalization of tight junction (TJ) proteins from the plasma membrane is a
pivotal mechanism regulating TJ plasticity and function in both epithelial and
endothelial barrier tissues. Once internalized, the TJ proteins enter complex
vesicular machinery, where further trafficking is directly dependent on the
initiating stimulus and downstream signaling pathways that regulate the sorting
and destiny of TJ proteins, as well as on cell and barrier responses. The destiny
of internalized TJ proteins is recycling to the plasma membrane or sorting to
late endosomes and degradation. This review highlights recent advances in our
knowledge of endocytosis and vesicular trafficking of TJ proteins in both
epithelial and endothelial cells. A greater understanding of these processes may
allow for the development of methods to modulate barrier permeability for drug
delivery or prevent barrier dysfunction in disease states.
PMID- 28415159
TI - Comparison of Unsatisfactory Samples from Conventional Smear versus Liquid-Based
Cytology in Uterine Cervical Cancer Screening Test.
AB - BACKGROUND: Cervical cytology for uterine cervical cancer screening has
transitioned from conventional smear (CS) to liquid-based cytology (LBC), which
has many advantages. The aim of this study was to compare the proportion of
unsatisfactory specimens from CS versus LBC at multiple institutions including
general hospitals and commercial laboratories. METHODS: Each participating
institution provided a minimum of 500 Papanicolaou (Pap) test results for
analysis. Pap tests were classified according to the participating institution
(commercial laboratory or general hospital) and the processing method (CS,
ThinPrep, SurePath, or CellPrep). The causes of unsatisfactory results were
classified as technical problems, scant cellularity, or complete obscuring
factors. RESULTS: A total of 38,956 Pap test results from eight general hospitals
and three commercial laboratories were analyzed. The mean unsatisfactory rate of
LBC was significantly lower than that of CS (1.26% and 3.31%, p = .018). In the
LBC method, samples from general hospitals had lower unsatisfactory rates than
those from commercial laboratories (0.65% vs 2.89%, p = .006). The reasons for
unsatisfactory results were heterogeneous in CS. On the other hand, 66.2% of
unsatisfactory results in LBC were due to the scant cellularity. CONCLUSIONS:
Unsatisfactory rate of cervical cancer screening test results varies according to
the institution and the processing method. LBC has a significantly lower
unsatisfactory rate than CS.
PMID- 28415160
TI - A first case of high-flow nasal cannula oxygen therapy in patients with pulmonary
tumor thrombotic microangiopathy.
PMID- 28415161
TI - Lymphoid follicular proctitis resembling rectal carcinoid tumor, confirmed by
endoscopic resection.
PMID- 28415162
TI - Value of Doppler evaluation of physically abnormal fistula: hemodynamic
guidelines and access outcomes.
AB - Background/Aims: The strategy of access care at out center involves the use of
ultrasound (USG) in case of physical examination (PE) abnormality. USG determines
the need of angiography. This study investigated the possible association between
the need for percutaneous transluminal angioplasty (PTA) and hemodynamic
parameters of USG. The study also assessed the effects of this monitoring
strategy on outcomes in comparison with a historical control. Methods: A
retrospective study of the medical records of 127 patients (65 PTA, 62 non-PTA)
was conducted. Data were analyzed using logistic regression analysis and receiver
operating characteristic curve. Fistula outcomes and intervention rates were
calculated and compared with 100 historic controls. Results: Logistic regression
analysis showed that brachial artery flow volume (FV) < 612.9 mL/min or brachial
artery resistance index (RI) > 0.63 was independently associated with the need
for PTA. This monitoring strategy showed an a reduction in thromboses (0.02 +/-
0.11 events/arteriovenous fistula [AVF]-year vs. 0.07 +/- 0.23 events/AVF-year, p
= 0.046), reduction in central venous catheter placement (0.01 +/- 0.05
events/AVF-year vs. 0.06 +/- 0.22 events/AVF-year, p = 0.010), reduction in
access loss (0.02 +/- 0.13 events/AVF-year vs. 0.19 +/- 0.34 events/AVF-year, p =
0.015), and increase in access selective repair (0.49 +/- 0.66 events/AVF-year
vs. 0.21 +/- 0.69 events/AVF-year, p = 0.003), compared to historic control.
Conclusions: There was significant stenosis if brachial artery FV was < 612.9
mL/min or RI was > 0.63 for PE abnormality. These parameters should be used as
markers for assessing PTA risk in hemodialysis patients. Addition of USG to
determine the need of angiography after detection of PE abnormality leads to
decreases in access thrombosis, catheter placement, and access loss despite
increasing access intervention rates compared to clinical monitoring.
PMID- 28415164
TI - Beyond the Classic Segawa Disease, GCH1-Associated Neurodegenerative
Parkinsonism: Practical Considerations for Physicians.
PMID- 28415163
TI - Fragmented QRS and abnormal creatine kinase-MB are predictors of coronary artery
disease in patients with angina and normal electrocardiographys.
AB - BACKGROUND/AIMS: Patients with symptoms of coronary artery disease (CAD) often
display normal tracings or only nonspecific changes on electrocardiography (ECG).
The aim of this study was to explore strategic elements of the ECG and other
potential factors that are predictive of CAD in this scenario. METHODS: This was
an observational study of 142 patients with the chief complaint of chest pain,
each of whom presented with a normal ECG and was subjected to emergency coronary
angiography (CAG). Two population subsets were identified: those patients (n =
97) with no significant stenotic lesions and those (n = 45) with the significant
stenotic lesions of CAD. RESULTS: Those patients with normal or nonspecific ECGs
and CAD (15.8%) were more likely to have left circumflex artery involvement (20%
vs. 7%). In patients with normal ECGs and CAD (vs. normal CAG), male sex (86.7%
vs. 68%, p = 0.023), creatine kinase-MB (CK-MB) levels > 10 U/L (13 vs. 10, p =
0.025), and fragmented QRS (fQRS) (38.6% vs. 21.6%, p = 0.042) occurred with
greater frequency. In multivariable analysis, the following variables were
significant predictors of CAD, given a normal ECG: male sex (odds ratio [OR],
2.593; 95% confidence interval [CI], 1.068 to 5.839); CK-MB (OR, 2.497; 95% CI,
0.955 to 7.039); and W- or M-shaped QRS complex (OR, 2.306; 95% CI 0.988 to
5.382). CONCLUSIONS: In our view, male sex, elevated CK-MB (> 10 U/L), and fQRS
complexes are suspects for CAD in patients with angina and unremarkable ECGs and
should be considered screening tests.
PMID- 28415165
TI - Progressive Supranuclear Gaze Palsy with Predominant Cerebellar Ataxia: A Case
Series with Videos.
AB - Progressive supranuclear palsy (PSP) with predominant cerebellar ataxia (PSP-C)
is a rare phenotype of PSP. The clinical and radiological features of this
disorder remain poorly characterized. Through a retrospective case series, we aim
to characterize the clinical and radiological features of PSP-C. Four patients
with PSP-C were identified: patients who presented with prominent cerebellar
dysfunction that disappeared with the progression of the disease. Supranuclear
gaze palsy occurred at a mean of 2.0 +/- 2.3 years after the onset of ataxia.
Mild cerebellar volume loss and midbrain atrophy were detected on brain imaging,
which are supportive of a diagnosis of PSP. Videos are presented illustrating the
co-existence of cerebellar signs and supranuclear gaze palsy and the
disappearance of cerebellar signs with disease progression. Better recognition
and the development of validated diagnostic criteria would aid in the antemortem
recognition of this rare condition.
PMID- 28415166
TI - Holmes' Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral
Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus.
AB - A 21-year-old male was admitted with severe right arm and hand tremors after a
thalamic hemorrhage caused by a traffic accident. He was also suffering from
agonizing pain in his right shoulder that manifested after the tremor. Neurologic
examination revealed a disabling, severe, and irregular kinetic and postural
tremor in the right arm during target-directed movements. There was also an
irregular ipsilateral rest tremor and dystonic movements in the distal part of
the right arm. The amplitude was moderate at rest and extremely high during
kinetic and intentional movements. The patient underwent left globus pallidum
internus and ventral intermediate thalamic nucleus deep brain stimulation. The
patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating
Scale and Visual Analog Scale six months after surgery.
PMID- 28415167
TI - There Is No Advantage to Transpapillary Pancreatic Duct Stenting for the
Transmural Endoscopic Drainage of Pancreatic Fluid Collections: A Meta-Analysis.
AB - BACKGROUND/AIMS: Options for the endoscopic management of symptomatic pancreatic
fluid collections (PFCs) include transmural drainage (TM) alone, transpapillary
drainage (TP) alone, or a combination of both drainage method (CD). There have
been conflicting reports about the best method. This study performed a meta
analysis to determine whether CD presents an added clinical benefit over TM.
METHODS: The included studies compared TM with CD and reported clinical success
for both methods. A random-effects model was used to determine the pooled odds
ratios (ORs) and the 95% confidence intervals (CIs) for the following outcomes:
technical success, clinical success, complications, and recurrence. RESULTS: Nine
studies involving a combined total of 604 drainage procedures-373 TMs (62%) and
231 CDs (38%)-were included. CD showed no additional benefit over TM in terms of
technical success (OR, 1.12; 95% CI, 0.37-3.37; p=0.85), clinical success (OR,
1.11; 95% CI, 0.65-1.89; p=0.70), recurrence (OR, 1.49; 95% CI, 0.53-4.21;
p=0.45), or complications (OR, 1.15; 95% CI, 0.61-2.18; p=0.67). CONCLUSIONS:
Pancreatic duct (PD) stenting provides no additional clinical benefit for the TM
of PFCs (particularly pseudocysts). Patients undergoing the TM of symptomatic
pseudocysts may not require endoscopic retrograde pancreatography (ERP).
PMID- 28415168
TI - An Update on Endoscopic Management of Post-Liver Transplant Biliary
Complications.
AB - Biliary complications are the most common post-liver transplant (LT)
complications with an incidence of 15%-45%. Furthermore, such complications are
reported more frequently in patients who undergo a living-donor LT compared to a
deceased-donor LT. Most post-LT biliary complications involve biliary strictures,
bile leakage, and biliary stones, although many rarer events, such as hemobilia
and foreign bodies, contribute to a long list of related conditions. Endoscopic
treatment of post-LT biliary complications has evolved rapidly, with new and
effective tools improving both outcomes and success rates; in fact, the latter
now consistently reach up to 80%. In this regard, conventional endoscopic
retrograde cholangiopancreatography remains the preferred initial treatment.
However, percutaneous transhepatic cholangioscopy is now central to the
management of endoscopy-resistant cases involving complex hilar or multiple
strictures with associated stones. Many additional endoscopic tools and
techniques-such as the rendezvous method, magnetic compression anastomosis , and
peroral cholangioscopy-combined with modified biliary stents have significantly
improved the success rate of endoscopic management. Here, we review the current
status of endoscopic treatment of post-LT biliary complications and discuss
conventional as well as the aforementioned new tools and techniques.
PMID- 28415169
TI - Understanding the origin of liquid crystal ordering of ultrashort double-stranded
DNA.
AB - Recent experiments have shown that short double-stranded DNA (dsDNA) fragments
having six- to 20-base pairs exhibit various liquid crystalline phases. This
violates the condition of minimum molecular shape anisotropy that analytical
theories demand for liquid crystalline ordering. It has been hypothesized that
the liquid crystalline ordering is the result of end-to-end stacking of dsDNA to
form long supramolecular columns which satisfy the shape anisotropy criterion
necessary for ordering. To probe the thermodynamic feasibility of this process,
we perform molecular dynamics simulations on ultrashort (four base pair long)
dsDNA fragments, quantify the strong end-to-end attraction between them, and
demonstrate that the nematic ordering of the self-assembled stacked columns is
retained for a large range of temperature and salt concentration.
PMID- 28415170
TI - Variational calculation of transport coefficients in diffusive lattice gases.
AB - A diffusive lattice gas is characterized by the diffusion coefficient depending
only on the density. The Green-Kubo formula for diffusivity can be represented as
a variational formula, but even when the equilibrium properties of a lattice gas
are analytically known, the diffusion coefficient can be computed only in the
exceptional situation when the lattice gas is gradient. In the general case,
minimization over an infinite-dimensional space is required. We propose an
approximation scheme based on minimizing over finite-dimensional subspaces of
functions. The procedure is demonstrated for one-dimensional generalized
exclusion processes in which each site can accommodate at most two particles. Our
analytical predictions provide upper bounds for the diffusivity that are very
close to simulation results throughout the entire density range. We also analyze
nonequilibrium density profiles for finite chains coupled to reservoirs. The
predictions for the profiles are in excellent agreement with simulations.
PMID- 28415171
TI - Acousto-optic effect in random media.
AB - We consider the acousto-optic effect in a random medium. We derive the radiative
transport equations that describe the propagation of multiply scattered light in
a medium whose dielectric permittivity is modulated by an acoustic wave. Using
this result, we present an analysis of the sensitivity of an acousto-optic
measurement to the presence of a small absorbing inhomogeneity.
PMID- 28415172
TI - Averaged model for probabilistic coalescence avalanches in two-dimensional
emulsions: Insights into uncertainty propagation.
AB - A two-dimensional concentrated emulsion exhibits spontaneous rapid
destabilization through an avalanche of coalescence events which propagate
through the assembly stochastically. We propose a deterministic model to explain
the average dynamics of the avalanching process. The dynamics of the avalanche
phenomenon is studied as a function of a composite parameter, the decay time
ratio, which characterizes the ratio of the propensity of coalescence to cease
propagation to that of propagation. When this ratio is small, the avalanche grows
autocatalytically to destabilize the emulsion. Using a scaling analysis, we
unravel the relation between a local characteristic of the system and a global
system wide effect. The anisotropic nature of local coalescence results in a
system size dependent transition from nonautocatalytic to autocatalytic behavior.
By incorporating uncertainty into the parameters in the model, several possible
realizations of the coalescence avalanche are generated. The results are compared
with the Monte Carlo simulations to derive insights into how the uncertainty
propagates in the system.
PMID- 28415173
TI - Signal optimization in urban transport: A totally asymmetric simple exclusion
process with traffic lights.
AB - We consider the exclusion process on a ring with time-dependent defective bonds
at which the hopping rate periodically switches between zero and one. This system
models main roads in city traffics, intersecting with perpendicular streets. We
explore basic properties of the system, in particular dependence of the vehicular
flow on the parameters of signalization as well as the system size and the car
density. We investigate various types of the spatial distribution of the
vehicular density, and show existence of a shock profile. We also measure waiting
time behind traffic lights, and examine its relationship with the traffic flow.
PMID- 28415174
TI - Structure of the optimal path to a fluctuation.
AB - Macroscopic fluctuations have become an essential tool to understand physics far
from equilibrium due to the link between their statistics and nonequilibrium
ensembles. The optimal path leading to a fluctuation encodes key information on
this problem, shedding light on, e.g., the physics behind the enhanced
probability of rare events out of equilibrium, the possibility of dynamic phase
transitions, and new symmetries. This makes the understanding of the properties
of these optimal paths a central issue. Here we derive a fundamental relation
which strongly constrains the architecture of these optimal paths for general d
dimensional nonequilibrium diffusive systems, and implies a nontrivial structure
for the dominant current vector fields. Interestingly, this general relation
(which encompasses and explains previous results) makes manifest the
spatiotemporal nonlocality of the current statistics and the associated optimal
trajectories.
PMID- 28415175
TI - Yielding transitions and grain-size effects in dislocation theory.
AB - The statistical-thermodynamic dislocation theory developed in previous papers is
used here in an analysis of yielding transitions and grain-size effects in
polycrystalline solids. Calculations are based on the 1995 experimental results
of Meyers, Andrade, and Chokshi [Metall. Mater. Trans. A 26, 2881
(1995)MMTAEB1073-562310.1007/BF02669646] for polycrystalline copper under strain
hardening conditions. The main assertion is that the well-known Hall-Petch
effects are caused by enhanced strengths of dislocation sources at the edges of
grains instead of the commonly assumed resistance to dislocation flow across
grain boundaries. The theory describes rapid transitions between elastic and
plastic deformation at yield points; thus it can be used to predict grain-size
dependence of both yield stresses and flow stresses.
PMID- 28415176
TI - Multifractal surrogate-data generation algorithm that preserves pointwise Holder
regularity structure, with initial applications to turbulence.
AB - An algorithm is described that can generate random variants of a time series
while preserving the probability distribution of original values and the
pointwise Holder regularity. Thus, it preserves the multifractal properties of
the data. Our algorithm is similar in principle to well-known algorithms based on
the preservation of the Fourier amplitude spectrum and original values of a time
series. However, it is underpinned by a dual-tree complex wavelet transform
rather than a Fourier transform. Our method, which we term the iterated amplitude
adjusted wavelet transform can be used to generate bootstrapped versions of
multifractal data, and because it preserves the pointwise Holder regularity but
not the local Holder regularity, it can be used to test hypotheses concerning the
presence of oscillating singularities in a time series, an important feature of
turbulence and econophysics data. Because the locations of the data values are
randomized with respect to the multifractal structure, hypotheses about their
mutual coupling can be tested, which is important for the velocity-intermittency
structure of turbulence and self-regulating processes.
PMID- 28415177
TI - Influence of atomic kinetics in the simulation of plasma microscopic properties
and thermal instabilities for radiative bow shock experiments.
AB - Numerical simulations of laboratory astrophysics experiments on plasma flows
require plasma microscopic properties that are obtained by means of an atomic
kinetic model. This fact implies a careful choice of the most suitable model for
the experiment under analysis. Otherwise, the calculations could lead to
inaccurate results and inappropriate conclusions. First, a study of the validity
of the local thermodynamic equilibrium in the calculation of the average
ionization, mean radiative properties, and cooling times of argon plasmas in a
range of plasma conditions of interest in laboratory astrophysics experiments on
radiative shocks is performed in this work. In the second part, we have made an
analysis of the influence of the atomic kinetic model used to calculate plasma
microscopic properties of experiments carried out on magpie on radiative bow
shocks propagating in argon. The models considered were developed assuming both
local and nonlocal thermodynamic equilibrium and, for the latter situation, we
have considered in the kinetic model different effects such as external radiation
field and plasma mixture. The microscopic properties studied were the average
ionization, the charge state distributions, the monochromatic opacities and
emissivities, the Planck mean opacity, and the radiative power loss. The
microscopic study was made as a postprocess of a radiative-hydrodynamic
simulation of the experiment. We have also performed a theoretical analysis of
the influence of these atomic kinetic models in the criteria for the onset
possibility of thermal instabilities due to radiative cooling in those
experiments in which small structures were experimentally observed in the bow
shock that could be due to this kind of instability.
PMID- 28415178
TI - Capillary and geometrically driven fingering instability in nonflat Hele-Shaw
cells.
AB - The usual viscous fingering instability arises when a fluid displaces another of
higher viscosity in a flat Hele-Shaw cell, under sufficiently large capillary
number conditions. In this traditional framing, the reverse flow case (more
viscous fluid displacing a less viscous one) and the viscosity-matched situation
(fluids of equal viscosities) are stable. We revisit this classical fluid dynamic
problem, now considering flow in a nonflat Hele-Shaw cell. For a specific nonflat
environment, we show that both the reverse and the viscosity-matched flows can
become unstable, even at low capillary number. This peculiar fluid fingering
instability is driven by the combined action of capillary effects and geometric
properties of the nonflat Hele-Shaw cell. Our theoretical results indicate that
the Hele-Shaw cell geometry significantly impacts the linear stability and
nonlinear pattern-forming dynamics of the system. This suggests that the geometry
of the medium plays an important role in favoring the occurrence of fingering
patterns in nonflat, confined fluid flows.
PMID- 28415179
TI - Bias cancellation in one-determinant fixed-node diffusion Monte Carlo: Insights
from fermionic occupation numbers.
AB - The accuracy of the fixed-node diffusion Monte Carlo (FNDMC) depends on the node
location of the supplied trial state Psi_{T}. The practical FNDMC approaches
available for large systems rely on compact yet effective Psi_{T}, most often
containing an explicitly correlated single Slater determinant (SD). However, SD
nodes may be better suited to one system than to another, which may possibly lead
to inaccurate FNDMC energy differences. It remains a challenge how to estimate
nonequivalence or appropriateness of SDs. Here we use the differences of a
measure based on the Euclidean distance between the natural orbital occupation
number (NOON) vector of the SD and the exact solution in the NOON vector space,
which can be viewed as a measure of SD nonequivalence and as a qualitative
measure of the expected degree of nondynamic-correlation-related bias in FNDMC
energy differences. This is explored on a set of small noncovalent complexes and
covalent bond breaking of Si_{2} vs N_{2}. It turns out that NOON-based measures
well reflect the magnitude and sign of the bias present in the data available,
thus providing insights into the nature of bias cancellation in SD FNDMC energy
differences.
PMID- 28415181
TI - Universal data-based method for reconstructing complex networks with binary-state
dynamics.
AB - To understand, predict, and control complex networked systems, a prerequisite is
to reconstruct the network structure from observable data. Despite recent
progress in network reconstruction, binary-state dynamics that are ubiquitous in
nature, technology, and society still present an outstanding challenge in this
field. Here we offer a framework for reconstructing complex networks with binary
state dynamics by developing a universal data-based linearization approach that
is applicable to systems with linear, nonlinear, discontinuous, or stochastic
dynamics governed by monotonic functions. The linearization procedure enables us
to convert the network reconstruction into a sparse signal reconstruction problem
that can be resolved through convex optimization. We demonstrate generally high
reconstruction accuracy for a number of complex networks associated with distinct
binary-state dynamics from using binary data contaminated by noise and missing
data. Our framework is completely data driven, efficient, and robust, and does
not require any a priori knowledge about the detailed dynamical process on the
network. The framework represents a general paradigm for reconstructing,
understanding, and exploiting complex networked systems with binary-state
dynamics.
PMID- 28415180
TI - Reversals and collisions optimize protein exchange in bacterial swarms.
AB - Swarming groups of bacteria coordinate their behavior by self-organizing as a
population to move over surfaces in search of nutrients and optimal niches for
colonization. Many open questions remain about the cues used by swarming bacteria
to achieve this self-organization. While chemical cue signaling known as quorum
sensing is well-described, swarming bacteria often act and coordinate on time
scales that could not be achieved via these extracellular quorum sensing cues.
Here, cell-cell contact-dependent protein exchange is explored as a mechanism of
intercellular signaling for the bacterium Myxococcus xanthus. A detailed
biologically calibrated computational model is used to study how M. xanthus
optimizes the connection rate between cells and maximizes the spread of an
extracellular protein within the population. The maximum rate of protein
spreading is observed for cells that reverse direction optimally for swarming.
Cells that reverse too slowly or too fast fail to spread extracellular protein
efficiently. In particular, a specific range of cell reversal frequencies was
observed to maximize the cell-cell connection rate and minimize the time of
protein spreading. Furthermore, our findings suggest that predesigned motion
reversal can be employed to enhance the collective behavior of biological
synthetic active systems.
PMID- 28415182
TI - Sustained turbulence and magnetic energy in nonrotating shear flows.
AB - From numerical simulations, we show that nonrotating magnetohydrodynamic shear
flows are unstable to finite amplitude velocity perturbations and become
turbulent, leading to the growth and sustenance of magnetic energy, including
large scale fields. This supports the concept that sustained magnetic energy from
turbulence is independent of the driving mechanism for large enough magnetic
Reynolds numbers.
PMID- 28415183
TI - Fluctuations in Hertz chains at equilibrium.
AB - We examine the long-term behavior of nonintegrable, energy-conserved, one
dimensional systems of macroscopic grains interacting via a contact-only
generalized Hertz potential and held between stationary walls. Such systems can
be set up to have no phononic background excitation and represent examples of a
sonic vacuum. Existing dynamical studies showed the absence of energy
equipartitioning in such systems, hence their long-term dynamics was described as
quasiequilibrium. Here we show that these systems do in fact reach thermal
equilibrium at sufficiently long times, as indicated by the calculated heat
capacity. As a by-product, we show how fluctuations of system quantities, and
thus the distribution functions, are influenced by the Hertz potential. In
particular, the variance of the system's kinetic energy probability density
function is reduced by a factor related to the contact potential.
PMID- 28415184
TI - Multiscale structure of time series revealed by the monotony spectrum.
AB - Observation of complex systems produces time series with specific dynamics at
different time scales. The majority of the existing numerical methods for
multiscale analysis first decompose the time series into several simpler
components and the multiscale structure is given by the properties of their
components. We present a numerical method which describes the multiscale
structure of arbitrary time series without decomposing them. It is based on the
monotony spectrum defined as the variation of the mean amplitude of the monotonic
segments with respect to the mean local time scale during successive averagings
of the time series, the local time scales being the durations of the monotonic
segments. The maxima of the monotony spectrum indicate the time scales which
dominate the variations of the time series. We show that the monotony spectrum
can correctly analyze a diversity of artificial time series and can discriminate
the existence of deterministic variations at large time scales from the random
fluctuations. As an application we analyze the multifractal structure of some
hydrological time series.
PMID- 28415185
TI - Passive scalars: Mixing, diffusion, and intermittency in helical and nonhelical
rotating turbulence.
AB - We use direct numerical simulations to compute structure functions, scaling
exponents, probability density functions, and effective transport coefficients of
passive scalars in turbulent rotating helical and nonhelical flows. We show that
helicity affects the inertial range scaling of the velocity and of the passive
scalar when rotation is present, with a spectral law consistent with ~k_{?}^{
1.4} for the passive scalar variance spectrum. This scaling law is consistent
with a phenomenological argument [P. Rodriguez Imazio and P. D. Mininni, Phys.
Rev. E 83, 066309 (2011)PLEEE81539-375510.1103/PhysRevE.83.066309] for rotating
nonhelical flows, which follows directly from Kolmogorov-Obukhov scaling and
states that if energy follows a E(k)~k^{-n} law, then the passive scalar variance
follows a law V(k)~k^{-n_{theta}} with n_{theta}=(5-n)/2. With the second-order
scaling exponent obtained from this law, and using the Kraichnan model, we obtain
anomalous scaling exponents for the passive scalar that are in good agreement
with the numerical results. Multifractal intermittency models are also
considered. Intermittency of the passive scalar is stronger than in the
nonhelical rotating case, a result that is also confirmed by stronger non
Gaussian tails in the probability density functions of field increments. Finally,
Fick's law is used to compute the effective diffusion coefficients in the
directions parallel and perpendicular to rotation. Calculations indicate that
horizontal diffusion decreases in the presence of helicity in rotating flows,
while vertical diffusion increases. A simple mean field argument explains this
behavior in terms of the amplitude of velocity fluctuations.
PMID- 28415186
TI - Scaling of slip avalanches in sheared amorphous materials based on large-scale
atomistic simulations.
AB - Atomistic simulations of binary amorphous systems with over 4 million atoms are
performed. Systems of two interatomic potentials of the Lennard-Jones type, LJ12
6 and LJ9-6, are simulated. The athermal quasistatic shearing protocol is
adopted, where the shear strain is applied in a stepwise fashion with each step
followed by energy minimization. For each avalanche event, the shear stress drop
(Deltasigma), the hydrostatic pressure drop (Deltasigma_{h}), and the potential
energy drop (DeltaE) are computed. It is found that, with the avalanche size
increasing, the three become proportional to each other asymptotically. The
probability distributions of avalanche sizes are obtained and values of scaling
exponents fitted. In particular, the distributions follow a power law,
P(DeltaU)~DeltaU^{-tau}, where DeltaU is a measure of avalanche sizes defined
based on shear stress drops. The exponent tau is 1.25+/-0.1 for the LJ12-6
systems, and 1.15+/-0.1 for the LJ9-6 systems. The value of tau for the LJ12-6
systems is consistent with that from an earlier atomistic simulation study by
Robbins et al. [Phys. Rev. Lett. 109, 105703 (2012)]PRLTAO0031
900710.1103/PhysRevLett.109.105703, but the fitted values of other scaling
exponents differ, which may be because the shearing protocol used here differs
from that in their study.
PMID- 28415187
TI - Poverty index with time-varying consumption and income distributions.
AB - Starting from a stochastic agent-based model to represent market exchange in a
developing economy, we study time variations of the probability density function
of income with simultaneous variation of the consumption deprivation (CD), where
CD represents the shortfall in consumption from the saturation level of an
essential commodity, cereal. Together, these two models combine income
expenditure-based market dynamics with time variations in consumption due to
income. In this new unified theoretical structure, exchange of trade in assets is
only allowed when the income exceeds consumption-deprivation while CD itself is
endogenously obtained from a separate kinetic model. Our results reveal that the
nature of time variation of the CD function leads to a downward trend in the
threshold level of consumption of basic necessities, suggesting a possible
dietary transition in terms of lower saturation level of food-grain consumption,
possibly through an improvement in the level of living. The new poverty index,
defined as CD, is amenable to approximate probabilistic prediction within a short
time horizon. A major achievement of this work is the intrinsic independence of
the poverty index from an exogenous poverty line, making it more objective for
policy formulation as opposed to existing poverty indices in the literature.
PMID- 28415188
TI - Universality classes of fluctuation dynamics in hierarchical complex systems.
AB - A unified approach is proposed to describe the statistics of the short-time
dynamics of multiscale complex systems. The probability density function of the
relevant time series (signal) is represented as a statistical superposition of a
large time-scale distribution weighted by the distribution of certain internal
variables that characterize the slowly changing background. The dynamics of the
background is formulated as a hierarchical stochastic model whose form is derived
from simple physical constraints, which in turn restrict the dynamics to only two
possible classes. The probability distributions of both the signal and the
background have simple representations in terms of Meijer G functions. The two
universality classes for the background dynamics manifest themselves in the
signal distribution as two types of tails: power law and stretched exponential,
respectively. A detailed analysis of empirical data from classical turbulence and
financial markets shows excellent agreement with the theory.
PMID- 28415189
TI - Slip and barodiffusion phenomena in slow flows of a gas mixture.
AB - The slip and barodiffusion problems for the slow flows of a gas mixture are
investigated on the basis of the linearized moment equations following from the
Boltzmann equation. We restrict ourselves to the set of the third-order moment
equations and state two general relations (resembling conservation equations) for
the moments of the distribution function similar to the conditions used by
Loyalka [S. K. Loyalka, Phys. Fluids 14, 2291 (1971)10.1063/1.1693331] in his
approximation method (the modified Maxwell method). The expressions for the
macroscopic velocities of the gas mixture species, the partial viscous stress
tensors, and the reduced heat fluxes for the stationary slow flow of a gas
mixture in the semi-infinite space over a plane wall are obtained as a result of
the exact solution of the linearized moment equations in the 10- and 13-moment
approximations. The general expression for the slip velocity and the simple and
accurate expressions for the viscous, thermal, diffusion slip, and baroslip
coefficients, which are given in terms of the basic transport coefficients, are
derived by using the modified Maxwell method. The solutions of moment equations
are also used for investigation of the flow and diffusion of a gas mixture in a
channel formed by two infinite parallel plates. A fundamental result is that the
barodiffusion factor in the cross-section-averaged expression for the diffusion
flux contains contributions associated with the viscous transfer of momentum in
the gas mixture and the effect of the Knudsen layer. Our study revealed that the
barodiffusion factor is equal to the diffusion slip coefficient (correct to the
opposite sign). This result is consistent with the Onsager's reciprocity
relations for kinetic coefficients following from nonequilibrium thermodynamics
of the discontinuous systems.
PMID- 28415190
TI - Density-functional calculations of transport properties in the nondegenerate
limit and the role of electron-electron scattering.
AB - We compute electrical and thermal conductivities of hydrogen plasmas in the
nondegenerate regime using Kohn-Sham density functional theory (DFT) and an
application of the Kubo-Greenwood response formula, and demonstrate that for
thermal conductivity, the mean-field treatment of the electron-electron (e-e)
interaction therein is insufficient to reproduce the weak-coupling limit obtained
by plasma kinetic theories. An explicit e-e scattering correction to the DFT is
posited by appealing to Matthiessen's Rule and the results of our computations of
conductivities with the quantum Lenard-Balescu (QLB) equation. Further motivation
of our correction is provided by an argument arising from the Zubarev quantum
kinetic theory approach. Significant emphasis is placed on our efforts to produce
properly converged results for plasma transport using Kohn-Sham DFT, so that an
accurate assessment of the importance and efficacy of our e-e scattering
corrections to the thermal conductivity can be made.
PMID- 28415191
TI - Random walk in nonhomogeneous environments: A possible approach to human and
animal mobility.
AB - The random walk process in a nonhomogeneous medium, characterized by a Levy
stable distribution of jump length, is discussed. The width depends on a
position: either before the jump or after that. In the latter case, the density
slope is affected by the variable width and the variance may be finite; then all
kinds of the anomalous diffusion are predicted. In the former case, only the time
characteristics are sensitive to the variable width. The corresponding Langevin
equation with different interpretations of the multiplicative noise is discussed.
The dependence of the distribution width on position after jump is interpreted in
terms of cognitive abilities and related to such problems as migration in a human
population and foraging habits of animals.
PMID- 28415192
TI - Multiple-node basin stability in complex dynamical networks.
AB - Dynamical entities interacting with each other on complex networks often exhibit
multistability. The stability of a desired steady regime (e.g., a synchronized
state) to large perturbations is critical in the operation of many real-world
networked dynamical systems such as ecosystems, power grids, the human brain,
etc. This necessitates the development of appropriate quantifiers of stability of
multiple stable states of such systems. Motivated by the concept of basin
stability (BS) [P. J. Menck et al., Nat. Phys. 9, 89 (2013)1745
247310.1038/nphys2516], we propose here the general framework of multiple-node
basin stability for gauging the global stability and robustness of networked
dynamical systems in response to nonlocal perturbations simultaneously affecting
multiple nodes of a system. The framework of multiple-node BS provides an
estimate of the critical number of nodes that, when simultaneously perturbed,
significantly reduce the capacity of the system to return to the desired stable
state. Further, this methodology can be applied to estimate the minimum number of
nodes of the network to be controlled or safeguarded from external perturbations
to ensure proper operation of the system. Multiple-node BS can also be utilized
for probing the influence of spatially localized perturbations or targeted
attacks to specific parts of a network. We demonstrate the potential of multiple
node BS in assessing the stability of the synchronized state in a deterministic
scale-free network of Rossler oscillators and a conceptual model of the power
grid of the United Kingdom with second-order Kuramoto-type nodal dynamics.
PMID- 28415193
TI - Minimum memory for generating rare events.
AB - We classify the rare events of structured, memoryful stochastic processes and use
this to analyze sequential and parallel generators for these events. Given a
stochastic process, we introduce a method to construct a process whose typical
realizations are a given process' rare events. This leads to an expression for
the minimum memory required to generate rare events. We then show that the
recently discovered classical-quantum ambiguity of simplicity also occurs when
comparing the structure of process fluctuations.
PMID- 28415194
TI - Migration of a droplet in a cylindrical tube in the creeping flow regime.
AB - The migration of a neutrally buoyant droplet in a tube containing another
immiscible liquid is investigated numerically in the creeping flow regime. A
fully developed velocity profile is imposed at the inlet of the tube. The
interface between the two immiscible fluids is captured using a coupled level-set
and volume-of-fluid approach. The deformation and breakup dynamics of the droplet
are investigated in terms of three dimensionless parameters, namely, the ratio
between the radius of the undeformed droplet and the radius of the capillary
tube, the viscosity ratio between the dispersed and the continuous phases, and
the capillary number that measures the relative importance of the viscous force
over the surface tension force. It has been observed that the droplet, while
traversing through the tube, either approaches a steady bulletlike shape or
develops a prominent reentrant cavity at its rear. Depending on the initial
droplet size, there exists a critical capillary number for every flow
configuration beyond which the drop fails to maintain a steady shape and breaks
into fragments. The deformation and breakup phenomena depend primarily on the
droplet size, the viscosity ratio, and the capillary number. Special attention
has been given to the case where the drop diameter is comparable with the tube
diameter. A thorough computational study has been conducted to find the critical
capillary number for a range of droplets of varied sizes suspended in systems
having different viscosity ratios.
PMID- 28415195
TI - Ultrafast probing of magnetic field growth inside a laser-driven solenoid.
AB - We report on the detection of the time-dependent B-field amplitude and topology
in a laser-driven solenoid. The B-field inferred from both proton deflectometry
and Faraday rotation ramps up linearly in time reaching 210 +/- 35 T at the end
of a 0.75-ns laser drive with 1 TW at 351 nm. A lumped-element circuit model
agrees well with the linear rise and suggests that the blow-off plasma screens
the field between the plates leading to an increased plate capacitance that
converts the laser-generated hot-electron current into a voltage source that
drives current through the solenoid. ALE3D modeling shows that target disassembly
and current diffusion may limit the B-field increase for longer laser drive.
Scaling of these experimental results to a National Ignition Facility (NIF)
hohlraum target size (~0.2cm^{3}) indicates that it is possible to achieve
several tens of Tesla.
PMID- 28415196
TI - Traffic gridlock on a honeycomb city.
AB - Inspired by an old and almost in oblivion urban plan, we report the behavior of
the Biham-Middleton-Levine (BML) model-a paradigm for studying phase transitions
of traffic flow-on a hypothetical city with a perfect honeycomb street network.
In contrast with the original BML model on a square lattice, the same model on a
honeycomb does not show any anisotropy or intermediate states, but a single
continuous phase transition between free and totally congested flow, a transition
that can be completely characterized by the tools of classical percolation.
Although the transition occurs at a lower density than for the conventional BML,
simple modifications, like randomly stopping the cars with a very small
probability or increasing the traffic light periods, drives the model to perform
better on honeycomb lattices. As traffic lights and disordered perturbations are
inherent in real traffic, these results question the actual role of the square
gridlike designs and suggest the honeycomb topology as an interesting alternative
for urban planning in real cities.
PMID- 28415197
TI - Quantum walks: The first detected passage time problem.
AB - Even after decades of research, the problem of first passage time statistics for
quantum dynamics remains a challenging topic of fundamental and practical
importance. Using a projective measurement approach, with a sampling time tau, we
obtain the statistics of first detection events for quantum dynamics on a
lattice, with the detector located at the origin. A quantum renewal equation for
a first detection wave function, in terms of which the first detection
probability can be calculated, is derived. This formula gives the relation
between first detection statistics and the solution of the corresponding
Schrodinger equation in the absence of measurement. We illustrate our results
with tight-binding quantum walk models. We examine a closed system, i.e., a ring,
and reveal the intricate influence of the sampling time tau on the statistics of
detection, discussing the quantum Zeno effect, half dark states, revivals, and
optimal detection. The initial condition modifies the statistics of a quantum
walk on a finite ring in surprising ways. In some cases, the average detection
time is independent of the sampling time while in others the average exhibits
multiple divergences as the sampling time is modified. For an unbounded one
dimensional quantum walk, the probability of first detection decays like
(time)^{(-3)} with superimposed oscillations, with exceptional behavior when the
sampling period tau times the tunneling rate gamma is a multiple of pi/2. The
amplitude of the power-law decay is suppressed as tau->0 due to the Zeno effect.
Our work, an extended version of our previously published paper, predicts rich
physical behaviors compared with classical Brownian motion, for which the first
passage probability density decays monotonically like (time)^{-3/2}, as
elucidated by Schrodinger in 1915.
PMID- 28415198
TI - Recommender engine for continuous-time quantum Monte Carlo methods.
AB - Recommender systems play an essential role in the modern business world. They
recommend favorable items such as books, movies, and search queries to users
based on their past preferences. Applying similar ideas and techniques to Monte
Carlo simulations of physical systems boosts their efficiency without sacrificing
accuracy. Exploiting the quantum to classical mapping inherent in the continuous
time quantum Monte Carlo methods, we construct a classical molecular gas model to
reproduce the quantum distributions. We then utilize powerful molecular
simulation techniques to propose efficient quantum Monte Carlo updates. The
recommender engine approach provides a general way to speed up the quantum
impurity solvers.
PMID- 28415199
TI - Identifying polymer states by machine learning.
AB - The ability of a feed-forward neural network to learn and classify different
states of polymer configurations is systematically explored. Performing numerical
experiments, we find that a simple network model can, after adequate training,
recognize multiple structures, including gaslike coil, liquidlike globular, and
crystalline anti-Mackay and Mackay structures. The network can be trained to
identify the transition points between various states, which compare well with
those identified by independent specific-heat calculations. Our study
demonstrates that neural networks provide an unconventional tool to study the
phase transitions in polymeric systems.
PMID- 28415200
TI - Triangles bridge the scales: Quantifying cellular contributions to tissue
deformation.
AB - In this article, we propose a general framework to study the dynamics and
topology of cellular networks that capture the geometry of cell packings in two
dimensional tissues. Such epithelia undergo large-scale deformation during
morphogenesis of a multicellular organism. Large-scale deformations emerge from
many individual cellular events such as cell shape changes, cell rearrangements,
cell divisions, and cell extrusions. Using a triangle-based representation of
cellular network geometry, we obtain an exact decomposition of large-scale
material deformation. Interestingly, our approach reveals contributions of
correlations between cellular rotations and elongation as well as cellular growth
and elongation to tissue deformation. Using this triangle method, we discuss
tissue remodeling in the developing pupal wing of the fly Drosophila
melanogaster.
PMID- 28415201
TI - Self-adjustment and disintegration threshold of Langmuir solitons in
inhomogeneous plasmas.
AB - Dynamics of Langmuir solitons in the presence of a background density gradient is
investigated numerically, including cases with steep gradients to the extent the
solitons can disintegrate. The disintegration threshold is explained by regarding
the electric field part of the soliton as a point mass moving along the self
generated potential well corresponding to the density cavity. On the other hand,
it is demonstrated that the Langmuir solitons are robust when the density
gradient is below the threshold. During the acceleration phase toward low density
regions, Langmuir solitons adjust themselves to balance the electric field
pressure and the negative plasma pressure by expelling the imbalanced portion as
density cavities at the sound velocity. When the density gradient is below the
disintegration threshold, the electric field part of the soliton bounces back and
forth within the potential well suggesting the solitons have internal structures.
PMID- 28415202
TI - Efficient approach to the free energy of crystals via Monte Carlo simulations:
Application to continuous and orientation-dependent potentials.
AB - We extend a recently proposed approach to determine the absolute free energy of
crystalline phases [Phys. Rev. E 92, 022103 (2015)PLEEE81539
375510.1103/PhysRevE.92.022103] to systems with continuous and orientation
dependent potentials. The method is based on the Monte Carlo thermodynamic
integration method, and it provides a general procedure to obtain a simple,
analytical, and exact reference free energy, together with an easy and accurate
thermodynamic coupling integral. The approach is free from the difficulties of
the standard method based on the harmonic coupling potential. A comparative
discussion of both approaches is provided.
PMID- 28415203
TI - Transfer entropy in continuous time, with applications to jump and neural spiking
processes.
AB - Transfer entropy has been used to quantify the directed flow of information
between source and target variables in many complex systems. While transfer
entropy was originally formulated in discrete time, in this paper we provide a
framework for considering transfer entropy in continuous time systems, based on
Radon-Nikodym derivatives between measures of complete path realizations. To
describe the information dynamics of individual path realizations, we introduce
the pathwise transfer entropy, the expectation of which is the transfer entropy
accumulated over a finite time interval. We demonstrate that this formalism
permits an instantaneous transfer entropy rate. These properties are analogous to
the behavior of physical quantities defined along paths such as work and heat. We
use this approach to produce an explicit form for the transfer entropy for pure
jump processes, and highlight the simplified form in the specific case of point
processes (frequently used in neuroscience to model neural spike trains).
Finally, we present two synthetic spiking neuron model examples to exhibit the
pertinent features of our formalism, namely, that the information flow for point
processes consists of discontinuous jump contributions (at spikes in the target)
interrupting a continuously varying contribution (relating to waiting times
between target spikes). Numerical schemes based on our formalism promise
significant benefits over existing strategies based on discrete time formalisms.
PMID- 28415204
TI - Dramatic effect of fluid chemistry on cornstarch suspensions: Linking particle
interactions to macroscopic rheology.
AB - Suspensions of cornstarch in water exhibit strong dynamic shear thickening. We
show that partly replacing water with ethanol strongly alters the suspension
rheology. We perform steady and nonsteady rheology measurements combined with
atomic force microscopy to investigate the role of fluid chemistry on the
macroscopic rheology of the suspensions and its link with the interactions
between cornstarch grains. Upon increasing the ethanol content, the suspension
goes through a yield-stress fluid state and ultimately becomes a shear-thinning
fluid. On the cornstarch grain scale, atomic force microscopy measurements reveal
the presence of polymers on the cornstarch surface, which exhibit a cosolvency
effect. At intermediate ethanol content, a maximum of polymer solubility induces
high microscopic adhesion which we relate to the macroscopic yield stress.
PMID- 28415205
TI - Cross-symmetric dipolar-matter-wave solitons in double-well chains.
AB - We consider a dipolar Bose-Einstein condensate trapped in an array of two-well
systems with an arbitrary orientation of the dipoles relative to the system's
axis. The system can be built as a chain of local traps sliced into two parallel
lattices by a repelling laser sheet. It is modeled by a pair of coupled discrete
Gross-Pitaevskii equations, with dipole-dipole self-interactions and cross
interactions. When the dipoles are not polarized perpendicular or parallel to the
lattice, the cross interaction is asymmetric, replacing the familiar symmetric
two-component discrete solitons by two new species of cross-symmetric ones, viz.,
on-site- and off-site-centered solitons, which are strongly affected by the
orientation of the dipoles and separation between the parallel lattices. A very
narrow region of intermediate asymmetric discrete solitons is found at the
boundary between the on- and off-site families. Two different types of solitons
in the PT-symmetric version of the system are constructed too, and stability
areas are identified for them.
PMID- 28415206
TI - Chimera patterns in two-dimensional networks of coupled neurons.
AB - We discuss synchronization patterns in networks of FitzHugh-Nagumo and leaky
integrate-and-fire oscillators coupled in a two-dimensional toroidal geometry. A
common feature between the two models is the presence of fast and slow dynamics,
a typical characteristic of neurons. Earlier studies have demonstrated that both
models when coupled nonlocally in one-dimensional ring networks produce chimera
states for a large range of parameter values. In this study, we give evidence of
a plethora of two-dimensional chimera patterns of various shapes, including
spots, rings, stripes, and grids, observed in both models, as well as additional
patterns found mainly in the FitzHugh-Nagumo system. Both systems exhibit
multistability: For the same parameter values, different initial conditions give
rise to different dynamical states. Transitions occur between various patterns
when the parameters (coupling range, coupling strength, refractory period, and
coupling phase) are varied. Many patterns observed in the two models follow
similar rules. For example, the diameter of the rings grows linearly with the
coupling radius.
PMID- 28415208
TI - X-ray shadow imprint of hydrodynamic instabilities on the surface of inertial
confinement fusion capsules by the fuel fill tube.
AB - Measurements of hydrodynamic instability growth for a high-density carbon ablator
for indirectly driven inertial confinement fusion implosions on the National
Ignition Facility are reported. We observe significant unexpected features on the
capsule surface created by shadows of the capsule fill tube, as illuminated by
laser-irradiated x-ray spots on the hohlraum wall. These shadows increase the
spatial size and shape of the fill tube perturbation in a way that can
significantly degrade performance in layered implosions compared to previous
expectations. The measurements were performed at a convergence ratio of ~2 using
in-flight x-ray radiography. The initial seed due to shadow imprint is estimated
to be equivalent to ~50-100 nm of solid ablator material. This discovery has
prompted the need for a mitigation strategy for future inertial confinement
fusion designs as proposed here.
PMID- 28415207
TI - Model of polar auxin transport coupled to mechanical forces retrieves robust
morphogenesis along the Arabidopsis root.
AB - Stem cells are identical in many scales, they share the same molecular
composition, DNA, genes, and genetic networks, yet they should acquire different
properties to form a functional tissue. Therefore, they must interact and get
some external information from their environment, either spatial (dynamical
fields) or temporal (lineage). In this paper we test to what extent coupled
chemical and physical fields can underlie the cell's positional information
during development. We choose the root apical meristem of Arabidopsis thaliana to
model the emergence of cellular patterns. We built a model to study the dynamics
and interactions between the cell divisions, the local auxin concentration, and
physical elastic fields. Our model recovers important aspects of the self
organized and resilient behavior of the observed cellular patterns in the
Arabidopsis root, in particular, the reverse fountain pattern observed in the
auxin transport, the PIN-FORMED (protein family of auxin transporters)
polarization pattern and the accumulation of auxin near the region of maximum
curvature in a bent root. Our model may be extended to predict altered cellular
patterns that are expected under various applied auxin treatments or modified
physical growth conditions.
PMID- 28415209
TI - Onset of anomalous diffusion in colloids confined to quasimonolayers.
AB - It has been recently shown that a colloidal monolayer, e.g., formed at a fluid
interface or by means of a suitable confining potential, exhibits anomalous
collective diffusion. This is a consequence of the hydrodynamic interactions
mediated by the three-dimensional (3D) ambient fluid when the particles are
confined to reside on a two-dimensional (2D) manifold. We study theoretically and
with numerical simulations the crossover from normal to anomalous diffusion as
the particles are, in real systems, confined by a 3D external potential and thus
have the possibility to fluctuate out of the 2D manifold, thus forming a
quasimonolayer.
PMID- 28415210
TI - Ultraslow diffusion and weak ergodicity breaking in right triangular billiards.
AB - We investigate the diffusion behavior of a right triangular billiard system by
transforming its dynamics to a two-dimensional piecewise map. We find that the
diffusion in the momentum space is ultraslow, i.e., the mean squared displacement
grows asymptotically as the square of the logarithm of time. The mechanism of the
ultraslow diffusion behavior is explained and numerical evidence corroborating
our conclusion is provided. The weak ergodicity breaking of the system is also
discussed.
PMID- 28415211
TI - Dynamics of vortex-antivortex pairs and rarefaction pulses in liquid light.
AB - We present a numerical study of the cubic-quintic nonlinear Schrodinger equation
in two transverse dimensions, relevant for the propagation of light in certain
exotic media. A well-known feature of the model is the existence of flat-top
bright solitons of fixed intensity, whose dynamics resembles the physics of a
liquid. They support traveling wave solutions, consisting of rarefaction pulses
and vortex-antivortex pairs. In this work, we demonstrate how the vortex
antivortex pairs can be generated in bright soliton collisions displaying
destructive interference followed by a snake instability. We then discuss the
collisional dynamics of the dark excitations for different initial conditions. We
describe a number of distinct phenomena including vortex exchange modes,
quasielastic flyby scattering, solitonlike crossing, fully inelastic collisions,
and rarefaction pulse merging.
PMID- 28415213
TI - Non-Gaussian limit fluctuations in active swimmer suspensions.
AB - We investigate the hydrodynamic fluctuations in suspensions of swimming
microorganisms (Chlamydomonas) by observing the probe particles dispersed in the
media. Short-term fluctuations of probe particles were superdiffusive and
displayed heavily tailed non-Gaussian distributions. The analytical theory that
explains the observed distribution was derived by summing the power-law-decaying
hydrodynamic interactions from spatially distributed field sources (here,
swimming microorganisms). The summing procedure, which we refer to as the
physical limit operation, is applicable to a variety of physical fluctuations to
which the classical central limiting theory does not apply. Extending the
analytical formula to compare to experiments in active swimmer suspensions, we
show that the non-Gaussian shape of the observed distribution obeys the analytic
theory concomitantly with independently determined parameters such as the
strength of force generations and the concentration of Chlamydomonas. Time
evolution of the distributions collapsed to a single master curve, except for
their extreme tails, for which our theory presents a qualitative explanation.
Investigations thereof and the complete agreement with theoretical predictions
revealed broad applicability of the formula to dispersions of active sources of
fluctuations.
PMID- 28415212
TI - Scaling laws of reflection coefficients of quantum waves at a Cantor-like
potential.
AB - We reconsider a one-dimensional scattering problem in the Schrodinger equation
with a Cantor-like potential. The reflection coefficient obeys a scaling law for
sufficiently large wave number k. The scaling law is expressed with a universal
function characterized by a multifractal.
PMID- 28415214
TI - Stochastic thermodynamics for Ising chain and symmetric exclusion process.
AB - We verify the finite-time fluctuation theorem for a linear Ising chain in contact
with heat reservoirs at its ends. Analytic results are derived for a chain
consisting of two spins. The system can be mapped onto a model for particle
transport, namely, the symmetric exclusion process in contact with thermal and
particle reservoirs. We modify the symmetric exclusion process to represent a
thermal engine and reproduce universal features of the efficiency at maximum
power.
PMID- 28415215
TI - Levy flight with absorption: A model for diffusing diffusivity with long tails.
AB - We consider diffusion of a particle in rearranging environment, so that the
diffusivity of the particle is a stochastic function of time. In our previous
model of "diffusing diffusivity" [Jain and Sebastian, J. Phys. Chem. B 120, 3988
(2016)JPCBFK1520-610610.1021/acs.jpcb.6b01527], it was shown that the mean square
displacement of particle remains Fickian, i.e., ?T at all times, but
the probability distribution of particle displacement is not Gaussian at all
times. It is exponential at short times and crosses over to become Gaussian only
in a large time limit in the case where the distribution of D in that model has a
steady state limit which is exponential, i.e., pi_{e}(D)~e^{-D/D_{0}}. In the
present study, we model the diffusivity of a particle as a Levy flight process so
that D has a power-law tailed distribution, viz., pi_{e}(D)~D^{-1-alpha} with
0 is slow. Such process is characterized by the power-law growth of
the largest possible observable value of N at a given time t. We find similar
features also for the reverse process of the regression from a rare state with
N? to a typical one with N?.
PMID- 28415227
TI - Fluctuation loops in noise-driven linear dynamical systems.
AB - Understanding the spatiotemporal structure of most probable fluctuation pathways
to rarely occurring states is a central problem in the study of noise-driven,
nonequilibrium dynamical systems. When the underlying system does not possess
detailed balance, the optimal fluctuation pathway to a particular state and
relaxation pathway from that state may combine to form a looplike structure in
the system phase space called a fluctuation loop. Here, fluctuation loops are
studied in a linear circuit model consisting of coupled RC elements, where each
element is driven by its own independent noise source. Using a stochastic
Hamiltonian approach, we determine the optimal fluctuation pathways, and
analytically construct corresponding fluctuation loops. To quantitatively
characterize fluctuation loops, we study the time-dependent area tensor that is
swept out by individual stochastic trajectories in the system phase space. At
long times, the area tensor scales linearly with time, with a coefficient that
precisely vanishes when the system satisfies detailed balance.
PMID- 28415229
TI - Phase behavior and characterization of heptamethyltrisiloxane-based de Vries
smectic liquid crystal by electro-optics, x rays, and dielectric spectroscopy.
AB - A heptamethyltrisiloxane liquid crystal (LC) exhibiting I-SmA^{*}-SmC^{*} phases
has been characterized by calorimetry, polarizing microscopy, x-ray diffraction,
electro-optics, and dielectric spectroscopy. Observations of a large
electroclinic effect, a large increase in the birefringence (Deltan) with
electric field, a low shrinkage in the layer thickness (~1.75%) at 20 degrees C
below the SmA^{*}-SmC^{*} transition, and low values of the reduction factor
(~0.40) suggest that the SmA^{*} phase in this material is of the de Vries type.
The reduction factor is a measure of the layer shrinkage in the SmC^{*} phase and
it should be zero for an ideal de Vries. Moreover, a decrease in the magnitude of
Deltan with decreasing temperature indicates the presence of the temperature
dependent tilt angle in the SmA^{*} phase. The electro-optic behavior is
explained by the generalized Langevin-Debye model as given by Shen et al. [Y.
Shen et al., Phys. Rev. E 88, 062504 (2013)10.1103/PhysRevE.88.062504]. The soft
mode dielectric relaxation strength shows a critical behavior when the system
goes from the SmA^{*} to the SmC^{*} phase.
PMID- 28415230
TI - Scale-invariant puddles in graphene: Geometric properties of electron-hole
distribution at the Dirac point.
AB - We characterize the carrier density profile of the ground state of graphene in
the presence of particle-particle interaction and random charged impurity in zero
gate voltage. We provide detailed analysis on the resulting spatially
inhomogeneous electron gas, taking into account the particle-particle interaction
and the remote Coulomb disorder on an equal footing within the Thomas-Fermi-Dirac
theory. We present some general features of the carrier density probability
measure of the graphene sheet. We also show that, when viewed as a random
surface, the electron-hole puddles at zero chemical potential show peculiar self
similar statistical properties. Although the disorder potential is chosen to be
Gaussian, we show that the charge field is non-Gaussian with unusual Kondev
relations, which can be regarded as a new class of two-dimensional random-field
surfaces. Using Schramm-Loewner (SLE) evolution, we numerically demonstrate that
the ungated graphene has conformal invariance and the random zero-charge density
contours are SLE_{kappa} with kappa=1.8+/-0.2, consistent with c=-3 conformal
field theory.
PMID- 28415231
TI - Gap solitons in Rabi lattices.
AB - We introduce a two-component one-dimensional system, which is based on two
nonlinear Schrodinger or Gross-Pitaevskii equations (GPEs) with spatially
periodic modulation of linear coupling ("Rabi lattice") and self-repulsive
nonlinearity. The system may be realized in a binary Bose-Einstein condensate,
whose components are resonantly coupled by a standing optical wave, as well as in
terms of the bimodal light propagation in periodically twisted waveguides. The
system supports various types of gap solitons (GSs), which are constructed, and
their stability is investigated, in the first two finite bandgaps of the
underlying spectrum. These include on- and off-site-centered solitons (the GSs of
the off-site type are additionally categorized as spatially even and odd ones),
which may be symmetric or antisymmetric, with respect to the coupled components.
The GSs are chiefly stable in the first finite bandgap and unstable in the second
one. In addition to that, there are narrow regions near the right edge of the
first bandgap, and in the second one, which feature intricate alternation of
stability and instability. Unstable solitons evolve into robust breathers or
spatially confined turbulent modes. On-site-centered GSs are also considered in a
version of the system that is made asymmetric by the Zeeman effect, or by
birefringence of the optical waveguide. A region of alternate stability is found
in the latter case too. In the limit of strong asymmetry, GSs are obtained in a
semianalytical approximation, which reduces two coupled GPEs to a single one with
an effective lattice potential.
PMID- 28415232
TI - Certain bright soliton interactions of the Sasa-Satsuma equation in a monomode
optical fiber.
AB - Under investigation in this paper is the Sasa-Satsuma equation, which describes
the propagation of ultrashort pulses in a monomode fiber with the third-order
dispersion, self-steepening, and stimulated Raman scattering effects. Based on
the known bilinear forms, through the modified expanded formulas and symbolic
computation, we construct the bright two-soliton solutions. Through classifying
the interactions under different parameter conditions, we reveal six cases of
interactions between the two solitons via an asymptotic analysis. With the help
of the analytic and graphic analysis, we find that such interactions are
different from those of the nonlinear Schrodinger equation and Hirota equation.
When those solitons interact with each other, the singular-I soliton is shape
preserving, while the singular-II and nonsingular solitons may be shape
preserving or shape changing. Such elastic and inelastic interaction phenomena in
a scalar equation might enrich the knowledge of soliton behavior, which could be
expected to be experimentally observed.
PMID- 28415233
TI - Two mechanisms forming a comblike step pattern induced by a moving linear adatom
source.
AB - We carry out phase field simulations to study properties of the comblike step
patterns induced by an adatom source. When an adatom source advances right in
front of a step, step wandering is caused by the asymmetry of the surface
diffusion field and small protrusions are formed. If the velocity of the source
V_{p} is smaller than a critical value V_{p}^{c}, the protrusions follow the
adatom source with coarsening of the step pattern, and a regular comblike pattern
with finger-like protrusions is formed. With a sufficiently small V_{p}, the gap
of the supersaturation is large at the adatom source. Since the period of
protrusions, Lambda, decreases with increasing V_{p}, the coarsening of step
pattern is irrelevant for the protrusions to catch up with the adatom source.
Near V_{p}^{c}, the gap of the supersaturation at the adatom source is small.
Taking account of the increase in Lambda with increasing V_{p}, the coarsening of
the step pattern is essential for the protrusions to follow the adatom source.
PMID- 28415234
TI - Global relativistic effects in chaotic scattering.
AB - The phenomenon of chaotic scattering is very relevant in different fields of
science and engineering. It has been mainly studied in the context of Newtonian
mechanics, where the velocities of the particles are low in comparison with the
speed of light. Here, we analyze global properties such as the escape time
distribution and the decay law of the Henon-Heiles system in the context of
special relativity. Our results show that the average escape time decreases with
increasing values of the relativistic factor beta. As a matter of fact, we have
found a crossover point for which the KAM islands in the phase space are
destroyed when beta?0.4. On the other hand, the study of the survival probability
of particles in the scattering region shows an algebraic decay for values of
beta<=0.4, and this law becomes exponential for beta>0.4. Surprisingly, a scaling
law between the exponent of the decay law and the beta factor is uncovered where
a quadratic fitting between them is found. The results of our numerical
simulations agree faithfully with our qualitative arguments. We expect this work
to be useful for a better understanding of both chaotic and relativistic systems.
PMID- 28415235
TI - General velocity, pressure, and initial condition for two-dimensional and three
dimensional lattice Boltzmann simulations.
AB - In this paper, an alternative approach to implement initial and boundary
conditions in the lattice Boltzmann method is presented. The main idea is to
approximate the nonequilibrium component of distribution functions as a third
order power series in the lattice velocities and formulate a procedure to
determine boundary node distributions by using fluid variables, consistent with
such an expansion. The velocity shift associated with the body force effects is
included in this scheme, along with an approximation to determine the mass
density in complex geometries. Different strategies based on the present scheme
are developed to implement velocity and pressure conditions for arbitrarily
shaped boundaries, using the D2Q9, D3Q15, D3Q19 and D3Q27 lattices, in two and
three space dimensions, respectively. The proposed treatment is tested against
several well-established problems, showing second-order spatial accuracy and
often improved behavior as compared to various existing methods, with no
appreciable computational overhead.
PMID- 28415236
TI - Globally attracting synchrony in a network of oscillators with all-to-all
inhibitory pulse coupling.
AB - The synchronization tendencies of networks of oscillators have been studied
intensely. We assume a network of all-to-all pulse-coupled oscillators in which
the effect of a pulse is independent of the number of oscillators that
simultaneously emit a pulse and the normalized delay (the phase resetting) is a
monotonically increasing function of oscillator phase with the slope everywhere
less than 1 and a value greater than 2phi-1, where phi is the normalized phase.
Order switching cannot occur; the only possible solutions are globally attracting
synchrony and cluster solutions with a fixed firing order. For small conduction
delays, we prove the former stable and all other possible attractors nonexistent
due to the destabilizing discontinuity of the phase resetting at a phase of 0.
PMID- 28415237
TI - Latent geometry of bipartite networks.
AB - Despite the abundance of bipartite networked systems, their organizing principles
are less studied compared to unipartite networks. Bipartite networks are often
analyzed after projecting them onto one of the two sets of nodes. As a result of
the projection, nodes of the same set are linked together if they have at least
one neighbor in common in the bipartite network. Even though these projections
allow one to study bipartite networks using tools developed for unipartite
networks, one-mode projections lead to significant loss of information and
artificial inflation of the projected network with fully connected subgraphs.
Here we pursue a different approach for analyzing bipartite systems that is based
on the observation that such systems have a latent metric structure: network
nodes are points in a latent metric space, while connections are more likely to
form between nodes separated by shorter distances. This approach has been
developed for unipartite networks, and relatively little is known about its
applicability to bipartite systems. Here, we fully analyze a simple latent
geometric model of bipartite networks and show that this model explains the
peculiar structural properties of many real bipartite systems, including the
distributions of common neighbors and bipartite clustering. We also analyze the
geometric information loss in one-mode projections in this model and propose an
efficient method to infer the latent pairwise distances between nodes. Uncovering
the latent geometry underlying real bipartite networks can find applications in
diverse domains, ranging from constructing efficient recommender systems to
understanding cell metabolism.
PMID- 28415238
TI - Optimizing interconnections to maximize the spectral radius of interdependent
networks.
AB - The spectral radius (i.e., the largest eigenvalue) of the adjacency matrices of
complex networks is an important quantity that governs the behavior of many
dynamic processes on the networks, such as synchronization and epidemics. Studies
in the literature focused on bounding this quantity. In this paper, we
investigate how to maximize the spectral radius of interdependent networks by
optimally linking k internetwork connections (or interconnections for short). We
derive formulas for the estimation of the spectral radius of interdependent
networks and employ these results to develop a suite of algorithms that are
applicable to different parameter regimes. In particular, a simple algorithm is
to link the k nodes with the largest k eigenvector centralities in one network to
the node in the other network with a certain property related to both networks.
We demonstrate the applicability of our algorithms via extensive simulations. We
discuss the physical implications of the results, including how the optimal
interconnections can more effectively decrease the threshold of epidemic
spreading in the susceptible-infected-susceptible model and the threshold of
synchronization of coupled Kuramoto oscillators.
PMID- 28415239
TI - Motility of Escherichia coli in a quasi-two-dimensional porous medium.
AB - Bacterial migration through confined spaces is critical for several phenomena,
such as biofilm formation, bacterial transport in soils, and bacterial therapy
against cancer. In the present work, E. coli (strain K12-MG1655 WT) motility was
characterized by recording and analyzing individual bacterium trajectories in a
simulated quasi-two-dimensional porous medium. The porous medium was simulated by
enclosing, between slide and cover slip, a bacterial-culture sample mixed with
uniform 2.98-MUm-diameter spherical latex particles. The porosity of the medium
was controlled by changing the latex particle concentration. By statistically
analyzing several trajectory parameters (instantaneous velocity, turn angle, mean
squared displacement, etc.), and contrasting with the results of a random-walk
model developed ad hoc, we were able to quantify the effects that different
obstacle concentrations have upon bacterial motility.
PMID- 28415240
TI - Density-functional theory for fluid-solid and solid-solid phase transitions.
AB - We develop a theory to describe solid-solid phase transitions. The density
functional formalism of classical statistical mechanics is used to find an exact
expression for the difference in the grand thermodynamic potentials of the two
coexisting phases. The expression involves both the symmetry conserving and the
symmetry broken parts of the direct pair correlation function. The theory is used
to calculate phase diagram of systems of soft spheres interacting via inverse
power potentials u(r)=epsilon(sigma/r)^{n}, where parameter n measures softness
of the potential. We find that for 1/n<0.154 systems freeze into the face
centered cubic (fcc) structure while for 1/n>=0.154 the body-centred-cubic (bcc)
structure is preferred. The bcc structure transforms into the fcc structure upon
increasing the density. The calculated phase diagram is in good agreement with
the one found from molecular simulations.
PMID- 28415241
TI - Emergence of chimeras through induced multistability.
AB - Chimeras, namely coexisting desynchronous and synchronized dynamics, are formed
in an ensemble of identically coupled identical chaotic oscillators when the
coupling induces multiple stable attractors, and further when the basins of the
different attractors are intertwined in a complex manner. When there is coupling
induced multistability, an ensemble of identical chaotic oscillators-with global
coupling, or also under the influence of common noise or an external drive
(chaotic, periodic, or quasiperiodic)-inevitably exhibits chimeric behavior.
Induced multistability in the system leads to the formation of distinct
subpopulations, one or more of which support synchronized dynamics, while in
others the motion is asynchronous or incoherent. We study the mechanism for the
emergence of such chimeric states, and we discuss the generality of our results.
PMID- 28415242
TI - Renormalization-group theory for cooling first-order phase transitions in Potts
models.
AB - We develop a dynamic field-theoretic renormalization-group (RG) theory for
cooling first-order phase transitions in the Potts model. It is suggested that
the well-known imaginary fixed points of the q-state Potts model for q>10/3 in
the RG theory are the origin of the dynamic scaling found recently from numerical
simulations, apart from logarithmic corrections. This indicates that the real and
imaginary fixed points of the Potts model are both physical and control the
scalings of the continuous and discontinuous phase transitions, respectively, of
the model. Our one-loop results for the scaling exponents are already not far
away from the numerical results. Further, the scaling exponents depend on q only
slightly, consistent with the numerical results. Therefore, the theory is
believed to provide a natural explanation of the dynamic scaling including the
scaling exponents and their scaling laws for various observables in the cooling
first-order phase transition of the Potts model.
PMID- 28415243
TI - Numerical linked cluster expansions for quantum quenches in one-dimensional
lattices.
AB - We discuss the application of numerical linked cluster expansions (NLCEs) to
study one dimensional lattice systems in thermal equilibrium and after quantum
quenches from thermal equilibrium states. For the former, we calculate
observables in the grand canonical ensemble, and for the latter we calculate
observables in the diagonal ensemble. When converged, NLCEs provide results in
the thermodynamic limit. We use two different NLCEs: a maximally connected
expansion introduced in previous works and a site-based expansion. We compare the
effectiveness of both NLCEs. The site-based NLCE is found to work best for
systems in thermal equilibrium. However, in thermal equilibrium and after quantum
quenches, the site-based NLCE can diverge when the maximally connected one
converges. We relate this divergence to the exponentially large number of
clusters in the site-based NLCE and the behavior of the weights of observables in
those clusters. We discuss the effectiveness of resummations to cure the
divergence. Our NLCE calculations are compared to exact diagonalization ones in
lattices with periodic boundary conditions. NLCEs are found to outperform exact
diagonalization in periodic systems for all quantities studied.
PMID- 28415244
TI - Effect of the salt-induced micellar microstructure on the nonlinear shear flow
behavior of ionic cetylpyridinium chloride surfactant solutions.
AB - The shear flow dynamics of linear and branched wormlike micellar systems based on
cetylpyridinium chloride and sodium salicylate in brine solution is investigated
through rheometric and scattering techniques. In particular, the flow and the
structural flow response are explored via velocimetry measurements and
rheological and rheometric small-angle neutron scattering (SANS) experiments,
respectively. Although all micellar solutions display a similar shear thinning
behavior in the nonlinear regime, the experimental results show that shear
banding sets in only when the micelle contour length L[over -] is sufficiently
long, independent of the nature of the micellar connections (either linear or
branched micelles). Using rheometric SANS, we observe that the shear banding
systems both show very similar orientational ordering as a function of
Weissenberg number, while the short branched micelles manifest an unexpected
increase of ordering at very low Weissenberg numbers. This suggests the presence
of an additional flow-induced relaxation process that is peculiar for branched
systems.
PMID- 28415245
TI - Converting heat into directed transport on a tilted lattice.
AB - We present a self-contained engine, which is made of one or more two-level
systems, each of which is coupled to a single bath, as well as to a common load
composed of a particle on a tilted lattice. We show that an increase in time of
energy and entropy in the system composed of the spins and the particle, due to
the interaction with the bath, can set the particle into upward motion at an
average constant speed, even when driven by a single spin connected to a single
bath. When considering an ensemble of different spins, the velocity of the
particle is larger when the tilt is on resonance with any of the spins' energy
splitting. Interestingly, we find regimes where the spins' polarization enters
periodic cycles with the oscillation period being determined by the tilt of the
lattice.
PMID- 28415246
TI - Synchronization dynamics on the picosecond time scale in coupled Josephson
junction neurons.
AB - Conventional digital computation is rapidly approaching physical limits for speed
and energy dissipation. Here we fabricate and test a simple neuromorphic circuit
that models neuronal somas, axons, and synapses with superconducting Josephson
junctions. The circuit models two mutually coupled excitatory neurons. In some
regions of parameter space the neurons are desynchronized. In others, the
Josephson neurons synchronize in one of two states, in-phase or antiphase. An
experimental alteration of the delay and strength of the connecting synapses can
toggle the system back and forth in a phase-flip bifurcation. Firing
synchronization states are calculated >70 000 times faster than conventional
digital approaches. With their speed and low energy dissipation (10^{
17}J/spike), this set of proof-of-concept experiments establishes Josephson
junction neurons as a viable approach for improvements in neuronal computation as
well as applications in neuromorphic computing.
PMID- 28415247
TI - Renormalization group analysis for an asymmetric simple exclusion process.
AB - A perturbative renormalization group method is used to obtain steady-state
density profiles of a totally asymmetric simple exclusion process with particle
adsorption and evaporation. This method allows us to obtain a globally valid
solution for the density profile without the asymptotic matching of bulk and
boundary layer solutions. In addition, we show a nontrivial scaling of the
boundary layer width with the system size close to specific phase boundaries.
PMID- 28415248
TI - Breakdown of nonlinear elasticity in stress-controlled thermal amorphous solids.
AB - In recent work it was clarified that amorphous solids under strain control do not
possess nonlinear elastic theory in the sense that the shear modulus exists but
nonlinear moduli exhibit sample-to-sample fluctuations that grow without bound
with the system size. More relevant, however, for experiments are the conditions
of stress control. In the present Rapid Communication we show that also under
stress control the shear modulus exists, but higher-order moduli show unbounded
sample-to-sample fluctuation. The unavoidable consequence is that the
characterization of stress-strain curves in experiments should be done with a
stress-dependent shear modulus rather than with nonlinear expansions.
PMID- 28415249
TI - Traveling waves and breathers in an excitatory-inhibitory neural field.
AB - We study existence and stability of traveling activity bump solutions in an
excitatory-inhibitory (E-I) neural field with Heaviside firing rate functions by
deriving existence conditions for traveling bumps and an Evans function to
analyze their spectral stability. Subsequently, we show that these existence and
stability results reduce, in the limit of wave speed c->0, to the equivalent
conditions developed for the stationary bump case. Using the results for the
stationary bump case, we show that drift bifurcations of stationary bumps serve
as a mechanism for generating traveling bump solutions in the E-I neural field as
parameters are varied. Furthermore, we explore the interrelations between
stationary and traveling types of bumps and breathers (time-periodic oscillatory
bumps) by bridging together analytical and simulation results for stationary and
traveling bumps and their bifurcations in a region of parameter space.
Interestingly, we find evidence for a codimension-2 drift-Hopf bifurcation
occurring as two parameters, inhibitory time constant tau and I-to-I synaptic
connection strength w[over -]_{ii}, are varied and show that the codimension-2
point serves as an organizing center for the dynamics of these four types of
spatially localized solutions. Additionally, we describe a case involving
subcritical bifurcations that lead to traveling waves and breathers as tau is
varied.
PMID- 28415250
TI - Compressible cell gas models for asymmetric fluid criticality.
AB - We thoroughly describe a class of models recently presented by Fisher and
coworkers [Phys. Rev. Lett. 116, 040601 (2016)]PRLTAO0031
900710.1103/PhysRevLett.116.040601. The crucial feature of such models, termed
compressible cell gases (CCGs), is that the individual cell volumes of a lattice
gas are allowed to fluctuate. They are studied via the seldom-used (MU, p, T)
ensemble, which leads to their exact mapping onto the Ising model. Remarkably,
CCGs obey complete scaling, a formulation for the thermodynamic behavior of
fluids near the gas-liquid critical point that accommodates features inherent to
the asymmetric nature of this phase transition like the Yang-Yang (YY) and
singular coexistence-curve diameter anomalies. The CCG_{0} models generated when
volumes vary freely reveal local free volume fluctuations as the origin of these
phenomena. Local energy-volume coupling is found to be another relevant
microscopic factor. Furthermore, the CCG class is greatly extended by using the
decoration transformation, with an interesting example being the Sastry
Debenedetti-Sciortino-Stanley model for hydrogen bonding in low-temperature
water. The magnitude of anomalies is characterized by a single parameter, the YY
ratio, which for the models so far considered here ranges from -infinity to 1/2.
PMID- 28415251
TI - Velocity distribution of a driven inelastic one-component Maxwell gas.
AB - The nature of the velocity distribution of a driven granular gas, though well
studied, is unknown as to whether it is universal or not, and, if universal, what
it is. We determine the tails of the steady state velocity distribution of a
driven inelastic Maxwell gas, which is a simple model of a granular gas where the
rate of collision between particles is independent of the separation as well as
the relative velocity. We show that the steady state velocity distribution is
nonuniversal and depends strongly on the nature of driving. The asymptotic
behavior of the velocity distribution is shown to be identical to that of a
noninteracting model where the collisions between particles are ignored. For
diffusive driving, where collisions with the wall are modeled by an additive
noise, the tails of the velocity distribution is universal only if the noise
distribution decays faster than exponential.
PMID- 28415252
TI - Clogging and jamming transitions in periodic obstacle arrays.
AB - We numerically examine clogging transitions for bidisperse disks flowing through
a two-dimensional periodic obstacle array. We show that clogging is a
probabilistic event that occurs through a transition from a homogeneous flowing
state to a heterogeneous or phase-separated jammed state where the disks form
dense connected clusters. The probability for clogging to occur during a fixed
time increases with increasing particle packing and obstacle number. For driving
at different angles with respect to the symmetry direction of the obstacle array,
we show that certain directions have a higher clogging susceptibility. It is also
possible to have a size-specific clogging transition in which one disk size
becomes completely immobile while the other disk size continues to flow.
PMID- 28415253
TI - Nonequilibrium random matrix theory: Transition probabilities.
AB - In this paper we present an analytic method for calculating the transition
probability between two random Gaussian matrices with given eigenvalue spectra in
the context of Dyson Brownian motion. We show that in the Coulomb gas language,
in large N limit, memory of the initial state is preserved in the form of a
universal linear potential acting on the eigenvalues. We compute the likelihood
of any given transition as a function of time, showing that as memory of the
initial state is lost, transition probabilities converge to those of the static
ensemble.
PMID- 28415254
TI - Anomalous diffusion in viscoelastic media with active force dipoles.
AB - With the use of the "two-fluid model," we discuss anomalous diffusion induced by
active force dipoles in viscoelastic media. Active force dipoles, such as
proteins and bacteria, generate nonthermal fluctuating flows that lead to a
substantial increment of the diffusion. Using the partial Green's function of the
two-fluid model, we first obtain passive (thermal) two-point correlation
functions such as the displacement cross-correlation function between the two
point particles separated by a finite distance. We then calculate active
(nonthermal) one-point and two-point correlation functions due to active force
dipoles. The time correlation of a force dipole is assumed to decay exponentially
with a characteristic time scale. We show that the active component of the
displacement cross-correlation function exhibits various crossovers from super
diffusive to subdiffusive behaviors depending on the characteristic time scales
and the particle separation. Our theoretical results are intimately related to
the microrheology technique to detect fluctuations in nonequilibrium environment.
PMID- 28415255
TI - Numerical study of one-dimensional compression of granular materials. I. Stress
strain behavior, microstructure, and irreversibility.
AB - The behavior of a model granular material, made of slightly polydisperse beads
with Hertz-Mindlin elastic-frictional contacts, in oedometric compression (i.e.,
compression along one axis, with no lateral strain) is studied by grain-level
numerical simulations. We systematically investigate the influence of the
(idealized) packing process on the microstructure and stresses in the initial,
weakly confined equilibrium state, and prepare both isotropic and anisotropic
configurations differing in solid fraction Phi and coordination number z. Phi
(ranging from maximally dense to moderately loose), z (which might vary
independently of Phi in dense systems), fabric and force anisotropy parameters,
and the ratio K_{0} of lateral stresses sigma_{2}=sigma_{3} to stress sigma_{1}
in the compression direction are monitored in oedometric compression in which
sigma_{1} varies by more than three orders of magnitude. K_{0} reflects the
anisotropy of the assembling process and may remain nearly constant in further
loading if the material is already oedometrically compressed (as a granular gas)
in the preparation stage. Otherwise, it tends to decrease steadily over the
investigated stress range. It is related to force and fabric anisotropy
parameters by a simple formula. Elastic moduli, separately computed with an
appropriate matrix method, may express the response to very small stress
increments about the transversely isotropic well-equilibrated states along the
loading path, although oedometric compression proves an essentially anelastic
process, mainly due to friction mobilization, with large irreversible effects
apparent upon unloading. While the evolution of axial strain epsilon_{1} and
solid fraction Phi (or of the void ratio e=-1+1/Phi) with axial stress sigma_{1}
is very nearly reversible, especially in dense samples, z is observed to decrease
(as previously observed in isotropic compression) after a compression cycle if
its initial value was high. K_{0} relates to the evolution of internal variables
and may exceed 1 in unloading. The considerably greater irreversibility of
oedometric compression reported in sands, compared to our model systems, should
signal contact plasticity or damage.
PMID- 28415256
TI - Turbulent compressible fluid: Renormalization group analysis, scaling regimes,
and anomalous scaling of advected scalar fields.
AB - We study a model of fully developed turbulence of a compressible fluid, based on
the stochastic Navier-Stokes equation, by means of the field-theoretic
renormalization group. In this approach, scaling properties are related to the
fixed points of the renormalization group equations. Previous analysis of this
model near the real-world space dimension 3 identified a scaling regime [N. V.
Antonov et al., Theor. Math. Phys. 110, 305 (1997)TMPHAH0040
577910.1007/BF02630456]. The aim of the present paper is to explore the existence
of additional regimes, which could not be found using the direct perturbative
approach of the previous work, and to analyze the crossover between different
regimes. It seems possible to determine them near the special value of space
dimension 4 in the framework of double y and E expansion, where y is the exponent
associated with the random force and E=4-d is the deviation from the space
dimension 4. Our calculations show that there exists an additional fixed point
that governs scaling behavior. Turbulent advection of a passive scalar (density)
field by this velocity ensemble is considered as well. We demonstrate that
various correlation functions of the scalar field exhibit anomalous scaling
behavior in the inertial-convective range. The corresponding anomalous exponents,
identified as scaling dimensions of certain composite fields, can be
systematically calculated as a series in y and E. All calculations are performed
in the leading one-loop approximation.
PMID- 28415257
TI - Effect of single-particle magnetostriction on the shear modulus of compliant
magnetoactive elastomers.
AB - The influence of an external magnetic field on the static shear strain and the
effective shear modulus of a magnetoactive elastomer (MAE) is studied
theoretically in the framework of a recently introduced approach to the single
particle magnetostriction mechanism [V. M. Kalita et al., Phys. Rev. E 93, 062503
(2016)10.1103/PhysRevE.93.062503]. The planar problem of magnetostriction in an
MAE with magnetically soft inclusions in the form of a thin disk (platelet)
having the magnetic anisotropy in the plane of this disk is solved analytically.
An external magnetic field acts with torques on magnetic filler particles,
creates mechanical stresses in the vicinity of inclusions, induces shear strain,
and increases the effective shear modulus of these composite materials. It is
shown that the largest effect of the magnetic field on the effective shear
modulus should be expected in MAEs with soft elastomer matrices, where the shear
modulus of the matrix is less than the magnetic anisotropy constant of
inclusions. It is derived that the effective shear modulus is nonlinearly
dependent on the external magnetic field and approaches the saturation value in
magnetic fields exceeding the field of particle anisotropy. It is shown that
model calculations of the effective shear modulus correspond to a
phenomenological definition of effective elastic moduli and magnetoelastic
coupling constants. The obtained theoretical results compare well with known
experimental data. Determination of effective elastic coefficients in MAEs and
their dependence on magnetic field is discussed. The concentration dependence of
the effective shear modulus at higher filler concentrations has been estimated
using the method of Pade approximants, which predicts that both the absolute and
relative changes of the magnetic-field-dependent effective shear modulus will
significantly increase with the growing concentration of filler particles.
PMID- 28415258
TI - Fluctuations around mean walking behaviors in diluted pedestrian flows.
AB - Understanding and modeling the dynamics of pedestrian crowds can help with
designing and increasing the safety of civil facilities. A key feature of a crowd
is its intrinsic stochasticity, appearing even under very diluted conditions, due
to the variability in individual behaviors. Individual stochasticity becomes even
more important under densely crowded conditions, since it can be nonlinearly
magnified and may lead to potentially dangerous collective behaviors. To
understand quantitatively crowd stochasticity, we study the real-life dynamics of
a large ensemble of pedestrians walking undisturbed, and we perform a statistical
analysis of the fully resolved pedestrian trajectories obtained by a yearlong
high-resolution measurement campaign. Our measurements have been carried out in a
corridor of the Eindhoven University of Technology via a combination of Microsoft
Kinect 3D range sensor and automatic head-tracking algorithms. The temporal
homogeneity of our large database of trajectories allows us to robustly define
and separate average walking behaviors from fluctuations parallel and orthogonal
with respect to the average walking path. Fluctuations include rare events when
individuals suddenly change their minds and invert their walking directions. Such
tendency to invert direction has been poorly studied so far, even if it may have
important implications on the functioning and safety of facilities. We propose a
model for the dynamics of undisturbed pedestrians, based on stochastic
differential equations, that provides a good agreement with our field
observations, including the occurrence of rare events.
PMID- 28415259
TI - Effects of disorder and chain stiffening on the elasticity of flexible polymer
networks.
AB - We examine how the distribution of contour lengths and the high-stretch
stiffening of individual chain segments affect the macroscopic shear modulus of
flexible polymer gels, using a two-dimensional numerical model in which polymer
segments form a triangular network and disorder is introduced by varying their
contour lengths. We show that, in the relevant parameter range: (i) the nonaffine
contribution to the shear modulus is negligible, i.e., the Born approximation is
satisfactory, and (ii) the shear modulus is dominated by the contribution
originating from equilibrium chain tensions. Moreover, mechanical equilibration
at the nodes induces specific correlations between the end-to-end distances and
contour lengths of chain segments, which must be properly accounted for to
construct reasonable estimates of chain pressure and shear modulus.
PMID- 28415260
TI - Enhanced processing in arrays of optimally tuned nonlinear biomimetic sensors: A
coupling-mediated Ringelmann effect and its dynamical mitigation.
AB - Inspired by recent results on self-tunability in the outer hair cells of the
mammalian cochlea, we describe an array of magnetic sensors where each individual
sensor can self-tune to an optimal operating regime. The self-tuning gives the
array its "biomimetic" features. We show that the overall performance of the
array can, as expected, be improved by increasing the number of sensors but,
however, coupling between sensors reduces the overall performance even though the
individual sensors in the system could see an improvement. We quantify the
similarity of this phenomenon to the Ringelmann effect that was formulated 103
years ago to account for productivity losses in human and animal groups. We
propose a global feedback scheme that can be used to greatly mitigate the
performance degradation that would, normally, stem from the Ringelmann effect.
PMID- 28415261
TI - Robustness of spatial patterns in buffered reaction-diffusion systems and its
reciprocity with phase plasticity.
AB - The robustness of spatial patterns against perturbations is an indispensable
property of developmental processes for organisms, which need to adapt to
changing environments. Although specific mechanisms for this robustness have been
extensively investigated, little is known about a general mechanism for achieving
robustness in reaction-diffusion systems. Here, we propose a buffered reaction
diffusion system, in which active states of chemicals mediated by buffer
molecules contribute to reactions, and demonstrate that robustness of the pattern
wavelength is achieved by the dynamics of the buffer molecule. This robustness is
analytically explained as a result of the scaling properties of the buffered
system, which also lead to a reciprocal relationship between the wavelength's
robustness and the plasticity of the spatial phase upon external perturbations.
Finally, we explore the relevance of this reciprocity to biological systems.
PMID- 28415262
TI - Thermophoretic force on nanocylinders in the free molecule regime.
AB - We theoretically investigate the thermophoresis of nanocylinders in the free
molecule regime, wherein the nonrigid-body effect is taken into account. The
analytical formulas of the thermophoretic forces on cylinders suspended in both
simple gases and binary gas mixtures are derived for the two limiting collision
models, i.e., specular and diffuse scatterings, based on the gas kinetic theory.
In the limit of the rigid-body collision, the expressions can be reduced to the
theoretical results of Garcia-Ybarra and Rosner [AIChE J. 35, 139
(1989)10.1002/aic.690350115]. The thermophoretic velocities of the nanocylinders
(including carbon nanotubes and long-chain n-alkanes) have been evaluated and it
is found that the influence of the nonrigid-body effect on thermophoresis is
significant for the case of small cylinder radius and low temperatures.
PMID- 28415263
TI - Percolation on networks with weak and heterogeneous dependency.
AB - In real networks, the dependency between nodes is ubiquitous; however, the
dependency is not always complete and homogeneous. In this paper, we propose a
percolation model with weak and heterogeneous dependency; i.e., dependency
strengths could be different between different nodes. We find that the
heterogeneous dependency strength will make the system more robust, and for
various distributions of dependency strengths both continuous and discontinuous
percolation transitions can be found. For Erdos-Renyi networks, we prove that the
crossing point of the continuous and discontinuous percolation transitions is
dependent on the first five moments of the dependency strength distribution. This
indicates that the discontinuous percolation transition on networks with
dependency is determined not only by the dependency strength but also by its
distribution. Furthermore, in the area of the continuous percolation transition,
we also find that the critical point depends on the first and second moments of
the dependency strength distribution. To validate the theoretical analysis, cases
with two different dependency strengths and Gaussian distribution of dependency
strengths are presented as examples.
PMID- 28415264
TI - Self-energy matrices for electron transport calculations within the real-space
finite-difference formalism.
AB - The self-energy term used in transport calculations, which describes the coupling
between electrode and transition regions, is able to be evaluated only from a
limited number of the propagating and evanescent waves of a bulk electrode. This
obviously contributes toward the reduction of the computational expenses in
transport calculations. In this paper, we present a mathematical formula for
reducing the computational expenses further without using any approximation and
without losing accuracy. So far, the self-energy term has been handled as a
matrix with the same dimension as the Hamiltonian submatrix representing the
interaction between an electrode and a transition region. In this work, through
the singular-value decomposition of the submatrix, the self-energy matrix is
handled as a smaller matrix, whose dimension is the rank number of the
Hamiltonian submatrix. This procedure is practical in the case of using the
pseudopotentials in a separable form, and the computational expenses for
determining the self-energy matrix are reduced by 90% when employing a code based
on the real-space finite-difference formalism and projector-augmented wave
method. In addition, this technique is applicable to the transport calculations
using atomic or localized basis sets. Adopting the self-energy matrices obtained
from this procedure, we present the calculation of the electron transport
properties of C_{20} molecular junctions. The application demonstrates that the
electron transmissions are sensitive to the orientation of the molecule with
respect to the electrode surface. In addition, channel decomposition of the
scattering wave functions reveals that some unoccupied C_{20} molecular orbitals
mainly contribute to the electron conduction through the molecular junction.
PMID- 28415265
TI - Comparative statistics of selected subgrid-scale models in large-eddy simulations
of decaying, supersonic magnetohydrodynamic turbulence.
AB - Large-eddy simulations (LES) are a powerful tool in understanding processes that
are inaccessible by direct simulations due to their complexity, for example, in
the highly turbulent regime. However, their accuracy and success depends on a
proper subgrid-scale (SGS) model that accounts for the unresolved scales in the
simulation. We evaluate the applicability of two traditional SGS models, namely
the eddy-viscosity (EV) and the scale-similarity (SS) models, and one recently
proposed nonlinear (NL) SGS model in the realm of compressible
magnetohydrodynamic (MHD) turbulence. Using 209 simulations of decaying,
supersonic (initial sonic Mach number M_{s}~3) MHD turbulence with a shock
capturing scheme and varying resolution, SGS model, and filter, we analyze the
ensemble statistics of kinetic and magnetic energy spectra and structure
functions. Furthermore, we compare the temporal evolution of lower- and higher
order statistical moments of the spatial distributions of kinetic and magnetic
energy, vorticity, current density, and dilatation magnitudes. We find no
statistical influence on the evolution of the flow by any model if grid-scale
quantities are used to calculate SGS contributions. In addition, the SS models,
which employ an explicit filter, have no impact in general. On the contrary, both
the EV and NL models change the statistics if an explicit filter is used. For
example, they slightly increase the dissipation on the smallest scales. We
demonstrate that the nonlinear model improves higher-order statistics already
with a small explicit filter, i.e., a three-point stencil. The results of, e.g.,
the structure functions or the skewness and kurtosis of the current density
distribution are closer to the ones obtained from simulations at higher
resolution. In addition, no additional regularization to stabilize the model is
required. We conclude that the nonlinear model with a small explicit filter is
suitable for application in more complex scenarios when higher-order statistics
are important.
PMID- 28415266
TI - Cavitation and spallation in liquid metal droplets produced by subpicosecond
pulsed laser radiation.
AB - The deformation and fragmentation of liquid metal microdroplets by intense
subpicosecond Ti:sapphire laser pulses is experimentally studied with
stroboscopic shadow photography. The experiments are performed at a peak
intensity of 10^{14}W/cm^{2} at the target's surface, which produces shock waves
with pressures in the Mbar range. As a result of such a strong impact, the
droplet is transformed into a complex-shaped hollow structure that undergoes
asymmetrical expansion and eventually fragments. The hollow structure of the
expanding target is explained by the effects of cavitation and spallation that
follow the propagation of the laser-induced shock wave.
PMID- 28415267
TI - Dispersion relation for electromagnetic propagation in stochastic dielectric and
magnetic helical photonic crystals.
AB - We theoretically study the dispersion relation for axially propagating
electromagnetic waves throughout a one-dimensional helical structure whose pitch
and dielectric and magnetic properties are spatial random functions with specific
statistical characteristics. In the system of coordinates rotating with the
helix, by using a matrix formalism, we write the set of differential equations
that governs the expected value of the electromagnetic field amplitudes and we
obtain the corresponding dispersion relation. We show that the dispersion
relation depends strongly on the noise intensity introduced in the system and the
autocorrelation length. When the autocorrelation length increases at fixed
fluctuation and when the fluctuation augments at fixed autocorrelation length,
the band gap widens and the attenuation coefficient of electromagnetic waves
propagating in the random medium gets larger. By virtue of the degeneracy in the
imaginary part of the eigenvalues associated with the propagating modes, the
random medium acts as a filter for circularly polarized electromagnetic waves, in
which only the propagating backward circularly polarized wave can propagate with
no attenuation. Our results are valid for any kind of dielectric and magnetic
structures which possess a helical-like symmetry such as cholesteric and chiral
smectic-C liquid crystals, structurally chiral materials, and stressed
cholesteric elastomers.
PMID- 28415268
TI - Delayed collapses of Bose-Einstein condensates in relation to anti-de Sitter
gravity.
AB - We numerically investigate spherically symmetric collapses in the Gross
Pitaevskii equation with attractive nonlinearity in a harmonic potential. Even
below threshold for direct collapse, the wave function bounces off from the
origin and may eventually become singular after a number of oscillations in the
trapping potential. This is reminiscent of the evolution of Einstein gravity
sourced by a scalar field in anti de Sitter space where collapse corresponds to
black-hole formation. We carefully examine the long time evolution of the wave
function for continuous families of initial states in order to sharpen out this
qualitative coincidence which may bring new insights in both directions. On the
one hand, we comment on possible implications for the so-called Bosenova
collapses in cold atom Bose-Einstein condensates. On the other hand, Gross
Pitaevskii provides a toy model to study the relevance of either the resonance
conditions or the nonlinearity for the problem of anti de Sitter instability.
PMID- 28415269
TI - Relevant parameters in models of cell division control.
AB - A recent burst of dynamic single-cell data makes it possible to characterize the
stochastic dynamics of cell division control in bacteria. Different models were
used to propose specific mechanisms, but the links between them are poorly
explored. The lack of comparative studies makes it difficult to appreciate how
well any particular mechanism is supported by the data. Here, we describe a
simple and generic framework in which two common formalisms can be used
interchangeably: (i) a continuous-time division process described by a hazard
function and (ii) a discrete-time equation describing cell size across
generations (where the unit of time is a cell cycle). In our framework, this
second process is a discrete-time Langevin equation with simple physical
analogues. By perturbative expansion around the mean initial size (or
interdivision time), we show how this framework describes a wide range of
division control mechanisms, including combinations of time and size control, as
well as the constant added size mechanism recently found to capture several
aspects of the cell division behavior of different bacteria. As we show by
analytical estimates and numerical simulations, the available data are described
precisely by the first-order approximation of this expansion, i.e., by a "linear
response" regime for the correction of size fluctuations. Hence, a single
dimensionless parameter defines the strength and action of the division control
against cell-to-cell variability (quantified by a single "noise" parameter).
However, the same strength of linear response may emerge from several mechanisms,
which are distinguished only by higher-order terms in the perturbative expansion.
Our analytical estimate of the sample size needed to distinguish between second
order effects shows that this value is close to but larger than the values of the
current datasets. These results provide a unified framework for future studies
and clarify the relevant parameters at play in the control of cell division.
PMID- 28415270
TI - Pinning of scroll waves to flat and highly branched unexcitable heterogeneities.
AB - System heterogeneities such as organelles, cells, and anatomical features
strongly affect nonlinear wave patterns in biological systems. These effects are
more readily studied in otherwise homogeneous chemical reactions that allow the
introduction of tailored structures. Following this approach, we investigate the
dynamics of three-dimensional excitation vortices pinned to inert sheets with
circular holes arranged on a hexagonal lattice. Experiments with the Belousov
Zhabotinsky reaction and numerical simulations of an excitable reaction-diffusion
model reveal vortex pinning that circumvents the rapid collapse of free vortex
rings. The pinned scroll waves are affected by the topological mismatch between
their looplike rotation backbone and the branched pinning structure. Depending on
the initial condition, a multitude of stable vortex states exist, all of which
obey topological constraints, suggesting spinlike states for the involved
obstacle holes.
PMID- 28415271
TI - Mean-cluster approach indicates cell sorting time scales are determined by
collective dynamics.
AB - Cell migration is essential to cell segregation, playing a central role in tissue
formation, wound healing, and tumor evolution. Considering random mixtures of two
cell types, it is still not clear which cell characteristics define clustering
time scales. The mass of diffusing clusters merging with one another is expected
to grow as t^{d/d+2} when the diffusion constant scales with the inverse of the
cluster mass. Cell segregation experiments deviate from that behavior.
Explanations for that could arise from specific microscopic mechanisms or from
collective effects, typical of active matter. Here we consider a power law
connecting diffusion constant and cluster mass to propose an analytic approach to
model cell segregation where we explicitly take into account finite-size
corrections. The results are compared with active matter model simulations and
experiments available in the literature. To investigate the role played by
different mechanisms we considered different hypotheses describing cell-cell
interaction: differential adhesion hypothesis and different velocities
hypothesis. We find that the simulations yield normal diffusion for long time
intervals. Analytic and simulation results show that (i) cluster evolution
clearly tends to a scaling regime, disrupted only at finite-size limits; (ii)
cluster diffusion is greatly enhanced by cell collective behavior, such that for
high enough tendency to follow the neighbors, cluster diffusion may become
independent of cluster size; (iii) the scaling exponent for cluster growth
depends only on the mass-diffusion relation, not on the detailed local
segregation mechanism. These results apply for active matter systems in general
and, in particular, the mechanisms found underlying the increase in cell sorting
speed certainly have deep implications in biological evolution as a selection
mechanism.
PMID- 28415272
TI - Effect of node attributes on the temporal dynamics of network structure.
AB - Many natural and social networks evolve in time and their structures are dynamic.
In most networks, nodes are heterogeneous, and their roles in the evolution of
structure differ. This paper focuses on the role of individual attributes on the
temporal dynamics of network structure. We focus on a basic model for growing
networks that incorporates node attributes (which we call "quality"), and we
focus on the problem of forecasting the structural properties of the network in
arbitrary times for an arbitrary initial network. That is, we address the
following question: If we are given a certain initial network with given
arbitrary structure and known node attributes, then how does the structure change
in time as new nodes with given distribution of attributes join the network? We
solve the model analytically and obtain the quality-degree joint distribution and
degree correlations. We characterize the role of individual attributes in the
position of individual nodes in the hierarchy of connections. We confirm the
theoretical findings with Monte Carlo simulations.
PMID- 28415273
TI - Theory of deflagration in disordered media.
AB - The conventional theory of burning works well in the case of uniform media where
all system parameters are spatially independent. We develop a theory of burning
in disordered media. In this case, rare regions (hot spots) where the burning
process is more effective than on average may control the heat propagation in an
explosive sample. We show that most predictions of the theory of burning are
quite different from the conventional case. In particular, we show that a system
of randomly distributed hot spots exhibits a dynamic phase transition, which is
similar to the percolation transition. Depending on parameters of the system the
phase transition can be either first or second order. These two regimes are
separated by a tricritical point. The above results may be applicable to dynamics
of any overheated disordered system with a first order phase transition.
PMID- 28415274
TI - Earliest effects of sudden occlusions on pressure profiles in selected locations
of the human systemic arterial system.
AB - We have developed a numerical simulation method for predicting the time
dependence (wave form) of pressure at any location in the systemic arterial
system in humans. The method uses the matlab-Simulink environment. The input data
include explicitly the geometry of the arterial tree, treated up to an arbitrary
bifurcation level, and the elastic properties of arteries as well as rheological
parameters of blood. Thus, the impact of anatomic details of an individual
subject can be studied. The method is applied here to reveal the earliest stages
of mechanical reaction of the pressure profiles to sudden local blockages
(thromboses or embolisms) of selected arteries. The results obtained with a
purely passive model provide reference data indispensable for studies of longer
term effects due to neural and humoral mechanisms. The reliability of the results
has been checked by comparison of two available sets of anatomic, elastic, and
rheological data involving (i) 55 and (ii) 138 arterial segments. The remaining
arteries have been replaced with the appropriate resistive elements. Both models
are efficient in predicting an overall shift of pressure, whereas the accuracy of
the 55-segment model in reproducing the detailed wave forms and stabilization
times turns out dependent on the location of the blockage and the observation
point.
PMID- 28415275
TI - Effects of surface roughness on shear viscosity.
AB - This paper investigates the effect of surface roughness on fluid viscosity using
molecular dynamics simulations. The three-dimensional model consists of liquid
argon flowing between two solid walls whose surface roughness was modeled using
fractal theory. In tandem with previously published experimental work, our
results show that, while the viscosity in smooth channels remains constant across
the channel width, in the presence of surface roughness it increases close to the
walls. The increase of the boundary viscosity is further accentuated by an
increase in the depth of surface roughness. We attribute this behavior to the
increased momentum transfer at the boundary, a result of the irregular
distribution of fluid particles near rough surfaces. Furthermore, although the
viscosity in smooth channels has previously been shown to be independent of the
strength of the solid-liquid interaction, here we show that in the presence of
surface roughness, the boundary viscosity increases with the solid's wettability.
The paper concludes with an analytical description of the viscosity as a function
of the distance from the channel walls, the walls' surface roughness, and the
solid's wetting properties. The relation can potentially be used to adjust the
fluid dynamics equations for a more accurate description of microfluidic systems.
PMID- 28415276
TI - Transition of multidiffusive states in a biased periodic potential.
AB - We study a frequency-dependent damping model of hyperdiffusion within the
generalized Langevin equation. The model allows for the colored noise defined by
its spectral density, assumed to be proportional to omega^{delta-1} at low
frequencies with 01 noncrossing continuum DP in a random potential, to the sum of the
Nth largest eigenvalues of the GUE. Here, using replica methods, we provide an
important test of this conjecture by calculating exactly the right tails of both
PDFs and showing that they coincide for arbitrary N.
PMID- 28415281
TI - Stochastic dynamics and the predictability of big hits in online videos.
AB - The competition for the attention of users is a central element of the Internet.
Crucial issues are the origin and predictability of big hits, the few items that
capture a big portion of the total attention. We address these issues analyzing
10^{6} time series of videos' views from YouTube. We find that the average gain
of views is linearly proportional to the number of views a video already has, in
agreement with usual rich-get-richer mechanisms and Gibrat's law, but this fails
to explain the prevalence of big hits. The reason is that the fluctuations around
the average views are themselves heavy tailed. Based on these empirical
observations, we propose a stochastic differential equation with Levy noise as a
model of the dynamics of videos. We show how this model is substantially better
in estimating the probability of an ordinary item becoming a big hit, which is
considerably underestimated in the traditional proportional-growth models.
PMID- 28415282
TI - Traction reveals mechanisms of wall effects for microswimmers near boundaries.
AB - The influence of a plane boundary on low-Reynolds-number swimmers has frequently
been studied using image systems for flow singularities. However, the boundary
effect can also be expressed using a boundary integral representation over the
traction on the boundary. We show that examining the traction pattern on the
boundary caused by a swimmer can yield physical insights into determining when
far-field multipole models are accurate. We investigate the swimming velocities
and the traction of a three-sphere swimmer initially placed parallel to an
infinite planar wall. In the far field, the instantaneous effect of the wall on
the swimmer is well approximated by that of a multipole expansion consisting of a
force dipole and a force quadrupole. On the other hand, the swimmer close to the
wall must be described by a system of singularities reflecting its internal
structure. We show that these limits and the transition between them can be
independently identified by examining the traction pattern on the wall, either
using a quantitative correlation coefficient or by visual inspection. Last, we
find that for nonconstant propulsion, correlations between swimming stroke
motions and internal positions are important and not captured by time-averaged
traction on the wall, indicating that care must be taken when applying multipole
expansions to study boundary effects in cases of nonconstant propulsion.
PMID- 28415283
TI - Quantifying disorder in colloidal films spin-coated onto patterned substrates.
AB - Polycrystals of thin colloidal deposits, with thickness controlled by spin
coating speed, exhibit axial symmetry with local 4-fold and 6-fold symmetric
structures, termed orientationally correlated polycrystals (OCPs). While spin
coating is a very facile technique for producing large-area colloidal deposits,
the axial symmetry prevents us from achieving true long-range order. To obtain
true long-range order, we break this axial symmetry by introducing a patterned
surface topography and thus eliminate the OCP character. We then examine symmetry
independent methods to quantify order in these disordered colloidal deposits. We
find that all the information in the bond-orientational order parameters is well
captured by persistent homology analysis methods that only use the centers of the
particles as input data. It is expected that these methods will prove useful in
characterizing other disordered structures.
PMID- 28415284
TI - Theory of linear sweep voltammetry with diffuse charge: Unsupported electrolytes,
thin films, and leaky membranes.
AB - Linear sweep and cyclic voltammetry techniques are important tools for
electrochemists and have a variety of applications in engineering. Voltammetry
has classically been treated with the Randles-Sevcik equation, which assumes an
electroneutral supported electrolyte. In this paper, we provide a comprehensive
mathematical theory of voltammetry in electrochemical cells with unsupported
electrolytes and for other situations where diffuse charge effects play a role,
and present analytical and simulated solutions of the time-dependent Poisson
Nernst-Planck equations with generalized Frumkin-Butler-Volmer boundary
conditions for a 1:1 electrolyte and a simple reaction. Using these solutions, we
construct theoretical and simulated current-voltage curves for liquid and solid
thin films, membranes with fixed background charge, and cells with blocking
electrodes. The full range of dimensionless parameters is considered, including
the dimensionless Debye screening length (scaled to the electrode separation),
Damkohler number (ratio of characteristic diffusion and reaction times), and
dimensionless sweep rate (scaled to the thermal voltage per diffusion time). The
analysis focuses on the coupling of Faradaic reactions and diffuse charge
dynamics, although capacitive charging of the electrical double layers is also
studied, for early time transients at reactive electrodes and for nonreactive
blocking electrodes. Our work highlights cases where diffuse charge effects are
important in the context of voltammetry, and illustrates which regimes can be
approximated using simple analytical expressions and which require more careful
consideration.
PMID- 28415285
TI - Ellipsoidal Brownian self-driven particles in a magnetic field.
AB - We study the two-dimensional Brownian dynamics of an ellipsoidal paramagnetic
microswimmer moving at a low Reynolds number and subject to a magnetic field. Its
corresponding mean-square displacement, showing the effect of a particles's
shape, activity, and magnetic field on the microswimmer's diffusion, is
analytically obtained. Comparison between analytical and computational results
shows good agreement. In addition, the effect of self-propulsion on the
transition time from anisotropic to isotropic diffusion of the ellipse is
investigated.
PMID- 28415286
TI - Dissociation between two subgroups of the suprachiasmatic nucleus affected by the
number of damped oscillated neurons.
AB - In mammals, the main clock located in the suprachiasmatic nucleus (SCN) of the
brain synchronizes the body rhythms to the environmental light-dark cycle. The
SCN is composed of about 2*10^{4} neurons which can be classified into three
oscillatory phenotypes: self-sustained oscillators, damped oscillators, and
arrhythmic neurons. Exposed to an artificial external light-dark cycle with a
period of 22h instead of 24h, two subgroups of the SCN can become desynchronized
(dissociated). The ventrolateral (VL) subgroup receives photic input and is
entrained to the external cycle and a dorsomedial (DM) subgroup oscillates with
its endogenous (i.e., free running) period and is synchronized to the external
light-dark cycle through coupling from the VL. In the present study, we examined
the effects of damped oscillatory neurons on the dissociation between VL and DM
under an external 22h cycle. We found that, with increasing numbers of damped
oscillatory neurons located in the VL, the dissociation between the VL and DM
emerges, but if these neurons are increasingly present in the DM the dissociation
disappears. Hence, the damped oscillatory neurons in different subregions of the
SCN play distinct roles in the dissociation between the two subregions of the
SCN. This shows that synchrony between SCN subregions is affected by the number
of damped oscillatory neurons and the location of these cells. We suggest that
more knowledge on the number and the location of these cells may explain why some
species do show a dissociation between the subregions and others do not, as the
distribution of oscillatory types of neurons offers a plausible and novel
candidate mechanism to explain heterogeneity.
PMID- 28415287
TI - Effect of interstitial fluid on the fraction of flow microstates that precede
clogging in granular hoppers.
AB - We report on the nature of flow events for the gravity-driven discharge of glass
beads through a hole that is small enough that the hopper is susceptible to
clogging. In particular, we measure the average and standard deviation of the
distribution of discharged masses as a function of both hole and grain sizes. We
do so in air, which is usual, but also with the system entirely submerged under
water. This damps the grain dynamics and could be expected to dramatically affect
the distribution of the flow events, which are described in prior work as
avalanche-like. Though the flow is slower and the events last longer, we find
that the average discharge mass is only slightly reduced for submerged grains.
Furthermore, we find that the shape of the distribution remains exponential,
implying that clogging is still a Poisson process even for immersed grains. Per
Thomas and Durian [Phys. Rev. Lett. 114, 178001 (2015)PRLTAO0031
900710.1103/PhysRevLett.114.178001], this allows for an interpretation of the
average discharge mass in terms of the fraction of flow microstates that precede,
i.e., that effectively cause, a stable clog to form. Since this fraction is
barely altered by water, we conclude that the crucial microscopic variables are
the grain positions; grain momenta play only a secondary role in destabilizing
weak incipient arches. These insights should aid ongoing efforts to understand
the susceptibility of granular hoppers to clogging.
PMID- 28415288
TI - Foraging patterns in online searches.
AB - Nowadays online searches are undeniably the most common form of information
gathering, as witnessed by billions of clicks generated each day on search
engines. In this work we describe online searches as foraging processes that take
place on the semi-infinite line. Using a variety of quantities like probability
distributions and complementary cumulative distribution functions of step length
and waiting time as well as mean square displacements and entropies, we analyze
three different click-through logs that contain the detailed information of
millions of queries submitted to search engines. Notable differences between the
different logs reveal an increased efficiency of the search engines. In the
language of foraging, the newer logs indicate that online searches overwhelmingly
yield local searches (i.e., on one page of links provided by the search engines),
whereas for the older logs the foraging processes are a combination of local
searches and relocation phases that are power law distributed. Our investigation
of click logs of search engines therefore highlights the presence of intermittent
search processes (where phases of local explorations are separated by power law
distributed relocation jumps) in online searches. It follows that good search
engines enable the users to find the information they are looking for through a
local exploration of a single page with search results, whereas for poor search
engine users are often forced to do a broader exploration of different pages.
PMID- 28415289
TI - Shear transformation distribution and activation in glasses at the atomic scale.
AB - We characterize shear transformations (STs) at the atomic scale in a model of
amorphous silicon using a mapping on Eshelby inclusions. We investigate the
effect of pressure, glass relaxation, as well as damage on the ST
characteristics. We show that the characteristic ST effective volume,
gamma_{0}V_{0}, product of the ST plastic shear strain gamma_{0} and volume
V_{0}, does not depend significantly on an applied pressure but increases with
accumulated plastic deformation from about 10A^{3} in the pseudoelastic regime to
about 60A^{3} once plastic flow sets in. Furthermore, by using nudged elastic
band calculations, we measure the energy barrier against ST activation. Analyzing
different paths leading to either an isolated ST or an avalanche, we show that
the barrier is systematically controlled by the first ST with an activation
volume equal to the effective volume of the ST at the activated state, which
represents only a fraction of the complete ST volume. The activation volume is
also found smaller for avalanches, presumably because of accumulated local
damage. This work provides essential information to build reliable mesoscale
models of plasticity.
PMID- 28415290
TI - Backward-stochastic-differential-equation approach to modeling of gene
expression.
AB - In this article, we introduce a backward method to model stochastic gene
expression and protein-level dynamics. The protein amount is regarded as a
diffusion process and is described by a backward stochastic differential equation
(BSDE). Unlike many other SDE techniques proposed in the literature, the BSDE
method is backward in time; that is, instead of initial conditions it requires
the specification of end-point ("final") conditions, in addition to the model
parametrization. To validate our approach we employ Gillespie's stochastic
simulation algorithm (SSA) to generate (forward) benchmark data, according to
predefined gene network models. Numerical simulations show that the BSDE method
is able to correctly infer the protein-level distributions that preceded a known
final condition, obtained originally from the forward SSA. This makes the BSDE
method a powerful systems biology tool for time-reversed simulations, allowing,
for example, the assessment of the biological conditions (e.g., protein
concentrations) that preceded an experimentally measured event of interest (e.g.,
mitosis, apoptosis, etc.).
PMID- 28415292
TI - Current redistribution in resistor networks: Fat-tail statistics in regular and
small-world networks.
AB - The redistribution of electrical currents in resistor networks after single-bond
failures is analyzed in terms of current-redistribution factors that are shown to
depend only on the topology of the network and on the values of the bond
resistances. We investigate the properties of these current-redistribution
factors for regular network topologies (e.g., d-dimensional hypercubic lattices)
as well as for small-world networks. In particular, we find that the statistics
of the current redistribution factors exhibits a fat-tail behavior, which
reflects the long-range nature of the current redistribution as determined by
Kirchhoff's circuit laws.
PMID- 28415291
TI - Experimental demonstration of low laser-plasma instabilities in gas-filled
spherical hohlraums at laser injection angle designed for ignition target.
AB - Octahedral spherical hohlraums with a single laser ring at an injection angle of
55^{?} are attractive concepts for laser indirect drive due to the potential for
achieving the x-ray drive symmetry required for high convergence implosions.
Laser-plasma instabilities, however, are a concern given the long laser
propagation path in such hohlraums. Significant stimulated Raman scattering has
been observed in cylindrical hohlraums with similar laser propagation paths
during the ignition campaign on the National Ignition Facility (NIF). In this
Rapid Communication, experiments demonstrating low levels of laser-driven plasma
instability (LPI) in spherical hohlraums with a laser injection angle of 55^{?}
are reported and compared to that observed with cylindrical hohlraums with
injection angles of 28.5^{?} and 55^{?}, similar to that of the NIF. Significant
LPI is observed with the laser injection of 28.5^{?} in the cylindrical hohlraum
where the propagation path is similar to the 55^{?} injection angle for the
spherical hohlraum. The experiments are performed on the SGIII laser facility
with a total 0.35-MUm incident energy of 93 kJ in a 3 nsec pulse. These
experiments demonstrate the role of hohlraum geometry in LPI and demonstrate the
need for systematic experiments for choosing the optimal configuration for
ignition studies with indirect drive inertial confinement fusion.
PMID- 28415293
TI - Two-component dark-bright solitons in three-dimensional atomic Bose-Einstein
condensates.
AB - In the present work, we revisit two-component Bose-Einstein condensates in their
fully three-dimensional (3D) form. Motivated by earlier studies of dark-bright
solitons in the 1D case, we explore the stability of these structures in their
fully 3D form in two variants. In one the dark soliton is planar and trapping a
planar bright (disk) soliton. In the other case, a dark spherical shell soliton
creates an effective potential in which a bright spherical shell of atoms is
trapped in the second component. We identify these solutions as numerically exact
states (up to a prescribed accuracy) and perform a Bogolyubov-de Gennes
linearization analysis that illustrates that both structures can be dynamically
stable in suitable intervals of sufficiently low chemical potentials. We
corroborate this finding theoretically by analyzing the stability via degenerate
perturbation theory near the linear limit of the system. When the solitary waves
are found to be unstable, we explore their dynamical evolution via direct
numerical simulations which, in turn, reveal wave forms that are more robust.
Finally, using the SO(2) symmetry of the model, we produce multi-dark-bright
planar or shell solitons involved in pairwise oscillatory motion.
PMID- 28415294
TI - Low thermal fluctuations in a system heated out of equilibrium.
AB - We study the mechanical fluctuations of a micrometer sized silicon cantilever
subjected to a strong heat flow, thus having a highly nonuniform local
temperature. In this nonequilibrium steady state, we show that fluctuations are
equivalent to the thermal noise of a cantilever at equilibrium around room
temperature, while its mean local temperature is several hundred degrees higher.
Changing the mechanical dissipation by adding a coating to the cantilever, we
recover the expected rise of fluctuations with the mean temperature. Our work
demonstrates that inhomogeneous dissipation mechanisms can decouple the amplitude
of thermal fluctuations from the average temperature. This property could be
useful to understand out-of-equilibrium fluctuating systems, or to engineer low
noise instruments.
PMID- 28415295
TI - Emergence of Levy walks in systems of interacting individuals.
AB - We propose a model of superdiffusive Levy walk as an emergent nonlinear
phenomenon in systems of interacting individuals. The aim is to provide a
qualitative explanation of recent experiments [G. Ariel et al., Nat. Commun. 6,
8396 (2015)2041-172310.1038/ncomms9396] revealing an intriguing behavior:
swarming bacteria fundamentally change their collective motion from simple
diffusion into a superdiffusive Levy walk dynamics. We introduce microscopic mean
field kinetic equations in which we combine two key ingredients: (1) alignment
interactions between individuals and (2) non-Markovian effects. Our interacting
run-and-tumble model leads to the superdiffusive growth of the mean-squared
displacement and the power-law distribution of run length with infinite variance.
The main result is that the superdiffusive behavior emerges as a cooperative
effect without using the standard assumption of the power-law distribution of run
distances from the inception. At the same time, we find that the collision and
repulsion interactions lead to the density-dependent exponential tempering of
power-law distributions. This qualitatively explains the experimentally observed
transition from superdiffusion to the diffusion of mussels as their density
increases [M. de Jager et al., Proc. R. Soc. B 281, 20132605 (2014)PRLBA40962
845210.1098/rspb.2013.2605].
PMID- 28415296
TI - Nuclear-magnetic-resonance relaxation due to the translational diffusion of fluid
confined to quasi-two-dimensional pores.
AB - Nuclear-magnetic-resonance (NMR) relaxation experimentation is an effective
technique for nondestructively probing the dynamics of proton-bearing fluids in
porous media. The frequency-dependent relaxation rate T_{1}^{-1} can yield a
wealth of information on the fluid dynamics within the pore provided data can be
fit to a suitable spin diffusion model. A spin diffusion model yields the dipolar
correlation function G(t) describing the relative translational motion of pairs
of ^{1}H spins which then can be Fourier transformed to yield T_{1}^{-1}. G(t)
for spins confined to a quasi-two-dimensional (Q2D) pore of thickness h is
determined using theoretical and Monte Carlo techniques. G(t) shows a transition
from three- to two-dimensional motion with the transition time proportional to
h^{2}. T_{1}^{-1} is found to be independent of frequency over the range 0.01-100
MHz provided h?5 nm and increases with decreasing frequency and decreasing h for
pores of thickness h<3 nm. T_{1}^{-1} increases linearly with the bulk water
diffusion correlation time tau_{b} allowing a simple and direct estimate of the
bulk water diffusion coefficient from the high-frequency limit of T_{1}^{-1}
dispersion measurements in systems where the influence of paramagnetic impurities
is negligible. Monte Carlo simulations of hydrated Q2D pores are executed for a
range of surface-to-bulk desorption rates for a thin pore. G(t) is found to
decorrelate when spins move from the surface to the bulk, display three
dimensional properties at intermediate times, and finally show a bulk-mediated
surface diffusion (Levy) mechanism at longer times. The results may be used to
interpret NMR relaxation rates in hydrated porous systems in which the
paramagnetic impurity density is negligible.
PMID- 28415297
TI - Toroidal-droplet instabilities in the presence of charge.
AB - Neutral toroidal droplets can break via the surface-tension-driven Rayleigh
Plateau instability. They can additionally exhibit a shrinking instability, which
is also driven by surface tension, whereby the handle progressively disappears.
We find that charging a toroidal droplet can qualitatively change the behavior
and cause the droplet to expand. We successfully model the transition from
shrinking to expanding, considering the pressure balance across the interface of
the torus. However, despite the change in behavior, charged toroidal droplets end
up breaking into spherical droplets. We quantify how the wavelength of the
fastest unstable mode associated to this breakup depends on the applied voltage
and compare the results with theoretical expectations for charged cylindrical
jets.
PMID- 28415298
TI - Maxwell iteration for the lattice Boltzmann method with diffusive scaling.
AB - In this work, we present an alternative derivation of the Navier-Stokes equations
from Bhatnagar-Gross-Krook models of the lattice Boltzmann method with diffusive
scaling. This derivation is based on the Maxwell iteration and can expose certain
important features of the lattice Boltzmann solutions. Moreover, it will be seen
to be much more straightforward and logically clearer than the existing
approaches including the Chapman-Enskog expansion.
PMID- 28415299
TI - Measurement-induced operation of two-ion quantum heat machines.
AB - We show how one can implement a quantum heat machine by using two interacting
trapped ions, in presence of a thermal bath. The electronic states of the ions
act like a working substance, while the vibrational mode is modelled as the cold
bath. The heat exchange with the cold bath is mimicked by the projective
measurement of the electronic states. We show how such measurement in a suitable
basis can lead to either a quantum heat engine or a refrigerator, which undergoes
a quantum Otto cycle. The local magnetic field is adiabatically changed during
the heat cycle. The performance of the heat machine depends upon the interaction
strength between the ions, the magnetic fields, and the measurement cost. In our
model, the coupling to the hot and the cold baths is never switched off in an
alternative fashion during the heat cycle, unlike other existing proposals of
quantum heat engines. This makes our proposal experimentally realizable using
current tapped-ion technology.
PMID- 28415300
TI - Influence of disorder on generation and probability of extreme events in Salerno
lattices.
AB - Extreme events (EEs) in nonlinear and/or disordered one-dimensional photonic
lattice systems described by the Salerno model with on-site disorder are studied.
The goal is to explain particular properties of these phenomena, essentially
related to localization of light in the presence of nonlinear and/or nonlocal
couplings in the considered systems. Combining statistical and nonlinear
dynamical methods and measures developed in the framework of the theory of
localization phenomena in disordered and nonlinear systems, particularities of
EEs are qualitatively clarified. Findings presented here indicate that the best
environment for EEs' creation are disordered near-integrable Salerno lattices. In
addition, it is been shown that the leading role in the generation and dynamical
properties of EEs in the considered model is played by modulation instability,
i.e., by nonlinearities in the system, although EEs can be induced in linear
lattices with on-site disorder too.
PMID- 28415301
TI - Nonlinear signaling on biological networks: The role of stochasticity and
spectral clustering.
AB - Signal transduction within biological cells is governed by networks of
interacting proteins. Communication between these proteins is mediated by
signaling molecules which bind to receptors and induce stochastic transitions
between different conformational states. Signaling is typically a cooperative
process which requires the occurrence of multiple binding events so that reaction
rates have a nonlinear dependence on the amount of signaling molecule. It is this
nonlinearity that endows biological signaling networks with robust switchlike
properties which are critical to their biological function. In this study we
investigate how the properties of these signaling systems depend on the network
architecture. Our main result is that these nonlinear networks exhibit
bistability where the network activity can switch between states that correspond
to a low and high activity level. We show that this bistable regime emerges at a
critical coupling strength that is determined by the spectral structure of the
network. In particular, the set of nodes that correspond to large components of
the leading eigenvector of the adjacency matrix determines the onset of
bistability. Above this transition the eigenvectors of the adjacency matrix
determine a hierarchy of clusters, defined by its spectral properties, which are
activated sequentially with increasing network activity. We argue further that
the onset of bistability occurs either continuously or discontinuously depending
upon whether the leading eigenvector is localized or delocalized. Finally, we
show that at low network coupling stochastic transitions to the active branch are
also driven by the set of nodes that contribute more strongly to the leading
eigenvector. However, at high coupling, transitions are insensitive to network
structure since the network can be activated by stochastic transitions of a few
nodes. Thus this work identifies important features of biological signaling
networks that may underlie their biological function.
PMID- 28415302
TI - Generalized three-dimensional lattice Boltzmann color-gradient method for
immiscible two-phase pore-scale imbibition and drainage in porous media.
AB - This article presents a three-dimensional numerical framework for the simulation
of fluid-fluid immiscible compounds in complex geometries, based on the multiple
relaxation-time lattice Boltzmann method to model the fluid dynamics and the
color-gradient approach to model multicomponent flow interaction. New lattice
weights for the lattices D3Q15, D3Q19, and D3Q27 that improve the Galilean
invariance of the color-gradient model as well as for modeling the interfacial
tension are derived and provided in the Appendix. The presented method proposes
in particular an approach to model the interaction between the fluid compound and
the solid, and to maintain a precise contact angle between the two-component
interface and the wall. Contrarily to previous approaches proposed in the
literature, this method yields accurate solutions even in complex geometries and
does not suffer from numerical artifacts like nonphysical mass transfer along the
solid wall, which is crucial for modeling imbibition-type problems. The article
also proposes an approach to model inflow and outflow boundaries with the color
gradient method by generalizing the regularized boundary conditions. The
numerical framework is first validated for three-dimensional (3D) stationary
state (Jurin's law) and time-dependent (Washburn's law and capillary waves)
problems. Then, the usefulness of the method for practical problems of pore-scale
flow imbibition and drainage in porous media is demonstrated. Through the
simulation of nonwetting displacement in two-dimensional random porous media
networks, we show that the model properly reproduces three main invasion regimes
(stable displacement, capillary fingering, and viscous fingering) as well as the
saturating zone transition between these regimes. Finally, the ability to
simulate immiscible two-component flow imbibition and drainage is validated, with
excellent results, by numerical simulations in a Berea sandstone, a frequently
used benchmark case used in this field, using a complex geometry that originates
from a 3D scan of a porous sandstone. The methods presented in this article were
implemented in the open-source PALABOS library, a general C++ matrix-based
library well adapted for massive fluid flow parallel computation.
PMID- 28415303
TI - Generic patterns in the evolution of urban water networks: Evidence from a large
Asian city.
AB - We examine high-resolution urban infrastructure data using every pipe for the
water distribution network (WDN) and sanitary sewer network (SSN) in a large
Asian city (~4 million residents) to explore the structure as well as the spatial
and temporal evolution of these infrastructure networks. Network data were
spatially disaggregated into multiple subnets to examine intracity topological
differences for functional zones of the WDN and SSN, and time-stamped SSN data
were examined to understand network evolution over several decades as the city
expanded. Graphs were generated using a dual-mapping technique (Hierarchical
Intersection Continuity Negotiation), which emphasizes the functional attributes
of these networks. Network graphs for WDNs and SSNs are characterized by several
network topological metrics, and a double Pareto (power-law) model approximates
the node-degree distributions of both water infrastructure networks (WDN and
SSN), across spatial and hierarchical scales relevant to urban settings, and
throughout their temporal evolution over several decades. These results indicate
that generic mechanisms govern the networks' evolution, similar to those of scale
free networks found in nature. Deviations from the general topological patterns
are indicative of (1) incomplete establishment of network hierarchies and
functional network evolution, (2) capacity for growth (expansion) or
densification (e.g., in-fill), and (3) likely network vulnerabilities. We discuss
the implications of our findings for the (re-)design of urban infrastructure
networks to enhance their resilience to external and internal threats.
PMID- 28415304
TI - Measurement of the equation of state of solid-density copper heated with laser
accelerated protons.
AB - We present equation of state (EOS) measurements of solid-density copper heated to
5-10 eV. A copper sample was heated isochorically by hydrogen ions accelerated
from an adjacent foil by a high intensity pulsed laser, and probed optically. The
measured temperature and expansion are compared against simulations using the
most up-to-date wide range EOS tables available.
PMID- 28415305
TI - Upper bound for the average entropy production based on stochastic entropy
extrema.
AB - The second law of thermodynamics, which asserts the non-negativity of the average
total entropy production of a combined system and its environment, is a direct
consequence of applying Jensen's inequality to a fluctuation relation. It is also
possible, through this inequality, to determine an upper bound of the average
total entropy production based on the entropies along the most extreme stochastic
trajectories. In this work, we construct an upper bound inequality of the average
of a convex function over a domain whose average is known. When applied to the
various fluctuation relations, the upper bounds of the average total entropy
production are established. Finally, by employing the result of Neri, Roldan, and
Julicher [Phys. Rev. X 7, 011019 (2017)]10.1103/PhysRevX.7.011019, we are able to
show that the average total entropy production is bounded only by the total
entropy production supremum, and vice versa, for a general nonequilibrium
stationary system.
PMID- 28415306
TI - Gaussian white noise as a resource for work extraction.
AB - We show that uncorrelated Gaussian noise can drive a system out of equilibrium
and can serve as a resource from which work can be extracted. We consider an
overdamped particle in a periodic potential with an internal degree of freedom
and a state-dependent friction, coupled to an equilibrium bath. Applying
additional Gaussian white noise drives the system into a nonequilibrium steady
state and causes a finite current if the potential is spatially asymmetric. The
model thus operates as a Brownian ratchet, whose current we calculate explicitly
in three complementary limits. Since the particle current is driven solely by
additive Gaussian white noise, this shows that the latter can potentially perform
work against an external load. By comparing the extracted power to the energy
injection due to the noise, we discuss the efficiency of such a ratchet.
PMID- 28415307
TI - Decoding heat capacity features from the energy landscape.
AB - A general scheme is derived to connect transitions in configuration space with
features in the heat capacity. A formulation in terms of occupation probabilities
for local minima that define the potential energy landscape provides a
quantitative description of how contributions arise from competition between
different states. The theory does not rely on a structural interpretation for the
local minima, so it is equally applicable to molecular energy landscapes and the
landscapes defined by abstract functions. Applications are presented for low
temperature solid-solid transitions in atomic clusters, which involve just a few
local minima with different morphologies, and for cluster melting, which is
driven by the landscape entropy associated with the more numerous high-energy
minima. Analyzing these features in terms of the balance between states with
increasing and decreasing occupation probabilities provides a direct
interpretation of the underlying transitions. This approach enables us to
identify a qualitatively different transition that is caused by a single local
minimum associated with an exceptionally large catchment volume in configuration
space for a machine learning landscape.
PMID- 28415308
TI - Thermal transport in the Fermi-Pasta-Ulam model with long-range interactions.
AB - We study the thermal transport properties of the one-dimensional Fermi-Pasta-Ulam
model (beta type) with long-range interactions. The strength of the long-range
interaction decreases with the (shortest) distance between the lattice sites as
distance^{-delta}, where delta>=0. Two Langevin heat baths at unequal
temperatures are connected to the ends of the one-dimensional lattice via short
range harmonic interactions that drive the system away from thermal equilibrium.
In the nonequilibrium steady state the heat current, thermal conductivity, and
temperature profiles are computed by solving the equations of motion numerically.
It is found that the conductivity kappa has an interesting nonmonotonic
dependence with delta with a maximum at delta=2.0 for this model. Moreover, at
delta=2.0,kappa diverges almost linearly with system size N and the temperature
profile has a negligible slope, as one expects in ballistic transport for an
integrable system. We demonstrate that the nonmonotonic behavior of the
conductivity and the nearly ballistic thermal transport at delta=2.0 obtained
under nonequilibrium conditions can be explained consistently by studying the
variation of largest Lyapunov exponent lambda_{max} with delta, and excess energy
diffusion in the equilibrium microcanonical system.
PMID- 28415310
TI - Structure-properties relation for random networks of fibers with noncircular
cross section.
AB - The mechanical behavior of three-dimensional cross-linked random fiber networks
composed from fibers of noncircular cross section characterized by two principal
moments of inertia is studied in this work. Such fibers store energy in the axial
deformation mode and two bending modes of unequal stiffness. We show that the
torsional stiffness of fibers becomes important as it determines the relative
contribution of the two bending modes to the overall deformation. The scaling of
the small strain modulus with the network parameters is established. The large
strain deformation of these structures is less sensitive to the shape of the
cross section.
PMID- 28415309
TI - Laplacian networks: Growth, local symmetry, and shape optimization.
AB - Inspired by river networks and other structures formed by Laplacian growth, we
use the Loewner equation to investigate the growth of a network of thin fingers
in a diffusion field. We first review previous contributions to illustrate how
this formalism reduces the network's expansion to three rules, which respectively
govern the velocity, the direction, and the nucleation of its growing branches.
This framework allows us to establish the mathematical equivalence between three
formulations of the direction rule, namely geodesic growth, growth that maintains
local symmetry, and growth that maximizes flux into tips for a given amount of
growth. Surprisingly, we find that this growth rule may result in a network
different from the static configuration that optimizes flux into tips.
PMID- 28415311
TI - Understanding quantum work in a quantum many-body system.
AB - Based on previous studies in a single-particle system in both the integrable
[Jarzynski, Quan, and Rahav, Phys. Rev. X 5, 031038 (2015)2160
330810.1103/PhysRevX.5.031038] and the chaotic systems [Zhu, Gong, Wu, and Quan,
Phys. Rev. E 93, 062108 (2016)1539-375510.1103/PhysRevE.93.062108], we study the
the correspondence principle between quantum and classical work distributions in
a quantum many-body system. Even though the interaction and the
indistinguishability of identical particles increase the complexity of the
system, we find that for a quantum many-body system the quantum work distribution
still converges to its classical counterpart in the semiclassical limit. Our
results imply that there exists a correspondence principle between quantum and
classical work distributions in an interacting quantum many-body system,
especially in the large particle number limit, and further justify the definition
of quantum work via two-point energy measurements in quantum many-body systems.
PMID- 28415312
TI - Nonlinear effects in the bounded dust-vortex flow in plasma.
AB - The vortex structures in a cloud of electrically suspended dust in a streaming
plasma constitutes a driven system with a rich nonlinear flow regime.
Experimentally recovered toroidal formations of this system have motivated study
of its volumetrically driven-dissipative vortex flow dynamics using two
dimensional hydrodynamics in the incompressible Navier-Stokes regime. Nonlinear
equilibrium solutions are obtained for this system where a nonuniformly driven
two-dimensional dust flow exhibits distinct regions of localized accelerations
and strong friction caused by stationary fluids at the confining boundaries
resisting the dust flow. In agreement with observations in experiments, it is
demonstrated that the nonlinear effects appear in the limit of small viscosity,
where the primary vortices form scaling with the most dominant spatial scales of
the domain topology and develop separated virtual boundaries along their
periphery. This separation is triggered beyond a critical dust viscosity that
signifies a structural bifurcation. Emergence of uniform vorticity core and
secondary vortices with a newer level of identical dynamics highlights the
applicability of the studied dynamics to gigantic vortex flows, such as the
Jovian great red spot, to microscopic biophysical intracellular activity.
PMID- 28415313
TI - Characterization of phase transitions in a model ecosystem of sessile species.
AB - We consider a model ecosystem of sessile species competing for space. In
particular, we consider the system introduced by Mathiesen et al. [J. Mathiesen,
N. Mitarai, K. Sneppen, and A. Trusina, Phys. Rev. Lett. 107, 188101
(2011)PRLTAO0031-900710.1103/PhysRevLett.107.188101] where species compete
according to a fixed interaction network with links determined by a Bernoulli
process. In the limit of a small introduction rate of new species, the model
exhibits a discontinuous transition from a high-diversity state to a low
diversity state as the interaction probability between species, gamma, is
increased from zero. Here we explore the effects of finite introduction rates and
system size on the phase transition by utilizing efficient parallel computing. We
find that the low state appears for gamma>gamma_{c}. As gamma is increased
further, the high state approaches the low state, suggesting the possibility that
the two states merge at a high gamma. We find that the fraction of time spent in
the high state becomes longer with higher introduction rates, but the
availability of the two states is rather insensitive to the value of the
introduction rate. Furthermore, we establish a relation between the introduction
rate and the system size, which preserves the probability for the system to
remain in the high-diversity state.
PMID- 28415314
TI - Cell-alignment patterns in the collective migration of cells with polarized
adhesion.
AB - Dictyostelium discoideum (Dd) utilizes inhomogeneities in the distribution of
cell-cell adhesion molecules on cell membranes for collective cell migration. A
simple example of an inhomogeneity is a front-side (leading-edge) polarization in
the distribution at the early streaming stage. Experiments have shown that the
polarized cell-cell adhesion induces side-by-side contact between cells [Beug et
al., Nature (London) 274, 445 (1978)NATUAS0028-083610.1038/274445a0]. This result
is counterintuitive, as one would expect cells to align front to front in contact
with each other on the basis of front-side polarization. In this work, we
theoretically examine whether front-side polarization induces side-by-side
contact in collective cell migration. We construct a model for expressing cells
with this polarization based on the two-dimensional cellular Potts model. By a
numerical simulation with this model, we find cell-cell alignment wherein cells
form lateral arrays with side-by-side contacts as observed in the experiments.
PMID- 28415315
TI - Rectification and one-way street for the energy current in boundary-driven
asymmetric quantum spin chains.
AB - Motivated by the demand for efficient quantum devices to engineer energy
transport, we analyze some inhomogeneous quantum spin systems, including XXZ
chains, with magnetization baths at the ends. With a goal of finding general
properties, we study the effects of suitable transformations on the boundary
driven Lindblad master equation associated with the dynamics of the systems. For
asymmetric models with target polarization at the edges or twisted XY boundary
gradients, we show the properties of the steady state, which establish the
features of the energy current irrespective of the system size and the regime of
transport. We show the ubiquitous occurrence of energy rectification and, more
interestingly, of an unusual phenomenon: in the absence of an external magnetic
field, there is a one-way street for the energy current, i.e., the direction of
the energy current does not change as we invert the magnetization baths at the
boundaries. Given the extensiveness of the procedures, which essentially involve
the properties of the Lindblad master equation, our results certainly follow for
other interactions and other boundary conditions. Moreover, our results indicate
graded spin chains as genuine quantum rectifiers.
PMID- 28415316
TI - Spheroidal harmonic expansions for the solution of Laplace's equation for a point
source near a sphere.
AB - We propose a powerful approach to solve Laplace's equation for point sources near
a spherical object. The central new idea is to use prolate spheroidal solid
harmonics, which are separable solutions of Laplace's equation in spheroidal
coordinates, instead of the more natural spherical solid harmonics. Using
electrostatics as an example, we motivate this choice and show that the resulting
series expansions converge much faster. This improvement is discussed in terms of
the singularity of the solution and its analytic continuation. The benefits of
this approach are further illustrated for a specific example: the calculation of
modified decay rates of light emitters close to nanostructures in the quasistatic
approximation. We expect the general approach to be applicable with similar
benefits to the solution of Laplace's equation for other geometries and to other
equations of mathematical physics.
PMID- 28415317
TI - Reorientations of the large-scale flow in turbulent convection in a cube.
AB - Large-eddy simulations of turbulent Rayleigh-Benard convection were conducted for
a fluid of Prandtl number Pr=0.7 confined in a cube, for Rayleigh numbers of
10^{6} and 10^{8}. The model solves the unsteady Navier-Stokes equations under
the Boussinesq approximation, using a dynamic Smagorinsky model with a Lagrangian
averaging technique for the subgrid terms. Under fully developed conditions the
flow topology is characterized by a large-scale circulation (LSC) developing in a
plane containing one of the diagonals of the cell, while two counter-rotating
vortices consequently develop in the other diagonal plane, resulting in a strong
inflow at the horizontal midplane. This flow structure is not static, with the
LSC undergoing nonperiodic reorientations, or switching, between the two diagonal
planes; hence, we supplement the observations of the three-dimensional time
averaged flow structures with single point measurements (time series) to shed
light on the dynamics of the reorientations. For all observations, this switching
results from a lateral rotation of the LSC in which some finite time spent in a
transient state where the large-scale circulation is parallel to one set of side
walls; there are, importantly, no observations consistent with so-called
cessations of the LSC, in which it decays and then reforms in another plane
without such a rotation. The average switching rate for the LSC is in excellent
agreement with the results of Bai et al. [K. Bai, D. Ji, and E. Brown, Phys. Rev.
E 93, 023117 (2016)PLEEE81539-375510.1103/PhysRevE.93.023117].
PMID- 28415318
TI - Effects of spatial and temporal noise on a cubic-autocatalytic reaction-diffusion
model.
AB - We characterize the influence that external noise, with both spatial and temporal
correlations, has on the scale dependence of the reaction parameters of a cubic
autocatalytic reaction diffusion (CARD) system. Interpreting the CARD model as a
primitive reaction scheme for a living system, the results indicate that power
law correlations in environmental fluctuations can either decrease or increase
the rates of nutrient decay and the rate of autocatalysis (replication) on small
spatial and temporal scales.
PMID- 28415319
TI - Footprint geometry and sessile drop resonance.
AB - In this work, we examine experimentally the resonance of a sessile drop with a
square footprint (square drop) on a flat plate. Two families of modal behaviors
are reported. One family is identified with the modes of sessile drops with
circular footprints (circular drop), denoted as "spherical modes." The other
family is associated with Faraday waves on a square liquid bath (square Faraday
waves), denoted as "grid modes." The two families are distinguished based on
their dispersion behaviors. By comparing the occurrence of the modes, we
recognize spherical modes as the characteristic of sessile drops, and grid modes
as the constrained response. Within a broader context, we further discuss the
resonance modes of circular sessile drops and free spherical drops, and we
recognize various modal behaviors as surface waves under different extents of
constraint. From these, we conclude that sessile drops resonate according to how
wave-number selection by footprint geometry and capillarity compete. For square
drops, a dominant effect of footprint constraint leads to grid modes; otherwise,
the drops exhibit spherical modes, the characteristic of sessile drops on flat
plates.
PMID- 28415320
TI - Background scalar-level anisotropy caused by low-wave-number truncation in
turbulent flows.
AB - We rigorously show that the truncation at low wave numbers always leads to
background scalar-level anisotropy at large scales. Neither the resolution nor
the spectral low-pass filter is dominant for this anisotropy, while the shape of
the energy spectrum at low wave numbers is an important influence factor.
Quantitative results are shown to provide references to the statistics in future
postprocessing studies. Also, a simplified analytical model is introduced to
explain the single-mode effects for this anisotropy.
PMID- 28415321
TI - Sedimentation equilibrium of magnetic nanoparticles with strong dipole-dipole
interactions.
AB - Langevin dynamics simulation is used to study the suspension of interacting
magnetic nanoparticles (dipolar spheres) in a zero applied magnetic field and in
the presence of a gravitational (centrifugal) field. A particular emphasis is
placed on the equilibrium vertical distribution of particles in the infinite
horizontal slab. An increase in the dipolar coupling constant lambda (the ratio
of dipole-dipole interaction energy to thermal energy) from zero to seven units
causes an increase in the particle segregation coefficient by several orders of
magnitude. The effect of anisotropic dipole-dipole interactions on the
concentration profile of particles is the same as that of the isotropic van der
Waals attraction modeled by the Lennard-Jones potential. In both cases, the area
with a high-density gradient separating the area with high and low particle
concentration is formed on the profiles. Qualitative difference between two
potentials manifests itself only in the fact that in the absence of a
gravitational field the dipole-dipole interactions do not lead to the "gas
liquid" phase transition: no separation of the system into weakly and highly
concentrated phases is observed. At high particle concentration and at large
values of lambda, the orientational ordering of magnetic dipoles takes place in
the system. Magnetic structure of the system strongly depends on the imposed
boundary conditions. Spontaneous magnetization occurs in the infinite horizontal
slab (i.e., in the rectangular cell with two-dimensional periodic boundary
conditions). Replacement of the infinite slab by the finite-size hard-wall
vertical cylinder leads to the formation of azimuthal (vortex-like) order. The
critical values of the coupling constant corresponding to the transition into an
ordered state are very close for two geometries.
PMID- 28415322
TI - Thermal rectification in mass-graded next-nearest-neighbor Fermi-Pasta-Ulam
lattices.
AB - We study the thermal rectification efficiency, i.e., quantification of asymmetric
heat flow, of a one-dimensional mass-graded anharmonic oscillator Fermi-Pasta
Ulam lattice both with nearest-neighbor (NN) and next-nearest-neighbor (NNN)
interactions. The system presents a maximum rectification efficiency for a very
precise value of the parameter that controls the coupling strength of the NNN
interactions, which also optimizes the rectification figure when its dependence
on mass asymmetry and temperature differences is considered. The origin of the
enhanced rectification is the asymmetric local heat flow response as the heat
reservoirs are swapped when a finely tuned NNN contribution is taken into
account. A simple theoretical analysis gives an estimate of the optimal NNN
coupling in excellent agreement with our simulation results.
PMID- 28415324
TI - Scale dependence of multiplier distributions for particle concentration,
enstrophy, and dissipation in the inertial range of homogeneous turbulence.
AB - Turbulent flows preferentially concentrate inertial particles depending on their
stopping time or Stokes number, which can lead to significant spatial variations
in the particle concentration. Cascade models are one way to describe this
process in statistical terms. Here, we use a direct numerical simulation (DNS)
dataset of homogeneous, isotropic turbulence to determine probability
distribution functions (PDFs) for cascade multipliers, which determine the ratio
by which a property is partitioned into subvolumes as an eddy is envisioned to
decay into smaller eddies. We present a technique for correcting effects of small
particle numbers in the statistics. We determine multiplier PDFs for particle
number, flow dissipation, and enstrophy, all of which are shown to be scale
dependent. However, the particle multiplier PDFs collapse when scaled with an
appropriately defined local Stokes number. As anticipated from earlier works,
dissipation and enstrophy multiplier PDFs reach an asymptote for sufficiently
small spatial scales. From the DNS measurements, we derive a cascade model that
is used it to make predictions for the radial distribution function (RDF) for
arbitrarily high Reynolds numbers, Re, finding good agreement with the
asymptotic, infinite Re inertial range theory of Zaichik and Alipchenkov [New J.
Phys. 11, 103018 (2009)NJOPFM1367-263010.1088/1367-2630/11/10/103018]. We discuss
implications of these results for the statistical modeling of the turbulent
clustering process in the inertial range for high Reynolds numbers inaccessible
to numerical simulations.
PMID- 28415323
TI - Variable species densities are induced by volume exclusion interactions upon
domain growth.
AB - In this work we study the effect of domain growth on spatial correlations in
agent populations containing multiple species. This is important as heterogenous
cell populations are ubiquitous during the embryonic development of many species.
We have previously shown that the long-term behavior of an agent population
depends on the way in which domain growth is implemented. We extend this work to
show that, depending on the way in which domain growth is implemented, different
species dominate in multispecies simulations. Continuum approximations of the
lattice-based model that ignore spatial correlations cannot capture this
behavior, while those that explicitly account for spatial correlations can. The
results presented here show that the precise mechanism of domain growth can
determine the long-term behavior of multispecies populations and, in certain
circumstances, establish spatially varying species densities.
PMID- 28415325
TI - Modulation of unpolarized light in planar-aligned subwavelength-pitch deformed
helix ferroelectric liquid crystals.
AB - We study the electro-optic properties of subwavelength-pitch deformed-helix
ferroelectric liquid crystals (DHFLC) illuminated with unpolarized light. In the
experimental setup based on the Mach-Zehnder interferometer, it was observed that
the reference and the sample beams being both unpolarized produce the
interference pattern which is insensitive to rotation of in-plane optical axes of
the DHFLC cell. We find that the field-induced shift of the interference fringes
can be described in terms of the electrically dependent Pancharatnam relative
phase determined by the averaged phase shift, whereas the visibility of the
fringes is solely dictated by the phase retardation.
PMID- 28415326
TI - Numerical study of one-dimensional compression of granular materials. II. Elastic
moduli, stresses, and microstructure.
AB - The elastic moduli of a transversely isotropic model granular material, made of
slightly polydisperse elastic-frictional spherical beads, in equilibrium along a
one-dimensional (oedometric) compression path, as described in the companion
paper [M. H. Khalili et al., Phys. Rev. E 95, 032907
(2017)]10.1103/PhysRevE.95.032907, are investigated by numerical simulations. The
relations of the five independent moduli to stresses, density, coordination
number, fabric and force anisotropies are studied for different internal material
states along the oedometric loading path. It is observed that elastic moduli, as
in isotropic packs, are primarily determined by the coordination number, with
anomalously small shear moduli in poorly coordinated systems, whatever their
density. Such states also exhibit faster increasing moduli in compression, and
larger off-diagonal moduli and Poisson ratios. Anisotropy affects the
longitudinal moduli C_{11} in the axial direction and C_{22} in the transverse
directions, and the shear modulus in the transverse plane C_{44}, more than the
shear modulus in a plane containing the axial direction C_{55}. The results are
compared to available experiments on anisotropic bead packs, revealing, despite
likely differences in internal states, a very similar range of stiffness level
(linked to coordination), and semiquantitative agreement as regards the influence
of anisotropy. Effective medium theory (the Voigt approach) provides quite
inaccurate predictions of the moduli. It also significantly underestimates ratios
C_{11}/C_{22} (varying between 1 and 2.2) and C_{55}/C_{44} (varying from 1 to
1.6), which characterize elastic anisotropy, except in relatively weakly
anisotropic states. The bulk modulus for isotropic compression and the compliance
corresponding to stress increments proportional to the previous stress values are
the only elastic coefficients to be correctly estimated by available predictive
relations. We discuss the influences of fabric and force anisotropies onto
elastic anisotropy, showing in particular that the former dominates in sample
series that are directly assembled in anisotropic configurations and keep a
roughly constant lateral to axial stress ratio under compression.
PMID- 28415327
TI - Facets on the convex hull of d-dimensional Brownian and Levy motion.
AB - For stationary, homogeneous Markov processes (viz., Levy processes, including
Brownian motion) in dimension d>=3, we establish an exact formula for the average
number of (d-1)-dimensional facets that can be defined by d points on the
process's path. This formula defines a universality class in that it is
independent of the increments' distribution, and it admits a closed form when
d=3, a case which is of particular interest for applications in biophysics,
chemistry, and polymer science. We also show that the asymptotical average number
of facets behaves as ~2[ln(T/Deltat)]^{d-1}, where T is the total
duration of the motion and Deltat is the minimum time lapse separating points
that define a facet.
PMID- 28415328
TI - Asymmetric transmission of sound wave in cavitating liquids.
AB - Two modes of the asymmetric sound transmission are observed experimentally in a
one-dimensional system composed of coupled two layers of liquids. Their
cavitation thresholds are different from each other. When the sound wave
propagates from the high-threshold liquid to the low-threshold liquid, the two
liquids can avoid the cavitation for a medium driving pressure. When it
propagates from the low-threshold liquid to the high-threshold liquid, however,
the low-threshold liquid can be cavitated by the same driving pressure, though
the high-threshold liquid remains uncavitated. Therefore, there is a sound
transmission asymmetry, or sound rectification in this double-layer liquid.
Furthermore, when the system is driven by a high pressure, cavitation can take
place in both high- and low-threshold liquids in the sound transmission from the
high-threshold liquid to the low-threshold liquid, but only the low-threshold
liquid can be cavitated in the opposite transmission. This mechanism gives an
asymmetry with reversed rectifying direction. The efficiency of rectification is
related to the driving sound pressure and the cavitation thresholds of the two
liquids based on experimental results. Finally, the experimental observations are
reproduced by the numerical simulation based on the modified two-phase fluid
mechanics.
PMID- 28415329
TI - Kardar-Parisi-Zhang equation with short-range correlated noise: Emergent
symmetries and nonuniversal observables.
AB - We investigate the stationary-state fluctuations of a growing one-dimensional
interface described by the Kardar-Parisi-Zhang (KPZ) dynamics with a noise
featuring smooth spatial correlations of characteristic range xi. We employ
nonperturbative functional renormalization group methods to resolve the
properties of the system at all scales. We show that the physics of the standard
(uncorrelated) KPZ equation emerges on large scales independently of xi.
Moreover, the renormalization group flow is followed from the initial condition
to the fixed point, that is, from the microscopic dynamics to the large-distance
properties. This provides access to the small-scale features (and their
dependence on the details of the noise correlations) as well as to the universal
large-scale physics. In particular, we compute the kinetic energy spectrum of the
stationary state as well as its nonuniversal amplitude. The latter is
experimentally accessible by measurements at large scales and retains a signature
of the microscopic noise correlations. Our results are compared to previous
analytical and numerical results from independent approaches. They are in
agreement with direct numerical simulations for the kinetic energy spectrum as
well as with the prediction, obtained with the replica trick by Gaussian
variational method, of a crossover in xi of the nonuniversal amplitude of this
spectrum.
PMID- 28415330
TI - Performance of a quantum heat engine at strong reservoir coupling.
AB - We study a quantum heat engine at strong coupling between the system and the
thermal reservoirs. Exploiting a collective coordinate mapping, we incorporate
system-reservoir correlations into a consistent thermodynamic analysis, thus
circumventing the usual restriction to weak coupling and vanishing correlations.
We apply our formalism to the example of a quantum Otto cycle, demonstrating that
the performance of the engine is diminished in the strong coupling regime with
respect to its weakly coupled counterpart, producing a reduced net work output
and operating at a lower energy conversion efficiency. We identify costs imposed
by sudden decoupling of the system and reservoirs around the cycle as being
primarily responsible for the diminished performance, and we define an
alternative operational procedure which can partially recover the work output and
efficiency. More generally, the collective coordinate mapping holds considerable
promise for wider studies of thermodynamic systems beyond weak reservoir
coupling.
PMID- 28415331
TI - Transition radiation at the boundary of a chiral isotropic medium.
AB - This study analyzes the radiation produced by a point charge intersecting the
interface between a vacuum and a chiral isotropic medium. We deduce analytical
expressions for the Fourier components of an electromagnetic field in both vacuum
and medium for arbitrary charge velocity. The main focus is on investigating the
far field in a vacuum. The distinguishing feature of the interface with a chiral
isotropic medium is that the field in the vacuum area contains both
copolarization (coinciding with the polarization of the self-field of a charge)
and cross-polarization (orthogonal to the polarization of the self-field). Using
a saddle-point approach, we obtain asymptotic representations for the field
components in the far-field zone for typical frequency ranges of the Condon model
of the chiral medium. We note that a so-called lateral wave is generated in a
vacuum for certain parameters. The main contribution to the radiation at large
distances is presented by two (co- and cross-) spherical waves of transition
radiation. These waves are coherent and result in a total spherical wave with
elliptical polarization, with the polarization coefficient being determined by
the chirality of the medium. We present typical radiation patterns and ellipses
of polarization.
PMID- 28415332
TI - Numerical simulations of Ising spin glasses with free boundary conditions: The
role of droplet excitations and domain walls.
AB - The relative importance of the contributions of droplet excitations and domain
walls on the ordering of short-range Edwards-Anderson spin glasses in three and
four dimensions is studied. We compare the spin overlap distribution functions of
periodic and free boundary conditions using population annealing Monte Carlo. For
system sizes up to about 1000 spins, spin glasses show nontrivial spin overlap
distributions. Periodic boundary conditions may trap diffusive domain walls which
can contribute to small spin overlaps, and the other contribution is the
existence of low-energy droplet excitations within the system. We use free
boundary conditions to minimize domain-wall effects, and show that low-energy
droplet excitations are the major contribution to small overlaps in numerical
simulations. Free boundary conditions has stronger finite-size effects, and is
likely to have the same thermodynamic limit with periodic boundary conditions.
PMID- 28415333
TI - Melting of a nonequilibrium vortex crystal in a fluid film with polymers: Elastic
versus fluid turbulence.
AB - We perform a direct numerical simulation of the forced, incompressible two
dimensional Navier-Stokes equation coupled with the FENE-P equations for the
polymer-conformation tensor. The forcing is such that, without polymers and at
low Reynolds numbers Re, the film attains a steady state that is a square lattice
of vortices and antivortices. We find that, as we increase the Weissenberg number
Wi, a sequence of nonequilibrium phase transitions transforms this lattice, first
to spatially distorted, but temporally steady, crystals and then to a sequence of
crystals that oscillate in time, periodically, at low Wi, and quasiperiodically,
for slightly larger Wi. Finally, the system becomes disordered and displays
spatiotemporal chaos and elastic turbulence. We then obtain the nonequilibrium
phase diagram for this system, in the Wi-Omega plane, where Omega?Re, and show
that (a) the boundary between the crystalline and turbulent phases has a
complicated, fractal-type character and (b) the Okubo-Weiss parameter Lambda
provides us with a natural measure for characterizing the phases and transitions
in this diagram.
PMID- 28415334
TI - Quantum Jarzynski equality of measurement-based work extraction.
AB - Many studies of quantum-size heat engines assume that the dynamics of an internal
system is unitary and that the extracted work is equal to the energy loss of the
internal system. Both assumptions, however, should be under scrutiny. In the
present paper, we analyze quantum-scale heat engines, employing the measurement
based formulation of the work extraction recently introduced by Hayashi and
Tajima [M. Hayashi and H. Tajima, arXiv:1504.06150]. We first demonstrate the
inappropriateness of the unitary time evolution of the internal system (namely,
the first assumption above) using a simple two-level system; we show that the
variance of the energy transferred to an external system diverges when the
dynamics of the internal system is approximated to a unitary time evolution.
Second, we derive the quantum Jarzynski equality based on the formulation of
Hayashi and Tajima as a relation for the work measured by an external macroscopic
apparatus. The right-hand side of the equality reduces to unity for "natural"
cyclic processes but fluctuates wildly for noncyclic ones, exceeding unity often.
This fluctuation should be detectable in experiments and provide evidence for the
present formulation.
PMID- 28415335
TI - Effectively explore metastable states of proteins by adaptive nonequilibrium
driving simulations.
AB - Nonequilibrium drivings applied in molecular dynamics (MD) simulations can
efficiently extend the visiting range of protein conformations, but might compel
systems to go far away from equilibrium and thus mainly explore irrelevant
conformations. Here we propose a general method, called adaptive nonequilibrium
simulation (ANES), to automatically adjust the external driving on the fly, based
on the feedback of the short-time average response of system. Thus, the ANES
approximately keeps the local equilibrium but efficiently accelerates the global
motion. We illustrate the capability of the ANES in highly efficiently exploring
metastable conformations in the deca-alanine peptide and find that the 0.2-MUs
ANES approximately captures the important states and folding and unfolding
pathways in the HP35 solution by comparing with the result of the recent 398-MUs
equilibrium MD simulation on Anton [S. Piana et al., Proc. Natl. Acad. Sci. USA
109, 17845 (2012)PNASA60027-842410.1073/pnas.1201811109].
PMID- 28415336
TI - Arrays of two-state stochastic oscillators: Roles of tail and range of
interactions.
AB - We study the role of the tail and the range of interaction in a spatially
structured population of two-state on-off units governed by Markovian transition
rates. The coupling among the oscillators is evidenced by the dependence of the
transition rates of each unit on the states of the units to which it is coupled.
Tuning the tail or range of the interactions, we observe a transition from an
ordered global state (long-range interactions) to a disordered one (short-range
interactions). Depending on the interaction kernel, the transition may be smooth
(second order) or abrupt (first order). We analyze the transient, which may
present different routes to the steady state with vastly different time scales.
PMID- 28415337
TI - Mean-squared-displacement statistical test for fractional Brownian motion.
AB - Anomalous diffusion in crowded fluids, e.g., in cytoplasm of living cells, is a
frequent phenomenon. A common tool by which the anomalous diffusion of a single
particle can be classified is the time-averaged mean square displacement (TAMSD).
A classical mechanism leading to the anomalous diffusion is the fractional
Brownian motion (FBM). A validation of such process for single-particle tracking
data is of great interest for experimentalists. In this paper we propose a
rigorous statistical test for FBM based on TAMSD. To this end we analyze the
distribution of the TAMSD statistic, which is given by the generalized chi
squared distribution. Next, we study the power of the test by means of Monte
Carlo simulations. We show that the test is very sensitive for changes of the
Hurst parameter. Moreover, it can easily distinguish between two models of
subdiffusion: FBM and continuous-time random walk.
PMID- 28415338
TI - Elastic anisotropy effects on the electrical responses of a thin sample of
nematic liquid crystal.
AB - The electrical responses of a nematic liquid crystal cell are investigated by
means of the elastic continuum theory. The nematic medium is considered as a
parallel circuit of a resistance and a capacitance and the electric current
profile across the sample is determined as a function of the elastic constants.
In the reorientation process of the nematic director, the resistance and
capacitance of the sample are determined by taking into account the elastic
anisotropy. A nonmonotonic profile for the current is observed in which a minimum
value of the current may be used to estimate the elastic constants values. This
scenario suggests a theoretical method to determine the values of the bulk
elastic constants in a single planar aligned cell just by changing the direction
of applied electrical field and measuring the resulting electrical current.
PMID- 28415339
TI - Fast forward to the classical adiabatic invariant.
AB - We show how the classical action, an adiabatic invariant, can be preserved under
nonadiabatic conditions. Specifically, for a time-dependent Hamiltonian
H=p^{2}/2m+U(q,t) in one degree of freedom, and for an arbitrary choice of action
I_{0}, we construct a so-called fast-forward potential energy function
V_{FF}(q,t) that, when added to H, guides all trajectories with initial action
I_{0} to end with the same value of action. We use this result to construct a
local dynamical invariant J(q,p,t) whose value remains constant along these
trajectories. We illustrate our results with numerical simulations. Finally, we
sketch how our classical results may be used to design approximate quantum
shortcuts to adiabaticity.
PMID- 28415340
TI - Development of kinks in car-following models.
AB - Many car-following models of traffic flow admit the possibility of absolute
stability, a situation in which uniform traffic flow at any spacing is linearly
stable. Near the threshold of absolute stability, these models can often be
reduced to a modified Korteweg-deVries (mKdV) equation plus small corrections.
The hyperbolic-tangent "kink" solutions of the mKdV equation are usually of
particular interest, as they represent transition zones between regions of
different traffic spacings. Solvability analysis is believed to show that only a
single member of the one-parameter family of kink solutions is preserved by the
correction terms, and this is interpreted as a kind of selection. We show,
however, that the usual solvability calculation rests on an unstated, unjustified
assumption, and that without this assumption it merely gives a first-order
correction to the relation between the traffic spacings far behind and far ahead
of the kink, rather than any kind of "selection" criterion for the family of kink
solutions. On the other hand, we display a two-parameter family of traveling wave
solutions of the mKdV equation, which describe regions of one traffic spacing
embedded in traffic of a different spacing; this family includes the kink
solutions as a limiting case. We carry out a multiple-time-scales calculation and
find conditions under which the inclusions decay, conditions that lead to a
selected inclusion, and conditions for which the inclusion evolves into a pair of
kinks.
PMID- 28415341
TI - Influence of orientation on the evolution of small perturbations in compressible
shear layers with inflection points.
AB - We investigate the influence of orientation on the evolution of small
perturbations in compressible shear layers with inflection points. By using
linear analysis, we demonstrate that perturbations along the shear plane are most
affected by compressibility. The influence of compressibility gradually
diminishes with increasing obliqueness of the perturbations with respect to the
shear plane. It is demonstrated that the effective gradient Mach number is an
appropriate compressibility parameter. We establish that spanwise perturbations,
orthogonal to the shear plane, are impervious to compressibility effects. Direct
numerical simulations of compressible mixing layers subject to the perturbations
at various obliqueness angles verify the analytical findings.
PMID- 28415342
TI - Griffiths phase on hierarchical modular networks with small-world edges.
AB - The Griffiths phase has been proposed to induce a stretched critical regime that
facilitates self-organizing of brain networks for optimal function. This phase
stems from the intrinsic structural heterogeneity of brain networks, i.e., the
hierarchical modular structure. In this work, the Griffiths phase is studied in
modified hierarchical networks with small-world connections based on the 3
regular Hanoi network. Through extensive simulations, the hierarchical level
dependent inter-module wiring probabilities are identified to determine the
emergence of the Griffiths phase. Numerical results and the complementary
spectral analysis of the relevant networks can be helpful for a deeper
understanding of the essential structural characteristics of finite-dimensional
networks to support the Griffiths phase.
PMID- 28415343
TI - Normal vibrational modes of phospholipid bilayers observed by low-frequency Raman
scattering.
AB - Low-frequency Raman spectra of multilamellar vesicles made either of 1-palmitoyl
2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dipalmitoyl-sn-glycero-3
phosphocholine (DPPC) have been studied in a wide temperature range. Below 0^{?}C
two peaks are found at frequencies around 8-9 and 14-17cm^{-1} and attributed to
the normal vibrational modes of the phospholipid bilayer, which are determined by
the bilayer thickness and stiffness (elastic modulus). The spectral positions of
the peaks depend on the temperature and the bilayer composition. It is suggested
that the ratio of the intensities of the first and second peaks can serve as a
measure of the interleaflet elastic coupling. The addition of cholesterol to the
phospholipid bilayer leads to peak shift and broadening, which may be assigned to
the composition heterogeneities commonly attributed to the lipid raft formation.
PMID- 28415344
TI - Simple noise-reduction method based on nonlinear forecasting.
AB - Nonparametric detrending or noise reduction methods are often employed to
separate trends from noisy time series when no satisfactory models exist to fit
the data. However, conventional noise reduction methods depend on subjective
choices of smoothing parameters. Here we present a simple multivariate noise
reduction method based on available nonlinear forecasting techniques. These are
in turn based on state-space reconstruction for which a strong theoretical
justification exists for their use in nonparametric forecasting. The noise
reduction method presented here is conceptually similar to Schreiber's noise
reduction method using state-space reconstruction. However, we show that
Schreiber's method has a minor flaw that can be overcome with forecasting.
Furthermore, our method contains a simple but nontrivial extension to
multivariate time series. We apply the method to multivariate time series
generated from the Van der Pol oscillator, the Lorenz equations, the Hindmarsh
Rose model of neuronal spiking activity, and to two other univariate real-world
data sets. It is demonstrated that noise reduction heuristics can be objectively
optimized with in-sample forecasting errors that correlate well with actual noise
reduction errors.
PMID- 28415345
TI - Deterministic extinction by mixing in cyclically competing species.
AB - We consider a cyclically competing species model on a ring with global mixing at
finite rate, which corresponds to the well-known Lotka-Volterra equation in the
limit of infinite mixing rate. Within a perturbation analysis of the model from
the infinite mixing rate, we provide analytical evidence that extinction occurs
deterministically at sufficiently large but finite values of the mixing rate for
any species number N>=3. Further, by focusing on the cases of rather small
species numbers, we discuss numerical results concerning the trajectories toward
such deterministic extinction, including global bifurcations caused by changing
the mixing rate.
PMID- 28415346
TI - Synchronization of oscillators through time-shifted common inputs.
AB - Shared upstream dynamical processes are frequently the source of common inputs in
various physical and biological systems. However, due to finite signal
transmission speeds and differences in the distance to the source, time shifts
between otherwise common inputs are unavoidable. Since common inputs can be a
source of correlation between the elements of multi-unit dynamical systems,
regardless of whether these elements are directly connected with one another or
not, it is of importance to understand their impact on synchronization. As a
canonical model that is representative for a variety of different dynamical
systems, we study limit-cycle oscillators that are driven by stochastic time
shifted common inputs. We show that if the oscillators are coupled, time shifts
in stochastic common inputs do not simply shift the distribution of the phase
differences, but rather the distribution actually changes as a result. The best
synchronization is therefore achieved at a precise intermediate value of the time
shift, which is due to a resonance-like effect with the most probable phase
difference that is determined by the deterministic dynamics.
PMID- 28415347
TI - Collisional model of energy dissipation in three-dimensional granular impact.
AB - We study the dynamic process occurring when a granular assembly is displaced by a
solid impactor. The momentum transfer from the impactor to the target is shown to
occur through sporadic, normal collisions of high force carrying grains at the
intruder surface. We therefore describe the stopping force of the impact through
a collisional-based model. To verify the model in impact experiments, we
determine the forces acting on an intruder decelerating through a dense granular
medium by using high-speed imaging of its trajectory. By varying the intruder
shape and granular target, intruder-grain interactions are inferred from the
consequent path. As a result, we connect the drag to the effect of intruder shape
and grain density based on a proposed collisional model.
PMID- 28415348
TI - Delineating parameter unidentifiabilities in complex models.
AB - Scientists use mathematical modeling as a tool for understanding and predicting
the properties of complex physical systems. In highly parametrized models there
often exist relationships between parameters over which model predictions are
identical, or nearly identical. These are known as structural or practical
unidentifiabilities, respectively. They are hard to diagnose and make reliable
parameter estimation from data impossible. They furthermore imply the existence
of an underlying model simplification. We describe a scalable method for
detecting unidentifiabilities, as well as the functional relations defining them,
for generic models. This allows for model simplification, and appreciation of
which parameters (or functions thereof) cannot be estimated from data. Our
algorithm can identify features such as redundant mechanisms and fast time-scale
subsystems, as well as the regimes in parameter space over which such
approximations are valid. We base our algorithm on a quantification of regional
parametric sensitivity that we call 'multiscale sloppiness'. Traditionally, the
link between parametric sensitivity and the conditioning of the parameter
estimation problem is made locally, through the Fisher information matrix. This
is valid in the regime of infinitesimal measurement uncertainty. We demonstrate
the duality between multiscale sloppiness and the geometry of confidence regions
surrounding parameter estimates made where measurement uncertainty is non
negligible. Further theoretical relationships are provided linking multiscale
sloppiness to the likelihood-ratio test. From this, we show that a local
sensitivity analysis (as typically done) is insufficient for determining the
reliability of parameter estimation, even with simple (non)linear systems. Our
algorithm can provide a tractable alternative. We finally apply our methods to a
large-scale, benchmark systems biology model of necrosis factor (NF)-kappaB,
uncovering unidentifiabilities.
PMID- 28415349
TI - Decorrelation correction for nanoparticle tracking analysis of dilute
polydisperse suspensions in bulk flow.
AB - Nanoparticle tracking analysis, a multiprobe single particle tracking technique,
is a widely used method to quickly determine the concentration and size
distribution of colloidal particle suspensions. Many popular tools remove non
Brownian components of particle motion by subtracting the ensemble-average
displacement at each time step, which is termed dedrifting. Though critical for
accurate size measurements, dedrifting is shown here to introduce significant
biasing error and can fundamentally limit the dynamic range of particle size that
can be measured for dilute heterogeneous suspensions such as biological
extracellular vesicles. We report a more accurate estimate of particle mean
square displacement, which we call decorrelation analysis, that accounts for
correlations between individual and ensemble particle motion, which are
spuriously introduced by dedrifting. Particle tracking simulation and
experimental results show that this approach more accurately determines particle
diameters for low-concentration polydisperse suspensions when compared with
standard dedrifting techniques.
PMID- 28415350
TI - Simple unified view of branching process statistics: Random walks in balanced
logarithmic potentials.
AB - We revisit the problem of deriving the mean-field values of avalanche exponents
in systems with absorbing states. These are well known to coincide with those of
unbiased branching processes. Here we show that for at least four different
universality classes (directed percolation, dynamical percolation, the voter
model or compact directed percolation class, and the Manna class of stochastic
sandpiles) this common result can be obtained by mapping the corresponding
Langevin equations describing each of them into a random walker confined to the
origin by a logarithmic potential. We report on the emergence of nonuniversal
continuously varying exponent values stemming from the presence of small external
driving - that might induce avalanche merging - that, to the best of our
knowledge, has not been noticed in the past. Many of the other results derived
here appear in the literature as independently derived for individual
universality classes or for the branching process itself. Still, we believe that
a simple and unified perspective as the one presented here can help (1) clarify
the overall picture, (2) underline the superuniversality of the behavior as well
as the dependence on external driving, and (3) avoid the common existing
confusion between unbiased branching processes (equivalent to a random walker in
a balanced logarithmic potential) and standard (unconfined) random walkers.
PMID- 28415351
TI - Gross-Pitaevski map as a chaotic dynamical system.
AB - The Gross-Pitaevski map is a discrete time, split-operator version of the Gross
Pitaevski dynamics in the circle, for which exponential instability has been
recently reported. Here it is studied as a classical dynamical system in its own
right. A systematic analysis of Lyapunov exponents exposes strongly chaotic
behavior. Exponential growth of energy is then shown to be a direct consequence
of rotational invariance and for stationary solutions the full spectrum of
Lyapunov exponents is analytically computed. The present analysis includes the
"resonant" case, when the free rotation period is commensurate to 2pi, and the
map has countably many constants of the motion. Except for lowest-order
resonances, this case exhibits an integrable-chaotic transition.
PMID- 28415352
TI - Self-averaging in the random two-dimensional Ising ferromagnet.
AB - We study sample-to-sample fluctuations in a critical two-dimensional Ising model
with quenched random ferromagnetic couplings. Using replica calculations in the
renormalization group framework we derive explicit expressions for the
probability distribution function of the critical internal energy and for the
specific heat fluctuations. It is shown that the disorder distribution of
internal energies is Gaussian, and the typical sample-to-sample fluctuations as
well as the average value scale with the system size L like ~Llnln(L). In
contrast, the specific heat is shown to be self-averaging with a distribution
function that tends to a delta peak in the thermodynamic limit L->infinity. While
previously a lack of self-averaging was found for the free energy, we here obtain
results for quantities that are directly measurable in simulations, and
implications for measurements in the actual lattice system are discussed.
PMID- 28415353
TI - Noise-induced symmetry breaking far from equilibrium and the emergence of
biological homochirality.
AB - The origin of homochirality, the observed single-handedness of biological amino
acids and sugars, has long been attributed to autocatalysis, a frequently assumed
precursor for early life self-replication. However, the stability of homochiral
states in deterministic autocatalytic systems relies on cross-inhibition of the
two chiral states, an unlikely scenario for early life self-replicators. Here we
present a theory for a stochastic individual-level model of autocatalytic
prebiotic self-replicators that are maintained out of thermal equilibrium.
Without chiral inhibition, the racemic state is the global attractor of the
deterministic dynamics, but intrinsic multiplicative noise stabilizes the
homochiral states. Moreover, we show that this noise-induced bistability is
robust with respect to diffusion of molecules of opposite chirality, and systems
of diffusively coupled autocatalytic chemical reactions synchronize their final
homochiral states when the self-replication is the dominant production mechanism
for the chiral molecules. We conclude that nonequilibrium autocatalysis is a
viable mechanism for homochirality, without imposing additional nonlinearities
such as chiral inhibition.
PMID- 28415354
TI - Stochastic resonance across bifurcation cascades.
AB - The classical setting of stochastic resonance is extended to account for
parameter variations leading to transitions between a unique stable state,
bistability, and multistability regimes, across singularities of various kinds.
Analytic expressions for the amplitude and the phase of the response in terms of
key parameters are obtained. The conditions for optimal responses are derived in
terms of the bifurcation parameter, the driving frequency, and the noise
strength.
PMID- 28415355
TI - Numerical study of continuous and discontinuous dynamical phase transitions for
boundary-driven systems.
AB - The existence and search for thermodynamic phase transitions is of unfading
interest. In this paper, we present numerical evidence of dynamical phase
transitions occurring in boundary-driven systems with a constrained integrated
current. It is shown that certain models exhibit a discontinuous transition
between two different density profiles and a continuous transition between a time
independent and a time-dependent profile. We also verified that the Kipnis
Marchioro-Presutti model exhibits no phase transitions in a range much larger
than previously explored.
PMID- 28415356
TI - Nonspherical liquid droplet falling in air.
AB - The dynamics of an initially nonspherical liquid droplet falling in air under the
action of gravity is investigated via three-dimensional numerical simulations of
the Navier-Stokes and continuity equations in the inertial regime. The surface
tension is considered to be high enough so that a droplet does not undergo
breakup. Vertically symmetric oscillations which decay with time are observed for
low inertia. The amplitude of these oscillations increases for high Gallilei
numbers and the shape asymmetry in the vertical direction becomes prominent. The
reason for this asymmetry has been attributed to the higher aerodynamic inertia.
Moreover, even for large inertia, no path deviations or oscillations are
observed.
PMID- 28415357
TI - Dense crystalline packings of ellipsoids.
AB - An ellipsoid, the simplest nonspherical shape, has been extensively used as a
model for elongated building blocks for a wide spectrum of molecular, colloidal,
and granular systems. Yet the densest packing of congruent hard ellipsoids, which
is intimately related to the high-density phase of many condensed matter systems,
is still an open problem. We discover an unusual family of dense crystalline
packings of self-dual ellipsoids (ratios of the semiaxes alpha:sqrt[alpha]:1),
containing 24 particles with a quasi-square-triangular (SQ-TR) tiling arrangement
in the fundamental cell. The associated packing density phi exceeds that of the
densest known SM2 crystal [ A. Donev et al., Phys. Rev. Lett. 92, 255506
(2004)10.1103/PhysRevLett.92.255506] for aspect ratios alpha in (1.365, 1.5625),
attaining a maximal phi~0.75806... at alpha=93/64. We show that the SQ-TR phase
derived from these dense packings is thermodynamically stable at high densities
over the aforementioned alpha range and report a phase diagram for self-dual
ellipsoids. The discovery of the SQ-TR crystal suggests organizing principles for
nonspherical particles and self-assembly of colloidal systems.
PMID- 28415358
TI - Hamiltonian and Godunov structures of the Grad hierarchy.
AB - The time evolution governed by the Boltzmann kinetic equation is compatible with
mechanics and thermodynamics. The former compatibility is mathematically
expressed in the Hamiltonian and Godunov structures, the latter in the structure
of gradient dynamics guaranteeing the growth of entropy and consequently the
approach to equilibrium. We carry all three structures to the Grad reformulation
of the Boltzmann equation (to the Grad hierarchy). First, we recognize the
structures in the infinite Grad hierarchy and then in several examples of finite
hierarchies representing extended hydrodynamic equations. In the context of
Grad's hierarchies, we also investigate relations between Hamiltonian and Godunov
structures.
PMID- 28415359
TI - Experimental investigation of the effect of thresholding on temporal statistics
of avalanches.
AB - Avalanchelike behavior reflected in power-law statistics is a ubiquitous property
of extended systems addressed in a number of generic models. The paper presents
an experimental investigation of the effect of thresholding on the statistics of
durations and waiting times between avalanches using acoustic emission
accompanying unstable plastic deformation. It is found that durations of acoustic
events obey power-law statistical distributions robust against thresholding. The
quiescent time distributions follow the Poisson law for low threshold values.
Both these results corroborate the hypothesis that plastic deformation is akin to
the phenomena associated with self-organized criticality (SOC), often advanced on
the basis of power-law amplitude statistics. Increasing the threshold height
enforces deviation from the Poisson distributions toward apparent power-law
behavior. Such a thresholding effect may hinder the experimental determination of
SOC-like dynamics because of the inevitable noise.
PMID- 28415360
TI - Mapping current fluctuations of stochastic pumps to nonequilibrium steady states.
AB - We show that current fluctuations in a stochastic pump can be robustly mapped to
fluctuations in a corresponding time-independent nonequilibrium steady state. We
thus refine a recently proposed mapping so that it ensures equivalence of not
only the averages, but also optimal representation of fluctuations in currents
and density. Our mapping leads to a natural decomposition of the entropy
production in stochastic pumps similar to the "housekeeping" heat. As a
consequence of the decomposition of entropy production, the current fluctuations
in weakly perturbed stochastic pumps are shown to satisfy a universal bound
determined by the steady state entropy production.
PMID- 28415361
TI - Fundamental structural characteristics of planar granular assemblies: Self
organization and scaling away friction and initial state.
AB - The microstructural organization of a granular system is the most important
determinant of its macroscopic behavior. Here we identify the fundamental factors
that determine the statistics of such microstructures, using numerical
experiments to gain a general understanding. The experiments consist of preparing
and compacting isotropically two-dimensional granular assemblies of polydisperse
frictional disks and analyzing the emergent statistical properties of quadrons
the basic structural elements of granular solids. The focus on quadrons is
because the statistics of their volumes have been found to display intriguing
universal-like features [T. Matsushima and R. Blumenfeld, Phys. Rev. Lett. 112,
098003 (2014)PRLTAO0031-900710.1103/PhysRevLett.112.098003]. The dependence of
the structures and of the packing fraction on the intergranular friction and the
initial state is analyzed, and a number of significant results are found. (i) An
analytical formula is derived for the mean quadron volume in terms of three
macroscopic quantities: the mean coordination number, the packing fraction, and
the rattlers fraction. (ii) We derive a unique, initial-state-independent
relation between the mean coordination number and the rattler-free packing
fraction. The relation is supported numerically for a range of different systems.
(iii) We collapse the quadron volume distributions from all systems onto one
curve, and we verify that they all have an exponential tail. (iv) The nature of
the quadron volume distribution is investigated by decomposition into conditional
distributions of volumes given the cell order, and we find that each of these
also collapses onto a single curve. (v) We find that the mean quadron volume
decreases with increasing intergranular friction coefficients, an effect that is
prominent in high-order cells. We argue that this phenomenon is due to an
increased probability of stable irregularly shaped cells, and we test this using
a herewith developed free cell analytical model. We conclude that, in principle,
the microstructural characteristics are governed mainly by the packing procedure,
while the effects of intergranular friction and initial states are details that
can be scaled away. However, mechanical stability constraints suppress slightly
the occurrence of small quadron volumes in cells of order >=6, and the magnitude
of this effect does depend on friction. We quantify in detail this dependence and
the deviation it causes from an exact collapse for these cells. (vi) We argue
that our results support strongly the view that ensemble granular statistical
mechanics does not satisfy the uniform measure assumption of conventional
statistical mechanics. Results (i)-(iv) have been reported in the aforementioned
reference, and they are reviewed and elaborated on here.
PMID- 28415362
TI - Subphase transitions in first-order aggregation processes.
AB - In this paper, we investigate the properties of aggregation transitions in the
context of generic coarse-grained homopolymer systems. By means of parallel
replica-exchange Monte Carlo methods, we perform extensive simulations of systems
consisting of up to 20 individual oligomer chains with five monomers each. Using
the tools of the versatile microcanonical inflection-point analysis, we show that
the aggregation transition is a first-order process consisting of a sequence of
subtransitions between intermediate structural phases. We unravel the properties
of these intermediate phases by collecting and analyzing their individual
contributions towards the density of states of the system. The central theme of
this systematic study revolves around translational entropy and its role in the
striking phenomena of missing intermediate phases. We conclude with a brief
discussion of the scaling properties of the transition temperature and the latent
heat.
PMID- 28415363
TI - Phase-field model of oxidation: Equilibrium.
AB - A phase-field model of an oxide relevant to corrosion resistant alloys for film
thicknesses below the Debye length L_{D}, where charge neutrality in the oxide
does not occur, is formulated. The phase-field model is validated in the Wagner
limit using a sharp interface Gouy-Chapman model for the electrostatic double
layer. The phase-field simulations show that equilibrium oxide films below the
Wagner limit are charged throughout due to their inability to electrostatically
screen charge over the length of the film, L. The character of the defect and
charge distribution profiles in the oxide vary depending on whether reduced
oxygen adatoms are present on the gas-oxide interface. The Fermi level in the
oxide increases for thinner films, approaching the Fermi level of the metal in
the limit L/L_{D}->0, which increases the driving force for adsorbed oxygen
reduction at the gas-oxide interface.
PMID- 28415364
TI - Interfacial adsorption in two-dimensional pure and random-bond Potts models.
AB - We use Monte Carlo simulations to study the finite-size scaling behavior of the
interfacial adsorption of the two-dimensional square-lattice q-states Potts
model. We consider the pure and random-bond versions of the Potts model for
q=3,4,5,8, and 10, thus probing the interfacial properties at the originally
continuous, weak, and strong first-order phase transitions. For the pure systems
our results support the early scaling predictions for the size dependence of the
interfacial adsorption at both first- and second-order phase transitions. For the
disordered systems, the interfacial adsorption at the (disordered induced)
continuous transitions is discussed, applying standard scaling arguments and
invoking findings for bulk critical properties. The self-averaging properties of
the interfacial adsorption are also analyzed by studying the infinite limit-size
extrapolation of properly defined signal-to-noise ratios.
PMID- 28415365
TI - Analyses of kinetic glass transition in short-range attractive colloids based on
time-convolutionless mode-coupling theory.
AB - For short-range attractive colloids, the phase diagram of the kinetic glass
transition is studied by time-convolutionless mode-coupling theory (TMCT). Using
numerical calculations, TMCT is shown to recover all the remarkable features
predicted by the mode-coupling theory for attractive colloids: the glass-liquid
glass reentrant, the glass-glass transition, and the higher-order singularities.
It is also demonstrated through the comparisons with the results of molecular
dynamics for the binary attractive colloids that TMCT improves the critical
values of the volume fraction. In addition, a schematic model of three control
parameters is investigated analytically. It is thus confirmed that TMCT can
describe the glass-glass transition and higher-order singularities even in such a
schematic model.
PMID- 28415366
TI - Statistical mechanics of the triple contact line.
AB - We outline a statistical mechanics of the triple gas-solid-liquid contact line on
a rough plane. The analysis regards the neighborhood of the line as a solid
dotted with cavities. It adopts the simplest mean-field statistical mechanics, in
which each cavity is either full or empty, while being connected to near
neighbors by thin necks. The theory predicts equilibrium angles for advance and
recession in terms of the Young contact angle and the joint statistical
distribution of two quantifiable geometrical parameters representing specific
neck cross-section and specific cavity opening. It attributes contact angle
hysteresis to first-order phase transitions among adjacent cavities, as they
collectively imbibe or reject liquid. It also calculates the potential energy
barriers that hysteresis erects against overcoming contact line pinning. By
determining whether the phase transitions can release latent energy, this ab
initio analysis distinguishes six regimes, including two metastable recession
states. We compare predictions with data for superhydrophobia on microscopic
rods; for hysteresis in the "Wenzel state"; and for variations of the advancing
contact angle with surface energies of the liquid.
PMID- 28415367
TI - Collective phase reduction of globally coupled noisy dynamical elements.
AB - We formulate a theory for the collective phase reduction of globally coupled
noisy dynamical elements exhibiting macroscopic rhythms. We first transform the
Langevin-type equation that represents a group of globally coupled noisy
dynamical elements into the corresponding nonlinear Fokker-Planck equation and
then develop the phase reduction method for limit-cycle solutions to the
nonlinear Fokker-Planck equation. The theory enables us to describe the
collective dynamics of a group of globally coupled noisy dynamical elements by a
single degree of freedom called the collective phase. As long as the group
collectively exhibits macroscopic rhythms, the theory is applicable even when the
coupling and noise are strong; it is also independent of the assumption that each
element of the group is a self-sustained oscillator. We also provide a simple and
accurate numerical algorithm for the collective phase description method and
numerically illustrate the theory using a group of globally coupled noisy
FitzHugh-Nagumo elements.
PMID- 28415368
TI - Role of thermal disequilibrium on natural convection in porous media: Insights
from pore-scale study.
AB - The present study investigates the role of thermal nonequilibrium on natural
convection in a fluid-saturated porous medium heated from below. We conduct high
resolution direct numerical simulation at the pore scale in a two-dimensional
regular porous structure by means of the thermal lattice-Boltzmann method (LBM).
We perform a combination of linear stability analysis of continuum-scale heat
transfer models, and pore-scale and continuum-scale simulations to study the role
of thermal conductivity contrasts among phases on natural convection. The
comparison of pore-scale lattice-Boltzmann simulations with linear stability
analysis reveals that traditional continuum-scale models fail to capture the
correct onset of convection, convection mode, and heat transfer when the thermal
conductivity of the solid obstacles does not match that of the fluid.
PMID- 28415369
TI - From solitons to rogue waves in nonlinear left-handed metamaterials.
AB - In the present work, we explore soliton and roguelike wave solutions in the
transmission line analog of a nonlinear left-handed metamaterial. The
nonlinearity is expressed through a voltage-dependent, symmetric capacitance
motivated by recently developed ferroelectric barium strontium titanate thin-film
capacitor designs. We develop both the corresponding nonlinear dynamical lattice
and its reduction via a multiple scales expansion to a nonlinear Schrodinger
(NLS) model for the envelope of a given carrier wave. The reduced model can
feature either a focusing or a defocusing nonlinearity depending on the frequency
(wave number) of the carrier. We then consider the robustness of different types
of solitary waves of the reduced model within the original nonlinear left-handed
medium. We find that both bright and dark solitons persist in a suitable
parametric regime, where the reduction to the NLS model is valid. Additionally,
for suitable initial conditions, we observe a rogue wave type of behavior that
differs significantly from the classic Peregrine rogue wave evolution, including
most notably the breakup of a single Peregrine-like pattern into solutions with
multiple wave peaks. Finally, we touch upon the behavior of generalized members
of the family of the Peregrine solitons, namely, Akhmediev breathers and
Kuznetsov-Ma solitons, and explore how these evolve in the left-handed
transmission line.
PMID- 28415370
TI - Bubblelike structures generated by activation of internal shape modes in two
dimensional sine-Gordon line solitons.
AB - Nonlinear waves that collide with localized defects exhibit complex behavior.
Apart from reflection, transmission, and annihilation of an incident wave, a
local inhomogeneity can activate internal modes of solitons, producing many
impressive phenomena. In this work we investigate a two-dimensional sine-Gordon
model perturbed by a family of localized forces. We observed the formation of
bubblelike and droplike structures due to local internal shape mode
instabilities. We describe the formation of such structures on the basis of a one
dimensional theory of activation of internal modes of sine-Gordon solitons. An
interpretation of the observed phenomena, in the context of phase transition
theory, is given. Implications in Josephson junctions with a current dipole
device are discussed.
PMID- 28415371
TI - Simple bounds on fluctuations and uncertainty relations for first-passage times
of counting observables.
AB - Recent large deviation results have provided general lower bounds for the
fluctuations of time-integrated currents in the steady state of stochastic
systems. A corollary are so-called thermodynamic uncertainty relations connecting
precision of estimation to average dissipation. Here we consider this problem but
for counting observables, i.e., trajectory observables which, in contrast to
currents, are non-negative and nondecreasing in time (and possibly symmetric
under time reversal). In the steady state, their fluctuations to all orders are
bound from below by a Conway-Maxwell-Poisson distribution dependent only on the
averages of the observable and of the dynamical activity. We show how to obtain
the corresponding bounds for first-passage times (times when a certain value of
the counting variable is first reached) and their uncertainty relations. Just
like entropy production does for currents, dynamical activity controls the bounds
on fluctuations of counting observables.
PMID- 28415372
TI - Ultrametricity of optimal transport substates for multiple interacting paths over
a square lattice network.
AB - We model a set of point-to-point transports on a network as a system of
polydisperse interacting self-avoiding walks (SAWs) over a finite square lattice.
The ends of each SAW may be located both at random, uniformly distributed,
positions or with one end fixed at a lattice corner. The total energy of the
system is computed as the sum over all SAWs, which may represent either the time
needed to complete the transport over the network, or the resources needed to
build the networking infrastructure. We focus especially on the second aspect by
assigning a concave cost function to each site to encourage path overlap. A
simulated annealing optimization, based on a modified Berg-Foerster-Aragao de
Carvalho-Caracciolo-Froehlich (BFACF) algorithm developed for polymers, is used
to probe the complex conformational substate structure at zero temperature. We
characterize the average cost gains (and path-length variations) for increasing
polymer density with respect to a Dijkstra routing and find a nonmonotonic
behavior as recently found for random networks. We observe the emergence of
ergodicity breaking and of nontrivial overlap distributions among replicas when
switching from a convex to a concave cost function (e.g., x^{gamma}, where x
represents the node overlap). Finally, we show that the space of ground states
for gamma<1 is compatible with an ultrametric structure, as seen in many complex
systems such as some spin glasses.
PMID- 28415373
TI - How turbulence fronts induce plasma spin-up.
AB - A calculation which describes the spin-up of toroidal plasmas by the radial
propagation of turbulence fronts with broken parallel symmetry is presented. The
associated flux of parallel momentum is calculated by using a two-scale direct
interaction approximation in the weak turbulence limit. We show that fluctuation
momentum spreads faster than mean flow momentum. Specifically, the turbulent flux
of wave momentum is stronger than the momentum pinch. The scattering of
fluctuation momentum can induce edge-core coupling of toroidal flows, as observed
in experiments.
PMID- 28415374
TI - Explicit calculation of nuclear-magnetic-resonance relaxation rates in small
pores to elucidate molecular-scale fluid dynamics.
AB - Nuclear-magnetic-resonance (NMR) spin-lattice (T_{1}^{-1}) and spin-spin (T_{2}^{
1}) relaxation rate measurements can act as effective nondestructive probes of
the nanoscale dynamics of ^{1}H spins in porous media. In particular, fast-field
cycling T_{1}^{-1} dispersion measurements contain information on the dynamics of
diffusing spins over time scales spanning many orders of magnitude. Previously
published experimental T_{1}^{-1} dispersions from a plaster paste, synthetic
saponite, mortar, and oil-bearing shale are reanalyzed using a model and
associated theory which describe the relaxation rate contributions due to the
interaction between spin ensembles in quasi-two-dimensional pores. Application of
the model yields physically meaningful diffusion correlation times for all
systems. In particular, the surface diffusion correlation time and the surface
desorption time take similar values for each system, suggesting that surface
mobility and desorption are linked processes. The bulk fluid diffusion
correlation time is found to be two to five times the value for the pure liquid
at room temperature for each system. Reanalysis of the oil-bearing shale yields
diffusion time constants for both the oil and water constituents. The shale is
found to be oil wetting and the water T_{1}^{-1} dispersion is found to be
associated with aqueous Mn^{2+} paramagnetic impurities in the bulk water. These
results escalate the NMR T_{1}^{-1} dispersion measurement technique as the
primary probe of molecular-scale dynamics in porous media yielding diffusion
parameters and a wealth of information on pore morphology.
PMID- 28415375
TI - Nonlinear Monte Carlo model of superdiffusive shock acceleration with magnetic
field amplification.
AB - Fast collisionless shocks in cosmic plasmas convert their kinetic energy flow
into the hot downstream thermal plasma with a substantial fraction of energy
going into a broad spectrum of superthermal charged particles and magnetic
fluctuations. The superthermal particles can penetrate into the shock upstream
region producing an extended shock precursor. The cold upstream plasma flow is
decelerated by the force provided by the superthermal particle pressure gradient.
In high Mach number collisionless shocks, efficient particle acceleration is
likely coupled with turbulent magnetic field amplification (MFA) generated by the
anisotropic distribution of accelerated particles. This anisotropy is determined
by fast particle transport, making the problem strongly nonlinear and multiscale.
Here, we present a nonlinear Monte Carlo model of collisionless shock structure
with superdiffusive propagation of high-energy Fermi accelerated particles
coupled to particle acceleration and MFA, which affords a consistent description
of strong shocks. A distinctive feature of the Monte Carlo technique is that it
includes the full angular anisotropy of the particle distribution at all
precursor positions. The model reveals that the superdiffusive transport of
energetic particles (i.e., Levy-walk propagation) generates a strong quadruple
anisotropy in the precursor particle distribution. The resultant pressure
anisotropy of the high-energy particles produces a nonresonant mirror-type
instability that amplifies compressible wave modes with wavelengths longer than
the gyroradii of the highest-energy protons produced by the shock.
PMID- 28415376
TI - Streamwise localization of traveling wave solutions in channel flow.
AB - Channel flow of an incompressible fluid at Reynolds numbers above 2400 possesses
a number of different spatially localized solutions that approach laminar flow
far upstream and downstream. We use one such relative time-periodic solution,
which corresponds to a spatially localized version of a Tollmien-Schlichting
wave, to illustrate how the upstream and downstream asymptotics can be computed
analytically. In particular, we show that for these spanwise uniform states the
asymptotics predict the exponential localization that has been observed for
numerically computed solutions of several canonical shear flows but never
properly understood theoretically.
PMID- 28415377
TI - Delay-induced depinning of localized structures in a spatially inhomogeneous
Swift-Hohenberg model.
AB - We report on the dynamics of localized structures in an inhomogeneous Swift
Hohenberg model describing pattern formation in the transverse plane of an
optical cavity. This real order parameter equation is valid close to the second
order critical point associated with bistability. The optical cavity is
illuminated by an inhomogeneous spatial Gaussian pumping beam and subjected to
time-delayed feedback. The Gaussian injection beam breaks the translational
symmetry of the system by exerting an attracting force on the localized
structure. We show that the localized structure can be pinned to the center of
the inhomogeneity, suppressing the delay-induced drift bifurcation that has been
reported in the particular case where the injection is homogeneous, assuming a
continuous wave operation. Under an inhomogeneous spatial pumping beam, we
perform the stability analysis of localized solutions to identify different
instability regimes induced by time-delayed feedback. In particular, we predict
the formation of two-arm spirals, as well as oscillating and depinning dynamics
caused by the interplay of an attracting inhomogeneity and destabilizing time
delayed feedback. The transition from oscillating to depinning solutions is
investigated by means of numerical continuation techniques. Analytically, we use
an order parameter approach to derive a normal form of the delay-induced Hopf
bifurcation leading to an oscillating solution. Additionally we model the
interplay of an attracting inhomogeneity and destabilizing time delay by
describing the localized solution as an overdamped particle in a potential well
generated by the inhomogeneity. In this case, the time-delayed feedback acts as a
driving force. Comparing results from the later approach with the full Swift
Hohenberg model, we show that the approach not only provides an instructive
description of the depinning dynamics, but also is numerically accurate
throughout most of the parameter regime.
PMID- 28415378
TI - Drag law for an intruder in granular sediments.
AB - We investigate the drag experienced by a spherical intruder moving through a
medium consisting of granular hydrogels immersed in water as a function of its
depth, size, and speed. The medium is observed to display a yield stress with a
finite force required to move the intruder in the quasistatic regime at low
speeds before rapidly increasing at high speeds. In order to understand the
relevant time scales that determine drag, we estimate the inertial number I given
by the ratio of the time scales required to rearrange grains due to the
overburden pressure and imposed shear and the viscous number J given by the ratio
of the time scales required to sediment grains in the interstitial fluid and
imposed shear. We find that the effective friction MU_{e} encountered by the
intruder can be parametrized by I=sqrt[rho_{g}/P_{p}]v_{i}, where rho_{g} is the
density of the granular hydrogels, v_{i} is the intruder speed, and P_{p} is the
overburden pressure due to the weight of the medium, over a wide range of I where
the Stokes number St=I^{2}/J?1. We then show that MU_{e} can be described by the
function MU_{e}(I)=MU_{0}+alphaI^{beta}, where MU_{0}, alpha, and beta are
constants that depend on the medium. This formula can be used to predict the drag
experienced by an intruder of a different size at a different depth in the same
medium as a function of its speed.
PMID- 28415379
TI - Chimeras and clusters in networks of hyperbolic chaotic oscillators.
AB - We show that chimera states, where differentiated subsets of synchronized and
desynchronized dynamical elements coexist, can emerge in networks of hyperbolic
chaotic oscillators subject to global interactions. As local dynamics we employ
Lozi maps, which possess hyperbolic chaotic attractors. We consider a globally
coupled system of these maps and use two statistical quantities to describe its
collective behavior: the average fraction of elements belonging to clusters and
the average standard deviation of state variables. Chimera states, clusters,
complete synchronization, and incoherence are thus characterized on the space of
parameters of the system. We find that chimera states are related to the
formation of clusters in the system. In addition, we show that chimera states
arise for a sufficiently long range of interactions in nonlocally coupled
networks of these maps. Our results reveal that, under some circumstances,
hyperbolicity does not impede the formation of chimera states in networks of
coupled chaotic systems, as it had been previously hypothesized.
PMID- 28415380
TI - miR-98 inhibits expression of TWIST to prevent progression of non-small cell lung
cancers.
AB - Evidence is mounting that micro RNAs (miRNAs) play a critical role in tumor
development. However, the role of miRNAs in lung cancer progression remains
largely unknown. Herein, we found that miR-98 significantly impaired in patients
with non-small cell lung cancers (NSCLC) and was a novel regulator of NSCLC
progression. Patients with high miR-98 expression had a longer overall survival
than with low miR-98 expression (p=0.0495). miR-98 expression level inversely
correlated with TWIST mRNA level in 71 clinical tissue specimens of NSCLC
(p<0.01). Luciferase assay demonstrated that miR-98 interacted binding sites in
the TWIST 3'-UTR and reduced expression of TWIST, resulting in repression of cell
migration and invasion via impeding TWIST-mediated EMT. Furthermore, introduction
of synthetic miR-98 caused growth arrest by inactivating TWIST-Akt-CDK4/CDK6.
Meanwhile, miR-98 mimic induced apoptosis by targeting TWIST-Akt axis. In a
conclusion, these observations imply that miR-98 may act as a tumor suppressor in
NSCLC to decelerate NSCLC aggressiveness by inhibiting TWIST expression.
PMID- 28415381
TI - Biocompatibility study on Ni-free Ti-based and Zr-based bulk metallic glasses.
AB - Safety and reliability are crucial issues for medical instruments and implants.
In the past few decays, bulk metallic glasses (BMGs) have drawn attentions due to
their superior mechanical properties, good corrosion resistance, antibacterial
and good biocompatibility. However, most Zr-based and Ti-based BMGs contain Ni as
an important element which is prone to human allergy problem. In this study, the
Ni-free Ti-based and Zr-based BMGs, Ti40Zr10Cu36Pd14, and Zr48Cu36Al8Ag8, were
selected for systematical evaluation of their biocompatibility. Several
biocompatibility tests, co-cultural with L929 murine fibroblast cell line, were
carried out on these two BMGs, as well as the comparison samples of Ti6Al4V and
pure Cu. The results in terms of cellular adhesion, cytotoxicity, and metallic
ion release affection reveal that the Ti40Zr10Cu36Pd14 BMG and Ti6Al4V exhibit
the optimum biocompatibility; cells still being attached on the petri dish with
good adhesion and exhibiting the spindle shape after direct contact test.
Furthermore, the Ti40Zr10Cu36Pd14 BMG showed very low Cu ion release level, in
agreement with the MTT results. Based on the current findings, it is believed
that Ni-free Ti-based BMG can act as an ideal candidate for medical implant.
PMID- 28415382
TI - Alkali-etching growth of nest-like Ag@mTiO2 hierarchical nanostructures and their
potential applications.
AB - Porous nanomaterials have attracted extensive interests in adsorption, catalysis,
biosensors, and biomedicine due to their high surface area, well-defined pore
structure and tunable pore size. However, how to obtain porous nanomaterials of
desirable component and unique structure with multifunctionalities and synergetic
properties is still a great challenge. In this work, a novel nest-like Ag@mTiO2
hierarchical nanostructure with Ag nanoparticle as the core and a mesoporous
crystalline TiO2 as the protective shell was successfully prepared by layer-by
layer assembly technique and alkali-etching hydrothermal route. By simply
changing the conditions of alkali etching, different nanostructures could be
obtained, such as core-shell or rattle type. In the process, the thickness of
coating silica layer and TiO2 shell both played important roles for the formation
of desired nanostructures. The as-prepared products had a large specific surface
area of 301m2/g and a tailored TiO2 outer shell. Raman spectra results showed
perfect SERS signal of the tags enhanced and remained good stability even after
one month. Doxycycline (Doxy) was chosen to evaluate their drug loading and
controlled release properties. The results indicated that the obtained Ag@mTiO2
nanoparticles exhibited good biocompatibility and excellent drug-loading
capacity. Consequently, they are also expected to serve as ideal candidates for
more potential applications including photocatalysis, drug controlled release,
biosensor and cell imaging, etc.
PMID- 28415383
TI - Preparation and characterization of a novel degradable nano
hydroxyapatite/poly(lactic-co-glycolic) composite reinforced with bamboo fiber.
AB - It is a promising and challenging to achieve an ideal poly (lactic-co-glycolic)
(PLGA)-based composite. In this paper, bamboo fiber (BF) was firstly designed to
incorporate into nano-hydroxyapatite/PLGA (n-HA/PLGA) composite, and a series of
novel biodegradable BF/n-HA/PLGA ternary composites with different BF amounts
(0wt%, 5wt%, 10wt% and 20wt%) were prepared by solution mixing method. The effect
of BF content on the crystallization behavior, interface structure and mechanical
property of BF/n-HA/PLGA ternary composite was investigated by X-ray diffraction
pattern (XRD), differential scanning calorimeter (DSC) and scanning electron
microscope (SEM), comparing with pure PLGA and n-HA/PLGA composite. The results
showed that BF further promoted the crystallization of PLGA acting as a
heterogeneous nucleation agent, and the addition of 10wt% BF was the best benefit
to promote the crystallization. However, the higher addition content of BF caused
more agglomeration in n-HA/PLGA matrix, which decreased gradually the mechanical
properties of the BF/n-HA/PLGA composite. In conclusion, the addition content of
5wt% BF to n-HA/PLGA matrix was an appropriate proportion, which can achieved the
best mechanical reinforce effectiveness, suggesting that BF/n-HA/PLGA composite
had more potential in biomedical application than n-HA/PLGA composite.
PMID- 28415384
TI - Preparation and characterization of expanded graphite/metal oxides for
antimicrobial application.
AB - Composite materials based on expanded graphite (EG) and metal oxide (MO)
particles was prepared by an explosive combustion and blending method. The
objective of the study was to develop EG impregnated with metal oxide
particulates (Ag2O, CuO and ZnO) and evaluate the level of protection the
materials conferred against biological agents. The physical properties of the
EG/MO composites were examined using SEM, EDX and XRD spectroscopy, and the
results indicated that the MO particles were incorporated into the EG matrix
after impregnation. The antimicrobial activities of the EG/MO composites against
Gram-positive bacteria, Gram-negative bacteria and Bacillus anthracis were
investigated using zone of inhibition, minimum inhibitory concentration (MIC),
minimum bactericidal concentration (MBC) and plate-counting methods. EG/Ag2O
exhibited a stronger antibacterial activity than EG/CuO and EG/ZnO, with a MIC of
0.3mg/mL and a MBC of 0.5mg/mL. To the best of our knowledge, few studies have
demonstrated that EG/MO composites can inhibit the growth of Bacillus anthracis
adhered cells, thus preventing the process of biofilm formation. Nanoscale metal
oxides display enhanced reactive properties toward bacteria due to their high
surface area, large number of highly reactive edges, corner defect sites and high
surface to volume ratio.
PMID- 28415385
TI - Antitubercular activity of ZnO nanoparticles prepared by solution combustion
synthesis using lemon juice as bio-fuel.
AB - In this study, we report the synthesis, structural and morphological
characteristics of zinc oxide (ZnO) nanoparticles using solution combustion
synthesis method where lemon juice was used as the fuel. In vitro anti-tubercular
activity of the synthesized ZnO nanoparticles and their biocompatibility studies,
both in vitro and in vivo were carried out. The synthesized nanoparticles showed
inhibition of Mycobacterium tuberculosis H37Ra strain at concentrations as low as
12.5MUg/mL. In vitro cytotoxicity study performed with normal mammalian cells
(L929, 3T3-L1) showed that ZnO nanoparticles are non-toxic with a Selectivity
Index (SI) >10. Cytotoxicity performed on two human cancer cell lines DU-145 and
Calu-6 indicated the anti-cancer activity of ZnO nanoparticles at varied
concentrations. Results of blood hemolysis indicated the biocompatibility of ZnO
nanoparticles. Furthermore, in vivo toxicity studies of ZnO nanoparticles
conducted on Swiss albino mice (for 14days as per the OECD 423 guidelines) showed
no evident toxicity.
PMID- 28415386
TI - Modification and evaluation of micro-nano structured porous bacterial cellulose
scaffold for bone tissue engineering.
PMID- 28415387
TI - Dextrose modified flexible tasar and muga fibroin films for wound healing
applications.
AB - This paper is focused on preparation and characterization of regenerated muga and
tasar fibroin flexible films from cocoon using ionic liquid. These flexible muga
and tasar fibroin films were prepared by incorporating dextrose (5 to 15% w/w) as
plasticizer. The mechanical, thermal, physical, morphological and biological
properties of dextrose plasticized muga and tasar fibroin films were
characterized. These plasticized films showed higher elongation at break as well
as water holding capacity as compared to the un-plasticized films. The surface
roughness and water absorbance capacity of the dextrose plasticized films were
higher than un-plasticized films, which results in improved adherence and
proliferation of L929 fibroblast cells. Gentamicin loaded plasticized muga and
tasar fibroin films showed slightly higher rate of release as compared to un
plasticized films. The biodegradability of dextrose plasticized films was
significantly higher as compared to their respective counterpart. The
regeneration of flexible muga and tasar silk fibroin films pave the way to expand
potential use of non-mulberry in the field of biomedical such as wound dressing.
PMID- 28415388
TI - Targeted delivery of docetaxel via Pi-Pi stacking stabilized dendritic polymeric
micelles for enhanced therapy of liver cancer.
AB - Delivery of taxane-based chemotherapeutics including Docetaxel (DTX) by
conventional polymeric micelles still suffers from insufficient stability and
rapid premature release during the circulation, which limits their targeting and
anticancer efficiency. To conquer these challenges, we developed a novel DTX
loaded Pi-Pi stacking-stabilized dendritic polymeric micelle for targeted therapy
of liver cancer. This dendritic polymeric micelle, referred to DPM-DTX-cRGD, was
self-assembled from DTX and biodegradable dendritic block copolymers
Poly(amidoamine)-poly(gamma-benzyl-l-Glutamate)-b-polyethylene glycol-cRGD (PAM
PBLG-b-PEG-cRGD). DPM-DTX-cRGD held robust stability due to its covalent
dendritic structure and would load abundant DTX with excellent retention via Pi
Pi stacking between DTX and the aromatic groups of the PBLG segments. The
cellular uptake studies demonstrated that the cRGD-conjugated dendritic polymeric
micelle (DPM) exhibited much higher cellular uptake in human liver cancer HepG2
cells than non-targeted DPM. The MTT assay also confirmed that DPM-DTX-cRGD
caused much greater cytotoxicity than non-targeted DPM-DTX and a clinically
available DTX formulation (Taxotere(r)). Therefore, this DPM-DTX-cRGD provides a
novel attractive approach for targeted therapy of liver cancer.
PMID- 28415389
TI - Antibacterial, osteogenic, and angiogenic activities of SrTiO3 nanotubes embedded
with Ag2O nanoparticles.
AB - Biomedical titanium (Ti) implants with good anti-infective, osteogenic, and
angiogenic properties are in great demand. SrTiO3 nanotubes (NTs) are embedded
with silver oxide (Ag2O) nanoparticles (NPs) (denoted as NT-Sr-Ag) by a
hydrothermal treatment of TiO2 NTs containing Ag2O NPs (denoted as NT-Ag) in a
Sr(OH)2 solution. The morphology, composition, microstructure, ion release
phenomenon, as well as antibacterial, osteogenic, and angiogenic activities are
investigated in details. During the hydrothermal treatment, the amorphous TiO2 in
the NTs morphs into cubic SrTiO3 gradually and the ordered nanotubular
architecture is preserved. Some Ag2O NPs are incorporated into the structure
although some of them dissolve in the solution. Long-term bacterial resistance
against Staphylococcus aureus is observed as a result of the prolonged and
controllable Ag+ release. NT-Sr-Ag can also release Sr2+ similarly to stimulate
osteoblasts to secrete the vascular endothelial growth factor (VEGF). Both the
released Sr2+ and secreted VEGF upregulate the alkaline phosphatase (ALP)
activity and extracellular matrix mineralization of osteoblasts. Furthermore,
better angiogenic activity is observed when endothelial cells are cultured in NT
Sr-Ag conditioned media when compared with that in NT-Ag conditioned media, which
is believed to be ascribed to the positive regulation of VEGF secretion of Sr2+.
NT-2Sr-Ag and NT-3Sr-Ag (Hydrothermal treatment for 2 and 3h, respectively)
exhibit excellent antibacterial, osteogenic, and angiogenic activities and are
promising in biomedical implants.
PMID- 28415390
TI - Synthesis, spectroscopic and DNA binding ability of CoII, NiII, CuII and ZnII
complexes of Schiff base ligand (E)-1-(((1H-benzo[d]imidazol-2
yl)methylimino)methyl)naphthalen-2-ol. X-ray crystal structure determination of
cobalt (II) complex.
AB - A novel Schiff base ligand, (E)-1-(((1H-benzo[d]imidazol-2
yl)methylimino)methyl)naphthalen-2-ol (HL), has been designed and synthesized in
addition to its metal chelates [Co(L)2].l2H2O, [Ni(L)Cl.(H2O)2].5H2O, [Cu(L)Cl]
and [Zn(L)(CH3COO)]. The structures of the isolated compounds have been confirmed
and identified by means of different spectral and physicochemical techniques
including CHN analysis, 1H &13C NMR, mass spectral analysis, molar conductivity
measurement, UV-Vis, infrared, magnetic moment in addition to TGA technique. The
infrared spectral results ascertained that the ligand acts as monobasic
tridentate binding to the metal centers via deprotonated hydroxyl oxygen,
azomethine and imidazole nitrogen atoms. The UV-Vis, magnetic susceptibility and
molar conductivity data implied octahedral geometry for Co(II) & Ni(II)
complexes, tetrahedral for Zn(II) complex and square planar for Cu(II) complex. X
ray structural analysis of Co(II) complex 1 has been reported and discussed.
Moreover, the type of interaction between the ligand & its complexes towards
salmon sperm DNA (SS-DNA) has been examined by the measurement of absorption
spectra and viscosity which confirmed that the ligand and its complexes interact
with DNA via intercalation interaction as concluded from the values of binding
constants (Kb).
PMID- 28415391
TI - Biological activity evaluation of magnesium fluoride coated Mg-Zn-Zr alloy in
vivo.
AB - AIM: To explore the biodegradable characteristics and biological properties,
which could promote new bone formation, of MgF2 coated magnesium alloy (Mg-3wt%Zn
0.5wt%Zr) in rabbits. METHODS: Magnesium alloy with MgF2 coating was made and the
MgF2/Mg-Zn-Zr was implanted in the femoral condyle of rabbits. Twelve healthy
adult Japanese white rabbits in weight of 2.8-3.2kg were averagely divided into
A(Mg-Zn-Zr) group and B(MgF2/MgZn-Zr) group. Indexes such as microstructural
evolution, SEM scan, X-ray, Micro-CT and mechanical properties were observed and
detected at 1th day, 2th, 4th, 8th, 12th, 24th week after implantation. RESULTS:
Low-density regions occurred around the cancellous bone, and the regions
gradually expanded during the 12weeks after implantation. The implant was
gradually absorbed from 12 to 24weeks. The density of surrounding cancellous bone
increased compared with the 12th week data. The degradation rate of B group was
lower than that of A group (P<0.01), while the density of the surrounding
cancellous bone increased more evenly. In B group, SEM images after 12weeks
showed the rich bone tissues on the alloy surface that were attached by active
fibers. Micro-CT also presented alloy residue potholes on the surfaces of alloy
combinated with bone tissues. Additionally, the trabecular bone had relatively
integrated structures with surrounding cavities. CONCLUSIONS: MgF2 can
effectively decrease the degradation rate of Mg-Zn-Zr in vivo. Mg-Zn-Zr coated
with MgF2 can effectively inhibit the corrosion, and delay the release of
magnesium ions. The biological properties of the coating itself presented good
biocompatibility and bioactivity.
PMID- 28415392
TI - Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for
tissue engineering: Preparation and in vitro evaluation.
AB - Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical
applications, including tissue engineering, due to their biocompatibility, high
water solubility, low protein adsorption, and chemical stability. However, non
charged surface of PVA-based hydrogels is not optimal for cell adhesion and
spreading. Here, cross-linked macroporous hydrogels based on low molecular weight
acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol
groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity,
charged groups were introduced to the hydrogel composition. For this purpose, Acr
PVA was copolymerized with either negatively charged acrylic acid (AA) or
positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A
surface charge of the obtained hydrogels was found to be in function of the co
monomer type and content. Confocal microscopy observations confirmed that
adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal
stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were
better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA
monomer content from 5 to 15mol% resulted in the enhancement of cell viability
which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non
modified Acr-PVA hydrogel sample.
PMID- 28415393
TI - The relationship between particle morphology and rheological properties in
injectable nano-hydroxyapatite bone graft substitutes.
AB - Biomaterials composed of hydroxyapatite (HA) are currently used for the treatment
of bone defects resulting from trauma or surgery. However, hydroxyapatite
supplied in the form of a paste is considered a very convenient medical device
compared to the materials where HA powder and liquid need to be mixed immediately
prior to the bone treatment during surgery. In this study we have tested a series
of hydroxyapatite (HA) pastes with varying microstructure and different
rheological behaviour to evaluate their injectability and biocompatibility. The
particle morphology and chemical composition were evaluated using HRTEM, XRD and
FTIR. Two paste-types were compared, with the HA particles of both types being
rod shaped with a range of sizes between 20 and 80nm while differing in the
particle aspect ratio and the degree of roundness or sharpness. The pastes were
composed of pure HA phase with low crystallinity. The rheological properties were
evaluated and it was determined that the pastes behaved as shear-thinning, non
Newtonian liquids. The difference in viscosity and yield stress between the two
pastes was investigated. Surprisingly, mixing of these pastes at different ratios
did not alter viscosity in a linear manner, providing an opportunity to produce a
specific viscosity by mixing the two materials with different characteristics.
Biocompatibility studies suggested that there was no difference in vitro cell
response to either paste for primary osteoblasts, bone marrow mesenchymal stromal
cells, osteoblast-like cells, and fibroblast-like cells. This class of
nanostructured biomaterial has significant potential for use as an injectable
bone graft substitute where the properties may be tailored for different clinical
indications.
PMID- 28415394
TI - Ultra-sensitive detection of ibuprofen (IBP) by electrochemical aptasensor using
the dendrimer-quantum dot (Den-QD) bioconjugate as an immobilization platform
with special features.
AB - This study describes a high-performance electrochemical aptasensor which is
employed to detect Ibuprofen (IBP) as a painkiller drug by using a novel platform
as an integrated sensing interface. In order to make the aptasensor, the Den-QD
bioconjugate was immobilized on the surface of a GC electrode and followed the
Apt was incubated on this surface. The incubation of the IBP on the aptasensor
surface and the formation of the Apt/IBP complex, led to a hindered electron
transfer reaction on the sensing surface, which decreased the peak current of the
redox probe. Under the optimum condition, the assay had two dynamic ranges with a
detection limit down to 333fM. The developed aptasensor reliably detects IBP in a
real sample. Our results demonstrated that the proposed strategy has many
advantages and the Den-QD bioconjugate may become a promising nanocomposite for
the electrochemical sensing applications.
PMID- 28415395
TI - Drug kinetics release from Eudragit - Tenofovir@SiOC tablets.
AB - A novel drug release system has been obtained in form of tablets from Eudragit(r)
RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active
carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative
purposes. The porous silicon oxycarbide presents a bimodal mesopore size
distribution that is maintained after functionalization with amino groups. We
have studied the adsorption kinetics and adsorption equilibrium when the
materials are loaded with tenofovir and, in all cases, pseudo-second order
kinetics and Langmuir isotherm have been revealed as the most representative
models describing the kinetic and thermodynamic parameters. Besides, the
tenofovir adsorption on these materials turns out to be a favorable process. In
vitro release of tenofovir has been studied in simulated vaginal medium by
applying different release models. Continuous tenofovir release for >20days has
been obtained for the SiOC material functionalized with amine groups. We
concluded that the drug release occurs in two steps that involve a drug diffusion
step through the material pores and diffusion through the swollen polymer. The
interactions between the tenofovir drug and de amine groups of the functionalized
silicon oxycarbide also play an important role in the release process.
PMID- 28415396
TI - Role of silver/zinc oxide in affecting de-adhesion strength of Staphylococcus
aureus on polymer biocomposites.
AB - A single-cell force spectroscopy is utilized to characterize the dynamics of the
transient interaction (0-10s) between alive Staphylococcus aureus and ultra-high
molecular weight polyethylene (UHMWPE). Adhesion force of bacteria upon addition
of antibacterial additives (i.e. silver (Ag) nanoparticles and zinc oxide (ZnO)
micro-rods) has been evaluated. Addition of Ag and ZnO reduces the colony forming
units (CFUs) from 93+/-7 (UHMWPE) to 23+/-5 (U+3wt.% Ag+3wt.% ZnO) on 10*10mm2
area of sample surface. Presence of ZnO causes increase in the surface free
energy from 29.1 (UHMWPE) to 32.3mJ/m2 (UHMWPE+1wt.% ZnO) and 32.3mJ/m2 for
U+3wt.% ZnO whereas due to Ag the surface free energy decreased to 28.3mJ/m2 and
28.4mJ/m2 for UHMWPE+1wt.% Ag and U+3wt.% Ag respectively. At a contact time of
10s bacterial adhesion on U+1wt.% Ag+1wt.% ZnO, U+3wt.% Ag and U+3wt.% Ag+3wt.%
ZnO showed lowest adhesion forces, ~2.6nN, ~2.9nN and ~3.2N respectively as
compared to neat UHMWPE (~4nN) due to a lower surface free energies, but U+1wt.%
Ag and U+1wt.% ZnO and U+3wt.% ZnO show higher adhesion force due their higher
surface free energy. Ag nanoparticles reduce the live bacteria count whereas ZnO
reduces the bacterial retention and combination of both acts synergistically so
the count of live bacteria as well as total bacterial density reduced in U-Ag-ZnO
composite samples.
PMID- 28415397
TI - Surface-modified bioresorbable electrospun scaffolds for improving
hemocompatibility of vascular grafts.
AB - The replacement of small-diameter vessels is one of the main challenges in tissue
engineering. Moreover, the surface modification of small-diameter vascular grafts
(SDVG) is a key factor in the success of the therapy due to their increased
thrombogenicity and infection susceptibility caused by the lack of a functional
endothelium. In this work, electrospun scaffolds were prepared from blends of
poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) with a composition
designed to perform as SDVG inner layer. The scaffolds were then successfully
surface-modified with heparin following two different strategies that rely on
grafting of heparin to either PLLA or PHD functional groups. Both strategies
afforded high heparin density, being higher for urethane methodology. The
functionalized scaffolds did not cause hemolysis and inhibited platelet adhesion
to a large extent. However, lysozyme/heparin-functionalized scaffolds obtained
through urethane methodology achieved the highest platelet attachment inhibition.
The increase in hydrophilicity and water absorption of the surface-functionalized
nanostructures favored adhesion and proliferation of human adipose-derived stem
cells. Heparinized surfaces conjugated with lysozyme presented microbial
hydrolysis activity dependent on heparin content. Overall, a better performance
obtained for urethane-modified scaffold, added to the fact that no chain scission
is involved in urethane methodology, makes the latter the best choice for surface
modification of PLLA/PHD 50/50 electrospun scaffolds. Scaffolds functionalized by
this route may perform as advanced components of SDVG suitable for vascular
tissue engineering, exhibiting biomimetic behavior, avoiding thrombi formation
and providing antimicrobial features.
PMID- 28415398
TI - Combinatorial delivery of superparamagnetic iron oxide nanoparticles (gammaFe2O3)
and doxorubicin using folate conjugated redox sensitive multiblock polymeric
nanocarriers for enhancing the chemotherapeutic efficacy in cancer cells.
AB - Redox sensitive, folate conjugated multiblock polymeric system of (-PLGA-PEG-PLGA
urethane-ss-) demonstrated self-assembly into stable nanoplatforms. The polymeric
nanocarriers were encapsulated with doxorubicin and highly crystalline gammaFe2O3
superparamagnetic iron oxide nanoparticles (SPIONs), for co-delivery of the same
to cancer cells, with average particle size of ~170nm and zeta potential of ~
33mV. Furthermore, the designed formulation was evaluated for protein adsorption,
hemo-cytocompatibility and stability. Glutathione (GSH) induced redox sensitivity
of the nanocarriers was depicted by ~4.47 fold increase in drug release in the
presence of 10mM GSH. In vitro cellular uptake studies of the designed
nanocarriers showed synergistic cytotoxic effect in folate overexpressing cells
(HeLa and MDA-MB-231), after subjecting the cells to radio frequency (RF) induced
hyperthermia (~43 degrees C). Negligible effect of the combinatorial therapy was
observed in normal cells (L929). The developed polymeric system depicted facile
synthesis, reproducibility and potential for achieving combinatorial and targeted
delivery of drug and SPIONs to cancer cells. This combinatorial approach can help
in achieving better therapeutic effect with minimal side effects of chemotherapy.
PMID- 28415399
TI - Novel keratin modified bacterial cellulose nanocomposite production and
characterization for skin tissue engineering.
AB - As it is known that bacterial cellulose (BC) is a biocompatible and natural
biopolymer due to which it has a large set of biomedical applications. But still
it lacks some desired properties, which limits its uses in many other
applications. Therefore, the properties of BC need to be boosted up to an
acceptable level. Here in this study for the first time, a new natural
nanocomposite was produced by the incorporating keratin (isolated from human
hair) to the BC (produced by Acetobacter xylinum) to enhance dermal fibroblast
cells' attachment. Two different approaches were used in BC based nanocomposite
production: in situ and post modifications. BC/keratin nanocomposites were
characterized using SEM, FTIR, EDX, XRD, DSC and XPS analyses. Both production
methods have yielded successful results for production of BC based nanocomposite
containing keratin. In vitro cell culture experiments performed with human skin
keratinocytes and human skin fibroblast cells indicate the potential of the novel
BC/keratin nanocomposites for use in skin tissue engineering.
PMID- 28415400
TI - Antibacterial and cytocompatible nanotextured Ti surface incorporating silver via
single step hydrothermal processing.
AB - Nanosurface modification of Titanium (Ti) implants and prosthesis is proved to
enhance osseointegration at the tissue-implant interface. However, many of these
products lack adequate antibacterial capability, which leads to implant
loosening. As a curative strategy, in this study, nanotextured Ti substrates
embedded with silver nanoparticles were developed through a single step
hydrothermal processing in an alkaline medium containing silver nitrate at
different concentrations (15, 30 and 75MUM). Scanning electron micrographs
revealed a non-periodically oriented nanoleafy structure on Ti (TNL) decorated
with Ag nanoparticles (nanoAg), which was verified by XPS, XRD and EDS analysis.
This TNLAg substrate proved to be mechanically stable upon nanoindentation and
nanoscratch tests. Silver ions at detectable levels were released for a period of
~28days only from substrates incorporating higher nanoAg content. The samples
demonstrated antibacterial activity towards both Escherichia coli and
Staphylococcus aureus, with a more favorable response to the former.
Simultaneously, Ti substrates incorporating nanoAg at all concentrations
supported the viability, proliferation and osteogenic differentiation of
mesenchymal stem cells. Overall, nanoAg incorporation into surface modified Ti
via a simple one-step thermochemical method is a favorable strategy for producing
implants with dual characteristics of antibacterial activity and cell
compatibility.
PMID- 28415401
TI - A new 2-amino-3-pynanopyrane-3- carbonitrile derivative for electrocatalytic
oxidation and determination of hydrazine.
AB - A noble glassy carbon electrode modified with Au nanoparticles and 2-amino-4-(3,4
dihydroxyphenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3
carbonitrile, was fabricated for electrocatalytic determination of hydrazine
(AuNPs/APP/GCE). Large over-potential and interference of some species are two
limitation factors for the determination of hydrazine at bare electrode. This
modified electrode is able to shift a signal to the negative potential, and can
amplify the oxidation current of hydrazine by 28.0 time, compared to bare
electrode. The diffusion coefficient, D, and the heterogeneous rate constant, kh,
for the oxidation of hydrazine at the modified surface were calculated by
chronoamperometric studies. Finally, the fabricated sensor was agreeably utilized
for the determination of hydrazine in real samples.
PMID- 28415402
TI - Fattigation-platform theranostic nanoparticles for cancer therapy.
AB - A new conceptual nanoparticle consisting of a silica-coated iron oxide magnetic
core and a fattigation-based biocompatible shell with oleic acid and hydrophilic
protein (gelatin). The prepared particle can be a useful theranostics platform
material for diagnostic imaging and as a drug delivery system. Oleic acid and
gelatin were conjugated on the silica-coated magnetic nanoparticle surface to
provide three primary functionalities: 1) enhancing biocompatibility and
solubility in aqueous solution and providing the ability to incorporate
hydrophobic chemical drugs into the shell for delivery, 2) improving treatment
response magnetic monitoring as a diagnostic agent with low nanotoxicity, and 3)
increasing anticancer efficacy owing to the controlled release of the
incorporated drug in cells and in an animal model. We prepared magnetic-silica
nanoparticles with super-paramagnetic properties, which are utilized as a T2
weighted magnetic resonance imaging agent. After formation of an oleic acid
gelatin shell, the prepared materials exhibited high loading capacity for a
hydrophobic anticancer drug (paclitaxel). Our particle platform system exhibited
higher therapeutic efficacy and lower toxicological effects in vitro and in an in
vivo cancer model than a clinically available chemo-drug (Taxol(r)). Our findings
strongly suggest that this nanoparticle system can serve as a platform for cancer
therapy by the incorporation of chemical drugs.
PMID- 28415404
TI - Macrophage phagocytosis of biomedical Mg alloy degradation products prepared by
electrochemical method.
AB - Biomedical Mg alloy is promising for its widespread use clinically. In vitro and
in vivo studies showed that the degradation products of biomedical Mg alloy were
composed of O, P, Ca, Mg and other alloying elements. However, little is known
about the metabolism of the degradation products. In this study, the in vitro
macrophage phagocytosis of the degradation products of a biomedical Mg-Nd-Zn-Zr
alloy was directly observed. This result affirms the necessity to investigate the
long-term fate of Mg alloy degradation products in physiological environments.
Besides, an electrochemical method was proposed to prepare enough amount of
degradation products in vitro efficiently.
PMID- 28415403
TI - Design and synthesis of reduced graphene oxide based supramolecular scaffold: A
benign microbial resistant network for enzyme immobilization and cell growth.
AB - The present study describes the synthesis, characterization and biological
application of reduced graphene oxide - chitosan (GC) based benign supramolecular
scaffold (SMS). Various spectroscopic and microscopic analyses established the
supramolecular interaction in between rGO and chitosan. The active performance of
the developed material towards microbial resistivity, in vitro cell growth and as
a scaffold for enzyme immobilizing matrix illustrates its unique implementation.
Immobilization of polyphenol oxidase (PPO) onto GC lowers the Michaelis- Menten
constant (Km) value and facilitates to achieve maximum velocity at low substrate
concentration. Importantly GC shows no noteworthy cytotoxicity towards Wistar rat
macrophage cells. Moreover, incorporation of gold nanoparticle further
strengthens the microbial resistance properties of GC as well as improves its
biocompatibility by reducing cytotoxicity. Therefore these unique features may
inspire it to appear in large scale for industrial utilization.
PMID- 28415405
TI - Incorporation of glass-reinforced hydroxyapatite microparticles into poly(lactic
acid) electrospun fibre mats for biomedical applications.
AB - Tissue engineering is constantly evolving towards novel materials that mimic the
properties of the replaced injured tissue or organ. A hybrid electrospun membrane
of electroactive poly(l-acid lactic) (PLLA) polymer with glass reinforced
hydroxyapatite (Bonelike(r)) microparticles placed among the polymer fibres in a
morphology like "islands in the sea" was processed. The incorporation of 60 to
80wt% Bonelike(r) bone grafts granules with <=150MUm into the polymer solution
lead to an amorphous polymeric fibre membranes, and a decrease of the average
polymer fibre diameter from 550+/-150nm for neat PLA down to 440+/-170nm for the
hybrid composite. The presence of Bonelike(r) in the polymer mats reduced the
activation energy for thermal degradation from 134kJ.mol-1, obtained for the neat
PLLA membranes down to 71kJ.mol-1, calculated for the hybrid composite membranes.
In vitro cell culture results suggest that the developed processing method does
not induce cytotoxic effects in MG 63 osteoblastic cells, and creates an
environment that enhances cell proliferation, when compared to the neat PLLA
membrane. The simplicity and scalability of the processing method suggests a
large application potential of this novel hybrid polymer-microparticles fibre
membranes for bone regenerative medicine.
PMID- 28415406
TI - PCL foamed scaffolds loaded with 5-fluorouracil anti-cancer drug prepared by an
eco-friendly route.
AB - This study describes a new preparation method, which combines freeze drying and
supercritical CO2 foaming approaches, for the preparation of drug delivery
scaffolds of polycaprolactone loaded with 5-fluorouracil, an anti-cancer drug,
with low solubility in scCO2. It is a principal objective of this work to design
a scCO2 strategy to reduce 5-Fu solubility limitations in its homogeneous
distribution into a PCL scaffold through the design of an innovative processing
method. The design of this process is considered valuable for the development of
clean technology in pharmacy and medicine, since most of the active agents have a
null solubility in scCO2.Supercritical CO2 is used as a blowing agent to induce
polymer foaming by means of the low temperature pressure quench process. The
resulting samples have been prepared under different operational conditions
focused on enhancing the performance of the release process. In this case, design
of experiments (DOE) was considered for a more comprehensive and systematic
optimization of the product. In particular, drug amount, equals to 4.8 or 9.1wt%,
process temperature, of 45 or 50 degrees C and depressurization rate, equals to
0.1MPas-1 or 2MPas-1 were selected as the factors to be investigated by a three
factor at two-level full factorial design. Samples were characterized to
establish porosity data, drug loading percentage and, especially, release profile
chromatographically monitored. Results from DOE have concluded which are the best
samples providing a sustained drug release for several days, which may be of
great interest to develop materials for tissue engineering and sustained release
applications.
PMID- 28415407
TI - Formulation by design based risperidone nano soft lipid vesicle as a new strategy
for enhanced transdermal drug delivery: In-vitro characterization, and in-vivo
appraisal.
AB - The present study was designed to formulate and optimize transdermal risperidone
soft lipid vesicles. The formulation optimized with phospholipid, safranal and
ethanol were incorporated as permeation and absorption enhancers. The optimized
risperidone soft lipid vesicle was further evaluated for skin irritation study,
in-vivo pharmacokinetic study and locomotor activity. Three factor three level
Box-Behnken design (BBD) was used to statistically optimize soft lipid vesicle
using safranal (A), ethanol (B)and phospholipid (C) as independent variable,
while their effect was observed for vesicle size (Y1), entrapment efficiency (Y2)
and flux (Y3). The optimized risperidone soft lipid vesicle (Ris-opt) showed
nanometric vesicle size, high entrapment efficiency and marked enhancement in
transdermal flux. The extent of absorption from Ris-opt was greater when compared
to oral suspension with relative bioavailability of 177%. The histopathological
evaluation revealed developed formulation did not showed skin irritation compared
to standard irritant. The significant findings presented here encourage further
studies with risperidone soft lipid vesicles for treatment of schizophrenia.
PMID- 28415408
TI - Role of cellulose functionality in bio-inspired synthesis of nano bioactive
glass.
AB - In search of abundant cheaper natural polymer for bio-inspired bioactive glass
nanoparticles synthesis, cellulose and its derivatives have been considered as a
template. Different templates explored in the present studies are pure cellulose,
methyl cellulose and amine grafted cellulose. To the best of our knowledge, for
the first time of the considered templates, pure cellulose and amine grafted
cellulose results in in situ nano particulate composite formation while
interestingly methyl cellulose proves to be an excellent sacrificial template for
the synthesis of uniform bioglass nanoparticles of diameter in the range of 55nm.
Further, viscoelastic measurements were carried out using dynamic mechanical
analyzer. Herein, an attempt has been made to establish structure-mechanical
relationship based on the templates. Moreover, in vitro bioactivity is also
observed to be affected by the nature of the template molecule used for the
synthesis of bioactive glass.
PMID- 28415409
TI - In vitro antiherpes effect of C-glycosyl flavonoid enriched fraction of Cecropia
glaziovii encapsulated in PLGA nanoparticles.
AB - In this work is reported a novel and promising approach for the preparation of C
glycosylflavonoid enriched fraction of Cecropia glaziovii (EFF-Cg) loaded PLGA
nanoparticles (NP) with antiherpes properties. The purpose of this study was to
evaluate and to compare the effect of two nonionic surfactants (poloxamer 188
(PLU) and polyvinyl alcohol (PVA)), and also an emulsion stabilized by solid
particles of cellulose nanocrystal (CNC) in place of surfactants. The
characterization of these nanoparticles was in terms of size, polydispersity
index, zeta potential, morphology, thermogravimetric analysis (TGA), loading
capacity and percent yield. Since TGA analysis revealed thermo stability
especially for NP-PLU, this formulation was selected for the evaluation of drug
release profile, cytotoxicity and antiherpes activity. The drug delivery profile
demonstrated a sustained release through the polymer structure and a significant
reduction of the polymer molecular weight at 21-day period. The cytotoxicity of
these nanoparticles was determined on Vero cells, and the selected formulation
did not exhibit cytotoxicity even at the highest tested concentration. The
results demonstrated a potential antiherpetic effect of the EFF-Cg loaded NP at
48h of testing. In summary, EFF-Cg loaded NP exhibited a promising system for the
effective drug delivery in the treatment of herpes infections.
PMID- 28415410
TI - Biodegradable polyurethane micelles with pH and reduction responsive properties
for intracellular drug delivery.
AB - Polyurethane micelles with disulfide linkage located at the interface of
hydrophilic shell and hydrophobic core (PU-SS-I) have been shown enhanced drug
release profiles. However, the payloads could not be released completely. The
occurrence of aggregation of hydrophobic cores upon shedding hydrophilic PEG
coronas was considered as the reason for the incomplete release. To verify the
above hypothesis and to develop a new polyurethane based micelles with dual
stimuli respond properties and controllable location of pH and reduction
responsive groups in the PU main chains, a tertiary amine was incorporated into
the hydrophobic core PU-SS-I, which resulted polyurethane with both reduction and
pH sensitive properties (PU-SS-N). Biodegradable polyurethane with only disulfide
linkages located between the hydrophilic PEG segment and the hydrophobic PCL
segments (PU-SS-I) and polyurethane with only pH sensitive tertiary amine at the
hydrophobic core (PU-N-C) were used as comparisons. Paclitaxel (PTX) was chosen
as mode hydrophobic drug to evaluate the loading and redox triggered release
profiles of the PU micelles. It was demonstrated that PU-SS-N micelles
disassembled instantly at the presence of 10mM GSH and at an acidic environment
(pH=5.5), which resulted the nearly complete release (~90%) of the payloads
within 48h, while about ~70% PTX was released from PU-SS-I and PU-SS-N micelles
at neutral environment (pH=7.4) with the presence of 10mM GSH. The rapid and
complete redox and pH stimuli release properties of the PU-SS-N nanocarrier will
be a promising anticancer drug delivery system to ensure sufficient drug
concentration to kill the cancer cells and to prevent the emergency of MDR. The
in vitro cytotoxicity and cell uptake of the PTX-loaded micelles was also
assessed in H460 and HepG2 cells.
PMID- 28415411
TI - Quality by Design approach for an in situ gelling microemulsion of Lorazepam via
intranasal route.
AB - The present study illustrates the application of the concept of Quality by Design
for development, optimization and evaluation of Lorazepam loaded microemulsion
containing ion responsive In situ gelator gellan gum and carbopol 934. A novel
approach involving interactions between surfactant and polymer was employed to
achieve controlled drug release and reduced mucociliary clearance. Microemulsion
formulated using preliminary solubility study and pseudo ternary phase diagrams
showed significantly improved solubilization capacity of Lorazepam with 54.31+/
6.07nm droplets size. The effect of oil to surfactant/cosurfactant ratio and
concentration of gelling agent on the drug release and viscosity of microemulsion
gel (MEG) was evaluated using a 32 full factorial design. The gel of optimized
formulation (MEG1) showed a drug release up to 6h of 97.32+/-1.35% of total drug
loaded. The change in shear-dependent viscosity for different formulations on
interaction with Simulated Nasal Fluid depicts the crucial role of surfactant
polymer interactions on the gelation properties along with calcium ions binding
on the polymer chains. It is proposed that the surfactant-polymer interactions in
the form of a stoichiometric hydrogen bonding between oxyethylene and carboxylic
groups of the polymers used, provides exceptional ME stability and adhesion
properties. Compared with the marketed formulation, optimized MEG showed improved
pharmacodynamic activity. Ex vivo diffusion studies revealed significantly higher
release for MEG compared to microemulsion and drug solution. MEG showed higher
flux and permeation across goat nasal mucosa. According to the study, it could be
concluded that formulation would successfully provide the rapid onset of action,
and decrease the mucociliary clearance due to formation of in situ gelling
mucoadhesive system.
PMID- 28415412
TI - Graphene oxide modified single-use electrodes and their application for
voltammetric miRNA analysis.
AB - The modification of graphene oxide (GO) onto the surfaces of chemically activated
pencil graphite electrodes (PGEs) was performed herein, and then these electrodes
were applied for the first time on voltammetric monitoring of miRNAs. The
specific recognition of miRNA-34a, which has been related to Alzheimer disease,
was explored in the presence of DNA-RNA hybridization by using CA/GO/PGEs in
combination with differential pulse voltammetry (DPV) technique. The
characterization of CA/GO/PGE was investigated by cyclic voltammetry (CV),
electrochemical impedance spectroscopy (EIS), and scanning electron microscopy
(SEM). The effect of GO concentration, DNA probe concentration and miRNA-34a
concentration upon to biosensor response was optimized, and accordingly, the
selectivity of miRNA-34a biosensor was tested under the optimum conditions.
PMID- 28415413
TI - Development and characterization of the cisplatin loaded nanofibers for the
treatment of cervical cancer.
AB - A small scale study was carried out to investigate the therapeutic efficacy
cisplatin loaded poly-caprolactone/chitosan composite electrospun nanofibers for
local chemotherapy of cervical cancers in mice. The prepared nanofibers had shown
the sustained release pattern up to one month. Prepared nanofibers were found to
have greater mucoadhesive strength. An orthotopic cervical cancer model was
established by inducing the EAC cell lines in the vaginal mucosa at cervix region
of the mice. Intravaginal administration of the cisplatin loaded nanofibers
showed lesser % cell viability as compared to the plain drug. In vivo studies
showed a better anti-tumour efficacy of prepared nanofibers in animals at 14th
and 21st after the beginning of treatment. Therefore the technique of
electrospinning provides a favourable approach for the targeted delivery of the
anti-cancer drug via vaginal route against cervical cancer.
PMID- 28415414
TI - Bionanocomposite systems based on montmorillonite and biopolymers for the
controlled release of olanzapine.
AB - Olanzapine (OLZ) is a drug that is used in the treatment of schizophrenia and
other psychoses, and it belongs to the thienobenzodiazepine class. The OLZ
molecule has low solubility decreasing bioavailability, but has high permeability
in membrane biological being classified as a Class II drug substance according to
the Biopharmaceutics Classification System. It was reported many side effects of
administering OLZ orally. So, in order to increase the bioavailability of drug
and possibly reducing some of side effects, this paper proposes a new material
able to controllably release the drug in the body. To control the dissolution
rate, this work proposes a system that incorporates the drug into montmorillonite
(MMT) dispersed in a mixture of alginate (ALG) and xanthan gum (XG) biopolymers.
The proposed hybrids and bionanocomposites were characterized by several
physicochemical techniques, including XRD, IR-ATR, TG DTA, SEM-EDS and HPLC. The
characterization data confirmed the intercalation of the OLZ into the MMT by the
ion exchange process, as well as the interaction of the MMT-OLZ with the
biopolymers. The release test, conducted under various pH conditions, showed that
the proposed system exhibited a more controlled drug release than commercial
tablets, indicating that the ALG-XG/MMT-OLZ bionanocomposite can act as a
controlled release system for OLZ.
PMID- 28415415
TI - Curcumin-loaded polysaccharide nanoparticles: Optimization and anticariogenic
activity against Streptococcus mutans.
AB - Curcumin was loaded into different polysaccharide nanoparticles chitosan,
alginate and starch, using the desolvation method. Curcumin-loaded nanoparticles
exhibited enhanced solubility in aqueous solutions comparing with free curcumin.
Effects of formulation parameters such as curcumin concentration and different
volumes of ethanolic solution were affected the particle size and loading
efficiency. Under optimum conditions, curcumin-loaded chitosan, starch and
alginate nanoparticles with mean particles sizes of 66.3, 61.1 and 78.8nm, and
maximum loading efficiencies of 11.9%, 14.3% and 13.35% were achieved,
respectively. Additionally, the minimum inhibitory concentration for chitosan,
starch and alginate nanoparticles against the microorganism, Streptococcus
mutans, were 0.114, 0.204 and 0.204mg/mL, respectively. Curcumin was observed to
release from nanoparticles under physiological pH over a period of 96h. The
effect of curcumin-loaded nanoparticles on S. mutans biofilms was assessed on
dental models. According to the results, curcumin-loaded chitosan nanoparticles
hold promises for being used in dental decay fighting products.
PMID- 28415416
TI - In vitro and in vivo corrosion, mechanical properties and biocompatibility
evaluation of MgF2-coated Mg-Zn-Zr alloy as cancellous screws.
AB - Magnesium (Mg) and its alloys as biodegradable materials have received much
attention in the orthopedics applications; however, the corrosion behavior of
these metals in vivo remains challenging. In this work, a dense and nanoscale
magnesium fluoride (MgF2) coating was deposited on the surface of Mg-Zn-Zr (MZZ)
alloy cancellous screw. The MZZ cancellous screw with MgF2 coating maintained an
integrated shape and high yield tensile stress after 30days immersion in SBF,
comparing with the bare screw. Hydrogen releasing rate of the MZZ samples was
suppressed at a lower level at the initial stage, which is in favour of the
adhesion of the cells. And in vivo experiments indicated that MgF2-coated MZZ
screws presented advantages in cytocompatibility, osteoconductivity and
osteogenesis of cancellous bone in rabbits. Corrosion rate in vivo perfusion
environment increased very slowly with time in long-term study, which was an
opposite trend in vitro static immersion test. Moreover, maximum corrosion rate
(CRmax), a critical calculation method of corrosion rate was introduced to
predict fracture regions of the sample. The MZZ alloy with MgF2 coating possesses
a great potential for clinical applications for internal fracture fixation
repair.
PMID- 28415417
TI - Porous 45S5 Bioglass(r)-based scaffolds using stereolithography: Effect of
partial pre-sintering on structural and mechanical properties of scaffolds.
AB - Scaffolds made from 45S5 Bioglass(r) ceramic (BG) show clinical potential in bone
regeneration due to their excellent bioactivity and ability to bond to natural
bone tissue. However, porous BG scaffolds are limited by their mechanical
integrity and by the substantial volume contractions occurring upon sintering.
This study examines stereolithographic (SLA) methods to fabricate mechanically
robust and porous Bioglass(r)-based ceramic scaffolds, with regular and
interconnected pore networks and using various computer-aided design
architectures. It was found that a diamond-like (DM) architecture gave scaffolds
the most controllable results without any observable closed porosity in the fired
scaffolds. When the pore dimensions of the DM scaffolds of the same porosity
(~60vol%) were decreased from 700 to 400MUm, the compressive strength values
increased from 3.5 to 6.7MPa. In addition, smaller dimensional shrinkage could be
obtained by employing partially pre-sintered bioglass, compared to standard 45S5
Bioglass(r). Scaffolds derived from pre-sintered bioglass also showed marginally
improved compressive strength.
PMID- 28415418
TI - UV-assisted treatment on hydrophobic acrylic IOLs anterior surface with
methacryloyloxyethyl phosphorylcholine: Reducing inflammation and maintaining low
posterior capsular opacification properties.
AB - In order to enhance the surface biocompatibility of hydrophobic acrylic
intraocular lenses (IOLs), the anterior surface was modified through graft
polymerization with methacryloyloxyethyl phosphorylcholine (MPC) initiated by
ultraviolet radiation. Chemical changes on the IOL surface were characterised by
X-ray photoelectron spectroscopy (XPS) to confirm the covalent binding of MPC.
Field emission scanning electron microscopy (FESEM) and atomic force microscopy
(AFM) analysis were used to characterise the morphological changes to the IOL
surface. Static water contact angle (WCA) measurements showed that the
hydrophilicity of the anterior surface was enhanced after grafting with MPC. The
surface biocompatibility of the untreated and Anterior UV-MPC IOLs was compared
with the adhesion behaviour of macrophages in vitro. The degree of posterior
capsule opacification (PCO) of untreated, anterior treated, and posterior treated
IOLs was evaluated by observing the behaviour of lens epithelial cells (LECs)
between the IOL optic portion and type IV collagen. Results suggest that the MPC
modified anterior surface resisted the attachment of macrophages. However, MPC
grafted onto the posterior surface enhanced the migration of LECs between the IOL
optic and type IV collagen, which may result in severe PCO. In conclusion, our
Anterior UV-MPC IOLs may reduce postoperative inflammation while maintaining the
low PCO rates of hydrophobic acrylic IOLs.
PMID- 28415419
TI - LSP/MAO composite bio-coating on AZ80 magnesium alloy for biomedical application.
AB - A composite bio-coating was fabricated on AZ80 magnesium (Mg) alloy by using
micro-arc oxidation (MAO) under the pretreatment of laser shock peening (LSP) in
order to improve the bio-corrosion resistance and the mechanical integrity. LSP
treatment could induce grain refinement and compressive residual stress field on
the surface of material. MAO bio-coating was grown in alkaline electrolyte with
hydroxyapatite (HA, Ca10(PO4)6(OH)2) to improve the biological properties of the
material. The microstructure, element and phase composition for untreated based
material (BM) and treated samples (LSP layer, MAO bio-coating and LSP/MAO
composite bio-coating) were investigated by transmission electron microscopy
(TEM), scanning electron microscope (SEM), energy dispersion spectroscopy (EDS)
and X-ray diffraction (XRD). Electrochemical tests and slow strain rate tensile
(SSRT) tests were used to evaluate the corrosion resistance and the stress
corrosion susceptibility in simulated body fluid (SBF). The results indicated
that LSP/MAO composite bio-coating can not only improve the corrosion resistance
of Mg alloy substrate evidently but also increase the mechanical properties in
SBF compared to LSP layer and MAO bio-coating. Mg alloy treated by LSP/MAO
composite technique should be better suited as biodegradable orthopedic implants.
PMID- 28415420
TI - In-vitro cell adhesion and proliferation of adipose derived stem cell on
hydroxyapatite composite surfaces.
AB - The goal of this work was to enhance the mechanical strength and fracture
toughness of brittle hydroxyapatite (HAP) by reinforcing it with nanocomposites
such as graphene oxide (GO), carbon nanotubes (CNT) and Titania. The goal was
also to evaluate the cytotoxicity and the cellular adhesion/proliferation of
these composites. The composites were characterized for their crystallinity,
functionality, morphology and mechanical properties. Altering the composition by
adding 1wt% GO and CNT significantly altered the wettability, hardness and
roughness. Further, X-ray diffraction (XRD), Fourier transform infrared
spectroscopy (FITR) and X-ray photoelectron spectroscopy (XPS) results confirm
the crystal structure, bulk chemical composition and surface elemental
composition respectively of the composites. The bulk hardness of HAP with CNT was
significantly higher than that of HAP. The wettability of HAP with GO was
significantly lower than that of HAP with GO and Titania. Adipose Derived Stem
Cells (ADSCs) were used for this study to evaluate cytotoxicity and viability.
HAP with CNT and HAP with CNT and Titania were found to be least cytotoxic
compared to other composites as evaluated by Lactate Dehydrogenase (LDH) assay
and alamarBlue assay. ADSC adhesion and proliferation was investigated after 1, 4
and 7days of culture using fluorescence microscopy. All the composites nurtured
ADSC adhesion and proliferation, however, distinct morphological changes were
observed by using Scanning Electron Microscopy (SEM). Overall, these composites
have the potential to be used as bone graft substitutes.
PMID- 28415421
TI - Simple synthesis of hierarchical AuPt alloy nanochains for construction of highly
sensitive hydrazine and nitrite sensors.
AB - Herein, a single-step co-reduction aqueous route was designed for preparation of
hierarchical AuPt alloy nanochains, firstly using amprolium hydrochloride as a
new stabilizing agent and structure-director. The morphology, structure,
composition, and size of the products were characterized by a series of
technique. The growth mechanism of AuPt nanochains was discussed in details. The
AuPt nanochains modified glassy carbon electrode showed the improved analytical
performances for determination of nitrite and hydrazine. The linear ranges of
nitrite are 0.5-366.4MUM and 466.4-2666.4MUM for the two segments, and the
detection limit is 0.03MUM (S/N=3). The linear ranges of hydrazine are 5.0
116.4MUM and 166.4-2666.4MUM for the two segments, along with the low detection
limit of 0.26MUM (S/N=3). The performances of AuPt nanochains were superior to
those of individual Pt and Au nanoparticles. It is ascribed to the specific
hierarchical structures and synergistic effects of the bimetals.
PMID- 28415422
TI - Synthesis and characterization of redox-sensitive heparin-beta-sitosterol
micelles: Their application as carriers for the pharmaceutical agent,
doxorubicin, and investigation of their antimetastatic activities in vitro.
AB - Although there are several clinical attempts to treat tumors at the primary site,
only few therapies can inhibit the spread of metastatic cancers. In this study,
we synthesized redox-sensitive heparin-beta-sitosterol micelles that show
antimetastatic activity. Proton nuclear magnetic resonance and Fourier transform
infrared analyses confirmed the formation of bioreducible heparin-beta-sitosterol
(bHSC) conjugates, whereas dynamic light scattering was used to measure the
particle size and zeta potential. Both 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and flow cytometry assays confirmed the low toxicity
of the synthesized micelles. Doxorubicin (Dox) was encapsulated via the dialysis
method, and its loading and encapsulation efficiencies were 16.49+/-1.2% and
58.47+/-1.87%, respectively. An in vitro release study showed that approximately
89% and 52% of Dox were released after 48h in the presence and absence of reduced
glutathione, respectively. The hemocompatibility and antimetastatic effects of
bHSC were evaluated using the hemolysis and scratch assays, respectively. F-Actin
fluorescence microscopy showed that heparin- and bHSC-treated HeLa cells had
poorly oriented stress fibers. In summary, the synthesized bHSC micelles are good
candidates as drug delivery systems owing to their low toxicity, excellent
hemocompatibility, and antimetastatic effects.
PMID- 28415423
TI - Investigation of antifouling and disinfection potential of chitosan coated iron
oxide-PAN hollow fiber membrane using Gram-positive and Gram-negative bacteria.
AB - Chitosan coated iron oxide nanoparticles were impregnated into polyacrylonitrile
based hollow fiber membrane. The molecular weight cut off was varied in the range
of 120 to 145kDa with the concentration of nanoparticles. Incorporation of
nanoparticles improved the permeability, mechanical property and hydrophilicity
of the membrane. The contact angle of the membrane decreased from 80 degrees to
51 degrees and the permeability increased by 31% at 0.5wt% nanoparticles
concentration. The antibacterial and antifouling property of the membrane were
investigated with two biofilm causing Gram positive and Gram negative bacteria.
The damage of cell membrane was directly confirmed by release of cellular
constituent absorbing in 260nm. The cellular deformation on the membrane surface
was evident by direct microscopic observation in FESEM. This damage was likely
caused by electrostatic interaction between NH3+ group of nanoparticles and
anionic components of phosphoryl group of bacteria. The hollow fiber membrane
shows promising antibiofouling property even after long experimental run as
evident by 95% flux recovery ratio. The effect of operating conditions on
rejection and flux profile was investigated during long experimental run. The
result indicated that there was no detectable iron in the permeate sample that
could impose adverse health hazard.
PMID- 28415424
TI - Development of strong, biodegradable and highly elastomeric polycitrate-gelatin
hybrid polymer with enhanced cellular biocompatibility.
AB - Native human tissues possess incomparable biological performance due to their
strong and viscoelastic mechanical properties, and biocompatible compositions.
Herein, by a thermal polymerization and solvent hybridization method, we develop
biomimetic polycitrate-gelatin hybrid polymers (PC-GT) with strong mechanical
properties and tailored elastomeric behavior for tissue regeneration
applications. The incorporation of gelatin significantly enhanced the mechanical
properties and cellular biocompatibility of PC. PC-GT hybrids demonstrated the
135 times (from 7.5 to 1015MPa) and 11 times (from 4 to 46MPa) improvement for
the elastomeric modulus and tensile strength respectively as compared with PC
elastomers, while showing controlled stretchable and elastomeric behavior. In
addition, PC-GT hybrids significantly improved the fibroblasts (L929) attachment
and proliferation, suggesting their high biocompatibility. This study may provide
a novel strategy to design biocompatible hybrid polymers with strong and
elastomeric behavior for tissue regeneration and stretchable electronic devices
applications.
PMID- 28415425
TI - "Click" access to multilayer functionalized Au surface: A terpyridine patterning
example.
AB - This work is focused on self-assembled monolayers (SAMs) fabrication, using two
types of Au surfaces, by subsequent attachment of different layers in order to
develop a stable platform consisting of covalent multilayer functionalized gold
surfaces. The key step in the construction of SAMs is the covalent linkage to the
gold surface, via an amino-thiol derivative, of a cyclooctyne unit exhibiting
strained triple bonds which react fast (catalysts are not needed) and
quantitatively with organic azides and enable the introduction of various
chemical functionalized entities on the gold surface. The versatility of the
system is demonstrated by the reaction of the cyclooctyne decorated gold surface
with an azide functionalized terpyridine followed by step by step complexation
with Fe(II) and another terpyridine unit resulting into a multilayer covered gold
surface. The Au surfaces were characterized by XPS to determine the chemical
composition of the resulting SAMs. SPR was applied for real-time monitoring of
the molecular interactions that occurred on the Au surface for each deposited
layer. DPN was used to direct pattern the terpyridine-ink on a pre-functionalized
AuIDE electrode. The AFM topology resulted from DPN and PEIS demonstrated metal
coordinating ligand of Fe(II)-Terpy.
PMID- 28415426
TI - Influence of Dy in solid solution on the degradation behavior of binary Mg-Dy
alloys in cell culture medium.
AB - Rare earth element Dy is one of the promising alloying elements for magnesium
alloy as biodegradable implants. To understand the effect of Dy in solid solution
on the degradation of Mg-Dy alloys in simulated physiological conditions, the
present work studied the microstructure and degradation behavior of Mg-Dy alloys
in cell culture medium. It is found the corrosion resistance enhances with the
increase of Dy content in solid solution in Mg. This can be attributed to the
formation of a relatively more corrosion resistant Dy-enriched film which
decreases the anodic dissolution of Mg.
PMID- 28415428
TI - The effect of sliding onto the metal-electrolyte interface: Studying model
parameter modifications by means of EIS.
AB - Several problems are associated with corrosion-wear occurring on metal-on-metal
hip implants made out of cobalt-chromium based alloys. Low temperature
carburizing, a process that creates a hard and corrosion resistant diffused layer
in Cobalt-Chromium-Molybdenum (CoCrMo) alloys, known as S-phase, may be a
possible solution towards mitigating these problems. In this work, static- and
tribo-corrosion testing involving an alumina versus CoCrMo (untreated and
carburized) were conducted in Ringer's solution. Electrochemical impedance
spectroscopy was used to compare impedance plots attained before and after
sliding so as to understand how the metal-electrolyte interface is affected by
rubbing. Both untreated and carburized CoCrMo experienced extensive reduction in
corrosion resistance following sliding wear damage such that one should expect a
considerably deteriorated performance of both surfaces in a tribocorrosion
application. The structure of the interface was relatively unaffected after
sliding at the equilibrium and passive potentials. This implies that the layers
making up the interface before sliding were still present after sliding. However,
their properties changed - the interface's real resistance dropped while its
capacitance increased. The former was linked to a weaker, damaged passive film
while the latter was linked to accumulation of wear debris and corrosion
products.
PMID- 28415427
TI - Surface physical chemistry properties in coated bacterial cellulose membranes
with calcium phosphate.
AB - Bacterial cellulose has become established as a new biomaterial, and it can be
used for medical applications. In addition, it has called attention due to the
increasing interest in tissue engineering materials for wound care. In this work,
the bacterial cellulose fermentation process was modified by the addition of
chondroitin sulfate to the culture medium before the inoculation of the bacteria.
The biomimetic process with heterogeneous calcium phosphate precipitation of
biological interest was studied for the guided regeneration purposes on bacterial
cellulose. FTIR results showed the incorporation of the chondroitin sulfate in
the bacterial cellulose, SEM images confirmed the deposition of the calcium
phosphate on the bacterial cellulose surface, XPS analysis showed a selective
chemical group influences which change calcium phosphate deposition, besides, the
calcium phosphate phase with different Ca/P ratios on bacterial cellulose surface
influences wettability. XTT results concluded that these materials did not affect
significantly in the cell viability, being non-cytotoxic. Thus, it was produced
one biomaterial with the surface charge changes for calcium phosphate deposition,
besides different wettability which builds new membranes for Guided Tissue
Regeneration.
PMID- 28415429
TI - Aminated carbon-based "cargo vehicles" for improved delivery of methotrexate to
breast cancer cells.
AB - The purpose of study was to conjugate and evaluate methotrexate with C60
fullerenes and multi-walled carbon nanotubes (MWCNTs) for better drug delivery to
cancer cells, and also to compare these two systems. C60-fullerenes and MWCNTs
were functionalized by 1,3-dipolar cycloaddition using glycine and
paraformaldehyde. Methotrexate (MTX) was esterified and conjugated to the
functionalized carbon-based carriers. The conjugates were characterized for
micromeritics and drug conjugation. The systems were evaluated for drug release
in various pH, MTT cytotoxicity assay, protein binding, cellular uptake,
haemolytic profile and pharmacokinetics. Spectroscopic studies confirmed the
successful conjugation of drug to the aminated carbon-based carriers. The
developed systems released more drug at the pH of cancer cells to that of the pH
of plasma. The carriers were compatible with erythrocytes and offered substantial
cytotoxicity. Better cellular uptake was confirmed by confocal laser scanning
microscopy. C60-fullerenes/MWCNTs modulated the pharmacokinetic profile of drug
in desired manner, resulting in better retention and compartment availability.
However, the results from C60-fullerenes were observed to be better than that
from MWCNTs. The present findings established the potential of carbon-based
aminated nanocarriers for delivery of methotrexate in safer and effective manner.
PMID- 28415430
TI - X-ray visible and doxorubicin-loaded beads based on inherently radiopaque
poly(lactic acid)-polyurethane for chemoembolization therapy.
AB - The aim of current study was to develop drug-loaded polymeric beads with
intrinsic X-ray visibility as embolic agents, targeting for noninvasive
intraoperative location and postoperative examination during chemoembolization
therapy. To endow polymer with inherent radiopacity, 4,4'-isopropylidinedi-(2,6
diiodophenol) (IBPA) was firstly synthesized and employed as a contrast agent,
and then a set of radiopaque iodinated poly(lactic acid)-polyurethanes (I-PLAUs)
via chain extender method were synthesized and characterized. These I-PLAU
copolymers possessed sufficient radiopacity, in vitro non-cytotoxicity with human
adipose-derived stem cells, and in vivo biocompatibility and degradability in
rabbit model via intramuscular implantation. Doxorubicin (DOX), as a
chemotherapeutic agent, was further incorporated into I-PLAU beads via a double
emulsification (W/O/W) method. For drug release, two ratios of DOX-loaded I-PLAU
beads exhibited calibrated size (200-550MUm), porous internal structure, good X
ray visibility, evenly drug loading as well as tunable drug release. A
preliminary test on in vitro tumor cell toxicity demonstrated that the DOX-loaded
I-PLAU beads performed efficient anti-tumor effect. This study highlights novel X
ray visible drug-loaded I-PLAU beads used as promising embolic agents for non
invasive in situ X-ray tracking and efficient chemotherapy, which could bring
opportunities to the next generation of multifunctional embolic agents.
PMID- 28415431
TI - In vitro cytotoxicity study of dual drug loaded chitosan/palladium nanocomposite
towards HT-29 cancer cells.
AB - Conjugated drug delivery has gained immense interest due to the possibility of
overcoming the resistance of cancer cells to a specific drug when treated using
it for a period of time. In the present study, CS/Pd nanocomposite has been
prepared using cost effective chemical reduction method and has been used for the
delivery of curcumin (CUR) and 5-Fluorouracil (5-FU) separately and in a
conjugated form. The prepared nanocomposite before and after drug encapsulation
have been studied using various characterization techniques. The release of drugs
from the nanocomposite with respect to time has been analyzed and the release
kinetics has also been studied. The release profile is mostly seen to adhere to
zero order kinetics which represents the constant release of drugs from drug
delivery system. This is the most favored release kinetic as this leads to the
prolonged release of the drug, thus leading to a reduction in the number of doses
administered. The cytotoxicity of the drug loaded nanocomposites on colon cancer
cells has been studied, which shows the effectiveness of the composite system
towards successfully inhibiting the growth of cancer cells.
PMID- 28415432
TI - Fabrication of dicalcium phosphate dihydrate-coated beta-TCP granules and
evaluation of their osteoconductivity using experimental rats.
AB - beta-Tricalcium phosphate (beta-TCP) has attracted much attention as an
artificial bone substitute owing to its biocompatibility and osteoconductivity.
In this study, osteoconductivity of beta-TCP bone substitute was enhanced without
using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is
known to possess the highest solubility among calcium phosphates, was coated on
beta-TCP granules by exposing their surface with acidic calcium phosphate
solution. The amount of coated DCPD was regulated by changing the reaction time
between beta-TCP granules and acidic calcium phosphate solution. Histomorphometry
analysis obtained from histological results revealed that the approximately
10mol% DCPD-coated beta-TCP granules showed the largest new bone formation
compared to DCPD-free beta-TCP granules, approximately 2.5mol% DCPD-coated beta
TCP granules, or approximately 27mol% DCPD-coated beta-TCP granules after 2 and
4weeks of implantation. Based on this finding, we demonstrate that the
osteoconductivity of beta-TCP granules could be improved by coating their surface
with an appropriate amount of DCPD.
PMID- 28415433
TI - Multifunctional nanospheres for co-delivery of methotrexate and mild hyperthermia
to colon cancer cells.
AB - A multifunctional nanomedicine platform was designed and evaluated for efficient
colon cancer therapy by a combinatorial therapeutic approach based on a
chemotherapeutic drug and mild hyperthermia. Advantage was taken from the dual
role of methotrexate (MTX), as folate receptor-targeting, overexpressed in tumor
cells, and as anticancer drug. Incorporation of superparamagnetic iron oxide
nanoparticles (SPIONs) allows to heat cancer cells externally through an
alternating magnetic field. The developed nanocarrier was based on polyethylene
glycol-polylactic acid (PEG-PLA) nanospheres to improve biocompatibility,
enhancing their targeting by prolonging blood circulation time. By an emulsion
evaporation method the nanospheres were produced and then characterized for size
distribution, zeta-potential, in vitro drug release profile and cellular studies.
The co-delivery of MTX and SPIONs on PEG-PLA nanospheres resulted in nanocarriers
with a size of 160nm in diameter, a polydispersity index below 0.2 and a zeta
potential of ca. -18mV. Multifunctional nanospheres were monodisperse and stable
up to 3months. MTX was released preferentially under mild hyperthermia
conditions. The multifunctional nanospheres were able to increase the
cytotoxicity of MTX towards Caco-2 and SW-480 colon cancer cells, in comparison
to free drug. Also, the nanospheres allowed the incorporated MTX to induce
greater cell cycle arrest and apoptotic effects than the free MTX. This study
provides evidences that MTX-SPIONs-PEG-PLA nanospheres are a promising solution
to address colorectal cancer over-expressing folate receptors, by a combinatory
approach.
PMID- 28415434
TI - Design and development of a hybrid bioartificial water-induced shape memory
polymeric material as an integral component for the anastomosis of human hollow
organs.
AB - A large number of pathologies require the resection of the bowel and anastomoses
to rejoin the two remaining stumps to regain lumen patency. Various materials
have been used to rejoin one bowel end to the other such as catgut, stainless
steel, and absorbable sutures. The present method for anastomosis surgery uses an
entero-entero anastomosis (EEA) circular stapler with only a staple line. This
method can have some drawbacks, such as intracellular fluid leakage and local
inflammations. The aim of this study is to design and develop a novel
bioartificial polymer with a ring shape made of polyvinyl alcohol (PVA) and
gelatin (80/20 ratio (w/w)) loaded both directly with acetylsalicylic acid and
with nanoparticles incorporating the same drug to reduce local inflammation even
for a prolonged period of time. A physical method (8cycles freezing/thawing) was
used to obtain a crosslinked bioartificial shape memory ring. Mechanical analysis
showed a storage modulus having a comparable value with that of the human colon.
HPLC analysis pointed out a sustained and prolonged release of the anti
inflammatory drug both immediately after anastomosis surgery and during healing
period. Cell culture tests indicated the cytocompatibility of the bioartificial
device. A shape memory of the hydrogel prepared in ring form was observed at 37
degrees C after immersion in water. These bioartificial devices can represent a
new approach to serve as a multifunctional anastomotic ring.
PMID- 28415435
TI - Developing an electrochemical sensor based on a carbon paste electrode modified
with nano-composite of reduced graphene oxide and CuFe2O4 nanoparticles for
determination of hydrogen peroxide.
AB - In this paper, a highly sensitive voltammetric sensor based on a carbon paste
electrode with CuFe2O4 nanoparticle (RGO/CuFe2O4/CPE) was designed for
determination of hydrogen peroxide (H2O2). The electrocatalytic reduction of H2O2
was examined using various techniques such as cyclic voltammetry (CV),
chronoamperometry, amperometry and differential pulse voltammetry (DPV). CuFe2O4
nanoparticles were synthesized by co-precipitation method and characterized with
scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray
diffraction (XRD), and Fourier transform infrared (FTIR) techniques. Then, a high
conductive platform based on a carbon paste electrode modified with RGO and
CuFe2O4 nanoparticles was prepared as a suitable platform for determination of
hydrogen peroxide. Under the optimum conditions (pH5), the modified electrode
indicated a fast amperometric response of <2s, good linear range of 2 to 200MUM,
low detection limit of 0.52MUM for determination of hydrogen peroxide. Also, the
peak current of differential pulse voltammetry (DPV) of hydrogen peroxide is
increased linearly with its concentration in the ranges of 2 to 10MUM and 10 to
1000MUM. The obtained detection limit for hydrogen peroxide was evaluated to be
0.064MUM by DPV. The designed sensor was successfully applied for the assay of
hydrogen peroxide in biological and pharmaceutical samples such as milk, green
tea, and hair dye cream and mouthwash solution.
PMID- 28415436
TI - A novel composite hydrogel initiated by Spinacia oleracea L. extract on Hela
cells for localized photodynamic therapy.
AB - In this study, the poly (ethylene glycol) double acrylates (PEGDA) was first
initiated by Spinacia oleracea L. extract (SOLE) to in situ form a polymer
hydrogel shell on Hela cells with near infra-red irradiation. The SOLE was also a
natural photosensitizer for photodynamic therapy of tumor. The use of SOLE is
simple, eco-friendly, low cost, and convenient. More importantly, the PEGDA/SOLE
composite hydrogel shell on Hela cells not merely prevents SOLE from diffusing to
normal tissue for reducing the side effects, but also keeps high SOLE
concentration on tumor cell for improving the antitumor effect. Such a hydrogel
system has good biocompatibility and exhibits high therapeutic efficacy. This
study extended the application of the SOLE/PEGDA gel in photodynamic therapy.
PMID- 28415437
TI - A simplistic approach to green future with eco-friendly luminescent carbon dots
and their application to fluorescent nano-sensor 'turn-off' probe for selective
sensing of copper ions.
AB - Zero-dimensional fluorescent nanoparticles having specificity as molecular probe
appears to be strategically balanced fluorescent nano-probes. In this work,
purified lemon extract and l-arginine have been thermally coupled for the
extremely acute detection of Cu2+ in aqueous medium. The Cu2+ ions may be
captured by the amino groups on the surface of the nano-sensor to form cupric
ammine complex resulting in quenched fluorescence via an inner filter effect. Our
proposed nano-probe is N-doped carbon dots (NCDs) which are efficiently selective
as fluorescent chemosensor due to enormous binding affinity towards Cu2+ in a
wide range of concentration (0.05-300MUM) within a few minutes.
PMID- 28415438
TI - Development of high efficacy peptide coated iron oxide nanoparticles encapsulated
amphotericin B drug delivery system against visceral leishmaniasis.
AB - Visceral leishmaniasis, a protozoan disease transmitted by phlebotomine sandflies
which affect mostly in Indian sub-continent. The treatment for visceral
leishmaniasis (VL) caused by Leishmania donovani are limited and unsatisfactory.
Currently available drug against such as miltefosine and polymer based drugs
amBisome has high efficacy against VL but found serious side effects and poor
absorbance. To overcome this, we developed peptide (glycine) coated iron oxide
(Fe3O4) nanoparticles (GINPs) encapsulated amphoterecin B (AmB) drug against
visceral leishmaniasis. Synthesis of GINPs was carried out and different
characterization technique used to confirm the synthesis and size of GINPs GINPs
AmB showed that particle size in the range of 10-15nm and closed to spherical in
shaped. GINPs-AmB showed release rate of AmB is higher at lower pH. Significantly
two fold higher efficacies of GINP encapsulated AmB during in vitro study. There
was a substantial reduction in the total parasite burden in spleen in treated
groups (GINPs encapsulate AmB), compare to AmB alone. The results obtained from
this study revealed that AmB loaded GINPs is twofold effective than AmB and
therefore, it opens a new avenue for use of AmB loaded GINPs against VL.
PMID- 28415439
TI - Novel synthesis and structural analysis of zinc oxide nanoparticles for the non
enzymatic glucose biosensor.
AB - A non-enzymatic glucose biosensor was developed by utilizing the zinc oxide
nanoparticles (ZnO NPs) synthesized by a novel green method using the leaf
extract of Ocimum tenuiflorum. The structural, optical and morphological
properties of ZnO NPs characterized by means of X-ray diffraction (XRD),
ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FTIR)
spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDAX)
spectroscopy, and transmission electron microscopy (TEM). The XRD analysis
revealed that the ZnO NPs were crystalline and had a hexagonal wurtzite
structure. The crystallite size measured by XRD was the same as that measured
using SEM and TEM. The UV-vis absorption spectrum estimates the band gap of ZnO
NPs present in the range of 2.82 to 3.45eV. The reduction and formation of ZnO
NPs mainly due to the involvement of leaf extract bio-molecular compounds
analyzed from the FTIR spectra. The SEM result confirms the morphology of the NPs
responsible from the various concentration of leaf extract in the synthesis
process. HRTEM analysis depicts the spherical structure of ZnO NPs. The
synthesized NPs have the average size ranges from 10 to 20nm. The fabricated
GCE/ZnO glucose sensor represents superior electro catalytic activity that has
been observed for ZnO NPs with a reproducible sensitivity of 631.30MUAmM-1cm-2,
correlation coefficient of R=0.998, linear dynamic range from 1-8.6mM, low
detection limit of 0.043MUM (S/N=3) and response time<4s.
PMID- 28415440
TI - Template electrodeposition of high-performance copper oxide nanosensors for
electrochemical analysis of hydrogen peroxide.
AB - We report on the facile electrodeposition of copper nanostructures on graphite
lead substrate using anionic, cationic and non-ionic surfactant templates.
Physical and electrochemical characterisation confirmed the influence of
templates on the morphology and electrochemical catalytic activities of the
copper electrodeposits. These electrodes were shown to be excellent
electrocatalyst for the fast detection of hydrogen peroxide. A maximum
sensitivity of 951.45MUA/mM/cm2, LOD of 0.43MUM, response time of <1s and a
linearity in wide range of concentration from 1MUM to 5mM were observed when
sodium dodecyl sulfate was used as the template. While most of the previously
reported sensors have advantages either on the facile synthesis or fast detection
of analyte, our methodology enables preparation of the electrode within 120s and
analysis within another 60s without any complicated procedure, thereby
demonstrating one of the fastest and cost-effective method for hydrogen peroxide
analysis with high sensitivity and selectivity.
PMID- 28415441
TI - Stress stiffened silicon nitride micro bridges array as substrate with tunable
stiffness for cell culture.
AB - Recently, interactions between one-dimensional structural stiffness of physical
micro environments and cell biological process have been widely studied. However
in previous studies, the influence of structural stiffness on biological process
was coupled with the influence of micro fiber curvature. Therefore decoupling the
influences of fiber curvature and structural stiffness on cell biological process
is of prime importance. In this study, we proposed a novel cell culture substrate
comprised of silicon nitride bridges whose structure stiffness can be regulated
by altering the axial residual stress without changing material and geometry
properties. Both theoretical calculations and finite element simulations were
performed to study the influence of residual stress on structure stiffness of
bridges. Then multi-positions AFM bending tests were implemented to measure local
stiffness of a single micro bridge so as to verify our predictions. NIH/3T3 mouse
fibroblast cells were cultured on our substrates to examine the feasibility of
the substrate application for investigating cellular response to microenvironment
with variable stiffness. The results showed that cells on the edge region near
bridge ends were more spread, elongated and better aligned along the bridge axial
direction than those on the bridge center region. The results suggest that cells
can sense and respond to the differences of stiffness and stiffness gradient
between the edge and the center region of the bridges, which makes this kind of
substrates can be applied in some biomedical fields, such as cell migration and
wound healing.
PMID- 28415442
TI - Small intestinal submucosa: A potential osteoconductive and osteoinductive
biomaterial for bone tissue engineering.
AB - SIS is an acellular, naturally occurring collagenous extracellular matrix (ECM)
material with various bioactive factors, which broadly applied in tissue
engineering in clinic. Several studies have applied SIS in bone tissue
engineering to enhance bone regeneration in animal models. However, the mechanism
was rarely investigated. The aim of the current study was to investigate the
osteoconductivity and osteoinductivity of SIS scaffold to bone regeneration
systematically and the potential mechanism. Our results showed that SIS scaffold
with excellent biocompatibility was beneficial for cell attachment,
proliferation, migration and osteogenic differentiation of various cells
contributing to bone repair. In mouse calvarial defect model, bone regeneration
was significantly enhanced in the defects implanted with SIS scaffolds, along
with the up-regulation of BMP-2 and CD31 expression. Accordingly, ID-1, the
downstream target gene of BMPs, was increased in BMSCs cultured on SIS scaffolds.
The results of this study suggest that SIS scaffold is a potential
osteoconductive and osteoinductive biomaterial which plays multiple roles to
various cells during process of bone regeneration.
PMID- 28415443
TI - 3-month parenteral PLGA microsphere formulations of risperidone: Fabrication,
characterization and neuropharmacological assessments.
AB - The study aims at formulation and characterization of three months parenteral
risperidone loaded polymeric microspheres (p-RLPMs) as a sustained delivery
system and established their in vitro and in vivo assessments. The p-RLPMs
formulations were prepared by solvent extraction and diffusion method. The
optimized p-RLPMs (batch RPLGA-1) formulation demonstrated favorable different
physicochemical properties such as mean particle size (104+/-5.34MUm), percent
porosity (44.56+/-3.11%) and percent drug loading (38.42+/-2.67%). The physical
state characterization, Fourier transformed infrared spectroscopy analysis showed
no changes in the chemical structure of risperidone (RPD) in the batch RPLGA-1
formulation and differential scanning calorimetry study confirmed, pure RPD
retained its crystallinity in the batch RPLGA-1 formulation. The SEM micrographs
of the all p-RLPMs formulations revealed the irregular shapes and indentations.
The GC/MS results showed that the residual organic solvent content in the batch
RPLGA-1 formulation was below the limits. Pharmacokinetic parameters revealed
that optimized RPLGA-1 formulation exhibited an initial burst followed by an
excellent sustained release as compared to pure RPD as well as other
formulations. Furthermore, in vivo studies of the batch, RPLGA-1 formulation
showed an antipsychotic effect that was significantly prolonged over that of pure
RPD solution for up to 72h with fewer extrapyramidal side effects. Thus, results
of this study prove the suitability of using poly(lactic-co-glycolic acid)
copolymer to develop sustained release p-RLPMs formulations that can tailor in
vivo behavior and enhance the pharmacological effectiveness of the RPD.
PMID- 28415444
TI - Formulation of thermoreversible gel of cranberry juice concentrate: Evaluation,
biocompatibility studies and its antimicrobial activity against periodontal
pathogens.
AB - The present work aims to investigate the efficacy of thermoreversible gel of
cranberry juice concentrate (CJC) as local drug delivery for the treatment of
periodontitis. CJC was initially tested for its antimicrobial activities like
MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of
organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P.
gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal
infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC
value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity
(70-85%). CJC was evaluated for its biocompatibility using periodontal
fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on
periodontopathogen PG derived virulence factors (fimA and kgp) was studied using
real time polymerase chain reaction (RT-PCR) technique wherein down regulation of
selected genes demonstrated inhibitory effect against PG virulence factors.
Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as
thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated
for its gelation temperature, viscosity, gel strength and mucoadhesive strength.
Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially
available chlorhexidine gluconate gel (0.2%) using agar well diffusion
demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the
formulated thermoreversible gel of CJC could serve as a novel herbal alternative
to currently available periodontal treatment modalities.
PMID- 28415445
TI - Microstructural and surface modifications and hydroxyapatite coating of Ti-6Al-4V
triply periodic minimal surface lattices fabricated by selective laser melting.
AB - Ti-6Al-4V Gyroid triply periodic minimal surface (TPMS) lattices were
manufactured by selective laser melting (SLM). The as-built Ti-6Al-4V lattices
exhibit an out-of-equilibrium microstructure with very fine alpha' martensitic
laths. When subjected to the heat treatment of 1050 degrees C for 4h followed by
furnace cooling, the lattices show a homogenous and equilibrium lamellar
alpha+beta microstructure with less dislocation and crystallographic defects
compared with the as-built alpha' martensite. The as-built lattices present very
rough strut surfaces bonded with plenty of partially melted metal particles. The
sand blasting nearly removed all the bonded metal particles, but created many
tiny cracks. The HCl etching eliminated these tiny cracks, and subsequent NaOH
etching resulted in many small and shallow micro-pits and develops a sodium
titanate hydrogel layer on the surfaces of the lattices. When soaked in simulated
body fluid (SBF), the Ti-6Al-4V TPMS lattices were covered with a compact and
homogeneous biomimetic hydroxyapatite (HA) layer. This work proposes a new method
for making Ti-6Al-4V TPMS lattices with a homogenous and equilibrium
microstructure and biomimetic HA coating, which show both tough and bioactive
characteristics and can be promising materials usable as bone substitutes.
PMID- 28415446
TI - Corrigendum to "Graphene oxide as a nanocarrier for controlled release and
targeted delivery of an anticancer active agent, chlorogenic acid" [J. Mater.
Sci. Eng. C 74(2017) 177-185].
PMID- 28415447
TI - Corrigendum to "Poly-dopamine-beta-cyclodextrin: A novel nanobiopolymer towards
sensing of amino acids at physiological pH" [Materials Science and Engineering: C
Volume 69, 1 December 2016, Pages 343-357].
PMID- 28415448
TI - Corrigendum to "Preparation and characterization of PEGylated multiwall carbon
nanotubes as covalently conjugated and non-covalent drug carrier: A comparative
study" [Mater. Sci. Eng. C 74 (2017)1-9].
PMID- 28415449
TI - Complementary approaches for the evaluation of biocompatibility of 90Y-labeled
superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles.
AB - Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and
therapeutic applications in medicine. Design and development of new iron oxide
based MNPs for such applications is of rather limited breadth without reliable
and sensitive methods to determine their levels in body tissues. Commonly used
methods, such as ICP, are quite problematic, due to the inability to decipher the
origin of the detected iron, i.e. whether it originates from the MNPs or
endogenous from tissues and bodily fluids. One of the approaches to overcome this
problem and to increase reliability of tracing MNPs is to partially substitute
iron ions in the MNPs with Er. Here, we report on the development of citric acid
coated (Fe,Er)3O4 nanoparticles and characterization of their physico-chemical
and biological properties by utilization of various complementary approaches. The
synthesized MNPs had a narrow (6-7nm) size distribution, as consistently seen in
atomic pair distribution function, transmission electron microscopy, and DC
magnetization measurements. The particles were found to be superparamagnetic,
with a pronounced maximum in measured zero-field cooled magnetization at around
90K. Reduction in saturation magnetization due to incorporation of 1.7% Er3+ into
the Fe3O4 matrix was clearly observed. From the biological standpoint, citric
acid coated (Fe,Er)3O4 NPs were found to induce low toxicity both in human cell
fibroblasts and in zebrafish (Danio rerio) embryos. Biodistribution pattern of
the MNPs after intravenous administration in healthy Wistar rats was followed by
the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found
in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID).
Quantitative agreement with these observations was obtained by ICP-MS elemental
analysis using Er as the detected tracer. Based on the favorable physical,
chemical and biological characteristics, citric acid coated (Fe,Er)3O4 MNPs could
be further considered for the potential application as a diagnostic and/or
therapeutic agent. This work also demonstrates that combined application of these
techniques is a promising tool for studies of pharmacokinetics of the new MNPs in
complex biological systems.
PMID- 28415450
TI - Impact of silica nanoparticle surface chemistry on protein corona formation and
consequential interactions with biological cells.
AB - Nanoparticles (NP) physico-chemical features greatly influence NP/cell
interactions. NP surface functionalization is often used to improve NP
biocompatibility or to enhance cellular uptake. But in biological media, the
formation of a protein corona adds a level of complexity. The aim of this study
was to investigate in vitro the influence of NP surface functionalization on
their cellular uptake and the biological response induced. 50nm fluorescent
silica NP were functionalized either with amine or carboxylic groups, in presence
or in absence of polyethylene glycol (PEG). NP were incubated with macrophages,
cellular uptake and cellular response were assessed in terms of cytotoxicity, pro
inflammatory response and oxidative stress. The NP protein corona was also
characterized by protein mass spectroscopy. Results showed that NP uptake was
enhanced in absence of PEG, while NP adsorption at the cell membrane was fostered
by an initial positively charged NP surface. NP toxicity was not correlated with
NP uptake. NP surface functionalization also influenced the formation of the
protein corona as the profile of protein binding differed among the NP types.
PMID- 28415451
TI - The sustained delivery of temozolomide from electrospun PCL-Diol-b-PU/gold
nanocompsite nanofibers to treat glioblastoma tumors.
AB - In the present study, the PCL-Diol-b-PU/Au nanocompsite nanofibers were
fabricated via electrospinning process during two different stages to load an
anticancer temozolomide (TMZ) drug into the nanofibers. The first stage was the
incorporation of Au nanoparticles into the nanofibers and the second stage was
coating the gold nanoparticles on the surface of PCL-Diol-b-PU/Au composite
nanofibers. The prepared nanofibrous formulations were characterized using FTIR,
SEM and TEM analysis. Box-Behnken-design was used to investigate the influence of
electrospinning parameters including solution concentration, applied voltage to
tip-collector distance ratio and collector speed on the morphology and fiber
diameter of PCL-Diol-b-PU/Au nanofibers. Drug loading efficiency, in vitro
release profiles of TMZ from PCL-Diol-b-PU/Au and gold-coated PCL-Diol-b-PU/Au
composite nanofibers as well as in vitro antitumor efficacy against U-87 MG human
glioblastoma cells were carried out. The TMZ release data were well described
using Korsmayer-Peppas kinetic model in which results indicated Fickian diffusion
of TMZ from nanofibers. The obtained results revealed the higher efficiency of
PCL-Diol-b-PU/Au@TMZ nanofibrous implants for treatment of glioblastoma tumors.
PMID- 28415452
TI - An ultra-sensitive Au nanoparticles functionalized DNA biosensor for
electrochemical sensing of mercury ions.
AB - The present work describes an effective strategy to fabricate a highly sensitive
and selective DNA-biosensor for the determination of mercury ions (Hg2+). The DNA
1 was modified onto the surface of Au electrode by the interaction between
sulfydryl group and Au electrode. DNA probe is complementary with DNA 1. In the
presence of Hg2+, the electrochemical signal increases owing to that Hg2+
mediated thymine bases induce the conformation of DNA probe to change from line
to hairpin and less DNA probes adsorb into DNA 1. Taking advantage of its
reduction property, methylene blue is considered as the signal indicating
molecule. For improving the sensitivity of the biosensor, Au nanoparticles (Au
NPs) modified reporter DNA 3 is used to adsorb DNA 1. Electrochemical behaviors
of the biosensor were evaluated by electrochemical impedance spectroscopy and
cyclic voltammetry. Several important parameters which could affect the property
of the biosensor were studied and optimized. Under the optimal conditions, the
biosensor exhibits wide linear range, high sensitivity and low detection limit.
Besides, it displays superior selectivity and excellent stability. The biosensor
was also applied for water sample detection with satisfactory result. The novel
strategy of fabricating biosensor provides a potential platform for fabricating a
variety of metal ions biosensors.
PMID- 28415453
TI - Role of generation on folic acid-modified poly(amidoamine) dendrimers for
targeted delivery of baicalin to cancer cells.
AB - Baicalin (BAI) has been reported to exert antitumor effects. However, BAI has
limited water solubility, non-specific tumor targeting, and low bioavailability,
which severely limited its clinical application. The aim of this study was to
develop folic acid (FA) covalently conjugated-polyamidoamine (PAMAM) dendrimers
(PAMAM-FA) as carrier systems for improvement of water solubility and tumor
specificity of BAI, and study the role of generation on the physiochemical
properties and biological effects of PAMAM-FA/BAI complexes. In this work, four
generations of PAMAM-FA were synthesized to entrap BAI. The average sizes of G3
FA/BAI, G4-FA/BAI, G5-FA/BAI, and G6-FA/BAI complexes were 174.4nm, 184.5nm,
258.8nm, and 247.5nm, respectively, and the zeta potentials of four PAMAM-FA/BAI
complexes were -2.9mV, -6.6mV, -9.3mV, -9.0mV, respectively. The entrapment
efficiencies of four PAMAM-FA/BAI complexes were 91.1%, 53.5%, 80.3%, and 91.9%,
respectively, and the drug loading of PAMAM-FA/BAI complexes were about 22%. The
formed PAMAM-FA/BAI complexes allowed sustained release of BAI in acidic PBS
(pH5.4). In cellular uptake assay, PAMAM-FA/BAI complexes demonstrated increased
drug uptake level in folate receptor (FR)-positive Hela cancer cells than FR
negative A549 cells, and the cellular uptake efficiency of PAMAM-FA is closely
related with the generation of PAMAM. The MTT assay results showed that PAMAM
FA/BAI complexes demonstrated enhanced toxicity against Hela cells than non-FA
modified PAMAM/BAI complexes, and the G6-FA/BAI demonstrated the best inhibition
efficiency. The cell cycle and cell apoptosis analysis further demonstrated the
tumor-specific therapeutic efficacy of PAMAM-FA/BAI. These results suggested that
the PAMAM-FA have the potential for targeted delivery of BAI into cancer cells to
enhance its anti-tumor efficacy.
PMID- 28415454
TI - Development of a DNA-liposome complex for gene delivery applications.
AB - The association structures formed by cationic liposomes and DNA (Deoxyribonucleic
acid)-liposome have been effectively utilized as gene carriers in transfection
assays. In this research study, cationic liposomes were prepared using a modified
lipid film hydration method consisting of a lyophilization step for gene delivery
applications. The obtained results demonstrated that the mean particle size had
no significant change while the polydispersity (PDI) increased after
lyophilization. The mean particle size slightly reduced after lyophilization
(520+/-12nm to 464+/-25nm) while the PDI increased after lyophilization (0.094+/
0.017 to 0.220+/-0.004). In addition. The mean particle size of vesicles
increases when DNA is incorporated to the liposomes (673+/-27nm). According to
the Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM)
images, the spherical shape of liposomes confirmed their successful preservation
and reconstitution from the powder. It was found that liposomal formulation has
enhanced transfection considerably compared to the naked DNA as negative control.
Finally, liposomal formulation in this research had a better function than
Lipofectamine(r) 2000 as a commercialized product because the cellular activity
(cellular protein) was higher in the prepared lipoplex than Lipofectamine(r)
2000.
PMID- 28415455
TI - Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin
hydrochloride.
AB - A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated
via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system
for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor
therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability,
blood compatibility and biocompatibility confirmed by the hemolytic test and in
vitro cytotoxicity study. Its safety issue was greatly improved via Hep
modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and
dependent on pH value. The release rate of DOX from GO-ADH-Hep/DOX was pH
sensitive and much-slower than that of free DOX solution suggesting the sustained
drug-release capacity of this prepared nanocomplexes. In addition, the results of
cytotoxicity study illustrated that this fabricated nanocomplexes displayed
effective cytotoxicity to MCF-7 and HepG2 cells. What's more, the results of the
in vivo pharmacokinetic study was also indicated that the GO-ADH-Hep/DOX
nanocomplexes could significantly prolong the retention time of DOX in vivo and
this was consistent with the in vitro drug release performance. And finally,
according to the biodistribution study, DOX delivered by GO-ADH-Hep could reduce
cardiotoxicity deriving from DOX solution and also decrease the pulmonary
toxicity deriving from unmodified GO. Based on the in vitro and in vivo
investigations, the fabricated GO-ADH-Hep could be a promising candidate as an
ideal nano-carrier for drug delivery and anti-cancer therapy.
PMID- 28415456
TI - Osteoinductive composite coatings for flexible intramedullary nails.
AB - This work presents composite coatings based on a copolymer of vinylidene fluoride
with tetrafluoroethylene (VDF-TeFE) and hydroxyapatite (HA) for flexible
intramedullary nails (FIN). The effect of the proportion of VDF-TeFE (100-25%
wt.) on physicochemical and biological properties of the composite coatings was
investigated. It was shown that a decrease of VDF-TeFE in the coating hinders its
crystallization in beta and gamma forms which have piezoelectric properties. The
decrease also reduces an adhesive strength to 9.9+/-2.4MPa and a relative
elongation to 5.9+/-1.2%, but results in increased osteogenesis. It was
demonstrated that the composite coatings with 35% VDF-TeFE has the required
combination of physicochemical properties and osteogenic activity. Comparative
studies of composite coatings (35% VDF-TeFE) and calcium phosphate coatings
produced using micro-arc oxidation, demonstrated comparable results for strength
of bonding of these FINs with trabecular bones (~530MPa). It was hypothesized
that the high osteoinductive properties of the composite coatings are due to
their piezoelectric properties.
PMID- 28415457
TI - A novel nano-hydroxyapatite - PMMA hybrid scaffolds adopted by conjugated thermal
induced phase separation (TIPS) and wet-chemical approach: Analysis of its
mechanical and biological properties.
AB - In this study, we report the preparation of nano-hydroxyapatite (nHAp)
incorporated poly(methyl methacrylate) (PMMA) scaffolds by conjugated thermal
induced phase separation (TIPS) and wet-chemical approach, which essentially
facilitates the enhancement of both mechanical as well as biological properties
of the scaffolds. The dissolution of PMMA was accomplished by acetone (Ace
scaffold), ethanol-water (E-W scaffold) and isopropanol-water (I-W scaffold)
mixtures as solvents. The existence of nHAp in PMMA matrix was investigated
systematically. The higher degree of porous architecture was achieved from Ace
scaffolds compared to both I-W and E-W scaffolds. On the other hand, the dense
porous architecture of the I-W scaffold exhibited superior hardness and
compressive strength than that of the Ace and E-W scaffolds. All the fabricated
samples demonstrated enhanced in vitro bioactivity with respect to increasing
immersion period as a result of flower-like in vitro apatite layer formation. The
MTT assay was carried out for 1day and 3day culture using Saos-2 osteoblast-like
cells, which showed better cell proliferation with increasing culture period
owing to the interconnected pore architecture of scaffolds and the rational
hemocompatibility as per the ASTM standard F756-00.
PMID- 28415458
TI - Nanopatterned polystyrene-b-poly(acrylic acid) surfaces to modulate cell-material
interaction.
AB - In this work we explore the effect of surface nanoarchitecture of polystyrene
(PS) and polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymer films on
cell viability. PS and PS-b-PAA have been nanopatterned at temperatures of 110,
120 and 140 degrees C using nanoporous aluminium oxide membranes (AAO) as a
template. Surface architecture strongly depends on the infiltration temperature
and the nature of the infiltrated polymer. High patterning temperatures yield
hollow fibre shape architecture at the nanoscale level, which substantially
modifies the surface hydrophobicity of the resulting materials. Up to date very
scarce reports could be found in the literature dealing with the interaction of
microstructured/nanostructured polymeric surfaces with cancer cells. Therefore,
MCF-7 breast cancer cells have been selected as a model to conduct cell viability
assays. The findings reveal that the fine-tuning of the surface nanoarchitecture
contributes to the modification of its biocompatibility. Overall, this study
highlights the potential of AAO membranes to obtain well-defined tailored
morphologies at nanoscale level and its importance to develop novel soft
functional surfaces to be used in the biomedical field.
PMID- 28415459
TI - The effect of hirudin modification of silk fibroin on cell growth and
antithrombogenicity.
AB - Thrombus formation remains a particular challenge for small-diameter vascular
grafts. In this study, the direct thrombin inhibitor hirudin (Hir) was used to
modify silk fibroin films in an attempt to enhance its antithrombogenic
properties. Hir was successfully attached to silk fibroin and uniformly
distributed in the regenerative material. Hir-modified films showed good
cytocompatibility, and supported adhesion and proliferation of fibroblasts
(L929), human umbilical vascular endothelial cells (HUVECs) and human aortic
smooth muscle cells (HASMCs). Proliferation of HAVSMCs was inhibited by
increasing Hir concentration. Activated partial thrombin time (APTT), prothrombin
time (PT) and thrombin time (TT) of Hir-modified silk fibroin tubular scaffolds
(SFTSs) were all increased markedly compared with fresh rabbit blood, ethanol
treated SFTS and unmodified SFTS, demonstrating the improved antithrombogenicity
of SFTSs following modification with Hir.
PMID- 28415460
TI - Poly arginine-graphene quantum dots as a biocompatible and non-toxic
nanocomposite: Layer-by-layer electrochemical preparation, characterization and
non-invasive malondialdehyde sensory application in exhaled breath condensate.
AB - This study reports on the electropolymerization of a low toxic and biocompatible
polymer with entitle poly arginine-graphene quantum dots (PARG-GQDs) as a novel
strategy for surface modification of glassy carbon (GC) surface and preparation a
new interface for biomedical application. The fabrication of PARG-GQDs on GCE was
performed using Layer-by-layer regime. Scanning electron microscopy (SEM) was
confirmed dispersion of GQDs on the surface of PARG which lead to increase of
surface coverage of PARG. The redox behavior of prepared sensor was then
characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV)
and chronoamperometry (CHA), square wave voltammetry (SWV), linear sweep
voltammetry (LSV). The electroactivity of PARG-GQDs coating towards detection and
determination of malondialdehyde (MDA) as one of the most common biomarkers of
oxidative stress, was then studied. Then, application of prepared sensor for the
detection of MDA in exhaled breath condensate (EBC) is described. Electrochemical
based sensor shows the lower limit of quantification (LLOQ) were 0.329nanomolar.
This work is the first report on the integration of GQDs to poly amino acids.
Further development can lead to monitoring of MDA or other exhaled breath
biomarkers by GQDs functionalized poly amino acids in EBC using electrochemical
methods.
PMID- 28415461
TI - A new bioavailability enhancement strategy of curcumin via self-assembly nano
complexation of curcumin and bovine serum albumin.
AB - Amorphous drug nanoparticles have recently emerged as a superior bioavailability
enhancement strategy for poorly soluble drugs in comparison to the conventional
microscale amorphous solid dispersions. In particular, amorphous drug
nanoparticle complex (or nanoplex) represents an attractive bioavailability
enhancement strategy of curcumin (CUR) - a medicinal herb known for its wide
ranging therapeutic activities - attributed to the high payload, cost-effective
preparation, and supersaturation generation of the nanoplex. To address the poor
colloidal stability of conventional nanoplex formulations, we herein developed a
new class of CUR nanoplex by complexation of CUR with bovine serum albumin (BSA).
The effects of two key variables in drug-protein complexation, i.e. pH and mixing
ratio (MBSA/CUR), on the physical characteristics and preparation efficiency were
investigated. While the CUR-BSA nanoplex preparation was found to favor acidic pH
and MBSA/CUR below unity, the nanoplex's physical characteristics were minimally
affected by pH and MBSA/CUR. At the optimal condition, CUR-BSA nanoplex with size
~90nm, zeta potential ~27mV, and payload ~70% were produced at nearly 100% CUR
utilization rate and ~80% yield. The nanoplex produced a prolonged
supersaturation level at ~9* of the saturation solubility for 4h. The dissolution
rate could be modulated by thermal treatment of the nanoplex post its
preparation. The long-term amorphous state stability, storage colloidal
stability, and preserved bioactivity of the nanoplex were successfully
established. Lastly, the CUR-BSA nanoplex was found to be superior to the
conventional nanoplex in its size, supersaturation generation, colloidal
stability, and yield.
PMID- 28415462
TI - Microencapsulation of eugenol molecules by beta-cyclodextrine as a thermal
protection method of antibacterial action.
AB - Eugenol is natural oil that has excellent antibacterial properties but cannot be
used to fabricate many products that require thermal processing. One possible
alternative to the use of the eugenol molecules in high-temperature processes is
the encapsulation of these molecules in a structure that is not toxic and is
resistant to thermal treatment. This work investigated the encapsulation process
of eugenol molecules in beta-cyclodextrine and the antibacterial properties of
eugenol-beta-cyclodextrine (the eugenol-betaCD complex) against Escherichia coli
and Staphylococcus aureus. The FTIR, DSC, MEV and TGA results show that the
encapsulation method is an excellent alternative to increase the thermal
stability of eugenol molecules. A value of 241.32L.mol-1 was determined for the
formation constant (Kc) of the eugenol-betaCD complex, which confirmed the
success of the encapsulation process. The MEV analysis shows the formation of
approximately 12MUm microcapsules. After the thermal treatment of the eugenol
betaCD complex at a temperature of 80 degrees C for 2h, the complex retained
significant antibacterial action, which confirms the thermal protection of the
eugenol molecules. The minimum inhibitory concentration (MIC) and agar diffusion
results show that the microcapsules containing 17.08mmol.L-1 of eugenol exhibited
excellent antibacterial action against Escherichia coli and Staphylococcus aureus
after thermal treatment.
PMID- 28415463
TI - In vitro characterisation of a sol-gel derived in situ silica-coated silicate and
carbonate co-doped hydroxyapatite nanopowder for bone grafting.
AB - Design and synthesis of materials with better properties and performance are
essential requirements in the field of biomaterials science that would directly
improve patient quality of life. For this purpose, in situ silica-coated silicate
and carbonate co-doped hydroxyapatite (Sc/S.C.HA) nanopowder was synthesized via
the sol-gel method. Characterisation of the prepared nanopowder was carried out
by XRD, FTIR, TEM, SEM, EDX, ICP, zeta potential, acid dissolution test, and cell
culture test. The substitution of the silicate and carbonate ions into
hydroxyapatite structure was confirmed by FTIR analysis. XRD analysis showed that
silica is an amorphous phase, which played a role in covering the surface of the
S.C.HA nanoparticles as confirmed by acid dissolution test. Low thickness and low
integrity of the amorphous silica surface layer facilitated ions release from
S.C.HA nanoparticles into physiological saline solution. Zeta potential of the
prepared nanopowder suspended in physiological saline solution was -27.3+/-0.2mV
at pH7.4. This negatively charged surface, due to the presence of amorphous
silica layer upon the S.C.HA nanoparticles, not only had an accelerating effect
on in vitro biomineralization of apatite, but also had a positive effect on cell
attachment.
PMID- 28415464
TI - In situ forming chitosan hydrogels: Preliminary evaluation of the in vivo
inflammatory response.
AB - This study aims to provide important preliminary in vivo data on the general
biocompatibility and degradation of in situ forming chitosan hydrogels which
differ in the type of cross-linking: physical cross-linking (with glycerol
phosphate disodium salt) and physico/chemical co-cross-linking (with glycerol
phosphate disodium salt and genipin). Additionally, in vitro degradation studies,
using lysozyme, were conducted for comparison. The subcutaneous implantation of
the liquid formulations of both hydrogels in animal model (Wistar rats) was
performed to assess tissue response at the end of two time periods (8 and
30days). Although the properties of both hydrogels are different (namely, pore
size and mechanical strength), leading to remarkably distinct in vitro
degradation behaviors, the in vivo degradation is quite similar for both types.
Regarding biocompatibility, the in vivo evaluation performed by histological
analysis, showed a mild to moderate chronic inflammatory reaction with no foreign
body reaction, demonstrating that both hydrogels show good results for in vivo
biodegradation and biocompatibility, therefore are most adequate for biomedical
applications.
PMID- 28415465
TI - Photochemical coating of Kapton(r) with hydrophilic polymers for the improvement
of neural implants.
AB - The polyimide Kapton(r) was coated photochemically with hydrophilic polymers to
prevent undesirable cell growth on the polyimide surface. The polymer coatings
were generated using photochemically reactive polymers synthesized by a simple
and modular strategy. Suitable polymers or previously synthesized copolymer
precursors were functionalized with photoactive arylazide groups by a polymer
analogous amide coupling reaction with 4-azidobenzoic acid. A photoactive
chitosan derivative (chitosan-Az) and photochemically reactive copolymers
containing DMAA, DEAA or MTA as primary monomers were synthesized using this
method. The amount of arylazide groups in the polymers was adjusted to
approximately 5%, 10% and 20%. As coating on Kapton(r) all polymers effect a
significantly reduced water contact angle (WCA) and consequently a rise of the
surface hydrophilicity compared to the untreated Kapton(r). The presence of the
polymer coatings was also proven by ATR-IR spectroscopy. Coatings with chitosan
Az and the DEAA copolymer cause a distinct inhibition of the growth of
fibroblasts. In the case of the DMAA copolymer even a strong anti-adhesive
behavior towards fibroblasts was verified. Biocompatibility of the polymer
coatings was proven which enables their utilization in biomedical applications.
PMID- 28415466
TI - Effect of lubricant on the reliability of dental implant abutment screw joint: An
in vitro laboratory and three-dimension finite element analysis.
AB - Biomechanical factors play a key role in the success of dental implants. Fracture
and loosening of abutment screws are major issues. This study investigated the
effect of lubricants on the stability of dental implant-abutment connection. As
lubricants, graphite and vaseline were coated on the abutment screw surface,
respectively, and a blank without lubricant served as the control. The total
friction coefficient (MUtot), clamping force, fatigue behavior and detorque of
the joint combined with dynamic cyclic loading were measured under different
lubricating conditions. Further, a three-dimensional finite element analysis was
used to investigate stress distribution, in conjunction with experimental images.
The results showed that the lubricant reduced MUtot, which in turn led to an
increase in clamping force. Decrease in loading increased the fatigue life of the
screw. However, use of lubricant at high load reduced the fatigue life. Ductile
fracture at the first thread of the screw was the chief failure mode, which was
due to maximum von Mises stress. Higher stress levels occurred in the lubricant
groups. Lubricated screws resulted in lower detorque which made the joint easier
to loosen. In conclusion, the lubricant cannot effectively improve the
reliability of dental implant-abutment connection. Keeping the interfaces of
implant-screw uncontaminated and strengthening the surface of the screw may be
recommend for clinical operation and future design.
PMID- 28415467
TI - Poly(l-lactic acid) and polyurethane nanofibers fabricated by solution blow
spinning as potential substrates for cardiac cell culture.
AB - This paper presents a comparison and evaluation of cardiac cell proliferation on
poly(l-lactic acid) (PLLA) and polyurethane (PU) nanofibrous mats fabricated by
solution blow spinning (SBS). Three different cardiac cell lines: rat
cardiomyoblasts (H9C2 line), human (HCM) and rat cardiomyocytes (RCM) were used
for experiments. Cell morphology, orientation and proliferation were investigated
on non-modified and protein-modified (fibronectin, collagen, gelatin, laminin,
poly-l-lysine) surfaces of both types of nanofibers. Obtained results of cell
culture on nanofibers surfaces were compared to the results of cell culture on
polystyrene (PS) surfaces modified in the same way. The results indicated that in
most cases polymeric nanofibers (PLLA and PU) are better substrates for cardiac
cell culture than PS surfaces. All types of investigated cells, cultured on
nanofibers (PLLA and PU), had more elongated shape than cells cultured on PS
surfaces. Moreover, cells were arranged in parallel to each other, according to
fibers orientation. Additionally, it was shown that the protein modifications of
investigated surfaces influenced on cell proliferation. Therefore, we suggest
that the cardiac cell culture on nanofibrous mats fabricated by SBS could be more
advanced experimental in vitro model for studies on the effect of various cardiac
drugs than traditional culture on PS surface.
PMID- 28415468
TI - Characterization of the surface physico-chemistry of plasticized PVC used in
blood bag and infusion tubing.
AB - Commercial infusion tubing and blood storage devices (tubing, blood and platelets
bags) made of plasticized PVC were analyzed by spectroscopic, chromatographic and
microscopic techniques in order to identify and quantify the additives added to
the polymer (lubricants, thermal stabilizers, plasticizers) and to put into
evidence their blooming onto the surface of the devices. For all the samples,
deposits were observed on the surface but with different kinds of morphologies.
Ethylene bis amide lubricant and metallic stearate stabilizers were implicated in
the formation of these layers. In contact with aqueous media, these insoluble
deposits were damaged, suggesting a possible particulate contamination of the
infused solutions.
PMID- 28415469
TI - Pore structures and mechanical properties of porous titanium scaffolds by
bidirectional freeze casting.
AB - Porous titanium scaffolds with long-range lamellar structure were fabricated
using a novel bidirectional freeze casting method. Compared with the ordinarily
porous titanium materials made by traditional freeze casting, the titanium walls
can offer the structure of ordered arrays with parallel to each other in the
transverse cross-sections. And titanium scaffolds with different pore width, wall
size and porosity can be synthesized in terms of adjusting the fabrication
parameters. As the titanium content was increased from 15vol.% to 25vol.%, the
porosity and pore width decreased from 67+/-3% to 50+/-2% and 80+/-10MUm to 67+/
7MUm, respectively. On the contrary, as the wall size was increased from 18+/
2MUm to 30+/-3MUm, the compressive strength and stiffness were increased from
58+/-8MPa to 162+/-10MPa and from 2.5+/-0.7GPa to 6.5+/-0.9GPa, respectively. The
porous titanium scaffolds with long-range lamellar structure and controllable
pore structure produced in present work will be capable of having potential
application as bone tissue scaffold materials.
PMID- 28415470
TI - Spatial stress distribution analysis by thermoelastic stress measurement and
evaluation of effect of stress concentration on durability of various orthopedic
implant devices.
AB - Toward the development of highly durable devices, we investigated the effect of
the thermoelastic constants of implantable raw metals and the surface stress
distribution on the durability of various types of implant device by
thermoelastic stress measurement and by evaluating the effect of the stress
concentration. Surface stress was dynamically calculated from the bending moment,
and the modulus of a section of a device was found to be consistent with the
surface stress obtained by thermoelastic stress measurement. The durability
limits of various types of bone plate and compression hip screw (CHS) calculated
from maximum load vs number of cycles data (L-N data) were close to the notch
fatigue strength of the raw material. The concentration factor of an artificial
hip stem surface was estimated by comparing the L-N data of the stem and the S-N
curve of the raw material. The dynamic analysis of durability by thermoelastic
stress measurement is useful for selecting the worst case (a product
deteriorating to the most severe state) in medical device design.
PMID- 28415471
TI - Synthesis and characterization of Ti-27.5Nb alloy made by CLAD(r) additive
manufacturing process for biomedical applications.
AB - Biocompatible beta-titanium alloys such as Ti-27.5(at.%)Nb are good candidates
for implantology and arthroplasty applications as their particular mechanical
properties, including low Young's modulus, could significantly reduce the stress
shielding phenomenon usually occurring after surgery. The CLAD(r) process is a
powder blown additive manufacturing process that allows the manufacture of
patient specific (i.e. custom) implants. Thus, the use of Ti-27.5(at.%)Nb alloy
formed by CLAD(r) process for biomedical applications as a mean to increase
cytocompatibility and mechanical biocompatibility was investigated in this study.
The microstructural properties of the CLAD-deposited alloy were studied with
optical microscopy and electron back-scattered diffraction (EBSD) analysis. The
conservation of the mechanical properties of the Ti-27.5Nb material after the
transformation steps (ingot-powder atomisation-CLAD) were verified with tensile
tests and appear to remain close to those of reference material.
Cytocompatibility of the material and subsequent cell viability tests showed that
no cytotoxic elements are released in the medium and that viable cells
proliferated well.
PMID- 28415472
TI - Supercritical carbon dioxide extracted extracellular matrix material from adipose
tissue.
AB - Adipose tissue is a rich source of extracellular matrix (ECM) material that can
be isolated by delipidating and decellularizing the tissue. However, the current
delipidation and decellularization methods either involve tedious and lengthy
processes or require toxic chemicals, which may result in the elimination of
vital proteins and growth factors found in the ECM. Hence, an alternative
delipidation and decellularization method for adipose tissue was developed using
supercritical carbon dioxide (SC-CO2) that eliminates the need of any harsh
chemicals and also reduces the amount of processing time required. The resultant
SC-CO2-treated ECM material showed an absence of nuclear content but the
preservation of key proteins such as collagen Type I, collagen Type III, collagen
Type IV, elastin, fibronectin and laminin. In addition, other biological factors
such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast
growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also
retained. Subsequently, the resulting SC-CO2-treated ECM material was used as a
bioactive coating on tissue culture plastic (TCP). Four different cell types
including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical
vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells
and human monocytic leukemia cells (THP-1) were used in this study to show that
the SC-CO2-treated ECM coating can be potentially used for various biomedical
applications. The SC-CO2-treated ECM material showed improved cell-material
interactions for all cell types tested. In addition, in vitro scratch wound assay
using HaCaT cells showed that the presence of SC-CO2-treated ECM material
enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1
derived macrophages showed that the SC-CO2-treated ECM material did not evoke pro
inflammatory responses from the THP-1-derived macrophages. Overall, this study
shows the efficacy of SC-CO2 method for delipidation and decellularization of
adipose tissue whilst retaining its ECM and its subsequent utilization as a
bioactive surface coating material for soft tissue engineering, angiogenesis and
wound healing applications.
PMID- 28415473
TI - Preparation of a novel bioavailable curcuminoid formulation (CureitTM) using
Polar-Nonpolar-Sandwich (PNS) technology and its characterization and
applications.
AB - Health benefits of curcuminoid are highly limited due to their poor aqueous
solubility, very low systemic bioavailability, fast metabolic alterations and
rapid elimination. In this study, a novel bioavailable curcuminoid formulation
CureitTM was prepared by using Polar-Nonpolar-Sandwich (PNS) technology with
complete natural turmeric matrix (CNTM). The synthesized bioavailable curcuminoid
formulation CureitTM was characterizations by Nuclear magnetic resonance
spectroscopy (NMR), scanning electron microscopy (SEM), X-ray diffraction (XRD),
Fourier transform infra-red (IR), current-voltage (I-V) study, Quadrupole Time-of
Flight Mass Spectrometry (Q-TOF), differential scanning calorimeter (DSC) and
thermogravimetric analysis (TGA). NMR study showed the presence of hydrogen
bonding interactions with curcuminoids, polar and non-polar compounds in the PNS
technology. SEM images indicated that CureitTM was almost spherical and well
dispersed with rough morphology, and separated with three layers of PNS
formulation. The chemical profile of CureitTM was analyzed by Q-TOF confirmed the
presence of curcuminoids (curcumin, demethoxycurcumin and bismethoxycurcumin),
lactones, sesquiterpenes and their derivatives derived from polar layer, aromatic
turmerone, dihydroturmerone, turmeronol, curdione and bisacurone derived from non
polar layer. IR, XRD, DSC and TGA also confirmed the presence of curcuminoids
with high stability in the PNS formulation. Various biological activities of
CureitTM were also discussed.
PMID- 28415474
TI - Palladium nanoparticles in electrochemical sensing of trace terazosin in human
serum and pharmaceutical preparations.
AB - In this approach, palladium nanoparticle film was simply fabricated on the
surface of carbon paste electrode by electrochemical deposition method. The film
was characterized using scanning electron microscopy, electrochemical impedance
spectroscopy and cyclic voltammetry. The prepared electrode exhibited an
excellent electrocatalytic activity toward detection of trace amounts of
terazosin, which is an antihypertensive drug. Under the optimum experimental
conditions, a linear range of 1.0*10-8-1.0*10-3molL-1 with a detection limit of
1.9*10-9molL-1 was obtained for determination of terazosin using differential
pulse voltammetry as a sensitive method. The efficiency of palladium nanoparticle
film on the surface of carbon paste electrode successfully proved for
determination of terazosin in pharmaceutical sample and human serum sample with
promising recovery results. The effect of some foreign species has been studied.
PMID- 28415475
TI - Novel non-cytotoxic, bioactive and biodegradable hybrid materials based on
polyurethanes/TiO2 for biomedical applications.
AB - Titanium compounds have demonstrated great interfacial properties with biological
tissues whereas a wide variety of polyurethanes have also been successfully
probed in medical applications. However, studies about hybrids based on
polyurethanes/TiO2 for medical applications are scarce. The aim of this work is
to design novel biodegradable hybrid materials based on polyurethanes/TiO2 (80%
organic-20% inorganic) and to perform a preliminary study of the potential
applications in bone regeneration. The hybrids have been prepared by a sol-gel
reaction using titanium isopropoxide as precursor of the inorganic component and
polyurethane as the organic one. A series of polyurethanes has been prepared
using different polyesters glycol succinate as soft segment, and 1,6
diisocyanatohexane (HDI) and butanediol (BD) as linear hard segment. The
spectroscopy techniques used allow to confirm the formation of the required
polyurethanes by the identification of bands related to carboxylic groups (COOH),
and the amine groups (NH), and also the TiOH bonds and the bonds related to the
interconnected network between the inorganic and the organic components from
hybrids. The results from SEM/EDS show a homogeneous distribution of the
inorganic component into the organic matrix. The nontoxic character of the hybrid
(H400) was probed using MG-63 cell line with over 90% of cell viability. Finally,
the formation of a hydroxyapatite layer in the material surface after 21days of
soaking in SBF shows the bioactive character.
PMID- 28415476
TI - Cellular compatibility of nanocomposite scaffolds based on hydroxyapatite
entrapped in cellulose network for bone repair.
AB - In the past few decades, artificial graft materials for bone tissue engineering
have gained much importance. In this study, novel porous 3D nanocomposite
scaffolds composed of polyacrylamide grafted cellulose and hydroxyapatite were
proposed. They were characterized using scanning electron microscopy (SEM),
Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray
spectroscopy (EDX), and X-ray diffraction analysis (XRD). The swelling behavior
of the scaffolds was examined in both water and phosphate buffer saline (PBS)
solution. The cytotoxicity of the scaffolds was determined by MTT assays on human
fibroblast gum (HuGu) cells. Results showed that the nanocomposite scaffolds were
highly porous with maximum porosity of 85.7% interconnected with a pore size of
around 72-125MUm. The results of cell culture experiments showed that the
scaffolds extracts do not have cytotoxicity in any concentration. Obtained
results suggested that the introduced scaffolds are comparable with the
trabecular bone from the compositional, structural, and mechanical perspectives
and have a great potential as a bone substitute.
PMID- 28415477
TI - Studies on l-histidine capped Ag and Au nanoparticles for dopamine detection.
AB - This work demonstrates the effective surface functionalization of Ag, Au and
bimetallic Ag-Au nanoparticles using l-histidine for colorimetric detection of
dopamine (DA) which plays majorly in recognizing the neurological disorder. l
Histidine (l-His) capped Ag, Au, and bimetallic Ag-Au nanoparticles are
characterized using physico-chemical techniques. The optical behaviour of
nanoparticles has been analysed at various time intervals using UV-Vis absorption
spectroscopy. FT-IR results provide the evidence of chemical bonding between l
histidine and metal nanoparticles. Its structure with the capping of l-His was
clearly shown in HR-TEM images. The average size of nanoparticles has calculated
from TEM image fringes are 11nm, 5nm and 6.5nm respectively, matches with
crystals size calculated from X-ray diffraction pattern. Enhanced optical nature
of nanoparticles provides the best platform to develop a colorimetric-based
biosensor for DA detection. After addition of DA, a rapid colour change has been
noted in colloids of nanoparticles. The substantial changes in absorbance and
lambdamax in metal nanoparticles respect to DA concentration have been observed
and formulated. This is one of the successive methods for trace level
determination of DA and will be going to a significant material for designing
biosensor to determine DA in real extracellular body fluids.
PMID- 28415478
TI - Comparison of unusual carbon-based working electrodes for
electrochemiluminescence sensors.
AB - In this work, unconventional carbon-based materials were investigated for use in
electrochemiluminescence (ECL) working electrodes. Precursors such as bamboo,
pistachio shells, kevlar(r) fibers and camphor were differently treated and used
as working electrodes in ECL experiments. After a proper process they were
assembled as electrodes and tested in an electrochemical cell. Comparison among
them and with a commercial glassy carbon electrode (GCE) shows a very good
response for all of them thus demonstrating their potential use as disposable low
cost electrodes for early detection electrochemical analysis.
PMID- 28415479
TI - Natural polymeric microspheres for modulated drug delivery.
AB - Microspheres can be regarded as a suitable platform for the development of ad hoc
drug delivery systems, since the targeted release of a therapeutic agent can
effectively contribute to support and improve a pharmacological protocol.
However, several crucial factors related to the selection of materials, drugs and
fabrication techniques should be critically analyzed in order to enhance the
expected performance. Dealing with highly compatible materials, e.g. naturally
derived polymers and "green" reagents, can be a valid approach. For this aim,
gelatin, chitosan and blend microspheres were produced by emulsion technique
simply using distilled water and olive oil. Necessarily, due to the intrinsic
instability of the selected materials in aqueous environment, microspheres were
cross-linked with genipin, an extremely low cytotoxic agent, at three different
concentration (i.e., 0.1, 0.5, 1% w/v). Collected microspheres were then loaded
with methylene blue (MB), as drug model. Morphological analysis revealed
homogeneous microspheres characterized by an average diameter comprised in the
range 42-54MUm. In vitro MB temporal delivery was assessed until complete
release, which occurred in about 3days for gelatin and 30days for chitosan
microspheres. Nanoindentation analysis was performed to evaluate how polymers and
genipin influenced the mechanical properties of microspheres. Finally, the effect
of released MB was investigated by means of chicken embryo chorioallantoic
membrane assay, highlighting anti-angiogenic properties for gelatin differently
from chitosan and blend microspheres.
PMID- 28415480
TI - Improvement of mechanical and biological properties of Polycaprolactone loaded
with Hydroxyapatite and Halloysite nanotubes.
AB - Hydroxyapatite (HA) and Halloysite nanotubes (HNTs) percentages have been
optimized in Polycaprolactone (PCL) polymeric matrices to improve mechanical,
thermal and biological properties of the composites, thus, to be applied in bone
tissue engineering or as fixation plates. Addition of HA guarantees a proper
compatibility with human bone due to its osteoconductive and osteoinductive
properties, facilitating bone regeneration in tissue engineering applications.
Addition of HNTs ensures the presence of tubular structures for subsequent drug
loading in their lumen, of molecules such as curcumin, acting as controlled drug
delivery systems. The addition of 20% of HA and different amounts of HNTs leads
to a substantial improvement in mechanical properties with values of flexural
strength up to 40% over raw PCL, with an increase in degradation temperature. DMA
analyses showed stability in mechanical and thermal properties, having as a
result a potential composite to be used as tissue engineering scaffold or
resorbable fixation plate.
PMID- 28415481
TI - Modeling of drug release behavior of pH and temperature sensitive poly(NIPAAm-co
AAc) IPN hydrogels using response surface methodology and artificial neural
networks.
AB - An interpenetrated polymer network (IPN) poly(NIPAAm-co-AAc) hydrogel was
synthesized by two polymerization method: emulsion and solution polymerization.
The pH- and temperature-sensitive hydrogel was loaded by swelling with riboflavin
drug, a B2 vitamin. The release of riboflavin as a function of time has been
achieved under different pH and temperature environments. The determination of
experimental conditions and the analysis of drug delivery results were achieved
using response surface methodology (RSM). In this work, artificial neural
networks (ANNs) in MATLAB were also used to model the release data. The
predictions from the ANN model, which associated input variables, produced
results showing good agreement with experimental data compared to the RSM
results.
PMID- 28415482
TI - Terminal sterilization of equine-derived decellularized tendons for clinical use.
AB - In the last few years, the demand for tissue substitutes has increased and
decellularized matrices has been widely proposed in the medical field to restore
severe damages thanks to high biocompatibility and biomechanical properties
similar to the native tissues. However, biological grafts represent a potential
source of contamination and disease transmission; thus, there is the need to
achieve acceptable levels of sterility. Several sterilization methods have been
investigated with no consensus on the outcomes in terms of minimizing structural
damages and preserving functional features of the decellularized matrix for
transplantation in humans. With the aim of making decellularized tendons safe for
clinical use, we evaluated the cytocompatibility, and biochemical, structural and
biomechanical variations of decellularized equine tendons sterilized with
peracetic acid or beta-irradiation and differently wet- or dry- stored at 4
degrees C or -80 degrees C, respectively. Considering that both sterilization and
long-term storage are crucial steps that could not be avoided, our results
pointed at ionizing beta-rays as terminal sterilization method for decellularized
grafts followed by frozen dry storage. Indeed, this approach can maintain the
integrity of collagen-based structures and can avoid biomechanical changes, thus
making xenogeneic decellularized tendons a promising candidate for clinical use.
PMID- 28415483
TI - An investigation of electrospun Henna leaves extract-loaded chitosan based
nanofibrous mats for skin tissue engineering.
AB - Wound healing characteristics of some plant extracts have been well known for
many years, and they have been utilized for such applications in traditional way.
Recently electrospun nanofibrous mats showed promising properties for tissue
engineering and especially for skin repair. It is expected that incorporation of
plant extracts into such structures could provide higher performance and
synergistic effect for biomedical and wound healing applications. The final
purpose of this study is to fabricate chitosan based nanofiber mats loaded with a
traditional plant extract of Lawsonia inermis (Henna) leaves to enhance the
antibacterial efficacy and wound healing of the precursor nanofibers. The
morphology, structure, mechanical properties and swelling and weight loss degree
of the electrospun nanofibers have been investigated in this study. Antibacterial
activity, cell biocompatibility evaluations and in vivo wound healing activity of
the abovementioned mats were also studied. The FESEM images of Henna leaves
extract-loaded nanofibers proved that homogeneous, smooth and defect free
nanofibers of 64-87nm in diameter have been prepared. Presence of Henna extract
in the electrospun fibers was approved by Fourier Transform Infrared
spectroscopy. Incorporation of Henna extract into the nanofiber mats exhibited
significant synergistic antibacterial activity against bacterial cells. It was
well supported by the results of cell viability and proliferation of human
foreskin fibroblast cells on the prepared scaffolds. Therefore, the results of
this work showed that Henna leaves extract incorporated chitosan nonwoven mats
have a great potential to be used as the biodegradable, biobased and
antibacterial wound healing dressings.
PMID- 28415484
TI - In vitro evaluation of osteoblastic cells on bacterial cellulose modified with
multi-walled carbon nanotubes as scaffold for bone regeneration.
AB - In this paper we explore the use of native bacterial cellulose (BC) in
combination with functionalized multi-walled carbon nanotubes (MWNTs) as an
original biomaterial, suitable three-dimensional (3D) scaffold for osteoblastic
cell culture. Functionalized MWNTs were mixed with native BC (secreted by
Gluconacetobacter xylinus) with the aim of reinforcing the mechanical properties
of BC. The results indicate that BC-MWNTs scaffolds support osteoblast viability,
adhesion and proliferation at higher levels as compared to traditional culture
substrates. Chemically functionalized MWNTs are also an excellent material to be
used as scaffold because these did not affect cell viability and showed an
enhanced osteoblast adhesion. These results suggest the potential for this
combination of biomaterials, i.e. BC and carbon nanomaterials, as scaffolds for
bone regeneration.
PMID- 28415485
TI - Antimicrobial activity of eumelanin-based hybrids: The role of TiO2 in modulating
the structure and biological performance.
AB - Eco-friendly hybrid Eumelanin-TiO2 nanostructures, recently obtained through in
situ methodology based on hydrothermal route, have shown a striking antimicrobial
activity, after exposure to oxidative environment, even under visible light
induction condition. Nevertheless, the role of each component in defining the
efficacy of these biological properties is far from being clearly defined.
Furthermore, the effect of oxidative step on hybrids structure has not yet
addressed. This study aims at elucidating the role of the ratio between eumelanin
precursor, 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and TiO2, for its
polymerization in defining morphology and structural organization of TiO2-melanin
nanostructures. Furthermore, tests on a Gram-negative Escherichia coli DH5alpha
strain under UV irradiation and even visible light allowed to assess the
contribution of each component, as well as of the TiO2-DHICA charge transfer
complex to overall biological performance. Finally, results of biocide
characterization were combined with spectroscopic evidences to prove that
oxidative treatment induces a marked structural modification in melanin thus
enhancing overall antimicrobial efficacy.
PMID- 28415486
TI - Surface modification of thin film composite membrane by nanoporous titanate
nanoparticles for improving combined organic and inorganic antifouling
properties.
AB - In this study, nanoporous titanate (NT) nanoparticle synthesized by the
solvothermal method was used to modify polyamide layer of thin film composite
membranes with the aim of improving membrane resistances against organic and
inorganic fouling. Thin film nanocomposite membranes (NMs) were synthesized by
adding mNTs (modified nanoparticles) into polyamide selective layer followed by
characterization using different analytical instruments. The results of XPS and
XRD confirmed the presence of mNTs in the polyamide layer of NMs, while FESEM,
AFM, zeta potential and contact angle measurement further supported the changes
in physical and chemical properties of the membrane surface upon mNTs
incorporation. Results of fouling showed that NM1 (the membrane incorporated with
0.01w/v% mNTs) always demonstrated lower degree of flux decline compared to the
control membrane when membranes were tested with organic, inorganic and
multicomponent synthesized water, brackish water or seawater. Besides showing
greater antifouling resistance, the NM also displayed significantly higher water
flux compared to the control M membrane. The findings of this work confirmed the
positive impact of mNTs in improving the properties of NM with respect to fouling
mitigation and flux improvement.
PMID- 28415487
TI - Simultaneous formation and mineralization of star-P(EO-stat-PO) hydrogels.
AB - Natural bone is an organic-inorganic composite of highly ordered collagen fibrils
and ~60-70% nanocrystalline hydroxyapatite (HA) crystals resulting in a high
fracture resistance for various mechanical loading situations. This study aimed
to synthesize highly mineralized hydrogels to mimic the mechanical properties of
cancellous bone. A six armed star molecule functionalized with isocyanate groups
as reactive termini (NCO-sP(EO-stat-PO)) was used to build up a hydrogel matrix,
which was then subsequently mineralized with hydroxyapatite nanocrystals
following the hydrolysis of incorporated alpha-tricalcium phosphate particles.
The advantage of this dual setting approach in comparison to simply adding
unreactive filler particles to the hydrogel was demonstrated to be a strength
improvement by the factor of 30. After 1-28d setting, the mechanical properties
of a composite with 30wt% NCO-sP(EO-stat-PO) such as elasticity (5.3-1.4%),
compression strength (11-23MPa) and E-modulus (211-811MPa) were found to be
similar to the properties of cancellous bone.
PMID- 28415488
TI - Ultrasound stimulated release of gallic acid from chitin hydrogel matrix.
AB - Ultrasound (US) stimulated drug release was examined in this study using a chitin
hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and
anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin
dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA,
with 24h exposure of the solution to water vapor. The GA release from the GA
chitin hydrogel was examined under different US powers of 0-30W at 43kHz. The
effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25mg/cm3) and
chitin concentrations (0.1, 0.5, and 1wt%) on the release behaviors were recorded
under 43kHz US exposure at 30W. Results show that US accelerated the release
efficiencies for all samples. Furthermore, the release efficiency increased
concomitantly with increasing US power, GA loading amount, and decrease of the
chitin concentration. The highest release rate of 0.74MUg/mL.min was obtained
from 0.54mg/cm3 of GA-loaded hydrogel fabricated from a 0.1wt% chitin mixture
solution under 43kHz US exposure at 30W: nine times higher than that of the
sample without US exposure. The hydrogel viscoelasticity demonstrated that the US
irradiation rigidified the material. FT-IR showed that US can break the hydrogen
bonds in the GA-chitin hydrogels.
PMID- 28415489
TI - Design of Salecan-containing semi-IPN hydrogel for amoxicillin delivery.
AB - Salecan is a new linear extracellular beta-glucan. The unique structure and
beneficial properties of Salecan makes it an appealing material in biomedical
applications. In this work, novel drug devices based on Salecan in a hydrogel
matrix of poly(N-(3-dimethylaminopropyl)acrylamide-co-acrylamide) (Salecan/PDA)
were fabricated via free radical polymerization for controlled release of
amoxicillin. It was demonstrated that amoxicillin was efficiently encapsulated
into the developed hydrogels and released in a Salecan dose-dependent and pH
sensitive manner. Furthermore, cell toxicity and adhesion assays confirmed that
these drug carriers were biocompatible. Altogether, this study opens a new avenue
to fabricate hydrogel devices for controlled delivery of drug.
PMID- 28415491
TI - The substitution of the implant and abutment for their analogs in mechanical
studies: In vitro and in silico analysis.
AB - The use of analogs could reduce the cost of mechanical tests involving implant
supported crowns, but it is unclear if it would negatively affect the data
accuracy. This study evaluated the substitution of the implant by implants
analogs or abutment analogs as a support for crowns in mechanical tests, taking
into account stress distribution and fracture load of monolithic lithium
disilicate crowns. Thirty lithium disilicate monolithic crowns were randomized
into three groups according to the set: Implant+abutment (IA); implant
analog+abutment (IAA); abutment analog (AA). The specimens were subjected to
mechanical fatigue (106cycles, 200N, 2Hz) and thermal fatigue (104cycles, 5
degrees -55 degrees C). A final compression load was applied and the maximum
fracture load was recorded. Data were analyzed using one-way ANOVA (alpha=0.05).
The experiment was validated by finite element analysis and the maximum principal
stress was recorded. No statistically significant difference was observed in the
mean fracture load among groups (P>0.05). The failure mode was similar for all
groups with the origin of crack propagation located at the load point
application. Finite element analysis showed similar stress distribution and
stress peak values for all groups. The use of implant's or abutment's analog does
not influence the fracture load and stress distribution for cemented implant
supported crowns.
PMID- 28415490
TI - Poly(ionic liquid) functionalized polypyrrole nanotubes supported gold
nanoparticles: An efficient electrochemical sensor to detect epinephrine.
AB - Poly(ionic liquids) (PILs) have been applied as the linkers between Au
nanoparticles (NPs) and polypyrrole nanotubes (PPyNTs) for the synthesis of
Au/PILs/PPyNTs hybrids. Due to the presence of PILs, high-density and well
dispersed Au NPs have been deposited on the surface of PILs/PPyNTs by anion
exchange with Au precursor and the in-situ reduction of metal ions. The obtained
Au/PILs/PPyNTs hybrids can be used as a good steady electrode material for
sensitively and selectively detecting epinephrine (EP). The catalytic oxidation
peak currents obtained from differential pulse voltammetry (DPV) increased
linearly with increasing EP concentrations in the range of 35-960MUM with a
detection limit of 298.9nM according to the criterion of a signal-to-noise
ratio=3 (S/N=3), respectively, which showed the excellent electrocatalytic
activity towards this significant hormone in human life.
PMID- 28415492
TI - Antibacterial activity of novel peptide derived from Cry1Ab16 toxin and
development of LbL films for foodborne pathogens control.
AB - Escherichia coli is one of the most common etiological agents of diarrhea in
developing countries. The appearance of resistant E. coli prevents treatment of
these infections. Biotechnological products incorporating antimicrobial peptides
are currently being considered in applications to prevent intestinal infections
by these bacteria. The aim of this study was to evaluate the antibacterial
activity of the peptide PcL342-354C, which is derived from the toxin Cry1Ab16
from Bacillus thuringiensis, against E. coli strains. We also report the
preparation, characterization and evaluation of the antibacterial activity of LbL
films containing PcL342-354C. The results showed that the PcL342-354C peptide
inhibited the growth of different strains of E. coli with minimal inhibitory
concentration ranging from 15.62-31.25MUg/mL and minimal bactericidal
concentration was 250MUg/mL, indicating a potential antibacterial activity. The
morphology of an ITO/Cashew gum/PcL342-354C film was analysed using atomic force
microscopy which showed an increase of roughness due to the increase in the
number of layers. The LbL films showed significant antibacterial activity against
E. coli NCTC 9001 in both conditions tested (10 and 20 bilayers). Our results
indicate that the peptide exhibits an antibacterial potential that can be tapped
to develop biomaterials with antibacterial activity for use against foodborne
pathogens.
PMID- 28415493
TI - Multifunctional BaYbF5: Gd/Er upconversion nanoparticles for in vivo tri-modal
upconversion optical, X-ray computed tomography and magnetic resonance imaging.
AB - Development of high-quality upconversion nanoparticles (UCNPs) with combination
of the merits of multiple molecular imaging techniques, such as, upconversion
luminescence (UCL) imaging, X-ray computed tomography (CT), and magnetic
resonance (MR) imaging, could significantly improve the accuracy of biological
diagnosis. In this work, multifunctional BaYbF5: Gd/Er (50:2mol%) UCNPs were
synthesized via a solvothermal method using oleic acid (OA) as surface ligands
(denoted as OA-UCNPs). The OA-UCNPs were further treated by diluted HCl to form
ligand-free UCNPs (LF-UCNPs) for later bioimaging applications. The cytotoxicity
assay in HeLa cells shows low cell toxicity of these LF-UCNPs. Owing to the
efficient UCL of BaYbF5: Gd/Er, the LF-UCNPs were successfully used as
luminescent bioprobe in UCL bioimaging. And, X-ray CT imaging reveals that
BaYbF5: Gd/Er UCNPs can act as potential contrast agents for detection of the
liver and spleen in the live mice owing to the high-Z elements (e.g., Ba, Yb, and
Gd) in host matrix. Moreover, with the addition of Gd, the as-designed UCNPs
exhibit additional positive contrast enhancement in T1-weighted MR imaging. These
findings demonstrate that BaYbF5: Gd/Er UCNPs are potential candidates for tri
modal imaging.
PMID- 28415494
TI - Investigation on Au-nano incorporated pH-sensitive (itaconic acid/acrylic
acid/triethylene glycol) based polymeric biocompatible hydrogels.
AB - The pH-sensitive gold nano hydrogel based on itaconic acid, acrylic acid and
triethylene glycol (GIAT) has been prepared by free radical polymerization viz.
organic solventless approach with different monomer ratios. The nature of bonding
and structural identification of GIAT hydrogels were characterized by FT-IR
spectroscopy. The surface morphology of gold gel was examined using scanning
electron microscopy (SEM). In addition, transmission electron microscopy (TEM)
was used to identify the size of gold nano particles. The in vitro
biocompatibility of GIAT hydrogel has been evaluated in 3T3 fibroblast cell
lines. The obtained results show that gold nano particle incorporated hydrogel
possess ~99% of cell proliferation. Followed by, the impact of gold nano
particles on swelling, surface morphology was studied. The consecutive
preparation of hydrogel, effect of different pH conditions, and stoichiometry of
monomeric units have also been discussed. The degree of swelling was measured in
carbonate buffer solutions for 24h period with varying pH such as 1.2, 6.0, 7.4
and 10.0. The obtained results showed that the stoichiometry of itaconic acid and
gold nano particles plays an essential role in modifying the nature of GIAT
polymeric hydrogels. In conclusion, promising Au-nano incorporated pH-sensitive
bio polymeric hydrogels were prepared and characterized. The unique properties of
these Au-nano hydrogel make them attractive use in biomedical applications.
PMID- 28415495
TI - Silver sulfadiazine immobilized glass as antimicrobial fillers for dental
restorative materials.
AB - Bacterial colonization and biofilm formation on dental resin composites cause
secondary caries that shortens the service life of dental restorative materials.
In this study, commercial barium borosilicate based glass powders, fillers widely
used in dental composites, were covalently immobilized with silver sulfadiazine
to provide antimicrobial effects. The chemical reactions were followed by FT-IR
study, elemental analysis, and energy dispersive spectroscopy (EDS), and the
reaction pathway was confirmed by model compound studies. The resulting glass
powders demonstrated potent antimicrobial effects against Streptococcus mutans
(S. mutans). BisGMA (2,2-bis[4-(2-hydroxy-3-methacrylyloxypropoxy)phenyl]
propane)-based dental resins containing 2% to 10% of the new silver sulfadiazine
glass powders exhibited powerful and durable antimicrobial efficacy against S.
mutans. The mechanical properties of the antimicrobial resins were not negatively
affected by the silver sulfadiazine glass powders, making them attractive
candidates as antimicrobial fillers for dental composites and other related
biomedical applications.
PMID- 28415496
TI - A novel long-acting biodegradable depot formulation of anastrozole for breast
cancer therapy.
AB - The purpose of the present study was to fabricate PLGA 50:50 and PLA microspheres
for controlled delivery of anastrozole. The microspheres were prepared by oil-in
water (o/w) emulsion/solvent evaporation technique and evaluated for particle
size and encapsulation. The optimised formulations were studied for solid state
characterization, in vitro release and pharmacokinetic studies. The maximum
encapsulation efficiency for PLGA 50:50 and PLA microspheres with 40:1 polymer -
drug ratio was observed to be 78.4+/-2.5 and 87.7+/-2.6%. The solid state
characterization confirmed dispersion of drug at the molecular level in the
polymeric matrix. Microspheres were spherical in shape with a very smooth surface
texture. Drug release was found to be in a sustained fashion, releasing
constantly up to 720h (30days) for PLGA and 60days for PLA microspheres. The
pharmacokinetic study data revealed that the intramuscular administration of PLA
microspheres showed improved pharmacokinetic profile as compared to PLGA
microspheres, and therefore this formulation can be considered as the best
optimised formulation with sustained exposure of the drug in vivo compared to
other microspheres. From experimental results, PLA microspheres demonstrate the
feasibility of employing biodegradable depot polymeric microspheres of
anastrozole for long-term treatment of breast cancer.
PMID- 28415497
TI - Modeling and optimization of gelatin-chitosan micro-carriers preparation for soft
tissue engineering: Using Response Surface Methodology.
AB - Electrospray ionization is a wide spread technique for producing polymeric
microcarriers (MCs) by applying electrostatic force and ionic cross-linker,
simultaneously. In this study, fabrication process of gelatin-chitosan MCs and
its optimization using the Response Surface Methodology (RSM) is reported.
Gelatin/chitosan (G/C) blend ratio, applied voltage and feeding flow rate, their
individual and interaction effects on the diameter and mechanical strength of the
MCs were investigated. The obtained models for diameter and mechanical strength
of MCs have a quadratic relationship with G/C blend ratio, applied voltage and
feeding flow rate. Using the desirability curve, optimized G/C blend ratios that
are introduced, include the desirable quantities for MCs diameter and mechanical
strength. MCs of the same desirable diameter (350MUm) and different G/C blend
ratio (1, 2, and 3) were fabricated and their elasticity was investigated via
Atomic Force Microscopy (AFM). The biocompatibility of the MCs was evaluated
using MTT assay. The results showed that human Umbilical Cord Mesenchymal Stem
Cells (hUCMSCs) could attach and proliferate on fabricated MCs during 7days of
culturing especially on those prepared with G/C blend ratios of 1 and 2. Such
gelatin-chitosan MCs may be considered as a promising candidate for injectable
tissue engineering scaffolds, supporting attachment and proliferation of hUCMSCs.
PMID- 28415498
TI - Reduction-sensitive micelles self-assembled from amphiphilic chondroitin sulfate
A-deoxycholic acid conjugate for triggered release of doxorubicin.
AB - Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed.
CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The
bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous
medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is
0.047mg/mL, and its mean diameter is 387nm. The anticancer drug doxorubicin (DOX)
was chosen as a model drug, and was effectively encapsulated into the micelles
with high loading efficiency. Reduction-sensitive micelles and reduction
insensitive control micelles displayed similar DOX release behavior in phosphate
buffered saline (PBS, pH7.4). Notably, DOX release from the reduction-sensitive
micelles in vitro was accelerated in the presence of 20mM glutathione-containing
PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles
exhibited intracellular reduction-responsive characteristics in human gastric
cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM).
Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than
reduction-insensitive control micelles in HGC-27 cells. These results suggested
that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular
targeted carriers of anticancer drugs.
PMID- 28415499
TI - Antibacterial effect of PEO coating with silver on AA7075.
AB - In this work, plasma electrolytic oxidation (PEO) coatings were produced on
AA7075 using alkaline solution containing silicates compounds and silver
micrometric particles in order to give to the coating an antimicrobial effect. In
the optic of circular economy, silver chloride derived from the acid pre
treatment of electronic scraps was used as raw material and successively silver
powders were synthesized from silver chloride solution using glucose syrup as
reducing agent. The coatings were characterized by scanning electron microscope
(SEM), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS),
potentiodynamic polarization test and antimicrobial tests. The results evidenced
that the obtained coatings were homogenous and give to the samples higher
corrosion resistance than untreated alloy. The silver particles, found both
inside and outside of the pores that characterize the PEO layer, produced an
efficacious antimicrobial effect both against E. coli and S. aureus.
PMID- 28415500
TI - Sustained release of simvastatin from hollow carbonated hydroxyapatite
microspheres prepared by aspartic acid and sodium dodecyl sulfate.
AB - Hollow carbonated hydroxyapatite (HCHAp) microspheres as simvastatin (SV)
sustained-release vehicles were fabricated through a novel and simple one-step
biomimetic strategy. Firstly, hollow CaCO3 microspheres were precipitated through
the reaction of CaCl2 with Na2CO3 in the presence of aspartic acid and sodium
dodecyl sulfate. Then, the as-prepared hollow CaCO3 microspheres were transformed
into HCHAp microspheres with a controlled anion-exchange method. The HCHAp
microspheres were 3-5MUm with a shell thickness of 0.5-1MUm and were constructed
of short needle nanoparticles. The HCHAp microspheres were then loaded with SV,
exhibiting excellent drug-loading capacity and sustained release properties.
These results present a new material synthesis strategy for HCHAp microspheres
and suggest that the as-prepared HCHAp microspheres are promising for
applications in drug delivery.
PMID- 28415501
TI - Fabrication of new magnetite-graphene nanocomposite and comparison of its laser
hyperthermia properties with conventionally prepared magnetite-graphene hybrid.
AB - A single step supercritical method was introduced for synthesis of "magnetite -
reduced graphene oxide (M-rGO)" composite in supercritical methanol. Modified
surface, smaller size, lesser cytotoxicity, and homogenous dispersion of Fe3O4
nanoparticles on the graphene surface were advantages of this new M-rGO composite
in comparison to the materials synthesized by conventional wet chemical method (M
GO). Nanocomposites were injected in tissue equivalent phantoms of agarose gel in
10mg/g dosage, and were irradiated by a 1600mW laser beam at wavelength of 800
810nm. The M-rGO and M-GO were found to be the most and the least efficient
samples for increasing the temperature of the phantom. As for mathematical
analysis of the heating process, a heat transfer model was developed and solved
by the COMSOL Multiphysics software. Results showed an appreciable agreement with
the experiments and revealed enhancement in thermal conductivity and light
absorption coefficient of tissue by injecting of M-rGO sample. Our findings
showed that M-rGO is a promising material for laser hyperthermia, which can
deposit adequate heat dose with desirable effect in the tumorous cells in a short
period.
PMID- 28415502
TI - Antimicrobial textiles: Biogenic silver nanoparticles against Candida and
Xanthomonas.
AB - This paper introduces cotton fibers impregnated with biogenic silver
nanoparticles (AgNPs), synthesized from a Fusarium oxysporum fungal filtrate (FF)
solution, and open up the possibility for their use in medical environment and
agriculture clothing as means to avoid microbial spreading. After thorough AgNPs
characterization, regarding their physical, chemical and biochemical properties,
Minimum Inhibitory Concentrations (MIC) against some human and orange tree
pathogens were determined. We report the strong AgNPs activity against Candida
parapsilosis and Xanthomonas axonopodis pv. citri (Xac) that was morphologically
characterized, pointing to strong AgNPs effects on microorganisms' membranes.
Cotton fibers were then impregnated with AgNPs suspension and these maintained
strong antimicrobial activity even after repeated mechanical washing cycles (up
to 10). Reported data might point to an application for biogenic AgNPs as potent
agrochemicals, as well as, to their application in textiles for antiseptic
clothing for medical and agronomic applications.
PMID- 28415503
TI - Synthesis of nanosized 58S bioactive glass particles by a three-dimensional
ordered macroporous carbon template.
AB - Nanosized 58S bioactive glass (BG) particles were synthesized by using a three
dimensional ordered macroporous carbon template (OMC) with a pore size of 400nm.
The obtained 58S BG particles possessed a diameter of 300nm, narrow size
distribution and uniform spherical morphology. 58S/gelatin composites were
prepared and showed much better mechanical properties than pure gelatin. The
narrow size distribution of the 58S particles replicated from OMC was confirmed
crucial to the mechanical properties of the 58S/gelatin composite, comparing to
the contrast sample prepared with polydispersed particles. The outstanding
bioactivity of the 58S BG particles was confirmed by inducing the formation of
carbonated hydroxyapatite on the 58S/gelatin composite surface. This work showed
a successful example that OMC template could be used to synthesize particles
requiring a robust reaction condition, and a particle synthesis method that could
well control particle size distribution was important for preparing materials
with outstanding mechanical properties.
PMID- 28415504
TI - In vitro evaluation of hydroxyapatite coatings with (002) crystallographic
texture deposited by micro-plasma spraying.
AB - Hydroxyapatite (HA) coatings are usually deposited on the metallic implant to
increase the biocompatibility and protect the bloodstream from harmful metal
ions. Atmospheric plasma spray (APS) is known as a cost effective deposition
method. However, the low crystallinity of APS deposited coating accelerates its
dissolution in body fluid. We used micro-plasma spray (MPS) to develop chemically
stable HA coatings, and performed APS as reference. Results showed that MPS
deposited coatings exhibited (002) crystallographic texture while the reference
sample did not. The texture intensity and crystallinity were improved by
shortening stand-off distance. These suggested that different formation
procedures of HA coatings were involved and three mechanisms were proposed by
sketching typical splats. To evaluate the chemical stability of the coatings in a
physiological environment, in vitro experiments were performed in Hanks'
solution. Well crystallized (~100%) HA coating with the strongest
crystallographic texture exhibited superior stability up to 14days. Crystals with
(002) orientation was more stable than that with (211) orientation. Hence
columnar structure with nanopores emerged on the coating surface after
incubation, and this may facilitate the future osteoblast growth. Furthermore, HA
coating with weak and no crystallographic texture induced apatite layer. However,
vertical cracks and cleavage at coating-apatite interface may cause coating
separation.
PMID- 28415505
TI - A new method to produce macroporous Mg-phosphate bone growth substitutes.
AB - This paper is a sequel to our previous effort in developing Mg-phosphate
orthopedic cements using amorphous Mg-phosphate (AMP) as the precursor. In this
paper, we report a new real-time in situ technique to create macroporous bone
growth substitute (BGS). The method uses biodegradable Mg-particles as the
porogen. As opposed to the conventional wisdom of providing corrosion protection
layers to biodegradable Mg-alloys, the present method uses the fast corrosion
kinetics of Mg to create macropores in real time during the setting of the
cement. An aqueous solution of PVA was used as the setting solution. Using this
technique, a macroporous cement containing up to 91% porosity is obtained, as
determined by pycnometry. Due to formation of H2 gas bubbles from corrosion of
Mg, the cement becomes macroporous. The pore sizes as big as 760MUm were
observed. The results of SBF soaking indicated change in crystallinity as
confirmed via scanning electron microscopy (SEM) and X-ray diffraction (XRD). Our
in vitro cytocompatibility evaluation also revealed that the macroporous bone
growth substitute composed of bobierrite is cytocompatible and can improve gene
expression.
PMID- 28415506
TI - The bactericidal mechanism of action against Staphylococcus aureus for AgO
nanoparticles.
AB - To identify the mechanistic effects of AgO nanoparticles on Gram-positive
bacteria, S. aureus cells suspended in phosphate buffer solution (PBS) and
deionized water were separately treated using AgO nanoparticles at different
concentrations. The phase composition changes of the bactericide after killing S.
aureus and the cellular responses of S. aureus to AgO were characterized by X-ray
diffraction, atomic absorption spectrophotometer, scanning electron microscopy,
transmission electron microscopy, and energy dispersive spectroscopy. The results
show that AgO nanoparticles could kill S. aureus suspended in PBS and deionized
water. The bactericidal effect of AgO bactericide against S. aureus in water was
better than that in PBS, due to the formation of Ag3PO4 from the reaction between
AgO and PBS. AgO nanoparticles exerted their bactericidal activity by multiple
processes. AgO nanoparticles adhered to the surface of S. aureus cells firstly,
then induced physical alterations in cell morphology and released silver ions,
leading to initial injuries of cell membrane. Once membrane damage occurred, they
entered the cells, and damaged the intracellular materials, eventually causing
severe morphological and structural injuries to the cells and leakage of
cytoplasm.
PMID- 28415507
TI - Influences of doping mesoporous magnesium silicate on water absorption, drug
release, degradability, apatite-mineralization and primary cells responses to
calcium sulfate based bone cements.
AB - In this study, composite cements containing mesoporous magnesium silicate (m-MS)
and calcium sulfate (CS) were fabricated. The results revealed that the setting
time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the
increase of m-MS content while the compressive strength suffered a little loss.
The doping of m-MS improved the water absorption, drug release (vancomycin) and
degradability of the m-MSC in Tris-HCl solution (pH=7.4). In addition, addition
of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid
(SBF), indicating good bioactivity. For cell cultural experiments, the results
revealed that the m-MSC promoted the cells adhesion and proliferation, and
improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing
good cytocompatibility. It could be suggested that the m-MSC might be promising
cements biomaterials for bone tissue regeneration.
PMID- 28415508
TI - Magneto-elastic biosensors: Influence of different thiols on pathogen capture
efficiency.
AB - Magneto-elastic biosensors have mass sensitivity to biological species, offering
reliability and reproducibility in the detection of pathogens such as Escherichia
coli. In this work, amorphous ribbons of Metglas 2826MB3 were coated with layers
of Cr and Au by DC magnetron sputtering and cut to 5mm*1mm. The influence of
different thiols on captured pathogens was studied. The compounds cystamine
(CYS), cysteamine (CYSTE) and mercaptopropionic acid (MPA) were deposited on Au
covered surfaces, followed by antibodies. The roughness parameters Ra and Rq were
determined using atomic force microscopy (AFM) and micrographs from scanning
electron microscopy with a field emission gun (FESEM) were also utilized.
Biosensors formed with MPA showed an increased efficiency for attracting E. coli
compared to biosensors with CYS and CYSTE, but large standard deviations were
observed, making reproducibility and reliability difficult for that biosensor.
Sensors tested with CYSTE showed greater efficiency and a lower detection limit
than sensors with CYS. The results indicated that the size of the carbon chain
and the terminal grouping influence the effectiveness of immobilization on
magneto-elastic biosensors.
PMID- 28415509
TI - Preparation and evaluation of a novel anticancer drug delivery carrier for 5
Fluorouracil using synthetic bola-amphiphile based on lysine as polar heads.
AB - A novel bolaamphiphile surfactant N,N'-(dodecane-1, 12-diyl) bis (2,6
diaminohexanamide) (DADL) was designed and synthesized using l-lysine and 1,12
diaminododecane as the hydrophilic and hydrophobic part, respectively. After
separation and purification, the structure of the synthetic bolaamphiphile
surfactant was verified by FTIR, MS and 1H NMR. The synthetic bolaamphiphile was
able to self-assemble to form vesicles. After formulation screening, vesicles
loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by
sonication and were examined by dynamic light scattering and transmission
electron microscopy. Micro-FTIR was applied to investigate the conformation of
the bola molecules within the vesicle membrane. The release profile of the
vesicles showed a pH-sensitive and sustained release. No significant toxicity was
observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu
loaded vesicles on H22 tumor-bearing mice was remarkably high due to the EPR
effects. These results show that our novel bolaamphiphile derived from lysine has
excellent potential as a pH-sensitive drug carrier.
PMID- 28415510
TI - On the passive and semiconducting behavior of severely deformed pure titanium in
Ringer's physiological solution at 37 degrees C: A trial of the point defect
model.
AB - The effects of sever plastic deformation through multi-pass accumulative roll
bonding on the passive and semiconducting behavior of pure titanium is evaluated
in Ringer's physiological solution at 37 degrees C in the present paper. Produced
results by polarization plots and electrochemical impedance spectroscopy
measurements revealed a significant advance in the passive response of the nano
grained sample compared to that of the annealed pure titanium. Also, Mott
Schottky test results of the nano-grained pure titanium represented a lower donor
density and reduced flat-band potential in the formed passive film in comparison
with the annealed sample. Moreover, based on the Mott-Schottky analysis in
conjunction with the point defect model, it was suggested that with increase in
formation potential, the calculated donor density of both annealed and nano
grained samples decreases exponentially and the thickness of the passive film
linearly increases. These observations were consistent with the point defect
model predictions, considering that the point defects within the passive film are
metal interstitials, oxygen vacancies, or both. From the viewpoint of passive and
semiconducting behavior, nano-grained pure titanium appeared to be more suitable
for implant applications in simulate human body environment compared to annealed
pure titanium.
PMID- 28415511
TI - Facile synthesis and characterization of novel rapid-setting spherical sub-micron
bioactive glasses cements and their biocompatibility in vitro.
AB - Dental pulp vitality is extremely important for the tooth viability, since it
provides nutrition and forms the dentin. Bioactive glasses (BGs) may be promising
materials for pulp repair due to their excellent abilities of rapidly bonding to
bone and stimulating new bone growth. However, the unsatisfied handling property,
low plasticity, and poor rapid-setting property of traditional BGs limit its
application in vital pulp therapy. Spherical bioactive glasses (SBGs) exhibited
higher osteogenesis and odontogenic differentiation than irregular BGs. This
study focuses on the application of SBGs with rapid setting property for dental
pulp repair. Here, SBGs with various compositions were successfully synthesized
by a sol-gel process using dodecylamine (DDA) served as both a catalyst and a
template. The maximum content of CaO in SBGs was about 15%. The non-bridge oxygen
amounts of the SiO network and the apatite-forming ability increased with the
content proportion of CaO and P2O5. Bioactive glass pulp capping materials
(BGPCMs) were prepared by mixing the SBGs powders and the phosphate buffer
solution (PBS). The K3CaH(PO4)2 and hydroxyapatite (HA) formed between SBGs
particles as soon as they were mixed with PBS solution. The compressive strengths
of fully set BCPCM-2 molded were measured to be 31.76+/-1.9577MPa after setting
for 24h. The K3CaH(PO4)2 and the low crystallinity HA phases at the initial stage
of solidification transformed to crystalline HA for 3days, and the compressive
strength was still higher than 10MPa. Additionally, SBG-2 with a designed molar
composition of 35% SiO2, 55% CaO and 10% P2O5 more promoted dental pulp cell
proliferation, and could be potential pulp capping applications.
PMID- 28415512
TI - Study of epithelial differentiation and protein expression of keratinocyte
mesenchyme stem cell co-cultivation on electrospun nylon/B. vulgaris extract
composite scaffold.
AB - Employing of the composite electrospun scaffold containing herbal extract in
conjugation with co-culturing of cells can open up new window to the design of
efficient biomaterials for skin tissue regeneration. Here, we introduce the
synergistic effect of composite electrospun nanofibrous scaffold of nylon66
loaded with Beta vulgaris (B. vulgaris) (extract of beet roots, a plants whose
widely used in Iranian folk medicine as wound healing medicine) and co-culture of
mesenchymal stem-cells (MSCs)-human keratinocyte (H-keratino) differentiation
towards epithelial lineage. In vitro biocompatibility was examined through MTT
assay and epithelial differentiation checked by real-time PCR and
immunocytochemistry (ICC) assay after co-culturing of MSCs and H-keratino on
proposed scaffold. Significant enhancement in cell proliferation was detected
after cell culturing on the composite type of electrospun scaffold containing B.
vulgaris. Moreover, after 14days of co-culturing process, gene expression results
revealed that both composite and non-composite nylon66 electrospun scaffold
promote epithelial differentiation compared to mono-cell culturing of H-keratino
in terms of several markers as Cytokeratin 10, Cytokeratin 14 and Involucrin and
ICC of some dermal proteins like Cytokeratin 14 and Loricrin. To the best of our
knowledge, findings of this study will introduce new way for the generation of
novel biomaterials for the development of current skin tissue engineering.
PMID- 28415513
TI - Evaluation of radiolabeled curcumin-loaded solid lipid nanoparticles usage as an
imaging agent in liver-spleen scintigraphy.
AB - Curcumin-loaded solid lipid nanoparticles (C-SLNs) were prepared using micro
emulsion and ultrasonication methods in the first stage of this study to
determine the role of C-SLN on liver-spleen scintigraphy. It was concluded that
the curcumin that was encapsulated in solid lipid nanoparticles had a beta'
polymorph structure according to the X-ray diffraction (XRD) analysis. It was
concluded that these particles were at nano scale according to the laser
diffraction (LD) analysis. Fourier transform infrared spectroscopy (FT-IR)
analysis suggested an interaction between the curcumin and the solid lipid
matrix, and the curcumin was loaded on the solid lipid nanoparticles. Moreover,
the particles were concluded to be spherical and at nanoscale according to the
scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
images. On the other hand, thermogravimetric analysis (TGA) suggested that the
curcumin loaded solid nanoparticles were stable against the temperature. C-SLNs
were labeled with Technetium-99m (99mTc) radioisotope in the second stage of the
study, then using scintigraphic methods in-vivo studies were performed on New
Zealand rabbit and made a comparison with Phytate colloid, routinely used in
liver-spleen scintigraphy. After analyzing the images and the biological
distributions obtained from the experiments, uptake was observed in the liver and
the spleen. Following from the experiment results, 99mTc-labeled C-SLNs was
concluded to be a possible imaging agent. In particular, it could be a new
radiopharmaceutical alternative to 99mTc-labeled compounds that are used in liver
and spleen imaging in colloid scintigraphy.
PMID- 28415514
TI - Synthesis and characterization of cycloaliphatic hydrophilic polyurethanes,
modified with l-ascorbic acid, as materials for soft tissue regeneration.
AB - In this paper we described synthesis and characteristic of obtained hydrophilic
polyurethanes (PURs) modified with ascorbic acid (commonly known as vitamin C).
Such materials may find an application in the biomedical field, for example in
the regenerative medicine of soft tissues, according to ascorbic acid wide
influence on tissue regeneration Flora (2009), Szymanska-Pasternak et al. (2011),
Taikarimi and Ibrahim (2011), Myrvik and Volk (1954), Li et al. (2001), Cursino
et al. (2005) . Hydrophilic PURs were obtained with the use of amorphous
alpha,omega-dihydroxy(ethylene-butylene adipate) (dHEBA) polyol, 1,4-butanediol
(BDO) chain extender and aliphatic 4,4'-methylenebis(cyclohexyl isocyanate)
(HMDI). HMDI was chosen as a nontoxic diisocyanate, suitable for biomedical PUR
synthesis. Modification with l-ascorbic acid (AA) was performed to improve
obtained PUR materials biocompatibility. Chemical structure of obtained PURs was
provided and confirmed by Fourier transform infrared spectroscopy (FTIR) and
Proton nuclear magnetic resonance spectroscopy (1HNMR). Differential scanning
calorimetry (DSC) was used to indicate the influence of ascorbic acid
modification on such parameters as glass transition temperature, melting
temperature and melting enthalpies of obtained materials. To determine how these
materials may potentially behave, after implementation in tissue, degradation
behavior of obtained PURs in various chemical environments, which were
represented by canola oil, saline solution, distilled water and phosphate
buffered saline (PBS) was estimated. The influence of AA on hydrophilic
hydrophobic character of obtained PURs was established by contact angle study.
This experiment revealed that ascorbic acid significantly improves hydrophilicity
of obtained PUR materials and the same cause that they are more suitable
candidates for biomedical applications. Good hemocompatibility characteristic of
studied PUR materials was confirmed by the hemocompatibility test with human
blood. Microbiological tests were carried out to indicate the microbiological
sensitivity of obtained PURs. Results of performed studies showed that obtained
AA-modified PUR materials may find an application in soft tissue regeneration.
PMID- 28415515
TI - Highly selective thiocyanate optochemical sensor based on manganese(III)-salophen
ionophore.
AB - We report on the development of optochemical sensor based on Mn(III)-salophen
ionophore. The sensor was prepared by embedding the ionophore in a plasticized
poly (vinyl chloride) impregnated with the chromoionophore ETH7075. Optical
response to thiocyanate occurred due to thiocyanate extraction into the polymer
via formation of strong complex with the ionophore and simultaneous protonation
of the indicator dye yielding the optical response at 545nm. The developed
optochemical sensor exhibited high selectivity for thiocyanate over other anions
including the most lipophilic species such as salicylate and perchlorate. For
instance, the optical selectivity coefficients, logKSCN,anionopt, were as follow:
ClO4-=-5.8; Sal-=-4.0; NO3-?-6. Further, the thiocyanate optical selectivity
obtained using the present optochemical sensor was greatly enhanced in comparison
with that obtained using an anion-exchanger based sensor. Also, the optimized
optochemical sensor exhibited micro-molar detection limit with 2min response time
at pH4.5 using acetate buffer. The reversibility of the optimized sensor was poor
due to strong ligation of the thiocyanate to the central Metal ion, log K=14.1,
which can be overcome by soaking the optode in sodium hydroxide followed by
soaking in buffer solution. The developed sensor was utilized successfully for
the determination of thiocyanate in human saliva and in spiked saliva samples.
PMID- 28415516
TI - Acceleration of bone regeneration in bioactive glass/gelatin composite scaffolds
seeded with bone marrow-derived mesenchymal stem cells over-expressing bone
morphogenetic protein-7.
AB - In this research, the osteoinduction effect of a novel variant of bone
morphogenetic protein-7 (BMP-7), delivered through bone marrow mesenchymal stem
cells (BM-MSCs) seeded on bioactive glass/gelatin nanocomposite scaffolds, was
evaluated in a calvarial critical size defect in rats. After being harvested and
characterized in vitro, BM-MSCs were infected by a plasmid vector containing BMP
7 encoding gene enriched with a heparin-binding site (B2BMP-7) to assess its
osteogenic effects in vivo. The animals were randomly categorized into three
groups receiving the scaffold alone (group I), the scaffold seeded with BM-MSCs
(group II), and the scaffold seeded with manipulated BM-MSCs (group III). After
2, 4 and 12 postoperative weeks, the animals were sacrificed and the harvested
specimens were analyzed using histological and immunohistochemical staining. The
results of in vitro tests (preliminary screening) showed that the synthesized
scaffolds were biocompatible constructs supporting cell attachment and expansion.
The in vivo results revealed higher osteogenesis in the defects filled with the
B2BMP-7 excreting BM-MSCs/scaffolds compared to the other two groups. After
12weeks of implantation, fully mature newly formed bone was detected throughout
the damaged site, which indicates a synergistic effect of cells, scaffolds and
growth factors in the process of tissue regeneration. Therefore, bioactive glass
containing scaffolds pre-seeded with manipulated BM-MSCs exhibit an effective
combination to improve osteogenesis in bone defects, and the approach followed in
this work could have a significant impact in the development of novel tissue
engineering constructs.
PMID- 28415517
TI - Fabrication of novel biodegradable porous bone scaffolds based on amphiphilic
hydroxyapatite nanorods.
AB - This paper describes a new synthetic strategy and biological application for
novel amphiphilic hydroxyapatite (HAp) nanorods. The prepared HAp nanorods were
able to be dispersed in water, ethyl alcohol and cyclohexane. The co-anchoring of
the multidentate ligands of PEG 20000 and hydrophobic oleic acid (OA) on the
rods' surfaces endowed them with excellent amphibious properties. Utilizing
amphiphilic HAp nanorods with excellent biocompatibility as the inorganic phase,
human-like collagen (HLC) as the organic phase and natural genipin as the cross
linker, optimal HLC/HAp porous scaffolds (HLC: HAp=1:4, w/w) were fabricated. The
compression stress and three-point bending strength of the scaffolds with pore
diameters of 150 to 200MUm reached approximately 3.4MPa and 5.4MPa, respectively,
and their porosity was 77.35+/-3.75%. Cytological tests showed that HLC/HAp
scaffolds could contribute to cell proliferation and differentiation. The results
indicated that these novel amphiphilic HAp nanorods can be expected to become
recognized as an excellent inorganic material for the porous scaffolds used in
repairing bone and related applications.
PMID- 28415518
TI - Antimicrobial property, cytocompatibility and corrosion resistance of Zn-doped
ZrO2/TiO2 coatings on Ti6Al4V implants.
AB - Zn-doped ZrO2/TiO2 porous coatings (Zn-ZrO2/TiO2) were prepared on the surface of
titanium alloy (Ti6Al4V) by a hybrid approach of magnetron sputtering and micro
arc oxidation (MAO). The microstructures, phase constituents and elemental states
of the coating were investigated by scanning electron microscope (SEM) equipped
with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and X-ray
photoelectron spectroscopy (XPS). The results demonstrate that the Zn-ZrO2/TiO2
coatings are porous and its thickness is approximately 13MUm. The major phases in
the oxidation coating are tetragonal ZrO2 (t-ZrO2), cubic ZrO2 (c-ZrO2) and
rutile TiO2. XPS result reveals that Zn exists as ZnO in the Zn-ZrO2/TiO2
coatings. The biological experiments indicate that Zn-ZrO2/TiO2 coatings exhibit
not only excellent antibacterial property against Gram-positive Staphylococcus
aureus (S. aureus), but also favorable cytocompatibility. In addition, the
corrosion resistance of the coating is also appreciably improved in the simulated
body fluids (SBF), which can ensure better biocompatibility in body fluids.
PMID- 28415519
TI - Fabrication of thermal sensitive folic acid based supramolecular hybrid gels for
injectable drug release gels.
AB - Thermal sensitive supramolecular hybrid gels for injectable drug release were
prepared by adding different amounts of agar into folic acid (FA) gelator. The
gelation temperature was modulated in order to form injectable gel with body
temperature (37 degrees C). Such kind of folic acid-agar (FAG) hybrid gel makes
it possible to use supramolecular gel as injectable drug loaded gels for drug
release. FT-IR and UV-vis spectra indicate that agar macromolecules involve in
the self-assembly process through intermolecular H-bonding and pi-pi stacking
interactions with FA molecules. The SEM and TEM images demonstrate that the fiber
diameter of FAG hybrid gel is about 20nm, much smaller than that of FA gel
(40nm). However, FAG hybrid has a denser nano-fibrous network structure than FA
gels. Moreover, FAG hybrid gel is endowed with a more ordered network structure
and a little better crystallization capability by adding agar. FAG hybrid gel
also shows a shear-thinning behavior but the shear viscosity is about 2 times
higher than that of FA gel. Compared with FA gel, the storage (G') and loss (G")
moduli of the FAG gel are higher, which implies an enhanced gel strength. At the
same time, both FA and FAG gels are facilely affected by some external factors
such as acid, base and salts. In acidic or basic conditions, the strength became
weak and the gelation temperature (Tg) decreased. While, within certain
concentrations, the salt (NaCl) increased the gel strength and Tg. FAG gel
suffered lower mass loss and owned better stability in different pH solutions
compared with pure FA gel. The release behavior of the FA and injectable FAG gels
was investigated by using Rhodamine B as a mimic model drug. FAG hybrid gel shows
a long release profile and the release time is 3 times longer than that of FA
gel, up to 30h, and the accumulative release amount reaches about 86%. So it is a
potential injectable gel for sustained release drug delivery system.
PMID- 28415520
TI - Tuneable hydrolytic degradation of poly(l-lactide) scaffolds triggered by ZnO
nanoparticles.
AB - In this work we fabricate porous PLLA and PLLA/ZnO scaffolds with porosities
ranging from 10 to 90% and average pore diameter of 125-250MUm by solvent
casting/particulate leaching method. The structural evolution of PLLA/ZnO
scaffolds during their in vitro degradation in phosphate buffered saline (PBS) at
physiological pH (7.4) has been studied as a function of porosity and obtained
results were compared to plain PLLA scaffolds. The changes induced upon the
hydrolytic degradation of scaffolds have been explored by measuring the pH
changes of the medium, the mass loss, thermal transitions, crystalline structure,
thermal stability and the morphological changes. It is shown that the degradation
profile of scaffolds could be successfully modified by tuning both the amount of
ZnO nanoparticles and by varying the scaffold porosity. Results reveal that the
water dissociated on ZnO nanoparticle surfaces initiate hydrolytic degradation
reactions by reducing the strength of the chemical bonds of the adjacent PLLA
chains, causing them to further divide into water-soluble oligomers. Obtained
results may be useful towards the development of antibacterial porous structures
with tuneable degradation rates to be used as a substrate for the growth of
different kind of cells and tissues.
PMID- 28415521
TI - Effect of halloysite nanotubes on the structure and function of important
multiple blood components.
AB - Many researchers have investigated the application of halloysite nanotubes (HNTs)
in biomedicine, because of their special nanoscale hollow tubular structure.
Although the cytocompatibility of HNTs has been studied, their blood
compatibility has not been systematically investigated. In this work, the effect
of HNTs on the structure and function of different blood components has been
studied, including the morphology and hemolysis of red blood cells (RBCs). Based
on scanning electron microscopy (SEM) observations, optical density test and flow
cytometry analysis, we found that HNTs can affect the morphology and membrane
integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way.
In particular, based on UV-vis absorption spectra, fluorescence spectra and
circular dichroism (CD) spectra, HNTs can alter the secondary structure and
conformation of human fibrinogen and gamma-globulins. In addition, the detection
of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger
complement activation. In the blood clotting assay, HNTs were found to
significantly prolong the activated partial thromboplastin time (APTT), shorten
the prothrombin time (PT) of platelet-poor plasma (PPP), and change the
thromboelastography (TEG) parameters of whole blood coagulation. Furthermore,
confocal laser scanning microscopy and flow cytometry analysis were used to test
intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW
264.7 was found to be content-dependent, but not time-dependent. These findings
provide insight for the potential use of HNTs as biofriendly nanocontainers for
biomaterials in vivo.
PMID- 28415522
TI - Biocompatible nanocomposite scaffolds based on copolymer-grafted chitosan for
bone tissue engineering with drug delivery capability.
AB - Significant efforts have been made to develop a suitable biocompatible scaffold
for bone tissue engineering. In this work, a chitosan-graft-poly(acrylic acid-co
acrylamide)/hydroxyapatite nanocomposite scaffold was synthesized through a novel
multi-step route. The prepared scaffolds were characterized for crystallinity,
morphology, elemental analysis, chemical bonds, and pores size in their
structure. The mechanical properties (i.e. compressive strength and elastic
modulus) of the scaffolds were examined. Further, the biocompatibility of
scaffolds was determined by MTT assays on HUGU cells. The result of cell culture
experiments demonstrated that the prepared scaffolds have good cytocompatibility
without any cytotoxicity, and with the incorporation of hydroxyapatite in their
structure improves cell viability and proliferation. Finally, celecoxib as a
model drug was efficiently loaded into the prepared scaffolds because of the
large specific surface area. The in vitro release of the drug displayed a
biphasic pattern with a low initial burst and a sustained release of up to
14days. Furthermore, different release kinetic models were employed for the
description of the release process. The results suggested that the prepared
cytocompatible and non-toxic nanocomposite scaffolds might be efficient implants
and drug carriers in bone-tissue engineering.
PMID- 28415523
TI - Simultaneous voltammetric analysis of anti-ulcer and D2-antagonist agents in
binary mixture using redox sensor and their determination in human serum.
AB - Pencil graphite electrode was successfully modified with a thin film of poly
(eriochrome black T) and applied for the sensitive and selective voltammetric
simultaneous determination of pantoprazole sodium and domperidone in a binary
mixture. The preparation and basic electrochemical behavior of poly (eriochrome
black T) film on the Pencil graphite electrode were investigated. The modified
electrode has exhibited very high electro-catalytic activity towards the cited
mixture. The anodic peaks of the both species were well defined with enhanced
oxidation peak currents. Under the optimum conditions, the linearity ranges were
0.4-55*10-7M and 0.1-34*10-7M for pantoprazole sodium and domperidone,
respectively with detection limits of 0.12*10-7M and 0.04*10-7M for pantoprazole
sodium and domperidone, respectively. The proposed sensor has been successfully
applied in the analysis of pantoprazole sodium and domperidone in synthetic
binary mixtures and human serum.
PMID- 28415524
TI - Biomolecule-assisted synthesis of Ag/reduced graphene oxide nanocomposite with
excellent electrocatalytic and antibacterial performance.
AB - In this work, an environmentally friendly method was applied for the synthesis of
aqueous suspension of l-cysteine modified Ag nanoparticles (NPs)-decorated
reduced graphene oxide (rGO) nanocomposite. l-cysteine played a triple role as
reducing agent, stabilizer and linker of Ag NPs onto the surface of rGO. The
resultant nanocomposite was characterized by Fourier transform infrared
spectroscopy (FT-IR), X-ray diffraction studies (XRD), zeta potential, Raman
spectroscopy, scanning electron microscopy (SEM) and energy dispersive analysis
of X-ray (EDX). Meanwhile, minimum inhibitory concentration (MIC), minimum
bacterial concentration (MBC), agar well diffusion and cyclic voltammetry (CV)
techniques were used for the investigation of antibacterial and electrocatalytic
behaviors of the nanocomposite, respectively. The obtained nanocomposite showed
not only enhanced electrocatalytic activity for glucose but also excellent
antibacterial activity against Escherichia coli (E. coli) and Staphylococcus
aureus (S. aureus).
PMID- 28415525
TI - Mechanical, thermal and morphological characterisation of 3D porous Pennisetum
purpureum/PLA biocomposites scaffold.
AB - The mechanical, thermal, and morphological properties of a 3D porous Pennisetum
purpureum (PP)/polylactic acid (PLA) based scaffold were investigated. In this
study, a scaffold containing P. purpureum and PLA was produced using the solvent
casting and particulate leaching method. P. purpureum fibre, also locally known
as Napier grass, is composed of 46% cellulose, 34% hemicellulose, and 20% lignin.
PLA composites with various P. purpureum contents (10%, 20%, and 30%) were
prepared and subsequently characterised. The morphologies, structures and thermal
behaviours of the prepared composite scaffolds were characterised using field
emission scanning electron microscopy (FESEM), Fourier transform infrared
spectroscopy (FTIR), and thermogravimetric analysis (TGA). The morphology was
studied using FESEM; the scaffold possessed 70-200MUm-sized pores with a high
level of interconnectivity. The moisture content and mechanical properties of the
developed porous scaffolds were further characterised. The P. purpureum/PLA
scaffold had a greater porosity factor (99%) and compression modulus (5.25MPa)
than those of the pure PLA scaffold (1.73MPa). From the results, it can be
concluded that the properties of the highly porous P. purpureum/PLA scaffold
developed in this study can be controlled and optimised. This can be used to
facilitate the construction of implantable tissue-engineered cartilage.
PMID- 28415526
TI - Effect of variable aminoalkyl chains on chemical grafting of cellulose nanofiber
and their antimicrobial activity.
AB - Recent focus on the preparation of antimicrobial surfaces using cellulose
nanofibers (CNF) has gained considerable attention. In this work,
functionalization of CNF films in 100% aqueous solution with three different
aminosilanes, including 3-aminopropyl trimethoxysilane (APMS), 2-aminoethyl 3
aminopropyl trimethoxysilane (DAMS)and 3-2-(2-aminoethylamino) ethylamino propyl
trimethoxysilane (TAMS) is reported for the fabrication of contact active
antimicrobial materials. Grafted CNF films were comprehensively characterized by
FTIR, TGA, contact angle, elemental analysis, solid-state 29Si NMR, FEG-SEM and
SEM-EDX. It was found that all the silanes were grafted on the surface of
nanofibers without any change in the morphology or fibril structure through
different grafting efficiency, depending on the aminoalkyl chain length. The
effect of variable aminoalkyl length and initial grafting concentration was
analyzed against gram-positive (Bacillus subtilis and Staphylococcus aureus) and
Gram-negative bacteria (Escherichia coli) by qualitative and quantitative
standards. The most promising results were obtained with 3-2-(2-aminoethylamino)
ethylamino propyl-trimethoxysilane at very low concentration which completely
restrict bacterial growth after 24h with Gram-positive bacteria. This study, for
the first time, established the relationship between the aminoalkyl chain length
and its corresponding antibacterial activity.
PMID- 28415527
TI - Influence of processing parameters on the macroscopic mechanical behavior of PVA
hydrogels.
AB - This paper investigates the influence of three different processing parameters on
the global mechanical behavior of PVA (Polyvinyl alcohol)/DMSO
(Dimethylsulfoxide) hydrogels: the initial concentration of PVA, the DMSO:H2O
ratio and the number of freeze/thaw cycle applied to the material. A specific
thermo-regulated testing apparatus for hydrophilic materials is presented, along
with the performed cyclic and rupture tests. The observed mechanical responses
are explained by an in-depth analysis of the cross-linking phenomenon. Using the
Neo-Hookean hyperelastic model, the experimental data is fitted and a link
between the density of macro-molecular chains in the material and its mechanical
behavior is established. Strong differences are observed and discussed.
PMID- 28415528
TI - Improved biotribological properties of PEEK by photo-induced graft polymerization
of acrylic acid.
AB - The keys of biomaterials application in artificial joints are good hydrophilicity
and wear resistance. One kind of the potential bio-implant materials is
polyetheretherketone (PEEK), which has some excellent properties such as non
toxic and good biocompatibility. However, its bioinert surface and inherent
chemical inertness hinder its application. In this study, we reported an
efficient method for improving the surface wettability and wear resistance for
PEEK, a layer of acrylic acid (AA) polymer brushes on PEEK surface was prepared
by UV-initiated graft polymerization. The effects of different grafting
parameters (UV-irradiation time/AA monomer solution concentration) on surface
characteristics were clearly investigated, and the AA-g-PEEK specimens were
examined by ATR-FTIR, static water contact angle measurements and friction tests.
Our results reveal that AA can be successfully grafted onto the PEEK surface
after UV irradiation, the water wettability and tribological properties of AA-g
PEEK are much better than untreated PEEK because that AA is a hydrophilic
monomer, the AA layer on PEEK surface can improve its bearing capacity and reduce
abrasion. This detailed understanding of the grafting parameters allows us to
accurately control the experimental products, and this method of surface
modification broadens the use of PEEK in orthopedic implants.
PMID- 28415529
TI - A sensitive voltammetric detection of pramipexole based on 1,1,3,3
tetramethyldisilazanecarbon nanotube modified electrode.
AB - A simple low-cost method is proposed to fabricate a functionalized multi-wall
carbon nanotube (MWCNT) with 1,1,3,3-tetramethyldisilazane (TMDS) molecule. The
techniques of scanning electron microscope (SEM) with electron diffraction and
energy dispersive X-ray (EDAX) analysis were applied to characterize the
functionalized TMDS-MWCNT. The results showed that a MWCNT with high
functionalization of TMDS can be obtained using this simple method. A new
nanostructure sensor was constructed based on a glassy carbon electrode modified
with TMDS-MWCNT (TMDS-MWCNT/GCE). It was found that the TMDS-MWCNT/GCE exhibits
good catalytic activity toward oxidation of pramipexole (PPX) drug, leading to a
concentration range of 0.8 to 600MUM with a detection limit of 0.2MUM at 3sigma
using the differential pulse voltammetry technique, a sensitivity of 0.084MUAMUM
1, and a correlation coefficient of 0.991. Furthermore, the TMDS-MWCNT/GCE was
used for PPX detection in tablets and human blood serum samples. The method
showed no interference from tablet excipients; hence, it can be useful and fit
for the quantification of PPX in bulk and tablet dosage forms. The proposed
method was validated successfully as applied to the quantification of the drug in
tablet dosage forms. The accuracy of detection results using the proposed method
was evaluated as excellent comparing with those obtained by the reference method.
PMID- 28415530
TI - Poly(vinylidene difluoride)/poly(tetrafluoroethylene-co-vinylpyrrolidone) blend
membranes with antifouling properties.
AB - To inhibit fouling phenomenon in membrane process, a new amphiphilic copolymer,
poly(tetrafluoroethylene-co-vinylpyrrolidone) (P(TFE-VP)), was blended with
poly(vinylidene difluoride) (PVDF) to fabricate a series of antifouling membranes
via non solvent induced phase separation (NIPS) method. The effect of copolymer
blend ratios and TFE/VP ratios on membrane properties were evaluated, and the
stability of P(TFE-VP) in PVDF membrane was studied. The membrane morphology was
controlled by adjusting polymer concentration in dope solution, such that all
membranes have similar pore size and density, as well as pure water permeability.
In evaluating the effect of TFE/VP ratios, the content of VP in dope solutions
was also adjusted to allow a fair comparison. We found that for P(TFE-VP) with a
higher VP content, adsorption of BSA on polymer film was negligible. Higher blend
ratios of this copolymer resulted in higher surface VP content and better
hydrophilicity, but antifouling performance ceased to improve when blend ratio
was larger than 1:9 (copolymer:PVDF). Meanwhile, a lower VP content in copolymer
resulted in inferior hydrophilicity and severe fouling of the blend membranes. It
was also proved that comparing with PVP homopolymer, P(TFE-VP) had satisfying
stability inside PVDF membrane.
PMID- 28415531
TI - New synthesis of poly ortho-methoxyaniline nanostructures and its application to
construct modified multi-wall carbon nanotube/graphite paste electrode for
simultaneous determination of uric acid and folic acid.
AB - Uric acid (UA) and folic acid (FA) are compounds of biomedical interest. In
humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5
25% of humans, impaired renal (kidney) excretion leads to hyperuricemia. Folate
is another form folic acid of which is known as, is one of the B vitamins. It is
used as a supplement by women to prevent neural tube defects developing during
pregnancy. Polyortho-methoxyaniline nanostructures (POMANS) was synthesized with
a new two phase (organic-water) synthesis method. The POMANS was characterized
using transmission electron microscopy (TEM) and Fourier transform IR (FTIR).
This polymer was used to construct a modified multi-wall carbon nanotube,
graphite paste electrode (POMANS-MWCNT/GPE). Linear sweep voltammograms (LSV),
cyclic voltammetry (CV) and chronoamperometry were used to investigate the
suitability of polyortho-methoxyaniline with multi-wall carbon nanotubes paste
electrode as a modifier for the electrocatalytic oxidation of UA and FA in
aqueous solutions with various pHs. The results showed that POMANS-MWCNT/GPE had
high anodic peak currents for the electrooxidation of UA and FA in pH6.0.Under
the optimized conditions, The catalytic peak currents obtained, was linearly
dependent on the UA and FA concentrations in the range of 0.6-52 and 0.5-68MUM
with two segments and the detection limits 0.157 and 0.113MUM for UA and FA were,
respectively. Finally, the proposed method was also examined as a sensitive,
simple and inexpensive electrochemical sensor for the simultaneous determination
of UA and FA in real samples such as urine and serum.
PMID- 28415532
TI - Preparation of micro-porous bioceramic containing silicon-substituted
hydroxyapatite and beta-tricalcium phosphate.
AB - Dimensional instability caused by sintering shrinkage is an inevitable drawback
for conventional processing of hydroxyapatite (HA). A new preparation method for
biphasic calcium phosphates was developed to increase micro pores and
biodegradation without significant dimensional change. Powder pressed HA discs,
under 100MPa, were immersed in a colloidal mixture of tetraethoxysilane (TEOS)
and ammonium hydroxide for 10min, followed by drying, and then were sintered at
900 degrees C, 1050 degrees C, and 1200 degrees C, respectively. Comparing with
pure HA discs, the newly prepared product sintered up to 1200 degrees C contained
silicon substituted HA, beta-tricalcium phosphate, and calcium silicate with
better micro-porosity, high specific surface area, less sintering shrinkage and
the strength maintained. The cytocompatibility test demonstrated a better
viability for D1 mice stem cells cultured on TEOS treated HA for 14days compared
to the pure HA. This simple TEOS sol-gel pretreatment has the potential to be
applied to any existing manufacturing process of HA scaffold for better control
of sintering shrinkage, create micropores, and increase biodegradation.
PMID- 28415533
TI - Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS
hybrid composite for bone tissue engineering applications.
AB - The bioactivity and mechanical properties of hybrid composites of hydroxyapatite
(HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are
investigated, first time, for regeneration and repair of the bone tissues. HA is
synthesized to obtain the spherically shaped nanoparticles in the size range of
60+/-20nm. Various concentrations of HA ranging from 1 to 30wt% are dispersed in
TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and
interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron
microscope shows the uniform dispersion of HA<=10wt% in TOPAS and at higher
concentrations >10wt%, agglomeration occurs in the hybrid composites. Tunable
mechanical properties are achieved as the compressive modulus and strength are
increased around 140% from 6.4 to 15.3MPa and 185% from 0.26 to 0.74MPa,
respectively. Such increase in the mechanical properties of TOPAS is attributed
to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing
to better dispersion and interfacial interactions. In comparison to neat TOPAS,
hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation
significantly. The cell density and proliferation of TOPAS/HA hybrid composites
is enhanced 9 and 3 folds, respectively, after 1day culturing in preosteoblasts
cells. Moreover, the morphology of cells changed from spherical to flattened
spread morphology demonstrating clearly the migration of the cells for the
formation of interconnected cellular network. Additionally, very few dead cells
are found in hybrid composites showing their cytocompatibility. Overall, the
hybrid composites of TOPAS/HA exhibited superior strength and stiffness along
with enhanced cytocompatibility for bone tissue engineering applications.
PMID- 28415534
TI - Influence of Si substitution on the reactivity of alpha-tricalcium phosphate.
AB - Silicon substituted calcium phosphates have been widely studied over the last ten
years due to their enhanced osteogenic properties. Notwithstanding, the role of
silicon on alpha-TCP reactivity is not clear yet. Therefore, the aim of this work
was to evaluate the reactivity and the properties of Si-alpha-TCP in comparison
to alpha-TCP. Precursor powders have similar properties regarding purity,
particle size distribution and specific surface area, which allowed a better
comparison of the Si effects on their reactivity and cements properties. Both Si
alpha-TCP and alpha-TCP hydrolyzed to a calcium-deficient hydroxyapatite when
mixed with water but their conversion rates were different. Si-alpha-TCP
exhibited a slower setting rate than alpha-TCP, i.e. kSSA for Si-TCP (0.021g.m
2.h-1) was almost four times lower than for alpha-TCP (0.072g.m-2.h-1). On the
other hand, the compressive strength of the CPC resulting from fully reacted Si
alpha-TCP was significantly higher (12.80+/-0.38MPa) than that of alpha-TCP
(11.44+/-0.54MPa), due to the smaller size of the entangled precipitated apatite
crystals.
PMID- 28415535
TI - Study on montmorillonite/insulin/TiO2 hybrid nanocomposite as a new oral drug
delivery system.
AB - This study was conducted in two main stages. In the first stage, drug-loaded
montmorillonite nanocomposites were prepared by intercalation of insulin into the
montmorillonite layers in acidic deionized (DI) water. In the second stage, to
increase the release of insulin from the prepared nanocomposites they were coated
with TiO2, an inorganic porous coating, by using titanium (IV) butoxide, as
precursor. The prepared nanocomposites were characterized by FT-IR, XRD, FE-SEM,
BET, DLS and Zeta potential analysis. After investigating the release behaviour
of the nanocomposites by UV-Vis absorbance technique, the results revealed that
incorporation of porous TiO2 coating increased the drug entrapment noticeably,
and decreased the amount of drug release, so that nanocomposites without and with
TiO2 coating released the drug after 60min and 22h in pH7.4, respectively. These
results could be used in converting the insulin utilization from injection to
oral.
PMID- 28415536
TI - Template-etching route to construct uniform rattle-type Fe3O4@SiO2 hollow
microspheres as drug carrier.
AB - Template-etching strategy was put forward to synthesize rattle-type magnetic
silica (Fe3O4@SiO2) hollow microspheres in a controlled way. During the
experiment, monodisperse Fe2O3 microspheres were fabricated as physical template
to generate uniform Fe2O3@SiO2 with controlled shell thicknesses through sol-gel
method, and the subsequent Fe2O3 template etching process created variable space
between Fe2O3 core and SiO2 shell, and the final calcination process transformed
rattle-type Fe2O3@SiO2 hollow microspheres into corresponding Fe3O4@SiO2 product
in hydrogen/nitrogen atmosphere. Compared with traditional physical template,
here template-etching synthesis of rattle-type hollow microspheres saved the
insertion of middle shells and their removal, which simplified the synthesis
process with controllable core size and shell thickness. The rattle-type
Fe3O4@SiO2 hollow microspheres as drug carrier show efficient doxorubicin (DOX)
loading, and the release rate of DOX loaded the rattle-type Fe3O4@SiO2 hollow
microspheres exhibit a surprising shell-thickness-dependent and a pH responsive
drug release features. Additionally, MTT assays in HeLa cells demonstrated that
the Fe3O4@SiO2 nanocarriers were non-toxic even at the concentration of 250ugmL-1
for 48h. Thus, our results revealed that the Fe3O4@SiO2-DOX could play an
important role in the development of intracellular delivery nanodevices for
cancer therapy.
PMID- 28415537
TI - Potassium-doped mesoporous bioactive glass: Synthesis, characterization and
evaluation of biomedical properties.
AB - A bifunctional mesoporous bioactive glass (MBG) with composition
(49SiO2.20CaO.20Na2O.7K2O.4P2O5 mol%) was synthesized by a facile sol-gel method,
using polyethylene glycol (PEG 6000) as a soft template. The structure,
morphology (spherical with approximate size 1MUm) and composition of MBG were
determined by fourier transform infrared spectroscopy, the scanning electron
microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX), respectively.
The surface area (189.53m2g-1 with the pore size of 21nm) of MBG was measured by
Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) analysis. The
formation of hydroxyapatite (HAp) layer on the glass surface upon immersion in
simulated body fluid (SBF) was monitored through X-ray diffraction (XRD) which
indicates enhanced bioactivity as compared to previous studies. The animals
study, protein adsorption ability, and cytotoxicity investigations show no tissue
damage, good biomedical properties and no encumbrance with cell cycle (even at a
concentration of 80MUg/mL). Moreover, the cell proliferation analysis reveals the
non-toxic property of MBG at a concentration of 20MUg/mL. Notably, a cumulative
drug (ciprofloxacin, an antibiotic) release of 75% was observed for first 48h and
the further release of 90% was observed over a period of two weeks. The
synthesized MBG also shows osteoblast activity and bone mineralization as
revealed by alkaline phosphatase activity (ALP) and osteocalcin formation.
PMID- 28415538
TI - Fabrication of polypropylene/silver nanocomposites for biocidal applications.
AB - This paper presents a study on biocidal effect of polymer nanocomposite films of
gamma irradiated polypropylene (PP) and silver nanoparticles. The modified
polypropylene was obtained from isotactic polypropylene (iPP) in pellets form by
irradiation with gamma rays in the presence of acetylene. A new morphology with
long chain branching of PP and distinct rheology is obtained by this process. The
blend of 50/50wt% neat PP and PP modified by gamma radiation were further mixed
using a twin screw extruder. The AgNPs were infused into this polymer blend at
different concentrations of: 0.1%; 0.25%; 0.5%; 1.0%; 1.0% (PVP), 2.0% and 4.0%
by wt%. These polymer nanocomposites were characterized by Raman spectroscopy,
scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS),
thermogravimetric analysis (TG), differential scanning calorimetry (DSC), X-ray
diffraction (XRD), transmission electron microscopy (TEM), cytotoxicity test and
Kirby-Bauer disk diffusion techniques. The bactericidal effect of Pseudomonas
aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) were assessed in
detail.
PMID- 28415539
TI - In vitro cytotoxicity evaluation of nano-carbon particles with different sp2/sp3
ratios.
AB - Graphitization occurs during the long-term service of a diamond-like carbon (DLC)
modified artificial joint. Then, DLC wear debris, which are carbon particles with
different sp2/sp3 ratios and sizes ranging from the nano- to micro-meter scale
produced. In this paper, to promote the application of DLC coating for artificial
joint modification, the cytotoxicity of DLC debris (nano-carbon particles, NCs)
with different sp2/sp3 ratios was studied. The microstructure and physical
characteristics of NCs with different sp2/sp3 ratios were investigated by Raman
spectroscopy, X-ray photoelectron spectroscopy (XPS), Transmission Electron
Microscope (TEM) and Dynamic Light Scattering (DLS). Meanwhile, osteoblasts and
macrophages were applied to characterize the cytotoxicity of the NCs. In vitro
cytotoxicity assay results indicated that cells incubated with NCs of different
sp2/sp3 ratios had greater osteogenic capacity, and these particles caused a
weaker immune response in comparison with CoCrMo particles. Taken together, the
results indicated that NCs with different sp2/sp3 ratios presented a good
cytocompatibility than CoCrMo particles. But no significant differences were
observed among NCs with different sp2/sp3 ratios. The better cytocompatibility of
NCs is mainly attributable to their surface charge.
PMID- 28415540
TI - Biocompatible magnetite nanoparticles synthesized by one-pot reaction with a cell
membrane mimetic copolymer.
AB - In this paper, a series of random copolymers poly(methacrylic acid -co-2
methacryloyloxyethyl phosphorylcholine) P(MAA-co-MPC) were synthesized firstly
via RAFT living polymerization. The P(MAA-co-MPC) copolymer side chains bear cell
membrane phosphorylcholine zwitterions to endow biocompatibility and carboxylic
groups to confer coordination with metal ions. Thus, the copolymer was adopted to
modify Fe3O4 nanoparticle by a one-pot coprecipitation approach. The effects of
the copolymer composition as well as the ratio between the copolymers and iron
ions on the performances of the magnetite nanoparticles were researched. The
diameters of the nanoparticles could be easily tuned by changing the initial
copolymer amount. Moreover, a long-term colloidal stability of magnetite
particles was obtained after P(MAA-co-MPC) modification. Biocompatibility of the
P(MAA-co-MPC) copolymer coated magnetite nanoparticles was investigated by
protein adsorption, in vitro cytotoxicity and cell uptake studies. It was found
that the copolymer content of magnetite nanoparticles correlates with its
biocompatibility. Excellent biocompatibility could be obtained when the content
of the copolymer in the composite nanoparticles reached to 54%.
PMID- 28415541
TI - Synthesis, characterization of CaF2 doped silicate glass-ceramics.
AB - This paper reports the fabrication and characterization of silicate glass
ceramics doped with (0-12mol%) CaF2. TGA-DSC analysis was carried out to
determine the crystallization temperature and stability of glass measured by two
glass parameters; Hruby parameter KH=(Tx-Tg)/(TL-Tx) and Weinberg parameter
KW=(Tc-Tg)/TL. It was found that with CaF2 doping improved sinterability at low
temperature and provided stability to the glass. The XRD pattern exhibits a
single phase of combeite and doping of CaF2 cause increase in crystallite size.
Microstructure of samples was also improved with CaF2 addition, pores were
significantly reduced. After 15days immersion in simulated body fluid all samples
developed apatite layer onto its surface. Hence, the addition of CaF2 provided
bioactive glass-ceramic material having a low processing temperature.
PMID- 28415542
TI - Bladder smooth muscle cells on electrospun poly(epsilon-caprolactone)/poly(l
lactic acid) scaffold promote bladder regeneration in a canine model.
AB - Engineering of urinary bladder has been the focus of numerous studies in recent
decade. Novel biomaterials, innovative fabrication methods and various
modification processes of scaffolds are the critical issues to find supportive
matrices. Supportive characteristics of electrospun PCL/PLLA nano-scaffold for
bladder augmentation in canine model and the role of bladder cells in
regeneration process were appraised. Electrospun PCL/PLLA was fabricated by co
electrospinning of PCL and PLLA. Bladder cells were isolated and transduced with
lentiviral particles encoding eGFP and JRed proteins. Electrospun PCL/PLLA was
seeded with different bladder cells individually or in co-culture condition. Cell
free and cell-seeded electrospun PCL/PLLA scaffolds (10cm2) were surgically
implanted in bladders of eight female dogs for three months. To evaluate bladder
regeneration, the dogs were sacrificed and their bladders were examined
macroscopically and microscopically for presence of tracking proteins, expression
of cell-specific markers and histological attributes of regenerated tissues. All
animals survived the experiment with no complication. In smooth muscle
transplanted group complete regeneration and covering of scaffold were observed.
Other groups revealed partial regeneration. A well-developed layer of urothelium
was formed in all groups in regenerated parts. Smooth muscle transplanted group
showed the most developed muscle layer. Regenerated tissue demonstrated typical
expression of cell-specific markers. No expression of eGFP and JRed was observed.
Electrospun PCL/PLLA scaffold with proper handling, suture retention, nano-sized
surface features, maintenance of normal phenotype of cells and minimal adverse
effects in body can be a supportive substrate for bladder wall regeneration when
seeded with bladder smooth muscle cells.
PMID- 28415543
TI - Facile synthesis of a silver nanoparticles/polypyrrole nanocomposite for non
enzymatic glucose determination.
AB - The present work describes the synthesis of a new conductive nanocomposite based
on polypyrrole (PPy) and silver nanoparticles (PPy-AgNP) based on a facile
reverse microemulsion method and its application as a non-enzymatic
electrochemical sensor for glucose detection. Focusing on the best sensor
performance, all experimental parameters used in the synthesis of nanocomposite
were optimized based on its electrochemical response for glucose.
Characterization of the optimized material by FT-IR, cyclic voltammetry, and DRX
measurements and TEM images showed good monodispersion of semispherical Ag
nanoparticles capped by PPy structure, with size average of 12+/-5nm. Under the
best analytical conditions, the proposed sensor exhibited glucose response in
linear dynamic range of 25 to 2500MUmolL-1, with limit of detection of 3.6MUmolL
1. Recovery studies with human saliva samples varying from 99 to 105% revealed
the accuracy and feasibility of a non-enzymatic electrochemical sensor for
glucose determination by easy construction and low-cost.
PMID- 28415545
TI - Engineering bone regeneration with novel cell-laden hydrogel microfiber
injectable calcium phosphate scaffold.
AB - Cell-based tissue engineering is promising to create living functional tissues
for bone regeneration. The implanted cells should be evenly distributed in the
scaffold, be fast-released to the defect and maintain high viability in order to
actively participate in the regenerative process. Herein, we report an injectable
calcium phosphate cement (CPC) scaffold containing cell-encapsulating hydrogel
microfibers with desirable degradability that could deliver cells in a timely
manner and maintain cell viability. Microfibers were synthesized using partially
oxidized alginate with various concentrations (0-0.8%) of fibrinogen to optimize
the degradation rate of the alginate-fibrin microfibers (Alg-Fb MF). A fibrin
concentration of 0.4% in Alg-Fb MF resulted in the greatest enhancement of cell
migration, release and proliferation. Interestingly, a significant amount of cell
cell contact along the long-axis of the microfibers was established in Alg-0.4%Fb
MF as early as day 2. The injectable tissue engineered construct for bone
reconstruct was fabricated by mixing the fast-degradable Alg-0.4%Fb MF with CPC
paste at 1:1 volume ratio. In vitro study showed that cells re-collected from the
construct maintained good viability and osteogenic potentials. In vivo study
demonstrated that the hBMSC-encapsulated CPC-MF tissue engineered construct
displayed a robust capacity for bone regeneration. At 12weeks after implantation,
osseous bridge in the rat mandibular defect was observed in CPC-MF-hBMSCs group
with a new bone area fraction of (42.1+/-7.8) % in the defects, which was >3-fold
that of the control group. The novel tissue-engineered construct presents an
excellent prospect for a wide range of dental, craniofacial and orthopedic
applications.
PMID- 28415544
TI - beta-pyrophosphate: A potential biomaterial for dental applications.
AB - Tooth hypersensitivity is a growing problem affecting both the young and ageing
population worldwide. Since an effective and permanent solution is not yet
available, we propose a new methodology for the restoration of dental enamel
using femtosecond lasers and novel calcium phosphate biomaterials. During this
procedure the irradiated mineral transforms into a densified layer of acid
resistant iron doped beta-pyrophosphate, bonded with the surface of eroded
enamel. Our aim therefore is to evaluate this densified mineral as a potential
replacement material for dental hard tissue. To this end, we have tested the
hardness of beta-pyrophosphate pellets (sintered at 1000 degrees C) and its
mineral precursor (brushite), the wear rate during simulated tooth-brushing
trials and the cytocompatibility of these minerals in powder form. It was found
that the hardness of the beta-pyrophosphate pellets is comparable with that of
dental enamel and significantly higher than dentine while, the brushing trials
prove that the wear rate of beta-pyrophosphate is much slower than that of
natural enamel. Finally, cytotoxicity and genotoxicity tests suggest that iron
doped beta-pyrophosphate is cytocompatible and therefore could be used in dental
applications. Taken together and with the previously reported results on laser
irradiation of these materials we conclude that iron doped beta-pyrophosphate may
be a promising material for restoring acid eroded and worn enamel.
PMID- 28415546
TI - Effect of nano/micro-Ag compound particles on the bio-corrosion, antibacterial
properties and cell biocompatibility of Ti-Ag alloys.
AB - In this research, Ti-Ag alloys were prepared by powder metallurgy, casting and
heat treatment method in order to investigate the effect of Ag compound particles
on the bio-corrosion, the antibacterial property and the cell biocompatibility.
Ti-Ag alloys with different sizes of Ag or Ag-compounds particles were
successfully prepared: small amount of submicro-scale (100nm) Ti2Ag precipitates
with solid solution state of Ag, large amount of nano-scale (20-30nm) Ti2Ag
precipitates with small amount of solid solution state of Ag and micro-scale
lamellar Ti2Ag phases, and complete solid solution state of Ag. The mechanical
tests indicated that both nano/micro-scale Ti2Ag phases had a strong dispersion
strengthening ability and Ag had a high solid solution strengthening ability.
Electrochemical results shown the Ag content and the size of Ag particles had a
limited influence on the bio-corrosion resistance although nano-scale Ti2Ag
precipitates slightly improved corrosion resistance. It was demonstrated that the
nano Ag compounds precipitates have a significant influence on the antibacterial
properties of Ti-Ag alloys but no effect on the cell biocompatibility. It was
thought that both Ag ions release and Ti2Ag precipitates contributed to the
antibacterial ability, in which nano-scale and homogeneously distributed Ti2Ag
phases would play a key role in antibacterial process.
PMID- 28415547
TI - Effect of polymer degradation on prolonged release of paclitaxel from
filomicelles of polylactide/poly(ethylene glycol) block copolymers.
AB - Paclitaxel is one of the most efficient anticancer agents, but the conventional
dosage formulations cause many side effects. PLA-PEG filomicelles are promising
carriers of paclitaxel because high loading capacity and long term release can be
achieved. Slow release of cytostatic drugs is very advantageous due to prolonged
exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this
study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for
prolonged delivery of paclitaxel. Paclitaxel is encapsulated in PLLA-PEG
filomicelles and PDLLA-PEG spherical micelles. Drug release was studied in PBS at
37 degrees C at various pH values to elucidate the influence of polymer
degradation on drug release. NMR, GPC and HPLC were used to follow polymer
degradation and drug release. The release of paclitaxel is strongly dependent on
the degradation of micelles. A biphasic drug release profile is observed for both
PLLA-PEG and PDLLA-PEG micelles: slow release in the first phase and faster
release in the second phase. Degradation is faster at acidic pH than at pH7.4,
and PLLA-PEG filomicelles degrade less rapidly than PDLLA-PEG spherical micelles,
leading to various rates of drug release. The correlation between degradation and
drug release is very helpful for the development of novel drug carriers with
tailored properties. Importantly, the cytotoxic activity of PLLA-PEG filomicelles
was evidenced, thus showing their potential as carrier of antitumor drugs.
PMID- 28415548
TI - In vitro evaluation of Ag-containing calcium phosphates: Effectiveness of Ag
incorporated beta-tricalcium phosphate.
AB - Development of bioceramics with antibacterial activity and without cytotoxicity
would be beneficial for preventing infection associated with implants. This study
aimed to capitalize on the antibacterial properties of silver (Ag) incorporated
in or coexisting in metallic form with calcium phosphates (CaPs). The in vitro
dissolution behavior, antibacterial activity, and cytotoxicity of Ag-containing
CaPs with different phase fractions of hydroxyapatite (HA) and beta-tricalcium
phosphate (beta-TCP) were evaluated. The antibacterial activity of Ag-containing
CaPs depended on the main phase of CaP, the chemical state of Ag, and the amount
of incorporated Ag. Superior antibacterial activity was obtained from sustained
release of Ag ions through continuous dissolution of Ag-incorporated beta-TCP
compared to that obtained for HA coexisting with metallic Ag particles. Ag
containing CaPs did not exhibit any toxic effect on V79 fibroblasts. Thus, these
results demonstrated the effectiveness of Ag-incorporated beta-TCP in preventing
infection, with respect to long-term applications.
PMID- 28415549
TI - The precursors effects on biomimetic hydroxyapatite ceramic powders.
AB - In this study, effects of the starting material on chemical, physical, and
biological properties of biomimetic hydroxyapatite ceramic powders (BHA) were
investigated. Characterization and chemical analysis of BHA powders were
performed by using XRD, FT-IR, and ICP-AES. Microstructural features such as size
and morphology of the resulting BHA powders were characterized by using BET, nano
particle sizer, pycnometer, and SEM. Additionally, biological properties of the
BHA ceramic powders were also investigated by using water-soluble tetrazolium
salts test (WST-1). According to the chemical analysis of BHA ceramic powders,
chemical structures of ceramics which are prepared under different conditions and
by using different starting materials show differences. Ceramic powders which are
produced at 80 degrees C are mainly composed of hydroxyapatite, dental
hydroxyapatite (contain Na and Mg elements in addition to Ca), and calcium
phosphate sulfide. However, these structures are altered at high temperatures
such as 900 degrees C depending on the features of starting materials and form
various calcium phosphate ceramics and/or their mixtures such as Na-Mg
hydroxyapatite, hydroxyapatite, Mg-Whitlockit, and chloroapatite. In vitro
cytotoxicity studies showed that amorphous ceramics produced at 80 degrees C and
ceramics containing chloroapatite structure as main or secondary phases were
found to be extremely cytotoxic. Furthermore, cell culture studies showed that
highly crystalline pure hydroxyapatite structures were extremely cytotoxic due to
their high crystallinity values. Consequently, the current study indicates that
the selection of starting materials which can be used in the production of
calcium phosphate ceramics is very important. It is possible to produce calcium
phosphate ceramics which have sufficient biocompatibility at physiological pH
values and by using appropriate starting materials.
PMID- 28415550
TI - High impact of in situ dextran coating on biocompatibility, stability and
magnetic properties of iron oxide nanoparticles.
AB - Biocompatible ferrofluids based on dextran coated iron oxide nanoparticles were
fabricated by conventional co-precipitation method. The experimental results show
that the presence of dextran in reaction medium not only causes to the appearance
of superparamagnetic behavior but also results in significant suppression in
saturation magnetization of dextran coated samples. These results can be
attributed to size reduction originated from the role of dextran as a surfactant.
Moreover, weight ratio of dextran to magnetic nanoparticles has a remarkable
influence on size and magnetic properties of nanoparticles, so that the sample
prepared with a higher weight ratio of dextran to nanoparticles has the smaller
size and saturation magnetization compare with the other samples. In addition,
the ferrofluids containing such nanoparticles have an excellent stability at
physiological pH for several months. Furthermore, the biocompatibility studies
reveal that surface modification of nanoparticles by dextran dramatically
decreases the cytotoxicity of bare nanoparticles and consequently improves their
potential application for diagnostic and therapeutic purposes.
PMID- 28415551
TI - A biodegradable AZ91 magnesium alloy coated with a thin nanostructured
hydroxyapatite for improving the corrosion resistance.
AB - The main aim of this study was to investigate the properties of an AZ91 alloy
coated with nanostructured hydroxyapatite (HA) prepared by radio frequency (RF)
magnetron sputtering. The bioactivity and biomineralization of the AZ91 magnesium
alloy coated with HA were investigated in simulated body fluid (SBF) via an in
vitro test. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR)
spectroscopy, and X-ray diffraction (XRD) analyses were performed. The samples
were immersed in SBF to study the ability of the surface to promote the formation
of an apatite layer as well as corrosion resistance and mass change of the HA
coated AZ91 alloy. Electrochemical tests were performed to estimate the corrosion
behaviour of HA-coated and uncoated samples. The results revealed the capability
of the HA coating to significantly improve the corrosion resistance of the
uncoated AZ91 alloy.
PMID- 28415552
TI - In vitro and in vivo characterization of anodised zirconium as a potential
material for biomedical applications.
AB - In vitro studies offer the insights for the understanding of the mechanisms at
the tissue-implant interface that will provide an effective functioning in vivo.
The good biocompatibility of zirconium makes a good candidate for biomedical
applications and the attractive in vivo performance is mainly due to the presence
of a protective oxide layer. The aim of this study is to evaluate by in vitro and
in vivo approach, the influence of surface modification achieved by anodisation
at 30 and 60V on zirconium implants on the first steps of the osseointegration
process. In this study cell attachment, proliferation and morphology of mouse
myoblast C2C12-GFP and in mouse osteoprogenitor MC3T3-E1 cells was evaluated.
Also, together with the immune system response, osteoclast differentiation and
morphology with RAW 264.7 murine cell line were analysed. It was found that
anodisation treatment at 60V enhanced cell spreading and the osteoblastic and
osteoclastic cells morphology, showing a strong dependence on the surface
characteristics. In vivo tests were performed in a rat femur osteotomy model.
Dynamical and static histological and histomorphometric analyses were developed
15 and 30days after surgery. Newly formed bone around Zr60V implants showed a
continuous newly compact and homogeneous bone just 15 after surgery, as judged by
the enhanced thickness and mineralization rate. The results indicate that
anodising treatment at 60V could be an effective improvement in the
osseointegration of zirconium by stimulating adhesion, proliferation, morphology,
new bone thickness and bone mineral apposition, making zirconium an emerging
candidate material for biomedical applications.
PMID- 28415553
TI - Promising silicones modified with cationic biocides for the development of
antimicrobial medical devices.
AB - We have tested silicones containing 2% or 5% of the cationic biocides
polyhexamethylene guanidine dodecylbenzenesulfonate (PHMG-DBS), 1-octyl-3
methylimidazolium tetrafluoroborate (OMIM-BF4) or 1-dodecyl-3-methylimidazolium
tetrafluoroborate (DMIM-BF4) against the major relevant bacterial and yeast
species in health care-associated infections (HCAI). Study conducted according to
the international standard ISO 22196 revealed that silicones containing 2% or 5%
DMIM-BF4 or 5% PHMG-DBS presented the highest antimicrobial activity, leading to
a logarithmic growth reduction of 3.03 to 6.46 and 3.65 to 4.85 depending on the
bacterial or fungal species. Heat-pretreated silicones containing 2% DMIM-BF4
kept a high activity, with at least a 3-log reduction in bacterial growth, except
against P. aeruginosa where there was only a 1.1-log reduction. After 33days, the
release ratio of cationic biocide from silicone films containing 5% of DMIM-BF4
was found to be 5.6% in pure water and 1.9% in physiological saline solution,
respectively. No leaching of PHMG-DBS polymeric biocide was detected under the
same conditions. These results demonstrate unambiguously that silicones
containing 2% DMIM-BF4 or 5% PHMG-DBS present high antimicrobial activity, as
well as high leaching resistance and therefore may be good candidates for the
development of safer medical devices.
PMID- 28415554
TI - Phytosynthesis of silver nanoparticles using aqueous leaf extracts of Lippia
citriodora: Antimicrobial, larvicidal and photocatalytic evaluations.
AB - Nanoscience and nanotechnology represent new and enabling platforms that promise
to provide broad range of novel and improved technologies for environmental,
biological and other scientific applications. This study reports the synthesis of
silver nanoparticles mediated by aqueous leaf extract of Lippia citriodora at two
different temperatures of 50 degrees C and 90 degrees C. The synthesis of
colloidal silver nanoparticles (AgNPs) was monitored by the use of UV-visible
spectroscopy at different temperatures and time intervals. The surface plasmon
bands (SPBs) showed peaks between 417 and 421nm at 90 degrees C and around 430nm
at 50 degrees C, indicating a red shift at lower temperature. Fourier transform
infrared (FTIR) analysis of the nanoparticles showed the presence of similar
peaks found in the spectra of the plant extract. The size of the AgNPs was
confirmed by transmission electron microscopy (TEM) which indicated an average
size of 23.8nm (90 degrees C) and 25nm (50 degrees C). The nanoparticles showed
better antimicrobial activities when compared to the crude plant extract against
several screened pathogens: Gram negative (Escherichia coli, and Salmonella
typhi) and Gram positive (Bacillus subtilis and Staphylococcus aureus) strains
and a fungi organism; Candida albicans. In addition, the AgNPs showed good
larvicidal efficacy against early 4th instar of Culex quinquefasciatus (a vector
of lymphatic filariasis). Finally, the nanoparticles exhibited photocatalytic
properties on an industrial waste pollutant, methylene blue.
PMID- 28415555
TI - Yb3+,Er3+,Eu3+-codoped YVO4 material for bioimaging with dual mode excitation.
AB - We propose an efficient bioimaging strategy using Yb3+,Er3+,Eu3+-triplet doped
YVO4 nanoparticles which were synthesized with polymer as a template. The
obtained particles possess nanoscale, uniform, and flexible excitation. The
effect of Eu3+ ions on the luminescence properties of YVO4:Yb3+,Er3+,Eu3+ was
investigated. The upconversion mechanism of the prepared material was also
discussed. The structure and optical properties of the prepared material were
characterized by using X-ray diffraction (XRD), Fourier-transform IR spectroscopy
(FTIR), scanning electron microscopy (SEM), Transmission electron microscopy
(TEM) upconversion and photoluminescence spectra. The Commission International de
I'Eclairage (CIE) chromaticity coordinates was investigated to confirm the
performance of color luminescent emission. The prepared YVO4:Yb3+,Er3+,Eu3+
nanoparticles could be easily dispersed in water by surface modification with
cysteine (Cys) and glutathione (GSH). The aqueous dispersion of the modified
YVO4:Yb3+,Er3+,Eu3+ exhibits bright upconversion and downconversion luminescence
and has been applied for bioimaging of HeLa cells. Our developed material with
dual excitation offers a promising advance in bioimaging.
PMID- 28415556
TI - Construction of Zn-incorporated multilayer films to promote osteoblasts growth
and reduce bacterial adhesion.
AB - To improve the biological performance of titanium substrates, a bioactive
multilayered structure of chitosan/gelatin pair, containing zinc ions, was
constructed via a layer-by-layer self-assembly technique. The successful
preparation of zinc ions incorporated multilayer films was demonstrated by
scanning electron microscopy, X-ray photoelectron spectroscopy, and contact angle
measurements, respectively. The biological behaviors of osteoblasts adhered to
modified Ti substrates were investigated in vitro via cytoskeleton observation,
cell viability measurement, and alkaline phosphatase activity assay. The
cytocompatibility evaluation verified that the present system was capable of
promoting the growth of osteoblasts. In addition, Gram-positive (Staphylococcus
aureus) and Gram-negative (Escherichia coli) bacteria were used to evaluate
antibacterial property of modified Ti substrates. Bacterial adhesion and
viability assay confirmed that Zn-loaded multilayer films were able to inhibit
the adhesion and growth of bacteria. The approach presented here affords an
alternative to reduce bacterial infection and promote osteoblast growth for
titanium-based implants.
PMID- 28415557
TI - Long non-coding RNA CTA sensitizes osteosarcoma cells to doxorubicin through
inhibition of autophagy.
AB - Recently, several long non-coding RNAs (lncRNAs) have been implicated in
osteosarcoma (OS). However, the regulatory roles of lncRNAs in chemotherapy
resistance of OS still remain unclear. This study aimed to screen a novel lncRNA
that contributes to chemotherapeutic resistance of OS, and to explore the
underlying mechanisms. Our data showed that lncRNA CTA was markedly downregulated
in OS tissues compared to their matched non-tumor tissues, and low expression of
lncRNA CTA was significantly associated with the advanced clinical stage and
tumor size. In addition, OS patients with low lncRNA CTA levels showed a worse
prognosis when compared with those with high expression of lncRNA CTA.
Furthermore, we report that lncRNA CTA has an inverse relationship with miR-210
expression in OS tissues. LncRNA CTA could be activated by doxorubicin (DOX), and
could promote OS cell apoptosis by competitively binding miR-210, while inhibit
cell autophagy. On the other hand, lncRNA CTA was downregulated in DOX-resistant
OS cells. Overexpression of lncRNA CTA reduced autophagy and subsequently
overcame DOX resistance of OS in vitro and in vivo. Therefore, we demonstrate
that lncRNA CTA is an essential regulator in DOX-induced OS cell apoptosis, and
the lncRNA CTA-miR-210 axis plays an important role in reducing OS
chemoresistance.
PMID- 28415558
TI - Family with sequence similarity 13C (FAM13C) overexpression is an independent
prognostic marker in prostate cancer.
AB - FAM13C, a gene with unknown function is included in several mRNA signatures for
prostate cancer aggressiveness. To understand the impact of FAM13C on prognosis
and its relationship to molecularly defined subsets, we analyzed FAM13C
expression by immunohistochemistry on a tissue microarray containing 12,400
prostate cancer specimens. Results were compared to phenotype, ERG status,
genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. FAM13C was
detectable in cell nuclei of cancerous and non-neoplastic prostate cells. 67.5%
of 9,633 interpretable cancers showed FAM13C expression: strong in 28.3%,
moderate in 24.6% and weak in 14.6%. Strong FAM13C expression was linked to
advanced pT stage, high Gleason grade, positive lymph node status, and early
biochemical recurrence (p < 0.0001 each). FAM13C expression was associated with
TMPRSS2:ERG fusions. It was present in 85% of ERG positive but in only 54% of ERG
negative cancers (p < 0.0001), and in 91.1% of PTEN deleted but in only 69.2% of
PTEN non-deleted cancers (p < 0.0001). The prognostic role of FAM13C expression
was independent of classical and quantitative Gleason grade, pT stage, pN stage,
surgical margin status and preoperative PSA. In conclusion, the results of our
study demonstrate that expression of FAM13C is an independent prognostic marker
in prostate cancer. Finding FAM13C also in non-neoplastic prostate tissues
highlights the importance of properly selecting cancer-rich areas for RNA-based
FAM13C expression analysis.
PMID- 28415559
TI - Transcriptome analysis reveals differentially expressed lncRNAs between oral
squamous cell carcinoma and healthy oral mucosa.
AB - Oral cavity and oropharyngeal squamous cell carcinoma (OSCC) is a major cancer
type in the head and neck region. To better understand the roles long non-coding
RNA (lncRNA) play in OSCC carcinogenesis, we compared the expression levels of
3,054 probe sets for lncRNAs between 167 OSCCs and 45 healthy oral mucosa using
an Affymetrix HG U133 plus 2.0 array dataset. We found 658 lncRNA transcripts
(790 probe sets) to be significantly differentially expressed using a criteria of
FDR < 0.01, with 36 of them (39 probe sets) showing more than a 2-fold change. We
further validated the top differentially expressed lncRNAs in three independent
datasets from Gene Expression Omnibus (GEO) repository: GSE42743, GSE9844, and
GSE6791. Fourteen lncRNAs (15 probe sets) were validated in all three datasets
using the criteria FDR < 0.01: LOC441178, C5orf66-AS1, HCG22, FLG-AS1,
CCL14/CCL15-CCL14, LOC100506990, TRIP10, PCBP1-AS1, LINC01315, LINC00478, COX10
AS1/LOC100506974, MLLT4-AS1, MIR31HG, and DUXAP10/LINC01296. Three lncRNAs in the
validated list which showed the highest fold change (LOC441178, HCG22 and C5orf66
AS1) were verified by quantitative RT-PCR in a subset of 20 OSCCs and 10 control
samples. In silico prediction of their functional role has given us directions
for further investigation.
PMID- 28415560
TI - Gallbladder papillary neoplasms share pathological features with intraductal
papillary neoplasm of the bile duct.
AB - Intraductal papillary neoplasm of the bile duct (IPNB) has been widely
recognized. However, the knowledge of intracystic papillary neoplasm of the
gallbladder (IPNG) including papillary adenoma and adenocarcinoma is not well
defined. In this study, we compared the clinicopathological and
immunohistochemical features between 32 IPNG cases and 32 IPNB cases. IPNG-1 (low
high grade dysplasia) exhibited an earlier onset age, smaller tumor size and
lower level of CK20 expression compared to IPNG-2 (invasive carcinoma).
Histologically, pancreaticobiliary and intestinal subtype accounted for nearly
half of IPNG or IPNB (44.4% and 48.1% vs. 44.0% and 44.0%), respectively.
Immunohistochemically, 88.9% of IPNG and 92.0% of IPNB cases were positive for
MUC1, and 96.3% and 92.0% for CK7, respectively. CDX2 and MUC2 were more highly
expressed in the intestinal subtype than in other subtypes. CK20 expression
increased in parallel with tumor progression. In addition, 53.1% of IPNG cases
and 68.6% of IPNB cases exhibited invasive carcinoma, and showed significant
survival advantages to conventional gallbladder adenocarcinoma and
cholangiocarcinoma, respectively. In conclusion, papillary adenoma and
adenocarcinoma of the gallbladder can be recognized as different pathological
stages of IPNG, and they share pathological features with IPNB.
PMID- 28415561
TI - Phosphorylation of HSF1 at serine 326 residue is related to the maintenance of
gynecologic cancer stem cells through expression of HSP27.
AB - Cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) are defined by
their higher tumor-initiating ability, self-renewal capacity and differentiation
capacity. CSCs/CICs are resistant to several therapies including chemotherapy and
radiotherapy. CSCs/CICs thus are thought to be responsible for recurrence and
distant metastasis, and elucidation of the molecular mechanisms of CSCs/CICs are
essential to design CSC/CIC-targeting therapy. In this study, we analyzed the
molecular aspects of gynecological CSCs/CICs. Gynecological CSCs/CICs were
isolated as ALDH1high cell by Aldefluor assay. The gene expression profile of
CSCs/CICs revealed that several genes related to stress responses are
preferentially expressed in gynecological CSCs/CICs. Among the stress response
genes, a small heat shock protein HSP27 has a role in the maintenance of
gynecological CSCs/CICs. The upstream transcription factor of HSP27, heat shock
factior-1 (HSF1) was activated by phosphorylation at serine 326 residue (pSer326)
in CSCs/CICs, and phosphorylation at serine 326 residue is essential for
induction of HSP27. Immunohistochemical staining using clinical ovarian cancer
samples revealed that higher expressions of HSF1 pSer326 was related to poorer
prognosis. These findings indicate that activation of HSF1 at Ser326 residue and
transcription of HSP27 is related to the maintenance of gynecological CSCs/CICs.
PMID- 28415562
TI - Genome-wide association study of high-altitude pulmonary edema in a Han Chinese
population.
AB - A two-stage genome-wide association study (GWAS) was performed to identify and
analyze genes and single nucleotide polymorphisms (SNPs) associated with high
altitude pulmonary edema (HAPE) in a Han Chinese patient population. In the first
stage, DNA samples from 68 patients with recurrent HAPE were scanned using
Affymetrix SNP Array 6.0 Chips, and allele frequencies were compared to those of
84 HapMap CHB samples to identify candidate SNPs. In the second stage, the 77
identified candidate SNPs were examined in an independent cohort of samples from
199 HAPE patients and 304 controls. Associations between SNPs and HAPE risk were
tested using various genetic models. Of the 77 original SNPs, 7 were found to be
associated with HAPE susceptibility in the second stage of the study. GO and
pathway enrichment analysis of the 7 SNPs revealed 5 adjacent genes involved in
various processes, including regulation of nucleoside diphosphate metabolism,
thyroid hormone catabolism, and low-density lipoprotein receptor activity. These
results suggest the identified SNPs and genes may contribute to the
physiopathology of HAPE.
PMID- 28415563
TI - GD2 expression in breast cancer.
AB - Breast cancer (BC) is a heterogeneous disease, including different subtypes
having diverse incidence, drug-sensitivity and survival rates. In particular,
claudin-low and basal-like BC have mesenchymal features with a dismal prognosis.
Disialoganglioside GD2 is a typical neuroectodermal antigen expressed in a
variety of cancers. Despite its potential relevance in cancer diagnostics and
therapeutics, the presence and role of GD2 require further investigation,
especially in BC. Therefore, we evaluated GD2 expression in a cohort of BC
patients and its correlation with clinical-pathological features.Sixty-three
patients with BC who underwent surgery without prior chemo- and/or radiotherapy
between 2001 and 2014 were considered. Cancer specimens were analyzed by
immunohistochemistry and GD2-staining was expressed according to the percentage
of positive cells and by a semi-quantitative scoring system.Patient
characteristics were heterogeneous by age at diagnosis, histotype, grading, tumor
size, Ki-67 and receptor-status. GD2 staining revealed positive cancer cells in
59% of patients. Among them, 26 cases (41%) were labeled with score 1+ and 11
(18%) with score 2+. Notably, the majority of metaplastic carcinoma specimens
stained positive for GD2. The univariate regression logistic analysis revealed a
significant association of GD2 with triple-receptor negative phenotype and older
age (> 78) at diagnosis.We demonstrate for the first time that GD2 is highly
prevalent in a cohort of BC patients clustering on very aggressive BC subtypes,
such as triple-negative and metaplastic variants.
PMID- 28415565
TI - Rad52 deficiency decreases development of lung squamous cell carcinomas by
enhancing immuno-surveillance.
AB - RAD52 is involved in homologous recombination and DNA repair. This study focuses
on lung cancer progression and how the DNA repair gene, Rad52, enables tumor
cells to have sufficient genome integrity, i.e., the ability to repair lethal DNA
damage, to avoid cell death. In this report, we analyze the phenotypic
differences between wild type and Rad52-/- in inhibition of tumor phenotypes
including cell growth, viability, cytolysis, and immune profiling. We
demonstrated that loss of Rad52 not only increases the death of cells undergoing
carcinogen-induced transformation in vivo, but that Rad52 loss also augments in
vivo antitumor activity through an enhanced capacity for direct killing of LLC
tumor cells by stimulated Rad52-/- NK and CD8+ T cells. We hypothesize that upon
DNA damage, wild type cells attempt to repair DNA lesions, but those cells that
survive will continue to divide with damage and a high likelihood of progressing
to malignancy. Loss of Rad52, however, appears to increase genomic instability
beyond a manageable threshold, acceding the damaged cells to death before they
are able to become tumor cells. Our results suggest a key role for the complex
interplay between the DNA damage response and host immunity in determining risk
for Squamous Cell Lung Carcinoma.
PMID- 28415566
TI - Co-targeting of DNA, RNA, and protein molecules provides optimal outcomes for
treating osteosarcoma and pulmonary metastasis in spontaneous and experimental
metastasis mouse models.
AB - Metastasis is a major cause of mortality for cancer patients and remains as the
greatest challenge in cancer therapy. Driven by multiple factors, metastasis may
not be controlled by the inhibition of single target. This study was aimed at
assessing the hypothesis that drugs could be rationally combined to co-target
critical DNA, RNA and protein molecules to achieve "saturation attack" against
metastasis. Independent actions of the model drugs DNA-intercalating doxorubicin,
RNA-interfering miR-34a and protein-inhibiting sorafenib on DNA replication, RNA
translation and protein kinase signaling in highly metastatic, human osteosarcoma
143B cells were demonstrated by the increase of gammaH2A.X foci formation,
reduction of c-MET expression and inhibition of Erk1/2 phosphorylation,
respectively, and optimal effects were found for triple-drug combination.
Consequently, triple-drug treatment showed a strong synergism in suppressing 143B
cell proliferation and the greatest effects in reducing cell invasion. Compared
to single- and dual-drug treatment, triple-drug therapy suppressed pulmonary
metastases and orthotopic osteosarcoma progression to significantly greater
degrees in orthotopic osteosarcoma xenograft/spontaneous metastases mouse models,
while none showed significant toxicity. In addition, triple-drug therapy improved
the overall survival to the greatest extent in experimental metastases mouse
models. These findings demonstrate co-targeting of DNA, RNA and protein molecules
as a novel therapeutic strategy for the treatment of metastasis.
PMID- 28415569
TI - Interleukin-2-regulatory T cell axis critically regulates maintenance of
hematopoietic stem cells.
AB - The role of IL-2 in HSC maintenance is unknown. Here we show that Il2-/- mice
develop severe anomalies in HSC maintenance leading to defective hematopoiesis.
Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis,
myelopoiesis was enhanced in Il2-/- mice. Investigation of the underlying
mechanisms of dysregulated hematopoiesis in Il2-/- mice shows that the IL-2-Treg
cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of
Treg activity resulted in increased IFN-gamma production by activated T cells and
an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg
population successfully rescued HSC maintenance in Il2-/- mice, preventing IFN
gamma activity could do the same even in the absence of Treg cells. Our study
suggests that equilibrium in IL-2 and IFN-gamma activity is critical for steady
state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN
gamma treatment might help to restore hematopoiesis.
PMID- 28415568
TI - Non-coding RNAs as emerging regulators of epithelial to mesenchymal transition in
non-small cell lung cancer.
AB - Non-small cell lung cancer (NSCLC) remains a major health problem that patients
suffer from around the world. The epithelial to mesenchymal transition (EMT) has
attractive roles in increasing malignant potential and reducing sensitivity to
conventional therapeutics in NSCLC cells. Meanwhile, it is now evident that non
coding RNAs (ncRNAs), primarily microRNAs and long non-coding RNAs contribute to
tumorigenesis partially via regulating EMT. This article briefly summarizes
current researches about EMT-related ncRNAs in NSCLC and discusses their crucial
roles in the complex regulatory network. Also, the authors will show the evidence
that ncRNAs not only contribute to cancer cells migration and invasion, but also
take charge of the resistance of chemotherapy, radiotherapy and EGFR-TIKs. Then,
we will further discuss the potential of inhibition of EMT via manipulating
relevant ncRNAs to change our current treatment of NSCLC patients.
PMID- 28415564
TI - Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges
for SphK as an oncotarget.
AB - The various sphingosine kinase (SphK) isoenzymes (isozymes) and isoforms, key
players in normal cellular physiology, are strongly implicated in cancer and
other diseases. Mutations in SphKs, that may justify abnormal physiological
function, have not been recorded. Nonetheless, there is a large and growing body
of evidence demonstrating the contribution of gain or loss of function and the
imbalance in the SphK/S1P rheostat to a plethora of pathological conditions
including cancer, diabetes and inflammatory diseases. SphK is expressed as two
isozymes SphK1 and SphK2, transcribed from genes located on different chromosomes
and both isozymes catalyze the phosphorylation of sphingosine to S1P. Expression
of each SphK isozyme produces alternately spliced isoforms. In recent years the
importance of the contribution of SpK1 expression to treatment resistance in
cancer has been highlighted and, additionally, differences in treatment outcome
appear to also be dependent upon SphK isoform expression. This review focuses on
an exciting emerging area of research involving SphKs functions, expression and
subcellular localization, highlighting the complexity of targeting SphK in cancer
and also comorbid diseases. This review also covers the SphK isoenzymes and
isoforms from a historical perspective, from their first discovery in murine
species and then in humans, their role(s) in normal cellular function and in
disease processes, to advancement of SphK as an oncotarget.
PMID- 28415570
TI - Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus
erythematosus risk.
AB - The association of polymorphisms in programmed cell death 1 (PDCD1) gene with
systemic lupus erythematosus (SLE) risk is inconsistent across different studies.
This meta-analysis is aimed to provide reliable evidence to the association of
five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE
risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were
included in this meta-analysis. PD1.3 polymorphism was significantly associated
with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA
vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13
1.7). In the stratified analyses based on ethnicity, we found a significant
association in Caucasians and in Mexicans. In the subgroup analyses by gender, a
significant association was found between PD1.3 polymorphism and SLE risk in
males. The results also suggested an association between the PD1.6 polymorphism
and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta
analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE,
particularly in Caucasians, while PD1.6 may be a protective factor to SLE.
PMID- 28415571
TI - Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and
triple-negative essential thrombocythemia.
AB - Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative
neoplasm. We have reported that increased activated B cells can facilitate
platelet production mediated by cytokines regardless JAK2 mutational status in
ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL
unmutated ET and primary myelofibrosis. Here we sought to screen for CALR
mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese
ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell
activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression
and intracellular levels of interleukin (IL)-1beta/IL-6 and the expression of
CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration
was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of
54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%)
patients with concomitant JAK2V617F mutations. Compared to JAK2V617F mutation,
CALR mutations correlated with younger age at diagnosis (p=0.04), higher platelet
count (p=0.004), lower hemoglobin level (p=0.013) and lower leukocyte count
(p=0.013). Multivariate analysis adjusted for age, sex, follow-up period and
hematological parameters confirmed that increased activated B cells were
universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients
when compared to healthy adults. JAK2- and CALR-mutated ET have significantly
higher fraction of B cells with TLR4 expression when compared to triple-negative
ET (p=0.019 and 0.02, respectively). CALR-mutated ET had significantly higher
number of CD69-positive activated B cells when compared to triple-negative ET
(p=0.035). In conclusion, increased B cell activation is present in ET patients
across different mutational subgroups.
PMID- 28415572
TI - Inhibition of iron overload-induced apoptosis and necrosis of bone marrow
mesenchymal stem cells by melatonin.
AB - Iron overload induces severe damage to several vital organs such as the liver,
heart and bone, and thus contributes to the dysfunction of these organs. The aim
of this study is to investigate whether iron overload causes the apoptosis and
necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent
its toxicity. Perls' Prussion blue staining showed that exposure to increased
concentrations of ferric ammonium citrate (FAC) induced a gradual increase of
intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC
decreased the viability of BMSCs in a concentration-dependent manner. Notably,
melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it
was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore,
melatonin pretreatment suppressed FAC-induced reactive oxygen species
accumulation. Western blot showed that exposure to FAC resulted in the decrease
of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and
Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were
significantly inhibited by melatonin treatment. At last, melatonin receptor
blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis
by melatonin. Taken together, melatonin protected BMSCs from iron overload
induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1
and RIP3 pathways.
PMID- 28415573
TI - Elevated TATA-binding protein expression drives vascular endothelial growth
factor expression in colon cancer.
AB - The TATA-binding protein (TBP) plays a central role in eukaryotic gene
transcription. Given its key function in transcription initiation, TBP was
initially thought to be an invariant protein. However, studies showed that TBP
expression is upregulated by oncogenic signaling pathways. Furthermore, depending
on the cell type, small increases in cellular TBP amounts can induce changes in
cellular growth properties towards a transformed phenotype. Here we sought to
identify the specific TBP-regulated gene targets that drive its ability to induce
tumorigenesis. Using microarray analysis, our results reveal that increases in
cellular TBP concentrations produce selective alterations in gene expression that
include an enrichment for genes involved in angiogenesis. Accordingly, we find
that TBP levels modulate VEGFA expression, the master regulator of angiogenesis.
Increases in cellular TBP amounts induce VEGFA expression and secretion to
enhance cell migration and tumor vascularization. TBP mediates changes in VEGFA
transcription requiring its recruitment at a hypoxia-insensitive proximal TSS,
revealing a mechanism for VEGF regulation under non-stress conditions. The
results are clinically relevant as TBP expression is significantly increased in
both colon adenocarcinomas as well as adenomas relative to normal tissue.
Furthermore, TBP expression is positively correlated with VEGFA expression.
Collectively, these studies support the idea that increases in TBP expression
contribute to enhanced VEGFA transcription early in colorectal cancer development
to drive tumorigenesis.
PMID- 28415574
TI - Prognostic roles of Notch receptor mRNA expression in human ovarian cancer.
AB - Aberrant activation of Notch signaling pathway has been correlated with high
grade ovarian carcinoma and carcinogenesis. However, the predictive and
prognostic values of Notch signaling pathway in ovarian cancer patients remains
unclear. We utilize "The Kaplan-Meier plotter" (KM plotter) background database
to access the prognostic values including overall survival (OS), progression-free
survival (PFS), as well as post-progression survival (PPS) of four Notch receptor
mRNA expression in ovarian cancer patients. Notch1 mRNA high expression was not
correlated with OS, PFS and PPS for all ovarian cancer patients, but
significantly correlated with poor PFS in TP53 wild type and favorite PFS in TP53
mutation type ovarian cancer patients. Notch2 mRNA high expression was
significantly correlated with poor PFS for all ovarian cancer patients,
especially in grade II patients. Notch3 mRNA high expression was significantly
correlated with favorite PFS for all ovarian cancer patients. Notch4 mRNA high
expression was significantly correlated with favorite OS, but not PFS and PPS for
all ovarian cancer patients. The results strongly support that there are distinct
prognostic values of four Notch receptor mRNA expression in ovarian cancer
patients.
PMID- 28415575
TI - IK channel activation increases tumor growth and induces differential behavioral
responses in two breast epithelial cell lines.
AB - Many potassium channel families are over-expressed in cancer, but their
mechanistic role in disease progression is poorly understood. Potassium channels
modulate membrane potential (Vmem) and thereby influence calcium ion dynamics and
other voltage-sensitive signaling mechanisms, potentially acting as
transcriptional regulators. This study investigated the differential response to
over-expression and activation of a cancer-associated potassium channel, the
intermediate conductance calcium-activated potassium channel (IK), on aggressive
behaviors in mammary epithelial and breast cancer cell lines. IK was over
expressed in the highly metastatic breast cancer cell line MDA-MB-231 and the
spontaneously immortalized breast epithelial cell line MCF-10A, and the effect on
cancer-associated behaviors was assessed. IK over-expression increased primary
tumor growth and metastasis of MDA-MB-231 in orthotopic xenografts, demonstrating
for the first time in any cancer type that increased IK is sufficient to promote
cancer aggression. The primary tumors had similar vascularization as determined
by CD31 staining and similar histological characteristics. Interestingly, despite
the increased in vivo growth and metastasis, neither IK over-expression nor
activation with agonist had a significant effect on MDA-MB-231 proliferation,
invasion, or migration in vitro. In contrast, IK decreased MCF-10A proliferation
and invasion through Matrigel but had no effect on migration in a scratch-wound
assay. We conclude that IK activity is sufficient to promote cell aggression in
vivo. Our data provide novel evidence supporting IK and downstream signaling
networks as potential targets for cancer therapies.
PMID- 28415576
TI - Clinicopathological features of small cell carcinoma of the uterine cervix in the
surveillance, epidemiology, and end results database.
AB - To investigate the clinicopathological characteristics and survival of small cell
carcinoma of the cervix using Surveillance, Epidemiology, and End Results
database. Patients with a diagnosis of small cell carcinoma of the cervix were
included between 1988 and 2012. Kaplan-Meier method and Cox regression models
were used. A total of 487 patients were included. Of the patients with known
International Federation of Gynecology and Obstetrics stage and tumor grade, the
stage IV disease was diagnosed in 37.9% patients, and 98.5% patients had poorly
or undifferentiated histology. The 5-year cause specific survival and overall
survival were 33.0% and 29.4%, respectively. In multivariate analysis, increasing
age, advanced stage, and treatment by primary radiotherapy were associated with
worse survival outcomes. Small cell carcinoma of the cervix is a rare disease
with aggressive characteristics and prone to metastasize and is dismal in
prognosis. Reduced survival was associated with increasing age, advanced stage,
and treatment by primary radiotherapy.
PMID- 28415577
TI - High expression of B7-H6 in human glioma tissues promotes tumor progression.
AB - B7-H6, a new member of B7-family ligand, also known as NCR3LG1, plays an
important role in NK cells mediated immune responses. Many studies have shown
that it is highly expressed in various human cancers, and its expression levels
are significantly associated with cancer patients' clinicopathological parameters
and postoperative prognoses. But, still the exact role of B7-H6 expression in
human glioma remains elusive. In the present study, we have characterized the B7
H6 expression in the human glioma tissues as well as glioma cell lines, U87 and
U251. We observed that B7-H6 was highly expressed in the human glioma tissues,
and its expression was significantly associated with cancer progression. By using
the RNA interference technology, we successfully ablated B7-H6 expression in
human glioma cell lines to further study its contribution towards various
biological features of this malignancy. Our study identified that the B7-H6
knockdown in U87 and U251 glioma cells significantly suppressed cell
proliferation, migration, invasion, and enhanced apoptosis along with induction
of cell cycle arrest. It thus suggested that B7-H6 play an important role in the
regulation of the biological behavior of these glioma cells. However, the
detailed mechanism of B7-H6 mediated regulation of glioma cancer cell
transformation and its prognostic value merits further investigation.
PMID- 28415578
TI - High expression of miR-125b-2 and SNORD116 noncoding RNA clusters characterize
ERG-related B cell precursor acute lymphoblastic leukemia.
AB - ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL)
subtype characterized by aberrant expression of DUX4 and ERG transcription
factors, and highly recurrent ERG intragenic deletions. ERG-related patients have
remarkably favorable outcome despite a high incidence of inauspicious IKZF1
aberrations.We describe clinical and genomic features of the ERG-related cases in
an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP
ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific
of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21
and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan
SNORD116 cluster.
PMID- 28415579
TI - Metabolite marker discovery for the detection of bladder cancer by comparative
metabolomics.
AB - Bladder cancer is one of the most common urinary tract carcinomas in the world.
Urine metabolomics is a promising approach for bladder cancer detection and
marker discovery since urine is in direct contact with bladder epithelia cells;
metabolites released from bladder cancer cells may be enriched in urine samples.
In this study, we applied ultra-performance liquid chromatography time-of-flight
mass spectrometry to profile metabolite profiles of 87 samples from bladder
cancer patients and 65 samples from hernia patients. An OPLS-DA classification
revealed that bladder cancer samples can be discriminated from hernia samples
based on the profiles. A marker discovery pipeline selected six putative markers
from the metabolomic profiles. An LLE clustering demonstrated the discriminative
power of the chosen marker candidates. Two of the six markers were identified as
imidazoleacetic acid whose relation to bladder cancer has certain degree of
supporting evidence. A machine learning model, decision trees, was built based on
the metabolomic profiles and the six marker candidates. The decision tree
obtained an accuracy of 76.60%, a sensitivity of 71.88%, and a specificity of
86.67% from an independent test.
PMID- 28415580
TI - The N-terminal polypeptide derived from viral macrophage inflammatory protein II
reverses breast cancer epithelial-to-mesenchymal transition via a PDGFRalpha
dependent mechanism.
AB - NT21MP, a 21-residue peptide derived from the viral macrophage inflammatory
protein II, competed effectively with the natural ligand of CXC chemokine
receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and
inhibit growth in breast cancer. Its role in tumor epithelial-to-mesenchymal
transition (EMT) regulation remains unknown. In this study, we evaluated the
reversal of EMT upon NT21MP treatment and examined its role in the inhibition of
EMT in breast cancer. The parental cells of breast cancer (SKBR-3 and MCF-7) and
paclitaxel-resistant (SKBR-3 PR and MCF-7 PR) cells were studied in vitro and in
combined immunodeficient mice. The mice injected with SKBR-3 PR cells were
treated with NT21MP through the tail vein or intraperitoneally with paclitaxel or
saline. Sections from tumors were evaluated for tumor weight and EMT markers
based on Western blot. In vitro, the effects of NT21MP, CXCR4 and PDGFRalpha on
tumor EMT were assessed by relative quantitative real-time reverse transcription
polymerase chain reaction, western blot and biological activity in breast cancer
cell lines expressing high or low levels of CXCR4. Our results illustrated that
NT21MP could reverse the phenotype of EMT in paclitaxel-resistant cells.
Furthermore, we found that NT21MP governed PR-mediated EMT partly due to
controlling platelet-derived growth factors A and B (PDGFA and PDGFB) and their
receptor (PDGFRalpha). More importantly, NT21MP down-regulated AKT and ERK1/2
activity, which were activated by PDGFRalpha, and eventually reversed the EMT.
Together, these results indicated that CXCR4 overexpression drives acquired
paclitaxel resistance, partly by activating the PDGFA and PDGFB/PDGFRalpha
autocrine signaling loops that activate AKT and ERK1/2. Inhibition of the
oncogenic EMT process by targeting CXCR4/PDGFRalpha-mediated pathways using
NT21MP may provide a novel therapeutic approach towards breast cancer.
PMID- 28415581
TI - Tumor physiological changes during hypofractionated stereotactic body radiation
therapy assessed using multi-parametric magnetic resonance imaging.
AB - Radiation therapy is a primary treatment for non-resectable lung cancer and
hypoxia is thought to influence tumor response. Hypoxia is expected to be
particularly relevant to the evolving new radiation treatment scheme of
hypofractionated stereotactic body radiation therapy (SBRT). As such, we sought
to develop non-invasive tools to assess tumor pathophysiology and response to
irradiation. We applied blood oxygen level dependent (BOLD) and tissue oxygen
level dependent (TOLD) MRI, together with dynamic contrast enhanced (DCE) MRI to
explore the longitudinal effects of SBRT on tumor oxygenation and vascular
perfusion using A549 human lung cancer xenografts in a subcutaneous rat model.
Intra-tumor heterogeneity was seen on multi-parametric maps, especially in BOLD,
T2* and DCE. At baseline, most tumors showed a positive BOLD signal response
(%DeltaSI) and increased T2* in response to oxygen breathing challenge,
indicating increased vascular oxygenation. Control tumors showed similar response
24 hours and 1 week later. Twenty-four hours after a single dose of 12 Gy, the
irradiated tumors showed a significantly decreased T2* (-2.9+/-4.2 ms) and
further decrease was observed (-4.0+/-6.0 ms) after 1 week, suggesting impaired
vascular oxygenation. DCE revealed tumor heterogeneity, but showed minimal
changes following irradiation. Rats were cured of the primary tumors by 3x12 Gy,
providing long term survival, though with ultimate metastatic recurrence.
PMID- 28415582
TI - Respiratory status determines the effect of emodin on cell viability.
AB - The anthraquinone emodin has been shown to have antineoplastic properties and a
wealth of unconnected effects have been linked to its use, most of which are
likely secondary outcomes of the drug treatment. The primary activity of emodin
on cells has remained unknown. In the present study we demonstrate dramatic and
extensive effects of emodin on the redox state of cells and on mitochondrial
homeostasis, irrespectively of the cell type and organism, ranging from the yeast
Saccharomyces cerevisiae to human cell lines and primary cells. Emodin binds to
redox-active enzymes and its effectiveness depends on the oxidative and
respiratory status of cells. We show that cells with efficient respiratory
metabolism are less susceptible to emodin, whereas cells under glycolytic
metabolism are more vulnerable to the compound. Our findings indicate that emodin
acts in a similar way as known uncouplers of the mitochondrial electron transport
chain and causes oxidative stress that particularly disturbs cancer cells.
PMID- 28415583
TI - Prognostic value of circulating endothelial cells in metastatic colorectal
cancer.
AB - BACKGROUND: There is urgent need for improved staging in patients with metastatic
colorectal cancer (mCRC). In this study, we evaluated the prognostic value of
circulating endothelial cells (CEC) in comparison with circulating tumor cells
(CTC) in patients with mCRC amenable for potentially curative surgery. METHODS: A
total of 140 patients were enrolled prospectively. CTC and CEC were measured with
the CellSearch System (Veridex, NJ, USA). Cut-off values were determined using
ROC analyses. Prognostic factors were identified by Cox proportional hazards
models. RESULTS: ROC analyses revealed >= 21 CEC as cut-off levels for detection,
which was present in 68 (49%). CEC detection was associated with female gender (p
= 0.03) only, whereas CTC detection was associated with presence of the primary
tumor (p = 0.007), metastasis size (p < 0.001), bilobar liver metastases (p =
0.02), CEA (p < 0.001) and CA 19-9 levels (p < 0.001). On multivariate analysis
only CEC detection (HR 1.81; p = 0.03) and preoperative CA19-9 levels (HR 2.28, p
= 0.005) were revealed as independent predictors of poor survival. CONCLUSIONS:
CEC are of stronger prognostic value than CTC. Further studies are required to
validate these results and to evaluate CEC as predictive biomarker for systemic
therapy alone as well as in combination with other markers such as CA19-9.
PMID- 28415584
TI - Folic acid phenotype (FAP) is a superior biomarker predicting response to
pemetrexed-based chemotherapy in malignant pleural mesothelioma.
AB - BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare tumor linked to a
dismal prognosis. Even the most effective chemotherapeutical regime of pemetrexed
combined with cisplatin leads to a remission-rate of only about 40%. The reasons
for the rather poor efficacy remain largely unknown. RESULTS: Phenotypes were
significantly associated with progression (p=0.0279) and remission (p=0.0262).
Cox-regression revealed significant associations between SLC19A1/TYMS-ratio
(p=0.0076) as well as FPGS/TYMS-ratio (p=0.0026) and OS. For differentiation by
risk-groups, COXPH identified a strong correlation (p=0.0008). METHODS: 56 MPM
specimens from patients treated with pemetrexed were used for qPCR analysis.
Phenotypes and risk groups were defined by their expression levels of members of
the folic acid metabolism and correlated to survival and objective response.
CONCLUSION: Our results indicate that the balance between folic acid uptake,
activation and metabolism plays a crucial role in response to pemetrexed-based
chemotherapy and the prognosis of MPM patients. Implementing this marker profile
in MPM stratification may help to individualize MPM-therapy more efficiently.
PMID- 28415586
TI - Promoting oligodendroglial-oriented differentiation of glioma stem cell: a
repurposing of quetiapine for the treatment of malignant glioma.
AB - As a major contributor of chemotherapy resistance and malignant recurrence,
glioma stem cells (GSCs) have been proposed as a target for the treatment of
gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical
antipsychotic, for the treatment of malignant glioma, we established mouse models
with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft
tumors, using GSCs purified from glioblastoma cell line GL261. We investigated
antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on
GSCs. Our data demonstrated that (i) QUE monotherapy can effectively suppress
GSCs-initiated tumor growth; (ii) QUE has synergistic effects with temozolomide
(TMZ) on glioma suppression, and importantly, QUE can effectively suppress TMZ
resistant (or -escaped) tumors generated from GSCs; (iii) mechanistically, the
anti-glioma effect of QUE was due to its actions of promoting the differentiation
of GSCs into oligodendrocyte (OL)-like cells and its inhibitory effect on the
Wnt/beta-catenin signaling pathway. Together, our findings suggest an effective
approach for anti-gliomagenic treatment via targeting OL-oriented differentiation
of GSCs. This also opens a door for repurposing QUE, an FDA approved drug, for
the treatment of malignant glioma.
PMID- 28415587
TI - Detection of a combination of serum IgG and IgA antibodies against selected
mycobacterial targets provides promising diagnostic signatures for active TB.
AB - Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB)
disease often show a lack of specificity in TB endemic regions, which is mainly
due to a high background prevalence of LTBI. Here, we investigated the combined
performance of the responses of different Ig classes to selected mycobacterial
antigens in primary healthcare clinic attendees with signs and symptoms
suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM
and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and
19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals
who underwent diagnostic work-up for TB after presenting with symptoms and signs
compatible with possible active TB were evaluated. Active TB was excluded in 42
individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of
whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The
leading single serodiagnostic markers to differentiate between the presence or
absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and
specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4
antibodies further improved this performance to accuracies above 95%. After
successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA
and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased.
These results show the potential of extending investigation of anti-tuberculous
IgG responses to include IgM and IgA responses against selected protein and non
protein antigens in differentiating active TB from other respiratory diseases in
TB endemic settings.
PMID- 28415588
TI - Smad inhibitor induces CSC differentiation for effective chemosensitization in
cyclin D1- and TGF-beta/Smad-regulated liver cancer stem cell-like cells.
AB - Understanding cancer stem cell (CSC) maintenance pathways is critical for the
development of CSC-targeting therapy. Here, we investigated the functional role
of the cyclin D1-dependent activation of Smad2/3 and Smad4 in hepatocellular
carcinoma (HCC) CSCs and in HCC primary tumors. Cyclin D1 sphere-derived
xenograft tumor models were employed to evaluate the therapeutic effects of a
Smad inhibitor in combination with chemotherapy. Cyclin D1 overexpression confers
stemness properties by enhancing single sphere formation, enhancing the CD90+ and
EpCAM+ population, increasing stemness gene expression, and increasing
chemoresistance. Cyclin D1 interacts with and activates Smad2/3 and Smad4 to
result in cyclin D1-Smad2/3-Smad4 signaling-regulated liver CSC self-renewal. The
cyclin D1-dependent activation of Smad2/3 and Smad4 is also found in HCC patients
and predicts disease progression. A Smad inhibitor impaired cyclin D1-Smad
mediated self-renewal, resulting in the chemosensitization. Thus, pretreatment
with a Smad inhibitor followed by chemotherapy not only successfully suppressed
tumor growth but also eliminated 57% of the tumors in a cyclin D1 sphere-derived
xenograft model. Together, The cyclin D1-mediated activation of Smad2/3 and Smad4
is an important regulatory mechanism in liver CSC self-renewal and stemness.
Accordingly, a Smad inhibitor induced CSC differentiation and consequently
significant chemosensitization, which could be an effective strategy to target
CSCs.
PMID- 28415589
TI - GABAergic neurons in nucleus accumbens are correlated to resilience and
vulnerability to chronic stress for major depression.
AB - BACKGROUND: Major depression, persistent low mood, is one of common psychiatric
diseases. Chronic stressful life is believed to be a major risk factor that leads
to dysfunctions of the limbic system. However, a large number of the individuals
with experiencing chronic stress do not suffer from major depression, called as
resilience. Endogenous mechanisms underlying neuronal invulnerability to chronic
stress versus major depression are largely unknown. As GABAergic neurons are
vulnerable to chronic stress and their impairments is associated with major
depression, we have examined whether the invulnerability of GABAergic neurons in
the limbic system is involved in resilience. RESULTS: GABAergic neurons in the
nucleus accumbens from depression-like mice induced by chronic unpredictable mild
stress appear the decreases in their GABA release, spiking capability and
excitatory input reception, compared with those in resilience mice. The levels of
decarboxylase and vesicular GABA transporters decrease in depression-like mice,
but not resilience. MATERIALS AND METHODS: Mice were treated by chronic
unpredictable mild stress for three weeks. Depression-like behaviors or
resilience was confirmed by seeing whether their behaviors change significantly
in sucrose preference, Y-maze and forced swimming tests. Mice from controls as
well as depression and resilience in response to chronic unpredictable mild
stress were studied in terms of GABAergic neuron activity in the nucleus
accumbens by cell electrophysiology and protein chemistry. CONCLUSIONS: The
impairment of GABAergic neurons in the nucleus accumbens is associated with major
depression. The invulnerability of GABAergic neurons to chronic stress may be one
of cellular mechanisms for the resilience to chronic stress.
PMID- 28415590
TI - Multiple anti-tumor effects of Reparixin on thyroid cancer.
AB - BACKGROUND: Expression of IL-8 and its receptors CXCR1 and CXCR2 is a common
occurrence in human epithelial thyroid cancer (TC). In human TC samples, IL-8
expression is associated with tumor progression. IL-8 enhances proliferation,
survival, motility, and leads to the maintenance of stemness features and tumor
initiating ability of TC cells. Here, we studied the effects of Reparixin
(formerly Repertaxin), a small molecular weight CXCR1 and CXCR2 inhibitor, on the
malignant phenotype of various TC cell lines. RESULTS: Reparixin impaired the
viability of epithelial thyroid cancerous cells, but not that of the non
malignant counterpart. Reparixin treatment significantly decreased TC cell
survival, proliferation, Epithelial-to-Mesenchymal Transition (EMT) and stemness.
CXCR1 and CXCR2 silencing abolished these effects. Reparixin sensitized TC cells
to Docetaxel and Doxorubicin in culture. Used as single agent, Reparixin
significantly inhibited TC cell tumorigenicity in immunodeficient mice. Finally,
Reparixin potentiated the effects of Docetaxel on TC cell xenotransplants in
mice. MATERIALS AND METHODS: We assessed the effects of Reparixin on TC cell
viability (by growth curves, BrdU incorporation, TUNEL assay), EMT (by RT-PCR,
Flow Cytometry, Migration assays), stemness (by RT-PCR, Flow Cytometry, sphere
formation and self-renewal), and tumorigenicity (by xenotransplantation in nude
mice). CONCLUSIONS: The present study suggests that Reparixin, both alone and in
combination with classic chemotherapics, represents a novel potential therapeutic
strategy for aggressive forms of TC.
PMID- 28415591
TI - The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and
fibroblasts in fibrotic lung disease.
AB - Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available
treatment options. Recently, the involvement of purinergic receptor subtypes in
the pathogenesis of different lung diseases has been demonstrated. Here we
investigated the role of the purinergic receptor subtype P2Y2 in the context of
fibrotic lung diseases.The concentration of different nucleotides was measured in
the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals
with bleomycin-induced pulmonary fibrosis. In addition expression of P2Y2
receptors by different cell types was determined. To investigate the functional
relevance of P2Y2 receptors for the pathogenesis of the disease the bleomycin
model of pulmonary fibrosis was used. Finally, experiments were performed in
pursuit of the involved mechanisms.Compared to healthy individuals or vehicle
treated animals, extracellular nucleotide levels in the BAL fluid were increased
in patients with IPF and in mice after bleomycin administration, paralleled by a
functional up-regulation of P2Y2R expression. Both bleomycin-induced inflammation
and fibrosis were reduced in P2Y2R-deficient compared to wild type animals.
Mechanistic studies demonstrated that recruitment of neutrophils into the lungs,
proliferation and migration of lung fibroblasts as well as IL6 production are key
P2Y2R mediated processes.Our results clearly demonstrate the involvement of P2Y2R
subtypes in the pathogenesis of fibrotic lung diseases in humans and mice and
hence support the development of selective P2Y2R antagonists for the treatment of
IPF.
PMID- 28415592
TI - Identification and functional analysis of differentially expressed genes in
poorly differentiated hepatocellular carcinoma using RNA-seq.
AB - Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis
compared to moderately differentiated (MD) and well differentiated (WD) HCC. We
aimed to identify differentially expressed genes (DEGs) to explore the mechanism
of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non
tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus
identified and functionally analyzed. Further RT-PCR was performed to validate
DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for
WD). A total of 681 PD DEGs were detected, including 368 up-regulated and 313
down-regulated genes. Less DEGs were found for MD and especially for WD HCC.
Through bioinformatics analysis, PD HCC DEGs were enriched in liver tissue and
liver cancer cells, and in biological process and pathway including metabolism,
cell cycle, translation and blood coagulation. Potential drugs and genetic
perturbations were found to reverse the cancer condition. The RT-PCR results
showed consistency with RNA-seq in the validation of 4 DEGs specific for PD HCC.
This study detected and validated DEGs of PD HCC, which provides useful
information on molecular mechanism of PD HCC for development of new biomarkers,
therapeutic targets and drugs.
PMID- 28415594
TI - Interaction of Epstein-Barr virus genes with human gastric carcinoma
transcriptome.
AB - Gastric carcinoma (GC) is a leading cause of mortality. 10% of GC cases are
related with EBV (Epstein-Barr virus) infection. The detailed mechanistic roles
EBV genes play and especially the interaction between the viral genes and human
genes in GC remain unclear. In this study, raw fastq data from 285 GC samples
were downloaded from TCGA (The Cancer Genome Atlas), including 25 EBV positive
(EBV+) GC samples and 260 EBV negative (EBV-) GC samples. RNA-seq based
expression data were generated for both human genes (among all the samples) and
for the EBV genes (among the 25 EBV+ samples). Bioinformatics analyses were
performed to identify differentially expressed (DEx) human genes and DEx KEGG
pathways in EBV+ vs. EBV- samples and co-expressed human gene modules and hub
genes among the DEx genes. Within the EBV+ samples, analyses were conducted to
find correlation between EBV gene expression and the human gene expression
modules, between EBV gene expression and the human hub genes, and between EBV
gene expression and the DEx human pathways. EBV genes LMP-1, BALF1 and BALF2 were
found to have significant correlation with human hub genes, CNTD2 and VANGL2. EBV
genes BALF4 and BALF5 were found to correlate with human pathways, including Jak
STAT signaling and Phosphatidylinositol Signaling System. Our study has revealed
the coordinated expression patterns between EBV and human GC transcriptome and
identified several key EBV genes that may play an important role in EBV+ GC
pathogenesis through their interactions with human genes and pathways.
PMID- 28415593
TI - Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with
leukemia relapse and leukemia-free survival in adults with B-cell acute
lymphoblastic leukemia and normal cytogenetics.
AB - Relapse is the major cause of treatment-failure in adults with B-cell acute
lymphoblastic leukemia (ALL) achieving complete remission after induction
chemotherapy. Greater precision identifying persons likely to relapse is
important. We did bio-informatics analyses of transcriptomic data to identify
mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate
genes for validation 7 of which proved significantly-associated with B-cell ALL.
We next focused on function and clinical correlations of the cysteine and glycine
rich protein 2 (CSRP2). Quantitative real-time polymerase chain reaction (RT
qPCR) was used to examine gene transcript levels in bone marrow samples from 236
adults with B-cell ALL compared with samples from normals. CSRP2 was over
expressed in 228 out of 236 adults (97%) with newly-diagnosed B-cell ALL. A
prognostic value was assessed in 168 subjects. In subjects with normal
cytogenetics those with high CSRP2 transcript levels had a higher 5-year
cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS)
compared with subjects with low transcript levels (56% [95% confidence interval,
53, 59%] vs. 19% [18, 20%]; P = 0.011 and 41% [17, 65%] vs. 80% [66-95%]; P =
0.007). In multivariate analyses a high CSRP2 transcript level was independently
associated with CIR (HR = 5.32 [1.64-17.28]; P = 0.005) and RFS (HR = 5.56 [1.87,
16.53]; P = 0.002). Functional analyses indicated CSRP2 promoted cell
proliferation, cell-cycle progression, in vitro colony formation and cell
migration ability. Abnormal CSRP2 expression was associated with resistance to
chemotherapy; sensitivity was restored by down-regulating CSRP2 expression.
PMID- 28415595
TI - 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast
cancer.
AB - PURPOSE: In bone-metastatic breast cancer patients, there are no current imaging
biomarkers to identify which patients have worst prognosis. The purpose of our
study was to investigate if skeletal tumor burden determined by 18F-Fluoride
PET/CT correlates with clinical outcomes and may help define prognosis throughout
the course of the disease. RESULTS: Bone metastases were present in 49 patients.
On multivariable analysis, skeletal tumor burden was significantly and
independently associated with overall survival (p < 0.0001) and progression free
survival (p < 0.0001). The simple presence of bone metastases was associated with
time to bone event (p = 0.0448). MATERIALS AND METHODS: We quantified the
skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer
patients (40 for primary staging and the remainder for restaging after therapy).
Clinical parameters, primary tumor characteristics and skeletal tumor burden were
correlated to overall survival, progression free-survival and time to bone event.
The median follow-up time was 19.5 months. CONCLUSIONS: 18F-Fluoride PET/CT
skeletal tumor burden is a strong independent prognostic imaging biomarker in
breast cancer patients.
PMID- 28415596
TI - Renal mass biopsy using Raman spectroscopy identifies malignant and benign renal
tumors: potential for pre-operative diagnosis.
AB - The accuracy of renal mass biopsy to diagnose malignancy can be affected by
multiple factors. Here, we investigated the feasibility of Raman spectroscopy to
distinguish malignant and benign renal tumors using biopsy specimens. Samples
were collected from 63 patients who received radical or partial nephrectomy, mass
suspicious of cancer and distal parenchyma were obtained from resected kidney
using an 18-gauge biopsy needle. Four Raman spectra were obtained for each
sample, and Discriminant Analysis was applied for data analysis. A total of 383
Raman spectra were eventually gathered and each type of tumor had its
characteristic spectrum. Raman could separate tumoral and normal tissues with an
accuracy of 82.53%, and distinguish malignant and benign tumors with a
sensitivity of 91.79% and specificity of 71.15%. It could classify low-grade and
high-grade tumors with an accuracy of 86.98%. Besides, clear cell renal carcinoma
was differentiated with oncocytoma and angiomyolipoma with accuracy of 100% and
89.25%, respectively. And histological subtypes of cell carcinoma were
distinguished with an accuracy of 93.48%. When compared with final pathology and
biopsy, Raman spectroscopy was able to correctly identify 7 of 11 "missed" biopsy
diagnoses. These results suggested that Raman may serve as a promising non
invasive approach in the future for pre-operative diagnosis.
PMID- 28415597
TI - Phosphorylation of androgen receptors at serine 515 is a potential prognostic
marker for triple negative breast cancer.
AB - 1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths.
Molecular classifications of breast cancer have resulted in improved treatments.
However, treatments for triple negative breast cancer (TNBC) are lacking.
Analysis of molecular targets for TNBC is a priority. One potential candidate is
androgen receptor (AR) phosphorylation. This study assessed the role of AR
phosphorylation at ser81/ser515 and their two upstream effectors, cyclin
dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in
332 ductal breast cancer patients by immunohistochemistry.pERK1/2 combined with
AR-515 associated with improved cancer-specific survival (CSS, p = 0.038),
decreased size (p = 0.001), invasive grade (p < 0.001), necrosis (p = 0.003), b
lymphocytes (p = 0.020), molecular subtype (p < 0.001) and estrogen receptor
(ER)/progesterone receptor (PR)-status (p < 0.001). The cohort was therefore
stratified into ER+ve and ER-ve patients. In ER+ve tumours, pERK1/2 combined with
AR-515 associated with improved CSS (p = 0.038), smaller size (p = 0.004),
invasive grade (p = 0.001), decreased b-lymphocytes (p = 0.013) and increased
plasma cells (p = 0.048). In contrast, in TNBC patients, phosphorylation of AR
515 associated with poorer CSS (p = 0.007). pERK1/2 combined with AR-515
associated with decreased inflammation (p = 0.003), increased tumour stroma (p =
0.003) and tumour budding (p = 0.011), with trends towards decrease CSS (p =
0.065) and macrophage levels (p = 0.093).In Conclusions, AR-515 may be an
important regulator of inflammation in breast cancer potential via ERK1/2
phosphorylation. AR-515 is a potential prognostic marker and therapeutic target
for TNBC.
PMID- 28415598
TI - Caloric restriction delays early phases of carcinogenesis via effects on the
tissue microenvironment.
AB - Caloric restriction (CR) is an effective and consistent means to delay aging and
the incidence of chronic diseases related to old age, including cancer. However,
the precise mechanisms responsible for the beneficial effect of CR on
carcinogenic process are yet to be identified.In the present studies the
hypothesis was tested that the CR might delay carcinogenesis via modulatory
effects exerted on the age-associated, neoplastic-prone tissue microenvironment.
Using a well characterized, orthotopic cell transplantation (Tx) system in the
rat, preneoplastic hepatocytes isolated from liver nodules were injected into
either old syngeneic rats fed ad libitum (AL) or animals of the same age given a
CR diet (70% of AL feeding). Analysis of donor-derived cell clusters performed at
10 weeks post-Tx revealed a significant shift towards smaller class sizes in the
group receiving CR diet. Clusters comprising more than 50 cells, including large
hepatic nodules, were thrice more frequent in AL vs. CR animals. Incidence of
spontaneous endogenous nodules was also decreased by CR. Markers of cell
senescence were equally expressed in the liver of AL and CR groups. However,
higher levels of SIRT1 and FOXO1 proteins were detected in CR-exposed livers,
while expression of HDAC1 and C/EBPbeta were decreased. These results are
interpreted to indicate that CR delays the emergence of age-associated neoplastic
disease through effects exerted, at least in part, on the tissue
microenvironment. Nutrient-sensing pathways might mediate such modulatory effect.
PMID- 28415599
TI - BRCA1 missense polymorphisms are associated with poor prognosis of pancreatic
cancer patients in a Chinese population.
AB - Pancreatic cancer is a highly lethal disease with limited prognostic marker.
BRAC1 and BRCA2 are two classic tumor suppressor genes which play an important
role in DNA repair. Somatic mutations and germline genetic variants on BRCA1/2
have been found associated with the tumorigenesis of pancreatic cancer. However,
the correlations between BRCA1/2 polymorphism and pancreatic cancer prognosis
remained unknown. In this study, we genotyped three tag missense variants on
BRCA1/2 in 603 sporadic pancreatic cancer patients in a Chinese population. We
found rs1799966 on BRCA1 was associated with poor prognosis of pancreatic cancer
patients with hazard ratio being 1.23 (95% CI: 1.09-1.40, P = 0.0010). Further
stratification analyses showed that significant correlation was particularly in
locally advanced stage patients with hazard ratio being 1.36 (95% CI: 1.13-1.64,
P = 0.0014), but not in patients in local stage (P = 0.1139) or metastatic stage
(P = 0.5185). Two missense variants (rs766173 and rs144848) on BRAC2 showed no
significant correlation with pancreatic cancer patients' overall survival. In
conclusion, we identified a germline missense variant on BRAC1 significantly
associated with poor prognosis of pancreatic cancer patients with locally
advanced stage. These results may contribute to the precision medicine of this
disease.
PMID- 28415600
TI - The value of MRI in evaluating the efficacy and complications with the treatment
of intra-arterial chemotherapy for retinoblastoma.
AB - Retinoblastoma is the most common intraocular malignant tumor of childhood. Intra
arterial chemotherapy (IAC) is a recently popularized technique used for the
treatment of retinoblastoma, to decrease mortality, increase preservation of the
eye, and prevent blindness. Along with the extensive use of IAC, it is important
to apply noninvasive examination methods to assess the activity of the tumor and
the risk factors for disease dissemination without histopathological
confirmation. There are few studies that have assessed the value of magnetic
resonance imaging (MRI) in evaluating the efficacy and complications of IAC for
retinoblastoma. We retrospectively analyzed the MRI features of 60 patients with
unilateral retinoblastoma given the primary treatment of IAC from January 2014 to
February 2016 in our hospital. Our study showed that MRI could well assess the
decreased activity of the tumor after IAC, presenting with diminished tumor size,
increased apparent diffusion coefficient (ADC) values (from 0.94 +/- 0.24 * 10-3
mm2/s to 2.24 +/- 0.40 * 10-3 mm2/s), and a reduced degree of enhancement of the
tumor. Our study also showed that MRI can monitor the risk factors of abnormal
enhancement of the postlaminar optic nerve, to avoid unnecessary enucleation.
Meanwhile, the results showed that the main late complications after IAC included
affected eyeball volume reduction, subretinal hemorrhage, vitreous hemorrhage,
vitreous opacity, cataractous len, and choroidal vascular ischemia.
PMID- 28415601
TI - Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia.
AB - GATA3 polymorphisms were reported to be significantly associated with
susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by
impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism
located around in the tissue-specific enhancer, and significantly associated with
GATA3 expression. Although the regulatory network of GATA3 has been well reported
in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus
conducted genome-wide gene expression association analyses to reveal expression
associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL
patients, 173 candidates were identified to be significantly associated with
GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and
well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit
tissue-specific and subtype-specific association with GATA3. Through
overexpression and down-regulation of GATA3 in leukemia cell lines, several
reported and novel GATA3 regulated genes were validated. Moreover, association of
GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which
locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may
be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL
to impact leukemogenesis through epigenetic regulation.
PMID- 28415603
TI - Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors.
AB - Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is
a promising target for anticoagulation drugs. Three oral FXa inhibitors have been
approved by FDA for treating thrombotic diseases. In this study, 43 novel
compounds were synthesized anthranilamide-based FXa inhibitors aiming to
ameliorate the toxicity of traditional FXa inhibitors in clinic. The data
indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable
FXa inhibitory activity and excellent selectivity over thrombin in vitro.
Selected compounds also exhibited anticoagulant activities in vitro consequently
and were potent novel anti-coagulators in further.
PMID- 28415602
TI - ERRF sensitizes ERBB2-positive breast cancer cells to lapatinib treatment likely
by attenuating MCL1 and ERBB2 expression.
AB - Previously we found that the estrogen receptor (ER) related factor ERRF regulates
cell proliferation and tumor growth, and its expression is positively associated
with ER status and better survival but inversely associated with ERBB2 (also
named HER2) status in breast cancer. Here we report that ERRF also plays an
important role in the response of ERBB2-positive breast cancer cells to
lapatinib, a dual tyrosine kinase inhibitor that interrupts the ERBB2 and EGFR
pathway. In ERBB2-positive breast cancer cell lines, lower levels of ERRF
expression correlated with lapatinib resistance, restoration of ERRF expression
in lapatinib-resistant cell lines JIMT-1 and MDA-MB-453 enhanced their lapatinib
responses, and knockdown of ERRF in lapatinib sensitive cell lines BT-474 and SK
BR-3 caused lapatinib resistance. ERRF-enhanced lapatinib sensitivity was also
confirmed in xenograft tumors of JIMT-1 cells. In patients with ERBB2-positive
breast cancer, higher level of ERRF expression correlated with both pathologic
complete response (pCR) to lapatinib and better survival. Mechanistically, ERRF
expression in resistant cells promoted lapatinib-induced apoptosis by attenuating
MCL1 and ERBB2 expression. These results suggest that ERRF plays an important
role in lapatinib response of ERBB2-positive breast cancer, and further study of
ERRF could lead to improved prediction and sensitivity of lapatinib response.
PMID- 28415605
TI - KIFC1 is essential for acrosome formation and nuclear shaping during
spermiogenesis in the lobster Procambarus clarkii.
AB - In order to study the function of kinesin-14 motor protein KIFC1 during
spermatogenesis of Procambarus clarkii, the full length of kifc1 was cloned from
testes cDNA using Rapid-Amplification of cDNA Ends (RACE). The deduced KIFC1
protein sequence showed the highest similarity between Procambarus clarkii and
Eriocheir senensis (similarity rate as 64%). According to the results of in situ
hybridization (ISH), the kifc1 mRNA was gathered in the acrosome location above
nucleus in the mid- and late-stage spermatids. Immunofluorescence results were
partly consistent with the ISH in middle spermatids, while in the late spermatids
the KIFC1 was distributed around the nucleus which had large deformation and
formed four to six nuclear arms. In the mature sperm, KIFC1 and microtubules were
distributed around the sperm, playing a role in maintaining the sperm morphology
and normal function. Overexpression of P. clarkii kifc1 in GC1 cells for 24 hours
resulted in disorganization of microtubules which changed the cell morphology
from circular and spherical into fusiform. In addition, the overexpression also
resulted in triple centrosomes during mitosis which eventually led to cell
apoptosis. RNAi experiments showed that decreased KIFC1 protein levels resulted
in total inhibition of spermatogenesis, with only mature sperm found in the RNAi
testis, implying an indispensable role of KIFC1 during P. clarkii spermiogenesis.
PMID- 28415604
TI - Inhibiting G protein betagamma signaling blocks prostate cancer progression and
enhances the efficacy of paclitaxel.
AB - Aberrant activation of G protein-coupled receptors (GPCRs) is implicated in
prostate cancer progression, but targeting them has been challenging because
multiple GPCRs are involved in cancer progression. In this study, we tested the
effect of blocking signaling via a hub through which multiple GPCRs converge -
the G-protein Gbetagamma subunits. Inhibiting Gbetagamma signaling in several
castration-resistant prostate cancer cell lines (i.e. PC3, DU145 and 22Rv1),
impaired cell growth and migration in vitro, and halted tumor growth and
metastasis in nude mice. The blockade of Gbetagamma signaling also diminished
prostate cancer stem cell-like activities, by reducing tumorsphere formation in
vitro and tumor formation in a limiting dilution assay in nude mice. Furthermore,
Gbetagamma blockade enhanced the sensitivity of prostate cancer cells to
paclitaxel treatment, both in vitro and in vivo. Together, our results identify a
novel function of Gbetagamma in regulating prostate cancer stem-cell-like
activities, and demonstrate that targeting Gbetagamma signaling is an effective
approach in blocking prostate cancer progression and augmenting response to
chemotherapy.
PMID- 28415606
TI - TAZ induces lung cancer stem cell properties and tumorigenesis by up-regulating
ALDH1A1.
AB - Recent studies suggest that lung cancer stem cells (CSCs) may play major roles in
lung cancer. Therefore, identification of lung CSC drivers may provide promising
targets for lung cancer. TAZ is a transcriptional co-activator and key downstream
effector of the Hippo pathway, which plays critical roles in various biological
processes. TAZ has been shown to be overexpressed in lung cancer and involved in
tumorigenicity of lung epithelial cells. However, whether TAZ is a driver for
lung CSCs and tumor formation in vivo is unknown. In addition, the molecular
mechanism underlying TAZ-induced lung tumorigenesis remains to be determined. In
this study, we provided evidence that constitutively active TAZ (TAZ-S89A) is a
driver for lung tumorigenesis in vivo in mice and formation of lung CSC. Further
RNA-seq and qRT-PCR analysis identified Aldh1a1, a well-established CSC marker,
as critical TAZ downstream target and showed that TAZ induces Aldh1a1
transcription by activating its promoter activity through interaction with the
transcription factor TEAD. Most significantly, inhibition of ALDH1A1 with its
inhibitor A37 or CRISPR gene knockout in lung cancer cells suppressed lung
tumorigenic and CSC phenotypes in vitro, and tumor formation in mice in vivo. In
conclusion, this study identified TAZ as a novel inducer of lung CSCs and the
first transcriptional activator of the stem cell marker ALDH1A1. Most
significantly, we identified ALDH1A1 as a critical meditator of TAZ-induced
tumorigenic and CSC phenotypes in lung cancer. Our studies provided preclinical
data for targeting of TAZ-TEAD-ALDH1A1 signaling to inhibit CSC-induced lung
tumorigenesis in the future.
PMID- 28415607
TI - Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA
hypermethylation reversal in leukemia cells.
AB - Thymoquinone (TQ), a bioactive constituent of the volatile oil of Monarda
fistulosa and Nigella sativa, possesses cancer-specific growth inhibitory
effects, but the underlying molecular mechanisms remain largely elusive. We
propose that TQ curbs cancer cell growth through dysfunction of DNA
methyltransferase 1 (DNMT1). Molecular docking analysis revealed that TQ might
interact with the catalytic pocket of DNMT1 and compete with co-factor SAM/SAH
for DNMT1 inhibition. In vitro inhibitory assays showed that TQ decreases DNMT1
methylation activity in a dose-dependent manner with an apparent IC50 of 30 nM.
Further, exposure of leukemia cell lines and patient primary cells to TQ resulted
in DNMT1 downregulation, mechanistically, through dissociation of Sp1/NFkB
complex from DNMT1 promoter. This led to a reduction of DNA methylation, a
decrease of colony formation and an increase of cell apoptosis via the activation
of caspases. In addition, we developed and validated a sensitive and specific LC
MS/MS method and successfully detected a dynamic change of TQ in mouse plasma
after administration of TQ through the tail vein, and determined a tolerable dose
of TQ to be 15 mg/kg in mouse. TQ administration into leukemia-bearing mice
induced leukemia regression, as indicated by the reversed splenomegaly and the
inhibited leukemia cell growth in lungs and livers. Our study for the first time
demonstrates that DNMT1-dependent DNA methylation mediates the anticancer actions
of TQ, opening a window to develop TQ as a novel DNA hypomethylating agent for
leukemia therapy.
PMID- 28415608
TI - Collagen type IV alpha 1 (COL4A1) and collagen type XIII alpha 1 (COL13A1)
produced in cancer cells promote tumor budding at the invasion front in human
urothelial carcinoma of the bladder.
AB - Current knowledge of the molecular mechanism driving tumor budding is limited.
Here, we focused on elucidating the detailed mechanism underlying tumor budding
in urothelial cancer of the bladder. Invasive urothelial cancer was
pathologically classified into three groups as follows: nodular, trabecular, and
infiltrative (tumor budding). Pathohistological analysis of the orthotopic tumor
model revealed that human urothelial cancer cell lines MGH-U3, UM-UC-14, and UM
UC-3 displayed typical nodular, trabecular, and infiltrative patterns,
respectively. Based on the results of comprehensive gene expression analysis
using microarray (25 K Human Oligo chip), we identified two collagens, COL4A1 and
COL13A1, which may contribute to the formation of the infiltrative pattern.
Visualization of protein interaction networks revealed that proteins associated
with connective tissue disorders, epithelial-mesenchymal transition, growth
hormone, and estrogen were pivotal factors in tumor cells. To evaluate the
invasion pattern of tumor cells in vitro, 3-D collective cell invasion assay
using Matrigel was performed. Invadopodial formation was evaluated using Gelatin
Invadopodia Assay. Knockdown of collagens with siRNA led to dramatic changes in
invasion patterns and a decrease in invasion capability through decreased
invadopodia. The in vivo orthotopic experimental model of bladder tumors showed
that intravesical treatment with siRNA targeting COL4A1 and COL13A1 inhibited the
formation of the infiltrative pattern. COL4A1 and COL13A1 production by cancer
cells plays a pivotal role in tumor invasion through the induction of tumor
budding. Blocking of these collagens may be an attractive therapeutic approach
for treatment of human urothelial cancer of the bladder.
PMID- 28415609
TI - Identification of driver modules in pan-cancer via coordinating coverage and
exclusivity.
AB - It is widely accepted that cancer is driven by accumulated somatic mutations
during the lifetime of an individual. Cancer mutations may target relatively
small number of cell functional modules. The heterogeneity in different cancer
patients makes it difficult to identify driver mutations or functional modules
related to cancer. It is biologically desired to be capable of identifying cancer
pathway modules through coordination between coverage and exclusivity. There have
been a few approaches developed for this purpose, but they all have limitations
in practice due to their computational complexity and prediction accuracy. We
present a network based approach, CovEx, to predict the specific patient oriented
modules by 1) discovering candidate modules for each considered gene, 2)
extracting significant candidates by harmonizing coverage and exclusivity and, 3)
further selecting the patient oriented modules based on a set cover model.
Applying CovEx to pan-cancer datasets spanning 12 cancer types collecting from
public database TCGA, it demonstrates significant superiority over the current
leading competitors in performance. It is published under GNU GENERAL PUBLIC
LICENSE and the source code is available at:
https://sourceforge.net/projects/cancer-pathway/files/.
PMID- 28415610
TI - The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS
accumulation and activation of FOXO3 in neuroblastoma.
AB - Neuroblastoma is the most frequent extra-cranial solid tumor in children with
still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as
a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477
induces death in neuroblastoma cells independent of PKB-activation status and
stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that
finally leads to cell death associated with mitotic catastrophe. Autophagy is
critical for MG-2477-induced death and is regulated by the BH3-only protein
PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby
displaces and activates the autophagy-regulator BECN1/beclin1. Knockdown of NOXA
or overexpression of its pro-survival binding partners MCL1 and BCLXL counteracts
MG-2477-induced cell death. MG-2477 also rapidly induces the repression of the
anti-apoptotic protein Survivin, which promotes autophagy and cell death. We
further observed the accumulation of reactive oxygen species (ROS) that triggers
autophagy induction suggesting a change of the PI3 kinase-III/BECN1 complex and
activates the transcription factor FOXO3, which contributes to final cell death
induction. The combined data suggest that MG-2477 induces a sequential process of
ROS-accumulation, autophagy and FOXO3-activation that leads to cell death in
neuroblastoma cells.
PMID- 28415616
TI - Z-ligustilide restores tamoxifen sensitivity of ERa negative breast cancer cells
by reversing MTA1/IFI16/HDACs complex mediated epigenetic repression of ERa.
AB - Emerging evidence indicates epigenetic modification represses estrogen receptor
alpha (ERalpha) and contributes to the resistance to tamoxifen in aggressive
ERalpha-negative (ERalpha-) breast cancer. Z-ligustilide is a major compound in
Radix Angelica sinensis, an herb from traditional Chinese medicine (TCM) most
frequently prescribed for breast cancer. However, the role of Z-ligustilide in
ERalpha- breast cancer and epigenetic modification remains largely unknown.
Herein we showed, for the first time, that Z-ligustilide restored the growth
inhibition of tamoxifen on ERalpha- breast cancer cells. Apoptosis and S and G2/M
phases cell cycle arrest were induced by combinatorial Z-ligustilide and
tamoxifen. Importantly, Z-ligustilide reactivated the ERalpha expression and
transcriptional activity, which is proved to be indispensable for restoring the
sensitivity to tamoxifen. Interestingly, Z-ligustilide increased Ace-H3 (lys9/14)
enrichment in the ERalpha promoter. Moreover, Z-ligustilide dramatically reduced
the enrichment of metastasis-associated protein 1 (MTA1) as well as IFN-gamma
inducible protein 16 (IFI16) and histone deacetylases (HDACs) onto the ERalpha
promoter. Meanwhile, Z-ligustilide downregulated MTA1, IFI16 and HDACs, which
caused destabilization of the corepressor complex. Collectively, our study not
only highlights Z-ligustilide as a novel epigenetic modulator, but also opens new
possibilities from TCM for treating aggressive tamoxifen-resistant breast cancer.
PMID- 28415618
TI - Circular RNA alterations are involved in resistance to avian leukosis virus
subgroup-J-induced tumor formation in chickens.
AB - Avian leukosis virus subgroup (ALV-J) is an oncogenic neoplasm-inducing
retrovirus that causes significant economic losses in the poultry industry.
Recent studies have demonstrated circular RNAs (circRNAs) are implicated in
pathogenic processes; however, no research has indicated circRNAs are involved in
resistance to disease. In this study, over 1800 circRNAs were detected by circRNA
sequencing of liver tissues from ALV-J-resistant (n = 3) and ALV-J-susceptible
chickens (n = 3). 32 differentially expressed circRNAs were selected for
analyzing including 12 upregulated in ALV-J-resistant chickens and 20 upregulated
in ALV-J-susceptible chickens, besides, the top five microRNAs (miRNAs) for 12
upregulated circRNAs in ALV-J-resistant chickens were analyzed. Gene ontology and
KEGG pathway analyses were performed for miRNA target genes, the predicted genes
were mainly involved in immune pathways. This study provides the first evidence
that circRNA alterations are involved in resistance to ALV-J-induced tumor
formation. We propose circRNAs may help to mediate tumor induction and
development in chickens.
PMID- 28415619
TI - Association of two microRNA polymorphisms miR-27 rs895819 and miR-423 rs6505162
with the risk of cancer.
AB - Many studies have been conducted to investigate the association between miR-27
rs895819 A > G and miR-423 rs6505162 C > A and cancer risk; however, the results
are not consistent. In order to acquire a more precise assessment of the
correlation, we performed this meta-analysis. We searched PubMed, EMBASE and Web
of Science databases to identify eligible studies. Pooled odds ratios (ORs) and
95% confidence intervals (CIs) were applied to evaluate the correlation of these
two microRNA polymorphisms with cancer risk. Forty-five eligible studies from
thirty-five articles were included in our analysis. The results showed that
rs895819 was associated with a decreased cancer risk in Caucasians (AG vs. AA: OR
= 0.87, 95% CI = 0.79-0.96; GG+AG vs. AA: OR = 0.89, 95% CI = 0.81-0.98). When
grouped by ethnicity, an increased risk was observed in colorectal cancer (G vs.
A: OR = 1.19, 95% CI = 1.08-1.32; GG vs. AA: OR = 1.58, 95% CI = 1.28-1.96; GG
vs. AG+AA: OR = 1.58, 95% CI = 1.29-1.93), while a decreased risk was found in
breast cancer (G vs. A: OR = 0.93, 95% CI = 0.87-0.99; GG+AG vs. AA: OR = 0.91,
95% CI = 0.83-0.99). For rs6505162, a significantly decreased cancer risk was
observed in lung cancer under all five genetic models. To summarize, our results
indicated that rs895819 was a protective factor for cancer in Caucasians and
could increase colorectal cancer risk but decrease breast cancer risk. Moreover,
rs6505162 was a protective factor for lung cancer.
PMID- 28415621
TI - USP22 maintains gastric cancer stem cell stemness and promotes gastric cancer
progression by stabilizing BMI1 protein.
AB - Increased ubiquitin-specific protease 22 (USP22) has been associated with poor
prognosis in several cancers including gastric cancer. However, the role of USP22
in gastric tumorigenesis is still unclear. Gastric cancer stem cells have been
identified and shown to correlate with gastric cancer initiation and metastasis.
In this study, we found that silencing of USP22 inhibited proliferation of
gastric cancer cells and suppressed the cancer stem cell spheroid formation in
serum-free culture. Furthermore, cancer stem cell markers, such as CD133, SOX2,
OCT4 and NANOG were down-regulated. Additionally, knockdown of USP22 inhibited
gastric cancer xenografts growth. Our analysis of TCGA database indicated that
BMI1 overexpression may predict gastric cancer patient survival, and TAT-BMI1
proteins reversed the USP22 knockdown-mediated decreased in cancer stem cell
properties, and elevated the expression of stemness-associated genes.
Furthermore, we found that overexpression of USP22 stabilized the BMI1 protein in
gastric cancer cells. Taken together, our study demonstrates that USP22 is
indispensable for gastric cancer stem cell self-renewal through stabilization of
BMI1. These results may provide novel approaches to the theranostics of gastric
cancer in the near future.
PMID- 28415624
TI - Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular
smooth muscle cell through PI3K/AKT/AEG-1 signaling.
AB - To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG
1) have been involved in the proliferation, migration and morphological changes
of vascular smooth muscle cells. However, the potential relationship of HIF-1a
AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported.
In the present study, in-vitro assays were utilized to explore the potential
impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a
expression was up-regulated in the media of thoracic aortic dissection tissues as
compared with normal aortic tissues, and was associated with increased apoptotic
SMCs and decreased AEG-1 expression. Mechanically, hypoxia promoted the
expression of HIF-1a by PI3K-AKT pathway in HASMCs; HIF-1a further suppressed the
expressions of AEG-1, a-SMA and SM22a, and promoted osteopontin (OPN) expression.
Functionally, HIF-1a inhibited the proliferation and migration of HASMCs.
However, si-HIF-1a or Akt inhibitor abrogated HIF-1a-mediated related expressions
and biological effects above. In conclusion, HIF-1a induces HASMC phenotype
switch, and closely related to PI3K/AKT and AEG-1 signaling, which may provide
new avenues for the prevention and treatment of aortic dissection diseases.
PMID- 28415625
TI - Coroglaucigenin enhances the radiosensitivity of human lung cancer cells through
Nrf2/ROS pathway.
AB - Seven cardenolides isolated from the ethanol extract of the stems of Calotropis
gigantea were evaluated in vitro against human cancer cells and the structure
activity relationships were discussed. The results demonstrated that a compound,
named CGN (coroglaucigenin), had better anti-proliferative activity with the IC50
value less than 6 MUM among these compounds. Further, we found that CGN displayed
much lower cytotoxicity to normal lung epithelial cells (BEAS-2B) than cancer
cells (A549). Especially, our results demonstrated that treatment with CGN (1
MUM) combined with X-ray irradiation induced higher radiosensitivity in human
lung cancer cells (A549, NCI-H460, NCI-H446) but not in BEAS-2B. The expression
levels of nuclear transcription factor Nrf2 and Nrf2-driven antioxidant molecule
NQO-1 reduced in A549 cells after combined treatment compared to the radiation
only. However, CGN had no toxicity and the levels of antioxidant molecules
expression were higher in BEAS-2B cells when given the similar treatment as A549
cells. These results suggest that CGN is a very promising potential sensitizer
for cancer radiotherapy, which not only inhibits the proliferation of cancer
cells but also enhances the radiosensitivity of cancer cells through suppressing
the expression of antioxidant molecules while there is no influence for normal
cells.
PMID- 28415626
TI - Hematopoietic stem/progenitor cells are less prone to undergo apoptosis than
lymphocytes despite similar DNA damage response.
AB - Hematopoietic stem/progenitor CD34+ cells (HSPC) give rise to all types of blood
cells and represent a key cellular target for origination of leukemia. Apoptosis
and repair of DNA double strand breaks (DSB) are vital processes in
leukemogenesis. High doses of ionizing radiation are the best known agent that
induces leukemia, but less is known about the leukemogenic potential of low
doses. While umbilical cord blood (UCB) serves as a valuable source of the HSPC
for both research and clinics, the data on DNA damage response and apoptosis in
UCB HSPC are very limited. We have studied apoptosis and DSB in the UCB-derived
CD34+HSPC and CD34- lymphocytes at different time points post-irradiation with
low and therapeutic doses of gamma-rays. DSB were enumerated with gammaH2AX foci
using imaging flow cytometry. Different stages of apoptosis were analyzed using
Annexin/7-AAD assay and gammaH2AX pan-staining by flow cytometry and imaging flow
cytometry, respectively. Our results have consistently shown significantly higher
resistance of CD34+ stem/progenitor cells to endogenous and radiation induced
apoptosis as compared to CD34- lymphocytes. At the same time, no statistically
significant difference was found in DSB repair between HSPC and lymphocytes as
enumerated by the gammaH2AX foci. To conclude, we show for the first time that
hematopoietic stem/progenitor cells are less prone to undergo apoptosis than
lymphocytes what may be accounted for higher expression of anti-apoptotic
proteins in CD34+ cells but was unlikely dealt with DSB repair.
PMID- 28415627
TI - Importance of the plasma soluble HLA-G levels for prognostic stratification with
traditional prognosticators in colorectal cancer.
AB - An increased peripheral soluble HLA-G (sHLA-G) expression has been observed in
various malignancies while its prognostic significance was rather limited. In
this study, the prognostic value of plasma sHLA-G in 178 colorectal cancer (CRC)
patients was investigated. sHLA-G levels were analyzed by specific enzyme-linked
immunosorbent assay. Data showed sHLA-G levels were significantly increased in
CRC patients compared with normal controls (36.8 U/ml vs 25.4 U/ml, p = 0.009).
sHLA-G in the died were obviously higher than that of alive CRC patients (46.8
U/ml vs 27.4 U/ml, p = 0.012). Patients with sHLA-G above median levels (>= 36.8
U/ml, sHLA-Ghigh) had a significantly shorter survival time than those with sHLA
Glow (< 36.8 U/ml, p < 0.001), and sHLA-G could be an independent prognostic
factor for CRC patients. With stratification of clinical parameters in survival
by sHLA-Glow and sHLA-Ghigh, sHLA-G exhibited a significant predictive value for
CRC patients of the female (p = 0.036), the elder (p = 0.009), advanced tumor
burden (T3 + 4, p = 0.038), regional lymph node status (N0, p = 0.041), both
metastasis status (M0, p = 0.014) and (M1, p=0.018), and clinical stage (I + II,
p = 0.018), respectively. Summary, our data demonstrated for the first time that
sHLA-G levels is an independent prognosis factor and improves the prognostic
stratification offered by traditional prognosticators in CRC patients.
PMID- 28415628
TI - Gut microbiota drives the attenuation of dextran sulphate sodium-induced colitis
by Huangqin decoction.
AB - The gut microbiota, including probiotics and pathogenic microorganisms, is
involved in ulcerative colitis (UC) by regulating pathogenic microorganisms and
the production of intestinal mucosal antibodies. Huangqin decoction (HQD), a
traditional Chinese formula chronicled in the Shanghan lun, has been recognized
as an effective drug for UC, owing to its anti-inflammatory and anti-oxidative
properties. In the present study, we investigated whether HQD ameliorates dextran
sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota.
We found that HQD significantly inhibited colitis, alleviating the loss of body
weight, disease activity index, colon shortening, tissue injury, and inflammatory
cytokine changes induced by DSS treatment. Principal component analysis and
principal co-ordinate analysis showed an obvious difference among the groups,
with increased diversity in the DSS and DSS+HQD groups. Linear discriminant
analysis effect size was used to determine differences between the groups. The
relative abundance of Lactococcus was higher in the DSS+HQD group than in the DSS
group, whereas Desulfovibrio and Helicobacter were decreased. Furthermore, the
protective effect of HQD was attenuated only in antibiotic-treated mice. In
conclusion, our results suggest that HQD could ameliorate DSS-induced
inflammation through alteration of the gut microbiota.
PMID- 28415629
TI - A(H1N1)pdm09 influenza infection: vaccine inefficiency.
AB - The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus,
began in North America at 2009. Since then, the World Health Organization (WHO)
recommended integration of the swine-based virus A/California/07/2009 strain in
yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in
subsequent years. The reasons for this are currently unknown. During the 2015
2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza
virus infection in Israel. Our phylogenetic analysis indicated that the
circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed
from the vaccinating strain, with approximately 18 amino acid differences found
between the circulating strains and the immunizing A/California/07/2009 strain.
Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer
against the A/California/07/2009 vaccinating strain as compared to the
circulating Israeli strains. We thus suggest that the current vaccination was not
sufficiently effective and propose inclusion of the current circulating
A(H1N1)pdm09 influenza viruses in the annual vaccine composition.
PMID- 28415630
TI - Resveratrol alleviates FFA and CCl4 induced apoptosis in HepG2 cells via
restoring endoplasmic reticulum stress.
AB - Cell apoptosis often induces inflammation and injury in the liver, with
endoplasmic reticulum (ER) stress as the most possible reason. Resveratrol (RSV)
has been shown to prevent hepatic steatosis and alleviate apoptosis, however, the
exact mechanisms underlying the effects still need to be explored. Here we co
cultured HepG2 cells with free fatty acid (FFA) solution (oleic acid: palmitic
acid = 2:1) and then exposed to a carbon tetrachloride (CCl4) solution to induce
apoptosis. To evaluate the therapeutic effects, RSV (2.5 MUM, 5 MUM, 10 MUM) was
added to the cells. Results showed that HepG2 cells co-cultured with FFA
exhibited lipid infiltration and were susceptible to apoptosis upon exposure to
the CCl4 solution. The expression of molecules related to apoptosis (Caspases,
Bcl-2/Bax) and ER stress (GRP78, IRE1, ATF6, PERK, et al.) was all significantly
decreased upon RSV treatment. We further inhibited GRP78 by siRNA, results showed
that the anti-apoptotic effect of RSV still maintained under GRP78 siRNA
condition. Our data demonstrated that lipid accumulated HepG2 cells were
susceptible to injury, and RSV could improve apoptosis in FFA and CCl4 stressed
cells, which partially via restoring ER function.
PMID- 28415631
TI - LncRNA HOTAIR acts a competing endogenous RNA to control the expression of notch3
via sponging miR-613 in pancreatic cancer.
AB - Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though
studies have implicated the roles of microRNAs in pancreatic cancer progression,
little is known about the role of miR-613 in pancreatic cancer. In the present
study, the expression of miR-613 was down-regulated in pancreatic cancer tissues
and cancer cell lines. Down-regulation of miR-613 was positively correlated with
tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall
survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed
cell proliferation, invasion and migration, and induced cell apoptosis and cell
cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis,
luciferase reporter assay and rescue experiments showed that notch3 was a direct
target of miR-613. MiR-613 was inversely correlated with notch3 expression in
pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA
(HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell
lines, and HOTAIR suppressed the expression of miR-613 via functioning as a
competing endogenous RNA. In vivo studies showed that stable overexpression of
miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the
expression of notch3. In conclusion, these results suggest that HOTAIR functions
as a competing endogenous RNA to regulate notch3 expression via sponging miR-613
in pancreatic cancer.
PMID- 28415632
TI - The combined effect of USP7 inhibitors and PARP inhibitors in hormone-sensitive
and castration-resistant prostate cancer cells.
AB - PURPOSE OF THE STUDY: Reduced levels of the tumor suppressor protein CCDC6
sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of
CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the
androgen receptor (AR) stability. Here, we correlated the expression levels of
CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the
efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel
therapeutic option in advanced prostate cancer.Experimental techniques: PC cells
were exposed to USP7 inhibitor, P5091, together with cycloheximide, to
investigate the turnover of the USP7 substrates, AR and CCDC6. As outcome of the
AR downregulation, transcription targets of AR and its variant V7 were examined
by qPCR. As a result of CCDC6 degradation, the induction of PARP inhibitors
sensitivity was evaluated by analyzing PC cells viability and foci formation. We
scored and correlated CCDC6 and USP7 expression levels in a prostate cancer
tissue microarray (TMA). RESULTS: P5091 accelerated the degradation of AR and V7
isoform affecting PSA, UBE2C, CDC20 transcription and PC cells proliferation.
Moreover, P5091 accelerated the degradation of CCDC6 sensitizing the cells to
PARP-inhibitors, that acted sinergistically with genotoxic agents. The
immunohistochemical analysis of both CCDC6 and USP7 proteins exhibited
significant correlation for the intensity of staining (p <= 0.05).Data
interpretation: Thus, CCDC6 and USP7 represent predictive markers for the
combined treatment of the USP7-inhibitors and PARP-inhibitors in advanced
prostate cancer.
PMID- 28415633
TI - A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic
adenoid cystic carcinoma.
AB - PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a
confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient
treated with vorinostat in a prior phase 1 trial, we initiated this phase 2
trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles.
The primary objective was to evaluate response rate (RR). Exploratory studies
included whole exome sequencing (WES) of selected patients. RESULTS: Thirty
patients were enrolled. Median age of patients was 53 years (range 21-73). Median
number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3),
oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the
only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven
patients were dose reduced secondary to drug-related AEs. Two patients had a
partial response (PR), with response durations of 53 and 7.2 months. One patient
had a minor response with a decrease in ascites (for 19 cycles). Stable disease
was the best response in 27 patients. Targeted and WES of 8 patients in this
trial identified mutations in chromatin remodeling genes highlighting the role of
the epigenome in ACC. CONCLUSION: Vorinostat demonstrated efficacy in patients
with ACC supporting the inclusion of HDACi in future studies to treat ACC.
PMID- 28415634
TI - A meta-analysis of randomized controlled trials comparing the efficacy and safety
of anastrozole versus tamoxifen for breast cancer.
AB - Whether anastrozole has superior effects to tamoxifen for breast cancer remains
controversial. Therefore, we conducted this meta-analysis of randomized
controlled trials (RCTs) to compare the efficacy and safety of anastrozole versus
tamoxifen as adjuvant therapy in breast cancer. A systematic literature search of
PubMed, Web of Science, Embase, and Cochrane library were performed to evaluate
the survival benefits and toxicity profiles of patients with breast cancer who
were treated with anastrozole or tamoxifen. The main outcome measures included
disease-free survival (DFS), recurrence-free survival (RFS), overall survival
(OS), overall response rate (ORR), and adverse events. Hazard ratios (HRs) or
risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a fixed
effects model or random-effects model. Nine RCTs with a total of 15,300 patients
met the inclusion criteria and were included in this meta-analysis. Pooled
estimates suggested that, anastrozole was associated with a significantly
improvement in DFS (HR=0.72, 95%CI: 0.55-0.94; P=0.016), and ORR (RR=1.21, 95%
CI: 1.05-1.39; P=0.009) than tamoxifen. But it did not prolong OS (HR=0.96,
95%CI: 0.77-1.21; P=0.751). Compared with tamoxifen, anastrozole induced a higher
incidence of arthralgia (RR=1.55, 95%CI: 1.20-1.99; P=0.001) and bone pain
(RR=1.31, 95%CI: 1.05-1.62; P=0.015), as well as a lower incidence of vaginal
bleeding (RR=0.51, 95%CI: 0.28-0.93; P=0.029), vaginal discharge (RR=0.31, 95%CI:
0.12-0.82; P=0.017), and thromboembolic events (RR=0.39, 95%CI: 0.28-0.55;
P<0.001). Based on the current evidence, patients with breast cancer would
benefit from the anastrozole treatment.
PMID- 28415636
TI - Comparison of combined leflunomide and low-dose corticosteroid therapy with full
dose corticosteroid monotherapy for progressive IgA nephropathy.
AB - IgA nephropathy is the most common primary glomerulonephritis and one of the
leading causes of end-stage renal disease. We performed a randomized, controlled,
prospective, open-label trial to determine whether leflunomide combined with low
dose corticosteroid is safe and effective for the treatment of progressive IgA
nephropathy, as compared to full-dose corticosteroid monotherapy. Biopsy-proved
primary IgA nephropathy patients with an estimated glomerular filtration rate >=
30 ml/min/1.73m2 and proteinuria >=1.0 g/24h were randomly assigned to receive
leflunomide+low-dose corticosteroid (leflunomide group; n = 40) or full-dose
corticosteroid (corticosteroids group; n = 45). The primary outcome was renal
survival; secondary outcomes were proteinuria and adverse events. After 12 months
of treatment and an average follow-up of 88 months, 11.1% vs. 7.5% of patients
reached end-stage renal disease and 20% versus 10% of patients had a >= 50%
increase in serum creatinine in the corticosteroids and leflunomide groups,
respectively. Kaplan-Meier analysis did not reveal a between-group difference in
these outcomes. Decreases in 24-hour proteinuria were similar in the two groups
during the treatment period, but a more marked reduction was observed during
follow-up in the leflunomide group. Although the incidence of adverse events was
similar in the two groups, serious adverse events were observed only in the
corticosteroid group. Thus, leflunomide combined with low-dose corticosteroid is
at least as effective as corticosteroid alone for the treatment of progressive
IgA nephropathy, and showed a greater reduction of proteinuria during long-term
follow-up and fewer severe adverse events.
PMID- 28415635
TI - Role of EZH2 in cancer stem cells: from biological insight to a therapeutic
target.
AB - Epigenetic modifications in cancer stem cells largely result in phenotypic and
functional heterogeneity in many solid tumors. Increasing evidence indicates that
enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb repressor
complex 2, is highly expressed in cancer stem cells of numerous malignant tumors
and has a critical function in cancer stem cell expansion and maintenance. Here,
we review up-to-date information regarding EZH2 expression patterns, functions,
and molecular mechanisms in cancer stem cells in various malignant tumors and
discuss the therapeutic potential of targeting EZH2 in tumors.
PMID- 28415638
TI - Altered long non-coding RNAs predict worse outcome in osteosarcoma patients:
evidence from a meta-analysis.
AB - Long non-coding RNAs (lncRNAs) are emerging as promising prognostic biomarkers in
an expanding list of malignant neoplasms. Here, we sought to investigate the
strength of associations between lncRNA signatures and clinical outcomes in
osteosarcoma. We conducted a systematic search of the online databases from
inception to July 2016. Hazard ratios (HRs) with corresponding 95% confidence
intervals (CIs) for the primary endpoints of overall survival (OS), progression
free survival (PFS) or event-free survival (EFS) were extracted and meta
analyzed. Our results manifested that altered lncRNAs expression was markedly
associated with worse OS (univariate analysis: HR = 3.20, 95% CI: 2.42-4.24, P =
0.000; multivariate analysis: HR = 2.66, 95% CI: 1.92-3.69, P = 0.000), PFS (HR =
2.05, 95% CI: 1.32-3.18, P = 0.001) and EFS (HR = 4.37, 95% CI: 1.64-11.66, P =
0.003) times among osteosarcoma patients. In the pooled analyses stratified by
clinicopathological features, levels of lncRNAs were closely correlated with
tumor size (pooled P = 0.001), tumor stage (pooled P = 0.003), and distant
metastasis (pooled P = 0.002) in osteosarcoma. The results obtained in our work
suggest that altered lncRNA signatures predict unfavorable clinical outcomes and
are acceptable to be potential prognostic biomarkers in forecasting prognosis of
osteosarcoma.
PMID- 28415639
TI - Epithelial-to-mesenchymal transition in the development of endometriosis.
AB - Endometriosis, an estrogen-dependent chronic gynecological disease, is common in
reproductive-age women and profoundly affects their life quality. Although
various pathogenic theories have been proposed, the origin of endometriosis
remains unclear. Epithelial to mesenchymal transition (EMT) is a process that
epithelial cells lose polarized organization of the cytoskeleton and cell-to-cell
contacts, acquiring the high motility of mesenchymal cells. These changes are
thought to be prerequisites for the original establishment of endometriotic
lesions. However, no study exactly indicates which type of EMT occurs in
endometriosis. In this review, we conclude that two different types of EMT may
participate in this disease. Besides, two stimulating signals, hypoxia and
estrogen, can through different pathways to activate the EMT process in
endometriosis. Those pathways involve many cellular factors such as TGF-beta and
Wnt, ultimately leading to cell proliferation and migration. As infertility is
becoming a serious and intractable issue for women, EMT, during the implantation
process, is gaining attention. In this review, we will describe the known
functions of EMT in endometriosis, and suggest further studies that may aid in
the development of medical therapy.
PMID- 28415640
TI - Accuracy of the urine UCA1 for diagnosis of bladder cancer: a meta-analysis.
AB - Urine UCA1 has been reported as a potential novel diagnostic biomarker for
bladder cancer in several studies, but their results are inconsistent. As a
result of this, a diagnostic meta-analysis to assess the diagnostic performance
of urine UCA1 in detecting bladder cancer was conducted. A systematic electronic
and manual search was performed for relevant literatures through PubMed, Cochrane
library, Chinese Wan Fang and the China National Knowledge Infrastructure (CNKI)
databases up to December 30, 2016. The quality of the studies included in this
meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy
Studies (QUADAS-2) tool. All analyses were conducted using stata12.0 software.
Six studies collectively included 578 bladder cancer patients and 562 controls
met the eligible criteria. The overall diagnostic accuracy was measured by the
following: sensitivity 0.81 (95% CI = 0.75-0.86), specificity 0.86 (95% CI = 0.73
0.93), positive likelihood ratio 5.85 (95% CI = 2.72-12.57), negative likelihood
0.22 (95% CI = 0.15-0.32), diagnostic odds ratio 27.01 (95% CI = 8.69-83.97), and
area under the curve 0.88 (95% CI = 0.85-0.91). Meta-regression analysis
suggested that ethnicity significantly accounted for the heterogeneity of
sensitivity. Deeks' funnel plot asymmetry test (P = 0.33) suggested no potential
publication bias. According to our results, urine UCA1 has greater diagnostic
value in diagnosing bladder cancer, however further research studies with more
well-designed and large sample sizes are required to confirm our findings.
PMID- 28415643
TI - New transcriptional-based insights into the pathogenesis of desmoplastic small
round cell tumors (DSRCTs).
AB - To gain new insights into desmoplastic small round cell tumors (DSRCTs) by means
of gene expression profiling (GEP). Formalin-fixed, paraffin-embedded surgical
specimens obtained from seven pretreated DSRCT patients were interrogated using
GEP complemented by immunohistochemistry, a cancer stem cell array, and miRNA in
situ hybridisation, including the combined chimera modules miRNA-200/ZEB1 and
miRNA-34/SLUG. The chimera modules divided the cases into three classes that
respectively recapitulated the traits of mesenchymal epithelial reverse
transition (MErT), epithelial mesenchymal transition (EMT), and hybrid/partial
EMT. This indicates a close correlation between the reprogramming governed by EMT
regulators and DSRCT biology, which was further confirmed by miRNA-21 and is
consistent with the broad morphological spectrum of DSRCTs. Starting from the
miRNA-200/ZEB1 axis, we also found that DSRCTs carry a signature of immunological
ignorance that is not responsive to PD--L1 blockade. Evidence that the up
regulation of miRNA-200 and E-cadherin, and quite a high level of miRNA-21
expression segregate with the MErT supports the idea that, in addition to the
hybrid/partial state, MErT is also enriched in stemness: the androgen-positive
cases, whose stemness traits were confirmed by stem cell arrays, all fell into
these two classes. Our findings also confirmed that tumoral cell PDGFRA
expression correlates with desmoplasia, and demonstrated the co-expression of
PDGFRA and ISLR/Meflin, another marker of pluripotency. Despite the limited
number of cases, these findings provide unexpectedly relevant information
concerning the pathogenesis of DSRCTs, and prove the validity of miRNA-based
chimera circuit modelling in the clinico-pathological setting.
PMID- 28415641
TI - Identification and screening of effective protective antigens for channel catfish
against Streptococcus iniae.
AB - Vaccination is a potential approach for prevention and control of disease in
fish. The use of genetically engineered vaccines is an effective method and a
green intervention to control bacterial infection in aquaculture. However,
efforts to develop these vaccines are limited by the lack of conserved protective
antigens. In this study, three candidate immunogens (Srr, NeuA, and Hsp) of the
pathogenic Streptococcus iniae strain DGX07 isolated from diseased channel
catfish were identified and analyzed. Molecular cloning, expression, and
purification of candidate antigen genes were carried out to obtain the candidate
immunogens in the form of recombinant subunit vaccines. Western blotting was
performed to evaluate immunogenicity in vitro and channel catfish were vaccinated
by intraperitoneal injection and the specific antibody titers and relative
percent of survival were determined to evaluate immune protection in vivo. The
results showed that these three candidate immunogens were expressed correctly as
recombinant proteins fused with His tags, with molecular weights of 70 kDa for
Srr, 86 kDa for NeuA, and 51 kDa for Hsp, respectively. Moreover, each immunogen
was predicted to be located either extracellularly or on the surface of S. iniae,
and were able to offer protection against S. iniae infection in the form of
recombinant subunit vaccines with adjuvant ISA763, especially Srr, with a
relative percent of survival of 70% for Srr, 55% for NeuA, and 50% for Hsp,
respectively.
PMID- 28415644
TI - Long non-coding RNAs in cutaneous melanoma: clinical perspectives.
AB - Metastatic melanoma of the skin has a high mortality despite the recent
introduction of targeted therapy and immunotherapy. Long non-coding RNAs
(lncRNAs) are defined as transcripts of more than 200 nucleotides in length that
lack protein-coding potential. There is growing evidence that lncRNAs play an
important role in gene regulation, including oncogenesis. We present 13 lncRNA
genes involved in the pathogenesis of cutaneous melanoma through a variety of
pathways and molecular interactions. Some of these lncRNAs are possible
biomarkers or therapeutic targets for malignant melanoma.
PMID- 28415646
TI - Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11
translocation RCC: comparison of three different diagnostic methods.
AB - We evaluated the frequency of translocation renal cell carcinoma (RCC) by reverse
transcription polymerase chain reaction (RT-PCR) and how well the TFE3
immunoreactivity is concordant with TFE3 gene translocation status proved by
fluorescence in situ hybridization (FISH) assay and RT-PCR. TFE3 and Cathepsin K
expression was analyzed by immunohistochemistry in 185 RCC cases, and 48 cases
either of more than weak expression of TFE3 or of positivity for Cathepsin K were
done for FISH analysis and RT-PCR. All the RT-PCR positive cases were confirmed
by cloning and sequencing. Of the 14 cases with strong nuclear TFE3 expression,
12 showed a break-apart signal by FISH. ASPL- and PRCC-TFE3 translocations were
detected in 13 and one case, respectively, by RT-PCR. Of 21 cases with weak TFE3
expression, five were translocation-positive by FISH. ASPL-, PRCC-, and PSF-TFE3
translocations were detected by RT-PCR (n=3, 3, and 1, respectively). All 13 TFE3
negative/cathepsin K-positive cases were negative by FISH and two each harbored
ASPL- and PRCC-TFE3 translocations that were detected by RT-PCR. A high rate of
TFE3 immunoreactivity (8.6%) was confirmed by RT-PCR (13.5%) and FISH (9.7%).
Higher translocation rate of RT-PCR means RT-PCR detected translocation in TFE3
weak expression group and only cathepsin K positive group more specifically than
FISH. Thus, RT-PCR would complement FISH analysis for detecting translocation RCC
with fusion partners.
PMID- 28415645
TI - Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy.
AB - Peritoneal Carcinomatosis (PC) is a late stage manifestation of several
gastrointestinal malignancies including appendiceal, colorectal, and gastric
cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and
often leave patients with only palliative treatment options. For colorectal PC,
median survival is approximately five months, and palliative systemic therapy is
able to extend this to approximately 12 months. However, cytoreductive surgery
with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent
is possible in some patients with limited tumor burden. In well-selected patients
undergoing complete cytoreduction, median survival has been reported as high as
63 month. Identifying patients earlier who are either at risk for, or who have
recently developed PC may provide them with additional treatment options such as
CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an
invasive procedures such as laparoscopy or laparotomy. In order to improve the
outcomes of PC patients, a minimally invasive, accurate, and specific PC
screening method needs to be developed. By utilizing circulating PC biomarkers in
the serum of patients, a "liquid biopsy," may be able to be generated to allow a
tailored treatment plan and early intervention. Exosomes, stable patient-derived
nanovesicles present in blood, urine, and many other bodily fluids, show promise
as a tool for the evaluation of labile biomarkers. If liquid biopsies can be
perfected in PC, manifestations of this cancer may be more effectively treated,
thus offering improved survival.
PMID- 28415649
TI - An epigenetic master regulator teams up to become an epioncogene.
PMID- 28415647
TI - Contrast agents in dynamic contrast-enhanced magnetic resonance imaging.
AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive
method to assess angiogenesis, which is widely used in clinical applications
including diagnosis, monitoring therapy response and prognosis estimation in
cancer patients. Contrast agents play a crucial role in DCE-MRI and should be
carefully selected in order to improve accuracy in DCE-MRI examination. Over the
past decades, there was much progress in the development of optimal contrast
agents in DCE-MRI. In this review, we describe the recent research advances in
this field and discuss properties of contrast agents, as well as their advantages
and disadvantages. Finally, we discuss the research perspectives for improving
this promising imaging method.
PMID- 28415650
TI - A highly conserved redox-active Mx(2)CWx(6)R motif regulates Zap70 stability and
activity.
AB - zeta-associated protein of 70 kDa (Zap70) is crucial for T-cell receptor (TCR)
signaling. Loss of Zap70 in both humans and mice results in severe
immunodeficiency. On the other hand, the expression of Zap70 in B-cell
malignancies correlates with the severity of the disease. Because of its role in
immune-related disorders, Zap70 has become a therapeutic target for the treatment
of human diseases. It is well-established that the activity/expression of Zap70
is regulated by post-translational modifications of crucial amino acids including
the phosphorylation of tyrosines and the ubiquitination of lysines. Here, we have
investigated whether also oxidation of cysteine residues regulates Zap70
functions. We have identified C575 as a major sulfenylation site of Zap70. A
C575A substitution results in protein instability, reduced activity, and
increased dependency on the Hsp90/Cdc37 chaperone system. Indeed, Cdc37
overexpression reconstituted partially the expression but fully the function of
Zap70C575A. C575 lies within a Mx(2)CWx(6)R motif which is highly conserved among
almost all human tyrosine kinases. Mutation of any of the conserved amino acids,
but not of a non-conserved residue preceding the cysteine, also results in Zap70
instability. Collectively, we have identified a new redox-active motif which is
crucial for the regulation of Zap70 stability/activity. We believe that this
motif has the potential to become a novel target for the development of
therapeutic tools to modulate the expression/activity of kinases.
PMID- 28415651
TI - Diabetes mellitus and the risk of gastric cancer: a meta-analysis of cohort
studies.
AB - Studies examining the relationship between diabetes mellitus (DM) and the risk of
gastric cancer incidence or gastric cancer mortality have produced inconsistent
results. The purpose of this study was to evaluate the evidence regarding the
relationship between DM and subsequent gastric cancer incidence or gastric cancer
mortality risk on the basis of cohort studies. A systematic search of articles in
PubMed, EmBase, the Cochrane Library, and reference lists was conducted to
identify relevant literature. Twenty-two cohort studies reporting data on
8,559,861 participants were included in the study. Overall, participants with DM
had little or no change in the risk of gastric cancer, or gastric cancer
mortality. There was no evidence of difference in the RR for gastric cancer
between men and women. Participants with DM had a non-significant trend towards
an increased risk of gastric cancer mortality in men. There was no significant
difference between men and women for this relationship. Finally, although
subgroup analysis suggested DM was associated with a significant impact on
gastric cancer incidence and gastric cancer mortality risk in several specific
populations, a significance based on gender difference was not observed. In
conclusion, DM might increase the risk of gastric cancer in men when the study
used standard incidence/mortality ratio as effect estimate. Further, DM were
associated with higher risk of gastric cancer mortality in men if the mean age at
baseline less than 55.0 years, used RR or HR as effect estimate, the study
adjusted smoking or not, and the study not adjusted alcohol drinking.
PMID- 28415653
TI - Association between HIF1A rs11549465 polymorphism and risk of prostate cancer: a
meta-analysis.
AB - The hypoxia inducible factor 1-alpha (HIF1A) gene has been suggested to play a
critical role in cancer progression, and the relationship between HIF1A
rs11549465 polymorphism and risk of prostate cancer has been investigated in
previous studies. Nevertheless, conflicting results have been obtained. Hence, we
reevaluated this issue by means of this meta-analysis, with the purpose of
providing more precise conclusion on this issue. The electronic databases of
PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) as well as
other sources were searched for relevant reports concerning on the role of HIF1A
rs11549465 polymorphism in the occurrence of prostate cancer. The strength of the
relationship was determined by calculating odds ratios (ORs) with corresponding
95% confidence intervals (95% CIs). Besides, subgroup analyses by ethnicity and
source of control were further performed to examine this relationship. All
statistical analyses were performed using STATA software 12.0. Although HIF1A
rs11549465 polymorphism showed a tendency of increasing the risk of prostate
cancer, no statistical significance was detected under any genetic models.
Similar results were also revealed in subgroup analyses on the basis of ethnicity
and control source. Our findings indicate that HIF1A rs11549465 polymorphism may
not independently play a significant role in the occurrence of prostate cancer.
PMID- 28415654
TI - The associations between the MAPT polymorphisms and Alzheimer's disease risk: a
meta-analysis.
AB - Published studies revealed that the microtubule-associated protein tau (MAPT)
gene polymorphisms increased Alzheimer's disease (AD) risk; the associations of 4
single nucleotide polymorphisms (SNPs, rs242557G/A, rs2471738C/T, rs3785883G/A
and rs1467967A/G) of the MAPT gene with AD risk, however, remain inconclusive.
Here, we conducted a meta-analysis to investigate the relationship between the
MAPT SNPs and AD risk. A significant association of SNP rs242557 with AD risk was
found in a dominant [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.01,
1.10, P = 0.025] genetic model, and a suggestive association in an allelic (OR =
1.03, 95% CI = 1.00, 1.06, P = 0.078). When APOE epsilon 4 carrier status was
included in stratified analysis, this association was even stronger (allelic
model for the APOE epsilon 4 positive individuals: OR = 1.24, 95% CI = 1.08,
1.43, P = 0.003). Furthermore, a significant association of SNP rs2471738 with AD
risk was found under all the four models (allelic: OR = 1.11, 95% CI = 1.01,
1.20, P = 0.021; dominant: OR = 1.10, 95% CI = 1.00, 1.21, P = 0.046; recessive:
OR = 1.18, 95% CI = 1.05, 1.32, P = 0.004; additive: OR = 1.20, 95% CI = 1.07,
1.34, P = 0.002) models. However, pooled results suggest that the neither
rs3785883 nor rs1467967 is associated with AD risk under all the four genetic
models. In summary, our study provides further evidence of the associations of
the MAPT SNPs with AD risk.
PMID- 28415652
TI - The clinical role of microRNA-21 as a promising biomarker in the diagnosis and
prognosis of colorectal cancer: a systematic review and meta-analysis.
AB - This systematic analysis aimed to investigate the value of microRNA-21 (miR-21)
in colorectal cancer for multiple purposes, including diagnosis and prognosis, as
well as its predictive power in combination biomarkers. Fifty-seven eligible
studies were included in our meta-analysis, including 25 studies for diagnostic
meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta
analysis of miR-21 alone, the overall pooled results for sensitivity,
specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85
(0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented
corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89),
respectively. For the diagnostic meta-analysis of miR-21-related combination
biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87),
and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that
miRNA combination markers in circulation exhibited high predictive power, with
sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92
(0.89-0.94). For the prognostic meta-analysis, patients with higher expression of
miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio
(HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The
combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93),
respectively. Our comprehensive systematic review revealed that circulating miR
21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a
prognostic marker for colorectal cancer. In addition, miRNA combination
biomarkers may provide a new approach for clinical application.
PMID- 28415655
TI - Selective emodin toxicity in cancer cells.
PMID- 28415656
TI - Multivariate approaches to behavioral physiology.
PMID- 28415657
TI - ROS and radiotherapy: more we care.
PMID- 28415658
TI - Diagnostic and prognostic value of blood samples for KRAS mutation identification
in lung cancer: a meta-analysis.
AB - Circulating tumor DNA (ctDNA) and tumor cells (CTC) are novel approaches for
identifying genomic alterations. Thus, we designed a meta-analysis to evaluate
the diagnostic value and prognostic significance of a KRAS proto-oncogene, GTPase
(KRAS) mutation for lung cancer patients. All included articles were from PubMed,
EMBASE, Web of Science and Cochrane Library. Twelve articles that described 1,131
patients were reviewed. True positives (TP), false positives (FP), true negatives
(TN), and false negatives (FN) were used to calculate pooled sensitivity,
specificity, the positive likelihood ratio (PLR), the negative likelihood ratio
(NLR), a diagnostic odds ratio (DOR), the area under the curve (AUC) and
corresponding 95% confidence intervals (95% CI). PLR is calculated as
sensitivity/(1-specificity) and NLR is (1- sensitivity)/specificity. DOR is a
measured of diagnostic effectiveness (PLR/NLR). A survival analysis subgroup was
also designed to evaluate prognostic significance. Pooled sensitivity,
specificity, PLR, NLR, DOR and AUC were 0.79 (95% CI, 0.63-0.89), 0.93 (95% CI,
0.89-0.96), 12.13 (92% CI, 7.11-20.67), 0.22 (95% CI, 0.12-0.41), 54.82 (95% CI,
23.11-130.09), and 0.95 (95% CI, 0.93-0.96), respectively. KRAS mutation and wild
type hazard ratios for overall survival and progression-free survival were 1.37
(95% CI, 1.08-1.66), 1.46 (95% CI, 1.15-1.77) in blood samples, and 1.16 (95% CI,
1.03-1.28), 1.28 (95% CI, 1.09-1.46) in tumor tissue.
PMID- 28415659
TI - Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive
system: a meta-analysis.
AB - Several previous studies have reported the prognostic value of hexokinase 2 (HK2)
in digestive system tumors. However, these studies were limited by the small
sample sizes and the results were inconsistent among them. Therefore, we
conducted a meta-analysis based on 15 studies with 1932 patients to assess the
relationship between HK2 overexpression and overall survival (OS) of digestive
system malignancies. The relationship of HK2 and clinicopathological features was
also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence
intervals (CI) were calculated to estimate the effect size. Positive HK2
expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P < 0.001).
When stratified by tumor type, the impact of HK2 overexpression on poor prognosis
was observed in gastric cancer (HR = 1.77 [1.25-2.50], P < 0.001), hepatocellular
carcinoma (HR = 1.87 [1.58-2.21], P < 0.001), and colorectal cancer (HR = 2.89
[1.62-5.15], P < 0.001), but not in pancreatic ductal adencarcinoma (HR = 1.11
[0.58-2.11], P = 0.763). Furthermore, high HK2 expression was significantly
associated with some phenotypes of tumor aggressiveness, such as large tumor size
(OR = 2.03 [1.10-3.74], P = 0.024), positive lymph node metastasis (OR = 2.05
[1.39-3.02], P < 0.001), advanced clinical stage (OR = 2.17 [1.21-3.89], P =
0.009) and high alpha fetoprotein level (OR = 1.47 [1.09-2.02] P = 0.013). In
summary, HK2 might act as a prognostic indicator and a potential therapeutic
target of these digestive system cancers.
PMID- 28415660
TI - Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain
tissue.
AB - Raman spectroscopy could be applied to distinguish tumor from normal tissues.
This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in
differentiating brain tumor from normal brain tissue. PubMed and Embase were
searched to identify suitable studies prior to Jan 1st, 2016. We estimated the
pooled sensitivity, specificity, positive and negative likelihood ratios (LR),
diagnostic odds ratio (DOR), and constructed summary receiver operating
characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in
differentiating brain tumor from normal brain tissue. A total of six studies with
1951 spectra were included. For glioma, the pooled sensitivity and specificity of
Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99),
respectively. The area under the curve (AUC) was 0.9831. For meningioma, the
pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI
0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that
Raman spectroscopy could be an effective and accurate tool for differentiating
glioma and meningioma from normal brain tissue, which would help us both avoid
removal of normal tissue and minimize the volume of residual tumor.
PMID- 28415661
TI - Specific amplifications and copy number decreases during human neural stem cells
differentiation towards astrocytes, neurons and oligodendrocytes.
AB - There is growing evidence that gene amplifications are an attribute of normal
cells during development and differentiation. During neural progenitor cell
differentiation half of the genome is involved in amplification process. To
answer the question how specific amplifications occur at different stages and in
different lineages of differentiation we analyzed the genes CDK4, MDM2, EGFR,
GINS2, GFAP, TP53, DDB1 and MDM4 in human neural stem cells that were induced to
differentiate towards astrocytes, neurons and oligodendrocytes. We found specific
amplification pattern for each of the eight analyzed genes both in
undifferentiated neural stem and progenitor cells and in cells that were induced
for differentiation. Different amplification patterns were also found between
adherently grown neural stem cells and cells that were grown as spheres. The most
frequently amplified genes were MDM2 and CDK4 with the latter amplified in all
three lineages at all analyzed stages. Amplification of the analyzed genes was
also found in four glioma stem-like cells. The combined amplification data of
stem cells and of tumor stem cells can help to define cell populations at the
origin of the tumor. Furthermore, we detected a decrease of gene copies at
specific differentiation stages most frequently for MDM4. This study shows
specific amplification pattern in defined stem cell populations within specific
time windows during differentiation processes indicating that amplifications
occur in an orderly sequence during the differentiation of human neural stem and
progenitor cells.
PMID- 28415663
TI - Prognostic value of progesterone receptor expression in ovarian cancer: a meta
analysis.
AB - OBJECTIVE: While a prognosis value of progesterone receptor (PR) in ovarian
cancer has been reported in some publications, controversial data were presented
by different reports. In order to address the disagreement of progesterone
receptor in ovarian cancer survival, we conducted this meta-analysis. METHODS:
Relevant articles on progesterone receptor and ovarian cancer prognosis were
identified via a thorough search of PubMed, Embase and Cochrane Central. Hazard
ratios (HR) and 95% confidence interval (CI) were extracted from studies on
overall survival (OS) and disease-free survival (DFS)/progress-free survival
(PFS)/recurrence-free survival (RFS). RESULT: A total of 28 eligible studies
containing 5685 patients were collected for analysis. It was found that
progesterone receptor positivity was significantly associated with favorable
overall survival (OS) (HR = 0.86, 95% CI = 0.78 to 0.95, P = 0.002) and disease
free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS)
(HR = 0.75, 95% CI = 0.61 to 0.93, P = 0.008) of ovarian cancer patients.
Subgroup analysis showed that progesterone receptor expression was associated
with a favorable prognosis of unclassified ovarian cancer, European origin, and
immunohistochemical detection method. CONCLUSION: Progesterone receptor
expression can be used as a favorable prognostic predictor in ovarian cancer
managements.
PMID- 28415664
TI - Clinical application of the supraorbital key-hole approach to the treatment of
unilateral-dominant bilateral frontal contusions.
AB - We compared the surgical efficacy of the supraorbital key-hole approach (SKA) to
conventional unilateral frontotemporal craniotomy (UFTC) for the treatment of
patients with unilateral-dominant bilateral frontal contusions (BFCs). A
retrospective analysis of 62 patients with unilateral-dominant BFCs who underwent
surgery at our institute between 2014 and 2017 was performed. There were 26
patients who underwent SKA (group A) and 36 who underwent UFTC (group B).
Postoperative computed tomography scans showed satisfactory evacuation of the
frontal cerebral contusions in both groups (p > 0.05). There was less
intraoperative blood loss in group A than group B (17.1 +/- 4.55 vs. 67.6 +/-
10.28 mL, p < 0.05). The operative time was also shorter in group A (82.7 +/-
13.73 vs. 132.4 +/- 9.17 min, p < 0.05). Postoperative bleeding occurred in three
cases in group A and in only one case in group B (p > 0.05). The average length
of hospitalization was shorter in group A than group B (7.3 +/- 1.09 vs. 12.9 +/-
1.71 days, p < 0.05). No differences in the Glasgow Outcome Scale were observed
between the two groups after 6 months of follow-up (p > 0.05). Thus, compared to
UFTC, SKA is associated with shorter operation times and less trauma to the
surrounding brain tissue.
PMID- 28415662
TI - The hypoxia signalling pathway in haematological malignancies.
AB - Haematological malignancies are tumours that affect the haematopoietic and the
lymphatic systems. Despite the huge efforts to eradicate these tumours, the
percentage of patients suffering resistance to therapies and relapse still
remains significant. The tumour environment favours drug resistance of cancer
cells, and particularly of cancer stem/initiating cells. Hypoxia promotes
aggressiveness, metastatic spread and relapse in most of the solid tumours.
Furthermore, hypoxia is associated with worse prognosis and resistance to
conventional treatments through activation of the hypoxia-inducible factors.
Haematological malignancies are not considered solid tumours, and therefore, the
role of hypoxia in these diseases was initially presumed to be inconsequential.
However, hypoxia is a hallmark of the haematopoietic niche. Here, we will review
the current understanding of the role of both hypoxia and hypoxia-inducible
factors in different haematological tumours.
PMID- 28415667
TI - Effect of radiotherapy after breast-conserving surgery in older patients with
early breast cancer and breast ductal carcinoma in situ: a meta-analysis.
AB - BACKGROUND: There are no consistent agreements on whether radiotherapy after
breast-conserving surgery (BCS) could provide local control and survival benefit
for older patients with early breast cancer or breast ductal carcinoma in situ
(DCIS). The present study aimed to evaluate the efficacy of radiotherapy after
BCS in older patients with early breast cancer or DCIS. RESULTS: Radiotherapy
could reduce the risk of local relapse in older patients with early breast
cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non
radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25.
The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non
radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20.
However, radiotherapy could not improve survival benefits, including overall
survival, cancer-specific survival, breast-cancer-specific survival, and distant
relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast
events in older patients with DCIS. MATERIALS AND METHODS: PubMed and Embase
database were searched for relevant studies. Hazard ratios (HRs), risk ratios
(RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to
treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy
in older patients. CONCLUSIONS: Our study indicates that radiotherapy could
slightly reduce the risk of local relapse in older patients with favorable early
breast cancer. However, radiotherapy cannot translate into significant survival
benefits.
PMID- 28415668
TI - MiR-let-7a inhibits cell proliferation, migration, and invasion by down
regulating PKM2 in cervical cancer.
AB - In recent decades, miRNA has been reported as a crucial modulator in some biology
progressions. This work aims to assess the expression and role of miR-let-7a and
pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we
identified that miR-let-7a expression was decreased in CC tissues, and SiHa and
HeLa cells (all P < 0.001), however, PKM2 expression was increased in these
samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or
protein (p = 0.013, p = 0.015, respectively). In-vitro assays revealed that
ectopic miR-let-7a expression repressed SiHa and HeLa cell proliferation,
migration and invasion, and enhanced SiHa and HeLa cell apoptosis. Furthermore,
luciferase reporter assays revealed the 3'-UTR of PKM2 was identified a target of
miR-let-7a, by which miR-let-7a affected the expression of PKM2 in SiHa and HeLa
cells. Besides, PKM2 plasmids partially abrogated the inhibitory effects of miR
let-7a, while si-PKM2 enhanced the inhibitory effects of miR-let-7a. In vivo, miR
let-7a mimics indeed repressed tumor growth in mice xenograft model. In
conclusion, our results demonstrated that miR-let-7a inhibits cell proliferation,
migration and invasion by down-regulation of PKM2 in cervical cancer. miR-let
7a/PKM2 pathway may be a useful therapeutic target for CC patients.
PMID- 28415669
TI - Micro RNA-98 suppresses interleukin-10 in peripheral B cells in patient post
cardio transplantation.
AB - The immune tolerance to the transplant heart survival is critical. Regulatory B
cells are one of the major immune regulatory cell populations in the immune
tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as
the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis
that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10
expression in B cells (B10 cell) after heart transplantation. In this study, the
peripheral blood samples were collected from patients before and after heart
transplantation. The expression of miR-98 and IL-10 in B cells was assessed by
real time RT-PCR. An allograft heart transplantation mouse model was developed.
We observed that after heart transplantation, the frequency of peripheral B10
cell and the IL-10 mRNA levels in peripheral B cells were significantly
decreased, the levels of miR-98 were increased in peripheral B cells and the
serum levels of cortisol were increased in the patients. Treating naive B cells
with cortisol in the culture suppressed the expression of IL-10 in B cells, which
was abolished by knocking down the miR-98 gene. Administration with anti-miR-98,
or cortisol inhibitor, or adoptive transfer with B10 cells, significantly
enhanced the survival rate and time of mice received allograft heart
transplantation. In conclusion, the enhancement of serum cortisol affects the
immune tolerant feature of B cells, which can be attenuated by anti-miR-98
carrying liposomes.
PMID- 28415671
TI - Predictors and prognosticators for survival with Yttrium-90 radioembolization
therapy for unresectable colorectal cancer liver metastasis.
AB - This critical review aims to explore predictive and prognostic biomarkers of
Yttrium-90 (Y90) radioembolization therapy of colorectal liver metastases. A
brief overview of established predictive and prognostic molecular and genetic
biomarkers in colorectal cancer therapies will be discussed. A review of the
literature on imaging modalities, genetic, metabolic and other molecular markers
and the subsequent outcomes in post-Y90 treatment will be presented. How these
biomarkers and future biomarker research can inform locoregional treatment
decisions in the clinical setting of metastatic colorectal cancer lesions of the
liver will be explored. There are opportunities for personalized cancer treatment
in the setting of Y90 radioembolization. The ability to predict tumor response
after Ytrium-90 radioembolization therapy can greatly impact clinical decision
making and enhance treatment outcomes, therefore further research into the field
is needed.
PMID- 28415673
TI - cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2
induced learning/memory deficits of rats subjected to chronic unpredictable mild
stress.
AB - To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory
impairments in rats subjected to chronic unpredictable mild stress (CUMS),
meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2.
Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was
injected intraventricularly to increase or decrease the enzyme's expression,
respectively. The body weights and sucrose consumption were used to analyze
depressive behaviors, while the Morris water maze and step-down-type passive
avoidance tests were carried out to evaluate the learning-memory functions. The
levels of inflammatory cytokines were measured to estimate inflammation and the
contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels
of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed
using reverse transcription polymerase chain reaction. Moreover, the expression
of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins
receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein
(CREB), and phosphorylated CREB were estimated using immunohistochemical staining
or western blotting. The results showed that CUMS led to significant depressive
like behaviors and learning and memory dysfunctions. Also, the cAMP levels
decreased significantly, while levels of inflammatory cytokines and
prostaglandins E2 increased significantly. The expressions of PKA, BDNF,
phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam
and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS
while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities.
The findings also showed that CUMS increased cyclooxygenase 2 expression, which
can cause learning and memory impairments, mainly through activating the
hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.
PMID- 28415674
TI - Primary Sjogren's syndrome with diffuse cystic lung changes developed systemic
lupus erythematosus: a case report and literature review.
AB - Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease that can
occur as a unique existence (primary Sjogren's syndrome) or merge with other
systemic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis
or systemic sclerosis (secondary Sjogren's syndrome). Data on the two diseases
occurrence order are inadequate. Primary Sjogren's syndrome (pSS) may relatively
uncommonly lead to diffuse cystic lung changes. We represent a female who was
diagnosed pSS with diffuse cystic lung alterations developed SLE two years later.
SS was diagnosed on account of the existence of dryness of eye and mouth,
Schirmer's test, biopsy of the minor salivary glands of her lip, positive anti
SSA and anti-SSB antibody in the serum. Chest computed tomography image showed
bilateral diffuse cystic changes with a wide variation in cyst size and
distribution. SLE was finally diagnosed based on bilateral lower limb skin rash,
gonarthritis and omarthritis, low level of complement, antinuclear antibody 1:640
and positive antibodies to double-stranded DNA. Improvement was achieved with
therapy of corticosteroids, hydroxychloroquine and antibiotics. This report
provides us clinical, diagnosis and treatment perception of SS-onset SLE as
patient presenting diffuse cystic lung changes.
PMID- 28415675
TI - Elevated microRNA-135a is associated with pulmonary arterial hypertension in
experimental mouse model.
AB - Multiple causes are associated with the complex mechanism of pathogenesis of
pulmonary arterial hypertension (PAH), but the molecular pathway in the
pathogenesis of PAH is still insufficiently understood. In this study, we
investigated epigenetic changes that cause PAH induced by exposure to combined
Th2 antigen (Ovalbumin, OVA) and urban particulate matter (PM) in mice. To
address that, we focused on the epigenetic mechanism, linked to microRNA (miR)
135a. We found that miR-135a levels were significantly increased, and levels of
bone morphogenetic protein receptor type II (BMPR2) which is the target of miR
135a, were significantly decreased in this experimental PAH mouse model.
Therefore to evaluate the role of miR-135a, we injected AntagomiR-135a into this
mouse model. AntagomiR-135a injected mice showed decreased right ventricular
systolic pressures (RVSPs), right ventricular hypertrophy (RVH), and the
percentage of severely thickened pulmonary arteries compared to control scrambled
miRNA injected mice. Both mRNA and protein expression of BMPR2 were recovered in
the AntagomiR-135a injected mice compared to control mice. Our study understands
if miR-135a could serve as a biomarker helping to manage PAH. The blocking of miR
135a could lead to new therapeutic modalities to alleviate exacerbation of PAH
caused by exposure to Th2 antigen and urban air pollution.
PMID- 28415676
TI - Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge
of hippocampal neurons from epileptic rats.
AB - Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative
nucleoside transporter, could regulate the extracellular adenosine concentration
and have protective roles in seizures. However, the protection mechanism of NBTI
in seizures remains poorly understood. Here, the expression pattern and
subcellular distribution of adenosine A1 receptor were detected by Western blot
analysis and double-labeling immunofluorescence staining in Lithium Chloride
Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat
seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic
currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was
recorded using whole-cell patch clamp. In vivo, compared to control group,
Western blotting analysis showed that the expression of adenosine A1 receptor
protein was increased at 24 h and 72 h after seizure, didn't change at 0 min and
1 w, and decreased at 2 w. Double-label immunofluorescence revealed that
adenosine A1 receptor was mainly expressed in the membrane and cytoplasm of
neurons. In Vitro, adenosine decreased the eEPSCs amplitude of pyramidal neurons
in hippocampus CA1 region, NBTI also had the same effect. Meantime, NBTI could
further inhibit eEPSCs amplitude on the basis of lower concentration adenosine
(50uM), and adenosine A1 receptor inhibitor DPCPX partially reversed this effect.
Taken together, we confirmed that the expression of adenosine A1 receptor protein
was increased in the early seizures and decreased in the late seizures. At the
same time, NBTI mimics adenosine to attenuate the epileptiform discharge through
adenosine A1 receptor, which might provide a novel therapeutic approach toward
the control of epilepsy.
PMID- 28415677
TI - Selective elimination of long INterspersed element-1 expressing tumour cells by
targeted expression of the HSV-TK suicide gene.
AB - In gene therapy, effective and selective suicide gene expression is crucial. We
exploited the endogenous Long INterspersed Element-1 (L1) machinery often
reactivated in human cancers to integrate the Herpes Simplex Virus Thymidine
Kinase (HSV-TK) suicide gene selectively into the genome of cancer cells. We
developed a plasmid-based system directing HSV-TK expression only when reverse
transcribed and integrated in the host genome via the endogenous L1 ORF1/2
proteins and an Alu element. Delivery of these new constructs into cells followed
by Ganciclovir (GCV) treatment selectively induced mortality of L1 ORF1/2 protein
expressing cancer cells, but had no effect on primary cells that do not express
L1 ORF1/2. This novel strategy for selective targeting of tumour cells provides
high tolerability as the HSV-TK gene cannot be expressed without reverse
transcription and integration, and high selectivity as these processes take place
only in cancer cells expressing high levels of functional L1 ORF1/2.
PMID- 28415679
TI - A feasibility study of returning clinically actionable somatic genomic
alterations identified in a research laboratory.
AB - PURPOSE: Molecular profiling performed in the research setting usually does not
benefit the patients that donate their tissues. Through a prospective protocol,
we sought to determine the feasibility and utility of performing broad genomic
testing in the research laboratory for discovery, and the utility of giving
treating physicians access to research data, with the option of validating
actionable alterations in the CLIA environment. EXPERIMENTAL DESIGN: 1200
patients with advanced cancer underwent characterization of their tumors with
high depth hybrid capture sequencing of 201 genes in the research setting. Tumors
were also tested in the CLIA laboratory, with a standardized hotspot mutation
analysis on an 11, 46 or 50 gene platform. RESULTS: 527 patients (44%) had at
least one likely somatic mutation detected in an actionable gene using hotspot
testing. With the 201 gene panel, 945 patients (79%) had at least one alteration
in a potentially actionable gene that was undetected with the more limited CLIA
panel testing. Sixty-four genomic alterations identified on the research panel
were subsequently tested using an orthogonal CLIA assay. Of 16 mutations tested
in the CLIA environment, 12 (75%) were confirmed. Twenty-five (52%) of 48 copy
number alterations were confirmed. Nine (26.5%) of 34 patients with confirmed
results received genotype-matched therapy. Seven of these patients were enrolled
onto genotype-matched targeted therapy trials. CONCLUSION: Expanded cancer gene
sequencing identifies more actionable genomic alterations. The option of CLIA
validating research results can provide alternative targets for personalized
cancer therapy.
PMID- 28415680
TI - Long-term neurocognitive dysfunction in offspring via NGF/ ERK/CREB signaling
pathway caused by ketamine exposure during the second trimester of pregnancy in
rats.
AB - Early life exposure to ketamine caused neurohistopathologic changes and
persistent cognitive dysfunction. For this study, a pregnant rat model was
developed to investigate neurocognitive effects in the offspring, following
ketamine exposure during the second trimester. Pregnant rats on gestational day
14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg
ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition
test, and fear conditioning) at postnatal days (P25-30). Furthermore, hippocampal
morphology of the offspring (P30) was examined via Nissl staining and hippocampal
dendritic spine density was determined via Golgi staining. The hippocampal
protein levels of nerve growth factor (NGF), extracellular signal-regulated
kinase (ERK), phosphorylated-ERK (p-ERK), cyclic adenosine monophosphate response
element-binding (CREB), p-CREB, synaptophysin (SYP), synapsin (SYN), and
postsynaptic density-95 (PSD95) were measured via western blot. Additionally,
SCH772984 (an ERK inhibitor) was used to evaluate both role and underlying
mechanism of the ERK pathway in PC12 cells. We found that ketamine caused long
term neurocognitive dysfunction, reduced the density of the dendritic spin,
caused neuronal loss, and down-regulated the expression of NGF, ERK, p-ERK,
mitogen, and stress-activated protein kinase (MSK), CREB, p-CREB, SYP, SYN, and
PSD95 in the hippocampus. These results suggest that ketamine induced maternal
anesthesia during period of the fetal brain development can cause long-term
neurocognitive dysfunction in the offspring, which likely happens via inhibition
of the NGF-ERK-CREB pathway in the hippocampus. Our results highlight the central
role of ERK in neurocognition.
PMID- 28415681
TI - A reproducible model of intramedullary spinal cord tumor in rats bearing RG2
cells.
AB - Intramedullary spinal cord tumors (IMSCTs) are lethal diseases to many patients.
The lack of adequate animal model has hampered the development of novel
treatments. In the current study, a rodent intramedullary glioma model is
established to study IMSCT progression. Fischer 344 rats received a
intramedullary implantation of RG2 glioma cells. The neurological state of each
rat was evaluated on daily basis using the Basso, Beattie and Bresnahan (BBB)
scale. Rats implanted with RG2 cells developed significant hind limb paraplegia
20 days after implantation. Magnetic resonance imaging (MRI) scans after three
weeks revealed significant intramedullary RG2 tumors in the rats. Forty days post
implantation, rats were sacrificed for histopathological examination. Neuro
imaging and HE staining cross sections confirmed intramedullary RG2 glioma cells
invading to the spinal cord. Thus, our model displayed many of the same invasive
characteristics as human IMSCTs. This model should be a reliable and reproducible
methodology to correlate well with the features of human IMSCT.
PMID- 28415682
TI - Low dose of 2-deoxy-D-glucose kills acute lymphoblastic leukemia cells and
reverses glucocorticoid resistance via N-linked glycosylation inhibition under
normoxia.
AB - Recent studies showed that 2-deoxy-D-glucose (2-DG), a glucose analog with dual
activity of inhibiting glycolysis and N-linked glycosylation, can be selectively
taken up by cancer cells and be used as a potential chemo- and radio-sensitizer.
Meanwhile, 2-DG can kill cancer cells under normoxia. However, its efficacy is
limited by the high-dose induced systemic toxicity. Here, we showed that low-dose
2-DG could be used as a single agent to kill acute lymphoblastic leukemia (ALL)
cells, and as a GC sensitizer to overcome GC resistance under normoxia. Addition
of exogenous mannose, a sugar essential for N-linked glycosylation, rescued 2-DG
treated ALL cells, indicating that inhibition of N-linked glycosylation and
induction of endoplasmic reticulum stress is the main mechanism for 2-DG to
induce cell death and reverse GC resistance in ALL cells. These data provides new
insight into the molecular mechanisms involved in GC resistance. More important,
it indicates that 2-DG might be the promising drug for designing novel high
efficiency and low toxic protocol for ALL patients.
PMID- 28415683
TI - Suppression of PKC causes oncogenic stress for triggering apoptosis in cancer
cells.
AB - Gain of functional mutations in ras occurs in more than 30% of human malignancies
and in particular 90% of pancreatic cancer. Mutant ras, via activating multiple
effector pathways, not only promote cell growth or survival, but also apoptosis,
depending upon cell types or circumstances. In order to further study the
mechanisms of apoptosis induced by oncogenic ras, we employed the ras loop mutant
genes and demonstrated that Akt functioned downstream of Ras in human pancreatic
cancer or HPNE cells ectopically expressing mutated K-ras for the induction of
apoptosis after the concurrent suppression of PKC alpha and beta. In this
apoptotic process, the redox machinery was aberrantly switched on in the
pancreatic cancer cells as well as prostate cancer DU145 cells. p73 was
phosphorylated and translocated to the nucleus, accompanied with UPR activation
and induction of apoptosis. The in vitro results were corroborated by the in vivo
data. Thus, our study indicated that PKC alpha and beta appeared coping with
oncogenic Ras or mutated Akt to maintain the balance of the homeostasis in cancer
cells. Once these PKC isoforms were suppressed, the redox state in the cancer
cells was disrupted, which elicited persistent oncogenic stress and subsequent
apoptotic crisis.
PMID- 28415684
TI - The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma
driver genes by microRNA sponge activity.
AB - Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease
related gene expression, particularly in the central nervous system. Dysregulated
lncRNA expression has been documented in several human cancers, and their tissue
specificity makes them attractive candidates as diagnostic/prognostic biomarkers
and/or therapeutic agents. Here we show that linc-NeD125, which we previously
characterized as a neuronal-induced lncRNA, is significantly overexpressed in
Group 4 medulloblastomas (G4 MBs), the largest and least well characterized
molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA
induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p,
miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing
endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de
repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver
genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell
proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic
expression in the aggressive Group 3 MB cells attenuates their proliferation,
migration and invasion.This study unveils the first lncRNA-based ceRNA network in
central nervous system tumours and provides a novel molecular circuit underlying
the enigmatic Group 4 medulloblastoma.
PMID- 28415685
TI - Identification of molecular targets for esophageal carcinoma diagnosis using
miRNA-seq and RNA-seq data from The Cancer Genome Atlas: a study of 187 cases.
AB - Esophageal carcinoma (ESCA) is one of the most common malignancies worldwide, and
its pathogenesis is complex. In this study, we identified differentially
expressed miRNAs (DEMs) and genes (DEGs) of ESCA from The Cancer Genome Atlas
(TCGA) database. The diagnostic values of DEMs were determined by receiver
operating characteristic (ROC) analyses and validated based on data from Gene
Expression Omnibus (GEO). The top five DEMs with the best diagnostic values were
selected, and their potential targets were predicted by various in silico
methods. These target genes were then identified among the DEGs from TCGA.
Furthermore, the overlapping genes were subjected to protein-protein interaction
(PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
(KEGG) pathway analyses. The miRNA-transcription factor (TF) regulatory relations
were determined using CircuitsDB and TransmiR. Finally, the regulatory networks
of miRNA-TF and miRNA-gene were constructed and analyzed. A total of 136 DEMs and
3541 DEGs were identified in ESCA. The top five DEMs with the highest area under
the receiver operating characteristic curve (AUC) values were miRNA-93 (0.953),
miRNA-21 (0.928), miRNA-4746 (0.915), miRNA-196a-1 (0.906) and miRNA-196a-2
(0.906). The combined AUC of these five DEMs was 0.985. The KEGG analysis with
349 overlapping genes showed that the calcium signaling pathway and the
neuroactive ligand-receptor interaction were the most relevant pathways. The
regulatory networks of miRNA-TF and miRNA-gene, including 38 miRNA-TF and 560
miRNA-gene pairs, were successfully established. Our findings may provide new
insights into the molecular mechanisms of ESCA pathogenesis. Future research will
aim to explore the role of novel miRNAs in the pathogenesis and improve the early
diagnosis of ESCA.
PMID- 28415686
TI - Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose
tissue of mice through inhibition of NLRP3 inflammasome activation and NF-kappaB
signaling.
AB - Chronic metabolic inflammation in adipose tissue plays an important role in the
development of obesity-associated diseases. Our previous study indicated that
total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one
main component of SPJ, could exert the anti-oxidative and anti-inflammatory
effects. The present study aimed to investigate the in vivo and Ex vivo anti
inflammatory activities of another main component of SPJ, namely Chikusetsu
saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis,
and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA
expression levels of inflammation-related genes and secretion of the
chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages
(ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced
expression of NLRP3 inflammasome component genes and decreased IL-1beta and
Caspase-1 production in mice. Moreover, CS treatment also inhibited the
activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs).
Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and
lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed
HFD-induced NF-kappaB signaling in vivo and LPS-induced NF-kappaB activation as
reflected by the fact that their phosphorylated forms and the ratios of pNF
kappaB/NF-kappaB, pIKK/IKK, and pIkappaB/IkappaB were all decreased in EAT from
HFD-fed mice treated with CS as compared with those of HFD mice. Taking together,
this study has revealed that CS effectively inhibits HFD-induced inflammation in
adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and
NF-kappaB signaling. Thus, CS can serve as a potential therapeutic drug in the
prevention and treatment of inflammation-associated diseases.
PMID- 28415687
TI - The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small
cell lung cancer patients treated with definitive concurrent chemo-radiotherapy.
AB - BACKGROUND: This study aimed to investigate the prognostic impact of
supraclavicular lymph node (SCN) metastasis in patients who were treated with
definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer
(NSCLC). RESULTS: The 2- and 5-year overall survival (OS) rates were 57.3% and
35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN
metastasis, respectively. The median OS was 34 months in both groups. There was
no significant difference in OS between the two groups (p = 0.679). The 2- and 5
year progression-free survival (PFS) rates were 24.1% and 12.6% in patients
without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis,
respectively. Patients without SCN metastasis had slightly longer median PFS (10
months vs. 8 months), but the difference was not statistically significant (p =
0.223). In multivariate analysis, SCN metastasis was not a significant factor for
OS (p = 0.391) and PFS (p = 0.149). MATERIALS AND METHODS: This retrospective
analysis included 204 consecutive patients who were treated with
chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A
median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients
(58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease:
mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one
(1.2%). The patients were divided into two groups according to SCN metastasis.
CONCLUSIONS: SCN metastasis does not compromise treatment outcomes compared to
other mediastinal metastasis in the setting of definitive chemoradiotherapy.
PMID- 28415688
TI - Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3
M cells by competitively binding to oncogenic FABP5.
AB - Castration resistant-prostate cancer is largely impervious to feather hormonal
therapy and hence the outlook for patients is grim. Here we use an approach to
attach the recently discovered Achilles heel. The experimental treatment
established in this study is based on the recent discovery that it is the FABP5
PPARgamma-VEGF signalling axis, rather than the androgen receptor pathway, played
a dominant role in promoting the malignant progression of castration resistant
prostate cancer cells. Treatments have been established in mice by suppressing
the biological activity of FABP5 using a chemical inhibitor SBFI26. The inhibitor
significantly suppressed the proliferation, migration, invasiveness and colony
formation of PC3-M cells in vitro. It also produced a highly significant
suppression of both the metastases and the primary tumours developed from cancer
cells implanted orthotopically into the prostate glands of the mice. The
inhibitor SBFI26 interferes with the FABP5-PPARgamma- signalling pathway at the
initial stage of the signal transduction by binding competitively to FABP5 to
inhibit cellular fatty acid uptake. This avoids the fatty-acid stimulation of
PPARgamma and prevents it activating the down-stream regulated cancer-promoting
genes. This entirely novel experimental approach to treating castration-
resistant prostate cancer is completely different from current treatments that
are based on androgen-blockade therapy.
PMID- 28415689
TI - Targeting CD157 in AML using a novel, Fc-engineered antibody construct.
AB - Antibody-based immunotherapy represents a promising strategy to eliminate
chemorefractory leukemic cells in acute myeloid leukemia (AML). In this study, we
evaluated a novel Fc-engineered antibody against CD157 (MEN1112) for its
suitability as immunotherapy in AML. CD157 was expressed in 97% of primary AML
patient samples. A significant, albeit lower expression level of CD157 was
observed within the compartment of leukemia-initiating cells, which are supposed
to be the major source of relapse. In healthy donor bone marrow, CD157 was
expressed on CD34+ cells. In ex vivo assays, MEN1112 triggered natural killer
(NK) cell-mediated cytotoxicity against AML cell lines and primary AML cells.
Compared to its parental analogue, the Fc-engineered antibody exhibited higher
antibody dependent cellular cytotoxicity responses. Using NK cells from AML
patients, we observed heterogeneous MEN1112-mediated cytotoxicity against AML
cells, most likely due to well-documented defects in AML-NK cells and
corresponding inter-patient variations in NK cell function. Cytotoxicity could
not be correlated to the time after completion of chemotherapy. In summary, we
could demonstrate that CD157 is strongly expressed in AML. MEN1112 is a promising
antibody construct that showed high cytotoxicity against AML cells and warrants
further clinical testing. Due to variability in NK-cell function of AML patients,
the time of application during the course of the disease as well as combinatorial
strategies might influence treatment results.
PMID- 28415690
TI - Identification of DNA-PKcs as a primary resistance factor of TIC10 in
hepatocellular carcinoma cells.
AB - The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of
TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis
inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro
apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt
Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and
death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a
major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear
translocation. DNA-PKcs inhibition, knockdown or mutation facilitated TIC10
induced Foxo3a nuclear translocation, TRAIL/DR5 expression and cell apoptosis.
Reversely, exogenous DNA-PKcs over-expression inhibited above actions by TIC10.
In vivo, oral administration of TIC10 significantly inhibited HepG2 tumor growth
in nude mice, which was further potentiated with Nu7026 co-administration. Thus,
TIC10 shows promising anti-HCC activity, alone or together with DNA-PKcs
inhibitors.
PMID- 28415691
TI - A potentially functional variant of ARID1B interacts with physical activity in
association with risk of hepatocellular carcinoma.
AB - The tumor suppressor role of AT-rich interactive domain containing protein 1B
(ARID1B) has drawn much attention in area of cancer etiology. However, it had
remained unknown whether or not genetic variants of ARID1B involved in
development of hepatocellular carcinoma (HCC). In this study, three putatively
functional variants in ARID1B (rs73013281C>T, rs167007A>G, and rs9397984C>T) were
selected using bioinformatics tools, and a case-control study of 611 cases and
614 controls was conducted to investigate genetic associations with HCC risk in a
Southern Chinese population. Two-dimensional gene-environment interactions were
also explored using both multiplicative and additive scales. A dominant effect of
the rs73013281 was found for HCC risk, with an adjusted odds ratio (OR) of 1.70
[95% confidence interval (CI) = 1.03-2.80] for the CT/TT genotypes compared to
the CC genotype. In stratified analysis, the detrimental effect of the T allele
on elevated HCC risk was attenuated by physical activity, with an adjusted OR of
2.75 (95% CI = 1.39-5.41) among inactive individuals against that of 0.89 (95% CI
= 0.42-1.91) in those who exercised regularly. Expectably, the rs73013281 showed
both multiplicative and additive interactions with physical activity (P = 0.037
and 0.006, respectively). In conclusion, these results highlighted the
significant genetic contribution of the ARID1B variant, rs73013281, to
susceptibility for HCC, especially in interaction with physical activity.
PMID- 28415692
TI - Novel Akt activator SC-79 is a potential treatment for alcohol-induced
osteonecrosis of the femoral head.
AB - Alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH). We
explored the molecular mechanisms underlying alcohol-induced ONFH and
investigated the protective effect of the novel Akt activator SC-79 against this
disease. We found that ethanol inhibited expression of the osteogenic genes RUNX2
and OCN, downregulated osteogenic differentiation, impaired the recruitment of
Akt to the plasma membrane, and suppressed Akt phosphorylation at Ser473, thereby
inhibiting the Akt/GSK3beta/beta-catenin signaling pathway in bone mesenchymal
stem cells. To assess SC-79's ability to counteract the inhibitory effect of
ethanol on Akt-Ser73 phosphorylation, we performed micro-computerized tomography
and immunofluorescent staining of osteopontin, osteocalcin and collagen type 1 in
a rat model of alcohol-induced ONFH. We found that SC-79 injections inhibited
alcohol-induced osteonecrosis. These results show that alcohol-induced ONFH is
associated with suppression of p-Akt-Ser473 in the Akt/GSK3beta/beta-catenin
signaling pathway in bone mesenchymal stem cells. We propose that SC-79 treatment
to rescue Akt activation could be tested in the clinic as a potential therapeutic
approach to preventing the development of alcohol-induced ONFH.
PMID- 28415693
TI - CCR4 is a determinant of melanoma brain metastasis.
AB - We previously identified the chemokine receptor CCR4 as part of the molecular
signature of melanoma brain metastasis. The aim of this study was to determine
the functional significance of CCR4 in melanoma brain metastasis. We show that
CCR4 is more highly expressed by brain metastasizing melanoma cells than by local
cutaneous cells from the same melanoma. Moreover, we found that the expression of
CCR4 is significantly higher in paired clinical specimens of melanoma metastases
than in samples of primary tumors from the same patients. Notably, the expression
of the CCR4 ligands, Ccl22 and Ccl17 is upregulated at the earliest stages of
brain metastasis, and precedes the infiltration of melanoma cells to the brain.
In-vitro, CCL17 induced migration and transendothelial migration of melanoma
cells. Functionally, human melanoma cells over-expressing CCR4 were more
tumorigenic and produced a higher load of spontaneous brain micrometastasis than
control cells. Blocking CCR4 with a small molecule CCR4 antagonist in-vivo,
reduced the tumorigenicity and micrometastasis formation of melanoma cells. Taken
together, these findings implicate CCR4 as a driver of melanoma brain metastasis.
PMID- 28415694
TI - Single nucleotide polymorphisms in CIDEC gene are associated with metabolic
syndrome components risks and antihypertensive drug efficacy.
AB - The association of single nucleotide polymorphisms rs1053239 and rs2479 of cell
death-inducing DFFA-like effector c with the risk of metabolic syndrome and its
components, and with the efficacy and cost-effectiveness of antihypertensive
drugs was investigated. Totally 1064 subjects with metabolic syndrome and 1099
controls of Chinese Han nationality were recruited. Clinical assessment was
conducted with medication records collected at baseline and during 5-year follow
up. Carriers of rs2479 A allele were at higher risk to develop elevated fasting
glucose than non-carriers (P = 0.004). A allele at rs2479 were associated with a
5-year aggravation of blood triglyceride (P < 0.001) and diastolic blood pressure
(P = 0.003), and C allele at rs1053239 with the exacerbation of systolic (P <
0.001) and diastolic blood pressure (P = 0.001). Moreover, efficacy and cost
effectiveness of angiotensin II-targeted drugs were higher in subjects with
rs2479 A allele or rs1053239 C allele. These findings suggest that carriers of
rs2479 A allele are predisposed to the development of increased fasting glucose,
and the progressive elevation of blood triglyceride. Individuals with A allele at
rs2479 or C allele at rs1053239 are more susceptible to a rapid progression of
blood pressure, and benefit more from angiotensin II-targeted therapy.
PMID- 28415695
TI - Detection of COPB2 as a KRAS synthetic lethal partner through integration of
functional genomics screens.
AB - Mutated KRAS plays an important role in many cancers. Although targeting KRAS
directly is difficult, indirect inactivation via synthetic lethal partners (SLPs)
is promising. Yet to date, there are no SLPs from high-throughput RNAi screening,
which are supported by multiple screens. Here, we address this problem by
aggregating and ranking data over three independent high-throughput screens. We
integrate rankings by minimizing the displacement and by considering established
methods such as RIGER and RSA.Our meta analysis reveals COPB2 as a potential SLP
of KRAS with good support from all three screens. COPB2 is a coatomer subunit and
its knock down has already been linked to disabled autophagy and reduced tumor
growth. We confirm COPB2 as SLP in knock down experiments on pancreas and
colorectal cancer cell lines.Overall, consistent integration of high throughput
data can generate candidate synthetic lethal partners, which individual screens
do not uncover. Concretely, we reveal and confirm that COPB2 is a synthetic
lethal partner of KRAS and hence a promising cancer target. Ligands inhibiting
COPB2 may, therefore, be promising new cancer drugs.
PMID- 28415696
TI - Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta
analysis.
AB - Many molecular epidemiologic studies have explored the possible links between
interleukin-12 (IL-12) polymorphisms and various cancers. However, results from
these studies remain inconsistent. This meta-analysis is aimed to shed light on
the associations between three common loci (rs568408, rs2243115, rs3212227) of IL
12 gene and overall cancer risk. Our meta-analysis finally included 33 studies
comprising 10,587 cancer cases and 12,040 cancer-free controls. Odds ratios (ORs)
and 95% confidence intervals (CIs) were used to assess the cancer risk. We
observed a significant association between IL-12B rs3212227 and overall cancer
risk, especially in hepatocellular carcinoma, nasopharyngeal cancer, and among
Asians. IL-12A polymorphisms (rs2243115 and rs568408) were found no influence on
overall cancer risk. Nevertheless, stratification analyses demonstrated that
rs568408 polymorphism contributed to increasing cancer risk of Caucasians and
cervical cancer. And, rs2243115 may enhance the risk of brain tumor. These
findings provided evidence that IL-12 polymorphisms may play a potential role in
cancer risk.
PMID- 28415697
TI - Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous
system demyelination.
AB - Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of
multiple sclerosis (MS), though the mechanisms are not clear. Because myelin
expression is highly conserved between zebrafish and mammals, zebrafish have
become an ideal model for studying demyelination. We used a transgenic (Tg;
mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green
fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult
transgenic zebrafish to metronidazole induced demyelination that resembled the
morphological changes associated with the early stages of MS. The metronidazole
induced demyelination was confirmed by magnetic resonance imaging (MRI) for the
first time. Microarray analysis revealed down-regulation of IL-7R during
demyelination. Targeted knockdown of IL-7R demonstrated that IL-7R is essential
for myelination in embryonic and larval zebrafish. Moreover, IL-7R down
regulation induced signaling via the JAK/STAT pathway leading to apoptosis in
oligodendrocytes. These findings contribute to our understanding of the role of
IL-7R in demyelination, and provide a rationale for the development of IL-7R
based therapies for MS and other demyelinating diseases.
PMID- 28415698
TI - Salivary glycopatterns as potential biomarkers for diagnosis of gastric cancer.
AB - Gastric cancer (GC) is still an extremely severe health issue with high mortality
due to the lacking of effective biomarkers. In this study, we aimed to
investigate the alterations of salivary protein glycosylation related to GC and
assess the possibility of salivary glycopatterns as potential biomarkers for the
diagnosis of GC. Firstly, 94 patients with GC (n = 64) and atrophic gastritis
(AG) (n = 30), as well as 30 age- and sex-matched healthy volunteers (HV) were
enrolled in the test group to probe the difference of salivary glycopatterns
using lectin microarrays, the results were validated by saliva microarrays and
lectin blotting analysis. Then, the diagnostic model of GC (Model GC) and AG
(Model AG) were constructed based on 15 candidate lectins which exhibited
significant alterations of salivary glycopattern by logistic stepwise regression.
Finally, two diagnostic models were assessed in the validation group including HV
(n = 30) and patients with GC (n = 23) and AG (n = 24) and achieved high
diagnostic power (Model GC (AUC: 0.89, sensitivity: 0.96 and specificity: 0.80),
Model AG (AUC: 0.83, sensitivity: 0.92 and specificity: 0.72)). This study
provides pivotal information to distinguish HV, AG and GC based on precise
alterations in salivary glycopatterns, which have great potential to be
biomarkers for diagnosis of GC.
PMID- 28415699
TI - The prognostic value of histological subtype in patients with metastatic bladder
cancer.
AB - We aim to evaluate the prognostic effect of the histological sub-type in patients
with metastatic bladder cancer based on the Surveillance Epidemiology and End
Results database. A total of 2634 eligible patients were included. The
histological subtypes were: transitional cell carcinoma (TCC; 75.2%);
adenocarcinoma (3.3%); squamous cell carcinoma (SQCC; 4.1%); and small cell
carcinoma (4.3%). A significant association of adenocarcinoma with better
survival outcomes (P < 0.015), and that of SQCC with worse outcomes (P < 0.001)
was observed. On multivariate analysis, adenocarcinoma was significantly
associated with longer and SQCC with shorter survival time as compared to TCC.
Overall, 1331 (50.5%) patients had a single metastatic site and 523 (19.9%) had
multiple sites involved. Single-site metastasis had a better survival outcome
than multiple metastases (P < 0.001). Histological sub-type and presence of
multiple metastatic sites are independent predictors of survival time.
Prospective, in-depth research is needed to determine optimal therapeutic
strategies for different histological subtypes of bladder cancer with different
metastatic patterns.
PMID- 28415700
TI - Circulating tumor cells promote the metastatic colonization of disseminated
carcinoma cells by inducing systemic inflammation.
AB - Circulating tumor cells (CTCs) have been studied well in the prognosis for
malignant diseases as liquid biopsy, but their contribution to tumor metastasis
is not clearly defined. Here we report that CTCs could promote the metastatic
colonization of disseminated carcinoma cells by inducing systemic inflammation
and neutrophil recruitment to pre-metastatic organs. Depletion of neutrophils in
vivo could effectively abrogate the promoting effect of CTCs on tumor cell
metastasis. In the presence of CTCs, the pro-tumor function of neutrophils was
augmented, whereas the antitumor function of neutrophils was suppressed.
Mechanically, CTC-derived ligands for TLR2 and TLR4 (TLR2/4) induced the systemic
inflammation, thus increasing the production of proinflammatory cytokines such as
G-CSF and IL-6 that could induce the conversion of neutrophil function from tumor
suppressing to tumor-promoting. Moreover, CTCs induced the production of
endogenous TLR2/4 ligands such as S100A8, S100A9, and SAA3, which may amplify the
stimulating effect that induces the expression of proinflammatory cytokines. The
promoting effect of CTCs on tumor cell metastasis could be abrogated by
suppressing inflammatory response with IL-37, an anti-inflammatory cytokine, or
blocking CTC-derived ligands for TLR2/4. Identification of the metastatic axis of
CTCs/systemic inflammation/neutrophils may provide potential targets for
preventing tumor cell metastasis.
PMID- 28415701
TI - Wogonin induces retinal neuron-like differentiation of bone marrow stem cells by
inhibiting Notch-1 signaling.
AB - Age-related macular degeneration and retinitis pigmentosa are major causes of
irreversible vision loss in the elderly and, despite sustained efforts, current
treatments are largely ineffective. Wogonin is a bioactive plant flavonoid
possessing a range of beneficial properties, including neuroprotective effects.
We investigated the ability of wogonin to promote retinal neuron-like
differentiation of bone marrow stem cells (BMSCs) and assessed the involvement of
Notch-1 signaling in this process. Cultured mouse BMSCs were left untreated or
exposed to neurotrophic factors in the presence or absence of wogonin, and
western blotting, RT-PCR and immunofluorescence were used to identify changes in
molecular markers of stemness and neuroretinal differentiation. Proteins in the
Notch-1 signaling pathway, a main negative regulator of neurogenesis, were also
examined by western blotting. We found that expression of stem cell markers was
reduced, while markers of mature retinal neurons, bipolar cells and
photoreceptors were increased in wogonin-treated BMSCs. Wogonin also dose
dependently decreased expression of Notch-1 signaling proteins. Moreover,
blockade of Notch-1 both mimicked and enhanced the effect of wogonin to
facilitate BMSC differentiation into retinal neuron-like cells. Wogonin thus
appears to promote retinal neuron-like differentiation of BMSCs by antagonizing
the inhibitory actions of Notch-1 signaling on neurogenesis and may be useful in
the treatment of retinal degenerative diseases.
PMID- 28415702
TI - Overexpression of CXCR2 predicts poor prognosis in patients with colorectal
cancer.
AB - Colorectal cancer is a heterogeneous disease. Although many risk factors are used
to predict colorectal cancer patients' prognosis after surgical resection, new
prognostic factors are still needed to be defined to promote predictive efficacy
of prognosis and further guide therapies. Herein, we identified the prognostic
significance of CXCR2 in colorectal cancer patients. We retrospectively analysed
134 patients with colorectal cancer who underwent minimally invasive surgery
between 2010 and 2011. The overall cohort was divided into a training set (n =
78) and a validation set (n = 56). We detected CXCR2 expression using
immunohistochemical staining and defined the cut-off value using X-tile program.
Next, we analysed the association between CXCR2 expression and clinicopathologic
features in training and validation sets. High expression of CXCR2 was associated
with Dukes stage (P = 0.018), tumor invasion (P = 0.018) and liver metastasis (P
= 0.047). Multivariate COX regression analyses confirmed that high CXCR2 level
was an independent prognostic risk factor for both overall survival and disease
free survival. Kaplan-Meier survival analysis demonstrated that patients with
high expression of CXCR2 had a poor overall survival and disease free survival
even in low-risk group (I + II). This indicated that CXCR2 can help to refine
individual risk stratification. In addition, we established Nomograms of all
significant factors to predict 3- or 5-years overall survival and disease free
survival. Moreover, we found the combination of CXCR2 and its ligand CXCL5 had
more significant value in predicting the prognosis than single CXCR2 factor.
PMID- 28415703
TI - Bromodomain protein 4 is a novel predictor of survival for gastric carcinoma.
AB - Expression of bromodomain protein 4 (BRD4) has been reported to predict a worse
prognosis in solid tumors. However, its expression profile and prognostic value
in gastric carcinoma (GC) remains unknown. Here we investigated BRD4 expression
in GC and explored its association with patient survival. Tissue samples were
obtained from 95 GC patients who underwent surgical resection to remove the
primary tumor from January 2009 to December 2010. Immunohistochemistry was used
to detect the expression of BRD4 in GC tissues and adjacent normal tissues.
Kaplan-Meier survival curves and Cox proportional hazards regression were used to
analyze the data of BRD4 expression profile and clinicopathological
characteristics. Immunohistochemical analysis revealed BRD4 was overexpressed in
GC tissue compared with adjacent normal tissue. BRD4 expression was significantly
associated with TNM stage (p < 0.001), lymphatic permeation (p = 0.011), and
vital status at the end of follow-up (p < 0.001). Kaplan-Meier survival curves
and the log-rank test demonstrated that higher BRD4 expression was an adverse
predictive factor for survival in GC. Multivariate analysis by Cox proportional
hazards regression revealed that BRD4 expression was an independent worse
prognostic factor in GC. In conclusion, BRD4 could act as a potential biomarker
for prognostic assessment of GC.
PMID- 28415704
TI - Maternal exposure to di-n-butyl phthalate (DBP) induces renal fibrosis in adult
rat offspring.
AB - This study was to determine the impact of maternal exposure to di-n-butyl
phthalate (DBP) on renal development and fibrosis in adult offspring. Pregnant
rats received DBP at a dose of 850 mg/kg BW/day by oral perfusion during
gestational days 14-18. In DBP exposed newborn offspring, gross observation and
histopathological examination revealed the dysplasia of kidney. The expression of
genes related to renal development was also changed. In DBP exposed adult
offspring, histopathological examination and Masson's trichrome staining revealed
the pathological changes of renal fibrosis. Furthermore, higher expression levels
of transforming growth factor- beta (TGF-beta) and alpha-smooth muscle actin
(alpha-SMA) were also detected. In vitro studies reveal that DBP promoted the
activation of NRK49F cells and G2/M arrest in NRK52E cells at a sublethal dose.
The effect of DBP on these cell lines was linked to the generation of oxidative
stress. In addition, DBP induced oxidative stress in both renal fibroblasts and
tubular epithelial cells, whereas vitamin C ameliorated the changes caused by
DBP. In conclusion, our results showed that prenatal exposure to DBP may generate
oxidative stress in both renal fibroblasts and tubular epithelial cells, leading
to kidney dysplasia and renal fibrosis.
PMID- 28415705
TI - Meta-analysis of XRCC1 polymorphism and risk of female reproductive system
cancer.
AB - Numerous epidemiological studies have evaluated the association between
polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1)
protein and the risk of female reproductive system cancer, but results are
inconclusive. To gain a comprehensive picture of available evidence, we searched
for relevant studies in the PubMed, EMBASE, Scopus, and Chinese National
Knowledge Infrastructure databases up to December 17, 2016. A total of 26 case
control studies were picked out. The pooled odds ratio (OR) with its 95%
confidence interval (CI) was calculated to estimate the association. Based on
data of all study participants, we did not find a positive association of rs25487
or rs1799782 polymorphism with risk of female reproductive cancer risk. Subgroup
analysis, however, identified two alleles as being associated with an increased
risk of female reproductive system cancer in Asians: the A allele of rs25487
(heterozygous genetic model, OR 1.16, 95%CI 1.00-1.36), and the T allele of
rs1799782 (homozygous model, OR 2.30, 95%CI 1.39-3.82; dominant model, OR 1.28,
95%CI 1.10-1.50; recessive model, OR 2.11, 95%CI 1.33-3.34). Moreover, the AA
genotype at rs25489 was determined to be a risk factor for cervical cancer
etiology (homozygous model, OR 2.91, 95%CI, 1.17-7.26; recessive model, OR 3.16,
95%CI 1.91-5.24). This meta-analysis suggests that no association between rs25487
or rs1799782 gene polymorphism and risk of female reproductive cancer risk was
found. These results should be validated in larger studies.
PMID- 28415706
TI - The role of targeted agents in the adjuvant treatment of colon cancer: a meta
analysis of randomized phase III studies and review.
AB - There has been debate as to whether targeted agents have beneficial effect when
added to adjuvant chemotherapy for patient with colon cancer. We conducted this
meta-analysis to investigate the role of targeted agents in the adjuvant
treatment of colon cancer. We searched PubMed, MEDLINE, EMBASE, and the Cochrane
Library databases. We included phase III trials with the data of disease-free
survival (DFS) and adverse events (AEs) of adjuvant treatment with targeted
agents. From 5 eligible studies, a total of 9,991 patients with resected colon
cancer were included in the meta-analysis of hazard ratio (HR) for 3-year DFS and
odds ratio (OR) for grade 3 or higher AEs. The addition of targeted agents showed
no improvement of 3-year DFS, compared to standard adjuvant chemotherapy alone
(HR = 1.04 [95% confidence interval (CI), 0.96-1.13], P = 0.31). In the subgroup
analysis according to the type of targeted agents, neither bevacizumab (HR = 1.03
[95% CI, 0.88-1.21], P = 0.72) nor cetuximab (HR = 1.11 [95% CI, 0.94-1.31], P =
0.22) was associated with improvement of DFS. Moreover, targeted agents
significantly increased grade 3 or higher AEs (OR = 1.73 [95% CI, 1.21-2.46], P =
0.003) and treatment-related death (OR = 2.15 [95% CI, 1.16-3.99], P = 0.02). In
conclusion, this meta-analysis demonstrates that the addition of targeted agents
to standard adjuvant chemotherapy results in no improvement of DFS with increased
severe AEs and treatment-related death in patients with resected colon cancer.
PMID- 28415707
TI - Luteolin reduces inflammation in Staphylococcus aureus-induced mastitis by
inhibiting NF-kB activation and MMPs expression.
AB - Mastitis is a serious and prevalent disease caused by infection by pathogens such
as Staphylococcus aureus. We evaluated the anti-inflammatory effects and
mechanism of luteolin, a natural flavonoid with a wide range of pharmacological
activities, in a mouse model of S. aureus mastitis. We also treated cultured
mouse mammary epithelial cells (mMECs) with S. aureus and luteolin.
Histopathological changes were examined by H&E staining and the levels of
inflammatory cytokine proteins were analyzed using ELISAs. We determined mRNA
levels with qPCR and the level of NF-kappaB and matrix metalloproteinase (MMP)
proteins by Western blotting. The observed histopathological changes showed that
luteolin protected mammary glands with S. aureus infection from tissue
destruction and inflammatory cell infiltration. Luteolin inhibited the expression
of TNF-alpha, IL-1beta, and IL-6, all of which were increased with S. aureus
infection of mammary tissues and mMECs. S. aureus-induced TLR2 and TLR4 was
suppressed by luteolin, as were levels of IkappaBalpha and NF-kappaB p65
phosphorylation and expression of MMP-2 and MMP-9. Levels of tissue inhibitor of
metalloproteinases (TIMP)-1 and TIMP-2 were enhanced. These findings suggest
luteolin is a potentially effective new treatment to reduce tissue damage and
inflammation from S. aureus-induced mastitis.
PMID- 28415708
TI - Human papillomavirus subtypes distribution among 2309 cervical cancer patients in
West China.
AB - OBJECTIVE: The prevalence of cervical Human Papillomavirus (HPV) infection in
cervical cancer varies greatly worldwide, and HPV prevalence and genotypes in
China are limited. The objective is to analyze the prevalence of HPV subtypes in
cervical cancer patients in west China as well as the relationships between
different histological types of cervical cancer and HPV subtypes. RESULTS: 2309
cases were included. 90.86% were infected with HPV, and the remaining 9.13% were
negative. The most common subtypes were HPV16, HPV18, HPV58, HPV53, and HPV33.
HPV16 and HPV18 appeared to be the most prevalent HPV subtypes across all age
groups, while the prevalence of the other subtypes varied between age groups. A
logistic regression analysis revealed that the occurrence of cervical squamous
cell carcinoma and adenocarcinoma was most closely correlated to a persistent
infection with HPV16 or HPV18, with P < 0.05. MATERIALS AND METHODS: The
prevalence of 27 HPV subtypes in 2309 cervical cancer patients who received
treatment at our hospital between June 2011 and January 2016 was analyzed based
on the results of HPV testing using Liquid suspension chip technology (Luminex
200). CONCLUSIONS: HPV16 and HPV18 were the most prevalent HPV subtypes among the
cervical cancer patients, followed by HPV58, HPV53, and HPV33. 9.13% of the cases
appeared to not be associated with HPV. This suggests that HPV testing without
the use of cytology may overlook some special types of cervical cancer that
account for approximately 10% of all cervical cancer cases.
PMID- 28415709
TI - A peptide derived from apoptin inhibits glioma growth.
AB - Glioblastoma (GBM) is associated with poor prognosis due to its resistance to
surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic
approaches for the treatment of GBM are urgently needed. HSP70 is an
antiapoptotic protein that participates in the inhibition of both mitochondrial
and membrane receptor apoptosis pathways and is highly expressed in glioma
tissues. Here, we investigated a derivative of apoptin; specifically, a chicken
anemia viral protein with selective toxicity toward cancer cells that can inhibit
hyperactive molecules, including HSP70. Our earlier studies demonstrated that
apoptin directly binds to the promoter of HSP70 and inhibits HSP70 transcription,
which contributes to HSP70 downregulation. This study provides the first
demonstration of the therapeutic potential of an apoptin-derived peptide for the
treatment of GBM by identifying the minimal region of the apoptin domain required
for interaction with the heat-shock element (HSE). This apoptin-derived peptide
(ADP) inhibits glioma cell proliferation and tumor growth as well as exhibits an
increased ability to promote apoptosis in GBM cells compared with rapamycin and
temozolomide. ADP treatment inhibited xenograft tumor growth and increased the
overall health and survival of nude mice implanted with GBM cells. These effects
were measured in tumors obtained from cell lines and were observed in both
intracranial and subcutaneous xenografts. In conclusion, we provide the first
demonstration that ADP has therapeutic potential for the treatment of human GBM.
Specifically, this study suggests that ADP is a potent candidate for drug
development based on its favorable toxicity and pharmacokinetic profiles as well
as its time- and cost-saving benefits.
PMID- 28415710
TI - Marital status and survival of patients with oral cavity squamous cell carcinoma:
a population-based study.
AB - BACKGROUND: The relationship between marital status and oral cavity squamous cell
carcinoma (OCSCC) survival has not been explored. The objective of our study was
to evaluate the impact of marital status on OCSCC survival and investigate the
potential mechanisms. RESULTS: Married patients had better 5-year cancer-specific
survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs
41.1%). In multivariate Cox regression models, unmarried patients also showed
higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence
interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P
< 0.001). Multivariate logistic regression showed married patients were more
likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P <
0.001). Married patients still demonstrated better prognosis in the 1:1 matched
group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). MATERIALS AND METHODS:
11022 eligible OCSCC patients were identified from Surveillance, Epidemiology,
and End Results (SEER) database, including 5902 married and 5120 unmarried
individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards
regression model were used to analyze survival and mortality risk. Influence of
marital status on stage, age at diagnosis and selection of treatment was
determined by binomial and multinomial logistic regression. Propensity score
matching method was adopted to perform a 1:1 matched cohort. CONCLUSIONS:
Marriage has an independently protective effect on OCSCC survival. Earlier
diagnosis and more sufficient treatment are possible explanations. Besides, even
after 1:1 matching, survival advantage of married group still exists, indicating
that spousal support from other aspects may also play an important role.
PMID- 28415711
TI - Mutational analysis of multiple lung cancers: Discrimination between primary and
metastatic lung cancers by genomic profile.
AB - In cases of multiple lung cancers, individual tumors may represent either a
primary lung cancer or both primary and metastatic lung cancers. Treatment
selection varies depending on such features, and this discrimination is
critically important in predicting prognosis. The present study was undertaken to
determine the efficacy and validity of mutation analysis as a means of
determining whether multiple lung cancers are primary or metastatic in nature.
The study involved 12 patients who underwent surgery in our department for
multiple lung cancers between July 2014 and March 2016. Tumor cells were
collected from formalin-fixed paraffin-embedded tissues of the primary lesions by
using laser capture microdissection, and targeted sequencing of 53 lung cancer
related genes was performed. In surgically treated patients with multiple lung
cancers, the driver mutation profile differed among the individual tumors.
Meanwhile, in a case of a solitary lung tumor that appeared after surgery for
double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy
sample revealed a gene mutation profile consistent with the surgically resected
specimen, thus demonstrating that the tumor in this case was metastatic. In cases
of multiple lung cancers, the comparison of driver mutation profiles clarifies
the clonal origin of the tumors and enables discrimination between primary and
metastatic tumors.
PMID- 28415712
TI - Association analysis of telomere length related gene ACYP2 with the gastric
cancer risk in the northwest Chinese Han population.
AB - Gastric cancer (GC) is a complex multifactorial disease, and genetic factors are
believed the predominant cause to the occurrence of GC. We sought to investigate
the associations between single nucleotide polymorphisms (SNPs) in ACYP2 gene and
the risk of GC in the Northwest Chinese Han population. We recruited 302 GC cases
and 300 controls from northwest China and selected 13 SNPs from ACYP2 gene. SNPs
were genotyped using Sequenom Mass-ARRAY technology. Odds ratios (ORs) and 95 %
confidence intervals (CIs) were used to assess the association. Bonferroni's
multiple adjustment was applied to the level of significance, which was set at P
< 0.00078 (0.05/65). We found that the minor alleles of rs6713088, rs11125529,
rs12615793, rs843711, rs11896604, rs843706 and rs17045754 significantly
stimulated the risk of GC, and homozygous alleles of above SNPs except rs6713088
were also found increasing the GC risk (P < 0.05). Under additive model and
recessive model, rs11125529, rs12615793, rs843711, rs11896604, and rs17045754
also activated the risk of GC (P < 0.05). However, after Bonferroni's multiple
adjusted was applied to our data, no SNP in our study was significantly related
to GC risk. Further results of haplotype analysis founds that the haplotypes
"TTCTAATG" (rs1682111, rs843752, rs10439478, rs843645, rs11125529, rs12615793,
rs843711, and rs11896604) and "AC" (rs843706 and rs17045754) were more frequency
among patients with GC, on the contrary, the haplotypes "CG" had a protective
role in the GC risk (P < 0.05). Our results indicate that ACYP2 polymorphisms may
influence the GC risk and may serve as a new precursory biomarker in the
northwest Chinese Han population.
PMID- 28415713
TI - miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway.
AB - Tumor metastasis has been the major cause of recurrence and death in patients
with gastric cancer. Here, we find miR-135a has a decreased expression in the
metastatic cell lines compared with its parental cell lines by analyzing microRNA
array. Further results show that miR-135a is downregulated in the majority of
human gastric cancer tissues and cell lines. Decreased expression of miR-135a is
associated with TNM stage and poor survival. Besides, regaining miR-135a in
gastric cancer cells obviously inhibits tumor growth, migration, invasion and
angiogenesis by targeting focal adhesion kinase (FAK) pathway. Bioinformatics
analysis and molecular experiments further prove that miR-135a is a novel
downstream gene of tumor suppressor p53. Blocking FAK with its inhibitor can also
enhance miR-135a expression through inducing p53. In summary, this study reveals
the expression and function of miR-135a in gastric cancer and uncovers a novel
regulatory mechanism of miR-135a.
PMID- 28415714
TI - Depth of response is a significant predictor for long-term outcome in advanced
gastric cancer patients treated with trastuzumab.
AB - PURPOSE: We aimed to determine and compare the predictive values of depth of
response (DpR) and early tumor shrinkage (ETS) on long-term outcomes in gastric
cancer patients treated with trastuzumab. RESULTS: From a total of 368 computed
tomography examinations, DpR and ETS were evaluated. DpR was a significant tumor
size metric in predicting PFS and OS, and showed better discriminatory ability
(higher Ctau indices, 0.6957 for PFS; 0.7191 for OS) than ETS. DpR >= 45% (vs. <
45%) was the optimal cutoff value, as it was best able to identify patients with
longer PFS (median 9.0 vs. 6.3 months, hazard ratio [HR] = 0.608; 95% confidence
interval [CI]: 0.335 to 1.104; P = 0.102) and OS (median 23.5 vs. 13.1 months, HR
= 0.441; 95% CI: 0.203 to 0.955; P = 0.038). MATERIALS AND METHODS: Sixty-one
gastric cancer patients who received first-line trastuzumab-based chemotherapy
were assessed for DpR and ETS. We employed Kaplan-Meier estimates, log-rank
tests, Cox proportional hazards regression models, time-dependent receiver
operating characteristics, and Youden's J index to evaluate and determine cutoff
values of DpR and ETS as predictors of progression-free survival (PFS) and
overall survival (OS). CONCLUSIONS: DpR and ETS were significant predictors of
long-term outcomes in gastric cancer patients treated with first-line
trastuzumab. Validation in prospective trials with larger patient populations is
needed.
PMID- 28415715
TI - Epha3 acts as proangiogenic factor in multiple myeloma.
AB - This study investigates the role of ephrin receptor A3 (EphA3) in the
angiogenesis of Multiple Myeloma (MM) and the effects of a selective target of
EphA3 by a specific monoclonal antibody on primary bone marrow endothelial cells
(ECs) of MM patients.EphA3 mRNA and protein were evaluated in ECs of MM patients
(MMECs), in ECs of patients with monoclonal gammopathies of undetermined
significance (MGECs) and in ECs of healthy subjects (control ECs). The effects of
EphA3 targeting by mRNA silencing (siRNA) or by the anti EphA3 antibody on the
angiogenesis were evaluated. We found that EphA3 is highly expressed in MMECs
compared to the other EC types. Loss of function of EphA3 by siRNA significantly
inhibited the ability of MMECs to adhere to fibronectin, to migrate and to form
tube like structures in vitro, without affecting cell proliferation or viability.
In addition, gene expression profiling showed that knockdown of EphA3 down
modulated some molecules that regulate adhesion, migration and invasion
processes. Interestingly, EphA3 targeting by an anti EphA3 antibody reduced all
the MMEC angiogenesis-related functions in vitro. In conclusion, our findings
suggest that EphA3 plays an important role in MM angiogenesis.
PMID- 28415716
TI - Single nucleotide polymorphism rs3124599 in Notch1 is associated with the risk of
lung cancer in northeast Chinese non-smoking females.
AB - Lung cancer is one of the most common cancers and the main cause of cancer
related deaths. Notch1 might play a part in tumorigenesis of lung cancer. Here we
explored the relationship of three SNPs (rs3124599, rs3124607 and rs3124594) in
Notch1 with the risk and the survival of lung cancer in non-smoking females,
including 556 cases and 395 controls. Chi-square tests, logistic regression
analysis and crossover analysis were conducted to estimate the association
between SNPs and the risk of lung cancer and the interaction between SNPs and
environmental exposure. Survival analysis was conducted to explore the
association between SNPs and survival of lung cancer. The results demonstrated
that the polymorphism of rs3124599 was associated with the susceptibility of lung
cancer in recessive model (AA+AG vs. GG). Compared to the those with AA or AG
genotype, individuals with GG genotype had a 1.562-fold increased risk of lung
cancer (P = 0.023, OR = 1.562, 95% CI = 1.062-2.297). In stratified analysis, the
GG genotype of rs3124599 would increase the risk of small cell lung cancer (SCLC)
(P = 0.011, OR = 2.167, 95% CI = 1.193-3.396). However, no significant
interaction between rs3124599 and cooking oil fume exposure was observed either
in addictive model or multiplicative model. The results of survival analysis
showed there was no significant association between SNPs and prognosis of lung
cancer (P = 0.949 for rs3124599, P = 0.508 for rs3124607, P = 0.884 for
rs3124594). Our study might indicate that rs312599 in Notch1 may be a novel
biomarker for SCLC risk in Chinese non-smoking females.
PMID- 28415717
TI - The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent
apoptosis and sensitizes cancer cells to radiation.
AB - C-1311 is a small molecule, which has shown promise in a number of pre-clinical
and clinical studies. However, the biological response to C-1311 exposure is
complicated and has been reported to involve a number of cell fates. Here, we
investigated the molecular signaling which determines the response to C-1311 in
both cancer and non-cancer cell lines. For the first time we demonstrate that the
tumor suppressor, p53 plays a key role in cell fate determination after C-1311
treatment. In the presence of wild-type p53, cells exposed to C-1311 entered
senescence. In contrast, cells lines without functional p53 underwent mitotic
catastrophe and apoptosis. C-1311 also induced autophagy in a non-p53-dependent
manner. Cells in hypoxic conditions also responded to C-1311 in a p53-dependent
manner, suggesting that our observations are physiologically relevant. Most
importantly, we show that C-1311 can be effectively combined with radiation to
improve the radiosensitivity of a panel of cancer cell lines. Together, our data
suggest that C-1311 warrants further clinical testing in combination with
radiotherapy for the treatment of solid tumors.
PMID- 28415718
TI - Exosomal microRNAs isolated from plasma of mesenteric veins linked to liver
metastases in resected patients with colon cancer.
AB - Before reaching a peripheral vein (PV), miRNAs released by the tumor are diluted
and dispersed throughout the body or even retained in a specific organ. We
hypothesized that blood drawn from the tumor-draining vein could provide more
homogeneous information than blood drawn from the PV as that blood would contain
all the biomarkers released by the tumor before they reach a potential metastatic
site. We have profiled 754 miRNAs in 15 colon cancer plasma samples from the
tumor-draining vein, the mesenteric vein (MV), identifying 13 microRNAs
associated with relapse. The prognostic impact of these miRNAs were validated in
50 MV and 50 paired PV plasma samples of stage I-III colon cancer patients. Four
miRNAs, let-7g, miR-15b, miR-155 and miR-328, were found overexpressed in MV
compared to PV, and patients with high levels of those miRNAs in MV plasma had
shorter time to relapse. Interestingly, in patients developing liver metastases,
the exosomal cargo of miR-328 was much greater in MV than in PV plasma indicating
a possible role of miR-328 in the development of liver metastases. Our results
indicate that in colon cancer, the primary tumor releases high concentrations of
miRNAs through the MV, and some of them are contained in tumor derived exosomes.
PMID- 28415719
TI - Endosomal sorting and c-Cbl targeting of paxillin to autophagosomes regulate cell
matrix adhesion turnover in human breast cancer cells.
AB - Post-translational mechanisms regulating cell-matrix adhesion turnover during
cell locomotion are not fully elucidated. In this study, we uncovered an
essential role of Y118 site-specific tyrosine phosphorylation of paxillin, an
adapter protein of focal adhesion complexes, in paxillin recruitment to
autophagosomes to trigger turnover of peripheral focal adhesions in human breast
cancer cells. We demonstrate that the Rab-7 GTPase is a key upstream regulator of
late endosomal sorting of tyrosine118-phosphorylated paxillin, which is
subsequently recruited to autophagosomes via the cargo receptor c-Cbl.
Essentially, this recruitment involves a direct and selective interaction between
Y118-phospho-paxillin, c-Cbl, and LC3 and is independent from c-Cbl E3 ubiquitin
ligase activity. Interference with the Rab7-paxillin-autophagy regulatory network
using genetic and pharmacological approaches greatly impacted focal adhesion
stability, cell locomotion and progression to metastasis using a panel of human
breast cancer cells. Together, these results provide novel insights into the
requirement of phospho-site specific post-translational mechanism of paxillin for
autophagy targeting to regulate cell-matrix adhesion turnover and cell locomotion
in breast cancer cells.
PMID- 28415720
TI - The function of oxytocin: a potential biomarker for prostate cancer diagnosis and
promoter of prostate cancer.
AB - PURPOSE: To measure the level of oxytocin in serum and prostate cancer (PCa)
tissue and study its effect on the proliferation of PCa cells. RESULTS: Oxytocin
level in serum was significantly increased in PCa patients compared with the no
carcinoma individuals. Additionally, the levels of oxytocin and its receptor were
also elevated in the PCa tissue. However, no significant difference existed among
the PCa of various Gleason grades. Western blot analysis confirmed the previous
results and revealed an increased expression level of APPL1. MATERIALS AND
METHODS: The level of oxytocin in serum was measured by ELISA analysis. The
expression of oxytocin and its receptor in prostate was analyzed by
immunohistochemistry. The proliferation and apoptosis of PCa cells were assessed
by the Cell Counting Kit 8 (CCK8) assay, cell cycle analysis and caspase3
activity analysis, respectively. Western blot analysis was used for the detection
of PCNA, Caspase3 and APPL1 protein levels. CONCLUSIONS: Serum and prostatic
oxytocin levels are increased in the PCa subjects. Serum oxytocin level may be a
biomarker for PCa in the future. Oxytocin increases PCa growth and APPL1
expression.
PMID- 28415721
TI - Robust in-silico identification of cancer cell lines based on next generation
sequencing.
AB - Cancer cell lines (CCL) are important tools for cancer researchers world-wide.
However, handling of cancer cell lines is error-prone, and critical errors such
as misidentification and cross-contamination occur more often than acceptable.
Based on the fact that CCL today very often are sequenced (partly or entirely)
anyway as part of the studies performed, we developed Uniquorn, a computational
method that reliably identifies CCL samples based on variant profiles derived
from whole exome or whole genome sequencing. Notably, Uniquorn does neither
require a particular sequencing technology nor downstream analysis pipeline but
works robustly across different NGS platforms and analysis steps. We evaluated
Uniquorn by comparing more than 1900 CCL profiles from three large CCL libraries,
embracing 1585 duplicates, against each other. In this setting, our method
achieves a sensitivity of 97% and specificity of 99%. Errors are strongly
associated to low quality mutation profiles. The R-package Uniquorn is freely
available as Bioconductor-package.
PMID- 28415722
TI - Stat3 phosphorylation is required for embryonic stem cells ground state
maintenance in 2i culture media.
AB - Embryonic stem cells (ES cells) can be maintained its undifferentiated state with
feeder cells or LIF, which can activate Jak/Stat3 pathway. Recently, it has been
reported a new culture condition comprising serum-free medium with ERK and
GSK3beta inhibitors (2i) could drive ES cells into a state of pluripotency more
like inner cell mass (ICM) in mouse blastocysts called ground state. However,
although 2i could sustain ES cells self-renewal, LIF is routinely added. The
roles of Stat3 activation are still unclear now. Here we investigated whether
Jak/Stat3 might also contribute to the induction of ground state pluripotency. We
introduced a lentiviral construct with 7-repeat Stat3-binding sequence to drive
Renilla luciferase into ES cells, which can be used as a reporter to detect Stat3
activation by noninvasive bioluminescence imaging. Using this ES cells, we
investigated the role of Stat3 activation in ground state maintenance. The
results showed that Stat3 could be activated by 2i. Stattic, a chemical inhibitor
of Stat3 phosphorylation, could effectively inhibit Stat3 activation in ES cells.
When Stat3 activation was suppressed, ground state related genes were down
regulated, and ES cells could not be maintained the ground state pluripotency
even in 2i medium. All of these results indicate Stat3 activation is required in
ground state maintenance.
PMID- 28415723
TI - Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and
resulting overproduction of reactive oxygen species.
AB - Auranofin (AF) is an anti-arthritic drug considered for combined chemotherapy due
to its ability to impair the redox homeostasis in tumor cells. In this study, we
asked whether AF may in addition radiosensitize tumor cells by targeting
thioredoxin reductase (TrxR), a critical enzyme in the antioxidant defense system
operating through the reductive protein thioredoxin. Our principal findings in
murine 4T1 and EMT6 tumor cells are that AF at 3-10 MUM is a potent
radiosensitizer in vitro, and that at least two mechanisms are involved in TrxR
mediated radiosensitization. The first one is linked to an oxidative stress, as
scavenging of reactive oxygen species (ROS) by N-acetyl cysteine counteracted
radiosensitization. We also observed a decrease in mitochondrial oxygen
consumption with spared oxygen acting as a radiosensitizer under hypoxic
conditions. Overall, radiosensitization was accompanied by ROS overproduction,
mitochondrial dysfunction, DNA damage and apoptosis, a common mechanism
underlying both cytotoxic and antitumor effects of AF. In tumor-bearing mice, a
simultaneous disruption of the thioredoxin and glutathione systems by the
combination of AF and buthionine sulfoximine was shown to significantly improve
tumor radioresponse. In conclusion, our findings illuminate TrxR in cancer cells
as an exploitable radiobiological target and warrant further validation of AF in
combination with radiotherapy.
PMID- 28415724
TI - Pharmacological inhibition of Src kinase protects against acute kidney injury in
a murine model of renal ischemia/reperfusion.
AB - Activation of Src kinase has been implicated in the pathogenesis of acute brain,
liver, and lung injury. However, the role of Src in acute kidney injury (AKI)
remains unestablished. To address this, we evaluated the effects of Src
inhibition on renal dysfunction and pathological changes in a murine model of AKI
induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in
increased Src phosphorylation at tyrosine 416 (activation). Administration of
PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved
renal function and ameliorated renal pathological damage. PP1 treatment also
suppressed renal expression of neutrophil gelatinase-associated lipocalin and
reduced apoptosis in the injured kidney. Moreover, Src inhibition prevented
downregulation of several adherens and tight junction proteins, including E
cadherin, ZO-1, and claudins-1/-4 in the kidney after I/R injury as well as in
cultured renal proximal tubular cells following oxidative stress. Finally, PP1
inhibited I/R-induced renal expression of matrix metalloproteinase-2 and -9,
phosphorylation of extracellular signal-regulated kinases1/2, signal transducer
and activator of transcription-3, and nuclear factor-kappaB, and the infiltration
of macrophages into the kidney. These data indicate that Src is a pivotal
mediator of renal epithelial injury and that its inhibition may have a
therapeutic potential to treat AKI.
PMID- 28415725
TI - Stat3-positive tumor cells contribute to vessels neoformation in primary central
nervous system lymphoma.
AB - With the aim of elucidating the relationship between Stat3 expression and tumor
vessels abnormalities in the PCNLs, in this study we evaluated Stat3 and pStat3
expression by Real-time PCR and by immunohistochemistry in biopsy sections from
PCNSL patients. Correlations of the expression levels with the presence of
aberrant vessels were analyzed by confocal laser microscopy analysis, using FVIII
as endothelial cell marker, CD133 and nestin as cancer stem cell (CSC) marker,
CD20 as tumor cell marker, and Stat3. In addition, we investigated Stat3
mutations in lymphoma cells to clarify the role of the constitutive expression of
Stat3 and of its phosphorylated forms. Results showed that in PCNSL, putative
endothelial cells lining the vessels are heterogeneous, expressing FVIII/
pStat3/CD133 (presumably originally they are vascular progenitor cells), as well
as FVIII/CD20/CD133 (presumably originally they are tumor cells). Finally, we
detected a fraction of the FVIII+ endothelial cell that co-expressed Stat3
bearing a tetraploid karyotype, while no amplification signal for the Stat3 gene
was detected.
PMID- 28415727
TI - Further rationale for optimal combined modality treatments.
PMID- 28415726
TI - PGE2/EP3/SRC signaling induces EGFR nuclear translocation and growth through EGFR
ligands release in lung adenocarcinoma cells.
AB - Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in
both tumor and stromal cells supporting tumor progression. Here we demonstrate
that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2
promotes nuclear translocation of epidermal growth factor receptor (nEGFR),
affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS
and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear
localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are
required for the effect of PGE2 on nEGFR and downstream signaling activities.
PGE2 binds its bona fide receptor EP3 which by activating SRC family kinases,
induces ADAMs activation which, in turn, releases EGFR-ligands from the cell
membrane and promotes nEGFR. Amphiregulin (AREG) and Epiregulin (EREG) appear to
be involved in nEGFR promoted by the PGE2/EP3-SRC axis. Pharmacological
inhibition or silencing of the PGE2/EP3/SRC-ADAMs signaling axis or EGFR ligands
i.e. AREG and EREG expression abolishes nEGFR induced by PGE2. In conclusion,
PGE2 induces NSCLC cell proliferation by EP3 receptor, SRC-ADAMs activation, EGFR
ligands shedding and finally, phosphorylation and nEGFR. Since nuclear EGFR is a
hallmark of cancer aggressiveness, our findings reveal a novel mechanism for the
contribution of PGE2 to tumor progression.
PMID- 28415728
TI - Lipid degradation promotes prostate cancer cell survival.
AB - Prostate cancer is the most common male cancer and androgen receptor (AR) is the
major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2)
is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2
expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2
encodes for an enzyme involved in lipid metabolism, and we use multiple
metabolite profiling platforms and RNA-seq to show that inhibition of ECI2
expression leads to decreased glucose utilization, accumulation of fatty acids
and down-regulation of cell cycle related genes. In normal cells, decrease in
fatty acid degradation is compensated by increased consumption of glucose, and
here we demonstrate that prostate cancer cells are not able to respond to
decreased fatty acid degradation. Instead, prostate cancer cells activate
incomplete autophagy, which is followed by activation of the cell death response.
Finally, we identified a clinically approved compound, perhexiline, which
inhibits fatty acid degradation, and replicates the major findings for ECI2
knockdown. This work shows that prostate cancer cells require lipid degradation
for survival and identifies a small molecule inhibitor with therapeutic
potential.
PMID- 28415729
TI - Association between hOGG1 polymorphism rs1052133 and gastric cancer.
AB - PURPOSE: To conduct a comprehensive evaluation of the association of the human8
oxoguanine glycosylase 1 (hOGG1) gene polymorphism rs1052133 with gastric cancer
(GC) through a systematic review and meta-analysis of genetic association study.
RESULTS: A total of 15 articles from published papers were included in our
analysis. The meta-analyses for hOGG1 rs1052133, composed of 4024GC patients and
6022controls, showed low heterogeneity for the included populations in all the
genetic models, except for the Caucasian population under allelic genetic model,
the Asian population under addictive model and Caucasian population under
dominant model. The analyses of all the genetic models in overall pooled
populations did not identify any significant association between GC and hOGG1
rs1052133 (Allelic model: C vs. G , p = 0.746; Addictive model: CC vs. GG, p =
0.888; Recessive model: CC +GC vs. GG, p = 0.628; Dominant model: CC vs. GG+GC, p
= 0.147), even though stratified analyses were conducted in different ethnicities
under each genetic model. MATERIALS AND METHODS: All case-control association
studies on hOGG1 and GC reported up to December 15, 2016 in PubMed, Embase, Web
of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs)
and 95% confidence intervals (95% CIs) were calculated for single-nucleotide
polymorphism (SNP) using fixed- and random- effects models according to between
study heterogeneity. Publication bias analyses were conducted using Begg test.
CONCLUSIONS: This meta-analysis showed there was no association between hOGG1
rs1052133 and GC. Given the limited sample size, further investigations including
more ethnic groups are required to validate the association.
PMID- 28415730
TI - A polymorphism at IGF1 locus is associated with anemia.
AB - In vitro and in vivo studies suggest that IGF-1 has a role in erythropoiesis.
There is evidence that the rs35767 C/T polymorphism near IGF1 is associated with
plasma IGF-1 levels. We investigated the effect of this polymorphism on
hemoglobin (Hb) concentration and anemia. The study group comprised 3286 adult
Whites. The rs35767 polymorphism was screened using a TaqMan allelic
discrimination assay. The rs35767 polymorphism was not associated with age,
gender, BMI, waist circumference, smoking, blood pressure, plasma glucose, HbA1c,
type 2 diabetes, HOMA-IR, hsCRP, eGFR, and lipid profile. Erythrocyte
sedimentation rate (ESR), fibrinogen, and fasting insulin levels were
significantly lower in TT genotype carriers compared with C allele carriers. Hb
concentration was significantly higher in carriers of the TT genotype compared
with C allele carriers, and a lower proportion of TT carriers had anemia. As
compared with TT genotype carriers, those bearing the CC genotype had a 2.4-fold
higher risk of anemia (OR 2.40, 95%CI 1.19-4.82), and those with the CT genotype
had a 2.0-fold higher risk of anemia (OR 2.06, 95%CI 1.04-4.11). The association
remained significant when fasting insulin, eGFR, smoking, diabetes, ACE
inhibitors, sartans or diuretics treatments, use of metformin and pioglitazone
were added to the model, but its independence was not retained after inclusion of
fibrinogen and ESR values into the model. In conclusion, rs35767 TT allele
carriers exhibited significantly higher concentrations of Hb, and lower risk of
anemia compared with C allele carriers supporting the idea that IGF-1 plays a
role in erythropoiesis homeostasis.
PMID- 28415734
TI - Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract
cancers: a systematic review and meta-analysis.
AB - BACKGROUND: Inflammation was considered to perform crucial roles in the
development and metastasis of malignancies. A heightened neutrophil-lymphocyte
ratio has been described to be associated with detrimental survivals in different
malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte
ratio on survivals in biliary tract cancer. The review evaluated the prognostic
value of neutrophil-lymphocyte ratio in biliary tract cancer. METHODS: MEDLINE,
the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically
searched for relevant articles. Associations between neutrophil-lymphocyte ratio
and long-term outcomes were expressed as the hazard ratios and 95% confidence
intervals. The odds ratio was utilized to assess the association between
neutrophil-lymphocyte ratio and clinicopathological parameters. RESULTS: Fourteen
studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high
pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low
pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened
pretreatment neutrophil-lymphocyte ratio was significantly associated with
detrimental overall survival and relapse free survival for biliary tract cancer
patients. In addition, elevated neutrophil-lymphocyte ratio was positively
correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and
greater lymph node involvement. CONCLUSION: This meta-analysis marked that an
increased pretreatment neutrophil-lymphocyte ratio was significantly linked with
detrimental long-term outcomes and clinicopathological parameters for patients
with biliary tract cancer.
PMID- 28415735
TI - Salicylate *Phenanthroline copper (II) complex induces apoptosis in triple
negative breast cancer cells.
AB - In this study, we investigated anti-tumor activity and associated molecular
mechanism of action of Salicylate ?Phenanthroline Copper (II) Complex in triple
negative breast cancer. Salicylate ?Phenanthroline Copper (II) Complex inhibited
the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20)
and induced apoptosis in a concentration-dependent manner. The effect was more
profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines.
Western blot showed that the expression of the apoptosis-related protein Bcl-2,
Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with
Salicylate ?Phenanthroline Copper (II) Complex. In vivo, Salicylate
?Phenanthroline Copper (II) Complex administration significantly attenuated tumor
growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and
survivin were reduced as measured by immunohistochemical staining. These data
suggest that Salicylate ?Phenanthroline Copper (II) Complex is a promising novel
therapeutic drug for triple-negative breast cancer and warrants further study.
PMID- 28415736
TI - The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment
of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty
liver disease.
AB - BACKGROUND/AIM: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a
novel serum model, which was reported more accurate than aspartate transaminase
to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)
for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West
Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis
in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease
(NAFLD). RESULTS: Of 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were
classified as having significant fibrosis, severe fibrosis and cirrhosis,
respectively. To predict significant fibrosis, the AUROC of GPR was higher than
that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To
predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89
vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no
difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p =
0.104). MATERIALS AND METHODS: 131 patients with CHB-NAFLD were included, and the
diagnostic performances of GPR, APRI and FIB-4 were compared by receiver
operating characteristic (ROC) curves and the area under ROC curves (AUROCs).
CONCLUSIONS: The GPR could be used as a non-invasive marker to predict liver
fibrosis and cirrhosis in CHB-NAFLD individuals.
PMID- 28415737
TI - Peroxynitrite dominates sodium nitroprusside-induced apoptosis in human
hepatocellular carcinoma cells.
AB - This study aims to explore which radicals dominate sodium nitroprusside (SNP)
induced cytotoxicity in human hepatocellular carcinoma (HCC) cells (HepG2 and
Hep3B). Exposure of SNP to cell medium produced abundant nitric oxide (NO),
superoxide anion (O2*-), hydrogen peroxide (H2O2) and iron ions. SNP potently
induced caspases activation, mitochondrial membrane permeabilization and
apoptosis in HCC cells. In Hep3B cells, pretreatment with NO scavenger (PTIO) did
not prevent SNP-induced cytotoxicity. However, in HepG2 cells, SNP-induced
cytotoxicity was prevented significantly by pretreatment with PTIO and O2*-
scavenger, and especially was almost completely blocked by pretreatment with
FeTPPS (peroxynitrite scavenger). In contrast, although H2O2 scavenger potently
scavenged SNP-induced H2O2 production, it did not prevent SNP-induced
cytotoxicity in HepG2 cells. In addition, pretreatment with DFO (iron ions
chelator) and iron-saturated DFO respectively completely prevented SNP-induced
cytotoxicity in HepG2 cells. Collectively, peroxynitrite from the reaction
between NO and O2*- elicited from SNP dominates the SNP-induced apoptosis of
HepG2 cells, in which both iron ions and H2O2 are not involved.
PMID- 28415738
TI - Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances
the efficacy of near-infrared targeted photodynamic therapy in esophageal
adenocarcinoma cell lines.
AB - Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year
survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR
tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to
selectively treat malignant cells. In this in vitro report we demonstrate the
applicability of antibody-based NIR-tPDT in esophageal adenocarcinoma (EAC),
using the phototoxic compounds cetuximab-IRDye700DX and trastuzumab-IRDye700DX,
targeting respectively epidermal growth factor receptor 1 (EGFR) and 2 (HER2).
Furthermore, we demonstrate that NIR-tPDT can be made more effective by tyrosine
kinase inhibitor (TKI) induced growth receptor upregulation. Together, these
results unveil a novel strategy for non-invasive EAC treatment, and by
pretreatment-induced receptor upregulation its future clinical application may be
optimized.
PMID- 28415739
TI - High TGF-beta1 expression predicts poor disease prognosis in hepatocellular
carcinoma patients.
AB - Transforming growth factor beta (TGF-beta) promotes the pathogenesis of
hepatocellular carcinoma (HCC). We evaluated the associations between TGF-beta1
expression and clinicopathological parameters in HCC patients from The Cancer
Genome Atlas (TCGA), as well as the prognostic power of TGF-beta1 expression.
Eligible studies were retrieved from several databases, and effects (hazard
ratios (HRs) with 95% confidence intervals (CIs)) for overall survival (OS),
disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free
survival (MFS), and progression-free survival (PFS) were pooled to assess the
prognostic ability of TGF-beta1 expression in HCC patients. Twelve qualified
articles and our TCGA data comprising 2,021 HCC patients were incorporated. In
the TCGA analysis, HCC patients with higher TGF-beta1 expression presented a
shorter OS than those with lower TGF-beta1 expression (HR = 1.42, p < 0.05). In
the meta-analysis, univariate analyses showed that HCC patients with higher TGF
beta1 expression had a shorter OS (pooling HR = 1.71, p < 0.01) and
DFS/RFS/MFS/PFS (pooling HR = 1.60, p < 0.01) than those with lower TGF-beta1
expression. In conclusion, our results suggested that high TGF-beta1 expression
promotes a poor prognosis in HCC patients.
PMID- 28415740
TI - Development and validation of nomograms for predicting survival in patients with
non-metastatic colorectal cancer.
AB - BACKGROUND: This study aimed to develop nomograms for predicting survival in
patients with non-metastatic colorectal cancer (CRC). RESULTS: On multivariate
analyses of the derivation set, the nomograms for OS and CSS shared common
significant prognostic factors: age, first-degree relative cancer history,
differentiation grade, vessels/nerves invasion, TNM stage, CEA, CA19-9 and PNI.
The nomograms displayed good accuracy in predicting OS and CSS, with C-indexes of
0.75 and 0.76, respectively. The calibration plots also showed an excellent
agreement between the predicted and observed survival probabilities. Furthermore,
the predictive accuracy of the nomograms was confirmed in the validation set,
with C-indexes of 0.79 and 0.83 for OS and CSS, respectively. MATERIALS AND
METHODS: On the basis of data from 822 patients with resected non-metastatic CRC,
nomograms for predicting overall survival (OS) and cancer-specific survival (CSS)
were established using Cox regression model. The predictive performance of the
nomograms was assessed by concordance index (C-index) and calibration plot. An
independent external cohort of 171 patients was used to validate the nomograms.
CONCLUSIONS: We developed and validated two nomograms for patients with non
metastatic CRC, which could provide individual prediction of OS and CSS with high
accuracy.
PMID- 28415743
TI - Survival differences of CIMP subtypes integrated with CNA information in human
breast cancer.
AB - CpG island methylator phenotype of breast cancer is associated with widespread
aberrant methylation at specified CpG islands and distinct patient outcomes.
However, the influence of copy number contributing to the prognosis of tumors
with different CpG island methylator phenotypes is still unclear. We analyzed
both genetic (copy number) and epigenetic alterations in 765 breast cancers from
The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy
number and methylation status evaluation. The gene panel identified two groups
corresponding to distinct copy number profiles. In status of mere-loss copy
number, patients were faced with a greater risk if they presented a higher CpG
islands methylation pattern in biomarker panels. But for samples presenting
merely-gained copy number, higher methylation level of CpG islands was associated
with improved viability. In all, the integration of copy number alteration and
methylation information enhanced the classification power on prognosis. Moreover,
we found the molecular subtypes of breast cancer presented different
distributions in two CpG island methylation phenotypes. Generated by the same set
of human methylation 450K data, additional copy number information could provide
insights into survival prediction of cancers with less heterogeneity and might
help to determine the biomarkers for diagnosis and treatment for breast cancer
patients in a more personalized approach.
PMID- 28415741
TI - Enhancement of radiosensitivity by the novel anticancer quinolone derivative
vosaroxin in preclinical glioblastoma models.
AB - PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The
activity of vosaroxin, a first-in-class anticancer quinolone derivative that
intercalates DNA and inhibits topoisomerase II, was investigated in GBM
preclinical models as a single agent and combined with radiotherapy (RT).
RESULTS: Vosaroxin showed antitumor activity in clonogenic survival assays, with
IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments
exhibited significantly higher gammaH2Ax levels compared with controls. In
xenograft models, vosaroxin reduced tumor growth and showed enhanced activity
with RT; vosaroxin/RT combined was more effective than temozolomide/RT.
Vosaroxin/RT triggered rapid and massive cell death with characteristics of
necrosis. A minor proportion of treated cells underwent caspase-dependent
apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced
autophagy, increasing necrosis. This was associated with increased recruitment of
granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells.
Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin.
Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS)
significantly compared with RT, vosaroxin alone, temozolomide, and
temozolomide/RT in the U251-luciferase orthotopic model. MATERIALS AND METHODS:
Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined
with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in
U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in
orthotopic intrabrain models using luciferase-transfected U251 cells by
bioluminescence and magnetic resonance imaging. CONCLUSIONS: Vosaroxin
demonstrated significant activity in vitro and in vivo in GBM models, and showed
additive/synergistic activity when combined with RT in O6-methylguanine
methyltransferase-negative and -positive cell lines.
PMID- 28415744
TI - EMT-like circulating tumor cells in ovarian cancer patients are enriched by
platinum-based chemotherapy.
AB - BACKGROUND: Assuming that tumor cell dissemination requires a shift to a
mesenchymal phenotype, we analyzed the incidence of epithelial-to-mesenchymal
transition (EMT)-like circulating tumor cells (CTCs) in ovarian cancer patients
and inquired, how their molecular phenotypes respond to platinum-based
chemotherapy and influence outcome. RESULTS: Before surgery, overall detection
rate for epithelial CTCs was 18%. EMT-like CTCs were more frequently observed
(30%) and were mutually exclusive to epithelial CTCs in the majority of patients
(82%). After chemotherapy, EMT-like CTCs increased up to 52%, accompanied by the
"de novo" emergence of PI3Kalpha+/Twist+ EMT-like CTCs. Before surgery, PI3K+ EMT
like CTCs in combination with epithelial CTCs indicated decreased OS (p = 0.02)
and FIGO I-III patients with residual tumor burden after surgery were more likely
to be positive for EMT-like CTCs after chemotherapy (p = 0.02). In the latter
group, epithelial CTCs alone significantly correlated with decreased PFS and OS
(p = 0.02, p = 0.002), supported by an additional inclusion of PI3K+ CTCs (OS, p
= 0.001). MATERIALS AND METHODS: Blood samples of 91 ovarian cancer patients
before surgery and 31 matched samples after adjuvant chemotherapy were evaluated
for CTCs with the AdnaTest ovarian cancer and EMT-1, analyzing the epithelial
associated transcripts EpCAM, Muc-1 and CA125 and the EMT-associated transcripts
PI3Kalpha, Akt-2 and Twist. CONCLUSIONS: Platinum-based chemotherapy seems to
select for EMT-like CTCs in ovarian cancer patients and provokes a shift towards
PI3Kalpha and Twist expressing CTCs, which may reflect clonal tumor evolution
towards therapy resistance. It has to be determined, whether this CTC subgroup
may serve as a biomarker to identify patients at high risk.
PMID- 28415745
TI - Comparative study of cisplatin-based definitive concurrent chemoradiotherapy with
S-1 versus paclitaxel for unresectable locally advanced esophageal squamous cell
carcinoma.
AB - This study compared the efficiency and safety of definitive concurrent
chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus
Cisplatin (CS) in unresectable locally advanced esophageal squamous cell
carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients
were retrospectively reviewed. We performed a propensity score matching analysis;
41 patients treated with the CS regimen were matched 1:1 to patients who received
the TP regimen. Patient- and disease-related characteristics were well-balanced
between the two groups. The CS group showed significantly better treatment
compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49
days, P = 0.025) over the TP group during the CCRT course. The complete response
rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1-
and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4%
compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and
3-year progression-free survival (PFS) rates in the TP group were 51.2% and
24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The
incidence of severe and total neutropenia in the TP group was significantly
higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate
analysis revealed that T stage and the complete response rate were strong
prognostic factors associated with OS and PFS. In conclusion, both treatment
regimens yielded satisfactory survival outcomes, but the CS regimen could
significantly improve treatment compliance, reduce hematological toxicities and
lengths of hospital stay. Future prospective studies in large cohorts are highly
warranted to confirm the findings in our report.
PMID- 28415746
TI - Epigenetic up-regulation of ribosome biogenesis and more aggressive phenotype
triggered by the lack of the histone demethylase JHDM1B in mammary epithelial
cells.
AB - The alterations of ribosome biogenesis and protein synthesis play a direct role
in the development of tumors. The accessibility and transcription of ribosomal
genes is controlled at several levels, with their epigenetic regulation being one
of the most important. Here we explored the JmjC domain-containing histone
demethylase 1B (JHDM1B) function in the epigenetic control of rDNA transcription.
Since JHDM1B is a negative regulator of gene transcription, we focused on the
effects induced by JHDM1B knock-down (KD). We studied the consequences of stable
inducible JHDM1B silencing in cell lines derived from transformed and
untransformed mammary epithelial cells. In these cellular models, prolonged
JHDM1B downregulation triggered a surge of 45S pre-rRNA transcription and
processing, associated with a re-modulation of the H3K36me2 levels at rDNA loci
and with changes in DNA methylation of specific CpG sites in rDNA genes. We also
found that after JHDM1B KD, cells showed a higher ribosome content: which were
engaged in mRNA translation. JHDM1B KD and the consequent stimulation of
ribosomes biogenesis conferred more aggressive features to the tested cellular
models, which acquired a greater clonogenic, staminal and invasive potential.
Taken together, these data indicate that the reduction of JHDM1B leads to a more
aggressive cellular phenotype in mammary gland cells, by virtue of its negative
regulatory activity on ribosome biogenesis.
PMID- 28415747
TI - Comparison of Gadolinium-enhanced MRI and 18FDG PET/PET-CT for the diagnosis of
brain metastases in lung cancer patients: A meta-analysis of 5 prospective
studies.
AB - OBJECTIVE: We undertook this meta-analysis to compare the significance of
Gadolinium-enhanced MRI and 18FDG PET/PET-CT for diagnosing brain metastases of
lung cancer patients. RESULTS: Five articles comprising 941 patients were
included for analysis. The sensitivities with 95% confidence interval for PET/PET
CT and MRI were 0.21 (0.13 - 0.32) and 0.77 (95% CI = 0.60 - 0.89), specificities
were 1.00 (0.99 - 1.00) and 0.99 (0.97 - 1.00), and the areas under curve were
0.98 (0.96 - 0.89) and 0.97 (0.96 - 0.98). MATERIALS AND METHODS: A computerized
literature search of studies was conducted in the Pubmed and Embase databases.
Meta-analysis methods were used to calculate the sensitivities, specificities,
likelihood ratios ratios, diagnostic odd ratios, and areas under summary receiver
operating characteristic curves for PET/PET-CT and MRI, respectively.
CONCLUSIONS: The analysis suggested Gadolinium-enhanced MRI had higher
sensitivity than 18FDG PET/PET-CT for the diagnosis of brain metastases in lung
cancer. MRI may provide additional information to PET-CT for diagnosing brain
metastatic lesions.
PMID- 28415748
TI - The Spi1/PU.1 transcription factor accelerates replication fork progression by
increasing PP1 phosphatase in leukemia.
AB - Oncogenes trigger replicative stress that can lead to genetic instability, which
participates in cancer progression. Thus, determining how cells cope with
replicative stress can help our understanding of oncogenesis and lead to the
identification of new antitumor treatment targets. We previously showed that
constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads
to pre-leukemic cells that have a shortened S phase duration with an increased
replication fork speed and increased mutability in the absence of DNA breaks.
Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a
low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence
that this is not due to negative control of its primary kinase ATR. Notably, we
found that the expression of the CHK1 phosphatase PP1alpha is increased in
Spi1/PU.1-overexpressing cells. By exogenously modulating its activity, we
demonstrate that PP1alpha is required to maintain CHK1 in a dephosphorylated
state and, more importantly, that it is responsible for the accelerated
replication fork progression in Spi1/PU.1-overexpressing cells. These results
identify a novel pathway by which an oncogene influences replication in the
absence of DNA damage.
PMID- 28415749
TI - hMAGEA2 promotes progression of breast cancer by regulating Akt and Erk1/2
pathways.
AB - Breast cancer is the most abundant cancer worldwide and a severe problem for
women. Notably, breast cancer has a high mortality rate, mainly because of tumor
progression and metastasis. Triple-negative breast cancer (TNBC) is highly
progressive and lacks the expression of estrogen receptor (ER), progesterone
receptor (PR), and human epidermal growth factor receptor 2 (HER2). Therefore,
there are no established therapeutic targets against TNBC. In this study, we
investigated whether the expression of human melanoma-associated antigen A2
(MAGEA2) is associated with TNBC. We found that hMAGEA2 is significantly
overexpressed in human TNBC tissues; we also observed oncogenic properties using
TNBC cell lines (MDA-MB-231 and MDA-MB-468). The overexpression of hMAGEA2 in MDA
MB-231 cell line showed dramatically increased cellular proliferation, colony
formation, invasion, and xenograft tumor formation and growth. Conversely,
knockdown of hMAEGA2 in MDA-MB-468 cell line suppressed cellular proliferation,
colony formation, and xenograft tumor formation. Additionally, we showed that
hMAGEA2 regulated the activation of Akt and Erk1/2 signaling pathways. These data
indicate that hMAGEA2 is important for progression of TNBC and may serve as a
novel molecular therapeutic target.
PMID- 28415750
TI - Xanthohumol induces paraptosis of leukemia cells through p38 mitogen activated
protein kinase signaling pathway.
AB - Xanthohumol as a natural polyphenol demonstrates an anticancer activity, but its
underlying mechanism remains unclear. In this study, we showed that xanthohumol
(XN) induces paraptosis of leukemia cells. The paraptosis is one cell death which
is characterized by dilation of the endoplasmic reticulum and/or mitochondria.
The results demonstrated that XN treatment significantly inhibited cell
proliferation and triggered extensive cytoplasmic vacuolation of HL-60 leukemia
cells, but it did not cause the cleavage of caspase-3 protein or apoptosis. In
contrast, XN treatment resulted in LC3-II accumulation through blocking of
autophagosome maturation. Interestingly, the induction of cytoplasmic
vacuolization by XN is not associated with autophagy modulated by XN, therefore,
XN-induced cell death of HL-60 leukemia cells is not the classical apoptotic cell
death. Intriguingly, XN treatment triggered the dilatation of endoplasma
reticulum (ER) and induced ER stress by upregulating C/EBP homologous protein and
unfolded protein response regulator Grp78/Bip. Furthermore, XN treatment
triggered p38 mitogen activated protein kinase and its specific inhibitor
inhibited the paraptosis of HL-60 leukemia cells by XN. In conclusion, we for the
first time demonstrated that XN treatment can induce paraptosis of leukemia cells
through activation of p38 MAPK signaling.
PMID- 28415751
TI - Gene-gene interaction between PPARG and CYP1A1 gene on coronary artery disease in
the Chinese Han Population.
AB - AIMS: To observe the influence of the peroxisome proliferator-activator receptor
G (PPAR-G) gene and cytochrome P4501A1 (CYP1A1) single-nucleotide polymorphisms
(SNPs), and interactions among several SNPs on coronary artery disease (CAD)
risk. METHODS: A total of 1106 participants (including 583 males and 523 females)
including 550 CAD patients and 556 control subjects were recruited in this study,
and the mean age for these participants was 55.5 +/- 11.8 years old. Logistic
regression was used to observe association of SNP within PPARG and CYP1A1 with
CAD risk and GMDR model was used to screen the best interaction combinations.
RESULTS: CAD susceptibility was higher in those with homozygous mutant of
rs10865710, rs1805192 and rs4646903 than those with wild-type homozygotes, OR
(95%CI) were 1.47 (1.15-1.92), 1.69 (1.27-2.09) and 1.72 (1.35-2.32),
respectively. We also found a significant two-locus model involving rs1805192 and
rs4646903 (p = 0.0107), and the cross-validation consistency of this locus model
was 10 of 10, the testing accuracy of this model is 62.17%. Logistic regression
shown that CAD risk was the highest in those with rs1805192- Pro/Ala or Ala/Ala
and rs4646903- AG+GG genotype, and was lowest in those with rs1805192- Pro/ Pro
and rs4646903- AA genotype, OR(95%CI) = 3.56 (1.91-5.42). CONCLUSIONS:
Polymorphism in rs10865710, rs1805192 and rs4646903 and interaction between
rs1805192 and rs4646903 were related with increased CAD susceptibility.
PMID- 28415752
TI - Correlation between facial morphology and gene polymorphisms in the Uygur youth
population.
AB - Human facial morphology varies considerably among individuals and can be
influenced by gene polymorphisms. We explored the effects of single nucleotide
polymorphisms (SNPs) on facial features in the Uygur youth population of the
Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers,
and 10 SNPs previously associated with variations in facial physiognomy were
genotyped. In parallel, 3D images of the subjects' faces were obtained using
grating facial scanning technology. After delimitation of 15 salient landmarks,
the correlation between SNPs and the distances between facial landmark pairs was
assessed. Analysis of variance revealed that ENPP1 rs7754561 polymorphism was
significantly associated with RAla-RLipCn and RLipCn-Sbn linear distances (p =
0.044 and p = 0.012, respectively) as well as RLipCn-Stm curve distance (p =
0.042). The GHR rs6180 polymorphism correlated with RLipCn-Stm linear distance (p
= 0.04), while the GHR rs6184 polymorphism correlated with RLipCn-ULipP curve
distance (p = 0.047). The FGFR1 rs4647905 polymorphism was associated with LLipCn
Nsn linear distance (p = 0.042). These results reveal that ENPP1 and FGFR1
influence lower anterior face height, the distance from the upper lip to the
nasal floor, and lip shape. FGFR1 also influences the lower anterior face height,
while GHR is associated with the length and width of the lip.
PMID- 28415753
TI - High mobility group box 1 antagonist limits metastatic seeding in the lungs via
reduction of cell-cell adhesion.
AB - Metastatic spread is the leading cause for cancer-related mortality, with the
lungs being a major site for metastatic seeding. Available therapies for patients
with metastatic disease are extremely limited. Therefore, there is a desperate
need for new strategies to prevent or limit metastatic dissemination and treat
existing metastases. The metastatic cascade is highly complex and is affected by
multiple factors related to both tumor cells themselves and the microenvironment
in the future site of metastasis. We hypothesized that modifying the lung
microenvironment by blocking central ubiquitous signals may affect metastatic
seeding in the lungs. Given the high basal levels of the Receptor for Advanced
Glycation End products (RAGE) in the pulmonary tissue, and its pro-inflammatory
properties, we investigated the consequences of interfering with its ligand; High
Mobility Group Box 1 (HMGB1). To this end, we tested the effect of Carbenoxolone,
an HMGB1 antagonist, on primary tumor growth and metastatic progression in
several murine tumor models. We show that antagonizing HMGB1 prevents the
adhesion and colonization of cancer cells in the lungs through the reduction of
their adhesion and cell-cell interaction both in vitro and in vivo. We
demonstrated that these activities are mediated by downregulation of the adhesion
molecule Intercellular Adhesion Molecule 1 (ICAM1) and ultimately result in
reduced metastatic burden. Carbenoxolone decreases significantly lung metastases
formation and can be used potentially as prophylactic therapy for metastatic
diseases.
PMID- 28415754
TI - Gene-modified NK-92MI cells expressing a chimeric CD16-BB-zeta or CD64-BB-zeta
receptor exhibit enhanced cancer-killing ability in combination with therapeutic
antibody.
AB - Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated
immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC)
mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was
derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor
cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually
mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based
immunotherapy to cancer treatment, we designed and generated two chimeric
receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins.
The construct includes the low-affinity Fc receptor CD16 (158F) or the high
affinity Fc receptor CD64, with the addition of the CD8a extracellular domain,
CD28 transmembrane domains, two costimulatory domains (CD28 and 4-1BB), and the
signaling domain from CD3zeta. The resulting chimeric receptors, termed CD16-BB
zeta and CD64-BB-zeta, were used to generate modified NK-92MI cells expressing
the chimeric receptor, which were named NK-92MIhCD16 and NK-92MIhCD64 cells,
respectively. We found that NK-92MIhCD16 and NK-92MIhCD64 cells significantly
improved cytotoxicity against CD20-positive non-Hodgkin's lymphoma cells in the
presence of rituximab. These results suggest that the chimeric receptor
expressing NK-92MI cells may enhance the clinical responses to currently
available anticancer monoclonal antibodies.
PMID- 28415756
TI - Human melanoma cells resistant to MAPK inhibitors can be effectively targeted by
inhibition of the p90 ribosomal S6 kinase.
AB - The clinical availability of small molecule inhibitors specifically targeting
mutated BRAF marked a significant breakthrough in melanoma therapy. Despite a
dramatic anti-tumour activity and improved patient survival, rapidly emerging
resistance, however, greatly limits the clinical benefit. The majority of the
already described resistance mechanisms involve a reactivation of the MAPK
signalling pathway. The p90 ribosomal S6 kinase (RSK), a downstream effector of
the MAPK signalling cascade, has been reported to enhance survival of melanoma
cells in response to chemotherapy. Here, we can show that RSK activity is
significantly increased in human melanoma cells with acquired resistance to the
BRAFV600E/K inhibitor vemurafenib. Interestingly, inhibition of RSK signalling
markedly impairs the viability of vemurafenib resistant melanoma cells and is
effective both in two-dimensional and in three-dimensional culture systems,
especially in a chronic, long-term application. The effect of RSK inhibition can
be partly replicated by downregulation of the well-known RSK target, Y-box
binding protein 1 (YB-1). Intriguingly, RSK inhibition also retains its efficacy
in melanoma cells with combined resistance to vemurafenib and the MEK inhibitor
trametinib. These data suggest that active RSK signalling might be an attractive
novel therapeutic target in melanoma with acquired resistance to MAPK pathway
inhibitors.
PMID- 28415755
TI - Mitochondrial matrix chaperone and c-myc inhibition causes enhanced lethality in
glioblastoma.
AB - Malignant gliomas display high levels of the transcription factor c-myc and
organize a tumor specific chaperone network within mitochondria. Here, we show
that c-myc along with mitochondrial chaperone inhibition displays massive tumor
cell death. Inhibition of mitochondrial matrix chaperones and c-myc was
established by utilizing genetic as well as pharmacological approaches.
Bromodomain and extraterminal (BET) family protein inhibitors, JQ1 and OTX015,
were used for c-myc inhibition. Gamitrinib was applied to interfere with
mitochondrial matrix chaperones. A xenograft model was used to determine the in
vivo efficacy. Combined inhibition of c-myc and mitochondrial matrix chaperones
led to a synergistic reduction of cellular proliferation (CI values less than 1)
in established glioblastoma, patient-derived xenograft and stem cell-like glioma
cultures. The combinatorial treatment of BET inhibitors and Gamitrinib elicited
massive apoptosis induction with dissipation of mitochondrial membrane potential
and activation of caspases. Mechanistically, BET-inhibitors and Gamitrinib
mediated a pronounced integrated stress response with a PERK-dependent up
regulation of ATF4 and subsequent modulation of Bcl-2 family of proteins with
down-regulation of Mcl-1 and its interacting partner, Usp9X, and an increase in
pro-apoptotic Noxa. Blocking ATF4 by siRNA attenuated Gamitrinib/BET inhibitor
mediated increase of Noxa. Knockdown of Noxa and Bak protected from the
combinatorial treatment. Finally, the combination treatment of Gamitrinib and
OTX015 led to a significantly stronger reduction of tumor growth as compared to
single treatments in a xenograft model of human glioma without induction of
toxicity. Thus, Gamitrinib in combination with BET-inhibitors should be
considered for the development for clinical application.
PMID- 28415757
TI - An absence of platelet activation following thalidomide treatment in vitro or in
vivo.
AB - Increased risk of thromboembolism and platelet hyperreactivity has been reported
in patients receiving thalidomide therapy. Whether thalidomide induces platelet
activation directly or through other factors remains unclear. The aim of this
study was to evaluate the effect of thalidomide on platelet activation under
resting conditions in vitro and in vivo. Isolated human or mouse platelets were
treated with different concentrations of thalidomide (10, 50 and 100 MUg/ml) for
60 min at 37 degrees C followed by analysis of platelet surface expression of
platelet receptors GPIbalpha, GPVI, alphaIIbbeta3 and P-selectin, and PAC-1 or
fibrinogen binding, by flow cytometry and collagen- or ADP-induced platelet
aggregation. In addition, thalidomide (200 mg/kg) was intraperitoneally injected
into mice for analysis of the effect of thalidomide on platelet activation in
vivo. No increased expression of P-selectin, PAC-1 or fibrinogen binding was
observed in either human and mouse platelets after thalidomide treatment in vitro
for 60 min at 37oC. Thalidomide treatment also did not affect expression of
GPIbalpha, GPVI or alphaIIbbeta3, nor did it affect collagen- or ADP-induced
platelet aggregation at threshold concentrations. However, while mice injected
with thalidomide displayed no increased surface expression of platelet P-selectin
or alphaIIbbeta3, there was a significantly shortened tail bleeding time,
thrombin time, prothrombin time together with higher levels of Factor IX and
fibrinogen. In conclusion, thalidomide at therapeutic doses does not directly
induce platelet activation under resting conditions in vitro or in vivo, but
results in increased procoagulant activity, which could explain the thalidomide
dependent prothrombotic tendency in patients.
PMID- 28415758
TI - Differential microRNA expression profiling in primary tumors and matched liver
metastasis of patients with colorectal cancer.
AB - BACKGROUND: Liver metastasis is common in patients with colorectal cancer (CRC),
and is correlated with poor outcome. MicroRNAs (miRNAs) are small non-coding RNAs
involved in cancer development and progression, but their role in CRC liver
metastasis has not been extensively investigated. RESULTS: Thirteen miRNAs were
deregulated in pCRCs compared to their matched liver metastases. Seventeen miRNAs
were chosen for validation, which confirmed significantly reduced expression of
miR-99b-5p, miR-377 and miR-200c and increased expression of miR-196b-5p in the
tissue of liver metastasis. Furthermore, miR-200c and miR-196b-5p were positively
correlated with shorter overall survival in pCRC patients with liver metastasis.
MATERIALS AND METHODS: Firstly, affymetrix microarrays involving 1036 miRNAs were
performed in two pairs of primary CRCs (pCRCs) and their matched liver
metastases. Secondly, validation of the results was carried out on an independent
cohort of 48 pairs of pCRCs and matched liver metastases using quantitative real
time polymerase chain reaction assay. CONCLUSIONS: We discovered a pCRC liver
metastasis-specific miRNA panel including miR-377, miR-99b-5p, miR-200c and miR
196b-5p through intensive validation. These miRNAs may function as prognostic
factors in patients with metastatic CRC.
PMID- 28415759
TI - KSHV co-infection down-regulates HPV16 E6 and E7 from cervical cancer cells.
AB - High-risk human papillomavirus (HPV) infection is the etiological agent of some
malignancies such as cervical, oral and oropharyngeal cancers. Kaposi sarcoma
associated herpesvirus (KSHV) represents a principal causative agent of several
human cancers arising in those immunocompromised patients. Interestingly, KSHV
DNA has been detected in the oral cavity and the female genital tract, although
its detection rate in cervical samples is very low and few reports are about
KSHV/HPV co-infection. Therefore, it remains unclear about the role of KSHV co
infection in the development of HPV-related neoplasias. In the current study, we
report that HPV16-integrated cervical cancer cell-line SiHa is susceptible to
KSHV latent infection and replication. We also have found that KSHV infection or
viral latent proteins are capable of reducing HPV16 E6/E7 expression through the
manipulation of cellular microRNA function. Array analysis indicates that KSHV
infection induces some inflammatory cytokines/chemokines production as well as up
regulates a series of interferon-induced genes expression, which may facilitate
host immune defense system attacking these co-infected cells and clearance of
viruses. Together, our data have provided possible explanations for very low
detection rate of KSHV shedding as well as of KSHV/HPV co-infection in cervical
samples and/or cervical cancer cells.
PMID- 28415760
TI - Binding of galectin-1 to integrin beta1 potentiates drug resistance by promoting
survivin expression in breast cancer cells.
AB - Galectin-1 is a beta-galactoside binding protein secreted by many types of
aggressive cancer cells. Although many studies have focused on the role of
galectin-1 in cancer progression, relatively little attention has been paid to
galectin-1 as an extracellular therapeutic target. To elucidate the molecular
mechanisms underlying galectin-1-mediated cancer progression, we established
galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA)
against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB
231 and Hs578T. Ablation of galectin-1 expression decreased cell proliferation,
migration, invasion, and doxorubicin resistance. We found that these effects were
caused by decreased galectin-1-integrin beta1 interactions and suppression of the
downstream focal adhesion kinase (FAK)/c-Src pathway. We also found that
silencing of galectin-1 inhibited extracellular signal-regulated kinase
(ERK)/signal transducer and activator of transcription 3 (STAT3) signaling,
thereby down-regulating survivin expression. This finding implicates STAT3 as a
transcription factor for survivin. Finally, rescue of endogenous galectin-1 knock
down and recombinant galectin-1 treatment both recovered signaling through the
FAK/c-Src/ERK/STAT3/survivin pathway. Taken together, these results suggest that
extracellular galectin-1 contributes to cancer progression and doxorubicin
resistance in TNBC cells. These effects appear to be mediated by galectin-1
induced up-regulation of the integrin beta1/FAK/c-Src/ERK/STAT3/survivin pathway.
Our results imply that extracellular galectin-1 has potential as a therapeutic
target for triple-negative breast cancer.
PMID- 28415761
TI - YAP promotes tumorigenesis and cisplatin resistance in neuroblastoma.
AB - The transcriptional co-activator Yes-associated protein (YAP) is essential for
Hippo pathway-driven tumorigenesis in various cancers. However, the expression
and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was
highly expressed in Neuroblastoma (NB) and expression levels correlated with
advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma
proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP
inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor
growth by efficiently downregulating YAP expression in tumors. Additionally, less
proliferative and more apoptotic cells were found in the Peptide 17 treatment
group. Furthermore, YAP inhibition significantly inhibited cisplatin-resistant
neuroblastoma proliferation, tumorigenesis, and invasion in vitro. The
combination of Peptide 17 with low-dose cisplatin efficiently impaired cisplatin
resistant NB subcutaneous tumor growth, being as effective as high-dose
cisplatin. Notably, the combination therapy caused lesser liver toxicity in mice
compared to the high-dose cisplatin treatment group. Collectively, this work
identifies YAP as a novel regulator of neuroblastoma proliferation,
tumorigenesis, and invasion and indicates that YAP is a potential therapeutic
target for cisplatin-resistant neuroblastoma.
PMID- 28415763
TI - Low numbers of pre-leukemic fusion genes are frequently present in umbilical cord
blood without affecting DNA damage response.
AB - Despite widely accepted notion that many childhood leukemias are likely developed
from hematopoietic stem/progenitor cells (HSPC) with pre-leukemic fusion genes
(PFG) formed in embryonic/fetal development, the data on PFG incidence in
newborns are contradictive. To provide a better understanding of a prenatal
origin of leukemia, umbilical cord blood from 500 newborns was screened for the
presence of the most frequent PFG associated with pediatric B-cell acute
lymphoblastic leukemia. This screening revealed relatively high incidence of ETV6
RUNX1, BCR-ABL1 (p190) and MLL-AF4 at very low frequencies, averaging ~14 copies
per 100,000 cells. We assume that most of these PFG might originate relatively
late in embryonic/fetal development and will be eliminated later during postnatal
development. The obtained results suggested that higher PFG copy numbers
originating in specific time windows of the hematopoietic stem cell hierarchy may
define a better prognostic tool for the assessment of leukemogenic potential. We
have observed no significant effect of low-copy PFG on radiation-induced DNA
damage response, accumulation of endogenous DNA double-stranded breaks, and
apoptosis in either lymphocytes or HSPC. Imaging flow cytometry showed lower
level of gammaH2AX foci in HSPC in comparison to lymphocytes suggesting better
protection of HSPC from DNA damage.
PMID- 28415764
TI - Inhibitor of Tec kinase, LFM-A13, decreases pro-inflammatory mediators production
in LPS-stimulated RAW264.7 macrophages via NF-kappaB pathway.
AB - Tec kinase, a prototypical member of the Tec tyrosine kinases family, was shown
to mainly govern lymphocyte proliferation. In the present study, we investigated
the role of Tec kinase in acute inflammatory response in lipopolysaccharide (LPS)
challenge. First, we demonstrate that Tec kinase activity was observed in
RAW264.7 macrophages exposed to LPS. Tec and phosphorylated Tec expression were
upregulated in a dose- and time-dependent manner after LPS stimulation. LPS
increased monocyte chemotactic protein (MCP)-1 secretion and intercellular
adhesion molecule (ICAM)-1 expression, and increasing mRNA expression was
consistently observed. LPS also induced IkappaBalpha phoshporylaytion and its
degradation, increased NF-kappaB p65 phoshporylaytion and translocation to nuclei
in RAW264.7 cells. Pretreatment with LFM-A13 decreased LPS-induced cytokines and
chemokines production and mRNA levels, blocked NF-kappaB transactivation. These
effects of LPS were also prevented by Tec-siRNA. Additionally, LFM-A13 or Tec
siRNA obviously inhibited LPS-induced TGFbeta-activated kinase 1(TAK1)
phosphorylation. Taken together, our results suggest that Tec kinase involves in
acute inflammation process in LPS-stimulated RAW264.7 cells, at least mediated by
activating TAK1/ NF-kappaB signal pathway.
PMID- 28415765
TI - Stable aneuploid tumors cells are more sensitive to TTK inhibition than
chromosomally unstable cell lines.
AB - Inhibition of the spindle assembly checkpoint kinase TTK causes chromosome mis
segregation and tumor cell death. However, high levels of TTK correlate with
chromosomal instability (CIN), which can lead to aneuploidy. We show that
treatment of tumor cells with the selective small molecule TTK inhibitor NTRC
0066-0 overrides the mitotic checkpoint, irrespective of cell line sensitivity.
In stable aneuploid cells NTRC 0066-0 induced acute CIN, whereas in cells with
high levels of pre-existing CIN there was only a small additional fraction of
cells mis-segregating their chromosomes. In proliferation assays stable aneuploid
cells were more sensitive than cell lines with pre-existing CIN. Tetraploids are
thought to be an intermediate between diploid and unstable aneuploid cells. TTK
inhibitors had the same potency on post-tetraploid and parental diploid cells,
which is remarkable because the post-tetraploids are more resistant to mitotic
drugs. Finally, we confirm that the reference compound reversine is a TTK
inhibitor and like NTRC 0066-0, inhibits the proliferation of patient-derived
colorectal cancer organoids. In contrast, treatment with TTK inhibitor did not
reduce the viability of non-proliferating T cell acute lymphoblastic leukemia
cells samples. Consequently, TTK inhibitor therapy is expected to spare non
dividing cells, and may be used to target stable aneuploid tumors.
PMID- 28415766
TI - Anti-proliferative role of recombinant lethal toxin of Bacillus anthracis on
primary mammary ductal carcinoma cells revealing its therapeutic potential.
AB - Bacillus anthracis secretes three secretary proteins; lethal factor (LF),
protective antigen (PA) and edema factor (EF). The LF has ability to check
proliferation of mammary tumors, chiefly depending on mitogen activated protein
kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of
recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on
the primary mammary ductal carcinoma cells revealed significant (p < 0.01)
reduction in proliferation of tumor cells with mean inhibition indices of 28.0 +/
1.37% and 19.6 +/- 1.47% respectively. However, treatment with rPA alone had no
significant anti-proliferative effect as evident by low mean inhibition index of
3.4 +/- 3.87%. The higher inhibition index observed for rLF alone as compared to
LeTx is contrary to the existing knowledge on LF, which explains the requirement
of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible
existence of PA independent mode of action of LF including direct receptor
mediated endocytosis or modulation of signal transduction cascade via unknown
means is hypothesized. In silico protein docking analysis of other cellular
receptors for any plausibility to play the role of receptor for LF revealed c-Met
receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96),
followed by nerve growth factor receptor (NGFR) and human epidermal growth factor
receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic
molecule against primary mammary ductal carcinoma cells and also the c-Met as
potential alternative receptor for LF to mediate and modulate PA independent
signal transduction.
PMID- 28415767
TI - Unique properties of thymic antigen-presenting cells promote epigenetic
imprinting of alloantigen-specific regulatory T cells.
AB - Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce
transplantation tolerance. However, stability of Tregs still remains contentious
and may potentially restrict their clinical use. Recent work suggested that
epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial
for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these
events are initiated already during early stages of thymic Treg development.
However, the mechanisms governing this process remain largely unknown. Here we
demonstrate that thymic antigen-presenting cells (APCs), including thymic
dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs), can induce
a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic
signature genes in developing Tregs when compared to splenic DCs (sp-DCs).
Transcriptomic profiling of APCs revealed differential expression of secreted
factors and costimulatory molecules, however neither addition of conditioned
media nor interference with costimulatory signals affected Foxp3 induction by
thymic APCs in vitro. Importantly, when tested in vivo both mTEC- and t-DC
generated alloantigen-specific Tregs displayed significantly higher efficacy in
prolonging skin allograft acceptance when compared to Tregs generated by sp-DCs.
Our results draw attention to unique properties of thymic APCs in initiating
commitment towards stable and functional Tregs, a finding that could be highly
beneficial in clinical immunotherapy.
PMID- 28415769
TI - Aurora kinase B dependent phosphorylation of 53BP1 is required for resolving
merotelic kinetochore-microtubule attachment errors during mitosis.
AB - Defects in resolving kinetochore-microtubule attachment mistakes during mitosis
is linked to chromosome instability associated with carcinogenesis as well as
resistance to cancer therapy. Here we report for the first time that tumor
suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342)
by Aurora kinase B both in vitro and in human cells, which is required for
optimal recruitment of 53BP1 at kinetochores. Furthermore, 53BP1 staining
normally localized on the outer kinetochore, extended to the whole kinetochore
when it is merotelically-attached, in concert with mitotic centromere-associated
kinesin. Kinetochore-binding of pS1342-53BP1 is essential for efficient resolving
of merotelic attachment, a spontaneous kinetochore-microtubule connection error
that usually causes aneuploidy. Consistently, loss of 53BP1 results in
significant increase in lagging chromosome events, micronuclei formation and
aneuploidy, due to the unresolved merotely in both cancer and primary cells,
which is prevented by ectopic wild type 53BP1 but not by the nonphophorylable
S1342A mutant. We thus document a novel DNA damage-independent function of 53BP1
in maintaining faithful chromosome segregation during mitosis.
PMID- 28415770
TI - Human 8-oxoguanine DNA glycosylase gene polymorphism (Ser326Cys) and cancer risk:
updated meta-analysis.
AB - Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) has been
reported to have a relationship with the risk of the development of various
cancers. Many studies have described the influence of Ser326Cys polymorphism of
the hOGG1 gene on cancer susceptibility. However, the results have remained
inconclusive and controversial. Therefore, we performed a meta-analysis to more
precisely determine the relationship between the hOGG1 polymorphism and the
development of cancer.Electronic databases including PubMed, Embase, Google
Scholar, and the Korean Studies Information Service System (KISS) were searched.
The odds ratio (OR), 95% confidence interval (CI), and p value were calculated to
assess the strength of the association with the risk of cancer using
Comprehensive Meta-analysis software (Corporation, NJ, USA). The 127 studies
including 38,757 cancer patients and 50,177 control subjects were analyzed for
the meta-analysis.Our meta-analysis revealed that G allele of Ser326Cys
polymorphism of the hOGG1 gene statistically increased the susceptibility of
cancer (all population, OR = 1.092, 95% CI = 1.051-1.134, p < 0.001; in Asian, OR
= 1.095, 95% CI = 1.048-1.145, p < 0.001; in Caucasian, OR = 1.097, 95% CI =
1.033-1.179, p = 0.002). Also, other genotype models showed significant
association with cancer (p < 0.05, respectively).The present meta-analysis
concluded that the G allele was associated with an increased risk of cancer. It
suggested that the hOGG1 polymorphism may be a candidate marker of cancer.
PMID- 28415772
TI - Endoscopic therapy for patients with pancreaticobiliary maljunction: a follow-up
study.
AB - BACKGROUND: Data on the experience of endoscopic retrograde
cholangiopancreatography (ERCP) in the management of pancreaticobiliary
maljunction (PBM) is limited. METHODS: A retrospective review of patients with
PBM who underwent therapeutic ERCP at our endoscopy center between January 2008
and January 2016 was performed. Demographic, clinical, radiological and
endoscopic data was documented. Patients who underwent sphincterotomy were
divided into dilated group and undilated group based on their common channel
diameter. RESULTS: Sixty-three PBM patients underwent 74 ERCP procedures. The
technical success rate was 97.3%. ERCP therapy significantly decreased the levels
of elevated liver enzymes and bilirubin. After an average of 27 months follow-up,
7 patients (11.1%) were lost. The overall effective rate of ERCP therapy was
60.7% (34/56). Decline in severity and frequency of abdominal pain was
significant. Procedure-related complications were observed in 5 (6.8%) cases.
Between the dilated group and undilated group, no significant difference was
observed in effective rate, adverse events and follow-up results. CONCLUSIONS:
ERCP can serve as a transitional step to stabilize PBM patients before definitive
surgery. PBM patients with undilated common channel could benefit from
sphincterotomy as well as those with dilated common channel.
PMID- 28415773
TI - Effects of CD20+ B-cell infiltration into allografts on kidney transplantation
outcomes: a systematic review and meta-analysis.
AB - The effects of CD20+ B-cell infiltration during acute rejection on graft outcomes
are controversial. The objective of this systematic review and meta-analysis was
to clarify this issue. We performed a systematic literature search for studies
published up to January 14, 2016. A total of 5 studies, with 200 patients, were
included. The presence of CD20+ B cells in renal biopsies during allograft
rejection was associated with graft loss and steroid resistance. No association
of CD20+ B-cell infiltration with C4d-positive staining of the peritubular
capillaries in renal biopsies was found in the analysis of patients who
experienced kidney graft rejection. In conclusion, CD 20+ B cell infiltration
during allograft rejection was associated with an increased risk of graft loss
and steroid resistance.
PMID- 28415774
TI - Chemoprevention of prostate cancer in men with high-grade prostatic
intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect
treatment comparison.
AB - BACKGROUND: High-grade prostatic intraepithelial neoplasia (HGPIN) is the
precursor or premalignant form of prostate cancer. At least 30% patients with a
confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy.
HGPIN patients are the appropriate at-risk population for chemoprevention
strategies investigation against prostate cancer. However the commonly used
chemoprevention agents that targeted on hormonal imbalance or lifestyle-related
factors showed varied results in HGPIN patients. METHODS: Literature searches
were conducted in PubMed, EMBASE and Cochrane library according to Cochrane
guidelines before January 31st, 2017. Direct meta-analysis were performed to
summarize the efficacy of candidate chemopreventative agents Dutasteride,
Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food
products combination. Adjusted indirect meta-analyses were employed to compare
the relative efficacy of these candidate chemoprevention agents head-to-head.
RESULTS: The overall incidence of prostate cancer in HGPIN was slightly decreased
by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P =
0.183), with minor heterogeneity (I2 = 22.3%, d???2 = 15.08, P = 0.237), but
without statistical significance. Subgroup analysis showed that green tea
catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs
23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity
(I2 = 47.9%, d???2 = 1.92, P = 0.166). The adjusted indirect meta-analysis
favored green tea catechins over other chemoprevention agents, and significantly
when compared to natural food products combination (RR = 0.355, 95% CI: 0.134
0.934). CONCLUSION: The overall efficacy of chemoprevention agents in HGPIN
patients is limited. But Green tea catechins showed the superiority to decrease
prostate cancer in HGPIN patients.
PMID- 28415775
TI - Adverse genomic alterations and stemness features are induced by field
cancerization in the microenvironment of hepatocellular carcinomas.
AB - Hepatocellular Carcinoma (HCC) commonly develops in chronically damaged liver
tissues. The resulting regenerative and inflammatory processes create an adverse
milieu that promotes tumor-initiation and progression. A better understanding of
the hepatic tumor-microenvironment interaction might infer profound therapeutic
implications.Integrative whole genome and transcriptome analyses of different
tumor regions, the invasive tumor border and tumor-surrounding liver (SL) were
performed to identify associated molecular alterations and integrated with our
existing HCC database. Expression levels and localization of established CSC
markers were assessed in pre-neoplastic lesions and confirmed in two independent
patient cohorts using qRT-PCR, immunohistochemistry and immunofluorescence.Our
results indicate that genomic and transcriptomic profiles between SL and
different tumor regions are quite distinct. Progressive increase in genetic
alterations and activation of pathways related to proliferation as well as
apoptosis were observed in the tumor tissue, while activation of stemness markers
was present in cirrhotic SL and continuously decreased from pre-neoplastic
lesions to HCC. Interestingly, the invasive tumor border was characterized by
inflammatory and EMT-related gene sets as well as activation of pro-survival
signaling. Consistently, integration of gene expression signatures with two
independent HCC databases containing 300 HCCs revealed that border signatures are
predictive of HCC patient survival.Prognostic significance of the permissive
liver microenvironment might be a consequence of a pro-oncogenic field effect
that is caused by chronic regenerative processes. Activation of key oncogenic
features and immune-response signaling indicates that the cross-talk between
tumor and microenvironment might be a promising therapeutic and/or preventive
target.
PMID- 28415776
TI - Targeting protein homeostasis with nelfinavir/salinomycin dual therapy
effectively induces death of mTORC1 hyperactive cells.
AB - Uncontrolled cell growth in Tuberous Sclerosis Complex occurs due to
inappropriate activation of mechanistic (mammalian) target of rapamycin complex 1
(mTORC1). The current therapy, rapamycin, produced promising clinical trial
results, but patient tumours regrow if treatment is discontinued, revealing
rapamycin has cytostatic properties rather than a cytotoxic effect. Taking
advantage of the enhanced levels of endoplasmic reticulum (ER) stress present in
TSC2-null cells, we investigated drug combinations producing a cytotoxic
response. We found a nelfinavir and salinomycin combination specifically killed
TSC2-deficient, mTORC1 hyperactive cells. Cytotoxicity was rescued by reducing
protein synthesis, either through mTORC1 inhibition or cycloheximide treatment.
This indicates that the drug combination targets the cells by tipping the protein
homeostasis balance of the already metabolically stressed TSC2-deficient cells in
favour of cell death. Furthermore, this drug combination also inhibited tumour
formation in TSC2-deficient cell models and caused tumour spheroid death in 3D
culture. Importantly, the 3D assay could differentiate the cytostatic agent,
rapamycin, from the cytotoxic nelfinavir/salinomycin combination. Sporadic cancer
cell lines with hyperactive mTORC1 signalling were also susceptible to this
nelfinavir/salinomycin drug combination. This work indicates that the protein
homeostasis pathway is an attractive therapeutic target in both Tuberous
Sclerosis Complex and mTORC1-driven sporadic cancers.
PMID- 28415779
TI - Relationship of p73 gene polymorphism and additional gene-smoking and gene
obesity interaction with non-small cell lung cancer risk.
AB - AIM: The aim of this study was to investigate the impact of G4C14-to-A4T14
polymorphism within P73 gene and additional interactions with current smoking and
obesity on non-small cell lung cancer (NSCLC) risk in a Chinese population.
RESULTS: Logistic regression analysis showed a significant association between
genotypes of the AT allele in G4C14-to-A4T14 and decreased NSCLC risk. NSCLC risk
was significantly lower in carriers of the G4C14-to-A4T14- AT allele than those
with GC/GC genotype (AT/AT + GC/AT versus GC/GC), adjusted OR (95%CI) = 0.68
(0.55-0.93). We also found that the OR (95%CI) was 1.88 (1.32-2.47) for current
smokers compared with never smokers and 0.69 (0.40-0.95) for obese subjects
compared to participants with normal BMI. Never smokers with AT/AT or GC/AT of
the G4C14-to-A4T14 genotype have the lowest NSCLC risk compared with smokers with
the GC/GC genotype after covariates adjustment, OR (95%CI) = 0.52 (0.26-0.87).
Obese participants with G4C14-to-A4T14- AT/AT or GC/AT genotype have the lowest
NSCLC risk compared with non- obese subjects with the GC/GC genotype after
adjusting for covariates, OR (95% CI) = 0.56 (0.33-0.85). MATERIALS AND METHODS:
A logistic regression model was used to examine the association between G4C14-to
A4T14 polymorphism and NSCLC, and its interaction with current smoking and
obesity. The odds ratios (OR) and 95% confident intervals (95%CI) were
calculated. CONCLUSIONS: Our results support an important association between the
G4C14-to-A4T14 and decreased NSCLC risk and additional impact of an interaction
between G4C14-to-A4T14 and smoking or obesity on NSCLC risk.
PMID- 28415780
TI - Long noncoding RNA PCAT-14 induces proliferation and invasion by hepatocellular
carcinoma cells by inducing methylation of miR-372.
AB - Long non-coding RNAs (lncRNAs) regulate oncogenesis by inducing methylation of
CpG islands to silence target genes. Here we show that the lncRNA PCAT-14 is
overexpressed in patients with hepatocellular carcinoma (HCC), and is associated
with a poor prognosis after surgery. Our results demonstrate that PCAT-14
promotes proliferation, invasion, and cell cycle arrest in HCC cells. In
addition, PCAT-14 inhibits miR-372 expression by inducing methylation of the miR
372 promoter. Simultaneously, miR-372 eliminates the effects of PCAT-14 on
proliferation, invasion, and cell cycle in HCC cells. Moreover, PCAT-14 regulates
expression of ATAD2 and activation of the Hedgehog pathway via miR-372. These
findings indicate that PCAT-14 plays an important role in HCC, and may serve as a
novel prognostic factor and therapeutic target.
PMID- 28415781
TI - Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype.
AB - Variations in DNA repair genes have been reported as key factors in gastric
cancer (GC) susceptibility but results among studies are inconsistent. We aimed
to assess the relevance of DNA repair gene polymorphisms and environmental
factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA
from 603 patients with primary GC and 603 healthy controls was typed for 123
single nucleotide polymorphisms in DNA repair genes using the Illumina platform.
Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95%
confidence interval (CI): 1.55-2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22
2.57), and family history of GC (OR: 2.87; 95% CI: 1.85-4.45) were identified as
independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95%
CI: 0.56-0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56-0.96), and BRIP1
rs4986764T (OR: 0.55; 95% CI: 0.38-0.78) variants were associated with lower GC
risk. Significant associations with specific anatomopathological GC subtypes were
also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G,
and rs3136038T variants being inversely associated with cardia GC risk. Moreover,
the XRCC3 rs861528 allele A was significantly increased in the patient subgroup
with diffuse GC (OR: 1.75; 95% CI: 1.30-2.37). Our data show that specific TP53,
BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk
and specific subtypes in Caucasians.
PMID- 28415782
TI - Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple
myeloma cells.
AB - Curative responses in the treatment of multiple myeloma (MM) are limited by the
emergence of therapeutic resistance. To address this problem, we set out to
identify druggable mechanisms that convey resistance to proteasome inhibitors
(PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In
isogenic pairs of PI sensitive and resistant cells, we observed stark differences
in cellular bioenergetics between the divergent phenotypes. PI resistant cells
exhibited increased mitochondrial respiration driven by glutamine as the
principle fuel source. To target glutamine-induced respiration in PI resistant
cells, we utilized the glutaminase-1 inhibitor, CB-839. CB-839 inhibited
mitochondrial respiration and was more cytotoxic in PI resistant cells as a
single agent. Furthermore, we found that CB-839 synergistically enhanced the
activity of multiple PIs with the most dramatic synergy being observed with
carfilzomib (Crflz), which was confirmed in a panel of genetically diverse PI
sensitive and resistant MM cells. Mechanistically, CB-839 enhanced Crflz-induced
ER stress and apoptosis, characterized by a robust induction of ATF4 and CHOP and
the activation of caspases. Our findings suggest that the acquisition of PI
resistance involves adaptations in cellular bioenergetics, supporting the
combination of CB-839 with Crflz for the treatment of refractory MM.
PMID- 28415783
TI - Mass spectral analysis of the multikinase inhibitor BZG and its metabolites and
analysis of their binding to vascular endothelial growth factor receptor-2.
AB - We previously showed that BZG is a novel multitarget kinase inhibitor, which
inhibited hepatocellular carcinoma in vivo and in vitro. In the present study, we
used ultra-performance liquid chromatography coupled with quadrupole time-of
flight mass spectrometry (UPLC/Q-TOF MS) to characterize BZG and its metabolites
generated in vivo. The probable metabolic mechanism was further confirmed by
analysis of Phase I and Phase II metabolism in liver microsomes and with
recombinant enzymes. In addition, the binding affinities of BZG metabolites to
vascular endothelial growth factor receptor 2 (VEGFR2) were predicted using
electronic high throughput screening (eHiTS). The results showed that BZG
underwent phase I and phase II metabolism. We detected 11 BZG metabolites and
identified hydroxylation, glucuronation, acetylation, sulfonation and degradation
as the major metabolic processes in vivo and in vitro. Five of the eleven
metabolites showed highly favorable eHiTS energy scores that were lower than
sorafenib. Knowledge of the in vivo metabolic pathways of BZG and its binding
affinities to VEGFR2 will be beneficial for further clinical development of BZG.
PMID- 28415784
TI - Misregulation of DNA damage repair pathways in HPV-positive head and neck
squamous cell carcinoma contributes to cellular radiosensitivity.
AB - Patients with human papillomavirus type 16 (HPV)-associated oropharyngeal
squamous cell carcinomas (OPSCC) display increased sensitivity to radiotherapy
and improved survival rates in comparison to HPV-negative forms of the disease.
However the cellular mechanisms responsible for this characteristic difference
are unclear. Here, we have investigated the contribution of DNA damage repair
pathways to the in vitro radiosensitivity of OPSCC cell lines. We demonstrate
that two HPV-positive OPSCC cells are indeed more radiosensitive than two HPV
negative OPSCC cells, which correlates with reduced efficiency for the repair of
ionising radiation (IR)-induced DNA double strand breaks (DSB). Interestingly, we
show that HPV-positive OPSCC cells consequently have upregulated levels of the
proteins XRCC1, DNA polymerase beta, PNKP and PARP-1 which are involved in base
excision repair (BER) and single strand break (SSB) repair. This translates to an
increased capacity and efficiency for the repair of DNA base damage and SSBs in
these cells. In addition, we demonstrate that HPV-positive but interestingly more
so HPV-negative OPSCC display increased radiosensitivity in combination with the
PARP inhibitor olaparib. This suggests that PARP inhibition in combination with
radiotherapy may be an effective treatment for both forms of OPSCC, particularly
for HPV-negative OPSCC which is relatively radioresistant.
PMID- 28415785
TI - The role of nitric oxide pathway in arginine transport and growth of IPEC-1
cells.
AB - L-Arginine itself and its metabolite-nitric oxide play great roles in intestinal
physiology. However, the molecular mechanism underlying nitric oxide pathway
regulating L-Arginine transport and cell growth is not yet fully understood. We
report that inhibition of nitric oxide synthase (NOS) significantly induced cell
apoptosis (p < 0.05), and promoted the rate of Arginine uptake and the
expressions of protein for CAT-2 and y+LAT-1 (p < 0.05), while reduced protein
expression of CAT-1. And NOS inhibition markedly decreased the activation of
mammalian target of rapamycin (mTOR) and PI3K-Akt pathways by Arginine in the
IPEC-1 cells (p < 0.05). Taken together, these data suggest that inhibition of NO
pathway by L-NAME induces a negative feedback increasing of Arginine uptake and
CAT-2 and y+LAT-1 protein expression, but promotes cell apoptosis which involved
inhibiting the activation of mTOR and PI3K-Akt pathways.
PMID- 28415786
TI - Arterial stiffness and blood pressure improvement in aldosterone-producing
adenoma harboring KCNJ5 mutations after adrenalectomy.
AB - The aim of this study was to show the effect of KCNJ5 mutational status on
arterial stiffness in aldosterone-producing adenomas after adrenalectomy. Between
February 2008 and January 2010, we prospectively enrolled 108 aldosterone
producing adenoma patients undergoing adrenalectomy. We conducted repeated
measurements of pulse wave velocity at baseline, 6 months, and 12 months after
adrenalectomy, grouped by KCNJ5 mutational status. Prognostic factors of arterial
stiffness and risk for hypertension at 12 months after adrenalectomy were
analyzed after propensity score matching in a 1:1 ratio. After matching for age,
sex and body mass index, 88 patients were divided equally into KCNJ5-mutant and
non-mutant groups. KCNJ5 mutational status was not an independent variable in
either the generalized estimating equation model (p = 0.147) or the percentage
change of brachial-ankle pulse wave velocity (p = 0.106). The generalized
additive model smoothing plot showed that aldosterone-producing adenoma patients
who carried the KCNJ5 mutation and were aged between 37 and 60 may have a
hypertension recovery advantage. According to our observations during a 12-month
follow-up after adrenalectomy, KCNJ5 mutational status was not associated with
improvement in arterial stiffness.
PMID- 28415787
TI - Knockdown of P4HA1 inhibits neovascularization via targeting glioma stem cell
endothelial cell transdifferentiation and disrupting vascular basement membrane.
AB - Emerging evidence has demonstrated transdifferentiation process of glioma stem
cells (GSCs) into endothelial cells (ECs) in glioma neovascularization. Herein,
we focused on screening for genes that were differentially expressed in the
transdifferentiation process using microarray analysis. Bioinformatics analysis
revealed differential expression of the prolyl 4-hydroxylase subunit alpha-1
(P4HA1) gene. We determined that P4HA1 expression was correlated with
histological grade, the level of Ki67 and microvessel density (MVD) in human
glioma specimens. Knockdown of P4HA1 inhibited the proliferation, migration and
tube formation of GSCs in vitro. In vivo studies revealed that the downregulation
of P4HA1 inhibited intracranial tumor growth, prolonged the overall survival time
of xenograft mice and suppressed the neovascularization in brain tumors.
Moreover, P4HA1 regulates the expression of vascular endothelial growth factor A
(VEGF-A), especially an anti-angiogenic isoform-VEGF165b. Additionally, knockdown
of P4HA1 inhibited the synthesis of collagen IV, and hence disrupted the
structures of vascular basement membranes (BMs) in gliomas. Our study indicates
that P4HA1 plays a pivotal role in the process of GSC-EC transdifferentiation and
the structural formation of vascular BMs.
PMID- 28415788
TI - Inhibitory effects of BMP9 on breast cancer cells by regulating their interaction
with pre-adipocytes/adipocytes.
AB - Bone morphogenetic protein 9 (BMP9) possesses multiple functions, but its effects
on breast cancer cells in adipose microenvironment are still unclear. This study
aimed to investigate whether BMP9 is able to modulate the interaction between pre
adipocytes/adipocytes and breast cancer cells. An in vitro co-culture system was
established by using pre-adipocytes/adipocytes and MDA-MB-231 breast cancer cells
with BMP9 over-expression. The leptin expression and leptin-induced signaling
pathway were evaluated in this co-culture system. MTT assay, EdU assay and flow
cytometry were used to assess the proliferation of MDA-MB-231 cells. Wound
healing assay and Transwell migration assay were used to assess the migration of
MDA-MB-231 cells. Immunofluorescence staining was used to detect the expression
of leptin recepter (ObR) in MDA-MB-231 cells. The expression of key molecules in
leptin signaling pathway in co-culture system were detected by Western blotting.
MDA-MB-231 cells and pre-adipocytes/adipocytes were inoculated into nude mice,
the tumor volume was measured, and the protein expression of key molecules in
leptin signaling pathway was detected. Results showed BMP9 inhibited breast tumor
growth in vitro and in vivo and reduced the migration of breast cancer cells in
vitro. MDA-MB-231 cells with BMP9 over-expression decreased leptin expression in
pre-adipocytes/adipocytes and had reduced phosphorylation of STAT3, ERK1/2 and
AKT. Taken together, our study indicates that BMP9 can inhibit the growth and
metastasis of breast cancer cells, which may be related to interaction between
pre-adipocytes/adipocytes and MDA-MB-231 cells via leptin signaling pathway.
PMID- 28415789
TI - Hmga2 translocation induced in skin tumorigenesis.
AB - Hmga2 protein, a transcription factor involved in chromatin architecture, is
expressed chiefly during development, where it has many key biological functions.
When expressed in adult tissues from in various organs, Hmga2 is always related
to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not
yet understood. We demonstrated that Hmga2 can be found in non-transformed
epidermis, specifically located to the membrane of keratinocytes (KCs) in
epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and
TPA mouse models was associated with translocation of the Hmga2 protein from the
membrane into the nucleus, where Hmga2 induced its own expression by binding to
the Hmga2 promoter. Panobinostat, an HDAC inhibitor, downregulated Hmga2
expression by preventing Hmga2 to bind its own promoter, and thus inhibiting
Hmga2 promoter activity. Hmga2 translocation to the nucleus could in part be
prevented by an inhibitor for ROCK1. Our findings demonstrate that upon program
of benign papilloma to malignant cSCC of skin tumorigenesis, Hmga2 translocates
in a ROCK-dependent manner from the membrane to the nucleus, where it serves as
an autoregulatory transcription factor, causing cell transformation.
PMID- 28415790
TI - Hyperglycemia via activation of thromboxane A2 receptor impairs the integrity and
function of blood-brain barrier in microvascular endothelial cells.
AB - Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases,
including stroke, atherosclerosis and hypertension. This study was conducted to
elucidate whether and how thromboxane receptor (TPr) activation contributes to
blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular
endothelial cells (HBMECs) were cultured. The levels of phosphorylated
endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p
Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG)
or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt.
These effects were abolished by pharmacological or genetic inhibitors of TPr.
HG/U46619-induced suppressions of eNOS and Akt phosphorylation were accompanied
by upregulation of PTEN and Ser380/Thr382/383 PTEN phosphorylation. PTEN-specific
siRNA restored Akt-eNOS signaling in the face of TPr activation or HG. The small
GTPase, Rho, was also activated by HG stimulation, and pretreatment of HBMECs
with Y27632, a Rho-associated kinase (ROCK) inhibitor, rescued HG-impaired Akt
eNOS signaling. In STZ-injected rats, we found that hyperglycemia dramatically
increased the levels of PTEN and PTEN-Ser380/Thr382/383 phosphorylation, reduced
both levels of p-eNOS and p-Akt, and disrupted BBB function assayed by Evans blue
staining, which were abolished by SQ29548 treatment. We conclude that
hyperglycemia activates thromboxane A2 receptor to impair the integrity and
function of blood-brain barrier via the ROCK-PTEN-Akt-eNOS pathway.
PMID- 28415791
TI - Evaluation of the circulating level of fibroblast activation protein alpha for
diagnosis of esophageal squamous cell carcinoma.
AB - To evaluate whether circulating fibroblast activation protein alpha (FAPalpha)
could serve as a biomarker for the diagnosis of esophageal squamous cell
carcinoma (ESCC), enzyme-linked immunosorbent assay (ELISA) was used to detect
plasma FAPalpha in 556 participants including ESCC group, benign esophageal
disease group, healthy controls and other cancer controls group. The levels of
plasma FAPalpha were significantly decreased in ESCC patients (P < 0.001) and
showed a positive correlation with HDL-C levels (R = 0.372, P < 0.001). The
sensitivity and specificity of plasma FAPalpha were 56.1% and 85.6% based on the
optimal cut-off (49.04 ng/ml, AUC = 0.714). The combination of FAPalpha and the
traditional biomarkers (CEA, CYFR211 and SCCA) improved the sensitivity (41.5%)
without compromising the specificity (95.0%). Contradictorily, the
immunohistochemical staining revealed the overexpression of FAPalpha in stroma of
ESCC tissues. So the source of soluble FAPalpha was further explored by qRT-PCR,
Western blotting, ELISA and immunoprecipitation in fibroblast cell lines and
mouse xenograft models. We found that the plasma FAPalpha was not correlated with
the FAPalpha expressed in tumor, and the multi-organ might contribute to the
circulating levels of FAPalpha including skeletal muscle, liver and bone marrow.
These results indicated that the low plasma FAPalpha level might due to the
systemic reaction to the presence of tumor and circulating FAPalpha level might
be a potential indicator for diagnosing ESCC.
PMID- 28415792
TI - A CD44-specific peptide, RP-1, exhibits capacities of assisting diagnosis and
predicting prognosis of gastric cancer.
AB - Early diagnosis and evaluation of prognosis are both crucial for preventing poor
prognosis of patients with gastric cancer (GC), a leading cause of cancer-related
deaths worldwide. Cluster of differentiation 44 (CD44), an indicator of cancer
stem cells, can be specifically targeted by molecular probes and detected in
tissues of GC in a large quantity. In current study we found that RP-1, a
specific peptide binding to CD44 protein, exhibited the potentials of specific
binding to CD44 high-expressing cancer cells both in vitro and in vivo, and the
capacity of predicting prognosis of human GC in a microarray assay. Results
showed that RP-1 was characterized by high affinity, sensitivity and specificity,
and low toxicity, suggesting RP-1 could be an ideal bio-probe for accessory
diagnosis of GC. Further immunohistochemical studies and statistical analysis of
tissue microarray of human GC demonstrated similar sensitivity and specificity of
RP-1 with the monoclonal anti-CD44 antibody in the diagnosis of GC, and even
proved that positive RP-1 could be an independent risk factor. Therefore, this
study suggests RP-1 has the potentials of binding to CD44 protein expressed on
the membrane of GC cells, and demonstrates the feasibility and reliability of its
further application in molecular diagnosis and prognostic prediction of GC.
PMID- 28415793
TI - Clinical framework for next generation sequencing based analysis of treatment
predictive mutations and multiplexed gene fusion detection in non-small cell lung
cancer.
AB - Precision medicine requires accurate multi-gene clinical diagnostics. We describe
the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic
framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1
gene fusion assay for combined analysis of treatment predictive alterations in
non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden
(Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot
mutation concordance), after which 533 consecutive NSCLCs were collected during
one-year of routine clinical analysis in the healthcare region (~90% advanced
stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the
533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected
variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135
successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH
fusion positive case was missed by the NanoString assay. Stratification of the
533-sample cohort based on actionable alterations in 11 oncogenes revealed that
66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not
otherwise specified harbored >=1 alteration. In adenocarcinoma, 10.6% of patients
(50.3% if including KRAS) could potentially be eligible for emerging
therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or
ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1%
with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are
feasible in NSCLC for clinical diagnostics, identifying notable proportions of
patients potentially eligible for emerging molecular therapeutics.
PMID- 28415794
TI - MicroRNAs of the mir-17~92 cluster regulate multiple aspects of pancreatic tumor
development and progression.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by
resistance to currently employed chemotherapeutic approaches. Members of the mir
17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise
roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse
models, we show that loss of mir-17~92 reduces ERK pathway activation downstream
of mutant KRAS and promotes the regression of KRASG12D-driven precursor
pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal
exocrine tissue. In a PDAC model driven by concomitant KRASG12D expression and
Trp53 heterozygosity, mir-17~92 deficiency extended the survival of mice that
lacked distant metastasis. Moreover, mir-17~92-deficient PDAC cell lines display
reduced invasion activity in transwell assays, form fewer invadopodia rosettes
than mir-17~92-competent cell lines and are less able to degrade extracellular
matrix. Specific inhibition of miR-19 family miRNAs with antagomirs recapitulates
these phenotypes, suggesting that miR-19 family miRNAs are important mediators of
PDAC cell invasion. Together these data demonstrate an oncogenic role for mir
17~92 at multiple stages of pancreatic tumorigenesis and progression;
specifically, they link this miRNA cluster to ERK pathway activation and
precursor lesion maintenance in vivo and identify a novel role for miR-19 family
miRNAs in promoting cancer cell invasion.
PMID- 28415795
TI - Renal sympathetic denervation guided by renal nerve stimulation to treat
ventricular arrhythmia in CKD patients with ICD.
AB - Chronic kidney disease (CKD) patients on stage 4 present greater risk rates for
malignant ventricular arrhythmia events. This study examined patients with CKD in
stages 1, 2, 3 and 4, left ventricular dysfunction and automatic implantable
cardioverter-defibrillator (ICD). Our goal was to record the appropriate
therapies, "Anti-tachycardia Therapy Pacing" (ATP) and shock events during the 18
months of follow-up and compare the incidence and severity of these at different
stages of CKD, mainly in patients with CKD stage 4 underwent renal sympathetic
denervation (RSD) guided by renal nerve stimulation (RNS). One hundred and
fifteen patients were evaluated once every three months till 18 months of follow
up. The arrhythmic events were assessed at each follow-up visit. Comparing the
groups, we can see the number of ATP and shock events recorded by ICD during 18
months of follow-up, and differences in the number of therapeutic events between
the various stages of CKD. The hazard ratio (HR), 95% confidence interval (CI)
and P value for ATP and shock events between all the CKD stages were evaluated by
the log-rank/Mantel-Haenszel test. At the 18th month of follow-up, 75% of
patients with CKD stage 4 received ATP, and 70% were treated with shock while
only 20% of the subjects with CKD stage 4 that were submitted to RSD received ATP
and 20% were treated with shock, P<0.0001 and P=0.0002, respectively. In our
study, a decline occurred in the incidence of arrhythmias, and therefore,
appropriate ICD therapies in advanced stages of CKD, reducing the risk rates for
these events in patients with CKD on stage 4 after RSD guided by RNS in
comparison to the other CKD stages. Our results suggest that RSD can control the
higher incidence of malignant arrhythmias in advanced CKD stages.
PMID- 28415796
TI - Macrophage-stimulated microRNA expression in mural cells promotes transplantation
induced neointima formation.
AB - In this study, we tested the possibility that macrophages might contribute to
neointima formation by stimulating microRNA expressions in mural cells. Thoracic
aortas from F344 rats were transplanted into recipient Lewis rats. Clodronate
liposome was used for in vivo macrophage depletion. Using miR-21 as a prototypic
example of vascular enriched microRNA, we showed that macrophage depletion
reduced the expression level of miR-21, which was upregulated in the allograft.
This effect of macrophage depletion was accompanied by attenuations in neointimal
hyperplasia and transplantation-induced vascular inflammation. Using in vitro
assays, we identified that macrophages might stimulate miR-21 expression in
smooth muscle cells and adventitial fibroblasts via the release of tumor necrosis
factor-alpha. We also showed that silencing of miR-21 suppressed tumor necrosis
factor-induced proliferation, migration, and inflammatory responses in mural
cells. Our results suggest that macrophage may promote transplantation-induced
neointima formation by stimulating miR-21 expression in vascular mural cells,
which promotes mural cell proliferation, migration and/or inflammation. Moreover,
we have established that tumor necrosis factor-alpha has a major role in
mediating this paracrine process.
PMID- 28415797
TI - Rab7 GTPase controls lipid metabolic signaling in myeloid-derived suppressor
cells.
AB - Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that
regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs)
through over-activation of mammalian target of rapamycin (mTOR). Affymetrix
GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed
upregulation of Rab7 GTPase protein, which belongs to a superfamily of small
molecular-weight GTPase known to regulate intracellular membrane trafficking from
early to late endosomes and lysosomes. Here, the physical protein-protein
interaction between Rab7 GTPase and mTOR has been detected by co
immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like
HD1B myeloid cell lines. The GST pull down assay using the recombinant GST-Rab7
GTPase fusion protein showed that Rab7 GTPase interacts with the mTOR N-terminal
heat repeat domain. Rab7 GTPase siRNA knocking down reversed the altered
lysosome/mTOR distribution and expression levels in HD1B cells. Rab7 GTPase siRNA
knocking down in isolated bone marrow lal-/- MDSCs or HD1B cells not only reduced
over-activation of mTOR and its downstream effector S6, but also decreased
glucose consumption, decreased ROS over-production, and increased healthy
mitochondria by membrane potential measurement. Inhibition of Rab7 GTPase led to
reduced lal-/- MDSCs differentiation from bone marrow Lin- progenitor cells,
reduced lal-/- MDSCs trans-endothelial migration, and reversed lal-/- MDSCs
suppression of T cell proliferation. Furthermore, inhibition of Rab7 GTPase
reduced lal-/- MDSCs ability to stimulate tumor cell proliferation in vitro,
tumor growth in vivo, and tumor invasion. Together, these results showed that
Rab7 GTPase is critically involved in MDSCs homeostasis and pathogenic functions.
PMID- 28415798
TI - Tumor-derived IL-18 induces PD-1 expression on immunosuppressive NK cells in
triple-negative breast cancer.
AB - PURPOSE: While the inflammatory cytokine interleukin-18 (IL-18) is known to
activate natural killer (NK) cells, its precise role in cancer is controversial.
In this study, we investigated the role of tumor-derived IL-18 on peripheral
blood NK cells in breast cancer patients. RESULTS: In breast cancer cell lines,
IL-18 was expressed and secreted in the triple-negative breast cancer (TNBC) cell
lines MDA-MB-231 and HCC-70 but not in MCF-7 cells. The immature and non
cytotoxic CD56dimCD16dim/- NK cell fraction was increased following co-culture
with MDA-MB-231 cells, and this increase was not observed with tumor cells
transfected with siRNA for IL-18 or in MCF-7 cells. In addition, tumor-derived IL
18 increased PD-1 expression on CD56dimCD16dim/- NK cells, although no effect on
PD-L1 expression in tumor cells was observed. Among EBC patients, serum IL-18
levels were significantly increased in those with a TNBC subtype compared to
levels from patients with other subtypes, and the IL-18 levels were strongly
associated with poor survival. Similarly, serum IL-18 and CD56dimCD16dim/- NK
cells were also increased in patients with metastatic TNBC who had progressive
disease following cytotoxic chemotherapy. EXPERIMENTAL DESIGN: We performed in
vitro experiments in breast cancer cell lines, measured cytokine levels by RT
qPCR, western blot, and ELISA, and analyzed NK cell subsets by flow cytometry.
For clinical validation, we collected and analyzed blood sample from patients
with early breast cancer (EBC, N = 545) and metastatic breast cancer (MBC, N =
42). CONCLUSIONS: Our data revealed that tumor-derived IL-18 is associated with
bad prognosis in patients with TNBC. Tumor-derived IL-18 increased the
immunosuppressive CD56dimCD16dim/- NK cell fraction and induced PD-1 expression
on these NK cells.
PMID- 28415799
TI - The pancreas responds to remote damage and systemic stress by secretion of the
pancreatic secretory proteins PSP/regI and PAP/regIII.
AB - INTRODUCTION: In patients with infection and sepsis serum levels of Pancreatic
Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP
during these conditions is presumably the pancreas, however, an intestinal origin
cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was
identified in the pancreas. These proteins were also localized in intestinal
organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal
models of sepsis and in healthy humans. RESULTS: PSP and PAP responded to remote
lesions in rats although the pancreatic response was much more pronounced than
the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content
in the pancreas compared to any other organ while PAP was most abundant in the
small intestine. Both proteins responded to CLP or sham operation in the
pancreas. PSP also increased in the intestine during CLP. The distribution of PSP
and PAP in human tissue mirrored the distribution in the murine models. MATERIALS
AND METHODS: Distribution of PSP and PAP was visualized by immunohistochemistry.
Rats and mice underwent midline laparotomies followed by mobilization of tissue
and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture
(CLP) procedures or sham laparotomies were performed. Human tissue extracts were
analyzed for PSP and PAP. CONCLUSIONS: The pancreas reacts to remote lesions and
septic insults in mice and rats with increased PSP synthesis, while PAP is
selectively responsive to septic events. Furthermore, our results suggest that
serum PSP in septic patients is predominantly derived through an acute phase
response of the pancreas.
PMID- 28415800
TI - Selenophosphate synthetase 1 (SPS1) is required for the development and selenium
homeostasis of central nervous system in chicken (Gallus gallus).
AB - Selenophosphate synthetase (SPS) is essential for selenoprotein biosynthesis. In
two SPS paralogues, SPS1 was only cloned from a cDNA library prepared from avian
organ. However, the biological function of SPS1 in chicken central nervous system
(CNS) remains largely unclear. To investigate the role of avian SPS1 in the
development and selenium (Se) homeostasis of CNS, fertile eggs, chicken embryos,
embryo neurons and chicks were employed in this study. The response of SPS1
transcription to the development and Se levels of CNS tissues was analyzed using
qRT-PCR. SPS1 gene exists extensively in the development of chicken CNS. The wide
expression of avian SPS1 can be controlled by the Se content levels, which
suggests that SPS1 is important in the regulation of Se homeostasis. The
fundamental mechanism of these effects is that Se alters the half-life and
stability of SPS1 mRNA. Therefore, SPS1 exerts an irreplaceable biological
function in chicken CNS and Se homeostasis is closely related to the expression
of SPS1. These results suggested that SPS1 was required for the development and
Se homeostasis of CNS in chicken.
PMID- 28415801
TI - Identification of long non-coding RNAs that stimulate cell survival in bladder
cancer.
AB - For many years, research on the biology underlying bladder cancer focused on
protein-coding genes which cover only about 3% of the human genome. Recently, it
was discovered that a large part of the human genome is actively transcribed as
long non-coding RNAs (lncRNAs). LncRNAs are master regulators of gene expression
and several lncRNAs were shown to play a role in bladder cancer development and
progression. Here, we analyzed lncRNA expression in muscle-invasive bladder
cancer (MIBC) using the MiTranscriptome database of cancer lncRNA expression
profiles, and we studied their function in bladder cancer-derived tumor cells.
Analysis of the MiTranscriptome lncRNA expression data revealed four MIBC
subgroups, which partially overlapped with the four mRNA clusters identified by
The Cancer Genome Atlas consortium. Up-regulation of three lncRNAs CAT266,
CAT1297, and CAT1647 in bladder cancer, in comparison to normal urothelium, was
confirmed in an independent series of normal, non-muscle invasive (NMIBC) and
MIBC tissue samples. Furthermore, expression levels of CAT1297 were found to be
correlated with disease-free and overall survival in MIBC. Knockdown of CAT266,
CAT1297, and CAT1647 decreased cell viability and colony formation, due to the
induction of apoptosis. In conclusion, our data show that lncRNAs expression is
de-regulated in MIBC and three aberrantly expressed transcripts regulate
proliferation and apoptosis. Our data indicate that lncRNAs play an important
role in MIBC development and progression and are a treasure chest for the
discovery of new biomarkers.
PMID- 28415806
TI - Lithium protects hippocampal progenitors, cognitive performance and hypothalamus
pituitary function after irradiation to the juvenile rat brain.
AB - Cranial radiotherapy in children typically causes delayed and progressive
cognitive dysfunction and there is no effective preventive strategy for radiation
induced cognitive impairments. Here we show that lithium treatment reduced
irradiation-induced progenitor cell death in the subgranular zone of the
hippocampus, and subsequently ameliorated irradiation-reduced neurogenesis and
astrogenesis in the juvenile rat brain. Irradiation-induced memory impairment,
motor hyperactivity and anxiety-like behaviour were normalized by lithium
treatment. Late-onset irradiation-induced hypopituitarism was prevented by
lithium treatment. Additionally, lithium appeared relatively toxic to multiple
cultured tumour cell lines, and did not improve viability of radiated DAOY cells
in vitro. In summary, our findings demonstrate that lithium can be safely
administered to prevent both short- and long-term injury to the juvenile brain
caused by ionizing radiation.
PMID- 28415808
TI - IKK inhibition by BMS-345541 suppresses breast tumorigenesis and metastases by
targeting GD2+ cancer stem cells.
AB - We have identified that the ganglioside GD2 is a marker for breast cancer stem
cells (BCSCs), and that targeting the enzyme GD3 synthase (GD3S, which regulates
GD2 biosynthesis) reduces breast tumorigenesis. The pathways regulating GD2
expression, and their anomalous functions in BCSC, are unclear. Proteomic
analysis of GD2+ and GD2- cells from breast cancer cell lines revealed the
activation of NFkappaB signaling in GD2+ cells. Dose- and time-dependent
suppression of NFkappaB signaling by the small molecule inhibitor BMS-345541
reduced GD2+ cells by > 90%. Likewise, BMS-345541 inhibited BCSC GD3S expression,
mammosphere formation, and cell migration/invasion in vitro. Breast tumor-bearing
mice treated with BMS-345541 showed a statistically significant decrease in tumor
volume and exhibited prolonged survival compared to control mice, with a median
survival of 78 d for the BMS-345541-treated group vs. 58 d for the controls.
Moreover, in an experimental metastases model, treatment with BMS-345541 reduced
the lung metastases by > 5-fold. These data suggest that GD2 expression and
function,and NFkappaB signaling, are related, and they control BCSCs tumorigenic
characteristics. Thus, the suppression of NFkappaB signaling by BMS-345541 is a
potentially important advance in controlling breast cancer growth and metastases.
PMID- 28415805
TI - Regulatory functional territory of PLK-1 and their substrates beyond mitosis.
AB - Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and
is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly
associated with poor prognosis and cancer progression, it is one of the most
extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell
cycle events, such as spindle pole maturation, chromosome segregation and
cytokinesis. However, studies have demonstrated that the role of PLK-1 is not
only restricted to mitosis, but PLK-1 can also regulate other vital events beyond
mitosis, including transcription, translation, ciliogenesis, checkpoint
adaptation and recovery, apoptosis, chromosomes dynamics etc. Recent reviews have
tried to define the regulatory role of PLK-1 during mitosis progression and
tumorigenesis, but its' functional role beyond mitosis is still largely
unexplored. PLK-1 can regulate the activity of many proteins that work outside of
its conventional territory. The dysregulation of these proteins can cause
diseases such as Alzheimer's disease, tumorigenesis etc. and may also lead to
drug resistance. Thus, in this review, we discussed the versatile role of PLK-1
and tried to collect data to validate its' functional role in cell cycle
regulation apart from mitosis.
PMID- 28415811
TI - IL-33/ST2-mediated inflammation in macrophages is directly abrogated by IL-10
during rheumatoid arthritis.
AB - IL-10 is an immunosuppressive cytokine produced and sensed by many immune cells
and exerts a protective role in autoimmune diseases. However, the underlying
mechanism by which IL-10 contributes to prevent the arthritic inflammation in
macrophages is poorly understood. Herein we report on a novel anti-arthritic
property of IL-10 through the inhibition of IL-33 signaling by macrophages during
collagen-induced arthritis (CIA) development. We show that IL-33 expression
rather than its receptor (ST2) is positively correlated with IL-10 level in
active RA. IL-10 deficiency in mice leads to significant upregulation of IL-33
expression and aggravates the progression of CIA, while exogenous IL-10 treatment
effectively diminishes IL-33 production in IL-10 knockout (IL-10-/-) CIA mice. We
demonstrate further that the inhibitory effect of IL-10 in suppressing IL-33
production requires STAT3 activation in macrophages. Furthermore, IL-33
stimulated proinflammatory genes are notably increased in IL-10-/- CIA mice,
whereas macrophages treated with recombinant IL-10 exhibit decreased IL-33
amplified inflammation and inhibited IL-33 activated NF-kappaB signaling pathway.
Our findings indicate that IL-10 act as a negative regulator of IL-33/ST2
signaling pathways in vivo, suggesting a potential therapeutic role of IL-10 in
autoimmune diseases.
PMID- 28415814
TI - Concurrent chemo-radiotherapy with S-1 as an alternative therapy for elderly
Chinese patients with non-metastatic esophageal squamous cancer: evidence based
on a systematic review and meta-analysis.
AB - OBJECTIVE: This systematic review and meta-analysis aims to systematically assess
the effects of concurrent chemo-radiotherapy (CRT) compared with radiotherapy
(RT) alone for elderly Chinese patients with non-metastatic esophageal squamous
cancer. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of
Controlled Trials (CENTRAL), China Biomedical Literature Database (CBM), and
China National Knowledge Infrastructure (CNKI) databases. We retrieved randomized
controlled trials on concurrent CRT with Gimeraciland Oteracil Porassium (S-1)
compared with RT alone for aged Chinese patients with non-metastatic esophageal
squamous cancer performed until August 2016. RESULTS: Eight eligible studies
involving 536 patients were subjected to meta-analysis. As a response rate
measure, a relative risk (RR) of 1.37 [95% confidence intervals (CIs): 1.24,
1.53; P = 0.00], which reached statistical significance, was estimated when
concurrent CRT with S-1 was performed compared with RT alone. Sensitivity
analysis on response rate confirmed the robustness of the pooled result. The RR
values of 1.44 (95% CIs: 1.22, 1.70; P = 0.00) and 1.77 (95% CIs: 1.26, 2.48; P =
0.00) estimated for 1- and 2-year survival rate indices, respectively, were also
statistically significant. The incidence of adverse events was similar in both
groups. CONCLUSION: This review concluded that concurrent CRT with S-1 can
improve the efficacy and prolong the survival period of elderly Chinese patients
with non-metastatic esophageal squamous cancer and does not significantly
increase the acute adverse effects of RT alone.
PMID- 28415812
TI - Signal transduction growth factors: the effective governance of transcription and
cellular adhesion in cancer invasion.
AB - Giulio Bizzozero classified the tissues concerning their capacity to self-renew
during the adult life in labile, stable and permanent tissues. In 1940 Viktor
Hamburger and Rita Levi Montalcini exposed the possibility to induce the growth
of permanent cells thanks to a specific ligand Nerve Growth Factor (NGF). Stanley
Cohen purified a protein the Epidermal Growth Factor (EGF), able to induce
epidermis proliferation and to elicit precocious eye disclosure and teeth
eruption, establishing the "inverse" relationships between the proliferation and
differentiation. These two biological effects induced by EGF were according to
EGFR signaling is involved in a large array of cellular functions such as
proliferation, survival, adhesion, migration and differentiation. This review is
focused on the key role of growth factors signaling and their downstream
effectors in physiological and in pathological phenomena, the authors highlight
the governance of Growth factors during the EMT in cancer invasion.
PMID- 28415815
TI - BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast
cancer.
AB - PURPOSE: To determine whether the clinicopathological parameters and Breast
Imaging Reporting and Data System (BI-RADS) 3-5 microcalcifications differed
between lymph node positive (LN (+)) and lymph node negative (LN (-)) invasive
ductal carcinoma (IDC). RESULTS: For microcalcification-associated breast
cancers, seven selected features (age, tumor size, Ki-67 status, lymphovascular
invasion, calcification range, calcification diameter and calcification density)
were significantly associated with LN status (all P < 0.05). Multivariate
logistic regression analysis found that three risk factors (age: older vs.
younger OR: 0.973 P = 0.006, tumor size: larger vs. smaller OR: 1.671, P < 0.001
and calcification density: calcifications > 20/cm2 vs. calcifications <= 20/cm2
OR: 1.698, P < 0.001) were significant independent predictors. This model had an
area under the receiver operating characteristic curve (AUC) of 0.701. The nodal
staging (N0 and N1 chi2 = 5.701, P = 0.017; N0 and N2 chi2 = 6.614, P = 0.013)
was significantly positively associated with calcification density. The luminal B
subtype had the highest risk of LN metastasis. Multivariate analysis demonstrated
that calcification > 2 cm in range (OR: 2.209) and larger tumor size (OR: 1.882)
were independently predictive of LN metastasis in the luminal B subtype (AUC =
0.667). MATERIALS AND METHODS: Mammographic images of 419 female breast cancer
patients were included. Associations between the risk factors and LN status were
evaluated using a Chi-square test, ANOVA and binary logistic regression analysis.
CONCLUSIONS: This study found that age, tumor size and calcifications density can
be conveniently used to facilitate the preoperative prediction of LN metastasis.
The luminal B subtype has the highest risk of LN metastasis among the
microcalcification-associated breast cancers.
PMID- 28415816
TI - Targeting the PIM protein kinases for the treatment of a T-cell acute
lymphoblastic leukemia subset.
AB - New approaches are needed for the treatment of patients with T-cell acute
lymphoblastic leukemia (T-ALL) who fail to achieve remission with chemotherapy.
Analysis of the effects of pan-PIM protein kinase inhibitors on human T-ALL cell
lines demonstrated that the sensitive cell lines expressed higher PIM1 protein
kinase levels, whereas T-ALL cell lines with NOTCH mutations tended to have lower
levels of PIM1 kinase and were insensitive to these inhibitors. NOTCH-mutant
cells selected for resistance to gamma secretase inhibitors developed elevated
PIM1 kinase levels and increased sensitivity to PIM inhibitors. Gene profiling
using a publically available T-ALL dataset demonstrated overexpression of PIM1 in
the majority of early T-cell precursor (ETP)-ALLs and a small subset of non-ETP
ALL. While the PIM inhibitors blocked growth, they also stimulated ERK and STAT5
phosphorylation, demonstrating that activation of additional signaling pathways
occurs with PIM inhibitor treatment. To block these pathways, Ponatinib, a
broadly active tyrosine kinase inhibitor (TKI) used to treat chronic myelogenous
leukemia, was added to this PIM-inhibitor regimen. The combination of Ponatinib
with a PIM inhibitor resulted in synergistic T-ALL growth inhibition and marked
apoptotic cell death. Treatment of mice engrafted with human T-ALL with these two
agents significantly decreased the tumor burden and improved the survival of
treated mice. This dual therapy has the potential to be developed as a novel
approach to treat T-ALL with high PIM expression.
PMID- 28415817
TI - An updated meta-analysis of 23 case-control studies on the association between
miR-34b/c polymorphism and cancer risk.
AB - The association between in microRNA-34b/c gene rs4938723 polymorphisms and cancer
risk remains inconclusive. This meta-analysis was performed to analyze the
association between microRNA-34b/c rs4938723 polymorphism and risk for cancer
development. In total, 304 studies from PubMed, Embase, Web of Science, Wanfang,
and Chinese National Knowledge Infrastructure databases were examined, and 23
studies were included in this meta-analysis. The 23 selected studies involved
10,812 cancer cases and 11,719 controls. Odds ratios (ORs) and 95% confidence
intervals (CIs) were calculated to measure the strength of the association. Our
results indicate a significant association between the rs4938723 polymorphism and
cancer risk in the overdominant model (P heterogeneity = 0.018, OR = 1.093, and
95% CI = 1.015-1.177 for CT vs. CC/TT). Using a stratified subgroup analysis,
rs4938723 polymorphisms were associated with an increased risk for hepatocellular
carcinoma, but decreased risk for colorectal, gastric, and esophageal squamous
cell cancer. These findings indicate that the rs4938723 gene is a susceptible
locus for cancer.
PMID- 28415818
TI - Mechanistic characterization of a copper containing thiosemicarbazone with potent
antitumor activity.
AB - BACKGROUND: The thiosemicarbazone CD 02750 (VLX50) was recently reported as a hit
compound in a phenotype-based drug screen in primary cultures of patient tumor
cells. We synthesized a copper complex of VLX50, denoted VLX60, and characterized
its antitumor and mechanistic properties. MATERIALS AND METHODS: The cytotoxic
effects and mechanistic properties of VLX60 were investigated in monolayer
cultures of multiple human cell lines, in tumor cells from patients, in a 3-D
spheroid cell culture system and in vivo and were compared with those of VLX50.
RESULTS: VLX60 showed >= 3-fold higher cytotoxic activity than VLX50 in 2-D
cultures and, in contrast to VLX50, retained its activity in the presence of
additional iron. VLX60 was effective against non-proliferative spheroids and
against tumor xenografts in vivo in a murine model. In contrast to VLX50, gene
expression analysis demonstrated that genes associated with oxidative stress were
considerably enriched in cells exposed to VLX60 as was induction of reactive
oxygen. VLX60 compromised the ubiquitin-proteasome system and was more active in
BRAF mutated versus BRAF wild-type colon cancer cells. CONCLUSIONS: The cytotoxic
effects of the copper thiosemicarbazone VLX60 differ from those of VLX50 and
shows interesting features as a potential antitumor drug, notably against BRAF
mutated colorectal cancer.
PMID- 28415819
TI - Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen
resistance in estrogen receptor-positive breast cancer cells.
AB - Tamoxifen is still the most commonly used endocrine therapy drug for estrogen
receptor (ER)-positive breast cancer patients and has an excellent outcome, but
tamoxifen resistance remains a great impediment to successful treatment. Recent
studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that
aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF
7, especially when combined with tamoxifen, but also has a potential function to
overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can
down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen
alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line
but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the
expression of these proteins in the resistant cell line. When knocking down c-myc
in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as
well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to
overcome tamoxifen resistance. Our study discovered a novel role of aspirin based
on its anti-tumor effect, and put forward some kinds of possible mechanisms of
tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy
for the treatment of ER-positive breast carcinoma.
PMID- 28415820
TI - Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells.
AB - Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is
expressed on tumor cells that suppresses the T cell-mediated immune response.
Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown
promising results in some types of cancers. However, the functional and
therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study,
we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue
microarray of patient tumors. Tissue microarray immunohistochemistry analysis
showed that the overall and five-year survival rates of patients with high levels
of PD-L1 expression were significantly shorter than patients with low levels.
High levels of PD-L1 expression were also associated with metastasis in
osteosarcoma patients. Furthermore, we applied the Clustered Regularly
Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene
at the DNA level in osteosarcoma cell lines. We found that the expression of PD
L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown
increased drug sensitivities for doxorubicin and paclitaxel. These results
suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that
PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of
osteosarcoma.
PMID- 28415821
TI - Deep sequencing-based microRNA expression signatures in head and neck squamous
cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs.
AB - We adopted into RNA-sequencing technologies to construct the microRNA (miRNA)
expression signature of head and neck squamous cell carcinoma (HNSCC). Our
signature revealed that a total of 160 miRNAs (44 upregulated and 116
downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150
5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were
significantly silenced in cancer tissues, suggesting both miRNAs act as antitumor
miRNAs in HNSCC cells. Ectopic expression of mature miRNAs, miR-150-5p and miR
150-3p inhibited cancer cell aggressiveness. Low expression of miR-150-5p and miR
150-3p predicted significantly shorter overall survival in patients with HNSCC (P
= 0.0091 and P = 0.0386) by Kaplan-Meier survival curves analyses. We identified
that integrin alpha3 (ITGA3), integrin alpha6 (ITGA6), and tenascin C (TNC) were
coordinately regulated by these miRNAs in HNSCC cells. Knockdown assays using
siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC
cells. Moreover, ITGA3, ITGA6, and TNC alterations were associated with
significantly poorer overall survival (P = 0.0177, P = 0.0237, and P = 0.026,
respectively). Dual strands of pre-150 (miR-150-5p and miR-150-3p) functioned as
antitumor miRNAs based on the miRNA expression signature of HNSCC. Identification
of antitumor miR-150-mediated RNA networks may provide novel insights into
pathogenesis of HNSCC.
PMID- 28415822
TI - Interaction between granulin A and enolase 1 attenuates the migration and
invasion of human hepatoma cells.
AB - Granulin A (GRN A), a peptide with a molecular 6 kDa, is derived from proteolysis
of progranulin (PGRN). Previous study in our laboratory has shown that GRN A is
able to inhibit cancer cell growth significantly. In the present study, we
confirmed that GRN A can bind to alpha-enolase (ENO1) specifically as analyzed
using Pull-down/MS approaches. The interaction of GRN A with ENO1 was further
confirmed by Western blotting and Surface plasmon resonance (SPR) analysis.
Treatment of human HepG-2 cells with GRN A inhibited cancer cell growth as well
as migration and invasion of cancer cells as analyzed by the 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) and Scratch wound
healing assay as well as Transwell experiments. Additionally, GRN A treatment
results in augmentation of glucose uptake in cancer cells. Further study reveals
that higher expression of ENO1 reversed the inhibitory effects of GRN A on
migration and invasion of HepG-2 cells. The increase of glucose uptake, as well
as the expression of apoptosis-related genes, is also reversed in cells
overexpressing ENO1. The study provides solid evidence that there is the
interaction between GRN A and ENO1 and the interaction is responsible for the
effects of GRN A on glucose uptake as well as cancer cell migration and invasion.
PMID- 28415823
TI - Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells.
AB - Traditional gene fusions are involved in the development of various neoplasia.
DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-fusion in
prostate and gastric cancer, in addition to playing a tumorigenic role. Here, we
showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal
tissues. It is also present in non-cancer epithelial, as well as in fibroblast
cell lines. Quantitatively, the fusion transcript has a comparable expression in
non-cancerous, gastric and prostate cell lines and tissues as in the cancer cell
lines and tissues. The loss-of-function approach as previously reported is not
sufficient to prove the functionality of the fusion. On the other hand, the gain
of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell
growth and motility, even in non-cancer cells. Finally, we provide further
evidence that the fusion transcript is a product of cis-splicing between adjacent
genes. In summary, we believe that in contrast to traditional gene fusions, DUS4L
BCAP29 cannot be used as a cancer biomarker. Instead, it is a fusion transcript
that exists in normal physiology and that its pro-growth effect is not unique to
cancer cells.
PMID- 28415824
TI - Influence of marital status on the survival of adults with
extrahepatic/intrahepatic cholangiocarcinoma.
AB - Although the prognostic value of marital status has been implicated in many
cancers, its prognostic impact on cholangiocarcinoma has not yet been determined.
The aim of this study was to examine the association between marital status and
cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma
cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from
the Surveillance, Epidemiology, and End Results database. We found widowed
patients were more likely to be female, aged more than 70, and from low income
areas. Multivariate analysis indicated that marital status was an independent
prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis
suggested the widowed status independently predicted poor survival at regional
stage and in older patients with intrahepatic cholangiocarcinoma. To conclude,
marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed
patients are at greater risk of death than others.
PMID- 28415825
TI - Recombinant human erythropoietin stimulates melanoma tumor growth through
activation of initiation factor eIF4E.
AB - Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer
patients. Recent clinical trials suggest that EPO may accelerate tumor
progression and increase mortality. However, the evidence supporting a growth
promoting effect of EPO has remained controversial. Employing an in vivo model of
B16 murine melanoma, we observed that administration of EPO to tumor bearing
C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro
studies demonstrate that B16 murine melanoma cells express EPOR, both at the
protein and mRNA levels. Interestingly, expression of EPOR was retained in the
established tumors. EPO stimulation of B16 cells enhanced proliferation and
protein synthesis rates, and correlated with activation of the receptor
associated Janus kinase 2 (Jak2) as well as phosphorylation of extracellular
signal-regulated kinase (Erk) 1/2 and Akt kinases. Treatment with EPO and Jak-2
antagonists significantly inhibited EPO-mediated B16 cell proliferation.
Moreover, EPO dose-dependently induced the phosphorylation and activation of the
translation initiation factor eIF4E as well as the phosphorylation of its
repressor, the eIF4E binding protein 4E-BP1. Finally, using eIF4E small
interfering RNA (siRNA), we observed that EPO-mediated stimulation of B16 cell
proliferation is eIF4E-dependent. Our results indicate that EPO exerts a powerful
stimulatory effect on cell proliferation and de novo protein synthesis in
melanoma cells through activation of the initiation factor eIF4E.
PMID- 28415826
TI - Azithromycin augments rhinovirus-induced IFNbeta via cytosolic MDA5 in
experimental models of asthma exacerbation.
AB - Deficient production of anti-viral interferons (IFNs) may be involved in causing
viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production
would be warranted. Azithromycin may reduce asthma exacerbations but its modus
operandi is unknown. Here, we investigated if azithromycin induces IFNbeta
expression in vitro in rhinovirus-infected bronchial epithelial cells from
asthmatic donors and in vivo in our allergic inflammation-based mouse model of
viral stimulus-induced asthma exacerbations. Azithromycin dose-dependently
augmented viral-induced IFNbeta expression in asthmatic, but not in healthy
bronchial epithelial cells. The effect negatively correlated with viral load.
Knockdown of MDA5 and RIG-I by siRNA showed involvement of MDA5 but not RIG-I in
azithromycin's IFN-inducing effects in vitro. In vivo azithromycin induced
IFNbeta protein, restoring a reduced lung IFN response exclusively in allergic
exacerbating mice. This was associated with induction of interferon-stimulated
genes and MDA5, but not RIG-I. We suggest that clinically relevant concentrations
of azithromycin produce MDA5-dependent, anti-viral, IFN-inducing effects in
bronchial epithelium distinctly from asthmatic donors. Similarly, azithromycin
induced MDA5-associated IFN in virally stimulated lungs in vivo exclusively in
allergic mice. Effects of azithromycin and MDA5-active drugs on viral-induced
exacerbations deserve further research.
PMID- 28415827
TI - Camptothecin resistance is determined by the regulation of topoisomerase I
degradation mediated by ubiquitin proteasome pathway.
AB - Proteasomal degradation of topoisomerase I (topoI) is one of the most remarkable
cellular phenomena observed in response to camptothecin (CPT). Importantly, the
rate of topoI degradation is linked to CPT resistance. Formation of the topoI-DNA
CPT cleavable complex inhibits DNA re-ligation resulting in DNA-double strand
break (DSB). The degradation of topoI marks the first step in the ubiquitin
proteasome pathway (UPP) dependent DNA damage response (DDR). Here, we show that
the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein
kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is
subsequently ubiquitinated by BRCA1. A higher basal level of topoI-pS10 ensures
rapid topoI degradation leading to CPT resistance. Importantly, PTEN regulates
DNA-PKcs kinase activity in this pathway and PTEN deletion ensures DNA-PKcs
dependent higher topoI-pS10, rapid topoI degradation and CPT resistance.
PMID- 28415830
TI - Triptolide mitigates radiation-induced pneumonitis via inhibition of alveolar
macrophages and related inflammatory molecules.
AB - Ionizing radiation-induced pulmonary injury is a major limitation of radiotherapy
for thoracic tumors. We have demonstrated that triptolide (TPL) could alleviate
IR-induced pneumonia and pulmonary fibrosis. In this study, we explored the
underlying mechanism by which TPL mitigates the effects of radiotoxicity. The
results showed that:(1) Alveolar macrophages (AMs) were the primary inflammatory
cells infiltrating irradiated lung tissues and were maintained at a high level
for at least 17 days, which TPL could reduce by inhibiting of the production of
macrophage inflammatory protein-2 (MIP-2) and its receptor CXCR2.(2) Stimulated
by the co-cultured irradiated lung epithelium, AMs produced a panel of
inflammative molecules (IMs), such as cytokines (TNF-alpha, IL-6, IL-1alpha, IL
1beta) and chemokines (MIP-2, MCP-1, LIX). TPL-treated AMs could reduce the
production of these IMs. Meanwhile, AMs isolated from irradiated lung tissue
secreted significantly high levels of IMs, which could be dramatically reduced by
TPL.(3) TPL suppressed the phagocytosis of AMs as well as ROS production.Our
results indicate that TPL mitigates radiation-induced pulmonary inflammation
through the inhibition of the infiltration, IM secretion, and phagocytosis of
AMs.
PMID- 28415833
TI - Molecular Characterization and Biodiversity of a Putative Chlorotoxin from the
Iranian Yellow Scorpion Odontobuthus doriae
AB - BAckground: Chloride channels have already been over-expressed in the different
types of cancer. Chlorotoxins, as the blocking agent of these channels, have been
indicated to be an effective drug against tumors. In this study, we characterized
a putative chlorotoxin from a cDNA library of the venom glands obtained from the
Iranian scorpion Odontobuthus doriae. Methods: A cDNA library was constructed
from venom gland transcriptome of six scorpions. The cDNA encoding Odontobuthus
doriae chlorotoxin was isolated from the library, and its putative peptide was
characterized by some bioinformatics software such as protein blast, SignalP4.0,
DISULFIND and Clustal Omega. Results: The mature Odontobuthus doriae chlorotoxin
peptide has a 35-amino-acid residue and four disulfide bounds. This putative
chlorotoxin is a small, compact, and stable molecule. Moreover, based on the open
reading frame sequence similarity, this peptide is similar to Buthus martensii
Karsch chlorotoxin like toxin and Bm12-b neurotoxins from the Chinese scorpion
Mesobuthus martensii. Conclusion: The small size of this putative chlorotoxin and
its stability make it as a suitable candidate for medical and pharmacological
research, especially in the cancer research.
PMID- 28415831
TI - Definitive radiochemotherapy versus surgery within multimodality treatment in
stage III non-small cell lung cancer (NSCLC) - a cumulative meta-analysis of the
randomized evidence.
AB - Randomized trials were analyzed comparing surgery with definitive radiotherapy as
local curative treatment options within the framework of different multimodality
treatments for patients with locally advanced non-small cell lung cancer (NSCLC).
Endpoints for comparison of treatment results were overall survival, progression
free survival, and toxicity.Hazard ratios (HR) were taken to measure treatment
effects and pooled using a random effects model.Overall survival was not
significantly different between surgical and definitive radiotherapy arms
(HR=0.92 [95%CI 0.82-1.04], p=0.19, chi2-test). There was heterogeneity with
respect to survival at 2 years (p<0.0001, Cochran Mantel Haenszel (CMH)-test).
Latter trials using concurrent radiochemotherapy (ccRT/CT) showed better survival
at 2 years (risk ratio of death=0.80 [95%CI 0.73-0.88], p<0.0001, CMH-test). In
the ccRT/CT trials, survival in the surgical arms tended to have an excess early
mortality before 6 months of follow-up and a lesser hazard rate in comparison to
definitive ccRT/CT thereafter (HR=0.78 [95%CI 0.63-0.98]). Over all trials,
treatment associated mortality was higher in the surgical arms (risk ratio=3.56
[95% CI: 1.65-7.72], p=0.0005, CMH test). With respect to progression-free
survival, no significant differences were found (HR=0.91 [95%CI: 0.73 - 1.13]),
although the largest conducted trial found an advantage for the surgical arm
(HR=0.77 [95%CI: 0.62-0.96]).Induction therapy followed by resection or
definitive radiochemotherapy represent valuable curative treatment options for
patients with stage III NSCLC, the individual treatment choice deserves careful
interdisciplinary evaluation and counseling. Based on the broad heterogeneity of
patient groups in these stages further research on predictive factors supporting
individual therapy selection is necessary.
PMID- 28415828
TI - Melatonin for the prevention and treatment of cancer.
AB - The epidemiological studies have indicated a possible oncostatic property of
melatonin on different types of tumors. Besides, experimental studies have
documented that melatonin could exert growth inhibition on some human tumor cells
in vitro and in animal models. The underlying mechanisms include antioxidant
activity, modulation of melatonin receptors MT1 and MT2, stimulation of
apoptosis, regulation of pro-survival signaling and tumor metabolism, inhibition
on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin
could also be utilized as adjuvant of cancer therapies, through reinforcing the
therapeutic effects and reducing the side effects of chemotherapies or radiation.
Melatonin could be an excellent candidate for the prevention and treatment of
several cancers, such as breast cancer, prostate cancer, gastric cancer and
colorectal cancer. This review summarized the anticancer efficacy of melatonin,
based on the results of epidemiological,experimental and clinical studies, and
special attention was paid to the mechanisms of action.
PMID- 28415834
TI - The surgical treatment of gastric cancer in the era of minimally invasive
surgery.
AB - Minimally invasive surgery is regarded as an alternative to conventional open
surgery in gastric cancer. More and more surgeons devote their efforts to reduce
surgical incision and acquire better recovery. Nowadays, laparoscopic distal
gastrectomy has been the standard method for early stage cancer with remarkable
advantage in short-term outcomes and is widely accepted by patients. The
indication of laparoscopic gastrectomy has been extended to local advanced
gastric cancer. However, the oncological safety has long been debated. Therefore,
large scale randomized controlled clinical trials are ongoing to confirm the
feasibility and safety in more advanced gastric cancer. With the accumulation of
surgical experience and development of instrument, several advanced techniques,
such as function preserving surgery, total laparoscopic anastomosis, sentinel
node navigation surgery, robotic assisted surgery and reduced port laparoscopic
gastrectomy have also been explored and applied to gastric cancer patient. All
these techniques could modify the extent of surgery, reduce the risk of
perioperative complications and generate potential better results in quality of
life. Although recent studies have confirmed the feasibility and safety of each
procedure, more evidence is required for further popularization of the newly
technique. Herein we describe the current status and evidence for surgical
treatment of gastric cancer in the era of minimally invasive surgery.
PMID- 28415835
TI - The role of chemotherapy in unresectable or metastatic adenocarcinoma of the
stomach and gastroesophageal junction.
AB - Gastric cancer including gastroesophageal junction adenocarcinomas are most
challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has
a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly
diagnosed patients will have disseminated disease and in need of systemic
therapy. Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with
differences in geographical distribution, histopathology, and molecular subtypes.
Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin,
oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory
irinotecan are active drugs against AGC. The combination of fluoropyrimidines
with a platinum compound is the optimal first-line treatment. Trastuzumab (given
in combination with chemotherapy for HER2 positive tumors) and ramucirumab are
the only targeted agents approved by the food and drug administration for the
treatment in AGC for first and second line respectively. Efforts are being
directed to harness the immune system with checkpoint inhibitors and to combining
these drugs with chemotherapy in clinical trials. Genomic technology advancements
might provide us with the tools to create personalized treatment for AGC in the
near future with the goal to improve outcomes. In this article we aimed to review
current therapeutic regimens for AGC with an update of ongoing clinical trials.
PMID- 28415837
TI - Effects of a Spacer on the Phase Behavior of Gemini Surfactants in
Ethanolammonium Nitrate.
AB - The aggregation behavior of quaternary ammonium gemini surfactants (12-s-12) in a
protic ionic liquid, ethanolammonium nitrate (EOAN), was investigated by small
angle X-ray scattering, freeze-fracture transmission electron microscopy,
polarized optical microscopy, and rheological measurements. The rarely reported
nonaqueous two phases in the ionic liquid were observed at lower 12-s-12
concentrations. The upper phase was composed of micelles, whereas only the
surfactant unimers or multimers were detected in the low phase. At higher 12-s-12
concentrations, different aggregates were formed. The lamellar phase was observed
in the 12-2-12/EOAN system, whereas the normal hexagonal phases in 12-s-12/EOAN
(s = 3, 4, 5, 6, 8) systems and the micellar phase in the 12-10-12/EOAN system
were observed. Such a dramatic phase transition induced by the spacer chain
length was due to the unique solvent characteristics of EOAN compared to those of
water and its counterpart ethylammonium nitrate.
PMID- 28415838
TI - A Fluorescent Probe for Hydrogen Peroxide in Vivo Based on the Modulation of
Intramolecular Charge Transfer.
AB - Endogenous hydrogen peroxide in vivo is related to many diseases, including
cancer, diabetes, cardiovascular disease, and neurodegenerative disorders.
Although many probes for detection of H2O2 have been explored, rapid response
probes are still expected for in vivo application. Here, a new probe (PAM-BN-PB)
was designed based on an intramolecular charge transfer (ICT) process with three
parts: phenanthroimidazole, benzonitrile, and phenyl boronate. By modulation ICT
process of PAM-BN-PB, H2O2 in solution systems can be detected with good
selectivity. The exogenous and endogenous H2O2 in normal living cells, ischemia
reperfusion injury cells, and animals all can be imaged by PAM-BN-PB.
PMID- 28415836
TI - Diabetic cardiomyopathy: where we are and where we are going.
AB - The global burden of diabetes mellitus and its related complications are
currently increasing. Diabetes mellitus affects the heart through various
mechanisms including microvascular impairment, metabolic disturbance, subcellular
component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune
response. Eventually, diabetes mellitus can cause functional and structural
changes in the myocardium without coronary artery disease, a disorder known as
diabetic cardiomyopathy (DCM). There are many diagnostic tools and management
options for DCM, although it is difficult to detect its development and
effectively prevent its progression. In this review, we summarize the current
research regarding the pathophysiology and pathogenesis of DCM. Moreover, we
discuss emerging diagnostic evaluation methods and treatment strategies for DCM,
which may help our understanding of its underlying mechanisms and facilitate the
identification of possible new therapeutic targets.
PMID- 28415839
TI - Enantioselective Synthesis of anti-syn-Trihalides and anti-syn-anti-Tetrahalides
via Asymmetric beta-Elimination.
AB - Structural motifs containing contiguous halide-bearing stereocenters are common
in natural products as well as bioactive molecules. A few successful examples
have been reported in the area of asymmetric vicinal dihalogenation of alkenes
for accessing dihalogenated products; in this report, an alternative generation
method of contiguous halide-bearing stereocenters alpha,beta,gamma,delta relative
to carbonyl group in excellent enantioselectivity is proposed by utilizing a
Song's oligoEG catalyst-catalyzed asymmetric beta-elimination. According to this
methodology, a wide range of anti-syn-trihalides and anti-syn-anti-tetrahalides
with high levels of enantioselectivity were synthesized. The synthetic utility of
the contiguous halide-bearing stereocenters was demonstrated by several
transformations. The results of high-resolution mass spectrometry indicated that
the favorable interaction between catalyst and one of the enantiomers of racemic
contiguously multihalogenated ketone contributed to the original
enantioselectivity of dehydrohalogenation. A deuterium kinetic isotope effect
experiment revealed that this beta-elimination reaction proceeds by the E2
mechanism. This strategy opens a new pathway for the asymmetric synthesis of
contiguous halide-bearing stereocenters of great complexity.
PMID- 28415840
TI - Coexistence of Topological Edge State and Superconductivity in Bismuth Ultrathin
Film.
AB - Ultrathin freestanding bismuth film is theoretically predicted to be one kind of
two-dimensional topological insulators. Experimentally, the topological nature of
bismuth strongly depends on the situations of the Bi films. Film thickness and
interaction with the substrate often change the topological properties of Bi
films. Using angle-resolved photoemission spectroscopy, scanning tunneling
microscopy or spectroscopy and first-principle calculation, the properties of
Bi(111) ultrathin film grown on the NbSe2 superconducting substrate have been
studied. We find the band structures of the ultrathin film is quasi-freestanding,
and one-dimensional edge state exists on Bi(111) film as thin as three bilayers.
Superconductivity is also detected on different layers of the film and the
pairing potential exhibits an exponential decay with the layer thicknesses. Thus,
the topological edge state can coexist with superconductivity, which makes the
system a promising platform for exploring Majorana Fermions.
PMID- 28415841
TI - Unique Pattern of Protein-Bound Maillard Reaction Products in Manuka
(Leptospermum scoparium) Honey.
AB - As a unique feature, honey from the New Zealand manuka tree (Leptospermum
scoparium) contains substantial amounts of dihydroxyacetone (DHA) and
methylglyoxal (MGO). Although MGO is a reactive intermediate in the Maillard
reaction, very little is known about reactions of MGO with honey proteins. We
hypothesized that the abundance of MGO should result in a particular pattern of
protein-bound Maillard reaction products (MRPs) in manuka honey. A protein-rich
high-molecular-weight fraction was isolated from 12 manuka and 8 non-manuka
honeys and hydrolyzed enzymatically. By HPLC-MS/MS, 8 MRPs, namely, N-epsilon
fructosyllysine, N-epsilon-maltulosyllysine, carboxymethyllysine,
carboxyethyllysine (CEL), pyrraline, formyline, maltosine, and methylglyoxal
derived hydroimidazolone 1 (MG-H1), were quantitated. Compared to non-manuka
honeys, the manuka honeys were characterized by high concentrations of CEL and MG
H1, whereas the formation of N-epsilon-fructosyllysine was suppressed, indicating
concurrence reactions of glucose and MGO at the epsilon-amino group of protein
bound lysine. Up to 31% of the lysine and 8% of the arginine residues,
respectively, in the manuka honey protein can be modified to CEL and MG-H1,
respectively. CEL and MG-H1 concentrations correlated strongly with the MGO
concentration of the honeys. Manuka honey possesses a special pattern of protein
bound MRPs, which might be used to prove the reliability of labeled MGO levels in
honeys and possibly enable the detection of fraudulent MGO or DHA addition to
honey.
PMID- 28415842
TI - Spectrophotometric Quantification of Peroxidase with p-Phenylene-diamine for
Analyzing Peroxidase-Encapsulating Lipid Vesicles.
AB - A spectrophotometric assay for the determination of horseradish peroxidase (HRP)
in aqueous solution with p-phenylenediamine (PPD, benzene-1,4-diamine) as
electron donor substrate and hydrogen peroxide (H2O2) as oxidant was developed.
The oxidation of PPD by HRP/H2O2 leads to the formation of Bandrowski's base
((3E,6E)-3,6-bis[(4-aminophenyl)imino]cyclohexa-1,4-diene-1,4-diamine), which can
be quantified by following the increase in absorbance at 500 nm. The assay was
applied for monitoring the activity of HRP inside ~180 nm-sized lipid vesicles
(liposomes), prepared from POPC (1-palmitoyl-2-oleoyl-sn-glycero-3
phosphocholine) and purified by size exclusion chromatography. Because of the
high POPC bilayer permeability of PPD and H2O2, the HRP-catalyzed oxidation of
PPD occurs inside the vesicles once PPD and H2O2 are added to the vesicle
suspension. In contrast, if instead of PPD the bilayer-impermeable substrate
ABTS2- (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)) is used, the
oxidation of ABTS2- inside the vesicles does not occur. Therefore, using PPD and
ABTS2- in separate assays allows distinguishing between vesicle-trapped HRP and
HRP in the external bulk solution. In this way, the storage stability of HRP
containing POPC vesicles was investigated in terms of HRP leakage and activity of
entrapped HRP. It was found that pH 7.0 suspensions of POPC vesicles (2.2 mM
POPC) containing on average about 12 HRP molecules per vesicle are stable for at
least 1 month without any significant HRP leakage, if stored at 4 degrees C.
Such high stability is beneficial not only for bioanalytical applications but
also for exploring the kinetic properties of vesicle-entrapped HRP through simple
spectrophotometric absorption measurements with PPD as a sensitive and cheap
substrate.
PMID- 28415843
TI - Structure, Stability, and Electronic and Magnetic Properties of VGen (n = 1-19)
Clusters.
AB - We systematically study the equilibrium geometries and electronic and magnetic
properties of Gen+1 and VGen (n = 1-19) clusters using the density functional
theory approach within the generalized gradient approximation. Endohedral
structures in which the vanadium atom is encapsulated inside a Gen cage are
predicted to be favored for n >= 10. The dopant V atom in the Gen clusters has
not an immediate effect on the stability of small germanium clusters (n < 6), but
it largely contributes to strengthen the stability for n >= 7. Our study enhances
the large stability of the VGe14 cluster, which presents an Oh symmetry cagelike
geometry and a peculiar electronic structure in which the valence electrons of V
and Ge atoms are delocalized and exhibit a shell structure associated with the
quasi-spherical geometry. Consequently, this cluster is proposed to be a good
candidate to be used as the building blocks for developing new materials. The
cluster size dependence of the stability, the vertical ionization potentials, and
electron affinities of Gen+1 and VGen are presented. Magnetic properties and the
partial density of states of the most stable VGen clusters are also discussed.
PMID- 28415844
TI - Stimuli-Controlled Hydrogels and Their Applications.
PMID- 28415845
TI - What does 'rural return' mean? Rural-origin medical graduates do not 'go home'.
PMID- 28415847
TI - Synthesis and antitumour activity of arctigenin amino acid ester derivatives
against H22 hepatocellular carcinoma.
AB - Arctigenin (ARG) is famous in its abundant pharmacological activity. However,
many researches in it entered the bottleneck period because of its poor water
solubility. The derivatives of ARG have been synthesised with five amino acids
which have t-Butyloxy carbonyl (BOC) as a protective group. We examined the
effects of removing BOC. The results showed that the amino acid derivatives
without protective group have better water solubility and nitrite-clearing
ability than ARG. Based on these results, ARG6' and ARG9' were selected at a
dosage of 40 mg/kg to evaluate their antitumour activity. The percentage
inhibition rate of ARG6' and ARG9' were 55.87 and 51.40, respectively, which was
twice as much as ARG. Furthermore, they could increase liver and kidney indexes
and produce less damage in these organs. In brief, this study provides a basis
for new drug development.
PMID- 28415848
TI - Increased Carotid Intima-Media Thickness in Obstructive Sleep Apnea: An
Additional Issue to Consider.
PMID- 28415846
TI - Is urban-rural location associated with weight status in school children? An
examination of 42 small and rural Californian counties.
AB - INTRODUCTON: Studies have identified geographic variation in overweight and
obesity rates among children, with higher rates of overweight and obesity often
found among children living in rural compared to urban areas. A small number of
studies have explored differences in overweight and obesity based on more nuanced
gradations along the urban-rural continuum. The purpose of the present study was
to identify differences in overweight and obesity based on gradations along the
urban-rural continuum among children in 42 Californian counties with populations
less than 500 000. METHODS: An observational study was conducted using
FITNESSGRAM data collected from 5th, 7th and 9th grade students in public schools
in California during 2010-2011. The FITNESSGRAM dataset was merged with the 2011
Public Elementary/Secondary School Universe Survey Data from the National Center
for Educational Statistics Common Core of Data, which includes an 'urban-centric
locale' code for each school, consisting of four broad classifications - city,
suburb, town, and rural - each of which is further broken down into three
subcategories. Multivariate analyses using a general linear model were conducted
to compare differences in body mass index (BMI) between geographic regions of
schools (city, suburb, town and rural) as well as 11 urban-centric locale code
subcategories; none of the schools were located in large cities. The percentage
of students who were overweight and/or obese was compared by grade level, gender,
and race/ethnicity across geographic regions using multivariate logistic
regression models. Analyses were adjusted for student age, grade, gender,
race/ethnicity (African-American, Asian, Hispanic, Indian/Alaskan, White, two or
more races or unknown), eligibility for free or reduced price meals, and
clustering of students by school. When a stratified analysis was done, the
variable of stratification (ie grade, gender, race/ethnicity) was not included
among the covariates. When significant differences in BMI or prevalence of
overweight or obesity were found between geographic regions, Tukey's method was
applied to adjust for multiple comparisons at a 5% procedure-wise error rate. A
p-value at or less than 0.05 was used to indicate statistical
significance. RESULTS: Students in suburban schools had significantly lower mean
BMI and lower prevalence of overweight than students in other geographic areas
(p<0.0001). Among 5th and 7th grade students, prevalence of obesity (but
not overweight) varied by urban-rural status (p<0.0001, p=0.01,
respectively), with 7th grade students in suburbs having lower rates of obesity
than those in towns. Among 9th grade students, prevalence of overweight (but not
obesity) varied by urban-rural status (p=0.02). Among females, prevalence
of overweight and obesity varied (p=0.006, p<0.0001, respectively),
with suburbs having lower rates than cities and towns. Among males, prevalence of
obesity varied (p<0.0001), with suburbs having lower rates. Among whites,
there were differences in prevalence of overweight and obesity by urban-rural
status (p=0.01, p <0.0001, respectively). Among Hispanics, the
prevalence of obesity varied by urban-rural status (p=0.001). Large
suburban areas had the lowest rates of obesity compared to all other
subcategories. CONCLUSIONS: Students attending schools in suburban, especially
larger suburban, areas appear to have lower prevalence of obesity than their
peers at schools in other geographic areas. Further research is needed to
understand the factors associated with differences in weight status between
urban, suburban, town and rural areas.
PMID- 28415849
TI - Final Say on Research Into Population Screening for Abdominal Aortic Aneurysm.
PMID- 28415850
TI - A new iridoid glycoside from the fruits of Vitex rotundifolia.
AB - One new iridoid glycoside, 6',10-di-O-(4-hydroxybenzoyl) aucubin (1), together
with ten known compounds, including five diterpenoids (2-6), two triterpene
glucosides (7-8) and three methoxylated flavonoids (9-11) were isolated from the
fruits of Vitex rotundifolia. Compounds (3, 4, 7, and 8) were reported for the
first time from this plant. Their structures were elucidated by spectral analysis
and by comparison with literature data. Furthermore, some of the isolated
compounds were evaluated for their cytotoxicities against A549 and HepG-2 cell
lines using MTT assay, and only compounds 9 and 10 exhibited potent cytotoxic
activity with IC50 values of 13 +/- 4 and 35 +/- 10 MUM against HepG-2 cell
lines.
PMID- 28415851
TI - Over-education and well-being: how does education-occupation mismatch affect the
life satisfaction of university-educated immigrant and non-immigrant workers?
AB - OBJECTIVE: The increased migration of skilled workers has resulted in a focus on
the economic costs of their unsuccessful labor market integration. Few studies
investigate the consequences of employment difficulties on immigrants' well
being. Researchers studying over-education and life satisfaction tend to only
examine the general population despite high levels of over-education among
skilled immigrants. This study examines the relationship between over-education
and life satisfaction among both immigrant and native-born workers in Canada.
Factors associated with immigrants specifically (e.g. years since migration) are
also considered. DESIGN: Descriptive and multivariate analyses are conducted
using pooled data from the 2009 to 2014 Canadian Community Health Survey (CCHS).
Ordinary-least-squares (OLS) regression models are estimated with life
satisfaction as the outcome. The models are run separately for immigrant and
Canadian-born workers, accounting for differences in the degree to which
individuals are over-educated. There are 5826 immigrant respondents and 24,985
non-immigrant respondents. RESULTS: Over-education was negatively associated with
the life satisfaction of both immigrants and non-immigrants, although the effect
was weaker among the immigrant population. Income was the main factor mediating
the negative relationship between over-education and life satisfaction among
immigrants. Moreover, the negative influence of over-education on life
satisfaction weakened with immigrants' increased residence in Canada. CONCLUSION:
Although over-education was negatively associated with immigrants' life
satisfaction, it had a stronger influence on the non-immigrant population. This
may be due to differences in the reference groups to which immigrants and non
immigrants compare themselves when assessing their life satisfaction; over
education may be less influential to immigrants' life satisfaction because it is
a common experience among immigrants. Additionally, over-education is less
detrimental to immigrants' life satisfaction with increased time in the host
country. This may be attributable to a shift in the importance immigrants assign
to the employment domain of their life over time.
PMID- 28415852
TI - Internal health locus of control predicts willingness to track health behaviors
online and with smartphone applications.
AB - Given rising technology use across all demographic groups, digital interventions
offer a potential strategy for increasing access to health information and care.
Research is lacking on identifying individual differences that impact willingness
to use digital interventions, which may affect patient engagement. Health locus
of control, the amount of control an individual believes they have over their own
health, may predict willingness to use mobile health (mHealth) applications
('apps') and online trackers. A cross-sectional study (n = 276) was conducted to
assess college students' health locus of control beliefs and willingness to use
health apps and online trackers. Internal and powerful other health locus of
control beliefs predicted willingness to use health apps and online trackers
while chance health locus of control beliefs did not. Individuals with internal
and powerful other health locus of control beliefs are more willing than those
with chance health locus of control beliefs to utilize a form of technology to
monitor or change health behaviors. Health locus of control is an easy-to-assess
patient characteristic providers can measure to identify which patients are more
likely to utilize mHealth apps and online trackers.
PMID- 28415853
TI - Promoting Parent and Child Physical Activity Together: Elicitation of Potential
Intervention Targets and Preferences.
AB - Promoting physical activities that involve both parents and their children would
be very useful to the improved health and well-being of families, yet coactivity
interventions have been particularly unsuccessful in past research. The purpose
of this study was to elicit the salient parental beliefs about coactivity framed
through theory of planned behavior in order to inform future intervention
content. A representative sample of Canadian parents ( N = 483) with children
aged 6 to 14 years completed belief elicitation measures of theory of planned
behavior, as well as coactivity and program preferences. Analyses included
content theming by physical activity belief and preference through tallies of the
percentages of parents endorsing each belief. Exploratory analyses of differences
in endorsed themes were conducted by parent (mother, father), age of child (6-10
years, 11-14 years), and sex of the child. The results showed that behavioral
beliefs about health, interpersonal and educational/learning opportunities and
control beliefs about lack of time, various incompatible parent/child factors,
parental health, and bad weather were dominant themes. Most of these themes did
not vary in endorsement by parent and child characteristics. By contrast,
preferences for various activities varied by parent and child characteristics,
yet parents overwhelmingly desired the activities to be outdoors, close to home,
after work, and originally delivered from community health professionals via
Internet or face-to face means. Overall, the findings provide several
considerations for specific targets to improve future physical activity
intervention approaches among parents and their children.
PMID- 28415854
TI - New phenolic acids from Salvia yunnanensis C.H.Wright.
AB - Two new phenolic acids, ethyl pro-lithospermate (1), n-butyl pro-lithospermate
(2) were isolated from Salvia yunnanensis C.H.Wright, along with nineteen known
compounds (3-21). The structures of the isolated compounds were elucidated on the
basis of extensive spectrometry and by comparing their physical and spectroscopic
data to the literature. Among them, compounds 11, 12 and 14-16 were firstly
isolated from S. yunnanensis C.H.Wright. Some of the isolated compounds were
evaluated for their neuroprotection. Compounds 10-12 showed significant
neuroprotective effects in PC12 cells and compounds 1, 4-7 displayed moderate
neuroprotective effects.
PMID- 28415855
TI - Predicting jet lag in long-haul cabin crew: The role of illness cognitions and
behaviour.
AB - OBJECTIVE: Established risk factors for jet lag are mostly physiological
including circadian preference, age, gender, the number of flight zones crossed
and to some extent direction of travel. Some research has also highlighted a role
for psychosocial factors including sleep, diet and 'circadian' health behaviours
and illness cognitions although this remains relatively untested. The aim of this
study was to evaluate the role of sleep, diet and illness cognitions in
predicting perceived jet lag amongst long-haul crew. DESIGN: Sixty long-haul crew
took part in a longitudinal study. Profile characteristics (including
chronotype), preparation strategies (sleep, eating and 'circadian' behaviours)
and illness cognitions were measured at baseline (before a trip). MAIN OUTCOME
MEASURES: Subjective jet lag (unidimensional and multidimensional) was measured
on the crews' second day off (post-trip). RESULTS: Hierarchical regression
analyses showed that unidimensional jet lag was predicted by the belief in a
cyclical timeline, whereas multidimensional jet lag was predicted by
multidimensional jet lag at baseline and to a lesser extent by identity. No role
was found for profile characteristics and preparation strategies. CONCLUSION:
Illness cognitions partly explain the experience of perceived jet lag in long
haul cabin crew indicating that jet lag is in part a psycho-social construct, not
just a biological one.
PMID- 28415856
TI - Gene and Variant Annotation for Mendelian Disorders in the Era of Advanced
Sequencing Technologies.
AB - Comprehensive annotations of genetic and noncoding regions and corresponding
accurate variant classification for Mendelian diseases are the next big challenge
in the new genomic era of personalized medicine. Progress in the development of
faster and more accurate pipelines for genome annotation and variant
classification will lead to the discovery of more novel disease associations and
candidate therapeutic targets. This ultimately will facilitate better patient
recruitment in clinical trials. In this review, we describe the trends in
research at the intersection of basic and clinical genomics that aims to increase
understanding of overall genomic complexity, complex inheritance patterns of
disease, and patient-phenotype-specific genomic associations. We describe the
emerging field of translational functional genomics, which integrates other
functional "-omics" approaches that support next-generation sequencing genomic
data in order to facilitate personalized diagnostics, disease management,
biomarker discovery, and medicine. We also discuss the utility of this integrated
approach for diagnostic clinics and medical databases and its role in the future
of personalized medicine.
PMID- 28415858
TI - Recent Advances in Mitochondrial Disease.
AB - Mitochondrial disease is a challenging area of genetics because two distinct
genomes can contribute to disease pathogenesis. It is also challenging clinically
because of the myriad of different symptoms and, until recently, a lack of a
genetic diagnosis in many patients. The last five years has brought remarkable
progress in this area. We provide a brief overview of mitochondrial origin,
function, and biology, which are key to understanding the genetic basis of
mitochondrial disease. However, the primary purpose of this review is to describe
the recent advances related to the diagnosis, genetic basis, and prevention of
mitochondrial disease, highlighting the newly described disease genes and the
evolving methodologies aimed at preventing mitochondrial DNA disease
transmission.
PMID- 28415859
TI - The missing link? The potential role of selenium in the development of liver
cancer and significance for the general population.
PMID- 28415860
TI - Computer-Mediated Social Support for Physical Activity: A Content Analysis.
AB - PURPOSE: Online fitness communities are a recent phenomenon experiencing growing
user bases. They can be considered as online social networks in which recording,
monitoring, and sharing of physical activity (PA) are the most prevalent
practices. They have added a new dimension to the social experience of PA in
which online peers function as virtual PA partners or supporters. However,
research into seeking and receiving computer-mediated social support for PA is
scarce. Our aim was to study to what extent using online fitness communities and
sharing physical activities with online social networks results in receiving
various types of online social support. METHOD: Two databases, one containing
physical activities logged with Strava and one containing physical activities
logged with RunKeeper and shared on Twitter, were investigated for occurrence and
type of social support, by means of a deductive content analysis. RESULTS:
Results indicate that social support delivered through Twitter is not
particularly extensive. On Strava, social support is significantly more
prevalent. Especially esteem support, expressed as compliments for the
accomplishment of an activity, is provided on both Strava and Twitter.
CONCLUSION: The results demonstrate that social media have potential as a
platform used for providing social support for PA, but differences among various
social network sites can be substantial. Especially esteem support can be
expected, in contrast to online health communities, where information support is
more common.
PMID- 28415861
TI - Atmospheric Aerosols: Clouds, Chemistry, and Climate.
AB - Although too small to be seen with the human eye, atmospheric particulate matter
has major impacts on the world around us, from our health to global climate.
Understanding the sources, properties, and transformations of these particles in
the atmosphere is among the major challenges in air quality and climate research
today. Significant progress has been made over the past two decades in
understanding atmospheric aerosol chemistry and its connections to climate.
Advances in technology for characterizing aerosol chemical composition and
physical properties have enabled rapid discovery in this area. This article
reviews fundamental concepts and recent developments surrounding ambient
aerosols, their chemical composition and sources, light-absorbing aerosols,
aerosols and cloud formation, and aerosol-based solar radiation management (also
known as solar geoengineering).
PMID- 28415857
TI - Sharing Data to Build a Medical Information Commons: From Bermuda to the Global
Alliance.
AB - The Human Genome Project modeled its open science ethos on nematode biology, most
famously through daily release of DNA sequence data based on the 1996 Bermuda
Principles. That open science philosophy persists, but daily, unfettered release
of data has had to adapt to constraints occasioned by the use of data from
individual people, broader use of data not only by scientists but also by
clinicians and individuals, the global reach of genomic applications and diverse
national privacy and research ethics laws, and the rising prominence of a diverse
commercial genomics sector. The Global Alliance for Genomics and Health was
established to enable the data sharing that is essential for making meaning of
genomic variation. Data-sharing policies and practices will continue to evolve as
researchers, health professionals, and individuals strive to construct a global
medical and scientific information commons.
PMID- 28415862
TI - Multivariate Analysis and Statistics in Pharmaceutical Process Research and
Development.
AB - The application of statistics in pharmaceutical process research and development
has evolved significantly over the past decades, motivated in part by the
introduction of the Quality by Design paradigm, a landmark change in regulatory
expectations for the level of scientific understanding associated with the
manufacturing process. Today, statistical methods are increasingly applied to
accelerate the characterization and optimization of new drugs created via
numerous unit operations well known to the chemical engineering discipline. We
offer here a review of the maturity in the implementation of design of experiment
techniques, the increased incorporation of latent variable methods in process and
material characterization, and the adoption of Bayesian methodology for process
risk assessment.
PMID- 28415863
TI - Thermophysical Properties and Phase Behavior of Fluids for Application in Carbon
Capture and Storage Processes.
AB - Phase behavior and thermophysical properties of mixtures of carbon dioxide with
various other substances are very important for the design and operation of
carbon capture and storage (CCS) processes. The available empirical data are
reviewed, together with some models for the calculation of these properties. The
systems considered in detail are, first, mixtures of carbon dioxide, water, and
salts; second, carbon dioxide-rich nonelectrolyte mixtures; and third, mixtures
of carbon dioxide with water and amines. The empirical data and the plethora of
available models permit the estimation of key fluid properties required in the
design and operation of CCS processes. The engineering community would benefit
from the further development, and delivery in convenient form, of a small number
of these models sufficient to encompass the component slate and operating
conditions of CCS processes.
PMID- 28415864
TI - [Extrahepatic manifestations in chronic hepatitis C infected patients].
AB - The importance of chronic hepatitis C infection is significant. 3% of the World's
population is infected. There is at least one extrahepatic manifestation in 50%
of HCV patients, which makes the prognosis and mortality worse. The
pathomechanisms included are cryoglobulin production, immunmechanisms, and direct
viral effects. The authors summarize the main extrahepatic manifestations, as
well as treatment possibilities. The aim is to draw attention to this colourful
infection in order to improve the recognition in the era of the new effective
direct antiviral agents. Orv. Hetil., 2017, 158(16), 603-612.
PMID- 28415867
TI - [Supporting Semmelweis in French in 1849 in Strasbourg - the unfairly forgotten
Friedrich Wieger (1821-1890)].
PMID- 28415865
TI - [Placental gene activity of significant angiogenetic factors in the background of
intrauterine growth restriction].
AB - Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene
are both overexpressed in placental samples obtained from pregnancies with
intrauterine growth restriction compared to normal pregnancies. In the background
of these changes a mechanism can be supposed, in which the increased endoglin
activity in intrauterine growth restriction (IUGR) leads to impaired placental
circulation through an antioangiogenetic effect. This results in the development
of placental vascular dysfunction and chronic fetal hypoxia. It is chronic
hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal
vascular blood supply by promoting placental blood vessel formation. Although the
maternal serum placental growth factor (PlGF) level is a potential predictor for
both IUGR and praeeclampsia, placental PlGF gene activity may be less of an
active in the regulation of placental circulation in IUGR pregnancies during the
later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.
PMID- 28415868
TI - [Epidemiological data of Hungarian skiers' and snowboarders' medical problems].
AB - INTRODUCTION AND AIM: There are no high mountains or any advantageous
circumstances for winter sports in Hungary, yet within the 10 million population
there are about half a million people (the exact number is 550,000) who tend to
go for skiing or snowboarding abroad. Authors compared the injury statistical
data with results described in the international literature in order to develop
conclusions about the differences in the injury patterns and frequency between
the Hungarian ones' and those found in countries with plenty of winter sport
possibilities. METHOD: Authors analysed the winter sport injury cases of an
insurance company. All the injury happened abroad and the assistance provider of
the insurance company has managed the patient treatment and repatriation. Three
winter seasons (12 months) data was analysed from the point of view of injuries
frequency at different body parts and areas. Due to the fact that only limited
information was available a simple statistical method was applied. RESULTS: Of
222 cases 90.5% were ski-related injury and 8.6% were snowboard injury. As for
the skiers, the upper limb injuries accounted for 21.9%, the truncal region for
24.4% and the lower limb for 55.8%. Among snowboarders the upper limb injuries
accounted for 36.9%, the truncal region for 37% and the lower limb for 26.1%. The
most frequent was the knee (36.8%), the wrist (12.4) and the shoulder (11.4)
injury. Skier's thumb injury was only 1.5%. The most common snowboard injury was
the wrist trauma (31.6%), the head/neck/face was accounted 15.8% of all the
injuries. And the ankle was injured in 10.5% of all the cases. The head/neck and
the knee injury often combined with injuries of some other body part. 29 patients
(13%) had to be repatriated, the most frequent reason for the repatriation was
the injury of the lower limb. CONCLUSIONS: The Hungarian sportsmen's injury
patterns do not always follow data described in the international literature, but
they correspond to data of countries with similar geographical situation. The
injury rate of knee and of the shoulder displays same data, the injury rate of
the wrist was more frequent than in the international data, and this is true both
for skiers and the snowboarders. The Hungarians' injury of the truncal region
(mainly the head) was more frequent, but on the other hand the general injury
rate of other body parts proved to be a lower number. It seems that the frequent
use of the protective equipment and the preventive measures applied by the
Hungarians are mirrored in the lower injury figures. Orv. Hetil., 2017, 158(16),
618-624.
PMID- 28415869
TI - [Types of conflicts and conflict management among Hungarian healthcare workers].
AB - INTRODUCTION: Efficient communication, conflict management and cooperation are
the key factors of a successful patient care. AIM: This study is part of an
international comparative research. The aim of this study is to unfold conflicts
among healthcare workers. METHOD: 73 healthcare workers were interviewed using a
standardized interview protocol. The in-person interviews used the critical
incident method. 30 interviews (15 doctors, 15 nurses) were analysed with the
Atlas.ti 7 content analysis software. The sources, types, effects of conflicts
and conflict management strategies were investigated. RESULTS: The content
analysis unfolded the specificities of conflicts in healthcare based on personal
experiences. Organizational hierarchy was a substantial source of conflict,
especially among physicians, which originates from implicit rules. As a result of
the avoiding conflict management the conflicts remain partly unresolved which has
negative individual and group effect. CONCLUSIONS: Our conceptual framework helps
to develop a proper intervention specific to healthcare. Orv. Hetil., 2017,
158(16), 625-632.
PMID- 28415870
TI - Longitudinal changes in the antecedent and early manifest course of bipolar
disorder-A narrative review of prospective studies.
AB - OBJECTIVE: Prospective study designs ideally allow patients to be followed from
the first manifestations of the illness or even from an at-risk stage. It can
thus provide data on the predictive value of changes in clinical symptomatology,
cognition or further biological markers to broaden our understanding of the
etiopathology and symptomatic trajectory of bipolar disorders. The scope of this
narrative review is to summarize evidence from prospectively collected data on
psychopathological and other clinical and biological changes in the early
developmental course of bipolar disorders. METHODS: The narrative review was
based on a literature search conducted in February 2016 within the PubMed library
for prospective study data of persons in antecedent and early manifest stages of
manifest bipolar disorder published within the last 15 years. RESULTS: A total of
19 prospective studies were included. Regarding psychopathological features;
personality, temperament and character traits as well as changes in sleep and
circadian rhythm, the evidence suggests that risk factors for the development of
bipolar disorder can already be described and should be studied further to
understand their interaction, mediation with other factors and timing in the
developmental process of bipolar disorder. Apart from the positive family
history, childhood anxiety, sleep problems, subthreshold (hypo)manic symptoms and
certain character traits/emotionality should be identified and monitored already
in clinical practice as their presence likely increases risk of bipolar disorder.
Up to date no substantiated evidence was found from prospective studies
addressing cognitive features, life events, immunological parameters and
morphological central nervous system changes as potential risk factors for
bipolar disorder. CONCLUSION: For an improved understanding of episodic
disorders, longitudinal data collection is essential. Since the etiology of
bipolar disorders is complex, a number of potential risk factors have been
proposed. Prospective studies addressing this spectrum and resilience factors are
critical and will be best conducted within multi-site research networks or
initiatives.
PMID- 28415871
TI - Back to the future: Schizophrenia in retrospect and prospect.
PMID- 28415872
TI - Taking a look into the future: Do clinical and neurobiological trajectories tell
us more than what we already know?
PMID- 28415873
TI - Structural brain changes in schizophrenia at different stages of the illness: A
selective review of longitudinal magnetic resonance imaging studies.
AB - OBJECTIVE: Schizophrenia is a devastating mental disorder accompanied by aberrant
structural brain connectivity. The question whether schizophrenia is a
progressive brain disorder is yet to be resolved. Thus, it is not clear when
these structural alterations occur and how they develop over time. METHODS: In
our selective review, we summarized recent findings from longitudinal magnetic
resonance imaging studies investigating structural brain alterations and its
impact on clinical outcome at different stages of the illness: (1) subjects at
ultra-high risk of developing psychosis, (2) patients with a first episode
psychosis, and (3) chronically ill patients. Moreover, we reviewed studies
examining the longitudinal effects of medication on brain structure in patients
with schizophrenia. RESULTS: (1) Studies from pre-clinical stages to conversion
showed a more pronounced cortical gray matter loss (i.e. superior temporal and
inferior frontal regions) in those individuals who later made transition to
psychosis. (2) Studies investigating patients with a first episode psychosis
revealed a decline in multiple gray matter regions (i.e. frontal regions and
thalamus) over time as well as progressive cortical thinning in the superior and
inferior frontal cortex. (3) Studies focusing on patients with chronic
schizophrenia showed that gray matter decreased to a greater extent (i.e. frontal
and temporal areas, thalamus, and cingulate cortices)-especially in poor-outcome
patients. Very few studies reported effects on white matter microstructure in the
longitudinal course of the illness. CONCLUSION: There is adequate evidence to
suggest that schizophrenia is associated with progressive gray matter
abnormalities particularly during the initial stages of illness. However, causal
relationships between structural changes and illness course-especially in
chronically ill patients-should be interpreted with caution. Findings might be
confounded by longer periods of treatment and higher doses of antipsychotics or
epiphenomena related to the illness.
PMID- 28415874
TI - Making Early Intervention more equitable.
PMID- 28415875
TI - The ideal mood stabiliser: A quest for nirvana?
PMID- 28415876
TI - Phenomenal Insights: Extraordinary auditory hallucinations-Thought sonorisation.
PMID- 28415877
TI - The portrayal of psychiatry in popular culture: Harmful or helpful?
PMID- 28415878
TI - Predicting bipolar disorder: Vitally important, clinically difficult.
PMID- 28415879
TI - Depressive symptom trajectories in late adolescence and early adulthood: A
systematic review.
AB - OBJECTIVE: In adolescents and young adults, depressive symptoms are highly
prevalent and dynamic. For clinicians, it is difficult to determine whether a
young person reporting depressive symptoms is at risk of developing ongoing mood
difficulties or whether symptoms form part of a transient maturational process.
Trajectory analyses of longitudinally assessed symptoms in large cohorts have the
potential to untangle clinical heterogeneity by determining subgroups or classes
of symptom course and their risk factors, by interrogating the impact of known or
suspected risk factors on trajectory slope and intercept and by tracing the
interrelation between depressive symptoms and other clinical outcomes over time.
METHOD: We conducted a systematic review of trajectory studies conducted in
cohorts including people aged between 15 and 25 years. RESULTS: We retrieved 47
relevant articles. These studies suggest that young people fall into common mood
trajectory classes and that class membership and symptom course are mediated by
biological and environmental risk factors. Furthermore, studies provide evidence
that high and persistent depressive symptoms are associated with a range of
concurrent health and behavioral outcomes. CONCLUSION: Findings could assist in
the formulation of novel concepts of depressive disorders in young people and
inform preventive strategies and predictive models for clinical practice.
PMID- 28415880
TI - Introductory paragraph.
PMID- 28415881
TI - Hip and pelvic fracture patients with fear of falling: development and
description of the "Step by Step" treatment protocol.
AB - OBJECTIVE: Based on a theoretical framework and sound evidence, this article
describes a rehabilitation programme for patients with fear of falling after hip
and pelvic fracture. RATIONALE: Based on exercise science principles, current
knowledge from fall prevention, emotion regulation, and the Health Action Process
Approach we developed a theoretical framework, from which the components of the
intervention were derived. Description of the intervention: The intervention
consists of 6 components: (1) relaxation, (2) meaningful activities and mobility
based goals, (3) falls related cognitions and emotions, coping with high risk
tasks and situations, (4) individual exercise programme, (5) planning and
implementing exercises and activities, and (6) fall risks and hazards. The
intervention comprises of 8 individual sessions during 3 to 5 weeks of inpatient
rehabilitation and 4 telephone calls and 1 home visit over a 2-month post
discharge period. Each session or telephone call takes about 30-60 minutes. It is
provided to geriatric hip and pelvic fracture patients with concerns about
falling and no cognitive impairment. To ensure completeness of reporting, the
Template for Intervention Description and Replication (TIDierR) is used. RESULTS:
Fifty-seven patients were assigned to the intervention group. All 46 completers
met all pre-defined criteria for an intervention per protocol. CONCLUSION: The
programme is feasible to administer. We have completed a randomised controlled
trial, which will be submitted in due time (for trial protocol: www.isrctn.org ;
ISRCTN79191813).
PMID- 28415882
TI - RAGE receptor targeted bioconjuguate lipid nanoparticles of diallyl disulfide for
improved apoptotic activity in triple negative breast cancer: in vitro studies.
AB - In the present study, we have demonstrated receptor for advanced glycation
endproducts (RAGE) as a target for delivery of drugs specifically to triple
negative breast cancer cells. We have prepared solid lipid nanoparticle
formulation of cytotoxic agent di-allyl-disulfide (DADS) to overcome its
bioavailability issues. Then, we have surface modified DADS-loaded solid lipid
nanoparticles (DADS-SLN) with RAGE antibody to achieve site-specific delivery of
DADS to TNBC cells. We found a significant cellular internalization of RAGE
surface modified DADS-SLN (DADS-RAGE-SLN) when compared to DADS-SLN. The
cytotoxic effect of DADS was also significantly improved with DADS-RAGE-SLN by
downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as
observed by western blot analysis. RAGE-targeted delivery of cytotoxic agents can
be, therefore, a promising approach for improving antitumour activity and
reducing off-target effects.
PMID- 28415883
TI - Electrosteric stealth Rivastigmine loaded liposomes for brain targeting:
preparation, characterization, ex vivo, bio-distribution and in vivo
pharmacokinetic studies.
AB - Being one of the highly effective drugs in treatment of Alzheimer's disease,
Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion
of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin,
Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A
major challenge during the preparation of liposomes is maintaining a stable
formulation, therefore the aim of our study was to increase liposomal stability
by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase
stability by steric hindrance, yielding what we called an electrosteric stealth
(ESS) liposomes. A medium nano-sized liposome (478 +/- 4.94 nm) with a nearly
neutral zeta potential (ZP, -8 +/- 0.2 mV) and an entrapment efficiency
percentage of 48 +/- 6.22 was prepared. Stability studies showed no major
alteration after three months storage period concerning particle size,
polydispersity index, ZP, entrapment efficiency and in vitro release study
confirming the successful formation of a stable liposomes. No histopathological
alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS
liposomes showed higher % of drug permeating through the sheep nasal mucosa
(48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic
studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma
levels of the formula ESS compared to that of RHT intranasal solution and 486%
relative bioavailability of the mean brain levels.
PMID- 28415884
TI - Alcohol quantification: recent insights into amperometric enzyme biosensors.
AB - Biosensors are the switching channels that make sense. The biosensors have found
an empirical role in health applications (e.g. clinical diagnostics) as they
represent the technological counterpart of living senses. On a global scale,
alcohol analysis is indispensable for criminal justice systems, monitoring
medical conditions of HIV patients & pregnant women as well as public safety
issues regarding pilots, metro drivers, doctors etc. For addressing the clinical
and toxicological problems, much advancement in the improvement of biosensors
have been witnessed in recent decades. Currently, electrochemical biosensors
dominate the field which harnesses the synergistic action of enzymes and
nanomaterials for the analysis of ethanol. The enzymatic biosensors are the most
explored biosensing devices among all the types of biosensors, and employment of
nanomaterials has paved a way to the further improvements in this gem of a
discovery. The relative comparison to precise the alcohol biosensors has been
aptly discussed in the review on the basis of several analytical properties
including fabrication, linearity, sensitivity, response time, detection limit as
well as storage stability. Finally, the recent trends and emerging future
prospects of alcohol biosensors have been reviewed.
PMID- 28415885
TI - Fatigue and pain limit independent mobility and physiotherapy after hip fracture
surgery.
AB - PURPOSE: The patient's ability to complete their planned physiotherapy session
after hip fracture surgery has been proposed as an independent predictor for
achieving basic mobility independency upon hospital discharge. However, knowledge
of factors limiting mobility is sparse. We therefore examined patient reported
factors limiting ability to complete planned physiotherapy sessions as well as
limitations for not achieving independency in basic mobility early after hip
fracture surgery. METHODS: A total of 204 consecutive patients with a hip
fracture (mean (SD) age of 80 (9.9) years, 47 patients were admitted from a
nursing home) were treated in accordance with a multimodal program. The Cumulated
Ambulation Score was used to evaluate the patient's independency in three basic
mobility activities: getting in and out of bed, sit-to-stand-to-sit from a chair
and indoor walking. Pre-defined limitations; pain, motor blockade, dizziness,
fatigue, nausea, acute cognitive dysfunction and "other limitations", for not
achieving a full Cumulated Ambulation Score or inability to complete planned
physiotherapy sessions were noted by the physiotherapist on each of the three
first postoperative days. This period was chosen, because of its importance on
how well the patients had regained their pre-fracture functional level. RESULTS:
Fatigue and hip fracture-related pain were the most frequent reasons for patients
not achieving an independent basic mobility level (> 85%) or not fully completing
their planned physiotherapy (> 42%) on all three days. At hospital discharge
(median day 10), only 54% of the patients had regained their pre-fracture basic
mobility level. CONCLUSION: Based on the patient's perception, fatigue and pain
are the most frequent limitations in not achieving independent basic mobility and
not completing physiotherapy after hip fracture surgery. This raises questions
whether multimodal peri-operative programs can be further optimized to enhance
the early recovery of these frail patients. Implications for rehabilitation Early
postoperative mobilization is essential for patients undergoing hip fracture
surgery to regain the pre-fracture functional level, in not only the short but
also in the long term. The most frequent reasons for not achieving an independent
Cumulated Ambulation Score or completing physiotherapy, early after hip fracture
surgery, are fatigue, pain, and the habitual cognitive status of patients.
Knowledge concerning postoperative fatigue is important for rehabilitation
professionals and should contribute as an essential factor when planning
physiotherapy.
PMID- 28415886
TI - Post-operative delayed ambulation after thymectomy is associated withpre
operative six-minute walk distance.
AB - OBJECTIVE: Delayed post-operative ambulation is a risk of post-operative
complications and increases overall healthcare costs. We investigated pre
operative and intraoperative variables associated with delayed ambulation in
patients who underwent thymectomy. METHODS: A total of 57 consecutive patients
undergoing thymectomy were included in this study. Pre-operative functional
exercise capacity was evaluated by six-minute walk distance. Ambulation was
considered to be delayed if the patient could not walk the ward on post-operative
day 1. Binary logistic regression analysis was performed to clarify the factors
associated with delayed ambulation. RESULTS: Pre-operative six-minute walk
distance was the only significant variable that was associated with delayed
ambulation. The area under the receiver operating characteristic curve for
predicting delayed ambulation was 0.684 (95% confidential interval: 0.546-0.823,
p = 0.017), and the optimal discriminatory pre-operative six-minute walk distance
value was 498 m. Post-operative hospital stay was significantly longer in
patients with low six-minute walk distance (<498 m) than those with high six
minute walk distance (>=498 m). In contrast, the presence of myasthenia gravis or
adjuvant chemoradiotherapy was not associated with delayed ambulation.
CONCLUSIONS: Our results suggest that low pre-operative six-minute walk distance
is associated with delayed post-operative ambulation and longer post-operative
hospital stay in patients who underwent thymectomy. Implications for
rehabilitation The predictors for delayed ambulation after thymectomy are not
fully investigated. The presence of myasthenia gravis was not associated with
delayed ambulation. Low pre-operative six-minute walk distance was associated
with delayed ambulation.
PMID- 28415887
TI - Amelioration of late-onset hepatic steatosis in IDH2-deficient mice.
AB - Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general
population and can evolve into nonalcoholic steatohepatosis (NASH), cirrhosis,
and complications such as liver failure and hepatocellular carcinoma. Recently,
we reported that mitochondrial NADP+-dependent isocitrate dehydrogenase, encoded
by the IDH2, plays an important role in the regulation of redox balance and
oxidative stress levels, which are tightly associated with intermediary
metabolism and energy production. In the present study, we showed that in mice
targeted disruption of IDH2 attenuates age-associated hepatic steatosis by the
activation of p38/cJun NH2-terminal kinase (JNK) and p53, presumably induced by
the elevation of mitochondrial reactive oxygen species (ROS), which in turn
resulted in the suppression of hepatic lipogenesis and inflammation via the
upregulation of fibroblast growth factor 21 (FGF21) and the inhibition of
NFkappaB signaling pathways. Our finding uncovers a new mechanism involved in
hepatocellular steatosis and IDH2 may be a valuable therapeutic target for the
management of NAFLD.
PMID- 28415889
TI - Looking beyond the individual: Quality research requires supportive environments.
PMID- 28415888
TI - Bioengineered gold nanoparticles targeted to mesenchymal cells from patients with
bronchiolitis obliterans syndrome does not rise the inflammatory response and can
be safely inhaled by rodents.
AB - The use of gold nanoparticles (GNPs) as drug delivery system represents a
promising issue for diseases without effective pharmacological treatment due to
insufficient local drug accumulation and excessive systemic toxicity.
Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic
lung allograft dysfunction, the main challenge to long-term lung transplantation.
It is believed that due to repeated insults to epithelial bronchiolar cells local
inflammatory response creates a milieu that favors epithelial-mesenchymal
transition and activation of local mesenchymal cells (MCs) leading to airway
fibro-obliteration. In a previous work, we engineered GNPs loaded with the
mammalian target of rapamycin inhibitor everolimus, specifically decorated with
an antibody against CD44, a surface receptor expressed by primary MCs isolated
from bronchoalveolar lavage of BOS patients. We proved in vitro that these GNPs
(GNP-HCe) were able to specifically inhibit primary MCs without affecting the
bronchial epithelial cell. In the present work, we investigated the effect of
these bioengineered nanoconstructs on inflammatory cells, given that a
stimulating effect on macrophages, neutrophils or lymphocytes is strongly
unwanted in graft airways since it would foster fibrogenesis. In addition, we
administered GNP-HCe by the inhalatory route to normal mice for a preliminary
assessment of their pulmonary and peripheral (liver, spleen and kidney) uptake.
By these experiments, an evaluation of tissue toxicity was also performed. The
present study proves that our bioengineered nanotools do not rise an inflammatory
response and, under the tested inhalatory conditions that were used, are non
toxic.
PMID- 28415890
TI - Correction to: Deep genealogical analysis of a large cohort of participants in
the CARTaGENE project (Quebec, Canada).
PMID- 28415891
TI - Influence of two-electrode montages on the level-specific (LS) CE-Chirp auditory
brainstem response (ABR) at multiple intensity levels.
AB - OBJECTIVE: To investigate the influence of two different electrode montages
(ipsilateral: reference to mastoid and vertical: reference to nape of neck) to
the ABR results recorded using a level-specific (LS)-CE-Chirp(r) in normally
hearing subjects at multiple intensities levels. DESIGN: Quasi-experimental and
repeated measure study designs were applied in this study. Two different stopping
criteria were used, (1) a fixed-signal averaging 4000 sweeps and, (2) a minimum
quality indicator of Fmp = 3.1 with a minimum of 800 sweeps. STUDY SAMPLE: Twenty
nine normally hearing adults (18 females, 11 male) participated. RESULTS: Wave V
amplitudes were significantly larger in the LS CE-Chirp(r) recorded from the
vertical montage than the ipsilateral montage. Waves I and III amplitudes were
significantly larger from the ipsilateral LS CE-Chirp(r) than from the other
montages and stimulus combinations. The differences in the quality of the ABR
recording between the vertical and ipsilateral montages were marginal.
CONCLUSIONS: Overall, the result suggested that the vertical LS CE-Chirp(r) ABR
had a high potential for a threshold-seeking application, because it produced a
higher wave V amplitude. The Ipsilateral LS CE-Chirp(r) ABR, on the other hand,
might also have a high potential for the site of lesion application, because it
produced larger waves I and III amplitudes.
PMID- 28415892
TI - Intellectual streaking: The value of teachers exposing minds (and hearts).
AB - As teachers we often ask learners to be vulnerable and yet present ourselves as
high status, knowledgeable experts, often with pre-prepared scripts. This paper
investigates the metaphoric notion of "intellectual streaking" - the nimble
exposure of a teacher's thought processes, dilemmas, or failures - as a way of
modeling both reflection-in-action and resilience. While there is a tension
between credibility and vulnerability, both of which are necessary for trust, we
argue that taking a few risks and revealing deficits in knowledge or performance
can be illuminating and valuable for all parties.
PMID- 28415893
TI - REM sleep deprivation impairs muscle regeneration in rats.
AB - INTRODUCTION: The aim was observe the influence of sleep deprivation (SD) and
sleep recovery on muscle regeneration process in rats submitted to cryolesion.
METHODS: Thirty-two Wistar rats were randomly allocated in four groups: control
(CTL), SD for 96 h (SD96), control plus sleep recovery period (CTL + R) and SD96h
plus 96 h of sleep recovery (SD96 + R). The animals were submitted to muscle
injury by cryolesioning, after to SD and sleep recovery. RESULTS: The major
outcomes of this study were the reduction of muscular IGF-1 in both legs (injured
and uninjured) and a delay in muscle regeneration process of animals submitted to
SD compared to animals that slept, with increase connective tissue, inflammatory
infiltrate and minor muscle fibers. CONCLUSIONS: SD impairs muscle regeneration
in rats, moreover reduces muscular IGF-1 and sleep recovery was able to restore
it to basal levels, but it was not enough to normalize the muscle regeneration.
PMID- 28415894
TI - Should patients be optimistic about surgery? Resolving a conflicted literature.
AB - Following surgery, some patients suffer distress, disappointment, regret, poor
adjustment, and poor quality-of-life. Surgeons may define 'success' based on
objective clinical outcomes, but patients' perceptions of surgical success rely
primarily on a comparison to their initial expectations. We review the literature
on the relationship between patients' surgical expectations and psychosocial
outcomes and attempt to resolve a conflict in the literature. Specifically, we
propose that conflicting conclusions regarding the merits of optimism primarily
stem from differing methodological approaches by researchers in the field.
Studies that examine preoperative expectations in isolation typically conclude
that optimism is positively associated with beneficial psychosocial outcomes.
Studies that compare preoperative expectations to objective surgical outcomes
typically conclude that optimism, particularly unrealistic optimism, is
associated with detrimental psychosocial outcomes. As a whole, the evidence
strongly supports an association between optimistic expectations and positive
psychosocial outcomes following surgery if those expectations are based in
reality. If preoperative optimism ultimately turns out to be unrealistic,
however, it is likely to be a postoperative liability.
PMID- 28415895
TI - The value of liquid biopsy in diagnosis and monitoring of diffuse large b-cell
lymphoma: recent developments and future potential.
AB - INTRODUCTION: Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous
subset of non-Hodgkin lymphomas (NHL) that demonstrate many molecular alterations
and somatic mutations, all of which are targets for the recent development of
biomarkers that use various molecular biological techniques. These non-invasive
emerging biomarkers will be used in the next few years to better monitor the
response to immunochemotherapeutic treatments with the aim of completely
eradicating the disease in order to cure it. Areas covered: In this review, the
authors conducted a literature search to identify and summarize the major
advances in liquid biopsy techniques for DLBCL that are useful for diagnosis and
monitoring minimal residual disease (MRD). The authors report on the major
technological leaps represented by the main MRD tools (sequencing of clone
specific rearrangements of immunoglobulin genes and sequencing of somatic
mutations in circulating tumor plasma DNA) and present the expected future
developments and the impact of these new tools on clinical practice. Expert
commentary: The monitoring of somatic mutations in tumor plasma cell-free DNA
represents a promising tool for liquid biopsy, which will in the future allow non
invasive monitoring that will be used at any time to follow the response to the
treatment.
PMID- 28415896
TI - Multiple mini interviews (MMI): A perspective on the first year of MMI at
Brighton and Sussex Medical School.
AB - Since it was developed at McMaster University School of Medicine in 2002,
multiple medical interviews (MMI) have become a popular and accepted method of
assessing candidates applying for medical training. Unlike a traditional panel
interview it resembles the objective structured clinical examination (OSCE) with
numerous 8-10 min stations assessing different topics or scenarios pertinent to
medical training and healthcare. This was the first year of implementing MMI at
Brighton and Sussex Medical School and my first year of interviewing. I found the
process engaging and thought provoking.
PMID- 28415897
TI - Electric field-navigated transcranial magnetic stimulation for chronic tinnitus:
a randomized, placebo-controlled study.
AB - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may alleviate
tinnitus. We evaluated effects of electric field (E-field) navigated rTMS
targeted according to tinnitus pitch. No controlled studies have investigated
anatomically accurate E-field-rTMS for tinnitus. DESIGN: Effects of E-field-rTMS
were evaluated in a prospective randomised placebo-controlled 6-month follow-up
study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo
targeted to the left auditory cortex corresponding to tonotopic representation of
tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3
and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100)
for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap
Inventory (THI). STUDY SAMPLE: Thirty-nine patients (mean age 50.3 years).
RESULTS: The mean tinnitus intensity (F3 = 15.7, p < 0.0001), annoyance (F3 =
8.8, p = 0.0002), distress (F3 = 9.1, p = 0.0002) and THI scores (F4 = 13.8, p <
0.0001) decreased in both groups over time with non-significant differences
between the groups. After active rTMS, 42% and 37% of the patients showed
excellent response at 1 and 3 months against 15% and 10% in the placebo group (p
= 0.082 and p = 0.065). CONCLUSIONS: Despite the significant effects of rTMS on
tinnitus, differences between active and placebo groups remained non-significant,
due to large placebo-effect and wide inter-individual variation.
PMID- 28415899
TI - Specific muscle synergies in national elite female ice hockey players in response
to unexpected external perturbation.
AB - This study aimed to investigate specific muscle synergies in elite ice hockey
players indicating highly developed postural control strategies used to restore
balance against unexpected external perturbations. Seven elite athletes (EA) on
the women's national ice hockey team and 7 non-athletes (NA) participated in this
study. Based on trajectories of centre of mass (COM), analysis periods were
divided into an initial phase (a balance disturbance after perturbation onset)
and a reversal phase (a balance recovery response), respectively. Muscle
synergies were extracted at each phase by using non-negative matrix
factorization. k-means cluster analysis was performed to arrange similar muscle
synergies in all participants. EA showed significantly shorter recovery period of
COM and smaller body sway than NA. In the initial phase, we identified 2 EA
specific synergies related to ankle plantar flexors or neck extensors. In the
case of an NA-specific synergy, co-activation of the ankle plantar flexors and
dorsiflexors was found. In the reversal phase, no specific muscle synergies were
identified. As the results, EA-specific muscle synergies showed low co-activation
strategy of agonists and antagonists in ankle and neck extensors. Our results
could provide critical information for rehabilitation strategies in athletes
requiring high postural stability.
PMID- 28415898
TI - 31Phosphorus magnetic resonance spectroscopy of the liver for evaluating
inflammation and fibrosis in autoimmune hepatitis.
AB - BACKGROUND: Liver biopsy is the gold standard in evaluating inflammation and
fibrosis in autoimmune hepatitis. AIMS: In search of non-invasive follow-up tools
in autoimmune hepatitis, we evaluated 31phosphorus magnetic resonance
spectroscopy (31P MRS). METHODS: Twelve consecutive AIH patients (mean age 42.8
years, 10 women) underwent liver biopsy, routine laboratory liver function tests,
which were compared to findings in 31P MRS and transient elastography (TE).
RESULTS: Phosphoenolpuryvate (PEP) correlated with the grade of inflammation (r =
0.746, p = .005) and thromboplastin time (r = 0.592, p = .043). It also
differentiated patients with active inflammation from patients without (t =
3.781, p = .009). There was no correlation between PEP and aminotransferase or
immunoglobulin G levels. The phosphoethanolamine (PE)/phosphocholine (PC) ratio,
PE/glyserophosphoethanolamine (GPE) ratio and PC/[total phosphomonoester (PME) +
phosphodiester (PDE)] ratios correlated with immunoglobulin G (r = 0.764, p =
.006; r = 0.618, p = .043; and r= -0.636, p = .035, respectively). PME/PDE and
PE/GPE correlated with fibrosis (r = 0.668, p = .018 and r = 0.604, p = .037).
PE/GPE also differentiated F3 from F0-2 patients (t = 3.810, p = .003).
Phosphorus metabolites did not correlate with TE results and TE did not correlate
with liver histology or laboratory parameters. CONCLUSIONS: 31P MRS seems to
detect active inflammation and advanced fibrosis in AIH patients. TE was
ineffective in fibrosis quantification.
PMID- 28415900
TI - Pediatric nurse practitioners' clinical competencies and knowing patterns in
nursing: Focus group interviews.
AB - BACKGROUND: The generic competency domains of advanced nursing practice have been
reported on in numerous countries, but rather few studies have examined
competencies specific to pediatric nurse practitioners (PNPs). OBJECTIVES: We
identified the core clinical competencies of PNPs in South Korea and related
these identified competencies to the five patterns of knowing in nursing. DESIGN:
Focus group interviews were conducted with five PNP students and four PNPs using
two thematic questions, one on clinical competencies required for PNPs and the
other on competencies specific to Korean PNPs. A purposive sampling method was
used to choose nurses with varying work experience and age from different
hospital units. The inclusion criterion for PNP students was having at least two
years of clinical experience and that for PNPs was having at least two years of
clinical experience as a PNP in pediatric units in tertiary hospitals. The
verbatim transcriptions of these interviews were analysed by two researchers
using inductive content analysis. RESULTS: Six clinical competency domains were
identified including advanced pediatric-specific knowledge and clinical skills,
education and counseling, utilization and engagement in research, professional
identity development, clinical and professional leadership, and holistic care.
Some competencies identified were related to empirical and ethical knowledge that
could be taught in nursing, whereas others were based on esthetic and personal
knowledge, which can be mastered through professional experience. CONCLUSIONS: To
provide holistic care for children and families, PNPs must acquire all necessary
patterns of knowing through continuing education and individual reflection on
personal practice.
PMID- 28415901
TI - Sloping ABR baselines and the ECG myogenic artefact.
AB - OBJECTIVE: To investigate the possibility that a sloping baseline in an ABR
recording has its origins in cardiac activity and if so, identify how it is
expressed. DESIGN: The effect of ECG removal on the averaged ABR was investigated
at two artefact rejection levels. STUDY SAMPLE: Ten 1-minute records of raw EEG
containing ABR responses but contaminated with cardiac activity were recorded
from babies under 12 weeks of age and re-averaged using two artefact rejection
levels. The slope of the ABR recording was measured. The measurements were
repeated after removing effectively the cardiac activity from the records.
RESULTS: A sloping baseline was observed at one or both artefact rejection levels
in all records. The slope varied as the artefact rejection level was changed,
suggesting this may be implicated in slope generation. The slope effectively
disappeared when the cardiac activity was removed from the record. CONCLUSIONS:
Cardiac activity has the potential to cause a sloping ABR baseline. A possible
explanation for this effect is offered, together with suggestions for tester
strategy when a sloping ABR baseline is seen in a clinical setting.
PMID- 28415902
TI - Metabolism studies on hydroxygenkwanin and genkwanin in human liver microsomes by
UHPLC-Q-TOF-MS.
AB - Hydroxygenkwanin (HYGN) and genkwanin (GN) are major constituents of Genkwa Flos
for the treatment of edema, ascites, cough, asthma and cancer. This is a report
about the investigation of the metabolic fate of HYGN and GN in human liver
microsomes and the recombinant UDP-glucuronosyltransferase (UGT) enzymes by using
ultra-performance liquid chromatography quadrupole time-of-flight mass
spectrometry (UHPLC-Q-TOF-MS). An on-line data acquisition method multiple mass
defect filter (MMDF) combined with dynamic background subtraction (DBS) was
developed to trace all probable metabolites. Based on this analytical strategy,
three phase I metabolites and seven glucuronide conjugation metabolites of HYGN,
seven phase I metabolites and 12 glucuronide conjugation metabolites of GN were
identified in the incubation samples of human liver microsomes. The results
indicated that demethylation, hydroxylation and o-glucuronidation were main
metabolic pathways of HYGN and GN. The specific UGT enzymes responsible for HYGN
and GN glucuronidation metabolites were identified using recombinant UGT enzymes.
The results indicated that UGT1A1, UGT1A3, UGT1A9, UGT1A10 and UGT2B7 might play
major roles in the glucuronidation reactions. Overall, this study may be useful
for the investigation of metabolic mechanism of HYGN and GN, and it can provide
reference and evidence for further experiments.
PMID- 28415903
TI - The impact of emotion on numerical estimation: A developmental perspective.
AB - Recent literature has revealed underestimation effects in numerical judgments
when adult participants are presented with emotional stimuli (as opposed to
neutral). Whether these numerical biases emerge early in development however, or
instead reflect overt, learned responses to emotional stimuli across development
are unclear. Moreover, reported links between numerical acuity and mathematics
achievement point to the importance of exploring how numerical approximation
abilities in childhood may be influenced in real-world affective contexts. In
this study, children (aged 6-10 years) and adults were presented with happy and
neutral facial stimuli in the context of a numerical bisection task. Results
reveal that children, like adults, underestimate number following emotional
(i.e., happy) faces (relative to neutral). However, children's, but not adult's,
responses were also significantly more precise following emotional stimuli. In a
second experiment, adult judgments revealed a similar increase in precision
following emotional stimuli when numerical discriminations were more challenging
(involving larger sets). Together, results are the first to reveal children, like
adults, underestimate number in the context of emotional stimuli and this
underestimation bias is accompanied with enhanced response precision.
PMID- 28415904
TI - Wire Atrial Septostomy.
AB - Both balloon atrial septostomy and static balloon dilation are often ineffective
in creating a large atrial septal defect in patients with a thickened atrial
septum. In such situations, blade atrial septostomy and atrial septal stenting
are alternative treatments. We have devised and performed a new technique, called
wire atrial septostomy, which uses a thin soft wire to create a large defect. The
details of the procedure are presented.
PMID- 28415905
TI - Cardiac Perivascular Epithelioid Cell Tumor.
AB - Cardiac tumors presenting as mediastinal masses in childhood are rare. This
report describes the case of a 6-year-old girl who presented to us after a failed
attempt at resection of a mass arising from the left atrial appendage. Computed
tomography-guided biopsy suggested a perivascular epithelioid cell tumor
(PEComa). Sirolimus was started in order to reduce the mass size. She
subsequently underwent resection of the mass by midline sternotomy approach and
cardiopulmonary bypass. Recovery was uneventful and the child is doing well at
two-year follow-up. Contemporary literature is reviewed. Only seven cases,
including two children, with mediastinal PEComa have been reported. Pathology and
treatment options are discussed.
PMID- 28415906
TI - Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium
falciparum and on peritoneal cells of Swiss mice.
AB - CONTEXT: Plants of the Piperaceae family produce piplartine that was used to
synthesize the cinnamides. OBJECTIVE: To assess the effects of piplartine (1) and
cinnamides (2-5) against the protozoa responsible for malaria and leishmaniasis,
and peritoneal cells of Swiss mice. MATERIALS AND METHODS: Cultures of Leishmania
amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells
were incubated, in triplicate, with different concentrations of the compounds (0
to 256 MUg/mL). The inhibitory concentration (IC50) in L. amazonensis and
cytotoxic concentration (CC50) in peritoneal cell were assessed by the MTT method
after 6 h of incubation, while the IC50 for P. falciparum-infected erythrocytes
was determined by optical microscopy after 48 or 72 h of incubation; the
Selectivity Index (SI) was calculated by CC50/IC50. RESULTS: All compounds
inhibited the growth of microorganisms, being more effective against P.
falciparum after 72 h of incubation, especially for the compounds 1 (IC50 = 3.2
MUg/mL) and 5 (IC50 = 6.6 MUg/mL), than to L. amazonensis (compound 1 = 179.0
MUg/mL; compound 5 = 106.0 MUg/mL). Despite all compounds reducing the viability
of peritoneal cells, the SI were <10 to L. amazonensis, whereas in the cultures
of P. falciparum the SI >10 for the piplartine (>37.4) and cinnamides 4 (>10.7)
and 5 (= 38.4). DISCUSSION AND CONCLUSION: The potential of piplartine and
cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical
studies to evaluate their effects in murine malaria and to determine their
mechanisms in cells of the immune system.
PMID- 28415908
TI - The association of personal semantic memory to identity representations: insight
into higher-order networks of autobiographical contents.
AB - Identity representations are higher-order knowledge structures that organise
autobiographical memories on the basis of personality and role-based themes of
one's self-concept. In two experiments, the extent to which different types of
personal semantic content are reflected in these higher-order networks of
memories was investigated. Healthy, young adult participants generated identity
representations that varied in remoteness of formation and verbally reflected on
these themes in an open-ended narrative task. The narrative responses were scored
for retrieval of episodic, experience-near personal semantic and experience-far
(i.e., abstract) personal semantic contents. Results revealed that to reflect on
remotely formed identity representations, experience-far personal semantic
contents were retrieved more than experience-near personal semantic contents. In
contrast, to reflect on recently formed identity representations, experience-near
personal semantic contents were retrieved more than experience-far personal
semantic contents. Although episodic memory contents were retrieved less than
both personal semantic content types to reflect on remotely formed identity
representations, this content type was retrieved at a similar frequency as
experience-far personal semantic content to reflect on recently formed identity
representations. These findings indicate that the association of personal
semantic content to identity representations is robust and related to time since
acquisition of these knowledge structures.
PMID- 28415907
TI - Transdermal oxycodone patch for the treatment of postherpetic neuralgia: a
randomized, double-blind, controlled trial.
AB - AIM: To evaluate the efficacy, systemic exposure, safety and tolerability of a
transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM) in
patients with postherpetic neuralgia (PHN). PATIENTS & METHODS: The study was a
Phase IIa, multicenter, randomized, double-blind, vehicle-controlled crossover
study. RESULTS: While the TPM/oxycodone patch did not significantly improve
'average' Numeric Pain Rating Scale scores versus vehicle patch, patients
reporting high levels of paresthesia (n = 9) showed a trend toward improved pain
reduction. The TPM/oxycodone patch resulted in a low systemic exposure to
oxycodone and was well tolerated. CONCLUSION: The TPM/oxycodone patch delivered
oxycodone to the site of perceived pain in subjects suffering from PHN, but did
not provide analgesia for the broad PHN indication.
PMID- 28415909
TI - Detecting coached neuropsychological dysfunction: a simulation experiment
regarding mild traumatic brain injury.
AB - OBJECTIVE: Performance validity tests (PVTs) and symptom validity tests (SVTs)
are often administered during neuropsychological evaluations. Examinees may be
coached to avoid detection by measures of response validity. Relatively little
research has evaluated whether graduated levels of coaching has differential
effects upon PVT and SVT performance. Accordingly, the present experiment
evaluated the effect of graduated levels of coaching upon the classification
accuracy of commonly used PVTs and SVTs and the currently accepted criterion of
failing two or more PVTs or SVTs. METHOD: Participants simulated symptoms
associated with mild traumatic brain injury (TBI). One group was provided
superficial information concerning cognitive, emotional, and physical symptoms.
Another group was provided detailed information about such symptoms. A third
group was provided detailed information about symptoms and guidance how to evade
detection by PVTs. These groups were compared to an honest-responding group.
Extending prior experiments, stand-alone and embedded PVT measures were
administered in addition to SVTs. RESULTS: The three simulator groups were
readily identified by PVTs and SVTs, but a meaningful minority of those provided
test-taking strategies eluded detection. The Word Memory Test emerged as the most
sensitive indicator of simulated mild TBI symptoms. PVTs achieved more sensitive
detection of simulated head injury status than SVTs. CONCLUSIONS: Individuals
coached to modify test-taking performance were marginally more successful in
eluding detection by PVTs and SVTs than those coached with respect to TBI
symptoms only. When the criterion of failing two or more PVTs or SVTs was
applied, only 5% eluded detection.
PMID- 28415910
TI - Transfer of training in simple addition.
AB - In recent years, several researchers have proposed that skilled adults may solve
single-digit addition problems (e.g., 3 + 1 = 4, 4 + 3 = 7) using a fast counting
procedure. Practicing a procedure often leads to transfer of learning and faster
performance of unpracticed items. Such transfer has been demonstrated using a
counting-based alphabet arithmetic task (e.g., B + 4 = C D E F) that indicated
robust generalization of practice (i.e., response time [RT] gains) when untrained
transfer problems at test had been implicitly practiced (e.g., practice B + 3,
test B + 2 or B + 1). Here, we constructed analogous simple addition problems
(practice 4 + 3, test 4 + 2 or 4 + 1). In each of three experiments (total n =
108), participants received six practice blocks followed by two test blocks of
new problems to examine generalization effects. Practice of addition identity
rule problems (i.e., 0 + N = N) showed complete transfer of RT gains made
during practice to unpracticed items at test. In contrast, the addition ties (2 +
2, 3 + 3, etc.) presented large RT costs for unpracticed problems at test, but
sped up substantially in the second test block. This pattern is consistent with
item-specific strengthening of associative memory. The critical items were small
non-tie additions (sum <= 10) for which the test problems would be implicitly
practiced if counting was employed during practice. In all three experiments (and
collectively), there was no evidence of generalization for these items in the
first test block, but there was robust speed up when the items were repeated in
the second test block. Thus, there was no evidence of the generalization of
practice that would be expected if counting procedures mediated our participants'
performance on small non-tie addition problems.
PMID- 28415911
TI - Risk, safety and sex among male PrEP users: time for a new understanding.
AB - Recent advances in biomedical HIV prevention have led to optimistic projections
of a dramatic worldwide reduction of new infections by 2030. This optimism is
counterbalanced by concerns that the protective benefits of one such technology,
HIV pre-exposure prophylaxis (PrEP), may be negated by increases in other
behaviours that offset these benefits (risk compensation). To contribute to a
deeper understanding of concepts of safety and risk in the context of HIV PrEP,
we draw on the narrative accounts of 61 male PrEP users who participated in the
inaugural PrEP demonstration project: the iPrEx open-label extension study. We
conducted in-depth interviews with a purposeful sample of iPrEx participants.
Overall, participants did not report significant changes to their sexual
practices once they had begun taking PrEP. Rather, participants reported
experiencing a sense of relief or reprieve from HIV-related stress. This
unburdening of fear did not necessarily lead to condomless sex. Instead, men
expressed feeling a sense of security and less free-floating fear of HIV. We
contend that no longer living under the threat of HIV is a significant benefit
that has not been adequately explored in HIV prevention research.
PMID- 28415912
TI - A Method for the Immunohistochemical Identification and Localization of Osterix
in Periosteum-Wrapped Constructs for Tissue Engineering of Bone.
AB - A novel immunohistochemistry (IHC) approach has been developed to label and
localize osterix, a bone-specific transcription factor, within formalin-fixed,
paraffin-embedded, tissue-engineered constructs uniquely containing synthetic
polymers and human periosteal tissue. Generally, such specimens consisting in
part of polymeric materials and mineral are particularly difficult for IHC
identification of proteins. Samples here were fabricated from human periosteum,
electrospun poly-l-lactic acid (PLLA) nanofibers, and polycaprolactone/poly-l
lactic acid (PCL/PLLA, 75/25) scaffolds and harvested following 10 weeks of
implantation in athymic mice. Heat-induced and protease-induced epitope retrieval
methods from selected existing protocols were examined to identify osterix. All
such protease-induced techniques were unsuccessful. Heat-induced retrieval gave
positive results for osterix immunohistochemical staining in sodium
citrate/EDTA/Tween 20 with high heat (120C) and pressure (~30 psi) for 10 min,
but the heat and pressure levels resulted in tissue damage and section
delamination from slides that limited protocol effectiveness. Heat-induced
epitope retrieval led to other osterix-positive staining results achieved with
minimal impact on structural integrity of the tissue and polymers in sodium
citrate/EDTA/Tween 20 buffer at 60C and normal pressure (14.5 psi) for 72 hr. The
latter approach identified osterix-positive cells by IHC within periosteal
tissue, layers of electrospun PLLA nanofibers, and underlying PCL/PLLA scaffolds
of the tissue-engineered constructs.
PMID- 28415913
TI - Characteristics and management of primary and other immune thrombocytopenias:
Spanish registry study.
AB - BACKGROUND: The natural history and its modulation by treatments administered for
immune thrombocytopenia (ITP) in the clinical practice remains unknown. In
addition, little information is available on the characteristics and management
of ITP in Spain. METHODS: We conducted an observational, multicenter, registry in
70 Hematology Services from Spain between 2009 and 2011, which included children
from 2 months of age and adults with primary ITP or another ITP diagnosed within
the last 6 months (platelet count [PC] < 100 * 109/l). Patients were followed-up
at 6 and 12 months. RESULTS: 484 patients were included (median [Q1, Q3] age 52
[29,74] years, 87.6% adults), 56% women, 10.5% with secondary ITP. Median (Q1,
Q3) PC at diagnosis was 12 * 109/l (4, 32); 72% of patients had bleeding symptoms
(62% cutaneous bleeding, 29% oral cavity bleeding, 18% epistaxis). 81% of
patients with primary ITP received first-line treatment, mainly with
corticosteroids (>6 weeks in 59% of cases), either alone (41%) or associated with
intravenous immunoglobulin (33%). The response (>=30 * 109/L) to first-line
treatment was 92%. A total of 19% of patients received second-line treatment and
6% additional treatments. At 12 months, 74% of primary ITP patients maintained a
PC >= 100 * 109/L in absence of treatment (10% still had hemorrhagic
manifestations). CONCLUSIONS: Characteristics of Spanish ITP patients are
comparable to those from other countries. Although a high response rate to first
line treatments is observed, at 1 year, the disease persists in around one
quarter of patients. Overall therapeutic management in Spain conforms to current
recommendations, except for an excessive duration of corticosteroids therapy.
PMID- 28415914
TI - Sealing of the round and oval window niches with triamcinolone-soaked fascia as
salvage surgical therapy in sudden sensorineural hearing loss.
AB - CONCLUSIONS: Triamcinolone-soaked fascia seems to show better hearing improvement
when added to tympanotomy for sudden idiopathic sensorineural hearing loss
(SSHL), compared to fascia round window occlusion without triamcinolone.
OBJECTIVES: To analyse if adding triamcinolone to sealing the round and oval
window niches with fascia results in improved audiological outcome for acute
SNHL. METHODS: Fifty-three patients (27m:43 +/- 12 years, 26f:45 +/- 14 years)
with acute SSHL >=50dB over 3 frequencies, who failed primary therapy, underwent
transcanal tympanotomy. Twenty-five patients (Group A;cortisone:14m, 11f:46 +/- 9
years) received sealing of the round and oval window with fascia soaked in
triamcinolone (1ml; 40mg/ml) and 28 controls (Group B;no-cortisone:13m, 15f, 42
+/- 12 years) without triamcinolone. Frequency specific and pure tone average
(PTA =500-1000-2000-3000Hz) results were compared between Group A and B pre- and
postoperatively. RESULTS: In Group A the PTA improved by >=10dB in 21/25(83%)
cases; in Group B 18/28(63%). Group A showed a statistically significantly better
improvement across all frequencies, while linear regression revealed a
significant decrease of posttherapeutic PTA to 94.96% of the initial PTA (p =
.037). The overall PTA improved by 24dB. Group A improved from 73dB to 41dB(
32dB) PTA, Group B improved from 76dB to 56dB PTA (-20dB) (p < .05). Group A
showed a significant additional decrease of 12.8dB (p < .001).
PMID- 28415915
TI - Evaluation of dogs with macroscopic haematuria: a retrospective study of 162
cases (2003-2010).
AB - AIMS: To retrospectively describe clinical features of dogs that were presented
to a small animal clinic between 2003-10 with macroscopic haematuria, and
investigate whether signalment of the dog and severity and duration of the
haematuria at admission were associated with specific aetiologies. METHODS:
Medical records were evaluated of 162 dogs with macroscopic haematuria admitted
to a University-based small animal clinic in Thessaloniki, Greece, from January
2003 to December 2010. The inclusion criteria were discolouration of the urine
sediment combined with abnormal numbers of erythrocytes, when examined
microscopically. Data collected from the medical records included signalment,
severity, frequency and duration of haematuria, and diagnosis. RESULTS: Between
January 2007 and December 2010, 8,893 dogs were admitted to the clinic; of these
99 (1.1%) were admitted with haematuria. Of the 162 dogs with records of
haematuria, 80 (49.4%) were aged between 5.1-10 years, presented with acute
(96/162; 59.3%), constant (99/162; 61.1%) and mild/moderate (150/162; 92.6%)
haematuria. Of 147 dogs with a recorded diagnosis, the commonest diagnoses were
urinary tract infection (UTI, 42/147; 28.6%), urolithiasis (38/147; 25.9%),
prostatic disease (25/147; 17.0%) and urinary tumours (13/147; 8.8%). The
prevalence of UTI was higher in female (22/56; 39%) than male (20/91; 22%) dogs,
and in medium sized (22/52; 42%) than small (6/40; 15%) dogs. Urolithiasis was
most prevalent in small (21/40; 52.5%) dogs, and all dogs with urolithiasis
presented with mild/moderate haematuria. The prevalence of prostatic disease was
highest in large (11/46; 24%) and giant (3/9; 33%) sized dogs and in dogs aged
>10 years (8/30; 27%). CONCLUSIONS AND CLINICAL RELEVANCE: In this retrospective
study from one small animal clinic, UTI, urolithiasis, prostatic disease and
urinary tumours predominated among the causes of canine haematuria. The
consideration of sex, age, and size of the dog and characteristics of haematuria
were found to be useful parameters when forming the list of differential
diagnoses.
PMID- 28415916
TI - Association between psychosocial stress and hypertension: a systematic review and
meta-analysis.
AB - AIM: The etiology of hypertension is various and complex, involving both genetic
and behavioral factors. The relationship between psychosocial stress and
hypertension has been hypothesized. More and more people experience increased
anxiety, depression, and chronic psychosocial stress brought on by globalization,
cultural changes, socioeconomic changes, and stress at the work place. Although a
plethora of studies have investigated the interaction between psychosocial stress
and hypertension, this relationship is still contentious. The objective of this
study is twofold. First, a review of recent advancements in our understanding of
the relationship between psychosocial stress and hypertension. Second, a meta
analysis aiming to assess the relationship between chronic psychosocial stress
and blood pressure. METHODS: We systematically searched and identified relevant
studies from five databases, including PubMed, Cochrane Library, China National
Knowledge Infrastructure (CNKI), CQVIP, and the Wanfang Database until April
2016. Eleven studies encompassing 5696 participants were included in the final
analysis. RESULTS: Data showed that psychosocial stress was associated with an
increased risk of hypertension (OR = 2.40, 95% CI = 1.65-3.49), and hypertensive
patients had a higher incidence of psychosocial stress compared to normotension
patients (OR = 2.69, 95% CI = 2.32-3.11). Based on our meta-analysis, chronic
psychosocial stress may be a risk factor for hypertension. CONCLUSION: The few
cohort and case-control studies on the association between psychosocial stress
and hypertension employed variable definition of stressors and the responses,
making the meta-analysis difficult. Although we found an association between
chronic psychosocial stress and hypertension, more studies are needed to confirm
this relationship.
PMID- 28415917
TI - Exercise rehabilitation immediately following ischemic stroke exacerbates
inflammatory injury.
AB - OBJECTIVES: The rehabilitative benefits of physical exercise after stroke appear
to be contingent upon exercise initiation timing. The present study assessed the
hypothesis that very early post-stroke exercise would amplify cellular stress and
increases expression of pro-inflammatory mediators, while exercise initiated
later would limit the inflammation associated with cerebral ischemia/reperfusion
injury. METHODS: Adult rats were subjected to middle cerebral artery occlusion
and subsequently assigned to one of seven groups: one sham injury control group,
three stroke groups subjected to exercise initiated after 6, 24 hours, or 3 days
of reperfusion, and three stroke groups not subjected to exercise. Expression of
intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM
1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta)
were examined 3 and 24 hours after completion of exercise regimens (and at
corresponding time points in non-exercise controls). Heat shock protein-70
(Hsp70) and hypoxia inducible factor-1alpha (HIF-1alpha) expression levels were
also compared between exercise and non-exercise groups. RESULTS: Early post
stroke exercise was associated with increased expression of pro-inflammatory
mediators (ICAM-1, VCAM-1, TNF-alpha, and IL-1beta) and increased expression of
cell stress markers (Hsp70 and HIF-1alpha). Exercise initiated after 3 days of
reperfusion was associated with decreased expression of these molecules.
CONCLUSION: Post-stroke exercise, if too early, may result in elevated levels of
cell stress and increased expression of pro-inflammatory cytokines, which may
amplify the tissue damage associated with cerebral ischemia/reperfusion injury.
The results shed light on the manner in which exercise initiation timing may
affect post-stroke rehabilitation.
PMID- 28415918
TI - Financial Difficulty: A Barrier to Self-care in Patients With Diabetes.
PMID- 28415920
TI - What can the food and drink industry do to help achieve the 5% free sugars goal?
AB - AIMS: To contribute evidence and make recommendations to assist in achieving free
sugars reduction, with due consideration to the broader picture of weight
management and dietary quality. METHODS: An expert workshop in July 2016
addressed options outlined in the Public Health England report 'Sugar reduction:
The evidence for action' that related directly to the food industry. Panel
members contributed expertise in food technology, public heath nutrition,
marketing, communications, psychology and behaviour. Recommendations were
directed towards reformulation, reduced portion sizes, labelling and consumer
education. These were evaluated based on their feasibility, likely consumer
acceptability, efficacy and cost. RESULTS: The panel agreed that the 5% target
for energy from free sugars is unlikely to be achievable by the UK population in
the near future, but a gradual reduction from average current level of intake is
feasible. Progress requires collaborations between government, food industry, non
government organisations, health professionals, educators and consumers.
Reformulation should start with the main contributors of free sugars in the diet,
prioritising those products high in free sugars and relatively low in
micronutrients. There is most potential for replacing free sugars in beverages
using high-potency sweeteners and possibly via gradual reduction in sweetness
levels. However, reformulation alone, with its inherent practical difficulties,
will not achieve the desired reduction in free sugars. Food manufacturers and the
out-of-home sector can help consumers by providing smaller portions. Labelling of
free sugars would extend choice and encourage reformulation; however, government
needs to assist industry by addressing current analytical and regulatory
problems. There are also opportunities for multi-agency collaboration to develop
tools/communications based on the Eatwell Guide, to help consumers understand the
principles of a varied, healthy, balanced diet. CONCLUSION: Multiple strategies
will be required to achieve a reduction in free sugars intake to attain the 5%
energy target. The panel produced consensus statements with recommendations as to
how this might be achieved.
PMID- 28415921
TI - Intimate strangers: Eritrean male asylum seekers' perceptions of marriage and
sexuality.
AB - This study examined perceptions of marriage and sexuality among male asylum
seekers from Eritrea. Semi-structured in-depth interviews were conducted with 14
men living in Israel. Their perceptions of marriage and sexuality were found to
be influenced by their life as asylum seekers, and particularly by their
encounter with a different culture, by their lack of legal status, and by the
marked numerical imbalance between women and men within their community. Changes
in their perceptions occurred after their arrival in Israel, and included greater
relaxing of social codes and the transition from a relatively 'closed' sexual
mindset to a more 'open' one. It is important to understand how lack of status
affects male asylum seekers' intimate relationships with women, and to recognise
such men as subjects with legitimate sexual and partnering needs, thereby
broadening existing discourse in this field, which tends to present male asylum
seekers primarily as sources of cheap labour and as sexual Others.
PMID- 28415922
TI - Host pharmacokinetics and drug accumulation of anthelmintics within target
helminth parasites of ruminants.
AB - Anthelmintic drugs require effective concentrations to be attained at the site of
parasite location for a certain period to assure their efficacy. The processes of
absorption, distribution, metabolism and excretion (pharmacokinetic phase)
directly influence drug concentrations attained at the site of action and the
resultant pharmacological effect. The aim of the current review article was to
provide an overview of the relationship between the pharmacokinetic features of
different anthelmintic drugs, their availability in host tissues, accumulation
within target helminths and resulting therapeutic efficacy. It focuses on the
anthelmintics used in cattle and sheep for which published information on the
overall topic is available; benzimidazoles, macrocyclic lactones and monepantel.
Physicochemical properties, such as water solubility and dissolution rate,
determine the ability of anthelmintic compounds to accumulate in the target
parasites and consequently final clinical efficacy. The transcuticular absorption
process is the main route of penetration for different drugs in nematodes and
cestodes. However, oral ingestion is a main route of drug entry into adult liver
flukes. Among other factors, the route of administration may substantially affect
the pharmacokinetic behaviour of anthelmintic molecules and modify their
efficacy. Oral administration improves drug efficacy against nematodes located in
the gastroinestinal tract especially if parasites have a reduced susceptibility.
Partitioning of the drug between gastrointestinal contents, mucosal tissue and
the target parasite is important to enhance the drug exposure of the nematodes
located in the lumen of the abomasum and/or small intestine. On the other hand,
large inter-animal variability in drug exposure and subsequent high variability
in efficacy is observed after topical administration of anthelmintic compounds.
As it has been extensively demonstrated under experimental and field conditions,
understanding pharmacokinetic behaviour and identification of different factors
affecting drug activity is important for achieving optimal parasite control and
avoiding selection for drug resistance. The search for novel alternatives to
deliver enhanced drug concentrations within target helminth parasites may
contribute to avoiding misuse, and prolong the lifespan of existing and novel
anthelmintic compounds in the veterinary pharmaceutical market.
PMID- 28415923
TI - Hand grip strength determination for healthy males in Saudi Arabia: A study of
the relationship with age, body mass index, hand length and forearm circumference
using a hand-held dynamometer.
AB - Objectives To determine whether age, body mass index (BMI), hand length and
forearm circumference were predictive of hand grip strength in healthy Saudi
Arabian adult males. Methods This cross-sectional descriptive study recruited
healthy adult male volunteers. Their anthropometric characteristics including
age, BMI, hand length and forearm circumference were measured using routine
techniques. Hand grip strength was assessed using a Jamar(r) Hydraulic Hand
Dynamometer. The data were analysed using Pearson correlation coefficient ( r) as
well as by a stepwise multiple linear regression analysis. Results The study
included 116 healthy males who satisfied the inclusion criteria. A Pearson
correlation coefficient matrix demonstrated that all the four measures, age, BMI,
hand length and forearm circumference, were significantly correlated with hand
grip strength. Age had an inverse correlation with hand grip strength. The
anthropometric measures of hand length, age and forearm circumference accounted
for 44.2% (R2 0.442) of the variation of the hand grip strength. Conclusion Hand
length, age and forearm circumference significantly impacted on hand grip
strength in Saudi Arabian healthy adult males.
PMID- 28415924
TI - An assessment of the current treatment landscape for rheumatology patients in
Qatar: Recognising unmet needs and moving towards solutions.
AB - Objective This study assessed the mode of application (oral, intravenous or
subcutaneous (SC)) currently employed in the treatment of rheumatoid arthritis
(RA) in patients from Qatar in comparison with patients' individual preferences
for the mode of application of their treatment. Methods This study included 294
RA patients visiting three clinics at the main referral hospital in Qatar who
were interviewed using a standard questionnaire to determine their preference of
mode of application for their disease-modifying antirheumatic drug (DMARD)
treatment in relation to their currently employed mode of application. Results
The majority of patients were female (76%), and 93% of male patients and 61% of
female patients in the study clinics were of a nationality other than Qatari. The
highest patient preference recorded was for an oral therapy (69%), compared with
injection (23%) and intravenous (8%) therapy. In total, 85% of patients expressed
a preference to remain on oral therapy compared with 63% and 58% of intravenous
and SC injection patients indicating a preference to remain on their current
method of administration. Conclusions This high preference for oral therapies
highlights the considerable need for incorporation of new oral targeted synthetic
DMARD therapies into clinical practice within the region.
PMID- 28415926
TI - Urban and rural stroke mortality rates in China between 1988 and 2013: An age
period-cohort analysis.
AB - Objective To evaluate effects attributable to age, time period and birth cohort,
on stroke mortality data from urban and rural regions in China between 1988 and
2013. Methods Mortality data were obtained from the Chinese Health Statistics
Annual Report (1987-2001) and Chinese Health Statistics Yearbooks (2003-2014).
Population data were obtained from population censuses (i.e. 1982, 1990, 2000 and
2010). Data were analysed using an age-period-cohort (APC) model and intrinsic
estimation (IE) method. Results The age effect suggested that all older residents
had higher stroke mortality risk than younger residents. Period effect showed
that compared with figures for 1988, stroke mortality in 2013 was 1.8 times
higher for urban regions and 2.4 times higher for rural regions. After
controlling for age and period effects, cohorts born before the Chinese economic
reform had a steady decline in stroke mortality. However, mortality rates
increased and fluctuated in post-reform cohorts. Conclusions This APC-IE analysis
identified a modest period effect with large age and cohort contributions to both
the overall mortality and the disparity between urban and rural stroke mortality.
Identifying early life and cumulative risk factors for stroke, improving equality
in stroke prevention and care are needed to reduce the stroke mortality in China.
PMID- 28415927
TI - Transarterial embolization for renal angiomyolipomas: A single centre experience
in 79 patients.
AB - Objective To evaluate the long-term efficacy and safety of selective arterial
embolization (SAE) in the treatment of renal angiomyolipomas (AMLs). Methods This
was a retrospective review of medical records and imaging findings from patients
with renal AMLs who attended our clinic and received SAE between January 2007 and
January 2014. Only patents with complete medical records, preoperative computed
tomography scans using typical imaging and follow-up data were included. Results
A total of 79 patients were enrolled in the study. Technical and clinical success
rates were 100% and 91% ( n = 72), respectively. Only two patients experienced
major complications. Post-embolization syndrome (i.e. fever, abdominal pain,
nausea or vomiting) was reported in 68 (86%) patients, but all symptoms were mild
and resolved with conservative measures. Mean radiological and clinical follow-up
periods were 16.8 and 35.9 months, respectively. In 75 (95%) patients, tumours
decreased in size; mean +/- SD tumour size significantly decreased from 8.4 +/-
3.5 cm pre-embolization to 6.7 +/- 3.0 cm post-embolization . Conclusions This
study provides long-term evidence that SAE is a safe and effective method in the
treatment of patients with renal AMLs.
PMID- 28415928
TI - Incidence and risk factors for rectal pain after laparoscopic rectal cancer
surgery.
AB - Objective This study was performed to investigate the incidence of and potential
risk factors for rectal pain after laparoscopic rectal cancer surgery. Methods We
retrospectively analyzed data from 300 patients who underwent laparoscopic rectal
cancer surgery. We assessed the presence of rectal pain and categorized patients
into Group N (no rectal pain) or Group P (rectal pain). Results In total, 288
patients were included. Of these patients, 39 (13.5%) reported rectal pain and 14
(4.9%) had rectal pain that persisted for >3 months. Univariate analysis revealed
that patients in Group P had more preoperative chemoradiotherapy, more
ileostomies, longer operation times, more anastomotic margins of <2 cm from the
anal verge, more anastomotic leakage, and longer hospital stays. Multivariate
analysis identified an anastomotic margin of <2 cm from the anal verge and a long
operation time as risk factors. The presence of diabetes mellitus was a negative
predictor of rectal pain. Conclusions In this study, the incidence of rectal pain
after laparoscopic rectal cancer surgery was 13.5%. An anastomotic margin of <2
cm from the anal verge and a long operation time were risk factors for rectal
pain. The presence of diabetes mellitus was a negative predictor of rectal pain.
Thus, the possibility of postoperative rectal pain should be discussed
preoperatively with patients with these risk factors.
PMID- 28415929
TI - Retrospective analysis of a surgical innovation using the IDEAL framework:
radical cystectomy with epidural anaesthesia.
AB - Objectives To retrospectively analyse experience of radical cystectomy using
spinal/epidural anaesthesia and to classify this method using the IDEAL criteria.
Methods Data from patients who had undergone radical cystectomy using
spinal/epidural anaesthesia were evaluated retrospectively, focusing on clinical
data, intraoperative and perioperative parameters and postoperative
complications. Current literature reporting on this technique was reviewed and,
together with the present study, evaluated according to the IDEAL
recommendations. Results Three male patients aged 66-79 years who had undergone
radical cystectomy with epidural anaesthesia were identified. The operating time
ranged from 159-261 min and only minor complications occurred. Between 2013 and
2015, three published studies reported experiences with radical cystectomy with
epidural/spinal anaesthesia; one was prospective and two were retrospective in
nature and they included a total of 55 patients. According to the IDEAL
classification, the present study corresponds to stage 1 (idea) and overall the
surgical technique can be ranked as stage 2a (development). Conclusions Radical
cystectomy with epidural anaesthesia is feasible and applicable for those who are
not fit for general anaesthesia. The present study confirmed the functional
results of this technique, which can be classified as IDEAL stage 2a on the basis
of published studies.
PMID- 28415925
TI - The role of oxidative stress, inflammation and acetaminophen exposure from birth
to early childhood in the induction of autism.
AB - The wide range of factors associated with the induction of autism is invariably
linked with either inflammation or oxidative stress, and sometimes both. The use
of acetaminophen in babies and young children may be much more strongly
associated with autism than its use during pregnancy, perhaps because of well
known deficiencies in the metabolic breakdown of pharmaceuticals during early
development. Thus, one explanation for the increased prevalence of autism is that
increased exposure to acetaminophen, exacerbated by inflammation and oxidative
stress, is neurotoxic in babies and small children. This view mandates extreme
urgency in probing the long-term effects of acetaminophen use in babies and the
possibility that many cases of infantile autism may actually be induced by
acetaminophen exposure shortly after birth.
PMID- 28415931
TI - Comparison of dexmedetomidine and propofol for conscious sedation in inguinal
hernia repair: A prospective, randomized, controlled trial.
AB - Objective The ideal agents for conscious sedation during ambulatory inguinal
hernia repair are still unclear. We aimed to compare the analgesic, sedative,
haemodynamic, and side effects of dexmedetomidine with those of propofol in
combination with fentanyl for conscious sedation in patients undergoing inguinal
hernia repair. Methods Eighty patients undergoing unilateral inguinal hernia
repair were prospectively randomized to receive either dexmedetomidine (n = 40)
or propofol (n = 40). Dexmedetomidine and propofol dosages were adjusted to
maintain the targeted level of sedation. Results After administration of sedative
drugs, patients who received dexmedetomidine had a significantly lower heart
rate. The intraoperative requirement of fentanyl was significantly lower in
patients who received dexmedetomidine compared with patients who received
propofol. Administration of dexmedetomidine was associated with a reduced
postoperative pain score, longer time for onset of sedation, and a slightly
longer recovery time. No serious adverse events occurred in either group. The
patients' overall satisfaction score was comparable between the two groups.
Conclusion Dexmedetomidine is an effective adjuvant when co-administered with
fentanyl for conscious sedation in patients who undergo inguinal hernia repair.
Administration of dexmedetomidine decreases the requirement of fentanyl and the
pain score, but slightly prolongs the time to sedation and recovery.
PMID- 28415930
TI - Computed tomography-guided transthoracic biopsy: Factors influencing diagnostic
and complication rates.
AB - Objective This study was performed to assess the complication and diagnostic
rates of computed tomography (CT)-guided transthoracic needle biopsy of pulmonary
parenchymal and mediastinal lesions. Methods Patients who were suspected to have
a malignancy based on chest imaging and CT and could not be otherwise diagnosed
were evaluated. Results Sixty-five patients were included; 48 (73.8%) were male
and 17 (26.2%) were female. Their average age was 58 years. The lesion size
ranged from 11 to 105 mm. The most common specific histologic subtype was
adenocarcinoma, and the least common was lymphoma. The diagnostic rate was 90.8%.
The mean complication rate was 15.4%. Statistically significant associations were
found between the complication rate and needle size and between the needle path
length and lesion size. Conclusion CT-guided needle biopsy is an effective
diagnostic method for patients with mediastinal and parenchymal lesions before
thoracotomy. This method can also reliably differentiate benign and malignant
tumors.
PMID- 28415932
TI - The effects of corrective surgery on endothelial biomarkers and anthropometric
data in children with congenital heart disease.
AB - Objective To investigate the influence of surgical correction on biomarkers of
endothelial dysfunction in children with congenital heart disease and to evaluate
anthropometric data. Methods Children with pulmonary hypertension (PH) or
Tetralogy of Fallot (TOF) who were scheduled for corrective surgery were enrolled
in this prospective study. Age-matched healthy children were included as
controls. Demographic, haemodynamic and cardiac ultrasonography data were
collected. Blood samples were taken pre-surgery, 24-48 hours post-surgery and
again 3-6 months later. Several biomarkers (protein C, soluble platelet selectin
[CD62P], soluble endothelium selectin [CD62E], soluble leukocyte selectin
[CD62L], plasma von Willebrand Factor [vWF] atrial natriuretic peptide [ANP],
brain natriuretic peptide[(BNP] and insulin-like growth factor-1 [IGF-1]) were
measured. Results Sixty-three children (32 with PH, 15 with TOF, and 16 controls)
were enrolled. No significant differences between the PH and TOF groups were
observed in the expression of biomarkers pre- and post-surgery. IGF-1 levels were
closely related to anthropometric data, particularly those children with PH.
Expression of IGF-1 and weight/height normalized after corrective surgery.
Conclusions No significant endothelial dysfunction was observed in children with
PH or TOF before or after corrective surgery. Significant retardation of growth,
particularly weight, was found before surgery and may be related to IGF-1
suppression.
PMID- 28415933
TI - Incidence, risk factors and the effect of polyomavirus infection in hematopoietic
stem cell transplant recipients.
AB - Objective The effect of polyomavirus infection in HSCT recipients is poorly
understood. Methods We evaluated 38 HSCT recipients. Polyomavirus was detected by
nested qualitative polymerase chain reaction (PCR) assays of urine. The risk
factors for BK virus and JC virus were analysed. The kidney and liver functions
of infected and uninfected patients were compared. Results BK virus, JC virus,
and simian virus 40 were detected in 21%, 42%, and 0% of HSCT recipients
respectively. HCMV infection was found to be an independent risk factor for JC
virus infection (odds ratio (OR): 8.528), while transplants with mismatched HLA
are more susceptible to BK virus infection (OR: 12.000). Liver function of JC
virus-infected subjects was worse than that of uninfected subjects. Conclusion We
must be vigilant for opportunistic polyomavirus infections in HSCT recipients,
especially those with HCMV co-infection or a mismatched HLA transplant. When
unexplained liver function deterioration is observed, JC virus infection should
be considered.
PMID- 28415934
TI - Early abnormal liver enzyme levels may increase the prevalence of human
cytomegalovirus antigenaemia after hematopoietic stem cell transplantation.
AB - Objective Human cytomegalovirus (HCMV) infection is common after bone marrow
transplantation (BMT), and it increases morbidity and mortality for transplant
recipients. HCMV infection may cause hepatitis and elevate the liver enzymes
aspartate transferase (AST) and alanine transferase (ALT). This study aimed to
analyse the associations between liver enzyme levels and infection with HCMV
antigenaemia after BMT. Methods Data from 30 patients after BMT were collected at
different time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 months
post-transplantation). The patients were divided into the HCMV antigenaemia
positive and HCMV antigenaemia-negative groups according to a peripheral blood
pp65 antigen assay. Immunohistochemistry was used to identify HCMV pp65 antigen
and conventional methods were used to detect liver enzyme levels. Results Twelve
patients were pp65 antigenaemia-positive and 10 patients were positive in the
first 3 months post-transplant. Liver enzyme levels were increased after
positivity for HCMV antigenaemia (p = 0.034 and p = 0.018 for ALT and AST,
respectively). One month before antigenaemia, AST levels were higher in the HCMV
antigenaemia-positive group compared with the negative group (p = 0.006).
Conclusion HCMV antigenaemia mostly occurs in the early stage of post-BMT and
early abnormal liver enzyme levels may increase the chance of HCMV antigenaemia
after BMT.
PMID- 28415935
TI - Naringenin improves the healing process of thermally-induced skin damage in rats.
AB - Objective To evaluate the effect of the phenolic compound naringenin on thermal
burn-induced inflammatory responses and oxidative stress in rats. Methods First
degree thermal burn injuries were induced in shaved rats by 10 s immersion of the
back surface in water at 90C. Naringenin treatment (25, 50 and 100 mg/kg/day) was
initiated 24 h following burn injury, and continued for 7 days. On treatment day
7, serum tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, nitric
oxide (NO), prostaglandin (PG)E2, caspase-3, leukotriene (LT)-B4 and nuclear
factor (NF)-kappaB levels were quantified. Skin sample glutathione (GSH) and
thiobarbituric acid reactive substances (TBARS) levels, and catalase, superoxide
dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx)
activities, were also measured. Results Serum inflammatory biomarkers were
significantly increased in thermal-burn injured rats versus uninjured controls.
Naringenin significantly inhibited the increased proinflammatory markers at day 7
of treatment. Increased TBARS levels and decreased GSH levels in wounded skin
were significantly restored by naringenin treatment at day 7. SOD, catalase, GPx
and GST activities were markedly inhibited in wounded skin tissues, and were
significantly increased in naringenin-treated rats. Conclusion Naringenin
treatment showed anti-inflammatory and antioxidant effects in rats with thermal
burn-induced injury.
PMID- 28415936
TI - Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors:
National Health and Nutrition Examination Survey (NHANES) 1999-2010.
AB - Objectives To determine whether the associations with key risk factors in
patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are
different using data from the National Health and Nutrition Examination Survey
(NHANES) from 1999 to 2010. Methods The study analysed the prevalence and
association with risk factors of undiagnosed and diagnosed T2DM using a
regression model and a multinomial logistic regression model. Data from the
NHANES 1999-2010 were used for the analyses. Results The study analysed data from
10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM
increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was
significantly higher in non-Hispanic whites, in individuals <30 years old and in
those with near optimal (130-159 mg/dl) or very high (>=220 mg/dl) non-high
density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass
index, low economic status or low educational level had no effect on T2DM
diagnosis rates. Though diagnosed T2DM was associated with favourable
diet/carbohydrate intake behavioural changes, it had no effect on physical
activity levels. Conclusion The overall T2DM prevalence increased between 1999
and 2010, particularly for undiagnosed T2DM in patients that were formerly
classified as low risk.
PMID- 28415937
TI - Heparinized saline versus normal saline for maintaining peripheral venous
catheter patency in China: An open-label, randomized controlled study.
AB - Objective To evaluate the effects of heparin saline versus normal saline as
locking solution for maintaining patency in peripheral venous catheters in
Chinese patients. Methods This open-label, randomized controlled study was
conducted in two hepatobiliary surgery wards, where patients received identical
treatments, at a tertiary referral hospital. Patients were randomly divided into
a normal saline group (NS, 3 ml) or a heparin saline group (HS, 50 IU/ml, 3 ml)
for catheter sealing. Results The study enrolled 286 patients and 609 peripheral
venous catheters were included in the analysis. The patients in the two groups
had no local infections or catheter-related bloodstream infections. There were no
significant differences between the two groups in terms of the rate of catheter
obstruction, duration time, or the rates of phlebitis, infiltration, and
accidental catheter removal. Conclusions No significant differences in the
peripheral venous catheter sealing effects were observed between normal saline
and heparin saline usage in Chinese patients.
PMID- 28415938
TI - Indocyanine green detects sentinel lymph nodes in early breast cancer.
AB - Objective To explore the clinical value of indocyanine green (ICG) for the
fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel
lymph node biopsy (SLNB) in patients with early breast cancer. Methods This
retrospective study included female patients with breast cancer. Patients were
administered methylene blue and ICG using standard techniques. All SLNs that were
collected during surgery were submitted for pathological examination. SLNs were
defined as those that were either fluorescent, blue, fluorescent and blue or
palpably suspicious. Surgical complications, axillary recurrence, distant
metastasis and overall survival rates were observed postoperatively. Results A
total of 60 patients were enrolled in the study. The fluorescence detection rate
of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene
blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient.
Pathological assessment of intraoperative frozen specimens revealed SLN
metastases in 10 patients, who immediately underwent axillary lymph node
dissection. No patient had axillary recurrence or distant metastases, with a
survival rate of 100%. Patients who underwent SLNB showed good appearance in the
axillary wound, with no limited shoulder joint abduction and upper limb oedema.
Conclusion Fluorescence-guided SLNB has several advantages and is suitable for
clinical application.
PMID- 28415939
TI - Molecular diagnosis of Chinese patients with 21-hydroxylase deficiency and
analysis of genotype-phenotype correlations.
AB - Objective The spectrum of molecular defects in Chinese patients with 21
hydroxylase deficiency (21-OHD), and genotype-phenotype relationships are
unknown. Methods We screened eight patients with non-classical (NC) 21-OHD and 35
with classical 21-OHD, and detected nine known mutations. Results The most
frequent mutation among the 43 21-OHD cases was p.Ile172Asn (allele frequency,
36.0%), followed by c.290-13A/C > G (20.9%), Del (8.6%), p.Pro30Leu (7.0%),
p.Gln318Ter (7.0%), p.Val281Leu (4.7%), p.Arg356Trp (2.3%), p.[Ile236Asn;
Val237Glu; Met239Lys] (2.3%), and E3Delta8 bp (1.2%). The frequency spectrum of
CYP21A2 mutations in the Chinese population was similar to that in the Japanese
population, except that p.Val281Leu was identified in Chinese NC21-OHD patients
at a frequency of 25.0%, whereas it was absent in Japanese patients. We found
that genotype could predict phenotype in 88.3% of patients. Conclusion Some
characteristics appear to be unique to the Chinese population, but genotype was
strongly predictive of phenotype.
PMID- 28415940
TI - Thymoma metastatic to liver and pancreas: case report and review of the
literature.
AB - A 71-year-old man presented with a thymic mass involving the superior vena cava.
A mediastinoscopical biopsy initially suggested a diagnosis of type A thymoma.
After neoadjuvant chemotherapy, the patient underwent en-bloc thymectomy and
vascular resection for a pathology-confirmed type B3 thymoma involving the
superior vena cava, the left brachiocephalic vein and the distal part of the
right brachiocephalic vein. Adjuvant radiotherapy was administered. Two years
after the primary surgery, abdominal computed tomography (CT) and whole body
fluorodeoxyglucose (18-FDG) positron emission tomography (PET) scans showed a
single hepatic lesion that was treated with wedge liver resection. Pathological
examination confirmed metastatic type B3 thymoma. Almost 4 years later, abdominal
CT and 18-FDG PET revealed a 2.9-cm solid mass involving the body of the
pancreas. Distal pancreatectomy with lymph node dissection was performed.
Pathological examination showed a pancreatic metastasis from a type B3 thymoma,
without lymph node involvement. The patient is alive and free of disease 6 months
after the pancreatectomy (68 months after the initial thymectomy surgery). Intra
abdominal recurrence and pancreatic metastases are very uncommon manifestations
of thymoma, but this event should be kept in mind when an abdominal mass is seen
during follow-up.
PMID- 28415942
TI - Evaluation of health-related quality of life in patients with tuberculosis who
completed treatment in Kiribati.
AB - Objective To examine the health-related quality of life (HRQoL) and related
factors among patients with smear-positive and smear-negative pulmonary
tuberculosis (TB) within 2 years after completion of directly observed treatment,
short course (DOTS), and to compare their HRQoL with a comparison group of
community-dwelling individuals without TB in South Tarawa, Kiribati. Methods A
cross-sectional questionnaire survey was conducted among 206 pulmonary TB
patients who had completed DOTS and 214 individuals without TB, from July to
September 2012. HRQoL was measured using the Short Form (36) Health Survey (SF
36). Results The patients with TB had a statistically significantly higher
physical component summary (PCS) score and mental component summary (MCS) score
on the SF-36 than the comparison group after adjustment for background
characteristics. However, the differences did not exceed the 3-point threshold
for clinically significant differences. Multiple liner regression showed that
older age and presence of persistent symptoms after completion of DOTS were
related to a lower PCS score in TB patients. Patients who were smear-positive
before DOTS treatment had higher MCS scores than those who were smear-negative.
Conclusions Our results suggest the effectiveness of DOTS treatment. Health
professionals can enhance HRQoL among posttreatment TB patients by managing their
symptoms.
PMID- 28415941
TI - Endothelial protein C receptor polymorphisms and risk of sepsis in a Chinese
population.
AB - Objective To examine the potential relationship of EPCR polymorphisms and the
risk of sepsis in a Chinese population. Methods Snapshot SNP genotyping assays
and DNA sequencing methods were used to detect polymorphisms of the EPCR gene,
rs2069948C/T (2532C/T) and rs867186A/G (6936A/G), in 64 patients with sepsis and
in 113 controls. Soluble EPCR (sEPCR) was measured by ELISA. Results There were
significant differences in the allele and genotype frequencies of EPCR gene
rs2069948C/T and allele frequencies of rs867186A/G between male and female
patients and controls. Females carrying rs2069948 C/T genotype or T allele and
males carrying rs867186 A allele were associated with a significantly increased
risk of sepsis. Plasma sEPCR levels of sepsis patients were higher than controls
and showed no correlation with EPCR gene polymorphisms. Conclusions EPCR
polymorphisms may be associated with increased risk of sepsis, but this has no
effect on the release of sEPCR in patients with sepsis.
PMID- 28415943
TI - Effects of scalp block with bupivacaine versus levobupivacaine on haemodynamic
response to head pinning and comparative efficacies in postoperative analgesia: A
randomized controlled trial.
AB - Objective This study was performed to determine the effects of scalp blocks with
bupivacaine versus levobupivacaine on the haemodynamic response during craniotomy
and the efficacies and analgesic requirements of these drugs postoperatively.
Methods This randomized, prospective, placebo-controlled, double-blind study
included 90 patients (age, 18-85 years; American Society of Anesthesiologists
physical status, I or II). The patients were randomly divided into three groups:
those who received 20 mL of 0.5% bupivacaine (Group B, n = 30), 20 mL of 0.5%
levobupivacaine (Group L, n = 30), or saline as a placebo (Group C, n = 30).
Scalp blocks were performed 5 min before head pinning. The primary outcome was
the mean arterial pressure (MAP), and the secondary outcomes were the heart rate
(HR), visual analogue scale (VAS) scores, and additional intraoperative and
postoperative drug use. Postoperative pain was evaluated using a 10-cm VAS.
Results During head pinning and incision, the MAP and HR were significantly
higher in Group C. The additional drug requirement for intraoperative
hypertension and tachycardia was significantly higher in Group C. There were no
significant differences in MAP, HR, or VAS scores between Groups B and L.
Conclusion Both bupivacaine and levobupivacaine can be effectively and safely
used for scalp blocks to control haemodynamic responses and postoperative pain.
PMID- 28415945
TI - Pseudomonas aeruginosa endophthalmitis caused by accidental iatrogenic ocular
injury with a hypodermic needle.
AB - Iatrogenic traumatic endophthalmitis is a rare but serious ocular infection that
can lead to severe vision loss. A 44-year-old man presented with pain and
decreased vision in the right eye 4 hours after injury with a hypodermic needle
during irrigation of his eye. Slit-lamp examination revealed a penetrating
corneal puncture and iris hole in the right eye. Twenty hours later, his visual
acuity had decreased to hand motion, and severe fibrinoid uveitis was noted. He
immediately underwent irrigation of the anterior chamber and intravitreal
antibiotic injection. The right eye became painful again, and emergent vitrectomy
combined with lensectomy was performed along with intravitreal antibiotic
administration. The patient remained stable during the 2-month follow-up.
Standard practice should be adopted when irrigating the eye to prevent this type
of injury, and emergent surgical intervention is very important to preserve
visual function.
PMID- 28415944
TI - Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic
kidney disease: a meta-analysis.
AB - Objective This meta-analysis aimed to investigate the efficacy and safety of
pentoxifylline (PTF) plus angiotensin-converting enzyme inhibitors
(ACEIs)/angiotensin receptor blockers (ARBs) for proteinuria and kidney function
in chronic kidney disease (CKD). Methods CENTRAL, EMBASE, Ovid-MEDLINE, PubMed,
and CNKI were searched for relevant, randomized, controlled trials (RCTs). A meta
analysis was performed to review the effect of PTF plus ACEIs/ARBs vs. ACEIs/ARBs
alone on proteinuria and kidney function in CKD. Results Eleven RCTs including
705 patients were retrieved. PTF plus ACEI/ARB treatment significantly decreased
proteinuria in patients with CKD within 6 months (standard mean difference [SMD]
0.52; 95% CI -0.90 to 0.15; I2 = 68%) and significantly attenuated a decrease in
estimated glomerular filtration rate (eGFR) in patients with stages 3-5 CKD after
6 months of treatment (standard mean difference [SMD] 0.30; confidence limit [Cl]
95% CI 0.06 to 0.54; I2 = 0%). PTF plus ACEIs/ARBs for 9 to 12 months
significantly reduced albuminuria in patients with CKD (SMD-0.30, 95% CI -0.57 to
0.03; I2 = 0%) and alleviated the decline in eGFR in patients with stages 3-5 CKD
(SMD 0.51; 95% CI 0.06 to 0.96; I2 = 61%). Conclusion The combination of an ACEI
or ARB and PTF has a protective effect in reducing proteinuria by ameliorating
the decline in eGFR in patients with stages 3-5 CKD.
PMID- 28415946
TI - Azacitidine-induced acute lung injury in a patient with therapy-related
myelodysplastic syndrome.
AB - Azacitidine is a first-in-class demethylating agent, and it is widely used
globally as a first-line treatment for higher-risk myelodysplastic syndrome
(MDS). Here, we report the case of a patient with MDS who suffered from a rare
adverse event, an acute lung injury (ALI), which was suspected to have been
caused by azacitidine and was successfully treated with corticosteroids. As it is
a rare, but critical, adverse event, clinicians should consider ALI as one of the
differential diagnoses in cases where 1) pneumonia and fever of unknown etiology
arise in MDS patients treated with azacitidine, 2) antimicrobial agents are not
effective, and 3) microbiological tests produce negative results.
PMID- 28415947
TI - Effect of pretreatment with midazolam on etomidate-induced myoclonus: A meta
analysis.
AB - Objective To investigate the effect of pretreatment with midazolam on myoclonus
induced by etomidate injection. Methods A meta-analysis was performed using
Review Manager software, version 5.2. Two researchers independently searched
PubMed, Cochrane Library, and Embase(r) databases for randomized controlled
trials involving patients who underwent etomidate induced general anaesthesia
with or without midazolam pretreatment, published between 1990 and 2016. Outcome
measures comprised overall myoclonus incidence rate and incidence rate classified
by degree of myoclonus following etomidate injection. Data were assessed using a
fixed effects model. Results Five studies, comprising 302 patients, were included
for analysis. Overall incidence rate of etomidate injection-induced myoclonus was
significantly lower in the pooled midazolam group versus controls (relative risk
[RR] 0.34, 95% confidence interval [CI] 0.26, 0.44); Results subgrouped by degree
of myoclonus showed significantly lower incidence in midazolam groups versus
control groups for mild myoclonus (RR 0.56, 95% CI 0.39, 0.80); moderate
myoclonus (RR 0.20, 95% CI 0.10, 0.41); and severe myoclonus (RR 0.12, 95% CI
0.04, 0.39). Conclusion Midazolam can effectively prevent etomidate-induced
myoclonus, and alleviate the degree of etomidate-induced myoclonus.
PMID- 28415948
TI - Use of platelet-rich plasma for regeneration in non-vital immature permanent
teeth: Clinical and cone-beam computed tomography evaluation.
AB - Objective This study was performed to assess the clinical and radiological
outcomes of a revascularization procedure in immature teeth with apical
periodontitis using platelet-rich plasma (PRP). The PRP protocol and conventional
revascularization protocol, which used a blood clot as the scaffold, were
compared. Methods Thirty non-vital immature permanent teeth were randomly
categorized into two groups. After disinfecting the root canal space with triple
antibiotic paste (1:1:1 ciprofloxacin, metronidazole, and cefaclor), a tissue
scaffold was created using either PRP or a blood clot (control) and covered with
white mineral trioxide aggregate. All cases were followed up clinically and
radiographically for 12 months. Differences in bone density, root length, and
lesion size were calculated using preoperative and postoperative computed
tomography images. The means of the differences in individual parameters in the
blood clot and PRP groups were compared using the Mann-Whitney U test. Results
After 5 months, sensitivity tests (cold and electric pulp tests) elicited a
delayed positive response in 23 sites. At 12 months, cone-beam computed
tomography revealed resolution or a decrease in lesion size and an increase in
bone density in all 30 (100%) teeth. Additionally, continued root development was
observed in 22 (73%) teeth and early root growth was observed in the test group
(mineral trioxide aggregate with PRP). Conclusions The results of this study
suggest that PRP can serve as a successful scaffold for regenerative endodontic
treatment. With the exception of a significant increase in root length, the
results of treatment with PRP were not significantly different from those of the
conventional protocol using a blood clot as the scaffold.
PMID- 28415949
TI - beta-catenin promotes intracellular bacterial killing via suppression of
Pseudomonas aeruginosa-triggered macrophage autophagy.
AB - Objective To investigate beta-catenin-mediated bacterial elimination during
Pseudomonas aeruginosa infection of macrophage-like RAW264.7 cells. Methods Cell
viability and catenin beta 1 ( CTNNB1) expression in RAW264.7 cells following P.
aeruginosa infection versus uninfected cells, were detected by cell counting kit
8 assay and beta-catenin Western blots. RAW264.7 cells with CTNNB1 overexpression
were established with beta-catenin lentivirus using flow cytometry and clonogenic
limiting dilution assays. Bacterial killing was measured by plate counts;
phagocytosis and nitric oxide (NO) were measured by flow cytometry; and reactive
oxygen species (ROS) were measured using Griess reaction. Autophagy was
determined by microtubule-associated protein 1 light chain 3 alpha
phosphatidylethanolamine conjugate (LC3-II) protein levels and formation of LC3
puncta, using Western blot and immunofluorescence staining. Results Following P.
aeruginosa infection, RAW264.7 cell beta-catenin levels were reduced in a time-
and multiplicity of infection-dependent manner. CTNNB1 overexpression was
associated with increased P. aeruginosa elimination, but had no effect on
RAW264.7 cell phagocytosis, ROS and NO. CTNNB1 overexpression reduced LC3-II
levels and formation of LC3 puncta, suggesting autophagy inhibition.
Rapamycin/starvation-induced autophagy resulted in reduced bacterial killing
following P. aeruginosa infection. Conclusion beta-catenin may promote bacterial
killing via suppression of P. aeruginosa-induced macrophage autophagy.
PMID- 28415950
TI - Ovarian cystectomy in the treatment of apparent early-stage immature teratoma.
AB - Objective To investigate the role of ovarian cystectomy in patients with early
stage immature teratoma. Methods A retrospective review was undertaken on
patients diagnosed pathologically with immature teratoma and with malignant
lesions confined to the ovary. Patients were included if they had been treated
between January 1997 and December 2015 at the Obstetrics and Gynaecology Hospital
of Fudan University, Shanghai, China. Relevant demographic and clinical data were
retrieved from the medical records. Results Forty-three patients were included in
the study; 14 underwent ovarian cystectomy (group 1) and 29 underwent unilateral
salpingo-oophorectomy (USO; group 2). Three of the patients who underwent USO
relapsed and required a second surgical intervention. The 5-year disease-free
survival rates were 100% and 88%for groups 1 and 2, respectively. There were no
significant differences between the two groups in terms of survival or
postoperative fertility outcomes. Univariate and multivariate analysis further
revealed that ovarian cystectomy was not a poor prognostic indicator for disease
free survival. Conclusion These current data suggest that ovarian cystectomy can
be considered for patients with apparent early-stage immature teratoma as it
preserves fertility as much as possible without adversely impacting upon
survival.
PMID- 28415951
TI - Superior versus anteroinferior plating of displaced midshaft clavicular fracture
in patients older than 60 years.
AB - Objective To compare superior versus anteroinferior plating for displaced
midshaft clavicular fracture in elderly patients. Methods We retrospectively
compared the functional result, parameters, and perioperative course of displaced
midshaft clavicular fracture in 42 patients >60 years treated with a 3.5-mm
reconstruction plate placed superiorly versus anteroinferiorly. Results Groups
were similar with regard to age, sex, bone mineral density, cause of injury, and
fracture pattern. The superiorly-plated group had a significantly longer
operation time and greater blood loss, complications and implant prominence.
Constant scores were significantly higher for the anteroinferiorly-plated group
than the superiorly-plated group at 3 months postoperatively; however, there was
no difference between groups at final follow-up. Conclusion While both
anteroinferior and superior plate placement are safe and effective for displaced
midclavicular fractures in patients >60 years, the anteroinferior approach
involves less operation time, blood loss, complications and implant prominence,
and enables faster return to normal activities.
PMID- 28415952
TI - Effective treatment of ketamine-associated cystitis with botulinum toxin type a
injection combined with bladder hydrodistention.
AB - Objective Ketamine-associated cystitis (KAC) has been described in a few case
reports, but its treatment in a relatively large number of patients has not been
documented. This study aimed to describe our experience of treatment of 36
patients with KAC. Methods Thirty-six patients (30 males and 6 females, aged 19
38 years) with KAC, who had previously taken a muscarinic receptor blocker and/or
antibiotics, but without symptomatic relief, were treated with botulinum toxin A
injection combined with bladder hydrodistention. Urodynamic testing, and the
O'Leary-Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI)
were used to evaluate baseline values and improvement before and after the
treatment. Results One month post-treatment, all patients achieved marked relief
of symptoms. The nocturia time was markedly reduced, while bladder capacity, the
interval between micturition, the void volume, and the maximum flow rate were
remarkably increased at 1 month. Additionally, the ICSI and ICPI were
significantly improved. Conclusion Botulinum toxin A injection along with bladder
hydrodistention is effective for managing KAC.
PMID- 28415953
TI - Influence of etanercept on leptin and ghrelin secretion in children with juvenile
idiopathic arthritis.
AB - Objective To assess possible changes in leptin and ghrelin secretion due to
etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA
and 16 age-matched controls were enrolled into this prospective, cross-sectional
study. Serum leptin, total and acyl ghrelin were measured in addition to white
blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept
and 25 conventional therapies (including methotrexate) for JIA. There was no
difference between treatment and control groups in leptin or ghrelin levels and
no evidence of a relationship between leptin and ghrelin in patients with JIA. In
all children with JIA there was a correlation between leptin and body mass index
(BMI). However, compared with children in the conventional treatment group,
children in the etanercept group showed a positive correlation between total
ghrelin and BMI and those with a low BMI showed a negative correlation between
acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin
concentrations were found when patients with JIA and controls were compared or
when patients who received etanercept were compared with those who received
conventional treatment for JIA.
PMID- 28415954
TI - Healthcare budgets across continents: at crossroads - publish or perish.
PMID- 28415956
TI - The relationship between neutrophil-lymphocyte ratio and acute aortic dissection.
PMID- 28415957
TI - "So Happy I Could Shout!" and "So Happy I Could Cry!" Dimorphous expressions
represent and communicate motivational aspects of positive emotions.
AB - Happiness can be expressed through smiles. Happiness can also be expressed
through physical displays that without context, would appear to be sadness
(tears, downward turned mouths, and crumpled body postures) and anger (clenched
jaws, snarled lips, furrowed brows, and pumped fists). These seemingly
incongruent displays of happiness, termed dimorphous expressions, we propose,
represent and communicate expressers' motivational orientations. When
participants reported their own aggressive expressions in positive or negative
contexts, their expressions represented positive or negative emotional
experiences respectively, imbued with appetitive orientations (feelings of
wanting to go). In contrast, reported sad expressions, in positive or negative
contexts, represented positive and negative emotional experiences respectively,
imbued with consummatory orientations (feelings of wanting to pause). In six
additional experiments, participant observers interpreted that aggression
displayed in positive contexts signalled happy-appetitive states, and sadness
displayed in positive contexts signalled happy-consummatory states. Implications
for the production and interpretation of emotion expressions are discussed.
PMID- 28415958
TI - Glycyrrhizic acid exerts anti-inflammatory effect to improve cerebral vasospasm
secondary to subarachnoid hemorrhage in a rat model.
AB - This study aimed to investigate the therapeutic effect of glycyrrhizic acid (GA)
on the cerebral vasospasm (CVS) in a rat subarachnoid hemorrhage (SAH) model and
to explore the potential mechanism. A total of 44 healthy male rats were randomly
assigned into 3 groups: control group (n = 12), SAH group (n = 16) and GA group
(n = 16). No treatment was conducted in control group; in SAH group and GA group,
experimental CVS was induced using a double-hemorrhage model and then rats were
intraperitoneally injected with normal saline and GA at 10 mg/kg, respectively,
once daily. Three days later, neurological function was evaluated. Then, animals
were sacrificed, and the basilar artery was collected. The inner diameter and
vascular wall thickness were determined. Western blotting was employed to detect
high mobility group protein B1 (HMGB1) protein expression and RT-PCR to detect
the mRNA expression of IL-1beta, IL-6, TNF-alpha, and IL-10 in the basilar
artery. GA treatment significantly improved the neurological function following
SAH. In GA group, the basilar artery diameter increased markedly and vascular
wall thickness reduced significantly when compared with SAH group (p < 0.05).
HMGB1 protein expression and mRNA expression of IL-1beta, IL-6, TNF-alpha, and IL
10 in SAH group were significantly higher than in control group (p < 0.05).
However, GA dramatically reduced IL-1beta, IL-6, and TNF-alpha, and further
elevated IL-10 expression as compared to SAH group (p < 0.05). GA may inhibit
HMGB1 expression and subsequent production of inflammatory cytokines to prevent
CVS following SAH.
PMID- 28415959
TI - The Practices and Meanings of Care for Nurses Working on a Pediatric Bone Marrow
Transplant Unit.
AB - Bone marrow transplant (BMT) units are stressful work environments with high
staff burnout, anxiety, and turnover. A qualitative study was undertaken to
better understand care for nurses within the context of their clinical practice
on a pediatric BMT unit. Understanding care practices for BMT nurses will allow
us to design interventions and provide appropriate support for this subspecialty
of nurses. Focus groups were held with 24 nurses as key participants, and 2 focus
groups with general participants: unit management (N = 2) and caregivers of
inpatients (N = 7). Data were analyzed using a thematic analysis. Data were
transcribed verbatim and coded to consensus by members of the research team. Five
themes emerged from the data: ( a) experiencing stressful situations that impede
care, ( b) growing and developing personally and professionally, ( c) providing
trustworthy and respectful care, ( d) acquiring meaningful coping skills, and (
e) sharing with others versus isolation. Stress management, professional
development, and interdisciplinary communication were areas that emerged for
potential intervention.
PMID- 28415960
TI - Chemotherapy Safety Standards: A Pediatric Perspective.
PMID- 28415961
TI - Changing practices and shifting meanings of female genital cutting among the
Maasai of Arusha and Manyara regions of Tanzania.
AB - Using mixed methods that combined participant observation and semi-structured in
depth interviews, this study looked at changing practices and shifting meanings
of female genital cutting among the Maasai people in Tanzania. The findings
suggest that an increasing social pressure to abandon female genital cutting has
inspired the hiding of the practice, causing the actual cutting to become
detached from its traditional ceremonial connotations. This detaching of cutting
from ceremony has created a shift in meanings: the ceremony still carries the
meaning of passage into adulthood, while the cutting seems to function as a way
of inscribing Maasai identity into the body. The detaching of genital cutting
from ceremony offers those willing to continue the practice the opportunity to do
so without being prosecuted, and those unwilling to undergo or perform the
practice the opportunity to evade it by faking the cutting without being socially
sanctioned for it. Findings also suggest changing attitudes towards the practice
among the younger generation as the result of education. Maasai culture and the
practice of female genital cutting are not static but actively challenged and
reinterpreted from within the community, with formally schooled and women taking
up leading roles in reshaping gender norms.
PMID- 28415962
TI - Guest Editorial: Introducing a new section.
PMID- 28415963
TI - Impact of the MDM2 splice-variants MDM2-A, MDM2-B and MDM2-C on cytotoxic stress
response in breast cancer cells.
AB - BACKGROUND: The murine double minute 2 (MDM2) is an oncogene and a negative
regulator of the tumor suppressor protein p53. MDM2 is known to be amplified in
numerous human cancers, and upregulation of MDM2 is considered to be an
alternative mechanism of p53 inactivation. The presence of many splice variants
of MDM2 has been observed in both normal tissues and malignant cells; however
their impact and functional properties in response to chemotherapy treatment are
not fully understood. Here, we investigate the biological effects of three widely
expressed alternatively spliced variants of MDM2; MDM2-A, MDM2-B and MDM2-C, both
in unstressed MCF-7 breast cancer cells and in cells subjected to chemotherapy.
We assessed protein stability, subcellular localization and induction of
downstream genes known to be regulated by the MDM2-network, as well as impact on
cellular endpoints, such as apoptosis, cell cycle arrest and senescence. RESULTS:
We found both the splice variants MDM2-B and -C, to have a much longer half-life
than MDM2 full-length (FL) protein after chemotherapy treatment indicating that,
under stressed conditions, the regulation of degradation of these two variants
differs from that of MDM2-FL. Interestingly, we observed all three splice
variants to deviate from MDM2-FL protein with respect to subcellular
distribution. Furthermore, while MDM2-A and -B induced the expression of the pro
apoptotic gene PUMA, this effect did not manifest in an increased level of
apoptosis. CONCLUSION: Although MDM2-B induced slight changes in the cell cycle
profile, overall, we found the impact of the three MDM2 splice variants on
potential cellular endpoints upon doxorubicin treatment to be limited.
PMID- 28415964
TI - Quantitative trait locus analysis of heterosis for plant height and ear height in
an elite maize hybrid zhengdan 958 by design III.
AB - BACKGROUND: Plant height (PH) and ear height (EH) are two important agronomic
traits in maize selection breeding. F1 hybrid exhibit significant heterosis for
PH and EH as compared to their parental inbred lines. To understand the genetic
basis of heterosis controlling PH and EH, we conducted quantitative trait locus
(QTL) analysis using a recombinant inbreed line (RIL) based design III population
derived from the elite maize hybrid Zhengdan 958 in five environments. RESULTS: A
total of 14 environmentally stable QTLs were identified, and the number of QTLs
for Z1 and Z2 populations was six and eight, respectively. Notably, all the eight
environmentally stable QTLs for Z2 were characterized by overdominance effect
(OD), suggesting that overdominant QTLs were the most important contributors to
heterosis for PH and EH. Furthermore, 14 environmentally stable QTLs were
anchored on six genomic regions, among which four are trait-specific QTLs,
suggesting that the genetic basis for PH and EH is partially different.
Additionally, qPH.A-1.3, modifying about 10 centimeters of PH, was further
validated in backcross populations. CONCLUSIONS: The genetic basis for PH and EH
is partially different, and overdominant QTLs are important factors for heterosis
of PH and EH. A major QTL qPH.A-1.3 may be a desired target for genetic
improvement of maize plant height.
PMID- 28415965
TI - The Pregnancy Environment and Lifestyle Study (PETALS): a population-based
longitudinal multi-racial birth cohort.
AB - BACKGROUND: Increasing recognition has been received regarding the proven and
suggested links between multi-level environmental exposures on a broad scale
(e.g., chemical, clinical, behavioral, physical and social) and health deficits
originated from the critical window of development. However, such prospective
human data are limited. In 2016, the National Institutes of Health funded 35
centers comprising 84 extant cohorts for the Environmental Influences on Child
Health Outcomes (ECHO) pediatric cohorts program. The Pregnancy Environment and
Lifestyle Study (PETALS) is one of the cohorts at the participating centers of
Kaiser Permanente Northern California (KPNC). METHODS: PETALS was originally
funded by the National Institute of Environmental Health Sciences to establish a
longitudinal birth cohort of 3,350 mother-infant pairs and conduct a nested case
control study of 300 women with gestational diabetes (GDM) and 600 matched
controls to investigate the associations between phenol exposures in first and
second trimesters and GDM risk and the related outcome of infant macrosomia. This
paper describes the prospective cohort design of PETALS, current research
activities, and cohort profile of enrolled women who delivered as of February
2016. Women are enrolled from the KPNC membership. Fasting blood draw, urine
collection, anthropometric measurements, and questionnaires on health history and
lifestyle are completed at baseline and follow-up clinic visits with targeted
windows of 10-13 and 16-19 weeks of gestation, respectively. Further, women's
clinical and health assessments before and after the index pregnancy in addition
to their children's birth outcomes and health information can be abstracted from
electronic health records, allowing future follow-up. Study data could also be
linked and extended to a myriad of additional observational data including
environmental and area-level databases and census data. DISCUSSION: In this
racially- and ethnically-diverse pregnancy cohort, the generated biospecimen and
data repository will establish a comprehensive framework which may provide unique
opportunities to address a multitude of research questions on the intrauterine
environment and adverse pregnancy and birth outcomes in a representative multi
racial/ethnic population with generalizable findings.
PMID- 28415966
TI - Birth by caesarean section and school performance in Swedish adolescents- a
population-based study.
AB - BACKGROUND: Our objective was to assess the impact of obstetric mode of delivery,
and in particular birth by Caesarean section (CS), on school performance in
adolescents using a large, population-based cohort. METHODS: We extracted data
from the Swedish Medical Birth Register and National School Register. We included
all live singleton births in Sweden from 1982-1995 (n = 1,489,925). School grades
were reported on a scale from 0 to 320, scores less than 160 (i.e. "pass") were
considered to be "poor school performance." Mode of delivery was categorised as:
unassisted vaginal delivery (VD), assisted VD, elective CS and emergency CS. We
measured the association between mode of delivery and "poor school performance"
using logistic regression. We then used quantile regression to assess the
association between mode of delivery and school performance across the
distribution of scores. We adjusted for maternal age, parity, small and large for
gestational age, gestational age, maternal country of birth, maternal depression,
non-affective disorder or bipolar disorder, parental income at time of birth, and
parental social welfare at time of birth. We also conducted sensitivity analyses
to investigate the association further. RESULTS: With logistic regression
analysis, the adjusted odds ratio (aOR) of assisted VD and poor school
performance, compared to unassisted VD, was 1.06 (95% CI: 1.03-1.08). For
elective CS it was 1.06 (95% CI:1.03-1.09) and for emergency CS it was 1.12 (95%
CI: 1.09-1.15). With quantile regression, assisted VD showed little difference in
scores, when compared to unassisted VD, at any point across the distribution.
Elective CS was associated with a 1-3 point decrease in scores, and emergency CS
was associated with a 2-5 point decrease in scores. CONCLUSION: A slight
association was found between birth by CS and school performance. However, the
effect was quite small and given the complex nature of the relationship, should
be interpreted with caution.
PMID- 28415967
TI - Chewing gum for intestinal function recovery after caesarean section: a
systematic review and meta-analysis.
AB - BACKGROUND: Gum chewing has been reported to enhance the intestinal function
recovery after caesarean section, current perspectives and practice guidelines
vary widely on the use of gum chewing, more studies on the role of gum chewing
after caesarean section are needed. METHODS: We performed a comprehensive,
systematic meta-analysis of randomized controlled trials (RCTs) on the efficacy
of gum chewing after caesarean section. Studies were identified by searching
EMBASE et al database (until June 30, 2016). Summary odd ratios or weighted mean
differences with 95% confidence intervals were calculated for each outcome with
fixed- or random-effects model. RESULTS: Ten RCTs with a total of 1659 women were
included in our meta-analysis. Gum chewing provided significant benefits in
reducing the time to first passage of flatus, first defecation, first bowel
sound, first bowel movement and the length of hospital stay, but not in the time
to first feeling of hunger. CONCLUSIONS: Gun chewing hastens the intestinal
function recovery after caesarean section and offers a safe and inexpensive
option. High-quality and larger-scale RCTs are still warranted to clarify the
role of gum chewing in intestinal function recovery after caesarean section.
PMID- 28415968
TI - How to explore the needs of informal caregivers of individuals with cognitive
impairment in Alzheimer's disease or related diseases? A systematic review of
quantitative and qualitative studies.
AB - BACKGROUND: This study aims to review the methodologies used to identify the
needs, the existing needs assessment instruments and the main topics of needs
explored among caregivers of patients with mild cognitive impairment to dementia.
METHODS: MEDLINE, PsycINFO, The Cochrane Library and Web of science were searched
from January 1980 to January 2017. Research studies in English or French were
eligible for inclusion if they fulfilled the following criteria: quantitative,
qualitative and mixed method studies that used instrument, focus group or semi
structured interviews to assess the informal caregiver's needs in terms of
information, coping skills, support and service. RESULTS: Seventy studies (n = 39
quantitative studies, n = 25 qualitative studies and n = 6 mixed method studies)
met the inclusion criteria and were included. Thirty-six quantitative instruments
were identified but only one has been validated for the needs assessment of
dementia caregivers: the Carer's Needs Assessment for Dementia (CNA-D). The main
areas of needs explored in these instruments were: information, psychosocial,
social, psychoeducational and other needs. CONCLUSIONS: No instrument has been
developed and validated to assess the needs of informal caregivers of patients
with cognitive impairment, whatever the stage and the etiology of the disease. As
the perceived needs of caregivers may evolve with the progression of the disease
and the dementia transition, their needs should be regularly assessed.
PMID- 28415969
TI - Carbapenem resistance, inappropriate empiric treatment and outcomes among
patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia
and sepsis.
AB - BACKGROUND: Drug resistance among gram-negative pathogens is a risk factor for
inappropriate empiric treatment (IET), which in turn increases the risk for
mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae
(CRE) on the risk of IET and of IET on outcomes in patients with
Enterobacteriaceae infections. METHODS: We conducted a retrospective cohort study
in Premier Perspective database (2009-2013) of 175 US hospitals. We included all
adult patients with community-onset culture-positive urinary tract infection
(UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis
in the setting of respiratory failure, treated with antibiotics within 2 days of
admission. We employed regression modeling to compute adjusted association of
presence of CRE with risk of receiving IET, and of IET on hospital mortality,
length of stay (LOS) and costs. RESULTS: Among 40,137 patients presenting to the
hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were
CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non
CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001),
and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those
with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009)
and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation
35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE
subjects, respectively. CRE patients were 3* more likely to receive IET than non
CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong
predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence
interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted
rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of
5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95%
confidence interval $9497, $11,126, p < 0.001) in costs. CONCLUSIONS: In this
large US database, the prevalence of CRE among patients with Enterobacteriaceae
UTI, pneumonia or sepsis was comparable to other national estimates. Infection
with CRE was associated with a four-fold increased risk of receiving IET, which
in turn increased mortality, LOS and costs.
PMID- 28415970
TI - Drosophila melanogaster retrotransposon and inverted repeat-derived endogenous
siRNAs are differentially processed in distinct cellular locations.
AB - BACKGROUND: Endogenous small interfering (esi)RNAs repress mRNA levels and
retrotransposon mobility in Drosophila somatic cells by poorly understood
mechanisms. 21 nucleotide esiRNAs are primarily generated from retrotransposons
and two inverted repeat (hairpin) loci in Drosophila culture cells in a Dicer2
dependent manner. Additionally, proteins involved in 3' end processing, such as
Symplekin, CPSF73 and CPSR100, have been recently implicated in the esiRNA
pathway. RESULTS: Here we present evidence of overlap between two essential RNA
metabolic pathways: esiRNA biogenesis and mRNA 3' end processing. We have
identified a nucleus-specific interaction between the essential esiRNA cleavage
enzyme Dicer2 (Dcr2) and Symplekin, a component of the core cleavage complex
(CCC) required for 3' end processing of all eukaryotic mRNAs. This interaction is
mediated by the N-terminal 271 amino acids of Symplekin; CCC factors CPSF73 and
CPSF100 do not contact Dcr2. While Dcr2 binds the CCC, Dcr2 knockdown does not
affect mRNA 3' end formation. RNAi-depletion of CCC components Symplekin and
CPSF73 causes perturbations in esiRNA abundance that correlate with fluctuations
in retrotransposon and hairpin esiRNA precursor levels. We also discovered that
esiRNAs generated from retrotransposons and hairpins have distinct physical
characteristics including a higher predominance of 22 nucleotide hairpin-derived
esiRNAs and differences in 3' and 5' base preference. Additionally,
retrotransposon precursors and derived esiRNAs are highly enriched in the nucleus
while hairpins and hairpin derived esiRNAs are predominantly cytoplasmic similar
to canonical mRNAs. RNAi-depletion of either CPSF73 or Symplekin results in
nuclear retention of both hairpin and retrotransposon precursors suggesting that
polyadenylation indirectly affects cellular localization of Dcr2 substrates.
CONCLUSIONS: Together, these observations support a novel mechanism in which
differences in localization of esiRNA precursors impacts esiRNA biogenesis.
Hairpin-derived esiRNAs are generated in the cytoplasm independent of Dcr2
Symplekin interactions, while retrotransposons are processed in the nucleus.
PMID- 28415971
TI - An evolutionarily conserved transcriptional response to viral infection in
Caenorhabditis nematodes.
AB - BACKGROUND: Caenorhabditis elegans is a powerful model organism for probing many
biological processes including host-pathogen interactions with bacteria and
fungi. The recent identification of nematode viruses that naturally infect C.
elegans and Caenorhabditis briggsae provides a unique opportunity to define host
virus interactions in these model hosts. RESULTS: We analyzed the transcriptional
response of pathogen infected C. elegans and C. briggsae by RNA-seq. We
identified a total of 320 differentially expressed genes (DEGs) in C. elegans
following Orsay virus infection. The DEGs of known function were enriched for
ubiquitin ligase related genes; however, the majority of the genes were of
unknown function. Interestingly, many DEGs that responded to Orsay virus
infection were similar to those induced by Nematocida parisii infection, which is
a natural microsporidia pathogen of C. elegans that like Orsay virus infects
intestinal cells. Furthermore, comparison of the Orsay virus DEGs in C. elegans
to Santeuil virus DEGs in C. briggsae identified 58 C. elegans genes whose
orthologs were likewise differentially expressed in C. briggsae, thereby defining
an evolutionarily conserved response to viral infection. CONCLUSIONS: The two
different species C. elegans and C. briggsae, which diverged ~18 million years
ago, share a common set of transcriptionally responsive genes to viral infection.
Furthermore, a subset of these genes were also differentially expressed following
infection by a eukaryotic pathogen, N. parisii, suggesting that these genes may
constitute a broader pan-microbial response to infection.
PMID- 28415972
TI - Community-based survey during rabies outbreaks in Rangjung town, Trashigang,
eastern Bhutan, 2016.
AB - BACKGROUND: Rabies is a highly fatal disease transmitted through the bite of a
rabid animal. Human deaths can be prevented by prompt administering of rabies
vaccine and rabies immunoglobulin following the exposure. An assessment of
community knowledge, awareness and practices on rabies is important during
outbreak to understand their preparedness and target educational messages and
response activities by the rapid response team. METHODS: A rabies outbreak has
occurred in Rangjung town, eastern Bhutan on 4 October 2016. A rapid response
team was activated to investigate outbreak and to establish a control program. A
community-based questionnaire survey was conducted from 20 to 21 October 2016 to
assess the community knowledge of rabies to guide outbreak preparedness and also
target educational messages and response activities by the RRT. RESULTS: A total
of 67 respondents were interviewed, of which 61% were female and 39% male. All
the respondents have heard of rabies (100%), have knowledge on source of rabies
(dog) and its mode of transmission in animals and humans. Most (61%) respondents
were aware and also indicated that they would wash the animal bite wound with
soap and water and seek medical care on the same day of exposure (100%). Majority
(94%) of the respondents have indicated that they would report to the government
agencies if they see any suspected rabid dogs in the community and suggested
various control measures for dog population management and rabies in Rangjung
including neutering procedure and mass dog vaccination. Although only few (10%)
of the respondents households owned dogs and cats, but 50% of them have indicated
that their dogs were allowed to roam outside the home premises posing risk of
contracting rabies through rabid dog bites. CONCLUSIONS: Although this study
indicates a high level of knowledge and awareness on rabies among the community,
there exists some knowledge gaps about rabies and therefore, an awareness
education should be focused on the source of rabies and rabies virus transmission
route to reduce public concern on nonexposure events thereby reducing the cost on
unnecessary postexposure treatment.
PMID- 28415973
TI - Effect of the PREPARE intervention on sexual initiation and condom use among
adolescents aged 12-14: a cluster randomised controlled trial in Dar es Salaam,
Tanzania.
AB - BACKGROUND: Unsafe sexual practices continue to put adolescents at risk for a
number of negative health outcomes in Tanzania. While there are some effective
theory-based intervention packages with positive impact on important mediators of
sexual behaviours, a context specific and tested intervention is urgently needed
in Tanzania. PURPOSE: To develop and evaluate an intervention that will have a
significant effect in reducing sexual initiation and promoting condom use among
adolescents aged 12-14 in Dar es Salaam, Tanzania. DESIGN: A school-based Cluster
Randomised Controlled Trial was conducted during 2011-2014 in Kinondoni
Municipality. METHODS: A total of 38 public primary schools were randomly
selected, of which half were assigned to the intervention and half to the control
group based on their size and geographic location. Participants were interviewed
using a self-administered questionnaire at baseline before the PREPARE
intervention and then, 6 and 12 months following intervention. The primary
outcomes were self-reported sex initiation and condom use during the past 6
months. Data analysis was done using Generalized Estimating Equation (GEE)
modelling controlling for repeated measures and clustering of students within
schools. RESULTS: A total of 5091 students were recruited at baseline, and
interviewed again at 6 (n = 4783) and 12 months (n = 4370). Mean age of
participants at baseline was 12.4 years. Baseline sociodemographic, psychometric
and behavioural characteristics did not significantly differ between the two
study arms. The GEE analysis indicated that the intervention had a significant
effect on sexual initiation in both sexes after controlling for clustering and
correlated repeated measures. A significantly higher level of action planning to
use condoms was reported among female adolescent in the intervention arm than
those in the control arm (p = 0.042). An effect on condom use behaviour was
observed among male adolescent (p = 0.004), but not among female (p = 0.463).
CONCLUSIONS: The PREPARE intervention had an effect in delaying self-reported
sexual initiation among adolescents aged 12-14 in Dar es Salaam Tanzania. The
intervention positively influenced action planning to use condoms for both sexes
and increased actual condom use among male adolescents only. Future interventions
addressing adolescent sexual and reproductive health should focus on impacting
mediators of behaviour change. TRIAL REGISTRATION: Australian New Zealand
Clinical Trials Registry ACTRN12613000900718 , registered on 13 August, 2013.
PMID- 28415974
TI - Evaluation of the association between quantitative mammographic density and
breast cancer occurred in different quadrants.
AB - BACKGROUND: To investigate the relationship between mammographic density measured
in four quadrants of a breast with the location of the occurred cancer. METHODS:
One hundred and ten women diagnosed with unilateral breast cancer that could be
determined in one specific breast quadrant were retrospectively studied. Women
with previous cancer/breast surgery were excluded. The craniocaudal (CC) and
mediolateral oblique (MLO) mammography of the contralateral normal breast were
used to separate a breast into 4 quadrants: Upper-Outer (UO), Upper-Inner (UI),
Lower-Outer (LO), and Lower-Inner (LI). The breast area (BA), dense area (DA),
and percent density (PD) in each quadrant were measured by using the fuzzy-C
means segmentation. The BA, DA, and PD were compared between patients who had
cancer occurring in different quadrants. RESULTS: The upper-outer quadrant had
the highest BA (37 +/- 15 cm2) and DA (7.1 +/- 2.9 cm2), with PD = 20.0 +/- 5.8%.
The order of BA and DA in the 4 separated quadrants were: UO > UI > LO > LI, and
almost all pair-wise comparisons showed significant differences. For tumor
location, 67 women (60.9%) had tumor in UO, 16 (14.5%) in UI, 7 (6.4%) in LO, and
20 (18.2%) in LI quadrant, respectively. The estimated odds and the 95%
confidence limits of tumor development in the UO, UI, LO and LI quadrants were
1.56 (1.06, 2.29), 0.17 (0.10, 0.29), 0.07 (0.03, 0.15), and 0.22 (0.14, 0.36),
respectively. In these 4 groups of women, the order of quadrant BA and DA were
all the same (UO > UI > LO > LI), and there was no significant difference in BA,
DA or PD among them (all p > 0.05). CONCLUSIONS: Breast cancer was most likely to
occur in the UO quadrant, which was also the quadrant with highest BA and DA; but
for women with tumors in other quadrants, the density in that quadrant was not
the highest. Therefore, there was no direct association between quadrant density
and tumor occurrence.
PMID- 28415975
TI - Ka-HOLO Project: a protocol for a randomized controlled trial of a native
cultural dance program for cardiovascular disease prevention in Native Hawaiians.
AB - BACKGROUND: As a major risk factor for cardiovascular and cerebrovascular disease
(CVD), hypertension affects 33% of U.S. adults. Relative to other US races and
ethnicities, Native Hawaiians have a high prevalence of hypertension and are 3 to
4 times more likely to have CVD. Effective, culturally-relevant interventions are
needed to address CVD risk in this population. Investigators of the Ka-HOLO
Project developed a study design to test the efficacy of an intervention that
uses hula, a traditional Hawaiian dance, to increase physical activity and reduce
CVD risk. METHODS: A 2-arm randomized controlled trial with a wait-list control
design will be implemented to test a 6-month intervention based on hula to manage
blood pressure and reduce CVD risk in 250 adult Native Hawaiians with diagnosed
hypertension. Half of the sample will be randomized to each arm, stratified
across multiple study sites. Primary outcomes are reduction in systolic blood
pressure and improvement in CVD risk as measured by the Framingham Risk Score.
Other psychosocial and sociocultural measures will be included to determine
mediators of intervention effects on primary outcomes. Assessments will be
conducted at baseline, 3 months, and 6 months for all participants, and at 12
months for intervention participants only. DISCUSSION: This trial will elucidate
the efficacy of a novel hypertension management program designed to reduce CVD
risk in an indigenous population by using a cultural dance form as its physical
activity component. The results of this culturally-based intervention will have
implications for other indigenous populations globally and will offer a
sustainable, culturally-relevant means of addressing CVD disparities. TRIAL
REGISTRATION: ClinicalTrials.gov: NCT02620709 , registration date November 23,
2015.
PMID- 28415976
TI - SMRT genome assembly corrects reference errors, resolving the genetic basis of
virulence in Mycobacterium tuberculosis.
AB - BACKGROUND: The genetic basis of virulence in Mycobacterium tuberculosis has been
investigated through genome comparisons of virulent (H37Rv) and attenuated
(H37Ra) sister strains. Such analysis, however, relies heavily on the accuracy of
the sequences. While the H37Rv reference genome has had several corrections to
date, that of H37Ra is unmodified since its original publication. RESULTS: Here,
we report the assembly and finishing of the H37Ra genome from single-molecule,
real-time (SMRT) sequencing. Our assembly reveals that the number of H37Ra
specific variants is less than half of what the Sanger-based H37Ra reference
sequence indicates, undermining and, in some cases, invalidating the conclusions
of several studies. PE_PPE family genes, which are intractable to commonly-used
sequencing platforms because of their repetitive and GC-rich nature, are
overrepresented in the set of genes in which all reported H37Ra-specific variants
are contradicted. Further, one of the sequencing errors in H37Ra masks a true
variant in common with the clinical strain CDC1551 which, when considered in the
context of previous work, corresponds to a sequencing error in the H37Rv
reference genome. CONCLUSIONS: Our results constrain the set of genomic
differences possibly affecting virulence by more than half, which focuses
laboratory investigation on pertinent targets and demonstrates the power of SMRT
sequencing for producing high-quality reference genomes.
PMID- 28415977
TI - Perspectives of Frailty and Frailty Screening: Protocol for a Collaborative
Knowledge Translation Approach and Qualitative Study of Stakeholder
Understandings and Experiences.
AB - BACKGROUND: Accompanying the unprecedented growth in the older adult population
worldwide is an increase in the prevalence of frailty, an age-related clinical
state of increased vulnerability to stressor events. This increased vulnerability
results in lower social engagement and quality of life, increased dependency, and
higher rates of morbidity, health service utilization and mortality. Early
identification of frailty is necessary to guide implementation of interventions
to prevent associated functional decline. Consensus is lacking on how to
clinically recognize and manage frailty. It is unknown how healthcare providers
and healthcare consumers understand and perceive frailty, whether or not they
regard frailty as a public health concern; and information on the indirect and
direct experiences of consumer and healthcare provider groups towards frailty are
markedly limited. METHODS: We will conduct a qualitative study of consumer,
practice nurse, general practitioner, emergency department physician, and
orthopedic surgeons' perspectives of frailty and frailty screening in
metropolitan and non-metropolitan South Australia. We will use tailored
combinations of semi-structured interviews and arts-based data collection methods
depending on each stakeholder group, followed by inductive and iterative analysis
of data using qualitative description. DISCUSSION: Using stakeholder driven
approaches to understanding and addressing frailty and frailty screening in
context is critical as the prevalence and burden of frailty is likely to increase
worldwide. We will use the findings from the Perceptions of Frailty and Frailty
Screening study to inform a context-driven identification, implementation and
evaluation of a frailty-screening tool; drive awareness, knowledge, and skills
development strategies across stakeholder groups; and guide future efforts to
embed emerging knowledge about frailty and its management across diverse South
Australian contexts using a collaborative knowledge translation approach. Study
findings will help achieve a coordinated frailty and healthy ageing strategy with
relevance to other jurisdictions in Australia and abroad, and application of the
stakeholder driven approach will help illuminate how its applicability to other
jurisdictions.
PMID- 28415978
TI - Bacterial communities and metabolic activity of faecal cultures from equol
producer and non-producer menopausal women under treatment with soy isoflavones.
AB - BACKGROUND: Isoflavones are polyphenols with estrogenic activity found mainly in
soy and soy-derived products that need to be metabolised in the intestine by the
gut bacteria to be fully active. There is little knowledge about isoflavone
bioconversion and equol production in the human intestine. In this work, we
developed an in vitro anaerobic culture model based on faecal slurries to assess
the impact of isoflavone supplementation on the overall intestinal bacterial
composition changes and associated metabolic transformations. RESULTS: In the
faecal anaerobic batch cultures of this study bioconversion of isoflavones into
equol was possible, suggesting the presence of viable equol-producing bacterial
taxa within the faeces of menopausal women with an equol producer phenotype. The
application of high-throughput DNA sequencing of 16S rRNA gene amplicons revealed
the composition of the faecal cultures to be modified by the addition of
isoflavones, with enrichment of some bacterial gut members associated with the
metabolism of phenolics and/or equol production, such as Collinsella,
Faecalibacterium and members of the Clostridium clusters IV and XIVa. In
addition, the concentration of short-chain fatty acids (SCFAs) detected in the
isoflavone-containing faecal cultures was higher in those inoculated with faecal
slurries from equol-producing women. CONCLUSIONS: This study constitutes the
first step in the development of a faecal culturing system with isoflavones that
would further allow the selection and isolation of intestinal bacterial types
able to metabolize these compounds and produce equol in vitro. Although limited
by the low number of faecal cultures analysed and the inter-individual bacterial
diversity, the in vitro results obtained in this work tend to indicate that soy
isoflavones might provide an alternative energy source for the increase of equol
producing taxa and enhancement of SCFAs production. SCFAs and equol are both
considered pivotal bacterial metabolites in the triggering of intestinal health
related beneficial effects.
PMID- 28415979
TI - Behavioral activation for smoking cessation and mood management following a
cardiac event: results of a pilot randomized controlled trial.
AB - BACKGROUND: Smoking cessation following hospitalization for Acute Coronary
Syndrome (ACS) significantly reduces subsequent mortality. Depressed mood is a
major barrier to cessation post-ACS. Although existing counseling treatments
address smoking and depression independently in ACS patients, no integrated
treatment addresses both. We developed an integrated treatment combining gold
standard cessation counseling with behavioral activation-based mood management;
Behavioral Activation Treatment for Cardiac Smokers (BAT-CS). The purpose of this
pilot randomized controlled trial was to test feasibility, acceptability, and
preliminary efficacy of BAT-CS vs. Standard of Care (SC). METHODS: Participants
were recruited during hospitalization for ACS and were randomly assigned to BAT
CS or SC. The nicotine patch was offered in both conditions. Smoking, mood, and
stress outcomes were collected at end-of-treatment and 24-week follow-up.
RESULTS: Fifty-nine participants (28 BAT-CS, 31 SC) were recruited over 42 weeks,
and assessment completion was above 80% in both conditions. Treatment
acceptability and fidelity were high. At 24 week follow-up adjusted odds ratios
favoring BAT-CS were 1.27 (95% CI: 0.41-3.93) for 7-day point prevalence
abstinence and 1.27 (95% CI: 0.42-3.82) for continuous abstinence. Time to first
smoking lapse was significantly longer in BAT-CS (62.4 vs. 31.8 days, p = 0.03).
At 24-weeks, effect sizes for mood and stress outcomes ranged from eta2partial
of.07-.11, with significant between treatment effects for positive affect,
negative affect, and stress. CONCLUSIONS: The design of this study proved
feasible and acceptable. Results provide preliminary evidence that combining
behavioral activation with standard smoking cessation counseling could be
efficacious for this high risk population. A larger trial with longer follow-up
is warranted. TRIAL REGISTRATION: NCT01964898 . First received by
clinicaltrials.gov October 15, 2013.
PMID- 28415980
TI - The effects of bending speed on the lumbo-pelvic kinematics and movement pattern
during forward bending in people with and without low back pain.
AB - BACKGROUND: Impaired lumbo-pelvic movement in people with low back pain during
bending task has been reported previously. However, the regional mobility and the
pattern of the lumbo-pelvic movement were found to vary across studies. The
inconsistency of the findings may partly be related to variations in the speed at
which the task was executed. This study examined the effects of bending speeds on
the kinematics and the coordination lumbo-pelvic movement during forward bending,
and to compare the performance of individuals with and without low back pain.
METHODS: The angular displacement, velocity and acceleration of the lumbo-pelvic
movement during the repeated forward bending executed at five selected speeds
were acquired using the three dimensional motion tracking system in seventeen
males with low back pain and eighteen males who were asymptomatic. The regional
kinematics and the degree of coordination of the lumbo-pelvic movement during
bending was compared and analysed between two groups. RESULTS: Significantly
compromised performance in velocity and acceleration of the lumbar spine and hip
joint during bending task at various speed levels was shown in back pain group (p
< 0.01). Both groups displayed a high degree of coordination of the lumbo-pelvic
displacement during forward bending executed across the five levels of speed
examined. Significant between-group difference was revealed in the coordination
of the lumbo-pelvic velocity and acceleration (p < 0.01). Asymptomatic group
moved with a progressively higher degree of lumbo-pelvic coordination for
velocity and acceleration while the back pain group adopted a uniform lumbo
pelvic pattern across all the speed levels examined. CONCLUSIONS: The present
findings show that bending speed imposes different levels of demand on the
kinematics and pattern of the lumbo-pelvic movement. The ability to regulate the
lumbo-pelvic movement pattern during the bending task that executed at various
speed levels was shown only in pain-free individuals but not in those with low
back pain. Individuals with low back pain moved with a stereotyped strategy at
their lumbar spine and hip joints. This specific aberrant lumbo-pelvic movement
pattern may have a crucial role in the maintenance of the chronicity in back
pain.
PMID- 28415981
TI - Progress in vaccination towards hepatitis B control and elimination in the Region
of the Americas.
AB - BACKGROUND: Over recent decades, the Region of the Americas has made significant
progress towards hepatitis B elimination. We summarize the countries/territories'
efforts in introducing and implementing hepatitis B (HB) vaccination and in
evaluating its impact on HB virus seroprevalence. METHODS: We collected
information about HB vaccination schedules, coverage estimates, and year of
vaccine introduction from countries/territories reporting to the Pan American
Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF
Joint Reporting Form on Immunization. We obtained additional information
regarding countries/territories vaccination recommendations and strategies
through communications with Expanded Program on Immunization (EPI) managers and
national immunization survey reports. We identified vaccine impact studies
conducted and published in the Americas. RESULTS: As of October 2016, all 51
countries/territories have included infant HB vaccination in their official
immunization schedule. Twenty countries, whose populations represent over 90% of
the Region's births, have included nationwide newborn HB vaccination. We
estimated at 89% and 75%, the regional three-dose series and the birth dose HB
vaccination coverage, respectively, for 2015. The impact evaluations of infant HB
immunization programs in the Region have shown substantial reductions in HB
surface antigen (HBsAg) seroprevalence. CONCLUSION: The achievements of
vaccination programs in the Americas suggest that the elimination of perinatal
and early childhood HB transmission could be feasible in the short-term.
Moreover, the data gathered indicate that the Region may have already achieved
the 2020 WHO goal for HB control.
PMID- 28415982
TI - The treatment of primary mediastinal large B-cell lymphoma: a two decades
monocentric experience with 98 patients.
AB - BACKGROUND: The purpose of this study is to investigate the most suitable first
line approach and the best combination treatment for primary mediastinal large B
cell lymphoma (PMLBCL) as they have been matter of debate for at least two
decades. METHODS: Our single centre experience in the treatment of 98 de novo
PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B
chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy;
30 were irradiated after chemotherapy, although not receiving rituximab and 20
received rituximab without radiotherapy consolidation. Eleven patients received
chemotherapy only. RESULTS: Sixty-one (62.2%) patients achieved a complete
response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial
responders, 21 obtained a complete response after radiotherapy. At the end of
their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial
response (6.1%). Eleven patients relapsed within the first 2 years of follow-up.
The 17-year overall survival is 72.0% (15 patients died); progression-free and
disease-free survival are 67.6% and 88.4%, respectively. A statistically
significant difference in overall and progression-free survival was noted among
treatment groups, although no disease-free survival difference was documented.
CONCLUSIONS: Our data indicate that a third-generation regimen like MACOP-B could
be considered a suitable first-line treatment. Mediastinal consolidation
radiotherapy impacts on survival and complete response rates and remains a good
strategy to convert partial into complete responses. Data suggest that
radiotherapy may be avoided in patients obtaining a complete response after
(immuno)chemotherapy, but this requires confirmation with further ad hoc studies.
PMID- 28415983
TI - Exhaled carbon monoxide: a non-invasive biomarker of short-term exposure to
outdoor air pollution.
AB - BACKGROUND: In urban settings of Africa with rapidly increasing population,
traffic-related air pollution is a major contributor to outdoor air pollution
(OAP). Although OAP has been identified as a leading cause of global morbidity
and mortality, there is however, lack of a simple biomarker to assess levels of
exposure to OAP in resource-poor settings. This study evaluated the role of
exhaled carbon monoxide (exhCO) as a potential biomarker of exposure to ambient
carbon monoxide (ambCO) from OAP. METHODS: This was a descriptive study conducted
among male commercial motorcycle riders in Cotonou - the economic capital of
Benin. The participants' AmbCO was measured using a portable carbon monoxide (CO)
data logger for 8 h during the period of their shift. ExhCO was measured just
before and immediately after their shift (8-h) Participants were asked not to
cook or to smoke during the day of the measurements. Linear regression analysis
was used to assess the association between ambCO and exhCO for the last 2, 4 and
6 h of their shift. RESULTS: Of 170 participants who completed the study, their
mean +/- SD age was 42.2 +/- 8.4 years, and their mean +/- SD daily income was
7.3 +/- 2.7$. Also, 95% of the participants' used solid fuels for cooking and
only 2% had ever smoked. Average exhCO increased by 5.1 ppm at the end of the
shift (p = 0.004). Post-shift exhCO was significantly associated to ambCO, this
association was strongest for the last 2 h of OAP exposure before exhCO
measurement (beta = 0.34, p < 0.001). CONCLUSION: ExhCO level was associated with
recent exposure to ambCO from OAP with measurable increase after 8 h of exposure.
These findings suggest that ExhCO may be a potential biomarker of short-term
exposure to OAP.
PMID- 28415984
TI - Comparison of three different methods for risk adjustment in neonatal medicine.
AB - BACKGROUND: Quality improvement in health care requires identification of areas
in need of improvement by comparing processes and patient outcomes within and
between health care providers. It is critical to adjust for different case-mix
and outcome risks of patient populations but it is currently unclear which
approach has higher validity and how limitations need to be dealt with. Our aim
was to compare 3 approaches towards risk adjustment for 7 different major quality
indicators in neonatal intensive care (21 models). METHODS: We compared an
indirect standardization, logistic regression and multilevel approach. Parameters
for risk adjustment were chosen according to literature and the condition that
they may not depend on processes performed by treating clinics. Predictive
validity was tested using the mean Brier Score and by comparing area under curve
(AUC) using high quality population based data separated into training and
validation sets. Changes in attributional validity were analysed by comparing the
effect of the models on the observed-to-expected ratios of the clinics in
standardized mortality/morbidity ratio charts. RESULTS: Risk adjustment based on
indirect standardization revealed inferior c-statistics but superior Brier scores
for 3 of 7 outcomes. Logistic regression and multilevel modelling were equivalent
to one another. C-statistics revealed that predictive validity was high for 8 and
acceptable for 11 of the 21 models. Yet, the effect of all forms of risk
adjustment on any clinic's comparison with the standard was small, even though
there was clear risk heterogeneity between clinics. CONCLUSIONS: All three
approaches to risk adjustment revealed comparable results. The limited effect of
risk adjustment on clinic comparisons indicates a small case-mix influence on
observed outcomes, but also a limited ability to isolate quality improvement
potential based on risk-adjustment models. Rather than relying on methodological
approaches, we instead recommend that clinics build small collaboratives and
compare their indicators both in risk-adjusted and unadjusted form together. This
allows qualitatively investigating and discussing the residual risk-differences
within networks. The predictive validity should be quantified and reported and
stratification into risk groups should be more widely used to correct for
confounding.
PMID- 28415985
TI - Vitamin D-related gene polymorphism predict treatment response to pegylated
interferon-based therapy in Thai chronic hepatitis C patients.
AB - BACKGROUND: Patients with chronic hepatitis C (HCV) infection have high
prevalence of vitamin D deficiency. Genome-wide association study data has showed
that several genetic variants within vitamin D cascade affect vitamin D function.
This study aimed to determine whether genetic polymorphisms of genes in the
vitamin D pathway are associated with treatment responses to pegylated interferon
(PEG-IFN)-based therapy in patients with chronic HCV infection. METHODS: The
study included 623 Thai patients from 2 university hospitals diagnosed with
chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients
were genotyped for functional variants on vitamin D synthetic pathway including
GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1
(rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained
virologic response (SVR) at 24 weeks following discontinuation of therapy were
identified using a logistic regression analysis. RESULTS: SVR was achieved by
60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In
44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the
DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who
had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele
(59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR
rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG
allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0-1 (OR = 5.00;
95% CI, 2.02-12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95%
CI, 1.03-7.05; P = 0.04) were independent pre-treatment predictors of SVR
following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA <
400,000 IU/ml (OR = 1.96; 95% CI, 1.13-3.39; P = 0.02) was the only independent
predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1
and CYP27B1 were not associated with treatment outcome even in genotype 1 or non
genotype 1 HCV infection. CONCLUSION: The DHCR7 polymorphism may be a pre
treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV
genotype 1 infection.
PMID- 28415986
TI - Detection of CTX-M-15 beta-lactamases in Enterobacteriaceae causing hospital- and
community-acquired urinary tract infections as early as 2004, in Dar es Salaam,
Tanzania.
AB - BACKGROUND: The spread of Extended Spectrum beta-lactamases (ESBLs) among
Enterobacteriaceae and other Gram-Negative pathogens in the community and
hospitals represents a major challenge to combat infections. We conducted a study
to assess the prevalence and genetic makeup of ESBL-type resistance in bacterial
isolates causing community- and hospital-acquired urinary tract infections.
METHODS: A total of 172 isolates of Enterobacteriaceae were collected in Dar es
Salaam, Tanzania, from patients who met criteria of community and hospital
acquired urinary tract infections. We used E-test ESBL strips to test for ESBL
phenotype and PCR and sequencing for detection of ESBL genes. RESULTS: Overall
23.8% (41/172) of all isolates were ESBL-producers. ESBL-producers were more
frequently isolated from hospital-acquired infections (32%, 27/84 than from
community-acquired infections (16%, 14/88, p < 0.05). ESBL-producers showed high
rate of resistance to ciprofloxacin (85.5%), doxycycline (90.2%), gentamicin
(80.5%), nalidixic acid (84.5%), and trimethoprim-sulfamethoxazole (85.4%).
Furthermore, 95% of ESBL-producers were multi-drug resistant compared to 69% of
non-ESBL-producers (p < 0.05). The distribution of ESBL genes were as follows:
29/32 (90.6%) bla CTX-M-15, two bla SHV-12, and one had both bla CTX-M-15 and bla
SHV-12. Of 29 isolates carrying bla CTX-M-15, 69% (20/29) and 31% (9/29) were
hospital and community, respectively. Bla SHV-12 genotypes were only detected in
hospital-acquired infections. CONCLUSION: bla CTX-M-15 is a predominant gene
conferring ESBL-production in Enterobacteriaceae causing both hospital- and
community-acquired infections in Tanzania.
PMID- 28415987
TI - Validity and reliability of fluoroscopy for digital radiography: a new way to
evaluate diaphragmatic mobility.
AB - BACKGROUND: Fluoroscopy is considered the most accurate method to evaluate the
diaphragm, yet most existing methods for measuring diaphragmatic mobility using
fluoroscopy are complex. To assess the validity and reliability of a new
evaluation method of diaphragmatic motion using fluoroscopy by digital
radiography of healthy adults. METHODS: Twenty-six adults were evaluated,
according to the parameters: anthropometry and pulmonary function test. The
evaluation of diaphragm mobility by means of fluoroscopy by digital radiography
method was randomly conducted by two raters (A and B). The Pearson correlation
coefficient and the intraclass correlation coefficient (ICC) were used to assess
the concurrent validity. The inter-rater and intra-rater reliability of the
measurement of diaphragmatic motion was determined using ICC and a confidence
interval of 95%. RESULTS: There was a relationship in the assessment of the
concurrent validity. There was good inter-rater reliability for right
hemidiaphragm mobility and moderate reliability for left hemidiaphragm in the
first assessment. In the second assessment, there was good reliability for the
mobility of both hemidiaphragms. There was good intra-rater reliability in the
mobility of both hemidiaphragms for raters A and B. CONCLUSION: The evaluation of
diaphragmatic motion using fluoroscopy by digital radiography proved to be a
valid and reliable method of healthy adults.
PMID- 28415988
TI - The efficacy and safety of mivacurium in pediatric patients.
AB - BACKGROUND: Mivacurium is the shortest acting nondepolarizing muscle relaxant
currently available; however, the effect of different dosages and injection times
of intravenous mivacurium administration in children of different ages has rarely
been reported. This study was aimed to evaluate the muscle relaxant effects and
safety of different mivacurium dosages administered over different injection
times in pediatric patients. METHODS: Six hundred forty cases of pediatric
patients, aged 2 m-14 years, ASA I or II, were divided into four groups (Groups
A, B, C, D) according to the age class (2-12 m, 13-35 m, 3-6 years and 7-14
years) respectively, also each group were divided into four subgroups by
induction dose (0.15, 0.2 mg/kg in 2-12 m age class; 0.2, 0.25 mg/kg in other
three age classes), and mivacurium injection time (20 s, 40 s), totally 16
subgroups. Neuromuscular transmission was monitored with supramaximal train-of
four stimulation of the ulnar nerve. Radial artery blood (1 ml) was sampled to
quantify plasma histamine concentrations before and 1, 4, and 7 min after
mivacurium injection (P0, P1, P2 and P3). RESULTS: Five hundred sixty-two cases
completed the study. There were no demographic differences within the four
groups. The onset time of 0.2 mg/kg groups in 2-12 m aged patients were shorter
than those of 0.15 mg/kg groups (189 +/- 64 s vs. 220 +/- 73 s, 181 +/- 60 s vs.
213 +/- 71 s, P <0.05), and the recovery times were no statistical differences.
The T1 25% recovery time of 0.2 mg/kg in 3-6 years aged patients was shorter than
that of 0.25 mg/kg group (693 +/- 188 s vs. 800 +/- 206 s, P <0.05). The onset
and recovery times of mivacurium were not different in 13-35 m and 7-14 years
aged patients. The plasma concentrations of histamine at P0, P1, P2 and P3 were
not different within four groups. CONCLUSIONS: The induction dose and injection
time of mivacurium had mostly insignificant effects on onset and recovery times.
The main exception to this was that in 2-12 m aged patients, increasing the dose
of mivacurium from 0.15 to 0.2 mg/kg accelerated the onset time by about 30 s.
Mivacurium produced no significant release of histamine in any age group at the
doses studied. TRIAL REGISTRATION: ClinicalTrials.gov Identifier- NCT02117401 ,
July 14, 2014. (Retrospectively registered).
PMID- 28415989
TI - Evaluation of genotype MTBDRplus VER 2.0 line probe assay for the detection of
MDR-TB in smear positive and negative sputum samples.
AB - BACKGROUND: Multi drug resistant tuberculosis (MDR-TB) poses formidable
challenges to TB control due to its complex diagnostic and treatment challenges
and often associated with a high rate of mortality. Accurate and rapid detection
of MDR-TB is critical for timely initiation of treatment. Line Probe Assay (LPA)
is a qualitative in vitro diagnostic test based on DNA-STRIP technology for the
identification of the M. tuberculosis complex and its resistance to rifampicin
(RMP) and/or isoniazid (INH). Hain Lifescience, GmbH, Germany has improved the
sensitivity of Genotype MTBDRplus VER 2.0 LPA for the detection of MDR-TB; with
the possibility of applying the tool in smear negative sputum samples. METHOD: A
cross sectional study was conducted on 274 presumptive MDR-TB patients referred
to the National TB Reference Laboratory (NTRL), Ethiopian Public Health Institute
(EPHI) who submitted sputum samples for laboratory diagnosis of drug resistant-TB
testing. Seventy-two smear and culture positive samples processed in smear
positive direct LPA category and 197 smear negative sputum samples were processed
for direct LPA. Among the smear negative samples 145 (73.6%) were culture
negative and 26 (13.2%) were culture positive. All specimens were processed using
NALC-NaOH method and ZN smear microscopy done from sediments. Genotype MTBDRplus
VER 2.0 done from processed sputum sediments and the result was compared against
the reference, BACTEC MGIT 960 culture and DST. Sensitivity, specificity, PPV and
NPV of Genotype MTBDRplus VER 2.0 assay was determined and P-value <0.05 was
considered as statistically significant. RESULTS: The sensitivity, specificity,
PPV and NPV of Genotype MTBDRplus VER 2.0 LPA were 96.4, 100, 100 and 96.9%,
respectively for the detection of MDR-TB from direct smear positive sputum
samples. The sensitivity, specificity, PPV and NPV of Genotype MTBDR plus VER 2.0
LPA were 77.8, 97.2, 82.4 and 97.2%, respectively, for the detection of M.
tuberculosis from direct smear negative sputum samples. Fourteen (53.8%) samples
had valid results with LPA among the 26 smear negative culture positive samples.
The remaining 8 (30.8%) and 4 (15.4%) were invalid and negative with LPA,
respectively. The sensitivity and specificity of Genotype MTBDRplus VER 2.0 LPA
were 100% for the detection of MDR-TB among 14 direct smear negative and culture
positive sputum samples. The most common mutations associated with RMP and INH
resistance were S531L and S315TL, respectively. A single rare mutation
(C15T/A16G) was detected for INH resistance. CONCLUSION: The diagnostic
performance of Genotype MTBDRplus VER 2.0 LPA in direct smear positive sputum
sample was highly sensitive and specific for early detection of MDR-TB. However,
the diagnostic performance of this molecular assay in direct smear negative
sputum sample was low and showed a high level of invalid results for detection of
M. tuberculosis and its resistance to RMP and/or INH so it is unlikely to
implement Genotype MTBDRplus VER 2.0 for the detection of MDR-TB in direct smear
negative sample in our routine settings. The sensitivity of the assay should be
improved for detection of MDR-TB in direct smear negative sputum specimens.
PMID- 28415990
TI - Prognostic value of pretreatment standardized uptake value of F-18
fluorodeoxyglucose PET in patients with gastric cancer: a meta-analysis.
AB - BACKGROUND: F-18- fluorodeoxyglucose Positron emission tomography (18FDG-PET) has
been widely used in clinical practice. However, the prognostic value of the
pretreatment standardized uptake value (SUV) for patients with gastric cancer
remains controversial. METHODS: Major databases were systematically searched. The
quality of the included studies was assessed using the Newcastle-Ottawa scale;
the PET protocols were also evaluated. The pooled hazard ratio (HR) for overall
survival (OS) and recurrence-free survival (RFS) were used to estimate the effect
size. Data from the included studies were analyzed using Review Manager Software
version 5.2. RESULTS: Eight studies with 1080 patients were included. The pooled
HR for OS of six studies including 672 patients was 1.72 (95% CI [1.28-2.3], p =
0.0004, I2 = 0%), indicating that patients with high SUVs may have poor
prognosis. The pooled HR for RFS was 1.70 (95% CI [1.20-2.39], p = 0.003, I2 =
0%). Subgroup analysis based on the cutoff values determining method indicated
that the receiver operating characteristic (ROC) method could better define the
cutoff value. Subgroup analysis based on the therapeutic strategies used
subsequently indicated the significant prognostic value of SUV. CONCLUSION: In
conclusion, our meta-analysis indicated that pretreatment SUV in primary lesions
can be an important prognostic factor for overall survival and recurrence-free
survival in patients with gastric cancer. High SUVs may indicate poor prognosis.
PMID- 28415991
TI - Clinical patient registry recruitment and retention: a survey of patients in two
chronic disease registries.
AB - BACKGROUND: The collection of routine clinical data in the setting of research
registries can serve an important role in understanding real world care. However,
relatively little is known about the patient experience in registries, motivating
us to survey patients enrolled in two chronic disease registries. METHODS: We
conducted similar surveys in two disease-based registries based at one academic
medical center in the US. One group of patients with rheumatoid arthritis (RA)
had been enrolled in a registry, and we focused on retention factors. In a second
group of patients with inflammatory bowel disease (IBD) recently enrolled or
considering enrollment, we examined factors that would influence their enrollment
and willingness to answer frequent questionnaires and give biospecimens. The
surveys were analyzed using descriptive statistics and the two cohorts were
compared using nonparametric and chi-square tests. RESULTS: We received 150 (50%)
completed surveys from RA and 169 (63%) from IBD patients. Mean age of subjects
was 62 years in RA and 43 in IBD with more women respondents with RA (83%) than
IBD (62%). The two groups described very similar factors as the top three
motivations for participation: desire to help others, desire to improve care of
own disease, and ease of volunteering. Preferred methods of surveying included
mail, e-mail, but telephone was not favored; age was an important correlate of
this preference. Respondents preferred surveys either every 1-3 months (28.7% RA
and 55.0% IBD) or every 4-6 months (50.7% RA and 29.0% IBD). They differed in the
preference for payment for answering surveys with 68.0% with RA answering that no
payment was necessary but only 36.1% with IBD felt similarly. CONCLUSIONS:
Patients engaged in clinical registries demonstrate a high level of commitment to
improve care and many report a willingness to answer questions relatively
frequently.
PMID- 28415993
TI - Moving to business - changes in physical activity and sedentary behavior after
multilevel intervention in small and medium-size workplaces.
AB - BACKGROUND: Regular physical activity (PA) promotes and excessive sedentary
behavior (SB) deteriorates health. Yet the Finnish working-aged population spends
most of the day sitting. A 1-year Moving To Business (MTB) -intervention
supported small and medium-size workplaces to combat sedentariness. This paper
reports the changes in employees' PA and SB from before MTB (baseline) to 1 year
after baseline (follow-up). METHODS: Twelve workplaces with a total of 396
employees participated. Each workplace nominated a team to promote PA and reduce
SB at organizational, working unit and employee level. The teams were mentored
regionally through meetings, workshop and tools. Changes in PA and SB were
assessed with a questionnaire and an accelerometer. Wald Confidence Interval (Cl)
for a difference of proportions with matched pairs was used in the questionnaire
data (%-points with 95% CI) and linear mixed model in the accelerometer data
(minutes and % of wear-time with 95% CI). RESULTS: The mean age of the
respondents to the questionnaire (N = 296; 75%) was 42.6 (SD 10.9), 64% were
women, 95% had some education after high school, 74% worked in the day shift, 71%
did sedentary work and 51% were overweight. The mean number of actions
implemented in the workplaces was 6.8 and the multilevel approach was fully
applied in 6 workplaces. Based on the questionnaire the time spent in SB
decreased from baseline to follow-up 16% (95% CI -29 to -3) in total and 22% (-41
to -3) at work. The accelerometer showed daily increases of 33.7 min (15.3 to
52.1) and 6.8% (3.1 to 10.4) in total PA, 30.9 min (15.3 to 46.5) and 6.1% (2.9
to 9.2) in light PA and 673 (209 to 1139) more steps at work. Daily SB at work
decreased 44.9 min (-68.0 to -21.8) and 7.6% (-11.9 to -3.2). Daily leisure PA
declined 11.0 min (-24.9 to 2.9) and 3.2% (-6.2 to -0.2). Number of levels or
actions had no effect on changes. CONCLUSIONS: Employees' PA increased and SB
reduced at work during the intervention. At the same time leisure PA decreased
slightly. Workplaces can achieve meaningful changes in employees' PA and SB if
assisted systematically. Controlled studies are needed to confirm the present
findings. TRIAL REGISTRATION: NCT01999205 , registration date 11/01/2013.
PMID- 28415994
TI - A pathological and clinical study of 706 primary tumours of the ovary in the
largest tertiary hospital in Ghana.
AB - BACKGROUND: Ovarian tumours are a leading cause of death in Ghana. Even though
geographical and racial differences exist in the frequency, types and age
distribution of primary ovarian tumours, information about the clinical and
pathological characteristics of ovarian tumours in Ghana and its neighboring
countries is scanty. We determined the frequency, age distribution,
histopathological types and clinical features of primary ovarian tumours
diagnosed at the Korle-Bu Teaching Hospital in Ghana to aid in the management of
patients. METHOD: All pathology records of ovarian tumours diagnosed from January
2001 to December 2010 were reviewed. Histopathologically, tumours were classified
according to the then World Health Organization 1999 classification. Biographical
and clinical data of patients were also collected and entered into Epi-info to
determine the frequency, age distribution and other clinical features of the
types of ovarian tumour. RESULTS: Seven hundred and six ovarian tumours were
studied. Germ cell tumours were the most common (41.9%), with mean age of
occurrence being 30.7 years (SD 12.7), they were dominated by mature teratomas
(39.2%). Surface epithelial tumours were second, and commonly occurred in women
aged 35-44years, 77 (26.8%). Sex cord stromal tumours followed with mean age of
occurrence of 40.2 years (SD 17.9). The most common malignant tumours were
surface epithelial (52.1%) dominated by serous carcinomas with mean age 50.1
years. Most patients (47.7%) presented within 1 month of onset of symptoms,
feeling a lower abdominal mass (38.5%). CONCLUSION: The most common primary
ovarian tumours in this study are Germ cell tumours, dominated by mature
teratomas. Adenocarcinomas are mostly serous and occur in younger women compared
to findings of other Western studies. The single most common malignant ovarian
tumour in children and adolescents is Burkitt lymphoma. Patients who develop
ovarian tumours have no specific symptoms or signs at presentation, to aid early
diagnosis.
PMID- 28415992
TI - Women Epidemiology Lung Cancer (WELCA) study: reproductive, hormonal,
occupational risk factors and biobank.
AB - BACKGROUND: Lung cancer aetiology and clinical aspects have been mainly studied
in men, although specific risk factors probably exist in women. Here we present
the rationale, design and organization of the WELCA study (Women Epidemiology
Lung CAncer) that has been launched to investigate lung cancer in women, focusing
particularly on hormonal and occupational factors. METHODS/DESIGN: WELCA is a
population based case-control study and planned to recruit 1000 cases and 1000
controls in three years, based on study power calculation. Eligible cases are
female patients newly diagnosed with lung cancer, living in Paris and the Ile de
France area and aged up to 75 years. Almost all Parisian pneumology and oncology
clinical departments are involved. The control group is a random sample of the
population living in the same area, frequency-matched on age and additionally
stratified on the distribution of socio-professional categories of women residing
there. After acquisition of written consent, research nurses administer
standardized computer assisted questionnaires to all the subjects in face-to-face
interviews and acquire anthropometric measures. Besides usual socio-demographic
characteristics, information is gathered about menstrual and reproductive
factors, hormonal treatments, lifestyle and leisure characteristics, occupational
history, personal and familial medical history. Biological samples are also
collected, in order to establish a biobank for molecular epidemiology studies.
Molecular characteristics of the tumours will be obtained and patients will be
followed up for five years. DISCUSSION: The WELCA study aims to answer key
questions in lung cancer aetiology and clinical characteristics specifically in
women. The role of hormonal impregnation is investigated, and the interactions
with cigarette smoking or body mass index (BMI) will be analyzed in detail. The
occupational history of the subjects is carefully reconstructed, focusing in
particular on the service sector. The creation of a biobank for collection of
serum, plasma, DNA and tumour tissue will allow the genetic and biochemical
characterization of both the subjets and the tumours. The follow-up of the
patients will help in disentangling the role of hormonal factors and tumour
molecular characteristics in survival.
PMID- 28415995
TI - Type I interferon signaling is required for the APOBEC3/Rfv3-dependent
neutralizing antibody response but not innate retrovirus restriction.
AB - BACKGROUND: APOBEC3/Rfv3 restricts acute Friend retrovirus (FV) infection and
promotes virus-specific neutralizing antibody (NAb) responses. Classical Rfv3
studies utilized FV stocks containing lactate-dehydrogenase elevating virus
(LDV), a potent type I interferon inducer. Previously, we showed that APOBEC3 is
required for the anti-FV activity of exogenous IFN-alpha treatment. Thus, type I
interferon receptor (IFNAR) signaling may be required for the APOBEC3/Rfv3
response. RESULTS: To test if the APOBEC3/Rfv3 response is dependent on type I
IFN signaling, we infected IFNAR knockout versus IFNAR/APOBEC3 double-knockout
mice with FV/LDV or LDV-free FV, and evaluated acute FV infection and subsequent
NAb titers. We show that LDV co-infection and type I IFN signaling are not
required for innate APOBEC3-mediated restriction. By contrast, removal of LDV
and/or type I IFN signaling abrogated the APOBEC3-dependent NAb response.
CONCLUSIONS: APOBEC3 can restrict retroviruses in a type I IFN-independent manner
in vivo. By contrast, the ability of APOBEC3 to promote NAb responses is type I
IFN-dependent. These findings reveal novel insights on the interplay between type
I IFNs and APOBEC3 in vivo that may have implications for augmenting
antiretroviral NAb responses.
PMID- 28415996
TI - Travel and the emergence of high-level drug resistance in Plasmodium falciparum
in southwest Uganda: results from a population-based study.
AB - BACKGROUND: The I164L mutation on the dhfr gene confers high level resistance to
sulfadoxine-pyrimethamine (SP) but it is rare in Africa except in a cluster of
reports where prevalence >10% in highland areas of southwest Uganda and eastern
Rwanda. The occurrence of the dhfr I164L mutation was investigated in community
surveys in this area and examined the relationship to migration. METHODS: A cross
sectional prevalence survey was undertaken in among villages within the catchment
areas of two health facilities in a highland site (Kabale) and a highland fringe
site (Rukungiri) in 2007. Sociodemographic details, including recent migration,
were collected for each person included in the study. A total of 206 Plasmodium
falciparum positive subjects were detected by rapid diagnostic test; 203 in
Rukungiri and 3 in Kabale. Bloodspot samples were taken and were screened for
dhfr I164L. RESULTS: Sequence analysis confirmed the presence of the I164L
mutations in twelve P. falciparum positive samples giving an estimated prevalence
of 8.6% in Rukungiri. Of the three parasite positive samples in Kabale, none had
I164L mutations. Among the twelve I164L positives three were male, ages ranged
from 5 to 90 years of age. None of those with the I164L mutation had travelled in
the 8 weeks prior to the survey, although three were from households from which
at least one household member had travelled during that period. Haplotypes were
determined in non-mixed infections and showed the dhfr I164L mutation occurs in
both as a N51I + S108N + I164L haplotype (n = 2) and N51I + C59R + S108N + I164L
haplotype (n = 5). Genotyping of flanking microsatellite markers showed that the
I164L occurred independently on the triple mutant (N51I, C59R + S108N) and double
mutant (N51I + S108N) background. CONCLUSIONS: There is sustained local
transmission of parasites with the dhfr I164L mutation in Rukungiri and no
evidence to indicate its occurrence is associated with recent travel to highly
resistant neighbouring areas. The emergence of a regional cluster of I164L in SW
Uganda and Rwanda indicates that transmission of I164L is facilitated by strong
drug pressure in low transmission areas potentially catalysed in those areas by
travel and the importation of parasites from relatively higher transmission
settings.
PMID- 28415997
TI - Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF
kappaB/MAPK signaling.
AB - BACKGROUND: Dusuqing granules (DSQ) have been used in the treatment of bacterial
pneumonia clinically, with remarkable benefits. This study was initiated to
explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor
(NF)-kappaB/mitogen-activated protein kinase (MAPK) signaling in bacterial
pneumonia rats. METHODS: Rat model was duplicated with Klebsiella pneumonia by a
one-time intratracheal injection. Rats were randomized into control, model, DSQ
and levofloxacin (LVX) groups. After administrated with appropriate medicines for
7 days, lung tissues were harvested and prepared for pathological analysis, and
interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage
inflammatory protein (MIP)-2 detections. NF-kappaB mRNA was measured by real-time
qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44
were determined by Western blotting. RESULTS: Marked pathological impairments
were observed in model rats, whereas were improved in DSQ group. The cytokines
levels, NF-kappaB mRNA expression and the phosphorylation of P38MAPK, JNK46/54
and ERK42/44 proteins were significantly higher in model group, and were
significantly depressed in DSQ group. CONCLUSION: The protective effects of DSQ
on Klebsiella pneumonia might be attributed to its inactivative effects of NF
kappaB/ MAPK pathway.
PMID- 28415998
TI - Effectiveness of current policing-related mental health interventions in England
and Wales and Crisis Intervention Teams as a future potential model: a systematic
review.
AB - BACKGROUND: Experiencing mental ill health adds a layer of complexity for
individuals in touch with the justice system and for those responsible for
working in the justice service with these individuals, such as frontline police
officers. In England and Wales, there are three commonly used but not necessarily
commonly designed or operated, mental health interventions associated with
policing, Liaison and Diversion, Street Triage and specialist staff embedded in
Police Contact Control Rooms. A fourth US designed model, Crisis Intervention
Teams (CITs), is now attracting some interest in England and Wales, and these
four are to be considered in this review. A fifth intervention, Mental Health
Courts, was trialed but has now been abandoned in England and Wales and so has
been excluded, but remains in use elsewhere. In recent years, there has been an
increase in the level of investment related to these intervention options. This
has largely been without an evidence base being available to aid design,
structure, and consistency of approach. The review will address this gap and
provide a systematic review of each of these options. This will provide a
baseline of research evidence for those who commission and provide services for
individuals experiencing mental ill health and who are in contact with the
justice system. METHODS: Twenty-nine relevant databases and sources have been
selected which will be systematically searched to locate relevant studies. These
studies have to meet the set inclusion criteria which require them to report an
objective outcome measure(s) in respect of offending or mental health outcomes
and to have an experimental or quasi-experimental design including a comparator
group(s) or a pre/post comparison. The review will exclude PhD theses, papers in
non-English languages and papers published prior to 1980. Keywords have been
collected through canvassing experts' opinion, literature review, controlled
vocabulary and reviewing the results of a primary scoping review carried out to
aid the development of the PICO, composed of Population/Participants,
Intervention/Indicator, Comparator/Control, and Outcomes. For the proposed
review, the key elements of the PICO are the following: persons with mental
health problems, symptoms or diagnoses who come into contact with the police;
interventions involving partnership working between police and mental health
nurses and related professionals to divert those with mental health problems away
from criminal justice processes; comparisons with control groups or areas where
such interventions have not been introduced; and outcomes concerning criminal
justice and health outcomes. The results of the searches will be screened using
the set criteria and the selected papers reviewed and analysed to allow findings
regarding these interventions to be reported. DISCUSSION: The objectives of the
review are firstly to identify and report research on the relevant interventions,
nationally and internationally and then secondly to consider, when possible,
which interventions or aspects of those interventions are effective. This is
judged with regard to changes in mental health status or service use and future
offending behaviour. The approaches to be considered have gained a good deal of
support and funding over recent years, and this review will provide a systematic
review of the underpinning research evidence to inform future commissioning,
service design and investment decisions.
PMID- 28415999
TI - Feasibility and effectiveness of a telephone-based social support intervention
for informal caregivers of people with dementia: Study protocol of the TALKING
TIME project.
AB - BACKGROUND: Caring for people with dementia at home requires a significant amount
of time, organization, and commitment. Therefore, informal caregivers, mainly
relatives, of people with dementia often feel a high burden. Although on-site
support groups are known to have positive effects on the subjective well-being
(SWB) and perceived social support of informal caregivers, there are cases in
which relatives have either no time or no opportunity to leave the person alone
or in which there are no support groups nearby. The TALKING TIME project aims to
close this supply gap by providing structured telephone-based support groups in
Germany for the first time. International studies have shown benefits for
informal caregivers. METHODS: The TALKING TIME study is a randomized controlled
trial. The effects of the 3-month TALKING TIME intervention will be compared with
those of a control group without intervention at two time points (baseline = T0,
after 3 months = T1). The control group will receive the TALKING TIME
intervention after T1. With a planned sample size of 88 participants, the study
is powered to detect an estimated effect size of 0.70 for psychological quality
of life, considering an alpha of 0.05 (two-sided), a power of 80%. Caregivers are
informal caregivers who are eligible if they are 18 years of age or older and
have cared for a person with diagnosed dementia for at least four hours, four
days per week, in the past six months. The exclusion criteria are psychiatric
disorders of the informal caregiver. The primary outcome is the mental component
summary of the SF-12 rated by informal caregivers. The secondary outcomes for
informal caregivers are the physical component summary of the SF-12, the
Perceived Social Support Caregiver Scale (SSCS) score, and the Caregiver Reaction
Scale (CRS) score. The secondary outcome for care recipients is the
Neuropsychiatric Inventory (NPI-Q). For the process evaluation, different
quantitative and qualitative data sources will be collected to address reach,
fidelity, dosage and context. DISCUSSION: The results will provide further
information on the effectiveness and optimization of telephone-based support
groups for informal caregivers of people with dementia, which can help guide the
further development of effective telephone-based social support group
interventions. TRIAL REGISTRATION: Clinical Trials: NCT02806583 , June 9, 2016.
PMID- 28416000
TI - Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case
report.
AB - BACKGROUND: Tuberculosis remains a public health problem in developing countries
and is associated with lethal central nervous system complications. Intracranial
tuberculomas occur in 13% of children with neurotuberculosis. Patients with
trisomy 21 have an increased risk for stroke, which usually stems from
cardiovascular defects. CASE PRESENTATION: We report a case of a 12-year-old
Sudanese boy with trisomy 21 who was presented to our hospital with focal
convulsions and right-sided weakness. The results of neuroimaging and
histopathological examinations were consistent with cerebral tuberculoma. The
patient had a good initial response to antituberculosis drugs and steroids. To
the best of our knowledge, this is the first case report of multiple brain
tuberculomas described in a child with trisomy 21. CONCLUSIONS: Patients with
trisomy 21 have an increased risk for stroke. Our patient had an exceptional case
of stroke caused by tuberculoma. The present case emphasizes the need to consider
tuberculomas in the differential diagnosis of children with neurological symptoms
living in areas of high tuberculosis incidence.
PMID- 28416001
TI - Assessing environmental factors associated with regional schistosomiasis
prevalence in Anhui Province, Peoples' Republic of China using a geographical
detector method.
AB - BACKGROUND: Schistosomiasis is a water-borne disease caused by trematode worms
belonging to genus Schistosoma, which is prevalent most of the developing world.
Transmission of the disease is usually associated with multiple biological
characteristics and social factors but also factors can play a role. Few studies
have assessed the exact and interactive influence of each factor promoting
schistosomiasis transmission. METHODS: We used a series of different detectors
(i.e., specific detector, risk detector, ecological detector and interaction
detector) to evaluate separate and interactive effects of the environmental
factors on schistosomiasis prevalence. Specifically, (i) specific detector
quantifies the impact of a risk factor on an observed spatial disease pattern,
which were ranked statistically by a value of Power of Determinate (PD)
calculation; (ii) risk detector detects high risk areas of a disease on the
condition that the study area is stratified by a potential risk factor; (iii)
ecological detector explores whether a risk factor is more significant than
another in controlling the spatial pattern of a disease; (iv) interaction
detector probes whether two risk factors when taken together weaken or enhance
one another, or whether they are independent in developing a disease. Infection
data of schistosomiasis based on conventional surveys were obtained at the county
level from the health authorities in Anhui Province, China and used in
combination with information from Chinese weather stations and internationally
available environmental data. RESULTS: The specific detector identified various
factors of potential importance as follows: Proximity to Yangtze River (0.322) >
Land cover (0.285) > sunshine hours (0.256) > population density (0.109) >
altitude (0.090) > the normalized different vegetation index (NDVI) (0.077) >
land surface temperature at daytime (LSTday) (0.007). The risk detector indicated
that areas of schistosomiasis high risk were located within a buffer distance of
50 km from Yangtze River. The ecological detector disclosed that the factors
investigated have significantly different effects. The interaction detector
revealed that interaction between the factors enhanced their main effects in most
cases. CONCLUSION: Proximity to Yangtze River had the strongest effect on
schistosomiasis prevalence followed by land cover and sunshine hours, while the
remaining factors had only weak influence. Interaction between factors played an
even more important role in influencing schistosomiasis prevalence than each
factor on its own. High risk regions influenced by strong interactions need to be
targeted for disease control intervention.
PMID- 28416002
TI - Biological effects of exposure to static electric fields in humans and
vertebrates: a systematic review.
AB - BACKGROUND: High-voltage direct current (HVDC) lines are the technology of choice
for the transport of large amounts of energy over long distances. The operation
of these lines produces static electric fields (EF), but the data reviewed in
previous assessments were not sufficient to assess the need for any environmental
limit. The aim of this systematic review was to update the current state of
research and to evaluate biological effects of static EF. METHODS: Using the
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)
recommendations, we collected and evaluated experimental and epidemiological
studies examining biological effects of exposure to static EF in humans (n = 8)
and vertebrates (n = 40). RESULTS: There is good evidence that humans and animals
are able to perceive the presence of static EF at sufficiently high levels. Hair
movements caused by electrostatic forces may play a major role in this
perception. A large number of studies reported responses of animals (e.g.,
altered metabolic, immunologic or developmental parameters) to a broad range of
static EF strengths as well, but these responses are likely secondary
physiological responses to sensory stimulation. Furthermore, the quality of many
of the studies reporting physiological responses is poor, which raises concerns
about confounding. CONCLUSION: The weight of the evidence from the literature
reviewed did not indicate that static EF have adverse biological effects in
humans or animals. The evidence strongly supported the role of superficial
sensory stimulation of hair and skin as the basis for perception of the field, as
well as reported indirect behavioral and physiological responses. Physical
considerations also preclude any direct effect of static EF on internal
physiology, and reports that some physiological processes are affected in minor
ways may be explained by other factors. While this literature does not support a
level of concern about biological effects of exposure to static EF, the
conditions that affect thresholds for human detection and possible annoyance at
suprathreshold levels should be investigated.
PMID- 28416003
TI - Characterization and risk estimate of cancer in patients with primary Sjogren
syndrome.
AB - BACKGROUND: The purpose of this study is to characterize the risk of cancer in a
large cohort of patients with primary Sjogren syndrome (SjS). METHODS: We had
analyzed the development of cancer in 1300 consecutive patients fulfilling the
2002 SjS classification criteria. The baseline clinical and immunological
characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis
as predictors of cancer using Cox proportional hazards regression analysis
adjusted for age at diagnosis and gender. The sex-and age-specific standardized
incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data.
RESULTS: After a mean follow-up of 91 months, 127 (9.8%) patients developed 133
cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT
and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS
correlated with the risk of hematological neoplasia and cryoglobulins with a high
risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias
had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3
levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and
low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid
cancer was 1.13 and 11.02 for hematological cancer. SIRs for specific cancers
were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for
Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer,
4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer.
CONCLUSIONS: One third of cancers developed by patients with primary SjS are B
cell lymphomas. The prognostic factors identified at SjS diagnosis differed
according to the subtype of B-cell lymphoma developed. Primary SjS is also
associated with the development of some non-hematological cancers (thyroid, oral
cavity, and stomach).
PMID- 28416005
TI - Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers
with immune-mediated rheumatic disease.
AB - Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by
immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic
stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear
antibodies (ANA), which are also commonly present in the autoimmune disease
systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD
indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute
phase protein, is a quantitative marker of inflammation for many diseases and is
used for diagnosing and monitoring systemic inflammation in both humans and dogs.
However, in human SLE, CRP concentrations are often elevated but correlate poorly
with disease activity; they can be low in individual patients with active
disease. The aim of the study was to investigate CRP in a group of NSDTRs with
the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would
be increased in dogs with IMRD compared to healthy dogs, but that the increase
would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs
and 19 healthy control NSDTRs using two different canine-specific CRP assays.
Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but
the concentrations were below the clinical decision limit for systemic
inflammation for most of the IMRD dogs. These results indicate that CRP
concentrations were increased in dogs with IMRD and ANA, but the increase was
mild, similar to what has been observed in human SLE.
PMID- 28416004
TI - Clinical study of children with Takayasu arteritis: a retrospective study from a
single center in China.
AB - BACKGROUND: Delayed diagnosis of childhood Takayasu arteritis (TA) is common due
to its atypical symptoms. The objective of the present study was to summarize the
clinical features of childhood TA to raise awareness and improve management.
METHODS: Eleven children diagnosed with TA at our hospital were enrolled.
Clinical information, diagnosis, treatment, and outcome were then examined
retrospectively. The Pediatric Vasculitis Activity Score (PVAS) and the Indian
Takayasu Clinical Activity Score (ITAS2010) were used to assess disease activity.
RESULTS: Male-to-female ratio was 4:7. The mean age was 9.4 (1.4-14) years and
the average time to diagnosis was 40.6 days (12-90 days). All patients suffered
from hypertension and few had immunologic abnormalities. Two patients had low
levels of autoantibodies and one had elevated immunoglobulin E levels. Aberrant
(elevated) laboratory parameters included erythrocyte sedimentation rate (ESR)
(9/10 patients, 90.0%), protein excretion (8/9 patients, 88.9%), renin
angiotensin-aldosterone system (RAAS) activity (5/5 patients, 100.0%), and serum
lipid levels (3/5 patients, 60%). The common onset patterns were headache with
convulsions (27.2%) and kidney damage (27.2%). The abdominal aorta (81.8%) and
renal artery (72.7%) were the most commonly involved vessels. At presentation,
the mean PVAS and ITAS2010 scores were 12.1 (6-26)/63 and 9.7 (5-14)/57,
respectively. All patients were treated with glucocorticoids and antihypertensive
agents; two underwent renal artery stent placement. CONCLUSION: The diagnosis of
TA should be considered in patients with pediatric hypertension and high
expression of inflammatory markers or abnormal urine results. Doppler
ultrasonography of major vessels may be helpful. PVAS and ITAS2010 both help to
evaluate disease activity, and the PVAS is recommended for patients with kidney
damage. Glucocorticoid and antihypertensive agents are effective. Interventional
therapy can be an option for patients with persistent hypertension.
PMID- 28416006
TI - Leishmania major large RAB GTPase is highly immunogenic in individuals immune to
cutaneous and visceral leishmaniasis.
AB - BACKGROUND: We previously identified a Leishmania (L.) major large RAB GTPase
(LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania
species while displaying low level of homology with mammalian homologues.
Leishmania small RAB GTPases proteins have been involved in regulation of
exocytic and endocytic pathways whereas the role of large RAB GTPases proteins
has not been characterized yet. We report here the immunogenicity of both
recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major
or L. infantum. METHODS: PBMC were isolated from individuals cured of L. major
(CCLm) or from healthy individuals. The latter were subdivided into high or low
IFN-gamma responders. Healthy high IFN-gamma responders, considered as
asymptomatics, were living in an endemic area for L. major (HHRLm) or L. infantum
(HHRLi). Healthy low IFN-gamma responders (HLR) were considered as naive
controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC.
Cytokines were analysed by CBA and ELISA and phenotypes of IFN-gamma-producing
cells were analysed by flow cytometry. RESULTS: Both rLmlRAB and rLmlRABC induced
high significant levels of IFN-gamma in CCLm, HHRLm and HHRLi groups. Phenotype
analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a
significant increase in the percentage of specific IFN-gamma-producing CD4+ and
CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHRLm.
Low but significant granzyme B levels were detected in naive group. IL-10 was
detected in immune and naive individuals. CONCLUSION: We showed that rLmlRAB
protein and its divergent carboxy-terminal part induced a predominant Th1
response in individuals immune to L. major or L. infantum. Our results suggest
that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates
against cutaneous and visceral leishmaniasis.
PMID- 28416007
TI - Disseminated alveolar echinococcosis resembling metastatic malignancy: a case
report.
AB - BACKGROUND: Alveolar echinococcosis is a potentially lethal zoonosis caused by
larval forms of the tapeworm Echinococcus multilocularis. Humans are aberrant
intermediate hosts who become infected by ingestion of egg-contaminated food or
water or via physical contact with domestic or wild animals that carry the
parasite in their small intestine. In humans, the disease usually affects the
liver and can spread to other organs causing metastatic infiltration. In this
report, we describe an advanced presentation of human alveolar echinococcosis
mimicking metastatic malignancy. CASE PRESENTATION: A 62-year-old white woman was
evaluated for fever, jaundice, and abdominal pain, associated with significant
weight loss. She lived in a rural area in Switzerland and used to eat wild forest
fruits and mushrooms. She owned cats that used to hunt rodents. On physical
examination, she appeared severely ill with cachexia, altered mental status,
jaundice, and massive hepatomegaly. Laboratory tests showed cholestasis with
preserved liver function. An abdominal computed tomography scan showed an
enlarged liver with a huge cystic mass in the right lobe extending into the left
lobe, infiltrating her hepatic hilum, causing intrahepatic bile duct dilation and
occlusion of her right portal vein. A chest computed tomography scan showed
multiple calcified bilateral pulmonary nodules. Her clinical and radiological
presentation resembled an advanced neoplastic disease. Serologic tests for
Echinococcus multilocularis were positive. The diagnosis of alveolar
echinococcosis was established on her past history of exposure, imaging, and
serology results. CONCLUSIONS: Clinical presentation and radiologic imaging
findings of disseminated alveolar echinococcosis can mimic metastatic malignancy,
and diagnosis can be challenging in atypically advanced cases. As the incidence
of human alveolar echinococcosis appears to be increasing in Europe and
Switzerland, physicians should be aware of alveolar echinococcosis, its
epidemiology, and its clinical features.
PMID- 28416008
TI - A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian
perspective.
AB - Physicians often come across with cases of vitamin K antagonists-dependent
coagulopathy for reasons such as accidental use of the vitamin K antagonists
(VKA), excessive administration of prescribed anticoagulants of indirect action
or not reported administration of vitamin K antagonists due to memory impairment
and/or other mental disorders, even deliberate use thereof (attempt to murder or
suicide). Rodenticide-poisoning (coumarins, warfarins) via food or occupational
accidents are difficult to diagnose. This article discusses different types of
acquired vitamin K-dependent coagulopathy. Differential diagnosis is primarily
based on patient statements before additional causes of vitamin K deficiency are
explored. Even when pathological vitamin K deficiency is not determined,
appropriate and urgent medical treatment is necessary: administration of fresh
frozen plasma or concentrated factors of the prothrombin complex, administration
of vitamin K remedies along with symptomatic therapy. With early diagnosis and
prescription of appropriate therapy, prognosis is favorable. Reasons for vitamin
K antagonists-dependent coagulopathy cases.
PMID- 28416009
TI - Use of Lot quality assurance sampling surveys to evaluate community health worker
performance in rural Zambia: a case of Luangwa district.
AB - BACKGROUND: The Better Health Outcomes through Mentoring and Assessment (BHOMA)
project is a cluster randomized controlled trial aimed at reducing age
standardized mortality rates in three rural districts through involvement of
Community Health Workers (CHWs), Traditional Birth Attendants (TBAs), and
Neighborhood Health Committees (NHCs). CHWs conduct quarterly surveys on all
households using a questionnaire that captures key health events occurring within
their catchment population. In order to validate contact with households, we
utilize the Lot Quality Assurance Sampling (LQAS) methodology. In this study, we
report experiences of applying the LQAS approach to monitor performance of CHWs
in Luangwa District. METHODS: Between April 2011 and December 2013, seven health
facilities in Luangwa district were enrolled into the BHOMA project. The health
facility catchment areas were divided into 33 geographic zones. Quality assurance
was performed each quarter by randomly selecting zones representing about 90% of
enrolled catchment areas from which 19 households per zone where also randomly
identified. The surveys were conducted by CHW supervisors who had been trained on
using the LQAS questionnaire. Information collected included household identity
number (ID), whether the CHW visited the household, duration of the most recent
visit, and what health information was discussed during the CHW visit. The
threshold for success was set at 75% household outreach by CHWs in each zone.
RESULTS: There are 4,616 total households in the 33 zones. This yielded a target
of 32,212 household visits by community health workers during the 7 survey
rounds. Based on the set cutoff point for passing the surveys (at least 75%
households confirmed as visited), only one team of CHWs at Luangwa high school
failed to reach the target during round 1 of the surveys; all the teams otherwise
registered successful visits in all the surveys. CONCLUSIONS: We have employed
the LQAS methodology for assurance that quarterly surveys were successfully done.
This methodology proved helpful in identifying poorly performing CHWs and could
be useful for evaluating CHW performance in other areas. TRIAL REGISTRATION:
Identifier: NCT01942278 . Date of Registration: September 2013.
PMID- 28416010
TI - The effect of thymoquinone coating on adhesive properties of polypropylene mesh.
AB - BACKGROUND: An incisional hernia is a common complication following abdominal
surgery. Polypropylene mesh is frequently used in the repair of such defects and
has nearly become the standard surgical treatment modality. Though they are very
effective in reducing recurrence, mesh materials exhibit a strong stimulating
effect for intraabdominal adhesion. The thymoquinone (TQ) extracted from Nigella
sativa seeds has potential medical properties. TQ has anti-inflammatory,
antioxidant and antibacterial properties. The aim of this study is to coat
polypropylene mesh with TQ in order to investigate the effect of surface
modification on intraabdominal adhesions. METHODS: TQ-coated polypropylene mesh
material was tested for cytotoxicity, contact angle, surface spectroscopy, TQ
content, sterility, and electron microscopic surface properties. An experimental
incisional hernia model was created in study groups, each consisting of 12 female
Wistar rats. The defect was closed with uncoated mesh in control group, with
polylactic acid (PLA) coated mesh and PLA-TQ coated mesh in study groups.
Adhesion scores and histopathologic properties were evaluated after sacrifice on
postoperative 21th day. RESULTS: Granuloma formation, lymphocyte and
polymorphonuclear leukocyte infiltration, histiocyte fibroblast and giant cell
formation, capillary infiltration, collagen content were significantly reduced in
the PLA-TQ coated mesh group (p < 0.05). Though not statistically significant,
likely due to the limited number of study animals, adhesion formation was also
reduced in the PLA-TQ coated mesh group (p: 0.067). CONCLUSION: TQ coated mesh is
shown to reduce adhesion formation and TQ is a promising coating material for
mesh surface modification.
PMID- 28416011
TI - Which learning activities enhance physiotherapy practice? A systematic review
protocol of quantitative and qualitative studies.
AB - BACKGROUND: Learning activities are fundamental for the development of expertise
in physiotherapy practice. Continuing professional development (CPD) encompasses
formal and informal learning activities undertaken by physiotherapists.
Identifying the most efficient and effective learning activities is essential to
enable the profession to assimilate research findings and improve clinical skills
to ensure the most efficacious care for clients. To date, systematic reviews on
the effectiveness of CPD provide limited guidance on the most efficacious models
of professional development for physiotherapists. The aim of this systematic
review is to evaluate which learning activities enhance physiotherapy practice.
METHODS: A search of Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied
Health Literature (CINAHL), PsycINFO (Psychological Abstracts), PEDro, Cochrane
Library, AMED and Educational Resources and Information Center (ERIC) will be
completed. Citation searching and reference list searching will be undertaken to
locate additional studies. Quantitative and qualitative studies will be included
if they examine the impact of learning activities on clinician's behaviour,
attitude, knowledge, beliefs, skills, self-efficacy, work satisfaction and
patient outcomes. Risk of bias will be assessed by two independent researchers.
Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and
Confidence in the Evidence from Reviews of Qualitative research (CERQual) will be
used to synthesise results where a meta-analysis is possible. Where a meta
analysis is not possible, a narrative synthesis will be conducted. SYSTEMATIC
REVIEW REGISTRATION: PROSPERO CRD42016050157.
PMID- 28416012
TI - Congenital Cytomegalovirus infection: advances and challenges in diagnosis,
prevention and treatment.
AB - Cytomegalovirus (CMV) is the most frequent cause of congenital infection
worldwide, with an estimated incidence in developing countries of 0.6-0.7% of all
live births. The burden of disease related to congenital CMV in substantial, as
it is the leading non-genetic cause of sensorineural hearing loss and an
important cause of neurodevelopmental disabilities in children. Despite its
clinical significance, congenital CMV infection often goes undetected because the
majority of infected infants are asymptomatic at birth and screening programs
have not been substantially implemented. Other than behavioral measures,
effective interventions aimed at the prevention of maternal infection and of
mother-to-child transmission are lacking. Due to a convergence of recent advances
in both diagnostic and therapeutic strategies in infants with congenital CMV,
though, the field likely will be changing rapidly over just the next few years.
Specifically, a highly-sensitive screening test with high throughput potential
has been developed, and treatment of infants symptomatically infected with
congenital CMV has proven to be well-tolerated and effective in improving long
term hearing and neurodevelopmental outcomes.This review highlights the clinical
importance of congenital CMV infection, the developments in laboratory
diagnostics, and the benefits of antiviral therapy. It also identifies the global
efforts still required in the prevention of maternal infection and in the
optimization of antiviral therapy to further reduce the burden of congenital CMV
disease.
PMID- 28416013
TI - No seasonal variation in physical activity of Han Chinese living in Beijing.
AB - BACKGROUND: Physical activity (PA) is widely acknowledged to be beneficial to
health and wellbeing, and is potentially influenced by a variety of environmental
factors such as ambient temperature, weather conditions and air pollution levels.
Since these factors vary seasonally, physical activity participation may also
respond seasonally. Current population studies to profile physical activity often
sample individuals only once, and this may result in biased estimates if there is
strong seasonal variation. METHODS: We conducted a study of 40 Han Chinese adults
living in Beijing using GT3X accelerometers. We measured PA levels every two
months across a complete year, while simultaneously monitoring ambient
temperatures and air pollution levels. Average hourly vector magnitude (VM) and
percentage time spent at each PA intensity (sedentary to light, moderate,
vigorous and very vigorous) were measured. General Linear models (GLMs) were used
to explore the effects of time of day, temperature and PM 2.5 levels on PA. One
way ANOVA was used to test whether there were seasonal differences in body weight
and body fatness. RESULTS: The main factors influencing activity levels were the
time of day and individual characteristics including age and body fatness, but
there was no significant difference between the months. In addition, there was no
significant impact of either ambient temperature or air pollution levels (PM2.5).
There were also no significant differences over the year in the time spent at
sedentary-light, moderate and very vigorous PA levels, but for vigorous PA level
which occupied less than 0.5% daily physical activity, both month and individual
were significant factors. CONCLUSIONS: The relatively constant pattern of urban
daily life, independent of time of year, may override the potential impacts of
environmental factors that would be anticipated to impact PA levels. These
subjects did not specifically avoid activity coincident with elevated air
pollution levels (PM2.5). Single week long measurements of physical activity
could provide a representative measurement of the physical active levels in this
population.
PMID- 28416015
TI - Costs and health-related quality of life in Alpha-1-Antitrypsin Deficient COPD
patients.
AB - BACKGROUND: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored
genetic disease. METHODS: Direct and indirect costs (based on self-reported
information on healthcare utilization) and health-related quality of life (HRQL,
as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients
(106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without
AATD participating in the COSYCONET COPD cohort. The medication costs of AT were
excluded from all analyses to reveal differences associated with morbidity
profiles. The association of AATD (with/without AT) with costs or HRQL was
examined using generalized linear regression modelling (GLM) adjusting for age,
sex, GOLD grade, BMI, smoking status, education and comorbidities. RESULTS:
Adjusted mean direct annual costs were ?6,099 in AATD patients without AT, ?7,117
in AATD patients with AT (excluding costs for AT), and ?7,460 in COPD patients
without AATD. AATD with AT was significantly associated with higher outpatient
(+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT)
compared with COPD patients without AATD. There were no significant differences
between groups regarding indirect costs and HRQL. CONCLUSION: Apart from AT
costs, AATD patients tended to have lower, though not significant, overall costs
and similar HRQL compared to COPD patients without AATD. AT was not associated
with lower costs or higher HRQL. TRIAL REGISTRATION: NCT01245933.
PMID- 28416016
TI - Variation in rates of ICU readmissions and post-ICU in-hospital mortality and
their association with ICU discharge practices.
AB - BACKGROUND: Variation in intensive care unit (ICU) readmissions and in-hospital
mortality after ICU discharge may indicate potential for improvement and could be
explained by ICU discharge practices. Our objective was threefold: (1) describe
variation in rates of ICU readmissions within 48 h and post-ICU in-hospital
mortality, (2) describe ICU discharge practices in Dutch hospitals, and (3) study
the association between rates of ICU readmissions within 48 h and post-ICU in
hospital mortality and ICU discharge practices. METHODS: We analysed data on
42,040 admissions to 82 (91.1%) Dutch ICUs in 2011 from the Dutch National
Intensive Care Evaluation (NICE) registry to describe variation in standardized
ICU readmission and post-ICU mortality rates using funnel-plots. We send a
questionnaire to all Dutch ICUs. 75 ICUs responded and their questionnaire data
could be linked to 38,498 admissions in the NICE registry. Generalized estimation
equations analyses were used to study the association between ICU readmissions
and post-ICU mortality rates and the identified discharge practices, i.e. (1) ICU
discharge criteria; (2) bed managers; (3) early discharge planning; (4) step-down
facilities; (5) medication reconciliation; (6) verbal and written handover; (7)
monitoring of post-ICU patients; and (8) consulting ICU nurses. In all analyses,
the outcomes were corrected for patient-related confounding factors. RESULTS: The
standardized rate of ICU readmissions varied between 0.14 and 2.67 and 20.8% of
the hospitals fell outside the 95% control limits and 3.6% outside the 99.8%
control limits. The standardized rate of post-ICU mortality varied between 0.07
and 2.07 and 17.1% of the hospitals fell outside the 95% control limits and 4.9%
outside the 99.8% control limits. We could not demonstrate an association between
the eight ICU discharge practices and rates of ICU readmissions or post-ICU in
hospital mortality. Implementing a higher number of ICU discharge practices was
also not associated with better patient outcomes. CONCLUSIONS: We found both
variation in patient outcomes and variation in ICU discharge practices between
ICUs. However, we found no association between discharge practices and rates of
ICU readmissions or post-ICU mortality. Further research is necessary to find
factors, which may influence these patient outcomes, in order to improve quality
of care.
PMID- 28416017
TI - Patient complexity and genotype-phenotype correlations in biliary atresia: a
cross-sectional analysis.
AB - BACKGROUND: Biliary Atresia (BA) is rare and genetically complex, and the
pathogenesis is elusive. The disease course is variable and can represent
heterogeneity, which hinders effective disease management. Deciphering the BA
phenotypic variance is a priority in clinics and can be achieved by the
integrative analysis of genotype and phenotype. We aim to explore the BA
phenotypic features and to delineate the source of its variance. METHODS: The
study is a cross-sectional observational study collating with case/control
association analysis. One-hundred-and-eighty-one type III non-syndromic BA
patients and 431 controls were included for case-control association tests,
including 89 patients (47.19% males, born June 15th, 1981 to September 17th,
2007) have detailed clinical records with follow-up of the disease course (median
~17.2 years). BA-association genes from the genome-wide gene-based association
test on common genetic variants (CV) and rare copy-number-variants (CNVs) from
the genome-wide survey, the later comprise only CNVs > 100 kb and found in the BA
patients but not in the local population (N = 1,381) or the database (N =
11,943). Hereby comorbidity is defined as a chronic disease that affects the BA
patients but has no known relationship with BA or with the BA treatment. We
examined genotype-phenotype correlations of CNVs, connectivity of these novel
variants with BA-associated CVs, and their role in the BA candidate gene network.
RESULTS: Of the 89 patients, 41.57% have comorbidities, including autoimmune
allergic disorders (22.47%). They carried 29 BA-private CNVs, including 3 CNVs
underpinning the carriers' immunity comorbidity and one JAG1 micro-deletion. The
BA-CNV-intersected genes (N = 102) and the CV-tagged genes (N = 103) were both
enriched with immune-inflammatory pathway genes (FDR q < 0.20), and the two gene
sets were interconnected (permutation p = 0.039). The molecular network
representing CVs and rare-CNV association genes fit into a core/periphery
structure, the immune genes and their related modules are found at the coherence
core of all connections, suggesting its dominant role in the BA pathogenesis
pathway. CONCLUSIONS: The study highlights a patient-complexity phenomenon as a
novel BA phenotypic feature, which is underpinned by rare-CNVs that biologically
converge with CVs into the immune-inflammatory pathway and drives the BA
occurrence and the likely BA association with immune diseases in clinics.
PMID- 28416018
TI - Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from
children with diffuse midline glioma.
AB - Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are
highly morbid glial neoplasms of the thalamus or brainstem that typically arise
in young children and are not surgically resectable. These tumors are
characterized by a high rate of histone H3 mutation, resulting in replacement of
lysine 27 with methionine (K27M) in genes encoding H3 variants H3.3 (H3F3A) and
H3.1 (HIST1H3B). Detection of these gain-of-function mutations has clinical
utility, as they are associated with distinct tumor biology and clinical
outcomes. Given the paucity of tumor tissue available for molecular analysis and
relative morbidity of midline tumor biopsy, CSF-derived tumor DNA from patients
with diffuse midline glioma may serve as a viable alternative for clinical
detection of histone H3 mutation. We demonstrate the feasibility of two
strategies to detect H3 mutations in CSF-derived tumor DNA from children with
brain tumors (n = 11) via either targeted Sanger sequencing of H3F3A and
HIST1H3B, or H3F3A c.83 A > T detection via nested PCR with mutation-specific
primers. Of the six CSF specimens from children with diffuse midline glioma in
our cohort, tumor DNA sufficient in quantity and quality for analysis was
isolated from five (83%), with H3.3K27M detected in four (66.7%). In addition,
H3.3G34V was identified in tumor DNA from a patient with supratentorial
glioblastoma. Test sensitivity (87.5%) and specificity (100%) was validated via
immunohistochemical staining and Sanger sequencing in available matched tumor
tissue specimens (n = 8). Our results indicate that histone H3 gene mutation is
detectable in CSF-derived tumor DNA from children with brain tumors, including
diffuse midline glioma, and suggest the feasibility of "liquid biopsy" in lieu
of, or to complement, tissue diagnosis, which may prove valuable for
stratification to targeted therapies and monitoring treatment response.
PMID- 28416020
TI - Patient- and family-centered performance measures focused on actionable processes
of care for persistent and chronic critical illness: protocol for a systematic
review.
AB - BACKGROUND: Approximately 5 to 10% of critically ill patients transition from
acute critical illness to a state of persistent and in some cases chronic
critical illness. These patients have unique and complex needs that require a
change in the clinical management plan and overall goals of care to a focus on
rehabilitation, symptom relief, discharge planning, and in some cases, end-of
life care. However, existing indicators and measures of care quality, and tools
such as checklists, that foster implementation of best practices, may not be
sufficiently inclusive in terms of actionable processes of care relevant to these
patients. Therefore, the aim of this systematic review is to identify the
processes of care, performance measures, quality indicators, and outcomes
including reports of patient/family experience described in the current evidence
base relevant to patients with persistent or chronic critical illness and their
family members. METHODS: Two authors will independently search from inception to
November 2016: MEDLINE, Embase, CINAHL, Web of Science, the Cochrane Library,
PROSPERO, the Joanna Briggs Institute and the International Clinical Trials
Registry Platform. We will include all study designs except case series/reports
of <10 patients describing their study population (aged 18 years and older) using
terms such as persistent critical illness, chronic critical illness, and
prolonged mechanical ventilation. Two authors will independently perform data
extraction and complete risk of bias assessment. Our primary outcome is to
determine actionable processes of care and interventions deemed relevant to
patients experiencing persistent or chronic critical illness and their family
members. Secondary outcomes include (1) performance measures and quality
indicators considered relevant to our population of interest and (2) themes
related to patient and family experience. DISCUSSION: We will use our systematic
review findings, with data from patient, family member and clinician interviews,
and a subsequent consensus building process to inform the development of quality
metrics and tools to measure processes of care, outcomes and experience for
patients experiencing persistent or chronic critical illness and their family
members. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016052715.
PMID- 28416021
TI - Effects of GABAB receptors in the insula on recognition memory observed with
intellicage.
AB - BACKGROUND: Insular function has gradually become a topic of intense study in
cognitive research. Recognition memory is a commonly studied type of memory in
memory research. GABABR has been shown to be closely related to memory formation.
In the present study, we used intellicage, which is a new intelligent behavioural
test system, and a bilateral drug microinjection technique to inject into the
bilateral insula, to examine the relationship between GABABR and recognition
memory. METHODS: Male Sprague-Dawley rats were randomly divided into control,
Sham, Nacl, baclofen and CGP35348 groups. Different testing procedures were
employed using intellicage to detect changes in rat recognition memory. The
expression of GABABR (GB1, GB2) in the insula of rats was determined by
immunofluorescence and western blotting at the protein level. In addition, the
expression of GABABR (GB1, GB2) was detected by RT-PCR at the mRNA level.
RESULTS: The results of the intellicage test showed that recognition memory was
impaired in terms of position learning, punitive learning and punitive reversal
learning by using baclofen and CGP35348. In position reversal learning, no
significant differences were found in terms of cognitive memory ability between
the control groups and the CGP and baclofen groups. Immunofluorescence data
showed GABABR (GB1, GB2) expression in the insula, while data from RT-PCR and
western blot analysis demonstrated that the relative expression of GB1 and GB2
was significantly increased in the baclofen group compared with the control
groups. In the CGP35348 group, the expression of GB1 and GB2 was significantly
decreased, but there was no significant difference in GB1 or GB2 expression in
the control groups. CONCLUSIONS: GABABR expression in the insula plays an
important role in the formation of recognition memory in rats.
PMID- 28416019
TI - A window into living with an undiagnosed disease: illness narratives from the
Undiagnosed Diseases Network.
AB - BACKGROUND: Patients' stories of their illnesses help bridge the divide between
patients and providers, facilitating more humane medical care. Illness narratives
have been classified into three types: restitution (expectation of recovery),
chaos (suffering and loss), and quest (unexpected positive effect from illness).
Undiagnosed patients have unique illness experiences and obtaining their
narratives would provide insights into the medical and emotional impact of living
with an undiagnosed illness. Adults and children with undiagnosed diseases apply
to be evaluated by the Undiagnosed Diseases Network (UDN). Written illness
narratives from 40 UDN applicants, including 20 adult probands who applied for
themselves and 20 parents who applied for their children, were analyzed for: 1)
narrative content and 2) narrative type. RESULTS: Narrative content: could be
grouped into three themes: 1) Expectations of the UDN: the majority felt they had
no further healthcare options and hoped the UDN would provide them with a
diagnosis, with the adults expecting to return to their previously healthy life
and the parents wanting information to manage their child's healthcare. 2)
Personal medical information: the narratives reported worsening of symptoms and
some offered opinions regarding the cause of their illness. The proband
narratives had few objective findings, while parental narratives had detailed
objective information. 3) Experiences related to living with their undiagnosed
illness: frustration at being undiagnosed was expressed. The adults felt they had
to provide validation of their symptoms to providers, given the lack of objective
findings. The parents worried that something relevant to their child's management
was being overlooked. Narrative type: All the narratives were of the chaos type,
but for different reasons, with the probands describing loss and suffering and
the parents expressing fear for their child's future. The parental narratives
also had elements of restitution and quest, with acceptance of "a new normal",
and an emphasis on the positive aspects of their child's illness which was absent
from the probands. CONCLUSIONS: These narratives illustrate the chaos that
coexists with being undiagnosed. The differences between the proband and parental
narratives suggest that these two groups have different needs that need to be
considered during their evaluation and management.
PMID- 28416022
TI - Specific or general exercise strategy for subacromial impingement syndrome-does
it matter? A systematic literature review and meta analysis.
AB - BACKGROUND: Exercise is frequently suggested as a treatment option for patients
presenting with symptoms of subacromial impingement syndrome. Some would argue
implementing a specific exercise strategy with special focus on correction of
kinematic deficits would be superior to general exercise strategy. There is
however a lack of evidence comparing such exercise strategies to determine which
is the most effective in the treatment of subacromial impingement syndrome. The
aim of this review is to evaluate whether implementing specific exercise
strategies involving resistive exercises are more effective than a general
exercise strategy for the treatment of patients with subacromial impingement
syndrome. METHODS: Randomized controlled trials were identified through an
electronic search on PubMed/MEDLINE, EMBASE, Cochrane Central Register of
Controlled Trials, Web of Science and PEDro. In addition, article reference lists
and Clinicaltrials.gov were searched. Studies were considered eligible if they
included interventions with resistive specific exercises as compared to general
resistance exercise. Four reviewers assessed risk of bias and methodological
quality guided by Cochrane recommendations. Results were synthesised
qualitatively or quantitatively, where appropriate. RESULTS: Six randomized
controlled trials were included with 231 participants who experienced symptoms of
subacromial impingement syndrome. Four studies evaluated the effectiveness of
specific scapular exercise strategy and two studies evaluated the effectiveness
of specific proprioceptive strategy. Five studies were of moderate quality and
one study was of low quality. No consistent statistical significant differences
in outcomes between treatment groups were reported in the studies. Standardized
mean difference (SMD) for pain was SMD -0.19 (95% CI -0.61, 0.22) and SMD 0.30
(95% CI -0.16, 0.76) for function. CONCLUSIONS: There is insufficient evidence to
support or refute the effectiveness of specific resistive exercise strategies in
the rehabilitation of subacromial impingement syndrome. More high quality
research is needed to accurately assess this. This review provides suggestions on
how to improve the methodological design of future studies in this area.
PMID- 28416024
TI - Polymorphism in male genitalia of Aedes (Ochlerotatus) scapularis Rondani, 1848.
AB - Morphology of male genitalia of culicids is generally species-specific and often
used as a taxonomic marker. However, some characters of the male genitalia vary
intraspecifically and are not taxonomically diagnostic. This might be the case of
Aedes scapularis, a Neotropical culicid with vector competence for arboviruses
and filarial worms. Males of this species may or not present a retrorse process
(RP) in the genitalic claspette filaments, which led authors to suspect that this
variance might be indicative of population divergence or incipient speciation
process. This suspicion has not been investigated hitherto and it is not known if
there are variable patterns of RPs. We hypothesized that the presence of the RP
varies intraspecifically in Ae. scapularis and then we statistically evaluated
the variability of this character in a single population. To this study the
genitalia of 73 males of Ae. scapularis were prepared, and their RPs were
meristically quantified and categorized according to the phenotypes observed. We
noted that the presence or RPs is a polymorphic character because it varied inter
and intra-individually. The presence of a single RP on each claspette filament
was the predominant pattern (77%), but absent or multiple RPs in each filament
were also found either in bilateral symmetry or asymmetry. Thus, we conclude that
the presence of RPs owing to its high variability is not indicative of
populational divergence or diagnostic of species complex within Ae. scapularis.
PMID- 28416025
TI - Healthcare innovation and patent law's 'pharmaceutical privilege': is there a
pharmaceutical privilege? And if so, should we remove it?
AB - This article reviews current trends in patent claims regarding personalised,
stratified and precision medicine. These trends are not particularly well
understood by policymakers, even less by the public, and are quite recent.
Consequently, their implications for the public interest have hardly been thought
out. Some see personalised and other secondary drug patent claims as promoting
better targeted treatment. Others are inclined to see them as ?manifestations of
'evergreening' whereby companies are, in some cases quite cynically, trying to
extend market monopolies in old products or creating new monopolies based on
supposedly improved versions of such earlier drugs. The article claims that the
relaxation of 'novelty' is a privilege unavailable to inventions in other fields
and that on balance the patent system does privilege this industry and that no
adequate case has yet been made thus far to prove the public benefits overall.
PMID- 28416023
TI - The new Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry:
design, rationale, and characteristics of patients enrolled in the first 12
months.
AB - BACKGROUND: Herein we describe the history, design, and rationale of the new
Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and
present the characteristics of patients with juvenile idiopathic arthritis (JIA)
enrolled in the first 12 months of operation. METHODS: The CARRA Registry began
prospectively collecting data in the United States and Canada in July 2015 to
evaluate the safety of therapeutic agents in persons with childhood-onset
rheumatic disease, initially restricted to JIA. Secondary objectives include the
evaluation of disease outcomes and their associations with medication use and
other factors. Data are collected every 6 months and include clinical
assessments, detailed medication use, patient-reported outcomes, and safety
events. Follow-up is planned for at least 10 years for each participant and is
facilitated by a telephone call center. RESULTS: As of July 2016, 1192 patients
with JIA were enrolled in the CARRA Registry at 49 clinical sites. At enrollment,
their median age was 12.4 years old and median disease duration was 2.6 years.
Owing to preferential enrollment, patients with systemic JIA (13%) and with a
polyarticular course (75%) were over-represented compared to patients in typical
clinical practice. Approximately 49% were currently using biologic agents and
ever use of oral glucocorticoids was common (47%). The CARRA Registry provides
safety surveillance data to pharmaceutical companies to satisfy their regulatory
requirements, and several independently-funded sub-studies that use the Registry
infrastructure are underway. CONCLUSION: The new CARRA Registry successfully
enrolled nearly 1200 participants with JIA in the first 12 months of its
operation. Sustainable funding has been secured from multiple sources. The CARRA
Registry may serve as a model for the study of other uncommon diseases.
PMID- 28416026
TI - Evaluation of a pilot service to facilitate discharge of patients with stable
long-term mental health needs from secondary to primary care: the role of Primary
Care Mental Health Specialists.
AB - : Aim We aimed to evaluate a pilot service to facilitate discharge of patients
with stable long-term mental health needs from secondary to primary care.
BACKGROUND: Patients with stable long-term mental health conditions are often not
discharged from secondary mental health services when no longer needed due to
insufficient systems and processes to enable safe, effective, recovery-focussed
treatment and support. The Primary Care Mental Health Specialist (PCMHS) Service
was developed to address this gap; new PCMHS posts were introduced to act as a
conduit for patients being discharged from secondary care and a single point of
referral back into secondary care, should it be required. The two-year pilot,
across six Clinical Commissioning Groups in South East England, began in March
2013. METHODS: Interviews were conducted with all PCMHS employed in the pilot
service (n=13) and a sample of service users (n=12). The views of professionals
working alongside the service, including GPs, Psychiatrists and Mental Health
Nurses, were captured using a brief online questionnaire (n=50). Time and
Activity Recording Sheets were used to capture data required for economic
analysis. Findings Our findings indicate that the service is working well from
the perspective of patients; staff employed within the service and professionals
working alongside the service. Patients described the service as a 'safety net'
they could fall back on in case of difficulties, whereas staff used the analogy
of a 'bridge' to describe the way the service improved communication and
collaboration between the various professionals and organisations involved in the
patient's care. Improvements in well-being were seen to result from increased
support for those transitioning from secondary to primary care, a more pro-active
approach to relapse prevention and increased engagement in daily activities. Each
PCMHS covered 36 patients in a one-month period, with a unit cost of L73.01 per
patient.
PMID- 28416027
TI - Pharmacological and non-pharmacological treatment preferences of healthcare
professionals and proxies for challenging behaviors in patients with dementia.
AB - BACKGROUND: Prescribing antipsychotics to patients with neuropsychiatric symptoms
is a matter of concern. Physicians have to make treatment decisions for patients
with dementia together with proxies and/or nurses. However, it is unknown whether
physicians, nurses, and proxies' treatment preferences are aligned; hence this
study. METHODS: Sixteen treatment attributes were selected to elicit the
preferences of physicians and nurses. Ten of these attributes were used for the
proxies. Preferences were estimated using a case-1 Best-Worst-Scaling design;
respondents are asked to select the best and worst attribute on being presented
with a hypothetical patient with dementia demonstrating neuropsychiatric
symptoms. The treatments offered are: antipsychotic treatment or non
pharmaceutical regimens. RESULTS: The questionnaire was filled in by 41
physicians, 81 nurses, and 59 proxies. The non-pharmacological treatment option
was chosen by 52% of the proxies and 71% of the physicians and nurses. The
respondents who chose antipsychotics rated the aspects "fastest result" and "most
effective" as important. Physicians ranked "experience with antipsychotics" as an
important aspect for prescribing antipsychotics. Only the proxies rated the
aspect "having a low negative effect on the patient" as important. The nurses and
elderly care physicians who chose the non-pharmaceutical treatment ranked
"appropriateness" and "of little burden to the patient" as important aspects.
CONCLUSIONS: While doctors and nurses prefer non-pharmacological interventions,
proxies indicated a preference for pharmacological treatment because of the
immediate effect. However, physicians follow treatment guidelines and nurses and
proxies rely on the physician's recommendations. We suggest physicians should be
sensitive to these differences.
PMID- 28416028
TI - Attitudes and perceptions of pregnant women with CHD: results of a single-site
survey.
AB - : Introduction CHD occurs in about 1% of the United States population, and is now
the most common cardiac condition affecting women during pregnancy. METHODS: An
anonymous, single-site, cross-sectional, 50-question survey was performed at a
national Adult Congenital Heart Disease conference to assess the level of
knowledge, attitudes, and perceptions regarding cardiac care during pregnancy in
women with CHD. RESULTS: A total of 77 women completed the survey. Among them,
50% (n=39) had moderate and 38% (n=29) had severely complex disease; 30% (n=23)
of women were told that pregnancy was contraindicated given their underlying
cardiac condition. Almost two-thirds (n=50) report being categorised as high risk
for adverse cardiovascular events. During pregnancy, 84% (n=65) preferred their
cardiologist to have trained in adult CHD, 44% (n=34) were satisfied with adult
cardiologists, and 36% (n=28) with paediatric cardiologists. Only 48% (n=37) were
aware that a fetal echocardiogram was indicated. Only 35% (n=27) discussed modes
of delivery with their providers, and 70% (n=54) preferred their prenatal
cardiology visits at an adult hospital. Up to 85% (n=64) of them had discussed
contraception with their cardiologists, and 72% (n=56) felt they needed high-risk
maternal-fetal medicine to be involved with their care. CONCLUSIONS: Despite
seeking medical care, these pregnant women did not have a full understanding of
their condition and their cardiovascular risk during pregnancy. On the basis of
these results, further efforts are needed to improve the knowledge, attitudes,
and perceptions of women with CHD in relation to their cardiac and obstetric
management during pregnancy.
PMID- 28416029
TI - The health outcomes of human offspring conceived by assisted reproductive
technologies (ART).
AB - Concerns have been raised about the health and development of children conceived
by assisted reproductive technologies (ART) since 1978. Controversially, ART has
been linked with adverse obstetric and perinatal outcomes, an increased risk of
birth defects, cancers, and growth and development disorders. Emerging evidence
suggests that ART treatment may also predispose individuals to an increased risk
of chronic ageing related diseases such as obesity, type 2 diabetes and
cardiovascular disease. This review will summarize the available evidence on the
short-term and long-term health outcomes of ART singletons, as multiple
pregnancies after multiple embryos transfer, are associated with low birth weight
and preterm delivery, which can separately increase risk of adverse postnatal
outcomes, and impact long-term health. We will also examine the potential factors
that may contribute to these health risks, and discuss underlying mechanisms,
including epigenetic changes that may occur during the preimplantation period and
reprogram development in utero, and adult health, later in life. Lastly, this
review will consider the future directions with the view to optimize the long
term health of ART children.
PMID- 28416030
TI - Prevalence, neurobiology, and treatments for apathy in prodromal dementia.
AB - BACKGROUND: Apathy, characterized by diminished motivation, is a highly prevalent
neuropsychiatric symptom in dementia. However, there is a substantial knowledge
gap with regard to prevalence rates, neurobiological underpinnings, and effective
treatments for apathy in pre-dementia states, including mild cognitive impairment
(MCI) and mild behavioral impairment (MBI). METHODS: We conducted a comprehensive
literature search using MEDLINE, Embase, and PsycINFO databases to identify
available research on apathy in prodromal dementia. RESULTS: Apathy has
consistently been detected in individuals with MCI with varying prevalence rates,
and only recently has literature discussed the prevalence of apathy in MBI. Few
pharmacological treatments have been utilized for apathy, with galantamine and
risperidone showing mild reductions in apathetic behaviors. Non-pharmacological
interventions in prodromal dementia are beginning to be explored and show
promise, but few studies have replicated those results. DISCUSSION: More
comprehensive guidelines for diagnosing apathy and further research investigating
neurobiological mechanisms of apathy in MCI and MBI are required in order to
effectively treat apathetic patients in prodromal dementia.
PMID- 28416031
TI - Behavioral and psychological symptoms of dementia: prevalence, symptom groups and
their correlates in community-based older adults with dementia in Singapore.
AB - BACKGROUND: This study assessed the prevalence and factor structure of behavioral
and psychological symptoms of dementia (BPSD) in a community-based sample of
older adults with dementia and identified their correlates. METHODS: Data
collected from 399 Singapore residents with dementia aged 60 years and above,
interviewed along with a family/friend during a national survey, were used for
this analysis. Neuropsychiatric Inventory Questionnaire assessed older adults'
BPSD. Other data included socio-demographics, dementia severity, cognition,
chronic physical conditions, disability, and caregivers' burden. Exploratory
factor analysis assessed BPSD sub-groups, factor scores of which were used to
identify socio-demographic, and clinical correlates. RESULTS: Prevalence of BPSD
was 67.9% and 30% of the population had experienced three or more BPSD in the
past month. Two distinct and moderately correlated symptom groups representing
"psychosis and behavior dysregulation" and "mood disturbance and restlessness"
were identified. As factor scores for both the groups increased with older age,
poor cognition and caregiver burden, the former was also related to being never
married and having no formal education. CONCLUSIONS: Study provides evidence of
two distinct groups of BPSD and their important correlates. Clinicians treating
BPSD should consider their age and cognitive impairment and be cognizant of their
caregivers' burden.
PMID- 28416032
TI - Physiological, metabolic and transcriptional postnatal phenotypes of in vitro
fertilization (IVF) in the mouse.
AB - Approximately 1-4% of children today are conceived using assisted reproductive
technologies (ARTs), including in vitro fertilization (IVF). IVF is considered
safe and the great majority of these children are healthy, yet there is
increasing physiological and molecular evidence from animal models that ART is
associated with postnatal metabolic and cardiovascular alterations. Understanding
the mechanisms underlying these changes and determining whether they have
biological significance is of paramount importance for optimizing the design of
culture conditions and improving the health of ART children across the life
course. In this review, we examine the evidence of molecular changes present in
adult tissues of rodent offspring generated by preimplantation manipulation of
gametes and embryos. Although embryo manipulation in vitro can induce common
transcriptional effects in the blastocyst, transcriptional and metabolomic
signatures in adult IVF tissues are largely tissue-specific. However, there is
pervasive evidence of oxidative stress and metabolic dysfunction, indicating a
lasting effect of IVF on molecular physiology.
PMID- 28416033
TI - Pharmacological treatment of mixed states.
AB - Mixed states in bipolar disorder have been neglected, and the data concerning
treatment of these conditions have been relatively obscure. To address this, we
systematically reviewed published pharmacological treatment data for "mixed
states/episodes" in mood disorders, including "with mixed features" in DSM-5. We
searched PubMed, MEDLINE, The Cochrane Library, clinicaltrials.gov, and
controlled-trials.com (with different combinations of the following keywords:
"mixed states/features," "bipolar," "depressive symptoms/bipolar depression,"
"manic symptoms," "treatment," "DSM-5") through to October 2016. We applied a
quality-of-evidence approach: first-degree evidence=randomized placebo-controlled
studies of pharmacological interventions used as monotherapy; second-degree
evidence=a similar design in the absence of a placebo or of a combination therapy
as a comparative group; third-degree evidence=case reports, case series, and
reviews of published studies. We found very few primary double-blind, placebo
controlled studies on the treatment of mixed states: the preponderance of
available data derives from subgroup analysis performed on studies that
originally involved manic patients. Future research should study the effects of
treatments in mixed states defined using current criteria.
PMID- 28416034
TI - COHABITATION AND UNION DISSOLUTION IN CENTRAL UGANDA: DIFFERENCES BETWEEN
COHABITORS AND NON-COHABITORS.
AB - The aim of this paper was to establish whether the differences in the risks of
union dissolution between cohabitors and non-cohabitors in Uganda have converged
over time using event history data. Data were collected in 2013 from 1200 women
in central Uganda using retrospective methods. Of these, 839 provided information
on three types of first union: women who married directly (without first
cohabiting), those who married following cohabitation and those who were still
cohabiting. The data were analysed using decrement lifetable analysis. Though the
analysis indicated a small difference in the timing of first union dissolution
for women who married directly, no evidence was found that the difference in the
risk of union dissolution between cohabitors and non-cohabitors had converged
over the 9-year period following first union. Women's union/marriage status,
number of living children in a union, parental union status and birth cohort were
found to significantly influence the timing of union dissolution. Overall, the
rate of union dissolution was fairly high, regardless of type of union.
PMID- 28416035
TI - Measuring the Autocorrelation Function of Nanoscale Three-Dimensional Density
Distribution in Individual Cells Using Scanning Transmission Electron Microscopy,
Atomic Force Microscopy, and a New Deconvolution Algorithm.
AB - Essentially all biological processes are highly dependent on the nanoscale
architecture of the cellular components where these processes take place.
Statistical measures, such as the autocorrelation function (ACF) of the three
dimensional (3D) mass-density distribution, are widely used to characterize
cellular nanostructure. However, conventional methods of reconstruction of the
deterministic 3D mass-density distribution, from which these statistical measures
can be calculated, have been inadequate for thick biological structures, such as
whole cells, due to the conflict between the need for nanoscale resolution and
its inverse relationship with thickness after conventional tomographic
reconstruction. To tackle the problem, we have developed a robust method to
calculate the ACF of the 3D mass-density distribution without tomography.
Assuming the biological mass distribution is isotropic, our method allows for
accurate statistical characterization of the 3D mass-density distribution by ACF
with two data sets: a single projection image by scanning transmission electron
microscopy and a thickness map by atomic force microscopy. Here we present
validation of the ACF reconstruction algorithm, as well as its application to
calculate the statistics of the 3D distribution of mass-density in a region
containing the nucleus of an entire mammalian cell. This method may provide
important insights into architectural changes that accompany cellular processes.
PMID- 28416036
TI - Exploring dementia management attitudes in primary care: a key informant survey
to primary care physicians in 25 European countries.
AB - BACKGROUND: Strategies for the involvement of primary care in the management of
patients with presumed or diagnosed dementia are heterogeneous across Europe. We
wanted to explore attitudes of primary care physicians (PCPs) when managing
dementia: (i) the most popular cognitive tests, (ii) who had the right to
initiate or continue cholinesterase inhibitor or memantine treatment, and (iii)
the relationship between the permissiveness of these rules/guidelines and PCP's
approach in the dementia investigations and assessment. METHODS: Key informant
survey. SETTING: Primary care practices across 25 European countries. SUBJECTS:
Four hundred forty-five PCPs responded to a self-administered questionnaire. Two
step cluster analysis was performed using characteristics of the informants and
the responses to the survey. MAIN OUTCOME MEASURES: Two by two contingency tables
with odds ratios and 95% confidence intervals were used to assess the association
between categorical variables. A multinomial logistic regression model was used
to assess the association of multiple variables (age class, gender, and perceived
prescription rules) with the PCPs' attitude of "trying to establish a diagnosis
of dementia on their own." RESULTS: Discrepancies between rules/guidelines and
attitudes to dementia management was found in many countries. There was a strong
association between the authorization to prescribe dementia drugs and pursuing
dementia diagnostic work-up (odds ratio, 3.45; 95% CI 2.28-5.23). CONCLUSIONS:
Differing regulations about who does what in dementia management seemed to affect
PCP's engagement in dementia investigations and assessment. PCPs who were allowed
to prescribe dementia drugs also claimed higher engagement in dementia work-up
than PCPs who were not allowed to prescribe.
PMID- 28416037
TI - Birth weight, biological maturation and obesity in adolescents: a mediation
analysis.
AB - This study was aimed to investigate associations between birth weight and
multiple adiposity indicators in youth, and to examine potential mediating
effects by biological maturation. This was a school-based study involving 981
Brazilian adolescents aged between 10 and 17 years. Birth weight was reported
retrospectively by mothers. Maturation was estimated by age of peak height
velocity. Adiposity indicators included body mass index (BMI), waist
circumference and percent body fat estimated from triceps and subscapular
skinfolds. Multilevel mediation analyses were performed using the Sobel test,
adjusted for chronological age, gestational age, cardiorespiratory fitness and
socio-economic status. Except for body fat in girls, biological maturation partly
or fully mediated (P<0.05) positive relationships between birth weight with all
other obesity indicators in both sexes with their respective values of indirect
effects with 95% confidence intervals: BMI [boys: 0.44 (0.06-0.82); girls: 0.38
(0.13-0.64)], waist circumference [boys: 1.14 (0.22-2.05); girls: 0.87 (0.26
1.48)] and body fat [boys: 0.60 (0.13-1.07)]. To conclude, birth weight is
associated with elevated obesity risk in adolescence and biological maturation
seems to at least partly mediate this relationship.
PMID- 28416038
TI - The effects of fermentation and enzymatic treatment of pea on nutrient
digestibility and growth performance of broilers.
AB - The present study examined the impacts of native, fermented or enzymatically
treated peas (Pisum sativum L.) inclusion in broiler diets, on growth performance
and nutrient digestibility. For the fermentation process, Madonna pea was mixed
with water (1/1) containing 2.57*108 Bacillus subtilis (GalliPro(r)) spores/kg
pea and then, incubated for 48 h at 30 degrees C. For the enzymatic treatment
process, the used water for dough production contained three enzymes, AlphaGalTM
(alpha-galactosidase), RONOZYME(r) ProAct and VP (protease and pectinases
respectively - DSM, Switzerland) and the pea dough incubated for 24 h at 30
degrees C. Nine corn-wheat-soybean diets were formulated by supplying 10%, 20%
and 30% of the required CP with either native, fermented or enzymatically treated
peas. Performance was recorded weekly and at the end of the experiment (day 35),
apparent ileal digestibility (AID) of CP, amino acids (AA), crude fat, starch,
Ca, P and K were determined. Data were subjected to ANOVA using GLM procedure
with a 3*3 factorial arrangement of treatments. Both processes reduced alpha
galactosides, phytate, trypsin inhibitor activity and resistant starch in peas.
Increasing levels of pea products up to 300 g/kg diet, reduced BW gain and feed
intake (P?0.05). Broilers fed diets containing enzymatically treated pea had the
best feed conversion ratio at day 35. Different types of pea product and their
inclusion levels had no effect on AID of all nutrients. The interaction between
type of the pea products and inclusion levels was significant for AID of starch.
For native pea diets, 10% group showed similar AID of starch to 20% native pea
but it had higher AID than 30% native pea. For fermented and enzymatically
treated groups, all three levels displayed similar AID of starch. In conclusion,
enzymatic treatment and fermentation could improve the nutritional quality of
pea. Inclusion of enzymatically treated pea in broiler diets could improve
broiler performance compared with other pea products while, it displayed neither
positive nor negative impact on nutrient digestibility. The present findings
indicate the feasibility of these processes, particularly enzymatic treatment,
for improving the nutritional quality of pea as a protein source for broiler
nutrition.
PMID- 28416039
TI - Pig cognitive bias affects the conversion of muscle into meat by antioxidant and
autophagy mechanisms.
AB - Slaughter is a crucial step in the meat production chain that could induce
psychological stress on each animal, resulting in a physiological response that
can differ among individuals. The aim of this study was to investigate the
relationship between an animal's emotional state, the subsequent psychological
stress at slaughter and the cellular damage as an effect. In all, 36 entire male
pigs were reared at an experimental farm and a cognitive bias test was used to
classify them into positive bias (PB) or negative bias (NB) groups depending on
their decision-making capabilities. Half of the animals, slaughtered in the same
batch, were used for a complete study of biomarkers of stress, including brain
neurotransmitters and some muscle biomarkers of oxidative stress. After
slaughter, specific brain areas were excised and the levels of catecholamines
(noradrenaline (NA) and dopamine (DA)) and indoleamines (5-hydroxyindoleacetic
acid and serotonin (5HT)) were analyzed. In addition, muscle proteasome activity
(20S), antioxidant defence (total antioxidant activity (TAA)), oxidative damage
(lipid peroxidation (LPO)) and autophagy biomarkers (Beclin-1, microtubule
associated protein I light chain 3 (LC3-I) and LC3-II) were monitored during
early postmortem maturation (0 to 24 h). Compared with PB animals, NB pigs were
more susceptible to stress, showing higher 5HT levels (P<0.01) in the hippocampus
and lower DA (P<0.001) in the pre-frontal cortex. Furthermore, NB pigs had more
intense proteolytic processes and triggered primary muscle cell survival
mechanisms immediately after slaughter (0 h postmortem), thus showing higher TAA
(P<0.001) and earlier proteasome activity (P<0.001) and autophagy (Beclin-1,
P<0.05; LC3-II/LC3-I, P<0.001) than PB pigs, in order to counteract the induced
increase in oxidative stress, that was significantly higher in the muscle of NB
pigs at 0 h postmortem (LPO, P<0.001). Our study is the first to demonstrate that
pig's cognitive bias influences the animal's susceptibility to stress and has
important effects on the postmortem muscle metabolism, particularly on the cell
antioxidant defences and the autophagy onset. These results expand the current
knowledge regarding biomarkers of animal welfare and highlight the potential use
of biomarkers of the proteasome, the autophagy (Beclin-1, LC3-II/LC3-I ratio) and
the muscle antioxidant defence (TAA, LPO) for detection of peri-slaughter stress.
PMID- 28416040
TI - EFFECT OF EARLY SEXUAL DEBUT ON HIGH SCHOOL COMPLETION IN SOUTH AFRICA.
AB - Early sexual debut is of major concern because it is a correlate for health and
economic shocks experienced in adulthood. In South Africa, this concern has
provided impetus for research directed at the HIV and AIDS epidemic, teenage
pregnancy and the effect of adolescent sexual behaviour on persistence in school.
Of interest to the present study is high school completion, which is a well
established empirical barometer of adult socioeconomic opportunities. Using data
from the five waves of the Cape Area Panel Study (CAPS), this paper examines the
association between sexual behaviours initiated in pre- and early adolescence and
high school completion rates. The CAPS study is a longitudinal survey that was
designed to investigate young people's (aged 14-22 years) educational attainment
and sexual behaviours in Cape Town, South Africa. The sample was constituted from
3213 individuals who had initiated sex during their teenage years and the
analysis was undertaken when the youngest cohort was aged 21, an age at which
they should have completed high school if they were on time. Logistic regression
models were fitted separately for males and females. Overall, the results reveal
that early sexual debut is correlated with long-term negative educational
outcomes. Individuals who experience early sexual debut are less likely to
complete high school than their counterparts who make their sexual debut later on
in life. This effect is worse for Africans, who also disproportionately have an
earlier sexual debut than other race groups. Apart from race however, the
findings also reinforce the effect of other demographic factors on high school
completion, namely, place of residence and family socioeconomic status as
measured by parental education and household income. Hence, early sexual debut
adds another layer of inequality and worsens the plight of Africans, females,
those living in rural areas and those who come from low-income families.
PMID- 28416041
TI - Child-targeted fast-food television advertising exposure is linked with fast-food
intake among pre-school children.
AB - OBJECTIVE: To determine whether exposure to child-targeted fast-food (FF)
television (TV) advertising is associated with children's FF intake in a non
experimental setting. DESIGN: Cross-sectional survey conducted April-December
2013. Parents reported their pre-school child's TV viewing time, channels watched
and past-week FF consumption. Responses were combined with a list of FF
commercials (ads) aired on children's TV channels during the same period to
calculate children's exposure to child-targeted TV ads for the following chain FF
restaurants: McDonald's, Subway and Wendy's (MSW). SETTING: Paediatric and Women,
Infants, and Children (WIC) clinics in New Hampshire, USA. SUBJECTS: Parents (n
548) with a child of pre-school age. RESULTS: Children's mean age was 4.4 years;
43.2 % ate MSW in the past week. Among the 40.8 % exposed to MSW ads, 23.3 % had
low, 34.2 % moderate and 42.5 % high exposure. McDonald's accounted for over 70 %
of children's MSW ad exposure and consumption. Children's MSW consumption was
significantly associated with their ad exposure, but not overall TV viewing time.
After adjusting for demographics, socio-economic status and other screen time,
moderate MSW ad exposure was associated with a 31 % (95 % CI 1.12, 1.53) increase
and high MSW ad exposure with a 26 % (95 % CI 1.13, 1.41) increase in the
likelihood of consuming MSW in the past week. Further adjustment for parent FF
consumption did not change the findings substantially. CONCLUSIONS: Exposure to
child-targeted FF TV advertising is positively associated with FF consumption
among children of pre-school age, highlighting the vulnerability of young
children to persuasive advertising and supporting recommendations to limit child
directed FF marketing.
PMID- 28416042
TI - Earthquakes, Fuel Crisis, Power Outages, and Health Care in Nepal: Implications
for the Future.
AB - Earthquakes are a major natural calamity with pervasive effects on human life and
nature. Similar effects are mimicked by man-made disasters such as fuel crises
and power outages in developing countries. Natural and man-made disasters can
cause intangible human suffering and often leave scars of lifelong psychosocial
damage. Lessons from these disasters are frequently not implemented. The main
objective of this study was to review the effects of the 2015 earthquakes, fuel
crisis, and power outages on the health services of Nepal and formulate
recommendations for the future. The impacts of earthquakes on health can be
divided into immediate, intermediate, and long-term effects. Power outages and
fuel crises have health hazards at all stages. It is imperative to understand the
temporal effects of earthquakes, because the major needs soon after the
earthquake (emergency care) are vastly different from long-term needs such as
rehabilitation and psychosocial support. In Nepal, the inadequate and nearly
nonexistent specialized health care at the peripheral level claimed many lives
during the earthquakes and left many people disproportionately injured.
Preemptive strategies such as mobile critical care units at primary health
centers, intensive care training for health workers, and alternative plans for
emergency care must be prioritized. Similarly, infrastructural damage led to poor
sanitation, and alternative plans for temporary settlements (water supply, food,
settlements logistics, space for temporary settlements) must be in place where
the danger of disease outbreak is imminent. While much of these strategies are
implementable and are often set as priorities, long-term effects of earthquakes
such as physical and psychosocial supports are often overlooked. The burden of
psychosocial stresses, including depression and physical disabilities, needs to
be prioritized by facilitating human resources for mental health care and
rehabilitation. In addition, inclusion of mental health and rehabilitation
facilities in government health care services of Nepal needs to be prioritized.
Similarly, power outages and fuel crises affect health care disproportionately.
In the current context where permanent solutions may not be possible, mitigating
health hazards, especially cold chain maintenance for essential medicines and
continuation of life-saving procedures, are mandatory and policies to regulate
all health care services must be undertaken. (Disaster Med Public Health
Preparedness. 2017;11:625-632).
PMID- 28416044
TI - Treatment of PTSD-Related OSA With CPAP is Associated With Only a Modest
Improvement in PTSD: Possible Adjunctive Treatment With Mood Stabilizers.
PMID- 28416043
TI - Delaying Middle School and High School Start Times Promotes Student Health and
Performance: An American Academy of Sleep Medicine Position Statement.
AB - ABSTRACT: During adolescence, internal circadian rhythms and biological sleep
drive change to result in later sleep and wake times. As a result of these
changes, early middle school and high school start times curtail sleep, hamper a
student's preparedness to learn, negatively impact physical and mental health,
and impair driving safety. Furthermore, a growing body of evidence shows that
delaying school start times positively impacts student achievement, health, and
safety. Public awareness of the hazards of early school start times and the
benefits of later start times are largely unappreciated. As a result, the
American Academy of Sleep Medicine is calling on communities, school boards, and
educational institutions to implement start times of 8:30 AM or later for middle
schools and high schools to ensure that every student arrives at school healthy,
awake, alert, and ready to learn.
PMID- 28416045
TI - Hypnotics and the Risks of Dementia.
PMID- 28416046
TI - Challenges in the Management of Sleep Apnea and PTSD: Is the Low Arousal
Threshold an Unrealized Target?
PMID- 28416047
TI - Clarifying the Role of Hypoxia in Obstructive Sleep Apnea as a Potential
Promulgator of Atrial Fibrillation in Ischemic Stroke.
PMID- 28416048
TI - AASM Scoring Manual Updates for 2017 (Version 2.4).
PMID- 28416049
TI - A Restless Farewell in Changing Times: Advice for the Field of Sleep Medicine.
PMID- 28416050
TI - Proteomic analysis of the endometrium during early pregnancy in the domestic pig.
AB - Reproductive processes in domestic pigs have been studied extensively. Pigs are
one of the main sources of meat for human consumption and are an established
model for investigations into mammalian, including human, reproductive
physiology. Studies of the uterus during early pregnancy will lead to a better
understanding of mechanisms governing pregnancy. Proteomics provides the
possibility to explore endometrial functions in an unbiased way. The aim of the
study was to compare endometrium harvested from Days 12-13 and 15-16 of pregnancy
with the corresponding days of the oestrous cycle. We identified endometrial
proteins that are unique to the early stages of pregnancy (Days 12-13 and 15-16).
Twenty-one proteins were identified that were uniquely expressed on the selected
days of pregnancy or the oestrous cycle. Out of 21 identified proteins, 14
referred to the pregnancy periods. Systemic analysis of the identified proteins
revealed cell adhesion and cytoskeletal organisation as two of the major
functions, both of which are important for the establishment and maintenance of
pregnancy. Thrombospondin 1 expression was validated using western blotting
analysis and the results suggest its involvement in the adhesiveness of the
embryo during the peri-implantation period in pigs.
PMID- 28416051
TI - [Mirror syndrome is a rare complication in pregnancy, characterized by oedema and
hydrops fetalis].
AB - We describe a case of mirror syndrome. A 41-year-old woman, para 4, was referred
to hospital at 32 weeks of gestational age with excessive oedema. She developed
oliguria, mild hypertension and proteinuria. Fetal ultrasound confirmed severe
hydrops fetalis. Intrauterine pleural drainage was performed without improvement
of the condition. Since maternal symptoms worsened, a caesarean section was
performed at 34 weeks with delivery of a live hydropic girl who died after 17
hours. Maternal symptoms decreased four days after delivery with full recovery
two weeks post-partum.
PMID- 28416052
TI - [A 38-year-old woman with an anovaginal fistula after consensual penile anal
intercourse].
AB - In this case report a 38-year-old woman was admitted to hospital with anal
bleeding and perianal pain after a consensual vaginal intercourse followed by an
anal intercourse during which she felt a sudden profound pain. Nine days later
she was diagnosed with an anovaginal fistula. A diverting sigmoideostomy was
performed, and spontaneous healing was awaited. Rectovaginal fistula without
concomitant anal sphincter injury as a result of consensual penile anal
intercourse is an extremely rare occurrence, described only once previously.
PMID- 28416053
TI - [Treatment of anaphylactic schock in pregnant women].
AB - This is an update on the treatment of anaphylactic shock in pregnant women. Most
guidelines recommend adrenaline as first-line treatment in all patients, but in
pregnant patients some recommend ephedrine due to a potential risk of utero
placental hypoperfusion with adrenaline. However, ephedrine is a less potent
vasopressor than adrenaline and does not possess the same anti-inflammatory or
broncho-dilating effects. As immediate and correct treatment is essential for
both the maternal and the fetal outcome, adrenaline should be first-line
treatment also in pregnant women.
PMID- 28416054
TI - [Combined endoscopic laparoscopic colon polypectomy].
AB - Combined endoscopic laparoscopic surgery (CELS) is a novel technique for
resection of benign colon polyps, which are not amenable for endoscopic
resection. A review of ten studies including 416 patients shows that polyps were
successfully resected in 65-97% of the patients. Polyp recurrence after CELS is
low, and the frequency of adenocarcinoma is comparable with the frequency in
large polyps (> 2 cm) resected endoscopically. CELS can be performed for a
variety of indications but should be done after renewed endoscopy. Due to the
risk of cancer it should only be performed in specialized centres.
PMID- 28416055
TI - [Akut infantilt haemoragisk odem].
PMID- 28416056
TI - ?
PMID- 28416057
TI - ?
PMID- 28416058
TI - ?
PMID- 28416059
TI - [Amelanotisk malignt melanom pa en finger].
PMID- 28416060
TI - [Gas-filled liver metastases caused by Clostridium septicum sepsis].
AB - In this case report a 73-year-old male with liver-metastatic colon cancer was
admitted to hospital due to severe abdominal pain merely four days after
receiving chemotherapy including epidermal growth factor receptor inhibitors. An
acute computed tomography revealed gas-filled liver metastases with two possible
diagnoses of either a rapid tumour response resulting in tumour necrosis or
severe bacterial infection involving liver metastases. Moreover, the patient had
an anaerobic infection with Clostridium septicum, and despite relevant treatment
he died within 12 hours after admission.
PMID- 28416061
TI - [Bouveret's syndrome - a rare complication in connection with cholecystolithiasis
and a variant of gallstone ileus].
AB - Bouveret's syndrome is a very rare complication to cholecystolithiasis resulting
in gallstone ileus. It is caused by ectopic gallstones in the duodenum due to a
bilioenteric fistula. Symptoms may include vomiting and upper abdominal pains.
The condition is associated with high mortality, making it important to
recognize. The treatment includes surgical removal of the gallstone. However, the
optimal therapeutic approach has still not been found. In this case report a 59
year-old female with Bouveret's syndrome is presented.
PMID- 28416062
TI - [Growing pains are well-known, but the cause remains unclear].
AB - A common complaint from children is growing pains: a mild to severe pain located
primarily in the legs and being most intense in evenings and during sleep. The
diagnosis is based on the characteristics of the pain and careful clinical
examination. The pain disappears as the child grows up. Research has suggested
that the pain occurs more often in children who suffer from vitamin D deficiency,
low bone density, low pain threshold, restless legs syndrome and in children who
were breastfed for less than 40 days from birth. There are not yet any firm
conclusions about the aetiology.
PMID- 28416063
TI - [Repetitive transcranial magnetic stimulation treatment for post-traumatic stress
disorder].
AB - Approximately 10% of combat soldiers and 30% of rape victims develop post
traumatic stress disorder (PTSD). Repetitive transcranial magnetic stimulation
(rTMS) is already known to be safe in depression treatment. Research results of
the past 15 years indicate that rTMS induced to the right dorsolateral prefrontal
cortex may have a potential to treat the symptoms of PTSD. Furthermore, high
frequency rTMS seems to be superior to low-frequency rTMS. The effect of rTMS on
PTSD symptoms could be mediated by increasing the level of brain-derived
neurotrophic factor.
PMID- 28416065
TI - ?
PMID- 28416064
TI - [Evaluation and treatment of patients after caustic ingestion].
AB - This article presents recommendations regarding early management of patients
after intake of corrosive chemicals, based on best evidence and clinical
experience. Risk assessment built on clinical history, presentation and endoscopy
is discussed as well as initial treatment, surgical appraisal and observation.
Controversy still surrounds the need for endoscopy in asymptomatic patients, the
use of computed tomography in assessing the severity of lesions as well as
pharmacological treatment for preventing strictures.
PMID- 28416066
TI - ?
PMID- 28416067
TI - ?
PMID- 28416068
TI - [Treatment with low-dose acetylsalicylic acid can reduce risk of pre-eclampsia in
high-risk pregnant women].
AB - Pre-eclampsia is a major contributor to perinatal morbidity and mortality. Large
studies of high-risk pregnant women have shown reduced risk of developing pre
eclampsia when they are treated with low-dose acetylsalicylic acid in early
pregnancy. Treatment is also effective in preventing intrauterine growth
restriction, preterm birth and perinatal death. No major side effects, including
risk of malformations or miscarriage, are reported. It is important that general
practitioners are aware of women who have an increased risk of developing pre
eclampsia, so that treatment with 100 mg of acetylsalicylic acid can be started
early in pregnancy.
PMID- 28416069
TI - [Dietary treatment of medically refractory epilepsy in children and adolescents].
AB - Ketogenic diet (KD) is used worldwide in the treatment of medically refractory
epilepsy. Since the introduction of KD in the early 1900s, new approaches such as
medium-chain triglyceride ketogenic diet, modified Atkins diet and low glycaemic
index treatment have been suggested as alternative treatments. Several studies
have documented significant seizure reduction from all four diets. The aim of
this article is to give an overview of the effect of dietary treatment and to
discuss advantages in initiating dietary treatment as an early treatment instead
of as a last option.
PMID- 28416070
TI - [Intentional suicide with cyclizine].
AB - Cyclizine is an antihistamine with a sedative effect. In Denmark it is an over
the-counter drug, whereas it is a prescription drug in many other countries. It
possesses anticholinergic and antiemetic properties, although the exact mechanism
of action is unknown. At doses greater than 5 mg/kg potent side effects of
anticholinergic character can be expected. This case report is a description of
an intentional suicide with a dose greater than 70 mg/kg.
PMID- 28416071
TI - [Acute upper airway obstruction caused by a multinodular goitre after
tracheotomy].
AB - This case report illustrates how a multinodular goitre caused acute airway
obstruction in a multitrauma 66-year-old male after tracheotomy. The patient had
no symptoms of the goitre before the tracheotomy but developed subglottic airway
obstruction at the time of decannulation. He underwent a subacute total
thyroidectomy which removed the obstructive symptoms. A weakening of the tracheal
tube followed by the tracheotomy possibly caused the tracheal stenosis in
combination with the goitre.
PMID- 28416072
TI - [A Scandinavian guideline for initial management of minimal, mild and moderate
head trauma in children].
AB - The Scandinavian Neurotrauma Committee has recently published an evidence- and
consensus-based guideline for the management of minor and moderate head trauma in
children. They aim is to select children for computed tomography (CT) scan,
observation or early discharge, with the attempt to reduce the number of CT scans
in children without missing any significant intracranial injury in need for
treatment. A flow chart of the guidelines and a help sheet has been developed for
clinical use. Suggestions for in-hospital observation and parental information
are also presented. We present the guideline in Danish.
PMID- 28416073
TI - [The implications of using different body mass index references in children and
adolescents].
AB - To classify children as overweight or obese, their body mass index (BMI) must be
compared with a growth reference and be accompanied by a clinical assessment. In
Denmark, there is a lack of consensus on which BMI reference to use; a mix of
national and international references are used in clinics, hospitals and research
institutions. In this article, the implications of using different references are
illustrated with Danish data. The comparisons show that the references yield
different prevalences of overweight in a non-predictable way, making comparisons
and monitoring challenging.
PMID- 28416074
TI - [The stratified H-index makes scientific impact transparent].
AB - The H-index is widely used to quantify and standardize researchers' scientific
impact. However, the H-index does not account for the fact that co-authors rarely
contribute equally to a paper. Accordingly, we propose the use of a stratified H
index to measure scientific impact. The stratified H-index supplements the
conventional H-index with three separate H-indices: one for first authorships,
one for second authorships and one for last authorships. The stratified H-index
takes scientific output, quality and individual author contribution into account.
PMID- 28416075
TI - Muscle strength rather than muscle mass is associated with osteoporosis in older
Chinese adults.
AB - BACKGROUND: Assessment of the association of muscle strength and muscle mass with
osteoporosis (OP) is of special interest as muscles are a potential target for
interventions (i.e., strength training). METHODS: A cross-sectional descriptive
study encompassing people aged >= 60 years (average age: 66.9 +/- 6.2 years; men,
n = 516; women, n = 652) in the Hangu area of Tianjin, China. The study
populations were invited to participate in a comprehensive geriatric assessment.
OS was identified by measuring the calcaneal using a quantitative ultrasound and
a T score of less than -2.5. Muscle characteristics included grip strength and
appendicular skeletal muscle mass (ASM). RESULTS: The prevalence of OS in this
study was 61.6% (male 52.1%, female 69.1%). Grip strength was negatively related
to OS and after adjusting for all other variables, higher grip strength was found
to be associated with a lower OS risk (p = 0.023). ASM/height2 was not associated
with OS (p = 0.205). CONCLUSION: Based on our study, muscle strength rather than
muscle mass is negatively associated with OS in older people; thus, we should pay
more attention to muscle strength training in the early stage of the OS.
PMID- 28416076
TI - Sweat allergy: Extrinsic or intrinsic?
AB - Sweat is an exacerbation factor in atopic dermatitis (AD) in all age groups. A
body core temperature elevation with sweating triggers cholinergic urticaria
(CholU). We recently reported that AD symptoms are improved by tannic acid
containing spray, which suppresses the basophil histamine release induced by semi
purified sweat antigen in vitro, and by showering, which removes antigens in
sweat from the skin surface. Sweat contains small amount of proteins including
proteases, protease inhibitors, and anti-microbial peptides. We finally
identified MGL_1304 secreted by Malassezia (M.) globosa as a major histamine -
releasing antigen in human sweat. MGL_1304 is a 17-kDa protein in sweat that
elicits almost the highest histamine - release activity from basophils of
patients with AD and CholU among antigens derived from Malassezia species.
Moreover, serum levels of anti-MGL_1304 IgE were significantly higher in patients
with AD and CholU than in normal controls. The recombinant protein produced by
Pichia pastoris possessed comparable allergenicity to native MGL_1304. We found a
monoclonal IgE antibody against MGL_1304 which did not elicit histamine release
from sensitized mast cells. Desensitization therapy using autologous sweat, or
MGL_1304 purified from culture of M. globosa or its cognates might be beneficial
for patients with intractable CholU due to sweat allergy.
PMID- 28416078
TI - Corrigendum to "Caring for children with intellectual disabilities part 1:
Experience with the population, pain-related beliefs, and care decisions" [Res.
Dev. Disabil. 62 (2017) 197-208].
PMID- 28416077
TI - Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent
Suppression of Caveolae-Mediated Transcytosis.
AB - The blood-brain barrier (BBB) provides a constant homeostatic brain environment
that is essential for proper neural function. An unusually low rate of vesicular
transport (transcytosis) has been identified as one of the two unique properties
of CNS endothelial cells, relative to peripheral endothelial cells, that maintain
the restrictive quality of the BBB. However, it is not known how this low rate of
transcytosis is achieved. Here we provide a mechanism whereby the regulation of
CNS endothelial cell lipid composition specifically inhibits the caveolae
mediated transcytotic route readily used in the periphery. An unbiased lipidomic
analysis reveals significant differences in endothelial cell lipid signatures
from the CNS and periphery, which underlie a suppression of caveolae vesicle
formation and trafficking in brain endothelial cells. Furthermore, lipids
transported by Mfsd2a establish a unique lipid environment that inhibits caveolae
vesicle formation in CNS endothelial cells to suppress transcytosis and ensure
BBB integrity.
PMID- 28416080
TI - Molecular identification and immunological characteristics of goose suppressor of
cytokine signaling 1 (SOCS-1) in vitro and vivo following DTMUV challenge.
AB - Purpose suppressor of cytokine signaling 1 (SOCS-1) is inducible feedback
inhibitors of cytokine signaling and involved in viral infection through
regulation of both innate and adaptive immunity. In this study, we firstly cloned
SOCS-1 (goSOCS-1) from duck Tembusu virus (DTMUV) infected goose. The full-length
sequence of goSOCS-1 ORF is 624bp and encoded 108 amino acids. Structurally, the
mainly functional regions (KIR, SH2, SOCS-box) were conserved between avian and
mammalian. The tissues distribution data showed SOCS-1 highly expressed in immune
related tissues (SP, LU, HG) of both gosling and adult goose. Moreover, the
goSOCS-1 transcripts were induced by goIFNs in GEFs and by TLR ligands in PBMCs.
Notably, upon DTMUV infection, highly expression level of goSOCS-1 was detected
in vitro and in vivo with high viral load. Our results indicated that goSOCS-1
might involve in both innate and adaptive antiviral immunity of waterfowl.
PMID- 28416079
TI - Management of Childhood Congenital Adrenal Hyperplasia-An Integrative Review of
the Literature.
AB - Congenital adrenal hyperplasia (CAH) is an endocrine condition that requires
parents to administer steroids up to three times daily, supplementing maintenance
doses with oral or injectable doses during times of illness. The purpose of this
integrative review was to explore the management, care, and associated health
issues for children with CAH and the family response to the condition. Four
literature indexes were searched, with 39 articles included. Four themes emerged:
(a) Health- and Development-Related Issues, (a) Effects of Excess Androgens, (c)
Life Experience of CAH, and (d) Managing and Averting Adrenal Crisis. Families
having a child with CAH face complex concerns related their child's growth, the
fear of adrenal crisis events, and the consequences of atypical genitalia for
affected girls. Future studies should focus on interventions that provide
guidelines to increase parental preparedness in managing adrenal crises and
creating support systems for affected girls.
PMID- 28416081
TI - Reversible cerebral vasoconstriction syndrome combined with posterior reversible
encephalopathy syndrome after heart transplantation.
AB - Reversible cerebral vasoconstriction syndrome (RCVS) combined with posterior
reversible encephalopathy syndrome (PRES) is a rare complication in patients
treated with immunosuppressants. A 52-year-old male patient presented with
seizures after heart transplantation. The patient was suspected of having PRES on
brain images. Despite the strict blood pressure control, the patient presented
with altered mentality and the brain images showed a newly developed large acute
infarction. Digital subtraction angiography (DSA) revealed the classic "sausage
on a string" appearance of the cerebral arteries - potential feature of RCVS. To
our knowledge, this is the first case report to describe RCVS combined with PRES
after heart transplantation.
PMID- 28416082
TI - Final diagnosis of patients with clinically suspected vestibular neuritis showing
normal caloric response.
AB - Vestibular neuritis is one of the most common peripheral causes of acute
vestibular syndrome, of which the diagnosis is generally based on a comprehensive
interpretation of clinical and laboratory findings following reasonable exclusion
of other disorders. This study aimed to investigate the final diagnosis of
patients admitted to hospital under the clinical impression of vestibular
neuritis who showed no unilateral caloric paresis. Forty-five patients who
visited the emergency department with isolated acute spontaneous vertigo were
included. Among them, six patients (13%) developed definitive spontaneous vertigo
lasting longer than 20min again after discharge from hospital, accompanied by
hearing loss, which was audiometrically documented, leading to a final diagnosis
of definite Meniere's disease. Nine patients (20%) revisited our clinic with
recurrent episodic vertigo without any documented hearing loss or auditory
symptoms such as hearing loss, tinnitus or ear fullness, which led to a final
diagnosis of possible Meniere's disease. In four patients (9%), initial
spontaneous vertigo and nystagmus changed to positional vertigo and nystagmus on
the second hospital day. In 26 patients (58%), neither another episode of vertigo
nor auditory symptoms developed during follow-up period (7-92months), a condition
to which the authors gave an arbitrary diagnosis of "mild unilateral vestibular
deficit". In conclusion, patients admitted to hospital under clinical impression
of vestibular neuritis may have various final diagnoses, and "mild unilateral
vestibular deficit" was the most common final diagnosis among patients who did
not meet the diagnostic criteria of vestibular neuritis.
PMID- 28416083
TI - Prevalence and Occupation of Patients Presenting With Dysphonia in the United
States.
AB - OBJECTIVE: Voice disorders are common conditions that may have a significant
impact on patient quality of life, yet their prevalence and epidemiology are
poorly documented. In this study, we estimated the prevalence, demographics, and
occupation of patients with dysphonia. METHODS: Using the Commercial and Medicare
MarketScan databases of 146.7 million lives (2008-2012), the prevalence of
dysphonia was estimated. Patient demographics and industry occupation were
evaluated. Prevalence estimates overall and by industry were made using Medical
Expenditure Panel Survey. Industry estimates were compared with US government
employment statistics to assess differences between dysphonia and the general
population. RESULTS: A gradual increase in the diagnosis of dysphonia was noted
from 1.3% to 1.7% of the population from 2008 to 2012, with an associated
increase in the diagnosis of acute laryngitis, the largest diagnostic category. A
strong correlation was present between diagnosis and age, with acute laryngitis
more common in the younger populations and malignancies in older ages. Benign
neoplasms were more prevalent in the service industry, with 2.6 times increased
likelihood compared with the general population, and malignancies were more
prevalent in the manufacturing industry, with 1.4 times increased likelihood.
Almost 3 million laryngoscopies and stroboscopies were performed with $900
million in costs. CONCLUSION: Prevalence rates of the diagnosis of dysphonia are
increasing and are associated with large healthcare costs. Prevalence rates also
differ somewhat between industries, and there appears to be a higher percentage
of malignant neoplasms in the manufacturing industry and benign neoplasms in the
service industry.
PMID- 28416084
TI - A conceptual framework for negotiating public involvement in municipal waste
management decision-making in the UK.
AB - The technical expertise that politicians relied on in the past to produce cost
effective and environmentally sound solutions no longer provides sufficient
justification to approve waste facilities. Local authorities need to find more
effective ways to involve stakeholders and communities in decision-making since
public acceptance of municipal waste facilities is integral to delivering
effective waste strategies. This paper presents findings from a research project
that explored attitudes towards greater levels of public involvement in UK waste
management decision-making. The study addressed questions of perception,
interests, the decision context, the means of engagement and the necessary
resources and capacity for adopting a participatory decision process. Adopting a
mixed methods approach, the research produced an empirical framework for
negotiating the mode and level of public involvement in waste management decision
making. The framework captures and builds on theories of public involvement and
the experiences of practitioners, and offers guidance for integrating analysis
and deliberation with public groups in different waste management decision
contexts. Principles in the framework operate on the premise that the decision
about 'more' and 'better' forms of public involvement can be negotiated, based on
the nature of the waste problem and wider social context of decision-making. The
collection of opinions from the wide range of stakeholders involved in the study
has produced new insights for the design of public engagement processes that are
context-dependent and 'fit-for-purpose'; these suggest a need for greater
inclusivity in the case of contentious technologies and high levels of
uncertainty regarding decision outcomes.
PMID- 28416085
TI - Delamination mechanism study of large size waste printed circuit boards by using
dimethylacetamide.
AB - Present work investigates the recycling of waste printed circuit boards (PCBs) by
cracking of its multi-layered structure by using dimethylacetamide (DMA). The
study shows that cracking and separation of layers of PCBs increases as the
temperature increases; and decreases as the surface area of PCBs increases. After
separation of layers, the used solvent was analyzed by proton and carbon nuclear
magnetic resonance spectroscopy (NMR) to understand the dissolution phenomenon of
resin. Further, NMR and Fourier transform infrared spectroscopy analysis of DMA
sample after 1h, 2h, 3h, 4h and 8h of reaction with PCBs at 433K and PCB:DMA
ratio (wt/vol) of 3:10 has been carried out to investigate the mechanism of
dissolution of resin. These studies revealed that hydroxyl group of PCBs
polymeric chain participates in hydrogen bonding with parent carbonyl group of
DMA molecule that results in the solvation of resin. Possible chemical reaction
based on the above finding has been discussed. Using this technique, separation
of the metallic fraction without application of any energy intensive mechanical
pre-processing is possible.
PMID- 28416086
TI - History of Depression in Lung Cancer Patients: Impact of Delay.
AB - AIMS: To examine the influence of a history of depression in the process of
diagnostic evaluation and the choice of treatment in lung cancer. MATERIALS AND
METHODS: The analysis was based on all patients with non-small cell lung cancer
who were registered in 2008-2014; in total, 27 234 patients. To estimate the
effect of depression on the diagnostic process and the choice of treatment in
lung cancer we fitted a logistic regression model and a Cox regression model
adjusting for age, gender, resection and stage. RESULTS: Depression in a
patient's anamnesis had no significant effect on the delay in diagnostic
evaluation (hazard ratio = 0.99 with 95% confidence interval 0.90; 1.09).
Patients with a history of periodic depression had a 33% lower treatment rate
(odds ratio = 0.66 with 95% confidence interval 0.51; 0.85) than patients without
a history of depression. CONCLUSIONS: Our study shows that patients with a
history of periodic depression need special attention when diagnosed with lung
cancer.
PMID- 28416087
TI - The impact of joint angle and movement velocity on sex differences in the
functional hamstring/quadriceps ratio.
AB - BACKGROUND: Females are two to eight times more likely to suffer a non-contact
injury compared with males thus the purpose of this study was to explore the
influence of joint angle and movement velocity on sex differences in the
functional hamstring to quadriceps ratio (H/QFUNC). METHODS: Isokinetic
concentric and eccentric torque were determined in 110 participants (55 males and
55 females) through a 90 degrees range of movement at 60, 120, and 240 degrees
/s. Testing was performed with the hip flexed at 10 degrees . The H/QFUNC was
determined at three specific joint angles (15, 30 and 45 degrees flexion) and
where peak torque occurred for concentric knee extension. RESULTS: A significant
interaction effect (P<0.01) for sex and joint angle was observed with women
demonstrating a lower H/QFUNC than males, especially at more extended knee
positions. A significant sex by velocity interaction (P<0.01) indicated a lower
H/QFUNC in women as velocity increased. Significant main effects (P<0.01)
indicated that irrespective of sex the H/QFUNC increased as the knee extends and
velocity increases. CONCLUSION: Given the reduced H/QFUNC in females compared to
males at more extended knee positions and faster velocities, this may contribute
to the observed sex bias in reported injury rates.
PMID- 28416089
TI - Recurrent Stroke and Early Mortality in an Urban Medical Unit in Cameroon.
AB - BACKGROUND: Data on stroke mortality in recurrent strokes in the context of
limited acute stroke care and secondary stroke prevention within Africa are very
scant. We investigated the risk of in-hospital death in patients with recurrent
stroke in the medical department of the Yaounde Central Hospital in Cameroon.
METHODS: Admission and discharge registries, and patient files for the period
1999-2012, were reviewed for evidence of admission for stroke, recurrent stroke,
and in-hospital death. Mortality was compared between recurrent and first-ever
stroke overall, and heterogeneities across major subgroups were assessed via
interaction tests. RESULTS: Out of 1678 participants included in the final
analytic sample, 243 (14.5%) had recurrent stroke. Our first-ever stroke
participants were older (median age 65.0 years versus 62.0 years, P = .024), had
a worse stroke risk profile (prevalent diabetes 17.5% versus 12.0%, P = .018;
atrial fibrillation 3.7% versus 1.1%, P = .002; hypertension 91.7% versus 63.9%,
P < .0001), and were smokers. Sixty-five deaths (20.6%) occurred among
participants with recurrent stroke and 281 (19.6%) among first-ever stroke
participants (P = .013). The adjusted odds ratio of mortality from recurrent
stroke was 1.43 (95% CI: 1.03-1.99). CONCLUSION: Stroke survivors have a 43%
higher risk of dying after a recurrent stroke compared to those with first-ever
stroke, against a background of unfavorable stroke risk profile.
PMID- 28416088
TI - A novel MIS technique for posterior cruciate ligament avulsion fractures.
AB - OBJECTIVE: Open surgical approaches to treat tibial avulsion fractures of the
posterior cruciate ligament (PCL) often use large incisions involving extensive
muscle dissection and retraction. The objective of this study was to describe a
new mini-invasive approach targeting the fractured zone, to minimize surgical
dissection and improve recovery and rehabilitation. METHODS: The new approach was
used in 15 males and seven females with isolated PCL avulsions. The length of the
surgical incision, surgical time, need for conversion to open technique, visual
analog scores (VAS) and duration of hospital stay were studied to assess the
efficacy, learning curve and advantages of the new technique. Neurovascular
complications were recorded. At the two-year follow-up, International Knee
Documentation Committee (IKDC) scores were recorded to assess function. RESULTS:
Patients were followed up for a mean of 29months (range: 34-41). The mean length
of the incision was 4.1cm (range: 3.4 to five) measured at the end of the
procedure. None of the patients required conversion to an open technique and no
neurovascular complications were recorded. The mean surgical time was 40min
(range: 25-50). The mean VAS on discharge was 2.2 (range: one to four) and
patients stayed at the hospital for a mean of 2.2days (range: one to three). The
mean IKDC score at one-year post surgery was 86.4 (range: 83.9-90.8).
CONCLUSIONS: The new mini-invasive targeted approach provides adequate exposure
for performing internal fixation of PCL avulsion fractures without the surgical
morbidity associated with conventional open surgical approaches. The procedure is
safe, fast and does not require a long learning curve.
PMID- 28416090
TI - Clipping in Awake Surgery as End-Stage in a Complex Internal Carotid Artery
Aneurysm After Failure of Multimodal Endovascular and Extracranial-Intracranial
Bypass Treatment.
AB - BACKGROUND: Intracranial carotid artery aneurysm can be treated via microsurgical
or endovascular techniques. The optimal planning is the result of the careful
patient selection through clinical, anatomic, and angiographic analysis. CLINICAL
PRESENTATION: We present a case of ruptured internal carotid artery (ICA)
aneurysm that became a complex aneurysm after failure of multi-endovascular and
surgery treatment. We describe complete trapping in awake craniotomy after
failure of coiling, stenting, and bypassing. CONCLUSIONS: ICA aneurysms could
become complex aneurysms following multi-treatment failure. Endovascular
approaches to treat ICA aneurysms include coiling, stenting, flow diverter
stenting, and stenting-assisted coiling technique. The role of surgery remains
relevant. To avoid severe neurologic deficits, recurrence, and the need of
retreatment, a multidisciplinary discussion with experienced endovascular and
vascular neurosurgeons is mandatory in such complex cases.
PMID- 28416091
TI - Corrigendum to "Glucose enhances tilapia against Edwardsiella tarda infection
through metabolome reprogramming" [Fish and Shellfish Immunol. 61 (2017) 34-43].
PMID- 28416092
TI - Cytokines and C-reactive protein alterations with respect to cognitive impairment
in schizophrenia and bipolar disorder: A systematic review.
AB - BACKGROUND: The aim of this article was to perform a systematic review of studies
investigating the association between peripheral levels of cytokines and C
reactive protein (CRP), cytokine gene polymorphisms and cognition in patients
with schizophrenia and bipolar disorder (BD). METHODS: The following databases:
PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source:
Nursing/Academic Edition databases were searched according to the PRISMA
guidelines. We included studies that investigated the association between
peripheral levels of CRP and cytokines, cytokine gene polymorphisms and cognitive
performance in schizophrenia and/or BD patients. Subsequently, quality assessment
of eligible publications was performed. Results were synthesized by discussing
main findings around correlations between inflammatory markers and cognition.
RESULTS: Most consistent results indicate worse cognitive performance in
schizophrenia patients with higher CRP levels. Less consistent evidence suggests
better cognitive functioning of schizophrenia patients with higher levels of
tumour necrosis factor-alpha (TNF-alpha). Evidence for the involvement of other
cytokines in cognitive impairment in patients with schizophrenia is less
convincing due to discordant results or scarcity of studies. Due to low number of
studies, it is difficult to draw conclusions on the involvement of CRP and
cytokine alterations in the development of cognitive deficits in BD. Single
studies suggest the role of CRP, interleukin(IL)-1 receptor antagonist, IL-6 and
TNF-alpha with its receptors in the development of cognitive impairment in BD.
CONCLUSIONS: Peripheral inflammation might be related to cognitive deficits in
schizophrenia and BD. Unequivocal conclusions cannot be made due to
methodological heterogeneity and low number of studies investigating particular
cytokines.
PMID- 28416093
TI - The role of cognitive functioning in the relationship between childhood trauma
and a mixed phenotype of affective-anxious-psychotic symptoms in psychotic
disorders.
AB - Cognitive impairments in patients with psychotic disorder have been associated
with poor functioning and increased symptom severity. Furthermore, childhood
trauma (CT) exposure has been associated with worse cognitive functioning as well
as co-occurrence of affective-anxious-psychosis symptoms or a 'mixed phenotype of
psychopathology' (MP), which in turn is associated with greater symptom severity,
and poor functioning. This study aims to evaluate if cognition could be
associated with CT/MP. 532 patients with non-affective psychotic patients were
assessed on CT, symptom profile, cognition, functioning, and symptom severity at
baseline and 3 and 6-year follow-up. Four subgroups were made according to trauma
exposure (CT- or CT+) and presence of a mixed phenotype (MP- or MP+): CT-/MP
(n=272), CT-/MP+ (n=157), CT+/MP- (n=49), and CT+/MP+ (n=54). Mixed-effects
multilevel regression, linear regression, and Tobit analyses were performed.
Patients with both CT and MP showed lower verbal learning and memory than CT-/MP+
individuals (p<0.001). No other significant differences were found among the 4
subgroups. No cognitive decline was found at follow-up, neither in the CT+/MP-
nor in CT-/MP- group. Lower cognition was not associated with increased symptom
severity or poor functioning at follow-up, neither in the CT+/MP- nor in CT-/MP-
group. Although cognitive impairments and CT may be related to clinical or
functional features of psychotic disorder, and cognitive functioning could be
affected by CT exposure, cognition does not discriminate subgroups of patients
stratified by CT exposure and MP.
PMID- 28416094
TI - The effect of tDCS on auditory hallucination and P50 sensory gating in patients
with schizophrenia: A pilot study.
PMID- 28416095
TI - Self- and other-agency in people with passivity (first rank) symptoms in
schizophrenia.
AB - Individuals with passivity (first-rank) symptoms report that their actions,
thoughts and sensations are influenced or controlled by an external (non-self)
agent. Passivity symptoms are closely linked to schizophrenia and related
disorders yet they remain poorly understood. One dominant framework posits a role
for deficits in the sense of agency. An important question is whether deficits in
self-agency can be differentiated from other-agency in schizophrenia and
passivity symptoms. This study aimed to evaluate self- and other-agency in 51
people with schizophrenia (n=20 current, 10 past, 21 no history of passivity
symptoms), and 48 healthy controls. Participants completed the projected hand
illusion (PHI) with active and passive movements, as well as immediate and
delayed visual feedback. Experiences of agency and loss of agency over the
participant's hand and the image ('the other hand') were assessed with a self
report questionnaire. Those with passivity symptoms (current and past) reported
less difference in agency between active and passive movements on items assessing
agency over their own hand (but not agency over the other hand). Relative to the
healthy controls, the current and never groups continued to experience the
illusion with delayed visual feedback suggesting impaired timing mechanisms
regardless of symptom profile. These findings are consistent with a reduced
contribution of proprioceptive predictive cues to agency judgements specific to
self representations in people with passivity symptoms, and a subsequent reliance
on external visual cues in these judgements. Altogether, these findings emphasise
the multifactorial nature of agency and the contribution of multiple impairments
to passivity symptoms.
PMID- 28416096
TI - Treatment outcomes of archwise distraction osteogenesis in mandibular
dentoalveolar retrognathia cases.
AB - The aim of this study was to describe the treatment of class II malocclusion by
sagittal advancement of the alveolar bone in the symphyseal area using an
intraoral archwise distractor device and to determine the effects of this method
on the dentoalveolar complex. Fifteen patients (10 female, five male) aged 16-20
years with a class II division 2 malocclusion, characterized by mandibular
dentoalveolar retrusion and a prominent chin, underwent archwise alveolar
distraction in the anterior mandible. Lateral cephalometric radiographs were
obtained before distraction (T0), after 6 weeks of consolidation (T1), and after
debonding (T2). Linear and angular skeletal, dental, and soft tissue measurements
were performed. Forty-seven parameters were measured for each of the 15 subjects
on pre- and postoperative lateral cephalometric radiographs (T0, T1, and T2). The
distraction protocol was successful in all patients. Skeletally, the mandible
showed a clockwise rotation. B-point moved forward significantly (P<0.05).
Overjet decreased significantly (P<0.001). The total profile angle was
unaffected, and the improvement in the submental fold was highly significant
(P<0.001). The intraoral archwise distraction force that is applied through
brackets and archwires is sufficiently effective for alveolar advancement. This
procedure is simple and effective in the treatment of specific adult patients
with a class II division 2 malocclusion, characterized by a prominent chin and
severe mandibular dentoalveolar retrusion.
PMID- 28416097
TI - Long-term effect of presurgical nasoalveolar molding on growth of maxillary arch
in unilateral cleft lip and palate: randomized controlled trial.
AB - The objective of this study was to investigate the long-term effect of
presurgical nasoalveolar molding (PNAM) on growth of the maxillary arch through
early childhood until 6 years of age in complete unilateral cleft lip and palate
(UCLP) patients presenting for PNAM at different ages. Complete UCLP patients who
were treated at our centre were divided into two groups. The study group
underwent PNAM and was further subdivided into three subgroups (PNAM initiated
within 1 month, between 1 and 6 months, and between 6 and 12 months of age in
subgroup I, II, and III, respectively). The control group did not undergo PNAM
and was further subdivided into three subgroups. Patients were evaluated at T1
(first visit), T2 (before cheiloplasty), and T3 (at 6 years). Between T1and T2,
the intersegment distance (ISD) reduced significantly in the study group but
increased in the control group, whereas the intercanine width (ICW) in both the
study and control groups did not show significant change. Between T2 and T3, ISD
and ICW were reduced significantly in the control group due to arch collapse,
whereas in the study group, ISD reduced slightly with ICW remaining almost
similar to noncleft norms. We conclude that reduced ISD following PNAM improves
arch symmetry and stability, and thus may prevent arch collapse in the long term.
PMID- 28416099
TI - Statin use and risk of new-onset diabetes: A meta-analysis of observational
studies.
AB - BACKGROUND AND AIMS: Meta-analyses of randomized control trials investigating the
association between incident diabetes and statin use showed an increased risk of
new-onset diabetes (NOD) from 9% to 13% associated with statins. However, short
follow-up period, unpowered sample size, and lack of pre-specified diagnostic
criteria for diabetes detection could be responsible of an underestimation of
this risk. We conducted a meta-analysis of published observational studies to
evaluate the association between statins use and risk of NOD. METHODS AND
RESULTS: PubMed, EMBASE and MEDLINE databases were searched from inception to
June 30, 2016 for cohort and case-control studies with risk of NOD in users vs
nonusers, on >=1000 subjects followed-up for >=1 year. Two review authors
assessed study eligibility and risk of bias and undertook data extraction
independently. Pooled estimates were calculated by a random-effects model and
between-study heterogeneity was tested and measured by I2 index. Furthermore,
stratified analyses and the evaluation of publication bias were performed.
Finally, the meta-analysis included 20 studies, 18 cohort and 2 case-control
studies. Overall, NOD risk was higher in statin users than nonusers (RR 1.44; 95%
CI 1.31-1.58). High between-study heterogeneity (I2 = 97%) was found. Estimates
for all single statins showed a class effect, from rosuvastatin (RR 1.61; 1.30
1.98) to simvastatin (RR 1.38; 1.19-1.61). CONCLUSIONS: The present meta-analysis
confirms and reinforces the evidence of a diabetogenic effect by statins
utilization. These observations confirm the need of a rigorous monitoring of
patients taking statins, in particular pre-diabetic patients or patients
presenting with established risk factors for diabetes.
PMID- 28416100
TI - Synthesis and biological evaluation of largazole zinc-binding group analogs.
AB - Histone acetylation is an extensively investigated post-translational
modification that plays an important role as an epigenetic regulator. It is
controlled by histone acetyl transferases (HATs) and histone deacetylases
(HDACs). The overexpression of HDACs and consequent hypoacetylation of histones
have been observed in a variety of different diseases, leading to a recent focus
of HDACs as attractive drug targets. The natural product largazole is one of the
most potent natural HDAC inhibitors discovered so far and a number of largazole
analogs have been prepared to define structural requirements for its HDAC
inhibitory activity. However, previous structure-activity relationship studies
have heavily investigated the macrocycle region of largazole, while there have
been only limited efforts to probe the effect of various zinc-binding groups
(ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with
various ZBGs and evaluated their HDAC inhibition and cytotoxicity. While none of
the analogs tested were as potent or selective as largazole, the Zn2+-binding
affinity of each ZBG correlated with HDAC inhibition and cytotoxicity. We expect
that our findings will aid in building a deeper understanding of the role of ZBGs
in HDAC inhibition as well as provide an important basis for the future
development of new largazole analogs with non-thiol ZBGs as novel therapeutics
for cancer.
PMID- 28416101
TI - N-Substituted and ring opened saccharin derivatives selectively inhibit
transmembrane, tumor-associated carbonic anhydrases IX and XII.
AB - A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl
moieties, as well as some ring opened derivatives were prepared and investigated
as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The
widespread cytosolic isoforms CA I and II were not inhibited by these
sulfonamides whereas transmembrane, tumor-associated ones were effectively
inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA
XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides
is unknown for the moment, the good efficacy and especially selectivity for the
inhibition of the tumor-associated over the cytosolic, widespread isoforms, make
these derivatives of considerable interest as enzyme inhibitors with various
pharmacologic applications.
PMID- 28416102
TI - Synthesis, biochemical evaluation, and molecular modeling studies of aryl and
arylalkyl di-n-butyl phosphates, effective butyrylcholinesterase inhibitors.
AB - A series of dialkyl aryl phosphates and dialkyl arylalkyl phosphates were
synthesized. Their inhibitory activities were evaluated against
acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The di-n-butyl
phosphate series consistently displayed selective inhibition of BChE over AChE.
The most potent inhibitors of butyrylcholinesterase were di-n-butyl-3,5
dimethylphenyl phosphate (4b) [KI=1.0+/-0.4MUM] and di-n-butyl 2-naphthyl
phosphate (5b) [KI=1.9+/-0.4MUM]. Molecular modeling was used to uncover three
subsites within the active site gorge that accommodate the three substituents
attached to the phosphate group. Phosphates 4b and 5b were found to bind to these
three subsites in analogous fashion with the aromatic groups in both analogs
being accommodated by the "lower region," while the lone pairs on the PO oxygen
atoms were oriented towards the oxyanion hole. In contrast, di-n-butyl-3,4
dimethylphenyl phosphate (4a) [KI=9+/-1MUM], an isomer of 4b, was found to orient
its aromatic group in the "upper left region" subsite as placement of this group
in the "lower region" resulted in significant steric hindrance by a ridge-like
region in this subsite. Future studies will be designed to exploit these features
in an effort to develop inhibitors of higher inhibitory strength against
butyrylcholinesterase.
PMID- 28416098
TI - Ideal cardiovascular health and inflammation in European adolescents: The HELENA
study.
AB - BACKGROUND AND AIMS: Inflammation plays a key role in atherosclerosis and this
process seems to appear in childhood. The ideal cardiovascular health index
(ICHI) has been inversely related to atherosclerotic plaque in adults. However,
evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to
assess the association between ICHI and inflammation in European adolescents.
METHODS AND RESULTS: As many as 543 adolescents (251 boys and 292 girls) from the
Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross
sectional multi-center study including 9 European countries, were measured. C
reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell
counts were used to compute an inflammatory score. Multilevel linear models and
multilevel logistic regression were used to assess the association between ICHI
and inflammation controlling by covariates. Higher ICHI was associated with a
lower inflammatory score, as well as with several individual components, both in
boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal
components of the ICHI had significantly lower inflammatory score and lower
levels of the study biomarkers, except CRP. Finally, the multilevel logistic
regression showed that for every unit increase in the ICHI, the probability of
having an inflammatory profile decreased by 28.1% in girls. CONCLUSION: Results
from this study suggest that a better ICHI is associated with a lower
inflammatory profile already in adolescence. Improving these health behaviors,
and health factors included in the ICHI, could play an important role in CVD
prevention.
PMID- 28416103
TI - A new "twist" on right heart failure with left ventricular assist systems.
AB - Despite significant efforts to predict and prevent right heart failure, it
remains a leading cause of morbidity and mortality after implantation of left
ventricular assist systems (LVAS). In this Perspective, we review the
underappreciated anatomic and physiologic principles that govern the relationship
between left and right heart function and contribute to this phenomenon. This
includes the importance of considering the right ventricle (RV) and pulmonary
arterial circuit as a coupled system; the contribution of the left ventricle (LV)
to RV contractile function and the potential negative impact of acutely unloading
the LV; the influence of the pericardium and ventricular twist on septal
function; the role of RV deformation in reduced mechanical efficiency after
device placement; and the potential of ongoing stressors of an elevated right
sided preload. We believe an appreciation of these complex issues is required to
fully understand the expression of the unique phenotypes of right heart failure
after LVAS implantation and for developing better prognostic and therapeutic
strategies.
PMID- 28416104
TI - Multilocular cystic renal cell carcinoma: pathological t staging makes no
difference to favorable outcomes and should be reclassified. Bhatt JR, Jewett MA,
Richard PO, Kawaguchi S, Timilshina N, Evans A, Alibhai S, Finelli A.J Urol.
November 2016;196(5):1350-1355.
AB - OBJECTIVE: We evaluated survival outcomes of cystic/multilocular cystic renal
cell carcinomas in a long-term population-based study based on size and
pathological tumor stage. MATERIALS AND METHODS: We, retrospectively, reviewed a
provincial cancer registry of all histologically proven cases of multilocular
cystic renal cancers treated surgically between 1995 and 2008. All cases of
cystic necrosis were excluded from study. Primary end points were overall- and
cancer-specific survival estimated using Kaplan-Meier curves. Cox proportional
hazards models of univariable and multivariable analyses were used to assess for
factors associated with survival. RESULTS: Of 172 cases of cystic renal cancers
168 with complete data were analyzed, of which 98% were multilocular cystic.
Median patient age at treatment was 55 years and 58% of the patients were male.
More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most
cases were low Fuhrman grade (1-2). At a median follow-up of 9.75-years overall-
and cancer-specific survival was 82.1% and 100%, respectively. No difference was
noted in higher pathological T stage, size, or grade. Limitations inherent in
population-based studies include under ascertainment of cause of death, lack of
data on histologically benign cysts that are treated surgically and a lack of
central pathology review. CONCLUSIONS: Multilocular cystic renal cell carcinoma
has an excellent prognosis, which remains unchanged regardless of tumor size or
pathological T stage. This suggests a strong case for nephron and adrenal sparing
surgery when indicated, and nonsurgical management when feasible. As
postoperative follow-up protocols are dictated by staging, we propose that for
this entity pathological T staging should be abandoned or reassigned as pT1c to
guide clinicians.
PMID- 28416105
TI - Do clear cell papillary renal cell carcinomas have malignant potential? Diolombi
ML, Cheng L, Argani P, Epstein JI.Am J Surg Pathol. December 2015;39(12):1621
1634.
AB - There have been no recurrences or metastases of clear cell papillary renal cell
carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language
literature. We identified all our cases of CCPRCC (1990-2013), reviewing all
cases that preceded the formal designation of the entity. Immunohistochemical
stains were performed on 32 cases during their initial workup. In addition,
stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one
with atypical follow-up and the other with a more compact morphology, although
not performed initially. An extended panel with AMACR, CD10, and renal cell
carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in
situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case
and on another clinically presumed metastatic tumor. In classic cases,
immunohistochemical staining was not performed. Fifty-eight patients (31 women;
27 men) with follow-up data were included in our study; 39 cases were from our
consult service. The patients' ages ranged from 36 to 83 years. Thirty-five
patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of
which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1
disease (size range: 0.2-8cm), 2 patients presented with pT2 disease (8.5 and
10.3cm), 1 patient presented with pT3 disease (6.5cm sarcomatoid RCC focally
extending out of the kidney), and pathologic stage was unavailable in 2 cases.
Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2
cryoablations, and 1 cyst ablation. The resection margins were negative in all
but one case, with this case disease free after a 26-month period. Two patients
had intraoperative tumor disruption and were disease free at 9 and 34 months.
Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC).
Mean follow-up time was 21 months (range: 1-175 months), with all but 3 patients
having no evidence of disease. One patient was presumed to have contralateral
disease on the basis of imaging findings and is alive and well 37 months after
multiple partial nephrectomies. Metastatic disease to the lung was clinically
presumed in 1 patient in whom a higher-grade lesion may have been missed during
sampling of the predominantly cystic pT1b tumor and tissue confirmation of the
metastases was not obtained. Another case presented with multiple skeletal and
pulmonary metastases 8 months after resection of pT3 sarcomatoid CCPRCC. The
patient with the sarcomatoid RCC died of multifocal skeletal and pulmonary
metastatic disease 13 months after resection of the renal tumor. Our study, the
largest to date with follow-up, along with others, suggests that pure CCPRCC is
an indolent tumor and should be renamed "clear cell papillary neoplasm of low
malignant potential" to reflect their biology.
PMID- 28416106
TI - Categorizing renal oncocytic neoplasms on core needle biopsy: a morphologic and
immunophenotypic study of 144 cases with clinical follow-up. Alderman MA,
Daignault S, Wolf JS Jr, Palapattu GS, Weizer AZ, Hafez KS, Kunju LP, Wu AJ. Hum
Pathol.September 2016;55:1-10.
AB - There is limited literature on renal oncocytic neoplasms diagnosed on core
biopsy. All renal oncocytic neoplasm core biopsies from 2006 to 2013 were,
retrospectively, reviewed. Morphologic features and an immunohistochemical panel
of CK7, c-KIT, and S100A1 were assessed. Concordance with resection diagnosis,
statistical analysis including a random forest classification, and follow-up were
recorded. The postimmunohistochemical diagnoses of 144 renal oncocytic core
biopsies were favor oncocytoma (67%), favor renal cell carcinoma (RCC) (12%), and
cannot exclude RCC (21%). Diagnosis was revised following immunohistochemistry in
7% of cases. The most common features for oncocytoma (excluding dense granular
cytoplasm) were nested architecture, edematous stroma, binucleation and tubular
architecture; the most common features for favor RCC were sheet-like
architecture, nuclear pleomorphism, papillary architecture, and prominent cell
borders. High nuclear grade, necrosis, extensive papillary architecture,
raisinoid nuclei, and frequent mitoses were not seen in oncocytomas. Comparing
the pathologist and random forest classification, the overall out-of-bag estimate
of classification error dropped from 23% to 13% when favor RCC and cannot exclude
RCC was combined into 1 category. Resection was performed in 19% (28 cases) with
a 94% concordance (100% of favor RCC biopsies and 90% of cannot exclude RCC
biopsies confirmed as RCC; 83% of favor oncocytomas confirmed); ablation in 23%;
and surveillance in 46%. Follow-up was available in 92% (median follow-up, 33
months) with no adverse outcomes. Renal oncocytic neoplasms comprise a
significant subset (16%) of all core biopsies, and the majority (78%) can be
classified as favor oncocytoma or favor RCC.
PMID- 28416107
TI - Characteristics of the peritumoral pseudocapsule vary predictably with histologic
subtype of T1 renal neoplasms. Jacob JM, Williamson SR, Gondim DD, Leese JA,
Terry C, Grignon DJ, Boris RS.Urology. November 2015;86(5):956-961.
AB - OBJECTIVE: To determine characteristics of the peritumoral pseudocapsule (PC)
between renal tumor subtypes. METHODS: The peritumoral PCs of 160 pT1 renal
tumors were examined, including 60 clear cell renal cell carcinomas (RCCs), 50
papillary RCCs, 25 chromophobe RCCs, and 25 oncocytoma. Pathologic features
(presence or absence of PC, mean thickness, continuity, and invasion by tumor)
were analyzed. PC thickness was measured using an ocular micrometer to the
nearest 1/10mm. RESULTS: A complete PC was found in 77% of clear cell tumors, 74%
of papillary, 28% of chromophobe, and 4% of oncocytomas. Tumor PC was present but
incomplete in 18% of clear cell, 18% of papillary, 44% of chromophobe, and 56% of
oncocytoma. The PC was entirely absent in no clear cell tumors, 6% of papillary,
28% of chromophobe, and 40% of oncocytoma. Mean PC thickness and presence of
invasion beyond the PC differed significantly by tumor subtype. Clear cell RCC
possessed the thickest PC showing invasion through the capsule in 8% of tumors
compared to 30% of papillary tumors. Complete PC invasion was not seen in
chromophobe RCC or renal oncocytoma. Oncocytoma and chromophobe RCC
characteristically exhibited an incomplete or absent PC. CONCLUSIONS: The
characteristics of peritumoral PC vary predictably with histologic subtype of
renal neoplasms. Clear cell RCC shows the most consistent PC, with a lower rate
of invasion beyond it compared to papillary RCC. Chromophobe and oncocytoma
characteristically have an incomplete or absent PC.
PMID- 28416108
TI - Tumor necrosis adds prognostically significant information to grade in clear cell
renal cell carcinoma: A study of 842 consecutive cases from a single institution.
Khor LY, Dhakal HP, Jia X, Reynolds JP, McKenney JK, Rini BI, Magi-Galluzzi C,
Przybycin CG.Am J Surg Pathol. September 2016;40(9):1224-1231.
AB - Tumor necrosis has been shown to be an independent predictor of adverse outcome
in renal cell carcinoma. A modification of the International Society of
Urological Pathology (ISUP) grading system for renal cell carcinomas has recently
been proposed, which incorporates the presence of tumor necrosis into grade. The
investigators proposing this system found that necrosis added significant
prognostic information to ISUP grade. We attempted to describe our experience
with the effect of tumor necrosis in relationship to nuclear grade by reviewing
the slides from a large consecutive series of localized clear cell renal cell
carcinomas from our institution and obtaining long-term clinical follow-up
information (overall survival). Of the 842 clear cell renal cell carcinomas
reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and
140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. A
total of 547 (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%)
were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2
months (range: 0.12-273.6), and 310 (36.8%) patients died. On univariable
analysis, there was no significant difference in outcome for tumors of ISUP
grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade
4 and necrosis were significant predictors of overall survival on multivariable
analysis. When the recently proposed modified grading system incorporating tumor
necrosis was applied to our data, there was no significant difference in overall
survival between patients with modified grade 1 tumors and those with modified
grade 2 tumors (P = 0.31); however, there was a statistically significant
difference between patients with modified grade 1 or 2 tumors and those with
modified grade 3 tumors (P = 0.04), and a substantial difference in outcome
between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a
recursive partitioning approach was applied to our data, patients of a given ISUP
grade could be further prognostically separated according to the presence or
absence of necrosis and could be divided into 3 statistically significant
prognostic groups: (1) non-necrotic ISUP grade 1 to 3 tumors, (2) ISUP grade 1 to
3 tumors with necrosis and ISUP grade 4 tumors with<10% necrosis, and (3) ISUP
grade 4 tumors with>10% necrosis. In conclusion, our study shows that tumor
necrosis adds additional prognostic information to ISUP grade and that
quantification of necrosis can further stratify patients with ISUP grade 4
tumors.
PMID- 28416109
TI - Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy
for High Risk Renal Tumors. Shah PH, Moreira DM, Okhunov Z, Patel VR, Chopra S,
Razmaria AA, Alom M, George AK, Yaskiv O, Schwartz MJ, Desai M, Vira MA,
Richstone L, Landman J, Shalhav AL, Gill I, Kavoussi LR. J Urol. 2016
Aug;196(2):327-34.
AB - PURPOSE: The clinical significance of a positive surgical margin after partial
nephrectomy remains controversial. The association between positive margin and
risk of disease recurrence in patients with clinically localized renal neoplasms
undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A
retrospective multi-institutional review of 1,240 patients undergoing partial
nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013
was performed. Recurrence-free survival was estimated using the Kaplan-Meier
method and evaluated as a function of positive surgical margin with the log rank
test and Cox models adjusting for tumor size, grade, histology, pathological
stage, focality and laterality. The relationship between positive margin and risk
of relapse was evaluated independently for pathological high risk (pT2-3a or
Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups.
RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients.
Recurrence developed in 69 (5.6%) patients during a median followup of 33 months,
including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III
IV). A positive margin was associated with an increased risk of relapse on
multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of
recurrence. In a stratified analysis based on pathological features, a positive
surgical margin was significantly associated with a higher risk of recurrence in
cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low
risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins
after partial nephrectomy increase the risk of disease recurrence, primarily in
patients with adverse pathological features.
PMID- 28416110
TI - Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance.
AB - The macrolides are a class of antibiotic, characterized by a large macrocyclic
lactone ring that can be inactivated by macrolide phosphotransferase enzymes. We
present structures for MPH(2')-I and MPH(2')-II in the apo state, and in complex
with GTP analogs and six different macrolides. These represent the first
structures from the two main classes of macrolide phosphotransferases. The
structures show that the enzymes are related to the aminoglycoside
phosphotransferases, but are distinguished from them by the presence of a large
interdomain linker that contributes to an expanded antibiotic binding pocket.
This pocket is largely hydrophobic, with a negatively charged patch located at a
conserved aspartate residue, rationalizing the broad-spectrum resistance
conferred by the enzymes. Complementary mutation studies provide insights into
factors governing substrate specificity. A comparison with macrolides bound to
their natural target, the 50S ribosome, suggests avenues for next-generation
antibiotic development.
PMID- 28416111
TI - Structural Analysis Reveals Features of Ribosome Assembly Factor Nsa1/WDR74
Important for Localization and Interaction with Rix7/NVL2.
AB - Ribosome assembly is a complex process that requires hundreds of essential
assembly factors, including Rix7 (NVL2 in mammals) and Nsa1 (WDR74 in mammals).
Rix7 is a type II double ring, AAA-ATPase, which is closely related to the well
known Cdc48/p97. Previous studies in Saccharomyces cerevisiae suggest that Rix7
mediates the release of Nsa1 from nucleolar pre-60S particles; however, the
underlying mechanisms of this release are unknown. Through multiple structural
analyses we show that S. cerevisiae Nsa1 is composed of an N-terminal seven
bladed WD40 domain followed by a lysine-rich C terminus that extends away from
the WD40 domain and is required for nucleolar localization. Co
immunoprecipitation assays with the mammalian homologs identified a well
conserved interface within WDR74 that is important for its association with NVL2.
We further show that WDR74 associates with the D1 AAA domain of NVL2, which
represents a novel mode of binding of a substrate with a type II AAA-ATPase.
PMID- 28416113
TI - Early Evolution of Specialized Termitophily in Cretaceous Rove Beetles.
AB - Termitophiles, symbionts that live in termite nests, include a wide range of
morphologically and behaviorally specialized organisms. Complex adaptive
mechanisms permit these animals to integrate into societies and to exploit their
controlled physical conditions and plentiful resources, as well as to garner
protection inside termite nests. An understanding of the early evolution of
termitophily is challenging owing to a scarcity of fossil termitophiles, with all
known reliable records occurring from the Miocene (approximately 19 million years
ago [mya]) [1-6], and an equivocal termitophile belonging to the largely free
living Mesoporini from the mid-Cretaceous [7]. Here we report the oldest,
morphologically specialized, and obligate termitophiles from mid-Cretaceous
Burmese amber (99 mya). Cretotrichopsenius burmiticus gen. et sp. nov. belongs to
Trichopseniini, a group of distinctive termitophilous aleocharine rove beetles,
all of which possess specialized swollen or horseshoe-crab-shaped body plans.
Cretotrichopsenius display the protective horseshoe-crab-shaped body form typical
of many modern termitophiles, with concealed head and antennae and strong
posteriorly directed abdominal setae. Cretotrichopsenius represent the earliest
definitive termitophiles, shedding light on host associations in the early
evolution of termite societies. The fossil reveals that ancient termite societies
were quickly invaded by beetles and by multiple independent lineages of social
parasites over the subsequent eons.
PMID- 28416112
TI - Flexibility and Design: Conformational Heterogeneity along the Evolutionary
Trajectory of a Redesigned Ubiquitin.
AB - Although protein design has been used to introduce new functions, designed
variants generally only function as well as natural proteins after rounds of
laboratory evolution. One possibility for this pattern is that designed mutants
frequently sample nonfunctional conformations. To test this idea, we exploited
advances in multiconformer modeling of room-temperature X-ray data collection on
redesigned ubiquitin variants selected for increasing binding affinity to the
deubiquitinase USP7. Initial core mutations disrupt natural packing and lead to
increased flexibility. Additional, experimentally selected mutations quenched
conformational heterogeneity through new stabilizing interactions. Stabilizing
interactions, such as cation-pi stacking and ordered waters, which are not
included in standard protein design energy functions, can create specific
interactions that have long-range effects on flexibility across the protein. Our
results suggest that increasing flexibility may be a useful strategy to escape
local minima during initial directed evolution and protein design steps when
creating new functions.
PMID- 28416114
TI - Invariance of Initiation Mass and Predictability of Cell Size in Escherichia
coli.
AB - It is generally assumed that the allocation and synthesis of total cellular
resources in microorganisms are uniquely determined by the growth conditions.
Adaptation to a new physiological state leads to a change in cell size via
reallocation of cellular resources. However, it has not been understood how cell
size is coordinated with biosynthesis and robustly adapts to physiological
states. We show that cell size in Escherichia coli can be predicted for any
steady-state condition by projecting all biosynthesis into three measurable
variables representing replication initiation, replication-division cycle, and
the global biosynthesis rate. These variables can be decoupled by selectively
controlling their respective core biosynthesis using CRISPR interference and
antibiotics, verifying our predictions that different physiological states can
result in the same cell size. We performed extensive growth inhibition
experiments, and we discovered that cell size at replication initiation per
origin, namely the initiation mass or unit cell, is remarkably invariant under
perturbations targeting transcription, translation, ribosome content, replication
kinetics, fatty acid and cell wall synthesis, cell division, and cell shape.
Based on this invariance and balanced resource allocation, we explain why the
total cell size is the sum of all unit cells. These results provide an
overarching framework with quantitative predictive power over cell size in
bacteria.
PMID- 28416115
TI - In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals
Differences between Functional Classes of Motoneurons in Zebrafish.
AB - The interplay between binding and unbinding of synaptic receptor proteins at
synapses plays an important role in determining receptor concentration and
synaptic strength, with known links between changes in binding kinetics and
synaptic plasticity. The regulation of such kinetics may subserve the specific
functional requirements of neurons in intact circuits. However, the majority of
studies of synaptic turnover kinetics have been performed in cultured neurons
outside the context of normal circuits, and synaptic receptor turnover has not
been measured at individual synaptic sites in vivo. We quantified the
distribution of glycinergic receptor dynamics using fluorescence recovery after
photoconversion of synapses in intact zebrafish and correlated recovery kinetics
to synaptic volume in two functionally distinct classes of cells: primary and
secondary motoneurons. The rate of fluorescence recovery after photoconversion
decreased with synaptic volume in both types of motoneurons, with larger synapses
having slower recovery. Primary motoneurons had both larger synapses and
associated slower recovery times than secondary motoneurons. Our results suggest
that synaptic kinetics are regulated in concert with synaptic sizes and reflect
the functional role played by neurons within their circuit.
PMID- 28416116
TI - Activation of a Plant NLR Complex through Heteromeric Association with an
Autoimmune Risk Variant of Another NLR.
AB - When independently evolved immune receptor variants meet in hybrid plants, they
can activate immune signaling in the absence of non-self recognition. Such
autoimmune risk alleles have recurrently evolved at the DANGEROUS MIX2 (DM2)
nucleotide-binding domain and leucine-rich repeat (NLR)-encoding locus in A.
thaliana. One of these activates signaling in the presence of a particular
variant encoded at another NLR locus, DM1. We show that the risk variants of DM1
and DM2d NLRs signal through the same pathway that is activated when plant NLRs
recognize non-self elicitors. This requires the P loops of each protein and
Toll/interleukin-1 receptor (TIR)-domain-mediated heteromeric association of DM1
and DM2d. DM1 and DM2d each resides in a multimeric complex in the absence of
signaling, with the DM1 complex shifting to higher molecular weight when
heteromerizing DM2 variants are present. The activation of the DM1 complex
appears to be sensitive to the conformation of the heteromerizing DM2 variant.
Autoimmunity triggered by interaction of this NLR pair thus suggests that
activity of heteromeric NLR signaling complexes depends on the sum of activation
potentials of partner NLRs.
PMID- 28416117
TI - Rapid Spatial Learning Controls Instinctive Defensive Behavior in Mice.
AB - Instinctive defensive behaviors are essential for animal survival. Across the
animal kingdom, there are sensory stimuli that innately represent threat and
trigger stereotyped behaviors such as escape or freezing [1-4]. While innate
behaviors are considered to be hard-wired stimulus-responses [5], they act within
dynamic environments, and factors such as the properties of the threat [6-9] and
its perceived intensity [1, 10, 11], access to food sources [12-14], and
expectations from past experience [15, 16] have been shown to influence defensive
behaviors, suggesting that their expression can be modulated. However, despite
recent work [2, 4, 17-21], little is known about how flexible mouse innate
defensive behaviors are and how quickly they can be modified by experience. To
address this, we have investigated the dependence of escape behavior on learned
knowledge about the spatial environment and how the behavior is updated when the
environment changes acutely. Using behavioral assays with innately threatening
visual and auditory stimuli, we show that the primary goal of escape in mice is
to reach a previously memorized shelter location. Memory of the escape target can
be formed in a single shelter visit lasting less than 20 s, and changes in the
spatial environment lead to a rapid update of the defensive action, including
changing the defensive strategy from escape to freezing. Our results show that
although there are innate links between specific sensory features and defensive
behavior, instinctive defensive actions are surprisingly flexible and can be
rapidly updated by experience to adapt to changing spatial environments.
PMID- 28416118
TI - A Magnetic Map Leads Juvenile European Eels to the Gulf Stream.
AB - Migration allows animals to track the environmental conditions that maximize
growth, survival, and reproduction [1-3]. Improved understanding of the
mechanisms underlying migrations allows for improved management of species and
ecosystems [1-4]. For centuries, the catadromous European eel (Anguilla anguilla)
has provided one of Europe's most important fisheries and has sparked
considerable scientific inquiry, most recently owing to the dramatic collapse of
juvenile recruitment [5]. Larval eels are transported by ocean currents
associated with the Gulf Stream System from Sargasso Sea breeding grounds to
coastal and freshwater habitats from North Africa to Scandinavia [6, 7]. After a
decade or more, maturing adults migrate back to the Sargasso Sea, spawn, and die
[8]. However, the migratory mechanisms that bring juvenile eels to Europe and
return adults to the Sargasso Sea remain equivocal [9, 10]. Here, we used a
"magnetic displacement" experiment [11, 12] to show that the orientation of
juvenile eels varies in response to subtle differences in magnetic field
intensity and inclination angle along their marine migration route. Simulations
using an ocean circulation model revealed that even weakly swimming in the
experimentally observed directions at the locations corresponding to the magnetic
displacements would increase entrainment of juvenile eels into the Gulf Stream
System. These findings provide new insight into the migration ecology and
recruitment dynamics of eels and suggest that an adaptive magnetic map, tuned to
large-scale features of ocean circulation, facilitates the vast oceanic
migrations of the Anguilla genus [7, 13, 14].
PMID- 28416119
TI - The Head-Direction Signal Plays a Functional Role as a Neural Compass during
Navigation.
AB - The rat limbic system contains head direction (HD) cells that fire according to
heading in the horizontal plane, and these cells are thought to provide animals
with an internal compass. Previous work has found that HD cell tuning correlates
with behavior on navigational tasks, but a direct, causal link between HD cells
and navigation has not been demonstrated. Here, we show that pathway-specific
optogenetic inhibition of the nucleus prepositus caused HD cells to become
directionally unstable under dark conditions without affecting the animals'
locomotion. Then, using the same technique, we found that this decoupling of the
HD signal in the absence of visual cues caused the animals to make directional
homing errors and that the magnitude and direction of these errors were in a
range that corresponded to the degree of instability observed in the HD signal.
These results provide evidence that the HD signal plays a causal role as a neural
compass in navigation.
PMID- 28416120
TI - Diabetes Complications Severity Index (DCSI)-Update and ICD-10 translation.
AB - AIMS: The Diabetes Complications Severity Index (DCSI) converts diagnostic codes
and laboratory results into a 14-level metric quantifying the long-term effects
of diabetes on seven body systems. Adoption of the International Classification
of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) necessitates
translation from ICD-9-CM and creates refinement opportunities. METHODS: ICD-9
codes for secondary and primary diabetes plus all five ICD-10 diabetes categories
were incorporated into an updated tool. Additional modifications were made to
improve the accuracy of severity assignments. SUBJECTS: The tools were tested in
a Medicare Advantage population. RESULTS: In the type 2 subpopulation, prevalence
steadily declined with increasing score according to the updated DCSI tool,
whereas the original tool resulted in an aberrant local prevalence peak at DCSI =
2. In the type 1 subpopulation, score prevalence was greater in type 1 versus
type 2 subpopulations (3 versus 0) according to both instruments. Both
instruments predicted current-year inpatient admissions risk and near-future
mortality, using either purely ICD-9 data or a mix of ICD-9 and ICD-10 data.
DISCUSSION: While the performance of the tool with purely ICD-10 data has yet to
be evaluated, this updated tool makes assessment of diabetes patient severity and
complications possible in the interim.
PMID- 28416121
TI - Silent coronary heart disease in patients with type 2 diabetes: application of a
screening approach in a follow-up study.
AB - AIMS: The cost-effectiveness of screening for silent coronary heart disease (CHD)
in type 2 diabetes (DM2) is still debated. METHODS: We applied a diagnostic
algorithm for silent CHD detection, in a cohort of 102 asymptomatic DM2 subjects
(57+/-7years), attending 5 Italian outpatient clinics, to verify its predictive
value. The risk of silent CHD was calculated considering classical risk factors,
and presence of microangiopathy/macroangiopathy. Patients were divided in 3
groups, i.e. group 1: normal ECG and low silent CHD risk; group 2: abnormal ECG,
irrespective of silent CHD risk; group 3: high silent CHD risk, irrespective of
ECG. To group 2 and 3, a functional test was recommended and performed in 78% of
patients. RESULTS: Silent CHD prevalence was similar in group 2 and 3 (25 vs. 17%
respectively; p=0.495). However, evaluating the entire cohort, a significant
higher prevalence of silent CHD was observed in subjects with abnormal vs. normal
ECG (23 vs. 4%; P=0.004), but not in subjects with high vs. low pre-test silent
CHD risk (14 vs. 9%; p=0.472). CONCLUSIONS: An abnormal ECG was a strong,
independent predictor of silent CHD (OR 8.9; CI 1.27-62.5; p=0.028) in DM2.
Therefore, a functional stress testing should be considered in DM2 patients with
ECG abnormalities.
PMID- 28416123
TI - Immune Checkpoint Inhibitors for Patients With Advanced Non-Small-Cell Lung
Cancer: A Systematic Review.
AB - Second-line treatment options are limited for patients with advanced non-small
cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents
docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors
are a new class of treatment that have shown durable overall radiologic response
rates and have been well tolerated. The objective of this systematic review was
to investigate the efficacy of immune checkpoint inhibitors compared with other
chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were
searched for randomized controlled trials comparing treatment with immune
checkpoint inhibitors against treatment with chemotherapy in patients with stage
IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were
included. A significant overall survival benefit of second-line nivolumab
(nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77;
P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line
atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line
pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive
tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008;
pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line
pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy
was found. The adverse effects were mainly higher in the chemotherapy arms. For
patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival
outweighed the harms and supported the use of first-line pembrolizumab (in
patients with >= 50% PD-L1-positive tumors) or second-line nivolumab,
atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors).
PMID- 28416122
TI - Patients with a resected pancreatic mucinous cystic neoplasm have a better
prognosis than patients with an intraductal papillary mucinous neoplasm: A large
single institution series.
AB - BACKGROUND/OBJECTIVES: Mucinous cystic neoplasms (MCNs) are rare pancreas tumors
distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the
presence of ovarian-type stroma. Historical outcomes for MCNs vary due to
previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This
study seeks to characterize and clarify the clinical features and long-term
outcomes of MCNs versus IPMNs in the largest single-institution series of
pathology-confirmed MCNs to date. METHODS: We compared 142 MCNs and 746 IPMNs
resected at a single institution. MCNs were reviewed for confirmation of ovarian
type stroma and reclassified according to current WHO guidelines. RESULTS: MCNs
presented almost exclusively in middle-aged women (median 47.5 years, 96.5%
female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas
(92.1%). IPMNs were distributed equally by sex in an older population (median
69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared
with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1%
vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs
(9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs.
Patients with an MCN-associated invasive carcinoma had a much better prognosis
than did patients with an IPMN-associated invasive carcinoma with 10-year disease
specific survival of 79.6% versus 27.2%, respectively. CONCLUSION: MCNs have a
stereotypical clinical profile that is readily distinguishable from IPMNs based
on demographic features, imaging, and pathology. Most MCNs are noninvasive and
curable with surgical resection. Prognosis remains excellent even for invasive
disease with 10-year survival approaching 80% following resection.
PMID- 28416124
TI - Assessment of the External Validity of the National Comprehensive Cancer Network
and European Society for Medical Oncology Guidelines for Non-Small-Cell Lung
Cancer in a Population of Patients Aged 80 Years and Older.
AB - Non-small-cell lung cancer (NSCLC) is a disease of the elderly, who are under
represented in clinical trials. This challenges the external validity of the
evidence base for its management and of current guidelines, that we evaluated in
a population of older patients. We retrieved randomized clinical trials (RCTs)
supporting the guidelines and identified 18 relevant topics. We matched a cohort
of NSCLC patients aged older than 80 years from the Moffitt Cancer Center
database with the studies' eligibility criteria to check their qualification for
at least 2 studies. Eligibility > 60% was rated full validity, 30% to 60% partial
validity, and < 30% limited validity. We obtained data from 760 elderly patients
in stage-adjusted groups and collected 244 RCTs from the National Comprehensive
Cancer Network (NCCN) and 148 from the European Society for Medical Oncology
(ESMO) guidelines. External validity was deemed insufficient for neoadjuvant
chemotherapy in stage III disease (27.37% and 25.26% of patients eligible for
NCCN and ESMO guidelines, respectively) and use of bevacizumab (13.86% and 16.27%
of patients eligible). For ESMO guidelines, it was inadequate regarding double
agent chemotherapy (25.90% of patients eligible), its duration (24.10%) and
therapy for Eastern Cooperative Oncology Group performance status 2 patients
(17.74%). For NCCN guidelines external validity was lacking for neoadjuvant
chemoradiotherapy in stage IIIA disease (25.86% of patients eligible). Our
analysis highlighted the effect of RCT eligibility criteria on guidelines'
external validity in elderly patients. Eligibility criteria should be carefully
considered in trial design and more studies that do not exclude elderly patients
should be included in guidelines.
PMID- 28416125
TI - Efficacy of pretreating oil palm fronds with an acid-base mixture catalyst.
AB - Oil palm fronds are abundant but recalcitrant to chemical pretreatment. Herein,
an acid-base mixture was applied as a catalyst to efficiently pretreat oil palm
fronds. Optimized conditions for the pretreatment were a 0.1M acidic acid-base
mixture and 3min ramping to 190 degrees C and 12min holding. The oil palm fronds
pretreated and washed with the acid-base mixture exhibited an enzymatic
digestibility of 85% by 15 FPU Accellerase 1000/g glucan after 72h hydrolysis,
which was significantly higher than the enzymatic digestibilities obtained by
acid or alkali pretreatment alone. This could be attributed to the synergistic
actions of the acid and base, producing an 87% glucose recovery with 100% and
40.3% removal of xylan and lignin, respectively, from the solids. Therefore, an
acid-base mixture can be a feasible catalyst to deconstruct oil palm fronds for
sugar production.
PMID- 28416126
TI - Biokinetic model-based multi-objective optimization of Dunaliella tertiolecta
cultivation using elitist non-dominated sorting genetic algorithm with
inheritance.
AB - Algal model based multi-objective optimization using elitist non-dominated
sorting genetic algorithm with inheritance was carried out for batch cultivation
of Dunaliella tertiolecta using NPK-fertilizer. Optimization problems involving
two- and three-objective functions were solved simultaneously. The objective
functions are: maximization of algae-biomass and lipid productivity with
minimization of cultivation time and cost. Time variant light intensity and
temperature including NPK-fertilizer, NaCl and NaHCO3 loadings are the important
decision variables. Algal model involving Monod/Andrews adsorption kinetics and
Droop model with internal nutrient cell quota was used for optimization studies.
Sets of non-dominated (equally good) Pareto optimal solutions were obtained for
the problems studied. It was observed that time variant optimal light intensity
and temperature trajectories, including optimum NPK fertilizer, NaCl and NaHCO3
concentration has significant influence to improve biomass and lipid productivity
under minimum cultivation time and cost. Proposed optimization studies may be
helpful to implement the control strategy in scale-up operation.
PMID- 28416127
TI - Experimental and modelling of Arthrospira platensis cultivation in open raceway
ponds.
AB - In this study, the growth of Arthrospira platensis was studied in an open raceway
pond. Furthermore, dynamic model for algae growth and CFD modelling of
hydrodynamics in open raceway pond were developed. The dynamic behaviour of the
algal system was developed by solving mass balance equations of various
components, considering light intensity and gas-liquid mass transfer. A CFD
modelling of the hydrodynamics of open raceway pond was developed by solving mass
and momentum balance equations of the liquid medium. The prediction of algae
concentration from the dynamic model was compared with the experimental data. The
hydrodynamic behaviour of the open raceway pond was compared with the literature
data for model validation. The model predictions match the experimental findings.
Furthermore, the hydrodynamic behaviour and residence time distribution in our
small raceway pond were predicted. These models can serve as a tool to assess the
pond performance criteria.
PMID- 28416128
TI - Carbamazepine responsive generalized dystonia in Fahr's disease.
PMID- 28416129
TI - Increase in Parkinson's disease-related mortality among males in Northern Italy.
AB - BACKGROUND: According to standard mortality statistics based on the underlying
cause of death (UCOD), mortality from Parkinson's disease (PD) is increasing in
most European countries. However, mortality trends are better investigated taking
into account all the diseases reported in the death certificate (multiple causes
of death approach, MCOD). METHODS: All deaths of residents in the Veneto Region
(Northern Italy) aged>=45 years with any mention of PD were extracted from 2008
to 2015. The Annual Percent Change (APC) in age-standardized mortality rates was
computed both for PD as the UCOD, and by MCOD. The association with common
chronic comorbidities and acute complications was investigated by log-binomial
regression. The frequency of the mention of PD in death certificates was
investigated through linkage with an archive of patients with a previous clinical
diagnosis of the disease. RESULTS: PD was reported in 2.1% of all deaths, rising
from 1.9% in 2008 to 2.4% in 2015. Among males, age-standardized rates increased
over time both in analyses based on the UCOD (APC +4.1%; Confidence Interval
+1.5%,+6.7%), and on MCOD (APC +2.2%; +0.2,+4.2%). Among females time trends were
not significant. Mention of PD was associated with that of dementia/Alzheimer and
acute infectious diseases. Among known PD patients, the disease was reported only
in 60.2% of death certificates. CONCLUSIONS: Mortality associated to PD is
steeply increasing among males in Northern Italy; further investigations on time
trends for PD, both through all available electronic health archives and clinical
studies, should be set as a priority for epidemiological research.
PMID- 28416130
TI - pH-Dependant fluorescence switching of an i-motif structure incorporating an
isomeric azobenzene/pyrene fluorophore.
AB - In this study, we synthesized an Azo-py phosphoramidite, featuring azobenzene and
pyrene units, as a novel fluorescent and isomeric (trans- and cis-azobenzene
units) material, which we incorporated in an i-motif DNA sequence. We then
monitored the structural dynamics and changes in fluorescence as the modified DNA
sequences transformed from single strands at pH 7 to i-motif quadruplex
structures at pH 3. After incorporating Azo-py into the 4A loop position of an i
motif sequence, dramatic changes in fluorescence occurred as the DNA structures
changed from single-strands to i-motif quadruplex structures. Interestingly, the
cis form of Azo-py induced a more stable i-motif structure than did the trans
form, as confirmed from circular dichroism spectra and melting temperature data.
The absorption and fluorescence signals of these Azo-py-incorporated i-motif
systems exhibited switchable and highly correlated signaling patterns. Such
isomeric structures based on Azo-py might find potential applications in biology,
where control over stable i-motif quadruplex structures might be performed with
switchable fluorescence signaling.
PMID- 28416131
TI - Discovery of benzophosphadiazine drug candidate IDX375: A novel hepatitis C
allosteric NS5B RdRp inhibitor.
AB - Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central
role in virus replication. NS5B has no functional equivalent in mammalian cells,
and as a consequence is an attractive target for selective inhibition. This paper
describes the discovery of a novel family of HCV NS5B non-nucleoside inhibitors
inspired by the bioisosterism between sulfonamide and phosphonamide. Systematic
structural optimization in this new series led to the identification of IDX375, a
potent non-nucleoside inhibitor that is selective for genotypes 1a and 1b. The
structure and binding domain of IDX375 were confirmed by X-ray co-crystalisation
study.
PMID- 28416133
TI - Generation of a cysteine sulfinic acid analog for incorporation in peptides using
solid phase peptide synthesis.
AB - The sulfinic acid analog of aspartic acid, cysteine sulfinic acid, introduces a
sulfur atom that perturbs the acidity and oxidation properties of aspartic acid.
Cysteine sulfinic acids are often introduced in peptides and proteins by
oxidation of cysteine, but this method is limited as all cysteine residues are
oxidized and cysteine residues are often oxidized to sulfonic acids. To provide
the foundation for the specific incorporation of cysteine sulfinic acids in
peptides and proteins, we synthesized a 9-fluorenylmethyloxycarbonyl (Fmoc)
benzothiazole sulfone analog. Oxidation conditions to generate the sulfone were
examined and oxidation of the Fmoc-protected sulfide (3) with NbC in hydrogen
peroxide provided the corresponding sulfone (4) in the highest yield and purity.
Reduction with sodium borohydride generated the cysteine sulfinic acid (5)
suggesting this approach may be an efficient method to incorporate a cysteine
sulfinic acid in biomolecules. A model tripeptide bearing a cysteine sulfinic
acid was synthesized using this approach. Future studies are aimed at using this
method to incorporate cysteine sulfinic acids in peptide hormones and proteins
for use in the study of biological function.
PMID- 28416132
TI - Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential
treatments for hypertension.
AB - We report the discovery and hit-to-lead optimization of a structurally novel
indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series
displays potent inhibition of CYP11B2, high selectivity versus related steroidal
and hepatic CYP targets, and lead-like physical and pharmacokinetic properties.
On the basis of these and other data, the indazole series was progressed to lead
optimization for further refinement.
PMID- 28416134
TI - Syntheses of benzophenone-xanthone hybrid polyketides and their antibacterial
activities.
AB - Muchimangins are benzophenone-xanthone hybrid polyketides produced by Securidaca
longepedunculata. However, their biological activities have not been fully
investigated, since they are minor constituents in this plant. To evaluate the
possibility of muchimangins as antibacterial agent candidates, five muchimangin
analogs were synthesized from 2,4,5-trimethoxydiphenyl methanol and the
corresponding xanthones, by utilizing p-toluenesulfonic acid monohydrate for the
Bronsted acid-catalysis. The antibacterial assays against Gram-positive bacteria,
Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria,
Klebsiella pneumoniae and Escherichia coli, revealed that the muchimangin analogs
(+/-)-1,3,6,8-tetrahydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone
(1), (+/-)-1,3,6-trihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone
(2), and (+/-)-1,3-dihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)
xanthone (3) showed significant activities against S. aureus, with MIC values of
10.0, 10.0, and 25.0MUM, respectively. Analogs (+/-)-1 and (+/-)-2 also exhibited
antibacterial activities against B. subtilis, with MIC values of 50.0 and
12.5MUM, respectively. Furthermore, (+)-3 enhanced the antibacterial activity
against S. aureus, with a MIC value of 10MUM.
PMID- 28416136
TI - Antipsychotics Use in Parkinson Disease: Separating Appropriate Therapies from
Treating Inappropriately.
PMID- 28416137
TI - Comment on "Preoperative asymmetry is a risk factor for reoperation in
involutional blepharoptosis".
PMID- 28416135
TI - All the "RAGE" in lung disease: The receptor for advanced glycation endproducts
(RAGE) is a major mediator of pulmonary inflammatory responses.
AB - The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory
pattern recognition receptor (PRR) that has been implicated in the pathogenesis
of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells
and was named for its ability to bind advanced glycation endproducts and promote
vascular inflammation in the vessels of patients with diabetes. Further studies
revealed that RAGE is most highly expressed in lung tissue and spurred numerous
explorations into RAGE's role in the lung. These studies have found that RAGE is
an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary
fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung
injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not
yet been targeted in the lungs of paediatric or adult clinical populations, but
the development of new ways to inhibit RAGE is setting the stage for the
emergence of novel therapeutic agents for patients suffering from these pulmonary
conditions.
PMID- 28416138
TI - Patient-centered outcomes of breast reconstruction in the setting of post
mastectomy radiotherapy: A comprehensive review of the literature.
AB - BACKGROUND: The impact of post-mastectomy radiotherapy (PMRT) on patient-centered
outcomes of breast reconstruction remains unclear. This comprehensive review aims
to consolidate the available data regarding aesthetic outcomes, patient
satisfaction, and the BREAST-Q(c) following breast reconstruction in the setting
of PMRT to facilitate the informed consent and shared decision-making process.
MATERIALS AND METHODS: A systematic search of the literature published from 2000
to 2016 in the PubMed/MEDLINE database was performed to identify all manuscripts
reporting aesthetic outcome, patient satisfaction, or BREAST-Q(c) scores of
patients undergoing PMRT and breast reconstruction. RESULTS: The initial search
identified 1604 potential titles. Ultimately, 29 manuscripts fit inclusion
criteria and were included in this review. A total of 21 studies reported
measures of aesthetic outcomes (1611 patients). Positive aesthetic outcomes
("good" or "better") widely varied in patients with prosthetic reconstruction and
ranged from 36% to 100%. In addition, positive aesthetic outcomes following
autologous reconstruction ranged from 70% to 90%. Measures of patient
satisfaction were evaluated in eight studies (722 patients). Satisfaction rates
ranged from 41% to 90% following prosthetic reconstruction and 74%-75% following
autologous reconstruction. BREAST-Q(c) findings were reported in four studies
(575 patients), all evaluating outcomes following prosthetic reconstruction. The
range of satisfaction with breasts was 48.9-57.2; satisfaction with outcome, 63.8
70.2; psychosocial well-being, 63.9-72.3; sexual well-being, 45.4-55.4; and
physical well-being, 71.7-75.1. CONCLUSIONS: Breast reconstruction in the setting
of PMRT is associated with poorer outcomes. However, the majority of studies
indicate that acceptable rates of positive aesthetic outcomes and patient
satisfaction can be achieved in the setting of PMRT.
PMID- 28416139
TI - CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond.
AB - Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide
T cells with engineered specificity. Clinical success in treating B-cell
malignancies has demonstrated the therapeutic potential of CAR-T cells against
cancer, and efforts are underway to expand the use of engineered T cells to the
treatment of diverse medical conditions, including infections and autoimmune
diseases. Here, we review current understanding of the molecular properties of
CARs, how this knowledge informs the rational design and characterization of
novel receptors, the successes and shortcomings of CAR-T cells in the clinic, and
emerging solutions for the continued improvement of CAR-T cell therapy.
PMID- 28416141
TI - Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single
Cells.
AB - The study of enhancers has been hampered by the scarcity of methods to
systematically quantify their endogenous activity. We develop Mosaic-seq to
systematically perturb enhancers and measure their endogenous activities at
single-cell resolution. Mosaic-seq uses a CRISPR barcoding system to jointly
measure a cell's transcriptome and its sgRNA modulators, thus quantifying the
effects of dCas9-KRAB-mediated enhancer repression in single cells. Applying
Mosaic-seq to 71 constituent enhancers from 15 super-enhancers, our analysis of
51,448 sgRNA-induced transcriptomes finds that only a small number of
constituents are major effectors of target gene expression. Binding of p300 and
RNAPII are key features of these constituents. We determine two key parameters of
enhancer activity in single cells: their penetrance in a population and their
contribution to expression in these cells. Through combinatorial interrogation,
we find that simultaneous repression of multiple weak constituents can alter
super-enhancer activity in a manner greatly exceeding repression of individual
constituents.
PMID- 28416142
TI - Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular
disease.
AB - Administration of drugs and other therapeutic agents has been the central
strategy of contemporary medicine for cardiovascular disease. The use of drug
delivery systems (DDS) includes micelles, liposomes, polymeric nanoparticles,
dendrimers, carbon nanotubes, and crystalline metals. Nano-DDS modify in vivo
drug kinetics, depending on (patho)physiological mechanisms such as retard
excretion, vascular permeability, and incorporation by mononuclear phagocyte
systems, which constitute the 'passive-targeting' property of nano-DDS. These
properties of nano-DDS are applicable to inflammatory diseases including
atherosclerosis. Atherosclerotic plaque destabilization and rupture account for
the majority of acute myocardial infarction, for which inflammatory monocytes and
macrophages play critical roles. In our experience, polymeric nanoparticles have
been delivered to inflammatory monocytes and macrophages in an atherosclerotic
mouse model. Nano-DDS loaded with pioglitazone reduced Ly6Chigh inflammatory
monocytes and increased Ly6Clow non-inflammatory monocytes in the peripheral
blood, and induced M2 macrophage-associated genes in the aorta. Pioglitazone
nanoparticles finally stabilized atherosclerotic plaques assessed by a decrease
in the number of buried fibrous caps in the plaque. Application of nano-DDS is a
unique and promising approach to prevent life-threatening cardiovascular events
including acute myocardial infarction by regulating inflammation in the
cardiovascular system.
PMID- 28416140
TI - Ribonucleotide Reductase Requires Subunit Switching in Hypoxia to Maintain DNA
Replication.
AB - Cells exposed to hypoxia experience replication stress but do not accumulate DNA
damage, suggesting sustained DNA replication. Ribonucleotide reductase (RNR) is
the only enzyme capable of de novo synthesis of deoxyribonucleotide triphosphates
(dNTPs). However, oxygen is an essential cofactor for mammalian RNR (RRM1/RRM2
and RRM1/RRM2B), leading us to question the source of dNTPs in hypoxia. Here, we
show that the RRM1/RRM2B enzyme is capable of retaining activity in hypoxia and
therefore is favored over RRM1/RRM2 in order to preserve ongoing replication and
avoid the accumulation of DNA damage. We found two distinct mechanisms by which
RRM2B maintains hypoxic activity and identified responsible residues in RRM2B.
The importance of RRM2B in the response to tumor hypoxia is further illustrated
by correlation of its expression with a hypoxic signature in patient samples and
its roles in tumor growth and radioresistance. Our data provide mechanistic
insight into RNR biology, highlighting RRM2B as a hypoxic-specific, anti-cancer
therapeutic target.
PMID- 28416143
TI - Changing the practice learning landscape.
AB - Engagement in real life practice has long been acknowledged as the most effective
way to learn a trade or profession and practice learning is consistently
highlighted by nursing and midwifery placement students for its impact on both
their professional and personal development. The paper examines the current
complexities of practice learning that have emerged from educational reform and
policy and debates the increased interest in the development of alternative
approaches to practice learning in the UK.
PMID- 28416144
TI - Feasibility of spirography features for objective assessment of motor function in
Parkinson's disease.
AB - OBJECTIVE: Parkinson's disease (PD) is currently incurable, however proper
treatment can ease the symptoms and significantly improve the quality of life of
patients. Since PD is a chronic disease, its efficient monitoring and management
is very important. The objective of this paper was to investigate the feasibility
of using the features and methodology of a spirography application, originally
designed to detect early Parkinson's disease (PD) motoric symptoms, for
automatically assessing motor symptoms of advanced PD patients experiencing motor
fluctuations. More specifically, the aim was to objectively assess motor symptoms
related to bradykinesias (slowness of movements occurring as a result of under
medication) and dyskinesias (involuntary movements occurring as a result of over
medication). MATERIALS AND METHODS: This work combined spirography data and
clinical assessments from a longitudinal clinical study in Sweden with the
features and pre-processing methodology of a Slovenian spirography application.
The study involved 65 advanced PD patients and over 30,000 spiral-drawing
measurements over the course of three years. Machine learning methods were used
to learn to predict the "cause" (bradykinesia or dyskinesia) of upper limb motor
dysfunctions as assessed by a clinician who observed animated spirals in a web
interface. The classification model was also tested for comprehensibility. For
this purpose a visualisation technique was used to present visual clues to
clinicians as to which parts of the spiral drawing (or its animation) are
important for the given classification. RESULTS: Using the machine learning
methods with feature descriptions and pre-processing from the Slovenian
application resulted in 86% classification accuracy and over 0.90 AUC. The
clinicians also rated the computer's visual explanations of its classifications
as at least meaningful if not necessarily helpful in over 90% of the cases.
CONCLUSIONS: The relatively high classification accuracy and AUC demonstrates the
usefulness of this approach for objective monitoring of PD patients. The positive
evaluation of computer's explanations suggests the potential use of this
methodology in a decision support setting.
PMID- 28416146
TI - Pseudomonas aeruginosa eradication: Finally moving the needle?
PMID- 28416145
TI - The Ginkgo biloba extract (GbE) protects the kidney from damage produced by a
single and low dose of carbon tetrachloride in adult male rats.
AB - Gingko biloba leaves have been used as herbal medicine in China for 5000 years,
and the standardized leaf extract (GB-STE) has some beneficial effects in the
treatment of age-related, cardiovascular, and neurological diseases. The aim of
this study was to investigate the renoprotective effects of the Gingko biloba
extract (GbE) against the toxicity of a single and relatively low dose of carbon
tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux,
the concentration of total proteins in urine, the concentration of glucose in
urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as
two markers of renal function (clearance of inulin and p-aminohippurate); we also
compared the histological lesions caused by CCl4. Carbon tetrachloride increased
the urinary concentration of total proteins, and the renal concentration of MDA;
however, it did not modify the urine flux, urinary concentration of glucose, nor
the inuline or the p-aminohipurate clearances. Morphologically, CCl4 generated
some tubular damage that was more intense in the inner cortex of kidneys. The GbE
extract counteracted the effects of CCl4 on the concentration of total proteins
in urine, the concentration of renal MDA, and the renal histological changes. In
conclusion the main toxic effects produced by CCl4 were prevented by the GbE,
probably due to their antioxidant properties and the inhibition of the main P450
isoenzyme (CYP2E1) that metabolize CCl4.
PMID- 28416147
TI - Response to: Madelung deformity.
PMID- 28416148
TI - Alterations in autonomic cerebrovascular control after spinal cord injury.
AB - Among chronic cardiovascular and metabolic sequelae of spinal cord injury (SCI)
is an up-to four-fold increase in the risk of ischemic and hemorrhagic stroke,
suggesting that individuals with SCI cannot maintain stable cerebral perfusion.
In able-bodied individuals, the cerebral vasculature is able to regulate cerebral
perfusion in response to swings in arterial pressure (cerebral autoregulation),
blood gases (cerebral vasoreactivity), and neural metabolic demand (neurovascular
coupling). This ability depends, at least partly, on intact autonomic function,
but high thoracic and cervical spinal cord injuries result in disruption of
sympathetic and parasympathetic cerebrovascular control. In addition, alterations
in autonomic and/or vascular function secondary to paralysis and physical
inactivity can impact cerebrovascular function independent of the disruption of
autonomic control due to injury. Thus, it is conceivable that SCI results in
cerebrovascular dysfunction that may underlie an elevated risk of stroke in this
population, and that rehabilitation strategies targeting this dysfunction may
alleviate the long-term risk of adverse cerebrovascular events. However, despite
this potential direct link between SCI and the risk of stroke, studies exploring
this relationship are surprisingly scarce, and the few available studies provide
equivocal results. The focus of this review is to provide an integrated overview
of the available data on alterations in cerebral vascular function after SCI in
humans, and to provide suggestions for future research.
PMID- 28416149
TI - Escalated anthracycline dose in adult AML.
PMID- 28416150
TI - Stem cell transplantation in multiple myeloma.
PMID- 28416151
TI - American Association for Cancer Research Annual Meeting 2017.
PMID- 28416152
TI - Which size of amplatz sheath should be used for pediatric percutaneous
nephrolithotomy cases?
PMID- 28416153
TI - A critical review of patient safety indicators attributed to trauma surgeons.
AB - BACKGROUND: The Agency for Health Care Research and Quality (AHRQ) developed
patient safety indicators (PSIs) to identify events with a high likelihood of
representing medical error. The purpose of this study was to validate PSIs
attributed to trauma surgeons and compare validated PSIs to performance
improvement (PI) and morbidity and mortality (M&M) data. We hypothesized that
PSIs are not an indicator of quality of care in trauma. METHODS: PSI's attributed
to trauma surgeons (n=9) at our institution were reviewed (Jan-Dec 2015). An
initial review was conducted to ensure they met inclusion and exclusion criteria
(valid). "Valid" PSIs were distributed to the trauma division for secondary
review. RESULTS: 48 PSIs were identified (17.2 per 1000 cases) during the study
period. 19 were false positives yielding a positive predictive value of 60% (95%
CI 45-74%). False positive PSIs were the result of coding error (78%), present on
admission status (17%) and documentation error (5%). Valid PSIs (n=29) were
further analyzed. The most common were post-op PE/DVT (n=14), failure to rescue
(n=6) and accidental puncture/laceration (n=3). 60% of patients with a post-op
PE/DVT were started on chemoprophylaxis on admission and 40% had significant
intracranial hemorrhage; all were deemed non-preventable through trauma PI. All
deaths considered failure to rescue were classified as expected mortalities
during M&M review. Although not clinically significant, all cases of accidental
puncture/laceration (10% of valid PSIs) represented opportunities for
improvement. CONCLUSION: Overall, PSIs have low validity and do not reflect
quality of care in trauma.
PMID- 28416154
TI - A comparison of dicarbonyl stress and advanced glycation endproducts in lifelong
endurance athletes vs. sedentary controls.
AB - OBJECTIVES: Dicarbonyl stress and high concentrations of advanced glycation
endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD).
Exercise training lowers the risk for future CVD. We tested the hypothesis that
lifelong endurance athletes have lower dicarbonyl stress and AGEs compared to
sedentary controls and that these differences relate to a better cardiovascular
health profile. DESIGN: Cross-sectional study. METHODS: We included 18 lifelong
endurance athletes (ATH, 61+/-7years) and 18 sedentary controls (SED, 58+/
7years) and measured circulating glyoxal (GO), methylglyoxal (MGO) and 3
deoxyglucosone (3DG) as markers of dicarbonyl stress. Furthermore, we measured
serum levels of protein-bound AGEs NE-(carboxymethyl)lysine (CML), NE
(carboxyethyl)lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and
pentosidine. Additionally, we measured cardiorespiratory fitness (VO2peak) and
cardiovascular health markers. RESULTS: ATH had lower concentrations of MGO (196
[180-246] vs. 242 [207-292] nmol/mmol lysine, p=0.043) and 3DG (927 [868-972] vs.
1061 [982-1114] nmol/mmol lysine, p<0.01), but no GO compared to SED. ATH
demonstrated higher concentrations CML and CEL compared to SED. Pentosidine did
not differ across groups and MG-H1 was significantly lower in ATH compared to
SED. Concentrations of MGO en 3DG were inversely correlated with cardiovascular
health markers, whereas CML and CEL were positively correlated with VO2peak and
cardiovascular health markers. CONCLUSION: Lifelong exercise training relates to
lower dicarbonyl stress (MGO and 3DG) and the AGE MG-H1. The underlying mechanism
and (clinical) relevance of higher CML and CEL concentrations among lifelong
athletes warrants future research, since it conflicts with the idea that higher
AGE concentrations relate to poor cardiovascular health outcomes.
PMID- 28416155
TI - Tracking of muscular strength and power from youth to young adulthood:
Longitudinal findings from the Childhood Determinants of Adult Health Study.
AB - OBJECTIVES: Low muscular fitness levels have previously been reported as an
independent risk factor for chronic disease outcomes. Muscular fitness tracking,
the ability to maintain levels measured at one point in time to another point in
time, was assessed from youth to adulthood to provide insight into whether early
identification of low muscular fitness in youth is possible. DESIGN: Prospective
longitudinal study. METHODS: Study including 623 participants who had muscular
fitness measures in 1985 (aged 9, 12 or 15 years) and again 20 years later in
young adulthood. Measures of muscular fitness were strength (right and left grip,
leg, shoulder extension and flexion measured by dynamometer, and a combined
strength score) and power (standing long jump distance). RESULTS: Strength and
power were relatively stable between youth and adulthood; the strongest tracking
correlations were observed for the combined strength score (r=0.47, p<=0.001),
right grip strength (r=0.43, p<=0.001) and standing long jump (r=0.43, p<=0.001).
Youth in the lowest third of muscular fitness had an increased risk of remaining
in the lowest third of muscular fitness in adulthood (strength: relative risk
(RR)=4.70, 95% confidence interval (CI) (3.19, 6.92); power: RR=4.06 (2.79,
5.90)). CONCLUSIONS: Youth with low muscular fitness are at increased risk of
maintaining a low muscular fitness level into adulthood. These findings warrant
investigation into the long term effects of early interventions that focus on
improving low muscular fitness levels in youth which could potentially improve
adult muscular fitness and reduce future chronic disease outcomes.
PMID- 28416156
TI - ?
PMID- 28416157
TI - Dentoskeletal sequellae after wearing of a mandibular advancement device in an
OSAHS setting.
AB - Mandibular advancement devices (MAD) are recommended in certain cases for the
treatment of obstructive sleep apnea and hypopnea syndrome (OSAHS). The aim of
this study was to make a retrospective investigation into the dental and skeletal
effects in patients suffering from OSAHS after wearing an MAD, and according to
the type of device, rigid or semi-rigid. Cephalometric criteria on lateral
cephalograms before and after at least 6 months of treatment were analyzed.
Twenty-two patients were included. We observed average labial tipping of the
lower incisors (+4.1+/-5.6 [P=0.0023]) and reduced overbite (-1.6+/-2.0mm
[P=0.0026]) and overjet (-1.4+/-2.3mm [P=0.0114]). Labial tipping of the
mandibular incisors was more pronounced with semi-rigid MAD. Similarly, the
decrease in overbite and overjet was more marked with the semi-rigid MAD. Medium
term wearing of MAD gives rise to dentally related occlusal changes, which can
only be corrected by orthodontic treatment.
PMID- 28416158
TI - ?
PMID- 28416159
TI - New finite element study protocol: Clinical simulation of orthodontic tooth
movement.
AB - The aim of this work was to model tooth movement in a more clinically-exact
fashion, thanks to the use of new IT tools and imaging systems (cone-beam). Image
segmentation and 3D reconstruction now enable us to model the anatomy
realistically, while finite element (FE) analysis makes it possible to evaluate
stresses and their distribution on the level of the tooth, the periodontal
ligament (PDL) and the alveolar bone when a force is applied. The principle is to
monitor tooth movement by obtaining optical impressions at each stage of
treatment. The model corresponds to a genuine clinical situation. FE analysis is
correlated with the clinically-observed displacement. The protocol remains long
and complex. It nevertheless makes it possible to obtain, throughout the duration
of treatment, patient-specific models that can be exploited using finite element
methods. It requires further validation in more thorough studies but offers
interesting prospects: precise study of induced tooth movement, distribution of
stresses in the PDL, and development of a customized previsualization tool.
PMID- 28416160
TI - The antidepressant-like effect of tDCS in mice: A behavioral and neurobiological
characterization.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive
method increasingly popular for the treatment of several brain disorders, such as
major depression. Despite great enthusiasm and promising results, some studies
report discrepant findings and no consensus exists for the clinical use of tDCS.
OBJECTIVE: The present study aims to (i) determine the most effective stimulation
parameters to optimize antidepressant-like effect of tDCS in the forced-swim test
in mice and (ii) identify brain regions recruited by tDCS and possibly involved
in its behavioral effect using Fos immunohistochemistry. RESULTS: We reported
that tDCS induced long-lasting antidepressant-like effect, which varied as a
function of stimulation settings including number, duration, intensity and
polarity of stimulation. Interestingly, the present study also demonstrated that
tDCS reduced depressive-like behaviors induced by chronic corticosterone
exposure. Furthermore, behavioral outcomes induced by a single stimulation were
associated with neuronal activation in the prefrontal cortex, dorsal hippocampus,
ventral tegmental area and nucleus accumbens, whereas no overexpression of c-fos
was associated with 10 stimulations. CONCLUSION: The strongest behavioral
response was observed with an anodal stimulation of 200 MUA during 20min. The
repetition of this stimulation was necessary to induce long-lasting behavioral
effects that are probably associated with plastic changes in the neuronal
response.
PMID- 28416161
TI - Cellular Senescence: A Translational Perspective.
AB - Cellular senescence entails essentially irreversible replicative arrest,
apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue
destructive senescence-associated secretory phenotype (SASP). Senescent cells
accumulate in various tissues with aging and at sites of pathogenesis in many
chronic diseases and conditions. The SASP can contribute to senescence-related
inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes,
chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent
cell accumulation or reducing senescent cell burden is associated with delay,
prevention, or alleviation of multiple senescence-associated conditions. We used
a hypothesis-driven approach to discover pro-survival Senescent Cell Anti
apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents,
drugs that cause senescent cells to become susceptible to their own pro-apoptotic
microenvironment. Several senolytic agents, which appear to alleviate multiple
senescence-related phenotypes in pre-clinical models, are beginning the process
of being translated into clinical interventions that could be transformative.
PMID- 28416162
TI - Pharmacokinetics of buprenorphine following constant rate infusion for
postoperative analgesia in dogs undergoing ovariectomy.
AB - OBJECTIVE: To investigate the pharmacokinetics of buprenorphine and its main
active metabolite, norbuprenorphine, after administration of an intravenous
loading dose followed by constant rate infusion (CRI) in dogs. STUDY DESIGN:
Prospective, clinical study. ANIMALS: A total of seven healthy dogs undergoing
elective ovariectomy. METHODS: Buprenorphine was administered as a loading dose
(intravenous bolus of 15 MUg kg-1) followed by CRI (2.5 MUg kg-1 hour-1 for 6
hours). Moreover, intraoperative analgesia was supplemented by an intramuscular
carprofen (4 mg kg-1) injection, administered prior to surgery, and by lidocaine,
administrated through subcutaneous infiltration and through a splash on the
ovarian vascular pedicle during surgery. Pain and sedation were scored for all
animals throughout the 24-hour study period and rescue analgesia was administered
when a visual analogue scale score was > 40 mm. Blood samples were collected from
a jugular catheter at regular intervals, and plasma concentrations of
buprenorphine and norbuprenorphine were determined by a validated liquid
chromatography-tandem mass spectrometry method. RESULTS: Buprenorphine showed a
two-compartment kinetic profile. Maximum concentration was 23.92 +/- 8.64 ng mL-1
at 1 minute (maximum time); elimination half-life was 41.87 +/- 17.35 minutes;
area under the curve was 486.68 +/- 125.66 minutes ng-1 mL-1; clearance was 33.61
+/- 13.01 mL minute-1 kg-1, and volume of distribution at steady state was 1.77
+/- 0.50 L kg-1. In no case was rescue analgesia required. Norbuprenorphine
resulted below the lower limit of quantification in almost all samples.
CONCLUSIONS AND CLINICAL RELEVANCE: The results suggest that a buprenorphine CRI
can be a useful tool for providing analgesia in postoperative patients,
considering its minor side effects and the advantages of a CRI compared to
frequent boluses. The negligible contribution of norbuprenorphine to the
therapeutic effect was confirmed.
PMID- 28416163
TI - Nanosheets for Delivery of Biomolecules into Plant Cells.
AB - Layered double hydroxides (LDHs) are sheet-formed nanoparticles (NPs) of
adjustable size. It has recently been reported that LDHs have the ability to
deliver biomolecules into intact plant cells. LDHs show promise as a novel and
powerful tool for plant cell studies and similar applications.
PMID- 28416164
TI - Morphological variability of the earlobe in a Spanish population sample.
AB - This article shows the morphological variability of the earlobe in a Spanish
population of European origin. The frequencies of four lobe characteristics
(attachment, contour, modeling, and size) and their degree of expression were
studied. The relationship among the characteristics and the differences involving
sex and laterality were also considered. The least frequent morphology, and of
main use in solving forensic cases, was the very small size with triangle-pulled
contour into the skin and crossed-discontinuous modeling. The most frequent
morphology, and most clinically useful, was the medium-sized lobe with free
arched contour and eminent or cross-continuous modeling. The characteristics were
all symmetric. Size and modeling showed sexual dimorphism. Some characteristics
were associated with each other: attachment with contour and modeling and the
contour with modeling and size. The least frequent peculiarities were sharp lobe
and virgule. The literature is scarce on this matter, practically non-existent
for some characteristics, especially modeling and peculiarities. For the first
time, the associations of the ear characteristics were analyzed, and this
information could be applied to forensic identification.
PMID- 28416165
TI - Influence of Cardiovascular Risk in the Prediction and Timing of Cardiac Events
After Exercise Echocardiogram Testing Without Ischemia.
AB - INTRODUCTION AND OBJECTIVES: There have been no analyses of the influence of
cardiovascular risk as a predictor of events in patients with exercise
echocardiography (EE) without ischemia. Our objective was to determine the
predictors of cardiac events, paying special attention to cardiovascular risk.
METHODS: This study included 1640 patients with EE without ischemia. Of these,
there were 1206 with no previously known coronary artery disease (CAD), whose
risk of a fatal cardiovascular disease event was estimated according to the
European SCORE (Systematic COronary Risk Evaluation) risk assessment system, and
434 with known CAD. The primary endpoint was cardiac event-free survival (EFS)
(cardiac death, nonfatal acute coronary syndrome, and coronary
revascularization). RESULTS: After a median follow-up of 35 [23-54] months, no
differences were found in cardiac EFS between patients with a SCORE >= 10 or
diabetes and patients with previous CAD (89.8% vs 87.1%). In the first year,
cardiac EFS was high in all groups (99.4% if SCORE < 5; 100% if 5-9; 98% if >= 10
or diabetes and 97% in patients with CAD). In the third year, cardiac EFS was
similar in the group with SCORE >= 10 or diabetes (94.5%) and patients with CAD
(91.1%, P = NS). In these patients, the annualized event rate was 2.8% and 2.55%,
respectively, and was significantly higher than in groups with SCORE < 5 (0.6%)
and SCORE 5-9 (0.12%). The most frequent events were non-ST-segment elevation
acute coronary syndrome and late revascularization. Predictors of cardiac events
were previous CAD, SCORE >= 10 or diabetes mellitus, creatinine clearance, left
ventricular ejection fraction, and chest pain during EE. CONCLUSIONS: Initial
outcome after an EE without ischemia is favorable but is subsequently modulated
by cardiovascular risk.
PMID- 28416166
TI - Two-year outcomes of balloon-occluded retrograde transvenous obliteration of
gastric varices in liver transplant recipients: A multi-institutional study.
AB - PURPOSE: To assess the 2-year effectiveness and safety of balloon-occluded
retrograde transvenous obliteration (BRTO) for gastric varices (GVs) in liver
transplant recipients. MATERIALS AND METHODS: Eleven liver transplant recipients
underwent consecutive BRTO for GVs at four institutions. Patients included eight
(73%) men and three (27%) women with mean age of 56 years+/-12 (SD) (range: 26-67
years). Underlying cause of liver transplantation was hepatitis C virus (HCV)
related cirrhosis in five (45%), alcohol- and HCV-related cirrhosis in three
(27%), primary biliary cirrhosis in two (18%), and alcoholic cirrhosis in one
(9%). Five (45%) patients underwent BRTO for actively bleeding GVs, three (17%)
for high-risk GVs, and three (17%) for augmentation of portal venous flow through
obliteration of gastrorenal shunts. Mean time between liver transplantation and
BRTO was 78 months (range: 0.1-276 months). Technical success, GVs obliterative
rates, and immediate complications were recorded. Post-BRTO hemorrhagic,
transplant, and overall survival rates were evaluated at 6, 12, and 24 months.
RESULTS: All (100%) procedures were technically successful. Complete GVs
obliteration was achieved in ten patients (91%). Two major complications (18%)
occurred in the immediate post-procedure period. One patient developed complete
portal vein thrombosis, and another patient developed consumptive coagulopathy,
ultimately leading to death. No post-BRTO hemorrhagic recurrences were seen at 6,
12, or 24 months. One patient (9%) had delayed upper gastrointestinal bleeding at
34 months after the procedure which was managed conservatively. Transplant and
overall survival rates were 91% at 6, 12, and 24 months. CONCLUSION: BRTO has
high technical success and complete GVs obliterative rates in liver transplant
recipients with few complications and high graft survival rates.
PMID- 28416167
TI - Partial reinforcement of avoidance and resistance to extinction in humans.
AB - In anxiety, maladaptive avoidance behavior provides for near-perfect
controllability of potential threat. There has been little laboratory-based
treatment research conducted on controllability as a contributing factor in the
transition from adaptive to maladaptive avoidance. Here, we investigated for the
first time whether partial reinforcement rate, or the reliability of avoidance at
controlling or preventing contact with an aversive event, influences subsequent
extinction of avoidance in humans. Five groups of participants were exposed to
different partial reinforcement rates where avoidance cancelled upcoming shock on
100%, 75%, 50%, 25% or 0% of trials. During extinction, all shocks were withheld.
Avoidance behavior, online shock expectancy ratings and skin conductance
responses (SCRs) were measured throughout. We found that avoidance was a function
of relative controllability: higher reinforcement rate groups engaged in
significantly more extinction-resistant avoidance than lower reinforcement
groups, and shock expectancy was inversely related with reinforcement rate during
avoidance acquisition. Partial reinforcement effects were not evident in SCRs.
Overall, the current study highlights the clinical relevance of laboratory-based
treatment research on partial reinforcement or controllability effects on
extinction of avoidance.
PMID- 28416168
TI - Non-invasive preimplantation genetic screening using array comparative genomic
hybridization on spent culture media: a proof-of-concept pilot study.
AB - The aim of this pilot study was to assess if array comparative genomic
hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on
blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on
22 spent blastocyst culture media samples after polar body PGS because of
advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm
injection and all embryos underwent assisted hatching. Concordance of polar body
analysis and culture media genetic results was assessed. Thirteen out of 18
samples (72.2%) revealed general concordance of ploidy status (euploid or
aneuploid). At least one chromosomal aberration was found concordant in 10 out of
15 embryos found to be aneuploid by both polar body and culture media analysis.
Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant
between the culture media and polar body analysis. By analysing negative controls
(oocytes with fertilization failure), notable maternal contamination was
observed. Therefore, non-invasive PGS could serve as a second matrix after polar
body or cleavage stage PGS; however, in euploid results, maternal contamination
needs to be considered and results interpreted with caution.
PMID- 28416169
TI - Pathologic fracture of the thoracic spine in a male master ultra-marathoner due
to the combination of a vertebral hemangioma and osteopenia.
AB - Vertebral hemangiomas are the most common benign vertebral neoplasms and are
generally asymptomatic. In the present study, we report the case of a 52-year-old
male master ultra-marathoner suffering from a pathologic fracture of the thoracic
spine due to a vertebral hemangioma. A further examination in the athlete
revealed an accompanying osteopenia, which was most likely due to a deficiency in
both vitamin D and testosterone. The treatment of the fracture consisted of
percutaneous vertebroplasty. Shortly after the operation the athlete was able to
continue running. The most likely reason for the pathologic fracture of the
vertebral body was the combination of the vertebral hemangioma and osteopenia.
The further treatment consisted of supplementation of both vitamin D and
testosterone. Athletes and physicians should be aware that male master ultra
marathoners older than 50 years might suffer from osteopenia, where a deficiency
in vitamin D and testosterone could be contributing factors for osteopenia
development in general.
PMID- 28416170
TI - Hepcidin serum levels and resistance to recombinant human erythropoietin therapy
in hemodialysis patients.
AB - OBJECTIVE: The aim of this study was to analyze the factors that are associated
with the response to erythropoiesis-stimulating agents (ESAs) and its association
with hospitalization and mortality rates; to evaluate the serum hepcidin level
and its associations with iron profile, inflammatory markers, ESA responsiveness,
and mortality; and to determine independent factors affecting ERI and hepcidin.
MATERIALS AND METHODS: To evaluate a dose-response effect of ESAs we used the
erythropoietin resistance index (ERI). Patients were stratified in two groups:
nonresponders and responders (ERI>15, n=20, and ERI <=15U/kg/week/g per 100mL,
n=153, respectively). Hematological data, hepcidin levels, iron parameters,
inflammatory markers, hospitalization and mortality rates were compared between
the groups. Multiple regression analysis was used to determine independent
factors affecting ERI and hepcidin. RESULTS: C-reactive protein (CRP)
(beta=0.078, P=0.007), albumin (beta=-0.436, P=0.004), body mass index (beta=
0.374, P<0.001), and hospitalization rate per year (beta=3.017, P<0.001) were
found to be significant determinants of ERI in maintenance hemodialysis (MHD)
patients. Inadequate dialysis was associated with higher ERI. Patients with
concomitant oncological diseases had higher ERI (31.2+/-12.4 vs 9.7+/
8.1U/kg/week/g per 100mL, P=0.002). The hepcidin level was 158.51+/-162.57 and
120.65+/-67.28ng/mL in nonresponders and responders, respectively (P=0.33).
Hepcidin correlated directly with ERI, dose of ESAs, ferritin and inversely with
Hb, transferrin saturation, and albumin. ERI (beta=4.869, P=0.002) and ferritin
(beta=0.242, P=0.003) were found to be significant determinants of hepcidin in
MHD patients. The hospitalization rate per year was 2.35+/-1.8 and 1.04+/-1.04 in
nonresponders and responders, respectively (P=0.011). The mean length of one
hospitalization was 25.12+/-21.26 and 10.82+/-17.25 days, respectively (P=0.012).
Death occurred in 30% of the patients from the responders' group and in 50% from
the nonresponders' group (P=0.289). The mean hepcidin concentration of patients
who died was 141.9+/-129.62ng/mL and who survived, 132.98+/-109.27ng/mL
(P=0.797). CONCLUSIONS: CRP, albumin, BMI, and hospitalization rate per year were
found to be significant determinants of ERI in MHD patients. Inadequate dialysis
was associated with higher epoetin requirements. There were no difference in
patient mortality by ERI, but a significant difference in hospitalization rates
and mean length of one hospitalization was revealed. A significant positive
relation between hepcidin and ERI was revealed. ERI and ferritin were found to be
significant determinants of hepcidin in MHD patients. Hepcidin was not related to
mortality.
PMID- 28416171
TI - The comparison of knee osteoarthritis treatment with single-dose bone marrow
derived mononuclear cells vs. hyaluronic acid injections.
AB - OBJECTIVE: The aim of this study was to compare treatment methods of the knee
joint degenerative osteoarthritis, using autologous bone marrow-derived
mononuclear cells and hyaluronic acid injections and observe prevalence of
adverse effects in both groups. MATERIALS AND METHODS: A prospective randomized
controlled clinical trial was carried out. The analysis of pain and changes in
osteoarthritis symptoms after a single intra-articular bone marrow-derived
mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II
III osteoarthritis during the 12-month period were performed. The results were
compared with the control group treated routinely by hyaluronic acid injections
therapy. A therapy group of patients (n=28) received single bone marrow-derived
mononuclear cell intra-articular injections. A control group of patients (n=28)
was treated with a total of three sodium hyaluronate intra-articular injections
each one performed a week apart. The clinical results were obtained using the
Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before
and 3, 6, and 12 months after injection. RESULTS: A statistically significant
improvement was observed in the mononuclear cell group over the starting point in
all scores. At the endpoint at month 12, the KOOS score improved significantly
(P<0.05) on the pain subscale (+25.44), activity and daily living subscale
(+21.36), quality of life subscale (+28.83), and total KOOS (+18.25). The KSS
score also demonstrated a significant improvement on the symptoms subscale
(+25.42) and the function subscale (+38.32) (P<0.001). The KOOS symptoms and
sports subscales improved without statistical significance. The difference
between the control group treated with hyaluronic acid versus the bone marrow
derived mononuclear cells group at time points 6 and 12 months demonstrated a
statistically significant (P<0.05) superiority in the KOOS pain subscale over the
hyaluronic acid group. In both groups serious adverse effects were not observed.
CONCLUSIONS: The intra-articular injection of bone marrow-derived mononuclear
cells is a safe manipulation with no side effects during the 12-month period.
This treatment provides statistically significant clinical improvement between
the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic
acid treatment, better pain relief in the long-term period of mononuclear cell
group was observed.
PMID- 28416172
TI - Epidemiology of ebolavirus disease (EVD) and occupational EVD in health care
workers in Sub-Saharan Africa: Need for strengthened public health preparedness.
AB - Ebolavirus disease (EVD) is a severe contagious disease in humans, and health
care workers (HCW) are at risk of infection when caring for EVD patients. This
paper highlights the epidemiologic profile of EVD and its impact on the health
care workforce in Africa. A documentary study was conducted which consisted of a
review of available literature regarding the epidemiology of EVD, occupational
EVD (OEVD), and work safety issues in Sub-Saharan Africa; the literature findings
are enriched by field experiences from the authors. EVD outbreaks have already
caused 30,500 cases in humans of whom 12,933 died (as of September 9, 2015), and
the number of infected HCW has dramatically increased. All eight HCW infected
during the 2014 outbreak in Democratic Republic of the Congo died, whereas during
the recent West African EVD epidemic more than 890 HCW were infected, with a case
fatality rate of 57%. Occupational exposure to blood and other body fluids due to
inadequate use of personal protective equipment and needle stick or sharp
injuries are among factors that contribute to the occurrence of OEVD. Prevention
of OEVD should be one of the top priorities in EVD outbreak preparedness and
management, and research should be conducted to elucidate occupational and other
factors that expose HCW to EVD. In addition to regularly training HCW to be
adequately prepared to care for patients with EVD, it is critical to strengthen
the general health care system and improve occupational safety in medical
settings of countries at risk.
PMID- 28416173
TI - [Cardiac arrest animal model: a simple device for small animals' chest
compression].
PMID- 28416174
TI - [Ultrasound guided quadratus lumborum block for analgesia after cesarean
delivery: case series].
AB - INTRODUCTION: The majority of women having planned cesarean section receive
spinal anesthesia for the procedure. Typically, spinal opioids are administered
during the same time as a component of multimodal analgesia to provide pain
relief in the 16-24h period postoperatively. The quadratus lumborum block is a
regional analgesic technique that blocks T5-L1 nerve branches and has an evolving
role in postoperative analgesia for lower abdominal surgeries and may be a
potential alternative to spinal opioids. If found effective, it will have the
advantage of a reduction in opioid associated adverse effects while providing
similar quality of analgesia. METHODS: We performed bilateral quadratus lumborum
block in 3 women who received a spinal anesthetic for a cesarean delivery and
evaluated their post-operative opioid consumption and patient satisfaction.
RESULTS: In all 3 patients, there was no additional opioid consumption during the
first 24h after the block. Numeric Rating Scale (NRS) for pain was less than 6
for the first 24h. Women were all very satisfied with the quality of pain relief.
DISCUSSION: Quadratus lumborum block may be a promising anesthetic adjuvant for
post-cesarean analgesia. Further randomized controlled trials are needed to
compare the efficacy of the quadratus lumborum block with intrathecal opioids.
PMID- 28416175
TI - Corneal Endothelial Cell Density in Children: Normative Data From Birth to 5
Years Old.
PMID- 28416176
TI - Maternal early warning systems-Towards reducing preventable maternal mortality
and severe maternal morbidity through improved clinical surveillance and
responsiveness.
AB - Despite increasing awareness of obstetric safety initiatives, maternal mortality
and severe maternal morbidity in the United States have continued to increase
over the past 20 years. Since results from large-scale surveillance programs
suggest that up to 50% of maternal deaths may be preventable, new efforts are
focused on developing and testing early warning systems for the obstetric
population. Early warning systems are a set of specific clinical signs or
symptoms that trigger the awareness of risk and an urgent patient evaluation,
with the goal of reducing severe morbidity and mortality through timely diagnosis
and treatment. Early warning systems have proven effective at predicting and
reducing mortality and severe morbidity in medical, surgical, and critical care
patient populations; however, there has been limited research on how to adapt
these tools for use in the obstetric population, where physiologic changes of
pregnancy render them inadequate. In this article, we review the available
obstetric early warning systems and present evidence for their use in reducing
maternal mortality and severe maternal morbidity. We also discuss considerations
and strategies for implementation and acceptance of these early warning systems
for clinical use in obstetrics.
PMID- 28416177
TI - Restoring: How older adults manage their recovery from hip fracture.
AB - AIMS AND OBJECTIVES: To generate a substantive theory that explained recovery
from hip fracture from the perspective of older adults and find out how they
managed it. BACKGROUND: Hip fracture is a well-researched phenomenon. The
perspective of how older adults recover from hip fracture has been examined least
of all. Patients spend less time in hospital following injury and generally
recover in their home setting. DESIGN: A Glaserian grounded theory approach was
used for this study. METHODS: Semi-structured interviews (n-21) were conducted
with older adult's post discharge following hip fracture. Data were collected,
analysed and theorised using the grounded theory methodology. RESULTS: Older
adults recovering from hip fracture were restored back to normal through a
process in which they continuously balanced regaining of physical and social
functioning against reasserting usual psycho-social behaviours within different
contexts. Importantly, the older adult's personal recovery process starts within
the acute setting once the person regains physical functioning, especially
regaining mobility. From this point onwards, older adults will respond to health
professionals, instructions and interventions in many ways. The responses will be
based on their developmental life stage to enable them to counter the diverse
expectations placed on them by health professionals, social networks and their
self-beliefs. CONCLUSION: Nurses need to understand that older adults will
recover in their own way following discharge, often re-interpreting health
information to fit their own situations.
PMID- 28416178
TI - The effect of time to surgery on functional ability at six weeks in a hip
fracture population in Mid-West Ireland.
AB - Patients with a hip fracture may be appropriately delayed for surgery as they
require optimisation or clinical interventions to treat acute medical illnesses
(Moja et al., 2012). Other patients are inappropriately delayed due to hospital
factors (Brener, 2013; Lee & Elfar, 2014). Timely efficient admission and surgery
is well documented as the best course of management for these patients. The aim
of this prospective cohort longitudinal follow-up study was to establish if a
relationship existed between duration of time spent in the Emergency Department
(ED), time to surgery and functional ability in patients with hip fractures and
to examine the effect prolonged waits may have on ability to return home.
Functional ability for fifty one patients with a hip fracture was evaluated using
the Barthel Index Score (BIS) on admission and at six weeks post-surgery. Data
were analysed by using SPSS version 20. The findings reveal a change in BIS at 6
weeks for patients whose surgery is delayed. Patients who experienced long delays
awaiting admission (>12 h) in the ED functioned less well (Kruskal-Wallis test p
= 0.033). Correlation existed between time to surgery and returning to pre
fracture place of residence, (p = 0.000 Pearson chi-square), which also remained
significant while controlling for age. Prolonged waits had an overall negative
impact on patients' post-fracture functional ability. This study highlights the
deleterious effects on functional ability when surgery is delayed.
PMID- 28416179
TI - Increased risk of ventral hernia recurrence after pregnancy: A nationwide
register-based study.
AB - BACKGROUND: Female patients of reproductive age constitute a substantial portion
of patients undergoing ventral hernia repair, however the impact of pregnancy on
the risk of recurrence is scarcely documented. The aim of the study was to
evaluate if pregnancy following ventral hernia repair was associated with an
increased risk of recurrence. METHODS: This nationwide cohort study included all
female patients of reproductive age registered in the Danish Ventral Hernia
Database with ventral hernia repair between 2007 and 2013. The primary outcome
was ventral hernia recurrence. Multivariable extended Cox regression analysis was
performed. RESULTS: A total of 3578 patients were included in the study, 267
(7.5%) of whom subsequently became pregnant during follow-up. The median follow
up was 3.1 years (range 0-8.4 years). Pregnancy was independently associated with
recurrence (hazard ratio 1.56, 95% confidence interval 1.09-2.25, P = 0.016).
CONCLUSIONS: Pregnancy after ventral hernia repair was independently associated
with ventral hernia recurrence.
PMID- 28416180
TI - Revision of sleeve gastrectomy to Roux-en-Y Gastric Bypass: A Canadian
experience.
AB - INTRODUCTION: Sleeve gastrectomy (SG) can be associated with inadequate weight
loss, insufficient resolution of co-morbidities and severe reflux. Conversion to
Roux-en-Y Gastric Bypass (RYGB) is a potential solution. The aim of this study
was to determine the common indications for conversion from SG to RYGB at our
centre, and evaluate patient outcomes with respect to weight loss and co
morbidity resolution. METHODS: A retrospective review of patients who underwent
conversion from SG to RYGB between 2008 and 2015. RESULTS: 273 SGs were performed
of which 6.6% (n = 18) were converted to RYGB most commonly due to inadequate
weight loss (65.3%) and severe reflux (26.1%). Two patients were converted as a
planned two-stage approach to RYGB. Patients went from a mean preoperative BMI of
50.5 to a mean BMI of 40.5 post-SG on average by 20.9 months. The mean time to
conversion was 41.8 months. There was a positive correlation between pre-SG BMI
and time to conversion (p = 0.040). The mean BMI after conversion was 36.4, but
this additional weight loss was not significant (p = 0.057). After conversion,
four of the five diabetic patients are now medication free and 75% of patients no
longer have reflux symptoms. All patients had complete resolution of their
hypertension and obstructive sleep apnea. Revision perioperative complication
rates were comparable to primary RYGB. Two patients developed new onset iron
deficiency anemia. CONCLUSION: Revision to RYGB is a safe option for SG failure
and resulted in significant benefits from co-morbidity resolution.
PMID- 28416181
TI - A comparison of a novel robust decentralised control strategy and MPC for
industrial high purity, high recovery, multicomponent distillation.
AB - In this work we have developed a novel, robust practical control structure to
regulate an industrial methanol distillation column. This proposed control scheme
is based on a override control framework and can manage a non-key trace ethanol
product impurity specification while maintaining high product recovery. For
comparison purposes, a MPC with a discrete process model (based on step tests)
was also developed and tested. The results from process disturbance testing shows
that, both the MPC and the proposed controller were capable of maintaining both
the trace level ethanol specification in the distillate (XD) and high product
recovery (beta). Closer analysis revealed that the MPC controller has a tighter
XD control, while the proposed controller was tighter in beta control. The tight
XD control allowed the MPC to operate at a higher XD set point (closer to the
10ppm AA grade methanol standard), allowing for savings in energy usage. Despite
the energy savings of the MPC, the proposed control scheme has lower installation
and running costs. An economic analysis revealed a multitude of other external
economic and plant design factors, that should be considered when making a
decision between the two controllers. In general, we found relatively high energy
costs favour MPC.
PMID- 28416182
TI - Dynamical tuning for MPC using population games: A water supply network
application.
AB - Model predictive control (MPC) is a suitable strategy for the control of large
scale systems that have multiple design requirements, e.g., multiple physical and
operational constraints. Besides, an MPC controller is able to deal with multiple
control objectives considering them within the cost function, which implies to
determine a proper prioritization for each of the objectives. Furthermore, when
the system has time-varying parameters and/or disturbances, the appropriate
prioritization might vary along the time as well. This situation leads to the
need of a dynamical tuning methodology. This paper addresses the dynamical tuning
issue by using evolutionary game theory. The advantages of the proposed method
are highlighted and tested over a large-scale water supply network with periodic
time-varying disturbances. Finally, results are analyzed with respect to a multi
objective MPC controller that uses static tuning.
PMID- 28416183
TI - Inhibition of the in vitro growth of Babesia bigemina, Babesia caballi and
Theileria equi parasites by trifluralin analogues.
AB - Bovine and equine babesiosis caused by Babesia bovis, Babesia bigemina and
Babesia caballi, along with equine theileriosis caused by Theileria equi are
global tick-borne hemoprotozoan diseases characterized by fever, anemia, weight
losses and abortions. A common feature of these diseases are transition from
acute to chronic phases, in which parasites may persist in the hosts for life.
Antiprotozoal drugs are important for managing infection and disease. Previous
research demonstrated that trifluralin analogues, designated (TFLAs) 1-15, which
specifically bind to regions of alpha-tubulin protein in plants and protozoan
parasites, have the ability to inhibit the in vitro growth of B. bovis. The
inhibitory activity of TFLAs 1-15 minus TFLA 5 was tested in vitro against
cultured B. bigemina, B. caballi and T. equi. The four TFLAs with greatest
inhibitory activity were then analyzed for hemolytic activity and toxicity
against erythrocytes. All TFLAs tested in the study showed inhibitory effects
against the three parasite species. TFLA 2, TFLA 11, TFLA 13 and TFLA 14 were the
most effective inhibitors for the three species tested, with estimated IC50
between 5.1 and 10.1MUM at 72h. The drug's solvent (DMSO/ethanol) did not
statistically affect the growth of the parasites nor cause hemolysis. Also, TFLA
2, 13 and 14 did not cause statistically significant hemolytic activity on bovine
and equine erythrocytes at 15MUM, and TFLA 2, 11 and 13 had no detectable toxic
effects on bovine and equine erythrocytes at 15MUM, suggesting that these drugs
do not compromise erythrocyte viability. The demonstrated ability of the
trifluralin analogues to inhibit in vitro growth of Babesia spp. and Theileria
equi, and their lack of toxic effects on erythrocytes supports further in vivo
testing and eventually their development as novel alternatives for the treatment
of babesiosis and theileriosis.
PMID- 28416185
TI - American Society for Metabolic and Bariatric Surgery position statement on the
impact of obesity and obesity treatment on fertility and fertility therapy
Endorsed by the American College of Obstetricians and Gynecologists and the
Obesity Society.
PMID- 28416186
TI - Nutritional deficiencies four years after laparoscopic sleeve gastrectomy-are
supplements required for a lifetime?
AB - BACKGROUND: Data regarding long-term nutritional deficiencies following
laparoscopic sleeve gastrectomy (LSG) are scarce. OBJECTIVES: To assess the
prevalence of nutritional deficiencies and supplement consumption 4 years post
LSG. SETTING: Hebrew University, Israel. METHODS: Data were collected
prospectively from preoperative and 1 and 4 years postoperative including
anthropometric parameters, biochemical tests, and supplement intake. RESULTS:
Data were available for 192, 77, and 27 patients at presurgery and 1 and 4 years
post-LSG, respectively. Prevalence of nutritional deficiencies at baseline and 1
and 4 years postsurgery, respectively, were specifically for iron (44%, 41.2%,
28.6%), anemia (11.5%, 20%, 18.5%), folate (46%, 14.3%, 12.5%), vitamin B12
(7.7%, 13.6%, 15.4%), vitamin D (96.2%, 89%, 86%), and elevated parathyroid
hormone (PTH) (52%, 15.4%, 60%). Vitamin D levels remained low throughout the
whole period. PTH levels were 37.5 pg/mL at 1 year postsurgery and increased to
77.3 pg/mL at 4 years postsurgery (P = .009). Females had higher prevalence of
elevated PTH and a tendency for higher rates of anemia, compared with males 4
years postsurgery (80% versus 20%, P = .025; and 28% versus 0%, P = .08,
respectively). Of the patients, 92.6% reported taking a multivitamin and 74.1%
vitamin D supplements during the first postoperative year, while after 4 years
only 37% and 11.1% were still taking these supplements, respectively. CONCLUSION:
A high rate of nutritional deficiencies is common at 4 years post-LSG along with
low adherence to the nutritional supplementation regimen. Long-term nutritional
follow-up and supplementation maintenance are crucial for LSG patients. Future
studies are needed to clarify the clinical impact of such deficiencies.
PMID- 28416184
TI - TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in
the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells.
AB - Aberrant WNT signaling drives colorectal cancer (CRC). Here, we identify TIAM1 as
a critical antagonist of CRC progression through inhibiting TAZ and YAP,
effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the
cytoplasm and nucleus antagonizing TAZ/YAP by distinct mechanisms in the two
compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and
promotes TAZ degradation by enhancing its interaction with betaTrCP. Nuclear
TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP
target genes implicated in epithelial-mesenchymal transition, cell migration, and
invasion, and consequently suppresses CRC cell migration and invasion.
Importantly, high nuclear TIAM1 in clinical specimens associates with increased
CRC patient survival. Together, our findings suggest that in CRC TIAM1 suppresses
tumor progression by regulating YAP/TAZ activity.
PMID- 28416187
TI - Comment: Value of routine upper gastrointestinal swallow study after laparoscopic
sleeve gastrectomy.
PMID- 28416188
TI - A giraffe neck sign of the medial meniscus: A characteristic finding of the
medial meniscus posterior root tear on magnetic resonance imaging.
AB - BACKGROUND: The posterior root ligament of the medial meniscus (MM) has a
critical role in regulating the MM movement. An accurate diagnosis of the MM
posterior root tear (MMPRT) using magnetic resonance imaging (MRI) is important
for preventing sequential osteoarthritis following the MMPRT. However, diagnosis
of the MMPRT is relatively difficult even after using several characteristic MRI
findings. The aim of this study was to identify a useful meniscal body sign of
the MMPRT for improving diagnostic MRI reading. METHODS: Eighty-five patients who
underwent surgical treatments for the MMPRT (39 knees) and other types of MM
tears (49 knees) were included. The presence of characteristic MRI findings such
as cleft sign, ghost sign, radial tear sign, medial extrusion sign, and new
meniscal body shape-oriented "giraffe neck sign" was evaluated in 120 MRI
examinations. RESULTS: Giraffe neck signs were observed in 81.7% of the MMPRTs
and in 3.3% of other MM tears. Cleft, ghost, and radial tear signs were highly
positive in the MMPRTs compared with other MM tears. Medial extrusion signs were
frequently observed in both groups. Coexistence rates of any 2 MRI signs, except
for medial extrusion sign, were 91.7% in the MMPRT group and 5% in other MM
tears. CONCLUSIONS: This study demonstrated that a new characteristic MRI finding
"giraffe neck sign" was observed in 81.7% of the MMPRT. Our results suggest that
the combination of giraffe neck, cleft, ghost, and radial tear signs may be
important for an accurate diagnostic MRI reading of the MMPRT.
PMID- 28416189
TI - The validity and reliability of the Arabic version of the Japanese Orthopedic
Association Back Pain Evaluation Questionnaire: Can we implement it in Saudi
Arabia?
AB - BACKGROUND: The Japanese Orthopedic Association designed their back pain
evaluation questionnaire (JOABPEQ) which was proven to be feasible, reliable and
valid. The questionnaire's validity and reliability were confirmed when it was
implemented in patients with different cultural background. Since the JOABPEQ
still has not been utilized in any of the Arabic countries, we present the Arabic
version with its validity and reliability. METHODS: After ensuring an optimal
forward-backward translation of the JOABPEQ, the Arabic version was distributed
among 151 patients visiting our clinics from December 2015 to February 2016. The
reliability was tested using Cronbach's alpha. The convergent validity was
assessed through aggregating and correlating the questionnaire's items with their
previously designed and validated subscales described in the JOABPEQ validity
study by Fukui et al. (four items for social function, seven for mental health,
six for lumbar function, five for walking ability and four for low back pain);
Spearman's correlation matrix was used. The correlation coefficient had to be
greater than 0.40 for each item with its corresponding subscale to be
satisfactory. Scores underwent descriptive analysis, and Mann-Whitney u test was
performed to compare between categorical subgroups. RESULTS: 151 spine patients
completed the questionnaire. The mean age (range) was 34.9 (10-72) years. The
male respondents were 61 (40.4%) and the females were 90 (59.6%). The result of
Cronbach's alpha for internal consistency (reliability) was 0.87 for the 25
items. The validity was confirmed since the correlation coefficient was greater
than 0.4 for each item with only its relevant subscale. CONCLUSION: the Arabic
version of the JOABPEQ is valid, reliable and feasible in assessing patients with
spine disorders. We believe the JOABPEQ with its different versions are suitable
questionnaires to be used across nations and can serve as a unified tool in
conducting research and exchanging information in the future.
PMID- 28416190
TI - Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms.
AB - OBJECTIVE/BACKGROUND: Biomarker(s) for prediction of the future progression rate
of abdominal aortic aneurysms (AAA) may be useful to stratify the management of
individual patients. AAAs are associated with features of systemic inflammation
and endothelial dysfunction. Flow mediated dilatation (FMD) of the brachial
artery is a recognised non-invasive measurement for endothelial function. We
hypothesised that FMD is a potential biomarker of AAA progression and reflects
the temporal changes of endothelial function during AAA progression. METHODS: In
a prospectively recruited cohort of patients with AAAs (Oxford Abdominal Aortic
Aneurysm Study), AAA size was recorded by antero-posterior diameter (APD) (outer
to outer) on ultrasound. Annual AAA progression was calculated by (DeltaAPD/APD
at baseline)/(number of days lapsed/365 days). FMD was assessed at the same time
as AAA size measurement. Analyses of data were performed in the overall cohort,
and further in subgroups of AAA by size (small: 30-39 mm; moderate: 40-55 mm;
large: > 55 mm). RESULTS: FMD is inversely correlated with the diameter of AAAs
in all patients (n=162, Spearman's r=-.28, p<.001). FMD is inversely correlated
with AAA diameter progression in the future 12 months (Spearman's r=-.35,
p=.001), particularly in the moderate size group. Furthermore, FMD deteriorates
during the course of AAA surveillance (from a median of 2.0% at baseline to 1.2%
at follow-up; p=.004), while surgical repair of AAAs (n=50 [open repair n=22,
endovascular repair n=28)] leads to an improvement in FMD (from 1.1% pre
operatively to 3.8% post-operatively; p<.001), irrespective of the type of
surgery. CONCLUSION: FMD is inversely correlated with future AAA progression in
humans. FMD deteriorates during the natural history of AAA, and is improved by
surgery. The utility of FMD as a potential biomarker in the context of AAA
warrants further investigation.
PMID- 28416192
TI - Corrigendum to: Georgia's Medicaid Family Planning Waiver: Working Together with
Title X to Enhance Access to and Use of Contraceptive and Preventive Health
Services [Women's Health Issues 26 (2016) 602-611].
PMID- 28416191
TI - Editor's Choice - Assessment of International Outcomes of Intact Abdominal Aortic
Aneurysm Repair over 9 Years.
AB - BACKGROUND: Case mix and outcomes of complex surgical procedures vary over time
and between regions. This study analyses peri-operative mortality after intact
abdominal aortic aneurysm (AAA) repair in 11 countries over 9 years. METHODS:
Data on primary AAA repair from vascular surgery registries in 11 countries for
the years 2005-2009 and 2010-2013 were analysed. Multivariate adjusted logistic
regression analyses were carried out to adjust for variations in case mix.
RESULTS: A total of 83,253 patients were included. Over the two periods, the
proportion of patients >=80 years old increased (18.5% vs. 23.1%; p < .0001) as
did the proportion of endovascular repair (EVAR) (44.3% vs. 60.6; p < .0001). In
the latter period, 25.8% of AAAs were less than 5.5 cm. The mean annual volume of
open repairs per centre decreased from 12.9 to 10.6 between the two periods (p <
.0001), and it increased for EVAR from 10.0 to 17.1 (p < .0001). Overall, peri
operative mortality fell from 3.0% to 2.4% (p < .0001). Mortality for EVAR
decreased from 1.5% to 1.1% (p < .0001), but the outcome worsened for open repair
from 3.9% to 4.4% (p = .008). The peri-operative risk was greater for
octogenarians (overall, 3.6% vs. 2.1%, p < .0001; open, 9.5% vs. 3.6%, p < .0001;
EVAR, 1.8% vs. 0.7%, p < .0001), and women (overall, 3.8% vs. 2.2%, p < .0001;
open, 6.0% vs. 4.0%, p < .0001; EVAR, 1.9% vs. 0.9%, p < .0001). Peri-operative
mortality after repair of AAAs <5.5 cm was 4.4% with open repair and 1.0% with
EVAR, p < .0001. CONCLUSIONS: In this large international cohort, total peri
operative mortality continues to fall for the treatment of intact AAAs. The
number of EVAR procedures now exceeds open procedures. Mortality after EVAR has
decreased, but mortality for open operations has increased. The peri-operative
mortality for small AAA treatment, particularly open surgical repair, is still
considerable and should be weighed against the risk of rupture.
PMID- 28416193
TI - LEP rs7799039, LEPR rs1137101, and ADIPOQ rs2241766 and 1501299 Polymorphisms Are
Associated With Obesity and Chemotherapy Response in Mexican Women With Breast
Cancer.
AB - BACKGROUND: Obesity plays a major role in the pathogenesis of breast cancer.
Leptin (LEP) and adiponectin (ADIPOQ) are important in the regulation of adipose
tissue. The response to cancer treatment depends on the histological and
molecular tumor type, clinical stage, and genetic variability that might promote
carcinogenic development. The aim of this study was to investigate the
association between overweight/obesity and polymorphisms in the LEP (rs7799039),
LEP receptor (LEPR; rs1137101), and ADIPOQ genes (rs2241766, rs1501299) with the
response to breast cancer treatment in Mexican women. PATIENTS AND METHODS: A
sample of 177 patients with primary breast cancer (stage I-III) and who received
neoadjuvant therapy were included. Polymorphisms were genotyped and their serum
LEP concentrations (n = 59) were quantified. RESULTS: The patients' median age
was 53.1 years, the frequency of overweight and obesity was 57 and 84 patients,
respectively, 117 were postmenopausal, and 64 of the patients did not respond to
chemotherapy. An association of the LEP rs7799039, LEPR rs1137101, and ADIPOQ
rs1501299 polymorphisms with overweight/obesity was found. The patients who did
not respond to treatment were more frequently obese, at clinical stage III, had
metastases, and high levels of glucose. Moreover, in samples that were positive
for estrogen receptor, higher levels of LEP were found, and in wild type
genotypes for LEP rs7799039 and LEPR rs1137101. CONCLUSION: There was a direct
association between the polymorphisms in LEP rs7799039 and ADIPOQ rs1501299 with
overweight/obesity, and these genotypes affected the response to chemotherapeutic
treatment, suggesting that an obesogenic microenvironment is more favorable for
tumoral progression.
PMID- 28416196
TI - Another statin option in HIV.
PMID- 28416194
TI - Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate
Environments.
AB - Immune cells function in diverse metabolic environments. Tissues with low glucose
and high lactate concentrations, such as the intestinal tract or ischemic
tissues, frequently require immune responses to be more pro-tolerant, avoiding
unwanted reactions against self-antigens or commensal bacteria. T-regulatory
cells (Tregs) maintain peripheral tolerance, but how Tregs function in low
glucose, lactate-rich environments is unknown. We report that the Treg
transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and
glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide
adenine dinucleotide oxidation. These adaptations allow Tregs a metabolic
advantage in low-glucose, lactate-rich environments; they resist lactate-mediated
suppression of T cell function and proliferation. This metabolic phenotype may
explain how Tregs promote peripheral immune tolerance during tissue injury but
also how cancer cells evade immune destruction in the tumor microenvironment.
Understanding Treg metabolism may therefore lead to novel approaches for
selective immune modulation in cancer and autoimmune diseases.
PMID- 28416195
TI - Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia
(INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised,
double-blind, superiority trial.
AB - BACKGROUND: People living with HIV-1 infection are at greater risk for
cardiovascular disease than seronegative adults. Treatment of dyslipidaemia with
statins has been challenging in people with HIV because of an increased potential
for drug interactions due to competing cytochrome P450 metabolism between statins
and commonly used antiretroviral agents. Neither pitavastatin nor pravastatin
depend on cytochrome P450 for primary metabolism. We aimed to assess the safety
and efficacy of pitavastatin versus pravastatin in adults with HIV and
dyslipidaemia. METHODS: In the INTREPID (HIV-infected patieNts and TREatment with
PItavastatin vs pravastatin for Dyslipidemia) randomised, double-blind, active
controlled, phase 4 trial (INTREPID, we recruited adults aged 18-70 years with
controlled HIV (with CD4 counts >200 cells per MUL and HIV-1 RNA <200 copies per
mL) on antiretroviral therapy for at least 6 months and dyslipidaemia (LDL
cholesterol 3.4-5.7 mmol/L and triglycerides <=4.5 mmol/L) from 45 sites in the
USA and Puerto Rico. Patients being treated with darunavir, or who had homozygous
familial hypercholesterolaemia or any condition causing secondary dyslipidaemia,
or a history of statin intolerance, diabetes, or coronary artery disease were not
eligible. We randomly assigned patients (1:1) to pitavastatin 4 mg or pravastatin
40 mg with matching placebos once daily orally for 12 weeks, followed by a 40
week safety extension. Randomisation was stratified by viral hepatitis B or C
coinfection and computer-generated. Investigators, patients, study staff, and
those assessing outcomes were masked to treatment group. The primary endpoint was
percentage change in fasting serum LDL cholesterol from baseline to week 12 and
the primary efficacy analysis was done in the modified intention-to-treat
population. The safety analysis included all patients who took at least one dose
of study medication. This study is registered with ClinicalTrials.gov, number
NCT01301066. FINDINGS: Between Feb 23, 2011, and March 29, 2013, we randomly
assigned 252 patients to the pitavastatin (n=126) or pravastatin group (n=126).
LDL cholesterol reduction was 31.1% with pitavastatin and 20.9% with pravastatin
(least squares mean difference -9.8%, 95% CI -13.8 to -5.9; p<0.0001) at 12
weeks. At week 52, four patients (3%) in the pitavastatin group and six (5%) in
the pravastatin group had virological failure, with no significant difference
between treatments. Both treatments had neutral effects on glucose metabolism
parameters. 85 patients treated with pitavastatin (68%) and 88 patients treated
with pravastatin (70%) reported treatment-emergent adverse events, and these
caused study discontinuation in six patients (5%) versus five patients (4%). No
serious adverse event occurred in more than one participant and none were
treatment-related according to investigator assessment. The most common treatment
emergent adverse events were diarrhoea in the pitavastatin group (n=12, 10%) and
upper respiratory tract infection in the pravastatin group (n=14, 11%). 11
treatment-emergent serious adverse events were noted in seven patients (6%) in
the pitavastatin group (atrial septal defect, chronic obstructive pulmonary
disease, chest pain, diverticulitis, enterovesical fistula, gastroenteritis,
viral gastroenteritis, herpes dermatitis, multiple fractures, respiratory
failure, and transient ischaemic attack) and four events in three patients (2%)
in the pravastatin group (cerebrovascular accident, arteriosclerosis coronary
artery, myocardial infraction, and muscle haemorrhage). In the pravastatin
treatment group, one additional patient discontinued due to an adverse event
(prostate cancer that was diagnosed during the screening period, 42 days before
first dose of study treatment, and therefore was not a treatment-emergent adverse
event). INTERPRETATION: The INTREPID results support guideline recommendations
for pitavastatin as a preferred drug in the treatment of dyslipidaemia in people
with HIV. FUNDING: Kowa Pharmaceuticals America and Eli Lilly and Company.
PMID- 28416197
TI - Pre-exposure prophylaxis is approved in Scotland.
PMID- 28416198
TI - Engineering human renal epithelial cells for transplantation in regenerative
medicine.
AB - Cellular transplantation may treat several human diseases by replacing damaged
cells and/or providing a local source of trophic factors promoting regeneration.
We utilized human renal epithelial cells (hRECs) isolated from cadaveric donors
as a cell model. For efficacious implementation of hRECs for treatment of kidney
diseases, we evaluated a novel encapsulation strategy for immunoisolation of
hRECs and lentiviral transduction of the Green Fluorescent Protein (GFP) as model
gene for genetic engineering of hRECs to secrete desired trophic factors. In
specific, we determined whether encapsulation through conformal coating and/or
GFP transduction of hRECs allowed preservation of cell viability and of their
trophic factor secretion. To that end, we optimized cultures of hRECs and showed
that aggregation in three-dimensional spheroids significantly preserved cell
viability, proliferation, and trophic factor secretion. We also showed that both
wild type and GFP-engineered hRECs could be efficiently encapsulated within
conformal hydrogel coatings through our fluid dynamic platform and that this
resulted in further improvement of cell viability and trophic factors secretion.
Our findings may lay the groundwork for future therapeutics based on
transplantation of genetically engineered human primary cells for treatment of
diseases affecting kidneys and potentially other tissues.
PMID- 28416199
TI - Effect of Atrial Fibrillation on Mortality, Stroke Risk, and Quality-of-Life
Scores in Patients With Heart Failure (from the Outcomes Registry for Better
Informed Treatment of Atrial Fibrillation [ORBIT-AF]).
AB - The degree to which clinical outcomes are worsened in patients with atrial
fibrillation (AF) with heart failure (HF) compared with those without HF is not
well described. This study aimed to determine the impact of HF on clinical
outcomes in patients with AF. We analyzed data from Outcomes Registry for Better
Informed Treatment of Atrial Fibrillation, a national registry of 10,135 patients
with AF to determine associations between HF and left ventricular ejection
fraction (LVEF) and outcomes, including stroke, mortality, and hospitalization
using Cox multivariable modeling. Atrial Fibrillation Effect on Quality-of-Life
Questionnaire (AFEQT) scores between groups were also compared. Overall, 33% (n =
3,203) of patients had HF; of these 33% (n = 985) had LVEF <=40%. Oral
anticoagulation was prescribed more commonly in patients with HF (81% vs 74%).
Compared with patients without HF, those with HF had similar rate of stroke (1.28
vs 0.88 per 100-patient years, hazard ratio [HR] 1.11, confidence interval [CI]
0.83 to 1.48, p = 0.47) but higher mortality (HR 1.69, CI 1.49 to 1.92, p <0.001)
and hospitalization (HR 1.31, CI 1.23 to 1.39, p <0.0001). Patients with LVEF
<=40% had similar stroke risk (HR 1.06, CI 0.67 to 1.67) but higher mortality (HR
2.06, CI 1.74 to 2.44) and hospitalization (HR 1.38, CI 1.25 to 1.51). AFEQT
overall score was significantly lower (76.9 vs 83.3, p <0.0001) in patients with
HF. In conclusion, HF was associated with increased risk of death and
hospitalization and worse quality of life, but similar rates of thromboembolism
regardless of LVEF among patients with AF. These findings highlight the need to
develop therapeutic strategies targeting functional status and survival for
patients with HF and AF.
PMID- 28416200
TI - Comparison of QRS Duration and Associated Cardiovascular Events in American
Indian Men Versus Women (The Strong Heart Study).
AB - Electrocardiographic QRS duration at rest is associated with sudden cardiac death
and death from coronary heart disease in the general population. However, its
relation to cardiovascular events in American Indians, a population with
persistently high cardiovascular disease mortality, is unknown. The relation of
QRS duration to incident cardiovascular disease during 17.2 years of follow-up
was assessed in 1,851 male and female Strong Heart Study participants aged 45 to
74 years without known cardiovascular disease at baseline. Cox regression with
robust standard error estimates was used to determine the association between
quintiles of QRS duration and incident cardiovascular disease in gender
stratified analyses, adjusted for age, systolic blood pressure, hypertension,
antihypertensive medication use, body mass index, current smoking, diabetes,
total cholesterol, high-density lipoprotein cholesterol, and albuminuria. In
women only, QRS duration in the highest quintile (>=105 ms) conferred
significantly higher risk of cardiovascular disease than QRS duration in the
lowest quintile (64 to 84 ms) (hazard ratio 1.6, 95% CI 1.1 to 2.4) likely
because of higher risks of coronary heart disease (hazard ratio 1.8, 95% CI 1.1
to 3.1) and myocardial infarction (hazard ratio 2.1, 95% CI 1.0 to 4.7).
Furthermore, when added to the Strong Heart Study Coronary Heart Disease Risk
Calculator, QRS duration significantly improved prediction of future coronary
heart disease events in women (Net Reclassification Index 0.17, 95% CI 0.06 to
0.47). In conclusion, QRS duration is an independent predictor of cardiovascular
disease in women in the Strong Heart Study cohort and may have value in
estimating risk in populations with similar risk profiles and a high lifetime
incidence of cardiovascular disease.
PMID- 28416201
TI - The impact of the Nurse Faculty Scholars program on schools of nursing.
AB - BACKGROUND: The Robert Wood Johnson Foundation Nurse Faculty Scholars program was
conceptualized as not only promoting the growth and development of early-career
faculty but as enhancing the research infrastructure of scholars' schools of
nursing. PURPOSE: At the completion of the scholars' three years of support,
deans/directors were asked to provide feedback regarding the institutional impact
of the scholars' participation in the program. METHODS: Phone interviews were
conducted on the first five completed cohorts and a six-item questionnaire was
developed to obtain some quantitative data. DISCUSSION: The program was viewed as
having accelerated the scholars' leadership and scholarship, and their influence
within the school/university and regionally/nationally. Deans/directors generally
agreed that the scholars' experience helped build the school's research
portfolio. CONCLUSION: Looking back on how the participating schools of nursing
fared, one can say that the program's institutional expectations were achieved
most of the time. The program helped scholars build their own reputations and
that in turn had consequences for the school's standing as a whole. A number of
components are described that can be replicated singly or in various combinations
by schools/universities interested in adopting aspects of this program.
PMID- 28416202
TI - Presenteeism in nursing: An evolutionary concept analysis.
AB - BACKGROUND: Presenteeism is an emerging concept in nursing that has been linked
to increased health care costs, patient medication errors and falls, and negative
nurse well-being. However, prior work has utilized various definitions and
antecedents. Clarity on the significance, development, and consequences of
presenteeism in nursing is needed. PURPOSE: This concept analysis seeks to
understand the application of presenteeism within nursing workforce literature
and in the broader workforce context. METHOD: Rodgers' evolutionary concept
analysis method was used. DISCUSSION: The proposed definition of presenteeism as
the act of being physically present at work with reduced performance can be
attributed to multiple antecedents. These include nurse health, professional
identity, work-life balance, and work environment. The prevalence of these
antecedents with high rates of presenteeism among nurses and consequences point
to the need for interventions. CONCLUSION: These findings can guide development
of future interventions and policies that address the broader context of factors
leading to presenteeism.
PMID- 28416203
TI - The S4---S5 linker - gearbox of TRP channel gating.
AB - Transient receptor potential (TRP) channels are cation channels which participate
in a wide variety of physiological processes in organisms ranging from fungi to
humans. They fulfill roles in body homeostasis, are sensors for noxious chemicals
and temperature in the mammalian somatosensory system and are activated by light
stimulated phospholipase C activity in Drosophila or by hypertonicity in yeast.
The transmembrane topology of TRP channels is similar to that of voltage-gated
cation channels. TRP proteins assemble as tetramers with each subunit containing
six transmembrane helices (S1-S6) and intracellular N- and C-termini. Here we
focus on the emerging functions of the cytosolic S4-S5 linker on TRP channel
gating. Most of this knowledge comes from pathogenic mutations within the S4-S5
linker that alter TRP channel activities. This knowledge has stimulated forward
genetic approaches to identify additional residues around this region which are
essential for channel gating and is supported, in part, by recent structures
obtained for TRPV1, TRPV2, TRPV6, TRPA1, and TRPP2.
PMID- 28416204
TI - "They must understand we are people": Pregnancy and maternity service use among
signing Deaf women in Cape Town.
AB - BACKGROUND: Women with disabilities are at disproportionate risk for adverse
pregnancy outcomes, however, there is limited information on their pregnancy
histories. This mixed-methods study focuses on signing Deaf women whose access to
health care may be compromised by language barriers related to their disability.
OBJECTIVE: To describe and compare the pregnancy outcomes and maternity service
use of a sample of signing Deaf women of child-bearing age in Cape Town to the
population of the Western Cape of South Africa. METHODS: We interviewed 42 Deaf
women selected by non-probability snowball sampling, using a structured
questionnaire in South African Sign Language in Cape Town in July 2016. RESULTS:
Average parity of the sample was similar to that of the Western Cape population.
Most women had one or two children (74%). Thirty-one percent of women had
experienced a miscarriage and 19% had terminated a pregnancy. Almost all women
(96%) attended at least one antenatal appointment during their pregnancies, and
all deliveries occurred at a health facility. Women primarily relied on writing
to communicate during antenatal visits and labor/delivery. The majority of women
reported communication issues due to limited interpretation services, and some
reported experiencing mistreatment from hospital staff. CONCLUSION: This study
provides novel information on the pregnancy histories of Deaf women. While
maternal service usage was high, the quality of services were inadequate with
reports of linguistic barriers and mistreatment. Findings suggest the need to
improve maternity care for Deaf women through implementing interpretation
services and providing sensitivity training to health care providers.
PMID- 28416206
TI - Reversible Interferon-Induced Pulmonary Arterial Hypertension in a Patient With
Multiple Sclerosis.
PMID- 28416207
TI - Reflections on the Implementation of Low-Dose Computed Tomography Screening in
Individuals at High Risk of Lung Cancer in Spain.
AB - Lung cancer (LC) is a major public health issue. Despite recent advances in
treatment, primary prevention and early diagnosis are key to reducing the
incidence and mortality of this disease. A recent clinical trial demonstrated the
efficacy of selective screening by low-dose computed tomography (LDCT) in
reducing the risk of both lung cancer mortality and all-cause mortality in high
risk individuals. This article contains the reflections of an expert group on the
use of LDCT for early diagnosis of LC in high-risk individuals, and how to
evaluate its implementation in Spain. The expert group was set up by the Spanish
Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of
Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish
Society of Medical Oncology (SEOM).
PMID- 28416205
TI - The link between schizophrenia and substance use disorder: A unifying hypothesis.
AB - Substance use disorders occur commonly in patients with schizophrenia and
dramatically worsen their overall clinical course. While the exact mechanisms
contributing to substance use in schizophrenia are not known, a number of
theories have been put forward to explain the basis of the co-occurrence of these
disorders. We propose here a unifying hypothesis that combines recent evidence
from epidemiological and genetic association studies with brain imaging and pre
clinical studies to provide an updated formulation regarding the basis of
substance use in patients with schizophrenia. We suggest that the genetic
determinants of risk for schizophrenia (especially within neural systems that
contribute to the risk for both psychosis and addiction) make patients vulnerable
to substance use. Since this vulnerability may arise prior to the appearance of
psychotic symptoms, an increased use of substances in adolescence may both
enhance the risk for developing a later substance use disorder, and also serve as
an additional risk factor for the appearance of psychotic symptoms. Future
studies that assess brain circuitry in a prospective longitudinal manner during
adolescence prior to the appearance of psychotic symptoms could shed further
light on the mechanistic underpinnings of these co-occurring disorders while
identifying potential points of intervention for these difficult-to-treat co
occurring disorders.
PMID- 28416208
TI - Fetal and perinatal stem cells in cardiac regeneration: Moving forward to the
paracrine era.
AB - Cardiovascular disease (CD) is a major burden for Western society. Regenerative
medicine has provided encouraging results, yet it has not addressed the focal
defects causing CD and mainly related to the inefficient repair programme of the
heart. In this scenario, stem cells have been broadly investigated and their
paracrine effect proposed as a possible working strategy to boost endogenous
mechanisms of repair and regeneration from within the cardiac tissue. The
scientific community is now focusing on identifying the most effective stem cell
secretome, as the whole of bioactive factors and extracellular vesicles secreted
by stem cells and endowed with regenerative potential. Indeed, the adult stem
cell-paracrine potential for cardiac regeneration have been widely analyzed with
positive outcome. Nevertheless, low yield, invasive sampling and controversial
self-renewal may limit adult stem cell application. On the contrary, fetal and
perinatal stem cells, which can be easily isolated from leftover sample via
prenatal screening during gestation or as clinical waste material after birth,
can offer an ideal alternative. These broadly multipotent immature progenitors
share features with both adult and embryonic stem cells, show high self-renewal,
but they are not tumorigenic neither cause any ethical concern. While fetal and
perinatal stem cells demonstrated to improve cardiac function when injected in
the injured heart, the comprehensive characterization of their secretome for
future applications is still at its infancy. In this review, we will discuss the
paracrine potential of the fetal and perinatal stem cell secretome to provide
cardiac repair and resurge the dormant mechanisms of cardiac regeneration for
future therapy.
PMID- 28416209
TI - [Is the formal quality of multiple choice questions used for continuing medical
education influenced by guidelines for authors provided by the publishing
houses?]
AB - INTRODUCTION: The widespread use of flawed multiple choice questions (MCQs) in
continuing medical education (CME) has been demonstrated in different studies. In
recent years, quality control measures have been established by some German
publishing houses to ensure the quality of MCQs. OBJECTIVES: The purpose of the
present study is to evaluate whether the quality of author's guidelines and the
quality of MCQs correlate and whether the quality of MCQs in CME has improved
following the implementation of quality control measures. MATERIALS AND METHODS:
A set of 720 items from 6 journals was selected for analysis. A list of 10 item
writing flaws provided by Kuhne-Eversmann et al. was modified. The existing
guidelines for authors of the six selected journals were categorized by their
comprehensiveness. RESULTS: There were substantial differences in item quality
with the percentage of flawed items ranging between 34 % and 92 % of all items
published by a journal. One journal showed considerable improvement of item
quality following the implementation of guidelines for authors (61 % flawed items
in 2006 vs. 33% in 2012). The comprehensiveness of the author's guidelines
correlated negatively with the number of item-writing flaws. CONCLUSIONS: The
correlation between the existence of elaborate guidelines for authors and the
absence of item-writing flaws in MCQs suggests that the publication of guidelines
for authors could result in a higher quality of MCQs, even though the review
process might have a major influence.
PMID- 28416210
TI - Development of a continuous motorcycle protection barrier system using computer
simulation and full-scale crash testing.
AB - Road restraint systems are designed to minimize the undesirable effects of
roadside accidents and improve safety of road users. These systems are utilized
at either side or median section of roads to contain and redirect errant
vehicles. Although restraint systems are mainly designed against car, truck and
bus impacts there is an increasing pressure by the motorcycle industry to
incorporate motorcycle protection systems into these systems. In this paper
development details of a new and versatile motorcycle barrier, CMPS, coupled with
an existing vehicle barrier is presented. CMPS is intended to safely contain and
redirect motorcyclists during a collision event. First, crash performance of CMPS
design is evaluated by means of a three dimensional computer simulation program
LS-DYNA. Then full-scale crash tests are used to verify the acceptability of CMPS
design. Crash tests were performed at CSI proving ground facility using a
motorcycle dummy in accordance with prEN 1317-8 specification. Full-scale crash
test results show that CMPS is able to successfully contain and redirect dummy
with minimal injury risk on the dummy. Damage on the barrier is also minimal
proving the robustness of the CMPS design. Based on the test findings and further
review by the authorities the implementation of CMPS was recommended at highway
system.
PMID- 28416211
TI - Phenotypic heterogeneity of human retinal pigment epithelial cells in passaged
cell populations.
AB - Human retinal pigment epithelial (RPE) cells at different population doublings
(PDs) were cultured for 28 days to examine their phenotypic heterogeneity in a
confluent state. In an early population (PD = 2.8), cells showed a cobblestone
like appearance (type I), which gradually became small and tight, and eventually
exhibited dark pigmentation. Some cells showed a dome-like structure (type II),
which detached from the culture surface during culture. With increasing PD, the
cells showed active migration that caused a shift in phenotype from a single
layer of large, flattened cells (type III) to a multiple cell layers (stratified)
with flattened, irregularly shaped cells (type IV). Immunostaining of specific
RPE markers, ZO-1 and Na+/K+-ATPase revealed that cells have markedly decreased
expressions in a late population (PD = 10.1). RPE phenotypes were classified into
four types by measuring the nuclear size and local density. The frequencies of
type I cells decreased with increasing PD value, while the frequencies of type
III and IV cells increased along with the decrease in type I. The frequencies of
type IV cells at PD = 10.1 had increased by 10.3-fold compared with PD = 2.8.
From these results, the nuclear size and local density were proposed as
indicators for understanding phenotypic heterogeneity of RPE cells in the
passaged cell population during cell expansion. It is concluded that the
population doubling level is an important factor to affect the transition of RPE
phenotype and thereby to modulate the quality of cultured cells.
PMID- 28416212
TI - Conversion of vegetable wastes to organic acids in leaching bed reactor:
Performance and bacterial community analysis.
AB - Vegetable wastes (VWs), which contained abundant solid content, were digested in
a leaching bed reactor (LBR). The tested VWs for acidification in the LBR
included cabbage, potato, and tomato vine. The digestion in the LBR was carried
out at the same organic loading rate of 25 g volatile solid (VS) per liter. It
was found that cabbage and potato produced much more volatile fatty acids (VFAs)
than tomato vine, probably because readily degradable components were more
abundant in cabbage and potato. The retention time to digest each feedstock was
different. It took 4, 5, and 8 days for cabbage, potato, and tomato vine to
completely disappear in the reactor, respectively. The profiles of the VFAs
generated from the three VWs were examined. In all cases, the predominant VFAs
were acetic acid and butyric acid, although the relative abundance of individual
VFA varied across the tested leachate samples. The bacterial community
compositions of the leachates were analyzed by high throughput sequencing, and it
was found that the feedstock strongly affected the bacterial community structure
in the acidogenic process. All leachates had distinct bacterial community
structure, although they did share a common set of core communities that included
Proteobacteria, Firmicutes, and Bacteroidetes.
PMID- 28416214
TI - Corrigendum to 'Nothing to (S)cough at: Pulmonary Mycobacterium avium complex
infection' Am J Med. 2017;130(2):153-156.
PMID- 28416213
TI - A prospective study of Rivaroxaban for central venous catheter associated upper
extremity deep vein thrombosis in cancer patients (Catheter 2).
AB - INTRODUCTION: Patients with cancer are at increased risk of thrombosis,
particularly those with central venous catheter (CVC) placement, which may
predispose to the development of upper extremity deep vein thrombosis (UEDVT).
Standard treatment includes low molecular weight heparin (LMWH) or LMWH bridged
to warfarin. The direct oral anticoagulants (DOACs) have become standard of care
for uncomplicated venous thromboembolism (VTE), but research in patients with
cancer is ongoing. OBJECTIVES: To assess rivaroxaban monotherapy in patients with
cancer who develop UEDVT due to CVC for preservation of line function, and safety
outcomes of VTE recurrence, bleeding risk and death. MATERIALS AND METHODS:
Patients >=18years of age with active malignancy and symptomatic proximal UEDVT
with or without pulmonary embolism (PE), associated with a CVC, were eligible.
Treatment included rivaroxaban 15mg oral twice daily for 3weeks, followed by 20mg
oral daily for 9weeks. Patients were followed clinically for 12weeks to assess
for line function, recurrent VTE and bleeding. RESULTS: Seventy patients (47
women) were included, with mean age 54.1years. The most common malignancy was
breast cancer (41%). Preservation of line function was 100% at 12weeks. The risk
of recurrent VTE at 12weeks was 1.43%, with one episode of fatal PE. 9 patients
(12.9%) experienced 11 total bleeding episodes. CONCLUSIONS: Rivaroxaban showed
promise in treating CVC-UEDVT in cancer patients, resulting in preserved line
function. However, bleeding rates and a fatal pulmonary embolism on treatment are
concerning safety outcomes necessitating further study before rivaroxaban can be
recommended.
PMID- 28416215
TI - Stir bar sorptive extraction and liquid chromatography-tandem mass spectrometry
determination of polar and non-polar emerging and priority pollutants in
environmental waters.
AB - An analytical method based on stir bar sorptive extraction (SBSE) was developed
and validated for the determination of environmental concern pollutants in
environmental waters by liquid chromatography-tandem mass spectrometry (LC
MS/MS). Target compounds include six water and oil repellents (perfluorinated
compounds), four preservatives (butylated hydroxytoluene and three parabens), two
plasticizers (bisphenol A and di(2-ethylhexyl)phthalate), seven surfactants (four
linear alkylbenzene sulfonates, nonylphenol and two nonylphenol ethoxylates), a
flame retardant (hexabromocyclododecane), four hormones, fourteen pharmaceutical
compounds, an UV-filter (2-ethylhexyl 4-methoxycinnamate) and nine pesticides. To
achieve the simultaneous extraction of polar and non-polar pollutants two stir
bar coatings were tested, the classic polydimethylsiloxane (PDMS) coating and the
novel ethylene glycol modified silicone (EG-silicone). The best extraction
recoveries were obtained using EG-silicone coating. The effects of sample pH,
volume and ionic strength and extraction time on extraction recoveries were
evaluated. The analytical method was validated for surface water and tap water
samples. The method quantification limits ranged from 7.0ngL-1 to 177ngL-1. The
inter-day precision, expressed as relative standard deviation, was lower than
20%. Accuracy, expressed as relative recovery values, was in the range from 61 to
130%. The method was applied for the determination of the 48 target compounds in
surface and tap water samples.
PMID- 28416216
TI - 3-(Phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole: A fascinating molecular
framework to study the enantioseparation ability of the amylose (3,5
dimethylphenylcarbamate) chiral stationary phase. Part II. Solvophobic effects in
enantiorecognition process.
AB - The enantiomers of five chiral compounds incorporating the 3-(phenyl-4-oxy)-5
phenyl-4,5-dihydro-(1H)-pyrazole scaffold and differing only in the linear alkyl
chain (varying in length from 1 to 5 carbon atoms) linked to the oxygen atom were
directly separated on the amylose (3,5-dimethylphenylcarbamate) based Chiralpak
AD-3 chiral stationary phase. The effects of the mobile phase composition, the
structure of the analytes and temperature on the retention and enantioselectivity
were investigated. It was found that the enantiomeric separations were in all
cases enthalpy-driven and disfavored by entropic term. U-shape curves obtained by
plotting the chromatographic data versus the alcoholic percentage in n-pentane
methanol and n-hexane-ethanol mobile phases highlighted that, at higher alcohol
concentrations, solvophobic interactions were operative in the retention
mechanism. The unusual trend of such curves was linked to the nature of alkyl
chain of the pyrazolines and it was indicative of the solvophobic contribution to
the achievement of a high degree of enantioseparation.
PMID- 28416217
TI - Overcoming "speed limits" in high throughput chromatographic analysis.
AB - The combination of high speed autosampler technology and ultrafast
chromatographic separations enables faster high throughput analysis. With an
injection cycle time of 10.6 s, MISER (Multiple Injection in a Single
Experimental Run) HPLC-MS analysis of a 96 well microplate can be completed in
only 17min. As chromatographic separations in the sub 5s range become
increasingly common, even faster autosamplers will be needed to realize further
speed improvements in high throughput LC-MS analysis. Indeed with proper hardware
sampling approaches, chromatographic analysis of microplates could approach
speeds of spectrophotometric plate readers while maintaining the advantage of
multicomponent detection and monitoring.
PMID- 28416218
TI - Dummy molecularly imprinted microbeads as solid-phase extraction material for
selective determination of phthalate esters in water.
AB - The aim of this study was to investigate the usability of newly synthesized dummy
molecularly imprinted microbeads (DMIMs) as a solid phase extraction (SPE)
material to determine six phthalate esters (PEs) in water by GC-MS analysis.
Diethyl phthalate (DEP) was used as a dummy template to prepare poly(ethylene
glycol dimethacrylate N-methacryloyl-l-tryptophan methyl ester) [PEMATrp)] DMIMs
by using suspension polymerization. The PEMATrp DMIMs were characterized by using
Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy
(XPS) and scanning electron microscopy (SEM). Firstly, the adsorption capacities
of the DMIMs prepared in different template molecule (DEP) to functional monomer
(MATrp) ratios were investigated by using DEP solutions in the concentration
range of 1-500mg/L at pH 3.0. Styrene and vanillic acid were used to evaluate the
selectivity of the prepared DMIMs towards the template molecule (DEP). Then, the
best analytical conditions were investigated for the simultaneous determination
of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP),
benzylbutyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl
phthalate (DnOP) in aqueous media by using the PEMATrp DMIMs as SPE material.
Validation experiments showed that the PEMATrp DMIMs-SPE method had good
linearity at 12.5-250.0MUg/L (0.988-0.999), good precision (1.2-5.9%), and limits
of detection in a range of 0.31-0.41MUg/L.
PMID- 28416219
TI - Displacement of sexual partnerships in trials of sexual behavior interventions: A
model-based assessment of consequences.
AB - We investigated the impact of the displacement of sexual activity from adherent
recipients of an intervention to others within or outside a trial population on
the results from hypothetical trials of different sexual behavior interventions.
A short-term model of HIV-prevention interventions that lead to female rejection
of male partnership requests showed the impact of displacement expected at the
start of a trial. An agent-based model, with sexual mixing and other South
African specific demographics, evaluated consequences of displacement for sexual
behavior interventions targeting young females in South Africa. This model
measured the cumulative incidence among adherent, non-adherent, control and non
enrolled females in a hypothetical trial of HIV prevention. When males made more
than one attempt to seek a partnership, interventions reduced short-term HIV
infection risk among adherent females, but increased it among non-adherent
females as well as controls, non-enrolled (females eligible for the trial but not
chosen to participate) and ineligible females (females that did not qualify for
the trial due to age). The impact of displacement depends on the intervention and
the adherence. In both models, the risk to individuals who are not members of the
adherent intervention group will increase with displacement leading to a biased
calculation for the effect estimates for the trial. Likewise, intent-to-treat
effect estimates become nonlinear functions of the proportion adherent.
PMID- 28416220
TI - Treatment of chronic hepatitis C: can complexity pave the way towards
elimination?
PMID- 28416221
TI - Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously
untreated patients with hepatitis C virus genotype 1b infection without cirrhosis
(GARNET): a single-arm, open-label, phase 3b trial.
AB - BACKGROUND: Clinical studies have shown high rates of sustained virological
response (hepatitis C virus [HCV] RNA <15 IU/mL) at post-treatment week 12
(SVR12) in patients with genotype 1b infection with and without cirrhosis who
received coformulated ombitasvir, paritaprevir, and ritonavir, plus dasabuvir,
without ribavirin, for 12 weeks. In this study, we aimed to assess 8-week
treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without
ribavirin in patients infected with HCV genotype 1b without cirrhosis. METHODS:
We did a multicentre, open-label, single-arm, phase 3b study (GARNET) in 20
hospitals or clinics in Australia, Canada, France, Germany, Israel, Italy, Spain,
and the UK, to assess the safety and efficacy of an 8-week treatment duration of
once-daily oral ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, plus
twice-daily oral dasabuvir 250 mg in previously untreated patients with chronic
HCV genotype 1b infection without cirrhosis (as assessed by liver biopsy,
transient elastography, or serum markers). Eligible patients were aged at least
18 years, with more than 1000 IU/mL HCV RNA, and a laboratory result at screening
indicating infection with HCV genotype 1b subtype only. Patients were excluded if
they had evidence of HCV genotype or subtype other than genotype 1b, if they
tested positive for hepatitis B surface antigen or anti-HIV antibody at
screening, or if they had previously been treated for HCV. The primary endpoint
was the proportion of patients with SVR12; the primary endpoint and safety were
assessed in all patients who received at least one dose of study drugs. This
trial is registered with ClinicalTrials.gov, number NCT02582632. FINDINGS:
Patients were screened between Nov 24, 2015, and March 1, 2016, and 166 patients
were enrolled. 163 (98%) of 166 enrolled patients had HCV genotype 1b infection,
and three (2%) of 166 had other genotypes or subtypes (genotype 1a, genotype 1d,
and genotype 6). All enrolled patients received at least one dose of study drugs.
162 (98% [95% CI 95.3-99.9]) of 166 patients achieved SVR12. One patient
discontinued treatment on day 45 due to adverse events. Most adverse events were
mild in severity, and the most common adverse events were headache (35 [21%] of
166) and fatigue (28 [17%] of 166). Two (1%) of 166 patients had serious adverse
events; neither were considered related to study drug treatment. INTERPRETATION:
Treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without
ribavirin, for 8 weeks was efficacious and well tolerated. 8-week treatment
options for previously untreated patients with HCV genotype 1b infection without
cirrhosis are limited; shortening the treatment duration might reduce the burden
associated with medical visits and procedures, thereby improving access to care
and enabling the treatment of more patients. FUNDING: AbbVie.
PMID- 28416223
TI - Study on emission of hazardous trace elements in a 350 MW coal-fired power plant.
Part 2. arsenic, chromium, barium, manganese, lead.
AB - Hazardous Trace elements (HTEs) emitted from coal combustion has raised
widespread concern. Studies on the emission characteristics of five HTEs, namely
arsenic (As), chromium (Cr), barium (Ba), manganese (Mn), lead (Pb) at three
different loads (100%, 83%, 71% output) and different coal types were performed
on a 350 MW coal-fired power plant equipped with SCR, ESP + FF, and WFGD. HTEs in
the flue gas at the inlet/outlet of each air pollution control device (APCD) were
sampled simultaneously based on US EPA Method 29. During flue gas HTEs sampling,
coal, bottom ash, fly ash captured by ESP + FF, fresh desulfurization slurry,
desulfurization wastewater were also collected. Results show that mass balance
rate for the system and each APCD is in an acceptable range. The five studied
HTEs mainly distribute in bottom and ESP + FF ash. ESP + FF have high removal
efficiency of 99.75-99.95%. WFGD can remove part of HTEs further. Total removal
rate across the APCDs ranges from 99.84 to 99.99%. Concentration of HTEs emitted
to atmosphere is within the extremely low scope of 0.11-4.93 MUg/m3. Emission
factor of the five studied HTEs is 0.04-1.54 g/1012J. Content of As, Pb, Ba, Cr
in solid samples follows the order of ESP + FF ash > bottom ash > gypsum. More
focus should be placed on Mn in desulfuration wastewater, content of which is
more than the standard value. This work is meaningful for the prediction and
removal of HTEs emitted from coal-fired power plants.
PMID- 28416222
TI - Dentin on the nanoscale: Hierarchical organization, mechanical behavior and
bioinspired engineering.
AB - OBJECTIVE: Knowledge of the structural organization and mechanical properties of
dentin has expanded considerably during the past two decades, especially on a
nanometer scale. In this paper, we review the recent literature on the
nanostructural and nanomechanical properties of dentin, with special emphasis in
its hierarchical organization. METHODS: We give particular attention to the
recent literature concerning the structural and mechanical influence of collagen
intrafibrillar and extrafibrillar mineral in healthy and remineralized tissues.
The multilevel hierarchical structure of collagen, and the participation of non
collagenous proteins and proteoglycans in healthy and diseased dentin are also
discussed. Furthermore, we provide a forward-looking perspective of emerging
topics in biomaterials sciences, such as bioinspired materials design and
fabrication, 3D bioprinting and microfabrication, and briefly discuss recent
developments on the emerging field of organs-on-a-chip. RESULTS: The existing
literature suggests that both the inorganic and organic nanostructural components
of the dentin matrix play a critical role in various mechanisms that influence
tissue properties. SIGNIFICANCE: An in-depth understanding of such nanostructural
and nanomechanical mechanisms can have a direct impact in our ability to evaluate
and predict the efficacy of dental materials. This knowledge will pave the way
for the development of improved dental materials and treatment strategies.
CONCLUSIONS: Development of future dental materials should take into
consideration the intricate hierarchical organization of dentin, and pay
particular attention to their complex interaction with the dentin matrix on a
nanometer scale.
PMID- 28416224
TI - Post-discharge kidney function is associated with subsequent ten-year renal
progression risk among survivors of acute kidney injury.
AB - The extent to which renal progression after acute kidney injury (AKI) arises from
an initial step drop in kidney function (incomplete recovery), or from a long
term trajectory of subsequent decline, is unclear. This makes it challenging to
plan or time post-discharge follow-up. This study of 14651 hospital survivors in
2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent
renal decline by using the post-discharge estimated glomerular filtration rate
(eGFR) rather than the pre-admission as a new reference point for determining
subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo
CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death
was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4
(4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline
was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs
no AKI) was greatest among those with higher post-discharge eGFRs with
multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68
1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30,
respectively. The excess risk after AKI persisted over ten years of study,
irrespective of AKI severity, or post-episode proteinuria. Thus, even if post
discharge kidney function returns to normal, hospital admission with AKI is
associated with increased renal progression that persists for up to ten years.
Follow-up plans should avoid false reassurance when eGFR after AKI returns to
normal.
PMID- 28416227
TI - Association between current smoking and cognitive impairment depends on age: A
cross-sectional study in Xi'an, China.
AB - BACKGROUND: Cigarette smoking is a modifiable risk factor for cognitive
impairment, while the relationship between current smoking and cognitive
impairment is not fully understood. The objectives were to identify a possible
association between current smoking and cognitive impairment depending on age in
the Chinese rural population. METHODS: Data for the study consisted of 1,782
participants (40 years and older) who lived in a rural village in the vicinity of
Xi'an, China. Data about smoking history and cognitive function were collected.
Cognitive function was scored by the Mini-Mental State Examination. The effect of
age on the relationship between current smoking and cognitive impairment was
analyzed with interaction and stratified analysis by logistic regression models.
RESULTS: Interaction analysis showed that current smoking is positively related
with cognitive impairment (odds ratio [OR]=9.067; 95% confidence interval [95%
CI] 1.305-62.979; P=.026). However, the interaction term, age by current smoking,
is negatively related with cognitive impairment (OR=0.969; 95%CI 0.939-0.999;
P=.045). Stratified logistic regression showed that in the 40-65 years of age
sublayer, OR of current smoking is 1.966 (P=.044), whereas in the>65 years of age
sublayer, the OR is 0.470 (P=.130). This means that the association between
current smoking and cognitive impairment with age might be positive (OR>1) in
lower age sublayers, but no significant difference in higher age sublayers.
CONCLUSIONS: In conclusion, current smoking might be positively associated with
cognitive impairment in the middle-aged but the relationship declines with
increasing age.
PMID- 28416228
TI - Cat scratch disease. Onset as epithroclear tumor.
PMID- 28416226
TI - Klotho restoration via acetylation of Peroxisome Proliferation-Activated Receptor
gamma reduces the progression of chronic kidney disease.
AB - Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho
expression closely correlates with the development and progression of chronic
kidney disease (CKD). Klotho is also a downstream gene of Peroxisome
Proliferation-Activated Receptor gamma (PPARgamma), a major transcription factor
whose functions are significantly affected by post-translational modifications
including acetylation. However, whether PPARgamma acetylation regulates renal
Klotho expression and function in CKD is unknown. Here we test whether renal
damage and reduced Klotho expression in the adenine CKD mouse model can be
attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A. This
inhibition up-regulated Klotho mainly through an enhancement of PPARgamma
acetylation, stimulation of PPARgamma binding to Klotho promoter, and PPARgamma
dependent increase in Klotho transcription, with a substantial control of the
regulation occurring via PPARgamma acetylations on K240 and K265. Consistently
trichostatin A-induced reversal of Klotho loss and renoprotective effects were
abrogated in PPARgamma knockout mice, supporting that PPARgamma is an essential
acetylation target for Klotho restoration and renal protection. Intriguingly, the
kidneys of adenine-fed CKD mice displayed deregulated HDAC3 up-regulation.
Selective HDAC3 inhibition effectively alleviated Klotho loss and kidney injury,
whereas the protective effects were largely abolished when Klotho was knocked
down by siRNA, suggesting that aberrant HDAC3 and Klotho loss are crucial
components involved in the renal damage of mice with CKD. Our study identified an
important signaling cascade and key components contributing to the pathogenesis
of CKD. Thus, targeting Klotho loss by HDAC3 inhibition has promising therapeutic
potential for the reduction of CKD progression.
PMID- 28416225
TI - B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic
disease in a rat model of polycystic kidney disease.
AB - Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion
and fibrosis, frequently leading to end-stage renal disease. Increased
vasopressin and cAMP signaling, dysregulated calcium homeostasis, and
hypertension play major roles in PKD progression. The guanylyl cyclase A agonist,
B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti
hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD
pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on
PKD progression in a rat model of PKD. Sustained BNP production significantly
reduced kidney weight, renal cystic indexes and fibrosis, in concert with
suppressed hepatic cystogenesis in vivo. In vitro, BNP decreased cystic
epithelial cell proliferation, suppressed fibrotic gene expression, and increased
intracellular calcium. Together, our data demonstrate multifaceted effects of
sustained activation of guanylyl cyclase A on polycystic kidney and liver
disease. Thus, targeting the guanylyl cyclase A-cGMP axis may provide a novel
therapeutic strategy for hepatorenal fibrocystic diseases.
PMID- 28416229
TI - Recurrent laryngeal nerve paralysis in a lung cancer patient: A cause of
contralateral vocal cord hypermetabolism on PET/CT.
PMID- 28416230
TI - Porphyria cutanea tarda in a patient with hepatitis C.
PMID- 28416231
TI - Unilateral neuroretinitis.
PMID- 28416232
TI - Experience in real clinical practice with new direct acting antivirals in chronic
hepatitis C.
AB - INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical
practice in patients with chronic HCV (CHC) has been a milestone in medicine.
PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with
chronic HCV treated with direct-acting antivirals. Efficacy and safety of
treatment and factors associated with failure treatment were evaluated. RESULTS:
Age 54+/-10. Male (70%). Cirrhosis (60%). Distribution according to genotypes:
G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naive (56%).
SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best
cure rates were achieved with a 3D/2D+/-ribavirin (SVR=97.4%;n=39) and
sofosbuvir/ledipasvir+/-ribavirin (RVS=93.1%; n=29) combination. An SVR rate of
<90% was achieved with sofosbuvir+simeprevir+/-ribavirin (SVR=88%, n=25),
simeprevir+daclatasvir+/-ribavirin 73%, n=15). The association of ribavirin to
these last three therapeutic options (n=19) improved cure rates (SVR=94.7%,
18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output
transplant list (20%). Substitutions associated with resistors NS3: G1a
(positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a
(position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with
failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin
dosage<600mg/day. DISCUSSION: The presence of genotype 3, ascites or dosage of
ribavirin<600mg/day were associated with higher failure rates. The use of
ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with
sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance
test is available.
PMID- 28416233
TI - Multiple syphilitic chancre.
PMID- 28416234
TI - Orbit lymphomas in Spanish population. Descriptive study and side effects of
treatment with radiotherapy.
PMID- 28416235
TI - Supplementation of vitamin D and reduction of analgesic requirements in
institutionalized elderly with chronic musuloskeletal pain.
PMID- 28416236
TI - Cardiac tamponade. A complication of treatment with infliximab.
PMID- 28416237
TI - Proliferative verrucous leukoplakia of the tongue.
PMID- 28416238
TI - Pulmonary involvement in alveolar echinococcosis.
PMID- 28416239
TI - Postprandial hypoglycemia as the only manifestation of insulinoma: exceptional
case report.
PMID- 28416240
TI - Efficacy of tumour necrosis factor antagonists in stricturing Crohn's disease: A
tertiary center real-life experience.
AB - BACKGROUND: Stenosis is the most common complication of Crohn's disease (CD).
Long-term outcome of patients receiving tumour necrosis factor (TNF) antagonists
for such disease complication is poorly understood. METHODS: 51 CD patients (from
July 2006 to November 2015) who had a diagnosis of small bowel or colonic
stenosis, diagnosed by colonoscopy and/or MRI enterography, and were treated with
TNF antagonists (adalimumab or infliximab) were enrolled. The primary outcome was
to assess the rate of success of TNF antagonists on avoiding abdominal surgery
for stricturing CD patients. RESULTS: 20 patients (39.2%) underwent surgery
during the follow-up period. The overall incidence of abdominal surgery was 1.8
per 100 person-months at risk, while the median time to surgery was 37.9 months.
The univariable and multivariable Cox's proportional hazards analysis of baseline
parameters indicated that disease location (colonic vs ileal, HR: 28.2, 95% CI:
2.45-324, p=0.007; ileocolonic vs ileal, HR: 3.38, 95% CI: 1.09-10.5, p=0.035),
prestenotic dilatation (per 1-mm increase, HR: 1.08, 95% CI: 1.01-1.15, p=0.022)
and the existence of non-perianal fistula (HR: 9.77, 95% CI: 2.99-31.9, p<0.001)
are independent risk factors for abdominal surgery. CONCLUSIONS: In stricturing
CD, anti-TNFs are effective in up to about two-thirds of the patients.
PMID- 28416241
TI - Circulating tumor DNA-From bench to bedside.
AB - In the era of personalized medicine, tumor sampling is paramount to enable the
assessment of actionable molecular aberrations to help rationalize and guide
treatment decisions. Longitudinal tracking of such aberrations may also be
helpful to detect emerging drug resistance and to allow for timely modifications
to ongoing therapies to improve patient outcomes. Nevertheless, tumor tissue
sampling involves an invasive procedure with potential risks to patients and
involves logistical challenges. As such, other less invasive and safer methods
such as blood sampling for molecular profiling has been gaining traction. In this
article, we discuss the concept of circulating tumor DNA, the technology
platforms available for its interrogation, and its current applications in the
clinic. We also envision how circulating tumor DNA may be applied at multiple
time points along a patient's cancer journey to guide diagnosis, prognostication,
and therapeutic decisions.
PMID- 28416242
TI - Human papillomavirus and oral squamous cell carcinoma: A review of HPV-positive
oral squamous cell carcinoma and possible strategies for future.
AB - Oral squamous cell carcinoma (OSCC) is a common cancer worldwide. Besides tobacco
use and alcohol consumption, human papillomavirus (HPV) infection has also been
identified as a risk factor for OSCC recently. The OSCC incidence has increased
in recent years, especially among younger women. The purpose of this article is
to review clinical and epidemiological studies on the association between HPV
infection and OSCCs, and the efficacy of HPV vaccine, so as to provide possible
policy implications for preventing HPV-positive OSCC. It is necessary to review
the present related body of knowledge to determine whether the association
between HPV infection and OSCC has been thoroughly studied. The study was based
on literature review. Studies were identified using electronic databases
including MEDLINE, PubMed, EMBASE, etc. The inclusion and exclusion criteria were
based on consultation from a panel of experts in this area and carefully
designed. Based on a systematic review of literatures, HPV infection is a
possible cause for the incidence of HPV-positive OSCCs. The prevalence of HPV
infection possibly contributed to the increasing trends of HPV-positive OSCCs.
Oral HPV infection is a form of HPV transmission. Oral sex behaviors and open
mouthed kissing are probably reasons for oral HPV infection. We also have some
epidemiological evidences proving that HPV vaccine provides a possible solution
for preventing oral HPV infection. Increased awareness of HPV-positive OSCCs is
essential due to the severity of this problem. Biological and epidemiological
data regarding the link between sexual behavior and HPV-associated cancers
indicate a probable connection, although definitive data are needed. Future
studies are needed to investigate the mechanisms of how HPV infection causes HPV
positive OSCCs, whether HPV vaccine provides a prevention for OSCCs, and other
important issues.
PMID- 28416243
TI - Psychological Interventions for Children with Functional Somatic Symptoms: A
Systematic Review and Meta-Analysis.
AB - OBJECTIVE: To analyze the effectiveness of psychological treatments on symptom
load and associated disability in children with functional somatic symptoms, and
to explore potential moderators of effects. STUDY DESIGN: Cochrane, PubMed,
PsycINFO, EMBASE, and CINAHL were searched for randomized controlled trials
published in peer-reviewed journals. Randomized controlled trials studying the
effect of a psychological treatment on symptom load and disability in children
with functional somatic symptoms were selected. Data on symptom load, disability,
and school absence directly post-treatment and at follow-up were extracted by 2
assessors. Studies were appraised with the Cochrane risk of bias tool.
Standardized mean differences were pooled in a random-effects model.
Heterogeneity in effect-sizes was explored by use of meta-regressions. PROSPERO
Registration ID: CRD42015029667. RESULTS: Out of 4098 identified records, 27
studies were included in this review of which 21 were included in meta-analyses.
Psychological treatments reduced symptom load (Hedges g = -0.61), disability
(Hedges g = -0.42), and school absence (Hedges g = -0.51) post-treatment in
children suffering from various functional somatic symptoms. Effects were
maintained at follow-up. Type and duration of symptoms, age, and treatment dose
did not explain heterogeneity in effect-sizes between studies. Effect-sizes
should be interpreted with caution because of the variety in outcome measures,
unexplained heterogeneity in found effects and potential publication bias.
CONCLUSIONS: Psychological interventions reduce symptom load, disability, and
school absence in children with functional somatic symptoms. Future research
should clarify which patient and treatment characteristics modify outcomes.
PMID- 28416244
TI - Response to comment on: Upper gastrointestinal endoscopy is safe and feasible in
the early postoperative period after Roux-en-Y gastric bypass.
PMID- 28416245
TI - A simple and efficient method for CRISPR/Cas9-induced mutant screening.
AB - The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated protein 9 (Cas9) system provides a technological breakthrough in
mutant generation. Several methods such as the polymerase chain reaction
(PCR)/restriction enzyme (RE) assay, T7 endonuclease I (T7EI) assay, Surveyor
nuclease assay, PAGE-based genotyping assay, and high-resolution melting (HRM)
analysis-based assay have been developed for screening CRISPR/Cas9-induced
mutants. However, these methods are time- and labour-intensive and may also be
sequence-limited or require very expensive equipment. Here, we described a cost
effective and sensitive screening technique based on conventional PCR, annealing
at critical temperature PCR (ACT-PCR), for identifying mutants. ACT-PCR requires
only a single PCR step followed by agarose gel electrophoresis. We demonstrated
that ACT-PCR accurately distinguished CRISPR/Cas9-induced mutants from wild type
in both rice and zebrafish. Moreover, the method can be adapted for accurately
determining mutation frequency in cultured cells. The simplicity of ACT-PCR makes
it particularly suitable for rapid, large-scale screening of CRISPR/Cas9-induced
mutants in both plants and animals.
PMID- 28416246
TI - Leg movements during sleep and respiratory events are not causally linked.
PMID- 28416247
TI - Adaptive CRT in patients with normal AV conduction and left bundle branch block:
Does QRS duration matter?
AB - BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is a dynamic
optimization algorithm which paces only the left ventricle (LV) when atrio
ventricular (AV) conduction is normal, thus reducing right ventricular (RV)
pacing. However, the impact of QRS duration on aCRT efficacy remains uncertain.
We examined whether QRS duration impacts aCRT effectiveness in patients with left
bundle branch block (LBBB) and preserved AV conduction. METHODS: Randomized
patients in the Adaptive CRT trial, which enrolled NYHA III/IV patients, were
used in this analysis. Patients were randomized to receive aCRT or echo-optimized
bi-ventricular CRT (control arm). Endpoints for this analysis were clinical
composite score (CCS) at 6months post-implant and time to first heart failure
(HF) hospitalization or death. RESULTS: Among the 199 patients with LBBB and
normal AV intervals at baseline, 80 patients (40%) had a baseline moderately wide
QRS of 120-150ms. In this subgroup, a greater proportion of aCRT patients had an
improved CCS (79% vs. 50%) at 6months compared to the control group (p=0.03).
There was also a trend toward a lower risk of death or HF hospitalization (hazard
ratio: 0.53; 95% CI: 0.24-1.15; p=0.10) in the moderately wide QRS subgroup with
aCRT compared to the control arm. In the wide QRS subgroup, the efficacy was
comparable in both treatment arms. CONCLUSION: Adaptive CRT was associated with
improved patient outcomes over echo-optimized bi-ventricular CRT in patients with
preserved AV conduction, LBBB, and moderately wide QRS. The adaptive cardiac
resynchronization therapy trial (ClinicalTrials.gov Identifier: NCT00980057) was
sponsored by Medtronic plc, Mounds View, MN.
PMID- 28416249
TI - Prognostic accuracy of clinical signs and diagnostic tests in cow's milk allergy
in newborns.
AB - BACKGROUND: The aim of the study was to explore the correlation between clinical
signs and confirmatory tests for cow's milk allergy (CMA) in the neonatal period
and their relation to family history and the occurrence of food allergies in the
postneonatal period. METHODS: The medical documentation of 361 newborns with
suspected CMA and exclusion of other comorbidities was analyzed. The correlations
between clinical signs and methods to confirm CMA [elevated levels of total
immunoglobulin E (IgE) and/or specific IgE for cow's milk, improvement after the
introduction of a cow's milk-free diet and positive challenge procedure] were
studied. In 90 children, the data were additionally analyzed in relation to
outcome (at the age of 1-11 years), evaluated by questionnaires, which inquired
about signs and symptoms of food allergy, methods of CMA confirmation, and the
presence of other food allergies. RESULTS: There was a positive correlation
between exanthema and confirmed CMA in the neonatal period (R = 0.184; p =
<0.001; n = 361), and hematochezia and confirmed CMA in the neonatal (R = 0.203;
p < 0.001; n = 361) and postneonatal period (R = 0.215; p = 0.042; n = 90).
Additional food allergies in the postneonatal period were positively correlated
with neonatal CMA (R = 0.275; p = 0.009; n = 90). No correlation was found
between a positive family history of food allergies and CMA in the neonatal (R =
0.66; p = 0.398; n = 165) and postneonatal periods (R = 0.00; p = 1.000; n =
116). CONCLUSION: Neonatal exanthema and hematochezia were the predominant
clinical signs in neonates with CMA. Allergies to other food allergens appeared
more frequently in children with CMA in the neonatal period. Neonatal CMA did not
occur more frequently in families with food allergies.
PMID- 28416248
TI - Contemporary practice and outcomes of an elderly cohort of Japanese patients with
non-ST-elevation acute coronary syndrome in the era of routine early invasive
strategy.
AB - BACKGROUND: An early invasive strategy for patients with non-ST-segment elevation
acute coronary syndrome (NSTE-ACS) has been recommended. However, patients at
greater risk including the elderly are more often managed conservatively. We
aimed to elucidate contemporary practice and outcomes of patients with NSTE-ACS
who were referred to our hospital located in Kitakyushu City, one of the most
aging metropolises in Japan. METHODS: A total of 270 consecutive NSTE-ACS
patients hospitalized between January 2012 and December 2014 were retrospectively
studied. RESULTS: Median [interquartile range] age was 73 [64, 80]years. Coronary
angiography was performed in 264 (98%) patients. Importantly, 75% and 89%
underwent angiography within 24h and 72h after admission, respectively.
Revascularization was done in 124 (79%). The all-cause, in-hospital mortality was
3.7% and was higher in patients aged >=80years (8.5% vs. 2.0% in those aged
<80years, p<0.0001). No patient developed major bleeding or stroke during
hospitalization. Killip class IV at presentation (odds ratio [OR] 8.77, 95%
confidence intervals [CI] 1.64-47.6) and left main trunk disease (OR 7.58, 95% CI
1.28-45.5) were independently associated with in-hospital death. These two
variables and a high (>=140) GRACE score were associated with a higher 1-year
mortality by Kaplan-Meier survival analysis (p<0.0001). CONCLUSIONS: An early
invasive strategy was safely done in an elderly cohort of Japanese patients with
NSTE-ACS. In addition to early invasive approach, a further therapeutic strategy,
most probably targeting a shock status, is needed to improve both short- and long
term survival.
PMID- 28416250
TI - Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy.
AB - Therapeutic hypothermia (TH) is a recommended regimen for newborn infants who are
at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy
(HIE). The Task Force of the Taiwan Child Neurology Society and the Taiwan
Society of Neonatology held a joint meeting in 2015 to establish recommendations
for using TH on newborn patients with HIE. Based on current evidence and experts'
experiences, this review article summarizes the key points and recommendations
regarding TH for newborns with HIE, including: (1) selection criteria for TH; (2)
choices of method and equipment for TH; (3) TH prior to and during transport; (4)
methods for temperature maintenance, monitoring, and rewarming; (5) systemic care
of patients during TH, including the care of respiratory and cardiovascular
systems, management of fluids, electrolytes, and nutrition, as well as sedation
and drug metabolism; (6) monitoring and management of seizures; (7) neuroimaging,
prognostic factors, and outcomes; and (8) adjuvant therapy for TH.
PMID- 28416251
TI - Initial Asthma Severity Assessment Tools as Predictors of Hospitalization.
AB - BACKGROUND: Assessment tools to classify and prioritize patients, such as systems
of triage, and indicators of severity, such as clinical respiratory scores, are
helpful in guiding the flow of asthmatic patients in the emergency department.
OBJECTIVE: Our aim was to assess the performance of the Pediatric Assessment
Triangle (PAT), triage level (TL), Pulmonary Score (PS), and initial O2
saturation (O2 sat), in predicting hospitalization in pediatric acute asthma
exacerbations. STUDY DESIGN: Retrospective study evaluating PAT, TL, and PS at
presentation, and initial O2 sat of asthmatic children in the pediatric emergency
department (PED). The primary outcome measure was the rate of hospitalization.
Secondary outcomes were length of stay (LOS) in the PED and admission to the
pediatric intensive care unit (PICU). RESULTS: PAT, TL, PS, and initial O2 sat
were recorded in 14,953 asthmatic children. Multivariate analysis yielded the
following results: Abnormal PAT and more severe TLs (I-II) were independent risk
factors for hospitalization (odds ratio [OR] 1.6, 95% confidence interval [CI]
1.4-1.8; OR 3.4, 95% CI 2.6-4.3, respectively) and longer LOS (OR 1.5, 95% CI 1.3
1.7; OR 2.6, 95% CI 2-3.3, respectively). PS > 3 showed a strong association with
hospitalization (OR 8.1, 95% CI 7-9.4), PICU admission (OR 9.6, 95% CI 3-30.9)
and longer LOS (OR 6.2, 95% CI 5.6-6.9). O2 sat < 94% was an independent
predictor of admission (OR 5.2, 95% CI 4.6-5.9), PICU admission (OR 4.6, 95% CI
4.5-4.6), and longer LOS (OR 4.6, 95% CI 4.1-5.2). CONCLUSIONS: PAT, TL, PS, and
initial O2 sat are good predictors of hospitalization in pediatric acute asthma
exacerbations.
PMID- 28416252
TI - Hydroceles-Not Just For Men.
AB - BACKGROUND: Hydroceles develop in females through the canal of Nuck. This canal
is formed when the processes vaginalis fails to obliterate during development.
The canal of Nuck can lead to the formation of not only hydroceles, but hernias
as well. Although physicians typically think of hydroceles occurring in males, on
rare occasions, they do occur in females because of this defect. They are often
mistaken for incarcerated hernias, making ultrasound an excellent tool to
distinguish between them and guide further treatment. CASE REPORT: We report a
rare case of a 46-year-old female with the chief complaint of a painful groin
mass. A diagnosis of a hydrocele was made by point of care ultrasonography in the
emergency department after being misdiagnosed by computed tomography scan on two
previous occasions. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Point of
care ultrasound (POCUS) is a valuable tool for emergency physicians and can lead
to quick diagnoses and appropriate management of the patient. Using ultrasound in
conjunction with other imaging modalities can improve diagnostic accuracy. POCUS
is portable and a powerful tool for immediate answers, and continues to prove its
utility for clinical decision making.
PMID- 28416253
TI - Mechanical Stability of the Taper Connection of Large Metal Femoral Heads With
Adapter Sleeves in Total Hip Arthroplasty Analyzed Using Explicit Finite Element
Simulations.
AB - BACKGROUND: Large diameter heads (LDHs) of metal-on-metal bearings in total hip
arthroplasty provide increased range of motion and reduced dislocation rates.
However, major concerns grew over high wear rates from the modular connection
between femoral stem and head, especially in combination with adapter sleeves.
METHODS: A computational study on the taper connection stability of LDH (50 mm)
with adapter sleeves of different lengths (S, M, L, and XL) compared with a
standard femoral head (32 mm) without adapter sleeves was conducted using
explicit finite element analyses. Four different impact configurations were
considered resulting from varied mallet mass (0.5 vs 1.0 kg) and velocity (1.0 vs
2.0 m/s). The taper stability was evaluated by determination of the pull-off
forces and micromotions due to simulated joint loads during walking (2 kN and 7.9
Nm, respectively). Moreover, the deformations of the adapter sleeves and the
contact area in the taper connections were evaluated. RESULTS: Although the pull
off forces of the LDH with different-sized adapter sleeves were comparable,
contact area decreased and adapter sleeve deformations increased (up to 283%)
with an increasing adapter sleeve length. Moreover, the micromotions of LDH with
adapter sleeves were up to 7-times higher, as compared with the standard femoral
head without an adapter sleeve. CONCLUSION: The present numerical study confirms
that the assembly technique of LDH with adapter sleeves reveals increased
micromotions compared with standard femoral head sizes. We could demonstrate that
deviations of the stem trunnion geometry and improper surgical instructions led
to worse mechanical stability of the taper connection.
PMID- 28416254
TI - Non-critical urinary cadmium excretion as a risk factor associated with tubular
markers of early kidney injury in Central Mexico.
PMID- 28416255
TI - Differences between 2nd and 3rd generation seric parathormone determination
methods on mortality in haemodialysis patients.
AB - : Parathormone plays a key role in controlling mineral metabolism. PTH is
considered a uremic toxin causing cardiovascular damage and cardiovascular
mortality in dialysis patients. There are two different assays to measure PTH
called 2nd generation or intact PTH (iPTH) and 3rd generation or bioPTH (PTHbio).
OBJECTIVE: To evaluate the differences in mortality of dialysis patients between
both assays to measure PTH, as well as the possible prognostic role of the
PTHbio/iPTH ratio. METHODS: 145 haemodialysis patients were included with 2-year
monitoring including baseline laboratory test and annually thereafter. RESULTS:
21 patients died in the first year and 28 in the second. No correlation was found
between PTH, PTHbio and PTHbio/iPTH ratio with mortality. Both PTH have a perfect
correlation between them and correlate similarly with other molecules of the
mineral metabolism. The extreme baseline values of PTH are those of higher
mortality. In survival by iPTH intervals (according to guidelines and COSMOS
study), a J curve is observed. When iPTH increases, the ratio decreases, possibly
when increasing fragments no. 1-84. There is no greater prognostic approximation
on mortality with PTHbio than PTHi. There was also no difference in mortality
when progression ratio PTHbio/PTHi was analysed. CONCLUSIONS: We didn't find any
advantages to using bioPTH vs. PTHi as a marker of mortality. BioPTH limits of
normality must be reevaluated because its relationship with iPTH is not
consistent. Not knowing these limits affects its prognostic value.
PMID- 28416256
TI - Youth psychological distress and intermediary markers of risk for CVD: The
emerging field of pediatric psychocardiology.
PMID- 28416257
TI - Nrf2 and regulation of the antioxidant system in the Antarctic silverfish,
Pleuragramma antarctica: Adaptation to environmental changes of pro-oxidant
pressure.
AB - Despite the key importance of Nrf2-Keap1 in regulating antioxidant system in
vertebrates, this system is still poorly investigated in marine species. The
present study focused on the Antarctic silverfish Pleuragramma antarctica which,
during the final phases of embryo development in platelet ice, is challenged by a
sudden enhancement of environmental oxidative conditions associated to ice
melting. Partial coding sequences were identified for Nrf2, its repressor Keap1
and for typical Nrf2-target antioxidant genes, like catalase, glutathione
peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase. Compared to
temperate homologues, the protein sequences showed an elevated conservation of
amino acids essential for catalytic functions, while a few specific substitutions
in non-essential regions may represent a molecular adaptation to improve
flexibility and accessibility to active site at cold temperatures. The role of
the Nrf2-Keap1 pathway in modulating the activation of antioxidant defences was
demonstrated at both transcriptional and functional levels with a clear temporal
increase of antioxidant protection in embryos before the hatching. Such findings
confirm the importance of Nrf2 and highlight regulation of antioxidants as an
adaptive strategy in P. antarctica to protect the early life stages toward the
environmental changes of pro-oxidant pressure.
PMID- 28416258
TI - [Description of 3 cases of skin and soft tissue infections caused by
Streptococcus pneumoniae].
AB - The role of Streptococcus pneumoniae as a causative agent of skin and soft tissue
infections (SSTI) is unusual and its clinical interpretation is difficult. We
describe here three cases of SSTI due to S. pneumoniae in patients admitted to
the Provincial Pediatric Hospital of Misiones, Argentina that were detected
during 10 years of invasive disease (ID) surveillance documented in 2010, 2011
and 2015. These cases involved two girls aged 8 and 7 months old, and a two-year
old male child with diagnoses of gluteal abscess, preseptal cellulites and
pyoderma respectively. All the patients were eutrophic and in good general
condition on admission; one of them was seropositive for HIV. Antimicrobial
susceptibility and serotypes were framed within the local epidemiology of
invasive pneumococcal disease. Despite its low frequency, S. pneumoniae as an
etiological agent of SSTI must be considered. Our findings revalue the role of
the diagnostic laboratory and contribute to document the behavior of this
pathogen.
PMID- 28416259
TI - Parenteral glutamine should not be routinely used in adult critically ill
patients.
PMID- 28416260
TI - Late Genitourinary Toxicity Outcomes in 300 Prostate Cancer Patients Treated With
Dose-escalated Image-guided Intensity-modulated Radiotherapy.
AB - AIMS: To quantify and qualify late genitourinary toxicity in a cohort of patients
with localised prostate cancer treated with image-guided intensity-modulated
radiotherapy (IMRT) to doses >=78 Gy. MATERIALS AND METHODS: The cohort consisted
of 300 patients treated with definitive dose-escalated IMRT between 2007 and
2013. Ninety-seven patients received 78-80 Gy in 38 fractions, and 203 received
82-84 Gy in 40 fractions. International Prostate Symptoms Score (IPSS) and
supplemental quality of life data were recorded at baseline, weekly during
treatment and at follow-up. Genitourinary toxicities were recorded using modified
Radiation Therapy Oncology Group criteria during weekly treatment review and at
each follow-up. Kaplan-Meier curves were used to assess the cumulative incidence
of grade >= 2 genitourinary toxicity at 3 years. Baseline patient characteristics
and symptoms were then used in univariate and multivariate analyses to identify
predictors of late urinary toxicity. RESULTS: The median follow-up was 58 months
(range 9-109 months). The actuarial cumulative 3 year rates of grade >= 2 and
grade 3 genitourinary toxicity were 14.9% and 2.8%, respectively. There was no
grade 4 toxicity. History of transurethral resection of the prostate (TURP),
alpha blocker use before radiation, any hormone use, baseline IPSS >= 14 and pre
existing incontinence or nocturia were significantly associated with late >= 2
genitourinary toxicity on univariate analysis. On multivariate analysis, only
previous TURP retained significance, with a hazard ratio of 2.54 (P=0.002).
CONCLUSION: Our study showed acceptable levels of late grade 2 genitourinary
toxicity and low rates of late grade 3 genitourinary toxicity in a cohort of
patients with prostate cancer treated with image-guided IMRT to doses between 78
and 84 Gy. Variables associated with increased late >= 2 genitourinary toxicity
include previous TURP, alpha blocker use, hormone use and pre-existing urinary
dysfunction.
PMID- 28416262
TI - Use of dilute ammonia gas for treatment of 1,2,3-trichloropropane and explosives
contaminated soils.
AB - Laboratory studies were performed to test a novel reactive gas process for in
situ treatment of soils containing halogenated propanes or explosives. A soil
column study, using a 5% ammonia-in-air mixture, established that the treatment
process can increase soil pH from 7.5 to 10.2. Batch reactor experiments were
performed to demonstrate contaminant destruction in sealed jars exposed to
ammonia. Comparison of results from batch reactors that were, and were not,
exposed to ammonia demonstrated reductions in concentrations of 1,2,3
trichloropropane (TCP), 1,3-dichloropropane (1,3-DCP), 1,2-dicholoropropane (1,2
DCP) and dibromochloropropane (DBCP) that ranged from 34 to 94%. Decreases in TCP
concentrations at 23 degrees C ranged from 37 to 65%, versus 89-94% at 62
degrees C. A spiked soil column study was also performed using the same set of
contaminants. The study showed a pH penetration distance of 30 cm in a 2.5 cm
diameter soil column (with a pH increase from 8 to > 10), due to treatment via 5%
ammonia gas at 1 standard cubic centimeter per minute (sccm) for 7 days. Batch
reactor tests using explosives contaminated soils exhibited a 97% decrease in
2,4,6-trinitrotoluene (TNT), an 83% decrease in nitrobenzene, and a 6% decrease
in hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). A biotransformation study was
also performed to investigate whether growth of ammonia-oxidizing microorganisms
could be stimulated via prolonged exposure of soil to ammonia. Over the course of
the 283 day study, only a very small amount of nitrite generation was observed;
indicating very limited ammonia monooxygenase activity. Overall, the data
indicate that ammonia gas addition can be a viable approach for treating
halogenated propanes and some types of explosives in soils.
PMID- 28416263
TI - The keys to conservative treatment of early-stage squamous cell carcinoma of the
tonsillar region.
AB - To analyze the medical literature devoted to work-up, epidemiology, local
control, survival, complications and sequelae after conservative treatment for
early-stage squamous cell carcinoma of the tonsillar region. An analysis of the
PubMed (1975-2016) database was performed using the following keywords and
associations: "tonsil/tonsillar region/oropharynx" AND "squamous cell carcinoma"
AND "early-stage (I-II; T1-2N0M0)" AND "radiation therapy/radiotherapy" OR
"conservative surgery/oropharyngectomy/transoral surgery/radical tonsillectomy".
The search retrieved 10 retrospective series documenting local control and/or
survival in series with more than 50 cases and a minimum 2 years' follow-up after
conservative treatment; no prospective studies, meta-analyses and/or Cochrane
analyses were found. Magnetic resonance imaging is the key radiological exam for
local extension assessment. Human papilloma virus infection (HPV) is a risk
factor that must be screened for systematically, since it induces tumoral radio
sensitivity and increases the risk of specific synchronous and metachronous
second primaries. Whatever conservative treatment used, local control and
survival rates higher than 85% were achieved. Implementing intensity-modulated
radiation therapy reduced the incidence and severity of radiation-related
complications and sequelae. Transoral surgery yielded very low
morbidity/mortality rates, enabled association to ipsilateral neck dissection,
and allowed radiation therapy to be reserved for the management of metachronous
second primaries. Transoral surgery appeared to be the first-line option in the
majority of cases. Lifetime follow-up adapted to HPV status is mandatory. The
development of HPV vaccination does not mean that campaigns against smoking and
alcohol abuse are of diminished importance.
PMID- 28416261
TI - Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell
Lung Cancer.
AB - INTRODUCTION: The prognosis of patients with small cell lung cancer (SCLC)
remains very poor. Therefore, the development of new therapeutic approaches,
including immunotherapies, is desirable. PATIENTS AND METHODS: We conducted a
phase II study of personalized peptide vaccination (PPV), in which a maximum of 4
human leukocyte antigen-matched peptides were selected from 31 pooled peptides
according to the pre-existing peptide-specific IgG responses before vaccination.
The PPV was subcutaneously administered. RESULTS: Forty-six patients were
enrolled (median age, 63 years; 40 patients were men). Grade 1 (n = 13), 2 (n =
10), or 3 (n = 1) skin reactions at the injection sites were observed; however,
no other severe adverse events related to the PPV were observed. The median
survival time was 466, 397, 401, and 107 days in the subgroups with 0 (n = 5), 1
(n = 15), 2 (n = 12), and >= 3 (n = 14) previous chemotherapy regimens,
respectively. Peptide-specific IgG responses to the vaccinated peptides were
augmented in 70% and 95% of patients after 1 and 2 vaccination cycles,
respectively. The overall survival (OS) of patients with augmented IgG responses
to a greater number of nonvaccinated peptides after the second cycle of
vaccination was significantly longer (median survival time, 1237 days vs. 382
days; P = .010). In addition, augmentation of IgG responses specific to 6
peptides, including Lck-derived peptides, was significantly related to better OS
(P < .05, in each peptide). CONCLUSION: These results suggest the feasibility of
PPV for SCLC patients from the viewpoints of safety, immune boosting, and
possible prolongation of OS. Therefore, further evaluation of PPV for advanced
SCLC in prospective randomized trials is warranted.
PMID- 28416264
TI - Editor's Choice - Inequalities in Abdominal Aortic Aneurysm Screening in England:
Effects of Social Deprivation and Ethnicity.
AB - OBJECTIVE: Population screening for abdominal aortic aneurysm (AAA) in men is
currently ongoing in several countries. The aim was to examine the effects of
deprivation and ethnicity on uptake of screening for abdominal aortic aneurysm
(AAA) and prevalence of AAA. METHODS: This was a review of outcomes from a
population screening programme using data collected contemporaneously on a
bespoke national database. Men aged 65 in two annual cohorts (2013/14 and
2014/15) were invited for AAA screening. Attendance and prevalence of AAA (aortic
diameter >2.9 cm) were recorded. Results were compared according to measures of
social deprivation and recorded ethnicity. RESULTS: Some 593,032 men were invited
and 461,898 attended for ultrasound screening; uptake 77.9%. Uptake was related
to social deprivation: 65.1% in the most deprived decile, 84.1% in the least
deprived: OR for least deprived 2.84, 95% CI 2.76-2.92, p<.0001. Men in deprived
areas were more likely to actively decline screening: 6% versus 3.8% in the least
deprived decile. AAA were twice as common in the most deprived compared with the
least deprived decile: OR 2.1, 95% CI 1.77-2.27, p<.0001. AAA were more common in
white British men than in black (OR 0.46, 95% CI 0.31-0.71) or Asian (OR 0.18,
95% CI 0.13-0.26) men. There was considerable local variation in all findings.
CONCLUSIONS: Social deprivation affects uptake of AAA screening in 65 year old
men. Local factors are the most important determinants of uptake, so solutions to
improve uptake must be designed at local, not national level.
PMID- 28416265
TI - Comparison of outcomes for pediatric paraphimosis reduction using topical
anesthetic versus intravenous procedural sedation.
AB - BACKGROUND: Paraphimosis is an acute urologic emergency requiring urgent manual
reduction, frequently necessitating procedural sedation (PS) in the pediatric
population. The present study sought to compare outcomes among pediatric patients
undergoing paraphimosis reduction using a novel topical anesthetic (TA) technique
versus PS. METHODS: We performed a retrospective analysis of all patients
<18years old, presenting to a tertiary pediatric ED requiring analgesia for
paraphimosis reduction between October 2013 and September 2016. The primary
outcome was reduction first attempt success; secondary outcomes included
Emergency Department length of stay (ED LOS), adverse events and return visits.
Dichotomous outcomes were analyzed by Chi-square testing and multivariate linear
regression was used to compare continuous variables. RESULTS: Forty-six patients
were included; 35 underwent reduction using TA, 11 by PS. Patient age and
duration of paraphimosis at ED presentation did not differ between groups. There
was no difference in first attempt success between TA (32/35, 91.4%) and PS
groups (9/11, 81.8%; p=0.37). Mean ED LOS was 209min shorter for TA patients
(148min vs. 357min, p=0.001) and remained significantly shorter after controlling
for age and duration of paraphimosis (adjusted mean difference -198min, p=0.003).
There were no return visits or major adverse events in either group, however,
among successful reduction attempts, PS patients more frequently experienced
minor adverse events (7/9 vs. 0/32, p<0.001). CONCLUSIONS: Paraphimosis reduction
using TA was safe and effective. Compared to PS, TA was associated with a reduced
ED LOS and fewer adverse events. TA could potentially allow more timely reduction
with improved patient experience and resource utilization.
PMID- 28416266
TI - Removing default dispense quantity from opioid prescriptions in the electronic
medical record.
PMID- 28416267
TI - Molecular Mechanisms and Targets of Therapy for Hepatocellular Carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC
develops through a multistep process that involves the local tumor
microenvironment, intracellular signaling pathways, and altered metabolic system
that allows the cancer proliferation. Understanding the mechanisms of tumor
development and progression is critical to developing improved therapies aimed at
better survival. This article reviews the molecular mechanisms of HCC development
and highlights the potential therapeutic targets for treatments.
PMID- 28416268
TI - Post-traumatic Stress Disorder and Risk of Parkinson Disease: A Nationwide
Longitudinal Study.
AB - OBJECTIVE: Increasing evidence has suggested a relationship between post
traumatic stress disorder (PTSD) and neurodegenerative disorder, such as
Alzheimer disease. The association between PTSD and Parkinson disease (PD),
however, remains unclear. METHOD: Using the Taiwan National Health Insurance
Research Database, 7,280 subjects (1,456 patients aged >=45 years with PTSD and
5,824 age-/sex-matched individuals without PTSD) were enrolled between 2002 and
2009 and followed to the end of 2011. Subjects who developed PD during the follow
up period were identified. RESULTS: An increased risk of developing PD was found
in patients with PTSD (Wald chi2 = 12.061, hazard ratio [HR]: 3.46, 95%
confidence interval [CI]: 1.72-6.96) compared with individuals without PTSD,
after adjusting for demographic data and medical and psychiatric comorbidities.
The sensitivity tests after excluding the first year observation (Wald chi2 =
7.948, HR: 3.01, 95% CI: 1.40-6.46) and the first 3-year observation (Wald chi2 =
5.099, HR: 3.07, 95% CI: 1.16-8.15) were consistent. CONCLUSIONS: Patients with
PTSD had an elevated risk of developing PD in later life. Further studies would
be required to clarify the exact pathophysiology between PTSD and PD and to
investigate whether the prompt intervention for PTSD may reduce this risk.
PMID- 28416269
TI - DNA-Protein Crosslink Proteolysis Repair.
AB - Proteins that are covalently bound to DNA constitute a specific type of DNA
lesion known as DNA-protein crosslinks (DPCs). DPCs represent physical obstacles
to the progression of DNA replication. If not repaired, DPCs cause stalling of
DNA replication forks that consequently leads to DNA double-strand breaks, the
most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of
DPC repair was unclear until now. Recent work unveiled that DPC repair is
orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN
in metazoans and Wss1 in yeast. This review summarizes recent discoveries on two
proteases in DNA replication-coupled DPC repair and establishes DPC proteolysis
repair as a separate DNA repair pathway for genome stability and protection from
accelerated aging and cancer.
PMID- 28416270
TI - Plasma levels and leucocyte RNA expression of adipokines in young patients with
coronary artery disease, in metabolic syndrome and healthy controls.
AB - OBJECTIVES: Little is known about the role of adipokines in the pathogenesis of
coronary artery disease in young patients. The aims of this study were to compare
serum levels of adipokines and expression of adipokines in peripheral blood
leukocytes in patients with premature coronary artery disease (CAD), metabolic
syndrome and healthy individuals. DESIGN AND METHODS: Sixty-five patients with
premature CAD (men 18-45years old and women 18-55years old) formed the study
group. The control groups were 75 patients with metabolic syndrome and 50 healthy
individuals. For each group, RNA expression in peripheral blood leukocytes was
determined for 24 different adipokines and 11 adipokines were examined in serum.
RESULTS: In individuals with CAD, serum visfatin levels were significantly higher
than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7ug/L,
P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3ug/L, P<0.001) and ZAG2
(45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating
curve (ROC) analysis for testing the validity of these adipokines in the
diagnosis of CAD compared to control groups provided the following areas under
the curve (AUC): omentin-1 AUC 0.97 (cut-off <=222ug/L), ZAG2 AUC 0.89 (cut-off
<=51.7mg/L) and visfatin AUC 0.74 (cut-off >=1.0ug/L) (P<0.001 in all cases).
Visfatin and omentin-1 serum levels did not differ between the acute phase of
myocardial infarction and the chronic phase of CAD. In patients with CAD, we
found no significant relation between mRNA expression and adipokine
concentration. CONCLUSION: Serum omentin-1, visfatin and ZAG2 could serve as
biomarkers of premature CAD in young apparently healthy people.
PMID- 28416271
TI - The challenge of criteria for interstitial pneumonia with autoimmune features.
PMID- 28416272
TI - Biocidal effects of Piper hispidinervum (Piperaceae) essential oil and synergism
among its main components.
AB - In this study we evaluated the effect of a pressure gradient (1-2 atm) in the
extraction and composition of the essential oil (EO) of Piper hispidinervum by
steam distillation. We also evaluated the insect antifeedant effects (Spodoptera
littoralis, Leptinotarsa decemlineata, Myzus persicae and Rhopalosiphum padi) and
nematicidal activity (Meloidogyne javanica) of the oils, their major components
and their synergistic interactions. Safrole was the major component (78-81%)
followed by terpinolene (5-9%). The EOs tested were effective insect
antifeedants. Safrole, explained most of the insect antifeedant action of P.
hispidinervum EOs. When safrole and terpinolene were tested in binary
combinations, low ratios of safrole improved the antifeedant effects of
terpinolene. P. hispidinervum EOs caused higher mortality of M. javanica
juveniles than their major components. In binary combinations, low ratios of
terpinolene increased the nematicidal effects of safrole. The EO treatment
strongly suppressed nematode egg hatching and juvenile infectivity. P.
hispidinervum EOs affected the germination of S. lycopersicum and L. sativa
mostly at 24 h of treatment, being L. sativa the most sensitive. Safrole
moderately affected germination and root growth of L. sativa, S. lycopersicum and
L. perenne. Terpinolene only affected S. lycopersicum root growth.
PMID- 28416273
TI - Attention allocation and social worries predict interpretations of peer-related
social cues in adolescents.
AB - Adolescence is a sensitive period for increases in normative but also
debilitating social fears and worries. As the interpretation of interpersonal
cues is pertinent to social anxiety, investigating mechanisms that may underlie
biases in social cue appraisal is important. Fifty-one adolescents from the
community aged 14-19 were presented with self- and other-relevant naturalistic
social scenes for 5s and then required to rate either a negative or a positive
interpretation of the scene. Eye-tracking data were collected during the free
viewing period to index attentional deployment. Individual differences in social
worries were measured via self-report. Social anxiety levels significantly
predicted biases in interpretation ratings across scenes. Additionally,
cumulative attentional deployment to peer cues also predicted these
interpretation biases: participants who spent more time on facial displays
perceived more threat, i.e. endorsed more negative and less positive
interpretations. Self-relevant scenes yielded greater tendencies to draw negative
interpretations. Finally, older adolescents also selected more benign
interpretations. Social anxiety is associated with a bias in interpreting social
cues; a cognitive bias that is also influenced by attentional deployment. This
study contributes to our understanding of the possible attention mechanisms that
shape cognitions relevant to social anxiety in this at-risk age group.
PMID- 28416274
TI - Fatigue in multiple sclerosis - Insights into evaluation and management.
AB - Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease
of the central nervous system, characterized by the accumulation of numerous
neurological symptoms and signs throughout its course. Fatigue is one of the most
distressing complaints that MS patients may experience over their lifetime. In
spite of its high prevalence, the pathophysiology of MS fatigue is far from being
fully elucidated and a constellation of mechanisms seems implicated in this
setting. Several factors could contribute to its development and/or exacerbation,
and this requires a careful workup in order to search for all possible underlying
causes, such as sleep disturbances, endocrine dysfunction and mood disorders, to
cite a few. The aim of this review is to revisit the definition of MS fatigue,
provide an overview of its pathophysiology, and reappraise its clinical,
structural and functional correlates. Additionally, we discuss the available
assessment tools, as well as the various management strategies including
pharmacological and non-pharmacological interventions. Special emphasis will be
placed on the role of noninvasive brain stimulation techniques in this field.
Finally, we propose a "road map" to facilitate the diagnosis and guide the
therapeutic regimens of this multifactorial and multidimensional construct.
PMID- 28416275
TI - Cisplatin Analogs Confer Protection against Cyanide Poisoning.
AB - Cisplatin holds an illustrious position in the history of chemistry most notably
for its role in the virtual cure of testicular cancer. Here we describe a role
for this small molecule in cyanide detoxification in vivo. Cyanide kills
organisms as diverse as insects, fish, and humans within seconds to hours.
Current antidotes exhibit limited efficacy and are not amenable to mass
distribution requiring the development of new classes of antidotes. The binding
affinity of the cyanide anion for the positively charged metal platinum is known
to create an extremely stable complex in vitro. We therefore screened a panel of
diverse cisplatin analogs and identified compounds that conferred protection from
cyanide poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery
pipeline begins to establish the characteristics of platinum ligands that
influence their solubility, toxicity, and efficacy, and provides proof of concept
that platinum-based complexes are effective antidotes for cyanide poisoning.
PMID- 28416276
TI - Synthesis and Degradation of Adenosine 5'-Tetraphosphate by Nicotinamide and
Nicotinate Phosphoribosyltransferases.
AB - Adenosine 5'-tetraphosphate (Ap4) is a ubiquitous metabolite involved in cell
signaling in mammals. Its full physiological significance remains unknown. Here
we show that two enzymes committed to NAD biosynthesis, nicotinamide
phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase
(NAPT), can both catalyze the synthesis and degradation of Ap4 through their
facultative ATPase activity. We propose a mechanism for this unforeseen
additional reaction, and demonstrate its evolutionary conservation in bacterial
orthologs of mammalian NAMPT and NAPT. Furthermore, evolutionary distant forms of
NAMPT were inhibited in vitro by the FK866 drug but, remarkably, it does not
block synthesis of Ap4. In fact, FK866-treated murine cells showed decreased NAD
but increased Ap4 levels. Finally, murine cells and plasma with engineered or
naturally fluctuating NAMPT levels showed matching Ap4 fluctuations. These
results suggest a role of Ap4 in the actions of NAMPT, and prompt to evaluate the
role of Ap4 production in the actions of NAMPT inhibitors.
PMID- 28416277
TI - Radiology Education: It Takes a Village!
PMID- 28416278
TI - AI-2 quorum sensing negatively regulates rbf expression and biofilm formation in
Staphylococcus aureus.
AB - Staphylococcus aureus is an important pathogen that is capable of forming
biofilms on biomaterial surfaces to cause biofilm-associated infections.
Autoinducer 2 (AI-2), a universal language for interspecies communication, is
involved in a variety of physiological activities, although its exact role in
Gram-positive bacteria, especially in S. aureus, is not yet thoroughly
characterized. Herein we demonstrate that inactivation of luxS, which encodes AI
2 synthase, resulted in increased biofilm formation and higher polysaccharide
intercellular adhesion (PIA) production compared with the wild-type strain in S.
aureus NCTC8325. The transcript level of rbf, a positive regulator of biofilm
formation, was significantly increased in the luxS mutant. All of the parental
phenotypes could be restored by genetic complementation and chemically
synthesized 4,5-dihydroxy-2,3-pentanedione, the AI-2 precursor molecule,
suggesting that AI-2 has a signaling function to regulate rbf transcription and
biofilm formation in S. aureus. Phenotypic analysis revealed that the luxS rbf
double mutant produced approximately the same amount of biofilms and PIA as the
rbf mutant. In addition, real-time quantitative reverse transcription-PCR
analysis showed that the icaA transcript level of the rbf mutant was similar to
that of the luxS rbf double mutant. These findings demonstrate that the LuxS/AI-2
system regulates PIA-dependent biofilm formation via repression of rbf expression
in S. aureus. Furthermore, we demonstrated that Rbf could bind to the sarX and
rbf promoters to upregulate their expression.
PMID- 28416279
TI - The impact of work-life balance on intention to stay in academia: Results from a
national survey of pharmacy faculty.
AB - PURPOSE: Border-Crossing theory suggests work-life balance and career
satisfaction are inter-related and disappointment in work-life balance may
predict changes in one's career path. Application of this theory to health
profession faculty is plausible but has not been fully explored. The purpose of
this study is to examine factors related to reported career change intention
among United States pharmacy school faculty and to determine if Border-Crossing
theory fits these observations. METHODS: Results from a national web-based survey
administered via Qualtrics(r) to American Association of Colleges of Pharmacy
(AACP) members were utilized. Bivariate analyses were conducted to compare
differences among faculty stating an intention to stay or leave academia. A
logistic multivariate model was used to determine if work-life balance remains
significant when controlling for other variables and if survey results support
the Border-Crossing theory. RESULTS: Nearly all (seven hundred of 811 responders,
or 86.3%) stated a desire to stay in academia. Faculty with higher work-life
balance were more likely to report an intent to remain in academia. Male, older,
full-professor and non-pharmacy practice faculty (social or administrative
science, pharmacology, medicinal chemistry and others) were more likely to state
an intention to remain in academia relative to their counterparts. Lower stress,
as measured by the validated Perceived Stress Scale (PSS) scores, was seen among
faculty stating a desire to remain in academia. Work-life balance remained
significantly inversely related to career change intention after controlling for
all other factors. CONCLUSION: A significant factor related to pharmacy faculty's
stated intention to remain in academia was work-life balance. Other factors such
as gender, age, rank, stress level and department may also play a role. These
results support the application of the Border-Crossing theory in health
profession faculty and may provide pharmacy school administrators and
stakeholders with insight to foster faculty retention and decrease faculty
turnover.
PMID- 28416280
TI - Progress toward Gene Therapy for Duchenne Muscular Dystrophy.
AB - Duchenne muscular dystrophy (DMD) has been a major target for gene therapy
development for nearly 30 years. DMD is among the most common genetic diseases,
and isolation of the defective gene (DMD, or dystrophin) was a landmark
discovery, as it was the first time a human disease gene had been cloned without
knowledge of the protein product. Despite tremendous obstacles, including the
enormous size of the gene and the large volume of muscle tissue in the human
body, efforts to devise a treatment based on gene replacement have advanced
steadily through the combined efforts of dozens of labs and patient advocacy
groups. Progress in the development of DMD gene therapy has been well documented
in Molecular Therapy over the past 20 years and will be reviewed here to
highlight prospects for success in the imminent human clinical trials planned by
several groups.
PMID- 28416281
TI - Population structure of Han nationality in Central-Southern China.
AB - Knowledge of population structure is very important for forensic genetics.
However, the population substructure in Central-Southern China Han nationality
has still not been fully described. In this study, we investigated the genetic
diversity of 15 forensic autosomal STR loci from 6879 individuals in 12 Han
populations subdivided by administrative provinces in Central-Southern China. The
statistical analysis of genetic variation showed that genetic differentiation
among these populations was very small with a Fst value of 0.0009. The
Discriminant Analysis of Principal Components (DAPC) showed that there were no
obvious population clusters in Central-Southern China Han population. In
practice, the population structure effect in Central-Southern China Han
population can be negligible in forensic identification and paternity testing.
PMID- 28416282
TI - Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells.
AB - Research on human brain development and neurological diseases is limited by the
lack of advanced experimental in vitro models that truly recapitulate the
complexity of the human brain. Here, we describe a robust human brain organoid
system that is highly specific to the midbrain derived from regionally patterned
neuroepithelial stem cells. These human midbrain organoids contain spatially
organized groups of dopaminergic neurons, which make them an attractive model for
the study of Parkinson's disease. Midbrain organoids are characterized in detail
for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we
show the presence of synaptic connections and electrophysiological activity. The
complexity of this model is further highlighted by the myelination of neurites.
The present midbrain organoid system has the potential to be used for advanced in
vitro disease modeling and therapy development.
PMID- 28416283
TI - Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with
Metabolic Disease.
AB - The striking rise of obesity-related metabolic disorders has focused attention on
adipocytes as critical mediators of disease phenotypes. To better understand the
role played by excess adipose in metabolic dysfunction it is crucial to decipher
the transcriptional underpinnings of the low-grade adipose inflammation
characteristic of diseases such as type 2 diabetes. Through employing a
comparative transcriptomics approach, we identified IRF1 as differentially
regulated between primary and in vitro-derived genetically matched adipocytes.
This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar
to its function in other tissues. Utilizing adipose-derived mesenchymal
progenitors we subsequently demonstrated that expression of IRF1 in adipocytes
indeed contributes to upregulation of inflammatory processes, both in vitro and
in vivo. This highlights IRF1's relevance to obesity-related inflammation and the
resultant metabolic dysregulation.
PMID- 28416284
TI - Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic
Stem Cell Emergence, Migration, and Niche Colonization.
AB - Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from
hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically,
the cellular mechanism(s) allowing HSPC egress and migration to secondary niches
are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation
responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular
interactions, and signaling. Here, inhibition of vascular-associated Mmp2
function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb+
HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization;
these defects were absent in fibronectin mutants, indicating that Mmp2
facilitates endothelial-to-hematopoietic transition via ECM remodeling. In
contrast, Mmp9 was dispensable for HSPC budding, being instead required for
proper colonization of secondary niches. Significantly, these migration defects
were mimicked by overexpression and blocked by knockdown of C-X-C motif chemokine
12 (cxcl12), suggesting that Mmp9 controls CHT homeostasis through chemokine
regulation. Our findings indicate Mmp2 and Mmp9 play distinct but complementary
roles in developmental HSPC production and migration.
PMID- 28416285
TI - Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron
Subclass Fate from Embryonic Stem Cells.
AB - Recent studies indicate that the location of neurogenesis within the medial
ganglionic eminence (MGE) critically influences the fate determination of
cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating
from subventricular zone divisions and somatostatin (Sst) interneurons primarily
arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate
the transition from apical to basal progenitor and their differentiation into
post-mitotic neurons. We find that aPKC inhibition enhances intermediate
neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly
increased ratio of Pv- to Sst-expressing interneurons. Conversely, inhibition of
Notch signaling enriches for Sst subtypes at the expense of Pv fates. These
findings confirm that the mode of neurogenesis influences the fate of MGE-derived
interneurons and provide a means of further enrichment for the generation of
specific interneuron subgroups from pluripotent stem cells.
PMID- 28416286
TI - In Vivo RNAi Screen Unveils PPARgamma as a Regulator of Hematopoietic Stem Cell
Homeostasis.
AB - Hematopoietic stem cell (HSC) defects can cause repopulating impairment leading
to hematologic diseases. To target HSC deficiency in a disease setting, we
exploited the repopulating defect of Fanconi anemia (FA) HSCs to conduct an in
vivo short hairpin RNA (shRNA) screen. We exposed Fancd2-/- HSCs to a lentiviral
shRNA library targeting 947 genes. We found enrichment of shRNAs targeting genes
involved in the PPARgamma pathway that has not been linked to HSC homeostasis.
PPARgamma inhibition by shRNA or chemical compounds significantly improves the
repopulating ability of Fancd2-/- HSCs. Conversely, activation of PPARgamma in
wild-type HSCs impaired hematopoietic repopulation. In mouse HSCs and patient
derived lymphoblasts, PPARgamma activation is manifested in upregulating the p53
target p21. PPARgamma and co-activators are upregulated in total bone marrow and
stem/progenitor cells from FA patients. Collectively, this work illustrates the
utility of RNAi technology coupled with HSC transplantation for the discovery of
novel genes and pathways involved in stress hematopoiesis.
PMID- 28416287
TI - Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial
Registration and Publications.
AB - We assessed the extent to which the publication of clinical trial results of
innovative cell-based interventions reflects International Society for Stem Cell
Research best practice guidelines. We assessed: (1) characteristics and time to
publication of completed trials; (2) quality of reported trials; and (3) results
of published trials. We identified and analyzed publications from 1,052 novel
stem cell clinical trials: 179 (45.4%) of 393 completed trials had published
results; 48 trials were registered by known stem cell tourism clinics, none of
which reported results. Completed non-industry-sponsored trials initially
published more rapidly, but differences with industry-sponsored trials decreased
over time. Most publications reported safety, and 67.3% (mainly early-stage
trials) reported positive outcomes. A higher proportion of industry trials
reported positive efficacy. Heightened patient expectations for stem cell
therapies give rise to ethical obligations for the transparent conduct of
clinical trials. Reporting guidelines need to be developed that are specific to
early-phase clinical trials.
PMID- 28416288
TI - Repeat Fibrinolysis to Treat Thrombotic Dysfunction of a Mitral Valve-in-valve
Prosthesis.
PMID- 28416289
TI - Impact of Autoimmune Disease on the Management and Prognosis of Acute Coronary
Syndrome.
PMID- 28416290
TI - Diagnostic and Prognostic Findings in Patients With Positive Clinical or ECG
Exercise Tests in the Absence of Echocardiographic Abnormalities.
PMID- 28416291
TI - Cumulative live birth rate after GnRH agonist trigger and elective
cryopreservation of all embryos in high responders.
AB - Elective embryo cryopreservation after using gonadotrophin-releasing hormone
(GnRH) antagonist protocols and GnRH agonist triggering is becoming an
increasingly important part of medically assisted reproduction. We designed a
single-centre retrospective study to assess the cumulative probability of
achieving a live birth through consecutive transfers of vitrified-warmed
blastocysts after elective embryo cryopreservation in high-responding patients.
Hence, 123 women identified to be at high risk for developing ovarian
hyperstimulation syndrome were included. They were stimulated using GnRH
antagonist protocol, and GnRH agonist was used to trigger final oocyte
maturation. All embryos were vitrified at the blastocyst stage and transferred in
the subsequent menstrual cycles. Using the Kaplan-Meier survival analysis, a
total of 65.9% (95% CI 57.5 to 74.3) women achieved a live birth after a maximum
of six embryo transfer cycles using the 'conservative' approach. Applying the
'optimistic' approach, presuming that women who still had cryopreserved embryos
and did not return for embryo transfer had the same chance of achieving a live
birth as those returning for transfer, the cumulative live birth rate estimated
in six embryo transfer cycles was 76.6% (95% CI 69.1 to 84.1). No cases of severe
ovarian hyperstimulation syndrome were recorded.
PMID- 28416292
TI - Participation of Emergency Radiologists in Tort Reform.
PMID- 28416293
TI - Sustaining Change in Radiology Education: The Need for Universal Curricula.
PMID- 28416294
TI - Radiologists May Now Be Accountable for Containing Medicare Costs and Spending
Under MACRA.
PMID- 28416295
TI - Depressive symptoms in schizophrenia and dopamine and serotonin gene
polymorphisms.
AB - Although depressive symptoms seem to be frequent in schizophrenia they have
received significantly less attention than other symptom domains. As impaired
serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis
of depression and schizophrenia this study sought to investigate the putative
association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A
VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this
study were to closely examine schizophrenia symptom domains by performing factor
analysis of the two most used instruments in this setting (Positive and negative
syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine
the influence of investigated gene polymorphisms on the schizophrenia symptom
domains, focusing on depressive scores. A total of 591 participants were included
in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%)
of schizophrenic patients had significant depressive symptoms. Genotype
distribution revealed no significant differences regarding all investigated
polymorphisms except the separate gender analysis for MAO-A gene polymorphism
which revealed significantly more allele 3 carriers in schizophrenic males.
Factor analysis of the PANSS scale revealed the existence of five separate
factors (symptom domains), while the CDSS scale revealed two distinct factors.
Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT)
significantly influenced two factors from the PANSS (aggressive/impulsive and
negative symptoms) and one from the CDSS scale (suicidality), respectively.
Depressive symptoms in schizophrenic patients may be influenced by functional
gene polymorphisms, especially those implicated in serotonergic
neurotransmission.
PMID- 28416296
TI - HIV infection and aortic stiffness.
AB - People living with human immunodeficiency virus (HIV) infection and receiving
antiretroviral therapy now have the same life expectancy as the general
population. However, they have a higher risk of atherosclerotic cardiovascular
events because of a complex and polyfactorial vasculopathy, combining the effects
of antiretroviral therapy, the HIV virus itself, immune activation, chronic
inflammation and metabolic disturbances. Whether people living with HIV infection
experience increased vascular aging compared with the general population remains
controversial. To summarize current knowledge of the association between HIV
infection and aortic stiffness as a marker of vascular aging. This review
included 18 clinical studies in adult populations, published between 2009 and
2016, and identified on PubMed/MEDLINE or other databases. Search terms were
aortic stiffness, arterial stiffness, vascular aging, pulse wave velocity and
HIV. All 18 studies were observational, and compared groups infected (HIV+) and
not infected (HIV-) with HIV. Ten studies (55%) reported no significant
differences in aortic stiffness between HIV+ groups and age-matched HIV- control
groups. The main reported determinants of aortic stiffness were age, blood
pressure, smoking, metabolic syndrome and HIV-related variables, including
CD4/CD8 ratio, current T-CD4 count < 200/mm3 and nadir T-CD4+ count < 200/mm3. We
found discordant results regarding whether HIV+ patients had increased aortic
stiffness compared with HIV- controls. However, HIV-related conditions were
associated with vascular health. This association has been confirmed in recent
prospective studies. There is emerging evidence that HIV itself and immune
activity affect vascular health and the large arteries.
PMID- 28416297
TI - Cry toxin specificities of insect ABCC transporters closely related to
lepidopteran ABCC2 transporters.
AB - In this study, we examined insect and human ABCC transporters closely related to
the lepidopteran ABC transporter C2 (ABCC2), a powerful receptor for the Bacillus
thuringiensis Cry toxin, for their responses to various Cry toxins. ABCC2 and the
lepidopteran ABC transporter C3 (ABCC3) conferred cultured cells with
susceptibility to a lepidopteran-specific Cry1Aa toxin but not to lepidopteran
specific Cry1Ca and Cry1Da. One coleopteran ABCC transporter specifically
responded to a coleopteran-specific Cry8Ca toxin. ABCC transporters from a
dipteran insect and humans did not respond to any of the tested Cry toxins that
are active to lepidopteran and coleopteran insects. These results yield important
information for our understanding of insect specificity of Cry toxins and provide
the first demonstration of a coleopteran ABCC transporter that serves as a Cry
toxin receptor.
PMID- 28416298
TI - [Epicutaneous patch testing in delayed drug hypersensitivity reactions induced by
antiepileptic drugs].
AB - INTRODUCTION: Antiepileptic drugs are widely used and are associated with
numerous side effects including skin eruptions. Epicutaneous tests have been used
with variable success in skin drug reactions. The purpose of this study was to
evaluate the profitability of epicutaneous tests in delayed hypersensitivity
reactions induced by antiepileptic drugs. METHODS: We analyzed all cases of
allergic skin reactions to antiepileptic drugs notified in regional
pharmacovigilance center of Sfax (Tunisia) between June 1, 2014 and April 30,
2016. The imputation score, determined using the French imputation method, should
be at least doubtful. Patch-tests were performed in accordance with the general
Europen network on Drug Allergy/European Academy of Allergy and Clinical
Immunology (ENDA/EAACI) guidelines. Patch-tests were read according to the
generally accepted criteria of the International contact dermatitis research
group (ICDRG). RESULTS: In our study, 20 patients were included, among which 23
events were observed. The drug involved in delayed hypersensitivity reactions was
carbamazepine in 11 cases, phenobarbital in 10 cases and valproic acid in 4
cases. The clinical reactions caused by the drug were classified as maculopapular
exanthema (11 cases), DRESS syndrome (6 cases), Stevens-Johnson syndrome (2
cases), fixed drug eruption (2 cases) and erythroderma (2 cases). Patch-tests
were positive in 19 patients (95 %). Cross-reactivity between antiepileptic drugs
was observed in 4 cases: between valproic acid and carbamazepine in 2 cases
between valproic acid and phenobarbital in 1 case and between phenobarbital and
carbamazepine in 1 case. CONCLUSION: In this study, patch testing was a safe and
useful method in confirming the culprit drug in delayed hypersensitivity
reactions induced by antiepileptic drugs.
PMID- 28416299
TI - Malignant Mesothelioma of the Tunica Vaginalis Testis: Outcomes Following
Surgical Management Beyond Radical Orchiectomy.
AB - OBJECTIVE: To describe clinical management and outcomes of a cohort of patients
with malignant mesothelioma of the tunica vaginalis testis (MMTVT) who received
treatments beyond radical orchiectomy. METHODS: Patients with confirmed MMTVT at
a single tertiary care institution were identified. Treatments, pathologic
outcomes, and survival were recorded. Prognostic variables associated with
survival were analyzed with a Cox proportional hazards model and Kaplan-Meier
curves. RESULTS: Overall, 15 patients were included. Initial presentation was a
scrotal mass in 7 of 15 (47%) and hydrocele in 5 of 15 (33%) patients. Clinical
staging revealed enlarged nodes in 5 of 15 (33%) patients. Radical orchiectomy
was the initial treatment in 5 of 15 (33%) patients. Positive surgical margins
were found in 6 of 14 (43%) radical orchiectomies and were associated with worse
survival (P = .007). The most frequent histologic subtype was epithelioid,
associated with better survival (P = .048). Additional surgeries were performed
on 12 of 15 (80%) patients. Pathologic examination revealed MMTVT in 6 of 12
(50%) hemiscrotectomies, 7 of 8 (88%) retroperitoneal lymph node dissections, 1
of 7 (14%) pelvic lymph node dissections, and 10 of 10 (100%) groin dissections.
Five patients received adjuvant chemotherapy. Two also received adjuvant
radiation therapy. Three patients with lymph node involvement remain no evidence
of disease over 6 years after diagnosis. After a median follow-up of 3.5 years
(interquartile range: 1.2-7.2), 5 patients have died, all of MMTVT; the median
overall survival has not been reached. Common sites of relapse were lungs (5 of
7) and groin (3 of 7). CONCLUSION: The pattern of metastatic spread of MMTVT is
predominantly lymphatic. Nodes in the retroperitoneum and the groin are commonly
involved. Prognosis is poor, but there may be a role for aggressive surgical
resection including hemiscrotectomy, and inguinal and retroperitoneal lymph
nodes.
PMID- 28416301
TI - Telemedicine is the way forward for the management of cystic fibrosis - the case
in favour.
AB - Despite rapid changes in Information and Communication Technology, outpatient
chronic disease management has changed very little in decades. However, the
introduction of Telemedicine defined here as the use of remote patient-centred
clinical services including the use of video and audio connections,
telemonitoring and mobile applications provides us with an ideal opportunity to
revolutionise care. Its appeal in cystic fibrosis (CF) care is clear offering
better access to services, the opportunity of earlier intervention and improved
monitoring and self management through virtual clinics and the use of real-time
applications for adherence monitoring. It has the potential to reduce costs and
has been shown to be effective in other chronic disease conditions. There is a
lack of good quality data in CF and studies are needed to provide supportive
evidence. Nonetheless, it would seem that telemedicine is the future of CF care.
PMID- 28416300
TI - Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6
Deficient Mice.
AB - Soft tissue calcification occurs in several common acquired pathologies, such as
diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a
transmembrane transporter primarily expressed in liver and kidneys, initiates a
molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the
cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a
major calcification inhibitor. Heritable mutations in ABCC6 underlie the
incurable calcification disorder pseudoxanthoma elasticum and some cases of
generalized arterial calcification of infancy. Herein, we determined that the
administration of PPi and the bisphosphonate etidronate to Abcc6-/- mice fully
inhibited the acute dystrophic cardiac calcification phenotype, whereas
alendronate had no significant effect. We also found that daily injection of PPi
to Abcc6-/- mice over several months prevented the development of pseudoxanthoma
elasticum-like spontaneous calcification, but failed to reverse already
established lesions. Furthermore, we found that the expression of low amounts of
the human ABCC6 in liver of transgenic Abcc6-/- mice, resulting in only a 27%
increase in plasma PPi levels, led to a major reduction in acute and chronic
calcification phenotypes. This proof-of-concept study shows that the development
of both acute and chronic calcification associated with ABCC6 deficiency can be
prevented by compensating PPi deficits, even partially. Our work indicates that
PPi substitution represents a promising strategy to treat ABCC6-dependent
calcification disorders.
PMID- 28416302
TI - Effect of Bacterial Biofilm on the Osteogenic Differentiation of Stem Cells of
Apical Papilla.
AB - INTRODUCTION: Although clinical success in regenerative endodontics is
substantially high, histological success is limited to finding bone/cementum-like
tissue instead of dentin within the canal space. The aims of this study were to
investigate (1) the effect of bacterial biofilm on osteogenic gene expression in
stem cells of the apical papilla (SCAP) and (2) the effect of bacterial antigens
on the functional differentiation of SCAP into a mineralizing phenotype. METHODS:
Using an ex vivo organotypic root canal model and an American Association of
Endontists-recommended regenerative endodontic procedures, we evaluated SCAP
differentiation in the presence and absence of an Enterococcus faecalis biofilm.
Gene expression analysis for dentinogenic and osteoblastic markers was performed
with real-time polymerase chain reaction. The effect of E. faecalis antigens on
SCAP differentiation into mineralizing cells in vitro was evaluated with 2
functional assays: Alizarin Red and alkaline phosphatase activity assays.
RESULTS: After regenerative endodontic procedures, residual bacteria continued to
sustain within the root canal system. SCAP in the presence of E. faecalis biofilm
significantly downregulated dentinogenic genes such as dentin sialophosphoprotein
and upregulated osteoblastic genes such as bone sialoprotein, osteocalcin, distal
less homeobox 5, and runt-related transcription factor 2. E. faecalis antigens
significantly inhibited SCAP differentiation into a mineralizing phenotype when
alizarin red staining and alkaline phosphatase assays were used in vitro.
CONCLUSIONS: Current disinfection protocols were ineffective in eliminating
bacteria from root tips and the levels of the residual bacterial biofilm, and its
byproducts, were able to significantly alter osteogenic-differentiation of SCAP.
PMID- 28416303
TI - Effect of Instrumentation Techniques and Preparation Taper on Apical Extrusion of
Bacteria.
AB - INTRODUCTION: The aim of this in vitro study was to evaluate the effects of
different root canal instrumentation techniques and preparation tapers on the
amount of apically extruded bacteria. METHODS: The root canals of 98 extracted
human mandibular incisors were contaminated with Enterococcus faecalis
suspension. After incubation at 37 degrees C for 24 hours, the root canals were
instrumented with K3 rotary files in a crown-down (CD) or full-length linear
instrumentation technique (FL) by using 3 different root canal tapers (0.02,
0.04, and 0.06). During instrumentation, apically extruded bacteria were
collected into vials containing saline solution. The microbiological samples were
taken from the vials and incubated in brain-heart agar medium for 24 hours, and
the numbers of colony-forming units (CFUs) were determined. The obtained results
were analyzed with t test and one-way analysis of variance for the comparisons
between the instrumentation techniques (CD and FL) and the preparation tapers
(0.02, 0.04, and 0.06), respectively. Tukey honestly significant difference test
was used for pairwise comparisons. RESULTS: The preparation taper had no effect
on the number of CFUs when a FL instrumentation technique was used (P > .05).
There was a statistically significant difference in the CFUs between FL and CD
techniques when the preparation taper was 0.02 (P < .05). There was no
statistically significant difference between the 0.04 and 0.06 preparation tapers
in any of the instrumentation techniques (P > .05). CONCLUSIONS: Using a 0.02
taper in a CD manner results in the least amount of bacterial extrusion. The
instrumentation technique did not seem to affect the amount of bacterial
extrusion when 0.04 and 0.06 taper instruments were used for cleaning and shaping
the root canal space.
PMID- 28416304
TI - Micro-computed Tomographic Analysis of Apical Microcracks before and after Root
Canal Preparation by Hand, Rotary, and Reciprocating Instruments at Different
Working Lengths.
AB - INTRODUCTION: This study aimed to compare apical microcrack formation after root
canal shaping by hand, rotary, and reciprocating files at different working
lengths using micro-computed tomographic analysis. METHODS: Sixty mandibular
incisors were randomly divided into 6 experimental groups (n = 10) according to
the systems and working lengths used for the root canal preparation: ProTaper
Universal for Hand Use (Dentsply Maillefer, Ballaigues, Switzerland), HyFlex CM
(Coltene-Whaledent, Allstetten, Switzerland), and Reciproc (VDW, Munich, Germany)
files working at the apical foramen (AF) and 1 mm short of the AF (AF - 1 mm).
The teeth were imaged with micro-computed tomographic scanning at an isotropic
resolution of 14 MUm before and after root canal preparation, and the cross
sectional images generated were assessed to detect microcracks in the apical
portion of the roots. RESULTS: Overall, 17 (28.3%) specimens presented
microcracks before instrumentation. Apical microcracks were present in 1
(ProTaper Universal for Hand Use), 3 (Hyflex CM), and 2 (Reciproc) specimens when
the instrumentation terminated at the AF. When instrumentation was terminated at
AF - 1 mm, apical microcracks were detected in 3 (ProTaper Universal for Hand
Use) and 4 (Hyflex CM and Reciproc) specimens. All these microcracks detected
after root canal preparation were already present before instrumentation, and no
new apical microcrack was visualized. For all groups, the number of slices
presenting microcracks after root canal preparation was the same as before canal
preparation. CONCLUSIONS: Root canal shaping with ProTaper Universal for Hand
Use, HyFlex CM, and Reciproc systems, regardless of the working length, did not
produce apical microcracks.
PMID- 28416305
TI - Fracture Strength of Endodontically Treated Teeth with Different Access Cavity
Designs.
AB - INTRODUCTION: The purpose of this study was to compare in vitro the fracture
strength of root-filled and restored teeth with traditional endodontic cavity
(TEC), conservative endodontic cavity (CEC), or ultraconservative "ninja"
endodontic cavity (NEC) access. METHODS: Extracted human intact maxillary and
mandibular premolars and molars were selected and assigned to control (intact
teeth), TEC, CEC, or NEC groups (n = 10/group/type). Teeth in the TEC group were
prepared following the principles of traditional endodontic cavities. Minimal
CECs and NECs were plotted on cone-beam computed tomographic images. Then, teeth
were endodontically treated and restored. The 160 specimens were then loaded to
fracture in a mechanical material testing machine (LR30 K; Lloyd Instruments Ltd,
Fareham, UK). The maximum load at fracture and fracture pattern (restorable or
unrestorable) were recorded. Fracture loads were compared statistically, and the
data were examined with analysis of variance and the Student-Newman-Keuls test
for multiple comparisons. RESULTS: The mean load at fracture for TEC was
significantly lower than the one for the CEC, NEC, and control groups for all
types of teeth (P < .05), whereas no difference was observed among CEC, NEC, and
intact teeth (P > .05). Unrestorable fractures were significantly more frequent
in the TEC, CEC, and NEC groups than in the control group in each tooth type (P <
.05). CONCLUSIONS: Teeth with TEC access showed lower fracture strength than the
ones prepared with CEC or NEC. Ultraconservative "ninja" endodontic cavity access
did not increase the fracture strength of teeth compared with the ones prepared
with CEC. Intact teeth showed more restorable fractures than all the prepared
ones.
PMID- 28416306
TI - Histologic Findings of a Human Immature Revascularized/Regenerated Tooth with
Symptomatic Irreversible Pulpitis.
AB - INTRODUCTION: Pulp revascularization/regeneration in immature permanent teeth
with necrotic pulp and/or apical periodontitis is an effective approach for
inducing root maturation. Previous histologic studies showed cementoid/osteoid
tissue and/or periodontal ligament-like tissue formed within the root canals.
This case report describes the histologic findings of a human symptomatic
irreversible pulpitis immature permanent tooth with most of the pulp removed
after a revascularization/regeneration procedure. METHODS: A human immature
permanent mandibular premolar (tooth #29) was diagnosed as symptomatic
irreversible pulpitis with symptomatic apical periodontitis at the emergency
department. Most of the pulp was removed. The tooth was treated with
revascularization/regeneration. RESULTS: At the 12-month recall, the radiographic
examination revealed thickening of the root canal wall, narrowing of the root
apex, and lengthening of the root. The tooth was extracted at 12 months for
orthodontic treatment. The specimens were processed for histologic examination.
Histologically, the apical third of the root canal was filled with newly formed
dentinlike and pulplike tissue. There was a layer of flattened odontoblastlike
cells lining the dentinal wall. In the midportion of the root canal, the newly
formed dentinlike tissue gradually changed to cementumlike tissue. In the upper
third of the root canal, there was a presence of cementocytelike cells housed in
the lacunae of cementumlike tissue around the loose connective tissue.
CONCLUSIONS: In the present case, regeneration of the pulplike tissue and the
periodontium existed after a revascularization/regeneration procedure in an
immature permanent tooth clinically diagnosed as symptomatic irreversible
pulpitis.
PMID- 28416307
TI - The Efficacy of the WaveOne Reciprocating File System versus the ProTaper
Retreatment System in Endodontic Retreatment of Two Different Obturating
Techniques.
AB - INTRODUCTION: This ex vivo study aimed to evaluate the efficacy of retreating
GuttaCore (Dentsply Tulsa Dental Specialties, Tulsa, OK) and warm vertically
condensed gutta-percha in moderately curved canals with 2 different systems:
ProTaper Universal Retreatment (Dentsply Tulsa Dental) and WaveOne (Dentsply
Tulsa Dental). METHODS: Eighty mesial roots of mandibular molars were used in
this study. The mesiobuccal canals in each sample were prepared to length with
the WaveOne Primary file (Dentsply Tulsa Dental). The canals were obturated with
either a warm vertical approach or with GuttaCore and divided into 4 retreatment
groups with the same mean root curvature: warm vertical retreated with ProTaper,
warm vertical retreated with WaveOne, GuttaCore retreated with ProTaper, and
GuttaCore retreated with WaveOne. The warm vertical groups were obturated using a
continuous-wave technique of gutta-percha compaction, and the GuttaCore groups
were obturated according to the manufacturer's instructions. After allowing
sealer to set, each specimen was retreated with either the ProTaper Universal
Retreatment files D1, D2, or D3 or with the WaveOne Primary file to the
predetermined working length. The time taken to reach the working length was
recorded. Instrument fatigue and failure were also evaluated. RESULTS: The post
hoc 2-sample t tests showed that the overall mean total time taken to reach the
working length for the warm vertical groups was significantly greater than that
observed for the GuttaCore groups (mean = 87.11 vs 60.16 seconds, respectively),
and the overall mean total time taken to reach the working length for WaveOne was
significantly greater than that observed for ProTaper (99.09 vs 48.18 seconds,
respectively). Two-way analysis of variance showed a significant main effect for
both the type of experiment groups (F1,76 = 15.32, P = .0002) and the type of
retreatments (F1,76 = 54.67, P < .0001). Also, the WaveOne Primary file underwent
more separations than the ProTaper files. CONCLUSIONS: The WaveOne Primary file
underwent more separations and was unable to remove gutta-percha as efficiently
as the ProTaper Universal Retreatment files. Also, canals obturated with
GuttaCore were retreated more efficiently and with fewer file separations than
the canals obturated using continuous wave of warm gutta-percha.
PMID- 28416308
TI - Implantation of Endothelial Cells with Mesenchymal Stem Cells Accelerates Dental
Pulp Tissue Regeneration/Healing in Pulpotomized Rat Molars.
AB - INTRODUCTION: This study aimed to examine whether the implantation of mesenchymal
stem cells (MSCs) with endothelial cells (ECs) accelerates pulp tissue
regeneration/healing and induces dentin bridge formation in a rat model of molar
coronal pulp regeneration. METHODS: The maxillary first molars of Wistar rats
were subjected to pulpotomy. Then, pulp chambers were implanted with
biodegradable hydrogel-made scaffolds carrying MSCs together or without dermal
microvascular ECs, and the cavities were sealed with mineral trioxide aggregate.
After 14 days, pulp samples were analyzed by immunohistochemistry; messenger RNA
expression of B-cell lymphoma 2 (Bcl-2), chemokine (C-X-C motif) ligand 1
(Cxcl1), CXC receptor 2 (Cxcr2), and dentin sialophosphoprotein (Dspp) by
quantitative polymerase chain reaction, and protein expression of nestin and
vascular endothelial growth factor by Western blotting. RESULTS: Teeth
coimplanted with MSCs and ECs showed pulp healing with complete dentin bridge
formation, whereas those implanted with MSCs alone had incomplete dentin bridges.
Bcl-2, Cxcl1, Cxcr2, and Dspp messenger RNA levels were significantly up
regulated in the pulp of MSC/EC-implanted teeth compared with those in MSC
implanted teeth. Immunohistochemical analysis revealed the expression of nestin
in odontoblastlike cells under dentin bridges in the MSC/EC coimplanted group.
The density of CD31-expressing ECs and the expression of nestin and vascular
endothelial growth factor proteins were significantly up-regulated in the MSC/EC
implanted pulp compared with the MSC-implanted pulp. CONCLUSIONS: The
implantation of ECs with MSCs accelerated pulp tissue regeneration/healing and
dentin bridge formation, up-regulated the expression of proangiogenic factors,
and increased the density of ECs in pulpotomized rat molars.
PMID- 28416309
TI - Detection of Apical Root Cracks Using Spectral Domain and Swept-source Optical
Coherence Tomography.
AB - INTRODUCTION: This study aimed to evaluate the ability of 2 optical coherence
tomographic (OCT) systems to detect apical dentinal microcracks. METHODS: Twenty
extracted human single-rooted mandibular incisors were selected. After root canal
preparation with an R40 Reciproc file (VDW, Munich, Germany), the specimens
presenting apical microcracks were identified using micro-computed tomographic
(micro-CT) scanning as the gold standard. Then, the apical portions of the roots
were imaged with spectral domain OCT (SD-OCT) and swept-source OCT systems, and
the resulting images were blindly evaluated by 3 independent examiners to detect
microcracks. The diagnostic performance of each OCT device was calculated, and
statistical analysis was performed. RESULTS: Based on the micro-CT images, 12
(60%) roots presented dentinal microcracks in the apical region. The images
generated by the OCT systems were able to show microcrack lines at the same
location as the corresponding micro-CT cross sections. Although the diagnostic
performance of the SD-OCT device was superior, there were no statistically
significant differences between the 2 OCT devices (P > .05). Interexaminer
agreement was substantial to almost perfect for the SD-OCT system and moderate to
almost perfect for the swept-source OCT system, whereas intraexaminer agreement
was substantial to almost perfect for both OCT devices. CONCLUSIONS: The
detection ability verified for both OCT systems renders them promising tools for
the diagnosis of apical microcracks.
PMID- 28416310
TI - Cracked Teeth and Poor Oral Masticatory Habits: A Matched Case-control Study in
China.
AB - INTRODUCTION: Previous studies have suggested that masticatory forces are
associated with cracked teeth, but it is not clear which specific poor oral
masticatory habits may be more likely to cause cracks. The aim of this study was
to quantitatively assess risk factors for cracked teeth among poor oral
masticatory habits and create a model for individualized risk predictions.
METHODS: We enrolled 35 patients with cracked teeth matched to 70 controls
without cracked teeth by age, sex, position of the affected tooth,
presence/absence of systemic disease, and diagnosis of symptomatic irreversible
pulpitis from the Stomatology Hospital of Tianjin Medical University, Tianjin,
China. Odds ratios (ORs) were calculated using conditional logistic regression
analysis. RESULTS: Thermal cycling eating habits (OR = 3.296; 95% confidence
interval [CI], 1.684-6.450), eating coarse foods (OR = 2.727; 95% CI, 1.340
5.548), chewing on hard objects (OR = 2.087; 95% CI, 1.041-4.182), and unilateral
mastication (OR = 2.472; 95% CI, 1.255-4.869) were independent risk factors for
cracked teeth. The corresponding risk scores were 2.182, 1.691, 1.467, and 1.589,
respectively. The area under the receiver operating characteristic curve and its
95% CI were 0.920 (0.868-0.973); the sensitivity and specificity were 0.943 and
0.800, respectively. CONCLUSIONS: Thermal cycling eating habits were strongly
associated with cracked teeth, whereas eating coarse foods, chewing on hard
objects, and unilateral mastication were also independent risk factors for
cracked teeth. These findings yield insights into ways to promote the prevention
of risky behaviors for cracked teeth.
PMID- 28416311
TI - Complicated Root Canal Configuration of Mandibular First Premolars Is Correlated
with the Presence of the Distolingual Root in Mandibular First Molars: A Cone
beam Computed Tomographic Study in Taiwanese Individuals.
AB - INTRODUCTION: The purpose of this study was to examine the frequency and
bilateral consistency of distolingual roots (DLRs) in permanent mandibular first
molars (PMFMs) and root canal configurations in PMFPs (permanent mandibular first
premolars) and to determine the correlation between the root canal configurations
of PMFPs with the appearance of DLRs in PMFMs. METHODS: A total of 932 cone-beam
computed tomographic images of PMFMs and PMFPs were collected from 233 patients.
The frequency and bilateral consistency of DLRs in PMFMs along with root canal
configurations (root number and canal number) of PMFPs were recorded and
evaluated ipsilaterally and contralaterally. Multivariable logistic regression
analysis was used to evaluate the correlation between the root canal
configurations of PMFPs with the appearance of DLRs in PMFMs. RESULTS: The
prevalence of PMFMs with DLRs was 24.7%, and the incidence of complicated root
canal configurations of PMFPs was 26.6%. The incidence of complicated root canal
configurations of PMFPs was 19.6% in the non-DLR group, 37.2% in the unilateral
DLR group, and 44.7% in the bilateral DLR group. After adjusting for categoric
variables including sex, age, and side, the odds ratios for the frequency of
complicated root canal configurations of PMFPs in the unilateral DLR and
bilateral DLR groups compared with the non-DLR group were 2.472 (95% confidence
interval, 1.434-4.263; P = .001) and 3.392 (95% confidence interval, 1.976-5.823;
P < .001), respectively. CONCLUSIONS: An increasing and corresponding trend
between the presence of DLRs in PMFMs and complicated root canal configurations
in PMFPs was noted in Taiwanese individuals. These results suggest that the
clinicians should familiarize themselves with the anatomic variants of PMFMs and
PMFPs before endodontic treatment.
PMID- 28416312
TI - Periapical Lesions Increase Macrophage Infiltration and Inflammatory Signaling in
Muscle Tissue of Rats.
AB - INTRODUCTION: Our previous studies have shown that periapical lesions (PLs) in
rats cause systemic disorders such as increased tumor necrosis factor-alpha
plasma levels, insulin resistance, and impairment in insulin signal transduction
in muscle tissue. However, the mechanisms involved in these alterations are not
fully understood. Under chronic inflammatory conditions such as obesity, it has
been shown that the skeletal muscle is affected by inflammation, and the number
of resident macrophages that are associated with impairments of insulin action
and sensitivity is increased. This study aimed to investigate the presence of
macrophages, activation of inflammatory pathways in muscle tissue, glycemia, and
insulinemia of rats with PLs. METHODS: Sixty Wistar rats were distributed into a
control group; a group with 1 PL (1PL), which was induced in the right maxillary
first molar; and a group with 4 PLs (4PL), which were induced in the right upper
and lower first and second molars. We quantified macrophage content by
immunohistochemistry for the F4/80 protein. We evaluated Jun N-terminal kinase
and IKKalpha/beta phosphorylation status in the muscle tissue by Western
blotting. Serum levels of lipopolysaccharide (LPS) and HSP70 and plasma levels of
glucose and insulin were assessed by using commercial kits. RESULTS: The 1PL and
4PL groups showed increase in macrophage content, IKKalpha/beta, and Jun N
terminal kinase phosphorylation status, serum LPS and HSP70 levels, and insulin
resistance and no changes in glycemia and insulinemia compared with the control
group. There was no difference in these parameters between the 1PL and 4PL
groups. CONCLUSIONS: PLs promoted an increase in macrophage infiltration,
activation of inflammatory pathways in muscle tissue, and serum concentrations of
HSP70 and LPS in rats. The present study improves the knowledge on the impact of
oral inflammations on the development of systemic alteration, which can induce
insulin resistance.
PMID- 28416313
TI - Changes of Periodontal Parameters after Apical Surgery: Correlation of Clinical
and Cone-beam Computed Tomographic Data.
AB - INTRODUCTION: The purpose of this study was to evaluate the changes of the
marginal periodontium 1 year after apical surgery. METHODS: Clinical and
radiographic (cone-beam computed tomographic) examinations of 54 teeth treated
with buccal access flaps for apical surgery were performed at baseline and after
1 year. Clinical assessment included measurements of probing pocket depth, the
level of gingival margin (GM), and the width of keratinized tissue. Subsequently,
the clinical attachment level (CAL) and the width of the attached gingiva were
calculated. On bucco-oral cone-beam computed tomographic sections, the height and
thickness of the crestal bone and the thickness of the alveolar bone were
measured at different levels. RESULTS: In general, the calculated mean changes of
periodontal tissue and crestal/alveolar bone were only minimal. Significant mean
changes included only GM and CAL on midoral aspects and the distance from the
cementoenamel junction or restoration margin on midbuccal sites. CAL was further
correlated with the thickness of the alveolar bone at 3 mm below the
cementoenamel junction or restoration margin. None of the clinically and
radiographically calculated mean changes were correlated with sex, biotype, or
incision techniques. With regard to age, older patients showed significantly more
gingival recession on the buccal aspect compared with younger individuals.
Furthermore, mean changes of the midbuccal width of the attached gingiva were
positively correlated with the healing outcome, whereas mean changes of the
midoral GM and CAL were negatively correlated with the healing outcome.
CONCLUSIONS: Within an observation period of 1 year, the marginal periodontium
and its underlying bone structures did not suffer from significant changes after
apical surgery.
PMID- 28416314
TI - The Use of a Novel Approach for the Instrumentation of a Cone-beam Computed
Tomography-discernible Lateral Canal in an Unusual Maxillary Incisor: Case
Report.
AB - Lateral and apical ramifications of the main root canal create potential pathways
through which bacteria can spread and remain unaffected by treatment procedures.
It is a challenge for the specialty to find techniques that can predictably
reach, disinfect, and obturate these ramifications. Here, we report the use of a
novel instrumentation approach to aid in the negotiation and management of a
lateral canal discernible on cone-beam computed tomography (CBCT) in an unusual
maxillary central incisor. A 23-year-old female patient was referred for
evaluation and possible treatment of tooth 9. The periapical radiographic
examination revealed pulp chamber obliteration, existence of a lateral lesion,
and a possible complex internal root canal anatomy. The CBCT evaluation revealed
the existence of a lateral lesion, a periapical lesion, an additional
distopalatal canal, and a lateral canal exiting at the lateral lesion. The
diagnosis of asymptomatic apical and lateral periodontitis of tooth 9 was
reached. CBCT-aided access cavity preparation and scouting resulted in the
successful negotiation of all canals, main and lateral. A novel instrumentation
technique with precurved controlled memory files was used for the mechanical
preparation of the lateral canal to a 25/04 enlargement. Obturaton of the lateral
canal was achieved with a single gutta-percha cone and AH Plus Root Canal Sealer.
At the 2-year follow-up, the patient was asymptomatic, and the 2-dimensional
radiographic examinations revealed resolution of both the periapical and the
lateral lesions. This case report describes the application of a novel
instrumentation technique for the mechanical debridement of an infected lateral
canal discernible on CBCT and reinforces the importance of treating the root
canals as systems that possesses anatomic intricacies that need to be addressed.
PMID- 28416315
TI - Preparation of Oval-shaped Canals with TRUShape and Reciproc Systems: A Micro
Computed Tomography Study Using Contralateral Premolars.
AB - INTRODUCTION: The purpose of this study was to compare the shaping properties of
TRUShape and Reciproc systems during preparation of oval-shaped canals from
contralateral teeth by using micro-computed tomography scanning. METHODS:
Thirteen pairs of freshly extracted contralateral mandibular premolars with a
single oval-shaped canal were selected and divided into 2 groups according to the
root canal instrumentation technique, TRUShape and Reciproc. The final apical
size of instrumentation was 40/.06 for both systems. Data were statistically
analyzed for the increase in canal volume and surface area and the amount of
unprepared areas promoted by the 2 systems. RESULTS: Preparation with both
systems significantly increased the volume and area of the canals (P < .001),
with no significant differences between them (P > .05). When the full canal
length was evaluated, the amount of uninstrumented areas was significantly larger
for Reciproc (30%) than TRUShape (24%) (P < .05). However, analysis restricted to
the apical 4-mm segment revealed no statistically significant difference in
untouched areas (25% for Reciproc and 20% for TRUShape) (P > .05). CONCLUSIONS:
Both instrument systems behaved similarly in promoting the increase of root canal
volume and surface area. When the full canal length was evaluated, TRUShape
instruments showed less unprepared areas than Reciproc. However, this difference
did not occur for the apical part of the root canal. None of the techniques could
completely prepare oval-shaped root canals.
PMID- 28416316
TI - Effect of Passive Ultrasonic Activation on Organic Tissue Dissolution from
Simulated Grooves in Root Canals Using Sodium Hypochlorite with or without
Surfactants and EDTA.
AB - INTRODUCTION: The aim of this study was to evaluate the porcine palatal mucosa
dissolution from artificial grooves using a final rinse with sodium hypochlorite
(NaOCl) with or without a surfactant or ultrasonic activation (PUI). METHODS: The
root canals of 130 human maxillary central incisors were chemomechanically
prepared and the teeth split. A standardized longitudinal intracanal groove was
created in 1 of the root halves. One hundred thirty porcine palatal mucosa
samples were collected, adapted in order to fit into the grooves, and weighed.
The reassembled specimens were randomly divided in 3 experimental groups (n = 40)
based on their irrigation protocol (ie, positive pressure [PP] and PUI during 15
[PUI-15] or 30 seconds [PUI-30]) and divided in subgroups according to the NaOCl
preparation used: Vista 6% plain (Vista Dental Products, Racine, WI) or Chlor
XTRA (Vista Dental Products) (containing surfactant). An EDTA intermediate rinse
was included. Palatal mucosa weights were measured after the assays. The
intergroup weight changes were statistically analyzed. RESULTS: Complete
dissolution did not occur in any sample. Chlor-XTRA subgroups were associated
with increased weight reduction compared with Vista 6% plain subgroups; however,
the differences were significant (P < .05) only for PP and PUI-15. PUI-30
increased weight reduction compared with PP for both hypochlorites and PUI-15
using Vista 6% plain (P < .05). PUI-30 with Vista 6% plain performed
significantly better than PP with Chlor-XTRA (P < .05). CONCLUSIONS: The addition
of a surfactant to NaOCl and/or PUI activation increased palatal mucosa
dissolution within artificial grooves in the root canal of incisor teeth. PUI
agitation was often able to compensate for the absence of surfactants.
PMID- 28416317
TI - Zinc Oxide Inhibits Dental Discoloration Caused by White Mineral Trioxide
Aggregate Angelus.
AB - INTRODUCTION: The aim of the study was to investigate the addition of variable
amounts of zinc oxide to inhibit dental discoloration caused by mineral trioxide
aggregate (MTA) Angelus. METHODS: MTA Angelus and MTA with additions of 5%, 15%,
and 45% zinc oxide (ZnO) in weight were tested. The set cements were
characterized by using a combination of scanning electron microscopy, energy
dispersive spectroscopy, and x-ray diffraction. Radiopacity and setting time were
analyzed according to American National Standards Institute/American Dental
Association (57/2012) and American Society for Testing and Materials (C266-08).
Volume change was evaluated by using micro-computed tomography analysis. The pH
and calcium ion release were measured after 3 hours, 24 hours, and 28 days.
Dental discoloration in contact with the cements was measured after 24 hours, 28
days, and 90 days. Biocompatibility to subcutaneous implantation in rats was
verified after 30 and 60 days. RESULTS: Addition of ZnO did not alter
significantly the radiopacity, setting time, volume change, pH, and
biocompatibility compared with MTA Angelus (P > .05). Calcium ion release
increased with addition of ZnO (P < .05). Proportions of 15% and 45% ZnO
interfered in hydration. The 5% ZnO addition was sufficient to prevent the dental
discoloration observed with MTA Angelus. CONCLUSIONS: The addition of 5%, 15%, or
45% zinc oxide to MTA Angelus inhibits dental discoloration without modifying the
radiopacity, setting time, volume change, pH, and biocompatibility.
PMID- 28416318
TI - Basic Fibroblast Growth Factor Regulates Gene and Protein Expression Related to
Proliferation, Differentiation, and Matrix Production of Human Dental Pulp Cells.
AB - INTRODUCTION: Basic fibroblast growth factor (bFGF) plays differential effects on
the proliferation, differentiation, and extracellular matrix turnover in various
tissues. However, limited information is known about the effect of bFGF on dental
pulp cells. The purposes of this study were to investigate whether bFGF
influences the cell differentiation and extracellular matrix turnover of human
dental pulp cells (HDPCs) and the related gene and protein expression as well as
the role of the mitogen-activated protein kinase (MEK)/extracellular-signal
regulated kinase (ERK) signaling pathway. The expression of fibroblast growth
factor receptors (FGFRs) in HDPCs was also studied. METHODS: The expression of
FGFR1 and FGFR2 in HDPCs was investigated by reverse-transcription polymerase
chain reaction. HDPCs were treated with different concentrations of bFGF. Cell
proliferation was evaluated using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl
tetrazolium bromide assay. Cell differentiation was evaluated using alkaline
phosphatase (ALP) staining. Changes in messenger expression of cyclin B1 and
tissue inhibitor of metalloproteinase (TIMP) 1 were determined by reverse
transcription polymerase chain reaction. Changes in protein expression of cdc2,
TIMP-1, TIMP-2, and collagen I were determined by Western blotting. U0126 was
used to clarify the role of MEK/ERK signaling. RESULTS: HDPCs expressed both
FGFR1 and FGFR2. Cell viability was stimulated by 50-250 ng/mL bFGF. The
expression and enzyme activities of ALP were inhibited by 10-500 ng/mL bFGF. At
similar concentrations, bFGF stimulates cdc2, cyclin B1, and TIMP-1 messenger RNA
and protein expression. bFGF showed little effect on TIMP-2 and partly inhibited
collagen I expression of pulp cells. U0126 (a MEK/ERK inhibitor) attenuated the
bFGF-induced increase of cyclin B1, cdc2, and TIMP-1. CONCLUSIONS: bFGF may be
involved in pulpal repair and regeneration by activation of FGFRs to regulate
cell growth; stimulate cdc2, cyclin B1, and TIMP-1 expression; and inhibit ALP.
These events are partly associated with MEK/ERK signaling.
PMID- 28416320
TI - Predictive Value of Using Initial Versus Terminal Deceased Donor Creatinine to
Calculate the Kidney Donor Risk Index.
PMID- 28416319
TI - Feasibility of Cone-beam Computed Tomography in Detecting Lateral Canals before
and after Root Canal Treatment: An Ex Vivo Study.
AB - INTRODUCTION: The study objective was to evaluate the effectiveness of cone-beam
computed tomographic (CBCT) imaging for the detection of lateral canals (LCs) in
endodontically treated premolars. METHODS: Two evaluators classified 80 extracted
premolars into 2 groups based on the absence (n = 40) or presence (n = 40) of LCs
according to micro-computed tomographic analysis. The extracted teeth were
fixated in a human mandible and scanned with CBCT imaging. Subsequently, each
tooth was endodontically treated, and CBCT scans were repeated. Three experienced
examiners evaluated all images randomly. Receiver operating characteristic curves
were compared using the McNemar test, and sensitivity, specificity, positive
predictive value, and negative predictive value (NPV) were obtained. RESULTS: The
area under the receiver operating characteristic curve values were 0.58 and 0.49
before and after root canal treatment, respectively. These values were
statistically significantly different (P < .001). Before root canal treatment
sensitivity, specificity, positive predictive value, and negative predictive
value were 55%, 52%, 55%, and 56%, whereas after root canal treatment the values
were 33%, 61%, 46%, and 48%, respectively. CONCLUSIONS: LC detection in
nontreated teeth presented low accuracy, whereas among treated teeth CBCT imaging
showed no efficacy. The results suggest that CBCT imaging is not an effective
diagnostic tool for LC detection.
PMID- 28416321
TI - Targeted Deprescribing in an Outpatient Hemodialysis Unit: A Quality Improvement
Study to Decrease Polypharmacy.
AB - BACKGROUND: Polypharmacy in hemodialysis patients can result in adverse patient
outcomes. Deprescribing tools can reduce polypharmacy, yet no method exists for
an outpatient hemodialysis population. DESIGN: Quality improvement study. SETTING
& PARTICIPANTS: 240 patients in a tertiary-care outpatient hemodialysis unit.
QUALITY IMPROVEMENT PLAN: We aimed to: (1) develop a deprescribing tool for
target medications with poor evidence for efficacy and safety, (2) determine its
effectiveness in decreasing polypharmacy, and (3) monitor patient safety and
satisfaction. OUTCOMES: The primary outcome was the proportion of target
medications completely deprescribed after 4 weeks. Secondary outcomes were the
proportion of target medications completely deprescribed after 6 months, average
number of medications per patient before and after deprescription, and proportion
of successful deprescriptions for each target medication. MEASUREMENTS: Number of
medications deprescribed at 4 weeks and 6 months. Patient safety and satisfaction
were monitored using drug-specific monitoring parameters. RESULTS: A
deprescribing tool for specific medications was developed and implemented in the
hemodialysis unit. 5 medication classes were selected: quinine, diuretics, alpha1
blockers, proton pump inhibitors, and 3-hydroxy-3-methylglutaryl-coenzyme A
reductase inhibitors (statins). All 240 patients in the unit were screened using
the deprescribing tool. There were 171 of 240 (71%) patients prescribed at least
1 of the 5 target medications, and after applying the tool, 35 of 40 (88%)
eligible patients had the medications deprescribed. There were 31 of 40 (78%)
target medications completely deprescribed. 6 months after the study, only 5 of
31 (16%) medications discontinued were represcribed. At the end of the study, 57%
of patients were taking fewer medications than at baseline. No adverse events
were observed. LIMITATIONS: Single-center study that relied on patient self
reporting of medication use and adherence to our recommendations. CONCLUSIONS:
Deprescribing tools can be applied successfully in an outpatient hemodialysis
unit to reduce polypharmacy while maintaining patient safety and satisfaction.
PMID- 28416322
TI - Nephrologists and Integrated Kidney Disease Care: Roles and Skills Essential for
Nephrologists for Future Success.
AB - As the costs of caring for patients with end-stage renal disease have grown, so
has the pressure to provide high-quality care at a lower cost. Prompted in large
part by regulatory and legislative changes, reimbursement is shifting from a fee
for-service environment to one of value-based payment models. Nephrologists in
this new environment are increasingly responsible not only for direct patient
care, but also for population management and the associated clinical outcomes for
this vulnerable population. This Perspective article aims to recognize the key
role and skills needed in order to successfully practice within these new value
based care models. The new paradigm of delivering and financing care also
presents opportunities for nephrologists to shape how care is delivered, define
meaningful quality metrics, and share in the financial outcomes of these
approaches. Though it will take time, the training and mind-set of nephrologists
must evolve to accommodate these expanded practice expectations required by a
system that demands measurement, reporting, accountability, and improvement, not
only for individuals but also for populations of patients.
PMID- 28416323
TI - Review of coronary subclavian steal syndrome.
AB - The clinical benefits of using the left internal mammary artery (LIMA) to bypass
the left anterior descending artery are well established making it the most
frequently used conduit for coronary artery bypass surgery (CABG). Coronary
subclavian steal syndrome (CSSS) occurs during left arm exertion when (1) the
LIMA is used during bypass surgery and (2) there is a high grade (>=75%) left
subclavian artery stenosis or occlusion proximal to the ostia of the LIMA
resulting in "stealing" of the myocardial blood supply via retrograde flow up the
LIMA graft to maintain left upper extremity perfusion. Although CSSS was once
thought to be a rare phenomenon, its prevalence has been underestimated and is
becoming increasingly recognized as a serious threat to the success of CABG.
Current guidelines are lacking on recommendations for screening of subclavian
artery stenosis (SAS) pre- and post-CABG. We hope to provide an algorithm for SAS
screening to prevent CSSS in internal mammary artery bypass recipients and review
treatment options in the percutaneous era.
PMID- 28416324
TI - E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2.
AB - Adipogenesis is mediated by glucocorticoids via transcriptional regulation of
glucocorticoid receptor (GR) target genes. However, the mechanism by which GR
participates in adipogenesis has hitherto been poorly characterized. In this
study, E4 promoter-binding protein 4 (E4BP4) was found to have a critical role in
adipogenic differentiation of preadipocytes. Gain-of-function and loss-of
function studies revealed that E4BP4 acts as a positive regulator of adipogenesis
in 3T3-L1 cells. E4BP4 was markedly induced by glucocorticoid (dexamethasone) via
GR and cAMP response element-binding protein (CREB) during adipogenesis.
Knockdown of E4BP4 abolished dexamethasone-induced adipogenesis, and
overexpression of E4BP4 partially accounted for the actions of dexamethasone in
adipogenic differentiation. Promoter deletion analysis confirmed that E4BP4
transcriptionally represses COX2 promoter activity, whereas COX2 overexpression
reversed the acceleration of E4BP4 in adipogenesis. Thus, E4BP4 acts as a key pro
adipogenic transcription factor by trans-repressing COX2 in glucocorticoid
associated adipocyte differentiation.
PMID- 28416325
TI - Involvement of the nuclear progestin receptor in LH-induced expression of
membrane type 2-matrix metalloproteinase required for follicle rupture during
ovulation in the medaka, Oryzias latipes.
AB - Hormonal regulation of the expression of Mmp15, a proteolytic enzyme
indispensable for ovulation in the teleost medaka, was investigated. In an in
vitro culture system using preovulatory follicles, Mmp15 expression and ovulation
were induced in the presence of recombinant luteinizing hormone (rLh). Both rLh
induced Mmp15 expression and ovulation were 17alpha, 20beta-dihydroxy-4-pregnen-3
one-dependent, suggesting the involvement of a nuclear progestin receptor (Pgr).
In vitro follicle ovulation and Mmp15 expression were reduced by treatment with
the Pgr antagonist RU-486. Like Pgr, the transcription factor CCAAT/enhancer
binding protein beta (Cebpb) was induced by rLh. ChIP analyses indicated that Pgr
and Cebpb bound to the mmp15 promoter region. These results indicate that the rLh
induced expression of Mmp15 is mediated by Pgr and Cebpb. A differential timing
of expression of Pgr and Cebpb in the preovulatory follicles appears to explain
the considerably long time-lag from the pgr gene activation to mmp15 gene
expression.
PMID- 28416326
TI - Reply to comment on "Combination of cupric ion with hydroxylamine and hydrogen
peroxide for the control of bacterial biofilms on RO membranes by Hye-Jin Lee,
Hyung-Eun Kim, Changha Lee [Water Research 110, 2017, 83-90]".
PMID- 28416328
TI - Hepatoprotective Mongolian prescription II enhances the antitumor effects of
chemotherapeutics in hepatocellular carcinoma xenografts.
AB - Hepatoprotective Mongolian prescription II (MPII), a mixture of 18 different
medicinal herbs, significantly inhibited the growth of human liver cancer cell
lines Huh-7 and HepG2 in vitro with different concentrations; MPII (6mg/mL)
inhibited cell proliferation by 80.48%. MPII induced apoptosis in both cell
lines, which was observed by light microscopy and flow cytometry. MPII-induced
apoptosis and G0/G1 cell cycle arrest were quantified by Annexin V-FITC/PI
staining and flow cytometry. At the molecular level, MPII induced caspase-3,
caspase-8, caspase-9, and cytochrome c gene expression. In vivo, MPII
dramatically inhibited human liver tumor growth in a xenograft model in Kunming
mice with no apparent cytotoxicity to the hosts. Apoptotic genes (Bcl-2 and Bax)
are up-regulated, suggesting that the ratio of Bcl-2/Bax was statistically
significant, indicating that the drugs had affected the expression of apoptosis
genes, especially on induce apoptosis gene Bax. We also observed an attenuated
effect when MPII was used in combination with chemotherapy drug 5-fluorouracil (5
FU). The mice treated with 5-FU alone did not show a concentration-dependent
effect, but 5-FU in combination with MPII displayed concentration-dependent
effects on liver cancer cells. Our study suggests that MPII works by inducing
apoptosis and cell cycle arrest, and has the potential to be a powerful
anticancer agent.
PMID- 28416330
TI - Delayed responses of subthalamic nucleus to deep brain stimulation in patients
with Parkinson's disease.
PMID- 28416331
TI - A novel inflow cannulation strategy for pediatric mechanical circulatory support
in small left ventricles.
PMID- 28416329
TI - Weight stigma predicts inhibitory control and food selection in response to the
salience of weight discrimination.
AB - OBJECTIVE: Fear and stigmatization are often used to motivate individuals with
higher body weight to engage in healthy behaviors, but these strategies are
sometimes counterproductive, leading to undesirable outcomes. In the present
study, the impact of weight-based stigma on cognition (i.e., inhibitory control)
and food selection (i.e., calories selected) was examined among individuals who
consider themselves to be overweight. It was predicted that participants higher
in perceived weight stigma would perform more poorly on an inhibitory control
task and order more calories on a food selection task when they read about
discrimination against individuals with higher weight versus discrimination
against an out-group. METHODS: Participants completed online prescreen measures
assessing whether they considered themselves to be overweight and their
perceptions of weight stigma. Individuals who considered themselves to be
overweight were invited into the laboratory to complete tasks that manipulated
weight-based discrimination, then inhibitory control and food selection were
measured. RESULTS: The higher participants were in perceived weight stigma, the
more poorly they performed on the inhibitory control task and the more calories
they ordered when they read about discrimination against individuals with higher
body weight. These relationships were not observed when participants read about
discrimination against an out-group. CONCLUSIONS: The present findings provide
evidence that perceptions of weight stigma are critical in understanding the
impact of weight-based discrimination. Additionally, these results have
theoretical and practical implications for both understanding and addressing the
psychological and physical consequences of weight-based stigma.
PMID- 28416327
TI - Executive functioning and substance use in adolescence: Neurobiological and
behavioral perspectives.
AB - The current review is guided by the theoretical perspective that emphasizes the
regulating role of executive functioning (Carver et al., 2009) and presents
studies that elucidate the ways that executive functioning (inhibition and
working memory) explain individual differences in adolescent substance use
independently or by regulating the reactive system (reward and punishment
sensitivity). Behavioral studies indicate that main effects of executive
functioning on adolescent substance use are often nonsignificant or weak in
effect sizes. In contrast, emerging evidence suggests consistent and stronger
regulating effects of executive functioning over reward and punishment
sensitivity. Functional neuroimaging studies reveal significant associations
between executive functioning task-related hemodynamic responses and substance
use with strong effect sizes. There is also direct evidence from studies testing
statistical interactions of the regulating effects of EF-related brain
activation, and indirect evidence in studies examining functional connectivity,
temporal discounting, and reinforced control. We note key future directions and
ways to address limitations in existing work.
PMID- 28416332
TI - The promise of placental power.
PMID- 28416333
TI - Go deep! Benefits of a deep freeze during distal aortic repair.
PMID- 28416334
TI - A systematic approach to improve the outcomes of type A aortic dissection.
AB - OBJECTIVES: The aims of this study are to evaluate the outcomes and trends of
contemporary emergency surgery for acute type A aortic dissection on the basis of
a systematic approach and to assess the impact of temporary aortic crossclamping
during systemic cooling on early and late outcomes. METHODS: We retrospectively
reviewed 702 consecutive patients who underwent emergency surgery for acute type
A aortic dissection between March 2004 and May 2015. Our clinical protocol
includes rapid transfer to the operating room, quick establishment of
cardiopulmonary bypass, temporary aortic crossclamping during cooling, primary
entry resection, and open distal anastomosis. We analyzed the perioperative data,
survival, freedom from aortic reinterventions, and impact of aortic crossclamping
on early and late outcomes. RESULTS: The median time from hospital arrival to
cardiopulmonary bypass establishment was 115 minutes and has decreased over the
last decade (trend test P < .001). We perfused the femoral artery in 615 patients
(87.6%), placed aortic crossclamping in 616 patients (87.7%), and performed open
distal anastomosis in all patients. The operative mortality was 5.4% (38/702),
and the incidence of stroke was 10.8% (76/702). The 7-year overall survival and
freedom from aortic reinterventions were 80.4% and 87.5%, respectively. Compared
with the nonclamping group, the crossclamping group had a shorter operation time,
similar operative mortality, incidence of stroke, and freedom from aortic
reinterventions. CONCLUSIONS: Emergency surgery for acute type A aortic
dissection based on our systematic approach demonstrated excellent early and late
outcomes. The temporary aortic crossclamping during cooling decreased the
operation time without increasing early and late adverse events.
PMID- 28416335
TI - Clinical outcomes following self-expanding metal stent placement for esophageal
salvage.
AB - OBJECTIVES: To assess the efficacy of self-expanding metal stents (SEMS) for
esophageal salvage in patients who would otherwise require esophageal/conduit
resection. METHODS: We performed a retrospective chart review of patients who had
SEMS placed from January 2010 to December 2015. Patient demographics, esophageal
stent characteristics, and outcomes were assessed in our patient cohort. RESULTS:
Our study included a total of 83 patients. A total of 148 SEMS were placed, with
121 partially covered SEMS (pcSEMS) and 27 fully covered SEMS (cSEMS). A stent
was placed more than once in 42.2% of the patients. Median duration of stent
placement was 23 days. Indications for SEMS placement included esophageal leak
after esophageal resection (45.8%), spontaneous esophageal perforation (22.9%),
iatrogenic esophageal perforation (20.5%), and esophageal obstruction (9.6%).
Complications from SEMS placement included 6 stent migrations and 1 esophageal
perforation. Of the 6 stents that migrated, 2 were pcSEMS and 4 were cSEMS. In a
patient who underwent stent placement for a stricture refractory to dilation, a
perforation at the distal end was discovered 2 days after stent removal. The
perforation healed after the second SEMS placement. Ultimately, 15 patients
(18.1%) had to undergo a subsequent esophagectomy or takedown of their conduit
with an overall 81.9% salvage of native esophagus or conduits. CONCLUSIONS: Our
study demonstrates the successful use of SEMS in patients with anastomotic leaks,
perforations, and recalcitrant strictures.
PMID- 28416336
TI - Double trouble or singular success: What can we expect from anatomic correction
of congenitally corrected transposition of the great arteries?
PMID- 28416337
TI - Operating on lungs and thinking on hearts.
PMID- 28416338
TI - Separation and purification of polyphenols from red wine extracts using high
speed counter current chromatography.
AB - Polyphenols are important compounds of red wine owing to their contribution to
sensory properties and antioxidant activities. In this study, high-speed counter
current chromatography (HSCCC) coupled with semi-preparative HPLC was used for
large-scale separation and purification of polyphenols from red wine extracts.
With the solvent system of hexane-ethyl acetate-water (1-50-50), various
oligomeric procyanidins including monomer catechin, epicatechin, dimers B1, B2;
phenolic acids including coutaric acid, caftaric acid and other type of
polyphenols were largely separated within 370min and most of these compounds
presented high yields (0.97mg to 13.79mg) with high purity (90.34% to 98.91%)
after the semi-preparative HPLC isolation. Using the solvent system of Methyl
tert-Butyl Ether (MTBE) - n-butyl alcohol- acetonitrile-water (1-40-1-50,
acidified with 0.01% trifluoroacetic acid (TFA)) by one-step HSCCC of 100mg of
the red wine extracts, the major anthocyanins, i.e., malvidin-3-O-glucoside,
delphinidin-3-O-glucoside and peonidin-3-O-glucoside, as well as two polymeric
proanthocyanidin fractions were successfully separated one another within 320min.
The yields of malvidin-3-O-glucoside, delphinidin-3-O-glucoside and peonidin-3-O
glucoside were 12.12mg, 1.78mg and 11.57mg with the purity of 92.74%, 91.03% and
91.21%, respectively. Thiolysis-UPLC analysis indicated that the two polymeric
proanthocyanidin fractions presented high purity, with mean degree of
polymerization of 7.66+/-0.12 and 6.20+/-0.09, respectively. The further
experiments on the antioxidant activities by DPPH radical test, FRAP assay and
ABTS method showed that all of the isolated procyandins and anthocyanins and the
two polymeric proanthocyanidin fractions, with exception of phenolic acids
possessed much greater antioxidant activities compared to standard Trolox andl
ascorbic acid (2-14 times).
PMID- 28416339
TI - Hemorrhagic cyst of the canal of Nuck after vaginal delivery presenting as a
painful inguinal mass in the early postpartum period.
PMID- 28416340
TI - Use of the Dilapan-S osmotic dilator in missed miscarriage in patients with
severe comorbidities.
PMID- 28416341
TI - The role of cannabinoids in dermatology.
PMID- 28416342
TI - Long-term safety and tolerability of apremilast in patients with psoriasis:
Pooled safety analysis for >=156 weeks from 2 phase 3, randomized, controlled
trials (ESTEEM 1 and 2).
AB - BACKGROUND: Randomized, controlled trials demonstrated efficacy and safety of
apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.
OBJECTIVE: Assess long-term safety of oral apremilast in psoriasis patients.
METHODS: Safety findings are reported for 0 to >=156 weeks from the Efficacy and
Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.
RESULTS: The 0 to >=156-week apremilast-exposure period included 1184 patients
treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to
<=52 weeks, the adverse events (AEs) that occurred in >=5% of patients included
diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension
headache, and headache. From 0 to >=156 weeks, no new AEs (affecting >=5% of the
population) were reported. AEs, serious AEs, and study drug discontinuations
caused by AEs did not increase with long-term exposure. During the 0 to >=156
week period, the rates of major cardiac events (exposure-adjusted incidence rate
[EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years),
depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100
patient-years) did not increase in comparison with the rates found during the 0
to <=52-week period. No serious opportunistic infections, reactivation of
tuberculosis, or clinically meaningful effects on laboratory measurements were
reported. LIMITATIONS: This study had a high dropout rate (21% of patients
ongoing >156 weeks); most were unrelated to safety concerns. CONCLUSIONS:
Apremilast demonstrated an acceptable safety profile and was generally well
tolerated for >=156 weeks.
PMID- 28416343
TI - Pigmented epithelioid melanocytoma (animal-type melanoma): An institutional
experience.
AB - BACKGROUND: Pigmented epithelioid melanocytoma (PEM) is an uncommon, recently
described entity with unknown biologic behavior. There is a high rate of regional
metastases, but limited evidence of distant metastases or disease-related death.
OBJECTIVE: We sought to report our series of patients given a diagnosis of PEM at
our institution and provide mutational analysis of genes commonly implicated in
melanoma in 2 cases. METHODS: The pathology database was queried for cases of PEM
diagnosed at the University of Rochester. Charts were reviewed for follow-up
information. Mutational analysis of melanoma-associated genes was performed on 2
cases. RESULTS: Nine cases of PEM were retrieved in a 10-year retrospective
review. Five patients underwent sentinel lymph node biopsy with 3 of 5 having a
positive sentinel lymph node. All 9 patients are alive and disease-free with
average follow-up of 38.75 months. Two tumors were tested for common melanoma
associated mutations, and were negative, except for a telomerase reverse
transcriptase promoter deletion detected in 1 sample. The deletion has not been
associated with melanoma, and therefore its biologic significance is unclear.
LIMITATIONS: Small sample size, retrospective nature, and single institution
experience are limitations. CONCLUSIONS: PEM appears to have an indolent
behavior. However, currently the evidence is too limited to provide insight into
its true biologic potential.
PMID- 28416344
TI - 25-Hydroxyvitamin-D3 serum modulation after use of sunbeds compliant with
European Union standards: A randomized open observational controlled trial.
AB - BACKGROUND: Regular use of sunbed exposure has been reported to increase 25
hydroxyvitamin-D3 [25(OH)D] serum levels. However, the influence of sunbeds
compliant with the recent European Union standard EN-60335-2-27 on 25(OH)D serum
levels is unknown. OBJECTIVE: We investigated the impact of standard sunbed use
compliant with the European Union standard on 25(OH)D serum modulation and well
being. METHODS: In a randomized controlled study, 25(OH)D serum levels were
measured at enrollment, after 1 week, and after completion of the 12-week period
of sunbed use with twice weekly exposure and compared with the control group
without any sunbed exposure. RESULTS: In the sunbed intervention group (N = 31),
a 27% increase of mean 25(OH)D levels was noted 1 week after starting sunbed use
(P < .01). However, after 12 weeks, mean 25(OH)D levels had declined and were no
longer different from baseline (P = .06). After 12 weeks, 25(OH)D levels did not
differ between the intervention and control group (P = .36). Also the 5-item
World Health Organization Well-Being Index score did not differ between the
sunbed and control groups (P = .19). LIMITATIONS: For ethical reasons recruitment
was limited to persons actively seeking sunbed exposure. CONCLUSIONS: Standard
use of sunbeds compliant with the European Union standard induced a transient
increase of 25(OH)D levels, whereas no change in well-being was observed.
PMID- 28416345
TI - Laryngeal function-preserving operation for T4a laryngeal cancer with vocal cord
paralysis - A case report.
AB - For locally advanced laryngeal cancers, the standard treatment of choice is
chemoradiotherapy if organ function needs to be conserved. Surgical treatment
with larynx preservation is conducted only for limited cases. For locally
advanced laryngeal cancers such as those with vocal cord fixation and/or cricoid
cartilage destruction, there is no apparent standardized organ-preserving surgery
keeping the essential laryngeal functions, viz. the airway, deglutition and
articulation, uncompromized. Recently, our surgical team saw a patient with T4a
advanced laryngeal cancer with vocal cord fixation who aspired to maintain his
laryngeal function. Driven by his eagerness, we contrived novel techniques for
laryngeal function preservation and performed a two-staged operation. In the
first stage, extended vertical partial laryngectomy was conducted including
resection of the affected thyroid, arytenoid, and cricoid cartilages, followed by
local closure of the hypopharynx. Additionally, laryngeal suspension surgery and
cricopharyngeal myotomy were performed in addition to suturing the epiglottis
with the intact arytenoid cartilage to enhance swallowing function. In the second
stage, airway reconstruction was performed using a local skin flap. As of 10
months after operation, there has been no tumor recurrence, and the reconstructed
larynx has been working satisfactorily. In this report we describe an innovative
operation that was especially contrived for laryngeal function preservation.
PMID- 28416346
TI - Bilateral spontaneous symptomatic temporomandibular joint herniation into the
external auditory canal: A case report and literature review.
AB - Spontaneous temporomandibular joint (TMJ) herniation is the entity of protrusion
of the retrodiscal contents of the TMJ into the external auditory canal (EAC)
through a persistent Huschke's foramen. There have been a number of reports of
spontaneous TMJ herniation, but there are no reports of bilateral symptomatic TMJ
herniation. We report a case of a 70-year-old man who complained of a crunching
sound in both ears during mastication. Examination showed bulging from the
anterosuperior wall of the EAC on each side when the patient opened his mouth,
which pushed the tympanic membrane medially. Bony defects in the corresponding
area were seen on computed tomography. We describe a very rare case of bilateral
spontaneous TMJ herniation that caused symptoms by having a direct impact on the
tympanic membrane.
PMID- 28416347
TI - Blood collection vials and clinically used intravenous fluids contain significant
amounts of nitrite.
AB - The biology of the inorganic anion nitrite is linked to nitric oxide (NO) as
nitrite can be reduced to NO and mediate its biological activities. Thus, studies
of nitrite biology require sensitive and selective chemical assays. The acetic
and ascorbic acids method is selective for nitrite and measures it in biological
matrices. However, one of the pitfalls of nitrite measurements is its ubiquitous
presence in sample collection tubes. Here, we showed high levels of nitrite in
collection tubes containing EDTA, sodium citrate or sodium heparin and smaller
amounts in tubes containing lithium heparin or serum clot activator. We also
showed the presence of nitrite in colloid and crystalloid solutions frequently
administered to patients and found variable levels of nitrite in 5% albumin, 0.9%
sodium chloride, lactated ringer's, and dextrose-plus-sodium chloride solutions.
These levels of nitrite varied across lots and manufacturers of the same type of
fluid. Because these fluids are administered intravenously to patients (including
those in shock), sometimes in large volumes (liters), it is possible that
infusions of these nitrite-containing fluids may have clinical implications. A
protocol for blood collection free of nitrite contamination was developed and
used to examine nitrite levels in whole blood, red blood cells, plasma and urine
from normal volunteers. Nitrite measurements were reproducible, had minimal
variability, and did not indicate sex-differences. These findings validated a
method and protocol for selective nitrite assay in biological fluids free of
nitrite contamination which can be applied for study of diseases where
dysfunctional NO signaling has been implicated.
PMID- 28416348
TI - Respiratory function in facioscapulohumeral muscular dystrophy 1.
AB - To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk
factors for developing respiratory insufficiency in facioscapulohumeral muscular
dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1
of varying degrees of severity ranging from ambulatory patients to wheelchair
bound patients. We examined the patients neurologically and by conducting
pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1
second, and static maximal inspiratory and expiratory mouth pressures. We did not
find pulmonary function test abnormalities in ambulant facioscapulohumeral
muscular dystrophy patients. Even though none of the patients complained of
respiratory dysfunction, mild to severe respiratory insufficiency was found in
more than one third of the wheelchair-dependent patients. Maximal inspiratory
pressures and maximal expiratory pressures were decreased in most patients, with
a trend that maximal expiratory pressures were more affected than maximal
inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis
showed the most restricted lung function. Wheelchair-dependent patients with
(kypho-)scoliosis are at risk for developing respiratory function impairment. We
advise examining this group of facioscapulohumeral muscular dystrophy patients
periodically, even in the absence of symptoms of respiratory insufficiency, given
its frequency and impact on daily life and the therapeutic consequences.
PMID- 28416349
TI - Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of
typical nemaline rods.
AB - Mutations in ACTA1 cause a group of myopathies with expanding clinical and
histopathological heterogeneity. We describe three patients with severe ACTA1
related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline
rods. Patient 1 is a five-year-old boy who presented at birth with severe
weakness and respiratory failure, requiring mechanical ventilation. Whole exome
sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation.
Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory
insufficiency at birth requiring mechanical ventilation. Both died at 6 months of
age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by
whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy
can present with muscle morphological findings suggestive of cytoplasmic body
myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in
skeletal muscle sarcomeric alpha-actin may be linked to this histological
appearance. These novel ACTA1 cases also illustrate the successful application of
whole exome sequencing in directly arriving at a candidate genetic diagnosis in
patients with unexpected phenotypic and histologic features for a known
neuromuscular gene.
PMID- 28416351
TI - Intraductal Carcinoma of the Prostate: Anonymous to Ominous.
PMID- 28416350
TI - Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial
Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy.
AB - BACKGROUND: There is increasing low-quality evidence rationalizing the use of
radical therapy for men at high risk of disseminated prostate cancer. OBJECTIVE:
To investigate, using high-quality epidemiologic data, whether initial radical
therapy in men at high risk of disseminated prostate cancer improves survival.
DESIGN, SETTING, AND PARTICIPANTS: An observational population-based Swedish
study from 1996 to 2010 of men at high risk of disseminated prostate cancer
(prostate-specific antigen [PSA] >50) initially treated by radical therapy
(radiation therapy [n=630] or radical prostatectomy [n=120]) or androgen
deprivation therapy (n=17 602), and followed for up to 15 yr. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-cancer and other-cause mortality
was estimated for the treatment groups. We also matched the two cohorts for
grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and
found androgen deprivation therapy patient matches for 575 of the radical therapy
patients, and then repeated comparative effectiveness analyses. RESULTS AND
LIMITATION: Prostate-cancer mortality was substantially greater in the androgen
deprivation therapy group compared with the radically treated one, in unmatched
(9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched
cohorts, initial androgen deprivation therapy was associated with nearly three
fold higher hazard of prostate-cancer death compared with initial radical therapy
(2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses
suggested that the findings were robust, although the general limitations of
nonrandomized studies remain. Further, the study cohort may have included men
with both systemic and nonsystemic disease, as a sole eligibility criterion of
PSA >50 was used. CONCLUSIONS: This large and comprehensive population-based
study suggests that initial radical therapy in men at high risk of disseminated
prostate cancer improves survival. PATIENT SUMMARY: This large Swedish study
suggests that men with prostate cancer that has spread beyond the prostate
benefit from treating the prostate itself with radiation therapy or surgery
rather than treating the disease with hormones alone.
PMID- 28416352
TI - Setting them up for lifetime activity: Play competence perceptions and physical
activity in young children.
AB - OBJECTIVES: Possessing positive physical perceived competence is important for
physical activity in older children. Young children are primarily physically
active through play-based behaviour rather than through organised sports and
activities, so understanding how play perceptions might influence physical
activity behaviour is important. The study purpose was to assess if perceived
active play competence is associated with young children's physical activity.
DESIGN: Cross sectional study. METHODS: This paper uses two different samples
drawn from the same Australian city, both collected in 2013. The first sample
included 152 children (49% boys) aged 4-5 years (M=4.7, SD=0.47), the second
sample included 78 children (55% boys) aged 5-8 years (M=6.6, SD=0.93). The
Pictorial Scale of Perceived Movement Skill Competence was used to assess
children's perceived competence in six skill-related play activities. Moderate-
to vigorous-intensity physical activity (MVPA) was assessed for 8 consecutive
days via accelerometers. A general linear model with the mean minutes in MVPA per
day as the outcome, perceived play competence as the independent variable and
adjusting for relevant confounders was performed in each sample. RESULTS:
Perceived active play competence was not related to MVPA min/day (B=0.44,
p=0.323) in the younger sample, but was in the older sample (B=1.53, p=0.026),
explaining 24% of adjusted variance. CONCLUSIONS: Positive findings in the older
sample show school-aged children need exposure to play based activities in order
to develop the positive self-perception needed to engage in MVPA every day.
PMID- 28416353
TI - Eating disorders and weight control behaviors change over a collegiate sport
season.
AB - OBJECTIVES: Determine whether the prevalence of eating disorder classifications
(i.e., clinical eating disorder, subclinical eating disorder, and asymptomatic)
and pathogenic weight control behaviors (e.g., bingeing, vomiting) change over a
five-month sport season. DESIGN: Longitudinal study. METHODS: Female collegiate
gymnasts and swimmers (N=325) completed the Questionnaire for Eating Disorder
Diagnoses as well as six items from the Bulimia Test-Revised at Time 1 (two weeks
into the beginning of their athletic season) and Time 2 (final two weeks of the
athletic season); data collections were separated by five months. RESULTS: Over
the course of the season, 90% of the athletes (18 out of 20) retained a clinical
eating disorder diagnosis or moved to the subclinical classification. Of the 83
subclinical athletes at Time 1, 37.3% persisted with that classification and
10.8% developed a clinical eating disorder; the remainder became
asymptomatic/healthy eaters by Time 2. The majority of Time 1 asymptomatic
athletes (92.3%) remained so at Time 2. Exercise and dieting/fasting were the
most frequent forms of weight control behaviors, though each was used less
frequently at Time 2 (exercise=35.4%; dieting=9.2%) than at Time 1
(exercise=42.5%; dieting=12.3%). CONCLUSIONS: Eating disorder classifications,
particularly clinical and subclinical, remain stable across a competitive season,
supporting the need for early detection and purposeful intervention. Athletes
engage in weight control behaviors that may be reinforced in the sport
environment (e.g., supplemental exercise), making identification more challenging
for sports medicine professionals.
PMID- 28416354
TI - Unilateral jumps in different directions: a novel assessment of soccer-associated
power?
AB - OBJECTIVES: We aimed to determine whether countermovement jumps (CMJs; unilateral
and bilateral) performed in different directions assessed independent lower-limb
power qualities, and if unilateral CMJs would better differentiate between elite
and non-elite soccer players than the bilateral vertical (BV) CMJ. DESIGN: Elite
(n=23; age, 18.1+/-1.0years) and non-elite (n=20; age, 22.3+/-2.7years) soccer
players performed three BV, unilateral vertical (UV), unilateral horizontal
forward (UH) and unilateral medial (UM) CMJs. METHODS: Jump performance (height
and projectile range), kinetic and kinematic variables from ground reaction
forces, and peak activation levels of the vastus lateralis and biceps femoris
(BF) muscles from surface electromyography, were compared between jumps and
groups of players. RESULTS: Peak vertical power (V-power) was greater in BV
(220.2+/-30.1W/kg) compared to UV (144.1+/-16.2W/kg), which was greater than UH
(86.7+/-18.3W/kg) and UM (85.5+/-13.5W/kg) (all, p<0.05) but there was no
difference between UH and UM (p=1.000). Peak BF EMG was greater in UH compared to
all other CMJs (p<=0.001). V-power was greater in elite than non-elite for all
CMJs (p<=0.032) except for BV (p=0.197). Elite achieved greater UH projectile
range than non-elite (51.6+/-15.4 vs. 40.4+/-10.4cm, p=0.009). CONCLUSIONS: We
have shown that UH, UV and UM CMJs assess distinct lower-limb muscular power
capabilities in soccer players. Furthermore, as elite players outperformed non
elite players during unilateral but not BV CMJs, unilateral CMJs in different
directions should be included in soccer-specific muscular power assessment and
talent identification protocols, rather than the BV CMJ.
PMID- 28416355
TI - Expression of coproporphyrinogen oxidase is associated with detection of upper
gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic
diagnosis.
AB - BACKGROUND: 5-Aminolevulinic acid is a precursor of photosensitizing
protoporphyrin IX and has been applied for photodynamic diagnosis of brain and
bladder tumors with few side effects. Although most upper gastrointestinal tumors
can be detected during photodynamic diagnosis, some tumors containing signet-ring
cells cannot be visualized. Here, we aimed to assess whether proteins involved in
the absorbance, activation, and turnover of protoporphyrin IX altered the
fluorescence signal in gastric cancer. METHODS: Aminolevulinic acid-mediated
photodynamic diagnosis was performed in 23 lesions from 20 patients using an
endoscope equipped with a blue laser light that caused red fluorescence emission
of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was
assessed during photodynamic diagnosis procedures. Lesions were resected by
endoscopic and/or laparoscopic surgery, and specimens were immunostained and
assessed for the expression of ATP-binding cassette sub-family G member 2,
oligopeptide transporter-1, and coproporphyrinogen oxidase. RESULTS: Photodynamic
diagnosis was negative in four cases (17.4%). Three cases of photodynamic
diagnosis-negative lesions were signet-ring cell carcinomas, and only one case
was differentiated adenocarcinoma (intestinal type). Twenty intestinal type,
photodynamic diagnosis-positive lesions showed high expression of
coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all
negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in
tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression
tended to be higher in luminal surface tumors than in intestinal type tumors.
CONCLUSION: Aminolevulinic acid-mediated photodynamic diagnosis provided good
detection of upper gastrointestinal tumors of intestinal type but not diffuse
type tumors, such as signet-ring cell carcinomas, possibly owing to
coproporphyrinogen oxidase expression.
PMID- 28416356
TI - Risk factors for free flap failure: a retrospective analysis of 881 free flaps
for head and neck defect reconstruction.
AB - The aim of this study was to identify the risk factors for free flap failure
after head and neck reconstructive surgery. The data of 881 consecutive patients
who underwent free flap surgery at the Department of Oral and Maxillofacial
Surgery, Peking University School and Hospital of Stomatology, between January
2013 and November 2016, were reviewed retrospectively. All surgeries were
performed by a single head and neck surgical team. Patient demographic and
surgical data that may have an influence on free flap outcomes were recorded. The
chi2 test and multivariate logistic regression analysis were used to identify
relevant risk factors. In total, 881 free tissue transfer surgeries were included
in this study. Free flap failure occurred in 26 of 881 flaps (2.9%). A history of
irradiation (odds ratio 0.205, 95% confidence interval 0.07-0.56; P=0.002) was a
statistically significant risk factor for free flap failure. Age, diabetes
mellitus, history of previous neck surgery to the anastomosis side, donor site,
choice of recipient vein, use of a coupler device, and postoperative
anticoagulation were not associated with free flap outcomes. Thus, it is
concluded that when performing head and neck reconstructive surgery, special
attention should be paid to patients who have previously undergone irradiation.
PMID- 28416357
TI - Complicated diverticular disease: Position statement on outpatient management,
Hartmann's procedure, laparoscopic peritoneal lavage and laparoscopic approach.
Consensus document of the Spanish Association of Coloproctology and the
Coloproctology Section of the Spanish Association of Surgeons.
AB - The Spanish Association of Coloproctology (AECP) and the Coloproctology Section
of the Spanish Association of Surgeons (AEC), propose this consensus document
about complicated diverticular disease that could be used for decision-making.
Outpatient management, Hartmann's procedure, laparoscopic peritoneal lavage, and
the role of a laparoscopic approach in colonic resection are exposed.
PMID- 28416358
TI - Non-gated high-pitch computed tomography aortic angiography: Myocardial perfusion
defects in patients with suspected aortic dissection.
AB - OBJECTIVES: To investigate the diagnostic value of first-pass myocardial
perfusion defects visualised in non-gated high-pitch computed tomography
angiography (CTA) in patients admitted to the emergency department (ED) for
suspected aortic dissection. METHODS: We recruited 174 ED patients who underwent
high-pitch CTA of the aorta because of suspected aortic dissection. We divided
these patients into two groups (diseased and control groups) based on whether
their clinical data fulfilled the third universal definition of acute myocardial
infarction (AMI), specifically an increase in cardiac troponin (cTn) with at
least one of the following: (a) symptoms of ischemia; (b) new ST-segment-T wave
(ST-T) changes or new left bundle branch block (LBBB); (c) development of
pathological Q wave; (d) new loss of viable myocardium or new regional wall
motion abnormality; or (e) identification of an intracoronary thrombus by
angiography or autopsy. Twenty-two patients with a clinical diagnosis of AMI were
placed in the diseased group. Myocardial perfusion defects were evaluated
qualitatively and quantitatively on the late arterial phase obtained 50 s post
threshold. RESULTS: Of the 22 patients with a final diagnosis of AMI, visually
identifiable perfusion defects were observed in 12 patients. The sensitivity,
specificity, negative predictive value, and positive predictive value of any
perfusion defect for predicting AMI were 54.6%, 94.7%, 93.5%, and 60.0%,
respectively. Quantitative analysis indicated that CT attenuation was
significantly lower within perfusion defects than within the normal myocardium
(67.6 +/- 29.5 HU vs. 92.2 +/- 19.7 HU; p < 0.001). CONCLUSIONS: In patients with
acute chest pain, the presence of myocardial perfusion defect observed on
nongated high-pitch CTA of the aorta can be used to identify individuals with AMI
with high specificity, but low sensitivity.
PMID- 28416359
TI - Marital status is an independent prognostic factor for pancreatic neuroendocrine
tumors patients: An analysis of the Surveillance, Epidemiology, and End Results
(SEER) database.
AB - BACKGROUND AND OBJECTIVES: Marital status's prognostic impact on pancreatic
neuroendocrine tumors (PNET) has not been rigorously studied. We aimed to explore
the relationship between marital status and outcomes of PNET. METHODS: We
retrospectively investigated 2060 PNET cases between 2004 and 2010 from
Surveillance, Epidemiology, and End Results (SEER) database. Variables were
compared by Chi2 test, t-test as appropriate. Kaplan-Meier methods and COX
proportional hazard models were used to ascertain independent prognostic factors.
RESULTS: Married patients had better 5-year overall survival (OS) (53.37% vs.
42.27%, P<0.001) and 5-year pancreatic neuroendocrine tumor specific survival
(PNSS) (67.76% vs. 59.82%, P=0.001) comparing with unmarried patients.
Multivariate analysis revealed marital status is an independent prognostic
factor, with married patients showing better OS (HR=0.74; 95% CI: 0.65-0.84;
P<0.001) and PNSS (HR=0.78; 95% CI: 0.66-0.92; P=0.004). Subgroup analysis
suggested marital status plays a more important role in the PNET patients with
distant stage rather than regional or localized disease. CONCLUSIONS: Marital
status is an independent prognostic factor for survival in PNET patients. Poor
prognosis in unmarried patients may be associated with a delayed diagnosis with
advanced tumor stage, psychosocial and socioeconomic factors. Further studies are
needed.
PMID- 28416360
TI - Primary hepatic angiosarcoma and liver transplantation: Radiological, surgical,
histological findings and clinical outcome.
AB - Angiosarcoma is a rare type of soft tissue sarcoma that accounts for less than 1%
of all sarcomas and only 2% of all primary hepatic tumours. Thorotrast, arsenic,
and vinyl chloride monomer are frequently listed as occupational exposure risks.
The estimated latency is long (10-40 years) in occupational cases and very long
(60 years or more) in non-occupational cases. The symptoms and CT-scan appearance
of hepatic angiosarcoma (HAS) are non-specific. We present a case of a 65-year
old Caucasian male with history of cryptogenic cirrhosis, low alpha-foetoprotein
levels and a single, 4-cm nodule of potential atypical hepatocellular carcinoma
(no washout at MRI and CT-scan) in segment VIII. Laparoscopic radiofrequency
ablation (a biopsy of the neoplastic lesion was technically impossible) was
performed, followed by liver transplantation (LT) 6 months later. High-grade
multifocal HAS was found in the explanted liver, with extensive involvement of
the venous portal structures. No complications were observed during the
postoperative course, and initial immunosuppression included tacrolimus,
mycophenolate mofetil and corticosteroids. Because of the histological findings,
tacrolimus was switched to everolimus as the main immunosuppressive drug one
month after LT. Despite this conversion, the patient developed bone metastases 3
months after LT and peritoneal carcinosis one month later. This case report
suggests that everolimus conversion does not inhibit the development of tumour
metastases. Consequently, HAS remains an absolute contraindication to LT because
of the poor outcome. If LT has been performed for incidental HAS, new molecular
therapies (e.g. vascular endothelial growth factor antagonists) should be
considered immediately after LT to improve the outcome.
PMID- 28416362
TI - In situ targeted activation of an anticancer agent using ultrasound-triggered
release of composite droplets.
AB - The efficiency of a drug is usually highly dependent on the way it is
administered or delivered. As such, targeted-therapy, which requires conceiving
drug-delivery vehicles that will change their state from a relatively stable
structure with a very slow leak-rate to an unstable structure with a fast
release, clearly improves the pharmacokinetics, the absorption, the distribution,
the metabolism and the therapeutic index of a given drug. In this context, we
have developed a particularly effective double stimuli-responsive drug-delivery
method allowing an ultrasound-induced release of a monomethylauristatin E
glucuronide prodrug and its subsequent activation by a beta-glucuronidase. This
led to an increase of cytotoxicity of about 80% on cancer cells.
PMID- 28416361
TI - Unraveling the Regulation of Hepatic Metabolism by Insulin.
AB - During insulin-resistant states such as type 2 diabetes mellitus (T2DM), insulin
fails to suppress hepatic glucose production but promotes lipid synthesis leading
to hyperglycemia and hypertriglyceridemia. Defining the downstream signaling
pathways underlying the control of hepatic metabolism by insulin is necessary for
understanding both normal physiology and the pathogenesis of metabolic disease.
We summarize recent literature highlighting the importance of both hepatic and
extrahepatic mechanisms in insulin regulation of liver glucose and lipid
metabolism. We posit that a failure of insulin to inappropriately regulate liver
metabolism during T2DM is not exclusively from an inherent defect in canonical
liver insulin signaling but is instead due to a combination of hyperinsulinemia,
altered substrate supply, and the input of several extrahepatic signals.
PMID- 28416363
TI - [Adequacy of treatment for osteoporosis in primary prevention. Quantitative and
qualitative study].
AB - OBJECTIVE: Quantitative study: To assess the prevalence of inadequacy of
treatment for osteoporosis in primary prevention (OPP) in women aged 60-74years.
Qualitative study: To evaluate the diagnostic and treatment criteria of the OPP
and it's variability in primary care physicians (PC) and specialists. MATERIAL
AND METHODS: Quantitative study: observational, cross-sectional and retrospective
study. POPULATION: women aged 60-74years with active treatment for OPP (n=424) in
May 2012. Inadequacy if they had <=2 risk factors with a DXA or DXA T-score >=
2.4. Qualitative study: Delphi technique (15items) and two rounds of
consultation. PERIOD: March-April 2014. POPULATION: PC physicians,
rheumatologists and orthopaedic surgeons (n=251). Random sampling. RESULTS:
Quantitative study: degree of inadequacy is 63.4%. In 43.2% isn't mention a
diagnosis of osteoporosis. In 82.3% there isn't mention of risk factors.
TREATMENT: bisphosphonate 40.3% and calcium +vitaminD 47.9%. Qualitative study:
23% respond to the first round, and of these 67% the second round. Items with
higher agreement were the important of the evaluation of risk factors for
diagnosis and bisphosphonates for treatment. Items with fewer consensuses were
using the FRAX and densitometry and treatment with only calcium +vitaminD.
CONCLUSIONS: The percentage of inadequacy is high. The degree of registration in
medical history is low. The Delphi method is useful for detecting discrepancies
between recommendations of clinical practice guidelines and results.
PMID- 28416364
TI - [Implementation of nurse demand managment in primary health care service
providers in Catalonia].
AB - OBJECTIVE: To describe and analyse the implementaction of nurse demand managment
(NDM) among health care providers in Catalonia from 2005 to 2014. DESIGN: Cross
sectional survey. Participants All service providers in Catalonia (n=37). Main
measurements Interviews with nurse manager of each health care provides about ht
barriers and facilitators concerning NDM. Facilitators and barriers were
classified into 3 types: (i)health professional (competence, attitudes,
motivation for change and individual characteristics); (ii)social context
(patients and companions), and (iii)system related factors (organization and
structure, economic incentives). RESULTS: Of the 37 providers, 26 (70.3%) have
implemented the Demand Management Nurse (NDM). The main barriers identified are
the nurse prescriptin regulation, lack of knowledge and skills of nurses, and the
lack of protocols at the start of implantation. Among the facilitators are the
specific training of professionals, a higher ratio of nurses to doctors,
consensus circuits with all professionals and linking the implementation of NDM
to economic incentives. DISCUSSION: NDM is consolidated in Catalonia. However,
the NDM should be included in the curricula of nursing degree and continuing
education programs in primary care teams.
PMID- 28416365
TI - [Increase in the number of diagnosed cases of whooping cough; Do we think more in
it?]
PMID- 28416366
TI - 2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase
4 inhibitor for atopic dermatitis.
AB - BACKGROUND: Crisaborole is a novel, topical nonsteroidal, anti-inflammatory,
phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild to moderate atopic
dermatitis. OBJECTIVE: As part of a nonclinical safety testing program, these 2
year studies tested the carcinogenic potential of crisaborole. METHODS:
Crisaborole ointment, 2%, 5%, or 7%, was applied once daily topically to mice,
and crisaborole was administered orally to rats at doses of 30, 100, or
300mg/kg/day for up to 104 weeks. Systemic exposure to crisaborole and its
metabolites, moribundity/death, clinical signs, and tumor formation were assessed
in each study. RESULTS: Crisaborole treatment was not tumorigenic in mice at any
of the doses administered and did not increase the incidence of neoplastic or
nonneoplastic microscopic lesions compared with controls. Oral administration of
crisaborole at the high dose (300mg/kg/day) to female rats increased the
incidence of treatment-related benign granular cell tumors in the distal
reproductive tract (uterus with cervix and vagina) but did not cause
moribundity/death. CONCLUSION: Crisaborole was well tolerated and not tumorigenic
in mice. It was not tumorigenic in male rats at 300mg/kg/day at exposures that
were 3* the human area under the concentration-time curve (AUC24) and was
nontumorigenic in female rats at 100mg/kg/day at exposures that were 1* the human
AUC24.
PMID- 28416367
TI - Serum Galanin Concentration is Increased in Subjects with Impaired Glucose
Tolerance.
AB - OBJECTIVES: Although extensive data have shown that galanin can regulate the food
intake and glucose metabolism of animals, little is known regarding the galanin
concentration in patients with impaired glucose tolerance (IGT). Therefore, the
aims of this study were to investigate whether serum galanin levels and other
metabolic parameters are changed in patients with IGT compared with controls with
normal glucose tolerance (NGT). METHODS: Data regarding serum galanin levels and
relative metabolic parameters were collected in 12 patients with IGT and 12
healthy patients with NGT. RESULTS: At 1 hour and 2 hours after dinner, serum
galanin, insulin and glucose levels were significantly higher in patients with
IGT than in controls with NGT. Additionally, the body weights of patients with
IGT was higher than those of the controls. Furthermore, a negative correlation
was found between galanin levels and 1-hour glucose concentrations (r=-0.580;
p=0.048) in patients with IGT. CONCLUSIONS: The higher serum galanin levels as
well as the negative correlation between galanin levels and 1-hour glucose
content in patients with IGT may result from the interaction between insulin and
galanin in differing conditions, suggesting that the galanin level may be used as
a potential biomarker for the prediction of IGT in clinical settings.
PMID- 28416368
TI - Nutritional management in women with polycystic ovary syndrome: A review study.
AB - Polycystic ovary syndrome (PCOS) is endocrine disorder in women of reproductive
age, which leads to reproductive, hormonal and metabolic abnormalities. Due to
the presence of insulin resistance, PCOS increases the risk of chronic diseases
like type 2 diabetes, hypertension, lipid disorders, cardiovascular diseases and
malignancies such as breast and endometrial cancer. The actual cause of this
syndrome is unknown but environmental factors such as dietary habits play an
important role in prevention and treatment and lifestyle modifications are the
most important therapeutic strategies in these patients. The approach of the diet
therapy in these patients must be to reach specific goals such as improving
insulin resistance, metabolic and reproductive functions that will be possible
through the design of low-calorie diet to achieve weight loss or maintaining a
healthy weight, limit the intake of simple sugars and refined carbohydrates and
intake foods with a low glycemic index, reduction of saturated and trans fatty
acids and attention to possible deficiencies such as vitamin D, chromium and
omega-3. Given the prevalence of overweight and obesity and insulin resistance, a
relatively low reduction in weight, about 5%, can improve problems such as
insulin resistance, high levels of androgens, reproductive system dysfunctions
and fertility in these women.
PMID- 28416370
TI - Editorial overview: Genome studies and molecular genetics.
PMID- 28416369
TI - Plasma levels of Apolipoprotein A1 and Lecithin:Cholesterol Acyltransferase in
type 2 diabetes mellitus: Correlations with haptoglobin phenotypes.
AB - BACKGROUND: Previous studies have demonstrated that hemoglobin-haptoglobin (Hb
Hp) complex plays a role in developing vascular complications in type 2 diabetes
mellitus (T2DM). The complexes bind with Apolipoprotein A1 (ApoA1) of high
density lipoprotein (HDL), affecting the function of Lecithin:Cholesterol
Acyltransferase (LCAT), and impairing the reverse cholesterol transport mechanism
(RCT). This study investigated the influence of Hp phenotypes on serum levels of
ApoA1 and LCAT in patients with T2DM. METHODS: The study comprised 131 T2DM
patients and 111 matching healthy controls. Fasting blood glucose, HbA1C, and
lipid profile were determined by chemistry autoanalyzer, LCAT and ApoA1 by ELISA,
and Hp phenotypes by gel electrophoresis. RESULTS: Irrespective of Hp phenotypes,
fasting blood glucose, HbA1C, and lipid profile were significantly higher in
patients than in controls, while HDL-cholesterol, ApoA1, and LCAT were lower.
ApoA1 correlated positively with LCAT (r=0.223, p=0.024) and HDL-cholesterol
(r=0.255, 0.003) in patients only. When Hp polymorphism was taken into account,
the levels of LCAT and ApoA1 were significantly lower in patients with Hp2-2 than
that in patients of Hp1-1 and/or Hp2-1. Correlations between ApoA1 and each of
HDL-cholesterol and LCAT (r=0.239, p=0.046, and r=0.252, p=0.040, respectively)
were also observed, but only in patients with Hp2-2 phenotype. CONCLUSIONS: The
reduced levels of LCAT and ApoA1 observed in this study support the suggestion
that T2DM patients with Hp2-2 phenotype could have altered RCT mechanism and
increased risk of developing cardiovascular disease.
PMID- 28416371
TI - Modulation by NADPH oxidase of the chronic cardiovascular and autonomic
interaction between cyclosporine and NSAIDs in female rats.
AB - Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used
together to manage arthritic disorders with an immune component. Previous reports
showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations
in blood pressure. Both effects were ameliorated or exaggerated after selective
cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we
investigated: (i) the interaction of CSA with NSAIDs possessing variable
COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac
autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho
kinase (ROCK) pathway in the interaction. Female rats were pre-instrumented with
femoral catheters and treated for 10 days with CSA (25mg/kg/day), diclofenac
(nonselective NSAIDs, 1mg/kg/day), celecoxib (COX2 inhibitor, 10mg/kg/day), or
their combinations. CSA-mediated hypertension was maintained upon co
administration of either NSAID whereas the concomitant reductions in time- and
frequency-domain indices of heart rate variability (HRV) were accentuated in
presence of diclofenac but not celecoxib. The isovolumic relaxation time (Tauau),
a measure of diastolic function, was reduced by all regimens whereas LV
contractility (dP/dtmax) remained unaffected. The CSA/diclofenac regimen, but not
individual treatments, increased cardiac NOX2 expression and caused more cardiac
structural damage. The inhibition of NOX by diphenyleneiodonium reversed
CSA/diclofenac-evoked increases in MAP, decreases in HRV and Tau, cardiac
structural damage, and increased NOX2 expression. No such effects were observed
after ROCK inhibition by fasudil, despite concomitant decreases in NOX2
expression. In conclusion, CSA/diclofenac-treated female rats exhibit exacerbated
hemodynamic, autonomic, LV, and histopathologic disturbances via ROCK-independent
NOX2 upregulation.
PMID- 28416372
TI - Effects of bilobalide, ginkgolide B and picrotoxinin on GABAA receptor modulation
by structurally diverse positive modulators.
AB - Anxiolytics and anticonvulsants generally positively modulate the action of GABA,
whereas many convulsants (including the chloride channel blocker picrotoxinin)
negatively modulate the action of GABA on GABAA receptors. Like picrotoxinin,
bilobalide and ginkgolide B, active constituents of Ginkgo biloba, have been
shown to negatively modulate the action of GABA at alpha1beta2gamma2L GABAA
receptors. However, unlike picrotoxinin, bilobalide and ginkgolide B are not
known to cause convulsions. We have assessed the action of bilobalide, ginkgolide
B and picrotoxinin on a range of GABAA modulators (etomidate, loreclezole,
propofol, thiopentone sodium, diazepam, and allopregnanolone), using two
electrode voltage clamp electrophysiology at recombinant alpha1beta2gamma2L GABAA
receptors expressed in Xenopus oocytes. The results indicate that bilobalide and
ginkgolide B differ from picrotoxinin in their ability to inhibit the actions of
a range of these structurally diverse GABAA positive modulators consistent with
these modulators acting on a multiplicity of active sites associated with GABAA
receptors. In the presence GABA, ginkgolide B was more potent than bilobalide in
inhibiting the GABA-potentiating effect of propofol, equipotent against
loreclezole and allopregnanolone, and less potent against etomidate, diazepam,
and thiopentone sodium. This indicates that in comparison to picrotoxinin,
bilobalide and ginkgolide B differ in their effects on the different modulators.
PMID- 28416373
TI - Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.
AB - This study aimed to evaluate the inhibitory effects and explore mechanisms of
chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH)
in mice. Benign prostatic hyperplasia model was induced in experimental groups by
daily subcutaneous injections of testosterone propionate (7.5mg/kg/d)
consecutively for 14 d. A total of 60 mice were randomly divided into six groups:
(Group 1) normal control group, (Group 2) benign prostatic hyperplasia model
control group, (Group 3) benign prostatic hyperplasia mice treated with
finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice
treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group
5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels
of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice
treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group).
Animals were sacrificed on the scheduled termination, pick out the eyeball to get
blood, then prostates were weighed and prostatic index were determined. Then the
serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeII5-alpha
reductase (SRD5A2) levels were measured and observed morphological changes of the
prostate. Comparing with benign prostatic hyperplasia model group, the high and
medium dose of chlorogenic acid could significantly reduce prostate index and
levels of acid phosphatase, prostatic acid phosphatase and typeII5-alpha
reductase (P<0.05 or P<0.01). These findings were supported by histopathological
observations of prostate tissues. Histopathological examination also indicated
that chlorogenic acid treatment at the high and medium doses inhibited
testosterone-induced prostatic hyperplasia. The results indicated that
chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia
model animals, and its mechanism might be related to inhibit typeII5-alpha
reductase activity.
PMID- 28416374
TI - Comparing Originator Biologics and Biosimilars: A Review of the Relevant Issues.
AB - PURPOSE: We provide a review of current knowledge on comparability between
biosimilars and originator biologics in view of the continuous evolution
occurring in this highly dynamic area. METHODS: English-language literature
indexed in MEDLINE was explored, without time limits, to July 31, 2016, using the
terms biosimilar, biotechnologic drug, biologic drug, monoclonal antibody, fusion
protein, and anti-tumor necrosis factor. The reference lists of identified
articles were examined carefully for additional pertinent publications. FINDINGS:
Biological medicines are much more structurally complex and extremely sensitive
to manufacturing conditions and therefore more difficult to characterize and
produce than small molecule drugs. Even minor changes in manufacturing may lead
to significant variations of the cellular systems used for biological production,
as well as to differences in the structure, stability, or other quality aspects
of the end product, all of which have the potential to affect tolerability and/or
efficacy and increase the risk of immune responses. Owing to these issues,
specific regulatory guidance on biosimilars is continuously evolving, and there
is some disagreement on which studies need to be implemented to approve a
biosimilar. According to current literature, the following points on biosimilars
deserve consideration: biosimilar development is characterized by global
harmonization, although several not fully answered questions remain regarding
extrapolation of indications, switching or interchangeability, and tolerability;
in patients with rheumatic diseases, the tolerability and efficacy of biosimilars
in clinical practice remain to be established; several medical and patient
associations have published position papers on biosimilars requesting that
safety, efficacy, and traceability be carefully considered; long-term
postmarketing studies should be implemented to allow physicians to gain
confidence in biosimilars. IMPLICATIONS: On the basis of current knowledge, and
taking into consideration both regulatory rules and medical society positions, it
can be concluded that, although cost savings are highly desirable, the approval
process for biosimilars needs to place tolerability and efficacy, supported by
scientifically sound evidence, as the highest priority. Moreover, physicians must
retain full authority regarding the decision about which biopharmaceutical to use
for treating patients.
PMID- 28416375
TI - Automatic and manual Doppler velocimetry measurements of the uterine artery in
pregnant ewes.
AB - We aimed to compare measurements of speed and blood flow parameters obtained
manually and automatically in the uterine arteries of pregnant ewes. Eighteen
Santa Ines ewes, confirmed to be pregnant, were followed every 2 weeks until
parturition. The systolic peak (PS), end diastolic velocity (ED), maximum and
average speed in the cardiac cycle (TAMAX and TAMEAN, respectively), pulsatility
index (PI), resistance index (RI) and the systole/diastole (S/D) ratio and body
flow volume (BFV) was measured. We began the wave evaluation automatically, then
the observer manually marked the beginning and end of the wave. To determine the
differences between manual and automatic methods, a t-test was used for each of
the study variables (PS, ED, TAMAX, TAMEAN, PI, RI, S/D, and BFV), with p<0.05
considered significant. Both methods were found to be effective for producing
estimates for the variables analyzed. With the exception of the IP, IR and S/D
(p<0.05), no significant differences were found between the methods. The manual
method underestimated the PI (1.00+/-0.21*1.04+/-0.20), S/D (2.51+/-0.43*2.40+/
0.44) and RI (0.57+/-0.07*0.59+/-0.07) compared with the automatic method
(p<0.05). The weakest correlations between methods were identified for the PI, RI
and S/D variables (p<0.001). Manual evaluation allowed more accurate
identification of the beginning and end of the systole and diastole, which may
influence the outcome of some variables.
PMID- 28416376
TI - Seminal plasma removal by density-gradient centrifugation is superior for goat
sperm preservation compared with classical sperm washing.
AB - Seminal plasma removal is routine in goat sperm cryopreservation protocols. The
classical washing procedure designed to accomplish this usually leaves the pellet
resulting from use of this procedure contaminated with dead sperm, debris, and
cells other than sperm. This contamination negatively affects viability of sperm
after cryopreservation. The present research was conducted to compare the effect
on chilled and frozen-thawed goat sperm of the classical washing method to that
of a selective washing method involving density gradient centrifugation (DGC). In
the first experiment, sperm variables were measured in freshly collected sperm,
and again after its washing with both methods and chilling at 5 degrees C for 0,
3, 24, 48, 72 or 96h. The DGC-washed sperm had greater (P<0.01) straight line
velocity (VSL), average path velocity (VAP) and progression ratio values at all
chilling times. The amplitude of lateral head displacement (ALH) was, however,
less (P<0.001) in the DGC-washed sperm at all chilling times. There was a
negative correlation (P<0.05) between ALH and VSL. In the second experiment
involving the freezing-thawing of sperm washed by using either method, aliquots
were post-wash diluted with a Tris-citric acid/glucose/egg yolk/glycerol-based
medium and frozen in liquid nitrogen for 5days. After thawing, neither the VCL,
VSL nor VAP of the DGC-washed samples were affected, whereas the traditionally
washed samples had less motility. In conclusion, the use of DGC was associated
with enhanced sperm motility variables after chilling and freezing-thawing. This
procedure would, therefore, be a useful means of removing seminal plasma from
goat semen and obtaining greater quality sperm for insemination purposes.
PMID- 28416377
TI - Comparison between two estradiol-progesterone based protocols for timed
artificial insemination in blocks in lactating Nelore cows.
AB - The aim of this study was to compare the use of artificial insemination in time
blocks (Artificial Insemination Blocks, AIB) using an 8 and 9 d estradiol
progesterone based protocol. In this experiment, lactating Nelore cows (n=253)
were subjected to two estradiol-progesterone based TAI protocols. On the morning
of Day 10 (8d group, n=124) or Day 11 (9d group, n=129), cows were examined by
ultrasonography to evaluate the diameter of the preovulatory follicle and were
inseminated once at one of the following time points, according to the diameter
of the pre-ovulatory follicle (POF): Block 0 (POF>=15mm, TAI 0h after
conventional TAI), Block 1 (POF 13.0-14.9mm, TAI 6h later), Block 2 (POF 10.1
12.9mm, TAI 24h later), and Block 3 (POF<=10.0mm, TAI 30h later). The pregnancy
per AI (P/AI) did not differ between 8d and 9d groups (P>0.05). Considering only
multiparous cows, however, P/AI tended to be greater in the 8d (64.1%) than in
the 9d group (49.3%; P=0.08). Cows from the 9d group tended to have a larger POF
than cows from the 8d group (P=0.07). In conclusion, these results provide
evidence that there is no difference between 8d or 9d protocols when using the
AIB technique. Use of the 8d estradiol-progesterone based protocol, however,
tended to increase pregnancy in multiparous cows.
PMID- 28416378
TI - Risks of contrast media applied via the gastrointestinal route.
PMID- 28416379
TI - Editorial: Feline behavior and cognition.
PMID- 28416380
TI - Spinal dopaminergic involvement in the antihyperalgesic effect of antidepressants
in a rat model of neuropathic pain.
AB - Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline
reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we
aimed to determine the involvement of the spinal dopaminergic system in the
antihyperalgesic effects of antidepressants in a rat model of neuropathic pain
induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague
Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia.
Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal
thresholds after intraperitoneal injection of amitriptyline, duloxetine,
milnacipran, and fluoxetine. D2-like receptors were blocked by intrathecal
administration of sulpiride. We also determined the concentrations of dopamine in
the spinal cord using microdialysis after injection of antidepressants. The
dopamine contents in the spinal dorsal horn were also measured in normal and SNL
rats at 2, 3, 4, and 8 weeks after SNL surgery. Intraperitoneal injection of
amitriptyline, duloxetine, milnacipran, and fluoxetine (3-30mg/kg) produced
antihyperalgesic effects, and prevented by intrathecal pre-injection of sulpiride
(30MUg). Microdialysis revealed the dopamine levels in the spinal cord were
increased after intraperitoneal injection of each antidepressant (10mg/kg).
Furthermore, the dopamine content in homogenized spinal cord tissue were
increased at 2 weeks after SNL and then subsequently declined. Our results
suggest that the effect of antidepressants against neuropathic pain is related to
modulation of not only noradrenalin and serotonin but also dopamine levels in the
spinal cord.
PMID- 28416381
TI - Potent bactericidal activity of silver nanoparticles synthesized from Cassia
fistula fruit.
AB - We demonstrated one-step synthesis of silver nanoparticles (AgNPs) from Cassia
fistula fruit extract and their antibacterial activity against E. coli and K.
pneumoniae. Biogenic AgNPs were characterized by scanning electron microscopy, X
Ray diffraction and fourier transform infrared spectroscopy. Results confirmed
spherical shaped AgNPs with an average crystallite size of ~69 nm. Dose-dependent
(0, 10, 20, 40 and 80 MUg mL-1) growth kinetic studies showed 100% potency
against E. coli (20 MUg mL-1) and K. pneumoniae (80 MUg mL-1) after 1 and 5 h,
respectively. Surface morphology analysis revealed formation of groove/pits in
the lysed cell membrane that eventually led to bacterial death.
PMID- 28416382
TI - Isolation, pathogenicity and characterization of a novel bacterial pathogen
Streptococcus uberis from diseased mandarin fish Siniperca chuatsi.
AB - In recent years, mandarin fish had a high mortality rate associated with abnormal
swimming, exophthalmia, corneal opacity and eye hemorrhage on a fish farm located
at Foshan city, Guangdong province, China. Three isolates of Gram-positive, chain
forming cocci were recovered from moribund fish, and designated as SS131025-1,
SS131025-2, and SS131025-3. These isolates were identified as Streptococcus
uberis according to their morphologic and physio-biochemical characteristics as
well as phylogenetic analysis based on their 16S rRNA and GapC gene sequences.
The pathogenicity of S. uberis to mandarin fish was determined by challenge
experiments. Results of artificial challenge showed S. uberis infected healthy
mandarin fish and lead to death by eyeball injection or immersion route, and the
LD50 of SS131025-1 with eyeball injection was 2.0 * 106.42 CFU per fish. Moreover
extracellular product (ECP) of the isolated S.uberis induced CPB cell apoptosis
and cause death of mandarin fish. In addition, these S. uberis strains could also
infect tilapia, but not grass carp and crucian carp, and grew in brain-heart
infusion broth with an optimal temperature of 37 degrees C, pH of 7.0, and
salinity of 0%. Antibiotic sensitivity testing indicated that these isolates were
susceptible to rifampicin and furazolidone but resistant to 20 kinds of
antibiotics. Histopathologically, infection with S. uberis could cause serious
pathological changes in brain tissues such as vacuoles in matrix, swollen
mitochondria with lysis of cristae and disintegration, and lots of coccus was
observed both under electron and light microscope. These results shed some light
on the pathogenicity of the isolates and how to prevent and control S. uberis
infection in mandarin fish.
PMID- 28416383
TI - Comparative characterization analysis of synonymous codon usage bias in classical
swine fever virus.
AB - Classical swine fever virus (CSFV) is responsible for the highly contagious viral
disease of swine, and causes great economic loss in the swine-raising industry.
Considering the significance of CSFV, a systemic analysis was performed to study
its codon usage patterns. In this study, using the complete genome sequences of
76 CSFV representing three genotypes, we firstly analyzed the relative nucleotide
composition, effective number of codon (ENC) and synonymous codon usage in CSFV
genomes. The results showed that CSFV is GC-moderate genome and the third-ended
codons are not preferentially used. Every ENC values in CSFV genomes are >50,
indicating that the codon usage bias is comparatively slight. Subsequently, we
performed the correspondence analysis (COA) to investigate synonymous codon usage
variation among all of the CSFV genomes. We found that codon usage bias in these
CSFV genomes is greatly influenced by G + C mutation, which suggests that
mutational pressure may be the main factor determining the codon usage biases.
Moreover, most of the codon usage bias among different CSFV ORFs is directly
related to the nucleotide composition. Other factors, such as hydrophobicity and
aromaticity, also influence the codon usage variation among CSFV genomes. Our
study represents the most comprehensive analysis of codon usage patterns in CSFV
genome and provides a basic understanding of the mechanisms for its codon usage
bias.
PMID- 28416384
TI - Overexpressed HSPA2 correlates with tumor angiogenesis and unfavorable prognosis
in pancreatic carcinoma.
AB - Heat shock-related 70-kDa protein 2 (HSPA2) is known to correlate with tumor
development and progression. This work aimed to determine the expression and
prognostic roles of HSPA2 in pancreatic carcinoma. Tumor and their corresponding
non-tumor tissues were obtained from 80 patients with pancreatic carcinoma. HSPA2
expression in tumor and non-tumor tissues was evaluated by immunohistochemistry.
Expression of vascular endothelial growth factor (VEGF) and CD31 in tumor tissues
were also evaluated by immunostaining. The relationships of HSPA2 with
clinicopathological data, tumor angiogenesis and prognosis were analyzed. The
results showed that HSPA2 expression was significantly elevated in tumor tissues
compared with adjacent non-tumor tissues (P < 0.05). High HSPA2 expression was
significantly associated with aggressive clinicopathological characteristics.
HSPA2 staining was positively correlated with VEGF (r = 0.466, P < 0.001) and
microvessel density (MVD) (r = 0.366, P = 0.001) in tumor tissues. Patients with
high HSPA2 expression showed worse relapse-free survival (RFS) (P < 0.001) and
overall survival (OS) (P < 0.001) than those with low HSPA2 expression.
Multivariate analysis indicated that high HSPA2 expression was an independent
predictor for poor RFS (P < 0.001) and OS (P = 0.001). Taken together,
overexpressed HSPA2 is correlated with tumor angiogenesis and poor prognosis in
pancreatic carcinoma. HSPA2 may play an important role in tumor progression, and
serve as a potential biomarker for the prediction of adverse prognosis in
pancreatic carcinoma.
PMID- 28416385
TI - Abdominal adiposity and low physical activity are independently and inversely
associated with bone mineral density.
AB - BACKGROUND AND METHODS: Obesity is a highly heterogeneous condition, and the link
between adiposity distribution profiles and skeletal health is not well
understood. This study examined the association between adiposity and bone
mineral density (BMD) in a large cohort (5268 individuals) of US adults aged 20
85 years. RESULTS: Body mass index (BMI) and moderate-to-vigorous physical
activity were positively associated with BMD. Conversely, abdominal adiposity was
negatively associated with BMD, even after adjusting for age, race, BMI, and
objectively-measured physical activity. CONCLUSIONS: These findings highlight the
negative influence of abdominal adiposity on BMD and contradict the notion that
excess fat mass is protective for bone health.
PMID- 28416386
TI - Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the
Mycobacterium tuberculosis repressor EthR2.
AB - Inhibition of transcriptional regulators of bacterial pathogens with the aim of
reprogramming their metabolism to modify their antibiotic susceptibility
constitutes a promising therapeutic strategy. One example is the bio-activation
of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by
inhibiting the transcriptional repressor EthR. Recently, we discovered that
inhibition of a second transcriptional repressor, EthR2, leads to the awakening
of a new ethionamide bio-activation pathway. The x-ray structure of EthR2 was
solved at 2.3 A resolution in complex with a compound called SMARt-420 (Small
Molecule Aborting Resistance). Detailed comparison and structural analysis
revealed interesting insights for the upcoming structure-based design of EthR2
inhibitors as an alternative to revert ethionamide resistance in Mycobacterium
tuberculosis.
PMID- 28416387
TI - Differential regulation of the lipoxygenase pathway in shrimp hepatopancreases
and ovaries during ovarian development in the black tiger shrimp Penaeus monodon.
AB - Dietary polyunsaturated fatty acids (PUFAs) are critical to the success of
ovarian development in marine crustaceans, especially for domesticated species
such as the black tiger shrimp Penaeus monodon. These fatty acids are stored in a
midgut gland called the hepatopancreas and subsequently serve as an energy source
or are incorporated in yolk during ovarian development. PUFAs are known
precursors of hydroxy fatty acids, including hydroxyeicosatetraenoic acid and
hydroxyeicosapentaenoic acid (HEPE), which are catalyzed by lipoxygenases (LOX).
In previous studies, 8-HEPE has been shown to regulate female reproduction and
adipogenesis in marine crustaceans. However, whether the biosynthesis of 8-HEPE
in these species is the result of LOX activity has yet to be investigated. In
this study, 8-HEPE was identified exclusively in P. monodon hepatopancreases
using liquid chromatography-mass spectrometry. Treatment with
nordihydroguaiaretic acid resulted in the reduction of 8-HEPE, suggesting the
enzyme-dependent catalysis of 8-HEPE in hepatopancreases. Additionally, a full
length P. monodon LOX (PmLOX) was amplified from shrimp ovary cDNA. Sequence
analysis revealed that the putative PmLOX contains domains and catalytic residues
required for LOX catalytic function. Furthermore, PmLOX expression increased
steadily as shrimp ovary maturation progressed, while PmLOX expression and the
amount of 8-HEPE decreased in shrimp hepatopancreases. These findings not only
suggest differential requirements for hydroxy fatty acid biosynthesis in shrimp
ovaries and hepatopancreases during the P. monodon ovarian development, but also
provide insights into the LOX pathway in marine crustaceans.
PMID- 28416388
TI - Human GRP78 affinity towards its signaling partners Ire1alpha and PERK is
differently modulated by an unfolded protein client.
AB - Protein-folding stress is characteristic of specialized secretory cells and plays
a dominant role in a multitude of diseases. The unfolded protein response (UPR)
thus triggered is a proteostatic signaling network that adapts the protein
folding capacity of the endoplasmic reticulum to the cellular demands. We have
measured the binding affinities between human GRP78, an essential chaperone
located in ER, and two transmembrane UPR sensors (human PERK and Ire1alpha), with
or without the addition of an unfolded protein client. We reveal distinct binding
affinities between the binary and ternary complexes thus formed, that suggest a
preference for the PERK signaling branch under stress, and a predilection for the
GRP78-UPR sensor complex formation upon stressor removal. These results imply a
gated UPR mechanism that tunes the overall cellular behavior to the accumulation
of unfolded proteins.
PMID- 28416390
TI - Fluoroscopy-guided placement of pull-type mushroom-retained gastrostomy tubes in
102 patients.
AB - PURPOSE: The purpose of this study was to evaluate the technical and clinical
results of fluoroscopy-guided placement of pull-type mushroom-retained
gastrostomy tubes. MATERIALS AND METHODS: This retrospective study included 102
patients (61 men, 41 women) with a mean age of 59years+/-16.3 (SD) (range, 18
94years) who had fluoroscopy-guided placement of pull-type mushroom-retained
gastrostomy tubes. All procedures were performed after inflating the stomach with
air via an orally inserted 5-Fr catheter by retrograde catheterization of the
esophagogastric junction. Demographic data, results of the procedures and
complications were evaluated. RESULTS: A technical success was observed in
101/102 patients, yielding a technical success rate of 99%. Complications due to
the procedure were observed in 17/102 patients yielding a procedure-related
complication rate of 16.7%. Procedure-related complications included peristomal
superficial cellulitis (6/102; 5.9%), peristomal abscess (4/102; 3.9%),
subcutaneous hematoma (3/102; 2.9%), peristomal leakage (2/102; 2%), inadvertent
removal of the tube (1/102; 1%) and death due to procedure-related peritonitis
(1/102; 1%). CONCLUSION: Fluoroscopy-guided placement of pull-type mushroom
retained gastrostomy tubes is a feasible and effective method for enteral
nutrition.
PMID- 28416389
TI - Shp1 positively regulates EGFR signaling by controlling EGFR protein expression
in mammary epithelial cells.
AB - SH2-domain containing protein tyrosine phosphatase 1 (Shp1/PTPN6) is mainly
expressed in hematopoietic cells and acts a negative signaling regulator.
Although Shp1 is also expressed in epithelial cells, the function of shp1 in
normal epithelial is still less well understood, especially in regulating the
growth of epithelial cells. In this study, different shRNAs and siRNAs against
Shp1 were used to knockdown Shp1 expression in MCF10A, an immortalized mammary
epithelial cell line. Shp1 knockdown resulted in inhibited cell growth in part
due to lower percentage of MCF10A cells entering into S phase and reduced cyclin
D1 expression. Accordingly, EGF-induced tyrosyl phosphorylation of EGFR and Stat5
was significantly inhibited in cells with Shp1 knockdown compared with control
whereas EGF-induced Akt and Erk phosphorylation was not affected by Shp1
knockdown. Further analysis revealed that Shp1 knockdown lead to decreased EGFR
protein expression without affecting EGFR mRNA expression or increasing EGFR
protein degradation. Our data indicate that Shp1 functions as a positive
regulator and acts in a novel mechanism through promoting EGFR protein expression
in mammary epithelial cells.
PMID- 28416391
TI - Ultrasound Guided Out-of-Plane Versus In-Plane Transpectoral Left Axillary Vein
Cannulation.
AB - OBJECTIVE: The primary objective was to compare the frequency of first-attempt
successful axillary vein cannulation by the Seldinger technique using out-of
plane ultrasound guidance versus in-plane imaging. Between the two ultrasound
imaging planes, this study also compared the number of attempts that were
necessary for the cannulation of the left axillary vein along with the number of
needle redirections that had to be done for final cannulation of the vein.
Incidence of complications and the number of times the procedure was abandoned
also were compared between the two imaging planes. DESIGN: Prospective,
randomized, interventional study. SETTING: Tertiary care cardiac center.
PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: Left axillary vein
cannulation under ultrasound guidance by Seldinger technique. MEASUREMENTS AND
MAIN RESULTS: The left axillary vein was accessed under ultrasound guidance in 86
consecutive adult cardiac surgical patients. They were randomized to out-of-plane
(Group I, n = 43) and in-plane (Group II, n = 43) groups. In group I, the number
of first-attempt cannulations was very high (p < 0.01). The number of attempts to
access the vein was significantly lower in this group (p < 0.05). The duration
for completion of the procedure was also less in group I with out-of-plane
ultrasound guidance (p < 0.01). The number of needle redirections and the
incidence of complications (arterial puncture, pneumothorax hematoma formation)
were similar between the groups. There was no difference in the number of times
the procedure was abandoned between the two groups. With an assumption that the
first 10 patients in each group would suffice for overcoming the learning curve,
the above aspects were analyzed further in each group. The first-attempt
cannulation success continued to be significantly higher in the out-of-plane
group. CONCLUSIONS: Out-of-plane ultrasound imaging during axillary vein
cannulation increased the chance of first-attempt successful cannulation.
Axillary vein cannulation under out-of-plane ultrasound imaging also appeared to
be quicker and was preferable in terms of the fewer number of attempts that were
necessary for a successful vein cannulation.
PMID- 28416392
TI - Right Ventricular Function After Cardiac Surgery Is a Strong Independent
Predictor for Long-Term Mortality.
AB - OBJECTIVE: To establish the all-cause mortality of right ventricular dysfunction
after cardiac surgery in a heterogeneous group of cardiac surgery patients.
DESIGN: Retrospective analysis of a heterogeneous group of 1,109 cardiac surgery
patients in a 4-year period. SETTING: Single-center study in a tertiary teaching
hospital. PARTICIPANTS: One thousand one hundred nine cardiac surgery patients.
By protocol, patients were monitored with a pulmonary artery catheter, enabling
continuous right ventricular ejection fraction (RVEF) measurements.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements were performed
once per minute for the first 24 postoperative hours and expressed as average
over the complete period. Primary outcome was 2-year all-cause mortality. RVEF
was categorized into 3 subgroups: <20%, 20-30%, and >30%. Median follow-up time
was 739 days. Two-year mortality was significantly different across groups: 4.1%
for patients with RVEF >30%, 8.2% in the group with RVEF 20-30%, and 16.7% for
patients with RVEF <20%, p < 0.001. Additional risk factors for a poor RVEF were
age, body weight, New York Heart Association class, chronic obstructive pulmonary
disease, poor left ventricular function, and higher risk scores (Acute Physiology
and Chronic Health Evaluation and European System for Cardiac Operative Risk
Evaluation). In a multivariate analysis, RVEF as a continuous variable was
associated independently with the primary outcome (odds ratio 0.95 confidence
interval 0.91-0.99, p = 0.011.) Odds ratios for RVEF <20% were 1.88 (confidence
interval 1.18-3.00, p = 0.008). CONCLUSIONS: Right ventricular function is
associated independently with 2-year all-cause mortality in a heterogenic cardiac
surgery population.
PMID- 28416394
TI - Moderate reagent mixing on an orbital shaker reduces the incubation time of
enzyme-linked immunosorbent assay.
AB - Rapid diagnostic tests can be developed using ELISA for detection of diseases in
emergency conditions. Conventional ELISA takes 1-2 days, making it unsuitable for
rapid diagnostics. Here, we report the effect of reagents mixing via shaking or
vortexing on the assay timing of ELISA. A 48-min protocol of ELISA involving 12
min incubations with reagent mixing at 750 rpm for every step was optimized.
Contrary to this, time-optimized control ELISA performed without mixing produced
similar results in 8 h, leaving a time gain of 7 h using the developed protocol.
Collectively, the findings suggest the development of ELISA-based rapid
diagnostics.
PMID- 28416393
TI - TDP-43 expression influences amyloidbeta plaque deposition and tau aggregation.
AB - Although the main focus in Alzheimer's disease (AD) has been an investigation of
mechanisms causing Abeta plaque deposition and tau tangle formation, recent
studies have shown that phosphorylated TDP-43 pathology is present in up to 50%
of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been
associated with more severe AD pathology. Therefore, we hypothesized that TDP-43
may regulate amyloid-beta precursor protein (APP) trafficking and tau
phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we
developed a transgenic mouse that overexpresses hippocampal and cortical neuronal
TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and
presenilin 1 (PSEN1DeltaE9). In our model, increased TDP-43 was related to
increased tau aggregation as evidenced by thioflavin S-positive phosphorylated
tau, which may implicate TDP-43 expression in pre-tangle formation. In addition,
there was increased endosomal/lysosomal localization of APP and reduced Abeta
plaque formation with increased TDP-43. Furthermore, there was decreased
calcineurin with elevated TDP-43 expression. Since calcineurin is a phosphatase
for TDP-43, the decreased calcineurin expression may be one mechanism leading to
an increase in accumulation of diffuse phosphorylated TDP-43 in the hippocampus
and cortex. We further show that when TDP-43 is knocked down there is an increase
in calcineurin. In our model of selective TDP-43 overexpression in an APP/PSEN1
background, we show that TDP-43 decreases Abeta plaque deposition while
increasing abnormal tau aggregation. These observations indicate that TDP-43 may
play a role in regulating APP trafficking and tau aggregation. Our data suggest
that TDP-43 could be a putative target for therapeutic intervention in AD
affecting both Abeta plaque formation and tauopathy.
PMID- 28416395
TI - The early history of manganese and the recognition of its neurotoxicity, 1837
1936.
AB - The history of the biomedical recognition manganese-caused neurotoxicity mirrors
changing technologies as much as it does the ontology of parkinsonism. The
initial 1837 report of manganese-induced neurologic injury was made by John
Couper, a university-based physician in Scotland. He made clear that the outbreak
occurred among workers at the Charles Tennant bleach manufactory in the environs
of Glasgow. The relatively new technology of chlorine generation using manganese
accounted for the novel exposure involved. At the time, this factory was the
largest hypochlorite bleaching powder producer in the world. As the 19th century
progressed, technological change in steel fabrication requiring higher manganese
content greatly increased demand for the metal. Nonetheless, more than six
decades elapsed before the next reports of manganese neurotoxicity emerged. Two
unrelated outbreaks (both on Continental Europe) were reported within weeks of
each other in 1901, one by von Jaksch and the other by Embden. All the cases were
heavily exposed to manganese-containing dust. By the eve of the First World War,
a total of 9 patients with manganese-caused neurologic illness had been reported
in five separate Continental European publications. Meanwhile, new technology led
to another exposure source. Magnetic separation techniques allowed the extraction
of zinc from mixed ore also containing iron and manganese, leading to
exploitation of a unique source of high manganese-content ore found in New
Jersey. Not long after that technology's introduction, in 1912 Casamajor reported
the first U.S. cases of manganism, detailing classic findings. Additional cases
from the same cohort were reported a few years later, with continued exposure
driven by First World War-driven demand for manganese to be used in armaments.
The nosology of chronic manganese neurotoxicity remained in flux, with
considerable emphasis on shared attributes with Wilson's disease, a syndrome only
then recently described. A landmark 1924 primate study by Mella showed manganese
induced basal ganglion damage; human autopsy study data in the years following
further supported the view that manganese toxicity represented a parkinsonian
syndrome. As the 1937 centenary of Couper's first report approached, newer
technologies (electric arc welding and battery making) were being linked to
manganese-caused disease, even as mineral extraction was expanding as a global
source of exposure.
PMID- 28416396
TI - Chitosan composite three dimensional macrospheric scaffolds for bone tissue
engineering.
AB - The present work deals with the fabrication of chitosan composite scaffolds with
controllable and predictable internal architecture for bone tissue engineering.
Chitosan (CS) based composites were developed by varying montmorillonite (MMT)
and hydroxyapatite (HA) combinations to fabricate macrospheric three dimensional
(3D) scaffolds by direct agglomeration of the sintered macrospheres. The
fabricated CS, CS/MMT, CS/HA and CS/MMT/HA 3D scaffolds were characterized for
their physicochemical, biological and mechanical properties. The XRD and ATR-FTIR
studies confirmed the presence of the individual constituents and the molecular
interaction between them, respectively. The reinforcement with HA and MMT showed
reduced swelling and degradation rate. It was found that in comparison to pure
CS, the CS/HA/MMT composites exhibited improved hemocompatibility and protein
adsorption. The sintering of the macrospheres controlled the swelling ability of
the scaffolds which played an important role in maintaining the mechanical
strength of the 3D scaffolds. The CS/HA/MMT composite scaffold showed 14 folds
increase in the compressive strength when compared to pure CS scaffolds. The
fabricated scaffolds were also found to encourage the MG 63 cell proliferation.
Hence, from the above studies it can be concluded that the CS/HA/MMT composite 3D
macrospheric scaffolds have wider and more practical application in bone tissue
regeneration applications.
PMID- 28416397
TI - Monitoring thermal and chemical unfolding of Brugia malayi calreticulin using
fluorescence and Circular Dichroism spectroscopy.
AB - Calreticulin of Brugia malayi (BmCRT) play very important role in host-parasite
interaction. In previous study it was found that BmCRT is responsible for
prevention of host classical complement pathway activation via its interaction
with first component C1q of the human host. Therefore, BmCRT is an essential
protein for parasite survival and an important drug target to fend filariasis. In
the present study, we have carried out a systamatic biophysical characterization
of BmCRT protein. Unfolding of BmCRT was found to be non-cooperative two-state
process in the presence of both denaturant GdmCl and urea. The results also
illustrated that protein lost its 50% activity at 1.5M GdmCl and 3M Urea.
Partially unfolded and molten-globule like intermediate state was observed at 0.8
to 1.2M GdmCl while Urea unfolding showed intermediate state at 1.2 to 1.6M.
Unfolding pathway monitored with the help of apolar quencher, favor above
observations. All of these findings support the presence of detectable
intermediate state during unfolding pathway of BmCRT. Furthermore, this study
indicates that BmCRT is more stable toward temperature (Tm=65 degrees C), pH and
trypsin digestion. These differences in properties as compared to host can be
fruitfully utilized for synthesis of compounds effective against the parasite.
PMID- 28416398
TI - Synthesis, characterization, and evaluation of poly(aminoethyl) modified chitosan
and its hydrogel used as antibacterial wound dressing.
AB - This study aims to develop new antibacterial hydrogel wound dressings composed of
poly(aminoethyl) modified chitosan (PAEMCS). FTIR, 1H NMR, and elemental analysis
demonstrated that PAEMCS was successfully synthesized via grafting
poly(aminoethyl) groups onto hydroxyl groups on chitin first, and removing acetyl
groups from the grafted polymer afterward. XRD and TGA implied its well-defined
crystallinity and thermostability. Furthermore, a series of hydrogels were
fabricated under the participation of dipotassium hydrogen phosphate (DHP). The
gelation tests suggested that the higher concentration of PAEMCS or DHP was
beneficial to the formation of hydrogels. The pH values of hydrogels at 37
degrees C were all in the range of 7.12-7.50. The rheological tests indicated
that PAEMCS-based hydrogels were of lower DHP addition and higher elasticity than
CS-based hydrogels to achieve the same gelation temperature under the same
polymer's concentration. Additionally, the swelling, anti-bacteria, and
cytotoxicity experiments showed that PAEMCS-based hydrogels possessed excellent
hygroscopicity, high antibacterial activity against E. coli, S. aureus, or S.
epidermidis, and good cytocompatibility toward L929 cells or HUVECs,
respectively. All the results implied that PAEMCS-based hydrogels not only
maintained inherent multiple properties of chitosan but also possessed excellent
antibacterial activity, and might be promising antibacterial hydrogel dressings
used in wound therapy.
PMID- 28416399
TI - Fabrication of semisynthetic collagenic materials for mere/synergistic
adsorption: A model approach of determining dye allocation by systematic
characterization and optimization.
AB - Bovine collagen was functionalized by extensive process modifications for
fabricating tanned bovine collagen fibers (TBCFs), as a new semisynthetic macro-,
meso- and micro- porous adsorbent, of unprecedented physicochemical properties
and excellent industrial waste removal efficiency. Mere or interactive effects
were rationally understood, via analyzing monomer-dimer equilibrium, H-/J
aggregate formation, H-bonding, metachromasia, dye-dye complex formation etc.,
through extensive UV-vis analyses, during removal of acidic, like Acid Brown 369
(AB369), Acid Red 131 (AR131) and Acid Blue 113 (AB113) and basic, like Methylene
Blue (MB) dyes. A new strategy was introduced to determine the allocations of
these dyes, within macro-, meso- and micro-pores of TBCF, confirmed by FTIR, TGA,
DTG, DSC, XRD, SEM, EDX analyses, of both loaded and unloaded TBCFs, and by
measuring isotherm, kinetics, diffusion and thermodynamics parameters of
adsorption. Freundlich, Langmuir and Sips models were best fitted to AR131, AB113
and AB369, respectively. Interactive effects of concentration, temperature and
time, on adsorption capacities (ACs), were optimized via response surface
methodology (RSM). ACs of AR131, AB113 and AB369 were 38.29, 78.14 and 73.25mgg
1, respectively, at optimum conditions (i.e. adsorbent dose=0.25g, pHi=4,
concentration=200ppm and temperature=299K).
PMID- 28416400
TI - American Society for Metabolic and Bariatric Surgery: care pathway for
laparoscopic sleeve gastrectomy.
PMID- 28416401
TI - Polymeric nanoparticles for siRNA delivery: Production and applications.
AB - Gene therapy through the use of siRNA and a polymeric carrier are becoming an
efficient therapeutic option to conventional pharmaceutical formulations for the
treatment of deadly diseases, such as cancer, pulmonary, ocular and
neurodegenerative diseases. However, several considerations regarding the
stability, formulation, and efficacy have to be faced up until these systems
could be considered to be a marketable pharmaceutical products for to extend
siRNA application to clinical practice. This review is focused on the key
challenges of siRNA therapeutics, with special attention on the faced obstacles
and on the formulation-related difficulties, providing a list of requirements
needed for obtaining an ideal carrier for siRNA. Moreover, the current non-viral
polymers investigated for the realization of efficient carriers for siRNA are
described, with a special attention on synthetic polyamines such as
polyethylenimine (PEI), polysaccharides such as chitosan and inulin (INU), and
polyaminoacids such as alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA)
and poly-l-lysine (PLL).
PMID- 28416402
TI - Improvement of skin whitening agents efficiency through encapsulation: Current
state of knowledge.
AB - Hyperpigmentation is one of the most common skin disorder that affects both men
and women of all ethnic groups, caused by several factors, such as UV exposure
and skin inflammation. Topical whitening agents were found to be the best and the
least aggressive therapy for treating hyperpigmentation compared to instrumental
approaches. However, topical treatment faces several obstacles due to the low
stability of the whitening agents. Therefore, the encapsulation of these agents
was found to be crucial as it enhances their physicochemical stability and
increases their concentration at the targeted site via an improved skin
permeation, penetration or distribution. In this article, we review the
literature aimed to enhance the stability and the targeting of skin whitening
agents through their encapsulation in various nano and micro-particulate systems.
PMID- 28416403
TI - Feasibility of dsRNA treatment for post-clearing SPF shrimp stocks of newly
discovered viral infections using Laem Singh virus (LSNV) as a model.
AB - Using post-larvae derived from specific pathogen free (SPF) stocks in penaeid
shrimp farming has led to a dramatic increase in production. At the same time,
new pathogens of farmed shrimp are continually being discovered. Sometimes these
pathogens are carried by shrimp and other crustaceans as persistent infections
without gross signs of disease. Thus it is that a 5-generation stock of Penaeus
monodon SPF for several pathogens was found, post-stock-development, to be
persistently-infected with newly-discovered Laem Singh virus (LSNV). In this
situation, the stock developers were faced with destroying their existing stock
(developed over a long period at considerable cost) and starting the whole stock
development process anew in order to add LSNV to its SPF list. As an alternative,
it was hypothesized that injection of complementary dsRNA into viral-infected
broodstock prior to mating might inhibit replication of the target virus
sufficiently to reduce or eliminate its transmission to their offspring.
Subsequent selection of uninfected offspring would allow for post-clearing of
LSNV from the existing stock and for conversion of the stock to LSNV-free status.
Testing this hypothesis using the LSNV-infected stock described above, we found
that transmission was substantially reduced in several treated broodstock
compared to much higher transmission in buffer-injected broodstock. Based on
these results, the model is proposed for post-clearing of SPF stocks using dsRNA
treatment. The model may also be applicable to post-clearing of exceptional,
individual performers from grow-out ponds for return to a nucleus breeding
center.
PMID- 28416404
TI - Genomic and antigenic characterization of bovine parainfluenza-3 viruses in the
United States including modified live virus vaccine (MLV) strains and field
strains from cattle.
AB - This study investigated the genetic and antigenic characterization of
parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time
PCR and viral genome sequencing, PI3V strains could be separated into PI3V types,
including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine
respiratory disease clinical signs and commercial vaccines in the U.S. with MLV
PI3V were typed using these molecular tests. All the MLV vaccine strains tested
were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines
were types heterologous to the vaccine type A. Also antigenic differences were
noted as PI3V C strains had lower antibody levels than PI3V A in serums from
cattle receiving MLV PI3V A vaccines. This study further demonstrates there is
genetic variability of U.S. PI3V strains and also antigenic variability. In
addition, isolates from cattle with BRD signs and receiving MLV vaccines may have
heterologous types to the vaccines, and molecular tests should be performed to
differentiate field from vaccine strains. Potentially the efficacy of current
PI3V A vaccines should be evaluated with other types such a PI3V B and PI3V C.
PMID- 28416406
TI - Acute Stroke Despite Dabigatran Anticoagulation Treated with Idarucizumab and
Intravenous Tissue Plasminogen Activator.
AB - Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in
patients with nonvalvular atrial fibrillation. For patients who present with an
acute stroke despite dabigatran therapy, clinical data on the use of intravenous
tissue plasminogen activator (IV-tPA) is limited. There is an anticipated
increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in
patients on dabigatran therapy. In 2015, the humanized monoclonal antibody
fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant
effects of dabigatran. Dabigatran reversal with idarucizumab before
administration of IV-tPA might reduce the risk of sICH. We report a case of a 69
year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who
presented with an initial National Institutes of Health Stroke Scale (NIHSS) of
12. There was no early evidence of ischemic stroke or hemorrhage on head computed
tomography, and coagulation studies implied therapeutic dabigatran levels. After
controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA
was administrated beginning 197 minutes after he was last seen at his baseline.
Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the
left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient
was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated
that he was at his prestroke baseline, except for a complaint of worsened short
term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and
should be considered for acute stroke patients arriving in the IV-tPA time
window.
PMID- 28416405
TI - Development, Validation, and Assessment of an Ischemic Stroke or Transient
Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea.
AB - BACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used
routinely to guide clinicians regarding patient referral for polysomnography
(PSG), rely heavily on symptomatology. We sought to develop and validate a
cerebrovascular disease-specific OSA prediction model less reliant on
symptomatology, and to compare its performance with commonly used screening
instruments within a population with ischemic stroke or transient ischemic attack
(TIA). METHODS: Using data on demographic factors, anthropometric measurements,
medical history, stroke severity, sleep questionnaires, and PSG from 2
independently derived, multisite, randomized trials that enrolled patients with
stroke or TIA, we developed and validated a model to predict the presence of OSA
(i.e., Apnea-Hypopnea Index >=5 events per hour). Model performance was compared
with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the
Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age,
Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score.
RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck,
weight [in Pounds], Insulin resistance/diabetes, and National Institutes of
Health Stroke Scale) performed modestly better than other instruments in
identifying patients with OSA, showing reasonable discrimination in the
development (c-statistic .732) and validation (c-statistic .731) study
populations, and having the highest negative predictive value of all in
struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA
screening instruments when making decisions about referral for PSG. The high
negative predictive value of the SLEEP INventory may be useful in determining and
prioritizing patients with stroke or TIA least in need of overnight PSG.
PMID- 28416407
TI - Relationship between Hemorrhagic Complications and Target Vessels in Acute
Thrombectomy.
AB - PURPOSE: Intracranial hemorrhage after thrombectomy using a catheter to treat
acute major cerebral artery occlusion is known to exacerbate patient outcomes.
This study was performed to determine the relationship between middle cerebral
artery (MCA) tortuosity and postoperative hemorrhage. METHODS: We examined 111
consecutive patients who underwent acute thrombectomy for major intracranial
artery occlusion in the anterior circulation at our hospital between September
2013 and June 2016. Patients in whom intracranial hemorrhage or subarachnoid
hemorrhage was seen on head computed tomography 12-24 hours after surgery were
assigned to the hemorrhagic group, whereas all the other patients were assigned
to the nonhemorrhagic group. The groups were compared for tortuosity of the MCA,
which was evaluated by finding the top-to-bottom (TB) distance of the M1 segment
on anterior-posterior view angiograms. A modified Rankin scale score of 0-2 at 3
months after onset was considered a favorable prognosis. RESULTS: The hemorrhagic
group comprised 28 patients (25.2%) and the nonhemorrhagic group comprised 83
patients (74.8%). No significant difference in patient characteristics was seen
between the groups. The hemorrhagic group displayed significantly fewer patients
with a favorable prognosis (17.9% versus 43.4%, P = .016). The TB distance was
significantly greater in the hemorrhagic group (hemorrhagic group, 9.7 mm;
nonhemorrhagic group, 7.6 mm; P = .002); multivariate analysis also identified a
TB distance over 8.8 mm as a factor independently associated with postoperative
intracranial hemorrhage (P = .001). CONCLUSIONS: Post-thrombectomy hemorrhage was
significantly correlated with TB distance. A solution is needed for selecting and
combining devices used in patients with a TB distance over 8.8 mm.
PMID- 28416408
TI - [Description of an isoniazid-resistant tuberculosis outbreak in a block of
apartments].
PMID- 28416409
TI - [Recommendations for the unequivocal identification of the newborn].
AB - Newborn identification is a legal right recognised by international and national
laws. Moreover, improving the accuracy of correct patient identification is an
important goal of patient safety solutions programs. In this article, the
Standards Committee of the Spanish Society of Neonatology establishes
recommendations to ensure correct identification of the newborn whilst in
hospital. Currently, the most reliable method of identification of the newborn is
the combination of identification cord clamp and bracelets (mother bracelet,
newborn bracelet and cord clamp with the same number and identical and exclusive
barcode system for each newborn) and the collection of maternal and umbilical
cord blood samples (for DNA testing only for identification purposes).
PMID- 28416410
TI - Progressive Occlusion and Recanalization After Endovascular Treatment for 287
Unruptured Small Aneurysms (<5mm): A Single-Center 6-Year Experience.
AB - OBJECTIVE: We aimed to investigate the effect of coiling for small unruptured
intracranial aneurysms (UIAs) (<5 mm) on progressive occlusion and
recanalization, and the dubious factors related to progressive occlusion and
recanalization among UIAs without complete occlusion. METHODS: A total of 264
patients with 287 small UIAs were coiled in our institution between June 2009 and
December 2014. All UIAs were divided into small (3-5 mm) and very small (<3 mm)
groups, and UIAs without initial complete occlusion were divided into
progressive, stable, and recanalization groups. Baseline characteristics,
procedure-related complications, angiographic follow-up results, and clinical
outcomes were statistically analyzed. RESULTS: Among 287 aneurysms, 211 aneurysms
(73.5%) were completely coiled, 3 (1.2%) had intraoperative ruptures, and 12
(4.2%) had perioperative thromboembolic events. Angiographic follow-up was
available for 174 patients (65.9%), and the incidence of recanalization was 5.7%.
Among 56 aneurysms without complete occlusion, 43 (76.8%) had progressive
occlusion and 6 (10.7%) had recanalization. Anatomic results of initial and
follow-up between the small and very small groups were similar. On logistic
regression analysis, smaller size (<3 mm) without complete occlusion related to
recanalization (odds ratio, 8.0, 95% confidence interval 1.3-50.0; P = 0.026).
CONCLUSIONS: Our study suggested that coil embolization of small UIAs can achieve
a high rate of progressive occlusion and a low rate of recanalization during
follow-up. Anatomic results of initial and follow-up between small (3-5 mm) and
very small (<3 mm) groups were similar. Smaller size (<3 mm), without complete
occlusion, may relate to recanalization.
PMID- 28416411
TI - Awake High-Flow Extracranial to Intracranial Bypass for Complex Cerebral
Aneurysms: Institutional Clinical Trial Results.
AB - OBJECTIVE: Assess the potential added benefit to patient outcomes of "awake"
neurological testing when compared with standard neurophysiologic testing
performed under general endotracheal anesthesia. METHODS: Prospective study of 30
consecutive adult patients who underwent awake high flow extracranial to
intracranial (HFEC-IC) bypass. Clinical neurological and neurophysiologic
findings were recorded. Primary outcome measures were the incidence of
stroke/cerebrovascular accident (CVA), length of stay, discharge to
rehabilitation, 30-day modified Rankin scale score, and death. An analysis was
also performed of a retrospective control cohort (n = 110 patients who underwent
HFEC-IC for internal carotid artery (ICA) aneurysms under standard general
endotracheal anesthesia). RESULTS: Five patients (16.6%) developed clinical awake
neurological changes (4, contralateral hemiparesis; 1, ipsilateral visual
changes) during the 10-minute ICA occlusion test. These patients had 2 kinks in
the graft, 1 vasospasm, 1 requiring reconstruction of the distal anastomosis, and
1 developed blurring of vision that reversed after the removal of the distal
permanent clip on the ICA. Three of these 5 patients had asynchronous clinical
"awake" neurological and neurophysiologic changes. Two patients (7%) developed
CVA. Median length of stay was 4 days. Twenty-eight of 30 patients were
discharged to home. Median modified Rankin scale score was 1. There were no
deaths in this series. Absolute risk reduction in the awake craniotomy group (n =
30) relative to control retrospective group (n = 110) was 7% for CVA, 9% for
discharge to rehabilitation, and 10% for graft patency. CONCLUSIONS: Temporary
ICA occlusion during HFEC-IC bypass for ICA aneurysms in conjunction with awake
intraoperative clinical testing was effective in detecting a subset of patients
(n = 3, 10%) in whom neurological deficit was not detected by neurophysiologic
monitoring alone.
PMID- 28416412
TI - Successful Treatment of Symptomatic Intracranial Carotid Artery Stenosis Using a
24-mm Long Bare Metal Coronary Stent.
AB - BACKGROUND: Intracranial arterial atherosclerosis represents a common cause of
stroke. Despite aggressive and optimal medical management, many patients will
unfortunately suffer additional cerebrovascular events. The role of endovascular
intervention for intracranial atherosclerotic disease continues to be uncertain,
particularly in regard to extensive, symptomatic stenosis. CASE DESCRIPTION: We
present a case of a 42-year-old man with a complex medical history who presented
with recurrent ischemic stroke in the ipsilateral hemisphere despite optimal
medical management. Given the length of stenosis and the luminal size of the
intracranial cavernous and petrous segments of the internal carotid artery, we
used a bare metal coronary stent (4.0 mm * 24 mm). This represents one of the
longest stents deployed for intracranial disease reported in the literature.
CONCLUSIONS: This case illustrates that a long coronary stent might be
successfully used to manage extensive intracranial lesions. We also review the
efficacy of using 1 very long stent versus multiple overlapping stents, with
reference to the coronary angiography literature.
PMID- 28416413
TI - Evaluation of the PhysioTelTM Digital M11 cardiovascular telemetry implant in
socially housed cynomolgus monkeys up to 16weeks after surgery.
AB - INTRODUCTION: The novel PhysioTelTM Digital M11 telemetry implant was evaluated
in socially housed monkeys with respect to both safety pharmacological
cardiovascular (arterial blood pressure (BP), heart rate (HR) and
electrocardiogram (ECG)) and toxicological (clinical pathology and
histopathology) endpoints. METHODS: Telemetry and clinical pathology data were
obtained repeatedly up to 16weeks after surgery in four female cynomolgus
monkeys, followed by necropsy. Due to postsurgical complications, one spare
animal was included and only toxicological endpoints from the affected (fifth
animal) were reported. Continuous telemetry recordings were conducted at periods
without dosing and after ascending doses of moxifloxacin (0, 10, 30, 100mg/kg)
and L-NAME (0, 0.1, 1, 10mg/kg). Additionally, a retrospective power analysis was
conducted based on baseline M11 implant data from 32 other animals. RESULTS:
During periods without dosing, the cardiovascular endpoints were stable over time
and within normal ranges. Moxifloxacin and L-NAME elicited the expected
pharmacological responses with dose-dependent increase in QTca (8, 17, 22ms) and
BP (mean BP: 12, 21, 34mmHg), respectively. Expected intravascular and tissue
reactions were observed at the sites of the BP catheter and the transmitter.
Signs of infection (localised to the transmitter implantation site with
associated systemic effects) was noted in the fifth animal. No systemic
pathologies were seen in any animals. Power analysis (80% power) indicated that
the minimal differences which can be detected in a parallel group design (n=6)
are 7mmHg (mean BP), 16bpm (HR), 12ms (QTca). DISCUSSION: The M11 implant
provided stable, high quality ECG and BP data for a duration covering the length
of sub-chronic repeated dose toxicity studies without important impact on
toxicological endpoints. Adequate power in order to elucidate major treatment
related cardiovascular effects was demonstrated. However to avoid post-surgical
complications the implantation procedures should be carefully considered before
using the method.
PMID- 28416414
TI - Deep temporal models and active inference.
AB - How do we navigate a deeply structured world? Why are you reading this sentence
first - and did you actually look at the fifth word? This review offers some
answers by appealing to active inference based on deep temporal models. It builds
on previous formulations of active inference to simulate behavioural and
electrophysiological responses under hierarchical generative models of state
transitions. Inverting these models corresponds to sequential inference, such
that the state at any hierarchical level entails a sequence of transitions in the
level below. The deep temporal aspect of these models means that evidence is
accumulated over nested time scales, enabling inferences about narratives (i.e.,
temporal scenes). We illustrate this behaviour with Bayesian belief updating -
and neuronal process theories - to simulate the epistemic foraging seen in
reading. These simulations reproduce perisaccadic delay period activity and local
field potentials seen empirically. Finally, we exploit the deep structure of
these models to simulate responses to local (e.g., font type) and global (e.g.,
semantic) violations; reproducing mismatch negativity and P300 responses
respectively.
PMID- 28416415
TI - Age-dependent variation of fecal calprotectin in cystic fibrosis and healthy
children.
AB - BACKGROUND: Fecal calprotectin may be used as a non-invasive method to assess the
effect of novel therapies on the gut in cystic fibrosis (CF). METHOD: Stools from
CF patients and healthy controls (HC) (0-10years old) were prospectively
collected for evaluation of temporal trends. RESULTS: 130 CF samples (64
subjects) and 114 HC samples (101 subjects) were collected. Overall, fecal
calprotectin levels were different in CF patients and HC from 0 to 10years
(P=0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to
1years (P=0.03) and demonstrated an upward trajectory until 4years. From >4 to
10years calprotectin was consistently higher in CF patients compared with HC
(P=0.007). CONCLUSIONS: Fecal calprotectin levels in children with CF and HC were
age-dependent and had distinct trajectories. Careful interpretation of
calprotectin is required if used in drug trials for CF, particularly in children
less than 4years old.
PMID- 28416416
TI - Flow Function of Pharmaceutical Powders Is Predominantly Governed by Cohesion,
Not by Friction Coefficients.
AB - The purpose of this study was to demonstrate that the flow function (FFc) of
pharmaceutical powders, as measured by rotational shear cell, is predominantly
governed by cohesion but not friction coefficients. Driven by an earlier report
showing an inverse correlation between FFc and the cohesion divided by the
corresponding pre-consolidation stress (Wang et al. 2016. Powder Tech. 294:105
112), we performed analysis on a large data set containing 1130 measurements from
a ring shear tester and identified a near-perfect inverse correlation between the
FFc and cohesion. Conversely, no correlation was found between FFc and friction
angles. We also conducted theoretical analysis and estimated such correlations
based on Mohr-Coulomb failure model. We discovered that the correlation between
FFc and cohesion can sustain as long as the angle of internal friction at
incipient flow is not significantly larger than the angle of internal friction at
steady-state flow, a condition covering almost all pharmaceutical powders. The
outcome of this study bears significance in pharmaceutical development. Because
the cohesion value is strongly influenced by the interparticle cohesive forces,
this study effectively shows that it is more efficient to improve the
pharmaceutical powder flow by lowering the interparticle cohesive forces than by
lowering the interparticle frictions.
PMID- 28416418
TI - Current Progress Toward a Better Understanding of Drug Disposition Within the
Lungs: Summary Proceedings of the First Workshop on Drug Transporters in the
Lungs.
AB - The School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin
hosted the "1st Workshop on Drug Transporters in the Lungs" in September 2016 to
discuss the impact of transporters on pulmonary drug disposition and their roles
as drug targets in lung disease. The workshop brought together about 30
scientists from academia and pharmaceutical industry from Europe and Japan and
addressed the primary questions: What do we know today, and what do we need to
know tomorrow about transporters in the lung? The 3 themes of the workshop were:
(1) techniques to study drug transporter expression and actions in the lungs; (2)
drug transporter effects on pulmonary pharmacokinetics-case studies; and (3)
transporters as drug targets in lung disease. Some of the conclusions of the
workshop were: suitable experimental models that allow studies of transporter
effects are available; data from these models convincingly show a contribution of
both uptake and efflux transporters on pulmonary drug disposition; the effects of
transporters on drug lung PK is now better conceptualized; some transporters are
associated with lung diseases. However, more work is needed to establish which of
the available models best translate to the clinical situation.
PMID- 28416417
TI - In Vitro Evaluation of Nasogastric Tube Delivery Performance of Esomeprazole
Magnesium Delayed-Release Capsules.
AB - Enteral feeding tubes are used to deliver food or drugs to patients who cannot
swallow. To deliver delayed-release drugs that are formulated as enteric coated
granules to these patients via feeding tubes requires that they be suspended in
water before administration. Importantly, the suspension of enteric granules in
water of varying pH can cause damage to the enteric coating and affect the
bioavailability of the drug. Here, analytical methods for testing acid resistance
stability and particle size distribution (PSD) of esomeprazole granules were used
to monitor the integrity of the granule enteric coating after water pretreatment
and delivery through an oral syringe and nasogastric (NG) tube. Granules from
esomeprazole magnesium delayed-release capsules were transferred to an oral
syringe, suspended in water, and delivered on the bench through an NG tube.
Subsequently, acid resistance stability (i.e., the amount of drug released after
2-h acid dissolution) was determined via high-performance liquid chromatography,
and the PSD were measured with a laser diffraction system. All the granules
demonstrated acid resistance stability when the granules were delivered
immediately (0 min incubation) through the oral syringe and NG tube. In contrast,
some granules demonstrated significant drug release during acid exposure after a
15-min incubation period which mimics a possible delay in delivery of the drug
from the syringe by the caregiver. A bimodal PSD was observed with these
granules, which was attributed to debris from damaged enteric coating and
particle agglomeration. The methods developed in this study could be used to
distinguish batches with suboptimal product quality for delivery using NG tubes
and to confirm the substitutability of generic drug products for this alternative
route of administration.
PMID- 28416419
TI - Evaluation of Renal Transporter Inhibition Using Creatinine as a Substrate In
Vitro to Assess the Clinical Risk of Elevated Serum Creatinine.
AB - Creatinine is a widely accepted biomarker for renal toxicity, but its renal
clearance via transporter-mediated active secretion is significant. For a given
new chemical entity, therefore, elevations in serum creatinine (SCr) can be
caused by the inhibition of renal transporter(s) without renal toxicity. In the
present study, an effort was made to assess the correlation between the
inhibition of renal transporters in vitro and elevations in SCr. A total of 15
compounds were chosen based on their known effect on SCr and minimal impact on
glomerular filtration rate. Their inhibition potencies against the major
creatinine renal transporters, including organic cation transporter 2, organic
anion transporter 2, and 2 forms of multidrug and toxin extrusion (MATE1 and
MATE2K), were assessed in transporter-transfected cell lines using creatinine as
a probe substrate. Collectively, the data suggest that the observed elevations in
SCr can be attributed to the inhibition of renal transporter(s), but inhibition
of renal transporters does not necessarily lead to elevated SCr. Thus, renal
transporter inhibition data can be used to rationalize SCr changes. Additionally,
differing renal transporter inhibition potencies using creatinine and metformin
as probe substrates suggest that substrate-dependent inhibition exists for some
compounds.
PMID- 28416421
TI - [Endoscopy is not so two-dimensional and microsurgery not so three-dimensional].
PMID- 28416420
TI - Identification of Endogenous Biomarkers to Predict the Propensity of Drug
Candidates to Cause Hepatic or Renal Transporter-Mediated Drug-Drug Interactions.
AB - Drug transporters expressed in liver and kidney play a critical role in the
elimination of a wide range of drugs and xenobiotics and inhibition of these
transporters may therefore cause clinically significant drug-drug interactions
(DDIs). Currently, in vitro transporter inhibition data are used to assess the
risk that a drug candidate may act as an inhibitor of a transporter in patients
at clinically relevant exposures. However, this approach is hampered by low
confidence in in vitro to in vivo extrapolations, and large inter-system and
inter-laboratory variability in in vitro data. Several endogenous compounds have
been identified as substrates of drug transporters. Determining the impact of
perpetrator drugs on the plasma or urinary exposure of these potential endogenous
biomarkers in humans is being explored as an alternative approach to assess the
DDI liability of drug candidates, especially in early drug development. In this
review, we provide an overview of recently identified biomarkers used to study
the inhibition of hepatic and renal transporters; summarize the methods and
strategies employed to identify biomarkers; and discuss the utility, limitation,
and future direction of biomarker approaches to predict transporter-mediated
DDIs.
PMID- 28416422
TI - [Penetrating air gun pellet into the orbital apex].
AB - A foreign body penetrating into the intraconal orbital compartment poses a
surgical challenge because of its deep location behind the globe and near the
optic nerve. We present a case of an air gun pellet lodged into the orbital apex,
which was removed via superolateral orbitotomy through coronal incision. This
additional craniofacial technique is a safe procedure to access the lateral
aspect of the intraconal compartment in the unusual event of having to remove an
orbital foreign body.
PMID- 28416423
TI - Dietary administration of sodium alginate ameliorated stress and promoted immune
resistance of grouper Epinephelus coioides under cold stress.
AB - Grouper, Epinephelus coioides, fed a diet containing sodium alginate at 0
(control, named C) and 1.0 g kg-1 (named S) at a temperature of 28 degrees C for
12 days, were then further individually transferred to 28 (two groups named C-28
and S-28) or 20 degrees C (two groups named C-20 and S-20), and immune
parameters and stress indexes were measured at the beginning and after 6, 12, 24
and 48 h of exposure. Examination of immune parameters revealed that the
alternative complement activity (ACH50), lysozyme activity, phagocytic activity,
superoxide dismutase, and respiratory bursts significantly increased in groupers
fed the sodium alginate-containing diet for 12 days, and were higher in the S-28
than those of the C-28 and S-20 groups, which were higher than those of the C-20
group from 6 to 48 h except for ACH50 at 48 h, respiratory bursts at 48 h, and
lysozymes at 6 h. For the assessment of stress indicators, cortisol, glucose, and
lactate levels of serum significantly decreased in grouper fed the sodium
alginate-containing diet for 12 days, and were higher in the C-20 group than
those of the C-28 and S-20 groups, which were higher than those of the S-20 group
at 6-48 h. In another experiment, grouper fed the test diet for 12 days at a
temperature of 28 degrees C were challenged with Photobacterium damselae subsp.
piscicida at a dose of 5 * 103 colony-forming units (cfu) (g fish)-1, and then
individually transferred to 28 or 20 degrees C. The survival rate of challenged
fish of the C-28 group was significantly lower than those of challenged fish of
the C-20 and S-28 groups, which were significantly lower than that of challenged
fish of the S-20 group. All challenged fish of the S-20 group survived. Survival
rates over 144 h were 30.0%, 70.0%, and 56.7% for the C-28, C-20, and S-28
groups, respectively. Our results indicated that dietary sodium alginate
administration downregulated stress response indicators, enhanced immune
responses, and prevented impacts of physiologic stress responses,
immunosuppression, and susceptibility to P. damselae subsp. piscicida in grouper
subjected to cold stress. Grouper cultured at 28 degrees C were more susceptible
to P. damselae subsp. piscicida infection.
PMID- 28416424
TI - [First requests for a regional pediatric palliative care team: A prospective and
observational study].
AB - INTRODUCTION: In France, 26 regional pediatric palliative care teams (ERRSPP)
were created between 2008 and 2012. We conducted the first prospective French
study to describe the main specifications of the initial contact with an ERRSPP
and to analyze the responses given. DESIGN AND METHODS: All the requests for
interventions on the part of the ERRSPP were collected between September 2013 and
September 2014. We prospectively completed a questionnaire on the patient's
clinical and demographic data (age, sex, disease), details regarding the request
(type of applicant, unit's specialty, request pattern), and the answers provided
(interval between diagnosis and request, duration of care by ERRSPP, death,
changes compared to the initial request). The diseases were classified within one
of the six groups of palliative pediatric care diseases, based on the standards
of the Canadian palliative care association. RESULTS: We gathered 67 requests, 61
relating to patients. The median age at the request was 49.8 months (range: 2.3
145). The original pattern was multiple: multidisciplinary decision-making (42
%), coordination of care (34 %), symptom management (21 %), logistic support for
home care (19 %), education (9 %) and case discussion (6 %). Requests concerning
multidisciplinary decision-making were predominant within the neonatal period (61
%); coordination of care was significant for children and adolescents (78 % after
4 years of age). The study of the median time from diagnosis to request compared
to the groups of diseases revealed a short time in group 5 (neonatology: 0.36
months) and a long time in group 4 (irreversible and nonscalable diseases: 54.6
months) (P<0.001). At the end of the study, the follow-up of 50.8 % of the
patients by ERRSPP was still going on (median duration of care by the ERRSPP of
Languedoc-Roussillon region [ERRSPP-LR], 3.4 months [range: 0.2-5.5]). No request
was formulated by a general practitioner. CONCLUSION: This study shows the
heterogeneity of the initial contact made with an ERRSPP, confirming its
different assignments and the need for a multidisciplinary team. The ERRSPP's
answer was expanded in half of the cases, attesting to the changing needs over
time.
PMID- 28416425
TI - [Bilateral facial nerve palsy associated with Epstein-Barr virus infection in a 3
year-old boy].
AB - Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We
describe a case of bilateral simultaneous facial nerve palsy associated with
Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to
the diagnosis of EBV infection: the clinical situation (fever, stomachache, and
throat infection), white blood cell count (5300/mm3 with 70% lymphocyte count),
seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a
positive blood EBV polymerase chain reaction (9.3*103 copies of EBV-DNA). An MRI
brain scan showed bilateral gadolinium enhancement of the facial nerve. A
treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was
implemented. Antibiotics were stopped after the diagnosis of Lyme disease was
ruled out. The patient's facial weakness improved within a few weeks. Bilateral
facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic
in only 20% of cases. Therefore, it requires further investigation and
examination to search for the underlying etiology. Lyme disease is the first
infectious disease that should be considered in children, especially in endemic
areas. An antibiotic treatment effective against Borrelia burgdorferi should be
set up until the diagnosis is negated or confirmed. Further examination should
include a blood test (such as immunologic testing, and serologic testing for
viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and
an MRI brain scan to exclude any serious or curable underlying etiology. Facial
bilateral nerve palsy associated with EBV is rarely described in children.
Neurological complications have been reported in 7% of all EBV infections. The
facial nerve is the most frequently affected of all cranial nerves. Facial palsy
described in EBV infections is bilateral in 35% of all cases. The physiopathology
is currently unknown. Prognosis is good most of the time.
PMID- 28416426
TI - [The Jarde law, a real simplification of research in France?]
AB - The Jarde law was voted in 2012 and its implementing decrees were published in
November 2016. The delay between the vote and the decrees highlights the
difficulties encountered. This law concerns all research, interventional and
otherwise, involving the human person. Each research study must receive the
approval of a randomly assigned ethics committee or Committee for the Protection
of Persons. The approach here is based on risk in three types of study:
interventional studies, studies with minimal risk and intervention, and non
interventional studies (observational studies). The main changes are: simplified
informed consent for pediatric studies and possible enrolment for people not
affiliated with a social health care system in non-interventional research. The
law provides clarification for changes in the purpose of biological collections.
For vigilance, the notions of "new facts" and "urgent security measures" have
emerged. Although this law appears to be an advancement, some concerns still need
to be clarified. The main problem arises from the foreseeable extension of the
delay to implement research. Medical research is a competition where time is
valuable. Colleagues working on cosmetics research have already anticipated these
difficulties. On February 8, 2017, the decrees of the Jarde law were suspended
for cosmetics studies. Will the Jarde law be suspended for all French clinical
research?
PMID- 28416427
TI - [Femoral Nora lesion in a 5-year-old child].
PMID- 28416429
TI - [Life-threatening sleepwalking (Elpenor's syndrome) in a 10-year-old child].
AB - : Though benign in the majority of cases, sleepwalking sometimes causes injuries
due, among other causes, to falls. Such accidents can be life-threatening - a
situation that has been termed Elpenor syndrome (in reference to an accident
experienced by a character in Homer's epic The Odyssey) - in particular when
entailing defenestration. This syndrome has been described in adults and
adolescents; we report here a case in a child. OBSERVATION: This 10-year-old girl
was admitted at night to our hospital after a 3-m fall at home. She was alert
(Glasgow score, 15) at admission; a frontal wound and a deformation of the right
wrist were noted. Brain CT scans showed a frontal skull fracture and frontal lobe
contusion, wrist x-rays showed a displaced right fracture. The patient underwent
urgent neurosurgery (wound excision and suture after reduction of skull fracture)
and closed reduction and immobilization of the wrist fracture, both under general
anesthesia. She underwent a psychiatric assessment in the intensive care unit 3
days after her fall. She was alert, well-oriented in time and space, and spoke
fluently. She had no memory of her fall, only remembering going to bed in the
evening before the accident and waking up in the ambulance on the way to the
hospital. She displayed no sign of a concurrent mental illness and no suicidal
ideas. Her parents reported that the evening of the accident she and her two
brothers had all fallen asleep about 11:00 pm while watching TV, in the double
bed of the guest room, placed just beside its window. At approximately 1:00 am,
her father, who was going to bed and had just made noise in the hall, heard a cry
from the guest room. He entered the room immediately and saw the opened window
and his daughter lying on the outside ground; the brothers only awakened after
the fall. The family had returned 2 days before from a 6-month stay in the United
States, with jet-lag, sleep deprivation, and a disorganized sleep/wake rhythm in
the patient. There was no medication before the accident, no substance use
(including caffeine), and no concurrent medical problem. Over the 2 preceding
years, the patient had undergone two witnessed episodes of early-nighttime
arousal with altered consciousness and calm wandering (including going downstairs
on one occasion), both strongly suggesting sleepwalking. There was a history of
sleepwalking in her father and her older brother. Life-threatening sleepwalking
(Elpenor syndrome) was diagnosed. The child and her parents were educated about
sleepwalking; regularization of sleep schedules and sleep extension (avoidance of
sleep deprivation, short napping when possible) were prescribed. We also
recommended securing the home (bed, windows, and stairways). No pharmacological
treatment was instituted. During the following 18 months, the child manifested
only one noted sleepwalking episode, without risk-taking. She had no neurological
or psychopathological sequela from her accident, of which she never had a memory.
CONCLUSION: Elpenor syndrome can occur in a child; consequently, it is important
to inform parents of children with sleepwalking about the necessity of always
securing the night-time environment.
PMID- 28416428
TI - [Nasogastric rehydration for treating children with gastroenteritis].
AB - INTRODUCTION: When oral rehydration is not feasible, enteral rehydration via the
nasogastric route has been the ESPGHAN recommended method of rehydration since
2008, rather than intravenous rehydration (IVR), for children with acute
gastroenteritis. However, these recommendations are rarely followed in France.
Since 2011, in case of failure of oral rehydration, enteral rehydration has been
used as a first-line therapy in the Children's Emergency Department at the
Grenoble-Alpes University Hospital. PURPOSE: The aims of the study were to
compare the length of the hospital stay, the duration of initial rehydration, and
the incidence of complications and failure with the use of enteral nasogastric
versus intravenous rehydration. METHODS: This study compared two cohorts of
children (<3 years of age) with mild-to-moderate dehydration caused by acute
gastroenteritis and failure of rehydration via the oral route. The first group
(winter 2010-2011) was managed according to the previous protocol (intravenous
rehydration). The second group (winter 2011-2012) was managed according the new
protocol (nasogastric tube rehydration [NGR]). The rest of the gastroenteritis
management was identical in both groups. RESULTS: A total of 132 children were
included, 65 were treated with nasogastric tube rehydration (NGR) and 67 with
intravenous rehydration. There was a significant reduction in the duration of
hospitalization in the post-emergency unit in the NGR group: 23.6h vs 40.1h
(P<0.05). The duration of initial rehydration was also significantly reduced
(10.5h vs 22.0h). There was no significant difference regarding serious adverse
events. However, the NGR group presented more mild adverse events (22 vs 7,
P<0.05) and more treatment failures (15.3% vs 3%, P=0.013). CONCLUSION:
Nasogastric rehydration reduces the duration of rehydration and the length of the
hospital stay without increasing the incidence of serious adverse events for
dehydrated children hospitalized for acute gastroenteritis.
PMID- 28416430
TI - [Extracorporeal membrane oxygenation in critically ill neonates and children].
AB - Extracorporeal membrane oxygenation is used as a last resort during neonatal and
pediatric resuscitation in case of refractory circulatory or respiratory failure
under maximum conventional therapies. Different types of ECMO can be used
depending on the initial failure. The main indications for ECMO are refractory
respiratory failure (acute respiratory distress syndrome, status asthmaticus,
severe pneumonia, meconium aspiration syndrome, pulmonary hypertension) and
refractory circulatory failure (cardiogenic shock, septic shock, refractory
cardiac arrest). The main contraindications are a gestational age under 34 weeks
or birth weight under 2kg, severe underlying pulmonary disease, severe immune
deficiency, a neurodegenerative disease and hereditary disease of hemostasis.
Neurological impairment can occur during ECMO (cranial hemorrhage, seizure or
stroke). Nosocomial infections and acute kidney injury are also frequent
complications of ECMO. The overall survival rate of ECMO is about 60 %. This
survival rate can change depending on the initial disease: from 80 % for meconium
aspiration syndrome to less than 10 % for out-of-hospital refractory cardiac
arrest. Recently, mobile ECMO units have been created. These units are able to
perform ECMO out of a referral center for untransportable critically ill
patients.
PMID- 28416431
TI - [Atypical osteochondroma in a 5-year-old child].
PMID- 28416432
TI - [Transverse reductional anomaly and atypical fibrodysplasia ossificans
progressiva: A case diagnosed late].
AB - Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by
the association of congenital bone abnormalities and extraskeletal ossification
flare-ups occurring in muscles and fasciae. Early diagnosis is important to
prevent ossification flare-ups, but some atypical presentations can lead to
errors in diagnosis and therefore delay. Here, we report on a case of an atypical
presentation of FOP in a girl, in whom prominent transverse reductional
abnormalities delayed diagnosis. The patient developed extraskeletal
ossifications and progressive fibrosis that led to motor restrictions. Since
early diagnosis is important, we discuss the clinical presentations of FOP and
the differential diagnoses.
PMID- 28416433
TI - Addressing the Hidden Burden of Malnutrition for Hospitalized Patients.
PMID- 28416434
TI - Malnutrition Diagnosis during Adult Inpatient Hospitalizations: Analysis of a
Multi-Institutional Collaborative Database of Academic Medical Centers.
AB - BACKGROUND: Malnutrition is a significant problem for hospitalized patients.
However, the true prevalence of reported malnutrition diagnosis in real-world
clinical practice is largely unknown. Using a large collaborative multi
institutional database, the rate of malnutrition diagnosis was assessed and used
to assess institutional variables associated with higher rates of malnutrition
diagnosis. OBJECTIVE: The aim of this study was to define the prevalence of
malnutrition diagnosis reported among inpatient hospitalizations. DESIGN: The
University Health System Consortium (Vizient) database was retrospectively
reviewed for reported rates of malnutrition diagnosis. PARTICIPANTS/SETTING: All
adult inpatient hospitalization at 105 member institutions during fiscal years
2014 and 2015 were evaluated. MAIN OUTCOME MEASURES: Malnutrition diagnosis based
on the presence of an International Classification of Diseases-Ninth Revision
diagnosis code. STATISTICAL ANALYSIS: Hospital volume and publicly available
hospital rankings and patient satisfaction scores were obtained. Multiple
regression analysis was performed to assess the association between these
variables and reported rates of malnutrition. RESULTS: A total of 5,896,792
hospitalizations were identified from 105 institutions during the 2-year period.
It was found that 292,754 patients (5.0%) had a malnutrition diagnosis during
their hospital stay. By institution, median rate of malnutrition diagnosis during
hospitalization was 4.0%, whereas the rate of severe malnutrition diagnosis was
0.9%. There was a statistically significant increase in malnutrition diagnosis
from 4.0% to 4.9% between 2014 and 2015 (P<0.01). Institutional factors
associated with increased diagnosis of malnutrition were higher hospital volume,
hospital ranking, and patient satisfaction scores (P<0.01). CONCLUSIONS: Missing
a malnutrition diagnosis appears to be a universal issue because the rate of
malnutrition diagnosis was consistently low across academic medical centers.
Institutional variables were associated with the prevalence of malnutrition
diagnosis, which suggests that institutional culture influences malnutrition
diagnosis. Quality improvement efforts aimed at improved structure and process
appear to be needed to improve the identification of malnutrition.
PMID- 28416435
TI - Omics and cytokine discovery in fish: Presenting the Yellowtail kingfish (Seriola
lalandi) as a case study.
AB - A continued programme of research is essential to overcome production bottlenecks
in any aquacultured fish species. Since the introduction of genetic and molecular
techniques, the quality of immune research undertaken in fish has greatly
improved. Thousands of species specific cytokine genes have been discovered,
which can be used to conduct more sensitive studies to understand how fish
physiology is affected by aquaculture environments or disease. Newly available
transcriptomic technologies, make it increasingly easier to study the
immunogenetics of farmed species for which little data exists. This paper reviews
how the application of transcriptomic procedures such as RNA Sequencing (RNA-Seq)
can advance fish research. As a case study, we present some preliminary findings
using RNA-Seq to identify cytokine related genes in Seriola lalandi. These will
allow in-depth investigations to understand the immune responses of these fish in
response to environmental change or disease and help in the development of
therapeutic approaches.
PMID- 28416436
TI - Molecular cloning of chicken interleukin-17B, which induces proinflammatory
cytokines through activation of the NF-kappaB signaling pathway.
AB - Interleukin (IL)-17B is a little known member of the IL-17 cytokine family, which
plays an important role in immunity by regulating the expression of
proinflammatory cytokines. In this study, we determined the coding sequence and
biological functions of a novel chicken IL-17B (chIL-17B). The full-length chIL
17B coding sequence includes 567 nucleotides encoding 188 amino acids, which was
identified in small intestinal epithelial cells. The chIL-17B protein shares
96.48% amino acid sequence identity with turkey, 92.57% with duck, and 44.92
64.06% with mammalian IL-17B proteins. ChIL-17B shares three exons and two
introns with mammals, turkey, and duck. Moreover, IL-17B mRNA was more highly
expressed than IL-17A mRNA in several organs of chickens infected with Salmonella
and was upregulated in chicken cell lines following LPS stimulation. In addition,
in chicken cell lines, chIL-17B induced the mRNA expression of several
proinflammatory cytokines, including IL-1beta, IL-6, LITAF, and INF-gamma, but
not IL-17A, and activated MyD88, TAK1, NF-kappaB1, and SOCS1, which are
associated with the NF-kappaB signaling pathway. Taken together, chicken
interleukin-17B plays a critical role in host defense against the bacterial
pathogens, and regulates proinflammatory cytokines by activating the NF-kappaB
signaling pathway.
PMID- 28416437
TI - The computed tomography-based fractal analysis of trabecular bone structure may
help in detecting decreased quality of bone before urgent spinal procedures.
AB - BACKGROUND CONTEXT: To date, no reliable method is available to determine the
parameters of bone density based on the routine spinal computed tomography (CT)
in the emergency setup. We propose the use of fractal analysis to detect patients
with poor quality of bone before urgent or semi-urgent spinal procedures.
PURPOSE: This study aimed to validate the hypothesis that the CT-based fractal
analysis of the trabecular bone structure may help in detecting patients with
poor quality of bone before urgent spinal procedures. STUDY DESIGN: This is a
retrospective analysis of prospectively collected data. METHODS: Patients in whom
the dual-energy x-ray absorptiometry (DEXA) scan and lumbar spine CT were
performed at an interval of no more than 3 months were randomly selected from a
prospectively collected database. Diagnostic axial CT scans of L2, L3, and L4
vertebrae were processed to determine the fractal dimension (FD) of the
trabecular structure of each spinal level. Box-count method and ImageJ 1.49
software were used. The FD was compared with the results of the DEXA scan: bone
mineral density (BMD) and T-score by mean of correlation coefficients. Receiver
operating characteristic curve analysis was later performed to determine the
cutoff value of FD. RESULTS: A total of 102 vertebral levels obtained from 35
patients (mean age 60+/-18 years; 29 female) were analyzed. The FD was
significantly higher in the group of patients with decreased bone density (DBD)
(T-score<-1.0) (1.67 vs. 1.43; p<.0001) and negatively correlated with BMD (R
Spearman, -0.53; p<.0001) and T-score (-0.49; p<.0001). Receiver operating
characteristic curve analysis revealed that a cutoff value of FD>1.53 indicates
DBD (p<.0001; area under the ROC curve [AUC], 0.84; 95% confidence interval [CI],
0.76-0.91). CONCLUSIONS: This study shows that fractal analysis of the lumbar
spine CT images may be used to determine bone density before spinal
instrumentation (eg, metastatic or traumatic cord compression). Further
prospective studies comparing results of the fractal analysis of CT scans with
quantitative CT (qCT) are warranted.
PMID- 28416439
TI - Clinical and radiographic outcomes of bilateral decompression via a unilateral
approach with transforaminal lumbar interbody fusion for degenerative lumbar
spondylolisthesis with stenosis.
AB - BACKGROUND CONTEXT: Laminectomy with posterior lumbar interbody fusion (PLIF) has
been shown to achieve satisfactory clinical outcomes, but it leads to potential
adverse consequences associated with extensive disruption of posterior bony and
soft tissue structures. PURPOSE: This study aimed to compare the clinical and
radiographic outcomes of bilateral decompression via a unilateral approach (BDUA)
with transforaminal lumbar interbody fusion (TLIF) and laminectomy with PLIF in
the treatment of degenerative lumbar spondylolisthesis (DLS) with stenosis. STUDY
DESIGN: This is a prospective cohort study. PATIENT SAMPLE: This study compared
43 patients undergoing BDUA+TLIF and 40 patients undergoing laminectomy+PLIF.
OUTCOME MEASURES: Visual analog scale (VAS) for low back pain and leg pain,
Oswestry Disability Index (ODI), and Zurich Claudication Questionnaire (ZCQ)
score. METHODS: The clinical outcomes were assessed, and intraoperative data and
complications were collected. Radiographic outcomes included slippage of the
vertebra, disc space height, segmental lordosis, and final fusion rate. This
study was supported by a grant from The National Natural Science Foundation of
China (81572168). RESULTS: There were significant improvements in clinical and
radiographic outcomes from before surgery to 3 months and 2 years after surgery
within each group. Analysis of leg pain VAS and ZCQ scores showed no significant
differences in improvement between groups at either follow-up. The mean
improvements in low back pain VAS and ODI scores were significantly greater in
the BDUA+TLIF group than in the laminectomy+PLIF group. No significant difference
was found in the final fusion rate at 2-year follow-up. The BDUA+TLIF group had
significantly less blood loss, shorter length of postoperative hospital stay, and
lower complication rate compared with the laminectomy+PLIF group. CONCLUSIONS:
When compared with the conventional laminectomy+PLIF procedure, the BDUA+TLIF
procedure achieves similar and satisfactory effects of decompression and fusion
for DLS with stenosis. The BDUA+TLIF procedure appears to be associated with less
postoperative low back discomfort and quicker recovery.
PMID- 28416438
TI - NSAID use in intervertebral disc degeneration: what are the effects on matrix
homeostasis in vivo?
AB - BACKGROUND CONTEXT: Non-steroidal anti-inflammatory drugs (NSAIDs) are a widely
used treatment for low back pain (LBP). Literature on NSAID use in articular
cartilage has shown detrimental effects; however, minimal data exist to detail
the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a
major cause of LBP, we explored the effects of indomethacin, a commonly used
NSAID, on disc matrix homeostasis in an animal model of IDD. PURPOSE: This study
aimed to determine the effects of oral indomethacin administration on IDD in an
in vivo rabbit model. This study hypothesized that indomethacin use would
accelerate the progression of IDD based upon serial imaging and tissue outcomes.
STUDY DESIGN/SETTING: This was a laboratory-based, controlled, in vivo evaluation
of the effects of oral indomethacin administration on rabbit intervertebral
discs. METHODS: Six skeletally mature New Zealand white rabbits were divided into
two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture
plus indomethacin (Punc+Ind group). The Punc+Ind group received daily
administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging
(MRI) was obtained at 0, 4, 8, and 12 weeks. The MRI index and the nucleus
pulposus (NP) area were calculated. Discs were harvested at 12 weeks for
determination of disc glycosaminoglycan (GAG) content, relative gene expression
measured by real-time polymerase chain reaction, and histologic analyses.
RESULTS: The MRI index and the NP area of punctured discs in the Punc+Ind group
demonstrated no worsening of degeneration compared with the Puncture group.
Histologic analysis was consistent with less severe disc degeneration in the
Punc+Ind group. Minimal differences in gene expression of matrix genes were
observed between Puncture and Punc+Ind groups. The GAG content was higher in
animals receiving indomethacin in both annulus fibrosus and NP at adjacent
uninjured discs. CONCLUSIONS: Oral indomethacin administration did not result in
acceleration of IDD in an in vivo rabbit model. Future research is needed to
ascertain long-term effects of indomethacin and other NSAIDs on disc matrix
homeostasis.
PMID- 28416440
TI - Inhibition of the PI3K-Akt-mTOR signaling pathway in T lymphocytes in patients
with active tuberculosis.
AB - OBJECTIVES: To investigate PI3K-Akt-mTOR signaling pathway changes and the
proliferation of FoxP3+Treg cells in patients with active tuberculosis. METHODS:
We isolated PBMCs and CD4+CD25+FoxP3+Treg cells from peripheral blood collected
from patients with active tuberculosis and healthy controls. We compared the
proportion and MFI of PI3K-Akt-mTOR pathway components and PTEN by flow cytometry
using specific cell-surface and intracellular markers. Moreover, we detected the
specific secretory proteins ESAT-6 and Ag85B, cytokines IL-10, TGF-beta1 and IL
35 in serum by ELISA. RESULTS: Compared with healthy controls, the proportions of
CD3+Akt+, CD3+p-Akt+, CD3+mTOR+, CD3+p-mTOR+ and CD3+PTEN+ cells, in the T
lymphocyte population of patients with active tuberculosis, were decreased
(p<0.05), while CD3+FoxP3+ cells were increased (p=0.013). Similarly, for
CD4+CD25+FoxP3+Treg cells, the proportions of Akt+ cells, p-Akt+ cells, mTOR+
cells, p-mTOR+ cells and PTEN+ cells were decreased (p<0.05) in patients with
active tuberculosis. Compared with healthy controls, the levels of ESAT-6 and
Ag85B were higher in patients with active tuberculosis (p<0.001). Levels of IL-10
and TGF-beta1 were higher (p<0.001), whereas the level of IL-35 was lower
(p<0.001). CONCLUSION: The PI3K-Akt-mTOR signaling pathway in T lymphocytes and
CD4+CD25+FoxP3+Treg cells was inhibited, which could explain why M.tuberculosis
can induce FoxP3+Treg cell to expand.
PMID- 28416442
TI - Allopregnanolone decreases interictal spiking and fast ripples in an animal model
of mesial temporal lobe epilepsy.
AB - The objective of this study was to characterize the impact of allopregnanolone, a
neurosteroid that acts as a positive allosteric modulator of synaptic and
extrasynaptic GABAA receptors, on interictal spikes and high-frequency
oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine
model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats
experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment
with allopregnanolone (9.6-12.8 mg/kg/day) on the following day. On day 4 after
SE, video-depth EEG recordings from the hippocampal CA3 subfield and the
entorhinal cortex were initiated and continued for 12 consecutive days. We found
that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6%
(2/7) of allopregnanolone-treated animals. Interictal spikes occurred less
frequently in the CA3 subfield of allopregnanolone-treated rats (n = 4) than in
untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous
seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to
both untreated groups (p < 0.05). Finally, allopregnanolone-treated rats had
significantly lower rates of interictal spikes with fast ripples (250-500 Hz)
compared to untreated animals but only in CA3 (p < 0.05). Our findings show that
allopregnanolone reduces the frequency of interictal spikes and fast ripples in
CA3, a structure that plays an important role in ictogenesis and epileptogenesis.
Neurosteroids may therefore influence pathological network activity leading to
spontaneous seizures following pilocarpine-induced SE. Recordings after
termination of allopregnanolone treatment will be however required to establish
whether allopregnanolone exerts disease-modifying properties.
PMID- 28416441
TI - Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct
ligated rat model.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Glechoma
hederacea is frequently prescribed to patients with cholelithiasis, dropsy,
abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main
bioactive components of Glechoma hederacea. AIM OF THE STUDY: This study was
aimed to investigate the hepatoprotective potential of hot water extract of
Glechoma hederacea against cholestatic liver injury in rats. MATERIALS AND
METHODS: Cholestatic liver injury was produced by ligating common bile ducts in
Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were
orally administrated using gastric gavages. Liver tissues and bloods were
collected and subjected to evaluation using histological, molecular, and
biochemical approaches. RESULTS: Using a rat model of cholestasis caused by bile
duct ligation (BDL), daily oral administration of Glechoma hederacea hot water
extracts showed protective effects against cholestatic liver injury, as evidenced
by the improvement of serum biochemicals, ductular reaction, oxidative stress,
inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced
transforming growth factor beta-1 (TGF-beta1), connective tissue growth factor,
and collagen expression, and the anti-fibrotic effects were accompanied by
reductions in alpha-smooth muscle actin-positive matrix-producing cells and
Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory
cell infiltration/accumulation, NF-kappaB and AP-1 activation, and inflammatory
cytokine production. Further studies demonstrated an inhibitory effect of
Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll
like receptor-4 (TLR4) intracellular signaling pathways. CONCLUSIONS: The
hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of
Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of
daily Glechoma hederacea extracts supplementation were associated with anti
oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down
regulation of NF-kappaB, AP-1, and TGF-beta/Smad signaling, probably via
interference with the HMGB1/TLR4 axis.
PMID- 28416444
TI - The pharmacology of voltage-gated sodium channel activators.
AB - Toxins and venom components that target voltage-gated sodium (NaV) channels have
evolved numerous times due to the importance of this class of ion channels in the
normal physiological function of peripheral and central neurons as well as
cardiac and skeletal muscle. NaV channel activators in particular have been
isolated from the venom of spiders, wasps, snakes, scorpions, cone snails and sea
anemone and are also produced by plants, bacteria and algae. These compounds have
provided key insight into the molecular structure, function and
pathophysiological roles of NaV channels and are important tools due to their at
times exquisite subtype-selectivity. We review the pharmacology of NaV channel
activators with particular emphasis on mammalian isoforms and discuss putative
applications for these compounds. This article is part of the Special Issue
entitled 'Venom-derived Peptides as Pharmacological Tools.'
PMID- 28416443
TI - Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.
AB - Astrocytes possess many of the same signalling molecules as neurons. However, the
role of astrocytes in information processing, if any, is unknown. Using
electrophysiological and imaging methods, we report the first evidence that
astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found
that mGlu2 receptor activity reduces inhibitory transmission from the thalamic
reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC
frequencies in VB slices were reduced by the Group II mGlu receptor agonist
LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM)
LY487379 co-application (30 nM LY354740: 10.0 +/- 1.6% reduction; 30 nM LY354740
& 30 MUM LY487379: 34.6 +/- 5.2% reduction). We then showed activation of mGlu2
receptors on astrocytes: astrocytic intracellular calcium levels were elevated by
the Group II agonist, which were further potentiated upon mGlu2 PAM co
application (300 nM LY354740: ratio amplitude 0.016 +/- 0.002; 300 nM LY354740 &
30 MUM LY487379: ratio amplitude 0.035 +/- 0.003). We then demonstrated mGlu2
dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses
to vibrissae stimulation trains were disinhibited by the Group II agonist and the
mGlu2 PAM (LY354740: 156 +/- 12% of control; LY487379: 144 +/- 10% of control).
Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91
+/- 5% of control), suggesting the mGlu2 component to the Group II effect can be
attributed to activation of mGlu2 receptors localised on astrocytic processes
within the VB. Gating of thalamocortical function via astrocyte activation
represents a novel sensory processing mechanism. As this thalamocortical
circuitry is important in discriminative processes, this demonstrates the
importance of astrocytes in synaptic processes underlying attention and
cognition.
PMID- 28416445
TI - alphaO-Conotoxin GeXIVA disulfide bond isomers exhibit differential sensitivity
for various nicotinic acetylcholine receptors but retain potency and selectivity
for the human alpha9alpha10 subtype.
AB - Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct
neuropharmacological properties that are involved in a range of neuropathological
conditions, including pain, addiction, epilepsy, autism, schizophrenia,
Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types
of cancer. The alpha9alpha10 nAChR is a potential target in chronic pain, wound
healing, the pathophysiology of the auditory system, and breast and lung cancers.
alphaO-conotoxin GeXIVA is a potent antagonist of rat alpha9alpha10 nAChRs, with
the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible
isomers. In the rat chronic constriction injury model of neuropathic pain, this
isomer reduced mechanical hyperalgesia without affecting motor performance. Here,
we report the effects of the three disulfide bond isomers of GeXIVA on human
alpha9alpha10 nAChRs, other human nAChR subtypes, various rat nAChR subtypes, and
10 rat alpha9alpha10 nAChR mutants. The three isomers displayed only ~5-fold
difference in potency on the human vs rat alpha9alpha10 receptors and had similar
affinities at wild-type rat alpha9alpha10 nAChRs and all 10 alpha9alpha10
receptor mutants. From these findings, the binding site and mechanism of action
of GeXIVA on rat and human alpha9alpha10 nAChR was deduced to be different from
that of other conotoxins targeting this nAChR subtype. GeXIVA is therefore a
unique ligand that might prove useful for further probing of binding sites on the
alpha9alpha10 nAChR. This article is part of the Special Issue entitled 'Venom
derived Peptides as Pharmacological Tools.'
PMID- 28416447
TI - Evolutionary Origins of cGAS-STING Signaling.
AB - Detection of foreign nucleic acids is an important strategy for innate immune
recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the
cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger
cGAMP to activate the signaling adaptor STING. While induction of antiviral type
I interferons (IFNs) is the major outcome of STING activation in vertebrates, it
has recently become clear that core components of the cGAS-STING pathway evolved
more than 600 million years ago, predating the evolution of type I IFNs. Here we
discuss the evolutionary origins of the cGAS-STING pathway, and consider the
possibility that the ancestral functions of STING may have included activation of
antibacterial immunity.
PMID- 28416446
TI - Patterns, Receptors, and Signals: Regulation of Phagosome Maturation.
AB - Recognition of microbial pathogens and dead cells and their phagocytic uptake by
specialized immune cells are essential to maintain host homeostasis. Phagosomes
undergo fusion and fission events with endosomal and lysosomal compartments, a
process called 'phagosome maturation', which leads to the degradation of the
phagosomal content. However, many phagocytic cells also act as antigen-presenting
cells and must balance degradation and peptide preservation. Emerging evidence
indicates that receptor engagement by phagosomal cargo, as well as inflammatory
mediators and cellular activation affect many aspects of phagosome maturation.
Unsurprisingly, pathogens have developed strategies to hijack this machinery,
thereby interfering with host immunity. Here, we highlight progress in this
field, summarize findings on the impact of immune signals, and discuss
consequences for pathogen elimination.
PMID- 28416448
TI - Immunological Memory of Group 2 Innate Lymphoid Cells.
AB - Immunological memory has long been described as a property of the adaptive immune
system that results in potent responses on exposure to an antigen encountered
previously. While this definition appears to exclude cells that do not express
antigen receptors, recent studies have shown that innate immune cells, including
natural killer (NK) cells, macrophages, and, more recently, group 2 innate
lymphoid cells (ILC2s) can record previous activations and respond more
vigorously on reactivation. Here we review the similarities and differences
between these forms of memory and the underlying mechanisms. Based on these
insights, we propose to revise the definition of immunological memory, as the
capacity to remember being previously activated and respond more efficiently on
reactivation regardless of antigen specificity.
PMID- 28416449
TI - Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence
Based Discovery.
AB - Complement dysregulation underlies several inflammatory disorders, and terminal
complement inhibition has thus far afforded significant clinical gains.
Nonetheless, emerging pathologies, fueled by complement imbalance and therapy
skewing genetic variance, underscore the need for more comprehensive, disease
tailored interventions. Modulation at the level of C3, a multifaceted
orchestrator of the complement cascade, opens up prospects for broader
therapeutic efficacy by targeting multiple pathogenic pathways modulated by C3
triggered proinflammatory crosstalk. Notably, C3 intervention is emerging as a
viable therapeutic strategy for renal disorders with predominantly complement
driven etiology, such as C3 glomerulopathy (C3G). Using C3G as a paradigm, we
argue that concerns about the feasibility of long-term C3 intervention need to be
placed into perspective and weighed against actual therapeutic outcomes in
prospective clinical trials.
PMID- 28416450
TI - Denoise diffusion-weighted images using higher-order singular value
decomposition.
AB - Noise usually affects the reliability of quantitative analysis in diffusion
weighted (DW) magnetic resonance imaging (MRI), especially at high b-values
and/or high spatial resolution. Higher-order singular value decomposition (HOSVD)
has recently emerged as a simple, effective, and adaptive transform to exploit
sparseness within multidimensional data. In particular, the patch-based HOSVD
denoising has demonstrated superb performance when applied to T1-, T2-, and
proton density-weighted MRI data. In this study, we aim to investigate the
feasibility of denoising DW data using the HOSVD transform. With the low signal
to-noise ratio in typical DW data, the patch-based HOSVD denoising suffers from
stripe artifacts in homogeneous regions because of the HOSVD bases learned from
the noisy patches. To address this problem, we propose a novel denoising method.
It first introduces a global HOSVD-based denoising as a prefiltering stage to
guide the subsequent patch-based HOSVD denoising stage. The HOSVD bases from the
patch groups in prefiltered images are then used to transform the noisy patch
groups in original DW data. Experiments were performed using simulated and in
vivo DW data. Results show that the proposed method significantly reduces stripe
artifacts compared with conventional patch-based HOSVD denoising methods, and
outperforms two state-of-the-art denoising methods in terms of denoising quality
and diffusion parameters estimation.
PMID- 28416451
TI - Diffeomorphic functional brain surface alignment: Functional demons.
AB - Aligning brain structures across individuals is a central prerequisite for
comparative neuroimaging studies. Typically, registration approaches assume a
strong association between the features used for alignment, such as macro
anatomy, and the variable observed, such as functional activation or
connectivity. Here, we propose to use the structure of intrinsic resting state
fMRI signal correlation patterns as a basis for alignment of the cortex in
functional studies. Rather than assuming the spatial correspondence of functional
structures between subjects, we have identified locations with similar
connectivity profiles across subjects. We mapped functional connectivity
relationships within the brain into an embedding space, and aligned the resulting
maps of multiple subjects. We then performed a diffeomorphic alignment of the
cortical surfaces, driven by the corresponding features in the joint embedding
space. Results show that functional alignment based on resting state fMRI
identifies functionally homologous regions across individuals with higher
accuracy than alignment based on the spatial correspondence of anatomy. Further,
functional alignment enables measurement of the strength of the anatomo
functional link across the cortex, and reveals the uneven distribution of this
link. Stronger anatomo-functional dissociation was found in higher association
areas compared to primary sensory- and motor areas. Functional alignment based on
resting state features improves group analysis of task based functional MRI data,
increasing statistical power and improving the delineation of task-specific core
regions. Finally, a comparison of the anatomo-functional dissociation between
cohorts is demonstrated with a group of left and right handed subjects.
PMID- 28416452
TI - Associated motivational salience impacts early sensory processing of human faces.
AB - Facial expressions of emotion have an undeniable processing advantage over
neutral faces, discernible both at behavioral level and in emotion-related
modulations of several event-related potentials (ERPs). Recently it was proposed
that also inherently neutral stimuli might gain salience through associative
learning mechanisms. The present study investigated whether acquired motivational
salience leads to processing advantages similar to biologically determined
origins of inherent emotional salience by applying an associative learning
paradigm to human face processing. Participants (N=24) were trained to categorize
neutral faces to salience categories by receiving different monetary outcomes.
ERPs were recorded in a subsequent test phase consisting of gender decisions on
previously associated faces, as well as on familiarized and novel faces
expressing happy, angry or no emotion. Previously reward-associated faces boosted
the P1 component, indicating that acquired reward-associations modulate early
sensory processing in extrastriate visual cortex. However, ERP modulations to
emotional - primarily angry - expressions expanded to subsequent processing
stages, as reflected in well-established emotion-related ERPs. The present study
offers new evidence that motivational salience associated to inherently neutral
stimuli can sharpen sensory encoding but does not obligatorily lead to
preferential processing at later stages.
PMID- 28416453
TI - High resolution data analysis strategies for mesoscale human functional MRI at 7
and 9.4T.
AB - The advent of ultra-high field functional magnetic resonance imaging (fMRI) has
greatly facilitated submillimeter resolution acquisitions (voxel volume below
(1mm3)), allowing the investigation of cortical columns and cortical depth
dependent (i.e. laminar) structures in the human brain. Advanced data analysis
techniques are essential to exploit the information in high resolution functional
measures. In this article, we use recent, exemplary 9.4T human functional and
anatomical data to review the advantages and disadvantages of (1) pooling high
resolution data across regions of interest for cortical depth profile analysis,
(2) pooling across cortical depths for mapping patches of cortex while discarding
depth-dependent (i.e. columnar) effects, and (3) isotropic sampling without
pooling to assess individual voxel's responses. A set of cortical depth meshes
may be a solution to sampling information tangentially while keeping
correspondence across depths. For quantitative analysis of the spatial
organization in fine-grained structures, a cortical grid approach is
advantageous. We further extend this general framework by combining it with a
previously introduced cortical layer volume-preserving (equi-volume) approach.
This framework can readily accommodate the research questions which allow for
spatial smoothing within or across layers. We demonstrate and discuss that equi
volume sampling yields a slight advantage over equidistant sampling given the
current limitations of fMRI voxel size, participant motion, coregistration and
segmentation. Our 9.4T human anatomical and functional data indicate the
advantage over lower fields including 7T and demonstrate the practical
applicability of T2* and T2-weighted fMRI acquisitions.
PMID- 28416454
TI - E1a is an exogenous in vivo tumour suppressor.
AB - The E1a gene from adenovirus has become a major tool in cancer research. Since
the discovery of E1a, it has been proposed to be an oncogene, becoming a key
element in the model of cooperation between oncogenes. However, E1a's in vivo
behaviour is consistent with a tumour suppressor gene, due to the block/delay
observed in different xenograft models. To clarify this interesting controversy,
we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo.
Initially, a conventional xenograft approach was performed using previously
unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect
regardless of the mouse's immunological background
(immunosuppressed/immunocompetent). Next, we engineered a transgenic mouse model
in which inducible E1a 13s expression was under the control of cytokeratin 5 to
avoid side effects during embryonic development. Our results show that E1a is
able to block chemical skin carcinogenesis, showing an anti-tumour effect. The
present report demonstrates the in vivo anti-tumour effect of E1a, showing that
the in vitro oncogenic role of E1a cannot be extrapolated in vivo, supporting its
future use in gene therapy approaches.
PMID- 28416455
TI - Protection from Cr(VI)-induced malignant cell transformation and tumorigenesis of
Cr(VI)-transformed cells by luteolin through Nrf2 signaling.
AB - Cr(VI) is a well known environmental carcinogen, but its mechanism of action and
the measures required to mitigate its effects remain to be investigated. Our
previous studies showed that exposure of human bronchial epithelial (BEAS-2B)
cells to Cr(VI) caused malignant transformation, that these transformed cells
progressed through tumorigenesis, and that luteolin, a natural compound,
inhibited both of these processes. The present study investigates the underlying
mechanisms by which luteolin protects cells against Cr(VI)-induced transformation
and tumorigenesis. The present study shows that luteolin activates inducible Nrf2
to inhibit Cr(VI)-generated reactive oxygen species (ROS) in normal BEAS-2B
cells. The decreased ROS level is likely responsible for the protective effect of
luteolin against Cr(VI)-induced malignant cell transformation in normal cells. By
contrast, in cells that have been transformed by Cr(VI), Nrf2 is constitutively
activated, and its target proteins, heme oxygenase 1 (HO-1), NAD(P)H:quinone
oxidoreductase 1 (NQO1), and superoxide dismutase 1/2 (SOD1/SOD2) are all
constitutively activated, and ROS levels are low. Bcl-2, an anti-apoptotic
protein and target protein of Nrf2 is elevated. Cr(VI)-transformed BEAS-2B cells
develop apoptosis resistance, increasing the survival of these transformed cells.
Luteolin decreases interactions between Nrf2 and the antioxidant response element
sites of its target anti-apoptotic and antioxidant proteins, Bcl-2, Bcl-XL, and
HO-1, which results in decreased constitutive Nrf2 activation. The decreased
constitutive Nrf2 activation, decrease in Nrf2 target proteins and consequent
apoptosis resistance by luteolin are possible mechanisms that mediate the
protective effect of luteolin in Cr(VI)-transformed cells.
PMID- 28416456
TI - Licoricidin inhibits the growth of SW480 human colorectal adenocarcinoma cells in
vitro and in vivo by inducing cycle arrest, apoptosis and autophagy.
AB - Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer
activities, but the active ingredients and underlying mechanisms have not been
revealed. By screening the cytotoxic activities of 122 licorice compounds against
SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD)
inhibited SW480 cell viability with an IC50 value of 7.2MUM. Further studies
indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in
SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation
of caspase-dependent pro-apoptotic signaling. Meanwhile, LCD promoted autophagy
in SW480 cells, and activated AMPK signaling and inhibited Akt/mTOR pathway.
Overexpression of a dominant-negative AMPKalpha2 abolished LCD-induced inhibition
of Akt/mTOR, autophagic and pro-apoptotic signaling pathways, and significantly
reversed loss of cell viability, suggesting activation of AMPK is essential for
the anti-cancer activity of LCD. In vivo anti-tumor experiments indicated that
LCD (20mg/kg, i.p.) significantly inhibited the growth of SW480 xenografts in
nude mice with an inhibitory rate of 43.5%. In addition, we obtained the
glycosylated product LCDG by microbial transformation, and found that
glycosylation slightly enhanced the in vivo anti-cancer activities of LCD. This
study indicates that LCD could inhibit SW480 cells by inducing cycle arrest,
apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic
agent against colorectal cancer.
PMID- 28416457
TI - Mono-2-ethylhexyl phthalate inhibits human extravillous trophoblast invasion via
the PPARgamma pathway.
AB - Concerns over the adverse reproductive outcomes in human have been raised, more
evidence including the underlying mechanism are required. Since extravillous
trophoblast (EVT) invasion is an important physiological step during early
development, the effects of mono-2-ethylhexyl phthalate (MEHP), the bioactive
metabolite of DEHP, on EVT invasion were investigated using Matrigel-coated
transwell chambers and cell line HTR-8/SVneo. In the transwell-based invasive
assay, MEHP exposure inhibited EVT invasion as judged by decreased invasion
index. Further analysis showed that MEHP exposure significantly inhibited the
activity of matrix metalloproteinase-9 (MMP-9), which is an important positive
regulator of EVT invasion. Meanwhile, the protein levels of tissue inhibitor
matrix metalloproteinase-1 (TIMP-1), one key negative regulator of EVT invasion,
were upregulated by MEHP treatment. Finally, inactivation of PPARgamma pathway by
either PPARgamma inhibitors or PPARgamma shRNA knockdown rescued the MEHP-induced
inhibited invasion of HTR-8/SVneo cells, which is accompanied by the recovery of
inhibited MMP-9 expression. The present study provides the evidence that MEHP
exposure inhibits trophoblast invasion via PPARgamma at concentrations comparable
to those found in humans, which provides an insight in understanding the
mechanisms of DEHP-associated early pregnancy loss.
PMID- 28416458
TI - On the origins of sex-based differences in respiratory disorders: Lessons and
hypotheses from stress neuroendocrinology in developing rats.
AB - The environment plays a critical role in shaping development and function of the
brain. Stress, especially when experienced early in life, can interfere with
these processes. In the context of respiratory control, perinatal stress can
therefore alter the ability to achieve the "fine-tuning" necessary for proper
detection of chemosensory stimuli and production of an adequate motor
(respiratory) command. Depending on the timing, intensity, and duration, the
detrimental consequences of perinatal exposure to adverse conditions on the
respiratory network become manifest at various life stages and can persist into
adulthood. During early life, respiratory diseases commonly associated with
dysfunction of neural networks include apnea of prematurity (AOP) and cardio
respiratory failure leading to sudden infant death syndrome (SIDS). Sleep
disordered breathing (SDB) can occur at various life stages, including adulthood.
Regardless of age, a common element of these disorders is their greater
prevalence in males. While this sexual dimorphism points to a potential role of
sex hormones, our understanding of the neuroendocrine mechanisms remain poorly
understood. In addition to their modulatory influence on breathing, gonadal
hormones regulate sexual differentiation of the brain. Stress alters these
effects, and over the years our laboratory has used various perinatal stress
protocols to gain insight into the origins of sex-based differences in
respiratory disorders. This review discusses our recent advances with a focus on
the sex-specific impact of early life stress on O2-chemoreflex function both in
newborn and adult rats. We conclude by discussing the basic principles emerging
from this work, potential mechanisms, and clinical relevance.
PMID- 28416459
TI - The error of Broca: From the traditional localizationist concept to a connectomal
anatomy of human brain.
AB - Neurology, especially aphasiology, was mainly built on behavioral-structural
correlations ("lesion method"). In this setting, Broca's area has been considered
as the "speech area"; moreover, this observation led to localizationism. However,
advances in brain mapping techniques, as functional neuroimaging and direct
electrical stimulation in patients undergoing awake surgery for gliomas, has
resulted in a paradigmatic shift regarding models of neural architecture. In
fact, the brain is organized in distributed complex networks underpinning
sensorimotor, visuospatial, language, cognitive and emotional functions. In this
connectomal workframe, cerebral processing is not conceived as the sum of
segregated subfunctions, but results from the integration and potentiation of
parallel (even if partially overlapped) subcircuits. Such a networking model,
taking into account cortical and subcortical anatomic constraints, explains
interindividual variability in physiology and after brain damage, particularly in
aphasiology - e.g. double dissociations during electrostimulations, as
comprehension versus naming disorders, semantic versus phonemic paraphasias, or
syntactic disturbances versus anomia. This dynamic organization mediated by the
well-synchronized functioning of delocalized groups of interconnected neurons
(rather than by discrete centers) also explains the huge potential of
neuroplasticity following cerebral insult, on the condition that the axonal
connectivity is preserved. According to this principle, massive surgical
resection of brain regions dogmatically considered as "critical" in a
localisationist view can be achieved with no functional deficit, as the removal
of Broca's area - which is not the speech area - without disorders. This
connectomal account of neural processing may have major implications in cognitive
neurosciences and in therapeutic management of brain-damaged patients.
PMID- 28416460
TI - Regional distribution of cholinergic, catecholaminergic, serotonergic and
orexinergic neurons in the brain of two carnivore species: The feliform banded
mongoose (Mungos mungo) and the caniform domestic ferret (Mustela putorius furo).
AB - The nuclear organization of the cholinergic, catecholaminergic, serotonergic and
orexinergic neurons in the brains of two species of carnivore, the banded
mongoose (Mungos mungo) and domestic ferret (Mustela putorius furo), is
presented. The banded mongoose belongs to the feliform suborder and the domestic
ferret to the caniform suborder, having last shared a common ancestor
approximately 53 million years ago; however, they have a very similar overall
morphology and life history, presenting an interesting opportunity to examine the
extent of evolutionary plasticity in these systems. The brains of the two
carnivore species were coronally sectioned and immunohistochemically stained with
antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and
orexin-A. The overall organization and complement of the nuclei of these systems
was identical between the two species, although minor differences were noted.
Moreover, this overall organization is identical to other studies undertaken in
the domestic cat and dog. While for the most part the nuclei forming these
systems are similar to those observed in other mammals, two species differences,
which appear to be carnivore-specific, were noted. First, cholinergic neurons
were observed in the lateral septal nucleus of both species, an apparently
carnivore specific feature not recorded previously in other mammals. Second, the
serotonergic neurons of the peripheral division of the dorsal raphe complex
exhibited a significant caudad expansion, intermingling with the cholinergic and
catecholaminergic nuclei of the pons, a carnivore specific feature. These
carnivore specific features likely have functional consequences related to coping
with stress and the expression of sleep.
PMID- 28416462
TI - Clinical assessment of 115 cases of hindfoot fusion with two different types of
graft: Allograft+DBM+bone marrow aspirate versus autograft+DBM.
AB - INTRODUCTION: Nonunion is a common complication (15%) of hindfoot and ankle
arthrodesis. Autograft can improve the fusion rate because of its
osteoconductive, osteoinductive and osteogenic properties. However, autograft
harvesting is a source of morbidity. One alternative is to combine allograft with
demineralized bone matrix (DBM) and iliac bone marrow aspirate (BMA). This
combination graft has similar biological properties to healthy bone. When used
alone, allograft has osteoconductive and sometimes structural properties. DBM
provides osteoinduction and improves the osteconductivity. BMA adds cells and
thereby osteogenic potential. HYPOTHESIS: Given its intrinsic properties,
allograft-DBM-BMA is as effective as autograft-DBM treatment while simplifying
the clinical practice. MATERIAL AND METHODS: One hundred and fifteen cases of
ankle and hindfoot arthrodesis were studied in 82 patients divided in two groups:
autograft-DBM vs allograft-DBM-BMA. Treatment effectiveness was assessed using
clinical (time to fusion, fusion rate) and radiological (trabecular bone bridge,
disappearance of joint space) criteria. A CT scan was done in 60% of cases when
fusion could not be confirmed using the clinical and radiological criteria.
RESULTS: There was no significant difference between the two groups in terms of
fusion rate, time to fusion, number of heterotopic ossifications, revision rate
and quantity of DBM used. The nonunion rate was 18% in the autograft group and
13% in the allograft group. The infection rate was 11% in the autograft and 4% in
the allograft group. DISCUSSION: Allograft-DBM-BMA is an alternative to autograft
DBM that provides similar effectiveness without increasing the number of nonunion
or complications. Osteonecrosis and surgical revision are risk factors. LEVEL OF
EVIDENCE: III retrospective study.
PMID- 28416461
TI - Detection of penetration of the dorsal cortex by epiphyseal screws of distal
radius volar plates: Anatomical study comparing ultrasound and fluoroscopy.
AB - HYPOTHESIS: Osteosynthesis of the distal radius by a volar plate can be
complicated by lesions of extensor tendons by screws penetrating the dorsal
cortex. The fluoroscopic skyline view enables to confirm the length of the
screws. To avoid its risk of irradiation, some authors have recommended using
ultrasound instead. MATERIAL AND METHODS: The goal of this study was to
demonstrate that the detection rate of screws penetrating the dorsal cortex was
at least as good using ultrasound compared to fluoroscopic skyline. A volar plate
in which one screw penetrated the dorsal cortex was implanted in 10 cadaveric
wrists. Three observers had to detect which screw penetrated the dorsal cortex
using ultrasound and then a fluoroscopic skyline. RESULTS: The detection rate of
screws penetrating the dorsal cortex was 43.33% with ultrasound and 96.97% using
the fluoroscopic skyline. Agreement between the observers was poor with
ultrasound and good with fluoroscopy. CONCLUSION: Our results show that
ultrasound cannot replace the fluoroscopic skyline view to detect screws
penetrating the dorsal cortex of the distal radius in clinical practice. LEVEL OF
EVIDENCE: II.
PMID- 28416463
TI - Glucocorticoids activate a synapse weakening pathway culminating in tau
phosphorylation in the hippocampus.
AB - Evidence suggests that the stress hormones glucocorticoids (GCs) can cause
cognitive deficits and neurodegeneration. Previous studies have found GCs
facilitate physiological synapse weakening, termed long-term depression (LTD),
though the precise mechanisms underlying this are poorly understood. Here we show
that GCs activate glycogen synthase kinase-3 (GSK-3), a kinase crucial to synapse
weakening signals. Critically, this ultimately leads to phosphorylation of the
microtubule associated protein tau, specifically at the serine 396 residue, and
this is a causal factor in the GC-mediated impairment of synaptic function. These
findings reveal the link between GCs and synapse weakening signals, and the
potential for stress-induced priming of neurodegeneration. This could have
important implications for our understanding of how stress can lead to
neurodegenerative disease.
PMID- 28416464
TI - Microbiological quality of water in a city with persistent and recurrent
waterborne diseases under tropical sub-rural conditions: The case of Kikwit City,
Democratic Republic of the Congo.
AB - The availability of safe drinking water in sub-Saharan countries remains a major
challenge because poor sanitation has been the cause of various outbreaks of
waterborne disease due to the poor microbiological quality of water used for
domestic purposes. The faecal indicator bacteria (FIB) used in the present study
included Escherichia coli (E. coli) and Enterococcus (ENT). FIB and aerobic
mesophilic bacteria (AMB) were quantified during July 2015 (dry season) and
November 2015 (rainy season) in order to assess the quality of drinking water
from wells (n=3; P1-P3), and two rivers, the River Lukemi (RLK, n=3) and River
Luini (RLN, n=2) in the city of Kikwit, which is located in the province of Kwilu
in the Democratic Republic of the Congo. Kikwit is well known for its outbreaks
of persistent and recurrent waterborne diseases including Entamoeba, Shigella,
typhoid fever, cholera, and Ebola Viral Hemorrhagic Fever. Consequently, E. coli,
ENT, and AMB were quantified in water samples according to the standard
international methods for water quality determination using the membrane
filtration method. The FIB characterization was performed for human-specific
Bacteroides by PCR using specific primers. The results obtained revealed high FIB
concentrations in river samples collected during both seasons. For example, E.
coli respectively reached 4.3*104 and 9.2*104 CFU 100mL-1 in the dry season and
the wet season. ENT reached 5.3*103 CFU 100mL-1 during the dry season and 9.8*103
CFU 100mL-1 in the wet season. The pollution was significantly worse in the wet
season compared to the dry season. Surprisingly, no faecal contamination was
observed in well water samples collected in the dry season while E. coli and ENT
were detected in all wells in the wet season with values of 6, 7, and 11CFUmL-1
for E. coli in wells P1-P3, respectively and 3, 5, 9 CFU mL-1for ENT in the same
wells. Interestingly, the PCR assays for human-specific Bacteroides HF183/HF134
indicated that 97-100% captured in all analyses of isolated FIB were of human
origin. The results indicate that contamination of E. coli, ENT, and AMB in the
studied water resources increases during the wet season. This study improves
understanding of the microbiological pollution of rivers and wells under tropical
conditions and will guide future municipal/local government decisions on
improving water quality in this region which is characterised by persistent and
recurrent waterborne diseases. Although the epidemiology can be geographically
localised, the effects of cross border transmission can be global. Therefore, the
research results presented in this article form recommendations to
municipalities/local authorities and the approach and procedures can be carried
out in a similar environment.
PMID- 28416465
TI - 15 years of monitoring occupational exposure to respirable dust and quartz within
the European industrial minerals sector.
AB - INTRODUCTION: In 2000, a prospective Dust Monitoring Program (DMP) was started in
which measurements of worker's exposure to respirable dust and quartz are
collected in member companies from the European Industrial Minerals Association
(IMA-Europe). After 15 years, the resulting IMA-DMP database allows a detailed
overview of exposure levels of respirable dust and quartz over time within this
industrial sector. Our aim is to describe the IMA-DMP and the current state of
the corresponding database which due to continuation of the IMA-DMP is still
growing. The future use of the database will also be highlighted including its
utility for the industrial minerals producing sector. METHODS: Exposure data are
being obtained following a common protocol including a standardized sampling
strategy, standardized sampling and analytical methods and a data management
system. Following strict quality control procedures, exposure data are
consequently added to a central database. The data comprises personal exposure
measurements including auxiliary information on work and other conditions during
sampling. RESULTS: Currently, the IMA-DMP database consists of almost 28,000
personal measurements which have been performed from 2000 until 2015 representing
29 half-yearly sampling campaigns. The exposure data have been collected from 160
different worksites owned by 35 industrial mineral companies and comes from 23
European countries and approximately 5000 workers. CONCLUSION: The IMA-DMP
database provides the European minerals sector with reliable data regarding
worker personal exposures to respirable dust and quartz. The database can be used
as a powerful tool to address outstanding scientific issues on long-term exposure
trends and exposure variability, and importantly, as a surveillance tool to
evaluate exposure control measures. The database will be valuable for future
epidemiological studies on respiratory health effects and will allow for
estimation of quantitative exposure response relationships.
PMID- 28416466
TI - Risk of atrioesophageal fistula formation with contact force-sensing catheters.
AB - BACKGROUND: Atrioesophageal fistula formation is a rare but life-threatening
complication of atrial fibrillation ablation. Contact force (CF)-sensing
catheters improve procedural effectiveness. However, the impact of the
implementation of CF-sensing technology on the risk of atrioesophageal fistula
formation has not been explored. OBJECTIVE: The purpose of this study was to
determine the association between the use of CF-sensing catheters and
atrioesophageal fistula development. METHODS: We searched the Manufacturer and
User Facility Device Experience database for adverse event reports involving Food
and Drug Administration-approved ablation catheters. RESULTS: Among 2689 device
reports, we identified 78 atrioesophageal fistula cases, 65 of which involved CF
sensing catheters and 13 non-CF-sensing catheters. The percentage of total
reports involving atrioeosphageal fistula was 5.4% for CF-sensing catheters (65
of 1202) and 0.9% for non-CF-sensing catheters (13 of 1487) (P < .0001).
Procedural details (CF and power settings) were not consistently reported.
Esophageal temperature increases were detected in only 2.5% of cases (2 of 78).
The mean time to presentation was 16 +/- 9 days. Overall mortality was at least
56%, with patients who underwent surgical repair more likely to survive than
those treated with stenting or no intervention. CONCLUSION: Atrioesophageal
fistula formation accounted for a much higher proportion of reported adverse
events with CF-sensing catheters compared with non-CF-sensing catheters. Improved
understanding of the relationship between power/force delivery and esophageal
damage is needed to minimize the risk of atrioesophageal fistula formation.
PMID- 28416467
TI - Early repolarization is associated with a significantly increased risk of
ventricular arrhythmias and sudden cardiac death in patients with structural
heart diseases.
AB - BACKGROUND: Early repolarization pattern (ERP) has been proved to increase risk
of arrhythmia death in the general population, but its prognostic significance in
patients with structural heart disease (SHD) is controversial. OBJECTIVE: The
purpose of this study was to conduct a meta-analysis of studies assessing the
association between ERP and risk of ventricular arrhythmias (VTAs) and sudden
cardiac death (SCD) in patients with SHD. METHODS: We performed a literature
search using MEDLINE (January 1, 1966, to September 25, 2016) and EMBASE (January
1, 1980, to September 25, 2016) with no restrictions. Studies that reported odds
ratio (OR) estimates with 95% confidence intervals (CIs) for the associations of
interest were included. RESULTS: The search yielded 19 observational studies,
involving 7268 patients that reported 1127 cases of VTAs or SCD. In the selected
studies, the point estimates of the ORs were consistently greater than 1.
Compared with those without ERP, patients with ERP experienced a significantly
increased risk of developing VTAs or SCD (OR 4.76; 95% CI 3.62-6.26), ventricular
fibrillation (OR 7.14; 95% CI 4.31-11.82), and SCD (OR 4.07; 95% CI 1.58-10.51).
The results were consistent and statistically significant in all subgroups. ERP
with J-point elevation in inferior leads, notching configuration, and horizontal
or descending ST segment connote higher risk. CONCLUSION: ERP is associated with
a significant increased risk of VTAs or SCD in patients with SHD. Future research
should attempt to understand the exact mechanisms for the arrhythmia risk and to
introduce ERP in the risk stratification in this patient group.
PMID- 28416468
TI - Cardiac transplantation in children and adolescents with long QT syndrome.
AB - BACKGROUND: Long QT syndrome (LQTS) is a potentially lethal, yet highly
treatable, cardiac channelopathy. Cardiac transplantation has been reported
anecdotally for patients with severe LQTS refractory to standard therapies.
OBJECTIVE: The purpose of this study was to evaluate the incidence of and risk
factors for cardiac transplantation in children evaluated and treated in an LQTS
specialty center. METHODS: This was a retrospective review of 349 children with
LQTS (mean age at diagnosis, 8.0 +/- 5.7 years; mean corrected QT interval, 469
+/- 51 ms; long QT syndrome type 1 [LQT1] in 46%, LQT2 in 31%, and LQT3 in 9%)
evaluated from 2000 to 2013. A subset analysis was performed on patients referred
for cardiac transplantation. RESULTS: Only 3 patients (0.9%; all LQT3; 2 female)
underwent cardiac transplantation at ages 4, 11, and 17 years. Overall, 90 of 349
(26%) were symptomatic (exhibited LQTS-associated cardiac events) before LQTS
diagnosis, including those who ultimately underwent transplant. Age at sentinel
event was associated with transplantation (3 of 26 [12%] with an event at <1 year
of life were transplanted vs 0 of 64 with an event after age 1; P = .02).
Genotype was also a risk factor (3 of 32 patients with LQT3 were transplanted
[9.4%] vs 0 of 270 patients with LQT1 or LQT2; P = .001). Before transplant, all
patients had recurrent ventricular fibrillation-terminating shocks despite
combination drug therapy and bilateral sympathetic denervation. All transplanted
patients are alive at follow-up. CONCLUSION: Cardiac transplantation is seldom
necessary for the management of LQTS. However, patients with LQT3 and in
utero/neonatal expressivity are at higher risk of treatment failure and
refractory ventricular arrhythmias with standard therapy, and cardiac
transplantation should be considered for this malignant subset of LQTS.
PMID- 28416470
TI - Block ionomer micellar nanoparticles from double hydrophilic copolymers,
classifications and promises for delivery of cancer chemotherapeutics.
AB - A class of double hydrophilic copolymers comprising ionic and nonionic water
soluble blocks, which are also called block ionomers, represent an interesting
type of polymer assembly forming stable, homogeneous core-corona dispersions.
They exhibit the solution behavior of normal polyelectrolytes, whereas assembly
into micelle, vesicle or disk morphology happens by an external stimulus (pH,
temperature or ionic strength) or complex formation with metal ions, ionic
surfactants, polyelectrolytes, etc. Temperature, pH, redox or salt sensitivity
affords a unique opportunity to control the triggered release of payloads
accommodated through electrostatic interaction, coordination or chemical
conjugation. Moreover, the non-ionic block provides the surface passivation,
prolongation of the blood circulation and tumor accumulation, supporting targeted
delivery of chemotherapeutic agents based on pathophysiology of tumor
microenvironment. Potentiation of antitumor activity, sensitization of the
resistant tumors, increased tolerated dose and translation into clinical practice
are among their most intriguing characteristics. Their high functionality has
been suggested for co-delivery of multiple agents for reversal of chemo
resistance as well as simultaneous therapy and diagnostics. Nevertheless, some
stability concerns may be raised due to the polymer disassembly beyond a critical
concentration of pH, salt and polyion concentration that can be modulated by
introducing crosslinks between the polymer chains (Nano-networks).
PMID- 28416472
TI - Oesophageal cancer presenting as Lemierre's syndrome caused by Streptococcus
anginosus.
AB - A 59-year-old man presented to the emergency department with complaints of
dysphagia, right-sided neck swelling, fever and chills. Physical examination was
remarkable for fever and tender swelling over the right side of the neck.
Laboratory investigations revealed leucocytosis with neutrophilia. CT of the neck
showed right internal jugular vein thrombosis with an overlying abscess and a
nodular opacity in the right lung apex with air locules. He underwent surgical
drainage of the neck abscess. Aerobic cultures from the drainage and blood
cultures grew Streptococcus anginosus Given his initial complaint of dysphagia,
upper endoscopy was performed which showed a mass in the upper oesophagus.
Histopathology confirmed squamous cell carcinoma. The patient received 6 weeks of
antibiotics therapy.
PMID- 28416473
TI - Ollier's disease: features of the hands.
PMID- 28416474
TI - Posterior reversible encephalopathy in an adult patient with poststreptococcal
glomerulonephritis.
PMID- 28416471
TI - Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for
Leukemic Stem Cells but Require Oxidative Metabolism.
AB - Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be
enriched in quiescent immature leukemic stem cells (LSC). To validate this
hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach
treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual
AML cells are enriched in neither immature, quiescent cells nor LSCs. Strikingly,
AraC-resistant preexisting and persisting cells displayed high levels of reactive
oxygen species, showed increased mitochondrial mass, and retained active
polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS)
status. AraC residual cells exhibited increased fatty-acid oxidation, upregulated
CD36 expression, and a high OXPHOS gene signature predictive for treatment
response in PDX and patients with AML. High OXPHOS but not low OXPHOS human AML
cell lines were chemoresistant in vivo. Targeting mitochondrial protein
synthesis, electron transfer, or fatty-acid oxidation induced an energetic shift
toward low OXPHOS and markedly enhanced antileukemic effects of AraC. Together,
this study demonstrates that essential mitochondrial functions contribute to AraC
resistance in AML and are a robust hallmark of AraC sensitivity and a promising
therapeutic avenue to treat AML residual disease.Significance: AraC-resistant AML
cells exhibit metabolic features and gene signatures consistent with a high
OXPHOS status. In these cells, targeting mitochondrial metabolism through the
CD36-FAO-OXPHOS axis induces an energetic shift toward low OXPHOS and strongly
enhanced antileukemic effects of AraC, offering a promising avenue to design new
therapeutic strategies and fight AraC resistance in AML. Cancer Discov; 7(7); 716
35. (c)2017 AACR.See related commentary by Schimmer, p. 670This article is
highlighted in the In This Issue feature, p. 653.
PMID- 28416475
TI - Use of Canagliflozin in Kidney Transplant Recipients for the Treatment of Type 2
Diabetes: A Case Series.
PMID- 28416477
TI - Actin filament assembly by bacterial factors VopL/F: Which end is up?
AB - Competing models have been proposed for actin filament nucleation by the
bacterial proteins VopL/F. In this issue, Burke et al. (2017. J. Cell Biol.
https://doi.org/10.1083/jcb.201608104) use direct observation to demonstrate that
VopL/F bind the barbed and pointed ends of actin filaments but only nucleate new
filaments from the pointed end.
PMID- 28416478
TI - Stardust, the Janus-faced partner of Crumbs.
AB - The Drosophila melanogaster scaffolding protein Stardust (Sdt) stabilizes the
transmembrane protein Crumbs, a conserved regulator of apical-basal epithelial
polarity. In this issue, Perez-Mockus et al. (2017. J. Cell Biol
https://doi.org/10.1083/jcb.201611196) report that a subset of Sdt isoforms are
targeted by the ubiquitin ligase Neuralized, thus fine tuning the endocytosis and
activity of this apical determinant.
PMID- 28416480
TI - Correction to: Atypical presentation of a spontaneous celiac artery dissection
resulting in jejuna ischaemia.
PMID- 28416479
TI - Suppression of integrin alpha3beta1 by alpha9beta1 in the epidermis controls the
paracrine resolution of wound angiogenesis.
AB - Development of wound therapies is hindered by poor understanding of combinatorial
integrin function in the epidermis. In this study, we generated mice with
epidermis-specific deletion of alpha3beta1, alpha9beta1, or both integrins as
well as keratinocyte lines expressing these integrin combinations. Consistent
with proangiogenic roles for alpha3beta1, alpha3-null keratinocytes showed
reduced paracrine stimulation of endothelial cell migration and survival, and
wounds of epidermis-specific alpha3 knockout mice displayed impaired
angiogenesis. Interestingly, alpha9beta1 in keratinocytes suppressed alpha3beta1
mediated stimulation of endothelial cells, and wounds of epidermis-specific
alpha9 knockout mice displayed delayed vascular normalization and reduced
endothelial apoptosis, indicating that alpha9beta1 cross-suppresses alpha3beta1
proangiogenic functions. Moreover, alpha9beta1 inhibited alpha3beta1 signaling
downstream of focal adhesion kinase (FAK) autoactivation at the point of Src
mediated phosphorylation of FAK Y861/Y925. Finally, alpha9beta1 cross-suppressed
many alpha3beta1-dependent genes, including the gene that encodes MMP-9, which we
implicated as a regulator of integrin-dependent cross talk to endothelial cells.
Our findings identify a novel physiological context for combinatorial integrin
signaling, laying the foundation for therapeutic strategies that manipulate
alpha9beta1 and/or alpha3beta1 during wound healing.
PMID- 28416481
TI - Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and
Tumorigenesis in Colon.
AB - Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase
risks of colorectal cancer. Here, we performed a long-term diet study in mice to
follow tumorigenesis and characterize structural and metabolic changes in colon
mucosa associated with WD and predisposition to colorectal cancer. WD increased
colon tumor numbers, and mucosa proteomic analysis indicated severe deregulation
of intracellular bile acid (BA) homeostasis and activation of cell proliferation.
WD also increased crypt depth and colon cell proliferation. Despite increased
luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA
transporters FABP6, OSTbeta, and ASBT and decreased concentrations of secondary
BA deoxycholic acid and lithocholic acid, indicating reduced activity of the
nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer
risk by FXR inactivation, leading to BA deregulation and increased colon cell
proliferation. Cancer Res; 77(12); 3352-63. (c)2017 AACR.
PMID- 28416482
TI - NOTCH1 Signaling Regulates Self-Renewal and Platinum Chemoresistance of Cancer
Stem-like Cells in Human Non-Small Cell Lung Cancer.
AB - Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis,
relapse, and therapeutic resistance, but their specific pathogenic characters in
many cancers, including non-small cell lung cancer (NSCLC), have yet to be well
defined. Here, we develop findings that the growth factor HGF promotes CSC sphere
formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD
SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC).
In particular, we isolated a subpopulation of CD166+CD49fhiCD104-Lin- LCSC
present in all human specimens of NSCLC examined, regardless of their histologic
subtypes or genetic driver mutations. This specific cell population was
tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro
and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations
established that NOTCH1 was preferentially expressed in this cell subpopulation
and required for self-renewal via the transcription factor HES1. Through a
distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin
induced cell death. Notably, treatment with a gamma-secretase inhibitor that
blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum
sensitivity in vitro and in vivo Overall, our results define the pathogenic
characters of a cancer stem-like subpopulation in lung cancer, the targeting of
which may relieve platinum resistance in this disease. Cancer Res; 77(11); 3082
91. (c)2017 AACR.
PMID- 28416483
TI - SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug
Resistant Models of EGFR-Mutant Lung Cancer.
AB - Mutant-selective EGFR tyrosine kinase inhibitors (TKI), such as osimertinib, are
active agents for the treatment of EGFR-mutant lung cancer. Specifically, these
agents can overcome the effects of the T790M mutation, which mediates resistance
to first- and second-generation EGFR TKI, and recent clinical trials have
documented their efficacy in patients with EGFR-mutant lung cancer. Despite
promising results, therapeutic efficacy is limited by the development of acquired
resistance. Here we report that Src family kinases (SFK) and focal adhesion
kinase (FAK) sustain AKT and MAPK pathway signaling under continuous EGFR
inhibition in osimertinib-sensitive cells. Inhibiting either the MAPK pathway or
the AKT pathway enhanced the effects of osimertinib. Combined SFK/FAK inhibition
exhibited the most potent effects on growth inhibition, induction of apoptosis,
and delay of acquired resistance. SFK family member YES1 was amplified in
osimertinib-resistant EGFR-mutant tumor cells, the effects of which were overcome
by combined treatment with osimertinib and SFK inhibitors. In conclusion, our
data suggest that the concomitant inhibition of both SFK/FAK and EGFR may be a
promising therapeutic strategy for EGFR-mutant lung cancer. Cancer Res; 77(11);
2990-3000. (c)2017 AACR.
PMID- 28416484
TI - SSRP1 Cooperates with PARP and XRCC1 to Facilitate Single-Strand DNA Break Repair
by Chromatin Priming.
AB - DNA single-strand breaks (SSB) are the most common form of DNA damage, requiring
repair processes that to initiate must overcome chromatin barriers. The FACT
complex comprised of the SSRP1 and SPT16 proteins is important for maintaining
chromatin integrity, with SSRP1 acting as an histone H2A/H2B chaperone in
chromatin disassembly during DNA transcription, replication, and repair. In this
study, we show that SSRP1, but not SPT16, is critical for cell survival after
ionizing radiation or methyl methanesulfonate-induced single-strand DNA damage.
SSRP1 is recruited to SSB in a PARP-dependent manner and retained at DNA damage
sites by N-terminal interactions with the DNA repair protein XRCC1. Mutational
analyses showed how SSRP1 function is essential for chromatin decondensation and
histone H2B exchange at sites of DNA strand breaks, which are both critical to
prime chromatin for efficient SSB repair and cell survival. By establishing how
SSRP1 facilitates SSB repair, our findings provide a mechanistic rationale to
target SSRP1 as a general approach to selectively attack cancer cells. Cancer
Res; 77(10); 2674-85. (c)2017 AACR.
PMID- 28416486
TI - A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer.
AB - Nanotechnology offers many possibilities to improve drug treatments, including
with regard to drug pharmacology. The current study reports a simple approach to
improve cisplatin efficacy in the treatment of colon cancer through the creation
of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ
CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells
and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited
at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin,
reflecting an enhancement in intracellular accumulation and DNA platination.
Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production,
expression of heavy metal-inducible and stress-inducible genes, stress kinase
cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis,
oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and
azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue
toxicity. Our results offer preclinical validation of a nanocarrier formulation
that can safely improve chemotherapeutic efficacy, address risks of drug
resistance, and improve patient compliance by enabling oral administration.
Cancer Res; 77(11); 2964-75. (c)2017 AACR.
PMID- 28416485
TI - Targeting Autocrine CCL5-CCR5 Axis Reprograms Immunosuppressive Myeloid Cells and
Reinvigorates Antitumor Immunity.
AB - The tumor-promoting potential of CCL5 has been proposed but remains poorly
understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major
regulator of immunosuppressive myeloid cells (IMC) of both monocytic and
granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation
of granulocytic myeloid-derived suppressor cells and tumor-associated
macrophages. In parallel, enhanced maturation of intratumoral neutrophils and
macrophages occurred in spite of tumor-derived CCL5. The refractory nature of
ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their
persistent lack of membrane-bound CCR5. The changes in the ccl5-null myeloid
compartment subsequently resulted in increased tumor-infiltrating cytotoxic CD8+
T cells and decreased regulatory T cells in tumor-draining lymph nodes. An
analysis of human triple-negative breast cancer specimens demonstrated an inverse
correlation between "immune CCR5" levels and the maturation status of tumor
infiltrating neutrophils as well as 5-year-survival rates. Targeting the host
CCL5 in bone marrow via nanoparticle-delivered expression silencing, in
combination with the CCR5 inhibitor Maraviroc, resulted in strong reductions of
IMC and robust antitumor immunities. Our study suggests that the myeloid CCL5
CCR5 axis is an excellent target for cancer immunotherapy. Cancer Res; 77(11);
2857-68. (c)2017 AACR.
PMID- 28416487
TI - Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer
Aggressiveness by Ambient Ionization Mass Spectrometry Imaging.
AB - Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among
gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous
borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and
have relatively indolent clinical behavior. The underlying biological differences
between HGSC and BOT call for accurate diagnostic methodologies and tailored
treatment options, and identification of molecular markers of aggressiveness
could provide valuable biochemical insights and improve disease management. Here,
we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image
and chemically characterize the metabolic profiles of HGSC, BOT, and normal
ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine
papillary branches in serous BOT and allowed for characterization of spatial
features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC.
Predictive markers of cancer aggressiveness were identified, including various
free fatty acids, metabolites, and complex lipids such as ceramides,
glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification
models built from a total of 89,826 individual pixels, acquired in positive and
negative ion modes from 78 different tissue samples, enabled diagnosis and
prediction of HGSC and all tumor samples in comparison with normal tissues, with
overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination
was achieved with an overall accuracy of 93.0%. Interestingly, our classification
model allowed identification of three BOT samples presenting unusual histologic
features that could be associated with the development of low-grade carcinomas.
Our results suggest DESI-MS as a powerful approach for rapid serous ovarian
cancer diagnosis based on altered metabolic signatures. Cancer Res; 77(11); 2903
13. (c)2017 AACR.
PMID- 28416488
TI - Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor
Initiating Cells.
AB - Oncogenic signaling by NOTCH is elevated in brain tumor-initiating cells (BTIC)
in malignant glioma, but the mechanism of its activation is unknown. Here we
provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent
in malignant glioma, increases NOTCH activity in BTIC to promote their growth. We
demonstrate the proximal localization of TNC and BTIC in human glioblastoma
specimens and in orthotopic murine xenografts of human BTIC implanted
intracranially. In tissue culture, TNC was superior amongst several extracellular
matrix proteins in enhancing the sphere-forming capacity of glioma patient
derived BTIC. Exogenously applied or autocrine TNC increased BTIC growth through
an alpha2beta1 integrin-mediated mechanism that elevated NOTCH ligand Jagged1
(JAG1). Microarray analyses and confirmatory PCR and Western analyses in BTIC
determined that NOTCH signaling components including JAG1, ADAMTS15, and NICD1/2
were elevated in BITC after TNC exposure. Inhibition of gamma-secretase and
metalloproteinase proteolysis in the NOTCH pathway, or silencing of alpha2beta1
integrin or JAG1, reduced the proliferative effect of TNC on BTIC. Collectively,
our findings identified TNC as a pivotal initiator of elevated NOTCH signaling in
BTIC and define the establishment of a TN-alpha2beta1-JAG1-NOTCH signaling axis
as a candidate therapeutic target in glioma patients. Cancer Res; 77(12); 3231
43. (c)2017 AACR.
PMID- 28416489
TI - NRF2 Induction Supporting Breast Cancer Cell Survival Is Enabled by Oxidative
Stress-Induced DPP3-KEAP1 Interaction.
AB - NRF2 is a transcription factor serving as a master regulator of the expression of
many genes involved in cellular responses to oxidative and other stresses. In the
absence of stress, NRF2 is constantly synthesized but maintained at low levels as
it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation.
NRF2 binds KEAP1 mainly through a conserved "ETGE" motif that has also been found
in several other proteins, such as DPP3, which has been shown to bind KEAP1 and
enhance NRF2 function upon overexpression. Here we demonstrate the interaction
between endogenous DPP3 and endogenous KEAP1. We further show that the DPP3-KEAP1
interaction is strongly induced by hydrogen peroxide and that DPP3 is required
for timely NRF2 induction and nuclear accumulation in the estrogen receptor (ER)
positive MCF7 breast cancer cells. Moreover, we present evidence that the binding
of DPP3 to KEAP1 stabilizes the latter. Finally, we show that DPP3 is
overexpressed in breast cancer and that elevated levels of DPP3 mRNA correlate
with increased NRF2 downstream gene expression and poor prognosis, particularly
for ER-positive breast cancer. Our studies reveal novel insights into the
regulation of NRF2 and identify DPP3 and an NRF2 transcriptional signature as
potential biomarkers for breast cancer prognosis and treatment. Cancer Res;
77(11); 2881-92. (c)2017 AACR.
PMID- 28416490
TI - Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075
Suggests Combination Therapeutic Strategies.
AB - ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently
entered phase I clinical trials. Comprehensive preclinical characterization of
ABBV-075 demonstrated broad activity across cell lines and tumor models,
representing a variety of hematologic malignancies and solid tumor indications.
In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent
G1 cell-cycle arrest without extensive apoptosis. In this study, we show that
ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non
Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was
mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting
synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In
germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax
sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo
combination studies uncovered surprising benefits of low doses of ABBV-075
coupled with bortezomib and azacitidine treatment, despite the lack of in vitro
synergy between ABBV-075 and these agents. The in vitro/in vivo activities of
ABBV-075 described here may serve as a useful reference to guide the development
of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res;
77(11); 2976-89. (c)2017 AACR.
PMID- 28416491
TI - Locoregional Effects of Microbiota in a Preclinical Model of Colon
Carcinogenesis.
AB - Inflammation and microbiota are critical components of intestinal tumorigenesis.
To dissect how the microbiota contributes to tumor distribution, we generated
germ-free (GF) ApcMin/+ and ApcMin/+ ;Il10-/- mice and exposed them to specific
pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon
tumorigenesis significantly correlated with inflammation in SPF-housed ApcMin/+
;Il10-/- , but not in ApcMin/+ mice. In contrast, small intestinal neoplasia
development significantly correlated with age in both ApcMin/+ ;Il10-/- and
ApcMin/+ mice. GF ApcMin/+ ;Il10-/- mice conventionalized by an SPF microbiota
had significantly more colon tumors compared with GF mice. Gnotobiotic studies
revealed that while Fusobacterium nucleatum clinical isolates with FadA and Fap2
adhesins failed to induce inflammation and tumorigenesis, pks+Escherichia coli
promoted tumorigenesis in the ApcMin/+ ;Il10-/- model in a colibactin-dependent
manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest
a distinct etiology of cancers in different locations of the gut, where colon
cancer is primarily driven by inflammation and the microbiome, while age is a
driving force for small intestine cancer. Cancer Res; 77(10); 2620-32. (c)2017
AACR.
PMID- 28416492
TI - Intravitreal triamcinolone acetate for radiation maculopathy recalcitrant to high
dose intravitreal bevacizumab.
AB - BACKGROUND/AIMS: To evaluate the effect of adjuvant intravitreal triamcinolone
acetonide (ITA) for radiation maculopathy (RM) recalcitrant to high-dose
bevacizumab in patients with choroidal melanoma after plaque radiotherapy.
METHODS: Eight eyes of eight patients with RM secondary to plaque radiotherapy
for choroidal melanoma, recalcitrant to high-dose bevacizumab (3.0 mg) were
retrospectively evaluated. Intravitreal injections of ITA (4 mg/0.1 mL) were
performed at 4-week to 16-week intervals as an adjunct to continued bevacizumab
therapy. Change in central foveal thickness (CFT) as measured by optical
coherence tomography and change in visual acuity (VA) were the main outcome
measures. RESULTS: At the time of diagnosis of choroidal melanoma, VA was 20/20
to 20/50 in 88% (n=7) and 20/60 to 20/200 in 12% (n=1). The mean radiation dose
to the fovea was 81 Gy (median 75.2 Gy; range: 22.72-132.8 Gy). The mean onset to
RM was 25 months after plaque therapy (median 25 months; range 12-44 months). At
the time of initiation of ITA, VA was 20/20 to 20/50 in 38% (3/8), and 20/60 to
20/200 in 62% (5/8). After initiation of ITA, VA was stable or improved in 100%
of patients (n=8) at 3 months, 88% at 6 months, 88% at 9 months and 75% at 12
months. Mean CFT was 417 um at ITA initiation, 339 um at 1 month, 355 um at 6
months, 339 um at 9 months and 359 um at 1 year. CONCLUSION: Intravitreal
triamcinolone can be added to preserve vision and decrease macular oedema in
patients with RM recalcitrant to high-dose anti-vascular endothelial growth
factor agents.
PMID- 28416493
TI - Phacoemulsification compared with phacotrabeculectomy surgery: a within-person
observational cohort study.
AB - AIM: To compare reduction in intraocular pressure (IOP) and gain in visual acuity
(VA) following phacotrabeculectomy (PT) and phacoemulsification(phaco) in
Tanzanian patients with primary open angle glaucoma(POAG). SETTING: CCBRT
Hospital, Dar es Salaam, Tanzania. DESIGN: Within-person observational cohort
study. METHODS: Within each patient, one eye had PT and the other phaco. Patients
were followed for up to 5-1/2 years, and IOP and VA in each eye were assessed.
For a small group of patients, two additional postoperative time points were
compared. RESULTS: 52 patients (34 male) with a mean age of 70 years (SD 8 years)
were enrolled in the study. For those with 250 days or more follow-up, both
operations resulted in lower IOPs and improved VA (p<0.001). The average drop in
IOP was 50% (95%CI 45% to 55%) for PT and 41% (95% CI 36% to 46%) for phaco. Mean
IOP was lower in the PT group 12.9 mm Hg vs 16.8 mm Hg (p=0.004). Extended follow
up in nine patients showed a rise in IOP of 1.8 mm Hg for PT and 4.2 mm Hg for
phaco eyes between first (mean, 337 days) and second (mean 1482 days) follow-up
(p=0.18). CONCLUSION: In this small study in African patients, PT resulted in
lower IOPs than phacoemulsification alone but the difference between the
procedures was relatively small. Phacoemulsification alone was effective in
reducing IOP and improving VA for several years in this population. Given the
relative simplicity of phacoemulsification, it is a therapeutic option worthy of
consideration in some settings.
PMID- 28416494
TI - Long-term clinical course of normotensive preperimetric glaucoma.
AB - AIMS: To evaluate the long-term clinical course of normotensive preperimetric
glaucoma (PPG). METHODS: We retrospectively analysed 130 eyes of 130 patients
initially diagnosed as having preperimetric normal tension glaucoma and followed
these cases for at least 5 years with reliable visual field (VF) examinations by
standard automated perimetry. When the VF defect (VFD) met Anderson-Patella's
criteria on three or more consecutive examinations, and consistently met the
criteria on subsequent examinations, we concluded that a glaucomatous VFD was
present. Predictive factors for developing a VFD were assessed. RESULTS: Seventy
one eyes (54.6%) developed a glaucomatous VFD during the follow-up period. The
mean deviation slope varied from -0.90 to 0.41 dB/year. A Cox proportional hazard
model showed that having a greater initial pattern SD (p=0.005), the presence of
optic disc haemorrhage (p=0.022) and higher mean intraocular pressure (IOP) prior
to developing a VFD (p=0.039) were related to developing a VFD. CONCLUSIONS: Our
findings confirmed that the mean IOP, but not the IOP fluctuation, is strongly
associated with the development of a VFD in cases of PPG.
PMID- 28416495
TI - Ultrastructural study of peripheral and central stroma of keratoconus cornea.
AB - PURPOSE: Assess the lamellar organisation of the peripheral and central stroma of
the keratoconus (KC) and normal cornea. METHODS: Five normal and three KC corneas
were fixed in 2.5% glutaraldehyde and processed for electron microscopy. The
ultrathin sections were observed under JEOL 1400 TEM, and digital images were
taken with a bottom-mounted 11-megapixel Quamisa camera, using the iTEM software.
Measurements of the lamellae were carried out using the iTEM software.
Statistical analysis was performed using the SPSS software. RESULTS: The lamellar
organisation at the centre and periphery of the KC cornea was disrupted by the
presence of multiple undulations, which were more aggressive at the posterior
stroma. Among the KC cornea, the mean lamellar thickness of the peripheral middle
(1030.32+/-86.25 nm) and posterior (615.68+/-30.94 nm) stroma was also
significantly (p<0.05) thinner than their corresponding areas of the central KC
cornea (1151.1+/-48 nm; 783.57+/-31.10 nm). At the periphery of KC cornea, just
above the Descemet's membrane (DM), small undulations appeared to emerge out from
the DM. Furthermore, the anterior stroma of the peripheral cornea contained
several lamellar sutures. The mean lamellar thickness of the peripheral and
central KC cornea was significantly (p<0.0001) thinner than the corresponding
areas of the normal cornea. CONCLUSION: The present study reveals the involvement
of lamellae in the peripheral stroma in the pathogenicity of the KC cornea. The
emergence of small undulations in the DM suggests that the formation of
undulation might be starting from the DM.
PMID- 28416496
TI - Long-term cost reduction of routine medications following a residential programme
combining physical activity and nutrition in the treatment of type 2 diabetes: a
prospective cohort study.
AB - OBJECTIVES: To demonstrate that lifestyle modifications will reduce the cost of
routine medications in individuals with type 2 diabetes (T2D), through a
mechanism involving glycaemic control. DESIGN: A within-trial cost-medication
analysis with a 1-year time horizon. SETTING: Controlled environment within the
spa resort of Chatel-Guyon, France. PARTICIPANTS: Twenty-nine participants (aged
50-70 years) with T2D. INTERVENTIONS: A 1-year follow-up intervention, beginning
with a 3-week residential programme combining high exercise volume (15-20
hours/week), restrictive diet (-500 kcal/day) and education. Participants
continued their routine medication, independently managed by their general
practitioner. MAIN OUTCOME MEASURES: Number of medications, number of pills, cost
of medications and health-related outcomes. RESULTS: Twenty-six participants
completed the 1-year intervention. At 1 year, 14 patients out of 26 (54%)
stopped/decreased their medications whereas only 5 (19%) increased or introduced
new drugs (chi2=6.3, p=0.02). The number of pills per day decreased by 1.3+/-0.3
at 12 months (p<0.001). The annual cost of medications for T2D were lower at 1
year (?135.1+/-43.9) versus baseline (?212.6+/-35.8) (p=0.03). The regression
coefficients on costs of routine medication were 0.507 (95% CI 0.056 to 0.959,
p=0.027) for HbA1c and 0.156 (95% CI -0.010 to 0.322, p=0.06) for blood glucose
levels. Diabetics patients with HbA1c >6.5% in the highest (last) quartile
doubled their routine medication costs (66% vs 33%, p=0.037). CONCLUSIONS:
Individuals with T2D reduced routine medication costs following a long-term
lifestyle intervention that started with a 3-week residential programme.
Combining high exercise volume, restrictive diet and education effectively
supported the health of T2D. The main factor explaining reduced medication costs
was better glycaemic control, independent of weight changes. Despite limitations
precluding generalisability, cost-effective results of reduced medication should
contribute to the evidence base required to promote lifestyle interventions for
individuals with T2D. TRIAL REGISTRATION NUMBER: NCT00917917; Post-results.
PMID- 28416497
TI - Prognostication in critically ill patients with severe traumatic brain injury:
the TBI-Prognosis multicentre feasibility study.
AB - OBJECTIVE: Severe traumatic brain injury is a significant cause of morbidity and
mortality in young adults. Assessing long-term neurological outcome after such
injury is difficult and often characterised by uncertainty. The objective of this
feasibility study was to establish the feasibility of conducting a large,
multicentre prospective study to develop a prognostic model of long-term
neurological outcome in critically ill patients with severe traumatic brain
injury. DESIGN: A prospective cohort study. SETTING: 9 Canadian intensive care
units enrolled patients suffering from acute severe traumatic brain injury.
Clinical, biological, radiological and electrophysiological data were
systematically collected during the first week in the intensive care unit.
Mortality and functional outcome (Glasgow Outcome Scale extended) were assessed
on hospital discharge, and then 3, 6 and 12 months following injury. OUTCOMES:
The compliance to protocolised test procedures was the primary outcome. Secondary
outcomes were enrolment rate and compliance to follow-up. RESULTS: We
successfully enrolled 50 patients over a 12-month period. Most patients were male
(80%), with a median age of 45 years (IQR 29.0-60.0), a median Injury Severity
Score of 38 (IQR 25-50) and a Glasgow Coma Scale of 6 (IQR 3-7). Mortality was
38% (19/50) and most deaths occurred following a decision to withdraw life
sustaining therapies (18/19). The main reasons for non-enrolment were the time
window for inclusion being after regular working hours (35%, n=23) and oversight
(24%, n=16). Compliance with protocolised test procedures ranged from 92% to 100%
and enrolment rate was 43%. No patients were lost to follow-up at 6 months and 2
were at 12 months. CONCLUSIONS: In this multicentre prospective feasibility
study, we achieved feasibility objectives pertaining to compliance to test,
enrolment and follow-up. We conclude that the TBI-Prognosis prospective
multicentre study in severe traumatic brain injury patients in Canada is
feasible.
PMID- 28416498
TI - Deprescribing anticholinergic and sedative medicines: protocol for a Feasibility
Trial (DEFEAT-polypharmacy) in residential aged care facilities.
AB - INTRODUCTION: Targeted deprescribing of anticholinergic and sedative medicines
can lead to positive health outcomes in older people; as they have been
associated with cognitive and physical functioning decline. This study will
examine whether the proposed intervention is feasible at reducing the
prescription of anticholinergic and sedative medicines in older people. METHODS
AND ANALYSIS: The Standard Protocol Items: Recommendations for Interventional
trials (SPIRIT checklist) was used to develop and report the protocol. Single
group (precomparison and postcomparison) feasibility study design. STUDY
POPULATION: 3 residential care homes have been recruited. INTERVENTION: This will
involve a New Zealand registered pharmacist using peer-reviewed deprescribing
guidelines, to recommend to general practitioners (GPs), sedative and
anticholinergic medicines that can be deprescribed. The cumulative use of
anticholinergic and sedative medicines for each participant will be quantified,
using the Drug Burden Index (DBI). OUTCOMES: The primary outcome will be the
change in the participants' DBI total and DBI PRN 3 and 6 months after
implementing the deprescribing intervention. Secondary outcomes will include the
number of recommendations taken up by the GP, participants' cognitive
functioning, depression, quality of life, activities of daily living and number
of falls. DATA COLLECTION POINTS: Participants' demographic and clinical data
will be collected at the time of enrolment, along with the DBI. Outcome measures
will be collected at the time of enrolment, 3 and 6 months' postenrolment. ETHICS
AND DISSEMINATION: Ethics approval has been granted by the Human Disability and
Ethics Committee. Ethical approval number (16/NTA/61). TRIAL REGISTRATION NUMBER:
Pre-results; ACTRN12616000721404.
PMID- 28416499
TI - Has the role of personal income in alcohol drinking among teenagers changed
between 1983 and 2013: a series of nationally representative surveys in Finland.
AB - OBJECTIVE: Affordability is known to be a key determinant of alcohol consumption,
possibly even more important in adolescence. Relating adolescent drinking pattern
developments over a period of time to trends in adolescent income can yield
information on the significance of parental control of adolescent income. DESIGN:
Biannual repeated cross-sectional surveys. SETTING: Nationally representative
samples. PARTICIPANTS: 14-year-old adolescents in the period 1983-2013 in Finland
(N=33 771). RESULTS: Adolescents' alcohol drinking pattern was significantly
associated with their disposable income. The OR for monthly drunkenness versus
abstinence was 6.6 (95% CI 5.0 to 8.8) among girls and 9.0 (6.3 to 13.0) among
boys in the highest income group compared with the lowest. However, the
association between income and drinking pattern weakened considerably during the
30-year period. CONCLUSIONS: Disposable income has been a significant predictor
of adolescent alcohol drinking in the past 30 years. However, in the recent
years, the amount of disposable money has decreased in importance.
PMID- 28416500
TI - Cluster randomised controlled trial of a consumer behaviour intervention to
improve healthy food purchases from online canteens: study protocol.
AB - INTRODUCTION: School canteens represent an opportune setting in which to deliver
public health nutrition strategies given their wide reach, and frequent use by
children. Online school canteen ordering systems, where students order and pay
for their lunch online, provide an avenue to improve healthy canteen purchases
through the application of consumer behaviour strategies that impact on
purchasing decisions. The aim of this study is to assess the efficacy of a
consumer behaviour intervention implemented in an online school canteen ordering
system in reducing the kilojoule, saturated fat, sugar and sodium content of
primary student lunch orders. METHODS AND ANALYSIS: The study will employ a
cluster randomised controlled trial design. Approximately 1040 students (aged 5
12 years) from 10 primary schools in New South Wales, Australia, currently using
an online canteen ordering system will be invited to participate. Schools will be
randomised in a 1:1 ratio to receive either the intervention (enhanced system) or
control (standard online ordering only). The intervention will include evidence
based strategies shown to influence healthy food purchasing (strategies targeting
availability, menu labelling, placement and prompting). The primary outcomes of
the trial will be the mean content per student online lunch order of (1) energy
(kJ), (2) saturated fat (g), (3) sugar (g) and (4) sodium (mg). The impact of the
intervention will be determined by between-group assessment of the nutritional
content of lunch purchases over a 2-month period postintervention initiation.
ETHICS AND DISSEMINATION: The study was approved by the Hunter New England Human
Research Ethics Committee, University of Newcastle Human Research Ethics
Committee and New South Wales Department of Education and School Communities.
Study findings will be disseminated widely through peer-reviewed publications and
relevant presentations in international conferences and to stakeholders. TRIAL
REGISTRATION NUMBER: ACTRN12616000499482.
PMID- 28416502
TI - Interim PET-driven strategy in de novo diffuse large B-cell lymphoma: do we trust
the driver?
AB - 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) has become a
central tool for both accurate initial staging and determination of prognosis
after treatment of diffuse large B-cell lymphoma (DLBCL). However, the role of
PET during treatment (iPET) in daily practice remains a matter of significant
debate. This perspective reviews the published studies on iPET in DLBCL,
including the methods used to analyze iPET, its timing, and studies of iPET
driven therapy to illuminate where daily practice may benefit from the use of
iPET. When performed after 2 and/or 4 courses of immunochemotherapy, iPET has a
very good negative predictive value, utilizing both visual (qualitative) and
semiquantitative methods. The visual method accurately predicts outcome for
patients with limited disease. The semiquantitative method, eg, the change of the
difference of maximum standardized uptake value (DeltaSUVmax), is for patients
with advanced DLBCL, for whom iPET identifies patients with very good outcome
with continuation of standard therapy. A low DeltaSUVmax also helps identify
patients with a risk for relapse averaging 50% and warrants review of their
scheduled therapy. To date, no trial has demonstrated the superiority of an iPET
driven strategy in DLBCL. However, the very good negative and good positive
predictive values of iPET support its use in daily practice as a better
predictive tool than contrast-enhanced computed tomographic scan for therapeutic
decision making.
PMID- 28416501
TI - Protocol for a placebo-controlled, within-participants crossover trial evaluating
the efficacy of intranasal oxytocin to improve pain and function among women with
chronic pelvic musculoskeletal pain.
AB - INTRODUCTION: This protocol presents the rationale and design for a trial
evaluating the efficacy of intranasal oxytocin in improving pain and function
among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide
traditionally recognised for involvement in labour, delivery and lactation. Novel
evidence suggests that oxytocin decreases pain sensitivity in humans. While
oxytocin administration has been reported to lower pain sensitivity among
patients experiencing chronic back pain, headache, constipation and colon pain,
no research has evaluated the association between intranasal oxytocin and chronic
pelvic musculoskeletal pain. The association between oxytocin and pain may differ
in women with chronic pelvic musculoskeletal pain relative to other chronic pain
conditions because of the abundance of oxytocin receptors in the uterus. METHODS
AND ANALYSIS: This is a prospective, randomised, placebo-controlled, double
blind, within-participants crossover trial. 50 women with chronic pelvic
musculoskeletal pain will be recruited through a local chronic pain centre and
gynaecology clinics. Women will complete baseline measures and be randomised to
an experimental or control condition that involve 2 weeks of self-administering
twice-daily doses of 24 IU intranasal oxytocin or placebo, respectively. Women
will then undergo a 2-week washout period before crossing over to receive the
condition that they had not yet received. The primary outcome will be pain and
function measured using the Brief Pain Inventory-Short Form. Secondary outcomes
include emotional function, sleep disturbance and global impression of change.
This trial will provide data on the 14-day safety and side-effect profile of
intranasal oxytocin self-administered as an adjuvant treatment for chronic pelvic
musculoskeletal pain. ETHICS AND DISSEMINATION: This trial was granted approval
from Health Canada and the University of Calgary Conjoint Health Research Ethics
Board, and is registered online at ClinicalTrials.gov (#NCT02888574). Results
will be disseminated to healthcare professionals through peer-reviewed
publications and to the general public through press releases. TRIAL REGISTRATION
NUMBER: NCT02888574; Pre-results.
PMID- 28416503
TI - Invariant natural killer T cells ameliorate murine chronic GVHD by expanding
donor regulatory T cells.
AB - Chronic graft-versus-host-disease (cGVHD) can cause multiorgan system disease,
typically with autoimmune-like features, resulting in high mortality and
morbidity caused by treatment limitations. Invariant natural killer T cells
(iNKTs), a small population characterized by expression of a semi-invariant T
cell receptor, rapidly produce copious amounts of diverse cytokines on activation
that exert potent immune regulatory function. Here, we show that iNKTs are
significantly reduced in a cGVHD murine model that recapitulates several aspects
of autoimmunity and organ fibrosis observed in patients with cGVHD. Low iNKT
infused doses effectively prevented and, importantly, reversed established cGVHD,
as did third-party iNKTs. iNKTs suppressed the autoimmune response by reducing
the germinal center (GC) reaction, which was associated with an increase in total
Tregs and follicular Tregs (Tfr) that control the GC reaction, along with
pathogenic antibody production. Treg depletion during iNKT infusions completely
abolished iNKT efficacy in treating cGVHD. iNKT cell interleukin 4 production and
GC migration were critical to cGVHD reversal. In vivo stimulation of iNKT cells
by alpha-galactosyl-ceramide was effective in both preventing and treating cGVHD.
Together, this study demonstrates iNKT deficiency in cGVHD mice and highlights
the key role of iNKTs in regulating cGVHD pathogenesis and as a potentially novel
prophylactic and therapeutic option for patients with cGVHD.
PMID- 28416504
TI - Introduction to a series of reviews on clinical platelet disorders.
PMID- 28416505
TI - Hematopoietic transcription factor mutations: important players in inherited
platelet defects.
AB - Transcription factors (TFs) are proteins that bind to specific DNA sequences and
regulate expression of genes. The molecular and genetic mechanisms in most
patients with inherited platelet defects are unknown. There is now increasing
evidence that mutations in hematopoietic TFs are an important underlying cause
for defects in platelet production, morphology, and function. The hematopoietic
TFs implicated in patients with impaired platelet function and number include
runt-related transcription factor 1, Fli-1 proto-oncogene, E-twenty-six (ETS)
transcription factor (friend leukemia integration 1), GATA-binding protein 1,
growth factor independent 1B transcriptional repressor, ETS variant 6, ecotropic
viral integration site 1, and homeobox A11. These TFs act in a combinatorial
manner to bind sequence-specific DNA within promoter regions to regulate lineage
specific gene expression, either as activators or repressors. TF mutations induce
rippling downstream effects by simultaneously altering the expression of multiple
genes. Mutations involving these TFs affect diverse aspects of megakaryocyte
biology, and platelet production and function, culminating in thrombocytopenia
and platelet dysfunction. Some are associated with predisposition to hematologic
malignancies. These TF variants may occur more frequently in patients with
inherited platelet defects than generally appreciated. This review focuses on
alterations in hematopoietic TFs in the pathobiology of inherited platelet
defects.
PMID- 28416506
TI - Clinical updates in adult immune thrombocytopenia.
AB - Immune thrombocytopenia (ITP) occurs in 2 to 4/100 000 adults and results in
variable bleeding symptoms and thrombocytopenia. In the last decade, changes in
our understanding of the pathophysiology of the disorder have led to the
publication of new guidelines for the diagnosis and management of ITP and
standards for terminology. Current evidence supports alternatives to splenectomy
for second-line management of patients with persistently low platelet counts and
bleeding. Long-term follow-up data suggest both efficacy and safety, in
particular, for the thrombopoietin receptor agonists and the occurrence of late
remissions. Follow-up of patients who have undergone splenectomy for ITP reveals
significant potential risks that should be discussed with patients and may
influence clinician and patient choice of second-line therapy. Novel therapeutics
are in development to address ongoing treatment gaps.
PMID- 28416507
TI - Thrombotic thrombocytopenic purpura.
AB - Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening
thrombotic microangiopathy characterized by microangiopathic hemolytic anemia,
severe thrombocytopenia, and organ ischemia linked to disseminated microvascular
platelet rich-thrombi. TTP is specifically related to a severe deficiency in
ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats,
member 13), the specific von Willebrand factor-cleaving protease. ADAMTS13
deficiency is most frequently acquired via ADAMTS13 autoantibodies, but rarely,
it is inherited via mutations of the ADAMTS13 gene. The first acute episode of
TTP usually occurs during adulthood, with a predominant anti-ADAMTS13 autoimmune
etiology. In rare cases, however, TTP begins as soon as childhood, with frequent
inherited forms. TTP is ~2-fold more frequent in women, and its outcome is
characterized by a relapsing tendency. Rapid recognition of TTP is crucial to
initiate appropriate treatment. The first-line therapy for acute TTP is based on
daily therapeutic plasma exchange supplying deficient ADAMTS13, with or without
steroids. Additional immune modulators targeting ADAMTS13 autoantibodies are
mainly based on steroids and the humanized anti-CD20 monoclonal antibody
rituximab. In refractory or unresponsive TTP, more intensive therapies including
twice-daily plasma exchange; pulses of cyclophosphamide, vincristine, or
cyclosporine A; or salvage splenectomy are considered. New drugs including N
acetylcysteine, bortezomib, recombinant ADAMTS13, and caplacizumab show promise
in the management of TTP. Also, long-term follow-up of patients with TTP is
crucial to identify the occurrence of other autoimmune diseases, to control
relapses, and to evaluate psychophysical sequelae. Further development of both
patients' registries worldwide and innovative drugs is still needed to improve
TTP management.
PMID- 28416509
TI - None of the above: thrombotic microangiopathy beyond TTP and HUS.
AB - Acquired thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome
(HUS) are appropriately at the top of a clinician's differential when a patient
presents with a clinical picture consistent with an acute thrombotic
microangiopathy (TMA). However, there are several additional diagnoses that
should be considered in patients presenting with an acute TMA, especially in
patients with nondeficient ADAMTS13 (a disintegrin and metalloproteinase with a
thrombospondin type 1 motif, member 13) activity (>10%). An increased awareness
of drug-induced TMA is also essential because the key to their diagnosis more
often is an appropriately detailed medical history to inquire about potential
exposures. Widespread inflammation and endothelial damage are central in the
pathogenesis of the TMA, with the treatment directed at the underlying disease if
possible. TMA presentations in the critically ill, drug-induced TMA, cancer
associated TMA, and hematopoietic transplant-associated TMA (TA-TMA) and their
specific treatment, where applicable, will be discussed in this manuscript. A
complete assessment of all the potential etiologies for the TMA findings
including acquired TTP will allow for a more accurate diagnosis and prevent
prolonged or inappropriate treatment with plasma exchange therapy when it is less
likely to be successful.
PMID- 28416508
TI - HUS and atypical HUS.
AB - Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by
intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is
usually categorized as typical, caused by Shiga toxin-producing Escherichia coli
(STEC) infection, as atypical HUS (aHUS), usually caused by uncontrolled
complement activation, or as secondary HUS with a coexisting disease. In recent
years, a general understanding of the pathogenetic mechanisms driving HUS has
increased. Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with
STEC, whereas aHUS is associated primarily with mutations or autoantibodies
leading to dysregulated complement activation. Among the 30% to 50% of patients
with HUS who have no detectable complement defect, some have either impaired
diacylglycerol kinase epsilon (DGKepsilon) activity, cobalamin C deficiency, or
plasminogen deficiency. Some have secondary HUS with a coexisting disease or
trigger such as autoimmunity, transplantation, cancer, infection, certain
cytotoxic drugs, or pregnancy. The common pathogenetic features in STEC-HUS,
aHUS, and secondary HUS are simultaneous damage to endothelial cells,
intravascular hemolysis, and activation of platelets leading to a procoagulative
state, formation of microthrombi, and tissue damage. In this review, the
differences and similarities in the pathogenesis of STEC-HUS, aHUS, and secondary
HUS are discussed. Common for the pathogenesis seems to be the vicious cycle of
complement activation, endothelial cell damage, platelet activation, and
thrombosis. This process can be stopped by therapeutic complement inhibition in
most patients with aHUS, but usually not those with a DGKepsilon mutation, and
some patients with STEC-HUS or secondary HUS. Therefore, understanding the
pathogenesis of the different forms of HUS may prove helpful in clinical
practice.
PMID- 28416510
TI - Erythrocyte sialoglycoproteins engage Siglec-9 on neutrophils to suppress
activation.
AB - Healthy blood neutrophils are functionally quiescent in the bloodstream, have a
short lifespan, and exit the circulation to carry out innate immune functions, or
undergo rapid apoptosis and macrophage-mediated clearance to mitigate host tissue
damage. Limitation of unnecessary intravascular neutrophil activation is also
important to prevent serious inflammatory pathologies. Because neutrophils become
easily activated after purification, we carried out ex vivo comparisons with
neutrophils maintained in whole blood. We found a difference in activation state,
with purified neutrophils showing signs of increased reactivity: shedding of l
selectin, CD11b upregulation, increased oxidative burst, and faster progression
to apoptosis. We discovered that erythrocytes suppressed neutrophil activation ex
vivo and in vitro, including reduced l-selectin shedding, oxidative burst,
chemotaxis, neutrophil extracellular trap formation, bacterial killing, and
induction of apoptosis. Selective and specific modification of sialic acid side
chains on erythrocyte surfaces with mild sodium metaperiodate oxidation followed
by aldehyde quenching with 4-methyl-3-thiosemicarbazide reduced neutrophil
binding to erythrocytes and restored neutrophil activation. By enzyme-linked
immunosorbent assay and immunofluorescence, we found that glycophorin A, the most
abundant sialoglycoprotein on erythrocytes, engaged neutrophil Siglec-9, a sialic
acid-recognizing receptor known to dampen innate immune cell activation. These
studies demonstrate a previously unsuspected role for erythrocytes in suppressing
neutrophils ex vivo and in vitro and help explain why neutrophils become easily
activated after separation from whole blood. We propose that a sialic acid-based
"self-associated molecular pattern" on erythrocytes also helps maintain
neutrophil quiescence in the bloodstream. Our findings may be relevant to some
prior experimental and clinical studies of neutrophils.
PMID- 28416511
TI - Heparin-induced thrombocytopenia.
AB - Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin
therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin.
Pathogenic antibodies to PF4/heparin bind and activate cellular FcgammaRIIA on
platelets and monocytes to propagate a hypercoagulable state culminating in life
threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies
develop commonly after heparin exposure, but only a subset of sensitized patients
progress to life-threatening complications of thrombocytopenia and thrombosis.
Recent scientific developments have clarified mechanisms underlying PF4/heparin
immunogenicity, disease susceptibility, and clinical manifestations of disease.
Insights from clinical and laboratory findings have also been recently harnessed
for disease prevention. This review will summarize our current understanding of
HIT by reviewing pathogenesis, essential clinical and laboratory features, and
management.
PMID- 28416513
TI - What is broad-range 16S rDNA PCR?
PMID- 28416512
TI - Investigating the Genetic Architecture of the PR Interval Using Clinical
Phenotypes.
AB - BACKGROUND: One potential use for the PR interval is as a biomarker of disease
risk. We hypothesized that quantifying the shared genetic architectures of the PR
interval and a set of clinical phenotypes would identify genetic mechanisms
contributing to PR variability and identify diseases associated with a genetic
predictor of PR variability. METHODS AND RESULTS: We used ECG measurements from
the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63
genetically modulated diseases from the eMERGE network (Electronic Medical
Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG)
between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the
63 phenotypes. The PR segment was genetically correlated with atrial fibrillation
(rG=-0.88; P=0.0009). An analysis of metabolic phenotypes in ARIC also showed
that the P wave was genetically correlated with waist circumference (rG=0.47;
P=0.02). A genetically predicted PR interval phenotype based on 645 714 single
nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89
per SD change; 95% confidence interval, 0.83-0.95; P=0.0006). The differing
pattern of associations among the PR phenotypes is consistent with analyses that
show that the genetic correlation between the P wave and PR segment was not
significantly different from 0 (rG=-0.03 [0.16]). CONCLUSIONS: The genetic
architecture of the PR interval comprises modulators of atrial fibrillation risk
and obesity.
PMID- 28416514
TI - Optical Mapping Approaches on Muscleblind-Like Compound Knockout Mice for
Understanding Mechanistic Insights Into Ventricular Arrhythmias in Myotonic
Dystrophy.
AB - BACKGROUND: Cardiac arrhythmias are common causes of death in patients with
myotonic dystrophy (dystrophia myotonica [DM]). Evidence shows that atrial
tachyarrhythmia is an independent risk factor for sudden death; however, the
relationship is unclear. METHODS AND RESULTS: Control wild-type (Mbnl1+/+;
Mbnl2+/+ ) and DM mutant (Mbnl1-/-; Mbnl2+/- ) mice were generated by crossing
double heterozygous knockout (Mbnl1+/-; Mbnl2+/- ) mice. In vivo
electrophysiological study and optical mapping technique were performed to
investigate mechanisms of ventricular tachyarrhythmias. Transmission electron
microscopy scanning was performed for myocardium ultrastructural analysis. DM
mutant mice were more vulnerable to anesthesia medications and program electrical
pacing: 2 of 12 mice had sudden apnea and cardiac arrest during premedication of
general anesthesia; 9 of the remaining 10 had atrial tachycardia and/or
atrioventricular block, but none of the wild-type mice had spontaneous
arrhythmias; and 9 of 10 mice had pacing-induced ventricular tachyarrhythmias,
but only 1 of 14 of the wild-type mice. Optical mapping studies revealed
prolonged action potential duration, slower conduction velocity, and steeper
conduction velocity restitution curves in the DM mutant mice than in the wild
type group. Spatially discordant alternans was more easily inducible in DM mutant
than wild-type mice. Transmission electron microscopy showed disarranged
myofibrils with enlarged vacuole-occupying mitochondria in the DM mutant group.
CONCLUSIONS: This DM mutant mouse model presented with clinical myofibril
ultrastructural abnormality and cardiac arrhythmias, including atrial
tachyarrhythmias, atrioventricular block, and ventricular tachyarrhythmias.
Optical mapping studies revealed prolonged action potential duration and slow
conduction velocity in the DM mice, leading to vulnerability of spatially
discordant alternans and ventricular arrhythmia induction to pacing.
PMID- 28416515
TI - Multivariate modelling of faecal bacterial profiles of patients with IBS predicts
responsiveness to a diet low in FODMAPs.
AB - OBJECTIVE: The effects of dietary interventions on gut bacteria are ambiguous.
Following a previous intervention study, we aimed to determine how differing
diets impact gut bacteria and if bacterial profiles predict intervention
response. DESIGN: Sixty-seven patients with IBS were randomised to traditional
IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides
and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4
days during screening and intervention. Faecal samples and IBS Symptom Severity
Score (IBS-SSS) reports were collected before (baseline) and after intervention.
A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial
composition. Per protocol analysis was performed on 61 patients from whom
microbiome data were available. RESULTS: Responders (reduced IBS-SSS by >=50) to
low FODMAP, but not traditional, dietary intervention were discriminated from non
responders before and after intervention based on faecal bacterial profiles.
Bacterial abundance tended to be higher in non-responders to a low FODMAP diet
compared with responders before and after intervention. A low FODMAP intervention
was associated with an increase in Dysbiosis Index (DI) scores in 42% of
patients; while decreased DI scores were recorded in 33% of patients following a
traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional
IBS diet had higher DI scores than responders at baseline. Finally, while a
traditional IBS diet was not associated with significant reduction of
investigated bacteria, a low FODMAP diet was associated with reduced
Bifidobacterium and Actinobacteria in patients, correlating with lactose
consumption. CONCLUSIONS: A low FODMAP, but not a traditional IBS diet may have
significant impact on faecal bacteria. Responsiveness to a low FODMAP diet
intervention may be predicted by faecal bacterial profiles. TRIAL REGISTRATION
NUMBER: NCT02107625.
PMID- 28416517
TI - SUA levels should not be maintained <3 mg/dL for several years. Response to
'EULAR gout treatment guidelines by Richette et al: uric acid and neurocognition
by Singh et al'.
PMID- 28416518
TI - The influence of discrepant imaging judgements on the classification of axial
spondyloarthritis is limited: a replication in the SpondyloArthritis Caught Early
(SPACE) cohort.
PMID- 28416519
TI - Time in the Therapeutic Range for Patients Taking Warfarin in Clinical Trials:
Useful, but Also Misleading, Misused, and Overinterpreted.
PMID- 28416520
TI - Engagement, Research, and Evidence: Leveraging the National Patient-Centered
Clinical Research Network for Better Cardiovascular Health.
PMID- 28416516
TI - Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis
of neutrophil-mediated autoimmune vasculitis.
AB - OBJECTIVES: Inappropriate activation of neutrophils plays a pathological role in
antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim
of this study was to investigate the functions of semaphorin 4D (SEMA4D) in
regulation of neutrophil activation, and its involvement in AAV pathogenesis.
METHODS: Serum levels of soluble SEMA4D were evaluated by ELISA. Blood cell
surface expression of membrane SEMA4D was evaluated by flow cytometry. To
determine the functional interactions between neutrophil membrane SEMA4D and
endothelial plexin B2, wild-type and SEMA4D-/- mice neutrophils were cultured
with an endothelial cell line (MS1) stained with SYTOX green, and subjected to
neutrophil extracellular trap (NET) formation assays. The efficacy of treating
human neutrophils with recombinant plexin B2 was assessed by measuring the
kinetic oxidative burst and NET formation assays. RESULTS: Serum levels of
soluble SEMA4D were elevated in patients with AAV and correlated with disease
activity scores. Cell-surface expression of SEMA4D was downregulated in
neutrophils from patients with AAV, a consequence of proteolytic cleavage of
membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial
cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells,
and this interaction decreased NET formation. Recombinant plexin B2 suppressed
neutrophil Rac1 activation through SEMA4D's intracellular domain, and inhibited
pathogen-induced or ANCA-induced oxidative burst and NET formation. CONCLUSIONS:
Neutrophil surface SEMA4D functions as a negative regulator of neutrophil
activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may
amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising
biomarker and potential therapeutic target for AAV.
PMID- 28416521
TI - Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): The Past,
Present, and Future Management.
PMID- 28416522
TI - High-Sensitive Cardiac Troponin for Prediction of Clinical Heart Failure: Are We
Ready for Prime Time?
PMID- 28416523
TI - Measuring Pulmonary Artery Pressures in Heart Failure: A New Useful Diagnostic
Tool?
PMID- 28416525
TI - Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced
Ejection Fraction.
AB - Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF)
frequently coexist, and each complicates the course and treatment of the other.
Recent population-based studies have demonstrated that the 2 conditions together
increase the risk of stroke, heart failure hospitalization, and all-cause
mortality, especially soon after the clinical onset of AF. Guideline-directed
pharmacological therapy for HFrEF is important; however, although there are
various treatment modalities for AF, there is no clear consensus on how best to
treat AF with concomitant HFrEF. This in-depth review discusses the available
data for the treatment of AF in the setting of HFrEF, focuses on areas where more
investigation is necessary, examines the clinical implications of randomized and
observational clinical trials, and presents suggestions for individualized
treatment strategies for specific patient groups.
PMID- 28416524
TI - Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in
Type 1 Diabetes Mellitus.
AB - BACKGROUND: Individuals with type 1 diabetes mellitus (T1DM) have a high risk of
cardiovascular complications, but it is unknown to what extent fulfilling all
cardiovascular treatment goals is associated with residual risk of mortality and
cardiovascular outcomes in those with T1DM compared with the general population.
METHODS: We included all patients >=18 years of age with T1DM who were registered
in the Swedish National Diabetes Register from January 1, 1998, through December
31, 2014, a total of 33 333 patients, each matched for age and sex with 5
controls without diabetes mellitus randomly selected from the population.
Patients with T1DM were categorized according to number of risk factors not at
target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density
lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial
infarction, heart failure hospitalization, and stroke was examined in relation to
the number of risk factors at target. RESULTS: The mean follow-up was 10.4 years
in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus
and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for
each additional risk factor not at target. Adjusted hazard ratios for patients
achieving all risk factor targets compared with controls were 1.31 (95%
confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15
2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure
hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for
patients versus controls with none of the risk factors meeting target was 7.33
(95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for
acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure
hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke. CONCLUSIONS: A steep
graded association exists between decreasing number of cardiovascular risk
factors at target and major adverse cardiovascular outcomes among patients with
T1DM. However, risks for all outcomes were numerically higher for patients with
T1DM compared with controls, even when all risk factors were at target, with risk
for acute myocardial infarction and heart failure hospitalization statistically
significantly higher.
PMID- 28416526
TI - Some Common Ground Emerges in Debate Over ECGs for Athletes.
PMID- 28416527
TI - Letter by Irfan Regarding Article, "Assessment of the European Society of
Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial
Infarction".
PMID- 28416528
TI - Letter by Mueller and Roffi Regarding Article, "Assessment of the European
Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute
Myocardial Infarction".
PMID- 28416529
TI - Response by Than et al to Letter Regarding Article, "Assessment of the European
Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute
Myocardial Infarction".
PMID- 28416530
TI - Letter by Hermida et al Regarding Article, "The Heart's Circadian Rhythms Point
to Potential Treatment Strategies".
PMID- 28416531
TI - Treatment Deintensification Is Uncommon in Adults With Type 2 Diabetes Mellitus:
A Retrospective Cohort Study.
AB - BACKGROUND: Whether treatment deintensification in Americans with diabetes
mellitus varies by glycemic control, health status, and calendar year
(before/after February 2008 when safety concerns about intensive glucose control
were reported in the ACCORD trial [Action to Control Cardiovascular Risk in
Diabetes]) is unclear. METHODS AND RESULTS: We defined deintensification as
discontinuation or dosage decrease of at least 1 glycemic medication without
addition of, or uptitration of, another agent in the 120 days after the index
glycosylated hemoglobin (HbA1C) measurement. Of 99 694 individuals (mean age 54
years) in this retrospective cohort study being actively treated for new diabetes
mellitus (50% 1 drug, 33% 2 drugs, and 17% >=3 drugs), 12 921 (13.0%) had HbA1C
<6% after 1 year, 19 670 (19.7%) had HbA1C 6.0% to 6.4%, 35 012 (35.1%) had HbA1C
6.5% to 7.5%, and 32 091 (32.2%) had HbA1C >7.5%. Glycemic therapy was
deintensified in 18.3% of patients (21.2% of frail patients, 19.4% of those with
multiple comorbidities, and 17.7% of otherwise healthy patients) with no gradient
across glycemia levels (20.6% of those with HbA1C<6%, 17.3% of those with HbA1C
6.0%-6.4%, 17.7% of those with HbA1C 6.5%-7.5%, and 18.6% of those with
HbA1C>7.5%). Similar proportions were seen even after exclusion of 26 985
patients being treated with metformin monotherapy: 23.3%, 20.4%, 20.3%, and 20%
across the HbA1C strata. Therapy was deintensified in 22.5% of patients with
index HbA1C <6.0% before February 2008 compared with 19.5% after (P<0.001).
CONCLUSIONS: Among frail patients or those with multiple comorbidities, over
three quarters with low HbA1C did not have their glycemic therapy deintensified,
even after safety concerns were raised in the ACCORD trial.
PMID- 28416532
TI - Diabetes Mellitus Treatment Deintensification: When Well-Controlled Diabetes
Mellitus Becomes Overcontrolled.
PMID- 28416534
TI - Pazopanib-associated posterior reversible encephalopathy syndrome with
intracerebral haemorrhage.
AB - Pazopanib is a tyrosine kinase receptor antagonist used for renal cell carcinoma
and soft tissue sarcoma that inhibits tumour growth and angiogenesis. A common
side effect of pazopanib is hypertension. We report a case of a 69-year-old woman
with clear cell renal cell carcinoma who developed a large right occipital
intracerebral haemorrhage 3 weeks after initiating pazopanib. Although this was
initially suspected to be a haemorrhagic metastasis, MRI revealed bi-occipital
oedema, supporting a diagnosis of posterior reversible encephalopathy syndrome
(PRES). A craniectomy was required. Immunohistochemical stains for renal cell
carcinoma antigen, CA IX and PAX8 were negative. This case suggests that PRES and
intracerebral haemorrhage may result from pazopanib use and are important
complications to consider prior to initiating this agent.
PMID- 28416535
TI - Pneumatic dental extractions: an unusual cause of extensive cervical surgical
emphysema.
AB - A 50-year-old fit and well man presented to the Accident and Emergency Department
in a tertiary centre following lower molar extraction, complaining of voice
hoarseness with neck and facial swelling. Clinical examination along with plain
film radiography revealed pneumomediastinum and extensive cervical surgical
emphysema. He was subsequently admitted for observation and managed
conservatively under the ENT team with input from the maxillofacial and
anaesthetic teams. With supportive treatment only, the emphysema resolved and he
remained well up until discharge.
PMID- 28416533
TI - Capturing in vivo RNA transcriptional dynamics from the malaria parasite
Plasmodium falciparum.
AB - To capture the transcriptional dynamics within proliferating cells, methods to
differentiate nascent transcription from preexisting mRNAs are desired. One
approach is to label newly synthesized mRNA transcripts in vivo through the
incorporation of modified pyrimidines. However, the human malaria parasite,
Plasmodium falciparum, is incapable of pyrimidine salvage for mRNA biogenesis. To
capture cellular mRNA dynamics during Plasmodium development, we engineered
parasites that can salvage pyrimidines through the expression of a single
bifunctional yeast fusion gene, cytosine deaminase/uracil
phosphoribosyltransferase (FCU). We show that expression of FCU allows for the
direct incorporation of thiol-modified pyrimidines into nascent mRNAs. Using
developmental stage-specific promoters to express FCU-GFP enables the
biosynthetic capture and in-depth analysis of mRNA dynamics from subpopulations
of cells undergoing differentiation. We demonstrate the utility of this method by
examining the transcriptional dynamics of the sexual gametocyte stage transition,
a process that is essential to malaria transmission between hosts. Using the
pfs16 gametocyte-specific promoter to express FCU-GFP in 3D7 parasites, we found
that sexual stage commitment is governed by transcriptional reprogramming and
stabilization of a subset of essential gametocyte transcripts. We also measured
mRNA dynamics in F12 gametocyte-deficient parasites and demonstrate that the
transcriptional program required for sexual commitment and maturation is
initiated but likely aborted due to the absence of the PfAP2-G transcriptional
regulator and a lack of gametocyte-specific mRNA stabilization. Biosynthetic
labeling of Plasmodium mRNAs is incredibly versatile, can be used to measure
transcriptional dynamics at any stage of parasite development, and will allow for
future applications to comprehensively measure RNA-protein interactions in the
malaria parasite.
PMID- 28416536
TI - Multiple jaw cysts and ectopic calcification.
PMID- 28416537
TI - Anosmia with hypogonadism: but NOT Kallmann syndrome.
PMID- 28416538
TI - Susceptibility Testing of Common and Uncommon Aspergillus Species against
Posaconazole and Other Mold-Active Antifungal Azoles Using the Sensititre Method.
AB - We tested 59 common and 27 uncommon Aspergillus species isolates for
susceptibility to the mold-active azole antifungal agents itraconazole,
voriconazole, and posaconazole using the Sensititre method. The overall essential
agreement with the CLSI reference method was 96.5% for itraconazole and
posaconazole and was 100% for voriconazole. By the Sensititre method as well as
the CLSI reference method, all of 10 A. fumigatus isolates with a cyp51 mutant
genotype were classified as being non-wild-type isolates (MIC > epidemiological
cutoff value [ECV]) with respect to triazole susceptibility.
PMID- 28416539
TI - Comparison of EUCAST and CLSI Reference Microdilution MICs of Eight Antifungal
Compounds for Candida auris and Associated Tentative Epidemiological Cutoff
Values.
AB - Candida auris is an emerging multidrug-resistant yeast. So far, all but two
susceptibility testing studies have examined <=50 isolates, mostly with the CLSI
method. We investigated CLSI and EUCAST MICs for 123 C. auris isolates and eight
antifungals and evaluated various methods for epidemiological cutoff (ECOFF)
determinations. MICs (in milligrams per liter) were determined using CLSI method
M27-A3, and the EUCAST E.Def 7.3. ANOVA analysis of variance with Bonferroni's
multiple-comparison test and Pearson analysis were used on log2 MICs
(significance at P values of <0.05). The percent agreement (within +/-0 to +/-2 2
fold dilutions) between the methods was calculated. ECOFFs were determined
visually, statistically (using the ECOFF Finder program and MicDat1.23 software
with 95% to 99% endpoints), and via the derivatization method (dECOFFs). The CLSI
and EUCAST MIC distributions were wide, with several peaks for all compounds
except amphotericin B, suggesting possible acquired resistance. Modal MIC,
geometric MIC, MIC50, and MIC90 values were <=1 2-fold dilutions apart, and no
significant differences were found. The quantitative agreement was best for
amphotericin B (80%/97% within +/-1/+/-2 dilutions) and lowest for isavuconazole
and anidulafungin (58%/76% to 75% within +/-1/+/-2 dilutions). We found that
90.2%/100% of the isolates were amphotericin B susceptible based on CLSI/EUCAST
methods, respectively (i.e., with MICs of <=1 mg/liter), and 100%/97.6% were
fluconazole nonsusceptible by CLSI/EUCAST (MICs > 2). The ECOFFs (in milligrams
per liter) were similar across the three different methods for itraconazole
(ranges for CLSI/EUCAST, 0.25 to 0.5/0.5 to 1), posaconazole (0.125/0.125 to
0.25), amphotericin B (0.25 to 0.5/1 to 2), micafungin (0.25 to 0.5), and
anidulafungin (0.25 to 0.5/0.25 to 1). In contrast, the estimated ECOFFs were
dependent on the method applied for voriconazole (1 to 32) and isavuconazole
(0.125 to 4). CLSI and EUCAST MICs were remarkably similar and confirmed uniform
fluconazole resistance and variable acquired resistance to the other agents.
PMID- 28416541
TI - Efflux Attenuates the Antibacterial Activity of Q203 in Mycobacterium
tuberculosis.
AB - New and improved treatments for tuberculosis (TB) are urgently needed. Recently,
it has been demonstrated that verapamil, an efflux inhibitor, can reduce
bacterial drug tolerance caused by efflux pump activity when administered in
combination with available antituberculosis agents. The aim of this study was to
evaluate the effectiveness of verapamil in combination with the antituberculosis
drug candidate Q203, which has recently been developed and is currently under
clinical trials as a potential antituberculosis agent. We evaluated changes in
Q203 activity in the presence and absence of verapamil in vitro using the
resazurin microplate assay and ex vivo using a microscopy-based phenotypic assay
for the quantification of intracellular replicating mycobacteria. Verapamil
increased the potency of Q203 against Mycobacterium tuberculosis both in vitro
and ex vivo, indicating that efflux pumps are associated with the activity of
Q203. Other efflux pump inhibitors also displayed an increase in Q203 potency,
strengthening this hypothesis. Therefore, the combination of verapamil and Q203
may be a promising combinatorial strategy for anti-TB treatment to accelerate the
elimination of M. tuberculosis.
PMID- 28416540
TI - In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole
Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression
Models of Invasive Aspergillosis.
AB - Using an immunocompetent murine model of invasive aspergillosis (IA), we
previously reported that the efficacy of liposomal amphotericin B (L-AmB)
(Ambisome) is not hampered by the presence of azole resistance mutations in
Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P.
E. Verweij, Antimicrob Agents Chemother 57:1866-1871, 2013,
https://doi.org/10.1128/AAC.02226-12). We here investigated the role of immune
suppression, i.e., neutropenia and steroid treatment, in L-AmB efficacy in mice
infected with wild-type (WT) A. fumigatus and with azole-resistant A. fumigatus
harboring a TR34/L98H mutation in the cyp-51A gene. Survival of treated animals
at day 14 in both immunosuppressed models was significantly better than that of
nontreated controls. A dose-response relationship was observed that was
independent of the azole-resistant mechanism and the immunosuppression method
used. In the neutropenic model, 100% survival was reached at an L-AmB dose of 16
mg/kg of body weight for the WT strain and the TR34/L98H isolate. In the steroid
treated group, 90.9% survival and 100% survival were achieved for the WT isolate
and the TR34/L98H isolate with an L-AmB dose of 16 mg/kg, respectively. The 50%
effective dose (ED50) was 1.40 mg/kg (95% confidence interval [CI], 0.66 to 3.00
mg/kg) for the WT isolate and 1.92 mg/kg (95% CI, 0.60 to 6.17 mg/kg) for the
TR34/L98H isolate in the neutropenic model and was 2.40 mg/kg (95% CI, 1.93 to
2.97 mg/kg) for the WT isolate and 2.56 mg/kg (95% CI, 1.43 to 4.56 mg/kg) for
the TR34/L98H isolate in the steroid-treated group. Overall, there were no
significant differences between the two different immunosuppressed conditions in
the efficacy of L-AmB against the wild-type and azole-resistant isolates (P >
0.9). However, the required L-AmB exposure was significantly higher than that
seen in the immunocompetent model.
PMID- 28416542
TI - High-Resolution Melting Analysis for Rapid Detection of Sequence Type 131
Escherichia coli.
AB - Escherichia coli isolates belonging to the sequence type 131 (ST131) clonal
complex have been associated with the global distribution of fluoroquinolone and
beta-lactam resistance. Whole-genome sequencing and multilocus sequence typing
identify sequence type but are expensive when evaluating large numbers of
samples. This study was designed to develop a cost-effective screening tool using
high-resolution melting (HRM) analysis to differentiate ST131 from non-ST131 E.
coli in large sample populations in the absence of sequence analysis. The method
was optimized using DNA from 12 E. coli isolates. Singleplex PCR was performed
using 10 ng of DNA, Type-it HRM buffer, and multilocus sequence typing primers
and was followed by multiplex PCR. The amplicon sizes ranged from 630 to 737 bp.
Melt temperature peaks were determined by performing HRM analysis at 0.1 degrees
C resolution from 50 to 95 degrees C on a Rotor-Gene Q 5-plex HRM system.
Derivative melt curves were compared between sequence types and analyzed by
principal component analysis. A blinded study of 191 E. coli isolates of ST131
and unknown sequence types validated this methodology. This methodology returned
99.2% specificity (124 true negatives and 1 false positive) and 100% sensitivity
(66 true positives and 0 false negatives). This HRM methodology distinguishes
ST131 from non-ST131 E. coli without sequence analysis. The analysis can be
accomplished in about 3 h in any laboratory with an HRM-capable instrument and
principal component analysis software. Therefore, this assay is a fast and cost
effective alternative to sequencing-based ST131 identification.
PMID- 28416543
TI - Potential Toxicity of Polymyxins in Human Lung Epithelial Cells.
AB - Inhaled polymyxins are of considerable utility in achieving optimal exposure in
the respiratory tract for the treatment of lung infections caused by multidrug
resistant Gram-negative pathogens. Current inhaled polymyxin therapy is
empirical, and often large doses are used that may lead to potential pulmonary
adverse effects. This study aimed to investigate the effect of polymyxins on
human lung epithelial (A549) cells. The viability of A549 cells was examined
after treatment with polymyxins by flow cytometry. Activation of caspases 3, 8,
and 9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential,
and mitochondrial oxidative stress induced by polymyxin B were evaluated. The
concentration of polymyxin B required to induce 50% of maximal cell death was
1.74 mM (95% confidence interval, 1.60 to 1.90 mM). Colistin was at least 2-fold
less toxic than polymyxin B, while colistimethate was nontoxic. With 2.0 mM
polymyxin B, 30.6% +/- 11.5% (mean +/- standard deviation) of the cells were
apoptotic at 8 h and this increased to 71.3% +/- 3.72% at 24 h. Concentration-
and time-dependent activation of caspases 3, 8, and 9 was evident, while the
activation of caspase 9 was more dramatic. Furthermore, polymyxin B caused
concentration- and time-dependent FasL expression, production of mitochondrial
reactive oxygen species, and changes in mitochondrial membrane potential. This is
the first study to demonstrate that both extrinsic death receptor and intrinsic
mitochondrial pathways are involved in polymyxin-induced toxicity in A549 cells.
This knowledge base is critical for the development of novel strategies for the
safe and effective inhalation therapy of polymyxins against Gram-negative
"superbugs."
PMID- 28416544
TI - Deciphering Heteroresistance to Colistin in a Klebsiella pneumoniae Isolate from
Marseille, France.
AB - Here, we report the description of a colistin-heteroresistant Klebsiella
pneumoniae isolate fortuitously isolated from the stool sample of a patient with
suspicion of tuberculosis in a public hospital of Marseille, France. In the
colistin-resistant subpopulation, a mutation in the mgrB gene leading to a
premature stop codon was found, and the hypermucoviscous phenotype was lost.
Susceptibility to other antibiotics remained unchanged. To our knowledge, this is
the first identification of such a colistin-heteroresistant Klebsiella pneumoniae
isolate in France.
PMID- 28416545
TI - Dissemination of mcr-1-Carrying Plasmids among Colistin-Resistant Salmonella
Strains from Humans and Food-Producing Animals in Taiwan.
AB - We detected the colistin resistance gene mcr-1 in four Salmonella serovars
isolated from humans and animals with diarrhea. The resistance gene was carried
on different plasmids. One mcr-1-carrying conjugative plasmid, a variant of
pHNSHP45, was disseminated among Salmonella isolates recovered from humans, pigs,
and chickens.
PMID- 28416546
TI - Anti-influenza Activity of a Bacillus subtilis Probiotic Strain.
AB - Among Bacillus bacteria, B. subtilis is the species that produces the most
antimicrobial compounds. In this study, we analyzed the activity of probiotic
strain B. subtilis 3 against the influenza virus. The antiviral effect of this
strain has been demonstrated in vitro and in vivo A new peptide, P18, produced by
the probiotic strain was isolated, purified, chemically synthesized, and
characterized. Cytotoxicity studies demonstrated no toxic effect of P18 on Madin
Darby canine kidney (MDCK) cells, even at the highest concentration tested (100
MUg/ml). Complete inhibition of the influenza virus in vitro was observed at
concentrations of 12.5 to 100 MUg/ml. The protective effect of P18 in mice was
comparable to that of oseltamivir phosphate (Tamiflu). Further study will assess
the potential of peptide P18 as an antiviral compound and as a promising
candidate for the development of new antiviral vaccines.
PMID- 28416547
TI - Simulating Intestinal Transporter and Enzyme Activity in a Physiologically Based
Pharmacokinetic Model for Tenofovir Disoproxil Fumarate.
AB - Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir, has oral
bioavailability (25%) limited by intestinal transport (P-glycoprotein), and
intestinal degradation (carboxylesterase). However, the influence of luminal
pancreatic enzymes is not fully understood. Physiologically based pharmacokinetic
(PBPK) modeling has utility for estimating drug exposure from in vitro data. This
study aimed to develop a PBPK model that included luminal enzyme activity to
inform dose reduction strategies. TDF and tenofovir stability in porcine
pancrelipase concentrations was assessed (0, 0.48, 4.8, 48, and 480 U/ml of
lipase; 1 mM TDF; 37 degrees C; 0 to 30 min). Samples were analyzed using mass
spectrometry. TDF stability and permeation data allowed calculation of absorption
rates within a human PBPK model to predict plasma exposure following 6 days of
once-daily dosing with 300 mg of TDF. Regional absorption of drug was simulated
across gut segments. TDF was degraded by pancrelipase (half-lives of 0.07 and
0.62 h using 480 and 48 U/ml, respectively). Previously reported maximum
concentration (Cmax; 335 ng/ml), time to Cmax (Tmax; 2.4 h), area under the
concentration-time curve from 0 to 24 h (AUC0-24; 3,045 ng . h/ml), and
concentration at 24 h (C24; 48.3 ng/ml) were all within a 0.5-fold difference
from the simulated Cmax (238 ng/ml), Tmax (3 h), AUC0-24 (3,036 ng . h/ml), and
C24 (42.7 ng/ml). Simulated TDF absorption was higher in duodenum and jejunum
than in ileum (p<0.05). These data support that TDF absorption is limited by the
action of intestinal lipases. Our results suggest that bioavailability may be
improved by protection of drug from intestinal transporters and enzymes, for
example, by coadministration of enzyme-inhibiting agents or nanoformulation
strategies.
PMID- 28416548
TI - Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the
Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model.
AB - The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of
known human immunodeficiency virus type 1 (HIV-1) isolates in vitro, is a
promising candidate microbicide for preventing sexual HIV infection when
administered topically to the vagina; however, accessibility to antibody-based
prophylactic treatment by target populations in sub-Saharan Africa and other
underdeveloped regions may be limited by the high cost of conventionally produced
antibodies and the limited capacity to manufacture such antibodies. Intravaginal
rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01 (VRC01
N) over a range of release rates have been developed. The pharmacokinetics and
preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model.
The devices sustained VRC01-N release for up to 21 days at controlled rates, with
mean steady-state VRC01-N levels in vaginal fluids in the range of 102 to 103 MUg
g-1 being correlated with in vitro release rates. No adverse safety indications
were observed. These findings indicate that pod-IVRs are promising devices for
the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection
and merit further preclinical evaluation.
PMID- 28416549
TI - Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor
Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.
AB - Although genotype 4 (GT4)-infected patients represent a minor overall percentage
of the global hepatitis C virus (HCV)-infected population, the high prevalence of
the genotype in specific geographic regions coupled with substantial sequence
diversity makes it an important genotype to study for antiviral drug discovery
and development. We evaluated two direct-acting antiviral agents-grazoprevir, an
HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4
replicons prior to clinical studies in this genotype. Following a bioinformatics
analysis of available GT4 sequences, a set of replicons bearing representative
GT4 clinical isolates was generated. For grazoprevir, the 50% effective
concentration (EC50) against the replicon bearing the reference GT4a (ED43) NS3
protease and NS4A was 0.7 nM. The median EC50 for grazoprevir against chimeric
replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range,
0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A
resistance-associated substitutions was substantially overcome with the
identification of a G162R adaptive substitution in NS3. Single NS3 substitutions
D168A/V identified from de novo resistance selection studies reduced grazoprevir
antiviral activity by 137- and 47-fold, respectively, in the background of the
G162R replicon. For elbasvir, the EC50 against the replicon bearing the reference
full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC50 for elbasvir
against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM
(range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4
demonstrated a high propensity to suppress the emergence of amino acid
substitutions that confer high-potency reductions to elbasvir. Phenotypic
characterization of the NS5A amino acid substitutions identified (L30F, L30S,
M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency
losses, respectively, to elbasvir. The activity profiles of grazoprevir and
elbasvir supported the testing of the direct-acting antivirals in clinical
studies.
PMID- 28416550
TI - Identification and Optimization of Thienopyridine Carboxamides as Inhibitors of
HIV Regulatory Complexes.
AB - Viral regulatory complexes perform critical functions during virus replication
and are important targets for therapeutic intervention. In HIV, the Tat and Rev
proteins form complexes with multiple viral and cellular factors to direct
transcription and export of the viral RNA. These complexes are composed of many
proteins and are dynamic, making them difficult to fully recapitulate in vitro
Therefore, we developed a cell-based reporter assay to monitor the assembly of
viral complexes for inhibitor screening. We screened a small-molecule library and
identified multiple hits that inhibit the activity of the viral complexes. A
subsequent chemistry effort was focused on a thieno[2,3-b]pyridine scaffold,
examples of which inhibited HIV replication and the emergence from viral latency.
Notable aspects of the effort to determine the structure-activity relationship
(SAR) include migration to the regioisomeric thieno[2,3-c]pyridine ring system
and the identification of analogs with single-digit nanomolar activity in both
reporter and HIV infectivity assays, an improvement of >100-fold in potency over
the original hits. These results validate the screening strategy employed and
reveal a promising lead series for the development of a new class of HIV
therapeutics.
PMID- 28416551
TI - Comparative Pharmacodynamics of Telavancin and Vancomycin in the Neutropenic
Murine Thigh and Lung Infection Models against Staphylococcus aureus.
AB - The pharmacodynamics of telavancin and vancomycin were compared using neutropenic
murine thigh and lung infection models. Four Staphylococcus aureus strains were
included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the
vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of
escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and
vancomycin were linear over the dose range. Epithelial lining fluid (ELF)
pharmacokinetics for each drug revealed that penetration into the ELF mirrored
the percentage of the free fraction (the fraction not protein bound) in plasma
for each drug. Telavancin (0.3125 to 80 mg/kg/6 h) and vancomycin (0.3125 to
1,280 mg/kg/6 h) were administered by the subcutaneous route in treatment
studies. Dose-dependent bactericidal activity against all four strains was
observed in both models. A sigmoid maximum-effect model was used to determine the
area under the concentration-time curve (AUC)/MIC exposure associated with net
stasis and 1-log10 kill relative to the burden at the start of therapy. The 24-h
plasma free drug AUC (fAUC)/MIC values associated with stasis and 1-log kill were
remarkably congruent. Net stasis for telavancin was noted at fAUC/MIC values of
83 and 40.4 in the thigh and lung, respectively, and 1-log kill was noted at
fAUC/MIC values of 215 and 76.4, respectively. For vancomycin, the fAUC/MIC
values for stasis were 77.9 and 45.3, respectively, and those for 1-log kill were
282 and 113, respectively. The 24-h ELF total drug AUC/MIC targets in the lung
model were very similar to the 24-h plasma free drug AUC/MIC targets for each
drug. Integration of human pharmacokinetic data for telavancin, the results of
the MIC distribution studies, and the pharmacodynamic targets identified in this
study suggests that the current dosing regimen of telavancin is optimized to
obtain drug exposures sufficient to treat S. aureus infections.
PMID- 28416552
TI - In Vivo Pharmacodynamic Target Assessment of Eravacycline against Escherichia
coli in a Murine Thigh Infection Model.
AB - Eravacycline is a novel fluorocycline antibiotic with potent activity against a
broad range of pathogens, including strains with tetracycline and other drug
resistance phenotypes. The goal of the studies was to determine which
pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated
with efficacy in the murine thigh infection model. Six Escherichia coli isolates
were utilized for the studies. MICs were determined using CLSI methods and ranged
from 0.125 to 0.25 mg/liter. A neutropenic murine thigh infection model was
utilized for all treatment studies. Single-dose plasma pharmacokinetics were
determined in mice after administration of 2.5, 5, 10, 20, 40, and 80 mg/kg of
body weight. Pharmacokinetic studies exhibited maximum plasma concentration
(Cmax) values of 0.34 to 2.58 mg/liter, area under the concentration-time curve
(AUC) from time zero to infinity (AUC0-infinity) values of 2.44 to 57.6 mg .
h/liter, and elimination half-lives of 3.9 to 17.6 h. Dose fractionation studies
were performed using total drug doses of 6.25 mg/kg to 100 mg/kg fractionated
into 6-, 8-, 12-, or 24-h regimens. Nonlinear regression analysis demonstrated
that the 24-h free drug AUC/MIC (fAUC/MIC) was the PK/PD parameter that best
correlated with efficacy (R2 = 0.80). In subsequent studies, we used the
neutropenic murine thigh infection model to determine if the magnitude of the
AUC/MIC needed for the efficacy of eravacycline varied among pathogens. Mice were
treated with 2-fold increasing doses (range, 3.125 to 50 mg/kg) of eravacycline
every 12 h. The mean fAUC/MIC magnitudes associated with the net stasis and the 1
log-kill endpoints were 27.97 +/- 8.29 and 32.60 +/- 10.85, respectively.
PMID- 28416553
TI - Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically
Ill Patient on Continuous Venovenous Hemofiltration.
AB - Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat
multidrug-resistant Pseudomonas aeruginosa bacteremia in a critically ill patient
on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug
concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8
h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6.
Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively,
were as follows: maximum plasma concentration (Cmax), 61.10 and 14.54 mg/liter;
minimum plasma concentration (Cmin), 31.96 and 8.45 mg/liter; half-life (t1/2),
6.07 and 6.78 h; apparent volume of distribution at the steady state (Vss), 27.23
and 30.81 liters; total clearance at the steady state (CLss), 2.87 and 2.95
liters/h; area under the concentration-time curve from 0 to 8 h (AUC0-8), 347.87
and 85.69 mg . h/liter. Concentrations of ceftazidime in plasma exceeded the
ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean
CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%,
respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The
calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for
avibactam was 1.59 liters/h, representing 57.1% of the total clearance of
ceftazidime and 54.3% of the total clearance of avibactam. Further data that
include multiple patients and dialysis modes are needed to verify the optimal
ceftazidime-avibactam dosing strategy during critical illness and CVVH.
PMID- 28416554
TI - In Vitro Study of ISApl1-Mediated Mobilization of the Colistin Resistance Gene
mcr-1.
AB - The plasmid-mediated mcr-1 gene encodes a phosphoethanolamine transferase that
confers resistance to polymyxins. The mcr-1 gene is associated with insertion
sequence ISApl1 (IS30 family). In vitro mobilization assays demonstrated the
functionality of the composite transposon structure ISApl1-mcr-1-ISApl1
Transposition generated a 2-bp duplication and occurred in AT-rich DNA regions.
This is the first report demonstrating the mobility of the mcr-1 gene by
transposition.
PMID- 28416555
TI - Mycobacterium tuberculosis Proteome Response to Antituberculosis Compounds
Reveals Metabolic "Escape" Pathways That Prolong Bacterial Survival.
AB - Tuberculosis (TB) continues to be one of the most common bacterial infectious
diseases and is the leading cause of death in many parts of the world. A major
limitation of TB therapy is slow killing of the infecting organism, increasing
the risk for the development of a tolerance phenotype and drug resistance.
Studies indicate that Mycobacterium tuberculosis takes several days to be killed
upon treatment with lethal concentrations of antibiotics both in vitro and in
vivo To investigate how metabolic remodeling can enable transient bacterial
survival during exposure to bactericidal concentrations of compounds, M.
tuberculosis strain H37Rv was exposed to twice the MIC of isoniazid, rifampin,
moxifloxacin, mefloquine, or bedaquiline for 24 h, 48 h, 4 days, and 6 days, and
the bacterial proteomic response was analyzed using quantitative shotgun mass
spectrometry. Numerous sets of de novo bacterial proteins were identified over
the 6-day treatment. Network analysis and comparisons between the drug treatment
groups revealed several shared sets of predominant proteins and enzymes
simultaneously belonging to a number of diverse pathways. Overexpression of some
of these proteins in the nonpathogenic Mycobacterium smegmatis extended bacterial
survival upon exposure to bactericidal concentrations of antimicrobials, and
inactivation of some proteins in M. tuberculosis prevented the pathogen from
escaping the fast killing in vitro and in macrophages, as well. Our biology
driven approach identified promising bacterial metabolic pathways and enzymes
that might be targeted by novel drugs to reduce the length of tuberculosis
therapy.
PMID- 28416556
TI - Colistin-Resistant mcr-1-Positive Escherichia coli on Public Beaches, an
Infectious Threat Emerging in Recreational Waters.
AB - The emergence and rapid spread of colistin-resistant Escherichia coli carrying
the mcr-1 gene have generated an urgent need to strengthen surveillance. We
performed a meticulous investigation of strains of this sort, which resulted in
the identification of international clones of E. coli carrying IncX4-plasmid
mediated mcr-1 and blaCTX-M genes in recreational waters of public urban beaches
in cities with high tourist turnover, highlighting a new environmental reservoir.
PMID- 28416557
TI - Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point
Mutations in the Squalene Epoxidase Gene.
AB - Terbinafine is one of the allylamine antifungal agents whose target is squalene
epoxidase (SQLE). This agent has been extensively used in the therapy of
dermatophyte infections. The incidence of patients with tinea pedis or unguium
tolerant to terbinafine treatment prompted us to screen the terbinafine
resistance of all Trichophyton clinical isolates from the laboratory of the
Centre Hospitalier Universitaire Vaudois collected over a 3-year period and to
identify their mechanism of resistance. Among 2,056 tested isolates, 17 (~1%)
showed reduced terbinafine susceptibility, and all of these were found to harbor
SQLE gene alleles with different single point mutations, leading to single amino
acid substitutions at one of four positions (Leu393, Phe397, Phe415, and His440)
of the SQLE protein. Point mutations leading to the corresponding amino acid
substitutions were introduced into the endogenous SQLE gene of a terbinafine
sensitive Arthroderma vanbreuseghemii (formerly Trichophyton mentagrophytes)
strain. All of the generated A. vanbreuseghemii transformants expressing mutated
SQLE proteins exhibited obvious terbinafine-resistant phenotypes compared to the
phenotypes of the parent strain and of transformants expressing wild-type SQLE
proteins. Nearly identical phenotypes were also observed in A. vanbreuseghemii
transformants expressing mutant forms of Trichophyton rubrum SQLE proteins.
Considering that the genome size of dermatophytes is about 22 Mb, the frequency
of terbinafine-resistant clinical isolates was strikingly high. Increased
exposure to antifungal drugs could favor the generation of resistant strains.
PMID- 28416558
TI - In Vitro Discordance with In Vivo Activity: Humanized Exposures of Ceftazidime
Avibactam, Aztreonam, and Tigecycline Alone and in Combination against New Delhi
Metallo-beta-Lactamase-Producing Klebsiella pneumoniae in a Murine Lung Infection
Model.
AB - The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)
producing bacteria remains clinically challenging given the multidrug resistant
(MDR) phenotype associated with these bacteria. Despite resistance in vitro,
ceftazidime-avibactam previously demonstrated in vivo activity against NDM
positive Enterobacteriaceae Herein, we observed in vitro synergy with ceftazidime
avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In
vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10
CFU bacterial reduction; therefore, no in vivo synergy was observed.
PMID- 28416560
TI - Horizontal schools-based health programme in rural Kenya.
AB - BACKGROUND: Primary school children in low-income countries are at risk of many
diseases and poor health affects attendance, cognition and ability to learn.
Developing school health and nutrition strategies has been extensively
highlighted as a global priority, with a particular focus on complex programme
design. However, such programmes are relatively untested in low-income settings.
METHOD: We implemented a complex school health and nutrition programme in two
schools in Western Kenya over 3 years. There were numerous elements covering
health policy, skills-based health education, infrastructure and disease
prevention. A local non-governmental organisation, with involvement from local
government and the community, performed programme implementation. Height-for-age,
weight-for-age,height-for-weight, anaemia prevalence, academic performance and
school attendance were the primary outcome measures. RESULTS: The programme
improved nutrition, academic performance and anaemia prevalence. The number of
underweight children fell from 20% to 11% (OR 0.51 95% CI 0.39 to 0.68 p=<0.01)
and stunting prevalence fell from 29.9% to 20% (OR 0.59 95% CI 0.50 to 0.68
p=<0.01). Academic performance improved with a 74% reduction in odds of failing
assessments (OR 0.26 95% CI 0.22 to 0.29 p=<0.01). Anaemia prevalence fell from
17.2% to 11%. The programme showed an increase in low body mass index prevalence
and no effect on school attendance, the reasons for which are unclear.
DISCUSSION: These results are encouraging and demonstrate that complex schools
health programmes can lead to positive gains in health, nutrition and importantly
academic performance. There is a need for further evaluation of comprehensive
school health interventions in poor communities.
PMID- 28416559
TI - A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention
of Intraluminal Central Venous Catheter Infections in Cancer Patients.
AB - For long-term central lines (CL), the lumen is the major source of central line
associated bloodstream infections (CLABSI). The current standard of care for
maintaining catheter patency includes flushing the CL with saline or heparin.
Neither agent has any antimicrobial activity. Furthermore, heparin may enhance
staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel
nonantibiotic catheter lock solution for the prevention of CLABSI. Between
November 2015 and February 2016, we enrolled 60 patients with hematologic
malignancies who had peripherally inserted central catheters (PICC) to receive
the study lock solution. The study lock consisted of 15 or 30 MUg/ml of
nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen
was locked for at least 2 h once daily prior to being flushed. After enrollment
of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the
dose was escalated to the higher dose (30 MUg/ml). There were no serious related
adverse events or episodes of hypotension with lock administration. Two patients
experienced mild transient adverse events (one headache and one rash) possibly
related to the lock and that resolved without residual effect. The CLABSI rate
was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis,
compared with a rate of 1.9/1,000 CD at the institution in the same patient
population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and
well tolerated. It may prevent CLABSI when given daily to cancer patients. Large,
prospective, randomized clinical trials are needed to validate these findings.
(This study has been registered at ClinicalTrials.gov under identifier
NCT02577718.).
PMID- 28416561
TI - Requirements for and current provision of rehabilitation services for children
after severe acquired brain injury in the UK: a population-based study.
AB - OBJECTIVES: Survival with brain injury is an outcome of severe illness that may
be becoming more common. Provision for children in this situation has received
little attention. We sought to estimate rates of severe paediatric acquired brain
injury (ABI) requiring rehabilitation and to describe current provision of
services for these children in the UK. METHODS: This study conducted an analysis
of Hospital Episode Statistics data between April 2003 and March 2012,
supplemented by a UK provider survey completed in 2015. A probable severe ABI
requiring rehabilitation (PSABIR) event was inferred from the co-occurrence of a
medical condition likely to cause ABI (such as meningitis) and a prolonged
inpatient stay (>=28 days). RESULTS: During the period studied, 4508 children
aged 1-18 years in England had PSABIRs. Trauma was the most common cause (30%)
followed by brain tumours (19%) and anoxia (18.3%). An excess in older males was
attributable to trauma. We estimate the incidence of PSABIR to be at least 2.93
(95%CI 2.62 to 3.26) per 100 000 young people (1-18 years) pa. The provider
survey confirmed marked geographic variability in the organisation of services in
the UK. CONCLUSIONS: There are at least 350 PSABIR events in children in the UK
annually, a health problem of similar magnitude to that of cerebral palsy.
Service provision for this population varies widely around the UK, in contrast
with the nationally coordinated approach to paediatric intensive care and major
trauma provision.
PMID- 28416562
TI - Henry Head, herpes zoster and the graphic development of his 'scheme of the
dermatomes in man'.
PMID- 28416563
TI - Home-based therapy for chronic Wernicke's aphasia.
PMID- 28416564
TI - The London Contribution to Neurology and Psychiatry: The second British Symposium
on the History of Neurology and Psychiatry.
PMID- 28416565
TI - Cingulo-insular structural alterations associated with psychogenic symptoms,
childhood abuse and PTSD in functional neurological disorders.
AB - OBJECTIVE: Adverse early-life events are predisposing factors for functional
neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo
insular regions are implicated in the biology of both conditions and are sites of
stress-mediated neuroplasticity. We hypothesised that functional neurological
symptoms and the magnitude of childhood abuse would be associated with
overlapping anterior cingulate cortex (ACC) and insular volumetric reductions,
and that FND and PTSD symptoms would map onto distinct cingulo-insular areas.
METHODS: This within-group voxel-based morphometry study probes volumetric
associations with self-report measures of functional neurological symptoms,
adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate
secondary analyses were also performed in the subset of 18 women with FND to
account for gender-specific effects. RESULTS: Across the entire cohort, there
were no statistically significant volumetric associations with self-report
measures of functional neurological symptom severity or childhood abuse. In women
with FND, however, parallel inverse associations were observed between left
anterior insular volume and functional neurological symptoms as measured by the
Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms
Conversion Disorder subscale. Similar inverse relationships were also appreciated
between childhood abuse burden and left anterior insular volume. Across all
subjects, PTSD symptom severity was inversely associated with dorsal ACC volume,
and the magnitude of lifetime adverse events was inversely associated with left
hippocampal volume. CONCLUSIONS: This study reveals distinct cingulo-insular
alterations for FND and PTSD symptoms and may advance our understanding of FND.
Potential biological convergence between stress-related neuroplasticity,
functional neurological symptoms and reduced insular volume was identified.
PMID- 28416566
TI - Structure of the DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of
hairpins and motif Va in translocation along RNA.
AB - Three families of nucleic acid-dependent ATPases (DEAH/RHA, Ski2-like, and
NS3/NPH-II), termed the DExH ATPases, are thought to execute myriad functions by
processive, ATP-dependent, 3' to 5' translocation along single-stranded nucleic
acid. While the mechanism of translocation of the viral NS3/NPH-II family has
been studied extensively, it has not been clear if or how the principles that
have emerged for this family extend to the other two families. Here we report the
crystal structure of the yeast DEAH/RHA family ATPase Prp43p, which functions in
splicing and ribosome biogenesis, in complex with poly-uracil and a
nonhydrolyzable ATP analog. The structure reveals a conserved DEAH/RHA-specific
variation of motif Ib within the RecA1 domain of the catalytic core, in which the
motif elongates as a beta-hairpin that bookends the 3' end of a central RNA
stack, a function that in the viral and Ski-2 families is performed by an
auxiliary domain. Supporting a fundamental role in translocation, mutations in
this hairpin abolished helicase activity without affecting RNA binding or ATPase
activity. While the structure reveals differences with viral ATPases in the RecA1
domain, our structure demonstrates striking similarities with viral ATPases in
the RecA2 domain of the catalytic core, including both a prominent beta-hairpin
that bookends the 5' end of the RNA stack and a dynamic motif Va that is
implicated in mediating translocation. Our crystal structure, genetic, and
biochemical experiments, as well as comparisons with other DExH ATPases, support
a generalized mechanism for the DExH class of helicases involving a pair of
bookends that inchworm along RNA.
PMID- 28416567
TI - The C-terminal dsRNA-binding domain of Drosophila Dicer-2 is crucial for
efficient and high-fidelity production of siRNA and loading of siRNA to
Argonaute2.
AB - Drosophila Dicer-2 efficiently and precisely produces 21-nucleotide (nt) siRNAs
from long double-stranded RNA (dsRNA) substrates and loads these siRNAs onto the
effector protein Argonaute2 for RNA silencing. The functional roles of each
domain of the multidomain Dicer-2 enzyme in the production and loading of siRNAs
are not fully understood. Here we characterized Dicer-2 mutants lacking either
the N-terminal helicase domain or the C-terminal dsRNA-binding domain (CdsRBD)
(DeltaHelicase and DeltaCdsRBD, respectively) in vivo and in vitro. We found that
DeltaCdsRBD Dicer-2 produces siRNAs with lowered efficiency and length fidelity,
producing a smaller ratio of 21-nt siRNAs and higher ratios of 20- and 22-nt
siRNAs in vivo and in vitro. We also found that DeltaCdsRBD Dicer-2 cannot load
siRNA duplexes to Argonaute2 in vitro. Consistent with these findings, we found
that DeltaCdsRBD Dicer-2 causes partial loss of RNA silencing activity in vivo.
Thus, Dicer-2 CdsRBD is crucial for the efficiency and length fidelity in siRNA
production and for siRNA loading. Together with our previously published
findings, we propose that CdsRBD binds the proximal body region of a long dsRNA
substrate whose 5'-monophosphate end is anchored by the phosphate-binding pocket
in the PAZ domain. CdsRBD aligns the RNA to the RNA cleavage active site in the
RNase III domain for efficient and high-fidelity siRNA production. This study
reveals multifunctions of Dicer-2 CdsRBD and sheds light on the molecular
mechanism by which Dicer-2 produces 21-nt siRNAs with a high efficiency and
fidelity for efficient RNA silencing.
PMID- 28416569
TI - Association between smoking and health outcomes in an economically deprived
population: the Liverpool Lung Project.
AB - BACKGROUND: The association between smoking and several health outcomes among
those from the most deprived communities in the UK has not previously been
detailed. The aim of this study is to examine the impact of smoking on health
outcomes specifically among a particularly deprived population in a developed
country (Liverpool; one of the most deprived local authorities in England).
METHODS: The Liverpool Lung Project recruited a prospective cohort of 8753
participants from across Liverpool, aged 45-79 years between 1998 and 2008.
Participants were followed annually through the Hospital Episode Statistics until
31 January 2013. Logistic regression models were used to identify health outcomes
of smoking. RESULTS: From our study population, 5195 were smokers and 3558 were
non-smokers. Smoking was associated with male gender (OR 1.62, 95% CI 1.48 to
1.77), pneumonia (1.28, 95% CI 1.10 to 1.49), chronic obstructive pulmonary
disease (1.30, 95% CI 1.14 to 1.48), emphysema (5.46, 95% CI 3.48 to 8.55),
bronchitis (1.85, 95% CI 1.65 to 2.07), other cancers (1.69, 95% CI 1.44 to
1.99), lung cancer (6.0, 95% CI 3.72 to 9.69), diabetes (1.21, 95% CI 1.02 to
1.43) and cardiovascular disease (1.45, 95% CI 1.25 to 1.67). CONCLUSIONS:
Smokers from deprived backgrounds in Liverpool showed increased risk of
developing pneumonia, emphysema, chronic obstructive pulmonary disease,
bronchitis, lung cancer, other types of cancer, cardiovascular disease and
diabetes. These findings are in line with the literature and may help to inform
public health policies and ultimately work towards addressing smoking-related
health inequalities.
PMID- 28416568
TI - Pharmacological and Toxicological Properties of the Potent Oral gamma-Secretase
Modulator BPN-15606.
AB - Alzheimer's disease (AD) is characterized neuropathologically by an abundance of
1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid
amyloid-beta peptide (Abeta), as well as 2) neurofibrillary tangles composed of
aggregates of hyperphosporylated tau. Elevations in the concentrations of the
Abeta42 peptide in the brain, as a result of either increased production or
decreased clearance, are postulated to initiate and drive the AD pathologic
process. We initially introduced a novel class of bridged aromatics referred
tgamma-secretase modulatoro as gamma-secretase modulators that inhibited the
production of the Abeta42 peptide and to a lesser degree the Abeta40 peptide
while concomitantly increasing the production of the carboxyl-truncated Abeta38
and Abeta37 peptides. These modulators potently lower Abeta42 levels without
inhibiting the gamma-secretase-mediated proteolysis of Notch or causing
accumulation of carboxyl-terminal fragments of APP. In this study, we report a
large number of pharmacological studies and early assessment of toxicology
characterizing a highly potent gamma-secretase modulator (GSM), (S)-N-(1-(4
fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4
methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to
significantly lower Abeta42 levels in the central nervous system of rats and mice
at doses as low as 5-10 mg/kg, significantly reduce Abeta neuritic plaque load in
an AD transgenic mouse model, and significantly reduce levels of insoluble
Abeta42 and pThr181 tau in a three-dimensional human neural cell culture model.
Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose
toxicity studies in nonhuman primates have designated this GSM for 28-day
Investigational New Drug-enabling good laboratory practice studies and positioned
it as a candidate for human clinical trials.
PMID- 28416570
TI - Taking health into account in all policies: raising and keeping health equity
high on the political agenda.
PMID- 28416571
TI - Negative wealth shock and short-term changes in depressive symptoms and
medication adherence among late middle-aged adults.
AB - BACKGROUND: Experiencing a negative wealth shock in late middle age may cause
high levels of stress and induce reductions in health-related consumption.
METHODS: We used data on late middle age individuals (51-64 years) from the
longitudinal US-based Health and Retirement Study (N=19 281) to examine the
relationship between negative wealth shock and short-term outcomes that serve as
markers of the pathways from wealth shock to health: elevated depressive
symptoms, as a marker of the stress pathway and cost-related medication non
adherence (CRN), as a marker of the consumption pathway. Negative wealth shock
was considered to be a loss of total net worth of 75% or more. RESULTS: Using a
nested cross-over approach-a within-person design among exposed individuals only
that adjusts by design for all time-invariant individual characteristics-we found
that negative wealth shock was significantly associated with increased odds of
elevated depressive symptoms (OR=1.50, CI 1.10 to 2.05), but was not
significantly associated with higher odds of CRN (OR=1.18, CI 0.76 to 1.82), even
after further adjustment for time-varying sociodemographic and health covariates.
CONCLUSIONS: Negative wealth shock during late middle age confers an increased
risk of elevated depressive symptoms, but does not change levels of CRN. Personal
and policy factors that may buffer the mental health risks of negative wealth
shock, such as social support and social welfare policy, should be considered.
PMID- 28416572
TI - Alternatives assessment: new ideas, frameworks and policies.
PMID- 28416573
TI - Changes in directly alcohol-attributable mortality during the great recession by
employment status in Spain: a population cohort of 22 million people.
AB - BACKGROUND: Macroeconomic fluctuations can impact differentially on alcohol
related problems across sociodemographic groups. We assess trend changes in
directly alcohol-attributable (DAA) mortality in the population aged 25-64 during
the post-2008 recession in Spain according to employment status and other
sociodemographic factors. METHODS: Nationwide cohort study covering 21.9 million
people living in Spain in 2001. People were classified by employment status and
other factors. The annual percentage change (APC) in mortality rates during 2002
2007 (precrisis) and 2008-2011 (crisis) was estimated by the Poisson regression.
The period effect size was then calculated as the difference between crisis and
precrisis APCs. RESULTS: The age-adjusted APCs in DAA mortality were 6.9% in 2002
2007 and 3.7% in 2008-2011 among employed people, and -4.3% and -0.4%,
respectively, among non-employed people. Statistically significant trend changes
in such mortality during the crisis were found, which were favourable in certain
employed subgroups (manual workers and employees aged 25-49), and unfavourable in
the total non-employed population and certain non-employed subgroups (men, non
married and especially medium/high-wealth people). The greatest unfavourable
change corresponded to non-employed people living in households of 72-104 m2 who
had 2 or more cars. Favourable changes were also found in the remaining employed
subgroups, especially women and non-married people, although they did not reach
statistical significance. CONCLUSIONS: Our findings suggest that the post-2008
Spanish crisis had a heterogeneous impact across sociodemographic subgroups on
DAA mortality, and that employment status seemed to have an important effect. The
impact was especially unfavourable on the non-employed, particularly those with
substantial material wealth.
PMID- 28416575
TI - Moving Closer To Victory.
PMID- 28416574
TI - A Glutamate-Substituted Mutant Mimics the Phosphorylated and Active Form of
Guanylyl Cyclase-A.
AB - Multisite phosphorylation is required for activation of guanylyl cyclase (GC)-A,
also known as NPR-A or NPR1, by cardiac natriuretic peptides (NPs). Seven
chemically identified sites (Ser-487, Ser-497, Thr-500, Ser-502, Ser-506, Ser
510, and Thr-513) and one functionally identified putative site (Ser-473) were
reported. Single alanine substitutions for Ser-497, Thr-500, Ser-502, Ser-506,
and Ser-510 reduced maximal velocity (Vmax), whereas glutamate substitutions had
no effect or increased Vmax Ala but not Glu substitution for Ser-497 increased
the Michaelis constant (Km) approximately 400%. A GC-A mutant containing Glu
substitutions for all seven chemically identified sites (GC-A-7E) had a Km
approximately 10-fold higher than phosphorylated wild-type (WT) GC-A, but one
additional substitution for Ser-473 to make GC-A-8E resulted in the same Vmax,
Km, and EC50 as the phosphorylated WT enzyme. Adding more glutamates to make GC-A
9E or GC-A-10E had little effect on activity, and sequential deletion of
individual glutamates in GC-A-8E progressively increased the Km Double Ala
substitutions for Ser-497 and either Thr-500, Ser-510 or Thr-513 in WT-GC-A
increased the Km 23- to 70-fold but the same mutations in GC-A-8E only increased
the Km 8-fold, consistent with one site affecting the phosphorylation of other
sites. Phosphate measurements confirmed that single-site Ala substitutions
reduced receptor phosphate levels more than expected for the loss of a single
site. We conclude that a concentrated region of negative charge, not steric
properties, resulting from multiple interdependent phosphorylation sites is
required for a GC-A conformation capable of transmitting the hormone binding
signal to the catalytic domain.
PMID- 28416576
TI - Pathways Involved in Formation of Mammary Organoid Architecture Have Keys to
Understanding Drug Resistance and to Discovery of Druggable Targets.
AB - Signals from the extracellular matrix (ECM) are received at the cell surface
receptor, transmitted to the cytoskeletons, and transferred to the nucleus and
chromatin for tissue- and context-specific gene expression. Cells, in return,
modulate the cell shape and ECM, allowing for the maintenance of tissue
homeostasis as well as for coevolution and adaptation to the environmental
signals. We postulated the existence of dynamic and reciprocal interactions
between the ECM and the nucleus more than three decades ago, but now these
pathways have been proven experimentally thanks to the advances in imaging and
cell/molecular biology techniques. In this review, we will introduce some of our
recent work that has validated the critical roles of the three-dimensional (3D)
tissue architecture in determining mammary biology, therapeutic response, and
druggable targets. We describe a novel screen based on reversion of the malignant
phenotype in 3D assays. We will also summarize our recent discoveries of the
integration of feedback signaling for mammary acinar formation and phenotypic
reversion of tumor cells in the LrECM. Lastly, we will introduce our exciting
discovery of the physical linkages between the cell surface and cytofibers within
a tunnel deep inside of the nucleus, enabling interaction with nuclear lamin and
SUN proteins.
PMID- 28416578
TI - WITHDRAWN: Quantitative mass spectrometry analysis of PD-L1 protein expression, N
glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma.
AB - This article has been withdrawn by the authors. We discovered an error after this
manuscript was published as a Paper in Press. Specifically, we learned that the
structures of glycans presented for the PD-L1 peptide were drawn and labeled
incorrectly. We wish to withdraw this article and submit a corrected version for
review.
PMID- 28416577
TI - Normal and Neoplastic Stem Cells.
AB - A stem cell is broadly defined as a cell that retains the capacity to self-renew,
a feature that confers the ability to continuously make identical daughter cells
or additional cells that will differentiate into downstream progeny. This highly
regulated genetic program to retain "stemness" is under active investigation.
Research in our laboratory has explored similarities and differences in
embryonic, tissue-specific, and neoplastic stem cells and their terminally
differentiated counterparts. In this review, we will focus on the contributions
of our laboratory, in particular on the studies that identified the mouse
hematopoietic stem cell (HSC) and the human leukemic stem cell. These studies
have led to significant improvements in both preclinical and clinical research,
including improved clinical bone marrow transplantation protocols, isolation of
nonleukemic HSCs, a cancer immunotherapy currently in clinical trials, and
development of a HSC reporter mouse. These studies and the current follow-up
research by us and others will continue to identify the properties, function, and
regulation of both normal and neoplastic stem cells.
PMID- 28416579
TI - Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of
phospholipids containing unsaturated long (>=C20)-acyl chains in macrophages.
AB - Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl
CoAs to FFAs. ACOT7 is induced by lipopolysaccharide (LPS); thus, we investigated
downstream effects of LPS-induced induction of ACOT7 and its role in inflammatory
settings in myeloid cells. Enzymatic thioesterase activity assays in WT and ACOT7
deficient macrophage lysates indicated that endogenous ACOT7 contributes a
significant fraction of total acyl-CoA thioesterase activity toward C20:4-, C20:5
, and C22:6-CoA, but contributes little activity toward shorter acyl-CoA species.
Lipidomic analyses revealed that LPS causes a dramatic increase, primarily in
bis(monoacylglycero)phosphate species containing long (>=C20) polyunsaturated
acyl-chains in macrophages, and that the limited effect observed by ACOT7
deficiency is restricted to glycerophospholipids containing 20-carbon unsaturated
acyl-chains. Furthermore, ACOT7 deficiency did not detectably alter the ability
of LPS to induce cytokines or prostaglandin E2 production in macrophages.
Consistently, although ACOT7 was induced in macrophages from diabetic mice,
hematopoietic ACOT7 deficiency did not alter the stimulatory effect of diabetes
on systemic inflammation or atherosclerosis in LDL receptor-deficient mice. Thus,
inflammatory stimuli induce ACOT7 and remodeling of phospholipids containing
unsaturated long (>=C20)-acyl chains in macrophages, and, although ACOT7 has
preferential thioesterase activity toward these lipid species, loss of ACOT7 has
no major detrimental effect on macrophage inflammatory phenotypes.>=.
PMID- 28416580
TI - A TSPO ligand attenuates brain injury after intracerebral hemorrhage.
AB - Intracerebral hemorrhage (ICH) is a devastating disease without effective
treatment. After ICH, the immediate infiltration of leukocytes and activation of
microglia are accompanied by a rapid up-regulation of the 18-kDa translocator
protein (TSPO). TSPO ligands have shown anti-inflammatory and neuroprotective
properties in models of CNS injury. In this study, we determined the impact of a
TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of
ICH. TSPO was up-regulated in Iba1+ cells from brains of patients with ICH and in
CD11b+CD45int cells from mice subjected to collagenase-induced ICH. Etifoxine
significantly reduced neurodeficits and perihematomal brain edema after ICH
induction by injection of either autologous blood or collagenase. In collagenase
induced ICH mice, the protection of etifoxine was associated with reduced
leukocyte infiltration into the brain and microglial production of IL-6 and TNF
alpha. Etifoxine improved blood-brain barrier integrity and diminished cell
death. Notably, the protective effect of etifoxine was abolished in mice depleted
of microglia by using a colony-stimulating factor 1 receptor inhibitor. These
results indicate that the TSPO ligand etifoxine attenuates brain injury and
inflammation after ICH. TSPO may be a viable therapeutic target that requires
further investigations in ICH.-Li, M., Ren, H., Sheth, K. N., Shi, F.-D., Liu, Q.
A TSPO ligand attenuates brain injury after intracerebral hemorrhage.
PMID- 28416582
TI - Relationship between oxygen concentration and temperature in an exothermic
warming device.
AB - INTRODUCTION: Actively warming hypothermic patients or preventing hypothermia is
critical in optimising outcomes in patients with traumatic injuries. Our aim was
to investigate the effect of ambient oxygen concentration on the rate and change
in temperature of the TechTrade Ready-Heat II exothermic (oxygen-activated)
warming blanket, to evaluate safety and ascertain the risk of thermal injury.
METHODS: A mannequin covered with an exothermic blanket was placed in a sealed
oxygen tent. An ambulance blanket was placed between the TechTrade Ready-Heat II
exothermic blanket and the mannequin. Two temperature probes were placed directly
on the surface of the mannequin; one on the torso away from the heating packs and
the other directly beneath the exothermic heating pack. The mannequin was exposed
to increasing oxygen concentrations at 10% increments, starting at 21%. The
experiment was conducted nine times, each time using a new blanket. Maximum
temperature of the mannequin 'skin' and rate of rise were recorded from both
temperature sensors. RESULTS: In room air (21% oxygen), the mannequin surface
reached 52 degrees C after 60 min, matching manufacturer specifications. At 30%
oxygen concentration, the temperature directly beneath the exothermic heating
pack exceeded the 65 degrees C threshold at which rapid thermal burns occur,
reaching 72.5 degrees C, with minimal change in overall torso temperature.
CONCLUSION: The supplemental use of oxygen in patients with traumatic injuries
that increases ambient oxygen levels in the presence of exothermic warming
devices may represent a significant risk to the patient. We suggest that
prehospital care providers remain highly vigilant of heat when using high-flow
oxygen and the subsequent fire risk, while manufacturers of exothermic blankets
should consider ways to improve safety.
PMID- 28416581
TI - TRP channels in brown and white adipogenesis from human progenitors: new
therapeutic targets and the caveats associated with the common antibiotic,
streptomycin.
AB - Transient receptor potential (TRP) channels are polymodal cell sensors responding
to diverse stimuli and widely implicated in the developmental programs of
numerous tissues. The evidence for an involvement of TRP family members in
adipogenesis, however, is scant. We present the first comprehensive expression
profile of all known 27 human TRP genes in mesenchymal progenitors cells during
white or brown adipogenesis. Using positive trilineage differentiation as an
exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to
be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the
brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator
activated receptor gamma coactivator (PGC)-1alpha as well as attenuated forskolin
stimulated uncoupled respiration. However, indices of generalized adipogenesis,
such as lipid droplet morphology and fatty acid binding protein (FAPB)-4
expression, were not affected, indicating a principal mitochondrial role of
TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression
and augmented uncoupled respiration predominantly in white adipocytes (browning),
whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP
1 expression, and mitigated uncoupled respiration; menthol was less capable of
augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and
TRPM8 hence appear to be involved in the priming of mitochondria to perform
uncoupled respiration downstream of adenylate cyclase. Our results also
underscore the developmental caveats of using antibiotics in adipogenic studies.
Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A.,
Shabbir, A., Franco-Obregon, A., Raghunath, M. TRP channels in brown and white
adipogenesis from human progenitors: new therapeutic targets and the caveats
associated with the common antibiotic, streptomycin.
PMID- 28416583
TI - Physiological and Pathological Roles in Human Adrenal of the Glomeruli-Defining
Matrix Protein NPNT (Nephronectin).
AB - Primary aldosteronism is a common cause of hypertension, which becomes refractory
if undiagnosed, but potentially curable when caused by an aldosterone-producing
adenoma (APA). The discovery of somatic mutations and differences in clinical
presentations led to recognition of small but common zona glomerulosa (ZG)-like
adenomas, distinct from classical large zona fasciculata-like adenomas. The
inverse correlation between APA size and aldosterone synthase expression prompted
us to undertake a systematic study of genotype-phenotype relationships. After a
microarray comparing tumor subtypes, in which NPNT (nephronectin) was the most
highly (>12-fold) upregulated gene in ZG-like APAs, we aimed to determine its
role in physiological and pathological aldosterone production. NPNT was
identified by immunohistochemistry as a secreted matrix protein expressed
exclusively around aldosterone-producing glomeruli in normal adrenal ZG and in
aldosterone-dense ZG-like APAs; the highest expression was in ZG-like APAs with
gain-of-function CTNNB1 mutations, whose removal cured hypertension in our
patients. NPNT was absent from normal zona fasciculata, zona fasciculata-like
APAs, and ZG adjacent to an APA. NPNT production was regulated by canonical Wnt
pathway, and NPNT overexpression or silencing increased or reduced aldosterone,
respectively. NPNT was proadhesive in primary adrenal and APA cells but
antiadhesive and antiapoptotic in immortalized adrenocortical cells. The
discovery of NPNT in the adrenal helped recognition of a common subtype of APAs
and a pathway by which Wnt regulates aldosterone production. We propose that this
arises through NPNT's binding to cell-surface integrins, stimulating cell-cell
contact within glomeruli, which define ZG. Therefore, NPNT or its cognate
integrin could present a novel therapeutic target.
PMID- 28416585
TI - Case of Refractory Hypertension Controlled by Repeated Renal Denervation and
Celiac Plexus Block: A Case of Refractory Sympathetic Overload.
PMID- 28416586
TI - 2-Methoxyestradiol: A 17beta-Estradiol Metabolite With Gender-Independent
Therapeutic Potential.
PMID- 28416584
TI - 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal
Dysfunction in Ovariectomized Female and Intact Male Mice.
AB - Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension
and associated cardiovascular changes in female mice, most likely via production
of 2-methoxyestradiol. This study was conducted to determine whether 2
methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and
end-organ damage in intact Cyp1b1-/-, ovariectomized female, and Cyp1b1+/+ male
mice. Ang II or vehicle was infused for 2 weeks and administered concurrently
with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II
infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II
induced increases in systolic blood pressure, water consumption, urine output,
and proteinuria in intact female Cyp1b1-/- and ovariectomized mice. 2
Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water
intake, urine output, and proteinuria in Cyp1b1+/+ male mice. Treatment with 2
methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1-/-
and ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice and Cyp1b1+/+ male mice. 2
Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of
angiotensinogen in intact Cyp1b1-/- and ovariectomized Cyp1b1+/+ and Cyp1b1-/-
female mice but not in Cyp1b1+/+ male mice. The G protein-coupled estrogen
receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood
pressure and renal function in Cyp1b1+/+ female mice. These data suggest that 2
methoxyestradiol reduces Ang II-induced hypertension and associated end-organ
damage in intact Cyp1b1-/-, ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice,
and Cyp1b1+/+ male mice independent of G protein-coupled estrogen receptor 1.
Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating
hypertension and associated pathogenesis in postmenopausal females, and in males.
PMID- 28416587
TI - Cardiovascular outcomes with an inhaled beta2-agonist/corticosteroid in patients
with COPD at high cardiovascular risk.
AB - OBJECTIVES: Cardiovascular disease (CVD) and chronic obstructive pulmonary
disease (COPD) often coexist. We assessed the effect of inhaled COPD treatments
on CVD outcomes and safety in patients with COPD and at heightened CVD risk.
METHODS: The SUMMIT (Study to Understand Mortality and MorbidITy) was a
multicentre, randomised, double-blind, placebo-controlled, event-driven trial in
16 485 patients with moderate COPD who had or were at high risk of CVD. Here, we
assessed the prespecified secondary endpoint of time to first on-treatment
composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or
transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD
adverse events across the four groups: once-daily inhaled placebo (n=4111), long
acting beta2-agonist (vilanterol (VI) 25 ug; n=4118), corticosteroid (fluticasone
furoate (FF) 100 ug; n=4135) and combination therapy (FF/VI; n=4121). RESULTS:
Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with
overt CVD (66%). The composite CVD endpoint occurred in 688 patients (first
event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%),
and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI
0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93,
95% CI 0.75 to 1.14). Outcomes were similar among all subgroups. Adverse events,
including palpitations and arrhythmias, did not differ by treatment. CONCLUSIONS:
In patients with COPD with moderate airflow limitation and heightened CVD risk,
treatment with inhaled VI, FF or their combination has an excellent safety
profile and does not impact CVD outcomes. TRIAL REGISTRATION NUMBER: NCT01313676.
PMID- 28416588
TI - Association between mutation status and left ventricular reverse remodelling in
dilated cardiomyopathy.
AB - OBJECTIVE: To explore the genetic landscape of a well selected dilated
cardiomyopathy (DCM) cohort, assessing the possible relation between different
genotypes and left ventricular reverse remodelling (LVRR). METHODS: A cohort of
152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been
studied by next-generation sequencing (NGS). Patients were grouped into different
'gene-clusters' with functionally homogeneous genetic backgrounds. LVRR was
defined by left ventricular ejection fraction normalisation or increase >=10%
associated with normalisation in indexed left ventricular end-diastolic diameter
or relative decrease >=10% at 24 months follow-up. RESULTS: A pathogenic disease
related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%)
LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18
(12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features
were similar throughout the different genotypes. A significant relationship was
found between gene cluster subgroups and LVRR, with a lower rate of LVRR in
structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p<0.05
vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare
variants were independently and inversely associated with LVRR when adjusted for
clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011).
CONCLUSIONS: NGS confirmed a high genetic diagnostic yield in DCM. A specific
'gene-clusters' classification based on functional similarities in different
genes might be helpful in the clinical management of genetically determined DCM.
In this study, structural cytoskeleton Z-disk gene rare variants were
independently associated with a lower rate of LVRR at follow-up.
PMID- 28416589
TI - Multimodality imaging of the tricuspid valve with implication for percutaneous
repair approaches.
AB - Nowadays some percutaneous options for tricuspid valve (TV) repair are available:
Tricinch (4Tech Cardio, Galway, Ireland) mimicking the Kay procedure, Trialign
(Mitralign, Boston, MA, USA) aiming to bicuspidise TV, MitraClip (Abbott
Vascular, Abbott Park, Illinois, USA) mimicking Alfieri's stitch, direct
transcatheter annuloplasty with Cardioband (Valtech Cardio, Or Yehuda, Israel)
and transcatheter Forma Repair (Edwards Lifesciences, Irvine, California, USA)
providing a surface for leaflet coaptation. A multimodality imaging approach is
fundamental for defining the pathophysiology of tricuspid regurgitation (TR),
preprocedural planning and intraprocedural monitoring. Both 2-dimensional and 3
dimensional (3D) transthoracic echocardiography and transoesophageal
echocardiography (TOE) are essential for grading and anatomical characterisation
of TR, and evaluation of dimensions and function of right ventricle (RV) and
estimation of pulmonary pressure. In particular, 3D echocardiography provides a
better anatomical definition of TV apparatus and tricuspid annulus (TA) and
additional information about the anatomical relationships of TV and surrounding
structures. CT offers complementary information during the preprocedural planning
especially for procedures targeting TA such as annular structure and dimensions,
quality and amount of annular tissue and its relationship with the right coronary
artery, and the sizing of the inferior vena cava. Moreover, appropriate patient
selection is crucial. The best candidate seems to be a patient with functional TR
due to predominant annular dilatation with modest apical tethering, at least
partial preservation of leaflets coaptation, not severe pulmonary hypertension
and not advanced RV dilation and dysfunction. An example of intraprocedural
multimodality imaging approach with TOE, fluoroscopy, angiography and
intracardiac echocardiography is also reported.
PMID- 28416591
TI - Investigations for tuberculosis contacts: what are the real issues of all the
efforts?
PMID- 28416593
TI - Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and
Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small
GTPase.
AB - Multiple components have been identified that exhibit different stabilities for
aversive olfactory memory in Drosophila These components have been defined by
behavioral and genetic studies and genes specifically required for a specific
component have also been identified. Intermediate-term memory generated after
single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and
anesthesia-resistant memory (ARM), with the latter being more stable. We
determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and
that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas
the full-length form was required for ARM formation. Rgk1 is specifically
accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons
of the mushroom bodies, which play a pivotal role in olfactory memory formation.
A higher than normal Rgk1 level enhanced memory retention, which is consistent
with the result that Rgk1 suppressed Rac-dependent memory decay; these findings
suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that
Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as
a molecular node that resides at KC synapses, where the ASM and ARM pathway may
interact.SIGNIFICANCE STATEMENT Memory consists of multiple components.
Drosophila olfactory memory serves as a fundamental model with which to
investigate the mechanisms that underlie memory formation and has provided
genetic and molecular means to identify the components of memory, namely short
term, intermediate-term, and long-term memory, depending on how long the memory
lasts. Intermediate memory is further divided into anesthesia-sensitive memory
(ASM) and anesthesia-resistant memory (ARM), with the latter being more stable.
We have identified a small GTPase in Drosophila, Rgk1, which plays a pivotal role
in the regulation of olfactory memory stability. Rgk1 is required for both ASM
and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM
formation, whereas the full-length form was required for ARM formation.
PMID- 28416592
TI - 'WNT-er is coming': WNT signalling in chronic lung diseases.
AB - Chronic lung diseases represent a major public health problem with only limited
therapeutic options. An important unmet need is to identify compounds and drugs
that target key molecular pathways involved in the pathogenesis of chronic lung
diseases. Over the last decade, there has been extensive interest in
investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal
alterations have been linked to pulmonary disease pathogenesis and progression.
Here, we comprehensively review the cumulative evidence for WNT pathway
alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis,
pulmonary arterial hypertension, asthma and COPD. While many studies have focused
on the canonical WNT/beta-catenin signalling pathway, recent reports highlight
that non-canonical WNT signalling may also significantly contribute to chronic
lung pathologies; these studies will be particularly featured in this review. We
further discuss recent advances uncovering the role of WNT signalling early in
life, the potential of pharmaceutically modulating WNT signalling pathways and
highlight (pre)clinical studies describing promising new therapies for chronic
lung diseases.
PMID- 28416594
TI - New Repeat Polymorphism in the AKT1 Gene Predicts Striatal Dopamine D2/D3
Receptor Availability and Stimulant-Induced Dopamine Release in the Healthy Human
Brain.
AB - The role of the protein kinase Akt1 in dopamine neurotransmission is well
recognized and has been implicated in schizophrenia and psychosis. However, the
extent to which variants in the AKT1 gene influence dopamine neurotransmission is
not well understood. Here we investigated the effect of a newly characterized
variant number tandem repeat (VNTR) polymorphism in AKT1 [major alleles: L-
(eight repeats) and H- (nine repeats)] on striatal dopamine D2/D3 receptor (DRD2)
availability and on dopamine release in healthy volunteers. We used PET and
[11C]raclopride to assess baseline DRD2 availability in 91 participants. In 54 of
these participants, we also measured intravenous methylphenidate-induced dopamine
release to measure dopamine release. Dopamine release was quantified as the
difference in specific binding of [11C]raclopride (nondisplaceable binding
potential) between baseline values and values following methylphenidate
injection. There was an effect of AKT1 genotype on DRD2 availability at baseline
for the caudate (F(2,90) = 8.2, p = 0.001) and putamen (F(2,90) = 6.6, p =
0.002), but not the ventral striatum (p = 0.3). For the caudate and putamen, LL
showed higher DRD2 availability than HH; HL were in between. There was also a
significant effect of AKT1 genotype on dopamine increases in the ventral striatum
(F(2,53) = 5.3, p = 0.009), with increases being stronger in HH > HL > LL.
However, no dopamine increases were observed in the caudate (p = 0.1) or putamen
(p = 0.8) following methylphenidate injection. Our results provide evidence that
the AKT1 gene modulates both striatal DRD2 availability and dopamine release in
the human brain, which could account for its association with schizophrenia and
psychosis. The clinical relevance of the newly characterized AKT1 VNTR merits
investigation.SIGNIFICANCE STATEMENT The AKT1 gene has been implicated in
schizophrenia and psychosis. This association is likely to reflect modulation of
dopamine signaling by Akt1 kinase since striatal dopamine hyperstimulation is
associated with psychosis and schizophrenia. Here, using PET with
[11C]raclopride, we identified in the AKT1 gene a new variable number tandem
repeat (VNTR) marker associated with baseline striatal dopamine D2/D3 receptor
availability and with methylphenidate-induced striatal dopamine increases in
healthy volunteers. Our results confirm the involvement of the AKT1 gene in
modulating striatal dopamine signaling in the human brain. Future studies are
needed to assess the association of this new VNTR AKT1 variant in schizophrenia
and drug-induced psychoses.
PMID- 28416595
TI - Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson's
Disease.
AB - Oscillations in neural activity play a critical role in neural computation and
communication. There is intriguing new evidence that the nonsinusoidal features
of the oscillatory waveforms may inform underlying physiological and
pathophysiological characteristics. Time-domain waveform analysis approaches
stand in contrast to traditional Fourier-based methods, which alter or destroy
subtle waveform features. Recently, it has been shown that the waveform features
of oscillatory beta (13-30 Hz) events, a prominent motor cortical oscillation,
may reflect near-synchronous excitatory synaptic inputs onto cortical pyramidal
neurons. Here we analyze data from invasive human primary motor cortex (M1)
recordings from patients with Parkinson's disease (PD) implanted with a deep
brain stimulator (DBS) to test the hypothesis that the beta waveform becomes less
sharp with DBS, suggesting that M1 input synchrony may be decreased. We find
that, in PD, M1 beta oscillations have sharp, asymmetric, nonsinusoidal features,
specifically asymmetries in the ratio between the sharpness of the beta peaks
compared with the troughs. This waveform feature is nearly perfectly correlated
with beta-high gamma phase-amplitude coupling (r = 0.94), a neural index
previously shown to track PD-related motor deficit. Our results suggest that the
pathophysiological beta generator is altered by DBS, smoothing out the beta
waveform. This has implications not only for the interpretation of the
physiological mechanism by which DBS reduces PD-related motor symptoms, but more
broadly for our analytic toolkit in general. That is, the often-overlooked time
domain features of oscillatory waveforms may carry critical physiological
information about neural processes and dynamics.SIGNIFICANCE STATEMENT To better
understand the neural basis of cognition and disease, we need to understand how
groups of neurons interact to communicate with one another. For example, there is
evidence that parkinsonian bradykinesia and rigidity may arise from an
oversynchronization of afferents to the motor cortex, and that these symptoms are
treatable using deep brain stimulation. Here we show that the waveform shape of
beta (13-30 Hz) oscillations, which may reflect input synchrony onto the cortex,
is altered by deep brain stimulation. This suggests that mechanistic inferences
regarding physiological and pathophysiological neural communication may be made
from the temporal dynamics of oscillatory waveform shape.
PMID- 28416597
TI - Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape
Encoding.
AB - In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells
contribute to visual object recognition. They receive concurrent inputs from
visual areas V4, V3, and V2. We asked how these different anatomical pathways
shape PIT response properties by deactivating them while monitoring PIT activity
in two male macaques. We found that cooling of V4 or V2|3 did not lead to
consistent changes in population excitatory drive; however, population pattern
analyses showed that V4-based pathways were more important than V2|3-based
pathways. We did not find any image features that predicted decoding accuracy
differences between both interventions. Using the HMAX hierarchical model of
visual recognition, we found that different groups of simulated "PIT" units with
different input histories (lacking "V2|3" or "V4" input) allowed for comparable
levels of object-decoding performance and that removing a large fraction of "PIT"
activity resulted in similar drops in performance as in the cooling experiments.
We conclude that distinct input pathways to PIT relay similar types of shape
information, with V1-dependent V4 cells providing more quantitatively useful
information for overall encoding than cells in V2 projecting directly to
PIT.SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of
the visual system, but most emphasize input transformations across a serial
hierarchy akin to the primary "ventral stream" (V1 -> V2 -> V4 -> IT). However,
the ventral stream also comprises parallel "bypass" pathways: V1 also connects to
V4, and V2 to IT. To explore the advantages of mixing long and short pathways in
the macaque brain, we used cortical cooling to silence inputs to posterior IT and
compared the findings with an HMAX model with parallel pathways.
PMID- 28416598
TI - EBV MicroRNA BART16 Suppresses Type I IFN Signaling.
AB - Type I IFNs play critical roles in orchestrating the antiviral defense by
inducing direct antiviral activities and shaping the adaptive immune response.
Viruses have evolved numerous strategies to specifically interfere with IFN
production or its downstream mediators, thereby allowing successful infection of
the host to occur. The prototypic human gammaherpesvirus EBV, which is associated
with infectious mononucleosis and malignant tumors, harbors many immune-evasion
proteins that manipulate the adaptive and innate immune systems. In addition to
proteins, the virus encodes >40 mature microRNAs for which the functions remain
largely unknown. In this article, we identify EBV-encoded miR-BART16 as a novel
viral immune-evasion factor that interferes with the type I IFN signaling
pathway. miR-BART16 directly targets CREB-binding protein, a key transcriptional
coactivator in IFN signaling, thereby inducing CREB-binding protein
downregulation in EBV-transformed B cells and gastric carcinoma cells. miR-BART16
abrogates the production of IFN-stimulated genes in response to IFN-alpha
stimulation and it inhibits the antiproliferative effect of IFN-alpha on latently
infected BL cells. By obstructing the type I IFN-induced antiviral response, miR
BART16 provides a means to facilitate the establishment of latent EBV infection
and enhance viral replication.
PMID- 28416596
TI - MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading
to fatally debilitating weakness. Because this disease predominantly affects MNs,
we aimed to characterize the distinct expression profile of that cell type to
elucidate underlying disease mechanisms and to identify novel targets that inform
on MN health during ALS disease time course. microRNAs (miRNAs) are short,
noncoding RNAs that can shape the expression profile of a cell and thus often
exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression,
we used Cre recombinase-dependent miRNA tagging and affinity purification in
mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes,
and microglia, we then focused on MN-enriched miRNAs via a comparative analysis
and found that they may functionally distinguish MNs postnatally from other
spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF
harvested from ALS models of MN disease demonstrated that one miRNA (miR-218)
tracked with MN loss and was responsive to an ALS therapy in rodent models.
Therefore, we have used cellular expression profiling tools to define the
distinct miRNA expression of MNs, which is likely to enrich future studies of MN
disease. This approach enabled the development of a novel, drug-responsive marker
of MN disease in ALS rodents.SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis
(ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain
and spinal cord are selectively lost. To develop tools to aid in our
understanding of the distinct expression profiles of MNs and, ultimately, to
monitor MN disease progression, we identified small regulatory microRNAs (miRNAs)
that were highly enriched or exclusive in MNs. The signal for one of these MN
enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where
its levels change as disease progresses, suggesting that it may be a clinically
useful marker of disease status. Furthermore, rats treated with ALS therapy have
restored expression of this MN RNA marker, making it an MN-specific and drug
responsive marker for ALS rodents.
PMID- 28416599
TI - Characterization of T-Dependent and T-Independent B Cell Responses to a Virus
like Particle.
AB - Natural pathogens, such as viruses, often induce T-dependent and T-independent Ab
responses. However, the activation and differentiation of Ag-specific B cells
under these conditions had not been examined in detail. In this study, we used
bacterial phage Qbeta-derived virus-like particles (Qbeta-VLPs) as an immunogen
to examine the T-independent and T-dependent phases of the response in mice.
Using Qbeta-specific cell labeling and enrichment methods developed in this
study, we were able to characterize the rare Ag-specific B cells in detail.
Surprisingly, we found that Qbeta-VLPs could induce Bcl-6 expression in
pregerminal center B cells independently of T cell help. In addition, Qbeta-VLP
induced T-independent responses could lead to isotype-switched and somatically
mutated memory B cells. Finally, in contrast to what has been reported with
several other Ags, long-lived IgG+ memory cells were induced by Qbeta-VLPs, with
IgM+ memory B cells being produced but only evident for a limited time,
suggesting that different types of immunogens may preferentially generate or
maintain IgM+ versus IgG+ memory B cells.
PMID- 28416600
TI - Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine:
Implications for Vaccine Design.
AB - RNA-based vaccines have recently emerged as a promising alternative to the use of
DNA-based and viral vector vaccines, in part because of the potential to simplify
how vaccines are made and facilitate a rapid response to newly emerging
infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM)
replicons encoding an Ag, and formulated with a synthetic delivery system, and
they induce broad-based immune responses in preclinical animal models. In our
study, in vivo imaging shows that after the immunization, SAM Ag expression has
an initial gradual increase. Gene expression profiling in injection-site tissues
from mice immunized with SAM-based vaccine revealed an early and robust induction
of type I IFN and IFN-stimulated responses at the site of injection, concurrent
with the preliminary reduced SAM Ag expression. This SAM vaccine-induced type I
IFN response has the potential to provide an adjuvant effect on vaccine potency,
or, conversely, it might establish a temporary state that limits the initial SAM
encoded Ag expression. To determine the role of the early type I IFN response,
SAM vaccines were evaluated in IFN receptor knockout mice. Our data indicate that
minimizing the early type I IFN responses may be a useful strategy to increase
primary SAM expression and the resulting vaccine potency. RNA sequence
modification, delivery optimization, or concurrent use of appropriate compounds
might be some of the strategies to finalize this aim.
PMID- 28416601
TI - CSReport: A New Computational Tool Designed for Automatic Analysis of Class
Switch Recombination Junctions Sequenced by High-Throughput Sequencing.
AB - B cells ensure humoral immune responses due to the production of Ag-specific
memory B cells and Ab-secreting plasma cells. In secondary lymphoid organs, Ag
driven B cell activation induces terminal maturation and Ig isotype class switch
(class switch recombination [CSR]). CSR creates a virtually unique IgH locus in
every B cell clone by intrachromosomal recombination between two switch (S)
regions upstream of each C region gene. Amount and structural features of CSR
junctions reveal valuable information about the CSR mechanism, and analysis of
CSR junctions is useful in basic and clinical research studies of B cell
functions. To provide an automated tool able to analyze large data sets of CSR
junction sequences produced by high-throughput sequencing (HTS), we designed
CSReport, a software program dedicated to support analysis of CSR recombination
junctions sequenced with a HTS-based protocol (Ion Torrent technology). CSReport
was assessed using simulated data sets of CSR junctions and then used for
analysis of SMU-Salpha and SMU-Sgamma1 junctions from CH12F3 cells and primary
murine B cells, respectively. CSReport identifies junction segment breakpoints on
reference sequences and junction structure (blunt-ended junctions or junctions
with insertions or microhomology). Besides the ability to analyze unprecedentedly
large libraries of junction sequences, CSReport will provide a unified framework
for CSR junction studies. Our results show that CSReport is an accurate tool for
analysis of sequences from our HTS-based protocol for CSR junctions, thereby
facilitating and accelerating their study.
PMID- 28416602
TI - Antigen Receptor Galaxy: A User-Friendly, Web-Based Tool for Analysis and
Visualization of T and B Cell Receptor Repertoire Data.
AB - Antigen Receptor Galaxy (ARGalaxy) is a Web-based tool for analyses and
visualization of TCR and BCR sequencing data of 13 species. ARGalaxy consists of
four parts: the demultiplex tool, the international ImMunoGeneTics information
system (IMGT) concatenate tool, the immune repertoire pipeline, and the somatic
hypermutation (SHM) and class switch recombination (CSR) pipeline. Together they
allow the analysis of all different aspects of the immune repertoire. All
pipelines can be run independently or combined, depending on the available data
and the question of interest. The demultiplex tool allows data trimming and
demultiplexing, whereas with the concatenate tool multiple IMGT/HighV-QUEST
output files can be merged into a single file. The immune repertoire pipeline is
an extended version of our previously published ImmunoGlobulin Galaxy (IGGalaxy)
virtual machine that was developed to visualize V(D)J gene usage. It allows
analysis of both BCR and TCR rearrangements, visualizes CDR3 characteristics
(length and amino acid usage) and junction characteristics, and calculates the
diversity of the immune repertoire. Finally, ARGalaxy includes the newly
developed SHM and CSR pipeline to analyze SHM and/or CSR in BCR rearrangements.
It analyzes the frequency and patterns of SHM, Ag selection (including BASELINe),
clonality (Change-O), and CSR. The functionality of the ARGalaxy tool is
illustrated in several clinical examples of patients with primary
immunodeficiencies. In conclusion, ARGalaxy is a novel tool for the analysis of
the complete immune repertoire, which is applicable to many patient groups with
disturbances in the immune repertoire such as autoimmune diseases, allergy, and
leukemia, but it can also be used to address basic research questions in
repertoire formation and selection.
PMID- 28416603
TI - High-Throughput Immunogenetics for Clinical and Research Applications in
Immunohematology: Potential and Challenges.
AB - Analysis and interpretation of Ig and TCR gene rearrangements in the
conventional, low-throughput way have their limitations in terms of resolution,
coverage, and biases. With the advent of high-throughput, next-generation
sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene
rearrangements is now within reach, which impacts on all main applications of
IG/TR immunogenetic analysis. To bridge the generation gap from low- to high
throughput analysis, the EuroClonality-NGS Consortium has been formed, with the
main objectives to develop, standardize, and validate the entire workflow of
IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease
detection, and 3) repertoire analysis. This concerns the preanalytical (sample
preparation, target choice), analytical (amplification, NGS), and postanalytical
(immunoinformatics) phases. Here we critically discuss pitfalls and challenges of
IG/TR NGS methodology and its applications in hemato-oncology and immunology.
PMID- 28416604
TI - Oncogenic Characterization and Pharmacologic Sensitivity of Activating Fibroblast
Growth Factor Receptor (FGFR) Genetic Alterations to the Selective FGFR Inhibitor
Erdafitinib.
AB - Fibroblast growth factor receptor (FGFR) genetic alterations are frequently
observed in cancer, suggesting that FGFR inhibition may be a promising therapy in
patients harboring these lesions. Identification of predictive and
pharmacodynamic biomarkers to select and monitor patients most likely to respond
to FGFR inhibition will be the key to clinical development of this class of
agents. Sensitivity to FGFR inhibition and correlation with FGFR pathway
activation status were determined in molecularly annotated panels of cancer cell
lines and xenograft models. Pathway inhibition in response to FGFR inhibitor
treatment was assessed in cell lines (both in vitro and in vivo) and in samples
from patients treated with the FGFR inhibitor JNJ-42756493 (erdafitinib).
Frequency of FGFR aberrations was assessed in a panel of NSCLC, breast, prostate,
ovarian, colorectal, and melanoma human tumor tissue samples. FGFR translocations
and gene amplifications present in clinical specimens were shown to display
potent transforming activity associated with constitutive pathway activation.
Tumor cells expressing these FGFR activating mutants displayed sensitivity to the
selective FGFR inhibitor erdafitinib and resulted in suppression of FGFR
phosphorylation and downstream signal transduction. Clinically, patients
receiving erdafitinib showed decreased Erk phosphorylation in tumor biopsies and
elevation of serum phosphate. In a phase I study, a heavily pretreated bladder
cancer patient with an FGFR3-TACC3 translocation experienced a partial response
when treated with erdafitinib. This preclinical study confirmed pharmacodynamics
and identified new predictive biomarkers to FGFR inhibition with erdafitinib and
supports further clinical evaluation of this compound in patients with FGFR
genetic alterations. Mol Cancer Ther; 16(8); 1717-26. (c)2017 AACR.
PMID- 28416605
TI - Photodynamic Therapy Using Photosensitizer-Encapsulated Polymeric Nanoparticle to
Overcome ATP-Binding Cassette Transporter Subfamily G2 Function in Pancreatic
Cancer.
AB - Chlorin-based photosensitizers are commonly used in photodynamic therapy (PDT).
These drugs are effluxed by cell membrane transporters, such as the ATP-binding
cassette subfamily G member 2 (ABCG2). PDT efficacy is limited in tumor cells
expressing high levels of these proteins. Pancreatic cancer cell lines AsPC-1 and
MIA PaCa-2, which have high and low ABCG2 expression, respectively, were used,
and ABCG2-overexpressing MIA PaCa-2 cells were generated. We compared PDT
efficacy between chlorin e6 (Ce6) and cationic photosensitizer-encapsulated
polymeric nanoparticle (PS-pNP), which is comprised with Ce6, polyethylene
glycol, and polyethylenimine. The intracellular concentration of Ce6 was
significantly higher in MIA PaCa-2 cells than in AsPC-1 or ABCG2-overexpressing
MIA PaCa-2 cells. PS-pNP increased intracellular levels of the photosensitizer in
all cell lines. The cell viability experiments indicated increased Ce6 resistance
in ABCG2-overexpressing cells. In contrast, PS-pNP produced similar levels of
cytotoxicity in each of the cancer cell lines tested. Singlet oxygen production
was higher in cells treated with PS-pNP than in those treated with Ce6.
Furthermore, in heterotopic and orthotopic AsPC-1 xenograft mouse models, PDT
using PS-pNP significantly reduced tumor volume in comparison with that of Ce6
treatment. PS-pNP could increase intracellular Ce6 concentration, which was
related with reduced ABCG2-mediated efflux of Ce6, thereby enhancing the effects
of PDT in pancreatic cancer cells. Mol Cancer Ther; 16(8); 1487-96. (c)2017 AACR.
PMID- 28416606
TI - TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative
Breast Cancers via Regulating Alternative Splicing.
AB - Treatment of triple-negative breast cancer (TNBC) has been challenging, and
paclitaxel resistance is one of the major obstacles to the better prognosis.
Deregulation of alternative splicing (AS) may contribute to tumor progression and
chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs
encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival
and therapeutic sensitivity. However, the individual role of TRA2A in cancer
progression has not been reported. Here we report that TRA2A facilitates
proliferation and survival and migration and invasion of TNBC cells. In addition,
TRA2A promotes paclitaxel resistance of TNBC by specifically controlling cancer
related splicing, which is independent of other splicing factors. TRA2A
overexpression could promote AS of CALU, RSRC2, and PALM during paclitaxel
treatment of TNBC cells. The isoform shift of RSRC2 from RSRC2s to RSRC2l leads
to a decreased RSRC2 protein expression, which could contribute to TNBC
paclitaxel resistance. TRA2A can regulate RSRC2 AS by specifically binding
upstream intronic sequence of exon4. Strikingly, TRA2A expression is increased
dramatically in patients with TNBC, and has a close relationship with decreased
RSRC2 expression; both are associated with poor survival of TNBC. Collectively,
our findings suggest that paclitaxel targets the TRA2A-RSRC2 splicing pathway,
and deregulated TRA2A and RSRC2 expression may confer paclitaxel resistance. In
addition to providing a novel molecular mechanism of cancer-related splicing
dysregulation, our study demonstrates that expression of TRA2A in conjunction
with RSRC2 may provide valuable molecular biomarker evidence for TNBC clinical
treatment decisions and patient outcome. Mol Cancer Ther; 16(7); 1377-88. (c)2017
AACR.
PMID- 28416607
TI - Human milk oligosaccharides inhibit growth of group B Streptococcus.
AB - Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of
invasive bacterial infections in newborns, typically acquired vertically during
childbirth secondary to maternal vaginal colonization. Human milk
oligosaccharides (HMOs) have important nutritional and biological activities that
guide the development of the immune system of the infant and shape the
composition of normal gut microbiota. In this manner, HMOs help protect against
pathogen colonization and reduce the risk of infection. In the course of our
studies of HMO-microbial interactions, we unexpectedly uncovered a novel HMO
property to directly inhibit the growth of GBS independent of host immunity. By
separating different HMO fractions through multidimensional chromatography, we
found the bacteriostatic activity to be confined to specific non-sialylated HMOs
and synergistic with a number of conventional antibiotic agents. Phenotypic
screening of a GBS transposon insertion library identified a mutation within a
GBS-specific gene encoding a putative glycosyltransferase that confers resistance
to HMOs, suggesting that HMOs may function as an alternative substrate to modify
a GBS component in a manner that impairs growth kinetics. Our study uncovers a
unique antibacterial role for HMOs against a leading neonatal pathogen and
expands the potential therapeutic utility of these versatile molecules.
PMID- 28416608
TI - Hyper-O-GlcNAcylation activates nuclear factor kappa-light-chain-enhancer of
activated B cells (NF-kappaB) signaling through interplay with phosphorylation
and acetylation.
AB - O-GlcNAcylation is the covalent addition of an O-linked beta-N-acetylglucosamine
(O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of
cytosolic and nuclear proteins. O-GlcNAcylation, analogous to phosphorylation,
plays critical roles in gene expression through direct modification of
transcription factors, such as NF-kappaB. Aberrantly increased NF-kappaB O
GlcNAcylation has been linked to NF-kappaB constitutive activation and cancer
development. Therefore, it is of a great biological and clinical significance to
dissect the molecular mechanisms that tune NF-kappaB activity. Recently, we and
others have shown that O-GlcNAcylation affects the phosphorylation and
acetylation of NF-kappaB subunit p65/RelA. However, the mechanism of how O
GlcNAcylation activates NF-kappaB signaling through phosphorylation and
acetylation is not fully understood. In this study, we mapped O-GlcNAcylation
sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. O-GlcNAcylation
of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent
activating acetylation of p65 at Lys-310, contributing to NF-kappaB
transcriptional activation. Moreover, elevation of O-GlcNAcylation by
overexpression of OGT increased the expression of p300, IKKalpha, and IKKbeta and
promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing
to NF-kappaB activation. In addition, we also identified phosphorylation of p65
at Thr-308, which might impair the O-GlcNAcylation of p65 at Thr-305. These
results indicate mechanisms through which both non-pathological and oncogenic O
GlcNAcylation regulate NF-kappaB signaling through interplay with phosphorylation
and acetylation.
PMID- 28416609
TI - CD36 receptor regulates malaria-induced immune responses primarily at early blood
stage infection contributing to parasitemia control and resistance to mortality.
AB - In malaria, CD36 plays several roles, including mediating parasite sequestration
to host organs, phagocytic clearance of parasites, and regulation of immunity.
Although the functions of CD36 in parasite sequestration and phagocytosis have
been clearly defined, less is known about its role in malaria immunity. Here, to
understand the function of CD36 in malaria immunity, we studied parasite growth,
innate and adaptive immune responses, and host survival in WT and Cd36-/- mice
infected with a non-lethal strain of Plasmodium yoelii Compared with Cd36-/-
mice, WT mice had lower parasitemias and were resistant to death. At early but
not at later stages of infection, WT mice had higher circulatory proinflammatory
cytokines and lower anti-inflammatory cytokines than Cd36-/- mice. WT mice showed
higher frequencies of proinflammatory cytokine-producing and lower frequencies of
anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer
cells than Cd36-/- mice. Cytokines produced by co-cultures of DCs from infected
mice and ovalbumin-specific, MHC class II-restricted alpha/beta (OT-II) T cells
reflected CD36-dependent DC function. WT mice also showed increased Th1 and
reduced Th2 responses compared with Cd36-/- mice, mainly at early stages of
infection. Furthermore, in infected WT mice, macrophages and neutrophils
expressed higher levels of phagocytic receptors and showed enhanced phagocytosis
of parasite-infected erythrocytes than those in Cd36-/- mice in an IFN-gamma
dependent manner. However, there were no differences in malaria-induced humoral
responses between WT and Cd36-/- mice. Overall, the results show that CD36 plays
a significant role in controlling parasite burden by contributing to
proinflammatory cytokine responses by DCs and natural killer cells, Th1
development, phagocytic receptor expression, and phagocytic activity.
PMID- 28416610
TI - Evidence for shear-mediated Ca2+ entry through mechanosensitive cation channels
in human platelets and a megakaryocytic cell line.
AB - The role of mechanosensitive (MS) Ca2+-permeable ion channels in platelets is
unclear, despite the importance of shear stress in platelet function and life
threatening thrombus formation. We therefore sought to investigate the expression
and functional relevance of MS channels in human platelets. The effect of shear
stress on Ca2+ entry in human platelets and Meg-01 megakaryocytic cells loaded
with Fluo-3 was examined by confocal microscopy. Cells were attached to glass
coverslips within flow chambers that allowed applications of physiological and
pathological shear stress. Arterial shear (1002.6 s-1) induced a sustained
increase in [Ca2+] i in Meg-01 cells and enhanced the frequency of repetitive
Ca2+ transients by 80% in platelets. These Ca2+ increases were abrogated by the
MS channel inhibitor Grammostola spatulata mechanotoxin 4 (GsMTx-4) or by
chelation of extracellular Ca2+ Thrombus formation was studied on collagen-coated
surfaces using DiOC6-stained platelets. In addition, [Ca2+] i and functional
responses of washed platelet suspensions were studied with Fura-2 and light
transmission aggregometry, respectively. Thrombus size was reduced 50% by GsMTx
4, independently of P2X1 receptors. In contrast, GsMTx-4 had no effect on
collagen-induced aggregation or on Ca2+ influx via TRPC6 or Orai1 channels and
caused only a minor inhibition of P2X1-dependent Ca2+ entry. The Piezo1 agonist,
Yoda1, potentiated shear-dependent platelet Ca2+ transients by 170%. Piezo1 mRNA
transcripts and protein were detected with quantitative RT-PCR and Western
blotting, respectively, in both platelets and Meg-01 cells. We conclude that
platelets and Meg-01 cells express the MS cation channel Piezo1, which may
contribute to Ca2+ entry and thrombus formation under arterial shear.
PMID- 28416611
TI - The deubiquitinating enzyme Usp14 allosterically inhibits multiple proteasomal
activities and ubiquitin-independent proteolysis.
AB - The proteasome-associated deubiquitinating enzyme Usp14/Ubp6 inhibits protein
degradation by catalyzing substrate deubiquitination and by poorly understood
allosteric actions. However, upon binding a ubiquitin chain, Usp14 enhances
proteasomal degradation by stimulating ATP and peptide degradation. These studies
were undertaken to clarify these seemingly opposite regulatory roles of Usp14 and
their importance. To learn how the presence of Usp14 on 26S proteasomes
influences its different activities, we compared enzymatic and regulatory
properties of 26S proteasomes purified from wild-type mouse embryonic fibroblast
cells and those lacking Usp14. The proteasomes lacking Usp14 had higher basal
peptidase activity than WT 26S, and this activity was stimulated to a greater
extent by adenosine 5'-O-(thiotriphosphate) (ATPgammaS) than with WT particles.
These differences were clear even though Usp14 is present on only a minor
fraction (30-40%) of the 26S in WT mouse embryonic fibroblast cells. Addition of
purified Usp14 to the WT and Usp14-defficient proteasomes reduced both their
basal peptidase activity and the stimulation by ATPgammaS. Usp14 inhibits these
processes allosterically because a catalytically inactive Usp14 mutant also
inhibited them. Proteasomes lacking Usp14 also exhibited greater deubiquitinating
activity by Rpn11 and greater basal ATPase activity than WT particles. ATP
hydrolysis by WT proteasomes is activated if they bind a ubiquitinated protein,
which is loosely folded. Surprisingly, proteasomes lacking Usp14 could be
activated by such proteins even without a ubiquitin chain present. Furthermore,
proteasomes lacking Usp14 are much more active in degrading non-ubiquitinated
proteins (e.g. Sic1) than WT particles. Thus, without a ubiquitinated substrate
present, Usp14 suppresses multiple proteasomal activities, especially basal ATP
consumption and degradation of non-ubiquitinated proteins. These allosteric
effects thus reduce ATP hydrolysis by inactive proteasomes and nonspecific
proteolysis and enhance proteasomal specificity for ubiquitinated proteins.
PMID- 28416612
TI - A biochemical and biophysical model of G-quadruplex DNA recognition by positive
coactivator of transcription 4.
AB - DNA sequences that are guanine-rich have received considerable attention because
of their potential to fold into a secondary, four-stranded DNA structure termed G
quadruplex (G4), which has been implicated in genomic instability and some human
diseases. We have previously identified positive coactivator of transcription
(PC4), a single-stranded DNA (ssDNA)-binding protein, as a novel G4 interactor.
Here, to expand on these previous observations, we biochemically and
biophysically characterized the interaction between PC4 and G4DNA. PC4 can bind
alternative G4DNA topologies with a low nanomolar Kd value of ~2 nm, similar to
that observed for ssDNA. In consideration of the different structural features
between G4DNA and ssDNA, these binding data indicated that PC4 can interact with
G4DNA in a manner distinct from ssDNA. The stoichiometry of the PC4-G4 complex
was 1:1 for PC4 dimer:G4 substrate. PC4 did not enhance the rate of folding of
G4DNA, and formation of the PC4-G4DNA complex did not result in unfolding of the
G4DNA structure. We assembled a G4DNA structure flanked by duplex DNA. We find
that PC4 can interact with this G4DNA, as well as the complementary C-rich
strand. Molecular docking simulations and DNA footprinting experiments suggest a
model where a PC4 dimer accommodates the DNA with one monomer on the G4 strand
and the second monomer bound to the C-rich strand. Collectively, these data
provide a novel mode of PC4 binding to a DNA secondary structure that remains
within the framework of the model for binding to ssDNA. Additionally,
consideration of the PC4-G4DNA interaction could provide insight into the
biological functions of PC4, which remain incompletely understood.
PMID- 28416615
TI - Spotlight on the April 18 issue.
PMID- 28416613
TI - Hypoxia-inducible factor 1alpha activates insulin-induced gene 2 (Insig-2)
transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase
in the liver.
AB - Cholesterol synthesis is a highly oxygen-consuming process. As such, oxygen
deprivation (hypoxia) limits cholesterol synthesis through incompletely
understood mechanisms mediated by the oxygen-sensitive transcription factor
hypoxia-inducible factor 1alpha (HIF-1alpha). We show here that HIF-1alpha links
pathways for oxygen sensing and feedback control of cholesterol synthesis in
human fibroblasts by directly activating transcription of the INSIG-2 gene. Insig
2 is one of two endoplasmic reticulum membrane proteins that inhibit cholesterol
synthesis by mediating sterol-induced ubiquitination and subsequent endoplasmic
reticulum-associated degradation of the rate-limiting enzyme in the pathway, HMG
CoA reductase (HMGCR). Consistent with the results in cultured cells, hepatic
levels of Insig-2 mRNA were enhanced in mouse models of hypoxia. Moreover,
pharmacologic stabilization of HIF-1alpha in the liver stimulated HMGCR
degradation via a reaction that requires the protein's prior ubiquitination and
the presence of the Insig-2 protein. In summary, our results show that HIF-1alpha
activates INSIG-2 transcription, leading to accumulation of Insig-2 protein,
which binds to HMGCR and triggers its accelerated ubiquitination and degradation.
These results indicate that HIF-mediated induction of Insig-2 and degradation of
HMGCR are physiologically relevant events that guard against wasteful oxygen
consumption and inappropriate cell growth during hypoxia.
PMID- 28416616
TI - Editors' Note.
PMID- 28416617
TI - Letter re: Cognitive reserve in frontotemporal degeneration: Neuroanatomic and
neuropsychological evidence.
PMID- 28416614
TI - Modeling Combined Immunosuppressive and Anti-inflammatory Effects of
Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of
Naproxen.
AB - Dexamethasone (DEX), a widely prescribed corticosteroid, has long been the
cornerstone of the treatment of inflammation and immunologic dysfunctions in
rheumatoid arthritis. Corticosteroids are frequently used in combination with
other antirheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs)
and disease-modifying antirheumatic drugs to mitigate disease symptoms and
minimize unwanted effects. We explored the steroid dose-sparing potential of the
NSAID naproxen (NPX) with in vitro and in vivo studies. The single and joint
suppressive effects of DEX and NPX on the in vitro mitogen-induced proliferation
of T lymphocytes in blood and their anti-inflammatory actions on paw edema were
investigated in female and male Lewis rats with collagen-induced arthritis (CIA).
As expected, DEX was far more potent than NPX in these systems. Mathematical
models incorporating an interaction term psi were applied to quantitatively
assess the nature and intensity of pharmacodynamic interactions between DEX and
NPX. Modest synergistic effects of the two drugs were found in suppressing the
mitogenic response of T lymphocytes. A pharmacokinetic/pharmacodynamic/disease
progression model integrating dual drug inhibition quantitatively described the
pharmacokinetics, time-course of single and joint anti-inflammatory effects (paw
edema), and sex differences in CIA rats, and indicated additive effects of DEX
and NPX. Further model simulations demonstrated the promising steroid-sparing
potential of NPX in CIA rats, with the beneficial effects of the combination
therapy more likely in males than females.
PMID- 28416618
TI - Author response: Cognitive reserve in frontotemporal degeneration: Neuroanatomic
and neuropsychological evidence.
PMID- 28416619
TI - Letter re: Tuberculous optochiasmatic arachnoiditis and vision loss.
PMID- 28416621
TI - Tuberculous optochiasmatic arachnoiditis and vision loss.
PMID- 28416620
TI - Author response: Tuberculous optochiasmatic arachnoiditis and vision loss.
PMID- 28416622
TI - Clinical Reasoning: A child with delayed motor milestones and ptosis.
PMID- 28416623
TI - Teaching NeuroImages: Acute Parinaud syndrome.
PMID- 28416624
TI - Teaching Video NeuroImages: Maneuvers to elicit opsoclonus in opsoclonus
myoclonus syndrome.
PMID- 28416625
TI - Letter by Sposato et al Regarding Article, "Stroke as the Initial Manifestation
of Atrial Fibrillation: The Framingham Heart Study".
PMID- 28416627
TI - Response by Lubitz et al to Letter Regarding Article, "Stroke as the Initial
Manifestation of Atrial Fibrillation: The Framingham Heart Study".
PMID- 28416626
TI - Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND AND PURPOSE: The safety and efficacy of restarting anticoagulation
therapy after intracranial hemorrhage (ICH) remain unclear. We performed a
systematic review and meta-analysis to summarize the associations of
anticoagulation resumption with the subsequent risk of ICH recurrence and
thromboembolism. METHODS: We searched published medical literature to identify
cohort studies involving adults with anticoagulation-associated ICH. Our
predictor variable was resumption of anticoagulation. Outcome measures were
thromboembolic events (stroke and myocardial infarction) and recurrence of ICH.
After assessing study heterogeneity and publication bias, we performed a meta
analysis using random-effects models to assess the strength of association
between anticoagulation resumption and our outcomes. RESULTS: Eight studies were
eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all
studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of
anticoagulation was associated with a significantly lower risk of thromboembolic
complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45;
Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of
recurrent ICH after reinstatement of anticoagulation therapy, although there was
significant heterogeneity among included studies (pooled relative risk, 1.01; 95%
confidence interval, 0.58-1.77; Q=24.68, P for heterogeneity <0.001). No
significant publication bias was detected in our analyses. CONCLUSIONS: In
observational studies, reinstitution of anticoagulation after ICH was associated
with a lower risk of thromboembolic complications and a similar risk of ICH
recurrence. Randomized clinical trials are needed to determine the true risk
benefit profile of anticoagulation resumption after ICH.
PMID- 28416628
TI - Impaired Glutamatergic Neurotransmission in the Ventromedial Hypothalamus May
Contribute to Defective Counterregulation in Recurrently Hypoglycemic Rats.
AB - The objectives of this study were to understand the role of glutamatergic
neurotransmission in the ventromedial hypothalamus (VMH) in response to
hypoglycemia and to elucidate the effects of recurrent hypoglycemia (RH) on this
neurotransmitter. We 1) measured changes in interstitial VMH glutamate levels by
using microdialysis and biosensors, 2) identified the receptors that mediate
glutamate's stimulatory effects on the counterregulatory responses, 3) quantified
glutamate metabolic enzyme levels in the VMH, 4) examined astrocytic glutamate
reuptake mechanisms, and 5) used 1H-[13C]-nuclear magnetic resonance (NMR)
spectroscopy to evaluate the effects of RH on neuronal glutamate metabolism. We
demonstrated that glutamate acts through kainic acid receptors in the VMH to
augment counterregulatory responses. Biosensors showed that the normal transient
rise in glutamate levels in response to hypoglycemia is absent in RH animals.
More importantly, RH reduced extracellular glutamate concentrations partly as a
result of decreased glutaminase expression. Decreased glutamate was also
associated with reduced astrocytic glutamate transport in the VMH. NMR analysis
revealed a decrease in [4-13C]glutamate but unaltered [4-13C]glutamine
concentrations in the VMH of RH animals. The data suggest that glutamate release
is important for proper activation of the counterregulatory response to
hypoglycemia and that impairment of glutamate metabolic and resynthetic pathways
with RH may contribute to counterregulatory failure.
PMID- 28416629
TI - Individual differences in fear extinction and anxiety-like behavior.
AB - There is growing appreciation for the substantial individual differences in the
acquisition and inhibition of aversive associations, and the insights this might
give into identifying individuals particularly vulnerable to stress and
psychopathology. We examined whether animals that differed in rate of extinction
(i.e., Fast versus Slow) were different in their response to an acute stress in
adulthood or following a chronic stress that occurred either early or later in
life. We found that Slow Extinguishers had significantly poorer extinction
retention than Fast Extinguishers, but an acute stressor did not differentially
affect anxiety-like behavior in the two groups. Further, while exposure to
chronic stress in adulthood did not impact on the extinction phenotypes or
anxiety-like behavior, exposure to chronic stress early in life affected both
extinction retention and anxiety-like behavior. These findings have implications
for the development of a more nuanced approach to identifying those most at risk
of anxiety disorders.
PMID- 28416630
TI - Common microbehavioral "footprint" of two distinct classes of conditioned
aversion.
AB - Avoiding unfavorable situations is a vital skill and a constant task for any
animal. Situations can be unfavorable because they feature something that the
animal wants to escape from, or because they do not feature something that it
seeks to obtain. We investigate whether the microbehavioral mechanisms by which
these two classes of aversion come about are shared or distinct. We find that
larval Drosophila avoid odors either previously associated with a punishment, or
previously associated with the lack of a reward. These two classes of conditioned
aversion are found to be strikingly alike at the microbehavioral level. In both
cases larvae show more head casts when oriented toward the odor source than when
oriented away, and direct fewer of their head casts toward the odor than away
when oriented obliquely to it. Thus, conditioned aversion serving two
qualitatively different functions-escape from a punishment or search for a reward
is implemented by the modulation of the same microbehavioral features. These
features also underlie conditioned approach, albeit with opposite sign. That is,
the larvae show conditioned approach toward odors previously associated with a
reward, or with the lack of a punishment. In order to accomplish both these
classes of conditioned approach the larvae show fewer head casts when oriented
toward an odor, and direct more of their head casts toward it when they are
headed obliquely. Given that the Drosophila larva is a genetically tractable
model organism that is well suited to study simple circuits at the single-cell
level, these analyses can guide future research into the neuronal circuits
underlying conditioned approach and aversion, and the computational principles of
conditioned search and escape.
PMID- 28416631
TI - Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of
plasticity and memory by manipulating actin remodeling.
AB - Recent human exome-sequencing studies have implicated polymorphic Brg1-associated
factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in
several intellectual disabilities and cognitive disorders, including autism.
However, it remains unclear how mutations in BAF complexes result in impaired
cognitive function. Post-mitotic neurons express a neuron-specific assembly,
nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b
is essential for the differentiation of neuronal precursor cells into neurons. We
generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bDeltaSB2). Long
term synaptic potentiation (LTP) and long-term memory, both of which are
associated with phosphorylation of the actin severing protein cofilin, were
assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically
delivered into the hippocampus of BAF53bDeltaSB2 mice in an effort to rescue LTP
and memory. BAF53bDeltaSB2 mutant mice show impairments in phosphorylation of
synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory
deficits are rescued by overexpression of a phosphorylation mimetic of cofilin.
Baseline physiology and behavior were not affected by the mutation or the
experimental treatment. This study suggests a potential link between nBAF
function, actin cytoskeletal remodeling at the dendritic spine, and memory
formation. This work shows that a targeted manipulation of synaptic function can
rescue adult plasticity and memory deficits caused by manipulations of nBAF, and
thereby provides potential novel avenues for therapeutic development for multiple
intellectual disability disorders.
PMID- 28416632
TI - Null EPAC mutants reveal a sequential order of versatile cAMP effects during
Drosophila aversive odor learning.
AB - Here, we define a role of the cAMP intermediate EPAC in Drosophila aversive odor
learning by means of null epac mutants. Complementation analysis revealed that
EPAC acts downstream from the rutabaga adenylyl cyclase and in parallel to
protein kinase A. By means of targeted knockdown and genetic rescue we identified
mushroom body Kenyon cells (KCs) as a necessary and sufficient site of EPAC
action. We provide mechanistic insights by analyzing acquisition dynamics and
using the "performance increment" as a means to access the trial-based sequential
organization of odor learning. Thereby we show that versatile cAMP-dependent
mechanisms are engaged within a sequential order that correlate to individual
trials of the training session.
PMID- 28416633
TI - Intrusions in episodic memory: reconsolidation or interference?
AB - It would be profoundly important if reconsolidation research in animals and other
memory domains generalized to human episodic memory. A 3-d-list-discrimination
procedure, based on free recall of objects, with a contextual reminder cue (the
testing room), has been thought to demonstrate reconsolidation of human episodic
memory (as noted in a previous study). Our goal was to replicate the central
result, a high intrusion rate during recall of the target list, and evaluate the
reconsolidation account relative to an alternative account, based on state
dependent learning and interference. First, replication was not straightforward
(Experiment 1). Second, using a very unique, highly salient context (Experiment
2), the method produced a qualitative replication, but it was small in magnitude.
A critical assumption of the reconsolidation account, that the target list is
reactivated and destabilized during re-exposure to the study context, was not
supported (Experiment 3). Although troubling for the reconsolidation account, the
findings can be easily accommodated by an alternative account that does not
assume additional neurobiological processes underlying the destabilization of
consolidated memories, instead explaining intrusion rates simply in terms of well
established cognitive effects, such as item-to-context binding and interference
during retrieval.
PMID- 28416634
TI - A Molecular Mechanism To Switch the Aryl Hydrocarbon Receptor from a
Transcription Factor to an E3 Ubiquitin Ligase.
AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
that is known as a mediator of toxic responses. Recently, it was shown that the
AhR has dual functions. Besides being a transcription factor, it also possesses
an intrinsic E3 ubiquitin ligase function that targets, e.g., the steroid
receptors for proteasomal degradation. The aim of this study was to identify the
molecular switch that determines whether the AhR acts as a transcription factor
or an E3 ubiquitin ligase. To do this, we used the breast cancer cell line MCF7,
which expresses a functional estrogen receptor alpha (ERalpha) signaling pathway.
Our data suggest that aryl hydrocarbon receptor nuclear translocator (ARNT) plays
an important role in the modulation of the dual functions of the AhR. ARNT
knockdown dramatically impaired the transcriptional activation properties of the
ligand-activated AhR but did not affect its E3 ubiquitin ligase function. The
availability of ARNT itself is modulated by another basic helix-loop-helix (bHLH)
Per-ARNT-SIM (PAS) protein, the repressor of AhR function (AhRR). MCF7 cells
overexpressing the AhRR showed lower ERalpha protein levels, reduced
responsiveness to estradiol, and reduced growth rates. Importantly, when these
cells were used to produce estrogen-dependent xenograft tumors in SCID mice, we
also observed lower ERalpha protein levels and a reduced tumor mass, implying a
tumor-suppressive-like function of the AhR in MCF7 xenograft tumors.
PMID- 28416635
TI - VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell
Cycle Transcription Factor FoxM1.
AB - The oncogenic transcription factor FoxM1 plays a vital role in cell cycle
progression, is activated in numerous human malignancies, and is linked to
chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase
and its substrate receptor, VprBP/DCAF1 (CRL4VprBP), which we show regulate FoxM1
ubiquitylation and degradation. Paradoxically, we also found that the substrate
receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of
FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression
strongly activates a FoxM1 transcriptional reporter. VprBP binding to CRL4 is
reduced during mitosis, and our data suggest that VprBP activation of FoxM1 is
ligase independent. This implies a nonproteolytic activation mechanism that is
reminiscent of, yet distinct from, the ubiquitin-dependent transactivation of the
oncoprotein Myc by other E3s. Significantly, VprBP protein levels were
upregulated in high-grade serous ovarian patient tumors, where the FoxM1
signature is amplified. These data suggest that FoxM1 abundance and activity are
controlled by VprBP and highlight the functional repurposing of E3 ligase
substrate receptors independent of the ubiquitin system.
PMID- 28416636
TI - p53 Dynamically Directs TFIID Assembly on Target Gene Promoters.
AB - p53 is a central regulator that turns on vast gene networks to maintain cellular
integrity in the presence of various stimuli. p53 activates transcription
initiation in part by aiding recruitment of TFIID to the promoter. However, the
precise means by which p53 dynamically interacts with TFIID to facilitate
assembly on target gene promoters remains elusive. To address this key issue, we
have undertaken an integrated approach involving single-molecule fluorescence
microscopy, single-particle cryo-electron microscopy, and biochemistry. Our real
time single-molecule imaging data demonstrate that TFIID alone binds poorly to
native p53 target promoters. p53 unlocks TFIID's ability to bind DNA by
stabilizing TFIID contacts with both the core promoter and a region within p53's
response element. Analysis of single-molecule dissociation kinetics reveals that
TFIID interacts with promoters via transient and prolonged DNA binding modes that
are each regulated by p53. Importantly, our structural work reveals that TFIID's
conversion to a rearranged DNA binding conformation is enhanced in the presence
of DNA and p53. Notably, TFIID's interaction with DNA induces p53 to rapidly
dissociate, which likely leads to additional rounds of p53-mediated recruitment
of other basal factors. Collectively, these findings indicate that p53
dynamically escorts and loads TFIID onto its target promoters.
PMID- 28416638
TI - Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced
Leukemogenesis.
AB - PLZF is a transcription factor that confers aberrant self-renewal in
leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia
(APL) through differentiation block. However, the molecular mechanisms of
aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly
understood. To investigate these mechanisms, comprehensive expression profiling
of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed,
which revealed the involvement of a key transcriptional coactivator, Eya2, a
target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal.
Indeed, PLZF-RARA as well as Plzf rendered those cells immortalized through
upregulation of Eya2. Eya2 also led to immortalization without differentiation
block, while depletion of Eya2 suppressed clonogenicity in cells immortalized by
PLZF-RARA without influence on differentiation and apoptosis. Interestingly,
cancer outlier profile analysis of human samples of acute myeloid leukemia (AML)
in The Cancer Genome Atlas (TCGA) revealed a subtype of AML that strongly
expressed EYA2 In addition, gene set enrichment analysis of human AML samples,
including TCGA data, showed that this subtype of AML was more closely associated
with the properties of leukemic stem cells in its gene expression signature than
other AMLs. Therefore, EYA2 may be a target for molecular therapy in this subtype
of AML, including PLZF-RARA APL.
PMID- 28416639
TI - Absent progesterone receptor expression in the lymph node metastases of ER
positive, HER2-negative breast cancer is associated with relapse on tamoxifen.
AB - AIMS: Progesterone receptor (PR) expression is prognostic in early stage breast
cancer. There are several reports of discordant expression between primary tumour
and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER)
and PR. We sought to determine whether expression of these biomarkers in the
synchronous ALN metastases of ER positive (+), HER2 negative (-) breast cancer
could provide more accurate prognostic information. METHODS: The retrospective
cohort included 229 patients from a single institution with ER+, HER2- breast
cancer who had synchronous ALN metastatic disease (2005-2014). PR expression was
correlated with relapse-free survival, and subset analysis was performed for
patients who received adjuvant tamoxifen or an aromatase inhibitor. RESULTS: One
patient had an ER+ primary tumour, which was ER- in the ALN metastasis. 27
(11.3%) were PR- in the primary tumour and 56 (23.6%) in the ALN metastasis. The
predominant change was from PR+ in the primary tumour to PR- in the lymph node.
Absence of PR expression in the ALN was significantly associated with relapse;
however, this was not the case in the primary tumour. In a subset analysis of
patients taking adjuvant endocrine therapy, poorer prognosis was limited to those
with PR- metastases on tamoxifen (HR=5.203, 95% CI 1.649 to 16.416, p=0.005). No
significant prognostic effect of PR- metastases in patients taking aromatase
inhibitors was seen (HR=1.519, 95% CI 0.675 to 3.418, p=0.312). CONCLUSIONS:
Evaluation of PR expression in ALN metastasis may enable prediction of patients
who are less likely to benefit from adjuvant tamoxifen. This study should be
replicated in other cohorts.
PMID- 28416637
TI - A Kinase-Independent Role for Cyclin-Dependent Kinase 19 in p53 Response.
AB - The human Mediator complex regulates RNA polymerase II transcription genome-wide.
A general factor that regulates Mediator function is the four-subunit kinase
module, which contains either cyclin-dependent kinase 8 (CDK8) or CDK19. Whereas
CDK8 is linked to specific signaling cascades and oncogenesis, the cellular roles
of its paralog, CDK19, are poorly studied. We discovered that osteosarcoma cells
(SJSA) are naturally depleted of CDK8 protein. Whereas stable CDK19 knockdown was
tolerated in SJSA cells, proliferation was reduced. Notably, proliferation
defects were rescued upon the reexpression of wild-type or kinase-dead CDK19.
Comparative RNA sequencing analyses showed reduced expression of mitotic genes
and activation of genes associated with cholesterol metabolism and the p53
pathway in CDK19 knockdown cells. SJSA cells treated with 5-fluorouracil, which
induces metabolic and genotoxic stress and activates p53, further implicated
CDK19 in p53 target gene expression. To better probe the p53 response, SJSA cells
(shCDK19 versus shCTRL) were treated with the p53 activator nutlin-3. Remarkably,
CDK19 was required for SJSA cells to return to a proliferative state after nutlin
3 treatment, and this effect was kinase independent. These results implicate
CDK19 as a regulator of p53 stress responses and suggest a role for CDK19 in
cellular resistance to nutlin-3.
PMID- 28416640
TI - Microsatellite analysis of sporadic and hereditary gynaecological cancer in
routine diagnostics.
AB - Microsatellite instability (MSI) testing is tricky in gynaecological cancers
(GC). Thus, we aimed to describe the instability patterns to improve MSI test
interpretation in sporadic and hereditary GCs. Ninety-five cases, including
uterine and ovarian cancers, with known genetic and immunohistochemical (IHC)
features, were analysed for MSI by a mononucleotide repeats pentaplex (MRP). We
identified 13 ambiguous cases that did not fully meet MSI criteria ('borderline'
cases, B-MSI), which were mainly represented by MSH2/MSH6-deficient and Lynch
syndrome cases. Also, we evaluated nine additional loci of candidate MSI markers
that did not improve the detection of MSI cases, but might be useful for
discordant or borderline samples. In conclusion, although MSI and IHC test are
highly concordant, a subset of ambiguous MSI cases deserves a careful
interpretation in particular when MSH2/MSH6 are involved. RPL22 and SRPR testing
may be useful to integrate MRP panel for the analysis of critical cases.
PMID- 28416641
TI - Unusual presentation of a skin rash.
PMID- 28416642
TI - Estimating the burden of occupational cancer: assessing bias and uncertainty.
AB - BACKGROUND AND OBJECTIVES: We aimed to estimate credibility intervals for the
British occupational cancer burden to account for bias uncertainty, using a
method adapted from Greenland's Monte Carlo sensitivity analysis. METHODS: The
attributable fraction (AF) methodology used for our cancer burden estimates
requires risk estimates and population proportions exposed for each agent/cancer
pair. Sources of bias operating on AF estimator components include non
portability of risk estimates, inadequate models, inaccurate data including
unknown cancer latency and employment turnover and compromises in using the
available estimators. Each source of bias operates on a component of the AF
estimator. Independent prior distributions were estimated for each bias, or
graphical sensitivity analysis was used to identify plausible distribution ranges
for the component variables, with AF recalculated following Monte Carlo repeated
sampling from these distributions. The methods are illustrated using the example
of lung cancer due to occupational exposure to respirable crystalline silica in
men. RESULTS: Results are presented graphically for a hierarchy of biases
contributing to an overall credibility interval for lung cancer and respirable
crystalline silica exposure. An overall credibility interval of 2.0% to 16.2% was
estimated for an AF of 3.9% in men. Choice of relative risk and employment
turnover were shown to contribute most to overall estimate uncertainty. Bias from
using an incorrect estimator makes a much lower contribution. CONCLUSIONS: The
method illustrates the use of credibility intervals to indicate relative
contributions of important sources of uncertainty and identifies important data
gaps; results depend greatly on the priors chosen.
PMID- 28416643
TI - Can serum cytokine profile discriminate irritant-induced and allergen-induced
symptoms? A cross-sectional study in workers mostly exposed to laboratory
animals.
AB - BACKGROUND: In workers exposed mostly to laboratory animals (LA), symptoms may be
due to irritants or allergens. Correct aetiological diagnosis is important for
health surveillance. OBJECTIVES: This study aims to test whether work-related
(WR) allergen-induced symptoms are associated with a cytokine profile distinct
from that due to irritants. METHODS: In a cross-sectional study (n=114), WR
respiratory and/or skin symptoms were assessed through a standardised clinical
examination and sensitisation to rat and/or mouse allergen determined by serum
immunoglobulin E. Serum cytokine concentrations were measured by multiplex
assays. The predefined cytokine profiles 'sensitiser' (interleukin (IL)-4, IL-5,
IL-13, eotaxin-1) and 'irritation' (IL-8, IL-17A, IL-17F, IL-22) were considered
positive, when >=3 concentrations exceeded the 95th percentile of the
asymptomatic non-sensitised group. Results were examined by hierarchical
clustering analyses (HCA) and multiple linear regression. Explorative analyses
were carried out for nine additional cytokines. Exposure to allergens and
endotoxin was assessed in a subpopulation. RESULTS: The prevalence of the profile
'irritation' was comparable in 28 symptomatic non-sensitised workers and 71
asymptomatic non-sensitised workers. HCA showed that nearly all symptomatic non
sensitised workers were gathered in two subclusters, characterised by high IL-17A
levels, but different IL-8 levels. Multiple linear regression identified drug
consumption and current complaints as confounders. Sensitised subjects were too
few (n=14) for testing the profile 'sensitiser'. CONCLUSIONS: In this unselected
population of LA workers, the profile 'irritation' did not prove to be a valuable
health surveillance tool. Low power precluded assessment of the profile
'sensitiser'. The increased IL-17A concentration may originate from irritative
constituents of organic dust.
PMID- 28416644
TI - Evaluation of Different Estimation Methods for Accuracy and Precision in
Biological Assay Validation.
AB - Biological assays (bioassays) are procedures to estimate the potency of a
substance by studying its effects on living organisms, tissues, and cells.
Bioassays are essential tools for gaining insight into biologic systems and
processes including, for example, the development of new drugs and monitoring
environmental pollutants. Two of the most important parameters of bioassay
performance are relative accuracy (bias) and precision. Although general
strategies and formulas are provided in USP<1033>, a comprehensive understanding
of the definitions of bias and precision remain elusive. Additionally, whether
there is a beneficial use of data transformation in estimating intermediate
precision remains unclear. Finally, there are various statistical estimation
methods available that often pose a dilemma for the analyst who must choose the
most appropriate method. To address these issues, we provide both a rigorous
definition of bias and precision as well as three alternative methods for
calculating relative standard deviation (RSD). All methods perform similarly when
the RSD <=10%. However, the USP estimates result in larger bias and root-mean
square error (RMSE) compared to the three proposed methods when the actual
variation was large. Therefore, the USP method should not be used for routine
analysis. For data with moderate skewness and deviation from normality, the
estimates based on the original scale perform well. The original scale method is
preferred, and the method based on log-transformation may be used for noticeably
skewed data.LAY ABSTRACT: Biological assays, or bioassays, are essential in the
development and manufacture of biopharmaceutical products for potency testing and
quality monitoring. Two important parameters of assay performance are relative
accuracy (bias) and precision. The definitions of bias and precision in USP
<1033> are elusive and confusing. Another complicating issue is whether log
transformation should be used for calculating the intermediate precision. It is
often challenging for analysts to pick the most appropriate estimation method. To
address these issues, we give a rigorous definition of bias and precision and
provide three alternative methods of calculating RSD. We demonstrate that the RSD
formula in USP <1033> tends to have larger bias and root-mean-square error (RMSE)
than the three proposed methods.
PMID- 28416645
TI - Performance Stability of Silicone Oxide-Coated Plastic Parenteral Vials.
AB - A new packaging system was developed for parenteral pharmaceuticals that combines
the best attributes of plastic and glass without their respective drawbacks. This
technological advancement is based on the synergy between high-precision
injection-molded plastics and plasma coating technology. The result is a shatter
resistant, optically clear, low-particulate, and chemically durable packaging
system. The demand for this product is driven by the expanding market, regulatory
constraints, and product recalls for injectable drugs and biologics packaged in
traditional glass materials. It is shown that this new packaging system meets or
exceeds the important performance characteristics of glass, especially in
eliminating the glass delamination and breakage that has been observed in many
products. The new packaging system is an engineered, multilayer, glass-coated
plastic composite that provides a chemically stable contact surface and oxygen
barrier performance that exceeds a 2 year shelf life requirement. Evaluation of
the coating system characteristics and performance stability to chemical,
temperature, and mechanical extremes are reported herein.LAY ABSTRACT: A new
packaging system for parenteral pharmaceuticals was developed that combines the
best attributes of plastic and glass without their respective drawbacks. This
technological advancement is based on the synergy between high-precision
injection-molded plastics and plasma coating technology. The result is a shatter
resistant, optically clear, low-particulate, and chemically durable packaging
system. It is shown that this new packaging system meets or exceeds the important
performance characteristics of glass, especially in eliminating the glass
delamination and breakage that has been observed in many products. The new
packaging system is an engineered, multilayer, glass-coated plastic composite
that provides a chemically stable contact surface and oxygen barrier performance
that exceeds a 2 year shelf life requirement. Evaluation of the coating system
characteristics and performance stability to chemical, temperature, and
mechanical extremes are reported herein.
PMID- 28416646
TI - Increasing Patient Safety by Closing the Sterile Production Gap-Part 3-Moist Heat
Resistance of Bioburden.
AB - Terminal sterilization is considered the preferred means for the production of
sterile drug products, as it affords enhanced safety for the patient because the
formulation is sterilized in its sealed, final container. Despite the obvious
patient benefits, the use of terminal sterilization is artificially constrained
by unreasonable expectations for the minimum time-temperature process to be used.
The core misunderstanding with terminal sterilization is the notion that
destruction of a high population of a resistant biological indicator
microorganism is required. More contemporary thinking on sterilization
acknowledges that the bioburden is the actual target in sterilization and its
destruction must be assured. In the application of low-temperature moist heat for
terminal sterilization, especially subsequent to aseptic processing, establishing
the pre-sterilization bioburden to consider has proven challenging. Environmental
monitoring survey data has determined the identity of potential microorganisms
but not their resistance to sterilization. This review article provides
information on the moist heat resistance of vegetative and sporeforming
microorganisms that might be present. The first paper in this series provided the
overall background and described the benefits to patient, producer, and regulator
of low-temperature moist heat for terminal sterilization. The second paper
outlined validation and operational advice that can be used in the
implementation. This final effort concludes the series and provides insight into
potential bioburden and its resistance.LAY ABSTRACT: Terminal sterilization is
considered the preferred means for the production of sterile drug products as it
affords enhanced safety for the patient as the formulation is filled into its
final container, sealed and sterilized. Despite the obvious patient benefits, the
use of terminal sterilization is artificially constrained by unreasonable
expectations for the minimum time-temperature process to be used. The primary
consideration in terminal sterilization is the reliable destruction of the
bioburden. The earlier manuscripts in this series described the principles and
implementation of low temperature terminal sterilization processes where the
sterilization conditions would destroy the expected bioburden present. To
accomplish that reliably knowledge of the bioburden expected resistance to moist
heat is necessary. This review article will identify publications where that data
can be found.
PMID- 28416647
TI - Identifiability, reducibility, and adaptability in allosteric macromolecules.
AB - The ability of macromolecules to transduce stimulus information at one site into
conformational changes at a distant site, termed "allostery," is vital for
cellular signaling. Here, we propose a link between the sensitivity of allosteric
macromolecules to their underlying biophysical parameters, the interrelationships
between these parameters, and macromolecular adaptability. We demonstrate that
the parameters of a canonical model of the mSlo large-conductance Ca2+-activated
K+ (BK) ion channel are non-identifiable with respect to the equilibrium open
probability-voltage relationship, a common functional assay. We construct a
reduced model with emergent parameters that are identifiable and expressed as
combinations of the original mechanistic parameters. These emergent parameters
indicate which coordinated changes in mechanistic parameters can leave assay
output unchanged. We predict that these coordinated changes are used by
allosteric macromolecules to adapt, and we demonstrate how this prediction can be
tested experimentally. We show that these predicted parameter compensations are
used in the first reported allosteric phenomena: the Bohr effect, by which
hemoglobin adapts to varying pH.
PMID- 28416648
TI - Isoflurane modulates activation and inactivation gating of the prokaryotic Na+
channel NaChBac.
AB - Voltage-gated Na+ channels (Nav) have emerged as important presynaptic targets
for volatile anesthetic (VA) effects on synaptic transmission. However, the
detailed biophysical mechanisms by which VAs modulate Nav function remain
unclear. VAs alter macroscopic activation and inactivation of the prokaryotic Na+
channel, NaChBac, which provides a useful structural and functional model of
mammalian Nav Here, we study the effects of the common general anesthetic
isoflurane on NaChBac function by analyzing macroscopic Na+ currents (INa) in
wild-type (WT) channels and mutants with impaired (G229A) or enhanced (G219A)
inactivation. We use a previously described six-state Markov model to analyze
empirical WT and mutant NaChBac channel gating data. The model reproduces the
mean empirical gating manifest in INa time courses and optimally estimates
microscopic rate constants, valences (z), and fractional electrical distances (x)
of forward and backward transitions. The model also reproduces gating observed
for all three channels in the absence or presence of isoflurane, providing
further validation. We show using this model that isoflurane increases forward
activation and inactivation rate constants at 0 mV, which are associated with
estimated chemical free energy changes of approximately -0.2 and -0.7 kcal/mol,
respectively. Activation is voltage dependent (z ~ 2e0, x ~ 0.3), inactivation
shows little voltage dependence, and isoflurane has no significant effect on
either. Forward inactivation rate constants are more than 20-fold greater than
backward rate constants in the absence or presence of isoflurane. These results
indicate that isoflurane modulates NaChBac gating primarily by increasing forward
activation and inactivation rate constants. These findings support accumulating
evidence for multiple sites of anesthetic interaction with the channel.
PMID- 28416649
TI - Optic nerve astrocyte reactivity protects function in experimental glaucoma and
other nerve injuries.
AB - Reactive remodeling of optic nerve head astrocytes is consistently observed in
glaucoma and other optic nerve injuries. However, it is unknown whether this
reactivity is beneficial or harmful for visual function. In this study, we used
the Cre recombinase (Cre)-loxP system under regulation of the mouse glial
fibrillary acidic protein promoter to knock out the transcription factor signal
transducer and activator of transcription 3 (STAT3) from astrocytes and test the
effect this has on reactive remodeling, ganglion cell survival, and visual
function after experimental glaucoma and nerve crush. After injury, STAT3
knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling;
astrocytes largely maintained their honeycomb organization and glial tubes. These
changes were associated with increased loss of ganglion cells and visual function
over a 30-day period. Thus, reactive astrocytes play a protective role,
preserving visual function. STAT3 signaling is an important mediator of various
aspects of the reactive phenotype within optic nerve astrocytes.
PMID- 28416651
TI - AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse
model of tauopathy.
AB - Tauopathies are characterized by the progressive accumulation of
hyperphosphorylated, aggregated forms of tau. Our laboratory has previously
demonstrated that passive immunization with an anti-tau antibody, HJ8.5,
decreased accumulation of pathological tau in a human P301S tau-expressing
transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To
investigate whether the Fc domain of HJ8.5 is required for the therapeutic
effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5
with variable linker lengths, all specific to human tau. Based on different
binding properties, we selected two anti-tau scFvs and tested their efficacy in
vivo by adeno-associated virus-mediated gene transfer to the brain of P301S-tg
mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated
tau in brain tissue of P301S-tg mice, associated with a decrease in detergent
soluble tau species. Interestingly, these mice showed substantial levels of scFvs
in the cerebrospinal fluid without significant effects on total extracellular tau
levels. Therefore, our study provides a novel strategy for anti-tau
immunotherapeutics that potentially limits a detrimental proinflammatory
response.
PMID- 28416650
TI - Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9
elicited IFN response in pDCs.
AB - TLR7/9 signals are capable of mounting massive interferon (IFN) response in
plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the
involvement of epigenetic regulation in this process has not been documented.
Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly
expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN
response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of
the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression
in steady-state pDCs. Mechanistically, CXXC5 is responsible for the recruitment
of DNA demethylase Tet2 to maintain the hypomethylation of a subset of CGIs, a
process coincident with active histone modifications and constitutive
transcription of these CGI-containing genes. Consequently, CXXC5-deficient mice
had compromised early IFN response and became highly vulnerable to infection by
herpes simplex virus and vesicular stomatitis virus. Together, our results
identify CXXC5 as a novel epigenetic regulator for pDC-mediated antiviral
response.
PMID- 28416652
TI - Simplification of the HOSPITAL score for predicting 30-day readmissions.
AB - OBJECTIVE: The HOSPITAL score has been widely validated and accurately identifies
high-risk patients who may mostly benefit from transition care interventions.
Although this score is easy to use, it has the potential to be simplified without
impacting its performance. We aimed to validate a simplified version of the
HOSPITAL score for predicting patients likely to be readmitted. DESIGN AND
SETTING: Retrospective study in 9 large hospitals across 4 countries, from
January through December 2011. PARTICIPANTS: We included all consecutively
discharged medical patients. We excluded patients who died before discharge or
were transferred to another acute care facility. MEASUREMENTS: The primary
outcome was any 30-day potentially avoidable readmission. We simplified the score
as follows: (1) 'discharge from an oncology division' was replaced by 'cancer
diagnosis or discharge from an oncology division'; (2) 'any procedure' was left
out; (3) patients were categorised into two risk groups (unlikely and likely to
be readmitted). The performance of the simplified HOSPITAL score was evaluated
according to its overall accuracy, its discriminatory power and its calibration.
RESULTS: Thirty-day potentially avoidable readmission rate was 9.7% (n=11 307/117
065 patients discharged). Median of the simplified HOSPITAL score was 3 points
(IQR 2-5). Overall accuracy was very good with a Brier score of 0.08 and
discriminatory power remained good with a C-statistic of 0.69 (95% CI 0.68 to
0.69). The calibration was excellent when comparing the expected with the
observed risk in the two risk categories. CONCLUSIONS: The simplified HOSPITAL
score has good performance for predicting 30-day readmission. Prognostic accuracy
was similar to the original version, while its use is even easier. This
simplified score may provide a good alternative to the original score depending
on the setting.
PMID- 28416653
TI - Can processing demands explain toddlers' performance in false-belief tasks?
PMID- 28416654
TI - Reconstructed ancestral enzymes suggest long-term cooling of Earth's photic zone
since the Archean.
AB - Paleotemperatures inferred from the isotopic compositions (delta18O and
delta30Si) of marine cherts suggest that Earth's oceans cooled from 70 +/- 15
degrees C in the Archean to the present ~15 degrees C. This interpretation,
however, has been subject to question due to uncertainties regarding oceanic
isotopic compositions, diagenetic or metamorphic resetting of the isotopic
record, and depositional environments. Analyses of the thermostability of
reconstructed ancestral enzymes provide an independent method by which to assess
the temperature history inferred from the isotopic evidence. Although previous
studies have demonstrated extreme thermostability in reconstructed archaeal and
bacterial proteins compatible with a hot early Earth, taxa investigated may have
inhabited local thermal environments that differed significantly from average
surface conditions. We here present thermostability measurements of reconstructed
ancestral enzymatically active nucleoside diphosphate kinases (NDKs) derived from
light-requiring prokaryotic and eukaryotic phototrophs having widely separated
fossil-based divergence ages. The ancestral environmental temperatures thereby
determined for these photic-zone organisms--shown in modern taxa to correlate
strongly with NDK thermostability--are inferred to reflect ancient surface
environment paleotemperatures. Our results suggest that Earth's surface
temperature decreased over geological time from ~65-80 degrees C in the Archean,
a finding consistent both with previous isotope-based and protein reconstruction
based interpretations. Interdisciplinary studies such as those reported here
integrating genomic, geologic, and paleontologic data hold promise for providing
new insight into the coevolution of life and environment over Earth history.
PMID- 28416655
TI - Economic inequality increases risk taking.
AB - Rising income inequality is a global trend. Increased income inequality has been
associated with higher rates of crime, greater consumer debt, and poorer health
outcomes. The mechanisms linking inequality to poor outcomes among individuals
are poorly understood. This research tested a behavioral account linking
inequality to individual decision making. In three experiments (n = 811), we
found that higher inequality in the outcomes of an economic game led participants
to take greater risks to try to achieve higher outcomes. This effect of unequal
distributions on risk taking was driven by upward social comparisons. Next, we
estimated economic risk taking in daily life using large-scale data from internet
searches. Risk taking was higher in states with greater income inequality, an
effect driven by inequality at the upper end of the income distribution. Results
suggest that inequality may promote poor outcomes, in part, by increasing risky
behavior.
PMID- 28416656
TI - Effect of cholesterol on the molecular structure and transitions in a clinical
grade lung surfactant extract.
AB - The lipid-protein film covering the interface of the lung alveolar in mammals is
vital for proper lung function and its deficiency is related to a range of
diseases. Here we present a molecular-level characterization of a clinical-grade
porcine lung surfactant extract using a multitechnique approach consisting of
[Formula: see text]-[Formula: see text] solid-state nuclear magnetic
spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The
detailed characterization presented for reconstituted membranes of a lung extract
demonstrates that the molecular structure of lung surfactant strongly depends on
the concentration of cholesterol. If cholesterol makes up about 11% of the total
dry weight of lung surfactant, the surfactant extract adopts a single liquid
ordered lamellar phase, [Formula: see text], at physiological temperatures. This
[Formula: see text] phase gradually changes into a liquid-disordered lamellar
phase, [Formula: see text], when the temperature is increased by a few degrees.
In the absence of cholesterol the system segregates into one lamellar gel phase
and one [Formula: see text] phase. Remarkably, it was possible to measure a large
set of order parameter magnitudes [Formula: see text] from the liquid-disordered
and -ordered lamellar phases and assign them to specific C-H bonds of the
phospholipids in the biological extract with no use of isotopic labeling. These
findings with molecular details on lung surfactant mixtures together with the
presented NMR methodology may guide further development of pulmonary surfactant
pharmaceuticals that better mimic the physiological self-assembly compositions
for treatment of pathological states such as respiratory distress syndrome.
PMID- 28416657
TI - Role of atmospheric oxidation in recent methane growth.
AB - The growth in global methane (CH4) concentration, which had been ongoing since
the industrial revolution, stalled around the year 2000 before resuming globally
in 2007. We evaluate the role of the hydroxyl radical (OH), the major CH4 sink,
in the recent CH4 growth. We also examine the influence of systematic
uncertainties in OH concentrations on CH4 emissions inferred from atmospheric
observations. We use observations of 1,1,1-trichloroethane (CH3CCl3), which is
lost primarily through reaction with OH, to estimate OH levels as well as CH3CC3
emissions, which have uncertainty that previously limited the accuracy of OH
estimates. We find a 64-70% probability that a decline in OH has contributed to
the post-2007 methane rise. Our median solution suggests that CH4 emissions
increased relatively steadily during the late 1990s and early 2000s, after which
growth was more modest. This solution obviates the need for a sudden
statistically significant change in total CH4 emissions around the year 2007 to
explain the atmospheric observations and can explain some of the decline in the
atmospheric 13CH4/12CH4 ratio and the recent growth in C2H6 Our approach
indicates that significant OH-related uncertainties in the CH4 budget remain, and
we find that it is not possible to implicate, with a high degree of confidence,
rapid global CH4 emissions changes as the primary driver of recent trends when
our inferred OH trends and these uncertainties are considered.
PMID- 28416658
TI - Correction to Supporting Information for Falahati and Wieschaus, Independent
active and thermodynamic processes govern the nucleolus assembly in vivo.
PMID- 28416659
TI - Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH
stability.
AB - Hippo signaling controls the expression of genes regulating cell proliferation
and survival and organ size. The regulation of core components in the Hippo
pathway by phosphorylation has been extensively investigated, but the roles of
ubiquitination-deubiquitination processes are largely unknown. To identify
deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA
screening and found that YOD1 controls biological responses mediated by YAP/TAZ.
Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances
the stability of ITCH, which leads to reduced levels of LATS and a subsequent
increase in the YAP/TAZ level. Furthermore, we show that the miR-21-mediated
regulation of YOD1 is responsible for the cell-density-dependent changes in
YAP/TAZ levels. Using a transgenic mouse model, we demonstrate that the inducible
expression of YOD1 enhances the proliferation of hepatocytes and leads to
hepatomegaly in a YAP/TAZ-activity-dependent manner. Moreover, we find a strong
correlation between YOD1 and YAP expression in liver cancer patients. Overall,
our data strongly suggest that YOD1 is a regulator of the Hippo pathway and would
be a therapeutic target to treat liver cancer.
PMID- 28416660
TI - Redefining the essential trafficking pathway for outer membrane lipoproteins.
AB - The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and
an intrinsic antibiotic resistance factor. Lipoproteins are OM components that
function in cell wall synthesis, diverse secretion systems, and antibiotic efflux
pumps. Moreover, each of the essential OM machines that assemble the barrier
requires one or more lipoproteins. This dependence is thought to explain the
essentiality of the periplasmic chaperone LolA and its OM receptor LolB that
traffic lipoproteins to the OM. However, we show that in strains lacking
substrates that are toxic when mislocalized, both LolA and LolB can be completely
bypassed by activating an envelope stress response without compromising
trafficking of essential lipoproteins. We identify the Cpx stress response as a
monitor of lipoprotein trafficking tasked with protecting the cell from
mislocalized lipoproteins. Moreover, our findings reveal that an alternate
trafficking pathway exists that can, under certain conditions, bypass the
functions of LolA and LolB, implying that these proteins do not perform any truly
essential mechanistic steps in lipoprotein trafficking. Instead, these proteins'
key function is to prevent lethal accumulation of mislocalized lipoproteins.
PMID- 28416661
TI - Single-cell analysis of HIV-1 transcriptional activity reveals expression of
proviruses in expanded clones during ART.
AB - Little is known about the fraction of human immunodeficiency virus type 1 (HIV-1)
proviruses that express unspliced viral RNA in vivo or about the levels of HIV
RNA expression within single infected cells. We developed a sensitive cell
associated HIV RNA and DNA single-genome sequencing (CARD-SGS) method to
investigate fractional proviral expression of HIV RNA (1.3-kb fragment of p6,
protease, and reverse transcriptase) and the levels of HIV RNA in single HIV
infected cells from blood samples obtained from individuals with viremia or
individuals on long-term suppressive antiretroviral therapy (ART). Spiking
experiments show that the CARD-SGS method can detect a single cell expressing HIV
RNA. Applying CARD-SGS to blood mononuclear cells in six samples from four HIV
infected donors (one with viremia and not on ART and three with viremia
suppressed on ART) revealed that an average of 7% of proviruses (range: 2-18%)
expressed HIV RNA. Levels of expression varied from one to 62 HIV RNA molecules
per cell (median of 1). CARD-SGS also revealed the frequent expression of
identical HIV RNA sequences across multiple single cells and across multiple time
points in donors on suppressive ART consistent with constitutive expression of
HIV RNA in infected cell clones. Defective proviruses were found to express HIV
RNA at levels similar to those proviruses that had no obvious defects. CARD-SGS
is a useful tool to characterize fractional proviral expression in single
infected cells that persist despite ART and to assess the impact of experimental
interventions on proviral populations and their expression.
PMID- 28416662
TI - Adapt to more wildfire in western North American forests as climate changes.
AB - Wildfires across western North America have increased in number and size over the
past three decades, and this trend will continue in response to further warming.
As a consequence, the wildland-urban interface is projected to experience
substantially higher risk of climate-driven fires in the coming decades. Although
many plants, animals, and ecosystem services benefit from fire, it is unknown how
ecosystems will respond to increased burning and warming. Policy and management
have focused primarily on specified resilience approaches aimed at resistance to
wildfire and restoration of areas burned by wildfire through fire suppression and
fuels management. These strategies are inadequate to address a new era of western
wildfires. In contrast, policies that promote adaptive resilience to wildfire, by
which people and ecosystems adjust and reorganize in response to changing fire
regimes to reduce future vulnerability, are needed. Key aspects of an adaptive
resilience approach are (i) recognizing that fuels reduction cannot alter
regional wildfire trends; (ii) targeting fuels reduction to increase adaptation
by some ecosystems and residential communities to more frequent fire; (iii)
actively managing more wild and prescribed fires with a range of severities; and
(iv) incentivizing and planning residential development to withstand inevitable
wildfire. These strategies represent a shift in policy and management from
restoring ecosystems based on historical baselines to adapting to changing fire
regimes and from unsustainable defense of the wildland-urban interface to
developing fire-adapted communities. We propose an approach that accepts wildfire
as an inevitable catalyst of change and that promotes adaptive responses by
ecosystems and residential communities to more warming and wildfire.
PMID- 28416663
TI - Bistable metamaterial for switching and cascading elastic vibrations.
AB - The realization of acoustic devices analogous to electronic systems, like diodes,
transistors, and logic elements, suggests the potential use of elastic vibrations
(i.e., phonons) in information processing, for example, in advanced computational
systems, smart actuators, and programmable materials. Previous experimental
realizations of acoustic diodes and mechanical switches have used nonlinearities
to break transmission symmetry. However, existing solutions require operation at
different frequencies or involve signal conversion in the electronic or optical
domains. Here, we show an experimental realization of a phononic transistor-like
device using geometric nonlinearities to switch and amplify elastic vibrations,
via magnetic coupling, operating at a single frequency. By cascading this device
in a tunable mechanical circuit board, we realize the complete set of mechanical
logic elements and interconnect selected ones to execute simple calculations.
PMID- 28416664
TI - Three-dimensional stable lithium metal anode with nanoscale lithium islands
embedded in ionically conductive solid matrix.
AB - Rechargeable batteries based on lithium (Li) metal chemistry are attractive for
next-generation electrochemical energy storage. Nevertheless, excessive dendrite
growth, infinite relative dimension change, severe side reactions, and limited
power output severely impede their practical applications. Although exciting
progress has been made to solve parts of the above issues, a versatile solution
is still absent. Here, a Li-ion conductive framework was developed as a stable
"host" and efficient surface protection to address the multifaceted problems,
which is a significant step forward compared with previous host concepts. This
was fulfilled by reacting overstoichiometry of Li with SiO. The as-formed LixSi
Li2O matrix would not only enable constant electrode-level volume, but also
protect the embedded Li from direct exposure to electrolyte. Because uniform Li
nucleation and deposition can be fulfilled owing to the high-density active Li
domains, the as-obtained nanocomposite electrode exhibits low polarization,
stable cycling, and high-power output (up to 10 mA/cm2) even in carbonate
electrolytes. The Li-S prototype cells further exhibited highly improved capacity
retention under high-power operation (~600 mAh/g at 6.69 mA/cm2). The all-around
improvement on electrochemical performance sheds light on the effectiveness of
the design principle for developing safe and stable Li metal anodes.
PMID- 28416665
TI - Hippo pathway mediates resistance to cytotoxic drugs.
AB - Chemotherapy is widely used for cancer treatment, but its effectiveness is
limited by drug resistance. Here, we report a mechanism by which cell density
activates the Hippo pathway, which in turn inactivates YAP, leading to changes in
the regulation of genes that control the intracellular concentrations of
gemcitabine and several other US Food and Drug Administration (FDA)-approved
oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and
human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived
xenograft models. Nuclear YAP enhances gemcitabine effectiveness by down
regulating multidrug transporters as well by converting gemcitabine to a less
active form, both leading to its increased intracellular availability. Cancer
cell lines carrying genetic aberrations that impair the Hippo signaling pathway
showed heightened sensitivity to gemcitabine. These findings suggest that
"switching off" of the Hippo-YAP pathway could help to prevent or reverse
resistance to some cancer therapies.
PMID- 28416666
TI - Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis.
AB - Despite the wide administration of several effective vaccines, rotavirus (RV)
remains the single most important etiological agent of severe diarrhea in infants
and young children worldwide, with an annual mortality of over 200,000 people. RV
attachment and internalization into target cells is mediated by its outer capsid
protein VP4. To better understand the molecular details of RV entry, we performed
tandem affinity purification coupled with high-resolution mass spectrometry to
map the host proteins that interact with VP4. We identified an actin-binding
protein, drebrin (DBN1), that coprecipitates and colocalizes with VP4 during RV
infection. Importantly, blocking DBN1 function by siRNA silencing, CRISPR
knockout (KO), or chemical inhibition significantly increased host cell
susceptibility to RV infection. Dbn1 KO mice exhibited higher incidence of
diarrhea and more viral antigen shedding in their stool samples compared with the
wild-type littermates. In addition, we found that uptake of other dynamin
dependent cargos, including transferrin, cholera toxin, and multiple viruses, was
also enhanced in DBN1-deficient cells. Inhibition of cortactin or dynamin-2
abrogated the increased virus entry observed in DBN1-deficient cells, suggesting
that DBN1 suppresses dynamin-mediated endocytosis via interaction with cortactin.
Our study unveiled an unexpected role of DBN1 in restricting the entry of RV and
other viruses into host cells and more broadly to function as a crucial negative
regulator of diverse dynamin-dependent endocytic pathways.
PMID- 28416667
TI - Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose
monitoring using a fully integrated wearable platform.
AB - Perspiration-based wearable biosensors facilitate continuous monitoring of
individuals' health states with real-time and molecular-level insight. The
inherent inaccessibility of sweat in sedentary individuals in large volume (>=10
uL) for on-demand and in situ analysis has limited our ability to capitalize on
this noninvasive and rich source of information. A wearable and miniaturized
iontophoresis interface is an excellent solution to overcome this barrier. The
iontophoresis process involves delivery of stimulating agonists to the sweat
glands with the aid of an electrical current. The challenge remains in devising
an iontophoresis interface that can extract sufficient amount of sweat for robust
sensing, without electrode corrosion and burning/causing discomfort in subjects.
Here, we overcame this challenge through realizing an electrochemically enhanced
iontophoresis interface, integrated in a wearable sweat analysis platform. This
interface can be programmed to induce sweat with various secretion profiles for
real-time analysis, a capability which can be exploited to advance our knowledge
of the sweat gland physiology and the secretion process. To demonstrate the
clinical value of our platform, human subject studies were performed in the
context of the cystic fibrosis diagnosis and preliminary investigation of the
blood/sweat glucose correlation. With our platform, we detected the elevated
sweat electrolyte content of cystic fibrosis patients compared with that of
healthy control subjects. Furthermore, our results indicate that oral glucose
consumption in the fasting state is followed by increased glucose levels in both
sweat and blood. Our solution opens the possibility for a broad range of
noninvasive diagnostic and general population health monitoring applications.
PMID- 28416668
TI - Ambiguity in the causes for decadal trends in atmospheric methane and hydroxyl.
AB - Methane is the second strongest anthropogenic greenhouse gas and its atmospheric
burden has more than doubled since 1850. Methane concentrations stabilized in the
early 2000s and began increasing again in 2007. Neither the stabilization nor the
recent growth are well understood, as evidenced by multiple competing hypotheses
in recent literature. Here we use a multispecies two-box model inversion to
jointly constrain 36 y of methane sources and sinks, using ground-based
measurements of methane, methyl chloroform, and the C13/C12 ratio in atmospheric
methane (delta13CH4) from 1983 through 2015. We find that the problem, as
currently formulated, is underdetermined and solutions obtained in previous work
are strongly dependent on prior assumptions. Based on our analysis, the
mathematically most likely explanation for the renewed growth in atmospheric
methane, counterintuitively, involves a 25-Tg/y decrease in methane emissions
from 2003 to 2016 that is offset by a 7% decrease in global mean hydroxyl (OH)
concentrations, the primary sink for atmospheric methane, over the same period.
However, we are still able to fit the observations if we assume that OH
concentrations are time invariant (as much of the previous work has assumed) and
we then find solutions that are largely consistent with other proposed hypotheses
for the renewed growth of atmospheric methane since 2007. We conclude that the
current surface observing system does not allow unambiguous attribution of the
decadal trends in methane without robust constraints on OH variability, which
currently rely purely on methyl chloroform data and its uncertain emissions
estimates.
PMID- 28416669
TI - Coding of navigational affordances in the human visual system.
AB - A central component of spatial navigation is determining where one can and cannot
go in the immediate environment. We used fMRI to test the hypothesis that the
human visual system solves this problem by automatically identifying the
navigational affordances of the local scene. Multivoxel pattern analyses showed
that a scene-selective region of dorsal occipitoparietal cortex, known as the
occipital place area, represents pathways for movement in scenes in a manner that
is tolerant to variability in other visual features. These effects were found in
two experiments: One using tightly controlled artificial environments as stimuli,
the other using a diverse set of complex, natural scenes. A reconstruction
analysis demonstrated that the population codes of the occipital place area could
be used to predict the affordances of novel scenes. Taken together, these results
reveal a previously unknown mechanism for perceiving the affordance structure of
navigable space.
PMID- 28416670
TI - Alterations in cellular metabolism triggered by URA7 or GLN3 inactivation cause
imbalanced dNTP pools and increased mutagenesis.
AB - Eukaryotic DNA replication fidelity relies on the concerted action of DNA
polymerase nucleotide selectivity, proofreading activity, and DNA mismatch repair
(MMR). Nucleotide selectivity and proofreading are affected by the balance and
concentration of deoxyribonucleotide (dNTP) pools, which are strictly regulated
by ribonucleotide reductase (RNR). Mutations preventing DNA polymerase
proofreading activity or MMR function cause mutator phenotypes and consequently
increased cancer susceptibility. To identify genes not previously linked to high
fidelity DNA replication, we conducted a genome-wide screen in Saccharomyces
cerevisiae using DNA polymerase active-site mutants as a "sensitized mutator
background." Among the genes identified in our screen, three metabolism-related
genes (GLN3, URA7, and SHM2) have not been previously associated to the
suppression of mutations. Loss of either the transcription factor Gln3 or
inactivation of the CTP synthetase Ura7 both resulted in the activation of the
DNA damage response and imbalanced dNTP pools. Importantly, these dNTP imbalances
are strongly mutagenic in genetic backgrounds where DNA polymerase function or
MMR activity is partially compromised. Previous reports have shown that dNTP pool
imbalances can be caused by mutations altering the allosteric regulation of
enzymes involved in dNTP biosynthesis (e.g., RNR or dCMP deaminase). Here, we
provide evidence that mutations affecting genes involved in RNR substrate
production can cause dNTP imbalances, which cannot be compensated by RNR or other
enzymatic activities. Moreover, Gln3 inactivation links nutrient deprivation to
increased mutagenesis. Our results suggest that similar genetic interactions
could drive mutator phenotypes in cancer cells.
PMID- 28416671
TI - Case for the genetic code as a triplet of triplets.
AB - The efficiency of codon translation in vivo is controlled by many factors,
including codon context. At a site early in the Salmonella flgM gene, the effects
on translation of replacing codons Thr6 and Pro8 of flgM with synonymous
alternates produced a 600-fold range in FlgM activity. Synonymous changes at Thr6
and Leu9 resulted in a twofold range in FlgM activity. The level of FlgM activity
produced by any codon arrangement was directly proportional to the degree of in
vivo ribosome stalling at synonymous codons. Synonymous codon suppressors that
corrected the effect of a translation-defective synonymous flgM allele were
restricted to two codons flanking the translation-defective codon. The various
codon arrangements had no apparent effects on flgM mRNA stability or predicted
mRNA secondary structures. Our data suggest that efficient mRNA translation is
determined by a triplet-of-triplet genetic code. That is, the efficiency of
translating a particular codon is influenced by the nature of the immediately
adjacent flanking codons. A model explains these codon-context effects by
suggesting that codon recognition by elongation factor-bound aminoacyl-tRNA is
initiated by hydrogen bond interactions between the first two nucleotides of the
codon and anticodon and then is stabilized by base-stacking energy over three
successive codons.
PMID- 28416672
TI - Bisulfite-converted duplexes for the strand-specific detection and quantification
of rare mutations.
AB - The identification of mutations that are present at low frequencies in clinical
samples is an essential component of precision medicine. The development of
molecular barcoding for next-generation sequencing has greatly enhanced the
sensitivity of detecting such mutations by massively parallel sequencing.
However, further improvements in specificity would be useful for a variety of
applications. We herein describe a technology (BiSeqS) that can increase the
specificity of sequencing by at least two orders of magnitude over and above that
achieved with molecular barcoding and can be applied to any massively parallel
sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two
strands of molecularly barcoded DNA; its specificity arises from the requirement
for the same mutation to be identified in both strands. Because no library
preparation is required, the technology permits very efficient use of the
template DNA as well as sequence reads, which are nearly all confined to the
amplicons of interest. Such efficiency is critical for clinical samples, such as
plasma, in which only tiny amounts of DNA are often available. We show here that
BiSeqS can be applied to evaluate transversions, as well as small insertions or
deletions, and can reliably detect one mutation among >10,000 wild-type
molecules.
PMID- 28416673
TI - Are there many different routes to becoming a global biodiversity hotspot?
PMID- 28416674
TI - Inducing protein aggregation by extensional flow.
AB - Relative to other extrinsic factors, the effects of hydrodynamic flow fields on
protein stability and conformation remain poorly understood. Flow-induced protein
remodeling and/or aggregation is observed both in Nature and during the large
scale industrial manufacture of proteins. Despite its ubiquity, the relationships
between the type and magnitude of hydrodynamic flow, a protein's structure and
stability, and the resultant aggregation propensity are unclear. Here, we assess
the effects of a defined and quantified flow field dominated by extensional flow
on the aggregation of BSA, beta2-microglobulin (beta2m), granulocyte colony
stimulating factor (G-CSF), and three monoclonal antibodies (mAbs). We show that
the device induces protein aggregation after exposure to an extensional flow
field for 0.36-1.8 ms, at concentrations as low as 0.5 mg mL-1 In addition, we
reveal that the extent of aggregation depends on the applied strain rate and the
concentration, structural scaffold, and sequence of the protein. Finally we
demonstrate the in situ labeling of a buried cysteine residue in BSA during
extensional stress. Together, these data indicate that an extensional flow
readily unfolds thermodynamically and kinetically stable proteins, exposing
previously sequestered sequences whose aggregation propensity determines the
probability and extent of aggregation.
PMID- 28416675
TI - Integrin extension enables ultrasensitive regulation by cytoskeletal force.
AB - Integrins undergo large-scale conformational changes upon activation. Signaling
events driving integrin activation have previously been discussed conceptually,
but not quantitatively. Here, recent measurements of the intrinsic ligand-binding
affinity and free energy of each integrin conformational state on the cell
surface, together with the length scales of conformational change, are used to
quantitatively compare models of activation. We examine whether binding of
cytoskeletal adaptors to integrin cytoplasmic domains is sufficient for
activation or whether exertion of tensile force by the actin cytoskeleton across
the integrin-ligand complex is also required. We find that only the combination
of adaptor binding and cytoskeletal force provides ultrasensitive regulation.
Moreover, switch-like activation by force depends on the large, >130 A length
scale change in integrin extension, which is well tailored to match the free
energy difference between the inactive (bent-closed) and active (extended-open)
conformations. The length scale and energy cost in integrin extension enable
activation by force in the low pN range and appear to be the key specializations
that enable cell adhesion through integrins to be coordinated with cytoskeletal
dynamics.
PMID- 28416676
TI - Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus
in parallel with behavioral outputs.
AB - The temporal order of physiology and behavior in mammals is primarily regulated
by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus
(SCN). Taking advantage of bioluminescence reporters, we monitored the circadian
rhythms of the expression of clock genes Per1 and Bmal1 in the SCN of freely
moving mice and found that the rate of phase shifts induced by a single light
pulse was different in the two rhythms. The Per1-luc rhythm was phase-delayed
instantaneously by the light presented at the subjective evening in parallel with
the activity onset of behavioral rhythm, whereas the Bmal1-ELuc rhythm was phase
delayed gradually, similar to the activity offset. The dissociation was confirmed
in cultured SCN slices of mice carrying both Per1-luc and Bmal1-ELuc reporters.
The two rhythms in a single SCN slice showed significantly different periods in a
long-term (3 wk) culture and were internally desynchronized. Regional specificity
in the SCN was not detected for the period of Per1-luc and Bmal1-ELuc rhythms.
Furthermore, neither is synchronized with circadian intracellular Ca2+ rhythms
monitored by a calcium indicator, GCaMP6s, or with firing rhythms monitored on a
multielectrode array dish, although the coupling between the circadian firing and
Ca2+ rhythms persisted during culture. These findings indicate that the
expressions of two key clock genes, Per1 and Bmal1, in the SCN are regulated in
such a way that they may adopt different phases and free-running periods relative
to each other and are respectively associated with the expression of activity
onset and offset.
PMID- 28416677
TI - Structural toggle in the RNaseH domain of Prp8 helps balance splicing fidelity
and catalytic efficiency.
AB - Pre-mRNA splicing is an essential step of eukaryotic gene expression that
requires both high efficiency and high fidelity. Prp8 has long been considered
the "master regulator" of the spliceosome, the molecular machine that executes
pre-mRNA splicing. Cross-linking and structural studies place the RNaseH domain
(RH) of Prp8 near the spliceosome's catalytic core and demonstrate that prp8
alleles that map to a 17-aa extension in RH stabilize it in one of two mutually
exclusive structures, the biological relevance of which are unknown. We performed
an extensive characterization of prp8 alleles that map to this extension and,
using in vitro and in vivo reporter assays, show they fall into two functional
classes associated with the two structures: those that promote error
prone/efficient splicing and those that promote hyperaccurate/inefficient
splicing. Identification of global locations of endogenous splice-site activation
by lariat sequencing confirms the fidelity effects seen in our reporter assays.
Furthermore, we show that error-prone/efficient RH alleles suppress a prp2 mutant
deficient at promoting the first catalytic step of splicing, whereas
hyperaccurate/inefficient RH alleles exhibit synthetic sickness. Together our
data indicate that prp8 RH alleles link splicing fidelity with catalytic
efficiency by biasing the relative stabilities of distinct spliceosome
conformations. We hypothesize that the spliceosome "toggles" between such error
prone/efficient and hyperaccurate/inefficient conformations during the splicing
cycle to regulate splicing fidelity.
PMID- 28416678
TI - Reply to Rubio-Fernandez et al.: Different traditional false-belief tasks impose
different processing demands for toddlers.
PMID- 28416679
TI - Sensorimotor-independent development of hands and tools selectivity in the visual
cortex.
AB - The visual occipito-temporal cortex is composed of several distinct regions
specialized in the identification of different object kinds such as tools and
bodies. Its organization appears to reflect not only the visual characteristics
of the inputs but also the behavior that can be achieved with them. For example,
there are spatially overlapping responses for viewing hands and tools, which is
likely due to their common role in object-directed actions. How dependent is
occipito-temporal cortex organization on object manipulation and motor
experience? To investigate this question, we studied five individuals born
without hands (individuals with upper limb dysplasia), who use tools with their
feet. Using fMRI, we found the typical selective hand-tool overlap (HTO) not only
in typically developed control participants but also in four of the five
dysplasics. Functional connectivity of the HTO in the dysplasics also showed a
largely similar pattern as in the controls. The preservation of functional
organization in the dysplasics suggests that occipito-temporal cortex
specialization is driven largely by inherited connectivity constraints that do
not require sensorimotor experience. These findings complement discoveries of
intact functional organization of the occipito-temporal cortex in people born
blind, supporting an organization largely independent of any one specific sensory
or motor experience.
PMID- 28416681
TI - Correction for Mann, Core Concept: Unraveling the enigma of fast radio bursts.
PMID- 28416680
TI - Using microsecond single-molecule FRET to determine the assembly pathways of T4
ssDNA binding protein onto model DNA replication forks.
AB - DNA replication is a core biological process that occurs in prokaryotic cells at
high speeds (~1 nucleotide residue added per millisecond) and with high fidelity
(fewer than one misincorporation event per 107 nucleotide additions). The ssDNA
binding protein [gene product 32 (gp32)] of the T4 bacteriophage is a central
integrating component of the replication complex that must continuously bind to
and unbind from transiently exposed template strands during DNA synthesis. We
here report microsecond single-molecule FRET (smFRET) measurements on Cy3/Cy5
labeled primer-template (p/t) DNA constructs in the presence of gp32. These
measurements probe the distance between Cy3/Cy5 fluorophores that label the ends
of a short (15-nt) segment of ssDNA attached to a model p/t DNA construct and
permit us to track the stochastic interconversion between various protein bound
and unbound states. The length of the 15-nt ssDNA lattice is sufficient to
accommodate up to two cooperatively bound gp32 proteins in either of two
positions. We apply a unique multipoint time correlation function analysis to the
microsecond-resolved smFRET data obtained to determine and compare the kinetics
of various possible reaction pathways for the assembly of cooperatively bound
gp32 protein onto ssDNA sequences located at the replication fork. The results of
our analysis reveal the presence and translocation mechanisms of short-lived
intermediate bound states that are likely to play a critical role in the assembly
mechanisms of ssDNA binding proteins at replication forks and other ss duplex
junctions.
PMID- 28416682
TI - Computational modeling of epiphany learning.
AB - Models of reinforcement learning (RL) are prevalent in the decision-making
literature, but not all behavior seems to conform to the gradual convergence that
is a central feature of RL. In some cases learning seems to happen all at once.
Limited prior research on these "epiphanies" has shown evidence of sudden changes
in behavior, but it remains unclear how such epiphanies occur. We propose a
sequential-sampling model of epiphany learning (EL) and test it using an eye
tracking experiment. In the experiment, subjects repeatedly play a strategic game
that has an optimal strategy. Subjects can learn over time from feedback but are
also allowed to commit to a strategy at any time, eliminating all other options
and opportunities to learn. We find that the EL model is consistent with the
choices, eye movements, and pupillary responses of subjects who commit to the
optimal strategy (correct epiphany) but not always of those who commit to a
suboptimal strategy or who do not commit at all. Our findings suggest that EL is
driven by a latent evidence accumulation process that can be revealed with eye
tracking data.
PMID- 28416683
TI - Structure and mechanics of aegagropilae fiber network.
AB - Fiber networks encompass a wide range of natural and manmade materials. The
threads or filaments from which they are formed span a wide range of length
scales: from nanometers, as in biological tissues and bundles of carbon
nanotubes, to millimeters, as in paper and insulation materials. The mechanical
and thermal behavior of these complex structures depends on both the individual
response of the constituent fibers and the density and degree of entanglement of
the network. A question of paramount importance is how to control the formation
of a given fiber network to optimize a desired function. The study of fiber
clustering of natural flocs could be useful for improving fabrication processes,
such as in the paper and textile industries. Here, we use the example of
aegagropilae that are the remains of a seagrass (Posidonia oceanica) found on
Mediterranean beaches. First, we characterize different aspects of their
structure and mechanical response, and second, we draw conclusions on their
formation process. We show that these natural aggregates are formed in open sea
by random aggregation and compaction of fibers held together by friction forces.
Although formed in a natural environment, thus under relatively unconstrained
conditions, the geometrical and mechanical properties of the resulting fiber
aggregates are quite robust. This study opens perspectives for manufacturing
complex fiber network materials.
PMID- 28416684
TI - Discovery of chemoautotrophic symbiosis in the giant shipworm Kuphus polythalamia
(Bivalvia: Teredinidae) extends wooden-steps theory.
AB - The "wooden-steps" hypothesis [Distel DL, et al. (2000) Nature 403:725-726]
proposed that large chemosynthetic mussels found at deep-sea hydrothermal vents
descend from much smaller species associated with sunken wood and other organic
deposits, and that the endosymbionts of these progenitors made use of hydrogen
sulfide from biogenic sources (e.g., decaying wood) rather than from vent fluids.
Here, we show that wood has served not only as a stepping stone between habitats
but also as a bridge between heterotrophic and chemoautotrophic symbiosis for the
giant mud-boring bivalve Kuphus polythalamia This rare and enigmatic species,
which achieves the greatest length of any extant bivalve, is the only described
member of the wood-boring bivalve family Teredinidae (shipworms) that burrows in
marine sediments rather than wood. We show that K. polythalamia harbors sulfur
oxidizing chemoautotrophic (thioautotrophic) bacteria instead of the cellulolytic
symbionts that allow other shipworm species to consume wood as food. The
characteristics of its symbionts, its phylogenetic position within Teredinidae,
the reduction of its digestive system by comparison with other family members,
and the loss of morphological features associated with wood digestion indicate
that K. polythalamia is a chemoautotrophic bivalve descended from wood-feeding
(xylotrophic) ancestors. This is an example in which a chemoautotrophic
endosymbiosis arose by displacement of an ancestral heterotrophic symbiosis and a
report of pure culture of a thioautotrophic endosymbiont.
PMID- 28416685
TI - SNAT7 is the primary lysosomal glutamine exporter required for extracellular
protein-dependent growth of cancer cells.
AB - Lysosomes degrade cellular components sequestered by autophagy or extracellular
material internalized by endocytosis and phagocytosis. The macromolecule building
blocks released by lysosomal hydrolysis are then exported to the cytosol by
lysosomal transporters, which remain undercharacterized. In this study, we
designed an in situ assay of lysosomal amino acid export based on the
transcription factor EB (TFEB), a master regulator of lysosomal biogenesis that
detects lysosomal storage. This assay was used to screen candidate lysosomal
transporters, leading to the identification of sodium-coupled neutral amino acid
transporter 7 (SNAT7), encoded by the SLC38A7 gene, as a lysosomal transporter
highly selective for glutamine and asparagine. Cell fractionation confirmed the
lysosomal localization of SNAT7, and flux measurements confirmed its substrate
selectivity and showed a strong activation by the lysosomal pH gradient.
Interestingly, gene silencing or editing experiments revealed that SNAT7 is the
primary permeation pathway for glutamine across the lysosomal membrane and it is
required for growth of cancer cells in a low free-glutamine environment, when
macropinocytosis and lysosomal degradation of extracellular proteins are used as
an alternative source of amino acids. SNAT7 may, thus, represent a novel target
for glutamine-related anticancer therapies.
PMID- 28416686
TI - NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to
mechanical loads in mice.
AB - Sensory nerves emanating from the dorsal root extensively innervate the surfaces
of mammalian bone, a privileged location for the regulation of biomechanical
signaling. Here, we show that NGF-TrkA signaling in skeletal sensory nerves is an
early response to mechanical loading of bone and is required to achieve maximal
load-induced bone formation. First, the elimination of TrkA signaling in mice
harboring mutant TrkAF592A alleles was found to greatly attenuate load-induced
bone formation induced by axial forelimb compression. Next, both in vivo
mechanical loading and in vitro mechanical stretch were shown to induce the
profound up-regulation of NGF in osteoblasts within 1 h of loading. Furthermore,
inhibition of TrkA signaling following axial forelimb compression was observed to
reduce measures of Wnt/beta-catenin activity in osteocytes in the loaded bone.
Finally, the administration of exogenous NGF to wild-type mice was found to
significantly increase load-induced bone formation and Wnt/beta-catenin activity
in osteocytes. In summary, these findings demonstrate that communication between
osteoblasts and sensory nerves through NGF-TrkA signaling is essential for load
induced bone formation in mice.
PMID- 28416687
TI - Structural and functional innovations in the real-time evolution of new
(betaalpha)8 barrel enzymes.
AB - New genes can arise by duplication and divergence, but there is a fundamental gap
in our understanding of the relationship between these genes, the evolving
proteins they encode, and the fitness of the organism. Here we used
crystallography, NMR dynamics, kinetics, and mass spectrometry to explain the
molecular innovations that arose during a previous real-time evolution
experiment. In that experiment, the (betaalpha)8 barrel enzyme HisA was under
selection for two functions (HisA and TrpF), resulting in duplication and
divergence of the hisA gene to encode TrpF specialists, HisA specialists, and
bifunctional generalists. We found that selection affects enzyme structure and
dynamics, and thus substrate preference, simultaneously and sequentially.
Bifunctionality is associated with two distinct sets of loop conformations, each
essential for one function. We observed two mechanisms for functional
specialization: structural stabilization of each loop conformation and substrate
specific adaptation of the active site. Intracellular enzyme performance,
calculated as the product of catalytic efficiency and relative expression level,
was not linearly related to fitness. Instead, we observed thresholds for each
activity above which further improvements in catalytic efficiency had little if
any effect on growth rate. Overall, we have shown how beneficial substitutions
selected during real-time evolution can lead to manifold changes in enzyme
function and bacterial fitness. This work emphasizes the speed at which adaptive
evolution can yield enzymes with sufficiently high activities such that they no
longer limit the growth of their host organism, and confirms the (betaalpha)8
barrel as an inherently evolvable protein scaffold.
PMID- 28416688
TI - Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK
channels in secretory epithelial cells.
AB - Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory gamma1
subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that
contain LRRC26 subunits are active near normal resting potentials even without
Ca2+, suggesting they play unique physiological roles, likely limited to very
specific cell types and cellular functions. By using Lrrc26 KO mice with a beta
gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells,
especially acinar epithelial cells in lacrimal and salivary glands, and also
goblet and Paneth cells in intestine and colon, although absent from neurons. We
establish the presence of LRRC26 protein in eight secretory tissues or tissues
with significant secretory epithelium and show that LRRC26 protein coassembles
with the pore-forming BK alpha-subunit in at least three tissues: lacrimal gland,
parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar
cells, LRRC26 KO shifts BK gating to be like alpha-subunit-only BK channels.
Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva.
LRRC26-containing BK channels are competent to contribute to resting K+ efflux at
normal cell membrane potentials with resting cytosolic Ca2+ concentrations and
likely play a critical physiological role in supporting normal secretory function
in all secretory epithelial cells.
PMID- 28416689
TI - Contractile and chiral activities codetermine the helicity of swimming droplet
trajectories.
AB - Active fluids are a class of nonequilibrium systems where energy is injected into
the system continuously by the constituent particles themselves. Many examples,
such as bacterial suspensions and actomyosin networks, are intrinsically chiral
at a local scale, so that their activity involves torque dipoles alongside the
force dipoles usually considered. Although many aspects of active fluids have
been studied, the effects of chirality on them are much less known. Here, we
study by computer simulation the dynamics of an unstructured droplet of chiral
active fluid in three dimensions. Our model considers only the simplest possible
combination of chiral and achiral active stresses, yet this leads to an
unprecedented range of complex motilities, including oscillatory swimming,
helical swimming, and run-and-tumble motion. Strikingly, whereas the chirality of
helical swimming is the same as the microscopic chirality of torque dipoles in
one regime, the two are opposite in another. Some of the features of these
motility modes resemble those of some single-celled protozoa, suggesting that
underlying mechanisms may be shared by some biological systems and synthetic
active droplets.
PMID- 28416690
TI - Correction for Padilla et al., AgRP to Kiss1 neuron signaling links nutritional
state and fertility.
PMID- 28416691
TI - Neurophysiological dynamics of phrase-structure building during sentence
processing.
AB - Although sentences unfold sequentially, one word at a time, most linguistic
theories propose that their underlying syntactic structure involves a tree of
nested phrases rather than a linear sequence of words. Whether and how the brain
builds such structures, however, remains largely unknown. Here, we used human
intracranial recordings and visual word-by-word presentation of sentences and
word lists to investigate how left-hemispheric brain activity varies during the
formation of phrase structures. In a broad set of language-related areas,
comprising multiple superior temporal and inferior frontal sites, high-gamma
power increased with each successive word in a sentence but decreased suddenly
whenever words could be merged into a phrase. Regression analyses showed that
each additional word or multiword phrase contributed a similar amount of
additional brain activity, providing evidence for a merge operation that applies
equally to linguistic objects of arbitrary complexity. More superficial models of
language, based solely on sequential transition probability over lexical and
syntactic categories, only captured activity in the posterior middle temporal
gyrus. Formal model comparison indicated that the model of multiword phrase
construction provided a better fit than probability-based models at most sites in
superior temporal and inferior frontal cortices. Activity in those regions was
consistent with a neural implementation of a bottom-up or left-corner parser of
the incoming language stream. Our results provide initial intracranial evidence
for the neurophysiological reality of the merge operation postulated by linguists
and suggest that the brain compresses syntactically well-formed sequences of
words into a hierarchy of nested phrases.
PMID- 28416693
TI - Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland
cells.
AB - The Venus flytrap Dionaea muscipula captures insects and consumes their flesh.
Prey contacting touch-sensitive hairs trigger traveling electrical waves. These
action potentials (APs) cause rapid closure of the trap and activate secretory
functions of glands, which cover its inner surface. Such prey-induced
haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling
pathway, which initiates secretion of an acidic hydrolase mixture to decompose
the victim and acquire the animal nutrients. Although postulated since Darwin's
pioneering studies, these secretory events have not been recorded so far. Using
advanced analytical and imaging techniques, such as vibrating ion-selective
electrodes, carbon fiber amperometry, and magnetic resonance imaging, we
monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair
bending or direct application of JA caused a quantal release of oxidizable
material from gland cells monitored as distinct amperometric spikes. Spikes
reminiscent of exocytotic events in secretory animal cells progressively
increased in frequency, reaching steady state 1 d after stimulation. Our data
indicate that trigger-hair mechanical stimulation evokes APs. Gland cells
translate APs into touch-inducible JA signaling that promotes the formation of
secretory vesicles. Early vesicles loaded with H+ and Cl- fuse with the plasma
membrane, hyperacidifying the "green stomach"-like digestive organ, whereas
subsequent ones carry hydrolases and nutrient transporters, together with a
glutathione redox moiety, which is likely to act as the major detected compound
in amperometry. Hence, when glands perceive the haptoelectrical stimulation,
secretory vesicles are tailored to be released in a sequence that optimizes
digestion of the captured animal.
PMID- 28416692
TI - Immunomodulation-accelerated neuronal regeneration following selective rod
photoreceptor cell ablation in the zebrafish retina.
AB - Muller glia (MG) function as inducible retinal stem cells in zebrafish,
completely repairing the eye after damage. The innate immune system has recently
been shown to promote tissue regeneration in which classic wound-healing
responses predominate. However, regulatory roles for leukocytes during cellular
regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are
less well defined. To investigate possible roles innate immune cells play during
retinal cell regeneration, we used intravital microscopy to visualize neutrophil,
macrophage, and retinal microglia responses to induced rod photoreceptor
apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral
macrophage cells responded to rod cell loss, as evidenced by morphological
transitions and increased migration, but did not enter the retina. Retinal
microglia displayed multiple hallmarks of immune cell activation: increased
migration, translocation to the photoreceptor cell layer, proliferation, and
phagocytosis of dying cells. To test function during rod cell regeneration, we
coablated microglia and rod cells or applied immune suppression and quantified
the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation,
and (iii) rod cell replacement. Coablation and immune suppressants applied before
cell loss caused delays in MG/progenitor proliferation rates and slowed the rate
of rod cell replacement. Conversely, immune suppressants applied after cell loss
had been initiated led to accelerated photoreceptor regeneration kinetics,
possibly by promoting rapid resolution of an acute immune response. Our findings
suggest that microglia control MG responsiveness to photoreceptor loss and
support the development of immune-targeted therapeutic strategies for reversing
cell loss associated with degenerative retinal conditions.
PMID- 28416694
TI - Experimental dispersal reveals characteristic scales of biodiversity in a natural
landscape.
AB - Ecological theory posits that dispersal among habitat patches links local
communities and is a key "regional" process that maintains biological diversity.
However, manipulations required to experimentally test regional processes are
infeasible for most systems, and thus more work is needed to detect the scales at
which regional processes manifest and their overall effect on diversity. In a
Californian grassland, a hotspot for global biodiversity, we used a seed vacuum
to increase dispersal at spatial scales varying from 1 m to 10 km while
maintaining a realistic spatial structure of species pools and environmental
conditions. We found that dispersal limitation has a profound influence on
diversity; species richness increased with the spatial scale of seed mixing,
doubling in plots that received seed from large (>=5 km) compared with small (<=5
m) scales. This increase in diversity corresponded to an increase in how well
species distributions were explained by environmental conditions, from modest at
small scales (R2 = 0.34) to strong at large scales (R2 = 0.52). Responses to the
spatial scale of seed mixing were nonlinear, with no differences below 5 m or
above 5 km. Nonlinearities were explained by homogeneity of environmental
conditions below 5 m and by a lack of additional variation in the species pool
above 5 km. Our approach of manipulating natural communities at different spatial
scales reveals (i) nonlinear transitions in the importance of environmental
sorting and dispersal, and (ii) the negative effects of dispersal limitation on
local diversity, consistent with previous research suggesting that large numbers
of species are headed toward regional extinction.
PMID- 28416695
TI - Peter C. Nowell (1928-2016).
PMID- 28416696
TI - Zeaxanthin-dependent nonphotochemical quenching does not occur in photosystem I
in the higher plant Arabidopsis thaliana.
AB - Nonphotochemical quenching (NPQ) is the process that protects the photosynthetic
apparatus of plants and algae from photodamage by dissipating as heat the energy
absorbed in excess. Studies on NPQ have almost exclusively focused on photosystem
II (PSII), as it was believed that NPQ does not occur in photosystem I (PSI).
Recently, Ballottari et al. [Ballottari M, et al. (2014) Proc Natl Acad Sci USA
111:E2431-E2438], analyzing PSI particles isolated from an Arabidopsis thaliana
mutant that accumulates zeaxanthin constitutively, have reported that this
xanthophyll can efficiently induce chlorophyll fluorescence quenching in PSI. In
this work, we have checked the biological relevance of this finding by analyzing
WT plants under high-light stress conditions. By performing time-resolved
fluorescence measurements on PSI isolated from Arabidopsis thaliana WT in dark
adapted and high-light-stressed (NPQ) states, we find that the fluorescence
kinetics of both PSI are nearly identical. To validate this result in vivo, we
have measured the kinetics of PSI directly on leaves in unquenched and NPQ
states; again, no differences were observed. It is concluded that PSI does not
undergo NPQ in biologically relevant conditions in Arabidopsis thaliana The
possible role of zeaxanthin in PSI photoprotection is discussed.
PMID- 28416697
TI - Small molecule-mediated inhibition of myofibroblast transdifferentiation for the
treatment of fibrosis.
AB - Fibrosis, a disease in which excessive amounts of connective tissue accumulate in
response to physical damage and/or inflammatory insult, affects nearly every
tissue in the body and can progress to a state of organ malfunction and death. A
hallmark of fibrotic disease is the excessive accumulation of extracellular
matrix-secreting activated myofibroblasts (MFBs) in place of functional
parenchymal cells. As such, the identification of agents that selectively inhibit
the transdifferentiation process leading to the formation of MFBs represents an
attractive approach for the treatment of diverse fibrosis-related diseases.
Herein we report the development of a high throughput image-based screen using
primary hepatic stellate cells that identified the antifungal drug itraconazole
(ITA) as an inhibitor of MFB cell fate in resident fibroblasts derived from
multiple murine and human tissues (i.e., lung, liver, heart, and skin). Chemical
optimization of ITA led to a molecule (CBR-096-4) devoid of antifungal and human
cytochrome P450 inhibitory activity with excellent pharmacokinetics, safety, and
efficacy in rodent models of lung, liver, and skin fibrosis. These findings may
serve to provide a strategy for the safe and effective treatment of a broad range
of fibrosis-related diseases.
PMID- 28416698
TI - Selective in vivo removal of pathogenic anti-MAG autoantibodies, an antigen
specific treatment option for anti-MAG neuropathy.
AB - Anti-MAG (myelin-associated glycoprotein) neuropathy is a disabling autoimmune
peripheral neuropathy caused by monoclonal IgM autoantibodies that recognize the
carbohydrate epitope HNK-1 (human natural killer-1). This glycoepitope is highly
expressed on adhesion molecules, such as MAG, present in myelinated nerve fibers.
Because the pathogenicity and demyelinating properties of anti-MAG autoantibodies
are well established, current treatments are aimed at reducing autoantibody
levels. However, current therapies are primarily immunosuppressive and lack
selectivity and efficacy. We therefore hypothesized that a significant
improvement in the disease condition could be achieved by selectively
neutralizing the pathogenic anti-MAG antibodies with carbohydrate-based ligands
mimicking the natural HNK-1 glycoepitope 1. In an inhibition assay, a mimetic (2,
mimHNK-1) of the natural HNK-1 epitope blocked the interaction of MAG with
pathogenic IgM antibodies from patient sera but with only micromolar affinity.
Therefore, considering the multivalent nature of the MAG-IgM interaction,
polylysine polymers of different sizes were substituted with mimetic 2. With the
most promising polylysine glycopolymer PL84(mimHNK-1)45 the inhibitory effect on
patient sera could be improved by a factor of up to 230,000 per epitope,
consequently leading to a low-nanomolar inhibitory potency. Because clinical
studies indicate a correlation between the reduction of anti-MAG IgM levels and
clinical improvement, an immunological surrogate mouse model for anti-MAG
neuropathy producing high levels of anti-MAG IgM was developed. The observed
efficient removal of these antibodies with the glycopolymer PL84(mimHNK-1)45
represents an important step toward an antigen-specific therapy for anti-MAG
neuropathy.
PMID- 28416699
TI - IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X
ray crystallography.
AB - The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion
channel that releases calcium ions (Ca2+) from the endoplasmic reticulum. The IP3
binding sites in the large cytosolic domain are distant from the Ca2+ conducting
pore, and the allosteric mechanism of how IP3 opens the Ca2+ channel remains
elusive. Here, we identify a long-range gating mechanism uncovered by channel
mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type
1 IP3R in the absence and presence of IP3 Analyses of two distinct space group
crystals uncovered an IP3-dependent global translocation of the curvature alpha
helical domain interfacing with the cytosolic and channel domains. Mutagenesis of
the IP3R channel revealed an essential role of a leaflet structure in the alpha
helical domain. These results suggest that the curvature alpha-helical domain
relays IP3-controlled global conformational dynamics to the channel through the
leaflet, conferring long-range allosteric coupling from IP3 binding to the Ca2+
channel.
PMID- 28416700
TI - Intensifying postfire weather and biological invasion drive species loss in a
Mediterranean-type biodiversity hotspot.
AB - Prolonged periods of extreme heat or drought in the first year after fire affect
the resilience and diversity of fire-dependent ecosystems by inhibiting seed
germination or increasing mortality of seedlings and resprouting individuals.
This interaction between weather and fire is of growing concern as climate
changes, particularly in systems subject to stand-replacing crown fires, such as
most Mediterranean-type ecosystems. We examined the longest running set of
permanent vegetation plots in the Fynbos of South Africa (44 y), finding a
significant decline in the diversity of plots driven by increasingly severe
postfire summer weather events (number of consecutive days with high temperatures
and no rain) and legacy effects of historical woody alien plant densities 30 y
after clearing. Species that resprout after fire and/or have graminoid or herb
growth forms were particularly affected by postfire weather, whereas all species
were sensitive to invasive plants. Observed differences in the response of
functional types to extreme postfire weather could drive major shifts in
ecosystem structure and function such as altered fire behavior, hydrology, and
carbon storage. An estimated 0.5 degrees C increase in maximum temperature
tolerance of the species sets unique to each survey further suggests selection
for species adapted to hotter conditions. Taken together, our results show
climate change impacts on biodiversity in the hyperdiverse Cape Floristic Region
and demonstrate an important interaction between extreme weather and disturbance
by fire that may make flammable ecosystems particularly sensitive to climate
change.
PMID- 28416702
TI - Massive horizontal transfer of transposable elements in insects.
AB - Horizontal transfer (HT) of genetic material is central to the architecture and
evolution of prokaryote genomes. Within eukaryotes, the majority of HTs reported
so far are transfers of transposable elements (TEs). These reports essentially
come from studies focusing on specific lineages or types of TEs. Because of the
lack of large-scale survey, the amount and impact of HT of TEs (HTT) in eukaryote
evolution, as well as the trends and factors shaping these transfers, are poorly
known. Here, we report a comprehensive analysis of HTT in 195 insect genomes,
representing 123 genera and 13 of the 28 insect orders. We found that these
insects were involved in at least 2,248 HTT events that essentially occurred
during the last 10 My. We show that DNA transposons transfer horizontally more
often than retrotransposons, and unveil phylogenetic relatedness and geographical
proximity as major factors facilitating HTT in insects. Even though our study is
restricted to a small fraction of insect biodiversity and to a recent
evolutionary timeframe, the TEs we found to be horizontally transferred generated
up to 24% (2.08% on average) of all nucleotides of insect genomes. Together, our
results establish HTT as a major force shaping insect genome evolution.
PMID- 28416701
TI - Defective synaptic connectivity and axonal neuropathology in a human iPSC-based
model of familial Parkinson's disease.
AB - alpha-Synuclein (alphaSyn) is the major gene linked to sporadic Parkinson's
disease (PD), whereas the G209A (p.A53T) alphaSyn mutation causes a familial form
of PD characterized by early onset and a generally severe phenotype, including
nonmotor manifestations. Here we generated de novo induced pluripotent stem cells
(iPSCs) from patients harboring the p.A53T mutation and developed a robust model
that captures PD pathogenic processes under basal conditions. iPSC-derived mutant
neurons displayed novel disease-relevant phenotypes, including protein
aggregation, compromised neuritic outgrowth, and contorted or fragmented axons
with swollen varicosities containing alphaSyn and Tau. The identified
neuropathological features closely resembled those in brains of p.A53T patients.
Small molecules targeting alphaSyn reverted the degenerative phenotype under both
basal and induced stress conditions, indicating a treatment strategy for PD and
other synucleinopathies. Furthermore, mutant neurons showed disrupted synaptic
connectivity and widespread transcriptional alterations in genes involved in
synaptic signaling, a number of which have been previously linked to mental
disorders, raising intriguing implications for potentially converging disease
mechanisms.
PMID- 28416703
TI - On the Evolutionary Origin of CAM Photosynthesis.
PMID- 28416704
TI - Diurnal Variation in Gas Exchange: The Balance between Carbon Fixation and Water
Loss.
AB - Stomatal control of transpiration is critical for maintaining important
processes, such as plant water status, leaf temperature, as well as permitting
sufficient CO2 diffusion into the leaf to maintain photosynthetic rates (A).
Stomatal conductance often closely correlates with A and is thought to control
the balance between water loss and carbon gain. It has been suggested that a
mesophyll-driven signal coordinates A and stomatal conductance responses to
maintain this relationship; however, the signal has yet to be fully elucidated.
Despite this correlation under stable environmental conditions, the responses of
both parameters vary spatially and temporally and are dependent on species,
environment, and plant water status. Most current models neglect these aspects of
gas exchange, although it is clear that they play a vital role in the balance of
carbon fixation and water loss. Future efforts should consider the dynamic nature
of whole-plant gas exchange and how it represents much more than the sum of its
individual leaf-level components, and they should take into consideration the
long-term effect on gas exchange over time.
PMID- 28416705
TI - Defining the Diverse Cell Populations Contributing to Lignification in
Arabidopsis Stems.
AB - Many land plants evolved tall and sturdy growth habits due to specialized cells
with thick lignified cell walls: tracheary elements that function in water
transport and fibers that function in structural support. The objective of this
study was to define how and when diverse cell populations contribute lignin
precursors, monolignols, to secondary cell walls during lignification of the
Arabidopsis (Arabidopsis thaliana) inflorescence stem. Previous work demonstrated
that, when lignin biosynthesis is suppressed in fiber and tracheary element cells
with thickened walls, fibers become lignin-depleted while vascular bundles still
lignify, suggesting that nonlignifying neighboring xylem cells are contributing
to lignification. In this work, we dissect the contributions of different cell
types, specifically xylary parenchyma and fiber cells, to lignification of the
stem using cell-type-specific promoters to either knock down an essential
monolignol biosynthetic gene or to introduce novel monolignol conjugates.
Analysis of either reductions in lignin in knockdown lines, or the addition of
novel monolignol conjugates, directly identifies the xylary parenchyma and fiber
cell populations that contribute to the stem lignification and the developmental
timing at which each contribution is most important.
PMID- 28416706
TI - The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for
Viability of Thermococcus kodakarensis.
AB - Many aspects of and factors required for DNA replication are conserved across all
three domains of life, but there are some significant differences surrounding
lagging-strand synthesis. In Archaea, a 5'-to-3' exonuclease, related to both
bacterial RecJ and eukaryotic Cdc45, that associates with the replisome
specifically through interactions with GINS was identified and designated GAN
(for GINS-associated nuclease). Despite the presence of a well-characterized flap
endonuclease (Fen1), it was hypothesized that GAN might participate in primer
removal during Okazaki fragment maturation, and as a Cdc45 homologue, GAN might
also be a structural component of an archaeal CMG (Cdc45, MCM, and GINS)
replication complex. We demonstrate here that, individually, either Fen1 or GAN
can be deleted, with no discernible effects on viability and growth. However,
deletion of both Fen1 and GAN was not possible, consistent with both enzymes
catalyzing the same step in primer removal from Okazaki fragments in vivo RNase
HII has also been proposed to participate in primer processing during Okazaki
fragment maturation. Strains with both Fen1 and RNase HII deleted grew well. GAN
activity is therefore sufficient for viability in the absence of both RNase HII
and Fen1, but it was not possible to construct a strain with both RNase HII and
GAN deleted. Fen1 alone is therefore insufficient for viability in the absence of
both RNase HII and GAN. The ability to delete GAN demonstrates that GAN is not
required for the activation or stability of the archaeal MCM replicative
helicase.IMPORTANCE The mechanisms used to remove primer sequences from Okazaki
fragments during lagging-strand DNA replication differ in the biological domains.
Bacteria use the exonuclease activity of DNA polymerase I, whereas eukaryotes and
archaea encode a flap endonuclease (Fen1) that cleaves displaced primer
sequences. RNase HII and the GINS-associated exonuclease GAN have also been
hypothesized to assist in primer removal in Archaea Here we demonstrate that in
Thermococcus kodakarensis, either Fen1 or GAN activity is sufficient for
viability. Furthermore, GAN can support growth in the absence of both Fen1 and
RNase HII, but Fen1 and RNase HII are required for viability in the absence of
GAN.
PMID- 28416707
TI - Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in
Azospirillum brasilense Sp7.
AB - Chemotaxis is the movement of cells in response to gradients of diverse chemical
cues. Motile bacteria utilize a conserved chemotaxis signal transduction system
to bias their motility and navigate through a gradient. A central regulator of
chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with
membrane-bound receptors, which assemble into large polar arrays, to propagate
the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls
transient increases in swimming speed during chemotaxis, but it also biases the
cell length at division. However, the exact underlying molecular mechanisms for
Che1-dependent control of multiple cellular behaviors are not known. Here, we
identify specific domains of the CheA1 histidine kinase implicated in modulating
each of these functions. We show that CheA1 is produced in two isoforms: a
membrane-anchored isoform produced as a fusion with a conserved seven
transmembrane domain of unknown function (TMX) at the N terminus and a soluble
isoform similar to prototypical CheA. Site-directed and deletion mutagenesis
combined with behavioral assays confirm the role of CheA1 in chemotaxis and
implicate the TMX domain in mediating changes in cell length. Fluorescence
microscopy further reveals that the membrane-anchored isoform is distributed
around the cell surface while the soluble isoform localizes at the cell poles.
Together, the data provide a mechanism for the role of Che1 in controlling
multiple unrelated cellular behaviors via acquisition of a new domain in CheA1
and production of distinct functional isoforms.IMPORTANCE Chemotaxis provides a
significant competitive advantage to bacteria in the environment, and this
function has been transferred laterally multiple times, with evidence of
functional divergence in different genomic contexts. The molecular principles
that underlie functional diversification of chemotaxis in various genomic
contexts are unknown. Here, we provide a molecular mechanism by which a single
CheA protein controls two unrelated functions: chemotaxis and cell length.
Acquisition of this multifunctionality is seemingly a recent evolutionary event.
The findings illustrate a mechanism by which chemotaxis function may be co-opted
to regulate additional cellular functions.
PMID- 28416708
TI - PhoU Allows Rapid Adaptation to High Phosphate Concentrations by Modulating
PstSCAB Transport Rate in Sinorhizobium meliloti.
AB - Maintenance of cellular phosphate homeostasis is essential for cellular life. The
PhoU protein has emerged as a key regulator of this process in bacteria, and it
is suggested to modulate phosphate import by PstSCAB and control activation of
the phosphate limitation response by the PhoR-PhoB two-component system. However,
a proper understanding of PhoU has remained elusive due to numerous complications
of mutating phoU, including loss of viability and the genetic instability of the
mutants. Here, we developed two sets of strains of Sinorhizobium meliloti that
overcame these limitations and allowed a more detailed and comprehensive analysis
of the biological and molecular activities of PhoU. The data showed that phoU
cannot be deleted in the presence of phosphate unless PstSCAB is inactivated
also. However, phoU deletions were readily recovered in phosphate-free media, and
characterization of these mutants revealed that addition of phosphate to the
environment resulted in toxic levels of PstSCAB-mediated phosphate accumulation.
Phosphate uptake experiments indicated that PhoU significantly decreased the
PstSCAB transport rate specifically in phosphate-replete cells but not in
phosphate-starved cells and that PhoU could rapidly respond to elevated
environmental phosphate concentrations and decrease the PstSCAB transport rate.
Site-directed mutagenesis results suggested that the ability of PhoU to respond
to phosphate levels was independent of the conformation of the PstSCAB
transporter. Additionally, PhoU-PhoU and PhoU-PhoR interactions were detected
using a bacterial two-hybrid screen. We propose that PhoU modulates PstSCAB and
PhoR-PhoB in response to local, internal fluctuations in phosphate concentrations
resulting from PstSCAB-mediated phosphate import.IMPORTANCE Correct maintenance
of cellular phosphate homeostasis is critical in all kingdoms of life and in
bacteria involves the PhoU protein. This work provides novel insights into the
role of the Sinorhizobium meliloti PhoU protein, which plays a key role in rapid
adaptation to elevated phosphate concentrations. It is shown that PhoU rapidly
responds to elevated phosphate levels by significantly decreasing the phosphate
transport of PstSCAB, thereby preventing phosphate toxicity and cell death.
Additionally, a new model for phosphate sensing in bacterial species which
involves the PhoR-PhoB two-component system is presented. This work provides new
insights into the bacterial response to changing environmental conditions and
into regulation of the phosphate limitation response that influences numerous
bacterial processes, including antibiotic production and virulence.
PMID- 28416710
TI - Compliance with Uruguay's single presentation requirement.
AB - INTRODUCTION: Tobacco companies vary pack colours, designs, descriptors, flavours
and brand names on cigarette packs to target a multitude of consumers. These
different brand variants can falsely imply that some brand variants are less
harmful than others. Uruguay is the only country that requires cigarette
companies to adhere to a single presentation (one brand variant) per brand
family. METHODS: An existing, systematic pack purchasing protocol was adapted for
data collection. Neighbourhoods in Montevideo were categorised into five strata
by percentage of poor households. Five neighbourhoods within each stratum were
selected based on geographical variation. In each neighbourhood, a 'starting hub'
was identified and a systematic walking protocol was implemented to purchase
unique packs at four key vendor types. RESULTS: Unique packs were purchased in 9
out of 25 neighbourhoods. Fifty-six unique packs were purchased, representing 30
brands. Of these, 51 packs were legal, representing 26 brands. The majority of
the legal brands (n=16; 62%) were compliant with the requirement. The remaining
packs were non-compliant due to differences in colour, design element, brand
name, crest and descriptors. Although not prohibited by the single presentation
requirement, 16 legal brands had more than one stick count (10, 11, 14 or 20
sticks), and packs from four brands had more than one packaging type (hard, soft
or tin). CONCLUSION: Overall, compliance with Uruguay's single presentation
requirement was good. In addition to the current restrictions, future single
presentation requirements could expand to include packs in more than one stick
count and packaging type.
PMID- 28416712
TI - Comment on "A Database of Human Immune Receptor Alleles Recovered from Population
Sequencing Data".
PMID- 28416713
TI - Response to Comment on "A Database of Human Immune Receptor Alleles Recovered
from Population Sequencing Data".
PMID- 28416709
TI - Spheres of Hope, Packets of Doom: the Good and Bad of Outer Membrane Vesicles in
Interspecies and Ecological Dynamics.
AB - Outer membrane vesicles (OMVs) are proteoliposome nanoparticles ubiquitously
produced by Gram-negative bacteria. Typically bearing a composition similar to
those of the outer membrane and periplasm of the cells from which they are
derived, OMVs package an array of proteins, lipids, and nucleic acids. Once
considered inconsequential by-products of bacterial growth, OMVs have since been
demonstrated to mediate cellular stress relief, promote horizontal gene transfer
and antimicrobial activity, and elicit metazoan inflammation. Recently, OMVs have
gained appreciation as critical moderators of interorganismal dynamics. In this
review, we focus on recent progress toward understanding the functions of OMVs
with regard to symbiosis and ecological contexts, and we propose potential
avenues for future OMV studies.
PMID- 28416714
TI - JingleBells: A Repository of Immune-Related Single-Cell RNA-Sequencing Datasets.
AB - Recent advances in single-cell RNA-sequencing (scRNA-seq) technology increase the
understanding of immune differentiation and activation processes, as well as the
heterogeneity of immune cell types. Although the number of available immune
related scRNA-seq datasets increases rapidly, their large size and various
formats render them hard for the wider immunology community to use, and read
level data are practically inaccessible to the non-computational immunologist. To
facilitate datasets reuse, we created the JingleBells repository for immune
related scRNA-seq datasets ready for analysis and visualization of reads at the
single-cell level (http://jinglebells.bgu.ac.il/). To this end, we collected the
raw data of publicly available immune-related scRNA-seq datasets, aligned the
reads to the relevant genome, and saved aligned reads in a uniform format,
annotated for cell of origin. We also added scripts and a step-by-step tutorial
for visualizing each dataset at the single-cell level, through the commonly used
Integrated Genome Viewer (www.broadinstitute.org/igv/). The uniform scRNA-seq
format used in JingleBells can facilitate reuse of scRNA-seq data by
computational biologists. It also enables immunologists who are interested in a
specific gene to visualize the reads aligned to this gene to estimate cell
specific preferences for splicing, mutation load, or alleles. Thus JingleBells is
a resource that will extend the usefulness of scRNA-seq datasets outside the
programming aficionado realm.
PMID- 28416715
TI - T Cell-Transfer Experimental Autoimmune Encephalomyelitis: Pillar of Multiple
Sclerosis and Autoimmunity.
PMID- 28416716
TI - Pillars Article: The Rapid Isolation of Clonable Antigen-specific T Lymphocyte
Lines Capable of Mediating Autoimmune Encephalomyelitis. Eur J Immunol. 1981.11:
195-199.
PMID- 28416718
TI - Correction: Disruption of Nrf2 Impairs the Resolution of Hyperoxia-Induced Acute
Lung Injury and Inflammation in Mice.
PMID- 28416717
TI - Essential Neuroscience in Immunology.
AB - The field of immunology is principally focused on the molecular mechanisms by
which hematopoietic cells initiate and maintain innate and adaptive immunity.
That cornerstone of attention has been expanded by recent discoveries that
neuronal signals occupy a critical regulatory niche in immunity. The discovery is
that neuronal circuits operating reflexively regulate innate and adaptive
immunity. One particularly well-characterized circuit regulating innate immunity,
the inflammatory reflex, is dependent upon action potentials transmitted to the
reticuloendothelial system via the vagus and splenic nerves. This field has grown
significantly with the identification of several other reflexes regulating
discrete immune functions. As outlined in this review, the delineation of these
mechanisms revealed a new understanding of immunity, enabled a first-in-class
clinical trial using bioelectronic devices to inhibit cytokines and inflammation
in rheumatoid arthritis patients, and provided a mosaic view of immunity as the
integration of hematopoietic and neural responses to infection and injury.
PMID- 28416719
TI - Correction: Cutting Edge: Integrin alpha4 Is Required for Regulatory B Cell
Control of Experimental Autoimmune Encephalomyelitis.
PMID- 28416721
TI - Correction: A Database of Human Immune Receptor Alleles Recovered from Population
Sequencing Data.
PMID- 28416722
TI - Correction: Prevention of Vgamma9Vdelta2 T Cell Activation by a Vgamma9Vdelta2
TCR Nanobody.
PMID- 28416720
TI - Correction: Key Residues at Third CDR3beta Position Impact Structure and Antigen
Recognition of Human Invariant NK TCRs.
PMID- 28416723
TI - The origin of inner Solar System water.
AB - Of the potential volatile sources for the terrestrial planets, the CI and CM
carbonaceous chondrites are closest to the planets' bulk H and N isotopic
compositions. For the Earth, the addition of approximately 2-4 wt% of CI/CM
material to a volatile-depleted proto-Earth can explain the abundances of many of
the most volatile elements, although some solar-like material is also required.
Two dynamical models of terrestrial planet formation predict that the
carbonaceous chondrites formed either in the asteroid belt ('classical' model) or
in the outer Solar System (5-15 AU in the Grand Tack model). To test these
models, at present the H isotopes of water are the most promising indicators of
formation location because they should have become increasingly D-rich with
distance from the Sun. The estimated initial H isotopic compositions of water
accreted by the CI, CM, CR and Tagish Lake carbonaceous chondrites were much more
D-poor than measured outer Solar System objects. A similar pattern is seen for N
isotopes. The D-poor compositions reflect incomplete re-equilibration with H2 in
the inner Solar System, which is also consistent with the O isotopes of
chondritic water. On balance, it seems that the carbonaceous chondrites and their
water did not form very far out in the disc, almost certainly not beyond the
orbit of Saturn when its moons formed (approx. 3-7 AU in the Grand Tack model)
and possibly close to where they are found today.This article is part of the
themed issue 'The origin, history and role of water in the evolution of the inner
Solar System'.
PMID- 28416724
TI - On the attempts to measure water (and other volatiles) directly at the surface of
a comet.
AB - The Ptolemy instrument on the Philae lander (of the Rosetta space mission) was
able to make measurements of the major volatiles, water, carbon monoxide and
carbon dioxide, directly at the surface of comet 67P/Churyumov-Gerasimenko. We
give some background to the mission and highlight those instruments that have
already given insights into the notion of water in comets, and which will
continue to do so as more results are either acquired or more fully interpreted.
On the basis of our results, we show how comets may in fact be heterogeneous over
their surface, and how surface measurements can be used in a quest to comprehend
the daily cycles of processes that affect the evolution of comets.This article is
part of the themed issue 'The origin, history and role of water in the evolution
of the inner Solar System'.
PMID- 28416725
TI - The search for and analysis of direct samples of early Solar System aqueous
fluids.
AB - We describe the current state of the search for direct, surviving samples of
early, inner Solar System fluids-fluid inclusions in meteorites. Meteoritic
aqueous fluid inclusions are not rare, but they are very tiny and their
characterization is at the state of the art for most analytical techniques.
Meteoritic fluid inclusions offer us a unique opportunity to study early Solar
System brines in the laboratory. Inclusion-by-inclusion analyses of the trapped
fluids in carefully selected samples will, in the immediate future, provide us
detailed information on the evolution of fluids as they interacted with anhydrous
solid materials. Thus, real data can replace calculated fluid compositions in
thermochemical calculations of the evolution of water and aqueous reactions in
comets, asteroids, moons and the terrestrial planets.This article is part of the
themed issue 'The origin, history and role of water in the evolution of the inner
Solar System'.
PMID- 28416726
TI - D/H ratios of the inner Solar System.
AB - The original hydrogen isotope (D/H) ratios of different planetary bodies may
indicate where each body formed in the Solar System. However, geological and
atmospheric processes can alter these ratios through time. Over the past few
decades, D/H ratios in meteorites from Vesta and Mars, as well as from S- and C
type asteroids, have been measured. The aim of this article is to bring together
all previously published data from these bodies, as well as the Earth, in order
to determine the original D/H ratio for each of these inner Solar System
planetary bodies. Once all secondary processes have been stripped away, the inner
Solar System appears to be relatively homogeneous in terms of water D/H, with the
original water D/H ratios of Vesta, Mars, the Earth, and S- and C-type asteroids
all falling between deltaD values of -1000/00 and -5900/00. This homogeneity is
in accord with the 'Grand tack' model of Solar System formation, where giant
planet migration causes the S- and C-type asteroids to be mixed within 1 AU to
eventually form the terrestrial planets.This article is part of the themed issue
'The origin, history and role of water in the evolution of the inner Solar
System'.
PMID- 28416727
TI - Remotely distinguishing and mapping endogenic water on the Moon.
AB - Water and/or hydroxyl detected remotely on the lunar surface originates from
several sources: (i) comets and other exogenous debris; (ii) solar-wind
implantation; (iii) the lunar interior. While each of these sources is
interesting in its own right, distinguishing among them is critical for testing
hypotheses for the origin and evolution of the Moon and our Solar System.
Existing spacecraft observations are not of high enough spectral resolution to
uniquely characterize the bonding energies of the hydroxyl molecules that have
been detected. Nevertheless, the spatial distribution and associations of H, OH-
or H2O with specific lunar lithologies provide some insight into the origin of
lunar hydrous materials. The global distribution of OH-/H2O as detected using
infrared spectroscopic measurements from orbit is here examined, with particular
focus on regional geological features that exhibit OH-/H2O absorption band
strengths that differ from their immediate surroundings.This article is part of
the themed issue 'The origin, history and role of water in the evolution of the
inner Solar System'.
PMID- 28416728
TI - Global water cycle and the coevolution of the Earth's interior and surface
environment.
AB - The bulk Earth composition contains probably less than 0.3% of water, but this
trace amount of water can affect the long-term evolution of the Earth in a number
of different ways. The foremost issue is the occurrence of plate tectonics, which
governs almost all aspects of the Earth system, and the presence of water could
either promote or hinder the operation of plate tectonics, depending on where
water resides. The global water cycle, which circulates surface water into the
deep mantle and back to the surface again, could thus have played a critical role
in the Earth's history. In this contribution, we first review the present-day
water cycle and discuss its uncertainty as well as its secular variation. If the
continental freeboard has been roughly constant since the Early Proterozoic,
model results suggest long-term net water influx from the surface to the mantle,
which is estimated to be 3-4.5*1014 g yr-1 on the billion years time scale. We
survey geological and geochemical observations relevant to the emergence of
continents above the sea level as well as the nature of Precambrian plate
tectonics. The global water cycle is suggested to have been dominated by
regassing, and its implications for geochemical cycles and atmospheric evolution
are also discussed.This article is part of the themed issue 'The origin, history
and role of water in the evolution of the inner Solar System'.
PMID- 28416729
TI - The fate of water within Earth and super-Earths and implications for plate
tectonics.
AB - The Earth is likely to have acquired most of its water during accretion. Internal
heat of planetesimals by short-lived radioisotopes would have caused some water
loss, but impacts into planetesimals were insufficiently energetic to produce
further drying. Water is thought to be critical for the development of plate
tectonics, because it lowers viscosities in the asthenosphere, enabling
subduction. The following issue persists: if water is necessary for plate
tectonics, but subduction itself hydrates the upper mantle, how is the upper
mantle initially hydrated? The giant impacts of late accretion created magma
lakes and oceans, which degassed during solidification to produce a heavy
atmosphere. However, some water would have remained in the mantle, trapped within
crystallographic defects in nominally anhydrous minerals. In this paper, we
present models demonstrating that processes associated with magma ocean
solidification and overturn may segregate sufficient quantities of water within
the upper mantle to induce partial melting and produce a damp asthenosphere,
thereby facilitating plate tectonics and, in turn, the habitability of Earth-like
extrasolar planets.This article is part of the themed issue 'The origin, history
and role of water in the evolution of the inner Solar System'.
PMID- 28416730
TI - Early accretion of water and volatile elements to the inner Solar System:
evidence from angrites.
AB - Inner Solar System bodies are depleted in volatile elements relative to chondrite
meteorites, yet the source(s) and mechanism(s) of volatile-element depletion
and/or enrichment are poorly constrained. The timing, mechanisms and quantities
of volatile elements present in the early inner Solar System have vast
implications for diverse processes, from planetary differentiation to the
emergence of life. We report major, trace and volatile-element contents of a
glass bead derived from the D'Orbigny angrite, the hydrogen isotopic composition
of this glass bead and that of coexisting olivine and silicophosphates, and the
207Pb-206Pb age of the silicophosphates, 4568 +/- 20 Ma. We use volatile
saturation models to demonstrate that the angrite parent body must have been a
major body in the early inner Solar System. We further show via mixing
calculations that all inner Solar System bodies accreted volatile elements with
carbonaceous chondrite H and N isotope signatures extremely early in Solar System
history. Only a small portion (if any) of comets and gaseous nebular H species
contributed to the volatile content of the inner Solar System bodies.This article
is part of the themed issue 'The origin, history and role of water in the
evolution of the inner Solar System'.
PMID- 28416731
TI - The origin, history and role of water in the evolution of the inner Solar System.
PMID- 28416732
TI - Prevalence of kidney stones and associated risk factors in the Shunyi District of
Beijing, China.
AB - INTRODUCTION: Kidney stone formation is a multifactorial condition that involves
interaction of environmental and genetic factors. Presence of kidney stones is
strongly related to other diseases, which may result in a heavy economic and
social burden. Clinical data on the prevalence and influencing factors in kidney
stone disease in the north of China are scarce. In this study, we explored the
prevalence of kidney stone and potentially associated risk factors in the Shunyi
District of Beijing, China. METHODS: A population-based cross-sectional study was
conducted from December 2011 to November 2012 in a northern area of China.
Participants were interviewed in randomly selected towns. Univariate analysis of
continuous and categorical variables was first performed by calculation of
Spearman's correlation coefficient and Pearson Chi squared value, respectively.
Variables with statistical significance were further analysed by multivariate
logistic regression to explore the potential influencing factors. RESULTS: A
total of 3350 participants (1091 males and 2259 females) completed the survey and
the response rate was 99.67%. Among the participants, 3.61% were diagnosed with
kidney stone. Univariate analysis showed that significant differences were
evident in 31 variables. Blood and urine tests were performed in 100 randomly
selected patients with kidney stone and 100 healthy controls. Serum creatinine,
calcium, and uric acid were significantly different between the patients with
kidney stone and healthy controls. Multivariate logistic regression revealed that
being male (odds ratio=102.681; 95% confidence interval, 1.062-9925.797), daily
intake of white spirits (6.331; 1.204-33.282), and a history of urolithiasis
(1797.775; 24.228-133 396.982) were factors potentially associated with kidney
stone prevalence. CONCLUSIONS: Male gender, drinking white spirits, and a history
of urolithiasis are potentially associated with kidney stone formation.
PMID- 28416733
TI - Factors associated with multidisciplinary case conference outcomes in children
admitted to a regional hospital in Hong Kong with suspected child abuse: a
retrospective case series with internal comparison.
AB - INTRODUCTION: In all cases of suspected child abuse, accurate risk assessment is
vital to guide further management. This study examined the relationship between
risk factors in a risk assessment matrix and child abuse case conference
outcomes. METHODS: Records of all children hospitalised at United Christian
Hospital in Hong Kong for suspected child abuse from January 2012 to December
2014 were reviewed. Outcomes of the hospital abuse work-up as concluded in the
Multi-Disciplinary Case Conference were categorised as 'established', 'high
risk', or 'not established'. All cases of 'established' and 'high risk' were
included in the positive case conference outcome group and all cases of 'not
established' formed the comparison group. On the other hand, using the Risk
Assessment Matrix developed by the California State University, Fresno in 1990,
each case was allotted a matrix score of low, intermediate, or high risk in each
of 15 matrix domains, and an aggregate matrix score was derived. The effect of
individual matrix domain on case conference outcome was analysed. Receiver
operating characteristic curve analysis was used to examine the relationship
between case conference outcome and aggregate matrix score. RESULTS: In this
study, 265 children suspected of being abused were included, with 198 in the
positive case conference outcome group and 67 in the comparison group. Three
matrix domains (severity and frequency of abuse, location of injuries, and
strength of family support systems) were significantly associated with case
conference outcome. An aggregate cut-off score of 23 yielded a sensitivity of
91.4% and specificity of 38.2% in relation to outcome of abuse categorisation.
CONCLUSIONS: Risk assessment should be performed when handling suspected child
abuse cases. A high aggregate score should arouse suspicion in all disciplines
managing child abuse cases.
PMID- 28416734
TI - The angiotensin receptor blocker, Losartan, inhibits mammary tumor development
and progression to invasive carcinoma.
AB - Drugs that target the Renin-Angiotensin System (RAS) have recently come into
focus for their potential utility as cancer treatments. The use of Angiotensin
Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors
(ACEIs) to manage hypertension in cancer patients is correlated with improved
survival outcomes for renal, prostate, breast and small cell lung cancer.
Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is
linked to breast cancer pathogenesis, with unbiased analysis of gene-expression
studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in
ER+ve/HER2-ve tumors correlating with poor prognosis. However, there is no
evidence, so far, of the functional contribution of AT1R to breast tumorigenesis.
We explored the potential therapeutic benefit of ARB in a carcinogen-induced
mouse model of breast cancer and clarified the mechanisms associated with its
success.Mammary tumors were induced with 7,12-dimethylbenz[alpha]antracene (DMBA)
and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of
the ARB, Losartan treatment assessed in a preventative setting (n = 15 per
group). Tumor histopathology was characterised by immunohistochemistry, real-time
qPCR to detect gene expression signatures, and tumor cytokine levels measured
with quantitative bioplex assays. AT1R was detected with radiolabelled ligand
binding assays in fresh frozen tumor samples.We showed that therapeutic
inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor
burden; and no mammary tumor incidence in 20% of animals. We observed a
significant reduction in tumor progression from DCIS to invasive cancer with
Losartan treatment. This was associated with reduced tumor cell proliferation and
a significant reduction in IL-6, pSTAT3 and TNFalpha levels. Analysis of tumor
immune cell infiltrates, however, demonstrated no significant differences in the
recruitment of lymphocytes or tumour-associated macrophages in Losartan or
vehicle-treated mammary tumors.Analysis of AT1R expression with radiolabelled
ligand binding assays in human breast cancer biopsies showed high AT1R levels in
30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA
database identified that high AT1R expression to be associated with luminal
breast cancer subtype.Our in vivo data and analysis of human invasive ductal
carcinoma samples identify the AT1R is a potential therapeutic target in breast
cancer, with the availability of a range of well-tolerated inhibitors currently
used in clinics. We describe a novel signalling pathway critical in breast
tumorigenesis, that may provide new therapeutic avenues to complement current
treatments.
PMID- 28416735
TI - Reciprocal control of lncRNA-BCAT1 and beta-catenin pathway reveals lncRNA-BCAT1
long non-coding RNA acts as a tumor suppressor in colorectal cancer.
AB - beta-catenin plays a major role in tumor development and progression. The present
study found that beta-catenin was upregulated in 30 samples of colorectal cancer
(CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non
coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets,
which were generated via the Affymetrix plus 2.0 microarray platform and
downloaded from the GEO database, revealed 20 differentially expressed lncRNAs
following beta-catenin knockdown. We focused on AK091631, a novel lncRNA, which
we named lncRNA-beta-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1
expression was decreased in CRC tissues, and was negatively associated with beta
catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression
suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and
MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell
growth and invasion via Wnt/beta-catenin pathway blockade, and that lncRNA-BCAT1
is repressed by Wnt/beta-catenin signaling. This evidence suggests that lncRNA
BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic
biomarker in CRC.
PMID- 28416736
TI - NOMO-1 gene is deleted in early-onset colorectal cancer.
AB - To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in
Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess
the status of NOMO1, a gene located in that region, we analyzed differential
clinicopathological, familial and molecular features of CRC subsets with and
without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We
confirmed the region by fluorescence in-situ hybridization, and Quantitative Real
Time PCR analyzed the status of NOMO1 in different age-of-onset and
Microsatellite Instability (MSI)-status CRC subsets. Both age-of-onset subsets
were subsequently extended to further confirm NOMO1 gene changes. 16p13.12-p13.11
alterations were observed in 23.3% of CRCs, and was detected more frequently in
EOCRC (33.3%) than in late-onset CRC (16.3%). The group with deletion in 16p
showed a higher frequency of females and left-colon locations; a better
prognosis; and higher Chromosomal Instability. Within the primary EOCRC
population, 34 out of 34 of tumours showed a homozygous deletion in NOMO1, while
in the late-onset population only 2 of the 17 tumours (11.7%) showed it. In the
extended group, we found 61 out of 75 EOCRC patients (81.3%) with homozygous
deletion and 7 patients (9.3%) with heterozygous deletion of NOMO1; moreover, in
the new 50 late-onset patients, the proportions of deletions decreased.
Microsatellite-Stable (MSS) EOCRC showed a very high proportion of homozygous
loss of NOMO1 (54 of 59 cases, 91.5%), while the deletion was observed in only 7
out of 16 MSI cases. Deletion of NOMO1 is a molecular marker predominantly
associated with EOCRC, particularly MSS subtypes.
PMID- 28416737
TI - Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired
resistance in human lung cancer cells with activating mutation of EGFR.
AB - PURPOSE: The aim of this work was to investigate the efficacy of sequential
treatment with first-, second- and third-generation epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired
resistance occurring during the sequential use of these inhibitors. EXPERIMENTAL
DESIGN: We developed an in vivo model of acquired resistance to EGFR-inhibitors
by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer
(NSCLC) cell line harboring EGFR activating mutation, with a sequence of first
generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib),
of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal
antibody cetuximab, and of third-generation EGFR-TKI (osimertinib). RESULTS:
HCC827-derived xenografts and with acquired resistance to EGFR-inhibitors were
sensitive to the sequential use of first-, second- and third-generation EGFR
TKIs. Continuous EGFR inhibition of first-generation resistant tumors by
sequential treatment with afatinib plus/minus cetuximab, followed by osimertinib,
represented an effective therapeutic strategy in this model. Whereas T790M
resistance mutation was not detected, a major mechanism of acquired resistance
was the activation of components of the Hedgehog (Hh) pathway. This phenomenon
was accompanied by epithelial-to-mesenchymal transition. Cell lines established
in vitro from gefitinib-, or afatinib- or osimertinib-resistant tumors showed
metastatic properties and maintained EGFR-TKIs resistance in vitro, that was
reverted by the combined blockade of Hh, with the selective SMO inhibitor
sonidegib, and EGFR. CONCLUSIONS: EGFR-mutant NSCLC can benefit from continuous
treatment with EGFR-inhibitors, indepenently from mechanisms of resistance. In a
complex and heterogenous scenario, Hh showed an important role in mediating
resistance to EGFR-inhibitors through the induction of mesenchymal properties.
PMID- 28416738
TI - Differential expression of folate receptor 1 in medulloblastoma and the
correlation with clinicopathological characters and target therapeutic potential.
AB - Medulloblastoma is the most common malignant brain tumor in children. Folate
receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies.
However the expression profile and the role of clinicopathological significance
and therapeutic target potential in medulloblastoma still remain elusive.
Currently we detected the expression of Folr1 in medulloblastoma and identified
the diagnostic application by evaluating the clinical, pathological and
neuroimaging values. Then we developed a target therapeutic compound with Folr1,
which exhibited promising efficiency in treatment of medulloblastoma. Folr1
expression was up-regulated in medulloblastoma and positively correlated with
percentage of Ki-67 and MMP9 labeling, pathological subtypes, serum Folr1 levels
and CSF spreading on MRI. The level of serum Folr1 showed rational sensitivity
and specificity in predicting histological subgroups. Strong Folr1 expression was
recommended as the independent value regarding the prognosis of patients with
medulloblastoma. Folr1 targeted therapy attenuated the tumor growth and
metastasis with down-regulation of MMPs proteins and activation of apoptosis.
Immunostaining analysis in the xenograft samples showed the decreased Ki-67 and
MMP9 index providing the strong evidences that Folr1 targeted application can
suppress the proliferation and invasion. Our findings uncovered in Folr1 a
predictive candidate and therapeutic target for medulloblastoma.
PMID- 28416739
TI - TKI rotation-induced persistent deep molecular response in multi-resistant blast
crisis of Ph+ CML.
AB - In chronic myeloid leukemia (CML) resistance against one or more BCR-ABL1
tyrosine kinase inhibitors (TKI) remains a clinical challenge. Preclinical data
suggest that TKI combinations may overcome resistance. We report on a heavily pre
treated 78 year-old female patient with CML who developed multi-resistant blast
crisis with bone marrow fibrosis and a Ph- clone. Treatment with ponatinib
resulted in blast cell clearance, decrease in fibrosis, and disappearance of BCR
ABL1, but also in severe thrombocytopenia with bleedings requiring platelet
transfusions. We therefore switched from ponatinib to bosutinib. During
bosutinib, platelet counts recovered. However, after 6 months, BCR-ABL1 mRNA
levels increased to > 1%. Therefore, we 'switched back' to ponatinib, and this
was again followed by disappearance of BCR-ABL1 and a decrease in platelets.
During the next 2 years, we applied ponatinib and bosutinib in continuous
rotation-cycles and added hydroxyurea in order to suppress all sub-clones and to
balance between efficacy and potential side effects following the principle of
personalized medicine. With this approach the patient remained in complete
molecular response and reached normal blood counts and a normal quality of life
without vascular or other side effects. In conclusion, TKI rotation is a novel
potent approach to suppress multiple resistant sub-clones and to balance between
clinical efficacy and side effects in patients with advanced CML. Clinical trials
are now warranted to show that TKI-rotation is in general safe and effective in
these patients.
PMID- 28416740
TI - Multi-targeting therapeutic mechanisms of the Chinese herbal medicine QHD in the
treatment of non-alcoholic fatty liver disease.
AB - Beneficial effects of the Chinese herbal medicine Qushi Huayu Decoction (QHD)
were observed with non-alcoholic fatty liver disease (NAFLD) patients and animal
models. The impact of QHD or its active components (geniposide and chlorogenic
acid, GC) on NAFLD liver transcriptome and gut microbiota was examined with NAFLD
rats. Increased expression for genes required for glutathione production and
decreased expression for genes required for lipid synthesis was observed in NAFLD
livers treated with QHD and GC. GC treatment decreased serum LPS, which could be
explained by reduced mucosal damage in the colon of GC-treated rats. Further, our
data suggest an increased abundance of Treg-inducing bacteria that stimulated the
Treg activity in GC treated colon, which in turn down-regulated inflammatory
signals, improved gut barrier function and consequently reduced hepatic exposure
to microbial products. Our study suggests that QHD simultaneously enhanced the
hepatic anti-oxidative mechanism, decreased hepatic lipid synthesis, and promoted
the regulatory T cell inducing microbiota in the gut.
PMID- 28416741
TI - Relaxin abrogates renal interstitial fibrosis by regulating macrophage
polarization via inhibition of Toll-like receptor 4 signaling.
AB - Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit
the CKD process, it is important to prevent renal fibrosis, though CKD remains
incurable. Renal fibrosis can be inhibited by relaxin in several experimental
models, but the mechanism of relaxin for antifibrotic potential is still not
clear. And here we have studied the role of relaxin in macrophage polarization
and renal inflammation after unilateral ureteral obstruction (UUO). Our results
show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling,
shift macrophage polarization toward the M2 phenotype and ameliorat renal
fibrosis in the early stages of UUO. In vitro experiments, it has been confirmed
that relaxin can downregulate the TLR4 signaling and induce the M2 macrophage
transition. Furthermore, the transitional actions of macrophage phenotype induced
by relaxin are significantly blocked by TAK-242, a TLR4 antagonist, in vitro
experiments. Thus, there is a novel mechanism of relaxin for antifibrosis that
shifts macrophage polarization toward the M2 phenotype via inhibition of TLR4
signaling.
PMID- 28416742
TI - Model driven optimization of antiangiogenics + cytotoxics combination:
application to breast cancer mice treated with bevacizumab + paclitaxel doublet
leads to reduced tumor growth and fewer metastasis.
AB - Bevacizumab is the first-in-class antiangiogenic drug and is almost always
administrated in combination with cytotoxics. Reports have shown that bevacizumab
could induce a transient phase of vascular normalization, thus ensuring a better
drug delivery when cytotoxics administration is adjuvant. However, determining
the best sequence remains challenging. We have developed a mathematical model
describing the impact of antiangiogenics on tumor vasculature. A 3.4 days gap
between bevacizumab and paclitaxel was first proposed by our model. To test its
relevance, 84 mice were orthotopically xenografted with human MDA-231Luc+
refractory breast cancer cells. Two sets of experiments were performed, based
upon different bevacizumab dosing (10 or 20 mg/kg) and inter-cycle intervals (7
or 10 days), comprising several combinations with paclitaxel. Results showed that
scheduling bevacizumab 3 days before paclitaxel improved antitumor efficacy (48%
reduction in tumor size compared with concomitant dosing, p < 0.05) and reduced
metastatic spreading. Additionally, bevacizumab alone could lead to more
aggressive metastatic disease with shorter survival in animals. Our model was
able to fit the experimental data and provided insights on the underlying
dynamics of the vasculature's ability to deliver the cytotoxic agent. Final
simulations suggested a new, data-informed optimal gap of 2.2 days. Our
experimental data suggest that current concomitant dosing between bevacizumab and
paclitaxel could be a sub-optimal strategy at bedside. In addition, this proof of
concept study suggests that mathematical modelling could help to identify the
optimal interval among a variety of possible alternate treatment modalities, thus
refining the way experimental or clinical studies are conducted.
PMID- 28416743
TI - The urokinase plasminogen activation system in gastroesophageal cancer: A
systematic review and meta-analysis.
AB - BACKGROUND: The urokinase plasminogen activation (uPA) system is a crucial
pathway for tumour invasion and establishment of metastasis. Although there is
good evidence that uPA system expression is a clinically relevant biomarker in
some solid tumours, its role in gastroesophageal cancer is uncertain. RESULTS: We
identified 22 studies encompassing 1966 patients which fulfilled the inclusion
criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high
risk clinicopathological features. High uPA expression is associated with a
shorter RFS (HR 1.90 95% 1.16-3.11, p = 0.01) and OS (HR 2.21 95% CI 1.74-2.80, p
< 0.0001). High uPAR expression is associated with poorer OS (HR 2.21 95%CI 1.82
2.69, p < 0.0001). High PAI-1 expression is associated with shorter RFS (HR 1.96
96% CI 1.07-3.58, p = 0.03) and OS (HR 1.84 95%CI 1.28-2.64, p < 0.0001). There
was no significant association between PAI-2 expression and OS (HR 0.97 95%CI
0.48-1.94, p < 0.92) although data was limited. MATERIALS AND METHODS: We
undertook a systematic review evaluating expression of uPA, urokinase plasminogen
activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1/SerpinE1) and
plasminogen activator inhibitor-2 (PAI-2/SerpinB2) on primary oesophageal, gastro
oesophageal junction, and gastric adenocarcinomas. We performed a meta-analysis
of clinicopathological associations, overall survival (OS) and recurrence free
survival (RFS). CONCLUSIONS: We conclude that the uPA system is a clinically
relevant biomarker in primary gastroesophageal cancer, with higher expression of
uPA, uPAR and PAI-1 associated with higher risk disease and poorer prognosis.
This also highlights the potential utility of the uPA system as a therapeutic
target for improved treatment strategies.
PMID- 28416744
TI - Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for
intraoperative visualization of multiple cancer types.
AB - Incomplete resections and damage to critical structures increase morbidity and
mortality of patients with cancer. Targeted intraoperative fluorescence imaging
aids surgeons by providing real-time visualization of tumors and vital
structures. This study evaluated the tumor-targeted zwitterionic near-infrared
fluorescent peptide cRGD-ZW800-1 as tracer for intraoperative imaging of multiple
cancer types. cRGD-ZW800-1 was validated in vitro on glioblastoma (U-87 MG) and
colorectal (HT-29) cell lines. Subsequently, the tracer was tested in orthotopic
mouse models with HT-29, breast (MCF-7), pancreatic (BxPC-3), and oral (OSC-19)
tumors. Dose-ranging studies, including doses of 0.25, 1.0, 10, and 30 nmol, in
xenograft tumor models suggest an optimal dose of 10 nmol, corresponding to a
human equivalent dose of 63 MUg/kg, and an optimal imaging window between 2 and
24 h post-injection. The mean half-life of cRGD-ZW800-1 in blood was 25 min.
Biodistribution at 4 h showed the highest fluorescence signals in tumors and
kidneys. In vitro and in vivo competition experiments showed significantly lower
fluorescence signals when U-87 MG cells (minus 36%, p = 0.02) or HT-29 tumor
bearing mice (TBR at 4 h 3.2 +/- 0.5 vs 1.8 +/- 0.4, p = 0.03) were
simultaneously treated with unlabeled cRGD. cRGD-ZW800-1 visualized in vivo all
colorectal, breast, pancreatic, and oral tumor xenografts in mice. Screening for
off-target interactions, cRGD-ZW800-1 showed only inhibition of COX-2, likely due
to binding of cRGD-ZW800-1 to integrin alphaVbeta3. Due to its recognition of
various integrins, which are expressed on malignant and neoangiogenic cells, it
is expected that cRGD-ZW800-1 will provide a sensitive and generic tool to
visualize cancer during surgery.
PMID- 28416745
TI - Stable H3 peptide was delivered by gold nanorods to inhibit LSD1 activation and
induce human mesenchymal stem cells differentiation.
AB - Recently, lysine-specific demethylase 1 (LSD1), which is the first identified
histone demethylase, regulates post-translational modifications and has great
promise as new targets for cancer and other diseases. Moreover, the ability of
LSD1 to induce the differentiation of stem cells has attracted great attention in
biological fields. In this study, we designed LSD1 peptide inhibitor based on its
substrate H3 peptide. Through introducing a disulfide bond to stabilize the
native peptide into alpha helical structure, we get a peptide with higher cell
permeability and stability compared to its parent form. Using gold nanorods
(AuNRs) as delivery systems to deliver stable peptide into human MSCs, the
delivery efficiency has been enhanced significantly by flow cytometry and cell
fluorescent imaging. The intracellular delivery of stable peptide by AuNRs-PEI
based nanocarriers could inhibit the activation of LSD1, which together with
hepatocyte growth factor (HGF) exhibits obviously synergistic effect to induce
human MSCs differentiation. Furthermore, the hepatic marker genes AFP (alpha
fetal protein) and ck19 are up-regulated by AuNRs-stable peptide (AuNRs- SP- PEI)
with HGF. In conclusion, our study is the first time to use stable H3 peptide to
inhibit LSD1 activation, which has been further delivered by AuNRs as
nanocarriers into human MSCs.
PMID- 28416747
TI - The TERT promoter mutation incidence is modified by germline TERT rs2736098 and
rs2736100 polymorphisms in hepatocellular carcinoma.
AB - Telomerase activation via induction of the catalytic component telomerase reverse
transcriptase (TERT) plays essential roles in malignant transformation. TERT
promoter-activating mutations were recently identified as a novel mechanism to
activate telomerase in hepatocellular carcinoma (HCC) and many other
malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT
rs2736098 and rs2736100 are significantly associated with cancer susceptibility.
It is currently unclear whether different germline TERT variants modify TERT
promoter mutations. Here we analyzed the TERT promoter status and genotyped the
TERT SNPs at rs2736098 and rs2736100 in patients with HCC. Thirty percent of HCCs
harbored TERT promoter mutations and there was a significant difference in
rs2736098 and rs2736100 genotypes between wt and mutant TERT promoter-bearing HCC
tumors (P = 0.007 and 0.018, respectively). For rs2736100, the cancer risk
genotype CC was significantly associated with a reduced incidence of TERT
promoter mutations compared to AA + AC variants [Odds ratio (OR): 0.181, 95%
Confidence interval (CI): 0.0543-0.601, P = 0.004]. The rs2736098_CT genotype was
significantly associated with the TERT promoter mutation-positive tumors compared
to the TT genotype (OR: 5.391, 95% CI: 1.234-23.553, P = 0.025). These
differences in genotype distribution did not differ between patients with a wt
TERT promoter and controls. The presence of TERT promoter mutations was not
associated with clinico-pathological variables. Taken together, the germline TERT
genetic background may significantly affect the onset of TERT promoter mutations
in HCCs, which provides a better understanding of HCC-related TERT promoter
mutations and telomerase regulation in cancer.
PMID- 28416748
TI - Differential expression of M3 muscarinic receptors in progressive colon neoplasia
and metastasis.
AB - M3 muscarinic receptor (M3R) activation promotes colon cancer cell proliferation,
migration, and invasion in vitro. Although over-expression of CHRM3, the gene
encoding M3R, is reported in primary colon cancers, expression of M3R itself has
not been studied in colon neoplasia. We compared M3R expression in normal colon
to colon adenomas, and primary and metastatic colon cancers. Compared to adjacent
normal colon, CHRM3 expression was increased up to 128-fold in 10 of 18
consecutive surgical cancer specimens (56%) and associated with metastatic spread
(P < 0.05). To analyze M3R protein expression we interrogated 29 consecutive
paraffin-embedded colon adenocarcinomas and adjacent normal colon using a
specific anti-M3R antibody and immunoperoxidase staining. This revealed weak M3R
expression in normal colonocytes, primarily on basolateral surfaces. In contrast,
in 25 of 29 cancer tissues (86%) we observed both cytoplasmic and plasma membrane
over-expression of M3R; compared to normal epithelium, mean M3R staining
intensity was increased more than two-fold in colon cancer (P < 0.001). M3R
staining was also increased in 22 colon adenomas compared to adjacent normal
colon (P < 0.001). In contrast, M3R staining intensity was not increased in lymph
node or liver metastases. These findings suggest M3R expression plays an
important role in early progression and invasion of colon neoplasia but is less
important once tumors have spread.
PMID- 28416750
TI - Annonaceous acetogenins mediated up-regulation of Notch2 exerts growth inhibition
in human gastric cancer cells in vitro.
AB - BACKGROUND: Gastric cancer (GC) is a global health problem because of limited
treatments and poor prognosis. Annonaceous acetogenins (ACGs) has been reported
to exert anti-tumorigenic effects in cancer, yet the mechanism underlying its
effects on GC remains largely unknown. Notch signaling plays a critical role in
cell proliferation, differentiation and apoptosis. Therefore, it may contribute
to the development of GC. This study aims to explore the role of Notch2 in ACGs'
activities in GC cells. RESULTS: ACGs inhibited GC cells' viability in a dose
dependent manner and led to cell apoptosis and cell cycle arrest in G0/G1 phase
with an increased Notch2 expression. Additionally, Notch2 siRNA reduced ACGs
induced cell growth inhibition while Notch2 cDNA transfection did the opposite.
MATERIALS AND METHODS: ACGs were administrated in GC cells and cell proliferation
was assayed by MTS, cell apoptosis and cell cycle were detected by flow
cytometry. Additionally, the expression of Notch2 and the downstream target Hes1
were identified by Western blot. Furthermore, Notch2-siRNA transfection and
Notch2-cDNA were performed to investigate the role of Notch2 in the antitumor
effect of ACGs. CONCLUSIONS: Up-regulation of Notch2 by ACGs is a potential
therapeutic strategy for GC.
PMID- 28416751
TI - Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest
in AML in vitro and prolongs survival in vivo.
AB - Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and
ineligible to undergo intensive treatment, have a dismal prognosis. The small
molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like
kinase 1 and has shown remarkable anti-leukemic activity when combined with low
dose cytarabine. We have demonstrated that AML cells are highly vulnerable to
cell death in mitosis yet manage to escape a mitotic block through mitotic
slippage by sustained proteasome-dependent slow degradation of cyclin B.
Therefore, we tested whether interfering with mitotic slippage through proteasome
inhibition arrests and kills AML cells more efficiently during mitosis. We show
that therapeutic doses of bortezomib block the slow degradation of cyclin B
during a volasertib-induced mitotic arrest in AML cell lines and patient-derived
primary AML cells. In a xenotransplant mouse model of human AML, mice receiving
volasertib in combination with bortezomib showed superior disease control
compared to mice receiving volasertib alone, highlighting the potential
therapeutic impact of this drug combination.
PMID- 28416752
TI - CDKN2B gene rs1063192 polymorphism decreases the risk of glaucoma.
AB - The aim of this meta-analysis was to evaluate the association between cyclin
dependent kinase Inhibitor-2B (CDKN2B) gene rs1063192 polymorphism and glaucoma
risk. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs)
and 95% confidence intervals (CIs) were calculated by using fixed-effect or
random-effect models. A total of 14 case-control studies involving 11,316 cases
and 24,055 controls were included. Meta-analysis showed that CDKN2B gene
rs1063192 polymorphism was associated with a decreased risk of glaucoma.
Stratification analysis of ethnicity indicated that rs1063192 polymorphism
decreased the risk of glaucoma among Caucasians and Asians. Stratification
analysis by type of glaucoma revealed that rs1063192 polymorphism conferred a
protective factor of primary open-angle glaucoma (POAG) and non-POAG.
Stratification by source of controls uncovered an association between rs1063192
polymorphism and glaucoma in groups of population-based controls. In conclusion,
this meta-analysis indicates that CDKN2B gene rs1063192 polymorphism is
significantly associated with a decreased risk of glaucoma.
PMID- 28416753
TI - Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the
growth inhibitor lycorine in a mouse model of renal cell carcinoma.
AB - Renal cell carcinoma (RCC) management has undergone a major transformation over
the past decade; immune checkpoint inhibitors are currently undergoing clinical
trials and show promising results. However, the effectiveness of immune
checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited.
Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is
touted as a potential anti-cancer drug because of its demonstrative growth
inhibition capacity (induction of cell cycle arrest and inhibition of
vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy
with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4)
has improved outcomes in cancer patients. However, the anti-tumor efficacy of
combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated
a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine
RCC model. As a means of in vitro confirmation, we found that lycorine
hydrochloride inhibited the viability of various RCC cell lines. Furthermore,
luciferase-expressing Renca cells were implanted in the left kidney and the lung
of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride
and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and
luciferin-staining in tumor images. Importantly, the observed anti-tumor effects
of this combination were dependent on significantly suppressing regulatory T
cells while upregulating effector T cells; a decrease in regulatory T cells by
31.43% but an increase in effector T cells by 31.59% were observed in the
combination group compared with those in the control group). We suggest that a
combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic
option for RCC patients.
PMID- 28416755
TI - Efficacy and safety of BRAF inhibition alone versus combined BRAF and MEK
inhibition in melanoma: a meta-analysis of randomized controlled trials.
AB - Recent clinical studies have shown that combination therapy of BRAF and MEK
inhibition provides more survival benefit than BRAF inhibition monotherapy.
However, the adverse events due to BRAF and MEK inhibitors impact the physical
comfort and social life of patients. Thus, in this study we have undertaken a
meta-analysis of randomized controlled trials to compare the efficacy and adverse
events risk between monotherapy and combination therapy. We identified the
relevant studies by searching PubMed, EMBASE and Google scholar databases,
between the year January 2000 and May 2016. Based on the heterogeneity, the fixed
or random-effects models were employed to analyze the efficacy and the incidence
rate of adverse events. In addition, the subgroup analyses were conducted to
overcome the effects of heterogeneity. Finally, our study included five RCTs,
involving 1730 patients for this meta-analysis. The fixed-effects model
demonstrated that combination therapy of BRAF and MEK inhibition provided more
survival benefit in terms of ORR, PFS and OS (P < 0.00001). But, the combination
therapy also significantly increased the incidences of pyrexia, chills, vomiting,
chorioretinopathy, retinal detachment, hypertension, night sweats, increased
aspartate aminotransferase and creatine kinase levels (P < 0.05) as compared to
monotherapy. But, based on the significantly better survival outcomes, the
combined BRAF and MEK inhibition will obviously be the mainstay therapy for the
BRAF V600-mutant melanoma. However, a set of adverse events should be paid
attention when physicians consider combination therapy.
PMID- 28416756
TI - Prognostic significance of ZEB1 and ZEB2 in digestive cancers: a cohort-based
analysis and secondary analysis.
AB - BACKGROUND: Digestive cancers are common malignancies worldwide, however there
are few effective prognostic markers available. In this study we comprehensively
investigated the prognostic significance of ZEB1 and ZEB2 in digestive cancers.
METHODS: Electronic databases were searched and studies met the selection
criteria were included. Study information was recorded and quality assessment was
performed according to the REMARK guideline. Hazard ratios and its corresponding
95% confidence intervals were extracted and pooled. Sensitivity analyses,
subgroup analyses, cumulative meta-analyses and secondary analyses were also
performed to increase the stability and reliability of our results. RESULTS: 24
cohort studies were included in the study. High ZEB1 and ZEB2 levels predicted
poor overall survival, meanwhile high ZEB2 levels predicted poor disease free
survival for digestive cancer patients. From subgroup analyses we observed ZEB1
was found to be significantly associated with poor overall survival for patients
with pancreatic cancer, gastric cancer and colorectal cancer, while ZEB2 was
found to be significantly associated with poor overall survival for patients with
hepatocellular carcinoma and gastric cancer. Furthermore, by conducting secondary
analyses we confirmed both ZEB1 and ZEB2 played important roles in gastric cancer
prediction. In addition, we found high ZEB1 and ZEB2 expression were
significantly associated with depth of invasion, lymph node metastasis and TNM
stage in digestive cancer patients. CONCLUSIONS: The present study validated the
prognostic value and clinicopathological association of ZEB1 and ZEB2 in
digestive cancers, especially in gastric cancer.
PMID- 28416757
TI - Theranostic imaging of liver cancer using targeted optical/MRI dual-modal probes.
AB - The accurate preoperative detection and intraoperative navigation afforded by
imaging techniques have had significant impact on the success of liver cancer
surgeries. However, it is difficult to achieve satisfactory performance in both
diagnosis and surgical treatment processes using any single modality imaging
method. Here, we report the synthesis and characteristics of a novel dual
modality magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF)
probe and verify its feasibility in nude mouse models with liver cancer. The
probes are comprised of superparamagnetic iron oxide (SPIO) nanoparticles coated
with liposomes to which a tumor-targeted agent, Arg-Gly-Asp peptides (RGD), and a
NIRF dye (indocyanine green, ICG) have been conjugated. Specific targeting,
biodistribution, and the imaging ability of the probes for MRI-NIRF were
examined. Furthermore, we applied the dual-modality methodology toward the
preoperative diagnosis and intraoperative guidance of radical resection in mouse
models with both orthotopic liver tumors and intrahepatic tumor metastasis. The
study demonstrated that both MRI and fluorescent images showed clear tumor
delineation after probe injection (SPIO@Liposome-ICG-RGD). The contrast-to-noise
ratio obtained from MRI was 31.9 +/- 25.4 at post-injection for the preoperative
diagnosis, which is helpful for detecting small tumors (0.9 +/- 0.5 mm). The
maximum tumor to background ratio of NIRF imaging was 2.5 +/- 0.3 at 72 h post
injection for effectively capturing miniscule tumor lesions (0.6 +/- 0.3 mm)
intraoperatively. The novel MRI-NIRF dual modality probes are promising for the
achievement of more accurate liver tumor detection and resection.
PMID- 28416758
TI - Synergistic interactions between PLK1 and HDAC inhibitors in non-Hodgkin's
lymphoma cells occur in vitro and in vivo and proceed through multiple
mechanisms.
AB - Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the
histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B
cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo.
Exposure of DLBCL cells to very low concentrations of volasertib in combination
with belinostat synergistically increased cell death (apoptosis). Similar
interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib
resistant cells and primary lymphoma cells. Co-exposure to volasertib/belinostat
induced a marked increase in M-phase arrest, phospho-histone H3, mitotic errors,
cell death in M-phase, and DNA damage. Belinostat diminished c-Myc mRNA and
protein expression, an effect significantly enhanced by volasertib co-exposure. c
Myc knock-down increased DNA damage and cell death in response to volasertib,
arguing that c-Myc down-regulation plays a functional role in the lethality of
this regimen. Notably, PLK1 knock-down in DLBCL cells significantly increased
belinostat-induced M-phase accumulation, phospho-histone H3, gammaH2AX, and cell
death. Co-administration of volasertib and belinostat dramatically reduced tumor
growth in an ABC-DLBCL flank model (U2932) and a systemic double-hit lymphoma
model (OCI-Ly18), accompanied by a pronounced increase in survival without
significant weight loss or other toxicities. Together, these findings indicate
that PLK1/HDAC inhibition warrants attention as a therapeutic strategy in NHL.
PMID- 28416760
TI - The histone demethylase KDM3A regulates the transcriptional program of the
androgen receptor in prostate cancer cells.
AB - The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional
networks in a variety of biological processes such as spermatogenesis,
metabolism, stem cell activity, and tumor progression. We matched transcriptomic
and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic
control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring
histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation
effects of KDM3A. Combined assessment of histone demethylation events and gene
expression changes presented major transcriptional activation suggesting that
distinct oncogenic regulators may synergize with the epigenetic patterns by
KDM3A. Pathway enrichment analysis of cells with KDM3A knockdown prioritized
androgen signaling indicating that KDM3A plays a key role in regulating androgen
receptor activity. Matched ChIP-Seq and knockdown experiments of KDM3A in
combination with ChIP-Seq of the androgen receptor resulted in a gain of H3K9
methylation marks around androgen receptor binding sites of selected
transcriptional targets in androgen signaling including positive regulation of
KRT19, NKX3-1, KLK3, NDRG1, MAF, CREB3L4, MYC, INPP4B, PTK2B, MAPK1, MAP2K1,
IGF1, E2F1, HSP90AA1, HIF1A, and ACSL3. The cancer systems biology analysis of
KDM3A-dependent genes identifies an epigenetic and transcriptional network in
androgen response, hypoxia, glycolysis, and lipid metabolism. Genome-wide ChIP
Seq data highlights specific gene targets and the ability of epigenetic master
regulators to control oncogenic pathways and cancer progression.
PMID- 28416761
TI - Oncogenic senescence: a multi-functional perspective.
AB - Cellular senescence is defined as an irreversible growth arrest with the
acquisition of a distinctive secretome. The growth arrest is a potent anticancer
mechanism whereas the secretome facilitates wound healing, tissue repair, and
development. The senescence response has also become increasingly recognized as
an important contributor to aging and age-related diseases, including cancer.
Although oncogenic mutations are capable of inducing a beneficial senescence
response that prevents the growth of premalignant cells and promotes cancer
immune-surveillance, the secretome of senescent cells also includes factors with
pro-tumorigenic properties. On June 23rd and 24th, 2016, the Division of Cancer
Biology of the National Cancer Institute sponsored a workshop to discuss the
complex role of cellular senescence in tumorigenesis with the goal to define the
major challenges and opportunities within this important field of cancer
research. Additionally, it was noted how the development of novel tools and
technologies are required to accelerate research into a mechanistic understanding
of senescent cells in carcinogenesis in order to overcome the current limitations
in this exciting, yet ill-defined area.
PMID- 28416762
TI - Role of CD152 genetic polymorphisms in the susceptibility to breast cancer.
AB - BACKGROUND: The polymorphisms in cluster of differentiation 152 (CD152) gene have
been reported to be associated with breast cancer (BC), but relevant findings
were far from conclusive. Therefore, we carried out this meta-analysis to combine
those results for a clearer perspective on this issue. RESULTS: In our meta
analysis, a total of 8 eligible publications of 19 case-control studies were
selected, which totally contained 7,442 BC cases and 7,376 normal controls. Among
the five polymorphisms of CD152 gene, +49 G/A, -1661 A/G and -318 C/T
significantly increased the risk of BC under corresponding genetic comparisons;
while CT60 G/A polymorphism was negatively related to the cancer susceptibility.
In addition, -1772 T/C polymorphism of CD152 gene was not associated with the
development of BC. MATERIALS AND METHODS: Online databases and other sources were
searched for published studies on the relationship between BC susceptibility and
CD152 polymorphisms (+49 G/A, -1661 A/G, -1722 T/C, -318 C/T and CT60 G/A). The
strength of association was evaluated with pooled odds ratios (ORs) and their
corresponding 95% confidence intervals (95% CIs). Heterogeneity evaluation was
conducted via Q test. Sensitivity analysis was used to detect the stability of
our results. Begg's funnel plot and Egger's test were applied to investigate
publication bias among selected studies. CONCLUSIONS: The polymorphisms +49 G/A,
1661 A/G and -318 C/T may elevate the susceptibility to BC, but the polymorphism
CT60 G/A may offer protection against the cancer.
PMID- 28416759
TI - Beyond cell-cell adhesion: Plakoglobin and the regulation of tumorigenesis and
metastasis.
AB - Plakoglobin (also known as gamma-catenin) is a member of the Armadillo family of
proteins and a paralog of beta-catenin. Plakoglobin is a component of both the
adherens junctions and desmosomes, and therefore plays a vital role in the
regulation of cell-cell adhesion. Similar to beta-catenin, plakoglobin is capable
of participating in cell signaling in addition to its role in cell-cell adhesion.
In this context, beta-catenin has a well-documented oncogenic potential as a
component of the Wnt signaling pathway. In contrast, while some studies have
suggested a tumor promoting activity of plakoglobin in a cell/malignancy specific
context, it generally acts as a tumor/metastasis suppressor. How plakoglobin acts
as a growth/metastasis inhibitory protein has remained, until recently, unclear.
Recent evidence suggests that plakoglobin may suppress tumorigenesis and
metastasis by multiple mechanisms, including the suppression of oncogenic
signaling, interactions with various proteins involved in tumorigenesis and
metastasis, and the regulation of the expression of genes involved in these
processes. This review is primarily focused on various mechanisms by which
plakoglobin may inhibit tumorigenesis and metastasis.
PMID- 28416763
TI - Hormone receptor expression profiles differ between primary and recurrent high
grade serous ovarian cancers.
AB - Hormone receptor status assessment is necessary for selecting cancer patients who
might potentially benefit from endocrine therapy. To determine whether hormone
receptor status changes during tumor progression, we retrospectively examined 107
high-grade serous ovarian cancer (HGSC) patients with paired primary and
recurrent tumor specimens. Hormone receptor expression discordance rates between
primary and recurrent tumors were as follows: estrogen receptor (ER) 34.9%,
progesterone receptor (PR) 12.4%, androgen receptor (AR) 41.7%, follicle
stimulating hormone receptor 46.6%, luteinizing hormone receptor 50.5%, and
gonadotropin releasing hormone receptor 20.0%. Hormone receptor discordance was
not associated with patient survival. The proportion of the PR-ER+AR- subgroup,
which exhibited the worst prognosis, was higher in recurrent than primary tumor
specimens. Our study demonstrated that paired primary and recurrent HGSC
specimens exhibit differing hormone receptor profiles. Thus, to most effectively
identify patient-specific therapies, biomarker status re-assessment is required
for recurrent patients.
PMID- 28416764
TI - A recombinant fungal compound induces anti-proliferative and pro-apoptotic
effects on colon cancer cells.
AB - Finding intracellular pathways and molecules that can prevent the proliferation
of colon cancer cells can provide significant bases for developing treatments for
this disease. Ostreolysin (Oly) is a protein found in the mushroom Pleurotus
ostreatus, and we have produced a recombinant version of this protein (rOly).We
measured the viability of several colon cancer cells treated with rOly.
Xenografts and syngeneic colon cancer cells were injected into in vivo mouse
models, which were then treated with this recombinant protein.rOly treatment
induced a significant reduction in viability of human and mouse colon cancer
cells. In contrast, there was no reduction in the viability of normal epithelial
cells from the small intestine. In the search for cellular targets of rOly, we
showed that it enhances the anti-proliferative activity of drugs targeting
cellular tubulin. This was accompanied by a reduction in the weight and volume of
tumours in mice injected with rOly as compared to their respective control mice
in two in vivo models.Our results advance the functional understanding of rOly as
a potential anti-cancer treatment associated with pro-apoptotic activities
preferentially targeting colon cancer cells.
PMID- 28416765
TI - LoLoPicker: detecting low allelic-fraction variants from low-quality cancer
samples.
AB - INTRODUCTION: Although several programs are designed to identify variants with
low allelic-fraction, further improvement is needed, especially to push the
detection limit of low allelic-faction variants in low-quality, "noisy" tumor
samples. RESULTS: We developed LoLoPicker, an efficient tool dedicated to calling
somatic variants from next-generation sequencing (NGS) data of tumor sample
against the matched normal sample plus a user-defined control panel of additional
normal samples. The control panel allows accurately estimating background error
rate and therefore ensures high-accuracy mutation detection. CONCLUSIONS:
Compared to other methods, we showed a superior performance of LoLoPicker with
significantly improved specificity. The algorithm of LoLoPicker is particularly
useful for calling low allelic-fraction variants from low-quality cancer samples
such as formalin-fixed and paraffin-embedded (FFPE) samples.Implementation and
Availability: The main scripts are implemented in Python-2.7 and the package is
released at https://github.com/jcarrotzhang/LoLoPicker.
PMID- 28416766
TI - Notch3 overexpression enhances progression and chemoresistance of urothelial
carcinoma.
AB - Abnormal activation of Notch signaling is involved in the etiology of various
diseases, including cancer, but the association between Notch3 expression in
urothelial cancer and clinical outcome remains unclear, and the molecular
mechanisms underlying Notch3 signaling activation are not well defined. In this
study we examined 59 urothelial cancer patients and found that Notch3 was more
highly expressed in human urothelial cancer tissues than in non-tumorous bladder
tissue samples, with Notch3 overexpression being associated with poor clinical
outcome. Notch3 knockdown resulted in decreased proliferation of urothelial
cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition,
Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin.
Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC]
inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented
urothelial cancer cell proliferation, and induced cell cycle arrest. Taken
together, these data suggested that Notch 3 overexpression promotes growth and
chemoresistance in urothelial cancer.
PMID- 28416767
TI - The molecular heterogeneity of sporadic colorectal cancer with different tumor
sites in Chinese patients.
AB - PURPOSE: To assess the biological variability of clinical meaningful molecular
markers and their clinical correlations in Chinese patients with colorectal
cancer (CRC). MATERIALS AND METHODS: In this prospective observational study,
frequencies and clinico-pathological features of RAS and BRAFV600E mutations,
deficiency of DNA mismatch repair (dMMR) were evaluated in patients with
colorectal cancer staged I-IV. The molecular heterogeneity between right-sided
and left-sided colorectal cancers was studied in our series by classifying
patients with different mutations and dMMR status. RESULTS: Among 400 evaluable
patients, mutations in KRAS exon 2, exon 3 or 4, NRAS and BRAFV600E were detected
in 36%, 7.5%, 3.5% and 2.5%, respectively. RAS mutations were significantly
higher in metastatic CRCs (56.4% vs. 43.1%, p=0.015) and right-sided CRCs (62.5%
vs 41.7%, p=0.003). In 212 RAS wild-type patients, V600E mutation was higher in
older patients (9.5% vs. 2.2%, p=0.017), women (9.2% vs. 2.2%, p=0.021) and right
sided CRCs (10.5% vs. 3.4%, p=0.06). dMMR was detected in 7.75% of all stages of
CRCs, with the highest dMMR rate of 40% in stage II right-sided colon cancer.
CONCLUSIONS: By assessing the mutations and clinical correlations of RAS and BRAF
genes, and dMMR status, similar RAS mutation, dMMR frequency and lower BRAF
mutation was observed in Chinese patients compared to western patients. A
distinct molecular heterogeneity was found between patients with right-sided and
left-sided CRCs.
PMID- 28416768
TI - Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell
recruitment and CCR7+ tumor cell mobilization.
AB - Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is
expressed by cancer associated fibroblasts (CAFs). In malignant transformation,
PDPN is subjected to changes and its role is yet to be established. Here we show
that it is involved in modulating the activity of the CCL21/CCR7
chemokine/receptor axis in a hypoxia-dependent manner. In the present model,
breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor
for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The
impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3
cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor
environment. In addition to its known effect on migration, CCL21/CCR7 interaction
was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction
by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the
same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism
through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression
undergoes a reduction of adhesion, making it an anti-adhesion molecule in the
absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231
cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia
dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which
influence PDPN expression.
PMID- 28416769
TI - Nuclear organization of nucleotide excision repair is mediated by RING1B
dependent H2A-ubiquitylation.
AB - One of the major cellular DNA repair pathways is nucleotide excision repair
(NER). It is the primary pathway for repair of various DNA lesions caused by
exposure to ultraviolet (UV) light, such as cyclobutane pyrimidine dimers (CPDs)
and 6-4 photoproducts. Although lesion-containing DNA associates with the nuclear
matrix after UV irradiation it is still not understood how nuclear organization
affects NER. Analyzing unscheduled DNA synthesis (UDS) indicates that NER
preferentially occurs in specific nuclear areas, viz the nucleolus. Upon inducing
localized damage, we observe migration of damaged DNA towards the nucleolus.
Employing a LacR-based tethering system we demonstrate that H2A-ubiquitylation
via the UV-RING1B complex localizes chromatin close to the nucleolus. We further
show that the H2A-ubiquitin binding protein ZRF1 resides in the nucleolus, and
that it anchors ubiquitylated chromatin along with XPC. Our data thus provide
insight into the sub-nuclear organization of NER and reveal a novel role for
histone H2A-ubiquitylation.
PMID- 28416770
TI - NID1, a new regulator of EMT required for metastasis and chemoresistance of
ovarian cancer cells.
AB - Nidogen-1 (NID1) has been identified as a novel candidate diagnostic biomarker of
ovarian cancer in our previous study. Nevertheless, the role of NID1 in the
pathogenesis of ovarian cancer is unclear. In the present study, we demonstrated
that NID1 was a mesenchymal associated gene and its high expression was
significantly correlated with shorter overall survival of ovarian cancer
patients. The ectopic expression of NID1 in OVCAR-3 cells revealed a epithelial
mesenchymal transition (EMT) phenotype accompanied by enhancement of motility,
invasiveness and cisplatin resistance, whereas the knockdown of NID1 was
sufficient to convert HEY cells into epithelial phenotype with decreased
capability of motility, invasiveness and cisplatin resistance. Mechanistic
studies disclosed that NID1 activated ERK/MAPK signaling pathway to promote EMT.
Collectively, our findings have uncovered the molecular mechanisms of NID1 in
promoting ovarian cancer metastasis and chemoresistance, and provide a rationale
for the therapeutic potential of NID1 suppression in ovarian cancer.
PMID- 28416771
TI - XPG gene polymorphisms and cancer susceptibility: evidence from 47 studies.
AB - Xeroderma pigmentosum group G (XPG) is a single-strand-specific DNA endonuclease
that functions in the nucleotide excision repair pathway. Genetic variations in
XPG gene can alter the DNA repair capacity of this enzyme. We evaluated the
associations between six single nucleotide polymorphisms (SNPs) in XPG (rs1047768
T>C, rs2296147 T>C, rs2227869 G>C, rs2094258 C>T, rs751402 C>T, and rs873601 G>A)
and cancer risk. Forty-seven studies were identified in searches of the PubMed,
Scopus, Web of Science, China National Knowledge Infrastructure, and WanFang
databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were
calculated using a fixed or random effects model. We found that rs873601 G>A was
associated with an increased overall cancer risk (AA vs. GG: OR = 1.14, 95% CI =
1.06-1.24; GA/AA vs. GG: OR = 1.08, 95% CI = 1.02-1.15; A vs. G: OR = 1.06, 95%
CI = 1.02-1.10). In a stratified analysis, rs1047768 T>C was associated with an
increased risk of lung cancer, rs2227869 G>C was associated with a decreased risk
of cancer in population-based studies, and rs751402 C>T and rs873601 G>A were
associated with the risk of gastric cancer. Our data indicate that rs873601 G>A
is associated with cancer susceptibility.
PMID- 28416772
TI - DNA methylation of METTL7A gene body regulates its transcriptional level in
thyroid cancer.
AB - DNA methylation is the best-studied epigenetic mechanism for regulating gene
transcription and maintaining genome stability. Current research progress of
transcriptional regulation by DNA methylation mostly focuses on promoter region
where hypomethylated CpG islands are present transcriptional activity, as
hypermethylated CpG islands generally result in gene repression. Recently, the
DNA methylation patterns across the gene body (intragenic methylation) have
increasingly attracted attention towards their role in transcriptional regulation
and efficiency, due to the improvement of numerous genome-wide DNA methylation
profiling studies. However, the function and mechanism of gene body methylation
is still unclear. In this study, we revealed that the methylation level of
METTL7A, a seldom studied gene, was downregulated in thyroid cancer compared to
normal thyroid cells in vivo and in vitro. Moreover, we determined the
methylation level of one CpG site at the exon of the METTL7A gene body impacted
the transcriptional activity. Through generating a mutation of this CpG site (CG
to CC) of METTL7A exogenous vector artificially in vitro, we observed higher RNA
polymerase II recruitment and a declined enrichment of methyl-CpG binding protein
2 in gene body of METTL7A, in papillary thryoid cancer cells (BCPAP) compared to
normal thryoid cells. Finally, we revealed that EZH2, a subunit of polycomb
repressor complex 2, dominant in thyroid cancer, might be responsible for
regulating gene body methylation of METTL7A. Our study depicted the DNA
methylation patterns and the transcriptional regulatory mechanism of the gene
body in thyroid cancer. Furthermore, this study provides new insight into
potential future avenues, for therapies targeting cancer.
PMID- 28416773
TI - Changes in T-cell subpopulations and cytokine network during early period of
ibrutinib therapy in chronic lymphocytic leukemia patients: the significant
decrease in T regulatory cells number.
AB - B cell receptor (BCR) stimulation signal plays an important role in the
pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors
directed toward the BCR pathway are now the promising anti-leukemic drugs.
Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical
activity in CLL. It is reported that ibrutinib, additionally to directly
targeting leukemic cells, also inhibits the interactions of these cells with T
cells, macrophages and accessory cells. Assessment of these mechanisms is
important because of their non -direct anti-leukemic effects and to identify
possible side effects connected with long-term drug administration.The aim of
this study was to assess the in vivo effects of ibrutinib on T-cell
subpopulations and cytokine network in CLL. The analysis was performed on a group
of 19 patients during first month of ibrutinib therapy. The standard multicolor
flow cytometry and cytometric bead array methods were used for assessment of T
cell subsets and cytokines/chemokines, respectively.The data obtained indicates
that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine
network in CLL patients. Particularly, a significant reduction of T regulatory
cells in peripheral blood was observed. By targeting these populations of T cells
Ibrutinib can stimulate rejection of tumor cells by the immune system.
PMID- 28416774
TI - MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo
resistance via ZNRF2.
AB - Osteosarcoma (OS) is a prevalent cancer worldwide. MicroRNAs (miRNAs) play
critical roles in the growth, invasion and carcinogenesis of OS, whereas the
underlying mechanisms remain ill-defined. Here, we addressed these questions. We
detected significantly higher levels of ZNRF2, a ubiquitin ligase of the RING
superfamily, and significantly lower levels of miR-100 in the OS specimens,
compared to the paired normal bone tissues. The levels of ZNRF2 and miR-100
inversely correlated in the OS specimens. In addition, low miR-100 levels are
associated with poor prognosis of the OS patients. Either ZNRF2 overexpression or
miR-100 depletion increased in vitro OS cell growth and improved cell survival at
the presence of Doxorubicin. Mechanistically, with the help of bioinformatics
analysis and luciferase-reporter assay, we found that miR-100 might bind to the
3'-UTR of ZNRF2 mRNA to prevent its protein translation. Thus, our data suggest
that re-expression of miR-100 may inhibit OS cell growth and decrease OS cell
chemo-resistance.
PMID- 28416775
TI - Volatile organic compounds in gastrointestinal stromal tumour tissue originating
from patient-derived xenografts.
AB - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal
neoplasms of the gastrointestinal tract and localize mainly in the stomach or
small intestine. The metabolomic signatures of GISTs driven by different KIT gene
mutations remain undiscovered and unexplored. The main aim of this pilot study
was to determine and compare metabolomic profiles in GIST xenograft models with
different genetic backgrounds. Metabolomic profiling using gas chromatography
coupled with mass spectrometry followed by univariate and multivariate
statistical analyses was applied to select metabolites that differentiated the
GIST models studied. The significant differences observed in the metabolites were
mainly derived from glycolysis, the citric acid cycle and glutamine and lipid
metabolism. The obtained results may suggest variable metabolomic signatures of
tumours, possibly related to the different underlying, specific KIT gene
mutations and with potential implications for the biological behaviour and
natural course of this rare disease. This study constitutes a proof of concept in
GISTs and reveals the potential of the metabolomic approach in orphan
malignancies.
PMID- 28416777
TI - Intervention Therapy for Portal Vein Stenosis/Occlusion After Pediatric Liver
Transplantation.
AB - BACKGROUND The aim of this study was to investigate the outcomes and stent
implantation timing of portal vein stenosis intervention after pediatric liver
transplantation (pLT). MATERIAL AND METHODS The clinical data of 30 children with
post-liver transplantation portal vein stenosis/occlusion (PVS/O) between Jan
2008 and Jun 2015 were retrospectively analyzed. The successfully re-opened cases
used balloon angioplasty or stent implantation. SPSS13.0 software was used for
statistical analysis and paired t test of the pressure gradient at both ends of
the stenosis, diameter and flow rate within the stenosis, platelet count, and
albumin in the PVS children before and after balloon angioplasty, with p<0.05
considered as statistically significant. Among the 30 patients, 6 received a
stent implant in their first treatment, 22 received balloon angioplasty in their
first treatment, and in 2 the re-opening could not be achieved. RESULTS The
diameter of the stenotic segment, portal vein velocity, pressure gradient at both
ends of the stenosis, and platelet count in these children with portal vein
stenosis/occlusion (PVS/O) showed statistically significant differences when
comparing values before and after intervention (p<0.05), but albumin showed no
statistically significant difference (p>0.05). CONCLUSIONS Intervention therapy
for portal vein stenosis after pediatric liver transplantation (pLT-PVS) is a
safe and effective treatment, and patients with portal vein torsion, intimal
tearing, or long portal vein segment occlusion should undergo stent implantation.
PMID- 28416776
TI - Clinical Value of miR-101-3p and Biological Analysis of its Prospective Targets
in Breast Cancer: A Study Based on The Cancer Genome Atlas (TCGA) and
Bioinformatics.
AB - BACKGROUND MiR-101-3p can promote apoptosis and inhibit proliferation, invasion,
and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not
fully understood. Therefore, a comprehensive analysis of the target genes,
pathways, and networks of miR-101-3p in BC is necessary. MATERIAL AND METHODS The
miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA)
were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected
MCF-7 cells and scramble control cells was downloaded from Gene Expression
Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The
potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO)
and pathway and network analyses were constructed for the DEGs and predicted
genes. RESULTS In the TCGA data, a low level of miR-101-2 expression might
represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic
(HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER),
progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2),
and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis
(M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and
the 7924 potential target genes from the prediction databases. These genes were
related to transcription, metabolism, biosynthesis, and proliferation. The
results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt,
and chemokine signaling pathways. CONCLUSIONS MiR-101-1 and miR-101-2 may be
prospective biomarkers for the prognosis and diagnosis of BC, respectively, and
are associated with diverse clinical parameters. The target genes of miR-101-3p
regulate the development and progression of BC. These results provide insight
into the pathogenic mechanism and potential therapies for BC.
PMID- 28416778
TI - Steroid Pulse Therapy for De Novo Minimal Change Disease During Pregnancy.
AB - BACKGROUND Nephrotic syndrome occurs very rarely, in only about 0.01%-0.02% of
all pregnancies, and de novo minimal change disease during pregnancy is
especially rare. Nephrotic syndrome and, especially, minimal change disease are
highly responsive to steroids, and preterm labor may be avoidable if the maternal
condition is improved with steroid therapy. Therefore, prompt diagnosis and
proper management are critical to maternal and fetal outcome when severe
proteinuria occurs during pregnancy. CASE REPORT A 30-year-old pregnant Japanese
woman presented with systemic edema, oliguria, and severe proteinuria and
hypoalbuminemia at 25 weeks of gestation, although she was normotensive. The
patient had high urinary protein selectivity. Her illness was diagnosed as de
novo nephrotic syndrome with high steroid responsiveness rather than pre
eclampsia. She began steroid pulse therapy the day after admission. Complete
remission was confirmed after 3 weeks. The patient did not relapse during
pregnancy and delivered a healthy male baby at 37 weeks of gestation. A renal
biopsy at a relapse after delivery confirmed minimal change disease. CONCLUSIONS
In pregnant women with de novo minimal change disease, serious maternal and/or
fetal complications may occur if severe proteinuria and hypoalbuminemia are
unabated for an extended time. Evaluation of urinary protein selectivity is
noninvasive and useful for prediction of steroid responsiveness. Results of
urinary protein selectivity can be obtained earlier than results of renal biopsy.
Renal biopsy during pregnancy is not always necessary for initiation of steroid
therapy. Rapid initiation of steroid pulse therapy may enable quicker achievement
of remission and prevent serious perinatal complications.
PMID- 28416779
TI - Neuronal network models of epileptogenesis.
AB - Epilepsy is a chronic neurological condition, following some trigger,
transforming a normal brain to one that produces recurrent unprovoked seizures.
In the search for the mechanisms that best explain the epileptogenic process,
there is a growing body of evidence suggesting that the epilepsies are network
level disorders. In this review, we briefly describe the concept of neuronal
networks and highlight 2 methods used to analyse such networks. The first method,
graph theory, is used to describe general characteristics of a network to
facilitate comparison between normal and abnormal networks. The second, dynamic
causal modelling, is useful in the analysis of the pathways of seizure spread. We
concluded that the end results of the epileptogenic process are best understood
as abnormalities of neuronal circuitry and not simply as molecular or cellular
abnormalities. The network approach promises to generate new understanding and
more targeted treatment of epilepsy.
PMID- 28416780
TI - New onset epilepsy in the elderly: clinical, radiological and
electroencephalographic features and treatment responses.
AB - OBJECTIVE: To evaluate new onset epilepsy characteristics, etiology, radiological
and electroencephalographic features and to document treatment response in the
elderly. METHODS: This was a retrospective study carried out in King Fahd Medical
City, Riyadh, Kingdom of Saudi Arabia, from 2010 to 2013. Medical records were
searched to recruit patients. Hundred and nineteen patients were enrolled who
fulfill the inclusion criteria. Clinical data with respect to seizure semiology,
etiology, electroencephalographic findings, radiological findings, co
morbidities, and anti-epileptic drug (AED) therapy were assessed. RESULTS:
Cerebrovascular disease was the most common etiology, followed by occult
cerebrovascular disease (oCVD). Focal onset seizures were the most common
clinical presentation in this group of cohort. Electroencephalogram (EEG) showed
generalized slowing in majority of patients (45.5%), with 21.8% interictal
epileptiform activity. Patients required lower doses of AEDs to control seizures,
gain better seizure control. Common co-morbidities were hypertension and diabetes
mellitus. CONCLUSION: Patients presenting with LOE, should have search for any
other cerebrovascular risk factors. Further research is needed to determine the
prevalence of oCVD in LOE, and to investigate whether addressing cerebrovascular
risk factors in this cohort of patients can reduce the incidence of stroke.
PMID- 28416781
TI - Incidence, risk factors and outcomes of seizures occurring after craniotomy for
primary brain tumor resection.
AB - OBJECTIVE: To determine the incidence, risk factors and outcomes of early post
craniotomy seizures. METHODS: This was a retrospective cohort study of all
patients who underwent craniotomy for primary brain tumor resection (2002-2011)
and admitted postoperatively to the intensive care unit. The patients were
divided into 2 groups depending on the occurrence of seizures within 7 days.
RESULTS: One-hundred-ninety-three patients were studied: 35.8% had preoperative
seizure history and 16.6% were on prophylactic antiepileptic drugs (AEDs). Twenty
seven (14%) patients had post-craniotomy seizures. The tumors were mostly
meningiomas (63% for the post-craniotomy seizures group versus 58.1% for the
other group; p=0.63) and supratentorial (92.6% for the post-craniotomy seizures
versus 78.4% for the other group, p=0.09) with tumor diameter=3.7+/-1.5 versus
4.2+/-1.6 cm, (p=0.07). One (3.1%) of the 32 patients on prophylactic AEDs had
post-craniotomy seizures compared with 12% of the 92 patients not receiving AEDs
preoperatively (p=0.18). On multivariate analysis, predictors of post-craniotomy
seizures were preoperative seizures (odds ratio, 2.62; 95% confidence interval,
1.12-6.15) and smaller tumor size <4 cm (odds ratio, 2.50; 95% confidence
interval, 1.02-6.25). Post-craniotomy seizures were not associated with increased
morbidity or mortality. CONCLUSION: Early seizures were common after craniotomy
for primary brain tumor resection, but were not associated with worse outcomes.
Preoperative seizures and smaller tumor size were independent risk factors.
PMID- 28416782
TI - Assessment of atherosclerotic risk among patients with epilepsy on valproic acid,
lamotrigine, and carbamazepine treatment.
AB - OBJECTIVE: To compare the long-term effects of carbamazepine (CBZ), valproic acid
(VPA), and lamotrigine (LTG) as monotherapy on the markers of vascular risk.
METHODS: The present cross-sectional study was carried out at the Department of
Neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from
2012 to 2013. We selected 120 adult patients with epilepsy and 40 control
subjects. The patients with epilepsy were divided into 3 groups according to the
use of antiepileptic drugs (AEDs) (CBZ, n = 40; VPA, n = 40; and LTG, n = 40).
All participants' total cholesterol (TC), triglycerides (TG), low-density
lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL
c), high-density lipoprotein cholesterol (HDL-c), ratio of TC/HDL-c, ratio of LDL
c/HDL-c, body mass index (BMI), and blood pressure was determined. RESULTS: In
patients with epilepsy, CBZ and VPA treatment caused a noteworthy increase in the
concentrations of TG, TC, and LDL-c compared with LTG treatment and the control
group (p<0.001). The HDL-c significantly decreased in CBZ, VPA, and LTG-treated
patients as compared with controls (p<0.001). The ratio of LDL-c/HDL-c and TC/HDL
c significantly increased in VPA- and CBZ-treated groups compared with the LTG
treated, and control group, while the ratio was also considerably elevated in
patients treated with CBZ as compared with the patients treated with VPA. The
weight and BMI of the patients treated with AEDs were higher (p<0.01).
CONCLUSION: Patients with epilepsy on CBZ or VPA have changed vascular risk
markers that may lead to atherosclerosis, while LTG-treated patients have less
alteration in lipid profile.
PMID- 28416783
TI - Predictive and prognostic role of mean platelet volume in patients with first
ever acute ischemic stroke.
AB - OBJECTIVE: To investigate any possible effects of mean platelet volume (MPV) on
short-term stroke prognosis and functional outcome in patients with first-ever
acute ischemic stroke (FEAIS). METHODS: This retrospective cross-sectional study
included 798 FEAIS patients admitted to the emergency department of a tertiary
care hospital in Adiyaman, Turkey between January 2013 and June 2015. The data
were evaluated according to whether alive or dead, MPV levels, modified Rankin
scale (MRS) scores, National Institutes of Health Stroke Scale (NIHSS) scores.
The patients were divided into 3 groups based on MPV level as 4.4-7.4 fL, 7.5
10.4 fL, higher than 10.4 fL. RESULTS: A total of 250 patients with FEAIS were
included in the study. In both those who survived and those who died, the area
under the curve related to hospitalization days, time interval of venipuncture
(TIV), and MPV measurements was not statistically significant (p>0.05). The 3 MPV
groups showed no significant differences in terms of MRS score, median NIHSS
score, hospitalization, and TIV. In subgroups based on MRS scores, there were no
statistically significant differences according to median latency (p=0.087),
median hospitalization (p=0.394), TIV (p=0.201), and MPV levels (p=0.847).
Furthermore, there were no differences in MPV levels between the MRS based groups
(p=0.527). CONCLUSION: The results showed that MPV was not a significantly
associated and reliable marker for the prediction of prognosis or functional
outcome of FEAIS attack.
PMID- 28416784
TI - Longitudinal extensive transverse myelitis (LETM) in children: A twenty-year
study from Oman.
AB - OBJECTIVE: The data on children with diagnosis of idiopathic transverse myelitis
(ITM) was searched to find the pattern of myelitis in Oman. METHODS: A
retrospective study was carried out from January1995 to December 2014. Electronic
medical records and patient medical files were seen to get the complete data of
the children with ITM. This work was carried out at Sultan Qaboos University
hospital, Muscat, Oman. The ethical committee of the hospital had approved the
study. The diagnosis was based on the established criteria. Other causes of
myelopathy were excluded. RESULTS: 19 children with idiopathic transverse
myelitis were found. There were 18 out of 19 (94.6%) children with longitudinal
extensive transverse myelitis (LETM). CONCLUSION: Longitudinal transverse
extensive myelitis is the most common form of ITM in Oman.
PMID- 28416785
TI - A novel mutation in the glycine decarboxylase gene in patient with non-ketotic
hyperglycinemia.
AB - Non-ketotic hyperglycinemia (NKH) is a rare inborn error of metabolism and is
caused by a glycine cleavage system deficiency. Eighty-five percent of patients
present with the neonatal type of NKH, the infants initially develop lethargy,
seizures, and episodes of apnea, and most often death. Between 60-90% of cases
are caused by mutations in the glycine decarboxylase (GLDC). We believed that
more mutation reports especially for rare disease as NKH help to evaluate the
genotype-phenotype relationship in patients with GLDC. In this study, we describe
a case of a neonate admitted to intensive care unit with hypotonia, respiratory
failure, lethargy, poor feeding. Due to the history of 2 non-ketotic
hyperglycinemia diagnosed male siblings, molecular prenatal diagnosis in patient
was performed and a novel c.2963G>A (Arg998Gln) homozygous mutation within the
GLDC gene has been detected. We aimed to contribute to mutation knowledge pool of
GLDC gene with a novel mutation.
PMID- 28416786
TI - Basilar artery vasospasm after pretuncal non-aneurysmal subarachnoid hemorrhage
responding to milrinone.
AB - Pretruncal (perimesencephalic) non-aneurysmal subarachnoid hemorrhage (PNSAH) is
uniformly associated with an excellent outcome. Although cerebral vasospasm
remains a common complication of SAH and constitutes an important predictor of
outcome, in the setting of PNSAH, it is extremely rare. Preturnal non-aneurysmal
subarac refers to a subset of SAH patients with a characteristic pattern of
localized blood on CT of the head, normal cerebral angiography, and benign course
when compared to the aneurysmal SAH population. The presence of radiological or
even clinical vasospasm does not exclude the diagnosis of PNSAH. To our
knowledge, this is the first case of symptomatic cerebral vasospasm due to PNSAH
that responded to milrinone.
PMID- 28416787
TI - A family with hereditary cerebellar ataxia finally confirmed as Gerstmann
Straussler-Scheinker syndrome with P102L mutation in PRNP gene.
AB - Gerstmann-Straussler-Scheinker syndrome (GSS) is an exceedingly rare prion
disease. There are only 3 case reports of GSS in China. Here we report the first
GSS family in southern China. A 47-year-old female complained of unsteady gait
and dysarthria. Seven other individuals presented similar symptoms in 3
generations of her family, and all died 4-6 years after onset. To detect
causative mutations, we employed a gene analysis panel of hereditary diseases.
This revealed a P102L mutation in the prion protein gene (PRNP) gene, which is
commonly found in GSS featuring cerebellar ataxia. However, GSS is an uncommon
cause of hereditary cerebellar ataxia that might be overlooked because many
neurologists are unfamiliar with it. To avoid misdiagnosis in the patients with
hereditary cerebellar ataxia, GSS should be taken into account if other causes
are absent, especially in patients that have accompanying psychiatric symptoms
and a short survival time.
PMID- 28416788
TI - Characteristics of Arabic Websites with information on autism.
AB - OBJECTIVE: To explore the characteristics of Arabic websites with information on
autism spectrum disorder (ASD). METHODS: The word autism in Arabic was entered
into 2 popular search engines in September 2013 to locate the top 80 websites
featuring the term. Websites were sorted using 10 characteristics, previously
used to evaluate the characteristics of English websites with information on ASD.
RESULTS: Most websites were registered using a .com top-level domain (69%), were
an individual's site, forum, or blog (44%), and were updated after September 2012
(60%); they contained images or texts that seemed to persuade viewers to purchase
products (43%); they provided information with the name of author(s) (64%); they
described the basic characteristics of ASD; and they promoted various types of
treatments, most of which lack empirical support (63%). However, few websites
contained information with references to peer review resources (3%) or a warning
statement that such information should not replace the opinion of a qualified
professional (8%). CONCLUSION: Internet users may not find Arabic websites to be
reliable sources to obtain information on ASD. Given the increased use of the
internet, creation of websites that contain trusted information on ASD could
potentially aid parents in accessing available services, help them learn about
empirically validated interventions, and enable them to advocate for their
children's rights.
PMID- 28416789
TI - Pantothenate kinase-associated neurodegeneration.
PMID- 28416790
TI - A meta-analysis of cerebrospinal fluid visinin-like protein-1 in alzheimers
disease patients relative to healthy controls and mild cognitive impairment
patients.
AB - OBJECTIVE: To compare cerebrospinal fluid visinin-like protein-1 (CSF VLP-1) in
alzheimer's disease (AD) with that in healthy controls and mild cognitive
impairment (MCI) patients and find out possible sources of heterogeneity.
METHODS: "Visinin-like protein-1" and "alzheimer's disease" were employed to
search "PubMed", "Springer" and "Medline" databases until July 2016 and standard
mean difference (Std.MD) was calculated. Besides, subgroup analysis and meta
regression were performed to explore the possible heterogeneity sources. RESULTS:
Seven studies involved 1151 participants were pooled. The CSF VLP-1 in AD
patients was higher than that in healthy controls and MCI patients (pooled
Std.MD=0.81, 95% CI: [0.47, 1.16], p<0.00001). As shown by subgroup analysis,
population variations were one of heterogeneity sources. Meta-regression revealed
that Hedges's g of CSF VLP-1 was correlated with Std.MD of t-tau (r=0.560,
p=0.006) and amyloid beta42 (r=-0.386, p=0.013). CONCLUSION: The CSF VLP-1 in AD
patients is higher than that in healthy controls and MCI patients. The changes of
VLP-1 in AD patients relative to healthy controls and MCI patients is less
pronounced than that of core biomarkers, such as amyloid beta42, t-tau and p-tau.
Population variations, increasing t-tau and decreasing amyloid beta42 in AD
patients relative to healthy controls and MCI patients were the main sources of
heterogeneity.
PMID- 28416791
TI - Management of convulsive status epilepticus in children: an adapted clinical
practice guideline for pediatricians in Saudi Arabia.
PMID- 28416792
TI - Corrigendum: The OncoPPi network of cancer-focused protein-protein interactions
to inform biological insights and therapeutic strategies.
PMID- 28416793
TI - Seismic anisotropy of the D" layer induced by (001) deformation of post
perovskite.
AB - Crystallographic preferred orientation (CPO) of post-perovskite (Mg,Fe)SiO3 (pPv)
has been believed to be one potential source of the seismic anisotropic layer at
the bottom of the lower mantle (D" layer). However, the natural CPO of pPv
remains ambiguous in the D" layer. Here we have carried out the deformation
experiments of pPv-(Mg0.75,Fe0.25)SiO3 using synchrotron radial X-ray diffraction
in a membrane-driven laser-heated diamond anvil cell from 135 GPa and 2,500 K to
154 GPa and 3,000 K. Our results show that the intrinsic texture of pPv
(Mg0.75,Fe0.25)SiO3 should be (001) at realistic P-T conditions of the D" layer,
which can produce a shear wave splitting anisotropy of ~3.7% with VSH>VSV.
Considering the combined effect of both pPv and ferropericlase, we suggest that
50% or less of deformation is sufficient to explain the origin of the shear wave
anisotropy observed seismically in the D" layer beneath the circum-Pacific rim.
PMID- 28416794
TI - Stability of the frequent COPD exacerbator in the general population: A Danish
nationwide register-based study.
AB - : Exacerbation frequency is central in treatment strategies for chronic
obstructive pulmonary disease. However, whether chronic obstructive pulmonary
disease patients from the general population with frequent exacerbations continue
to have frequent exacerbations over an extended period of time is currently
unknown. In this study, we aimed to investigate the stability of the frequent
exacerbator in a population-based setting. To this end, we conducted a nationwide
register-based descriptive study with a 10-year follow-up period of chronic
obstructive pulmonary disease patients with at least one medically treated
exacerbation in 2003. Each subsequent year, we divided the population into
frequent, infrequent and non-exacerbators and quantified the flow between
categories. Further, we estimated the percentage of frequent exacerbators at
baseline who stayed in this category each year during a 5-year follow-up. We
identified 19,752 patients with chronic obstructive pulmonary disease and an
exacerbation in 2003. Thirty percent were frequent exacerbators. Overall, the
majority of exacerbators in 2003 were non-exacerbators in the following years
(60% in 2004 increasing to 68% in 2012). Approximately half of frequent
exacerbators in one year experienced a decrease in exacerbation frequency and had
either zero or one exacerbation in the subsequent year. This pattern was stable
throughout follow-up. During a 5-year follow-up period, a substantial proportion
(42%) of frequent exacerbators in 2003 had no additional years as frequent
exacerbators, while the minority (6%) remained in this category each year. In
conclusion, the rate of exacerbations shows considerable variation over time
among chronic obstructive pulmonary disease patients in the general population.
This might hold implications for chronic obstructive pulmonary disease treatment
guidelines and their practical application. CHRONIC OBSTRUCTIVE LUNG DISEASE:
VARIATIONS IN DISEASE PROGRESSION: Patients with chronic obstructive pulmonary
disease (COPD) who suffer from frequent exacerbations do not necessarily persist
with such severity over time. Exacerbations in COPD are defined by worsening
respiratory symptoms that result in changes to treatment, hospitalization and, at
worst, death. However, clarity is needed on whether frequent exacerbations is a
stable feature of some patients' disease. Mette Reilev at the University of
Southern Denmark and co-workers followed, over 10 years, 19,752 COPD patients
living in Denmark who suffered at least one exacerbation in 2003. By 2004, 60% of
patients were classed as infrequent or non-exacerbators, rising to 68% by 2012.
Very few patients remained "frequent exacerbators", suggesting the rate of
exacerbations changes considerably over time. This could hold implications for
COPD treatment and challenge assumptions made about disease progression.
PMID- 28416795
TI - Neutrophil stunning by metoprolol reduces infarct size.
AB - The beta1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size
in acute myocardial infarction (AMI) patients. The prevailing view has been that
metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol
reduces reperfusion injury by targeting the haematopoietic compartment.
Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol
acts during early phases of neutrophil recruitment by impairing structural and
functional rearrangements needed for productive engagement of circulating
platelets, resulting in erratic intravascular dynamics and blunted inflammation.
Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade
of PSGL-1, the receptor involved in neutrophil-platelet interactions, fully
abrogated metoprolol's infarct-limiting effects. The association between
neutrophil count and microvascular obstruction is abolished in metoprolol-treated
AMI patients. Metoprolol inhibits neutrophil-platelet interactions in AMI
patients by targeting neutrophils. Identification of the relevant role of ADRB1
in haematopoietic cells during acute injury and the protective role upon its
modulation offers potential for developing new therapeutic strategies.
PMID- 28416796
TI - Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell
surface.
AB - Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the
extracellular matrix. LOX overexpression is associated with poor cancer outcomes.
Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to
drive tumour progression. We show that LOX regulates EGFR by suppressing TGFbeta1
signalling through the secreted protease HTRA1. This increases the expression of
Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the
cell surface to facilitate its activation by EGF. We describe a pharmacological
inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and
delays the growth of primary and metastatic tumour cells in vivo. Thus, we show
that LOX regulates EGFR cell surface retention to drive tumour progression, and
we validate the therapeutic potential of inhibiting this pathway with the small
molecule inhibitor CCT365623.
PMID- 28416798
TI - Neurotransmission: Widening exocytosis.
PMID- 28416797
TI - Unification of de novo and acquired ibrutinib resistance in mantle cell lymphoma.
AB - The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high
response rates in B-cell lymphomas; however, a growing number of ibrutinib
treated patients relapse with resistance and fulminant progression. Using
chemical proteomics and an organotypic cell-based drug screening assay, we
determine the functional role of the tumour microenvironment (TME) in ibrutinib
activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop
ibrutinib resistance through evolutionary processes driven by dynamic feedback
between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing
the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin
beta1 signalling. Combinatorial disruption of B-cell receptor signalling and PI3K
AKT-mTOR axis leads to release of MCL cells from TME, reversal of drug resistance
and enhanced anti-MCL activity in MCL patient samples and patient-derived
xenograft models. This study unifies TME-mediated de novo and acquired drug
resistance mechanisms and provides a novel combination therapeutic strategy
against MCL and other B-cell malignancies.
PMID- 28416803
TI - Optical-helicity-driven magnetization dynamics in metallic ferromagnets.
AB - Recent observations of switching of magnetic domains in ferromagnetic metals by
circularly polarized light, so-called all-optical helicity dependent switching,
has renewed interest in the physics that governs the interactions between the
angular momentum of photons and the magnetic order parameter of materials. Here
we use time-resolved-vectorial measurements of magnetization dynamics of thin
layers of Fe, Ni and Co driven by picosecond duration pulses of circularly
polarized light. We decompose the torques that drive the magnetization into field
like and spin-transfer components that we attribute to the inverse Faraday effect
and optical spin-transfer torque, respectively. The inverse Faraday effect is
approximately the same in Fe, Ni and Co, but the optical spin-transfer torque is
strongly enhanced by adding a Pt capping layer. Our work provides quantitative
data for testing theories of light-material interactions in metallic ferromagnets
and multilayers.
PMID- 28416802
TI - RNA editing-dependent epitranscriptome diversity in cancer stem cells.
AB - Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of
their stem cell-like capacity to self-renew, survive and become dormant in
protective microenvironments. CSCs evolve during tumour progression in a manner
that conforms to Charles Darwin's principle of natural selection. Although
somatic DNA mutations and epigenetic alterations promote evolution, post
transcriptional RNA modifications together with RNA binding protein activity (the
'epitranscriptome') might also contribute to clonal evolution through dynamic
determination of RNA function and gene expression diversity in response to
environmental stimuli. Deregulation of these epitranscriptomic events contributes
to CSC generation and maintenance, which governs cancer progression and drug
resistance. In this Review, we discuss the role of malignant RNA processing in
CSC generation and maintenance, including mechanisms of RNA methylation, RNA
editing and RNA splicing, and the functional consequences of their aberrant
regulation in human malignancies. Finally, we highlight the potential of these
events as novel CSC biomarkers as well as therapeutic targets.
PMID- 28416804
TI - Cumulative culture can emerge from collective intelligence in animal groups.
AB - Studies of collective intelligence in animal groups typically overlook potential
improvement through learning. Although knowledge accumulation is recognized as a
major advantage of group living within the framework of Cumulative Cultural
Evolution (CCE), the interplay between CCE and collective intelligence has
remained unexplored. Here, we use homing pigeons to investigate whether the
repeated removal and replacement of individuals in experimental groups (a key
method in testing for CCE) alters the groups' solution efficiency over successive
generations. Homing performance improves continuously over generations, and later
generation groups eventually outperform both solo individuals and fixed
membership groups. Homing routes are more similar in consecutive generations
within the same chains than between chains, indicating cross-generational
knowledge transfer. Our findings thus show that collective intelligence in animal
groups can accumulate progressive modifications over time. Furthermore, our
results satisfy the main criteria for CCE and suggest potential mechanisms for
CCE that do not rely on complex cognition.
PMID- 28416806
TI - Elevated CYP2C19 expression is associated with depressive symptoms and
hippocampal homeostasis impairment.
AB - This corrects the article DOI: 10.1038/mp.2016.204.
PMID- 28416805
TI - A new inhibitor of the beta-arrestin/AP2 endocytic complex reveals interplay
between GPCR internalization and signalling.
AB - In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis,
beta-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical
signalling cascades. Distinguishing the respective contributions of beta-arrestin
recruitment to the receptor and beta-arrestin-promoted endocytosis in propagating
receptor signalling has been limited by the lack of selective analytical tools.
Here, using a combination of virtual screening and cell-based assays, we have
identified a small molecule that selectively inhibits the interaction between
beta-arrestin and the beta2-adaptin subunit of the clathrin adaptor protein AP2
without interfering with the formation of receptor/beta-arrestin complexes. This
selective beta-arrestin/beta2-adaptin inhibitor (Barbadin) blocks agonist
promoted endocytosis of the prototypical beta2-adrenergic (beta2AR), V2
vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect
beta-arrestin-independent (transferrin) or AP2-independent (endothelin-A)
receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated
ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and beta2AR,
supporting the concept of beta-arrestin/AP2-dependent signalling for both G
protein-dependent and -independent pathways.
PMID- 28416807
TI - A simplified protocol for differentiation of electrophysiologically mature
neuronal networks from human induced pluripotent stem cells.
AB - Progress in elucidating the molecular and cellular pathophysiology of
neuropsychiatric disorders has been hindered by the limited availability of
living human brain tissue. The emergence of induced pluripotent stem cells
(iPSCs) has offered a unique alternative strategy using patient-derived
functional neuronal networks. However, methods for reliably generating iPSC
derived neurons with mature electrophysiological characteristics have been
difficult to develop. Here, we report a simplified differentiation protocol that
yields electrophysiologically mature iPSC-derived cortical lineage neuronal
networks without the need for astrocyte co-culture or specialized media. This
protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise
from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of
114 neurons derived from three independent iPSC lines confirmed their
electrophysiological maturity, including resting membrane potential (-58.2+/-1.0
mV), capacitance (49.1+/-2.9 pF), action potential (AP) threshold (-50.9+/-0.5
mV) and AP amplitude (66.5+/-1.3 mV). Nearly 100% of neurons were capable of
firing APs, of which 79% had sustained trains of mature APs with minimal
accommodation (peak AP frequency: 11.9+/-0.5 Hz) and 74% exhibited spontaneous
synaptic activity (amplitude, 16.03+/-0.82 pA; frequency, 1.09+/-0.17 Hz). We
expect this protocol to be of broad applicability for implementing iPSC-based
neuronal network models of neuropsychiatric disorders.
PMID- 28416808
TI - Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in
mouse.
AB - Synapse development and neuronal activity represent fundamental processes for the
establishment of cognitive function. Structural organization as well as
signalling pathways from receptor stimulation to gene expression regulation are
mediated by synaptic activity and misregulated in neurodevelopmental disorders
such as autism spectrum disorder (ASD) and intellectual disability (ID).
Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been
described in male patients with X-linked ID and/or ASD. The structure of PTCHD1
protein is similar to the Patched (PTCH1) receptor; however, the cellular
mechanisms and pathways associated with PTCHD1 in the developing brain are poorly
determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that
binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1
is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted
of PTCH1, suggesting that both proteins are involved in distinct cellular
signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y)
induces global changes in synaptic gene expression, affects the expression of the
immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory
synaptic structure and neuronal excitatory activity in the hippocampus, leading
to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results
support that PTCHD1 deficiency induces a neurodevelopmental disorder causing
excitatory synaptic dysfunction.
PMID- 28416809
TI - Perisomatic changes in h-channels regulate depressive behaviors following chronic
unpredictable stress.
AB - Chronic stress can be a precipitating factor in the onset of depression.
Lentiviral-mediated knockdown of HCN1 protein expression and reduction of
functional Ih produce antidepressant behavior. However, whether h-channels are
altered in an animal model of depression is not known. We found that perisomatic
HCN1 protein expression and Ih-sensitive physiological measurements were
significantly increased in dorsal but not in ventral CA1 region/neurons following
chronic unpredictable stress (CUS), a widely accepted model for major depressive
disorder. Cell-attached patch clamp recordings confirmed that perisomatic Ih was
increased in dorsal CA1 neurons following CUS. Furthermore, when dorsal CA1 Ih
was reduced by shRNA-HCN1, the CUS-induced behavioral deficits were prevented.
Finally, rats infused in the dorsal CA1 region with thapsigargin, an irreversible
inhibitor of the SERCA pump, exhibited anxiogenic-like behaviors and increased
Ih, similar to that observed following CUS. Our results suggest that CUS, but not
acute stress, leads to an increase in perisomatic Ih in dorsal CA1 neurons and
that HCN channels represent a potential target for the treatment of major
depressive disorder.
PMID- 28416810
TI - The joint impact of cognitive performance in adolescence and familial cognitive
aptitude on risk for major psychiatric disorders: a delineation of four potential
pathways to illness.
AB - How do joint measures of premorbid cognitive ability and familial cognitive
aptitude (FCA) reflect risk for a diversity of psychiatric and substance use
disorders? To address this question, we examined, using Cox models, the
predictive effects of school achievement (SA) measured at age 16 and FCA-assessed
from SA in siblings and cousins, and educational attainment in parents-on risk
for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four
developmental patterns emerged. In the first, risk was predicted jointly by low
levels of SA and high levels of FCA-that is a level of SA lower than would be
predicted from the FCA. This pattern was strongest in autism spectrum disorders
and schizophrenia, and weakest in bipolar illness. In these disorders, a
pathologic process seems to have caused cognitive functioning to fall
substantially short of familial potential. In the second pattern, seen in the
internalizing conditions of major depression and anxiety disorders, risk was
associated with low SA but was unrelated to FCA. Externalizing disorders-drug
abuse and alcohol use disorders-demonstrated the third pattern, in which risk was
predicted jointly by low SA and low FCA. The fourth pattern, seen in eating
disorders, was directly opposite of that observed in externalizing disorders with
risk associated with high SA and high FCA. When measured together, adolescent
cognitive ability and FCA identified four developmental patterns leading to
diverse psychiatric disorders. The value of cognitive assessments in psychiatric
research can be substantially increased by also evaluating familial cognitive
potential.
PMID- 28416811
TI - Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to
chronic social defeat stress via regulating the stability of surface AMPARs.
AB - Both inflammatory processes and glutamatergic systems have been implicated in the
pathophysiology of mood-related disorders. However, the role of caspase-1, a
classic inflammatory caspase, in behavioral responses to chronic stress remains
largely unknown. To address this issue, we examined the effects and underlying
mechanisms of caspase-1 on preclinical murine models of depression. We found that
loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic
stress-induced depression-like behaviors, whereas overexpression of caspase-1 in
the hippocampus of wild-type (WT) mice was sufficient to induce depression- and
anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic
neurotransmission and decreased surface expression of glutamate receptors in
hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly,
pharmacological inhibition of caspase-1-interleukin-1beta (IL-1beta) signaling
pathway prevented the depression-like behaviors and the decrease in surface
expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
(AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both
depression- and anxiety-like behaviors can be mimicked by exogenous
intracerebroventricular (i.c.v.) administration of IL-1beta in both WT and
Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in
the caspase-1/IL-1beta axis facilitates AMPAR internalization in the hippocampus,
which dysregulates glutamatergic synaptic transmission, eventually resulting in
depression-like behaviors. These results may represent an endophenotype for
chronic stress-induced depression.
PMID- 28416812
TI - A new locus regulating MICALL2 expression was identified for association with
executive inhibition in children with attention deficit hyperactivity disorder.
AB - Impaired executive inhibition is a core deficit of attention deficit
hyperactivity disorder (ADHD), which is a common childhood-onset psychiatric
disorder with high heritability. In this study, we performed a two-stage genome
wide association study of executive inhibition in ADHD in Han Chinese. We used
the Stroop color-word interference test to evaluate executive inhibition. After
quality control, 780 samples with phenotype and covariate data were included in
the discovery stage, whereas 922 samples were included in the replication stage.
We identified one new significant locus at 7p22.3 for the Stroop word
interference time (rs11514810, P=3.42E-09 for discovery, P=0.01176 for
replication and combined P=5.249E-09). Regulatory feature analysis and expression
quantitative trait loci (eQTL) data showed that this locus contributes to MICALL2
expression in the human brain. Most genes in the network interacting with MICALL2
were associated with psychiatric disorders. Furthermore, hyperactive-impulsive
like behavior was induced by reducing the expression of the zebrafish gene that
is homologous to MICALL2, which could be rescued by tomoxetine (atomoxetine), a
clinical medication for ADHD. Our results suggested that MICALL2 is a new
susceptibility gene for executive inhibition deficiency related to hyperactive
impulsive behavior in ADHD, further emphasizing the possible role of
neurodevelopmental genes in the pathogenic mechanism of ADHD.
PMID- 28416814
TI - ISMEJ turns 10: tracking rapid progress in microbial ecology.
PMID- 28416813
TI - Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids
interactively modulate working memory-related hippocampal function in women: a
multimodal neuroimaging study.
AB - Preclinical evidence suggests that the actions of ovarian steroid hormones and
brain-derived neurotrophic factor (BDNF) are highly convergent on brain function.
Studies in humanized mice document an interaction between estrus cycle-related
changes in estradiol secretion and BDNF Val66Met genotype on measures of
hippocampal function and anxiety-like behavior. We believe our multimodal imaging
data provide the first demonstration in women that the effects of the BDNF
Val/Met polymorphism on hippocampal function are selectively modulated by
estradiol. In a 6-month pharmacological hormone manipulation protocol, healthy,
regularly menstruating, asymptomatic women completed positron emission tomography
(PET) and functional magnetic resonance imaging (fMRI) scans while performing the
n-back working memory task during three hormone conditions: ovarian suppression
induced by the gonadotropin-releasing hormone agonist, leuprolide acetate;
leuprolide plus estradiol; and leuprolide plus progesterone. For each of the
three hormone conditions, a discovery data set was obtained with oxygen-15 water
regional cerebral blood flow PET in 39 healthy women genotyped for BDNF Val66Met,
and a confirmatory data set was obtained with fMRI in 27 women. Our results, in
close agreement across the two imaging platforms, demonstrate an ovarian hormone
by-BDNF interaction on working memory-related hippocampal function (PET:
F2,37=9.11, P=0.00026 uncorrected, P=0.05, familywise error corrected with small
volume correction; fMRI: F2,25=5.43, P=0.01, uncorrected) that reflects
differential hippocampal recruitment in Met carriers but only in the presence of
estradiol. These findings have clinical relevance for understanding the
neurobiological basis of individual differences in the cognitive and behavioral
effects of ovarian steroids in women, and may provide a neurogenetic framework
for understanding neuropsychiatric disorders related to reproductive hormones as
well as illnesses with sex differences in disease expression and course.
PMID- 28416815
TI - In situ programming of leukaemia-specific T cells using synthetic DNA
nanocarriers.
AB - An emerging approach for treating cancer involves programming patient-derived T
cells with genes encoding disease-specific chimeric antigen receptors (CARs), so
that they can combat tumour cells once they are reinfused. Although trials of
this therapy have produced impressive results, the in vitro methods they require
to generate large numbers of tumour-specific T cells are too elaborate for
widespread application to treat cancer patients. Here, we describe a method to
quickly program circulating T cells with tumour-recognizing capabilities, thus
avoiding these complications. Specifically, we demonstrate that DNA-carrying
nanoparticles can efficiently introduce leukaemia-targeting CAR genes into T-cell
nuclei, thereby bringing about long-term disease remission. These polymer
nanoparticles are easy to manufacture in a stable form, which simplifies storage
and reduces cost. Our technology may therefore provide a practical, broadly
applicable treatment that can generate anti-tumour immunity 'on demand' for
oncologists in a variety of settings.
PMID- 28416816
TI - Scalable electrophysiology in intact small animals with nanoscale suspended
electrode arrays.
AB - Electrical measurements from large populations of animals would help reveal
fundamental properties of the nervous system and neurological diseases. Small
invertebrates are ideal for these large-scale studies; however, patch-clamp
electrophysiology in microscopic animals typically requires invasive dissections
and is low-throughput. To overcome these limitations, we present nano-SPEARs:
suspended electrodes integrated into a scalable microfluidic device. Using this
technology, we have made the first extracellular recordings of body-wall muscle
electrophysiology inside an intact roundworm, Caenorhabditis elegans. We can also
use nano-SPEARs to record from multiple animals in parallel and even from other
species, such as Hydra littoralis. Furthermore, we use nano-SPEARs to establish
the first electrophysiological phenotypes for C. elegans models for amyotrophic
lateral sclerosis and Parkinson's disease, and show a partial rescue of the
Parkinson's phenotype through drug treatment. These results demonstrate that nano
SPEARs provide the core technology for microchips that enable scalable, in vivo
studies of neurobiology and neurological diseases.
PMID- 28416817
TI - Controlling propagation and coupling of waveguide modes using phase-gradient
metasurfaces.
AB - Research on two-dimensional designer optical structures, or metasurfaces, has
mainly focused on controlling the wavefronts of light propagating in free space.
Here, we show that gradient metasurface structures consisting of phased arrays of
plasmonic or dielectric nanoantennas can be used to control guided waves via
strong optical scattering at subwavelength intervals. Based on this design
principle, we experimentally demonstrate waveguide mode converters, polarization
rotators and waveguide devices supporting asymmetric optical power transmission.
We also demonstrate all-dielectric on-chip polarization rotators based on phased
arrays of Mie resonators with negligible insertion losses. Our gradient
metasurfaces can enable small-footprint, broadband and low-loss photonic
integrated devices.
PMID- 28416819
TI - Cassava haplotype map highlights fixation of deleterious mutations during clonal
propagation.
AB - Cassava (Manihot esculenta Crantz) is an important staple food crop in Africa and
South America; however, ubiquitous deleterious mutations may severely decrease
its fitness. To evaluate these deleterious mutations, we constructed a cassava
haplotype map through deep sequencing 241 diverse accessions and identified >28
million segregating variants. We found that (i) although domestication has
modified starch and ketone metabolism pathways to allow for human consumption,
the concomitant bottleneck and clonal propagation have resulted in a large
proportion of fixed deleterious amino acid changes, increased the number of
deleterious alleles by 26%, and shifted the mutational burden toward common
variants; (ii) deleterious mutations have been ineffectively purged, owing to
limited recombination in the cassava genome; (iii) recent breeding efforts have
maintained yield by masking the most damaging recessive mutations in the
heterozygous state but have been unable to purge the mutation burden; such
purging should be a key target in future cassava breeding.
PMID- 28416820
TI - Contrasting evolutionary genome dynamics between domesticated and wild yeasts.
AB - Structural rearrangements have long been recognized as an important source of
genetic variation, with implications in phenotypic diversity and disease, yet
their detailed evolutionary dynamics remain elusive. Here we use long-read
sequencing to generate end-to-end genome assemblies for 12 strains representing
major subpopulations of the partially domesticated yeast Saccharomyces cerevisiae
and its wild relative Saccharomyces paradoxus. These population-level high
quality genomes with comprehensive annotation enable precise definition of
chromosomal boundaries between cores and subtelomeres and a high-resolution view
of evolutionary genome dynamics. In chromosomal cores, S. paradoxus shows faster
accumulation of balanced rearrangements (inversions, reciprocal translocations
and transpositions), whereas S. cerevisiae accumulates unbalanced rearrangements
(novel insertions, deletions and duplications) more rapidly. In subtelomeres,
both species show extensive interchromosomal reshuffling, with a higher tempo in
S. cerevisiae. Such striking contrasts between wild and domesticated yeasts are
likely to reflect the influence of human activities on structural genome
evolution.
PMID- 28416821
TI - Pathogenic variants that alter protein code often disrupt splicing.
AB - The lack of tools to identify causative variants from sequencing data greatly
limits the promise of precision medicine. Previous studies suggest that one-third
of disease-associated alleles alter splicing. We discovered that the alleles
causing splicing defects cluster in disease-associated genes (for example,
haploinsufficient genes). We analyzed 4,964 published disease-causing exonic
mutations using a massively parallel splicing assay (MaPSy), which showed an 81%
concordance rate with splicing in patient tissue. Approximately 10% of exonic
mutations altered splicing, mostly by disrupting multiple stages of spliceosome
assembly. We present a large-scale characterization of exonic splicing mutations
using a new technology that facilitates variant classification and keeps pace
with variant discovery.
PMID- 28416823
TI - [Identification of a new pro-invasion factor in tumor microenvironment: progress
in function and mechanism of extracellular ATP].
AB - Up to 90% of all cancer related morbidity and mortality can be attributed to
metastasis. In recent years the study of tumor microenvironment, its cellular and
molecular components, and how they can affect neoplastic progression toward
metastasis, has become a hot focus in cancer research. Accumulated evidence shows
that the formation of metastasis is a multi-step sequential process, in which,
the tumor cells continuously interact with the host microenvironment. Host
derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines,
etc. together with different types of host cells, play important roles in the
tumor progression towards metastasis. The interaction between the tumor cells and
host microenvironment determines the fate of metastasis. The reveal of this
interaction mechanism provides us an opportunity to find effective mode of
interference and develop novel anti-metastasis drugs. In this review, we have
summarized our work on a new pro-invasion factor identified in tumor
microenvironment and how it affects tumor invasion and metastass. Adenosine
triphosphate (ATP), the key intracellular energy currency, accumulates within the
tumor microenvironment and is closely involved in cancer cell metabolism and in
antitumor immunity. The established role of ATP as a growth modulator and a
proinflammatory mediator endues ATP and other purines with potential players in
host-tumor interaction. Our study demonstrated that extracellular ATP stimulated
human cancer invasion in in vitro tests. Increased migration and invasive ability
across Matrigel was observed in some human carcinoma cell lines, including the
prostate, breast, colon, melanoma and lung, when stimulated with ATP or its
analogues. ATP enhanced the motility of cancer cells via increasing the amount
and length of lamellipodia and filopodia, which were necessary for the cell
motility. Significant increase in Rac1 and Cdc42 activities was observed. Using
cDNA microarray we found that the expression of a panel of invasion/metastasis
related genes was significantly changed, including the increased expression of
interleukin (IL)-8 and matrix metalloproteinase-3 (MMP-3) after ATP treatment.
Changes of some epithelial-mesenchymal transition (EMT)-related factors were also
observed, including the increase of snail, decrease of E-cadherin and claudin-1.
Multiple P2Y receptors subtypes were expressed on tumor cells, but P2Y2 and P2X7
receptors were found to be mainly responsible for the pro-invasive effect of ATP.
Down-regulation of either P2Y2 or P2X7 abolished ATP effect on cancer invasion
and expression of EMT/invasion-related genes. Further, we found that P2Y2
receptor trans-activated with epidermal growth factor receptor (EGFR) and co
activated extracellular regulated protein kinases (ERK1/2) signaling pathway,
which was involved in regulating expression of EMT and other related genes. In
nude mice experiment, the pro-invasive effect of ATP was further confirmed. In
summary, our results reveal that ATP is a potential pro-invasive factor in tumor
microenvironment. P2Y2/P2X7 receptors act as a mediator in the regulation of ATP
induced EMT and invasion of cancer cells. Given that tumor microenvironment is
rich in ATP and other purines, we hypothesize that ATP might be a potential
invasion stimulator in tumor microenvironment. Blocking ATP receptor might be a
therapeutic target on cancer.
PMID- 28416822
TI - Identification of six new genetic loci associated with atrial fibrillation in the
Japanese population.
AB - Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To
investigate genetic loci associated with atrial fibrillation in the Japanese
population, we performed a genome-wide association study (GWAS) that included
8,180 atrial fibrillation cases and 28,612 controls with follow-up in an
additional 3,120 cases and 125,064 controls. We replicated previously reported
loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2,
NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated
with atrial fibrillation in the Japanese population after comparing our data to
those from individuals of European ancestry, suggesting that there might be
different genetic factors affecting susceptibility across ancestry groups. Our
study discovered variants in the HAND2, KCND3 and NEBL genes, which are relevant
to atrial fibrillation susceptibility. The involvement of PPFIA4 and SH3PXD2A in
axon guidance also suggested a role in disease pathogenesis. Our findings may
contribute to a better understanding of atrial fibrillation susceptibility and
pathogenesis.
PMID- 28416824
TI - [Gait analysis at the early stage after direct anterior approach in total hip
arthroplasty].
AB - OBJECTIVE: To evaluate the result of operation and gait analysis at the early
stage after direct anterior approach (DAA) in total hip arthroplasty (THA).
METHODS: In this study, 20 patients who suffered from necrosis of femoral head or
developmental dysplasia of the hip were scheduled to undergo THA. The basic
information and visual analogue scale (VAS) score, Harris score before and after
surgery were recorded. All of the patients finished the gait analysis before the
surgery and 6 weeks and 12 weeks after the surgery, the data were compared with
those of normal adult people. RESULTS: Their hospital stay after the operation
was 3.3 d, the VAS score after the operation was no more than 4 points, the
positions of prosthesis were satisfactory, and there was no dislocation. The gait
analysis results contained step speed, stride, the range of motion (ROM) of hip
and knee. The step speed before the surgery (preoperation, Pre) was 0.64 m/s, 6
weeks after the surgery (6W) was 0.77 m/s, 12 weeks after the surgery (12W) was
1.07 m/s, and the control group was 1.19 m/s. The stride at Pre, 6W, 12W, and
control group were 43.15 steps/min, 51.42 steps/min, 55.52 steps/min, and 57.15
steps/min, respectively. The ROM of hip joint at Pre, 6W, 12W, and control group
were 31.00 degrees , 39.62 degrees , 40.40 degrees , and 45.67 degrees ,
respectively. The ROM of knee joint at Pre, 6W, 12W, and control group were 50.52
degrees , 59.28 degrees , 67.29 degrees , and 70.42 degrees , respectively. The
results of the gait analysis showed that the gait recovery after the direct
anterior total hip arthroplasty was very fast and at the 12th week after surgery
the gait of the patients was close to the normal adult people. CONCLUSION: The
direct anterior approach is one of the choosable approach of the THA, and this
kind of surgery has a better recovery of gait after the operation, and at the end
of 12 weeks after the surgery the gait is very close to the normal adult people.
But we also need more studies to prove this conclusion.
PMID- 28416818
TI - Large-scale analyses of common and rare variants identify 12 new loci associated
with atrial fibrillation.
AB - Atrial fibrillation affects more than 33 million people worldwide and increases
the risk of stroke, heart failure, and death. Fourteen genetic loci have been
associated with atrial fibrillation in European and Asian ancestry groups. To
further define the genetic basis of atrial fibrillation, we performed large
scale, trans-ancestry meta-analyses of common and rare variant association
studies. The genome-wide association studies (GWAS) included 17,931 individuals
with atrial fibrillation and 115,142 referents; the exome-wide association
studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases
and 132,086 referents. We identified 12 new genetic loci that exceeded genome
wide significance, implicating genes involved in cardiac electrical and
structural remodeling. Our results nearly double the number of known genetic loci
for atrial fibrillation, provide insights into the molecular basis of atrial
fibrillation, and may facilitate the identification of new potential targets for
drug discovery.
PMID- 28416825
TI - [Comparison of efficacy and safety between the anterior and the posterior
approaches to total hip arthroplasty].
AB - OBJECTIVE: To compare the efficacy and safety between direct anterior approach
(DAA) and posterior approach (PA) in total hip arthroplasty. METHODS: This study
evaluated postoperative results of 92 consecutive total hip arthroplasties
performed by a single surgeon; 44 from the DAA, and 48 from PA. The age, body
mass index, operation time, blood loss, hospital stay, positioning of the
artificial hip, postoperative Harris score and postoperative complications were
recorded and analyzed. RESULTS: Both the average age of the patients separately
(58.0+/-11.9) years in DAA group and (61.0+/-10.4) years in PA group and the body
mass index (25.1+/-3.7) in DAA group and (24.7+/-3.3) in PA group, showed no
significant difference between the two groups. The DAA group had significantly
reduced the hospital stay (3.8+/-1.7) days vs.(4.9+/-2.3) days for the PA group
(P<0.05) and operation time was (76.0+/-17.4) min in DAA group, and (71.0+/-14.3)
min in PA group (P>0.05). The amount of blood loss: in group DAA (238.0+/-55.3)
mL, and in group PA (387.0+/-61.2) mL (P<0.05). There was no statistical
difference in the positioning of the artificial hip: the cup anteversion in DAA
group and PA group was 17.3 degrees +/-5.3 degrees vs. 18.6 degrees +/- 5.1
degrees , the cup inclination was 38.5 degrees +/-5.7 degrees vs. 37.7 degrees
+/-5.2 degrees . In DAA group, there was significantly less use of assistive
devices [(24.6+/-7.8) d vs. (31.7+/-10.2) d, P<0.05], and the pain was
significantly lower. Harris score at the end of 6 weeks of the follow-up: in DAA
group 85.7+/-5.4, and in PA group 81.3+/-6.1 (P<0.05); at the end of the last
follow-up: in DAA group 93.4+/-4.7, and in PA group 92.3+/-5.3 (P>0.05).
Complications were encountered in the two groups. There were two intraoperative
complications (4.4%), 1 great trochanter fracture and 1 lateral cutaneous nerve
injury in DAA group. No dislocation was observed in DAA group. One dislocations
and 1 groin pain were recorded in PA group. No prosthesis loosening, deep vein
thrombosis, sciatic nerve injury and other complications occurred in the two
groups. CONCLUSION: Total hip arthroplasty using the anterior approach allows for
superior recovery and better stability.
PMID- 28416826
TI - [Surgical technique and early clinical outcomes of direct anterior approach to
total hip arthroplasty].
AB - OBJECTIVE: To describe the surgical technique of direct anterior approach to
total hip arthroplasty and to report the early clinical outcomes. METHODS: A
series of 100 consecutive, unselected patients who had 116 primary total hip
arthroplasty surgeries (16 bilateral) done through direct anterior approach from
March 11 2015 to June 21 2016 was reviewed. There were 50 male patients and 50
female patients. The average patient age was 51 years, and the average body mass
index was 24.69 kg/m2. The preoperative diagnosis included avascular necrosis of
femoral head, hip osteoarthritis, osteoarthritis secondary to acetabular
dysplasia, sequelae of hip old infection, ankylosing spondylitis, rheumatoid
arthritis and avascular necrosis of femoral head after cannulated screws fixation
of femoral neck fracture. There were 7 hips which had surgical history prior to
the index hip arthroplasty, including 3 cases with bone graft treatment for
avascular necrosis of femoral head through Smith-Peterson approach, 2 cases with
acetabular shelf procedures for acetabular dysplasia through Smith-Peterson
approach, and 2 cases with cannulated screws fixation for femoral neck fracture
(internal fixation residual). All were uncemented hips. The stems used in this
study included 67 Triloc stems (DePuy company, USA), 45 Corail stems (DePuy
company, USA), 2 Accolade stems (Stryker company, USA), 1 Synergy stem (Smith
Nephew company, USA) and 1 Polarstem (Smith-Nephew company, USA). RESULTS: The
average follow up period was 8.5 months, the average incision scar length was 10
cm, and the average postoperative Harris score was 93.62. There was 95%
postoperative leg length discrepancy within 3 mm. The average cup inclination
angle was 38.7 degrees with 94.8% in the range of 30 degrees to 50 degrees .
The average cup anteversion angle was 14.3 degrees with 94.2% within the target
range of 5 degrees to 25 degrees .The were 15 (12.9%) operative complications,
including two femoral perforations (changing stem from Triloc to Corail), three
calcar fractures (treated with cerclage wires), four greater trochanter fractures
(2 were treated wire tension band, and 2 nondisplaced fractures untreated), one
deep infection (debridement and retaining of the prothesis), one superficial
infection (debridement), one hematoma and three wound healing complications
(debridement). All the complications were successfully treated without any
sequelae at the end of the latest follow-up. There was no postoperative
dislocation. There was no major nerve and vascular injuries. There were 35 cases
(30.2%) reporting symptoms of lateral femoral cutaneous nerve palsy. CONCLUSION:
Direct anterior approach to total hip arthroplasty allows accurate and
reproducible cup orientation positioning and leg length restoration and decreases
the risk of postoperative dislocation, which is helpful for early rapid
postoperative recovery.
PMID- 28416827
TI - [Comparison of the effects of total hip arthroplasty via direct anterior approach
and posterolateral piriformis-sparing approach].
AB - OBJECTIVE: To compare the clinical effects of direct anterior approach (DAA) and
posterolateral piriformis-sparing approach (Mis-PLA) for minimally invasive
surgery of total hip arthroplasty. METHODS: The patients who had total hip
arthroplasty from March 2015 to February 2016 were randomly divided into 2
groups: DAA group and Mis-PLA group. In the study, 43 patients (45 hips) were
performed with total hip replacement via the direct anterior approach (DAA
group). As comparison, 39 patients (42 hips) were performed with total hip
replacement via the posterolateral piriformis-sparing approach (Mis-PLA group) at
the same period. DAA group: 27 male patients (27 hips), and 16 female patients
(18 hips), with an average age of (57.4+/-7.3) years, preoperative Harris score
(41.4+/-8.7), body mass index (BMI) (24.3+/-2.2) kg/m2; Mis-PLA group: 25 male
patients (26 hips), 14 female patients (16 hips), with an average age of (59.2+/
7.3) years, preoperative Harris score (39.6+/-8.4), BMI (24.7+/-2.5) kg/m2. The
length of incision, operation time, blood loss, postoperative Harris score were
observed and specially the hip functional recovery was fully assessed. RESULTS:
(1) All the incisions healed by first intention. No complications were found in
both groups. The length of incision:DAA group: (9.2+/-0.7) cm and Mis-PLA group:
(9.5+/-0.6) cm. No statistical significant differences were found (P=0.053). The
operation time:DAA group (74.3+/-10.1) min and Mis-PLA group (37.5+/-4.3) min,
which showed statistically significant differences (P<0.01). Blood loss: DAA
group (229.6+/-79.2) mL and Mis-PLA group (215.7+/-56.0) mL. No statistical
significant differences were found (P=0.366). (2) The patients in both groups
were followed up for 6-12 months. The Harris hip scores for 6 weeks' follow-up:
(85.5+/-4.1) in DAA group and (79.0+/-4.4) in Mis-PLA group, which indicated
statistically significant differences (P<0.01). The Harris scores for the 6-month
follow-up: (94.3+/-2.7) in DAA group and (95.2+/-1.9) in Mis-PLA group. No
statistically significant differences were found (P=0.125). The basic daily hip
function analysis for the 6-week follow-up: walking speed: no statistically
significant differences were found between the two groups (P=0.298); Climbing
stairs: Mis-PLA group' outcome was better than DAA group's with statistical
differences (P=0.047); Circling, sitting and wearing shoes and socks: outcomes in
DAA group exceeded Mis-PLA group's with statistically significant differences
(P<0.01, P=0.016, P<0.01). CONCLUSION: Total hip arthroplasty through either DAA
or Mis-PLA approaches could result in very satisfactory clinical effect.
Comparing with DAA, Mis-PLA requires less operation time, shorter learning
curve,which indicates that it is a relatively safer approach. The advantages of
total hip arthroplasty through direct anterior approach lie in less positional
limitation in the early stage of postoperative period, as well as a faster
recovery of hip function.
PMID- 28416828
TI - [Application of bilateral direct anterior approach total hip arthroplasty: a
report of 22 cases].
AB - OBJECTIVE: To analyze the operation technique and the methods to avoid early
complications on the learning curve for bilateral direct anterior approach (DAA)
total hip arthroplasty (THA). METHODS: We retrospectively studied a series of
continued cases with bilateral avascular necrosis of the femoral head (AVN) or
degenerative dysplastic hip and rheumatoid arthritis that were treated by DAA THA
in Beijing Jishuitan Hospital. A total of 22 patients with 44 hips were analyzed
from June 2014 to August 2016 in this study. There were 17 males and 5 females,
and the median age was 48 years (range: 34-67 years). All the surgery was done by
DAA method by two senior surgeons. The clinic characters, early surgery treatment
results and complications were analyzed. RESULTS: We used the cementless stems in
all the cases. The average operating time was (167+/-23) min; the average blood
loss was (775+/-300) mL;the blood transfusion was in average (327+/-341) mL; the
wound drainage in average was (111+/-73) mL. Most of the patients could move out
of the bed by themselves on the first day after operation, 5 patients could walk
without crutches on the first operating day, and 13 patients could squat on the
third days after operation. The patients were discharged averagely 4 days after
operation. We followed up all the patients for averagely 16 months (range: 8-24
months). There was no loosening or failure case in the latest follow up. In the
study, 2 patients had great trochanter fracture, 2 patients had thigh pain, 4
patients had lateral femoral cutaneous nerve palsy, and 3 patients had muscle
damage. The Harris scores were improved from 29+/-8 preoperatively to 90+/-3
postoperatively (P<0.01). CONCLUSION: The DAA THA can achieve faster recovery and
flexible hip joint after operation. However it is a kind of surgery with high
technique demanding. Carefully selected patients, and skilled technique, can help
the surgeon avoid the early complications. It is associated with high
complication rate in the learning curve for bilateral DAA THA.
PMID- 28416829
TI - [Clinical characteristics and prognosis of cultured negative pyogenic
spondylitis].
AB - OBJECTIVE: There are limited data describing the clinical characteristics and
prognosis of culture negative pyogenic spondylitis. The aim of this study was to
investigate the treatment, prognosis and clinical characteristics of culture
negative pyogenic spondylitis. METHODS: A retrospective study reviewed 74
patients who were diagnosed with spondylitis in Peking University First Hospital
from January 2010 to December 2015. A total of 27 patients suffered from pyogenic
spondylitis. According to the pathogenic culture results, the patients were
divided into two groups: culture negative group and culture positive group. The
clinical characteristics and treatment outcomes between the two groups were
compared. RESULTS: The elder were more vulnerable to pyogenic spondylitis, and of
the 27 patients, 12 patients were female and 15 male. All patients had no history
of administration of antibiotics prior to obtaining culture samples. A causative
germ was identified in 14/27 patients (51.9%) with Staphylococcus aureus being
the most common pathogen. There was no significant difference between the two
groups in the patient's age, gender, visual analogue score (VAS), predisposing
factor, clinical symptom, sign and spinal segment (P>0.05). Erythrocyte
sedimentation rate (ESR) (P=0.056) and C-reactive protein (CRP) (P=0.040) of
culture negative group were lower in contrast to culture positive group. The
incidence of vertebral abscess in culture negative group was higher than in
culture positive group (P=0.046). After treatment, ESR dropped almost equally in
both groups, and CRP dropped faster in the culture positive group (P=0.192). At
last, there was no significant difference between the two groups in hospital
stay, pain relief, open debridement operation rate, and recurrence rate of
infection. CONCLUSION: ESR and CRP of the culture negative patient were lower
than those of the culture positive patient, and the incidence rate of
paravertebral abscess was higher than that of the culture positive patient. After
administration of antibiotics, there was no significant difference between the
two groups in duration of antibiotics, open debridement operation rate and
recurrence rate of infection. So, culture negative may not necessarily be a
negative prognostic factor for pyogenic spondylitis. However, we should watch out
for the drug resistant bacteria or double infection, due to the long term use of
wide-spectrum antibiotic in culture negative patients.
PMID- 28416830
TI - [Analysis on the causes of unscheduled suspensions of knee and hip arthroplasty].
AB - OBJECTIVE: To analyze and summarize the causes of unscheduled suspension of knee
and hip arthroplasty and to provide the method for optimizing the patient's
preoperative management and improving the efficiency of medical resources as well
as the patient's satisfaction. METHODS: The data for this report was
retrospectively collected from September 2013 to August 2014 in our hospital,
from cases of knee and hip arthroplasty that were suspended before the scheduled
operation time. Acquisition data from the collected cases including the patients'
gender, age and the surgical procedure. At the same time, the suspension reasons
were recorded and analyzed. All the decisions of suspension was made by the
surgeons and the anesthesiologists according to the abnormal result of
preoperative examinations, after communicating with the patients and their
families and obtaining their understandings. RESULTS: In the collecting period,
our department scheduled 1 146 cases of knee and hip arthroplasty, among which 1
003 were completed, 143 suspended (12.5% suspension rate). Among the causes of
suspension, the top four common causes were cardiovascular disease (44/143, 31%),
other infections (20/143, 14%), bacteriuria (18/143, 13%) and inappropriate
surgical indication (16/143, 11%). Other causes include surgeon's reason, Blood
system abnormalities, high inflammatory index, deep vein thrombosis, other
diseases uncontrolled, abnormal liver function and poor diabetes mellitus
control, etc. For the rate of suspension, there was no significant difference
between the patients with different genders (male: 15.0%, and female: 11.7%,
P=0.149), or age (<=50 years: 13.0%; 51-65 years: 11.6%; 66-80 years 13.3%; >80
years 11.1%; P=0.864). However compared with knee arthroplasty, hip arthroplasty
had a higher suspension rate (knee arthroplasry 11.1%, hip arthroplasry 16.1%,
P=0.021). CONCLUSION: It is important to educate and manage the patients before
their knee and hip arthroplasty. Through clear diagnosis, detailed medical
history analysis careful physical examination, and targeted outpatient
examinations and tests for which priority was focused on cardiovascular or other
system diseases we could minimize the occurrence of operative suspension post
hospitalization, therefore improving the efficiency of the use of medical
resources.
PMID- 28416831
TI - [Morphology character and reduction methods of sagittally unstable
intertrochanteric fractures].
AB - OBJECTIVE: To investigate the morphology character of sagittally unstable
intertrochanteric fractures and reduction methods. METHODS: A retrospective study
was used to analyze the clinical data of sagittally unstable intertrochanteric
fractures cases, which were treated with proximal femoral nail anti-rotation
(PFNA) fixation from March 2009 to June 2016. In the study, 36 cases were
followed up completely, in which 17 cases accepted open reduction, and the other
19 cases accepted minimally invasive reduction. The operation time, amount of
bleeding, the fluoroscopy times, postoperative radiographic measurements, such as
tip-apex distance (TAD) and sliding distance of the spiral screw, and hip Harris
scores were analyzed. The morphology character of the fractures was documented
and investigated. RESULTS: The average follow-up time was 15 months. The amount
of bleeding of the open reduction group was (170.5+/-19.7) mL, and the amount of
bleeding of the minimally invasive group was (54.7+/-12.5) mL. The amount of
bleeding of the minimally invasive group was significantly less than that of the
open reduction group (P<0.001). Between the two groups, there were no significant
differences in other evaluation parameter, including operation time (P=0.054),
the fluoroscopy times (P=0.053), fracture healing time (P=0.305), postoperative
radiographic measurements, such as TAD (P=0.317) and sliding distance of the
spiral screw (P=0.206), and hip Harris scores (P=0.459). In regard to morphology
character of the fractures, the proximal anterior unstable fractures with
separation displacement were more common than the proximal posterior unstable
fractures with impaction. The characteristic feature of the proximal anterior
unstable fractures was the proximal anterior and medial long oblique fracture,
and a V shape cortical defect in the distal fracture fragment on the externally
rotation X-ray. CONCLUSION: Sagittally unstable intertrochanteric fractures can
be divided into the proximal anterior unstable fractures with separation
displacement, and the proximal posterior unstable fractures with impaction. The
two types have their own morphology character individually. The reduction should
be performed by minimally invasive techniques.
PMID- 28416832
TI - [Minimally invasive plate osteosynthesis for treatment of proximal humeral
fractures through anterolateral acromial approach].
AB - OBJECTIVE: To investigate the feasibility, surgical technique and effect of
osteosynthesis for proximal humerus fractures through the minimal incision
anterolateral acromion. METHODS: In this study, 32 patients of proximal humeral
fractures were selected and treated through the minimal incision antero-lateral
acromion between January 2012 and October 2014. Of these patients, there were 19
males and 13 females, with mean age 46 years old (range: 22-78 years). The
mechanism of injury was a trauma of simple fall for 21 patients and motor vehicle
accident for 11 patients. According to Neer classification, 18 cases had two-part
fractures, 12 had three-part fractures, and 2 had four-part fractures. All
patients were sustained operation of open reduction and internal fixation. The
average delay between trauma and surgery was 4 d (0.5-10.0 d). The operations
were performed in invariable operating room with general anesthesia. The
fractures were reduced and immobilized with anatomical locking plate through the
minimal incision anterolateral acromion during operation. Patients were received
passive motion after operation. RESULTS: All the 32 cases were followed up
ranging from 3 to 34 months with an average of 11 months. All the fractures were
healed. There was neither failure of internal fixation nor incision infection
case. The functional results of the shoulder, according to Constant-Murley score
was on an average 86 (range: 69-100). CONCLUSION: The treatment for proximal
humeral fractures through the minimal incision anterolateral acromion approach is
a feasible and effective method, which shows good results for treating proximal
humerus fractures with correct indication. There are several advantages compared
with conventional deltopectoral approach. They are minimal soft tissue
disruption, minimal blood loss and easily to manipulate technique. But it
required selection of indication strictly and surgeon's experience.
PMID- 28416833
TI - [Diagnosis and treatment for the basicervical fractures of the trochanteric
region].
AB - OBJECTIVE: To evaluate the rate of basicervical fractures and document their
diagnosis and treatment. METHODS: From January 2005 to May 2016, 28 basicervical
fractures of the 832 trochanteric fractures were collected and evaluated. The
patients were treated with multiple screws, dynamic hip screw (DHS),
intramedullary nail. Via the operation time, postoperative hospitalization, loss
of blood duration the operation, hidden blood loss, total blood loss, mean union
time and the final follow-up Harris hip score, the characteristics of different
internal fixations were compared and analyzed. RESULTS: The incidence of
basicervical fractures was 3.37% (28/832) in our study. In the intramedullary
nail group (16 patients), the operation time was 55 (20,120) min, the
postoperative hospitalization was 3(2, 7) d, the intraoperative blood loss was 50
(5,100) mL, the hidden blood loss was 533.37 (376.19, 987.15) mL, and the total
blood loss 627.35 (406.19, 1037.16) mL. The union time and final follow-up Harris
score were 6 (3, 9) months and 90.25 (74,100) min. In the DHS group (8 patients),
the operation time was 87.5 (65,115) min, the postoperative hospitalization was
5.5 (2, 17) d, the intraoperative blood loss was 100 (50,300) mL, the hidden
blood loss was 278.11 (202.43, 849.97) mL, and the total blood loss 580.19
(368.55, 899.97) mL . The union time and final follow-up Harris score were 5.5
(4, 12) months and 85.5 (84, 87) min. In the multiple screws group (4 patients),
the operation time was 47.5 (35, 75) min, the postoperative hospitalization was 5
(2, 12) d, the intraoperative blood loss was 20 (2, 70) mL, the hidden blood loss
was 150 (100.00, 412.01) mL, and the total blood loss 195.00 (120.00, 414.01) mL.
The union time and final follow-up Harris score were 4 (4, 6) months and 80 (61,
97) min. The patients treated with multiple screws and intramedullary nail had a
shorter operation time than the DNS group, but no obvious difference was found
between the other two groups (P=0.367). Postoperative hospitalization had no
significant difference among the three groups. The intraoperative bleeding was
more in the DHS group, the other two groups had no significant difference
(P=0.100). However, the hidden blood loss was more in the intramedullary nail
group, the other two groups had no significant difference (P=0.134). The total
blood loss in the intramedullary nail group was more than multiple screw group,
similar to the DHS group (P=0.483). One patient treated with multiple screws
underwent internal fixation failure three months after operation. The mean union
time and final follow-up Harris scores had no significant difference among the
three groups (P>0.05). CONCLUSION: Through this study, we found that the
incidence of basicervical fractures is low. Fractures with no shift can be
confirmed by preoperative X-ray. For displaced fractures, preoperative CT+3D
reconstruction is recommended. Surgical treatment by closed reduction and
internal fixation with DHS or intramedullary nail is shown to be very effective.
PMID- 28416834
TI - [Efficacy of transforaminal endoscopic nerve root decompression in the treatment
of degenerative lumbar spinal stenosis].
AB - OBJECTIVE: To evaluate the feasibility of transforaminal endoscopic nerve root
decompression for degenerative lumbar spinal stenosis (DLSS). METHODS: From July
2011 to April 2016, 96 cases of single segment DLSS were involved. All the
patients had unilateral lower extremity neurological symptoms, signs, neurogenic
intermittent claudication of less than 500 m. Imaging examinations (CT or MRI) or
diagnostic nerve root block confirmed single segment degeneration. The mean age
was (71.6+/-5.4) years, male: 55 cases, female: 41 cases. Their intraoperative
blood loss, operation time, complications, ambulation time and discharge time
were recorded. Leg pain VAS, ODI were used to evaluate the pain and lumbar
function of the patients. The clinical efficacy was evaluated by Nakai
evaluation. RESULTS: All the patients were performed endoscopic decompression of
the lateral recess and nerve root by removing the ventral part of the superior
facet joint, the ligamentum flavum and the intervertebral disc. The decompression
range was from the inferior edge of the upper pedicle to the superior edge of the
lower pedicle. The nerve root was detected to have no compression and the pulse
of nerve root returned to normal. The patient got ambulant on the operation day
and discharged if he had no discomfort symptom. In the study, 68 cases got follow
up. The mean follow-up time was 12.1 months (6-63 months). The VAS at different
follow-up time points was improved relative to the baseline, and the difference
was statistically significant (F=491.60, P<0.001). The ODI at different follow-up
time points was improved relative to the baseline, and the difference was
statistically significant (F=189.91, P<0.001). The excellent and good rates of
Nakai evaluation were 79.4% (excellent in 42 cases, good in 12 cases, fair in 10
cases and poor in 4 cases). The mean intraoperative blood loss was (49.29+/
11.86) mL. The mean operation time was (92.46+/-21.34) min. The mean ambulation
time was 1.8 h. The mean discharge time was 2.3 days. Postoperative epidural
hematoma was found in 1 case. Foot drop was found in 1 case. Second stage open
surgery was performed in 6 cases. CONCLUSION: We can apply transforaminal
endoscopic decompression for the patients of lumbar spinal stenosis who have
unilateral nerve root irritation. Patients with transforaminal endoscopic
decompression can get less surgical trauma, quick recovery and obtain good short
term outcome.
PMID- 28416835
TI - [Polymethylmethacrylate augmentation of bone cement injectable cannulated pedicle
screws was used to treat degenerative lumbar scoliosis with osteoporosis].
AB - OBJECTIVE: To describe the application of polymethylmethacrylate (PMMA)
augmentation of cement-injectable cannulated pedicle screws for the treatment of
degenerative lumbar scoliosis with osteoporosis. METHODS: Retrospective cohort
study was used to compare cement injectable cannulated pedicle screws (CICPs)
group with PMMA augmentation and control group with traditional method in the
correction surgery for Lenke-silva level III and level IV degenerative scoliosis
cases with osteoporosis. Both groups were followed up for 1 year. The clinical
results were assessed by visual analog scale (VAS) of pain on lumbar and lower
limbers, Oswestry disability index (ODI) score and EuroQol-5 dimensions (EQ-5D)
score. The coronal major curve Cobb angel in coronal plane and thoracic kyphosis
Cobb angle, lumbar lordosis Cobb angle and sagittal vertical axis (SVA) in
sagittal plane were tested in whole long spine X ray. The fusion rates were
evaluated by lumbar X ray and dynamic X ray. RESULTS: In this study 34 cases were
enrolled, 15 cases in CICPs group and 19 cases in control group. The general
characteristics including age, gender, weight, height, BMI and BMD were without
statistical difference between the two groups. There were (5.7+/-2.2)PMMA
augmentation screws in CICPs group. The operation time, blood loss and blood
transfusion were higher in CICPs group than in control group, but without
statistical difference. Lumbar VAS, lower limbers VAS, ODI score and EQ-5D were
all better in 1 month postoperation, 6 months postoperation and 1 year
postoperation than in preoperation in both groups. lumbar VAS scores of CICPs
group in 6 months postoperation (CICPs group 3.1+/-1.3 vs. control group 4.4+/
1.4, P<0.01) together with lumbar VAS scores (CICPs group 3.3+/-1.0 vs. control
group 5.2+/-1.4, P<0.01), ODI scores (CICPs group 22.7+/-17.2 vs. control group
31.4+/-18.5, P<0.01) and EQ-5D in 1 year postoperation (CICPs group 2.9+/-2.0 vs.
control group 3.5+/-2.5, P<0.01)were lower than those of control group. The
coronal major curve Cobb angels were all lower in 1 month postoperation, 6 months
postoperation and 1 year postoperation than in preoperation in both groups;
thoracic kyphosis Cobb angle and lumbar lordosis Cobb angle were all higher in 1
month postoperation, 6 months postoperation and 1 year postoperation than in
preoperation in both groups. The coronal major curve Cobb angel was lower in
CICPs group than that in control group in 1 year postoperation (CICPs group 17.6
degrees +/-6.9 degrees vs. control group 21.2 degrees +/-7.2 degrees ,
P<0.01)and thoracic kyphosis Cobb angle was higher in CICPs group than that in
control group in 6 months postoperation (CICPs group -33.5 degrees +/-8.8
degrees vs. control group -28.9 degrees +/-8.3 degrees , P<0.01) and 1 year
postoperation (CICPs group -33.0 degrees +/-8.1 degrees vs. control group -26.3
degrees +/-7.4 degrees , P<0.01) together with lumbar lordosis Cobb angle were
higher in CICPs group than that in control group in 1 year postoperation (CICPs
group 26.4 degrees +/-8.1 degrees vs. control group 22.1 degrees +/-7.3 degrees
, P<0.01). CONCLUSION: Polymethylmethacrylate augmentation of bone cement
injectable cannulated pedicle screws for the treatment of degenerative lumbar
scoliosis with osteoporosis was effective and safe, the short-term clinical
result was good.
PMID- 28416836
TI - [Comparison between flexible laryngeal mask airway and reinforced tracheal tube
used for lumbar vertebral surgery in prone position].
AB - OBJECTIVE: To estimate the safety and feasibility of flexible laryngeal mask
airway (FLMA) for lumbar vertebral surgery in prone position. METHODS: In the
study, 120 adult patients scheduled for lumbar vertebral surgery under
intravenous general anesthesia were divided into group FLMA and reinforced
tracheal tube (RTT) group at random. Heart rate (HR), systolic blood pressure
(SBP) and diastolic blood pressure (DBP) were recorded at the beginning of
anesthesia induction (T0) and on the time of artificial airway intubation (T1), 1
min after intubation (T2), extubation (T3), 1 min after extubation (T4) as well.
The number and time required for intubation were recorded. Peak airway pressure
(PPEAK), airway sealing pressure (PAS) in group FLMA and fiberoptic bronchoscopy
scale (FBS) were recorded after artificial airway intubation, turned over into
prone position and after the operation started, as well as on the time of 1 hour
after the operation started, 2 hours after operation started and when the
operation stopped. Finally, respiratory complications after extubation, including
hypoxemia, laryngospasm, coughing, vomiting, hoarseness, and pharyngalgia, were
observed and whether there was blood or sewage inside and outside the artificial
airway was recorded. RESULTS: There was no difference in the number and time
required for intubation between the two groups (P>0.05). There was no difference
in PPEAK and FBS between the two groups, and also the same at the different time
points in each group (P>0.05). PAS in group FLMA was the same at the diverse time
points during anesthesia (P>0.05) and always higher than PPEAK in the
perioperative period. In group FLMA, there was no difference in HR, SBP and DBP
between the time points of T2 and T1, also of T4 and T3 (P>0.05). In group RTT,
HR, SBP and DBP were significantly higher between the time points of T2 and T1
(P<0.01); SBP was significantly higher between the time points of T4 and T3
(P<0.01), DBP and HR were higher between the time points of T4 and T3 (P<0.05).
SBP in group FLMA was significantly lower than in group RTT at T2 (P<0.01), HR
and DBP were lower than those in group RTT simultaneously (P<0.05). On the time
point of T4, SBP, DBP and HR in group FLMA were lower than those in group RTT
(P<0.05). The incidence of coughing and pharyngalgia after extubation was
significantly lower in group FLMA than in group RTT (P<0.01), with the incidence
of hoarseness was lower in group FLMA than in group RTT (P<0.05). There was no
difference in the incidence of hypoxemia, vomiting and blood seen outside the
cuff between the two groups (P>0.05) while no laryngospasm and sewage seen
outside the artificial airway in each group. CONCLUSION: For suitable patients,
FLMA can be used in mechanical ventilation forlumbar vertebral surgery in prone
position with more stable circulation and less respiratory complications than
RTT. Further clinical validation is needed for the safety of FLMA.
PMID- 28416837
TI - [Clinical comparison of polymethylmethacrylate and bone cement in the treatment
of osteoporotic vertebral compression fractures: a retrospective study].
AB - OBJECTIVE: To analyze the outcomes of patients with osteoporotic vertebral
compression fractures treated with polymethylmethacrylate (PMMA) and GeneX bone
cement in percutaneous kyphoplasty and to provide guidance in selecting the
vertebral filling material for this procedure. METHODS: In this study, 86
patients with osteoporotic vertebral compression fractures treated at Peking
University Third Hospital between June 2012 and June 2013 were retrospectively
analyzed. The patients were followed-up with questionnaires and X-ray and CT
examinations after 1 month, 3 months, 6 months, and 1 year. Postoperative
conditions, including recovery rate of vertebral height, recovery rate of
vertebral Cobb angle, CT data, reductions in visual analogue scale (VAS) and
Oswestry scores, and postoperative complications, were evaluated. The results
were analyzed using SPSS 18.0. RESULTS: According to the rank sum test, there
were significant differences in the recovery rate of vertebral height, vertebral
Cobb angle and vertebral volume between the two groups after 3 months, 6 months,
and 1 year (P<0.05). The GeneX group had greater losses in vertebral height, Cobb
angle and volume than did the PMMA group. The PMMA group had 3 cases of cement
leakage and 1 case of an adjacent vertebral fracture after percutaneous
kyphoplasty. The GeneX group had 2 cases of cement leakage. CONCLUSION: GeneX
bone cement is similar to PMMA in terms of postoperative pain relief. As the
filling material in percutaneous kyphoplasty, it is effective at maintaining
vertebral height, quickly improves strength and stiffness of the vertebral body
and has fewer complications. However, it is not satisfactory in maintaining long
term postoperative vertebral height. GeneX bone cement can be used as the filling
material for patients with osteoporotic vertebral compression fractures in
percutaneous kyphoplasty. Patients with severe osteoporosis and vertebral
compression should be treated with standardized osteoporosis treatment and should
try to avoid early postoperative walking exercises. Sustained vertebral filling
materials, such as PMMA, are more suitable for such patients. Research into
better biodegradable materials is still needed.
PMID- 28416838
TI - [Clinical research on robot-assisted percutaneous pelvic and acetabular screws
surgery].
AB - OBJECTIVE: To evaluate the security and efficiency of a surgical robotic assisted
percutaneous screw fixation for the treatment of pelvic and acetabular fractures.
METHODS: In the study, 12 patients with pelvic and acetabular fractures who were
treated in Beijing Jishuitan Hospital from January to April in 2016 were involved
in this research. The research subjects were randomly divided into two groups:
the experimental group and the control group. Robotic-assisted percutaneous
sacroiliac screw internal fixations were performed under the guidance of
fluoroscopy navigation in the experimental group; in the control group, doctors
operated manually guided by fluoroscopy. Statistical analysis was performed on
the total operation time, the intraoperative fluoroscopy time, the adjustment
numbers of intraoperative guide wires, the excellent rate of screw placement and
the incidence of adverse events in order to evaluate the security and efficiency
of a surgical robotic assisted percutaneous screw fixation for the treatment of
pelvic and acetabular fractures. RESULTS: Eleven screws were placed in 7 patients
from the experimental group, while 7 screws were placed in 5 patients from the
control group in total. All the screw placement positions were satisfactory
according to postoperative CT images. The excellent rates of screw placement
position were 100% in both groups. However, the P value was 0.016 based on the
comparison between the screws' distribution in the two groups which meant that
the screw distribution of the experimental group was better than that of the
control group. The average fluoroscopy time needed for screw insertion was
(7.36+/-2.63) s in the experimental group while (41.80+/-13.99) s in the control
group (P<0.001). This suggested that the difference between the two groups had
statistical significances. Intra-operative fluoroscopy time of the experimental
group was significantly smaller than that of the control group. The number of the
average screw adjustment was (0.36+/-0.48) times in the experimental group while
(9.00+/-3.06) times in the control group (P=0.003). This suggested that the
difference of the number of the guide needle adjustment between the two groups
had statistical significances, and the number of the experimental group was
smaller than that of the control group. The average operation time was (43.86+/
49.06) min in the experimental group while only (29.00+/-12.14) min were needed
in the control group (P=0.528). This suggested that the difference between the
two groups had no statistical significance. That is, the total operation time of
the two groups was equal. All the screws were in satisfactory positions according
to validation results of CT scans. No complications such as screw breaking out
the bone cortex and entering into the knee joint cavity, wound infection
occurred. CONCLUSION: Surgical robots are suitable for robot-assisted
percutaneous screw fixation in pelvic and acetabular fractures. Robot-assisted
treatment of pelvic and acetabular fractures has significant advantages over
manual operations including high accuracy, small perspective radiation, safety
and efficiency.
PMID- 28416839
TI - [A correlation analysis of the ankle CT and ankle fracture classification].
AB - OBJECTIVE: To summarize the CT features of ankle fracture and to analyze the
relationship between the CT images and the most commonly used ankle fracture
classification. METHODS: With 369 cases of adult ankle fractures analyzed
retrospectively, the CT images 1 cm above the ankle joint and its
characteristics, the Danis-Weber classification of ankle fracture were studied,
and so was the relationship between CT images and the fracture classification.
RESULTS: There were 8 forms of CT images. With a, b, and c referred to the
fibular fracture, posterior malleolar fracture and interosseous tibiofibular
ligament (IOL) rupture respectively. 369 CT imges had 40 cases of 0 degree injury
(fibula, posterior malleolus, IOL all intact); 60 cases of Ia degree injury
(fibular fracture, posterior malleolus and IOL intact), 3 cases of Ib degree
injury (fibula intact, posterior malleolus fracture, IOL intact), 26 cases of Ic
degree injury (fibula and posterior malleolus intact, IOL rupture); 163 cases of
IIab degree injury (fibula and posterior malleolus fractures, IOL intact), 6
cases of IIac degree injury (fibular fracture, posterior malleolus intact, IOL
rupture), 61 cases of IIbc degree injury (fibula intact, posterior malleollar
fracture, IOL rupture); 10 cases of III degree injury (fibular fracture,
posterior malleollar fracture and IOL rupture). According to the Danis-Weber
classification, there were 18 cases of type A, 238 cases of type B, 94 cases of
type C, and 19 cases without fibular fracture. The prevalence of IOL rupture were
0, 5.9%, and 88.3% in types A, B, and C respectively. There was a correlation
between the CT image and Danis-Weber classification, the incidence of IOL rupture
was changed with the severity of Danis-Weber classification, and the difference
was statistically significant after the rank correlation test (Spearman R=0.781,
P<0.001). IOL rupture not determined by the fracture classification was found
with the CT images and the incidence was 5.9%. CONCLUSION: Cross-sectional CT
images 1 cm above the ankle joint can clearly determine the IOL injury
preoperatively with a good correlation with the Danis-Weber fracture
classification, IOL rupture unrecognized with the fracture classification can
also be noticed with the CT image.
PMID- 28416840
TI - [B7-H3 silencing inhibits human hematological malignancy xenograft tumor
tumorigenesis and metastasis in nude mice].
AB - OBJECTIVE: To investigate the effect and mechanism of targeted B7-H3 gene
silencing on the tumorigenesis and metastasis of human hematological malignancy
xenograft tumor in nude mice. METHODS: Real-time fluorogentic quantitative PCR
(qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13
strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which
expressed high level of B7-H3 were screened out. Targeted B7-H3 knockdown in
U937, Maver and Z138 was performed by lentivirus transduction and the effect of
B7-H3 silencing in stable cell lines was tested by qPCR and FCM. Injecting the
nine groups subcutaneously into the nude mice to establish xenograft models after
dividing the U937, Maver and Z138 into non-infected control group (CON), B7-H3
knockdown group (KD) and negative non-targeted control infected group
(NC),respectively, for detecting the tumorigenicity and metastasis in vivo.
Furthermore, the expression of Ki-67 in xenograft tumors was detected by
immunohistochemistry (IHC). The expression of metalloproteinase 2 (MMP-2) was
detected by western blot. RESULTS: The stable B7-H3 silencing cell lines of U937,
Maver and Z138 were successfully established. Compared with the NC group, the KD
groups of U937, Maver and Z138 had an obviously slower tumor growth. The average
tumor inhibition rates at the end of observation period were 61.83% (F=43.78,
P<0.05), 59.12% (F=36.51, P<0.05) and 67.37% (F=40.29, P<0.05); there was no
significant difference in tumor volume growth between the NC group and the CON
group (P>0.05). The liver distant metastasis of all the xenograft tumor models in
nude mice was the most common and the rates of distant metastasis in KD groups
were significantly lower than that of the corresponding NC groups. The Ki-67
indexes of the KD groups were significantly lower than those of the relative NC
groups in three cell lines (U937: 40.3%+/-5.2% vs. 79.1%+/-6.3%, q=30.31, P<0.05,
Maver: 35.2%+/-6.4% vs. 69.6%+/-5.1%, q=24.82, P<0.05; Z138: 38.4%+/-7.1% vs.
75.7%+/-4.8%, q=28.07, P<0.05); there was no significant difference in the
expression of Ki-67 between the NC group and the CON group (P>0.05). The
expressions of MMP-2 were also significantly lower in the KD groups than in the
NC groups (U937: q=14.59, P<0.05; Maver: q=9.25, P<0.05; Z138: q=11.04, P<0.05);
there was no significant difference in the expression of MMP-2 between the NC
group and the CON group (P>0.05). CONCLUSION: Targeted B7-H3 gene silencing could
inhibit the tumorigenesis and metastasis of human hematological malignancy
xenograft tumor in nude mice. The mechanism may be related to the down-regulation
of Ki-67 and MMP-2.
PMID- 28416841
TI - [Urothelial carcinoma-associated 1 enhances tamoxifen resistance in breast cancer
cells through competitively inhibiting miR-18a].
AB - OBJECTIVE: To investigate how urothelial carcinoma-associated 1 (UCA1) and miR
18a modulates acquired tamoxifen resistance and the relevant mechanisms in
estrogen receptor (ER) positive cancer cells. METHODS: qRT-PCR was performed to
detect UCA1 and miR-18a expression in breast cancer cells. Dual luciferase assay
was performed to detect the binding between miR-18a and UCA1 3'UTR. Tamoxifen
sensitive MCF-7 cells were transfected with UCA1 expression vector or miR-18a
inhibitors. Tamoxifen resistant LCC9 and BT474 cells were transfected with UCA1
siRNA or miR-18a mimics. CCK-8 assay was performed to detect cell viability. Soft
agar assay was performed to assess cell colony formation. Flow cytometric
analysis was performed to check cell cycle distribution. RESULTS: UCA1 was
significantly upregulated in tamoxifen resistant LCC2, LCC9, and BT474 cells than
in tamoxifen sensitive MCF-7 cells. UCA1 expression was significantly upregulated
in MCF-7 cells after treatment with 0.1 MUmol/L tamoxifen. UCA1 overexpression
enhanced cell viability of MCF-7 cells after tamoxifen treatment, while UCA1
siRNA significantly suppressed viability of LCC9 and BT474 cells after tamoxifen
treatment. In MCF-7 cells, compared with vector control+tamoxifen group, the
average cell colony number and colony size of the UCA1+tamoxifen group was 19.0%
more and 29.0% larger respectively, while the proportions of the cells in G1
phase and in S phase were 7.3% lower and 6.7% higher respectively. In BT474
cells, compared with siRNA control+tamoxifen group, the average cell colony
number and colony size of the si-UCA1+tamoxifen group were 54.0% less and 42.0%
smaller respectively, while the proportions of the cells in G1 phase and in S
phase were 9.0% higher and 6.2% lower respectively. UCA1 directly interacted with
miR-18a and reduced its expression in ER positive breast cancer cells. Knockdown
of miR-18a increased viability of MCF-7 cells after tamoxifen treatment, while
miR-18a overexpression significantly reduced viability of BT474 cells after
tamoxifen treatment. In MCF-7 cells, compared with miRNA inhibitor
control+tamoxifen group, the average cell colony number and colony size of the
miR-18a inhibitor+tamoxifen group were 15.0% more and 33.0% larger respectively,
while the proportions of the cells in G1 phase and in S phase were 8.8% lower and
5.3% higher respectively. In BT474 cells, compared with miRNA control+tamoxifen
group, the average cell colony number and colony size of the miR-18a
mimics+tamoxifen group were 47.0% less and 25.0% smaller respectively, while the
proportions of the cells in G1 phase and in S phase were 13.3% higher and 7.9%
lower respectively. CONCLUSION: UCA1 can increase tamoxifen resistance of ER
positive breast cancer cells via competitively inhibiting of miR-18a.
PMID- 28416842
TI - [Drainage characteristic of the brain interstitial fluid detected by using
fluorescence and magnetic tracer method].
AB - OBJECTIVE: Compare the results of molecular diffusion and mass flow in the
interstitial space(ISS) displayed by using optical and magnetic probes and study
partitioned drainage of the brain interstitial fluid (ISF). METHODS: In the
study, 36 male SD rats were randomly divided into fluorescent inspection group
(18), magnetic tracer group (18). Then they were divided equally into caudate
nucleus (Cn), thalamus (T) and substantia nigra (Sn) subgroup, 6 rats in each
subgroup. Referencing the brain stereotaxic atlas, the coronal globus pallidus as
center level, Cn, T or Sn were acted as puncture positioning target. A 10 MUL
microsyringe was stereotaxically positioned and the lucifer yellow (LY) solution
of 2 MUL 10 mmol/L was infused into centric position. The coronary slices undergo
cardiac perfusion and fix respectively in time point Cn 3 h, T 2 h and Sn 1 h.
The rat brain was placed in rat stainless steel brain matrices and cut backward
along visual intersection. The injection point of coronal slice as the center
level, take 3 slices in front of the center level and 2 slices behind of it. 1 mm
for each slice and 6 slices in total. Then slices were detected by laser scanning
confocal microscope (LSCM). Simultaneous, in the same coordinate brain regions of
another three groups, a gadolinium-diethylene triamine pentaacetic acidm (Gd
DTPA) solution of 2 MUL 10 mmol/L was infused into different injection and
detected by MRI tracer-based method. Then the Radiant can be used to measure
distribution area of Gd-DTPA. RESULTS: LY and Gd-DTPA have different distribution
regions in Cn, T and Sn. After LY and Gd-DTPA were introduced into the Cn
subgroup 3 h, compare the 1 to 6 levels distribution area of LY and Gd-DTPA as
follows: (10.95+/-4.27) mm2 vs. (8.33+/-2.25) mm2, (18.16+/-4.74) mm2 vs.
(16.42+/-2.88) mm2, (24.57+/-3.65) mm2 vs. (20.75+/-2.29) mm2, (34.81+/-3.32) mm2
vs. (28.88+/-1.51) mm2, (30.53+/-3.12) mm2 vs. (20.92+/-2.75) mm2, (12.15+/-4.92)
mm2 vs. (10.00+/-1.89) mm2. The statistical analysis of every level was made by T
test, and the difference of the distribution area between the two tracers were
not statistically significant (t=0.940, P=0.400; t=0.546, P=0.614; t=1.534,
P=0.200; t=2.809, P=0.480; t=2.693, P=0.055; t=0.707, P=0.518); After LY and Gd
DTPA were introduced into the T subgroup 2 h, compare the 1-6 levels distribution
area of LY and Gd-DTPA as follows: (5.56+/-4.61) mm2 vs. (3.33+/-2.25) mm2,
(16.21+/-3.36) mm2 vs. (11.42+/-2.88) mm2, (19.00+/-5.21) mm2 vs. (15.75+/-2.29)
mm2, (25.32+/-5.49) mm2 vs. (22.33+/-3.25) mm2, (17.34+/-5.31) mm2 vs. (15.92+/
2.75) mm2, (7.67+/-6.19) mm2 vs. (5.00+/-1.89) mm2. The statistical analysis of
every level was made by T test, and the difference of the distribution area
between the two tracers were not statistically significant (t=0.753, P=0.493;
t=1.875, P=0.134; t=0.990, P=0.378; t=0.810, P=0.464; t=0.413, P=0.701; t=0.716,
P=0.514); After LY and Gd-DTPA were introduced into the Sn subgroup 1 h, compare
the 1-6 levels distribution area of LY and Gd-DTPA as follows: (6.78+/-4.56) mm2
vs. (4.75+/-2.00) mm2, (12.65+/-5.04) mm2 vs. (10.44+/-1.13) mm2, (19.51+/-6.54)
mm2 vs. (17.55+/-0.30) mm2, (28.72+/-5.45) mm2 vs. (24.48+/-1.32) mm2, (21.34+/
4.42) mm2 vs. (17.72+/-0.25) mm2, (13.00+/-5.46) mm2 vs. (12.00+/-2.88) mm2. The
statistical analysis of every level was made by T test and the difference of the
distribution area between the two tracers were not statistically significant
(t=0.705, P=0.519; t=0.743, P=0.499; t=0.517, P=0.656; t=1.310, P=0.260; t=1.416,
P=0.292; t=0.281, P=0.793), but the distribution area of LY is slightly more than
Gd-DTPA. CONCLUSION: LSCM imaging technology confirmed partitioned drainage of
the brain ISF found by MRI tracer-based method and provided technology and method
validation for MRI tracer-based method. LSCM imaging technology with higher
contrast and resolution, therefore more sophisticated partitioned drainage of the
brain interstitial fluid were got.
PMID- 28416843
TI - [Influences of repeated propofol anesthesia on hippocampal apoptosis and long
term learning and memory abilities of neonatal rats].
AB - OBJECTIVE: To investigate the influences of repeated propofol anesthesia on the
hippocampal apoptosis and the long-term learning and memory abilities of neonatal
rats. METHODS: In the study, 45 male Sprague-Dawley rats, aged 7 days, were
randomly divided into 3 group (n=15 each): control group (C group) that received
intralipid 7.5 mL/kg intraperitioneal (IP) once a day*7 days; group propofol 1
(P1) that received propofol 75 mg/kg IP once a day*7 days; group propofol 2 (P2)
that received intralipid 7.5 mL/kg IP once a day*6 days+propofol 75 mg/kg IP on
the 7th day. In each group, 5 animals were chosen and arterial blood samples were
obtained immediately after the animals were fully awake for blood gas analysis.
Learning and memory abilities were assessed using Morris water maze when the
other rats were 4 weeks old. The animals were decapitated after the tests. The
hippocampi were isolated for detection of neuron-specific nucleoprotein (NeuN)
expression by immunohistochemistry method and the expression of caspase-3 using
the Western blot. RESULTS: There was no significant difference in the indexes of
blood gas analysis among the 3 groups. Morris water maze test: compared with
group C, the escape latency and the length of searching on the 5th day were
significantly prolonged, and the searching time in target quadrant and platform
crossing on the 6th day were significantly decreased in group P1 (P<0.05) but not
in group P2. Compared with group C, NeuN-positive neurons were decreased, and the
expression of caspase-3 was increased in the rats of group P1 (P<0.05) but not in
group P2. CONCLUSION: Repeated propofol anesthesia may destroy long-term learning
and memory abilities by inducing apoptosis of hippocampal neurons in neonatal
rats, while single dose of propofol has no obvious effect on the hippocampal
apoptosis and long-term learning and memory of neonatal rats.
PMID- 28416844
TI - Clinical characteristics of neurogenic dysphagia in adult patients with Chiari
malformation type I.
AB - OBJECTIVE: To investigate changes of swallowing function and associated symptoms
in Chiari malformation typeI (CMI) patients with and without dysphagia by the
analysis of their clinical and high-resolution manometry (HRM) parameters.
METHODS: A total of 42 patients diagnosed with symptomatic CMI without
atlantoaxial dislocations which were confirmed by clinical manifestations and
magnetic resonance imaging (MRI) findings between January 2010 and July 2015 at
Peking University Third Hospital were included in this study. Twenty patients had
a history of various dysphagia symptoms, or reported symptoms of choking,
coughing after eating or drinking, while the other 22 patients denied symptoms of
dysphagia. The data collected from the medical records of these patients included
the patient's age, sex, date of diagnosis, duration of illness, symptoms, results
of MRI and HRM, and date of surgery. RESULTS: (1) Dysphagia group had 14 female
patients, and no-dysphagia group had 8 female patients. Dysphagia usually
occurred in female patients, and in addition to dysphagia, we recorded other
symptoms and signs in the CMI patients, including numbness, hypoesthesia, limb
weakness, neck pain, muscle atrophy, ataxia, hoarseness, symptoms caused by
posterior cranial nerve damage, pharyngeal reflex, uvula deviation, and pyramidal
signs. A higher percentage of the CMI patients with dysphagia (15/20) had
symptoms of posterior cranial nerve damage compared with the control group (5/22;
P=0.01). (2)HRM showed a significant difference in upper esophageal sphincter
(UES) relax ratio measurement (75.3% vs. 63.1%, P=0.023) and UES proximal margin
(17.2 cm vs. 15.7 cm, P=0.005) between the two groups. (3) The percentage of
syringomyelia affecting the bulbar or upper cervical region on MRI was
significantly higher in the dysphagia group (17/20 vs. 7/22, P=0.001).
CONCLUSION: CMI was usually accompanied by symptoms caused by posterior cranial
nerve damage, ataxia, and positive pyramidal signs. Location of the syringomyelia
affecting specifically the bulbar or upper cervical region was associated with
dysphagia in CMI patients. These findings suggest that the mechanism of dysphagia
in CMI may be due to a dysfunction in the neurological pathway of pharyngeal
muscle movement. Dysphagia etiology work-up should include CMI in the
differential diagnosis.
PMID- 28416845
TI - [Anesthetic choice for patients undergoing cesarean section complicated with
placenta implantation].
AB - OBJECTIVE: To investigate the anesthetic choice for patients undergoing cesarean
section complicated with placenta implantation. METHODS: A retrospective case
review of the patients with placenta implantation between 2008 and 2013 at Peking
University Third Hospital was conducted in the International Classification of
Diseases (ICD)-9 codes, excluding natural birth and not first diagnosed in our
hospital, a total of 96 cases were incorporated into this study. According to the
degree of implantation, they were divided into three groups: accreta group,
increta group and percreta group. We analyzed the time from the start of surgery
to baby delivery and the anesthetic technique. RESULTS: The accreta group
included 49 cases, the increta group 33 cases, and the percreta group 14 cases.
The average time from the start of surgery to fetus delivery in the three groups
were (6.7+/-3.0) min, (7.2+/-4.6) min, and (11.9+/-4.9) min, and the percreta
group was significantly different from the accreta group and the increta group
(P<0.05). There were significant differences among the three groups in anesthetic
choices (P<0.001): in the accreta group, 45 cases (91.8%) underwent spinal
anesthesia, 2 cases (4.1%) underwent general anesthesia, and 2 cases (4.1%) were
converted to general anesthesia after spinal anesthesia during the operation; in
the increta group, 22 cases (66.7%) underwent spinal anesthesia, 4 cases (12.1%)
underwent general anesthesia, and 7 cases(21.2%) were converted to general
anesthesia after spinal anesthesia; in the percreta group, 2 cases (14.3%)
underwent spinal anesthesia, 2 cases (14.3%) underwent general anesthesia, and 10
cases (71.4%) were converted to general anesthesia after spinal anesthesia.
CONCLUSION: Spinal anesthesia can be used as the first choice of cesarean section
complicated with placenta implantation and general anesthesia should be
considered in placenta percreta.
PMID- 28416846
TI - [Influence of the Arg-Gly-Asp-Ser sequence on the biological effects of bioactive
glass on human dental pulp cells].
AB - OBJECTIVE: Positive effects of bioactive glass (BG) on proliferation,
mineralization, and differentiation of human dental pulp cells (hDPCs) was
already verified in various former studies. The Arg-Gly-Asp-Ser sequence (RGDS)
was confirmed of affecting cell adhesion. Before further investigation, the
objective of this study is to investigate whether RGDS can affect the effects of
BG on the adhesion, proliferation and mineralization of hDPCs. METHODS: hDPCs
were harvested from third molars of 18-25-year-old individuals after informed
consent. Enzyme digestion technique was used. The 4th to 6th generation of hDPCs
were used for all experiments. The cells of the experimental groups were cultured
in Dulbecco minimum essential medium (DMEM) containing ionic dissolution products
of BG and RGDS of several concentrations (12.5 mg/L, 25.0 mg/L, 50.0 mg/L, 100.0
mg/L, 200.0 mg/L). DMEM containing ionic dissolution products of BG without RGDS
was used for cell culture as control group. Cell adhesion was tested 4 h after
cell seeding by MTT assay. Cell proliferation was examined at 1, 3, 5, 7, and 9 d
after cell seeding by MTT assay. Cell mineralization was investigated on days 14
and 28 by alizarin red staining. After being stained and dried, mineralized
nodules were dissolved by cetylpyridinium chloride (CPC) for semi-quantitative
test. Results were statistically analyzed by one way ANOVA, SPSS (version 19.0)
and P<0.05 was considered to be significant. RESULTS: Cell adhesion in BG group
showed no difference from that in DMEM group. Compared with BG group, hDPCs in
BG+RGDS groups suggested weaker cell adhesion.When the concentration of RGDS
increased, the adhered cell number decreased. hDPCs cultured with BG and RGDS
showed lower proliferation activity in the early stage, while no significant
difference was observed after 3 d. BG group promoted the mineralization of hDPCs
compared with positive control group, negative control group and RGDS group. No
significant difference was observed between BG+RGDS group and BG group or between
RGDS group and positive control group. CONCLUSION: BG promotes proliferation and
mineralization without affecting cell adhesion of hDPCs. Unbounded RGDS inhibits
cell adhesion, but has no influence on the positive effects of BG on the
proliferation and mineralization of hDPCs.
PMID- 28416847
TI - [Effects of bioactive glass and extracted dentin proteins on human dental pulp
cells].
AB - OBJECTIVE: To investigate the proliferation, odontogenic differentiation and
mineralization of human dental pulp cells (HDPCs) on bioactive glass(BG) and
extracted dentin proteins(EDP). METHODS: Primary HDPCs were isolated from third
molars by enzyme digestion and were cultured in Dulbecco's minimum essential
medium (DMEM). Then the 4th generation of HDPCs was cultured with DMEM, which
contained BG-EDP, BG, and EDP, respectively. Meanwhile HDPCs were cultured in
DMEM as control group. Proliferation of HDPCs was evaluated by 3-(4,5-dimethyl-2
thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) colorimetric assay.
Odontogenic differentiation was determined by alkaline phosphatase (ALP) activity
assay and real-time PCR. Mineralization was investigated by Alizarin red staining
and cetylpyridinium chloride (CPC) assay. RESULTS: The proliferation of HDPCs was
increased significantly in BG-EDP group on 3,7,and 9 d (optical density value:
1.36+/-0.06, 2.52+/-0.20, 2.72+/-0.29) compared with BG (optical density value:
1.20+/-0.26, 2.33+/-0.26, 2.50+/-0.30), EDP(optical density value: 1.13+/-0.15,
2.10+/-0.13, 2.38+/-0.22) and control group (optical density value: 0.84+/-0.17,
1.84+/-0.18, 1.95+/-0.19), P<0.05. After 7 days, ALP activity of BG-EDP group had
no statistical difference compared with EDP group and control group; the
expression of odontogenic differentiation genes (DSPP, DMP-1) showed no
difference among all the groups(P>0.05). After 14 days, ALP activity of BG-EDP
group (56.67+/-1.83) was significantly upregulated compared with EDP group
(41.98+/-9.71) and control group (30.82+/-6.70), P<0.05, but had no statistical
difference compared with BG group (56.29+/-6.20), P>0.05; DSPP gene expression
was upregulated significantly in BG-EDP group (5.79+/-1.94) compared with the
other groups (P<0.05); DMP-1 gene expression of BG-EDP group (3.87+/-1.87)
increased but had no statistical difference compared with the other groups
(P>0.05). The alizarin red staining showed more mineral nodules in BG-EDP group,
the cetylpyridinium chloride semi-quantification presented higher calcification
in BG-EDP group (0.27+/-0.01) compared with the other groups (P<0.05).
CONCLUSION: Compared with either BG or EDP, BG-EDP significantly promotes the
proliferation, odontogenic differentiation and mineralization of HDPCs.
PMID- 28416848
TI - [Effect of low-level laser irradiation on proliferation and osteogenic
differentiation of human adipose-derived stromal cells].
AB - OBJECTIVE: To examine the in vitro effects of low-level laser irradiation (LLLI)
on proliferation and differentiation of human adipose-derived stromal cells
(hASCs). METHODS: Cultured cells were exposed to different doses of LLLI with a
semiconductor diode laser (980 nm; 100 mW-12 W power output). The effects of
laser on proliferation were assessed daily up to seven days of culture in cells
irradiated for four consecutive days with laser doses of 2, 4, 6 or 8 J/cm2, the
cells without irradiation were used as controls. Half of the cells were changed
to osteogenic medium (OM) when they had grown to 70% confluence. The hASCs both
with and without osteogenic supplements were divided into three groups, and each
group was irradiated at doses of 0, 2 and 4 J/cm2. In order to examine the in
vitro effects of LLLI on osteogenic differentiation of hASCs, the alkaline
phosphatase activity was assessed on day 7, and alizarin red staining (AR-S) and
quantitative detection were assessed on days 14 and 21. The expression of
osteoblast master genes (ALP and Runx2) were tested on days 7 and 14. RESULTS:
The proliferation medium(PM)+LLLI4 J/cm2 group had the highest multiplication
rate. In the groups with osteogenic supplements, LLLI increased alkaline
phosphatase activity and mineralized nodule formation, and stimulated the
expression of ALP and Runx2. Furthermore, the effect became more obvious at high
dose. CONCLUSION: Our data demonstrated that hASCs proliferation and osteogenic
differentiation were enhanced by LLLI. With the increase of laser dose, the
effect of LLLI would be enhanced at first, and then be decreased after reaching a
peak.
PMID- 28416849
TI - [Effect of mechanical self-cleaning of tongue coating on malodor in halitosis
patients originating from tongue coating].
AB - OBJECTIVE: To evaluate the malodor level and to explore the effect of mechanical
self-cleaning of tongue coating in patients with halitosis originating from
tongue coating. METHODS: Ten patients with halitosis originating from tongue
coating were enrolled and divided into two groups randomly. The patients in test
group received instruction of mechanical cleaning of tongue coating while no such
instruction was given to control group. Organoleptic test (OLT) score, volatile
sulfide compounds (VSC) value, area of tongue coating (Ta), thickness of tongue
coating (Tt) and periodontal condition were recorded at baseline and were
repeated at the end of 1 week, 2 weeks, 4 weeks and 8 weeks later. The clinical
outcomes were compared at different time points between the groups. Also, changes
within the group were analyzed. RESULTS: As time went by, tongue coating area and
thickness tended to decrease in test group while the changes showed no
statistically difference (P>0.05). The organoleptic score in test group decreased
significantly (P<0.001). Changes of volatile sulfide compounds value within each
group had no statistically difference (P>0.05), though they showed a tendency to
decrease and fewer changes in control group were found. Compared with the
baseline, average probing depth and bleeding index (P<0.05) were significantly
lower in both the groups at the end of the test period, while no statistically
difference was observed between test group and control group (P>0.05). Plaque
index showed no difference at different time points in both the groups (P>0.05).
CONCLUSION: Mechanical self-cleaning of tongue coating did not influence plaque
index while it had tendency to reduce tongue coating area and thickness. Malodor
could be released after self-cleaning of tongue coating to a certain extent,
indicating necessity and importance of intervention role by dentists.
PMID- 28416850
TI - [Treatment of complicated intra-articular distal radius fractures with extended
flexor carpi radialis approach].
AB - OBJECTIVE: To discuss the effect of treatment of complicated intra-articular
distal radius fractures with extended flexor carpi radialis approach. METHODS: A
retrospective analysis of 38 cases with fresh complicated intra-articular distal
radius fractures treated by using extended flexor carpi radialis approach in our
hospital from October 2012 to March 2015, with 25 males and 13 females. The
average age was (52.76+/-8.62) years (32-64 years). The average time to surgery
was (5.42+/-1.91) d (3-10 d), with left wrist 17 cases and right wrist 21 cases.
All the patients were with C3 distal radius fractures according to Association
for the Study of Internal Fixation (AO/ASIF) classification. The follow-up was
conducted 1, 2, 3, 6, and 12 months after operation, including AP and lateral X
ray, wrist extension and flexion, radial deviation and ulnar deviation, forearm
pronation and supination, and grip strength. At the end of 6 and 12 months after
operation, all the patients were evaluated by using the modified Garland-Werley
score and patient rated wrist evaluation (PRWE). RESULTS: All the patients got
good bone union, and their follow-up time was more than 12 months. The average
follow-up time was (16.37+/-2.85) months (12-22 months). The score of modified
Garland-Werley evaluation 6 months postoperation was 5.37+/-2.82, excellent and
good rate was 84.21%, the score of modified Garland-Werley evaluation 12 months
postoperation was 5.03+/-2.60, excellent and good rate was 86.84%. The score of
PRWE 6 months postoperation was 15.82+/-8.38, the score of PRWE 12 months
postoperation was 12.17+/-7.58. CONCLUSION: The extended flexor carpi radialis
approach is effective for the treatment of complicated intra-articular distal
radius fractures and can avoid the complications of volar and dorsal combination
approach.
PMID- 28416851
TI - [One of the pitfalls in the surgical treatment of maisonneuve fractures: a case
report].
AB - There exist controversies in the surgical treatment of maisonneuve injury with
regard to reduction and fixation of syndesmosis and management of proximal
fibular fracture. It is very important for the orthopaedic surgeons to learn more
techniques and avoid pitfalls from clinical practice. We summarized the clinical
data of 1 failed case, a 20-year-old girl with big body weight who underwent a
primary surgery for the treatment of maisonneuve fracture with minimally invasive
reduction and fixation of ankle syndesmosis and posterior malleolus and open
reduction and internal fixation of medial malleolus, then a revision surgery for
the treatment of iatrogenic syndesmotic malreduction with open reduction and re
stabilization of ankle syndesmosis supplemented with open reduction and internal
fixation of proximal fibular facture. The malreduction of distal fibula was not
found until finishing the postoperative computed tomography (CT) scan 2 weeks
after the primary surgery, then the patient experienced an revision surgery
including removal of the screws installed primarily for fixation of ankle
syndesmosis, and open reduction and internal fixation of proximal fibular
fracture, and limited open reduction and re-stabilization of ankle syndesmosis.
Then the patient rehabilitated regularly under the direction of the surgeon who
performed these two operations, and the postoperative recovery was smooth, then
the hardwares for fixation of ankle syndesmosis and fracture of proximal fibula
and medial malleolus were removed at different postoperative time. The patient
experienced an excellent outcome at the end of the 3-year follow-up. The reasons
for the failure in this case might include the overemphasized minimally invasive
technique in the process of reduction, inaccurate assessment of intraoperative
fluoroscopy and postoperative radiographs, and inappropriate utilization of the
reduction clamp. Attention should be paid to the fact that an obliquely placed
clamp for closed reduction of diastasis of ankle syndesmosis could result in
syndesmotic malreduction. The worsened alignment of the fracture end of proximal
fibula observed by intraoperative fluoroscopy may alert surgeons to syndesmotic
malreduction. Partial exposure of syndesmosis and anatomical reduction and
fixation of proximal fibular fracture may be useful measurres to avoid
malreduction of ankle syndesmosis in the surgical treatment of maisonneuve injury
in some patient, especially the patient with critically destabilized ankle.
PMID- 28416852
TI - [First aid system for trauma: development and status].
AB - With the great progress of the economy, the level of industrialization has been
increasing year by year, which leads to an increase in accidental trauma
accidents. Chinese annual death of trauma is already more than 400 000, which
makes trauma the fifth most common cause of death, following malignant tumor,
heart, brain and respiratory diseases. Trauma is the leading cause of the death
of young adults. At the same time, trauma has become a serious social problem in
peace time. Trauma throws great treats on human health and life. As an important
part in the medical and social security system, the emergency of trauma system
occupies a very important position in the emergency medical service system. In
European countries as well as the United States and also many other developed
countries, trauma service system had a long history, and progressed to an
advanced stage. However, Chinese trauma service system started late and is still
developing. It has not turned into a complete and standardized system yet. This
review summarizes the histories and current situations of the development of
traumatic first aid system separately in European countries, the United States
and our country. Special attentions are paid to the effects of the pre- and in
hospital emergency care. We also further try to explore the Chinese trauma
emergency model that adapts to the situations of China and characteristics of
different regions of China. Our review also introduces the trauma service system
that suits the situations of China proposed by Professor Jiang Baoguo's team in
details, taking Chinese conditions into account, they conducted a thematic study
and made an expert consensus on pre-hospital emergency treatment of severe
trauma, providing a basic routine and guidance of severe trauma treatment for
those pre-hospital emergency physicians. They also advised to establish
independent trauma disciplines and trauma specialist training systems, and to
build the regional trauma care system as well as the standards for graded
treatment, thus establishing a multiple disciplinary team (MDT) of severe trauma.
In this way, we can reduce the mortality and disability risks of severe trauma,
improve the quality of patients' life, and save more lives.
PMID- 28416853
TI - Changes in soluble sugar metabolism in loquat fruit during different cold
storage.
AB - To investigate soluble sugar metabolism and its relationship to chilling injury
(CI), loquat fruits were stored at 0 and 5 degrees C for 5 weeks. CI symptoms
were monitored during storage, and soluble sugar content and related enzyme
activities were measured. Enzymes activities and substrate levels in the
ascorbate-glutathione (AsA-GSH) cycle were also determined. Fruit at 0 degrees C
had lower sucrose levels and higher levels of glucose and fructose than fruit
maintained at 5 degrees C, and also manifested less severe CI symptoms. Fruit at
0 degrees C also exhibited increased activities of acid invertase, neutral
invertase, sucrose phosphatesynthase and sucrose synthase. AsA-GSH cycle activity
at 0 degrees C was much higher than that at 5 degrees C. Glucose levels
correlated positively with levels of AsA and GSH and ascorbate peroxidase (APX)
activity. The increased glucose levels are sufficient to account for the chilling
tolerance of loquat fruit.
PMID- 28416854
TI - Physicochemical, functionality and storage stability of hog plum (Spondia
pinnata) juice powder produced by spray drying.
AB - Hog plum juice powder was obtained from its juice under optimized condition by
spray drying with juice: maltodextrin ratio at 2:1, 4:1 and 6:1 (v/w) basis. The
inlet temperature and feed rate were varied between 120 to 175 degrees C and 8
to 14 mL/min. The effect of variables i.e. maltodextrin level, temperature and
feed rate on the physicochemical properties and total phenolic content were
studied. Moisture content, hygroscopicity, bulk density, water activity and total
phenolic content of the powder were significantly affected by inlet temperature
and maltodextrin level. However feed rate showed no any significant effect on the
bulk density of the powder. An increase in inlet temperature and maltodextrin
level reduced the total phenolic content in the spray dried powder. Morphological
study showed that at high inlet temperature the spray dried powder were of smooth
surfaces however, at low inlet temperature majority of the particles were of
shrivelled surfaces. Spray dried hog plum juice powder made with 3.9:1 juice:
maltodextrin, processed at 171 degrees C inlet temperature and at 8 mL/min feed
rate had less hygroscopicity, water activity, moisture content and potent TPC
content. Storage temperature significantly affected the TPC and DPPH free radical
scavenging activity of the powder. Refrigeration temperature was found to be more
effective to reduce the losses of TPC and DPPH free radical scavenging activity
during storage. Colour acceptability of the refrigerated sample was comparatively
more than to the sample stored at room temperature.
PMID- 28416855
TI - Production and characterization of functional properties of protein hydrolysates
from egg shell membranes by lactic acid bacteria fermentation.
AB - This study aimed to ferment the chicken eggshell membrane (ESM) using the lactic
acid bacteria, Lactobacillus plantarum for preparation of functional and
bioactive protein hydrolysates. Cultivation at an initial pH of 8.0 for 36 h
resulted in maximum protein concentration (177.3 mg/g) and degree of hydrolysis
(25.1%) of the hydrolysates. Fermentation resulted in the production of
hydrolysates that demonstrated excellent solubility (90.7%), good foaming
capacity (36.7%) and emulsification activity (94.6 m2/g). Additionally, these
protein hydrolysates exhibited remarkable bioactive properties for instance
reducing power (2.53), protection from DPPH radical (70.5%) and angiotensin I
converting enzyme inhibition (49.3%). The fermented protein hydrolysates were
also found effective against various foodborne pathogens. The protein
hydrolysates obtained by fermentation of ESM can be potentially incorporated in
functional foods and nutraceuticals resulting in valorization of the ESM waste.
PMID- 28416856
TI - Microbial analysis of MAP pot-stewed duck wings under different conditions during
15 degrees C storage.
AB - This study was to investigate the changes of microbial community and counts of
MAP pot-stewed duck wing (PSDW) under different packaging films and spices ratio
during 15 degrees C storage, using the traditional bacterial cultivation and PCR
DGGE. Results of microbial counting showed that the shelf-life of PDSW during 15
degrees C storage for recommendation was within six days, and the packaging films
and spices ratio didn't affect the change of microbial numbers in PSDW during
storage. PCR-DGGE analysis revealed that Staphylococcus equorum, Weissella sp.,
Leuconostoc mesenteroides became the dominating bacteria of PSDW at the end of
storage, and high barrier cover film, general barrier base film and spice ratio
1:1, had a better inhibition effect on bacteria in PSDW products, which could be
used as the condition for PSDW storage. This study will help PSDW processing
enterprises visualize the biodiversity of PSDW during storage, and choose the
best condition for the subsequent processing.
PMID- 28416857
TI - Compositional variability of nutrients and phytochemicals in corn after
processing.
AB - The result of various process strategies on the nutrient and phytochemical
composition of corn samples were studied. Fresh and cooked baby corn, sweet corn,
dent corn and industrially processed and cooked popcorn, corn grits, corn flour
and corn flakes were analysed for the determination of proximate, minerals,
xanthophylls and phenolic acids content. This study revealed that the proximate
composition of popcorn is high compared to the other corn products analyzed while
the mineral composition of these maize products showed higher concentration of
magnesium, phosphorus, potassium and low concentration of calcium, manganese,
zinc, iron, copper, and sodium. Popcorn was high in iron, zinc, copper,
manganese, sodium, magnesium and phosphorus. The xanthophylls lutein and
zeaxanthin were predominant in the dent corn and the total polyphenolic content
was highest in dent corn while the phenolic acids distribution was variable in
different corn products. This study showed preparation and processing brought
significant reduction of xanthophylls and polyphenols.
PMID- 28416858
TI - Study on E. coli and Salmonella biofilms from fresh fruits and vegetables.
AB - Foodborne outbreaks associated with fresh fruits and vegetables are on the rise
worldwide. Biofilm formation is one of the important traits of pathogens making
them strongly attached to substrates as well as express virulence phenotypes.
Present study investigates the biofilm forming ability of E. coli and Salmonella
sp. isolated from fresh fruits and vegetables. A total of 53 strains, including
35 E. coli and 18 Salmonella sp. isolated from different fruit and vegetable
samples were taken into account for the study. Initial screening for biofilm
formation was done using Congo Red agar plate test. Results revealed that 22.8%
E. coli and 22.2% Salmonella sp. were potential biofilm formers. However, the MTP
(Micro-Titre Plate) assay suggested more isolates of both E. coli and Salmonella
sp. were moderate to strong biofilm producers. Agar plate diffusion assay with
Agrobacterium tumefaciens NTL-4 showed the production of quorum signaling
molecules (AHLs) by three isolates of E. coli and one Salmonella sp. Two E. coli
isolates showed a significant amount of EPS production indicating higher biofilm
forming potential. The Presence of LUX R homologue gene (sdiA) in two of the
Salmonella isolates were confirmed by PCR which demonstrated their potential
pathogenicity. Results of the work underline the biofilm forming and potentially
virulent capacities of isolates from the surface of fruits and vegetables.
PMID- 28416859
TI - Effect of catechin and its derivatives on inhibition of polyphenoloxidase and
melanosis of Pacific white shrimp.
AB - This study aimed to investigate the effect of tea catechin (C) and 4 of its
derivatives on the Pacific white shrimp PPO inhibition and melanosis during
refrigerated storage. Epigallocatechin gallate (EGCG) exhibited the highest
inhibition towards PPO, followed by C. Inhibitory activity of all compounds
tested was in a dose dependent manner (0.1-2.0 mM). Based on activity staining,
EGCG most effectively inhibited PPO. For inhibition kinetic studies, C and
epicatechin (EC) showed uncompetitive type, whereas epicatechin gallate (ECG),
epigallocatechin (EGC) and EGCG exhibited mixed type inhibition. When whole
shrimps were treated with EGCG solution at various concentrations (0.25-0.75%),
those treated with 0.5 or 0.75% EGCG had lower melanosis scores throughout
storage for 10 days at 4 degrees C, compared with the control and the 1.25%
sodium metabisulfite treated samples (P < 0.05). Therefore, EGCG could be used as
a potential inhibitor for melanosis in raw Pacific white shrimp during
refrigerated storage.
PMID- 28416860
TI - Characterization of phenolic profile and antioxidant capacity of different fruit
part from lemon (Citrus limon Burm.) cultivars.
AB - Phenolic composition and antioxidant capacity of different fruit part including
peel, pulp, juice, whole fruit and seed from five lemon cultivars (Feiminailao,
Cuningmeng Limeng, Pangdelusaningmeng, Beijingningmeng) were investigated.
Caffeic acid (9.31-741.4 MUg/g FW) and chlorogenic acid (2.7-527.5 MUg/g FW) were
the dominant phenolic acid in fruit tested, Pangdelusaningmeng (PD) and Limeng
peels with the highest contents, respectively. Hesperidin was the predominant
flavanone (10.27-3315 MUg/g FW), Cuningmeng (CN) peels with the highest level. PD
peels had rich rutin, CN seeds had rich eriocitrin. Nobiletin was the main
polymethoxylated flavonoids identified, PD with the highest level. CN peels
contained rich tangeretin. Overall, peels and whole fruit had significantly
higher level of phenolics than other fruit parts, and seeds were good source of
flavonoids. PD and CN not only contained higher level of phenolic, but also
presented higher antioxidant capacity than other cultivars tested, and are of
great value for human nutrition.
PMID- 28416861
TI - Application of genetic algorithm to optimize extrusion condition for soy-based
meat analogue texturization.
AB - The aim of this study was to find the optimum extrusion process conditions for
texturized soybean meal as a meat analogue for food formulations using genetic
algorithm. The defatted soybean meal was replaced with whole soybean meal at 10%
and extruded in the temperature range of 150-200 degrees C, screw speed of 270
300 rpm and 20-25% feed moisture content based on the Box-Behnken design. The
barrel temperature effect was markedly greater than those of the feed moisture
content and screw speed on the product functional properties and appearance.
Higher temperatures led to a higher rehydration capacity, water and oil
absorption capacity, however, it had a negative effect on the product brightness.
It was found that the extrusion at lower moisture content improved soy protein
functionality. Genetic algorithm technique was applied to find the best process
conditions. The optimized process conditions were found to be the temperature of
198.8 degrees C, screw speed of 291 rpm and feed moisture content of 20.2%.
Overall, the whole soybean treatment was applicable to overcome the oil
separation issue during extrusion and the process was optimized to produce
texturized soy protein with the maximum attainable functionality.
PMID- 28416862
TI - Biscuits fortified with micro-encapsulated shrimp oil: characteristics and
storage stability.
AB - Characteristics and storage stability of biscuits fortified with micro
encapsulated shrimp oil (MSO) were determined. The addition of MSO increased
spread ratio, whilst decreased the thickness of biscuit. The highest hardness of
biscuit was obtained with addition of 9 or 12% MSO. Biscuit surface showed higher
redness and yellowness when MSO was incorporated (p < 0.05). The addition of MSO
up to 6% had no adverse effect on biscuit quality and acceptability. When
biscuits added with 6% MSO were stored under different illumination conditions
(light and dark), lipid oxidation in all samples increased throughout the storage
of 12 days. Light accelerated lipid oxidation of biscuits as evidenced by the
increases in both peroxide values and abundance of volatile compounds. No marked
change in EPA, DHA and astaxanthin contents were noticeable in biscuit fortified
with MSO after 12 days of storage. Therefore, the biscuit could be fortified with
MSO up to 6% and must be stored in dark to assure its oxidative stability.
PMID- 28416863
TI - Protective effects of tetrahydrocurcumin (THC) on fibroblast and melanoma cell
lines in vitro: it's implication for wound healing.
AB - The aim of this study was to investigate the role of tetrahydrocurcumin (THC)
against various skin health parameters using in vitro human foreskin fibroblast
and melanoma cell lines (i.e. HFF-1 and B16-F10). The study was assessed using
cell viability by MTT assay, identification of extracellular matrix component in
HFF-1 cell line (i.e. collagen, elastin and hyaluronic acid), melanin synthesis
in B16-F10 cells, cell viability against UVB-induced stress in HFF-1 cells, and
in vitro wound healing by the scratch assay. THC was found to be safe and
nontoxic up to the concentration of 10 ug/mL with improved level of collagen
(37.90%), elastin (90.1%), and hyaluronic acid (74.19%) at 1 ug/mL. Besides,
melanin was significantly inhibition by 78.5% at the lowest THC concentration of
0.1 ug/mL. UVB-protection rate was significantly improved by 61.2% and improved
cell viability by THC in HFF-1 cells, which indicated protection from photoaging.
In addition, THC showed significant wound healing activity (78.51%) and greater
migration of fibroblast in HFF-1 cells at different time period. It can be
concluded from the study that THC can protect the skin matrix with improved
extracellular component synthesis and would healing via collagen synthesis in the
skin, which improved the skin elasticity and tightness. Overall, it might be
suggested that THC can be used as a safe skin whitening agent, wounds management,
cosmetic applications, and treating various skin-related disorders.
PMID- 28416864
TI - Synthesis of structured lipids containing behenic acid from fully hydrogenated
Crambe abyssinica oil by enzymatic interesterification.
AB - Low-calorie structured lipids (SLs) rich in behenic and oleic acids were produced
by enzymatic (EI) and chemical interesterification (CI) of high oleic sunflower
oil and fully hydrogenated Crambe abyssinica oil in proportions of 60:40, 50:50,
40:60 and 30:70 (w/w), respectively. The immobilized lipase from Thermomyces
lanuginosus (Lipozyme TL IM) was used for 3 h at 70 degrees C at a dosage of 7%
(w/w) free of organic solvents. The original blend (BE) and the reaction products
were evaluated for their fatty acid (FA) and triacylglycerols (TAG) compositions,
solid fat contents, thermal analysis, regiospecific distribution of the FA,
microstructure and polymorphism. The tendency was towards a reduction in the C52,
C54, C60, C62 and C64 TAG contents and an increase in the C56, C58 e C66 TAG
contents, therefore the solid fat content was reduced. There was lower acyl
migration at the sn-2 position of the TAGs in EI as compared to CI in all the
blends ratios. Needle-like crystals were predominant in the IE while large
symmetrical spherulites were observed in the BE. Reduction in the mean crystal
diameter was observed in all the blends, in addition to modifications of the
crystal morphology. X-ray diffraction analysis showed a predominance of the beta'
form crystals in both the IE and CI. The SLs were produced for application in the
food industry as bakery/confectionery fats in the proportions of 60:40/50:50 and
as additive in the crystallization of lipids in the proportions of 40:60/30:70.
PMID- 28416865
TI - Folic acid content and antioxidant activity of different types of beers available
in Hungarian retail.
AB - In this study 40 Hungarian retail beers were evaluated for folic acid content,
antioxidant profile and physicochemical parameters. The physicochemical
parameters, folic acid content and antioxidant activity of alcohol-free beers
were the lowest. Folic acid content of beers aged with sour cherries showed high
values, more than 0.4 mg/l and an alcohol-free beer-based mixed drink made with
lemon juice contained more than 0.2 mg/l of folic acid. Dark beers and beers aged
with sour cherries had the highest antioxidant activity probably owing to their
high extract content, components released from the fruits and special malts.
These results highlight the possibility of achieving adequate folic acid and
relevant antioxidant intake without excessive alcohol and energy consumption by
selecting appropriate beer types.
PMID- 28416867
TI - Response surface optimization of low-fat ice cream production by using resistant
starch and maltodextrin as a fat replacing agent.
AB - In this research, maltodextrin (0, 1 and 2% w/w) and resistant starch (0, 1 and
2% w/w) were used in the formulation of low-fat ice cream (4% fat) and their
effects on the physicochemical and sensory properties were investigated. The
optimum levels of maltodextrin and resistant starch were determined by response
surface methodology. Increment of maltodextrin and resistant starch increased
acidity, viscosity, melting rate, time of dripping and overrun but decreased
melting rate of ice cream. Results showed that the incorporation of maltodextrin
and resistant starch at 0 and 2% w/w respectively, resulted into ice cream with
suitable viscosity, melting rate, first dripping time, overrun and acidity.
PMID- 28416866
TI - Rheology and microstructure of kefiran and whey protein mixed gels.
AB - The effect of kefiran on cold-set gelation of whey protein isolate (WPI) at 25
degrees C was studied using rheological measurements and environmental scanning
electron microscopy (ESEM). The gelation of samples was induced by the addition
of glucono-delta-lactone to the dispersions. WPI concentration was maintained at
8% (w/v) and the concentration of kefiran varied from 0 to 0.08% (w/v). According
to rheological measurements, the addition of kefiran into WPI dispersions
resulted in a significant increase in the gel strength, the yield stress, and the
shear stress values at the flowing point. The gelling point and gelation pH of
samples decreased significantly with an increase in kefiran concentration. ESEM
micrographs showed that the presence of kefiran played an important role in the
microstructure formation of gels. The microstructure of kefiran-WPI mixed gels
was more compact and dense, compared to the WPI gel. Depletion interactions
between kefiran and whey protein aggregates can be regarded as the chief factor
which was responsible for these effects. The present work demonstrated that
rheological and microstructural properties of acid-induced whey protein gels were
improved by the addition of kefiran.
PMID- 28416868
TI - A synergistic effect of Cremophor and beta glucosylceramide to exert liver and
sugar protection.
AB - Many commonly used drugs carry the potential to induce hepatotoxicity, and a
large number of foods and beverages induce an increase in blood sugar levels. A
change in lifestyle by omitting these compounds is not applicable in many
circumstances. beta-Glucosylceramide (GC) is a naturally occurring
glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL)
is a synthetic, nonionic surfactant that is used as a vehicle for the
administration of water-insoluble compounds. The aim of the present study was to
determine the synergistic effect of oral administration of the combination of GC
and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched
compounds. Four groups of mice, treated with PBS, GC, CrEL, or GCC were studied
in the concanavalin A immune-mediated hepatitis model, in the acetaminophen
(APAP) toxicity model, and as additives to two types of sugar-enriched soda
drinks. Both GC and CrEL exerted hepatoprotective effects in the ConA hepatitis
and APAP toxicity models. Moreover, in both models, GCC exerted a synergistic
effect in ameliorating liver damage as manifested by a significant decrease in
the ALT serum levels. When added to two types of sugar-enriched sodas, GCC
exerted a synergistic effect in ameliorating the increase in blood sugar levels.
GCC exerts synergistic hepatoprotective and glucose-protective effects in models
of liver damage and increased serum glucose. GCC can provide liver and sugar
protection when co-administered with hepatotoxic drugs or sugar-enriched drinks.
PMID- 28416869
TI - Effects of ethyl oleate and microwave blanching on drying kinetics of bitter
gourd.
AB - In the present study effects of pre-treatments such as blanching with hot water
and microwave, ethyl oleate dipping, and combinations of these treatments on
drying characteristics of the bitter gourd (Momordica charantia L.) at various
temperature were studied. The overall drying time was reduced significantly in
the ethyl oleate treated and microwave blanched samples. The minimum diffusivity
(2.65 * 10-8 m2/s) was observed in control samples whereas the maximum
diffusivity (3.86 * 10-8 m2/s) was observed in ethyl oleate treated and microwave
blanched samples at 50 degrees C. Ethyl oleate treated and microwave blanched
samples dried at lowest temperature (50 degrees C) showed the lowermost
shrinkage ratio (46.04%). The rehydration ratio increased from 3.49 to 4.90 as
the temperature increased from 50 to 70 degrees C for control samples. Combined
pre-treatment of ethyl oleate and microwave blanching had resulted in most
acceptable drying characteristics and quality of bitter gourd. Drying of the
samples were mathematically modelled. The drying characteristics of bitter gourd
could be explained suitably by Page drying model.
PMID- 28416870
TI - Antagonistic activity of Thymus vulgaris extracts against Vibrio species isolated
from seafoods.
AB - This study examined the antibacterial activity of Thymus vulgaris on multiple
antibiotic resistant (MAR) Vibrio parahaemolyticus and Vibrio fluvialis isolated
from shrimps. The ethanol extract of T. vulgaris antibacterial properties was
assessed using the agar diffusion method. Survival of test organisms in shrimp
meat using different concentrations of T. vulgaris was done using standard
method. The quantitative and qualitative phytochemical tests of T. vulgaris
extract were determined. The ethanol extract had antimicrobial activities on the
test organisms showing 20.00 +/- 0.0 and 23.00 +/- 0.0 mm zone of inhibition on
V. parahaemolyticus and V. fluvialis respectively. T. vulgaris completely
decreased microbial load of V. parahaemolyticus and V. fluvialis in 150 and 60
min, respectively. The phytochemical screening for the ethanol extract reported
phenol, alkaloids, tannin, saponin, anthraquinone flavonoid and cardiac glycoside
as 51.76, 26.60, 6.76, 54.33, 30.35 89.65 and 18.23 mg/100 g, respectively. This
study reveals the antibacterial property of T. vulgaris on the MAR Vibrio
species.
PMID- 28416871
TI - Effect of water quality on the main components in Fuding white tea infusions.
AB - The aim of this study was to investigate the effect of water quality on the main
components in Fuding white tea infusions, including catechins, caffeine, theanine
and free amino acids. Pure, tap and spring water were tested, and water quality
was found to have a distinct effect on the main compounds extracted. Pure water,
which was weakly acidic and low in dissolved ions, achieved the highest catechin
content, whereas caffeine and theanine, and amino acids, were higher in infusions
made with spring and tap water, respectively. Sensory evaluation was performed to
evaluate infusion colour, taste and aroma, and sensory quality was similarly
influenced by water type, due primarily to differences in dissolved ions. Pure
water was more suitable for brewing white tea with superior colour, aroma and
taste.
PMID- 28416872
TI - Impact of light irradiation on black tea quality during withering.
AB - Black tea manufacture usually involves the processes of withering, cutting,
fermentation and drying. The aim of present study was to evaluate the effect of
the relationship between the quality and withering with different light sources
(ultraviolet, yellow, blue, purple, orange, red, cyan, green and white) an
quality attribute of tea. The results indicated that the yellow, orange and red
light withering significantly improved the aroma and taste, imparting the tea a
sweet flavor and a fresh and mellow taste. Tea treated with yellow light was
scored highest the sensory scores and showed the highest content in catechins,
theaflavins, amino acids and aroma components, followed by the orange and red
light treatments. The black tea withered with ultraviolet light showed a strong
astringency, probably resulting from low contents of theaflavins, amino acids and
soluble sugar. The green light irradiation remarkably damaged the aroma and taste
of the tea, leading to a strong greenish flavor and an astringent taste, probably
owing to the lowest contents of chemical compositions. No significant cumulative
effect was found in the hybrid light withering treatments. Therefore,
monochromatic yellow, orange and red lights were suggested for withering the
black tea to improve its overall quality.
PMID- 28416873
TI - Collagen extraction from mussel byssus: a new marine collagen source with
physicochemical properties of industrial interest.
AB - Mussel byssus is a by-product of mussel production and is a potential source of
collagen. The goal of this study was to extract collagen from the byssus of
Chilean mussel using an enzymatic method and characterize it. A pepsin-aided
extraction method was employed where first an enzymatic hydrolysis at two
pepsin/substrate ratios (1:50 or 4:50) and times (4 or 24 h) was done. Extraction
was conducted at 80 degrees C for 24 h, in a 0.5 N acetic acid solution. All
samples were analyzed for collagen content, amino acid profile, turbidity,
viscosity, solubility, denaturation temperature and surface tension. Hydrolysis
time had significant effect on collagen content, hydroxyproline content and
extraction yield. Hydrolysis with a pepsin/byssus ratio of 4:50 for 24 h gave the
better extraction performance with values of 69 mg/g protein, 1.8 mg/g protein
and 30%, for collagen content, hydroxyproline content and extraction yield,
respectively. No differences were found for the viscosity and surface tension of
collagen dispersions, suggesting that the enzymatic hydrolysis did not affect the
integrity of the collagen molecule. Denaturation temperature of freeze-dried
byssus collagen presented a high value (83-91 degrees C), making this kind of
collagen a very interesting material for encapsulation of bioactive molecules and
for biomedical applications.
PMID- 28416874
TI - Effect of microwave drying on quality kinetics of okra.
AB - The effects of microwave drying on quality attribute of okra were evaluated.
Microwave power values show significant effect on moisture diffusivity, color,
hardness and sensory attributes of dried okra. The total color change ([Formula:
see text]) increased whereas [Formula: see text], [Formula: see text] and
[Formula: see text] decreased with an increase in both power and time. The
kinetics of [Formula: see text] and [Formula: see text] were well expressed by
zero-order kinetic models, while [Formula: see text] and [Formula: see text]
followed first-order kinetic models. Hardness was expressed by a first-order
kinetic model. Sensory evaluation showed that okra dried at 800 W was most
attractive in terms of color, texture, flavor and overall liking. Microwave
drying at 800 W presented the shortest drying time with the least change in
hardness, but the most change in color. Thus, high-power microwave drying
potentially produces dried fruits and vegetables with minimum changes in
hardness.
PMID- 28416875
TI - Hawberry (Crataegus monogyna Jaqc.) extracts inhibit lipid oxidation and improve
consumer liking of ready-to-eat (RTE) pork patties.
AB - The objective of this work was to study the effectiveness of extracts from
hawberry (Crataegus monogyna Jacq.) to inhibit lipid oxidation and odor
deterioration during processing of ready-to-eat (RTE) pork patties subjected to
roasting (180 degrees C/16 min), chilling (10 days/+3 degrees C) and reheating
in microwave (600 mW/1 min). Acetone extracts of hawberry were chosen based on
their total phenolic content (1281.1 +/- 84.8 mg gallic acid equivalent (GAE)/100
g fruit) and in vitro antiradical activity (DPPH) (53.33 +/- 15.40 g equivalent
Trolox per g of fruits). Pork patties treated with increasing concentrations of
hawberry extract, 200 and 800 ppm GAE (T2 and T8, respectively) and a control
group (T0) of samples, were analyzed for TBARS, volatile carbonyls and odor
liking in a consumer test. Hawberry extracts significantly improved the oxidative
stability of cooked pork patties keeping TBARS and hexanal counts at basal levels
during the whole process. The addition of hawberry phenolic-rich extracts
significantly improved the degree of consumer satisfaction regarding the odor of
patties. In conclusion, the hawberry extract displayed potential usage as an
ingredient with antioxidant properties for the manufacture of high-quality RTE
meat products.
PMID- 28416876
TI - Comparison of rheological behaviors and nanostructure of bighead carp scales
gelatin modified by different modification methods.
AB - In this study, microbial transglutaminase (MTGase) and pectin were compared to
modify bighead carp (Hypophthalmichthys nobilis) scale gelatin. The functional
properties of modified fish scales gelatin (FSG) were largely improved, including
melting temperature and rheological behavior. While, modification methods
decreased the triple-helix content and destroyed the single left-hand helix chain
of modified FSG as investigated by X-ray diffraction. MTGase could induce the
denser and finer gels network, but had none significant effect on nanostructural
properties of fish gelatin. Pectin inserted itself into the fish gelatin gels
network and caused aggregations, forming crystalline peaks and various
nanostructures. In particular, compared with pectin modified FSG, MTGase produced
FSG with lower storage modulus and apparent viscosity, but higher gel points and
melting points.
PMID- 28416877
TI - Quality, antioxidant activity and composition of Indian black teas.
AB - A comparative study was undertaken to determine the difference in quality,
antioxidant activity, and mineral content of northern and southern Indian tea
varieties. The results showed that the antioxidant activity, theaflavin and
thearubigin content, color particle size and total soluble solids influence the
tea leaf and tea dust. Assam leaf showed higher values for all the physico
chemical properties followed by Darjeeling leaf. In addition, the mineral
composition of the tea infusion was also influenced. The preparation method,
including the amounts of tea and water used, infusion time was shown to be a
major determinant of the component concentrations of tea beverages as consumed.
An illustration of the variation introduced by these varieties of tea is provided
by comparing solids, caffeine, minerals and antioxidant activity of black teas
available locally.
PMID- 28416878
TI - Imitation of soymilk-cow's milk mixed enzyme modified cheese: their composition,
proteolysis, lipolysis and sensory properties.
AB - Combined use of soymilk-cow's milk is a novel approach in food industry and has
great potential to developed products with numerous health benefits. This study
aimed to develop the enzyme-modified cheeses (EMCs) using soymilk-cow's milk. The
curd was hydrolysed using combination of proteinases/peptidase to produce a range
of proteolysed products followed by lipolysis to create flavoured EMCs. Results
showed that enzymes led to an increase in amino acids (AA), free fatty acids
(FFA), complex volatiles, and improved sensory attributes. The EMCs showed higher
mean values of AA, FFA and volatile compounds when prepared using Flavourzyme(r)
in combination with Lipases AY30 and DF15. EMCs were less eggy, bitter, pungent,
more buttery, saltier, nutty, and had sweet sensory characteristics. Overall,
results demonstrated the potential of combined matrix to create a range of
flavoured EMCs for a wider range of consumers.
PMID- 28416879
TI - Supercritical CO2 extraction of candlenut oil: process optimization using Taguchi
orthogonal array and physicochemical properties of the oil.
AB - A series of experiments was conducted to determine optimum conditions for
supercritical carbon dioxide extraction of candlenut oil. A Taguchi experimental
design with L9 orthogonal array (four factors in three levels) was employed to
evaluate the effects of pressure of 25-35 MPa, temperature of 40-60 degrees C,
CO2 flow rate of 10-20 g/min and particle size of 0.3-0.8 mm on oil solubility.
The obtained results showed that increase in particle size, pressure and
temperature improved the oil solubility. The supercritical carbon dioxide
extraction at optimized parameters resulted in oil yield extraction of 61.4% at
solubility of 9.6 g oil/kg CO2. The obtained candlenut oil from supercritical
carbon dioxide extraction has better oil quality than oil which was extracted by
Soxhlet extraction using n-hexane. The oil contains high unsaturated oil
(linoleic acid and linolenic acid), which have many beneficial effects on human
health.
PMID- 28416880
TI - Frying of rice flour dough strands containing gum Arabic: texture, sensory
attributes and microstructure of products.
AB - The effects of rice flour (50-56%, w/w) and gum Arabic (0-5%, w/w) on the
physical, sensory and structural features of the fried dough strands were
investigated. Up to 25.8% reduction in oil was possible by the incorporation of
gum Arabic. The wide variations in failure force (13.8-25.3 N) and failure strain
(11.0-28.6%) indicated the formation of snacks varying in texture from a soft-to
bite brittle product to a hard-to-eat less brittle sample. The snacks possessed a
porous microstructure with air cells, pores and vacuoles; the cell walls were
more than 100 MUm in thickness. The textural parameters like failure force,
failure energy and failure stress behaved in a similar manner in the principal
component analysis biplot. High moisture content in the dough decreased the
sensory acceptance of the fried snacks. The high desirability index of 0.9 could
be achieved with a high level of rice flour (56%, w/w) while gum Arabic content
was between 3.50 and 3.75% (w/w).
PMID- 28416881
TI - Use of chitosan coating in increasing the shelf life of liquid smoked Nile
tilapia (Oreochromis niloticus) fillet.
AB - The aim of this research was to evaluate the efficiency of liquid smoking and
chitosan coating on the shelf life of Nile tilapia (Oreochromis niloticus)
fillets. Fillets without liquid smoked and chitosan coating (control), liquid
smoked fillets (LS), and liquid smoked and chitosan coated fillets (LSCh) were
stored at 4 +/- 1 degrees C for 30 days. The physicochemical (pH, moisture
content, water activity-aw, color, texture, total volatile bases nitrogen-TVB-N
and thiobarbituric acid reactive substances-TBARS) and microbiological analyses
(mesophilic and psychrotrophic counts) and the electrophoresis profile of samples
were carried out. Physicochemical parameters, such as TVB-N and TBARS, were
reduced in the tilapia fillets with liquid smoking. The presence of the coating
of chitosan was effective for the control of the microorganisms during storage.
This work showed that the addition of a chitosan coating in liquid-smoked fillets
further enhanced the effect of preservation.
PMID- 28416882
TI - Chemical composition, antiproliferative and antioxidant activity of differently
processed Ganoderma lucidum ethanol extracts.
AB - The content of phenolic compounds (TPC) and glucans, as well as the effectiveness
of antiproliferative and antioxidant activity of differently processed Ganoderma
lucidum ethanol extracts were determined and compared. The content of glucans
(total, alpha- and beta-) strongly depended on the extraction time and particle
size, but only interaction of these parameters influenced the TPC. Gallic acid,
quercetin, trans-cinnamic acid, kaempferol, hesperetin and naringenin were
detected in extracts by HPLC-DAD. The most abundant phenols were hesperetin
(1.875-3.222 ug/g) and naringenin (1.235-2.856 ug/g). The ethanol extracts
exhibited noteworthy antioxidant activity, but the significant amount of phenolic
compounds was strongly linked to polysaccharides, and hence reduced their
antioxidant capacity. The results of the antiproliferative activity in vitro
showed that the analyzed extracts were the most effective against HeLa cells.
Significant correlations were observed between the antiproliferative effect and
the TPC/glucan content of extracts.
PMID- 28416883
TI - Application of electrolysed oxidising water as a sanitiser to extend the shelf
life of seafood products: a review.
AB - Electrolysed oxidising water (E.O. water) is produced by electrolysis of sodium
chloride to yield primarily chlorine based oxidising products. At neutral pH this
results in hypochlorous acid in the un-protonated form which has the greatest
oxidising potential and ability to penetrate microbial cell walls to disrupt the
cell membranes. E.O. water has been shown to be an effective method to reduce
microbial contamination on food processing surfaces. The efficacy of E.O. water
against pathogenic bacteria such as Listeria monocytogenes, Escherichia coli and
Vibrio parahaemolyticus has also been extensively confirmed in growth studies of
bacteria in culture where the sanitising agent can have direct contact with the
bacteria. However it can only lower, but not eliminate, bacteria on processed
seafoods. More research is required to understand and optimise the impacts of
E.O. pre-treatment sanitation processes on subsequent microbial growth, shelf
life, sensory and safety outcomes for packaged seafood products.
PMID- 28416884
TI - Determination of soluble dietary fibre content of Okara treated with high
hydrostatic pressure and enzymes: a comparative evaluation of two methods (AOAC
and HPLC-ELSD).
AB - ABSTRACT: Okara is a promising by-product from soybean and a rich source of
dietary fibre, chiefly insoluble (IDF). To increase its solubility and
functionality, a treatment with high hydrostatic pressure (HHP) assisted by food
grade enzymes -Ultraflo(r) L or Viscozyme(r) L- has been performed. To monitor
the effectiveness, an analysis of dietary fibre, mainly the soluble fraction
(SDF), was accomplished by the AOAC enzymatic-gravimetric method with dialysis
followed by both, spectrophotometric methods and High Performance Liquid
Chromatography with Evaporative Light Scattering Detector (HPLC-ELSD) analysis of
the soluble fraction. A significant increase in SDF (~1.5-times) to the expense
of a decrease in IDF was shown and chromatograms revealed two peaks of 95 and 22
kDa. Thus, treated Okara possessed a more balanced and convenient ratio of
soluble to insoluble dietary fibre, which could have health benefits as
prebiotic. Inbuilt interferences of the official AOAC's method for dietary fibre
were confirmed and the direct HPLC-ELSD approach was about twice more sensitive
than spectrophotometric methods. Consequently, the direct HPLC-ELSD analysis of
the supernatant is proposed as a cheaper, faster and reliable method. Combined
HHP-treatments plus specific enzymes represent a promising alternative for the
valorisation and preservation of agrofood by-products. GRAPHICAL ABSTRACT:
PMID- 28416885
TI - Effect of chitosan treatment on strawberry allergen-related gene expression
during ripening stages.
AB - The effectiveness of a chitosan coating treatment on the allergen-related genes
expression of three strawberry cultivars (Fragaria * ananassa Duch., namely cvs.
"Sabrina", "Candonga" and "Jonica") harvested at three ripening stages was
evaluated. Fruits were treated with a 1% chitosan coating and stored at 20
degrees C for 48 h. Three genes, encoding Fra a1, Fra a3 and Fra a4 allergens,
were evaluated by real-time qPCR. The transcript levels of several genes showed
different patterns during ripening stages in strawberry cultivars but were up
regulated by chitosan treatment.
PMID- 28416886
TI - Optimization of reuterin production in cheese by Lactobacillus reuteri.
AB - Cheeses manufactured from pasteurized milk supplemented with glycerol and
reuterin-producing Lactobacillus reuteri INIA P572 as adjunct to the commercial
starter culture were analysed in order to optimize a biopreservation strategy.
The highest reuterin concentration determined by a colorimetric assay was
detected on day 1 in cheeses with 100-500 mM glycerol. The presence of reuterin
was confirmed by a direct detection technique as HPLC. Cheeses made with L.
reuteri and 200 or 500 mM glycerol showed a red tendency in color in comparison
with control. The results with purified reuterin suggested that the development
of slightly rosy colour in cheese was related to some compound
produced/overproduced when higher levels of glycerol were present in cheese, but
not due to reuterin. Application of L. reuteri INIA P572 as adjunct to the
commercial starter with 100 mM glycerol led to such a reuterin concentration in
cheese that could control undesirable microorganisms, avoiding the presence of
color-changing compounds.
PMID- 28416887
TI - A preliminary study of PCBs, PAHs, pesticides and trace metals contamination in
cold-pressed rapeseed oils from conventional and ecological cultivations.
AB - The purpose of this study was to investigate the levels of polycyclic aromatic
hydrocarbons [benzo(a)anthracene, chrysene, benzo(b)fluoranthene, and
benzo(a)pyrene], polychlorinated biphenyls (6 marker and 12 dioxin-like),
pesticides (74 compounds) and heavy metals (Pb, Cd, As, Hg, Fe, Cu), in the cold
pressed rapeseed oils from conventional (RC) and ecological cultivations (RE).
Similar level of PAHs, PCBs and heavy metals was found in the investigated cold
pressed oils; moreover, no effect of rapeseeds cultivation practice on the level
of pesticide residues was found. Levels of PAHs, PCBs, and pesticides were within
EU legislation limits. Concentration of 4 PAHs oscillated between 3.13 and 6.15
MUg/kg, concentration of non-dioxin-like PCBs was within 2599.4-8380.8 pg/g
range, dioxin-like PCSs levels varied from 310.2 to 819.4 pg/g (0.307-0.780 pg
TEQ/g oil). Iron (Fe) and copper (Cu) were prevailing heavy metals found in the
studied oils (0.236-1.690 mg/kg range, 0.036-0.062 mg/kg range, respectively).
Measured lead (Pb) contents reached (RC1) or were nearly equal to the EU limit of
0.1 mg/kg (RE1 and RE2).
PMID- 28416888
TI - Tailoring Pore Size and Chemical Interior of near 1 nm Sized Pores in a
Nanoporous Polymer Based on a Discotic Liquid Crystal.
AB - A triazine based disc shaped molecule with two hydrolyzable units, imine and
ester groups, was polymerized via acyclic diene metathesis in the columnar
hexagonal (Colhex) LC phase. Fabrication of a cationic nanoporous polymer (pore
diameter ~1.3 nm) lined with ammonium groups at the pore surface was achieved by
hydrolysis of the imine linkage. Size selective aldehyde uptake by the cationic
porous polymer was demonstrated. The anilinium groups in the pores were converted
to azide as well as phenyl groups by further chemical treatment, leading to
porous polymers with neutral functional groups in the pores. The pores were
enlarged by further hydrolysis of the ester groups to create ~2.6 nm pores lined
with -COONa surface groups. The same pores could be obtained in a single step
without first hydrolyzing the imine linkage. XRD studies demonstrated that the
Colhex order of the monomer was preserved after polymerization as well as in both
the nanoporous polymers. The porous anionic polymer lined with -COOH groups was
further converted to the -COOLi, -COONa, -COOK, -COOCs, and -COONH4 salts. The
porous polymer lined with -COONa groups selectively adsorbs a cationic dye,
methylene blue, over an anionic dye.
PMID- 28416889
TI - Predicting toddler temperamental approach-withdrawal: Contributions of early
approach tendencies, parenting behavior, and contextual novelty.
AB - Research suggests that temperamental approach-withdrawal is subject to parenting
influences, but few studies have explored how specific parenting behaviors and
contextual novelty contribute to the observed pattern of effects. The present
study examined associations between infant temperamental approach, mother
behavior while introducing novel objects (12 months) and temperamental approach
withdrawal in toddlerhood (18 months) in a sample of 132 infants (68 males).
Maternal positive affect predicted more toddler approach-withdrawal for high
approach infants and maternal stimulation predicted less toddler approach
withdrawal for low-approach infants; however, these patterns varied with
intensity of novelty in both parenting and toddler outcome contexts. Thus,
maternal behavior may lead to stronger associations between earlier and later
measures of approach-withdrawal; however, these effects are tied to contexts of
measurement.
PMID- 28416890
TI - Relationship between perceived exertion during exercise and subsequent recovery
measurements.
AB - The return towards resting homeostasis in the post-exercise period has the
potential to represent the internal training load of the preceding exercise bout.
However, the relative potential of metabolic and autonomic recovery measurements
in this role has not previously been established. Therefore the aim of this study
was to investigate which of 4 recovery measurements was most closely associated
with Borg's Rating of Perceived Exertion (RPE), a measurement widely acknowledged
as an integrated measurement of the homeostatic stress of an exercise bout. A
heterogeneous group of trained and untrained participants (n = 36) completed a
bout of exercise on the treadmill (3 km at 70% of maximal oxygen uptake) followed
by 1 hour of controlled recovery. Expired respiratory gases and heart rate (HR)
were measured throughout the exercise and recovery phases of the trial with
recovery measurements used to calculate the magnitude of excess post-exercise
oxygen consumption (EPOCMAG), the time constant of the EPOC curve (EPOCtau), 1
min heart rate recovery (HRR60s) and the time constant of the HR recovery curve
(HRRtau) for each participant. RPE taken in the last minute of exercise was
significantly associated with HRR60s (r=-0.69), EPOCtau (r=0.52) and HRRtau
(r=0.43) but not with EPOCMAG. This finding suggests that, of the 4 recovery
measurements under investigation, HRR60s shows modest potential to represent
inter-individual variation in the homeostatic stress of a standardized exercise
bout, in a group with a range of fitness levels.
PMID- 28416891
TI - Session-RPE for quantifying the load of different youth basketball training
sessions.
AB - The aim of the study was to evaluate youth basketball training, verifying the
reliability of the session-RPE method in relation to session duration (< and >=
80 minutes) and workout typology (reduced and high warm-up, conditioning,
technical, tactical, game portions within a single session) categories. Six male
youth basketball players (age, 16.5+/-0.5 years; height, 195.5+/-6.75 cm; body
mass, 93.9+/-10.9 kg; and body mass index, 23.6+/-2.8 kg.m-2) were monitored (HR,
type and duration of workouts) during 15 (66 individual) training sessions (80+/
26 minutes). Edwards' HR method was used as a reference measure of internal
training load (ITL); the CR-10 RPE scale was administered 30 minutes after the
end of each session. The results obtained showed that all comparisons between
different session durations and workout portions revealed effects in term of
Edwards' ITLs except for warm-up portions. Moderate to strong relationships
between Edwards' and session- RPE methods emerged for all sessions (r = .85, P <
.001), player's sessions (r range = .79 - .95, P < .001), session durations (< 80
minutes: r = .67, P < .001; >= 80 minutes: r = .75, P < .001), and workout
portions (r range = .78 - .89, P range = .002 - < .001). The findings indicated
that coaches of youth basketball players can successfully use session-RPE to
monitor the ITL, regardless of session durations and workout portions.
PMID- 28416892
TI - Anthropometric and physical characteristics allow differentiation of young female
volleyball players according to playing position and level of expertise.
AB - The aim of our study was to determine the differences in some anthropometric and
physical performance variables of young Croatian female volleyball players (aged
13 to 15) in relation to playing position (i.e., independent variable) and
performance level within each position (i.e., independent variable). Players were
categorized according to playing position (i.e., role) as middle blockers (n=28),
opposite hitters (n=41), passer-hitters (n=54), setters (n=30), and liberos
(n=28). Within each position, players were divided into a more successful group
and a less successful group according to team ranking in the latest regional
championship and player quality within the team. Height and body mass, somatotype
by the Heath-Carter method, and four tests of lower body power, speed, agility
and upper body power (i.e., dependent variables) were assessed. Players in
different positions differed significantly in height and all three somatotype
components, but no significant differences were found in body mass, body mass
index or measured physical performance variables. Players of different
performance level differed significantly in both anthropometric and physical
performance variables. Generally, middle blockers were taller, more ectomorphic,
less mesomorphic and endomorphic, whereas liberos were shorter, less ectomorphic,
more mesomorphic and endomorphic than players in other positions. More successful
players in all positions had a lower body mass index, were less mesomorphic and
endomorphic, and more ectomorphic than less successful players. Furthermore, more
successful players showed better lower body power, speed, agility and upper body
power. The results of this study can potentially provide coaches with useful
indications about the use of somatotype selection and physical performance
assessment for talent identification and development.
PMID- 28416894
TI - Letter to the editor: A genetic-based algorithm for personalized resistance
training.
AB - In a recent paper entitled "A genetic-based algorithm for personalized resistance
training", Jones et al. [1] presented an algorithm of 15 performance-associated
gene polymorphisms that they propose can determine an athlete's training response
by predicting power and endurance potential. However, from the design of their
studies and the data provided, there is no evidence to support these authors'
assertions. Progress towards such a significant development in the field of sport
and exercise genomics will require a paradigm shift in line with recent
recommendations for international collaborations such as the Athlome Project (see
www.athlomeconsortium.org). Large-scale initiatives, involving numerous multi
centre and well-phenotyped exercise training and elite performance cohorts, will
be necessary before attempting to derive and replicate training and/or
performance algorithms.
PMID- 28416893
TI - Letter to the editor: Are the doors opened to a genetic-based algorithm for
personalized resistance training?
PMID- 28416895
TI - A response to letter to the editor: A genetic-based algorithm for personalized
resistance training.
PMID- 28416896
TI - ACTN3 R577X genotype and performance of elite middle-long distance swimmers in
China.
AB - The ACTN3 gene is one of the genes that have a potential influence on physical
performance. Studies have shown that the 577R genotype of ACTN3 is more prevalent
in sprint athletes, while the 577X genotype is more prevalent in endurance
athletes. In swimming, both power and endurance related phenotypes are equally
needed for swimmers to excel at the elite level. Therefore, the ACTN3 R577X
polymorphism may become a genetic marker for swimmers. The study aimed to examine
the association of the ACTN3 R577X genotype with the performance of elite middle
long distance (MLD) swimmers. The distributions of the ACTN3 R577X (rs1815739)
genotype and allele were examined in a general population (206) and a group of
elite MLD swimmers (160) in China by using PCR-RFLP and TOF. Compared with the
general population, the elite MLD swimmers, especially the females, had a higher
frequency of the RR genotype. The swimmers had a higher frequency of the R allele
than the general population. However, the difference was not statistically
significant. After being stratified by performance, the difference of the R
allele frequency between the international master athletes and the general
population was statistically significant. The elite MLD swimmers had a higher
frequency of the RR genotype than the RX+XX genotype compared with the general
population. The ACTN3 R577X polymorphism was associated with the performance of
elite MLD swimmers in China. The SNP R577X could be used as a biomarker for
selecting elite MLD swimmers in China.
PMID- 28416897
TI - Total bilirubin in athletes, determination of reference range.
AB - The purpose of this study was to determine a typical reference range for the
population of athletes. Results of blood tests of 339 athletes (82 women and 257
men, aged 18-37 years) were retrospectively analysed. The subjects were
representatives of different sports disciplines. The measurements of total
bilirubin (BIT), iron (Fe), alkaline phosphatase (ALP), alanine aminotransferase
(ALT) and gamma-glutamyltransferase (GGT) were made using a Pentra 400
biochemical analyser (Horiba, France). Red blood cell count (RBC), reticulocyte
count and haemoglobin concentration measurements were made using an Advia 120
haematology analyser (Siemens, Germany). In groups of women and men the
percentage of elevated results were similar at 18%. Most results of total
bilirubin in both sexes were in the range 7-14 MUmol.L-1 (49% of women and 42% of
men). The highest results of elevated levels of BIT were in the range 21-28
MUmol.L-1 (12% of women and 11% of men). There was a significant correlation
between serum iron and BIT concentration in female and male athletes whose serum
total bilirubin concentration does not exceed the upper limit of the reference
range. Elevated concentrations of total bilirubin appear to be due to changes
caused by regular exercise. The obtained upper limit of the reference range for
total bilirubin concentration in the group of athletes is 29.0 MUmol.L-1. It
seems reasonable to use dedicated reference values for total bilirubin
concentration in relation to the group of athletes.
PMID- 28416898
TI - SIgA response and incidence of upper respiratory tract infections during
intensified training in youth basketball players.
AB - The aim of the present study was to examine the effect of an intensified training
phase followed by a tapering phase on the salivary immunoglobulin A concentration
and on the upper respiratory tract infection (URTI) symptoms in young male
basketball players. The session rating of perceived exertion method was used to
quantify the internal training load, and the Wisconsin Upper Respiratory Symptom
Survey-21 questionnaire was used to assess URTI symptoms. The Yo-Yo IR1 test and
saliva collection were carried out at the beginning of the study (T1), after the
intensified phase (T2), and after tapering (T3). A higher internal training load
was observed for the intensified phase compared with the tapering phase (t=19.10;
p<0.001), and a significant decrease in salivary immunoglobulin A concentration
was detected (F=7.48; p=0.004) at T3 compared to T1 (p=0.02) and T2 (p=0.05).
However, there was no significant difference between phases for severity of URTI
(chi2= 2.83; p=0.242). The Yo-Yo IR1 test performance increased from T2 and T3
compared to T1 (F=58.24; p<0.001). There was no significant effect of aerobic
fitness level on salivary immunoglobulin A response (F=1.095; p=0.344). In
summary, the present findings suggest that an intensified training load followed
by a tapering period negatively affects the mucosal immune function with no
significant change in severity of URTI in young basketball players.
PMID- 28416899
TI - The efficacy of a discontinuous graded exercise test in measuring peak oxygen
uptake in children aged 8 to 10 years.
AB - As children's natural activity patterns are highly intermittent in nature, and
characterised by rapid changes from rest to vigorous physical activity,
discontinuous exercise tests may be considered ecologically valid for this
population group. This study compared the peak physiological responses from a
discontinuous and continuous graded exercise test (GXT_D, GXT_C, respectively)
during treadmill exercise in children. Twenty-one healthy children (9.6 +/- 0.6
y) completed GXT_D and GXT_C in a randomised order, separated by 72-hours.
Following each GXT, and after a 15-minute recovery, participants completed a
verification test at 105% of the velocity attained at peak oxygen consumption
(VO2peak). There were no differences in VO2peak (55.3 +/- 8.2 cf. 54.4 +/- 7.6
mL.kg-1.min-1) or maximal heart rate (202 +/- 10 cf. 204 +/- 8 b.min-1) between
GXT_C and GXT_D, respectively (P>.05). Peak running speed (10.7 +/- 0.9 cf. 12.1
+/- 1.3 km.h-1) and respiratory exchange ratio (1.04 +/- 0.05 cf. 0.92 +/- 0.05)
were however different between tests (P<.001). Although similar peak
physiological values were revealed between GXT_C and the corresponding
verification test (P>.05), VO2peak (53.3 +/- 7.3 mL.kg-1.min-1) and heart rate
(197 +/- 13 b.min-1) were significantly lower in the GXT_D verification test
(P<.05). In conclusion, a discontinuous GXT is an accurate measure of VO2peak in
children aged 8 to 10 years and may be a valid alternative to a continuous GXT,
despite its longer duration.
PMID- 28416900
TI - Measurement errors when estimating the vertical jump height with flight time
using photocell devices: the example of Optojump.
AB - Common methods to estimate vertical jump height (VJH) are based on the
measurements of flight time (FT) or vertical reaction force. This study aimed to
assess the measurement errors when estimating the VJH with flight time using
photocell devices in comparison with the gold standard jump height measured by a
force plate (FP). The second purpose was to determine the intrinsic reliability
of the Optojump photoelectric cells in estimating VJH. For this aim, 20 subjects
(age: 22.50+/-1.24 years) performed maximal vertical jumps in three modalities in
randomized order: the squat jump (SJ), counter-movement jump (CMJ), and CMJ with
arm swing (CMJarm). Each trial was simultaneously recorded by the FP and Optojump
devices. High intra-class correlation coefficients (ICCs) for validity (0.98
0.99) and low limits of agreement (less than 1.4 cm) were found; even a
systematic difference in jump height was consistently observed between FT and
double integration of force methods (-31% to -27%; p<0.001) and a large effect
size (Cohen's d>1.2). Intra-session reliability of Optojump was excellent, with
ICCs ranging from 0.98 to 0.99, low coefficients of variation (3.98%), and low
standard errors of measurement (0.8 cm). It was concluded that there was a high
correlation between the two methods to estimate the vertical jump height, but the
FT method cannot replace the gold standard, due to the large systematic bias.
According to our results, the equations of each of the three jump modalities were
presented in order to obtain a better estimation of the jump height.
PMID- 28416901
TI - Mechanical efficiency in children with different body weight: a longitudinal
assessment of the quality cohort.
AB - Net mechanical efficiency (MEnet), which reflects the body's ability to transfer
energy above resting levels in external work, is similar in young children
regardless of their body weights. However, it is unclear whether MEnet remains
stable during growth and maturation. We sought to determine whether net
mechanical efficiency (MEnet) changes over a period of 3 years in children and to
identify the factors associated with possible changes. A total of 169 children
participating in the QUALITY (Quebec Adipose and Lifestyle InvesTigation in
Youth) cohort completed an incremental cycling test, resulting in the same
maximal power output during both visits. For MEnet, resting energy consumption
was subtracted from total energy consumption at each exercise stage. Physical
activity was measured using an accelerometer worn for 7 days. Participants were
measured at year one and again two years later. MEnet did not differ across the
visits at the 25, 50 and 75 watt stages. However, the participants exhibited
lower MEnet values at follow-up for the 100 and 125 W stages (23(3) vs. 20(1)%;
25(4) vs. 20(2)%; p<0.01). Declines in MEnet correlated positively with declines
in moderate-to-vigorous physical activity levels (r=0.78, p<0.05). The declines
in moderate-to-vigorous physical activity levels across the visits were
identified as significant predictors of MEnet changes at 100 and 125 W over 3
years, accounting for 22% of the relationship. In children, MEnet, determined at
high exercise intensity, decreases within a period of three years, and the
decrement appeared to be related to moderate-to-vigorous physical activity.
PMID- 28416902
TI - A first look into the influence of triathlon wetsuit on resting blood pressure
and heart rate variability.
AB - The purpose of this study was to investigate the effects of wearing a wetsuit on
resting cardiovascular measures (blood pressure (BP), heart rate variability
(HRV)). The influence of position (upright, prone) and wetsuit size were also
explored. Participants (n=12 males, 33.3+/-12.1 years) had BP and HRV measured
during six resting conditions: standing or prone while not wearing a wetsuit
(NWS), wearing the smallest (SWS), or largest (LWS) wetsuit (based upon
manufacturer guidelines). Heart rate was recorded continuously over 5-mins; BP
was measured three times per condition. HRV was represented by the ratio of low
(LF) and high (HF) frequency (LF/HF ratio); mean arterial pressure (MAP) was
calculated. Each dependent variable was analyzed using a 2 (position) x 3
(wetsuit) repeated measures ANOVA (alpha=0.05). Neither HRV parameter was
influenced by position x wetsuit condition interaction (p>0.05) and MAP was not
influenced by position (p=0.717). MAP and LF/HF ratio were both influenced by
wetsuit condition (p<0.05) with higher during SWS than NWS (p=0.026) while LF/HF
ratio was lower during SWS compared to NWS (p=0.032). LF/HF ratio was influenced
by position being greater during standing vs. prone (p=0.001). It was concluded
that during resting while on land (i.e., not submerged in water), wearing a
small, tight-fitting wetsuit subtlety altered cardiovascular parameters for
healthy, normotensive subjects.
PMID- 28416903
TI - Effects of strength training with blood flow restriction on torque, muscle
activation and local muscular endurance in healthy subjects.
AB - The present study aimed to analyse the effects of six weeks of strength training
(ST), with and without blood flow restriction (BFR), on torque, muscle
activation, and local muscular endurance (LME) of the knee extensors. Thirty
seven healthy young individuals were divided into four groups: high intensity
(HI), low intensity with BFR (LI+BFR), high intensity and low intensity + BFR
(COMB), and low intensity (LI). Torque, muscle activation and LME were evaluated
before the test and at the 2nd, 4th and 6th weeks after exercise. All groups had
increased torque, muscle activation and LME (p<0.05) after the intervention, but
the effect size and magnitude were greater in the HI, LI+BFR and COMB groups. In
conclusion, the groups with BFR (LI+BFR and COMB) produced magnitudes of muscle
activation, torque and LME similar to those of the HI group.
PMID- 28416904
TI - Estimating life expectancy of the population in Cyprus with the use of life
tables.
AB - AIM: The aim of this study was to investigate the life expectancy of the Cypriot
population between 1986 and 2012. MATERIAL AND METHODS: We used the data reported
in the annual editions of the Statistical Service of Cyprus and constructed life
tables of the Cypriot population between 1986 and 2012. RESULTS: For both
genders, and for males and females separately, in the year 1986 life expectancy
accounted 74.47, 72.2, and 76.76 years respectively, while in 2012 values
increased to about 81.28, 79.02, and 83.50 years respectively. The longitudinal
trend of life expectancy is to increase over the calendar years. The largest
increase in life expectancy occurred at birth and was approximately seven years
for both males and females. Until the age of 55, this gain was approximately six
years of life. From age 60 to 65 years, the gain was about five years of life,
and in the oldest age groups, the gain was four years of life. The values
corresponding to male were lower compared to those corresponding to females, with
the exception of the age 0 (at birth). CONCLUSIONS: A significant increase in
life expectancy of the Cypriot population was noted in the period 1986-2012,
which was more obvious at younger ages and in females. Hippokratia 2016, 20(2):
99-103.
PMID- 28416905
TI - Transitory evoked otoacoustic emission (TEOAE) and distortion product otoacoustic
emission (DPOAE) outcomes from a three-stage newborn hearing screening protocol.
AB - OBJECTIVE: Comparison of the efficacy of Transitory Evoked Otoacoustic Emissions
(TEOAEs) and Distortion Product Otoacoustic Emissions (DPOAEs) in a neonatal
hearing screening protocol, based on a three-stage strategy. METHODS: In the
first stage, a hearing screening using both evoked emissions was conducted in
3,480 neonates from March 2006 through January 2012. Both TEOAEs and DPOAEs were
recorded. Neonates, who did not undergo the test before being discharged, were
examined within 30 days at a scheduled appointment. Follow-up of the referred
newborns (second-stage screening) was performed as an outpatient re-screening,
within a month. The third-stage evaluation, i.e., the diagnostic testing,
included a clinical otolaryngological examination, high-frequency tympanometry at
1,000 Hz and Auditory Brainstem Response (ABR) measurements. RESULTS: A total of
3,480 (97%) newborns (n =1,765 males) out of 3,595 infants were enrolled in the
study. In the first-stage evaluation, 8.9 % of the infants were referred
according to TEOAEs, while the percentage of the referred infants for
DPOmicronAlphaEpsilons was 25.7 %. At this initial assessment stage, the
specificity of TEOAES and DPOAEs were determined as 92% and 75%, while positive
predictive values (PPV) were 3.8 % and 1.3 %, respectively. In the second stage
of evaluation, the specificity of TEOAES and DPOAEs were 86 % and 76 %, while the
PPV increased to 18 % and 15 %, respectively. CONCLUSIONS: With a lower follow-up
rate, TEOAEs testing was significantly easier to perform and more reliable
compared to the DPOAEs test. Hippokratia 2016, 20(2): 104-109.
PMID- 28416906
TI - Metabolic syndrome in patients with chronic obstructive pulmonary disease:
frequency and relationship with systemic inflammation.
AB - BACKGROUND: Metabolic syndrome (MetS) is frequent in patients with chronic
obstructive pulmonary disease (COPD). Systemic inflammation plays an important
role in both COPD and MetS. The aim of this study was to assess the frequency of
MetS in COPD patients and to evaluate the status of systemic inflammation in COPD
patients with MetS and those without MetS. METHODS: This cross-sectional study
included 98 consecutive stable COPD patients. The MetS was defined using the
criteria of the International Diabetes Federation. Components of MetS and markers
of systemic inflammation: C-reactive protein (CRP), fibrinogen, and leukocyte
count were measured. All patients underwent spirometry. The staging of COPD was
made according to the Global initiative for chronic obstructive lung disease
(GOLD) criteria. RESULTS: MetS was present in 37.8 % COPD patients. The
frequencies of MetS in patients with GOLD stages I, II, III, and IV were 33.3 %,
48.8 %, 31.6 %, and 23.1 %, respectively. MetS frequencies were not significantly
different between GOLD stages. The multivariate logistic regression analysis
revealed leukocyte count and CRP level as significant independent predictors of
the presence of Mets in COPD patients (OR =1.321, 95%CI: 1.007-1.628, p =0.009
and OR =1.184, 95%CI: 1.020-1.376, p =0.027 respectively). CONCLUSIONS: This
study shows that MetS is frequent in patients with COPD. Systemic inflammatory
markers are higher in COPD patients with MetS than in patients without MetS.
These findings suggest that physicians should screen COPD patients for associated
MetS and elevated circulatory inflammatory markers. Management of these disorders
should reduce the risk of cardiovascular morbidity and mortality in these
patients. Hippokratia 2016, 20(2):110-114.
PMID- 28416907
TI - Self-reported autonomic symptoms in Parkinson's disease: properties of the SCOPA
AUT scale.
AB - BACKGROUND AND AIM: Autonomic symptoms in Parkinson's disease (PD) are very
common and contribute to the severity of patient's disability. We evaluated the
occurrence of autonomic symptoms in Greek patients with PD utilizing the Scales
for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT), a
specific 23-item self-completed questionnaire for the assessment of autonomic
dysfunction in patients with PD. SUBJECTS AND METHODS: One hundred and sixty-one
PD patients and forty matched controls were enrolled in the study. Clinical
assessment was performed with the Hoehn and Yahr scale. Patients completed a
demographic questionnaire, the Non-Motor Symptoms Questionnaire (NMSQuest), the
Parkinson's Disease Questionnaire (PDQ-39) and the SCOPA-AUT scale which was
properly translated into Greek and validated for the study. RESULTS: SCOPA-AUT
scale showed a good reliability profile and correlated well with other measures
for non-motor symptoms and health-related quality measures in PD patients. PD
patients scored higher than controls in the total SCOPA -AUT score (mean score
11.9 versus 6.4). Patients reported problems in many items of the SCOPA-AUT, but
the most common autonomic symptoms emerged in the Urinary and the
Gastrointestinal domains. Especially sialorrhea, constipation, straining for
defecation, incontinence and nocturia differentiated patients from controls.
Furthermore, mean total SCOPA-AUT score correlated with duration and severity of
the disease. CONCLUSION: Autonomic symptoms in PD are too important to remain
undetected. By incorporating into everyday practice the use of suitable and
reliable questionnaires, physicians will be able to adequately detect and manage
these symptoms. Hippokratia 2016, 20(2):115-120.
PMID- 28416909
TI - Factors predicting a positive capsule endoscopy in past overt obscure
gastrointestinal bleeding: a multicenter retrospective study.
AB - OBJECTIVES: Capsule endoscopy (CE) remains the examination of choice for the
investigation of obscure gastrointestinal bleeding. Although the factors
predicting positive CE findings in the overall obscure gastrointestinal bleeding
have been investigated, the clinical characteristics that predict a positive CE
in patients with past overt obscure gastrointestinal bleeding (OOGIB) have not
been systematically studied. METHODS: Between September 2004 and December 2013,
262 patients underwent CE for evaluation of past OOGIB after negative upper and
lower endoscopy, and other diagnostic modalities. Patients' records were
retrospectively reviewed to assess the factors that could possibly predict
positive CE findings. RESULTS: Two hundred and twenty four patients with a median
age of 70 years (range: 17-87) were enrolled in the final analysis and were
divided into two groups; those who had positive (group A: 118 patients) and those
who had negative CE findings (group B: 106 patients). The overall diagnostic
yield of CE was 52.68 %. Multivariate analysis demonstrated that age >65 years,
anticoagulant use, antiplatelet use, and non-steroidal anti-inflammatory drugs
use were independent predictive factors for positive findings on CE. Of the 118
patients with positive CE, therapeutic interventions were performed in 56
patients (47.46 %). Recurrence of bleeding presented in nine patients of group B
compared with 39 patients of group A (p <0.001). CONCLUSIONS: Certain clinical
characteristics predict a positive CE in patients with past OOGIB. Patients with
OOGIB and negative CE had a considerably lower rebleeding rate, and further
invasive investigational procedures may be adjourned or may not be required,
though such recommendation warrants further validation. Hippokratia 2016, 20(2):
127-132.
PMID- 28416908
TI - Incidence and factors predisposing to retinopathy of prematurity in inborn
infants less than 32 weeks of gestation.
AB - PURPOSE: Retinopathy of prematurity (ROP) is a visual-impairing disorder of the
developing retinal vasculature in premature infants. Recent advances in neonatal
care have led to an increase in the vulnerable premature population. The aim of
this retrospective study was to assess the incidence of ROP and its risk factors
according to degree of prematurity. METHODS: Data from a sequence of 1,562
infants <32 weeks of gestational age, admitted to the Jewish General Hospital
Neonatal Intensive Care Unit, a tertiary care perinatal center in Montreal,
Canada, were reviewed to determine the incidence and risk factors of ROP.
Perinatal risk factors for ROP were analyzed using univariate and multivariate
analyses in four consecutive gestational age (GA) groups (24-25+6/7weeks, 26
27+6/7 weeks, 28-29+6/7 weeks and 30-31+6/7 weeks). RESULTS: The overall
incidence in our study was 15.6 %. Severe ROP, defined as stage 3 or plus disease
was detected in 5.2 % of the neonates screened. In the univariate analyses, many
risk factors in each GA group were found to have a significant association with
ROP. On subsequent multivariate logistic regression analysis, birth weight, small
for gestational age, the presence of patent ductus arteriosus (PDA), sepsis,
necrotizing enterocolitis (NEC), and mechanical ventilation >7 days were
independently associated with the development of ROP. Birth weight was
consistently an independent risk factor for ROP in all GA groups. CONCLUSION: Our
study confirmed the importance of birth weight as an independent ROP risk factor.
Sepsis, NEC, PDA, and prolonged mechanical ventilation have been shown to be
independent risk factors in the different gestational age groups. Hippokratia
2016, 20(2): 121-126.
PMID- 28416910
TI - The role of serum osteoprotegerine in metastatic prostate cancer - a case control
study.
AB - INTRODUCTION: Prostate cancer is one of the most common malignant neoplastic
diseases in men. Early control of the disease progression contributes
significantly to survival rates and patients' quality of life. Osteoprotegerin is
a dimeric glycoprotein, which affects bone metabolism and inhibits
osteoclastogenesis. In the present study, we evaluated the expression of
osteoprotegerin in the serum of prostate cancer patients with or without skeletal
metastases. METHODS: The expression of serum osteoprotegerin, as measured by
enzyme-linked immunosorbent assay, has been studied in 82 patients with locally
controlled prostate cancer, in 49 patients with metastatic bone disease and in a
control group of 41 healthy males. At sampling time 65/131 of included patients
were newly diagnosed, while 66/131 patients were already under hormonal therapy.
All eligible prostate cancer patients had histologically confirmed malignancy.
Serum total prostate-specific antigen (PSA) was determined by an
immunoradiometric assay. We investigated the expression of osteoprotegerin in
hormone-dependent and hormone-refractory prostate cancer and its relation to
disease progression. RESULTS: Among the 131 patients with prostate cancer, higher
osteoprotegerin and PSA concentrations have been observed in metastatic bone
patients' sera (p <0.001). ROC analysis between the metastatic and locally
controlled prostate cancer patients has shown a statistically significant area
curve (p <0.001) and a cut-off limit of 89.6 pg/ml. Moreover, 15.3 % of patients
became hormone-resistant, with osteoprotegerin values significantly increased
compared with hormone-sensitive prostate cancer patients (p <0.001). CONCLUSIONS:
It seems that elevated levels of serum osteoprotegerin in patients with prostate
cancer reflect the bone metastatic extent and may potentially be used in
metastatic patients' follow-ups. Hippokratia 2016, 20(2): 133-138.
PMID- 28416911
TI - Quality of life of patients with advanced cancer treated in a regional hospital
in Greece.
AB - BACKGROUND: Quality of life (QoL) assessment contributes to the better care of
cancer patients. The aim of the study was to determine QoL among treated patients
with advanced cancer (ACPs) in the island of Crete, Greece, their satisfaction
with the given care and to evaluate possible differences in QoL between in- and
day care clinic patients. METHODS: The QoL of 95 Greek ACPs with breast, lung,
and colon cancer were evaluated using the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3), and
its Breast (QLQ-BR23) and Lung (QLQ-LC13) Cancer modules, while their
satisfaction with the given care was evaluated with a 10-point questionnaire.
Multiple linear regression analysis was used to assess associations of QoL with
patients' demographic and clinical characteristics. RESULTS: Patients reported
moderate global health status/QoL (62.6) and higher cognitive, physical, and
emotional scores (75.4, 66.8, and 66.6 respectively). In symptoms scales/items,
all patients had mean scores <50 while higher mean scores were observed for
fatigue (41.8) and dyspnea (36.2). No significant differences in functioning and
symptoms scales were found between different cancer types. Sexual functioning in
QLQ-BR23 and alopecia in QLQ-LC13 severely affected QoL. Hospitalized patients
reported worse mean global QoL than those visiting the day care clinic (55.6
versus 67.6, p =0.017), as well as in all parameters described by QLQ-C30. Most
patients were satisfied with the given care (>=8/10, 74.2% of patients).
CONCLUSIONS: ACPs in the present study were found to have an overall good QoL,
functioning, and symptoms scores and were satisfied with the given care. Fatigue,
dyspnea, alopecia, and sexual dysfunction were found to be among the most
frequently reported distressing symptoms. Hippokratia 2016, 20(2): 139-145.
PMID- 28416912
TI - Evaluation of malnutrition detected with the Nutritional Risk Screening 2002 (NRS
2002) and the quality of life in hospitalized patients with chronic obstructive
pulmonary disease.
AB - BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD)
have impaired quality of life, but the relationship between their nutritional
status and quality of life has not been established. The aim of this study was to
determine the relationship between quality of life and nutritional status in
hospitalized COPD patients. METHODS: Demographic data, quality of life and
nutritional status of 90 inpatients with a mean age of 68.76 +/- 10.85 years were
enrolled in the study. The Nutritional Risk Screening 2002 (NRS-2002) tool was
used to evaluate their nutritional status. The quality of life was assessed using
the Short Form-36 (SF-36) questionnaire. The correlation analysis was used for
the relationship between SF-36 subscales and nutritional status variables.
RESULTS: Of the 90 COPD patients included in the study, 54.4 % were men, and 45.6
% were women. Moderate, severe, and very severe COPD were detected in 37.8 %,
38.9 %, and 23.3 % of the patients, respectively. At risk of malnutrition were
55.6 % of the 90 COPD patients, whereas 44.4 % were not. The scores for physical
function, physical role functioning, pain, general health, emotional role
functioning, vitality, social function, and mental function subscales were lower
in the patients at risk of malnutrition (p <0.001). There was a statistically
significant negative correlation between malnutrition score and the subscores of
SF-36 related to physical function, physical role functioning, pain, general
health, emotional role functioning, vitality, social function, and mental
function (p <0.001). CONCLUSIONS: COPD patients were found to have a high risk of
malnutrition that adversely affects their quality of life. Therefore, the
evaluation of the nutritional status of COPD patients should be an integral part
of their clinical treatment plans aiming towards improving their quality of life.
Hippokratia 2016, 20(2):147-152.
PMID- 28416913
TI - Long-term response in biochemical markers of bone turnover during enzyme
replacement therapy in a case-series of patients with Gaucher disease type I from
Northern Greece.
AB - BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder characterized by
severe skeletal complications. Bone complications are an important cause of
morbidity of GD and are thought to result from imbalance in bone remodeling. The
objective of this case series was to analyze the long-term effect of enzyme
replacement therapy on chemokines MIP-1a and MIP-1b, cytokines IL-3, IL-6, IL-10,
and IL-12, osteoprotegerin (OPG) and osteocalcin (BGP), chitotriosidase,
quantitative ultrasound sonography (QUS), bone magnetic resonance imaging (MRI)
and dual-energy X-ray absorptiometry (DXA) in patients with GD in Northern
Greece. In addition, the study aimed in investigating possible relationship
between the above mentioned parameters. PATIENTS AND METHODS: Seven patients with
GD type I (three males and four females) were included in the study. Mean age was
26.29 +/- 15.34 years (range 7-47 years). Six patients were receiving enzyme
replacement therapy (ERT), with 40-60 IU/kg of imiglucerase weekly, for a mean
period of 36 months prior to study initiation. One patient started ERT after his
inclusion in the study. The levels of MIP-1a, MIP-1b, IL-3, IL-6, IL-10, IL-12,
OPG, BGP, chitotriosidase, bone imaging parameters assessed with two different
techniques (QUS and DXA) and MRI data were estimated at baseline (T0) and after
two years on ERT. RESULTS: Chitotriosidase, MIP-1a, and IL-6 levels decreased in
all patients after two years of ERT (p =0.05). In contrast, OPG and BGP levels
increased (p =0.04 and p =0.02, respectively). Bone mineral density (BMD)
demonstrated a progressive improvement with regards to the Z-score in all
patients (p =0.05). The decrease in the plasma levels of MIP-1a strongly
correlated with a decrease in the plasma levels of chitotriosidase. Additionally,
decreased plasma levels of IL-6 were correlated with increased Z-score both at
baseline (T0) as well as two years later, in all patients. There was no
correlation between MRI findings and any inflammatory biomarker. CONCLUSIONS:
Measurement of serum markers in patients with GD under ERT could be used as an
auxiliary tool in the monitoring of bone involvement, in combination with MRI
imaging and BMD. However, larger studies involving higher numbers of GD patients
are needed to confirm these conclusions. Hippokratia 2016, 20(2): 153-159.
PMID- 28416914
TI - Atrial fibrillation causing ST elevation myocardial infarction due to coronary
embolism: case report and review of the literature.
AB - BACKGROUND: Atrial fibrillation is a rare but important nonatherosclerotic cause
of ST elevation myocardial infarction. CASE DESCRIPTION: We report the case of a
69 years old woman who presented to our hospital with ST elevation myocardial
infarction and permanent atrial fibrillation and eventually treated with thrombus
aspiration from the left descending coronary artery. CONCLUSION: We have to
notice the importance of the appropriate antithrombotic treatment in atrial
fibrillation to prevent systemic embolism. In selected cases with ST elevation
myocardial infarction due to coronary embolism, aspiration thrombectomy with or
without balloon dilatation or stenting can be safely performed. Hippokratia 2016,
20(2):160-162.
PMID- 28416915
TI - Hypokalemia-induced cardiac arrest in a Duchenne muscular dystrophy patient.
AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive myopathic
disorder, inherited as X-linked recessive traits, in which muscle weakness is the
primary symptom. Correlation between DMD and hypokalemia is reported in only
three case reports. Recent investigations have focused on the nutritional
management of patients with DMD. However, there are no data regarding
recommendations on potassium intake. Description of case: We report the case of a
15-year-old male patient with DMD, who developed sudden cardiac arrest following
severe hypokalemia (K: 1.3 mEq/L) during a lower respiratory tract infection.
Hypokalemia was gradually corrected with intravenous potassium chloride. The
patient, after a prolonged hospitalization due to hypoxic encephalopathy, was
discharged from the Intensive Care Unit (ICU) on mechanical ventilation.
CONCLUSION: Severe hypokalemia is a rare complication of DMD, with potentially
lethal consequences. Therefore, in patients with DMD, potassium levels should be
closely monitored and adjusted with appropriate diet or potassium supplements as
needed. Hippokratia 2016, 20(2): 163-165.
PMID- 28416916
TI - Concentration-related mydriasis in a patient with renal dysfunction treated with
phenytoin.
AB - INTRODUCTION: There is very limited evidence concerning phenytoin-related
mydriasis. CASE REPORT: A 59-year-old male was hospitalized in the intensive care
unit due to a head injury. During his hospitalization, phenytoin was
administrated. Some days later he presented bilateral mydriasis. At that time he
had impaired creatinine clearance 7 ml/min, albumin levels 3.4 gr/dl, and
phenytoin serum concentration 19.94 MUg/dl. Evaluation with brain computed
tomography and magnetic resonance imaging did not reveal any potential cause of
mydriasis, while none of the co-administrated drugs have been reported to cause
significant mydriasis. After initiation of continuous venovenous
hemodiafiltration and discontinuation of phenytoin, mydriasis was reversed.
CONCLUSION: Clinicians should be aware that mydriasis due to a toxic
concentration of phenytoin may be manifested. Hippokratia 2016, 20(2): 166-168.
PMID- 28416917
TI - Laparoscopic microwave ablation for the management of hemorrhage from ruptured
hepatocellular carcinoma.
AB - BACKGROUND: Treatment of ruptured hepatocellular carcinoma (HCC) focuses on
hemorrhage control and utilizes tumor vascular anatomy to palliate or temporize
selected patients with hepatic artery embolization (HAE). Radiofrequency ablation
(RFA) and microwave ablation (MWA) are feasible alternatives or adjunct
modalities to resection of HCC; the method of energy delivery in MWA allows
uniform coagulative necrosis in shorter time compared with RFA. CASE DESCRIPTION:
We present the case of an 82-year-old man who presented with a ruptured liver
tumor with active intraperitoneal bleeding on angiography. The patient remained
hemodynamically stable with evidence of ongoing bleeding following HAE. Tumor
destruction and definitive hemostasis were obtained with minimally invasive MWA.
CONCLUSION: Tumor rupture remains a negative prognostic factor in the course of
HCC. In select patients, MWA allows definitive hemorrhage control with minimal
surgical morbidity. Hippokratia 2016, 20(2): 169-171.
PMID- 28416918
TI - Selective rehabilitation of peripheral facial palsy for idiopathic and traumatic
palsy.
PMID- 28416919
TI - Lipemia and acute coronary syndrome: when color enlightens the truth.
PMID- 28416920
TI - Interleukin 6 as a potential diagnostic and prognostic biomarker in saliva in
patients with carcinoma of the larynx.
PMID- 28416921
TI - Laparoscopic diagnosis of abdominal tuberculosis.
PMID- 28416922
TI - Prevalence of paraoxonase-1 polymorphisms in diabetes mellitus type 2 Greek
patients.
PMID- 28416923
TI - Esophageal Achalasia: Predictive Value of Preoperative Resting Pressure of LES
Correlated with Type of Fundoplication.
AB - OBJECTIVE: The aim of the present study is to show the predictive value of the
preoperative resting pressure of the lower esophageal sphincter (LES) correlated
with the type of fundoplication (Nissen or Dor) after Heller myotomy in our
series. MATERIALS AND METHODS: From January 1998 to June 2010, 88 patients
affected by esophageal achalasia underwent surgery at our unit. However, our
study focused on a sample of 36 patients, because many data were lost or was
never recorded. Among these, 14 patients underwent laparoscopic Heller myotomy
plus Nissen fundoplication (group N), whereas 22 patients underwent laparoscopic
Heller myotomy plus Dor fundoplication (group D). Clinical evaluation was
performed using a modified DeMeester symptom scoring system consisting of the
assessment of three symptoms: dysphagia, regurgitation, and heartburn. To each
symptom was assigned a score from 0 to 3, depending on its severity, and the
reduction in the severity of each symptom after surgery was assessed. RESULTS:
The surgical treatment is considered to be effective (p<0.0001). The preoperative
resting pressures of LES were compared by Student's t-test, and it was found that
patients who reported a greater improvement in the dysphagia symptom had a
preoperative average pressure of LES that was significantly higher than that in
other patients in both group N (p=0.03) and group D (p=0.01; p=0.003; p=0.001).
The Dor treatment was shown to be more effective than the Nissen treatment
(p<0.0001). CONCLUSION: The preoperative resting pressure of LES is a predictive
factor of surgical success both before Dor fundoplication and before Nissen
fundoplication, but its predictive power is influenced by the chosen type of
fundoplication.
PMID- 28416924
TI - Comparison of Second and Third-Generation Nails in the Treatment of
Intertrochanteric Fracture: Screws versus Helical Blades.
AB - OBJECTIVE: The aim of this study was to compare the radiological and functional
outcomes of anti-rotation trochanteric nails (ATNs) with proximal femoral nail
anti-rotation (PFNA) in the treatment of intertrochanteric femur fractures in
elderly patients. MATERIALS AND METHODS: In total, 165 intertrochanteric
fractures were treated between January 2007 and January 2010. One hundred forty
patients were included. The operation time, amount of blood loss, fluoroscopy
screening time, and length of hospitalization were recorded. The radiological
position of the implant, quality of fracture reduction, and tip-apex distance
were evaluated, and the postoperative complications as well as functional
condition of the patients were assessed. RESULTS: There were no significant
differences between the ATN and PFNA groups for the presence of general
complications, length of hospitalization, and functional capacity. The mean
operation time, blood loss amount, and fluoroscopy screening time were more in
the ATN group than in the PFNA group. Reoperation was needed for nine and two
patients in the ATN and PFNA groups, respectively, because of implant-related
complications. CONCLUSION: Both ATNs and PFNA were suitable for the fixation of
intertrochanteric fractures, but the risk of complication occurrence and need for
reoperation were found to be higher in patients who were treated with ATNs.
PMID- 28416925
TI - Shear Wave Sonoelastography Findings of Testicles in Chronic Kidney Disease
Patients Who Undergo Hemodialysis.
AB - OBJECTIVE: Chronic kidney disease (CKD) is known to cause significant
deterioration in the function of the testicles and sexual dysfunction in male
patients who undergo hemodialysis. The aim of this study was to show the changes
in the testicles that occur as a result of hypogonadism secondary to CKD and to
analyze the elasticity of the parenchyma by shear wave sonoelastography.
MATERIALS AND METHODS: In our study we included 28 male patients who undergo
dialysis three times per week and 25 healthy volunteers. Firstly, B-mode
ultrasonographic evaluation was performed in both testicles for structural
analysis and to detect the presence of focal lesions. Afterward, the stiffness of
the parenchyma was measured in kilopascals by shear wave sonoelastography.
RESULTS: The CKD group had lower right, left, and mean testicular volumes
(p<0.001). The CKD group also displayed greater right, left, and mean testicular
parenchymal stiffness (p<0.001). CONCLUSION: CKD patients who undergo
hemodialysis demonstrated significant changes in testicular size and stiffness in
comparison to healthy volunteers.
PMID- 28416926
TI - The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on
the Contractions of Rat Thoracic Aorta.
AB - OBJECTIVE: It was suggested that prostaglandins which are synthesized by
cyclooxygenase (COX) enzymes contribute to the actions of angiotensin-converting
enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism and there is an
interaction between ACE signaling pathway and COX enzymes. We aim to investigate
the role of COX enzymes in the effects of losartan, an angiotensin II (Ang II)
receptor antagonist or lisinopril, an ACE inhibitor, on the contractions of rat
thoracic aorta in isolated tissue bath. MATERIALS AND METHODS: Responses of
losartan (10-6, 10-5, 10-4 M), lisinopril (10-6, 10-5, 10-4 M), and non-selective
COX inhibitor dipyrone (10-4, 7 * 10-4, 2 * 10-3 M) alone to the contractions
induced by phenylephrine (Phe) (10-7 M), potassium chloride (KCl) (6 * 10-2 M),
Ang II (10-8 M) and responses of losartan or lisinopril in combination with
dipyrone to the contractions induced by Phe or KCl were recorded. RESULTS: When
used alone, dipyrone and losartan inhibited Phe, KCl, and Ang II-induced
contractions, whereas lisinopril inhibited only Phe and Ang II-induced
contractions. Inhibition of COX enzymes (COX-3, COX-3 + COX-1, COX-1+ COX-2 + COX
3 by dipyrone 10-4, 7 * 10-4, 2 * 10-3 M, respectively) augmented the relaxant
effects of losartan or lisinopril. Also, dipyrone potentiated the effect of
lisinopril on KCl-induced contractions. CONCLUSION: We suggest that dipyrone
increases the smooth-muscle relaxing effects of losartan or lisinopril and that
COX enzyme inhibition may have a role in the enhancement of this relaxation.
PMID- 28416927
TI - Cataract Surgery and Possible Complications in Patients with Pseudoexfoliation
Syndrome.
AB - OBJECTIVE: The aim of this study was to evaluate the demographic characteristics
and intraoperative complications of cataract surgery in patients with
pseudoexfoliation syndrome (PEX). MATERIALS AND METHODS: Cases of 225 eyes (80
eyes with pseudoexfoliation and 145 eyes without pseudoexfoliation as the control
group) that underwent phacoemulsification cataract surgery and IOL implantation
at the Silifke State Hospital Ophthalmology Clinic between April 2011 and April
2013 were analysed retrospectively. Patients with a history of previous ocular
surgeries, ocular trauma, uveitis, glaucoma or corneal pathology were not
included in the study. All cataract procedures were performed by the same
surgeon. Patients' age, gender, anterior segment and fundus findings in both
eyes, presence of pseudoexfoliative material, pre- and postoperative day 1
intraocular pressure (IOP) and surgery notes were evaluated. RESULTS: There were
51 (34.7%) males and 29 (38.6%) females among the PEX cataract patients, and 98
(65.3%) male and 47 (61.8%) female controls. The incidence of pseudoexfoliation
was similar in women (38.2%) and men (34.7%) (p=0.660). The mean age was 74.64+/
6.8 in the PEX group and 68.95+/-7.5 in the control group. Mean age was
significantly higher in the PEX group compared to controls (p<0.001). Poor pupil
dilation occurred intra-operatively in 60 (75%) of the patients with
pseudoexfoliation and in 17 (11.7%) of the control patients. Frequency of poor
intraoperative pupil dilation was significantly higher in the PEX group
(p<0.001). Intraoperative vitreous loss occurred in 7 (8.8%) PEX patients and 5
(3.4%) controls, but this difference was statistically insignificant (p=0.090).
CONCLUSION: Surgeons should be aware of the potential complications of cataract
procedures in patients with PEX. Caution should be taken at every stage of the
surgery to prevent these complications, and surgeons should be knowledgeable and
skilful in complication management should they arise.
PMID- 28416928
TI - Comparison of Anesthetic Administration According to Method of Hip Surgery.
AB - OBJECTIVE: The aim of this study is to compare total hip prosthesis (THP),
partial hip prosthesis (PHP), and proximal femoral nail (PFN) patients in terms
of the chosen anesthetic method. METHODS: A total of 850 patients who underwent
hip surgery were divided into 3 groups according to the operation type: PHP
(n=281), PFN (n=393), and THP (n=176). The type of anesthesia administered,
interventions during anesthesia, and complications were retrospectively
evaluated. The groups were compared in terms of patient age, American Society of
Anesthesiologists (ASA) scores, chosen anesthetic method, operation duration,
colloid use during operation, use of antihypertensive medication, use of
vasoconstrictor medication, development of hypotension, blood transfusion
administered, development of cardiac arrest, requirements for intensive care
after operation, and use of a central catheter. RESULTS: In the THP group, the
mean age of patients was significantly lower as compared to the PHP and PFN
groups. The duration of operation was lower in the PFN group as compared to the
other two groups. In the THP group, general anesthesia was significantly high,
while in the PFN group, regional anesthetic administration was high. While
colloid use was greater in the PFN group, the blood transfusion rate was higher
in the THP group. The use of antihypertensive medication was higher in the THP
group as compared to the other groups. CONCLUSION: Although all three anesthetic
methods could be used in hip surgery, the type of anesthesia should be chosen
according to the type of hip surgery considering the duration of operation, age
of the patient, and blood lost during the operation.
PMID- 28416929
TI - Role of Coma Acidosis Malaria Score in Patients with Severe Malaria among Indian
Population: a Tertiary Care Center Experience.
AB - OBJECTIVE: Malaria is a prime public health threat in developing countries like
India. There is an unmet need of a simplified methodology for the purpose of
triage and provision of intensive care to the severely infected patients in these
areas. MATERIALS AND METHODS: We did a prospective study in patients (n=60)
admitted with severe malaria in a single tertiary care center in the state of
Haryana, India. We assessed the role of coma acidosis malaria (CAM) score in
these patients when predicting mortality and morbidity events. Stepwise logistic
regression analysis was applied to identify patients requiring intensive care
based on the CAM score, and the prediction value of the scoring system was
assessed among these patients. RESULTS: Cerebral malaria (measured using the
Glasgow coma scale) and acidosis (base deficit) were the major determinants of
the CAM score. Serum bicarbonate levels and respiratory rates were assessed as
the proxy markers of the base deficit as it is not always available. Morbidity
increased steadily as the CAM scores increased. Sensitivity and negative
predictive value of 100% depicted that the scoring system was able to identify
patients who needed intensive care and accurately exclude the patients who could
be conservatively managed in the ward. Positive predictive values of 73.9%, 68%,
and 80.9% indicated that CAM, bicarbonate-based CAM (BCAM), and respiratory rate
based CAM (RCAM) scores, respectively, could precisely predict the morbidity and
mortality events among patients with CAM scores >=2. CONCLUSION: CAM scores have
precise predictive values in assessing patients with severe malaria. The scoring
system helps in accurate and systemic triage of patients, irrespective of
species, and directs the treating physicians toward vigilant treatment and
emergency care.
PMID- 28416930
TI - What are the Prevalence of Abdominal Aortic Aneurysm in Patients with Chronic
Obstructive Pulmonary Diseases and the Characteristics of These Patients?
AB - OBJECTIVE: To determine the prevalence of abdominal aortic aneurysm (AAA) in
patients with chronic obstructive pulmonary disease (COPD) and to assess the
characteristics of these patients. MATERIALS AND METHODS: Stable COPD patients
(age, >40 years) were included in the study between January 2014 and June 2014.
Patients with acute exacerbations and a previous lung resection were excluded.
Data regarding demographic characteristics were recorded. The modified Medical
Research Council (mMRC) dyspnea scale was used to assess the severity of
breathlessness. The COPD Assessment Test (CAT) was performed. Abdominal aortic
diameter was measured using abdominal ultrasonography (AUS), and AAA was
diagnosed as an aortic diameter of >=30 mm at the renal artery level. RESULTS: In
total, 82 patients were examined. AAA was detected in five (6.1%) patients.
Diabetes mellitus, hypertension, and coronary artery disease were present in four
patients with AAA. The average mMRC score was 3.2+/-0.4, and the mean CAT score
was 18.4+/-6.0. Aneurysmal diameter was >50 mm in four patients and 37 mm in one
patient. Statistically significant differences were found between patient with
AAA and those without AAA with respect to the mean abdominal aortic diameters at
the renal artery and iliac artery levels (p=0.012 and 0.002, respectively).
CONCLUSION: Our findings suggest that AAA is associated with COPD, with a
prevalence rate of 6.1%. AAA is usually asymptomatic until a clinical status of
rupture, which is associated with a higher mortality risk. Early diagnosis of AAA
is lifesaving. In COPD patients, AAA might be easily determined using AUS, which
is a noninvasive and relatively cheap procedure.
PMID- 28416931
TI - Does Neuropathic Pain Affect the Quality of Sleep?
AB - OBJECTIVE: We aimed to evaluate the quality of sleep (QoS) in patients with
neuropathic pain (NP) and to investigate the association between possible QoS
impairment and NP characteristics. MATERIALS AND METHODS: Patients with NP and
controls were examined. Age, sex, NP duration, NP cause (central, peripheral, or
mixed), and pain intensity (with a Likert-type scale and visual analog scale)
were recorded. NP was screened with Douleur Neuropathique 4 questions (DN4), and
QoS was evaluated using the Pittsburg Sleep Quality Index (PSQI). Mann-Whitney U
test and regression analysis were performed to evaluate the data. RESULTS:
Seventy patients with NP and 30 age- and sex-matched controls were included. The
mean age of the patients and controls were 45.04+/-10.21 years and 39.00+/-19.23
years, respectively. Significantly higher scores of sleep latency (p=0.002),
sleep duration (p=0.003), sleep efficiency (p=0.002), sleep disturbance
(p<0.000), daytime dysfunction (p=0.04), and PSQI total were observed in patients
with NP than in controls (p<0.000). In addition, 80% of patients with NP and 37 %
of controls were classified as having poor QoS (p<0.000). Female sex, pain
intensity, and NP duration were found to be factors related to having poor QoS in
patients with NP (p=0.026, p=0.006, and p<0.000, respectively). CONCLUSION: In
our study, 80% of patients with NP had poor QoS regardless of the NP cause.
Female sex, pain severity, and NP duration were found to be factors correlated
with poor QoS. Treatment strategies that target not only NP itself but also
better QoS may contribute to the overall success of management.
PMID- 28416932
TI - Assessment of Endometrial Sampling and Histopathological Results: Analysis of
4,247 Cases.
AB - OBJECTIVE: This study aimed to investigate the relationship between indications
and histopathological results in patients undergoing endometrial sampling.
MATERIALS AND METHODS: Data of 4,247 patients undergoing endometrial sampling due
to non-obstetric gynecological causes between January 2010 and October 2016 were
retrospectively evaluated using the archives of the Gynecology and Obstetrics
Clinic of Konya Training and Research Hospital. RESULTS: The mean age of patients
was 46.8 +/- 8.22 years; the most common indication was
menometrorrhagia/menorrhagia (70.66%), and the least common indication was
cervical polyp (1.34%). The most common histopathological result was
proliferative-secretory endometrium (63.62%); simple hyperplasia with atypia
(0.56%) was determined to be the least common result. Endometrial cancer was
observed more frequently in the post-menopausal bleeding and increased
endometrial thickness group (23.11%). Of patients in whom biopsy was performed,
52.18% had undergone hysterectomy, as a result of which proliferative-secretory
endometrium was most commonly (59.52%) and simple hyperplasia with atypia least
commonly found as the histopathological diagnosis. CONCLUSION: Although sampling
should be performed following endometrial evaluation in patients with post
menopausal bleeding or increased endometrial thickness, according to the results
of our study, routine endometrial biopsy should not be preferred in the other
indications.
PMID- 28416933
TI - Thymectomy in Myasthenia Gravis.
AB - In recent years, thymectomy has become a widespread procedure in the treatment of
myasthenia gravis (MG). Likelihood of remission was highest in preoperative mild
disease classification (Osserman classification 1, 2A). In absence of thymoma or
hyperplasia, there was no relationship between age and gender in remission with
thymectomy. In MG treatment, randomized trials that compare conservative
treatment with thymectomy have started, recently. As with non-randomized trials,
remission with thymectomy in MG treatment was better than conservative treatment
with only medication. There are four major methods for the surgical approach:
transcervical, minimally invasive, transsternal, and combined transcervical
transsternal thymectomy. Transsternal approach with thymectomy is the accepted
standard surgical approach for many years. In recent years, the incidence of
thymectomy has been increasing with minimally invasive techniques using
thoracoscopic and robotic methods. There are not any randomized, controlled
studies which are comparing surgical techniques. However, when comparing non
randomized trials, it is seen that minimally invasive thymectomy approaches give
similar results to more aggressive approaches.
PMID- 28416935
TI - Juvenile Cystic Adenomyoma Mimicking a Uterine Anomaly: a Report of Two Cases.
AB - Juvenile cystic adenomyoma is a rare form of adenomyosis and described as a new
type of mullerian anomaly in literature. We are presenting two cases of juvenile
cystic adenomyoma which were misdiagnosed preoperatively as unicornuate uterus
with haematometra in a non-communicating rudimentary horn. The mainstay of
treatment is complete resection of lesion.
PMID- 28416934
TI - Sepsis and Septic Shock: Current Treatment Strategies and New Approaches.
AB - Sepsis is a complex condition characterized by the simultaneous activation of
inflammation and coagulation in response to microbial insult. These events
manifest as systemic inflammatory response syndrome or sepsis symptoms through
the release of proinflammatory cytokines, procoagulants, and adhesion molecules
from immune cells and/or damaged endothelium. Today, sepsis is a severe
multisystem disease with difficult treatments for its manifestations and high
mortality rates. In the last two decades in particular, many studies have been
conducted on sepsis that cause shock, multiorgan dysfunction, and organ failure
by especially leading to hemodynamic changes. In sepsis, increasing antibiotic
resistance and medicine-resistant hemodynamic changes have resulted in further
research on new treatment modalities in addition to classical treatments. In the
last decade, the sepsis physiopathology has been elucidated. Various therapeutic
agents have been used in addition to antibiotherapy, but no satisfactory results
have been obtained. This review summarizes the sepsis pathophysiology, current
treatment protocols, and new approaches.
PMID- 28416936
TI - Reentrance of Azygos Vein into Azygos Fissure After Pneumothorax.
AB - Empty azygos fissure implies dislocation of the azygos vein to the mediastinal
side of the right upper lobe from azygos fissure, which is usually secondary to
pneumothorax, pleural effusion, parenchymal fibrosis, vertebral collapse or
persistent vomiting. We are presenting here a case where a separated azygos vein
in CT and radiography images was noted. Moreover, in the follow-up images, it
appeared that the complete reexpansion of the right lung resulted in reentrance
of the azygos vein into azygos fissure in its native position.
PMID- 28416937
TI - Expansion of the Rib Head: A Novel Computed Tomographic Feature of Supernumerary
Intrathoracic Ribs.
AB - Intrathoracic ribs are very rare congenital anomalies. Approximately 50 cases
have been reported in the literature till date. They are usually present on the
right side, between the third and eighth ribs without sex predominance. They may
originate from a vertebral body or the proximal or distal part of a rib. In most
cases, they are asymptomatic, but they may be associated with developmental
abnormalities of ribs and vertebrae. The diagnosis is important to prevent
further investigation or intervention. Here we present two rare cases with
supernumerary intrathoracic rib and describe a novel sign, namely expansion of
the rib head. To the best of our knowledge, this is the shortest supernumerary
intrathoracic rib, reported in the literature, on the left side originating from
the head of the second rib, which could have been misdiagnosed as osteochondroma
due to its atypical features.
PMID- 28416939
TI - A Systemic-Onset Juvenile Idiopathic Arthritis Patient with Reduced Anakinra
Treatment Admitted with an Attack.
AB - Interleukin-1 plays an important role in the pathogenesis of systemic-onset
juvenile idiopathic arthritis (SoJIA), and the use of anti-interleukin-1 therapy
has been increasing. We report a case of a 14-year-old male patient with SoJIA.
He was in remission with anakinra treatment for almost 2 years. When we extended
the therapeutic range and decreased the dose (1 mg/kg twice a week), he developed
symptoms mimicking pulmonary embolism and cardiac ischemia. Increased cardiac
enzyme levels and echocardiographic findings were interpreted as myopericarditis.
Pulmonary computed tomography angiography revealed no thrombus. An SoJIA attack
was considered because of high level of acute-phase reactants and clinical
findings. Intensive immunosuppressive therapy with 2 mg/kg/day anakinra was
reinitiated. Clinical and laboratory parameters began to improve on the fifth day
of treatment. Thus, anti-interleukin-1 therapy is very important in patients with
SoJIA. Although the treatment dose was gradually reduced and the therapeutic
range was extended, it is noteworthy that the case progressed to a severe
clinical condition. Broad prospective studies regarding whether, how long, and
for what reasons the dosages of these drugs should be reduced in patients with
SoJIA with no genetic disorders are required.
PMID- 28416938
TI - Combined Systemic and Hysteroscopic Intra-Amniotic Injection of Methotrexate
Associated with Hysteroscopic Resection for Cervical Pregnancy: A Cutting-Edge
Approach for an Uncommon Condition.
AB - This case report of a 36-year-old woman with a diagnosis of cervical pregnancy
describes a novel approach to this rare form of ectopic pregnancy, which was
successfully treated with systemic and local methotrexate (MTX) therapy combined
with hysteroscopic resection. After local and systemic administration of MTX, the
patient underwent hysteroscopic resection of the cervical pregnancy using a 27
bipolar resectoscope with a 4-mm loop. The cervical pregnancy was completely
treated, and satisfactory hemostasis was achieved with electrocoagulation. The
reported case and literature review demonstrate that the combination of systemic
and local (hysteroscopic) administration of MTX with hysteroscopic resection
could offer the possibility of a safe, successful, minimally invasive, and
fertility-sparing surgical treatment for cervical pregnancy.
PMID- 28416940
TI - A Patient with Anterior, Apical, Transitional Zone Prostate Cancer Missed Twice
by Standard Biopsy.
PMID- 28416941
TI - A Family from Turkey with Bartsocas-Papas Syndrome.
PMID- 28416942
TI - The End of a Long Debate: Methylenetetrahydrofolate Reductase Gene Polymorphisms
do not Increase Thrombosis Risk.
PMID- 28416943
TI - Editor's Introduction to This Issue (G&I 15:1, 2017).
PMID- 28416944
TI - Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney
Transplantation.
AB - Early detection and proper management of kidney rejection are crucial for the
long-term health of a transplant recipient. Recipients are normally monitored by
serum creatinine measurement and sometimes with graft biopsies. Donor-derived
cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine
may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as
a system for monitoring graft status using single nucleotide polymorphism (SNP)
based detection of donor DNA in plasma or urine. We compared the detection
abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was
the most accurate and sensitive. Plasma and/or urine samples were isolated from
34 kidney recipients at multiple time points after transplantation, and analyzed
by dPCR using the QX200. We found that donor DNA was almost undetectable in
plasma DNA samples, whereas a high percentage of donor DNA was measured in urine
DNA samples, indicating that urine is a good source of cfDNA for patient
monitoring. We found that at least 24% of the highly polymorphic SNPs used to
identify individuals could also identify donor cfDNA in transplant patient
samples. Our results further showed that autosomal, sex-specific, and
mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we
found that donor-derived cfDNA measurement by dPCR was not sufficient to predict
a patient's clinical condition. Our results indicate that donor-derived cfDNA is
not an accurate predictor of kidney status in kidney transplant patients.
PMID- 28416945
TI - A ChIP-Seq Data Analysis Pipeline Based on Bioconductor Packages.
AB - Nowadays, huge volumes of chromatin immunoprecipitation-sequencing (ChIP-Seq)
data are generated to increase the knowledge on DNA-protein interactions in the
cell, and accordingly, many tools have been developed for ChIP-Seq analysis.
Here, we provide an example of a streamlined workflow for ChIP-Seq data analysis
composed of only four packages in Bioconductor: dada2, QuasR, mosaics, and
ChIPseeker. 'dada2' performs trimming of the high-throughput sequencing data.
'QuasR' and 'mosaics' perform quality control and mapping of the input reads to
the reference genome and peak calling, respectively. Finally, 'ChIPseeker'
performs annotation and visualization of the called peaks. This workflow runs
well independently of operating systems (e.g., Windows, Mac, or Linux) and
processes the input fastq files into various results in one run. R code is
available at github: https://github.com/ddhb/Workflow_of_Chipseq.git.
PMID- 28416946
TI - Use of Graph Database for the Integration of Heterogeneous Biological Data.
AB - Understanding complex relationships among heterogeneous biological data is one of
the fundamental goals in biology. In most cases, diverse biological data are
stored in relational databases, such as MySQL and Oracle, which store data in
multiple tables and then infer relationships by multiple-join statements.
Recently, a new type of database, called the graph-based database, was developed
to natively represent various kinds of complex relationships, and it is widely
used among computer science communities and IT industries. Here, we demonstrate
the feasibility of using a graph-based database for complex biological
relationships by comparing the performance between MySQL and Neo4j, one of the
most widely used graph databases. We collected various biological data (protein
protein interaction, drug-target, gene-disease, etc.) from several existing
sources, removed duplicate and redundant data, and finally constructed a graph
database containing 114,550 nodes and 82,674,321 relationships. When we tested
the query execution performance of MySQL versus Neo4j, we found that Neo4j
outperformed MySQL in all cases. While Neo4j exhibited a very fast response for
various queries, MySQL exhibited latent or unfinished responses for complex
queries with multiple-join statements. These results show that using graph-based
databases, such as Neo4j, is an efficient way to store complex biological
relationships. Moreover, querying a graph database in diverse ways has the
potential to reveal novel relationships among heterogeneous biological data.
PMID- 28416947
TI - DNA Methylation Profiles of Blood Cells Are Distinct between Early-Onset Obese
and Control Individuals.
AB - Obesity is a highly prevalent, chronic disorder that has been increasing in
incidence in young patients. Both epigenetic and genetic aberrations may play a
role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic
analyses will advance our understanding of the detailed molecular mechanisms
underlying obesity and aid in the selection of potential biomarkers for obesity
in youth. Here, we performed microarray-based DNA methylation and gene expression
profiling of peripheral white blood cells obtained from six young, obese
individuals and six healthy controls. We observed that the hierarchical
clustering of DNA methylation, but not gene expression, clearly segregates the
obese individuals from the controls, suggesting that the metabolic disturbance
that occurs as a result of obesity at a young age may affect the DNA methylation
of peripheral blood cells without accompanying transcriptional changes. To
examine the genome-wide differences in the DNA methylation profiles of young
obese and control individuals, we identified differentially methylated CpG sites
and investigated their genomic and epigenomic contexts. The aberrant DNA
methylation patterns in obese individuals can be summarized as relative gains and
losses of DNA methylation in gene promoters and gene bodies, respectively. We
also observed that the CpG islands of obese individuals are more susceptible to
DNA methylation compared to controls. Our pilot study suggests that the genome
wide aberrant DNA methylation patterns of obese individuals may advance not only
our understanding of the epigenomic pathogenesis but also early screening of
obesity in youth.
PMID- 28416948
TI - Comparative Analysis of Predicted Gene Expression among Crenarchaeal Genomes.
AB - Research into new methods for identifying highly expressed genes in anonymous
genome sequences has been going on for more than 15 years. We presented here an
alternative approach based on modified score of relative codon usage bias to
identify highly expressed genes in crenarchaeal genomes. The proposed algorithm
relies exclusively on sequence features for identifying the highly expressed
genes. In this study, a comparative analysis of predicted highly expressed genes
in five crenarchaeal genomes was performed using the score of Modified Relative
Codon Bias Strength (MRCBS) as a numerical estimator of gene expression level. We
found a systematic strong correlation between Codon Adaptation Index and MRCBS.
Additionally, MRCBS correlated well with other expression measures. Our study
indicates that MRCBS can consistently capture the highly expressed genes.
PMID- 28416949
TI - Circulating Tumor DNA in a Breast Cancer Patient's Plasma Represents Driver
Alterations in the Tumor Tissue.
AB - Tumor tissues from biopsies or surgery are major sources for the next generation
sequencing (NGS) study, but these procedures are invasive and have limitation to
overcome intratumor heterogeneity. Recent studies have shown that driver
alterations in tumor tissues can be detected by liquid biopsy which is a less
invasive technique capable of both capturing the tumor heterogeneity and
overcoming the difficulty in tissue sampling. However, it is still unclear
whether the driver alterations in liquid biopsy can be detected by targeted NGS
and how those related to the tissue biopsy. In this study, we performed whole
exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7
frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS,
the same variant initially identified in the tumor tissue was also detected with
low variant allele frequency. This mutation was subsequently validated by digital
polymerase chain reaction in liquid biopsy. Our result confirm that driver
alterations identified in the tumor tissue were detected in liquid biopsy by
targeted NGS as well, and suggest that a higher depth of sequencing coverage is
needed for detection of genomic alterations in a liquid biopsy.
PMID- 28416950
TI - TRAPR: R Package for Statistical Analysis and Visualization of RNA-Seq Data.
AB - High-throughput transcriptome sequencing, also known as RNA sequencing (RNA-Seq),
is a standard technology for measuring gene expression with unprecedented
accuracy. Numerous bioconductor packages have been developed for the statistical
analysis of RNA-Seq data. However, these tools focus on specific aspects of the
data analysis pipeline, and are difficult to appropriately integrate with one
another due to their disparate data structures and processing methods. They also
lack visualization methods to confirm the integrity of the data and the process.
In this paper, we propose an R-based RNA-Seq analysis pipeline called TRAPR, an
integrated tool that facilitates the statistical analysis and visualization of
RNA-Seq expression data. TRAPR provides various functions for data management,
the filtering of low-quality data, normalization, transformation, statistical
analysis, data visualization, and result visualization that allow researchers to
build customized analysis pipelines.
PMID- 28416951
TI - Spirometry and Bronchodilator Test.
AB - Spirometry is a physiological test for assessing the functional aspect of the
lungs using an objective indicator to measure the maximum amount of air that a
patient can inhale and exhale. Acceptable spirometry testing needs to be
conducted three times by an acceptable and reproducible method for determining
forced vital capacity (FVC). Until the results of three tests meet the criteria
of reproducibility, the test should be repeated up to eight times. Interpretation
of spirometry should be clear, concise, and informative. Additionally, spirometry
should guarantee optimal quality prior to the interpreting spirometry results.
Our guideline adopts a fixed normal predictive value instead of the lower limit
of normal as the reference value because fixed value is more convenient and also
accepts FVC instead of vital capacity (VC) because measurement of VC using a
spirometer is impossible. The bronchodilator test is a method for measuring the
changes in lung capacity after inhaling a short-acting beta-agonist that dilates
the airway. When an obstructive ventilatory defect is observed, this test helps
to diagnose and evaluate asthma and chronic obstructive pulmonary disease by
measuring reversibility with the use of an inhaled bronchodilator. A positive
response to a bronchodilator is generally defined as an increase of >=12% and
>=200 mL as an absolute value compared with a baseline in either forced
expiratory volume at 1 second or FVC.
PMID- 28416953
TI - Response Evaluation of Chemotherapy for Lung Cancer.
AB - Assessing response to therapy allows for prospective end point evaluation in
clinical trials and serves as a guide to clinicians for making decisions. Recent
prospective and randomized trials suggest the development of imaging techniques
and introduction of new anti-cancer drugs. However, the revision of methods, or
proposal of new methods to evaluate chemotherapeutic response, is not enough.
This paper discusses the characteristics of the Response Evaluation Criteria In
Solid Tumor (RECIST) version 1.1 suggested in 2009 and used widely by experts. It
also contains information about possible dilemmas arising from the application of
response assessment by the latest version of the response evaluation method, or
recently introduced chemotherapeutic agents. Further data reveals the problems
and limitations caused by applying the existing RECIST criteria to anti-cancer
immune therapy, and the application of a new technique, immune related response
criteria, for the response assessment of immune therapy. Lastly, the paper
includes a newly developing response evaluation method and suggests its
developmental direction.
PMID- 28416952
TI - Asthma and the Risk of Rheumatoid Arthritis: An Insight into the Heterogeneity
and Phenotypes of Asthma.
AB - Asthma is traditionally regarded as a chronic airway disease, and recent
literature proves its heterogeneity, based on distinctive clusters or phenotypes
of asthma. In defining such asthma clusters, the nature of comorbidity among
patients with asthma is poorly understood, by assuming no causal relationship
between asthma and other comorbid conditions, including both communicable and
noncommunicable diseases. However, emerging evidence suggests that the status of
asthma significantly affects the increased susceptibility of the patient to both
communicable and noncommunicable diseases. Specifically, the impact of asthma on
susceptibility to noncommunicable diseases such as chronic systemic inflammatory
diseases (e.g., rheumatoid arthritis), may provide an important insight into
asthma as a disease with systemic inflammatory features, a conceptual
understanding between asthma and asthma-related comorbidity, and the potential
implications on the therapeutic and preventive interventions for patients with
asthma. This review discusses the currently under-recognized clinical and
immunological phenotypes of asthma; specifically, a higher risk of developing a
systemic inflammatory disease such as rheumatoid arthritis and their
implications, on the conceptual understanding and management of asthma. Our
discussion is divided into three parts: literature summary on the relationship
between asthma and the risk of rheumatoid arthritis; potential mechanisms
underlying the association; and implications on asthma management and research.
PMID- 28416955
TI - Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with
Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease.
AB - BACKGROUND: Recently, increased levels of high-mobility group box 1 protein
(HMGB1) have been identified in various inflammatory conditions and infections.
However, no studies have evaluated the HMGB1 level in nontuberculous
mycobacterial (NTM) lung disease, and compared it to mycobacterial lung disease.
METHODS: A total of 60 patients newly diagnosed with NTM lung disease, 44 culture
positive pulmonary tuberculosis (TB) patients, and 34 healthy controls, were
included in this study. The serum HMGB1 concentrations were quantified using
HMGB1 enzyme-linked immunosorbent assay kits. RESULTS: Serum HMGB1 level in
patients with pulmonary TB or NTM lung disease, was significantly lower than that
of the healthy controls. In addition, the serum HMGB1 level in TB patients was
significantly lower than patients with NTM lung disease. However, the levels in
NTM patient subgroups did not differ according to the causative species, disease
progression, and disease phenotype. CONCLUSION: Although low levels of serum
HMGB1 has the potential to be a marker of mycobacterial lung disease, these
levels were unable to differentiate disease progression and disease phenotype in
NTM lung diseases.
PMID- 28416954
TI - Current Status of Fluoroquinolone Use for Treatment of Tuberculosis in a Tertiary
Care Hospital in Korea.
AB - BACKGROUND: Fluoroquinolones are considered important substitutes for the
treatment of tuberculosis. This study investigates the current status of
fluoroquinolone for the treatment of tuberculosis. METHODS: In 2009, a
retrospective analysis was performed at one tertiary referral center for 953
patients diagnosed with tuberculosis. RESULTS: A total of 226 patients (23.6%),
who received fluoroquinolone at any time during treatment for tuberculosis, were
enrolled in this study. The most common reasons for fluoroquinolone use were
adverse events due to other anti-tuberculosis drugs (52.7%), drug resistance
(23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the
most commonly administered fluoroquinolone, followed by levofloxacin (36.3%,
82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from
fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas
fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The
most common fluoroquinolone-related adverse events were gastrointestinal problems
(3.5%, 8/226). There were no significant differences in the treatment success
rate between the fluoroquinolone and fluoroquinolone-naive groups (78.3% vs.
78.4%, respectively). CONCLUSION: At our institution, fluoroquinolones are
commonly used for the treatment of both multidrug-resistant tuberculosis and
susceptible tuberculosis, especially as a substitute for adverse event-related
drugs. Considering the low adverse event rates and the comparable treatment
success rates, fluoroquinolones seem to be an invaluable drug for the treatment
of tuberculosis.
PMID- 28416956
TI - Mutations in Streptomycin Resistance Genes and Their Relationship to Streptomycin
Resistance and Lineage of Mycobacterium tuberculosis Thai Isolates.
AB - BACKGROUND: Streptomycin (SM) is recommended by the World Health Organization
(WHO) as a part of standard regimens for retreating multidrug-resistant
tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19%
in Thailand. To date, information on SM resistance (SMR) gene mutations
correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In
this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and
their association to SMR and the lineage of M. tuberculosis were explored.
METHODS: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were
identified by spoligotyping. Drug susceptibility profiles were evaluated by the
absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55
SM-susceptible isolates were examined by DNA sequencing. RESULTS: Three rpsL
(Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations
were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was
the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates
(p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and
gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis
Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking
rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C,
615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored.
This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1.
CONCLUSION: Our study suggested that the majority of SMR in M. tuberculosis Thai
isolates were responsible by rpsL and gidB polymorphisms constantly providing the
novel lineage specific makers.
PMID- 28416957
TI - The Need for a Well-Organized, Video-Assisted Asthma Education Program at Korean
Primary Care Clinics.
AB - BACKGROUND: The purpose of this study was to assess the effect of our new video
assisted asthma education program on patients' knowledge regarding asthma and
asthma control. METHODS: Adult asthmatics who were diagnosed by primary care
physicians and followed for at least 1 year were educated via smart devices and
pamphlets. The education sessions were carried out three times at 2-week
intervals. Each education period lasted at most 5 minutes. The effectiveness was
then evaluated using questionnaires and an asthma control test (ACT). RESULTS:
The study enrolled 144 patients (mean age, 56.7+/-16.7 years). Half of the
patients had not been taught how to use their inhalers. After participating in
the education program, the participants' understanding of asthma improved
significantly across all six items of a questionnaire assessing their general
knowledge of asthma. The proportion of patients who made errors while
manipulating their inhalers was reduced to less than 10%. The ACT score increased
from 16.6+/-4.6 to 20.0+/-3.9 (p<0.001). The number of asthmatics whose ACT score
was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude
of improvement in the ACT score did not differ between patients who received an
education session at least three times within 1 year and those who had not. The
majority of patients agreed to the need for an education program (95.8%) and
showed a willingness to pay an additional cost for the education (81.9%).
CONCLUSION: This study indicated that our newly developed education program would
become an effective component of asthma management in primary care clinics.
PMID- 28416958
TI - Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical
Outcome.
AB - BACKGROUND: Although the World Health Organization (WHO) classification of lung
squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for
lung SCC subsets remain unclear. We investigated whether the morphologic
characteristics of lung SCC, including keratinization, were associated with
clinical parameters and clinical outcome of patients. METHODS: A total of 81
patients who underwent curative surgical resection of diagnosed lung SCC, were
enrolled in this study. Attributes such as keratinization, tumor budding, single
cell invasion, and nuclear size within the tumor, as well as immunohistochemistry
of Bcl-xL and pS6 expressions, were evaluated. RESULTS: The keratinizing and
nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and
morphologic parameters such as nuclear diameter, tumor budding, and single cell
invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%)
had a history of smoking, whereas the nonkeratinizing group had a relatively
higher proportion of never-smokers relative to the keratinizing group (24.0% vs.
2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of
mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates
keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may
inhibit keratinization), did not correlate significantly with the presence of
keratinization. Patients with the keratinizing subtype had a significantly
shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test),
and a multivariate analysis showed that keratinization was an independent, poor
prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090-5.233;
p=0.030). CONCLUSION: In lung SCC, keratinization is associated with a poor
prognosis, and might be associated with smoking.
PMID- 28416959
TI - Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant
Non-Small Cell Lung Cancer.
AB - BACKGROUND: Third-generation tyrosine kinase inhibitors of the epidermal growth
factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell
lung cancer (NSCLC) patients with acquired resistance resulting from the T790M
mutation. However, since almost 50% patients with the acquired resistance do not
harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs
may be a more viable therapeutic option. Here, we identified positive response
predictors to retreatment, in patients who switched to a different EGFR-TKI,
following initial treatment failure. METHODS: This study retrospectively reviewed
the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had
progressed following initial treatment with gefitinib or erlotinib, and who had
switched to a different first-generation EGFR-TKI during subsequent retreatment.
To identify high response rate predictors in the changed EGFR-TKI retreatment, we
analyzed the relationship between clinical and demographic parameters, and
positive clinical outcomes, following retreatment with EGFR-TKI. RESULTS:
Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received
erlotinib as their first EGFR-TKI treatment. Following retreatment with a
different EGFR-TKI, the overall response and disease control rates were 21.4% and
64.3%, respectively. There was no significant association between their overall
responses. The median progression-free survival (PFS) after retreatment was 2.0
months. However, PFS was significantly longer in patients whose time to
progression was >=10 months following initial EGFR-TKI treatment, who had a
mutation of exon 19, or whose treatment interval was <90 days. CONCLUSION: In
patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI
retreatment may be a salvage therapy for individuals possessing positive
retreatment response predictors.
PMID- 28416960
TI - Medical Thoracoscopy in Pleural Disease: Experience from a One-Center Study.
AB - BACKGROUND: Medical thoracoscopy (MT) is a minimally invasive, endoscopic
procedure for exploration of the pleural cavity under conscious sedation and
local anesthesia. MT has been performed at the Seoul National University Hospital
since February 2014. This paper summarizes the findings and outcomes of MT cases
at this hospital. METHODS: Patients who had undergone MT were enrolled in the
study. MT was performed by pulmonologists, using both rigid and semi-rigid
thoracoscopes. During the procedure, patients were under conscious sedation with
fentanyl and midazolam. Medical records were reviewed for clinical data. RESULTS:
From February 2014 to January 2016, 50 procedures (47 cases) were performed
(diagnostic MT, 26 cases; therapeutic MT, 24 cases). The median age of patients
was 66 years (59-73 years), and 38 patients (80.9%) were male. The median
procedure duration from initial incision to insertion of the chest tube was 37
minutes. The median doses of fentanyl and midazolam were 50 ug and 5 mg,
respectively. All procedures were performed without unexpected events. Of the 26
cases of pleural disease with an unknown cause, 19 were successfully diagnosed
using MT. Additionally, diagnostic MT provided clinically useful information in
the other six patients. Therapeutic MT was very effective for treatment of
malignant pleural effusion or empyema. The median number of days with chest tube
drainage was 6 (3 days for diagnostic MT and 8 days for therapeutic MT).
CONCLUSION: MT is a useful and necessary procedure for both diagnosis and
treatment of pleural diseases.
PMID- 28416961
TI - Predictive Factors of Methicillin-Resistant Staphylococcus aureus Infection in
Elderly Patients with Community-Onset Pneumonia.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a
severe and life-threatening disease in patients with community-onset (CO)
pneumonia. However, the current guidelines lack specificity for a screening test
for MRSA infection. METHODS: This study was retrospectively conducted in elderly
patients aged >=65 years, who had contracted CO-pneumonia during hospitalization
at the Jeju National University Hospital, between January 2012 and December 2014.
We analyzed the risk factors of MRSA in these patients and developed a scoring
system to predict MRSA infection. RESULTS: A total of 762 patients were enrolled
in this study, including 19 (2.4%) with MRSA infection. Healthcare-associated
pneumonia (HCAP) showed more frequent MRSA infection compared to community
acquired pneumonia (4.4% vs. 1.5%, respectively; p=0.016). In a multivariate
logistic regression analysis, admissions during the influenza season (odds ratio
[OR], 2.896; 95% confidence interval [CI], 1.022-8.202; p=0.045), chronic kidney
disease (OR, 3.555; 95% CI, 1.157-10.926; p=0.027), and intensive care unit
admission (OR, 3.385; 95% CI, 1.035-11.075; p=0.044) were identified as
predictive factors for MRSA infection. However, the presence of HCAP was not
significantly associated with MRSA infection (OR, 1.991; 95% CI, 0.720-5.505;
p=0.185). The scoring system consisted of three variables based on the
multivariate analysis, and showed moderately accurate diagnostic prediction (area
under curve, 0.790; 95% CI, 0.680-0.899; p<0.001). CONCLUSION: MRSA infection
would be considered in elderly CO-pneumonia patients, with three risk factors
identified herein. When managing elderly patients with pneumonia, clinicians
might keep in mind that these risk factors are associated with MRSA infection,
which may help in selecting appropriate antibiotics.
PMID- 28416962
TI - Cutaneous Leukocytoclastic Vasculitis with Gastrointestinal Involvement after
Anti-Tuberculosis Treatment.
PMID- 28416963
TI - Mitochondrial acclimation potential to ocean acidification and warming of Polar
cod (Boreogadus saida) and Atlantic cod (Gadus morhua).
AB - BACKGROUND: Ocean acidification and warming are happening fast in the Arctic but
little is known about the effects of ocean acidification and warming on the
physiological performance and survival of Arctic fish. RESULTS: In this study we
investigated the metabolic background of performance through analyses of cardiac
mitochondrial function in response to control and elevated water temperatures and
PCO2 of two gadoid fish species, Polar cod (Boreogadus saida), an endemic Arctic
species, and Atlantic cod (Gadus morhua), which is a temperate to cold eurytherm
and currently expanding into Arctic waters in the wake of ocean warming. We
studied their responses to the above-mentioned drivers and their acclimation
potential through analysing the cardiac mitochondrial function in permeabilised
cardiac muscle fibres after 4 months of incubation at different temperatures
(Polar cod: 0, 3, 6, 8 degrees C and Atlantic cod: 3, 8, 12, 16 degrees C),
combined with exposure to present (400MUatm) and year 2100 (1170MUatm) levels of
CO2. OXPHOS, proton leak and ATP production efficiency in Polar cod were similar
in the groups acclimated at 400MUatm and 1170MUatm of CO2, while incubation at 8
degrees C evoked increased proton leak resulting in decreased ATP production
efficiency and decreased Complex IV capacity. In contrast, OXPHOS of Atlantic cod
increased with temperature without compromising the ATP production efficiency,
whereas the combination of high temperature and high PCO2 depressed OXPHOS and
ATP production efficiency. CONCLUSIONS: Polar cod mitochondrial efficiency
decreased at 8 degrees C while Atlantic cod mitochondria were more resilient to
elevated temperature; however, this resilience was constrained by high PCO2. In
line with its lower habitat temperature and higher degree of stenothermy, Polar
cod has a lower acclimation potential to warming than Atlantic cod.
PMID- 28416964
TI - A nondestructive method to estimate the chlorophyll content of Arabidopsis
seedlings.
AB - BACKGROUND: Chlorophyll content decreases in plants under stress conditions,
therefore it is used commonly as an indicator of plant health. Arabidopsis
thaliana offers a convenient and fast way to test physiological phenotypes of
mutations and treatments. However, chlorophyll measurements with conventional
solvent extraction are not applicable to Arabidopsis leaves due to their small
size, especially when grown on culture dishes. RESULTS: We provide a
nondestructive method for chlorophyll measurement whereby the red, green and blue
(RGB) values of a color leaf image is used to estimate the chlorophyll content
from Arabidopsis leaves. The method accommodates different profiles of digital
cameras by incorporating the ColorChecker chart to make the digital negative
profiles, to adjust the white balance, and to calibrate the exposure rate
differences caused by the environment so that this method is applicable in any
environment. We chose an exponential function model to estimate chlorophyll
content from the RGB values, and fitted the model parameters with physical
measurements of chlorophyll contents. As proof of utility, this method was used
to estimate chlorophyll content of G protein mutants grown on different sugar to
nitrogen ratios. CONCLUSION: This method is a simple, fast, inexpensive, and
nondestructive estimation of chlorophyll content of Arabidopsis seedlings. This
method lead to the discovery that G proteins are important in sensing the C/N
balance to control chlorophyll content in Arabidopsis.
PMID- 28416965
TI - A crisis of protection and safe passage: violence experienced by
migrants/refugees travelling along the Western Balkan corridor to Northern
Europe.
AB - BACKGROUND: Pushed by ongoing conflicts and pulled by the desire for a better
life, over one million migrants/refugees transited Balkan countries and arrived
in Europe during 2015 and early 2016. To curb this influx, European countries
instituted restrictive migration policies often characterized by building of
razor-wire border fences and border closures. Among migrants/refugees who
received mental health care in Serbia while travelling through Balkan countries
to Northern Europe, we assessed the prevalence and patterns of violent events
experienced including physical trauma. METHODS: A mixed methods study among
migrants/refugees attending mobile mental health clinics run by Medecins sans
Frontieres (MSF) between July 2015 and June 2016, in Serbia - a main transit hub
to European countries. Clinics were conducted according to MSF guidelines by
experienced psychologists who were supported by cultural mediators. The main
outcome measures were violent events and associated physical trauma. RESULTS: Of
992 migrants/refugees attending MSF mental health clinics, the majority (72%)
were from Syria and Afghanistan and included vulnerable groups (14%) such as
unaccompanied minors and pregnant women. The most frequent mental health
symptoms/signs were anxiety (29%) and adjustment reactions (26%). Of the 992
migrants/refugees, 270 (27%) had experienced violent events during their journey.
Signs of physical trauma due to acts of violence were seen in 223(22%) of the 992
individuals, 144 (65%) being perpetrated by State authorities and involving women
(11%) and children (13%). Border closures along the Balkan route were associated
with a dramatic decrease in registered migrants/refugee arrivals in Serbia.
Conversely, among those that made it across the borders, an increasing linear
trend in reported violent events was observed at MSF mental health clinics (X2
for linear trend, P <0 . 001). Qualitative evidence corroborated with
quantitative findings. CONCLUSIONS: Nearly one-in-three migrants/refugees seen in
MSF clinics experienced violent events including physical trauma along their
journey. State authorities, including those in European countries were the
perpetrators in over half of such events which were associated with border
closures. There is "a crisis of protection and safe passage" which needs to
change towards one of respect for the principles of international human rights
and refugee law.
PMID- 28416966
TI - An overview of mental health care system in Kilifi, Kenya: results from an
initial assessment using the World Health Organization's Assessment Instrument
for Mental Health Systems.
AB - BACKGROUND: Little is known about the state of mental health systems in Kenya. In
2010, Kenya promulgated a new constitution, which devolved national government
and the national health system to 47 counties including Kilifi County. There is
need to provide evidence from mental health systems research to identify priority
areas in Kilifi's mental health system for informing county health sector
decision making. We conducted an initial assessment of state of mental health
systems in Kilifi County and documented resources, policy and legislation and
spectrum of mental, neurological and substance use disorders. METHODS: This was a
pilot study that used the brief version of the World Health Organization's
Assessment Instrument for Mental Health Systems Version 2.2 to collect data. Data
collection was based on the year 2014. RESULTS: Kilifi county has two public
psychiatric outpatient units that are part of general hospitals. There is no
standalone mental hospital in Kilifi. There are no inpatients or community based
facilities for people with mental health problems. Although the psychiatric
facilities in Kilifi have an essential drugs list, supply of drugs is erratic
with frequent shortages. There is no psychiatrist or psychologist in Kilifi with
only two psychiatric nurses for a population of approximately 1.2 million people.
Schizophrenia was the commonest reason for visiting outpatient facilities (47.1%)
while suicidal ideation was the least common (0.4%). Kenya's mental health
policy, which is being used by Kilifi County, is outdated and does not cater for
the current mental health needs of Kilifi. There is no specific legislation to
protect the rights of people with mental health problems. No budget exists
specifically for mental health care. There have been no efforts to integrate
mental health care into primary care in Kilifi, and there is no empirical
research work to evaluate its feasibility. CONCLUSION: There is an urgent need to
increase resources allocated for mental health in particular infrastructure and
human resource. Policy and legislations need to be established to protect the
rights of people with mental illnesses, and mental health should be integrated
with primary care to increase access to services.
PMID- 28416967
TI - Rescuing ethanol photosynthetic production of cyanobacteria in non-sterilized
outdoor cultivations with a bicarbonate-based pH-rising strategy.
AB - BACKGROUND: Ethanol photosynthetic production based on cyanobacteria cell
factories utilizing CO2 and solar energy provides an attractive solution for
sustainable production of green fuels. However, the scaling up processes of
cyanobacteria cell factories were usually threatened or even devastated by
biocontaminations, which restricted biomass or products accumulations of
cyanobacteria cells. Thus it is of great significance to develop reliable
biocontamination-controlling strategies for promoting ethanol photosynthetic
production in large scales. RESULTS: The scaling up process of a previously
developed Synechocystis strain Syn-HZ24 for ethanol synthesis was severely
inhibited and devastated by a specific contaminant, Pannonibacter phragmitetus,
which overcame the growths of cyanobacteria cells and completely consumed the
ethanol accumulation in the cultivation systems. Physiological analysis revealed
that growths and ethanol-consuming activities of the contaminant were sensitive
to alkaline conditions, while ethanol-synthesizing cyanobacteria strain Syn-HZ24
could tolerate alkaline pH conditions as high as 11.0, indicating that pH
increasing strategy might be a feasible approach for rescuing ethanol
photosynthetic production in outdoor cultivation systems. Thus, we designed and
evaluated a Bicarbonate-based Integrated Carbon Capture System (BICCS) derived pH
rising strategy to rescue the ethanol photosynthetic production in non-sterilized
conditions. In lab scale artificially simulated systems, pH values of BG11
culture medium were maintained around 11.0 by 180 mM NaHCO3 and air steam, under
which the infection of Pannonibacter phragmitetus was significantly restricted,
recovering ethanol production of Syn-HZ24 by about 80%. As for outdoor
cultivations, ethanol photosynthetic production of Syn-HZ24 was also successfully
rescued by the BICCS-derived pH-rising strategy, obtaining a final ethanol
concentration of 0.9 g/L after 10 days cultivation. CONCLUSIONS: In this work, a
novel product-consuming biocontamination pattern in cyanobacteria cultivations,
causing devastated ethanol photosynthetic production, was identified and
characterized. Physiological analysis of the essential ethanol-consuming
contaminant directed the design and application of a pH-rising strategy, which
effectively and selectively controlled the contamination and rescued ethanol
photosynthetic production. Our work demonstrated the importance of reliable
contamination control systems and strategies for large scale outdoor cultivations
of cyanobacteria, and provided an inspiring paradigm for targeting effective
solutions.
PMID- 28416968
TI - Safety and efficacy of resistive polymer versus forced air warming in total joint
surgery.
AB - BACKGROUND: Forced-air warming is used as a mechanism to prevent hypothermia and
adverse outcomes associated with hypothermia among patients undergoing surgery.
Patient safety in healthcare includes the use of devices and technology that
minimize potential adverse events to patients. The present study sought to
compare the capabilities of patient warming between two different devices that
use different mechanisms of warming: forced-air warming and non-air warming.
METHODS: One hundred twenty patients undergoing total hip or total knee
arthroplasty received patient warming via a forced warming device or non-air
warming fabric conductive material. The project was part of a quality improvement
initiative to identify warming devices effective in maintaining normothermic
patient core temperatures during orthopedic surgery. RESULTS: Forced-air warming
and non-air warming achieved similar results in maintaining the core temperature
of patients undergoing total knee or hip arthroplasty. No adverse events were
reported in either group. Operating room staff observed that the non-air warming
device was less noisy and appreciated the disposable covers that could be changed
after each surgical case. CONCLUSIONS: These findings demonstrate that
hypothermia is achieved by both forced-air and non-forced air warming devices
among total knee and hip arthroplasty patients. The potential for airflow
disruption is present with the forced-air warming device and does not exist with
the non-forced air device. The disruption of laminar airflow may be associated
with surgical site infections. The disposable covers used to protect the device
and patient have potential implications for surgical site infection. Quality
improvement efforts aimed to enhance patient safety should include the
implementation of healthcare equipment with the least known or suspected risk.
PMID- 28416969
TI - Repeatability and agreement of ultrasonography with computed tomography for
evaluating forefoot structure in the coronal plane.
AB - BACKGROUND: Forefoot structure is important to understand some foot problems such
as hallux valgus and metatarsalgia. Ultrasonography (US) is a highly portable,
noninvasive, low cost, and fast imaging method, especially when compared to
magnetic resonance imaging (MRI), computed tomography (CT), and radiography. As
the use of US for evaluating forefoot bony structure has not been validated,
except for the presence of synovitis, erosions and bursitis within the forefoot
in people with inflammatory arthritis, the purpose of this study was to determine
whether US is a reliable method for evaluating forefoot structure. METHODS: Sixty
feet (30 women, age = 40.1 +/- 11.8 years) were examined by US and CT to assess
agreement with CT and repeatability of US evaluation of the 2nd metatarsal head
height, length between the medial sesamoid bone and 5th metatarsal head,
transverse arch height, transverse arch index, sesamoid rotation angle, and area
under the transverse arch. The measurement data were evaluated for agreement with
CT using the intra-class correlation coefficient (ICC)3, 1, Pearson correlation
coefficient, and Bland-Altman plot, and with ICC1, 1 for repeatability. RESULTS:
The ICC3, 1 values of 0.78-0.89, Pearson correlation coefficient of 0.78-0.90,
and Bland-Altman plots showed almost perfect agreements between the US and CT
method for all parameters, except the area under the transverse arch (AUTA). The
ICC1, 1 also showed perfect agreements (0.84-0.92) between two sets of US
measurements in all parameters. CONCLUSIONS: The US evaluation of forefoot
structure in the coronal plane showed good agreement with CT and repeatability of
two ultrasonograms in adult women. This reliable evaluation method of forefoot
structure can contribute to a quick clinical assessment screening for risk
factors of foot problems such as hallux valgus and metatarsalgia. However,
because of some limitations such as a lack of inter-observer reliability, more
research is needed to validate US evaluation of forefoot structure. TRIAL
REGISTRATION: The current study (trial registration number: R0297) was approved
by the Ethical Committee for Human Experiments of Kyoto University
(http://www.ec.med.kyoto-u.ac.jp) on December 3, 2015. The first participant in
this study was enrolled on November 17, 2015 and retrospectively registered.
PMID- 28416970
TI - DNA methylation profiling in peripheral lung tissues of smokers and patients with
COPD.
AB - BACKGROUND: Epigenetics changes have been shown to be affected by cigarette
smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect
several cellular and pathophysiological processes, acute exacerbations, and
comorbidity in the lungs of patients with chronic obstructive pulmonary disease
(COPD). We sought to determine whether genome-wide lung DNA methylation profiles
of smokers and patients with COPD were significantly different from non-smokers.
We isolated DNA from parenchymal lung tissues of patients including eight
lifelong non-smokers, eight current smokers, and eight patients with COPD and
analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip.
RESULTS: Our data revealed that the differentially methylated genes were related
to top canonical pathways (e.g., G beta gamma signaling, mechanisms of cancer,
and nNOS signaling in neurons), disease and disorders (organismal injury and
abnormalities, cancer, and respiratory disease), and molecular and cellular
functions (cell death and survival, cellular assembly and organization, cellular
function and maintenance) in patients with COPD. The genome-wide DNA methylation
analysis identified suggestive genes, such as NOS1AP, TNFAIP2, BID, GABRB1,
ATXN7, and THOC7 with DNA methylation changes in COPD lung tissues that were
further validated by pyrosequencing. Pyrosequencing validation confirmed hyper
methylation in smokers and patients with COPD as compared to non-smokers.
However, we did not detect significant differences in DNA methylation for
TNFAIP2, ATXN7, and THOC7 genes in smokers and COPD groups despite the changes
observed in the genome-wide analysis. CONCLUSIONS: Our study suggests that DNA
methylation in suggestive genes, such as NOS1AP, BID, and GABRB1 may be used as
epigenetic signatures in smokers and patients with COPD if the same is validated
in a larger cohort. Future studies are required to correlate DNA methylation
status with transcriptomics of selective genes identified in this study and
elucidate their role and involvement in the progression of COPD and its
exacerbations.
PMID- 28416971
TI - A multicenter study of the need of additional freezing for cryoballoon ablation
in patients with atrial fibrillation: The AD-Balloon study.
AB - BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone of catheter ablation
in patients with paroxysmal atrial fibrillation (PAF), and balloon-based ablation
has been recently performed worldwide. Ablation using the second-generation
cryoballoon (CB2) (Arctic Front AdvanceTM, Medtronic, MN, USA) is useful for PVI;
however, there is some debate concerning the optimal freezing time and number of
cycles after PVI is achieved. METHODS: The AD-Balloon study was designed as a
prospective, multicenter, randomized clinical trial to evaluate the optimal
strategy (freezing cycles) of CB2 ablation (UMIN Clinical Trials Registry
UMIN000020130). The main objective of this study is to investigate the need for
an additional freezing cycle after PVI in patients treated with CB2 ablation.
Patients will be randomly assigned in a 1:1 ratio to treatment with additional
freezing (AD group) or without additional freezing (non-AD group). In the AD
group, 3 min of additional freezing time will be applied in all pulmonary veins
after PVI is confirmed at the previous freezing cycle. In the non-AD group, no
additional freezing will be applied in all pulmonary veins after PVI is
confirmed. The primary endpoint of this study is the occurrence of atrial
tachyarrhythmias within a 1-year follow-up period. We will enroll 110 consecutive
patients with PAF. We will also investigate the usefulness of delayed-enhancement
magnetic resonance imaging to assess the ablation lesions caused by CB2 ablation.
RESULTS: The results of this study are currently under investigation. CONCLUSION:
The AD-Balloon study would assess the need for an additional freezing cycle after
PVI is achieved. Our findings may contribute to further improvement of the CB2
ablation procedure.
PMID- 28416972
TI - Crucial role of pulmonary vein firing as an initiator of typical atrial flutter:
Evidence of a close relationship between atrial fibrillation and typical atrial
flutter.
AB - BACKGROUND: Several studies reported that cavotricuspid isthmus-dependent atrial
flutter (typical AFL) frequently coexists with atrial fibrillation (AF); however,
the underlying mechanisms have not been fully investigated. This study aimed to
reveal the mechanisms of the initiation of typical AFL and the association
between typical AFL and AF. METHODS: Among 154 consecutive patients undergoing a
first catheter ablation of AF, we investigated the appearance and mechanism of
spontaneous initiation of typical AFL during catheter ablation. Then, we
retrospectively investigated 67 consecutive patients without a previous AF
episode who underwent typical AFL ablation. The occurrence and predictors of AF
after catheter ablation were evaluated. RESULTS: During AF ablation, spontaneous
initiation of typical AFL occurred during sinus rhythm in eight (5.2%) patients.
The initiations of typical AFL were pulmonary vein (PV) firings except in one
patient, in whom paroxysmal AF following superior vena cava firing initiated
reverse typical AFL after PV isolation. After typical AFL ablation, AF occurred
in 23 (34.3%) patients (mean follow up, 28.2+/-20.3 months). Kaplan-Meier
analysis showed the occurrence of AF after typical AFL ablation to be
significantly higher in the patients with a larger left atrial diameter over 40
mm (log-rank test, P=0.046). CONCLUSIONS: PV firing through AF played an
important role in initiating typical AFL. The occurrence of AF after typical AFL
ablation was high, and a dilated left atrium was associated with increased
occurrence of AF. These findings disclosed the close relationship between typical
AFL and AF, especially PV firing.
PMID- 28416973
TI - The utility of atrial pacing for identifying the electrical breakthrough sites
between the left atrium and pulmonary veins.
AB - BACKGROUND: Circumferential pulmonary vein (PV) isolation for atrial fibrillation
(AF) is occasionally difficult to achieve because electrical breakthrough sites
(EBSs) between the left atrium (LA) and PVs cannot be identified during ablation
especially in the carina regions. METHODS: The left PVs (Lt.PVs) of 60 AF
patients and the right PVs (Rt.PVs) of 37 patients undergoing PV isolation were
studied. When PV isolation was not achieved after the initial circumferential PV
isolation, atrial pacing was repeatedly performed from the distal coronary sinus
(CSd) and high right atrium (HRA), and the time interval from the stimulus to the
earliest PV potential (stimulus-PV interval) was measured using circular mapping
catheters at each PV until PV isolation was achieved. When PV isolation was
achieved via local Radiofrequency (RF) deliveries, those regions were diagnosed
as final EBSs. We classified the final EBSs into six segments for each PV
(anterior and posterior PV walls of the roof, carina, and bottom) and
investigated the relationship between the final EBSs and stimulus-PV intervals.
RESULTS: For Lt.PVs, the stimulus-PV intervals during CSd pacing were
significantly shorter than during HRA pacing at the Lt.PV anterior carina and
bottom (90+/-28 ms vs. 125+/-26 ms, P<0.001 and 84+/-20 ms vs. 148+/-24 ms,
P=0.028, respectively), but there was no significant difference in the Lt.PV roof
and any posterior segments. For Rt.PVs, the stimulus-PV interval from both pacing
sites exhibited no significant difference between either segment. CONCLUSIONS:
This pacing method may help to identify whether EBSs are located in the anterior
Lt.PVs. Improved recognition of EBSs through pacing from different sites would be
helpful for achieving PV isolation.
PMID- 28416974
TI - Major determinants for the selecting antithrombotic therapies in patients with
nonvalvular atrial fibrillation in Japan (JAPAF study).
AB - BACKGROUND: Oral anticoagulants (OACs) can help prevent stroke in patients with
nonvalvular atrial fibrillation (NVAF). The aim of this study was to characterize
the use of OACs other than direct thrombin inhibitors (DTIs) for NVAF. METHODS:
Patients with NVAF taking antithrombotics other than DTIs were enrolled in this
cross-sectional study. Patient demographics and medication history were
collected, and the patients were classified as taking antiplatelet monotherapy
(AP), anticoagulant monotherapy (AC), or combination therapy (AP+AC). OAC users
were also stratified as naive (N; initiated within 6 months), switcher (S;
switched within 6 months), or prevalent user (P; continued for >6 months).
RESULTS: A total of 3053 patients (AP, 216; AC, 2381; AP+AC, 456) from 268 sites
were enrolled from 2012 to 2013. Significant differences were observed in CHADS2
scores (AP/AC/AP+AC: 2.0/2.1/2.7, P<0.0001), angina complications (20.1/8.6/32.1,
P<0.0001), myocardial infarction (5.1/2.8/18.1, P<0.0001), prothrombin time
international normalized ratio (PT-INR) (-/2.00/1.94, P=0.0350), and others.
There were 2831 OAC users (N, 328; S, 213; P, 2290). Significant differences were
observed in history of bleeding (N/S/P: 2.4/9.4/4.5, P<0.001), PT-INR
(1.83/2.01/2.00, P<0.0001), and others. CONCLUSIONS: Patients taking AP+AC had
higher CHADS2 scores than those taking an AP or AC alone. Additionally, the
combination therapy (AP+AC) was preferred in patients with cardiovascular
comorbidity. Changes in AC regimens were not influenced by CHADS2 scores or
complications but influenced by history of bleeding. These characteristics were
thus identified as major factors affecting the selection of antithrombotic
regimens other than DTIs in patients with NVAF.
PMID- 28416975
TI - Effectiveness and safety of dabigatran versus warfarin in "real-world" Japanese
patients with atrial fibrillation: A single-center observational study.
AB - BACKGROUND: In "real-world" practice, anticoagulant therapy is indicated for
patients whose clinical profiles are not addressed in randomized clinical trials.
We assessed the effectiveness and safety of dabigatran versus warfarin in "real
world" Japanese patients with non-valvular atrial fibrillation (NVAF). METHODS:
Among 613 NVAF patients who initiated dabigatran or warfarin therapy during the
period between 2011 and 2013, 362 patients were included in the study after
propensity score adjustment. The median follow-up period was 1.3 years. The
effectiveness and safety outcomes were thromboembolism and major bleeding,
respectively. RESULTS: The propensity-matched hazard ratios of thromboembolism
and major bleeding with dabigatran were 1.03 (95% CI: 0.12-8.04, p=0.971) and
0.15 (95% CI: 0.01-0.90, p=0.037), respectively. CONCLUSIONS: The ability of
dabigatran to prevent thromboembolism is comparable to that of warfarin; however,
the major bleeding rate is lower with dabigatran in "real-world" NVAF patients.
PMID- 28416977
TI - Trends in physiological coagulation factors in Japanese patients receiving novel
oral anticoagulants.
AB - BACKGROUND: Little is known about physiological anticoagulation effects via
antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral
anticoagulants (NOACs). METHODS: We evaluated 120 consecutive patients with non
valvular atrial fibrillation (AF) receiving NOACs. Patients were randomly divided
into three groups: a dabigatran group (DG, N=40), a rivaroxaban group (RG, N=40)
or an apixaban group (AG, N=40). A warfarin group (WG, N=40) was matched with
NOAC groups for age, sex and type of AF during the same time period. Blood
samples were obtained in pretreatment, trough and peak phases to measure the
activity of physiological coagulation inhibitors, including AT III and PC/PS or
thrombus formation markers such as D-dimer and thrombin-antithrombin complex
(TAT). RESULTS: D-dimer, TAT and AT III values for the NOAC groups were
equivalent in the peak and trough phases. PC/PS activity in both phases was
equally maintained in the pretreatment phase in the NOAC groups, while the
activity in the WG was significantly suppressed in steady state. Moreover, no
differences in trends for PC/PS activity were observed among NOAC groups.
CONCLUSIONS: PC/PS activity was constant in both peak and trough phases in the
patients on NOACs compared with activity of those on warfarin. In addition, there
was no difference in the findings among NOACs.
PMID- 28416976
TI - Rationale and design of ASSAF-K (A study of the safety and efficacy of
anticoagulant therapy in the treatment of atrial fibrillation in Kanagawa).
AB - BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent cardiac
arrhythmias associated with substantially increased risks of ischemic stroke and
thromboembolism. Oral anticoagulants (OACs) are the cornerstone of AF management
and effectively prevent AF-related stroke. As new non-vitamin K antagonist OACs
(NOACs) have become available, the landscape of stroke prevention in AF has
changed. However, there are considerable gaps between daily clinical practice and
current guideline-based recommendations for anticoagulant therapy in Japan.
Consequently, little is known about the real-world setting and the current use of
NOACs, especially by practitioners in Japan. METHODS: We conducted a prospective,
observational study in 3847 patients with AF who were enrolled in clinics and
hospitals located in Kanagawa Prefecture from September 2013 through March 2015.
The participating centers included practitioners (small clinics), medium-sized
hospitals, and university hospitals. The primary endpoints were epidemiologic
characteristics, status of treatment with anticoagulants and antiplatelet agents,
outcomes, and adverse events, including cerebrovascular disease, bleeding, and
death. RESULTS: The mean CHADS2 score was 1.81+/-1.27, the mean CHADS2-Vasc score
was 3.02+/-1.58, and the mean HAS-BLED score was 2.23+/-1.06, respectively. The
usage rate of warfarin was 44.2% overall, and the usage rate of NOACs was 33.5%.
CONCLUSIONS: The results of the study are expected to serve as the basis for
providing clinical practice guidance to healthcare institutions in Japan, with
the ultimate goals of better characterizing the appropriate use of OACs and
providing clinical decision support to physicians to facilitate the design of
appropriate therapeutic strategies and the selection of anticoagulants for the
management of AF.
PMID- 28416978
TI - Atrial electromechanical delay in patients undergoing heart transplantation.
AB - BACKGROUND: We aimed to assess atrial electromechanical delay (AEMD) in patients
who had undergone heart transplantation. METHODS: A total of 32 patients who
underwent biatrial anastomosis heart transplantation (24 men, 8 women; mean age:
42+/-11 years) and 30 healthy volunteers (20 men, 10 women; mean age: 36+/-13
years) were included in the study. Atrial electromechanical coupling (PA), intra
AEMD, and inter-AEMD were measured. RESULTS: PA lateral (68+/-7 vs. 51+/-11 ms,
p<0.01), PA septal (50+/-5 vs. 42+/-8 ms, p< 0.01) and PA tricuspid (39+/-6 vs.
36+/-9 ms, p<0.01), inter-AEMD (PA lateral-PA tricuspid) (27+/-7 vs. 10+/-4 ms,
p<0.01), left intra-AEMD (PA lateral-PA septal) (18+/-7 vs. 10+/-4 ms, p<0.01),
right intra-AEMD (PA septal-PA tricuspid) (13+/-5 vs. 5+/-3 ms, p<0.01) values
were higher in patients who underwent heart transplantation than in a control
population. CONCLUSION: Inter-AEMD and intra-AEMD were prolonged in patients who
underwent heart transplantation as compared to a control population. This may
explain the increased atrial fibrillation and other atrial arrhythmia incidences
associated with the biatrial anastomosis heart transplantation technique and may
contribute to the treatment of atrial fibrillation in this special patient group.
PMID- 28416979
TI - Comparison of hemodynamic effects of biventricular versus left ventricular only
pacing in patients receiving cardiac resynchronization therapy: A before-after
clinical trial.
AB - BACKGROUND: Biventricular (BiV) pacing is the most common mode of delivering
cardiac resynchronization therapy (CRT). However, initial clinical studies have
indicated that left ventricular (LV) pacing is not inferior to BiV pacing. This
study was conducted to address whether LV only pacing can provide the same
hemodynamic response as BiV pacing. METHODS: This before-after clinical trial was
conducted at Ekbatan Hospital, from July 2012 to November 2014. Patients with a
LV ejection fraction <=35% and a QRS duration >=0.12 s who had a standard
indication for ventricular pacing were enrolled. The CRT devices of all patients
had already been set for BiV pacing. Therefore, their CRT devices were set for LV
only pacing for 3 months. The hemodynamic status of the patients was assessed by
echocardiography before setting the CRT device to LV only pacing (as a control)
and 3 months after (as an intervention). RESULTS: There was no statistically
significant difference between the effect of BiV pacing and LV only pacing on the
hemodynamic responses including LV ejection fraction, LV end diastolic and
systolic volume, and velocity time integral of the aortic valve. Moreover, no
significant difference was seen between men and women either. CONCLUSIONS: LV
only pacing is not inferior to BiV pacing, and the hemodynamic response was
similar in the two groups. However, the LV mode has a number of advantages over
the BiV mode. More evidence, based on large clinical trials, is needed to confirm
our results.
PMID- 28416980
TI - Comparison of the measured pre-ejection periods and left ventricular ejection
times between echocardiography and impedance cardiography for optimizing cardiac
resynchronization therapy.
AB - BACKGROUND: The pre-ejection period (PEP) and left ventricular ejection time
(LVET) are easily measured by impedance cardiography (ICG). We hypothesized that
the PEP/LVET measured by ICG would correlate with that measured by
echocardiography, and that PEP/LVET measured by ICG would be useful for cardiac
resynchronization therapy (CRT) optimization. METHODS: Newly CRT implanted
patients were optimized by echocardiography. The PEP/LVET was measured by
echocardiography and ICG in two different settings: optimized setting and right
ventricle (RV)-only pacing. RESULTS: The PEP/LVET was significantly decreased in
the optimized setting compared with that in RV-only pacing (0.62+/-0.13 vs 0.75+/
0.16, p<0.05). The PEP/LVET values calculated by ICG and echocardiography were
positively correlated (r=0.553, p=0.003). CONCLUSION: ICG was useful for the
optimization of CRT.
PMID- 28416981
TI - Relationship between right and left ventricular function in candidates for
implantable cardioverter defibrillator with low left ventricular ejection
fraction.
AB - BACKGROUND: Indications for the primary prevention of sudden death using an
implantable cardioverter defibrillator (ICD) are based predominantly on left
ventricular ejection fraction (LVEF). However, right ventricular ejection
fraction (RVEF) is also a known prognostic factor in a variety of structural
heart diseases that predispose to sudden cardiac death. We sought to investigate
the relationship between right and left ventricular parameters (function and
volume) measured by cardiovascular magnetic resonance (CMR) among a broad
spectrum of patients considered for an ICD. METHODS: In this retrospective,
single tertiary-care center study, consecutive patients considered for ICD
implantation who were referred for LVEF assessment by CMR were included. Right
and left ventricular function and volumes were measured. RESULTS: In total, 102
patients (age 62+/-14 years; 23% women) had a mean LVEF of 28+/-11% and RVEF of
44+/-12%. The left ventricular and right ventricular end diastolic volume index
was 140+/-42 mL/m2 and 81+/-27 mL/m2, respectively. Eighty-six (84%) patients had
a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction.
Although there was a significant and moderate correlation between LVEF and RVEF
(r=0.40, p<0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF,
while 9 of 16 patients (56%) with LVEF >=35% had right ventricular systolic
dysfunction (Kappa=0.041). CONCLUSIONS: Among patients being considered for an
ICD, there is a positive but moderate correlation between LVEF and RVEF. A
considerable proportion of patients who qualify for an ICD based on low LVEF have
preserved RVEF, and vice versa.
PMID- 28416982
TI - Automatic atrial capture device control in real-life practice: A multicenter
experience.
AB - BACKGROUND: Device-based fully automatic pacing capture detection is useful in
clinical practice and important in the era of remote care management. The main
objective of this study was to verify the effectiveness of the new ACAP
Confirm(r) algorithm in managing atrial capture in the medium term in comparison
with early post-implantation testing. METHODS: Data were collected from 318
patients (66% male; mean age, 73+/-10 years); 237 of these patients underwent
device implantation and 81 box changes in 31 Italian hospitals. Atrial threshold
measurements were taken manually and automatically at different pulse widths
before discharge and during follow-up (7+/-2 months) examination. RESULTS: The
algorithm worked as expected in 73% of cases, considering all performed tests.
The success rate was 65% and 88% pre-discharge and during follow-up examination
(p<0.001), respectively, in patients who had undergone implantation. We did not
detect any difference in the performance of the algorithm as a result of the type
of atrial lead used. The success rate was 70% during pre-discharge testing in
patients undergoing device replacement. Considering all examination types, manual
and automatic measurements yielded threshold values of 1.07+/-0.47 V and 1.03+/
0.47 V at 0.2-ms pulse duration (p=0.37); 0.66+/-0.37 V and 0.67+/-0.36 V at 0.4
ms (p=0.42); and 0.5+/-0.28 V and 0.5+/-0.29 V at 1 ms (p=0.32). CONCLUSIONS: The
results show that the algorithm works before discharge, and its reliability
increases over the medium term. The algorithm also proved accurate in detecting
the atrial threshold automatically. The possibility of activating it does not
seem to be influenced by the lead type used, but by the time from implantation.
PMID- 28416984
TI - The inferior displacement of the His bundle and fast pathway in a patient with
common type atrioventricular nodal tachycardia: Three-dimensional computed
tomography analysis.
AB - A 66-year-old woman with palpitations was referred to our center for catheter
ablation due to drug-refractory, common type atrioventricular nodal tachycardia
(AVNRT). A selective slow pathway ablation was attempted. A fast junctional
rhythm with transient ventriculoatrial block followed by transient prolongation
of the A-H interval occurred immediately after the radiofrequency (RF)
application at the coronary sinus ostium (CSOS) level. To assess the location of
the fast pathway and His bundle, we sought to visualize the anatomy of the
triangle of Koch (TOK) by three-dimensional computed tomography (CT).
PMID- 28416983
TI - Local conduction during acute myocardial infarction in rats: Interplay between
central sympathetic activation and endothelin.
AB - We investigated the effects of autonomic dysfunction and endothelin on local
conduction and arrhythmogenesis during myocardial infarction. We recorded
ventricular tachyarrhythmias, monophasic action potentials, and activation
sequences in wild-type and ETB-deficient rats displaying high endothelin levels.
Central sympathetic inputs were examined after clonidine administration.
Clonidine mitigated early and delayed arrhythmogenesis in ETB-deficient and wild
type rats, respectively. The right ventricular activation delay increased in
clonidine-treated ETB-deficient rats and slightly decreased in wild-type rats.
The left ventricular voltage rise decreased in all groups, whereas the activation
delay increased mainly in clonidine-treated ETB-deficient rats. Central
sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis.
Ischemia alters excitability, whereas endothelin impairs local conduction, an
action partly counterbalanced by central sympathetic activity.
PMID- 28416985
TI - Successful pacemaker lead extraction involving an ossified thrombus: A case
report.
AB - A 41-year-old woman who had been fitted with a pacemaker 18 years prior presented
for lead extraction because of device infection. First, we tried laser sheath.
However, it cannot cross the binding in the innominate vein. Then we switched to
the rotating mechanical sheath. Although it crunched through binding tissue, the
progress halted. We removed the sheath and found pieces of calcified tissue in
the sheath lumen. After removing the calcified tissue, both leads were extracted
using the laser sheath, without complications. The pathological examination
revealed a diagnosis of ossified thrombus. Venous thromboses associated with
implanted leads can ossify with time, causing difficulties in the extraction of
long-standing intravascular leads.
PMID- 28416986
TI - Two cases of inappropriate implantable cardioverter-defibrillator therapies due
to T wave oversensing induced by body twisting.
AB - T wave oversensing (TWOS) is a common cause of inappropriate implantable
cardioverter-defibrillator (ICD) therapies. Various algorithms to avoid
inappropriate ICD therapy are available; however, they are not helpful to avoid
TWOS. Although the reproduction of TWOS is useful to resolve the problem of TWOS,
it is sometimes difficult to reproduce TWOS. We report two cases of inappropriate
ICD therapy due to TWOS, which were induced only by body twisting. We can
successfully manage the device based on the evidence of reproduced TWOS.
PMID- 28416987
TI - Importance of exercise testing shortly after subcutaneous implantable
cardioverter-defibrillator implantation in patients with Brugada syndrome - The
first case of associated inappropriate shock in Japan.
AB - We report the case of a 51-year-old patient with Brugada syndrome (BrS) who
experienced inappropriate shock due to T-wave oversensing (TWOS) during exercise
when the optimal sensing vector was selected based on the automatic analysis by a
subcutaneous implantable cardioverter-defibrillator (S-ICD). After selecting
another vector during exercise testing, TWOS did not re-occur. Selection of
appropriate sensing vector based on analyses under various conditions, including
during exercise after S-ICD implantation, should be considered for patients with
BrS.
PMID- 28416988
TI - Loss of atrial pacing in a patient with a dual-chamber permanent pacemaker: What
is the mechanism?
PMID- 28416989
TI - Immediate Breast Reconstruction of a Nipple Areolar Lumpectomy Defect With the L
Flap Skin Paddle Breast Reduction Design and Contralateral Reduction Mammoplasty
Symmetry Procedure: Optimizing the Oncoplastic Surgery Multispecialty Approach.
AB - Objective: We describe a modification of the inferior pedicle reduction
mammoplasty for oncoplastic reconstruction of a central tumor defect. Our
technique involved a deepithelialized L-shaped medial inferior based flap with
removal of lateral breast tissue after central lumpectomy with a contralateral
Wise-pattern mastopexy with inferior pedicle for symmetry. This technique is
ideal for patients with large, ptotic breasts that desire breast conservation
with immediate reconstruction. Methods: A 47-year-old woman with size 38 DD
breasts presented with a palpable 2-cm subareolar mass of the left breast.
Surgical oncology performed a left lumpectomy with nipple-areola complex excision
and a sentinel lymph node biopsy. Immediate left breast reconstruction was
performed with an inferior pedicle island flap. An additional 30 g of breast
tissue was excised laterally for contour, and the neo-nipple-areola complex was
rotated into the defect to facilitate inverted-T closure. A standard Wise-pattern
mastopexy with inferior pedicle was then performed on the right breast and an
additional 205 g of tissue was removed for symmetry. Results: The patient showed
excellent symmetry at the conclusion of the procedure. Final pathology
demonstrated complete excision of the tumor with negative margins. The entire neo
nipple-areola complex skin island was viable postoperatively. Conclusions:
Immediate reconstruction of a nipple-areola complex lumpectomy defect with a L
shaped medial inferior based skin paddle flap and contralateral reduction
mammoplasty provides an excellent cosmetic outcome in patients with large, ptotic
breasts and central defects following oncologic tumor resection.
PMID- 28416990
TI - Medications for osteoporotic pain.
PMID- 28416991
TI - Can denosumab be a substitute, competitor, or complement to bisphosphonates?
AB - Osteoblasts, originating from mesenchymal cells, make the receptor activator of
the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to
control differentiation of activated osteoclasts, originating from hematopoietic
stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature
osteoclasts, bone resorption increases. On the contrary, when OPG binds to the
RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy
receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL
resulting in inhibition of osteoclastogenesis and reduction of bone resorption.
Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of
resorption performed by activated osteoclasts, are still the drugs of choice to
prevent and treat osteoporosis. The merits of denosumab are reversibility
targeting the RANKL, lack of adverse gastrointestinal events, improved adherence
due to convenient biannual subcutaneous administration, and potential use with
impaired renal function. The known adverse reactions are musculoskeletal pain,
increased infections with adverse dermatologic reactions, osteonecrosis of the
jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of
denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3
days, with maximum reduction occurring by 1 month. The mean time to maximum
denosumab concentration is 10 days with a mean half-life of 25.4 days. In
conclusion, the convenient biannual subcutaneous administration of 60 mg of
denosumab can be considered as a first-line treatment for osteoporosis in cases
of low compliance with BPs due to gastrointestinal trouble and impaired renal
function.
PMID- 28416992
TI - Sphenopalatine ganglion block for relieving postdural puncture headache:
technique and mechanism of action of block with a narrative review of efficacy.
AB - The sphenopalatine ganglion (SPG) is a parasympathetic ganglion, located in the
pterygopalatine fossa. The SPG block has been used for a long time for treating
headaches of varying etiologies. For anesthesiologists, treating postdural
puncture headaches (PDPH) has always been challenging. The epidural block patch
(EBP) was the only option until researchers explored the role of the SPG block as
a relatively simple and effective way to treat PDPH. Also, since the existing
evidence proving the efficacy of the SPG block in PDPH is scarce, the block
cannot be offered to all patients. EBP can be still considered if an SPG block is
not able to alleviate pain due to PDPH.
PMID- 28416993
TI - Antinociceptive effect of intrathecal sec-O-glucosylhamaudol on the formalin
induced pain in rats.
AB - BACKGROUND: The root of Peucedanum japonicum Thunb., a perennial herb found in
Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous
study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was
performed to examine the antinociceptive effect of intrathecal SOG in the
formalin test. METHODS: Male Sprague-Dawley rats were implanted with an
intrathecal catheter. Rats were randomly treated with a vehicle and SOG (10 ug,
30 ug, 60 ug, and 100 ug) before formalin injection. Five percent formalin was
injected into the hind-paw, and a biphasic reaction followed, consisting of
flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Naloxone
was injected 10 min before administration of SOG 100 ug to evaluate the
involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values
were calculated. RESULTS: Intrathecal SOG showed a significant reduction of the
flinching responses at both phases in a dose-dependent manner. Significant
effects were showed from the dose of 30 ug and maximum effects were achieved at a
dose of 100 ug in both phases. The ED50 value (95% confidence intervals) of
intrathecal SOG was 30.3 (25.8-35.5) ug during phase 1, and 48.0 (41.4-55.7)
during phase 2. The antinociceptive effects of SOG (100 ug) were significantly
reverted at both phases of the formalin test by naloxone. CONCLUSIONS: These
results demonstrate that intrathecal SOG has a very strong antinociceptive effect
in the formalin test and it seems the effect is related to an opioid receptor.
PMID- 28416994
TI - The radiation safety education and the pain physicians' efforts to reduce
radiation exposure.
AB - BACKGROUND: C-arm fluoroscopy equipment is important for interventional pain
management and can cause radiation injury to physicians and patients. We compared
radiation safety education and efforts to reduce the radiation exposure of pain
specialists. METHODS: A survey of 49 pain specialists was conducted anonymously
in 2016. The questionnaire had 16 questions. That questionnaire was about
radiation safety knowledge and efforts to reduce exposure. We investigated the
correlation between radiation safety education and efforts of radiation
protection. We compared the results from 2016 and a published survey from 2011.
RESULTS: According to the 2016 survey, all respondents used C-arm fluoroscopy in
pain interventions. Nineteen respondents (39%) had received radiation safety
education. Physicians had insufficient knowledge about radiation safety. When the
radiation safety education group and the non-education group are compared, there
was no significant difference in efforts to reduce radiation exposure and
radiation safety knowledge. When the 2011 and 2016 surveys were compared, the use
of low dose mode (P = 0.000) and pulsed mode had increased significantly (P =
0.001). The number checking for damage to radiation protective garments (P =
0.000) and use of the dosimeter had also increased significantly (P = 0.009). But
there was no significant difference in other efforts to reduce radiation
exposure. CONCLUSIONS: Pain physicians seem to lack knowledge of radiation safety
and the number of physicians receiving radiation safety education is low.
According to this study, education does not lead to practice. Therefore, pain
physicians should receive regular radiation safety education and the education
should be mandatory.
PMID- 28416995
TI - Sufficient explanation of management affects patient satisfaction and the
practice of post-treatment management in spinal pain, a multicenter study of 1007
patients.
AB - BACKGROUND: Spinal pain is most common symptom in pain clinic. In most cases,
before the treatment of spinal pain, physician explains the patient's disease and
treatment. We investigated patient's satisfaction and physician's explanation
related to treatments in spinal pain patients by questionnaires. METHODS:
Anonymous questionnaires about physician's explanation and patient's satisfaction
in each treatment and post-treatment management were asked to individuals
suffering from spinal pain. Patients who have spinal pain were participated in
our survey of nationwide university hospitals in Korea. The relationships between
patient's satisfaction and other factors were analyzed. RESULTS: Between June
2016 and August 2016, 1007 patients in 37 university hospitals completed the
questionnaire. In the statistical analysis, patient's satisfaction of treatment
increased when pain severity was low or received sufficient preceding explanation
about nerve block and medication (P < 0.01). Sufficient explanation increased
patient's necessity of a post-treatment management and patients' performance rate
of post-treatment management (P < 0.01). CONCLUSIONS: These results show that
sufficient explanation increased patients' satisfaction after nerve block and
medication. Sufficient explanation also increased the practice of patients' post
treatment management.
PMID- 28416996
TI - The relationship between the development of musculoskeletal disorders, body mass
index, and academic stress in Bahraini University students.
AB - BACKGROUND: There are many mechanisms in which stress can lead to weight gain
thus high a BMI. The endocrine and inflammatory pathway can directly increase
abdominal adiposity. Another way in which stress leads to weight gain is through
changes in health behaviors. The study aimed to investigate the prevalence of
musculoskeletal disorders (MSDs) among healthy students of Ahlia University, and
to determine the relationship between the development of MSDs and academic
stressors and body mass index. METHODS: Self-administered questionnaires were
distributed to 94 students aged 18-26 years who were enrolled at various Ahlia
University colleges and met other inclusion criteria. The students responded to
the standardized Nordic musculoskeletal questionnaire and the modified College
Student Stress Inventory regarding musculoskeletal symptoms and academic
stressors. Height and weight measurements were also obtained to determine body
mass index. RESULTS: A total of 77.66% reported MSDs in one or more body part,
with the prevalence being higher among women than among men. The 7-day prevalence
of MSDs severe enough to interfere with activities of daily living was 60.64%,
and 44.68% by female and male students, respectively. There was a significant
relationship between academic stress and MSDs in the neck, shoulders, lower back,
and hips, while the relationship between MSDs, and body mass index, academic
stress, and grade point average was not significant. CONCLUSIONS: The prevalence
of MSDs among Ahlia University students was found to be high. Apart from the
positive correlation between academic stress and MSDs in certain body parts,
other correlations were not significant.
PMID- 28416997
TI - Comparison of intrathecal versus intra-articular dexmedetomidine as an adjuvant
to bupivacaine on postoperative pain following knee arthroscopy: a randomized
clinical trial.
AB - BACKGROUND: Postoperative pain is a common, distressing symptom following
arthroscopic knee surgery. The aim of this study was to compare the potential
analgesic effect of dexmedetomidine after intrathecal versus intra-articular
administration following arthroscopic knee surgery. METHODS: Ninety patients
undergoing unilateral elective arthroscopic knee surgery were randomly assigned
into three groups in a double-blind placebo controlled study. The intrathecal
dexmedetomidine group (IT) received an intrathecal block with intrathecal
dexmedetomidine, the intra-articular group (IA) received an intrathecal block and
intra-articular dexmedetomidine, and the control group received an intrathecal
block and intra-articular saline. The primary outcome of our study was
postoperative pain as assessed by the visual analogue scale of pain (VAS).
Secondary outcomes included the effect of dexmedetomidine on total postoperative
analgesic use and time to the first analgesic request, hemodynamics, sedation,
postoperative nausea and vomiting, patient satisfaction, and postoperative C
reactive protein (CRP) levels. RESULTS: Dexmedetomidine administration decreased
pain scores for 4 h in both the intrathecal and intra-articular groups, compared
to only 2 h in the control patient group. Furthermore, there was a significant
reduction in pain scores for 6 h in the intra-articular group. The time to the
first postoperative analgesia request was longer in the intra-articular group
compared to the intrathecal and control groups. The total meperidine requirement
was significantly lower in the intra-articular and intrathecal groups than in the
control group. CONCLUSIONS: Both intrathecal and intra-articular dexmedetomidine
enhanced postoperative analgesia after arthroscopic knee surgery. Less total
meperidine was required with intra-articular administration to extend
postoperative analgesia to 6 h with hemodynamic stability.
PMID- 28416998
TI - Prevalence and trends of pain associated with chronic diseases and personal out
of-pocket medical expenditures in Korea.
AB - BACKGROUND: There have been few studies about pain using a big data. The purpose
of this study was to identify the prevalence of pain, and trends of pain
associated with chronic diseases and personal out-of-pocket medical expenditures
over time. METHODS: Subjects were 58,151 individuals, using the Korea Health
Panel from 2009 to 2013. Chi-square and multinomial logistic regression were
conducted to identify the prevalence and odds ratios (ORs) of pain. Repeated
measures ANOVA was used to find the trend over these 5 years. RESULTS: Prevalence
of mild and severe pain was 28.1% and 1.7% respectively. The ORs of mild and
severe pain were 1.6 and 1.4 in females compared with males. From 2009 to 2013,
numbers of chronic diseases producing mild pain were 2.1, 2.4, 2.8, 2.9, and 3.1
and those producing severe pain were 3.0, 3.4, 3.9, 4.2, and 4.4, respectively.
After applying the average South Korean inflation rate by year over 5 years, the
annual, personal out-of-pocket medical expenditures (unit: ?1,000) for mild pain
were 322, 349, 379, 420, and 461, and those for severe pain were 331, 399, 504,
546, and 569, respectively (P < 0.0001). CONCLUSIONS: The pain prevalence was
29.8%. The numbers of chronic diseases and the personal out-of-pocket medical
expenditures revealed increasing trends annually, especially in those with pain.
Therefore, to eliminate and alleviate the pain, there needs to be further study
for developing a systemic approach.
PMID- 28416999
TI - Bilateral maxillary and mandibular buccal exostosis: a self reported case and a
proposal to include buccal exostosis under miscellaneous disorders of revised
working classification of the psychosomatic disorders pertaining to dental
practice.
PMID- 28417000
TI - hackseq: Catalyzing collaboration between biological and computational scientists
via hackathon.
AB - hackseq ( http://www.hackseq.com) was a genomics hackathon with the aim of
bringing together a diverse set of biological and computational scientists to
work on collaborative bioinformatics projects. In October 2016, 66 participants
from nine nations came together for three days for hackseq and collaborated on
nine projects ranging from data visualization to algorithm development. The
response from participants was overwhelmingly positive with 100% (n = 54) of
survey respondents saying they would like to participate in future hackathons. We
detail key steps for others interested in organizing a successful hackathon and
report excerpts from each project.
PMID- 28417001
TI - Minimally invasive esophagectomy for esophageal cancer according to the location
of the tumor: Experience of 251 patients.
AB - BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly used for the
treatment of esophageal cancer. However, the ideal approach of MIE is not yet
standardized. We explore the ideal approach of MIE according to the location of
the tumor and compare the clinical outcomes between patients with cancer arising
in the upper third of the esophagus and those with tumors involving the middle
and lower third of the esophagus. METHODS: We included patients with esophageal
carcinoma and had clear indications for MIE. For cancer arising in the upper
third of the esophagus, MIE McKeown approach was performed. For tumors involving
the middle and lower third of the esophagus, MIE Ivor Lewis approach was adopted.
RESULTS: Of the 251 patients included in this analysis, 200 patients underwent
Ivor-Lewis MIE and 51 patients underwent McKeown MIE. The incidence of
anastomotic leak, anastomotic stenosis and recurrent laryngeal nerve injury was
significantly higher in the McKeown MIE group than that in the Ivor Lewis MIE
group. The 30-day postoperative mortality rate was 1.2% (n = 1) in the McKeown
MIE group. Lymph nodes harvested were significantly more in the MIE-McKeown group
than in Ivor Lewis MIE group (P < 0.05). The median follow-up period was 15
months (1-25 months) and the overall survival rate at 1 year stratified by
pathologic stage at esophagectomy was 95.9% (stage 1), 83.8% (stage II), 73.4%
(stage III). CONCLUSIONS: MIE for esophageal cancer according to the location and
clinical stage of the tumor will decrease all postoperative complications and may
yield the greatest benefit from surgery.
PMID- 28417002
TI - Motivation to change, coping, and self-esteem in adolescent anorexia nervosa: a
validation study of the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ).
AB - BACKGROUND: Understanding motivation to change is a key issue in both the
assessment and the treatment of eating disorders. Therefore, sound instruments
assessing this construct are of great help to clinicians. Accordingly, the
present study analysed the psychometric properties of the Anorexia Nervosa Stages
of Change Questionnaire (ANSOCQ), including its relation to coping style and self
esteem. METHODS: N = 92 adolescents referred to an eating disorders outpatient
clinic meeting criteria for anorexia nervosa gave written informed consent to
participate in this study and completed the ANSOCQ, the Eating Disorder
Inventory, the Eating Attitudes Test, the Body Image Questionnaire, two
questionnaires measuring Self-Related Cognitions and the Coping Across Situations
Questionnaire. After a treatment period of nine months, clinical anorexia nervosa
diagnosis and the body mass index were re-assessed. In addition to exploratory
factor analysis, correlational analysis was used to test for the convergent
validity of the ANSOCQ and logistic regression analysis was used to test its
predictive validity. RESULTS: The ANSOCQ had good psychometric properties. Factor
analysis yielded two meaningful factors labelled as 'weight gain and control' and
'attitudes and feelings'. Internal consistencies of the two factors amounted to
Cronbach's alpha = .87 and .76, respectively. Significant correlations with other
scales measuring eating disorder psychopathology were indicative of meaningful
construct validity. Higher motivation to change was related to higher self-esteem
and a more active coping style. Higher (positive) ANSOCQ total scores predicted
remission of anorexia nervosa after nine months of treatment. A higher score on
'attitudes and feelings' was a protective factor against drop-out from
intervention. CONCLUSIONS: The ANSOCQ is a clinically useful instrument for
measuring motivation to change in adolescents with AN. Two factorial dimensions
explain most of the variation. Self-esteem and coping style are relevant
additional constructs for the understanding of the motivation to change in
anorexia nervosa. TRIAL REGISTRATION: NCT02828956. Retrospectively registered
July 2016.
PMID- 28417004
TI - The effect of relatedness and pack size on territory overlap in African wild
dogs.
AB - BACKGROUND: Spacing patterns mediate competitive interactions between
conspecifics, ultimately increasing fitness. The degree of territorial overlap
between neighbouring African wild dog (Lycaon pictus) packs varies greatly, yet
the role of factors potentially affecting the degree of overlap, such as
relatedness and pack size, remain unclear. We used movement data from 21 wild dog
packs to calculate the extent of territory overlap (20 dyads). RESULTS: On
average, unrelated neighbouring packs had low levels of overlap restricted to the
peripheral regions of their 95% utilisation kernels. Related neighbours had
significantly greater levels of peripheral overlap. Only one unrelated dyad
included overlap between 75%-75% kernels, but no 50%-50% kernels overlapped.
However, eight of 12 related dyads overlapped between their respective 75%
kernels and six between the frequented 50% kernels. Overlap between these more
frequented kernels confers a heightened likelihood of encounter, as the mean
utilisation intensity per unit area within the 50% kernels was 4.93 times greater
than in the 95% kernels, and 2.34 times greater than in the 75% kernels. Related
packs spent significantly more time in their 95% kernel overlap zones than did
unrelated packs. Pack size appeared to have little effect on overlap between
related dyads, yet among unrelated neighbours larger packs tended to overlap more
onto smaller packs' territories. However, the true effect is unclear given that
the model's confidence intervals overlapped zero. CONCLUSIONS: Evidence suggests
that costly intraspecific aggression is greatly reduced between related packs.
Consequently, the tendency for dispersing individuals to establish territories
alongside relatives, where intensively utilised portions of ranges regularly
overlap, may extend kin selection and inclusive fitness benefits from the intra
pack to inter-pack level. This natural spacing system can affect survival
parameters and the carrying capacity of protected areas, having important
management implications for intensively managed populations of this endangered
species.
PMID- 28417003
TI - Migration distance as a selective episode for wing morphology in a migratory
insect.
AB - BACKGROUND: Selective pressures that occur during long-distance migration can
influence morphological traits across a range of taxa. In flying insects,
selection should favour individuals that have wing morphologies that increase
energy efficiency and survival. In monarch butterflies, differences in wing
morphology between migratory and resident populations suggest that migratory
populations have undergone selection for larger (as measured by length and area)
and more elongated (as measured by roundness and aspect ratio) forewings.
However, selection on wing morphology may also occur within migratory
populations, particularly if individuals or populations consistently migrate
different distances. RESULTS: Using 613 monarch butterflies that were collected
on the Mexican wintering grounds between 1976 - 2014, we tested whether monarch
wing traits were associated with migratory distance from their natal areas in
eastern North America (migration range: 774-4430 km), as inferred by stable
hydrogen (delta2H) and -carbon (delta13C) isotopic measurements. Monarchs that
migrated farther distances to reach their overwintering sites tended to have
longer and larger wings, suggesting positive selective pressure during migration
on wing length and area. There was no relationship between migration distances
and either roundness or aspect ratio. CONCLUSIONS: Our results provide
correlative evidence that the migratory period may act as a selective episode on
monarch butterfly wing morphology, although selection during other portions of
the annual cycle, as well as extensive mixing of individuals from various natal
locations on the breeding grounds, likely counteracts directional selection of
migration on morphology.
PMID- 28417005
TI - Reversibility of VasalgelTM male contraceptive in a rabbit model.
AB - BACKGROUND: Development of a non-hormonal long-acting reversible contraceptive
for men could have a significant impact on reducing unintended pregnancies.
VasalgelTM is a high molecular weight polymer consisting of styrene-alt-maleic
acid (SMA) dissolved in dimethyl sulfoxide being developed as a reversible male
contraceptive device. It forms a hydrogel when implanted into the vasa
deferentia, which prevents the passage of sperm. Previous studies in the rabbit
have proven its efficacy, durability and rapid onset. This study evaluates the
capacity to restore sperm concentrations in ejaculates after a reversal
procedure. METHODS: Sodium bicarbonate was injected into the vasa deferentia
after fourteen months of azoospermia following the injection of two device
variations (Vasalgel 100 and Vasalgel 80). Semen samples were then collected for
six months and sperm characteristics were compared to baseline levels. Samples of
vasa deferentia were obtained for histological examination. RESULTS: Spermatozoa
were present in all subject ejaculates after the reversal procedure. Sperm
concentration and sperm motility were similar to baseline levels after reversal,
while sperm forward progression was significantly lower and normal acrosomes were
not observed. Forward progression percentages increased linearly during six
months of semen collection, however, normal acrosomes were not observed at the
conclusion of the study. Histologically, several vasa deferentia were clear of
the device and contained an intact epithelial lining. A smaller proportion of
tissues contained residual test material. A secondary intraluminal inflammatory
response was seen occasionally in the tissues containing residual material. There
was no difference between the two device variations for studied parameters.
CONCLUSIONS: Vasalgel's prevention of sperm transport for 14 months was reversed
through an intravasal injection of sodium bicarbonate. Post-reversal sperm
concentrations and motility returned to baseline levels during the six-month
follow up. Residual material in the vas lumen or compromised epididymal and vas
deferens function may be resulting in reduced forward progression and loss of
acrosomes during transit through the vas. Reduced forward progression and the
lack of normal acrosomes strongly suggest impaired sperm function.
PMID- 28417006
TI - First report of serotype 23B Streptococcus pneumoniae isolated from an adult
patient with invasive infection in Japan.
AB - Serotype 23B Streptococcus pneumoniae was isolated from a 67-year-old Japanese
patient with meningitis. This isolate was susceptible to penicillin G, while
genotyped as gPISP with a mutation in a penicillin-binding motif in PBP2b. The
23B isolate was assigned to ST11996 that is related to CC439, a dominant group
among serotype 23B.
PMID- 28417007
TI - Reappearance of buffalo-origin-like porcine circovirus type 2 strains in swine
herds in southern China.
AB - Previously, we identified three porcine circovirus type 2 (PCV2) strains in
buffalo meat samples from southern China. In this study, we confirmed the
reappearance of those buffalo-origin-like PCV2 strains in swine herds in this
region, which supported the possible cross-species infection of PCV2 between
buffalos and pigs under field conditions.
PMID- 28417008
TI - Association of gene coding variation and resting metabolic rate in a multi-ethnic
sample of children and adults.
AB - BACKGROUND: Resting metabolic rates (RMR) vary across individuals. Understanding
the determinants of RMR could provide biological insight into obesity and its
metabolic consequences such as type 2 diabetes and cardiovascular diseases.
METHODS: The present study measured RMR using reference standard indirect
calorimetry and evaluated genetic variations from an exome array in a sample of
children and adults (N = 262) predominantly of African and European ancestry with
a wide range of ages (10 - 67 years old) and body mass indices (BMI; 16.9 - 56.3
kg/m2 for adults, 15.1 - 40.6 kg/m2 for children). RESULTS: Single variant
analysis for RMR identified suggestive loci on chromosomes 15 (rs74010762, TRPM1,
p-value = 2.7 * 10-6), 1 (rs2358728 and rs2358729, SH3D21, p-values < 5.8x10-5),
17 (AX-82990792, DHX33, 5.5 * 10-5) and 5 (rs115795863 and rs35433829, C5orf33
and RANBP3L, p-values < 8.2 * 10-5). To evaluate the effect of low frequency
variations with RMR, we performed gene-based association tests. Our most
significant locus was SH3D21 (p-value 2.01 * 10-4), which also contained
suggestive results from single-variant analyses. A further investigation of all
variants within the reported genes for all obesity-related loci from the GWAS
catalog found nominal evidence for association of body mass index (BMI- kg/m2)
associated loci with RMR, with the most significant p-value at rs35433754 (TNKS,
p-value = 0.0017). CONCLUSIONS: These nominal associations were robust to
adjustment for BMI. The most significant variants were also evaluated using
phenome-wide association to evaluate pleiotropy, and genetically predicted gene
expression using the summary statistics implicated loci related to in obesity and
body composition. These results merit further examination in larger cohorts of
children and adults.
PMID- 28417009
TI - Revised definition of predicted left ventricular mass using ambulatory blood
pressure in healthy Korean adults.
AB - BACKGROUND: Left ventricular hypertrophy is influenced by both hemodynamic and
non-hemodynamic factors. Ambulatory blood pressure is correlated with left
ventricular hypertrophy. We established the influences of hemodynamic and non
hemodynamic factors, including ambulatory blood pressure, on variation in left
ventricular mass in healthy Korean adults. METHOD: We included 172 subjects (male
= 71, female = 101), with normal body mass index and blood pressure, in an
analysis of data from the Yangpyung and Yeoju cohort studies and a tertiary
cardiovascular center. Left ventricular mass was calculated using the equation:
[1.04 * (IVSd + LVDd + PWTd) 3-(LDVs3)] * 0.8 + 0.6. Stroke volume was calculated
(mL/beat) using Teichholz's formula. Stroke work (SW in gram-meters/beat [g
m/beat]) was computed as ambulatory systolic BP * stroke volume * 0.0144.
RESULTS: Stroke work was the most important determinant associated with left
ventricular mass (adjusted R2 = 0.442, p < 0.001), independent of height2.7 and
sex. In a regression model including stroke work, height,2.7 and sex, the left
ventricular mass was predicted by the equation: 43.11 + 0.61 * SW (g-m/beat) +
9.21 * height2.7-13.99 * sex (male = 1, female = 2) (constant = 43.11 +/- 25.88,
adjusted R2 = 0.532, p < 0.001). CONCLUSION: We examined ambulatory blood
pressure, as in previous studies, and identified stroke work, height2.7, and sex
as important determinants of left ventricular mass in Korean adults of normal
weight and normal blood pressure. Ambulatory blood pressure is superior to
clinical blood pressure for determining stroke work and predicted left
ventricular mass.
PMID- 28417010
TI - Astrocytes regulate the balance between plasminogen activation and plasmin
clearance via cell-surface actin.
AB - Plasminogen activation is involved in many processes within the central nervous
system, including synaptic plasticity, neuroinflammation and neurodegeneration.
However, the mechanisms that regulate plasminogen activation in the brain still
remain unknown. Here we demonstrate that astrocytes participate in this
regulation by two mechanisms. First, the astrocyte plasma membrane serves as a
surface for plasminogen activation by tissue-type plasminogen activator. This
activation triggers downstream plasmin-dependent processes with important impacts
in brain health and disease, such as fibrinolysis and brain-derived neurotrophic
factor conversion. Second, astrocytes take up plasminogen and plasmin in a
regulated manner through a novel mechanism involving endocytosis mediated by cell
surface actin and triggered by extracellular plasmin activity at the surface of
astrocytes. Following endocytosis, plasminogen and plasmin are targeted to
lysosomes for degradation. Thus, cell-surface actin acts as a sensor of plasmin
activity to induce a negative feedback through plasmin endocytosis. This study
provides evidence that astrocytes control the balance between plasmin formation
and plasmin elimination in the brain parenchyma.
PMID- 28417011
TI - Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling
by promoting TCF/beta-catenin transcriptional activity.
AB - Wnt/beta-catenin signaling regulates multiple biological processes and aberration
of this pathway is frequently observed in human cancers. Previously, we uncovered
NC043 as a small-molecule inhibitor of Wnt/beta-catenin signaling. Here, we
identified CARF as the cellular target of NC043. We found that NC043 binds
directly to CARF through forming a covalent bond with the Cys-516 residue of
CARF. Further study revealed that CARF interacts with Dvl, which potentiates the
Dvl-c-Jun-beta-catenin-TCF transcriptional complex and thus promotes Wnt
signaling activation. NC043 could disrupt the interaction between CARF and Dvl,
thereby impairing Wnt signal transduction. In line with this, knockdown of CARF
in zebrafish leads to impairment of embryonic development, hematopoietic stem
cell generation and caudal fin regeneration. Collectively, we identified CARF as
the cellular target of NC043 and revealed CARF as a positive regulator of
Wnt/beta-catenin signal transduction.
PMID- 28417013
TI - Erratum: Zika virus evades interferon-mediated antiviral response through the co
operation of multiple nonstructural proteins in vitro.
AB - [This corrects the article DOI: 10.1038/celldisc.2017.6.].
PMID- 28417014
TI - Ectogenic tension promotes fibrogenesis of mesenchymal stem cells through
microRNA-21.
PMID- 28417012
TI - Coordinating antigen cytosolic delivery and danger signaling to program potent
cross-priming by micelle-based nanovaccine.
AB - Although re-activating cytotoxic T-cell (CTLs) response inside tumor tissues by
checkpoint blockade has demonstrated great success in tumor immunotherapy, active
induction of efficient endogenous CTL response by therapeutic vaccines has been
largely hampered by inefficient cytosolic delivery of antigens and coordinated
activation of dendritic cells (DCs) in lymph nodes. Here we show that
polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles transform soluble
peptides into alpha-helix to enable their efficient cytosolic delivery. The same
PEG-PE micelles also serve as chaperon of TLR4 signaling to coordinate its
adjuvant effect on the same DCs. Furthermore, these nanovaccines effectively
target lymph node DCs. Thus, PEG-PE micelle vaccines program at multiple key
aspects for inducing strong CTL responses and build up a foundation for
combinational tumor therapy.
PMID- 28417015
TI - Characterization and isolation of highly purified porcine satellite cells.
AB - Pig is an important food source and an excellent system to model human diseases.
Careful characterization of the swine skeletal muscle stem cells (satellite
cells) will shed lights on generation of swine skeletal muscle disease model and
efficient production of porcine meat for the food industry. Paired box protein 7
(Pax7) is a highly conserved transcription factor shared by satellite cells from
various species. However, the sequence of Pax7 has not been characterized in pig.
The lack of method to isolate highly purified satellite cells hinders the
thorough characterization of the swine satellite cells. Here we found molecular
markers for swine satellite cells and revealed that the porcine satellite cells
were heterogeneous in various pieces of skeletal muscle. We further developed a
method to isolate highly purified satellite cells directly from porcine muscles
using fluorescence-activated cell sorting. We next characterized the
proliferation and differentiation abilities of isolated satellite cells in vitro;
and found that long-term culturing of satellite cells in vitro led to stemness
loss.
PMID- 28417016
TI - HMGB1 release by H2O2-induced hepatocytes is regulated through calcium overload
and 58-F interference.
AB - HMGB1 is passively released by injured or dying cells and aggravates inflammatory
processes. The release of HMGB1 and calcium overload have each been reported to
be important mediators of H2O2-induced injury. However, a potential connection
between these two processes remains to be elucidated. In the present study, we
employed H2O2-induced hepatocytes to investigate how calcium overload takes place
during cellular injury and how the extracellular release of HMGB1 is regulated by
this overload. In addition, we investigated the use of 58-F, a flavanone
extracted from Ophiopogon japonicus, as a potential therapeutic drug. We show
that the PLCgamma1-IP3R-SOC signalling pathway participates in the H2O2-induced
disturbance of calcium homoeostasis and leads to calcium overload in hepatocytes.
After a rise in intracellular calcium, two calcium-dependent enzymes, PKCalpha
and CaMKIV, are activated and translocated from the cytoplasm to the nucleus to
modify HMGB1 phosphorylation. In turn, this promotes HMGB1 translocation from the
nucleus to the cytoplasm and subsequent extracellular release. 58-F effectively
rescued the hepatocytes by suppressing the PLCgamma1-IP3R-SOC signalling pathway
and decreasing the calcium concentration in cells, thus reducing HMGB1 release.
PMID- 28417017
TI - Galectin-1 inhibition attenuates profibrotic signaling in hypoxia-induced
pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising
from epithelial injury, aberrant fibroblast growth, and excessive deposition of
extracellular matrix. Repeated epithelial injury elicits abnormal wound repair
and lung remodeling, often associated with alveolar collapse and edema, leading
to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult
that contributes to pulmonary fibrosis (PF) and define its molecular roles in
profibrotic activation of lung epithelial cells. Hypoxia increased transcription
of profibrotic genes and altered the proteomic signatures of lung epithelial
cells. Network analysis of the hypoxic epithelial proteome revealed a crosstalk
between transforming growth factor-beta1 and FAK1 (focal adhesion kinase-1)
signaling, which regulated transcription of galectin-1, a profibrotic molecule.
Galectin-1 physically interacted with and activated FAK1 in lung epithelial
cells. We developed a novel model of exacerbated PF wherein hypoxia, as a
secondary insult, caused PF in mice injured with subclinical levels of bleomycin.
Hypoxia elevated expression of phosphorylated FAK1, galectin-1, and alpha-smooth
muscle actin and reduced caspase-3 activation, suggesting aberrant injury repair.
Galectin-1 inhibition caused apoptosis in the lung parenchyma and reduced FAK1
activation, preventing the development of hypoxia-induced PF. Galectin-1
inhibition also attenuated fibrosis-associated lung function decline. Further,
galectin-1 transcript levels were increased in the lungs of IPF patients. In
summary, we have identified a profibrotic role of galectin-1 in hypoxia signaling
driving PF.
PMID- 28417019
TI - Heme oxygenase 1 governs the cytoskeleton at filopodia: pulling the brakes on the
migratory capacity of prostate tumoral cells.
PMID- 28417018
TI - DNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system
and inflammation.
AB - PP2C serine-threonine phosphatase, Wip1, is an important regulator of stress
response. Wip1 controls a number of critical cellular functions: proliferation,
cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy.
Ppm1d, the gene encoding Wip1 phosphatase, is expressed in hematopoietic
progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone
marrow and peripheral blood. The Wip1-/- mice display immunodeficiency, abnormal
lymphoid histopathology in thymus and spleen, defects in B- and T-cell
differentiation, as well as susceptibility to viral infection. At the same time,
Wip1 knockout mice exhibit pro-inflammatory phenotype in skin and intestine in
the model of inflammatory bowel disease (IBD) with elevated levels of
inflammation-promoting cytokines TNF-alpha, IL-6, IL-12, IL-17. Several Wip1
downstream targets can mediate Wip1 effects on hematopoietic system including,
p53, ATM, p38MAPK kinase, NFkB, mTOR. Here, we summarized the current knowledge
on the role of Wip1 in the differentiation of various hematopoietic lineages and
how Wip1 deficiency affects the functions of immune cells.
PMID- 28417020
TI - Anatomical Research: Misconceptions and opportunities.
PMID- 28417021
TI - Sentinel Lymph Node Biopsy: A new approach in the management of head and neck
cancers.
AB - Cervical lymph node metastasis affects the prognosis and overall survival rate of
and therapeutic planning for patients with head and neck squamous cell carcinomas
(HNSCCs). However, advanced diagnostic modalities still lack accuracy in
detecting occult neck metastasis. A sentinel lymph node biopsy is a minimally
invasive auxiliary method for assessing the presence of occult metastatic disease
in a patient with a clinically negative neck. This technique increases the
specificity of neck dissection and thus reduces morbidity among oral cancer
patients. The removal of sentinel nodes and dissection of the levels between the
primary tumour and the sentinel node or the irradiation of target nodal basins is
favoured as a selective treatment approach; this technique has the potential to
become the new standard of care for patients with HNSCCs. This article presents
an update on clinical applications and novel developments in this field.
PMID- 28417022
TI - Role of Travel Motivations, Perceived Risks and Travel Constraints on Destination
Image and Visit Intention in Medical Tourism: Theoretical model.
AB - Travel motivations, perceived risks and travel constraints, along with the
attributes and characteristics of medical tourism destinations, are important
issues in medical tourism. Although the importance of these factors is already
known, a comprehensive theoretical model of the decision-making process of
medical tourists has yet to be established, analysing the intricate relationships
between the different variables involved. This article examines a large body of
literature on both medical and conventional tourism in order to propose a
comprehensive theoretical framework of medical tourism decision-making. Many
facets of this complex phenomenon require further empirical investigation.
PMID- 28417023
TI - The Science of Anatomy: A historical timeline.
PMID- 28417024
TI - New Classification for Heart Failure with Mildly Reduced Ejection Fraction:
Greater clarity or more confusion?
AB - The latest European Society of Cardiology (ESC) guidelines for the diagnosis and
management of heart failure include a new patient group for those with heart
failure with mildly reduced ejection fraction (HFmrEF). By defining this group of
patients as a separate entity, the ESC hope to encourage more research focusing
on patients with HFmrEF. Previously, patients with this condition were caught
between two classifications-heart failure with reduced ejection fraction and
heart failure with preserved ejection fraction. Hopefully, the inclusion of new
terminology will not increase confusion, but rather aid our understanding of
heart failure, a complex clinical syndrome.
PMID- 28417025
TI - Dorsal Phalloplasty to Preserve Penis Length after Penile Prosthesis
Implantation.
AB - OBJECTIVES: Following penile prosthesis implantation (PPI), patients may complain
of a decrease in visible penis length. A dorsal phalloplasty defines the
penopubic junction by tacking pubic skin to the pubis, revealing the base of the
penis. This study aimed to evaluate the efficacy of a dorsal phalloplasty in
increasing the visible penis length following PPI. METHODS: An inflatable penile
prosthesis was implanted in 13 patients with severe erectile dysfunction (ED) at
the Kamal Shaeer Hospital, Cairo, Egypt, from January 2013 to May 2014. During
the surgery, nonabsorbable tacking sutures were used to pin the pubic skin to the
pubis through the same penoscrotal incision. Intraoperative penis length was
measured before and after the dorsal phalloplasty. Overall patient satisfaction
was measured on a 5-point rating scale and patients were requested to
subjectively compare their postoperative penis length with memories of their
penis length before the onset of ED. RESULTS: Intraoperatively, the dorsal
phalloplasty increased the visible length of the erect penis by an average of
25.6%. The average length before and after tacking was 10.2 +/- 2.9 cm and 13.7
+/- 2.8 cm, respectively (P <0.002). Postoperatively, seven patients (53.8%)
reported a longer penis, five patients (38.5%) reported no change in length and
one patient (7.7%) reported a slightly shorter penis. The mean overall patient
satisfaction score was 4.9 +/- 0.3. None of the patients developed postoperative
complications. CONCLUSION: A dorsal phalloplasty during PPI is an effective
method of increasing visible penis length, therefore minimising the impression of
a shorter penis after implantation.
PMID- 28417026
TI - Cardiovascular Complications of Acute Amphetamine Abuse: Cross-sectional study.
AB - OBJECTIVES: This study aimed to evaluate cardiovascular complications among
patients who abuse amphetamines. METHODS: This cross-sectional study took place
between April 2014 and April 2015 among 3,870 patients referred to the Toxicology
Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences,
Tehran, Iran. Those with clinical signs of drug abuse and positive urine
screening tests were included in the study, while cases of chronic abuse were
excluded. Cardiac complications were evaluated via electrocardiography (ECG) and
transthoracic echocardiography. RESULTS: A total of 230 patients (5.9%) had a
history of acute amphetamine abuse and positive urine tests. Of these, 32
patients (13.9%) were <20 years old and 196 (85.2%) were male. In total, 119
(51.7%) used amphetamine and methamphetamine compounds while 111 (48.3%) used
amphetamines with morphine or benzodiazepines. The most common ECG finding was
sinus tachycardia (43.0%), followed by sinus tachycardia plus a prolonged QT
interval (34.3%). Mean creatine kinase-MB and troponin I levels were 35.9 +/- 4.3
U/mL and 0.6 +/- 0.2 ng/mL, respectively. A total of 60 patients (26.1%) were
admitted to the Intensive Care Unit. The majority (83.3%) of these patients had
normal echocardiography results. The mean aortic root diameter (ARD) was 27.2 +/-
2.8 mm. Abnormalities related to the ARD were found in 10 patients (16.7%), three
of whom subsequently died. CONCLUSION: According to these findings, cardiac
complications were common among Iranian patients who abuse amphetamines, although
the majority of patients had normal echocardiography and ECG findings.
PMID- 28417027
TI - Decision-to-Delivery Time Intervals in Emergency Caesarean Section Cases:
Repeated cross-sectional study from Oman.
AB - OBJECTIVES: In cases of fetal intolerance to labour, meeting the standard
decision-to-delivery time interval (DDI) of <=30 minutes is challenging. This
study aimed to assess DDIs in emergency Caesarean section (CS) cases to identify
factors causing DDI delays and the impact of a delayed DDI on perinatal outcomes.
METHODS: This repeated cross-sectional study included all emergency CS procedures
performed due to acute fetal distress, antepartum haemorrhage or umbilical cord
prolapse at the Nizwa Hospital, Nizwa, Oman. Three audit cycles of three months
each were conducted between April 2011 and June 2013, including an initial
retrospective cycle and two prospective cycles following the implementation of
improvement strategies to address factors causing DDI delays. Poor perinatal
outcomes were defined as Apgar scores of <7 at five minutes, admission to the
Special Care Baby Unit (SCBU) or a stillbirth. RESULTS: In the initial cycle, a
DDI of <=30 minutes was achieved in 23.8% of 84 cases in comparison to 44.6% of
83 cases in the second cycle. In the third cycle, 60.8% of 79 women had a DDI of
<=30 minutes (P <0.001). No significant differences in perinatal outcomes for
cases with a DDI of <=30 minutes versus 31-60 minutes were observed; however, a
DDI of >60 minutes was significantly associated with poor neonatal outcomes in
terms of increased SCBU admissions and low Apgar scores (P <0.001 each). Factors
causing DDI delays included obtaining consent for the CS procedure, a lack of
operating theatre availability and moving patients to the operating theatre.
CONCLUSION: The identification of factors causing DDI delays may provide
opportunities to improve perinatal outcomes.
PMID- 28417028
TI - General Anaesthesia Protocols for Patients Undergoing Electroconvulsive Therapy:
Retrospective analysis of 504 sessions over a five-year period at a tertiary care
hospital in Oman.
AB - OBJECTIVES: This study aimed to review general anaesthesia protocols for patients
undergoing electroconvulsive therapy (ECT) at a tertiary care hospital in Oman,
particularly with regards to clinical profile, potential drug interactions and
patient outcomes. METHODS: This retrospective study took place at the Sultan
Qaboos University Hospital (SQUH), Muscat, Oman. The electronic medical records
of patients undergoing ECT at SQUH between January 2010 and December 2014 were
reviewed for demographic characteristics and therapy details. RESULTS: A total of
504 modified ECT sessions were performed on 57 patients during the study period.
All of the patients underwent a uniform general anaesthetic regimen consisting of
propofol and succinylcholine; however, they received different doses between
sessions, as determined by the treating anaesthesiologist. Variations in drug
doses between sessions in the same patient could not be attributed to any
particular factor. Self-limiting tachycardia and hypertension were periprocedural
complications noted among all patients. One patient developed aspiration
pneumonitis (1.8%). CONCLUSION: All patients undergoing ECT received a general
anaesthetic regimen including propofol and succinylcholine. However, the
interplay of anaesthetic drugs with ECT efficacy could not be established due to
a lack of comprehensive data, particularly with respect to seizure duration. In
addition, the impact of concurrent antipsychotic therapy on anaesthetic dose and
subsequent complications could not be determined.
PMID- 28417029
TI - Contraceptive Utilisation Among Mothers of Reproductive Age in Ajman, United Arab
Emirates.
AB - OBJECTIVES: This study aimed to determine contraceptive utilisation among mothers
aged 18-49 years old in Ajman, United Arab Emirates (UAE). METHODS: This cross
sectional study was carried out from May to November 2013. A total of 400
participants were recruited from two primary healthcare centres and one private
hospital in Ajman. An interviewer-administered validated questionnaire was used
for data collection. RESULTS: The frequency of previous and current contraceptive
use was 68.0% and 61.8%, respectively. Expatriates more frequently used
contraceptives in comparison to Emiratis (77.3% versus 54.3%, respectively).
Contraceptive use increased significantly with age (75.5% among >35-year-olds
versus 57.3% among <=25-year-olds; P <0.050) and education level (83.3% among
postgraduates versus 60.0% among those with primary education; P <0.050). In
addition, contraceptive use was significantly higher among those living in a
nuclear family system (P <0.050). A univariate analysis indicated significant
associations between contraceptive use and age, nationality, education level,
type of family system, employment sector, parity, knowledge of birth control
measures and source of birth control information (P <0.050 each). However, no
significant associations were found via multivariate analysis. CONCLUSION:
Healthcare practitioners can play a pivotal role in providing contraceptive
advice which could lead to an improvement in contraceptive utilisation. Efforts
are recommended to raise awareness regarding newer forms of contraceptives among
mothers of reproductive age in the UAE.
PMID- 28417030
TI - Knowledge and Attitudes Towards Basic Life Support Among Health Students at a
Saudi Women's University.
AB - OBJECTIVES: Awareness of basic life support (BLS) is paramount to ensure the
provision of essential life-saving medical care in emergency situations. This
study aimed to measure knowledge of BLS and attitudes towards BLS training among
female health students at a women's university in Saudi Arabia. METHODS: This
prospective cross-sectional study took place between January and April 2016 at
five health colleges of the Princess Nourah bint Abdulrahman University, Riyadh,
Saudi Arabia. All 2,955 students attending the health colleges were invited to
participate in the study. Participants were subsequently asked to complete a
validated English-language questionnaire which included 21 items assessing
knowledge of BLS and six items gauging attitudes to BLS. RESULTS: A total of
1,349 students completed the questionnaire (response rate: 45.7%). The mean
overall knowledge score was very low (32.7 +/- 13.9) and 87.9% of the
participants had very poor knowledge scores. A total of 32.5% of the participants
had never received any BLS training. Students who had previously received BLS
training had significantly higher knowledge scores (P <0.001), although their
knowledge scores remained poor. Overall, 77.0% indicated a desire to receive
additional BLS training and 78.5% supported mandatory BLS training. CONCLUSION:
Overall knowledge about BLS among the students was very poor; however, attitudes
towards BLS training were positive. These findings call for an improvement in BLS
education among Saudi female health students so as to ensure appropriate
responses in cardiac arrest or other emergency situations.
PMID- 28417031
TI - Knowledge, Practice and Self-Efficacy in Evidence-Based Practice among Midwives
in East Iran.
AB - OBJECTIVES: The successful implementation of evidence-based practice (EBP) can
lead to appropriate and effective midwifery care during pregnancy, childbirth and
in the postnatal period. However, levels of knowledge and confidence in one's
ability to apply EBP are related to its effective implementation. This study
aimed to investigate levels of knowledge, practice of and self-efficacy towards
the use of EBP among midwives in East Iran. METHODS: This cross-sectional study
took place between January and February 2016 and involved 98 midwives employed at
two hospitals and all four urban health care centres in Torbat-e Heydariyeh,
Iran. Two subscales of the Evidence-Based Practice Questionnaire were used to
assess participants' knowledge and practice of EBP, respectively, while a
modified version of a previously described scale was used to determine self
efficacy. RESULTS: A total of 76 midwives participated in the study (response
rate: 77.6%). Mean knowledge, practice and self-efficacy scores were 4.48 +/-
0.94, 3.53 +/- 0.68 and 2.80 +/- 0.81, respectively. Significant relationships
were found between mean self-efficacy, practice and knowledge scores and
proficiency in English language (P = 0.001 each) and statistical methods (P
<0.050 each). Additionally, significant relationships were found between
knowledge and practice of EBP and proficiency in the use of databases (P <0.050
each). Knowledge and self-efficacy scores were significantly correlated with
practice (P = 0.001 each). CONCLUSION: These findings demonstrate a need for
improvement in the self-efficacy, practice and knowledge of EBP among midwives in
East Iran. Interventions that promote these factors may help increase the use of
EBP in this population.
PMID- 28417032
TI - Vision Screening of Ophthalmic Nursing Staff in a Tertiary Eye Care Hospital:
Outcomes and ocular healthcare-seeking behaviours.
AB - OBJECTIVES: This study aimed to evaluate ocular healthcare-seeking behaviours and
vision screening outcomes of nursing staff at a tertiary eye care hospital.
METHODS: This study was conducted between April and September 2016 among all 500
nurses employed at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Data were collected on age, gender, use of visual aids, the presence of diabetes,
a history of refractive surgery and date of last ocular health check-up.
Participants were tested using a handheld SpotTM Vision Screener (Welch Allyn
Inc., Skaneateles Falls, New York, USA). RESULTS: A total of 150 nurses
participated in the study (response rate: 30.0%). The mean age was 41.2 +/- 8.9
years old. Distance spectacles, reading spectacles and both types of spectacles
were used by 37 (24.7%), 32 (21.3%) and 10 (6.7%) nurses, respectively. A total
of 58 nurses (38.7%) failed the vision screening test. Visual defects were
detected for the first time in 13 nurses (8.7%). With regards to regular eye
checkups, 77 participants (51.3%) reported acceptable ocular healthcare-seeking
behaviours; this factor was significantly associated with age and the use of
visual aids (P <0.01 each). CONCLUSION: A high proportion of participants failed
the vision screening tests and only half displayed good ocular healthcare-seeking
behaviours. This is concerning as ophthalmic nurses are likely to face fewer
barriers to eye care services than the general population.
PMID- 28417033
TI - Validation of a Persian Short-Form Version of a Standardised Questionnaire
Assessing Oral Cancer Knowledge, Practice and Attitudes Among Dentists.
AB - OBJECTIVES: Oral cancer is a global health problem; however, many dentists lack
the necessary skills, knowledge and capacity to diagnose oral cancers early. This
study aimed to examine the validity and reliability of a Persian short-form
version of a standardised questionnaire to assess dentists' knowledge, practice
and attitudes towards oral cancer. METHODS: This cross-sectional analytical study
was carried out in May 2015 in Tehran, Iran. An original 39-item English-language
questionnaire developed by Yellowitz et al. was translated into Persian using
forward and backward translation methods. A total of 15 dental professionals were
asked to assess the questionnaire for content validity. Based on their feedback,
a 20-item short-form version was prepared, including six demographic, six
knowledge, four attitude and four practice items. The translated short-form
questionnaire was subsequently distributed to 973 general dental practitioners
attending a dental conference in Tehran. Internal consistency and reliability
were assessed with Cronbach's alpha coefficient and item-total correlation
calculations. RESULTS: A total of 13 professionals and 313 general dentists
participated in the study (response rates: 86.7% and 32.2%, respectively). After
the elimination of six items (two knowledge, two attitude and two practice
items), the validity and reliability of the questionnaire was confirmed.
CONCLUSION: The final Persian 14-item version of the questionnaire had acceptable
validity and internal consistency. These results indicate that researchers can
use this translated short-form version to evaluate oral cancer knowledge,
attitudes and practices among Persian-speaking dentists; this will allow for a
comparison of data between different populations.
PMID- 28417034
TI - Knowledge Regarding Secondary Prevention Lifestyle Practices Among Patients with
Ischaemic Heart Disease in Oman: Pilot study.
AB - OBJECTIVES: Secondary prevention of ischaemic heart disease (IHD) is very
important. This study aimed to assess knowledge of necessary lifestyle changes
among Omani patients diagnosed with IHD. METHODS: This cross-sectional pilot
study took place between October 2015 and February 2016 at the Sultan Qaboos
University Hospital (SQUH), Muscat, Oman. A total of 30 random patients with IHD
from the Cardiology Outpatient Clinic of SQUH were included. A 30-item survey was
used to determine patients' knowledge of necessary lifestyle practices following
their IHD diagnosis, with scores of <70% indicating poor knowledge. RESULTS:
Overall, 21 patients (70.0%) had low knowledge levels. Scores ranged from 38.9
94.4% (mean: 60.7% +/- 14.1%). No demographic factors were found to predict low
scores, although there were some differences in individual questions. CONCLUSION:
Low knowledge levels regarding lifestyle changes were observed among IHD patients
in Oman. More efforts should be made to educate these patients for the secondary
prevention of IHD.
PMID- 28417035
TI - Jaw Osteomyelitis as a Complication of Sickle Cell Anaemia in Three Omani
Patients: Case reports and literature review.
AB - Sickle cell anaemia (SCA) is a common haemoglobinopathy among people from the
Middle East, the Afro-Caribbean region, the Mediterranean and East India. While
osteomyelitis of the long bones is a well-documented complication of SCA, there
are few documented cases of SCA patients presenting with jaw osteomyelitis. We
report three SCA patients with chronic jaw osteomyelitis who presented to the
Department of Oral Health, Sultan Qaboos University Hospital, Muscat, Oman,
between 2009 and 2013. Two of the patients had osteomyelitis of the mandible and
the third had osteomyelitis of the maxilla. In addition, a brief review of the
literature is presented focusing on the clinical presentation, diagnosis and
management of jaw osteomyelitis among patients with SCA.
PMID- 28417036
TI - Verrucous Hyperplasia: Case report and differential diagnosis.
AB - Verrucous hyperplasia (VH) is a rare exophytic oral mucosal lesion which can
transform into verrucous carcinoma (VC), its malignant but clinically similar
counterpart. These entities can be distinguished by the lack of invasive growth
in VH cases; as such, it is essential to include a margin with adequate depth
when performing a biopsy of the epithelium of the lesion. We report an 80-year
old male patient who presented to the Bapuji Dental College & Hospital,
Davangere, Karanataka, India, in 2011 with a warty whitish-pink growth on the
inside of his cheek. The patient was treated with wide surgical excision of the
lesion and a diagnosis of VH was made based on histopathological features. There
was no evidence of recurrence at a five-year follow-up. This report highlights
the histological variations, pathogenesis and differential diagnosis of VH.
PMID- 28417037
TI - Additional Muscle Slip of Bicipital Aponeurosis and its Anomalous Relationship
with the Median Cubital Vein.
AB - The cubital region of the arm is a common site for recording blood pressure,
taking blood for analysis and administering intravenous therapy and blood
transfusions. During the routine dissection of a 70-year-old male cadaver at the
Kasturba Medical College, Manipal, Karnataka, India, in 2015, it was observed
that the aponeurotic insertion of the biceps brachii muscle divided into two
slips. The medial slip fused normally with the deep fascia of the forearm, while
flexor carpi radialis muscle fibres originated from the lateral slip. There was
also a single vein in the forearm, the cephalic vein, which bifurcated to form
the median cubital vein and the cephalic vein proper. The median cubital vein,
further reinforced by the radial vein, passed deep to the two slips of the
bicipital aponeurosis and then continued as the basilic vein. During
venepuncture, medical practitioners should be aware of potential cubital fossa
variations which could lead to nerve entrapment syndromes.
PMID- 28417038
TI - Anomalous Innervation of the Median Nerve in the Arm in the Absence of the
Musculocutaneous Nerve.
AB - The brachial plexus innervates the upper extremities. While variations in the
formation of the brachial plexus and its terminal branches are quite common, it
is uncommon for the median nerve to innervate the muscles of the arm. During the
dissection of an elderly male cadaver at the Department of Anatomy, All India
Institute of Medical Sciences, New Delhi, India, in 2016, the coracobrachialis
muscle was found to be supplied by a direct branch from the lateral root of the
median nerve and the musculocutaneous nerve was absent. The branches of the
median nerve supplied the biceps brachii and brachialis muscles and the last
branch continued as the lateral cutaneous nerve of the forearm. These variations
may present atypically in cases of arm flexor paralysis or sensory loss on the
lateral forearm. Knowledge of these variations is important in surgeries and
during the administration of regional anaesthesia near the shoulder joint and
upper arm.
PMID- 28417039
TI - A True Human Tail in a Neonate: Case report and literature review.
AB - A true human tail is a benign vestigial caudal cutaneous structure composed of
adipose, connective tissue, muscle, vessels, nerves and mechanoreceptors. A true
human tail can be distinguished from a pseudotail as the latter is commonly
associated with underlying spinal dysraphism, which requires specialised
management. True human tails are very rare, with fewer than 40 cases reported to
date. We report a healthy one-day-old male newborn who was referred to the
Bharath Hospital, Kottayam, Kerala, India, in 2014 with a cutaneous appendage
arising from the lumbosacral region. Magnetic resonance imaging of the spine
ruled out spinal dysraphism. The appendage was removed by simple surgical
excision. Clinicians should emphasise use of 'true tail' and 'pseudotail' as
specific disparate terms as the clinical, radiological and histological findings
of these conditions differ significantly, along with management strategies and
outcomes.
PMID- 28417040
TI - Unusual Branching Pattern of the Lateral Cord of the Brachial Plexus Associated
with Neurovascular Compression: Case report.
AB - The brachial plexus consists of a network of nerves that innervates the upper
limbs and its musculature. We report a rare formation of the lateral cord of the
brachial plexus observed during the dissection of a 47-year-old male cadaver at
the Department of Anatomy, Vardhman Mahavir Medical College, New Delhi, India, in
2016. The lateral cord was exceptionally long with twin lateral pectoral nerves
and twin lateral roots of the median nerve. The proximal lateral root of the
median nerve was thin in comparison to the medial root of the median nerve. The
distal lateral root of the median nerve was thicker and followed an unusual
course through the coracobrachialis muscle. In the lower third of the arm, the
median nerve and the brachial artery-along with its vena comitans-spanned through
the brachialis muscle. Surgeons, anaesthesiologists, radiologists and anatomists
should be aware of such anatomical variations as they may result in neurovascular
compression.
PMID- 28417042
TI - Accessory Duct of the Submandibular Gland.
PMID- 28417041
TI - Focal Scalp Hair Heterochromia in an Infant.
AB - Hair heterochromia involves the presence of two different non-artificially
induced colours of hair in the same individual which can be due to either iron
deficiency anaemia, genetic mutations or mosaicism. We report a six-month old
male infant who presented to the Department of Dermatology, Saham Hospital,
Saham, Oman, in 2013 with focal scalp hair heterochromia without any detectable
underlying abnormalities. The area of heterochromia was still noticeable at a one
year follow-up.
PMID- 28417043
TI - Extensive Fixed Drug Eruption Due to Diclofenac.
PMID- 28417044
TI - MEDLINE(r) Indexing of the Sultan Qaboos University Medical Journal: A great leap
forward for biomedical research and publishing in the Gulf region.
PMID- 28417045
TI - A Turning Point for Paediatric Developmental Services in Oman: Establishment of a
national autism screening programme.
PMID- 28417046
TI - Re: Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous
Sclerosis Complex: Case reports and review of literature.
PMID- 28417047
TI - Clinical significance of SNP (rs2596542) in histocompatibility complex class I
related gene A promoter region among hepatitis C virus related hepatocellular
carcinoma cases.
AB - The major histocompatibility complex class I-related gene A (MICA) is an antigen
induced by stress and performs an integral role in immune responses as an anti
infectious and antitumor agent. This work was designed to investigate whether
(SNP) rs2596542C/T in MICA promoter region is predictive of liver cirrhosis (LC)
and hepatocellular carcinoma (HCC) or not. Forty-seven healthy controls and 94
HCV-infected patients, subdivided into 47 LC and 47 HCC subjects were enrolled in
this study. SNP association was studied using real time PCR and soluble serum
MICA concentration was measured using ELISA. Results showed that heterozygous
genotype rs2596542CT was significantly (P = 0.022) distributed between HCC and LC
related CHC patients. The sMICA was significantly higher (P = 0.0001) among HCC
and LC. No significant association (P = 0.56) between rs2596542CT genotypes and
sMICA levels was observed. Studying SNP rs2596542C/T association with HCC and LC
susceptibility revealed that statistical significant differences (P = 0.013, P =
0.027) were only observed between SNP rs2596542C/T and each of HCC and LC,
respectively, versus healthy controls, indicating that the rs2596542C/T genetic
variation is not a significant contributor to HCC development in LC patients.
Moreover, the T allele was considered a risk factor for HCC and LC vulnerability
in HCV patients (OR = 1.93 and 2.1, respectively), while the C allele contributes
to decreasing HCC risk. Therefore, SNP (rs2596542C/T) in MICA promoter region and
sMICA levels might be potential useful markers in the assessment of liver disease
progression to LC and HCC.
PMID- 28417048
TI - Is tricuspid valve really tricuspid?
AB - Advancement in imaging techniques and interventional cardiology procedures have
generated renewed interest in anatomy of tricuspid valve complex. The purpose of
the present study was to characterize the morphology of tricuspid valve leaflets
using objective criteria. Thirty-six embalmed cadaveric hearts were utilized for
the present study. Leaflet morphology was studied using newly defined criteria.
Commissural zones were identified and leaflets were delineated. Presence of
scallops was also recorded. Single leaflet was observed in six cases, double in
26 cases, and triple in four cases. The anterior leaflet is large with multiple
scallops and frequently accrues portion of inferior leaflet. The septal leaflet
is in the form of a plateau and also frequently accrues parts of inferior
leaflet. The inferior leaflet rarely occurs as independent leaflet. A wide un
indented basal zone exists across the valve leaflets. The study found that the
tricuspid valve is rarely tricuspid. It also generated the hypotheses that the
tricuspid valve does not open completely due to presence of a wide basal zone and
the valve does not close completely owing to incongruence and lack of coaptation
of leaflets. The findings provide clear understanding of leaflet morphology of
tricuspid valve. This will help imaging specialists for interpretation of images
and cardiologists for interventional procedures. The findings also enhance our
understanding of pathophysiology of conditions like functional tricuspid
regurgitation.
PMID- 28417049
TI - Morphometric study of tensor of vastus intermedius in South Indian population.
AB - Tensor of vastus intermedius is a newly discovered muscle located between vastus
lateralis and vastus intermedius. The purpose of this study was to investigate
the detailed morphology of tensor of vastus intermedius, specifically to provide
data pertaining to the attachments, innervations, variation in the types and its
morphometry in South Indian population. The tensor of vastus intermedius was
studied in thirty six cadaveric lower limbs using macrodissection techniques. The
origin of the muscle was from upper part of intertrochanteric line and anterior
part of greater trochanter of femur inserted to medial aspect of upper border of
patella. The muscle was classified into four types based on the origin and also
the aponeurosis course with independent type (type 1) being common. The mean and
standard deviation of the length of tensor of vastus intermedius and aponeurosis
were 145.40+/-37.55 mm and 193.55+/-42.32 mm, respectively. The results of the
study suggest that tensor of vastus intermedius is variable and the information
provided regarding the attachments, types and quantitative data will contribute
to the existing knowledge of the muscle.
PMID- 28417050
TI - Venezuelan surgeons view concerning teaching human anatomical dissection.
AB - Currently, the importance of human anatomical dissection have come under debate
in many countries but there are not references in Venezuela on this concern. This
survey's aim is to assess the insights of Venezuelan surgeons and their outlines
of usage of human anatomical dissection in teaching and learning human anatomy.
Sixty-five Venezuelan surgeons at the Centro Medico Docente La Trinidad completed
an anonymous survey on current and future teaching practices in human anatomy.
Eighty-nine point two three percent of surveyed (n=58) conferred importance to
human anatomical dissection despite the arrival of new innovations in learning
human anatomy. The group surveyed view human anatomical dissection-based teaching
as the most beneficial method of teaching human anatomy and it should be
bolstered in human anatomical education with matching use of three-dimensional
computerized tomography imaging as a complementary form for teaching and
learning.
PMID- 28417051
TI - Morphology of cat vomeronasal organ non-sensory epithelium during postnatal
development.
AB - The vomeronasal organ has an important role in mammal's social and sexual
behaviours. In addition, it mediates defensive behavior through detection of
protein pheromone homologues. In this work, a detailed morphological description
of the postnatal development of the non-sensory epithelium (NSE) lining the
vomeronasal duct (VND) of the female cat is provided using various histological
techniques. The study focused on newborn, 2 weeks, 4 weeks, and 8 weeks of
postnatal ages using four animals for each age. We report here for the first time
that three types of NSE line the rostral segment of the VND; nonkeratinized
stratified squamous epithelium, stratified cuboidal epithelium, and ciliated
pseudo stratified columnar ciliated epithelium with goblet cells and that the VND
undergoes 90 degrees a change in its its axis from the vertical position
caudally to the horizontal position rostral. The NSE which lines the lateral side
of the VND middle segment is consists of cliated pseudostratified columnar
epithelium without goblet cells. In addition to basal cells, the NSE contains
ciliated and three types of nonciliated columnar epithelial cells (dark, light,
and unstained). Mitotic figures were observed only in the basal cells layer
during the first 2 weeks of postnatal development. Intraepithelial invading
inflammatory cells were uncommon. Scanning electron microscopy revealed unevenly
distributed long cilia intermingled with microvillar processes and intervening
short microvillar processes. These projecting cilia and microvilli revealed a
gradual increase in their height during development toward maturity.
PMID- 28417052
TI - Relationship between meiotic spindles visualization and intracytoplasmic sperm
injection outcomes in human oocytes.
AB - In assisted reproductive techniques, the operator attempts to select
morphologically best embryos to predict embryo viability. Development of
polarized light microscope, which evaluates the oocytes' spindles according to
birefringence of living cells, had been helpful in oocyte selection. The aim of
this study is evaluating the relationship between meiotic spindles visualization
and intracytoplasmic sperm injection (ICSI) outcomes in human oocytes. In this
study, 264 oocytes from 24 patients with an average age of 30.5+/-7.5 years with
infertility duration of 1 to 10 years were collected. The oocytes were randomly
allocated to the control injection group (n=126) and the oocyte imaging group
(spindle-aligned group) (n=138). In the spindle-aligned group, the meiotic
spindle was identified by means of polarized light microscope to align the
spindle at 6 or 12 o'clock. Then the spindle-aligned group was divided into three
sub-groups based on spindle morphology: fine, average, and (poor). After ICSI,
embryos were checked every 24 hours and scored; 72 hours later, high-grade
embryos were transferred intravaginally to uterus. This study showed that the
fertilization rate in the spindle-aligned group was higher than the control group
(P<0.05). After cleavage, a positive correlation was observed between spindle
morphology and embryo morphology. Among the sub-groups of spindle-aligned group,
the embryos' morphology of the fine group was better than the other subgroups and
embryos of the poor group had lower quality and more fragmentation. The results
revealed that the selection of oocytes based on meiotic spindle imaging can
significantly improve the rate of fertilization and embryo cleavage and certainly
increase the rate of implantation.
PMID- 28417053
TI - Pacinian corpuscle-like structure in the digital tendon sheath and nail bed: a
study using late-stage human fetuses.
AB - Pacinian corpuscle-like structures were identified in the digital tendon sheaths
and nail beds of hands obtained from eight of 12 human fetuses of gestational age
20-34 weeks (crown-rump length, 150-290 mm). The aberrant corpuscles were present
in tight fibrous tissue connecting the flexor tendon sheath to the dorsal
aponeurosis (138 corpuscles in the thumbs and all fingers of eight fetuses);
loose fibrous tissue inside the sheath on the dorsal side of the tendon (37
corpuscles in the thumbs and all fingers of four fetuses); and the nail bed (10
clusters in the thumbs and second fingers of four smaller fetuses). The aberrant
corpuscles in the tendon sheath were classified into two types: thin and short,
with tightly packed lamellae, of diameter 20-40 um and length 20-200 um; and
thick and long, with loosely packed lamellae, of diameter 70-150 um and length
0.5-1.5 mm. The small corpuscles tended to form clusters, each containing 5-10
structures. Their similarity indicated that the tight and loose lamellae in these
two types of corpuscles corresponded to typical immature and mature corpuscles,
respectively, usually distributed along the palmar digital nerve. However,
mature, large corpuscles were absent from the nail bed, and most aberrant
corpuscles were smaller than typical corpuscles along the nerve. The aberrant
corpuscles were apparently incorporated into the tendon sheath or nail bed during
fetal vascular development, but they appeared to degenerate after birth due to
mechanical stress from the tendon or nail.
PMID- 28417054
TI - Three-dimensional and topographic relationships between the orbital margins with
reference to assessment of eyeball protrusion.
AB - This study investigated the topographic relationships among the eyeball and four
orbital margins with the aim of identifying the correlation between orbital
geometry and eyeball protrusion in Koreans. Three-dimensional (3D) volume
rendering of the face was performed using serial computed-tomography images of
141 Koreans, and several landmarks on the bony orbit and the cornea were directly
marked on the 3D volumes. The anterior-posterior distances from the apex of the
cornea to each orbital margin and between the orbital margins were measured in
both eyes. The distances from the apex of the cornea to the superior, medial,
inferior, and lateral orbital margins were 5.8, 5.8, 12.0, and 17.9 mm,
respectively. Differences between sides were observed in all of the orbital
margins, and the distances from the apex of the cornea to the superior and
inferior orbital margins were significantly greater in females than in males. The
anterior-posterior distance between the superior and inferior orbital margins did
not differ significantly between males (6.3 mm) and females (6.2 mm). The data
obtained in this study will be useful when developing practical guidelines
applicable to forensic facial reconstruction and orbitofacial surgeries.
PMID- 28417055
TI - Potential involvement of glycogen synthase kinase (GSK)-3beta in a rat model of
multiple sclerosis: evidenced by lithium treatment.
AB - Glycogen synthase kinase (GSK)-3beta has been known as a pro-inflammatory
molecule in neuroinflammation. The involvement of GSK-3beta remains unsolved in
acute monophasic rat experimental autoimmune encephalomyelitis (EAE). The aim of
this study was to evaluate a potential role of GSK-3beta in central nervous
system (CNS) autoimmunity through its inhibition by lithium. Lithium treatment
significantly delayed the onset of EAE paralysis and ameliorated its severity.
Lithium treatment reduced the serum level of pro-inflammatory tumor necrosis
factor a but not that of interleukin 10. Western blot analysis showed that the
phosphorylation of GSK-3beta (p-GSK-3beta) and its upstream factor Akt was
significantly increased in the lithium-treated group. Immunohistochemical
examination revealed that lithium treatment also suppressed the activation of
ionized calcium binding protein-1-positive microglial cells and vascular cell
adhesion molecule-1 expression in the spinal cords of lithium-treated EAE rats.
These results demonstrate that lithium ameliorates clinical symptom of acute
monophasic rat EAE, and GSK-3 is a target for the suppression of acute
neuroinflammation as far as rat model of human CNS disease is involved.
PMID- 28417056
TI - Therapeutic effect of prostaglandin E1 in monocrotaline-induced pulmonary
arterial hypertension rats.
AB - Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease
characterized by sustained increase in pulmonary arterial pressure and excessive
thickening and remodeling of distal small pulmonary arteries. During disease
progression, PAH include increase in mean pulmonary arterial pressure, right
ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth
muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting
various pathways involved in PAH progression have been approved by the Food and
Drug Adminstration. However, many of the currently available anti-PAH drugs
suffer from a number of limitations, including short biological half-life, and
poor pulmonary selectivity. Prostaglandin E1 (PGE1) is a potent vasodilator with
selectivity toward pulmonary circulation when it is administered via the
pulmonary route. However, PGE1 has a very short half-life of 5-10 minutes.
Therefore, we hypothesized that long-term effect of PGE1 could reduce mal
adaptive structural remodeling of the lung and heart and prevent ventricular
arrhythmias in monocrotaline-induced rat model of PAH. Our results revealed that
PGE1 reduced ventricular hypertrophy, protein expressions of endothelin-1 and
endothelin receptor A, and the expression of fibrosis. These results support the
notion that PGE1 can improve the functional properties of RV, highlighting its
potential benefits for heart and lung impairment.
PMID- 28417057
TI - Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as
a potential of tumor marker.
AB - Prostate cancer is the most common cancer type in men and is the second cause of
death, due to cancer, in patients over 50, after lung cancer. Prostate specific
antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is
discovered in non-prostatic cancer tissues in men and women raising doubts about
its specificity for prostatic tissues. PSA exists in low serum level in healthy
men and in higher levels in many prostate disorders, including prostatitis and
prostate cancer. Thus, a supplementary tumor marker is needed to accurately
diagnose the cancer and to observe the patient after treatment. Recently, soluble
human leukocyte antigen-G (sHLA-G) has been introduced as a new tumor marker for
different cancer types, including colorectal, breast, lung, and ovary. The
present descriptive-experimental study was carried out including patients with
malignant prostate tumor, patients with benign prostate tumor, and a group of
health men as the control group, as judged by an oncologist as well as a
pathologist. After sterile blood sampling, sHLA-G was measured by enzyme-linked
immunosorbent assay in each group. The data was then analyzed using one-way
ANOVA. P<=0.05 was considered as statistically significant. The results showed
that the mean of sHLA-G level was high in patients. Also, it was found that there
was a significant difference in sHLA serum level between the three groups. The
data revealed that sHLA-G can be a novel supplementary tumor marker in addition
to PSA to diagnose prostate cancer.
PMID- 28417058
TI - Recognition of a rare intrathoracic rib with computed tomography: a case report.
AB - One of the uncommon congenital variations is intrathoracic rib which a normal, a
bifid, or an accessory rib lies within the thoracic cavity that is founded
accidentally. Clinically, in most cases they are without symptoms; however, it
may cause intrathoracic problems therefore it is important for radiologists and
physicians to identify to prevent of excessive intervention and treatment during
imaging diagnostic techniques of thoracic problems. In this report, we provide
the case of a rare presentation of an intrathoracic rib in a 3-year-old boy
arising from the inferior portion of a second rib based on findings from computed
tomography. To our knowledge, this is only the second reported case of this type
of intrathoracic rib that demonstrated with computed tomography.
PMID- 28417059
TI - Susceptibility of Human Oral Squamous Cell Carcinoma (OSCC) H103 and H376 cell
lines to Retroviral OSKM mediated reprogramming.
AB - Although numbers of cancer cell lines have been shown to be successfully
reprogrammed into induced pluripotent stem cells (iPSCs), reprogramming Oral
Squamous Cell Carcinoma (OSCC) to pluripotency in relation to its cancer cell
type and the expression pattern of pluripotent genes under later passage remain
unexplored. In our study, we reprogrammed and characterised H103 and H376 oral
squamous carcinoma cells using retroviral OSKM mediated method. Reprogrammed
cells were characterized for their embryonic stem cells (ESCs) like morphology,
pluripotent gene expression via quantitative real-time polymerase chain reaction
(RT-qPCR), immunofluorescence staining, embryoid bodies (EB) formation and
directed differentiation capacity. Reprogrammed H103 (Rep-H103) exhibited similar
ESCs morphologies with flatten cells and clear borders on feeder layer.
Reprogrammed H376 (Rep-H376) did not show ESCs morphologies but grow with a
disorganized morphology. Critical pluripotency genes Oct4, Sox2 and Nanog were
expressed higher in Rep-H103 against the parental counterpart from passage 5 to
passage 10. As for Rep-H376, Nanog expression against its parental counterpart
showed a significant decrease at passage 5 and although increased in passage 10,
the level of expression was similar to the parental cells. Rep-H103 exhibited
pluripotent signals (Oct4, Sox2, Nanog and Tra-1-60) and could form EB with the
presence of three germ layers markers. Rep-H103 displayed differentiation
capacity into adipocytes and osteocytes. The OSCC cell line H103 which was able
to be reprogrammed into an iPSC like state showed high expression of Oct4, Sox2
and Nanog at late passage and may provide a potential iPSC model to study multi
stage oncogenesis in OSCC.
PMID- 28417060
TI - Burden and predictors of Staphylococcus aureus and S. pseudintermedius infections
among dogs presented at an academic veterinary hospital in South Africa (2007
2012).
AB - BACKGROUND: Staphylococci are commensals of the mucosal surface and skin of
humans and animals, but have been implicated in infections such as otitis
externa, pyoderma, urinary tract infections and post-surgical complications.
Laboratory records provide useful information to help investigate these
infections. Therefore, the objective of this study was to investigate the burdens
of these infections and use multinomial regression to examine the associations
between various Staphylococcus infections and demographic and temporal factors
among dogs admitted to an academic veterinary hospital in South Africa. METHODS:
Records of 1,497 clinical canine samples submitted to the bacteriology laboratory
at a veterinary academic hospital between 2007 and 2012 were included in this
study. Proportions of staphylococcal positive samples were calculated, and a
multinomial logistic regression model was used to identify predictors of
staphylococcal infections. RESULTS: Twenty-seven percent of the samples tested
positive for Staphylococcus spp. The species of Staphylococcus identified were S.
pseudintermedius (19.0%), S. aureus (3.8%), S. epidermidis (0.7%) and S. felis
(0.1%). The remaining 2.87% consisted of unspeciated Staphylococcus. Distribution
of the species by age of dog showed that S. pseudintermedius was the most common
(25.6%) in dogs aged 2-4 years while S. aureus was most frequent (6.3%) in dogs
aged 5-6 years. S. pseudintermedius (34.1%) and S. aureus (35.1%) were the most
frequently isolated species from skin samples. The results of the multivariable
multinomial logistic regression model identified specimen, year and age of the
dog as significant predictors of the risk of infection with Staphylococcus. There
was a significant temporal increase (RRR = 1.17; 95% CI [1.06-1.29]) in the
likelihood of a dog testing positive for S. pseudintermedius compared to testing
negative. Dogs <= 8 years of age were significantly more likely to test positive
for S. aureus than those >8 years of age. Similarly, dogs between 2-8 years of
age were significantly more likely to test positive for S. pseudintermedius than
those >8 years of age. In addition, dogs 2-4 years of age (RRR = 1.83; 1.09-3.06)
were significantly more likely to test positive for S. pseudintermedius compared
to those <2 years of age. The risk of infection with S. pseudintermedius or S.
aureus was significantly higher in ear canal and skin specimens compared to other
specimens. CONCLUSIONS: The findings suggest that S. pseudintermedius and S.
aureus were the most commonly isolated species from dogs presented at the study
hospital. Age of the dog and the location of infection were significant
predictors of infection with both Staphylococcus species investigated.
Significant increasing temporal trend was observed for S. pseudintermedius but
not S. aureus. This information is useful for guiding clinical decisions as well
as future research.
PMID- 28417061
TI - Rates of morphological evolution in Captorhinidae: an adaptive radiation of
Permian herbivores.
AB - The evolution of herbivory in early tetrapods was crucial in the establishment of
terrestrial ecosystems, although it is so far unclear what effect this innovation
had on the macro-evolutionary patterns observed within this clade. The clades
that entered this under-filled region of ecospace might be expected to have
experienced an "adaptive radiation": an increase in rates of morphological
evolution and speciation driven by the evolution of a key innovation. However
such inferences are often circumstantial, being based on the coincidence of a
rate shift with the origin of an evolutionary novelty. The conclusion of an
adaptive radiation may be made more robust by examining the pattern of the
evolutionary shift; if the evolutionary innovation coincides not only with a
shift in rates of morphological evolution, but specifically in the morphological
characteristics relevant to the ecological shift of interest, then one may more
plausibly infer a causal relationship between the two. Here I examine the impact
of diet evolution on rates of morphological change in one of the earliest
tetrapod clades to evolve high-fibre herbivory: Captorhinidae. Using a method of
calculating heterogeneity in rates of discrete character change across a
phylogeny, it is shown that a significant increase in rates of evolution
coincides with the transition to herbivory in captorhinids. The herbivorous
captorhinids also exhibit greater morphological disparity than their faunivorous
relatives, indicating more rapid exploration of new regions of morphospace. As
well as an increase in rates of evolution, there is a shift in the regions of the
skeleton undergoing the most change; the character changes in the herbivorous
lineages are concentrated in the mandible and dentition. The fact that the
increase in rates of evolution coincides with increased change in characters
relating to food acquisition provides stronger evidence for a causal relationship
between the herbivorous diet and the radiation event.
PMID- 28417062
TI - Community partnerships in healthy eating and lifestyle promotion: A network
analysis.
AB - Promoting healthy eating and lifestyles among populations with limited resources
is a complex undertaking that often requires strong partnerships between various
agencies. In local communities, these agencies are typically located in different
areas, serve diverse subgroups, and operate distinct programs, limiting their
communication and interactions with each other. This study assessed the network
of agencies in local communities that promote healthy eating and lifestyles among
populations with limited resources. Network surveys were administered in 2016
among 89 agencies located in 4 rural counties in Michigan that served limited
resource audiences. The agencies were categorized into 8 types: K-12 schools,
early childhood centers, emergency food providers, health-related agencies,
social resource centers, low-income/subsidized housing complexes, continuing
education organizations, and others. Network analysis was conducted to examine 4
network structures-communication, funding, cooperation, and collaboration
networks between agencies within each county. Agencies had a moderate level of
cooperation, but were only loosely connected in the other 3 networks, indicated
by low network density. Agencies in a network were decentralized rather than
centralized around a few influential agencies, indicated by low centralization.
There was evidence regarding homophily in a network, indicated by some
significant correlations within agencies of the same type. Agencies connected in
any one network were considerably more likely to be connected in all the other
networks as well. In conclusion, promoting healthy eating and lifestyles among
populations with limited resources warrants strong partnership between agencies
in communities. Network analysis serves as a useful tool to evaluate community
partnerships and facilitate coalition building.
PMID- 28417063
TI - Melanized fungus as an Epidural abscess: A diagnostic and therapeutic challenge.
AB - Curvularia a dematiaceous fungus is ubiquitously found in soil around the world.
We report an epidural abscess due to Curvularia lunata in a 48 years male farmer
who underwent decompressive laminectomy as primary modality of treatment followed
by isolation, identification and confirmation of the isolate from tissue by ITS
sequencing. Antifungal therapy with voriconazole and amphotericin B for 3 and 2
weeks respectively improved patient's condition and is presently on regular
follow up with no sequelae since last 7 months.
PMID- 28417064
TI - Adenocarcinoma of the lung presenting as thrombotic thrombocytopenic purpura.
AB - Acquired thrombotic thrombocytopenic purpura (TTP) usually presents as severe
microangiopathic hemolytic anemia (MAHA) and thrombocytopenia in a previously
healthy individual. It occurs in approximately three in one million adults and 1
in 10 million children annually. The incidence is increased in females and
blacks. Diagnosing TTP and initiating therapy with plasma exchange is a must to
avoid preventable complications. Acquired thromotic microangiopathy has been
linked to collagen vascular diseases, use of certain medications, organ
transplants, infections, pregnancy and cancer. We report a rare case of a 56-year
old African American male diagnosed with TTP who found to have an asymptomatic
adenocarcinoma of the lung. Prompt cancer management resulted in completed
remission of the thrombotic microangiopathy.
PMID- 28417065
TI - Progressive dyspnea due to pulmonary carcinoid tumorlets.
AB - This is a case description of a female patient, 77 years-old, who presented with
progressive dyspnea and cough. She had a mild hypoxemia in the arterial blood
gases (PaO2 72 mmHg) and normal spirometry. The chest computer tomography
revealed diffuse "ground glass" opacities, segmental alveolitis, bronchiectasis,
fibrotic lesions and numerous micronodules. A thoracoscopy was performed and the
obtained biopsy showed carcinoid tumorlets, with positive CK8/18, CD56, TTF-1 and
synaptophysin immunohistochemical markers. Pulmonary carcinoid tumorlets are
rare, benign lesions and individuals with tumorlets are typically asymptomatic.
Our report presents a symptomatic clinical case of carcinoid tumorlet.
PMID- 28417066
TI - Ezogabine skin discoloration is reversible after discontinuation.
AB - There is concern that bluish skin discoloration associated with ezogabine
treatment could be permanent. We present a case of ezogabine-induced skin
discoloration that resolved completely after discontinuation. A 55-year-old woman
started ezogabine 400 mg three times a day at age 41. Bluish pigmentation over
the toe nails, finger nails, around eyes and over and around lips was first noted
after 5 years of treatment. Ezogabine was discontinued eight years after
initiation. Skin discoloration improved within 6 months and completely resolved
within 6 years of discontinuation. This case suggests that ezogabine-induced
discoloration is reversible after discontinuation of treatment.
PMID- 28417067
TI - Quantitative photoacoustic integrating sphere (QPAIS) platform for absorption
coefficient and Gruneisen parameter measurements: Demonstration with human blood.
AB - Quantitative photoacoustic imaging in biomedicine relies on accurate measurements
of relevant material properties of target absorbers. Here, we present a method
for simultaneous measurements of the absorption coefficient and Gruneisen
parameter of small volume of liquid scattering and absorbing media using a
coupled-integrating sphere system which we refer to as quantitative photoacoustic
integrating sphere (QPAIS) platform. The derived equations do not require
absolute magnitudes of optical energy and pressure values, only calibration of
the setup using aqueous ink dilutions is necessary. As a demonstration,
measurements with blood samples from various human donors are done at room and
body temperatures using an incubator. Measured absorption coefficient values are
consistent with known oxygen saturation dependence of blood absorption at 750 nm,
whereas measured Gruneisen parameter values indicate variability among five
different donors. An increasing Gruneisen parameter value with both hematocrit
and temperature is observed. These observations are consistent with those
reported in literature.
PMID- 28417068
TI - Photoacoustic in vitro flow cytometry for nanomaterial research.
AB - Conventional flow cytometry is a versatile tool for drug research and cell
characterization. However, it is poorly suited for quantification of non
fluorescent proteins and artificial nanomaterials without the use of additional
labeling. The rapid growth of biomedical applications for small non-fluorescent
nanoparticles (NPs) for drug delivery and contrast and therapy enhancement, as
well as research focused on natural cell pigments and chromophores, demands high
throughput quantification methods for the non-fluorescent components. In this
work, we present a novel photoacoustic (PA) fluorescence flow cytometry (PAFFC)
platform that combines NP quantification though PA detection with conventional in
vitro flow cytometry sample characterization using fluorescence labeling. PAFFC
simplifies high-throughput analysis of cell-NP interactions, optimization of
targeted nanodrugs, and NP toxicity assessment, providing a direct correlation
between NP uptake and characterization of toxicity markers for every cell.
PMID- 28417070
TI - Acute bacteremic pneumonia due to melioidosis developing in the intensive care
setting.
AB - In Malaysia, melioidosis is commonly encountered as this infection is known as
part of the endemic area for the disease. Managing cases of positive Burkholderia
pseudomallei infection can involve multidisciplinary unit mainly, microbiologist,
infectious disease team and intensive care as it may be quite difficult to
distinguish melioidosis from a number of other diseases on the clinical setting
alone. Laboratory diagnosis plays a vital role in determining the direction of
management. Investigations such as culture, polymerase chain reaction (PCR) and
serology should be evaluated once the disease is suspected. In this particular
case, the patient is a young adult involved in a road traffic accident. Unlike
any other cases with melioidosis, he had no potential risk factors which may have
contributed to the severity of the disease and it is likely that the site of the
accident was the source of acquisition of this gram negative bacterium.
PMID- 28417069
TI - Clostridium difficile bacteremia: Report of two cases in French hospitals and
comprehensive review of the literature.
AB - We report two cases of bacteremia due to Clostridium difficile from two French
hospitals. The first patient with previously diagnosed rectal carcinoma underwent
courses of chemotherapy, and antimicrobial treatment, and survived the C.
difficile bacteremia. The second patient with colon perforation and newly
diagnosed lung cancer underwent antimicrobial treatment in an ICU but died
shortly after the episode of C. difficile bacteremia. A review of the literature
allowed the identification of 137 cases of bacteremia between July 1962 and
November 2016. Advanced age, gastro-intestinal disruption, severe underlying
diseases and antimicrobial exposure were the major risk factors for C. difficile
bacteremia. Antimicrobial therapy was primarily based on metronidazole and/or
vancomycin. The crude mortality rate was 35% (21/60).
PMID- 28417071
TI - Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi
Arabian patients with maple syrup urine disease.
AB - Maple syrup urine disease (MSUD), an autosomal recessive inborn error of
metabolism due to defects in the branched-chain alpha-ketoacid dehydrogenase
(BCKD) complex, is commonly observed among other inherited metabolic disorders in
the kingdom of Saudi Arabia. This report presents the results of mutation
analysis of three of the four genes encoding the BCKD complex in 52 biochemically
diagnosed MSUD patients originating from Saudi Arabia. The 25 mutations (20
novel) detected spanned across the entire coding regions of the BCKHDA, BCKDHB
and DBT genes. There were no mutations found in the DLD gene in this cohort of
patients. Prediction effects, conservation and modelling of novel mutations
demonstrated that all were predicted to be disease-causing. All mutations
presented in a homozygous form and we did not detect the presence of a "founder"
mutation in any of three genes. In addition, prenatal molecular genetic testing
was successfully carried out on chorionic villus samples or amniocenteses in 10
expectant mothers with affected children with MSUD, molecularly characterized by
this study.
PMID- 28417072
TI - Atypical juvenile presentation of GM2 gangliosidosis AB in a patient compound
heterozygote for c.259G > T and c.164C > T mutations in the GM2A gene.
AB - GM2-gangliosidosis, AB variant is an extremely rare autosomal recessive inherited
disorder caused by mutations in the GM2A gene that encodes GM2 ganglioside
activator protein (GM2AP). GM2AP is necessary for solubilisation of GM2
ganglioside in endolysosomes and its presentation to beta-hexosaminidase A.
Conversely GM2AP deficiency impairs lysosomal catabolism of GM2 ganglioside,
leading to its storage in cells and tissues. We describe a 9-year-old child with
an unusual juvenile clinical onset of GM2-gangliosidosis AB. At the age of 3
years he presented with global developmental delay, progressive epilepsy,
intellectual disability, axial hypertonia, spasticity, seizures and ataxia, but
without the macular cherry-red spots typical for GM2 gangliosidosis. Brain MRI
detected a rapid onset of diffuse atrophy, whereas whole exome sequencing showed
that the patient is a compound heterozygote for two mutations in GM2A: a novel
nonsense mutation, c.259G > T (p.E87X) and a missense mutation c.164C > T
(p.P55L) that was recently identified in homozygosity in patients of a Saudi
family with a progressive chorea-dementia syndrome. Western blot analysis showed
an absence of GM2AP in cultured fibroblasts from the patient, suggesting that
both mutations interfere with the synthesis and/or folding of the protein.
Finally, impaired catabolism of GM2 ganglioside in the patient's fibroblasts was
demonstrated by metabolic labeling with fluorescently labeled GM1 ganglioside and
by immunohistochemistry with anti-GM2 and anti-GM3 antibodies. Our observation
expands the molecular and clinical spectrum of molecular defects linked to GM2
gangliosidosis and suggests novel diagnostic approach by whole exome sequencing
and perhaps ganglioside analysis in cultured patient's cells.
PMID- 28417073
TI - Primary Amyloidosis of the Urinary Bladder: A Case Report.
AB - Primary amyloidosis of the urinary bladder is a rare disease, with only
approximately 200 cases reported in the literature. We herein present a case of
amyloidosis of the urinary bladder with painful gross hematuria. Pelvic Computed
Tomography showed uneven thickening of the bladder wall suspicious of neoplastic
lesion. Cystoscopy and transurethral resection were performed. Congo-red staining
confirmed amyloidosis it was. Postoperative recovery was good and close follow-up
was recommended after discharged. Amyloidosis is usually benign, while it can
masquerade as a malignancy. Doctors should consider it when imaging studies
reveal a malignancy in bladder.
PMID- 28417074
TI - Renal Leiomyoma: A Case Report and Review of the Literature.
AB - Leiomyoma is an uncommon tumor of the kidney. The authors report a rare case of
renal leiomyoma in a 39-year-old male patient who presented with a right flank
mass. Laparoscopic nephrectomy was performed. The histopathology and
immunohistochemistry confirm the diagnosis of renal leiomyoma. The review of
literature in the clinicoradiopathological correlation was illustrated.
PMID- 28417075
TI - Giant Ureteral Fibroepithelial Polyp with Intermittent Prolapse Reaching the
Urethral Meatus: A Case Report.
AB - Ureteral fibroepithelial polyps (UFPs) are rare non-epithelial benign tumors of
the urinary tract. Treatment of such cases ranges from conservative management to
surgical resection of the polyp. Hereby, we present a rare case of a 37-year-old
female patient with giant 14 cm UFP of the distal left ureter, successfully
resected by ureteroscopic electrocauterization. Several cases of UFPs have been
previously reported in world literature describing polyps extending into the
bladder; yet, our case is the first to present a giant UFP that extends beyond
the bladder cavity protruding outside the urethral meatus as a red fleshy mass.
PMID- 28417076
TI - The Case of Huge Pure Lipoma of the Spermatic Cord Misdiagnosed as Inguinal
Hernia.
AB - Clinically, pure spermatic-cord lipoma has not been recognized as a disease
entity but regarded as an incidental finding at the time of hernia repair,
because it presents groin symptoms and clinical findings indistinguishable from
those of inguinal hernia. We report the successful treatment of case of huge pure
spermatic-cord lipoma originally misdiagnosed as inguinal hernia. The patients
had tumor excision without orchiectomy. Symptoms improved without any
complication. In patients with inguinal hernia symptoms, pure spermatic-cord
lipoma should be recognized as a significant clinical entity, and differential
diagnosis should be achieved using ultrasonography and computed tomography to
avoid unnecessary hernia repair.
PMID- 28417077
TI - Direct Extension of Prostatic Adenocarcinoma Protruding Through the Urethral
Meatus.
AB - Prostate cancer involving the anterior urethra is rare with few cases describing
isolated recurrence to the anterior urethra. This case describes a patient with a
history of metastatic prostate cancer who subsequently developed advanced
prostate cancer involving the entire urethra with extension from the prostatic
urethra to the urethral meatus. This will help future healthcare providers
recognize this metastatic pattern as a possibility and explore this option when
presented with a bleeding mass at the urethral meatus of unknown origin. It is
important for clinicians to realize poorly differentiated prostate cancer may not
produce PSA yet still behave aggressively.
PMID- 28417078
TI - Local Excision for the Treatment of Penile Verrucous Carcinoma.
AB - Penile verrucous carcinoma is known for its favorable biologic behavior and lack
of metastatic potential. For preservation of function, treatment has been focused
on partial penectomy. Despite partial penectomy for preservation of minimal
functional and aesthetic aspects, patients have experienced psychosexual
problems. A 73-year-old man had a cauliflower-like verrucous carcinoma on the
penile glans and coronary sulcus diagnosed by using excisional biopsy. He
underwent degloving excision to save the penile shaft and glans penis. Surgical
margin was 3 mm. He had been tumor-free at the 2-year follow-up. For maximum
preservation of the functional and aesthetic aspects, we recommend degloving
excision.
PMID- 28417079
TI - Detection of copy number alterations in cell-free tumor DNA from plasma.
AB - BACKGROUND: Somatic copy number alterations (SCNAs) occurring in tumors can
provide information about tumor classification, patient's outcome or treatment
targets. Liquid biopsies, incl. plasma samples containing circulating cell-free
tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however
specify and reliability of methods have to be tested. METHODS: SNP microarrays
(Affymetrix) were used to generate whole-genome copy number profiles from plasma
ccfDNA (OncoScan) and paired tumor biopsies (CytoScan) from ten patients with
metastatic cancers. Numerical, segmental and focal SCNAs were assessed using
ASCAT/TuScan and SNP-FASST2. RESULTS: Aberrations in ccfDNA in 4 patients
resembled numerical (76%) and segmental (80%) aberrations in tDNA. Three patients
represented low correlation due to postponed sampling time, ccfDNA quality and
possible treatment interference. Breakpoints of high-amplitude amplification were
assessed with high accuracy and relative breakpoints difference of only 7% (0.02
37%). Similarly, biallelic losses were reliably detected. Array was 100%
successful in detection of SCNAs on clinically relevant genes compared to SCNAs
in tumor biopsies. Tracking of SCNAs changes during the treatment course of one
patient also indicated that apoptosis/necrosis of non-cancerous cells presumably
induced by treatment can influence ccfDNA composition and introduce false
negative findings into the analysis of liquid biopsies. CONCLUSIONS: Genomic
alterations detected in ccfDNA from liquid biopsies by comprehensive SNP array
are reliable source for information for stratification of patients for targeted
treatment. GENERAL SIGNIFICANCE: Clinically relevant SCNAs can be detected in
ccfDNA with high resolution and can therefore serve as an alternative to tumor
biopsy in defining treatment targets.
PMID- 28417081
TI - An ELISA protocol to improve the accuracy and reliability of serological antibody
assays.
AB - To assay serum antibodies by indirect ELISA, it is critical to eliminate a
variety of false positive and negative reactions attributed to the principle.
These include 1) the background (BG) noise reaction caused by hydrophobic binding
of immunoglobulin components in sample specimens to solid surfaces, 2) false
positive reaction caused by non-specific binding of immunoglobulins to target
antigens by protein-protein interactions, and 3) other false positive and
negative reactions caused by buffer components. No current blocking agents can
prevent these false positive and negative reactions, and antibody assay results
vary significantly depending on the buffer system used. To address these
fundamental problems, we investigated all types of non-specific reactions
involved in indirect ELISAs, and the blocking efficacy of current buffer systems
and a newly developed ELISA buffer, ChonBlockTM. The accuracy and reliability of
these assay results were examined in detail by inhibition tests in individual
buffer systems. Based on these studies, we are providing a definitive ELISA
protocol for all users to improve ELISA technique and obtain accurate, reliable,
and reproducible assay data against a variety of antigens.
PMID- 28417082
TI - Improving glucose tolerance by muscle-damaging exercise.
AB - : Tissue damage is regarded as an unwanted medical condition to be avoided.
However, introducing tolerable tissue damages has been used as a therapeutic
intervention in traditional and complementary medicine to cure discomfort and
illness. Eccentric exercise is known to cause significant necrosis and insulin
resistance of skeletal muscle. The purpose of this study was to determine the
magnitude of muscle damage and blood glucose responses during an oral glucose
tolerance test (OGTT) after eccentric training in 21 young participants. They
were challenged by 5 times of 100-meter downhill sprinting and 20 times of squats
training at 30 pounds weight load for 3 days, which resulted in a wide spectrum
of muscle creatine kinase (CK) surges in plasma, 48 h after the last bout of
exercise. Participants were then divided into two groups according the magnitude
of CK increases (low CK: +48% +/- 0.3; high CK: +137% +/- 0.5, P < 0.05). Both
groups show comparable decreases in blood glucose levels in OGTT, suggesting that
this muscle-damaging exercise does not appear to decrease but rather improve
glycemic control in men. CONCLUSION: The result of the study rejects the
hypothesis that eccentric exercise decreases glucose tolerance. Improved glucose
tolerance with CK increase implicates a beneficial effect of replacing
metabolically weaker muscle fibers by eccentric exercise in Darwinian natural
selection fashion.
PMID- 28417080
TI - Applying a systems approach to thyroid physiology: Looking at the whole with a
mitochondrial perspective instead of judging single TSH values or why we should
know more about mitochondria to understand metabolism.
AB - : Classical thinking in endocrine physiology squeezes our diagnostic handling
into a simple negative feedback mechanism with a controller and a controlled
variable. In the case of the thyroid this is reduced to TSH and fT3 and fT4,
respectively. The setting of this tight notion has no free space for any
additions. In this paper we want to challenge this model of limited application
by proposing a construct based on a systems approach departing from two basic
considerations. In first place since the majority of cases of thyroid disease
develop and appear during life it has to be considered as an acquired condition.
In the second place, our experience with the reversibility of morphological
changes makes the autoimmune theory inconsistent. While medical complexity can
expand into the era of OMICS as well as into one where manipulations with the use
of knock-outs and -ins are common in science, we have preferred to maintain a
simple and practical approach. We will describe the interactions of iron,
magnesium, zinc, selenium and coenzyme Q10 with the thyroid axis. The discourse
will be then brought into the context of ovarian function, i.e. steroid hormone
production. Finally the same elemental players will be presented in relation to
the basic mitochondrial machinery that supports the endocrine. We propose that an
intact mitochondrial function can guard the normal endocrine function of both the
thyroid as well as of the ovarian axis. The basic elements required for this
function appear to be magnesium and iron. In the case of the thyroid, magnesium
ATP acts in iodine uptake and the heme protein peroxidase in thyroid hormone
synthesis. A similar biochemical process is found in steroid synthesis with
cholesterol uptake being the initial energy-dependent step and later the heme
protein ferredoxin 1 which is required for steroid synthesis. Magnesium plays a
central role in determining the clinical picture associated with thyroid disease
and is also involved in maintaining fertility. With the aid of 3D sonography
patients needing selenium and/or coenzyme Q10 can be easily identified. By this
we firmly believe that physicians should know more about basic biochemistry and
the way it fits into mitochondrial function in order to understand metabolism.
Contemplating only TSH is highly reductionistic. OUTLINE: *Author's profiles and
motivation for this analysis*The philosophical alternatives in science and
medicine*Reductionism vs. systems approach in clinical thyroid disease
guidelines*The entry into complexity: the involvement of the musculoskeletal
system*Integrating East and West: teachings from Chinese Medicine and from
evidence based medicine (EBM)*Can a mathematical model represent complexity in
the daily thyroid practice?*How effective is thyroxine treatment?*Resolving the
situation of residual symptoms in treated patients with thyroid
disease*Importance of iron, zinc and magnesium in relation to thyroid
function*Putting together new concepts related to thyroid function for a systems
approach*Expanding our model into general aspects of medicine.
PMID- 28417083
TI - Effects of turmeric curcuminoids and metformin against central sensitivity to
pain in mice.
AB - The reported experimental study was conducted to compare the effects of repeated
daily oral doses of curcuminoids (CLE) with metformin as potential
antidepressants and analgesics. Effects of a single and ten daily oral doses of
CLE (5, 20, 80 mg/kg/day) and of 50 mg/kg/day metformin (MET) were compared in
mice hot plate test (HPT) for analgesics. On the 11th treatment day, all animals
were subjected to foot shock stress triggered hyperthermia test, and on the 12th
treatment day to tail suspension test (TST) for antidepressants. Immediately
thereafter, their blood levels of glucose, insulin and cortisol were quantified.
Dose dependent analgesic activity of CLE was observed in HPT, whereas the
metformin dose tested suppressed only pain hypersensitivity in the test. But
statistically significant effects of both of them were observed in TST, and both
of them also afforded protections against body weight loss and slight elevation
in core temperatures induced by daily handling and repeated testing. CLE or
metformin had no significant effects in foot shock stress triggered transient
hyperthermic responses or on blood glucose, insulin and cortisol levels. Reported
results reveal that curcuminoids as well as metformin are stress response
modifiers with antidepressants like activities, but only low dose curcuminoids
possess centrally acting analgesics like activities. They suggest that the bio
assay system used in this study is well suited for identifying curcuminoids like
plant metabolites with analgesic and anti-stress activities, and that low dose
curcuminoids are more effective as analgesics than low dose metformin.
PMID- 28417084
TI - Antioxidant, antimicrobial activity and bioactive compounds of Bergenia ciliata
Sternb.: A valuable medicinal herb of Sikkim Himalaya.
AB - Bergenia ciliata Sternb., commonly known as Paashaanbhed, is a well known herb of
Sikkim Himalaya with various pharmaceutical properties. However, scientific
exploration of B. ciliata, growing in the Sikkim Himalaya, for phytochemicals and
pharmacological properties is in infancy. With this view, the present study was
undertaken to investigate B. ciliata leaf extracts for antioxidant, antimicrobial
activity and bioactive compounds. Three solvents viz., methanol, ethyl acetate
and hexane were used for extraction and the respective leaf extracts were
analyzed for total phenolic and flavonoid contents along with the antioxidant and
antimicrobial activities. Amongst the tested solvents, methanol was found to be
the best solvent for extraction with highest total phenolic contents and the
lowest IC50 values for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino
bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Methanol extract also
exhibited effective antimicrobial activity, particularly against bacteria and
actinomycetes. Further, high performance liquid chromatography (HPLC) analysis
revealed that methanolic extract contains the highest amount of all the three
analyzed bioactive compounds viz. bergenin, catechin and gallic acid. The current
study suggests that the methanol extract of B. ciliata is a potential source of
natural antioxidant and antimicrobial compounds that can be used in food and drug
industries.
PMID- 28417085
TI - Hepatoprotective standardized EtOH-water extract from the seeds of Fraxinus
rhynchophylla Hance.
AB - Fraxinus rhynchophylla Hance (Oleaceae), its stem barks are known as Cortex
fraxini ( qin pi) listed in Chinese Pharmacopoeia. Phytochemical study has
indicated that methanol extracts from Qinpi has protective effect on acute liver
injury. The present study investigates the hepatoprotective activity of EtOH
water extract from the seeds of F. rhynchophylla Hance against carbon
tetrachloride-induced liver injury in mice. The EtOH-water extract significantly
alleviated liver damage as indicated by the decreased levels of serum alanine
aminotransferase (ALT) and aspartate aminotransferase (AST), the malondialdehyde
(MDA) content, and increased the levels of superoxide dismutase (SOD),
glutathione (GSH) and glutathione peroxidase (GSH-Px), and reduced the
pathological tissue injury induced by CCl4. Quantitative analysis of seven major
constituents (1-7) in EtOH-water extract (EWE) was developed by high performance
liquid chromatography-diode-array detector (HPLC-DAD). The current research
indicates that the EWE from the seeds of F. rhynchophylla Hance decreased liver
index, inhibited the increase of serum aminotransferase induced by CCl4, and
decreased hepatic MDA content, SOD and GSH-Px activities. These results suggested
that the pretreatment with EWE protected mice against CCl4-induced liver
injuries. Based on the results, the EtOH-water extract from the seeds of F.
rhynchophylla Hance is efficacious for prevention and treatment of CCl4-induced
hepatic injury in mice. Secoiridoid and tyrosol glucosides might be the active
ingredients responsible for the biological and pharmacological activities of
hepatoprotection.
PMID- 28417086
TI - Blood immune function parameters in response to combined aerobic dance exercise
and honey supplementation in adult women.
AB - To date, information on the effectiveness of combined aerobic dance exercise with
honey supplementation on immune function in women is lacking. The present study
investigated the effects of 8 weeks of combined aerobic dance exercise and honey
supplementation on blood immune function parameters in adult women. In this
study, forty four healthy sedentary women (25-40 year-old) were assigned into
four groups with n = 11 per group: sedentary without supplementation control
(Con), honey supplementation (H), aerobic dance exercise (D) and combined aerobic
dance exercise with honey supplementation (HD) groups. Aerobic dance exercise was
carried out for one hour per session, three sessions per week for eight weeks.
Honey drink was consumed by H and HD groups, in a dosage of 20 g of honey diluted
in 300 ml of plain water, consumed 7 days a week for 8 weeks. In HD group, the
participants were required to consume honey drink 30 min before performing
exercise. Before and after 8 weeks of experimental period, blood samples were
taken to determine the concentrations of immune parameters which include full
blood counts and immunophenotyping measurements. It was found that after 8 weeks
of experimental period, there were statistically significant increases in T
cytotoxic (CD8) (p < 0.05) in HD group. Additionally, the percentages increase in
total lymphocyte counts, T helper (CD4), and T cytotoxic (CD8) counts after 8
weeks were the highest in HD group among all the groups. As conclusion, combined
aerobic dance and honey supplementation may have potential to enhance immune
functions in women.
PMID- 28417087
TI - Screening for antibacterial and antibiofilm activity in Thai medicinal plant
extracts against oral microorganisms.
AB - To evaluate the antibacterial activity of 12 ethanol extracts of Thai traditional
herb against oral pathogens. The antibacterial activities were assessed by agar
well diffusion, broth microdilution, and time-kill methods. Antibiofilm activity
was investigated using a 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium
bromide (MTT) assay. High performance liquid chromatography (HPLC), thin layer
chromatography (TLC) fingerprinting, and TLC-bioautography were used to determine
the active antibacterial compounds. Piper betle showed the best antibacterial
activities against all tested strains in the minimal inhibitory concentration and
minimal bactericidal concentration, ranged from 1.04-5.21 mg/mL and 2.08-8.33
mg/mL, respectively. Killing ability depended on time and concentrations of the
extract. P. betle extract acts as a potent antibiofilm agent with dual actions,
preventing and eradicating the biofilm. The major constituent of P. betle extract
was 4-chromanol, which responded for antibacteria and antibiofilm against oral
pathogens. It suggests that the ethanol P. betle leaves extract may be used for
preventing oral diseases.
PMID- 28417088
TI - Boiling-induced nanoparticles and their constitutive proteins from Isatis
indigotica Fort. root decoction: Purification and identification.
AB - Colloidal particles are essential components of sun-dried Isatis indigotica Fort.
roots (Ban-Lan-Gen in Chinese, BLG) decoction. Nanoparticles (NPs) were isolated
from BLG decoction with size exclusion chromatography and characterized. Their
average diameter is ~120 nm, reversibly responding to pH and temperature changes.
They promoted the growth of normal cells but suppressed that of cancerogenic
cells and macrophages. Two constitutive glycated proteins were identified from
the NPs, namely BLGP1 and BLGP2. Their N-terminal amino acid sequences were V-X-R
E-V-V-K-D-I and V-V-R-E-V-V-K-D-I-A-G-A-V-Q-T-N-E-Q-Y. Their full-length cDNA
sequences were cloned to obtain the highly homological amino acid sequences of
non-glycated proteins, whose theoretical molecular weights are 21831.64 Da and
21841.67 Da. Using pepsin hydrolysis and mass spectrometry, four possible
glycation adducts were identified in BLGP1, whereas one in BLGP2. To conclude,
bioactive nanoparticles isolated from the herbal decoction are intelligent
nanoassemblies composed of a new boiling-stable protein. Glycation plays a
critical role in heat-induced formation of these nanoassemblies. The novel,
intelligent, safe and stable nano-carriers for drug delivery may be developed
using BLG NPs as prototype.
PMID- 28417089
TI - Demographic and medication characteristics of traditional Chinese medicine users
among colorectal cancer survivors: A nationwide database study in Taiwan.
AB - Chinese herbal product (CHP) is the major type of traditional Chinese medicine
(TCM) and widely used to relief the symptom of colorectal cancer. The aim of the
study was to analyze the utilization of CHP for treating patients with colorectal
cancer in Taiwan. The usage of CHP, frequency of services, and prescription
pattern for colorectal cancer were analyzed from a randomly sampled cohort of 1
million beneficiaries from the National Health Insurance Research Database. The
odds ratios for utilization of CHP were estimated with logistic regression model.
2846 patients were newly diagnosed as colorectal cancer during 1998-2008 in the
million cohort in Taiwan. 42.7% (n = 1214) of them used CHP. Colorectal cancer
was the most common diagnosis coded by TCM doctor, followed by symptoms, signs,
and ill-defined conditions. Costusroot and Amomum Six Gentlemen Decoction ( xiang
sha liu jun zi tang) was the most frequently prescribed formula for treating
colorectal cancer. Among the top 10 most frequently prescribed CHP for treating
colorectal cancer, six containing Ginseng Radix (, Panax ginseng) and two
containing Astragali Radix (, Astragalus membranaceus), which are reported to
have potential beneficial synergistic effects on colorectal cancer cells. CHP
containing Ginseng Radix or Astragali Radix are the most frequently prescribed
for colorectal cancer and their effects should be taken into account by
healthcare providers.
PMID- 28417092
TI - Revival, modernization and integration of Indian traditional herbal medicine in
clinical practice: Importance, challenges and future.
AB - In spite of incredible advances in modern science, technology and allopathic
medicine a large we are unable to provide quality healthcare to all. Traditional
medicine particularly herbal medicine considered as a major healthcare provider
around the globe particularly in rural and remote areas. A large section of
people depends on such medicine for their primary healthcare mainly in
underdeveloped or developing countries. Indian traditional medicinal system like
Ayurveda, Siddha and Unani has a very rich history of their effectiveness; modern
research also acknowledged the importance of such medicine. Indian traditional
medicine or medicinal plants are also considered as a vital source of new drug.
Mainstreaming of such medicine is important for the people. Several steps have
been taken in India to promote such medicine and to integrate them into clinical
practice. Evidence based incorporation of Indian traditional medicine in clinical
practice will help to provide quality healthcare to all.
PMID- 28417090
TI - Role of traditional Islamic and Arabic plants in cancer therapy.
AB - ETHNO PHARMACOLOGICAL RELEVANCE: This review article underlines individual
Traditional Islamic and Arabic plant (TAI) and their role in treating cancer. The
aim of the study is to specifically evaluate the progress of herbs, Arabic and
Islamic traditional herbs in particular, applied in cancer treatment, so far.
MATERIALS AND METHODS: Islamic and Arabic plants were selected and identified
through different literature survey using "Google scholar", "Web of science",
"Scopus" and "PubMed". Each plant, from identified Arabic and Islamic plants
list, was search individually for the most cited articles in the aforementioned
databases using the keywords, "Anticancer", "Uses in cancer treatment", "Ethno
pharmacological importance in cancer" etc. RESULTS: The current review about
Islamic and Arabic plants illuminates the importance of Islamic and Arabic plants
and their impact in treating cancer. There is a long list of Islamic and Arabic
plants used in cancer as mentioned in review with enormous amount of literature.
Each plant has been investigated for its anticancer potential. The literature
survey as mentioned in table shows; these plants are widely utilized in cancer as
a whole, a part thereof or in the form of isolated chemical constituent.
CONCLUSIONS: This review strongly supports the fact; Arabic and Islamic
traditional plants have emerged as a good source of complementary and alternative
medicine in treating cancer. Traditional Arab-Islamic herbal-based medicines
might be promising for new cancer therapeutics with low toxicity and minimal side
effects. The plants used are mostly in crude form and still needs advance
research for the isolation of phytochemicals and establishing its cellular and
molecular role in treating cancer.
PMID- 28417091
TI - Biological activities of curcuminoids, other biomolecules from turmeric and their
derivatives - A review.
AB - In recent years, several drugs have been developed deriving from traditional
products and current drug research is actively investigating the possible
therapeutic roles of many Ayruvedic and Traditional Indian medicinal therapies.
Among those being investigated is Turmeric. Its most important active ingredient
is curcuminoids. Curcuminoids are phenolic compounds commonly used as a spice,
pigment and additive also utilized as a therapeutic agent used in several foods.
Comprehensive research over the last century has revealed several important
functions of curcuminoids. Various preclinical cell culture and animals studies
suggest that curcuminoids have extensive biological activity as an antioxidant,
neuroprotective, antitumor, anti-inflammatory, anti-acidogenic, radioprotective
and arthritis. Different clinical trials also suggest a potential therapeutic
role for curcuminoids in numerous chronic diseases such as colon cancer, lung
cancer, breast cancer, inflammatory bowel diseases. The aim of this review is to
summarize the chemistry, analog, metal complex, formulations of curcuminoids and
their biological activities.
PMID- 28417093
TI - Instability resistance training for health and performance.
AB - Recently, resistance exercises performed on an unstable surface have become part
of athletic training and rehabilitation. Accordingly, their role in performance
and health-oriented strength training has increasingly emerged as a matter of
interest to researchers and conditioning specialists. A more pronounced
activation of stabilizing muscles is assumed to be the main feature of
instability resistance exercises. This assumption has been proven by EMG studies,
which have highlighted significantly greater electromyographic activity of trunk
stabilizing muscles during exercises under unstable as compared to stable
conditions. Intervention studies also demonstrated an enhanced improvement of
trunk stability after training programs utilizing unstable devices as compared to
floor exercises. Findings indicate that instability resistance training may
facilitate the neural adaptation of trunk-stabilizing muscles, resulting in an
improvement in trunk stability. However, both acute and long-term responses of
primarily activated muscles to exercises performed on an unstable surface remain
a matter of debate. It has been established that there is a significantly lower
peak isometric force and rate of force development during resistance exercises
under unstable as compared to stable conditions. In addition, the power output
was compromised when exercises were performed on unstable surfaces. However, we
have demonstrated that this effect depends on the type of exercise, instability
device used, weight lifted, subject's training background, and so forth. Our
findings on muscular power in the concentric phase of resistance exercises with
different weights under stable and unstable conditions complement this review.
Applications of instability resistance exercises for the improvement of
neuromuscular functions in the physically active, plus for those following
anterior cruciate ligament reconstructions, are also presented.
PMID- 28417095
TI - A visual grid to digitally record an Ayurvedic Prakriti assessment; a first step
toward integrated electronic health records.
PMID- 28417096
TI - Regulation of herbal medicine use based on speculation? A case from Sri Lanka.
AB - Chronic Kidney Disease of Unknown aetiology is a significant public health
problem in Sri Lanka. The final report by the WHO mission recommended regulation
of herbal medicines containing aristolochic acid, which is an established
nephrotoxin. The use of Complimentary and Alternative Medicine (CAM) has a
history of more than 2500 years in Sri Lanka. Aristolochia species are rarely
used in Ayurveda and traditional medicine in Sri Lanka. Before regulating the
analysis of herbal preparations using Aristolochia, collecting data from CAM
practitioners regarding the use of Aristolochia is necessary. Analysis of
Ayurveda pharmacopeia shows the doses used are negligible and some preparations
are used for external applications.
PMID- 28417097
TI - Zika-related microcephaly in experimental models.
PMID- 28417094
TI - Contemporary acupressure therapy: Adroit cure for painless recovery of
therapeutic ailments.
AB - Since time immemorial, complementary and alternative medicines (CAM) have played
a significant role in human health care. CAM is known to have a strong reputation
and reliability within every culture to provide basic health care treatment for
patients. CAM acts as a better therapeutic option in human being for treating
various diseases and improving quality of life with apt consideration to the
economic aspects. Acupressure, one of the known CAM, originated in ancient China
is based on the principal of acupoints activation across the meridians which
correct the imbalance between Qi. Activation of specific points on the meridians
is known to facilitate reduction of pain at the local sites. It also reduces the
pain from other body parts. This review outlines various types, devices and
mechanisms involved in the acupressure treatment.
PMID- 28417098
TI - Avoiding apoptosis during mammalian hibernation.
PMID- 28417099
TI - Data for transcriptomic and proteomic analyses of leaves from Clematis terniflora
DC. under binary stress.
AB - High level of UV-B irradiation followed by dark treatment accumulates secondary
metabolites in Clematis terniflora DC. To investigate the response mechanism
under high level of UV-B irradiation followed by dark treatment, transcriptomic
and proteomic analyses were performed in leaves of Clematis terniflora DC. The
experimental design for the transcriptomic and proteomic analyses in leaves of C.
terniflora under stresses was organized into a picture. For transcriptomics, mRNA
sequencing technology was used. Genes identified in leaves of C. terniflora at
starting point, high level of UV-B irradiation, and high level of UV-B
irradiation followed by dark treatment were listed; genes with different
expression levels at starting point, high level of UV-B irradiation, and high
level of UV-B irradiation followed by dark treatment were also presented in this
DiB article. For proteomics, a gel-free/label-free proteomic technique was used.
Proteins with different abundances in leaves at starting point, high level of UV
B irradiation, and high level of UV-B irradiation followed by dark treatment were
presented in this DiB article. In order to monitor the expression levels of genes
under the stress, quantitative reverse transcription polymerase chain reaction
was performed. The primer sequences of genes selected for quantitative reverse
transcription polymerase chain reaction was presented in this DiB article.
PMID- 28417100
TI - Data for TROTS - The Radiotherapy Optimisation Test Set.
AB - The Radiotherapy Optimisation Test Set (TROTS) is an extensive set of problems
originating from radiotherapy (radiation therapy) treatment planning. This
dataset is created for 2 purposes: (1) to supply a large-scale dense dataset to
measure performance and quality of mathematical solvers, and (2) to supply a
dataset to investigate the multi-criteria optimisation and decision-making nature
of the radiotherapy problem. The dataset contains 120 problems (patients),
divided over 6 different treatment protocols/tumour types. Each problem contains
numerical data, a configuration for the optimisation problem, and data required
to visualise and interpret the results. The data is stored as HDF5 compatible
Matlab files, and includes scripts to work with the dataset.
PMID- 28417101
TI - Role of Active Listening and Listening Effort on Contralateral Suppression of
Transient Evoked Otoacousic Emissions.
AB - BACKGROUND AND OBJECTIVES: The present study aimed to investigate the effect of
active listening and listening effort on the contralateral suppression of
transient evoked otoacoustic emissions (CSTEOAEs). SUBJECTS AND METHODS: Twenty
eight young adults participated in the study. Transient evoked otoacoustic
emissions (TEOAEs) were recorded using 'linear' clicks at 60 dB peSPL, in three
contralateral noise conditions. In condition 1, TEOAEs were obtained in the
presence of white noise in the contralateral ear. While, in condition 2, speech
was embedded into white noise at +3, -3, and -9 dB signal-to-noise ratio (SNR)
and delivered to the contralateral ear. The SNR was varied to investigate the
effect of listening effort on the CSTEOAE. In condition 3, speech was played
backwards and embedded into white noise at -3 dB SNR. The conditions 1 and 3
served as passive listening condition and the condition 2 served as active
listening condition. In active listening condition, the participants categorized
the words in to two groups (e.g., animal and vehicle). RESULTS: CSTEOAE was found
to be largest in the presence of white noise, and the amount of CSTEOAE was not
significantly different between active and passive listening conditions
(condition 2 and 3). Listening effort had an effect on the CSTEOAE, the amount of
suppression increased with listening effort, when SNR was decreased from +3 dB to
-3 dB. However, when the SNR was further reduced to -9 dB, there was no further
increase in the amount of CSTEOAE, instead there was a reduction in the amount of
suppression. CONCLUSIONS: The findings of the present study show that listening
effort might affect CSTEOAE.
PMID- 28417102
TI - Prognostic Factors for Recovery from Sudden Sensorineural Hearing Loss: A
Retrospective Study.
AB - BACKGROUND AND OBJECTIVES: This study aimed to investigate prognostic factors in
patients with idiopathic sudden sensorineural hearing loss (ISSNHL). SUBJECTS AND
METHODS: From January 2007 to December 2011, a retrospective chart review
identified 494 consecutive patients with ISSNHL. Demographic, audiometric, and
clinical data were analyzed using a logistic regression test. RESULTS: Hearing
recovery from ISSNHL was significantly associated with factors such as age,
duration from onset of symptoms to commencement of treatment, severity of the
initial pure tone threshold, and the treatment method. Intratympanic (IT) steroid
administration alone showed a comparable efficiency to oral steroid
administration with or without IT steroid injection. In patients who received IT
steroid injection, the duration from onset to treatment, severity of initial
hearing loss, and sequential IT steroid injection following systemic steroid
administration were statistically associated with hearing improvement.
CONCLUSIONS: Age, severity of initial pure tone threshold, duration from onset to
treatment, initial speech discrimination, and initial pure tone threshold are
statistically significant prognostic factors related to hearing improvement in
ISSNHL. IT steroid injection as an initial single treatment is comparable to
systemic oral steroid administration.
PMID- 28417103
TI - Effect of Age and Severity of Facial Palsy on Taste Thresholds in Bell's Palsy
Patients.
AB - BACKGROUND AND OBJECTIVES: To investigate whether taste thresholds, as determined
by electrogustometry (EGM) and chemical taste tests, differ by age and the
severity of facial palsy in patients with Bell's palsy. SUBJECTS AND METHODS:
This study included 29 patients diagnosed with Bell's palsy between January 2014
and May 2015 in our hospital. Patients were assorted into age groups and by
severity of facial palsy, as determined by House-Brackmann Scale, and their taste
thresholds were assessed by EGM and chemical taste tests. RESULTS: EGM showed
that taste thresholds at four locations on the tongue and one location on the
central soft palate, 1 cm from the palatine uvula, were significantly higher in
Bell's palsy patients than in controls (p<0.05). In contrast, chemical taste
tests showed no significant differences in taste thresholds between the two
groups (p>0.05). The severity of facial palsy did not affect taste thresholds, as
determined by both EGM and chemical taste tests (p>0.05). The overall mean
electrical taste thresholds on EGM were higher in younger Bell's palsy patients
than in healthy subjects, with the difference at the back-right area of the
tongue differing significantly (p<0.05). In older individuals, however, no
significant differences in taste thresholds were observed between Bell's palsy
patients and healthy subjects (p>0.05). CONCLUSIONS: Electrical taste thresholds
were higher in Bell's palsy patients than in controls. These differences were
observed in younger, but not in older, individuals.
PMID- 28417104
TI - Combined Bifrontal Transcranial Direct Current Stimulation and Tailor-Made
Notched Music Training in Chronic Tinnitus.
AB - BACKGROUND AND OBJECTIVES: We evaluated the short-term treatment outcomes of
combined bifrontal transcranial direct current stimulation (tDCS) and tailor-made
notched music training (TMNMT) in tinnitus patients. The associations of patient
characteristics with treatment responsiveness were investigated. SUBJECTS AND
METHODS: Four sessions of bifrontal tDCS (F4: anode, F3: cathode) and TMNMT were
conducted over a 2-week period in tinnitus patients. For tDCS, the stimulation
intensity was 1.5 mA and the duration was approximately 20 min. During tDCS,
patients listened to music lacking the frequency band within 1 octave of the
tinnitus frequency. Patients were also instructed to listen to this music at home
for at least 2 hours per day. One month after the final tDCS session, loudness
(LD), awareness (AW), annoyance (AN), and effect on life (EL) of tinnitus were
assessed subjectively using a visual analog scale. RESULTS: A total of 14
patients were enrolled in this study. After treatment, a 50% or greater
improvement in AN, AW, EL, and LD was observed in 57.1, 42.9, 35.7, and 28.6% of
patients, respectively. Furthermore, 78.6% of patients showed a 50% or greater
improvement in their tinnitus handicap inventory scores. For AN, the absence of
sleep disturbance was significantly associated with treatment responsiveness
(p=0.041, OR=24.0). CONCLUSIONS: Combined bifrontal tDCS and TMNMT is a promising
treatment for chronic tinnitus. To maximize the treatment outcomes of this
therapy, sleep disturbances should also be addressed in candidate patients.
PMID- 28417105
TI - Substitution Patterns of Phoneme Errors in Hearing Aid and Cochlear Implant
Users.
AB - BACKGROUND AND OBJECTIVES: It is acknowledged that speech perceptual errors are
increased in listeners who have sensorineural hearing loss as noise increases.
However, there is a lack of detailed information for their error pattern. The
purpose of the present study was to analyze substitution patterns of phoneme
errors in Korean hearing aid (HA) and cochlear implant (CI) users who are
postlingually deafened adults. SUBJECTS AND METHODS: In quiet and under two noise
conditions, the phoneme errors of twenty HA and fourteen CI users were measured
by using monosyllabic words, and a substitution pattern was analyzed in terms of
manner of articulation. RESULTS: The results showed that both groups had a high
percentage of nasal and plosive substitutions regardless of background
conditions. CONCLUSIONS: This finding will provide vital information for
understanding the speech perception of hearing-impaired listeners and for
improving their ability to communicate when applied to auditory training.
PMID- 28417106
TI - Comparative Analysis of the Combined Therapeutic Effects of Lipoprostaglandin E1
on Sudden Idiopathic Sensorineural Hearing Loss.
AB - BACKGROUND AND OBJECTIVES: Viral and vascular disorders are considered to be a
major cause of idiopathic sudden sensorineural hearing loss (ISSNHL).
Lipoprostaglandin E1 (lipo-PGE1) has vasodilating activity and has been used to
treat ISSNHL. The purpose of this study was to determine the specific therapeutic
effects of lipo-PGE1 and compare them to other treatment modalities for ISSNHL.
SUBJECTS AND METHODS: The study group had 1,052 patients diagnosed with ISSNHL.
All were treated with steroid, carbogen inhalation, stellate ganglion block
(SGB), or PGE1. The CP group (steroid, carbogen inhalation, and PGE1 injection;
288 patients) was treated with lipo-PGE1 and carbogen inhalation, the CS group
(steroid, carbogen inhalation, and stellate ganglion block; 232 patients) with
steroid, carbogen inhalation, and SGB, the C group (steroid and carbogen
inhalation; 284 patients) with steroid and carbogen, and the control group
(steroid only; 248 patients) with steroid only. Patients in the groups receiving
lipo-PGE1 received a continuous infusion of 10 uL lipo-PGE1. RESULTS: The overall
recovery rate after treatment was 52.2%, and recovery rates by group were 67.7%
in the CP group, 54.3% in the CS group, 52.1% in the C group, and 32.2% in the
control group. Therefore, the therapeutic results in groups treated with lipo
PGE1 were better than results in other groups. The difference was statistically
significant. CONCLUSIONS: The study results suggested that the CP group received
effective treatment modalities for ISSNHL. The combined therapy of lipo-PGE1 with
carbogen inhalation in patients with ISSNHL was more beneficial than other
treatment modalities.
PMID- 28417107
TI - Analysis of Effect of Eggshell Membrane Patching for Moderate-to-Large Traumatic
Tympanic Membrane Perforation.
AB - BACKGROUND AND OBJECTIVES: To evaluate the effect of eggshell membrane (ESM)
patching for tympanic membrane (TM) perforation, and to investigate correlations
between healing time and age, gender, patching time, perforation size, and
perforation location. SUBJECTS AND METHODS: One hundred and seventy-five patients
diagnosed with traumatic TM perforation at the Department of Otorhinolaryngology
Head and Neck Surgery, Korea University Ansan Hospital, between January 2008 and
October 2013. Patients were divided into two groups, according to perforation
edge approximation or ESM patching treatment. Healing time was compared between
the group that received perforation edge approximation and the group that
received ESM patching. Perforation grade, age, onset, and location were also
compared between the two groups. RESULTS: ESM patching significantly improved
healing time compared to spontaneous healing, especially in patients with
moderate or large traumatic TM perforations (>=grade II). However, patient age,
gender, perforation location, and especially timing of procedure, did not
significantly affect healing time. CONCLUSIONS: ESM patching can be a good
treatment choice to promote tympanic membrane healing in large traumatic TM
perforations.
PMID- 28417108
TI - Factors Prognostic of Season-Associated Sudden Sensorineural Hearing Loss: A
Retrospective Observational Study.
AB - BACKGROUND AND OBJECTIVES: This study examined whether the prognosis of sudden
deafness was dependent on the time of onset and evaluated the factors affecting
prognosis during each period. SUBJECTS AND METHODS: Patients who developed sudden
hearing loss from January 2005 to December 2015 were evaluated retrospectively.
Meteorological data were obtained from the official website of the Korea
Meteorological Administration. Factors prognostic of hearing recovery rate were
analyzed. RESULTS: The hearing recovery rate of the 318 patients who developed
sudden deafness did not differ significantly by month. Mean temperature and daily
temperature range at onset of sudden deafness were not associated with recovery
rate. CONCLUSIONS: The recovery rate in patients with sudden deafness did not
differ markedly by season.
PMID- 28417109
TI - Intractable Methicillin-Resistant Staphylococcus Aureus Otorrhea with Silicone
Impression in the Middle Ear.
AB - We report a case of methicillin-resistant Staphylococcus aureus (MRSA) otorrhea
with impression material of hearing aid in the middle ear. The patient had
chronic otitis media in the right ear with sensorineural hearing loss in both
ears. The silicone flowed into the middle ear through a tympanic membrane
perforation during the process of making an ear mold. Several days after hearing
aid fitting, the patient had severe otalgia, intractable otorrhea, aggravated
hearing loss, and dizziness. The pus culture and sensitivity test revealed MRSA.
After topical treatment using diluted vinegar irrigation and ototopical
vancomycin solution, intractable otorrhea was controlled. The infected silicone
impression was removed by canal wall-up mastoidectomy, and hearing was saved. We
present here a review of the literature regarding silicone impression in the
middle ear after hearing aid mold fitting.
PMID- 28417110
TI - Kawasaki Disease and Labyrinthitis: An Underdiagnosed Complication.
AB - Sensorineural hearing loss (SNHL) that is seldom cited as a Kawasaki disease (KD)
complication is known as an additional, potentially severe, and frequently
irreversible sequel. Furthermore the vestibular functions of KD have been
underestimated and it could be an important complication combined with SNHL in
KD. We described a case that a 4 year-old boy who developed vestibular loss with
SNHL has recovered successfully with a combined treatment.
PMID- 28417111
TI - Speech Intelligibility in Persian Hearing Impaired Children with Cochlear
Implants and Hearing Aids.
AB - The aim of present study is to evaluate and compare speech intelligibility in
hearing impaired children with cochlear implants (CI) and hearing aid (HA) users
and children with normal hearing (NH). The sample consisted of 45 Persian
speaking children aged 3 to 5-years-old. They were divided into three groups, and
each group had 15, children, children with CI and children using hearing aids in
Hamadan. Participants was evaluated by the test of speech intelligibility level.
Results of ANOVA on speech intelligibility test showed that NH children had
significantly better reading performance than hearing impaired children with CI
and HA. Post-hoc analysis, using Scheffe test, indicated that the mean score of
speech intelligibility of normal children was higher than the HA and CI groups;
but the difference was not significant between mean of speech intelligibility in
children with hearing loss that use cochlear implant and those using HA. It is
clear that even with remarkabkle advances in HA technology, many hearing impaired
children continue to find speech production a challenging problem. Given that
speech intelligibility is a key element in proper communication and social
interaction, consequently, educational and rehabilitation programs are essential
to improve speech intelligibility of children with hearing loss.
PMID- 28417114
TI - Polymorphs of two dimensional phosphorus and arsenic: insight from an
evolutionary search.
AB - Using an evolutionary algorithm, in conjunction with density functional theory
(DFT) based electronic, ionic and cell relaxation, we perform an extensive search
for the crystal structures of possible two dimensional (2D) allotropes of
phosphorus and arsenic. In addition to previously reported allotropes like alpha,
beta, gamma and delta, we discover four new allotropes, whose cohesive energies
differ from that of the ground state (alpha and beta, in the case of P and As,
respectively) by merely ~2-10 meV per atom. In terms of electrical properties,
all of them are semiconductors, although the magnitude and nature of the bandgap
(direct/indirect) vary considerably. We explain the diversity in terms of the
atomic character of the valence and conduction bands of the allotropes. Barring a
few exceptions, we find that the effective mass of both the electron and hole has
marked anisotropies for most of the allotropes.
PMID- 28417113
TI - Temporal Registration in In-Utero Volumetric MRI Time Series.
AB - We present a robust method to correct for motion and deformations in in-utero
volumetric MRI time series. Spatio-temporal analysis of dynamic MRI requires
robust alignment across time in the presence of substantial and unpredictable
motion. We make a Markov assumption on the nature of deformations to take
advantage of the temporal structure in the image data. Forward message passing in
the corresponding hidden Markov model (HMM) yields an estimation algorithm that
only has to account for relatively small motion between consecutive frames. We
demonstrate the utility of the temporal model by showing that its use improves
the accuracy of the segmentation propagation through temporal registration. Our
results suggest that the proposed model captures accurately the temporal dynamics
of deformations in in-utero MRI time series.
PMID- 28417112
TI - Lectin-type oxidized LDL receptor-1 distinguishes population of human
polymorphonuclear myeloid-derived suppressor cells in cancer patients.
AB - Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important
regulators of immune responses in cancer and have been directly implicated in
promotion of tumor progression. However, the heterogeneity of these cells and
lack of distinct markers hampers the progress in understanding of the biology and
clinical importance of these cells. Using partial enrichment of PMN-MDSC with
gradient centrifugation we determined that low density PMN-MDSC and high density
neutrophils from the same cancer patients had a distinct gene profile. Most
prominent changes were observed in the expression of genes associated with
endoplasmic reticulum (ER) stress. Surprisingly, low-density lipoprotein (LDL)
was one of the most increased regulators and its receptor oxidized LDL receptor 1
OLR1 was one of the most overexpressed genes in PMN-MDSC. Lectin-type oxidized
LDL receptor 1 (LOX-1) encoded by OLR1 was practically undetectable in
neutrophils in peripheral blood of healthy donors, whereas 5-15% of total
neutrophils in cancer patients and 15-50% of neutrophils in tumor tissues were
LOX-1+. In contrast to their LOX-1- counterparts, LOX-1+ neutrophils had gene
signature, potent immune suppressive activity, up-regulation of ER stress, and
other biochemical characteristics of PMN-MDSC. Moreover, induction of ER stress
in neutrophils from healthy donors up-regulated LOX-1 expression and converted
these cells to suppressive PMN-MDSC. Thus, we identified a specific marker of
human PMN-MDSC associated with ER stress and lipid metabolism, which provides new
insight to the biology and potential therapeutic targeting of these cells.
PMID- 28417115
TI - Synthesis of calcium carbonate in trace water environments.
AB - Calcium carbonate (CaCO3) was synthesized from diverse water-free alcohol
solutions, resulting in the formation of vaterite and calcite precipitates, or
stable particle suspensions, with the dimensions and morphologies depending upon
the conditions used. The obtained results shed light on the importance of
solvation during crystallization of CaCO3 and open a novel synthetic route for
its precipitation in organic solvents.
PMID- 28417116
TI - A long persistence phosphor tailored quasi-solid-state dye-sensitized solar cell
that generates electricity in sunny and dark weathers.
AB - An all-weather quasi-solid-state dye-sensitized solar cell is built using a long
persistence phosphor tailored mesoscopic TiO2 photoanode and a three-dimensional
conducting polymer gel electrolyte. The so-called all-weather solar cell yields a
maximum efficiency of 28.7% in the dark, making a promising photovoltaic
revolutionary for state-of-the-art photovoltaics.
PMID- 28417117
TI - Poly(naphthalene diimide) vinylene: solid state red emission and semiconducting
properties for transistors.
AB - In this work, a conjugated polymer PNV is developed, linking naphthalene diimide
with a vinyl linkage. Owing to the C-HO hydrogen bond between the carbonyl and
the vinyl, PNV exhibits a high red emission with a quantum yield of 33.4% in the
solid state while it shows n-type properties with an electron mobility up to 1.5
* 10-3 cm2 V-1 s-1 in organic field effect transistors, simultaneously.
PMID- 28417118
TI - A very simple method for the preparation of Au/TiO2 plasmonic photocatalysts
working under irradiation of visible light in the range of 600-700 nm.
AB - By using a facile calcination method, we succeeded in the preparation of
partially spherical gold particles supported on TiO2 exhibiting photoabsorption
due to surface plasmon resonance at around 620 nm. Surprisingly, the selective
oxidation of benzyl alcohol to benzaldehyde occurred in an aqueous suspension of
thus-prepared Au/TiO2 under irradiation of light from a Xe lamp with an R60 cut
off filter (lambda > 600 nm), and the apparent quantum efficiency reached 7.2% at
625 nm and 4.2% even at 700 nm.
PMID- 28417119
TI - Dehydrogenative cross-coupling of o-carborane with thiophenes via Ir-catalyzed
regioselective cage B-H and C(sp2)-H activation.
AB - Ir-Catalyzed -COOH directed site-selective B-H/C-H dehydrogenative cross-coupling
of o-carborane with thiophenes has been achieved for the first time. Without any
pre-functionalization, carboranyl carboxylic acids and thiophenes can serve as
suitable coupling partners, resulting in the preparation of 4-thienyl-o
carboranes in a simple one-pot process for potential applications in materials.
PMID- 28417120
TI - Enhanced CO2 uptake by intramolecular proton transfer reactions in amino
functionalized pyridine-based ILs.
AB - This work presents a new strategy for the promotion of CO2 uptake by an
intramolecular proton transfer reaction in amino functionalized hydroxypyridine
based anions.
PMID- 28417122
TI - Frequency-control of protein translocation across an oscillating nanopore.
AB - The translocation of a lipid binding protein (LBP) is studied using a
phenomenological coarse-grained computational model that simplifies both chain
and pore geometry. We investigated via molecular dynamics the interplay between
transport and unfolding in the presence of a nanopore whose section oscillates
periodically in time with a frequency omega, a motion often referred to as the
radial breathing mode (RBM). We found that the LPB when mechanically pulled into
the vibrating nanopore exhibits a translocation dynamics that in some frequency
range is accelerated and shows a frequency locking to the pore dynamics. The main
effect of pore vibrations is the suppression of stalling events of the
translocation dynamics, hence, proper frequency tuning allows both regularization
and control of the overall transport process. Finally, the interpretation of the
simulation results is easily achieved by resorting to a first passage theory of
elementary driven-diffusion processes.
PMID- 28417123
TI - Design of anion-selective PET probes based on azacryptands: the effect of pH on
binding and fluorescence properties.
AB - Design of PET probes for anions working in an aqueous buffered solution is
described. The design has been used to develop selective fluorescent probes for
sulfate and pyrophosphate. The relationship between the selectivity of receptors
towards anions, their conformation, fluorescence response and the pH of the
solution has been studied in detail.
PMID- 28417124
TI - Revisiting the (E + A) ? (e + a) problems of polyatomic systems with trigonal
symmetry: general expansions of their vibronic Hamiltonians.
AB - In this work, we derive general expansions in vibrational coordinates for the (E
+ A) ? (e + a) vibronic Hamiltonians of molecules with one and only one C3 axis.
We first derive the expansion for the lowest C3 symmetry. Additional symmetry
elements systematically eliminate terms in the expansion. We compare our
expansions with the previous results for two cases, the and the C3 (E + A) ? e.
The first comparison demonstrates the robustness, completeness, conciseness, and
convenience of our formalism. There is a systematic discrepancy in the second
comparison. We discuss the origin of the discrepancy and use a numerical example
to corroborate our expansion. Our formalism covers 153 vibronic problems in 6
point groups. It also gives general expansions for the spin-orbit vibronic
Hamiltonians of the p-type (E + A) ? (e + a) problems.
PMID- 28417127
TI - On the formation of stripe, sigma, and honeycomb phases in a core-corona system.
AB - Using Monte Carlo simulations and free-energy calculations, we investigate the
phase behaviour of a two-dimensional core-corona system. We model this system as
particles consisting of an impenetrable hard core of diameter sigmaHD surrounded
by a purely repulsive soft corona of diameter delta = 1.95sigmaHD. At low
densities, we observe the spontaneous formation of a phase with a stripe texture
as well as a honeycomb-like phase driven by both energy and entropy
considerations. At high densities, we find that a two-dimensional analogue of the
periodic sigma phase, considered as an approximant of dodecagonal quasicrystals,
is energetically stabilised with respect to two distinct dodecagonal
quasicrystals, namely, a square-triangle tiling and a square-triangle-shield
tiling. We also find the formation of stable hexagonal phases at three distinct
density ranges, which are energetically driven, i.e. by minimising the overlap of
coronas. Furthermore, our calculations show that the low-density dodecagonal
quasicrystal that was previously reported by Dotera et al., [Nature, 2014, 506,
208] is kinetically formed in the coexistence region between the honeycomb and
the medium-density hexagonal phase.
PMID- 28417128
TI - Surface reactivity and vacancy defects in single-layer borophene polymorphs.
AB - Single-layer borophene is a novel 2D material which combines high strength, light
weight and metallicity. Using first-principles calculations, we systematically
investigate the defect formation and surface reactivity in three major borophene
polymorphs (alpha, beta and triangular). We find that beta-B is generally the
most reactive borophene form, while alpha-B is the least reactive. In particular,
there is more than 1.5 eV difference in substitutional energies for typical
dopants in beta-B and alpha-B polymorphs. Single vacancy defects can be created
quite easily in all borophene sheets with formation energies (0.16 to 1.93 eV)
much lower than those in graphene (7.69 eV). Adatom adsorption is exothermic and
stabilizes electron-deficient boron monolayers. Many interesting properties arise
from the rich structural chemistry of borophene, comprising four-, five-, and six
coordinated atoms, as well as hexagonal vacancies.
PMID- 28417130
TI - Iron isotopic composition of blood serum in anemia of chronic kidney disease.
AB - Chronic kidney disease (CKD) is a general term for disorders that affect the
structure and function of the kidneys. Iron deficiency (ID) and anemia occur in
the vast majority of CKD patients, most of whom are elderly. However,
establishing the cause of anemia in CKD, and therefore making an informed
decision concerning the corresponding therapeutic treatment, is still a
challenge. High-precision Fe isotopic analysis of blood serum samples of CKD
patients with and without ID/anemia was performed via multi-collector inductively
coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with
CKD and/or iron disorders showed a heavier serum Fe isotopic composition than
controls. Many clinical parameters used for the diagnosis and follow-up of anemia
correlated significantly with the serum Fe isotopic composition. In contrast, no
relation was observed between the serum Fe isotopic composition and the estimated
glomerular filtration rate as a measure of kidney function. Among the CKD
patients, the serum Fe isotopic composition was substantially heavier in the
occurrence of ID anemia, while erythropoietin-related anemia did not exert this
effect. The Fe isotopic composition can thus be useful for distinguishing these
different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin
related anemia.
PMID- 28417131
TI - Asthma in Singapore: Past, Present and Future.
PMID- 28417132
TI - Awareness and Attitudes of Community-Dwelling Individuals in Singapore towards
Participating in Advance Care Planning.
AB - INTRODUCTION: Advance care planning (ACP) is an important aspect of end-of-life
care that has been shown to improve patient autonomy in decision-making and
reduce stress for surviving family members. Given the rapidly ageing population
in Singapore, a greater emphasis on end-of-life care planning is needed. This
study therefore sought to examine the awareness and attitudes of the general
Singaporean community towards participating in ACP, which are not known hitherto.
MATERIALS AND METHODS: A 24-item interviewer-administered questionnaire was
constructed and administered via door-to-door survey amongst community-dwelling
residents living in Housing and Development Board (HDB) flats across Singapore,
selected via a two-stage stratified random sampling. RESULTS: Of the 406
completed surveys, 14.4% of respondents had heard of ACP (n = 58), mostly through
the media (67.9%), from family and friends (21.4%) and healthcare providers
(21.4%). Only 26.8% of those who had previously heard of ACP knew how to begin an
ACP discussion and 12.5% of them had a prior ACP discussion. After education, the
majority of respondents were willing to begin an ACP discussion (n = 236, 60.1%).
Being of an older age, having a life threatening illness, and having more
knowledge about ACP were significant factors associated with willingness to have
an ACP discussion. Barriers included perceiving oneself as still healthy and
preferring the family to make decisions instead. CONCLUSION: There is a low
awareness but high expressed willingness to engage in an ACP discussion amongst
the Singaporean community. More efforts are needed to educate the public about
ACP, engage the family unit and correct the present misconceptions.
PMID- 28417133
TI - Comorbid Diabetes and Depression among Older Adults - Prevalence, Correlates,
Disability and Healthcare Utilisation.
AB - INTRODUCTION: The objectives of this current study were to: 1) examine the
prevalence and correlates of diabetes mellitus (DM) among older adults (aged 60
years and above) in a multi-ethnic population; 2) examine the prevalence and
correlates of comorbid DM and depression among them; and 3) assess the effect of
comorbid depression on disability, cognition and healthcare utilisation.
MATERIALS AND METHODS: Data for the current study came from the Well-being of the
Singapore Elderly (WiSE) study; a single phase, cross-sectional survey conducted
among Singapore residents aged 60 years and above. A total of 2565 respondents
completed the survey; depression was assessed using the Automated Geriatric
Examination for Computer Assisted Taxonomy (AGECAT) while a diagnosis of DM was
considered if respondents stated that a doctor had diagnosed them with DM.
RESULTS: DM was reported by 25.5% of the population. The prevalence of depression
was significantly higher in those diagnosed with DM than those without DM (6% vs
3%). After adjusting for sociodemographic correlates, smoking and other chronic
conditions, DM remained significantly associated with depression and subsyndromal
depression. However, after including measures of functioning and cognitive
impairment as covariates, DM was not significantly related to depression and
subsyndromal depression. Those with comorbid DM and depression were more likely
to be of Indian and Malay ethnicity, aged 75 to 84 years (versus 60 to 74 years)
and widowed. CONCLUSION: Given the significant association of certain
sociodemographic groups with comorbid depression among those with DM, targeted
interventions for prevention and early diagnosis in these groups should be
considered.
PMID- 28417134
TI - Predictors and Moderators of Post-traumatic Stress Disorder: An Investigation of
Anxiety Sensitivity and Resilience in Individuals with Chronic Pain.
AB - INTRODUCTION: Anxiety sensitivity has been proposed as a psychological
vulnerability factor for post-traumatic stress disorder (PTSD). Studies have also
supported the protective role of resilience for overcoming the negative effects
of trauma exposure. Given the linkages between anxiety sensitivity, resilience,
trauma exposure and post-traumatic stress, this study explored the potential
moderating roles of anxiety sensitivity and resilience on the association between
trauma history and PTSD symptoms in a sample of individuals with chronic pain.
MATERIALS AND METHODS: A total of 100 patients with chronic pain were recruited
from a large public hospital. Patients who had pain lasting for more than 3
months and a pain intensity rating of at least 4/10 were included. The study
participants were administered measures of PTSD symptoms (PTSD Checklist -
Civilian Version), resilience (Brief Resilient Coping Scale) and anxiety
sensitivity (Anxiety Sensitivity Index). RESULTS: An analysis of outcome measures
indicated that anxiety sensitivity and resilience were independently associated
with PTSD symptoms, where betas were 0.57 and -0.23, respectively. The
relationship between trauma and PTSD symptom severity was also moderated by
anxiety sensitivity. Trauma history was associated with higher PTSD symptom
severity only in those with high anxiety sensitivity. However, contrary to the
hypotheses, resilience did not serve as a moderator. CONCLUSION: There are
potential benefits of PTSD interventions that increase resilience and decrease
anxiety sensitivity in individuals with chronic pain, especially for those who
have experienced a traumatic event. Given that the presence of PTSD
symptomatology in chronic pain populations negatively impact patient well-being,
it would be important for clinicians to assess, monitor and treat PTSD in
individuals with chronic pain.
PMID- 28417135
TI - A Training Model for Introducing a Novel Surgical Procedure into Clinical
Practice: Our Experience on Peroral Endoscopic Myotomy for Achalasia.
PMID- 28417136
TI - Too Old for Surgery? Outcomes of Hip Fracture Surgery in Centenarians.
PMID- 28417137
TI - Adult Onset Sporadic Cerebellar Ataxia in Singapore: Diagnostic Outcomes of
Paraneoplastic Antibody Testing and Early Clinical Features of Paraneoplastic
Cerebellar Degeneration.
PMID- 28417139
TI - The Fragility Index: a P-value in sheep's clothing?
PMID- 28417138
TI - Long-term exposure to ambient air pollution and traffic noise and incident
hypertension in seven cohorts of the European study of cohorts for air pollution
effects (ESCAPE).
AB - Aims: We investigated whether traffic-related air pollution and noise are
associated with incident hypertension in European cohorts. Methods and results:
We included seven cohorts of the European study of cohorts for air pollution
effects (ESCAPE). We modelled concentrations of particulate matter with
aerodynamic diameter <=2.5 um (PM2.5), <=10 um (PM10), >2.5, and <=10 um
(PMcoarse), soot (PM2.5 absorbance), and nitrogen oxides at the addresses of
participants with land use regression. Residential exposure to traffic noise was
modelled at the facade according to the EU Directive 2002/49/EC. We assessed
hypertension as (i) self-reported and (ii) measured (systolic BP >= 140 mmHg or
diastolic BP >= 90 mmHg or intake of BP lowering medication (BPLM). We used
Poisson regression with robust variance estimation to analyse associations of
traffic-related exposures with incidence of hypertension, controlling for
relevant confounders, and combined the results from individual studies with
random-effects meta-analysis. Among 41 072 participants free of self-reported
hypertension at baseline, 6207 (15.1%) incident cases occurred within 5-9 years
of follow-up. Incidence of self-reported hypertension was positively associated
with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI):1.08; 1.37] per
5 ug/m3) and PM2.5 absorbance (RR 1.13 [95% CI:1.02; 1.24] per 10 - 5m - 1).
These estimates decreased slightly upon adjustment for road traffic noise. Road
traffic noise was weakly positively associated with the incidence of self
reported hypertension. Among 10 896 participants at risk, 3549 new cases of
measured hypertension occurred. We found no clear associations with measured
hypertension. Conclusion: Long-term residential exposures to air pollution and
noise are associated with increased incidence of self-reported hypertension.
PMID- 28417140
TI - Onychomycosis Due to Arthrinium arundinis: A Case Report.
PMID- 28417141
TI - Incidence and Prevalence of Psoriasis in Denmark.
AB - The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012
were examined. There was a female predominance ranging between 50.0% (2007) and
55.4% (2009), and the mean age at time of diagnosis was 47.7-58.7 years. A total
of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence
rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak
incidence of 199.5 in 2010. Incidence rates were higher for women, and patients
aged 60-69 years, respectively. Use of systemic non-biologic agents, i.e.
methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA)
increased over the study course, and were used in 15.0% of all patients. Biologic
agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were
utilized in 2.7% of patients. On a national level, incidence of psoriasis
fluctuated during the 10-year study course. The relationship between psoriasis
incidence and age appeared to be relatively linear, and disease prevalence was
comparable to that in other European countries.
PMID- 28417142
TI - Heterozygous PDGFRB Mutation in a Three-generation Family with Autosomal Dominant
Infantile Myofibromatosis.
PMID- 28417143
TI - Impact of High Age and Comorbidity on Management Decisions and Adherence to
Guidelines in Patients with Keratinocyte Skin Cancer.
AB - Appropriate medical decision-making in patients with keratinocyte skin cancer
(KSC) can be challenging, especially in those with a limited life expectancy
(LEx). Treatment should be beneficial for the individual patient, the risk of
both over- and under-treatment should be carefully considered, and deviation from
guideline recommendations may be necessary. In this study retrospective analysis
was performed to determine the influence of age and comorbidity, both factors
strongly related to limited LEx, on KSC management in daily practice. After
analysis of 401 patients it was found that management in patients with KSC is not
influenced, or is only minimally influenced, by high age and comorbidity. Better
integration of aspects related to a limited LEx in KSC management might optimize
care and prevent overtreatment. Future research on the general prognostication,
prediction of the patient burden caused by tumour and treatment, and time-to
benefit in KSC management is strongly recommended.
PMID- 28417144
TI - The effect of reconstruction works on planktonic bacterial diversity of a unique
thermal lake revealed by cultivation, molecular cloning and next generation
sequencing.
AB - The aim of this study was to gain detailed information about the diversity of
planktonic bacterial communities of a worldwide special peat bedded natural
thermal spa lake, and to reveal the effect of a lake wall reconstruction work. To
compare the efficiency of different methods used for analyzing bacterial
diversity, cultivation, molecular cloning and pyrosequencing were applied
simultaneously. Despite the almost unchanged physical-chemical parameters and
cell count values of lake water, remarkable differences were observed in the
planktonic bacterial community structures during and after the reconstruction by
all applied microbiological approaches. Rhodobacter sp. was found to be one of
the most abundant community members during the works probably due to the sediment
stirring effect of the reconstruction. Following the reconstruction higher
diversity was detected than during the works by all approaches. Bacterial strains
related to species Chryseobacterium and Exiguobacterium, furthermore sequences
related to Arcobacter, Gemmobacter and MWH-UniP1 aquatic group were identified in
the highest proportion at that time. Although the differences revealed by
cultivation based and independent community structures were significant, only
minor disparities were found by molecular cloning and next generation sequencing
techniques.
PMID- 28417145
TI - Relationship in Pacemaker Neurons Between the Long-Term Correlations of Membrane
Voltage Fluctuations and the Corresponding Duration of the Inter-Spike Interval.
AB - Several studies of the behavior in the voltage and frequency fluctuations of the
neural electrical activity have been performed. Here, we explored the particular
association between behavior of the voltage fluctuations in the inter-spike
segment (VFIS) and the inter-spike intervals (ISI) of F1 pacemaker neurons from
H. aspersa, by disturbing the intracellular calcium handling with cadmium and
caffeine. The scaling exponent alpha of the VFIS, as provided by detrended
fluctuations analysis, in conjunction with the corresponding duration of ISI to
estimate the determination coefficient R 2 (48-50 intervals per neuron, N = 5)
were all evaluated. The time-varying scaling exponent alpha(t) of VFIS was also
studied (20 segments per neuron, N = 11). The R 2 obtained in control conditions
was 0.683 ([0.647 0.776] lower and upper quartiles), 0.405 [0.381 0.495] by using
cadmium, and 0.151 [0.118 0.222] with caffeine (P < 0.05). A non-uniform scaling
exponent alpha(t) showing a profile throughout the duration of the VFIS was
further identified. A significant reduction of long-term correlations by cadmium
was confirmed in the first part of this profile (P = 0.0001), but no significant
reductions were detected by using caffeine. Our findings endorse that the
behavior of the VFIS appears associated to the activation of different
populations of ionic channels, which establish the neural membrane potential and
are mediated by the intracellular calcium handling. Thus, we provide evidence to
consider that the behavior of the VFIS, as determined by the scaling exponent
alpha, conveys insights into mechanisms regulating the excitability of pacemaker
neurons.
PMID- 28417147
TI - Cortical Histomorphometry of the Human Humerus During Ontogeny.
AB - Modeling and remodeling are two key determinants of human skeletal growth though
little is known about the histomorphometry of cortical bone during ontogeny. In
this study, we examined the density and geometric properties of primary and
secondary osteons (osteon area and diameter, vascular canal area and diameter) in
subperiosteal cortical bone from the human humerus (n = 84) between birth and age
18 years. Sections were removed from the anterior midshaft aspect of humeri from
skeletons. Age-at-death was reconstructed using standard osteological techniques.
Analyses revealed significant correlation between the histomorphometric variables
and age. Higher densities of primary osteons occurred between infancy and 7 years
of age but were almost completely replaced by secondary osteons after 14 years of
age. The geometry of primary osteons was less clearly related to age. Secondary
osteons were visible after 2 years of age and reached their greatest densities in
the oldest individuals. Osteon size was positively but weakly influenced by age.
Our data imply that modeling and remodeling are age-dependent processes that vary
markedly from birth to adulthood in the human humerus.
PMID- 28417146
TI - Repeated mild traumatic brain injury in female rats increases lipid peroxidation
in neurons.
AB - Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by
repeated insult. Animal models of repeated closed-head mTBI provide the
opportunity to define acute pathological mechanisms as the number of mTBI
increases. Furthermore, little is known about the effects of mTBI impact site,
and how this may affect brain function. We use a closed head, weight drop model
of mTBI that allows head movement following impact, in adult female rats to
determine the role of the number and location of mTBI on brain pathology and
behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact
sites were used, anterior (bregma) and posterior (lambda). Location of the impact
had no significant effect on impact forces (450 N), and the weight impact
locations were on average 5.4 mm from the desired impact site. No between
location vertical linear head kinematic differences were observed immediately
following impact, however, in the 300 ms post-impact, significantly higher mean
vertical head displacement and velocity were observed in the mTBI lambda trials.
Breaches of the blood brain barrier were observed with three mTBI over bregma,
associated with immunohistochemical indicators of damage. However, an increased
incidence of hairline fractures of the skull and macroscopic haemorrhaging made
bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over
lambda did not cause skull fractures and were examined more comprehensively, with
outcomes following one, two or three mTBI or sham, delivered at 1 day intervals,
assessed on days 1-4. We observe a mild behavioural phenotype, with subtle
deficits in cognitive function, associated with no identifiable neuroanatomical
or inflammatory changes. However, an increase in lipid peroxidation in a subset
of cortical neurons following two mTBI indicates increasing oxidative damage with
repeated injury in female rats, supported by increased amyloid precursor protein
immunoreactivity with three mTBI. This study of acute events following closed
head mTBI identifies lipid peroxidation in neurons at the same time as cognitive
deficits. Our study adds to existing literature, providing biomechanics data and
demonstrating mild cognitive disturbances associated with diffuse injury,
predominantly to grey matter, acutely following repeated mTBI.
PMID- 28417148
TI - Relationship Between Nutritional Factors and Hip Bone Density in Individuals with
Chronic Stroke.
AB - The aim of this study was to investigate the relationship between dietary habits
and hip bone health in community-dwelling individuals with chronic stroke. The
usual dietary intake of 94 individuals with chronic stroke (30 women, mean age:
59.0 years) was assessed by a 3-day food record within a single week. Dual-energy
X-ray absorptiometry was used to measure bone mineral density (BMD) at both hips.
The results showed that low hip bone mass was found in 59 and 50 of the
participants on the affected and unaffected side, respectively. The mean hip BMD
was also significantly lower on the affected side than the unaffected side (P <
0.001). The intake of total fat, carbohydrates, calcium, magnesium, iron, zinc,
fiber, folic acid, vitamin B1, B2, B3, B6, C, and K was significantly lower than
the respective recommended daily intake values (P < 0.05). Multiple regression
analyses revealed that after adjusting for the effects of age, sex, body mass
index, post-stroke duration, side of paresis, motor impairment, physical activity
level, walking endurance, total calories intake, and total number of medications,
intake of protein, fiber, and magnesium remained significantly associated with
hip T score on the affected side, accounting for 4.2, 4.4, and 3.2% of the
variance, respectively. On the other hand, intake of protein and fiber was
independently associated with hip T score on the unaffected side, explaining 2.7
and 5.2% of the variance, respectively. The results highlighted the potential
relevance of diet modification in maintaining bone health post stroke, which
would require further study.
PMID- 28417149
TI - Clincal interpretation of the anti-tuberculosis drug concentrations in diabetic
and non-diabetic tuberculosis patients.
PMID- 28417150
TI - Torpor patterns in common hamsters with and without access to food stores.
AB - Hibernating species significantly reduce energy expenditure during winter by
entering torpor. Nevertheless, the various benefits of hibernation might be
counteracted by negative effects of torpor such as immune depression, oxidative
stress, or neuronal impairment. Considering these trade-offs, adequate energy
reserves could allow animals to reduce the time spent in torpor or the extent of
metabolic depression. Common hamsters use food stores during hibernation and
previously documented high individual variations in body temperature patterns
during winter could, therefore, be related to differences in external energy
reserves. In this study, we manipulated the availability of food stores under
laboratory conditions to investigate potential effects on hibernation patterns.
Female hamsters were kept in artificial burrows in climate chambers and
subcutaneous temperature was recorded using implanted data loggers. One group had
access to large food stores, whereas another group received daily food portions
which were removed on the next day if not consumed. Almost all hamsters without
access to food stores hibernated, while less than half of the individuals with
food stores entered deep torpor. Individuals without food hoards additionally
expressed more short torpor bouts and exhibited lower minimum subcutaneous
temperatures during torpor than those with food stores. Thus, individuals
confronted with lacking food reserves were more likely to hibernate and
additionally saved energy by entering short torpor bouts more frequently and
remaining at lower subcutaneous temperature both during torpor and euthermic
periods. In conclusion, our results demonstrate that food store availability
affects torpor expression and also highlight variation in torpor patterns and
energy-saving strategies in common hamsters.
PMID- 28417151
TI - A review of the role and clinical utility of anti-Ro52/TRIM21 in systemic
autoimmunity.
AB - Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found
in a number of systemic autoimmune conditions including Sjogren's syndrome,
systemic lupus erythematosus and systemic sclerosis, appearing in about half of
these patients. Once coupled with its closely related antibody, anti-Ro60 as the
anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct
pathogenic disease involvement and distinct clinical properties. As a result,
recent attention has turned to this antibody and its clinical associations and
utility. There is a suggestion of anti-Ro52 being associated with more clinical
and laboratory markers of disease; however, marked disagreements occur about its
association with various clinical entities such as interstitial lung disease and
Raynaud's phenomena. Nevertheless, with a relative paucity of studies about these
across the systemic autoimmunity paradigm, limited confidence can be invested in
these conclusions. Although the antibody holds great potential as a biomarker,
further studies examining its clinical utility are needed. This paper will review
the mechanisms of Ro52 as an autoantigen and the clinical associations of anti
Ro52 in human autoimmunity.
PMID- 28417152
TI - Review of surgical and anesthetic management for esophageal atresia with
tracheoesophageal fistula, unilateral pulmonary agenesis and dextrocardia.
AB - Association of unilateral severe pulmonary atresia or agenesis and esophageal
atresia (EA) with or without tracheoesophageal fistula (TEF) and dextrocardia is
a rare and highly lethal combination. We report a case of a full-term female
infant who had EA with TEF, right lung agenesis, and dextrocardia. Repair of the
fistula took place on day of life 3. We describe anesthetic and surgical concerns
of this patient's case which are keys to a good operative outcome as well as
follow-up for the patient.
PMID- 28417153
TI - Laparoscopic sacrocolpopexy compared with open abdominal sacrocolpopexy for vault
prolapse repair: a randomised controlled trial.
AB - INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the functional outcome
after laparoscopic sacrocolpopexy versus open sacrocolpopexy in women with vault
prolapse. METHODS: A multicentre randomised controlled trial was carried out at
four teaching and two university hospitals in the Netherlands in women with
symptomatic vault prolapse requiring surgical treatment. Participants were
randomised for laparoscopic or open sacrocolpopexy. Primary outcome was disease
specific quality of life measured using the Urinary Distress Inventory (UDI)
questionnaire at 12 months' follow-up. Secondary outcomes included anatomical
outcome and perioperative data. We needed 74 participants to show a difference of
10 points on the prolapse domain of the UDI 12 months after surgery (power of
80%, alpha error 0.05). RESULTS: Between 2007 and 2012, a total of 74 women were
randomised. Follow-up after 12 months showed no significant differences in domain
scores of the UDI between the two groups. After 12 months, both groups reported a
UDI score of 0.0 (IQR: 0-0) for the domain "genital prolapse", which was the
primary outcome. There were no significant differences between the two groups (p
= 0.93). The number of severe complications was 4 in the laparoscopic group
versus 7 in the open abdominal group (RR 0.57; 95% CI 0.50-2.27). There was less
blood loss and a shorter hospital stay after laparoscopy; 2 (IQR 2-3) versus 4
(IQR 3-5) days, which was statistically different. There was no significant
difference in anatomical outcome at 12 months. CONCLUSION: Our trial provides
evidence to support a laparoscopic approach when performing sacrocolpopexy, as
there was less blood loss and hospital stay was shorter, whereas functional and
anatomical outcome were not statistically different.
PMID- 28417154
TI - Bulkamid (PAHG) in mixed urinary incontinence: What is the outcome?
AB - INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI), defined as mixed
symptoms of stress urinary incontinence (SUI) and overactive bladder (OAB), is a
difficult entity if conservative treatment has failed. Cure rates are low
compared with SUI, particularly the OAB component, may deteriorate after sling
insertion. Bulking agents pose an appealing alternative for the treatment of MUI.
They have shown beneficial effect in small case studies, but larger series are
lacking. The aim of this prospective study was an analysis of treatment efficacy
and safety profile of the bulking agent, Bulkamid, in female patients with MUI.
METHODS: One hundred fifty-four women with MUI symptoms (components of SUI/OAB
within the limits of 60-40% either way) received bulking therapy with
polyacrylamide hydrogel (Bulkamid). Patients were followed-up 3 months
postoperatively. Primary outcome was the domain Incontinence impact on the King's
Health Questionnaire (KHQ). Secondary outcomes were the other KHQ domains, visual
analog scale (VAS), and International Continence Society (ICS) standardized pad
weight test as objective measurement of incontinence. RESULTS: Statistically
significant improvements were found for all KHQ domains, pad weight test, and the
visual analog scale (VAS) before and after bulking. Overall complication rate was
13%. CONCLUSIONS: This study has shown improvement in MUI after bulking therapy
according to both subjective and objective outcomes. We can advocate bulking
therapy for treating MUI, as it is simple and safe and shows both objective and
subjective improvement and relief. Long-term results (up to 1 year) are awaited.
PMID- 28417155
TI - Pelvic floor symptoms and quality of life changes during first pregnancy: a
prospective cohort study.
AB - INTRODUCTION AND HYPOTHESIS: We describe pelvic floor function in nulliparous
pregnant women. MATERIALS AND METHODS: Nulliparous midwifery patients completed
the Incontinence Severity Index (ISI), Pelvic Floor Impact Questionnaire (PFIQ
7), Wexner Fecal Incontinence Scale (W), and answered questions about sexual
activity and perineal pain at baseline during the first (T1), second (T2), or
third trimester (T3) and repeated in late T3. They also underwent a Pelvic Organ
Prolapse Quantification (POP-Q) exam at their baseline visit. Data were compared
across trimesters. Analysis of variance (ANOVA) and logistic regression accounted
for repeated measures and was controlled for age and education. RESULTS: We
recruited 627 women. In T1, 124 women gave baseline data and completed
questionnaires; in T2, 403; and in early T3, 96 (496 repeated questionnaires in
later T3). Besides an increase in genital hiatus and perineal body (all adjusted
p < .05), physical exam measures did not differ between trimesters. As pregnancy
progressed, urinary incontinence (UI) (T1 = 33, T2 = 44, T3 = 69% women with ISI
>0, all comparisons p < .02) and Incontinence Impact Questionnaire (IIQ-7) scores
increased. Fecal incontinence (FI) increased (T1 = 8, T2 = 15, T3 = 16% from T2
to T3, p = .04); the Colorectal-Anal Impact Questionnaire (CRAIQ-7) scores did
not. Perineal pain increased (T1 = 17, T2 = 18 and T3 = 40%, all adjusted p <
.001), and sexual activity decreased (T1 = 94, T2 = 90, T3 = 77% sexually active,
T1 vs T3 and T2 vs T3, p < .001) as pregnancy progressed. CONCLUSIONS: During
pregnancy, women experience worsening UI, FI, and perineal pain. UI symptoms are
associated with a negative impact on quality of life (QoL). Sexual activity
decreased and POP-Q stage did not change.
PMID- 28417156
TI - Patient satisfaction after laparoscopic lateral suspension with mesh for pelvic
organ prolapse: outcome report of a continuous series of 417 patients.
AB - INTRODUCTION AND HYPOTHESIS: Sacropexy is considered the gold standard for the
treatment of pelvic organ prolapse (POP) although dissection of the promontory
may be challenging, particularly in obese women. Laparoscopic lateral suspension
with mesh (LLS) could be an alternative. METHODS: LLS provides lateral attachment
by fibrosis of a vesicovaginal mesh. Clinical evaluation was performed at 1 year
using the simplified POP quantification system (POP-Q). Primary outcomes were
objective and subjective cure at 1 year. After a mean of 7.2 years the rates of
reoperation and complications were assessed as secondary outcomes. Patient
satisfaction was evaluated by telephone interview using a ten-point-scale and the
PGI-I scale. Factors predicting satisfaction were determined by logistic
regression analysis. RESULTS: A total of 417 patients were treated between 2003
and 2011. At 1 year 78.4% of patients were asymptomatic and anatomic success
rates were 91.6% for the anterior compartment, 93.6% for the apical compartment
and 85.3% for the posterior compartment. The complication rate of Clavien-Dindo
grade III or higher was 2.2%. The mesh exposure rate was 4.3% and the reoperation
rate was 7.3%. Of the 417 patients, 214 participated in the telephone interview.
Over 85% rated their situation as improved and satisfaction was associated with
the absence of concomitant hysterectomy. CONCLUSIONS: LLS is a safe technique
with promising results in terms of a composite outcome, low complication rates
and high long-term patient satisfaction. However, a randomized controlled trial
is needed to establish the technique as an alternative to sacropexy in the
treatment of POP in obese and high morbidity patients.
PMID- 28417157
TI - Impact of cachexia on outcomes in aggressive lymphomas.
AB - Cancer cachexia is defined as a state of involuntary weight loss, attributed to
altered body composition with muscle mass loss and/or loss of adiposity.
Identifying the association between cancer cachexia and outcomes may pave the way
for novel agents that target the cancer cachexia process. Clinical parameters for
measurement of cancer cachexia are needed. We conducted a single-institution
retrospective analysis that included 86 NHL patients with the aim of identifying
an association between cancer cachexia and outcomes in aggressive lymphomas using
the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87
93, 15). Impact of cachexia factors on progression-free survival (PFS) and
overall survival (OS) were assessed using log-rank test and Cox proportional
hazards regression. Patients were dichotomized around the median CXI into "non
cachectic" (CXI >=49.8, n = 41) and "cachectic" (CXI <49.8, n = 40) groups.
Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR =
4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is
prognostic in aggressive lymphomas and implies that novel therapeutic strategies
directed at reversing cachexia may improve survival in this population.
PMID- 28417158
TI - Incidence and predictive factors of Internet addiction among Chinese secondary
school students in Hong Kong: a longitudinal study.
AB - PURPOSE: Internet use has global influences on all aspects of life and has become
a growing concern. Cross-sectional studies on Internet addiction (IA) have been
reported but causality is often unclear. More longitudinal studies are warranted.
METHODS: We investigated incidence and predictors of IA conversion among
secondary school students. A 12-month longitudinal study was conducted among Hong
Kong Chinese Secondary 1-4 students (N = 8286). Using the 26-item Chen Internet
Addiction Scale (CIAS; cut-off >63), non-IA cases were identified at baseline.
Conversion to IA during the follow-up period was detected, with incidence and
predictors derived using multi-level models. RESULTS: Prevalence of IA was 16.0%
at baseline and incidence of IA was 11.81 per 100 person-years (13.74 for males
and 9.78 for females). Risk background factors were male sex, higher school
forms, and living with only one parent, while protective background factors were
having a mother/father with university education. Adjusted for all background
factors, higher baseline CIAS score (ORa = 1.07), longer hours spent online for
entertainment and social communication (ORa = 1.92 and 1.63 respectively), and
Health Belief Model (HBM) constructs (except perceived severity of IA and
perceived self-efficacy to reduce use) were significant predictors of conversion
to IA (ORa = 1.07-1.45). CONCLUSIONS: Prevalence and incidence of IA conversion
were high and need attention. Interventions should take into account risk
predictors identified, such as those of the HBM, and time management skills
should be enhanced. Screening is warranted to identify those at high risk (e.g.
high CIAS score) and provide them with primary and secondary interventions.
PMID- 28417159
TI - Endangered Mangroves in Segara Anakan, Indonesia: Effective and Failed Problem
Solving Policy Advice.
AB - The success of scientific knowledge transfer depends on if the decision maker can
transform the scientific advice into a policy that can be accepted by all
involved actors. We use a science-policy interactions model called research
integration-utilization to observe the process of scientific knowledge transfer
in the case of endangered mangroves in Segara Anakan, Indonesia. Scientific
knowledge is produced within the scientific system (research), science-based
solutions to problems are practically utilized by political actors (utilization),
and important links between research and utilization must be made (integration).
We looked for empirical evidence to test hypotheses about the research
integration-utilization model based on document analysis and expert interviews.
Our study finds that the failures in knowledge transfer are caused by the
inappropriate use of scientific findings. The district government is expected by
presidential decree to only used scientifically sound recommendations as a
prerequisite for designing the regulation. However, the district government
prefers to implement their own solutions because they believe that they
understand the solutions better than the researcher. In the process of
integration, the researcher cannot be involved, since the selection of scientific
recommendations here fully depends on the interests of the district government as
the powerful ally.
PMID- 28417160
TI - Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin
releasing peptide receptor antagonist 68Ga-RM2: Preliminary results in patients
with negative or inconclusive [18F]Fluoroethylcholine-PET/CT.
AB - PURPOSE/BACKGROUND: [18F]fluoroethylcholine (18FECH) has been shown to be a
valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited
accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that
binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT
is a promising technique for staging and restaging of PCa. We explore the value
of GRPr-PET using the 68Ga-labeled GRPr antagonist RM2 in a selected population
of patients with biochemically recurrent PCa and a negative/inconclusive 18FECH
PET/CT. MATERIAL AND METHODS: In this retrospective study 16 men with biochemical
PCa relapse and negative (n = 14) or inconclusive (n = 2) 18FECH-PET/CT underwent
whole-body 68Ga-RM2-PET/CT. Mean time from 18FECH-PET/CT to 68Ga-RM2-PET/CT was
6.1 +/- 6.8 months. Primary therapies in these patients were radical
prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients
(87.5%) had already undergone salvage therapies because of biochemical relapse
prior to 68Ga-RM2-PET/CT imaging. Mean +/- SD PSA at 68Ga-RM2-PET/CT was 19.4 +/-
53.5 ng/ml (range 1.06-226.4 ng/ml). RESULTS: 68Ga-RM2-PET/CT showed at least one
region with focal pathological uptake in 10/16 patients (62.5%), being suggestive
of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n
= 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive 68Ga-RM2
scans were positively confirmed by surgical resection and histology of the
lesions (n = 2), by response to site-directed therapies (n = 2) or by further
imaging (n = 3). Patients with a positive 68Ga-RM2-scan showed a significantly
higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative
scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant
antihormonal therapy had no apparent impact on the detection of recurrent
disease. CONCLUSION: Even in this highly selected population of patients with
known biochemical recurrence but negative or inconclusive 18FECH-PET/CT, a 68Ga
RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases.
Thus, 68Ga-RM2-PET/CT deserves further investigation as a promising imaging
modality for imaging PCa recurrence.
PMID- 28417161
TI - IFT54 regulates IFT20 stability but is not essential for tubulin transport during
ciliogenesis.
AB - Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary
components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT
B complex and is also associated with cytoplasmic microtubules (MTs). Loss of
IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal
calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been
proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled
coil (CC) domain binds IFT20. However, the precise function of these domains in
vivo is not well understood. We showed that in Chlamydomonas, loss of IFT54
completely blocks ciliogenesis but does not affect spindle formation and proper
cell cycle progression, even though IFT54 interacts with mitotic MTs.
Interestingly, IFT54 lacking the CH domain allows proper flagellar assembly. The
CH domain is required for the association of IFT54 with the axoneme but not with
mitotic MTs, and also regulates the flagellar import of IFT54 but not IFT81 and
IFT46. The C-terminal CC domain is essential for IFT54 to bind IFT20, and for its
recruitment to the basal body and incorporation into IFT complexes. Complete loss
of IFT54 or the CC domain destabilizes IFT20. ift54 mutant cells expressing the
CC domain alone rescue the stability of IFT20 and form stunted flagella with
accumulation of both IFT-A component IFT43 and IFT-B component IFT46, indicating
that IFT54 also functions in IFT turn-around at the flagellar tip.
PMID- 28417162
TI - S100A6 protein: functional roles.
AB - S100A6 protein belongs to the A group of the S100 protein family of Ca2+-binding
proteins. It is expressed in a limited number of cell types in adult normal
tissues and in several tumor cell types. As an intracellular protein, S100A6 has
been implicated in the regulation of several cellular functions, such as
proliferation, apoptosis, the cytoskeleton dynamics, and the cellular response to
different stress factors. S100A6 can be secreted/released by certain cell types
which points to extracellular effects of the protein. RAGE (receptor for advanced
glycation endproducts) and integrin beta1 transduce some extracellular S100A6's
effects. Dosage of serum S100A6 might aid in diagnosis in oncology.
PMID- 28417163
TI - Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.
AB - Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell
physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a
substrate to a class of enzymes that catalyze non-redox reactions. These non
redox enzymes include the sirtuin family proteins which deacetylate target
proteins while cleaving NAD+ to yield NAM. Since the finding that NAM exerts
feedback inhibition to the sirtuin reactions, NAM has been widely used as an
inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role
in certain cell physiology. However, once administered to cells, NAM is rapidly
converted to NAD+ and, therefore, the cellular concentration of NAM decreases
rapidly while that of NAD+ increases. The result would be an inhibition of SIRT1
for a limited duration, followed by an increase in the activity. This possibility
raises a concern on the validity of the interpretation of the results in the
studies that use NAM as a SIRT1 inhibitor. To understand better the effects of
cellular administration of NAM, we reviewed published literature in which
treatment with NAM was used to inhibit SIRT1 and found that the expected
inhibitory effect of NAM was either unreliable or muted in many cases. In
addition, studies demonstrated NAM administration stimulates SIRT1 activity and
improves the functions of cells and organs. To determine if NAM administration
can generate conditions in cells and tissues that are stimulatory to SIRT1, the
changes in the cellular levels of NAM and NAD+ reported in the literature were
examined and the factors that are involved in the availability of NAD+ to SIRT1
were evaluated. We conclude that NAM treatment can hypothetically be stimulatory
to SIRT1.
PMID- 28417165
TI - Comparative study of outcomes after ankle arthrodesis shows higher complication
rates in cases operated upon by general orthopaedic surgeons.
AB - INTRODUCTION: A functional assessment of 38 patients after ankle arthrodesis for
the evaluation of the necessity of surgeons-specialisation was carried out by
means of clinical evaluation and gait analysis after an average follow up of 30
months. METHODS: Scores were used to grade ankle function. Gate analysis was
examined to determine the effect of arthrodesis on the ankle in relation to the
surgeons' experience. Under conditions of normal daily living, we found
significant differences in life quality between patients operated upon by experts
in orthopaedic foot and ankle surgery (group A) and patients operated by general
orthopaedic surgeons (group B). RESULTS: All patients in group A had orthograde
stance. Wrong screw positioning and a failed neutral tibio-talar position were
the main problems in group B. Due to this, the re-operation rate was 10%.
CONCLUSION: Our findings may have implications for surgical training programs and
for regionalisation of complex surgical procedures.
PMID- 28417164
TI - Individual differences in voluntary alcohol intake in rats: relationship with
impulsivity, decision making and Pavlovian conditioned approach.
AB - RATIONALE: Alcohol use disorder (AUD) has been associated with suboptimal
decision making, exaggerated impulsivity, and aberrant responses to reward-paired
cues, but the relationship between AUD and these behaviors is incompletely
understood. OBJECTIVES: This study aims to assess decision making, impulsivity,
and Pavlovian-conditioned approach in rats that voluntarily consume low (LD) or
high (HD) amounts of alcohol. METHODS: LD and HD were tested in the rat gambling
task (rGT) or the delayed reward task (DRT). Next, the effect of alcohol (0-1.0
g/kg) was tested in these tasks. Pavlovian-conditioned approach (PCA) was
assessed both prior to and after intermittent alcohol access (IAA). Principal
component analyses were performed to identify relationships between the most
important behavioral parameters. RESULTS: HD showed more optimal decision making
in the rGT. In the DRT, HD transiently showed reduced impulsive choice. In both
LD and HD, alcohol treatment increased optimal decision making in the rGT and
increased impulsive choice in the DRT. PCA prior to and after IAA was comparable
for LD and HD. When PCA was tested after IAA only, HD showed a more sign-tracking
behavior. The principal component analyses indicated dimensional relationships
between alcohol intake, impulsivity, and sign-tracking behavior in the PCA task
after IAA. CONCLUSIONS: HD showed a more efficient performance in the rGT and
DRT. Moreover, alcohol consumption enhanced approach behavior to reward
predictive cues, but sign-tracking did not predict the level of alcohol
consumption. Taken together, these findings suggest that high levels of voluntary
alcohol intake are associated with enhanced cue- and reward-driven behavior.
PMID- 28417166
TI - Vaccine impact in homogeneous and age-structured models.
AB - A general model of an imperfect vaccine for a childhood disease is presented and
the effects of different types of vaccine failure on transmission were
investigated using models that consider both homogeneous and age-specific mixing.
The models are extensions of the standard SEIR equations with an additional
vaccinated component that allows for five different vaccine parameters: three
types of vaccine failure in decreasing susceptibility to infection via failure in
degree ("leakiness"), take ("all-or-nothingness") and duration (waning of vaccine
derived immunity); one parameter reflecting the relative reduction in
infectiousness of vaccinated individuals who get infected; and one parameter that
reflects the relative reduction in reporting probability of vaccinated
individuals due to a possible reduction in severity of symptoms. Only the first
four parameters affect disease transmission (as measured by the basic
reproduction number). The reduction in transmission due to vaccination is
different for age-structured models than for homogeneous models. Notably, if the
vaccine exhibits waning protection this could be larger for an age-structured
model with high contact rates between young children who are still protected by
the vaccine and lower contact rates between adults for whom protection might have
already waned. Analytic expressions for age-specific "vaccine impacts" were also
derived. The overall vaccine impact is bounded between the age-specific impact
for the oldest age class and that of the youngest age class.
PMID- 28417168
TI - RDX degradation in bioaugmented model aquifer columns under aerobic and low
oxygen conditions.
AB - Degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in laboratory
columns following biostimulation and bioaugmentation was investigated using
sediment and groundwater from a contaminated aquifer at a US Navy facility. No
RDX degradation was observed following aerobic biostimulation with either
fructose or lactate (both 0.1 mM) prior to bioaugmentation. Replicate columns
were then bioaugmented with either Gordonia sp. KTR9, Pseudomonas fluorescens I-C
(Ps I-C), or both strains. Under aerobic conditions (influent dissolved oxygen
(DO) >6 mg/L), RDX was degraded following the addition of fructose, and to a
lesser extent with lactate, in columns bioaugmented with KTR9. No degradation was
observed in columns bioaugmented with only Ps I-C under aerobic conditions,
consistent with the known anaerobic RDX degradation pathway for this strain. When
influent DO was reduced to <2 mg/L, good RDX degradation was observed in the KTR9
bioaugmented column, and some degradation was also observed in the Ps I-C
bioaugmented column. After DO levels were kept below 1 mg/L for more than a
month, columns bioaugmented with KTR9 became unresponsive to fructose addition,
while RDX degradation was still observed in the Ps I-C-bioaugmented columns.
These results indicate that bioaugmentation with the aerobic RDX degrader KTR9
could be effective at sites where site geology or geochemistry allow higher DO
levels to be maintained. Further, inclusion of strains capable of anoxic RDX
degradation such as Ps I-C may facilitate bimodal RDX removal when DO levels
decrease.
PMID- 28417167
TI - Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a
useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in
preoperative chemoradiotherapy for patients with rectal cancer.
AB - PURPOSE: Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based
chemotherapy is the standard of care for rectal cancer. The effect of additional
chemotherapy during the period between the completion of radiotherapy and surgery
remains unclear. Predictive factors for CRT may differ between combination
chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). METHODS: The
subjects were 54 patients with locally advanced rectal cancer who received
preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed
according to the tumor regression grade (TRG). The expression levels of 18 CRT
related genes were determined using RT-PCR assay. RESULTS: A pathological
response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate
logistic regression analysis for pathological response, the overall expression
levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the
accuracy rate of the predictive model was 83.3%. The effects of the gene
expression levels of GGH on the response differed significantly according to the
treatment regimen. The total pathological response rate of both high-GGH patients
in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. CONCLUSION:
Additional treatment with 5-FU-based chemotherapy during the interval between
radiotherapy and surgery is not beneficial in patients who have received 5-FU
based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in
tumor tissues can predict the response to preoperative CRT including either S-1
or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may
be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.
PMID- 28417169
TI - Rational design of substrate binding pockets in polyphosphate kinase for use in
cost-effective ATP-dependent cascade reactions.
AB - Adenosine-5'-triphosphate (ATP) is the energy equivalent of the living system.
Polyphosphate (polyP) is the ancient energy storage equivalent of organisms.
Polyphosphate kinases (PPKs) catalyze the polyP formation or ATP formation, to
store energy or to regenerate ATP, respectively. However, most PPKs are active
only in the presence of long polyPs, which are more difficult and more expensive
to generate than the short polyPs. We investigated the PPK preference towards
polyPs by site-directed mutagenesis and computational simulation, to understand
the mechanism and further design enzymes for effective ATP regeneration using
short polyPs for in vitro cascade reactions, which are highly desired for
research and applications. The results suggest that the short polyPs inhibit PPK
by blocking the ADP-binding pocket. Structural comparison between PPK
(Corynebacterium glutamicum) and PPK (Sinorhizobium meliloti) indicates that
three amino acid residues, i.e., lysine, glutamate, and threonine, are involved
in the activity towards short polyP by fixing the adenosine group of ADP in
between the subunits of the dimer, while the terminal phosphate group of ADP
still offers an active site, which presents a binding pocket for ADP. A proposed
triple mutant PPK (SMc02148-KET) demonstrates significant activity towards short
polyP to form ATP from ADP. The obtained high glutathione titer (38.79 mM) and
glucose-6-phosphate titer (87.35 mM) in cascade reactions with ATP regeneration
using the triple mutant PPK (SMc02148-KET) reveal that the tailored PPK
establishes the effective ATP regeneration system for ATP-dependent reactions.
PMID- 28417170
TI - Reduced dose CT with model-based iterative reconstruction compared to standard
dose CT of the chest, abdomen, and pelvis in oncology patients: intra-individual
comparison study on image quality and lesion conspicuity.
AB - PURPOSE: To compare image quality and lesion conspicuity of reduced dose (RD) CT
with model-based iterative reconstruction (MBIR) compared to standard dose (SD)
CT in patients undergoing oncological follow-up imaging. METHODS: Forty-four
cancer patients who had a staging SD CT within 12 months were prospectively
included to undergo a weight-based RD CT with MBIR. Radiation dose was recorded
and tissue attenuation and image noise of four tissue types were measured.
Reproducibility of target lesion size measurements of up to 5 target lesions per
patient were analyzed. Subjective image quality was evaluated for three readers
independently utilizing 4- or 5-point Likert scales. RESULTS: Median radiation
dose reduction was 46% using RD CT (P < 0.01). Median image noise across all
measured tissue types was lower (P < 0.01) in RD CT. Subjective image quality for
RD CT was higher (P < 0.01) in regard to image noise and overall image quality;
however, there was no statistically significant difference regarding image
sharpness (P = 0.59). There were subjectively more artifacts on RD CT (P < 0.01).
Lesion conspicuity was subjectively better in RD CT (P < 0.01). Repeated target
lesion size measurements were highly reproducible both on SD CT (ICC = 0.987) and
RD CT (ICC = 0.97). CONCLUSIONS: RD CT imaging with MBIR provides diagnostic
imaging quality and comparable lesion conspicuity on follow-up exams while
allowing dose reduction by a median of 46% compared to SD CT imaging.
PMID- 28417171
TI - Resolution-optimized headspace gas chromatography-ion mobility spectrometry (HS
GC-IMS) for non-targeted olive oil profiling.
AB - A prototype gas chromatography-ion mobility spectrometry (GC-IMS) system,
hyphenating temperature-ramped headspace GC to a modified drift time IMS cell,
was evaluated and compared to a conventional, isothermal capillary column (CC)
IMS system on the example of the geographical differentiation of extra virgin
olive oils (EVOO) from Spain and Italy. It allows orthogonal, 2D separation of
complex samples and individual detection of compounds in robust and compact
benchtop systems. The information from the high-resolution 3D fingerprints of
volatile organic compound (VOC) fractions of EVOO samples were extracted by
specifically developed chemometric MATLAB(r) routines to differentiate between
the different olive oil provenances. A combination of unsupervised principal
component analysis (PCA) with two supervised procedures, linear discriminant
analysis (LDA) and k-nearest neighbors (kNN), was applied to the experimental
data. The results showed very good discrimination between oils of different
geographical origins, featuring 98 and 92% overall correct classification rate
for PCA-LDA and kNN classifier, respectively. Furthermore, the results showed
that the higher resolved 3D fingerprints obtained from the GC-IMS system provide
superior resolving power for non-targeted profiling of VOC fractions from highly
complex samples such as olive oil. Graphical abstract Principle of the
determination of geographic origins of olive oils by chemometric analysis of
three-dimensional HS-GC-IMS fingerprints.
PMID- 28417172
TI - Simultaneous determination of multiclass pesticide residues in human plasma using
a mini QuEChERS method.
AB - Blood is one of the most assessable matrices for the determination of pesticide
residue exposure in humans. Effective sample preparation/cleanup of biological
samples is very important in the development of a sensitive, reproducible, and
robust method. In the present study, a simple, cost-effective, and rapid gas
chromatography-tandem mass spectrometry method has been developed and validated
for simultaneous analysis of 31 multiclass (organophosphates, organochlorines,
and synthetic pyrethroids) pesticide residues in human plasma by means of a mini
QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. We have
adopted a modified version of the QuEChERS method, which is primarily used for
pesticide residue analysis in food commodities. The QuEChERS method was optimized
by use of different extraction solvents and different amounts and combinations of
salts and sorbents (primary-secondary amines and C18) for the dispersive solid
phase extraction step. The results show that a combination of ethyl acetate with
2% acetic acid, magnesium sulfate (0.4 g), and solid-phase extraction for sample
cleanup with primary-secondary amines (50 mg) per 1-mL volume of plasma is the
most suitable for generating acceptable results with high recoveries for all
multiclass pesticides from human plasma. The mean recovery ranged from 74% to
109% for all the analytes. The limit of quantification and limit of detection of
the method ranged from 0.12 to 13.53 ng mL-1 and from 0.04 to 4.10 ng mL-1
respectively. The intraday precision and the interday precision of the method
were 6% or less and 11% or less respectively. This method would be useful for the
analysis of a wide range of pesticides of interest in a small volume of clinical
and/or forensic samples to support biomonitoring and toxicological applications.
Graphical Abstract Pesticide residues analysis in human plasma using mini
QuEChERS method.
PMID- 28417173
TI - Semiautomated TaqMan PCR screening of GMO labelled samples for (unauthorised)
GMOs.
AB - In most countries, systems are in place to analyse food products for the
potential presence of genetically modified organisms (GMOs), to enforce labelling
requirements and to screen for the potential presence of unauthorised GMOs. With
the growing number of GMOs on the world market, a larger diversity of methods is
required for informative analyses. In this paper, the specificity of an extended
screening set consisting of 32 screening methods to identify different crop
species (endogenous genes) and GMO elements was verified against 59 different GMO
reference materials. In addition, a cost- and time-efficient strategy for DNA
isolation, screening and identification is presented. A module for semiautomated
analysis of the screening results and planning of subsequent event-specific tests
for identification has been developed. The Excel-based module contains
information on the experimentally verified specificity of the element methods and
of the EU authorisation status of the GMO events. If a detected GMO element
cannot be explained by any of the events as identified in the same sample, this
may indicate the presence of an unknown unauthorised GMO that may not yet have
been assessed for its safety for humans, animals or the environment.
PMID- 28417174
TI - Multidimensional single-cell analysis based on fluorescence microscopy and
automated image analysis.
AB - A single-cell analytical technology was developed for evaluating fast-growing
cultures of green algae. The main part of the single-cell analysis is an
epifluorescence microscopy-based cytometric approach combined with an automated
image analysis algorithm and a single-threshold discrimination procedure. The
reliability of the technique in terms of object recognition, evaluating particle
size, and determining chlorophyll was successfully proven via reference analyses.
The microscopy technique was used to determine the size of single cells, the
amount of chlorophyll, and the density of chlorophyll in a model algal culture
(Acutodesmus o.). The algal cells showed unexpected heterogeneity in all single
cell parameters, and exhibited a high correlation between cell size and amount of
chlorophyll but a very low correlation between cell size and chlorophyll density.
For a given cell size, the cell-to-cell heterogeneity of the relative chlorophyll
density showed a spread of 0.02-0.08. This points to large variations in the
architecture and the physiological state of the photosynthetic apparatus in the
cells. This complex situation should be considered in future systems biology
approaches focusing on the relationships between biomass accumulation,
photosynthetic activity, and central carbon metabolism. Graphical abstract
Analysis of cell-to-cell heterogeneity obtained from microscopic images.
PMID- 28417175
TI - Microwave-assisted deglycosylation for rapid and sensitive analysis of N-glycans
via glycosylamine derivatization.
AB - A rapid and sensitive N-glycan profiling strategy for MALDI-MS incorporating the
use of deglycosylation with microwave assistance and the co-derivatization of
glycosylamine labeling with tris(2,4,6-trimethoxyphenyl)phosphonium acetic acid N
hydroxysuccinimide ester (TMPP-Ac-OSu) and methylamidation has been developed in
this work. Notably, highly efficient release and tagging of N-glycans from
ribonuclease B was achieved in less than 90 min, providing up to 35-fold
enhancement of MALDI-MS sensitivity with comparison to underivatized N-glycans.
After further validation with other two standard glycoproteins (ovalbumin and
bovine fetuin), the proposed strategy was applied to human serum for preliminary
pathological analysis of N-glycans between healthy and lung cancer individuals.
As a result, significant differences (T test p value <0.01) of 6 glycan
structures were determined from 54 detected N-glycan structures with only 50 nL
of loading amount and further confirmed through PCA and ROC (AUC) analyses
between two sample sets. Subsequently, the trend of each lung cancer stage and
controls in expression of the selected glycans was implemented with T test and
box-plots. Accordingly, these structures can be used as potential lung cancer
glycan-based biomarkers and for further definition of cancer progression
highlighting the ability of proposed method to rapidly and efficiently analyze N
glycome present in human serum. Graphical abstract MALDI-TOF MS analysis of N
glycans by microwave-assisted deglycosylation and glycosylamine derivatization.
PMID- 28417177
TI - In-situ hydrothermal synthesis of titanium dioxide nanorods on titanium wire for
solid-phase microextraction of polycyclic aromatic hydrocarbons.
AB - Titanium dioxide nanorods were prepared on the surface of titanium wire by
hydrothermal synthesis for use as a solid-phase microextraction (SPME) fiber. The
morphology of the SPME coating was observed by scanning electron microscopy
(SEM). Employed in conjunction with gas chromatography (GC), the fiber was
investigated with five polycyclic aromatic hydrocarbons (PAHs) and three
terphenyls in direct-immersion extraction mode. Various parameters were
optimized, such as the extraction time, the stirring rate, the extraction
temperature, the ionic strength of the sample solution, and the desorption time.
Under the optimized conditions, the SPME-GC analytical method achieved a low
detection limit (0.003 MUg L-1) and wide linear ranges (0.01-100 MUg L-1 and 0.01
200 MUg L-1) along with good correlation coefficients (0.9892-0.9962). The
established method was also used to analyze rainwater and an aqueous solution of
coal ash. The results indicated that this fiber could be applied in real-world
environmental monitoring. The proposed fiber also exhibited excellent durability.
Graphical Abstract The schematic diagram of experimental process.
PMID- 28417176
TI - Functional gold nanoparticles for optical affinity biosensing.
AB - Functional gold nanoparticles (AuNPs) are commonly used to enhance the response
of optical affinity biosensors. In this work, we investigated the effect of
preparation conditions on functional properties of AuNPs functionalized with
antibody (Ab-AuNPs), specifically AuNPs with antibody against carcinoembryonic
antigen (CEA) covalently attached via carboxy-terminated oligo-ethylene thiolate
linker layer. The following parameters of preparation of Ab-AuNP have been found
to have a significant effect on Ab-AuNP performance in affinity biosensors: the
time of reaction of activated AuNPs with antibody, concentrations of antibody and
amino-coupling reagents, and composition of immobilization buffer (molarity and
salt content). In contrast, pH of immobilization buffer has been demonstrated to
have only a minor influence. Our experiments showed that the Ab-AuNPs prepared
under optimum conditions offered a binding efficiency of Ab-AuNPs to CEA as high
as 63%, which is more than 4 times better than the best efficiencies reported for
similar functional AuNPs so far. We employed these Ab-AuNPs with a surface
plasmon resonance (SPR) biosensor for the detection of CEA and showed that the Ab
AuNPs enhanced the sensor response to CEA by a factor of 1000. We also
demonstrated that the Ab-AuNPs allow the biosensor to detect CEA at
concentrations as low as 12 and 40 pg/mL in buffer and 50% blood plasma,
respectively.
PMID- 28417178
TI - Highly sensitive and selective determination of hydrogen sulfide by resonance
light scattering technique based on silver nanoparticles.
AB - We have developed a green approach to prepare DNA-templated silver nanoparticles
(Ag-NPs) from the direct reaction between Ag+ and ascorbic acid in the presence
of DNA and sodium hydroxide. The Ag-NPs showed strong resonance light scattering
(RLS) intensity property. Then, the interaction between hydrogen sulfide (H2S)
and Ag-NPs was studied by measuring their RLS spectra. The results showed that
there is a strong interaction between Ag-NPs and H2S, which resulted in a
decrease in the size of Ag-NPs and a decrease in the RLS intensity of the Ag-NPs
solution at the wavelength of 467 nm. The results demonstrated that the RLS
technique offers a sensitive and simple tool for investigating the interaction
between Ag-NPs and H2S, which can be applied to detect H2S with high sensitivity
and selectivity without complex readout equipment. The linear range for H2S
determination was found to be the range from 5.0 * 10-9 to 1.0 * 10-7 mol L-1,
and the detection limit (3sigma/k) was 2.8 * 10-9 mol L-1. Moreover, the proposed
method was applied for the determination of H2S in natural water samples with
satisfactory results. Graphical abstract The application of Ag-NPs in H2S
detection.
PMID- 28417179
TI - Analysis of honeybush tea (Cyclopia spp.) volatiles by comprehensive two
dimensional gas chromatography using a single-stage thermal modulator.
AB - The applicability of comprehensive two-dimensional gas chromatography (GC*GC)
using a single-stage thermal modulator was explored for the analysis of honeybush
tea (Cyclopia spp.) volatile compounds. Headspace solid phase micro-extraction
(HS-SPME) was used in combination with GC*GC separation on a non-polar * polar
column set with flame ionisation (FID) detection for the analysis of fermented
Cyclopia maculata, Cyclopia subternata and Cyclopia genistoides tea infusions of
a single harvest season. Method optimisation entailed evaluation of the effects
of several experimental parameters on the performance of the modulator, the
choice of columns in both dimensions, as well as the HS-SPME extraction fibre.
Eighty-four volatile compounds were identified by co-injection of reference
standards. Principal component analysis (PCA) showed clear differentiation
between the species based on their volatile profiles. Due to the highly
reproducible separations obtained using the single-stage thermal modulator,
multivariate data analysis was simplified. The results demonstrate both the
complexity of honeybush volatile profiles and the potential of GC*GC separation
in combination with suitable data analysis techniques for the investigation of
the relationship between sensory properties and volatile composition of these
products. The developed method therefore offers a fast and inexpensive
methodology for the profiling of honeybush tea volatiles. Graphical abstract
Surface plot obtained for the GC*GC-FID analysis of honeybush tea volatiles.
PMID- 28417180
TI - Multiplexed assay for protein quantitation in the invertebrate Gammarus fossarum
by liquid chromatography coupled to tandem mass spectrometry.
AB - A highly multiplexed liquid chromatography mass spectrometry-selected reaction
monitoring (SRM)-based assay for determination of 40 potential protein biomarkers
from Gammarus fossarum, an ecotoxicological relevant species, was described. The
assay relies on 71 stable isotope-labeled reported peptide standards for the
quantitation of proteins of interest in relation to essential physiological
functions such as reproductive cycle, defense mechanism, and enzymes involved in
homeostasis process and in energy. A direct linear relationship between the
spiked peptide concentration and the area under the peak was clearly demonstrated
in biological extracts. Precision and accuracy were determined to be between 1.1
and 21% and between 79 and 120%, respectively, depending on the selected protein
in a few samples after optimization of digestion conditions. The validity of the
assay was documented for several biomarkers linked with reproduction and the
molting process was performed with the assessment of protein levels throughout
contrasted physiological process (sex, reproductive status). This assay is easy
to use, robust, sensitive, and has high-throughput capabilities. The proposed
strategy may be extended to any non-model organisms relevant in environmental
science. Graphical abstract ?.
PMID- 28417181
TI - Colonic inflammation in pediatric inflammatory bowel disease: detection with
magnetic resonance enterography.
AB - BACKGROUND: Colonic involvement in pediatric inflammatory bowel disease is
common. Magnetic resonance (MR) enterography is considered the best imaging
modality for pediatric inflammatory bowel disease evaluation. It is unclear
whether the lack of a dedicated large bowel preparation prevents a reliable
colonic assessment. OBJECTIVE: To determine the diagnostic performance of
standard MR enterography in detecting and grading colonic inflammatory activity.
MATERIALS AND METHODS: We retrospectively evaluated children who underwent both
MR enterography and ileocolonoscopy with biopsies <4 weeks apart. Two
radiologists independently reviewed MR examinations and quantified inflammation
in each of the five colonic segments using a standardized MR score system.
Findings were compared with histological examination of the corresponding
segment. Mann-Whitney, Kruskal-Wallis, Jonckheere-Terpstra and Bland-Altman
statistics were used. RESULTS: One hundred seventy-five segments from 37
examinations were included. MR enterography diagnostic performance for
inflammation was as follows: sensitivity 94% (95% confidence interval [CI]: 90
97%), specificity: 64% (95% CI: 57-71%). A significant positive correlation was
found between MR score and inflammatory activity histologically graded (P<0.001,
Jonckheere-Terpstra test). The interobserver agreement was good (mean difference
between MR enterography scores was -0.03; limits of agreement -2.8 to 2.7).
CONCLUSION: Standard MR enterography is sensitive for the detection of actively
inflamed colonic segments. MR enterography might provide useful information for
guiding biopsies and its role as an alternative to ileocolonoscopy in monitoring
colonic disease activity in children should be further investigated.
PMID- 28417183
TI - Patella height is not altered by descending medial open-wedge high tibial
osteotomy (HTO) compared to ascending HTO.
AB - PURPOSE: The primary purpose of the study was to gain insight into geometric
changes of the patellar height (PH) and posterior tibial slope (PTS) after a
biplanar ascending medial open-wedge high tibial osteotomy (HTO) compared to
biplanar descending medial open-wedge HTO in patients with genu varum. METHODS:
Sixty-four patients (mean age 45.2 +/- 8.7 years, females n = 24, males n = 40)
with varus malalignment and medial gonarthrosis were retrospectively studied.
Patients received either a biplanar ascending or descending medial open-wedge
HTO. Radiographic analysis included the assessment of standing total leg axis,
PH, and PTS prior to and after surgery. RESULTS: In the ascending HTO group, PH
decreased significantly by 4.0% (p = 0.037, Caton-Deschamps index) after an
average leg axis valgus-producing correction of 7.1 degrees +/- 2.8 degrees . In
the descending HTO group, with an average leg axis correction of 7.0 degrees +/-
3.7 degrees , there were no significant PH changes. There were no significant
differences between the ascending and descending HTO groups regarding PTS or leg
axis. The mean post-operative leg axis between ascending (1.6 degrees +/- 1.9
degrees ) and descending HTO (1.9 degrees +/- 2.4 degrees ) was not
significantly different. CONCLUSION: Compared to the biplanar ascending medial
open-wedge HTO, the descending HTO did not influence patella height or increase
the posterior tibial slope. In order to respect patellofemoral and slope-related
knee kinematics, a biplanar descending medial open-wedge HTO has proven useful to
control patella height and posterior tibial slope. These findings underscore the
importance of the preoperative patella height assessment in the osteotomy
planning and subsequent choice of the biplanar osteotomy direction. LEVEL OF
EVIDENCE: IV.
PMID- 28417185
TI - Combined Preoperative Portal and Hepatic Vein Embolization (Biembolization) to
Improve Liver Regeneration Before Major Liver Resection: A Preliminary Report.
AB - BACKGROUND: Insufficient volume of the future liver remnant (FLR) is a major
cause of non-resectable disease in patients presenting with primary or metastatic
liver tumours. The objective of this study was to evaluate the safety and
efficacy of the combined preoperative portal and hepatic vein embolization
(biembolization) before extended right liver resections. METHODS: This
retrospective study was performed in a tertiary centre between 2014 and 2015.
Combined right portal and hepatic vein embolization (biembolization) was
proposed, as an alternative to ALPPS procedure, for all patients with primary or
metastatic liver tumour, before right extended hepatectomy. CT scan liver
volumetry was assessed before biembolization, three weeks after biembolization
and one week after surgery. RESULTS: Seven patients underwent biembolization. All
patients had right portal vein embolization (PVE) combined with right hepatic
vein embolization (HVE, n = 4), median HVE (n = 2) and right + median HVE (n =
1). Three patients had preoperative liver disease and two received preoperative
chemotherapy. No biembolization procedure-related complications occurred. The
mean FLR regeneration rate was 52.6% (range: 18.2-187.9) after the
biembolization. One patient with gallbladder carcinoma was not operated because
of peritoneal carcinomatosis diagnosed after the biembolization. The remnant six
patients did not develop postoperative liver failure. CONCLUSIONS: Biembolization
seems to induce safe, reproducible and effective FLR growth before extended right
hepatectomy, in patients with primary or metastatic liver tumour.
PMID- 28417184
TI - Comparison of Epidemiology of the Injuries and Outcomes in Two First-Level Trauma
Centers in Colombia Using the Pan-American Trauma Registry System.
AB - INTRODUCTION: The aim of this study was to compare the epidemiology of traumatic
injuries and mortality outcomes between two tertiary-care trauma centers in
Colombia using data from Pan-American Trauma Registry (PATR). METHODS: January 1
December 31, 2012, data from the Hospital Universitario del Valle (HUV, public)
and Fundacion Valle del Lili (FVL, private) in Cali, Colombia, were considered.
Differences in demographic and clinical information were compared using
descriptive statistics. Propensity score matching was used to match patients on
age, gender, and ISS. Within matched cohorts, multivariable logistic regression
models were used to assess for differences in in-hospital mortality, further
adjusting for insurance type, employment, heart rate, presence of hypotension
(SBP < 90), and GCS score. RESULTS: HUV (8539; 78% male) and FVL (10,456; 60%
male) had a combined total of 18,995 trauma cases in 2012 with comparable mean
ages of 29.7 years. There were significant differences in insurance status,
injury severity, and mechanism of injury between patients at HUV and FLV. On risk
adjusted logistic regression analyses with propensity score matched cohorts, the
odds of death in HUV was higher compared to patients presenting at FVL hospital
(OR [95% CI]:4.93 [3.37-7.21], p < 0.001). CONCLUSION: The study established the
utility of the PATR and revealed important trends in patient demographics, injury
epidemiology, and mortality outcomes, which can be used to target trauma
initiatives throughout the region. It underscores the profound importance that
differences in case mix play in the risk of trauma-related mortality, further
emphasizing the need to monitor and evaluate unique aspects of trauma in LMIC.
LEVEL OF EVIDENCE: III.
PMID- 28417186
TI - Endoscopic Central Lymph Node Dissection via Breast Combined with Oral Approach
for Papillary Thyroid Carcinoma: A Preliminary Study.
AB - OBJECTIVE: To investigate the feasibility and necessity of endoscopic
thyroidectomy with central lymph node dissection via the combined breast and
trans-oral approaches. METHODS: Six patients with papillary thyroid carcinoma who
underwent endoscopic total thyroidectomy with central node dissection via
combined breast and trans-oral approaches from November 2014 to January 2015 in
Zhongshan Hospital, Xiamen University, were analyzed. RESULTS: After completion
of endoscopic central lymph node dissection via the traditional breast approach,
eight pieces of lymph nodes could still be dissected via the trans-oral approach.
Two of these eight pieces were positive for thyroid cancer metastasis.
CONCLUSIONS: It is advisable to perform endoscopic central lymph node dissection
for thyroid carcinoma via the breast approach combined with the trans-oral
approach.
PMID- 28417188
TI - Comparative Transcriptome Sequence Analysis of Sporulation-Related Genes of
Aspergillus cristatus in Response to Low and High Osmolarity.
AB - Aspergillus cristatus undergoes sexual and asexual development under conditions
of low and high osmotic pressure, respectively. In this study, the expression
levels of 107 genes associated with sexual and asexual development were analysed
under conditions of low and high osmotic pressure by RNA sequencing. The results
showed that 37 genes were up-regulated and other genes were down-regulated under
conditions of high osmotic pressure, with most of the up-regulated genes
associated with asexual development and most down-regulated genes associated with
sexual development. These results suggest that osmotic pressure regulated sexual
and asexual development of A. cristatus by controlling the expression levels of
key genes. Meanwhile, there were differences in the expression levels of key
genes associated with the regulation of sexual and asexual development between A.
cristatus and Aspergillus nidulans. Moreover, we verified the reliability of the
results by quantitative real-time polymerase chain reaction analysis of some key
genes. In this study, the relationship between sporulation-related genes and
osmotic pressure at the transcriptome level were analysed, which indicated that
A. cristatus was a useful model organism for the study of osmotic pressure
regulation on sexual and asexual development.
PMID- 28417189
TI - Draft Genome Sequence of a Biosurfactant-Producing Bacillus subtilis UMX-103
Isolated from Hydrocarbon-Contaminated Soil in Terengganu, Malaysia.
AB - The draft genome here presents the sequence of Bacillus subtilis UMX-103. The
bacterial strain was isolated from hydrocarbon-contaminated soil from Terengganu,
Malaysia. The whole genome of the bacterium was sequenced using Illumina HiSeq
2000 sequencing platform. The genome was assembled using de novo approach. The
genome size of UMX-103 is 4,234,627 bp with 4399 genes comprising 4301 protein
coding genes and 98 RNA genes. The analysis of assembled genes revealed the
presence of 25 genes involved in biosurfactant production, where 14 of the genes
are related to biosynthesis and 11 of the genes are in the regulation of
biosurfactant productions. This draft genome will provide insights into the
genetic bases of its biosurfactant-producing capabilities.
PMID- 28417187
TI - Isolation of Viable but Non-culturable Bacteria from Printing and Dyeing
Wastewater Bioreactor Based on Resuscitation Promoting Factor.
AB - Printing and dyeing wastewater with high content of organic matters, high
colority, and poor biochemical performance is hard to be degraded. In this study,
we isolated viable but non-culturable (VBNC) bacteria from printing and dyeing
wastewater with the culture media contained resuscitation promoting factor (Rpf)
protein secreted by Micrococcus luteus, counted the culturable cells number with
the most probable number, sequenced 16S rRNA genes, and performed polymerase
chain reaction-denaturing gradient gel electrophoresis. It is obviously that the
addition of Rpf in the enrichment culture could promote growth and resuscitation
of bacteria in VBNC state to obtain more fastidious bacteria significantly. The
identified bacteria were assigned to nine genera in the treatment group, while
the two strains of Ochrobactrum anthropi and Microbacterium sp. could not be
isolated from the control group. The function of isolated strains was explored
and these strains could degrade the dye of Congo red. This study provides a new
sight into the further study including the present state, composition, formation
mechanism, and recovery mechanism about VBNC bacteria in printing and dyeing
wastewater, which would promote to understand bacterial community in printing and
dyeing wastewater, and to obtain VBNC bacteria from ecological environment.
PMID- 28417190
TI - Larkinella harenae sp. nov., Isolated from Korean Beach Soil.
AB - A Gram-negative, short rod-shaped, gliding motile, and pale pink-pigmented
bacterial strain, designated 15J9-9T, was isolated from the soil of Iho Tewoo
Beach, Jeju Island, Korea, and characterized taxonomically using a polyphasic
approach. Comparative 16S rRNA gene sequence analysis showed that strain 15J9-9T
belonged to the family Cytophagaceae and was related to Larkinella bovis M2T2B15T
(96.5% similarity), Larkinella arboricola Z0532T (95.3% similarity), and
Larkinella insperata LMG 22510T (95.2% similarity). The DNA G+C content of strain
15J9-9T was 48 mol%. The detection of phosphatidylethanolamine,
phosphatidylserine, two unknown aminophospholipids (APL1 and APL2), and two
unknown polar lipids (L1 and L2) in polar lipid profile, menaquinone-7 as the
predominant quinone, and a fatty acid profile of C16:1 omega5c, iso-C15:0, and
iso-C17:0 3-OH as the major fatty acids supported the affiliation of strain 15J9
9T to the genus Larkinella. Based on its phenotypic properties and phylogenetic
distinctiveness, strain 15J9-9T should be classified in the genus Larkinella as a
representative of a novel species, for which the name Larkinella harenae sp. nov.
is proposed. The type strain is 15J9-9T (=KCTC 42999T = JCM 31656T).
PMID- 28417191
TI - Mapping of estradiol binding sites through receptor micro-autoradiography in the
endometrial stroma of early pregnant mice.
AB - Estradiol triggers key biological responses in the endometrium, which rely on the
presence and levels of its cognate receptors on target cells. Employing the
receptor micro-autoradiography (RMAR) technique, we aimed to provide a temporal
and spatial map of the functional binding sites for estradiol in the mouse
endometrial stroma during early pregnancy. Uterine samples from days 1.5 to 7.5
of pregnancy were collected 1 h after tritiated- (3H-) estradiol administration
and prepared for RMAR analysis. Autoradiographic incorporation of 3H-thymidine
(after 1-h pulse) was evaluated over the same gestational interval. Combined RMAR
with either histochemistry with Dolichus biflorus (DBA) lectin or
immunohistochemistry for detection of the desmin further characterized 3H
estradiol binding pattern in uterine Natural Killer (uNK) and decidual cells,
respectively. 3H-estradiol binding levels oscillated in the pregnant endometrial
stroma between the mesometrial and antimesometrial regions as well as the
superficial and deep domains. Although most of the endometrial stromal cells
retained the hormone, a sub-population of them, as well as endothelial and uNK
cells, were unable to do so. Rises in the levels of 3H-estradiol binding preceded
endometrial stromal cell proliferation. 3H-estradiol binding and 3H-thymidine
incorporation progressively decreased along the development of the
antimesometrial decidua. Endothelial proliferation occurred regardless of 3H
estradiol binding, whereas pericytes proliferation was associated with high
levels of hormone binding. Endometrial cell populations autonomously control
their levels of 3H-estradiol binding and retention, a process associated with
their proliferative competence. Collectively, our results illustrate the
intricate regulatory dynamic of nuclear estrogen receptors in the pregnant mouse
endometrium.
PMID- 28417192
TI - Can we predict benign multiple sclerosis? Results of a 20-year long-term follow
up study.
AB - Benign multiple sclerosis (MS) is a discussed clinical entity, with variable
reported prevalence (6-64%) requiring at least 5-10 years of clinical
observation. Moreover, many benign patients progress with time becoming no longer
benign (NLB). The objective of this study is to compare benign MS patients (EDSS
<=3, 10 years from disease onset) who still fulfilled the definition at 20 years
to those NLB. In our retrospective study based on Ottawa Hospital MS Clinic
database, 175 benign patients fulfilled the inclusion criteria (clinically
definite MS, EDSS <=3 at 10 years, disease onset from 1983 to 1993, and clinical
assessments performed at 10 +/- 1 and 20 +/- 1 years from onset). Out of the
identified patients, 66.3% remained benign at 20 years; however, by changing the
definition for benign to EDSS <=2 or <=1 at 10 years, they increased to 71.9 and
81.6%, respectively. Female sex, EDSS <=1 at 10 years, and a pure sensory onset
were associated with a benign course, while a pure motor onset with an NLB
condition. According to multivariate analysis, an EDSS <=2 at 10 years predicted
a long-term benign course. Our study questions the current definition of "benign"
MS, suggesting a more stringent EDSS cutoff at 10 years to predict long-term
benign prognosis.
PMID- 28417193
TI - Genome-wide analysis of VQ motif-containing proteins in Moso bamboo
(Phyllostachys edulis).
AB - MAIN CONCLUSION: 29 Moso bamboo VQ proteins were genome-wide identified for the
first time, and bioinformatics analysis was performed to investigate phylogenetic
relationships and evolutionary divergence. The qRT-PCR data show that PeVQ genes
response to different stress treatments. Accumulating evidence suggests that VQ
motif-containing proteins in rice (Oryza sativa), Arabidopsis (Arabidopsis
thaliana), and maize (Zea mays) play fundamental roles in response to various
biotic and abiotic stresses. However, little is known about the functions of VQ
family proteins in Moso bamboo (Phyllostachys edulis). In this study, we
performed a genome-wide bioinformatic analysis and expression profiling of PeVQ
genes. A total of 29 VQ genes was identified and divided into seven subgroups (I
VII) based on phylogenetic analysis. Gene structure and conserved motif analysis
revealed that 25 of 29 VQ genes contained no introns. Multiple sequence alignment
showed that Moso bamboo VQ motif-containing proteins contained five variations of
the conserved motif. The time of duplication and divergence of Moso bamboo from
rice and maize was calculated using K s analysis. A heat map was generated using
microarray data from 29 Moso bamboo VQ genes suggesting that these genes were
expressed in different tissues or developmental stages. Quantitative real-time
PCR (qRT-PCR) and promoter analysis indicated that PeVQ genes were differentially
regulated following treatment with polyethylene glycol, abscisic acid and
salicylic acid. Our results provide a solid foundation for further research of
the specific functions of VQ motif-containing proteins in Moso bamboo.
PMID- 28417194
TI - Impact of BCL2 polymorphisms on survival in transitional cell carcinoma of the
bladder.
AB - PURPOSE: To evaluate the impact of three BCL2 single-nucleotide polymorphisms,
i.e., c.-938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on
survival in patients with transitional cell carcinoma of the bladder. METHODS: We
analyzed 179 patients who underwent surgical treatment for bladder cancer at the
Clinic of Urology, University Hospital Essen, Germany. Genomic DNA was extracted
and genotyped for the polymorphisms. For all polymorphisms, linkage analysis was
performed. Kaplan-Meier and Cox regression analyses were used to determine the
putative impact of the three polymorphisms on outcome. RESULTS: c.-938C>A and
c.21G>A, but not c.*2203A>G, are in strong linkage disequilibrium (D' 0.96). We
found a significant association between c.-938C>A and relapse-free survival (p =
0.024) with an allele dose effect. In the same way, c.21G>A had a significant
impact on both relapse-free survival (p = 0.009) and progression-free survival (p
= 0.012), as well as a pronounced allele dose effect. Regression analysis proved
c.21G>A and c.-938C>A, to be an independent risk factor in univariate and
multivariable analyses. CONCLUSIONS: In our cohort, both c.-938C>A and c.21G>A
showed a significant impact on outcome with TCC of the bladder. Due to the
linkage disequilibrium of both SNPs, maybe, only one of them could mediate this
effect. In multivariable analysis, however, both proved to be independently
associated with overall survival. Contrary to other findings which found the c.
938C>A mainly influencing outcome, our data may suggest that the main effect on
TCC could be due to the c.21G>A polymorphism.
PMID- 28417195
TI - RRx-001 protects against cisplatin-induced toxicities.
AB - PURPOSE: RRx-001, a minimally toxic tumor-associated macrophage and neutrophil
repolarizing agent, is under investigation in Phase II clinical trials as a
sensitizer/resensitizer to cisplatin and carboplatin. On the basis of anecdotal
clinical observations of improved platinum tolerability following a priming
period with RRx-001 as well as preclinical studies that have previously
demonstrated radioprotection of intestinal stem cells and cardioprotection from
doxorubicin, the in vivo cytoprotective potential of RRx-001 pretreatment against
cisplatin-induced bone marrow suppression and renal toxicity was investigated.
METHODS: BALB/c mice were divided into three groups: (1) no treatment, (2)
vehicle and cisplatin only, and (3) RRx-001 and cisplatin. RRx-001 treatment (5
mg/kg every other day for 3 days) was initiated 3 days prior to cisplatin
administration. Blood was collected from the femoral vein at different intervals
to measure total hemoglobin and leukocyte counts as well as renal functional
markers (serum urea, creatinine and creatinine clearance). Metaphase spreads were
prepared from whole bone marrow cells as markers of clastogenicity. RESULTS: RRx
001 pretreatment significantly decreased (P < 0.05) the blood urea nitrogen and
creatinine levels. A statistically significant (P < 0.05) reduction in the mean
total chromosome aberration frequency per metaphase in the RRx-001 and cisplatin
group compared to the cisplatin-only group was observed. CONCLUSIONS: This study
is the first to demonstrate that RRx-001 has nephro-, geno- and myeloprotective
effects in vivo. Importantly, RRx-001 did not protect sarcoma-180 solid tumor
xenografts against cisplatin-induced cytotoxicity. These results potentially
support the use of RRx-001 as a chemoprotector against cisplatin-induced
toxicities.
PMID- 28417196
TI - A sustaining rod increases necrosis of loop ileostomies: a randomized controlled
trial.
AB - PURPOSE: Defunctioning loop ileostomies (LI) are commonly used in colorectal
surgery to reduce the potentially detrimental consequences of anastomotic
leakages. However, stoma-related morbidity is high with up to 75% of patients
having local complications. The aim of this study was to investigate the effect
of a sustaining rod on the local complication rate. METHODS: In this prospective,
multi-center, randomized controlled trial, subjects were allocated to either a
rod or a rod-less protocol (NCT00959738). The primary outcome was local morbidity
as measured by a stoma specific morbidity score (SSMS) during the first 3 months
postoperatively. RESULTS: Between August 2008 and July 2014, a total of 122
patients were enrolled in the study, of which 78 (63.8%) completed the study [44
(56.4%) rod, 34 (43.6%) rod-less]. There was no significant difference in the
SSMS between the two groups. The incidence of necrosis or partial necrosis,
however, was significantly increased in the rod group: 13 (29.5%) vs. 1 (2.9%) in
the rod-less group (p < 0.01). The retraction rate did not differ significantly
between the groups: two (4.5%) in the rod vs. five (14.7%) in the rod-less group
(p = 0.13). High body mass index (BMI > 26) was associated with an odds ratio of
5 (p < 0.01) for severe stoma complications. CONCLUSIONS: A rod-less technique
for loop ileostomies reduces the risk of stomal necrosis, with a high BMI being
an independent risk factor for stomal complications.
PMID- 28417197
TI - Origin, Function, and Fate of Metallothionein in Human Blood.
AB - Toxic heavy metals, toxic organic compounds, reactive oxygen species (ROS),
infections, and temperature are well-known metallothionein (MT) inducers in human
blood. The current review aims to summarize synthesis, function, and fate of
human blood MT in response to the known MT inducers. Part of the MTs that are
synthesized in different organs such as the liver, kidney, and spleen is
transported and stored in different blood cells and in plasma. Cells of the
circulatory system also synthesize MT. From the circulation, MT returns to the
kidney where the metal-bound MTs are degraded to release the metal ion that in
turn induces MT expression therein. The blood MTs play important roles in metal
detoxification, transportation, and storage. By neutralizing ROS, MTs protect
blood cells from oxidative stress-induced cytotoxicity and genotoxicity.
Arguably, MTs are also involved in immune suppression. Given the permeating
distribution of blood MT throughout the body as well as its diverse role in the
protection against harmful environmental factors and in metal homeostasis, MT
could be better recognized as a major public health protein.
PMID- 28417198
TI - Biases in the production and reception of collective knowledge: the case of
hindsight bias in Wikipedia.
AB - The Web 2.0 enabled collaboration at an unprecedented level. In one of the
flagships of mass collaboration-Wikipedia-a large number of authors socially
negotiate the world's largest compendium of knowledge. Several guidelines in
Wikipedia restrict contributions to verifiable information from reliable sources
to ensure recognized knowledge. Much psychological research demonstrates,
however, that individual information processing is biased. This poses the
question whether individual biases translate to Wikipedia articles or whether
they are prevented by its guidelines. The present research makes use of hindsight
bias to examine this question. To this end, we analyzed foresight and hindsight
versions of Wikipedia articles regarding a broad variety of events (Study 1). We
found the majority of articles not to contain traces of hindsight bias-contrary
to prior individual research. However, for a particular category of events
disasters-we found robust evidence for hindsight bias. In a lab experiment (Study
2), we then examined whether individuals' hindsight bias is translated into
articles under controlled conditions and tested whether collaborative writing-as
present in Wikipedia-affects the resultant bias (vs. individual writing).
Finally, we investigated the impact of biased Wikipedia articles on readers
(Study 3). As predicted, biased articles elicited a hindsight bias in readers,
who had not known of the event previously. Moreover, biased articles also
affected individuals who knew about the event already, and who had already
developed a hindsight bias: biased articles further increased their hindsight.
PMID- 28417199
TI - Intake of 7,8-dihydroxyflavone from pregnancy to weaning prevents cognitive
deficits in adult offspring after maternal immune activation.
AB - Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor,
tropomyosin receptor kinase B (TrkB) signaling plays a key role in the brain
neurodevelopment. The exposure of pregnant mice to polyinosinic-polycytidylic
acid [poly(I:C)] causes cognitive deficits in adult offspring. Supplementation
with a TrkB agonist, 7,8-dihydroxyflavone, in poly(I:C)-treated pregnant mice
from pregnancy to weaning could prevent the onset of cognitive deficits and
reduced BDNF-TrkB signaling in the prefrontal cortex of their adult offspring.
These findings suggest that supplementation with a TrkB agonist in pregnant women
with an ultra-high risk of psychosis may reduce the development of psychosis in
their offspring.
PMID- 28417200
TI - HPV-related carcinomas of the head and neck: morphologic features, variants, and
practical considerations for the surgical pathologist.
AB - Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma is a
distinct tumor entity with clinical, epidemiologic, genetic, histologic,
prognostic, and treatment differences from smoking- and alcohol-related head and
neck squamous cell carcinoma. This is now well known by the pathology and medical
community. What is not yet widely known is that several emerging variants of HPV
related carcinoma of the head and neck exist apart from the prototypical non
keratinizing morphology. Further, there is currently considerable variation in
methodologies used and clinical scenarios in which to test for HPV-related head
and neck squamous cell carcinoma, and no standard approach has emerged. In this
article, we will review the morphology of prototypical HPV-related squamous cell
carcinoma of the oropharynx and other HPV-related variants of head and neck
carcinoma with an emphasis on their differential diagnosis, grade, and prognosis,
as well as outline the current best practices for testing for HPV in head and
neck carcinomas.
PMID- 28417201
TI - Quantification of dynamic posterior translation in modified bilateral Alexander
views and correlation with clinical and radiological parameters in patients with
acute acromioclavicular joint instability.
AB - INTRODUCTION: Classification of AC-joint instability is based on radiologic
evaluation of anteroposterior (a.p.) stress views of both shoulders, neglecting
the horizontal component of instability. Recent studies have proposed an
association of dynamic posterior translation (DPT) and inferior clinical results.
The purpose of this study was to quantify DPT in modified Alexander views and
correlate it with other radiological and clinical data. MATERIALS AND METHODS:
Thirty-two patients (4 f, 28 m, mean age 34.1) with acute AC-joint dislocation
(16 = RW III, 16 = RW V) underwent radiological examination including bilateral
a.p. stress views with measurement of the coracoclavicular distance (CCD) and
bilateral modified Alexander views with different approaches to quantify DPT
(overlapping area OAAC, overlapping length OLAC). In addition, the Constant
Score, Subjective Shoulder Value, Taft Score (TF), and the Acromioclavicular
Joint Instability Score (ACJI) were obtained. RESULTS: In Rockwood (RW) type III
injuries, a mean CCD of 15.8 (9.8-22.8) mm, OAAC of 50.9 (0-216.6) mm2, and OLAC
of 6.5 (-4.7-17.9) mm were found. RW V patients showed a CCD of 23.1 (13.7-32.0)
mm; OAAC 7.0 (0-92.3) mm2; and OLAC -4.8 (-19.6-9.8) mm. Particularly in RW III
the CCD, OAAC and OLAC revealed significant correlation with the ACJI (r =
0.64/r = 0.72/r = 0.68, p < 0.05) and TF (r = -0.56/r = 0.68/r = 0.51, p < 0.05).
The proposed quantification tools for DPT were found to have a moderate-to-strong
correlation with the score results, especially with AC-joint specific scores. RW
type V injuries had a moderate correlation with clinical parameters (OAAC with
ACJI: r = 0.44, p > 0.05 and OLAC with TF: r = -0.45, p > 0.05). CONCLUSIONS:
Measuring the OLAC is a convenient way for quantifying DPT in modified Alexander
views. It showed significant correlation with clinical scores, indicating the
relevance of DPT in patients with AC-joint injury.
PMID- 28417202
TI - Cardiorespiratory fitness and muscle strength in pancreatic cancer patients.
AB - PURPOSE: Cancer patients frequently experience reduced physical fitness due to
the disease itself as well as treatment-related side effects. However, studies on
physical fitness in pancreatic cancer patients are missing. Therefore, we
assessed cardiorespiratory fitness and muscle strength of pancreatic cancer
patients. METHODS: We included 65 pancreatic cancer patients, mostly after
surgical resection. Cardiorespiratory fitness was assessed using cardiopulmonary
exercise testing (CPET) and 6-min walk test (6MWT). Hand-held dynamometry was
used to evaluate isometric muscle strength. Physical fitness values were compared
to reference values of a healthy population. Associations between
sociodemographic and clinical variables with patients' physical fitness were
analyzed using multiple regression models. RESULTS: Cardiorespiratory fitness
(VO2peak, 20.5 +/- 6.9 ml/min/kg) was significantly lower (-24%) compared to
healthy reference values. In the 6MWT pancreatic cancer patients nearly reached
predicted values (555 vs. 562 m). Maximal voluntary isometric contraction (MVIC)
of the upper (-4.3%) and lower extremities (-13.8%) were significantly lower
compared to reference values. Overall differences were larger in men than those
in women. Participating in regular exercise in the year before diagnosis was
associated with greater VO2peak (p < .05) and MVIC of the knee extensors (p <
.05). CONCLUSIONS: Pancreatic cancer patients had significantly impaired physical
fitness with regard to both cardiorespiratory function and isometric muscle
strength, already in the early treatment phase (median 95 days after surgical
resection). Our findings underline the need to investigate exercise training in
pancreatic cancer patients to counteract the loss of physical fitness.
PMID- 28417204
TI - Injuries to the Chopart joint complex: a current review.
AB - Chopart complex injuries (CCIs) are thought to be uncommon; however, recent
literature states the rate of misdiagnosis to be between 20 and 41%. Chopart
complex injuries are not ankle injuries, with which they are initially confused
due to a similar mechanism of trauma in many cases. Injury to the Chopart complex
commonly affects multiple structures. The key to optimal treatment is a high
index of clinical suspicion combined with timely accurate imaging studies.
Careful diagnostic workup with high-quality radiographs of the foot in neutral
position should be obtained. Computed tomography (CT) and/or magnetic resonance
imaging (MRI) are recommended to accurately assess bone and soft tissue injury.
CCI frequently leads to prolonged swelling, pain and disability. In some cases,
it may result in a posttraumatic flatfoot deformity.
PMID- 28417203
TI - Effects of diet and exercise on weight-related outcomes for breast cancer
survivors and their adult daughters: an analysis of the DAMES trial.
AB - PURPOSE: Few trials have aimed to promote diet and exercise behaviors in both
cancer survivors and their family members and examine their associations with
weight-related outcomes. We conducted a secondary analysis to examine
associations between change in diet and exercise behaviors and weight-related
outcomes for overweight breast cancer survivors and their overweight adult
daughters in the Daughters And MothErS Against Breast Cancer (DAMES) randomized
trial. METHODS: The DAMES trial assessed the impact of two iteratively tailored,
mailed print diet and exercise interventions against standard brochures over a 12
month period. This analysis examined change in diet and exercise behaviors and
weight-related variables from baseline to post-intervention for the 50 breast
cancer survivors and their adult daughters randomized to the intervention arms.
To reduce the potential for type II error in this pilot, p values <0.10 were
considered statistically significant. RESULTS: For mothers, change in diet
quality was uniquely related to change in BMI (beta = -0.12, p = 0.082), weight
(beta = -0.12, p = 0.060), and waist circumference (beta = -0.38, p = 0.001),
whereas change in caloric intake was related to waist circumference (beta = 0.21,
p = 0.002). For daughters, change in caloric intake was related to change in
waist circumference (beta = 0.12, p = 0.055). However, change in diet quality was
not associated with weight-related outcomes in daughters. Additionally, change in
exercise was not associated with weight-related outcomes in mothers or daughters.
CONCLUSIONS: Findings support mail-based and other tailored interventions for
weight loss in this population, with an emphasis on diet quality for breast
cancer survivors and caloric intake for their adult daughters.
PMID- 28417205
TI - An eclosion hormone-like gene participates in the molting process of Palaemonid
shrimp Exopalaemon carinicauda.
AB - Molting behavior is an important physiological process related to metamorphosis,
growth, and reproduction in crustaceans. Previous studies indicated that the
molting process was controlled by 20-hydroxyecdysone (20E) and upstream hormones,
peptides, and environmental factors, which regulate 20E function. Eclosion
hormone (EH) in insect is a kind of neuropeptide that is regulated by 20E and
triggers ecdysis behavior at the end of molting process. However, the function of
eclosion hormone gene during the molting process in crustaceans is still largely
unknown. In the present study, an eclosion hormone-like gene EcEHL was identified
from Exopalaemon carinicauda. The deduced amino acid sequence of EcEHL contained
a signal peptide, a typical eclosion domain, and six conserved cysteine residues
forming three putative disulfide bonds. EcEHL was predominantly expressed in the
epidermis, gill, and eyestalk of shrimp. In situ hybridization analysis showed
that EcEHL transcripts were localized in gill cells and in medulla externa X
organ, medulla terminalis X-organ, sinus gland, and lamina ganglionaris of
eyestalks. During the molting process of shrimp, EcEHL showed the highest
expression level in shrimp at the premolt stage. The expression level of EcEHL in
shrimp at mid premolt stage was up-regulated by injection of exogenous 20E.
Silencing of EcEHL using double-stranded RNA delayed both the molting process and
ecdysis rate of E. carinicauda. Furthermore, injection of exogenous 20E to shrimp
at mid premolt stage (D2) could remarkably speed up the molting process and also
raise the ecdysis rate of E. carinicauda. The results revealed that EcEHL might
participate in the molting process of shrimp and its expression was regulated by
20E. These data will help us to understand the molecular mechanism of molting in
crustacean.
PMID- 28417206
TI - Erratum to: Effect of the addition of nano-sized sodium hexametaphosphate to
fluoride toothpastes on tooth demineralization: an in vitro study.
PMID- 28417207
TI - Impact of food processing on rye product properties and their in vitro digestion.
AB - PURPOSE: Rye products have been reported to elicit postprandial insulin and
glucose responses which may be beneficial for prevention of type-2 diabetes.
However, mechanisms underlying variations in responses related to processing
techniques are not fully understood. METHODS: Five differently processed rye
products (sourdough-fermented bread, fermented and unfermented crispbread,
extrusion-cooked rye, and porridge) and refined wheat bread were characterised.
Two in vitro methods, a dynamic method simulating digestion in the stomach and
small intestine and a static method, simulating conditions in the stomach were
used to determine viscosity development, structural changes and release of
glucose during digestion. RESULTS: Structural and compositional differences
induced by processing influenced product digestion. Gastric disintegration and
digesta particle size were related to characteristics of the starch/protein
matrix, while digesta viscosity was reduced due to fibre degradation during
fermentation. More cohesive boluses were associated with slower glucose release.
Sourdough fermentation increased amylose leakage and appeared to inhibit starch
hydrolysis despite low digesta viscosity and rapid disintegration. CONCLUSIONS:
The net release of glucose during digestion of foods is determined by several
factors which may vary in their importance depending on product specific
properties.
PMID- 28417208
TI - Aesthetic Shoulder Augmentation with Silicone Implants.
AB - BACKGROUND: Men with narrower shoulders may appear less muscular than other men.
Deltoid muscle underdevelopment or atrophy, a condition commonly linked to narrow
shoulder issues, may be associated with congenital deformity, trauma, or
neoplasm. For some people, regular exercise does not effectively develop the
deltoid muscle region. Some people naturally have a smaller build than others.
Even with developed deltoid muscles, these people still appear to be small. The
authors have performed lateral shoulder augmentation with silicone implants for 4
years. Based on their experience, this procedure stands as a reliable solution
for men with narrow shoulders. METHODS: Lateral shoulder augmentation with
silicone implants was developed and used for 81 patients between April 2009 and
April 2013. None of the patients had shoulder deformities except for two patients
(one patient with Poland's syndrome and one patient with Sprengel's deformity).
The implants were placed through a horizontal axillary crease incision in a plane
dissected between the deltoid fascia and muscle. RESULTS: All augmentation or
correction procedures have been met with complete patient approval. Five patients
had minor complications such as hematoma and implement displacement. However, all
these complications were resolved to the satisfaction of the patients.
CONCLUSION: When silicone implants are used to achieve purely aesthetic
improvements, successful shoulder augmentation procedures are observed. LEVEL OF
EVIDENCE IV: This journal requires that authors assign a level of evidence to
each submission to which Evidence-Based Medicine rankings are applicable. This
excludes Review Articles, Book Reviews, and manuscripts that concern Basic
Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors http://www.springer.com/00266 .
PMID- 28417211
TI - Helminth Diversity in Synanthropic Rodents from an Urban Ecosystem.
AB - Richness and diversity of parasites depend on a set of interrelated factors
related to the characteristics of the host, the environment and the parasites
itself. In the City of Buenos Aires, rodent communities vary according to
landscape structure. The goal of this paper was to study the variations of
helminth richness and diversity among invasive rodent species in different
landscape units of the City of Buenos Aires. 73% of the rodents were parasitized
with at least one of the 10 identified helminth species. Each rodent species
presented its own characteristics in terms of richness, diversity and helminth
composition, keeping these characteristics still occupying more than one
landscape unit. The infracommunities with greater diversity corresponded to R.
norvegicus due to its high values of parasitic richness, proportion of infected
hosts and parasite prevalence. Instead, R. rattus and M. musculus
infracommunities had lower diversity since a high percentage of them presented a
unique helminth species. Within the city, the inhabitants of shantytowns would be
the most exposed to zoonotic diseases transmitted by rodents due to high
abundance of rodents harboring a high parasite load, including species like
Hymenolepis nana and H. diminuta, recognized worldwide from a zoonotic aspect.
PMID- 28417212
TI - LALF32-51-E7 therapeutic vaccine induces antitumor immunity against human
papillomavirus type 16 E7-expressing murine tumor metastases in the lungs.
AB - One important goal of cancer immunotherapy is to prevent and treat tumor
metastasis. We have previously reported the significant antitumor effect induced
by the immunization with our human papillomavirus therapeutic protein-based
vaccine (LALF32-51-E7) without adjuvant and admixed with clinically relevant
adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study,
we evaluated the efficacy of the above mentioned vaccine formulations in
controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic
clone named TC-1* and other intravenous injection site less stressful than the
tail vein. We generated a lung metastasis model by injecting TC-1* cells into the
retro-orbital venous sinus and this is the first study describing it. Also, this
is the first study that demonstrates the efficacy of the immunization with LALF32
51-E7 without adjuvant and admixed with VSSP or Al(OH)3 in controlling metastatic
tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be
used to test the efficacy of other immunotherapeutic strategies based on E6/E7
antigens.
PMID- 28417213
TI - Retrospective analysis of cervical corpectomies: implant-related complications of
one- and two-level corpectomies in 45 patients.
AB - Cervical corpectomies are increasingly used to treat degenerative, metastatic,
inflammatory and traumatic multisegmental diseases. The postoperative results are
thought to correlate mainly with the number of resected vertebral bodies. Thus,
the aim of the study was to analyse complications and early outcome of these
procedures to document the implant-related complications in order to set up a
prospective clinical trial. Forty-five patients, who were treated in our
department from 2011 to 2014 and who were available for a minimum follow-up of 1
year, were consecutively included in this retrospective evaluation. The median
age was 61 (+/-11) years with a female to male sex ratio of 19 to 26,
respectively. In these patients, cervical corpectomies (one-, two- and three
level procedures) were performed. The average number of resected levels was 1.2
levels. The intraoperative loss of blood (LOB), the red cell transfusions (rcT),
the length of operation (LOO) and the usage of drains were investigated and
correlated with intra- and postoperative complications. The mean LOO was 244 min
(+/-68) with a mean LOB of 511 ml (+/-531). The overall complication rate was
22.9% (10 patients). Six patients (13.3%) had implant-related complications due
to loosening and toggling of the screws and/or cage subsidence. Two patients
(4.4%) had a postoperative haematoma and another two patients (4.4%) suffered
from neurological deterioration due to an ongoing and severe myelopathic
syndrome. All these patients received revision surgery. The average time from the
first to revision surgery was 90 days. Cervical corpectomies still remain
procedures with a high complication rate mainly represented by implant-related
failures. These implant-related complications range from screw/plate loosening or
toggling to graft dislocation with subsidence and might be associated with
constructs extended to the C7 vertebral body. In our study population, the rate
of implant failure was comparable to the literature, but not obviously correlated
with the number of vertebral bodies resected. This may be attributed to the
different disease entities. Thus, our results support the use of circumferential
approaches for selected instability scenarios (metastatic or inflammatory
diseases, kyphosis, osteoporosis, etc.) of one- and two-level corpectomies.
PMID- 28417214
TI - Neural Processes Associated with Vocabulary and Vowel-Length Differences in a
Dialect: An ERP Study in Pre-literate Children.
AB - Although familiarity with a language impacts how phonology and semantics are
processed at the neural level, little is known how these processes are affected
by familiarity with a dialect. By measuring event-related potentials (ERPs) in
kindergarten children we investigated neural processing related to familiarity
with dialect-specific pronunciation and lexicality of spoken words before
literacy acquisition in school. Children speaking one of two German dialects were
presented with spoken word-picture pairings, in which congruity (or the lack
thereof) was defined by dialect familiarity with pronunciation or vocabulary. In
a dialect-independent control contrast, congruity was defined by audio-visual
semantic (mis)match. Congruity effects and congruity-by-dialect group
interactions in the ERPs were tested by data-driven topographic analyses of
variance (TANOVA) and theory-driven focal analyses. Converging results revealed
similar congruity effects in the N400 and late-positive-complex (LPC) in the
control contrast for both dialect groups. In the dialect-specific vocabulary
contrast, topographies of the N400- and LPC-effects were reversed depending on
familiarity with the presented dialect words. In the dialect-specific
pronunciation contrast, again a topography reversal was found depending on
dialect familiarity, however, only for the LPC. Our data suggest that neural
processing of unfamiliar words, but not pronunciation variants, is characterized
by semantic processing (increased N400-effect). However, both unfamiliar words
and pronunciation variants seem to engage congruity judgment, as indicated by the
LPC-effect. Thus, semantic processing of pronunciation in dialect words seems to
be rather robust against slight alterations in pronunciation, like changes in
vowel duration, while such alterations may still trigger subsequent control
processes.
PMID- 28417215
TI - The atrophy and laterality of the hippocampal subfields in parents with or
without posttraumatic stress disorder who lost their only child in China.
AB - Investigating hippocampal subfields may provide new and important insights into
the pathophysiology of posttraumatic stress disorder (PTSD). However, no study
has examined the hippocampal subfield volume changes in parents with or without
PTSD who had lost their only child and could no longer conceive in China. Fifty
seven parents with PTSD (PTSD+), 11 trauma-exposed parents without PTSD (PTSD-),
and 39 non-traumatized controls were recruited to examine the hippocampal
subfield volumes using magnetic resonance imaging. Correlations of the volumes
with the time since trauma and Clinician-Administered PTSD Scale (CAPS) scores
were investigated in the PTSD+ group. The volumes of the bilateral cornu ammonis
(CA) 2-3, CA4-dentate gyrus (DG), and left subiculum were significantly smaller
in the PTSD+ and PTSD- groups than in the controls, but there were no significant
differences between the PTSD+ and PTSD- groups. Additionally, the left CA2-3 and
CA4-DG volumes reduced more than those on the right side in the PTSD+ and PTSD-
groups. The subfield volumes were not related to the time since trauma and the
CAPS scores in the PTSD+ group. In conclusion, hippocampal subfield volumes
decreased in parents who lost their only child with or without PTSD, and the
volumetric reduction may be independent of PTSD and trauma-related. Moreover, the
hippocampal volume deficits showed laterality that the left side was affected
more than the right, and the hippocampal subfields may show differential
vulnerabilities to trauma/PTSD, with the CA2-3 and CA4-DG subfields more
sensitive than others.
PMID- 28417217
TI - Levels of cystatin C in low- and high-flux hemodialysis in children with end
stage renal disease.
AB - BACKGROUND: Cystatin-C (CyC) is a middle molecule that is freely filtered at the
glomerulus and almost completely reabsorbed by the proximal tubules. The aim of
this study was to evaluate serum CyC and its reduction ratio as a biomarker for
assessing the adequacy of the hemodialysis (HD) sessions in children with end
stage renal disease on maintenance HD. We also compared levels of CyC in patients
on low-flux HD (LFH) and high-flux HD (HFH). METHODS: Forty patients were
included in the study and divided into two groups, with one group (16 patients)
receiving HFH and the other group receiving LFH (24 patients) (high-flux and low
flux polysulfone filters, respectively). Before and after each dialysis session
serum CyC and beta-2-microglobulin (B2M) levels were measured using an ELISA
technique, and routine laboratory tests were performed for each patient. RESULTS:
Pre-dialytic levels of CyC were significantly lower in the patients receiving HFH
than in those receiving LFH (7.33 +/- 1.35 vs. 9.73 +/- 0.93, respectively; p <
0.0001). In the HFH group, post-dialytic levels of serum CyC were significantly
lower than pre-dialytic levels (4.49 +/- 0.71 vs. 7.33 +/- 1.35, respectively; p
< 0.0001). The reduction ratio (RR) of CyC was significantly higher in the HFH
group than in the LFH group (38.2 +/- 3.91 vs. -6.49 +/- 5.05, respectively; p <
0.0001). Serum CyC level significantly correlated with B2M, urea and creatinine
levels in both the LFH and HFH groups, whereas its RR significantly correlated
with the RRs of urea, creatinine, and B2M in the HFH group. CONCLUSION: The
results of our study emphasize the role of CyC as a good marker for assessing the
adequacy of HD sessions in children on HFH and show that the CyC RR may be used
as an index of middle-molecule toxin clearance following HFH sessions.
PMID- 28417219
TI - Treatment effect of methylphenidate on intrinsic functional brain network in
medication-naive ADHD children: A multivariate analysis.
AB - Methylphenidate is a first-line therapeutic option for treating attention
deficit/hyperactivity disorder (ADHD); however, elicited changes on resting-state
functional networks (RSFNs) are not well understood. This study investigated the
treatment effect of methylphenidate using a variety of RSFN analyses and explored
the collaborative influences of treatment-relevant RSFN changes in children with
ADHD. Resting-state functional magnetic resonance imaging was acquired from 20
medication-naive ADHD children before methylphenidate treatment and twelve weeks
later. Changes in large-scale functional connectivity were defined using
independent component analysis with dual regression and graph theoretical
analysis. The amplitude of low frequency fluctuation (ALFF) was measured to
investigate local spontaneous activity alteration. Finally, significant findings
were recruited to random forest regression to identify the feature subset that
best explains symptom improvement. After twelve weeks of methylphenidate
administration, large-scale connectivity was increased between the left fronto
parietal RSFN and the left insula cortex and the right fronto-parietal and the
brainstem, while the clustering coefficient (CC) of the global network and nodes,
the left fronto-parietal, cerebellum, and occipital pole-visual network, were
decreased. ALFF was increased in the bilateral superior parietal cortex and
decreased in the right inferior fronto-temporal area. The subset of the local and
large-scale RSFN changes, including widespread ALFF changes, the CC of the global
network and the cerebellum, could explain the 27.1% variance of the ADHD Rating
Scale and 13.72% of the Conner's Parent Rating Scale. Our multivariate approach
suggests that the neural mechanism of methylphenidate treatment could be
associated with alteration of spontaneous activity in the superior parietal
cortex or widespread brain regions as well as functional segregation of the large
scale intrinsic functional network.
PMID- 28417218
TI - Online support groups for head and neck cancer and health-related quality of
life.
AB - PURPOSE: To investigate the association between using online support groups
(OSGs) and health-related quality of life (HRQoL), and the psychosocial factors
that may influence this association among individuals with head and neck (H&N)
cancer. METHOD: A sample of 199 persons with H&N cancer using four OSGs completed
an online questionnaire using six pre-validated measures for social network, self
efficacy, anxiety and depression, adjustment, empowerment and quality of life. In
addition, socio-demographic as well as illness-related and OSGs-related
information was collected. RESULTS: Participants who had better HRQoL had been
using OSGs for a longer time than those who had worse HRQoL (B = 0.07, p < 0.05).
Depression and adjustment were the only direct mediators in this association,
whereas self-efficacy, anxiety and empowerment appeared as indirect mediators.
CONCLUSION: Participation in OSGs was found to be associated to better HRQoL
either directly or indirectly through decreasing depression, anxiety and the
negative adjustment behaviours and increasing self-efficacy and empowerment of
the users. The study presented a potential model of pathways linking OSG use and
HRQoL for those with H&N cancer. However, the model needs to be tested in future
longitudinal studies and the associations proposed need to be explored in greater
detail.
PMID- 28417220
TI - Synthesis of Naked-eye Detectable Fluorescent 2H-chromen-2-One 2, 6
Dicyanoanilines: Effect of Substituents and pH on Its Luminous Behavior.
AB - A variety of new coumarin derivatives containing C-4 bridged 2,6-dicyanoanilines
(4a-4d) were synthesized via multicomponent one pot approach. These novel sensors
were characterized by spectral analysis and a series of pH sensing fluorescence
studies were performed, the results indicating that the sensors are highly
selective and more effective at various pH. The fluorescence colour changes at
different pH could be directly detected by naked eyes.
PMID- 28417221
TI - Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or
neuromodulators in the enteric nervous system of the porcine esophagus.
AB - Zinc transporter 3 (ZnT3) is one of the zinc transporters family. It is closely
connected to the nervous system, where enables the transport of zinc ions from
the cytoplasm to synaptic vesicles. This substance has been described within the
central and peripheral nervous system, especially in the enteric nervous system
(ENS). The aim of the present study was to describe the co-localization of ZnT3
with selected neuromediators and/or neuromodulators participating in sensory
stimuli conduction in neurons of the ENS within the porcine esophagus. Co
localization of ZnT3 with substance P (SP), leucine enkephalin (LENK) and
calcitonin gene-related peptide (CGRP) was studied using standard double
immunofluorescence technique. The obtained results show that ZnT3, SP and/or LENK
may occur in the same enteric neurons, and the degree of co-localization of these
substances clearly depends on the fragment of esophagus studied and the type of
enteric ganglia. In contrast, the co-localization of ZnT3 with CGRP was not
observed during the present investigation. The obtained results suggest that ZnT3
in the ENS may be involved in the conduction of sensory and/or pain stimuli.
PMID- 28417223
TI - Dorsal metacarpal veins: anatomic variation and potential clinical implications.
AB - The dorsal metacarpal veins are frequently cannulated. Cannulation success is
determined by several variable anatomic features. The objective of this study is
to classify, for the first time, the anatomic variants of the dorsal metacarpal
veins. In this cross-sectional study, 520 university students and staff were
conveniently recruited. The dorsal metacarpal veins in 1040 hands were studied.
Venous visibility was enhanced by either tourniquet application or near-infrared
illumination. Variant patterns of the dorsal metacarpal veins were classified.
The final analysis included 726 hands, for an exclusion rate of 30 %. Eight
pattern types were identified. Three anatomic features informed the variation.
Bilateral symmetry of the dorsal metacarpal veins was present in 352 participants
(83 % of the total). The overall frequency distribution of variants in both hands
was similar (P = 0.8). The frequency distribution of variants was subject to
sexual dimorphism (P = 0.001), ethnic variation (P < 0.001), and technical
variation (P < 0.001). The anatomic variants of the dorsal metacarpal veins were
sorted into decreasingly frequent primary, secondary, and tertiary groups. The
groups may signify a progressive increase in difficulty of peripheral
cannulation, in the mentioned order. As such, primary patterns are the most
common and likely the easiest to cannulate, while tertiary patterns are the least
common and likely the most difficult to cannulate. The preceding premise, in
tandem with the bilateral asymmetry of the veins, is clinically significant. With
cannulation difficulty likely signifying an underlying tertiary pattern, the
contralateral dorsal metacarpal veins are probabilistically characterized by a
primary pattern and are, as such, the easier option for peripheral venous
cannulation.
PMID- 28417224
TI - Erratum to: Glutamate and alpha-ketoglutarate: key players in glioma metabolism.
PMID- 28417222
TI - Role of FOXO transcription factors in crosstalk between mitochondria and the
nucleus.
AB - FOXO transcription factors are evolutionally conserved regulators of organismal
life span downstream of insulin signaling. After integrating cellular signals
from various stimuli such as growth factors, oxidative stress, and energy
deprivation, FOXO factors induce expression of a specific set of genes that
regulate various cellular processes to maintain homeostasis at a cellular or
organismal level. In this review, we discuss roles of FOXO proteins in the
maintenance of mitochondria, organelles critical for cellular quality control.
FOXO factors protect mitochondria by activating mitochondrial antioxidant enzymes
and they help remodel damaged mitochondria by inducing remodeling processes such
as mitophagy. Furthermore, we also review the recently identified FOXO-dependent
retrograde signaling from stressed mitochondria to the nucleus, which suggest
that FOXO mediates the crosstalk between these two important organelles to
maintain cell homeostasis. In addition, we introduce a mitohormetic role of
gamitrinib-triphenylphosphonium (G-TPP), a mitochondrial heat shock protein (Hsp)
inhibitor that can induce mild mitochondrial stress to protect cells from future
insults in a FOXO-dependent manner.
PMID- 28417216
TI - Pathogenic mechanisms following ischemic stroke.
AB - Stroke is the second most common cause of death and the leading cause of
disability worldwide. Brain injury following stroke results from a complex series
of pathophysiological events including excitotoxicity, oxidative and nitrative
stress, inflammation, and apoptosis. Moreover, there is a mechanistic link
between brain ischemia, innate and adaptive immune cells, intracranial
atherosclerosis, and also the gut microbiota in modifying the cerebral responses
to ischemic insult. There are very few treatments for stroke injuries, partly
owing to an incomplete understanding of the diverse cellular and molecular
changes that occur following ischemic stroke and that are responsible for
neuronal death. Experimental discoveries have begun to define the cellular and
molecular mechanisms involved in stroke injury, leading to the development of
numerous agents that target various injury pathways. In the present article, we
review the underlying pathophysiology of ischemic stroke and reveal the
intertwined pathways that are promising therapeutic targets.
PMID- 28417225
TI - Comparative proteomic analysis provides insight into 10-hydroxy-2-decenoic acid
biosynthesis in honey bee workers.
AB - 10-Hydroxy-2-decenoic acid (10-HDA) is the major compound produced from the
mandibular glands (MGs) of honey bee workers. However, little information is
available on the molecular mechanisms of 10-HDA biosynthesis. In our study, based
on investigating the 10-HDA secretion pattern and the morphological
characteristics of MGs from honey bee workers of different ages, a comparative
proteomic analysis was performed in the MGs of workers with different 10-HDA
production. In total, 59 up-regulated protein species representing 45 unique
proteins were identified in high 10-HDA-producing workers by 2-DE-MALDI-TOF/TOF
MS. These proteins were involved in carbohydrate/energy metabolism, fatty acid
metabolism, protein metabolism and folding, antioxidation, cytoskeleton,
development and cell signaling. Proteins related to fatty acid metabolism,
including fatty acid synthase and beta-oxidation enzymes, are potentially crucial
proteins involved in 10-HDA biosynthesis pathway. And RNA interference (RNAi)
results demonstrated that knockdown of electron transfer flavoprotein subunit
beta (ETF-beta), one of the protein related to fatty acid metabolism, decreased
10-HDA production of worker bees, suggesting that ETF-beta was necessary for 10
HDA biosynthesis. This study reveals the characteristics of MGs of worker bees at
different developmental stages and proteins associated with 10-HDA biosynthesis,
which provides the first insight into the molecular mechanism of 10-HDA
biosynthesis.
PMID- 28417226
TI - The repertoire of bitter taste receptor genes in canids.
AB - Bitter taste receptors (Tas2rs) play important roles in mammalian defense
mechanisms by helping animals detect and avoid toxins in food. Although Tas2r
genes have been widely studied in several mammals, minimal research has been
performed in canids. To analyze the genetic basis of Tas2r genes in canids, we
first identified Tas2r genes in the wolf, maned wolf, red fox, corsac fox,
Tibetan fox, fennec fox, dhole and African hunting dog. A total of 183 Tas2r
genes, consisting of 118 intact genes, 6 partial genes and 59 pseudogenes, were
detected. Differences in the pseudogenes were observed among nine canid species.
For example, Tas2r4 was a pseudogene in the dog but might play a functional role
in other canid species. The Tas2r42 and Tas2r10 genes were pseudogenes in the
maned wolf and dhole, respectively, and the Tas2r5 and Tas2r34 genes were
pseudogenes in the African hunting dog; however, these genes were intact genes in
other canid species. The differences in Tas2r pseudogenes among canids might
suggest that the loss of intact Tas2r genes in canid species is species
dependent. We further compared the 183 Tas2r genes identified in this study with
Tas2r genes from ten additional carnivorous species to evaluate the potential
influence of diet on the evolution of the Tas2r gene repertoire. Phylogenetic
analysis revealed that most of the Tas2r genes from the 18 species intermingled
across the tree, suggesting that Tas2r genes are conserved among carnivores.
Within canids, we found that some Tas2r genes corresponded to the traditional
taxonomic groupings, while some did not. PIC analysis showed that the number of
Tas2r genes in carnivores exhibited no positive correlation with diet
composition, which might be due to the limited number of carnivores included in
our study.
PMID- 28417227
TI - Intestinal Pseudo-Obstruction as the Presenting Manifestation of Kawasaki
Disease.
PMID- 28417228
TI - A Penalized Likelihood Method for Structural Equation Modeling.
AB - A penalized likelihood (PL) method for structural equation modeling (SEM) was
proposed as a methodology for exploring the underlying relations among both
observed and latent variables. Compared to the usual likelihood method, PL
includes a penalty term to control the complexity of the hypothesized model. When
the penalty level is appropriately chosen, the PL can yield an SEM model that
balances the model goodness-of-fit and model complexity. In addition, the PL
results in a sparse estimate that enhances the interpretability of the final
model. The proposed method is especially useful when limited substantive
knowledge is available for model specifications. The PL method can be also
understood as a methodology that links the traditional SEM to the exploratory SEM
(Asparouhov & Muthen in Struct Equ Model Multidiscipl J 16:397-438, 2009). An
expectation-conditional maximization algorithm was developed to maximize the PL
criterion. The asymptotic properties of the proposed PL were also derived. The
performance of PL was evaluated through a numerical experiment, and two real data
illustrations were presented to demonstrate its utility in psychological
research.
PMID- 28417229
TI - A research agenda for the European Association for Endoscopic Surgeons (EAES).
AB - INTRODUCTION: The European Association of Endoscopic Surgeons (EAES) conducted
this study aiming to identify the top research questions which are relevant to
surgeons in Minimal Access Surgery (MAS). This is in order to promote and link
research questions to the current clinical practice in MAS in Europe. METHODS:
Using a systematic methodology, (modified Delphi), the EAES members and
leadership teams were surveyed to obtain consensus on the top research priorities
in MAS. The responses were categorized and redistributed to the membership to
rate the level of importance of each research question. The data were reported as
the weighted average score with a scale from 1 (lowest agreement) to 5 (highest
agreement). RESULTS: In total, 324 of 2580 (12.5%) of the EAES members and the
leaders responded to the survey and contributed to the final consensus. The
ranked responses over the 80th percentile identified 39 research priorities with
rating ranged from 4.22 to 3.67. The top five highest ranking research priorities
in the EAES were centered on improving training in MAS, laparoscopic surgery for
benign upper gastrointestinal conditions, integration of novel technology in OR,
translational and basic science research in bariatric surgery and investigating
the role of MAS in rectal cancer. CONCLUSION: An EAES research agenda was
developed using a systematic methodology and can be used to focus MAS research.
This study was commissioned by the European Association for Endoscopic Surgery
(EAES).
PMID- 28417230
TI - Retraction Note To: VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and
Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway.
PMID- 28417231
TI - High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.
AB - Lipid composition determines membrane properties, and cholesterol plays a major
role in this determination as it regulates membrane fluidity and permeability, as
well as induces the formation of coexisting phases and domains in the membrane.
Biological membranes display a very diverse lipid composition, the lateral
organization of which plays a crucial role in regulating a variety of membrane
functions. We hypothesize that, during biological evolution, membranes with a
particular cholesterol content were selected to perform certain functions in the
cells of eukaryotic organisms. In this review, we discuss the major membrane
properties induced by cholesterol, and their relationship to certain membrane
functions.
PMID- 28417232
TI - Healthy cortical development through adolescence and early adulthood.
AB - Adolescence is a period of significant brain changes; however, the effects of age
and sex on cortical development are yet to be fully characterized. Here, we
utilized innovative intrinsic curvature (IC) analysis, along with the traditional
cortical measures [cortical thickness (CT), local gyrification index (LGI), and
surface area (SA)], to investigate how these indices (1) relate to each other and
(2) depend on age and sex in adolescent cortical development. T1-weighted
magnetic resonance images from 218 healthy volunteers (age range 8.3-29.2 years,
M[SD] = 16.5[3.4]) were collected at two sites and processed with FreeSurfer and
Caret software packages. Surface indices were extracted per cortex area (frontal,
parietal, occipital, temporal, insula, and cingulate). Correlation analyses
between the surface indices were conducted and age curves were modelled using
generalized additive mixed-effect models. IC showed region-specific associations
with LGI, SA, and CT, as did CT with LGI. SA was positively associated with LGI
in all regions and CT in none. CT and LGI, but not SA, were inversely associated
with age in all regions. IC was inversely associated with age in all but the
occipital region. For all regions, males had larger cortical SA than females.
Males also had larger LGI in all regions and larger IC of the frontal area;
however, these effects were accounted for by sex differences in SA. There were no
age-by-sex interactions. The study of IC adds a semi-independent, sensitive
measure of cortical morphology that relates to the underlying cytoarchitecture
and may aid understanding of normal brain development and deviations from it.
PMID- 28417233
TI - A posterior-to-anterior shift of brain functional dynamics in aging.
AB - Convergent evidence from task-based functional magnetic resonance imaging (fMRI)
studies suggests a posterior-to-anterior shift as an adaptive compensatory
scaffolding mechanism for aging. This study aimed to investigate whether brain
functional dynamics at rest follow the same scaffolding mechanism for aging using
a large Chinese sample aged from 22 to 79 years (n = 277). We defined a
probability of brain regions being hubs over a period of time to characterize
functional hub dynamic, and defined variability of the functional connectivity to
characterize dynamic functional connectivity using resting-state fMRI. Our
results revealed that both functional hub dynamics and dynamic functional
connectivity posited an age-related posterior-to-anterior shift. Specifically,
the posterior brain region showed attenuated dynamics, while the anterior brain
regions showed augmented dynamics in aging. Interestingly, our analysis further
indicated that the age-related episodic memory decline was associated with the
age-related decrease in the brain functional dynamics of the posterior regions.
Hence, these findings provided a new dimension to view the scaffolding mechanism
for aging based on the brain functional dynamics.
PMID- 28417235
TI - Letter to the Editor concerning "Rehydration of a degenerated disc on MRI
synchronized with transition of Modic changes following stand-alone XLIF" by K.
Kita, T. Sakai, M. Abe, Y. Takata and K. Sairyo (Eur Spine J; 2017.
doi:10.1007/s00586-017-4945-6).
PMID- 28417234
TI - Central lumbar spinal stenosis: natural history of non-surgical patients.
AB - PURPOSE: The aim of the present study was to examine the natural history in
patients with lumbar spinal stenosis. The incidence of surgery for this condition
has increased considerably during the past decades in spite of a fairly favorable
natural history in previous studies. METHODS: 146 consecutive patients with
clinical signs and image findings of lumbar spinal stenosis, who were not
recommended surgical treatment, were followed; the reason as to why surgery was
not recommended was a moderate symptom level. The follow-up rate was 89% after
3.3 years. Group values for comorbidities and diagnostic imaging were comparable
to patients selected for surgery, with the exception of a lower frequency of
degenerative spondylolisthesis among the non-operative patients. The mean age of
those observed was 68 (21-91), and 58% were females. RESULTS: During the
observation period spontaneous improvements were found for pain and health
related quality of life, but not for walking. Using the minimum clinically
important difference for VAS, leg and back pain improved in 32 and 36% of
patients, respectively, were unchanged in 55 and 54%, and worsened in 13 and 10%.
Findings on diagnostic imaging did not influence patient outcome, except for
stenoses with cross-sectional area <0.5 cm2 where spontaneous improvement was not
seen. Revision of the decision not to operate occurred in 10 cases (7%).
CONCLUSIONS: The natural history of LSS with moderate symptom levels rarely shows
symptom deterioration over a median of 3.3 years; in fact, a slight improvement
of symptoms was seen at group levels. The treatment decision was revised for 7%,
and for the rest an increase in pain was seen in 10-13%. The results support
reluctance towards surgery, if the symptom levels are tolerable for the patients.
PMID- 28417238
TI - Bilateral Mastectomy as Overtreatment for Breast Cancer in Women Age Forty Years
and Younger with Unilateral Operable Invasive Breast Cancer.
AB - BACKGROUND: Young women with breast cancer (BC) have an increased risk of
contralateral breast cancer (CBC) compared with older women. This may contribute
to the rising rates of bilateral mastectomy (BM), but it is unclear if BM leads
to improved outcomes. METHODS: A prospectively maintained database was reviewed.
Patient and tumor characteristics, survival, and rate of CBC were compared in
women age <=40 years treated for unilateral Stage 1-3 BC from January 2000
through December 2013. RESULTS: Patients ranged in age from 20 to 40 (mean 36)
years. Of the 446 women, 188 had breast conservation surgery (BCS), 78 had
unilateral mastectomy (UM), and 183 had BM. UM, BCS, and BM groups did not differ
in mean age, tumor type, hormone receptor status, or Her2 status. Patients in the
BCS and BM group had smaller, fewer node-positive (p = 0.02) and lower grade
tumors (p < 0.01) compared with the UM group. With a median follow-up of 79
months, Disease-free survival was similar for patients treated with BM, BCS (p =
0.22), or UM (p = 0.75). OS was significantly worse in the patients treated with
UM (0.02) but was not different between the BCS and BM groups. CBC incidence was
2% (5/263) in patients who underwent BCS or UM, and 0.4% (1/244) in patients
without a germline genetic mutation. CONCLUSIONS: BCS and UM resulted in similar
disease-free survival (DFS) as BM in patients age 40 years and younger with BC.
BCS and BM had similar OS, whereas UM patients had worse OS. Invasive CBC
incidence was less than 0.5% at 10 years in patients without identified germline
genetic mutations.
PMID- 28417237
TI - Assessment of satisfaction based on age and gender in functional and aesthetic
rhinoplasty.
AB - The aim of this study was to assess patients' satisfaction based on gender and
age using the Rhinoplasty Outcomes Evaluation (ROE) post-rhinoplasty from both
functional and aesthetic outcomes. The study design was a prospective
observational study. A total of 103 patients who underwent Rhinoplasty were
prospectively investigated from January 2011 through December 2013 at King
Abdulaziz University Hospital in Riyadh, Saudi Arabia. The sample included 61
males (59.2%) and 42 females (40.7%). The overall mean age was (25.2 +/- 5.9)
years (range 17-48 years). ROE was distributed pre- and post-surgery. The overall
difference in satisfaction was significant (p < 0.0001). The mean satisfaction
difference of function was increased by 21.5%, raising the satisfaction
percentage from 57.1% initially to 78.5% post-surgery (mean -0.215, CI -0.269,
0.161). Satisfaction of shape post-rhinoplasty showed that the mean satisfaction
increased by 31.3% (mean -0.313, CI -0.369, -0.256), which changed the
satisfaction from a mean of 44.2% before surgery to 75.5% post-rhinoplasty (p =
0.000). There was no significant difference in satisfaction between males and
females, nor was there a significant difference in satisfaction among different
age groups (p > 0.05). There was a significant overall increase in patients'
satisfaction from functional and aesthetic outcomes post-surgery based on ROE.
Our study showed that age and gender did not significantly affect satisfaction.
The ROE was a useful tool to implement for assessing the quality-of-life post
rhinoplasty.
PMID- 28417239
TI - Incidental Gallbladder Cancer: Residual Cancer Discovered at Oncologic Extended
Resection Determines Outcome: A Report from High- and Low-Incidence Countries.
AB - BACKGROUND: Gallbladder cancer detected incidentally after cholecystectomy (IGBC)
currently is the most common diagnosis of gallbladder cancer, and oncologic
extended resection (OER) is recommended for tumors classified higher than T1b.
However, the precise prognostic significance of residual cancer (RC) found at the
time of OER has not been well established. This analysis aimed to determine the
prognostic impact of RC found in patients with IGBC undergoing OER. METHODS:
Outcomes for IGBC at a center for a low-incidence country (USA) and a high
incidence country (Chile) between January 1999 and June 2015 were analyzed.
Residual cancer was defined as histologically proven cancer at OER. Predictors of
disease-specific survival (DSS) were analyzed. RESULTS: Of 187 patients, 171
(91.4%) achieved complete resection (R0) at OER. The rates of surgical mortality
and severe morbidity were respectively 1.1 and 9.6%. Of the 187 patients, 73
(39%) had RC. Perineural invasion and/or lymphovascular invasion and T3 stage
were associated with the presence of RC. In both countries, RC was associated
with a significantly shorter median survival (23% vs not reached; p < 0.001) and
lower 5-year DSS rate (19% vs. 74%; p < 0.001) despite R0 resection. In the
multivariable analysis, RC was an independent poor predictor of DSS (hazard ratio
[HR], 4.00; 95% confidence interval [CI], 2.13-7.47; p < 0.001), as were
lymphovascular and/or perineural invasion (HR, 1.95; 95% CI, 1.19-3.21; p =
0.008). CONCLUSIONS: The presence of RC in patients undergoing OER for IGBC is
associated with poor DSS in both high- and low-incidence countries, even when R0
resection is achieved. Residual cancer defines a high-risk cohort for whom
adjuvant therapy may be beneficial.
PMID- 28417240
TI - Development and Validation of the Pretending Orgasm Reasons Measure.
AB - Pretending orgasm is a widespread phenomenon, reported by both men and women. We
report here on the development of a new measure to assess reasons for pretending.
In three studies, using large diverse samples, we obtained a comprehensive list
of reasons for pretending orgasms (Study 1; N = 46) and conducted both
exploratory (Study 2; N = 416) and confirmatory (Study 3; N = 1010) factor
analyses identifying six reasons for pretending an orgasm: feels good, for
partner, not into sex, manipulation/power, insecurity, and emotional
communication. Sexual dysfunction was correlated with frequency of pretending
orgasms for reasons such as insecure, not into sex, for partner, and emotional
communication. Usefulness for future research and clinical implications are
discussed.
PMID- 28417241
TI - Use of Tumor Necrosis Factor Alpha Inhibitors for Inflammatory Bowel Disease
Patients with Concurrent Heart Failure.
AB - BACKGROUND: Prescribing information for tumor necrosis factor alpha (TNFalpha)
inhibitors, a mainstay of treatment for moderate to severe inflammatory bowel
disease (IBD), instructs cautious use in those with heart failure (HF). However,
the limited data behind these warnings are inconclusive and should be weighed
against mounting evidence demonstrating worse cardiac outcomes in active IBD.
AIMS: To assess whether TNFalpha inhibitor use is reduced in patients with IBD
and HF by analyzing physician practice and prescription patterns. METHODS: Using
a Stanford University database, we queried TNFalpha inhibitor prescriptions in
8905 patients with an ICD-9 diagnosis of Crohn's disease or ulcerative colitis.
Detailed chart review analysis was done for patients with a concurrent diagnosis
of HF who were prescribed anti-TNFalpha agents. In addition, we collected survey
data from 25 gastroenterologists on their usage of these drugs for patients with
IBD and HF. RESULTS: TNFalpha inhibitors were prescribed to 10/455 (2.2%) IBD
patients with HF compared to 1265/8450 (15.0%) in IBD patients without HF (p <
0.0001). Of those ten with HF prescribed TNFalpha inhibitors, only one had it
discontinued because of HF exacerbation while on drug. Survey data indicated few
(5/25) providers do not actively avoid TNFalpha inhibitors for those with HF.
CONCLUSIONS: IBD patients with HF are prescribed significantly less TNFalpha
inhibitors than those without HF. The majority of providers are either uncertain
about or actively avoid use of anti-TNFalpha medications for those with HF. The
risks and benefits of anti-TNFalpha use in HF patients must be investigated
further.
PMID- 28417242
TI - Combined use of the multidimensional prognostic index (MPI) and procalcitonin
serum levels in predicting 1-month mortality risk in older patients hospitalized
with community-acquired pneumonia (CAP): a prospective study.
AB - BACKGROUND: Several scores and biomarkers, i.e., procalcitonin (PCT), were
proposed to stratify the mortality risk in community-acquired pneumonia (CAP).
AIM: Evaluating prognostic accuracy of PCT and Multidimensional Prognostic Index
(MPI) for 1-month mortality risk in older patients with CAP. METHODS: At hospital
admission and at discharge, patients were evaluated by a Comprehensive Geriatric
Assessment to calculate MPI. Serum PCT was measured at admission and 1, 3, and 5
days after hospital admission. RESULTS: 49 patients were enrolled. The overall 1
month mortality was 44.5 for 100-persons year. Mortality rates were higher with
the increasing of MPI. In survived patients, MPI at discharge showed higher
predictive accuracy than MPI at admission. Adding PCT levels to admission MPI
prognostic accuracy for 1-month mortality significantly increased. CONCLUSION: In
older patients with CAP, MPI significantly predicted 1 month mortality. PCT
levels significantly improved the accuracy of MPI at admission in predicting 1
month mortality.
PMID- 28417243
TI - Criterion-related validity of self-reported stair climbing in older adults.
AB - INTRODUCTION: Stair climbing is an activity of daily living that might contribute
to increase levels of physical activity (PA). To date, there is no study
examining the validity of climbing stairs assessed by self-report. The aim of
this study was, therefore, to examine the validity of estimated stair climbing
from one question included in a common questionnaire compared to a pattern
recognition activity monitor in older adults. METHODS: A total of 138 older
adults (94 women), aged 65-86 years (70.9 +/- 4.7 years), from the IMPACT65 +
study participated in this validity study. Estimates of stair climbing were
obtained from the European Prospective Investigation into Cancer and Nutrition
(EPIC) PA questionnaire. An objective assessment of stair climbing was obtained
with the Intelligent Device for Energy Expenditure and Activity (IDEEA) monitor.
RESULTS: The correlation between both methods to assess stair climbing was fair
(rho = 0.22, p = 0.008 for PA energy expenditure and rho = 0.26, p = 0.002 for
duration). Mean differences between self-report and the IDEEA were 7.96 +/- 10.52
vs. 9.88 +/- 3.32 METs-min/day for PA energy expenditure, and 0.99 +/- 1.32 vs.
1.79 +/- 2.02 min/day for duration (both Wilcoxon test p < 0.001). Results from
the Bland-Altman analysis indicate that bias between both instruments were -1.91
+/- 10.30 METs-min/day and -0.80 +/- 1.99 min/day, and corresponding limits of
agreement for the two instruments were from 18.27 to -22.10 METs-min/day and from
3.09 to -4.70 min/day, respectively. CONCLUSION: Our results indicate that self
reported stair climbing has modest validity to accurately rank old age
participants, and underestimates both PAEE and its duration, as compared with an
objectively measured method.
PMID- 28417244
TI - Ribociclib: First Global Approval.
AB - Ribociclib is an oral, small-molecule inhibitor of cyclin-dependent kinase (CDK)
4 and 6 that is under development by Novartis for the treatment of cancer. CDKs
play an important role in cell cycle progression and cellular proliferation, and
inhibition of these kinases with ribociclib results in G1 phase cell-cycle
arrest. Ribociclib, in combination with an aromatase inhibitor, was recently
approved in the USA for the first-line treatment of advanced breast cancer and
has been submitted for approval in the EU for this indication. Ribociclib is
undergoing further phase III investigations in breast cancer and is being
evaluated in phase I or II trials for various solid tumour types and
haematological malignancies. This article summarizes the milestones in the
development of ribociclib leading to this first global approval for use as
initial endocrine-based therapy for the treatment of postmenopausal women with
hormone receptor-positive, human epidermal growth factor receptor 2-negative
advanced or metastatic breast cancer.
PMID- 28417245
TI - Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4.
AB - A fixed-dose combination tablet comprising the hepatitis C virus (HCV) NS5A
inhibitor elbasvir and the HCV NS3/4A protease inhibitor grazoprevir
(elbasvir/grazoprevir; ZepatierTM) was recently approved for the treatment of
chronic HCV genotype 1 and 4 infection in the EU and the USA. In phase III
trials, 12 or 16 weeks of treatment with once-daily elbasvir/grazoprevir (fixed
dose tablet or as individual agents), taken with or without ribavirin, generally
provided high rates of sustained virological response at 12 weeks (SVR12) in
treatment-naive and -experienced adult patients with chronic HCV genotype 1a, 1b
or 4 infection, including those with or without compensated cirrhosis, HIV co
infection, inherited blood disorders or chronic kidney disease or patients
receiving opioid agonist therapy or of Japanese origin. Elbasvir/grazoprevir was
generally well tolerated. Thus, elbasvir/grazoprevir, with or without ribavirin,
represents an effective new option for the treatment of adults with chronic HCV
genotype 1 and 4 infection, including a number of difficult-to-treat populations.
PMID- 28417247
TI - Influence of environmental temperature and humidity on questing ticks in central
Spain.
AB - Ticks are important ectoparasites and vectors of the pathogens that cause disease
in humans and animals. At a natural reserve in Ciudad Real (Spain), an
uncontrollable infestation of wild animals with Hyalomma lusitanicum (Koch) has
been reported by some game reserve owners. Many questions about distribution,
abundance, and phenology of this tick in this area remain unanswered. The aim of
this study was to determine if temperature and relative humidity affect the
questing tick's activity in four species of ticks in a meso-Mediterranean area,
especially that of H. lusitanicum. Data for tick populations in six selected
sampling sites every month, between January 2007 and December 2013 were used.
Temperature and humidity values (ground and environmental) were recorded. The
sampling effort, the similarity between sites, and the phenology of the species
were analyzed. Effects of environmental variables on tick's activity were
assessed by general linear models (GLM) whereas the comparative importance of
variables was measured by hierarchical variance partitioning. Hyalomma
lusitanicum represented 96.3% of the four species of ticks collected. Spring and
summer months presented a higher activity of ticks, than autumn and winter
months. In general, humidity variables were negatively related to the activity of
ticks, whereas temperature variables were positively related. Our results suggest
that the highest activity in the area is produced by biological characteristics
of H. lusitanicum; being temperature and humidity the most important
environmental factors influencing the abundance of this species in the region.
PMID- 28417246
TI - Mammalian target of rapamycin (mTOR) as a potential therapeutic target in various
diseases.
AB - Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that
belongs to Phosphatidylinositol-3-kinase related kinase superfamily. The
signaling pathways of mTOR are integrated through the protein complexes of mTORC1
and mTORC2. mTORC1 controls protein synthesis, cell growth, proliferation,
autophagy, cell metabolism, and stress responses, whereas mTORC2 seems to
regulate cell survival and polarity. Dysregulation of the mTOR pathway has been
implicated in the pathophysiology of a number of disease conditions, including
cancer, cardiovascular, neurodegenerative, and various renal diseases. The
hyperactivation of the mTOR pathway leads to increase in cell growth and
proliferation and also has been documented to stimulate tumor growth. Therefore,
investigation of the involvement of mTOR and its downstream pathways in various
diseases intensively preoccupied scientific community. The present review is
focussed on recent advances in the understanding of the mTOR signaling pathway
and its role in health and various diseases.
PMID- 28417248
TI - Ticks and tick-borne pathogens of dogs along an elevational and land-use gradient
in Chiriqui province, Panama.
AB - Systematic acarological surveys are useful tools in assessing risk to tick-borne
infections, especially in areas where consistent clinical surveillance for tick
borne disease is lacking. Our goal was to identify environmental predictors of
tick burdens on dogs and tick-borne infectious agents in dog-derived ticks in the
Chiriqui Province of western Panama to draw inferences about spatio-temporal
variation in human risk to tick-borne diseases. We used a model-selection
approach to test the relative importance of elevation, human population size,
vegetative cover, and change in landuse on patterns of tick parasitism on dogs.
We collected 2074 ticks, representing four species (Rhipicephalus sanguineus, R.
microplus, Amblyomma ovale, and Ixodes boliviensis) from 355 dogs. Tick
prevalence ranged from 0 to 74% among the sites we sampled, and abundance ranged
from 0 to 20.4 ticks per dog with R. sanguineus s.l. being the most commonly
detected tick species (97% of all ticks sampled). Whereas elevation was the best
single determinant of tick prevalence and abundance on dogs, the top models also
included predictor variables describing vegetation cover and landuse change.
Specifically, low-elevation areas associated with decreasing vegetative cover
were associated with highest tick occurrence on dogs, potentially because of the
affinity of R. sanguineus for human dwellings. Although we found low prevalence
of tick-borne pathogen genera (two Rickettsia-positive ticks, no R. rickettsia or
Ehrlichia spp.) in our study, all of the tick species we collected from dogs are
known vectors of zoonotic pathogens. In areas where epidemiological surveillance
infrastructure is limited, field-based assessments of acarological risk can be
useful and cost-effective tools in efforts to identify high-risk environments for
tick-transmitted pathogens.
PMID- 28417249
TI - Virus-vector relationship in the Citrus leprosis pathosystem.
AB - Citrus leprosis has been one of the most destructive diseases of citrus in the
Americas. In the last decade important progress has been achieved such as the
complete genome sequencing of its main causal agent, Citrus leprosis virus C
(CiLV-C), belonging to a new genus Cilevirus. It is transmitted by Brevipalpus
yothersi Baker (Acari: Tenuipalpidae), and is characterized by the localized
symptoms it induces on the leaves, fruits and stems. It occurs in the American
continents from Mexico to Argentina. The virus was until recently considered
restricted to Citrus spp. However, it was found naturally infecting other plants
species as Swinglea glutinosa Merrill and Commelina benghalensis L., and has been
experimentally transmitted by B. yothersi to a large number of plant species.
Despite these advances little is known about the virus-vector relationship that
is a key to understanding the epidemiology of the disease. Some components of the
CiLV-C/B. yothersi relationship were determined using the common bean (Phaseolus
vulgaris L. cv. 'IAC Una') as a test plant. They included: (a) the virus
acquisition access period was 4 h; (b) the virus inoculation access period was 2
h; (c) the latent period between acquisition and inoculation was 7 h; (d) the
period of retention of the virus by a single viruliferous mite was at least 12
days; (d) the percentage of viruliferous individuals from mite colonies on
infected tissues ranged from 25 to 60%. The experiments confirmed previous data
that all developmental stages of B. yothersi (larva, protonymph and deutonymph,
adult female and male) were able to transmit CiLV-C and that transovarial
transmission of the virus did not occur. CiLV-C can be acquired from lesions on
leaves, fruits and stems by B. yothersi. Based on the distribution of lesions
produced by single viruliferous B. yothersi on bean leaves, it is concluded that
they tend to feed in restricted areas, usually near the veins. The short latent
and transmission periods during the larval stage suggest that the CiLV-C/B.
yothersi relationship is of the persistent circulative type.
PMID- 28417250
TI - Impact of surface roughness on Dielectrophoretically assisted concentration of
microorganisms over PCB based platforms.
AB - This article presents a PCB based microfluidic platform for performing a
dielectrophoretic capture of live microorganisms over inter-digitated electrodes
buried under layers of different surface roughness values. Although
dielectrophoresis has been extensively studied earlier over silicon and polymer
surfaces with printed electrodes the issue of surface roughness particularly in
case of buried electrodes has been seldom investigated. We have addressed this
issue through a layer of spin coated PDMS (of various surface roughness) that is
used to cover the printed electrodes over a printed circuit board. The roughness
in the PDMS layer is generally defined by the roughness of the FR4 base which
houses the printed electrodes as well as other structures. Possibilities arising
out of COMSOL simulations have been well validated experimentally in this work.
PMID- 28417251
TI - Irreversible electroporation for the treatment of rabbit VX2 breast cancer.
AB - Irreversible electroporation (IRE) is considered predominantly as a non-thermal
ablative technique that uses electrical fields to permeabilize cell membranes and
lead to cell death. In this study, we evaluated the efficacy of IRE in the rabbit
VX2 breast cancer model. Thirty-five female New Zealand white rabbits were
inoculated against VX2 breast cancer cells. The rabbits were randomly divided
into two groups: a control group of 15 rabbits and an IRE treatment group of 20
rabbits. Treatment and treatment outcome were evaluated by computerized
tomography (CT) scan (plain or contrast enhanced), tumor growth curves and
pathological examination including H&E, TUNEL, PCNA and CD31 staining. All
rabbits in the IRE treatment group experienced successful IRE without obvious
complications except for thoracic major muscle injury. A focused, complete and
well-defined ablation zone where tumor cells have been thoroughly eradicated was
detected by H&E staining, along with increasing TUNEL staining. The expression of
PCNA and CD31 was down-regulated at the periphery of the ablation region. As of
the last follow-up, 10 rabbits (67%) in IRE group demonstrated disease is under
control; 2 rabbits (13%) are in stable condition; 3 rabbits (20%) suffered from
disease progression; the remaining 5 rabbits were sacrificed for pathological
examination halfway through the study. Overall, the efficacy of IRE was
demonstrated by the creation of a complete ablation region, with increased
apoptosis in the ablation zone and decreased proliferation and microvessel
density of tumor tissue at the periphery. IRE is a promising local treatment for
breast cancer.
PMID- 28417252
TI - Effects of Parental Monitoring and Knowledge on Substance Use and HIV Risk
Behaviors Among Young Men Who have Sex with Men: Results from Three Studies.
AB - Young men who have sex with men (YMSM) are disproportionately impacted by
HIV/AIDS and have elevated rates of substance use. Parenting practices, such as
knowledge of child whereabouts and monitoring of behavioral rules, protect
against these outcomes among heterosexual youth. This article examined the
relationship between these parenting practices and substance use and HIV risk
behaviors among YMSM. Data are reported from three similar studies of YMSM:
ChiGuys (ages 14-18), Crew 450 (ages 16-22), and RADAR (ages 16-29). The ChiGuys
and RADAR studies report cross-sectional analyses, whereas Crew 450 reports
latent growth curve analyses. In ChiGuys and Crew 450, participants reported
significantly higher scores for parental knowledge of general activities than
parental knowledge of gay-specific activities. Parental knowledge of general
activities was significantly associated with less binge drinking in both samples
and with condomless sex in the ChiGuys sample. Parental monitoring was
significantly associated with less marijuana use and condomless sex in younger
RADAR participants (16-18 years) and with less drug use in older participants
(>18 years). Findings support the need for further research on the influences of
parents on YMSM health risk behaviors and the value of exploring family- and
parent-interventions to address YMSM health.
PMID- 28417253
TI - Body Image and Condomless Anal Sex Among Sexual Minority Men Living with HIV.
AB - The interaction of body dissatisfaction and appearance investment (importance and
effort ascribed to appearance) in relation to condomless anal sex has not
previously been examined. Body dissatisfaction in the context of varying degrees
of appearance investment may yield divergent sexual risk outcomes. Sexual
minority men living with HIV (N = 105) completed a battery of self-report
measures. A generalized linear model identified a significant interaction [b =
0.08 (95% CI 0.01, 0.16), p = 0.033] such that when appearance investment was
low, body dissatisfaction was associated with fewer condomless anal sex acts;
when appearance investment was high, body dissatisfaction was associated with
increased condomless anal sex.
PMID- 28417254
TI - Whom are we treating with adaptive servo-ventilation? A clinical post hoc
analysis.
AB - BACKGROUND: Recent evidence has shown that adaptive servo-ventilation (ASV) is
contraindicated in patients with predominant central sleep apnea (CSA) and
reduced left ventricular ejection fraction (LVEF <=45%). The objective of this
study was to assess the clinical usage of ASV in patients at the time-point of
the release of a safety warning by type of SDB, breathing pattern and LVEF.
METHODS: Patients of a cardiac and a respirology sleep center, both in Germany,
who received ASV therapy were contacted between May and October 2015.
Retrospective analyses included diagnostic polysomnography, polysomnography with
continuous positive airway pressure prior to ASV initiation and echocardiography.
Treatment emergent CSA was diagnosed after an appropriate treatment period on
CPAP. RESULTS: 285 patients receiving ASV therapy (91 in the cardiac and 194 in
the respirology setting) underwent diagnostic polysomnography. 233 (82%) patients
had severe SDB, 94 (33%) predominant CSA, and 185 (65%) periodic breathing. 20%
(n = 52) of patients had an LVEF of <=45%. The most common indications for ASV
were CSA in heart failure (41%) in the cardiac setting and treatment emergent CSA
(80%) diagnosed after an appropriate period on CPAP in the respirology setting.
The proportion of patients in whom ASV was contraindicated (CSA and LVEF <=45%)
was 16% in the cardiac setting and 9% in the respirology setting. CONCLUSION:
Clinical usage of ASV changed for a small subgroup of patients after release of
the SERVE-HF results. Nevertheless, ASV treatment should be monitored and
evaluated with diligence in the reminder indications.
PMID- 28417255
TI - Lower limb pain among workers: a cross-sectional analysis of the fifth European
Working Conditions Survey.
AB - OBJECTIVE: Develop a model to predict the prevalence of lower limb pain using
indicators of high workplace exposures based on the fifth European Working
Conditions Survey, evaluate its impact and explore its significance for work
related health problems. METHOD: Cross-sectional interview data of 35,372 workers
from 27 countries of the European Union in 2010 (EU27) were used to develop (20%
sample) and validate (80% sample) a logistic regression model for lower limb
pain. Independent variables included descriptions of working conditions,
assessments of physical and psychosocial exposures at work, and demographic
factors. The impact of the model was explored through the amount of lower limb
pain cases attributable to work and estimating work absences correlated with
lower limb pain. RESULTS: The resulting logistic model included ten risks
indicators and one preventive factor. The highest odds ratios (OR) corresponded
to "tiring or painful positions" OR 2.0, 99% confidence interval (99% CI) 1.9
2.2, and "not satisfied with level of working conditions in the job" (OR 1.6, 99%
CI 1.5-1.7). The prevalence of work-related lower limb pain was 16.5% for men and
15.8% for women for the 27 countries of the European Union. Estimates based on
the developed model revealed more than 34 million cases of work-related lower
limb pain, where four physical risks explained about 22 million cases. In
addition, more than 3 million days of absence from work in 2010 could be
attributed to lower limb pain. CONCLUSION: Lower limb pain is highly prevalent
among the European workforce and work exposures are a major contributing factor.
Effective workplace interventions should aim at improving working conditions at
workplaces with multiple risks.
PMID- 28417256
TI - To which extent social withdrawal at the age of 1 year is associated with IQ at 5
6 years old? Results of the EDEN mother-child cohort.
AB - The present study aims to determine to which extent social withdrawal at 1 year
is associated with the child's IQ at the end of the preschool period. Children (N
= 1045) from the EDEN mother-child cohort were assessed for social withdrawal
behaviours at 1 year by trained midwives using the Alarm Distress BaBy (ADBB)
scale. Midwives also examined infants' language and motor development at 1 year.
At the age 5-6 years, IQ scores were based on the WPPSI-III. Linear regression
models were used to determine the association between IQ and ADBB, adjusted for a
broad range of pre- and postnatal environmental factors and for language and
motor skills scores at 1 year. After adjusting for environmental factors,
children with social withdrawal at 1 years (ADBB >=5; N = 195) had significantly
lower IQ scores at 5-6 years (-2.81 IQ points; p value 0.007) compared to
children without social withdrawal (ADBB <5; N = 847). When motor and language
skills at 1 year were included in the previous model, no association between
social withdrawal and IQ at 5-6 years was found. Being socially withdrawn at 1
year is associated with lower IQ scores at 5-6 years. The potential influence of
these developmental aspects on each other (withdrawal behaviour and
language/motor skills) may occur early in development. Our results improve our
understanding of the outcomes of early social withdrawal behaviour and call for
early detection of delay in acquisition of language/motor skills among socially
withdrawn young children.
PMID- 28417257
TI - Additive effect of congenital heart disease and early developmental disorders on
attention-deficit/hyperactivity disorder and autism spectrum disorder: a
nationwide population-based longitudinal study.
AB - In this retrospective nationwide population-based case-control study, we
investigated the impact of congenital heart disease (CHD) on the development of
attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder
(ASD), which remains unclear. Children aged <18 years that were diagnosed with
CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from
the National Health Insurance Research Database in Taiwan. Non-CHD controls (n =
14,208) matched for age and sex (1:4) were selected from the same dataset. All
subjects were observed until December 31, 2011 or their death. Comorbid perinatal
conditions and early developmental disorders (EDD) that were diagnosed before
ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal
comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the
control group. Multivariate Cox regression analysis revealed that the CHD group
had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95%
confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after
adjusting for confounding comorbidities. EDD, but not perinatal comorbidities
were also independent risk factors for ADHD and ASD after adjustment. Subgroup
analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD
(HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD
than in non-CHD subjects without EDD. These findings suggested that CHD at birth
and EDD during early childhood were two independent risk factors for ADHD and ASD
and that concurrent CHD and EDD might additively increase these risks.
PMID- 28417258
TI - In vivo facial soft tissue depths of a modern adult population from Germany.
AB - Forensic facial reconstruction may be the final option available to draw public
attention in cases where the identity of an individual cannot be established by
standard identification methods. Two fundamental components of all forensic
facial reconstruction techniques are cranial morphology and soft tissue depth
databases. The purpose of this study was to extend such databases by providing a
complete set of accurate facial soft tissue thickness measurements, acquired from
a contemporary adult population from Germany. The material for the study
consisted of 320 (160 male, 160 female) anonymised multi-slice computerised
tomography (MSCT) scans of individuals drawn from a German population. In
Amira(r), 3D models of the surfaces of the skull and the facial skin were semi
automatically segmented using calculated thresholds and surface extraction
algorithms. Facial soft tissue depth was measured at 10 midline and 28 bilateral
anatomical landmarks. The analysis of facial soft tissue thickness versus BMI,
sex and age indicated that, at a number of the landmarks, facial soft tissue
depth is significantly (p < 0.05) influenced by all three biometric variables.
Facial soft tissue thickness increased with increasing BMI. The differences
between males and females were statistically significant (p < 0.05) for almost
all anatomical landmarks with the exception of a few in the region of the nasal
root and orbitals. Asymmetry was noted at over half of the bilateral landmarks.
The differences between the results from this sample and those obtained from
comparable databases contradict the hypothesis that population specificity
significantly influences facial soft tissue thickness.
PMID- 28417259
TI - Comparison between magnetic bead and qPCR library normalisation methods for
forensic MPS genotyping.
AB - Massively parallel sequencing (MPS) is fast approaching operational use in
forensic science, with the capability to analyse hundreds of DNA identity and DNA
intelligence markers in multiple samples simultaneously. The ForenSeqTM DNA
Signature Kit on MiSeq FGxTM (Illumina) workflow can provide profiles for
autosomal short tandem repeats (STRs), X chromosome and Y chromosome STRs,
identity single nucleotide polymorphisms (SNPs), biogeographical ancestry SNPs
and phenotype (eye and hair colour) SNPs from a sample. The library preparation
procedure involves a series of steps including target amplification, library
purification and library normalisation. This study highlights the comparison
between the manufacturer recommended magnetic bead normalisation and quantitative
polymerase chain reaction (qPCR) methods. Furthermore, two qPCR chemistries,
KAPA(r) (KAPA Biosystems) and NEBNext(r) (New England Bio Inc.), have also been
compared. The qPCR outperformed the bead normalisation method, while the
NEBNext(r) kit obtained higher genotype concordance than KAPA(r). The study also
established an MPS workflow that can be utilised in any operational forensic
laboratory.
PMID- 28417260
TI - Five-year survival analysis of surgically resected gastric cancer cases in Japan:
a retrospective analysis of more than 100,000 patients from the nationwide
registry of the Japanese Gastric Cancer Association (2001-2007).
AB - BACKGROUND: The aim of this retrospective study was to investigate the tumor
characteristics, surgical details, and survival distribution of surgically
resected cases of gastric cancer from the nationwide registry of the Japanese
Gastric Cancer Association. METHODS: Data from 118,367 patients with primary
gastric carcinoma who underwent resection between 2001 and 2007 were included in
the survival analyses. The 5-year survival rates were calculated for various
subsets of prognostic factors. RESULTS: The median age of the patients was 67
years. The proportions of patients with pathological stage (Japanese Gastric
Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%,
11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of
operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who
were treated by resection was 71.1%. The 5-year overall survival rates of
patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were
91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease
specific survival rates in the patients with pT1 (mucosa) disease after D1+
dissection of lymph node station no. 7 (D1 + alpha), D1+ dissection of lymph node
station nos. 7, 8, and 9 (D1+ beta), and D2 lymphadenectomy were 99.4%, 99.6%,
and 99.1% respectively. The 5-year disease-specific survival rates in the
patients with pT1 (submucosa) disease after D1 + alpha, D1 + beta, and D2
lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. CONCLUSION: Detailed
analyses of the data from more than 100,000 patients show the recent trends of
the outcomes of gastric cancer treatment in Japan and provide baseline
information for use by medical communities around world.
PMID- 28417261
TI - Neutrophil Infiltration and Matrix Metalloproteinase-9 in Lacunar Infarction.
AB - We use the modified pial vessel disruption rat model to elucidate the cellular
and molecular mechanisms of cavitation as it plays a role in lacunar infarction.
Here we discuss the similarities between the genesis of pulmonary cavitation in
various animal models and lacunar infarction in the cerebral cortex of rats. Both
pathological processes involve the creation of a cavity surrounded by fibroblasts
or reactive astrocytes. A crucial step in both, the lung and the cerebral cortex,
appears to be the migration of neutrophils across the endothelial barrier into
the parenchyma. In the lung and cerebral cortex this involves release of matrix
metalloproteinase-9 (MMP-9). Inside the parenchyma neutrophils continue to
release MMP-9. In both situations batimastat (BB-94) and minocycline reduce
release of MMP-9 and prevent cavitation. In the cerebral cortex MMP-9 release by
resident microglia plays an additional role. We therefore advance the hypothesis
that cavitation in both tissues is driven by MMP-9 originating from invading
neutrophils. Therapeutic intervention has to focus on these blood-borne intruder
cells and specific MMP actions. Batimastat and its derivatives (marimastat, BB
1101, mCGS-27023-A, ilomastat, GM6001, CTK8G1150) are already in clinical or
experimental use in humans for anti-cancer treatment, and these clinically
relevant drugs could be repurposed to act as anti-inflammatory to counter
neutrophil contribution to lung or cerebral cortex cavitation.
PMID- 28417262
TI - Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via
Activation of the Wnt/beta-Catenin Signaling Pathway After Spinal Cord Injury.
AB - The spinal cord is highly sensitive to spinal cord injury (SCI) by external
mechanical damage, resulting in irreversible neurological damage. Activation of
the Wnt/beta-catenin signaling pathway can effectively reduce apoptosis and
protect against SCI. Melatonin, an indoleamine originally isolated from bovine
pineal tissue, exerts neuroprotective effects after SCI through activation of the
Wnt/beta-catenin signaling pathway. In this study, we demonstrated that melatonin
exhibited neuroprotective effects on neuronal apoptosis and supported functional
recovery in a rat SCI model by activating the Wnt/beta-catenin signaling pathway.
We found that melatonin administration after SCI significantly upregulated the
expression of low-density lipoprotein receptor related protein 6 phosphorylation
(p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and beta-catenin protein in the
spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord
ventral horn and improved the locomotor functions of rats after SCI. Melatonin
administration after SCI also reduced the expression levels of Bax and cleaved
caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl
transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive
cells, but increased the expression level of Bcl-2. These results suggest that
melatonin attenuated SCI by activating the Wnt/beta-catenin signaling pathway.
PMID- 28417263
TI - Rosuvastatin Attenuates High-Salt and Cholesterol Diet Induced Neuroinflammation
and Cognitive Impairment via Preventing Nuclear Factor KappaB Pathway.
AB - Recent attention is focused on the impact of diet on health and mental well
being. High-salt and cholesterol diet (HSCD) is known to be associated with
neuroinflammation which is the predominant factor for neurodegenerative disease
like Alzheimer disease (AD). In the present study, we examined the
neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against
HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated
that HSCD-induced cognitive impairment as determined by Morris water maze (MWM)
task. HSCD also activated nuclear factor kappaB (NF-kB) signaling pathway. The
cytokine response was measured using a cytometric bead-based assay quantified by
flow cytometry. Treatment with rosuvastatin decreased the production of nitric
oxide (NO), tumor necrosis factor alpha (TNF-alpha) and increased interleukin-10
(IL-10) in a dose-dependent manner. Our results also demonstrated that the
rosuvastatin modulates neuronal cell death by inhibiting the overexpression of NF
kB in the CA1 region of hippocampus. In addition, molecular docking study of
rosuvastatin indicated high affinity and tighter binding capacity for the active
site of the NF-kB. These results suggest that HSCD-triggered inflammatory
response and cognitive impairment may be associated with NF-kappaB signaling
pathway. Therefore, treatment with rosuvastatin could be a potential new
therapeutic strategy for sporadic dementia of AD.
PMID- 28417264
TI - Branched-Chain Amino Acids and Brain Metabolism.
AB - This review aims to provide a historical reference of branched-chain amino acid
(BCAA) metabolism and provide a link between peripheral and central nervous
system (CNS) metabolism of BCAAs. Leucine, isoleucine, and valine (Leu, Ile, and
Val) are unlike most other essential amino acids (AA), being transaminated
initially in extrahepatic tissues, and requiring interorgan or intertissue
shuttling for complete catabolism. Within the periphery, BCAAs are essential AAs
and are required for protein synthesis, and are key nitrogen donors in the form
of Glu, Gln, and Ala. Leucine is an activator of the mammalian (or mechanistic)
target of rapamycin, the master regulator of cell growth and proliferation. The
tissue distribution and activity of the catabolic enzymes in the peripheral
tissues as well as neurological effects in Maple Syrup Urine Disease (MSUD) show
the BCAAs have a role in the CNS. Interestingly, there are significant
differences between murine and human CNS enzyme distribution and activities. In
the CNS, BCAAs have roles in neurotransmitter synthesis, protein synthesis, food
intake regulation, and are implicated in diseases. MSUD is the most prolific
disease associated with BCAA metabolism, affecting the branched-chain alpha-keto
acid dehydrogenase complex (BCKDC). Mutations in the branched-chain
aminotransferases (BCATs) and the kinase for BCKDC also result in neurological
dysfunction. However, there are many questions of BCAA metabolism in the CNS (as
well as the periphery) that remain elusive. We discuss areas of BCAA and BCKA
metabolism that have yet to be researched adequately.
PMID- 28417265
TI - Advancing Drug Discovery and Development Using Molecular Imaging (ADDMI): an
Interest Group of the World Molecular Imaging Society and an Inaugural Session on
Positron Emission Tomography (PET).
AB - Multi-modality molecular imaging techniques have expanded the role of imaging
biomarkers in the pharmaceutical industry and are beginning to streamline the
drug discovery and development process. The World Molecular Imaging Society
(WMIS) serves as a forum for discussing innovative and exploratory multi-modal,
interdisciplinary molecular imaging research with a mission of bridging the gap
between pathology and in vivo imaging. To formalize the role of the WMIS in
pharmaceutical research efforts, members of the society have formed an interest
group entitled Advancing Drug Discovery and Development using Molecular Imaging
(ADDMI). The ADDMI interest group launched their efforts at the 2016 World
Molecular Imaging Congress by hosting a session of invited lectures on
translational positron emission tomography (PET) imaging in the central nervous
system. This article provides a synopsis of those lectures and frames the role of
translational imaging biomarker strategies in the drug discovery and development
process.
PMID- 28417266
TI - Guided longer pulses from a diagnostic ultrasound and intraclot microbubble
enhanced catheter-directed thrombolysis in vivo.
AB - The mechanism of ultrasound thrombolysis (UT) is generally attributed to
cavitation. The insufficiency of microbubbles (MB) to serve as cavitation nuclei
in the vessel-obstructing thrombi significantly reduces the effectiveness of UT.
Taking advantage of the widely performed catheter-directed therapy (CDT), in a
thrombo-embolized rabbit IVC model with a simultaneous catheter directed rt-PA
thrombolysis procedure, guided moderate mechanical index longer pulses from a
modified diagnostic ultrasound transducer, combined with an intraclot infusion of
MB, significantly accelerated the thrombolysis process. The higher thrombolysis
efficacy score and consistent elevated post-treatment plasma concentration level
of D-Dimer, a product of fibrinolysis, both indicated the superiority of CDT + UT
over CDT/UT alone. Pathologic examination of the treated occluded IVC segments
revealed an almost complete dissolution of the thrombi treated with CDT + UT.
There was no evidences of thrombo-embolism or local thrombus formation in the
cardiac-pulmonary vessels. Combined with intraclot infusion of MB, guided longer
pulse ultrasound from a diagnostic transducer is able to safely and significantly
improve a catheter-directed thrombolysis procedure. It thus has the potential to
achieve earlier clot removal, administration of a lower dosage of thrombolytic
agent and, consequently, a lower incidence of thrombolysis-related side effects.
PMID- 28417267
TI - Preemptive warfarin dose reduction after initiation of sulfamethoxazole
trimethoprim or metronidazole.
AB - To evaluate the utility of a preemptive warfarin dose reduction at the time of
initiation of either sulfamethoxazole-trimethoprim or metronidazole, a
retrospective chart review of patients who received an outpatient prescription
for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from
July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans
who had a warfarin dose reduction and those who did not within 120 h (5 days) of
antibiotic initiation. The primary outcome compared the pre-and post-antibiotic
International Normalized Ratio (INR) of patients in the intervention group
(warfarin dose reduction) with those in the control group (no intervention).
Secondary outcomes assessed incidence of thromboembolic and major bleeding events
within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine
patients had at least one follow-up appointment; 126 follow-up visits were
evaluated. There was a statistically significant difference for the change in
therapeutic INR at the first follow-up appointment (p = 0.029) for those patients
in the control group. On average, the patients in the intervention group required
fewer follow-up visits (p = 0.019). There were no statistically significant
differences for the overall rate of therapeutic INR values between groups, as
well as no instances of a thromboembolic or major bleeding events during the
follow-up period. Clinically significant differences were observed for patients
who received a preemptive warfarin dose reduction upon initiation of
sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention
group required fewer follow-up appointments and were more likely maintain a
therapeutic INR within the 30 days following the antibiotic course. Results of
this study will be presented the at Pharmacy and Therapeutics committee in an
effort to seek approval for policy development to initiate a local preemptive
warfarin dose adjustment as a standard of practice.
PMID- 28417268
TI - Sexual Behavior Among Persons With Cognitive Impairments.
AB - Although the cognitively impaired are frequently included in heterogeneous
studies of problematic sexual behavior, the epidemiology, etiology, and approach
to assessment and treatment of persons with dementia and intellectual disability
are distinct from those of the general population. The incidence of inappropriate
sexual behavior among the intellectually disabled is 15-33%; however, the nature
tends to be more socially inappropriate than with violative intent. Limited
sociosexual education is a large contributor, and better addressing this area
offers a target for prevention and treatment. A thorough clinical assessment of
problematic sexual behaviors in the cognitively impaired requires understanding
the patient's internal experience, which can be challenging. Assessment tools
validated for the general population have not been validated for this population.
Very few studies have assessed treatment approaches specifically among the
cognitively impaired; however, research does suggest utility in habilitative,
psychotherapeutic, and pharmacologic approaches which have been validated among
the general population.
PMID- 28417269
TI - Anxiety Disorders and Temperament-an Update Review.
AB - PURPOSE OF REVIEW: The review focused on associations between temperament
dimensions and clinical features in different anxiety disorders, likewise in
obsessive-compulsive disorder in clinical samples of adults. A literature search
was conducted in the Medline and PsycINFO databases covering the years 2010-2016.
A systematic review and grading of the level of evidence for an association
between temperament dimension scores and clinical features in each disorder were
performed. RECENT FINDINGS: Twenty papers reporting 18 different studies were
included. Five of the papers focused on panic disorder (PD), five on social
anxiety disorder (SAD), three on post-traumatic stress disorder (PTSD), one on
generalized anxiety disorder (GAD), three on obsessive-compulsive disorder (OCD),
and an additional three papers on several anxiety disorders. The review
consolidates the finding that trait anxiety, especially as assessed by
Cloninger's model or the five-factor model, is a phenomenon common to all anxiety
disorders and OCD. More follow-up studies including large samples are needed to
differentiate the dimensional profiles of trait anxiety in specific disorders.
PMID- 28417270
TI - Current Reports on Perinatal Intimate Partner Violence.
AB - PURPOSE OF REVIEW: The purpose of this study was to review the literature on
perinatal intimate partner violence, focusing on recent knowledge to guide mental
health professionals on the best approaches to identify and treat women exposed
to perinatal intimate partner violence. RECENT FINDINGS: Risk factors have been
broadened from individual victim and perpetrator factors to include relationship,
community, and societal factors which interact together. Better information is
now available on how to identify, document, and treat women exposed to violence
around the time of conception, pregnancy, and the postpartum period. Recent
information helps psychiatrists and other mental health professionals assist
women exposed to violence related to the perinatal period; however, further
research is needed to provide improved evidence for optimal interventions for
better patient outcomes.
PMID- 28417271
TI - Antimicrobial effects of Manuka honey on in vitro biofilm formation by
Clostridium difficile.
AB - Clostridium difficile is the cause of the nosocomial C. difficile infection
(CDI). The conventional antibiotics used in CDI therapy are often unsuccessful,
and recurrent infections may occur. Biofilm formation by C. difficile is
associated with chronic or recurrent infections; biofilms may contribute to
virulence and impaired antimicrobial efficacy. Manuka honey, derived from the
Manuka tree (Leptospermum scoparium), is known to exhibit antimicrobial
properties that are associated with its significant content of methylglyoxal, a
natural antibiotic. The aim of the present study was to determine the
antimicrobial effect of Manuka honey on clinical C. difficile strains belonging
to four prominent polymerase chain reaction (PCR) ribotypes (RTs) (RT017, RT023,
RT027 and RT046) and on their biofilm formation in vitro. Minimal inhibitory and
bactericidal concentrations (MICs and MBCs, respectively) were determined using
the broth dilution method. The biomass of the biofilm and the clearance of C.
difficile biofilms by Manuka honey were determined using the crystal violet
staining method. The MIC and MBC of Manuka honey for C. difficile strains were
equal at 6.25% (v/v). PCR RT027 strains produced more biofilm in vitro than the
other examined strains. Manuka honey effectively inhibited biofilm formation by
C. difficile strains of different PCR RTs.
PMID- 28417272
TI - Early administration of neuraminidase inhibitors in adult patients hospitalized
for influenza does not benefit survival: a retrospective cohort study.
AB - The administration of neuraminidase inhibitors (NAIs) within 2 days after the
onset of symptoms (early NAI therapy) has been shown to reduce mortality in adult
patients with severe influenza. However, there is no sufficiently solid evidence
supporting the effectiveness of early NAI therapy on mortality. We reviewed the
clinical data from 506 adult patients who were hospitalized for influenza between
March 2010 and March 2014, to investigate the impact of early NAI therapy on
mortality. Nearly one-third of the study patients were infected with influenza B
(influenza A, influenza B, and co-infection of both in 68.8%, 28.1%, and 3.2%,
respectively), and were diagnosed using the polymerase chain reaction (PCR)
method (33.6%). Less than half (233, 46.0%) had received early NAI therapy.
Patients with early NAI therapy were admitted to the hospital earlier, more
frequently infected with influenza A, and more frequently diagnosed using rapid
influenza detection tests compared to those without early NAI therapy. Although
patients without early NAI therapy presented with more serious clinical
manifestations, such as an initial symptom of dyspnea, pneumonia, and intensive
care unit admission, than those with early NAI therapy, the in-hospital mortality
of the former (2.9%, 8/273) did not differ from that of the latter (3.4%, 8/233)
(p = 0.75). We did not find a reduction in mortality associated with early NAI
therapy in adult patients hospitalized for influenza. Further clinical studies
including a large number of influenza B-infected patients with virus
identification using PCR methodology rather than viral culture may be required to
confirm the beneficial impact of early NAI therapy on mortality.
PMID- 28417273
TI - Maternal height and breast cancer risk: results from a study nested within the
EPIC-Greece cohort.
AB - The positive association of adult height with breast cancer (BC) risk has been
hypothesized to be partly accounted for by an association of this risk with
maternal height (operating in utero to modify hormone effects). In a case-control
study (271 BC patients and 791 controls) nested within the EPIC-Greece cohort, we
applied mediation analysis to calculate the direct and indirect (through the
woman's own height) effect of maternal height on BC risk. Per 5 cm increase in
maternal height and depending on its reference value: the indirect effect odds
ratio ranges from 1.02 to 1.07; the direct effect odds ratio from 1.06 to 1.11;
and the total (direct and indirect effects) from 1.08 to 1.19. The effect sizes
consistently increased for higher reference categories of maternal height, but
did not generally reach statistical significance, possibly due to the limited
sample size.
PMID- 28417274
TI - Dr. Rafael F. Capella, MD.
PMID- 28417275
TI - RNA silencing in the life cycle of soybean: multiple restriction systems and
spatiotemporal variation associated with plant architecture.
AB - The expression of transgenes introduced into a plant genome is sometimes
suppressed by RNA silencing. Although local and systemic spread of RNA silencing
have been studied, little is known about the mechanisms underlying spatial and
temporal variation in transgene silencing between individual plants or between
plants of different generations, which occurs seemingly stochastically. Here, we
analyzed the occurrence, spread, and transmission of RNA silencing of the green
fluorescent protein (GFP) gene over multiple generations of the progeny of a
single soybean transformant. Observation of GFP fluorescence in entire plants of
the T3-T5 generations indicated that the initiation and subsequent spread of GFP
silencing varied between individuals, although this GFP silencing most frequently
began in the primary leaves. In addition, GFP silencing could spread into the
outer layer of seed coat tissues but was hardly detectable in the embryos. These
results are consistent with the notion that transgene silencing involves its
reset during reproductive phase, initiation after germination, and systemic
spread in each generation. GFP silencing was absent in the pulvinus, suggesting
that its cortical cells inhibit cell-to-cell spread or induction of RNA
silencing. The extent of GFP silencing could differ between the stem and a
petiole or between petiolules, which have limited vascular bundles connecting
them and thus deter long-distant movement of silencing. Taken together, these
observations indicate that the initiation and/or spread of RNA silencing depend
on specific features of the architecture of the plant in addition to the
mechanisms that can be conserved in higher plants.
PMID- 28417276
TI - Assessing ASD in Adolescent Females with Anorexia Nervosa using Clinical and
Developmental Measures: a Preliminary Investigation.
AB - The aim of this study was to use standardised, clinical assessment tools to
explore the presence of Autism Spectrum Disorder (ASD) symptoms in a sample of
adolescent females with Anorexia Nervosa (AN), receiving either day-patient or
inpatient treatment for their eating disorder and to determine whether any such
symptoms were present during the early developmental period, a requirement for a
diagnosis of ASD. Using a cross-sectional design, 40 females aged between 12 and
18 were recruited from inpatient and day-patient eating disorder services. All
participants had a diagnosis of AN and were assessed for symptoms of ASD using
the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2). If participants
scored at or above clinical cut-off on the ADOS-2, their parents were asked to
complete the Developmental, Dimensional and Diagnostic Interview, short version
(3Di-sv). Of the 40 participants assessed, 21 scored above cut-off on the ADOS-2.
When developmental history was obtained, only four participants scored above cut
off on all sub-scales of the 3Di-sv, thus meeting full research criteria for ASD.
This study suggests that 10% of adolescents with AN from inpatient or day-patient
settings may have diagnosable ASD, while a further 40% may show symptoms of ASD,
which may arise from the ill-state of AN or are not supported by parental report.
PMID- 28417277
TI - Clandestine charisma of the charm needles: a radiologist's challenge.
AB - A 94-year-old Korean woman was seen in the Emergency Department after a fall. CT
examination of the maxillofacial region found multiple small linear metallic
densities in the subcutaneous soft tissues of the face. The appearance of these
densities was unchanged when compared to a study performed 2 years prior;
however, the imaging interpretations of these densities were markedly different.
Additional imaging during the course of her hospital stay demonstrated numerous
similar densities in the breasts, abdomen, hips, and legs-finally diagnosed as
"charm needles." Although common practice in Southeast Asia, with ever increasing
globalization, these needles, or "susuks," are being seen with greater frequency
in North America. Here, we review the imaging appearance of a bizarre case of
these charm needles so as to raise awareness of this potential diagnostic
challenge and help the radiologist avoid confusion when interpreting images.
PMID- 28417278
TI - Comment to: "No enterocutaneous fistula development in a cohort of 695 patients
after incisional hernia repair using intraperitoneal uncoated polypropylene mesh"
by Brandi, C.D., Roche, S., Bertone, S. et al. Hernia (2017) 21: 101.
PMID- 28417280
TI - New isolation technique for enteroatmospheric fistula in Bjorck 4 open abdomen.
PMID- 28417279
TI - Tackers versus glue mesh fixation: an objective assessment of postoperative acute
and chronic pain using inflammatory markers.
AB - PURPOSE: Laparoscopic hernioplasty has become a popular choice for inguinal
hernia repair since its advent in 1990s. Postoperative pain is an undesirable
clinical outcome impairing daily activity of 22.5% of patients. The aim of this
study is to evaluate postoperative acute and chronic pain via inflammatory
markers as an objective assessment following tacks or glue mesh fixation in TEP
repair. METHODS: Sixty-six (66) patients with unilateral uncomplicated inguinal
hernia were randomized into 34 patients in the tacker and 32 patients in
cyanoacrylate glue mesh fixation in TEP repair. The extent of surgical trauma was
evaluated by measuring inflammatory markers of C-reactive protein, white blood
cell count at 48 h, and ESR at 3 months postoperatively. Postoperative acute and
chronic pain was assessed by recording the visual analogue scale scores and
surgical complications were recorded over 3 months of the study period. RESULTS:
The median CRP and WBC levels at postoperative 48 h in both groups raised
significantly from the baseline values (p < 0.05), however, did not differ
significantly between the two study groups at 48 h (p > 0.05). The median ESR
level increased significantly at 3 months postoperatively from baseline in the
glue mesh fixation group only (p < 0.05), however, did not differ significantly
between the two study groups (p > 0.05). There was no significant difference for
VAS scores at all timelines between the tacker and glue mesh fixation group (p >
0.05). CONCLUSION: Cyanoacrylate glue mesh fixation technique as an alternative
method to mechanical fixation in TEP repair is comparable to tacker and can be
considered to be safe and feasible.
PMID- 28417281
TI - Historical record of anthropogenic polycyclic aromatic hydrocarbons in a lake
sediment from the southern Tibetan Plateau.
AB - High-altitude lake sediments can be used as natural archives to reconstruct the
history of pollutants. In this work, the temporal distribution of polycyclic
aromatic hydrocarbons (PAHs) was determined in a sediment core collected from the
southern Tibetan Plateau (TP), which was dated by using the 210Pb dating method
and validated with the 137Cs fallout peak. The concentrations of the
anthropogenic PAHs (Sigma8PAH) in the sediment core ranged from 0.83 to 12 ng/g
dw, and the fluxes of the Sigma8PAH were in the range of 2.1-27 g/cm2/year. The
temporal variations in the concentration and input flux of anthropogenic PAHs
were low with little variability before the 1950s, and then gradually increased
from the 1950s to the 1980s, and an accelerated increase was observed after the
early 1980s. The content of total organic carbon played an insignificant role in
affecting the time trends of PAHs in the sediment core. Diagnostic concentration
fractions of PAH components indicate PAHs in the lake sediment of the southern TP
which are mainly from biomass burning and/or from long-range atmospheric
transport.
PMID- 28417282
TI - Coastal modification of a scene employing multispectral images and vector
operators.
AB - Changes in sea level, wind patterns, sea current patterns, and tide patterns have
produced morphologic transformations in the coastline area of Tamaulipas Sate in
North East Mexico. Such changes generated a modification of the coastline and
variations of the texture-relief and texture of the continental area of
Tamaulipas. Two high-resolution multispectral satellite Satellites Pour
l'Observation de la Terre images were employed to quantify the morphologic change
of such continental area. The images cover a time span close to 10 years. A
variant of the principal component analysis was used to delineate the
modification of the land-water line. To quantify changes in texture-relief and
texture, principal component analysis was applied to the multispectral images.
The first principal components of each image were modeled as a discrete
bidimensional vector field. The divergence and Laplacian vector operators were
applied to the discrete vector field. The divergence provided the change of
texture, while the Laplacian produced the change of texture-relief in the area of
study.
PMID- 28417283
TI - Bis-anthracycline WP760 abrogates melanoma cell growth by transcription
inhibition, p53 activation and IGF1R downregulation.
AB - Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active
against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to
DNA intercalation, interference with topoisomerase activity, and induction of
double-stranded DNA breaks. Since modification of anthracyclines can profoundly
affect their pharmacological properties we attempted to elucidate the mechanism
of action, and identify possible molecular targets, of bis-anthracycline WP760
which previously demonstrated anti-melanoma activity at low nanomolar
concentrations. We studied the effect of WP760 on several human melanoma cell
lines derived from tumors in various development stages and having different
genetic backgrounds. WP760 inhibited cell proliferation (IC50 = 1-99 nM),
impaired clonogenic cell survival (100 nM), and inhibited spheroid growth (>=300
nM). WP760 did not induce double-stranded DNA breaks but strongly inhibited
global transcription. Moreover, WP760 caused nucleolar stress and led to
activation of the p53 pathway. PCR array analysis showed that WP760 suppressed
transcription of ten genes (ABCC1, MTOR, IGF1R, EGFR, GRB2, PRKCA, PRKCE, HDAC4,
TXNRD1, AKT1) associated with, inter alia, cytoprotective mechanisms initiated in
cancer cells during chemotherapy. Furthermore, WP760 downregulated IGF1R and
upregulated PLK2 expression in most of the tested melanoma cell lines. These
results suggest that WP760 exerts anti-melanoma activity by targeting global
transcription and activation of the p53 pathway and could become suitable as an
effective therapeutic agent.
PMID- 28417284
TI - A phase I dose-escalation study of the safety and pharmacokinetics of a tablet
formulation of voxtalisib, a phosphoinositide 3-kinase inhibitor, in patients
with solid tumors.
AB - Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in
capsule formulation in patients with solid tumors. This Phase I study assessed
safety and pharmacokinetics of voxtalisib administered as immediate-release
tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose
escalation design was used. Adverse events (AEs), pharmacokinetics (PK), food
effect and tumor response were evaluated. Results Thirty-two patients received
voxtalisib doses ranging from 50 mg to 70 mg once daily (QD) and 17 patients
received voxtalisib doses ranging from 30 mg to 50 mg twice daily (BID), for two
28-day cycles. Dose-limiting toxicities (DLTs) were Grade 3 fatigue (two patients
at 70 mg QD, one patient at 40 mg BID) and Grade 3 rash (two patients at 50 mg
BID). The maximum tolerated dose (MTD) was 60 mg for QD and 40 mg for BID
regimens. Common treatment-emergent AEs were diarrhea (41%), nausea (37%) and
fatigue (33%). Voxtalisib appeared to follow linear PK, with a general increase
in plasma exposure with dose and no significant accumulation. Administration with
food caused a slight decrease in exposure; however, given the high variability
observed in the exposure parameters, this should be interpreted with caution.
Best response was stable disease in 29% and 50% of patients (QD and BID regimens,
respectively). Conclusions The safety profile of voxtalisib tablets at the MTD in
patients with solid tumors was consistent with that observed with voxtalisib
capsules. Given the limited activity observed across multiple clinical trials, no
further trials of voxtalisib are planned.
PMID- 28417285
TI - Alcohol and thiamine deficiency trigger differential mitochondrial transition
pore opening mediating cellular death.
AB - Accumulating evidence has shown that binge-type alcohol intake in mothers
interferes with thiamine deficiency (TD) to promote the fetal alcohol syndrome
(FAS). Developmental alcohol or TD exposures act either synergistically or
separately to reproduce FAS features e.g. intrauterine growth retardation and
related microcephaly characterized by extensive cellular death induced by one
another neurotoxicant. However molecular and cellular mechanisms underlying
apoptosis in both alcohol and TD toxicities are unknown. The current review
addresses mechanisms of apoptosis underlying alcohol and TD toxicities for
further understanding FAS pathology. This study indicates two different
mitochondria pathways regulating cellular death: The first mechanism may engage
alcohol which activates the c-subunit ring of the F0-ATP synthase to form MPT
pore-dependent apoptosis; following the second mechanism, TD activates CyP-D
translocation from mitochondrial matrix towards the mitochondrial inner membrane
to form MPT pore-dependent necrosis. These studies shed light upon molecular and
cellular mechanisms underlying apoptosis and necrosis in developemental brain
disorders related to alcohol and thiamine deficiency, in hopes of developing new
therapeutic strategies for FAS medication.
PMID- 28417286
TI - Retraction Note to: Advanced oxidation protein products induce chondrocyte death
through a redox-dependent, poly(ADP-ribose) polymerase-1-mediated pathway.
PMID- 28417287
TI - Predictors of arrhythmia recurrence after balloon cryoablation of atrial
fibrillation: the value of CAAP-AF risk scoring system.
AB - PURPOSE: In the present study, we aimed to test the value of CAAP-AF score for
prediction of atrial fibrillation (AF) recurrence at follow-up in a group of our
patients treated by balloon cryoablation. METHODS: A total of 283 symptomatic
drug-refractory AF patients [261 (92%) with paroxysmal AF] who underwent
pulmonary vein isolation (PVI) with second-generation cryoballoon between April
2012 and October 2016 were included. The CAAP-AF score was calculated for every
patient. RESULTS: A total of 283 patients [68 female (20%), mean age 59.8 +/-
11.4 years] were included in the present analysis. Eighty-nine patients (31%) had
hypertension and 13 (4%) had coronary artery disease. The mean left atrial
diameter and left ventricular ejection fraction were 40.6 +/- 7.0 mm and 60.0 +/-
9.1%, respectively. The mean CHA2DS2-VASc score was 1.2 +/- 1.1, and mean number
of prior failed antiarrhythmic drugs was 1.4 +/- 0.8. At 18 +/- 6 months follow
up, 25 patients (8.87%) developed AF recurrence. The recurrence rate was as
follows: 3.17% (score 0-3), 8.47% (score 4), 16.28% (score 5), 6.67% (score 6),
23.08% (score 7), and 36.36% (score >=8). The recurrence rate was 4.86% at a
score <5 and 16.49% at a value >=5; a score cutoff >=5 predicted AF recurrence
with a sensitivity 64% and specificity 68%. CONCLUSIONS: The present analysis
suggests the usefulness of CAAP-AF scoring system, with its simple and easily
obtained six clinical variables, to predict AF recurrence after PVI by means of
second-generation cryoballoon. A score value >=5 predicted AF recurrence with a
sensitivity 64% and specificity 68%.
PMID- 28417288
TI - Troponin T elevation after permanent pacemaker implantation.
AB - PURPOSE: The objective of the study is to study the incidence, significance, and
factors associated with cardiac troponin T (CTNT) elevation after pacemaker
implantation. METHODS: Three hundred seventy-four patients (104 single-chamber
pacemakers or ICD, 243 dual-chamber pacemakers, and 27 cardiac resynchronization
therapy/cardiac resynchronization therapy defibrillator) who had normal levels of
CTNT at baseline and underwent implantation of a permanent pacemaker system were
included in this study. Serum levels of CTNT were measured at baseline, 6 and 24
h after the implantation procedure. RESULTS: The median of CTNT levels increased
from 0.012 ng/mL at baseline to 0.032 and 0.019 ng/mL at 6 and 24 h after the
procedure, respectively (all p < 0.0001). Elevated CTNT levels were noted in 208
patients (55.6%) at 6 h after the implantation, among which 29 patients (7.8%)
had CTNT levels exceeding the range of minimal myocardial damage (>0.09 ng/mL).
After 1-year follow-up, the incidence of complications including dislodgement of
the lead, pocket infection, pneumothorax, hemothorax, and vein thrombus and
cardiac outcomes including hospitalization of heart failure, coronary artery
disease, arrhythmia, and cardiovascular mortality was not significantly different
between the normal and elevated CTNT groups at 6 h after the procedure. By
logistic regression analysis, gender, N-terminal pro-B type natriuretic peptide
(NT-pro-BNP) at baseline, left ventricular ejection fractions (LVEF), estimated
glomerular filtration rate (eGFR), and fluoroscopy time were independently
associated with CTNT elevation after adjusted for age, pacemaker types, right
ventricle lead location (RVA or RVOT), heart function, and left ventricular end
systolic dimension. CONCLUSIONS: Pacemaker implantation was found to be
accompanied with CTNT elevation in 55.6% of the patients at 6 h after the
procedure, and its kinetics were fast, which might not be related to the
complications and adverse cardiac outcomes within 1 year of follow-up. Moreover,
gender, NT-pro-BNP at baseline, LVEF, eGFR, and fluoroscopy time were found to be
independent predictors of CTNT elevation.
PMID- 28417289
TI - Reporting the margin in pancreaticoduodenectomies: R0 versus R1.
AB - AIM: This study was conducted to analyze the changes in margin positivity in
pancreaticoduodenectomies, on using a standardized protocol, which bread loafs
the pancreas and duodenum in the axial plane for adenocarcinomas arising in the
pancreatic head, ampulla, terminal common bile duct (CBD), and duodenum, and then
to assess whether these tumor subsets involve the margins in different ways.
METHODS: The analysis was performed on 70 consecutive specimens, the pre-protocol
specimens serving as the control group. RESULTS AND CONCLUSIONS: Tumors
originating from the pancreatic head, ampulla, terminal CBD, and duodenum showed
a consistent increase in their R1 incidence, post-protocol. Ampullary tumors
showed the greatest upward change in R1 positivity. The highest incidence of
margin positivity was seen in pancreatic head adenocarcinomas (80%), then distal
CBD tumors (60%), and finally the ampullary tumors (39%). In pancreatic head
adenocarcinomas, R1 increased from 55% to 80%, distal CBD from 50% to 60%, and
ampullary from 17% to 39%. Duodenal adenocarcinomas had no R1 in both pre- and
post-protocol groups. The tumors also had different patterns of margin
involvement. Ampullary tumors involved only the posterior margin, pancreatic
adenocarcinomas involved the superior mesenteric vein (SMV) groove more often
than the posterior margin, and distal CBD tumors involved the posterior margin
and SMV groove equally. The size of the tumor made a significant difference in
pancreatic head carcinomas with tumor size less than or equal to 2 cm, showing an
R1 incidence of 38%, while those above 2 cm had an R1 incidence of 68%.
PMID- 28417290
TI - Unilateral external fixator in the treatment of humeral shaft fractures: results
of a single center retrospective study.
AB - BACKGROUND: The aim of our work is to evaluate and critically analyze long-term
clinical and radiological data of a new unilateral external fixator (MIKAI KIT
FEP(c)-Mikai S.p.A, Genoa, Italy), in the treatment of humeral shaft fractures.
MATERIALS AND METHODS: We reviewed 47 patients affected by humeral fractures that
underwent surgery from July 2010 to March 2016 with unilateral external fixator.
Demographic characteristics of the patients were recorded, which included age,
sex and baseline comorbidities and mechanism of injury. Surgical data such as
time of surgery and time of fixation according to AO-type of fracture, clinical
objective and subjective outcomes were collected. RESULTS: The mean follow-up was
50.4 months (range 12-74). The patients' average age was 41.8 years (range 14
92). Mean surgical time was 66.8 (+/-37.7 min); and mean time of fixation was 4.5
(+/-1.7 months). We observed five delayed union (10.6%); one refracture (2.1%);
and one case of non-union (2.1%) who underwent a revision surgery with nailing.
No malunion was detected. Average quick-DASH was 11.7 (+/-14.8). The mean
Constant Score at final follow-up was 81.5 (+/-14). 95.8% of patients were
satisfied of our treatment. According to SF-12 scores, we observed 44 (93.6%)
good results and 3 (6.4%) poor results. CONCLUSION: We suggest the use of MIKAI
KIT FEP(c) as a feasible option in the treatment of humeral shaft fractures. We
reported optimal clinical and radiological outcomes at long-term follow-up. We
advocate more powerful evidence to validate this new possible approach.
PMID- 28417291
TI - Reward Prediction Errors in Drug Addiction and Parkinson's Disease: from
Neurophysiology to Neuroimaging.
AB - PURPOSE OF REVIEW: Surprises are important sources of learning. Cognitive
scientists often refer to surprises as "reward prediction errors," a parameter
that captures discrepancies between expectations and actual outcomes. Here, we
integrate neurophysiological and functional magnetic resonance imaging (fMRI)
results addressing the processing of reward prediction errors and how they might
be altered in drug addiction and Parkinson's disease. RECENT FINDINGS: By
increasing phasic dopamine responses, drugs might accentuate prediction error
signals, causing increases in fMRI activity in mesolimbic areas in response to
drugs. Chronic substance dependence, by contrast, has been linked with
compromised dopaminergic function, which might be associated with blunted fMRI
responses to pleasant non-drug stimuli in mesocorticolimbic areas. In Parkinson's
disease, dopamine replacement therapies seem to induce impairments in learning
from negative outcomes. The present review provides a holistic overview of reward
prediction errors across different pathologies and might inform future clinical
strategies targeting impulsive/compulsive disorders.
PMID- 28417292
TI - Probiotic Strawberry Yogurts: Microbiological, Chemical and Sensory Properties.
AB - This study was performed to determine the viability of Lactobacillus acidophilus
and Bifidobacterium bifidum in yogurt made with strawberry marmalade (SM) and to
examine the quality properties of probiotic yogurt. Acidity, pH, bacterial counts
and sensory analysis of the yogurt samples were investigated on days 1, 3, 5, 7,
10 and 14 during storage at 4 degrees C. The survival rate of L. acidophilus was
greater than that of B. bifidum. The viability of L. acidophilus decreased during
the storage period, but B. bifidum numbers remained stable during the storage
period. The highest L. acidophilus count (7.20 log cfu/g) was found in L.
acidophilus + B. bifidum SM yogurt on day 1. The highest B. bifidum count (6.13
log cfu/g) was detected in yogurt containing L. acidophilus + B. bifidum SM
yogurt on day 7. Yeast and mould counts of all yogurts increased during the
storage period. Coliform bacteria and Staphylococcus aureus were not detected in
the yogurt samples. The highest overall acceptance sensory score was observed in
yogurts containing L. acidophilus. Considering the sensory and probiotic
characteristics of all yogurt samples, this study suggested that strawberry
yogurt with a suitable 5-7 day storage period can be produced with single L.
acidophilus addition or single B. bifidum addition.
PMID- 28417293
TI - Improvement of Geographic Disparities: Amelioration or Displacement?
AB - Progression of geographic disparities in social determinants of health is a
global concern. Using an Urban Health Index (UHI) approach, we proposed a
framework of examining the change of geographic disparities in social
determinants in small areas. Using the City of Atlanta in Georgia (USA) as a case
study, we standardized six census-based social determinant indicators in 2000 and
in 2010, respectively, and calculated their geometric mean to assign each census
tract a UHI value for 2000 and for 2010. We then evaluated the temporal change of
the UHIs in relation to the demographic changes using spatial and statistical
methods. We found that Atlanta experienced an improvement in social determinant
status and a reduction of disparities in the 10 years. The areas that experienced
improvement, however, underwent demographic changes as well. This analysis
provides support for displacement, rather than improvement, as the underlying
factor for apparent change in geographic disparities. Findings suggest the
importance of local evaluation for future policies to reduce disparities in
cities.
PMID- 28417294
TI - High trait shame undermines the protective effects of prevalence knowledge on
state shame following HPV/CIN diagnosis in women.
AB - Human papillomavirus (HPV), and the related, cervical intraepithelial neoplasia
(CIN), are common yet poorly understood physical conditions. The diagnosis of HPV
often elicits shame and guilt, which in turn may undermine psychological and
physical health. The current study compared shame and guilt responses to
diagnosis among two groups: women diagnosed with HPV/CIN and women diagnosed with
Epstein-Barr Virus (EBV/IM). Eighty women recently diagnosed with HPV/CIN or
EBV/IM completed measures of shame- and guilt-proneness, shame and guilt
following diagnosis, and disease knowledge including prevalence estimates (HPV
and EBV, respectively). HPV/CIN (vs. EBV/IM) predicted more diagnosis-related
shame and guilt. Estimates of high prevalence interacted with diagnosis and shame
proneness to predict diagnosis-related shame. Simple slope analyses indicated
that in women with HPV/CIN reporting low-to-average shame-proneness, high
prevalence estimates reduced diagnosis-related shame; however, women high in
shame-proneness experienced high diagnosis-related shame regardless of more
accurate prevalence estimates. Women high in shame-proneness appear to be
particularly vulnerable to HPV-related shame even when they are aware that it is
very common.
PMID- 28417295
TI - Drug-induced pulmonary arterial hypertension: a review.
AB - Pulmonary arterial hypertension (PAH) is a subgroup of PH patients characterized
hemodynamically by the presence of pre-capillary PH, defined by a pulmonary
artery wedge pressure (PAWP) <=15 mmHg and a PVR >3 Wood units (WU) in the
absence of other causes of pre-capillary PH. According to the current
classification, PAH can be associated with exposure to certain drugs or toxins
such as anorectic agents, amphetamines, or selective serotonin reuptake
inhibitors. With the improvement in awareness and recognition of the drug-induced
PAH, it allowed the identification of additional drugs associated with an
increased risk for the development of PAH. The supposed mechanism is an increase
in the serotonin levels or activation of serotonin receptors that has been
demonstrated to act as a growth factor for the pulmonary artery smooth muscle
cells and cause progressive obliteration of the pulmonary vasculature. PAH
remains a rare complication of several drugs, suggesting possible individual
susceptibility, and further studies are needed to identify patients at risk of
drug-induced PAH.
PMID- 28417296
TI - DPP4 inhibitors and cardiovascular outcomes: safety on heart failure.
AB - Diabetes is an important risk factor for cardiovascular disease. However,
clinical data suggests intensive glycemic control significantly increase rather
than decrease cardiovascular mortality, which is largely due to the fact that a
majority of oral anti-diabetic drugs have adverse cardiovascular effect. There
are several large-scale clinical trials evaluating the cardiovascular safety of
DPP4 inhibitors, a novel class of oral anti-diabetic medications, which have been
recently completed. They were proven to be safe with regard to cardiovascular
outcomes. However, concerns on the safety of heart failure have been raised as
the SAVOR-TIMI 53 trial reported a 27% increase in the risk for heart failure
hospitalization in diabetic patients treated with DPP4 inhibitor saxagliptin. In
this review, we will discuss recent advances in the heart failure effects of DPP4
inhibition and GLP-1 agonism.
PMID- 28417298
TI - Disseminated Mycobacterium malmoense and Salmonella Infections Associated with a
Novel Variant in NFKBIA.
PMID- 28417297
TI - Regulation of the glucose supply from capillary to tissue examined by developing
a capillary model.
AB - A new glucose transport model relying upon diffusion and convection across the
capillary membrane was developed, and supplemented with tissue space and lymph
flow. The rate of glucose utilization (J util) in the tissue space was described
as a saturation function of glucose concentration in the interstitial fluid (C
glu,isf), and was varied by applying a scaling factor f to J max. With f = 0, the
glucose diffusion ceased within ~20 min. While, with increasing f, the diffusion
was accelerated through a decrease in C glu,isf, but the convective flux remained
close to resting level. When the glucose supplying capacity of the capillary was
measured with a criterion of J util /J max = 0.5, the capacity increased in
proportion to the number of perfused capillaries. A consistent profile of
declining C glu,isf along the capillary axis was observed at the criterion of 0.5
irrespective of the capillary number. Increasing blood flow scarcely improved the
supplying capacity.
PMID- 28417299
TI - Negative prognostic effect of low nuclear GLI1 expression in glioblastomas.
AB - The hedgehog signaling plays supportive roles in various aspects of
tumorigenesis. Increased expression of the key component, GLI1, has been shown to
correlate with poor prognosis in many types of cancers. We aimed to investigate
the effect of GLI1 expression in glioblastoma focusing on the nuclear
localization. Immunohistochemistry for GLI1, GLI2, PTCH1, SMO, and SHH were done
in 140 glioblastoma tissues, and the staining was graded. For GLI1, nuclear and
cytoplasmic expression was separately assessed. No significant correlation was
found between clinicopathologic parameters and expression grades of the five
proteins. Low nuclear GLI1 expression was associated with a worse progression
free survival while overall survival was not significantly affected. In contrast,
cytoplasmic GLI1 expression did not have a prognostic effect. PTCH1 expression
correlated with nuclear GLI1 expression without exerting a significant prognostic
effect. Analysis of the TCGA-glioblastoma dataset revealed that low GLI1 mRNA
level also correlated with a poor prognosis for both overall and progression-free
survival. The adverse effect of low nuclear GLI1 expression in glioblastomas is
in contrast with the negative prognostic effect of high GLI1 expression reported
in non-cranial malignancies. The relative impact of hedgehog signaling among
other oncogenic pathways in the brain may be responsible for the difference. The
different implication of GLI1 expression in glioblastomas needs to be considered
in studies of hedgehog signaling-targeted therapy.
PMID- 28417301
TI - Overview of Coronary Heart Disease Risk Initiatives in South Asia.
AB - PURPOSE OF REVIEW: Cardiovascular disease (CVD) is now the leading cause of
morbidity and mortality worldwide. Industrialization and economic growth have led
to an unprecedented increment in the burden of CVD and their risk factors in less
industrialized regions of the world. While there are abundant data on CVD and
their risk factors from longitudinal cohort studies done in the West, good
quality data from South Asia are lacking. RECENT FINDINGS: Several multi
institutional, observational, prospective registries, and epidemiologic cohorts
in South Asia have been established to systematically evaluate the burden of CVD
and their risk factors. The PINNACLE (Practice Innovation and Clinical
Excellence) India Quality Improvement Program (PIQIP), the Kerala Acute Coronary
Syndrome (ACS), and Trivandrum Heart Failure registries have focused on secondary
prevention of CVD and performance measurement in both outpatient and inpatient
settings, respectively. The Prospective Urban and Rural Epidemiology (PURE),
Centre for Cardiometabolic Risk Reduction in South Asia (CARRS), and other
epidemiologic and genetic studies have focused on primary prevention of CVD and
evaluated variables such as environment, smoking, physical activity, health
systems, food and nutrition policy, dietary consumption patterns, socioeconomic
factors, and healthy neighborhoods. The international cardiovascular community
has been responsive to a burgeoning cardiovascular disease burden in South Asia.
Several collaborations have formed between the West (North America in particular)
and South Asia to catalyze evidence-based and data-driven changes in the federal
health policy in this part of the world to promote cardiovascular health and
mitigate cardiovascular risk.
PMID- 28417300
TI - A live gI/gE-deleted pseudorabies virus (PRV) protects weaned piglets against
lethal variant PRV challenge.
AB - Emerging pseudorabies virus (PRV) variant has led to frequent outbreaks of PRV
infection among Bartha-K61-vaccinated swine population in Chinese swine farms and
caused high mortality in pigs of all age since late 2011. Here, we generated a
gE/gI-deleted PRV (rPRVXJ-delgI/gE-EGFP) based on PRV variant strain (PRV-XJ)
through homologous DNA recombination. Compared to parental strain, rPRVXJ
delgI/gE-EGFP showed similar growth kinetics in vitro. Its safety and
immunogenicity were evaluated in weaned piglets. Our results showed that piglets
immunized with rPRVXJ-delgI/gE-EGFP did not exhibit any clinical symptoms, and a
high level of gB-specific antibody was detected. After lethal challenge with
variant PRV (PRV-FJ strain), all vaccinated piglets survived without showing any
clinical symptoms except slight fever within 7 days post-challenge. In
unvaccinated piglets, typical clinical symptoms of pseudorabies were observed,
and the piglets were all died at 5 days post-challenge. These results indicated
that a live rPRVXJ-delgI/gE-EGFP vaccine could be a maker vaccine candidate to
control the currently epidemic pseudorabies in China.
PMID- 28417303
TI - Paediatric in-patient prescribing errors in Malaysia: a cross-sectional
multicentre study.
AB - Background There is a lack of large comprehensive studies in developing countries
on paediatric in-patient prescribing errors in different settings. Objectives To
determine the characteristics of in-patient prescribing errors among paediatric
patients. Setting General paediatric wards, neonatal intensive care units and
paediatric intensive care units in government hospitals in Malaysia. Methods This
is a cross-sectional multicentre study involving 17 participating hospitals. Drug
charts were reviewed in each ward to identify the prescribing errors. All
prescribing errors identified were further assessed for their potential clinical
consequences, likely causes and contributing factors. Main outcome measures
Incidence, types, potential clinical consequences, causes and contributing
factors of the prescribing errors. Results The overall prescribing error rate was
9.2% out of 17,889 prescribed medications. There was no significant difference in
the prescribing error rates between different types of hospitals or wards. The
use of electronic prescribing had a higher prescribing error rate than manual
prescribing (16.9 vs 8.2%, p < 0.05). Twenty eight (1.7%) prescribing errors were
deemed to have serious potential clinical consequences and 2 (0.1%) were judged
to be potentially fatal. Most of the errors were attributed to human factors,
i.e. performance or knowledge deficit. The most common contributing factors were
due to lack of supervision or of knowledge. Conclusions Although electronic
prescribing may potentially improve safety, it may conversely cause prescribing
errors due to suboptimal interfaces and cumbersome work processes. Junior doctors
need specific training in paediatric prescribing and close supervision to reduce
prescribing errors in paediatric in-patients.
PMID- 28417304
TI - 2016 ASMS Workshop Review: Next Generation LC/MS: Critical Insights and Future
Perspectives.
PMID- 28417306
TI - A Focus Honoring R. Graham Cooks' Election to the National Academy of Sciences.
PMID- 28417305
TI - Uncovering Structural Diversity of Unsaturated Fatty Acyls in Cholesteryl Esters
via Photochemical Reaction and Tandem Mass Spectrometry.
AB - Mass spectrometry analysis of cholesteryl esters (CEs) faces several challenges,
with one of them being the determination of the carbon-carbon double bond (C=C)
locations within unsaturated fatty acyl chains. Patern?-Buchi (PB) reaction, a
photochemical reaction based on the addition of acetone to C=C, is capable of C=C
location determination when coupled with tandem mass spectrometry (MS/MS). In
this study, the PB reaction conditions were tailored for CEs and subsequent
nanoelectrospray ionization (nanoESI). A solvent system containing
acetone/methanol/dichloromethane/water (40/30/20/10, volume ratios) and 100 MUM
LiOH was determined to be optimal, resulting in reasonable PB reaction yield
(~30%) and good ionization efficiency (forming lithium adduct of CEs). Collision
induced dissociation (CID) of the PB reaction products produced characteristic
fragment ions of CE together with those modified by the PB reactions, such as
lithiated fatty acyl ([FA + Li]+) and its PB product ([FA - PB + Li]+). MS3 CID
of [FA - PB + Li]+ led to abundant C=C diagnostic ion formation, which was used
for C=C location determination and isomer quantitation. A PB-MS3 CID approach was
developed and applied for CE analysis from human plasma. A series of unsaturated
CEs was identified with specific C=C locations within fatty acyl chains. Absolute
quantitation for each CE species was achieved including coexisting C=C location
isomers, such as Delta9 and Delta11 isomers of CE 18:1 and omega-6 and omega-3
isomers of CE 18:3. These results show that PB-MS/MS is useful in uncovering
structural diversity of CEs due to unsaturation in fatty acyls, which is often
undetected from current lipid analysis approach. Graphical Abstract ?.
PMID- 28417307
TI - Investigating Differences in Gas-Phase Conformations of 25-Hydroxyvitamin D3
Sodiated Epimers using Ion Mobility-Mass Spectrometry and Theoretical Modeling.
AB - Drift tube ion mobility coupled with mass spectrometry was used to investigate
the gas-phase structure of 25-hydroxyvitamin D3 (25OHD3) and D2 (25OHD2) epimers,
and to evaluate its potential in rapid separation of these compounds.
Experimental results revealed two distinct drift species for the 25OHD3 sodiated
monomer, whereas only one of these conformations was observed for its epimer
(epi25OHD3). The unique species allowed 25OHD3 to be readily distinguished, and
the same pattern was observed for 25OHD2 epimers. Theoretical modeling of 25OHD3
epimers identified energetically stable gas-phase structures, indicating that
both compounds may adopt a compact "closed" conformation, but that 25OHD3 may
also adopt a slightly less energetically favorable "open" conformation that is
not accessible to its epimer. Calculated theoretical collision cross-sections for
these structures agreed with experimental results to <2%. Experimentation
indicated that additional energy in the ESI source (i.e., increased temperature,
spray voltage) affected the ratio of 25OHD3 conformations, with the less
energetically favorable "open" conformation increasing in relative intensity.
Finally, LC-IM-MS results yielded linear quantitation of 25OHD3, in the presence
of the epimer interference, at biologically relevant concentrations. This study
demonstrates that ion mobility can be used in tandem with theoretical modeling to
determine structural differences that contribute to drift separation. These
separation capabilities provide potential for rapid (<60 ms) identification of
25OHD3 and 25OHD2 in mixtures with their epimers. Graphical Abstract ?.
PMID- 28417308
TI - Treatment of menstrual migraine; multidisciplinary or mono-disciplinary approach.
AB - BACKGROUND: The aim of this study was to compare a multidisciplinary approach of
menstrual (related) migraine, combining the neurological and gynaecological
consultation, to a mono-disciplinary approach involving neurological treatment.
There is a clear relationship between the menstruation cycle and the occurrence
of migraine (menstrual migraine). Nowadays the treatment of menstrual (related)
migraine is performed by a neurologist. A treatment with attention to hormonal
treatment seems more convenient. METHODS: This retrospective study was performed
in a cohort using data of 88 women with menstrual (related) migraine who visited
the menstrual migraine clinic between 2012 and 2014 (intervention group). The
results were compared to a historical control group, which consisted of women
with menstrual (related) migraine who were treated before 2012 and received a
mono-disciplinary approach. RESULTS: In the intervention group the Headache
Impact (HIT) score significantly improved (65 to 59 points). The mean headache
days per month declined significantly (from 6 to 3.83 days) and these women
needed less use of pain medication. In the control group the decline in HIT score
was less striking (65 to 63.5 points) and the mean headache days per month
increased (6 to 6,5 days). It appeared that 20 out of 27 patients in the control
group required a gynaecological consultation in course of time. CONCLUSION: A
multidisicplinary treatment of women with menstrual (related) migraine gives
better results compared to a mono-disciplinary approach. These results should be
interpreted with caution as we performed a retrospective study with a relative
small control group.
PMID- 28417309
TI - Effects of Nano-zinc on Biochemical Parameters in Cadmium-Exposed Rats.
AB - Cadmium (Cd) is a toxic environmental and occupational pollutant with reported
toxic effects on the kidneys, liver, lungs, bones, and the immunity system. Based
on its physicochemical similarity to cadmium, zinc (Zn) shows protective effects
against cadmium toxicity and cadmium accumulation in the body. Nano-zinc and nano
zinc oxide (ZnO), recently used in foods and pharmaceutical products, can release
a great amount of Zn2+ in their environment. This research was carried out to
investigate the more potent properties of the metal zinc among sub-acute cadmium
intoxicated rats. Seventy-five male Wistar rats were caged in 15 groups. Cadmium
chloride (CdCl2) was used in drinking water to induce cadmium toxicity. Different
sizes (15, 20, and 30 nm) and doses of nano-zinc particles (3, 10, 100 mg/kg body
weight [bw]) were administered solely and simultaneously with CdCl2 (2-5 mg/kg
bw) for 28 days. The experimental animals were decapitated, and the biochemical
biomarkers (enzymatic and non-enzymatic) were determined in their serum after
oral exposure to nano-zinc and cadmium. Statistical analysis was carried out with
a one-way ANOVA and t test. P < 0.05 was considered as statistically significant.
The haematocrit (HCT) significantly increased and blood coagulation time
significantly reduced in the nano-zinc-treated rats. AST, ALT, triglyceride,
total cholesterol, LDL, and free fatty acids increased significantly in the
cadmium- and nano-zinc-treated rats compared with the controls. However, albumin,
total protein, and HDLc significantly decreased in the cadmium- and nano-zinc
treated rats compared with the controls (P < 0.05). It seems that in the oral
administration of nano-zinc, the smaller sizes with low doses and the larger
sizes with high doses are more toxic than metallic zinc. In a few cases, an
inverse dose-dependent relationship was seen as well. This research showed that
in spite of larger sizes of zinc, smaller sizes of nano-zinc particles are not
suitable for protection against cadmium intoxication.
PMID- 28417310
TI - Telemedicine and Palliative Care: an Increasing Role in Supportive Oncology.
AB - With the emergence of telemedicine as a routine form of care in various venues,
the opportunities to use technology to care for the most vulnerable, most ill
cancer patients are extremely appealing. Increasingly, evidence supports early
integration of palliative care with standard oncologic care, supported by recent
NCCN guidelines to increase and improve access to palliative care. This review
looks at the use of telemedicine to expand access to palliative care as well as
provide better care for patients and families where travel is difficult, if not
impossible. When telemedicine has been used, often in Europe, for palliative
care, the results show improvements in symptom management, comfort with care as
well as patient and family satisfaction. One barrier to use of telemedicine is
the concerns with technology and technology-related complications in population
that is often elderly, frail and not always comfortable with non-face-to-face
physician care. There remain significant opportunities to explore this
intersection of supportive care and telemedicine.
PMID- 28417312
TI - The need for national registries for rare endocrine tumor syndromes.
PMID- 28417311
TI - Immune Checkpoint Inhibitors for Brain Metastases.
AB - PURPOSE OF REVIEW: Metastasis of cancer to the brain typically portends a poor
prognosis and often results in significant morbidity, including from the side
effects of treatment. More effective therapies for patients with brain metastases
are needed. The current treatment paradigm uses multiple modalities, including
surgery, radiation, and in some contexts, systemic chemotherapy and
immunotherapy. Immune checkpoint inhibitors are increasingly being used to treat
extracranial disease, and their effectiveness in the management of brain
metastases needs to be understood. RECENT FINDINGS: The evidence for immune
checkpoint inhibitors in the management of brain metastases is largely limited to
retrospective analyses of melanoma metastases and ipilimumab. Prospective
clinical trials of more active agents are under way, and tentative results
suggest activity. Immune checkpoint inhibitors have the potential to improve
outcomes in patients with brain metastases. Results of current clinical trials
will aid in determining the appropriate sequence or combination of local and
systemic therapies.
PMID- 28417313
TI - Impact of season and different vitamin D thresholds on prevalence of vitamin D
deficiency in epidemiological cohorts-a note of caution.
AB - PURPOSE: We investigated the impact of different cut-offs on the prevalence of 25
hydroxyvitamin D [25-(OH)D] deficiency. METHODS: We used baseline data of 4149
participants (45-75 years, 50% women) of the population-based Heinz Nixdorf
Recall study. Serum 25-(OH)D was measured with the Roche Cobas assay. Quartiles
(p25, p50, and p75) were calculated. Data were stratified by months, sex, and
age. According to the recommendations of 'Dachverband Osteologie', Endocrine
Society and National Institute of Health we used 25-(OH)D thresholds of 12, 20,
and 30 ng/ml to estimate vitamin D deficiency. RESULTS: Overall the median of 25
(OH)D was 19.8 ng/ml (p25 = 14.4 ng/ml, p75 = 26.6 ng/ml), with highest
concentrations in July (p50 = 23.8 ng/ml, p25 = 18.2 ng/ml, and p75 = 31.2 ng/ml)
and lowest in March (p50 = 15.8 ng/ml, p25 = 11.5 ng/ml, and p75 = 20.6 ng/ml).
Prevalence of vitamin D deficiency rose from 16, 51 up to 83% using the cut-offs
of <12, <20 ng/ml, and <30 ng/ml, respectively. With respect to seasonal
variance, prevalence of vitamin D deficiency rose to 92% in February/March using
the cut-off <30 ng/ml (<12: 28%, <20 ng/ml: 71%) whereas in June/July prevalence
of vitamin D deficiency decreased to 71% (<12: 6%, <20 ng/ml: 30%). The chance to
attest the diagnosis of vitamin D deficiency for cut-off 12 ng/ml in March is 6.4
fold higher than in June, for cut-off 20 ng/ml, 5.5-fold higher and for cut-off
30 ng/ml, 3.1-fold higher. CONCLUSIONS: Guidelines to define vitamin D deficiency
revealed extremely different prevalence rates ranging between 6 and 92%.
Accounting for collection time and antecedent sun exposure are important to
reduce bias in research studies and improve decision-making in clinical care.
Vitamin D thresholds have to be rethought.
PMID- 28417314
TI - Prognostic factors for gastroenteropancreatic neuroendocrine neoplasms (GEP
NENs): what's better?
PMID- 28417316
TI - A Web Resource for Levodopa-Induced Dyskinesia Genetics in Parkinson's Disease.
PMID- 28417315
TI - Disruption of Energy Transfer and Redox Status by Sulfite in Hippocampus,
Striatum, and Cerebellum of Developing Rats.
AB - Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities,
whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite
and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase
(CK) activity, mitochondrial respiration and redox status in hippocampus,
striatum and cerebellum of developing rats. Our in vitro results showed that
sulfite and thiosulfate decreased CK activity, whereas sulfite also increased
malondialdehyde (MDA) levels in all brain structures evaluated. Sulfite further
diminished mitochondrial respiration and increased DCFH oxidation and hydrogen
peroxide production in hippocampus. Sulfite-induced CK activity decrease was
prevented by melatonin (MEL), resveratrol (RSV), and dithiothreitol while
increase of MDA levels was prevented by MEL and RSV. Regarding the antioxidant
system, sulfite increased glutathione concentrations in hippocampus and striatum.
In addition, sulfite decreased the activities of glutathione peroxidase in all
brain structures, of glutathione S-transferase in hippocampus and cerebellum, and
of glutathione reductase in cerebellum. In vivo experiments performed with
intrahippocampal administration of sulfite demonstrated that this metabolite
increased superoxide dismutase activity without altering other biochemical
parameters in rat hippocampus. Our data suggest that impairment of energy
metabolism and redox status may be important pathomechanisms involved in brain
damage observed in individuals with SO deficiency.
PMID- 28417317
TI - Erratum to: The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in
nAMD: Systematic Review and Network Meta-Analysis.
PMID- 28417318
TI - Patient and Healthcare Professionals Preference for Brenzys vs. Enbrel
Autoinjector for Rheumatoid Arthritis: A Randomized Crossover Simulated-Use
Study.
AB - INTRODUCTION: Brenzys was developed as an etanercept biosimilar of Enbrel. The
aim of this study was to assess preference and perceived ease of use for the new
Brenzys autoinjector compared to the currently available marketed Enbrel MYCLIC
autoinjector (Australia) and Enbrel SureClick autoinjector (Canada) for the
treatment of rheumatoid arthritis (RA). Because RA affects manual dexterity, ease
of use of an autoinjector is a particularly important consideration in developing
effective self-delivery of long-term courses of therapy. METHODS: Patients (N =
191) reporting a diagnosis of RA and nurses and rheumatologists (N = 90) with
experience managing RA were shown how to use Brenzys and Enbrel autoinjectors (in
counterbalanced order between participants), then they used each autoinjector by
injecting into a pad simulating skin, and completed a questionnaire. Study
sessions took place in Australia and Canada. RESULTS: A binomial test showed that
significantly more patients indicated that the Brenzys autoinjector was easier to
use than the Enbrel autoinjector (79% reporting Brenzys easier to use; p < 0.001,
two-sided, 95% CI [73%, 85%]). In addition, significantly more nurses and
rheumatologists with experience managing RA also indicated that the Brenzys
autoinjector was easier to use (86%; p < 0.001, two-sided, 95% CI [77%, 92%) and
that they would recommend the buttonless Brenzys autoinjector over the Enbrel
autoinjector to patients (83%; p < 0.001, two-sided, 95% CI [74%, 90%]). Almost
all patients who reported past experience using an Enbrel autoinjector (N = 17)
reported on the basis of using the two devices in the study that they would
prefer to switch their device to the Brenzys autoinjector rather than continue
their course of therapy using the Enbrel autoinjector (16/17, 94%, 95% CI [71%,
100%]). CONCLUSION: On the basis of the study results, the Brenzys autoinjector
was rated statistically significantly easier to use, and was overall preferred by
patients and healthcare professionals with experience managing RA patients.
FUNDING: Merck & Co., Inc.
PMID- 28417319
TI - Cognitive Function and Vascular Risk Factors Among Older African American Adults.
AB - To evaluate the association between vascular risk factors and cognitive
impairment among older African American (AA) adults in a primary care clinic.
Participants included 96 AA adults aged 60 years or older who were evaluated for
global and domain-specific cognition. Participants were interviewed using the
Computerized Assessment of Memory and Cognitive Impairment (CAMCI). The
relationship between CAMCI cognitive domain scores and vascular risk factors were
examined using hierarchical regression models. Patients who smoked, those with
higher SBP/DBP values had lower accuracy rates on CAMCI cognitive domains
(attention, executive, memory).Those with higher BMI had better attention scores.
Patients with higher HbA1C values had worse verbal memory. Patients with higher
blood pressure were significantly faster in responding to tasks in the executive
domain. Primary care providers working with older AA adults with these VRFs could
implement cognitive screening earlier into their practice to reduce barriers of
seeking treatment.
PMID- 28417320
TI - Patient Reporting in the EU: Analysis of EudraVigilance Data.
AB - INTRODUCTION: New pharmacovigilance legislation was adopted in the EU in 2010 and
became operational in July 2012. The legislation placed an obligation on all
national competent authorities (NCAs) and marketing authorisation holders (MAHs)
to record and report cases of suspected adverse drug reactions (ADRs) received
from patients. OBJECTIVES: This descriptive study aims to provide insight into
patient reporting for the totality of the EU by querying the EudraVigilance (EV)
database for the period of 3 years before the new pharmacovigilance legislation
became operational and the 3 years after as well as comparing patient reports
with those from healthcare professionals (HCPs) where feasible. METHODS: We
queried the EV database for the following characteristics of patient and HCP
reports: demographics (patient sex and age), seriousness, reported ADR terms,
reported indications, number of ADRs per report, time to report an ADR, and most
reported substances. Wherever feasible, direct comparisons between patient
reports and HCP reports were performed using relative risks. RESULTS: The EV
database contained a total of 53,130 patient reports in the 3 years preceding the
legislation operation period and 113,371 in the 3 years after. Member states
contributing the most patient reports to the EV database were the Netherlands,
the UK, Germany, France and Italy. The results for indications and substances
show that patients were more likely than HCPs to report for genitourinary,
hormonal and reproductive indications. Patients reported more in general
disorders and administration site conditions Medical Dictionary for Regulatory
Activities (MedDRA) System Organ Class (SOC), whereas HCPs reported more
Preferred Terms (PTs) belonging in the Investigations SOC. However, 13 of the 20
reactions most frequently reported by patients were also among the top 20
reactions reported by HCPs. CONCLUSION: Patient reporting complemented reporting
by HCPs. Patients were motivated to report ADRs, especially those that affected
their quality of life. Sharing these results with NCAs and patient associations
can inform training and awareness on patient reporting.
PMID- 28417321
TI - Adjuvanted (AS03) A/H1N1 2009 Pandemic Influenza Vaccines and Solid Organ
Transplant Rejection: Systematic Signal Evaluation and Lessons Learnt.
AB - INTRODUCTION: We investigated a signal of solid organ transplant (SOT) rejection
after immunisation with (AS03) A/H1N1 2009 pandemic influenza vaccines. METHODS:
Potential immunological mechanisms were reviewed and quantitative analyses were
conducted. The feasibility of pharmacoepidemiological studies was explored.
RESULTS: Overall results, including data from a pharmacoepidemiological study,
support the safety of adjuvanted (AS03) pandemic influenza vaccination in SOT
recipients. The regulatory commitment to evaluate the signal through a stepwise
investigation was closed in 2014. CONCLUSION: Lessons learned highlight the
importance of investigating plausible biological mechanisms between vaccines and
potentially associated adverse outcomes, and the importance of selecting
appropriate study settings and designs for safety signal investigations.
PMID- 28417322
TI - Are midge swarms bound together by an effective velocity-dependent gravity?
AB - Midge swarms are a canonical example of collective animal behaviour where local
interactions do not clearly play a major role and yet the animals display group
level cohesion. The midges appear somewhat paradoxically to be tightly bound to
the swarm whilst at the same time weakly coupled inside it. The microscopic
origins of this behaviour have remained elusive. Models based on Newtonian
gravity do, however, agree well with experimental observations of laboratory
swarms. They are biologically plausible since gravitational interactions have
similitude with long-range acoustic and visual interactions, and they correctly
predict that individual attraction to the swarm centre increases linearly with
distance from the swarm centre. Here we show that the observed kinematics implies
that this attraction also increases with an individual's flight speed. We find
clear evidence for such an attractive force in experimental data.
PMID- 28417323
TI - Polymer chain collapse induced by many-body dipole correlations.
AB - We present a simple analytical theory of a flexible polymer chain dissolved in a
good solvent, carrying permanent freely oriented dipoles on the monomers. We take
into account the dipole correlations within the random phase approximation (RPA),
as well as a dielectric heterogeneity in the internal polymer volume relative to
the bulk solution. We demonstrate that the dipole correlations of monomers can be
taken into account as pairwise ones only when the polymer chain is in a coil
conformation. In this case the dipole correlations manifest themselves through
the Keesom interactions of the permanent dipoles. On the other hand, the
dielectric heterogeneity effect (dielectric mismatch effect) leads to the
effective interaction between the monomers of the polymeric coil. Both of these
effects can be taken into account by renormalizing the second virial coefficient
of the monomer-monomer volume interactions. We establish that in the case when
the solvent dielectric permittivity exceeds the dielectric permittivity of the
polymeric material, the dielectric mismatch effect competes with the dipole
attractive interactions, leading to polymer coil expansion. In the opposite case,
both the dielectric mismatch effect and the dipole attractive interaction lead to
the polymer coil collapse. We analyse the coil-globule transition caused by the
dipole correlations of monomers within the many-body theory. We demonstrate that
accounting for the dipole correlations higher than the pairwise ones smooths this
pure electrostatics driven coil-globule transition of the polymer chain.
PMID- 28417324
TI - Current remote sensing approaches to monitoring forest degradation in support of
countries measurement, reporting and verification (MRV) systems for REDD.
AB - Forest degradation is a global phenomenon and while being an important indicator
and precursor to further forest loss, carbon emissions due to degradation should
also be accounted for in national reporting within the frame of UN REDD+. At
regional to country scales, methods have been progressively developed to detect
and map forest degradation, with these based on multi-resolution optical,
synthetic aperture radar (SAR) and/or LiDAR data. However, there is no one single
method that can be applied to monitor forest degradation, largely due to the
specific nature of the degradation type or process and the timeframe over which
it is observed. The review assesses two main approaches to monitoring forest
degradation: first, where detection is indicated by a change in canopy cover or
proxies, and second, the quantification of loss (or gain) in above ground biomass
(AGB). The discussion only considers degradation that has a visible impact on the
forest canopy and is thus detectable by remote sensing. The first approach
encompasses methods that characterise the type of degradation and track
disturbance, detect gaps in, and fragmentation of, the forest canopy, and proxies
that provide evidence of forestry activity. Progress in these topics has seen the
extension of methods to higher resolution (both spatial and temporal) data to
better capture the disturbance signal, distinguish degraded and intact forest,
and monitor regrowth. Improvements in the reliability of mapping methods are
anticipated by SAR-optical data fusion and use of very high resolution data. The
second approach exploits EO sensors with known sensitivity to forest structure
and biomass and discusses monitoring efforts using repeat LiDAR and SAR data.
There has been progress in the capacity to discriminate forest age and growth
stage using data fusion methods and LiDAR height metrics. Interferometric SAR and
LiDAR have found new application in linking forest structure change to
degradation in tropical forests. Estimates of AGB change have been demonstrated
at national level using SAR and LiDAR-assisted approaches. Future improvements
are anticipated with the availability of next generation LiDAR sensors. Improved
access to relevant satellite data and best available methods are key to
operational forest degradation monitoring. Countries will need to prioritise
their monitoring efforts depending on the significance of the degradation,
balanced against available resources. A better understanding of the drivers and
impacts of degradation will help guide monitoring and restoration efforts.
Ultimately we want to restore ecosystem service and function in degraded forests
before the change is irreversible.
PMID- 28417325
TI - Microscopic and spectroscopic characterization of humic substances from a compost
amended copper contaminated soil: main features and their potential effects on Cu
immobilization.
AB - We characterized humic substances (HS) extracted from a Cu-contaminated soil
without compost addition (C) or amended with a wheat straw-based compost (WSC)
(H1), co-composted with Fe2O3 (H2), or co-composted with an allophane-rich soil
(H3). Extracted HS were characterized under electron microscopy (SEM/TEM), energy
dispersive X-ray (X-EDS), and Fourier transform infrared (FTIR) spectroscopy. In
addition, HS extracted from WSC (H4) were characterized at pH 4.0 and 8.0 with
descriptive purposes. At pH 4.0, globular structures of H4 were observed, some of
them aggregating within a large network. Contrariwise, at pH 8.0, long tubular
and disaggregated structures prevailed. TEM microscopy suggests organo-mineral
interactions at scales of 1 to 200 nm with iron oxide nanoparticles. HS extracted
from soil-compost incubations showed interactions at nanoscale with minerals and
crystal compounds into the organic matrix of HS. Bands associated to acidic
functional groups of HS may suggest potential sorption interactions with
transition metals. We conclude that metal ions and pH have an important role
controlling the morphology and configuration of HS from WSC. Characterization of
H4 extracted from WSC showed that physicochemical protection of HS could be
present in composting systems treated with inorganic materials. Finally, the
humified fractions obtained from compost-amended soils may have an important
effect on metal-retention, supporting their potential use in metal-contaminated
soils.
PMID- 28417326
TI - A time series analysis of environmental and metrological factors impact on
cutaneous leishmaniasis incidence in an endemic area of Dehloran, Iran.
AB - The aim of this study was to investigate the relationship between the
environmental and metrological variables and cutaneous leishmaniasis (CL)
transmission and its prediction in a region susceptible to this disease
prevalence using a time series model. The accurate locations of 4437 CL diagnosed
from 2011 to 2015 were obtained to be used in the time series model. Temperature,
number of days with temperature over 30 degrees C, and number of earthquake were
related to CL incidence using the Seasonal Auto-correlated Integrated Moving
Average (SARIMA) model according to the Box-Jenkins method. In addition, the
relationship between land use and surface soil type in 500- and 1000-m radius
around the CL patients were investigated. The SARIMA models showed significant
associations between environmental and meteorological variables and CL incidence
adjusted for seasonality and auto-correlation. The result indicated that there
are need more robust preventive programs in earthquake-prone areas with high
temperature and inceptisol soil type than other areas. In addition, the region
with these characteristics should be considered as high-risk areas for CL
prevalence.
PMID- 28417327
TI - Influence of land use and land cover on the spatial variability of dissolved
organic matter in multiple aquatic environments.
AB - Water quality of lakes, estuaries, and coastal areas serves as an indicator of
the overall health of aquatic ecosystems as well as the health of the terrestrial
ecosystem that drains to the water body. Land use and land cover plays not only a
significant role in controlling the quantity of the exported dissolved organic
matter (DOM) but also influences the quality of DOM via various biogeochemical
and biodegradation processes. We examined the characteristics and spatial
distribution of DOM in five major lakes, in an estuary, and in the coastal waters
of the Mississippi, USA, and investigated the influence of the land use and land
cover of their watersheds on the DOM composition. We employed absorption and
fluorescence spectroscopy including excitation-emission matrix (EEM) combined
with parallel factor (PARAFAC) analysis modeling techniques to determine optical
properties of DOM and its characteristics in this study. We developed a site
specific PARAFAC model to evaluate DOM characteristics resulting in five diverse
DOM compositions that included two terrestrial humic-like (C1 and C3), two
microbial humic-like (C2 and C5), and one protein-like (C4) DOM. Our results
showed elevated fluorescence levels of microbial humic-like or protein-like DOM
in the lakes and coastal waters, while the estuarine waters showed relatively
high fluorescence levels of terrestrial humic-like DOM. The results also showed
that percent forest and wetland coverage explained 68 and 82% variability,
respectively, in terrestrial humic-like DOM exports, while 87% variability in
microbially derived humiclike DOM was explained by percent agricultural lands.
Strong correlations between microbial humic-like DOM and fluorescence-derived DOM
indices such as biological index (BIX) and fluorescence index (FI) indicated
autochthonous characteristics in the lakes, while the estuary showed largely
allochthonous DOM of terrestrial origin. We also observed higher concentrations
of total dissolved phosphorous (TDP) and ammonium nitrogen (NH4-N) in coastal
waters potentially due to photodegradation of refractory DOM derived from the
sediment-bound organic matter in the coastal wetlands. This study highlights the
relationships between the DOM compositions in the water and the land use and land
cover in the watershed. The spatial variability of DOM in three different types
of aquatic environments enhances the understanding of the role of land use and
land cover in carbon cycling through export of organic matter to the aquatic
ecosystems..
PMID- 28417328
TI - Characterization and pyrolysis of Chlorella vulgaris and Arthrospira platensis:
potential of bio-oil and chemical production by Py-GC/MS analysis.
AB - Biofuels have been seen as potential sources to meet future energy demand as a
renewable and sustainable energy source. Despite the fact that the production
technology of first-generation biofuels is consolidated, these biofuels are
produced from foods crops such as grains, sugar cane, and vegetable oils
competing with food for crop use and agricultural land. In recent years, it was
found that microalgae have the potential to provide a viable alternative to
fossil fuels as source of biofuels without compromising food supplies or arable
land. On this scenario, this paper aims to demonstrate the energetic potential to
produce bio-oil and chemicals from microalgae Chlorella vulgaris and Arthrospira
platensis. The potential of these biomasses was evaluated in terms of physical
chemical characterization, thermogravimetric analysis, and analytical pyrolysis
interfaced with gas chromatograph (Py-GC/MS). The results show that C. vulgaris
and A. platensis are biomasses with a high heating value (24.60 and 22.43 MJ/kg)
and low ash content, showing a high percentage of volatile matter (72.49 and
79.42%). These characteristics confirm their energetic potential for conversion
process through pyrolysis, whereby some important aromatic compounds such as
toluene, styrene, and phenol were identified as pyrolysis products, which could
turn these microalgae a potential for biofuels and bioproduct production through
the pyrolysis.
PMID- 28417329
TI - Quantitative cancer risk assessment and local mortality burden for ambient air
pollution in an eastern Mediterranean City.
AB - Health risks posed by ambient air pollutants to the urban Lebanese population
have not been well characterized. The aim of this study is to assess cancer risk
and mortality burden of non-methane hydrocarbons (NMHCs) and particulates (PM)
based on two field-sampling campaigns conducted during summer and winter seasons
in Beirut. Seventy NMHCs were analyzed by TD-GC-FID. PM2.5 elemental carbon (EC)
components were examined using a Lab OC-EC aerosol Analyzer, and polycyclic
aromatic hydrocarbons were analyzed by GC-MS. The US EPA fraction-based approach
was used to assess non-cancer hazard and cancer risk for the hydrocarbon mixture,
and the UK Committee on Medical Effects of Air Pollutants (COMEAP) guidelines
were followed to determine the PM2.5 attributable mortality burden. The average
cumulative cancer risk exceeded the US EPA acceptable level (10-6) by 40-fold in
the summer and 30-fold in the winter. Benzene was found to be the highest
contributor to cancer risk (39-43%), followed by 1,3-butadiene (25-29%), both
originating from traffic gasoline evaporation and combustion. The EC attributable
average mortality fraction was 7.8-10%, while the average attributable number of
deaths (AD) and years of life lost (YLL) were found to be 257-327 and 3086-3923,
respectively. Our findings provide a baseline for future air monitoring programs,
and for interventions aiming at reducing cancer risk in this population.
PMID- 28417330
TI - Management of Nasal Fractures in Sports.
AB - Nasal fractures represent approximately 60% of all maxillofacial injuries that
occur in athletic activities; however, there are no current guidelines regarding
immediate sideline management of these injuries. Therefore, the purpose of this
article was to (1) summarize the anatomy, etiology, and incidence of nasal
fractures, and (2) evaluate the current body of literature regarding immediate on
field and subsequent outpatient management. It is imperative to establish that
the athlete's airway is not compromised and there are no other severe concomitant
injuries, such as a concussion, ocular injury, or leakage of cerebrospinal fluid.
Immediate closed reduction should not be attempted unless there is airway
compromise or the practitioner has experience in performing it. The majority of
athletes with these injuries in isolation may return to play; however, in our
practice, we recommend they wear a face mask for 6 weeks after their injury.
Despite our recommendations, we know there is a paucity of clinical studies on
immediate sideline and longer-term management. Future studies should focus on
establishing therapeutic algorithms that will allow physicians to make treatment
recommendations to patients with strong evidence to support their decision.
PMID- 28417331
TI - Use of High-Dose Oral Valacyclovir During an Intravenous Acyclovir Shortage: A
Retrospective Analysis of Tolerability and Drug Shortage Management.
AB - INTRODUCTION: In late 2011, a shortage of IV acyclovir led to the need to
empirically substitute high-dose oral valacyclovir (HDVA) to conserve IV
acyclovir for patients with confirmed herpes simplex virus (HSV) meningitis or
encephalitis. This report describes the management of the most recent national IV
acyclovir shortage by the Antimicrobial Stewardship Program (ASP) at Northwestern
Memorial Hospital (NMH), Chicago, IL, USA, and the use of HDVA. Secondarily, we
assessed the safety and tolerability of HDVA as an alternate to IV acyclovir
during this shortage. METHODS: We report the step-wise management, restrictions,
and guidelines implemented at NMH during a protracted IV acyclovir shortage. The
assessment of HDVA was a retrospective, observational cohort study of
hospitalized patients receiving HDVA between 1 January 2012 and 31 December 2013.
Appropriate demographic and treatment variables were collected. The primary
outcome was percentage of patients experiencing an adverse event. RESULTS: There
were 15 adult patients included in the study on a median daily dose of HDVA of 3
g (IQR 2-8). There were four patients with microbiologically confirmed viral CNS
infections (n = 1 HSV-1, n = 2 HSV-2, n = 1 VZV encephalitis) and eleven patients
with unknown causative pathogens. Six (40%) patients experienced at least one
adverse drug reaction (ADR) to HDVA (thrombocytopenia, 33.3%, n = 5; headache,
6.7%, n = 1; nausea, 6.7%, n = 1; rash, 6.7%, n = 1). One patient (6.7%) was
readmitted within 30 days with a suspected non-CNS infection. There were no
treatment discontinuations or symptomatic therapy necessary to treat any of the
ADRs. CONCLUSIONS: The shortage of IV acyclovir was successfully managed by the
ASP and HDVA appeared to be well tolerated when used as an alternative to IV
acyclovir.
PMID- 28417332
TI - Assessment of the prognostic and discriminating value of the novel bioscore
system for breast cancer; a SEER database analysis.
AB - BACKGROUND: An updated bioscore has been proposed within the context of the 8th
edition American Joint Committee on Cancer (AJCC) staging system for breast
cancer. This study seeks to validate the discriminating value of this bioscore
among non-metastatic breast cancer patients registered within the surveillance,
epidemiology, and end results (SEER) database. METHODS: Through SEER*Stat
program, SEER database (2010-2013) was accessed and bioscore was formulated for
each patient. Overall and cancer-specific survival analyses according to both
bioscore and AJCC pathological stages were conducted through Kaplan-Meier
analysis/log-rank testing, and multivariate analysis was conducted through a Cox
proportional model. RESULTS: A total of 181030 patients with non-metastatic,
surgically treated breast cancer were identified in the period from 2010 to 2013.
For overall and cancer-specific survival assessment according to the bioscore
system, P values for pairwise comparisons among different score points were
significant (P < 0.0001) except for the comparison between score 0 and score 1.
For cancer-specific survival assessment according to the AJCC stages, P values
for pairwise comparisons among different stages were significant (P < 0.0001)
except for the comparison between stages IIIB and IIIC. For overall survival
assessment according to the AJCC stages, P values for pairwise comparisons among
different stages were significant (P < 0.001) except for the comparison between
stages IA and IB. In a multivariate analysis, the following factors were
associated with better cancer-specific survival (earlier stage disease, ER
positivity, PR positivity, Her2 neu positivity, and nuclear grade) (P < 0.0001).
CONCLUSION: The current analysis confirms the prognostic utility of the bioscore
system and suggests it may be incorporated into decision-making algorithms for
non-metastatic breast cancer.
PMID- 28417333
TI - Immediate tissue expander or implant-based breast reconstruction does not
compromise the oncologic delivery of post-mastectomy radiotherapy (PMRT).
AB - PURPOSE: Increasingly, women are choosing immediate breast reconstruction (IBR)
following mastectomy. Reports have indicated IBR may compromise post-mastectomy
radiotherapy (PMRT). We investigated the impact of IBR on timing of PMRT, target
coverage, and doses to organs at risk in a modern radiotherapy practice using
advanced planning techniques. METHODS: Between 2013 and 2015, PMRT was delivered
to 116 patients (66 mastectomy alone, 50 IBR). PMRT was delivered with a median
dose of 50 Gy in 25 fractions. Left-sided patients were treated in breath-hold
under image guidance. Differences in dosimetric parameters and time to the
initiation of PMRT were assessed between patients with and without
reconstruction. RESULTS: Reconstructed patients were younger and had lower
clinical stage disease. Reconstruction did not significantly increase the mean
time to PMRT initiation (51 days reconstructed vs. 45 days non-reconstructed, p =
0.14) or the number of patients who initiated PMRT within 12 weeks of the last
therapeutic intervention (48/50 [96.0] vs. 61/66 [92.4%], p = 0.41). There was no
significant difference in the percentage of patients in whom the internal mammary
lymph nodes (IMNs) were targeted (72 vs. 80%, p = 0.29) or in IMN target coverage
(mean IMN V40.5 Gy 92.6 vs. 94.1%, p = 0.62). Reconstruction did not
significantly affect the mean ipsilateral lung V20 (25.4 vs. 26.4%, p = 0.37) or
the mean heart dose (2.2 vs. 2.1 Gy, p = 0.63). CONCLUSIONS: In a specialized
breast multidisciplinary practice, immediate breast reconstruction did not
significantly delay PMRT, compromise target coverage, or increase dose to organs
at risk.
PMID- 28417334
TI - Sleep quality, duration, and breast cancer aggressiveness.
AB - PURPOSE: Epidemiological studies suggest that short sleep duration and poor sleep
quality may increase breast cancer risk. However, whether sleep is associated
with breast tumor aggressiveness characteristics has largely been unexplored.
METHODS: The study included 4171 non-Hispanic whites (NHW) and 235 African
Americans (AA) diagnosed with incident, primary, invasive breast cancer in the
Women's Health Initiative (WHI) Observational Study (1994-2013). We used logistic
regression to examine the association of baseline sleep (sleep duration, sleep
quality, WHI Insomnia Rating Scale) with tumor grade, stage, hormone receptor
status, HER2 status. RESULTS: In NHW, women who reported 6 h of sleep/night were
more likely to have tumors classified as regional/distant stage at diagnosis
compared to women who slept 7-8 h/night (adjusted odds ratio (OR): 1.25, 95%
confidence interval (CI): 1.05-1.48). AA women who reported their typical night's
sleep as 'average quality' or 'restless or very restless sleep' were more likely
to be diagnosed with triple-negative tumors than those who reported 'sound or
restful' sleep (adjusted ORs: 2.91 (1.11, 7.63) and 3.74 (1.10, 12.77),
respectively). CONCLUSIONS: Our findings provide indications that aspects of
sleep (sleep duration and quality), partially modifiable health behaviors, may be
associated with development of aggressive tumor characteristics in postmenopausal
women. The role of these sleep attributes may differ for NHW and AA women;
however, further study in robust, racial diverse samples is needed. This study
provides evidence that facets of sleep behavior are associated with the
development of aggressive tumor features and these associations differ by race.
PMID- 28417335
TI - Poor prognosis of patients with triple-negative breast cancer can be stratified
by RANK and RANKL dual expression.
AB - PURPOSE: As clinical studies have correlated RANK expression levels with survival
in breast cancer, and that RANK signaling is dependent on its cognate ligand
RANKL, we hypothesized that dual protein expression further stratifies the poor
outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC
using genomic databases, cell lines and in a tissue microarray of curated primary
tumor samples derived from 87 patients with TNBC. RANK expression was evaluated
either by Mann-Whitney U test on log-normalized gene expression data or by
Student's t test on FACS data. Analysis of RANK and RANKL immunostaining was
calculated by H-score, and correlations to clinical factors performed using chi 2
or Fisher's exact test. Associations with RFS and OS were assessed using
univariate and multivariate Cox proportional hazard models. Survival estimates
were generated using the Kaplan-Meier method. RESULTS: In three distinct datasets
spanning 684 samples, RANK mRNA expression was higher in primary tumors derived
from TNBC patients than from those with other molecular subtypes (P < 0.01). Cell
surface-localized RANK protein was consistently higher in TNBC cell lines (P =
0.037). In clinical samples, TNBC patients that expressed both RANK and RANKL
proteins had significantly worse RFS (P = 0.0032) and OS (P = 0.004) than
patients with RANK-positive, RANKL-negative tumors. RANKL was an independent,
poor prognostic factor for RFS (P = 0.04) and OS (P = 0.01) in multivariate
analysis in samples that expressed both RANK and RANKL. CONCLUSIONS: RANK and
RANKL co-expression is associated with poor RFS and OS in patients with TNBC.
PMID- 28417336
TI - Treatment of Depression in Adults with Fabry Disease.
AB - Fabry disease (FD) is a genetic X-linked, multisystemic, progressive lysosomal
storage disorder (LSD). Depression has emerged as a disease complication, with
prevalence estimates ranging from 15 to 62%. This is a pilot study examining the
effects of psychological counseling for depression in FD on depression, adaptive
functioning (AF), quality of life (QOL), and subjective pain experience.
Telecounseling was also piloted, as it has beneficial effects in other chronic
diseases which make in-person counseling problematic. Subjects completed 6 months
of in-person or telecounseling with the same health psychologist, followed by 6
months without counseling. Self-report measures of depression, AF, QOL, and
subjective pain were completed every 3 months. All subjects experienced
improvements in depression, which were sustained during the follow-up period.
Improvements in depression were correlated with improvements in mental health QOL
and subjective pain severity, while improvements in mental health QOL were
correlated with improvements in AF. While statistical comparison between
counseling modes was not possible with the given sample size, relevant
observations were noted. Recommendations for future research include replication
of results with a larger sample size and a longer counseling period. The use of
video counseling may be beneficial. In conclusion, the present pilot study
supports the efficacy of psychological treatment for depression in people with
FD, highlighting the importance of having health psychologists housed in LSD
treatment centers, rather than specialty psychology/psychiatry settings, to
increase participation and decrease potential obstacles to access due to
perceived stigma.
PMID- 28417337
TI - Descemet stripping automated endothelial keratoplasty versus descemet membrane
endothelial keratoplasty: a meta-analysis.
AB - PURPOSE: To evaluate the efficacy and safety of descemet stripping automated
endothelial keratoplasty (DSAEK) compared with descemet membrane endothelial
keratoplasty (DMEK). METHODS: Databases including PubMed, EMBASE, and Cochrane
Library were searched to find studies that compared DSAEK and DMEK outcomes.
Efficacy parameters were the postoperative best-corrected visual acuity (BCVA)
and spherical equivalent (SE). Safety parameters were postoperative endothelial
cell loss (ECL), air injection (rebubbling), graft failure, graft rejection, and
high intraocular pressure (IOP). Results from last visit were pooled for the
analyses because the follow-up ranged from 3 to 24 months. RESULTS: A total of 7
trials including 433 eyes were selected for this meta-analysis. BCVA was reported
in all 7 studies, ECL% and rebubbling rate were reported in 6, and the remaining
outcomes were reported in only 3 or 2 studies. Postoperative logMAR BCVA was
significantly better for DMEK than that for DSAEK (P < 0.00001). More patients
achieved the postoperative BCVA >= 20/25 and 20/20 in DMEK group than that in
DSAEK (P > 0.001), whereas the proportion of patients whose postoperative BCVA >=
20/40 and the amount of SE did not differ statistically (P = 0.32 and P = 0.50,
respectively). The DSAEK group has a significantly lower frequency of rebubbling
than the DMEK group (P < 0.0001). The postoperative ECL%, graft failure, graft
rejection, and high IOP were comparable between the 2 groups (all P values
>0.05). CONCLUSIONS: Our meta-analysis suggests that DMEK provided better visual
outcomes with similar safety when compared to DSAEK. Given the limited sample
size, further investigations are needed to validate these findings.
PMID- 28417338
TI - Accessibility, accountability, affordability: healthcare policy in orthopedic
trauma.
AB - PURPOSE OF REVIEW: This review provides historical background on trauma care in
the USA and summarizes contemporary trauma-related health policy issues. It is a
primer for orthopedic surgeons who want to promote improvements in research,
delivery, and cost reduction in trauma care. RECENT FINDINGS: As of 2010, funding
for trauma research accounted for only 0.02% of all National Institutes of Health
research funding. This is disproportionate to the societal burden of traumatic
injury, which is the leading cause of death and disability among people aged 1 to
46 years in the USA. The diagnosis-related group model of hospital reimbursement
penalizes level-I trauma centers, which typically treat the most severely injured
patients. Treatment of traumatic injury at level-I and level-II trauma centers is
associated with lower rates of major complications and death compared with
treatment at non-trauma centers. Patient proximity to trauma centers has been
positively correlated with survival after traumatic injury. Inadequate funding
has been cited as a reason for recent closures of trauma centers. Orthopedic
surgeons have a responsibility to engage in efforts to improve the quality,
accessibility, and affordability of trauma care. This can be done by advocating
for greater funding for trauma research; choosing the most cost-effective,
patient-appropriate orthopedic implants; supporting the implementation of a
national trauma system; leading high-quality research of trauma patient outcomes;
and advocating for greater accessibility to level-I trauma centers for
underserved populations.
PMID- 28417339
TI - Expression and function of the small-conductance Ca2+-activated K+ channel is
decreased in urinary bladder smooth muscle cells from female guinea pig with
partial bladder outlet obstruction.
AB - PURPOSE: Overactive bladder (OAB), usually accompanied by partial bladder outlet
obstruction (PBOO), is associated with detrusor overactivity (DO) which is
related to the increased urinary bladder smooth muscle (UBSM) cells excitability.
Small-conductance Ca2+-activated K+ (SK) channels play a constitutive regulatory
role of UBSM excitability and contractility. PBOO is associated with the
decreased SK channels mRNA expression and the attenuated regulative effect of SK
channels on UBSM contractility. However, the regulation of SK channels in PBOO
UBSM cell excitability is less clear. Here, we tested the hypothesis that PBOO is
associated with decreased expression and function of SK channels in UBSM cells
and that SK channels are a potential target for the treatment of OAB. METHODS:
Cystometry indicated that DO was achieved 2 weeks after PBOO in female guinea
pigs. Using this animal model, we conducted single-cell quantitative reverse
transcription-polymerase chain reaction (qRT-PCR) and patch-clamp
electrophysiology. RESULTS: The single-cell qRT-PCR experiments indicated the
reduced SK channel mRNA expression in PBOO UBSM cells. Patch-clamp studies
revealed that NS309 had a diminished effect on resting membrane potential
hyperpolarization via the activation of SK channels in PBOO UBSM cells. Moreover,
attenuated whole-cell SK channel currents were demonstrated in PBOO UBSM cells.
CONCLUSIONS: The attenuated expression and function of SK channels, which results
in the increased UBSM cells excitability and contributes to DO, was discovered in
PBOO UBSM cells, suggesting that SK channels might be potential therapeutic
targets for the control of OAB.
PMID- 28417341
TI - External validation of a nomogram including the computed tomography imaging score
to predict indolent renal masses.
AB - PURPOSE: To assess a nomogram including the computed tomography (CT) score and
body mass index (BMI) that was constructed to predict indolent diseases in a
cohort of patients with renal masses. MATERIALS AND METHODS: The data collected
from patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN)
between January 2012 and September 2016 were analyzed. Two urologic surgeons and
a radiologist reviewed the images to determine the CT score. Postoperative
pathological assessment was performed to categorize renal masses as either
indolent or aggressive. The BMI and CT scores were included in the nomogram to
identify the risk of indolent disease. The performance of the novel model was
assessed by using discrimination, calibration plots, and decision curve analysis
(DCA). RESULTS: Two hundred and two participants (with 202 masses) who underwent
RN or PN were included; 37% of the masses were indolent. The predictive
performances of the nomogram revealed areas under the curve of 0.866 for masses
of all cases and 0.808 for cT1 masses without visible fat. DCA revealed that the
nomogram was moderately clinically useful. The calibration plots showed a
reasonable calibration and systematic overestimation of indolent disease based on
nomogram predictions. CONCLUSIONS: The CT score nomogram discriminated well
between indolent and aggressive renal masses. The model had a reasonable
calibration in our cohort for discriminating indolent from aggressive lesions.
Further research to validate and assess the nomogram is required.
PMID- 28417340
TI - Preconditioning of primary human renal proximal tubular epithelial cells without
tryptophan increases survival under hypoxia by inducing autophagy.
AB - PURPOSE: Hypoxia plays a significant role in the pathogenesis of acute kidney
injury (AKI). Autophagy protects from AKI. Amino acid deprivation induces
autophagy. The effect of L-tryptophan depletion on survival and autophagy in
cultures of renal proximal tubular epithelial cells (RPTECs) under hypoxia was
evaluated. METHODS: RPTECs were preconditioned in a medium containing or not
tryptophan, following culture under hypoxia and treatment with or without the
autophagy inhibitor chloroquine. Cell survival was assessed by cell imaging, the
level of certain proteins by western blotting and cellular ATP fluorometrically.
RESULTS: Preconditioning of RPTECs in a medium without tryptophan activated
general control nonderepressible 2 kinase and induced changes that favored
autophagy and cell survival under hypoxic conditions. Additionally, it increased
cellular ATP, while it inhibited apoptosis. Inhibition of autophagy nullified the
induced increase in cellular ATP and cell survival by the absence of tryptophan.
The absence of tryptophan increased p53, although its effect on p53's
transcriptional targets was heterogeneous. In accordance with the decreased
apoptosis, expression of p21 increased, while expression of Bax decreased. The
expression of BNIP3L, which may be pro-apoptotic or pro-autophagic, increased.
Considering the decreased apoptosis, it is likely that tryptophan depletion
enhances autophagy through a p53-mediated increase of BNIP3L. CONCLUSION:
Preconditioning of primary human RPTECs in a medium without tryptophan increases
their survival under hypoxia by inducing autophagy. Identifying new molecular
mechanisms that protect renal tissue from hypoxia could be proved clinically
important in the prevention of AKI.
PMID- 28417342
TI - Adipose tissue-derived stem cell therapy for erectile dysfunction in rats: a
systematic review and meta-analysis.
AB - OBJECTIVE: We aimed to systematically assess the effect of adipose tissue-derived
stem cell (ADSC) therapy and its influential factors on the treatment of erectile
dysfunction (ED) in rats. METHODS: Two authors independently searched for
published studies through PubMed and EMBASE from study inception until August 31,
2016. A meta-analysis was used to combine the effect estimate from the published
studies. A subgroup analysis was performed to identify the effect of some
influential factors. The pooled standardized mean differences (SMDs) with 95%
confidence intervals (CIs) were calculated by a fixed-effects or random-effects
model analysis. RESULTS: Twenty studies with a total of 248 rats were included in
this meta-analysis. The pooled analysis showed that ADSC therapy significantly
increased the ratio of intracavernous pressure and mean arterial pressure
(ICP/MAP; SMD 3.46, 95% CI 2.85-4.06; P < 0.001) compared to control therapy. The
levels of neuronal nitric oxide synthase (nNOS; SMD 6.37, 95% CI 4.35-8.39; P <
0.001), the cavernous smooth muscle content (CSMC; SMD 3.65, 95% CI 2.65-4.65; P
< 0.001), the ratio of cavernous smooth muscle and collagen (CSM/collagen; SMD
4.16, 95% CI 2.59-5.72; P < 0.001), and the cyclic guanosine monophosphate (cGMP;
SMD 7.12, 95% CI 2.76-11.48; P = 0.001) were higher following ADSC therapy than
following control therapy. Subgroup analysis showed that ADSCs modified by growth
or neurotrophic factors significantly recovered erectile function (P < 0.001)
compared with ADSC therapy. CONCLUSION: The adequate data indicated that ADSC
therapy recovered erectile function and regenerated cavernous structures in ED
rats, and ADSCs modified by some growth and neurotrophic factors accelerated the
recovery of erectile function and cavernous structures in ED rats.
PMID- 28417343
TI - Adjuvant Therapy for Melanoma.
AB - Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at
high risk for disease recurrence and death targets residual micrometastatic
disease which is the source of future local or distant relapse. Interferon-alfa
(IFNalpha) has been the most extensively studied in regimens that varied by
dosage, route of administration, formulation, and duration of therapy. Most
regimens have demonstrated improvements in relapse-free survival (RFS), while the
regimen administered at high dosage (HDI) showed improvements in overall survival
(OS) in two out of three RCTs. HDI benefits as measured by the hazard ratios (HR)
in E1684 (vs. observation), E1690 (vs. observation), and E1694 (vs. vaccine)
trials were estimated at 0.61, 0.78, and 0.67 (RFS) and 0.67, 1.0, and 0.72 (OS)
when first reported with lesser estimates on later updates. Pegylated IFNalpha
(peg-IFN) as studied in the European Organisation for Research and Treatment of
Cancer (EORTC) 18991 trial in patients with stage III melanoma significantly
reduced the risk of relapse (HR 0.87) with no impact on OS. More recently (EORTC
18071), ipilimumab at the high dose of 10 mg/kg was shown to significantly
improve RFS (HR 0.76) and OS (HR 0.72) of stage III melanoma patients but at a
significant cost in terms of immune-related toxicities. Ongoing adjuvant studies
are testing ipilimumab at 3 or 10 mg/kg versus HDI (E1609) and the anti-PD-1
antibodies nivolumab (CheckMate 238) and pembrolizumab (KEYNOTE-054 and S1404).
PMID- 28417344
TI - Biotherapy in Inflammatory Diseases of the CNS: Current Knowledge and
Applications.
AB - OPINION STATEMENT: Biotherapy represents an innovative therapeutic approach that
includes immunotherapy (vaccines, apheresis, and antibodies); gene therapy; and
stem cell transplants. Their development helps to cross the bridge from bench to
bedside and brings new hope of a cure for severe diseases in different fields of
medicine. In neurology, a growing range of applications is being developed for
these medications. Valuable results are now available in the field of
autoimmunity, neuro-oncology, paraneoplastic manifestations, and
neurodegenerative disorders. In this review, we examine the current and future
applications of biotherapy in the field of inflammation of the central nervous
system. We demonstrate its contribution in clinical practice, where it has
enabled a significant level of effectiveness to be achieved. Indeed, the efficacy
of these new biodrugs provides a solution for patients refractory to standard
therapies, such as intravenous immunoglobulins in limbic encephalitis, plasma
exchanges in neuromyelitis optica and anti-CD20 monoclonal antibodies in multiple
sclerosis. They also mark the first steps towards individualized medicine.
PMID- 28417345
TI - Imaging Markers for Monitoring Disease Activity in Multiple Sclerosis.
AB - OPINION STATEMENT: Multiple sclerosis (MS) is an immune-mediated disease
affecting the central nervous system (CNS). Magnetic resonance imaging (MRI) has
long been recognized as an important tool in the diagnosis of MS. It is
increasingly recognized that in addition to its role in diagnosis, MRI can play a
key role as a noninvasive tool for prognostication, disease monitoring,
assessment of treatment efficacy, and safety monitoring of disease-modifying
therapies (DMTs). A confluence of factors, including increased availability of
MRI, development of improved MRI techniques, and increased availability of DMTs
have contributed to the expanding role of MRI in MS clinical care. As the
clinical use of MRI in MS expands, it is important that MRI protocols amongst
clinical centers are standardized. Here, we summarize recent evidence supporting
the use of MRI in clinical practice, summarize various clinical guidelines and
recommendations for the use of MRI in MS disease monitoring, and provide our
recommendations for standardized MRI protocols.
PMID- 28417346
TI - [Role of primaquine in malaria control and elimination in French-speaking
Africa].
AB - Primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug
in French-speaking African countries. It acts against the liver stage parasites
of all human malaria species, asexual blood stages of Plasmodium vivax and, to a
lesser degree, Plasmodium falciparum; P. falciparum mature gametocytes, and P.
vivax and Plasmodium ovale hypnozoites. Gastrointestinal disturbances are its
most common side effects. The clinical utility of primaquine is limited due to
its hematological side effects in individuals with glucose-6-phosphate
dehydrogenase (G6PD) deficiency and other contraindications (pregnant woman,
breastfeeding woman, infants less than 6 months old). In the light of the recent
recommendations of the World Health Organization (WHO), we propose to examine how
primaquine can be used in French-speaking Africa to improve malaria control and
move towards malaria elimination. Two indications supported by the WHO are of
relevance in Africa. First, artemisinin-based combination therapies and
primaquine given as a single low dose (0.25 mg base/kg) are effective to kill
asexual and sexual parasites of P. falciparum, are well-tolerated, and have very
little risk even in mild to moderate G6PD-deficient patients. This strategy may
be helpful to contain transmission in an area in Africa where P. falciparum
malaria incidence has decreased considerably. There is an ethical concern in
administering primaquine as a gametocytocide as it does not confer any direct
benefit to the treated patient. However, the single low-dose primaquine is most
likely associated with very low risk for adverse hematological effects, and WHO
recommends its use even without prior G6PD testing. In our opinion, clinical
studies including G6PD test should be conducted to assess the safety of low-dose
primaquine in African patients. Second, primaquine is effective and necessary for
radical treatment of P. vivax and P. ovale, but the standard 14-day treatment
(0.25-0.5 mg base/kg/day) is not recommended in patients with G6PD deficiency.
Prior G6PD testing is required before prescribing primaquine for radical
treatment. The use of primaquine for radical treatment in patients without
contraindications does not raise any major ethical problem since the probability
of relapse in patients who do not receive anti-hypnozoite treatment can be
relatively high and each relapse can cause or aggravate anemia, especially in
children. In our opinion, patients with mild or moderate G6PD deficiency should
not be treated with primaquine at present. Further clinical studies are necessary
to define the role of this drug for radical treatment in G6PD-deficient African
patients. Without primaquine, the eventual elimination of P. vivax and P. ovale
malaria appears to be very difficult. Updated epidemiological data on G6PD, Duffy
antigen, and the current distribution of and burden due to P. vivax and P. ovale
are required for a rational use of primaquine in the African continent. Moreover,
clinical studies on primaquine are required in Africa.
PMID- 28417347
TI - [Serological markers of viral hepatitis B and C in children with sickle cell
disease monitored in the Pediatrics Department at the University Hospital of Bobo
Dioulasso (Burkina Faso)].
AB - Viral hepatitis B and C are universal public health problems. Burkina Faso is a
high endemic area for hepatitis B. Patients with sickle cell disease are at risk.
The aim of this study was to investigate and quantify the serological markers of
viral hepatitis B and C among pediatric patients with sickle cell disease. This
was a descriptive cross-sectional study, which took place from July to November
2014 at the Department of Pediatrics, University Hospital of Bobo- Dioulasso. The
study included 44 SS and 26 SC sickle cell patients. General data (age, gender)
and medical information (vaccinations, medical history including transfusion)
were collected. Blood samples were taken for research and titration of
serological markers of hepatitis viruses B and C with a commercial Elisa test on
the ARCHITECT i1000(r) automat of Abbott Laboratories. The mean age of the
patients was 7.98 years. Seventeen patients (13 SS and SC 4) had already been
transfused at least once. The transfusion rate was significantly higher among the
SS patients than among SC (29.5% and 15.3% respectively) patients. No patient
with HBs Ag was been found. In two patients, the anti-HBc Ab was found alone. In
33% of cases, no markers of hepatitis B were found. Less than 20% of children
fully vaccinated (N = 45) had a protective level of anti-HBs Ab (greater than 10
IU/l). The prevalence of anti-VHC Ab was 2.8%. No case of HBV-HCV co-infection
was found. The prevention of infection is an important part of the management of
sickle cell patients. Immunization against hepatitis B should be systematic. The
results of this study assume that blood safety was good.
PMID- 28417348
TI - Elevated progesterone and its impact on birth weight after fresh embryo
transfers.
AB - PURPOSE: The purpose of the study was to examine the association between serum
progesterone levels on the day of hCG administration and birth weight among
singleton live births after fresh embryo transfer. METHODS: This study was
conducted as a retrospective cohort database analysis on patients who underwent
IVF treatment cycles from January 2004 to April 2012. The study was performed at
a University affiliated private infertility practice. All cycles that had
achieved a singleton live birth after fresh embryo transfer and for which
progesterone was measured on the day of hCG administration were examined.
Generalized linear models were used to calculate mean birth weight and z-scores.
RESULTS: We analyzed 817 fresh IVF embryo transfers in which birth weight,
gestational age, and progesterone (ng/mL) level on day of hCG administration were
documented. While there was a decrease in birth weight as progesterone quartile
[<=0.54; >0.54 to <=0.81; >0.81 to <=1.17; >1.17 ng/mL] increased, the difference
in mean birth weights among the four quartiles was not statistically significant
(p = 0.11) after adjusting for maternal age and peak estradiol levels. When
dichotomizing based on a serum progesterone considered clinically elevated,
cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton
birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with
progesterone <=2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after
adjusting for maternal age and estradiol. CONCLUSION: We demonstrated that
caution should be exercised when performing fresh embryo transfers with elevated
progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead
to lower birth weight.
PMID- 28417350
TI - Does DHEA supplementation in IVF patients result in supraphysiological DHEA-S
serum concentrations?
PMID- 28417349
TI - A higher prevalence of endometriosis among Asian women does not contribute to
poorer IVF outcomes.
AB - PURPOSE: The purpose of the study was to determine whether diagnosis of
endometriosis or endometriosis with endometrioma influences in vitro
fertilization (IVF) outcomes in an ethnically diverse population. METHODS: Women
undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31,
2009, at a university-affiliated infertility clinic, were retrospectively
assessed for an endometriosis diagnosis. Differences in prevalence of
endometriosis by ethnicity were determined, as well as differences in IVF success
by ethnicity, with a focus on country of origin for Asian women. A multivariate
model was generated to assess the relative contributions of country of origin and
endometriosis to chance of clinical pregnancy with IVF. RESULTS: Endometriosis
was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of
endometrioma. Endometriosis prevalence in Asian women was significantly greater
than in Caucasians (15.7 vs. 5.8%, p < 0.01). Women of Filipino (p < 0.01),
Indian (p < 0.01), Japanese (p < 0.01), and Korean (p < 0.05) origin specifically
were more likely to have endometriosis than Caucasian women, although there was
no difference in endometrioma presence by race/ethnicity. Oocyte quantity, embryo
quality, and fertilization rates did not relate to endometriosis. Clinical
pregnancy rates were significantly lower for Asian women, specifically in Indian
(p < 0.05), Japanese (p < 0.05), and Korean (p < 0.05) women, compared to
Caucasian women, even after controlling for endometriosis status. CONCLUSIONS:
The prevalence of endometriosis appears to be higher in Filipino, Indian,
Japanese, and Korean women presenting for IVF treatment than for Caucasian women;
however, the discrepancy in IVF outcomes was conditionally independent of the
presence of endometriosis. Future research should focus on improving pregnancy
outcomes for Asian populations whether or not they are affected by endometriosis,
specifically in the form of longitudinal studies where exposures can be captured
prior to endometriosis diagnoses and infertility treatment.
PMID- 28417351
TI - Detrimental effect of maternal and post-weaning high-fat diet on the reproductive
function in the adult female offspring rat: roles of insulin-like growth factor 2
and the ovarian circadian clock.
AB - PURPOSE: We evaluate the impact of maternal and post-weaning high-fat (HF) diet
on ovarian follicular population, steroidogenesis, and gene expression with a
focus on the circadian clock system and insulin-like growth factor 2 (Igf2) in
adult offspring ovaries, and to elucidate whether a maternal and post-weaning
diet confers similar risks. METHODS: Virgin Sprague-Dawley rats were fed with
normal chow (C) diet or HF diet for 5 weeks before mating, during gestation, and
lactation. Female offspring were fed with the C or HF diet from weaning to 6
months of age, resulting in four study groups (n = 6 per group): C/C, C/HF, HF/C,
and HF/HF. RESULTS: Ovaries from offspring exposed to post-weaning HF diet (i.e.,
the C/HF and HF/HF groups) had a decrease in small follicle numbers, but with
similar numbers of antral follicles and corpora lutea. Offspring from HF-fed dams
(i.e., the HF/C and HF/HF groups) had increased plasma estradiol concentrations
and decreased luteinizing hormone levels at 6 months of age. In addition, Igf2
and each of the circadian rhythm core genes Clock, Per1, Per2, and Per3 were
increased in the ovaries of offspring exposed to maternal HF diet (both HF/C and
HF/HF groups). CONCLUSIONS: Maternal and post-weaning HF diet programs the
reproductive profile of the female offspring in adult life through different
manners. Post-weaning HF intake resulted in the reduction of small follicles in
adulthood, whereas maternal HF diet had long-term deleterious consequences on
female offspring steroidogenesis and coincided with alteration of the
upregulation of the imprinted gene Igf2 and changes in ovarian circadian rhythms.
PMID- 28417352
TI - Follicular ADAMTS-1 and aggrecan levels in polycystic ovary syndrome.
AB - PURPOSE: Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory
dysfunction and female infertility. The etiopathogenetic mechanisms of PCOS have
been studied for many years, although exact causes remain unclear. It has been
demonstrated that proteoglycan degradation by a disintegrin-like
metalloproteinase with thrombospondin type motifs-1 (ADAMTS-1) is essential for
ovulation and fertilization. The objective of our study is to analyze the levels
of ADAMTS-1 and aggrecan in the follicular fluid (FF) of PCOS patients compared
with normal ovulatory women and to determine whether these markers could be a
predictor of in vitro fertilization (IVF) success in PCOS patients. METHODS:
Women with PCOS (n = 21) and normal ovulatory controls (n = 22) undergoing IVF
treatment were recruited. ADAMTS-1 and aggrecan levels were analyzed with enzyme
linked immunosorbent assay (ELISA) and compared between PCOS and normal ovulatory
controls. The predictor effect of ADAMTS-1 and aggrecan on fertilization rate and
implantation was evaluated. RESULTS: FF ADAMTS-1 and aggrecan levels increased in
women with PCOS compared to controls. Elevated ADAMTS-1 levels but not aggrecan
were related to increased implantation in PCOS. CONCLUSION: Our study
demonstrated that altered levels of ADAMTS-1 and aggrecan may have a partial role
in the etiopathogenesis of PCOS, and ADAMTS-1 could be a predictive marker for
implantation success in PCOS patients.
PMID- 28417353
TI - The electronic medical record in anesthesiology: a standard of quality healthcare
and patient safety.
PMID- 28417354
TI - Perioperative epidural analgesia is not associated with increased survival from
renal cell cancer, but overall survival may be improved: a retrospective chart
review.
AB - PURPOSE: We investigated the possible association between perioperative epidural
and both cancer-specific survival (CSS) and overall survival (OS) in patients
undergoing partial or radical nephrectomy for localized renal cell carcinoma
(RCC). METHODS: A retrospective chart review was performed on patients who
underwent complete surgical resection of localized RCC from 1994-2008 at our
institution. Baseline demographics and pathological and survival data were
collected. Patients with clinically or pathologically positive lymph nodes or
metastatic disease at the time of surgery were excluded. Patients with
pathologically positive surgical margins were also excluded. Patients were
divided into two groups, systemic analgesia and epidural analgesia. Multivariable
Cox regression analysis was used to determine CSS and OS, and survival curves
were generated using the Kaplan-Meier method. RESULTS: Four hundred thirty-eight
patients were included in the analysis. Baseline characteristics of both groups
were similar. Median follow-up was 77 months. On multivariable analysis, patient
age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02 to 1.07),
epidural status (HR, 0.5; 95% CI, 0.4 to 0.8), year of surgery (HR, 0.9; 95% CI,
0.89 to 0.95), and pathologic T-stage (pT-stage) >= 2 (pT-stage2: HR, 2.2; 95%
CI, 1.2 to 4.1 and pT-stage3: HR, 3.1; 95% CI, 2.0 to 4.7) were independent
predictors of OS. Nevertheless, epidural status did not significantly predict CSS
(P = 0.73), while T-stage and year of surgery maintained their respective
predictive significance. Tumour grade did not significantly affect OS or CSS.
CONCLUSIONS: Our retrospective analysis suggests that epidural at the time of
surgical excision of localized RCC does not significantly impact CSS.
Nevertheless, use of epidural was associated with significantly improved OS.
Future prospective clinical and laboratory studies are warranted in order to
characterize these associations further and determine the underlying mechanisms.
PMID- 28417356
TI - A Low-Volume, Parallel Copper-Bicinchoninic Acid (BCA) Assay for Glycoside
Hydrolases.
AB - The quantitation of liberated reducing sugars by the copper-bicinchoninic acid
(BCA) assay provides a highly sensitive method for the measurement of glycoside
hydrolase (GH) activity, particularly on soluble polysaccharide substrates. Here,
we describe a straightforward method adapted to low-volume polymerase chain
reaction (PCR) tubes which enables the rapid, parallel determination of GH
kinetics in applications ranging from initial activity screening and assay
optimization, to precise Michaelis-Menten analysis.
PMID- 28417355
TI - Radiofrequency versus microwave ablation for treatment of the lung tumours:
LUMIRA (lung microwave radiofrequency) randomized trial.
AB - The LUMIRA trial evaluated the effectiveness of radiofrequency (RFA) and
microwave ablation (MWA) in lung tumours ablation and defining more precisely
their fields of application. It is a controlled prospective multi-centre random
trial with 1:1 randomization. Fifty-two patients in stage IV disease (15 females
and 37 males, mean age 69 y.o., range 40-87) were included. We randomized the
patients in two different subgroups: MWA group and RFA group. For each group, we
evaluated the technical and clinical success, the overall survival and
complication rate. Inter-group difference was compared using Chi-square test or
Fisher's exact test for categorical variables and one-way ANOVA test for
continuous variables. For RFA group, there was a significant reduction in tumour
size only between 6 and 12 months (p value = 0.0014). For MWA group, there was a
significant reduction in tumour size between 6 and 12 months (p value = 0.0003)
and between pre-therapy and 12 months (p value = 0.0215). There were not
significant differences between the two groups in terms of survival time (p value
= 0.883), while the pain level in MWA group was significantly less than in RFA
group (1.79 < 3.25, p value = 0.0043). In conclusion, our trial confirms RFA and
MWA are both excellent choices in terms of efficacy and safety in lung tumour
treatments. However, when compared to RFA therapy, MWA produced a less
intraprocedural pain and a significant reduction in tumour mass.
PMID- 28417357
TI - Quantitative Kinetic Characterization of Glycoside Hydrolases Using High
Performance Anion-Exchange Chromatography (HPAEC).
AB - High-performance anion-exchange chromatography coupled to pulsed amperometric
detection (HPAEC-PAD) is a powerful analytical technique enabling the high
resolution separation and sensitive quantification of oligosaccharides. Here, we
describe a general method for the determination of glycoside hydrolase kinetics
that harnesses the intrinsic power of HPAEC-PAD to simultaneously monitor the
release of multiple products under conditions of low substrate conversion. Thus,
the ability to track product release under initial-rate conditions with substrate
concentrations as low as 5 MUM enables the determination of Michaelis-Menten
kinetics for glycosidase activities, including hydrolysis and transglycosylation.
This technique may also be readily extended to other carbohydrate-active enzymes
(CAZymes), including polysaccharide lyases, and glycosyl transferases.
PMID- 28417358
TI - Measuring Enzyme Kinetics of Glycoside Hydrolases Using the 3,5-Dinitrosalicylic
Acid Assay.
AB - Use of the 3,5-dinitrosalicylic acid reagent allows the simple and rapid
quantification of reducing sugars. The method can be used for analysis of
biological samples or in the characterization of enzyme reactions. Presented here
is an application of the method in measuring the kinetics of a glycoside
hydrolase reaction, including the optimization of the DNSA reagent, and the
production of a standard curve of absorbance and sugar concentration.
PMID- 28417359
TI - An Improved Kinetic Assay for the Characterization of Metal-Dependent Pectate
Lyases.
AB - Pectate lyases are a subset of polysaccharide lyases (PLs) that specifically
utilize a metal dependent beta-elimination mechanism to cleave glyosidic bonds in
homogalacturonan (HG; alpha-D-1,4-galacturonic acid). Most commonly, PLs harness
calcium for catalysis; however, some PL families (e.g., PL2 and PL22) display
preferences for transitional metals. Deploying alternative metals during beta
elimination is correlated with signature coordination pocket chemistry, and is
reflective of the evolution, functional specialization, and cellular location of
PL activity. Here we describe an optimized method for the analysis of metal
dependent polysaccharide lyases (PLs). We use an endolytic PL2 from Yersinia
enterocolitica (YePL2A) as example to demonstrate how altering the catalytic
metal within the reaction can modulate PL kinetics.
PMID- 28417360
TI - Colorimetric Detection of Acetyl Xylan Esterase Activities.
AB - Colorimetric detection of reaction products is typically preferred for initial
surveys of acetyl xylan esterase (AcXE) activity. This chapter will describe
common colorimetric methods, and variations thereof, for measuring AcXE
activities on commercial, synthesized, and natural substrates. Whereas assays
using pNP-acetate, alpha-naphthyl acetate, and 4-methylumbelliferyl acetate
(4MUA) are emphasized, common methods used to measure AcXE activity towards
carbohydrate analogs (e.g., acetylated p-nitrophenyl beta-D-xylopyranosides) and
various acetylated xylans are also described. Strengths and limitations of the
colorimetric assays are highlighted.
PMID- 28417361
TI - Methods for Determining Glycosyltransferase Kinetics.
AB - Glycosyltransferases are a class of biosynthetic enzymes that transfer individual
activated monosaccharide units to specific acceptors. Colorimetric assays using
the detection of released products such as para-nitrophenol and coupled assays
for inorganic phosphate detection allow for convenient and quantifiable kinetic
characterization. These techniques may be applied to determine the enzymatic
activity of glycosyltransferases by indirectly measuring the transfer of
nucleotide-activated donor carbohydrate units to various cognate acceptor
molecules. In addition to an overview of these methods, the protocol for
quantifying the glycosyltransferase activity used for the characterization of
penicillin-binding proteins (PBPs) involving the transfer of lipid II to form
elongated murein chains during bacterial cell wall synthesis is described herein.
PMID- 28417362
TI - Analyzing Activities of Lytic Polysaccharide Monooxygenases by Liquid
Chromatography and Mass Spectrometry.
AB - Lytic polysaccharide monooxygenases perform oxidative cleavage of glycosidic
bonds in various polysaccharides. The majority of LMPOs studied so far possess
activity on either cellulose or chitin and analysis of these activities is
therefore the main focus of this review. Notably, however, the number of LPMOs
that are active on other polysaccharides is increasing. The products generated by
LPMOs from cellulose are either oxidized in the downstream end (at C1) or
upstream end (at C4), or at both ends. These modifications only result in small
structural changes, which makes both chromatographic separation and product
identification by mass spectrometry challenging. The changes in physicochemical
properties that are associated with oxidation need to be considered when choosing
analytical approaches. C1 oxidation leads to a sugar that is no longer reducing
but instead has an acidic functionality, whereas C4 oxidation leads to products
that are inherently labile at high and low pH and that exist in a keto-gemdiol
equilibrium that is strongly shifted toward the gemdiol in aqueous solutions.
Partial degradation of C4-oxidized products leads to the formation of native
products, which could explain why some authors claim to have observed glycoside
hydrolase activity for LPMOs. Notably, apparent glycoside hydrolase activity may
also be due to small amounts of contaminating glycoside hydrolases since these
normally have much higher catalytic rates than LPMOs. The low catalytic turnover
rates of LPMOs necessitate the use of sensitive product detection methods, which
limits the analytical possibilities considerably. Modern liquid chromatography
and mass spectrometry have become essential tools for evaluating LPMO activity,
and this chapter provides an overview of available methods together with a few
novel tools. The methods described constitute a suite of techniques for analyzing
oxidized carbohydrate products, which can be applied to LPMOs as well as other
carbohydrate-active redox enzymes.
PMID- 28417363
TI - Carbohydrate Depolymerization by Intricate Cellulosomal Systems.
AB - Cellulosomes are multi-enzymatic nanomachines that have been fine-tuned through
evolution to efficiently deconstruct plant biomass. Integration of cellulosomal
components occurs via highly ordered protein-protein interactions between the
various enzyme-borne dockerin modules and the multiple copies of the cohesin
modules located on the scaffoldin subunit. Recently, designer cellulosome
technology has been established to provide insights into the architectural role
of catalytic (enzymatic) and structural (scaffoldin) cellulosomal constituents
for the efficient degradation of plant cell wall polysaccharides. Owing to
advances in genomics and proteomics, highly structured cellulosome complexes have
recently been unraveled, and the information gained has inspired the development
of designer cellulosome technology to new levels of complex organization. These
higher-order designer cellulosomes have in turn fostered our capacity to enhance
the catalytic potential of artificial cellulolytic complexes. In this chapter,
methods to produce and employ such intricate cellulosomal complexes are reported.
PMID- 28417364
TI - Affinity Electrophoresis for Analysis of Catalytic Module-Carbohydrate
Interactions.
AB - Affinity electrophoresis has long been used to study the interaction between
proteins and large soluble ligands. The technique has been found to have great
utility for the examination of polysaccharide binding by proteins, particularly
carbohydrate binding modules (CBMs). In recent years, carbohydrate surface
binding sites of proteins mostly enzymes have also been investigated by this
method. Here, we describe a protocol for identifying binding interactions between
enzyme catalytic modules and a variety of carbohydrate ligands.
PMID- 28417365
TI - Quantifying CBM Carbohydrate Interactions Using Microscale Thermophoresis.
AB - MicroScale Thermophoresis (MST) is an emerging technology for studying a broad
range of biomolecular interactions with high sensitivity. The affinity constant
can be obtained for a wide range of molecules within minutes based on reactions
in microliters. Here, we describe the application of MST in quantifying two CBM
carbohydrate interactions, a CBM3a toward cellulose nanocrystals and a CBM4
against xylohexaose.
PMID- 28417366
TI - Characterization of Protein-Carbohydrate Interactions by NMR Spectroscopy.
AB - Solution-state nuclear magnetic resonance (NMR) spectroscopy can be used to
monitor protein-carbohydrate interactions. Two-dimensional 1H-15N heteronuclear
single quantum coherence (HSQC)-based techniques described in this chapter can be
used quickly and effectively to screen a set of possible carbohydrate binding
partners, to quantify the dissociation constant (K d) of any identified
interactions, and to map the carbohydrate binding site on the structure of the
protein. Here, we describe the titration of a family 32 carbohydrate binding
module from Clostridium perfringens (CpCBM32) with the monosaccharide N
acetylgalactosamine (GalNAc), in which we calculate the apparent dissociation of
the interaction, and map the GalNAc binding site onto the structure of CpCBM32.
PMID- 28417367
TI - Measuring the Biomechanical Loosening Action of Bacterial Expansins on Paper and
Plant Cell Walls.
AB - Expansins are proteins that loosen plant cell walls but lack enzymatic activity.
Here, we describe two protocols tailored to measure the biomechanical activity of
bacterial expansin. The first assay relies on weakening of filter paper by
expansin. The second assay is based on induction of creep (long-term,
irreversible extension) of plant cell wall samples.
PMID- 28417368
TI - Bioinspired Assemblies of Plant Cell Walls for Measuring Protein-Carbohydrate
Interactions by FRAP.
AB - The interactions of proteins involved in plant cell wall hydrolysis, such as
enzymes and CBMs, significantly determine their role and efficiency. In order to
go beyond the characterization of interactions with simple ligands, bioinspired
assemblies combined with the measurement of diffusion and interaction by FRAP
offer a relevant alternative for highlighting the importance of different
parameters related to the protein affinity and to the assembly.
PMID- 28417369
TI - CBMs as Probes to Explore Plant Cell Wall Heterogeneity Using
Immunocytochemistry.
AB - Immunocytochemistry is a widely used technique to localize antigen within intact
tissues. Plant cell walls are complex matrixes of highly decorated
polysaccharides and the large number of CBM families displaying specific
substrate recognition reflects this complexity. The accessibility of large
proteins, such as antibodies, to their cell wall epitopes may be sometimes
difficult due to steric hindrance problems. Due to their smaller size, CBMs are
interesting alternative probes. The aim of this chapter is to describe the use of
CBM as probes to explore complex polysaccharide topochemistry in muro and to
quantify enzymatic deconstruction.
PMID- 28417370
TI - Determining the Localization of Carbohydrate Active Enzymes Within Gram-Negative
Bacteria.
AB - Investigating the subcellular location of secreted proteins is valuable for
illuminating their biological function. Although several bioinformatics programs
currently exist to predict the destination of a trafficked protein using its
signal peptide sequence, these programs have limited accuracy and often require
experimental validation. Here, we present a systematic method to fractionate gram
negative cells and characterize the subcellular localization of secreted
carbohydrate active enzymes (CAZymes). This method involves four parallel
approaches that reveal the relative abundance of protein within the cytoplasm,
periplasm, outer membrane, and extracellular environment. Cytoplasmic and
periplasmic proteins are fractionated by lysis and osmotic shock, respectively.
Outer membrane bound proteins are determined by comparing cells before and after
exoproteolytic digestion. Extracellularly secreted proteins are collected from
the media and concentrated. These four different fractionations can then be
probed for the presence and quantity of target proteins using immunochemical
methods such as Western blots and ELISAs, or enzyme activity assays.
PMID- 28417371
TI - Analysis of Complex Carbohydrate Composition in Plant Cell Wall Using Fourier
Transformed Mid-Infrared Spectroscopy (FT-IR).
AB - Fourier transformed mid-infrared spectroscopy (FTIR) is a powerful tool for
compositional analysis of plant cell walls (Acebes et al., Front Plant Sci 5:303,
2014; Badhan et al., Biotechnol Biofuels 7:1-15, 2014; Badhan et al., BioMed Res
Int 2015: 562952, 2015; Roach et al., Plant Physiol 156:1351-1363, 2011). The
infrared spectrum generates a fingerprint of a sample with absorption peaks
corresponding to the frequency of vibrations between the bonds of the atoms
making up the material. Here, we describe a method focused on the use of FTIR in
combination with principal component analysis (PCA) to characterize the
composition of the plant cell wall. This method has been successfully used to
study complex enzyme saccharification processes like rumen digestion to identify
recalcitrant moieties in low-quality forage which resist rumen digestion (Badhan
et al., BioMed Res Int 2015: 562952, 2015), as well as to characterize cell wall
mutant lines or transgenic lines expressing exogenous hydrolases (Badhan et al.,
Biotechnol Biofuels 7:1-15, 2014; Roach et al., Plant Physiol 156:1351-1363,
2011). The FTIR method described here facilitates high-throughput identification
of the major compositional differences across a large set of samples in a low
cost and nondestructive manner.
PMID- 28417372
TI - Separation and Visualization of Glycans by Fluorophore-Assisted Carbohydrate
Electrophoresis.
AB - Fluorophore-assisted carbohydrate electrophoresis (FACE) is a method in which a
fluorophore is covalently attached to the reducing end of carbohydrates, thereby
allowing visualization following high-resolution separation by electrophoresis.
This method can be used for carbohydrate profiling and sequencing, as well as for
the determination of the specificity of carbohydrate-active enzymes. Here, we
describe and demonstrate the use of FACE to separate and visualize the glycans
released following digestion of oligosaccharides by glycoside hydrolases (GHs)
using two examples: (1) the digestion of chitobiose by the streptococcal beta
hexosaminidase GH20C, and (2) the digestion of glycogen by the GH13 member SpuA.
PMID- 28417374
TI - Probing the Complex Architecture of Multimodular Carbohydrate-Active Enzymes
Using a Combination of Small Angle X-Ray Scattering and X-Ray Crystallography.
AB - The various modules in multimodular carbohydrate-active enzymes (CAZymes) may
function in catalysis, carbohydrate binding, protein-protein interactions or as
linkers. Here, we describe how combining the biophysical techniques of Small
Angle X-ray Scattering (SAXS) and macromolecular X-ray crystallography (XRC)
provides a powerful tool for examination into questions related to overall
structural organization of ultra multimodular CAZymes.
PMID- 28417373
TI - A Rapid Procedure for the Purification of 8-Aminopyrene Trisulfonate (APTS)
Labeled Glycans for Capillary Electrophoresis (CE)-Based Enzyme Assays.
AB - Purified glycan standards are required for glycan arrays, characterizing
substrate specificities of glycan-active enzymes, and to serve as retention-time
or mobility standards for various separation techniques. This chapter describes a
method for the rapid separation, and subsequent desalting, of glycans labeled
with the highly fluorescent fluorophore 8-aminopyrene 1,3,6-trisulfonate (APTS).
By using fluorophore-assisted carbohydrate electrophoresis (FACE) on
polyacrylamide gels, which utilizes equipment readily available in most molecular
biology laboratories, many APTS-labeled glycans can be simultaneously resolved.
Excising specific gel bands containing the desired APTS-labeled glycans, followed
by glycan elution from the gel and subsequent solid-phase extraction (SPE),
yields single glycan species free of excess labeling reagents and buffer
components. This chapter describes a FACE/SPE procedure ideal for preparing
glycans for capillary electrophoresis (CE)-based enzyme assays, as well as for
the purification of rare, commercially unavailable glycans from tissue culture
samples.
PMID- 28417375
TI - Metagenomics and CAZyme Discovery.
AB - Microorganisms play a primary role in regulating biogeochemical cycles and are a
valuable source of enzymes that have biotechnological applications, such as
carbohydrate-active enzymes (CAZymes). However, the inability to culture the
majority of microorganisms that exist in natural ecosystems using common culture
dependent techniques restricts access to potentially novel cellulolytic bacteria
and beneficial enzymes. The development of molecular-based culture-independent
methods such as metagenomics enables researchers to study microbial communities
directly from environmental samples, and presents a platform from which enzymes
of interest can be sourced. We outline key methodological stages that are
required as well as describe specific protocols that are currently used for
metagenomic projects dedicated to CAZyme discovery.
PMID- 28417376
TI - Identification of Genes Involved in the Degradation of Lignocellulose Using
Comparative Transcriptomics.
AB - Lignocellulosic biomass represents an abundant, renewable resource that can be
used to produce biofuels, low-cost livestock feed, and high-value chemicals. The
potential of this resource has led to intensive research efforts to develop cost
effective methods to breakdown lignocellulose. The efficiency with which the
anaerobic fungi (phylum Neocallimastigomycota) degrade plant biomass is well
recognized and in recent years has received renewed interest. Transcriptomics has
been used to identify enzymes that are expressed by these fungi and are involved
in the degradation of a range of lignocellulose feedstocks. The transcriptome is
the entire complement of coding and noncoding RNA transcripts that are expressed
by a cell under a particular set of conditions. Monitoring changes in gene
expression can provide fundamental information about the biology of an organism.
Here we outline a general methodology that will enable researchers to conduct
comparative transcriptomic studies with the goal of identifying enzymes involved
in the degradation of the plant cell wall. The method described here includes
growth of fungal cultures, isolation and sequencing of RNA, and a basic
description of data analysis for bioinformatic identification of differentially
expressed transcripts.
PMID- 28417377
TI - Isolation and Preparation of Extracellular Proteins from Lignocellulose Degrading
Fungi for Comparative Proteomic Studies Using Mass Spectrometry.
AB - Fungi utilize a unique mechanism of nutrient acquisition involving extracellular
digestion. To understand the biology of these microbes, it is important to
identify and characterize the function of proteins that are secreted and involved
in this process. Mass spectrometry-based proteomics is a powerful tool to study
complex mixtures of proteins and understand how the proteins produced by an
organism change in response to different conditions. Many fungi are efficient
decomposers of plant cell wall, and anaerobic fungi are well recognized for their
ability to digest lignocellulose. Here, we outline a protocol for the enrichment
and isolation of proteins secreted by anaerobic fungi after growth on simple
(glucose) and complex (straw and alfalfa hay) carbon sources. We provide detailed
instruction on generating protein fragments and preparing these for proteomic
analysis using reversed phase chromatography and mass spectrometry.
PMID- 28417378
TI - ?
PMID- 28417379
TI - ?
PMID- 28417380
TI - ?
PMID- 28417381
TI - [Hypertension in elderly over 80 - benefit and harm of antihypertensive
treatment].
PMID- 28417382
TI - ?
PMID- 28417383
TI - [Scabies].
PMID- 28417384
TI - [Pediculosis capitis - an update].
PMID- 28417385
TI - ?
PMID- 28417386
TI - ?
PMID- 28417387
TI - ?
PMID- 28417388
TI - ?
PMID- 28417389
TI - ?
PMID- 28417390
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PMID- 28417392
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PMID- 28417391
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PMID- 28417393
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PMID- 28417394
TI - ?
PMID- 28417395
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PMID- 28417397
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PMID- 28417396
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PMID- 28417398
TI - ?
PMID- 28417399
TI - ?
PMID- 28417400
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PMID- 28417401
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PMID- 28417402
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PMID- 28417403
TI - ?
PMID- 28417404
TI - ?
PMID- 28417405
TI - ?
PMID- 28417406
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PMID- 28417407
TI - ?
PMID- 28417408
TI - ?
PMID- 28417409
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PMID- 28417410
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PMID- 28417411
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PMID- 28417412
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PMID- 28417413
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PMID- 28417414
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PMID- 28417416
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PMID- 28417417
TI - ?
PMID- 28417419
TI - ?
PMID- 28417418
TI - ?
PMID- 28417420
TI - [Current treatment of dyspepsia in primary care].
PMID- 28417422
TI - Selection of an Artificial Diet for Laboratory Rearing of Opogona sacchari
(Lepidoptera: Tineidae) (Bojer, 1856).
AB - The banana moth Opogona sacchari (Bojer) (Lepidoptera: Tineidae) is a polyphagous
pest that can cause serious damage, in particular to banana crops in southern
Brazil. The insect is a quarantine pest in several countries, including
Argentina, the main consumer market for bananas from southern Brazil. Little
information is available about the biology and ecology of this moth, such as a
suitable diet for laboratory rearing. In order to provide support for integrated
pest management of the pest, this study furnished data for selecting two diets
suitable for continuous laboratory rearing of O. sacchari, one based on dried
beans, wheat germ, soy bran, brewer's yeast, and casein and another diet with
wheat germ and casein as protein sources. With both diets, the viability of the
egg-adult period exceeded 68%, with fertility over 338 eggs per female. A
corrected biotic potential analysis gave similar values for the two diets.
PMID- 28417421
TI - A review of infectious complications after haploidentical hematopoietic stem cell
transplantations.
AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation from
haploidentical donor is a feasible option for patients with hematological
diseases who lack a suitable HLA-matched donor, but viral and fungal infections
are still the most common causes of morbidity and mortality in haploidentical
transplantation setting because of delayed immune reconstitution, increased risk
of graft vs host disease (GvHD) or systemic steroid use. Therefore, this review
will focus on the infectious complications after haploidentical hematopoietic
stem cell transplantation (HSCT). MATERIALS AND METHODS: Electronic publications
were searched until February 2017 throughout databases, including Pubmed,
Cochrane, and Embase. The following keywords were used 'haploidentical
transplantation', 'infection', 'T cell replete', and 'T cell deplete'. RESULTS:
An increased incidence of bacterial, fungal, or viral infections is detected in
haplo-HSCT compared to related, unrelated, or cord blood transplantations.
Neutropenia and use of systemic steroid for GvHD and delayed immune
reconstitution are important risk factors for infection after haplo-HSCT.
CONCLUSION: A shift towards T cell repletes haplo-HSCT with post-transplant
cyclophosphamide (CY) for GvHD has been emerged in recent years, in which the
incidence of viral and fungal infections is detected to be lower. Prophylaxis and
pre-emptive treatment strategies should be applied according to patient status.
PMID- 28417423
TI - Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of
Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected
with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the
Study of Alzheimer's Disease Pathology.
AB - Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models
in neurodegenerative research, and their use has advanced the understanding of
the pathology of neurodegeneration over the past few decades. In Alzheimer's
disease (AD), several pathogenic mutations have been described, all of which
cause elevated levels of pathological hallmarks such as amyloid-beta (Abeta).
Although the genetics of Alzheimer's disease is well known, familial AD only
accounts for a small number of cases in the population, with the rest being
sporadic AD, which contains no known mutations. Currently, most of the in vitro
models used to study AD pathogenesis only examine the level of Abeta42 as a
confirmation of successful model generation and only perform comparisons between
wild-type APP and single mutants of the APP gene. Recent findings have shown that
the Abeta42/40 ratio in cerebrospinal fluid (CSF) is a better diagnostic
indicator for AD patients than is Abeta42 alone and that more extensive Abeta
formation, such as accumulation of intraneuronal Abeta, Abeta plaques, soluble
oligomeric Abeta (oAbeta), and insoluble fibrillar Abeta (fAbeta) occurs in
TgCRND8 mice expressing a double-mutant form (Swedish and Indiana) of APP, later
leading to greater progressive impairment of the brain. In this study, we
generated SH-SY5Y cells stably transfected separately with wild-type APP, the
Swedish mutation of APP, and the Swedish and Indiana mutations of APP and
evaluated the APP expression as well as the Abeta42/40 ratio in those cells. The
double-mutant form of APP (Swedish/Indiana) expressed markedly high levels of APP
protein and showed a high Abeta2/40 ratio compared to wild-type and single-mutant
cells.
PMID- 28417424
TI - A Review of the Anaerobic Digestion of Fruit and Vegetable Waste.
AB - Fruit and vegetable waste is an ever-growing global question. Anaerobic digestion
techniques have been developed that facilitate turning such waste into possible
sources for energy and fertilizer, simultaneously helping to reduce environmental
pollution. However, various problems are encountered in applying these
techniques. The purpose of this study is to review local and overseas studies,
which focus on the use of anaerobic digestion to dispose fruit and vegetable
wastes, discuss the acidification problems and solutions in applying anaerobic
digestion for fruit and vegetable wastes and investigate the reactor design
(comparing single phase with two phase) and the thermal pre-treatment for
processing raw wastes. Furthermore, it analyses the dominant microorganisms
involved at different stages of digestion and suggests a focus for future
studies.
PMID- 28417425
TI - Overexpression of OsHSP18.0-CI Enhances Resistance to Bacterial Leaf Streak in
Rice.
AB - BACKGROUND: The small heat shock proteins represent a large family of proteins
that respond to a wide range of abiotic and biotic stresses. OsHsp18.0-CI confers
tolerance to salt and cadmium and interacts with viral RNA-dependent RNA
polymerase (RdRp). However, the direct function of OsHsp18.0-CI in resistance
against biotic stresses remains unclear in rice. RESULTS: Here, we report that
the expression of OsHsp18.0-CI was up-regulated upon inoculation with RS105, a
strain of Xanthomonas oryzae pv. oryzicola (Xoc) that causes bacterial leaf
streak in rice. In comparison with wild-type, OsHsp18.0-CI overexpression (OE)
lines exhibited enhanced resistance to RS105, whereas repression lines exhibited
compromised resistance to RS105. In addition, the transcriptional profiles of
wild type and OE lines were compared with and without inoculation with RS105.
After inoculation with RS105, most of the genes with up-regulated expression were
commonly stimulated in the wild type and OE lines, with stronger induction in the
OE lines than in wild type. CONCLUSION: Our study reveals that OsHsp18.0-CI
positively regulates resistance to Xoc by mediating an enhanced version of the
basal defense response in rice.
PMID- 28417426
TI - Telehealth delivery of the diabetes prevention program to rural communities.
AB - The Centers for Disease Control and Prevention, State and Local Health
Departments, and other organizations in the USA are working to increase
population access to the Diabetes Prevention Program (DPP) lifestyle
intervention. Delivering the DPP through telehealth videoconference may increase
access to this intervention, particularly in rural communities. The purpose of
this study was to compare participation, monitoring of diet and physical
activity, and weight loss in participants receiving the intervention on-site and
those participating virtually through telehealth. Beginning in 2008, Holy Rosary
Healthcare collaborated with the Montana Department of Public Health and Human
Services to provide the DPP to participants on-site in one community and
simultaneously through telehealth to participants in multiple other communities.
From 2008 through 2015, 894 participants were enrolled in the program (29% at
telehealth sites). The mean age of participants was 51.7 years and 84% were
female. Overall, participants attended 14.4, 3.9, and 15.0 weekly core, post
core, and total sessions, respectively. There were no statistically significant
differences in number of intervention sessions attended by the telehealth or on
site participants. There were no statistically significant differences in the
mean weight loss or reduction in BMI between the telehealth and the on-site
groups. There also were no statistically significant differences in the
percentage of telehealth or on-site participants who achieved >=5% weight loss
(56 vs. 57%) or the 7% weight loss goal (38 vs. 41%). Our findings suggest that
participants receiving the DPP through telehealth have similar rates of
participation and achieve similar weight loss as participants attending the
program on-site.
PMID- 28417427
TI - Extraperitoneal Robot-Assisted Radical Prostatectomy: Indications, Technique and
Outcomes.
AB - PURPOSE OF REVIEW: Extraperitoneal robot-assisted radical prostatectomy (eRARP)
is an alternative to the more commonly employed transperitoneal RARP (tRARP) for
treatment of clinically localized prostate cancer. The purpose of this review is
to discuss indications in which eRARP would be a more favorable approach in
comparison to tRARP. In addition, we will discuss the safety and technique of
eRARP. RECENT FINDINGS: Recently published work has highlighted the outcomes and
safety of eRARP in comparison to tRARP; specifically that eRARP is not inferior
to tRARP. In addition, eRARP may be preferred in certain circumstances. For
example, Ludwig et al. recently discussed the concomitant repair of inguinal
hernia during eRARP. Extraperitoneal RARP is a safe and effective alternative to
tRARP. With previous knowledge and experience with tRARP, urologists can adapt
the extraperitoneal approach without difficulty. This approach is useful for
specific situations in which tRARP may be challenging.
PMID- 28417428
TI - Outcomes of Minimally Invasive Inguinal Hernia Repair at the Time of Robotic
Radical Prostatectomy.
AB - Abdominal straining associated with voiding dysfunction or constipation has
traditionally been associated with the development of abdominal wall hernias.
Thus, classic general surgery dictum recommends that any coexistent bladder
outlet obstruction should be addressed by the urologist before patients undergo
surgical repair of a hernia. While organ-confined prostate cancer is usually not
associated with the development of lower urinary tract symptoms, a modest
proportion of patients treated with radical prostatectomy may have coexisting
benign prostatic hyperplasia with elevated symptom scores and hernias may be
incidentally detected at the time of surgery. Furthermore, dissection of the
space of Retzius during retropubic or minimally invasive prostatectomy may result
exposure of abdominal wall defects which may have been present, but asymptomatic
if plugged with preperitoneal fat. Herein we examine the literature regarding the
incidence of postoperative inguinal hernias after prostatectomy, review potential
risk factors which could aid in preoperative patient identification, and discuss
the published experience regarding concurrent hernia repair at the time of open
or minimally invasive radical prostatectomy.
PMID- 28417429
TI - Approach to Androgen Deprivation in the Prostate Cancer Patient with Pre-existing
Cardiovascular Disease.
AB - PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) is a mainstay of treatment
for advanced prostate cancer. Several studies have reported an association
between ADT and an increase in cardiovascular events, especially in those
receiving gonadotropin-releasing hormone (GnRH) agonists compared to GnRH
antagonists. We review the body of literature reporting the association of ADT
and cardiovascular morbidity, and discuss the proposed mechanism of
cardiovascular disease due to ADT including metabolic changes that may promote
atherosclerosis and local hormonal effects that may increase plaque rupture and
thrombosis. RECENT FINDINGS: GnRH agonists appear to increase the risk of
cardiovascular morbidity by 20-25% in men on these agents compared those who do
not receive ADT. GnRH antagonists may appear to have halve this risk while
improving PSA progression-free survival. GnRH antagonists may be superior to GnRH
agonists for patients with significant cardiovascular disease, significant
metastatic disease burden, or severe lower urinary tract symptoms.
PMID- 28417430
TI - The Emergence of Kidney Stone Disease During Childhood-Impact on Adults.
AB - PURPOSE OF REVIEW: The goal of this chapter is to review the recent epidemiologic
trends of kidney stone disease and discuss the impact of the increasing incidence
of nephrolithiasis among children on adults with respect to extra-renal
manifestations, surgical management, and secondary prevention. RECENT FINDINGS:
Among pediatric patients, kidney stone disease has been increasing at a rate of
approximately 5-10% annually. Kidney stone disease has been associated with
increased risks of coronary heart disease, chronic kidney disease, hypertension,
and decreased bone mineral density, which is concerning for patients diagnosed at
a young age. Improvements in endo-urology have allowed for less invasive surgical
treatment of stones in the pediatric population. However, current guidelines
often lack recommendations for evaluation, medical, and surgical management of
children with kidney stone disease. Nephrolithiasis is a disorder of mineral
metabolism, which is beginning during childhood with increasing frequency. Kidney
stone disease often exists over the lifetime and is associated with serious
conditions that are important for pediatric and adult urologists to recognize and
consider in their evaluation and treatment of patients.
PMID- 28417431
TI - Robotic Kidney Transplantation-an Update.
AB - PURPOSE OF REVIEW: Over the last decade, there have been advances in kidney
transplantation with introduction of minimally invasive surgery. Robotic surgery
is becoming increasingly common across the specialities. There is now increasing
experience in robotic kidney transplantation, though it remains a niche
procedure. Initial reports suggest that this is a safe, feasible operation when
performed by teams familiar with robotic surgery. There have been a few
modifications to the initially described procedure, as a result of increasing
experience. RECENT FINDINGS: There is no significant difference in graft and
patient survival when compared with open surgery and laparoscopic kidney
transplantation. It is a safe procedure and therefore represents a viable
alternative to open surgery in selected patients particularly the obese. The
advantages include less postoperative pain and fewer wound complications such as
surgical site infections and hernia, which could be particularly advantageous in
the obese. Robotic kidney transplantation is procedure that has been developed
over the last decade and could have applicability in kidney transplantation in
the obese. Its main benefit is in enabling surgery in less accessible spaces due
to body habitus, combined with those of using a smaller incision with less
associated morbidity, with no inferiority in the reported primary outcomes of
graft and patient survival. There are capital costs associated with this
procedure, but further studies on the cost-effectiveness of robotic kidney
transplantation are needed before it can be adopted widely.
PMID- 28417432
TI - Evaluating Community Measures of Healthy Food Access.
AB - Several community level measures of healthy food access exist, but evaluation
efforts have been limited leaving uncertainty about how to prioritize communities
for intervention. This study aimed to assess several existing measures to inform
statewide public health planning efforts in New Jersey, USA. We assessed
agreement between community measures of healthy food access and then evaluated
the predictive validity of each measure by describing its association with
complete fruit and vegetable cash-value voucher redemption (proportion redeemed
>=70, >=80, >=90%) among 30,078 low-income households participating in the New
Jersey Special Supplemental Nutrition Program for Women, Infants, and Children
(WIC) during 2013-2014. The United States Department of Agriculture's (USDA) food
desert measure agreed with the Centers for Disease Control and Prevention's (CDC)
no healthier food retailers (NHFR) measure for 76.5% of New Jersey census tracts,
but the Kappa statistic was only 0.10. For urban households, the NHFR measure was
negatively associated with complete redemption after adjusting for demographic
factors and Supplemental Nutrition Assistance Program participation (>=70% odds
ratio (OR) 0.68, 95% confidence interval (CI) 0.61-0.75; >=80% OR 0.67, 95% CI
0.62-0.73; >=90% OR 0.72, 95% CI 0.66-0.77). For rural households, a negative
association was observed for the USDA's low-income/low-vehicle access measure
(>=70% OR 0.48, 95% CI 0.26-0.90). The CDC's NHFR measure is more appropriate for
prioritizing urban areas while the USDA's low-income/low-vehicle access measure
may be better for rural areas.
PMID- 28417433
TI - Investigating Responses to Food Insecurity Among HIV Positive People in Resource
Rich Settings: A Systematic Review.
AB - Many of the 36.7 million people living with HIV are also assumed to be food
insecure. The implications of food insecurity in people living with HIV are
significant, with food insecurity associated with an increased likelihood of
tobacco, alcohol, and illicit drug use, experiences of depression or depressive
symptoms, poor adherence and delayed uptake of HIV medication, nutritional
vulnerability leading to interference of medication, and the uptake of risky
behaviours as a way to gain access to food resources. This review sought to
present the current intervention research around the experiences of food
insecurity in PLWHA in high resource countries to determine successful models to
address the issue. Only five articles were identified in a systematic search,
three reported on studies that were conducted in the USA and two in Canada. Two
articles were cross sectional, one was a program evaluation, one ethnography, and
one took a qualitative approach. This review highlights a lack of published
research in the area of HIV and food insecurity in resource rich countries. The
findings of this study suggest that there are currently no standard or best
practice ways to provide food aid to PLWHA to reduce food security. The lack of
published results means that while there may be good programs operating in the
community, this information and knowledge is not being shared, resulting in a
lack of consistency in approach, possible duplication, and the potential for
wasted resources. Overall, this review suggests a need for more dedicated
evaluation and longitudinal research.
PMID- 28417434
TI - Characterizing Rural Food Access in Remote Areas.
AB - Residents of rural areas may have limited access to healthy foods, leading to
higher incidence of diet related health issues. Smaller grocers in rural areas
experience challenges in maintaining fresh produce and other healthy foods
available for customers. This study assessed the rural food environment in
northeast Lower Michigan in order to inform healthy food financing projects such
as the Michigan Good Food Fund. The area's retail food businesses were
categorized using secondary licensing, business, and nutrition program databases.
Twenty of these stores were visited in person to verify the validity of the
categories created, and to assess the availability of healthy foods in their
aisles. In-depth interviews with key informants were carried out with store
owners, economic development personnel, and other food system stakeholders having
knowledge about food access, in order to learn more about the specific challenges
that the area faces. Out-shopping, seasonality, and economic challenges were
found to affect healthy food availability. Mid-sized independent stores were
generally found to have a larger selection of healthy foods, but smaller rural
groceries also have potential to provide fresh produce and increase food access.
Potential healthy food financing projects are described and areas in need of
further research are identified.
PMID- 28417435
TI - Lachnospiraceae shift in the microbial community of mice faecal sample effects on
water immersion restraint stress.
AB - Stress, including both psychological and physical stimulation, can cause changes
in the microbiota and mucosal function of the gastrointestinal system. There are
few research studies available about the faecal microbiota changes after stress,
such as water immersion restraint stress (WIRS). Therefore, in this study, we
focused on analysing the composition changes of faecal microbiota in WIRS mice.
The WIRS model, in which Blab/c mice were immersed in 21 +/- 2 degrees C water
for 4 h each day for 14 days, was established. Behavioural changes, the serum
levels of corticosterone, IFN-gamma and IL-17 and gastric mucosal injury were
also assessed. Ten faecal microbiota samples were detected by Illumina Miseq
sequencing of the 16S rRNA genes from 367205 characterised sequences. Finally, we
find significant differences in the faecal microbiota composition between the
control and the WIRS groups. There was an obvious increase in Lachnospiraceae in
the WIRS mice (p = 0.0286, p < 0.05), which is associated with human diseases,
such as ulcerative colitis, Crohn's and celiac disease. Our research indicates
that stress changes in the faecal microbiota. These results suggest that
observing shifts of the intestinal microbiota is a promising method to explore
the mechanism of the stress associated with gastrointestinal diseases and to
provide us with a better understanding of the relationship between the microbiota
and disease.
PMID- 28417436
TI - Evaluation of the Pharmacokinetics and Pharmacodynamics of Prasugrel in Japanese
Elderly Subjects.
AB - BACKGROUND AND OBJECTIVE: An increased incidence in bleeding events has been
reported in Western elderly patients receiving prasugrel. Therefore, doses in
Japanese elderly subjects need to be carefully determined. We assessed the
pharmacokinetic and pharmacodynamic effects of prasugrel at the clinical dose
used in Japan in healthy Japanese elderly subjects compared with non-elderly
subjects. METHODS: In an open-label parallel-group study conducted in Japan, two
groups (elderly, aged >75 years; non-elderly, aged 45-65 years) received a 20-mg
loading dose and a 3.75-mg maintenance dose of prasugrel for 7 days. Plasma
concentration of its active metabolite, R-138727, and pharmacokinetic parameters
were determined on days 1 and 7 after dosing. Pharmacodynamic response to 20 uM
of adenosine diphosphate-induced platelet aggregation was measured by light
transmission aggregometry. RESULTS: A total of 47 subjects were enrolled (23
elderly, 24 non-elderly). There was no statistically significant difference in
pharmacokinetic parameters between groups: area under the plasma concentration
time curve up to the last quantifiable time and maximum plasma concentration were
about 174-175 ng.h/mL and 134-153 ng/mL, respectively, after the loading dose;
and about 25-26 ng.h/mL and 25 ng/mL, respectively, after the maintenance dose.
Inhibition of platelet aggregation was higher in the elderly subjects than in the
non-elderly subjects, with a statistically significant difference from 24 h after
the loading dose. No serious adverse events (bleeding or non-bleeding) occurred.
CONCLUSIONS: Prasugrel (20-mg loading dose; 3.75-mg maintenance dose) produced a
slight increase in antiplatelet efficacy in elderly compared with non-elderly
subjects, despite no statistically significant difference in the
pharmacokinetics.
PMID- 28417437
TI - Cumulative Impact of Stressful Life Events on the Development of Takotsubo
Cardiomyopathy.
AB - BACKGROUND: The role of stressful life events in the onset of Takotsubo
cardiomyopathy (TC) is unclear. PURPOSE: This study sought to examine
associations between type, timing, and number of stressful life events and onset
of TC. METHODS: A case-control study conducted among consecutive incident female
TC cases and myocardial infarction (MI) controls admitted to two emergency
departments in New England. Healthy female controls (HC) were recruited from a
volunteers' registry. Information about the timing, type, and number of triggers
during the 6 months preceding hospitalization was systematically collected using
the PERI Life Events Scale about 1 month post-discharge. Group differences were
evaluated using ANOVA, chi-square, and Kruskal-Wallis statistics. Generalized
linear models were used to adjust for confounding variables. RESULTS: Between
March 2013 and October 2015, 107 women were enrolled (45 TC, 32 MI, and 30 HC).
Specific stressful events (death of a relative or close friend (p = 0.006);
illness or injury to a relative or close friend (p = 0.001) were more prevalent
in TC cases than MI and HC controls. The onset of TC was associated with exposure
to multiple stressful life events during the 6 months preceding the index
hospitalization (p < 0.001) but not with exposure to an acute, recent event (p =
0.96). CONCLUSIONS: TC onset was associated with specific life events (death or
illness to close relative or friend) and with the number of stressful life events
occurring in the 6 months preceding hospitalization. These findings suggest that
grief and cumulative stress could play a major role in the onset of TC.
PMID- 28417438
TI - Examining the Support Peer Supporters Provide Using Structural Equation Modeling:
Nondirective and Directive Support in Diabetes Management.
AB - BACKGROUND: Little research has examined the characteristics of peer support.
Pertinent to such examination may be characteristics such as the distinction
between nondirective support (accepting recipients' feelings and cooperative with
their plans) and directive (prescribing "correct" choices and feelings). PURPOSE:
In a peer support program for individuals with diabetes, this study examined (a)
whether the distinction between nondirective and directive support was reflected
in participants' ratings of support provided by peer supporters and (b) how
nondirective and directive support were related to depressive symptoms, diabetes
distress, and Hemoglobin A1c (HbA1c). METHODS: Three hundred fourteen
participants with type 2 diabetes provided data on depressive symptoms, diabetes
distress, and HbA1c before and after a diabetes management intervention delivered
by peer supporters. At post-intervention, participants reported how the support
provided by peer supporters was nondirective or directive. Confirmatory factor
analysis (CFA), correlation analyses, and structural equation modeling examined
the relationships among reports of nondirective and directive support, depressive
symptoms, diabetes distress, and measured HbA1c. RESULTS: CFA confirmed the
factor structure distinguishing between nondirective and directive support in
participants' reports of support delivered by peer supporters. Controlling for
demographic factors, baseline clinical values, and site, structural equation
models indicated that at post-intervention, participants' reports of nondirective
support were significantly associated with lower, while reports of directive
support were significantly associated with greater depressive symptoms,
altogether (with control variables) accounting for 51% of the variance in
depressive symptoms. CONCLUSIONS: Peer supporters' nondirective support was
associated with lower, but directive support was associated with greater
depressive symptoms.
PMID- 28417439
TI - Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin
Receptor-Neprilysin Inhibitor.
AB - Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure
with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion
of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with
maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan
(angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h,
respectively. With a two-fold increase in dose, an increase in the area under the
plasma concentration-time curve was proportional for sacubitril, ~1.9-fold for
sacubitrilat, and ~1.7-fold for valsartan in healthy subjects. Following multiple
twice-daily administration, steady-state maximum plasma concentration was reached
within 3 days, showing no accumulation for sacubitril and valsartan, while ~1.6
fold accumulation for sacubitrilat. Sacubitril is eliminated predominantly as
sacubitrilat through the kidney; valsartan is eliminated mainly by biliary route.
Drug-drug interactions of sacubitril/valsartan were evaluated with medications
commonly used in patients with heart failure including furosemide, warfarin,
digoxin, carvedilol, levonorgestrel/ethinyl estradiol combination, amlodipine,
omeprazole, hydrochlorothiazide, intravenous nitrates, metformin, statins, and
sildenafil. Co-administration with sacubitril/valsartan increased the maximum
plasma concentration (~2.0-fold) and area under the plasma concentration-time
curve (1.3-fold) of atorvastatin; however, it did not affect the pharmacokinetics
of simvastatin. Age, sex, or ethnicity did not affect the pharmacokinetics of
sacubitril/valsartan. In patients with heart failure vs. healthy subjects, area
under the plasma concentration-time curves of sacubitril, sacubitrilat, and
valsartan were higher by approximately 1.6-, 2.1-, and 2.3-fold, respectively.
Renal impairment had no significant impact on sacubitril and valsartan area under
the plasma concentration-time curves, while the area under the plasma
concentration-time curve of sacubitrilat correlated with degree of renal function
(1.3-, 2.3-, 2.9-, and 3.3-fold with mild, moderate, and severe renal impairment,
and end-stage renal disease, respectively). Moderate hepatic impairment increased
the area under the plasma concentration-time curves of valsartan and sacubitrilat
~2.1-fold.
PMID- 28417441
TI - Relationships Between Essential Manganese Biology and Manganese Toxicity in
Neurological Disease.
AB - PURPOSE OF REVIEW: Manganese (Mn) is critical for neurodevelopment but also has
been implicated in the pathophysiology of several neurological diseases. We
discuss how Mn requirements intersect with Mn biology and toxicity, and how these
requirements may be altered in neurological disease. Furthermore, we discuss the
emerging evidence that the level of Mn associated with optimal overall efficiency
for Mn biology does not necessarily coincide with optimal cognitive outcomes.
RECENT FINDINGS: Studies have linked Mn exposures with urea cycle metabolism and
autophagy, with evidence that exposures typically neurotoxic may be able to
correct deficiencies in these processes at least short term. The line between Mn
dependent biology and toxicity is thus blurred. Further, new work suggests that
Mn exposures correlating to optimal cognitive scores in children are associated
with cognitive decline in adults. This review explores relationships between Mn
dependent neurobiology and Mn-dependent neurotoxicity. We propose the hypothesis
that Mn levels/exposures that are toxic to some biological processes are
beneficial for other biological processes and influenced by developmental stage
and disease state.
PMID- 28417440
TI - Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism.
AB - PURPOSE OF REVIEW: Epidemiological and animal studies suggest that air pollution
may negatively affect the central nervous system (CNS) and contribute to CNS
diseases. Traffic-related air pollution is a major contributor to global air
pollution, and diesel exhaust (DE) is its most important component. RECENT
FINDINGS: Several studies suggest that young individuals may be particularly
susceptible to air pollution-induced neurotoxicity and that perinatal exposure
may cause or contribute to developmental disabilities and behavioral
abnormalities. In particular, a number of recent studies have found associations
between exposures to traffic-related air pollution and autism spectrum disorders
(ASD), which are characterized by impairment in socialization and in
communication and by the presence of repetitive and unusual behaviors. The
cause(s) of ASD are unknown, and while it may have a hereditary component,
environmental factors are increasingly suspected as playing a pivotal role in its
etiology, particularly in genetically susceptible individuals. Autistic children
present higher levels of neuroinflammation and systemic inflammation, which are
also hallmarks of exposure to traffic-related air pollution. Gene-environment
interactions may play a relevant role in determining individual susceptibility to
air pollution developmental neurotoxicity. Given the worldwide presence of
elevated air pollution, studies on its effects and mechanisms on the developing
brain, genetic susceptibility, role in neurodevelopmental disorders, and possible
therapeutic interventions are certainly warranted.
PMID- 28417443
TI - Time Trends of High Blood Pressure Prevalence, Awareness and Control in the
Italian General Population : Surveys of the National Institute of Health.
AB - INTRODUCTION: High blood pressure (BP) is a major risk factor for cardiovascular
disease. The urgency of the problem was underlined by the World Health
Organization (WHO) Global Action Plan for the prevention and control of
noncommunicable diseases, which recommends a 25% relative reduction in the
prevalence of raised BP by 2020. A surveillance system represents a useful tool
to monitor BP in the general population. Since 1980s, the National Institute of
Health has conducted several surveys of the adult general population, measuring
cardiovascular risk factors by standardized procedures and methods. AIM: To
describe mean BP levels and high BP prevalence from 1978 to 2012 by sex and
quinquennia of age. METHODS: Data were derived from the following three studies:
(i) Risk Factors and Life Expectancy (RIFLE), conducted between 1978 and 2002 in
13 Italian regions (>70,000 persons); (ii) Osservatorio Epidemiologico
Cardiovascolare (OEC), conducted between 1998-2002 in the general population from
all Italian regions (>9000 persons); and (iii) Osservatorio Epidemiologico
Cardiovascolare/Health Examination Survey (OEC/HES), conducted between 2008-2012
in the general population from all Italian regions (>9000 persons). RESULTS: A
significant decrease in mean systolic and diastolic BP levels and prevalence of
high BP from 1978 to 2012 was observed both in men and women. BP and high BP
increased by age classes in all considered periods. BP awareness and control also
improved. CONCLUSION: Our data suggest that BP control could be achieved by 2020,
as recommended by WHO.
PMID- 28417442
TI - Mechanisms of Gene-Environment Interactions in Parkinson's Disease.
AB - PURPOSE OF REVIEW: The purpose of the study was to discuss the main mechanisms
associated with environmental and genetic factors that contribute to the
development of Parkinson's disease (PD). RECENT FINDINGS: Novel genetic
contributors to PD are being identified at a rapid pace in addition to novel
environmental factors. The discovery of mutations in alpha-synuclein and leucine
rich repeat kinase 2 causing inherited forms of PD along with epidemiological, in
vitro, and in vivo studies identifying herbicides, pesticides, and metals as risk
factors have dramatically improved our understanding of mechanisms involved in
the development of PD. However, at the same time, these discoveries have also
added layers of complexity to the disease. Within the last several years, the
genetics associated with PD has dominated the field in many ways; however, the
majority of PD cases are likely due to different combinations of environmental
exposures and genetic susceptibility. The most common toxicants used to model PD
including rotenone, paraquat, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
have been shown to interact with many of the genes linked with PD such as alpha
synuclein. Therefore, an understanding of mechanisms common between genetic and
environmental factors is essential for early detection and successful translation
of potential therapies, which is the ultimate goal.
PMID- 28417444
TI - A retinaculum-sparing surgical approach preserves porcine stifle joint cartilage
in an experimental animal model of cartilage repair.
AB - BACKGROUND: This study compares a traditional parapatellar retinaculum
sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle
joint as a cartilage repair model. FINDINGS: Surgical exposure of the femoral
trochlea of ten Yucatan pigs stifle joint was performed using either a
traditional medial parapatellar approach with retinaculum incision and luxation
of the patella (n = 5) or a minimally invasive (MIS) approach which spared the
patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate
access to the trochlea, enabling the creation of cartilage defects without
difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects
were created in each trochlea. There were no intraoperative complications
observed in either surgical approach. All pigs were allowed full weight-bearing
and full range of motion immediately postoperatively and were euthanized between
2 and 3 weeks. The traditional approach was associated with increased cartilage
wear compared to the MIS approach. Two blinded raters performed gross evaluation
of the trochlea cartilage surrounding the defects according to the modified ICRS
cartilage injury classification. The traditional approach cartilage received a
significantly worse score than the MIS approach group from both scorers (3.2 vs
0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). CONCLUSION: The MIS approach
results in less damage to the trochlear cartilage and faster return to load
bearing activities. As an arthrotomy approach in the porcine model, MIS is
superior to the traditional approach.
PMID- 28417446
TI - Missing atrioventricular echogenic mass during paediatric HeartWare(r)
implantation.
PMID- 28417445
TI - Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic
mouse model of HER-2-positive breast cancer.
AB - Curcumin has shown promising inhibitory activity against HER-2-positive tumor
cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has
previously developed a polymeric microparticle formulation for sustained delivery
of curcumin for chemoprevention. The goal of this study was to examine the
anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic
mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and
mice were examined for tumor appearance and growth. Initiating curcumin
microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3
weeks compared to that in control mice that received empty microparticles. At 12
weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma)
mammary tissue area was significantly decreased in curcumin microparticle-treated
mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels
significantly, which likely contributed to slower tumor formation. When compared
to saline controls, however, blank microparticles accelerated tumorigenesis and
curcumin treatment abrogated this effect, suggesting that PLGA microparticles
enhance tumorigenesis in this model. PLGA microparticle administration was shown
to be associated with higher plasma lactic acid levels and increased activation
of NF-kappaBeta. The unexpected side effects of PLGA microparticles may be
related to the high dose of the microparticles that was needed to achieve
sustained curcumin levels in vivo. Approaches that can decrease the overall dose
of curcumin (for example, by increasing its potency or reducing its clearance
rate) may allow the development of sustained release curcumin dosage forms as a
practical approach to cancer chemoprevention.
PMID- 28417447
TI - Air leak without subcutaneous emphysema in an adult patient due to thyroidectomy.
PMID- 28417448
TI - DECISION-CTO: A "negative" clinical trial? Really?
PMID- 28417449
TI - Citicoline: pharmacological and clinical review, 2016 update.
AB - This review is based on the previous one published in 2010 -Secades JJ.
Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol 2011; 52
(Suppl 2): S1-62-, incorporating 183 new references, having all the information
available to facilitate the access to the information in one document. This
review is focused on the main indications of the drug, as acute stroke and its
sequelae, including the cognitive impairment, and traumatic brain injury and its
sequelae. There are retrieved the most important experimental and clinical data
in both indications.
PMID- 28417450
TI - Exploring the biological activity of condensed tannins and nutritional value of
tree and shrub leaves from native species of the Argentinean Dry Chaco.
AB - BACKGROUND: Tropical tree or shrub leaves are an important source of nutrients
for ruminants and a potential source of biologically active compounds that may
affect ruminal metabolism of nutrients. Therefore, eight woody species from the
native flora of Argentinean Dry Chaco, rich in secondary compounds such as
condensed tannins (CT), were assessed for their nutritional value, CT fractions
and in vitro true digestibility of dry matter, as well as biological activity
(BA). RESULTS: Differences among species were found in contents of total phenol,
protein-precipitating phenols (PPP), bound proteins to PPP (BP) and BP/PPP (P <
0.0001). The BP/PPP ratio reveals differences among species in potential BA as
indicated by protein precipitation. The major CT of each species were isolated
and purified for use as a standard. Although Schinopsis balansae had the most (P
<= 0.05) total CT (19.59% DM), Caesalpinia paraguariensis had greater (P <= 0.05)
BA with the most PPP (530.21% dry matter). Larrea divaricata, at 0.97, followed
by Acacia aroma, at 0.89, had CT with the highest (P <= 0.05) BP/PPP ratios,
followed by Prosopis alba (0.59). CONCLUSION: There were differences in nutritive
value and bioactivity among species. Those with the greatest CT were not
necessarily those with the most BA. Caesalpinia paraguariensis, S. balansae and
L. divaricata were the most promising species as native forage CT sources.
Cercidiurm praecox (20.87% CP; 18.14% acid detergent fiber) and Prosopis nigra
(19.00% CP; 27.96% acid detergent fiber) showed the best (P <= 0.05) nutritive
values. According to their nutritive traits, these species might be complementary
in grass-based ruminant diets. (c) 2017 Society of Chemical Industry.
PMID- 28417451
TI - Prophylactic anti-staphylococcal antibiotics for cystic fibrosis.
AB - BACKGROUND: Staphylococcus aureus causes pulmonary infection in young children
with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent
such infection and lung damage. Antibiotics have adverse effects and long-term
use might lead to infection with Pseudomonas aeruginosa. This is an update of a
previously published review. OBJECTIVES: To assess continuous oral antibiotic
prophylaxis to prevent the acquisition of Staphylococcus aureus versus no
prophylaxis in people with cystic fibrosis, we tested these hypotheses.
Prophylaxis:1. improves clinical status, lung function and survival;2. causes
adverse effects (e.g. diarrhoea, skin rash, candidiasis);3. leads to fewer
isolates of common pathogens from respiratory secretions;4. leads to the
emergence of antibiotic resistance and colonisation of the respiratory tract with
Pseudomonas aeruginosa. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis
and Genetic Disorders Group Trials Register, comprising references identified
from comprehensive electronic database searches, handsearches of relevant
journals and abstract books of conference proceedings. Companies manufacturing
anti-staphylococcal antibiotics were contacted.Most recent search of the Group's
Register: 29 September 2016. SELECTION CRITERIA: Randomised trials of continuous
oral prophylactic antibiotics (given for at least one year) compared to
intermittent antibiotics given 'as required', in people with cystic fibrosis of
any disease severity. DATA COLLECTION AND ANALYSIS: The authors assessed studies
for eligibility and methodological quality and extracted data. MAIN RESULTS: We
included four studies, with a total of 401 randomised participants aged zero to
seven years on enrolment; one study is ongoing. The two older included studies
generally had a higher risk of bias across all domains, but in particular due to
a lack of blinding and incomplete outcome data, than the two more recent studies.
We only regarded the most recent study as being generally free of bias, although
even here we were not certain of the effect of the per protocol analysis on the
study results. Evidence was downgraded based on GRADE assessments and outcome
results ranged from moderate to low quality. Downgrading decisions were due to
limitations in study design (all outcomes); for imprecision (number of people
needing additional antibiotics); and for inconsistency (weight z score).Fewer
children receiving anti-staphylococcal antibiotic prophylaxis had one or more
isolates of Staphylococcus aureus (low quality evidence). There was no
significant difference between groups in infant or conventional lung function
(moderate quality evidence). We found no significant effect on nutrition (low
quality evidence), hospital admissions, additional courses of antibiotics (low
quality evidence) or adverse effects (moderate quality evidence). There was no
significant difference in the number of isolates of Pseudomonas aeruginosa
between groups (low quality evidence), though there was a trend towards a lower
cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at
two and three years and towards a higher rate from four to six years. As the
studies reviewed lasted six years or less, conclusions cannot be drawn about the
long-term effects of prophylaxis. AUTHORS' CONCLUSIONS: Anti-staphylococcal
antibiotic prophylaxis leads to fewer children having isolates of Staphylococcus
aureus, when commenced early in infancy and continued up to six years of age. The
clinical importance of this finding is uncertain. Further research may establish
whether the trend towards more children with CF with Pseudomonas aeruginosa,
after four to six years of prophylaxis, is a chance finding and whether choice of
antibiotic or duration of treatment might influence this.
PMID- 28417452
TI - Worldwide pattern of antibiotic prescription in endodontic infections.
AB - BACKGROUND: Odontogenic infections, and especially endodontic infections, are
polymicrobial, involving a combination of Gram-positive and Gram-negative
facultative anaerobes and strictly anaerobic bacteria. Therefore, antibiotics can
be used as an adjunct to endodontic treatment. However, most chronic and even
acute endodontic infections can be successfully managed by disinfection of the
root-canal system, which eliminates the source of infection, followed by abscess
drainage or tooth extraction, without the need for antibiotics. The literature
provides evidence of inadequate prescribing practices by dentists. The aim of
this concise review was to analyse the worldwide pattern of antibiotic
prescription in endodontic infections. METHODS: Comprehensive searches were
conducted in MEDLINE/PubMed, Wiley Online Database, Web of Science and Scopus.
The databases were searched up to 13 March 2016 for studies in which dentists
used systemic antibiotics to treat endodontic lesions and which reported data on
the type of antibiotic prescribed and on the diagnosis of the endodontic disease
treated. RESULTS: The electronic and hand searches identified 69 titles, of which
25 were included in the final analysis. Amoxicillin was reported as the drug of
choice for endodontic infections in most countries, and clindamycin and
erythromycin were the choice for patients allergic to penicillin. Dentists
worldwide prescribe antibiotics for non-indicated conditions, such as pulpitis.
CONCLUSION: Antibiotics are overprescribed for the management of endodontic
infections. It is necessary to improve antibiotic-prescribing habits in the
treatment of endodontic infections, as well as to introduce educational
initiatives to encourage the coherent and proper use of antibiotics in such
conditions.
PMID- 28417453
TI - Bilateral cataract surgery with intraocular lens implant in a captive western
lowland gorilla.
AB - We report a case of bilateral cataract surgery performed in a 21-year-old western
lowland gorilla. Phacoemulsification with intraocular lens insertion was
performed using standard human surgical equipment. Visual function significantly
improved. She subsequently mated and gave birth. Ultimately, cataract surgery
enabled the birth of a baby gorilla.
PMID- 28417454
TI - Prevalence and predictors of anxiety in an African sample of recent stroke
survivors.
AB - OBJECTIVES: Studies considering emotional disturbances in the setting of stroke
have primarily focused on depression and been conducted in high-income countries.
Anxiety in stroke survivors, which may be associated with its own unique sets of
risk factors and clinical parameters, has been rarely investigated in sub-Saharan
Africa (SSA). We assess the characteristics of anxiety and anxiety-depression
comorbidity in a SSA sample of recent stroke survivors. MATERIALS AND METHODS: We
assessed baseline data being collected as part of an intervention to improve one
year blood pressure control among recent (<=1 month) stroke survivors in SSA.
Anxiety in this patient population was measured using the Hospital Anxiety and
Depression Scale (HADS), while the community screening instrument for dementia
was used to evaluate cognitive functioning. Independent associations were
assessed using logistic regression analysis. RESULTS: Among 391 participants,
clinically significant anxiety (HADS anxiety score>=11) was found in 77 (19.7%).
Anxiety was comorbid with depression in 55 (14.1%). Female stroke survivors were
more likely than males to have anxiety (OR=2.4, 95% CI=1.5-4.0). Anxiety was
significantly associated with the presence of cognitive impairment after
adjusting for age, gender and education (OR=6.8, 95% CI=2.6-18.0). CONCLUSIONS:
One in five recent stroke survivors in SSA has clinically significant anxiety,
and well over 70% of those with anxiety also have depression. Future studies will
need to determine what specific impact post-stroke anxiety may have on post
stroke clinical processes and outcomes.
PMID- 28417455
TI - An efficient process for obtaining prebiotic oligosaccharides derived from
lactulose using isomerized and purified whey permeate.
AB - BACKGROUND: One of the most promising uses of whey permeate (WP) is the synthesis
of prebiotic oligosaccharides. Herein, commercial WP was submitted to chemical
isomerization catalysed by sodium borate at an alkaline pH and subsequent
purification using anion-exchange resins to remove boron. Subsequently, purified
mixtures were used to synthesize prebiotic oligosaccharides using beta
galactosidase from Bacillus circulans. RESULTS: Isomerization of concentrated WP
(200 g L-1 lactose) gave rise to levels of lactulose up to 155.5 g L-1 after 30
min of reaction (molar ratio of boron/lactose, 1/1; pH 12; 70 degrees C). Boron
was removed from the isomerized WP (IWP) using the combination of a strong acid
(IR-120, H+ ) and a weak base (IRA-743) anion-exchange resins, reducing its level
to <1 ppm, without loss of lactulose. During the transglycosylation reaction of
purified IWP (lactose/lactulose ratio, 1/2.4) maximum content of prebiotic
compounds was achieved, i.e. 690 g kg-1 WP after 3 h of reaction. CONCLUSION:
This study shows that combined chemical-enzymatic reactions together with the
purification of IWP results in an efficient synthesis of prebiotic
oligosaccharides. (c) 2017 Society of Chemical Industry.
PMID- 28417456
TI - Interventions to improve adherence to inhaled steroids for asthma.
AB - BACKGROUND: Despite its proven efficacy in improving symptoms and reducing
exacerbations, many patients with asthma are not fully adherent to their steroid
inhaler. Suboptimal adherence leads to poorer clinical outcomes and increased
health service utilisation, and has been identified as a contributing factor to a
third of asthma deaths in the UK. Reasons for non-adherence vary, and a variety
of interventions have been proposed to help people improve treatment adherence.
OBJECTIVES: To assess the efficacy and safety of interventions intended to
improve adherence to inhaled corticosteroids among people with asthma. SEARCH
METHODS: We identified trials from the Cochrane Airways Trials Register, which
contains studies identified through multiple electronic searches and handsearches
of other sources. We also searched trial registries and reference lists of
primary studies. We conducted the most recent searches on 18 November 2016.
SELECTION CRITERIA: We included parallel and cluster randomised controlled trials
of any duration conducted in any setting. We included studies reported as full
text articles, those published as abstracts only and unpublished data. We
included trials of adults and children with asthma and a current prescription for
an inhaled corticosteroid (ICS) (as monotherapy or in combination with a long
acting beta2-agonist (LABA)). Eligible trials compared an intervention primarily
aimed at improving adherence to ICS versus usual care or an alternative
intervention. DATA COLLECTION AND ANALYSIS: Two review authors screened the
searches, extracted study characteristics and outcome data from included studies
and assessed risk of bias. Primary outcomes were adherence to ICS, exacerbations
requiring at least oral corticosteroids and asthma control. We graded results and
presented evidence in 'Summary of findings' tables for each comparison.We
analysed dichotomous data as odds ratios, and continuous data as mean differences
or standardised mean differences, all using a random-effects model. We described
skewed data narratively. We made no a priori assumptions about how trials would
be categorised but conducted meta-analyses only if treatments, participants and
the underlying clinical question were similar enough for pooling to make sense.
MAIN RESULTS: We included 39 parallel randomised controlled trials (RCTs)
involving adults and children with asthma, 28 of which (n = 16,303) contributed
data to at least one meta-analysis. Follow-up ranged from two months to two years
(median six months), and trials were conducted mainly in high-income countries.
Most studies reported some measure of adherence to ICS and a variety of other
outcomes such as quality of life and asthma control. Studies generally were at
low or unclear risk of selection bias and at high risk of biases associated with
blinding. We considered around half the studies to be at high risk for attrition
bias and selective outcome reporting.We classified studies into four comparisons:
adherence education versus control (20 studies); electronic trackers or reminders
versus control (11 studies); simplified drug regimens versus usual drug regimens
(four studies); and school-based directly observed therapy (three studies). Two
studies are described separately.All pooled results for adherence education,
electronic trackers or reminders and simplified regimens showed better adherence
than controls. Analyses limited to studies using objective measures revealed that
adherence education showed a benefit of 20 percentage points over control (95%
confidence interval (CI) 7.52 to 32.74; five studies; low-quality evidence);
electronic trackers or reminders led to better adherence of 19 percentage points
(95% CI 14.47 to 25.26; six studies; moderate-quality evidence); and simplified
regimens led to better adherence of 4 percentage points (95% CI 1.88 to 6.16;
three studies; moderate-quality evidence). Our confidence in the evidence was
reduced by risk of bias and inconsistency.Improvements in adherence were not
consistently translated into observable benefit for clinical outcomes in our
pooled analyses. None of the intervention types showed clear benefit for our
primary clinical outcomes - exacerbations requiring an oral corticosteroid (OCS)
(evidence of very low to low quality) and asthma control (evidence of low to
moderate quality); nor for our secondary outcomes - unscheduled visits (evidence
of very low to moderate quality) and quality of life (evidence of low to moderate
quality). However, some individual studies reported observed benefits for OCS and
use of healthcare services. Most school or work absence data were skewed and were
difficult to interpret (evidence of low quality, when graded), and most studies
did not specifically measure or report adverse events.Studies investigating the
possible benefit of administering ICS at school did not measure adherence,
exacerbations requiring OCS, asthma control or adverse events. One study showed
fewer unscheduled visits, and another found no differences; data could not be
combined. AUTHORS' CONCLUSIONS: Pooled results suggest that a variety of
interventions can improve adherence. The clinical relevance of this improvement,
highlighted by uncertain and inconsistent impact on clinical outcomes such as
quality of life and asthma control, is less clear. We have low to moderate
confidence in these findings owing to concerns about risk of bias and
inconsistency. Future studies would benefit from predefining an evidence-based
'cut-off' for acceptable adherence and using objective adherence measures and
validated tools and questionnaires. When possible, covert monitoring and some
form of blinding or active control may help disentangle effects of the
intervention from effects of inclusion in an adherence trial.
PMID- 28417457
TI - Effects of riboflavin and ultraviolet light treatment on platelet thrombus
formation and thrombus stability on collagen.
AB - BACKGROUND: Pathogen reduction technologies (PRTs) are considered for the
implementation of safer platelet (PLT) transfusion. PRT treatment involves the
addition of a photosensitizer to a blood component followed by ultraviolet (UV)
light irradiation. However, the effects of PRT treatment on PLT thrombus
formation and thrombus stability have not been satisfactorily clarified. STUDY
DESIGN AND METHODS: Leukoreduced PLT concentrates (PCs) were treated with
riboflavin and UV light (Mirasol PRT). PLT thrombus formation on collagen was
evaluated by the microchannel method, by which the total amount of PLTs deposited
was measured as indices of thrombus formation and thrombus stability. Using a
cone-plate shear-induced PLT aggregometer, PLT reactivity in blood flow was
examined in a wide range of shear stresses of 6 to 108 dyn/cm2 . RESULTS: There
was no significant difference in surface coverage between PRT-treated PLTs and
control PLTs on collagen. On the other hand, the total amount of PRT-treated PLTs
deposited was higher than that of control PLTs. The promotive effect of PRT
treatment on PLT deposition completely disappeared in the presence of tirofiban,
a potent integrin alphaIIbbeta3 inhibitor. The percentage of the dissociation of
PRT-treated PLTs on collagen was lower than that of control PLTs after flushing
with phosphate-buffered saline. PRT treatment significantly inhibited PLT
aggregation under high-shear-stress conditions. CONCLUSION: Riboflavin-based PRT
treatment of PCs leads to the enhancement of PLT thrombus formation and thrombus
stability on collagen. However, it does not enhance the reactivity of PLTs not in
contact with collagen under high-shear-stress conditions.
PMID- 28417458
TI - Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3.
AB - Resistin, a proinflammatory cytokine, is elevated in a number of pathological
disorders, including cancer. The serum resistin level in colon cancer patients is
elevated and correlates with tumor grade. However, the implications of increased
resistin on colon cancer cells remain unclear. In the present study, we find that
resistin binds to TLR4 on colon cancer cell membrane and initiates TLR4-MyD88
dependent activation of ERK. In addition, the upregulation of SOCS3 by ERK
downregulates the JAK2/TAT3 pathway and causes the arrest of cells in G1 phase.
Interestingly, we observe that resistin-exposed cells survive 5-fluorouracil
treatment because of a decrease in drug uptake due to the arrest of cells in G1
phase.
PMID- 28417459
TI - Does obesity complicate regional anesthesia and result in longer decision to
delivery time for emergency cesarean section?
AB - BACKGROUND: Maternal obesity can cause problems with anesthesia and surgery which
may be reflected in emergency cesarean sections (CS) as an increased decision-to
delivery interval (DDI). AIM: To study the association of elevated maternal BMI
with DDI and the failure of regional anesthesia. METHODS: Eight hundred and forty
two consecutive emergency CSs during a period of 1 year in a tertiary hospital
were studied retrospectively. DDIs were analyzed in Crash and < 30-min urgency
categories (n = 528), while the time required to establish regional anesthesia
and its success were analyzed for all emergency CS cases. RESULTS: The urgency
distribution of the CSs was 11%, 52%, and 37% in Crash, < 30-min, and > 30-min
urgency categories respectively. Increased BMI was associated with longer DDI
time in the < 30-min urgency category (33(13-176) vs. 38(18-118) min; P < 0.05
for BMI < 30 and > 35 group respectively). Regional anesthesia failures (new
regional anesthesia, conversion to general anesthesia, or complaint of pain
during surgery) took place in 3.7%, 6.8%, and 8.5% in the BMI < 30, 30-35, and >
35 groups respectively (P = 0.021). Epidural top-up resulted in shorter DDI and
time delay between arrival at the operating room and skin incision across all
urgency and BMI groups than combined spinal epidural (CSE) anesthesia.
CONCLUSION: Higher BMI was associated with longer DDI and more regional
anesthesia failures. Epidural top-up was faster than CSE for establishing CS
anesthesia.
PMID- 28417460
TI - Effect of high-fat diet and growth stage on the diversity and composition of
intestinal microbiota in healthy bovine livestock.
AB - BACKGROUND: This study aimed to investigate the composition of bacteria in the
bovine rectum and their functions during growth, in relation to different diets.
Fecal samples were collected from 6-, 12-, 18- and 24-month cattle fed high-fat
diet, and healthy female parents fed regular diet. Total DNA was amplified (V3-V4
of 16S rRNA) and submitted to barcode-DNA pyrosequencing. Intestinal microbiota
profiles and functions were then analyzed. RESULTS: A total of 114 512
operational taxonomic units were detected from the 1 802 243 sequences obtained.
In 6-month-old and female parent groups, the top three abundant phyla were
Bacteroidetes (37.6%, 32.2%), Firmicutes (34.4%, 48.2%) and Proteobacteria (9.1%,
6.3%); in the 12-, 18- and 24-month groups, they were Proteobacteria (45.5%,
47.1%, 38.8%), Firmicutes (27.4%, 22.2%, 20.1%) and Bacteroidetes (14.9%, 19.4%,
17.7%), respectively. Paludibacter and Desulfopila in abundance showed negative
(P < 0.001) and positive (P < 0.05) correlation, respectively, to cattle weight
gain through metagenomic functional prediction of methane, cysteine and
methionine metabolism. Meanwhile, cofactor/vitamin and amino acid metabolic
processes were significantly higher in bacteria from the regular diet group than
high-fat diet groups, with markedly lower cellular processes and signaling, and
reduced glycan biosynthesis and metabolism (P < 0.01). CONCLUSIONS: The 6-month
cattle and female parents shared similar intestinal bacteria; the community
structure of fecal microbiota was significantly affected by high-fat diet in
older cattle. (c) 2017 Society of Chemical Industry.
PMID- 28417461
TI - The pathway intermediate 2-keto-3-deoxy-L-galactonate mediates the induction of
genes involved in D-galacturonic acid utilization in Aspergillus niger.
AB - In Aspergillus niger, the enzymes encoded by gaaA, gaaB, and gaaC catabolize d
galacturonic acid (GA) consecutively into l-galactonate, 2-keto-3-deoxy-l
galactonate, pyruvate, and l-glyceraldehyde, while GaaD converts l-glyceraldehyde
to glycerol. Deletion of gaaB or gaaC results in severely impaired growth on GA
and accumulation of l-galactonate and 2-keto-3-deoxy-l-galactonate, respectively.
Expression levels of GA-responsive genes are specifically elevated in the ?gaaC
mutant on GA as compared to the reference strain and other GA catabolic pathway
deletion mutants. This indicates that 2-keto-3-deoxy-l-galactonate is the inducer
of genes required for GA utilization.
PMID- 28417462
TI - Exploring patient satisfaction levels, self-rated oral health status and
associated variables among citizens covered for dental insurance through a
National Social Security Scheme in India.
AB - OBJECTIVE: To assess patient satisfaction, self-rated oral health and associated
factors, including periodontal status and dental caries, among patients covered
for dental insurance through a National Social Security Scheme in New Delhi,
India. METHOD: A total of 1,498 patients participated in the study. Satisfaction
levels and self-rated oral-health scores were measured using a questionnaire
comprising 12 closed-ended questions. Clinical data were collected using the
Community Periodontal Index (CPI) and the decayed, missing and filled teeth
(DMFT) index. Regression analysis was conducted to evaluate factors associated
with dental caries, periodontal status and self-rated oral health. RESULTS: Areas
of concern included poor cleanliness within the hospital, extensive delays for
appointments, waiting time in hospital and inadequate interpersonal and
communication skills among health-care professionals. Approximately 51% of the
respondents rated their oral health as fair to poor. Younger age, no tobacco
usage, good periodontal status and absence of dental caries were significantly
associated with higher oral health satisfaction, with odds ratios of 3.94, 2.38,
2.58 and 2.09, respectively (P <= 0.001). CONCLUSION: The study indicates poor
satisfaction levels with the current dental care system and a poor self-rated
oral health status among the study population. Some specific areas of concern
have been identified. These findings may facilitate restructuring of the existing
dental services under the National Social Security Scheme towards creating a
better patient care system.
PMID- 28417463
TI - Pharmacological interventions for primary sclerosing cholangitis: an attempted
network meta-analysis.
AB - BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease
that is associated with both hepatobiliary and colorectal malignancies, which can
result in liver cirrhosis and its complications. The optimal pharmacological
treatment for patients with primary sclerosing cholangitis remains controversial.
OBJECTIVES: To assess the comparative benefits and harms of different
pharmacological interventions in people with primary sclerosing cholangitis by
performing a network meta-analysis, and to generate rankings of available
pharmacological interventions according to their safety and efficacy. Given that
it was not possible to assess whether potential effect modifiers were similar
across comparisons, we did not perform the network meta-analysis but instead used
standard Cochrane methods.When trials begin to provide an adequate description of
potential effect modifiers, we will attempt to conduct network meta-analysis.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index -
Expanded, the WHO International Clinical Trials Registry Platform, and randomised
controlled trials registers until February 2017 to identify randomised clinical
trials (RCT) on pharmacological interventions for primary sclerosing cholangitis.
SELECTION CRITERIA: We included only RCTs, irrespective of language, blinding, or
publication status, in which participants were given a diagnosis of primary
sclerosing cholangitis. We excluded trials that included previously liver
transplanted participants. We considered any of various pharmacological
interventions compared with one other or with placebo. We excluded trials that
compared different doses of various pharmacological interventions or that
reported different treatment durations, except for ursodeoxycholic acid (UDCA).
As UDCA is the drug most commonly investigated for primary sclerosing
cholangitis, we performed a second analysis in which we stratified the dose of
UDCA. DATA COLLECTION AND ANALYSIS: We calculated the odds ratio and the rate
ratio with 95% confidence intervals (CIs) using both fixed-effect and random
effects models based on available-participant analysis with Review Manager. We
assessed risk of bias according to Cochrane, controlled risk of random errors
with Trial Sequential Analysis, and assessed the quality of the evidence using
GRADE. MAIN RESULTS: We identified 22 RCTs in which 1211 participants were
randomised to 13 different interventions. Most were placebo-controlled trials.
Trials had few restrictions apart from an established diagnosis of primary
sclerosing cholangitis, evidence of cholestasis, absence of decompensated liver
disease, and absence of malignancy. However, some trials included symptomatic
participants only, and others included both symptomatic and asymptomatic
participants. A total of 11 RCTs (706 participants) provided data for one or more
outcomes. The period of follow-up ranged from three months to three years in most
trials. Only three trials reported follow-up longer than three years.
Investigators found no evidence of differences in important clinical benefits
such as reduction in mortality at maximal follow-up and improvement in health
related quality of life. Primary outcomes Mortality: Effect estimates: colchicine
versus placebo: odds ratio 0.44, 95% CI 0.04 to 5.07, participants = 84, one
trial; penicillamine versus placebo: odds ratio 1.18, 95% CI 0.39 to 3.58,
participants = 70, one trial; steroids versus placebo: odds ratio 3.00, 95% CI
0.10 to 90.96, participants = 11, one trial; ursodeoxycholic acid versus placebo:
odds ratio 1.51, 95% CI 0.63 to 3.63, participants = 348, two trials, I2 = 0%;
vancomycin versus placebo: not estimable because no events in either group,
participants = 29, one trial. Serious adverse events (proportion): Effect
estimates: infliximab versus placebo: odds ratio not estimable (because of zero
events in both arms), participants = 7, one trial; steroids versus placebo: odds
ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; vancomycin
versus placebo: not estimable because no events in either group, participants =
29, one trial. Serious adverse events (number): Effect estimates: infliximab
versus placebo: rate ratio 0.80, 95% CI 0.02 to 40.44, participants = 7, one
trial; penicillamine versus placebo: rate ratio 13.60, 95% CI 0.78 to 237.83,
participants = 70, one trial; steroids versus placebo: rate ratio 3.32, 95% CI
0.71 to 15.62, participants = 11, one trial. Adverse events (proportion): Effect
estimates: steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90,
participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio
1.22, 95% CI 0.68 to 2.17, participants = 198, one trial; vancomycin versus
placebo: not estimable because no events in either group, participants = 29, one
trial. Adverse events (number): Effect estimates: cyclosporin versus placebo:
rate ratio 2.64, 95% CI 0.99 to 7.03, participants = 26, one trial; steroids
versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one
trial; ursodeoxycholic acid plus metronidazole versus ursodeoxycholic acid: rate
ratio 2.36, 95% CI 0.98 to 5.71, participants = 71, one trial. Health-related
quality of life: ursodeoxycholic acid versus placebo: mean difference 1.30, 95%
CI -5.61 to 8.21, participants = 198, one trial (Short Form (SF)-36 General
Health Scale). Secondary outcomes Studies provided no evidence of differences in
clinical benefits such as a reduction in the requirement for liver
transplantation or a reduction in the incidence proportion of cholangiocarcinoma.
One small trial (29 participants) comparing vancomycin versus placebo reported no
malignancies, no liver decompensation, and no liver transplantation in either
group after a very short follow-up period of 12 weeks after treatment. None of
the remaining trials clearly reported other clinical benefits such as decreased
development of all malignancies, colorectal cancer, liver decompensation, time to
liver decompensation, time to liver transplantation, or requirement for
cholecystectomy to allow comparisons between different interventions. SOURCE OF
FUNDING: Fifteen trials reported the source of funding; three were funded by
parties without vested interest in results of the trial, and 12 were funded in
part or in full by drug companies. AUTHORS' CONCLUSIONS: Evidence is currently
insufficient to show differences in effectiveness measures such as mortality,
health-related quality of life, cirrhosis, or liver transplantation between any
active pharmacological intervention and no intervention. However, trials were at
high risk of bias and included small numbers of participants, had short follow-up
periods, and reported few clinical outcomes. An urgent need exists to identify an
effective medical treatment for primary sclerosing cholangitis through well
designed RCTs with adequate follow-up that aim to identify differences in
outcomes important to people with primary sclerosing cholangitis.
PMID- 28417464
TI - Qualitative and quantitative analysis of endophyte alkaloids in perennial
ryegrass using near-infrared spectroscopy.
AB - BACKGROUND: Near-infrared reflectance spectroscopy (NIRS) has been widely used in
forage quality control because it is faster, cleaner and less expensive than
conventional chemical procedures. In Lolium perenne (perennial ryegrass), one of
the most important forage grasses, the infection by asymptomatic Epichloe fungal
endophytes alters the plant nutritional quality due to the production of
alkaloids. In this research, we developed a rapid method based on NIRS to detect
and quantify endophyte alkaloids (peramine, lolitrem B and ergovaline) using a
heterogeneous set of L. perenne plants obtained from wild grasslands and
cultivars. RESULTS: NIR spectra from dried grass samples were recorded and
classified according to the absence or presence of alkaloids, based on reference
methods. The best discriminant equations for detection of alkaloids classified
correctly 94.4%, 87.5% and 92.9% of plants containing peramine, lolitrem B and
ergovaline, respectively. The quantitative NIR equations obtained by modified
partial least squares (MPLS) algorithm had coefficients of correlation of 0.93,
0.41, and 0.76 for peramine, lolitrem B and ergovaline respectively. CONCLUSION:
NIRS is a suitable tool for qualitative analysis of endophyte alkaloids in
grasses and for the accurate quantification of peramine and ergovaline. (c) 2017
Society of Chemical Industry.
PMID- 28417465
TI - Effects of rare sugar d-allulose on heat-induced gelation of surimi prepared from
marine fish.
AB - BACKGROUND: d-Allulose (Alu), the C3-epimer of d-fructose, is a non-caloric
sweetener (0.39 kcal g-1 ) with a suppressive effect on postprandial blood
glucose elevation. The aim of this study was to investigate the effects of Alu
used as a sweetener and gel improver instead of sucrose on heat-induced gelation
of surimi. RESULTS: The puncture test of a heat-induced surimi gel showed that
with 50 g kg-1 Alu the gel had 15% and 6% higher gel strength than the
corresponding gel with sucrose (Suc) and with sorbitol (Sor), respectively. In
addition, Alu-gel had 26% and 25% higher water-holding capacity (WHC) than Suc-
and Sor-gel. Heating of myofibrillar protein with Alu, unlike Suc and Sor,
facilitated the formation of both disulfide and non-disulfide crosslinks that
might be associated with the mechanical properties and WHC of Alu-gel.
CONCLUSION: Alu improves the mechanical properties and WHC of the heat-induced
surimi gel. Furthermore, Alu is low in calories compared with Suc (4.0 kcal g-1 )
and Sor (3.0 kcal g-1 ). Thus Alu will be an alternative of Suc or Sor for
developing surimi-based products with health benefits. (c) 2017 Society of
Chemical Industry.
PMID- 28417466
TI - S-nitrosoglutathione spraying improves stomatal conductance, Rubisco activity and
antioxidant defense in both leaves and roots of sugarcane plants under water
deficit.
AB - Water deficit is a major environmental constraint on crop productivity and
performance and nitric oxide (NO) is an important signaling molecule associated
with many biochemical and physiological processes in plants under stressful
conditions. This study aims to test the hypothesis that leaf spraying of S
nitrosoglutathione (GSNO), an NO donor, improves the antioxidant defense in both
roots and leaves of sugarcane plants under water deficit, with positive
consequences for photosynthesis. In addition, the roles of key photosynthetic
enzymes ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and
phosphoenolpyruvate carboxylase (PEPC) in maintaining CO2 assimilation of GSNO
sprayed plants under water deficit were evaluated. Sugarcane plants were sprayed
with water or GSNO 100 MUM and subjected to water deficit, by adding polyethylene
glycol (PEG-8000) to the nutrient solution. Sugarcane plants supplied with GSNO
presented increases in the activity of antioxidant enzymes such as superoxide
dismutase in leaves and catalase in roots, indicating higher antioxidant capacity
under water deficit. Such adjustments induced by GSNO were sufficient to prevent
oxidative damage in both organs and were associated with better leaf water
status. As a consequence, GSNO spraying alleviated the negative impact of water
deficit on stomatal conductance and photosynthetic rates, with plants also
showing increases in Rubisco activity under water deficit.
PMID- 28417467
TI - Retraction Statement: CXCL12/CXCR4 chemokine signaling in spinal glia induces
pain hypersensitivity through MAPKs-mediated neuroinflammation in bone cancer
rats.
AB - 'CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity
through MAPKs-mediated neuroinflammation in bone cancer rats' by Hu X.-M., Liu Y.
N., Zhang H.-L., Cao S.-B., Zhang T., Chen L.-P. and Shen W. The above article
from Journal of Neurochemistry, published online on 26 January 2015 and in volume
132, issue 4, pages 452-463 (available through www.onlinelibrary.wiley.com), and
its subsequent Corrigendum, published online on 5 February 2015 and in volume
132, issue 4, p. 487, have been retracted by agreement between the Journal's
Editor-in-Chief, Jorg Schulz, corresponding author Wen Shen on behalf of the
authors, and John Wiley & Sons Ltd. The retraction has been agreed as the same
GFAP immunostaining image was used to represent different experimental conditions
in two different publications (Shen et al. [2014] in the Journal of
Neuroinflammation and Hu et al. [2015] in the Journal of Neurochemistry), with
apparent brightness changes between the images. Shen et al. (2014) show in the
outer right panel of Figure 4a, as well as in Fig. 8A for the GFAP/sham
condition, a GFAP immunostaining after treatment with TCI + Fluorocitrate. The
same image, at a lower intensity, is used in Hu et al. (2015) in the first panel
of figure 5b as a sham control. The shape of the tissue margins of the spinal
cord section as well as several landmark epitopes that point towards identical
images are encircled: Shen et al. 2014 Figure 4a Hu et al. 2015 Figure 5b Shen et
al. 2014 Figure 8a The authors confirmed that 'The research published in JNC
sequentially builds on our previous study published in Journal of
Neuroinflammation, as we have mentioned in the discussion. So, at the beginning,
we performed these experiments and wrote these two manuscripts together,' whereas
the statements in the Hu et al. paper, 'The testing procedure was performed
according to previously standardized protocols (Hargreaves et al. 1988) and our
published report (Shen et al. 2014) ... confirmed our previous report (Shen et
al. 2014)' imply that the Hu et al. study was a follow-up based on a new original
data set. The authors were given the opportunity to respond and to provide the
original raw images. Several Sham group GFAP immunostainings were sent. However,
the reliability of the data that was presented in the publication could not be
confirmed and the paper is therefore being retracted. A corrigendum related to a
different problem with data representation that was previously issued for this
paper is also being retracted (Hu et al. 2015, Corrigendum). References Hu X. M.,
Liu Y. N., Zhang H. L., Cao S. B., Zhang T., Chen L. P. and Shen W. (2015a)
CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity
through MAPKS-mediated neuroinflammation in bonce cancer rats. J. Neurochem. 132,
452-463. doi:10.1111/jnc.12985. Hu X. M., Liu Y. N., Zhang H. L., Cao S. B.,
Zhang T., Chen L. P. and Shen W. (2015b) Corrigendum. J. Neurochem. 132, 487.
doi:10.1111/jnc.13054. Shen W., Hu X. M., Liu Y. N., Han Y., Chen L. P., Wang C.
C. and Song C. (2014) CXCL12 in astrocytes contributes to bone cancer pain
through CXCR4-mediated neuronal sensitization and glial activation in rat spinal
cord. J. Neuroinflammation 11, 75. doi:10.1186/1742-2094-11-75.
PMID- 28417468
TI - Corrigendum.
PMID- 28417469
TI - Oesophageal involvement in 26 consecutive patients with mucous membrane
pemphigoid.
AB - BACKGROUND: Oesophageal involvement of mucous membrane pemphigoid (MMP) has not
yet been thoroughly described. OBJECTIVES: To characterize systematically the
endoscopic lesions of a series of patients with oesophageal symptoms seen at a
referral centre for autoimmune bullous diseases. METHODS: Clinical, endoscopic
and immunological findings of consecutively referred patients with MMP with
oesophageal involvement, systemic and endoscopic treatments, and follow-up are
described. RESULTS: Of 477 consecutive patients with MMP consulting between 2002
and 2012, 26 (5.4%) had symptomatic oesophageal involvement. Dysphagia, observed
in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could
be the first sign of MMP. Patients with oesophageal involvement had a mean of
three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients
had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s)
and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal
symptom relief for five patients. Dilatation was combined with systemic therapy
for 12 patients and was successful in nine; one perforation occurred.
CONCLUSIONS: Symptomatic oesophageal involvement affected 5.4% of patients with
MMP. Dermatologists and gastroenterologists should be aware of these
mucocutaneous diseases and their oesophageal involvement, as it could lead to
earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic
option for symptomatic stricture not relieved by optimized systemic therapy
alone.
PMID- 28417470
TI - Stress, death, and the biological glue of sinking matter.
PMID- 28417471
TI - Assessing the impact of selection bias on test decisions in trials with a time-to
event outcome.
AB - If past treatment assignments are unmasked, selection bias may arise even in
randomized controlled trials. The impact of such bias can be measured by
considering the type I error probability. In case of a normally distributed
outcome, there already exists a model accounting for selection bias that permits
calculating the corresponding type I error probabilities. To model selection bias
for trials with a time-to-event outcome, we introduce a new biasing policy for
exponentially distributed data. Using this biasing policy, we derive an exact
formula to compute type I error probabilities whenever an F-test is performed and
no observations are censored. Two exemplary settings, with and without random
censoring, are considered in order to illustrate how our results can be applied
to compare distinct randomization procedures with respect to their performance in
the presence of selection bias. (c) 2017 The Authors. Statistics in Medicine
Published by John Wiley & Sons Ltd.
PMID- 28417472
TI - Evaluation of Liver, Kidney, and Spleen Elasticity in Healthy Newborns and
Infants Using Shear Wave Elastography.
AB - OBJECTIVES: Elasticity measurements of tissues can be valuable in the diagnosis
and management of various diseases. The aim of this study was to determine the
elasticity values for normal liver, kidney, and spleen of healthy newborns and
infants using shear wave elastography (SWE) imaging. METHODS: A total of 50
healthy term newborns and infants (19 girls and 31 boys; mean age 20.1 days,
range 1 to 70 days) were examined by an experienced pediatric radiologist using
SWE. None of them had any liver, kidney or spleen disease, or any other systemic
disease that could affect these organs secondarily. All newborns and infants had
a normal abdominal ultrasound scan. RESULTS: Age, sex, weight, height, and body
mass index had no significant effects on shear wave velocity (SWV) values of
liver and spleen. The SWV values of both kidneys decreased with age, weight,
height, and body mass index. The mean SWV values were 1.70 m/s (range: 1.23-2.43
m/s) for the liver, 1.69 m/s (range: 0.8-2.40 m/s) for the right kidney, 1.70 m/s
(range: 0.9-2.49 m/s) for the left kidney, and 2.03 m/s (range: 1.28-2.48 m/s)
for the spleen. CONCLUSIONS: Shear wave elastography can be used to measure
liver, kidney, and spleen elasticity in newborns and infants. The standard values
for abdominal organs allow differentiation of healthy versus pathological tissue.
We measured the normal values of SWE in healthy newborns and infants as reference
data.
PMID- 28417473
TI - Ophthalmology patients' interest in online access to clinic notes at three US
clinics.
AB - PURPOSE: This study aimed to understand patients' perceptions about potential
benefits and harms of accessing their own ophthalmology clinic notes via an
electronic patient portal as part of the OpenNotes initiative. METHODS: The
authors conducted a cross-sectional, in-person survey of ophthalmology patients
at three US eye clinics. The paper survey was self-administered or administered
with assistance from study staff before or after patients' clinical visits. The
authors used descriptive statistics to summarise patient characteristics and
patient attitudes about accessing their ophthalmology notes online. Chi-square
and t-tests were performed to assess differences in patient responses between
clinic locations. RESULTS: Four hundred and fifty-one patients responded
(response rate 65%). Most patients thought that accessing doctors' notes online
was a good idea (95%), wanted to view their clinic notes online (94%), and agreed
online access would increase their understanding of their eye problems (95%) and
help them better remember their care plan (94%); 14% said online access would
increase their worry; 43% had privacy concerns; and 96% indicated they would show
or discuss their notes with at least one other person. Non-white patients were
more likely than white patients to perceive online clinic notes as a useful tool,
but they were also more likely to worry and to express greater privacy concerns.
CONCLUSIONS: Patients at three US eye clinics were strongly in favour of online
access to ophthalmology notes and were optimistic this access would improve their
understanding and self-care. Ophthalmologists should consider offering online
access to their notes to enhance doctor-patient communication and improve
clinical outcomes.
PMID- 28417474
TI - First-Trimester Sonographic Evaluation of Palatine Clefts: A Novel Diagnostic
Approach.
AB - OBJECTIVES: Sonographic evaluation of the palate is a difficult task, and most
palatine clefts are diagnosed in the neonatal period because of the limitations
of 2-dimensional (2D) sonography. The objective is to describe a sonographic
technique based on 2D markers for screening of palatine clefts during the nuchal
translucency scan and to assess the ability of 3-dimensional (3D) sonography in
imaging the normal and abnormal palate. METHODS: A total of 2014 women who
enrolled for first-trimester screening were included in this prospective study.
Screening for palatine clefts was done by 2D evaluation of bony landmarks of the
palate, which were the appearance of the palatal line in the sagittal view,
retronasal triangle in the coronal view, and alveolar ridge of the maxilla in the
axial view followed, by 3D evaluation in suspicious cases. All cases included in
the study were followed by second-trimester anomaly scans and evaluated
postnatally. Additionally, in 100 consecutive normal cases, 3D evaluation of the
palate was done. RESULTS: Visualization of 2D landmarks could be done in all, and
3D assessment was feasible in 94% of cases. Fourteen cases, of which 5 were
unilateral, 4 bilateral, and 2 median cleft lip and palate, 2 median cleft
palate, and 1 atypical palatine cleft were identified. There were no false
positives results reported, and 1 case of a bifid uvula was missed. CONCLUSIONS:
The study demonstrates that evaluation of the palate can be done at the 11 to 14
week scan based on 2D markers and can also be assessed with 3D sonography. The
inclusion of 2D markers in all 3 planes increases the sensitivity for detection
of palatine clefts.
PMID- 28417475
TI - The Role of Early Gestation Ultrasound in the Assessment of Fetal Anatomy in
Maternal Obesity.
AB - OBJECTIVES: The 2012 Eunice Kennedy Shriver National Institute of Child Health
fetal imaging consensus suggested that fetal anatomy ultrasound in obese
pregnancies be performed at 20 to 22 weeks, with follow-up in 2 to 4 weeks if
anatomy is incomplete. It was postulated that imaging in early gestation may
improve visualization, although no prospective trials had been done to date.
METHODS: We performed a prospective longitudinal blinded trial comparing an early
gestation ultrasound (13 + 0 to 15 + 6 weeks) with the traditional second
trimester ultrasound for completion of the fetal anatomy survey in obese
patients. Inclusion criteria included singleton gestation, body mass index (BMI)
more than 30, less than 16 + 0 weeks' gestation, and no karyotype abnormality;
exclusion criteria included age younger than 18 years, more than 16 weeks'
gestation at time of consent, and BMI less than 30. Participants received a
transvaginal and/or transabdominal sonogram for fetal anatomic survey at 13 + 0
to 15 + 6 weeks' gestation (US1). Images from US1 were blinded to physicians and
sonographers performing subsequent examinations. All participants underwent the
traditional transabdominal sonogram at 18 to 24 weeks (US2). If US2 failed to
complete the anatomic survey, a repeat transabdominal sonogram (2-US2) was
performed 2 to 4 weeks later. RESULTS: A total of 152 pregnancies met the
criteria. Anatomy completion rate was 57.2% for US1 and 62.5% for US2, which was
not statistically significant, even when stratified by BMI. Excluding the
philtrum, the US1 performed better than US2 for class III obesity (65.5% versus
45.5% [P = .035]). Combination of US1 + US2 yielded a higher completion rate than
US2 + 2-US2 (94.1% versus 83.6% [P = .0023]). CONCLUSIONS: In the setting of
maternal obesity, the addition of an ultrasound in early gestation may be of
highest benefit for patients with class III obesity (BMI > 40 kg/m2 ).
PMID- 28417476
TI - Clindamycin-associated acute generalized exanthematous pustulosis.
AB - WHAT IS KNOWN AND THE OBJECTIVE: Acute generalized exanthematous pustulosis
(AGEP) is a rare, severe cutaneous reaction that usually occurs following
medication exposure. Clindamycin has rarely been linked to dermatologic side
effects, including AGEP. CASE SUMMARY: This report details the case of a patient
who developed AGEP with vancomycin and clindamycin use. After discontinuing
clindamycin, the rash improved significantly. WHAT IS NEW AND CONCLUSION: Timely
management of adverse skin reactions to antibiotics is paramount, and early
identification of the culprit agent can allow for an alternative agent to be
utilized. Clindamycin should be considered a potential causative agent for
patients with skin reactions.
PMID- 28417477
TI - A flexible family of transformation cure rate models.
AB - In this paper, we introduce a flexible family of cure rate models, mainly
motivated by the biological derivation of the classical promotion time cure rate
model and assuming that a metastasis-competent tumor cell produces a detectable
tumor mass only when a specific number of distinct biological factors affect the
cell. Special cases of the new model are, among others, the promotion time
(proportional hazards), the geometric (proportional odds), and the negative
binomial cure rate model. In addition, our model generalizes specific families of
transformation cure rate models and some well-studied destructive cure rate
models. Exact likelihood inference is carried out by the aid of the
expectationUmaximization algorithm; a profile likelihood approach is exploited
for estimating the parameters of the model while model discrimination problem is
analyzed by the aid of the likelihood ratio test. A simulation study demonstrates
the accuracy of the proposed inferential method. Finally, as an illustration, we
fit the proposed model to a cutaneous melanoma data-set. Copyright (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28417478
TI - Point-of-Care Lung Sonography: An Audit of 1150 Examinations.
AB - OBJECTIVES: Point-of-care lung sonography has theoretical usefulness in numerous
diseases; however clinical indications and the impact of this technique have not
been fully investigated. We aimed to describe the current use of point-of-care
lung sonography. METHODS: A 2-year prospective observational study was performed
by pulmonologists in an Italian university hospital. Techniques, indications,
consequences of lung sonography, and barriers to the examination were analyzed.
RESULTS: A total of 1150 lung sonographic examinations were performed on 951
patients. The most common indications were diagnosis and follow-up of pleural
effusion in 361 cases (31%), evaluation of lung consolidation (322 [28%]), acute
heart failure (195 [17%]), guide to pleural procedures (117 [10%]), pneumothorax
(54 [5%]) and acute exacerbations of chronic obstructive pulmonary disease (30
[3%]). The mean duration of the examination +/- SD was 6 +/- 4 minutes. The
transducers most frequently used were convex (746 [65%]) and linear (161 [14%]),
whereas in 205 examinations (18%), both transducers were used. According to the
judgment of the caring clinician, 51% of the examinations were clinically
relevant. CONCLUSIONS: Point-of-care lung sonography performed by pulmonologists
is quick and feasible and could be widely used for different clinical indications
with a potentially high clinical impact. The widespread use of this technique may
have a relevant clinical impact in several indications.
PMID- 28417479
TI - ACCP Template for Evaluating a Clinical Pharmacist.
AB - ACCP is committed to ensuring that clinical pharmacists possess the competencies
necessary to deliver comprehensive medication management in team-based, direct
patient care environments. These competencies are divided into six essential
domains: direct patient care, pharmacotherapy knowledge, systems-based care and
population health, communication, professionalism, and continuing professional
development. The 2016 ACCP Clinical Practice Affairs Committee has developed an
evaluation tool that includes the assessable tasks of today's clinical
pharmacists that fall within each domain. This instrument can be used by
institutions, organizations, and others responsible for clinical pharmacist
performance evaluation and professional development.
PMID- 28417480
TI - Efficient Red Perovskite Light-Emitting Diodes Based on Solution-Processed
Multiple Quantum Wells.
AB - This paper reports a facile and scalable process to achieve high performance red
perovskite light-emitting diodes (LEDs) by introducing inorganic Cs into multiple
quantum well (MQW) perovskites. The MQW structure facilitates the formation of
cubic CsPbI3 perovskites at low temperature, enabling the Cs-based QWs to provide
pure and stable red electroluminescence. The versatile synthesis of MQW
perovskites provides freedom to control the crystallinity and morphology of the
emission layer. It is demonstrated that the inclusion of chloride can further
improve the crystallization and consequently the optical properties of the Cs
based MQW perovskites, inducing a low turn-on voltage of 2.0 V, a maximum
external quantum efficiency of 3.7%, a luminance of ~440 cd m-2 at 4.0 V. These
results suggest that the Cs-based MQW LED is among the best performing red
perovskite LEDs. Moreover, the LED device demonstrates a record lifetime of over
5 h under a constant current density of 10 mA cm-2 . This work suggests that the
MQW perovskites is a promising platform for achieving high performance visible
range electroluminescence emission through high-throughput processing methods,
which is attractive for low-cost lighting and display applications.
PMID- 28417481
TI - Chemical Reduction of Intrinsic Defects in Thicker Heterojunction Planar
Perovskite Solar Cells.
AB - Minimization of defects in absorber materials is essential for hybrid perovskite
solar cells, especially when constructing thick polycrystalline layers in a
planar configuration. Here, a simple methylamine solution-based additive is
reported to improve film quality with nearly an order of magnitude reduction in
intrinsic defect concentration. In the resultant film, an increase in carrier
lifetime as a result of a decrease in shallow electronic disorder is observed.
This superior crystalline film quality is further evidenced via a doubled spin
relaxation time as compared with other reports. Bearing sufficient carrier
diffusion length, a thick absorber layer (~650 nm) is implemented in planar
devices to achieve a champion power conversion efficiency of 20.02% with a
stabilized output efficiency of 19.01% under one sun illumination. This work
demonstrates a simple approach to improve hybrid perovskite film quality by
substantial reduction of intrinsic defects for wide applications in
optoelectronics.
PMID- 28417482
TI - Hall Effect in Bulk-Doped Organic Single Crystals.
AB - The standard technique to separately and simultaneously determine the carrier
concentration per unit volume (N, cm-3 ) and the mobility (MU) of doped inorganic
single crystals is to measure the Hall effect. However, this technique has not
been reported for bulk-doped organic single crystals. Here, the Hall effect in
bulk-doped single-crystal organic semiconductors is measured. A key feature of
this work is the ultraslow co-deposition technique, which reaches as low as 10-9
nm s-1 and enables us to dope homoepitaxial organic single crystals with
acceptors at extremely low concentrations of 1 ppm. Both the hole concentration
per unit volume (N, cm-3 ) and the Hall mobility (MUH ) of bulk-doped rubrene
single crystals, which have a band-like nature, are systematically observed. It
is found that these rubrene single crystals have (i) a high ionization rate and
(ii) scattering effects because of lattice disturbances, which are peculiar to
this organic single crystal.
PMID- 28417483
TI - Primary repair of complete sternal cleft associated with absent anterior
pericardium.
PMID- 28417484
TI - Well-differentiated neuroendocrine tumors in skin: Terminology and diagnostic
utility of cytokeratin 5/6 and p63.
AB - BACKGROUND: Well-differentiated neuroendocrine tumors (WDNETs) in skin include
metastases from visceral primary sites and very uncommonly, primary cutaneous
carcinoid tumors. Cutaneous WDNET may present a diagnostic challenge and in
particular can be mistaken for a benign skin adnexal tumor. In contrast to
cutaneous adnexal tumors, metastatic adenocarcinomas to the skin are cytokeratin
5/6 (CK5/6) and p63 negative in the majority of cases. It is unclear if failure
to stain with CK5/6 and p63 would be helpful in differentiating WDNETs from
cutaneous adnexal neoplasms. METHODS: We reviewed 10 cases of cutaneous WDNETs (8
cases of metastatic disease and 2 presumed primary carcinoid tumors of the skin)
and performed immunohistochemical stains for CK5/6 and p63 on all cases. RESULTS:
All 10 cases were negative with both CK5/6 and p63. CONCLUSION: Negative staining
for CK5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal
neoplasms. It is important to consider WDNETs in the differential diagnosis of
cutaneous adnexal neoplasms as low-grade tumors may be the first sign of
aggressive metastatic disease.
PMID- 28417485
TI - Tumor Microenvironment-Triggered Supramolecular System as an In Situ
Nanotheranostic Generator for Cancer Phototherapy.
AB - The efficacy of photosensitizers in cancer phototherapy is often limited by
photobleaching, low tumor selectivity, and tumor hypoxia. Assembling
photosensitizers into nanostructures can improve photodynamic therapy efficacy
and the safety profile of photosensitizers. Herein by employing supramolecular
assembly, enhanced theranostic capability of Mn2+ -assisted assembly of a
photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor
environment-triggered coassembly strategy is further developed to form Mn/DVDMS
nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a
highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7
cells and xenograft tumors, MnO2 /DVDMS is reduced by glutathione (GSH) and H2 O2
and reassembled into nanoDVD, which can be monitored by activated magnetic
resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH,
the production of O2 , and the formation of nanoDVD are shown to be synergistic
with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a
new avenue for cancer theranostics.
PMID- 28417486
TI - Age-specific function of alpha5beta1 integrin in microglial migration during
early colonization of the developing mouse cortex.
AB - Microglia, the immune cells of the central nervous system, take part in brain
development and homeostasis. They derive from primitive myeloid progenitors that
originate in the yolk sac and colonize the brain mainly through intensive
migration. During development, microglial migration speed declines which suggests
that their interaction with the microenvironment changes. However, the matrix
cell interactions allowing dispersion within the parenchyma are unknown.
Therefore, we aimed to better characterize the migration behavior and to assess
the role of matrix-integrin interactions during microglial migration in the
embryonic brain ex vivo. We focused on microglia-fibronectin interactions
mediated through the fibronectin receptor alpha5beta1 integrin because in vitro
work indirectly suggested a role for this ligand-receptor pair. Using 2-photon
time-lapse microscopy on acute ex vivo embryonic brain slices, we found that
migration occurs in a saltatory pattern and is developmentally regulated. Most
importantly, there is an age-specific function of the alpha5beta1 integrin during
microglial cortex colonization. At embryonic day (E) 13.5, alpha5beta1
facilitates migration while from E15.5, it inhibits migration. These results
indicate a developmentally regulated function of alpha5beta1 integrin in
microglial migration during colonization of the embryonic brain.
PMID- 28417487
TI - Reducing Interfacial Resistance between Garnet-Structured Solid-State Electrolyte
and Li-Metal Anode by a Germanium Layer.
AB - Substantial efforts are underway to develop all-solid-state Li batteries (SSLiBs)
toward high safety, high power density, and high energy density. Garnet
structured solid-state electrolyte exhibits great promise for SSLiBs owing to its
high Li-ion conductivity, wide potential window, and sufficient thermal/chemical
stability. A major challenge of garnet is that the contact between the garnet and
the Li-metal anodes is poor due to the rigidity of the garnet, which leads to
limited active sites and large interfacial resistance. This study proposes a new
methodology for reducing the garnet/Li-metal interfacial resistance by depositing
a thin germanium (Ge) (20 nm) layer on garnet. By applying this approach, the
garnet/Li-metal interfacial resistance decreases from ~900 to ~115 Omega cm2 due
to an alloying reaction between the Li metal and the Ge. In agreement with
experiments, first-principles calculation confirms the good stability and
improved wetting at the interface between the lithiated Ge layer and garnet. In
this way, this unique Ge modification technique enables a stable cycling
performance of a full cell of lithium metal, garnet electrolyte, and LiFePO4
cathode at room temperature.
PMID- 28417488
TI - Electroactive Ionic Soft Actuators with Monolithically Integrated Gold
Nanocomposite Electrodes.
AB - Electroactive ionic gel/metal nanocomposites are produced by implanting
supersonically accelerated neutral gold nanoparticles into a novel chemically
crosslinked ion conductive soft polymer. The ionic gel consists of chemically
crosslinked poly(acrylic acid) and polyacrylonitrile networks, blended with
halloysite nanoclays and imidazolium-based ionic liquid. The material exhibits
mechanical properties similar to that of elastomers (Young's modulus ~ 0.35 MPa)
together with high ionic conductivity. The fabrication of thin (~100 nm thick)
nanostructured compliant electrodes by means of supersonic cluster beam
implantation (SCBI) does not significantly alter the mechanical properties of the
soft polymer and provides controlled electrical properties and large surface area
for ions storage. SCBI is cost effective and suitable for the scaleup
manufacturing of electroactive soft actuators. This study reports the high-strain
electromechanical actuation performance of the novel ionic gel/metal
nanocomposites in a low-voltage regime (from 0.1 to 5 V), with long-term
stability up to 76 000 cycles with no electrode delamination or deterioration.
The observed behavior is due to both the intrinsic features of the ionic gel
(elasticity and ionic transport capability) and the electrical and morphological
features of the electrodes, providing low specific resistance (<100 Omega cm-2 ),
high electrochemical capacitance (~mF g-1 ), and minimal mechanical stress at the
polymer/metal composite interface upon deformation.
PMID- 28417489
TI - Management of Septic emboli in patients with infectious endocarditis.
AB - BACKGROUND AND AIM: Septic emboli (SE) associated with infectious endocarditis
(IE) can result in splenic abscesses and infectious intracranial aneurysms (IIA).
We investigated the impact of SE on patient outcomes following surgery for IE.
METHOD: From January-2000 to October-2015, all patients with surgical IE (n =
437) were evaluated for incidence and management of SE. RESULTS: Overall SE was
found in 46/437 (10.52%) patients (n = 17 spleen, 13 brain, and 16 both). No
mortality was seen in the brain emboli groups, but in the splenic abscess group
the in-hospital mortality was 8.69% (n = 4); and was associated with Age >35 (OR
= 2.63, 1.65-4.20) and congestive heart failure (OR = 14.40, 1.23-168.50).
Patients with splenic emboli had excellent mid-term outcome following discharge
(100% survival at 4-years). Splenic emboli requiring splenectomy was predicted by
a >20 mm valve vegetation (OR = 1.37, 1.056-1.77) and WBC >12000 cells/mm (OR =
5.58, 1.2-26.3). No patient with streptococcus-viridians infection had a
nonviable spleen (OR = 0.67, 0.53-0.85). Postoperative acute-kidney-injury was
higher in the splenectomy group (45.45% vs 9%) (p = 0.027). There were 6 patients
with symptomatic IIAs that required coiling/clipping which was associated with
age <30 years, (OR = 6.09, 1.10-33.55). Survival in patients with cerebral emboli
decreased to 78% at 3-4 years. Patients with both splenic and brain emboli had a
92% survival rate at 1-year and 77% at 2-4 years. CONCLUSION: Septic emboli is
common in endocarditis patients. Patients with high preoperative WBC level and
large valve vegetations require CT imaging of the spleen. Both spleen and brain
interventions in the setting of IE can be performed safely with excellent early
and mid-term outcomes.
PMID- 28417490
TI - Myocardial bridge of the left anterior descending artery.
PMID- 28417491
TI - Giant inferior vena cava aneurysm.
PMID- 28417492
TI - Editorial: CT-P13, a biosimilar of anti-tumour necrosis factor-alpha agent
(infliximab), in inflammatory bowel diseases.
PMID- 28417493
TI - Editorial: clinical benefits of vitamin D therapy in inflammatory bowel disease.
PMID- 28417494
TI - Editorial: CT-P13, a biosimilar of anti-tumour necrosis factor-alpha agent
(infliximab), in inflammatory bowel diseases - authors' reply.
PMID- 28417495
TI - Letter: chronic hepatitis C genotype 3 infection - still a hurdle toward a direct
acting anti-viral-induced HCV cure?
PMID- 28417496
TI - Editorial: accumulating data about ustekinumab in refractory Crohn's disease in
real world experience.
PMID- 28417497
TI - Editorial: importance of definition of inflammatory bowel disease and an
increased incidence in children.
PMID- 28417498
TI - Editorial: Clostridium difficile and inflammatory bowel disease - is it always a
bad combination?
PMID- 28417499
TI - Editorial: inflammatory bowel disease risk reduction after migration - are early
life events important?
PMID- 28417500
TI - Editorial: hepatitis B reactivation in patients with chronic hepatitis C treated
with direct-acting antivirals - incidence, severity of hepatitis and lessons to
learn.
PMID- 28417501
TI - D-dimer level, in association with humoral responses, negatively correlates with
survival of porcine islet grafts in non-human primates with immunosuppression.
AB - BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft
survival in non-human primates (NHPs) after porcine islet transplantation (PITx),
but their success rates vary. To understand the mechanism of graft loss, we
investigated the relationships between graft survival and humoral or inflammatory
responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from
adult wild-type pigs were intraportally transplanted into streptozotocin-induced
diabetic rhesus monkeys. Three monkeys received an IS regimen without anti-CD154
monoclonal antibody (mAb, transplant [Tpl]-control) and 11 received IS with anti
CD154 mAb (Tpl-aCD154). Blood samples were obtained weekly from the recipients
until graft function ceased and weekly from three healthy monkeys (non-Tpl
control) for 6 months. Levels of D-dimer, C-reactive protein (CRP), and anti
Galalpha1,3Gal (Gal) IgG, IgG1, IgG2, and IgM were measured. Liver biopsy
sections were immunostained for fibrin, insulin, and human CD31. RESULTS: Tpl
control monkeys had higher time-weighted average levels (levelstwavrg ) of
Deltaanti-Gal IgG (Delta, difference from level at day 0) and D-dimer than Tpl
aCD154 or non-Tpl-control. The levelstwavrg of Deltaanti-Gal IgG, IgG1, IgG2, and
IgM did not differ between Tpl-aCD154 and non-Tpl-control. The levelstwavrg of D
dimer and Deltaanti-Gal IgG2 negatively correlated with graft survival. Liver
biopsy sections revealed many spots of fibrin deposition inside islet grafts that
were well vascularized by human CD31-positive cells. Level of D-dimer positively
correlated with Deltaanti-Gal IgG1 in Tpl-control and with Deltaanti-Gal IgG2 in
Tpl-aCD154. CONCLUSIONS: Intravascular coagulation, in association with immune
responses against xenografts, may partly contribute to loss of islet grafts in
NHPs after PITx.
PMID- 28417502
TI - A Quinonoid-Imine-Enriched Nanostructured Polymer Mediator for Lithium-Sulfur
Batteries.
AB - The reversible formation of chemical bonds has potential for tuning multi
electron redox reactions in emerging energy-storage applications, such as lithium
sulfur batteries. The dissolution of polysulfide intermediates, however, results
in severe shuttle effect and sluggish electrochemical kinetics. In this study,
quinonoid imine is proposed to anchor polysulfides and to facilitate the
formation of Li2 S2 /Li2 S through the reversible chemical transition between
protonated state (?NH+ ?) and deprotonated state (?N?). When serving as the
sulfur host, the quinonoid imine-doped graphene affords a very tiny shuttle
current of 2.60 * 10-4 mA cm-2 , a rapid redox reaction of polysulfide, and
therefore improved sulfur utilization and enhanced rate performance. A high areal
specific capacity of 3.72 mAh cm-2 is achieved at 5.50 mA cm-2 on the quinonoid
imine-doped graphene based electrode with a high sulfur loading of 3.3 mg cm-2 .
This strategy sheds a new light on the organic redox mediators for reversible
modulation of electrochemical reactions.
PMID- 28417503
TI - Robotic resection of giant left ventricular myxoma causing outflow tract
obstruction.
AB - We report a 38-year-old female, who presented with progressive dyspnea and
fatigue. Echocardiography revealed a giant and freely mobile left ventricular
myxoma causing left ventricular outflow tract (LVOT) obstruction. The patient
underwent totally endoscopic robotic excision of a giant left ventricular myxoma.
The tumor was completely removed through the mitral valve orifice with a left
atriotomy incision.
PMID- 28417504
TI - The coping function of mental disorder symptoms: is it to be considered when
developing diagnostic criteria for behavioural addictions?
PMID- 28417505
TI - 300% Enhancement of Carrier Mobility in Uniaxial-Oriented Perovskite Films Formed
by Topotactic-Oriented Attachment.
AB - Organic-inorganic perovskites with intriguing optical and electrical properties
have attracted significant research interests due to their excellent performance
in optoelectronic devices. Recent efforts on preparing uniform and large-grain
polycrystalline perovskite films have led to enhanced carrier lifetime up to
several microseconds. However, the mobility and trap densities of polycrystalline
perovskite films are still significantly behind their single-crystal
counterparts. Here, a facile topotactic-oriented attachment (TOA) process to grow
highly oriented perovskite films, featuring strong uniaxial-crystallographic
texture, micrometer-grain morphology, high crystallinity, low trap density (~4 *
1014 cm-3 ), and unprecedented 9 GHz charge-carrier mobility (71 cm2 V-1 s-1 ),
is demonstrated. TOA-perovskite-based n-i-p planar solar cells show minimal
discrepancies between stabilized efficiency (19.0%) and reverse-scan efficiency
(19.7%). The TOA process is also applicable for growing other state-of-the-art
perovskite alloys, including triple-cation and mixed-halide perovskites.
PMID- 28417506
TI - The effect of intraoperative hypothermia upon blood transfusion needs and length
of stay among gastrointestinal system cancer surgery.
AB - This cross-sectional study was performed to evaluate the relationship between
intraoperative body temperature and the need for blood transfusion and length of
stay in the post-anaesthetic care unit (PACU) or in the intensive care unit (ICU)
among 79 patients undergoing elective oncology surgery of the digestive system.
There was a statistically significant correlation between a lower temperature
during surgery and medical diagnosis (p = .009), the use of bupivacaine
anaesthesia (p = .016), anaesthesia time (p = .003) and anaesthesia type (p =
.033), surgery time (p = .021) and surgery type (p = .002), volumes infused
during the intraoperative period (p = .006), admission to the ICU (p = .032) and
length of stay in PACU (p = .029). The lower the temperature when the patient is
admitted to the operating room, the lower the temperature during the procedure (p
? .001). There was no association between the body temperature of patients and
blood transfusion (p = .619). Hypothermia was associated with increased length of
stay in the PACU, but was not associated with the need for blood transfusion
during the intra- and postoperative periods. The use of preoperative passive
warming methods allows patients to reach the operating room hypothermic.
PMID- 28417507
TI - Understanding the roots of health inequalities requires new methods.
PMID- 28417508
TI - Effectiveness of semi-permeable dressings to treat radiation-induced skin
reactions. A systematic review.
AB - The aim of this systematic review is to assess the available evidence concerning
the effectiveness of semi-permeable dressings, on the full range of skin
reactions, related to radiation therapy in cancer patients, from local erythema
to moist desquamation, including subjective symptoms such as pain, discomfort,
itchiness, burning and the effect on daily life activities. The bibliographic
search was carried out looking for Randomised Clinical Trials (RCTs) indexed in
PubMed, Cinhal, Cochrane plus and Biblioteca Nacional de Salud, published in the
English and Spanish language, between 2010 and 2015. Data extraction and
evaluation of study quality was undertaken by peer reviewers using the Critical
Appraisal Skills Programme (CASP). Of 181 studies, nine full texts were assessed.
Finally, six RCT were included in the final synthesis: three analysed the
application of Mepilex(r) Lite in breast cancer and head & neck cancer; one
evaluated the application of Mepitel(r) Film in breast cancer; and two assessed
the use of silver nylon dressings in breast cancer and in patients with lower
gastrointestinal cancer. The results show that semi-permeable dressings are
beneficial in the management of skin toxicity related to radiation therapy.
However, rigorous trials showing stronger evidence are needed.
PMID- 28417509
TI - A biomolecular recognition approach for the functionalization of cellulose with
gold nanoparticles.
AB - Materials with new and improved functionalities can be obtained by modifying
cellulose with gold nanoparticles (AuNPs) via the in situ reduction of a gold
precursor or the deposition or covalent immobilization of pre-synthesized AuNPs.
Here, we present an alternative biomolecular recognition approach to
functionalize cellulose with biotin-AuNPs that relies on a complex of 2
recognition elements: a ZZ-CBM3 fusion that combines a carbohydrate-binding
module (CBM) with the ZZ fragment of the staphylococcal protein A and an anti
biotin antibody. Paper and cellulose microparticles with AuNPs immobilized via
the ZZ-CBM3:anti-biotin IgG supramolecular complex displayed an intense red
color, whereas essentially no color was detected when AuNPs were deposited over
the unmodified materials. Scanning electron microscopy analysis revealed a
homogeneous distribution of AuNPs when immobilized via ZZ-CBM3:anti-biotin IgG
complexes and aggregation of AuNPs when deposited over paper, suggesting that
color differences are due to interparticle plasmon coupling effects. The approach
could be used to functionalize paper substrates and cellulose nanocrystals with
AuNPs. More important, however, is the fact that the occurrence of a biomolecular
recognition event between the CBM-immobilized antibody and its specific, AuNP
conjugated antigen is signaled by red color. This opens up the way for the
development of simple and straightforward paper/cellulose-based tests where
detection of a target analyte can be made by direct use of color signaling.
PMID- 28417510
TI - Morphology Tunable Hybrid Carbon Nanosheets with Solvatochromism.
AB - The tunable photoluminescence of carbon-based nanomaterials has received much
attention for a wide range of applications. Herein, a unique, broad
solvatochromic hybrid carbon nanosheet (CNS) synthesized through the hydrothermal
carbonization of molecular precursors exploiting graphene oxide as a template is
reported, resulting in the formation of clusters of carbon nanorings on the
surface of graphene-oxide nanosheets. Under UV and visible-light excitation, the
hybrid CNS exhibits tunable emission spanning the wide range of colors in a
series of solvents with different polarities. This interesting spectroscopic
behavior is found to originate from hydrogen-bonding interactions between CNS and
solvents, which eventually induce the morphological transition of CNS from 2D
sheets to 3D crumpled morphologies, affecting the lifetimes of emissive states.
This novel soft carbon nanostructure may open up a new possibility in tailoring
the photophysical properties of carbon nanomaterials.
PMID- 28417511
TI - Algal supplementation of vegetarian eating patterns improves plasma and serum
docosahexaenoic acid concentrations and omega-3 indices: a systematic literature
review.
AB - BACKGROUND: Vegetarians are likely to have lower intakes of preformed
docosahexaenoic acid (DHA) than omnivorous populations who consume fish and
animal products. As such, vegetarian populations have omega-3 indices up to 60%
lower than those who consume marine products. Algae, the primary producer of DHA
in the marine food chain, offer an alternative source of DHA for those who do not
consume marine or animal products. This systematic review aims to examine the
evidence for the relationship between supplementation with algal forms of DHA and
increased DHA concentrations in vegetarian populations. METHODS: The SCOPUS,
Science Direct and Web of Science scientific databases were searched to identify
relevant studies assessing the effect of algal DHA consumption by vegetarian
(including vegan) populations. RESULTS: Four randomised controlled trials and two
prospective cohort studies met the inclusion criteria. All included studies
reported algal sources of DHA significantly improve DHA concentrations (including
plasma, serum, platelet and red blood cell fractions), as well as omega-3
indices, in vegetarian populations. An evident time or dose response was not
apparent given the small number of studies to date. CONCLUSIONS: Future studies
should address long chain n-3 polyunsaturated fatty acid deficiencies in
vegetarian populations using algal DHA and explore the potential physiological
and health improvements in these individuals.
PMID- 28417512
TI - Na2 Ti3 O7 @N-Doped Carbon Hollow Spheres for Sodium-Ion Batteries with Excellent
Rate Performance.
AB - Uniform Na2 Ti3 O7 hollow spheres assembled from N-doped carbon-coated ultrathin
nanosheets are synthesized. A unique multilayer structure of nanosheets is
presumed to significantly reduce energy consumption during the diffusion process
of sodium ions, while the carbon-coated structure can increase the overall
conductivity. The as-prepared sample used as an anode in sodium-ion batteries
exhibits the best rate performance ever reported for Na2 Ti3 O7 , delivering more
than 60 mAh g-1 after 1000 continuous cycles at the high rate of 50 C, which was
achieved due to its unique structure.
PMID- 28417513
TI - Repair of a coronary artery aneurysm in close proximity to the left main trunk.
PMID- 28417514
TI - Enlarged Cavum Septi Pellucidi and Vergae in the Fetus: A Cause for Concern.
AB - OBJECTIVES: To investigate fetal cases identified at our institution to determine
whether an enlarged cavum septi pellucidi or cavum vergae is associated with
other fetal abnormalities and whether its presence warrants more detailed
investigation of the fetus. METHODS: In a retrospective study, 15 high- and low
risk patients undergoing prenatal sonography who had an enlarged cavum septi
pellucidi or cavum vergae identified were reviewed. Data were collected for the
sonographic study indication, gestation age at diagnosis of a prominent cavum,
and associated anomalies. Follow-up outcome data regarding further imaging,
karyotype, diagnosis of brain anomaly, and associated congenital abnormalities
were obtained. RESULTS: Fifteen patients met the inclusion criteria. Nine
patients were identified as having a prominent cavum septi pellucidi, and 6 were
identified as having a prominent cavum vergae. The mean gestational age +/- SD
was 22.7 +/- 5.9 weeks. Eleven patients made it to delivery. Of the 15 patients,
4 were thought to have trisomy 21, and 13 had congenital anomalies. Outcomes
included 10 major adverse outcomes, 4 cases with normal development or minor
abnormalities, and 1 lost to follow-up. An isolated dilated cavum on prenatal
sonography was seen in 5 cases: 1 with lissencephaly on a neonatal examination, 3
premature deliveries (1 demise, 1 hospice, and 1 normal), and 1 unknown.
CONCLUSIONS: Our cohort had many associated clinical anomalies: 3 confirmed
trisomy 21 and 1 probable trisomy 21, 2 genetic disorders, and 10 major adverse
outcomes, 5 of which were grave. Although we studied a small cohort, we conclude
that an enlarged cavum septi pellucidi or cavum vergae warrants consideration of
genetic counseling, which may include noninvasive prenatal testing (cell-free
DNA), amniocentesis with microarray testing, or both.
PMID- 28417515
TI - Do maternal depression and anxiety influence children's oral health-related
quality of life?
AB - OBJECTIVE: This study aimed to investigate the influence of depressive and
anxiety symptoms in young mothers on their perception in relation to their
children's oral health-related quality of life (COHRQoL). METHODS: This cross
sectional study was carried out in Pelotas, Southern Brazil, and it was nested in
a cohort of adolescent mothers having their prenatal care in public health
service, starting in 2008. When the children were aged 24-36 months, they and
their mothers were interviewed and submitted to clinical examination by a trained
team. Socioeconomic, educational, behavioural and psychological assessments were
collected in the interview and oral examination investigated caries and gingival
bleeding (in mothers) and caries and dental trauma (in children). Maternal
perception of impact on COHRQoL was evaluated by Early Childhood Oral Health
Impact Scale (ECOHIS). The outcome in the present study was the occurrence of
impact on COHRQoL (ECOHIS>=2), that is the presence of at least one ECOHIS item
reported as occasionally (score 2), often (score 3) or very often (score 4).
Analysis was conducted using Poisson regression with robust variance and obtained
prevalence ratios (PR) and respective 95% confidence intervals (CI). RESULTS:
This study comprised 537 mother-child dyads. After adjustment, higher scores of
COHRQoL remained significantly associated with depressive symptoms (PR=1.80, 95%
CI: 1.36-2.38) and maternal anxiety symptoms (PR=2.28, 95% CI: 1.72-3.00).
Mothers with anxiety symptoms or depressive symptoms had a prevalence of impact
91% higher when compared with mothers without any symptoms (PR=1.91; CI 95% 1.35
2.68), and mothers with both symptoms had almost 2.5 times higher risk of
perception of negative impact on COHRQoL (PR=2.48; CI 95% 1.78-3.45). CONCLUSION:
Poorer COHRQoL was associated with maternal depression and anxiety symptoms.
PMID- 28417516
TI - Discovering What Matters: Interrogating Clinician Responses to Ethics
Consultation.
AB - Against the background assumptions that (a) knowing what clinical ethics
consultation represents to those with whom ethics consultants work most closely
is a necessary component for being responsible in the practice of ethics
consultation, and (b) the complexities of soliciting and understanding colleague
evaluations require another inherent responsibility for the methods by which
ethics consultations are evaluated, in this article we report our experience
soliciting, analyzing, and trying to understand retrospective evaluations of our
Clinical Ethics Consultation Service. These evaluations were collected through a
quality assessment effort at our institution. Drawing from the qualitative
elements of our survey instrument, we describe unexpected variations among the
requests for ethics consultation and the retrospective reports from those
colleagues making the requests. Focusing on just one aspect - the reason for
request - raised several core questions about how we should evaluate those
retrospective reports, what could be learned from the differences that we were
now encountering, and what we could learn about the process of evaluating our
practices. Working through these questions, we suggest several issues to consider
in ongoing efforts to describe and evaluate clinical ethics consultation: the
role of time and memory in evaluating retrospective evaluations, the importance
of attending to the language of moral shift or disruption with which our
colleagues describe their experiences, and how to understand the role of ethics
consultation in creating 'moral space' (a la Margaret Urban Walker's conception)
for colleagues to process their moral experiences.
PMID- 28417517
TI - Evaluating Clinical Ethics Support: A Participatory Approach.
AB - The current process towards formalization within evaluation research, in
particular the use of pre-set standards and the focus on predefined outcomes,
implies a shift of ownership from the people who are actually involved in real
clinical ethics support services (CESS) in a specific context to external
stakeholders who increasingly gain a say in what 'good CESS' should look like.
The question is whether this does justice to the insights and needs of those who
are directly involved in actual CESS practices, be it as receivers or providers.
We maintain that those actually involved in concrete CESS practices should also
be involved in its evaluation, not only as respondents, but also in setting the
agenda of the evaluation process and in articulating the criteria by which CESS
is evaluated. Therefore, we propose a participatory approach to CESS evaluation.
It focuses on (1) the concrete contexts in which CESS takes place, (2) reflective
and dialogical learning processes, and (3) how to be democratic and inclusive. In
particular, this approach to CESS evaluation is akin to realist evaluation,
dialogical evaluation, and responsive evaluation. An example of a participatory
approach to evaluating CESS is presented and some critical issues concerning this
approach are discussed.
PMID- 28417518
TI - What Outcomes do Dutch Healthcare Professionals Perceive as Important Before
Participation in Moral Case Deliberation?
AB - BACKGROUND: There has been little attention paid to research on the outcomes of
clinical ethics support (CES) or critical reflection on what constitutes a good
CES outcome. Understanding how CES users perceive the importance of CES outcomes
can contribute to a better understanding, use of and normative reflection on CES
outcomes. OBJECTIVE: To describe the perceptions of Dutch healthcare
professionals on important outcomes of moral case deliberation (MCD), prior to
MCD participation, and to compare results between respondents. METHODS: This
mixed-methods study used both the Euro-MCD instrument and semi-structured
interviews. Healthcare professionals who were about to implement MCD were
recruited from nursing homes, hospitals, psychiatry and mentally disabled care
institutions. RESULTS: 331 healthcare professionals completed the Euro-MCD
instrument, 13 healthcare professionals were interviewed. The outcomes perceived
as most important were 'more open communication', 'better mutual understanding',
'concrete actions', 'see the situation from different perspectives', 'consensus
on how to manage the situation' and 'find more courses of action'. Interviewees
also perceived improving quality of care, professionalism and the organization as
important. Women, nurses, managers and professionals in mentally disabled care
rated outcomes more highly than other respondents. CONCLUSIONS: Dutch healthcare
professionals perceived the MCD outcomes related to collaboration as most
important. The empirical findings can contribute to shared ownership of MCD and a
more specific use of MCD in different contexts. They can inform international
comparative research on different CES types and contribute to normative
discussions concerning CES outcomes. Future studies should reflect upon important
MCD outcomes after having experienced MCD.
PMID- 28417519
TI - Methodological Reflections on the Contribution of Qualitative Research to the
Evaluation of Clinical Ethics Support Services.
AB - This article describes a process of developing, implementing and evaluating a
clinical ethics support service intervention with the goal of building up a
context-sensitive structure of minimal clinical-ethics in an oncology department
without prior clinical ethics structure. Scholars from different disciplines have
called for an improvement in the evaluation of clinical ethics support services
(CESS) for different reasons over several decades. However, while a lot has been
said about the concepts and methodological challenges of evaluating CESS up to
the present time, relatively few empirical studies have been carried out. The aim
of this article is twofold. On the one hand, it describes a process of
development, modifying and evaluating a CESS intervention as part of the ETHICO
research project, using the approach of qualitative-formative evaluation. On the
other hand, it provides a methodological analysis which specifies the
contribution of qualitative empirical methods to the (formative) evaluation of
CESS. We conclude with a consideration of the strengths and limitations of
qualitative evaluation research with regards to the evaluation and development of
context sensitive CESS. We further discuss our own approach in contrast to rather
traditional consult or committee models.
PMID- 28417520
TI - Integrating Theory and Data in Evaluating Clinical Ethics Support. Still a Long
Way to Go.
PMID- 28417521
TI - Evaluating the Quality of the Deliberation in Moral Case Deliberations: A Coding
Scheme.
AB - Moral Case Deliberation (MCD) is an up and coming form of ethics support wherein
clinical professionals deliberate about moral questions they face in their work.
So far, it has been unclear what quality of deliberation in MCD is entailed and
how to evaluate this quality. This article proposes a coding scheme that fits the
theoretical background of MCD and allows researchers to evaluate the quality of
the deliberation in MCDs. We consider deliberation in MCD to be of good quality
when participants enrich their own understanding of a case by being exposed to
the viewpoints of others. In order to have such an enriching effect, the
deliberation in an MCD ought to involve different kinds of arguments from the
perspectives of different stakeholders and in favour of different resolutions to
the case; and the process of deliberation ought to be critical but constructive.
PMID- 28417522
TI - Determinants of large drain losses early after pediatric liver transplantation.
AB - The goal of this study was to evaluate postoperative ascites to correlate it with
graft dysfunction and other complications. We therefore reviewed the files of
patients transplanted between 2009 and 2014 to correlate drain losses with
indication, patient and organ size, PELD, graft type, GRWR, NRBW, NGWD, cold
ischemia time, histologically proven graft dysfunction, and surgical
complications. Of 120 LTs in 104 patients, 48 (40%) were complicated by graft
dysfunction, 43 (36%) by surgical complications, and 25 (21%) by cellular
rejection. Large drain losses correlated with younger age (P=.05), graft
dysfunction (P<.01), surgical complications (P<.01), chylous ascites (P=.05);
there was no association with PELD, GRWR, NRBW, or NGWD. Graft dysfunction was
predicted by >20 mL/kg/d of ascites at age 0-2 years (AUROC 0.671), and >10
mL/kg/d above 2 years (AUROC 0.710). The measurement of drain losses after
pediatric LT could be used as a non-invasive marker of graft dysfunction. Younger
recipients tend to develop larger amounts of ascites, and its persistence is
associated with early complications.
PMID- 28417523
TI - Straightforward Synthesis of 2- and 2,8-Substituted Tetracenes.
AB - A simple regiospecific route to otherwise problematic substituted tetracenes is
described. The diverse cores (E)-1,2-Ar1 CH2 (HOCH2 )C=C(CH2 OH)I (Ar1 =Ph, 4
MePh, 4-MeOPh, 4-FPh) and (E)-1,2-I(HOCH2 )C=C(CH2 OH)I, accessed from ultra-low
cost HOCH2 C=CCH2 OH at multi-gram scales, allow the synthesis of diol libraries
(E)-1,2-Ar1 CH2 (HOCH2 )C=C(CH2 OH)CH2 Ar2 (Ar2 =Ph, 4-MePh, 4-iPrPh, 4-MeOPh, 4
FPh, 4-BrPh, 4-biphenyl, 4-styryl; 14 examples) by efficient Negishi coupling.
Copper-catalysed aerobic oxidation cleanly provides dialdehydes (E)-1,2-Ar1 CH2
(CHO)C=C(CHO)CH2 Ar2 , which in many cases undergo titanium(IV) chloride-induced
double Bradsher closure, providing a convenient method for the synthesis of
regiochemically and analytically pure tetracenes (12 examples). The sequence is
typically chromatography-free, scalable, efficient and technically simple to
carry out.
PMID- 28417524
TI - Biofilms of Candida spp. from the ocular conjunctiva of horses with reduced azole
susceptibility: a complicating factor for the treatment of keratomycosis?
AB - OBJECTIVES: This study aimed to assess the biofilm-forming ability of Candida
spp. from the ocular conjunctiva of horses and to investigate the antifungal
susceptibility of these biofilms. PROCEDURES: Initially, the biofilm-forming
ability of 15 strains was assessed by crystal violet staining, which reveals the
fungal biomass adhered to the polystyrene plates, and scanning electron
microscopy. Then, the minimum inhibitory concentrations (MICs) of amphotericin B,
fluconazole, itraconazole, and caspofungin were initially determined against
strains in planktonic form. Afterward, antifungal susceptibility of mature
biofilms was evaluated by exposing them to 10 * MIC and 50 * MIC of the tested
drugs, followed by the assessment of their metabolic activity, using the
oxidoreduction indicator XTT. Results were analyzed through ANOVA and Tukey's
post-test, and P-values below 5% led to significant conclusions. RESULTS: Eight
strains produced biofilms and were classified as strong (1/15), moderate (3/15)
and weak (4/15) producers, according to the amount of crystal violet retained by
the adhered fungal biomass. Biofilm metabolic activity of one C. tropicalis did
not decrease after exposure to the tested antifungals, while biofilm metabolic
activity of five strains was reduced by amphotericin B, but not the other drugs.
One C. parapsilosis sensu stricto and one C. glabrata showed significant
reduction in biofilm metabolic activity after exposure to fluconazole,
itraconazole, and caspofungin, but not amphotericin B. CONCLUSIONS: The results
demonstrate that Candida from the ocular conjunctiva of horses can pose as a risk
to animal health as they are capable of forming biofilms, which are commonly
involved in fungal keratitis.
PMID- 28417525
TI - Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm.
AB - Although metformin has been used for over 60 years, the balance between the
drug's beneficial and adverse effects is still subject to debate. Following an
analysis of how cases of so-called "metformin-associated lactic acidosis" (MALA)
are reported in the literature, the present article reviews the pitfalls to be
avoided when assessing the purported association between metformin and lactic
acidosis. By starting from pathophysiological considerations, we propose a new
paradigm for lactic acidosis in metformin-treated patients. Metformin therapy
does not necessarily induce metformin accumulation, just as metformin
accumulation does not necessarily induce hyperlactatemia, and hyperlactatemia
does not necessarily induce lactic acidosis. In contrast to the conventional
view, MALA probably accounts for a smaller proportion of cases than either
metformin-unrelated lactic acidosis or metformin-induced lactic acidosis. Lastly,
this review highlights the need for substantial improvements in the reporting of
cases of lactic acidosis in metformin-treated patients. Accordingly, we propose a
check-list as a guide to clinical practice.
PMID- 28417526
TI - Response to letter to editor titled "Para-Hisian Pacing Maneuver: A Pitfall in
the Pitfall".
PMID- 28417527
TI - Effects of dapagliflozin on insulin-requirement, glucose excretion and beta
hydroxybutyrate levels are not related to baseline HbA1c in youth with type 1
diabetes.
AB - Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore,
this placebo-controlled, randomized, crossover study was set up to assess the
safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin
(DAPA) as add-on to insulin in relationship to HbA1c in youth. A total of 33
youths (14 males, median age 16 years, diabetes duration 8 years) were included
and stratified into 3 baseline HbA1c categories (<7.5%, 7.5%-9.0% or >9.0; n = 11
each). During the study period of 24 hours, intravenous insulin administration
and glucose-infusion kept blood glucose levels at 160 to 220 mg/dL. DAPA reduced
mean insulin dose by 13.6% ( P < .0001 by ANOVA) and increased urinary glucose
excretion by 610% (143.4 vs 22.4 g/24 h; P < .0001), both irrespective of
baseline HbA1c. Six independent episodes in 6 patients with plasma beta
hydroxybutyrate levels between >=0.6 and <1.0 mmol/L were observed after liquid
meal challenges, 5 episodes in the DAPA group and 1 in the placebo group. This
study provides a proof-of-concept, irrespective of preexisting HbA1c levels, for
adjunct SGLT2-inhibitor therapy in the paediatric age group by lowering insulin
dose and increasing glucose excretion.
PMID- 28417528
TI - Attribution of seasonal leaf area index trends in the northern latitudes with
"optimally" integrated ecosystem models.
AB - Significant increases in remotely sensed vegetation indices in the northern
latitudes since the 1980s have been detected and attributed at annual and growing
season scales. However, we presently lack a systematic understanding of how
vegetation responds to asymmetric seasonal environmental changes. In this study,
we first investigated trends in the seasonal mean leaf area index (LAI) at
northern latitudes (north of 30 degrees N) between 1982 and 2009 using three
remotely sensed long-term LAI data sets. The most significant LAI increases
occurred in summer (0.009 m2 m-2 year-1 , p < .01), followed by autumn (0.005
m2 m-2 year-1 , p < .01) and spring (0.003 m2 m-2 year-1 , p < .01). We then
quantified the contribution of elevating atmospheric CO2 concentration (eCO2 ),
climate change, nitrogen deposition, and land cover change to seasonal LAI
increases based on factorial simulations from 10 state-of-the-art ecosystem
models. Unlike previous studies that used multimodel ensemble mean (MME), we used
the Bayesian model averaging (BMA) to optimize the integration of model ensemble.
The optimally integrated ensemble LAI changes are significantly closer to the
observed seasonal LAI changes than the traditional MME results. The BMA factorial
simulations suggest that eCO2 provides the greatest contribution to increasing
LAI trends in all seasons (0.003-0.007 m2 m-2 year-1 ), and is the main factor
driving asymmetric seasonal LAI trends. Climate change controls the spatial
pattern of seasonal LAI trends and dominates the increase in seasonal LAI in the
northern high latitudes. The effects of nitrogen deposition and land use change
are relatively small in all seasons (around 0.0002 m2 m-2 year-1 and 0.0001
0.001 m2 m-2 year-1 , respectively). Our analysis of the seasonal LAI responses
to the interactions between seasonal changes in environmental factors offers a
new perspective on the response of global vegetation to environmental changes.
PMID- 28417529
TI - Cardiovascular risk management in rheumatoid arthritis: A large gap to close.
AB - OBJECTIVE: Rheumatoid arthritis (RA) portends significant cardiovascular
morbidity and mortality. We therefore determined how often rheumatologists
screened for and managed cardiovascular risk factors in RA patients, and the
barriers to doing so. METHODS: We examined 300 patient charts from 10 university
affiliated rheumatology practices, to ascertain if they had been screened,
treated and/or referred over a 3-year period. We subsequently distributed a
national survey to Canadian rheumatologists to elucidate challenges in performing
optimal cardiovascular risk modification. RESULTS: Most patients were screened
for hypertension. Forty-one per cent were found to be hypertensive; however, the
majority of these patients were neither treated nor referred to another provider
for management. A small minority of patients were screened for diabetes and/or
hyperlipidaemia, and these were usually not addressed if abnormal. Men were
referred more frequently than women. Consistent with these findings, the majority
of rheumatologists from the national survey felt that they did not manage
cardiovascular risk adequately; 79.4% cited a lack of time as a major barrier,
and 82.5% felt that it should be managed by the primary care provider.
CONCLUSION: There is marked underdiagnosis and undertreatment of cardiac risk in
RA. Several major barriers exist, including lack of time. Most rheumatologists
feel that this aspect of care is the responsibility of primary care physicians.
PMID- 28417531
TI - Desmoid-type fibromatosis in a boy with Down syndrome.
AB - Patients with Down syndrome (DS) have a markedly higher incidence of childhood
leukemia, but a lower incidence of most solid tumors, compared with age-matched
euploid individuals. Trisomy 21 might be protective against tumorigenesis because
of several tumor suppressive mechanisms. Desmoid-type fibromatosis (DF) is a rare
monoclonal, fibroblastic proliferation characterized by a variable clinical
course. In recent reports, almost all cases of DF involved genomic alterations
associated with activation of the Wnt/beta-catenin pathway. Here, we report the
case of a boy with DS who developed DF without activation of the Wnt/beta-catenin
pathway. To the best of our knowledge, this is the first case of DS involving DF.
PMID- 28417530
TI - Rho GDP-dissociation inhibitor alpha is a potential prognostic biomarker and
controls telomere regulation in colorectal cancer.
AB - Rho GDP-dissociation inhibitor alpha (RhoGDIalpha) is an essential regulator for
Rho GTPases. Although RhoGDIalpha may serve as an oncogene in colorectal cancer
(CRC), the underlying mechanism is still unclear. We investigated the function,
mechanism, and clinical significance of RhoGDIalpha in CRC progression. We
founded that downregulation of RhoGDIalpha repressed CRC cell proliferation,
motility, and invasion. Overexpression of RhoGDIalpha increased DNA damage
response signals at telomeres, and led to telomere shortening in CRC cells, also
being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that
RhoGDIalpha could promote telomeric repeat factor 1 (TRF1) expression through the
phosphatidylinositol 3-kinase-protein kinase B signal pathway. Moreover,
RhoGDIalpha protein levels were strongly correlated with TRF1 in CRC tissues. A
cohort of 297 CRC samples validated the positive relationship between RhoGDIalpha
and TRF1, and revealed that RhoGDIalpha and TRF1 levels were negatively
associated with CRC patients' survival. Taken together, our results suggest that
RhoGDIalpha regulate TRF1 and telomere length and may be novel prognostic
biomarkers in colorectal cancer.
PMID- 28417532
TI - Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic
associations in patients with type 1 diabetes and type 2 diabetes.
AB - We investigated non-alcoholic fatty liver disease (NAFLD) prevalence and its
metabolic associations in patients with type 1 diabetes (T1D), and in insulin
naive and insulin-treated patients with type 2 diabetes (T2D). Baseline data from
patients who had liver fat content (LFC) evaluated by magnetic resonance imaging
in four phase 3 studies of basal insulin peglispro (BIL) were analysed.
Associations of NAFLD with clinical characteristics, glycaemic control and
diabetes therapy were evaluated. The prevalence of NAFLD (defined as LFC >= 6%)
was low in T1D (8.8%) but high in T2D, with greater prevalence in insulin-naive
(75.6%) vs insulin-treated (61.7%) T2D patients. LFC (mean +/- SD) was higher in
T2D patients (insulin-naive, 13.0% +/- 8.4%; insulin-treated, 10.2% +/- 7.8%)
than in T1D patients (3.2% +/- 3.2%). In T2D, NAFLD was associated with several
markers of insulin resistance. In all three populations, there was an absence of
association of HbA1c with LFC, but insulin doses were higher in patients with
NAFLD.
PMID- 28417533
TI - Split tasks of asymmetric nucleotide-binding sites in the heterodimeric ABC
exporter EfrCD.
AB - Many heterodimeric ATP-binding cassette (ABC) exporters evolved asymmetric ATP
binding sites containing a degenerate site incapable of ATP hydrolysis due to
noncanonical substitutions in conserved sequence motifs. Recent studies revealed
that nucleotide binding to the degenerate site stabilizes contacts between the
nucleotide-binding domains (NBDs) of the inward-facing transporter and regulates
ATP hydrolysis at the consensus site via allosteric coupling mediated by the D
loops. However, it is unclear whether nucleotide binding to the degenerate site
is strictly required for substrate transport. In this study, we examined the
functional consequences of a systematic set of mutations introduced at the
degenerate and consensus site of the multidrug efflux pump EfrCD of Enterococcus
faecalis. Mutating motifs which differ among the two ATP-binding sites (Walker B,
switch loop, and ABC signature) or which are involved in interdomain
communication (D-loop and Q-loop) led to asymmetric results in the functional
assays and were better tolerated at the degenerate site. This highlights the
importance of the degenerate site to allosterically regulate the events at the
consensus site. Mutating invariant motifs involved in ATP binding and NBD closure
(A-loop and Walker A) resulted in equally reduced transport activities,
regardless at which ATP-binding site they were introduced. In contrast to
previously investigated heterodimeric ABC exporters, mutation of the degenerate
site Walker A lysine completely inactivated ATPase activity and substrate
transport, indicating that ATP binding to the degenerate site is essential for
EfrCD. This study provides novel insights into the split tasks of asymmetric ATP
binding sites of heterodimeric ABC exporters.
PMID- 28417534
TI - Cardiac function and cognition in older community-dwelling cardiac patients.
AB - BACKGROUND: Cognitive deficits have been reported in older cardiac patients. An
underlying mechanism for these findings may be reduced cardiac function. The
relationship between cardiac function as represented by different
echocardiographic measures and different cognitive function domains in older
cardiac patients remains unknown. METHODS: An older (>=70 years) heterogeneous
group of 117 community-dwelling cardiac patients under medical supervision by a
cardiologist underwent thorough echocardiographic assessment including left
ventricular ejection fraction, cardiac index, left atrial volume index, left
ventricular mass index, left ventricular diastolic function, and valvular
calcification. During a home visit, a neuropsychological assessment was performed
within 7.1 +/- 3.8 months after echocardiographic assessment; the
neuropsychological assessment included three subtests of a word-learning test
(encoding, recall, recognition) to examine one memory function domain and three
executive function tests, including digit span backwards, Trail Making Test B
minus A, and the Stroop colour-word test. RESULTS: Regression analyses showed no
significant linear or quadratic associations between any of the echocardiographic
functions and the cognitive function measures. CONCLUSIONS: None of the
echocardiographic measures as representative of cardiac function was correlated
with memory or executive function in this group of community-dwelling older
cardiac patients. These findings contrast with those of previous studies.
PMID- 28417536
TI - Stretchable and Soft Electronics using Liquid Metals.
AB - The use of liquid metals based on gallium for soft and stretchable electronics is
discussed. This emerging class of electronics is motivated, in part, by the new
opportunities that arise from devices that have mechanical properties similar to
those encountered in the human experience, such as skin, tissue, textiles, and
clothing. These types of electronics (e.g., wearable or implantable electronics,
sensors for soft robotics, e-skin) must operate during deformation. Liquid metals
are compelling materials for these applications because, in principle, they are
infinitely deformable while retaining metallic conductivity. Liquid metals have
been used for stretchable wires and interconnects, reconfigurable antennas, soft
sensors, self-healing circuits, and conformal electrodes. In contrast to Hg,
liquid metals based on gallium have low toxicity and essentially no vapor
pressure and are therefore considered safe to handle. Whereas most liquids bead
up to minimize surface energy, the presence of a surface oxide on these metals
makes it possible to pattern them into useful shapes using a variety of
techniques, including fluidic injection and 3D printing. In addition to forming
excellent conductors, these metals can be used actively to form memory devices,
sensors, and diodes that are completely built from soft materials. The properties
of these materials, their applications within soft and stretchable electronics,
and future opportunities and challenges are considered.
PMID- 28417535
TI - Rates of hypoglycaemia are lower in patients treated with insulin
degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of
the hypoglycaemia definition used.
AB - AIMS: To re-analyse, using a series of alternative hypoglycaemia definitions, the
data from 2 trials, DUAL I and V, in which the once-daily, fixed ratio
combination of insulin degludec/liraglutide (IDegLira) was compared with basal
insulin therapy. MATERIAL AND METHODS: Post hoc analyses of the DUAL I (patients
uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on
insulin glargine (IGlar) U100) trials were carried out using different
definitions of hypoglycaemia and according to whether treatments were
administered in the morning or afternoon. Rates of hypoglycaemia for the
definitions of confirmed and American Diabetes Association (ADA)-documented
symptomatic hypoglycaemia were compared according to age, gender and body mass
index (BMI). RESULTS: Although hypoglycaemia rates differed according to the
alternative hypoglycaemia definitions, rates were consistently lower with
IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin
concentrations being lower with IDegLira at end of treatment, confirmed and
nocturnal-confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar
U100, irrespective of dosing time. The definitions of confirmed and ADA
documented symptomatic hypoglycaemia did not have a significant effect on the
treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when
further assessed by baseline age, gender and BMI. CONCLUSIONS: Treatment with
IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia
regardless of dosing time and definition of hypoglycaemia used. The choice of
hypoglycaemia definition did not influence the results of analyses when
stratified by age, sex and BMI.
PMID- 28417537
TI - The effects and mechanism of action of methane on ileal motor function.
AB - BACKGROUND: Methane has been associated with constipation-predominant irritable
bowel syndrome, slowing intestinal transit time by augmenting contractile
activity. However, the precise mechanism underlying this effect remains unclear.
Therefore, we investigated the mechanisms underlying the effect of methane on
contractile activity, and whether such effects are mediated by nerve impulses or
muscular contraction. METHODS: We connected guinea pig ileal muscle strips to a
force/tension transducer and measured amplitudes of contraction in response to
electrical field stimulation (EFS; 1, 2, 8, 16 Hz) following methane infusion in
the presence of tetradotoxin (TTX), atropine, guanethidine, or GR 113808. We then
performed calcium imaging using Oregon Green 488 BAPTA-1 AM in order to visualize
changes in calcium fluorescence in response to EFS following methane infusion in
the presence of TTX, atropine, or a high K+ solution. KEY RESULTS: Methane
significantly increased amplitudes of contraction (P<.05), while treatment with
TTX abolished such contraction. Methane-induced increases in amplitude were
inhibited when lower-frequency (1, 2 Hz) EFS was applied following atropine
infusion (P<.05). Neither guanethidine nor GR 113808 significantly altered
contraction amplitudes. Methane significantly increased calcium fluorescence,
while this increase was attenuated following atropine infusion (P<.05). Although
calcium fluorescence was increased by the high K+ solution under pretreatment
with TTX, the intensity of fluorescence remained unchanged after methane
infusion. CONCLUSIONS AND INFERENCES: The actions of methane on the intestine are
influenced by the cholinergic pathway of the enteric nervous system. Our findings
support the classification of methane as a gasotransmitter.
PMID- 28417538
TI - Synthesis of Long Oxahelicenes by Polycyclization in a Flow Reactor.
AB - A series of oxahelicenes composed of ortho/meta-annulated benzene/pyridine and 2H
pyran rings were synthesized on the basis of the cobalt(I)-mediated (or
rhodium(I)- or nickel(0)-mediated) double, triple, or quadruple [2+2+2]
cycloisomerization of branched aromatic hexa-, nona-, or dodecaynes, thus
allowing the construction of 6, 9, or 12 rings in a single operation. The use of
a flow reactor was found to be beneficial for the multicyclization reactions. The
stereogenic centers present in some of the oligoynes steered the helical folding
in such a way that the final oxa[9]-, [13]-, [17]- and [19]helicenes were
obtained in both enantiomerically and diastereomerically pure form. Specifically,
the oxa[19]helicenes beat the current record in the length of a helicene
backbone. Single-molecule conductivity was studied by the mechanically
controllable break-junction method with a pyridooxa[9]helicene.
PMID- 28417540
TI - Medium-chain triglycerides given in the early stage of mild-to-moderate
Alzheimer's disease enhance memory function.
PMID- 28417539
TI - USP22 mediates the multidrug resistance of hepatocellular carcinoma via the
SIRT1/AKT/MRP1 signaling pathway.
AB - Drug treatments for hepatocellular carcinoma (HCC) often fail because of
multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem
cells (CSCs), which are able to self-renew and differentiate, have recently been
shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22
(USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in
MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we
found that modified USP22 levels were responsible for the altered drug-resistant
phenotype of BEL7402 and BEL/FU cells. Downregulation of USP22 dramatically
inhibited the expression of ABCC1 (encoding MRP1) but weakly influenced ABCB1
(encoding P-glycoprotein). Sirtuin 1 (SIRT1) was reported previously as a
functional mediator of USP22 that could promote HCC cell proliferation and
enhance resistance to chemotherapy. In this study, USP22 directly interacted with
SIRT1 and positively regulated SIRT1 protein expression. Regulation of the
expression of both USP22 and SIRT1 markedly affected the AKT pathway and MRP1
expression. Inhibition of the AKT pathway by its specific inhibitor LY294002
resulted in downregulation of MRP1. USP22 and MRP1 expression was detected in 168
clinical HCC samples by immunohistochemical staining, and a firm relationship
between USP22 and MRP1 was identified. Together, these results indicate that
USP22 could promote the MDR in HCC cells by activating the SIRT1/AKT/MRP1
pathway. USP22 might be a potential target, through which the MDR of HCC in
clinical setting could be reversed.
PMID- 28417541
TI - Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal
cell carcinoma.
AB - Advanced-stage renal cell carcinoma (RCC) carries a dismal prognosis for
pediatric patients with few studied therapeutic options. Cabozantinib is a small
molecule tyrosine kinase inhibitor against the oncoprotein MET. It is currently
approved by the U.S. Food and Drug administration for second-line treatment of
RCC in adults. There is no published data on its use in children with RCC. We
report here two pediatric patients with recurrent metastatic RCC whose tumors
expressed MET and were treated with cabozantinib. Both patients had significant
disease regression and symptomatic improvement for over 15 months with tolerable
adverse effects. Cabozantinib can maintain prolonged disease control in pediatric
RCC and warrants further study.
PMID- 28417542
TI - Vertically Oriented Graphene Nanoribbon Fibers for High-Volumetric Energy Density
All-Solid-State Asymmetric Supercapacitors.
AB - Graphene fiber based micro-supercapacitors (GF micro-SCs) have attracted great
attention for their potential applications in portable and wearable electronics.
However, due to strong pi-pi stacking of nanosheets for graphene fibers, the
limited ion accessible surface area and slow ion diffusion rate leads to low
specific capacitance and poor rate performance. Here, the authors report a
strategy for the synthesis of a vertically oriented graphene nanoribbon fiber
with highly exposed surface area through confined-hydrothermal treatment of
interconnected graphene oxide nanoribbons and consequent laser irradiation
process. As a result, the as-obtained fiber shows high length specific
capacitance of 3.2 mF cm-1 and volumetric capacitance of 234.8 F cm-3 at 2 mV s-1
, as well as excellent rate capability and outstanding cycling performance (96%
capacitance retention after 10 000 cycles). Moreover, an all-solid-state
asymmetric supercapacitor based on graphene nanoribbon fiber as negative
electrode and MnO2 coated graphene ribbon fiber as positive electrode, shows high
volumetric capacitance and energy density of 12.8 F cm-3 and 5.7 mWh cm-3
(normalized to the device volume), respectively, much higher than those of
previously reported GF micro-SCs, as well as a long cycle life with 88% of
capacitance retention after 10 000 cycles.
PMID- 28417543
TI - Efficiency of Cathodoluminescence Emission by Nitrogen-Vacancy Color Centers in
Nanodiamonds.
AB - Correlated electron microscopy and cathodoluminescence (CL) imaging using
functionalized nanoparticles is a promising nanoscale probe of biological
structure and function. Nanodiamonds (NDs) that contain CL-emitting color centers
are particularly well suited for such applications. The intensity of CL emission
from NDs is determined by a combination of factors, including particle size,
density of color centers, efficiency of energy deposition by electrons passing
through the particle, and conversion efficiency from deposited energy to CL
emission. This paper reports experiments and numerical simulations that
investigate the relative importance of each of these factors in determining CL
emission intensity from NDs containing nitrogen-vacancy (NV) color centers. In
particular, it is found that CL can be detected from NV-doped NDs with dimensions
as small as ~40 nm, although CL emission decreases significantly for smaller NDs.
PMID- 28417544
TI - Urine biomarkers of acute kidney injury in noncritically ill, hospitalized
children treated with chemotherapy.
AB - BACKGROUND: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common
nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early
acute kidney injury (AKI) diagnosis. PROCEDURE: We performed a two-center
(Canada, United States) pilot study to prospectively measure serum creatinine
(SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin
18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and
in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney
Disease Improving Global Outcomes (KDIGO) definition. We compared
postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3
days later) to pre-infusion concentrations. We calculated area under the receiver
operating characteristic curve (AUC) for postinfusion biomarkers to discriminate
for AKI. RESULTS: Prechemotherapy infusion NGAL and IL-18 concentrations were not
higher than nonchemotherapy control concentrations. Increasing chemotherapy dose
was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P <
0.05). Post-Ifos, immediate postdose, and daily postdose NGAL and IL-18 were
significantly higher than pre-infusion biomarker concentrations (P < 0.05),
during AKI episodes. NGAL and IL-18 did not rise significantly after Cis-Carb
infusion, relative to predose concentrations (P > 0.05). NGAL and IL-18 measured
immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard
error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were
not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all
biomarker AUCs (Cis-Carb and Ifos) improved. CONCLUSION: Urine NGAL and IL-18
show promise as early AKI diagnostic tests in children treated with ifosfamide
and may have a potential role in drug toxicity monitoring.
PMID- 28417545
TI - Gender composition of the occupation, sexual orientation, and mental health in
young adulthood.
AB - The gender composition of the occupation has important implications for work
conditions, rewards, and experiences, but little is known about whether it
impacts workers' mental health. The present study seeks to answer this question
by focusing on depressive symptoms and drug dependence symptoms as mental health
outcomes and young adulthood as the life course context. The study further
examines whether the association varies by sexual orientation, considering that
occupational gender composition affects levels of stress exposure and social
support availability in different ways for heterosexuals and sexual minorities.
The analysis of the U.S. data, the National Longitudinal Study of Adolescent to
Adult Health (Add Health), shows that among heterosexuals, working in a more
female-typical occupation is associated with lower levels of drug dependence
symptoms for women and higher levels of depressive symptoms for men. Sexual
minorities show a diverging pattern-working in a more female-typical occupation
is associated with worse mental health for sexual minority women and better
mental health for sexual minority men.
PMID- 28417546
TI - Novel Structure for High Performance UV Photodetector Based on BiOCl/ZnO Hybrid
Film.
AB - A novel type of high performance ultraviolet (UV) photodetector (PD) based on a
ZnO film has been prepared by incorporating a BiOCl nanostructure into the film.
The responsivity of the BiOCl/ZnO hybrid film PD in UV region can reach 182.87 mA
W-1 , which is about 2.72 and 6.87 times for that of TiO2 /ZnO hybrid film PD and
pure ZnO film PD. The rise/decay time of BiOCl/ZnO hybrid film PD is 25.83/11.25
s, which is much shorter than that of TiO2 /ZnO hybrid film PD (51.94/26.05 s)
and pure ZnO film PD (69.34/>120 s). The BiOCl nanostructure can inject
photogenerated electrons into the ZnO film under UV light illumination, leading
to the increase of photocurrent, and forms barriers to block the straight
transmission of electrons between electrodes, resulting in the decrease of decay
time. The results of control experiment show that the transfer path of
photogenerated electrons formed by p-n junction will be cut off after depositing
gold nanoparticles on the film surface, which means this hybrid film is a unique
and novel structure to improve the optoelectronic performance of photodetectors.
This novel BiOCl/ZnO hybrid structure paves new route for the development of film
PDs based on ZnO film.
PMID- 28417547
TI - A long-term follow-up study of subtotal splenectomy in children with hereditary
spherocytosis.
AB - BACKGROUND: Hereditary spherocytosis (HS) is a heterogeneous hemolytic anemia
treated with splenectomy in patients suffering from severe or moderate disease.
Total splenectomy, however, renders patients vulnerable to overwhelming
postsplenectomy infection despite preventive measures. Although subtotal
splenectomy has been advocated as an alternative to total splenectomy, long-term
follow-up data are scarce. We investigated how often hematologic recurrences
requiring secondary total splenectomy occurred. PROCEDURE: With a follow-up of at
least 5 years, we analyzed the data of 12 patients, aged 11 years maximum (median
6.5 years), who had undergone intended subtotal splenectomy, and 9 patients
(median age 11.9 years), who had undergone total splenectomy. We compared their
hematologic results and searched for factors associated with secondary spleen
surgery. RESULTS: Hemolysis was reduced after subtotal splenectomy and absent
after total splenectomy. Subtotal splenectomy was not successful in three
children because no functional splenic remnant remained after 6 months (one
conversion at surgery; one necrosis of splenic remnant; one early secondary
splenectomy). Four children required secondary splenectomy after a median of 5
years for hematologic recurrence. In the remaining five patients, a functional
splenic remnant was present for at least 5.5 years. The median time to secondary
total splenectomy after intended subtotal splenectomy was 5.2 years. In all
patients requiring secondary total splenectomy, increased reticulocyte levels
within 2 years indicated hematologic recurrence. CONCLUSIONS: Subtotal
splenectomy can be an alternative for total splenectomy in young patients with
HS. It allows for hematologic improvement and may preserve splenic immune
function for as many as 5 years.
PMID- 28417548
TI - Resistive Switching Performance Improvement via Modulating Nanoscale Conductive
Filament, Involving the Application of Two-Dimensional Layered Materials.
AB - Reversible chemical and structural changes induced by ionic motion and reaction
in response to electrical stimuli leads to resistive switching effects in metal
insulator-metal structures. Filamentary switching based on the formation and
rupture of nanoscale conductive filament has been applied in non-volatile memory
and volatile selector devices with low power consumption and fast switching
speeds. Before the mass production of resistive switching devices, great efforts
are still required to enable stable and reliable switching performances. The
conductive filament, a bridge of microscopic metal-insulator-metal structure and
macroscopic resistance states, plays an irreplaceable part in resistive switching
behavior, as unreliable performance often originates from unstable filament
behavior. In this Review, departing from the filamentary switching mechanism and
the existing issues, recent advances of the switching performance improvement
through the conductive filament modulation are discussed, in the sequence of
material modulation, device structure design and switching operation scheme
optimization. In particular, two-dimensional (2D) nanomaterials with excellent
properties including and beyond graphene, are discussed with emphasis on
performance improvement by their active roles as the switching layer, insertion
layer, thin electrode, patterned electrode, and edge electrode, etc.
PMID- 28417549
TI - Searching for a job: Cardiac responses to acute stress and the mediating role of
threat appraisal in young people.
AB - Being unemployed and looking for a job has become a source of stress for many
people in several European countries. However, little attention has been paid to
the impact of this stressful situation on the individuals' psychophysiological
stress responses. The aim of this study was to investigate the effect of being an
unemployed job seeker on cognitive threat appraisal and cardiac responses to a
psychosocial stressor. We exposed a group of unemployed job seekers (N = 42) and
a matched group of unemployed non-job seekers (N = 40) to a standardized social
stressor in form of job interview, the Trier Social Stress Test. Our results
showed that unemployed job seekers manifest lower cardiac responses, along with a
lower cognitive threat appraisal, compared to non-job seekers. Moreover, we
observed a full mediating role of cognitive threat appraisal on the relationship
between being an unemployed job seeker and cardiac responses to stress. These
findings reveal that being unemployed and looking for a job has an effect on
physiological responses to acute stress, as well as the importance of
psychological process related to the situation. These responses might lead to
negative health and motivational consequences. Theoretical and practical
implications are discussed.
PMID- 28417550
TI - Burden, emotional distress and quality of life among informal caregivers of lung
cancer patients: An exploratory study.
AB - This study was conducted to explore the interrelationships among caregiver
burden, emotional status and quality of life (QoL) in caregivers of lung cancer
patients, and to identify whether caregiver burden and health status are
associated with patient emotional status and QoL. Forty-three dyads of lung
cancer patients and their caregivers were included for analysis. Caregiver
reported outcomes were measured by Caregiver Burden Scale (CBS), Caregivers
Quality of Life Index-Cancer (CQOLC) and Hospital Anxiety and Depression Scale
(HADS), while patient-reported outcomes were collected by HADS and Lung Cancer
Symptom Scale (LCSS). The majority of the CBS and CQOLC scores were significantly
higher in anxious and depressed caregivers than non-anxious and non-depressed
caregivers (p < .01 or .05). Caregivers of depressed patients experienced
significantly greater emotional distress than those of non-depressed patients (p
< .01). Significantly positive associations were identified among most of the
CBS, CQOLC and caregiver HADS scores. Patient LCSS scores were positively
correlated with the CBS and caregiver HADS scores, and patient HADS scores were
also positively related to caregiver HADS scores. The close interrelationships
between caregiver and patient health outcomes provide evidence that lung cancer
patients and their caregivers should be viewed as a unit in future supportive
service models.
PMID- 28417551
TI - Morbidity and mortality after treatment of Ewing sarcoma: A single-institution
experience.
AB - BACKGROUND: Children, adolescents, and young adults treated for Ewing sarcoma
(ES) are at risk for disease-related and treatment-related complications. We
aimed to describe early and late overall mortality, cause-specific mortality, and
key adverse health outcomes in a large, single-institutional cohort of patients
with ES. METHODS: Patients with ES diagnosed at age less than 40 years and
treated at Memorial Sloan Kettering between 1974 and 2012 were included. Overall
survival was estimated using Kaplan-Meier methods. Cox proportional hazards were
used to examine the association of clinical and pathologic variables with overall
survival. Cause-specific mortality was evaluated with the cumulative incidence
function accounting for competing risks. RESULTS: Three hundred patients with ES
(60.3% male; median age at diagnosis: 16.8 years [range: 0.3-39]; 30.0% with
metastatic disease at diagnosis) were followed for a median of 7.8 years (range:
0.2-37). Five-year overall survival was 65.2% (95% confidence interval [95% CI],
59.8-71.1%) for the entire cohort; 78.6% for those with localized disease; 40.1%
for those with isolated pulmonary metastases; and 28.1% for those with
extrapulmonary metastases. In multivariable analysis, older age at diagnosis,
minority race/ethnicity, and metastatic disease at diagnosis were associated with
inferior survival. Ten-year cumulative incidence of relapse/progression was
40.1%, with eight late relapses occurring at a median of 6.3 years after
diagnosis (range: 5-14). Seventeen patients developed subsequent neoplasms
(treatment-related myelodysplastic syndrome/acute myelogenous leukemia = 9; solid
tumors = 6; nonmelanoma skin cancer [NMSC] = 4). Excluding NMSC and melanoma in
situ, the cumulative incidence of subsequent malignant neoplasms at 25 years was
15% (95% CI, 4.8-25.1%). CONCLUSION: Patients with ES are at high risk for
relapse/progression and second cancers.
PMID- 28417552
TI - Enhanced phototoxicity of photodynamic treatment by Cx26-composed GJIC via ROS-,
calcium- and lipid peroxide-mediated pathways.
AB - In spite of the promising initial treatment responses presented by photodynamic
therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement
in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26
composed gap junctional intercellular communication (GJIC) enhances the
intercellular propagation of "death signal", thereby increasing chemotherapeutic
cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on
PDT phototoxicity. The results in the present study showed that Cx26-composed GJ
formation at high density enhances the phototoxicity of Photofrin-PDT. When the
Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high
density cultures substantially reduces, indicating that the enhanced PDT
phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC
mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid
peroxide-mediated stress signaling pathways. The work presents the ability of
Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and
indicates that maintenance or increase of Cx26-formed GJIC may be a profitable
strategy towards the enhancement of PDT therapeutic efficiency. Picture: The
survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed)
and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density
condition.
PMID- 28417553
TI - Calcineurin inhibitor-free strategies for prophylaxis and treatment of GVHD in
children with posterior reversible encephalopathy syndrome after stem cell
transplantation.
AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a distinct
clinico-radiologic entity that can occur following allogeneic hematopoietic stem
cell transplantation, often in the context of treatment with calcineurin
inhibitors (CNIs). PROCEDURE: We describe the results of CNI-free management of
14 children with PRES and review the clinical and radiologic manifestations of
their presentation. RESULTS: Discontinuation of CNIs usually resulted in
remission of PRES, but patients with established graft versus host disease (GVHD)
at the time when treatment was changed often experienced progressive GVHD despite
administration of immune suppressive and modulating treatments. All but three
patients experienced full neurologic recovery. Nine children died as a result of
either GVHD, disease relapse, or severe infection. CONCLUSIONS: Discontinuation
of CNIs results in neurologic improvement in most cases, but superior alternative
immune modulatory treatment is needed to prevent progression of established GVHD.
PMID- 28417555
TI - A Novel Bat-Shaped Dicyanomethylene-4H-pyran-Functionalized Naphthalimide for
Highly Efficient Solution-Processed Multilevel Memory Devices.
AB - Small-molecule-based multilevel memory devices have attracted increasing
attention because of their advantages, such as super-high storage density, fast
reading speed, light weight, low energy consumption, and shock resistance.
However, the fabrication of small-molecule-based devices always requires
expensive vacuum-deposition techniques or high temperatures for spin-coating.
Herein, through rational tailoring of a previous molecule, DPCNCANA (4,4'-(6,6'
bis(2-octyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-9H,9'H-[3,3'
bicarbazole]-9,9'-diyl)dibenzonitrile), a novel bat-shaped A-D-A-type (A-D
A=acceptor-donor-acceptor) symmetric framework has been successfully synthesized
and can be dissolved in common solvents at room temperature. Additionally, it has
a low-energy bandgap and dense intramolecular stacking in the film state. The
solution-processed memory devices exhibited high-performance nonvolatile
multilevel data-storage properties with low switching threshold voltages of about
-1.3 and -2.7 V, which is beneficial for low power consumption. Our result should
prompt the study of highly efficient solution-processed multilevel memory devices
in the field of organic electronics.
PMID- 28417556
TI - An HLA-B7-specific antibody in an HLA-B*07 positive patient explained by a
nonexpressed allele (HLA-B*07:181N).
AB - Antibody identification by a bead array assay in a kidney patient revealed
several HLA-specific antibodies including one directed against the HLA-B7
antigen. Low-resolution typing of the patient indicated the presence of an HLA
B*07 allele. To rule out an HLA-specific autoantibody the HLA-typing of the
patient was further refined by nucleotide sequencing on a next-generation
sequencing platform and eventually showed an HLA-B*39:01:01:03 and HLA-B*07:181N
genotype. Thereby the allospecific nature of the antibody was proven. The HLA-B7
specific antibody could be explained by an immunization during the first kidney
transplantation in 1996 with an HLA-B*07 positive donor. When assessing the
plausibility of antibodies, the presence of nonexpressed alleles should be taken
into consideration.
PMID- 28417558
TI - The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related
traits and mediates by interacting with Apo-A1.
AB - OBJECTIVE: Despite alarming obesity levels in the Arabian Peninsula, its
population lacks convincingly identified genetic determinants of obesity. A
genome-wide association study was performed for obesity-related anthropometric
traits in Arabs and to decipher mechanisms by which the variants mediate traits.
METHODS: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab
individuals (largely with Class I obesity) from Kuwait. Genome-wide association
tests for obesity-related anthropometric traits were performed. Top associations
were tested for replication in an independent cohort (1,176 unrelated Arabs).
Resultant variants were investigated for interactions with obesity-related plasma
biomarkers. Pathway analysis was performed on genes harboring markers in linkage
disequilibrium (LD) with identified variants. RESULTS: The
rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist
circumference (WC) at nearly genome-wide significance (P = 8.92E-08). WC was
inversely related with Apo-A1 or high-density lipoprotein levels; individuals
with the AG genotype exhibited stronger relationship than those with the
reference AA genotype. Interaction involving the AG genotype (effect allele = G)
significantly contributed to an increase in anthropometric traits (particularly
WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped
onto an interaction network (with TP53 as central element) of established
obesity/diabetes-related protein components. CONCLUSIONS: The TCN2 variant acts
as a risk factor for WC in the Arab population. The variant mediates obesity
related anthropometric traits via interactions with Apo-A1/high-density
lipoprotein or TP53.
PMID- 28417557
TI - A Multitarget Approach toward the Development of 8-Substituted Purines for
Photoprotection and Prevention of UV-Related Damage.
AB - Ultraviolet (UV) light is the most abundant and significant modifiable risk
factor for skin cancer and many other skin diseases such as early photo-aging.
Across the solar radiation spectrum, UV light is the main cause behind skin
problems. In the search for novel photoprotective compounds, a new series of 8
substituted purines were synthesized from commercially available 6-hydroxy-4,5
diaminopyrimidine hemisulfate or 4,5-diaminopyrimidine. All title compounds were
investigated for their UV filtering, antioxidant, antifungal, and
antiproliferative activities. For the photoprotection assays we used a diffuse
transmittance technique to determine the sun protection factor (SPF) in vitro,
and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant
power (FRAP) tests for evaluating the antioxidant activity of the more potent
compounds. Among them, 8-(2,5-dihydroxyphenyl)-7H-purin-6-ol (compound 26) proved
to be a good radical scavenger and is also endowed with broad-spectrum UVA
filtering capabilities, suitable for further development as a protective
molecule.
PMID- 28417559
TI - Asenapine modulates mood-related behaviors and 5-HT1A/7 receptors-mediated
neurotransmission.
AB - AIM: Asenapine is a new atypical antipsychotic prescribed for the treatment of
psychosis/bipolar disorders that presents higher affinity for serotonergic than
dopaminergic receptors. The objective of this study was to investigate its
antidepressant-like and antimanic-like properties on relevant animal models of
depression and mania and to assess the acute and chronic effect of Asenapine on
dorsal raphe nucleus (DRN) 5-HT cell firing activity. METHODS: We assessed the
effects of Asenapine using in vivo electrophysiological and behavioral assays in
rats. RESULTS: Behavioral experiments showed that Asenapine had no significant
effect on immobility time in the forced swim test (FST) in control rats. In the
ACTH-treated rats, a model of antidepressant-resistance, Asenapine failed to
alter immobility time in the FST. In contrast in the sleep deprivation (SD) model
of mania, acute administration of Asenapine significantly decreased the
hyperlocomotion of SD rats. In the DRN, acute administration of Asenapine reduced
the suppressant effect of the selective 5-HT7 receptor agonist LP-44 and of the
prototypical 5-HT1A receptor agonist 8-OH-DPAT on 5-HT neuronal firing activity.
In addition, chronic treatment with Asenapine enhanced DRN 5-HT neuronal firing
and this effect was associated with an alteration of the 5-HT7 receptor
responsiveness. CONCLUSION: These results confirm that Asenapine displays robust
antimanic property and effective in vivo antagonistic activity at 5-HT1A/7
receptors.
PMID- 28417560
TI - Treatment of tumor in lymph nodes using near-infrared laser light-activated
thermosensitive liposome-encapsulated doxorubicin and gold nanorods.
AB - Tumor metastasis to lymph nodes is an important contributory factor for cancer
related deaths despite recent developments in cancer therapy. In this study, we
demonstrate that tumor in the proper axillary lymph node (PALN) of the mouse can
be treated by the application of external laser light to trigger the unloading of
doxorubicin (DOX) encapsulated in thermosensitive liposomes (TSLs) administered
together with gold nanorods (GNRs). GNRs + DOX-TSLs were injected into a mouse
lymph node containing cancer cells (malignant fibrous histiocytoma-like cells)
and intranodal DOX release was activated using near-infrared (NIR) laser
irradiation. The temperature changes arising from the laser-irradiated GNRs
triggered the release of DOX from the TSLs. A greater degree of inhibition of
tumor growth was found in the co-therapy group compared to the other groups. The
treatment effect was achieved by a combination of chemotherapy and NIR-activated
hyperthermia. In vivo bioluminescence imaging and histological analysis confirmed
tumor necrosis in response to combined treatment. This work presents a
theranostic approach with excellent treatment results that has the potential to
be developed into an alternative to surgery for the treatment of breast cancer
metastasis.
PMID- 28417561
TI - Population Pharmacokinetics of Morphine in Patients With Nonalcoholic
Steatohepatitis (NASH) and Healthy Adults.
AB - Altered expression and function of transporters in nonalcoholic steatohepatitis
(NASH) patients may affect the pharmacokinetics (PK), efficacy, and safety of
substrate drugs. A population pharmacokinetic (PopPK) analysis was performed to
assess differences in morphine and morphine-3-glucuronide (M3G) disposition in
NASH and healthy subjects. A total of 315 serum and 42 urine samples from 21
subjects (14 healthy; 7 NASH) were analyzed using NONMEM. Morphine and M3G PK
were described by three- and one-compartment models, respectively. After
accounting for the effect of total body weight on all clearance and volume of
distribution parameters using an allometric scaling approach, NASH severity score
(NASF; combination of fibrosis and nonalcoholic fatty liver disease activity
scores) was the most significant predictor of differences in M3G exposure. The
model predicted a linear decrease in the clearance of M3G with increasing NASF
scores on a natural logarithmic scale. These results may provide some insight
into the potential effect of NASH on the disposition of hepatic transporter
substrates.
PMID- 28417563
TI - Nutritional parameters as mortality predictors in haemodialysis: Differences
between genders.
AB - BACKGROUND: Malnutrition is common in patients undergoing haemodialysis (HD).
Several studies have described different nutritional parameters as mortality
predictors but few have studied whether there are differences between genders.
This study aimed to evaluate which nutrition parameters may be associated with
mortality in patients undergoing long-term HD depending on their gender. METHODS:
Longitudinal prospective multicentre study with 12 months of follow-up.
Anthropometric and laboratory measures were obtained from 697 patients. RESULTS:
Men who died were older, had lower dry weight, body mass index, potassium,
phosphorus and albumin, compared with male patients who survived. Female patients
who died had lower albumin and nPCR compared with survivors. Kaplan-Meier
analysis displayed a significantly worse survival in patients with albumin <3.5
g/dl in both genders and with body mass index <23 kg/m2 in men. In the Cox
regression analysis patients overall mortality was related to body mass index <23
kg/m2 , potassium <=5.5 mEq/l and phosphorus <3.0 mg/dl for male patients and
albumin <3.5 g/dl and normalised protein catabolic rate (nPCR) <0.8 g/kg/day for
both genders. Associations between albumin, body mass index and mortality risk
continued to be significant after adjustments for age, length of time on dialysis
and diabetes for males. However, in women, only albumin persisted as an
independent predictor of death. CONCLUSION: Depending on the gender, different
parameters such as protein intake, potassium, phosphorus, body mass index and
albumin are associated with mortality in patients undergoing HD. Albumin <3.5
g/dl is an independent mortality predictor in both genders, whereas a body mass
index <23 kg/m2 is an independent predictor of death, but only in men.
PMID- 28417562
TI - Climate variability drives recent tree mortality in Europe.
AB - Tree mortality is an important process in forest ecosystems, frequently
hypothesized to be highly climate sensitive. Yet, tree death remains one of the
least understood processes of forest dynamics. Recently, changes in tree
mortality have been observed in forests around the globe, which could profoundly
affect ecosystem functioning and services provisioning to society. We describe
continental-scale patterns of recent tree mortality from the only consistent pan
European forest monitoring network, identifying recent mortality hotspots in
southern and northern Europe. Analyzing 925,462 annual observations of 235,895
trees between 2000 and 2012, we determine the influence of climate variability
and tree age on interannual variation in tree mortality using Cox proportional
hazard models. Warm summers as well as high seasonal variability in precipitation
increased the likelihood of tree death. However, our data also suggest that
reduced cold-induced mortality could compensate increased mortality related to
peak temperatures in a warming climate. Besides climate variability, age was an
important driver of tree mortality, with individual mortality probability
decreasing with age over the first century of a trees life. A considerable
portion of the observed variation in tree mortality could be explained by
satellite-derived net primary productivity, suggesting that widely available
remote sensing products can be used as an early warning indicator of widespread
tree mortality. Our findings advance the understanding of patterns of large-scale
tree mortality by demonstrating the influence of seasonal and diurnal climate
variation, and highlight the potential of state-of-the-art remote sensing to
anticipate an increased likelihood of tree mortality in space and time.
PMID- 28417564
TI - 3D in vivo imaging with extended-focus optical coherence microscopy.
AB - Optical coherence microscopy (OCM) has unique advantages of non-invasive 3D
imaging without the need of exogenous labels for studying biological samples.
However, the imaging depth of this technique is limited by the tradeoff between
the depth of focus (DOF) and high lateral resolution in Gaussian optics. To
overcome this limitation, we have developed an extended-focus OCM (xf-OCM)
imaging system using quasi-Bessel beam illumination to extend the DOF to ~100
MUm, about 3-fold greater than standard OCM. High lateral resolution of 1.6 MUm
ensured detailed identification of structures within live animal samples. The
insensitivity to spherical aberrations strengthened the capability of our xf-OCM
system in 3D biological imaging.
PMID- 28417565
TI - Treatment of advanced melanoma with laser immunotherapy and ipilimumab.
AB - Immunotherapy has become a promising modality for melanoma, especially using
checkpoint inhibitors, which revive suppressed T cells against the cancer. Such
inhibitors should work better when combined with other treatments which could
increase the number and quality of anti-tumor T cells. We treated one patient
with advanced (stage IV) melanoma, using the combination of laser immunotherapy
(LIT), a novel immunological approach for metastatic cancers that has been shown
to stimulate adaptive immunity, and ipilimumab. The patient was treated with LIT,
followed with one course of ipilimumab 3 months after the beginning of LIT. After
LIT treatment, all treated cutaneous melanoma in head and neck cleared
completely. After the application of ipilimumab, all the tumor nodules in the
lungs decreased. The patient had remained tumor free for one year. While
anecdotal, the responses seen in this patient support the hypothesis that laser
immunotherapy increases the number and quality of anti-tumor T cells so that
ipilimumab and other checkpoint inhibitors are more effective in enhancing the
therapeutic effects. Picture: Schematic of treatment using laser immunotherapy
and ipilimumab on a stage IV melanoma patient.
PMID- 28417566
TI - Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for
Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.
AB - Cannabis sativa withdrawal syndrome is characterized mainly by psychological
symptoms. By using computational tools, the aim of this study was to propose drug
candidates for treating withdrawal syndrome based on the natural ligands of the
cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n
pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive
predictions as a human CB1 ligand and for facile synthetic accessibility.
Therefore, ZINC1730183 is a favorable candidate scaffold for further research
into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome.
PMID- 28417567
TI - A Versatile and Simple Approach to Generate Light Emission in Semiconductors
Mediated by Electric Double Layers.
AB - The light-emitting device is the primary device for current light sources. In
principle, conventional light-emitting devices need heterostructures and/or
intentional carrier doping to form a p-n junction. This junction formation is,
however, very difficult to achieve for most emerging semiconductors, and the
fabrication of light-emitting devices is invariably a significant challenge. This
study proposes a versatile and simple approach to realize light-emitting devices.
This proposed device requires only a semiconducting film with two electrodes that
are covered with an electrolyte. This unique structure achieves light emission at
a voltage slightly larger than the bandgap energy of materials. This study
applies this concept to emerging direct bandgap semiconductors, such as
transition metal dichalcogenide monolayers and zinc oxide single crystals. These
devices generate obvious light emission and provide sufficient evidence of the
formation of a dynamic p-i-n junction or tunneling junction, presenting a
versatile technique to develop optoelectronic devices.
PMID- 28417569
TI - Lessons from a violent death: The heart & soul of change.
PMID- 28417570
TI - Championing the National Strategic Framework for Rural and Remote Health.
PMID- 28417568
TI - Cisplatin-resistant cancer cells are sensitive to Aurora kinase A inhibition by
alisertib.
AB - De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a
clinical challenge in gastric cancer treatment. Aberrant expression and
activation of aurora kinase A (AURKA) and eukaryotic translation initiation
factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated
the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis
demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and
de novo CDDP-resistant gastric cancer models. Inhibition of AURKA with MLN8237
(alisertib) alone or in combination with CDDP significantly suppressed viability
of CDDP-resistant cancer cells (P < 0.01). Additionally, inhibition or knockdown
of AURKA decreased protein expression of p-eIF4E (S209), HDM2, and c-MYC in CDDP
resistant cell models. This was associated with a significant decrease in cap
dependent translation levels (P < 0.01). In vivo tumor xenografts data
corroborated these results and confirmed that inhibition of AURKA was sufficient
to overcome CDDP resistance in gastric cancer. Our data demonstrate that AURKA
promotes acquired and de novo resistance to CDDP through regulation of p-eIF4E
(S209), c-MYC, HDM2, and cap-dependent translation. Targeting AURKA could be an
effective therapeutic approach to overcome CDDP resistance in refractory gastric
cancer and possibly other cancer types.
PMID- 28417571
TI - A health commission for regional, rural and remote Australia.
PMID- 28417572
TI - John Humphreys.
PMID- 28417573
TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 18/2017.
PMID- 28417574
TI - Light-Emitting Diode treatment ameliorates allergic lung inflammation in
experimental model of asthma induced by ovalbumin.
AB - Since asthma is a multifactorial disease where treatment sometimes is not
effective, new therapies that improve the respiratory discomfort of patients are
of great importance. Phototherapy as Light-emitting diode (LED) has emerged as a
treatment that presents good results for diseases that are characterized by
inflammation. Thus, our objective was to investigate the effects of LED on lung
inflammation, by an evaluation of lung cell infiltration, mucus secretion,
oedema, and the production of cytokines. Male Balb/c mice were or not sensitized
and challenged with ovalbumin (OVA) and treated or not with LED therapy (1 h and
4 h after each OVA challenge). Twenty-four hours after the last OVA challenge,
analyzes were performed. Our results showed that LED treatment in asthmatic mice
reduced the lung cell infiltration, the mucus production, the oedema, and the
tracheal's contractile response. It also increased the IL-10 and the IFN-gamma
levels. The effects of LED treatment on lung inflammation may be modulated by IL
10, IFN-gamma, and by mast cells. This study may provide important information
about the effects of LED, and in addition, it may open the possibility of a new
approach for the treatment of asthma.
PMID- 28417575
TI - Effect of weight reduction on glycated haemoglobin in weight loss trials in
patients with type 2 diabetes.
AB - AIM: To quantify the effect of weight loss on glycated haemoglobin (HbA1c) at
group level, based on data from published weight loss trials in overweight and
obese patients with type 2 diabetes (T2D). METHODS: A systematic literature
search in MEDLINE, EMBASE and Cochrane CENTRAL (January 1990 through December
2012) was conducted to identify prospective trials of energy-reduced diets,
obesity drugs or bariatric surgery in adult, overweight and obese patients with
T2D. Based on clinical data with follow-up from 3 to 24 months, a linear model
was developed to describe the effect of weight reduction on HbA1c. RESULTS: The
literature search identified 58 eligible articles consisting of 124 treatment
groups and 17 204 subjects, yielding a total of 250 data points with concurrent
mean changes from baseline in weight and HbA1c. The model-based analyses
indicated a linear relationship between weight loss and HbA1c reduction, with an
estimated mean HbA1c reduction of 0.1 percentage points for each 1 kg of reduced
body weight for the overall population. Baseline HbA1c was a significant
covariate for the relationship between weight loss and HbA1c: high HbA1c at
baseline was associated with a greater reduction in HbA1c for the same degree of
weight loss. The collected trial data also indicated weight-loss-dependent
reductions in antidiabetic medication. CONCLUSIONS: At group level, weight loss
in obese and overweight patients with T2D was consistently accompanied by HbA1c
reduction in a dose-dependent manner. The model developed in the present study
estimates that for each kg of mean weight loss, there is a mean HbA1c reduction
of 0.1 percentage points. HbA1c-lowering is greater in populations with poor
glycaemic control than in well controlled populations with the same degree of
weight loss. This summary of data from previous trials regarding the effect of
weight reduction on HbA1c may be used to support the design and interpretation of
future studies that aim to demonstrate the efficacy of weight loss interventions
for T2D treatment.
PMID- 28417576
TI - The Relation between Chemical Bonding and Ultrafast Crystal Growth.
AB - Glasses are often described as supercooled liquids, whose structures are
topologically disordered like a liquid, but nevertheless retain short-range
structural order. Structural complexity is often associated with complicated
electron-charge distributions in glassy systems, making a detailed investigation
challenging even for short-range structural order, let alone their atomic
dynamics. This is particularly problematic for lone-pair-rich, semiconducting
materials, such as phase-change materials (PCMs). Here, this study shows that
analytical methods for studying bonding, based on the electron-charge density,
rather than a conventional atomic pair-correlation-function approach, allows an
in-depth investigation into the chemical-bonding network, as well as lone pairs,
of the prototypical PCM, Ge2 Sb2 Te5 (GST). It is demonstrated that the
structurally flexible building units of the amorphous GST network, intimately
linked to the presence of distinctly coexisting weak covalent and lone-pair
interactions, give rise to cooperative structural-ordering processes, by which
ultrafast crystal growth becomes possible. This finding may universally apply to
other PCMs.
PMID- 28417577
TI - Metal Hydride Nanoparticles with Ultrahigh Structural Stability and Hydrogen
Storage Activity Derived from Microencapsulated Nanoconfinement.
AB - Metal hydrides (MHs) have recently been designed for hydrogen sensors, switchable
mirrors, rechargeable batteries, and other energy-storage and conversion-related
applications. The demands of MHs, particular fast hydrogen absorption/desorption
kinetics, have brought their sizes to nanoscale. However, the nanostructured MHs
generally suffer from surface passivation and low aggregation-resisting
structural stability upon absorption/desorption. This study reports a novel
strategy named microencapsulated nanoconfinement to realize local synthesis of
nano-MHs, which possess ultrahigh structural stability and superior desorption
kinetics. Monodispersed Mg2 NiH4 single crystal nanoparticles (NPs) are in situ
encapsulated on the surface of graphene sheets (GS) through facile gas-solid
reactions. This well-defined MgO coating layer with a thickness of ~3 nm
efficiently separates the NPs from each other to prevent aggregation during
hydrogen absorption/desorption cycles, leading to excellent thermal and
mechanical stability. More interestingly, the MgO layer shows superior gas
selective permeability to prevent further oxidation of Mg2 NiH4 meanwhile
accessible for hydrogen absorption/desorption. As a result, an extremely low
activation energy (31.2 kJ mol-1 ) for the dehydrogenation reaction is achieved.
This study provides alternative insights into designing nanosized MHs with both
excellent hydrogen storage activity and thermal/mechanical stability exempting
surface modification by agents.
PMID- 28417579
TI - Sleep disorders require a comprehensive evaluation and confirmation with
polysomnography in patients with multiple sclerosis.
PMID- 28417580
TI - Response to Xia et al.
PMID- 28417581
TI - Radiopacity of Resin Cements Using Digital Radiography.
AB - STATEMENT OF PROBLEM: Monitoring performance of glass-ceramic based indirect
restorations using radiographic imaging might be difficult due to their low
radiopacity. Therefore, materials used for their cementation must possess
adequate radiopacity. PURPOSE: This study determined radiopacity of a group of
resin-cements used for adhesive-cementation of glass-ceramic-based restorations
using digital radiography. METHODS: Two specimens were prepared from a group of
resin cements (VariolinkII-opaque, VariolinkII-opaque (base), VariolinkII
Transparent, VariolinkII-Transparent (base), Nexus, RelyX Unicem, RelyX ultimate,
Duolink, Monocem and Resinomer) and longitudinal sections of same thickness were
obtained from molar and premolar. Specimens were assigned to two groups one had
molar section with 10 specimens whereas other had premolar with remaining 10
specimens. Each group was placed on digital radiograph sensor (Schick CDR, size
2) together with aluminum step-wedge. Sensor was exposed to X-ray using standard
technique. Two images were obtained for each group. Pixel measurements were made
using NIH Image-J software. Mean pixel measurements were converted into aluminum
thickness equivalents. Data were statistically-analyzed using one-way ANOVA and
Tukey's tests. RESULTS: ANOVA revealed significant difference in mean pixel
values among cements (p < 0.001). VariolinkII-opaque showed highest mean aluminum
equivalent (4.6 mm Al/1 mm) followed by VariolinkII-opaque-Base (4.5 mm Al/1 mm),
VariolinkII-transparent (4.45 mm Al/1 mm), VariolinkII-transparent-Base (4.45 mm
Al/1 mm), Nexus (2.95 mm Al/1 mm), Duolink (2.7 mm Al/1 mm), RelyX Unicem (2.2 mm
Al/1 mm) and finally RelyX ultimate (2 mm Al/1 mm). All cements had mean
radiopacity values higher than that of enamel whereas Monocem (1.25 mm Al/1 mm)
and Resinomer (1.2 mm Al/1 mm) had means between those of enamel and dentin.
CONCLUSIONS: All tested resin-cements showed radiopacity values higher than that
of dentin which is adequate for diagnostic purposes according to ISO
recommendation. CLINICAL SIGNIFICANCE: The use of resin cement with adequate
radiopacity for adhesive cementation of glass-ceramic based restorations enables
their radiographic monitoring. (J Esthet Restor Dent 29:215-221, 2017).
PMID- 28417582
TI - Hierarchical TiO2 /SnO2 Hollow Spheres Coated with Graphitized Carbon for High
Performance Electrochemical Li-Ion Storage.
AB - A self-templated strategy is developed to fabricate hierarchical TiO2 /SnO2
hollow spheres coated with graphitized carbon (HTSO/GC-HSs) by combined sol-gel
processes with hydrothermal treatment and calcination. The as-prepared mesoporous
HTSO/GC-HSs present an approximate yolk-double-shell structure, with high
specific area and small nanocrystals of TiO2 and SnO2 , and thus exhibit superior
electrochemical reactivity and stability when used as anode materials for Li-ion
batteries. A high reversible specific capacity of about 310 mAh g-1 at a high
current density of 5 A g-1 can be achieved over 500 cycles indicating very good
cycle stability and rate performance.
PMID- 28417583
TI - Ethnic differences in the pathogenesis of obstructive sleep apnoea: Exploring non
anatomical factors.
PMID- 28417584
TI - IR-spectroscopy of skin in vivo: Optimal skin sites and properties for non
invasive glucose measurement by photoacoustic and photothermal spectroscopy.
AB - We have reported two methods to analyze glucose in the interstitial fluid of skin
based on mid-infrared excitation with a tunable quantum cascade laser and
photoacoustic or photothermal detection. These methods were evaluated for optimum
skin locations to obtain reproducible glucose information. The lower part of the
arm, the hypothenar, the tips of the index finger and the thumb were tested. The
thumb appears to be the optimal skin location, followed by the index finger.
Basic requirements for an optimum site are good capillary blood perfusion, low
Stratum corneum thickness and the absence of fat layers. To obtain a correlation
on such a site, spectra were recorded on volunteers continuously after blood
glucose manipulation. However, continuous measurements on an in vivo sample such
as the skin have to cope with physiological alterations such as the formation of
sweat. We have used both detection schemes to investigate the acid mantle
reformation after washing during time scales similar to continuous measurements
for calibration spectra. We found that reconstitution of the acid mantle of skin
may be seen in less than one hour. Precleaning of the measurement site may thus
be useful for intermittent, but not for long term continuous measurements.
PMID- 28417585
TI - Speckle variance optical coherence tomography of blood flow in the beating mouse
embryonic heart.
AB - Efficient separation of blood and cardiac wall in the beating embryonic heart is
essential and critical for experiment-based computational modelling and analysis
of early-stage cardiac biomechanics. Although speckle variance optical coherence
tomography (SV-OCT) relying on calculation of intensity variance over
consecutively acquired frames is a powerful approach for segmentation of fluid
flow from static tissue, application of this method in the beating embryonic
heart remains challenging because moving structures generate SV signal
indistinguishable from the blood. Here, we demonstrate a modified four
dimensional SV-OCT approach that effectively separates the blood flow from the
dynamic heart wall in the beating mouse embryonic heart. The method takes
advantage of the periodic motion of the cardiac wall and is based on calculation
of the SV signal over the frames corresponding to the same phase of the heartbeat
cycle. Through comparison with Doppler OCT imaging, we validate this speckle
based approach and show advantages in its insensitiveness to the flow direction
and velocity as well as reduced influence from the heart wall movement. This
approach has a potential in variety of applications relying on visualization and
segmentation of blood flow in periodically moving structures, such as mechanical
simulation studies and finite element modelling. Picture: Four-dimensional
speckle variance OCT imaging shows the blood flow inside the beating heart of an
E8.5 mouse embryo.
PMID- 28417586
TI - ICU mortality is increased with high admission serum osmolarity in all patients
other than those admitted with pulmonary diseases and hypoxia.
AB - BACKGROUND AND OBJECTIVE: High serum osmolarity has been shown to be lung
protective. There is lack of clinical studies evaluating the impact on outcomes
such as mortality. We aimed to examine the effect of serum osmolarity on
intensive care unit (ICU) mortality in critically ill patients METHODS: Data from
January 2000 to December 2012 was accessed using the Australian and New Zealand
Intensive Care Society (ANZICS) Clinical Outcomes and Resource Evaluation (CORE)
database. A total of 509 180 patients were included. Serum osmolarity was
calculated from data during the first 24 h of ICU admission. Predefined subgroups
(Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic codes),
including patients with acute pulmonary diagnoses, were examined. The effect of
serum osmolarity on ICU mortality was assessed with analysis adjusted for illness
severity (serum sodium, glucose and urea component removed) and year of
admission. Results are presented as OR (95% CI) referenced against a serum
osmolarity of 290-295 mmol/L. RESULTS: The ICU mortality was elevated at each
extremes of serum osmolarity (U-shaped relationship). A similar relationship was
found in various subgroups, with the exception of patients with pulmonary
diagnoses in whom ICU mortality was not influenced by high serum osmolarity and
was different from other non-pulmonary subgroups (P < 0.01). Any adverse
associations with high serum osmolarity in pulmonary patients were confined to
patients with a PaO2 /FiO2 ratio > 200. CONCLUSION: High admission serum
osmolarity was not associated with increased odds for ICU death in pulmonary
patients, unlike other subgroup of patients, and could be a potential area for
future interventional therapy.
PMID- 28417587
TI - Healthcare utilization and spending by children with cancer on Medicaid.
AB - BACKGROUND: Children with cancer are a unique patient population with high
resource, complex healthcare needs. Understanding their healthcare utilization
could highlight areas for care optimization. PROCEDURE: We performed a
retrospective, cross-sectional analysis of the 2014 Truven Marketscan Medicaid
Database to explore clinical attributes, utilization, and spending among children
with cancer who were Medicaid enrollees. Eligible patients included children
(ages 0-18 years) with cancer (Clinical Risk Group 8). Healthcare utilization and
spending (per member per month, PMPM) were assessed overall and across specific
healthcare services. RESULTS: Children with cancer (n = 5,405) represent less
than 1% of the 1,516,457 children with medical complexity in the dataset.
Children with cancer had high services use: laboratory/radiographic testing
(93.0%), outpatient specialty care (83.4%), outpatient therapy/treatment (53.4%),
emergency department (43.7%), hospitalization (31.5%), home healthcare (9.5%).
PMPM spending for children with cancer was $3,706 overall and $2,323 for hospital
care. CONCLUSION: Children with cancer have high healthcare resource use and
spending. Differences in geographic distribution of services for children with
cancer and the trajectory of spending over the course of therapy are areas for
future investigation aimed at lowering costs of care without compromising on
health outcomes.
PMID- 28417588
TI - A Scalable and Versatile Synthesis of Oxime-Based Hormone Dimers and Gels for
Sustained Release.
AB - Well-defined steroid hormone dimers and organogels were produced via a facile and
scalable synthesis using oxime click chemistry. The versatile synthetic procedure
extends to a wide range of hormones and linker groups exemplified here through
the synthesis of cortisol- and progesterone-dimers linked via hydrophobic,
hydrophilic or functional groups. This method was also extended to the synthesis
of cortisone-based organogels. Owing to the dynamic nature of the oxime bond, the
hormone-based materials are degradable via acidic hydrolysis and transoximination
representing new materials for the controlled release of steroid hormones.
PMID- 28417589
TI - Glutathione-stabilized Cu nanocluster-based fluorescent probe for sensitive and
selective detection of Hg2+ in water.
AB - In this paper, an innovative and facile one-pot method for synthesizing water
soluble and stable fluorescent Cu nanoclusters (CuNCs), in which glutathione
(GSH) served as protecting ligand and ascorbic acid (AA) as reducing agent was
reported. The resultant CuNCs emitted blue-green fluorescence at 440 nm, with a
quantum yield (QD) of about 3.08%. In addition, the prepared CuNCs exhibited
excellent properties such as good water solubility, photostability and high
stability toward high ionic strength. On the basis of the selective quenching of
Hg2+ on CuNCs fluorescence, which may be the result of Hg2+ ion-induced
aggregation of the CuNCs, the CuNCs was used for the selective and sensitive
determination of Hg2+ in aqueous solution. The proposed analytical strategy
permitted detection of Hg2+ in a linear range of 4 * 10-8 to 6 * 10-5 M, with a
detection limit of 2.2 * 10-8 M. Eventually, the practicability of this sensing
approach was confirmed by its successful application to assay Hg2+ in tap water,
Lotus lake water and river water samples with the quantitative spike recoveries
ranging from 96.9% to 105.4%.
PMID- 28417590
TI - Calcitonin gene-related peptide (CGRP): A novel target for Alzheimer's disease.
AB - Alzheimer's disease (AD) is leading cause of death among older characterized by
neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and
increased levels of amyloid-beta (Abeta) peptides. Cholinergic treatment could be
the best suitable physiological therapy for AD. Calcitonin gene-related peptide
(CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from
different merging of the CGRP gene, which also includes adrenomedullin, amylin,
calcitonin, intermedin, and calcitonin receptor-stimulating peptide. It is a
proof for a CGRP receptor within nucleus accumbens of brain that is different
from either the CGRP1 or CGRP2 receptor in which it demonstrates similar high
affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is
not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases
activated cAMP-dependent pkA and PI3 kinase, resulting in N-terminal fragments
that are shown to exert complex inhibitory as well facilitator actions on nAChRs.
Fragments such as CGRP1-4, CGRP1-5, and CGRP1-6 rapidly as well as reversibly
improve agonist sensitivity of nAChRs without straight stimulating those
receptors and produce the Ca2+ -induced intracellular Ca2+ mobilization. Renin
angiotensin-aldosterone system (RAAS)-activated angiotensin-type (AT4) receptor
is also beneficial in AD. It has been suggested that exogenous administration of
CGRP inhibits infiltration of macrophages and expression of various inflammatory
mediators such as NFkB, IL-1b, TNF-alpha, iNOS, matrix metalloproteinase (MMP)-9,
and cell adhesion molecules like intercellular adhesion molecule (ICAM)-1 which
attenuates consequence of inflammation in AD. Donepezil, a ChEI, inhibits
acetylcholinesterase and produces angiogenesis and neurogenesis, in the dentate
gyrus of the hippocampus of WT mice after donepezil administration. However, none
of the results discovered in CGRP-knockout mice and WT mice exposed to practical
denervation. Therefore, selective agonists of CGRP receptors may become the
potential candidates for treatment of AD.
PMID- 28417591
TI - Effective mosquito and arbovirus surveillance using metabarcoding.
AB - Effective vector and arbovirus surveillance requires timely and accurate
screening techniques that can be easily upscaled. Next-generation sequencing
(NGS) is a high-throughput technology that has the potential to modernize vector
surveillance. When combined with DNA barcoding, it is termed 'metabarcoding.' The
aim of our study was to establish a metabarcoding protocol to characterize pools
of mosquitoes and screen them for virus. Pools contained 100 morphologically
identified individuals, including one Ross River virus (RRV) infected mosquito,
with three species present at different proportions: 1, 5, 94%. Nucleic acid
extracted from both crude homogenate and supernatant was used to amplify a 269-bp
section of the mitochondrial cytochrome c oxidase subunit I (COI) locus.
Additionally, a 67-bp region of the RRV E2 gene was amplified from synthesized
cDNA to screen for RRV. Amplicon sequencing was performed using an Illumina
MiSeq, and bioinformatic analysis was performed using a DNA barcode database of
Victorian mosquitoes. Metabarcoding successfully detected all mosquito species
and RRV in every positive sample tested. The limits of species detection were
also examined by screening a pool of 1000 individuals, successfully identifying
the species and RRV from a single mosquito. The primers used for amplification,
number of PCR cycles and total number of individuals present all have effects on
the quantification of species in mixed bulk samples. Based on the results, a
number of recommendations for future metabarcoding studies are presented.
Overall, metabarcoding shows great promise for providing a new alternative
approach to screening large insect surveillance trap catches.
PMID- 28417593
TI - Anomalous Resistance Hysteresis in Oxide ReRAM: Oxygen Evolution and
Reincorporation Revealed by In Situ TEM.
AB - The control and rational design of redox-based memristive devices, which are
highly attractive candidates for next-generation nonvolatile memory and logic
applications, is complicated by competing and poorly understood switching
mechanisms, which can result in two coexisting resistance hystereses that have
opposite voltage polarity. These competing processes can be defined as regular
and anomalous resistive switching. Despite significant characterization efforts,
the complex nanoscale redox processes that drive anomalous resistive switching
and their implications for current transport remain poorly understood. Here,
lateral and vertical mapping of O vacancy concentrations is used during the
operation of such devices in situ in an aberration corrected transmission
electron microscope to explain the anomalous switching mechanism. It is found
that an increase (decrease) in the overall O vacancy concentration within the
device after positive (negative) biasing of the Schottky-type electrode is
associated with the electrocatalytic release and reincorporation of oxygen at the
electrode/oxide interface and is responsible for the resistance change. This
fundamental insight presents a novel perspective on resistive switching processes
and opens up new technological opportunities for the implementation of memristive
devices, as anomalous switching can now be suppressed selectively or used
deliberately to achieve the desirable so-called deep Reset.
PMID- 28417595
TI - Influence of demographic characteristics on attenuated positive psychotic
symptoms in a young, help-seeking, at-risk population.
AB - AIM: Presentation of attenuated positive psychotic symptoms (APS) was reported to
be modestly influenced by age, sex and education in a psychosis-risk sample. We
re-examined the influence of demographic variables on APS in an independent
psychosis-risk sample. METHOD: In a clinical high-risk-sample (N = 188; 13-35
years; 60.1% men), bivariate correlations were examined with Spearman
correlations. All other associations were computed with generalized linear
models. RESULTS: Inter-correlations between positive symptoms were statistically
significant for all but the smallest coefficient (range: r = 0.12-0.49). Age was
negatively related to APS (range: OR = 0.53-0.78, all P < .01). Male sex was
uniquely related to disorganized communication (OR = 1.46) and a high education
level related negatively to suspiciousness/persecutory ideas (OR = 0.64),
perceptual abnormalities/hallucinations (OR = 0.57) and disorganized
communication (OR = 0.54). The variance explained by age ranged from R 2 = 0.044
for unusual thought content to R 2 = 0.144 for perceptual abnormalities.
CONCLUSION: Our results highlighted the role of age and, thereby,
neurodevelopment in psychosis-risk assessment.
PMID- 28417594
TI - Real-world supported unprotected left main percutaneous coronary intervention
with impella device; data from the USpella registry.
AB - BACKGROUND: Patients with left main (LM) coronary artery disease are increasingly
being treated with percutaneous revascularization (PCI). The safety, feasibility,
and efficacy of unprotected LM intervention (ULMI) with hemodynamic support by
Impella device have not been evaluated previously. OBJECTIVE: Using a large
retrospective single center database from the USpella registry, we evaluated the
safety, feasibility, and potential benefits of periprocedural left ventricular
assist with axial flow Impella 2.5 and Impella CP (Abiomed Inc. Danvers, Mass)
during ULMI. METHODS: We analyzed a total of 127 consecutive patients who
received hemodynamic support with Impella (2.5 or CP) for ULMI from August 2008
to July 2015. Safety, feasibility and efficacy end points included procedural
success rates, in-hospital and 30-day major adverse cardiovascular event (MACE)
rates. RESULTS: Among 127 patients who received hemodynamic support for ULMI
(mean age 69.98 +/- 10.7 years, 71% men, and mean left ventricular ejection
fraction 28.74 +/- 15.55%, Society of Thoracic Surgeons' mortality/morbidity
4/23%) the in-hospital and 30 days mortality rates were 1.43% (2/140) and 2.1%
(3/141), respectively. The average baseline and post PCI (residual) syntax scores
were 31.4 and 7.86, respectively, (P < 0.001). Only one patient (0.8%) had
vascular complication that required surgery; 2.36% (3/127) had hematoma and 3.9%
(5/127) had bleeding that required transfusion. CONCLUSION: This large singe
center retrospective evaluation of USpella registry substantiates and strongly
supports the feasibility, safety, and hemodynamic usefulness of Impella device
for ULMI with acceptable in-hospital and 30-day MACE rates. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28417592
TI - Individualising the dose of allopurinol in patients with gout.
AB - AIMS: The aims of the study were to: 1) determine if a plasma oxypurinol
concentration-response relationship or an allopurinol dose-response relationship
best predicts the dose requirements of allopurinol in the treatment of gout; and
2) to construct a nomogram for calculating the optimum maintenance dose of
allopurinol to achieve target serum urate (SU) concentrations. METHODS: A
nonlinear regression analysis was used to examine the plasma oxypurinol
concentration- and allopurinol dose-response relationships with serum urate. In
81 patients (205 samples), creatinine clearance (CLCR ), concomitant diuretic use
and SU concentrations before (UP ) and during (UT ) treatment were monitored
across a range of allopurinol doses (D, 50-700 mg daily). Plasma concentrations
of oxypurinol (C) were measured in 47 patients (98 samples). Models (n = 47
patients) and predictions from each relationship were compared using F-tests, r2
values and paired t-tests. The best model was used to construct a nomogram.
RESULTS: The final plasma oxypurinol concentration-response relationship (UT =
UP - C*(UP - UR )/(ID50 + C), r2 = 0.64) and allopurinol dose-response
relationship (UT = UP - D* (UP - UR )/(ID50 + D), r2 = 0.60) did not include
CLCR or diuretic use as covariates. There was no difference (P = 0.87) between
the predicted SU concentrations derived from the oxypurinol concentration- and
allopurinol dose-response relationships. The nomogram constructed using the
allopurinol dose-response relationship for all recruited patients (n = 81
patients) required pretreatment SU as the predictor of allopurinol maintenance
dose. CONCLUSIONS: Plasma oxypurinol concentrations, CLCR and diuretic status are
not required to predict the maintenance dose of allopurinol. Using the nomogram,
the maintenance dose of allopurinol estimated to reach target concentrations can
be predicted from UP .
PMID- 28417596
TI - Compressing Carbon Nanocages by Capillarity for Optimizing Porous Structures
toward Ultrahigh-Volumetric-Performance Supercapacitors.
AB - High volumetric energy density combined with high power density is highly desired
for electrical double-layer capacitors. Usually the volumetric performance is
improved by compressing carbon material to increase density but at the much
expense of power density due to the deviation of the compressed porous structure
from the ideal one. Herein the authors report an efficient approach to increase
the density and optimize the porous structure by collapsing the carbon nanocages
via capillarity. Three samples with decreasing sizes of meso- and macropores
provide us an ideal model system to demonstrate the correlation of volumetric
performance with porous structure. The results indicate that reducing the surplus
macropores and, more importantly, the surplus mesopores is an efficient strategy
to enhance the volumetric energy density while keeping the high power density.
The optimized sample achieves a record-high stack volumetric energy density of 73
Wh L-1 in ionic liquid with superb power density and cycling stability.
PMID- 28417597
TI - Ultrahigh-Water-Content, Superelastic, and Shape-Memory Nanofiber-Assembled
Hydrogels Exhibiting Pressure-Responsive Conductivity.
AB - High-water-content hydrogels that are both mechanically robust and conductive
could have wide applications in fields ranging from bioengineering and electronic
devices to medicine; however, creating such materials has proven to be extremely
challenging. This study presents a scalable methodology to prepare superelastic,
cellular-structured nanofibrous hydrogels (NFHs) by combining alginate and
flexible SiO2 nanofibers. This approach causes naturally abundant and sustainable
alginate to assemble into 3D elastic bulk NFHs with tunable water content and
desirable shapes on a large scale. The resultant NFHs exhibit the integrated
properties of ultrahigh water content (99.8 wt%), complete recovery from 80%
strain, zero Poisson's ratio, shape-memory behavior, injectability, and elastic
responsive conductivity, which can detect dynamic pressure in a wide range (>50
Pa) with robust sensitivity (0.24 kPa-1 ) and durability (100 cycles). The
fabrication of such fascinating materials may provide new insights into the
design and development of multifunctional hydrogels for various applications.
PMID- 28417599
TI - High Dielectric Performances of Flexible and Transparent Cellulose Hybrid Films
Controlled by Multidimensional Metal Nanostructures.
AB - Various wearable electronic devices have been developed for extensive outdoor
activities. The key metrics for these wearable devices are high touch sensitivity
and good mechanical and thermal stability of the flexible touchscreen panels
(TSPs). Their dielectric constants (k) are important for high touch
sensitivities. Thus, studies on flexible and transparent cover layers that have
high k with outstanding mechanical and thermal reliabilities are essential.
Herein, an unconventional approach for forming flexible and transparent cellulose
nanofiber (CNF) films is reported. These films are used to embed ultralong metal
nanofibers that serve as nanofillers to increase k significantly (above 9.2 with
high transmittance of 90%). Also, by controlling the dimensions and aspect ratios
of these fillers, the effects of their nanostructures and contents on the optical
and dielectric properties of the films have been studied. The length of the
nanofibers can be controlled using a stretching method to break the highly
aligned, ultralong nanofibers. These nanofiber-embedded, high-k films are
mechanically and thermally stable, and they have better Young's modulus and
tensile strength with lower thermal expansion than commercial transparent
plastics. The demonstration of highly sensitive TSPs using high-k CNF film for
smartphones suggests that this film has significant potential for next
generation, portable electronic devices.
PMID- 28417598
TI - Genetic analysis of a morphologically heterogeneous ovarian endometrioid
carcinoma.
AB - AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade
components. Whether the latter are clonally related to and originate from the low
grade endometrioid carcinoma remains unclear. The aim of this study was to use
massively parallel sequencing to characterize the genomic landscape and clonal
relatedness of an ovarian endometrioid carcinoma containing low-grade and high
grade components. METHODS AND RESULTS: DNA samples extracted from each tumour
component (low-grade endometrioid, high-grade anaplastic and high-grade squamous)
and matched normal tissue were subjected to targeted massively parallel
sequencing with the 410-gene Memorial Sloan Kettering-Integrated Mutation
Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay. Somatic
single nucleotide variants, small insertions and deletions, and copy number
alterations were detected with state-of-the-art bioinformatics algorithms, and
validated with orthogonal methods. The endometrioid carcinoma and the associated
high-grade components shared copy number alterations and four clonal mutations,
including SMARCA4 mutations, which resulted in loss of BRG1 protein expression.
Subclonal mutations and mutations restricted to single components were also
identified, such as distinct TP53 mutations restricted to each histological
component. CONCLUSIONS: Histologically distinct components of ovarian
endometrioid carcinomas may show intratumour genetic heterogeneity but be
clonally related, harbouring a complex clonal composition. In the present case,
SMARCA4 mutations were probably early events, whereas TP53 somatic mutations were
acquired later in evolution.
PMID- 28417601
TI - Abstracts of the Seventh Annual Meeting of the Associazione Italiana Sistema
Nervoso Periferico (ASNP) April 20-22, 2017 Bergamo, Italy.
PMID- 28417600
TI - A Bioinspired Mineral Hydrogel as a Self-Healable, Mechanically Adaptable Ionic
Skin for Highly Sensitive Pressure Sensing.
AB - In the past two decades, artificial skin-like materials have received increasing
research interests for their broad applications in artificial intelligence,
wearable devices, and soft robotics. However, profound challenges remain in terms
of imitating human skin because of its unique combination of mechanical and
sensory properties. In this work, a bioinspired mineral hydrogel is developed to
fabricate a novel type of mechanically adaptable ionic skin sensor. Due to its
unique viscoelastic properties, the hydrogel-based capacitive sensor is
compliant, self-healable, and can sense subtle pressure changes, such as a gentle
finger touch, human motion, or even small water droplets. It might not only show
great potential in applications such as artificial intelligence, human/machine
interactions, personal healthcare, and wearable devices, but also promote the
development of next-generation mechanically adaptable intelligent skin-like
devices.
PMID- 28417602
TI - Novel use of perfusion balloon inflation to avoid outflow tract obstruction
during transcatheter mitral valve-in-valve replacement.
AB - Left ventricular outflow tract (LVOT) obstruction is a recognized complication of
transcatheter mitral valve-in-valve replacement in previous surgical prostheses.
We describe a patient who was high risk for repeat open surgery in whom the LVOT
was compromised by a surgical strut and the potential for LVOT obstruction. A
novel approach to avoiding this complication was utilized. A perfusion balloon
was inflated in the outflow tract to provide an opposing force during mitral
valve deployment resulting in less flaring of the strut into the outflow tract
thereby improving the neo-LVOT area. No outflow tract obstruction occurred. The
advantages of this approach as well as other alternative solutions to this
problem are discussed. (c) 2017 Wiley Periodicals, Inc.
PMID- 28417603
TI - Squamate Conserved Loci (SqCL): A unified set of conserved loci for phylogenomics
and population genetics of squamate reptiles.
AB - The identification of conserved loci across genomes, along with advances in
target capture methods and high-throughput sequencing, has helped spur a
phylogenomics revolution by enabling researchers to gather large numbers of
homologous loci across clades of interest with minimal upfront investment in
locus design. Target capture for vertebrate animals is currently dominated by two
approaches-anchored hybrid enrichment (AHE) and ultraconserved elements (UCE)-and
both approaches have proven useful for addressing questions in phylogenomics,
phylogeography and population genomics. However, these two sets of loci have
minimal overlap with each other; moreover, they do not include many traditional
loci that that have been used for phylogenetics. Here, we combine across UCE, AHE
and traditional phylogenetic gene locus sets to generate the Squamate Conserved
Loci set, a single integrated probe set that can generate high-quality and highly
complete data across all three loci types. We use these probes to generate data
for 44 phylogenetically disparate taxa that collectively span approximately 33%
of terrestrial vertebrate diversity. Our results generated an average of 4.29 Mb
across 4709 loci per individual, of which an average of 2.99 Mb was sequenced to
high enough coverage (>=10*) to use for population genetic analyses. We validate
the utility of these loci for both phylogenomic and population genomic questions,
provide a comparison among these locus sets of their relative usefulness and
suggest areas for future improvement.
PMID- 28417604
TI - Rotational atherectomy in the subadventitial space to allow safe and successful
chronic total occlusion recanalization: Pushing the limit further.
AB - Dissection and re-entry (DR) techniques have played a key role in the increase of
success rates of chronic total occlusion (CTO) recanalization. DR usually allows
wiring complex occlusions, even in case of important calcification. In extreme
cases, such as in balloon failure-to-cross, rotational atherectomy (RA) might be
decisive. However, according to experts' recommendations, RA should not be
performed in dissection planes because of the high risk of perforation and
further extending the dissection, so that its use after DR might be limited.
Here, we describe a case of successful right coronary artery CTO recanalization
in which, after failure of several antegrade and retrograde techniques, RA was
safely performed antegradely in the subadventitial space, thus eventually
enabling reverse controlled antegrade and retrograde subintimal tracking (CART).
Although the feasibility of RA in CTO percutaneous coronary intervention had
already been suggested, this case reports on the novel use of RA to allow further
manipulation of the subadventitial space (reverse CART) prior to successful
recanalization. (c) 2017 Wiley Periodicals, Inc.
PMID- 28417607
TI - Rebuttal: Adverse outcome of coarctation stenting in patients with Turner
syndrome.
PMID- 28417606
TI - Caboxamycin biosynthesis pathway and identification of novel benzoxazoles
produced by cross-talk in Streptomyces sp. NTK 937.
AB - Streptomyces sp. NTK937, producer of benzoxazole antibiotic caboxamycin, produces
in addition a methyl ester derivative, O-methylcaboxamycin. Caboxamycin cluster,
comprising one regulatory and nine structural genes, has been delimited, and each
gene has been individually inactivated to demonstrate its role in the
biosynthetic process. The O-methyltransferase potentially responsible for O
methylcaboxamycin synthesis would reside outside this cluster. Five of the genes,
cbxR, cbxA, cbxB, cbxD and cbxE, encoding a SARP transcriptional regulator,
salicylate synthase, 3-oxoacyl-ACP-synthase, ACP and amidohydrolase,
respectively, have been found to be essential for caboxamycin biosynthesis. The
remaining five structural genes were found to have paralogues distributed
throughout the genome, capable of partaking in the process when their cluster
homologue is inactivated. Two of such paralogues, cbxC' and cbxI', coding an AMP
dependent synthetase-ligase and an anthranilate synthase, respectively, have been
identified. However, the other three genes might simultaneously have more than
one paralogue, given that cbxF (DAHP synthase), cbxG (2,3-dihydro-2,3
dihydroxybenzoate dehydrogenase) and cbxH (isochorismatase) have three, three and
five putative paralogue genes, respectively, of similar function within the
genome. As a result of genetic manipulation, a novel benzoxazole (3'
hydroxycaboxamycin) has been identified in the salicylate synthase-deficient
mutant strain DeltacbxA. 3'-hydroxycaboxamycin derives from the cross-talk
between the caboxamycin and enterobactin pathways.
PMID- 28417608
TI - Comparison of antithrombotic agents during urgent percutaneous coronary
intervention following thrombolytic therapy: A retrospective cohort study.
AB - BACKGROUND: The optimal antithrombotic regimen for urgent percutaneous coronary
interventions (PCI) following thrombolytic therapy for ST segment myocardial
infarction (STEMI) is currently unknown. METHODS: We performed a retrospective
analysis of all patients referred to our institution from January 2005 to July
2014 who underwent urgent PCI within 24 hr after receiving thrombolytic therapy.
The patients were divided into three cohorts based on the anticoagulation
strategy during PCI-bivalirudin, heparin alone or heparin plus Glycoprotein
IIb/IIIa inhibitor (GPI). The primary end point of major adverse cardiovascular
events (MACE) was defined as a composite of inpatient death, myocardial
infarction (MI) and stroke. Net adverse clinical events (NACE) were defined as a
combination of MACE plus major bleeding complications. Univariable, multivariable
and propensity-weighted modeling were used to compare MACE and NACE between the
three treatment groups. RESULTS: A total of 695 patients met the inclusion
criteria during the study period. In the univariable analysis, there was no
significant difference treatment in MACE between the three groups (Bivalirudin:
1.2% vs. Heparin + GPI: 4.4%; Heparin alone: 2.7%, P = 0.11). In the reduced
logistic regression model, compared to bivalirudin, the odds of NACE was
significantly higher with heparin alone (OR: 3.58, 95% CI: 1.21, 10.54, P = 0.02)
or with heparin plus GPI (OR: 9.0, 95% CI: 2.83, 28.64, P <0.001). CONCLUSION: In
STEMI patients undergoing PCI within 24 hr after thrombolytic therapy,
bivalirudin was associated with a strong trend toward reduced bleeding
complications as compared to heparin alone or heparin plus GPI. The optimal
antithrombotic regiment for urgent PCI following thrombolytic therapy is
currently unknown. Our study demonstrated that use of bivalirudin during PCI
following thrombolytic therapy is associated with a trend toward reduced bleeding
complications compared to heparin alone or heparin plus GPI. Large randomized
trials of adjunctive anticoagulation during PCI in this complex post-thrombolytic
population are warranted. (c) 2017 Wiley Periodicals, Inc.
PMID- 28417609
TI - Action plans and coping strategies in elderly COPD patients influence the result
of pulmonary rehabilitation: an observational study.
AB - BACKGROUND: COPD management needs a comprehensive assessment of clinical features
(symptoms severity, co-morbidities) together with life-style, behavioural, socio
economic and multi-omics parameters. Among the other issues, psycho-cognitive
assessment plays a critical role. Coping strategies are used to manage
psychological stress. AIM: To evaluate the association between coping strategies
and outcome of Pulmonary Rehabilitation (PR). DESIGN: Observational study.
SETTING: Inpatients comprehensive 3 weeks PR programme. POPULATION: Seventy-six
patients, 70 years or older affected by COPD GOLD 3-4. METHODS: Disease-specific
status was examined using the Medical Research Council Dyspnea Scale, St.
George's Respiratory Questionnaire, Maugeri Respiratory Failure, Borg And Barthel
Scales. Cognitive And Psychological Clinical Alterations/Disorders Using: Mini
Mental State Examination; Montreal Cognitive Assessment; Center for Epidemiologic
Studies Depression Scale; Zung Self-Rating Anxiety Scale. Quality of Life Using
Activities of Daily Living; Instrumental Activities of Daily Living; 36-Item
Short Form Health Survey General and Mental Health. Functional exercise capacity
was measured at baseline and after PR using the Six-Minute Walking Test (6MWT).
Coping strategies were measured with the Brief COPE. Internal consistency was
determined examining Cronbach's alpha values. Concurrent validity was determined
by examining Spearman r correlations between the single-item and multi-items.
Brief-COPE scores after PR between patients who had a different response to
respiratory outcomes was evaluated using Student's t and Mann-Whitney U tests.
RESULTS: The change in distance (Delta6MWD) between final and baseline value in
meters was positively associated with Self-distraction, Active Coping, and
Planning strategies. Respiratory disease-specific health status outcomes, as well
as the presence of use of long-term oxygen therapy, were not associated with
coping strategies. CONCLUSIONS: Self-distraction and Planning strategies are
associated to the success of rehabilitation. CLINICAL REHABILITATION IMPACT: Self
distraction and Planning strategies may predict response to pulmonary
rehabilitation in elderly patients affected by severe COPD.
PMID- 28417610
TI - Functional outcome of critical illness polyneuropathy in patients affected by
severe brain injury.
AB - BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) frequently occur
in intensive care unit (ICU) critically ill subjects; about 55-70% of subjects
achieve full recovery. CIPNM can occur in ICU subjects with severe acquired brain
injury (sABI), but no data have been reported regarding their outcome. AIM: The
aim of the present study was to investigate the functional recovery in subjects
suffering from both CIPNM and sABI and whether they had poorer outcome than those
with sABI only. DESIGN: Prospective cohort study. SETTING: Dedicated
rehabilitation setting. POPULATION: Adult ICU subjects with sABI causing a
disorder of consciousness graded 3-8 on the Glasgow Coma Scale admitted to a
dedicated rehabilitative setting were enrolled from January 2015 to June 2016.
METHODS: The enrolled sample was divided in two groups: patients with CIPNM and
coexistent sABI (CIPNM+sABI) and patients with sABI. Electromyography was
performed in all subjects to ascertain CIPNM occurrence, at admission. Functional
outcome was investigated using the Rancho Los Amigos Levels of Cognitive
Functioning (LCF), Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS) and
modified Rankin Scale (mRS), at admission and discharge. Mortality and length of
stay (LOS) were recorded. RESULTS: One-hundred and thirty-one patients (59 F, 72
M; mean age 54.7+/-15.8) were admitted to the rehabilitation setting, and 111 (47
F, 64 M; mean age: 53.6+/-18.4 years) were enrolled. Thirty-six (31.8%) had
CIPNM+sABI, and 75 patients had isolated sABI. Significant functional outcomes in
all assessment measures were observed after rehabilitation in all samples. The
estimated mean scores (95% confidence interval) of LCF, DRS, GOS and mRS from a
multivariate model adjusted for age, sex and time of ICU stay were: 2.85 (2.53
3.21) and 5.24 (4.81-5.71), 23.94 (22.37-25.62) and 16.04 (14.77-17.41), 2.86
(2.70-3.04) and 3.46 (3.28-3.65), and 4.91 (4.67-5.17) and 3.79 (3.58-4.02), at
admission and at discharge, respectively. Despite functional improvement,
CIPNM+sABI patients showed lesser improvement than those with sABI only.
Furthermore, patients with both disorders had significantly higher median LOS
than sABI subjects: 107 (q1-q3: 65-146), and 65 (q1-q3: 38-105) days (P=5.5x10
83), respectively. No statistically significant difference in mortality rates was
found between groups. CONCLUSIONS: Subjects with CIPNM and coexistent sABI
improved after rehabilitation, but had poorer recovery than those with solely
sABI requiring a longer LOS. CLINICAL REHABILITATION IMPACT: The rehabilitation
process in subjects suffering from CINPM is challenging and no evidence support
the use of specific rehabilitative approaches to improve function and activities
of daily living.
PMID- 28417611
TI - Factors enhancing activities of daily living after stroke in specialized
rehabilitation: an observational multicenter study within the Sunnaas
International Network.
AB - BACKGROUND: Stroke may lead to serious, long-term disability. Consequently, many
individuals with stroke will be in need of rehabilitation, and some of
specialized rehabilitation. The content and organization of rehabilitation vary
within and between countries, reflecting the preferences, customs, traditions,
and values of a society or community, that may have an impact on outcomes. The
main aim of the present study was to evaluate the influence of team models in
specialized rehabilitation on outcomes as measured by stroke patients'
performance in activities of daily living (ADL), at a standardized time and at
discharge in the various specialized rehabilitation clinics. Secondary aims were
to identify explanatory factors for possible differences in ADL changes at
standardized time points. DESIGN: A prospective descriptive cross-sectional
explorative, multicenter study. SETTING: Specialized rehabilitation clinics in
Norway, China, the USA, Russia, Israel, Palestine, and Sweden, for a total of
nine clinics. POPULATION: Persons with stroke. METHODS: Outcomes measures were
the modified Rankin Scale (mRS) and the National Institute of Health Stroke Scale
(NIHSS), both on admission and at discharge from the inpatient rehabilitation
unit, and Barthel Index (BI) or alternatively Functional Independence Measure
(FIM), on admittance, 18-22 days into rehabilitation, at discharge, and at 6 and
12 months after discharge. RESULTS: In total 230 stroke patients from nine
clinics were recruited. There were significant differences in change scores of
ADL from admittance to standardized time point 18-22 days into rehabilitation,
(P<0.001, R2=0.19) and when controlled for baseline NIHSS and mRS (P<0.001,
R2=0.18; P=0.01, R2=0.9 respectively). Analysis divided into intra-, multi- and
interdisciplinary models showed significant differences at 18-22 days (P=0.02)
and at discharge (P<0.001), indicating a more favorable outcome in ADL with the
multi-disciplinary model. The linear regression analysis explained 55% of the
changes in ADL (R2=0.55) at the standardized time point and 48% (R2=0.48) at
discharge. Main explanatory factors were disability (mRS) and severity (NIHSS),
team models, hours in therapy, and location at discharge. ADL was maintained for
the majority of participants at 6 and 12 months post discharge. The correlations
mRS/ADL (r=-0.68, P<0.0001), NIHSS/ADL (r=-0.55, P<0.0001) and NIHSS/mRS (r=0.46,
P<0.0001) disclosed medium to large associations at 18-22 days into
rehabilitation. CONCLUSIONS: The study indicates that the organization of
services in specialized rehabilitation after stroke has a major impact on
improvement of ADL outcomes. Main positive predictive factors were models of
teamwork, with the multidisciplinary model as most beneficial, and concentrated
hours of therapy. Negative predictors were the level of baseline severity and
disability post stroke. CLINICAL REHABILITATION IMPACT: The results indicate that
organization of services should be at target to optimize patients' outcomes in
rehabilitation. Furthermore, that concentrated hour's related to specific goals
in therapy are preferable to optimize functional recovery.
PMID- 28417612
TI - Fatigue and its relationship with physical activity in adolescents and young
adults with traumatic brain injury: a cross-sectional study.
AB - BACKGROUND: Physical activity (PA) in patients with traumatic brain injury (TBI)
may be impaired leading to secondary health issues and limitations in
participation. AIM: This study aims to determine the level of PA and its
determinants in adolescents and young adults with TBI. DESIGN: Cross-sectional
survey study. SETTING: Outpatient clinic of a rehabilitation center. POPULATION:
Discharged patients aged 12-39 years with a diagnosis of TBI >6 months treated in
the rehabilitation center between 2009-2012. METHODS: The Activity Questionnaire
for Adults and Adolescents (AQuAA) measuring PA, with results dichotomized for
meeting or not meeting Dutch recommendations for health-enhancing physical
activity (D-HEPA) and the Checklist Individual Strength questionnaire (CIS; range
20-140, higher scores represent higher levels of fatigue), measuring fatigue,
were administered. RESULTS: Fifty (47%) of the 107 invited patients completed the
questionnaire. Mean age was 25.0+/-7.2 years and 22 (44%) were male. Eighteen
(36%) had a mild injury, 13 (26%) a moderate injury and 19 (38%) a severe injury.
Median time spent on moderate-vigorous physical activity was 518 minutes/week
(IQR 236-1725) (males performing significantly more minutes on moderate-vigorous
activity than women) and on sedentary activity 2728 minutes/week (IQR 1637-3994).
Thirty-two (64%) participants met the D-HEPA. According to the CIS, 19
participants (38%) were severely fatigued. Both the CIS total score and the
subscales motivation and physical activity were associated with meeting the D
HEPA. CONCLUSIONS: The proportion of individuals with TBI meeting D-HEPA was
similar to the general population, with the PA level being associated with self
reported fatigue. CLINICAL REHABILITATION IMPACT: Physical activity programs are
continuously being developed to increase the percentage of individuals meeting
public health recommendations for PA; when developing programs for individuals
with TBI extra consideration should be taken for the presence of fatigue. As in
the general population, females with TBI are less active, PA programs should
probably consider gender differences in their development.
PMID- 28417613
TI - Combination therapy for complex peripheral artery disease: the evidence for
combining mechanical revascularization with anti-restenotic drug delivery
systems.
AB - The management of complex, lower-extremity peripheral artery disease remains a
difficult challenge, with ample room for improvement in the results seen with
current generation devices. Therapies which use a combination of multiple devices
for their mechanical and anti-restenotic properties may be advantageous, and
offer an opportunity to improve the durability of revascularization through
optimizing and individualizing care. Combination therapy typically utilizes drug
delivery devices in addition to stents and atherectomy to achieve improved
results. However, there is a paucity of high-level evidence with which to direct
treatment, with many different forms of combination therapy under investigation
and little clinical research coordination. Herein we seek to describe and
evaluate the growing number of options for combination treatment in this
challenging disease.
PMID- 28417614
TI - Spinal epidural abscess caused by Brucella species: a review of 17 cases.
AB - BACKGROUND: Spinal epidural abscess (SEA) is a rarely encountered clinical entity
during the course of Brucella infection. METHODS: We reported 17 patients
diagnosed with Brucellar SEA for a mean follow-up of 15 months. Spinal epidural
abscess was detected by magnetic resonance imaging in all cases. Brucella
diagnosis was established by serological tests. Patients were administered
antibiotics for duration of 6 to 16 weeks. RESULTS: SEA was localized in lumbar
region in 9 patients, thoracic in 4 patients, cervical in 3 patients, both
thoracic and lumbar in 1 patient. Neurologic examination was normal in 4
patients, we detected motor and/or sensory deficit in 13 patients. Symptoms
regressed in all patients after the institution of antibiotic regimens, and all
recovered fully. Surgical drainage of abscess was performed in 2 patients and 3
patients were performed limited laminectomies. CONCLUSIONS: Antibiotic therapy
could be primary treatment and is effective in required doses and duration for
many patients. If neurologic deterioration be observed despite proper antibiotic
regimens in required doses and duration, surgical intervention is to be
performed.
PMID- 28417615
TI - Granular cell tumor of the orbit: pathological features and treatment.
PMID- 28417616
TI - Cervical radiculopathy caused by vertebral artery loop.
PMID- 28417617
TI - Indocyanine green videoangiography: the thin border between a useful tool and an
illusion of safety.
PMID- 28417618
TI - Indocyanine green videoangiography application in distal (M4) middle cerebral
artery aneurysm surgery.
PMID- 28417619
TI - Human Leukocyte Antigen (HLA) Class I and II Polymorphism in Iranian Healthy
Population from Yazd Province.
AB - The major histocompatibility complex (MHC) genes are the most polymorphic loci in
the human genome and have been widely studied in various populations and ethnic
groups. Investigations into the HLA genes and proteins have been useful tool for
anthropological, transplantation and disease association studies. The
polymorphism of the HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1) genes
were investigated in 90 unrelated Iranian individuals from Yazd province located
in the center of Iran using sequence-specific primers (PCR-SSP). Allele and
haplotype frequencies, expected/observed heterozygosity, unbiased expected
heterozygosity, number of effective alleles, deviations from Hardy-Weinberg (HW)
equilibrium and genetic diversity were computed. A total of 23, 48, 23, 24, 13
and 16 alleles for HLA-A, -B,-C, -DRB1, -DQA and -DQB loci were determined,
respectively in the population study. The most frequent allele identified in this
study were A*02:01 (18.889%), HLA-B* 51:01 (12.778%), HLA-C* 12:03 (17.033%), HLA
DRB* 11 (24.4%), HLA-DQA* 05:05 (20.55%) and HLA-DQB*03:01 (22.8%).Furthermore,
the most frequent 3-locus haplotypes were DRB*11-DQA*05:01-DQB*03:01 (21.1%), HLA
A*02:01- B *50:01- DRB*07:01 (4.9%) and A*26:01 -B* 38:01 -C*12:03(5%). The most
4-locus haplotype were A*11:01 -B* 52:01 -C*12:03 -DRB!*15(2.5%) and A*02:01 -B*
50:01 -DRB1*07:01 -DQB1*02:01(4.5%). The heterozygosity of the study population
was confirmed the expected value and not deviated from Hardy-Weinberg equilibrium
for all loci (p>0.05). Our study shows a close relatedness between Yazd
population and other ethnic group of Iran despite some differences, which may be
due to admixture of each one of these groups with each other or foreigner
subpopulations during centuries. Moreover, the results of this study suggest that
the Iranian population from Yazd province is in close vicinity with the
Caucasians populations and far from the Korean and Japanese populations.
PMID- 28417620
TI - Effects of Submaximal Aerobic Exercise on Regulatory T Cell Markers of Male
Patients Suffering from Ischemic Heart Disease.
AB - There are confirmed beneficiary effects of exercise on atherosclerotic
inflammation of ischemia-associated heart diseases. The purpose of this study was
to evaluate the effect of aerobic exercise on T-regulatory cell markers of IL-35
as well as FoxP3 and T-helper2 marker of IL-33 in patients with ischemic heart
disease (IHD). This research was performed on 44 asymptomatic male patients with
ischemic heart disease. The participants were randomly assigned into two groups
of submaximal aerobic exercise and control group. Blood samples were collected
before and after the termination of the exercise protocol. Serum levels of IL-35
and IL-33 as well as the amount of FoxP3 gene expression in peripheral blood
mononuclear cells were measured by Elisa and Real time PCR, respectively. Serum
levels of IL-35 (p=0.001) as well as the amount of FoxP3 gene expression
increased significantly (p=0.012) in exercise group even after controlling the
likely confounding effects of age, length of ischemia, duration of the disease,
and the amount of such factors before exercise (p<=0.042). It seems that exercise
may yield a better control of atherosclerotic inflammation in patients with
ischemic heart disease through the induction of regulatory T cells.
PMID- 28417621
TI - Inverse Relation between MxA Gene Expression and Age in Multiple Sclerosis
Patients Reveals a Gender Difference in Response to Interferon Therapy.
AB - Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease
of the central nervous system that women are at a higher risk to acquire than
men. Myxovirus resistance protein A (MxA) is used as a predictive marker of
bioactivity of interferon-beta (IFN-beta) therapy in MS patients. This study was
undertaken in west of Iran to investigate gender differences in the expression
level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-beta
therapy, compared with untreated normal individuals. The expression level of the
MxA gene in RRMS samples were compared to untreated normal individuals using the
extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and
50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15
negative and responded to IFN-beta with a normal vitamin D level. The level of
MxA gene expression was measured by quantitative RT-PCR. The levels of gene
expression were decreased in RRMS patients compared with normal counterparts
(p=0.025). This decrease was significant in females (p=0.009) compared to males
(p>0.05). The level of expression varied across different female age-groups with
no significant difference in women younger than 30 years, but a significant
decrease in expression in women between 30 to 40 years or above 40 years of age
was seen. There was neither linear correlation between the MxA expression level
and risk of expanded disability status scale of Kurtzke (EDSS); nor were there
any significant correlation between expression status of MxA and duration of the
disease. In conclusion, the decrease in the level of MxA expression in MS
patients treated with IFN-beta when compared to normal individuals was
significantly lower in females than males. This demonstrated a gender bias in
the response to IFN-beta therapy that will need to be confirmed and further
investigated in more detail.
PMID- 28417622
TI - Anti-inflammatory Effects of Novel Thiazolidinone Derivatives as Bioactive
Heterocycles on RAW264.7 Cells.
AB - The inhibition of the inducible nitric oxide synthase (iNOS), cyclooxygenase 2
(COX-2) and nuclear factor-kappaB (NF-kappaB) production are research targets of
attract in the field of anti-inflammatory drug development. Therefore, this study
was designed to investigate the anti-inflammatory effects of novel thiazolidinone
derivatives using a cellular model of lipopolysaccharide (LPS)-stimulated murine
macrophage RAW 264.7. In the present study, five new derivatives (A to E) of
thiazolidinone were synthesized and screened for anti-inflammatory activities.
Cell viability of LPS-stimulated RAW 264.7 macrophages clearly decreased in >55
MUg/mL of synthesized A-E compounds especially in the presence of C; therefore,
up to 50 MUg/mL of compounds were selected for the subsequent analysis. A
majority of these compounds showed significant inhibition on the production of NO
in LPS-stimulated macrophages in a dose-dependent manner. Compounds B and D (10
50 MUg/mL) significantly inhibited LPS-induced NF-kappaB (p65) production in a
dose-dependent manner. The effects of B and D on iNOS and COX-2 mRNA and protein
expression in LPS-stimulated RAW 264.7 cells were detected by real time-PCR and
western blot. B derivative significantly suppressed the iNOS and COX-2 mRNA level
and as well as protein expression. Taken together, these results reveal that
compound B as new thiazolidinone derivative decreased expression of the
inflammatory-related signals (NO, iNOS and COX-2) through regulation of NF
kappaB; hence, this compound could be suggested as a novel therapeutic strategy
for inflammation-associated disorders.
PMID- 28417623
TI - A Real Life Comparison between Allergenic Extracts and Allergenic Molecules.
AB - Serum IgE assay is a mainstay step in the allergy work up. Allergenic extracts
and molecular components are available at present. This real life study compared
the serum specific IgE levels against allergenic extracts with allergenic
molecules in patients allergic to Parietaria, Betulaceae, and mites. This
retrospective real life study included 489 subjects with respiratory allergy.
Inclusion criteria were 1) documented diagnosis of allergic rhinitis (AR) and/or
allergic asthma, and 2) documented allergy to Parietaria judaica (Par j) 2 (216
patients: 112 females, mean age 42 years), or to Betula verrucosa (Bet v) 1 (62
patients: 35 females, mean age 3 years), or Dermatophagoides pteronyssinus (Der
p) 1 (211 patients: 107 females, mean age 34 years); and mono-allergy. Serum IgE,
specific both for total/crude allergen extracts and individual
purified/recombinant allergens, were assessed by ImmunoCap system. The serum IgE
levels to birch extract were very strongly (R2=0.96) related to IgE to Bet v 1.
There was a strong (R2=0.71) correlation between Dermatophagoides pteronyssinus
IgE and Der p 1. A very strong (R2=0.87) correlation also existed between
Parietaria extract IgE and Par j 2 IgE levels. However, there was discrepancy
between percentages of positivity between allergenic extracts and molecules.
Therefore, allergen molecular diagnostics may represent a useful way in allergy
work up, but deserves caution in particular circumstances.
PMID- 28417624
TI - Cow's Milk Desensitization in Anaphylactic Patients: A New Personalized-dose
Method.
AB - Cow's milk allergy (CMA) is the most frequent food allergy in children and oral
immunotherapy (OIT) is a promising approach for treatment of patients. The most
challenging cases are anaphylactic with coexisting asthma and proposing safe
protocols is crucial especially in high risk groups. Considering that CMA varies
among patients, an individualized OIT protocol would be beneficial to achieve a
safer and more efficient method of desensitization. 18 children more than 3 years
of age with IgE-mediated CMA were enrolled. CMA was confirmed by positive skin
prick test (SPT) and positive oral food challenge (OFC) and 60% of individuals
had a convincing history of persistent asthma. SPT with milk extracts, whole
fresh milk and serially diluted milk concentrations were performed. The dilution
of milk that induced 3-5 mm of wheal in each individual was selected as the
starting dilution for OIT. Desensitization began by 1 drop of the defined
dilution and continued increasingly. Overall, 16 out of 18 children (88.8%)
achieved the daily intake of 120 mL of milk. Four out of these 16 children
accomplished the protocol without any adverse allergic reactions. 12 patients
experienced mild to severe reactions. Wheal and erythema in SPT (p<=0.001), and
sIgE (p<=0.003) to most milk allergens were significantly decreased following
desensitization. We successfully desensitized 16 of 18 children with IgE-mediated
CMA by individualized desensitization protocol. Individualizing the OIT protocol
would be helpful to save time and perhaps to relieve the allergic symptoms after
ingesting cow's milk intake.
PMID- 28417625
TI - Influence of Sensitization Patterns on Fractional Exhaled Nitric Oxide in
Asthmatic Children.
AB - Fractional exhaled nitric oxide (FeNO) has been suggested as a non-invasive
biomarker of airway inflammation, which is increased in atopic subjects. Whether
sensitization to particular allergens is a predictive factor for increased FeNO
levels is not yet fully understood. We conducted a retrospective cross-sectional
study. From October to December in 2015, the medical documents of 127 mild,
steroid-naive asthmatic children and 34 healthy age-matched children were
enrolled in this study. The results of the FeNO measurements, skin prick test,
and the spirometry were collected for analysis. Sensitization patterns to the 18
aeroallergens (5 categories: mites, molds, animal dander, pollen, and other) were
determined in study population. A significant increase in FeNO level was observed
in poly-sensitized asthmatic children (34.7 part per billion, (ppb) [28.3-41.1
p.p.b]), compared with mono-sensitized asthmatics (30.7 p.p.b [18.3-43.2 p.p.b])
and with non-sensitized asthmatics (17.3 p.p.b [10.8-24.5 p.p.b]). With
sensitization to perennial allergens (mites, mold, and animal dander), blood
eosinophil counts were significantly associated with increased FeNO (p<0.05 for
all). The highest FeNO level was identified in children sensitized to a
combination of the perennial, seasonal, and other allergens, when compared with
those sensitized to one category of allergen alone (p=0.004). Our study showed
that variations in FeNO level were associated with individuals' sensitization
patterns. Being sensitized to some particular allergens might contribute to
prompt the airway inflammation.
PMID- 28417626
TI - Production and Characterization of Monoclonal Antibody against Recombinant Virus
Coat Protein CP42.
AB - There are many studies related to the production of a ELISA kit for diagnosing
virus infections. However, production of most kits depends on purification of
whole virus particles, which involves the use of costly equipment and reagents.
The purpose of this study was to check out if the anti-CP42 antibodies could be
used as a diagnostic assay for detection of Grapevine fanleaf Virus (GFLV). In
this study, recombinant GFLV coat protein gene related to selected antigenic
determinants was inserted into pET-28a bacterial expression vector and the
construct (pET-28a CP42) was cloned into E. coli strain (DE3). Expressed protein
was verified with western blotting assay by the use of commercially available
anti-GFLV antibody. The recombinant protein was purified using nickel
nitrilotriacetic acid (Ni-NTA) resin. Balb/c mice were immunized with purified
protein and splenocytes of hyperimmunized mice were fused with murine myeloma
Sp2/0 cells. Positive hybridomas were selected by ELISA using CP42 as coating
antigen. The results showed that monoclonal antibody (MAb) specific to CP42 has
been successfully generated. Efficiency of produced antibody was analyzed by
ELISA and western blotting assay using some confirmed grapevine samples. The
infection was confirmed previously based on morphological features and ELISA
assay, performed using commercial anti-GFLV antibody. The monoclonal antibody
reacted with antigen in ELISA and immunoblot method. Our results demonstrated
that anti recombinant CP42 monoclonal antibodies are able to diagnose whole virus
in infected grapevine sample using ELISA test.
PMID- 28417627
TI - A Retrospective Study on the Association between Thyroid Autoantibodies with
beta2-glycoprotein and Cardiolipin Antibodies in Recurrent Miscarriage.
AB - Etiologic factors for recurrent miscarriage (RM) include autoimmune diseases, the
most frequently antiphospholipid syndrome and thyroiditis. Some women who suffer
from RM might also have an altered immune system. We aimed to evaluate possible
associations between anti-thyroid and anti-phospholipid antibodies in women with
RM. In a retrospective case series 1 on 156 women with RM, major outcome
parameters were antibodies against cardiolipin, beta2-glycoprotein I,
thyreoperoxidase (TPO-Ab), and thyroglobulin (TG-Ab). Significant (p<0.05)
positive correlations were found between TPO-Ab and TG-Ab (r=0.577), TPO-Ab and
IgG anti-cardiolipin antibodies (r=0.284), TPO-Ab and IgG anti- beta2
glycoprotein I antibodies (r=0.196), and TG-Ab and IgG anti-cardiolipin
antibodies (r=0.193), as well as between all types of anti-phospholipid
antibodies. Women with both increased TPO-Ab and TG-Ab levels revealed higher
(p<0.001) IgG anti-cardiolipin and IgG anti-beta2-glycoprotein I antibodies. Anti
thyroid antibodies were linked to anti-phospholipid antibodies and should be in
the focus of future research on RM.
PMID- 28417629
TI - Symptom Severity and Allergen-specific IgE in Allergic Rhinitis.
AB - No Abstract##.
PMID- 28417628
TI - Role of Gut Microbiota and Infectious Burden in the Development of Autoimmune and
Allergic Diseases.
AB - No Abstract#.
PMID- 28417630
TI - Self-Healable and Reprocessable Polysulfide Sealants Prepared from Liquid
Polysulfide Oligomer and Epoxy Resin.
AB - Polysulfide sealants have been commercially applied in many industrial fields. In
this article, we study the self-healing property of the epoxy resin-cured
polysulfide sealants for the first time. The obtained sealants showed a flexible
range of ultimate elongation of 157-478% and a tensile strength of 1.02-0.75 MPa
corresponding to different polysulfide oligomers. By taking advantage of the
dynamic reversible exchange of disulfide bonds, polysulfide sealants exhibited
good self-healing ability under a moderate thermal stimulus. A higher molecular
weight and a lower degree of cross-linking of polysulfide oligomer were helpful
in improving the ultimate elongation and healing efficiency of the polysulfide
sealants. After subjecting to a temperature of 75 degrees C for 60 min, both the
tensile strength and ultimate elongation of a fully cut sample, LP55-F, were
restored to 91% of the original values, without affecting the sealing property.
Furthermore, the sample exhibited excellent reshaping and reprocessing abilities.
These outcomes offer a paradigm toward sustainable industrial applications of the
polysulfide-based sealants.
PMID- 28417631
TI - Inkjet-Printed Quantum Dot Light-Emitting Diodes with an Air-Stable Hole
Transport Material.
AB - High-efficiency quantum dot light-emitting diodes (QLEDs) were fabricated using
inkjet printing with a novel cross-linkable hole transport material N,N'-(9,9'
spirobi[fluorene]-2,7-diylbis[4,1-phenylene])bis(N-phenyl-4'-vinyl-[1,1'
biphenyl]-4-amine) (SDTF). The cross-linked SDTF film has excellent solvent
resistance, high thermal stability, and the highest occupied molecular orbital
(HOMO) level of -5.54 eV. The inkjet-printed SDTF film is very smooth and
uniform, with roughness as low as 0.37 nm, which is comparable with that of the
spin-coated film (0.28 nm). The SDTF films stayed stable without any pinhole or
grain even after 2 months in air. All-solution-processed QLEDs were fabricated;
the maximum external quantum efficiency of 5.54% was achieved with the inkjet
printed SDTF in air, which is comparable to that of the spin-coated SDTF in a
glove box (5.33%). Electrical stabilities of both spin-coated and inkjet-printed
SDTF at the device level were also investigated and both showed a similar
lifetime. The study demonstrated that SDTF is very promising as a printable hole
transport material for making QLEDs using inkjet printing.
PMID- 28417632
TI - Evidence of Multiple Sorption Modes in Layered Double Hydroxides Using Mo As
Structural Probe.
AB - Layered double hydroxides (LDHs) have been considered as effective phases for the
remediation of aquatic environments, to remove anionic contaminants mainly
through anion exchange mechanisms. Here, a combination of batch isotherm
experiments and X-ray techniques was used to examine molybdate (MoO42-) sorption
mechanisms on CaAl LDHs with increasing loadings of molybdate. Advanced modeling
of aqueous data shows that the sorption isotherm can be interpreted by three
retention mechanisms, including two types of edge sites complexes, interlayer
anion exchange, and CaMoO4 precipitation. Meanwhile, Mo geometry evolves from
tetrahedral to octahedral on the edge, and back to tetrahedral coordination at
higher Mo loadings, indicated by Mo K-edge X-ray absorption spectra. Moreover, an
anion exchange process on both CaAl LDHs was followed by in situ time-resolved
synchrotron-based X-ray diffraction, remarkably agreeing with the sorption
isotherm. This detailed molecular view shows that different uptake mechanisms
edge sorption, interfacial dissolution-reprecipitation-are at play and control
anion uptake under environmentally relevant conditions, which is contrast to the
classical view of anion exchange as the primary retention mechanism. This work
puts all these mechanisms in perspective, offering a new insight into the complex
interplay of anion uptake mechanisms by LDH phases, by using changes in Mo
geometry as powerful molecular-scale probe.
PMID- 28417633
TI - pH-Responsive Graphene Oxide-DNA Nanosystem for Live Cell Imaging and Detection.
AB - The interaction between graphene oxide (GO) and DNA is very sensitive to the
environment. For example, under acidic conditions, the affinity of GO for DNA is
enhanced, weakening the capability of GO to distinguish DNAs with different
conformations. This effect has impeded the development of sensitive pH biosensors
based on GO-DNA nanosystems. In this work, we systematically studied the affinity
between GO and i-motif forming oligonucleotides (IFOs) at different pH values and
developed a herring sperm DNA (HSD) treatment method. Using this method, HSD
occupies the surface of GO, compromising the attractive force of GO that is
significantly enhanced under acidic conditions. As a result, the ability of GO to
distinguish between "open" and "closed" IFOs is successfully generalized to a
wider pH range. Finally, a pH-sensitive GO-IFO nanosystem was fabricated that
showed excellent sensing ability both in vitro and for intracellular pH
detection. Because the interaction between GO and DNA is the basis for
constructing GO-DNA biosensors, the strategy developed in this work shows great
potential to be applied in a variety of other GO-DNA sensing systems.
PMID- 28417634
TI - Anti-influenza A Virus Activity of Dendrobine and Its Mechanism of Action.
AB - Dendrobine, a major component of Dendrobium nobile, increasingly draws attention
for its wide applications in health care. Here we explore potential effects of
dendrobine against influenza A virus and elucidate the underlying mechanism. Our
results indicated that dendrobine possessed antiviral activity against influenza
A viruses, including A/FM-1/1/47 (H1N1), A/Puerto Rico/8/34 H274Y (H1N1), and
A/Aichi/2/68 (H3N2) with IC50 values of 3.39 +/- 0.32, 2.16 +/- 0.91, 5.32 +/-
1.68 MUg/mL, respectively. Mechanism studies revealed that dendrobine inhibited
early steps in the viral replication cycle. Notably, dendrobine could bind to the
highly conserved region of viral nucleoprotein (NP), subsequently restraining
nuclear export of viral NP and its oligomerization. In conclusion, dendrobine
shows potential to be developed as a promising agent to treat influenza virus
infection. More importantly, the results provide invaluable information for the
full application of the Traditional Chinese Medicine named "Shi Hu".
PMID- 28417635
TI - Crystallization of Amphiphilic DNA C-Stars.
AB - Many emerging technologies require materials with well-defined three-dimensional
nanoscale architectures. Production of these structures is currently underpinned
by self-assembling amphiphilic macromolecules or engineered all-DNA building
blocks. Both of these approaches produce restricted ranges of crystal geometries
due to synthetic amphiphiles' simple shape and limited specificity, or the
technical difficulties in designing space-filling DNA motifs with targeted
shapes. We have overcome these limitations with amphiphilic DNA nanostructures,
or "C-Stars", that combine the design freedom and facile functionalization of DNA
based materials with robust hydrophobic interactions. C-Stars self-assemble into
single crystals exceeding 40 MUm in size with lattice parameters exceeding 20 nm.
PMID- 28417636
TI - Semifluorinated Synergistic Nonfouling/Fouling-Release Surface.
AB - The preparation of a fluorine-containing synergistic nonfouling/fouling-release
surface, using a b-PFMA-PEO asymmetric molecular brush possessing both
poly(ethylene glycol) (PEO) and poly(2,2,2-trifluoroethyl methacrylate) (PFMA)
side chains densely distributed on the same repeat unit along the polymeric
backbone, is reported. On the basis of the poly(Br-acrylate-alkyne) macroagent
comprising two functionalities (alkynyl and 2-bromopropionate), which is prepared
by reversible addition-fragmentation chain transfer homopolymerization of a new
trifunctional acrylate monomer of Br-acrylate-alkyne, b-PFMA-PEO asymmetric
molecular brushes are obtained by concurrent atom transfer radical polymerization
and Cu-catalyzed azide/alkyne cycloaddition "click" reaction in a one-shot
system. A spin-cast thin film of the b-PFMA-PEO asymmetric molecular brush
exhibits a synergistic antifouling property, in which PEO side chains endow the
surface with a nonfouling characteristic, whereas PFMA side chains display the
fouling-release functionality because of their low surface energy. Both protein
adsorption and cell adhesion tests provided estimates of the antifouling activity
of the asymmetric molecular brush surfaces, which was demonstrated to be
influenced by the degree of polymerization of the backbone and the length of the
PEO and PFMA side chains. With compositional heterogeneities, all asymmetric
molecular brush surfaces show considerable antifouling performance with much less
protein adsorption (at least 45% off, up to 75% off) and cell adhesion (at least
70% off, up to 90% off) in comparison with a bare surface.
PMID- 28417637
TI - Synergistic Enhancement of Microwave Absorption Using Hybridized
Polyaniline@helical CNTs with Dual Chirality.
AB - In this study, we designed a dual-chirality hierarchical structure to achieve a
synergistically enhanced effect in microwave absorption via the hybridization of
nanomaterials. Herein, polyaniline (PANi) nanorods with tunable chirality are
grown on helical carbon nanotubes (HCNTs), a typical nanoscale chiral structure,
through in situ polymerization. The experimental results show that the
hierarchical hybrids (PANi@HCNTs) exhibit distinctly dual chirality and a
significant enhancement in electromagnetic (EM) losses compared to those of
either pure PANi or HCNTs. The maximum reflection loss of the as-prepared hybrids
can reach -32.5 dB at 8.9 GHz. Further analysis demonstrates that combinations of
chiral acid-doped PANi and coiled HCNTs with molecular and nanoscale chirality
lead to synergistic effects resulting from the dual chirality. The so-called
cross-polarization may result in additional interactions with induced EM waves in
addition to multiscaled relaxations from functional groups and interfacial
polarizations, which can benefit EM absorption.
PMID- 28417638
TI - Mimicking Complex Biological Membranes and Their Programmable Glycan Ligands with
Dendrimersomes and Glycodendrimersomes.
AB - Synthetic vesicles have been assembled and coassembled from phospholipids, their
modified versions, and other single amphiphiles into liposomes, and from block
copolymers into polymersomes. Their time-consuming synthesis and preparation as
stable, monodisperse, and biocompatible liposomes and polymersomes called for the
elaboration of new synthetic methodologies. Amphiphilic Janus dendrimers (JDs)
and glycodendrimers (JGDs) represent the most recent self-assembling amphiphiles
capable of forming monodisperse, stable, and multifunctional unilamellar and
multilamellar onion-like vesicles denoted dendrimersomes (DSs) and
glycodendrimersomes (GDSs), dendrimercubosomes (DCs), glycodendrimercubosomes
(GDCs), and other complex architectures. Amphiphilic JDs consist of hydrophobic
dendrons connected to hydrophilic dendrons and can be thought of as monodisperse
oligomers of a single amphiphile. They can be functionalized with a variety of
molecules such as dyes, and, in the case of JGDs, with carbohydrates. Their
iterative modular synthesis provides efficient access to sequence control at the
molecular level, resulting in topologies with specific epitope sequence and
density. DSs, GDSs, and other architectures from JDs and JGDs serve as powerful
tools for mimicking biological membranes and for biomedical applications such as
targeted drug and gene delivery and theranostics. This Review covers all aspects
of the synthesis of JDs and JGDs and their biological activity and applications
after assembly in aqueous media.
PMID- 28417639
TI - A Simple Descriptor to Rapidly Screen CO Oxidation Activity on Rare-Earth Metal
Doped CeO2: From Experiment to First-Principles.
AB - Ceria (CeO2) is an attractive catalyst because of its unique properties, such as
facile redoxability and high stability. Thus, many researchers have examined a
wide range of catalytic reactions on ceria nanoparticles (NPs). Among those
contributions are the reports of the dopant-dependent catalytic activity of
ceria. On the other hand, there have been few mechanistic studies of the effects
of a range of dopants on the chemical reactivity of ceria NPs. In this study, we
examined the catalytic activities of pure and Pr, Nd, and Sm-doped CeO2 (PDC,
NDC, and SDC, respectively) NPs on carbon monoxide (CO) oxidation. Density
functional theory (DFT) calculations were also performed to elucidate the
reaction mechanism on rare-earth (RE)-doped CeO2(111). The experimental results
showed that the catalytic activities of CO oxidation were in the order of CeO2 >
PDC > NDC > SDC. This is consistent with the DFT results, where the reaction is
explained by the Mars-van Krevelen mechanism. On the basis of the theoretical
interpretation of the experimental results, the ionic radius of the RE dopant can
be used as a simple descriptor to predict the energy barrier at the rate
determining step, thereby predicting the entire reaction activity. Using the
descriptor, a wide range of RE dopants on CeO2(111) were screened for CO
oxidation. These results provide useful insights to unravel the CO oxidation
activity on various oxide catalysts.
PMID- 28417641
TI - Editorial for AVCC relaunch issue.
PMID- 28417640
TI - Combinations of L-NG-monomethyl-arginine and oseltamivir against pandemic
influenza A virus infections in mice.
AB - L-NG-monomethyl-arginine (L-NMMA) is an experimental compound that suppresses
nitric oxide production in animals. The compound was combined with oseltamivir to
treat lethal influenza A/California/04/2009 (H1N1) pandemic virus infections in
mice. Treatments were given twice a day for five days starting 4 h (oseltamivir,
by oral gavage) or three days (L-NMMA, by intraperitoneal route; corresponding to
the time previously reported for nitric oxide induction in the animals) after
infection. Low doses of oseltamivir were used in order to demonstrate synergy or
antagonism. Oseltamivir monotherapy protected 70% of mice from death at 1
mg/kg/day. L-NMMA (40 and 80 mg/kg/day) was ineffective alone in preventing
mortality. Compared to oseltamivir treatment alone, L-NMMA combined with
oseltamivir was synergistically effective (as evaluated by three-dimensional
MacSynergy analysis), resulting in survival increases from 20 to 70% when 40 or
80 mg/kg/day of L-NMMA was combined with 0.3 mg/kg/day of oseltamivir, and from
70 to 100% survival increases when these doses were combined with 1 mg/kg/day of
oseltamivir. These data demonstrate that a nitric oxide inhibitor such as L-NMMA
has the potential to be beneficial when combined with oseltamivir in treating
influenza virus infections.
PMID- 28417642
TI - Equilibrative nucleoside transporter 1 expression in primary human hepatocytes is
highly variable and determines uptake of ribavirin.
AB - Aims Ribavirin is a nucleoside analogue and remains a necessary component of both
interferon-based and directly acting anti-viral regimens for the treatment of
hepatitis C virus infection. The achievable concentration of ribavirin within
hepatocytes is likely to be an important determinant of therapeutic outcome. In
vitro expression levels of equilibrative nucleoside transporter 1 (ENT1) has been
shown to be a predictor of treatment response in patients receiving nucleoside
based chemotherapeutic agents. We therefore investigated whether a similar
relationship existed between ENT1 expression and ribavirin uptake in freshly
isolated primary hepatocytes. Methods Primary hepatocytes were cultured on
collagen-coated plates and exposed to ribavirin. Parallel samples were taken for
high-performance liquid chromatography to assess ribavirin uptake and for
quantitative polymerase chain reaction to evaluate ENT1 expression. Similar
assays were performed on the human hepatoma cell line (Huh7). ENT1 gene sequence
was analysed by cloning of polymerase chain reaction amplified complementary DNA
followed by direct sequencing. Results There was a strong direct correlation
between expression of ENT1 in primary hepatocytes and ribavirin uptake at 24 hr.
Huh7 cells expressed ENT1 at similar levels to the majority of primary
hepatocytes, but did not take up ribavirin. Sequencing revealed that ENT1 in Huh7
cells is wild type. Conclusions In this study, we clearly demonstrate that
ribavirin uptake in primary human hepatocytes is variable and correlates with
ENT1 expression. This variation in ENT1 expression may account for differences in
response rate in patients receiving ribavirin-based anti-hepatitis C virus
therapy.
PMID- 28417643
TI - Feeling bad about progress does not lead people want to change their health
behaviour.
AB - OBJECTIVE: When do people decide to do something about problematic health
behaviours? Theoretical models and pragmatic considerations suggest that people
should take action when they feel bad about their progress - in other words, when
they experience negative progress-related affect. However, the impact of progress
related affect on goal striving has rarely been investigated. DESIGN AND METHODS:
Study 1 (N = 744) adopted a cross-sectional design and examined the extent to
which measures of progress-related affect were correlated with intentions to take
action. Study 2 (N = 409) investigated the impact of manipulating progress
related affect on intentions and behaviour in an experimental design. RESULTS:
Study 1 found that, while engaging in health behaviours had the expected
affective consequences (e.g. people felt bad when they were not eating healthily,
exercising regularly or limiting their alcohol consumption), it was feeling good
rather than bad about progress that was associated with stronger intentions.
Study 2 replicated these findings. Participants induced to feel good about their
eating behaviour had marginally stronger intentions to eat healthily than
participants led to feel bad about their eating behaviour. CONCLUSION: The
findings have implications for interventions designed to promote changes in
health behaviour, as well as theoretical frameworks for understanding self
regulation.
PMID- 28417644
TI - Does Social Interaction Matter Psychological Well-Being in Persons With Dementia?
AB - BACKGROUND: Social interaction between residents and staff is an important factor
influencing sense of well-being. This study examined the relationship between
staff-resident interactions and psychological well-being of persons with
dementia. METHODS: A total of 831 observations of 110 persons with dementia in 17
nursing homes and 6 assisted living facilities were included. Psychological well
being was measured by observed displays of positive and negative emotional
expressions. Social interaction was determined by the type of social interaction
(ie, verbal interaction, nonverbal interaction, and both verbal and nonverbal
interactions) and the quality of interaction (ie, positive, negative, and
neutral). RESULTS: Verbal or both verbal and nonverbal interactions showed
significant relationship with positive and negative emotional expressions.
Positive interaction was significantly associated with more positive emotional
expression, whereas negative interaction was not. CONCLUSION: Staff-resident
interactions are important to promote the psychological well-being of persons
with dementia in residential care.
PMID- 28417645
TI - The early chain of care and risk of death in acute stroke in relation to the
priority given at the dispatch centre: A multicentre observational study.
AB - BACKGROUND: The early chain of care is critical for stroke patients. The most
important part is the so-called 'system delay' i.e. the delay time from call to
the emergency medical services until a diagnosis is established (computer
tomography). AIM: The purpose of this study was to relate the initial priority
level given by the dispatch centre to the early chain of care in acute stroke and
to short-term and long-term mortality. METHODS: All patients hospitalised with
the first and the final diagnosis of acute stroke, 15 December 2010-15 April
2011, were recruited across nine hospitals, each hospital with a stroke care
unit. RESULTS: In all, 897 stroke patients were included. Priority at the
dispatch centre: 54% received highest priority 1, 41% priority 2 and 5% priority
3. Median system delay from call to emergency medical services until diagnosis by
computer tomography was 2 h and 52 min, 4 h and 49 min and 6 h and 33 min
respectively in the three priority groups ( p<0.0001). There was a similarly
strong association between priority level at the dispatch centre and system delay
to arrival in a hospital ward, suspicion of stroke by the emergency medical
services nurse as well as the physician on hospital admission and the proportion
of patients given thrombolysis. Mortality during the subsequent 30 days was 22%
among patients with priority 1 and 14% among patients with priority 2.
CONCLUSION: Patients given a lower priority level at the dispatch centre had the
longest system delay. Although many of these patients died, the risk of death was
highest among those given the highest priority.
PMID- 28417646
TI - Cerebral hemodynamic assessment and neuroimaging across the lifespan in sickle
cell disease.
AB - Children and adults with sickle cell anemia (SCA) have a higher risk of strokes
compared to age- and race-matched peers. Velocity in the middle cerebral or
distal internal carotid artery as measured by transcranial Doppler ultrasound is
a recognized method to identify children but not adults with SCA at high-risk for
first stroke. For both children and adults with SCA that have had a stroke, no
methods clearly identify individuals at highest risk of recurrent strokes or an
initial silent stroke, the most common neurological injury. Methods to assess
cerebral hemodynamics in SCA have been utilized for decades but often required
radiotracers making them not feasible for screening and longitudinal follow-up.
MRI approaches that do not require exogenous contrast have been introduced and
are appealing in both clinical and research scenarios. Improved neuroimaging
strategies hold promise for identifying individuals with SCA at increased risk of
initial and recurrent infarcts, justifying more aggressive risk-based therapy. We
review the epidemiology of stroke in SCA, the impact of strokes, stroke
mechanisms, and potential imaging strategies including regional and global oxygen
extraction fraction, cerebral blood flow, and vessel wall imaging to identify
individuals at high-risk of stroke.
PMID- 28417647
TI - Mixed states in bipolar disorder - changes in DSM-5 and current treatment
recommendations.
AB - OBJECTIVE: Mixed states in affective disorders represent a particular challenge
in clinical routine, characterized by a complicated course of treatment and a
worse treatment response. METHODS: Clinical features of mixed states and the
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria are
presented and critical discussed. We then performed a systematic review using the
terms 'bipolar', 'mixed' and 'randomized' to evaluate current treatment options.
RESULTS: For pharmacological treatment of mixed states in total, there is still
insufficient data from RCTs. However, there is some evidence for efficacy in
mixed states from RCTs for atypical antipsychotics, especially olanzapine,
aripiprazole and asenapine as well as mood stabilizers as valproate and
carbamazepine. CONCLUSIONS: Mixed states are of a high clinical relevance and the
DSM-5 criteria substantially reduced the diagnostic threshold. Besides advantages
of a better characterization of patients with former DSM-IV-defined mixed
episodes, disadvantages arise for example differential diagnoses with a
substantial overlap in symptoms such as borderline personality disorders.
Atypical antipsychotics, valproate and carbamazepine demonstrated efficacy in a
limited sample of RCTs. LIMITATIONS: The number of RCTs in the treatment of mixed
states is highly limited. Furthermore, nearly all studies were funded by
pharmaceutical companies which may lead to an underestimation of classical mood
stabilizers such as lithium.
PMID- 28417648
TI - Danish translation and validation of Kessler's 10-item psychological distress
scale - K10.
AB - BACKGROUND: Psychological distress is a trans-diagnostic feature of mental
suffering closely associated with mental disorders. Kessler's 10-item
Psychological Distress Scale (K10), a scale with sound psychometric properties,
is widely used in epidemiological studies. AIM: To translate and investigate
whether K10 is a reliable and valid rating scale for the measurement of
psychological distress in a Danish population. METHODS: The translation was
carried out according to official WHO translation guidelines. A sample of 100
subjects was included, 54 patients from the regional Mental Health Service (MHS)
and 46 subjects with no psychiatric history. All participants were assessed with
a psychiatric diagnostic interview (MINI) and handed out K10. Concurrent validity
was assessed by WHO Well-being Index (WHO-5). Correlation matrix analysis was
conducted for the full sample and receiver operating characteristic (ROC) curves
for discriminating mental health service affiliation. RESULTS: Mean K10 scores
differed, with decreasing levels, between inpatients and outpatient in MHS and
the subjects with no psychiatric history. Factor analysis confirmed a
unidimensional structure, and Cronbach's alpha and Omega showed excellent
internal reliability. AUC for the K10 ROC curves showed excellent sensitivity
(0.947 [0.900-0.995]), accurately differentiating mental health from non-mental
health patients. CONCLUSION: The Danish K10 has the same strong internal
reliability as the original English version, and scores differ between
psychiatric patients in outpatient and emergency ward settings. CLINICAL
IMPLICATIONS: The Danish K10 translation is authorized and freely available for
download at https://www.hcp.med.harvard.edu/ncs/k6_scales.php . The utility as an
instrument for clinical screening in a mental healthcare setting is supported.
PMID- 28417649
TI - Internal dysregulation of the renin system in patients with stable liver
cirrhosis.
AB - Sodium retention in cirrhosis is associated with changes in the renin-angiotensin
aldosterone system (RAAS), the sympathetic nervous system (SNS), and the
glomerular filtration rate (GFR). We hypothesized that in cirrhosis the acute
reactions of RAAS and SNS to volume expansion are qualitatively intact, but
occurring from elevated baseline levels. Acute cardiovascular, neurohumoral and
renal responses to central blood volume changes were studied in cirrhotic
patients and healthy controls. In patients, baseline plasma renin concentration
(PRC) was elevated 5-fold compared to controls (p < .001); it increased during
standing (+144%, p < .001) and remained elevated during subsequent sitting
(+118%, p < .001). At baseline, plasma angiotensin II (pANGII) was not elevated
significantly (14 +/- 2 vs. 9 +/- 2 pg/mL) in contrast to plasma aldosterone
(pAldo, +160%, p < .001). During orthostatic RAAS activation, the rise in pAngII
per unit increase in PRC was 0.04 pg AngII/mIU and 0.48 pg AngII/mIU in patients
and controls, respectively (p < .001); similarly, the change in pAldo per unit
change in pANGII was 3.6 in patients and 14.5 pg/pg in controls (p < .001).
Plasma noradrenaline was elevated in the patients, but the dynamic changes were
virtually identical to those of controls. During standing, abrupt decreases in
renal blood flow (-63%, p < .001) and GFR (-42% p < .04) occurred only in
patients. In conclusion, in stable cirrhosis, static and dynamic dysregulation
exists within the RAAS; in the supine position pAngII levels are inappropriately
low, and the AngII-mediated regulation of aldosterone secretion is severely
impeded. In cirrhotic patients, profound reductions in renal blood flow and GFR
occur during standing.
PMID- 28417650
TI - Assessment potential of a new suture simulator in laparoscopic surgical skills
training.
AB - BACKGROUND: The skills necessary for performing effective laparoscopic suturing
are difficult to acquire; as a result, simulators for learning these skills are
rapidly becoming integrated into surgical training. The aim of the study was to
verify whether a new hybrid simulator has the potential to measure skill
improvement in young, less experienced gastroenterological surgeons. MATERIAL AND
METHODS: The study included 12 surgeons (median age, 29 (27-38)] years; 11 men
(91.7%), one woman (8.3%)) who participated in a two-day laparoscopic training
seminar. We used the new simulator before and after the program to evaluate
individual performance. Skills were evaluated using five criteria: volume of air
pressure leakage, number of full-thickness sutures, suture tension, wound area,
and performance time. RESULTS: Air pressure leakage was significantly higher
after than before the training (p = .027). The number of full-thickness sutures
was significantly higher post-training (p < .01). Suture tension was
significantly less post-training (p = .011). Wound opening areas were
significantly smaller post-training (p = .018). Performance time was
significantly shorter post-training (p = .032). CONCLUSIONS: Our study
demonstrated the assessment quality of this new laparoscopic suture simulator.
PMID- 28417651
TI - Laparoscopic management of cholecystoenteric fistula: A single-center experience.
AB - Aim To report our experience regarding management of cholecystoenteric fistula
(CEF) and identify the most effective diagnostic methods and surgical treatment.
Methods In total, 10,588 patients underwent laparoscopic cholecystectomy for
cholecystolithiasis from January 2000 to December 2014 at the Research Institute
of General Surgery, Jinling Hospital (Nanjing, China). Twenty-nine patients were
diagnosed with CEF preoperatively or intraoperatively. Data were retrospectively
collected on demographics, preoperative diagnostics, intraoperative findings,
laparoscopic procedures, complications, and follow-up. Results Twenty-nine
patients (female/male ratio, 2.2; mean age, 68.7 years) with CEF were evaluated.
Twenty-three (79.3%) patients had a cholecystoduodenal fistula (CDF), four
(13.8%) had a cholecystocolonic fistula (CCF), one (3.4%) had a cholecystogastric
fistula, and one (3.4%) had a CDF combined with a CCF. Only nine (31.0%) patients
obtained a preoperative diagnosis. All patients initially underwent laparoscopic
treatment, but five (17.2%) underwent conversion to open surgery; three of these
five developed postoperative morbidity or mortality, and the other two had an
uneventful postoperative course. Among patients managed successfully by
laparoscopy, the hospital stay ranged from 3 to 6 days (mean, 4 days). All
patients were asymptomatic at a mean follow-up of 13 months (range, 3-21 months).
Conclusion Ultrasound and computed tomography can provide valuable diagnostic
clues for CEF. Laparoscopic management of CEF in experienced hands is safe,
feasible, and associated with rapid postoperative recovery.
PMID- 28417652
TI - Modified laparoscopic cholecystectomy technique for treatment of situs inversus
totalis: A case report.
AB - Laparoscopic cholecystectomy is a broadly used technique for gallbladder
treatment. However, situs inversus, a rare anomaly, is reportedly difficult to
treat by conventional laparoscopic cholecystectomy. A 36-year-old woman with
chronic cholecystitis and multiple gallstones was found to have dextrocardia on a
chest X-ray. Magnetic resonance imaging demonstrated situs inversus,
cholecystitis, and cholelithiasis. We successfully performed laparoscopic
cholecystectomy using our modified technique, which mainly involved a left-handed
operation and adjustment of the port positions. This case will be very
instructive for right-handed surgeons in the management of cholelithiasis by
laparoscopic cholecystectomy in patients with situs inversus.
PMID- 28417653
TI - Modified Dufourmentel flap with superior pedicle: a useful technique for
sacrococcygeal pilonidal sinus.
AB - PURPOSE: In order to prevent postoperative infection and recurrence of
sacrococcygeal pilonidal sinus, the authors developed a modified Dufourmentel
flap, involving the superior pedicles, and designed a descriptive prospective
study to evaluate its efficiency. METHODS: Between July 2007 and March 2014, 16
patients with sacrococcygeal pilonidal sinus were treated with an irregular
quadrilateral excision and reconstruction by a modified Dufourmentel flap with
superior pedicle. The duration of wound healing, presence of wound complications
and permanent hypoesthesia, and recurrence rates were recorded and assessed.
RESULTS: None of the patients developed flap necrosis or wound infection
postoperatively. The duration of wound healing was 7.2 +/- 2.9 (range = 6-15)
days. Wound dehiscence was demonstrated in only one patient (6.3%). The mean
follow-up period was 4 years and 2 months (range = 4 months-8 years and 8
months), whereby no permanent hypoesthesia or recurrence was detected.
CONCLUSION: The modified Dufourmentel flap with superior pedicle can be safely
used as a treatment of sacrococcygeal pilonidal sinus, with excellent results.
PMID- 28417654
TI - Assessment of burn size in obese adults; a literature review.
AB - PURPOSE: Obesity causes changes in the total body surface area as well as the
distribution of skin surfaces. In burn management, three methods are commonly
used to determine the surface area burned: the patient's palm, the rule of nines,
and the Lund-Browder chart. These methods rely on the distribution of skin
surface, although none of these methods consider differences in body mass. This
study investigates the relationship between body surfaces and body mass in the
assessment of burn size to determine the validity of the conventional methods
when applied to obese individuals. METHODS: The current literature was reviewed
using relevant electronic databases. The initial search yielded 247 results.
Relevant articles were then reviewed. A total of seven publications fulfilled the
inclusion criteria. RESULTS: The palmar surface area ranged between 0.59%-1.22%,
depending on BMI, gender, and ethnicity, compared to 1% according to conventional
methods. The palmar surface area of obese individuals approximated 0.7% of the
total body surface area in Caucasians. The surface areas comprised 5%-7.5% of the
total body surface area for each arm, 15%-20% for each leg, and 40%-52% for the
trunk in obese or morbidly obese individuals, compared to 9%, 18%, and 36%,
respectively, for normal-weight adults. CONCLUSIONS: The commonly used methods
for assessment of burns should be used with caution when applied to obese burn
patients, and the clinical parameters observed even more systematically.
PMID- 28417655
TI - Dimensionality of the Chinese hospital anxiety depression scale in psychiatric
outpatients: Mokken scale and factor analyses.
AB - OBJECTIVE: The hospital anxiety and depression scale (HADS) is a widely used
scale of anxiety and depression. However, recent studies have challenged the bi
dimensional scoring of the HADS. The present study was to examine the
dimensionality of the Chinese HADS. METHODS: We recruited a convenience sample of
214 adult psychiatric outpatients at a medical centre in Taiwan, and they
completed the Chinese HADS. We used Mokken scale analysis (MSA), exploratory
factor analysis (EFA), exploratory bifactor analysis (EBA) and confirmatory
factor analysis (CFA) to examine the dimensionality of the Chinese HADS. RESULTS:
The Chinese HADS was a moderate Mokken scale (Hs = 0.44), and had a two-factor
structure. EBA showed that one general factor, emotional distress, explained 68%
of the common variance of the Chinese HADS. CFA confirmed that the bifactor model
had the best fit statistics. The items 5 and 7 of the Chinese HADS contributed to
structural ambiguity in the Chinese HADS subscales. CONCLUSIONS: The sum scores
of the Chinese HADS were a reliable and valid unidimensional measure of emotional
distress. The Chinese HADS subscales were incapable of differentiating between
anxiety and depression. Clinicians and researchers should choose other scales
that are specifically designed for measuring anxiety and depression.
PMID- 28417656
TI - In-vivo imaging of meningeal inflammation in multiple sclerosis: Presence of
evidence or evidence of presence?
PMID- 28417657
TI - A "kissing lesion": In-vivo 7T evidence of meningeal inflammation in early
multiple sclerosis.
AB - BACKGROUND: The role of cortical lesions (CLs) in disease progression and
clinical deficits is increasingly recognized in multiple sclerosis (MS); however
the origin of CLs in MS still remains unclear. OBJECTIVE: Here, we report a para
sulcal CL detected two years after diagnosis in a relapsing-remitting MS (RRMS)
patient without manifestation of clinical deficit. METHODS: Ultra-high field (7T)
MR imaging using magnetization-prepared 2 rapid acquisition gradient echoes
(MP2RAGE) sequence was performed. RESULTS: A para-sulcal CL was detected which
showed hypointense rim and iso- to hyperintense core. This was detected in the
proximity of the leptomeninges in the left precentral gyrus extending to the
adjacent postcentral gyrus. CONCLUSION: This finding indicates that inflammatory
infiltration into the cortex through the meninges underlies cortical pathology
already in the early stage of disease and in mild disease course.
PMID- 28417658
TI - Resident Involvement in Professional Otolaryngology Organizations: Current Trends
in the United States.
AB - Involvement by residents in professional medical organizations can enrich their
training, but little data exist regarding the number and types of involvement
opportunities available to otolaryngology residents. We sought to fill this gap
in knowledge by quantifying the extent to which major otolaryngology-related
organizations in the United States provide involvement opportunities to
otolaryngology residents. Our analysis included 23 organizations and subspecialty
societies. Results showed that many opportunities exist for residents to attend
conferences and present research; however, fewer involvement and funding
opportunities existed in any other leadership, health policy, or service-learning
experiences. These findings were consistent across general and subspecialty
societies. Given the many purported benefits of resident involvement in
otolaryngology outside of the standard training environment, future efforts may
be warranted to increase the number and type of involvement opportunities
currently available in professional societies.
PMID- 28417659
TI - Effects of [Nphe1, Arg14, Lys15] N/OFQ-NH2 (UFP-101), a potent NOP receptor
antagonist, on molecular, cellular and behavioural alterations associated with
chronic mild stress.
AB - The present study investigated the effect of [Nphe1] Arg14, Lys15-N/OFQ-NH2 (UFP
101), a selective NOP receptor antagonist, in chronic mild stress (CMS) in male
Wistar rats. NOP receptor antagonists were reported to elicit antidepressant-like
effects in rodents. Our aim was to investigate UFP-101 effects on CMS-induced
anhedonia and impairment of hippocampal neurogenesis. UFP-101 (10 nmol/rat
intracerebroventricularly) did not influence sucrose intake in non-stressed
animals, but reinstated basal sucrose consumption in stressed animals from the
second week of treatment. UFP-101 also reversed stress effects in forced swimming
test and in open field. Fluoxetine (10 mg/kg intraperitoneally) produced similar
effects. Moreover, we investigated whether UFP-101 could affect CMS-induced
impairment in hippocampal cell proliferation and neurogenesis, and in fibroblast
growth factor (FGF-2) expression. Our data confirm that CMS reduced neural stem
cell proliferation and neurogenesis in adult rat hippocampus. Chronic UFP-101
treatment did not affect the reduced proliferation (bromodeoxyuridine-positive
cells) observed in stressed animals. However, UFP-101 increased the number of
doublecortin-positive cells, restoring neurogenesis. Finally, UFP-101
significantly increased FGF-2 expression, reduced by CMS. These findings support
the view that blockade of NOP receptors produces antidepressant-like effects in
CMS associated with positive effects on neurogenesis and FGF-2 expression.
Therefore, NOP receptors may represent a target for innovative antidepressant
drugs.
PMID- 28417660
TI - Anatomic Characteristics, Identification, and Protection of the Nonrecurrent
Laryngeal Nerve during Thyroidectomy.
AB - Objective We aimed to investigate the anatomical features and variation pattern
of the nonrecurrent laryngeal nerve (NRLN), summarize the methods for identifying
the NRLN before and during thyroidectomy, and share experiences regarding
preventing and treating its injury. Study Design Retrospective case data
analysis. Setting First Affiliated Hospital of Harbin Medical University.
Subjects and Methods Between January 2002 and May 2016, 7392 patients underwent
thyroidectomy in our hospital. Of them, 28 patients with NRLN were identified,
and their clinical data were retrospectively analyzed. Results This study
included 7392 patients in which the recurrent laryngeal nerves (RLNs) were
routinely identified during surgery. The presence of NRLN was intraoperatively
confirmed in 28 patients. All the NRLNs were located on the right side and its
overall incidence was 0.37%. Five of the NRLNs were classified as type I, 19 as
type IIa, and 4 as type IIb. Of the 28 cases, 4 NRLNs were injured during
surgery, in which primary end-to-end anastomosis or local seal with
corticosteroid injection was performed as a remedy. In the 4 patients with NRLN
injury, 2 presented with postoperative hoarseness that indicated vocal cord
paralysis confirmed by laryngoscope; the other 2 patients' voices had no
significant changes. Conclusion The NRLN, which is rare in clinical practice and
predominantly right-sided, is anatomically more complex and variant at a higher
risk of surgical injury. The key factors to accurately identify NRLN and to
effectively prevent its injury include careful interpretation of auxiliary
examination results before surgery, raising awareness of its presence, meticulous
dissection, and routine exposure of the RLN during surgery.
PMID- 28417661
TI - Corrective Nasal Surgery after Maxillomandibular Advancement for Obstructive
Sleep Apnea: Experience from 379 Cases.
AB - Objective Efficacy of maxillomandibular advancement (MMA) in the treatment of
obstructive sleep apnea (OSA) is associated with degree of maxillary advancement.
Large maxillary advancement leads to profound changes of the nasolabial region.
We present the incidence and indications of post-MMA corrective nasal surgery in
a large cohort. Study Design Case series with chart review. Setting University
medical center. Subjects and Methods A total of 379 subjects with OSA underwent
MMA at Stanford Hospital (surgeons: S.Y.L., R.W.R.) from August 1992 to December
2015. Data were collected on age, sex, American Society of Anesthesiologists
score, polysomnography parameters, and history of nasal surgery. Primary outcome
parameters were the incidence and indications of post-MMA corrective nasal
surgery. Results Of 379 subjects, the surgical success rate was 76.3% based on
the change in respiratory disturbance index. Seventy-one subjects (18.7%)
underwent corrective nasal surgery after MMA, whereas 48 underwent functional
nasal surgery and 23 underwent both functional and aesthetic nasal surgery. Lower
oxygen saturation nadir and higher baseline respiratory disturbance index were
associated with increased likelihood of post-MMA corrective nasal surgery.
Conclusion MMA surgical success is associated with degree of maxillary
advancement, which is especially significant in patients with severe OSA.
Patients must be counseled on its impact in nasal function and aesthetics. Our
series, the largest to date to address this question, suggests that the incidence
of post-MMA corrective nasal surgery is at least 18.7%. Prospectively, refinement
in MMA techniques is needed to minimize postoperative compromise in nasal form
and function.
PMID- 28417662
TI - Clinician views of patient decisional conflict when deciding between dialysis and
conservative management: Qualitative findings from the PAlliative Care in chronic
Kidney diSease (PACKS) study.
AB - BACKGROUND: Only a paucity of studies have addressed clinician perspectives on
patient decisional conflict, in making complex decisions between dialysis and
conservative management (renal supportive and palliative care). AIM: To explore
clinician views on decisional conflict in patients with end-stage kidney disease.
DESIGN: Interpretive, qualitative study. SETTING AND PARTICIPANTS: As part of the
wider National Institute for Health Research, PAlliative Care in chronic Kidney
diSease study, semi-structured interviews were conducted with clinicians
(nephrologists n = 12; 7 female and clinical nurse specialists n = 15; 15 female)
across 10 renal centres in the United Kingdom. Interviews took place between
April 2015 and October 2016 and a thematic analysis of the interview data was
undertaken. RESULTS: Three major themes with associated subthemes were
identified. The first, 'Frequent changing of mind regarding treatment options',
revealed how patients frequently altered their treatment decisions, some refusing
to make a decision until deterioration occurred. The second theme, 'Obligatory
beneficence', included clinicians helping patients to make informed decisions
where outcomes were uncertain. In weighing up risks and benefits, and the impact
on patients, clinicians sometimes withheld information they thought might cause
concern. Finally, 'Intricacy of the decision' uncovered clinicians' views on the
momentous and brave decision to be made. They also acknowledged the risks
associated with this complex decision in giving prognostic information which
might be inaccurate. LIMITATIONS: Relies on interpretative description which
uncovers constructed truths and does not include interviews with patients.
CONCLUSION: Findings identify decisional conflict in patient decision-making and
a tension between the prerequisite for shared decision-making and current
clinical practice. Clinicians also face conflict when discussing treatment
options due to uncertainty in equipoise between treatments and how much
information should be shared. The findings are likely to resonate across
countries outside the United Kingdom.
PMID- 28417663
TI - Is Neck Dissection Associated with an Increased Risk of Postoperative Stroke?
AB - Objective Prior studies have reported widely disparate rates of postoperative
stroke, with conflicting analyses of whether neck dissection is an independent
risk factor. Study Design Cohort study. Setting American College of Surgeons
National Surgical Quality Improvement Program from 2005 to 2013. Subjects and
Methods We compared the 30-day rate of postoperative stroke between patients
undergoing complete or modified radical neck dissection and a control cohort
composed of those undergoing resections in the oral cavity, oropharynx, larynx,
or hypopharynx without neck dissection. Propensity scores and paired statistics
were used to compare the groups while adjusting for relevant covariates. Results
We identified 9697 patients, including 5827 with neck dissection and 3870 without
neck dissection. In the full cohort, the rate of postoperative stroke was greater
with neck dissection than without it (0.31% vs 0.11%, P = .052), although the
relationship was attenuated by propensity score matching to adjust for
comorbidities (0.30% vs 0.13%, P = .18). Among patients with >=2 risk factors for
carotid artery stenosis, neck dissection was associated with an increased rate of
postoperative stroke (2.68% with bilateral neck dissection, 0.41% with unilateral
neck dissection, and 0.24% without neck dissection, P = .04). The incidence of
stroke was strongly associated with 30-day mortality (7.4% vs 0.2%, P < .001).
Conclusions Stroke is a rare but highly morbid complication after head and neck
surgery. Compared with other head and neck surgery, neck dissection in patients
at risk for carotid artery stenosis is associated with an increased risk of
postoperative stroke.
PMID- 28417664
TI - Low-dose systemic scopolamine disrupts context conditioning in rats.
AB - Cholinergic neurotransmission plays a key role in learning and memory. Prior
research with rats indicated that a low dose of pre-training scopolamine (0.1
mg/kg), a cholinergic receptor antagonist, did not affect cued fear conditioning,
but did block renewal when injected before extinguishing a conditioned tone,
opening up opportunities to pharmacologically improve exposure therapy for
anxiety patients. Before translating these findings to the clinic, it is
important to carefully examine how scopolamine affects contextual fear memories.
Here, we investigated the effects of scopolamine on encoding of contextual
anxiety and its generalization in male Wistar rats. We found a profound
disruption of context conditioning, suggesting that, even at a low dose, systemic
scopolamine may influence contextual encoding in the hippocampus, particularly
when the context is the best predictor for the presence of shocks.
PMID- 28417665
TI - Can Intracapsular Tonsillectomy Be an Alternative to Classical Tonsillectomy? A
Meta-analysis.
AB - Objective Tonsillectomy is the most common operation performed in the
otolaryngologic fields. Efforts have been made to reduce postoperative
complications, and one of these is intracapsular tonsillectomy and adenoidectomy
(ICTA), which leaves the tonsillar tissue with tonsillar capsule. This study
aimed to evaluate intracapsular tonsillectomy compared with classical
extracapsular tonsillectomy in terms of efficacy of the technique for managing
obstructive sleep apnea (OSA) and reducing postoperative complications. Data
Sources We performed a literature search using PubMed, EMBASE, and the Cochrane
Library through December 2016. Review Methods Summarized risk ratio (RR), risk
differences (RDs), and standardized mean differences (SMDs) with 95% confidence
intervals (CIs) were estimated by summarizing the risk estimates of each study
using random-effects models that considered both within- and between-study
variations. Results Our search included 15 randomized controlled studies. The RRs
for postoperative bleeding and residual tonsils were, respectively, 0.44 ( P =
.01) and 6.02 ( P = .0002). There were significant differences in postoperative
pain ( P = .0022), need for analgesics ( P < .0001), days to normal diet ( P =
.006), and days to normal activity ( P < .00001) between intracapsular
tonsillectomy and extracapsular tonsillectomy. Conclusions Intracapsular
tonsillectomy can effectively reduce postoperative pain and bleeding, which
shortens the time required to return to normal life. There was no difference
between microdebrider and coblator in intracapsular tonsillectomy regarding
postoperative pain and bleeding. It can increase the risk of remnant tonsils;
however, it does not increase the risk of recurrent infection.
PMID- 28417666
TI - Exploring the differential associations between components of executive
functioning and reactive and proactive aggression.
AB - OBJECTIVE: A large body of literature confirms the importance of executive
functioning (EF) in the explanation of aggressive and antisocial behaviors.
However, the common and specific associations between subtypes of aggression,
such as reactive (RA), proactive aggression (PA), and EF are unclear. The current
study explored the nuanced associations between components of EF and subtypes of
aggression, using a latent variable approach. METHOD: Participants were 384
racially diverse undergraduate students (ages 18-52 years) who completed a self
report measure of RA and PA, and traditional neuropsychological tasks of EF. The
appropriateness of using a nested bifactor model of EF was confirmed, and this
bifactor model of EF was then used to examine the specific associations between
components of EF and RA and PA. RESULTS: Results revealed that components of EF
are differentially associated with RA and PA. Specifically, impulsive, provoked
aggression (i.e., RA) was associated with lower levels of goal-oriented
inhibition and higher levels of flexibility, whereas planned, goal-oriented
aggression (i.e., PA) was associated with higher levels of working memory.
CONCLUSIONS: Findings from the current study underscore the importance of
considering the multidimensional nature of EF, as well as the heterogeneity
within aggression, rather than considering either construct as a single
monolithic construct. The current study suggests that potentially unique brain
based pathways from aspects of EF to subtypes of aggression may exist, and points
toward potential avenues through which to intervene.
PMID- 28417668
TI - Exploring molecular structural requirement for AChE inhibition through multi
chemometric and dynamics simulation analyses.
AB - The acetylcholinesterase enzyme (AChE) plays an important role in central and
peripheral nervous systems. Acetylcholine (ACh) acts through the regulation of
AChE activity, which can play a key role in accelerating senile amyloid beta
peptide (Abeta) plaque deposition. Therefore, inhibition of the AChE enzyme can
be used as a key principle to prevent ACh depletion. The present study has been
emphasized to explore both ligand- and structure-based 3D QSAR, HQSAR,
pharmacophore, molecular docking and simulation studies on a set of structurally
diverse inhibitors to optimize prime structural features responsible for
selective binding to AChE, and vis-a-vis inhibiting enzyme activity. The
pharmacophore model showed the importance of HB acceptor and donor, positive
ionization and hydrophobic features of the molecule for effective binding.
Structure-based docking and simulation studies adjudged the significance of
features obtained from ligand-based 3D QSAR, CoMFA (Q2 = .608, [Formula: see
text] = .700), CoMSIA (Q2 = .632, [Formula: see text] = .734), HQSAR (Q2 = .850,
[Formula: see text] = .693) and pharmacophore (Q2 = .839, ROCscore = .769)
models. The aim of the present study is to identify the essential structural and
physicochemical profiles of molecules that can provide therapeutic benefits with
less toxicity. Structurally diverse compounds have been used for the study, and
the generated models showed the large applicability domain.
PMID- 28417667
TI - Immediate and short-term biomechanical adaptation of habitual barefoot runners
who start shod running.
AB - This study investigated the immediate and short-term effects of minimalist shoes
(MS) and traditional running shoes (TRS) on vertical loading rates, foot strike
pattern and lower limb kinematics in a group of habitual barefoot runners. Twelve
habitual barefoot runners were randomly given a pair of MS or TRS and were asked
to run with the prescribed shoes for 1 month. Outcome variables were obtained
before, immediate after and 1 month after shoe prescription. Average and
instantaneous vertical loading rates at the 1-month follow-up were significantly
higher than that at the pre-shod session (P < 0.034, eta2p > 0.474). Foot strike
angle in the TRS group was significantly lower than that in the MS group (P =
0.045, eta2p = 0.585). However, there was no significant time nor shoe effect on
overstride, knee and ankle excursion (P > 0.061). Habitual barefoot runners
appeared to land with a greater impact during shod running and they tended to
have a more rearfoot strike pattern while wearing TRS. Lower limb kinematics were
comparable before and after shoe prescription. Longer period of follow-up is
suggested to further investigate the footwear effect on the running biomechanics
in habitual barefoot runners.
PMID- 28417669
TI - Structural basis for the regulation of phytohormone receptors.
AB - Phytohormones are central players in diverse plant physiological events, such as
plant growth, development, and environmental stress and defense responses. The
elucidation of their regulatory mechanisms through phytohormone receptors could
facilitate the generation of transgenic crops with cultivation advantages and the
rational design of growth control chemicals. During the last decade, accumulated
structural data on phytohormone receptors have provided critical insights into
the molecular mechanisms of phytohormone perception and signal transduction.
Here, we review the structural bases of phytohormone recognition and receptor
activation. As a common feature, phytohormones regulate the interaction between
the receptors and their respective target proteins (also called co-receptors) by
two types of regulatory mechanisms, acting as either "molecular glue" or an
"allosteric regulator." However, individual phytohormone receptors adopt specific
structural features that are essential for activation. In addition, recent
studies have focused on the molecular diversity of redundant phytohormone
receptors.
PMID- 28417670
TI - Case-Logging Practices in Otolaryngology Residency Training: National Survey of
Residents and Program Directors.
AB - Objective (1) Evaluate the consistency and manner in which otolaryngology
residents log surgical cases. (2) Assess the extent of instruction and guidance
provided by program directors on case-logging practices. Study Design Cross
sectional national survey. Setting Accreditation Council for Graduate Medical
Education otolaryngology residency programs in the United States. Subjects and
Methods US otolaryngology residents, postgraduate year 2 through graduating
chiefs as of July 2016, were recruited to respond to an anonymous questionnaire
designed to characterize surgical case-logging practices. Program directors of US
otolaryngology residency programs were recruited to respond to an anonymous
questionnaire to elucidate how residents are instructed to log cases. Results A
total of 272 residents and 53 program directors completed the survey, yielding
response rates of 40.6% and 49.5%, respectively. Perceived accuracy of case logs
is low among residents and program directors. Nearly 40% of residents purposely
choose not to log certain cases, and 65.1% of residents underreport cases
performed. More than 80% of program directors advise residents to log procedures
performed outside the operating room, yet only 16% of residents consistently log
such cases. Conclusion Variability in surgical case-logging behaviors and
differences in provided instruction highlight the need for methods to improve
consistency of logging practices. It is imperative to standardize practices
across otolaryngology residency programs for case logs to serve as an accurate
measure of surgical competency. This study provides a foundation for reform
efforts within residency programs and for the Resident Case Log System.
PMID- 28417672
TI - BOOK NOTICES.
PMID- 28417671
TI - The Use of Noninvasive Positive Pressure Ventilation following Pediatric
Tonsillectomy.
AB - Objective To determine the risks of bleeding and other complications in pediatric
patients who require noninvasive positive pressure ventilation (PPV) in the
immediate posttonsillectomy period. Study Design Case series with chart review.
Setting Single tertiary pediatric hospital. Subjects and Methods Sixty-nine
patients who had undergone tonsillectomy from July 2007 through December 2013 and
required postoperative PPV were reviewed. Data collected included age, sex,
medical history, preoperative polysomnogram parameters, length of use and type of
noninvasive ventilatory support, and postoperative complications. Bleeding rate
was calculated. Results Sixty-nine children met inclusion criteria for the study.
Most had comorbid conditions. The mean age of these patients was 6.4 years. The
postoperative bleeding rate of children who required operative intervention for
control was 5.97%. Patients did not experience other complications. Conclusion
This is the largest study in the literature investigating bleeding in pediatric
patients undergoing tonsillectomy who required postoperative noninvasive PPV.
Some hesitation may exist in using this form of ventilation when open pharyngeal
wounds are exposed to pressure, but this study suggests that it can be used as a
suitable alternative to invasive ventilation.
PMID- 28417673
TI - Research progress from the SCI Model Systems (SCIMS): An interactive discussion
on future directions.
AB - CONTEXT/OBJECTIVE: To describe current and future directions in spinal cord
injury (SCI) research. DESIGN: The SCI Model Systems (SCIMS) programs funded by
the National Institute on Disability, Independent Living, and Rehabilitation
Research (NIDILRR) during the 2011 to 2016 cycle provided abstracts describing
findings from current research projects. Discussion among session participants
generated ideas for research opportunities. SETTING/PARTICIPANTS: Pre-conference
workshop before the 2016 American Spinal Injury Association (ASIA) annual
meeting. A steering committee selected by the SCIMS directors that included the
moderators of the sessions at the ASIA pre-conference workshop, researchers
presenting abstracts during the session, and the audience of over 100 attending
participants in the pre-conference workshop. METHODS/RESULTS: Group discussion
followed presentations in 5 thematic areas of (1) Demographics and Measurement;
(2) Functional Training; (3) Psychosocial Considerations; (4) Assistive
Technology; and (5) Secondary Conditions. The steering committee reviewed and
summarized discussion points on future directions for research and made
recommendations for research based on the discussion in each of the five areas.
CONCLUSION: Significant areas in need of research in SCI remain, the goal of
which is continued improvement in the quality of life of individuals with SCI.
PMID- 28417674
TI - International Summit Consensus Statement: Intellectual Disability Inclusion in
National Dementia Plans.
AB - The World Health Organization (WHO) has called for the development and adoption
of national plans or strategies to guide public policy and set goals for
services, supports, and research related to dementia. It called for distinct
populations to be included within national plans, including adults with
intellectual disability (ID). Inclusion of this group is important as having
Down's syndrome is a significant risk factor for early-onset dementia. Adults
with other ID may have specific needs for dementia-related care that, if unmet,
can lead to diminished quality of old age. An International Summit on
Intellectual Disability and Dementia, held in Scotland, reviewed the inclusion of
ID in national plans and recommended that inclusion goes beyond just description
and relevance of ID. Reviews of national plans and reports on dementia show
minimal consideration of ID and the challenges that carers face. The Summit
recommended that persons with ID, as well as family carers, should be included in
consultation processes, and greater advocacy is required from national
organizations on behalf of families, with need for an infrastructure in health
and social care that supports quality care for dementia.
PMID- 28417676
TI - Bio-energy generation in an affordable, single-chamber microbial fuel cell
integrated with adsorption hybrid system: effects of temperature and comparison
study.
AB - : A microbial fuel cell (MFC) integrated with adsorption system (MFC-AHS) is
tested under various operating temperatures with palm oil mill effluent as the
substrate. The optimum operating temperature for such system is found to be at
~35 degrees C with current, power density, internal resistance (Rin), Coulombic
efficiency (CE) and maximum chemical oxygen demand (COD) removal of 2.51 +/- 0.2
mA, 74 +/- 6 mW m-3, 25.4 Omega, 10.65 +/- 0.5% and 93.57 +/- 1.2%, respectively.
Maximum current density increases linearly with temperature at a rate of 0.1772
mA m-2 degrees C-1, whereas maximum power density was in a polynomial function.
The temperature coefficient (Q10) is found to be 1.20 between 15 degrees C and 35
degrees C. Present studies have demonstrated better CE performance when compared
to other MFC-AHSs. Generally, MFC-AHS has demonstrated higher COD removals when
compared to standalone MFC regardless of operating temperatures. ABBREVIATIONS:
ACFF: activated carbon fiber felt; APHA: American Public Health Association; CE:
Coulombic efficiency; COD: chemical oxygen demand; ECG: electrocardiogram; GAC:
granular activated carbon; GFB: graphite fiber brush; MFC: microbial fuel cell;
MFC-AHS: microbial fuel cell integrated with adsorption hybrid system; MFC-GG:
microbial fuel cell integrated with graphite granules; POME: palm oil mill
effluent; PTFE: polytetrafluoroethylene; SEM: scanning electron microscope.
PMID- 28417677
TI - Descriptive Epidemiology of Hypertension and Its Association With Obesity: Based
on the WHO STEPwise Approach to Surveillance in Palau.
AB - The rise of noncommunicable diseases is a serious health burden for Palau. This
study described the prevalence of hypertension, and assessed its association with
obesity. Surveys following the WHO STEPwise approach to surveillance were
conducted in 2529 adults. Multivariate prevalence ratios (PR) of hypertension for
body mass index (BMI) categories were calculated by logistic regression models
using conditional standardization procedure. Age- and sex-specified analyses were
performed. Overall prevalence of obesity and hypertension were 40.4% and 46.8%,
respectively. Prevalence of hypertension was positively associated with BMI.
However, overweight men had as high prevalence of hypertension as the obese
(multivariable-adjusted PR was 1.84 for overweight and 1.91 for obese compared
with nonoverweight). The association between hypertension and BMI was similar
across age groups. The prevalence of hypertension in women increased gradually
with the increase of BMI whereas that in men reached a plateau already in the
overweight.
PMID- 28417678
TI - Changes in peripheral blood T-cell balance after percutaneous tumor ablation.
AB - PURPOSE: To evaluate the changes in T-cell balance in peripheral blood following
percutaneous tumor ablation. MATERIAL AND METHODS: Patients underwent thermal
ablation including radiofrequency (n = 9) and microwave ablation (n = 5), or
cryoablation (n = 5). Target tumors were located in the lung (n = 7), soft tissue
(n = 5), liver (n = 4), and bone (n = 3). Patient peripheral blood samples were
collected before and within 14 days after ablation. Peripheral blood populations
of cytotoxic T-cells (CTL), type-1 (Th1) and type-2 helper T-cells (Th2), and
regulatory T-cells (Treg) were measured using flow cytometry. Changes in CTL/Treg
and Th1/Th2 ratios before and after ablation therapy were compared using paired t
tests. RESULTS: Peripheral blood CTL population (27.5 +/- 2.1% to 30.2 +/- 2.5%,
p < .03) and CTL/Treg ratios (18.8 +/- 3.7% to 21.6 +/- 3.6%, p < .05) increased
significantly after ablation. Although a significant increase in CTL/Treg ratios
was found after heat-based ablation (18.0 +/- 4.4% to 21.6 +/- 4.7%, p < .02), it
remained unchanged after cryoablation (21.0 +/- 7.0% to 21.5 +/- 4.3%, p = .92).
Th1/Th2 ratio (13.7 +/- 3.0% to 17.2 +/- 3.5%, p = .12) remained unchanged after
ablation. CONCLUSION: Ablation therapy alters the T-cell balance by increasing
the systemic CTL/Treg, ratio. Heat-based ablation might be a more effective
approach than cryoablation to enhance systemic anti-tumor immunity.
PMID- 28417679
TI - Synergy or interference of a H9N2 avian influenza virus with a velogenic
Newcastle disease virus in chickens is dose dependent.
AB - Field observations indicate that the impact of velogenic Newcastle disease virus
(vNDV) is more severe in countries with concomitant circulation of low
pathogenicity avian influenza virus, as is the case in the Middle East, in
particular in Israel, where H9N2 and NDV are endemic. In our study, we evaluated
how the exposure of chickens to an H9N2 challenge either favours or interferes
with a subsequent vNDV infection and its transmission to sentinels. For this
purpose, single vNDV and sequential H9/NDV challenges were performed with
increasing doses of vNDV (101-106 EID50). The H9N2 challenge made birds more
susceptible to the vNDV, lowering the minimum dose required to cause an
infection, exacerbating the clinical outcome, while delaying the onset of the
disease and time of death. Interestingly, the presence and degree of these
seemingly contrasting effects were dose-dependent and not mutually exclusive.
PMID- 28417680
TI - Designing medical internships to improve recruitment and retention of doctors in
rural areas.
AB - BACKGROUND: The medical internship as a way of exposing young doctors to training
in a rural context is regarded as a useful tool to recruit and retain doctors in
rural areas. Norwegian health authorities tested an arrangement of early sign-up
for medical internships in the Finnmark County in Norway. OBJECTIVE: To report on
the effects of the early sign-up for medical internship. DESIGN: This study
compares the choice of workplace after internship among physicians who signed up
early with those candidates assigned to the raffle model of internship in the
study area, and in a comparison area experiencing similar recruitment and
retention problems. RESULTS: The proportion of interns who signed up early that
still worked as physicians in the study area by April 2014 (29%) was twice as
high as among the regular interns (15%) and interns in the comparison area (14%).
Among the 59 interns who signed up early still working in the study area in April
2014, 33% had grown up in this area. However, the greatest benefits were for the
most densely populated municipalities in the study area. CONCLUSIONS: The early
sign-up model had a net contribution of proving additional physicians in the
study area.
PMID- 28417681
TI - Proximal femoral nail antirotation versus dynamic hip screw fixation for
treatment of osteoporotic type 31-A1 intertrochanteric femoral fractures in
elderly patients.
AB - Objective To evaluate long-term radiographic and functional outcomes between
dynamic hip screw (DHS) and proximal femoral nail antirotation (PFNA) fixation
for treatment of osteoporotic type 31-A1 intertrochanteric femoral fractures
(IFFs) among elderly patients Methods A retrospective comparative study was
carried out. Follow-up was performed at 1, 3, 6, 9, and 12 months postoperatively
and yearly thereafter. The primary outcome was the radiographic outcome, and the
secondary outcome was the functional outcome. Results A significant difference in
radiographic complications was observed between the DHS group (n = 45, 40.2%) and
PFNA group (n = 15, 13.6%). The risk of femoral shaft fracture after implant
removal at the 1-year follow-up was increased by 0.9% (n = 1) and 6.3% (n = 7) in
the PFNA and DHS groups, respectively. This difference persisted with rates of
3.6% (n = 4) and 12.5% (n = 14) at the final follow-up. Additionally, significant
differences were present in the Harris hip score at each visit. Conclusion Our
results indicate that PFNA yields better outcomes than DHS fixation among elderly
patients with osteoporotic type 31-A1 IFFs.
PMID- 28417682
TI - Does Social Support Buffer the Association Between Stress Eating and Weight Gain
During the Transition to College? Differences by Gender.
AB - This study sought to examine whether social support moderates the relationship
between stress eating and body mass index (BMI) change over the freshman year in
males and females. This longitudinal study included 70 college students (72.9%
female; M age = 18.23) who completed self-reported measures of stress eating and
perceived social support, with objective height and weight measurements
collected. Among males, social support moderated the relationship between stress
eating and BMI change. Among males, social support may serve as a buffer against
the impact of stress eating on weight gain during the freshman year of college.
PMID- 28417683
TI - Tracheostomy for Severe Pediatric Obstructive Sleep Apnea: Indications and
Outcomes.
AB - Objectives (1) To describe characteristics of pediatric patients undergoing
tracheostomy for obstructive sleep apnea (OSA). (2) To highlight perioperative
events and outcomes of the procedure. Study Design Case series with chart review.
Setting Four tertiary care academic children's hospitals. Subjects and Methods
Twenty-nine children aged <18 years from January 1, 2010, to December 31, 2015,
who underwent tracheostomy for severe OSA, defined as an apnea-hypopnea index
(AHI) >10, were included in the study. Data on patient characteristics,
polysomnographic findings, comorbidities, and perioperative events and outcomes
were collected and analyzed. Results Twenty-nine patients were included. Mean age
at tracheostomy was 2.0 years (95% CI, -2.2 to 6.2). Mean body mass index z score
was -1.2 (95% CI, -4.9 to -2.5). Mean preoperative AHI was 60.2 (95% CI, -15.7 to
136.1). Mean postoperative intensive care unit stay was 23.2 days (95% CI, 1.44
45.0). One procedure was complicated by bronchospasm. Thirteen patients had
craniofacial abnormalities; 10 had a neurologic disorder resulting in hypotonia;
and 5 had a diagnosis of laryngomalacia. Mean follow-up was 30.6 months (95% CI,
10.4 to 71.6). Six patients were decannulated, with a mean time to decannulation
of 40.8 months (95% CI, 7.9-73.7). Five patients underwent capped sleep study
prior to decannulation with a mean AHI of 6.6 (95% CI, -9.9 to 23.1) and a mean
oxygen nadir of 90.0% (95% CI, 80%-100%). Conclusion OSA is an uncommon
indication for tracheostomy in children. Patients who require the procedure
usually have an associated syndromic diagnosis resulting in upper airway
obstruction. The majority of children who undergo tracheostomy for OSA will
remain dependent at 24 months.
PMID- 28417685
TI - Independent socio-demographic and clinical correlates associated with the
perception of quality of life of women with postpartum depressionin North
central, Nigeria.
AB - OBJECTIVE: Quality of life (QoL) is probably the most desired outcome of all
health care policies and monitoring. This concept is seldom used on women in the
postpartum, especially in the developing world. AIM: This study aimed at
determining the independent socio-clinical variables associated with the
perception of QoL of women with postpartum depression. METHODS: A two-stage cross
sectional procedure was used to recruit 550 participants, out of whom 531
participants completed the questionnaires with 116 participants found to have
postpartum depression and were the studied population, in Nigeria. The Socio
demographic questionnaire, the Edinburgh Postnatal Depression Scale, the World
Health Organization Quality of Life-Bref-26 and the Depression Module of the
Structured Clinical Interview for DSM-IV axis I Diagnosis were used. RESULTS:
Participants with postpartum depression had significantly poor perception of QoL
in all the four domains of the WHOQoL-BREF-26. The independent socio-demographic
and clinical correlate associated with poor perception for both rating of QoL and
satisfaction with health was education (beta = 0.321, p < .001 and beta = 0.0326,
p = .002, respectively); for physical domain [(modes of delivery) (beta = -0.28,
p = .016)]; psychological domain [(age <35years) (beta = 0.391, p = .010)] and
for social relationships [(complications during delivery) (beta = 0.257, p =
.043)]. CONCLUSIONS: The determination of the predictors of QoL, which is an
indicator of disease outcome will improve service delivery to women of
childbearing age.
PMID- 28417686
TI - Trauma epidemiology in Puerto Rico: in-hospital morbidity and mortality from 2002
to 2011.
AB - This study aimed to describe the distribution of injury mechanisms and to assess
the impact of those mechanisms on the morbidity and mortality of trauma. All
patients admitted to Puerto Rico Trauma Hospital (2002-2011) for road-traffic
collisions (RTCs, 5,371), gunshot wounds (GSWs, 2,946), falls (2,319), pedestrian
accidents (1,652), and stab wounds (SWs, 1,073) were selected. Gunshot victims
were 1.19 (95%CI: 1.07-1.33) times as likely as road-traffic victims to have an
ISS >=25. Pedestrians were 1.76 (95%CI: 1.49-2.09) times more likely to have a
GCS <=8 than road-traffic victims were. The risk of dying was 2.64 (95%CI: 2.20
3.16) times higher for gunshot victims and 1.51 (95%CI: 1.23-1.86) times higher
for pedestrians compared to patients who had had RTCs. Gunshot victims and
pedestrians had the worst clinical outcomes. Accordingly, these patients should
receive the most aggressive clinical management. Furthermore, it is imperative to
develop public health campaigns on trauma prevention.
PMID- 28417687
TI - Does a perceptuomotor skills assessment have added value to detect talent for
table tennis in primary school children?
AB - Talent detection intends to support lifelong sports participation, reduce
dropouts and stimulate sports at the elite level. For this purpose it is
important to reveal the specific profile which directs children to the sports
that connect to their strengths and preferences. This study evaluated a
perceptuomotor skills assessment as part of talent detection for table tennis, a
sport in which perceptuomotor skills are considered essential to cope with the
difficult technical aspects. Primary school children (n = 121) and gifted young
table tennis players (n = 146) were assessed using the Dutch perceptuomotor
skills assessment measuring "ball control" and "gross motor function". A
discriminant function analysis confirmed the added value by identifying primary
school children fitting the table tennis perceptuomotor profile of the young
gifted table tennis players (28%). General linear model analyses for the
assessment's individual test items showed that the table tennis players
outperformed their primary school peers on all "ball control" items (P < 0.001).
In conclusion, the assessment appears to be of added value for talent detection
in table tennis at this young age. Longitudinal studies need to reveal the
predictive value for sports participation and elite sports.
PMID- 28417688
TI - Medical professionalism frameworks across non-Western cultures: A narrative
overview.
AB - BACKGROUND: Medical professionalism is context-specific, but most literature on
professionalism stems from Western countries. This study is about benchmarking of
different frameworks on professionalism and interpreting the commonalities and
discrepancies of understanding professionalism across different cultures. We need
to study the cultural underpinning of medical professionalism to graduate future
"global" practitioners who are culturally sensitive enough to recognize
differences (and also similarities) of expectations of patients in various
contexts. AIM: This study aims at describing culture specific elements of three
identified non-Western frameworks of professionalism, as well as their
commonalities and differences. METHOD: A narrative overview was carried out of
studies that address professionalism in non-Western cultures in the period 2002
2014. RESULTS: Out of 143 articles on medical professionalism, only four studies
provided three structured professionalism frameworks in non-Western contexts.
Medical professionalism attributes in non-Western cultures were influenced by
cultural values. Out of the 24 identified attributes of professionalism, 3
attributes were shared by the three cultures. Twelve attributes were shared by at
least two cultures, and the rest of the attributes were unique to each culture.
CONCLUSIONS: The three frameworks provided culture-specific elements in a unique
conceptual framework of medical professionalism according to the region they
originated from. There is no single framework on professionalism that can be
globally acknowledged. A culture-oriented concept of professionalism is necessary
to understand what the profession is dedicated to and to incorporate the concept
into the medical students' and physicians' professional identity formation.
PMID- 28417684
TI - Toward a multiscale modeling framework for understanding serotonergic function.
AB - Despite its importance in regulating emotion and mental wellbeing, the complex
structure and function of the serotonergic system present formidable challenges
toward understanding its mechanisms. In this paper, we review studies
investigating the interactions between serotonergic and related brain systems and
their behavior at multiple scales, with a focus on biologically-based
computational modeling. We first discuss serotonergic intracellular signaling and
neuronal excitability, followed by neuronal circuit and systems levels. At each
level of organization, we will discuss the experimental work accompanied by
related computational modeling work. We then suggest that a multiscale modeling
approach that integrates the various levels of neurobiological organization could
potentially transform the way we understand the complex functions associated with
serotonin.
PMID- 28417689
TI - A Bayesian hierarchical model for discrete choice data in health care.
AB - In discrete choice experiments, patients are presented with sets of health states
described by various attributes and asked to make choices from among them.
Discrete choice experiments allow health care researchers to study the
preferences of individual patients by eliciting trade-offs between different
aspects of health-related quality of life. However, many discrete choice
experiments yield data with incomplete ranking information and sparsity due to
the limited number of choice sets presented to each patient, making it
challenging to estimate patient preferences. Moreover, methods to identify
outliers in discrete choice data are lacking. We develop a Bayesian hierarchical
random effects rank-ordered multinomial logit model for discrete choice data.
Missing ranks are accounted for by marginalizing over all possible permutations
of unranked alternatives to estimate individual patient preferences, which are
modeled as a function of patient covariates. We provide a Bayesian version of
relative attribute importance, and adapt the use of the conditional predictive
ordinate to identify outlying choice sets and outlying individuals with unusual
preferences compared to the population. The model is applied to data from a study
using a discrete choice experiment to estimate individual patient preferences for
health states related to prostate cancer treatment.
PMID- 28417690
TI - Global scientific production in the field of knee arthroplasty: A cross-sectional
survey of research activities.
AB - Objective To determine the quantity and quality of articles in the field of knee
arthroplasty worldwide and elucidate the characteristics of global scientific
production. Methods Web of Science was used to identify articles in the field of
knee arthroplasty from 2011 to 2015. The total number of papers, number of papers
per capita, total number of citations, and mean number of citations were
collected. Results In total, 11,590 papers were identified. The number of
publications significantly increased from 2011 to 2015. Most originated from
North America, East Asia, and West Europe. Most (88.51%) were from high-income
countries, 11.48% were from middle-income countries, and only 0.01% were from
lower-income countries. The United States had the most articles and total
citations. Sweden had the highest mean citations, followed by Denmark and Canada.
However, when adjusted by population size, Denmark had the most articles per
million population, followed by Switzerland and the Netherlands. Conclusions The
number of knee arthroplasty publications has rapidly increased in recent years.
The United States is the most prolific, but some European countries are more
productive relative to their population.
PMID- 28417691
TI - Telangiectasias in Osler-Weber-Rendu Syndrome.
PMID- 28417692
TI - Autobiographical remembering regulates emotions: a functional perspective.
AB - Emotional deviation has been considered an essential factor in emotion
regulation, in that, attempts to compensate for the deviation is reflected on
cognitive processes. In the present study, we focused on autobiographical
remembering and tested the functional role of memory on emotion regulation. We
specifically examined the congruence effect in individuals' subsequent memory
reports after recalling emotional events. Individuals were randomly assigned to
three groups to report either sadness or anger evoking events or emotionally
unspecified events that they experienced in the last five years. Results
supported mood-incongruence, but only for the emotional memory groups. Despite
highly negative memories reported in the initial recall, individuals in anger-
and sad-memory groups revealed an up-regulation trend in subsequent recall.
Furthermore, sadness and anger induction affected phenomenological features of
the subsequently reported memory. Overall, our findings supported for the emotion
regulation function of remembering that serves counter-regulation of the negative
emotion. We discuss potential mechanisms in the light of explanations by a
functional approach to autobiographical memory.
PMID- 28417694
TI - Association between environmental contaminants and health outcomes in indigenous
populations of the Circumpolar North.
AB - Background Since the 1990s, research has been carried out to monitor
environmental contaminants and their effects on human health in the Arctic.
Although evidence shows that Arctic indigenous peoples are exposed to higher
levels of contaminants and do worse on several dimensions of health compared with
other populations, the contribution of such exposures on adverse outcomes is
unclear. Objective The purpose of this review is to provide a synopsis of the
published epidemiological literature that has examined association between
environmental contaminants and health outcomes in Arctic indigenous populations.
Design A literature search was conducted in OVID Medline (1946-January 2014)
using search terms that combined concepts of contaminant and indigenous
populations in the Arctic. No language or date restrictions were applied. The
reference lists of review articles were hand-searched. Results Of 559 citations,
60 studies were relevant. The studies fell under the following categories:
paediatric (n=18), reproductive health (n=18), obstetrics and gynaecology (n=9),
cardiology (n=7), bone health (n=2), oncology (n=2), endocrinology (n=2) and
other (n=2). All studies, except one from Arctic Finland, were either from
Nunavik or Greenland. Most studies assessed polychlorinated biphenyls (n=43) and
organochlorine pesticides (n=29). Fewer studies examined heavy metals,
perfluorinated compounds, or polybrominated diphenyl ethers. Details of study
results for each health category are provided. Conclusions It is difficult to
make conclusive statements about the effects of environmental contaminants on
health due to mixed results, small number of studies and studies being restricted
to a small number of regions. Meta-analytical synthesis of the evidence should be
considered for priority contaminants and health outcomes. The following research
gaps should be addressed in future studies: association of contaminants and
health in other Arctic regions (i.e. Inuvialuit Settlement Region, Nunavut,
Nunatsiavut, Alaska, European North and Russian North); assessment of
contaminants on chronic diseases; inclusion of clinical endpoints in assessments;
and assessment of the emerging contaminants of perfluorinated compounds and
polybrominated diphenyl ethers.
PMID- 28417695
TI - A mixed methods inquiry into the determinants of traditional food consumption
among three Cree communities of Eeyou Istchee from an ecological perspective.
AB - Background The Aboriginal nations of Canada have higher incidences of chronic
diseases, coinciding with profound changes in their environment, lifestyle and
diet. Traditional foods can protect against the risks of chronic disease.
However, their consumption is in decline, and little is known about the complex
mechanisms underlying this trend. Objective To identify the factors involved in
traditional food consumption by Cree Aboriginal people living in 3 communities in
northern Quebec, Canada. Design A mixed methods explanatory design, including
focus group interviews to interpret the results of logistic regression. Methods
This study includes a secondary data analysis of a cross-sectional survey of 3
Cree communities (n=374) and 4 focus group interviews (n=23). In the first,
quantitative phase of the study, data were collected using a food-frequency
questionnaire along with a structured questionnaire. Subsequently, the focus
group interviews helped explain and build on the results of logistic regressions.
Results People who consume traditional food 3 days or more weekly were more
likely to be 40 years old and over, to walk 30 minutes or more per day, not to
have completed their schooling, to live in Mistissini and to be a hunter (p<0.05
for all comparisons). The focus group participants provided explanations for the
quantitative analysis results or completed them. For example, although no
statistical association was found, focus group participants believed that
employment acts as both a facilitator and a barrier to traditional food
consumption, rendering the effect undetectable. In addition, focus group
participants suggested that traditional food consumption is the result of
multiple interconnected influences, including individual, family, community and
environmental influences, rather than a single factor. Conclusions This study
sheds light on a number of factors that are unique to traditional foods, factors
that have been understudied to date. Efforts to promote and maintain traditional
food consumption could improve the overall health and wellbeing of Cree
communities.
PMID- 28417696
TI - BOOK NOTICES.
PMID- 28417697
TI - Case-control study of breast cancer and exposure to synthetic environmental
chemicals among Alaska Native women.
AB - Background Exposure to environmental chemicals may impair endocrine system
function. Alaska Native (AN) women may be at higher risk of exposure to these
endocrine disrupting chemicals, which may contribute to breast cancer in this
population. Objective To measure the association between exposure to select
environmental chemicals and breast cancer among AN women. Design A case-control
study of 170 women (75 cases, 95 controls) recruited from the AN Medical Center
from 1999 to 2002. Participants provided urine and serum samples. Serum was
analyzed for 9 persistent pesticides, 34 polychlorinated biphenyl (PCB)
congeners, and 8 polybrominated diethyl ether (PBDE) congeners. Urine was
analyzed for 10 phthalate metabolites. We calculated geometric means (GM) and
compared cases and controls using logistic regression. Results Serum
concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB
153, PCB-180) were lower in case women than controls. BDE-47 was significantly
higher in case women (GM=38.8 ng/g lipid) than controls (GM=25.1 ng/g lipid)
(p=0.04). Persistent pesticides, PCBs, and most phthalate metabolites were not
associated with case status in univariate logistic regression. The odds of being
a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP)
concentrations that were above the median; this relationship was seen in both
univariate (OR 2.16, 95% CI 1.16-4.05, p=0.02) and multivariable (OR 2.43, 95% CI
1.13-5.25, p=0.02) logistic regression. Women with oestrogen receptor (ER)
/progesterone receptor (PR)-tumour types tended to have higher concentrations of
persistent pesticides than did ER+/PR+ women, although these differences were not
statistically significant. Conclusions Exposure to the parent compound of the
phthalate metabolite MEHP may be associated with breast cancer. However, our
study is limited by small sample size and an inability to control for the
confounding effects of body mass index. The association between BDE-47 and breast
cancer warrants further investigation.
PMID- 28417698
TI - Vitamin D status of northern indigenous people of Russia leading traditional and
"modernized" way of life.
AB - Background Vitamin D status in groups of northern indigenous people of Russia
leading close to traditional (seminomadic reindeer herding), post-traditional (in
settlements) or "modernized" (in towns) way of life was analysed. Design The
survey study groups consisted of 178 Nenets and Komi aged 18-60 living in the
Arctic (66-67 degrees N). Urban Komi, Udmurts and Komi-Permiaks (n=150) living in
a non-Arctic area (57-61 degrees N) formed a control group. The concentration of
serum 25-hydroxyvitamin D (25OHD), as a transport form of vitamin D, was assessed
by enzyme immunoassay analysis. Results The group average 25OHD levels in both
rural and urban Arctic residents are within the range of values seen in the non
Arctic urban subjects adjusted for season: 39.7-47.7 nmol/l. Abandoning
traditional lifestyle associates with lower vitamin D levels in indigenous Arctic
people. Mean+/-standard deviation 25OHD values among Nenets were lower in those
living in the administrative centre (a big settlement) with a population of 1,460
(32.2+/-12.90 nmol/l) than in the residents of small settlements (39.6+/-14.08
nmol/l), and in reindeer herders (42.4+/-13.45 nmol/l; p<0.05 in both cases).
Komi townspeople had lower 25OHD concentrations (47.7+/-12.00 nmol/l) than Komi
reindeer herders (68.7+/-25.20; p<0.01). Conclusions The transition from
seminomadic to post-traditional and "modernized" way of life has led to a
decrease in the consumption of traditional foods among the indigenous people of
the Russian Arctic. Our data support the notion that the traditional northern
diet promotes healthy vitamin D levels, while adherence to the "western" type of
diet correlates with a lower 25OHD concentration.
PMID- 28417700
TI - Editorial - the state of the journal.
PMID- 28417699
TI - Periodontal status among patients with diabetes in Nuuk, Greenland.
AB - Background Diabetes is becoming more common in the Greenlandic population.
Patients with diabetes are more prone to periodontal disease. Periodontal status
may have an effect on metabolic control. Objective The aim of this study was to
estimate the prevalence of periodontitis amongst patients with diabetes in Nuuk,
Greenland, and secondly, to observe if dental care was associated with improved
periodontal status and metabolic control. Study design Observational cross
sectional study and a pilot study of a dental care intervention. Methods Sixty
two Greenlandic patients with diabetes were included in the study. Data were
collected from the Electronic Medical Records (EMR), in addition to a telephone
interview. Patients were offered 3 dental examinations with a 3-month interval.
The dental examinations consisted of a full-mouth assessment of number of
remaining teeth and assessment of periodontal status. Patients received scaling
and root planing, together with information and instructions on oral hygiene.
Information on glycated haemoglobin (HbA1C) values was collected from the EMR at
each dental examination. Results In this study, 21.0% (13/62) of patients with
diabetes had periodontitis. About 42% had less than 20 teeth. The association
between diabetes and periodontitis was known by 20 out of the 62 patients. Over
half of the patients had been to a dental examination within the last year. The
prevalence of periodontitis decreased significantly from 21.0 to 0% (p<0.001)
after 3 dental examinations. No change in HbA1C levels was observed (p=0.440).
Conclusion Periodontitis was common among patients with diabetes in Nuuk. Dental
health status based on Periodontal Screening Index (PSI) and bleeding on probing
(BOP) seemed to improve after dental health care, indicating a need for increased
awareness among patients and health care professionals. HbA1C levels were not
improved among the patients.
PMID- 28417701
TI - Survey of hand surgeons' and therapists' perceptions of the benefit of common
surgical procedures of the hand.
AB - OBJECTIVE: The objectives of this survey were (1) to study if surgeons'
perceptions of the benefit of six surgical procedures differ if they consider
themselves as patients instead of treating a patient, (2) to evaluate the role of
five predetermined factors that may influence decision-making, and (3) to assess
how uniformly hand surgeons and hand therapists perceive the benefits of the
surgical treatments. METHODS: The members of the national societies for Hand
Surgery and Hand Therapy were asked to participate in the survey. Six patient
cases with hand complaint (carpal tunnel syndrome, flexor tendon injury, dorsal
wrist ganglion, thumb amputation, boxer's fracture, and mallet fracture) and a
proposed operative procedure were presented, and the respondents rated the
procedures in terms of the expected benefit. Half of the surgeons were advised to
consider themselves as patients when filling out the survey. RESULTS: A survey
was completed by 56 surgeons (61%) and 59 therapists (20%). Surgeons who
considered themselves as patients had less confident perception on the benefit of
carpal tunnel release compared with surgeons, who considered treating patients.
Hand surgeons and hand therapists had similar perception of the benefits of
surgery. The expected functional result was regarded as the most important factor
in directing the decision about the treatment. CONCLUSIONS: Surgeons tended to be
more unanimous in their opinions in cases, where there is limited evidence on
treatment effect. The agreement between surgeons and therapists implies that the
clinical perspectives are similar, and probably reflect the reality well.
PMID- 28417702
TI - Quinolone resistance-associated amino acid substitutions affect enzymatic
activity of Mycobacterium leprae DNA gyrase.
AB - Quinolones are important antimicrobials for treatment of leprosy, a chronic
infectious disease caused by Mycobacterium leprae. Although it is well known that
mutations in DNA gyrase are responsible for quinolone resistance, the effect of
those mutations on the enzymatic activity is yet to be studied in depth. Hence,
we conducted in vitro assays to observe supercoiling reactions of wild type and
mutated M. leprae DNA gyrases. DNA gyrase with amino acid substitution Ala91Val
possessed the highest activity among the mutants. DNA gyrase with Gly89Cys showed
the lowest level of activity despite being found in clinical strains, but it
supercoiled DNA like the wild type does if applied at a sufficient concentration.
In addition, patterns of time-dependent conversion from relaxed circular DNA into
supercoiled DNA by DNA gyrases with clinically unreported Asp95Gly and Asp95Asn
were observed to be distinct from those by the other DNA gyrases.
PMID- 28417703
TI - Central pedicle reduction mammaplasty with a vertical scar: a technical
modification.
AB - BACKGROUND: This study introduces a central pedicle reduction mammaplasty with a
vertical scar technique. OBJECTIVES: This study is aimed to create a more conical
breast shape and long-lasting better projection by modifying reduction
mammaplasty by central pedicle flap. METHOD: Preoperative markings were made
including the meridian line of breast and the new location of the nipple-areola
complex (NAC). The new location of the inframammary fold was marked ~2 ~ 4 cm
above the original inframammary fold. An incision was made around the areola, the
area between the resection margins and NAC was excised en bloc. The breast
parenchyma was excised circumferentially, so that a cone shaped central mound was
formed. An inferior and inferolateral glandular resection was performed to reduce
the area of the breast base by elevating the position of the inframammary fold.
After completion of dissection, the central pedicle surmounted by the NAC was
transposed to its new location. RESULT: Fifty-six patients were operated with our
modified central pedicle technique. The mean amount of resection was 475 g (range
= 130-1080 g). The mean length of follow-up was 18 months (range = 12-53 months).
The mean postoperative satisfaction score was 4.23 (SD = 0.81). The breast
parenchymal ratio significantly increased from 1.2 preoperatively to 3.9
postoperatively. CONCLUSION: The modified central pedicle reduction mammaplasty
with a vertical scar technique is a versatile breast reduction technique for all
shapes and tissue conditions, by providing an attractive conical shape of the
breast with minimum scar burden and maximum preservation of breast function.
PMID- 28417704
TI - Effects of Silver Nitrate Cauterization on Middle Turbinate Synechia after
Endoscopic Sinus Surgery.
AB - Objective This study aimed to examine the efficacy of silver nitrate
cauterization of the middle turbinate (MT) for hindering postoperative middle
meatal synechia formation after endoscopic sinus surgery (ESS). Study Design
Prospective, controlled, and single-blinded. Settings Tertiary referral center.
Subjects and Methods For this study, 38 patients undergoing bilateral ESS due to
nasal polyposis were recruited. Following ESS, silver nitrate cauterization of
the lateral side of the left MT was performed in all cases. The noncauterized
opposite right sides served as controls. All patients received the standard ESS
protocol, intraoperative middle meatal packing, and postoperative management. The
main outcome measured was the formation of partial or complete MT synechia at the
end of 6-month assessment, performed by a blinded observer. Results At the end of
the 6-month follow-up period, MT synechia formation was observed in 7 of the
right sides (7 of 38, 18.4%) and none in any left sides. The rate of synechia
formation was significantly higher in the controls when compared with the silver
nitrate-cauterized sides ( P < .001). Conclusion The results of this study
suggest that silver nitrate cauterization of the MT is a practical and efficient
method to eliminate middle meatal synechia after ESS.
PMID- 28417707
TI - Report from the Secretaries General of the Royal Belgian Society for Surgery The
Next Step.
PMID- 28417705
TI - Degradation of staphylococcal enterotoxin A by a Pseudomonas aeruginosa isolate
from raw milk.
AB - Recently, we found that staphylococcal enterotoxin A (SEA)-producing
Staphylococcus aureus strains produced SEA in raw milk with microbial
contaminants at high temperatures like 40 degrees C only. Moreover, the
concentration of SEA produced in raw milk gradually decreased after the peak. The
reason(s) for SEA degradation in raw milk was studied in this study. Degradation
of SEA spiked in raw milk was observed at 40 degrees C, but not at 25 degrees
C. A Pseudomonas aeruginosa isolate from raw milk degraded SEA spiked in broth at
40 degrees C. A sample partially purified with a chromatographic method from
culture supernatant of the isolate degraded SEA. Two main proteolytic bands were
observed in the sample by zymographic analysis with casein. These results
suggested that the SEA in raw milk might be degraded by a protease(s) produced by
the P. aeruginosa isolate. This finding might be the first report on SEA
degradation by a proteolytic enzyme(s) derived from Pseudomonas bacteria to our
knowledge.
PMID- 28417713
TI - Caring about the quality of surgical care in Belgium ? Why and how Opening
lecture of the 5th Belgian Surgical Week.
PMID- 28417718
TI - Occurrence of pancreatic, biliary tract, and gallbladder cancers in Alaska Native
people, 1973-2007.
AB - OBJECTIVES: To describe the occurrence of pancreatic, biliary tract, and
gallbladder cancers within the Alaska Native (AN) population. STUDY DESIGN:
Population-based analysis utilizing a tumor registry and comparative population
data. METHODS: Pancreaticobiliary cancers rates for AN people during 1973-2007
were determined from the Surveillance, Epidemiology, and End Results (SEER) AN
Tumor Registry. Cancer incidence rates were age-adjusted to the World Standard
Million and compared over 2 time periods with US white and black rates. RESULTS:
During 1973-2007, 213 AN people developed pancreatic cancer, 73 gallbladder
cancer and 61 biliary tract cancer. Pancreatic cancer occurs at similar rates in
AN men and women, but data for 1993-2007 indicate that the rates among AN men may
be increasing. The incidence rate in AN women (9.5/100,000) was statistically
higher than in US white women (5.8/100,000). The incidence for biliary tract
cancer in AN men and gallbladder cancer in AN men and women is statistically
higher than that for US whites and blacks. CONCLUSIONS: Pancreaticobiliary
cancers, particularly biliary tract and gallbladder cancers, in both AN men and
women and pancreatic cancer in women occur at an increased rate in AN people.
Risk factors relating to the elevated rate are discussed. Certain factors are
potentially modifiable, such as the use of tobacco and obesity.
PMID- 28417719
TI - Translational research to reduce trans-fat intakes in Northern Quebec (Nunavik)
Inuit communities: a success story?
AB - Following our results, based on population studies conducted in Greenland and
Northern Canada, that Nunavik Inuit were thrice as highly exposed to dietary
trans-fat as were Greenlandic Inuit, and that the biological levels found in
Nunavik were already associated with deleterious blood lipid profiles, we decided
to engage in translational activities. Our goal was to support Inuit communities
in the practical implementation of a reduction of the trans-fat content of food
sold in Nunavik. We carried out a preliminary feasibility study in Kuujjuaq and
participated in several meetings. This translational phase involved an Inuk
leader, an Inuk student, a southern student, a southern nutritionist and a
southern researcher in the framework of a public health project. In the present
article, we recount the different phases of the process, from research
implementation to results dissemination and institutional commitment to implement
a primary prevention program of reduction in trans-fat exposure in Nunavik. This
is the occasion to draw broader conclusions on the factors that could either act
in favour of or, on the contrary, would likely compromise the implementation of
primary prevention interventions dealing with food and nutrition in the Arctic.
Finally, we share some reflections on future translational activities dealing
with trans-fat as well as other junk food issues. The analytical framework we
propose integrates a range of factors, from geo-climatic to socio-economic, ethno
cultural, and even political, that we think should be examined while identifying
and building preventive recommendations and strategies related to the Northern
diet.
PMID- 28417720
TI - A longitudinal study of the effect of Antarctic residence on energy dynamics and
aerobic fitness.
AB - OBJECTIVES: To investigate the effect of Antarctic residence on energy dynamics
and aerobic fitness over the course of a year in over-wintering personnel. STUDY
DESIGN: A prospective longitudinal observational study. METHODS: A convenience
sample of personnel over-wintering at Rothera Research Station in Antarctica was
studied. Body weight, body fat, food intake, activity and aerobic fitness were
recorded every 30 days for 1 year. Body weight, body fat and food intake were
measured using weighing scales, skinfold callipers and diet records,
respectively; activity was measured using accelerometer-based activity trackers
and aerobic fitness using a treadmill protocol. Climate markers of temperature
and sunlight hours were also recorded. RESULTS: Twenty-one subjects took part in
the study over the 12-month period. A statistically significant increase in body
weight and body fat in winter was observed (p=0.012 and p=0.049, respectively).
There were no statistically significant trends in activity, food intake or
aerobic fitness. CONCLUSIONS: There were significant seasonal changes in body
weight and body fat, with both measures increasing in winter but no significant
changes in the other main outcome measures.
PMID- 28417721
TI - Physical activity and fitness in 8-year-old overweight and normal weight children
and their parents.
AB - OBJECTIVES: To compare the physical fitness and physical activity of 8-year-old
overweight children (n = 53) to normal weight children (n = 65), and to determine
whether a significant relationship exists between physical activity of parents
and their children. STUDY DESIGN: A cross-sectional study. METHODS: A total of
119 children from Northern Finland were recruited for the study. Waist
circumference, height, weight and BMI were measured. Physical activity of the
children and their parents was determined with self-administered 7-day recall
questionnaires (PAQ-C). Physical fitness of the children was evaluated with 7
items of the EUROFIT-test battery (flamingo balance test, plate tapping, sit-and
reach test, sit-ups, bent arm hang and 10*5 shuttle run). Aerobic capacity of the
children was tested with 6-minute walking test. RESULTS: Overweigh was related to
impaired performance in tests requiring muscle endurance, balance, explosive
power of lower extremities, upper body strength and endurance, speed and agility
in both genders and aerobic capacity in boys. Physical activity levels of
overweight boys (2.41 SD 0.72) were lower than their lean counterparts (2.91 SD
0.64, p = 0.004); no such difference was observed in girls (2.53 SD 0.64 vs. 2.59
SD 0.68, p = 0.741). Physical activity was significantly associated with better
performance in several physical fitness tests in boys, but not in girls. Mothers'
physical activity was associated with children's physical activity (r = 0.363, p
< 0.001), but no such association was found between fathers and children (r =
0.019, p = 0.864). CONCLUSION: This study shows an inverse relationship between
excess bodyweight and physical fitness in children. Mother-child relationship of
physical activity appeared to be stronger than father-child relationship.
Improving physical fitness in children through physical activity might require
interventions that are responsive to the ability and needs of overweight children
and their families and focus on helping parents and children to be physically
active together.
PMID- 28417723
TI - Re: Vitamin D deficiency among northern Native Peoples.
PMID- 28417722
TI - Health consumption in Sami speaking municipalities and a control group with
regard to medical imaging.
AB - OBJECTIVES: The Northern Norway Regional Health Authority trust aims to offer a
high quality specialist health care to all inhabitants. The objective of this
study was to document the consumption of medical imaging [conventional
radiography (CR), computerised tomography (CT), magnetic resonance (MR),
ultrasound (US)]. METHODS: The eight municipalities in northern Norway included
in the administration area of the Sami language law (Sami group - 132,490
persons/year in the period 2003-2009, mean/year 19,363 inhabitants) were matched
with a control group of 11 municipalities (non-Sami group - 135,539 persons/year,
mean/year 18,927 inhabitants). Population data was accessed from Statistics
Norway. Data on imaging exams were derived from a regional database including
production data from all public and private institutions within the region. All
four main modality groups (CR, CT, MR, US) were analysed. Variations for imaging
frequency on each modality were compared between the Sami and non-Sami
municipalities. RESULTS: A total of 278,832 exams were performed during study
period. The age adjusted exam rate (all modalities) was significantly higher (p <
0.001) in non-Sami (females and males) group. There was no difference with regard
to conventional radiography (CR) (p = 0.855). Whereas MR (p < 0.001) imaging was
more common in the Sami group, CT (p < 0.001) and US (p = 0.003) exams were more
frequently used in the control group. CONCLUSION: People living in Sami speaking
communities experienced significantly less CT and US exams, but had more MR exams
than the control group. A relatively high physical activity, obesity and a lower
risk of cancer may be explanations.
PMID- 28417724
TI - Factors related to fruit, vegetable and traditional food consumption which may
affect health among Alaska Native People in Western Alaska.
AB - OBJECTIVES: Determine intake of fruits, vegetables and traditional foods (TF),
availability of foods, and attitudes towards increasing their consumption. STUDY
DESIGN: Establish community baseline through a cross-sectional sample of
residents who were weighed, measured and interviewed. Village stores were
surveyed for food availability, price and quality. METHODS: Eighty-eight
respondents self-identified as the household member primarily responsible for
food shopping and cooking were surveyed in 3 Western Alaska Native villages using
a food frequency questionnaire, and village stores were evaluated using food
environment surveys. RESULTS: Overweight (BMI[kg/m2] > 25) was present in 68% of
participants. Fruit and vegetable intake (3.3 median servings/day) was low in
comparison to recommended intakes of 5-9 servings/d. Seventy-two per cent were
eating less than 5 servings/d of fruits and vegetables combined. Thirty-four per
cent of respondents were trying to eat more vegetables; 41% were trying to eat
more fruits. The median number of servings of TF was 3.2/d (mean 4.3/d). Seventy
seven per cent of respondents reported that they ate enough TF. CONCLUSION:
Recommendations to continue use of TF and increase intake of fruits and
vegetables are consistent with local attitudes. Our findings indicate that
increasing the availability of fruits and vegetables would be well received.
Information from this study provides a basis for nutrition education and food
supplement programs that is responsive to the needs and perceptions of the
residents. Continued TF intake and increased fruit and vegetable intake have the
potential to benefit the health of rural residents.
PMID- 28417725
TI - Traditional food consumption behaviour and concern with environmental
contaminants among Cree schoolchildren of the Mushkegowuk territory.
AB - OBJECTIVES: To investigate factors influencing consumption of traditional foods
(e.g. wild game, fish) and concerns about environmental contaminants among
schoolchildren of the Mushkegowuk Territory First Nations (Moose Factory, Fort
Albany, Kashechewan, Attawapiskat, and Peawanuck). STUDY DESIGN: Cross-sectional
data collection from a Web-based Eating Behaviour Questionnaire (WEB-Q). METHODS:
Schoolchildren in grades 6-12 (n = 262) responded to 4 of the WEB-Q questions:
(a) Do you eat game? (b) How often do you eat game? (c) How concerned are you
about the environmental contaminants in the wild game and fish that you eat? (d)
I would eat more game if... [6 response options]. Data were collected in 2004
(Fort Albany), 2005 (Peawanuck), 2006 (Attawapiskat), 2007 (Moose Factory) and
2009 (Kashechewan). Hierarchical log-linear modelling (LLM) was used for analyses
of multi-way frequency data. RESULTS: Of the schoolchildren answering the
specific questions: 174 consumed game; 95 reported concerns about contaminants in
game; and 84 would increase their game consumption if it were more available in
their homes. LLM revealed significant differences between communities;
schoolchildren in Moose Factory consumed game "rarely or never" at greater than
expected frequency, and fewer than expected consumed game "at least once a day".
Schoolchildren in Kashechewan had greater frequency of daily game consumption and
few were concerned about contaminants in game. Using LLM, we found that sex was
an insignificant variable and did not affect game consumption frequency or
environmental contaminant concern. CONCLUSION: The consumption of traditional
foods differed between communities and appears to be related to contamination
concerns. In addition, latitudinal variation appears to influence the frequency
of traditional food consumption in children; children in the most southerly
location consumed traditional food less frequently.
PMID- 28417726
TI - Heart rate is associated with markers of fatty acid desaturation: the GOCADAN
study.
AB - OBJECTIVES: To determine if heart rate (HR) is associated with desaturation
indexes as HR is associated with arrhythmia and sudden death. STUDY DESIGN: A
community based cross-sectional study of 1214 Alaskan Inuit. METHODS: Data of FA
concentrations from plasma and red blood cell membranes from those >=35 years of
age (n = 819) were compared to basal HR at the time of examination. Multiple
linear regression with backward stepwise selection was employed to analyze the
effect of the desaturase indexes on HR, after adjustment for relevant covariates.
RESULTS: The Delta5 desaturase index (Delta5-DI) measured in serum has recently
been associated with a protective role for cardiovascular disease. This index
measured here in plasma and red blood cells showed a negative correlation with
HR. The plasma stearoyl-CoA-desaturase (SCD) index, previously determined to be
related to cardiovascular disease (CVD) mortality, on the other hand, was
positively associated with HR, while the Delta6 desaturase index (Delta6-DI) had
no significant effect on HR. CONCLUSION: Endogenous FA desaturation is associated
with HR and thereby, in the case of SCD, possibly with arrhythmia and sudden
death, which would at least partially explain the previously observed association
between cardiovascular mortality and desaturase activity.
PMID- 28417727
TI - Metabolic profile in two physically active Inuit groups consuming either a
western or a traditional Inuit diet.
AB - OBJECTIVES: To evaluate the effect of regular physical activity on metabolic risk
factors and blood pressure in Inuit with high BMI consuming a western diet (high
amount of saturated fatty acids and carbohydrates with a high glycemic index).
STUDY DESIGN: Cross sectional study, comparing Inuit eating a western diet with
Inuit eating a traditional diet. METHODS: Two physically active Greenland Inuit
groups consuming different diet, 20 eating a traditional diet (Qaanaaq) and 15
eating a western diet (TAB), age (mean (range)); 38, (22-58) yrs, BMI; 28 (20-40)
were subjected to an oral glucose tolerance test (OGTT), blood sampling, maximal
oxygen uptake test, food interview/collection and monitoring of physical
activity. RESULTS: All Inuit had a normal OGTT. Fasting glucose (mmol/l), HbA1c
(%), total cholesterol (mmol/l) and HDL-C (mmol/l) were for Qaanaaq women: 4.8+/
0.2, 5.3+/-0.1, 4.96+/-0.42, 1.34+/-0.06, for Qaanaaq men: 4.9+/-0.1, 5.7+/-0.1,
5.08+/-0.31, 1.28+/-0.09, for TAB women: 5.1+/-0.2, 5.3+/-0.1, 6.22+/-0.39,
1.86+/-0.13, for TAB men: 5.1+/-0.2, 5.3+/-0.1, 6.23+/-0.15, 1.60+/-0.10. No
differences were found in systolic or diastolic blood pressure between the
groups. There was a more adverse distribution of small dense LDL-C particles and
higher total cholesterol and HDL-C concentration in the western diet group.
CONCLUSIONS: Diabetes or impaired glucose tolerance was not found in the Inuit
consuming either the western or the traditional diet, and this could, at least
partly, be due to the high amount of regular daily physical activity. However,
when considering the total cardio vascular risk profile the Inuit consuming a
western diet had a less healthy profile than the Inuit consuming a traditional
diet.
PMID- 28417728
TI - Frequent use of primary health care service in Greenland: an opportunity for
undiagnosed disease case-finding.
AB - OBJECTIVES: To estimate the age- and gender-specific consultation rates of
patients who availed primary health care service in Greenland and to analyse
contact patterns among patients in Nuuk. DESIGN: Observational and cross
sectional register study using data captured from the medical records. MATERIALS
AND METHODS: The number of patients specified by age and gender who had contacted
the primary health care centres within the last year was identified using a
statistic module applied to the electronic medical records system. The population
as it was on the 1st of January 2011 was used as the background population. The
age- and gender-specific consultation rates were calculated. Review of most
recent contact was performed in a subsample of patients from Nuuk, and
information of the type of contact and diagnoses was obtained. RESULTS: Eighty
three percent of the population in Greenland had been in contact with the primary
health care centre within the last year. Females were more frequent users than
males. A subsample of 400 patients in Nuuk was identified. Personal contact was
the most frequent type of consultation (75.8%), followed by telephone (14.8%) and
e-mail (9.8%) consultations. Musculoskeletal symptoms accounted for the most
frequent bases for diagnoses. CONCLUSION: More than 80% of the whole population
has been in contact with the primary health care system within the last year.
This indicates that opportunistic case-finding of chronic diseases such as
diabetes, hypertension, etc. providing a possible strategy for decreasing the
number of undiagnosed cases.
PMID- 28417729
TI - Preterm birth in the Inuit and First Nations populations of Quebec, Canada, 1981
2008.
AB - OBJECTIVES: To evaluate preterm birth (PTB) for Inuit and First Nations vs. non
Indigenous populations in the province of Quebec, Canada. STUDY DESIGN:
Retrospective cohort study. METHODS: We evaluated singleton live births for
Quebec residents, 1981-2008 (n = 2,310,466). Municipality of residence (Inuit
inhabited, First Nations-inhabited, rest of Quebec) and language (Inuit, First
Nations, French/English) were used to identify Inuit and First Nations births.
The outcome was PTB (<37 completed weeks). Cox proportional hazards regression
was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) of
PTB, adjusting for maternal age, education, marital status, parity and birth
year. RESULTS: PTB rates were higher for Inuit language speakers in Inuit
inhabited areas and the rest of Quebec compared with French/English speakers in
the rest of Quebec, and disparities persisted over time. Relative to
French/English speakers in the rest of Quebec, Inuit language speakers in the
rest of Quebec had the highest risk of PTB (HR 1.98, 95% CI: 1.62-2.41). The risk
was also elevated for Inuit language speakers in Inuit-inhabited areas, though to
a lesser extent (HR 1.29, 95% CI: 1.18-1.41). In contrast, First Nations language
speakers in First Nations-inhabited areas and the rest of Quebec had similar or
lower risks of PTB relative to French/English speakers in the rest of Quebec.
CONCLUSIONS: Inuit populations, especially those outside Inuit-inhabited areas,
have persistently elevated risks of PTB, indicating a need for strategies to
prevent PTB in this population.
PMID- 28417730
TI - From science to action and from action to science: the Nunavik Trichinellosis
Prevention Program.
AB - OBJECTIVES: During the 1980s, walrus-meat consumption caused infections with the
parasite Trichinella nativa in Nunavik inhabitants. In response to these events,
stakeholders set up the community-based Nunavik Trichinellosis Prevention Program
(NTPP). The objectives of the present communication are to review the NTPP,
describe how science and action were interwoven in its development and identify
its assets and limitations. STUDY DESIGN: Descriptive study. METHODS: The NTPP
relies on a pooled digestion assay of tongue samples taken from each harvested
walrus. The public health recommendations depend on the results of the analyses:
infected walrus meat should be destroyed; parasite-free meat may be eaten raw or
cooked. RESULTS: All communities involved in the walrus hunt participate in the
NTPP and a high percentage of harvested walruses are included in the NTPP.
Infected animals account for 2.9% of the walruses tested (20/694) since 1992. The
NTPP permitted the early management of a trichinellosis event in 1997. Since
then, it prevented the new occurrence of outbreaks related to walruses hunted by
Nunavimmiut. CONCLUSIONS: The absence of recent major outbreaks of trichinellosis
in Nunavik may reasonably be attributed to the NTPP. The success of the program
stands on many facilitating factors such as the nature of the disease and its
source, the existence of an efficient analytic method, the strong involvement of
the different partners including direct resource users, as well as the
comprehensive bidirectional science-to-action approach that has been followed.
PMID- 28417731
TI - Dietary quality and adequacy among Aboriginal alcohol consumers in the Northwest
Territories, Canada.
AB - OBJECTIVES: The present study aimed to assess dietary adequacy and quality among
Inuvialuit alcohol consumers and non-consumers in the Northwest Territories
(NWT), Canada. STUDY DESIGN: Cross-sectional study. METHODS: A validated
quantitative food frequency questionnaire was administered to individuals (n =
216) of randomly selected households in 3 NWT communities to capture dietary
intake and alcohol consumption over a 30-day recall period. The daily energy and
nutrient intake, dietary adequacy and the top food sources of energy and selected
nutrients were determined by alcohol consumption status. RESULTS: Energy intake
was higher among all alcohol consumers regardless of gender. Male alcohol
consumers had lower nutrient intake density (per 4,184 kJ) of protein,
cholesterol and several micronutrients (p <= 0.05), and female alcohol consumers
had lower intake density of saturated fat (p <= 0.01), thiamine, folate and
sodium (p <= 0.05). Among all men and women, 70-100% had inadequate intakes of
dietary fibre, vitamin E and potassium. Non-nutrient-dense foods contributed
similar amounts and traditional foods (TF) contributed 3% less to energy
comparing alcohol consumers to non-consumers. CONCLUSION: Nutrient inadequacies
are prevalent among Aboriginal populations in the Canadian Arctic and may be
exacerbated by alcohol consumption due to alcohol's effects on dietary intake,
nutrient transport and metabolism. Adult Inuvialuit who consumed alcohol had
increased caloric intake and consumed similar amounts of non-nutrient-dense foods
and less nutrient-dense TF. Fewer dietary inadequacies were observed among
alcohol consumers than non-consumers, which might be due to the increase in
overall food intake among alcohol consumers; however, further exploration of
volume and pattern of drinking might help explain this result.
PMID- 28417732
TI - Climate change and zoonotic infections in the Russian Arctic.
AB - Climate change in the Russian Arctic is more pronounced than in any other part of
the country. Between 1955 and 2000, the annual average air temperature in the
Russian North increased by 1.2 degrees C. During the same period, the mean
temperature of upper layer of permafrost increased by 3 degrees C. Climate change
in Russian Arctic increases the risks of the emergence of zoonotic infectious
diseases. This review presents data on morbidity rates among people, domestic
animals and wildlife in the Russian Arctic, focusing on the potential climate
related emergence of such diseases as tick-borne encephalitis, tularemia,
brucellosis, leptospirosis, rabies, and anthrax.
PMID- 28417733
TI - Dietary recommendations regarding pilot whale meat and blubber in the Faroe
Islands.
AB - For centuries the pilot whale has been an important part Faroese life - both in
regard to food and culture. However, studies dating back to 1977 have shown an
increase in contamination of the meat, blubber, liver and kidneys of pilot
whales. Several birth cohorts have been established in the Faroes in order to
discover the health effects related to mercury and organchlorine exposure. In
short the results have so far shown that: mercury from pilot whale meat adversely
affects the foetal development of the nervous system; the mercury effect is still
detectable during adolescence; the mercury from the maternal diet affects the
blood pressure of the children; the contaminants of the blubber adversely affect
the immune system so that the children react more poorly to immunizations;
contaminants in pilot whales appear to increase the risk of developing
Parkinson's disease in those who often eat pilot whale; the risk of hypertension
and arteriosclerosis of the carotid arteries is increased in adults who have an
increased exposure to mercury; septuagenarians with type 2 diabetes or impaired
fasting glycaemia tended to have higher PCB concentrations and higher past intake
of traditional foods, especially during childhood and adolescence. Also impaired
insulin secretion appears to constitute an important part of the type 2 diabetes
pathogenesis associated with exposure to persistent lipophilic food contaminants.
From the latest research results, the authors consider that the conclusion from a
human health perspective must be to recommend that pilot whale is no longer used
for human consumption.
PMID- 28417734
TI - Dietary exposure to persistent organic pollutants and metals among Inuit and
Chukchi in Russian Arctic Chukotka.
AB - OBJECTIVES: The general aim was to assess dietary exposure to selected persistent
organic pollutants (POPs) and metals among Eskimo (Inuit) and Chukchi of the
Chukotka Peninsula of the Russian Arctic, and to establish recommendations for
exposure risk reduction. STUDY DESIGN: A cross-sectional evaluation of
nutritional patterns of coastal and inland indigenous peoples of the Chukotka
Autonomous Okrug (in 2001-2003); assessment of the levels of persistent toxic
substances (PTSs) in traditional foods and their comparison to Russian food
safety limits; the identification of local sources of food contamination; and the
recommendation and implementation of risk management measures. METHODS: Community
based dietary survey of self reported food frequencies (453 persons), chemical
analyses (POPs and metals) of local foods and indoor matters (397 samples),
substantiation of recommendations for daily (weekly, monthly) intakes of
traditional food. RESULTS: POPs in traditional food items are generally below the
Russian food safety limits except marine mammal fat, while Hg and Cd are high
mainly in mammal viscera. Lead is relatively low in tissues of all animals
studied. For the Chukotka coastal communities, seals constitute the principal
source of the whole suite of PTSs considered. Consumption restrictions are
recommended for marine and freshwater fish, some wild meats (waterfowl and seal),
fats (whale and seal), liver (most animals) and kidney (reindeer, walrus and
seal). Evidence is presented that contamination of foodstuffs may be
significantly increased during storing/processing/cooking of food due to indoor
and outdoor environmental conditions. CONCLUSIONS: Based on the analytical
findings and the local PTSs sources identified, guidelines on food safety are
suggested, as well as measures to reduce food contamination and domestic and
local sources. Important and urgent remedial actions are recommended to minimize
PTSs environmental and domestic contamination. Waste clean-up activities started
in coastal Chukotka in 2007.
PMID- 28417735
TI - Lead exposure in Nunavik: from research to action.
AB - BACKGROUND: In 1999, the Government of Canada regulated the use of lead shot for
hunting. Concurrently, the Nunavik Regional Board of Health and Social Services
(NRBHSS) was informed of the results of an isotope study that pointed to lead
ammunition as a likely source of lead exposure in Nunavik. Rapidly thereafter, a
coalition for the banning of lead shot was implemented by the NRBHSS as well as
by regional/local partners and by Inuit hunters in order to disseminate this
information to the public. OBJECTIVES: The purpose of this article is to describe
the intervention conducted in the winter of 1999 by the NRBHSS and to assess the
combined impact of national legislation and an awareness campaign on blood lead
levels in Nunavik. STUDY DESIGN: Impact assessment of the intervention for the
banning of lead shot conducted in 1999 in Nunavik using blood lead levels data
before and after the intervention. METHODS: Data on blood lead levels in Nunavik
describing foetal exposure as well as during childhood and in adults published
between 1992 and 2009 were compiled. Blood lead levels in Nunavik prior to and
after the interventions were compared. To assess the current situation, the most
recent blood lead levels were compared with those from surveys conducted during
the same period in North America. RESULTS: Analysis of blood samples collected
from umbilical cord and from adults show that blood lead levels in Nunavik
significantly declined between 1992 and 2004. Nevertheless, lead exposure in
Nunavik still remains higher in comparison to that observed in other North
American surveys. CONCLUSIONS: The current situation regarding lead exposure in
Nunavik has significantly improved as a result of the implemented intervention.
However, according to recent data, a gap still subsists relative to other North
American populations.
PMID- 28417736
TI - The role of Indigenous knowledge in environmental health risk management in
Yukon, Canada.
AB - OBJECTIVES: This project aimed to gain better understandings of northern
Indigenous risk perception related to food safety and to identify the role that
Indigenous knowledge (IK) plays in risk management processes to support more
effective and culturally relevant benefit-risk (B-R) management strategies. STUDY
DESIGN: The project used an exploratory qualitative case study design to
investigate the role and place of IK in the management of environmental
contaminants exposure via consumption of traditional foods in Yukon First Nations
(YFNs). METHODS: Forty-one semi-directive interviews with Traditional Food
Knowledge Holders and Health and Environment Decision-makers were conducted. A
review and analysis of organizational documents related to past risk management
events for the issue was conducted. Thematic content analysis was used to analyze
transcripts and documents for key themes related to the research question.
RESULTS: There was a recognized need by all participants for better collaboration
between scientists and YFN communities. YFNs have been involved in identifying
and defining community concerns about past risk issues, setting a local context,
and participating in communications strategies. Interviewees stressed the need to
commit adequate time for building relationships, physically being in the
community, and facilitating open communication. Conducting community-based
projects was identified as critical for collaboration and for cooperative
learning and management of these issues. CONCLUSIONS: The perception of
"effective" benefit-risk management is significantly influenced by the efforts
made to include local communities in the process. A set of common guiding
principles within a process that brings together people and knowledge systems may
provide a more effective way forward in cross-cultural, multiple knowledge system
contexts for complex benefit-risk issues than a prescriptive rigid framework.
PMID- 28417737
TI - A Wellness Course for Community Health Workers in Alaska: "wellness lives in the
heart of the community".
AB - OBJECTIVES: To develop, implement, and evaluate a culturally respectful Wellness
Course with and for Alaska's village-based Community Health Workers (CHWs) to
support community health promotion and disease prevention. STUDY DESIGN: This
article describes Wellness Course development, implementation, and evaluation.
METHODS: Five 5-day Wellness Courses were provided for 55 CHWs from communities
throughout Alaska. Fifty-two of 55 participants completed a post-course written
evaluation. Post-course telephone interviews were conducted with participants
(11/32) from the first 3 courses. RESULTS: On written post-course evaluations,
all participants wrote detailed descriptions of what they learned and 98% (51/52)
felt more confident in their knowledge and ability to present community wellness
information. As a result of course participation, 88% (46/52) of CHWs wrote ways
they would support family and community wellness, and 85% (44/52) wrote ways they
planned to take better care of their health. During the in-depth post-course
interviews, all 11 CHWs interviewed described ways the Wellness Course increased
their health knowledge, helped them in their work, and prepared them to
effectively engage with their communities to promote health. CONCLUSIONS:
Learning wellness information with hands-on activities and practising health
presentation and community engagement skills within the course design increased
participants' wellness knowledge and skills, confidence, and motivation to
provide community wellness activities. Techniques for active listening, engaging
community, and using the arts and storytelling as culturally respectful health
promotion are tools that when used by CHWs within their own community have
potential to empower community wellness.
PMID- 28417738
TI - Survival of Sami cancer patients.
AB - OBJECTIVES: The incidence of cancer among the indigenous Sami people of Northern
Finland is lower than among the Finnish general population. The survival of Sami
cancer patients is not known, and therefore it is the object of this study. STUDY
DESIGN: The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31
December 1978 in the two Sami municipalities of Inari and Utsjoki, which are
located in Northern Finland and are 300-500 km away from the nearest central
hospital. The survival experience of Sami and non-Sami cancer patients diagnosed
in this cohort during 1979-2009 was compared with that of the Finnish patients
outside the cohort. METHODS: The Sami and non-Sami cancer patients were matched
to other Finnish cancer patients for gender, age and year of diagnosis and for
the site of cancer. An additional matching was done for the stage at diagnosis.
Cancer-specific survival analyses were made using the Kaplan-Meier method and Cox
regression modelling. RESULTS: There were 204 Sami and 391 non-Sami cancer cases
in the cohort, 20,181 matched controls without matching with stage, and 7,874
stage-matched controls. In the cancer-specific analysis without stage variable,
the hazard ratio for Sami was 1.05 (95% confidence interval 0.85-1.30) and for
non-Sami 1.02 (0.86-1.20), indicating no difference between the survival of those
groups and other patients in Finland. Likewise, when the same was done by also
matching the stage, there was no difference in cancer survival. CONCLUSION: Long
distances to medical care or Sami ethnicity have no influence on the cancer
patient survival in Northern Finland.
PMID- 28417739
TI - Snow crab allergy and asthma among Greenlandic workers - a pilot study.
AB - OBJECTIVES: To study snow crab sensitization, occupational allergy and asthma in
the snow crab industry in Greenland, as high rates have been found in Canada, but
no reports have emerged from the same industry in Greenland. STUDY DESIGN: Pilot
survey. METHODS: Twenty workers (19 of Inuit and 1 of other origin) in a snow
crab (Chionoecetes opilio) and Atlantic shrimp (Pandalus borealis) processing
plant in Greenland were assessed with skin prick tests (SPTs) with common
aeroallergens and specific allergens from snow crab and shrimp extracts,
spirometry, blood sampling for total IgE and specific IgE determination. Eighteen
workers contributed a questionnaire-based medical interview. RESULTS: Positive
skin prick test reactions were common to snow crab (40%) and shrimp (20%).
Specific IgE to snow crab were positive in 4 workers (21%). Two workers had
elevated total IgE levels. Symptoms suggestive of asthma were common (45%). Work
related symptoms of skin rash, rhinitis, and/or conjunctivitis were reported by
50%, and symptoms from the lower airways by 39%. Combining history of work
related symptoms with results from specific SPTs and/or specific IgE
determination suggested that 11 and 22% of workers suffered from probable and
possible occupational asthma, respectively, whereas 22% had possible occupational
dermatitis or rhinitis. CONCLUSIONS: Greenlander Inuit do not appear to be
protected against sensitization to snow crab or shrimp when occupationally
exposed to these. This pilot study suggests that occupational allergy and asthma
may be as common a problem in Greenlandic workers as in Canadian.
PMID- 28417740
TI - Living conditions, quality of life, adherence and treatment outcome in
Greenlandic HIV patients.
AB - OBJECTIVES: Despite a high level of sexually transmitted infections, HIV
incidence has remained quite stable in Greenland with 5-6 new cases per year
(approximately 10 per 100,000). However, disease control is suboptimal and
mortality is relatively high. The aim of the present study was to determine
associations between adherence to treatment and treatment outcome, living
conditions and quality of life among HIV patients in Greenland. MATERIAL AND
METHODS: Cross-sectional questionnaire-based cohort study of HIV patients in
Greenland during 2008-2009. Data regarding treatment, viral load, CD4 count, etc.
were obtained from a central HIV-database. RESULTS: Forty-six persons, 17 women
and 29 men, of the 60 registered HIV-positive patients (77%) were included.
Eighty percent were heterosexually infected and 17% by men having sex with men
(MSM) activity. Median age at the time of diagnosis was 48 years (range 20-63).
Eighty-nine percent received highly active antiretroviral therapy (HAART). Sixty
seven percent were adherent as defined by a combination of adherence to
appointments and to treatment. Ninety-seven percent of adherent and 17% non
adherent patients on HAART had HIV-RNA less than 200 copies per ml (RR=24.2,
p<0.0001). Poor adherence was associated with younger age (<50 years) (adjusted
RR=7.95, p=0.005) and living in remote areas with no direct contact with skilled
personnel (adjusted RR=6.75, p=0.01). Unsafe sex was also more frequent among non
adherent patients (RR=4.12, p=0.026), but due to few answers this topic was not
included in the multivariate model. CONCLUSION: The HIV population in Greenland
is peculiar since most patients are heterosexually infected and middle-aged at
diagnosis. A relatively poor adherence and consequently inferior treatment
outcome is related to young age and living in remote areas.
PMID- 28417741
TI - Bachelor studies for nurses organised in rural contexts - a tool for improving
the health care services in circumpolar region?
AB - OBJECTIVES: This article is based on a pilot study of Finnmark University
College's off-campus bachelor programme (BA) for nurses, organised in rural
areas. The objectives were to explore whether these courses had contributed to
reduced vacancies; whether the learning outcome of the off-campus courses was the
same as the on-campus programme, and how the education had influenced the nurses'
professional practice in local health services. STUDY DESIGN: In the study we
used mixed strategies in data collection and analyses. METHODS: Data about course
completion, average age, average grades and retention effect were collected in
2009/2010 from 3 off-campus classes and their contemporary on-campus classes.
Then 7 of the off-campus nurses were interviewed. A content analytical approach
to the data was employed. RESULTS: With retention of 93%, the off-campus BA
course for nurses has been one of the most effective measures, particularly in
rural areas. The employers' support for further education after graduating seems
to be an important factor for the high retention rate. Teaching methods such as
learning activities in small local groups influenced the nurses' professional
development. Local training grants, supervision and a local learning environment
were important for where they chose their first job after graduation.
CONCLUSIONS: The study confirms that nurses educated through off-campus courses
remain in the county over time after graduating. The "home-grown" nurses are
familiar with the local culture and specific needs of the population in this
remote area. The study confirms findings in other studies, that further education
is an important factor for nurses' retention.
PMID- 28417742
TI - Socioeconomic characteristics and health outcomes in Sami speaking municipalities
and a control group in northern Norway.
AB - OBJECTIVES: The Sami people constitute an ethnic minority in northern Norway. The
objectives of this study were to compare municipalities with a majority of Sami
in the population and a control group with regard to socioeconomic factors and
health outcome. METHODS: Original data from Statistics Norway and Directorate of
health on socioeconomic factors (education, unemployment, disability, poverty)
and health outcomes [total mortality, cancer specific mortality, cardiovascular
disease (CVD) specific mortality] were imported from the "Health Atlas" at the
Northern Norway Regional Health Authority (NNRHA) trust. The 8 municipalities in
the administration area of the Sami language law (Sami-majority group - 18,868
inhabitants) was compared with a control group consisting of 11 municipalities
where the Sami constitute a small minority in the population (18,931
inhabitants). Most data were from 2005 and 2008. RESULTS: There was no
significant difference in socioeconomic factors. Overall, cancer- and CVD
specific mortality rates were similar in both groups. The life expectancy was
significantly longer among women in the Sami-majority area (81.3 vs. 79.5 years,
p=0.035) and males (74.5 vs. 72.0 years, p=0.037). CONCLUSION: Socioeconomic
factors and cause-specific mortality rate were similar in the Sami-majority group
and the control group. Residents of both sexes in Sami-majority areas enjoyed
longer life expectancy.
PMID- 28417743
TI - Coming of age: how young women in the Northwest Territories understand the
barriers and facilitators to positive, empowered, and safer sexual health.
AB - OBJECTIVES: Compared to other young Canadians, youth in the Northwest Territories
(NWT) suffer disproportionately from negative sexual health outcomes, including
high rates of sexually transmitted infections and unintended pregnancies. This
study aimed to identify the self-perceived barriers and facilitators to positive,
empowered, and safer sexual health that impact female youth in the NWT. STUDY
DESIGN AND METHODS: A total of 12 females aged 15-19 who live in the NWT were
recruited through purposive sampling to participate in semi-structured, face-to
face interviews. Inductive coding and thematic analysis of transcribed data
occurred using Atlas.ti. RESULTS: Overall 4 main themes influenced the sexual
health of these women: sexual health knowledge, relationships with the self and
others, access to quality sexual health resources, and alcohol use/abuse.
CONCLUSION: Recommendations for future action include improving the content and
delivery of sexual health education, enhancing parent-adolescent sexual health
communication, providing workshops to empower young women to assert themselves
within relationships, and supporting an environment that normalizes youth
sexuality.
PMID- 28417744
TI - Higher body mass, older age and higher monounsaturated fatty acids intake reflect
better quantitative ultrasound parameters in Inuit preschoolers.
AB - OBJECTIVES: Investigate the effects of selected factors associated with
quantitative ultrasound parameters among Inuit preschoolers living in Arctic
communities (56 degrees 32'-72 degrees 40'N). MATERIALS AND METHODS: Children
were selected randomly in summer and early fall (n=296). Dietary intake was
assessed through the administration of a 24-h dietary recall (24-h recall) and a
food frequency questionnaire (FFQ). Anthropometry was measured using standardized
procedures. Plasma 25-hydroxy vitamin D (25(OH)D) and parathyroid hormone (PTH)
were measured using a chemiluminescent assay (Liaison, Diasorin). Quantitative
ultrasound parameters were measured using Sahara Sonometer, (Hologic Inc.).
RESULTS: Children divided by speed of sound (SoS) and broadband ultrasound
attenuation (BUA) quartiles were not different for age (years), sex (M/F),
calcium (mg/d) and vitamin D intake (ug/d) and plasma 25(OH)D concentration
(nmol/L). However, children in the highest BUA and SoS quartile had higher body
mass index (BMI) compared to those in quartile 1. Using multivariate linear
regression, higher BMI, older age and monounsaturated fatty acids (MUFA) intake
were predictors of BUA while only BMI was a predictor of SoS. CONCLUSIONS:
Further investigation assessing intakes of traditional foods (TF) and nutrients
affecting bone parameters along with assessment of vitamin D status of Inuit
children across seasons is required.
PMID- 28417745
TI - Level of selected nutrients in meat, liver, tallow and bone marrow from semi
domesticated reindeer (Rangifer t. tarandus L.).
AB - OBJECTIVES: To acquire new knowledge on the nutritional composition of semi
domesticated reindeer (Rangifer t. tarandus L.) and their nutritional value for
humans. The results could be useful in updating the Norwegian Food Composition
Database, whose current data on reindeer is limited. STUDY DESIGN: Cross
sectional study on population of semi-domesticated reindeer from 2 northern
Norwegian counties (Finnmark and Nordland). METHODS: Semi-domesticated reindeer
carcasses (n=31) were randomly selected, from which meat, liver, tallow and bone
marrow samples were collected. Selected vitamins, minerals, fatty acids and total
lipids were studied. RESULTS: As expected, reindeer meat was found to be lean (2%
total lipid), thus it is a good source of low-fat meat. The meat was also found
to be a good source of vitamin B12, docosapentaenoic acid (C22:5 n-3) and alpha
linolenic acid (C18:3 n-3). Statistically significant differences (p<0.05) in
most of the nutrient levels between meat and the rest of the studied reindeer
tissues were observed. In most cases, the liver, tallow and bone marrow had
higher nutritional values when compared to meat. Liver had the highest
concentrations of vitamin A, all vitamin B types, vitamin C, iron, selenium and
the total amount of polyunsaturated fatty acids (n-3). Additionally, liver was
the only edible tissue that contained vita-mins B9 and C. The vast majority of
the vitamin concentrations in liver, tallow and bone marrow were significantly
correlated with the concentrations in meat (p<0.05). CONCLUSIONS: The studied
tissues from reindeer demonstrated that reindeer is a valuable food source that
could meet or contribute to the consumers' nutritional recommended daily
allowance (RDA). 1Published 'ahead-of-print' 8 November 2011 (at www.ijch.fi ) in
accordance with previous publisher's routines.
PMID- 28417746
TI - Mammographic screening in Sami speaking municipalities and a control group. Are
early outcome measures influenced by ethnicity?
AB - Objectives . Female citizens of Sami (the indigenous people of Norway)
municipalities in northern Norway have a low risk of breast cancer. The objective
of this study was to describe the attendance rate and outcome of the Norwegian
Breast Cancer Screening Program (NBCSP) in the Sami-speaking municipalities and a
control group. Study design . A retrospective registry-based study. Methods . The
8 municipalities included in the administration area of the Sami language law
(Sami) were matched with a control group of 11 municipalities (non-Sami).
Population data were accessed from Statistics Norway. Data regarding invitations
and outcome in the NBCSP during the period 2001-2010 was derived from the Cancer
Registry of Norway (CRN). The NBCSP targets women aged 50-69 years. Rates and
percentages were compared using chi-square test with a p-value<0.05 as
statistical significant. Results . The attendance rate in the NBCSP was 78% in
the Sami and 75% in the non-Sami population (p< 0.01). The recall rates were 2.4
and 3.3% in the Sami and non-Sami population, respectively (p<0.01). The rate of
invasive screen detected cancer was not significantly lower in the Sami group
(p=0.14). The percentage of all breast cancers detected in the NBCSP among the
Sami (67%) was lower compared with the non-Sami population (86%, p=0.06).
Conclusion . Despite a lower risk of breast cancer, the Sami attended the NBCSP
more frequently than the control group. The recall and cancer detection rate was
lower among the Sami compared with the non-Sami group.
PMID- 28417748
TI - Demographic and contextual factors associated with inhalant use among youth in
rural Alaska.
AB - BACKGROUND: Abuse of harmful legal products that can be inhaled or ingested is a
serious and growing problem in many rural Alaskan communities, and particularly
so among preteens. METHODS: This study analyses data collected during baseline
measurements of a 5-year NIH/NIDA-funded study entitled A Community Trial to
Prevent Youth's Abuse of Harmful Legal Products in Alaska. Youth in 8 communities
located throughout the state participated in a survey during the fall of 2009 to
measure the prevalence and availability of harmful legal products (n=697). The
goal of the analysis presented here is to compare the contextual factors of
inhalant users and non-users in rural Alaskan communities. RESULTS: As reported
in national surveys of substance use among youth, participants in this study
indicated using alcohol more than any other substance. Inhalants were the second
most common substance abused, higher than either cigarettes or marijuana.
Lifetime use varied among demographic factors such as age, gender and ethnicity
as well as contextual factors including academic performance, parent employment,
household living situation and income. When compared to non-users, significantly
larger proportions of participants reporting lifetime inhalant use indicated easy
availability of inhalants in their home, school and retail outlets. Users were
also significantly more likely than non-users to have consumed alcohol.
CONCLUSION: Results of this study may inform the development of effective
interventions in other rural communities.
PMID- 28417749
TI - Traditional food consumption is associated with higher nutrient intakes in Inuit
children attending childcare centres in Nunavik.
AB - OBJECTIVES: To describe traditional food (TF) consumption and to evaluate its
impact on nutrient intakes of preschool Inuit children from Nunavik. DESIGN: A
cross-sectional study. METHODS: Dietary intakes of children were assessed with a
single 24-hour recall (n=217). TF consumption at home and at the childcare
centres was compared. Differences in children's nutrient intakes when consuming
or not consuming at least 1 TF item were examined using ANCOVA. RESULTS: A total
of 245 children attending childcare centres in 10 communities of Nunavik were
recruited between 2006 and 2010. The children's mean age was 25.0+/-9.6 months
(11-54 months). Thirty-six percent of children had consumed at least 1 TF item on
the day of the recall. TF contributed to 2.6% of total energy intake. Caribou and
Arctic char were the most reported TF species. Land animals and fish/shellfish
were the main contributors to energy intake from TF (38 and 33%, respectively).
In spite of a low TF intake, children who consumed TF had significantly (p<0.05)
higher intakes of protein, omega-3 fatty acids, iron, phosphorus, zinc, copper,
selenium, niacin, pantothenic acid, riboflavin, and vitamin B12, and lower
intakes of energy and carbohydrate compared with non-consumers. There was no
significant difference in any of the socio-economic variables between children
who consumed TF and those who did not. CONCLUSION: Although TF was not eaten
much, it contributed significantly to the nutrient intakes of children.
Consumption of TF should be encouraged as it provides many nutritional, economic,
and sociocultural benefits.
PMID- 28417750
TI - Modern contact investigation methods for enhancing tuberculosis control in
Aboriginal communities.
AB - The Aboriginal communities in Canada are challenged by a disproportionate burden
of TB infection and disease. Contact investigation (CI) guidelines exist but
these strategies do not take into account the unique social structure of
different populations. Because of the limitations of traditional CI, new
approaches are under investigation and include the use of social network
analysis, geographic information systems and genomics, in addition to the
widespread use of genotyping to better understand TB transmission. Guidelines for
the routine use of network methods and other novel methodologies for TB CI and
outbreak investigation do not exist despite the gathering evidence that these
approaches can positively impact TB control efforts, even in Aboriginal
communities. The feasibility and efficacy of these novel approaches to CI in
Aboriginal communities requires further investigation. The successful integration
of these novel methodologies will require community involvement, capacity
building and ongoing support at every level. The outcome will not only be the
systematic collection, analysis, and interpretation of CI data in high-burden
communities to assess transmission but the prioritization of contacts who are
candidates for treatment of LTBI which will break the cycle of transmission.
Ultimately, the measure of success will be a clear and sustained decline in TB
incidence in Aboriginal communities.
PMID- 28417751
TI - Incidence of pancreatic cancer in Greenland 2000-2010.
AB - BACKGROUND: Inuit people are known to be at an increased risk of cancers usually
uncommon to the western world such as cancers of the nasopharynx and salivary
glands. But what is the trend regarding pancreatic cancer? OBJECTIVE: To
determine the incidence of pancreatic cancer (PC) in Greenland compared with
Denmark in the period 2000-2010. STUDY DESIGN: Retrospective register-based
study. Cases were retrieved from The Danish Cancer Register and The Greenlandic
Patient Register and stratified in 5-year age intervals for each year. Age
standardized incidence ratios (SIR) for each year for Greenland compared with
Denmark were calculated using the number of cases and the number of inhabitants
in each 5-year age interval and in each country. The average SIR for the entire
period was calculated using a weighted average. RESULTS: The study revealed a SIR
of 2.38 (95% CI: 1.97-2.86; p<0.0001) indicating a significantly increased
incidence of PC in Greenland compared with Denmark. A linear regression analysis
showed no significant change in the SIR over time (p for trend 0.25) as well as
no significant change isolated in Greenland (p for trend 0.8). Furthermore, the
Inuit were significantly younger at the time of diagnosis (mean 62.7 vs. 70.0;
p<0.0001). CONCLUSIONS: The age-standardized incidence of PC is 138% higher in
Greenland than in Denmark. A part of this could be explained by a higher
prevalence of smoking and DM-2. However, the impact of genetic factors cannot be
disregarded and should be subjected to further investigation.
PMID- 28417752
TI - Treatment eligibility in Alaska Native and American Indian persons with hepatitis
C virus infection.
AB - OBJECTIVES: Treatment with pegylated interferon and ribavirin may prevent
progression of liver disease among patients with chronic hepatitis C virus
infection (HCV). Treatment initiation is based on published clinical eligibility
criteria, patients' willingness to undergo treatment and likelihood of success.
We examined treatment eligibility in a cohort of Alaska Native and American
Indian persons with chronic HCV infection. STUDY DESIGN: Retrospective cohort
study. METHODS: Medical records of all treatment naive HCV RNA positive patients
given an appointment by hepatology specialty clinic staff in 2003 and 2007 were
evaluated by a hepatology provider to investigate documented reasons for
treatment deferral. RESULTS: Treatment was initiated in 4 of 94 patients (4%) in
2003 and 14 of 146 patients (10%) in 2007. Major reasons for treatment deferral
in 2003 versus 2007 included inconsistent appointment attendance (36% of
deferrals vs. 18%), active substance abuse (17% vs. 22%), patient decision (17%
vs. 27%), liver biopsy without fibrosis or normal ALT (8% vs. 3%), uncontrolled
psychiatric condition (7% vs. 7%) and concurrent medical condition (6% vs. 9%).
There was significant improvement in proportion of appointments attended in 2007
versus 2003 (76% vs. 67%, p = 0.04) and the percentage of patients attending at
least 1 appointment (84% vs. 66%, p = 0.002). CONCLUSIONS: Multiple reasons for
treatment deferral were documented. Despite a significant improvement in
hepatology clinic attendance and an increase in the number of patients started on
treatment in 2007 compared to 2003, the overall percentage of those treated
remained low.
PMID- 28417753
TI - Mycoplasma genitalium presence, resistance and epidemiology in Greenland.
AB - Objectives . Greenland reports the highest rates of chlamydial infection and
gonorrhea in the Arctic. Our objective was to determine the presence, and
describe the basic epidemiology, of Mycoplasma genitalium for Greenland. Study
design . Cross-sectional study. Methods . 314 residents from Nuuk and Sisimiut,
between the ages of 15 and 65 years, participated in "Inuulluataarneq" (the
Greenland Sexual Health Project) between July 2008 and November 2009.
Participants provided self-collected samples for sexually transmitted infection
(STI) testing and completed a sexual health survey. Descriptive statistics and
logistic regression were used to summarize the basic characteristics of STI cases
overall and M. genitalium and Chlamydia trachomatis specifically. Clinically
relevant characteristics in each full model were gender (male or female), age (in
years), age at sexual debut (in years), number of sexual partners in the past 3
months (continuous) and history of forced sex and community. Results . The
overall prevalence of STIs was 19.0%, specifically: 9.8% for M. genitalium and
9.4% for C. trachomatis; 100% of M. genitalium-positive cases carried macrolide
resistance determinants. Being female [OR = 3.2; 95% confidence interval (CI):
1.1-9.8] and younger age (OR = 0.9; 95% CI: 0.9-1.0) were associated with M.
genitalium positivity. Age was also associated with C. trachomatis (OR = 0.9; 95%
CI: 0.8-0.9) and STI positivity overall (OR = 0.9; 95% CI: 0.9-0.9). Conclusions
. We observed a high prevalence of M. genitalium and macrolide resistance in this
study. A better understanding of M. genitalium sequelae is needed to inform
policy around testing, treatment, control and antibiotic use.
PMID- 28417754
TI - Alaska Native people's perceptions, understandings, and expectations for research
involving biological specimens.
AB - OBJECTIVES: Members of racially and ethnically diverse groups have been
persistently underrepresented in biomedical research in general, possibly due to
mistrust with the medical and research community. This article describes the
perceptions, understandings, and expectations of Alaska Native people about
research involving the collection and storage of biological specimens. STUDY
DESIGN: Stratified focus groups. METHODS: Twenty-nine focus groups with Alaska
Native people (n = 178) were held in 14 locations using a semi-structured
moderator guide. ATLAS.ti was used for thematic analysis through iterative
readings and coding. Alaska Native peoples' perceptions, understandings, and
expectations of researcher beneficence, informed consent processes, and provision
of research findings were elicited. RESULTS AND CONCLUSIONS: Alaska Native people
desired extensive disclosure of information beyond that typically provided in
consent and results dissemination processes. Information germane to the
motivation and intent of researchers and specifics of specimen storage and
destruction were specifically requested. A clear and extensive process of
informed consent and continued improvements in sharing results may enhance the
transparency of research intent, conduct, and use of obtained results among
Alaska Native people. Meeting expectations may improve relationships between
researchers and the Alaska Native population which could result in increased
research participation. Our findings offer a guide for researchers and
communities when planning and implementing research with biological specimens.
PMID- 28417755
TI - Oral health in a First Nations and a non-Aboriginal population in Manitoba.
AB - OBJECTIVES: To analyze the prevalence of poor oral health and selected
determinants in First Nations (FN) and Caucasian samples in Manitoba, Canada.
STUDY DESIGN: Cross-sectional survey, nested in a cohort study. METHODS: FN and
Caucasian participants completed a questionnaire on socio-demographic variables,
oral health symptoms, and oral health-related behaviours as part of a broader
cohort study comparing these ethnic groups for different chronic immune mediated
diseases. RESULTS: Caucasians reported higher levels of employment, education,
and urban dwelling than FNs (p<0.001). FNs reported smoking more, and having
poorer oral health-related behaviours than Caucasians (p<0.001). After adjustment
for age and sex, FN reported having more oral health symptoms than Caucasians
(odds ratio (OR): 2.71; 95% confidence interval (CI): 1.73, 4.52), but the
association was reduced and not statistically significant after adjustment for
other socio-demographic variables (OR=1.34; 95% CI: 0.58, 3.10). Oral health
symptoms were associated with current smoking among FN (adjusted OR=2.67, 95% CI:
1.05, 6.78). Oral hygiene behaviours were significantly related to smoking
status, rural living and education for both groups. CONCLUSIONS: Oral health
related behaviours and smoking were found to be significant factors explaining
poor oral health, which were lower for the FNs cohort than the Caucasian sample.
However oral health and related behaviours were less related to their ethnicity
than to socio-demographic factors, suggesting that policies to change behaviour
will not result in lasting reductions in oral health differences between these
groups in Manitoba.
PMID- 28417756
TI - Gender differences in comorbidity of conduct disorder among adolescents in
Northern Finland.
AB - OBJECTIVES: Conduct disorder (CD) refers to a pattern of severe antisocial and
aggressive behaviour manifested in childhood or adolescence, with heavy costs to
society. Though CD is a common psychiatric diagnosis among adolescents of both
genders, gender differences in comorbidity of CD have been little studied. In
this study we examined gender differences among adolescents with CD in causes for
hospitalization, comorbid psychiatric diagnoses and somatic conditions. STUDY
DESIGN: The original study sample consisted of 508 inpatient adolescents in
Northern Finland (age 12-17); 155 of them (65 girls, 92 boys) fulfilled the DSM
IV criteria for CD. METHODS: Diagnosis of CD and psychiatric comorbidities were
obtained from the K-SADS-PL and somatic conditions from the EuropAsi. RESULTS: As
compared to boys with CD, suicidality (including suicidal ideation and behaviour)
was significantly more commonly the cause of hospitalization among girls with CD
(43% vs. 24%, p=0.013). Among somatic conditions, there was a significant
predominance in self-reported allergies among girls (60% vs. 25%, p<0.001). Girls
had more often diagnosed comorbid post-traumatic stress disorder (13% vs. 3%,
p=0.025) and marginally significantly more major depressive disorder (36% vs.
23%, p=0.086). CONCLUSIONS: Girls with CD seem to have an increased tendency to
develop both comorbid psychiatric and somatic conditions as well as suicidality.
New clinical aspects in treatment of CD and comorbid disorders among girls are
discussed.
PMID- 28417757
TI - Assessment of consumption of marine food in Greenland by a food frequency
questionnaire and biomarkers.
AB - OBJECTIVES: We studied the association and agreement between questionnaire data
and biomarkers of marine food among Greenland Inuit. DESIGN: Cross sectional
study. METHODS: The study population comprised 2,224 Inuit, age 18+ (43% men);
data collected 2005-2008 in Greenland. Using a food frequency questionnaire
(FFQ), we calculated consumption of seal, whale, and fish (g/day) and as
meals/month, intake of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
total N3, and mercury. We measured erythrocyte membrane fatty acids (FA) and
whole blood mercury (Hg). Associations were assessed by Pearson correlation and
agreement between the 2 methods was assessed by Bland-Altman plots depicting mean
difference between the methods. Using multiple linear regressions, the
associations were studied between whole blood mercury, erythrocyte FA and
frequency or gram per day of seal, whale, and fish. RESULTS: Partial correlations
ranged from r=0.16, p<0.0001 (DHA) to r=0.56, p<0.0001 (mercury). The best fitted
lines were found for mercury and DHA. Mean difference was negative for mercury
but positive for all the FA biomarkers. In a multiple logistic regression
analysis, the best association was found between whole blood mercury and seal
consumption, both as frequency in meals and actual intake gram per day: beta=1.07
ug (95% CI: 1.06; 1.08) and beta=1.04 ug (95% CI: 1.03; 1.04), respectively.
CONCLUSION: Mercury showed the best correlation and agreement between calculated
and measured values. Calculated actual intake in gram per day and frequency of
meals showed similar associations with whole blood mercury and erythrocyte
membrane FAs.
PMID- 28417758
TI - The impact of Action Schools! BC on the health of Aboriginal children and youth
living in rural and remote communities in British Columbia.
AB - OBJECTIVES: The aim of the study was to determine the short-term impact of a 7
month whole-school physical activity and healthy eating intervention (Action
Schools! BC) over the 2007-2008 school year for children and youth in 3 remote
First Nations villages in northwestern British Columbia. STUDY DESIGN: A pre
experimental pre/post design was conducted with 148 children and youth (77 males,
71 females; age 12.5+/-2.2 yrs). METHODS: We evaluated changes in obesity (body
mass index [wt/ht2] and waist circumference z-scores: zBMI and zWC), aerobic
fitness (20-m shuttle run), physical activity (PA; physical activity
questionnaire and accelerometry), healthy eating (dietary recall) and
cardiovascular risk (CV risk). RESULTS: zBMI remained unchanged while zWC
increased from 0.46+/-1.07 to 0.57+/-1.04 (p<0.05). No change was detected in PA
or CV risk but aerobic fitness increased by 22% (25.4+/-15.8 to 30.9+/-20.0 laps;
p<0.01). There was an increase in the variety of vegetables consumed (1.10+/-1.18
to 1.45+/-1.24; p<0.05) but otherwise no dietary changes were detected.
CONCLUSIONS: While no changes were seen in PA or overall CV risk, zWC increased,
zBMI remained stable and aerobic fitness improved during a 7-month intervention.
1Published 'ahead-of-print' 2 December 2011 (at www.ijch.fi ) in accordance with
previous publisher's routines.
PMID- 28417759
TI - Level and temporal trend of perfluoroalkyl acids in Greenlandic Inuit.
AB - OBJECTIVES: Perfluoroalkyl acids (PFAAs) have been detected in human blood,
breast milk and umbilical cord blood across the globe. PFAAs do accumulate in the
marine food chain in Arctic regions. In Greenland, increasing PFAA concentrations
were observed during 1982-2006 in ringed seals and polar bears. However, until
now, no data have been reported for PFAAs in Greenlandic Inuit. This study
assesses the level and temporal trend of serum PFAAs in Greenlandic Inuit. STUDY
DESIGN: Cross-section and temporal time trend survey. METHODS: Serum PFAA levels
were determined in 284 Inuit from different Greenlandic districts using liquid
chromatography-tandem mass spectrometry with electrospray ionization. The
temporal time trend of serum PFAAs in Nuuk Inuit during 1998-2005 and the
correlation between serum PFAAs and legacy persistent organic pollutants (POPs)
were explored. RESULTS: Serum PFAA levels were higher in Nuuk Inuit than in non
Nuuk Inuit. Within the same district, higher PFAA levels were observed for males.
An age-dependent, increasing trend of serum PFAA levels in the period from 1998
2005 was observed for Nuuk Inuit. For the pooled gender data, no significant
association between PFAAs and legacy POPs was observed for Nuuk Inuit while for
non-Nuuk Inuit this correlation was significant. No correlation between PFAAs and
legacy POPs was found for male Inuit, whereas significant correlation was
observed both for pooled female Inuit and for non-Nuuk Inuit females.
CONCLUSIONS: We suggest that sources other than seafood intake might contribute
to the observed higher PFAA levels in Nuuk Inuit compared to the pooled non-Nuuk
Inuit. 1Published 'ahead-of-print' 13 December 2011 (at www.ijch.fi ) in
accordance with previous publisher's routines.
PMID- 28417760
TI - Sami-speaking municipalities and a control group's access to somatic specialist
health care (SHC): a retrospective study on general practitioners' referrals.
AB - OBJECTIVES: The Sami people constitute the indigenous people in northern Norway.
The objective of this study was to clarify whether they have a similar supply of
somatic specialist health care (SHC) as others. METHODS: The referrals from
general practitioners (GPs) in the primary health care (PHC) in the
administration area of the Sami language law (8 municipalities) were matched with
a control group of 11 municipalities. Population data was accessed from
Statistics Norway and the time period 2007-2010 was analysed. The main outcome
was the number of referrals per 1,000 inhabitants according to age group, gender
and place of living. RESULTS: 504,292 referrals in northern Norway were
indentified and the Sami and control group constituted 23,093 and 22,541
referrals, respectively. The major findings were a similar referral ratio (RR)
(1.14 and 1.17) (p = 0.624) and women more commonly referred (female/male ratio
1.45 and 1.41) in both groups. GPs in both groups were loyal to their local
hospital trust. CONCLUSION: Inhabitants in Sami-speaking municipalities in
northern Norway have a similar supply of SHC services as controls. Inter
municipal variation was significant in both groups.
PMID- 28417761
TI - Obesity studies in the circumpolar Inuit: a scoping review.
AB - BACKGROUND: Among circumpolar populations, recent research has documented a
significant increase in risk factors which are commonly associated with chronic
disease, notably obesity. OBJECTIVE: The present study undertakes a scoping
review of research on obesity in the circumpolar Inuit to determine the extent
obesity research has been undertaken, how well all subpopulations and geographic
areas are represented, the methodologies used and whether they are sufficient in
describing risk factors, and the prevalence and health outcomes associated with
obesity. DESIGN: Online databases were used to identify papers published 1992
2011, from which we selected 38 publications from Canada, the United States, and
Greenland that used obesity as a primary or secondary outcome variable in 30 or
more non-pregnant Inuit ("Eskimo") participants aged 2 years or older. RESULTS:
The majority of publications (92%) reported cross-sectional studies while 8%
examined retrospective cohorts. All but one of the studies collected measured
data. Overall 84% of the publications examined obesity in adults. Those examining
obesity in children focused on early childhood or adolescence. While most (66%)
reported 1 or more anthropometric indices, none incorporated direct measures of
adiposity. Evaluated using a customized quality assessment instrument, 26% of
studies achieved an "A" quality ranking, while 18 and 39% achieved quality
rankings of "B" and "C", respectively. CONCLUSIONS: While the quality of studies
is generally high, research on obesity among Inuit would benefit from careful
selection of methods and reference standards, direct measures of adiposity in
adults and children, studies of preadolescent children, and prospective cohort
studies linking early childhood exposures with obesity outcomes throughout
childhood and adolescence.
PMID- 28417762
TI - Room for improvement in diabetes care among First Nations in northern Quebec
(Eeyou Istchee): reasonable management of glucose but poor management of
complications.
AB - OBJECTIVES: To evaluate the clinical management of type 2 diabetes in the Eeyou
Istchee communities of northern Quebec. STUDY DESIGN: Retrospective quality
assurance audit. METHODS: Patients with diabetes were identified using the Cree
Diabetes Information System. Charts of eligible patients were audited for
healthcare visits, glycemic control, blood pressure, lipid profile,
pharmacological treatment and complications for the 2006 calendar year. Analyses
were performed to assess the association of disease duration, age, target
glycemic and blood pressure control with diabetes complications. RESULTS: Half of
the patients (49.7%) achieved target HbA1c, 53.6% had a blood pressure of
<=130/80 and 58.7% had an LDL of <=2.5 mmol/L. The proportion of patients meeting
all 3 targets was low at 17.1%. The mean number of diabetes-related clinic visits
was high, with an average of 3.9 visits to a physician and an average of 8.7
visits to a registered nurse. Of patients with a documented diabetic
complication, 39.4% of patients were not being managed with an ACE/ARB and 48.2%
of patients were not prescribed a statin. CONCLUSIONS: These findings suggest a
possible treatment gap for risk factors and complications management. To
circumvent further increases in diabetes-related complications, emphasis should
be placed on improved healthcare worker training, greater use of clinical
management and patient education tools and improved communication during the
diabetes-related clinical visits. Development of a culturally appropriate
multidisciplinary approach towards improved understanding of diabetes and
multifactorial risk management for diabetic patients is essential for the
prevention of diabetic complications.
PMID- 28417763
TI - Design and methods in a survey of living conditions in the Arctic - the SLiCA
study.
AB - OBJECTIVES: The main objective of this study is to describe the methods and
design of the survey of living conditions in the Arctic (SLiCA), relevant
participation rates and the distribution of participants, as applicable to the
survey data in Alaska, Greenland and Norway. This article briefly addresses
possible selection bias in the data and also the ways to tackle it in future
studies. STUDY DESIGN: Population-based cross-sectional survey. METHODS:
Indigenous individuals aged 16 years and older, living in Greenland, Alaska and
in traditional settlement areas in Norway, were invited to participate. Random
sampling methods were applied in Alaska and Greenland, while non-probability
sampling methods were applied in Norway. Data were collected in 3 periods: in
Alaska, from January 2002 to February 2003; in Greenland, from December 2003 to
August 2006; and in Norway, in 2003 and from June 2006 to June 2008. The
principal method in SLiCA was standardised face-to-face interviews using a
questionnaire. RESULTS: A total of 663, 1,197 and 445 individuals were
interviewed in Alaska, Greenland and Norway, respectively. Very high overall
participation rates of 83% were obtained in Greenland and Alaska, while a more
conventional rate of 57% was achieved in Norway. A predominance of female
respondents was obtained in Alaska. Overall, the Sami cohort is older than the
cohorts from Greenland and Alaska. CONCLUSIONS: Preliminary assessments suggest
that selection bias in the Sami sample is plausible but not a major threat. Few
or no threats to validity are detected in the data from Alaska and Greenland.
Despite different sampling and recruitment methods, and sociocultural
differences, a unique database has been generated, which shall be used to explore
relationships between health and other living conditions variables.
PMID- 28417764
TI - Self-rated health and ethnicity: focus on indigenous populations.
AB - OBJECTIVES: Self-rated health (SRH) is a commonly used measure in surveys to
assess general health status or health-related quality of life. Differences have
been detected in how different ethnic groups and nationalities interpret the SRH
measure and assess their health. This review summarizes the research conducted on
SRH within and between ethnic groups, with a focus on indigenous groups. STUDY
DESIGN AND METHODS: A search of published academic literature on SRH and
ethnicity, including a comprehensive review of all relevant indigenous research,
was conducted using PubMed and summarized. RESULTS: A wide variety of research on
SRH within ethnic groups has been undertaken. SRH typically serves as an outcome
measure. Minority respondents generally rated their health worse than the
dominant population. Numerous culturally-specific determinants of SRH have been
identified. Cross-national and cross-ethnicity comparisons of the associations of
SRH have been conducted to assess the validity of SRH. While SRH is a valid
measure within a variety of ethnicities, differences in how SRH is assessed by
ethnicities have been detected. Research in indigenous groups remains generally
under-represented in the SRH literature. CONCLUSIONS: These results suggest that
different ethnic groups and nationalities vary in SRH evaluations, interpretation
of the SRH measure, and referents employed in rating health. To effectively
assess and redress health disparities and establish culturally-relevant and
effective health interventions, a greater understanding of SRH is required,
particularly among indigenous groups, in which little research has been
conducted.
PMID- 28417765
TI - High prevalence of lactase non-persistence among indigenous nomadic Nenets, north
west Russia.
AB - Objectives The frequency of adult-type hypolactasia (lactase non-persistence)
varies widely among different ethnic groups. The cultural historical hypothesis
assumes a link between the occurrence of hypolactasia and the distribution of
dairy farming. The nomadic Nenets have been reindeer herders for generations and
have therefore not consumed any dairy products. The hypotheses here was that the
prevalence of lactase non-persistence (-13910 C/C genotype) among Nenets people
having four Nenets grandparents is high, while the prevalence among Nenets
originating from ethnically mixed families is lower. Study design The material
was collected in four typical Nenets settlements in the Nenets Autonomous Okrug
in Russia. One-third of the adult Nenets population were invited to answer a
questionnaire and to donate buccal samples for genotyping by a doctor from the
team of medical professionals who make rounds in this area. The total number of
available participants was 177. Methods Genotyping was performed with the
AbiPrism system. We used the method of concordance of grandparents' national
origin to ascribe ethnicity. Results The prevalence of adult-type hypolactasia (
13910 C/C) among Nenets who had four Nenets grandparents was found to be 90%. The
figures among others reporting three, two and one grandparent of Nenets origin
were 72, 60 and 28%, respectively. Conclusion The findings are in accord with the
cultural historical hypothesis.
PMID- 28417766
TI - The best of two worlds: how the Greenland Board of Nutrition has handled
conflicting evidence about diet and health.
AB - The traditional diet in Greenland consists to a large extent of meat and organs
of seal and other marine mammals, which is polluted by POPs and mercury. These
substances are present in the blood of Greenlanders in concentrations well above
international guidelines, and as these contaminants are suspected of having
negative impacts on health, some action should be taken. On the other hand,
traditional food is also an important source of health promoting micronutrients
that are not provided by imported food in sufficient quantities, for example
vitamin D, long chain n-3 fatty acids, and selenium, not to mention the
traditional diet's function as a social glue that is perceived as important for
Inuit identity in Greenland. The proportion of the total diet that comes from
marine mammals is on a constant decrease, and especially children and young
adults consume rather little seal and whale. The traditional food items are
consequently being replaced by imported food, and among the imported food items
several rather unhealthy items are popular, that is carbonated soft drinks with
sugar, sweets, chips and farmed (red) meat with a high content of saturated fat.
Together with a decrease in physical activity, this dietary transition has
resulted in a severe epidemic of overweight and diabetes. In giving advice to the
public, the Greenland Board of Nutrition was therefore faced with the challenge
to retain the benefits of the traditional diet while minimizing the contaminant
exposure, and at the same time to counteract the effects of poor quality imported
food. The Board tried to balance the known and suspected positive and negative
aspects of the total diet in relation not only to physical health but to general
wellbeing, and decided on 10 simple recommendations. As the consumption of
traditional food becomes less prominent and as the consumption of food rich in
empty calories increases, the guidelines are continuously revised and updated.
PMID- 28417767
TI - IJCH Enters a New Era.
PMID- 28417768
TI - Vitamin D deficiency among northern Native Peoples: a real or apparent problem?
AB - Vitamin D deficiency seems to be common among northern Native peoples, notably
Inuit and Amerindians. It has usually been attributed to: (1) higher latitudes
that prevent vitamin D synthesis most of the year; (2) darker skin that blocks
solar UVB; and (3) fewer dietary sources of vitamin D. Although vitamin D levels
are clearly lower among northern Natives, it is less clear that these lower
levels indicate a deficiency. The above factors predate European contact, yet pre
Columbian skeletons show few signs of rickets-the most visible sign of vitamin D
deficiency. Furthermore, because northern Natives have long inhabited high
latitudes, natural selection should have progressively reduced their vitamin D
requirements. There is in fact evidence that the Inuit have compensated for
decreased production of vitamin D through increased conversion to its most active
form and through receptors that bind more effectively. Thus, when diagnosing
vitamin D deficiency in these populations, we should not use norms that were
originally developed for European-descended populations who produce this vitamin
more easily and have adapted accordingly. 1Published 'ahead-of-print' 10 November
2011 (at www.ijch.fi ) in accordance with previous publisher's routines.
PMID- 28417769
TI - Innovative primary care delivery in rural Alaska: a review of patient encounters
seen by community health aides.
AB - BACKGROUND: For more than 50 years, Community Health Aides and Community Health
Practitioners (CHA/Ps) have resided in and provided care for the residents of
their villages. OBJECTIVES: This study is a systematic description of the
clinical practice of primary care health workers in rural Alaska communities.
This is the first evaluation of the scope of health problems seen by these lay
health workers in their remote communities. STUDY DESIGN: Retrospective
observational review of administrative records for outpatient visits seen by
CHA/Ps in 150 rural Alaska villages (approximate population 47,370). METHODS:
Analysis of electronic records for outpatient visits to CHA/Ps in village clinics
from October 2004 through September 2006. Data included all outpatient visits
from the Indian Health Service National Patient Information Reporting System.
Descriptive analysis included comparisons by region, age, sex, clinical
assessment and treatment. RESULTS: In total 272,242 visits were reviewed. CHA/Ps
provided care for acute, chronic, preventive, and emergency problems at 176,957
(65%) visits. The remaining 95,285 (35%) of records did not include a diagnostic
code, most of which were for administrative or medication-related encounters. The
most common diagnostic codes were: pharyngitis (11%), respiratory infections
(10%), otitis media (8%), hypertension (6%), skin infections (4%), and chronic
lung disease (4%). Respiratory distress and chest pain accounted for 75%
(n=10,552) of all emergency visits. CONCLUSIONS: CHA/Ps provide a broad range of
primary care in remote Alaskan communities whose residents would otherwise be
without consistent medical care. Alaska's CHA/P program could serve as a health
care delivery model for other remote communities with health care access
challenges. To access the supplementary material to this article: 'NPIRS
Categorical Hierarchy' please see the Supplementary files under Article Tools
online.
PMID- 28417770
TI - Level of selected toxic elements in meat, liver, tallow and bone marrow of young
semi-domesticated reindeer (Rangifer tarandus tarandus L.) from Northern Norway.
AB - Objectives . To gain knowledge on toxic elements in semi-domesticated reindeer
and their distribution in meat, liver, tallow and bone marrow. The correlations
between concentrations in meat and liver, as well as the use of the latter as an
indicator for toxic elements in meat, were also investigated. Study design .
Cross-sectional study on population of semi-domesticated reindeer from 2 northern
Norwegian counties (Finnmark and Nordland). Methods . Semi-domesticated reindeer
carcasses (n = 31) were randomly selected, from which meat, liver, tallow and
bone marrow samples were collected. Selected toxic elements (cadmium, lead,
arsenic, nickel and vanadium) were studied. Results . Liver was the organ with
the highest level of all elements except for nickel, which was highest in bone
marrow. Meat had the lowest levels, whereas levels in tallow and bone marrow were
between those of meat and liver. Concentrations of cadmium, lead and arsenic were
significantly different (p < 0.05) between meat and liver, while only arsenic and
cadmium were significantly correlated in meat (rs=0.71, p < 0.01) and liver
(rs=0.72, p < 0.01). The cadmium level exceeded the European Commission's (EC)
maximum level set for bovine meat and live in 52% of the liver samples (n = 29).
Nevertheless, the estimated monthly cadmium intake from liver of 2.29 ug/kg body
weight was well below the provisional tolerable monthly intake of 25 ug/kg body
weight set by the FAO/WHO Joint Expert Committee on Food Additives. Conclusions .
Based on the measured levels and their relation to the maximum level and to the
provisional tolerable weekly/monthly intake limits, it could be inferred that
consumption of reindeer meat is not associated with any health risk related to
the studied toxic elements for consumers.
PMID- 28417771
TI - The international biological program/human adaptability studies among the Skolt
Sami in Finland (1966-1970).
AB - BACKGROUND: The population is increasingly lighter pigmented moving in a
northward direction in Europe until reaching the Arctic Circle, where the Samis
(Lapps) are clearly more pigmented. METHODS: In 1966-1970, we investigated a
total of 689 subjects in the villages of Sevettijarvi and Nellim, including
persons with mixed Sami and Finnish heritage; of these, 487 (242 males, 245
females) had both parents classified as Skolt Sami. For estimation of the colour
of the iris and hair, international scales were used. For translucency of the
iris, pigmentation of the fundus was estimated in 3 different shades. The length
and type of eyelashes were classified into 3 categories. To our knowledge, a
simultaneous study of the pigmentation of eyebrows, eyelashes and eye fundus at
different ages has not previously been published. RESULTS: The age differences of
iris colour were highly significant. Iris colour in children varied markedly, and
they generally had lighter colours than later in life. Age and sex effects on the
translucency of irises were found. Male irises were more translucent. Fundus
pigmentation was scanty in the youngest age groups, with full pigmentation being
reached at 20 years. Among young individuals hair colour darkens with increasing
age. Eyebrow colour was slightly lighter for both sexes in the youngest age
groups that in older cohorts. Women had longer eyelashes than males. CONCLUSIONS:
The main factor of the lighter skin is a higher ability to synthesize vitamin D,
providing superior protection against rickets. The Skolt Samis are more pigmented
than other Nordic people. In earlier times they had problems with rickets but our
studies did not show any essential symptoms of rickets today. Visual acuity among
Skolt Samis was good. They had lower prevalence of myopia compared to Finns. The
stronger pigmentation of Skolt Samis is probably due to their origin from darker
Eastern populations. Since our investigations were made, the Skolt Samis have
been to a great part mixed with neighbouring populations and scattered throughout
Finland. Even their old language is nowadays used mainly for traditional
purposes. Therefore similar studies could not be performed anymore.
PMID- 28417772
TI - A decade of research in Inuit children, youth, and maternal health in Canada:
areas of concentrations and scarcities.
AB - Inuit Canadians are on average about 20 years younger and have a 10-year lower
life expectancy than other Canadians. While there have been improvements in Inuit
health status over time, significant health disparities still remain. This paper
will review the peer-reviewed literature related to Inuit child, youth, and
maternal health between 2000 and 2010, investigate which thematic areas were
examined, and determine what proportion of the research is related to each group.
Establishing areas of research concentrations and scarcities may help direct
future research where it is needed. We followed a systematic literature review
and employed peer-reviewed research literature on child, youth, and maternal
health which were selected from 3 sources, MEDLINE, CINAHL, and the Circumpolar
Health Bibliographic Database. The resulting references were read, and summarized
according to population group and thematic area. The thematic areas that emerged
by frequency were: infectious disease; environment/environmental exposures;
nutrition; birth outcomes; tobacco; chronic disease; health care; policy, human
resources; interventions/programming; social determinants of health; mental
health and wellbeing; genetics; injury; and dental health. The 72 papers that met
the inclusion criteria were not mutually exclusive with respect to group studied.
Fifty-nine papers (82%) concerned child health, 24 papers (33%) youth health, and
58 papers (81%) maternal health. The review documented high incidences of illness
and significant public health problems; however, in the context of these issues,
opportunities to develop research that could directly enhance health outcomes are
explored.
PMID- 28417773
TI - Cancer patterns in Inuit Nunangat: 1998-2007.
AB - Objectives . To compare cancer incidence patterns between residents of Inuit
Nunangat and the rest of Canada. Study design . Cancer cases were geographically
linked to either Inuit Nunangat or the rest of Canada using postal codes or other
geographic information. Population estimates were derived from the 2001 and 2006
censuses. Methods . Cancer cases were combined from 1998 to 2007 for Inuit
Nunangat and the rest of Canada. Age-standardised incidence rates were calculated
for all site cancers and sub-sites by sex. Standardised rate ratios between these
2 areas were calculated for all site cancers and sub-sites. Results . The age
standardised incidence rate for all cancer sites (1998-2007) was 14% lower for
the Inuit Nunangat male population and 29% higher for the female population by
comparison to the rest of Canada. Cancers of the nasopharynx, lung and bronchus,
colorectal, stomach (males), and kidney and renal pelvis (females), were elevated
in the Inuit Nunangat population compared to the rest of Canada, whereas prostate
and female breast cancers were lower in the Inuit Nunangat population.
Conclusions . Cancers with potentially modifiable risk factors, such as buccal
cavity and pharynx, nasopharynx, lung and bronchus, and colorectal cancer were
elevated in the Inuit Nunangat population compared to the rest of Canada. Besides
greater smoking prevalence within Inuit Nunangat by comparison to the rest of
Canada, distinct socioeconomic characteristics between respective area
populations including housing, and income may have contributed to incidence
differentials. This study demonstrated that a geographic approach can be used in
cancer surveillance when populations of interest are spatially distinguishable,
and reside across distinct jurisdictions whose combined cancer registries will
not completely provide information to identify the population of interest.
PMID- 28417774
TI - The health of young Swedish Sami with special reference to mental health.
AB - OBJECTIVES: To investigate the health of young Sami in Sweden and the
relationship between health and experience of negative societal treatment due to
ethnicity, as well as socio-demographic background factors. STUDY DESIGN: Cross
sectional population-based questionnaire study. METHODS: A total of 876 persons
aged 18-28 and involved in Sami associated activities were addressed, and 516
(59%) responded to a questionnaire investigating physical health, mental health,
and stress. Data were analyzed with regard to gender, family situation,
occupation, education, enculturation factors and experience of being badly
treated because of ethnicity. RESULTS: A majority of the young Sami reported
feeling healthy, but close to half of the group reported often having worries,
often forgetting things and often experiencing lack of time for doing needed
things. Women and those living alone reported a more negative health.
Furthermore, half of the group had perceived bad treatment because of Sami
ethnicity, and this was negatively associated with some aspects of mental health.
CONCLUSION: The young Sami had a rather good and possibly slightly better health
than other young Swedes, except regarding worries and stress. A high degree of
bad treatment due to Sami ethnicity and its negative association with health, may
partly explain the high degree of some health problems.
PMID- 28417775
TI - Breast cancer in the Arctic - changes over the past decades.
AB - The purpose of this study is to review the current literatures on breast cancer
(BC) in the Arctic, especially the trends in incidence during the last decades
and the possible explanations. The design of this study is a literature review.
The scientific literature concerning BC were reviewed, especially focusing on the
Arctic and the special conditions that exist in this region. Breast cancer
incidence is increasing all over the world, including in the Arctic. The enormous
transition in health conditions and lifestyle in the Arctic might be contributing
to the known risk factors. In Greenland, the age at menarche has diminished by 3
years during the course of 100 years, and the number of children per women as
well as the duration of breastfeeding is decreasing. Obesity and intake of
saturated fat is increasing and the intake of traditional food rich in
unsaturated fat and vitamin D decreasing. Smoking and alcohol consumption in the
Arctic has been relatively high but is now decreasing. More focus on genetic
susceptibility in relation to BC has identified the specific BRCA1 founder
mutation in the Greenlandic population, which might appear to be an important
risk factor. However, the known established risk factors alone cannot account for
the increasing trend observed. Studies suggest that environmental contaminants
such as persistent organic pollutants (POPs) including perfluorinated compounds
increase the risk of BC possibly in conjunction with certain genetic
polymorphisms involved in carcinogen activation. The lipophilic POPs such as
polychlorinated biphenyls and organochlorine pesticides are found at very high
levels in the Arctic population. Several factors can explain the increasing
incidence of BC in the Arctic. The transition in lifestyle and health conditions
unfortunately increases the known risk factors of BC. Moreover, the population of
the Arctic might show up to be especially vulnerable because of the contemporary
high burden of POPs and genetic susceptibility.
PMID- 28417776
TI - Suicidal ideation among Metis adult men and women - associated risk and
protective factors: findings from a nationally representative survey.
AB - OBJECTIVE: To determine the prevalence of suicidal ideation among Metis men and
women (20-59 years) and identify its associated risk and protective factors using
data from the nationally representative Aboriginal Peoples Survey (2006). STUDY
DESIGN: Secondary analysis of previously collected data from a nationally
representative cross-sectional survey. RESULTS: Across Canada, lifetime suicidal
ideation was reported by an estimated 13.3% (or an estimated 34,517 individuals)
of the total population of 20-to-59-year-old Metis. Of those who ideated, 46.2%
reported a lifetime suicide attempt and 6.0% indicated that they had attempted
suicide in the previous 12 months. Prevalence of suicidal ideation was higher
among Metis men than in men who did not report Aboriginal identity in examined
jurisdictions. Metis women were more likely to report suicidal ideation compared
with Metis men (14.9% vs. 11.5%, respectively). Metis women and men had some
common associated risk and protective factors such as major depressive episode,
history of self-injury, perceived Aboriginal-specific community issues, divorced
status, high mobility, self-rated thriving health, high self-esteem and positive
coping ability. However, in Metis women alone, heavy frequent drinking, history
of foster care experience and lower levels of social support were significant
associated risk factors of suicidal ideation. Furthermore, a significant
interaction was observed between social support and major depressive episode.
Among Metis men, history of ever smoking was the sole unique associated risk
factor. CONCLUSION: The higher prevalence of suicidal ideation among Metis women
compared with Metis men and the observed gender differences in associations with
some associated risk and protective factors suggest the need for gender
responsive programming to address suicidal ideation.
PMID- 28417778
TI - The State of the Journal.
PMID- 28417777
TI - Healthcare use for acute gastrointestinal illness in two Inuit communities:
Rigolet and Iqaluit, Canada.
AB - Background The incidence of self-reported acute gastrointestinal illness (AGI) in
Rigolet, Nunatsiavut, and Iqaluit, Nunavut, is higher than reported elsewhere in
Canada; as such, understanding AGI-related healthcare use is important for
healthcare provision, public health practice and surveillance of AGI. Objectives
This study described symptoms, severity and duration of self-reported AGI in the
general population and examined the incidence and factors associated with
healthcare utilization for AGI in these 2 Inuit communities. Design Cross
sectional survey data were analysed using multivariable exact logistic regression
to examine factors associated with individuals' self-reported healthcare and over
the-counter (OTC) medication utilization related to AGI symptoms. Results In
Rigolet, few AGI cases used healthcare services [4.8% (95% CI=1.5-14.4%)]; in
Iqaluit, some cases used healthcare services [16.9% (95% CI=11.2-24.7%)]. Missing
traditional activities due to AGI (OR=3.8; 95% CI=1.18-12.4) and taking OTC
medication for AGI symptoms (OR=3.8; 95% CI=1.2-15.1) were associated with
increased odds of using healthcare services in Iqaluit. In both communities, AGI
severity and secondary symptoms (extreme tiredness, headache, muscle pains,
chills) were significantly associated with increased odds of taking OTC
medication. Conclusions While rates of self-reported AGI were higher in Inuit
communities compared to non-Inuit communities in Canada, there were lower rates
of AGI-related healthcare use in Inuit communities compared to other regions in
Canada. As such, the rates of healthcare use for a given disease can differ
between Inuit and non-Inuit communities, and caution should be exercised in
making comparisons between Inuit and non-Inuit health outcomes based solely on
clinic records and healthcare use.
PMID- 28417779
TI - How are your berries? Perspectives of Alaska's environmental managers on trends
in wild berry abundance.
AB - Background Wild berries are a valued traditional food in Alaska. Phytochemicals
in wild berries may contribute to the prevention of vascular disease, cancer and
cognitive decline, making berry consumption important to community health in
rural areas. Little was known regarding which species of berries were important
to Alaskan communities, the number of species typically picked in communities and
whether recent environmental change has affected berry abundance or quality.
Objective To identify species of wild berries that were consumed by people in
different ecological regions of Alaska and to determine if perceived berry
abundance was changing for some species or in some regions. Design We asked
tribal environmental managers throughout Alaska for their views on which among 12
types of wild berries were important to their communities and whether berry
harvests over the past decade were different than in previous years. We received
responses from 96 individuals in 73 communities. Results Berries that were
considered very important to communities differed among ecological regions of
Alaska. Low-bush blueberry (Vaccinium uliginosum and V. caespitosum), cloudberry
(Rubus chamaemorus) and salmonberry (Rubus spectabilis) were most frequently
identified as very important berries for communities in the boreal, polar and
maritime ecoregions, respectively. For 7 of the 12 berries on the survey, a
majority of respondents indicated that in the past decade abundance had either
declined or become more variable. Conclusions Our study is an example of how
environmental managers and participants in local observer networks can report on
the status of wild resources in rural Alaska. Their observations suggest that
there have been changes in the productivity of some wild berries in the past
decade, resulting in greater uncertainty among communities regarding the security
of berry harvests. Monitoring and experimental studies are needed to determine
how environmental change may affect berry abundance.
PMID- 28417780
TI - Prevalence of self-reported myocardial infarction in Sami and non-Sami
populations: the SAMINOR study.
AB - Objective Measure the prevalence of self-reported myocardial infarction (SMI) in
Sami and non-Sami populations in rural areas of Norway, and explore whether
possible ethnic differences could be explained by established cardiovascular risk
factors. Design Cross-sectional population-based study. Methods A health survey
was conducted in 2003-2004 in areas with Sami and non-Sami populations (SAMINOR).
The response rate was 60.9%. Information concerning lifestyle was collected by 2
self-administrated questionnaires, and clinical examinations provided
anthropometric measurements, and data on blood pressure and lipid levels. Results
The total number for the subsequent analysis was 15,206 men and women aged 36-79
years (born 1925-1968). Sex-specific analyses revealed no ethnic difference in
SMI. In terms of the most important risk factors such as smoking, blood pressure,
and lipid levels, no or only trivial ethnic differences were found in both women
and men. Conclusion In this study, we found no difference in SMI between Sami and
non-Sami in rural areas in Norway. The similar risk profile is the most plausible
explanation; similar living conditions and close interaction between the ethnic
groups may explain this.
PMID- 28417782
TI - The process of developing a community-based research agenda with lesbian, gay,
bisexual, transgender and queer youth in the Northwest Territories, Canada.
AB - Background Youth in Canada's Northwest Territories (NWT) experience sexual and
mental health disparities. Higher rates of sexual and mental health concerns
among lesbian, gay, bisexual, transgender and queer (LGBTQ) youth in comparison
with heterosexual and cisgender peers have been associated with stigma and
discrimination. Although LGBTQ youth in the NWT are situated at the nexus of
Northern and LGBTQ health disparities, there is little known about their health,
well-being and experiences of stigma. This short communication discusses the
process of developing a LGBTQ youth community-based research programme in the
NWT. Methods We developed an interdisciplinary research team of LGBTQ and allied
young adults, including indigenous and non-indigenous researchers, community
organisers and service providers in the NWT. We conducted meetings in Yellowknife
with LGBTQ youth (n=12) and key stakeholders (n=15), including faculty, students,
community groups and health and social service providers. Both meetings included
LGBTQ and allied participants who were LGBTQ, indigenous, youth and persons at
the intersection of these identities. Results LGBTQ youth participants discussed
community norms that devalued same sex identities and stigma surrounding LGBTQ
specific services and agencies. Stigma among LGBT youth was exacerbated for youth
in secondary schools, gender non-conforming and transgender youth and young gay
men. In the stakeholder meeting, service providers discussed the importance of
integrating LGBTQ issues in youth programmes, and LGBTQ community groups
expressed the need for flexibility in service delivery to LGBTQ youth.
Stakeholders identified the need to better understand the needs of indigenous
LGBTQ youth in the NWT. Conclusions Community-based LGBTQ groups, researchers and
health and social service providers are interested in addressing LGBTQ youth
issues in the NWT. The emergence of LGBTQ community building, support groups and
activism in Northern Canada suggests that this is an opportune time to explore
LGBTQ youth health.
PMID- 28417781
TI - Undesirable financial effects of head and neck cancer radiotherapy during the
initial treatment period.
AB - Background Healthcare cost and reforms are at the forefront of international
debates. One of the current discussion themes in oncology is whether and how
patients' life changes due to costs of cancer care. In Norway, the main part of
the treatment costs is supported by general taxpayer revenues. Objectives The
objective of this study was to clarify whether head and neck cancer patients
(n=67) in northern Norway experienced financial health-related quality of life
(HRQOL) deterioration due to costs associated with treatment. Design HRQOL was
examined by the European Organization for Research and Treatment of Cancer
(EORTC) QLQ-C30 in the beginning and in the end of radiation treatment in
patients treated at the University Hospital in Northern Norway. Changes in
financial HRQOL were calculated and compared by paired sample T-tests. Multiple
regression analyses were used to examine correlations among gender, marital
status, age and treatment with or without additional chemotherapy and changes in
the HRQOL domain of financial difficulties. Results The majority of score results
at both time points were in the lower range (mean 15-25), indicating limited
financial difficulties. We observed no statistically significant differences by
gender, marital status and age. Increasing financial difficulties during
treatment were reported by male patients and those younger than 65, that is,
patients who were younger than retirement age. The largest effect was seen in
singles. However, differences were not statistically significant. Conclusions
During the initial phase of the disease trajectory, no significant increase in
financial difficulties was found. This is in line with the aims of the Norwegian
public healthcare model. However, long-term longitudinal studies should be
performed, especially with regard to the trends we observed in single, male and
younger patients.
PMID- 28417783
TI - Digital storytelling: a tool for health promotion and cancer awareness in rural
Alaskan communities.
AB - Background The purpose of this study was to learn community members' perspectives
about digital storytelling after viewing a digital story created by a Community
Health Aide/Practitioner (CHA/P). Methods Using a qualitative research design, we
explored digital storytelling likeability as a health-messaging tool, health
information viewers reported learning and, if viewing, cancer-related digital
stories facilitated increased comfort in talking about cancer. In addition, we
enquired if the digital stories affected how viewers felt about cancer, as well
as if viewing the digital stories resulted in health behaviour change or intent
to change health behaviour. Findings A total of 15 adult community members
participated in a 30-45 minute interview, 1-5 months post-viewing of a CHA/P
digital story. The majority (13) of viewers interviewed were female, all were
Alaska Native and they ranged in age from 25 to 54 years with the average age
being 40 years. Due to the small size of communities, which ranged in population
from 160 to 2,639 people, all viewers knew the story creator or knew of the story
creator. Viewers reported digital stories as an acceptable, emotionally engaging
way to increase their cancer awareness and begin conversations. These
conversations often served as a springboard for reflection, insight, and cancer
prevention and risk-reduction activities.
PMID- 28417784
TI - Whiteboard animation for knowledge mobilization: a test case from the Slave River
and Delta, Canada.
AB - Objective To present the co-creation of a whiteboard animation video, an enhanced
e-storytelling technique for relaying traditional knowledge interview results as
narratives. Design We present a design for translating interview results into a
script and accompanying series of figures, followed by technical steps to create
a whiteboard animation product. Method Our project used content analysis and
researcher triangulation, followed by a collaborative process to develop an
animated video to disseminate research findings. A 13-minute long whiteboard
animation video was produced from a research study about changing environments in
northern Canadian communities and was distributed to local people. Three
challenging issues in the video creation process including communication issues,
technical difficulties and contextual debate were resolved among the supporting
agencies and researchers. Conclusions Dissemination of findings is a crucial step
in the research process. Whiteboard animation video products may be a viable and
culturally-appropriate form of relaying research results back to Indigenous
communities in a storytelling format.
PMID- 28417786
TI - Changing of the guards.
PMID- 28417785
TI - Seasonal variation in affective and other clinical symptoms among high-risk
families for bipolar disorders in an Arctic population.
AB - Background In bipolar disorder (BD), seasonality of symptoms is common and
disturbances in circadian rhythms have been reported. Objectives We identified
high-penetrance families in a geographically restricted area in Northern
Fennoscandia and studied the seasonal variation of clinical symptoms among BD
subjects and their healthy relatives. Design We explored the clinical
characteristics of subjects living in Northern Fennoscandia, with extreme annual
variation in daylight. Among known indigenous high-risk families for BD, we
compared the affected ones (N=16) with their healthy relatives (N=15), and also
included 18 healthy non-related controls from the same geographical area.
Seasonal fluctuation in clinical measures was followed up at the 4 most
demarcated photoperiodic time points of the annual cycle: around the summer
solstice and autumn equinox in 2013, the winter solstice in 2013/2014, and the
spring equinox in 2014. In the baseline, lifetime manic symptoms [Mood Disorder
Questionnaire (MDQ)] and morningness-eveningness questionnaire type (MEQ) were
registered, whereas in the follow-up, depressive [Beck Depression Inventory
(BDI)] and distress [General Health Questionnaire (GHQ-12)] symptoms and alcohol
consumption and sleep were recorded. Results Possibly indicative or statistically
significant differences in symptoms between the affected subjects and their
healthy relatives were the BDI winter (13.3 vs. 2.6, t=-2.51, p=0.022) and spring
scores (12.6 vs. 3.2, t=-1.97, p=0.063) and GHQ winter (4.2 vs. 0.82, t=-2.08,
p=0.052) and spring scores (3.8 vs. 0.82, t=-1.97, p=0.063). Scores were higher
among the affected subjects, exceeding a possibly diagnostic threshold (10 and 3)
at all the time points, and without the notable seasonality which was observed
among the healthy relatives. In the overall population, MDQ and MEQ scores had an
inverse correlation (-0.384, significant at 0.016), indicating increased lifetime
manic behaviour among "the night owl" chronotype subjects. Conclusions In an
Arctic population sample, we found different seasonal fluctuation in mood and
distress symptoms and sleep duration scores between subjects with bipolar
spectrum disorders and their healthy relatives. Despite the relatively small
sample size, the results indicate that the symptoms and signs of BD relate to a
disturbance in seasonal variation. Seasonal variation can be considered as an
interesting endophenotype for BD and a promising target for further genetic
studies.
PMID- 28417787
TI - What students do schools allocate to a cognitive-behavioural intervention?
Characteristics of adolescent participants in Northern Sweden.
AB - Background Adolescents are a vulnerable group when it comes to the risk of
developing depression. Preventing the onset of depressive episodes in this group
is therefore a major public health priority. In the last decades, school-based
cognitive-behavioural interventions have been a common primary prevention
approach. However, evidence on what girls actually are allocated to such
interventions when no researchers are involved is scarce. Objective To explore
how a selective cognitive-behavioural program (Depression In Swedish Adolescents)
developed to prevent depression in adolescents, was implemented in a naturalistic
setting in schools in northern part of Sweden. The focus was on characteristics
of participants allocated to the intervention. Design Cross-sectional baseline
data on depressive symptoms, school environment and socio-economic factors were
collected in 2011 by means of questionnaires in schools in a municipality in the
northern part of Sweden. Intervention participants were identified in a follow-up
questionnaire in 2012. Students (n=288) included in the analyses were in the ages
of 14-15. Results Sixty-six girls and no boys were identified as intervention
participants. They reported higher levels of depressive symptoms, lower personal
relative affluence, more sexual harassment victimization and less peer support
compared to female non-participants (n=222). Intervention participants were more
likely to attend schools with a higher proportion of low parental education
levels and a lower proportion of students graduating with a diploma. Conclusions
The developers of the intervention originally intended the program to be
universal or selective, but it was implemented as targeted in these schools. It
is important for school administrations to adhere to program fidelity when it
comes to what students it is aimed for. Implications for effectivenss trials of
cognitive-behavioural interventions in the school setting is discussed.
PMID- 28417788
TI - A scoping review of Indigenous suicide prevention in circumpolar regions.
AB - Background Suicide is a serious public health challenge in circumpolar regions,
especially among Indigenous youth. Indigenous communities, government agencies
and health care providers are making concerted efforts to reduce the burden of
suicide and strengthen protective factors for individuals, families and
communities. The persistence of suicide has made it clear that more needs to be
done. Objective Our aim was to undertake a scoping review of the peer-reviewed
literature on suicide prevention and interventions in Indigenous communities
across the circumpolar north. Our objective was to determine the extent and types
of interventions that have been reported during past decade. We want to use this
knowledge to support community initiative and inform intervention development and
evaluation. Design We conducted a scoping review of online databases to identify
studies published between 2004 and 2014. We included articles that described
interventions in differentiated circumpolar Indigenous populations and provided
evaluation data. We retained grey literature publications for comparative
reference. Results Our search identified 95 articles that focused on suicide in
distinct circumpolar Indigenous populations; 19 articles discussed specific
suicide-related interventions and 7 of these described program evaluation methods
and results in detail. The majority of publications on specific interventions
were found in North American countries. The majority of prevention or
intervention documentation was found in supporting grey literature sources.
Conclusion Despite widespread concern about suicide in the circumpolar world and
active community efforts to promote resilience and mental well-being, we found
few recorded programs or initiatives documented in the peer-reviewed literature,
and even fewer focusing specifically on youth intervention. The interventions
described in the studies we found had diverse program designs and content, and
used varied evaluation methods and outcomes. The studies we included consistently
reported that it was important to use community-based and culturally guided
interventions and evaluations. This article summarizes the current climate of
Indigenous circumpolar suicide research in the context of intervention and
highlights how intervention-based outcomes have largely remained outside of peer
reviewed sources in this region of the world.
PMID- 28417789
TI - Suicide in circumpolar regions: an introduction and overview.
AB - This extended editorial introduces the Special Issue on Suicide and Resilience in
Circumpolar Regions, the results of the knowledge synthesis project by an
international research team funded by the Canadian Institutes of Health Research
and endorsed by the Arctic Council. It focuses on the extent and magnitude of the
problem of suicidal behaviours and thoughts from a circumpolar perspective - the
variation across Arctic States and their northern regions, the excess risk among
some indigenous groups and their demographic characteristics. Much remains to be
learned about the design and implementation of youth-focused intervention
programmes, especially in a circumpolar comparative framework.
PMID- 28417790
TI - "We are like lemmings": making sense of the cultural meaning(s) of suicide among
the indigenous Sami in Sweden.
AB - Background Suicide is a widespread problem among indigenous people residing in
the circumpolar Arctic. Though the situation among the indigenous Sami in
northern Scandinavia is better than among some other indigenous people, suicide
is still regarded as a major public health issue. To adapt prevention strategies
that are culturally attuned one must understand how suicide is understood within
context. That is, the cultural meaning(s) of suicide. Objective To explore and
make sense of the cultural meaning(s) of suicide among Sami in Sweden. Design
Open-ended focus group discussions (FGDs) on the topic "suicide among Sami" were
carried out in 5 Sami communities in Sweden, with in total 22 strategically
selected Sami participants. FGDs were recorded, transcribed verbatim and analyzed
through employing content analysis. Results From the FGDs 4 themes emerged
including "The Sami are fighting for their culture and the herders are in the
middle of the fight," "Suicide as a consequence of Sami losing (or having lost)
their identity," "A wildfire in the Sami world" and "Difficult to get help as a
Sami." Conclusions Findings indicate that Sami in Sweden make sense of suicide in
relation to power and identity within a threatened Sami cultural context. Suicide
is then understood as an act that takes place and makes sense to others when a
Sami no longer has the power to maintain a Sami identity, resulting in being
disconnected from the Sami world and placed in an existential void where suicide
is a solution. The findings are useful in development of culturally attuned
suicide prevention among Sami in Sweden.
PMID- 28417791
TI - Effect evaluation of a heated ambulance mattress-prototype on thermal comfort and
patients' temperatures in prehospital emergency care - an intervention study.
AB - Background The ambulance milieu does not offer good thermal comfort to patients
during the cold Swedish winters. Patients' exposure to cold temperatures combined
with a cold ambulance mattress seems to be the major factor leading to an overall
sensation of discomfort. There is little research on the effect of active heat
delivered from underneath in ambulance care. Therefore, the aim of this study was
to evaluate the effect of an electrically heated ambulance mattress-prototype on
thermal comfort and patients' temperatures in the prehospital emergency care.
Methods A quantitative intervention study on ambulance care was conducted in the
north of Sweden. The ambulance used for the intervention group (n=30) was
equipped with an electrically heated mattress on the regular ambulance stretcher
whereas for the control group (n=30) no active heat was provided on the
stretcher. Outcome variables were measured as thermal comfort on the Cold
Discomfort Scale (CDS), subjective comments on cold experiences, and finger, ear
and air temperatures. Results Thermal comfort, measured by CDS, improved during
the ambulance transport to the emergency department in the intervention group
(p=0.001) but decreased in the control group (p=0.014). A significant higher
proportion (57%) of the control group rated the stretcher as cold to lie down
compared to the intervention group (3%, p<0.001). At arrival, finger, ear and
compartment air temperature showed no statistical significant difference between
groups. Mean transport time was approximately 15 minutes. Conclusions The use of
active heat from underneath increases the patients' thermal comfort and may
prevent the negative consequences of cold stress.
PMID- 28417792
TI - Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation
population with endemic tuberculosis.
AB - Background Canadian First Nation populations have experienced endemic and
epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host
defence peptide LL-37 is known to enhance control of pathogens such as
Mycobacterium tuberculosis. Objective Evaluate associations between serum levels
of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation
participants (N = 34) and assess correlations with single nucleotide
polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding
protein (VDBP). Design Venous blood was collected from all participants at
baseline (winter and summer) and in conjunction with taking vitamin D supplements
(1,000 IU/day) (winter and summer). Samples were analysed using ELISA for
concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were
genotyped. Results Circulating levels of 25(OH)D were not altered by vitamin D
supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs
did not correlate with serum concentrations of 25(OH)D, but LL-37 levels
significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR
SNP Bsm1 T/T genotypes. Conclusions Our findings suggest that vitamin D
supplementation may not be beneficial as an intervention to boost innate immune
resistance to M. tuberculosis in the Dene population.
PMID- 28417793
TI - Guideline concordant detection and management of depression among Alaska Native
and American Indian people in primary care.
AB - Background A tribal health organization in Alaska implemented a primary care
depression screening, detection and management initiative amongst 55,000 Alaska
Native/American Indian people (AN/AIs). Objectives (a) To describe the proportion
of AN/AIs screening positive for depression with depression noted or diagnosed
and proportion with guideline concordant management and (b) to assess whether
management varied by patient and provider factors. Research design Secondary
analysis of electronic and paper medical record information of 400 AN/AIs.
Measures Provider variables, patient demographics and patient clinical factors
were electronically queried. Manual chart audits assessed depression notation,
diagnoses and management within 12 weeks of positive screening. Multilevel
ordinal logistic modelling assessed management by patient and provider factors.
Results A depression diagnosis was present in 141 (35%) charts and 151 (38%) had
depressive symptoms noted. Detection was higher among AN/AIs with moderate and
severe depression (p<0.001). In total, 258 patients (66%) received guideline
concordant management, 32 (8%) had some management, and 110 (28%) received no
management. Younger patient age and increased provider tenure increased odds of
management. Conclusions Most AN/AIs screening positive for depression received
initial guideline concordant management. Additional outreach to older patients
and additional support for providers newer to practices appears warranted.
PMID- 28417794
TI - Assessing health care in Canada's North: what can we learn from national and
regional surveys?
AB - Background Health surveys are a rich source of information on a variety of health
issues, including health care. Objectives This article compares various national
and regional surveys in terms of their geographical coverage with respect to the
Canadian North, especially their Aboriginal population, and the comparability of
the survey contents relating to health care. Methods Three surveys were selected
as providing some information on health care, with separate estimates for the
North and its Aboriginal populations. They are the Canadian Community Health
Survey (CCHS), Aboriginal Peoples Survey (APS) and the First Nations Regional
Health Survey (RHS). Results Different surveys focus on different categories of
Aboriginal people, and no single survey has covered all categories of Aboriginal
people in the North consistently. RHS is targeted at the on-reserve First Nations
population only. APS and CCHS sample the off-reserve First Nations population as
well as Metis and Inuit. To achieve adequate sample size for North-South
comparisons and comparisons among Aboriginal groups within the North, several
cycles of the biennial/annual CCHS can be merged, producing a large data set with
consistent coverage of topics using comparable questions. The content areas of
the 3 surveys can be broadly categorized as health status, health determinants
and health care. Substantial variation exists across surveys in the domains
covered. There are also changes over time in terms of definitions, questions and
even basic concepts. The available health care content of the 3 surveys focus on
access to different types of health services, contact with different categories
of health professionals, unmet health needs and the use of preventive services.
Many important dimensions of health care are not covered. Not all these basic
indicators are available for the North or its Aboriginal populations. Conclusions
A comprehensive survey of health care in the North with sufficient sample size to
provide reliable estimates for its subpopulations - urban and remote, Aboriginal
and non-Aboriginal, and First Nations, Inuit and Metis - would provide useful
information to decision-makers and service providers. Analytical studies can also
be conducted to investigate the correlations and interactions among health
status, health determinants and health care and assess whether such relationships
differ among the different population groups.
PMID- 28417795
TI - Sexual and reproductive health in Greenland: evaluation of implementing sexual
peer-to-peer education in Greenland (the SexInuk project).
AB - Background For decades, the rates of sexually transmitted infections (STIs), such
as gonorrhoea, chlamydia and syphilis, have increased in Greenland, especially
within the young age groups (15-29 years). From 2006 to 2013, the number of
abortions has been consistent with approximately 800-900 abortions per year in
Greenland, which is nearly as high as the total number of births during the same
period. Previous studies in Greenland have reported that knowledge about sexual
health is important, both as prevention and as facilitator to stop the increasing
rates of STIs. A peer-to-peer education programme about sexual health requires
adaption to cultural values and acceptance among the population and government in
order to be sustainable. Objective Formative evaluation of a voluntary project
(SexInuk), in relation to peer-to-peer education with focus on sexual health. Two
workshops were conducted in Nuuk, Greenland, to recruit Greenlandic students.
Design Qualitative design with focus group interviews (FGIs) to collect
qualitative feedback on feasibility and implementation of the project.
Supplemented with a brief questionnaire regarding personal information (gender,
age, education) and questions about the educational elements in the SexInuk
project. Eight Greenlandic students, who had completed one or two workshops, were
enrolled. Results The FGIs showed an overall consensus regarding the need for
improving sexual health education in Greenland. The participants requested more
voluntary educators, to secure sustainability. The articulation of taboo topics
in the Greenlandic society appeared very important. The participants suggested
more awareness by promoting the project. Conclusion Cultural values and language
directions were important elements in the FGIs. To our knowledge, voluntary work
regarding peer-to-peer education and sexual health has not been structurally
evaluated in Greenland before. To achieve sustainability, the project needs
educators and financial support. Further research is needed to investigate how
peer-to-peer education can improve sexual and reproductive health in Greenland.
PMID- 28417796
TI - Patterns of youth injury: a comparison across the northern territories and other
parts of Canada.
AB - Background Injury is the leading cause of death for young people in Canada. For
those living in the northern territories (Yukon, Nunavut, and the Northwest
Territories), injury represents an even greater problem, with higher rates of
injury for people of all ages in northern areas compared with the rest of Canada;
however, no such comparative studies have focussed specifically on non-fatal
injury in youth. Objective To profile and examine injuries and their potential
causes among youth in the northern territories as compared with other parts of
Canada. Design Cross-sectional data from the 2009/2010 Health Behaviour in School
aged Children survey (youth aged 11-15 years) were examined for the Canadian
northern territories and the provinces (n=26,078). Individual survey records were
linked to community-level data to profile injuries and then study possible
determinants via multilevel regression modelling. Results The prevalence of
injury reported by youth was similar in northern populations and other parts of
Canada. There were some minimal differences by injury type: northern youth
experienced a greater percentage of neighbourhood (p<0.001) and fighting (p=0.02)
injuries; youth in the Canadian provinces had a greater proportion of sport
related injuries (p=0.01). Among northern youth, female sex (RR=0.87, 95% CI 0.81
0.94), average (RR=0.88, 95% CI 0.80-0.97) or above-average affluence (RR=0.84,
95% CI 0.76-0.91), not being drunk in the past 12 months (RR=0.77, 95% CI 0.69
0.85), not riding an all-terrain vehicle (RR=0.81, 95% CI 0.68-0.97) and not
having permanent road access (RR=0.89, 95% CI 0.80-0.98) were protective against
injury; sport participation increased risk (RR=1.45, 95% CI 1.33-1.59).
Conclusions Patterns of injury were similar across youth from the North and other
parts of Canada. Given previous research, this was unexpected. When implementing
injury prevention initiatives, individual and community-level risk factors are
essential to understand; however, specific positive safety assets that might
exist in different community contexts must also be considered.
PMID- 28417797
TI - Prevalence of self-reported stomach symptoms after consuming milk among
indigenous Sami and non-Sami in Northern- and Mid-Norway - the SAMINOR study.
AB - Objective The main purpose of this work was to identify the prevalence of self
reported stomach symptoms after consuming milk among Sami and non-Sami adults.
Study design A cross-sectional population-based study (the SAMINOR study). Data
were collected by self-administrated questionnaires. Method SAMINOR is a
population-based study of health and living conditions conducted in 24
municipalities in Northern Norway during 2003 and 2004. The present study
included 15,546 individuals aged between 36 and 79, whose ethnicity was
categorized as Sami (33.4%), Kven (7.3%) and Norwegian majority population
(57.2%). Results Sami respondents had a higher prevalence of self-reported
stomach symptoms after consuming milk than the Norwegian majority population. The
reporting was highest among Sami females (27.1%). Consumption of milk and dairy
products (yoghurt and cheese) was high among all the ethnic groups. However,
significantly more Sami than non-Sami never (or rarely) consume milk or cheese,
and individuals who reported stomach symptoms after consuming milk had an
significant lower intake of dairy products than those not reporting stomach
symptoms after consuming dairy products. Sami reported general abdominal pain
more often than the majority population. The adjusted models show a significant
effect of Sami ethnicity in both men and women on self-reported stomach symptoms
after consuming milk. In females, the odds ratio (OR)=1.77 (p=0.001) and in males
OR=1.64 (p=0.001). Conclusion Our study shows that the Sami population reported
more stomach symptoms after consuming milk, suggesting a higher prevalence of
milk intolerance among the Sami population than the Norwegian majority
population.
PMID- 28417798
TI - Ethnic discrimination and health: the relationship between experienced ethnic
discrimination and multiple health domains in Norway's rural Sami population.
AB - Objective Self-reported ethnic discrimination has been associated with a range of
health outcomes. This study builds on previous efforts to investigate the
prevalence of self-reported ethnic discrimination in the indigenous (Sami)
population, and how such discrimination may be associated with key health
indicators. Study design The study relies on data from the 2003/2004 (n=4,389)
population-based study of adults (aged 36-79 years) in 24 rural municipalities of
Central and North Norway (the SAMINOR study). Self-reported ethnic discrimination
was measured using the question: "Have you ever experienced discrimination due to
your ethnic background?" Health indicators included questions regarding
cardiovascular disease, diabetes, chronic muscle pain, metabolic syndrome and
obesity. Logistic regression was applied to examine the relationship between self
reported ethnic discrimination and health outcomes. Results The study finds that
for Sami people living in minority areas, self-reported ethnic discrimination is
associated with all the negative health indicators included in the study.
Conclusion We conclude that ethnic discrimination affects a wide range of health
outcomes. Our findings highlight the importance of ensuring freedom from
discrimination for the Sami people of Norway.
PMID- 28417799
TI - Continuum of care for persons with common mental health disorders in Nunavik: a
descriptive study.
AB - Background Changing Directions, Changing Lives, the Mental Health Strategy for
Canada, prioritizes the development of coordinated continuums of care in mental
health that will bridge the gap in services for Inuit populations. Objective In
order to target ways of improving the services provided in these contexts to
individuals in Nunavik with depression or anxiety disorders, this research
examines delays and disruptions in the continuum of care and clinical, individual
and organizational characteristics possibly associated with their occurrences.
Design A total of 155 episodes of care involving a common mental disorder (CMD),
incident or recurring, were documented using the clinical records of 79 frontline
health and social services (FHSSs) users, aged 14 years and older, living in a
community in Nunavik. Each episode of care was divided into 7 stages: (a)
detection; (b) assessment; (c) intervention; (d) planning the first follow-up
visit; (e) implementation of the first follow-up visit; (f) planning a second
follow-up visit; (g) implementation of the second follow-up visit. Sequential
analysis of these stages established delays for each one and helped identify when
breaks occurred in the continuum of care. Logistic and linear regression analysis
determined whether clinical, individual or organizational characteristics
influenced the breaks and delays. Results More than half (62%) the episodes of
care were interrupted before the second follow-up. These breaks mostly occurred
when planning and completing the first follow-up visit. Episodes of care were
more likely to end early when they involved anxiety disorders or symptoms,
limited FHSS teams and individuals over 21 years of age. The median delay for the
first follow-up visit (30 days) exceeded guideline recommendations significantly
(1-2 weeks). Conclusion Clinical primary care approaches for CMDs in Nunavik are
currently more reactive than preventive. This suggests that recovery services for
those affected are suboptimal.
PMID- 28417800
TI - Time trend by region of suicides and suicidal thoughts among Greenland Inuit.
AB - Background Suicides remain a major public health problem in Greenland. Their
increase coincides with the modernization since 1950. Serious suicidal thoughts
are reported by a significant proportion of participants in countrywide surveys.
Objective To analyze the time trend by region of suicides and suicidal thoughts
among the Inuit in Greenland. Design Data included the Greenland registry of
causes of death for 1970-2011 and 2 cross-sectional health surveys carried out in
1993-1994 and 2005-2010 with 1,580 and 3,102 Inuit participants, respectively.
Results Suicide rates were higher among men than women while the prevalence of
suicidal thoughts was higher among women. Suicide rates for men and women
together increased from 1960 to 1980 and have remained around 100 per 100,000
person-years since then. The regional pattern of time trend for suicide rates
varied with an early peak in the capital, a continued increase to very high rates
in remote East and North Greenland and a slow increase in villages relative to
towns on the West Coast. Suicidal thoughts followed the regional pattern for
completed suicides. Especially for women there was a noticeable increasing trend
in the villages. The relative risk for suicide was highest among those who
reported suicidal thoughts, but most suicides happened outside this high-risk
group. Conclusion Suicide rates and the prevalence of suicidal thoughts remain
high in Greenland but different regional trends point towards an increased
marginalization between towns on the central West Coast, villages and East and
North Greenland. Different temporal patterns call for different regional
strategies of prevention.
PMID- 28417801
TI - Ethical guidelines for Sami research: the issue that disappeared from the
Norwegian Sami Parliament's agenda?
AB - Background In recent decades many indigenous communities, policy makers and
researchers worldwide have criticized the academic community for not being aware
of the specific challenges these communities have faced and still are facing with
regard to research. One result of the decades of discourse in indigenous
communities is the development in many Western countries of indigenously
sensitive ethical research guidelines. In 1997 the Sami Parliament (SP) in Norway
reached a unanimous decision that ethical guidelines for Sami research had to be
drawn up. Such guidelines are however still to be created. Objectives The
objectives of this article are to enquire into what happened to the Norwegian
SP's decision of 1997 and to reflect on why the issue seems to have disappeared
from the SP's agenda. Finally, we consider whether research ethics is to be a
subject for the research community only. Methods A review of parliamentary white
papers on research and SP documents relating to research ethics. Findings The
response to the SP's decision in 1997 took place in two different channels, both
of them national, namely the research ethics channel and the political channel.
Thus, there were actually two parallel processes taking place. In spite of nearly
two decades of reports, the concept of the participation of indigenous
communities in research is still not an integral part of Norwegian ethical
guidelines. Conclusions The issue of indigenously sensitive research ethics seems
to have disappeared from the SP's agenda and the research ethics review system
with regard to Sami research is with minor adjustments the same as when the SP
asked for a revision.
PMID- 28417803
TI - Outbreak of eczema and rhinitis in a group of office workers in Greenland.
AB - Introduction Disturbed indoor climate may in some cases be associated with
illness. In the present paper, we report the results from a thorough
investigation of office workers in Greenland, who developed skin and/or airway
problems after moving into renewed offices. Material and methods In 2009 the
office of the Bank of Greenland had a total renovation of the building, including
new furniture and carpets. Symptoms developed within the first year after moving
back into the renewed buildings. After removal of carpets in the building,
symptoms significantly improved. Workers were examined in 2009 and re-examined in
2013, including clinical examination, patch test and when relevant also skin
prick tests and histamine release test. Isothiazolinones and fumarates, both able
to cause airway as well as skin symptoms, were isolated from carpets before
testing, and included in the test series. Results In total, 32 out of 80 workers
(40%) developed symptoms; 27 reported eczema, 20 rhinitis and 4 urticaria. Eczema
was located on the hands and/or lower arms in 18 workers, on the face in 10
workers and on legs/trunk in 12 workers. After intervention in the office, 22
workers with eczema reported significant improvement, all cases of hand eczema
cleared and 16 workers with rhinitis also improved. Positive patch tests to
carpet extracts were found significantly more frequent in the worker cohort than
in a control group comprising 47 dermatitis patients (p<0.001). Only few workers
reacted with a positive response to skin prick test or in the HR test, no obvious
pattern in reactions was found, and no conclusions can be made from these
reactions. Conclusion The results indicate that the reported symptoms are related
to exposures from the building after renovation in 2009. A specific triggering
exposure could not be identified, although chemicals from the glued carpets are
suspected. The study is an example of a work place investigation, and illustrates
the diversity of symptoms and exposures involved in "Sick Building" cases.
PMID- 28417804
TI - Conceptual understanding of social capital in a First Nations community: a social
determinant of oral health in children.
AB - Objective The purpose of the study was: (a) to better understand the concept of
social capital and its potential role in oral health of children in a First
Nations community and (b) to identify the strengths and resources in terms of
social capital and a health promotion model that the community has at its
disposal to address its oral health issues. Methods In this qualitative case
study, participants were purposively selected in a First Nations community: Seven
individual interviews and two focus groups involving 18 parents/care givers were
selected. Putnam's concept of social capital guided all the interviews. The
interviews were recorded and transcribed verbatim. Thematic analysis was employed
using the NVivo software. Results The community was close-knit and seemed to have
strong moral fibre, which encouraged members to help each other. A strong bonding
social capital was also found among the members, especially inside the clans
(families). A need for improvement in bridging social capital that would help the
community to reach external resources was observed. While members of the
community were actively involved in religious rituals and cultural ceremonies,
more efforts seemed to be required to recruit volunteers for other events or
programs. Active engagement of community members in any program requires that
members be given a voice as well as some ownership of the process. Mobilizing or
building community's social capital can play a role when planning future
interventions. Conclusion A better understanding of social capital may enhance
the community's investment and efforts by reinforcing healthy oral behaviours and
improving access to external resources. With more dynamic collaboration, it may
be possible to create more sustainable community-based oral health promotion
programs.
PMID- 28417805
TI - One Health - a strategy for resilience in a changing arctic.
AB - The circumpolar north is uniquely vulnerable to the health impacts of climate
change. While international Arctic collaboration on health has enhanced
partnerships and advanced the health of inhabitants, significant challenges lie
ahead. One Health is an approach that considers the connections between the
environment, plant, animal and human health. Understanding this is increasingly
critical in assessing the impact of global climate change on the health of Arctic
inhabitants. The effects of climate change are complex and difficult to predict
with certainty. Health risks include changes in the distribution of infectious
disease, expansion of zoonotic diseases and vectors, changing migration patterns,
impacts on food security and changes in water availability and quality, among
others. A regional network of diverse stakeholder and transdisciplinary
specialists from circumpolar nations and Indigenous groups can advance the
understanding of complex climate-driven health risks and provide community-based
strategies for early identification, prevention and adaption of health risks in
human, animals and environment. We propose a regional One Health approach for
assessing interactions at the Arctic human-animal-environment interface to
enhance the understanding of, and response to, the complexities of climate change
on the health of the Arctic inhabitants.
PMID- 28417806
TI - Partnering with Indigenous student co-researchers: improving research processes
and outcomes.
AB - Objective To examine the contribution of student co-researchers to a community
based participatory Photovoice investigation of Indigenous children's food
related lived experience. We examine co-researchers' contributions to the
research process, their role in knowledge co-generation and dissemination, and
factors that fostered research partnership with the teenage co-researchers.
Methods High school students attending a First Nation community school in Canada
were trained as research partners. They contributed to aspects of research
design, conducted interviews with grades 3 and 4 Photovoice participants, and
participated in data analysis and the development of a culturally relevant
photobook. The study was initiated by the community's research committee. It is
informed by critical consciousness theory and the positive youth development
framework. Results Student co-researchers incorporated culturally appropriate
strategies as they interviewed participants. Co-researchers adopted
conversational approaches, built rapport by articulating personal and cultural
connections, and engaged in mentoring and health promotion as they interviewed
participants. They made critical contributions to dissemination by developing
photobook content that promoted the importance of traditional foods and the vital
role of family and community in healthy eating practices. Relationships and
"dialogic" space were important to building partnership with and promoting
capacity development among youth co-researchers. Conclusions Partnership between
university researchers and Indigenous student co-researchers holds great promise
for health promotion in communities. Co-researchers developed research and
leadership skills, gained understanding of health challenges facing their
community, and initiated health and cultural promotion through the project's
Photobook. This investigation supports the powerful potential of student co
researchers to meaningfully contribute to research processes and to build
knowledge that is relevant and credible both within and outside of their
communities. Findings have implications for youth, communities and researchers.
PMID- 28417807
TI - Incident diabetes, hypertension and dyslipidemia in a Manitoba First Nation.
AB - Background Diabetes and diabetes complications are substantially higher among
Canadian First Nations populations compared with the general Canadian population.
However, incidence data using detailed individual assessments from a population
based cohort have not been undertaken. Objective We sought to describe incident
diabetes, hypertension and dyslipidemia in a population-based cohort from a
Manitoba Ojibway First Nation community. Design Study data were from 2 diabetes
screening studies in Sandy Bay First Nation in Manitoba, Canada, collected in
2002/2003 and 2011/2012. The cohort comprised of respondents to both screening
studies (n=171). Health and demographic data were collected using a
questionnaire. Fasting blood samples, blood pressure and anthropometric data were
also collected objectively. Incident diabetes, hypertension and dyslipidemia were
determined. Generalized linear models with Poisson distribution were used to
estimate risk of incident diabetes and cardiometabolic conditions according to
age and sex. Results There were 35 (95% CI: 26, 45) new cases of diabetes among
128 participants without diabetes at baseline (27 or 3.3% per year). While
participants who were 50 years and older at baseline had a significantly higher
risk of incident diabetes at follow-up compared with participants aged 18-29 at
baseline (p=0.012), more than half of the incident cases of diabetes occurred
among participants aged less than 40 at baseline. There were 28 (95% CI: 20, 37)
new cases of dyslipidemia at follow-up among 112 without dyslipidemia at baseline
(25%). There were 36 (95% CI: 31, 42) new cases of hypertension among 104
participants without hypertension at baseline (34.6%). Women had half the risk of
developing hypertension compared with men (p=0.039). Conclusions Diabetes
incidence is very high, and the number of new cases among those younger than 40
is a concern. Additional public health and primary care efforts are needed to
address the diabetes burden in this First Nation community.
PMID- 28417808
TI - Development and evaluation of a support program for prostate cancer survivors in
Alaska.
AB - Background Prostate cancer survivors in Alaska and elsewhere have unmet support
needs. The Men's Prostate Cancer Survivorship Retreat, or "men's retreat," was
developed targeting Alaska Native and non-Native men who were survivors of
prostate cancer. The program brought together survivors in a supportive
environment to discuss and share their experiences. Objective Despite the proven
effectiveness of support groups for improving quality of life for cancer
patients, men typically do not participate in formal support groups. This
descriptive study was conducted to explore the needs of Alaska Native and non
Native prostate cancer survivors and assess satisfaction and acceptability of a
men's cancer survivorship retreat in Alaska. Methods Prostate cancer survivors
(N=80) who attended men's retreats during 2009-2013 were asked to complete a
retreat application and post-retreat evaluation. Comments regarding social
support, helpful and valuable aspects of the retreat including overall
satisfaction were reported. Results A men's retreat with activities that engage
men can be successful for prostate cancer survivors. Many men returned for
successive retreats. After the retreat, 97% of the participants said they would
continue with support activities. Conclusion The men's retreat provides a valued
opportunity for men to interact with other survivors and access information from
health professionals. The results from this study highlight a successful model
for social support and resources specific to male prostate cancer survivors.
PMID- 28417809
TI - Prevalence and molecular characterization of Cryptosporidium spp. and Giardia
duodenalis in diarrhoeic patients in the Qikiqtani Region, Nunavut, Canada.
AB - Background Although the prevalences of infection with the protozoan parasites
Cryptosporidium spp. and Giardia duodenalis in humans appear to be relatively
high in the Canadian North, their transmission patterns are poorly understood.
Objective To determine the detection rate and the molecular characteristics of
Cryptosporidium spp. and Giardia duodenalis in diarrhoeic patients in the
Qikiqtani (Baffin Island) Region of Nunavut, Canada, in order to better
understand the burden of illness and the potential mechanisms of transmission.
Study design/methods Diarrhoeal stool specimens (n=108) submitted to the
Qikiqtani General Hospital for clinical testing were also tested for the presence
of Cryptosporidium spp. and Giardia duodenalis using epifluorescence microscopy
and polymerase chain reaction (PCR). DNA sequencing and restriction fragment
length polymorphism (RFLP) analyses were performed on PCR-positive specimens to
determine the species, genotypes and sub-genotypes of the parasites. Results
Cryptosporidium was detected in 15.7% of the diarrhoeic patients, while Giardia
was detected in 4.6%. DNA sequencing of a fragment of the small subunit rRNA gene
indicated that all of the Cryptosporidium amplicons had a 100% homology to C.
parvum, and a gp60 assay showed that all aligned with C. parvum sub-genotype IIa.
Microsatellite analysis revealed 3 cases of sub-genotype IIaA15G2R1, 2 of
IIaA15G1R and 1 case each of sub-genotypes IIaA16G1R1 and IIaA15R1. For Giardia,
results based on the amplification of both the 16S rRNA gene and the gdh gene
were generally in agreement, and both DNA sequencing and RFLP demonstrated the
presence of the G. duodenalis Assemblage B genotype. Conclusions Both C. parvum
and G. duodenalis Assemblage B were present in human diarrhoeal stool specimens
from Nunavut, which was suggestive of zoonotic transmission, although human-to
human transmission cannot be ruled out. To fully understand the public health
significance of the different Cryptosporidium and Giardia species and genotypes
in diarrhoeic patients, it will be imperative to establish the extent of genetic
diversity within these parasites through comprehensive studies of the molecular
epidemiology of cryptosporidiosis and giardiasis in the Nunavut region.
PMID- 28417810
TI - Approaching Etuaptmumk - introducing a consensus-based mixed method for health
services research.
AB - With the recognized need for health systems' improvements in the circumpolar and
indigenous context, there has been a call to expand the research agenda across
all sectors influencing wellness and to recognize academic and indigenous
knowledge through the research process. Despite being recognized as a distinct
body of knowledge in international forums and across indigenous groups, examples
of methods and theories based on indigenous knowledge are not well documented in
academic texts or peer-reviewed literature on health systems. This paper
describes the use of a consensus-based, mixed method with indigenous knowledge by
an experienced group of researchers and indigenous knowledge holders who
collaborated on a study that explored indigenous values underlying health systems
stewardship. The method is built on the principles of Etuaptmumk or two-eyed
seeing, which aim to respond to and resolve the inherent conflicts between
indigenous ways of knowing and the scientific inquiry that informs the evidence
base in health care. Mixed methods' frameworks appear to provide a framing
suitable for research questions that require data from indigenous knowledge
sources and western knowledge. The nominal consensus method, as a western
paradigm, was found to be responsive to embedding of indigenous knowledge and
allowed space to express multiple perspectives and reach consensus on the
question at hand. Further utilization and critical evaluation of this mixed
methodology with indigenous knowledge are required.
PMID- 28417811
TI - Trajectories of women's homelessness in Canada's 3 northern territories.
AB - Background Repairing the Holes in the Net was a 2-year, multilevel action
research project designed to inform the development of culturally appropriate and
gender-specific services for northern women who are homeless or marginally housed
and who face mental health and substance use concerns. The study was designed to
learn about the barriers and supports experienced by homeless women in the North
when accessing mental health care, shelter, housing and other services; and to
inform the work of northern service providers and policy advocates in a position
to implement adjustments in their praxis. Methods This article describes the
trajectories of women's service access and their ideas for service improvement
from 61 qualitative, semi-structured interviews conducted with homeless women in
Whitehorse, Yukon (YT), Yellowknife, Northwest Territories (NT), and Iqualit,
Nunavut (NU). Results Unresolved trauma, poverty and social exclusion, inability
to find and maintain housing and ineffective services emerged as interconnected
and multifaceted challenges related to women's service engagement. In the face of
these challenges, women displayed significant resilience and resistance, and
offered important ideas for service improvement. Conclusions The 4 interconnected
systemic challenges identified in the research, coupled with specific ideas for
change cited by the resilient homeless women interviewed, offer points of entry
to improve service policy and delivery. Implementing trauma-informed approaches
emerged as a key example of how access to, and quality of, services could be
improved for homeless women in the North.
PMID- 28417812
TI - Air ambulance and hospital services for critically ill and injured in Greenland,
Iceland and the Faroe Islands: how can we improve?
AB - The Nordic Atlantic Cooperation (NORA) is an intergovernmental organization under
the auspices of the Nordic Council of Ministers. The NORA region comprises
Greenland, Iceland, Faroe Islands and western coastal areas of Norway.
Historical, cultural and institutional links bind these nations together in
multiple ways, and regional co-operation has in recent years become a focus of
interest. This commentary addresses air medical services (AMSs) and available
advanced hospital services in the 3 smallest NORA countries challenged sparse
populations, hereafter referred to as the region. It seems likely that
strengthened regional co-operation can help these countries to address common
challenges within health care by exchanging know-how and best practices, pooling
resources and improving the efficiency of care delivery. The 4 largest hospitals
in the region, Dronning Ingrids Hospital in Nuuk (Greenland), Landspitali in
Reykjavik and Sjukrahusid a Akureyri, (both in Iceland) and Landssjukrahusid
Torshavn on the Faroe Islands, have therefore undertaken the project Network for
patient transport in the North-West Atlantic (in Danish: Netvaerk for
patienttransport i Vest-Norden). The goal of the project, and of this article, is
to exchange information and provide an overview of current AMSs and access to
acute hospital care for severely ill or injured patients in the 3 participating
countries. Of equal importance is the intention to highlight the need for
increased regional co-operation to optimize use of limited resources in the
provision of health care services.
PMID- 28417813
TI - Human exposure to soil contaminants in subarctic Ontario, Canada.
AB - Background Chemical contaminants in the Canadian subarctic present a health risk
with exposures primarily occurring via the food consumption. Objective
Characterization of soil contaminants is needed in northern Canada due to
increased gardening and agricultural food security initiatives and the presence
of known point sources of pollution. Design A field study was conducted in the
western James Bay Region of Ontario, Canada, to examine the concentrations of
polychlorinated biphenyls, dichlorodiphenyltrichloroethane and its metabolites
(SigmaDDT), other organochlorines, and metals/metalloids in potentially
contaminated agriculture sites. Methods Exposure pathways were assessed by
comparing the estimated daily intake to acceptable daily intake values. Ninety
soil samples were collected at random (grid sampling) from 3 plots (A, B, and C)
in Fort Albany (on the mainland), subarctic Ontario, Canada. The contaminated
soil samples were analysed by gas chromatography with an electron capture
detector or inductively coupled plasma mass spectrometer. Results The range of
SigmaDDT in 90 soil samples was below the limit of detection to 4.19 mg/kg. From
the 3 soil plots analysed, Plot A had the highest SigmaDDT mean concentration of
1.12 mg/kg, followed by Plot B and Plot C which had 0.09 and 0.01 mg/kg,
respectively. Concentrations of other organic contaminants and metals in the soil
samples were below the limit of detection or found in low concentrations in all
plots and did not present a human health risk. Conclusions Exposure analyses
showed that the human risk was below regulatory thresholds. However, the SigmaDDT
concentration in Plot A exceeded soil guidelines set out by the Canadian Council
of Ministers of the Environment of 0.7 mg/kg, and thus the land should not be
used for agricultural or recreational purposes. Both Plots B and C were below
threshold limits, and this land can be used for agricultural purposes.
PMID- 28417814
TI - Lower respiratory tract infection hospitalizations among American Indian/Alaska
Native children and the general United States child population.
AB - Background The lower respiratory tract infection (LRTI)-associated
hospitalization rate in American Indian and Alaska Native (AI/AN) children aged
<5 years declined during 1998-2008, yet remained 1.6 times higher than the
general US child population in 2006-2008. Purpose Describe the change in LRTI
associated hospitalization rates for AI/AN children and for the general US child
population aged <5 years. Methods A retrospective analysis of hospitalizations
with discharge ICD-9-CM codes for LRTI for AI/AN children and for the general US
child population <5 years during 2009-2011 was conducted using Indian Health
Service direct and contract care inpatient data and the Nationwide Inpatient
Sample, respectively. We calculated hospitalization rates and made comparisons to
previously published 1998-1999 rates prior to pneumococcal conjugate vaccine
introduction. Results The average annual LRTI-associated hospitalization rate
declined from 1998-1999 to 2009-2011 in AI/AN (35%, p<0.01) and the general US
child population (19%, SE: 4.5%, p<0.01). The 2009-2011 AI/AN child average
annual LRTI-associated hospitalization rate was 20.7 per 1,000, 1.5 times higher
than the US child rate (13.7 95% CI: 12.6-14.8). The Alaska (38.9) and Southwest
regions (27.3) had the highest rates. The disparity was greatest for infant (<1
year) pneumonia-associated and 2009-2010 H1N1 influenza-associated
hospitalizations. Conclusions Although the LRTI-associated hospitalization rate
declined, the 2009-2011 AI/AN child rate remained higher than the US child rate,
especially in the Alaska and Southwest regions. The residual disparity is likely
multi-factorial and partly related to household crowding, indoor smoke exposure,
lack of piped water and poverty. Implementation of interventions proven to reduce
LRTI is needed among AI/AN children.
PMID- 28417816
TI - Primary health care accessibility challenges in remote indigenous communities in
Canada's North.
AB - Background Despite many improvements, health disparities between indigenous and
non-indigenous populations in Canada's North persist. While a strong primary
health care (PHC) system improves the health of a population, the majority of
indigenous communities are very remote, and their access to PHC services is
likely reduced. Understanding the challenges in accessing PHC services in these
communities is necessary to improve the health of the population. Objective The
objective of the study was to document and analyze the challenges in accessing
PHC services by indigenous people in remote communities in Canada's Northwest
Territories (NWT) from the perspectives of users and providers of PHC services.
Methods Using explorative, qualitative methods, our study involved 14 semi
structured interviews with PHC service providers (SPs) and service users (SUs) in
5 communities across the NWT which varied according to population, remoteness,
ethnic composition and health care resources. The interview guide was developed
after key informant consultations. Results Both SPs and SUs understood the
constraints in providing equitable access to PHC services in remote communities.
The provision of emergency care was found to be particularly challenging, because
of the lack of qualified staff in the community and the dependence on aeromedical
evacuations. Wider dissemination of first aid skills among community members was
seen to cover some gaps and also increase self-confidence. For non-emergency
care, the need to travel outside the community was generally disliked. All
recognized the need for more preventive services which were often postponed or
delayed because of the overwhelming demand for acute care. As long as services
were provided in a community, the satisfaction was high among SUs. SPs
appreciated the orientation they received and the ability to build rapport with
the community. Conclusions Northern SUs and SPs generally acknowledge the health
consequences of living in remote communities. The generally high level of
satisfaction attests to the overall effectiveness of PHC in the region despite
geographical remoteness. Many improvements could be made in terms of upgrading
the clinical skills of SPs and community members, improving staff retention,
extending the frequency and duration of community visits and providing more
attention to preventive services.
PMID- 28417817
TI - Views on electronic cigarette use in tobacco screening and cessation in an Alaska
Native healthcare setting.
AB - Background American Indian (AI) and Alaska Native (AN) communities confront some
of the highest rates of tobacco use and its sequelae. Methods This formative
research project sought to identify the perspectives of 41 stakeholders
(community members receiving care within the healthcare system, primary care
providers, and tribal healthcare system leaders) surrounding the use of
pharmacogenetics toward tobacco cessation treatment in the setting of an AI/AN
owned and operated health system in south central Alaska. Results Interviews were
held with 20 adult AI/AN current and former tobacco users, 12 healthcare
providers, and 9 tribal leaders. An emergent theme from data analysis was that
current tobacco screening and cessation efforts lack information on electronic
cigarette (e-cigarette) use. Perceptions of the use of e-cigarettes role in
tobacco cessation varied. Conclusion Preventive screening for tobacco use and
clinical cessation counseling should address e-cigarette use. Healthcare provider
tobacco cessation messaging should similarly address e-cigarettes.
PMID- 28417818
TI - Evaluation of the K[Formula: see text]ts'iihtla ("We Light the Fire") Project:
building resiliency and connections through strengths-based creative arts
programming for Indigenous youth.
AB - Background The creative arts - music, film, visual arts, dance, theatre, spoken
word, literature, among others - are gradually being recognised as effective
health promotion tools to empower, engage and improve the health and well-being
in Indigenous youth communities. Arts-based programming has also had positive
impacts in promoting health, mental wellness and resiliency amongst youth.
However, often times the impacts and successes of such programming are not
formally reported on, as reflected by the paucity of evaluations and reports in
the literature. Objective The objective of this study was to evaluate a creative
arts workshop for Tlicho youth where youth explored critical community issues and
found solutions together using the arts. We sought to identify the workshop's
areas of success and challenge. Ultimately, our goal is to develop a community
led, youth-driven model to strengthen resiliency through youth engagement in the
arts in circumpolar regions. Design Using a mixed-methods approach, we conducted
observational field notes, focus groups, questionnaires, and reflective practice
to evaluate the workshop. Four youth and five facilitators participated in this
process overall. Results Youth reported gaining confidence and new skills, both
artistic and personal. Many youth found the workshop to be engaging, enjoyable
and culturally relevant. Youth expressed an interest in continuing their
involvement with the arts and spreading their messages through art to other youth
and others in their communities. Conclusions Engagement and participation in the
arts have the potential to build resiliency, form relationships, and stimulate
discussions for community change amongst youth living in the North.
PMID- 28417819
TI - Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae
strains in Nuuk, Greenland: time to reconsider preventive and treatment
strategies.
AB - Objectives Sexually transmitted infections (STIs), including infections with
Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011,
GC testing has been performed on urine with nucleic acid amplification tests
(NAATs) by strand displacement amplification (Becton Dickinson ProbeTec).
Monitoring of GC antibiotic susceptibility by culture was introduced in Nuuk in
2012. Until 2014, no cases of ciprofloxacin-resistant GC strains were reported.
In this paper, we report the finding of ciprofloxacin-resistant GC and describe
the most recent incidence of GC infections in Greenland. Methods The number of
urine NAATs and culture-positive swabs from January to October 2014 were obtained
from the Central Laboratory at Queens Ingrid's Hospital in Nuuk and stratified on
gender, place and period of testing. Incidence rates were estimated as number of
urine NAAT * (12/10) per 100,000 inhabitants. Men in Nuuk with a positive NAAT
for GC were encouraged to provide a urethral swab for culture and susceptibility
testing. Results From January to October 2014, a total of 5,436 urine GC NAATs
were performed on patients from Nuuk and 9,031 from the rest of Greenland. Of
these, 422 (8%) and 820 (9%) were positive, respectively. From January to August,
6 (15%) cultures from Nuuk were ciprofloxacin resistant while in September and
October, 26 (59%) were ciprofloxacin resistant (p<0.01). In total, 35 (40%) of 88
culture-positive isolates showed ciprofloxacin resistance. GC incidence in Nuuk
was 3,017 per 100,000 inhabitants per year, compared to 2,491 per 100,000
inhabitants per year in the rest of Greenland. Conclusion Within a short period,
a rapid and dramatic change in ciprofloxacin susceptibility among GC strains
isolated in Nuuk was documented and recommendation for first line treatments has
changed. Continued monitoring and rethinking of primary and secondary preventive
initiatives is highly recommended in this high GC incidence setting.
PMID- 28417820
TI - Dietary intakes of expeditioners during prolonged sunlight deprivation in polar
enviroments do not support bone health.
AB - Background Early Antarctic expeditions were plagued by nutrient deficiencies, due
to lack of fresh food and reliance on preserved foods. Modern Antarctic
expeditioners also require provisions to be shipped in, but improved knowledge
and storage options ensure foods are nutritionally sound. Despite this,
nutritional imbalances are observed. Objectives To determine the adequacy of
dietary intake of Antarctic expeditioners, with reference to bone health. Design
Dietary intake was determined on 225 adults (mean age 42+/-11 years, 16% female)
during 12-month deployments at Australian Antarctic stations from 2004 to 2010,
using weighed 3-day food records. Nutrient intake was analysed using FoodWorks.
Foods were divided into the 5 food groups according to the Australian Guide to
Healthy Eating. Results Men consumed below the recommended levels [recommended
daily intake (RDI)/adequate intakes (AI)] of calcium (79+/-42% of RDI, p<0.001),
magnesium (83+/-34% of RDI, p<0.001), potassium (86+/-29% of AI, p<0.001) and
fibre (75+/-30% of AI, p<0.001), and above the upper limit (UL) for sodium (125+/
48% of UL p<0.001), whereas women consumed below the recommended levels of
calcium (68+/-21% of RDI, p<0.001) and iron (73+/-37% of RDI, p<0.001). Vitamin D
intake is not substantial (<150 IU/d). Men consumed more alcohol than women (18+/
24 g/d vs. 10+/-13 g/d, p<0.05), nearer the guideline of <=20 g/d. Men and women
consumed approximately 1 serving of dairy food per day, and 3 of 5 recommended
vegetable servings. Discretionary foods were consumed in excess of recommended.
Conclusions Improving consumption of calcium-rich (dairy) foods better supports
bone health during sunlight deprivation. Increasing vegetable intake to
recommended levels will increase fibre, potassium and magnesium intakes. The
challenge is the logistics of providing these foods throughout the year.
PMID- 28417821
TI - What can we talk about, in which language, in what way and with whom? Sami
patients' experiences of language choice and cultural norms in mental health
treatment.
AB - Background The Sami in Norway have a legal right to receive health services
adapted to Sami language and culture. This calls for a study of the significance
of language choice and cultural norms in Sami patients' encounters with mental
health services. Objectives To explore the significance of language and cultural
norms in communication about mental health topics experienced by Sami patients
receiving mental health treatment to enhance our understanding of linguistic and
cultural adaptation of health services. Methods Data were collected through
individual interviews with 4 Sami patients receiving mental health treatment in
Northern Norway. A systematic text reduction and a thematic analysis were
employed. Findings Two themes were identified: (I) Language choice is influenced
by language competence, with whom one talks and what one talks about.
Bilingualism was a resource and natural part of the participants' lives, but
there were limited possibilities to speak Sami in encounters with health
services. A professional working relationship was placed on an equal footing with
the possibility to speak Sami. (II) Cultural norms influence what one talks
about, in what way and to whom. However, norms could be bypassed, by talking
about norm-regulated topics in Norwegian with health providers. Conclusion Sami
patients' language choice in different communication situations is influenced by
a complexity of social and cultural factors. Sami patients have varying opinions
about and preferences for what they can talk about, in which language, in what
way and with whom. Bilingualism and knowledge about both Sami and Norwegian
culture provide latitude and enhanced possibilities for both patients and the
health services. The challenge for the health services is to allow for and
safeguard such individual variations within the cultural framework of the
patients.
PMID- 28417822
TI - Lifestyle, reproductive factors and food intake in Greenlandic pregnant women:
The ACCEPT - sub-study.
AB - Background In the past decades, Greenland has changed from a hunter society to a
more western lifestyle, causing less intake of traditional food, such as marine
mammals, fish and seabirds. These changes in the living conditions and food
habits might impact the maternal health in Greenland. Objectives To describe
lifestyle, reproductive factors and food intake in Greenlandic pregnant women,
and to assess possible age and geographical differences. Design Cross-sectional
study of 189 Greenlandic pregnant women. Inclusion criteria were >=18 years and
lived >50% of their life in Greenland. Data were collected in 2010-2011, and
information was obtained from lifestyle and food frequency questionnaires. Two
age groups for comparison were given for the pregnant women (<27 years vs. >=27
years) with regard to the median age. Region groups for comparison were West,
Disko Bay, South, North and East. Results Population characteristics showed that
43.3% had pre-pregnancy body mass index (BMI) >25.0 kg/m2, 46.3% were current
smokers in the beginning of their pregnancy and few participants consumed alcohol
during pregnancy. Women <27 years were more in doubt regarding planned
breastfeeding period and consumed more dried fish and fast food. A trend for
higher alcohol intake during pregnancy was found for women >=27 years. The
regional differences showed that women living >50% in North, South and West had a
higher alcohol intake during pregnancy. Women in North had the fewest
breastfeeding plans. Women in Disko Bay had the lowest intake of terrestrial
species. No significant geographical differences were found for intake of marine
mammals or seabirds. Conclusions The present study found relatively high BMI
level and high smoking frequency in Greenlandic pregnant women. Age and region
differences were found for alcohol consumption, breastfeeding plans and food
intake profile. Further research is needed to implement relevant maternal health
intervention programs in Greenland.
PMID- 28417823
TI - Regional differences in renal replacement therapy in northern Norway 2000-2012.
AB - Objective Distance from residence location to a centre for renal replacement
therapy (RRT) may influence patients' quality of life and prognosis. Northern
Norway constitutes 45% of Norway's landmass, but has less than 10% of the
population. Methods In this study, we analysed all patients in northern Norway
consecutively registered in the Norwegian Renal Registry during 2000-2012. A
total of 634 patients (Nordland County 321 patients, Troms County 215 patients
and Finnmark County 98 patients) were investigated. Results There were more
smokers (31% vs. 22%) and patients with diabetes (32% vs. 22%) in Finnmark, but
the difference did not reach statistical significance. Patients undergoing RRT
and living in Finnmark County had a significantly worse outcome (P=0.03). The
median survivals after initiation of RRT were 3.8 years (Finnmark), 6.4 years
(Troms) and 5.4 years (Nordland), respectively. The most common causes of death
were cardiovascular disease (53%), infections (16%), withdrawal from therapy
(15%) and malignancy (13%). In a Cox analysis, age (P<0.0001), diabetes (P=0.008)
and smoking at any time (P<0.004) were individual factors correlated with
inferior prognosis. Conclusion Age, smoking and diabetes were prognostic factors.
Residents of the northernmost county (Finnmark) experienced an inferior
prognosis. Long distance from residence location to hospital may be another
factor, but this could not be documented. Preventive strategies should be
improved.
PMID- 28417824
TI - Adequate vitamin D levels in a Swedish population living above latitude 63
degrees N: The 2009 Northern Sweden MONICA study.
AB - Background Even though vitamin D is mainly produced by exposure to sunlight,
little is known regarding vitamin D levels in populations living in sub-Arctic
areas with little or no daylight during winter. Objective We describe
distributions of vitamin D3 and the prevalence of adequate levels in a population
living above 63 degrees N. Design We sampled 1,622 randomly selected subjects,
aged 25-74 years, between January and May, 2009, as part of the Northern Sweden
MONICA study (69.2% participation rate). By using HPLC, 25(OH) vitamin D3 was
analysed. Levels used for definitions were deficient, D3<25 nmol/l (<10 ng/ml);
insufficient, D3 25-49.9 nmol/l (10-20 ng/ml); and adequate, D3>=50 nmol/l (20
ng/ml). Results Mean (median) level of vitamin D3 was 65.2 (63.6) nmol/l in men
and 71.0 (67.7) nmol/l in women. Adequate levels were found in 79.2%, more often
in women (82.7%) than in men (75.6%). Only 0.7% of the population were vitamin D3
deficient but 23.1% of men and 17.1% of women had insufficient levels. Levels of
vitamin D3 increased with age and insufficient status was most common among those
aged 25-34 years, 41.0% in men and 22.3% in women. If subjects using vitamin D
supplementation are excluded, the population level of D3 is 1-2 nmol/l lower than
in the general population across sex- and age groups. There were no differences
between the northern or the southern parts, between urban or rural living or
according to educational attainment. Those subjects born outside of Sweden or
Finland had lower levels. Conclusion The large majority living close to the
Arctic Circle in Sweden have adequate D3 levels even during the second half of
the dark winter. Subjects with D3 deficiency were uncommon but insufficient
levels were often found among young men.
PMID- 28417825
TI - Incidence of syphilis in Greenland 2010-2014: The beginning of a new epidemic?
AB - Objective To estimate the incidence of syphilis from 2010 to 2014 and to assess
whether contact tracing has been performed. Study design Observational cross
sectional study. Method Data on reported cases were collected from the national
register of the chief medical officer in Greenland. Unreported cases were found
by searching the electronic medical record system for patients who had received
an electronic prescription of benzathine penicillin, doxycycline or tetracycline.
Medical records were reviewed to verify the diagnosis of syphilis and to evaluate
if contact tracing had been performed. Results Ninety-four cases of syphilis (51
males and 43 females) with a median age of 27 years (20-40) were included. The
incidence of syphilis in Greenland has increased from zero cases in 2010 to 95.7
per 100,000 inhabitants in 2014 affecting mainly young people. Contact tracing
was performed in 80.9% (76/94) of the cases. Conclusion Syphilis has re-occurred
in Greenland and a new epidemic may be underway. Sustained awareness of
treatment, contact tracing, monitoring and preventive initiatives are desirable.
PMID- 28417826
TI - Temporal trends of alcohol and drug use among Inuit of Northern Quebec, Canada.
AB - Background Alcohol and drug use is a serious health problem for many indigenous
populations across Canada, including Inuit. The literature on substance use in
these populations is too sparse to devise public health interventions. Objective
The present article portrays alcohol and drug use among Inuit living in Nunavik
(Northern Quebec) between the 1990s and 2000s, and identifies socio-demographic
characteristics related to substance use. Design The Sante Quebec Health Survey
(1992) and the Nunavik Inuit Health Survey Qanuippitaa (2004) served as databases
for this empirical work. Statistical comparisons were made of substance use
variables in the 2 samples. Proportions were compared by chi-square tests
(p<=0.05) with benchmarking of statistics for all of Quebec and, when available,
all of Canada. Results Alcohol and drug use among Inuit increased significantly
between 1992 and 2004, particularly among young adults. Alcohol users consumed
significantly more alcohol per drinking episode than other Canadians in both time
periods. Considerable cannabis use was widespread. In 2004, no significant
differences in frequencies of heavy drinking episodes were observed by gender,
with 60% of drug users consuming alcohol on a regular basis. Conclusions As in
other populations from North America, this study profiles the increase in
substance use among Inuit from Nunavik in the first part of the last 20 years. We
observed distinct substance use patterns among them in comparison to other
Canadians. Such findings, if replicated in the coming years, emphasize the need
for major, culturally-relevant public health interventions in this population.
PMID- 28417827
TI - Fatty acids linked to cardiovascular mortality are associated with risk factors.
AB - Background Although saturated fatty acids (FAs) have been linked to
cardiovascular mortality, it is not clear whether this outcome is attributable
solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether
other risk factors are also associated with FAs. The Western Alaskan Native
population, with its rapidly changing lifestyles, shift in diet from unsaturated
to saturated fatty acids and dramatic increase in cardiovascular disease (CVD),
presents an opportunity to elucidate any associations between specific FAs and
known CVD risk factors. Objective We tested the hypothesis that the specific FAs
previously identified as related to CVD mortality are also associated with
individual CVD risk factors. Methods In this community-based, cross-sectional
study, relative proportions of FAs in plasma and red blood cell membranes were
compared with CVD risk factors in a sample of 758 men and women aged >=35 years.
Linear regression analyses were used to analyze relations between specific FAs
and CVD risk factors (LDL-C, high-density lipoprotein cholesterol, triglycerides,
C-reactive protein, systolic blood pressure, diastolic blood pressure, heart
rate, body mass index, fasting glucose and fasting insulin, 2-hour glucose and 2
hour insulin). Results The specific saturated FAs previously identified as
related to CVD mortality, the palmitic and myristic acids, were adversely
associated with most CVD risk factors, whereas unsaturated linoleic acid (18:2n
6) and the marine n-3 FAs were not associated or were beneficially associated
with CVD risk factors. Conclusions The results suggest that CVD risk factors are
more extensively affected by individual FAs than hitherto recognized, and that
risk for CVD, MI and stroke can be reduced by reducing the intake of palmitate,
myristic acid and simple carbohydrates and improved by greater intake of linoleic
acid and marine n-3 FAs.
PMID- 28417828
TI - Seasonal prevalence and determinants of food insecurity in Iqaluit, Nunavut.
AB - Background Food insecurity is an ongoing problem in the Canadian Arctic. Although
most studies have focused on smaller communities, little is known about food
insecurity in larger centres. Objectives This study aimed to estimate the
prevalence of food insecurity during 2 different seasons in Iqaluit, the
territorial capital of Nunavut, as well as identify associated risk factors.
Designs A modified United States Department of Agriculture Food Security Survey
was applied to 532 randomly selected households in September 2012 and 523 in May
2013. Chi-square tests and multivariable logistic regression were used to examine
potential associations between food security and 9 risk factors identified in the
literature. Results In September 2012, 28.7% of surveyed households in Iqaluit
were food insecure, a rate 3 times higher than the national average, but lower
than smaller Inuit communities in Nunavut. Prevalence of food insecurity in
September 2012 was not significantly different in May 2013 (27.2%). When
aggregating results from Inuit households from both seasons (May and September),
food insecurity was associated with poor quality housing and reliance on income
support (p<0.01). Unemployment and younger age of the person in charge of food
preparation were also significantly associated with food insecurity. In contrast
to previous research among Arctic communities, gender and consumption of country
food were not positively associated with food security. These results are
consistent with research describing high food insecurity across the Canadian
Arctic. Conclusion The factors associated with food insecurity in Iqaluit
differed from those identified in smaller communities, suggesting that
experiences with, and processes of, food insecurity may differ between small
communities and larger commercial centres. These results suggest that country
food consumption, traditional knowledge and sharing networks may play a less
important role in larger Inuit communities.
PMID- 28417831
TI - Hand-Over Time.
PMID- 28417832
TI - Color Vision in Color Display Night Vision Goggles.
AB - INTRODUCTION: Aircrew viewing eyepiece-injected symbology on color display night
vision goggles (CDNVGs) are performing a visual task involving color under highly
unnatural viewing conditions. Their performance in discriminating different
colors and responding to color cues is unknown. METHODS: Experimental laboratory
measurements of 1) color discrimination and 2) visual search performance are
reported under adaptation conditions representative of a CDNVG. Color
discrimination was measured using a two-alternative forced choice (2AFC) paradigm
that probes color space uniformly around a white point. Search times in the
presence of different degrees of clutter (distractors in the scene) are measured
for different potential symbology colors. RESULTS: The discrimination data
support previous data suggesting that discrimination is best for colors close to
the adapting point in color space (P43 phosphor in this case). There were highly
significant effects of background adaptation (white or green) and test color. The
search time data show that saturated colors with the greatest chromatic contrast
with respect to the background lead to the shortest search times, associated with
the greatest saliency. Search times for the green background were around 150 ms
longer than for the white. Desaturated colors, along with those close to a
typical CDNVG display phosphor in color space, should be avoided by CDNVG
designers if the greatest conspicuity of symbology is desired. DISCUSSION: The
results can be used by CDNVG symbology designers to optimize aircrew performance
subject to wider constraints arising from the way color is used in the existing
conventional cockpit instruments and displays.Liggins EP, Serle WP. Color vision
in color display night vision goggles. Aerosp Med Hum Perform. 2017; 88(5):448
456.
PMID- 28417833
TI - Jugular and Portal Vein Volume, Middle Cerebral Vein Velocity, and Intracranial
Pressure in Dry Immersion.
AB - BACKGROUND: The objective was to determine if short term exposure to dry
immersion (DI) results in a cephalic fluid shift similar to what has been
observed with spaceflight. METHODS: Data were collected from 10 individuals at
rest and during the first 2 h of dry immersion. Jugular vein (JV), portal vein
(PV), and thyroid volume were measured using 3D echography. Middle cerebral vein
velocity (MCVv) was determined using transcranial Doppler ultrasound. The
cochlear response to audio stimulation was used to derive an estimate of
intracranial pressure (dICP). RESULTS: After 2 h of DI, there was a significant
increase (mean +/- SD) in JV (2.21 +/- 1.10 mL), PV (1.05 +/- 0.48 mL), and
thyroid (0.428 +/- 0.313 mL) volume. MCVv was also significantly increased with
DI (3.90 +/- 5.03 cm . s-1). There was no change in dICP with DI in part due to
large individual variability. The range of dICP changes appeared to be related to
MCVv, with participants with the largest increase in MCVv also showing increased
dICP. DISCUSSION: The results suggest that DI induces a significant cephalic
fluid shift similar to what is observed with spaceflight. The increased thyroid
volume suggests that cerebral tissue may also be subjected to similar fluid
filtration, with implications for changes in intracranial pressure. However,
despite all participants having an increase in JV and thyroid volume, only half
showed an increase in dICP, suggesting that increased venous pooling alone is not
sufficient to cause increased intracranial pressure.Arbeille P, Avan P, Treffel
L, Zuj K, Normand H, Denise P. Jugular and portal vein volume, middle cerebral
vein velocity, and intracranial pressure in dry immersion. Aerosp Med Hum
Perform. 2017; 88(5):457-462.
PMID- 28417834
TI - Adaptive Changes in the Perception of Fast and Slow Movement at Different Head
Positions.
AB - BACKGROUND: This paper examines the subjective sense of orientation during
asymmetric body rotations in normal subjects. METHODS: Self-motion perception was
investigated in 10 healthy individuals during asymmetric whole-body rotation with
different head orientations. Both on-vertical axis and off-vertical axis
rotations were employed. Subjects tracked a remembered earth-fixed visual target
while rotating in the dark for four cycles of asymmetric rotation (two half
sinusoidal cycles of the same amplitude, but of different duration). RESULTS: The
rotations induced a bias in the perception of velocity (more pronounced with fast
than with slow motion). At the end of rotation, a marked target position error
(TPE) was present. For the on-vertical axis rotations, the TPE was no different
if the rotations were performed with a 30 degrees nose-down, a 60 degrees nose
up, or a 90 degrees side-down head tilt. With off-vertical axis rotations, the
simultaneous activation of the semicircular canals and otolithic receptors
produced a significant increase of TPE for all head positions. DISCUSSIONS: This
difference between on-vertical and off-vertical axis rotation was probably partly
due to the vestibular transfer function and partly due to different adaptation to
the speed of rotation. Such a phenomenon might be generated in different
components of the vestibular system. The adaptive process enhancing the
perception of dynamic movement around the vertical axis is not related to the
specific semicircular canals that are activated; the addition of an otolithic
component results in a significant increase of the TPE.Panichi R, Occhigrossi C,
Ferraresi A, Faralli M, Lucertini M, Pettorossi VE. Adaptive changes in the
perception of fast and slow movement at different head positions. Aerosp Med Hum
Perform. 2017; 88(5):463-468.
PMID- 28417835
TI - Objective vs. Subjective Evaluation of Cognitive Performance During 0.4-MPa Dives
Breathing Air or Nitrox.
AB - BACKGROUND: Divers try to limit risks associated with their sport, for instance
by breathing enriched air nitrox (EANx) instead of air. This double blinded,
randomized trial was designed to see if the use of EANx could effectively improve
cognitive performance while diving. METHODS: Eight volunteers performed two no
decompression dry dives breathing air or EANx for 20 min at 0.4 MPa. Cognitive
functions were assessed with a computerized test battery, including MathProc and
Ptrail. Measurements were taken before the dive, upon arrival and after 15 min at
depth, upon surfacing, and at 30 min postdive. After each dive subjects were
asked to identify the gas they had just breathed. RESULTS: Identification of the
breathing gas was not possible on subjective assessment alone, while cognitive
assessments showed significantly better performance while breathing EANx. Before
the dives, breathing air, mean time to complete the task was 1795 ms for MathProc
and 1905 ms for Ptrail. When arriving at depth MathProc took 1616 ms on air and
1523 ms on EANx, and Ptrail took 1318 ms on air and and 1356 ms on EANx, followed
15 min later by significant performance inhibition while breathing air during the
ascent and the postdive phase, supporting the concept of late dive/postdive
impairment. DISCUSSION: The results suggest that EANx could protect against
decreased neuro-cognitive performance induced by inert gas narcosis. It was not
possible for blinded divers to identify which gas they were breathing and
differences in postdive fatigue between air and EANx diving deserve further
investigation.Germonpre P, Balestra C, Hemelryck W, Buzzacott P, Lafere P.
Objective vs. subjective evaluation of cognitive performance during 0.4-MPa dives
breathing air or nitrox. Aerosp Med Hum Perform. 2017; 88(5):469-475.
PMID- 28417836
TI - Cervical Spine Status of Pilots and Air-Controllers of Airborne Early Warning and
Control Aircraft.
AB - INTRODUCTION: Many countries have developed their own airborne early warning and
control (AEW&C) systems for use in surveying their territorial sky in real time.
However, a review of the literature suggests that no studies have been conducted
to analyze the cervical spine of pilots and air-controllers of AEW&C aircraft.
METHODS: The study subjects were 80 pilots and air-controllers of AEW&C aircraft
with a period of service of > 1 yr and had data on physical examinations, simple
radiographs and functional scores of the axial skeleton, and questionnaires about
lifestyle and working conditions. Information about physical characteristics and
experience of neck pain were collected. Functional scores including the neck
disability index and short-form 36-item health survey were obtained. Radiological
measurements were performed for the C2-7 Cobb angle and degree of forward head
posture. RESULTS: Of the 80 subjects, 33 (41.3%) had experienced neck pain and 63
(78.8%) had impaired cervical lordosis. The results of functional and
radiological evaluations were not significantly different between pilots and air
controllers. In multivariate analysis, only the age was significantly related to
the occurrence of impaired cervical lordosis. However, there were no significant
factors related to the occurrence of neck pain. DISCUSSION: The results of this
study suggest that the working environment of pilots and air-controllers of AEW&C
aircraft has a negative effect on their cervical spine. Age seemed to be the most
significant factor affecting the occurrence of impaired cervical lordosis in
these subjects.Shin YH, Yun C, Han AH. Cervical spine status of pilots and air
controllers of airborne early warning and control aircraft. Aerosp Med Hum
Perform. 2017; 88(5):476-480.
PMID- 28417837
TI - Flight Crew Workload Evaluation Based on the Workload Function Distribution
Method.
AB - BACKGROUND: The minimum flight crew on the flight deck should be established
according to the workload for individual crewmembers. Typical workload measures
consist of three types: subjective rating scale, task performance, and
psychophysiological measures. However, all these measures have their own
limitations. To reflect flight crew workload more specifically and
comprehensively within the flight environment, and more directly comply with
airworthiness regulations, the Workload Function Distribution Method, which
combined the basic six workload functions, was proposed. METHODS: The analysis
was based on the different conditions of workload function numbers. Each
condition was analyzed from two aspects, which were overall proportion and
effective proportion. Three types of approach tasks were used in this study and
the NASA-TLX scale was implemented for comparison. RESULTS: Neither the one
function condition nor the two-function condition had the same results with NASA
TLX. However, both the three-function and the four- to six- function conditions
were identical with NASA-TLX. Further, the significant differences were different
on four to six conditions. The overall proportion was insignificant, while the
effective proportions were significant. DISCUSSION: The results show that the
conditions with one function and two functions seemed to have no influence on
workload, while executing three functions and four to six functions had an impact
on workload. Besides, effective proportions of workload functions were more
precisely compared with the overall proportions to indicate workload, especially
in the conditions with multiple functions.Zheng Y, Lu Y, Jie Y, Fu S. Flight crew
workload evaluation based on the workload function distribution method. Aerosp
Med Hum Perform. 2017; 88(5):481-486.
PMID- 28417838
TI - Transferring Aviation Practices into Clinical Medicine for the Promotion of High
Reliability.
AB - BACKGROUND: Aviation is a classic example of a high reliability organization
(HRO)-an organization in which catastrophic events are expected to occur without
control measures. As health care systems transition toward high reliability,
aviation practices are increasingly transferred for clinical implementation.
METHODS: A PubMed search using the terms aviation, crew resource management, and
patient safety was undertaken. Manuscripts authored by physician pilots and
accident investigation regulations were analyzed. Subject matter experts involved
in adoption of aviation practices into the medical field were interviewed.
RESULTS: A PubMed search yielded 621 results with 22 relevant for inclusion.
Improved clinical outcomes were noted in five research trials in which aviation
practices were adopted, particularly with regard to checklist usage and crew
resource-management training. Effectiveness of interventions was influenced by
intensity of application, leadership involvement, and provision of staff
training. The usefulness of incorporating mishap investigation techniques has not
been established. Whereas aviation accident investigation is highly standardized,
the investigation of medical error is characterized by variation. DISCUSSION: The
adoption of aviation practices into clinical medicine facilitates an evolution
toward high reliability. Evidence for the efficacy of the checklist and crew
resource-management training is robust. Transference of aviation accident
investigation practices is preliminary. A standardized, independent investigation
process could facilitate the development of a safety culture commensurate with
that achieved in the aviation industry.Powell-Dunford N, McPherson MK, Pina JS,
Gaydos SJ. Transferring aviation practices into clinical medicine for the
promotion of high reliability. Aerosp Med Hum Perform. 2017; 88(5):487-491.
PMID- 28417839
TI - Mortality Due to Cardiovascular Disease Among Apollo Lunar Astronauts.
AB - INTRODUCTION: Recent research has postulated increased cardiovascular mortality
for astronauts who participated in the Apollo lunar missions. The conclusions,
however, are based on small numbers of astronauts, are derived from methods with
known weaknesses, and are not consistent with prior research. METHODS: Records
for NASA astronauts and U.S. Air Force astronauts were analyzed to produce
standardized mortality ratios. Lunar astronauts were compared to astronauts who
have never flown in space (nonflight astronauts), those who have only flown
missions in low Earth orbit (LEO astronauts), and the U.S. general population.
RESULTS: Lunar astronauts were significantly older at cohort entry than other
astronaut group and lunar astronauts alive as of the end of 2015 were
significantly older than nonflight astronauts and LEO astronauts. No significant
differences in cardiovascular disease (CVD) mortality rates between astronaut
groups was observed, though lunar astronauts were noted to be at significantly
lower risk of death by CVD than are members of the U.S. general population (SMR =
13, 95% CI = 3-39). DISCUSSION: The differences in age structure between lunar
and nonlunar astronauts and the deaths of LEO astronauts from external causes at
young ages lead to confounding in proportional mortality studies of astronauts.
When age and follow-up time are properly taken into account using cohort-based
methods, no significant difference in CVD mortality rates is observed. Care
should be taken to select the correct study design, outcome definition, exposure
classification, and analysis when answering questions involving rare occupational
exposures.Reynolds RJ, Day SM. Mortality due to cardiovascular disease among
Apollo lunar astronauts. Aerosp Med Hum Perform. 2017; 88(5):492-496.
PMID- 28417840
TI - Emergency Highway Landings in General Aviation and the Possible Role of Media
Reports.
AB - BACKGROUND: To examine the causes and factors of airplane landings on highways
and the dangers to occupants of vehicles on the ground. METHODS: The U.S.
National Transportation Safety Board online database provided 133 accidents
involving a highway landing dating from 2000 to 2013. Supplemental information
was sought in online media archives, which reported on 53 of these accidents.
Collisions with highway-related objects, other options for landing, and witness
accounts were added categories extracted from the narrative statements and media
reports. RESULTS: Highway landings occur mostly due to mechanical failures,
ineffective preflight or in-flight planning, and fuel exhaustion, in addition to
a lack of alternate landing options for a pilot of a fixed-wing aircraft. Most of
the landings (N = 108) lead to minor or no injuries at all. A significant
proportion of 7 out of 19 collisions with powerlines resulted in a fatality, as
opposed to other types of accidents. Collisions with motor vehicles (N = 29)
caused minor (N = 23) and serious (N = 2) injuries to people on the ground. Main
online media archives covered less than half of all accidents (39.8%).
DISCUSSION: While highway landings are not a recommended landing alternative,
mitigation strategies should include a focus on avoiding powerlines and vehicles
on the ground. Unfortunately, online media archives are not yet a consistent
source of information for general aviation accidents.Holzman E, de Voogt A.
Emergency highway landings in general aviation and the possible role of media
reports. Aerosp Med Hum Perform. 2017; 88(5):497-499.
PMID- 28417841
TI - Benign Episodic Unilateral Mydriasis in a Flight Nurse.
AB - BACKGROUND: Benign episodic unilateral mydriasis is one cause of anisocoria. This
phenomenon is thought to be related to an imbalance between the sympathetic and
parasympathetic nervous systems. There is a documented association with
migraines, but asymptomatic cases have also been reported. A challenge with all
cases is the level of investigation required to exclude more sinister causes of
nervous system dysfunction. In a dynamic flight environment, additional
considerations need to be made, such as varying light levels and use of night
vision devices. CASE REPORT: A 27-yr-old woman on deployment to Afghanistan as a
flight nurse presented to the role one clinic with right-sided mydriasis. The
patient denied headache or any history of migraines. A dilated right pupil that
was reactive to light was found on exam. Symptoms and exam findings resolved
shortly after initial presentation. We consulted an ophthalmologist who requested
patient transfer for review. He made a diagnosis of benign episodic unilateral
mydriasis. DISCUSSION: There are a variety of causes for anisocoria. A thorough
history and examination are required to avoid unnecessary investigations that may
not be locally available in the more austere deployed military settings. From an
operational perspective, the decision needs to be made regarding the maintenance
of flight status. Consideration needs to be given to patient care capability when
treating a flight nurse. In cases of rapid resolution such as this, removal from
operational status is not reasonable should a clinician be confident of the
diagnosis.Schiemer A. Benign episodic unilateral mydriasis in a flight nurse.
Aerosp Med Hum Perform. 2017; 88(5):500-502.
PMID- 28417842
TI - Blood-Injection-Injury (B-I-I) Specific Phobia Affects the Outcome of Hypoxic
Challenge Testing.
AB - BACKGROUND: Blood-injection-injury (B-I-I) phobia is capable of producing
inaccurate hypoxic challenge testing results due to anxiety-induced
hyperventilation. CASE REPORT: A 69-yr-old woman with a history of
hypersensitivity pneumonitis, restrictive spirometry, exercise desaturation
requiring supplementary oxygen on mobilizing, reduced DLco, and B-I-I phobia was
referred for hypoxic challenge testing (HCT) to assess in-flight oxygen
requirements. HCT was performed by breathing a 15% FIo2 gas mixture, simulating
the available oxygen in ambient air onboard aircraft pressurized to an equivalent
altitude of 8000 ft. Spo2 fell to a nadir value of 81% during HCT, although it
rapidly increased to 89% during the first of two attempts at blood gas sampling.
A resultant blood gas sample showed an acceptable Po2 outside the criteria for
recommending in-flight oxygen and a reduced Pco2. Entering the nadir Spo2 value
into the Severinghaus equation gives an estimated arterial Po2 of 6 kPa (45
mmHg), which was felt to be more representative of resting values during HCT, and
in-flight oxygen was recommended. DISCUSSION: While hyperventilation is an
expected response to hypoxia, transient rises in Spo2 coinciding with threat of
injury are likely to be attributable to emotional stress-induced
hyperventilation, characteristic of B-I-I specific phobia and expected during the
anticipation of exteroceptive threat, even in normal subjects. In summary, should
excessive hyperventilation be detected during HCT and coincide with transient
increases in Spo2, HCT should be repeated using Spo2 only as a guide to the level
of hypoxemia, and Spo2 maintained using supplementary oxygen in accordance with
alternative methods described in guidelines.Spurling KJ, McGoldrick VP. Blood
injection-injury (B-I-I) specific phobia affects the outcome of hypoxic challenge
testing. Aerosp Med Hum Perform. 2017; 88(5):503-506.
PMID- 28417843
TI - Letter to the Editor re: Hypoxia Occurrence in a Military Aviator Below 3048 m:
Letter.
PMID- 28417844
TI - You're the Flight Surgeon.
AB - McLaughlin CM. You're the flight surgeon: atypical hypothyroid presentation.
Aerosp Med Hum Perform. 2017; 88(5):509-511.
PMID- 28417845
TI - You're the Flight Surgeon.
AB - Chumbley EM. You're the flight surgeon: a case of bilateral leg pain and swelling
in a loadmaster. Aerosp Med Hum Perform. 2017; 88(5):511-515.
PMID- 28417846
TI - Captain Nels O. Monserud and Medical Consideration of the Women Air Force Service
Pilots: An Enduring Legacy.
PMID- 28417847
TI - This Month in Aerospace Medicine History.
PMID- 28417849
TI - Letter From the Editors.
PMID- 28417848
TI - Dynamic range adaptation in primary motor cortical populations.
AB - Neural populations from various sensory regions demonstrate dynamic range
adaptation in response to changes in the statistical distribution of their input
stimuli. These adaptations help optimize the transmission of information about
sensory inputs. Here, we show a similar effect in the firing rates of primary
motor cortical cells. We trained monkeys to operate a brain-computer interface in
both two- and three-dimensional virtual environments. We found that neurons in
primary motor cortex exhibited a change in the amplitude of their directional
tuning curves between the two tasks. We then leveraged the simultaneous nature of
the recordings to test several hypotheses about the population-based mechanisms
driving these changes and found that the results are most consistent with dynamic
range adaptation. Our results demonstrate that dynamic range adaptation is
neither limited to sensory regions nor to rescaling of monotonic stimulus
intensity tuning curves, but may rather represent a canonical feature of neural
encoding.
PMID- 28417850
TI - Guest Editorial.
PMID- 28417851
TI - Nuclear Medicine Techniques in Pediatric Bone Imaging.
AB - An important mandate when imaging pediatric patients is the reduction of
radiation exposure to the lowest possible level consistent with good quality
diagnostic imaging, so individual selection of radiopharmaceutical dosage and
imaging technique is essential. Although the logistics of image acquisition and
the approach to interpretation mirror the more common use in adults, the
challenges of imaging young children typically require greater attention to
patient preparation, positioning, and supervision during imaging, with the use of
parental or family engagement in the procedure, gentle restraint, and
occasionally the need for sedation. Because the normal bone scan appearance
varies dramatically with age as osseous structures mature, it is critical that
the interpreting physician be well versed in the range of normal variability at
each developmental stage. Although routinely employed in the evaluation of
malignancy, radionuclide bone imaging in children is used for a much wider range
of benign disorders than it is typical in adults. In many pediatric nuclear
medicine departments, the evaluation of benign bone disorders represents most
imaging procedures. Common indications include the evaluation of sports injuries,
osteomyelitis, trauma, including suspected child abuse, growth disorders, such as
mandibular condyle asymmetry, and noninfectious processes such as Langerhans cell
histiocytosis. Both planar scintigraphy and SPECT imaging are widely employed,
although the SPECT acquisition time presents a barrier in some age groups, making
shorter planar spot views desirable when feasible. PET bone imaging with 18F
sodium fluoride has been shown useful in a number of pediatric disorders, but may
present issues in young children, as it can require the use of sedation. Despite
this challenge, the higher resolution and resulting better anatomical depiction
of bone anatomy by PET techniques can be very valuable in evaluating small
structures, and current experience suggests a large future role for fluoride PET
imaging.
PMID- 28417852
TI - Nuclear Medicine in Pediatric Nephro-Urology: An Overview.
AB - In the context of ante-natally diagnosed hydronephrosis, the vast majority of
children with a dilated renal pelvis do not need any surgical treatment, as the
dilatation resolves spontaneously with time. Slow drainage demonstrated at Tc-99m
mercaptoacetyltriglycine (MAG3) renography does not necessarily mean obstruction.
Obstruction is defined as resistance to urinary outflow with urinary stasis at
the level of the pelvic-ureteric junction (PUJ) which, if left untreated, will
damage the kidney. Unfortunately this definition is retrospective and not
clinically helpful. Therefore, the identification of the kidney at risk of losing
function in an asymptomatic patient is a major research goal. In the context of
renovascular hypertension a DMSA scan can be useful before and after
revascularisation procedures (angioplasty or surgery) to assess for gain in
kidney function. Renal calculi are increasingly frequent in children. Whilst the
vast majority of patients with renal stones do not need functional imaging, DMSA
scans with SPECT and a low dose limited CT can be very helpful in the case of
complex renal calculi. Congenital renal anomalies such as duplex kidneys,
horseshoe kidneys, crossed-fused kidneys and multi-cystic dysplastic kidneys
greatly benefit from functional imaging to identify regional parenchymal
function, thus directing further management. Positron emission tomography (PET)
is being actively tested in genito-urinary malignancies. Encouraging initial
reports suggest that F-18-fluorodeoxyglucose (FDG) PET is more sensitive than CT
in the assessment of lymph nodal metastases in patients with genito-urinary
sarcomas; an increased sensitivity in comparison to isotope bone scans for
skeletal metastatic disease has also been reported. Further evaluation is
necessary, especially with the promising advent of PET/MRI scanners. Nuclear
Medicine in paediatric nephro-urology has stood the test of time and is opening
up to new exciting developments.
PMID- 28417853
TI - The Role of 18F-FDG-PET/CT in Pediatric Sarcoma.
AB - Considerable debate remains regarding how best to incorporate 18F-FDG-PET/CT into
clinical practice for pediatric sarcomas. Although there is a clear role for 18F
FDG-PET/CT in staging pediatric sarcoma, the value of 18F-FDG-PET/CT in
prognostication for pediatric sarcomas remains unclear. In osteosarcoma, Ewing
sarcoma, and rhabdomyosarcoma, 18F-FDG-PET/CT may be most useful in the
identification of skeletal metastases, where the literature consistently suggests
that it has improved sensitivity and specificity as compared to bone
scintigraphy. The role of the imaging modality in the identification of pulmonary
metastatic disease is less clear. Further controversy exists regarding the use of
18F-FDG-PET/CT in predicting outcome. Several studies, particularly in
osteosarcoma, suggest changes in the maximal standardized uptake value (SUVmax)
that can predict histologic response following neoadjuvant chemotherapy as well
as overall outcome. Conversely, studies are conflicting regarding the use of 18F
FDG-PET/CT as a prognostic tool in Ewing sarcoma and rhabdomyosarcoma. The role
of 18F-FDG-PET/CT in pediatric nonrhabdomyosarcoma soft tissue sarcomas is
unknown at this time. Although most studies have been small and retrospective, in
certain histologic subtypes, there is a clear role for the use of this imaging
modality. Additional prospective and larger studies are needed to fully determine
how best to incorporate 18F-FDG-PET/CT into treatment regimens for pediatric
sarcomas in the future.
PMID- 28417854
TI - Current Role of FDG-PET in Pediatric Hodgkin's Lymphoma.
AB - Hodgkin's lymphoma is one of the most curable pediatric cancers with long-term
survival rates exceeding 90% following intensive treatment. Collaborative group
studies worldwide aim on reduction or elimination of radiotherapy to avoid
potentially life-limiting late effects especially second cancers and
cardiovascular diseases. Large prospective trials have integrated early response
FDG-PET scans to identify adequate responders to chemotherapy in whom
radiotherapy may safely be omitted. The criteria for interpretation of early
response PET have changed during the past years and will be further refined based
on trial results. FDG-PET is also systematically used to assess initial disease
involvement of pediatric Hodgkin's lymphoma and could replace bone marrow biopsy.
This article summarizes the role of FDG-PET in staging and response assessment
focusing on large pediatric trials, the criteria for PET interpretation and
pitfalls.
PMID- 28417855
TI - Optimization of Pediatric PET/CT.
AB - PET/CT, the most common form of hybrid imaging, has transformed oncologic imaging
and is increasingly being used for nononcologic applications as well. Performing
PET/CT in children poses unique challenges. Not only are children more sensitive
to the effects of radiation than adults but, following radiation exposure,
children have a longer postexposure life expectancy in which to exhibit adverse
radiation effects. Both the PET and CT components of the study contribute to the
total patient radiation dose, which is one of the most important risks of the
study in this population. Another risk in children, not typically encountered in
adults, is potential neurotoxicity related to the frequent need for general
anesthesia in this patient population. Optimizing pediatric PET/CT requires
making improvements to both the PET and the CT components of the procedure while
decreasing the potential for risk. This can be accomplished through judicious
performance of imaging, the use of recommended pediatric 18fluorine-2-fluoro-2
deoxy-d-glucose (18F-FDG) administered activities, thoughtful selection of
pediatric-specific CT imaging parameters, careful patient preparation, and use of
appropriate patient immobilization. In this article, we will review a variety of
strategies for radiation dose optimization in pediatric 18F-FDG-PET/CT focusing
on these processes. Awareness of and careful selection of pediatric-specific CT
imaging parameters designed for appropriate diagnostic, localization, or
attenuation correction only CT, in conjunction with the use of recommended
radiotracer administered activities, will help to ensure image quality while
limiting patient radiation exposure. Patient preparation, an important
determinant of image quality, is another focus of this review. Appropriate
preparative measures are even more crucial in children in whom there is a higher
incidence of brown fat, which can interfere with study interpretation. Finally,
we will discuss measures to improve the patient experience, the resource use, the
departmental workflow, and the diagnostic performance of the study through the
use of appropriate technology, all in the context of minimizing procedure-related
risks.
PMID- 28417856
TI - Scintigraphic Evaluation of Gastroesophageal Reflux and Pulmonary Aspiration in
Children.
AB - Gastroesophageal reflux (GER) and pulmonary aspiration are encountered in
children of all ages. Signs, symptoms, and complications vary from mild and
transient to severe life-threatening conditions. This review will present
relevant clinical information on these conditions as well as common diagnostic
procedures. The role of scintigraphic techniques used in the evaluation of these
conditions will be discussed in detail including protocols and performance in
comparison to other diagnostic methods.
PMID- 28417857
TI - Nuclear Medicine Imaging in Pediatric Infection or Chronic Inflammatory Diseases.
AB - In this review article, we focus on the most recent applications of nuclear
medicine techniques (mainly 99mTc/111In white blood cells (WBC) scan, [18F]-FDG
PET/CT, [18F]-FDG-PET/MRI, and 99mTc-IL-2 scintigraphy) in the study of children
affected by peripheral bone osteomyelitis, fungal infections, inflammatory bowel
diseases, and type 1 diabetes, owing to recent important published evidences of
their role in the management of these diseases. For osteomyelitis in children,
both bone scintigraphy and [18F]-FDG-PET have a major advantage of assessing the
whole body in one imaging session to confirm or exclude multifocal involvement,
whereas WBC scan has a limited role. In children with fungal infections, [18F]
FDG-PET can help in defining the best location for biopsy and can help in
evaluating the extent of the infection and organs involved (also sites that were
not yet clinically apparent), although its main role is for therapy monitoring.
In inflammatory bowel diseases, and Crohn disease in particular, WBC scan has
been successfully used for many years, but it is now used only in case of
doubtful magnetic resonance (MR) or when MR cannot be performed and endoscopy is
inconclusive. By contrast, there is an accumulating evidence of the role of [18F]
FDG-PET in management of children with Crohn disease, and PET/MR could be a
versatile and innovative hybrid imaging technique that combines the metabolic
information of PET with the high soft tissue resolution of MR, particularly for
distinguishing fibrotic from active strictures. Finally, there are several new
radiopharmaceuticals that specifically target inflammatory cells involved in the
pathogenesis of insulitis aiming at developing new specific immunotherapies and
to select children candidates to these treatments for improving their quality of
life.
PMID- 28417858
TI - 18F-FDG-PET/CT Imaging of Thoracic and Extrathoracic Tuberculosis in Children.
AB - Tuberculosis (TB) remains a major health problem, affecting approximately one
third of the world's population. The tubercle bacillus can affect virtually any
organ of the human body and if left untreated can lead to severe morbidity and
death. Diagnosis of active TB is challenging, especially in children. As a "great
imitator," the disease can mimic numerous other pathologies, both clinically and
at imaging. Although recognition of active TB is crucial to initiate adequate
treatment in a timely fashion, thereby preventing transmission of disease,
differentiation of active and quiescent disease is not always straightforward.
Since the first reports more than 20 years ago, FDG-PET/CT imaging has been shown
to detect active disease with accuracy equal or superior to other conventional
imaging modalities. The role of FDG-PET in evaluating patients with TB is rapidly
expanding. FDG-PET/CT can effectively identify foci of intrathoracic and
extrathoracic TB, assess disease activity, differentiate between active and
latent disease, monitor response to therapy, identify potential biopsy targets,
and serve as a surrogate end point for new drug trials. Efficacy of FDG-PET/CT in
the especially challenging pediatric population will be the focus of this review.
PMID- 28417859
TI - Cardiovascular Surgery in the Elderly.
AB - The elderly population is the fastest growing demographic in Western countries.
As the population ages, the incidence of age-related comorbidities such as
diabetes mellitus, chronic obstructive pulmonary disease, peripheral vascular
disease, renal disease, cerebrovascular disease, and cardiovascular disease
increases. With cardiovascular disease occurring in approximately one-quarter of
the population over the age of 75 years and more than half of all cardiac
procedures performed on this age group, the number of potential elderly surgical
candidates is increasing. However, data suggest that old age is associated with
increased morbidity and mortality following cardiac surgery. Over the past 2
decades, improvements in myocardial protection, extracorporeal circulation,
anesthesia, and surgical techniques have significantly reduced the morbidity and
mortality associated with cardiac surgery. Although most prospective studies
exclude elderly patients, data from large retrospective studies and subgroup
analyses suggest that cardiac surgery is a viable option for many elderly
patients with cardiovascular disease, with good outcomes observed in reasonable
risk candidates; moreover, there are a growing number of available less-invasive
options for them when surgical risk becomes prohibitive. In this article, we
discuss the current state of cardiovascular surgery in the elderly as well as
emerging technologies on the horizon.
PMID- 28417860
TI - Similar Survival After Repair vs Replacement for Ischemic Mitral Regurgitation.
AB - To determine whether mitral valve (MV) repair improves early and late survival
compared with MV replacement for patients with ischemic mitral regurgitation
(IMR), we performed a meta-analysis of randomized controlled trials (RCTs) and
adjusted observational studies. Databases including MEDLINE, EMBASE, and the
Cochrane Central Register of Controlled Trials were searched through January 2016
using PubMed and Ovid. Studies considered for inclusion met the following
criteria: the design was a RCT or adjusted observational study, the study
population was patients with IMR; patients were assigned to MV repair vs
replacement, and outcomes included early (30 days or in hospital) or late (>=1
year) overall survival or all-cause mortality. An adjusted odds or hazard ratio
(OR/HR) with its 95% CI of early or late (including early) all-cause mortality
for MV repair vs replacement was abstracted from each individual study. Our
search identified 12 articles from one RCT and 10 adjusted observational studies
including 2784 patients. Pooled analyses demonstrated no significant difference
in both early (OR = 0.90; 95% CI: 0.69-1.16; P = 0.41) and late mortality (HR =
0.90; 95% CI: 0.72-1.13; P = 0.38) between MV repair and replacement. Exclusion
of any single study from the meta-analysis did not substantively alter the
overall result of no significant difference. There was no evidence of significant
publication bias. For patients with IMR, MV repair appears to be unassociated
with a significant decrease in both early and late all-cause mortality compared
with MV replacement.
PMID- 28417862
TI - Angel in the Architecture and the Devil in the Details: Comparative
Ultrastructure of Degenerative Mitral Valve Disease.
PMID- 28417861
TI - Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and
Fibroelastic Deficiency.
AB - Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of
mitral valve prolapse (MVP), should be considered 2 distinct diseases remains
unknown. Mitral valves from patients who required surgery for severe mitral
regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative
diagnosis of BD or FED was based on leaflet redundancy and thickness, number of
segments involved, and annular dimension. The removed medial scallop of the
posterior leaflet and attached chordae were used for histopathological and
immunohistological assessment. Histologically, compared to normal controls (n =
3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture
and increased thickness. Leaflet thickness was greater and chordae thickness
lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to
spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa
and atrialis; in FED, local thickening was predominant on the fibrosa side, with
accumulation of proteoglycan-like material around the chordae. Collagen
accumulation was observed in FED leaflets and chords and decreased in BD.
Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but
increased in FED leaflets and around chordae. Activated myofibroblasts accumulate
in both diseased leaflets and chords, but more abundantly in FED chordae (P <
0.0001), independently of age, suggesting a role of these cells in chordal
rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P
< 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were
more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P
< 0.01) indicating tissue remodeling. Upregulation of transforming growth factor
beta and pERK signaling pathways was evident in both diseases but more prominent
in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in
FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in
control valves. Quantitative immunohistopathological analyses demonstrated
distinct changes between BD and FED valves: predominant matrix degradation in BD
and increased profibrotic signaling pathways in FED, indicating that BD and FED
are 2 different entities. These results may pave the way for genetic studies of
MVP and development of preventive drug therapies.
PMID- 28417863
TI - Evaluation of a High-Fidelity Simulation Training Program for New Cardiothoracic
Intensive Care Unit Nurses.
AB - The objective of this article is to evaluate the effect of a high-fidelity
simulation training program on knowledge and confidence as part of a nursing
internship in the cardiothoracic intensive care unit. Ten nurse interns each
completed a simulation scenario involving common postoperative complications
followed by a group debriefing session. Knowledge and confidence were assessed
using a multiple-choice test and modified self-efficacy scale, respectively. Both
were administered precourse and postcourse and again 2 weeks later. The
simulation effectiveness tool, a 0-2 scale with higher scores indicating higher
degree of perceived effectiveness, was used to evaluate participants' perceptions
of the program. Paired t-tests compared precourse and postcourse scores as well
as postcourse and follow-up scores for both knowledge and confidence. Spearman
rho compared subjective with objective assessment of learning and improvement in
learning with improvement in confidence. Mean knowledge scores improved from
48.18% (standard deviation [SD] = 14.7) to 60.9% (SD = 22.6; P < 0.05) and
confidence scores improved from 20.8 (SD = 5.17) to 25.9 (SD = 3.3; P < 0.05),
both with insignificant changes 2 weeks later. The simulation effectiveness tool
mean score was 1.64 (SD = 0.56). There was no correlation between the objective
and subjective learning assessments or between the improvement in learning and
improvement in confidence. The inclusion of a high-fidelity simulation course
showed improvement in both learning and confidence among the new graduate nurses;
however, objective assessment of learning is needed. It is also important to note
that an improvement in confidence may not indicate an improvement in actual
ability.
PMID- 28417864
TI - Paradigm for Detecting Silent Thoracic Aneurysm Disease.
AB - Thoracic aortic aneurysms (TAA) pose a serious detection challenge owing to their
clinically silent nature. Only a small fraction of TAAs cause symptoms in
patients. However, the mortality burden of this disease in the population is
significant, given the high lethality of such complications as aortic rupture and
dissection. Widespread screening for TAA has not been shown to be cost-effective.
Therefore, currently most patients with a TAA are identified incidentally during
an imaging study conducted for other reasons. Once a TAA diagnosis is
established, prophylactic surgical treatment can safely be performed for
aneurysms of the ascending aorta, aortic arch, and descending or thoracoabdominal
aorta, thus preventing aneurysm-related death. To facilitate early detection of
TAA, recent studies have identified several "associates" of TAA that may be
useful in making a timely diagnosis. These "associates" include intracranial
aneurysm, aortic arch anomalies, abdominal aortic aneurysm, simple renal cysts,
bicuspid aortic valve, temporal arteritis, a positive family history of aneurysm
disease, and a positive thumb-palm sign, among others. Although for many of these
"associates" the underlying mechanism that would explain the association remains
to be elucidated, the clinical correlation is strong enough to suggest screening
patients with these findings for TAA. This article introduces the "Guilt by
Association" paradigm for detection of silent thoracic aortic disease based on
detection of clinical markers associated with this condition.
PMID- 28417865
TI - Management of Symptomatic Severe Aortic Stenosis in Patient With Very Severe
Chronic Obstructive Pulmonary Disease.
AB - Transcatheter aortic valve replacement (TAVR) is a viable option for patients
with severe chronic obstructive pulmonary disease (COPD) who are deemed
inoperable or high risk for surgery. We sought to determine outcomes of patients
with severe aortic stenosis (AS) and severe COPD referred for aortic valve
replacement (AVR). One hundred thirty-one patients with severe AS and severe COPD
(GOLD criteria) were evaluated at our center between 2008 and 2013 and were
divided retrospectively into 4 groups: 1-medical management, 2-balloon aortic
valvuloplasty, 3-surgical aortic valve replacement (SAVR), and 4-TAVR. Baseline,
clinical, and echo data were recorded. Primary outcome was cardiovascular death.
From the study cohort, 54 (41.2%), 29 (22.1%), 21 (16.0%), and 27 (20.6%) were
included in groups 1-4, respectively; the age was 74.9 +/- 8.8, 76.2 +/- 8.8,
78.8 +/- 7.4, and 82.8 +/- 6.8 years, respectively (P < 0.01). There was no
significant difference between the groups for hypertension, diabetes, aortic
valve area or gradients, forced expiratory volume in first second, right
ventricular systolic pressure, ejection fraction, and Society of Thoracic
Surgeons predicted risk of mortality score. At 3 +/- 1.5 years, death occurred in
87%, 97%, 47.7%, and 51.8% of patients in groups 1-4, respectively. Heart failure
readmissions occurred in 43%, 42%, 9.6%, and 14.8% of patients in groups 1-4,
respectively. When SAVR and TAVR groups were compared, there was no significant
difference in survival (P = 0.719) or heart failure readmissions (P = 0.19). In
patients with severe or very severe COPD and severe AS, replacing the severely
stenotic aortic valve by either SAVR or TAVR improves survival and reduces
rehospitalization compared with medical therapy or balloon aortic valvuloplasty.
PMID- 28417866
TI - Anomalous Aortic Origin of Coronary Arteries: A Single-Center Experience.
AB - The aim of this article is to determine the clinical course and outcomes in
subjects with anomalous aortic origin of coronary arteries (AAOCA), particularly
after surgical repair. A single-center, retrospective review of patients with
AAOCA with right or left interarterial or IM (IA or IM) or intraconal course from
1996-2014. Among 155 patients, median age at diagnosis was 8.5 (range: 0.1-50)
years, and 65% were male. The AAOCA course was IA or IM in 151 (97%) and
intraconal in 4 (3%). Anomalous right coronary artery (CA) was present in 127
(82%), of whom 52 (42%) had repair. Anomalous left CA (ALCA) was present in 28
(18%), of whom 20 (71%) had repair. In the surgical group, 70 (97%) had IA or IM
CAs; CA unroofing was performed in 62 (86%). In univariable analysis, surgical
management was associated with ALCA (28% vs 10%, P = 0.003), age > 10 years
(median 11 vs 6 years, P < 0.001), symptoms (63% vs 13%, P < 0.001), and exercise
restriction at the time of diagnosis (47% vs 13%, P < 0.001). In multivariable
modeling, surgery was associated with chest pain or syncope (P < 0.001) and older
age (P = 0.03). Major perioperative complications occurred in 4 cases (6%) and 1
patient had late aortic valve repair. In the surgical group, no patients died; in
the observed group, 2 patients with anomalous right CA (2.3%) died of severe
noncardiac comorbidities. In our center, surgery for AAOCA was not associated
with mortality, and surgery was recommended in patients with ALCA with IA or IM
course. Rare but serious surgical complications highlight the importance of long
term follow up of patients with AAOCA to develop evidence-based management
guidelines.
PMID- 28417867
TI - Wrong Sinus Coronary Arteries: Another Piece of the Puzzle.
PMID- 28417868
TI - Risk Factors for Unanticipated Readmissions During the Interstage: A Report From
the National Pediatric Cardiology Quality Improvement Collaborative.
AB - This study describes unanticipated interstage readmissions in patients with
hypoplastic left heart syndrome, identifies independent risk factors for
unanticipated interstage readmissions, and evaluates variation in unanticipated
readmission rates among collaborative centers. Retrospective data of patients
enrolled in the National Pediatric Cardiology Quality Improvement Collaborative
registry from July 2008 to July 2013 were analyzed. Risk factors present at the
beginning of the interstage were captured. Competing risks time to event analyses
determined the association between these factors and unanticipated interstage
readmission. Readmission center variation was examined using funnel plots.
Unanticipated interstage readmissions occurred in 66% of 815 patients at 50
centers. The median readmission length of stay was 2 days (interquartile range: 0
6) and median time to first readmission was 29 days (interquartile range: 9-63).
Most readmissions were prompted by minor changes in clinical status (64%),
whereas only 6% were major adverse event readmissions. Independent readmission
risk factors included genetic syndrome (HR = 1.40, 95% CI: 1.05-1.88), center
volume (small vs large HR = 1.32, CI: 1.04-1.66, medium vs large HR = 1.35, CI:
1.09-1.68), preoperative ventricular dysfunction (HR = 2.02, CI: 1.31-3.10),
tricuspid regurgitation (HR = 1.36, CI: 1.08-1.72), duration of circulatory
arrest (HR = 0.99, CI: 0.989-0.998), and undergoing Hybrid procedure relative to
Norwood/right ventricle to pulmonary artery conduit (HR = 1.40, CI: 1.02-1.93).
There was significant center variation in the number of readmissions and duration
of readmissions. Unanticipated readmissions are common during the interstage
period with notable center variation. However, these readmissions are short and
are rarely in response to major adverse events.
PMID- 28417869
TI - Unanticipated Readmissions During the Interstage Period in Patients With
Hypoplastic Left Heart Syndrome: Can the Numbers be Safely Reduced?
PMID- 28417870
TI - Intracoronary Stem Cell Delivery to the Right Ventricle: A Preclinical Study.
AB - Clinical protocols for stem cell-based therapies are currently under development
for patients with hypoplastic left heart syndrome. An ideal cell delivery method
should have minimal safety risks and provide a wide distribution of cells to the
nonischemic right ventricle (RV). However, the optimal strategy for stem cell
delivery to the RV has yet to be explored in a preclinical model, necessary for a
hypoplastic left heart syndrome trial. Human c-kit+ cardiac stem cells (CSCs)
were delivered to healthy Yorkshire swine through the proximal right coronary
artery with a stop and reflow technique. The effect of premedication with
antiarrhythmic (AA) medications in this model was retrospectively reviewed, with
the primary outcome of survival 2 hours after infusion. A group underwent CSC
delivery to the RV without prophylactic AA medication (no AA, n = 7), whereas the
second group was premedicated with a loading dose and intravenous infusion of
amiodarone and lidocaine (AA, n = 13). Cardiac biopsies were obtained from each
chamber to ascertain the biodistribution of CSCs. Survival was significantly
greater in the prophylactic AA group compared with the group without AA (13/13
[100%] vs 1/7 [14.3%], P < 0.0001). Cardiac arrest during balloon inflation was
the cause of death in each of the nonmedicated animals. In the premedicated
group, 9 (69.2%) pigs experienced transient ST segment changes in the precordial
leads during CSC delivery, which resolved spontaneously. Most c-kit+ CSCs were
distributed to lateral segments of the RV free wall, consistent with the
anatomical course of the right coronary artery (lateral RV, 19.2 +/- 1.5
CSCs/field of view vs medial RV, 10.4 +/- 1.3 CSCs/field of view, P < 0.0001).
Few c-kit+ CSCs were identified in the right atrium, septum, or left ventricle.
Prophylactic infusion of AA enhances survival in swine undergoing intracoronary
delivery of human c-kit+ CSCs to the RV. Additionally, intracoronary delivery
results in a limited biodistribution of c-kit+ CSCs within the RV. Human clinical
protocols can be optimized by requiring infusion of AA medications before cell
delivery.
PMID- 28417871
TI - A Light in the Darkness: Lighthouse or Anglerfish?
PMID- 28417872
TI - Brown adipose tissue and browning: More than just a heating device.
PMID- 28417873
TI - Trends in the incidence of lower limb amputation after implementation of a
Multidisciplinary Diabetic Foot Unit.
AB - BACKGROUNDS AND OBJECTIVE: Incidence of lower extremity amputations (LEA) in the
population with and without diabetes mellitus (DM) was assessed after
implementation of a Multidisciplinary Diabetic Foot Unit (MDFU) during 2008.
MATERIAL AND METHODS: Non-traumatic LEA were analyzed, and those performed before
(2001-2007) and after (2008-2014) introduction of the MDFU were compared. LEA
were grouped by age and sex. Their incidence was expressed as a rate per 100,000
population per year, adjusted to the standard European population. RESULTS: A
total of 664 LEA were performed during the 2001-2014 period, 486 (73%) of them in
patients with DM. Total LEA incidence was 11.2/105 population in DM versus
3.9/105 in the population without DM. Incidence of major LEA in patients with DM
significantly decreased from 6.1/105 population in the 2001-2007 period to
4.5/105 in the 2008-2014 period (p=.03). Joinpoint regression analysis also
showed a reduction in the trend of incidence of major LEA in patients with DM,
with an annual percentage change of -3.3% [95% CI, -6.2-0.3] (p=.025). No
significant differences were found for all other incidences and trends in the
diabetic and non-diabetic populations. CONCLUSIONS: Implementation of a MDFU has
been shown to be associated with a significant reduction in major amputation rate
in the diabetic population, although the results are not optimal yet. Both
results and work at the MDFU should be improved.
PMID- 28417874
TI - Effectiveness of MiniMed 640G with SmartGuard(r) System for prevention of
hypoglycemia in pediatric patients with type 1 diabetes mellitus.
AB - INTRODUCTION/AIMS: Treatment with the MiniMed 640G-SmartGuard(r) system (640G-SG,
sensor-augmented insulin pump system with low predicted glucose suspension
feature) has been shown to decrease risk of hypoglycemia without altering
metabolic control in patients with T1DM. The study purpose was to assess the
impact of 640G-SG on hipoglycemia frequency and on metabolic control in a
pediatric population with T1DM. PATIENTS/METHODS: A retrospective study on 21
children treated with 640G-SG. HbA1C, mean blood glucose (mg/dl), glucose
variation coefficient, frequency of hypoglycemia (<70mg/dl) and hyperglycemia
(>180mg/dl), daily capillary blood glucose measurements, ketosis/diabetic
ketoacidosis, and severe hypoglycemic episodes were analyzed and compared before
and during use of the system. Fasting blood glucose, frequency of sensor use and
number and duration of system suspension events were also assessed in the last
month of use of the system. RESULTS: All patients used the system continuously
(5.0+/-2.1 months), with a median sensor use of 92%. Significant decreases were
seen in hypoglycemia frequency (10.4+/-5.2% to 7.6+/-3.3%, p=.044) and number of
capillary blood glucose measurements (11.3+/-2,2 to 8.1+/-2,1, p<.001), and there
was no increase in hyperglycemia frequency (p=.65). Mean system suspension time
was 3.1+/-1.2hours/day (37.3% of overnight stops). Changes in HbA1c, mean blood
glucose, and variation coefficient were not significant. No patient experienced
diabetic ketoacidosis or severe hypoglycemia. CONCLUSIONS: The sensor-augmented
pump with the predictive low glucose suspension management system, as implemented
in the 640G-SG system, can help avoid risk of hypoglycemia without significantly
affecting metabolic control or causing diabetic ketoacidosis, and decrease the
burden of additional capillary blood glucose measurements in our pediatric
cohort.
PMID- 28417875
TI - Influence of malnutrition upon all-cause mortality among children in Swaziland.
AB - OBJECTIVE: To analyze the effect of the type of malnutrition, sex, age and the
presence of edema upon all-cause mortality in children under 5 years of age.
MATERIAL AND METHODS: A cross-sectional study was conducted during 2010 and 2011
in Swaziland. Sex, age, weight and height were taken to classify nutritional
status according to the 2006 WHO growth standards: stunting (low height for age),
wasting (low weight for height or low body mass index for age) and underweight
(low weight for age). The sample (309 boys and 244 girls under 5 years of age)
was analyzed by sex and age groups (under and equal/over 12 months). The
association between variables was evaluated using the chi2 test. Cox regression
analysis (HR, 95% CI) was used to assess the likelihood of mortality. RESULTS:
The mortality risk in malnourished children under one year of age was lower among
females and increased in the presence of severe edema. Wasting combined with
underweight increased the mortality risk in children under 12 months of age 5
fold, versus 11-fold in older children. The combination of stunting, wasting and
underweight was closely associated to mortality. Stunting alone (not combined
with wasting) did not significantly increase the mortality risk. CONCLUSIONS:
Sex, severe edema and wasting are predictors of mortality in malnourished
children. Regardless of these factors, children with deficiencies referred to
weight for height and weight for age present a greater mortality risk in
comparison with children who present stunting only.
PMID- 28417876
TI - Insulin resistance and beta-cell function in Colombian mestizo and Embera-Chami
populations and their relation with adiposity degree.
AB - BACKGROUND AND OBJECTIVE: Insulin resistance (IR) is a condition favored by
metabolic and endocrine changes experienced by adipose tissue in the context of
obesity. The prevalence and the presentation of both IR and obesity vary among
the populations, and may be affected by ancestral genetic composition among other
factors. The aim of this study was to compare the presence of IR and obesity in
Amerindians of the Embera-Chami ethnicity and Colombian mestizo population.
PATIENTS AND METHODS: A sample of 630 individuals, 471 mestizos and 159
Amerindians of the Embera-Chami ethnicity, from the general population of
Colombia were studied. For each participant, anthropometric and biochemical
measurements, as well as blood pressure and the Homeostatic Model Assessment
(HOMA) of IR and beta-cell function (%B) were recorded. These values were
compared between the two populations. RESULTS: While prevalence of central
obesity was similar in both populations (48.7% and 42.6% in the mestizo and
Embera groups respectively; p=0.148), body mass index (BMI) values suggested a
higher prevalence of overweight in the Embera than in mestizo population (43.4%
Embera, 31.8% mestizo; p=0.027). Despite the similarities in the prevalence of
HOMA-IR and HOMA-%B status between both populations, the Embera population had a
significantly greater pancreatic beta-cell function, higher insulin levels, and
better glucose control, across BMI and central obesity categories, than the
mestizo population. CONCLUSION: There are differences in aspects related to
energy metabolism between the samples of the mestizo and Amerindian populations
analyzed.
PMID- 28417877
TI - Tobacco and diabetes: clinical relevance and approach to smoking cessation in
diabetic smokers.
AB - Smoking is, together with diabetes mellitus, one of the main risk factors for
cardiovascular disease. Diabetic patients have unique features and
characteristics, some of which are not well known, that cause smoking to
aggravate the effects of diabetes and impose difficulties in the smoking
cessation process, for which a specificand more intensive approach with stricter
controls is required. This review details all aspects with a known influence on
the interaction between smoking and diabetes, both as regards the increased risk
of macrovascular and microvascular complications of diabetes and the factors with
an impact on the results of smoking cessation programs. The treatment guidelines
for these smokers, including the algorithms and drug treatment patterns which
have proved most useful based on scientific evidence, are also discussed.
PMID- 28417879
TI - Comments on "Carcinoma de tiroides incidental versus no incidental: presentacion
clinica, tratamiento quirurgico y pronostico".
PMID- 28417878
TI - Comments on "Incidental versus non-incidental thyroid carcinoma: Clinical
presentation, surgical management and prognosis".
PMID- 28417880
TI - The Japan Prosthodontic Society is establishing the Journal of Prosthodontic
Research (JPR) Best Paper Award.
PMID- 28417881
TI - Understanding GPCR signaling in the brain- the path to CNS drug discovery.
PMID- 28417883
TI - From the Editor's desk...: May 2017.
PMID- 28417884
TI - Farewell from the EASL Secretary General.
PMID- 28417882
TI - EASL Clinical Practical Guidelines on the management of acute (fulminant) liver
failure.
AB - The term acute liver failure (ALF) is frequently applied as a generic expression
to describe patients presenting with or developing an acute episode of liver
dysfunction. In the context of hepatological practice, however, ALF refers to a
highly specific and rare syndrome, characterised by an acute abnormality of liver
blood tests in an individual without underlying chronic liver disease. The
disease process is associated with development of a coagulopathy of liver
aetiology, and clinically apparent altered level of consciousness due to hepatic
encephalopathy. Several important measures are immediately necessary when the
patient presents for medical attention. These, as well as additional clinical
procedures will be the subject of these clinical practice guidelines.
PMID- 28417885
TI - EASL Recognition Award Recipient 2017: Prof. Gustav Paumgartner.
PMID- 28417886
TI - EASL Recognition Award Recipient 2017: Prof. Giorgina Mieli-Vergani.
PMID- 28417887
TI - EASL International Recognition Award Recipient 2017: Professor Kenjiro Wake.
PMID- 28417888
TI - General Concepts of Patient Safety for the Oral and Maxillofacial Surgeon.
AB - Whether managing patients in private offices or as part of a care team at
hospitals, oral and maxillofacial surgeons owe it to patients to understand
medical error and take action to reduce its frequency and adverse effects. This
article reviews general concepts of patient safety, including high-reliability
organization, crew resource management, simulation training, root cause analysis,
and just culture.
PMID- 28417889
TI - Monitoring for the Oral and Maxillofacial Surgeon.
AB - Parenteral medications are titrated in the oral and maxillofacial surgery office
to achieve moderate sedation, deep sedation, or general anesthesia while
continuously maintaining spontaneous ventilation with an open airway. After
initial drug administration, the provider assesses and interprets both the level
of anesthesia and the presence/severity of adverse side effects, both of which
guide further drug titration, cessation, reversal, or medical management. This
assessment is called monitoring, which guides the conduct of anesthesia delivery
and becomes the essence of this art.
PMID- 28417890
TI - Fire Safety for the Oral and Maxillofacial Surgeon and Surgical Staff.
AB - Fire in the operating room is a life-threatening emergency that demands quick,
efficient intervention. Because the circumstances surrounding fires are generally
well-understood, virtually every operating room fire is preventable. Before every
operating room case, thorough preprocedure "time outs" should address each team
members' awareness of specific fire risks and agreement regarding fire concerns
and emergency actions. Fire prevention centers on 3 constituent parts of the fire
triad necessary for fire formation. Regular fire drills should guide policies and
procedures to prevent surgical fires. Delivering optimal patient care in emergent
situations requires surgical team training, practicing emergency roles, and
specific actions.
PMID- 28417891
TI - Outpatient Anesthetic Safety Considerations for Obstructive Sleep Apnea.
AB - Most patients with obstructive sleep apnea (OSA) are not diagnosed
preoperatively. The STOP-Bang questionnaire may identify patients at risk of OSA,
especially those with severe OSA. Patients with mild to moderate OSA, with
optimized comorbidities, can usually safely undergo outpatient surgery. Patients
with severe OSA, who are not optimized medically, should avoid outpatient
surgery.
PMID- 28417892
TI - Discharge Criteria, Impact of the Patient and the Procedure: What the Oral
Surgeon Should Know.
AB - This article is a concise review of discharge criteria following sedation or
anesthesia relevant to the oral and maxillofacial surgeon. Topics covered include
a general overview of the need for objective discharge criteria, a review of
standardized criteria, and a brief discussion on specific anesthetic, patient,
and surgical factors that can impact the safety of the immediate postoperative
recovery and postdischarge periods.
PMID- 28417893
TI - Equipment Safety, Maintenance and Inspection: What the Oral Surgeon Needs to
Know.
AB - Many oral and maxillofacial surgical procedures are done in an office-based
setting, with many oral and maxillofacial surgeons involved in oversight of
equipment maintenance. Goals in equipment management are to prevent harm to
patients and staff, stay compliant with current regulations, and increase
equipment longevity. This article covers the safety, maintenance, and inspection
related to electrical equipment used in the treatment of patients, autoclaves,
radiograph machines, nitrous oxide and oxygen medical gases, and required back-up
power and lighting. An office should always follow manufacturer's recommendations
regarding maintenance and inspection and document policies and monitoring so
compliance can be assured.
PMID- 28417894
TI - Quality Improvement and Reporting Systems: What the Oral and Maxillofacial
Surgeon Should Know.
AB - Health care is an inherently dangerous environment, and patient safety should be
an explicit goal of oral and maxillofacial surgery. Important components of a
safety program include a nonpunitive safety culture, the implementation of
patient safety practices, standardized incident reporting and adverse event
analysis, regular self-assessment, and internal and external benchmarking.
Implementation of a safety program requires the strong commitment of leadership
and the engagement and empowerment of all employees. Oral and maxillofacial
surgery can become the model dental specialty by implementing patient safety
programs for office-based surgery. The programs could then be used by all dental
practitioners performing oral surgery in the office.
PMID- 28417895
TI - Preface.
PMID- 28417896
TI - Production and Precipitation Hardening of Mg-Ca-Zn-Co Alloy for Tissue
Engineering.
AB - In this study, Mg-Ca-Zn-Co alloy specimens for biomedical applications were
produced by the powder metallurgy method. The Mg-Ca-Zn-Co alloy could be used as
a scaffold material in tissue engineering applications. Electrochemical corrosion
behavior of the specimens was investigated in simulated body fluid environment.
Electrochemical corrosion resistance of the specimens was increased with
increasing Zn and Ca contents of the alloy up to an optimum composition and then
decreased. Optimum values for Ca and Zn additions were about 0.7 wt.% and 3.0
wt.% respectively. Young's modulus values of the specimens were determined by
nondestructive ultrasonic measurement. Alloying element addition increased the
Young's modulus of the specimens. Precipitation hardening of the Mg-Ca-Zn-Co
alloy increased the Young's modulus and the corrosion rate of the specimens.
PMID- 28417897
TI - Oral magnesium supplementation reduces the incidence of gastrointestinal
complications following cardiac surgery: a randomized clinical trial.
AB - Gastrointestinal complications are common after coronary artery bypass graft
surgery. These complications are ranged from nausea and vomiting to mesenteric
ischemia and liver failure. It seems that nausea, vomiting, and constipation are
related to magnesium deficiency. This study was designed to examine the effect of
oral magnesium supplementation on the incidence of gastrointestinal complications
in patients undergoing cardiac surgery. In a single blinded randomized clinical
trial, 102 patients who were undergoing coronary artery bypass graft surgery were
randomly allocated into two groups, 52 patients in the intervention and 50
patients in control group. Patients in the experimental group received 800
milligram magnesium oxide (2 tablets each of them containing 240 mg elemental
magnesium) daily from the admission to discharge from hospital. The incidence of
post-operative nausea and vomiting, constipation, and atrial fibrillation was
compared between the groups. Our results showed that postoperative hypomagnesemia
is present in 41.20 and 70.80 percent of the patients in the intervention and
control group patients, respectively. The overall incidence of constipation was
62%. Patients who received magnesium supplementation experienced less atrial
fibrillation, nausea, vomiting, and constipation. Our data showed that oral
magnesium supplementation could reduce the postoperative complications. Despite
the better status in the intervention group, the hypomagnesemia was present in
many of intervention group patients. It seems that supplementation with higher
doses is needed.
PMID- 28417898
TI - Nanoscale influence on photoluminescence and third order nonlinear susceptibility
exhibited by ion-implanted Pt nanoparticles in silica.
AB - A systematic study has been carried out to investigate photoluminescence and
third order nonlinear ultraviolet properties exhibited by platinum nanoparticles
nucleated in a high-purity silica matrix. The modification in the characteristic
photoluminescence spectra of the nanocomposites, ranging between 400 and 600 nm,
was obtained with the assistance of a thermal annealing process that changed the
average size of the platinum nanoparticles. The influence of temperature, between
200 degrees C-1100 degrees C, during the thermal treatment of the
nanostructures was analyzed. UV-vis spectroscopy studies corroborated changes in
the optical absorption resonances of the ion-implanted samples after annealing,
which could then be correlated with the average size of the nanoparticles. The
estimated average size was also corroborated by transmision electron microscopy.
For temperatures below 600 degrees C the system is mainly composed of ultra
small photoluminescent platinum nanoparticles. Larger platinum nanoparticles were
formed at higher annealing temperatures but photoluminescence quenching was
observed as the typical plasmonics response of larger metal nanoparticles started
to emerge. The photoluminescence emission for samples with a particle size of
less than 2 nm is enhanced approximately 12 fold with respect to the samples with
a particle size in the range of 3-7 nm. Differences in the resulting
photoluminescence spectra were revealed by substituting the participation of
argon, hydrogen or nitrogen, as environmental gases for thermal annealing. A weak
PL emission, featuring 1.5 nW at a laser excitation power of 800 MUW, related to
larger platinum nanoparticles was observed. New emission peaks emerging from the
larger platinum nanoparticles were associated with possible hydrogen adsorption
on the nanoparticles' surface. Third order nonlinear ultraviolet measurements
were conducted using a time-resolved two-wave mixing method with self-diffraction
at 355 nm wavelength. The observed self-diffraction decay time is less than 25
ps, regardless of the average size of the nanoparticles studied. The evolution of
the self-diffracted intensities derived from temperature was also linked to the
mean size of the nanoparticles in the samples. Comparative two-wave mixing
evaluations also validated a modification in third order nonlinear susceptibility
exhibited by annealed samples. An important role of the localized surface plasmon
resonance phenomena associated with the platinum nanoparticles for
photoluminescence and optical nonlinearities was identified. A proposed
hypothetical electronic mechanism that may explain the exceptional optical
transitions related to low-dimensional platinum systems is discussed.
PMID- 28417899
TI - Synergistic interaction between pseudocapacitive Fe3O4 nanoparticles and highly
porous silicon carbide for high-performance electrodes as electrochemical
supercapacitors.
AB - Composites of micro- and mesoporous SiC flakes (SiCF) and ferroferric oxide
(Fe3O4), SiCF/Fe3O4, were prepared via the chemical deposition of Fe3O4 on SiCF
by the chemical reduction of an Fe precursor. The SiCF/Fe3O4 electrodes were
fabricated at different Fe3O4 feeding ratios to determine the optimal Fe3O4
content that can maintain a high total surface area of SiCF/Fe3O4 composites as
well as cause a vigorous redox reaction, thereby maximizing the synergistic
effect between the electric double-layer capacitive effects of SiCF and the
pseudo-capacitive effects of Fe3O4. The SiCF/Fe3O4 electrode fabricated with a
Fe3O4/SiCF feeding ratio of 1.5:1 (SiCF/Fe3O4(1.5)) exhibited the highest charge
storage capacity, showing a specific capacitance of 423.2 F g-1 at a scan rate of
5 mV s-1 with a rate performance of 81.8% from 5 to 500 mV s-1 in an aqueous 1 M
KOH electrolyte. The outstanding capacitive performance of the SiCF/Fe3O4(1.5)
electrode could be attributed to the harmonious synergistic effect between the
electric double-layer capacitive contribution of the SiCF and the
pseudocapacitive contribution of the Fe3O4 nanoparticles introduced on the SiCF
surface. These encouraging results demonstrate that the SiCF/Fe3O4(1.5) electrode
is a promising high-performance electrode material for use in supercapacitors.
PMID- 28417900
TI - Green approach to photoluminescent carbon dots for imaging of gram-negative
bacteria Escherichia coli.
AB - Fluorescent carbon dots, zero-dimensional nanomaterials with surface ligands,
have been studied extensively over the past few years in biolabelling or
fluorescence-based live cell assays. In the past, synthetic organic dyes have
been used as cell tracking materials, but they have severe limitations;
fluorescent carbon dots may pave the way to biolabelling and cell imaging. In
this work, green fluorescent carbon dots have been synthesized from a green
source, gram, without any sort of covalent or ionic modifications. These gram
derived carbon dots are unique with respect to synthetic commercial cell-tracking
dyes as they are non-toxic, cell internalization occurs quickly, and they have
excellent bioconjugation with bacterial cells. Our aim is to establish these
carbon dots in a biolabelling assay with its other physicochemical features like
the tunable luminescence property, high degree of water solubility and low
toxicity, towards various environments (wide range of pH, high ionic strength).
Our study introduces a new perspective on the commercialization of carbon dots as
a potential alternative to synthetic organic dyes for fluorescence-based cell
labelling assays.
PMID- 28417901
TI - Tunable bending stiffness of MoSe2/WSe2 heterobilayers from flexural wrinkling.
AB - Understanding the mechanical behaviors of van der Waals heterogeneous 2D
materials is important for their actual applications. Our extensive first
principles calculations and continuum mechanical modeling on the wrinkling of
MoSe2/WSe2 heterobilayers caused by compression reveal that the bending stiffness
of MoSe2/WSe2 wrinkles strongly depend on the wrinkle structures, which first
increase and then decrease with increasing the compressive strain. The bending
stiffness of MoSe2/WSe2 wrinkles could be effectively mediated and tuned by
adjusting the wrinkle geometry and size. The underlying mechanisms are elucidated
by the differences in electronic structures and bonding states at the top, middle
and bottom parts of the wrinkles, and the relevance of the changes of bond
lengths to flexural deformation. Our results suggest a feasible way to develop
flexible devices and nanoelectromechanical systems by utilizing the correlation
and coupling between the mechanical and electronic properties in MoSe2/WSe2
wrinkles.
PMID- 28417902
TI - A NIR fluorescent probe for the rapid detection of Hg2+ in living cells and in
vivo mice imaging.
AB - A near-infrared fluorescent probe NIR-Hg, for the detection of Hg2+ ion, has been
synthesized directly by condensing Changsha dye with 4-Phenyl-3-thiosemicarbazide
and the structure has fully characterized by 1HNMR, 13CNMR, and ESI-MS. The probe
has been designed on the basis of the reaction that Hg2+ ion promotes
thiosemicarbazide to oxazole in aqueous media and had been induced to produce
turn-on fluorescence via an irreversible spirolactam ring-opening process. The
probe NIR-Hg has exhibited fast response (1 min), high sensitivity with 44-fold
fluorescence intensity enhancement under six equivalent amounts of Hg2+ added,
high selectivity over other related metal ions and a low detection limit of 5.8 *
10-8 M in the phosphate buffer. The linear response range covers the
concentration of Hg2+ from 5 * 10-7 to 5 * 10-6 M. In addition, the probe has
good cell-membrane permeability, which is suitable for fluorescence imaging for
Hg2+ in living cells and in vivo mice.
PMID- 28417903
TI - An Assessment of the Potential Use of BNNTs for Boron Neutron Capture Therapy.
AB - Currently, nanostructured compounds have been standing out for their optical,
mechanical, and chemical features and for the possibilities of manipulation and
regulation of complex biological processes. One of these compounds is boron
nitride nanotubes (BNNTs), which are a nanostructured material analog to carbon
nanotubes, but formed of nitrogen and boron atoms. BNNTs present high thermal
stability along with high chemical inertia. Among biological applications, its
biocompatibility, cellular uptake, and functionalization potential can be
highlighted, in addition to its eased utilization due to its nanometric size and
tumor cell internalization. When it comes to new forms of therapy, we can draw
attention to boron neutron capture therapy (BNCT), an experimental radiotherapy
characterized by a boron-10 isotope carrier inside the target and a thermal
neutron beam focused on it. The activation of the boron-10 atom by a neutron
generates a lithium atom, a gamma ray, and an alpha particle, which can be used
to destroy tumor tissues. The aim of this work was to use BNNTs as a boron-10
carrier for BNCT and to demonstrate its potential. The nanomaterial was
characterized through XRD, FTIR, and SEM. The WST-8 assay was performed to
confirm the cell viability of BNNTs. The cells treated with BNNTs were irradiated
with the neutron beam of a Triga reactor, and the apoptosis caused by the
activation of the BNNTs was measured with a calcein AM/propidium iodide test. The
results demonstrate that this nanomaterial is a promising candidate for cancer
therapy through BNCT.
PMID- 28417904
TI - Zebrafish as an Alternative Vertebrate Model for Investigating Developmental
Toxicity-The Triadimefon Example.
AB - Triadimefon is a widely used triazole fungicide known to cause severe
developmental defects in several model organisms and in humans. The present study
evaluated in detail the developmental effects seen in zebrafish embryos exposed
to triadimefon, confirmed and expanded upon previous phenotypic findings and
compared them to those observed in other traditional animal models. In order to
do this, we exposed embryos to 2 and 4 ug/mL triadimefon and evaluated growth
until 120 h post-fertilization (hpf) through gross morphology examination. Our
analysis revealed significant developmental defects at the highest tested
concentration including somite deformities, severe craniofacial defects, a cleft
phenotype along the three primary neural divisions, a rigorously hypoplastic or
even absent mandible and a hypoplastic morphology of the pharyngeal arches.
Interestingly, massive pericardial edemas, abnormal shaped hearts, brachycardia
and inhibited or absent blood circulation were also observed. Our results
revealed that the presented zebrafish phenotypes are comparable to those seen in
other organism models and those derived from human observations as a result of
triadimefon exposure. We therefore demonstrated that zebrafish provide an
excellent system for study of compounds with toxic significance and can be used
as an alternative model for developmental toxicity studies to predict effects in
mammals.
PMID- 28417905
TI - Analytical Criticalities Associated to Different Immunological Methods for Serum
Free Light Chain Detection in Plasma Cell Dyscrasias: A Description of Particular
Clinical Cases.
AB - Current criteria for differential diagnosis of multiple myeloma (MM), Monoclonal
gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma
(SMM) are included in the 2003 guidelines by the International Myeloma Working
Group (IMWG). An updated version was then published in 2014, highlighting the
importance of serum free light chain (sFLC) detection, as well as the
kappa/lambda ratio as excellent indicators of clonality. At present, two
commercial assays for sFLC quantification are available: the FreeliteTM assay and
the N-Latex assay. The first was developed by The Binding Site based on a mixture
of polyclonal antibodies directed against a variety of FLC epitopes. It may be
run on a wide range of nephelometers, as well as on turbidimeters. The second
method was developed by Siemens and runs exclusively on Siemens instruments. It
employs a probe mixture of mouse monoclonal antibodies. The aim of our study was
to evaluate sFLC measurement and calculated kappa/lambda ratio in 85 patients
with monoclonal gammopathies (MGs) in order to compare methods. We demonstrated
that there is only a moderate concordance between the two FLC assays. In
particular, in one case, we observed no qualitative alterations of the serum
protein pattern, and in the absence of a FreeliteTM assay, sFLC measurement would
not have been possible to highlight the increase of lambda FLC.
PMID- 28417906
TI - Random Finite Set Based Bayesian Filtering with OpenCL in a Heterogeneous
Platform.
AB - While most filtering approaches based on random finite sets have focused on
improving performance, in this paper, we argue that computation times are very
important in order to enable real-time applications such as pedestrian detection.
Towards this goal, this paper investigates the use of OpenCL to accelerate the
computation of random finite set-based Bayesian filtering in a heterogeneous
system. In detail, we developed an efficient and fully-functional pedestrian
tracking system implementation, which can run under real-time constraints,
meanwhile offering decent tracking accuracy. An extensive evaluation analysis was
carried out to ensure the fulfillment of sufficient accuracy requirements. This
was followed by extensive profiling analysis to spot the potential bottlenecks in
terms of execution performance, which were then targeted to come up with an
OpenCL accelerated application. Video-throughput improvements from roughly 15 fps
to 100 fps (6*) were observed on average while processing typical MOT benchmark
videos. Moreover, the worst-case frame processing yielded an 18* advantage from
nearly 2 fps to 36 fps, thereby comfortably meeting the real-time constraints.
Our implementation is released as open-source code.
PMID- 28417907
TI - A Classification Method for Seed Viability Assessment with Infrared Thermography.
AB - This paper presents a viability assessment method for Pisum sativum L. seeds
based on the infrared thermography technique. In this work, different artificial
treatments were conducted to prepare seeds samples with different viability.
Thermal images and visible images were recorded every five minutes during the
standard five day germination test. After the test, the root length of each
sample was measured, which can be used as the viability index of that seed. Each
individual seed area in the visible images was segmented with an edge detection
method, and the average temperature of the corresponding area in the infrared
images was calculated as the representative temperature for this seed at that
time. The temperature curve of each seed during germination was plotted. Thirteen
characteristic parameters extracted from the temperature curve were analyzed to
show the difference of the temperature fluctuations between the seeds samples
with different viability. With above parameters, support vector machine (SVM) was
used to classify the seed samples into three categories: viable, aged and dead
according to the root length, the classification accuracy rate was 95%. On this
basis, with the temperature data of only the first three hours during the
germination, another SVM model was proposed to classify the seed samples, and the
accuracy rate was about 91.67%. From these experimental results, it can be seen
that infrared thermography can be applied for the prediction of seed viability,
based on the SVM algorithm.
PMID- 28417909
TI - Interactions among the Predatory Midge Aphidoletes aphidimyza (Diptera:
Cecidomyiidae), the Fungal Pathogen Metarhizium brunneum (Ascomycota:
Hypocreales), and Maize-Infesting Aphids in Greenhouse Mesocosms.
AB - The generalist entomopathogenic fungus, Metarhizium brunneum, has proved to have
great potential as a versatile biological pest control agent. The gall midge
Aphidoletes aphidimyza is a specialist predator that occurs naturally in Europe
and has been successfully used for aphid suppression. However, the interaction
between these two biological control organisms and how it may affect the
biological control of aphids awaits further investigation. As part of the EU
supported project INBIOSOIL, this study was conducted in greenhouse conditions to
assess the possible effects of combining both biological control agents. In a
randomized complete block design, sweet corn (Zea mays var. saccharata) plants
were grown in large pots filled with natural soil or natural soil inoculated with
M. brunneum. At the third leaf stage, before being individually caged, plants
were infested with Rhopalosiphum padi and A. aphidimyza pupae were introduced in
the soil. Aphidoletes aphidimyza midge emergence, number of living midges and
number of aphids were recorded daily. The presence of conidia in the soil and on
leaves was assessed during the experiment. At the conclusion of the experiment,
the number of live aphids and their developmental stage, consumed aphids, and A.
aphidimyza eggs was assessed under stereomicroscope. This study's findings showed
that the presence of M. brunneum did not affect A. aphidimyza midge emergence.
However, longevity was significantly affected. As the study progressed,
significantly fewer predatory midges were found in cages treated with M. brunneum
compared to untreated cages. Furthermore, by the end of the study, the number of
predatory midges found in the Metarhizium-treated cages was four times lower than
in the untreated cages. Both daily and final count of aphids were significantly
affected by treatment. Aphidoletes aphidimyza applied alone suppressed the aphid
population more effectively than M. brunneum applied alone. Additionally, the
aphid population was most suppressed when both agents were combined, though the
suppression was less than additive.
PMID- 28417908
TI - Cytokinesis Failure Leading to Chromosome Instability in v-Src-Induced
Oncogenesis.
AB - v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active
variant of c-Src. Activation of Src is observed frequently in colorectal and
breast cancers, and is critical in tumor progression through multiple processes.
However, in some experimental conditions, v-Src causes growth suppression and
apoptosis. In this review, we highlight recent progress in our understanding of
cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src
expressing cells. v-Src induces cell cycle changes-such as the accumulation of
the 4N cell population-and increases the number of binucleated cells, which is
accompanied by an excess number of centrosomes. Time-lapse analysis of v-Src
expressing cells showed that cytokinesis failure is caused by cleavage furrow
regression. Microscopic analysis revealed that v-Src induces delocalization of
cytokinesis regulators including Aurora B and Mklp1. Tetraploid cell formation is
one of the causes of chromosome instability; however, tetraploid cells can be
eliminated at the tetraploidy checkpoint. Interestingly, v-Src weakens the
tetraploidy checkpoint by inhibiting the nuclear exclusion of the transcription
coactivator YAP, which is downstream of the Hippo pathway and its nuclear
exclusion is critical in the tetraploidy checkpoint. We also discuss the
relationship between v-Src-induced chromosome instability and growth suppression
in v-Src-induced oncogenesis.
PMID- 28417910
TI - Effects of Three Commercially Available Sports Drinks on Substrate Metabolism and
Subsequent Endurance Performance in a Postprandial State.
AB - Purpose: To examine the effects of commercially available sports beverages with
various components on substrate metabolism and subsequent performance. Methods:
Two studies were conducted in a double-blinded, counterbalanced manner. Study I
was designed to determine the glycemic index, while study II determined the
utilization of substrates and subsequent exercise performance. Ten healthy male
participants (age 21.70 +/- 2.41 years, height 176.60 +/- 5.23 cm, weight 66.58
+/- 5.38 kg, VO2max 48.1 +/- 8.4 mL/kg/min) participated in both study I and
study II. Three types of commercially available sports beverage powders were
used. The powders consisted primarily of oligosaccharides (low molecular weight
carbohydrates, L-CHO), hydrolyzed starch (high molecular weight CHO, H-CHO), and
whey protein powder with carbohydrate (CHO-PRO). They were dissolved in purified
water with identical CHO concentration of 8% (w/v). In study I, each participant
underwent two oral glucose tolerance tests (OGTT) and one glycemic response test
for each sports drink. In study II, participants cycled for 60 min at 70% VO2max,
one hour after consuming a standardized breakfast. One of four prescribed
beverages (L-CHO, H-CHO, CHO-PRO, and Placebo control, PLA) was served at 0, 15,
30, 45 min during the exercise. Six hours after the first exercise session,
participants came back for a "time to exhaustion test" (TTE). Blood samples were
drawn at 0, 30, and 60 min in the first exercise session, while arterial blood
gas analysis was conducted at 0, 30, and 60 min in both sessions. Subjective
feelings (rating of perceived exertion and abdominal discomfort) were also
evaluated every 30 min during exercise. Results: Compared to the reference
standardized glucose solution, the glycemic index of the L-CHO beverage was
117.70 +/- 14.25, while H-CHO was 105.50 +/- 12.82, and CHO-PRO was 67.23 +/-
5.88. During the exercise test, the insulin level at 30 and 60 min was
significantly lower than baseline following the treatment of L-CHO, H-CHO, and
PLA (p < 0.05). The CHO oxidation rate at 60 min in the first exercise session
was significantly higher than that at 60 min in the second exercise session
following the L-CHO treatment (p < 0.05). Time to exhaustion was not
significantly different (p > 0.05). Conclusion: The CHO sports beverage with
additional PRO maintains insulin production during endurance cycling at 70%
VO2max in the postprandial state. L-CHO sports beverage suppresses fat
utilization during the subsequent exercise performance test. The subsequent
exercise performance (as evaluated by TTE) was not influenced by the type of CHO
or the addition of PRO in the commercially available sports beverages used in the
present study.
PMID- 28417911
TI - Genome-Wide Analyses of the Soybean F-Box Gene Family in Response to Salt Stress.
AB - The F-box family is one of the largest gene families in plants that regulate
diverse life processes, including salt responses. However, the knowledge of the
soybean F-box genes and their roles in salt tolerance remains limited. Here, we
conducted a genome-wide survey of the soybean F-box family, and their expression
analysis in response to salinity via in silico analysis of online RNA-sequencing
(RNA-seq) data and quantitative reverse-transcription polymerase chain reaction
(qRT-PCR) to predict their potential functions. A total of 725 potential F-box
proteins encoded by 509 genes were identified and classified into 9 subfamilies.
The gene structures, conserved domains and chromosomal distributions were
characterized. There are 76 pairs of duplicate genes identified, including genome
wide segmental and tandem duplication events, which lead to the expansion of the
number of F-box genes. The in silico expression analysis showed that these genes
would be involved in diverse developmental functions and play an important role
in salt response. Our qRT-PCR analysis confirmed 12 salt-responding F-box genes.
Overall, our results provide useful information on soybean F-box genes,
especially their potential roles in salt tolerance.
PMID- 28417912
TI - Electrospun Fiber Pads of Cellulose Acetate and Essential Oils with Antimicrobial
Activity.
AB - The method of electrospinning was used to create nanofibers made of cellulose
acetate (CA) and essential oils (EOs). CA polymer at 15% w/v was dissolved in
acetone and then 1% or 5% v/v of EOs was added to the polymer solution. The
utilized essential oils were rosemary and oregano oils. Then, the CA/EOs in
acetone solution were electrospun, creating micro/nanofibers, approximately 700
1500 nm in diameter. Raman spectroscopy was used to detect the attachment of the
EOs in the CA electrospun fibers (ESFs). Scanning electron microscopy was used to
study the morphology, topography and dimensions of the ESFs. The formed CA/EOs
ESFs are found to have good antimicrobial properties against three common
microbial species, frequently found in difficult to treat infections: Bacteria
species Staphylococcus aureus, Escherichia coli and the yeast Candida albicans.
ESFs with 5% v/v oregano oil with respect to the initial solution, showed the
best antimicrobial and anti-biofilm effects due to the potency of this EO against
bacteria and fungi, especially for Escherichia coli and Candida albicans. This
work describes an effective and simple method to prepare CA/EOs ESFs and opens up
many new applications of micro/nanofibers such as improved antimicrobial wound
dressings, anti-biofilm surfaces, sensors and packaging alternatives.
PMID- 28417913
TI - Comparative Study on the Antivirus Activity of Shuang-Huang-Lian Injectable
Powder and Its Bioactive Compound Mixture against Human Adenovirus III In Vitro.
AB - Shuang-Huang-Lian injectable powder (SHL)-a classical purified herbal preparation
extracted from Scutellaria baicalensis, Lonicera japonica, and Forsythia suspense
has been used against human adenovirus III (HAdV3) for many years. The
combination herb and its major bioactive compounds, including chlorogenic acid,
baicalin, and forsythia glycosides A, are effective inhibitors of the virus.
However, no comprehensive studies are available on the antiviral effects of SHL
against HAdV3. Moreover, it remains unclear whether the mixture of chlorogenic
acid, baicalin, and forsythia glycosides A (CBF) has enhanced antiviral activity
compared with SHL. Therefore, a comparative study was performed to investigate
the combination which is promising for further antiviral drug development. To
evaluate their antivirus activity in parallel, the combination ratio and dose of
CBF were controlled and consistent with SHL. First, the fingerprint and the ratio
of CBF in SHL were determined by high performance liquid chromatography. Then, a
plaque reduction assay, reverse transcription polymerase chain reaction (PCR),
real-time polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay
(ELISA) were used to explore its therapeutic effects on viral infection and
replication, respectively. The results showed that SHL and CBF inhibited dose-
and time-dependently HAdV3-induced plaque formation in A549 and HEp-2 cells. SHL
was more effective than CBF when supplemented prior to and after viral
inoculation. SHL prevented viral attachment, internalization, and replication at
high concentration and decreased viral levels within and out of cells at non
toxic concentrations in both cell types. Moreover, the expression of tumor
necrosis factor alpha (TNF)-alpha, interleukin (IL)-1beta, and IL-6 was lower and
the expression of interferon (IFN)-gamma was higher in both cell types treated
with SHL than with CBF. In conclusion, SHL is much more effective and slightly
less toxic than CBF.
PMID- 28417914
TI - Interactions of the Insulin-Like Growth Factor Axis and Vitamin D in Prostate
Cancer Risk in the Prostate Cancer Prevention Trial.
AB - Some, but not all, epidemiologic studies report an association between vitamin D
and prostate cancer risk. The inconsistent findings might be explained in the
context of modification by members of the insulin-like growth factor (IGF) axis.
Data and specimens for this nested case-control study (n = 1695 cases and n =
1682 controls) are from the Prostate Cancer Prevention Trial (PCPT). Baseline
serum samples were assayed for 25(OH)D, IGF-1, IGF-2, IGFBP-2, IGFBP-3, and the
ratio of IGF1:BP3, along with insulin-related markers c-peptide and leptin. The
presence of prostate cancer was assessed by prostate biopsy. Multivariate
logistic regression was used to estimate odds ratios (OR) and 95% confidence
intervals (CIs) for prostate cancer risk. There were no interactions between
serum 25(OH)D and IGF analytes in relation to prostate cancer risk when PCPT
treatment arms were combined. In the placebo arm, above median serum 25(OH)D
levels were associated with increased risk of prostate cancer among men with
higher IGF-2 (OR:1.33, 95% CI: 1.00-1.65), with a significant interaction between
25(OH)D and treatment arm (Pinteraction = 0.04). Additionally, there was an
interaction between treatment arm and serum IGFBP-3 (Pinteraction = 0.03). Higher
serum 25(OH)D may increase risk of prostate cancer in the presence of higher
circulating IGF-2.
PMID- 28417915
TI - High Glucose Accelerates Cell Proliferation and Increases the Secretion and mRNA
Expression of Osteopontin in Human Pancreatic Duct Epithelial Cells.
AB - BACKGROUND: The incidence of pancreatic cancer is increasing year-by-year in
Japan. Among the diseases that complicate pancreatic cancer, diabetes is the most
common. Recently, it has become evident that patients suffering from diabetes and
obesity show increased expression of osteopontin (OPN). The purpose of this study
was to investigate the effect of high glucose and high insulin culture conditions
on a human pancreatic duct epithelial cell line (HPDE-6), focusing particularly
on OPN expression. METHODS: HPDE-6 were cultured under various conditions,
employing several combinations of glucose (normal, 6 mM high, 30 mM, and 60 mM)
and insulin (0.1 nM, 1 nM) concentration. RESULTS: HPDE-6 cell proliferation was
significantly accelerated under high glucose culture conditions in comparison to
samples in 6 mM glucose, and was more prominent under high insulin conditions. At
the same time, the expression of OPN mRNA was also increased significantly. In
comparison with 6 mM glucose, the expression of 8-OHdG DNA was increased in high
glucose culture. CONCLUSION: HPDE-6 cells show accelerated proliferation and
increased OPN expression when cultured under high glucose and high insulin
conditions. Furthermore, the cells show increased oxidative stress in the
presence of high glucose.
PMID- 28417916
TI - Metallothionein Gene Family in the Sea Urchin Paracentrotus lividus: Gene
Structure, Differential Expression and Phylogenetic Analysis.
AB - Metallothioneins (MT) are small and cysteine-rich proteins that bind metal ions
such as zinc, copper, cadmium, and nickel. In order to shed some light on MT gene
structure and evolution, we cloned seven Paracentrotus lividus MT genes,
comparing them to Echinodermata and Chordata genes. Moreover, we performed a
phylogenetic analysis of 32 MTs from different classes of echinoderms and 13 MTs
from the most ancient chordates, highlighting the relationships between them.
Since MTs have multiple roles in the cells, we performed RT-qPCR and in situ
hybridization experiments to understand better MT functions in sea urchin
embryos. Results showed that the expression of MTs is regulated throughout
development in a cell type-specific manner and in response to various metals. The
MT7 transcript is expressed in all tissues, especially in the stomach and in the
intestine of the larva, but it is less metal-responsive. In contrast, MT8 is
ectodermic and rises only at relatively high metal doses. MT5 and MT6 expression
is highly stimulated by metals in the mesenchyme cells. Our results suggest that
the P. lividus MT family originated after the speciation events by gene
duplications, evolving developmental and environmental sub-functionalization.
PMID- 28417917
TI - Minicircle Mediated Gene Delivery to Canine and Equine Mesenchymal Stem Cells.
AB - Gene-directed tissue repair offers the clinician, human or veterinary, the chance
to enhance cartilage regeneration and repair at a molecular level. Non-viral
plasmid vectors have key biosafety advantages over viral vector systems for
regenerative therapies due to their episomal integration however, conventional
non-viral vectors can suffer from low transfection efficiency. Our objective was
to identify and validate in vitro a novel non-viral gene expression vector that
could be utilized for ex vivo and in vivo delivery to stromal-derived mesenchymal
stem cells (MSCs). Minicircle plasmid DNA vector containing green fluorescent
protein (GFP) was generated and transfected into adipose-derived MSCs from three
species: canine, equine and rodent and transfection efficiency was determined.
Both canine and rat cells showed transfection efficiencies of approximately 40%
using minicircle vectors with equine cells exhibiting lower transfection
efficiency. A Sox9-expressing minicircle vector was generated and transfected
into canine MSCs. Successful transfection of the minicircle-Sox9 vector was
confirmed in canine cells by Sox9 immunostaining. This study demonstrate the
application and efficacy of a novel non-viral expression vector in canine and
equine MSCs. Minicircle vectors have potential use in gene-directed regenerative
therapies in non-rodent animal models for treatment of cartilage injury and
repair.
PMID- 28417919
TI - SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of
Prostate Cancer Cells via Regulating SMAD4 deSUMOylation.
AB - In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific
cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in
regulating deSUMOylation of TGF-beta/SMADs signaling is unknown. In this study,
we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate
cancer cells with high metastatic characteristics (PC3M). Likewise, we also
created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate
cancer cells with low metastatic potential (LNCaP). We showed that silencing of
SENP1 promoted cellular apoptosis, and inhibited proliferation and migration of
PC3M cells. Moreover, SENP1 silencing increased the SMAD4 expression at protein
level, up-regulated E-cadherin and down-regulated Vimentin expression, indicating
the inhibition of epithelial mesenchymal transition (EMT). Furthermore, SMAD4
interference abolished SENP1-mediated up-regulation of E-cadherin, suggesting
that SENP1 regulated E-cadherin expression via SMAD4. SENP1 over-expression in
LNCaP cells reduced SMAD4 protein, and promoted EMT via decreasing E-cadherin and
increasing Vimentin. Moreover, down-regulation of SMAD4 and E-cadherin were
blocked, after transfection with two SUMOylation sites mutated SMAD4, suggesting
that SENP1 might reduce SMAD4 levels to regulate E-cadherin expression via
deSUMOylation of SMAD4. In conclusion, SENP1 deSUMOylated SMAD4 to promote EMT
via up-regulating E-cadherin in prostate cancer cells. Therefore, SENP1 is a
potential target for treatment of advanced prostate cancer.
PMID- 28417918
TI - High Prevalence of blaNDM-1, blaVIM, qacE, and qacEDelta1 Genes and Their
Association with Decreased Susceptibility to Antibiotics and Common Hospital
Biocides in Clinical Isolates of Acinetobacter baumannii.
AB - The objective of this study was to evaluate the susceptibility of metallo-beta
lactamase (MBL)-producing Acinetobacter baumannii (A. baumannii) clinical
isolates to biocides. We also determined the prevalence and correlation of efflux
pump genes, class 1 integron and MBL encoding genes. In addition, blaVIM, blaNDM
1, qacE and qacEDelta1 nucleotide sequence analysis was performed and compared to
sequences retrieved from GenBank at the National Center for Biotechnology
Information database. A. baumannii had a resistance rate to carbapenem of 71.4%
and 39.3% and was found to be a MBL producer. The minimum inhibitory
concentrations (MICs) of chlorhexidine and cetrimide were higher than the
recommended concentrations for disinfection in 54.5% and 77.3% of MBL-positive
isolates respectively and their MICs were significantly higher among qac gene
positive isolates. Coexistence of qac genes was detected in 68.1% and 50% of the
isolates with blaVIM and blaNDM-1 respectively. There was a significant
correlation between the presence of qac genes and MBL-encoding blaVIM and blaNDM
1 genes. Each of the blaNDM-1, blaVIM, qacE and qacEDelta1 DNA sequences showed
homology with each other and with similar sequences reported from other
countries. The high incidence of Verona integron-encoded metallo-beta-lactamases
(VIM) and New-Delhi-metallo-beta-lactamase (NDM) and qac genes in A.baumannii
highlights emerging therapeutic challenges for being readily transferable between
clinically relevant bacteria. In addition reduced susceptibility to chlorhexidine
and cetrimide and the potential for cross resistance to some antibiotics
necessitates the urgent need for healthcare facilities to periodically evaluate
biocides efficacy, to address the issue of antiseptic resistance and to initiate
a "biocidal stewardship".
PMID- 28417920
TI - Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human
Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study
and Hepatotoxicity in Humans.
AB - In the development of drugs, we sometimes encounter fatty change of the
hepatocytes (steatosis) which is not accompanied by degenerative change in the
liver in non-clinical toxicity studies. In this study, we investigated the
relationships between fatty change of the hepatocytes noted in non-clinical
toxicity studies of compound X, a candidate compound in drug development, and
mitochondrial dysfunction in order to estimate the potential risk of the compound
to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in
vitro exploratory studies for this purpose. In vivo lipidomics analysis was
conducted to investigate the relationships between alteration of the hepatic
lipids and mitochondrial dysfunction. In the liver of rats treated with compound
X, triglycerides containing long-chain fatty acids, which are the main energy
source of the mitochondria, accumulated. Accumulation of these triglycerides was
considered to be related to the inhibition of mitochondrial respiration based on
the results of in vitro mitochondria toxicity studies. In conclusion, fatty
change of the hepatocytes (steatosis) in non-clinical toxicity studies of drug
candidates can be regarded as a critical finding for the estimation of their
potential risk to induce DILI in humans when the fatty change is induced by
mitochondrial dysfunction.
PMID- 28417921
TI - Bioethics of Clinical Applications of Stem Cells.
AB - The clinical applications of stem cells pose a multitude of problems, including
safety, efficacy, information and consent, the right to unproven treatments, the
"right to try", costs, access, sustainability, scientific scrupulousness, patents
and regulatory aspects, to name but a few. This article does not address
individual issues, but rather introduces and discusses some of the possible
approaches to solving the problems. The first part compares the consequentialist
and deontological approaches, offering an overview of "top-down" and "bottom-up"
models and proposing the principles of personalism as applied in clinical
settings. The second part of the article suggests practical frameworks for
organising the ethical issues, focusing in particular on the medical indications,
patient preferences, quality of life, and contextual features.
PMID- 28417922
TI - Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit
Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes.
AB - Seaweed, a popular and abundant food ingredient mainly consumed in Asian
countries, is a good source of bioactive compounds with anti-obesity effects.
However, the anti-obesity effects of Sargassum thunbergii have not yet been
established. In this study, we isolated six indole derivatives (STCs)-indole-2
carboxaldehyde (STC-1), indole-3-carboxaldehyde (STC-2), indole-4-carboxaldehyde
(STC-3), indole-5-carboxaldehyde (STC-4), indole-6-carboxaldehyde (STC-5), and
indole-7-carboxaldehyde (STC-6)-from S. thunbergii and evaluated their inhibitory
effects on adipocyte differentiation in 3T3-L1 cells. We found that STC-1 and STC
5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes
and thus selected these compounds for further study. STC-1 and STC-5
significantly inhibited lipid accumulation and downregulated the expression of
peroxisome proliferator-activated receptor-gamma (PPARgamma), CCAAT/enhancer
binding protein alpha (C/EBPalpha), and sterol regulatory element-binding protein
1c (SREBP-1c) in a dose-dependent manner. The specific mechanism mediating the
effects of STC-1 and STC-5 was shown to be AMP-activated protein kinase (AMPK)
activation. Our results demonstrated the inhibitory effect of STC-1 and STC-5 on
adipogenesis through the activation of the AMPK signal pathway. Together, these
findings suggested that STC-1 and STC-5 may be effective candidates for the
prevention of obesity or obesity-related diseases.
PMID- 28417923
TI - Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker.
AB - Kawasaki disease (KD) is an autoimmune-like disease and acute childhood
vasculitis syndrome that affects various systems but has unknown etiology. In
addition to the standard diagnostic criteria, anemia is among the most common
clinical features of KD patients and is thought to have a more prolonged duration
of active inflammation. In 2001, the discovery of a liver-derived peptide hormone
known as hepcidin began revolutionizing our understanding of anemia's relation to
a number of inflammatory diseases, including KD. This review focuses on hepcidin
induced iron deficiency's relation to transient hyposideremia, anemia, and
disease outcomes in KD patients, and goes on to suggest possible routes of
further study.
PMID- 28417925
TI - A Cost-Effective Geodetic Strainmeter Based on Dual Coaxial Cable Bragg Gratings.
AB - Observations of surface deformation are essential for understanding a wide range
of geophysical problems, including earthquakes, volcanoes, landslides, and
glaciers. Current geodetic technologies, such as global positioning system (GPS),
interferometric synthetic aperture radar (InSAR), borehole and laser
strainmeters, are costly and limited in their temporal or spatial resolutions.
Here we present a new type of strainmeters based on the coaxial cable Bragg
grating (CCBG) sensing technology that provides cost-effective strain
measurements. Two CCBGs are introduced into the geodetic strainmeter: one serves
as a sensor to measure the strain applied on it, and the other acts as a
reference to detect environmental noises. By integrating the sensor and reference
signals in a mixer, the environmental noises are minimized and a lower mixed
frequency is obtained. The lower mixed frequency allows for measurements to be
taken with a portable spectrum analyzer, rather than an expensive spectrum
analyzer or a vector network analyzer (VNA). Analysis of laboratory experiments
shows that the strain can be measured by the CCBG sensor, and the portable
spectrum analyzer can make measurements with the accuracy similar to the
expensive spectrum analyzer, whose relative error to the spectrum analyzer R3272
is less than +/-0.4%. The outputs of the geodetic strainmeter show a linear
relationship with the strains that the CCBG sensor experienced. The measured
sensitivity of the geodetic strainmeter is about -0.082 kHz/MUepsilon; it can
cover a large dynamic measuring range up to 2%, and its nonlinear errors can be
less than 5.3%.
PMID- 28417924
TI - Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells
after Xenograft into Nude Mice.
AB - The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian
tumors resides in a tiny population of cancer cells known as ovarian cancer stem
cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a
great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles
(PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX)
against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an
emulsion solvent evaporation method, supported by incorporation of folic acid
(FA) as the ligand. NPs were characterized for size, surface morphology, drug
loading, and encapsulation efficiency. In vitro cytotoxicity of PTX-loaded
FA/PLGA NPs was tested against OCSCs with MTT assay. In vivo anti-tumoral
efficiency and active targeting potential of prepared NPs against tumors in nude
mice were investigated. In vitro results revealed that IC50 of PTX was
significantly reduced after loading on PLGA NPs. On the other hand, in vivo
results showed that PLGA NPs enhanced the tumor suppression efficiency of PTX.
Investigation with real time quantitative PCR analysis revealed the limiting
expression of chemo-resistant genes (ABCG2 and MDR1) after applying PLGA NPs as a
drug delivery system for PTX. Histopathological examination of tumors showed the
effective biological influence of PTX-loaded FA/PLGA NPs through the appearance
of reactive lymphoid follicles. Targeting potential of PTX was activated by
FA/PLGA NPs through significant preservation of body weight (p < 0.0001) and
minimizing the systemic toxicity in healthy tissues. Immunohistochemical
investigation revealed a high expression of apoptotic markers in tumor tissue,
supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on
FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting
potential against OCSCs.
PMID- 28417926
TI - Fast Noncircular 2D-DOA Estimation for Rectangular Planar Array.
AB - A novel scheme is proposed for direction finding with uniform rectangular planar
array. First, the characteristics of noncircular signals and Euler's formula are
exploited to construct a new real-valued rectangular array data. Then, the
rotational invariance relations for real-valued signal space are depicted in a
new way. Finally the real-valued propagator method is utilized to estimate the
pairing two-dimensional direction of arrival (2D-DOA). The proposed algorithm
provides better angle estimation performance and can discern more sources than
the 2D propagator method. At the same time, it has very close angle estimation
performance to the noncircular propagator method (NC-PM) with reduced
computational complexity.
PMID- 28417927
TI - Wireless Fractal Ultra-Dense Cellular Networks.
AB - With the ever-growing number of mobile devices, there is an explosive expansion
in mobile data services. This represents a challenge for the traditional cellular
network architecture to cope with the massive wireless traffic generated by
mobile media applications. To meet this challenge, research is currently focused
on the introduction of a small cell base station (BS) due to its low transmit
power consumption and flexibility of deployment. However, due to a complex
deployment environment and low transmit power of small cell BSs, the coverage
boundary of small cell BSs will not have a traditional regular shape. Therefore,
in this paper, we discuss the coverage boundary of an ultra-dense small cell
network and give its main features: aeolotropy of path loss fading and fractal
coverage boundary. Simple performance analysis is given, including coverage
probability and transmission rate, etc., based on stochastic geometry theory and
fractal theory. Finally, we present an application scene and discuss challenges
in the ultra-dense small cell network.
PMID- 28417929
TI - Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction
of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in
Thyroid Cancer.
AB - : Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the
context of thyroid cancer for identification of the optimal treatment strategy.
It has exemplarily been shown that DWI at 3T can distinguish undifferentiated
from well-differentiated thyroid carcinoma, which has decisive implications for
the magnitude of surgery. This study used DWI histogram analysis of whole tumor
apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate
thyroid carcinomas which had already gained the capacity to metastasize
lymphatically from those not yet being able to spread via the lymphatic system.
The secondary aim was to reflect prognostically important tumor-biological
features like cellularity and proliferative activity with ADC histogram analysis.
Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph
node status, extent of infiltration of surrounding tissue, and Ki-67 and p53
expression were assessed in these patients. DWI was obtained in a 3T system using
b values of 0, 400, and 800 s/mm2. Whole tumor ADC volumes were analyzed using a
histogram-based approach. Several ADC parameters showed significant correlations
with immunohistopathological parameters. Most importantly, ADC histogram skewness
and ADC histogram kurtosis were able to differentiate between nodal negative and
nodal positive thyroid carcinoma. CONCLUSIONS: histogram analysis of whole ADC
tumor volumes has the potential to provide valuable information on tumor biology
in thyroid carcinoma. However, further studies are warranted.
PMID- 28417930
TI - Degradation of Methyl 2-Aminobenzoate (Methyl Anthranilate) by H2O2/UV: Effect of
Inorganic Anions and Derived Radicals.
AB - This study shows that methyl 2-aminobenzoate (also known as methyl anthranilate,
hereafter MA) undergoes direct photolysis under UVC and UVB irradiation and that
its photodegradation is further accelerated in the presence of H2O2. Hydrogen
peroxide acts as a source of hydroxyl radicals (.OH) under photochemical
conditions and yields MA hydroxyderivatives. The trend of MA photodegradation
rate vs. H2O2 concentration reaches a plateau because of the combined effects of
H2O2 absorption saturation and .OH scavenging by H2O2. The addition of chloride
ions causes scavenging of .OH, yielding Cl2.- as the most likely reactive
species, and it increases the MA photodegradation rate at high H2O2 concentration
values. The reaction between Cl2.- and MA, which has second-order rate constant k
C l 2 * - + M A = (4.0 +/- 0.3) * 108 M-1.s-1 (determined by laser flash
photolysis), appears to be more selective than the .OH process in the presence of
H2O2, because Cl2.- undergoes more limited scavenging by H2O2 compared to .OH.
While the addition of carbonate causes .OH scavenging to produce CO3.- ( k C O 3
* - + M A = (3.1 +/- 0.2) * 108 M-1.s-1), carbonate considerably inhibits the
photodegradation of MA. A possible explanation is that the elevated pH values of
the carbonate solutions make H2O2 to partially occur as HO2-, which reacts very
quickly with either .OH or CO3.- to produce O2.-. The superoxide anion could
reduce partially oxidised MA back to the initial substrate, with consequent
inhibition of MA photodegradation. Fast MA photodegradation is also observed in
the presence of persulphate/UV, which yields SO4.- that reacts effectively with
MA ( k S O 4 * - + M A = (5.6 +/- 0.4) * 108 M-1.s-1). Irradiated H2O2 is
effective in photodegrading MA, but the resulting MA hydroxyderivatives are
predicted to be about as toxic as the parent compound for aquatic organisms (most
notably, fish and crustaceans).
PMID- 28417928
TI - Potential Coagulation Factor-Driven Pro-Inflammatory Responses in Ovarian Cancer
Tissues Associated with Insufficient O2 and Plasma Supply.
AB - Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII).
The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic
blood coagulation process. Interactions between cancer cells and immune cells via
coagulation factors and adhesion molecules can promote progression of cancer,
including epithelial ovarian cancer (EOC). This process is not necessarily
advantageous, as tumor tissues generally undergo hypoxia due to aberrant
vasculature, followed by reduced access to plasma components such as coagulation
factors. However, hypoxia can activate TF expression. Expression of fVII,
intercellular adhesion molecule-1 (ICAM-1), and multiple pro-inflammatory
cytokines can be synergistically induced in EOC cells in response to hypoxia
along with serum deprivation. Thus, pro-inflammatory responses associated with
the TF-fVIIa-ICAM-1 interaction are expected within hypoxic tissues. Tumor tissue
consists of multiple components such as stromal cells, interstitial fluid,
albumin, and other micro-factors such as proton and metal ions. These factors,
together with metabolism reprogramming in response to hypoxia and followed by
functional modification of TF, may contribute to coagulation factor-driven
inflammatory responses in EOC tissues. The aim of this review was to describe
potential coagulation factor-driven inflammatory responses in hypoxic EOC
tissues. Arguments were extended to clinical issues targeting this characteristic
tumor environment.
PMID- 28417931
TI - Upstreaming and Normalizing Advance Care Planning Conversations-A Public Health
Approach.
AB - As a society, we simply don't talk about this universal experience called dying
and death; in fact, we ignore it until we have to face it. Thus, it is often in a
crisis experience when we have to make decisions while we are laden with
uncertainty and intense emotions. Sixty percent of people say making sure their
family is not burdened by tough decisions is extremely important, yet 56% of them
have not held a conversation about its context. Instead of waiting to make end-of
life decisions, let us begin to think about what matters most while we are
living, what we value most, and how we translate these values into conversations
about what is important. As a public health concern, if we can upstream the
advance care planning discussion into usual health promotion activities, perhaps,
as a society, we can begin to normalize and reshape how we make decisions about
the last chapters of our lives.
PMID- 28417932
TI - Marine Microbial-Derived Molecules and Their Potential Use in Cosmeceutical and
Cosmetic Products.
AB - The oceans encompass a wide range of habitats and environmental conditions, which
host a huge microbial biodiversity. The unique characteristics of several marine
systems have driven a variety of biological adaptations, leading to the
production of a large spectrum of bioactive molecules. Fungi, fungi-like protists
(such as thraustochytrids) and bacteria are among the marine organisms with the
highest potential of producing bioactive compounds, which can be exploited for
several commercial purposes, including cosmetic and cosmeceutical ones.
Mycosporines and mycosporine-like amino acids, carotenoids, exopolysaccharides,
fatty acids, chitosan and other compounds from these microorganisms might
represent a sustainable, low-cost and fast-production alternative to other
natural molecules used in photo-protective, anti-aging and skin-whitening
products for face, body and hair care. Here, we review the existing knowledge of
these compounds produced by marine microorganisms, highlighting the marine
habitats where such compounds are preferentially produced and their potential
application in cosmetic and cosmeceutical fields.
PMID- 28417933
TI - Radiogenomic Analysis of Oncological Data: A Technical Survey.
AB - In the last few years, biomedical research has been boosted by the technological
development of analytical instrumentation generating a large volume of data. Such
information has increased in complexity from basic (i.e., blood samples) to
extensive sets encompassing many aspects of a subject phenotype, and now rapidly
extending into genetic and, more recently, radiomic information. Radiogenomics
integrates both aspects, investigating the relationship between imaging features
and gene expression. From a methodological point of view, radiogenomics takes
advantage of non-conventional data analysis techniques that reveal meaningful
information for decision-support in cancer diagnosis and treatment. This survey
is aimed to review the state-of-the-art techniques employed in radiomics and
genomics with special focus on analysis methods based on molecular and multimodal
probes. The impact of single and combined techniques will be discussed in light
of their suitability in correlation and predictive studies of specific oncologic
diseases.
PMID- 28417934
TI - Expression of Adenosine A2B Receptor and Adenosine Deaminase in Rabbit Gastric
Mucosa ECL Cells.
AB - Adenosine is readily available to the glandular epithelium of the stomach. Formed
continuously in intracellular and extracellular locations, it is notably produced
from ATP released in enteric cotransmission. Adenosine analogs modulate chloride
secretion in gastric glands and activate acid secretion in isolated parietal
cells through A2B adenosine receptor (A2BR) binding. A functional link between
surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but
whether this connection is a general feature of gastric mucosa cells is unknown.
Here we examine whether A2BR is expressed at the membrane of histamine-producing
enterochromaffin-like (ECL) cells, the major endocrine cell type in the oxyntic
mucosa, and if so, whether it has a vicinity relationship with ADA. We used a
highly homogeneous population of rabbit ECL cells (size 7.5-10 um) after
purification by elutriation centrifugation. The surface expression of A2BR and
ADA proteins was assessed by flow cytometry and confocal microscopy. Our findings
demonstrate that A2BR and ADA are partially coexpressed at the gastric ECL cell
surface and that A2BR is functional, with regard to binding of adenosine analogs
and adenylate cyclase activation. The physiological relevance of A2BR and ADA
association in regulating histamine release is yet to be explained.
PMID- 28417935
TI - Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid
Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment
of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA
Specimens.
AB - Molecular markers are helpful diagnostic tools, particularly for cytologically
indeterminate thyroid nodules. Preoperative RET/PTC1 rearrangement analysis in
BRAF and RAS wild-type indeterminate thyroid nodules would permit the formulation
of an unambiguous surgical plan. Cycle threshold values according to the cell
count for detection of the RET/PTC1 rearrangement by real-time reverse
transcription-polymerase chain reaction (RT-PCR) using fresh and routine air
dried TPC1 cells were evaluated. The correlation of RET/PTC1 rearrangement
between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded
(FFPE) specimens was analyzed. RET/PTC1 rearrangements of 76 resected BRAF and
RAS wild-type classical PTCs were also analyzed. Results of RT-PCR and the
Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used,
expression of RET/PTC1 rearrangement was detectable after 35 and 33 PCR cycles,
respectively. The results of RET/PTC1 rearrangement in 10 FNA and paired FFPE
papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty
nine (38.2%) of 76 BRAF and RAS wild-type classical PTCs had RET/PTC1
rearrangement. Comparison of RET/PTC1 rearrangement analysis between RT-PCR and
the Nanostring showed moderate agreement with a kappa value of 0.56 (p = 0.002).
The RET/PTC1 rearrangement analysis by RT-PCR using routine air-dried FNA
specimen was confirmed to be technically applicable. A significant proportion
(38.2%) of the BRAF and RAS wild-type PTCs harbored RET/PTC1 rearrangements.
PMID- 28417936
TI - Oncolytic Alphaviruses in Cancer Immunotherapy.
AB - Oncolytic viruses show specific targeting and killing of tumor cells and
therefore provide attractive assets for cancer immunotherapy. In parallel to
oncolytic viral vectors based on adenoviruses and herpes simplex viruses,
oncolytic RNA viruses and particularly alphaviruses have been evaluated as
delivery vehicles. Immunization studies in experimental rodent models for various
cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and
lung cancer as well as melanoma have been conducted with naturally occurring
oncolytic alphavirus strains such as M1 and Sindbis AR339. Moreover, animals were
vaccinated with engineered oncolytic replication-deficient and -competent Semliki
Forest virus, Sindbis virus and Venezuelan equine encephalitis virus vectors
expressing various antigens. Vaccinations elicited strong antibody responses and
resulted in tumor growth inhibition, tumor regression and even complete tumor
eradication. Vaccination also led to prolonged survival in several animal models.
Furthermore, preclinical evaluation demonstrated both prophylactic and
therapeutic efficacy of oncolytic alphavirus administration. Clinical trials in
humans have mainly been limited to safety studies so far.
PMID- 28417937
TI - Study on the Health Status and Health Service Utilization of the Elderly of a
Remote and Poor Village in a Mountainous Area in Jinzhai, Anhui.
AB - Background: Despite the rapid development of China's economy, a number of poor
areas in China continue to exist. The health status of the elderly in the poor
areas is a matter of concern. This study aims to explore the status of the
elderly in terms of their health status, health service needs, and utilization
among rural residents of a remote and poor village in a mountainous area in
Jinzhai, Anhui. Furthermore, this study aims to explore the differences between
the nation rural area average level and the remote and poor village in the
mountainous area in terms of health status and health service utilization.
Methods: Cluster sampling was used to obtain the sample. A total of 110 elderly
people were selected from the village, and face-to-face interviews were conducted
with questionnaires by trained investigators to collect data. Results: All items
except vision, language disability, and self-care disability were found to be
higher than the national average level. In terms of mental health, Zishu Village
has a ratio of 44.1% for the symptoms of anxiety and depression, which is higher
than the average for the national rural areas. The two-week prevalence rate,
prevalence of chronic diseases, and non-hospitalization rate of those who need
hospitalization (%) in Zishu Village was 62.7%, 88.2%, and 47.6% respectively,
which was higher than the rural values of the National Survey (2008). Most of the
outpatient visits were to the village clinics, while the hospitalizations were
mainly to county hospitals. The two-week visiting rate was 24.1%, which was lower
than 2008. The hospitalization rate in Zishu Village was 10.8%, which is similar
to the level of 2008. Conclusions: The health level and the utilization of health
services of the people in Zishu Village, Jinzhai, are generally lower than the
national average. Financial difficulties continue to remain the major factor
affecting the utilization of hospitalization services of this remote and poor
village in Jinzhai, Anhui.
PMID- 28417938
TI - Recent Advances in Cyanamide Chemistry: Synthesis and Applications.
AB - The application of alkyl and aryl substituted cyanamides in synthetic chemistry
has diversified multi-fold in recent years. In this review, we discuss recent
advances (since 2012) in the chemistry of cyanamides and detail their application
in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic
cyanide-transfer agents and their unique radical and coordination chemistry.
PMID- 28417939
TI - Soil Lead and Children's Blood Lead Disparities in Pre- and Post-Hurricane
Katrina New Orleans (USA).
AB - This study appraises New Orleans soil lead and children's lead exposure before
and ten years after Hurricane Katrina flooded the city. Introduction: Early
childhood exposure to lead is associated with lifelong and multiple health,
learning, and behavioral disorders. Lead exposure is an important factor
hindering the long-term resilience and sustainability of communities. Lead
exposure disproportionately affects low socioeconomic status of communities. No
safe lead exposure is known and the common intervention is not effective. An
essential responsibility of health practitioners is to develop an effective
primary intervention. Methods: Pre- and post-Hurricane soil lead and children's
blood lead data were matched by census tract communities. Soil lead and blood
lead data were described, mapped, blood lead graphed as a function of soil lead,
and Multi-Response Permutation Procedures statistics established disparities.
Results: Simultaneous decreases occurred in soil lead accompanied by an
especially large decline in children's blood lead 10 years after Hurricane
Katrina. Exposure disparities still exist between children living in the interior
and outer areas of the city. Conclusions: At the scale of a city, this study
demonstrates that decreasing soil lead effectively reduces children's blood lead.
Primary prevention of lead exposure can be accomplished by reducing soil lead in
the urban environment.
PMID- 28417940
TI - Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer
and Normal Cells, and Effects Cisplatin Cytotoxicity.
AB - Uncaria tomentosa is a woody vine with a long history of use in traditional
Peruvian medicine and nowadays supplements containing this vine as ingredient are
available. Immunomodulating, anti-inflammatory and anticancer properties of
Uncaria tomentosa have been suggested and attributed mainly to the presence of
tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of
different compounds occurring in extracts and modulation of redox processes may
significantly influence the anticancer activity of Uncaria tomentosa. The aim of
the present study was to investigate for the first time the cytotoxic effects of
the tetracyclic alkaloids free aqueous extract (decoction) of dried Uncaria
tomentosa leaf blades in normal and cancer cells, and to assess the effect of the
tested extract on cisplatin (CDDP) cytotoxicity. Tested Uncaria tomentosa extract
was not cytotoxic for NHDF cells, but demonstrated cytotoxic effect against HepG2
cells. The extract increased ROS production in HepG2 cells, which resulted in
decreased GSH level, leading to apoptosis of these cells through activation of
caspase-3 and caspase-7. A reduction of NF-kappaB active form was observed in
cancer cells. In normal cells the extract did not affect ROS production, GSH
level and NF-kappaB activity, and maintained cell viability. HepG2 cells
incubation with Uncaria tomentosa decoction and simultaneously with CDDP resulted
in an increase in CDPP cytotoxic activity against HepG2, while under the same
conditions Uncaria tomentosa prevents NHDF cell viability reduction due to CDDP.
The results indicate that Uncaria tomentosa leaves decoction modulates
differently cancer and normal cells oxidative metabolism and, enhanced
cytotoxicity of CDDP against cancer cells and at the same time increased normal
healthy cells resistance to cisplatin. Further studies are needed to confirm our
observations and to describe underlying molecular mechanism, and the potential
usefulness of Uncaria tomentosa decoction in adjuvant therapy for cancer.
PMID- 28417941
TI - Mapping Patterns and Trends in the Spatial Availability of Alcohol Using Low
Level Geographic Data: A Case Study in England 2003-2013.
AB - Much literature examines the relationship between the spatial availability of
alcohol and alcohol-related harm. This study aims to address an important gap in
this evidence by using detailed outlet data to examine recent temporal trends in
the sociodemographic distribution of spatial availability for different types of
alcohol outlet in England. Descriptive analysis of measures of alcohol outlet
density and proximity using extremely high resolution market research data
stratified by outlet type and quintiles of area-level deprivation from 2003,
2007, 2010 and 2013 was undertaken and hierarchical linear growth models fitted
to explore the significance of socioeconomic differences. We find that overall
availability of alcohol changed very little from 2003 to 2013 (density +1.6%),
but this conceals conflicting trends by outlet type and area-level deprivation.
Mean on-trade density has decreased substantially (-2.2 outlets within 1 km
(Inter-Quartile Range (IQR) -3-0), although access to restaurants has increased
(+1.0 outlets (IQR 0-1)), while off-trade access has risen substantially (+2.4
outlets (IQR 0-3)). Availability is highest in the most deprived areas (p <
0.0001) although these areas have also seen the greatest falls in on-trade outlet
availability (p < 0.0001). This study underlines the importance of using
detailed, low-level geographic data to understand patterns and trends in the
spatial availability of alcohol. There are significant variations in these trends
by outlet type and deprivation level which may have important implications for
health inequalities and public health policy.
PMID- 28417943
TI - LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in
Mistletoe Berry Extracts from Different Host Trees.
AB - A new, rapid, sensitive and selective liquid chromatography-electrospray
ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to
determine the content of flavonoid aglycones and phenolic acids in mistletoe
berries (Viscum album L.) harvested from six different Polish host trees.
Additionally, the total phenolic content (TPC) and total flavonoid content (TFC)
as well as an antioxidant and antiproliferative activity were evaluated for the
first time. The plant material was selectively extracted using ultrasound
assisted maceration with methanol/water (8:2) solution. The obtained TPC and TFC
results varied from 7.146 to 9.345 mg GA g-1 and from 1.888 to 2.888 mg Q g-1 of
dry extracts, respectively. The LC-ESI-MS/MS analysis demonstrated the highest
content of phenolic acids in mistletoe berries from Populus nigra 'Italica' L.
and flavonoid aglycones in mistletoe berries from Tilia cordata Mill. (354.45 ug
and 5.955 ug per g dry extract, respectively). The moderate antioxidant activity
of investigated extracts was obtained. The studies revealed that the examined
extracts decreased the proliferation of human colon adenocarcinoma cells line
LS180 in a dose-dependent manner without cytotoxicity in the human colon
epithelial cell line CCD 841 CoTr. Moreover, the obtained results suggest
considerable impact of polyphenols on the anticancer activity of these extracts.
PMID- 28417942
TI - Protein Discovery: Combined Transcriptomic and Proteomic Analyses of Venom from
the Endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae).
AB - Many species of endoparasitoid wasps provide biological control services in
agroecosystems. Although there is a great deal of information on the ecology and
physiology of host/parasitoid interactions, relatively little is known about the
protein composition of venom and how specific venom proteins influence
physiological systems within host insects. This is a crucial gap in our knowledge
because venom proteins act in modulating host physiology in ways that favor
parasitoid development. Here, we identified 37 possible venom proteins from the
polydnavirus-carrying endoparasitoid Cotesia chilonis by combining transcriptomic
and proteomic analyses. The most abundant proteins were hydrolases, such as
proteases, peptidases, esterases, glycosyl hydrolase, and endonucleases. Some
components are classical parasitoid venom proteins with known functions,
including extracellular superoxide dismutase 3, serine protease inhibitor and
calreticulin. The venom contains novel proteins, not recorded from any other
parasitoid species, including tolloid-like proteins, chitooligosaccharidolytic
beta-N-acetylglucosaminidase, FK506-binding protein 14, corticotropin-releasing
factor-binding protein and vascular endothelial growth factor receptor 2. These
new data generate hypotheses and provide a platform for functional analysis of
venom components.
PMID- 28417944
TI - Variable Admittance Control Based on Fuzzy Reinforcement Learning for Minimally
Invasive Surgery Manipulator.
AB - In order to get natural and intuitive physical interaction in the pose adjustment
of the minimally invasive surgery manipulator, a hybrid variable admittance model
based on Fuzzy Sarsa(lambda)-learning is proposed in this paper. The proposed
model provides continuous variable virtual damping to the admittance controller
to respond to human intentions, and it effectively enhances the comfort level
during the task execution by modifying the generated virtual damping dynamically.
A fuzzy partition defined over the state space is used to capture the
characteristics of the operator in physical human-robot interaction. For the
purpose of maximizing the performance index in the long run, according to the
identification of the current state input, the virtual damping compensations are
determined by a trained strategy which can be learned through the experience
generated from interaction with humans, and the influence caused by humans and
the changing dynamics in the robot are also considered in the learning process.
To evaluate the performance of the proposed model, some comparative experiments
in joint space are conducted on our experimental minimally invasive surgical
manipulator.
PMID- 28417945
TI - One-Pot Phosphate-Mediated Synthesis of Novel 1,3,5-Trisubstituted Pyridinium
Salts: A New Family of S. aureus Inhibitors.
AB - Polysubstituted pyridinium salts are valuable pharmacophores found in many
biologically active molecules. Their synthesis typically involves the use of
multistep procedures or harsh reaction conditions. Here, we report water-based
phosphate mediated reaction conditions that promote the condensation of
arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction,
carried out at pH 6, provides conditions suitable for the use of less stable
aldehydes and amines in this Chichibabin pyridine condensation. The evaluation of
selected 1,3,5-trisubstituted pyridinium salts highlighted that they can inhibit
the growth of S. aureus in the low MUg/mL range. The synthetic accessibility of
these compounds and preliminary growth inhibition data may pave the way towards
the discovery of new anti-bacterials based on the 1,3,5-trisubstituted pyridinium
scaffold.
PMID- 28417946
TI - Essential Oils of Hyptis pectinata Chemotypes: Isolation, Binary Mixtures and
Acute Toxicity on Leaf-Cutting Ants.
AB - Leaf-cutting ants are pests of great economic importance due to the damage they
cause to agricultural and forest crops. The use of organosynthetic insecticides
is the main form of control of these insects. In order to develop safer
technology, the objective of this work was to evaluate the formicidal activity of
the essential oils of two Hyptis pectinata genotypes (chemotypes) and their major
compounds on the leaf-cutting ants Acromyrmex balzani Emery and Atta sexdens
rubropilosa Forel. Bioassays of exposure pathways (contact and fumigation) and
binary mixtures of the major compounds were performed. The major compounds
identified in the essential oils of H. pectinata were beta-caryophyllene,
caryophyllene oxide and calamusenone. The essential oils of H. pectinata were
toxic to the ants in both exposure pathways. Essential oils were more toxic than
their major compounds alone. The chemotype calamusenone was more toxic to A.
balzani in both exposure pathways. A. sexdens rubropilosa was more susceptible to
the essential oil of the chemotype beta-caryophyllene in both exposure pathways.
In general, the binary mixtures of the major compounds resulted in additive
effect of toxicity. The essential oils of H. pectinata is a raw material of great
potential for the development of new insecticides.
PMID- 28417947
TI - Pro-Angiogenic Effects of Low Dose Ethoxidine in a Murine Model of Ischemic
Hindlimb: Correlation between Ethoxidine Levels and Increased Activation of the
Nitric Oxide Pathway.
AB - Ethoxidine, a benzo[c]phenanthridine derivative, has been identified as a potent
inhibitor of topoisomerase I in cancer cell lines. Our group has reported
paradoxical properties of ethoxidine in cellular processes leading to
angiogenesis on endothelial cells. Because low concentration ethoxidine is able
to favor angiogenesis, the present study aimed to investigate the ability of 10-9
M ethoxidine to modulate neovascularization in a model of mouse hindlimb
ischemia. After inducing unilateral hindlimb ischemia, mice were treated for 21
days with glucose 5% or with ethoxidine, to reach plasma concentrations
equivalent to 10-9 M. Laser Doppler analysis showed that recovery of blood flow
was 1.5 fold higher in ethoxidine-treated mice in comparison with control mice.
Furthermore, CD31 staining and angiographic studies confirmed an increase of
vascular density in ethoxidine-treated mice. This ethoxidine-induced recovery was
associated with an increase of NO production through an enhancement of eNOS
phosphorylation on its activator site in skeletal muscle from ischemic hindlimb.
Moreover, real-time RT-PCR and western blots have highlighted that ethoxidine has
pro-angiogenic properties by inducing a significant enhancement in vegf
transcripts and VEGF expression, respectively. These findings suggest that
ethoxidine could contribute to favor neovascularization after an ischemic injury
by promoting the NO pathway and VEGF expression.
PMID- 28417949
TI - Implementation and Analysis of Real-Time Streaming Protocols.
AB - Communication media have become the primary way of interaction thanks to the
discovery and innovation of many new technologies. One of the most widely used
communication systems today is video streaming, which is constantly evolving.
Such communications are a good alternative to face-to-face meetings, and are
therefore very useful for coping with many problems caused by distance. However,
they suffer from different issues such as bandwidth limitation, network
congestion, energy efficiency, cost, reliability and connectivity. Hence, the
quality of service and the quality of experience are considered the two most
important issues for this type of communication. This work presents a complete
comparative study of two of the most used protocols of video streaming, Real Time
Streaming Protocol (RTSP) and the Web Real-Time Communication (WebRTC). In
addition, this paper proposes two new mobile applications that implement those
protocols in Android whose objective is to know how they are influenced by the
aspects that most affect the streaming quality of service, which are the
connection establishment time and the stream reception time. The new video
streaming applications are also compared with the most popular video streaming
applications for Android, and the experimental results of the analysis show that
the developed WebRTC implementation improves the performance of the most popular
video streaming applications with respect to the stream packet delay.
PMID- 28417950
TI - Differential Gender Effects in the Relationship between Perceived Immune
Functioning and Autistic Traits.
AB - Altered immune functioning has been demonstrated in individuals with autism
spectrum disorder (ASD). The current study explores the relationship between
perceived immune functioning and experiencing ASD traits in healthy young adults.
N = 410 students from Utrecht University completed a survey on immune functioning
and autistic traits. In addition to a 1-item perceived immune functioning rating,
the Immune Function Questionnaire (IFQ) was completed to assess perceived immune
functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) was
completed to examine variation in autistic traits, including the domains "social
insights and behavior", "difficulties with change", "communication", "phantasy
and imagination", and "detail orientation". The 1-item perceived immune
functioning score did not significantly correlate with the total AQ score.
However, a significant negative correlation was found between perceived immune
functioning and the AQ subscale "difficulties with change" (r = -0.119, p =
0.019). In women, 1-item perceived immune functioning correlated significantly
with the AQ subscales "difficulties with change" (r = -0.149, p = 0.029) and
"communication" (r = -0.145, p = 0.032). In men, none of the AQ subscales
significantly correlated with 1-item perceived immune functioning. In conclusion,
a modest relationship between perceived immune functioning and several autistic
traits was found.
PMID- 28417951
TI - Association of Motorcycle Use with Risk of Overweight in Taiwanese Urban Adults.
AB - Sedentary transport is known to adversely affect health. Few studies have focused
on motorcycle use. This study examines the association of motorcycle use with
overweight in urban adults in Taiwan. Cross-sectional data from 1069 Taiwanese
adults aged 20-64 years in three urban cities were collected in 2015. Data on
self-reported body mass index, time spent in motorcycle use, lifestyle behavioral
factors, and sociodemographic variables were obtained. Unadjusted and adjusted
logistic regression models were applied. In Model 1, adults who spent more time
using a motorcycle (third quartile, odds ratio (OR) = 1.17; fourth quartile, OR =
1.60) were more likely to be overweight compared with the first quartile. In
Model 2, after adjusting for the covariates, only the fourth quartile of
motorcycle use (OR = 1.50) was associated with a higher risk of overweight.
Higher time spent in motorcycle use is related to higher risk of being
overweight, even after adjustment for potential demographic and behavioral
confounders. Intervention and behavioral change strategies targeting motorcycle
use should be considered.
PMID- 28417948
TI - ErbB Family Signalling: A Paradigm for Oncogene Addiction and Personalized
Oncology.
AB - ErbB family members represent important biomarkers and drug targets for modern
precision therapy. They have gained considerable importance as paradigms for
oncoprotein addiction and personalized medicine. This review summarizes the
current understanding of ErbB proteins in cell signalling and cancer and
describes the molecular rationale of prominent cases of ErbB oncoprotein
addiction in different cancer types. In addition, we have highlighted
experimental technologies for the development of innovative cancer cell models
that accurately predicted clinical ErbB drug efficacies. In the future, such
cancer models might facilitate the identification and validation of
physiologically relevant novel forms of oncoprotein and non-oncoprotein addiction
or synthetic lethality. The identification of genotype-drug response
relationships will further advance personalized oncology and improve drug
efficacy in the clinic. Finally, we review the most important drugs targeting
ErbB family members that are under investigation in clinical trials or that made
their way already into clinical routine. Taken together, the functional
characterization of ErbB oncoproteins have significantly increased our knowledge
on predictive biomarkers, oncoprotein addiction and patient stratification and
treatment.
PMID- 28417952
TI - Investigating the molecular mechanism of positive and negative allosteric
modulators in the calcium-sensing receptor dimer.
AB - Allosteric modulators that are targeting the calcium-sensing receptor (CaSR) hold
great therapeutic potential, and elucidating the molecular basis for modulation
would thus benefit the development of novel therapeutics. In the present study,
we aimed at investigating the mechanism of allosteric modulation in CaSR by
testing dimers carrying mutations in the allosteric site of one or both of the
subunits. To ensure measurements on a well-defined dimer composition, we applied
a trans-activation system in which only the specific heterodimer of two loss-of
function mutants responded to agonist. Although one of these mutants was
potentiated by a positive allosteric modulator, we showed that receptor activity
was further potentiated in a trans-activation heterodimer containing a single
allosteric site, however only when the allosteric site was located in the subunit
responsible for G protein coupling. On the contrary, preventing activation in
both subunits was necessary for obtaining full inhibition by a negative
allosteric modulator. These findings correlate with the proposed activation
mechanism of the metabotropic glutamate receptors (mGluRs), in which only a
single transmembrane domain is activated at a time. CaSR and mGluRs belong to the
class C G protein-coupled receptors, and our findings thus suggest that the
activation mechanism is common to this subfamily.
PMID- 28417954
TI - Oxygen Vacancy-Tuned Physical Properties in Perovskite Thin Films with Multiple B
site Valance States.
AB - Controlling oxygen content in perovskite oxides with ABO3 structure is one of
most critical steps for tuning their functionality. Notably, there have been
tremendous efforts to understand the effect of changes in oxygen content on the
properties of perovskite thin films that are not composed of cations with
multiple valance states. Here, we study the effect of oxygen vacancies on
structural and electrical properties in epitaxial thin films of SrFeO3-delta
(SFO), where SFO is a compound with multiple valance states at the B site.
Various annealing treatments are used to produce different oxygen contents in the
films, which has resulted in significant structural changes in the fully strained
SFO films. The out-of-plane lattice parameter and tetragonality increase with
decreasing oxygen concentration, indicating the crystal structure is closely
related to the oxygen content. Importantly, variation of the oxygen content in
the films significantly affects the dielectric properties, leakage conduction
mechanisms, and the resistive hysteresis of the materials. These results
establish the relationship between oxygen content and structural and functional
properties for a range of multivalent transition metal oxides.
PMID- 28417953
TI - Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model
of Dopamine Transporter Deficiency Syndrome.
AB - Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive
disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene,
leading to severe neurological disabilities in children and adults. DAT-Knockout
(DAT-KO) mouse is currently the best animal model for this syndrome, displaying
functional hyperdopaminergia and neurodegenerative phenotype leading to premature
death in ~36% of the population. We used DAT-KO mouse as model for DTDS to
explore the potential utility of a novel combinatorial adeno-associated viral
(AAV) gene therapy by expressing DAT selectively in DA neurons and terminals,
resulting in the rescue of aberrant striatal DA dynamics, reversal of
characteristic phenotypic and behavioral abnormalities, and prevention of
premature death. These data indicate the efficacy of a new combinatorial gene
therapy aimed at rescuing DA function and related phenotype in a mouse model that
best approximates DAT deficiency found in DTDS.
PMID- 28417955
TI - Zero birefringence films of pullulan ester derivatives.
AB - High-performance films with almost zero-birefringence and zero-wavelength
dispersion were succeeded to prepare from pullulan esters derivatives (PLEs)
without any additives. Optical transmittance analysis, birefringence measurement
of PLE cast film and hot stretched films, and infrared dichroism analysis were
conducted to characterize optical properties of PLE films comparing with
cellulose triacetate which is commercially used as low-birefringence in optical
devices. The aims of this study, characterization of optical properties of
pullulan esters, can develop a deep understanding of the fundamental knowing and
applicability of polysaccharides. Accordingly, authors believe this paper will
open the gate for researches in the application of polysaccharides.
PMID- 28417956
TI - Establishment and characterization of an orthotopic patient-derived Group 3
medulloblastoma model for preclinical drug evaluation.
AB - Medulloblastomas comprise a heterogeneous group of tumours and can be subdivided
into four molecular subgroups (WNT, SHH, Group 3 and Group 4) with distinct
prognosis, biological behaviour and implications for targeted therapies. Few
experimental models exist of the aggressive and poorly characterized Group 3
tumours. In order to establish a reproducible transplantable Group 3
medulloblastoma model for preclinical therapeutic studies, we acquired a patient
derived tumour sphere culture and inoculated low-passage spheres into the
cerebellums of NOD-scid mice. Mice developed symptoms of brain tumours with a
latency of 17-18 weeks. Neurosphere cultures were re-established and serially
transplanted for 3 generations, with a negative correlation between tumour
latency and numbers of injected cells. Xenografts replicated the phenotype of the
primary tumour, including high degree of clustering in DNA methylation analysis,
high proliferation, expression of tumour markers, MYC amplification and elevated
MYC expression, and sensitivity to the MYC inhibitor JQ1. Xenografts maintained
maintained expression of tumour-derived VEGFA and stromal-derived COX-2. VEGFA,
COX-2 and c-Myc are highly expressed in Group 3 compared to other medulloblastoma
subgroups, suggesting that these molecules are relevant therapeutic targets in
Group 3 medulloblastoma.
PMID- 28417957
TI - Attractive force-driven superhardening of graphene membranes as a pin-point
breaking of continuum mechanics.
AB - Bending at the nanometre scale can substantially modify the mechanical, chemical
and electronic properties of graphene membranes. The subsequent response of
chemical bonds leads to deviations from plate idealisation in continuum
mechanics. However, those phenomena have thus far been investigated exclusively
by measuring the electronic properties of graphene deformed by compressing and
stretching with local-probe techniques. Here, we report that the interatomic
attractive forces applied on the convexly-curved graphene by the probe tip give
rise to a pin-point breaking of the plate idealisation in the continuum
mechanics, facilitating atomically-localised enhancements in its chemical
reactivity and mechanical strength. Thorough characterisations were conducted by
atomic force microscopy and force field spectroscopy on hollow nanotubes, rolled
up graphene, with different diameters. Their topmost parts supplied well-defined
curvatures of the convex graphene. We found that a significant enhancement in the
out-of-plane Young's modulus from 13 to 163 GPa, "superhardening", was realised
with the nonlinear transition of bond configurations. Our findings provide a
fundamental understanding of the relationships between the structure of atomistic
membranes and the dynamic behaviour of approaching exterior atoms or molecules
and their subsequent interplay with chemical and mechanical properties. Thus,
these results encourage the application of such membranes in functionally
controllable materials or devices.
PMID- 28417958
TI - Widespread patterns of sexually dimorphic gene expression in an avian
hypothalamic-pituitary-gonadal (HPG) axis.
AB - The hypothalamic-pituitary-gonadal (HPG) axis is a key biological system required
for reproduction and associated sexual behaviors to occur. In the avian
reproductive model of the rock dove (Columba livia), we characterized the
transcript community of each tissue of the HPG axis in both sexes, thereby
significantly expanding our mechanistic insight into HPG activity. We report
greater sex-biased differential expression in the pituitary as compared to the
hypothalamus, with multiple genes more highly expressed in the male pituitary
being related to secretory function, and multiple genes more highly expressed in
the female pituitary being related to reproduction, growth, and development. We
report tissue-specific and sex-biased expression in genes commonly investigated
when studying reproduction, highlighting the need for sex parity in future
studies. In addition, we uncover new targets of investigation in both sexes,
which could potentially change our understanding of HPG function.
PMID- 28417959
TI - Genome sequence of Plasmopara viticola and insight into the pathogenic mechanism.
AB - Plasmopara viticola causes downy mildew disease of grapevine which is one of the
most devastating diseases of viticulture worldwide. Here we report a 101.3 Mb
whole genome sequence of P. viticola isolate 'JL-7-2' obtained by a combination
of Illumina and PacBio sequencing technologies. The P. viticola genome contains
17,014 putative protein-coding genes and has ~26% repetitive sequences. A total
of 1,301 putative secreted proteins, including 100 putative RXLR effectors and 90
CRN effectors were identified in this genome. In the secretome, 261 potential
pathogenicity genes and 95 carbohydrate-active enzymes were predicted.
Transcriptional analysis revealed that most of the RXLR effectors, pathogenicity
genes and carbohydrate-active enzymes were significantly up-regulated during
infection. Comparative genomic analysis revealed that P. viticola evolved
independently from the Arabidopsis downy mildew pathogen Hyaloperonospora
arabidopsidis. The availability of the P. viticola genome provides a valuable
resource not only for comparative genomic analysis and evolutionary studies among
oomycetes, but also enhance our knowledge on the mechanism of interactions
between this biotrophic pathogen and its host.
PMID- 28417960
TI - Normally lethal amino acid substitutions suppress an ultramutator DNA Polymerase
delta variant.
AB - In yeast, the pol3-01,L612M double mutant allele, which causes defects in DNA
polymerase delta (Pol delta) proofreading (pol3-01) and nucleotide selectivity
(pol3-L612M), confers an "ultramutator" phenotype that rapidly drives extinction
of haploid and diploid MMR-proficient cells. Here, we investigate antimutator
mutations that encode amino acid substitutions in Pol delta that suppress this
lethal phenotype. We find that most of the antimutator mutations individually
suppress the pol3-01 and pol3-L612M mutator phenotypes. The locations of many of
the amino acid substitutions in Pol delta resemble those of previously identified
antimutator substitutions; however, two novel mutations encode substitutions
(R674G and Q697R) of amino acids in the fingers domain that coordinate the
incoming dNTP. These mutations are lethal without pol3-L612M and markedly change
the mutation spectra produced by the pol3-01,L612M mutator allele, suggesting
that they alter nucleotide selection to offset the pol3-L612M mutator phenotype.
Consistent with this hypothesis, mutations and drug treatments that perturb dNTP
pool levels disproportionately influence the viability of pol3-L612M,R674G and
pol3-L612M,Q697R cells. Taken together, our findings suggest that mutation rate
can evolve through genetic changes that alter the balance of dNTP binding and
dissociation from DNA polymerases.
PMID- 28417961
TI - High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and
mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage.
AB - Subarachnoid haemorrhage (SAH) is a fatal neurovascular disease following
cerebral aneurysm rupture with high morbidity and mortality rates. Long non
coding RNAs (lncRNAs) are a type of mammalian genome transcript, are abundantly
expressed in the brain and are involved in many nervous system diseases. However,
little is currently known regarding the influence of lncRNAs in early brain
injury (EBI) after SAH. This study analysed the expression profiles of lncRNAs
and mRNAs in SAH brain tissues of mice using high-throughput sequencing. The
results showed a remarkable difference in lncRNA and mRNA transcripts between SAH
and control brains. Approximately 617 lncRNA transcripts and 441 mRNA transcripts
were aberrantly expressed at 24 hours after SAH. Gene ontology (GO) enrichment
and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the
differentially expressed mRNAs were mostly involved in inflammation. Based on the
lncRNA/mRNA co-expression network, knockdown of fantom3_F730004F19 reduced the
mRNA and protein levels of CD14 and toll-like receptor 4 (TLR4) and attenuated
inflammation in BV-2 microglia cells. These results indicate that lncRNA
fantom3_F730004F19 may be associated with microglia induced inflammation via the
TLR signaling pathway in EBI following SAH. LncRNA represent a potential
therapeutic target for the prognosis, diagnosis, and treatment of SAH.
PMID- 28417962
TI - Multiple p-n junction subwavelength gratings for transmission-mode electro-optic
modulators.
AB - We propose a free-space electro-optic transmission modulator based on multiple p
n-junction semiconductor subwavelength gratings. The proposed device operates
with a high-Q guided-mode resonance undergoing electro-optic resonance shift due
to direct electrical control. Using rigorous electrical and optical modeling
methods, we theoretically demonstrate a modulation depth of 84%, on-state
efficiency 85%, and on-off extinction ratio of 19 dB at 1,550 nm wavelength under
electrical control signals within a favorably low bias voltage range from -4 V to
+1 V. This functionality operates in the transmission mode and sustainable in the
high-speed operation regime up to a 10-GHz-scale modulation bandwidth in
principle. The theoretical performance prediction is remarkably advantageous over
plasmonic tunable metasurfaces in the power-efficiency and absolute modulation
depth aspects. Therefore, further experimental study is of great interest for
creating practical-level metasurface components in various application areas.
PMID- 28417963
TI - Loop diuretics affect skeletal myoblast differentiation and exercise-induced
muscle hypertrophy.
AB - Muscle wasting or sarcopenia contributes to morbidity and mortality in patients
with cancer, renal failure, or heart failure, and in elderly individuals. Na+-K+
2Cl- cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle,
where it contributes to the generation of membrane ion currents and potential.
However, the physiologic function of NKCC1 in myogenesis is unclear. We
investigated this issue using the NKCC1 inhibitors bumetanide and furosemide,
which are commonly used loop diuretics. NKCC1 protein levels increased during
C2C12 murine skeletal myoblast differentiation, similarly to those of the
myogenic markers myogenin and myosin heavy chain (MHC). NKCC1 inhibitors markedly
suppressed myoblast fusion into myotubes and the expression of myogenin and MHC.
Furthermore, phosphorylated and total NKCC1 levels were elevated in mouse
skeletal muscles after 6 weeks' voluntary wheel running. Immunofluorescence
analyses of myofiber cross-sections revealed more large myofibers after exercise,
but this was impaired by daily intraperitoneal bumetanide injections (0.2 or 10
mg/kg/day). NKCC1 plays an essential role in myogenesis and exercise-induced
skeletal muscle hypertrophy, and sarcopenia in patients with renal or heart
failure may be attributable to treatment with loop diuretics.
PMID- 28417964
TI - Light-Patterned Current Generation in a Droplet Bilayer Array.
AB - We have created a 4 * 4 droplet bilayer array comprising light-activatable
aqueous droplet bio-pixels. Aqueous droplets containing bacteriorhodopsin (bR), a
light-driven proton pump, were arranged on a common hydrogel surface in lipid
containing oil. A separate lipid bilayer formed at the interface between each
droplet and the hydrogel; each bilayer then incorporated bR. Electrodes in each
droplet simultaneously measured the light-driven proton-pumping activities of
each bio-pixel. The 4 * 4 array derived by this bottom-up synthetic biology
approach can detect grey-scale images and patterns of light moving across the
device, which are transduced as electrical current generated in each bio-pixel.
We propose that synthetic biological light-activatable arrays, produced with soft
materials, might be interfaced with living tissues to stimulate neuronal
pathways.
PMID- 28417965
TI - Distinct subtypes of Alzheimer's disease based on patterns of brain atrophy:
longitudinal trajectories and clinical applications.
AB - Atrophy patterns on MRI can reliably predict three neuropathological subtypes of
Alzheimer's disease (AD): typical, limbic-predominant, or hippocampal-sparing. A
method to enable their investigation in the clinical routine is still lacking. We
aimed to (1) validate the combined use of visual rating scales for identification
of AD subtypes; (2) characterise these subtypes at baseline and over two years;
and (3) investigate how atrophy patterns and non-memory cognitive domains
contribute to memory impairment. AD patients were classified as either typical AD
(n = 100), limbic-predominant (n = 33), or hippocampal-sparing (n = 35) by using
the Scheltens' scale for medial temporal lobe atrophy (MTA), the Koedam's scale
for posterior atrophy (PA), and the Pasquier's global cortical atrophy scale for
frontal atrophy (GCA-F). A fourth group with no atrophy was also identified (n =
30). 230 healthy controls were also included. There was great overlap among
subtypes in demographic, clinical, and cognitive variables. Memory performance
was more dependent on non-memory cognitive functions in hippocampal-sparing and
the no atrophy group. Hippocampal-sparing and the no atrophy group showed less
aggressive disease progression. Visual rating scales can be used to identify
distinct AD subtypes. Recognizing AD heterogeneity is important and visual rating
scales may facilitate investigation of AD heterogeneity in clinical routine.
PMID- 28417966
TI - The ecdysis triggering hormone system is essential for successful moulting of a
major hemimetabolous pest insect, Schistocerca gregaria.
AB - Insects are enclosed in a rigid exoskeleton, providing protection from
desiccation and mechanical injury. To allow growth, this armour needs to be
replaced regularly in a process called moulting. Moulting entails the production
of a new exoskeleton and shedding of the old one and is induced by a pulse in
ecdysteroids, which activates a peptide-mediated signalling cascade. In
Holometabola, ecdysis triggering hormone (ETH) is the key factor in this cascade.
Very little functional information is available in Hemimetabola, which display a
different kind of development characterized by gradual changes. This paper
reports on the identification of the ETH precursor and the pharmacological and
functional characterisation of the ETH receptor in a hemimetabolous pest species,
the desert locust, Schistocerca gregaria. Activation of SchgrETHR by SchgrETH
results in an increase of both Ca2+ and cyclic AMP, suggesting that SchgrETHR
displays dual coupling properties in an in vitro cell-based assay. Using qRT-PCR,
an in-depth profiling study of SchgrETH and SchgrETHR transcripts was performed.
Silencing of SchgrETH and SchgrETHR resulted in lethality at the expected time of
ecdysis, thereby showing their crucial role in moulting.
PMID- 28417967
TI - Nomograms for predicting the prognostic value of serological tumor biomarkers in
colorectal cancer patients after radical resection.
AB - A wide range of serum tumor biomarkers, including CA19-9, CA242, CA72-4, CA50,
and CA125, has been studied in association with colorectal cancer (CRC). However,
few previous studies have comprehensively considered the above tumor biomarkers
to assess their clinical significance in predicting prognosis. Data from Fudan
University Shanghai Cancer Center (FUSCC) between January 1, 2007 and December
30, 2012 was retrospectively analyzed. Univariate and multivariate analyses were
performed to assess the association between prognostic factors and survival
outcomes. Nomograms were established based on multivariate Cox regression model
analysis for overall survival (OS) and disease free survival (DFS), and c-indexes
were 0.772 (95% CI: 0.724-0.820) and 0.715 (95% CI: 0.678-0.752), respectively.
Subgroup analyses according to CEA status (high/normal) suggested that CA724 was
the only independent prognostic factor for OS (P = 0.001) and DFS (P < 0.001) in
the CEA-high group, while, in the CEA-normal group, the only independent
prognostic factor for OS (P = 0.031) and DFS (P = 0.043) was CA50. CA50 and CA724
could supplement CEA in monitoring recurrence and metastasis. Accordingly,
nomograms based on CEA, CA50, CA724 and other clinical-pathological factors could
improve prognosis prediction for colorectal cancer patients.
PMID- 28417968
TI - Rational development of a protective P. vivax vaccine evaluated with transgenic
rodent parasite challenge models.
AB - Development of a protective and broadly-acting vaccine against the most widely
distributed human malaria parasite, Plasmodium vivax, will be a major step
towards malaria elimination. However, a P. vivax vaccine has remained elusive by
the scarcity of pre-clinical models to test protective efficacy and support
further clinical trials. In this study, we report the development of a highly
protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21,
able to provide 100% sterile protection against a stringent sporozoite challenge
in rodent models to malaria, where IgG2a antibodies were associated with
protection in absence of detectable PvCSP-specific T cell responses.
Additionally, we generated two novel transgenic rodent P. berghei parasite lines,
where the P. berghei csp gene coding sequence has been replaced with either full
length P. vivax VK210 or the allelic VK247 csp that additionally express GFP
Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63
and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit
high level cross-protection against parasites expressing either CSP allele, which
provide accessible and affordable models suitable to support the development of
P. vivax vaccines candidates. Rv21 is progressing to GMP production and has
entered a path towards clinical evaluation.
PMID- 28417969
TI - Massive introgression drives species radiation at the range limit of Anopheles
gambiae.
AB - Impacts of introgressive hybridisation may range from genomic erosion and species
collapse to rapid adaptation and speciation but opportunities to study these
dynamics are rare. We investigated the extent, causes and consequences of a
hybrid zone between Anopheles coluzzii and Anopheles gambiae in Guinea-Bissau,
where high hybridisation rates appear to be stable at least since the 1990s.
Anopheles gambiae was genetically partitioned into inland and coastal
subpopulations, separated by a central region dominated by A. coluzzii.
Surprisingly, whole genome sequencing revealed that the coastal region harbours a
hybrid form characterised by an A. gambiae-like sex chromosome and massive
introgression of A. coluzzii autosomal alleles. Local selection on chromosomal
inversions may play a role in this process, suggesting potential for
spatiotemporal stability of the coastal hybrid form and providing resilience
against introgression of medically-important loci and traits, found to be more
prevalent in inland A. gambiae.
PMID- 28417970
TI - Inorganic carbon physiology underpins macroalgal responses to elevated CO2.
AB - Beneficial effects of CO2 on photosynthetic organisms will be a key driver of
ecosystem change under ocean acidification. Predicting the responses of
macroalgal species to ocean acidification is complex, but we demonstrate that the
response of assemblages to elevated CO2 are correlated with inorganic carbon
physiology. We assessed abundance patterns and a proxy for CO2:HCO3- use
(delta13C values) of macroalgae along a gradient of CO2 at a volcanic seep, and
examined how shifts in species abundance at other Mediterranean seeps are related
to macroalgal inorganic carbon physiology. Five macroalgal species capable of
using both HCO3- and CO2 had greater CO2 use as concentrations increased. These
species (and one unable to use HCO3-) increased in abundance with elevated CO2
whereas obligate calcifying species, and non-calcareous macroalgae whose CO2 use
did not increase consistently with concentration, declined in abundance.
Physiological groupings provide a mechanistic understanding that will aid us in
determining which species will benefit from ocean acidification and why.
PMID- 28417971
TI - Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based
morphometry study.
AB - Previous functional neuroimaging studies have identified multiple brain areas
associated with distinct aspects of car driving in simulated traffic
environments. Few studies, however, have examined brain morphology associated
with everyday car-driving experience in real traffic. Thus, the aim of the
current study was to identify gray matter volume differences between drivers and
non-drivers. We collected T1-weighted structural brain images from 73 healthy
young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel
based morphometry analysis to examine between-group differences in regional gray
matter volume. Compared with non-drivers, drivers showed significantly greater
gray matter volume in the left cerebellar hemisphere, which has been associated
with cognitive rather than motor functioning. In contrast, we found no brain
areas with significantly greater gray matter volume in non-drivers compared with
drivers. Our findings indicate that experience with everyday car driving in real
traffic is associated with greater gray matter volume in the left cerebellar
hemisphere. This brain area may be involved in abilities that are critical for
driving a car, but are not commonly or frequently used during other daily
activities.
PMID- 28417972
TI - The pretreatment lymphocyte to monocyte ratio predicts clinical outcome for
patients with hepatocellular carcinoma: A meta-analysis.
AB - The lymphocyte-to-monocyte ratio (LMR) has been reported to predict clinical
outcomes in multiple malignancies. The aim of this study was to assess the
prognostic role of pretreatment LMR in hepatocellular carcinoma (HCC). A total of
seven studies comprising 2,738 patients were included in the meta-analysis.
Pooled results showed that elevated LMR was significantly associated with
increased overall survival (OS) (HR: 0.31, 95% CI: 0.20-0.47, p < 0.001), disease
free survival (DFS)/recurrence-free survival (RFS) (HR: 0.57, 95% CI: 0.49-0.67,
p < 0.001). The favorable prognostic impact of high LMR on OS was observed in all
subgroup with different sample size, type of publication, NOS score, and the cut
off value of LMR. In addition, low LMR was significantly correlated with TNM
stage and BCLC stage. We therefore conclude that elevated pretreatment LMR could
be a favorable prognostic factor for clinical outcomes in patients with HCC.
PMID- 28417973
TI - Excitability in the p53 network mediates robust signaling with tunable activation
thresholds in single cells.
AB - Cellular signaling systems precisely transmit information in the presence of
molecular noise while retaining flexibility to accommodate the needs of
individual cells. To understand design principles underlying such versatile
signaling, we analyzed the response of the tumor suppressor p53 to varying levels
of DNA damage in hundreds of individual cells and observed a switch between
distinct signaling modes characterized by isolated pulses and sustained
oscillations of p53 accumulation. Guided by dynamic systems theory we show that
this requires an excitable network structure comprising positive feedback and
provide experimental evidence for its molecular identity. The resulting data
driven model reproduced all features of measured signaling responses and is
sufficient to explain their heterogeneity in individual cells. We present
evidence that heterogeneity in the levels of the feedback regulator Wip1 sets
cell-specific thresholds for p53 activation, providing means to modulate its
response through interacting signaling pathways. Our results demonstrate how
excitable signaling networks can provide high specificity, sensitivity and
robustness while retaining unique possibilities to adjust their function to the
physiology of individual cells.
PMID- 28417974
TI - The E. coli molecular phenotype under different growth conditions.
AB - Modern systems biology requires extensive, carefully curated measurements of
cellular components in response to different environmental conditions. While high
throughput methods have made transcriptomics and proteomics datasets widely
accessible and relatively economical to generate, systematic measurements of both
mRNA and protein abundances under a wide range of different conditions are still
relatively rare. Here we present a detailed, genome-wide transcriptomics and
proteomics dataset of E. coli grown under 34 different conditions. Additionally,
we provide measurements of doubling times and in-vivo metabolic fluxes through
the central carbon metabolism. We manipulate concentrations of sodium and
magnesium in the growth media, and we consider four different carbon sources
glucose, gluconate, lactate, and glycerol. Moreover, samples are taken both in
exponential and stationary phase, and we include two extensive time-courses, with
multiple samples taken between 3 hours and 2 weeks. We find that exponential
phase samples systematically differ from stationary-phase samples, in particular
at the level of mRNA. Regulatory responses to different carbon sources or salt
stresses are more moderate, but we find numerous differentially expressed genes
for growth on gluconate and under salt and magnesium stress. Our data set
provides a rich resource for future computational modeling of E. coli gene
regulation, transcription, and translation.
PMID- 28417975
TI - Exciton emission of quasi-2D InGaN in GaN matrix grown by molecular beam epitaxy.
AB - We investigate the emission from confined excitons in the structure of a single
monolayer-thick quasi-two-dimensional (quasi-2D) InxGa1-xN layer inserted in GaN
matrix. This quasi-2D InGaN layer was successfully achieved by molecular beam
epitaxy (MBE), and an excellent in-plane uniformity in this layer was confirmed
by cathodoluminescence mapping study. The carrier dynamics have also been
investigated by time-resolved and excitation-power-dependent photoluminescence,
proving that the recombination occurs via confined excitons within the ultrathin
quasi-2D InGaN layer even at high temperature up to ~220 K due to the enhanced
exciton binding energy. This work indicates that such structure affords an
interesting opportunity for developing high-performance photonic devices.
PMID- 28417977
TI - Multicolour nanoscopy of fixed and living cells with a single STED beam and
hyperspectral detection.
AB - The extension of fluorescence nanoscopy to larger numbers of molecular species
concurrently visualized by distinct markers is of great importance for advanced
biological applications. To date, up to four markers had been distinguished in
STED experiments featuring comparatively elaborate imaging schemes and optical
setups, and exploiting various properties of the fluorophores. Here we present a
simple yet versatile STED design for multicolour imaging below the diffraction
limit. A hyperspectral detection arrangement (hyperSTED) collects the
fluorescence in four spectral channels, allowing the separation of four markers
with only one excitation wavelength and a single STED beam. Unmixing of the
different marker signals based on the simultaneous readout of all channels is
performed with a non-negative matrix factorization algorithm. We illustrate the
approach showing four-colour nanoscopy of fixed and living cellular samples.
PMID- 28417976
TI - Revealing inhibition difference between PFI-2 enantiomers against SETD7 by
molecular dynamics simulations, binding free energy calculations and unbinding
pathway analysis.
AB - SETD7 is associated with multiple diseases related signaling pathways. (R)-PFI-2
is the first SETD7 inhibitor with nanomolar inhibitory potency. The activity of
(R)-PFI-2 is about 500 times over that of (S)-PFI-2. Understanding the mechanism
behind this difference will be helpful to discovery and design of more potent
SETD7 inhibitors. A computational study combining molecular dynamics simulation,
binding free energy calculations, and residue interaction network (RIN) was
performed on the (S)-PFI-2/SETD7 and (R)-PFI-2/SETD7 complexes to explore the
molecular mechanism behind the different inhibition activity. The results from
Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculation show (R)
PFI-2 has lower binding free energy. Residues H252, D256, L267, Y335, G336 and
H339 are responsible for the binding of SETD7 to the (R)-PFI-2. RIN analysis
indicates van der Waals interaction is critical for the binding of (R)-PFI-2. The
results from adaptive basing force (ABF) simulation confirm that the free energy
barrier of (R)-PFI-2 dissociating from the SETD7 is larger than that of (S)-PFI
2. (S)-PFI-2 and (R)-PFI-2 dissociate from the SETD7 binding site along different
reaction coordinate and have potential mean of force (PMF) depth. Our simulations
results will be useful to understand molecular mechanism of activity difference
between PFI-2 enantiomers against SETD7.
PMID- 28417978
TI - Efficient Heat Dissipation of Uncooled 400-Gbps (16*25-Gbps) Optical Transceiver
Employing Multimode VCSEL and PD Arrays.
AB - An effective heat dissipation of uncooled 400-Gbps (16*25-Gbps) form-factor
pluggable (CDFP) optical transceiver module employing chip-on-board multimode 25
Gbps vertical-surface-emitting-laser (VCSEL) and 25-Gbps photodiode (PD) arrays
mounted on a brass metal core embedded within a printed circuit board (PCB) is
proposed and demonstrated. This new scheme of the hollow PCB filling with
thermally-dissipated brass metal core was simulated and used for high temperature
and long term stability operation of the proposed 400-Gbps CDFP transceiver.
During one-hour testing, a red-shift of central wavelength by 0.4-nm
corresponding temperature increment of 6.7 degrees C was observed with the brass
core assisted cooler module. Such a temperature change was significantly lower
than that of 28.3 degrees C for the optical transceiver driven with conventional
circuit board. After 100-m distance transmission over a multimode fiber (OM4),
the 400-Gbps CDFP transceiver exhibited dispersion penalty of 2.6-dB, power
budget of ? 3-dB, link loss of ? 0.63-dB, mask margin of 20%, and bit error rate
(BER) of <10-12 with maintained stability more than one hour. The developed 400
Gbps CDFP transceiver module employing low-power consumption VCSEL and PD arrays,
effective coupling lens arrays, and well thermal-dissipation brass metal core is
suitable for use in the low-cost and high-performance data center applications.
PMID- 28417979
TI - Longitudinal assessment of urinary PCA3 for predicting prostate cancer grade
reclassification in favorable-risk men during active surveillance.
AB - BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as
both a one-time and longitudinal measure in men on active surveillance (AS).
METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate
cancer with serial PSA, digital rectal examination (DRE), prostate magnetic
resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens
have also been routinely obtained. Men with multiple PCA3 measures obtained over
?3 years of monitoring were included. Utility of first PCA3 score (fPCA3),
subsequent PCA3 (sPCA3) and change in PCA3 were assessed for prediction of
Gleason grade reclassification (GR, Gleason score >6) during follow-up. RESULTS:
In total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2
years (interquartile range (IQR) 1-3) and from fPCA3 to sPCA3 was 5 years (IQR 4
6). During median follow-up of 6 years (IQR 5-8), 28 men (11%) underwent GR. Men
with GR had higher median fPCA3 (48.0 vs 24.5, P=0.007) and sPCA3 (63.5 vs 36.0,
P=0.002) than those without GR, while longitudinal change in PCA3 did not differ
by GR status (log-normalized rate 0.07 vs 0.06, P=0.53). In a multivariable model
including age, risk classification and PSA density, fPCA3 remained significantly
associated with GR (log(fPCA3) odds ratio=1.77, P=0.04). CONCLUSIONS: PCA3 scores
obtained during AS were higher in men who underwent GR, but the rate of change in
PCA3 over time did not differ by GR status. PCA3 was a significant predictor of
GR in a multivariable model including conventional risk factors, suggesting that
PCA3 provides incremental prognostic information in the AS setting.
PMID- 28417980
TI - Is active surveillance a suitable option for African American men with prostate
cancer? A systemic literature review.
AB - BACKGROUND: Certain patients presenting with either low or very-low-risk prostate
cancer (PCa) can represent a therapeutic dilemma for physicians. The oncologic
outcomes of active surveillance (AS) for men with very-low-risk PCa are overall
excellent. However, there are concerns about AS related to the potential for
upgrading or upstaging. The African American (AA) population is under-represented
in studies evaluating AS outcomes and this is particularly important because of
the unique epidemiology of PCa in AA men. METHODS: A literature review through
the Medline database published from 1990 until August 2015 was performed to
identify studies reporting outcomes of the AA population with low-risk PCa that
underwent either AS or treatment. An additional search for studies on genetic
mechanisms involved in development of PCa in AA men was also performed. RESULTS:
Eleven studies on pathologic results of AA men who would qualify for AS were
identified and in eight of these studies AA race was found to be associated with
adverse pathological outcomes such as positive surgical margins, upgrading or
upstaging. The other three studies reported no significance in these parameters
with respect to race. Five more studies reported outcomes of AS in AA men with
different study end points. AA men were mainly found to have a higher rate of
disease reclassification subsequent to active treatment. The studies on genetic
mechanisms also identified different genetic alterations in the AA population.
CONCLUSIONS: AA men with clinically defined low-risk PCa may have either a higher
grade or volume of cancer that was not detected on routine evaluation. Therefore,
AS among such patients should be approached with caution. We recommend discussing
such risks with AA patients with an acknowledgement that existing favorable
outcomes noted in largely Caucasian populations may not be applicable to AA
patients. We propose a modified evaluation plan for AA patients that includes an
early confirmatory biopsy preceded by an magnetic resonance imaging to optimally
detect occult cancer foci.
PMID- 28417981
TI - Reduced prostate cancer risk with green tea and epigallocatechin 3-gallate intake
among Hong Kong Chinese men.
AB - BACKGROUND: In vitro and in vivo studies suggested that polyphenol
epigallocatechin 3-gallate (EGCG) in tea may have anti-carcinogenic effect on
prostate cells, but this protective effect has less been examined in epidemiology
studies. We aimed to investigate the association between prostate cancer (PCA)
risk and habitual green tea intake among Chinese men in Hong Kong; meanwhile, the
relationship with EGCG was also explored. METHODS: We consecutively recruited 404
PCA cases and 395 controls from the same hospital who had complete data on
habitual tea consumption, including green, oolong, black and pu'er tea. We
reconstructed the level of EGCG intake according to a standard questionnaire and
the analytic values for EGCG extracted from the literature published by Lin et
al. in 2003. We calculated odds ratios (ORs) for tea consumption and EGCG intake
using unconditional multiple logistic regression, and examined their exposure-
response relationships with PCA risk. RESULTS: A total of 32 cases and 50
controls reported habitual green tea drinking, showing an adjusted OR of 0.60
(95% confidence interval (CI): 0.37, 0.98). A moderate excess risk was observed
among the habitual pu'er tea drinkers (OR=1.44, 95% CI: 1.02, 1.91). A
significantly lower intake of EGCG was observed among cases (54.4 mg) than the
controls (72.5 mg), which resulted in an inverse gradient of PCA risk with the
increasing intake of EGCG (test for trend, P=0.015). CONCLUSION: PCA risk among
Chinese men in Hong Kong was inversely associated with green tea consumption and
EGCG intake, but these results need to be replicated in larger studies.
PMID- 28417982
TI - Total and beverage-specific alcohol intake and the risk of aggressive prostate
cancer: a case-control study.
AB - BACKGROUND: Ethanol in alcoholic beverages is a known carcinogen, but its
association with aggressive prostate cancer (APC) is uncertain. Recent studies
have shown a modest increase in risk of APC associated with heavy alcohol intake
while association for beverage types remain inconsistent. METHODS: Using a case
control design and self-administered questionnaire, we examined the association
between APC (high grade and/or advanced stage) and frequency and quantity of
alcohol intake 2 years prior to enrolment. Furthermore, we delineated the
relationships for beverage-specific intakes of beer, red wine, white wine and
spirits. RESULTS: The study included 1282 APC cases and 951 controls. Beer intake
frequency of ?5 days per week was associated with increased risk compared with no
beer intake (odds ratio=1.66, 95% confidence interval: 1.12-2.48) whereas wine
was protective at all frequencies of consumption compared with those with no wine
intake. For every 10 g per week ethanol intake from beer increase, the odds of
advanced PC rose by 3% (OR=1.03, 95% CI: 1.02-1.05). No such increased risk was
observed for red or white wine while a marginal dose-response relationship was
found for spirits (OR=1.03, 95% CI: 0.99-1.07). CONCLUSIONS: Heavy beer and
possibly spirits consumption is associated with increased risk while no dose
response relationship was found for red or white wine. Wine drinkers at all
frequencies have a decreased risk of APC compared with those who did not drink
wine.
PMID- 28417983
TI - An approach to and web-based tool for infectious disease outbreak intervention
analysis.
AB - Infectious diseases are a leading cause of death globally. Decisions surrounding
how to control an infectious disease outbreak currently rely on a subjective
process involving surveillance and expert opinion. However, there are many
situations where neither may be available. Modeling can fill gaps in the decision
making process by using available data to provide quantitative estimates of
outbreak trajectories. Effective reduction of the spread of infectious diseases
can be achieved through collaboration between the modeling community and public
health policy community. However, such collaboration is rare, resulting in a lack
of models that meet the needs of the public health community. Here we show a
Susceptible-Infectious-Recovered (SIR) model modified to include control measures
that allows parameter ranges, rather than parameter point estimates, and includes
a web user interface for broad adoption. We apply the model to three diseases,
measles, norovirus and influenza, to show the feasibility of its use and describe
a research agenda to further promote interactions between decision makers and the
modeling community.
PMID- 28417984
TI - An audience with Jay Bradner.
PMID- 28417985
TI - Viral infections: Targeting host kinases.
PMID- 28417986
TI - Trial watch: Trends in clinical trial design complexity.
PMID- 28417987
TI - Cancer: Identifying synergistic drug combinations.
PMID- 28417988
TI - Analgesia: Designing out opioid side effects.
PMID- 28417989
TI - Antibiotics: Reversing resistance.
PMID- 28417990
TI - G protein-coupled receptors: Novel probe for MRGPRX2.
PMID- 28417991
TI - Esophageal and Small Intestinal Mucosal Integrity in Eosinophilic Esophagitis and
Response to an Elemental Diet.
AB - OBJECTIVES: The esophageal mucosal integrity is impaired in eosinophilic
esophagitis (EoE) and it has been suggested that the duodenal permeability is
increased. The absence of food allergens may restore the integrity. The aims of
this study were to assess duodenal permeability in EoE and to evaluate the effect
of an elemental diet on the esophageal and duodenal integrity. METHODS: In this
prospective study 17 adult EoE patients and 8 healthy controls (HC) were
included. Esophageal biopsy specimens were sampled before and after 4 weeks of
elemental diet to measure eosinophil counts and gene expression of tight junction
and barrier integrity proteins. Esophageal and duodenal impedance were measured
by electrical tissue impedance spectroscopy and Ussing chambers were used to
measure transepithelial resistance (TER) and transepithelial molecule flux. Small
intestinal permeability was measured using a test, measuring lactulose/mannitol
(L/M) ratios. RESULTS: In EoE patients, the esophageal but not the duodenal
integrity was impaired, compared with HC. We observed no significant difference
between L/M ratios of HC and EoE patients. After diet, eosinophil counts
decreased significantly, which was paralleled by normalization of esophageal
impedance and transepithelial molecule flux. The esophageal TER improved
significantly, but did not reach values seen in HC. Esophageal expression of
genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was
impaired at baseline and restored after diet. CONCLUSIONS: An elemental diet
restores esophageal integrity, suggesting that it is at least partly secondary to
allergen exposure. Duodenal integrity seems not to be affected in EoE, and
possibly plays a minor role in its pathophysiology.
PMID- 28417992
TI - Eluxadoline Efficacy in IBS-D Patients Who Report Prior Loperamide Use.
AB - OBJECTIVES: Irritable bowel syndrome with diarrhea (IBS-D) is often managed with
over-the-counter therapies such as loperamide, though with limited success. This
analysis evaluated the efficacy of eluxadoline in patients previously treated
with loperamide in two phase 3 studies. METHODS: Adults with IBS-D (Rome III
criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg)
twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported
loperamide use over the previous year and recorded their rescue loperamide use
during the studies. The primary efficacy end point was the proportion of patients
with a composite response of simultaneous improvement in abdominal pain and
reduction in diarrhea. RESULTS: A total of 2,428 patients were enrolled; 36.0%
reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D
symptom control with loperamide. Among patients with prior loperamide use, a
greater proportion treated with eluxadoline (75 and 100 mg) were composite
responders vs. those treated with placebo with inadequate prior symptom control,
over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively);
similar results were observed over weeks 1-26. When daily rescue loperamide use
was imputed as a nonresponse day, the composite responder rate was still higher
in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12
(P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal
pain. CONCLUSIONS: Eluxadoline effectively and safely treats IBS-D symptoms of
abdominal pain and diarrhea in patients who self-report either adequate or
inadequate control of their symptoms with prior loperamide treatment, with
comparable efficacy and safety irrespective of the use of loperamide as a rescue
medication during eluxadoline treatment.
PMID- 28417993
TI - Corrigendum: Responsiveness of Endoscopic Indices of Disease Activity for Crohn's
Disease.
PMID- 28417996
TI - Addendum.
PMID- 28417994
TI - Trends in Epidemiology of Pediatric Inflammatory Bowel Disease in Canada:
Distributed Network Analysis of Multiple Population-Based Provincial Health
Administrative Databases.
AB - OBJECTIVES: The incidence of pediatric-onset inflammatory bowel disease (IBD) is
increasing worldwide. We used population-based health administrative data to
determine national Canadian IBD incidence, prevalence, and trends over time of
childhood-onset IBD. METHODS: We identified children <16 years (y) diagnosed with
IBD 1999-2010 from health administrative data in five provinces (Alberta,
Manitoba, Nova Scotia, Ontario, Quebec), comprising 79.2% of the Canadian
population. Standardized incidence and prevalence were calculated per 100,000
children. Annual percentage change (APC) in incidence and prevalence were
determined using Poisson regression analysis. Provincial estimates were meta
analyzed using random-effects models to produce national estimates. RESULTS:
5,214 incident cases were diagnosed during the study period (3,462 Crohn's
disease, 1,382 ulcerative colitis, 279 type unclassifiable). The incidence in
Canada was 9.68 (95% CI 9.11 to 10.25) per 100,000 children. Incidence was
similar amongst most provinces, but higher in Nova Scotia. APC in incidence did
not significantly change over the study period in the overall cohort (+2.06%, 95%
CI -0.64% to +4.76%). However, incidence significantly increased in children aged
0-5y (+7.19%, 95% +2.82% to +11.56%). Prevalence at the end of the study period
in Canada was 38.25 (95% CI 35.78 to 40.73) per 100,000 children. Prevalence
increased significantly over time, APC +4.56% (95% CI +3.71% to +5.42%).
CONCLUSIONS: Canada has amongst the highest incidence of childhood-onset IBD in
the world. Prevalence significantly increased over time. Incidence was not
statistically changed with the exception of a rapid increase in incidence in the
youngest group of children.
PMID- 28417995
TI - Corrigendum: Do Primary Care Provider Strategies Improve Patient Participation in
Colorectal Cancer Screening?
AB - This corrects the article DOI: 10.1038/ajg.2017.4.
PMID- 28417997
TI - Iterative expansion microscopy.
AB - We recently developed a method called expansion microscopy, in which preserved
biological specimens are physically magnified by embedding them in a densely
crosslinked polyelectrolyte gel, anchoring key labels or biomolecules to the gel,
mechanically homogenizing the specimen, and then swelling the gel-specimen
composite by ~4.5* in linear dimension. Here we describe iterative expansion
microscopy (iExM), in which a sample is expanded ~20*. After preliminary
expansion a second swellable polymer mesh is formed in the space newly opened up
by the first expansion, and the sample is expanded again. iExM expands biological
specimens ~4.5 * 4.5, or ~20*, and enables ~25-nm-resolution imaging of cells and
tissues on conventional microscopes. We used iExM to visualize synaptic proteins,
as well as the detailed architecture of dendritic spines, in mouse brain
circuitry.
PMID- 28417998
TI - Marker-free coselection for CRISPR-driven genome editing in human cells.
AB - Targeted genome editing enables the creation of bona fide cellular models for
biological research and may be applied to human cell-based therapies. Therefore,
broadly applicable and versatile methods for increasing its efficacy in cell
populations are highly desirable. We designed a simple and robust coselection
strategy for enrichment of cells with either nuclease-driven nonhomologous end
joining (NHEJ) or homology-directed repair (HDR) events by harnessing the
multiplexing capabilities of CRISPR-Cas9 and Cpf1 systems. Selection for dominant
alleles of the ubiquitous sodium/potassium pump (Na+/K+ ATPase) that rendered
cells resistant to ouabain was used to enrich for custom genetic modifications at
another unlinked locus of interest, thereby effectively increasing the recovery
of engineered cells. The process is readily adaptable to transformed and primary
cells, including hematopoietic stem and progenitor cells. The use of universal
CRISPR reagents and a commercially available small-molecule inhibitor streamlines
the incorporation of marker-free genetic changes in human cells.
PMID- 28418000
TI - SCnorm: robust normalization of single-cell RNA-seq data.
AB - The normalization of RNA-seq data is essential for accurate downstream inference,
but the assumptions upon which most normalization methods are based are not
applicable in the single-cell setting. Consequently, applying existing
normalization methods to single-cell RNA-seq data introduces artifacts that bias
downstream analyses. To address this, we introduce SCnorm for accurate and
efficient normalization of single-cell RNA-seq data.
PMID- 28418001
TI - Effects of calcination temperature for rate capability of triple-shelled ZnFe2O4
hollow microspheres for lithium ion battery anodes.
AB - Triple-shelled ZnFe2O4 hollow microspheres (ZFO) as anode materials for lithium
ion battery are prepared through a one-pot hydrothermal reaction using the
composite solution consisting of sucrose in water and metal ions in ethylene
glycol (EG), followed by different calcination processes. The architectures of
ZFO micro spheres are differently synthesized through a mutual cooperation of
inward and outward ripening with three different calcination temperatures. Thin
triple-shelled ZnFe2O4 hollow microspheres calcined at 450 degrees C (ZFO-450)
delivers a high reversible capacity of 932 mA h g-1 at a current density of 2 A g
1 even at the 200th cycle without obvious decay. Furthermore, ZFO-450 delivers
1235, 1005, 865, 834, and 845 mA h g-1 at high current densities of 0.5, 2, 5,
10, and 20 A g-1 after 100 cycles. Thin triple-shelled hollow microsphere
prepared at an optimum calcination temperature provides exceptional rate
capability and outstanding rate retention due to (i) the formation of
nanoparticles leading to thin shell with morphological integrity, (ii) the facile
mass transfer by thin shell with mesoporous structure, and (iii) the void space
with macroporous structure alleviating volume change occurring during cycling.
PMID- 28417999
TI - A tiling-deletion-based genetic screen for cis-regulatory element identification
in mammalian cells.
AB - Millions of cis-regulatory elements are predicted to be present in the human
genome, but direct evidence for their biological function is scarce. Here we
report a high-throughput method, cis-regulatory element scan by tiling-deletion
and sequencing (CREST-seq), for the unbiased discovery and functional assessment
of cis-regulatory sequences in the genome. We used it to interrogate the 2-Mb
POU5F1 locus in human embryonic stem cells, and identified 45 cis-regulatory
elements. A majority of these elements have active chromatin marks, DNase
hypersensitivity, and occupancy by multiple transcription factors, which confirms
the utility of chromatin signatures in cis-element mapping. Notably, 17 of them
are previously annotated promoters of functionally unrelated genes, and like
typical enhancers, they form extensive spatial contacts with the POU5F1 promoter.
These results point to the commonality of enhancer-like promoters in the human
genome.
PMID- 28418002
TI - Immune Tissue Print and Immune Capture-PCR for Diagnosis and Detection of
Candidatus Liberibacter Asiaticus.
AB - 'Candidatus Liberibacter asiaticus' (CaLas), associated with citrus Huanglongbing
(HLB), is a non culturable member of the alpha-proteobacteria. In this study
serologically based methods for the detection of CaLas were developed. An anti
outer membrane protein A (OmpA) polyclonal antibody previously produced (in our
laboratory) was highly effective for the detection of CaLas from citrus tissues
in a simple tissue printing format. The antibody was also used to capture
bacteria from periwinkle extracts. About 80% of all field samples analyzed tested
positive with both immune tissue printing and qPCR; whereas 95% were positive
with at least one of these two methods. When asymptomatic citrus tissues were
tested, the tissue printing method gave a higher rate of detection (83%) than the
qPCR method (64%). This is consistent with a lower concentration of CaLas DNA,
but a higher proportion of viable cells, in the asymptomatic tissues. The immune
tissue printing method also highlights the detail of the spatial distribution of
'Ca. Liberibacter asiaticus' in diseased citrus tissues. Both the immune capture
PCR and immune tissue printing methods offer the advantages of low cost, high
throughput, ease of scaling for multiple samples and simplicity over current PCR
based methods for the detection of 'Ca. Liberibacter asiaticus'.
PMID- 28418003
TI - Toll-like receptor polymorphisms compromise the inflammatory response against
bacterial antigen translocation in cirrhosis.
AB - Bacterial translocation is associated with clinically relevant complications in
cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the
soluble response against these episodes. Consecutive patients with cirrhosis and
ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9
rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide,
bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified
in serum samples. In vitro response against specific ligands in variant TLR
genotypes was evaluated. One hundred and fourteen patients were included. Variant
TLR-2, TLR-4 and TLR-9 SNP genotypes were associated with significantly increased
serum levels of LTA, LPS and bacterial-DNA. TNF-alpha, IL-6 and nitric oxide
serum levels were significantly decreased in all variant TLR genotyped patients.
Cytokine levels were significantly less upregulated in response to specific TLR
ligands in patients with all variant vs wildtype TLR genotypes. Although in vitro
gene expression levels of all wildtype and variant TLRs were similar, MyD88 and
NFkB were significantly downregulated in cells from TLR-variant genotyped
patients in response to their ligands. Variant TLR genotypes are associated with
an increased circulating antigen burden and a decreased proinflammatory response
in cirrhosis. This immunodeficiency may facilitate bacteria-related complications
in cirrhosis and enhance TLR targeting for its management.
PMID- 28418005
TI - Simulated climate effects of desert irrigation geoengineering.
AB - Geoengineering, the deliberate large-scale manipulation of earth's energy balance
to counteract global warming, is an attractive proposition for sparsely populated
deserts. We use the BNU and UVic Earth system models to simulate the effects of
irrigating deserts under the RCP8.5 scenario. Previous studies focused on
increasing desert albedo to reduce global warming; in contrast we examine how
extending afforestation and ecological projects, that successfully improve
regional environments, fair for geoengineering purposes. As expected desert
irrigation allows vegetation to grow, with bare soil or grass gradually becoming
shrub or tree covered, with increases in terrestrial carbon storage of 90.3 Pg C
(UVic-ESCM) - 143.9 Pg C (BNU-ESM). Irrigating global deserts makes the land
surface temperature decrease by 0.48 degrees C and land precipitation increase
by 100 mm yr-1. In the irrigated areas, BNU-ESM simulates significant cooling of
up to 4.2 degrees C owing to the increases in low cloud and latent heat which
counteract the warming effect due to decreased surface albedo. Large volumes of
water would be required to maintain global desert irrigation, equivalent 10
mm/year of global sea level (BNU-ESM) compensate for evapotranspiration losses.
Differences in climate responses between the deserts prompt research into
tailored albedo-irrigation schemes.
PMID- 28418004
TI - Host Determinants of Expression of the Helicobacter pylori BabA Adhesin.
AB - Expression of the Helicobacter pylori blood group antigen binding adhesin A
(BabA) is more common in strains isolated from patients with peptic ulcer disease
or gastric cancer, rather than asymptomatic colonization. Here we used mouse
models to examine host determinants that affect H. pylori BabA expression. BabA
expression was lost by phase variation as frequently in WT mice as in RAG2-/-
mice that do not have functional B or T cells, and in MyD88-/-, TLR2-/- and TLR4
/- mice that are defective in toll like receptor signaling. The presence of other
bacteria had no effect on BabA expression as shown by infection of germ free
mice. Moreover, loss of BabA expression was not dependent on Leb expression or
the capacity of BabA to bind Leb. Surprisingly, gender was the host determinant
most associated with loss of BabA expression, which was maintained to a greater
extent in male mice and was associated with greater bacterial load. These results
suggest the possibility that loss of BabA expression is not driven by adaptive
immunity or toll-like receptor signaling, and that BabA may have other,
unrecognized functions in addition to serving as an adhesin that binds Leb.
PMID- 28418006
TI - Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer.
AB - Radiomics characterizes tumor phenotypes by extracting large numbers of
quantitative features from radiological images. Radiomic features have been shown
to provide prognostic value in predicting clinical outcomes in several studies.
However, several challenges including feature redundancy, unbalanced data, and
small sample sizes have led to relatively low predictive accuracy. In this study,
we explore different strategies for overcoming these challenges and improving
predictive performance of radiomics-based prognosis for non-small cell lung
cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who
underwent stereotactic body radiotherapy were used to predict recurrence, death,
and recurrence-free survival using a comprehensive radiomics analysis. Different
feature selection and predictive modeling techniques were used to determine the
optimal configuration of prognosis analysis. To address feature redundancy,
comprehensive analysis indicated that Random Forest models and Principal
Component Analysis were optimum predictive modeling and feature selection
methods, respectively, for achieving high prognosis performance. To address
unbalanced data, Synthetic Minority Over-sampling technique was found to
significantly increase predictive accuracy. A full analysis of variance showed
that data endpoints, feature selection techniques, and classifiers were
significant factors in affecting predictive accuracy, suggesting that these
factors must be investigated when building radiomics-based predictive models for
cancer prognosis.
PMID- 28418007
TI - Saturated fatty acids induce development of both metabolic syndrome and
osteoarthritis in rats.
AB - The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA,
C12:0), myristic acid (MA, C14:0), palmitic acid (PA, C16:0) and stearic acid
(SA, C18:0). The aim of this study was to investigate whether diets containing
individual SFA together with excess simple carbohydrates induce osteoarthritis
(OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats
were given either a corn starch diet or a diet composed of simple carbohydrates
together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef
tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also
exhibited cartilage degradation and subchondral bone changes similar to OA. In
contrast, replacement of beef tallow with LA decreased signs of metabolic
syndrome together with decreased cartilage degradation. Furthermore, PA and SA
but not LA increased release of matrix sulphated proteoglycans in cultures of
bovine cartilage explants or human chondrocytes. In conclusion, we have shown
that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like
knee changes. Thus, diets containing SFA are strongly relevant to the development
or prevention of both OA and metabolic syndrome.
PMID- 28418008
TI - Quantitative analyses of the global proteome and phosphoproteome reveal the
different impacts of propofol and dexmedetomidine on HT22 cells.
AB - Propofol and dexmedetomidine are both commonly used anaesthetics. Although they
employ two different mechanisms to induce anaesthesia, both compounds influence
the hippocampus and the HT22 cell line. HT22 cells are broadly used in
neurobiological research. In this study, we assessed the effects of propofol and
dexmedetomidine on signalling in HT22 cells. Using the SILAC (stable isotope
labelling with amino acids in cell culture) labelling technique, IMAC
(immobilized metal affinity chromatography) enrichment and high-resolution LC
MS/MS (liquid chromatography tandem mass spectrometry) analysis, we investigated
the quantitative proteome and phosphoproteome in HT22 cells treated with propofol
or dexmedetomidine. In total, 4,527 proteins and 6,824 phosphosites were
quantified in cells treated with these two anaesthetics. With the assistance of
intensive bioinformatics, the propofol and dexmedetomidine treatments were shown
to induce distinct proteome and phosphoproteome profiles in HT22 cells.
Consistent with our bioinformatics analysis, dexmedetomidine had a smaller effect
than propofol on cell survival. These findings deepen our understanding of drug
induced anaesthesia.
PMID- 28418009
TI - Effect of UMOD genotype on long-term graft survival after kidney transplantation
in patients treated with cyclosporine-based therapy.
AB - The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with
renal function, chronic kidney disease and hypertension with the minor T-allele
showing a protective effect. Hypertension and nephrotoxicity are adverse effects
of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor
kidneys associates with long-term graft survival in 393 Caucasian patients with
stable graft function for more than 10 weeks after kidney transplantation treated
with a cyclosporine-based maintenance therapy (mean graft survival 9 years).
Presence of the donor T-allele had no effect on blood pressure, serum creatinine
1 year after transplantation, and on number of acute graft rejections during the
first year. No significant effect on overall graft survival was observed in
Kaplan-Meier analysis (P=0.65). In death-censored adjusted multivariate analysis,
presence of donor T-allele associated with a significant lower hazard ratio of
0.67 (95% confidence interval: 0.46-0.97, P=0.05) for graft loss. This protective
effect of the donor T-allele on graft loss observed in multivariate adjusted
analysis justifies further investigations including patients treated with similar
or other immunosuppressive regimens.
PMID- 28418010
TI - Interaction between NUDT15 and ABCC4 variants enhances intolerability of 6
mercaptopurine in Japanese patients with childhood acute lymphoblastic leukemia.
AB - 6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic
leukemia (ALL) treatment. Some candidate gene variants are associated with its
toxicities, but the major variants and effects of combined variants remain
unclear. We used Cox regression analysis to evaluate the time-dependent
association between candidate variants and the cumulative incidence of 6-MP
intolerability in 95 Japanese patients. The major risk factors for severe
leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi
covariate analysis (P<0.05). NUDT15 intermediate activity variant, that is,
heterozygous rs116855232 or rs186364861 variant, and the ABCC4 rs3765534 variant
showed leukopenia more frequently than either variant alone. All patients with
both the intermediate activity NUDT15 variant and the ABCC4 rs3765534 variant
suffered from leukopenia, and 57.1% patients required 50% protocol dose by day
168. These data indicate that NUDT15 and ABCC4 are major factors for 6-MP
intolerability and that the interaction between these variants enhances
intolerability to 6-MP.
PMID- 28418011
TI - More than 25 years of genetic studies of clozapine-induced agranulocytosis.
AB - Clozapine is one of the most effective atypical antipsychotic drugs prescribed to
patients with treatment-resistant schizophrenia. Approximately 1% of patients
experience potential life-threatening adverse effects in the form of
agranulocytosis, greatly hindering its applicability in clinical practice. The
etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is
thought to be a heritable trait. We reviewed the genetic studies of CIA published
thus far. One recurrent finding from early candidate gene study to more recent
genome-wide analysis is that of the involvement of human leukocyte antigen locus.
We conclude that CIA is most likely a complex, polygenic trait, which may hamper
efforts to the development of a genetic predictor test with clinical relevance.
To decipher the genetic architecture of CIA, it is necessary to apply more
rigorous standards of phenotyping and study much larger sample sizes.
PMID- 28418013
TI - A graphene based frequency quadrupler.
AB - Benefit from exceptional electrical transport properties, graphene receives
worldwide attentions, especially in the domain of high frequency electronics. Due
to absence of effective bandgap causing off-state the device, graphene material
is extraordinarily suitable for analog circuits rather than digital applications.
With this unique ambipolar behavior, graphene can be exploited and utilized to
achieve high performance for frequency multipliers. Here, dual-gated graphene
field-effect transistors have been firstly used to achieve frequency quadrupling.
Two Dirac points in the transfer curves of the designed GFETs can be observed by
tuning top-gate voltages, which is essential to generate the fourth harmonic. By
applying 200 kHz sinusoid input, arround 50% of the output signal radio frequency
power is concentrated at the desired frequency of 800 kHz. Additionally, in
suitable operation areas, our devices can work as high performance frequency
doublers and frequency triplers. Considered both simple device structure and
potential superhigh carrier mobility of graphene material, graphene-based
frequency quadruplers may have lots of superiorities in regards to ultrahigh
frequency electronic applications in near future. Moreover, versatility of carbon
material system is far-reaching for realization of complementary metal-oxide
semiconductor compatible electrically active devices.
PMID- 28418012
TI - CYP3A4 is a crosslink between vitamin D and calcineurin inhibitors in solid organ
transplant recipients: implications for bone health.
AB - The use of calcineurin inhibitors (CNIs) and vitamin D deficiency may contribute
to the pathogenesis of post-transplant bone disease. CNIs and 1,25
dihydroxyvitamin D3 (1,25(OH)2D3) are substrates of the drug-metabolizing enzyme
CYP3A4. This review summarizes the indications for the use of activated vitamin D
analogs in post-transplant care and the current knowledge on the impact of CNIs
on bone. We searched for clinical evidence of the interaction between CNIs and
1,25(OH)2D3. We also provide an overview of the literature on the interplay
between vitamin D metabolism and CYP3A4 in experimental and clinical settings and
discuss its possible implications for solid organ transplant recipients. In
conclusion, there is a body of evidence on the interplay between vitamin D and
the drug-metabolizing enzyme CYP3A4, which may have therapeutic implications.
PMID- 28418014
TI - The relationship between allergic status and adenotonsillar regrowth: a
retrospective research on children after adenotonsillectomy.
AB - Adenotonsillar regrowth in children after adenotonsillectomy (T&A) for
obstructive sleep apnea (OSA) is often seen in clinical treatment, however, the
relationship between allergic disease and adenotonsillar regrowth remains
unclear. In this retrospective study, children were assigned to either the
recurrence or control group, and subdivided by age at operation. Among children
over 36 months, those in the recurrence group had more allergic disease and
higher IgE, IL-4, and IL-5 levels than the same-aged children in control group.
The Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores for
nasal symptoms and activity were higher in children older than 36 months in
recurrence group. The results of immunohistochemistry and immunofluorescence
showed that FoxP3+ cells (Tregs) were less, while GATA3+ cells (Th2 cells) were
more in recurrence group for all ages. Allergic status and low levels of FoxP3
were proved as independent risk factors for adenotonsillar regrowth by
multivariate logistic regression. These results indicate that allergic disease is
a risk factor for adenotonsillar regrowth in children following T&A for OSA, and
this risk increases with age. The decreased level of Tregs and subsequent changes
in immune function play an important role in the pathogenesis of adenotonsillar
regrowth.
PMID- 28418015
TI - Diabetes: LMPTP inhibitors - potential treatment for type 2 diabetes?
PMID- 28418016
TI - Pituitary function: Pulsatile GnRH therapy in CCPHD.
PMID- 28418017
TI - Accessing Forbidden Glass Regimes through High-Pressure Sub-Tg Annealing.
AB - Density and hardness of glasses are known to increase upon both compression at
the glass transition temperature (Tg) and ambient pressure sub-Tg annealing.
However, a serial combination of the two methods does not result in higher
density and hardness, since the effect of compression is countered by subsequent
annealing and vice versa. In this study, we circumvent this by introducing a
novel treatment protocol that enables the preparation of high-density, high
hardness bulk aluminosilicate glasses. This is done by first compressing a sodium
magnesium aluminosilicate glass at 1 GPa at Tg, followed by sub-Tg annealing in
situ at 1 GPa. Through density, hardness, and heat capacity measurements, we
demonstrate that the effects of hot compression and sub-Tg annealing can be
combined to access a "forbidden glass" regime that is inaccessible through
thermal history or pressure history variation alone. We also study the relaxation
behavior of the densified samples during subsequent ambient pressure sub-Tg
annealing. Density and hardness are found to relax and approach their ambient
condition values upon annealing, but the difference in relaxation time of density
and hardness, which is usually observed for hot compressed glasses, vanishes for
samples previously subjected to high-pressure sub-Tg annealing. This confirms the
unique configurational state of these glasses.
PMID- 28418018
TI - Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the
Cerebral Cortex of Sanfilippo Syndrome IIIA Mice.
AB - Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that
specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The
accumulation of heparan sulfate results in neurological symptoms, culminating in
extensive neurodegeneration and early death. To study the impact of storage in
postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the
enzyme sulfamidase. We show that changes occur in excitatory postsynaptic
structure and function in the somatosensory cortex prior to signs of
neurodegeneration. These changes coincide with accumulation of heparan sulfate
with characteristic non-reducing ends, which is present at birth in the mutant
mice. Accumulation of heparan sulfate was also detected in primary cultures of
cortical neural cells, especially astrocytes. Accumulation of heparan sulfate in
cultured astrocytes corresponded with augmented extracellular heparan sulfate and
glypican 4 levels. Heparan sulfate from the cerebral cortex of MPS IIIA mice
showed enhanced ability to increase glutamate AMPA receptor subunits at the cell
surface of wild type neurons. These data support the idea that abnormalities in
heparan sulfate content and distribution contribute to alterations in
postsynaptic function. Our findings identify a disease-induced developmental
phenotype that temporally overlaps with the onset of behavioral changes in a
mouse model of MPS IIIA.
PMID- 28418020
TI - Pathogenic CD4+ T cells regulating B-cell differentiation in autoimmunity: not
exactly Tfh cells.
PMID- 28418019
TI - Live imaging of H3K9 acetylation in plant cells.
AB - Proper regulation of histone acetylation is important in development and cellular
responses to environmental stimuli. However, the dynamics of histone acetylation
at the single-cell level remains poorly understood. Here we established a
transgenic plant cell line to track histone H3 lysine 9 acetylation (H3K9ac) with
a modification-specific intracellular antibody (mintbody). The H3K9ac-specific
mintbody fused to the enhanced green fluorescent protein (H3K9ac-mintbody-GFP)
was introduced into tobacco BY-2 cells. We successfully demonstrated that H3K9ac
mintbody-GFP interacted with H3K9ac in vivo. The ratio of nuclear/cytoplasmic
H3K9ac-mintbody-GFP detected in quantitative analysis reflected the endogenous
H3K9ac levels. Under chemically induced hyperacetylation conditions with histone
deacetylase inhibitors including trichostatin A, Ky-2 and Ky-14, significant
enhancement of H3K9ac was detected by H3K9ac-mintbody-GFP dependent on the
strength of inhibitors. Conversely, treatment with a histone acetyltransferase
inhibitor, C646 caused a reduction in the nuclear to cytoplasmic ratio of H3K9ac
mintbody-GFP. Using this system, we assessed the environmental responses of
H3K9ac and found that cold and salt stresses enhanced H3K9ac in tobacco BY-2
cells. In addition, a combination of H3K9ac-mintbody-GFP with 5-ethynyl-2'
deoxyuridine labelling confirmed that H3K9ac level is constant during interphase.
PMID- 28418021
TI - Prion disease: Abeta pathology in human growth hormone recipients.
PMID- 28418022
TI - The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in
encephalitis.
AB - The discovery, in 2010, of autoantibodies against the extracellular proteins LGI1
and Caspr2 facilitated a change of view regarding the clinical importance of
voltage-gated potassium channel (VGKC) antibodies. Currently, these antibodies
are all classified as VGKC-complex antibodies, and are commonly considered to
have a similar clinical value. However, studies from the past few years show that
the immune responses mediated by these antibodies have differing clinical
relevance. Here, we review the clinical importance of these immune responses in
three settings: patients with anti-LGI1 antibodies, patients with anti-Caspr2
antibodies, and patients with antibodies against the VGKC complex that lack LGI1
and Caspr2 specificity. Antibodies against LGI1 and Caspr2 are associated with
different but well-defined syndromes, whereas the clinical importance of VGKC
complex antibodies without LGI1 and Caspr2 specificity is questionable. We
describe each of these syndromes, discuss the function of the target antigens and
review the limited paediatric literature on the topic. The findings emphasize the
importance of defining these disorders according to the molecular identity of the
targets (LGI1 or Caspr2), and caution against the use of VGKC-complex antibodies
for the diagnosis and treatment of patients without further definition of the
antigen.
PMID- 28418024
TI - Alzheimer disease: Neurofilament light in the blood marks Alzheimer degeneration.
PMID- 28418025
TI - Cerebrovascular disease: CeAD and migraine - an association built on shifting
sands.
PMID- 28418023
TI - Human induced pluripotent stem cells for modelling neurodevelopmental disorders.
AB - We currently have a poor understanding of the pathogenesis of neurodevelopmental
disorders, owing to the fact that postmortem and imaging studies can only measure
the postnatal status quo and offer little insight into the processes that give
rise to the observed outcomes. Human induced pluripotent stem cells (hiPSCs)
should, in principle, prove powerful for elucidating the pathways that give rise
to neurodevelopmental disorders. hiPSCs are embryonic-stem-cell-like cells that
can be derived from somatic cells. They retain the unique genetic signature of
the individual from whom they were derived, and thus enable researchers to
recapitulate that individual's idiosyncratic neural development in a dish. In the
case of individuals with disease, we can re-enact the disease-altered trajectory
of brain development and examine how and why phenotypic and molecular
abnormalities arise in these diseased brains. Here, we review hiPSC biology and
possible experimental designs when using hiPSCs to model disease. We then discuss
existing hiPSC models of neurodevelopmental disorders. Our hope is that, as some
studies have already shown, hiPSCs will illuminate the pathophysiology of
developmental disorders of the CNS and lead to therapeutic options for the
millions that are affected by these conditions.
PMID- 28418026
TI - The Cac2 subunit is essential for productive histone binding and nucleosome
assembly in CAF-1.
AB - Nucleosome assembly following DNA replication controls epigenome maintenance and
genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone
responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural
and functional details for this chaperone complex and its interaction with
histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass
spectrometry, combined with in vitro and in vivo mutagenesis studies, we
identified the regions involved in the direct interaction between the yeast CAF-1
subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large
subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is
mediated by a composite interface, shaped by Cac1-bound Cac2 and the Cac1 acidic
region. Cac2 is indispensable for productive histone binding, while deletion of
Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These
results define direct structural roles for yeast CAF-1 subunits and uncover a
previously unknown critical function of the middle subunit in CAF-1.
PMID- 28418027
TI - Accurate and reproducible invasive breast cancer detection in whole-slide images:
A Deep Learning approach for quantifying tumor extent.
AB - With the increasing ability to routinely and rapidly digitize whole slide images
with slide scanners, there has been interest in developing computerized image
analysis algorithms for automated detection of disease extent from digital
pathology images. The manual identification of presence and extent of breast
cancer by a pathologist is critical for patient management for tumor staging and
assessing treatment response. However, this process is tedious and subject to
inter- and intra-reader variability. For computerized methods to be useful as
decision support tools, they need to be resilient to data acquired from different
sources, different staining and cutting protocols and different scanners. The
objective of this study was to evaluate the accuracy and robustness of a deep
learning-based method to automatically identify the extent of invasive tumor on
digitized images. Here, we present a new method that employs a convolutional
neural network for detecting presence of invasive tumor on whole slide images.
Our approach involves training the classifier on nearly 400 exemplars from
multiple different sites, and scanners, and then independently validating on
almost 200 cases from The Cancer Genome Atlas. Our approach yielded a Dice
coefficient of 75.86%, a positive predictive value of 71.62% and a negative
predictive value of 96.77% in terms of pixel-by-pixel evaluation compared to
manually annotated regions of invasive ductal carcinoma.
PMID- 28418028
TI - An algorithm to predict advanced proximal colorectal neoplasia in Chinese
asymptomatic population.
AB - This study aims to develop and validate a new algorithm that incorporates distal
colonoscopic findings to predict advanced proximal neoplasia (APN) in a Chinese
asymptomatic population. We collected age, gender, and colonoscopic findings from
a prospectively performed colonoscopy study between 2013 and 2015 in a large
hospital-based endoscopy unit in Shanghai, China. Eligible subjects were
allocated to a derivation group (n = 3,889) and validation group (n = 1,944) by
random sampling. A new index for APN and its cut-off level were evaluated from
the derivation cohort by binary logistic regression. The model performance was
tested in the validation cohort using area under the curve (AUC). Age, gender,
and distal finding were found to be independent predictors of APN in the
derivation cohort (p < 0.001). Subjects were categorized into Average Risk (AR)
and High Risk (HR) based on a cut-off score of 2. The AUC of the derivation and
validation cohorts were 0.801 (0.754-0.847) and 0.722 (0.649-0.794),
respectively. In the validation cohort, those in the HR group had a 3.57 fold
higher risk of APN when compared with the AR group (P < 0.001), requiring 18 (95%
CI = 12-28) follow-up colonoscopies to detect 1 APN. This new clinical index is
useful to stratify APN risk in Chinese population.
PMID- 28418029
TI - TmCactin plays an important role in Gram-negative and -positive bacterial
infection by regulating expression of 7 AMP genes in Tenebrio molitor.
AB - Cactin was originally identified as an interactor of the Drosophila IkappaB
factor Cactus and shown to play a role in controlling embryonic polarity and
regulating the NF-kappaB signaling pathway. While subsequent studies have
identified the roles for Cactin in the mammalian immune response, the immune
function of Cactin in insects has not been described yet. Here, we identified a
Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and
characterized its functional role in innate immunity. TmCactin was highly
expressed in prepupa to last instar stages, and its expression was high in the
integument and Malpighian tubules of last instar larvae and adults. TmCactin was
induced in larvae after infection with different pathogens and detectable within
3 hours of infection. The highest levels of TmCactin expression were detected at
9 hours post infection. TmCactin RNAi significantly decreased the survival rates
of larvae after challenge with Escherichia coli and Staphylococcus aureus, but
had no significant effect after challenge with Candida albicans. Furthermore,
TmCactin RNAi significantly reduced the expression of seven antimicrobial peptide
genes (AMPs) after bacterial challenge. Our results suggest that TmCactin may
serve as an important regulator of innate immunity, mediating AMP responses
against both Gram-positive and Gram-negative bacteria in T. molitor.
PMID- 28418030
TI - The BMP2 nuclear variant, nBMP2, is expressed in mouse hippocampus and impacts
memory.
AB - The novel nuclear protein nBMP2 is synthesized from the BMP2 gene by
translational initiation at an alternative start codon. We generated a targeted
mutant mouse, nBmp2NLStm, in which the nuclear localization signal (NLS) was
inactivated to prevent nuclear translocation of nBMP2 while still allowing the
normal synthesis and secretion of the BMP2 growth factor. These mice exhibit
abnormal muscle function due to defective Ca2+ transport in skeletal muscle. We
hypothesized that neurological function, which also depends on intracellular Ca2+
transport, could be affected by the loss of nBMP2. Age-matched nBmp2NLStm and
wild type mice were analyzed by immunohistochemistry, behavioral tests, and
electrophysiology to assess nBMP2 expression and neurological function.
Immunohistochemical staining of the hippocampus detected nBMP2 in the nuclei of
CA1 neurons in wild type but not mutant mice, consistent with nBMP2 playing a
role in the hippocampus. Mutant mice showed deficits in the novel object
recognition task, suggesting hippocampal dysfunction. Electrophysiology
experiments showed that long-term potentiation (LTP) in the hippocampus, which is
dependent on intracellular Ca2+ transport and is thought to be the cellular
equivalent of learning and memory, was impaired. Together, these results suggest
that nBMP2 in the hippocampus impacts memory formation.
PMID- 28418031
TI - Serum Concentration of HDL Particles Predicts Mortality in Acute Heart Failure
Patients.
AB - Clinical studies have shown that assessing circulating concentrations of high
density lipoprotein (HDL) particles by nuclear magnetic resonance (NMR)
spectroscopy is superior to HDL-cholesterol in predicting cardiovascular risk. We
tested the hypothesis that circulating concentrations of HDL particles predict 3
month mortality of patients with acute heart failure (AHF). Out of 152 included
patients, 52% were female, additionally the mean patient age was 75.2 +/- 10.3
years, and three-month mortality was 27%. Serum lipoprotein profile at admission
was determined by NMR spectroscopy. Univariate logistic regression analyses
revealed a significant inverse association of total (odds ratio (OR) 0.38 per 1
SD increase, 95% confidence interval (CI) 0.23-0.60, p < 0.001) and small HDL
particle concentrations (OR 0.35 per 1-SD increase, 95% CI 0.19-0.60, p < 0.001)
with 3-month mortality, whereas concentrations of large HDL particles (p = 0.353)
or HDL-cholesterol (p = 0.107) showed no significant association. After
adjustment for age, sex, mean arterial pressure, low-density lipoprotein
cholesterol, glomerular filtration rate, urea, and N-terminal pro-brain
natriuretic peptide, both the total and small HDL particle concentrations
remained significantly associated with 3-month mortality. Based on our results,
we conclude that total and small HDL particle concentrations strongly and
independently predict 3-month mortality in AHF patients.
PMID- 28418032
TI - A New Approach to Evaluating Aberrant DNA Methylation Profiles in Hepatocellular
Carcinoma as Potential Biomarkers.
AB - Hypermethylation of CpG islands in the promoter region of tumor suppressor genes
(TSGs) and their subsequent silencing is thought to be one of the main mechanisms
of carcinogenesis. MBD2b enrichment coupled with a NimbleGen array was applied to
examine the genome-wide CpG island methylation profile of hepatocellular
carcinoma (HCC). Hypermethylated DNA of 58 pairs of HCC and adjacent tissue
samples was enriched and hybridized in the same array. Aberrant hypermethylated
peaks of HCC and adjacent tissues were screened and annotated after data
processing using NimbleScan2.5 and our newly developed Weighting and Scoring
(WAS) method, respectively. Validation using bisulfite sequencing of randomly
selected ANKRD45, APC, CDX1, HOXD3, PTGER and TUBB6 genes demonstrated
significant hypermethylation modification in HCC samples, consistent with the
array data.
PMID- 28418033
TI - A genome-wide SNP-based genetic map and QTL mapping for agronomic traits in
Chinese cabbage.
AB - The aim of this work was to construct a high-resolution genetic map for the
dissection of complex morphological and agronomic traits in Chinese cabbage
(Brassica rapa L. syn. B. campestris). Chinese cabbage, an economically important
vegetable, is a good model plant for studies on the evolution of morphologic
variation. Herein, two high-generation inbred Chinese cabbage lines,
'Huangxiaoza' and 'Bqq094-11', were crossed. Then restriction-site-associated DNA
sequencing (RAD-seq) was performed on the parents and 120 F2 individuals. A
genetic map containing 711 bins representing 3985 single nucleotide polymorphism
(SNP) markers was constructed. By using WinQTL with composite interval mapping
(CIM) and mixed-model based composite interval mapping (MCIM) analysis via
QTLNetwork, quantitative trait loci (QTL) linked to 16 genetic traits related to
plant size, color and leaf characteristics were mapped to 10 linkage groups. The
high density genetic map and QTL identified for morphological and agronomic
traits lay the groundwork for functional gene mapping, map-based cloning and
marker-assisted selection (MAS) in Chinese cabbage.
PMID- 28418034
TI - Light- and circadian-controlled genes respond to a broad light spectrum in Puffer
Fish-derived Fugu eye cells.
AB - Some cell lines retain intrinsic phototransduction pathways to control the
expression of light-regulated genes such as the circadian clock gene. Here we
investigated the photosensitivity of a Fugu eye, a cell line established from the
eye of Takifugu rubripes, to examine whether such a photosensitive nature is
present. Microarray analysis identified 15 genes that showed blue light-dependent
change at the transcript level. We investigated temporal profiles of the light
induced genes, as well as Cry and Per, under light-dark, constant light (LL), and
constant dark (DD) conditions by quantitative RT-PCR. Transcript levels of Per1a
and Per3 genes showed circadian rhythmic changes under both LL and DD conditions,
while those of Cry genes were controlled by light. All genes examined, including
DNA-damage response genes and photolyase genes, were upregulated not only by blue
light but also green and red light, implying the contribution of multiple
photopigments. The present study is the first to identify a photosensitive clock
cell line originating from a marine fish. These findings may help to characterize
the molecular mechanisms underlying photic synchronization of the physiological
states of fishes to not only daily light-dark cycles but also to various marine
environmental cycles such as the lunar or semi-lunar cycle.
PMID- 28418035
TI - Chronic social defeat reduces myelination in the mouse medial prefrontal cortex.
AB - The medial prefrontal cortex (mPFC) plays a key role in top-down control of the
brain's stress axis, and its structure and function are particularly vulnerable
to stress effects, which can lead to depression in humans and depressive-like
states in animals. We tested whether chronic social defeat produces structural
alterations in the mPFC in mice. We first performed a microarray analysis of mPFC
gene expression changes induced by defeat, and biological pathway analysis
revealed a dominant pattern of down-regulation of myelin-associated genes.
Indeed, 69% of the most significantly down-regulated genes were myelin-related.
The down regulation was confirmed by in situ hybridization histochemistry for two
strongly down-regulated genes, myelin oligodendrocyte glycoprotein (Mog) and
ermin (Ermn), and by immunohistochemistry for myelin basic protein. To test for
stress-induced changes in myelin integrity, aurophosphate (Black Gold) myelin
staining was performed on mPFC sections. Quantitative stereologic analysis showed
reduced myelinated fiber length and density. Behavioral analysis confirmed that
the 14-day social defeat sessions resulted in induction of depressive-like states
measured in social interaction and light/dark tests. The combined data suggest
that chronic social defeat induces molecular changes that reduce myelination of
the prefrontal cortex, which may be an underlying basis for stress-induced
depressive states.
PMID- 28418036
TI - Maximal violation of Bell inequalities under local filtering.
AB - We investigate the behavior of the maximal violations of the CHSH inequality and
Vertesi's inequality under the local filtering operations. An analytical method
has been presented for general two-qubit systems to compute the maximal violation
of the CHSH inequality and the lower bound of the maximal violation of Vertesi's
inequality over the local filtering operations. We show by examples that there
exist quantum states whose non-locality can be revealed after local filtering
operation by the Vertesi's inequality instead of the CHSH inequality.
PMID- 28418037
TI - Mitochondrial C11orf83 is a potent Antiviral Protein Independent of interferon
production.
AB - Mitochondria have a central position in innate immune response via the adaptor
protein MAVS in mitochondrial outer membrane to limit viral replication by
inducing interferon production. Here, we reported that C11orf83, a component of
complex III of electronic transfer chain in mitochondrial inner membrane, was a
potent antiviral protein independent of interferon production. C11orf83
expression significantly increased in response to viral infection, and endows
cells with stronger capability of inhibiting viral replication. Deletion of
C11orf83 permits viral replication easier and cells were more vulnerable to viral
killing. These effects mainly were mediated by triggering OAS3-RNase L system.
C11orf83 overexpression induced higher transcription of OAS3, and knockdown
either OAS3 or RNase L impaired the antiviral capability of C11orf83.
Interestingly, the signaling from C11orf83 to OAS3-RNase L was independent of
interferon production. Thus, our findings suggested a new antiviral mechanism by
bridging cell metabolic machinery component with antiviral effectors.
PMID- 28418039
TI - Solution Process Synthesis of High Aspect Ratio ZnO Nanorods on Electrode Surface
for Sensitive Electrochemical Detection of Uric Acid.
AB - This study demonstrates a highly stable, selective and sensitive uric acid (UA)
biosensor based on high aspect ratio zinc oxide nanorods (ZNRs) vertical grown on
electrode surface via a simple one-step low temperature solution route. Uricase
enzyme was immobilized on the ZNRs followed by Nafion covering to fabricate UA
sensing electrodes (Nafion/Uricase-ZNRs/Ag). The fabricated electrodes showed
enhanced performance with attractive analytical response, such as a high
sensitivity of 239.67 MUA cm-2 mM-1 in wide-linear range (0.01-4.56 mM), rapid
response time (~3 s), low detection limit (5 nM), and low value of apparent
Michaelis-Menten constant (Kmapp, 0.025 mM). In addition, selectivity,
reproducibility and long-term storage stability of biosensor was also
demonstrated. These results can be attributed to the high aspect ratio of
vertically grown ZNRs which provides high surface area leading to enhanced enzyme
immobilization, high electrocatalytic activity, and direct electron transfer
during electrochemical detection of UA. We expect that this biosensor platform
will be advantageous to fabricate ultrasensitive, robust, low-cost sensing device
for numerous analyte detection.
PMID- 28418038
TI - 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF
as an m5C reader.
AB - 5-methylcytosine (m5C) is a post-transcriptional RNA modification identified in
both stable and highly abundant tRNAs and rRNAs, and in mRNAs. However, its
regulatory role in mRNA metabolism is still largely unknown. Here, we reveal that
m5C modification is enriched in CG-rich regions and in regions immediately
downstream of translation initiation sites and has conserved, tissue-specific and
dynamic features across mammalian transcriptomes. Moreover, m5C formation in
mRNAs is mainly catalyzed by the RNA methyltransferase NSUN2, and m5C is
specifically recognized by the mRNA export adaptor ALYREF as shown by in vitro
and in vivo studies. NSUN2 modulates ALYREF's nuclear-cytoplasmic shuttling, RNA
binding affinity and associated mRNA export. Dysregulation of ALYREF-mediated
mRNA export upon NSUN2 depletion could be restored by reconstitution of wild-type
but not methyltransferase-defective NSUN2. Our study provides comprehensive m5C
profiles of mammalian transcriptomes and suggests an essential role for m5C
modification in mRNA export and post-transcriptional regulation.
PMID- 28418040
TI - The Height-Width-Depth Ratios of the Intervertebral Discs and Vertebral Bodies in
Adolescent Idiopathic Scoliosis vs Controls in a Chinese Population.
AB - Adolescent idiopathic scoliosis (AIS) patients have been reported to be taller
and more slender than normal controls, suggesting less mechanical stiffness of
their trunk and spine. For assessment of mechanical stiffness, to our best
knowledge this is the first to study height-width-depth relations at the level of
the individual vertebra and disc in 3-D and to evaluate its relation with the
Cobb angle severity. A unique series of high-resolution pre-operative computed
tomographic (CT) scans of a total of 105 Chinese patients with moderate to severe
AIS and 11 age-matched non-scoliotic controls were used for this study. It was
found that some geometric relations differed between primary thoracic curves,
secondary curves and normal controls at the individual affected vertebra and disc
level. The scoliotic discs in the primary curves were relatively more slender
(taller and thinner) than in secondary curves and as compared to controls. In the
lumbar spinal area, the vertebral bodies were more slender in the primary as well
as secondary AIS curves as compared to the controls. Therefore, if all material
properties remain the same, our finding indicates that scoliotic spines may be
mechanically less stiff than normal spines. No significant correlation between
any of the measures and Cobb angle severity was found.
PMID- 28418041
TI - Highly sensitive strain sensor based on helical structure combined with Mach
Zehnder interferometer in multicore fiber.
AB - Optical fiber sensors for strain measurement have been playing important roles in
structural health monitoring for buildings, tunnels, pipelines, aircrafts, and so
on. A highly sensitive strain sensor based on helical structures (HSs) assisted
Mach-Zehnder interference in an all-solid heterogeneous multicore fiber (MCF) is
proposed and experimentally demonstrated. Due to the HSs, a maximum strain
sensitivity as high as -61.8 pm/MUepsilon was experimentally achieved. This is
the highest sensitivity among interferometer-based strain sensors reported so
far, to the best of our knowledge. Moreover, the proposed sensor has the ability
to discriminate axial strain and temperature, and offers several advantages such
as repeatability of fabrication, robust structure and compact size, which further
benefits its practical sensing applications.
PMID- 28418042
TI - Selective orbital reconstruction in tetragonal FeS: A density functional
dynamical mean-field theory study.
AB - Transport properties of tetragonal iron monosulfide, mackinawite, show a range of
complex features. Semiconductive behavior and proximity to metallic states with
nodal superconductivity mark this d-band system as unconventional quantum
material. Here, we use the density functional dynamical mean-field theory
(DFDMFT) scheme to comprehensively explain why tetragonal FeS shows both
semiconducting and metallic responses in contrast to tetragonal FeSe which is a
pseudogaped metal above the superconducting transition temperature. Within local
density-approximation plus dynamical mean-field theory (LDA+DMFT) we characterize
its paramagnetic insulating and metallic phases, showing the proximity of
mackinawite to selective Mott localization. We report the coexistence of
pseudogaped and anisotropic Dirac-like electronic dispersion at the border of the
Mott transition. These findings announce a new understanding of many-particle
physics in quantum materials with coexisting Dirac-fermions and pseudogaped
electronic states at low energies. Based on our results we propose that in
electron-doped FeS substantial changes would be seen when the metallic regime was
tuned towards an electronic state that hosts unconventional superconductivity.
PMID- 28418044
TI - Design of liquid crystals with 'de Vries-like' properties: structural variants of
carbosilane-terminated 5-phenylpyrimidine mesogens.
AB - Structural variants of the 'de Vries-like' mesogen 5-[4-(12,12,14,14,16,16
hexamethyl-12,14,16-trisilaheptadecyloxy)phenyl]-2-hexyloxypyrimidine (QL16-6),
including two isomers with branched iso-tricarbosilane end-groups, were
synthesized and their mesomorphic and 'de Vries-like' properties were
characterized by polarized optical microscopy, differential scanning calorimetry,
small angle and 2D X-ray scattering techniques. A comparative analysis of isomers
with linear and branched tricarbosilane end-groups shows that they exhibit
comparable mesomorphic and 'de Vries-like' properties. Furthermore, the
difference in effective molecular length Leff between the linear and branched
isomers in the SmA and SmC phases (ca. 4-5 A), which was derived from 2D X-ray
scattering experiments, suggests that the linear tricarbosilane end-group is
hemispherical in shape on the time-average, as predicted by a DFT conformational
analysis at the B3LYP/6-31G* level.
PMID- 28418043
TI - Predicting Protein-protein Association Rates using Coarse-grained Simulation and
Machine Learning.
AB - Protein-protein interactions dominate all major biological processes in living
cells. We have developed a new Monte Carlo-based simulation algorithm to study
the kinetic process of protein association. We tested our method on a previously
used large benchmark set of 49 protein complexes. The predicted rate was
overestimated in the benchmark test compared to the experimental results for a
group of protein complexes. We hypothesized that this resulted from molecular
flexibility at the interface regions of the interacting proteins. After applying
a machine learning algorithm with input variables that accounted for both the
conformational flexibility and the energetic factor of binding, we successfully
identified most of the protein complexes with overestimated association rates and
improved our final prediction by using a cross-validation test. This method was
then applied to a new independent test set and resulted in a similar prediction
accuracy to that obtained using the training set. It has been thought that
diffusion-limited protein association is dominated by long-range interactions.
Our results provide strong evidence that the conformational flexibility also
plays an important role in regulating protein association. Our studies provide
new insights into the mechanism of protein association and offer a
computationally efficient tool for predicting its rate.
PMID- 28418045
TI - Correction: A molecular dynamics study of the ionic liquid, choline acetate.
AB - Correction for 'A molecular dynamics study of the ionic liquid, choline acetate'
by Jon A. L. Willcox et al., Phys. Chem. Chem. Phys., 2016, 18, 14850-14858.
PMID- 28418046
TI - Novel nickel(ii) complexes of sterically modified linear N4 ligands: effect of
ligand stereoelectronic factors and solvent of coordination on nickel(ii) spin
state and catalytic alkane hydroxylation.
AB - A series of Ni(ii) complexes of the types [Ni(L)(CH3CN)2](BPh4)21-3, 5 and
[Ni(L4)](BPh4)24, where L = N,N'-bis(2-pyrid-2-ylmethyl)-1,4-diazepane (L1), N-(6
methylpyrid-2-ylmethyl)-N'-(pyrid-2-ylmethyl)-1,4-diazepane (L2), N,N'-bis(6
methyl-2-pyridylmethyl)-1,4-diazepane (L3), N,N'-dimethyl-N,N'-bis(2
pyridylmethyl)ethylenediamine (L5) and L4 = N,N'-bis((1-methyl-1H-imidazole-2
yl)methyl)-1,4-diazepane, have been isolated and characterized. The complex
cations of 1 and 4 possess, respectively, distorted octahedral and low-spin
square planar coordination geometries in which nickel(ii) is meridionally
coordinated to all four nitrogen atoms of L1 and L4. DFT studies reveal that L5
with the ethylenediamine backbone coordinates in the cis-beta mode in
[Ni(L5)(CH3CN)2]2+5, but in the cis-alpha mode in [Ni(L5)(H2O)2]2+. Also, they
illustrate the role of ligand donor atom type, diazacyclo backbone and steric
hindrance to coordination of pyridyl nitrogen in conferring novel coordination
geometries on Ni(ii). All these complexes catalyse the oxidation of cyclohexane
in the presence of m-CPBA as the oxidant up to 600 turnover numbers (TON) with
relatively good alcohol selectivity (A/K, 5.6-7.2). Adamantane is oxidized to 1
adamantanol, 2-adamantanol and 2-adamantanone with high bond selectivity (3
degrees /2 degrees , 8.7-11.7). The incorporation of methyl substituent(s) on one
(2) or both (3) of the pyridyl rings and the replacement of both the
pyridylmethyl arms in 1 by imidazolylmethyl arms to give 4 decrease the catalytic
efficiency. Interestingly, 5 with the cis-beta mode of coordination provides two
labile cis coordination sites for oxidant binding, leading to higher total TON
and product/bond selectivity.
PMID- 28418047
TI - An FTIR emission study of the products of NO A2Sigma+ (v = 0, 1) + O2 collisions.
AB - Collisional quenching of NO A2Sigma+ (v = 0, 1) by O2 has been studied through
the detection of vibrationally excited products by time-resolved Fourier
transform infrared emission spectroscopy. Non-reactive quenching of NO A2Sigma+
(v = 0) produces a vibrational distribution in NO X2Pi which has been quantified
for v = 2-22, and is found to be bimodal. The results are consistent with two
quenching channels. The first forms the ground X3Sigma or low-lying a 1Deltag
electronic state of O2 with a distribution including high vibrational levels of
NO X2Pi which is slightly hotter than statistical. Two possibilities are
identified for the second channel. The first, with a similar quantum yield to
that producing higher vibrational levels, forms a highly electronically excited
state, such as O2 c1Sigma, with low vibrational levels in NO X2Pi which are
inverted with a distribution resembling that resulting from a sudden or harpoon
mechanism. The second is that ground state oxygen is formed with low vibrational
energy partitioned into NO X2Pi. In addition, vibrationally excited NO2 is
observed, but at intensities which indicate that it is formed in low quantum
yield. Quantitatively unobservable processes (defined as those which do not form
ground state NO (v >= 2)) are found to have a branching ratio of at most 25 +/-
5%. The results are compared with those of previous studies and the most
consistent interpretation suggests that dissociation of O2 to form ground state
O(3P) atoms and ground vibrational state NO X2Pi (v = 0) is the main reactive
process rather than NO2 formation. Qualitatively similar results are seen for the
quenching of NO A2Sigma+ (v = 1).
PMID- 28418048
TI - DNA-spheres decorated with magnetic nanocomposites based on terminal transfer
reactions for versatile target detection and cellular targeted drug delivery.
AB - We present an elegant approach to make a magnetic nanoparticle (MNP) conjugated
DNA-sphere (MNP/DNA-SP) which is integrated with disulfide (MNP/DS-SP) or an
aptamer (MNP/sgc8-SP) for GSH detection, selective cancer cell recognition,
effective drug delivery, and bioimaging.
PMID- 28418049
TI - Systems chemistry.
AB - Building on our ability to design and synthesise molecules and our understanding
of the noncovalent interactions between these molecules, the chemical sciences
are currently entering the new territory of Systems Chemistry. This young field
aims to develop complex molecular systems showing emergent properties; i.e.
properties that go beyond the sum of the characteristics of the individual
consituents of the system. This review gives an impression of the state of the
art of the field by showing a diverse number of recent highlights, including out
of-equilibrium self-assembly, chemically fuelled molecular motion,
compartmentalised chemical networks and designed oscillators. Subsequently a
number of current challenges related to the design of complex chemical systems
are discussed, including those of creating concurrent formation-destruction
systems, continuously maintaining chemical systems away from equilibrium,
incorporating feedback loops and pushing replication chemistry away from
equilibrium. Finally, the prospects for Systems Chemistry are discussed including
the tantalizing vision of the de novo synthesis of life and the idea of self
synthesising and self-repairing chemical factories.
PMID- 28418051
TI - A structural bioinformatics investigation on protein-DNA complexes delineates
their modes of interaction.
AB - The lifetimes of protein-DNA adducts are strictly related to the various protein
functions. This feature must be encoded by the amino acids located at the protein
DNA interface. The large number of structurally characterized protein-DNA
complexes now available from the Protein Data Bank (PDB) allows extensive
structural bioinformatics investigations on protein-DNA interfaces. The modes of
protein binding to DNA have been explored by dividing 629 non-redundant PDB files
of protein-DNA complexes into separate classes for structural proteins,
transcription factors and DNA-related enzymes. From the selected PDB structures,
we could define 2953 protein-DNA contact regions. A systematic analysis of amino
acid occurrences at these protein-DNA contact regions yielded composition
profiles, which are typical for each of the three protein classes. The critical
role of some amino acids to influence intermolecular contact lifetimes is
discussed here. The occurrence of arginine at the protein-DNA interface, by far
the most abundant amino acid in this protein moiety, is found to be the main
feature that differentiates proteins from the three classes. Structural proteins
and, to a lesser extent, transcription factors exhibit the highest Arg occurrence
at protein-DNA contact regions. Reduced Arg/Lys ratios together with increased
contents of Asp and Glu are observed in all the DNA-interacting enzymes. The
amount of negatively charged side chains, highly conserved among homologous DNA
related enzymes at protein-DNA interfaces, is suggested as a tool to modulate
protein mobility along DNA chains. Arg/Lys, Asp/Asn and Glu/Gln substitutions at
protein-DNA interfaces may represent a very feasible way to control protein
motion on DNA rails.
PMID- 28418050
TI - Reversible helical chirality of perylene bisimide aggregates: amino acid-directed
chiral transfer and chiral inversion.
AB - Through the formation of dynamic covalent bonds, we succeeded, for the first
time, in achieving a reversible chiral transfer from amino acids to perylene
bisimide aggregates in aqueous solutions. Two opposite helical aggregations are
induced with l-phenylalanine and l-tyrosine, respectively. It is possible that
the change in configurations of phenyl groups in amino acids leads to the chiral
inversion of BAPBI arrangements.
PMID- 28418052
TI - Thermal spin-crossover with a large hysteresis spanning room temperature in a
mononuclear complex.
AB - A large hysteresis centered around room temperature represents one of the
mandatory goals of research on functional switchable materials. In the thoroughly
studied field of spin-crossover, such behaviour appears very rarely and
essentially concerns coordination networks. A new compound showing a large spin
crossover hysteresis spanning room temperature demonstrates in a definitive
manner that this goal is achievable in molecular discrete compounds without
damaging the single-crystal character.
PMID- 28418053
TI - A new route for the preparation of enriched iso-polylactide from rac-lactide via
a Lewis acid catalyzed ring-opening of an epoxide.
AB - Tetraphenylporphyrin aluminum(iii) salts, TPPAlX, where X = Me, OEt, OiPr,
OCHMeCH2Cl, and Cl, and bis(triphenylphosphine)imminium chloride, PPN+Cl- (1 : 1)
react with rac-lactide, rac-LA, in neat propylene oxide, PO, to yield chains of
enriched isotactic polylactide, PLA, with end groups of PO-Cl and with time these
yield cyclic polymers (PO)n(PLA) where n = 2 or 3 and even higher. There is no
reaction between TPPAlOR (R = Et or iPr), PPN+Cl-, and rac-LA in neat THF at 25
degrees C even though TPPAlOR (R = Et or iPr) and PPN+Cl- in neat PO yields
polypropylene oxide with a terminal OR group, H(PO)nOR. Taken together, Al(iii)
acts as a Lewis acid in the ring-opening of PO, in which PPN+Cl- is present and
the incipient ClCH2CHMeO- initiates the ROP of LA to yield anion chains of [(PLA)
OCHMeCH2Cl]-, and then the ring-opening of PO yields cycles, (PO)n(PLA), with the
liberation of Cl-. The polymer was isolated by the addition of MeOH/HCl and end
group analysis by mass spectrometry.
PMID- 28418054
TI - Addressing uncertainty in atomistic machine learning.
AB - Machine-learning regression has been demonstrated to precisely emulate the
potential energy and forces that are output from more expensive electronic
structure calculations. However, to predict new regions of the potential energy
surface, an assessment must be made of the credibility of the predictions. In
this perspective, we address the types of errors that might arise in atomistic
machine learning, the unique aspects of atomistic simulations that make machine
learning challenging, and highlight how uncertainty analysis can be used to
assess the validity of machine-learning predictions. We suggest this will allow
researchers to more fully use machine learning for the routine acceleration of
large, high-accuracy, or extended-time simulations. In our demonstrations, we use
a bootstrap ensemble of neural network-based calculators, and show that the width
of the ensemble can provide an estimate of the uncertainty when the width is
comparable to that in the training data. Intriguingly, we also show that the
uncertainty can be localized to specific atoms in the simulation, which may offer
hints for the generation of training data to strategically improve the machine
learned representation.
PMID- 28418055
TI - Application of machine/statistical learning, artificial intelligence and
statistical experimental design for the modeling and optimization of methylene
blue and Cd(ii) removal from a binary aqueous solution by natural walnut carbon.
AB - Analytical chemists apply statistical methods for both the validation and
prediction of proposed models. Methods are required that are adequate for finding
the typical features of a dataset, such as nonlinearities and interactions.
Boosted regression trees (BRTs), as an ensemble technique, are fundamentally
different to other conventional techniques, with the aim to fit a single
parsimonious model. In this work, BRT, artificial neural network (ANN) and
response surface methodology (RSM) models have been used for the optimization
and/or modeling of the stirring time (min), pH, adsorbent mass (mg) and
concentrations of MB and Cd2+ ions (mg L-1) in order to develop respective
predictive equations for simulation of the efficiency of MB and Cd2+ adsorption
based on the experimental data set. Activated carbon, as an adsorbent, was
synthesized from walnut wood waste which is abundant, non-toxic, cheap and
locally available. This adsorbent was characterized using different techniques
such as FT-IR, BET, SEM, point of zero charge (pHpzc) and also the determination
of oxygen containing functional groups. The influence of various parameters (i.e.
pH, stirring time, adsorbent mass and concentrations of MB and Cd2+ ions) on the
percentage removal was calculated by investigation of sensitive function,
variable importance rankings (BRT) and analysis of variance (RSM). Furthermore, a
central composite design (CCD) combined with a desirability function approach
(DFA) as a global optimization technique was used for the simultaneous
optimization of the effective parameters. The applicability of the BRT, ANN and
RSM models for the description of experimental data was examined using four
statistical criteria (absolute average deviation (AAD), mean absolute error
(MAE), root mean square error (RMSE) and coefficient of determination (R2)). All
three models demonstrated good predictions in this study. The BRT model was more
precise compared to the other models and this showed that BRT could be a powerful
tool for the modeling and optimizing of removal of MB and Cd(ii). Sensitivity
analysis (calculated from the weight of neurons in ANN) confirmed that the
adsorbent mass and pH were the essential factors affecting the removal of MB and
Cd(ii), with relative importances of 28.82% and 38.34%, respectively. A good
agreement (R2 > 0.960) between the predicted and experimental values was
obtained. Maximum removal (R% > 99) was achieved at an initial dye concentration
of 15 mg L-1, a Cd2+ concentration of 20 mg L-1, a pH of 5.2, an adsorbent mass
of 0.55 g and a time of 35 min.
PMID- 28418056
TI - Unprecedented thermal condensation of tetracyanocyclopropanes to
triazaphenalenes: a facile route for the design of novel materials for electronic
applications.
AB - We report an unusual thermal condensation of readily available
tetracyanocyclopropanes to tetracyanosubstituted triazaphenalenes, which revealed
interesting optoelectronic properties such as strongly pronounced solvatochromism
and bright photoluminescence. Optical memory elements and organic light emitting
diodes with a deep red electroluminescence were designed using triazaphenalenes,
thus highlighting the potential of these compounds as materials for electronic
applications.
PMID- 28418057
TI - Geometry-dependent compressive responses in nanoimprinted submicron-structured
shape memory polyurethane.
AB - High resolution surface textures, when rationally designed, provide an attractive
surface engineering approach to enhance surface functionalities. Designing smart
surfaces by coupling surface texture with shape memory polymers has garnered
attention in achieving tunable mechanical properties. We investigate the
structure-mechanical property relationships for programmable, shape-memorizing
submicron-scale pillar arrays subjected to flat-punch compression. The
geometrically-dependent deformation of structured surfaces with two different
aspect ratios (250 nm-pillars 1 : 1 and 550 nm-pillars 2.4 : 1) were
investigated, and their moduli were found to be lower than that of non-patterned
surface. From finite element analysis, the pillar deformation is correlated to a
mechanistic transition from a discrete, unidirectional compression of 250 nm
pillars to lateral constraints caused by interpillar contact in 550 nm-pillars.
This lateral pillar-pillar contact in the 550 nm-pillars resulted in an increased
and maximum strain-dependent modulus but lower elastic recovery and energy
dissipation as compared with the 250 nm-pillars. Furthermore, the compressive
responses of temporarily shaped pillars (programmed by stretching) were compared
with the permanently shaped pillars. The extent of lateral constraints controlled
by pillar shape and spacing in 550 nm-pillars was responsible for the modulus
differences between the original and stretched patterns, whereas the modulus of
250 nm-pillars remained as a constant value with different levels of stretching.
This study provides mechanistic insights into how the mechanical behavior can be
modulated by designing the aspect ratio of shape memory pillar arrays and by
programming the surface geometry, thus revealing the potential of developing
ingenious designs of responsive surfaces sensitive to mechanical deformation.
PMID- 28418058
TI - Crystalline nanotubular framework constructed by cucurbit[8]uril for selective
CO2 adsorption.
AB - A crystalline nanotubular framework was constructed by cucurbit[8]uril (CB[8])
molecules in the presence of a molecular chaperone. Compared with amorphous
CB[8], the framework exhibits highly selective adsorption for CO2 over N2, CH4,
and H2.
PMID- 28418059
TI - Hybrid micro-/nano-structures derived from metal-organic frameworks: preparation
and applications in energy storage and conversion.
AB - Metal-organic frameworks (MOFs), an important class of inorganic-organic hybrid
crystals with intrinsic porous structures, can be used as versatile precursors or
sacrificial templates for preparation of numerous functional nanomaterials for
various applications. Recent developments of MOF-derived hybrid micro-/nano
structures, constructed by more than two components with varied functionalities,
have revealed their extensive capabilities to overcome the weaknesses of the
individual counterparts and thus give enhanced performance for energy storage and
conversion. In this tutorial review, we summarize the recent advances in MOF
derived hybrid micro-/nano-structures. The synthetic strategies for preparing MOF
derived hybrid micro-/nano-structures are first introduced. Focusing on energy
storage and conversion, we then discuss their potential applications in lithium
ion batteries, lithium-sulfur batteries, supercapacitors, lithium-oxygen
batteries and fuel cells. Finally, we give our personal insights into the
challenges and opportunities for the future research of MOF-derived hybrid micro
/nano-structures.
PMID- 28418060
TI - Reaction chemistry in rechargeable Li-O2 batteries.
AB - The seemingly simple reaction of Li-O2 batteries involving lithium and oxygen
makes this chemistry attractive for high-energy-density storage systems; however,
achieving this reaction in practical rechargeable Li-O2 batteries has proven
difficult. The reaction paths leading to the final Li2O2 discharge products can
be greatly affected by the operating conditions or environment, which often
results in major side reactions. Recent research findings have begun to reveal
how the reaction paths may be affected by the surrounding conditions and to
uncover the factors contributing to the difficulty in achieving the reactions of
lithium and oxygen. This progress report describes the current state of
understanding of the electrode reaction mechanisms in Li-O2 batteries; the
factors that affect reaction pathways; and the effect of cell components such as
solvents, salts, additives, and catalysts on the discharge product and its
decomposition during charging. This comprehensive review of the recent progress
in understanding the reaction chemistry of the Li-O2 system will serve as
guidelines for future research and aid in the development of reliable high-energy
density rechargeable Li-O2 batteries.
PMID- 28418061
TI - Self-powered electrochemical systems as neurochemical sensors: toward self
triggered in vivo analysis of brain chemistry.
AB - Real-time in vivo analysis of neurochemical dynamics has great physiological and
pathological implications for a full understanding of the brain. Self-powered
electrochemical systems (SPESs) built on galvanic cell configurations bear the
advantages of easy miniaturization for implantation and no interference to
electric activities of neurons over traditional externally-powered
electrochemical sensors for self-triggered in vivo analysis. However, this is
still a new concept for in vivo neurochemical sensing with few implanted examples
reported so far. This tutorial review summarizes the development of SPESs toward
implantable applications from both principal and practical perspectives,
ultimately aimed at providing a guide map to the future design of neurochemical
sensors for in vivo analysis of brain chemistry.
PMID- 28418062
TI - Flexible aspartates propel iron to the ferroxidation sites along pathways
stabilized by a conserved arginine in Dps proteins from Mycobacterium smegmatis.
AB - DNA-binding proteins under starvation (Dps) are dodecameric nano-compartments for
iron oxidation and storage in bacterial cells. These proteins have roughly
spherical structures with a hollow interior where iron is stored. Through
mutational analysis of a conserved arginine residue in the second Dps protein
from Mycobacterium smegmatis, we have identified residues which stabilize the
interfaces between the iron entry and ferroxidation sites. Also, we have used X
ray crystallography to determine the structures of co-crystals of iron and Dps in
varying proportions and compare the changes in these ligand-bound forms with
respect to the apo-protein. The iron-loaded proteins of low, medium and high iron
bound forms were found to exhibit aspartate residues with alternate
conformations, some of which could be directly linked to the sites of
ferroxidation and iron entry. We conclude that the increased flexibility of
aspartates in the presence of iron facilitates its movement from the entry site
to the ferroxidaton site, and the two active sites are stabilized by the
interactions of a conserved arginine residue R73.
PMID- 28418063
TI - Ab initio modelling of oxygen vacancy arrangement in highly defective HfO2
resistive layers.
AB - We report ab initio results for sub-stoichiometric HfOx with different oxygen
vacancy densities, useful in exploring microscopic mechanisms that govern the
operation of RRAM devices. We demonstrate that oxygen vacancy filaments are
energetically more stable than randomly distributed defects. Furthermore, the
stability of the filaments increases with the number of confined oxygen
vacancies. Energetic and structural analyses show that bonds between neighboring
coordinative unsaturated Hf atoms promote filament stability, and electron
trapping, due to electron injection, increases the cohesive energy until the
injection is moderate. The highly oxygen deficient configuration of the filaments
leads to a substantial lowering of the HfOx band gap, which locally increases the
conductivity of the system. Charge injection and electric fields modify the
mobility of oxygen ions in the proximity of the filament. The simulations suggest
that oxygen ion diffusion can lead to an asymmetric reduction of filament
thickness and thus to its progressive disruption where the vacancy cohesion
energy is lower.
PMID- 28418064
TI - Surfactant exfoliated 2D hexagonal Boron Nitride (2D-hBN) explored as a potential
electrochemical sensor for dopamine: surfactants significantly influence sensor
capabilities.
AB - Surfactant exfoliated 2D hexagonal Boron Nitride (2D-hBN) nanosheets are explored
as a potential electrochemical sensing platform and evaluated towards the
electroanalytical sensing of dopamine (DA) in the presence of the common
interferents, ascorbic acid (AA) and uric acid (UA). Surfactant exfoliated 2D-hBN
nanosheets (2-4 layers) fabricated using sodium cholate in aqueous media are
electrically wired via a drop-casting modification process onto disposable screen
printed graphite electrodes (SPEs). We critically evaluate the performance of
these 2D-hBN modified SPEs and demonstrate the effect of 'mass coverage' towards
the detection of DA, AA and UA. Previous studies utilising surfactant-free
(pristine) 2D-hBN modified SPEs have shown a beneficial effect towards the
detection of DA, AA and UA when compared to the underlying/unmodified graphite
based electrode. We show that the fabrication route utilised to prepare 2D-hBN is
a vital experimental consideration, such that the beneficial effect previously
reported is considerably reduced when surfactant exfoliated 2D-hBN is utilised.
We demonstrate for the first time, through implementation of control experiments
in the form of surfactant modified graphite electrodes, that sodium cholate is a
major contributing factor to the aforementioned detrimental behaviour. The
significance here is not in the material per se, but the fundamental knowledge of
the surfactant and surface coverage changing the electrochemical properties of
the material under investigation. Given the wide variety of ionic and non-ionic
surfactants that are utilised in the manufacture of novel 2D materials, the
control experiments reported herein need to be performed in order to de-convolute
the electrochemical response and effectively evaluate the 'underlying
surface/surfactant/2D materials' electrocatalytic contribution.
PMID- 28418065
TI - Vitamin E for Alzheimer's dementia and mild cognitive impairment.
AB - BACKGROUND: Vitamin E occurs naturally in the diet. It has several biological
activities, including functioning as an antioxidant to scavenge toxic free
radicals. Evidence that free radicals may contribute to the pathological
processes behind cognitive impairment has led to interest in the use of vitamin E
supplements to treat mild cognitive impairment (MCI) and Alzheimer's disease
(AD). This is an update of a Cochrane Review first published in 2000, and
previously updated in 2006 and 2012. OBJECTIVES: To assess the efficacy of
vitamin E in the treatment of MCI and dementia due to AD. SEARCH METHODS: We
searched the Specialized Register of the Cochrane Dementia and Cognitive
Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO,
CINAHL, LILACS as well as many trials databases and grey literature sources on 22
April 2016 using the terms: "Vitamin E", vitamin-E, alpha-tocopherol. SELECTION
CRITERIA: We included all double-blind, randomised trials in which treatment with
any dose of vitamin E was compared with placebo in people with AD or MCI. DATA
COLLECTION AND ANALYSIS: We used standard methodological procedures according to
the Cochrane Handbook for Systematic Reviews of Interventions. We rated the
quality of the evidence using the GRADE approach. Where appropriate we attempted
to contact authors to obtain missing information. MAIN RESULTS: Four trials met
the inclusion criteria, but we could only extract outcome data in accordance with
our protocol from two trials, one in an AD population (n = 304) and one in an MCI
population (n = 516). Both trials had an overall low to unclear risk of bias. It
was not possible to pool data across studies owing to a lack of comparable
outcome measures.In people with AD, we found no evidence of any clinically
important effect of vitamin E on cognition, measured with change from baseline in
the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) over six
to 48 months (mean difference (MD) -1.81, 95% confidence interval (CI) -3.75 to
0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no
evidence of a difference between vitamin E and placebo groups in the risk of
experiencing at least one serious adverse event over six to 48 months (risk ratio
(RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality
evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1
study, n = 304; moderate quality evidence). People with AD receiving vitamin E
showed less functional decline on the Alzheimer's Disease Cooperative
Study/Activities of Daily Living Inventory than people receiving placebo at six
to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study,
n = 280; moderate quality evidence). There was no evidence of any clinically
important effect on neuropsychiatric symptoms measured with the Neuropsychiatric
Inventory (MD -1.47, 95% CI -4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate
quality evidence).We found no evidence that vitamin E affected the probability of
progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95%
CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five
deaths occurred in each of the vitamin E and placebo groups over the 36 months
(RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality
evidence). We were unable to extract data in accordance with the review protocol
for other outcomes. However, the study authors found no evidence that vitamin E
differed from placebo in its effect on cognitive function, global severity or
activities of daily living . There was also no evidence of a difference between
groups in the more commonly reported adverse events. AUTHORS' CONCLUSIONS: We
found no evidence that the alpha-tocopherol form of vitamin E given to people
with MCI prevents progression to dementia, or that it improves cognitive function
in people with MCI or dementia due to AD. However, there is moderate quality
evidence from a single study that it may slow functional decline in AD. Vitamin E
was not associated with an increased risk of serious adverse events or mortality
in the trials in this review. These conclusions have changed since the previous
update, however they are still based on small numbers of trials and participants
and further research is quite likely to affect the results.
PMID- 28418066
TI - A National Survey on the Effect of the Geriatric Academic Career Award in
Advancing Academic Geriatric Medicine.
AB - A workforce that understands principles of geriatric medicine is critical to
addressing the care needs of the growing elderly population. This will be
impossible without a substantial increase in academicians engaged in education
and aging research. Limited support of early-career clinician-educators is a
major barrier to attaining this goal. The Geriatric Academic Career Award (GACA)
was a vital resource that benefitted 222 junior faculty members. GACA
availability was interrupted in 2006, followed by permanent discontinuation after
the Geriatrics Workforce Education Program (GWEP) subsumed it in 2015, leaving
aspiring clinician-educators with no similar alternatives. GACA recipients were
surveyed in this cross-sectional, multimethod study to assess the effect of the
award on career development, creation and dissemination of educational products,
funding discontinuation consequences, and implications of program closure for the
future of geriatric health care. Uninterrupted funding resulted in fulfillment of
GACA goals (94%) and overall career success (96%). Collectively, awardees reached
more than 40,700 learners. Funding interruption led to 55% working additional
hours over and above an increased clinical workload to continue their GACA
related research and scholarship. Others terminated GACA projects (36%) or
abandoned academic medicine altogether. Of respondents currently at GWEP sites
(43%), only 13% report a GWEP budget including GACA-like support. Those with GWEP
roles attributed their current standing to experience gained through GACA
funding. These consequences are alarming and represent a major setback to
academic geriatrics. GACA's singular contribution to the mission of geriatric
medicine must prompt vigorous efforts to restore it as a distinct funding
opportunity.
PMID- 28418067
TI - A case series of vital signs-controlled, patient-assisted intravenous analgesia
(VPIA) using remifentanil for labour and delivery.
AB - Intravenous remifentanil patient-controlled analgesia can be used during labour
as an alternative to epidural analgesia. Adverse effects of opioids, including
hypoxia and bradycardia, may lead to maternal morbidity and mortality. We devised
an interactive feedback system based on a clinical proportional algorithm, to
continuously monitor for adverse effects to enhance safety and better titrate
analgesia. This vital signs-controlled, patient-assisted intravenous analgesia
with remifentanil used a prototype delivery system linked to a pulse oximeter
that evaluated maternal oxygen saturation and heart rate continuously. With this
system, we detected oxygen saturation < 95% for more than 60 s in 15 of 29
subjects (52%); and heart rate < 60 min-1 for more than 60 s in 7 of 29 subjects
(24%) during use. The system automatically responded appropriately by reducing
the dosages and temporarily halting remifentanil administration, thus averting
further hypoxia and bradycardia.
PMID- 28418068
TI - Recombinant overexpression of dihydroneopterin aldolase catalyst potentially
regulates folate-biofortification.
AB - We aim to investigate the prospects of increased production of folate through the
overexpression of heterologous dihydroneopterin aldolase catalyst. The gene
encoding aldolase catalyst was cloned into an expression vector and the induced
recombinant protein was purified through metal-affinity chromatography which
appeared at 14 kDa position on polyacrylamide-gel. Remarkably, a periodic
increase in the extracellular and intracellular folic acid concentration was
observed at 4 h growth of induced recombinant DHNA samples than control in a pH
dependent manner. Maximum folate concentration was observed with at least twofold
increase in induced recombinant samples at pH8.0 compared to the significant
decline at 6 h growth. Consistently, heterologous overexpression of bacterial
aldolase through Agrobacterium-mediated genetic transformation of tobacco led to
more than 2.5-fold increase in the folate concentration in the transgenic leaves
than control tissues. These data are veritable inspecting metabolic flux in both
bacterial and plant systems, thus providing directions for future research on
folate agri-fortification.
PMID- 28418069
TI - Genetic control of plasticity of oil yield for combined abiotic stresses using a
joint approach of crop modelling and genome-wide association.
AB - Understanding the genetic basis of phenotypic plasticity is crucial for
predicting and managing climate change effects on wild plants and crops. Here, we
combined crop modelling and quantitative genetics to study the genetic control of
oil yield plasticity for multiple abiotic stresses in sunflower. First, we
developed stress indicators to characterize 14 environments for three abiotic
stresses (cold, drought and nitrogen) using the SUNFLO crop model and phenotypic
variations of three commercial varieties. The computed plant stress indicators
better explain yield variation than descriptors at the climatic or crop levels.
In those environments, we observed oil yield of 317 sunflower hybrids and
regressed it with three selected stress indicators. The slopes of cold stress
norm reaction were used as plasticity phenotypes in the following genome-wide
association study. Among the 65 534 tested Single Nucleotide Polymorphisms
(SNPs), we identified nine quantitative trait loci controlling oil yield
plasticity to cold stress. Associated single nucleotide polymorphisms are
localized in genes previously shown to be involved in cold stress responses:
oligopeptide transporters, lipid transfer protein, cystatin, alternative oxidase
or root development. This novel approach opens new perspectives to identify
genomic regions involved in genotype-by-environment interaction of a complex
traits to multiple stresses in realistic natural or agronomical conditions.
PMID- 28418070
TI - A signature of tree health? Shifts in the microbiome and the ecological drivers
of horse chestnut bleeding canker disease.
AB - Host susceptibility to pathogens can be shaped by genetic, ecological, and
evolutionary factors. The ability to predict the spread of disease therefore
requires an integrated understanding of these factors, including effects of pests
on pathogen growth and competition between pathogens and commensal microbiota for
host resources. We examined interactions between the leaf-mining moth Cameraria
ohridella, the bacterial causal agent of bleeding canker disease Pseudomonas
syringae pv aesculi, and the bark-associated microbiota of horse chestnut
(Aesculus hippocastanum) trees. Through surveys of > 900 trees from 60 sites in
the UK, we tested for ecological or life history predictors of leaf miner
infestation, bleeding canker, or coinfection. Using culture-independent
sequencing, we then compared the bark microbiomes from 46 trees to measure the
association between microbiome composition and key ecological variables,
including the severity of disease. Both pest and pathogen were found to respond
to tree characteristics, but neither explained damage inflicted by the other.
However, we found a clear loss of microbial diversity and associated shift in
microbiome composition of trees as a function of disease. These results show a
link between bark-associated microbiota and tree health that introduces the
intriguing possibility that tree microbiota play key roles in the spread of
disease.
PMID- 28418071
TI - Chronic exposure to graphene-based nanomaterials induces behavioral deficits and
neural damage in Caenorhabditis elegans.
AB - Nanomaterials of graphene and its derivatives have been widely applied in recent
years, but whose impacts on the environment and health are still not well
understood. In the present study, the potential adverse effects of graphite (G),
graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor
nervous system were investigated using nematode Caenorhabditis elegans as the
assay system. After being characterized using TEM, SEM, XPS and PLE, three
nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100
mg l-1 GO caused a significant reduction in the survival rate, but G and GDDs
showed low lethality on nematodes. After chronic exposure of sub-lethal dosages,
three nanomaterials were observed to distribute primarily in the pharynx and
intestine; but GQDs were widespread in nematode body. Three graphene-based
nanomaterials resulted in significant declines in locomotor frequency of body
bending, head thrashing and pharynx pumping. In addition, mean speed, bending
angle-frequency and wavelength of the crawling movement were significantly
reduced after exposure. Using transgenic nematodes, we found high concentrations
of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat
4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene
based nanomaterials can lead to damages in the dopaminergic and glutamatergic
neurons. The present data suggest that chronic exposure of graphene-based
nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and
neural damage. These findings provide useful information to understand the
toxicity and safe application of graphene-based nanomaterials. Copyright (c) 2017
John Wiley & Sons, Ltd.
PMID- 28418072
TI - MYB-GATA1 fusion promotes basophilic leukaemia: involvement of interleukin-33 and
nerve growth factor receptors.
AB - Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloblastic
leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation
generating an MYB-GATA1 fusion gene in male infants with ABL. To better
understand its role, the chimeric MYB-GATA1 transcription factor was expressed in
CD34-positive haematopoietic progenitors, which were transplanted into
immunodeficient mice. Cells expressing MYB-GATA1 showed increased expression of
markers of immaturity (CD34), of granulocytic lineage (CD33 and CD117), and of
basophilic differentiation (CD203c and FcepsilonRI). UT-7 cells also showed
basophilic differentiation after MYB-GATA1 transfection. A transcriptomic study
identified nine genes deregulated by both MYB-GATA1 and basophilic
differentiation. Induction of three of these genes (CCL23, IL1RL1, and NTRK1) was
confirmed in MYB-GATA1-expressing CD34-positive cells by reverse transcription
quantitative polymerase chain reaction. Interleukin (IL)-33 and nerve growth
factor (NGF), the ligands of IL-1 receptor-like 1 (IL1RL1) and neurotrophic
receptor tyrosine kinase 1 (NTRK1), respectively, enhanced the basophilic
differentiation of MYB-GATA1-expressing UT-7 cells, thus demonstrating the
importance of this pathway in the basophilic differentiation of leukaemic cells
and CD34-positive primary cells. Finally, gene reporter assays confirmed that MYB
and MYB-GATA1 directly activated NTRK1 and IL1RL1 transcription, leading to
basophilic skewing of the blasts. MYB-GATA1 is more efficient than MYB, because
of better stability. Our results highlight the role of IL-33 and NGF receptors in
the basophilic differentiation of normal and leukaemic cells. Copyright (c) 2017
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28418073
TI - Evolved changes in the intracellular distribution and physiology of muscle
mitochondria in high-altitude native deer mice.
AB - KEY POINTS: Mitochondrial function changes over time at high altitudes, but the
potential benefits of these changes for hypoxia resistance remains unclear. We
used high-altitude-adapted populations of deer mice, which exhibit enhanced
aerobic performance in hypoxia, to examine whether changes in mitochondrial
physiology or intracellular distribution in the muscle contribute to hypoxia
resistance. Permeabilized muscle fibres from the gastrocnemius muscle had higher
respiratory capacities in high-altitude mice than in low-altitude mice.
Highlanders also had higher mitochondrial volume densities, due entirely to an
enriched abundance of subsarcolemmal mitochondria, such that more mitochondria
were situated near the cell membrane and adjacent to capillaries. There were
several effects of hypoxia acclimation on mitochondrial function, some of which
were population specific, but they differed from the evolved changes in high
altitude natives, which probably provide a better indication of adaptive traits
that improve performance and hypoxia resistance at high altitudes. ABSTRACT: High
altitude natives that have evolved to live in hypoxic environments provide a
compelling system to understand how animals can overcome impairments in oxygen
availability. We examined whether these include changes in mitochondrial
physiology or intracellular distribution that contribute to hypoxia resistance in
high-altitude deer mice (Peromyscus maniculatus). Mice from populations native to
high and low altitudes were born and raised in captivity, and as adults were
acclimated to normoxia or hypobaric hypoxia (equivalent to 4300 m elevation). We
found that highlanders had higher respiratory capacities in the gastrocnemius
(but not soleus) muscle than lowlanders (assessed using permeabilized fibres with
single or multiple inputs to the electron transport system), due in large part to
higher mitochondrial volume densities in the gastrocnemius. The latter was
attributed to an increased abundance of subsarcolemmal (but not
intermyofibrillar) mitochondria, such that more mitochondria were situated near
the cell membrane and adjacent to capillaries. Hypoxia acclimation had no
significant effect on these population differences, but it did increase
mitochondrial cristae surface densities of mitochondria in both populations.
Hypoxia acclimation also altered the physiology of isolated mitochondria by
affecting respiratory capacities and cytochrome c oxidase activities in
population-specific manners. Chronic hypoxia decreased the release of reactive
oxygen species by isolated mitochondria in both populations. There were subtle
differences in O2 kinetics between populations, with highlanders exhibiting
increased mitochondrial O2 affinity or catalytic efficiency in some conditions.
Our results suggest that evolved changes in mitochondrial physiology in high
altitude natives are distinct from the effects of hypoxia acclimation, and
probably provide a better indication of adaptive traits that improve performance
and hypoxia resistance at high altitudes.
PMID- 28418074
TI - The effects of genome duplications in a community context.
AB - Contents 57 I. 57 II. 59 III. 59 IV. 63 V. 64 VI. 64 VII. 66 66 References 66
SUMMARY: Whole-genome duplication (WGD), or polyploidy, has important effects on
the genotype and phenotype of plants, potentially altering ecological
interactions with other organisms. Even though the connections between polyploidy
and species interactions have been recognized for some time, we are only just
beginning to test whether WGD affects community context. Here I review the sparse
information on polyploidy and community context and then present a set of
hypotheses for future work. Thus far, community-level studies of polyploids
suggest an array of outcomes, from no changes in community context to shifts in
the abundance and composition of interacting species. I propose a number of
mechanisms for how WGD could alter community context and how the emergence of
polyploids in populations could also alter the community context of parental
diploids and other plant species. Resolving how and when these changes are
expected to occur will require a deeper understanding of the connections among
WGD, phenotypic changes, and the direct and indirect effects of species
interactions.
PMID- 28418075
TI - Horizontal gene transfer is less frequent in eukaryotes than prokaryotes but can
be important (retrospective on DOI 10.1002/bies.201300095).
PMID- 28418076
TI - Ultrasonic modulation of tissue optical properties in ex vivo porcine skin to
improve transmitted transdermal laser intensity.
AB - BACKGROUND AND OBJECTIVE: Applications of light-based energy devices involving
optical targets within the dermis frequently experience negative side-effects
resultant from surface scattering and excess optical absorption by epidermal
melanin. As a broadband optical absorber, melanin decreases the efficacy of light
based treatments throughout the ultraviolet, visible, and near-infrared spectra
while also generating additional heat within the surface tissue that can lead to
inflammation or tissue damage. Consequently, procedures may be performed using
greater energy densities to ensure that the target receives a clinically relevant
dose of light; however, such practices are limited, as doing so tends to
exacerbate the detrimental complications resulting from melanin absorption of
treatment light. The technique presented herein represents an alternative method
of operation aimed at increasing epidermal energy fluence while mitigating excess
absorption by unintended chromophores. The approach involves the application of
continuously pulsed ultrasound to modulate the tissue's optical properties and
thereby improve light transmission through the epidermis. MATERIALS AND METHODS:
To demonstrate the change in optical properties, pulsed light at a wavelength of
532 nm from a Q-switched Nd:YAG laser was transmitted into 4 mm thick samples of
porcine skin, comprised of both epidermal and dermal tissue. The light was
transmitted using an optical waveguide, which allowed for an ultrasonic
transducer to be incorporated for simultaneous paraxial pulsation in parallel
with laser operation. Light transmitted through the tissue was measured by a
photodiode attached to an integrating sphere. RESULTS: Increasing the driving
voltage of ultrasonic pulsation resulted in an increase in mean transmitted
optical power of up to a factor of 1.742 +/- 0.0526 times the control, wherein no
ultrasound was applied, after which the optical power increase plateaued to an
average amplification factor of 1.733 +/- 0.549 times the control. CONCLUSIONS:
The increase implies a reduction in light either back-scattered or absorbed
within the tissue, which would allow for a greater proportion of incident energy
to be delivered to the clinical target, thereby improving procedural efficacy and
potentially reducing the severity of detrimental side-effects. Apparatus Lasers
Surg. Med. 49:666-674, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28418077
TI - Therapeutic protein deimmunization by T-cell epitope removal: antigen-specific
immune responses in vitro and in vivo.
AB - Hirudin III is an effective anti-coagulant; however, in 40% of treated patients,
a high-titer of anti-Hirudin III IgG antibodies is observed. Development of
antibody responses requires the activation of helper T lymphocyte (HTL), which is
dependent on peptide epitopes binding to HLA class II molecules. Based on
computational prediction softwares, four new mutants of Hirudin III, T4K, S9G,
V21G, and V21K, had been designed with the aim of reducing the binding affinity
of these HTL epitopes. The constructed mutants have been purified and assayed for
bioactivity. Finally in vitro and in vivo cell-mediated responses were assessed
and humoral immune assays were performed. All modified forms of Hirudin III were
active, and showed significantly reduced human T-cell responses. All mutants
indicated lower human IFN-gamma level compared to native Hirudin, and V21K
indicated lowest IFN-gamma level. Mice immunized with T4K and V21K showed a
significant reduction in total antibody responses and mouse IFN-gamma levels.
Mice immunized with V21K after 3rd immunization had lower T-cell proliferation
compared to native Hirudin and other mutants. Based on these results, V21K is
proposed as the best alternate Hirudin III candidate with lowest antigenicity.
These findings validate our rational design strategy aimed at providing new
active analogs of therapeutic proteins with reduced immunogenicity.
PMID- 28418078
TI - Induction of mitochondrial apoptotic pathway in triple negative breast carcinoma
cells by methylglyoxal via generation of reactive oxygen species.
AB - Triple negative breast cancer (TNBC) tends to form aggressive tumors associated
with high mortality and morbidity which urge the need for development of new
therapeutic strategies. Recently, the normal metabolite Methylglyoxal (MG) has
been documented for its anti-proliferative activity against human breast cancer.
However, the mode of action of MG against TNBC remains open to question. In our
study, we investigated the anticancer activity of MG in MDA MB 231 and 4T1 TNBC
cell lines and elucidated the underlying mechanisms. MG dose-dependently caused
cell death, induced apoptosis, and generated ROS in both the TNBC cell lines.
Furthermore, such effects were attenuated in presence of ROS scavenger N-Acetyl
cysteine. MG triggered mitochondrial cytochrome c release in the cytosol and up
regulated Bax while down-regulated anti-apoptotic protein Bcl-2. Additionally, MG
treatment down-regulated phospho-akt and inhibited the nuclear translocation of
the p65 subunit of NF-kappaB. MG exhibited a tumor suppressive effect in BALB/c
mouse 4T1 breast tumor model as well. The cytotoxic effect was studied using MTT
assay. Apoptosis, ROS generation, and mitochondrial dysfunction was evaluated by
flow cytometry as well as fluorescence microscopy. Western blot assay was
performed to analyze proteins responsible for apoptosis. This study demonstrated
MG as a potent anticancer agent against TNBC both in vitro and in vivo. The
findings will furnish fresh insights into the treatment of this subgroup of
breast cancer.
PMID- 28418079
TI - Loneliness and cardiovascular disease and the role of late-life depression.
AB - OBJECTIVE: Loneliness and depression have a strong reciprocal influence, and both
predict adverse health outcomes at old age. Therefore, this study examines
whether loneliness is associated with the presence of cardiovascular diseases
taking into account the role of late-life depression. METHODS: Cross-sectional
data of 477 older adults in the Netherlands Study of Depressed Older Persons were
used. Logistic regression analysis was performed to examine the relation between
loneliness and cardiovascular disease. Depression was added to the regression
model to examine whether depression is an explanatory factor in the association
between loneliness and cardiovascular disease. Interaction terms between
loneliness and depression and between loneliness and sex were introduced in the
regression model to investigate whether depressed and non-depressed participants,
and men and women differed in their association between loneliness and
cardiovascular disease. RESULTS: Of the overall group, 61% were lonely, 28% had a
history of cardiovascular disease and 74% were depressed. Loneliness and
cardiovascular disease were not associated in the overall group after adjustment
for confounders (continuous: odds ratio [OR] = 1.04, 95% confidence interval [CI]
= 0.98-1.10), p = 0.25; dichotomous: OR = 1.27, 95% CI = 0.80-2.03, p = 0.32).
For women, there was an association between loneliness and cardiovascular
diseases (continuous: OR = 1.13, 95% CI = 1.06-1.21, p < 0.001; dichotomous: OR =
2.64, 95% CI = 1.50-4.65, p = 0.001), but this association was not present in men
(OR = 0.96, 95% CI = 0.88-1.05, p = 0.38). This association remained significant
after adjustment for confounders, but it lost significance after adding
depression to the model. CONCLUSION: For women only, there was an association
between loneliness and cardiovascular disease. However, this association was
explained by depression, indicating that loneliness in its own right seems not
related with cardiovascular disease. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28418080
TI - Phototoxic potential of undispersed and dispersed fresh and weathered Macondo
crude oils to Gulf of Mexico Marine Organisms.
AB - Crude oils contain a mixture of hydrocarbons, including phototoxic polycyclic
aromatic hydrocarbons (PAHs) that have the ability to absorb ultraviolet (UV)
light. Absorption of UV light by PAHs can substantially increase their toxicity
to marine organisms. The objective of the present study was to examine the
potential for phototoxicity of fresh and naturally weathered Macondo crude oils
alone and in combination with the dispersant Corexit 9500 to mysid shrimp
(Americamysis bahia), inland silverside (Menidia beryllina), sheepshead minnow
(Cyprinodon variegatus), and Gulf killifish (Fundulus grandis). Acute toxicity
tests were conducted using combinations of natural or artificial sunlight and low
energy water-accommodated fractions (WAFs) of fresh and weathered Macondo crude
oils collected from the Gulf of Mexico. Studies were also conducted to compare
the phototoxicity resulting from natural and artificial sunlight. Fresh Macondo
crude oil was more phototoxic than weathered crude oils, both in the presence and
in the absence of UV light. Differences in toxicity between fresh and weathered
crude oils were likely attributed to lighter-ringed PAHs in fresh crude oils.
Phototoxic PAHs were relatively resistant to weathering compared with lighter
ringed PAHs. The addition of Corexit 9500 to crude oil increased toxicity
compared with tests with crude oil alone, by increasing phototoxic PAH
concentrations in WAFs. Macondo crude oils had the potential to be phototoxic to
Gulf of Mexico marine organisms if specific light conditions and PAH
concentrations were present during the Deepwater Horizon oil spill. Environ
Toxicol Chem 2017;36:2640-2650. (c) 2017 SETAC.
PMID- 28418081
TI - Assessment of biofilm removal capacity of a broad host range bacteriophage JHP
against Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa is an efficient biofilm-dwelling microbial pathogen,
associated with nosocomial infections. These biofilm-associated infections are
resistant to antibiotics and immune defenses, therefore pose major problem
against their treatment. This scenario demands alternative therapeutic regimens,
and bacteriophage therapy is one among potential strategies for clinical
management of multiple drug resistance. In this investigation, the efficacy of a
bacteriophage, JHP, is evaluated to eradicate P. aeruginosa biofilms. Growth
kinetics of P. aeruginosa biofilm revealed that the highest cell density biofilm
(1.5 * 1016 CFU/mL) was established within the polystyrene microtiter plate at 72
h post inoculation. Pseudomonas aeruginosa biofilms of different ages, treated
with JHP (0.6 MOI) for different post-infection durations, reduced biomass from 2
to 4.5 logs (60-90%). JHP treatment before biofilm development reduced the
bacterial load up to 9 logs (>95% bacterial load reduction) as compared with
untreated control, which highlights its potential to prevent biofilm formation in
indwelling medical devices. Combinations of JHP with other phages or antibiotics
could be an efficient alternative for P. aeruginosa biofilm removal in clinical
and industrial settings.
PMID- 28418082
TI - Non-digestible carbohydrates supplementation increases miR-32 expression in the
healthy human colorectal epithelium: A randomized controlled trial.
AB - Colorectal cancer (CRC) risk is modulated by diet and there is convincing
evidence of reduced risk with higher non-digestible carbohydrates (NDCs)
consumption. Resistant starch (RS), a NDC, positively modulates the expression of
oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs
protect against CRC. The present study aimed to investigate the effects of
supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression
in the macroscopically-normal human rectal epithelium using samples from the DISC
Study, a randomized, double-blind, placebo-controlled dietary intervention. We
screened 1008 miRNAs in pooled post-intervention rectal mucosal samples from
participants allocated to the double placebo group and those supplemented with
both RS and PD. A total of 111 miRNAs were up- or down-regulated by at least
twofold in the RS + PD group compared with the control group. From these, eight
were selected for quantification in individual participant samples by qPCR, and
fold-change direction was consistent with the array for seven miRNAs. The
inconsistency for miR-133b and the lower fold-change values observed for the
seven miRNAs is probably because qPCR of individual participant samples is a more
robust and sensitive method of quantification than the array. miR-32 expression
was increased by approximately threefold (P = 0.033) in the rectal mucosa of
participants supplemented with RS + PD compared with placebo. miR-32 is involved
in the regulation of processes such as cell proliferation that are dysregulated
in CRC. Furthermore, miR-32 may affect non-canonical NF-kappaB signaling via
regulation of TRAF3 expression and consequently NIK stabilization.
PMID- 28418083
TI - Interannual variation in methane emissions from tropical wetlands triggered by
repeated El Nino Southern Oscillation.
AB - Methane (CH4 ) emissions from tropical wetlands contribute 60%-80% of global
natural wetland CH4 emissions. Decreased wetland CH4 emissions can act as a
negative feedback mechanism for future climate warming and vice versa. The impact
of the El Nino-Southern Oscillation (ENSO) on CH4 emissions from wetlands remains
poorly quantified at both regional and global scales, and El Nino events are
expected to become more severe based on climate models' projections. We use a
process-based model of global wetland CH4 emissions to investigate the impacts of
the ENSO on CH4 emissions in tropical wetlands for the period from 1950 to 2012.
The results show that CH4 emissions from tropical wetlands respond strongly to
repeated ENSO events, with negative anomalies occurring during El Nino periods
and with positive anomalies occurring during La Nina periods. An approximately 8
month time lag was detected between tropical wetland CH4 emissions and ENSO
events, which was caused by the combined time lag effects of ENSO events on
precipitation and temperature over tropical wetlands. The ENSO can explain 49% of
interannual variations for tropical wetland CH4 emissions. Furthermore, relative
to neutral years, changes in temperature have much stronger effects on tropical
wetland CH4 emissions than the changes in precipitation during ENSO periods. The
occurrence of several El Nino events contributed to a lower decadal mean growth
rate in atmospheric CH4 concentrations throughout the 1980s and 1990s and to
stable atmospheric CH4 concentrations from 1999 to 2006, resulting in negative
feedback to global warming.
PMID- 28418084
TI - Epstein-Barr virus infection induces genome-wide de novo DNA methylation in non
neoplastic gastric epithelial cells.
AB - Epstein-Barr virus (EBV)-positive gastric cancer (GC) shows a higher DNA
methylation epigenotype. EBV infection can causally induce genome-wide aberrant
DNA methylation, as previously demonstrated by in vitro infection experiments in
the low-methylation GC cell line MKN7. However, whether EBV exerts DNA
methylation remodelling properties in non-neoplastic epithelial cells remains
unclear. Here we performed post-infection time-series DNA methylation analyses
using the immortalized normal gastric epithelial cell line GES1. Genome-wide
analysis using Illumina's Infinium 450 k BeadArray demonstrated global de novo
DNA methylation from post-infection day 17, which was completed by 28 days in a
manner similar to that observed in MKN7 cells. De novo methylation of all types
of GC-specific methylation marker genes was observed, indicating that EBV
infection is sufficient for gastric epithelial cells to acquire an EBV-positive
GC epigenotype. Pyrosequencing demonstrated that methylation of the viral genome
preceded that of the host cellular genome, suggesting the existence of well
ordered mechanisms that induce methylation. Spatiotemporal representation with
differential models revealed dynamic alterations of DNA methylation in promoter
regions, occurring from lower-CpG peripheral regions and extending to higher-CpG
core regions. In summary, EBV infection exerted powerful pressure to induce
global de novo DNA methylation in non-neoplastic cells within a month in a
spatiotemporally well-ordered manner. Copyright (c) 2017 Pathological Society of
Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID- 28418086
TI - General dentists' use of diagnostic equipment and methods.
AB - An accurate diagnosis is essential for making treatment decisions in dentistry.
However, little research is available as to which tests are done routinely and
how commonly they are performed. The purpose of this study was to investigate
diagnostic methods and equipment used by general dentists in private practice in
Perth. The study involved a retrospective audit of 30 patient records from seven
individual general dentists working in private practices in the Perth
Metropolitan area. De-identification of patient records was done prior to the
researchers' visit. Radiographs were the most commonly used diagnostic tool.
Percussion was also commonly employed, followed by cold pulp testing and
mobility. The most commonly used tests were radiographs, percussion, periodontal
probing and visual examination. The frequency of these tests differed depending
on whether the patient presented with or without pain, with percussion and cold
tests used more frequently when the patient presented with pain.
PMID- 28418085
TI - Puquitinib, a novel orally available PI3Kdelta inhibitor, exhibits potent
antitumor efficacy against acute myeloid leukemia.
AB - The PI3Kdelta isoform (PIK3CD), also known as P110delta, is predominately
expressed in leukocytes and has been implicated as a potential target in the
treatment of hematological malignancies. In this report, we detailed the
pharmacologic properties of puquitinib, a novel, orally available PI3Kdelta
inhibitor. Puquitinib, which binds to the ATP-binding pocket of PI3Kdelta, was
highly selective and potent for PI3Kdelta relative to other PI3K isoforms and a
panel of protein kinases, exhibiting low-nanomolar biochemical and cellular
inhibitory potencies. Additional cellular profiling demonstrated that puquitinib
inhibited proliferation, induced G1 -phase cell-cycle arrest and apoptosis in
acute myeloid leukemia (AML) cell lines, through downregulation of PI3K
signaling. In in vivo AML xenografts, puquitinib alone showed stronger efficacy
than the well-known p110delta inhibitor, CAL-101, in association with a reduction
in AKT and ERK phosphorylation in tumor tissues, without causing noticeable
toxicity. Furthermore, the combination of puquitinib with cytotoxic drugs,
especially daunorubicin, yielded significantly stronger antitumor efficacy
compared with each agent alone. Thus, puquitinib is a promising agent with
pharmacologic properties that are favorable for the treatment of AML.
PMID- 28418087
TI - Traumatic stress-induced persistent changes in DNA methylation regulate
neuropeptide Y expression in rat jejunum.
AB - BACKGROUND: Stress-induced chronic neuropsychiatric conditions such as anxiety
are often co-morbid with gastrointestinal malfunctions. While we find enduring
anxiety-like symptoms following minimal traumatic brain injury (MTBI) in rats,
gastrointestinal consequences of MTBI remain elusive. METHODS: In this study, we
examined the effects of MTBI on a major gut peptide, neuropeptide Y (NPY) and gut
motility. DNA methylation was studied as a possible epigenetic mechanism
operative in the regulation of NPY expression in the gut. KEY RESULTS: Minimal
traumatic brain injury reduced the gut motility 48 hours and 30 days after
trauma. The expression of DNA methyltransferase isoforms (DNMT1, DNMT3a, and
DNMT3b) was altered in the jejunum 48 hours and 30 days after MTBI. However, the
mRNA levels of growth arrest and DNA damage 45 (GADD45) isoforms, GADD45a, and
GADD45b, which are believed to be involved in active DNA demethylation, initially
decreased at 48 hours but subsequently increased after 30 days of trauma.
Similarly, DNA hypomethylation at the NPY promoter region in the jejunum was
correlated with the increase in NPY mRNA and protein levels 30 days post-trauma.
On the other hand, DNA hypomethylation at 48 hours was associated with a decline
in NPY expression. Treatment with 5-azacytidine (5-AzaC), a DNMT inhibitor,
retarded DNA methylation and restored the NPY mRNA levels in the jejunum of MTBI
induced rats. CONCLUSIONS & INFERENCES: These results suggest that DNA
demethylation could be operative as an epigenetic mechanism in the long-term
regulation of NPY gene expression to alter the gut motility during traumatic
stress.
PMID- 28418088
TI - RACK1 forms a complex with FGFR1 and PKM2, and stimulates the growth and
migration of squamous lung cancer cells.
AB - Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth
factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as
well as cell growth in lung cancer. Better understanding the regulation of this
process would benefit the clinical treatment for lung cancer. Here, it has been
found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a
complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking
down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and
inhibited the growth and migration of lung cancer cells, while over-expression of
RACK1 in lung cancer cells led to the resistance to Erdafitinib. Moreover,
knocking down the expression of RACK1 impaired the tumorigenesis of lung cancer
driven by LKB loss and mutated Ras (KrasG12D). Taken together, our study
demonstrated the pivotal roles of RACK1 in FGFR1/PKM2 signaling, suggesting
FGFR1/RACK1/PKM2 might be a therapeutic target for lung cancer treatment.
PMID- 28418089
TI - Facts and values in psychotherapy-A critique of the empirical reduction of
psychotherapy within evidence-based practice.
AB - This paper addresses an implicit presupposition in research-supported
psychological treatments and evidence-based practice in psychology. It argues
that the notion of research-supported psychological treatments is based on a
reductive conceptualisation of psychotherapy. Research-supported psychological
treatments hinge upon an empirical reduction where psychotherapy schools become
conceptualized as mere collections of empirical propositions. However, this paper
argues that the different psychotherapy schools have distinct ethoses that are
constituted by normative claims. Consequently, the evaluation of the different
psychotherapy schools and the practice of psychotherapy should include the
underlying normative claims of these ethoses.
PMID- 28418091
TI - Newsworthiness vs scientific impact: are the most highly cited urology papers the
most widely disseminated in the media?
AB - OBJECTIVE: To assess whether a correlation exists between newsworthiness
(Altmetric score) and scientific impact markers, such as citation analysis,
impact factors, and levels of evidence. METHODS: The top five most cited articles
for the year 2014 and 2015 from the top 10 ranking urology journals (Scientific
Impact Group) were identified. The top 50 articles each in 2014 and 2015 were
identified from Altmetric support based on media activity (Media Impact Group).
We determined the number of citations that these articles received in the
scientific literature, and calculated correlations between citations with
Altmetric scores. RESULTS: In the Scientific Impact Group, the mean number of
citations per article was 37.6, and the most highly cited articles were oncology
guidelines. The mean Altmetric score in these articles was 14.8. There was a weak
positive correlation between citations and Altmetric score (rs = 0.35, 95%
confidence interval 0.16-0.52, P < 0.001). In the Media Impact Group, the mean
Altmetric score was 121.1 and most widely shared articles all related to sexual
medicine. In this group, the mean number of citations was 9.7 and there was a
weak negative correlation between Altmetric score and citations (rs = -0.20, P =
0.046). CONCLUSION: The top articles based on Altmetric scores were not highly
cited, suggesting that publications receiving the most media attention may not be
the most scientifically rigorous, or that this audience places greater value on
different subjects than the scientific community.
PMID- 28418090
TI - Natural mortality and cause of death analysis of the captive chimpanzee (Pan
troglodytes): A 35-year review.
AB - We present the spontaneous causes of mortality for 137 chimpanzees (Pan
troglodytes) over a 35-year period. A record review of the pathology database was
performed and a primary cause of mortality was determined for each chimpanzee.
The most common causes of mortality were as follows: cardiomyopathy (40% of all
mortalities), stillbirth/abortion, acute myocardial necrosis, chimpanzee-induced
trauma, amyloidosis, and pneumonia. Five morphologic diagnoses accounted for 61%
of mortalities: cardiomyopathy, hemorrhage, acute myocardial necrosis,
amyloidosis, and pneumonia. The most common etiologies were degenerative,
undetermined, bacterial, traumatic, and neoplastic. The cardiovascular system was
most frequently involved, followed by the gastrointestinal, respiratory, and
multisystemic diseases. Degenerative diseases were the primary etiological cause
of mortality of the adult captive chimpanzee population. Chimpanzee-induced
trauma was the major etiological cause of mortality among the perinatal and
infant population. This information should be a useful resource for veterinarians
and researchers working with chimpanzees.
PMID- 28418092
TI - Atmospheric chlorinated polyfluorinated ether sulfonate and ionic perfluoroalkyl
acids in 2006 to 2014 in Dalian, China.
AB - Chlorinated polyfluorinated ether sulfonate (Cl-PFESA; trade name F-53B) is an
alternative product for perfluorooctane sulfonate (PFOS) used in metal plating;
little is known about its levels in the environment and its risks. To our
knowledge, the present study constitutes the first report of Cl-PFESA in the
atmosphere. In 2006 to 2014, C8 Cl-PFESA, along with ionic perfluoroalkyl acids
(PFAAs), was detected in atmospheric particulate matter in Dalian, China.
Concentrations of C8 Cl-PFESA increased from 140 pg/m3 in 2007 to 722 pg/m3 in
2014. Levels of 11 (total) ionic PFAAs increased in 2006 to 2008 and decreased
afterward, with a range of 35.7 to 860 pg/m3 . The PFAAs in the particulate
matter were dominated by perfluorocarboxylates, with perfluorooctanoate detected
at the highest concentration at a mean level of 71.7 pg/m3 , followed by
perfluoroheptanoate and perfluorohexanoate. Perfluorosulfonates were detected at
lower levels, with mean concentrations of PFOS, perfluorobutanesulfonate, and
perfluorohexane sulfonate of 5.73, 1.64, and 1.24 pg/m3 , respectively. Back
trajectory analysis suggested that the air mass approaching Dalian during the
sampling originated from the northwest, where fluorochemical industry parks and
metal plating industries are densely located. No significant correlation was
observed between Cl-PFESA and the ionic PFAAs. The relatively high Cl-PFESA
concentrations suggested that it possibly contributed largely to the previously
reported exposure to undefined organic fluorine compounds, for which further
research on emission and environmental risks is needed. Environ Toxicol Chem
2017;36:2581-2586. (c) 2017 SETAC.
PMID- 28418094
TI - The skin microbiome of the common thresher shark (Alopias vulpinus) has low
taxonomic and gene function beta-diversity.
AB - The health of sharks, like all organisms, is linked to their microbiome. At the
skin interface, sharks have dermal denticles that protrude above the mucus, which
may affect the types of microbes that occur here. We characterized the microbiome
from the skin of the common thresher shark (Alopias vulpinus) to investigate the
structure and composition of the skin microbiome. On average 618 812 (80.9% +/-
S.D. 0.44%) reads per metagenomic library contained open reading frames; of
those, between 7.6% and 12.8% matched known protein sequences. Genera
distinguishing the A. vulpinus microbiome from the water column included,
Pseudoalteromonas (12.8% +/- 4.7 of sequences), Erythrobacter (5. 3% +/- 0.5) and
Idiomarina (4.2% +/- 1.2) and distinguishing gene pathways included, cobalt, zinc
and cadmium resistance (2.2% +/- 0.1); iron acquisition (1.2% +/- 0.1) and
ton/tol transport (1.3% +/- 0.08). Taxonomic community overlap (100 -
dissimilarity index) was greater in the skin microbiome (77.6), relative to the
water column microbiome (70.6) and a reference host-associated microbiome (algae:
71.5). We conclude the A. vulpinus skin microbiome is influenced by filtering
processes, including biochemical and biophysical components of the shark skin and
result in a structured microbiome.
PMID- 28418093
TI - Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but
enhances bone resorption activity via prolyl-4-hydroxylase 2.
AB - Osteogenic-angiogenic coupling is promoted by the hypoxia-inducible factor 1
alpha (HIF-1alpha) transcription factor, provoking interest in HIF activation as
a therapeutic strategy to improve osteoblast mineralization and treat
pathological osteolysis. However, HIF also enhances the bone-resorbing activity
of mature osteoclasts. It is therefore essential to determine the full effect(s)
of HIF on both the formation and the bone-resorbing function of osteoclasts in
order to understand how they might respond to such a strategy. Expression of HIF
1alpha mRNA and protein increased during osteoclast differentiation from CD14+
monocytic precursors, additionally inducing expression of the HIF-regulated
glycolytic enzymes. However, HIF-1alpha siRNA only moderately affected osteoclast
differentiation, accelerating fusion of precursor cells. HIF induction by
inhibition of the regulatory prolyl-4-hydroxylase (PHD) enzymes reduced
osteoclastogenesis, but was confirmed to enhance bone resorption by mature
osteoclasts. Phd2+/- murine osteoclasts also exhibited enhanced bone resorption,
associated with increased expression of resorption-associated Acp5, in comparison
with wild-type cells from littermate controls. Phd3-/- bone marrow precursors
displayed accelerated early fusion, mirroring results with HIF-1alpha siRNA. In
vivo, Phd2+/- and Phd3-/- mice exhibited reduced trabecular bone mass, associated
with reduced mineralization by Phd2+/- osteoblasts. These data indicate that HIF
predominantly functions as a regulator of osteoclast-mediated bone resorption,
with little effect on osteoclast differentiation. Inhibition of HIF might
therefore represent an alternative strategy to treat diseases characterized by
pathological levels of osteolysis. (c) 2017 The Authors. The Journal of Pathology
published by John Wiley & Sons Ltd on behalf of Pathological Society of Great
Britain and Ireland.
PMID- 28418096
TI - Expression of toll-like receptors in T lymphocytes stimulated with N-(3
oxododecanoyl)-L-homoserine lactone from Pseudomonas aeruginosa.
AB - The establishment of chronic Pseudomonas aeruginosa infections is correlated with
the disturbance of the host immune system. The P. aeruginosa quorum-sensing
molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL) has the potential
to modulate the host immune system. The immune system recognizes pathogens via
toll-like receptors (TLRs). We found that 3-O-C12-HSL induced TLR changes in
monocytes. However, the role of T cells in P. aeruginosa infection has not been
delineated. In order to understand this activity, we examined whether 3-O-C12-HSL
has an effect on the immune function and the expression of TLRs in T lymphocytes.
Human peripheral blood mononuclear cells (PBMCs) cells were cultured with 0, 1,
10, 50, or 100 MUM 3-O-C12-HSL for 12 h. TLR2/TLR4 expression and T-lymphocyte
proliferation were increased in a dose-dependent manner, and 100 MUM 3-O-C12-HSL
significantly increased TLR2 expression. Moreover, tumor necrosis factor-alpha
production of these PBMCs was inhibited. To conclude, 3-O-C12-HSL can induce
lymphocyte cell proliferation. These findings provide a new perspective on our
understanding of the persistence of the chronic inflammation that accompanies P.
aeruginosa infection.
PMID- 28418095
TI - The nuclear orphan receptor NR4A1 regulates beta1-integrin expression in
pancreatic and colon cancer cells and can be targeted by NR4A1 antagonists.
AB - beta1-Integrin is highly expressed and is a negative prognostic factor for colon
and pancreatic cancer patients and the gene plays a functional role in cell
migration and invasion. In this study, we demonstrate that beta1-integrin
expression is regulated in pancreatic and colon cancer cells by the pro-oncogenic
orphan nuclear receptor 4A1 (NR4A1, Nur77, TR3) and knockdown of this receptor by
RNA interference decreases beta1-integrin protein and mRNA expression, alpha5
integrin, and also expression of beta1-integrin-dependent phosphorylation of FAK
(pFak). Knockdown of NR4A1 also decreased migration and fibronectin-induced
adhesion in pancreatic (Panc1, L3.6 pL, and MiaPaCa2) and colon (RKO and SW480)
cancer cells. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methane (C-DIM)
compounds containing p-hydroxy (DIM-C-pPhOH) and p-carbomethoxy (DIM-C-pPhCO2 Me)
groups are NR4A1 ligands that act as antagonists for this receptor. Treatment of
pancreatic and colon cancer cells with DIM-C-pPhOH or DIM-C-pPhCO2 Me mimics the
effects of NR4A1 knockdown and decreases beta1-integrin expression, beta1
integrin regulated genes and responses including migration and adhesion. The
results demonstrate a novel method for targeting beta1-integrin in colon and
pancreatic cancer cells and indicate possible clinical applications for C
DIM/NR4A1 antagonists for pancreatic and colon cancer therapy.
PMID- 28418097
TI - Genome and epigenome of a novel marine Thaumarchaeota strain suggest viral
infection, phosphorothioation DNA modification and multiple restriction systems.
AB - Marine Thaumarchaeota are abundant ammonia-oxidizers but have few representative
laboratory-cultured strains. We report the cultivation of Candidatus
Nitrosomarinus catalina SPOT01, a novel strain that is less warm-temperature
tolerant than other cultivated Thaumarchaeota. Using metagenomic recruitment,
strain SPOT01 comprises a major portion of Thaumarchaeota (4-54%) in temperate
Pacific waters. Its complete 1.36 Mbp genome possesses several distinguishing
features: putative phosphorothioation (PT) DNA modification genes; a region
containing probable viral genes; and putative urea utilization genes. The PT
modification genes and an adjacent putative restriction enzyme (RE) operon likely
form a restriction modification (RM) system for defence from foreign DNA. PacBio
sequencing showed >98% methylation at two motifs, and inferred PT guanine
modification of 19% of possible TGCA sites. Metagenomic recruitment also reveals
the putative virus region and PT modification and RE genes are present in 18-26%,
9-14% and <1.5% of natural populations at 150 m with >=85% identity to strain
SPOT01. The presence of multiple probable RM systems in a highly streamlined
genome suggests a surprising importance for defence from foreign DNA for dilute
populations that infrequently encounter viruses or other cells. This new strain
provides new insights into the ecology, including viral interactions, of this
important group of marine microbes.
PMID- 28418098
TI - Stress and subsidy effects of seagrass wrack duration, frequency, and magnitude
on salt marsh community structure.
AB - Environmental perturbations can strongly affect community processes and ecosystem
functions by acting primarily as a subsidy that increases productivity, a stress
that decreases productivity, or both, with the predominant effect potentially
shifting from subsidy to stress as the overall intensity of the perturbation
increases. While perturbations are often considered along a single axis of
intensity, they consist of multiple components (e.g., magnitude, frequency, and
duration) that may not have equivalent stress and/or subsidy effects. Thus,
different combinations of perturbation components may elicit community and
ecosystem responses that differ in strength and/or direction (i.e., stress or
subsidy) even if they reflect a similar overall perturbation intensity. To assess
the independent and interactive effects of perturbation components, we
experimentally manipulated the magnitude, frequency, and duration of wrack
deposition, a common stress-subsidy in a variety of coastal systems. The effects
of wrack perturbation on salt marsh community and ecosystem properties were
assessed both in the short-term (at the end of a 12-week experimental
manipulation) and long-term (6 months after the end of the experiment). In the
short-term, plants and associated benthic invertebrates exhibited primarily
stress-based responses to wrack perturbation. The extent of these stress effects
on density of the dominant plant Spartina alterniflora, total plant percent
cover, invertebrate abundance, and sediment oxygen availability were largely
determined by perturbation duration. Yet, higher nitrogen content of Spartina,
which indicates a subsidy effect of wrack, was influenced primarily by
perturbation magnitude in the short-term. In the longer term, perturbation
magnitude determined the extent of both stress and subsidy effects of wrack
perturbation, with lower subordinate plant percent cover and snail density, and
higher Spartina nitrogen content in high wrack biomass treatments. However,
stress effects on the marsh community were generally less pronounced 6 months
after the wrack perturbation, indicating capacity for recovery. Our results
demonstrate that individual perturbation components can determine the degree to
which its effects on the community elicit primarily stress- and/or subsidy-based
responses. Further, the nature and extent of stress-subsidy effects can change
over time, depending on species' relative ability to tolerate and/or recover from
perturbation.
PMID- 28418099
TI - Influence of Divalent Counterions on the Dynamics in DNA as Probed by Using a
Minor-Groove Binder.
AB - DNA dynamics, to which water, counterions, and DNA motions contribute, is a topic
of considerable interest because it is closely related to the efficiency of
biological functions performed by it. Simulation studies and experiments suggest
that the counterion dynamics in DNA probed by a minor-groove binder are similar
for various monovalent counterions. To date, the influence on DNA dynamics of
higher-valence counterions, which are also present around DNA and are known to
bind more strongly to it than monovalent ions, has not been studied. Herein we
investigated DNA dynamics in the presence of Mg2+ and Ca2+ , chosen for their
relative abundance in cells, by using minor-groove binder 4',6-diamidino-2
phenylindole (DAPI) as a fluorescence probe. The dynamics, as measured from the
time-resolved fluorescence Stokes shifts of DAPI bound to calf thymus DNA on a
subpicosecond-to-nanosecond timescale, were found to be very similar in the
presence of both the divalent ions and Na+ ions. The observation is explained by
considering the screening of the electric field of the divalent ion by its
hydration shell, preferential binding of the ions to the phosphate groups, and
displacement of ions from the minor groove by DAPI due to the stronger binding
interaction of the latter. Furthermore, the similarity of our results in the
presence of Na+ to those reported for smaller oligonucleotides suggests that the
chain length of DNA does not influence the DNA dynamics.
PMID- 28418100
TI - A surprisingly big role for big K+ channels in retinal horizontal cells.
PMID- 28418101
TI - Effect of an electronic medication administration record application on patient
safety.
AB - RATIONALE, AIMS, AND OBJECTIVES: To evaluate the effect of an electronic
medication administration record (eMAR) application on the rate of medication
errors in medication administration recording (ME-MAR). METHODS: A before-and
after, quasiexperimental study was conducted in a university hospital that
implemented the eMAR application in March 2014. Data collection was conducted in
April 2012 (pre-) and June 2014 (post-) by two pharmacists. The ME-MARs were
analysed by the staff involved to identify their cause. The two pharmacists
independently classified the ME-MARs. In the case of disagreement, a research
team examined the ME-MARs and categorized them by consensus. Three
classifications were used: A classic medication error taxonomy and 2 technology
induced error taxonomies. RESULTS: The pharmacists analysed 2835 (pre-) and 2621
(post-) medication administration records (MAR), respectively. Overall, the ME
MAR rate decreased from 48.0% (pre-) to 36.9% (post-) (P < .05). The same types
of ME-MAR were observed in both phases except for "MAR with incomplete
information," which was not observed in the postimplementation phase. In both
phases, the most frequent ME-MAR was "MAR at the wrong time" (MAR before or after
medication administration) (31.6% vs 30.2%). The main cause of ME-MARs in both
phases was the failure to follow work procedures. The potential future risk of ME
MARs significantly decreased after the eMAR implementation (P < .05). All ME-MARs
were "use errors" because of human factors. New ME-MARs (1.24%; n = 12) were
observed in the postimplementation phase. CONCLUSION: Use of the eMAR application
significantly reduces the rate of ME-MAR and their potential risk. The main cause
of ME-MAR was the failure to follow work procedures.
PMID- 28418102
TI - Efficacy and safety of combinations of mirabegron and solifenacin compared with
monotherapy and placebo in patients with overactive bladder (SYNERGY study).
AB - OBJECTIVE: To evaluate the potential of solifenacin 5 mg combined with mirabegron
25 or 50 mg to deliver superior efficacy compared with monotherapy, with
acceptable tolerability, in the general overactive bladder (OAB) population with
urinary incontinence (UI). PATIENTS AND METHODS: After a 4-week placebo run-in,
patients aged >=18 years with wet OAB (urgency, urinary frequency and UI) for >=3
months who recorded on average >=8 micturitions/24 h, >=1 urgency episode/24 h,
and >=3 UI episodes over the 7-day micturition diary, were eligible for
randomisation to double-blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg +
mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg
(combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg;
or placebo for 12 weeks], and 2-weeks' single-blind, placebo run-out. Co-primary
efficacy variables were change from baseline to end of treatment (EoT) in the
mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7-day
electronic micturition diary. Secondary efficacy variables included change from
baseline to EoT in the mean volume voided/micturition, change from baseline at
weeks 4, 8, 12 and EoT in mean number of UI episodes/24 h, micturitions/24 h,
urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h;
the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in
the last 7 days prior to each visit, micturition frequency normalisation (<8
episodes/24 h) at weeks 4, 8, 12 and EoT; and the number of UUI episodes and
nocturia episodes in the 7-day diary. Safety assessments included incidence and
frequency of treatment-emergent adverse events (TEAEs), post-void residual (PVR)
urine volume, and changes from baseline in laboratory parameters. RESULTS: Whilst
the combined S5 + M50 group was superior to solifenacin 5 mg for UI, with a mean
(standard error) adjusted difference of -0.20 (0.12) UI episodes/24 h (95%
confidence interval -0.44, 0.04, P = 0.033), there was no statistical superiority
vs mirabegron 50 mg [-0.23 (0.12) UI episodes/24 h; P = 0.052]. In secondary
analyses, all active treatment groups had greater improvements in UI episodes/24
h vs placebo, with effect sizes for the combined therapy groups (combined S5 +
M25 group: -0.70 episodes/24 h; combined S5 + M50 group: -0.65 episodes/24 h)
that were substantially higher than those obtained with monotherapy (range -0.37
episodes/24 h for mirabegron 25 mg to -0.45 episodes/24 h for solifenacin 5 mg).
For micturitions/24 h, adjusted change from baseline to EoT was greater in the
combined therapy groups vs monotherapies (combined S5 + M50 group, nominal P
values 0.006 and <0.001 vs solifenacin 5 mg and mirabegron 50 mg, respectively;
combined S5 + M25 group, nominal P values 0.040 and 0.001 vs solifenacin 5 mg and
mirabegron 25 mg, respectively). All active treatment groups had greater
improvements in the mean numbers of micturitions/24 h vs placebo, with effect
sizes for the combined therapy groups (combined S5 + M25 group: -0.85
micturitions/24 h; combined S5 + M50 group: -0.95 micturitions/24 h) higher than
with mirabegron monotherapy (25 mg: -0.36; 50 mg: -0.39 micturitions/24 h) and
solifenacin 5 mg (-0.56 micturitions/24 h). The combined S5 + M50 group was
statistically significantly superior to both monotherapies at EoT for UUI
episodes, urgency episodes and nocturia, with effect sizes that appeared to be
additive. The combined S5 + M25 group was statistically significantly superior to
mirabegron 25 mg for the same variables, except for nocturia. In responder
analyses at the EoT, odds ratios in favour of both combined therapies vs
monotherapies were shown for the proportion of patients with zero UI episodes and
those achieving micturition frequency normalisation. There was a slightly
increased frequency of TEAEs in the combined therapy groups vs monotherapies and
placebo. Most of the TEAEs were mild or moderate in severity. Events indicative
of urinary retention were reported slightly more frequently in the combined
therapy groups vs monotherapy and placebo. PVR volume was slightly increased in
the combined therapy groups vs solifenacin 5 mg, mirabegron monotherapy, and
placebo groups. There were slightly higher frequencies of dry mouth,
constipation, and dyspepsia in the combined therapy groups vs monotherapies.
There were no concerns regarding electrocardiograms and laboratory data.
CONCLUSION: In the largest OAB study to date, combined therapy with solifenacin 5
mg + mirabegron 25 mg and solifenacin 5 mg + mirabegron 50 mg provided consistent
improvements in efficacy compared with the respective monotherapies across most
of the outcome parameters, with effect sizes generally consistent with an
additive effect. Although the combined S5 + M50 group did not achieve a
statistically significant effect vs mirabegron 50 mg in the primary analysis of
one of the co-primary endpoints (change from baseline in mean number of UI
episodes/24 h), it approached statistical significance (P = 0.052), and the
nominal P values for the other co-primary endpoint (micturitions/24 h) were
<0.05. Most effects of combined therapy vs monotherapy were observable by week 4.
The clinical relevance of the improvements seen with combined therapy for several
objective OAB outcome measures was also supported by the improvements of combined
therapy vs monotherapy in the responder analyses.
PMID- 28418103
TI - Neurogenic and myogenic patterns of electrical activity in isolated intact mouse
colon.
AB - BACKGROUND: Relatively little is known about the electrical rhythmicity of the
whole colon, where long neural pathways are preserved. METHODS: Smooth muscle
electrical activity was recorded extracellularly from the serosa of isolated flat
sheet preparations consisting of the whole mouse colon (n=31). KEY RESULTS: Two
distinct electrical patterns were observed. The first, long intense spike bursts,
occurred every 349+/-256 seconds (0.2+/-0.2 cpm), firing action potentials for
31+/-11 seconds at 2.1+/-0.5 Hz. They were hexamethonium- and tetrodotoxin
sensitive, but persisted in nicardipine as 2 Hz electrical oscillations lacking
action potentials. This pattern is called here neurogenic spike bursts. The
second pattern, short spike bursts, occurred about every 30 seconds (2.0+/-0.6
cpm), with action potentials firing at about 1 Hz for 9 seconds (1.0+/-0.2 Hz,
9+/-4 seconds). Short spike bursts were hexamethonium- and tetrodotoxin-resistant
but nicardipine-sensitive and thus called here myogenic spike bursts. Neurogenic
spike bursts transiently delayed myogenic spike bursts, while blocking neurogenic
activity enhanced myogenic spike burst durations. External stimuli significantly
affected neurogenic but not myogenic spike bursts. Aboral electrical or
mechanical stimuli evoked premature neurogenic spike bursts. Circumferential
stretch significantly decreased intervals between neurogenic spike bursts.
Lesioning the colon down to 10 mm segments significantly increased intervals or
abolished neurogenic spike bursts, while myogenic spike bursts persisted.
CONCLUSIONS & INFERENCES: Distinct neurogenic and myogenic electrical patterns
were recorded from mouse colonic muscularis externa. Neurogenic spike bursts
likely correlate with neurogenic colonic migrating motor complexes (CMMC) and are
highly sensitive to mechanical stimuli. Myogenic spike bursts may correspond to
slow myogenic contractions, whose duration can be modulated by enteric neural
activity.
PMID- 28418104
TI - Is the nuclear refractive index lower than cytoplasm? Validation of phase
measurements and implications for light scattering technologies.
AB - The refractive index (RI) of biological materials is a fundamental parameter for
the optical characterization of living systems. Numerous light scattering
technologies are grounded in a quantitative knowledge of the refractive index at
cellular and subcellular scales. Recent work in quantitative phase microscopy
(QPM) has called into question the widely held assumption that the index of the
cell nucleus is greater than that of the cytoplasm, a result which disagrees with
much of the current literature. In this work, we critically examine the
measurement of the nuclear and whole-cell refractive index using QPM, validating
that nuclear refractive index is lower than that of cytoplasm in four diverse
cell lines and their corresponding isolated nuclei. We further examine Mie
scattering and phase-wrapping as potential sources of error in these
measurements, finding they have minimal impact. Finally, we use simulation to
examine the effects of incorrect RI assumptions on nuclear morphology
measurements using angle-resolved scattering information. Despite an erroneous
assumption of the nuclear refractive index, accurate measurement of nuclear
morphology was maintained, suggesting that light scattering modalities remain
effective.
PMID- 28418105
TI - Climate- and successional-related changes in functional composition of European
forests are strongly driven by tree mortality.
AB - Intense droughts combined with increased temperatures are one of the major
threats to forest persistence in the 21st century. Despite the direct impact of
climate change on forest growth and shifts in species abundance, the effect of
altered demography on changes in the composition of functional traits is not well
known. We sought to (1) quantify the recent changes in functional composition of
European forests; (2) identify the relative importance of climate change, mean
climate and forest development for changes in functional composition; and (3)
analyse the roles of tree mortality and growth underlying any functional changes
in different forest types. We quantified changes in functional composition from
the 1980s to the 2000s across Europe by two dimensions of functional trait
variation: the first dimension was mainly related to changes in leaf mass per
area and wood density (partially related to the trait differences between
angiosperms and gymnosperms), and the second dimension was related to changes in
maximum tree height. Our results indicate that climate change and mean climatic
effects strongly interacted with forest development and it was not possible to
completely disentangle their effects. Where recent climate change was not too
extreme, the patterns of functional change generally followed the expected
patterns under secondary succession (e.g. towards late-successional short
statured hardwoods in Mediterranean forests and taller gymnosperms in boreal
forests) and latitudinal gradients (e.g. larger proportion of gymnosperm-like
strategies at low water availability in forests formerly dominated by broad
leaved deciduous species). Recent climate change generally favoured the dominance
of angiosperm-like related traits under increased temperature and intense
droughts. Our results show functional composition changes over relatively short
time scales in European forests. These changes are largely determined by tree
mortality, which should be further investigated and modelled to adequately
predict the impacts of climate change on forest function.
PMID- 28418106
TI - Student-derived solutions to address barriers hindering reports of unprofessional
behaviour.
AB - BACKGROUND: Barriers hinder medical students from reporting breaches in
professional behaviour, which can adversely impact institutional culture. No
studies have reported student perspectives on how to address these barriers
successfully. Our study (i) evaluated the likelihood of reporting based on
violation severity, (ii) assessed barriers to reporting and (iii) elicited
students' proposed solutions. METHODS: Four medical students designed a cross
sectional study in 2015. In response to seven scenarios, students rated the
likelihood of reporting the violation, indicated perceived barriers and
identified solutions. Additional questions investigated the perceived importance
of professionalism, confidence in understanding professionalism and trust in
administrative protection from negative consequences. RESULTS: Two hundred and
seventy-two students in their clinical years (MS2-4) responded to the survey (RR
= 50%). Students were 70-90% likely to report major violations, but < 30% likely
to report minor or moderate violations. Barriers included concerns about an
uncomfortable relationship (41%), potential negative repercussions on grades or
opportunities (23%), and addressing by direct discussion rather than reporting
(23%). Solutions included simplified reporting, control over report release date,
improved feedback to reporters, training for real-time resolution of concerns and
a neutral resource to help students triage concerns. No differences existed
between classes regarding the importance or understanding of professionalism. In
linear regression, only importance of professionalism predicted likelihood of
reporting and this did not change with training. CONCLUSIONS: Hindered by common
barriers, students are unlikely to report a violation unless it is a serious
breach of professionalism. Student-derived solutions should be explored by
medical school administrators to encourage reporting of violation of
professionalism.
PMID- 28418107
TI - A new path in defining light parameters for hair growth: Discovery and modulation
of photoreceptors in human hair follicle.
AB - BACKGROUND AND OBJECTIVE: Though devices for hair growth based on low levels of
light have shown encouraging results, further improvements of their efficacy is
impeded by a lack of knowledge on the exact molecular targets that mediate
physiological response in skin and hair follicle. The aim of this study was to
investigate the expression of selected light-sensitive receptors in the human
hair follicle and to study the impact of UV-free blue light on hair growth ex
vivo. MATERIAL AND METHODS: The expression of Opsin receptors in human skin and
hair follicles has been characterized using RT-qPCR and immunofluorescence
approaches. The functional significance of Opsin 3 was assessed by silencing its
expression in the hair follicle cells followed by a transcriptomic profiling.
Proprietary LED-based devices emitting two discrete visible wavelengths were used
to access the effects of selected optical parameters on hair growth ex vivo and
outer root sheath cells in vitro. RESULTS: The expression of OPN2 (Rhodopsin) and
OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin
and anagen hair follicle. Treatment with 3.2 J/cm2 of blue light with 453 nm
central wavelength significantly prolonged anagen phase in hair follicles ex vivo
that was correlated with sustained proliferation in the light-treated samples. In
contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did
not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair
follicle outer root sheath cells resulted in the altered expression of genes
involved in the control of proliferation and apoptosis, and abrogated stimulatory
effects of blue light (3.2 J/cm2 ; 453 nm) on proliferation in the outer root
sheath cells. CONCLUSIONS: We provide the first evidence that (i) OPN2 and OPN3
are expressed in human hair follicle, and (ii) A 453 nm blue light at low radiant
exposure exerts a positive effect on hair growth ex vivo, potentially via
interaction with OPN3. Lasers Surg. Med. 49:705-718, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28418108
TI - Metabolic characterization and transformation of the non-dairy Lactococcus lactis
strain KF147, for production of ethanol from xylose.
AB - The non-dairy lactic acid bacterium Lactococcus lactis KF147 can utilize xylose
as the sole energy source. To assess whether KF147 could serve as a platform
organism for converting second generation sugars into useful chemicals, the
authors characterized growth and product formation for KF147 when grown on
xylose. In a defined medium KF147 was found to co-metabolize xylose and arginine,
resulting in bi-phasic growth. Especially at low xylose concentrations, arginine
significantly improved growth rate. To facilitate further studies of the xylose
metabolism, the authors eliminated arginine catabolism by deleting the arcA gene
encoding the arginine deiminase. The fermentation product profile suggested two
routes for xylose degradation, the phosphoketolase pathway and the pentose
phosphate pathway. Inactivation of the phosphoketolase pathway redirected the
entire flux through the pentose phosphate pathway whereas over-expression of
phosphoketolase increased the flux through the phosphoketolase pathway. In
general, significant amounts of the mixed-acid products, including lactate,
formate, acetate and ethanol, were formed irrespective of xylose concentrations.
To demonstrate the potential of KF147 for converting xylose into useful chemicals
the authors chose to redirect metabolism towards ethanol production. A synthetic
promoter library was used to drive the expression of codon-optimized versions of
the Zymomonas mobilis genes encoding pyruvate decarboxylase and alcohol
dehydrogenase, and the outcome was a strain producing ethanol as the sole
fermentation product with a high yield corresponding to 83% of the theoretical
maximum. The results clearly indicate the great potential of using the more
metabolically diverse non-dairy L. lactis strains for bio-production based on
xylose containing feedstocks.
PMID- 28418110
TI - Identification of circulating miRNA involved in meat yield of Korean cattle.
AB - Cattle plays an important role in providing essential nutrients through meat
production. Thus, we focused on epigenetic factors associated with meat yield. To
investigate circulating miRNAs that are involved with meat yield and connect
biofluids and longissimus dorsi (LD) muscle in Korean cattle, we performed
analyses of the carcass characteristics, miRNA array, qPCR, and bioinformatics.
Carcass characteristics relative to the yield grade (YG) showed that the yield
index and rib eye area were the highest, whereas the backfat thickness was the
lowest for YG A (equal to high YG) cattle among the three YGs. miRNA array sorted
the circulating miRNAs that connect biofluids and LD muscle. miRNA qPCR showed
that miR-15a (r = 0.84), miR-26b (r = 0.91), and miR-29c (r = 0.92) had positive
relationships with biofluids and LD muscle. In YG A cattle, miR-26b was
considered to be a circulating miRNA connecting biofluids and LD muscle because
the target genes of miR-26b were more involved with myogenesis. Then, miR-26b
targeted genes, DIAPH3 and YOD1, were downregulated in YG A cattle. Our results
suggest that miR-15a, miR-26b, and miR-29c are upregulated in biofluids and LD
muscle, whereas DIAPH3 and YOD1 are downregulated in the LD muscle of finishing
cattle steers.
PMID- 28418109
TI - Sagittal crest formation in great apes and gibbons.
AB - The frequency of sagittal crest expression and patterns of sagittal crest growth
and development have been documented in hominoids, including some extinct hominin
taxa, and the more frequent expression of the sagittal crest in males has been
traditionally linked with the need for larger-bodied individuals to have enough
attachment area for the temporalis muscle. In the present study, we investigate
sagittal cresting in a dentally mature sample of four hominoid taxa (Pan
troglodytes schweinfurthii, Gorilla gorilla gorilla, Pongo pygmaeus pygmaeus and
Hylobates lar). We investigate whether sagittal crest size increases with age
beyond dental maturity in males and females of G. g. gorilla and Po. pyg.
pygmaeus, and whether these taxa show sex differences in the timing of sagittal
crest development. We evaluate the hypothesis that the larger sagittal crest of
males may not be solely due to the requirement for a larger surface area than the
un-crested cranial vault can provide for the attachment of the temporalis muscle,
and present data on sex differences in temporalis muscle attachment area and
sagittal crest size relative to cranial size. Gorilla g. gorilla and Po. pyg.
pygmaeus males show significant relationships between tooth wear rank and
sagittal crest size, and they show sagittal crest size differences between age
groups that are not found in females. The sagittal crest emerges in early
adulthood in the majority of G. g. gorilla males, whereas the percentage of G. g.
gorilla females possessing a sagittal crest increases more gradually. Pongo pyg.
pygmaeus males experience a three-fold increase in the number of specimens
exhibiting a sagittal crest in mid-adulthood, consistent with a secondary growth
spurt. Gorilla g. gorilla and Po. pyg. pygmaeus show significant sex differences
in the size of the temporalis muscle attachment area, relative to cranial size,
with males of both taxa showing positive allometry not shown in females. Gorilla
g. gorilla males also show positive allometry for sagittal crest size relative to
cranial size. Our results suggest that although patterns of sagittal crest
expression have limited utility for taxonomy and phylogeny reconstruction, they
could be useful for reconstructing aspects of social behaviour in some extinct
hominin taxa. In particular, our results in G. g. gorilla and Po. pyg. pygmaeus,
which suggest that the size of sagittal crests in males cannot be solely
explained by the surface area required for attachment of the temporalis muscle,
offer partial support for the hypothesis that large sagittal crests form in
response to sexual selection and may play a role in social signalling.
PMID- 28418111
TI - Toward the Dark Matter of Natural Products.
AB - Considering the dynamic features of natural products, our access toward exploring
the entire diversity of natural products has been quite limited. It is
challenging to assess the diversity of natural products by using conventional
analytical methods, even with tandem chromatographic techniques, such as LC-MS
and GC-MS. This viewpoint is supported by the sequencing analyses of microbial
genomes, which have unveiled the potential of secondary metabolite production far
exceeding the number of isolated molecules. Recent advancements in metabolomics,
in concert with genomics analyses, have further extended the natural product
diversity, prompting growing awareness of the existence of reactive or short
lived natural molecules. This personal account introduces some examples of the
discoveries of hitherto elusive natural products, due to physico-chemical or
biological reasons, and highlights the significance of the dark matter of natural
products.
PMID- 28418112
TI - Photoresponsive Passive Micromixers Based on Spiropyran Size-Tunable Hydrogels.
AB - Microfluidic devices allow the manipulation of fluids down to the micrometer
scale and are receiving a lot of attention for applications where low volumes and
high throughputs are required. In these micro channels, laminar flow usually
dominates, which requires long residence times of the fluids, limiting the flow
speed and throughput. Here a switchable passive mixer has been developed to
control mixing and to easily clean microchannels. The mixer is based on a
photoresponsive spiropyran based hydrogel of which the dimensions can be tuned by
changing the intensity of the light. The size-tunable gels have been used to
fabricate a passive slanted groove mixer that can be switched off by light
allowing to change mixing of microfluidics to non-mixed flows. These findings
open new possibilities for multi-purpose microfluidic devices where mixers and
valves can be tuned by light.
PMID- 28418113
TI - Autochthonous Chagas disease in the southern United States: A case report of
suspected residential and military exposures.
AB - Chagas disease is a parasitic infection that can result in a progressive dilated
cardiomyopathy. Here, we present the epidemiologic details of a suspected locally
acquired transmission case originating from the southern United States. This is
the first published report of Chagas disease in a young, healthy United States
veteran with repeat triatomine exposures in Arizona. Military personnel and
Arizona residents should be aware of their Chagas disease transmission risks.
PMID- 28418114
TI - Hearing at speech frequencies is different from what we thought.
PMID- 28418116
TI - "What is the point of life?": An interpretative phenomenological analysis of
suicide in young menwith first-episode psychosis.
AB - BACKGROUND: Lifetime risk of suicide in first-episode psychosis far exceeds the
general population, with the risk of suicide persisting long after first
presentation. There is strong evidence to suggest that women more frequently
attempt suicide, while men are at a greater risk of completing suicide. First
hand experiential evidence is needed in order to better understand men's motives
for, and struggles with, suicidality in early psychosis. METHODS: Semi-structured
interviews were conducted with 7 participants. The interviews explored each
respondent's account of their suicide attempt within the broader context of their
life, in relation to their past, present and future. In line with the
exploratory, inductive nature of the study, an Interpretative Phenomenological
Analysis was used to explore the meaning of suicide attempts in these accounts.
RESULTS: Three super-ordinate themes emerged: Self-as-vulnerable (intra- and
inter-personal relationships), appraisal of cumulative life events as unbearable
and meaning of recovery marked by shared sense of hope and imagery for the
future. CONCLUSIONS: Young men in the early stages of their treatment are seeking
to find meaning for frightening, intrusive experiences with origins which often
precede psychosis. These experiences permeate personal identity, relationships
and recovery. Suicide was perceived as an escape from this conundrum, and was
pursued angrily and impulsively. By contrast, the attainment of hope was marked
by sharing one's burden and finding a sense of belonging. Specialized assertive
outreach programmes may be beneficial in improving the social inclusion of young
men who may be particularly marginalized.
PMID- 28418115
TI - Aggravation of diabetes, and incompletely deficient insulin secretion in a case
with type 1 diabetes-resistant human leukocyte antigen DRB1*15:02 treated with
nivolumab.
AB - Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse
effects, especially in the endocrine system. Several cases of acute-onset insulin
dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of
these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1
diabetes, possibly suggesting that HLA might be involved in the onset of diabetes
with anti-PD-1 therapy. We describe an atypical case of hyperglycemia after anti
PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes
and steroid diabetes was given nivolumab three times for chemoresistant
adenocarcinoma of the lung. On day 5 after the third infusion of nivolumab, he
had hyperglycemia (blood glucose 330 mg/dL and hemoglobin A1c 8.0%) without
ketosis and with incompletely deficient insulin secretion. The patient had both
type 1 diabetes susceptible (HLA-A*24:02 and -DRB1*09:01) and resistant (HLA
DRB1*15:02) HLA genotypes. These HLA genotypes differ from those previously
reported in anti-PD-1 antibody-induced diabetes, and might have influenced the
preservation of insulin secretion after nivolumab administration in the present
case.
PMID- 28418117
TI - Articulating the ideal: 50 years of interprofessional collaboration in Medical
Education.
AB - CONTEXT: Health care delivery and the education of clinicians have changed
immensely since the creation of the journal Medical Education. In this project,
we seek to answer the following three questions: How has the concept of
collaboration changed over the past 50 years in Medical Education? Have the
participants involved in collaboration shifted over time? Has the idea of
collaboration itself been transformed over the past 50 years? METHODS: Starting
from a constructionist view of scientific discourse, we used directed content
analysis to sample, code and analyse 144 collaboration-related articles over the
50-year life span of Medical Education. We developed an analytical framework to
identify the key components of varying articulations of 'collaboration', with a
focus on shifts in language and terminology over time. Our sample was drawn from
an archive of 1221 articles developed to celebrate the 50th anniversary of
Medical Education. RESULTS: Interprofessional collaboration is conceptualised in
three primary ways throughout our sample: as a psychometric property; as tasks or
activities, and, more recently, as 'togetherness'. The first conceptualisation
articulates collaboration as involving knowledge or skills that are teachable to
individuals, the second as involving the education of teams to engage in
structured meetings or task distribution, and the third as the building of
networks of individuals who learn to form team identities. The 'leader' of
collaboration is typically conceptualised as the doctor, who is consistently
articulated by authors as the active agent of collaborative care. Other
clinicians and students of other professions are, as the wording in this sentence
suggests, usually positioned as 'others', and thus as more passive participants
in, or even observers of, 'collaboration'. CONCLUSIONS: In order to meet goals of
meaningful collaboration leading to higher-quality care, it behoves us as a
community of educators and researchers to heed the ways in which we teach, think
and write about interprofessional collaboration, interrogating our own language
and assumptions that may be betraying and reproducing harmful care hierarchies.
PMID- 28418118
TI - Enantioselective Heck-Matsuda Arylations through Chiral Anion Phase-Transfer of
Aryl Diazonium Salts.
AB - A mild, asymmetric Heck-Matsuda reaction of five-, six- and seven-membered ring
alkenes and aryl diazonium salts is presented. High yields and
enantioselectivities were achieved using Pd0 and chiral anion co-catalysts, the
latter functioning as a chiral anion phase-transfer (CAPT) reagent. For certain
substrate classes, the chiral anion catalysts were modulated to minimize the
formation of undesired by-products. More specifically, BINAM-derived phosphoric
acid catalysts were shown to prevent alkene isomerization in cyclopentene and
cycloheptene starting materials. DFT(B3LYP-D3) computations revealed that
increased product selectivity resulted from a chiral anion dependent lowering of
the activation barrier for the desired pathway.
PMID- 28418120
TI - Catalytic Enantioselective Synthesis of 2,5-Dihydrooxepines.
AB - A Michael addition initiated cyclopropanation/retro-Claisen rearrangement tandem
reaction was developed for the enantioselective synthesis of highly
functionalized 2,5-dihydrooxepines. In the presence of a chiral oxazaborolidinium
ion (COBI) catalyst, the reaction proceeds to give good yields and high
enantioselectivity.
PMID- 28418119
TI - Endoplasmic reticulum stress pathway PERK-eIF2alpha confers radioresistance in
oropharyngeal carcinoma by activating NF-kappaB.
AB - Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis
and development of malignant tumors, as well as in the regulation of
radiochemoresistance and chemoresistance in many malignancies. ERS signaling
pathway protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic
initiation factor-2 (eIF2alpha) may induce aberrant activation of nuclear factor
kappaB (NF-kappaB). Our previous study showed that NF-kappaB conferred
radioresistance in lymphoma cells. However, whether PERK-eIF2alpha regulates
radioresistance in oropharyngeal carcinoma through NF-kappaB activation is
unknown. Herein, we showed that PERK overexpression correlated with a poor
prognosis for patients with oropharyngeal carcinoma (P < 0.01). Meanwhile, the
percentage of the high expression level of PERK in oropharyngeal carcinoma
patients resistant to radiation was higher than in patients sensitive to
radiation (77.7 and 33.3%, respectively; P < 0.05). Silencing PERK and eIF2alpha
increased the radiosensitivity in oropharyngeal carcinoma cells and increased
radiation-induced apoptosis and G2/M phase arrest. PERK-eIF2alpha silencing also
inhibited radiation-induced NF-kappaB phosphorylation and increased the DNA
double strand break-related proteins ATM phosphorylation. NF-kappaB activator TNF
alpha and the ATM inhibitor Ku55933 offset the regulatory effect of eIF2alpha on
the expression of radiation-induced cell apoptosis-related proteins and the G2/M
phase arrest-related proteins. These data indicate that PERK regulates
radioresistance in oropharyngeal carcinoma through NF-kB activation-mediated
phosphorylation of eIF2alpha, enhancing X-ray-induced activation of DNA DSB
repair, cell apoptosis inhibition and G2/M cell cycle arrest.
PMID- 28418121
TI - The challenge of skin surveillance: observe or biopsy?
PMID- 28418122
TI - The heart of the problem.
PMID- 28418123
TI - Image Gallery: Nicolau syndrome after misuse of buprenorphine.
PMID- 28418124
TI - Image Gallery: Xanthoma tuberosum.
PMID- 28418125
TI - Quantitative risk assessment and the burden of fragrance contact allergy.
PMID- 28418126
TI - Evidence for a biofilm-based treatment strategy in the management of chronic
hidradenitis suppurativa.
PMID- 28418127
TI - Image Gallery: Subcutaneous fat necrosis of the newborn.
PMID- 28418128
TI - Better definition of hidradenitis suppurativa subtypes is needed to progress
disease-specific treatment outcomes.
PMID- 28418129
TI - Ichthyoses: new insights unravel defects in skin barrier function resulting in
diverse clinical and morphological phenotypes.
PMID- 28418130
TI - Image Gallery: Pemphigoid gestationis mimicking a gyrate erythema.
PMID- 28418131
TI - Measuring quality of life in infants, children and adolescents with eczema.
PMID- 28418132
TI - Image Gallery: Immunocompromised patient presenting with inguinal rash: a case of
Scedosporium apiospermum.
PMID- 28418133
TI - Deferoxamine: potential novel topical therapeutic for chronic wounds.
PMID- 28418134
TI - The four Ws of skin cancer surveillance in patients with melanoma: Why? Who?
When? Where?
PMID- 28418135
TI - Cover Image: Are melanocyte-associated peptides the elusive autoantigens in
alopecia areata?
PMID- 28418136
TI - Five-year efficacy of biologics for psoriasis in the real world of daily
practice.
PMID- 28418137
TI - Pregnancy and fetal outcomes after paternal exposure to azathioprine,
methotrexate or mycophenolic acid: a critically appraised topic.
PMID- 28418138
TI - Finding a HOME for outcome measures in atopic dermatitis.
PMID- 28418140
TI - Shedding light on drug photosensitivity reactions.
PMID- 28418141
TI - Image Gallery: Verrucous porokeratosis with characteristic histopathological and
dermoscopic features.
PMID- 28418142
TI - The global burden of diabetic wounds.
PMID- 28418143
TI - Evidence-based medicine for atopic eczema: identifying the knowns and unknowns.
PMID- 28418144
TI - Hand eczema is to be taken seriously ....
PMID- 28418145
TI - Dermatological evaluation in patients with skin of colour: the effect of erythema
on outcome measures in atopic dermatitis.
PMID- 28418149
TI - Image Gallery: Dermoscopy for hair casts due to traction.
PMID- 28418151
TI - Health-related quality of life in hidradenitis suppurativa.
PMID- 28418152
TI - Paternal drug exposure: plenty of confounders, few conclusions.
PMID- 28418153
TI - Image Gallery: A rare abscess-like presentation of Langerhans cell histiocytosis.
PMID- 28418154
TI - Can positron emission tomography (PET) unravel the link between adipose tissue,
vascular inflammation and cardiovascular risk in patients with psoriasis?
PMID- 28418155
TI - Meeting the psychological needs of dermatology patients.
PMID- 28418156
TI - Cutaneous lymphomas in childhood and adolescence: much needed new data.
PMID- 28418157
TI - Effect of canal preparation with TRUShape and Vortex rotary instruments on three
dimensional geometry of oval root canals.
AB - The purpose of this study was to assess the geometry of non-round root canals
after preparation with TRUShape (a novel instrument with s-shaped longitudinal
design) in comparison to conventional rotary instrumentation using micro-computed
tomography. Twenty distal root canals of mandibular molars were randomly
distributed in two groups to be shaped with either TRUShape or Vortex rotaries.
Percentages of unprepared surface and volume of dentin removal for the entire
canal and for the apical 4 mm were calculated. Canal transportation and the
structure model index (SMI) were assessed. Data were compared with Student t
tests. Shaping with both techniques resulted in similar prepared surface and
volume of dentin removed, as well as the extent of canal transportation. The SMI
shape factor was significantly lower for TRUShape preparations (P = 0.04)
suggesting less rounding during rotary preparation. Although both instruments
were suitable for the preparation of oval canals, TRUShape appeared to better
conform to the original ribbon-shaped anatomy.
PMID- 28418158
TI - The phenology of leaf quality and its within-canopy variation is essential for
accurate modeling of photosynthesis in tropical evergreen forests.
AB - Leaf quantity (i.e., canopy leaf area index, LAI), quality (i.e., per-area
photosynthetic capacity), and longevity all influence the photosynthetic
seasonality of tropical evergreen forests. However, these components of tropical
leaf phenology are poorly represented in most terrestrial biosphere models
(TBMs). Here, we explored alternative options for the representation of leaf
phenology effects in TBMs that employ the Farquahar, von Caemmerer & Berry (FvCB)
representation of CO2 assimilation. We developed a two-fraction leaf (sun and
shade), two-layer canopy (upper and lower) photosynthesis model to evaluate
different modeling approaches and assessed three components of phenological
variations (i.e., leaf quantity, quality, and within-canopy variation in leaf
longevity). Our model was driven by the prescribed seasonality of leaf quantity
and quality derived from ground-based measurements within an Amazonian evergreen
forest. Modeled photosynthetic seasonality was not sensitive to leaf quantity,
but was highly sensitive to leaf quality and its vertical distribution within the
canopy, with markedly more sensitivity to upper canopy leaf quality. This is
because light absorption in tropical canopies is near maximal for the entire
year, implying that seasonal changes in LAI have little impact on total canopy
light absorption; and because leaf quality has a greater effect on photosynthesis
of sunlit leaves than light limited, shade leaves and sunlit foliage are more
abundant in the upper canopy. Our two-fraction leaf, two-layer canopy model,
which accounted for all three phenological components, was able to simulate
photosynthetic seasonality, explaining ~90% of the average seasonal variation in
eddy covariance-derived CO2 assimilation. This work identifies a parsimonious
approach for representing tropical evergreen forest photosynthetic seasonality in
TBMs that utilize the FvCB model of CO2 assimilation and highlights the
importance of incorporating more realistic phenological mechanisms in models that
seek to improve the projection of future carbon dynamics in tropical evergreen
forests.
PMID- 28418159
TI - Toxicity of sediment-associated substituted phenylamine antioxidants on the early
life stages of Pimephales promelas and a characterization of effects on
freshwater organisms.
AB - Substituted phenylamine antioxidants (SPAs) are high production volume chemicals
that are incorporated into a variety of commercial products (e.g., polymers,
dyes, lubricants). There are few data on chronic toxicity of SPAs to fish and no
data on the toxicity of SPAs to the early life stages of fish. The
physicochemical properties of SPAs would suggest that if they were to enter an
aquatic ecosystem they would partition into sediment. Therefore, the present
study focused on investigating the chronic effect of sediment-associated SPAs to
the early life stages of the fathead minnow (Pimephales promelas). Eggs and
larvae were exposed to sediment spiked with diphenylamine (DPA), N-phenyl-1
napthylamine (PNA), N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA),
or 4,4'-methylene-bis[N-sec-butylaniline] (MBA). The most sensitive endpoint for
DPA, PNA, and DPPDA was total survival with 21-d median lethal concentrations
(LC50s) based on concentration in overlying water of 1920, 74, and 35 MUg/L,
respectively. The most sensitive endpoint for MBA was growth with a 21-d median
effective concentration (EC50) of 71 MUg/L. The same endpoints were the most
sensitive in terms of concentrations of DPA, PNA, DPPDA, and MBA in sediment
(101, 54, 111, and 76 MUg/g dry wt, respectively). Species sensitivity
distributions (SSDs) were constructed for each SPA based on acute and chronic
toxicity data generated in the present study and found in the literature.
Overall, P. promelas was in the midrange of chronic sensitivity, with the most
sensitive species being Tubifex tubifex. The SSDs indicate that DPA based on
concentration in water is the least toxic to aquatic biota of the 4 SPAs
investigated. The constructed SSDs indicate that a concentration in water and
sediment of 1 MUg/L and 1 MUg/g dry weight, respectively, would be protective of
>95% of the aquatic species tested. Environ Toxicol Chem 2017;36:2730-2738. (c)
2017 SETAC.
PMID- 28418160
TI - Synthesis and Evaluation of 5-(o-Tolyl)-1H-tetrazole Derivatives as Potent
Anticonvulsant Agents.
AB - A series of 5-(o-tolyl)-1H-tetrazole derivatives were synthesized and evaluated
for their anticonvulsant activities. 1-(2-Methylbenzyl)-5-(o-tolyl)-1H-tetrazole
(3h) showed important anticonvulsant activity against the MES-induced seizures,
as well as lower neurotoxicity with an ED50 value of 12.7 mg/kg and a TD50 value
of over 500 mg/kg after intraperitoneal injection into mice, providing 3h with a
high protective index (TD50 /ED50 ) of over 39.4. The achieved results prove that
the distinctive compounds could be valuable as a model for future development,
adaptation, and investigation to construct more active analogues.
PMID- 28418161
TI - Explaining the apparent paradox of persistent selection for early flowering.
AB - Decades of observation in natural plant populations have revealed pervasive
phenotypic selection for early flowering onset. This consistent pattern seems at
odds with life-history theory, which predicts stabilizing selection on age and
size at reproduction. Why is selection for later flowering rare? Moreover,
extensive evidence demonstrates that flowering time can and does evolve. What
maintains ongoing directional selection for early flowering? Several non-mutually
exclusive processes can help to reconcile the apparent paradox of selection for
early flowering. We outline four: selection through other fitness components may
counter observed fecundity selection for early flowering; asymmetry in the
flowering-time-fitness function may make selection for later flowering hard to
detect; flowering time and fitness may be condition-dependent; and selection on
flowering duration is largely unaccounted for. In this Viewpoint, we develop
these four mechanisms, and highlight areas where further study will improve our
understanding of flowering-time evolution.
PMID- 28418162
TI - Exploring the institutional logics of health professions education scholarship
units.
AB - CONTEXT: Although health professions education scholarship units (HPESUs) share a
commitment to the production and dissemination of rigorous educational practices
and research, they are situated in many different contexts and have a wide range
of structures and functions. OBJECTIVES: In this study, the authors explore the
institutional logics common across HPESUs, and how these logics influence the
organisation and activities of HPESUs. METHODS: The authors analysed interviews
with HPESU leaders in Canada (n = 12), Australia (n = 21), New Zealand (n = 3)
and the USA (n = 11). Using an iterative process, they engaged in inductive and
deductive analyses to identify institutional logics across all participating
HPESUs. They explored the contextual factors that influence how these
institutional logics impact each HPESU's structure and function. RESULTS:
Participants identified three institutional logics influencing the organisational
structure and functions of an HPESU: (i) the logic of financial accountability;
(ii) the logic of a cohesive education continuum, and (iii) the logic of academic
research, service and teaching. Although most HPESUs embodied all three logics,
the power of the logics varied among units. The relative power of each logic
influenced leaders' decisions about how members of the unit allocate their time,
and what kinds of scholarly contribution and product are valued by the HPESU.
CONCLUSIONS: Identifying the configuration of these three logics within and
across HPESUs provides insights into the reasons why individual units are
structured and function in particular ways. Having a common language in which to
discuss these logics can enhance transparency, facilitate evaluation, and help
leaders select appropriate indicators of HPESU success.
PMID- 28418163
TI - Psychometric properties of the apathy evaluation scale in patients with
Parkinson's disease.
AB - Parkinson's disease (PD) frequently entails non-motor symptoms, worsening the
course of the disease. Apathy is one of the core neuropsychiatric symptoms that
has been investigated in recent years; research is however hampered by the
limited availability of well-evaluated apathy scales for these patients. We
evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a
sample of PD patients. Psychometric properties, convergent and discriminant
validity and sensitivity/specificity were evaluated in patients with (n = 582) or
without dementia/depression (n = 339). Internal consistency was high in the
entire sample as well as in patients without dementia/depression. Correlations
were moderate for convergent validity (UPDRS I item 4: motivation). While apathy
could be differentiated from cognitive decline, it was related to depression
(Geriatric Depression Scale, GDS-15). The overall classification accuracy based
on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits
good psychometric properties in PD patients with and without dementia and/or
depression. Commonly used screenings on the presence of apathy had low detection
rates compared to the AES and reflected both apathetic and depressive symptoms.
Psychometric evaluation of available instruments will support further research on
the clinical relevance of apathy for disease progression and treatment approaches
in PD patients.
PMID- 28418164
TI - Molecular subtyping of mammary-like adenocarcinoma of the vulva shows molecular
similarity to breast carcinomas.
AB - AIMS: Mammary-like adenocarcinoma (MLA) of the vulva is thought to be derived
from vulvar mammary-like glands. The aim of this study was to characterize a
series of MLAs by using an immunohistochemical algorithm that identifies the
major molecular subtypes of breast cancer. METHODS AND RESULTS: Seven cases of
vulval MLA were stained for oestrogen receptor (ER), progesterone receptor (PR),
human epidermal growth factor receptor 2 (HER2), Ki67, epidermal growth factor
receptor (EGFR), cytokeratin (CK) 5, nestin, and inositol polyphosphate-4
phosphatase (INPP4b). Seventeen cases of vulval extramammary Paget disease
(EMPD), seven with invasion, were studied for comparison. The median age of
patients with MLA was 72 years. All tumours except one were early-stage tumours.
On the basis of an immunohistochemical panel, three of seven tumours were
classified as luminal B, two of seven as HER2-enriched, one of seven as luminal
A, and one of seven as basal-like. ER was expressed in four of seven tumours, PR
in three of seven, HER2 in three of seven, EGFR in two of seven, and CK5 in one
of seven, and the Ki67 index was >15% in six of seven cases. Nestin and INPP4b
were, respectively, negative and positive in all cases. Of the seven cases of
invasive EMPD, two showed a luminal A profile, three a luminal B profile (two of
three with HER2 amplification), one a HER2-enriched profile, and one a basal-like
profile. Three of seven were HER2-amplified. Among the 10 cases of EMPD without
invasion, seven showed a luminal A profile and three showed a luminal B profile
(all HER2-amplified); no HER2-enriched or basal-like subtypes were identified.
CONCLUSIONS: Breast cancer subtyping can be applied to vulvar MLAs. All four
intrinsic molecular subtypes are seen, with frequencies similar to those in
breast carcinoma. Our results support the potential use of breast cancer
molecular profiling algorithms to guide treatment for these cancers.
PMID- 28418165
TI - Physical activities impact sense of coherence among community-dwelling older
adults.
AB - AIM: The objective of the present study was to investigate bidirectional
longitudinal relationships between sense of coherence (SOC) and physical
activities (PA) among community-dwelling older adults. METHODS: Self-administered
questionnaires were sent to 508 community-dwelling adults aged 65-85 years who
expressed their intention to participate in our surveys including cognitive
function tests and physical performance tests. Of these, 427 people responded to
the baseline survey, and 223 of them participated in the follow-up survey 1 year
later. Finally, the number of eligible respondents who had no missing values in
all data was 179 (valid response rate: 35.2%). We used the 13-item five-point
version of the Sense of Coherence Scale to assess SOC variables, and the Physical
Activity Scale for the Elderly to assess PA variables. A structural equation
modeling method was used to analyze bidirectional longitudinal relationships
between SOC and PA. Cross-lagged effects and synchronous effects models were
applied to analyze these relationships. Demographic variables (age, sex,
education, living arrangements, medical histories, employment status), cognitive
function and physical performance were used as control variables. RESULTS:
Leisure-time PA had a cross-lagged effect (beta = 0.117, P < 0.05) and a
synchronous effect (beta = 0.217, P < 0.001) on SOC. In contrast, no significant
effect of SOC on any type of PA was observed in either the cross-lagged effects
model or the synchronous effects model. CONCLUSIONS: Leisure-time PA might
contribute to enhancing SOC in community-dwelling older adults. Geriatr Gerontol
Int 2017; 17: 2208-2215.
PMID- 28418166
TI - Cancer Therapy: Shooting for the Moon.
PMID- 28418170
TI - Possible role of aqueous humour dynamics in Descemet's membrane detachment
resolution.
PMID- 28418171
TI - Formation of oxysterols during thermal processing and frozen storage of cooked
minced meat.
AB - BACKGROUND: Cholesterol is susceptible to oxidation and the formation of
oxysterols, which could have a negative health effect. The formation and
distribution of oxysterols was investigated in meatloaves prepared under
different baking regimes with an increased temperature or prolonged time. The
effect of frozen storage and marjoram addition on the level of oxysterols was
also investigated. RESULTS: The effect of baking regime on the content and
distribution of oxysterols was determined. Temperature was the most important
factor affecting 7-ketocholesterol formation in baked meatloaf. Its content was
significantly higher after baking at 250 degrees C compared to at 180 degrees
C. The content of 7-ketocholesterol increased from the centre (87 ug kg-1 ) to
the surface (122 ug kg-1 ) of baked meatloaves prepared under standard
conditions. The level of alpha-tocopherol and its distribution was also affected
by the baking regime. A higher level of 7-ketocholesterol was found in baked
meatloaves after their frozen storage. The addition of marjoram did not change
this level. CONCLUSION: Inadequate culinary conditions used for preparation of
baked meat can contribute to an increased oxysterol intake in the diet. Frozen
storage did not stop oxysterol formation. The inhibition effect of marjoram on
sterols oxidation was not confirmed. (c) 2017 Society of Chemical Industry.
PMID- 28418172
TI - Analgesic effect of clobazam in chronic low-back pain but not in experimentally
induced pain.
AB - BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the
nervous system, and drugs that increase central inhibition are therefore a
potentially effective treatment. Benzodiazepines are potent modulators of
GABAergic neurotransmission and are known to exert antihyperalgesic effects in
rodents, but translation into patients are lacking. This study investigates the
effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim
of this study is to explore the effect of GABA modulation on chronic low-back
pain and on quantitative sensory tests. METHODS: In this double-blind cross-over
study, 49 patients with chronic low-back pain received a single oral dose of
clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10
numeric rating scale and quantitative sensory tests were assessed during 2 h
after drug intake. RESULTS: Pain intensity in the supine position was
significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs.
3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005).
Pain intensity in the sitting position was not significantly different between
groups. No effects on quantitative sensory tests were observed. CONCLUSIONS: This
study suggests that clobazam has an analgesic effect in patients with chronic low
back pain. Muscle relaxation or sedation may have contributed to the effect.
Development of substances devoid of these side effects would offer the potential
to further investigate the antihyperalgesic action of GABAergic compounds.
SIGNIFICANCE: Modulation of GABAergic pain-inhibitory pathways may be a potential
future therapeutic target.
PMID- 28418173
TI - Rebutting the inclined analyses on the cost-effectiveness and feasibility of
coral reef restoration.
PMID- 28418174
TI - Hypoxia upregulates integrin gene expression in microvascular endothelial cells
and promotes their migration and capillary-like tube formation.
AB - Tissue hypoxia affects gene expression through the hypoxia-inducible
transcription factors, HIF-1 and HIF-2, in both physiological and pathological
angiogenesis. Angiogenesis is a complex response of endothelial cells integrating
cell proliferation, migration, tube formation, and their interaction with the
extracellular matrix through integrin receptors. In this report, we studied the
effect of hypoxia on the angiogenic functions of human microvascular endothelial
cells (HMEC-1) as well as on expression of the angiogenic integrins alphanu beta3
, alphanu beta5 , and alpha5 beta1 . Exposure of HMEC-1 to hypoxia (1% O2 ) or to
DMOG, a prolyl-4-hydroxylase inhibitor, caused significant reduction to their
proliferation rate, whereas their migration ability toward laminin-1 or collagen
IV and capillary-like tube formation were significantly enhanced. In addition,
alphav , beta1 , beta3 , and beta5 integrins expression was increased under
hypoxia in HMEC-1, while alpha5 integrin was not affected. Both HIF-1 and HIF-2
protein expression and transcriptional activity were induced under hypoxia in
HMEC-1. The knockdown of either HIF-1alpha or HIF-2alpha inhibited integrin beta3
hypoxic stimulation, suggesting a HIF-dependent induction of beta3 integrin in
HMEC-1. Taken together, our results indicate that hypoxia transcriptionally up
regulates angiogenic integrins in microvascular endothelial cells along with
promoting migration and tube formation of HMEC-1.
PMID- 28418175
TI - From Bidentate Gallium Lewis Acids to Supramolecular Complexes.
AB - Bidentate gallium Lewis acids were prepared by the reaction of
diethynyldiphenylsilane with neat trimethyl- or triethylgallium.
Bis[(dimethylgallyl)ethynyl]diphenylsilane (1) and diethylgallyl derivative 2
were characterized as Et2 O or pyridine adducts by NMR spectroscopy; 2?2Py was
isolated. Lewis acids 1 and 2 form host-guest adducts with bidentate nitrogen
bases, but defined cyclic 1:1 adducts are only formed between 1 and bases with
matching N???N distances: 4,4'-dimethyl-3,3'-bipyridinylacetylene (3),
bis[(pyridin-3-yl)ethynyl]diphenylsilane (4), and bis[(2-methylpyridin-5
yl)ethynyl]diphenylsilane (5). The structures of adducts 1?3, 1?4, and 1?5 were
established by X-ray diffraction experiments. 2?2Py reacts with DABCO to afford
polymeric (DABCO-2-)n .
PMID- 28418176
TI - Panitumumab-Conjugated Pt-Drug Nanomedicine for Enhanced Efficacy of Combination
Targeted Chemotherapy against Colorectal Cancer.
AB - Targeted combination chemotherapy (TCT) has recently been used to increase the
induction of tumor cell death. In particular, the combination of Panitumumab and
the platinum (Pt)-derived chemotherapeutic drug Oxaliplatin is clinically
effective against KRAS and BRAF wild-type colorectal cancer (CRC) cells that
overexpress epidermal growth factor receptors, and significantly greater efficacy
is observed than with either drug alone. However, low accumulation of Pt drug in
tumor sites prevents achievement of ideal efficacy. To develop an alternative
drug therapy that achieves the ideal efficacy of TCT, the novel nanomedicine
NANOPt-Pan using self-assembled dichloro(1,2-diaminocyclohexane)Pt(II)-modified
Panitumumab is generated. Treatments with NANOPt-Pan lead to significant
accumulation of Pt drug and Panitumumab in tumors, reflecting enhanced
permeability and retention effect, active targeting, and sustained circulation of
the Pt drug in the blood. In addition, NANOPt-Pan has excellent in vivo anti-CRC
efficacy. These data indicate that NANOPt-Pan has high potential as a candidate
nanomedicine for CRC.
PMID- 28418177
TI - Erdheim-Chester disease with unusual clinicopathological features complicated by
DRESS syndrome, disseminated Cytomegalovirus infection and hemophagocytic
lymphohistiocytosis.
PMID- 28418178
TI - Unfolded protein response activation compensates endoplasmic reticulum-associated
degradation deficiency in Arabidopsis.
AB - Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum
(ER) stress. There is a sophisticated ER quality control (ERQC) system to
mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The
accumulation of misfolded proteins in the ER activates the unfolded protein
response (UPR) to enhance ER protein folding and the degradation of misfolded
proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic
stress damage has been well studied in mammals and yeast. However, in plants,
both ERAD and UPR have been studied separately and found to be critical for plant
abiotic stress tolerance. In this study, we discovered that UPR-associated
transcription factors AtbZIP17, AtbZIP28 and AtbZIP60 responded to tunicamycin
(TM) and NaCl induced ER stress and subsequently enhanced Arabidopsis thaliana
abiotic stress tolerance. They regulated the expression level of ER chaperones
and the HRD1-complex components. Moreover, overexpression of AtbZIP17, AtbZIP28
and AtbZIP60 could restore stress tolerance via ERAD in the HRD1-complex mutant
hrd3a-2, which suggested that UPR and ERAD have an interactive mechanism in
Arabidopsis.
PMID- 28418179
TI - Copy number variation, increased gene expression, and molecular mechanisms of
neurofascin in lung cancer.
AB - Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin
(NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and,
while studies on NFASC are inadequate, other members have been indicated pivotal
roles in cancer progression and metastasis. This study aimed at increasing the
knowledge on the involvement of adhesion molecules in lung cancer progression by
studying the regulation and role of NFASC in non-small cell lung cancer (NSCLC).
Here, copy number variations in the NFASC gene were analyzed in tumor and non
tumorous lung tissues of 204 NSCLC patients. Frequent gene amplifications (OR =
4.50, 95%CI: 2.27-8.92, P <= 0.001) and increased expression of NFASC (P = 0.034)
were identified in tumors of NSCLC patients. Furthermore, molecular mechanisms of
NFASC in lung cancer progression were evaluated by investigating the effects of
NFASC silencing on cell proliferation, viability, migration, and invasion using
siRNA technology in four NSCLC cell lines. Silencing of NFASC did not affect cell
proliferation or viability but rather decreased NSCLC cell migration (P <= 0.001)
and led to morphological changes, rearrangements in the actin cytoskeleton and
changes in F-actin networks in migrating NSCLC cell lines. This study is the
first to report frequent copy number gain and increased expression of NFASC in
NSCLC. Moreover, these data suggest that NFASC is a novel regulator of NSCLC cell
motility and support a role of NFASC in the regulation of NSCLC progression.
PMID- 28418181
TI - Alibis: Generation, Consistency, Corroboration, Believability, and Detection -
Introduction to this Special Issue.
AB - This special issue highlights recent developments in the field of alibi research.
These include a shift from self-report studies to behavioral paradigms; a
broadening in the literature to study not only suspects, investigators, and legal
decision makers, but also alibi corroborators; and an expansion of the research
to include alibi-related memory issues rather than a sole focus on social impact
factors. Additionally, this special issue addresses the many misconceptions that
exist when it comes to the appraisal of consistency in the context of alibi
accuracy and truthfulness. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28418180
TI - "Little things matter!" Exploring the perspectives of patients with dementia
about the hospital environment.
AB - BACKGROUND: Recognising demographic changes and importance of the environment in
influencing the care experience of patients with dementia, there is a need for
developing the knowledge base to improve hospital environments. Involving
patients in the development of the hospital environment can be a way to create
more responsive services. To date, few studies have involved the direct voice of
patients with dementia about their experiences of the hospital environment.
DESIGN AND METHOD: Using an action research approach, we worked with patients
with dementia and a team of interdisciplinary staff on a medical unit to improve
dementia care. The insights provided by patients with dementia in the early phase
shaped actions undertaken at the later stage to develop person-centred care
within a medical ward. We used methods including go-along interviews, video
recording and participant observation to enable rich data generation. AIM: This
study explores the perspectives of patients with dementia about the hospital
environment. RESULTS: The participants indicated that a supportive hospital
environment would need to be a place of enabling independence, a place of safety,
a place of supporting social interactions and a place of respect. CONCLUSIONS:
Patient participants persuasively articulated the supportive and unsupportive
elements in the environment that affected their well-being and care experiences.
They provided useful insights and pointed out practical solutions for
improvement. Action research offers patients not only opportunities to voice
their opinion, but also possibilities to contribute to hospital service
development. IMPLICATIONS FOR PRACTICE: This is the first study that demonstrates
the possibility of using go-along interviews and videoing with patients with
dementia staying in a hospital for environmental redesign. Researchers, hospital
leaders and designers should further explore strategies to best support the
involvement of patients with dementia in design and redesign of hospital
environments.
PMID- 28418182
TI - Cyclometalated Iridium(III) Bipyridine-Phenylboronic Acid Complexes as Bioimaging
Reagents and Luminescent Probes for Sialic Acids.
AB - Sialic acids play important roles in mammalian development, cell-cell attachment,
and signaling. As cancer cells utilize their overexpressed sialylated antigens to
propagate metastases, the development of probes for sialic acids is of high
importance. Herein, we report three luminescent cyclometalated iridium(III)
bipyridine complexes bearing a phenylboronic acid (PBA) moiety.
Spectrophotometric titrations revealed that the PBA complexes displayed higher
binding affinity for the most common sialic acid N-acetylneuraminic acid (Neu5Ac)
compared with simple sugars that are commonly found on glycoproteins. Notably,
cellular imaging and uptake experiments showed that the PBA complexes were able
to recognize cellular sialic acid residues, resulting in more efficient uptake
than the boronic acid-free analogs. Additionally, one of the PBA complexes was
shown to discriminate between cancerous and noncancerous cells.
PMID- 28418184
TI - B(C6 F5 )3 -Catalyzed Cascade Reduction of Pyridines.
AB - B(C6 F5 )3 has been found to be an effective catalyst for reduction of pyridines
and other electron-deficient N-heteroarenes with hydrosilanes (or hydroboranes)
and amines as the reducing reagents. The success of this development hinges upon
the realization of a cascade process of dearomative hydrosilylation (or
hydroboration) and transfer hydrogenation. The broad functional-group tolerance
(e.g. ketone, ester, unactivated olefins, nitro, nitrile, heterocycles, etc.)
implies high practical utility.
PMID- 28418183
TI - Evaluation of gender-based disparities in time from initial haematuria
presentation to upper tract urothelial carcinoma diagnosis: analysis of a
nationwide insurance claims database.
AB - OBJECTIVE: To investigate the length of time from initial haematuria presentation
to upper tract urothelial carcinoma (UTUC) diagnosis and the effect of gender on
this duration. PATIENTS AND METHODS: Patients with haematuria claims in the year
prior to UTUC diagnosis were identified from the MarketScan database (2010-2014).
Delayed diagnosis was defined as >90 days from haematuria presentation to UTUC
diagnosis. Multivariable Poisson regression models were used to determine factors
associated with delayed UTUC diagnosis. RESULTS: Among 1 326 patients with UTUC,
469 (35.4%) experienced delayed diagnosis. Men (n = 866) had a longer median
interval from haematuria to diagnosis than women (60 vs 49 days; P = 0.04). In
the multivariable model, male gender (relative risk [RR] 1.13, 95% confidence
interval [CI] 0.95-1.34) was not associated with delayed diagnosis, while urinary
tract infection (UTI; RR 1.52, 95% CI 1.32-1.76), nephrolithiasis (RR 1.23, 95%
CI 1.06-1.44), new (RR 1.37, 95% CI 1.12-1.66) and recurrent prostate-related
diagnoses (RR 1.61, 95% CI 1.23-2.10) were. For men presenting to non-urologists,
UTI (RR 1.44, 95% CI 1.22-1.71), nephrolithiasis (RR 1.25 95% CI 1.05-1.49), new
(RR 1.41, 95% CI 1.12-1.78) and recurrent prostate-related diagnoses (RR 1.94,
95% CI 1.45-2.58) were associated with delayed diagnosis; however, for men
presenting to urologists, nephrolithiasis (RR 1.08 95% CI 0.78-1.49), new (RR
1.15, 95% CI 0.79-1.68) and recurrent prostate-related diagnoses (RR 1.17, 95% CI
0.69-1.97) were not associated with delayed diagnosis, while UTI diagnosis (RR
1.74, 95% CI 1.31-2.31) was still associated with delayed diagnosis. CONCLUSION:
A UTUC diagnosis was made >90 days after haematuria presentation in approximately
one-third of patients. Men experienced a longer median interval from haematuria
to UTUC diagnosis compared with women, but male gender was not an independent
predictor of delayed diagnosis. Benign diagnoses during haematuria evaluation
were strongly associated with delayed diagnosis, especially among patients
initially seen by non-urologists. Future interventions should focus on
development of non-invasive techniques to improve clinical risk stratification of
patients presenting with haematuria and to educate practitioners, especially non
urologists, with regard to the importance of a thoughtful haematuria evaluation
and the common mimickers of UTUC, to help reduce delays in diagnosis.
PMID- 28418185
TI - Cu/Pd Synergistic Dual Catalysis: Asymmetric alpha-Allylation of an alpha-CF3
Amide.
AB - Despite the burgeoning demand for fluorine-containing chemical entities, the
construction of CF3 -containing stereogenic centers has remained elusive. Herein,
we report the strategic merger of CuI /base-catalyzed enolization of an alpha-CF3
amide and Pd0 -catalyzed allylic alkylation in an enantioselective manner to
deliver chiral building blocks bearing a stereogenic carbon center connected to a
CF3 , an amide carbonyl, and a manipulable allylic group. The phosphine complexes
of CuI and Pd0 engage in distinct catalytic roles without ligand scrambling to
render the dual catalysis operative to achieve asymmetric alpha-allylation of the
amide. The stereoselective cyclization of the obtained alpha-CF3 -gamma,delta
unsaturated amides to give tetrahydropyran and gamma-lactone-fused cyclopropane
skeletons highlights the synthetic utility of the present catalytic method as a
new entry to non-racemic CF3 -containing compounds.
PMID- 28418186
TI - A Multifunctional Tb-MOF for Highly Discriminative Sensing of Eu3+ /Dy3+ and as a
Catalyst Support of Ag Nanoparticles.
AB - Exploring novel multifunctional rare earth materials is very important because
these materials have fundamental interests, such as new structural facts and
connecting modes, as well as potential technological applications, including
optics, magnetic properties, sorption, and catalytic behaviors. Especially,
employing these nanomaterials for sensing or catalytic reactions is still very
challenging. Herein, a new superstable, anionic terbium-metal-organic-framework,
[H2 N(CH3 )2 ][Tb(cppa)2 (H2 O)2 ], (China Three Gorges University (CTGU-1), H2
cppa = 5-(4-carboxyphenyl)picolinic acid), is successfully prepared, which can be
used as a turn-on, highly-sensitive fluorescent sensor to detect Eu3+ and Dy3+ ,
with a detection limitation of 5 * 10-8 and 1 * 10-4 m in dimethylformamide,
respectively. This result represents the first example of lanthanide-metal
organic-frameworks (Ln-MOF) that can be employed as a discriminative fluorescent
probe to recognize Eu3+ and Dy3+ . In addition, through ion exchanging at room
temperature, Ag(I) can be readily reduced in situ and embedded in the anionic
framework, which leads to the formation of nanometal-particle@Ln-MOF composite
with uniform size and distribution. The as-prepared Ag@CTGU-1 shows remarkable
catalytic performance to reduce 4-nitrophenol, with a reduction rate constant
kappa as large as 2.57 * 10-2 s-1 ; almost the highest value among all reported
noble-metal-nanoparticle@MOF composites.
PMID- 28418187
TI - Author response to "Letter to Editor by Roger Mepsted".
PMID- 28418188
TI - A Facile and Versatile Synthesis of Energetic Furazan-Functionalized 5-Nitroimino
1,2,4-Triazoles.
AB - An analogue-oriented synthetic route for the formulation of furazan
functionalized 5-nitroimino-1,2,4-triazoles has been explored. The process was
found to be straightforward, high yielding, and highly efficient, and scalable.
Nine compounds were synthesized and the physicochemical and energetic properties,
including density, thermal stability, and sensitivity, were investigated, as well
as the energetic performance (e.g., detonation velocities and detonation
pressures) as evaluated by using EXPLO5 code. Among the new materials, compounds
4-6 and 11 possess high densities, acceptable sensitivities, and good detonation
performances, and thereby demonstrate the potential applications as new secondary
explosives.
PMID- 28418189
TI - Epileptic manifestations in stroke patients treated with intravenous alteplase.
AB - BACKGROUND AND PURPOSE: Intravenous alteplase (rtPA) may be associated with
seizures and epileptic activity in the electroencephalogram (EEG). The aim of
this work was to compare the frequency of seizures and EEG abnormalities between
stroke patients treated and not treated with rtPA. METHODS: This was a
prospective study of consecutive acute anterior circulation ischaemic stroke
patients, with 1-year follow-up. Patients were previously independent, had an
admission National Institute of Health Stroke Scale score >=4, an acute ischaemic
lesion and no previous seizures. They received standardized diagnostic and
medical care. A video-EEG was performed in 72 h (first EEG); during admission
(daily until day 7 and after that if neurological worsening); at discharge and 1
year after stroke. RESULTS: In all, 151 patients (101 treated with rtPA) were
included. The frequency of acute and remote symptomatic seizures was not
significantly different between rtPA treated and non-treated patients (P = 0.726
and P = 0.748, respectively). Clinical paroxysmal phenomena during rtPA perfusion
were observed in five (5%) patients. In the first EEG, rtPA treated patients more
often had background diffuse slowing (43.6% vs. 26.0%, P = 0.036). This
difference was no longer observed at discharge (24.0% vs. 19.1%, P = 0.517) nor 1
year after (11.8% vs. 10.0%, P = 0.765). No differences were found in the
frequency of epileptiform (P = 0.867) or periodic discharges (P = 0.381).
CONCLUSIONS: Intravenous alteplase is not associated with an increased risk of
clinical or electroencephalographic epileptic phenomena.
PMID- 28418190
TI - Strategic Shuffling of Clay Layers to Imbue Them with Responsiveness.
AB - Layers of naturally occurring clay minerals are rearranged to prepare highly
sensitive multiresponsive clay-clay bilayer membrane (CCBM). The CCBM introduced
here responds to the minuscule changes in the surrounding environments including
temperature, humidity, and presence of solvent vapors by morphing in specific
manners. Strips cut from CCBM exhibit up to 588 N kg-1 force output when exposed
to temperature fluctuations. Inheriting the natural stability of clay minerals,
CCBM demonstrates extreme robustness, heating up to 500 degrees C, cooling with
liquid N2 and exposure to corrosive chemical vapors did not deteriorate its
bending performance. Mechanistic studies suggest that shape transformations of
CCBM are driven by the unequal response of its components to external stimuli.
PMID- 28418191
TI - Evaluation of the Chinese herbal medicine Jinlida in type 2 diabetes patients
based on stratification: Results of subgroup analysis from a 12-week trial.
AB - BACKGROUND: The Chinese herbal medicine Jinlida can significantly enhance the
hypoglycemic action of metformin. However, the population showing the best
responses to Jinlida has not been clarified. The aim of the present study was to
compare the efficacy of Jinlida in type 2 diabetes mellitus (T2DM) after
stratification. METHODS: Data were analyzed from a 12-week randomized placebo
controlled double-blind multicenter study with 192 T2DM patients (186 completed
the study). The efficacy evaluation included HbA1c, fasting plasma glucose (FPG),
and 2-h postprandial glucose (2hPG) levels stratified by baseline HbA1c, sex,
age, body mass index (BMI), and duration of T2DM diagnosis. Homeostasis model
assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of
beta-cell function (HOMA-beta) were also evaluated stratified by baseline insulin
levels. RESULTS: In the Jinlida group, HbA1c was significantly reduced (P <
0.05). Greater reductions were observed in patients with baseline HbA1c >8.5%, in
males and in those aged >60 years, with a BMI <=24 kg/m2 , or with a duration of
T2DM diagnosis >5 years (P < 0.05). Compared with baseline, Jinlida significantly
alleviated insulin resistance (P < 0.05) in patients with baseline insulin levels
>20 mU/L. Jinlida also significantly improved beta-cell function in patients with
baseline insulin levels <=20 mU/L (P < 0.05). CONCLUSIONS: Jinlida significantly
improved glycemic control, with greater improvements in patients with poor
glycemic control and male, elderly, of normal weight, or with a long disease
course. Furthermore, Jinlida alleviated insulin resistance with hyperinsulinemia
and promoted insulin secretion with hypoinsulinemia. These results need to be
further confirmed in clinical trials.
PMID- 28418193
TI - Highly Efficient Carbon Dioxide Hydrogenation to Methanol Catalyzed by Zigzag
Platinum-Cobalt Nanowires.
AB - Carbon dioxide (CO2 ) hydrogenation is an effective strategy for CO2 utilization,
while unsatisfied conversion efficiencies remain great challenges. It is reported
herein that zigzag Pt-Co nanowires (NWs) with Pt-rich surfaces and abundant
steps/edges can perform as highly active and stable CO2 hydrogenation catalysts.
It is found that tuning the Pt/Co ratio of the Pt-Co NWs, solvents, and catalyst
supports could well optimize the CO2 hydrogenation to methanol (CH3 OH) with the
Pt4 Co NWs/C exhibiting the best performance, outperforming all the previous
catalysts. They are also very durable with limited activity decays after six
catalytic cycles. The diffuse reflectance infrared Fourier transform spectroscopy
result of CO2 adsorption shows that the Pt4 Co NWs/C undergoes the
adsorption/activation of CO2 by forming appropriate carboxylate intermediates,
and thus enhancing the CH3 OH production.
PMID- 28418194
TI - Accelerated tumour metastasis due to interferon-gamma receptor-mediated
dissociation of perivascular cells from blood vessels.
AB - Angiostasis mediated by interferon (IFN)-gamma is a key mechanism of anti-tumour
immunity; however, the effect of IFN-gamma on host vascular endothelial growth
factor A (VEGFA)-expressing cells during tumour progression is still elusive.
Here, we developed transgenic mice with IFN-gamma receptor (IFNgammaR) expression
under control of the Vegfa promoter (V-gammaR). In these mice, the IFN-gamma
responsiveness of VEGFA-expressing cells led to dramatic growth suppression of
transplanted lung carcinoma cells. Surprisingly, increased mortality and tumour
metastasis were observed in the tumour-bearing V-gammaR mice, in comparison with
the control wild-type and IFNgammaR-deficient mice. Further study showed that
perivascular cells were VEGFA-expressing cells and potential IFN-gamma targets.
In vivo, tumour vascular perfusion and pericyte association with blood vessels
were massively disrupted in V-gammaR mice. In vitro, IFN-gamma inhibited
transforming growth factor-beta signalling by upregulating SMAD7, and therefore
downregulated N-cadherin expression in pericytes. Importantly, IFN-gamma
neutralization in vivo with a monoclonal antibody reduced tumour metastasis.
Together, the results suggest that IFNgammaR-mediated dissociation of
perivascular cells from blood vessels contributes to the acceleration of tumour
metastasis. Thus, the inhibition of tumour growth via IFN-gamma-induced
angiostasis might also accelerate tumour metastasis. Copyright (c) 2017
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28418192
TI - Detection of potentially novel paramyxovirus and coronavirus viral RNA in bats
and rats in the Mekong Delta region of southern Viet Nam.
AB - Bats and rodents are being increasingly recognized as reservoirs of emerging
zoonotic viruses. Various studies have investigated bat viruses in tropical
regions, but to date there are no data regarding viruses with zoonotic potential
that circulate in bat and rat populations in Viet Nam. To address this paucity of
data, we sampled three bat farms and three wet markets trading in rat meat in the
Mekong Delta region of southern Viet Nam. Faecal and urine samples were screened
for the presence of RNA from paramyxoviruses, coronaviruses and filoviruses.
Paramyxovirus RNA was detected in 4 of 248 (1%) and 11 of 222 (4.9%) bat faecal
and urine samples, respectively. Coronavirus RNA was detected in 55 of 248 (22%)
of bat faecal samples; filovirus RNA was not detected in any of the bat samples.
Further, coronavirus RNA was detected in 12 of 270 (4.4%) of rat faecal samples;
all samples tested negative for paramyxovirus. Phylogenetic analysis revealed
that the bat paramyxoviruses and bat and rat coronaviruses were related to
viruses circulating in bat and rodent populations globally, but showed no cross
species mixing of viruses between bat and rat populations within Viet Nam. Our
study shows that potentially novel variants of paramyxoviruses and coronaviruses
commonly circulate in bat and rat populations in Viet Nam. Further
characterization of the viruses and additional human and animal surveillance is
required to evaluate the likelihood of viral spillover and to assess whether
these viruses pose a risk to human health.
PMID- 28418195
TI - Association between type 2 diabetes, curative treatment and survival in men with
intermediate- and high-risk localized prostate cancer.
AB - OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was
received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as
little is known about the influence of T2DM diagnosis on the receipt of such
treatment in men with localized PCa. SUBJECTS AND METHODS: The Prostate Cancer
database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n =
2210) for comparison with data on men with PCa only (n = 23 071). All men had
intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20
ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL)
localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate
logistic regression was used to calculate the odds ratios (ORs) for receipt of
curative treatment in men with and without T2DM. Overall survival, for up to 8
years of follow-up, was calculated both for men with T2DM only and for men with
T2DM and PCa. RESULTS: Men with T2DM were less likely to receive curative
treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69
0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and
high-risk PCa who did and did not receive curative treatment, respectively.
CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for
localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who
received curative treatment had substantially higher survival times than those
who did not. Some of the survival differences represent a selection bias, whereby
the healthiest patients received curative treatment. Clinicians should interpret
this data carefully and ensure that individual patients with T2DM and PCa are not
under- nor overtreated.
PMID- 28418196
TI - Clinical frailty is independently associated with non-prescription of
anticoagulants in older patients with atrial fibrillation.
AB - AIM: Anticoagulants are underused in older patients with atrial fibrillation
(AF). Scoring systems, such as CHA2 DS2 -VASc and HAS-BLED, are recommended to
guide clinicians in anticoagulation decisions, but patients' frailty might be an
underrecognized factor. We investigated the association between the Clinical
Frailty Scale (CFS) and community anticoagulant prescribing habits in patients
aged >=75 years with AF admitted acutely to hospital. METHODS: Data were gathered
retrospectively over 3 months on individuals admitted under a medical team to a
tertiary teaching hospital in the UK. Demographics, AF history, CHA2 DS2- VASc,
HAS-BLED and CFS were collected. Bivariable analysis compared anticoagulated and
non-anticoagulated groups. Each component of the CHA2 DS2 -VASc and HAS-BLED
scores, as well as frailty, age and sex, were entered in a multivariable
analysis. RESULTS: A total of 419 patients with known AF were included. Of these,
215 were not anticoagulated (51.3%) on admission. Non-anticoagulated individuals
were older (median age 87 years, [interquartile range (IQR) 7] vs 83 years [IQR
6], P < 0.001), more likely to be frail (81.4% vs 52.5%, P < 0.001) and had lower
CHA2 DS2 -VASc scores (median 4, [IQR 2] vs 5 [IQR 2], P = 0.01). In the
multivariable analysis, frailty had the strongest effect against anticoagulant
prescription (OR 0.77, 95% CI 0.70-0.85, P < 0.001) compared with other
significant risk factors, such as age (OR 0.98, 95% CI 0.97-0.98, P < 0.001) and
bleeding risk (OR 0.85, 95% CI 0.74-0.97, P = 0.02). CONCLUSIONS: Frailty is
associated with non-prescription of anticoagulants, independently of CHA2 DS2
VASc and HAS-BLED. It could be an important unmeasured factor in anticoagulation
decisions. The utility of explicit frailty measurements in anticoagulation
decisions and patient outcomes requires further research. Geriatr Gerontol Int
2017; 17: 2178-2183.
PMID- 28418197
TI - Body mass index associates with white matter microstructure in bipolar
depression.
AB - OBJECTIVES: Obesity has been reported in over 60% of bipolar disorder (BD)
patients. It worsens the severity of illness, and influences cognition and
functional outcomes. White matter (WM) abnormalities are one of the most
consistently reported findings in neuroimaging studies of BD. We hypothesized
that body mass index (BMI) could correlate with WM integrity in bipolar patients.
METHODS: We evaluated BMI in a sample of 164 depressed patients affected by BD.
We performed whole-brain tract-based spatial statistics with threshold-free
cluster enhancement for the diffusion tensor imaging (DTI) measures of WM
integrity: fractional anisotropy; axial, radial, and mean diffusivity. RESULTS:
We observed that BMI was associated with DTI measures of WM integrity in several
fiber tracts: anterior corona radiata, anterior thalamic radiation, inferior
fronto-occipital fasciculus and corpus callosum. CONCLUSIONS: The association of
BMI in key WM tracts that are crucial to mood regulation and neurocognitive
functioning suggests that BMI might contribute to the pathophysiology of BD
through a detrimental action on structural connectivity in critical cortico
limbic networks.
PMID- 28418198
TI - Stress is associated with an increased risk of recurrent seizures in adults.
AB - OBJECTIVE: The literature is sparse on the complex interrelationships between
stressors, depression, anxiety disorders, and epilepsy. We hypothesized that a
relationship exists between stress and epilepsy. We evaluated whether markers of
stress are associated with seizure recurrence in a low income community-based
cohort of adults with single unprovoked seizure or newly diagnosed epilepsy.
METHODS: We ascertained adult residents of Northern Manhattan and Harlem, New
York City, with a first unprovoked seizure or newly diagnosed epilepsy, between
December 2010 and January 2013. At enrollment, we collected information about
seizure phenomenology, demographics, clinical information, and measures of stress
(environmental stress, stressful life events, facets of allostatic load-i.e., the
cumulative effect of adaptation to stress, psychiatric disorders, and low
collective efficacy). Collective efficacy assesses neighborhood characteristics
and incorporates social cohesion and informal social control. All subjects were
followed for 2 years for further seizures. Cox proportional hazard regression
models were used to estimate the hazard ratios of seizure recurrence during the 2
years of follow-up. RESULTS: We identified 52 subjects (64.2%) with a single
unprovoked seizure and 29 (35.9%) with newly diagnosed epilepsy. Seizure
recurrence was recorded in 38.5% (N = 20) of subjects with a single unprovoked
seizure and in 69% of those with epilepsy (N = 20) (p = 0.01). In the overall
sample, the hazard of seizure recurrence was increased by lifetime generalized
anxiety disorder (3.0-fold) and by low collective efficacy (2.7-fold). In a
second model, the hazard was increased by lifetime mood disorder (2.1-fold) and
low collective efficacy (2.5-fold). SIGNIFICANCE: Markers of stress (i.e., low
collective efficacy, lifetime mood disorder, and lifetime generalized anxiety
disorder) were associated with an increased risk for seizure recurrence in adults
with a single unprovoked seizure or newly diagnosed epilepsy. Stress-reducing
interventions, such as mindfulness, may be a useful, safe, and inexpensive
adjunctive treatment for epilepsy.
PMID- 28418200
TI - Lewis Acid Promoted Single C-F Bond Activation of the CF3 Group: SN 1'-Type 3,3
Difluoroallylation of Arenes with 2-Trifluoromethyl-1-alkenes.
AB - Activation of the sp3 C-F bond in 2-trifluoromethyl-1-alkenes was accomplished
through treatment with a Lewis acid. In the presence of an equimolar amount of
EtAlCl2 , the (trifluoromethyl)alkenes readily underwent an SN 1'-type reaction
with arenes through a Friedel-Crafts-type mechanism via elimination of a fluoride
ion to afford 3,3-difluoroallylated arenes in good yields. This selective
activation of one C-F bond of the CF3 group provides a synthetic method for
accessing biologically and synthetically important 1,1-difluoro-1-alkenes.
PMID- 28418199
TI - Evaluation of Biological Activity and Computer-Aided Design of New Soft
Glucocorticoids.
AB - Soft glucocorticoids are compounds that are biotransformed to inactive and non
toxic metabolites and have fewer side effects than traditional glucocorticoids. A
new class of 17beta-carboxamide steroids has been recently introduced by our
group. In this study, local anti-inflammatory activity of these derivatives was
evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with
the highest maximal edema inhibition (MEI) were pointed out, and the systemic
side effects of those with the lowest EC50 values were significantly lower in
comparison to dexamethasone. A 3D-QSAR model was created and employed for the
design of 27 compounds. By use of the sequential combination of ligand-based and
structure-based virtual screening, three compounds were selected from the ChEMBL
library and used as a starting point for the design of 15 derivatives. Molecular
docking analysis of the designed derivatives with the highest predicted MEI and
relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7,
VS13, and VS14) confirmed the presence of interactions with the glucocorticoid
receptor that are important for the activity.
PMID- 28418201
TI - Chemoinformatics at IFP Energies Nouvelles: Applications in the Fields of Energy,
Transport, and Environment.
AB - The objective of the present paper is to summarize chemoinformatics based
research, and more precisely, the development of quantitative structure property
relationships performed at IFP Energies nouvelles (IFPEN) during the last decade.
A special focus is proposed on research activities performed in the
"Thermodynamics and Molecular Simulation" department, i. e. the use of multiscale
molecular simulation methods in responses to projects. Molecular simulation
techniques can be envisaged to supplement dataset when experimental information
lacks, thus the review includes a section dedicated to molecular simulation
codes, development of intermolecular potentials, and some of their possible
applications. Know-how and feedback from our experiences in terms of machine
learning application for thermophysical property predictions are included in a
section dealing with methodological aspects. The generic character of
chemoinformatics is emphasized through applications in the fields of energy,
transport, and environment, with illustrations for three IFPEN business units:
"Transports", "Energy Resources", and "Processes". More precisely, the review
focus on different challenges such as the prediction of properties for
alternative fuels, the prediction of fuel compatibility with polymeric materials,
the prediction of properties for surfactants usable in chemical enhanced oil
recovery, and the prediction of guest-host interactions between gases and
nanoporous materials in the frame of carbon dioxide capture or gas separation
activities.
PMID- 28418202
TI - Benzodioxole-Pyrazole Hybrids as Anti-Inflammatory and Analgesic Agents with COX
1,2/5-LOX Inhibition and Antioxidant Potential.
AB - Two series of benzodioxole-pyrazole hybrids were synthesized and the IC50 values
for in vitro inhibition of the enzymes cyclooxygenase 1/2 (COX-1, COX-2) and 5
lipoxygenase (5-LOX) were investigated. All compounds were tested for their in
vivo anti-inflammatory and analgesic potentials using diclofenac sodium as a
reference standard. Compounds 4, 11, 17, 20, 21, 26, and 27, which showed good
analgesic and/or anti-inflammatory activities, were also evaluated for their
ability to inhibit tumor necrosis factor (TNF)-alpha production, myeloperoxidase
and proteinase, beside their antioxidant activity. Collectively, compounds 11,
17, and 26 displayed significant anti-inflammatory, analgesic, and antioxidant
activities, beside dual COX-2 and 5-LOX inhibition. Among these, compound 26
showed high selectivity for in vitro COX-1/COX-2 inhibition, whereas the analogs
11 and 17 noticeably ameliorated the TNF-alpha level by 85.19 and 97.71%,
respectively. A molecular docking study was performed to investigate the possible
binding mode of compounds 11, 17, and 26 with the active sites of the COX-2 and 5
LOX enzymes, where they showed nearly the same binding pattern as that of
celecoxib and meclofenamic acid, respectively.
PMID- 28418203
TI - Effectiveness of vildagliptin as add-on to metformin monotherapy among
uncontrolled type 2 diabetes mellitus patients in a real-world setting.
AB - BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a
dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the
treatment of type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with
vildagliptin and metformin has been established in randomized controlled trials,
but there is little evidence from observational studies. The aims of the present
study were to evaluate the effectiveness of vildagliptin as an add-on therapy to
metformin in reducing HbA1c and its affects on body weight and blood lipids in a
real-life setting. METHODS: Included in the present retrospective cohort were
T2DM patients (n = 345) who were uncontrolled on metformin monotherapy and
intensified treatment with vildagliptin. The efficacy of at least 90 days of dual
therapy with vildagliptin and metformin in reducing HbA1c levels, as well as
changes in blood lipids and body weight, were evaluated. RESULTS: After 180 days
(range 90-365 days) from the index date with a mean daily dose of 92 mg
vildagliptin, HbA1c was significantly (P < 0.001) reduced by an average of 0.9%
(95% confidence interval -1.0%, -0.7%). The absolute reduction in HbA1c was
positively associated with baseline HbA1c levels. In addition to HbA1c, a modest
but significant (P < 0.05) decrement was also calculated in the patients' body
weight and blood lipids. CONCLUSIONS: The present analysis of real-world data
corroborates the results of previous randomized controlled trials indicating that
add-on therapy with vildagliptin in uncontrolled patients on metformin
monotherapy is associated with a significant improvement in the control of HbA1c.
PMID- 28418204
TI - Modeling aesthetics to support an ecosystem services approach for natural
resource management decision making.
AB - This paper reviews literature on aesthetics and describes the development of
vista and landscape aesthetics models. Spatially explicit variables were chosen
to represent physical characteristics of natural landscapes that are important to
aesthetic preferences. A vista aesthetics model evaluates the aesthetics of
natural landscapes viewed from distances of more than 1000 m, and a landscape
aesthetics model evaluates the aesthetic value of wetlands and forests within
1000 m from the viewer. Each of the model variables is quantified using spatially
explicit metrics on a pixel-specific basis within EcoAIMTM, a geographic
information system (GIS)-based ecosystem services (ES) decision analysis support
tool. Pixel values are "binned" into ranked categories, and weights are assigned
to select variables to represent stakeholder preferences. The final aesthetic
score is the weighted sum of all variables and is assigned ranked values from 1
to 10. Ranked aesthetic values are displayed on maps by patch type and integrated
within EcoAIM. The response of the aesthetic scoring in the models was tested by
comparing current conditions in a discrete area of the facility with a
Development scenario in the same area. The Development scenario consisted of two
6-story buildings and a trail replacing natural areas. The results of the vista
aesthetic model indicate that the viewshed area variable had the greatest effect
on the aesthetics overall score. Results from the landscape aesthetics model
indicate a 10% increase in overall aesthetics value, attributed to the increase
in landscape diversity. The models are sensitive to the weights assigned to
certain variables by the user, and these weights should be set to reflect
regional landscape characteristics as well as stakeholder preferences. This
demonstration project shows that natural landscape aesthetics can be evaluated as
part of a nonmonetary assessment of ES, and a scenario-building exercise provides
end users with a tradeoff analysis in support of natural resource management
decisions. Integr Environ Assess Manag 2017;13:926-938. (c) 2017 SETAC.
PMID- 28418205
TI - It's not just what you know: junior trainees' approach to follow-up and
documentation.
AB - CONTEXT: In teaching hospitals, junior trainees (first-year residents and third
year medical students) are responsible for patient follow-up and documentation
under the supervision of senior team members. In order to support trainees in
their role, supervisors need to understand how trainees approach these tasks and
how they can be coached to develop best practices. OBJECTIVES: The purpose of our
study was to explore the range of practices used by junior trainees in clinical
settings. METHODS: Constructivist grounded theory was used to guide the
collection and analysis of data on follow-up and documentation during 34
observation periods with 17 junior trainees. Data sources included field notes,
field interviews and de-identified copies of patient charts. We also held two
focus groups with four attending physicians in each. RESULTS: We were able to
describe three interrelated characteristics that influenced a trainee's approach
to and ability to perform the tasks of patient follow-up and documentation: (i)
diligence; (ii) relationship to the team (dependent, independent, collaborative),
and (iii) level of performance (Data Gatherer, Sensemaker, Manager). Diligence
and relationship to the team appeared to influence the quality and focus of a
trainee's approach at all levels of performance. Level of performance was felt,
by focus group attending physicians, to reflect a developmental progression of
knowledge and skills. CONCLUSIONS: Our findings contribute to the existing
literature in three ways. Firstly, they extend our understanding of how junior
trainees approach the task of in-patient follow-up and clinical documentation and
the value of those activities. Secondly, they provide new insights to support
formative and summative assessment. Finally, they contribute to a growing body of
literature exploring the factors that impact trainees' roles and interactions
with the team. Future research should focus on validating our findings and
exploring their utility in the development of novel assessment strategies.
PMID- 28418206
TI - Anti-NMDA-receptor encephalitis during pregnancy: A case report and literature
review.
AB - Anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is an autoimmune
disorder that was first described by Dr Vitaliani in 2005. In 2007, Dalmau et al.
found anti-NMDA-R antibody expressed both in the hippocampus and prefrontal nerve
cell membrane, finally proposing the diagnosis of autoimmune anti-NMDA-R
encephalitis. Most of the patients are female (91%), with ages ranging from 4 to
76 years. The average age is 23 years, a birth peak age, although anti-NMDA-R
encephalitis is rare during pregnancy. The disorder is characterized by prominent
psychosis, dyskinesias, seizures, autonomic disturbance, and central
hypoventilation. We report a 24-year-old woman hospitalized at 28 gestational
weeks with acute-onset psychosis. Over the course of 3 weeks, her mental status
worsened until she fell into a coma. Both serum and cerebrospinal fluid anti-NMDA
R antibodies were found to be positive. At cesarean section, a healthy baby boy
was born and a wedge-shaped bilateral ovarian resection was performed. Treatment
with corticosteroids, intravenous immunoglobulin, and plasmapheresis can lead to
improved outcomes for both mother and baby.
PMID- 28418207
TI - Pyoderma gangrenosum in a pregnant patient: A case report and literature review.
AB - Pyoderma gangrenosum (PG) is a rare ulcerative skin disease that usually starts
as a pustular lesion and rapidly progresses to a painful ulcer with undermined
violaceous borders. The occurrence of PG during pregnancy is uncommon. We
describe a case of a pregnant patient with PG who was diagnosed as having
ulcerative colitis after delivery. Obstetricians need to understand the
pathogenesis of PG and its associated conditions because it is important to make
a proper diagnosis and provide targeted therapy.
PMID- 28418208
TI - Accuracy of self-collected human papillomavirus samples from Japanese women with
abnormal cervical cytology.
AB - AIM: The aim of this study was to assess the accuracy of self-collected vaginal
samples compared with physician-collected cervical samples for high-risk human
papillomavirus (HPV) testing in Japanese women with abnormal cervical cytology.
We also assessed the acceptability of self-collected HPV (sHPV) testing using a
questionnaire. METHODS: Women aged 20-69 years (n = 136) attending Yokohama City
University Hospital because of abnormal cervical cytology between April 2014 and
January 2015 were enrolled in this study. Cervical samples for conventional
cytology and physician-collected HPV (pHPV) testing were obtained before
colposcopic examination. After this examination, patients were asked to provide a
self-sampled vaginal specimen (sHPV) at home, some time between the following day
and the next week and to complete a self-sampling acceptability questionnaire.
RESULTS: The overall positive rates of HPV detection with pHPV and sHPV testing
were 61.0% (83/136) and 40.4% (55/136), respectively (P < 0.001). sHPV testing
had a lower sensitivity compared to pHPV for detection of cervical
intraepithelial neoplasia (CIN)2 or worse (CIN2+: 59.4% vs 100%, P < 0.001; CIN3:
66.7% vs 100%, P = 0.248). There were no statistically significant differences in
the sensitivity to detect CIN3 among pHPV testing, sHPV testing, and cytology.
The self-collecting device had good acceptability. CONCLUSION: sHPV testing is a
possible technique with which to improve poor cervical cancer screening uptake
rates in Japan; however, the sensitivity to detect CIN2+ lesions must improve
before it can be a substitute for conventional cytology or pHPV testing. Further
large-scale acceptability studies involving non-responders are also needed before
practical application.
PMID- 28418210
TI - Corrigendum.
PMID- 28418209
TI - Acupressure as adjuvant treatment for the inpatient management of nausea and
vomiting in early pregnancy: A double-blind randomized controlled trial.
AB - AIM: To evaluate the efficacy of acupressure at the Neiguan point (Pericardium
[P]6) as adjuvant treatment during inpatient management of severe nausea and
vomiting in pregnancy. METHODS: Low risk, spontaneously conceived singleton
pregnancies were randomly assigned to a treatment group, who received an
acupressure band placed at the Neiguan point (P6) or a placebo group who received
an otherwise identical non-stimulating wristband. Participants wore the band for
12 h daily for the first three days of admission. The primary outcome measure was
the severity of symptoms of nausea, vomiting and retching, recorded according to
Pregnancy-Unique Quantification of Emesis and Nausea score. RESULTS: There was a
statistically significant improvement in Pregnancy-Unique Quantification of
Emesis and Nausea scores from day 1 until day 3 of admission in the treatment
group compared with the placebo. Patients who received Neiguan point acupressure
also showed a significant improvement in their ketonuria scores. The treatment
group required a shorter hospital stay compared with the placebo. The only
reported side effect of the acupressure band was redness on the wrist.
CONCLUSIONS: The use of the acupressure band at the Neiguan point (P6) for 12 h
daily for three days for inpatients with hyperemesis gravidarum significantly
reduced the symptoms of nausea, vomiting and retching and ketonuria and led to a
reduction in hospital stay. We recommend the use of the acupressure band at the
Neiguan point (P6) as an adjunct/supplementary therapy to co-exist with the
standard care of management for hyperemesis gravidarum, particularly in low-risk
pregnant women.
PMID- 28418211
TI - Cutting costs and standardizing care: Once-per-cycle complete blood count
monitoring may be safe for patients undergoing platinum-based chemotherapy.
AB - AIM: The aim of this study was to evaluate whether frequency of complete blood
count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital
admissions or rates of neutropenic fever. METHODS: A retrospective cohort study
was performed at a single academic institution. Patients undergoing platinum
based chemotherapy for endometrial or ovarian cancer from January 2010 to
December 2014 were identified from a clinical database. Patients receiving dose
dense chemotherapy or on a clinical trial were excluded. Electronic chart review
collected demographic and clinical characteristics. The primary outcome was the
rate of febrile neutropenia or hospital admission. RESULTS: A total of 174
patients were identified, 63 (36%) with endometrial and 111 (64%) with ovarian
cancer. Fifty-four percent of patients received multiple CBC per cycle compared
with 46% who only had one CBC per cycle. The majority of patients were treated
with a platinum-based doublet (85%). Dose reductions, addition of granulocyte
colony stimulating factor, and rates of grade 3 or 4 anemia and neutropenia were
significantly associated with more frequent testing. There was no difference in
rates of neutropenic fever (5.3 vs 3.8%, P = 0.45) or hospital admission (22.3 vs
21.3%, P = 0.86) for multiple versus single CBC monitoring. CONCLUSION: More
frequent laboratory testing detected more cases of grade 3 or 4 hematopoietic
toxicities and was associated with more interventions. There were no differences
in number of hospitalizations or cases of neutropenic fever by frequency of
laboratory testing, suggesting that it may be appropriate to decrease routine
laboratory tests for select patients.
PMID- 28418212
TI - Role of autophagy in oocytogenesis, embryogenesis, implantation, and
pathophysiology of pre-eclampsia.
AB - Autophagy is a well-conserved mechanism in cells from yeast to mammals, and
autophagy maintains homeostasis against stress. The role of autophagy was
originally shown to be a mechanism of energy production under starvation. In
fact, multiple lines of evidence reveal that autophagy has numerous functions,
such as protection from stress, energy regulation, immune regulation,
differentiation, proliferation, and cell death. In the field of reproduction, the
role of autophagy in implantation, embryogenesis, placentation, and delivery has
become clearer. In addition, recent study has elucidated that the placenta has
the ability to protect extraplacental cells from virus infection by activating
autophagy. During resent research into autophagy, several issues have occurred in
the interpretation of the autophagy status. In this review, we discuss the
relation between autophagy and reproductive events, and show the importance of
autophagy for placentation and pre-eclampsia.
PMID- 28418213
TI - Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with
erythromelalgia, including the I848Tmutation in NaV 1.7.
AB - OBJECTIVES: Nociceptive thresholds and supra-threshold pain ratings as well as
their reduction upon local injection with lidocaine were compared between healthy
subjects and patients with erythromelalgia (EM). METHODS: Lidocaine (0.25, 0.50,
1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful
areas of the lower arm, in a randomized, double-blind manner, to test the effect
on dynamic and static mechanical sensitivity, mechanical pain sensitivity,
thermal thresholds and supra-threshold heat pain sensitivity. RESULTS: Heat pain
thresholds and pain ratings to supra-threshold heat stimulation did not differ
between EM-patients (n = 27) and controls (n = 25), neither did the dose-response
curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium
channel subunits NaV 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity
for supra-threshold heat stimuli, contrasting lower sensitivity to strong
mechanical stimuli. This pattern was particularly clear in the two patients
carrying the NaV 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on
mechanical pain sensitivity contrasted more effective heat analgesia. CONCLUSION:
Heat pain thresholds are not sensitized in EM patients, even in those with gain
of-function mutations in NaV 1.7. Differential lidocaine sensitivity was overt
only for noxious stimuli in the supra-threshold range suggesting that sensitized
supra-threshold encoding is important for the clinical pain phenotype in EM in
addition to lower activation threshold. Intracutaneous lidocaine dose-dependently
blocked nociceptive sensations, but we did not identify EM patients with
particular high lidocaine sensitivity that could have provided valuable
therapeutic guidance. SIGNIFICANCE: Acute pain thresholds and supra-threshold
heat pain in controls and patients with erythromelalgia do not differ and have
the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients
with the NaV 1.7 I848T mutation are normal and only nociceptor sensitivity to
intradermal lidocaine is changed. Only in EM patients with mutations in NaV 1.7,
1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine
sensitivity as compared to controls.
PMID- 28418214
TI - Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904
galactooligosaccharide use in humans.
AB - BACKGROUND: We have shown that a galactooligosaccharide prebiotic administration
(HOST-G904) initially increased intestinal gas production and this increase
declined back to baseline after 2 week administration. Our aim was to determine
the mechanism of microbiota adaptation; i.e., to determine whether the net
reduction is due to decreased overall production or increased gas consumption.
METHODS: In 10 healthy subjects, intestinal gas production and intraluminal
disposal was measured before, at the beginning and after 2 week of HOST-G904
prebiotic administration. Anal gas was collected for 4 hour after a probe meal.
Paired studies were performed without and with high-rate infusion of exogenous
gas (24 mL/min) into the jejunum to wash-out the endogenous gas produced by
bacterial fermentation. The exogenous gas infused was labeled (5% SF6 ) to
calculate the proportion of endogenous gas evacuated. KEY RESULTS: The volume of
intestinal gas produced i.e., endogenous gas washed-out, increased by 37% at the
beginning of HOST-G904 administration (P=.049 vs preadministration) and decreased
down to preadministration level after 2 week administration (P=.030 vs early
administration). The proportion of gas eliminated from the lumen before reaching
the anus tended to increase after 2-week administration (87+/-3% vs 78+/-5%
preadministration; P=.098). CONCLUSIONS & INFERENCES: Adaptation to regular
consumption of HOST-G904 prebiotic involves a shift in microbiota metabolism
toward low-gas producing pathways, with a non-significant increase in gas
consuming activity. Hence, regular consumption of HOST-G904 regulates intestinal
gas metabolism: less gas is produced and a somewhat larger proportion of it is
consumed.
PMID- 28418215
TI - Multichannel Porous TiO2 Hollow Nanofibers with Rich Oxygen Vacancies and High
Grain Boundary Density Enabling Superior Sodium Storage Performance.
AB - TiO2 as an anode for sodium-ion batteries (NIBs) has attracted much recent
attention, but poor cyclability and rate performance remain problematic owing to
the intrinsic electronic conductivity and the sluggish diffusivity of Na ions in
the TiO2 matrix. Herein, a simple process is demonstrated to improve the sodium
storage performance of TiO2 by fabricating a 1D, multichannel, porous binary
phase anatase-TiO2 -rutile-TiO2 composite with oxygen-deficient and high grain
boundary density (denoted as a-TiO2-x /r-TiO2-x ) via electrospinning and
subsequent vacuum treatment. The introduction of oxygen vacancies in the TiO2
matrix enables enhanced intrinsic electronic conductivity and fast sodium-ion
diffusion kinetics. The porous structure offers easy access of the liquid
electrolyte and a short transport path of Na+ through the pores toward the TiO2
nanoparticle. Furthermore, the high density of grain boundaries between the
anatase TiO2 and rutile TiO2 offer more interfaces for a novel interfacial
storage. The a-TiO2-x /r-TiO2-x shows excellent long cycling stability (134 mAh g
1 at 10 C after 4500 cycles) and superior rate performance (93 mAh g-1 after 4500
cycles at 20 C) for sodium-ion batteries. This simple and effective process could
serve as a model for the modification of other materials applied in energy
storage systems and other fields.
PMID- 28418216
TI - Adult attachment insecurity is positively associated with medically unexplained
chronic pain.
AB - BACKGROUND: Attachment insecurity (i.e. anxiety in relationships and/or
discomfort in close relationships) is associated with self-reports of physical
symptoms, medically unexplained symptoms and health conditions involving pain.
Medically unexplained chronic pain (MUCP) may represent a particularly severe
form of symptom reporting that is also characteristic of individuals with
insecure attachment. This study investigated relationships between adult
attachment style ratings and past-year MUCP in a sample of the general U.S.
population and the ability of attachment style ratings to account for variance in
past-year MUCP beyond that accounted for by potential confounders. METHOD: Data
from the National Comorbidity Survey Replication (N = 5645) were used. Attachment
was assessed with an interview-administered version of a commonly used self
report measure of secure, anxious and avoidant attachment. MUCP was assessed with
a brief interview. Depressive and anxiety disorders were included as covariates
and were assessed with a fully structured interview based on DSM-IV criteria.
RESULTS: The past-year prevalence of MUCP was 2.45% (95% CI = 2.07-2.83). The two
insecure attachment styles (i.e. anxious and avoidant) were positively associated
with MUCP. These associations remained statistically significant after adjusting
for demographic variables and depressive and anxiety disorders. When the two
insecure attachment styles were considered together, only avoidant attachment
remained significantly associated with MUCP. CONCLUSION: Attachment insecurity
ratings were positively associated with past-year MUCP and remained so after
statistically adjusting for depressive and anxiety disorders. Further research
aimed at understanding the mechanism(s) responsible for the association between
attachment insecurity and MUCP is warranted. SIGNIFICANCE: Consistent with
earlier research regarding transient physical symptoms, medically unexplained
chronic pain was associated with attachment insecurity. Understanding the
mechanisms responsible for this association could guide treatment innovations.
PMID- 28418217
TI - Twenty-four-hour variations in blood glucose level in Japanese type 2 diabetes
patients based on continuous glucose monitoring.
AB - AIMS/INTRODUCTION: High fluctuations in blood glucose are associated with various
complications. The correlation between glycated hemoglobin (HbA1c) level and
fluctuations in blood glucose level has not been studied in Japanese patients
with type 2 diabetes. In the present study, blood glucose profile stratified by
HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type
2 diabetes patients. MATERIALS AND METHODS: Our retrospective study included 294
patients with type 2 diabetes who were divided by HbA1c level into five groups
(>=6.0 to <7.0%, >=7.0 to <8.0%, >=8.0 to <9.0%, >=9.0 to <10.0% and >=10%). The
correlation between HbA1c level and CGM data was analyzed. The primary end-point
was the difference in blood glucose fluctuations among the HbA1c groups. RESULTS:
The mean blood glucose level increased significantly with increasing HbA1c
(Ptrend < 0.01). The standard deviation increased with increases in HbA1c
(Ptrend < 0.01). The mean amplitude of glycemic excursions did not vary
significantly with HbA1c. The levels of maximum blood glucose, minimum blood
glucose, each preprandial blood glucose, each postprandial maximum blood glucose,
range of increase in postprandial glucose from pre-meal to after breakfast, the
area under the blood concentration-time curve >180 mg/dL and percentage of the
area under the blood concentration-time curve >180 mg/dL were higher with higher
HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant
and independent determinants of HbA1c. CONCLUSIONS: In Japanese patients treated
for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate
with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c.
Parameters other than HbA1c are required to evaluate fluctuations in blood
glucose level in patients receiving treatment for type 2 diabetes.
PMID- 28418218
TI - Regulation of salt marsh mosquito populations by the 18.6-yr lunar-nodal cycle.
AB - The 18.6-yr lunar-nodal cycle drives changes in tidal amplitude globally,
affecting coastal habitat formation, species and communities inhabiting rocky
shores, and salt marsh vegetation. However, the cycle's influence on salt marsh
fauna lacked sufficient long-term data for testing its effect. We circumvented
this problem by using salt marsh mosquito records obtained over a period of over
four decades in two estuaries in the northeastern USA. Salt marsh mosquito
habitat is near the highest tide level where the impact of the nodal cycle on
flood frequency is greatest. Wavelet spectral and cross-correlation analyses
revealed periodicity in salt marsh mosquito abundance that was negatively
correlated with tidal amplitude. Tidal amplitude was a significant predictor of
salt marsh mosquito abundance with the cycle maxima coinciding with lower
mosquito populations, possibly due to access by predatory fish. However, these
effects were detected only at the location with extensive salt marsh habitat and
astronomical tides and were weakened or lacked significance at the location with
small microtidal salt marshes and wind-driven tides. Mosquitoes can serve as
proxy indicators for numerous invertebrate species on the salt marsh. These
predictable cycles and their effects need to be taken into consideration when
investigating, restoring, or managing intertidal communities that are also facing
sea-level rise.
PMID- 28418219
TI - Alpha-2 macroglobulin as a region-specific secretory protein in male reproductive
tract, and its dynamics during sperm transit toward the female spermatheca in the
blue crab.
AB - A 250-kDa protein was isolated from fluid in the middle spermatic duct (MSD) of
the blue crab (Portunus pelagicus). N-terminal and partial amino acid sequences
revealed that this MSD-specific protein is highly similar to the plasma-enriched
protein Alpha-2 macroglobulin (alpha2M). The P. pelagicus ortholog (Ppalpha2M) is
a large glycoprotein possessing mannose and N-acetylglucosamine residues. Ppa2m
mRNA was detected in the spermatic duct, androgenic gland, and hematopoietic
tissue, whereas the protein was primarily observed in the apical cytoplasm of MSD
epithelium and in the matrix of the acrosome of MSD sperm; distally within
spermatic duct, Ppalpha2M was lost from the sperm membrane but remained in the
sperm acrosome. These results suggest that Ppalpha2M is expressed and
glycosylated in the epithelium of spermatic ducts, secreted into MSD fluid, taken
up by sperm in the MSD, and removed from the surface of sperm during its transit
towards the female spermatheca. Given that Ppalpha2M also exhibits protease
inhibitor activity, we hypothesize that acrosome localized Ppalpha2M may suppress
premature acrosome reaction during post-testicular sperm maturation in this crab.
PMID- 28418220
TI - Diabetes technology.
PMID- 28418222
TI - Modified loop myopexy technique for severe high myopic strabismus fixus.
AB - IMPORTANCE: This study introduces a modified loop myopexy technique for severe
high myopic strabismus fixus. BACKGROUND: This study aims to evaluate the
surgical results of loop myopexy with or without medial rectus recession for the
treatment of patients with myopic strabismus fixus. DESIGN: This is a
retrospective study in a Chinese teaching hospital. PARTICIPANTS: Data was
collected from 25 myopic strabismus fixus patients (33 eyes) with restriction in
both abduction and sursumduction. METHODS: First, the loop myopexy technique was
performed. Following the loop myopexy technique, a medial rectus recession was
performed if esotropia remained. If esotropia and/or hypotropia still persisted,
second-stage surgery of the contralateral eye was performed. MAIN OUTCOME
MEASURES: The main outcome measures were ocular deviations, eye movements and the
angles of dislocation of the globe. RESULTS: At the last follow-up, mean
deviation of esotropia was significantly improved (10 vs. 92 PD; p = 0.000),
while mean deviation of hypotropia was improved (6 vs. 32 PD; p = 0.008). Mean
abduction limitation was improved (-2.7 vs. -5.0; p = 0.000); mean elevation
limitation improved (-3.2 vs. -5.0; p = 0.000). The angle of dislocation of the
globe was significantly decreased (103.0 vs. 235.3 D; p = 0.002). CONCLUSIONS AND
RELEVANCE: Modified Yokoyama's surgery effectively corrected the restrictive
esotropia and hypotropia, restored the dislocated globe back into the muscle cone
and improved the eye movement in severe myopic strabismus fixus.
PMID- 28418223
TI - Hydronium Ion Batteries: A Sustainable Energy Storage Solution.
AB - Hydronium ions have been reversibly stored for the first time in an electrode of
crystalline 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA). A highly
reversible discharge-charge behavior of PTCDA was observed in an aqueous acidic
electrolyte of 1 m H2 SO4 . The capacity and the operation potentials are
comparable to that of Na-ion storage in the same electrode.
PMID- 28418224
TI - A new drug nomenclature for psychiatry - prospects and hazards.
PMID- 28418225
TI - An Iterative Module in the Azalomycin F Polyketide Synthase Contains a Switchable
Enoylreductase Domain.
AB - Detailed analysis of the modular Type I polyketide synthase (PKS) involved in the
biosynthesis of the marginolactone azalomycin F in mangrove Streptomyces sp.
211726 has shown that only nineteen extension modules are required to accomplish
twenty cycles of polyketide chain elongation. Analysis of the products of a PKS
mutant specifically inactivated in the dehydratase domain of extension-module 1
showed that this module catalyzes two successive elongations with different
outcomes. Strikingly, the enoylreductase domain of this module can apparently be
"toggled" off and on : it functions in only the second of these two cycles. This
novel mechanism expands our understanding of PKS assembly-line catalysis and may
explain examples of apparent non-colinearity in other modular PKS systems.
PMID- 28418227
TI - Barriers and facilitators to implementing family support and education in Early
Psychosis Intervention programmes: A systematic review.
AB - Family support is a core component of the Early Psychosis Intervention (EPI)
model, yet it continues to have relatively low rates of implementation in
practice. This paper reports results of a literature review on facilitators and
barriers to delivering family interventions in EPI programmes. A search was
conducted of 4 electronic databases, Medline, EMBASE, PsycINFO and Joanna Briggs,
from 2000 to 2015 using terms related to early onset psychosis, family work and
implementation. Four thousand four hundred and two unique studies were
identified, 7 of which met inclusion criteria. Barriers and facilitators were
coded and aggregated to higher-level themes using a consensus approach. Five of 7
studies examined structured multifamily psychoeducation. Uptake by families was
affected by: family/client interest and readiness to participate; ability to
access supports; and support needs/preferences. Implementation by programmes was
affected by staff access to training and resources to provide family support. A
key finding across the identified studies was that families have different needs
and preferences regarding the timing, length, intensity and content of the
intervention. One size does not fit all and many families do not require the
intensive psychoeducational programmes typically provided. The reviewed
literature suggests that flexible, tiered approaches to care may better meet
family needs and increase rates of uptake of family support. However, more
research is needed on the effectiveness of different models of family support in
early psychosis and how they can be successfully implemented.
PMID- 28418226
TI - Serum monomeric laminin-gamma2 as a novel biomarker for hepatocellular carcinoma.
AB - The diagnosis of hepatocellular carcinoma (HCC) in the early stages is important
for successful clinical management. Laminin (Ln)-gamma2 expression has been
reported in various types of malignant carcinomas. We recently developed a highly
sensitive method to measure serum monomeric Ln-gamma2 levels using a fully
automated chemiluminescent immunoassay (CLIA). Using our CLIA, we evaluated its
diagnostic value in sera from patients with chronic liver disease (CLD) and
patients with hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) and
des-gamma-carboxy prothrombin (DCP) were also examined in these subjects. Median
levels of Ln-gamma2 were significantly higher in patients with HCC (173.2 pg/mL;
range: 39.5-986 pg/mL) compared with patients with CLD (76.7 pg/mL; range: 38.7
215.9 pg/mL) and with healthy volunteers (41.1 pg/mL; range: 10.9-79.0 pg/mL).
The optimal cutoff value for Ln-gamma2 that allowed us to distinguish between HCC
and nonmalignant CLD was 116.6 pg/mL. Elevated Ln-gamma2 levels were observed in
0% of healthy volunteers, 17% of patients with CLD, and 63% of patients with HCC.
The positivity rate in patients with HCC for the combination of Ln-gamma2 and DCP
was 89.5%, which was better than that for either of the two markers alone (63%
and 68%, respectively). Among patients with early-stage HCC (T1 or T2), the
positivity rates for monomeric Ln-gamma2, AFP and DCP were 61%, 39% and 57%,
respectively. Serum Ln-gamma2 may be a potential biomarker for HCC surveillance.
The combination of Ln-gamma2 and DCP may be more sensitive for laboratory
diagnosis of HCC than the combination of AFP and DCP.
PMID- 28418228
TI - Probiotics-impregnated bedding covers for house dust mite allergic rhinitis: A
pilot randomized clinical trial.
PMID- 28418230
TI - Corrigendum for Blonder et al. (2017) DOI: 10.1111/ele.12736.
PMID- 28418229
TI - Assembly of a Benzo-Fused Bridged Ketone Scaffold from 1,5,10-Enediynes through
One-Pot Ruthenium-Catalyzed Cyclization/Iodine-Mediated Oxidative Ring Expansion.
AB - In the presence of a cationic Ru catalyst, 1,6-diynes bearing a terminal styryl
moiety underwent [2+2+2] cyclization to produce dehydrobiphenylenes fused with a
five-membered ring. Although the cycloadducts were unstable toward purification,
their one-pot iodine-mediated ring expansion successfully afforded unprecedented
bridged ketone products containing a benzo-fused bicyclo[3.2.1] framework.
PMID- 28418231
TI - A Dendritic Amphiphile for Efficient Control of Biomimetic Calcium Phosphate
Mineralization.
AB - The phase behavior of a dendritic amphiphile containing a Newkome-type dendron as
the hydrophilic moiety and a cholesterol unit as the hydrophobic segment is
investigated at the air-liquid interface. The amphiphile forms stable
monomolecular films at the air-liquid interface on different subphases.
Furthermore, the mineralization of calcium phosphate beneath the monolayer at
different calcium and phosphate concentrations versus mineralization time shows
that at low calcium and phosphate concentrations needles form, whereas flakes and
spheres dominate at higher concentrations. Energy-dispersive X-ray spectroscopy,
X-ray photoelectron spectroscopy, and electron diffraction confirm the formation
of calcium phosphate. High-resolution transmission electron microscopy and
electron diffraction confirm the predominant formation of octacalcium phosphate
and hydroxyapatite. The data also indicate that the final products form via a
complex multistep reaction, including an association step, where nano-needles
aggregate into larger flake-like objects.
PMID- 28418233
TI - In Situ Expanding Pores of Dodecahedron-like Carbon Frameworks Derived from MOFs
for Enhanced Capacitive Deionization.
AB - The pores of dodecahedron-like carbon frameworks derived from metal-organic
frameworks (MOFs) were in situ expanded via a surfactant-template strategy, which
were originally demonstrated to enhance capacitive deionization (CDI). The
dodecahedron-like carbon frameworks were obtained through carbonization of
zeolitic imidazolate framework-8 (ZIF-8) using the cetyltrimethylammonium bromide
as a supramolecular template. It is found that the dodecahedron-like carbon
frameworks derived from ZIF-8 possess efficiently expanded pores while retaining
the original morphology and high nitrogen contents. Compared to those of the
normal ZIF-8-derived carbon, the obtained materials exhibit a hierarchically
porous structure with a higher specific surface area and an improved pore volume.
Electrochemical studies of the obtained electrode demonstrate that this material
has a high specific capacitance and lower inner resistance. More importantly, the
obtained material shows a higher salt adsorption capacity (20.05 mg/g) than the
normal ZIF-8-derived carbon (13.01 mg/g). Furthermore, the obtained electrode
presents a rapid salt removal rate and excellent cycling stability. The
significantly enhanced deionization behavior of the obtained materials is due to
the combination effect of its large accessible surface area, large pore volume,
and rich nitrogen doping. The results reveal that in situ expanding pores of
carbon frameworks derived from MOFs is an ideal way for constructing electrode
materials with enhanced CDI performance. The present work may pave a path for the
design and development of highly efficient MOF-derived electrode materials.
PMID- 28418232
TI - High pre-exposure prophylaxis uptake and early adherence among men who have sex
with men and transgender women at risk for HIV Infection: the PrEP Brasil
demonstration project.
AB - INTRODUCTION: The efficacy of pre-exposure prophylaxis (PrEP) in preventing
sexual acquisition of human immunodeficiency virus (HIV) is well established.
Little is known about the feasibility of PrEP implementation in middle-income
settings with concentrated epidemics among men who have sex with men (MSM) and
transgender women (TGW). METHODS: PrEP Brasil is a prospective, multicentre, open
label demonstration project assessing PrEP delivery in the context of the
Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres
in Rio de Janeiro and Sao Paulo were evaluated for eligibility and offered 48
weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir
diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early
adherence) were measured. Predictors of drug levels were assessed using ordinal
logistic regression models considering the DBS drug level as a 3 level variable
(<350 fmol/punch, >=350-699 fmol/punch and >=700 fmol/punch). RESULTS: 1,270
individuals were assessed for participation; n = 738 were potentially eligible
and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled
individuals were younger, had lower HIV risk perception and had lower PrEP
awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP
concentrations, 94.1% in the protective range (>=350 fmol/punch, consistent with
>=2 pills per week), and 78% were in the highly protective range (>=700
fmol/punch, >=4 pills per week). Participants with >=12 years of schooling had
1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than
participants with <12 years of schooling. Condomless receptive anal intercourse
in the prior 3 months was also associated with higher drug levels (adjusted OR =
1.78; 95% CI 1.08-2.94). CONCLUSION: The high uptake and early adherence indicate
that PrEP for high-risk MSM and TGW can be successfully delivered in the context
of the Brazilian Public Health System. Interventions to address disparities on
PrEP awareness and HIV risk perception among the younger and less educated are
urgently needed in order to maximize the impact of this prevention strategy on
the reduction of HIV infection among MSM and TGW in Brazil.
PMID- 28418234
TI - Piezoresistive Effect in Plasma-Doping of Graphene Sheet for High-Performance
Flexible Pressure Sensing Application.
AB - This paper presents a straightforward plasma treatment modification of graphene
with an enhanced piezoresistive effect for the realization of a high-performance
pressure sensor. The changes in the graphene in terms of its morphology,
structure, chemical composition, and electrical properties after the NH3/Ar
plasma treatment were investigated in detail. Through a sufficient plasma
treatment condition, our studies demonstrated that plasma-treated graphene sheet
exhibits a significant increase in sensitivity by one order of magnitude compared
to that of the unmodified graphene sheet. The plasma-doping introduced nitrogen
(N) atoms inside the graphene structure and was found to play a significant role
in enhancing the pressure sensing performance due to the tunneling behavior from
the localized defects. The high sensitivity and good robustness demonstrated by
the plasma-treated graphene sensor suggest a promising route for simple, low
cost, and ultrahigh resolution flexible sensors.
PMID- 28418235
TI - Discovery of the Showdomycin Gene Cluster from Streptomyces showdoensis ATCC
15227 Yields Insight into the Biosynthetic Logic of C-Nucleoside Antibiotics.
AB - Nucleoside antibiotics are a large class of pharmaceutically relevant chemical
entities, which exhibit a broad spectrum of biological activities. Most
nucleosides belong to the canonical N-nucleoside family, where the heterocyclic
unit is connected to the carbohydrate through a carbon-nitrogen bond. However,
atypical C-nucleosides were isolated from Streptomyces bacteria over 50 years
ago, but the molecular basis for formation of these metabolites has been unknown.
Here, we have sequenced the genome of S. showdoensis ATCC 15227 and identified
the gene cluster responsible for showdomycin production. Key to the detection was
the presence of sdmA, encoding an enzyme of the pseudouridine monophosphate
glycosidase family, which could catalyze formation of the C-glycosidic bond.
Sequence analysis revealed an unusual combination of biosynthetic genes, while
inactivation and subsequent complementation of sdmA confirmed the involvement of
the locus in showdomycin formation. The study provides the first steps toward
generation of novel C-nucleosides by pathway engineering.
PMID- 28418236
TI - Novel Approach of Using Near-Infrared Responsive PEGylated Gold Nanorod Coated
Poly(l-lactide) Microneedles to Enhance the Antitumor Efficiency of Docetaxel
Loaded MPEG-PDLLA Micelles for Treating an A431 Tumor.
AB - The combination of chemotherapy and photothermal therapy (PTT) plays a
significant role in synergistic tumor therapy. However, a high dosage of
chemotherapy drugs or photothermal agents may cause series side effects. To
overcome these challenges, we designed a near-infrared (NIR) responsive PEGylated
gold nanorod (GNR-PEG) coated poly(l-lactide) microneedle (PLLA MN) system (GNR
PEG@MN) to enhance antitumor efficiency of docetaxel-loaded MPEG-PDLLA (MPEG
PDLLA-DTX) micelles for treating an A431 tumor. The as-made GNR-PEG@MNs contained
only 31.83 +/- 1.22 MUg of GNR-PEG per patch and exhibited excellent heating
efficacy both in vitro and in vivo. Meanwhile, GNR-PEG@MN with the height of 480
MUm had good skin insertion ability and was harmless to the skin. On the other
hand, GNR-PEG@MN had good heating transfer ability in vivo, and the tumor sites
could reach 50 degrees C within 5 min. In comparison with chemotherapy and PTT
alone, the combination of low dosage MPEG-PDLLA-DTX micelles (5 mg/kg) and GNR
PEG@MNs completely eradicated the A431 tumor without recurrence in vivo,
demonstrating a remarkable synergetic effect. Hence, GNR-PEG@MN could be a
promising carrier to enhance the antitumor effect of MPEG-PDLLA-DTX micelles for
treating superficial tumors and is expected to have a great potential in clinical
translation for human epidermoid cancer therapy.
PMID- 28418238
TI - Specific and Differential Binding of N-Acetylgalactosamine Glycopolymers to the
Human Macrophage Galactose Lectin and Asialoglycoprotein Receptor.
AB - A range of glycopolymers composed of N-acetylgalactosamine were prepared via
sequential Cu(I)-mediated polymerization and alkyne-azide click (CuAAC). The
resulting polymers were shown, via multichannel surface plasmon resonance, to
interact specifically with human macrophage galactose lectin (MGL; CD301) with
high affinity (KD = 1.11 MUM), but they did not bind to the mannose/fucose
selective human lectin dendritic-cell-specific intercellular adhesion molecule-3
grabbing nonintegrin (DC-SIGN; CD209). The effect of sugar ligand valency on the
binding (so-called "glycoside cluster effect") of poly(N-acetylgalactosamine) to
MGL was investigated by varying first the polymer chain length (DP: 100, 64, 40,
23, 12) and then the architecture (4- and 8-arm star glycopolymers). The chain
length did not have a significant effect on the binding to MGL (KD = 0.17-0.52
MUM); however, when compared to a hepatic C-type lectin of a similar
monosaccharide specificity, the asialoglycoprotein receptor (ASGPR), the binding
affinity was more noticeably affected (KD = 0.37- 6.65 MUM). These data suggest
that known differences in the specific configuration/orientation of the
carbohydrate recognition domains of MGL and ASGPR are responsible for the
differences in binding observed between the different polymers of varied chain
length and architecture. In the future, this model has the potential to be
employed for the development of tissue-selective delivery systems.
PMID- 28418237
TI - What Gene Mutations Affect Serotonin in Mice?
AB - Although serotonin neurotransmission has been implicated in several
neurodevelopmental and psychological disorders, the factors that drive
dysfunction of the serotonin system are poorly understood. Current research
regarding the serotonin system revolves around its dysfunction in
neuropsychiatric disorders, but there is no database collating genetic mutations
that result in serotonin abnormalities. To bridge this gap, we developed a list
of genes in mice that, when perturbed, result in altered levels of serotonin
either in brain or blood. Due to the intrinsic limitations of search, the current
list should be considered a preliminary subset of all relevant cases.
Nevertheless, it offered an opportunity to gain insight into what types of genes
have the potential to impact serotonin by using gene ontology (GO). This analysis
found that genes associated with monoamine metabolism were more often associated
with increases in brain serotonin than decreases. Speculatively, this could be
because several pathways (and therefore many genes) are responsible for the
clearance and metabolism of serotonin whereas only one pathway (and therefore
fewer genes) is directly involved in the synthesis of serotonin. Another
contributor could be cross talk between monoamine systems such as dopamine. In
contrast, genes that were associated with decreases in brain serotonin were more
likely linked to a developmental process. Sensitivity of serotonin neurons to
developmental perturbations could be due to their complicated neuroanatomy or
possibly they may be negatively regulated by dysfunction of their innervation
targets. Thus, these observations suggest hypotheses regarding the mechanisms
underlying the vulnerability of brain serotonin neurotransmission.
PMID- 28418239
TI - Oxygen Vacancy Associated Surface Fenton Chemistry: Surface Structure Dependent
Hydroxyl Radicals Generation and Substrate Dependent Reactivity.
AB - Understanding the chemistry of hydrogen peroxide (H2O2) decomposition and
hydroxyl radical (*OH) transformation on the surface molecular level is a great
challenge for the application of heterogeneous Fenton system in the fields of
chemistry, environmental, and life science. We report in this study a conceptual
oxygen vacancy associated surface Fenton system without any metal ions leaching,
exhibiting unprecedented surface chemistry based on the oxygen vacancy of
electron-donor nature for heterolytic H2O2 dissociation. By controlling the
delicate surface structure of catalyst, this novel Fenton system allows the
facile tuning of *OH existing form for targeted catalytic reactions with
controlled reactivity and selectivity. On the model catalyst of BiOCl, the
generated *OH tend to diffuse away from the (001) surface for the selective
oxidation of dissolved pollutants in solution, but prefer to stay on the (010)
surface, reacting with strongly adsorbed pollutants with high priority. These
findings will extend the scope of Fenton catalysts via surface engineering and
consolidate the fundamental theories of Fenton reactions for wide environmental
applications.
PMID- 28418240
TI - Enzymatic Carbon-Sulfur Bond Formation in Natural Product Biosynthesis.
AB - Sulfur plays a critical role for the development and maintenance of life on
earth, which is reflected by the wealth of primary metabolites, macromolecules,
and cofactors bearing this element. Whereas a large body of knowledge has existed
for sulfur trafficking in primary metabolism, the secondary metabolism involving
sulfur has long been neglected. Yet, diverse sulfur functionalities have a major
impact on the biological activities of natural products. Recent research at the
genetic, biochemical, and chemical levels has unearthed a broad range of enzymes,
sulfur shuttles, and chemical mechanisms for generating carbon-sulfur bonds. This
Review will give the first systematic overview on enzymes catalyzing the
formation of organosulfur natural products.
PMID- 28418241
TI - Unique Ruthenium Bimetallic Supramolecular Cages From C4-Symmetric Tetrapyridyl
Metalloligands.
AB - The self-assembly of C4-symmetric tetrapyridyl metalloligands containing Fe or Co
and diruthenium electron acceptors by means of dative coordination bonding led to
the formation of six different heterobimetallic supramolecules. All complexes
were characterized by X-ray crystallography, ESI mass spectrometry, and 1H NMR
(in the case of diamagnetic systems) spectroscopy. The bridging units in the
diruthenium complexes greatly influenced the geometrical preference of the
supramolecular structures, resulting in the formation of different architectures,
namely A4D2 or A6D3 (A = acceptor, D = donor). Depending on the bridging unit,
A4D2 tetragonal prism, A4D2 molecular tweezer, or A6D3 triple-decker complexes
were obtained selectively. The self-assembly of an unexpected triple-decker type
Ru12Fe3 heterobimetallic species was also observed.
PMID- 28418243
TI - General Approach toward Aspidospermatan-Type Alkaloids Using One-Pot Vilsmeier
Haack Cyclization and Azomethine Ylide Cycloaddition.
AB - The development of a new one-pot reaction sequence afforded the tricyclic core of
several aspidospermatan-type alkaloids from a linear, densely functionalized
substrate. The key sequence features a highly chemoselective formamide activation
that triggered a Vilsmeier-Haack cyclization, followed by an azomethine ylide
generation and intramolecular cycloaddition. The choice of nucleophile,
azomethine ylide precursor, and dipolarophile was crucial to the success of the
sequence.
PMID- 28418244
TI - Applying Bayesian Approach to Combinatorial Problem in Chemistry.
AB - A Bayesian optimization procedure, in combination with density functional theory
calculations, was applied to a combinatorial problem in chemistry. As a specific
example, we examined the stable structures of lithium-graphite intercalation
compounds (Li-GICs). We found that this approach efficiently identified the
stable structure of stage-I and -II Li-GICs by calculating 4-6% of the full
search space. We expect that this approach will be helpful in solving problems in
chemistry that can be regarded as a kind of combinatorial problem.
PMID- 28418242
TI - Slow but Steady Wins the Race: Dissimilarities among New Dual Inhibitors of the
Wild-Type and the V27A Mutant M2 Channels of Influenza A Virus.
AB - New insights on the amantadine resistance mechanism of the V27A mutant were
obtained through the study of novel, easily accessible 4-(1- and 2
adamantyl)piperidines, identified as dual binders of the wild-type and V27A
mutant M2 channels of influenza A virus. Their antiviral activity and channel
blocking ability were determined using cell-based assays and two-electrode
voltage clamp (TEVC) technique on M2 channels, respectively. In addition,
electrophysiology experiments revealed two interesting findings: (i) these
inhibitors display a different behavior against the wild-type versus V27A mutant
A/M2 channels, and (ii) the compounds display antiviral activity when they have
kd equal or smaller than 10-6 while they do not exhibit antiviral activity when
kd is 10-5 or higher although they may show blocking activity in the TEV assay.
Thus, caution must be taken when predicting antiviral activity based on percent
channel blockage in electrophysiological assays. These findings provide
experimental evidence of the resistance mechanism of the V27A mutation to wild
type inhibitors, previously predicted in silico, offer an explanation for the
lack of antiviral activity of compounds active in the TEV assay, and may help
design new and more effective drugs.
PMID- 28418245
TI - Geranylpyrrol A and Piericidin F from Streptomyces sp. CHQ-64 DeltardmF.
AB - Two new compounds, geranylpyrrol A (1) and piericidin F (2), were isolated from a
reedsmycins nonproducing mutant strain of Streptomyces sp. CHQ-64. Their
structures, including absolute configurations, were elucidated by extensive NMR,
MS, NOESY, and ECD analyses. Geranylpyrrol A (1) is an unusual naturally
occurring 2,3,4-trisubstituted pyrrole, and piericidin F (2) showed cytotoxicity
against HeLa, NB4, A549, and H1975 cell lines with IC50 values of 0.003, 0.037,
0.56, and 0.49 MUM, respectively.
PMID- 28418246
TI - Water-Ice Analogues of Polycyclic Aromatic Hydrocarbons: Water Nanoclusters on
Cu(111).
AB - Water has an incredible ability to form a rich variety of structures, with 16
bulk ice phases identified, for example, as well as numerous distinct structures
for water at interfaces or under confinement. Many of these structures are built
from hexagonal motifs of water molecules, and indeed, for water on metal
surfaces, individual hexamers of just six water molecules have been observed.
Here, we report the results of low-temperature scanning tunneling microscopy
experiments and density functional theory calculations which reveal a host of new
structures for water-ice nanoclusters when adsorbed on an atomically flat Cu
surface. The H-bonding networks within the nanoclusters resemble the resonance
structures of polycyclic aromatic hydrocarbons, and water-ice analogues of inene,
naphthalene, phenalene, anthracene, phenanthrene, and triphenylene have been
observed. The specific structures identified and the H-bonding patterns within
them reveal new insight about water on metals that allows us to refine the so
called "2D ice rules", which have so far proved useful in understanding water-ice
structures at solid surfaces.
PMID- 28418247
TI - High and Stable Ionic Conductivity in 2D Nanofluidic Ion Channels between Boron
Nitride Layers.
AB - Achieving a high rate of ionic transport through porous membranes and ionic
channels is important in numerous applications ranging from energy storage to
water desalination, but it still remains a challenge. Herein we show that ions
can quickly pass through interlayer spaces in hydrated boron nitride (BN)
membranes. Measurements of surface-charge governed ionic currents between BN
nanosheets in a variety of salt solutions (KCl, NaCl and CaCl2) at low salt
concentrations (<10-4 M) showed several orders of magnitude higher ionic
conductivity compared to that of the bulk solution. Moreover, due to the
outstanding chemical and thermal stability of BN, the ionic conduits remain fully
functional at temperatures up to 90 degrees C. The BN conduits can operate in
acidic and basic environments and do not degrade after immersing in solutions
with extreme pH (pH ~ 0 or 14) for 1 week. Those excellent properties make the BN
ionic conduits attractive for applications in nanofluidic devices and membrane
separation.
PMID- 28418248
TI - Total Synthesis, Configuration Assignment, and Cytotoxic Activity Evaluation of
Protulactone A.
AB - The first total synthesis and absolute configuration assignment of protulactone A
(1) has been achieved. Four stereoisomers, 1a, ent-1a, 1b, and ent-1b, of this
natural polyketide were prepared by chiral pool synthesis starting from l- and d
arabinose, respectively. The absolute and relative configurations of all isomers
were assigned by single-crystal X-ray analysis. Target compounds were screened
for their in vitro cytotoxicity toward certain human tumor cells (NCI60 cancer
cell line panel).
PMID- 28418249
TI - beta-Hydride Elimination and C-H Activation by an Iridium Acetate Complex,
Catalyzed by Lewis Acids. Alkane Dehydrogenation Cocatalyzed by Lewis Acids and
[2,6-Bis(4,4-dimethyloxazolinyl)-3,5-dimethylphenyl]iridium.
AB - NaBArF4 (sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate) was found to
catalyze reactions of (Phebox)IrIII(acetate) (Phebox = 2,6-bis(4,4
dimethyloxazolinyl)-3,5-dimethylphenyl) complexes, including (i) beta-H
elimination of (Phebox)Ir(OAc)(n-alkyl) to give (Phebox)Ir(OAc)(H) and the
microscopic reverse, alkene insertion into the Ir-H bond of (Phebox)Ir(OAc)(H),
and (ii) hydrogenolysis of the Ir-alkyl bond of (Phebox)Ir(OAc)(n-alkyl) and the
microscopic reverse, C-H activation by (Phebox)Ir(OAc)(H), as indicated by H/D
exchange experiments. For example, beta-H elimination of (Phebox)Ir(OAc)(n-octyl)
(2-Oc) proceeded on a time scale of minutes at -15 degrees C in the presence of
(0.4 mM) NaBArF4 as compared with a very slow reaction at 125 degrees C in the
absence of NaBArF4. In addition to NaBArF4, other Lewis acids are also effective.
Density functional theory calculations capture the effect of the Na+ cation and
indicate that it operates primarily by promoting kappa2-kappa1 dechelation of the
acetate anion, which opens the coordination site needed to allow the observed
reaction to proceed. In accord with the effect on these individual stoichiometric
reactions, NaBArF4 was also found to cocatalyze, with (Phebox)Ir(OAc)(H), the
acceptorless dehydrogenation of n-dodecane.
PMID- 28418250
TI - Identifying the Active Surfaces of Electrochemically Tuned LiCoO2 for Oxygen
Evolution Reaction.
AB - Identification of active sites for catalytic processes has both fundamental and
technological implications for rational design of future catalysts. Herein, we
study the active surfaces of layered lithium cobalt oxide (LCO) for the oxygen
evolution reaction (OER) using the enhancement effect of electrochemical
delithiation (De-LCO). Our theoretical results indicate that the most stable
(0001) surface has a very large overpotential for OER independent of lithium
content. In contrast, edge sites such as the nonpolar (1120) and polar (0112)
surfaces are predicted to be highly active and dependent on (de)lithiation. The
effect of lithium extraction from LCO on the surfaces and their OER activities
can be understood by the increase of Co4+ sites relative to Co3+ and by the shift
of active oxygen 2p states. Experimentally, it is demonstrated that LCO
nanosheets, which dominantly expose the (0001) surface show negligible OER
enhancement upon delithiation. However, a noticeable increase in OER activity
(~0.1 V in overpotential shift at 10 mA cm-2) is observed for the LCO
nanoparticles, where the basal plane is greatly diminished to expose the edge
sites, consistent with the theoretical simulations. Additionally, we find that
the OER activity of De-LCO nanosheets can be improved if we adopt an acid etching
method on LCO to create more active edge sites, which in turn provides a strong
evidence for the theoretical indication.
PMID- 28418251
TI - Enantio- and Diastereoselective Nitro-Mannich Reaction of alpha-Aryl
Nitromethanes with Amidosulfones Catalyzed by Phase-Transfer Catalysts.
AB - A high-yield, highly diastereo- and enantioselective nitro-Mannich reaction of
alpha-aryl nitromethanes with amidosulfones catalyzed by a novel chiral phase
transfer catalyst, bearing multiple H-bonding donors, derived from quinine was
developed. A variety of alpha-aryl nitromethanes and amidosulfones were
investigated; and the corresponding products were obtained in excellent yields
with excellent diastereo- and enantioselectivities (up to 99% yield, > 99:1 dr
and >99% ee). As a demonstration of synthetic utility, the resulting beta
nitroamines could be converted to corresponding meso-symmetric and optically pure
unsymmetric anti-1,2-diarylethylenediamines.
PMID- 28418252
TI - Electronic and Structural Study of ZnxSx [x = 12, 16, 24, 28, 36, 48, 96, and
108] Cage Structures.
AB - We present a density functional study on the structural and electronic properties
of ZnS bubble clusters, specifically, hollow cages whose spontaneous formation
was previously observed in classical molecular dynamics simulations by Spano et
al. [J. Phys. Chem. B 2003, 107, 10337]. The hollow ZnS cages in our study were
modeled as ZnxSx [x = 12, 16, 24, 28, 36, 48, 108], and an onionlike structure
was modeled as Zn96S96. The study of energetics and stability, performed using
large polarized Gaussian basis sets, indicated all structures to be energetically
stable with similar binding energy of 5.5-5.6 eV per ZnS pair. Further
computation of electronic properties showed that these cages have large vertical
ionization energies and relatively low electron affinities in the ranges of 6.8
8.1 and 1.7-3.0 eV, respectively. They have large highest occupied molecular
orbital-lowest unoccupied molecular orbital gaps between 2.5 and 3.3 eV, and
quasi-particle gaps vary from 6.2 eV for Zn12S12 to 4.19 for Zn108S108. The
computed vibrational frequencies for selected cages, that is, Zn12S12, Zn16S16,
Zn28S28 (O, S4, and S8 point groups), and Zn36S36 indicate that these cage
structures correspond to local minima on the potential energy surface. Finally,
the infrared spectra calculated using large basis sets are also reported.
PMID- 28418253
TI - Species-Level Discrimination of Psychrotrophic Pathogenic and Spoilage Gram
Negative Raw Milk Isolates Using a Combined MALDI-TOF MS Proteomics
Bioinformatics-based Approach.
AB - Identification of psychrotrophic pathogenic and spoilage Gram-negative bacteria
using rapid and reliable techniques is important in commercial milk processing,
as these bacteria can produce heat-resistant proteases and act as postprocessing
contaminants in pasteurized milk. Matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry (MALDI-TOF MS) is a proven technology for
identification of bacteria in food, however, may require optimization for
identification of pathogenic and spoilage bacteria in milk and dairy products.
The current study evaluated the effects of various culture conditions and sample
preparation methods on assigning of raw milk isolates to the species level by
MALDI-TOF MS. The results indicated that culture media, incubation conditions
(temperature and time), and sample preparation significantly affected the
identification rates of bacteria to the species level. Nevertheless, the
development of spectral libraries of isolates grown on different media using a
web tool for hierarchical clustering of peptide mass spectra (SPECLUST) followed
by a ribosomal protein based bioinformatics approach significantly enhanced the
assigning of bacteria, with at least one unique candidate biomarker peak
identified for each species. Phyloproteomic relationships based on spectral
profiles were compared to phylogenetic analysis using 16S rRNA gene sequences and
demonstrated similar clustering patterns with significant discriminatory power.
Thus, with appropriate optimization, MALDI-TOF MS is a valuable tool for species
level discrimination of pathogenic and milk spoilage bacteria.
PMID- 28418254
TI - Evaluating the Characteristics of Reporter Ion Signal Acquired in the Orbitrap
Analyzer for Isobaric Mass Tag Proteome Quantification Experiments.
AB - Multiplexed quantification with isobaric chemical tags (e.g., TMT, iTRAQ)
provides a robust and efficient means to comparatively examine proteome dynamics
between several biological states using a mass spectrometer (MS). The
quantitative nature of isobaric tags necessitates strict validation of the
observed ion signals in the chosen MS detector before differential patterns are
extracted between biological states. We present an in-depth analysis of isobaric
tag data acquired on current generation Orbitrap MS hardware to illustrate
pitfalls in acquisition settings that can negatively impact results. We
establish, for the first time, the presence of a notch, a region of no observed
values, in the reporter ion distributions from isobaric-labeled peptide mixtures
acquired on these instruments. We determine that this notch is present in
published data across a wide range of instruments of the same or different type
and is isolated to the Orbitrap mass analyzer. We demonstrate that the impact of
the notch can be minimized using manipulations of Orbitrap scan parameters and on
column injection amounts. Lastly, using a mixture of synthetic standard peptides
we investigated the impact on identification rates and quantification precision.
Together, these data highlight an important phenomenon that negatively impacts
peptide identification and quantification in the Orbitrap analyzer as well as
outlining guidelines to follow to ensure minimization of MS-induced artifacts in
isobaric tag experiments resulting from the notch.
PMID- 28418255
TI - Transient Clustering of Reaction Intermediates during Wet Etching of Silicon
Nanostructures.
AB - Wet chemical etching is a key process in fabricating silicon (Si) nanostructures.
Currently, wet etching of Si is proposed to occur through the reaction of surface
Si atoms with etchant molecules, forming etch intermediates that dissolve
directly into the bulk etchant solution. Here, using in situ transmission
electron microscopy (TEM), we follow the nanoscale wet etch dynamics of amorphous
Si (a-Si) nanopillars in real-time and show that intermediates generated during
alkaline wet etching first aggregate as nanoclusters on the Si surface and then
detach from the surface before dissolving in the etchant solution. Molecular
dynamics simulations reveal that the molecules of etch intermediates remain
weakly bound to the hydroxylated Si surface during the etching and aggregate into
nanoclusters via surface diffusion instead of directly diffusing into the etchant
solution. We confirmed this model experimentally by suppressing the formation of
nanoclusters of etch intermediates on the Si surfaces by shielding the
hydroxylated Si sites with large ions. These results suggest that the interaction
of etch intermediates with etching surfaces controls the solubility of reaction
intermediates and is an important parameter in fabricating densely packed clean
3D nanostructures for future generation microelectronics.
PMID- 28418256
TI - Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four
Stereoisomers of Sphinganine.
AB - All four stereoisomers of sphinganine can be synthesized by a multicomponent
aziridination of an aldehyde, an amine and an alpha-diazo carbonyl compound
mediated by a BOROX catalyst with high asymmetric induction (>=96% ee). The threo
isomers are available from ring-opening of cis-aziridines by an oxygen
nucleophile with inversion at the C-3 position and the erythro-isomers are
likewise available from trans-aziridines.
PMID- 28418257
TI - Investigating Acquisition Performance on the Orbitrap Fusion When Using Tandem
MS/MS/MS Scanning with Isobaric Tags.
AB - Methods for isobaric-tagged peptide analysis (e.g., TMT, iTRAQ), such as the
synchronous precursor selection (SPS) tandem MS/MS/MS (MS3) approach, enable
maintenance of reporter ion accuracy and precision by reducing the ratio
compression caused by coisolated precursor ions. However, the decreased
throughput of the MS3 approach necessitates careful optimization of acquisition
strategies and methods to ensure maximal proteome coverage. We present a
systematic analysis of acquisition parameters used to analyze isobaric-tagged
peptide samples on current generation Orbitrap mass spectrometer (MS) hardware.
In contrast with previously reported works, we demonstrate the limited utility of
acquiring reporter ion data in the ion trap analyzer; ion trap acquisition had
only a minimal increase in identification depth and reduced quantification
precision. We establish that despite the significantly increased scan rate
afforded through the use of higher energy collisional dissociation (HCD) in MS3
based ion trap isobaric tag analyses, the reduced quantification precision and
reporter ion yields negate the potential benefits in proteome coverage. Lastly,
using optimized parameter sets, we further demonstrate the limited utility of the
ion trap detector versus the Orbitrap for reporter ion detection in an in-depth
analysis of a complex proteome sample. Together, these data will serve as a
valuable resource to researchers undertaking analysis on current generation
Orbitrap instrumentation with isobaric tags.
PMID- 28418258
TI - High Thermoelectric Performance in Electron-Doped AgBi3S5 with Ultralow Thermal
Conductivity.
AB - We report electron-doped AgBi3S5 as a new high-performance nontoxic
thermoelectric material. This compound features exceptionally low lattice thermal
conductivities of 0.5-0.3 W m-1 K-1 in the temperature range of 300-800 K, which
is ascribed to its unusual vibrational properties: "double rattling" phonon modes
associated with Ag and Bi atoms. Chlorine doping at anion sites acts as an
efficient electron donor, significantly enhancing the electrical properties of
AgBi3S5. In the carrier concentration range (5 * 1018-2 * 1019 cm-3) investigated
in this study, the trends in Seebeck coefficient can be reasonably understood
using a single parabolic band model with the electron effective mass of 0.22 me
(me is the free electron mass). Samples of 0.33% Cl-doped AgBi3S5 prepared by
spark plasma sintering show a thermoelectric figure of merit of ~1.0 at 800 K.
PMID- 28418259
TI - Signature of Congregated Effects of Mechanical and Electrical Anharmonicities,
Fermi Resonances, and Dampings on the IR Spectra of Hydrogen Bonded Systems:
Quantum Dynamic Study.
AB - Theoretical IR spectral density of the high-frequency stretching mode of hydrogen
bond (H-bond) systems is reported using a three-dimensional approach. The model,
studied within the framework of linear response theory, involves the mechanical
anharmonicity of the high-frequency stretching mode by contemplating its
potential as an asymmetric double well potential, the mechanical anharmonicity of
the H-bond Bridge by contemplating its potential as a Morse potential, Fermi
resonances which occur between the high frequency stretching mode and the
overtones of the bending modes, the electrical anharmonicity translated by the
nonlinearity to second order in the electric dipole moment function of the fast
mode, the second order modulation of the angular frequency and the equilibrium
position of the fast mode on the slow mode coordinate, and direct and indirect
relaxation mechanism. Moreover, the repulsive potential interposing in the fast
mode potential is chosen in Gaussian form to account for the asymmetry of the
fast mode potential and thereby elucidate the nature of the H-bond. The
anharmonic coupling between the fast and slow frequency modes is handled within
the strong anharmonic coupling theory. The direct relaxation of the fast mode and
the indirect relaxation of the H-bond Bridge are consolidated using previous
results [Rekik et al. Chem. Phys. 2008, 352, 65-76]. The infrared spectral
density is calculated using the Fourier transform of the autocorrelation function
of the transition dipole moment operator of the fast mode. The evolution of the
infrared absorption is demonstrated, indicating that mixing of all these effects
results in a broadening and complicated distribution of the spectral density. The
result of this work underscores the necessity of simultaneously combining the
maximum effects in H-bonded complexes for effectively modeling and interpreting
their corresponding IR spectra.
PMID- 28418260
TI - Fine Tuning of Multicolored Photoluminescence in Crystalline Magnetic Materials
Constructed of Trimetallic EuxTb1-x[Co(CN)6] Cyanido-Bridged Chains.
AB - Coordination compounds built of trivalent lanthanide ions have been demonstrated
as promising solid-state materials for diverse photoluminescent applications and
as attractive magnetic objects with the prospective application in information
storage and spintronics. We present a synthetic methodology in which both
luminescent and magnetic functionalities are induced within lanthanide-based
coordination polymers by the application of hexacyanocobaltate(III) anions and 3
hydroxypyridine (3-OHpy), both coordinated to 4f-metal ions modulating the
lanthanide-centered properties. We report a series of trimetallic cyanido-bridged
chains {[EuIIIxTbIII1-x(3-OHpy)2(H2O)4][CoIII(CN)6]}.H2O (x = 1, 0.8, 0.5, 0.4,
0.3, 0.2, 0.1, 0; compounds 1, 2, ..., 7, 8). They reveal tunable visible
photoluminescence ranging from green, through yellow and orange, to red color
depending on the composition of material and the wavelength of UV excitation
light. Such multicolored emission is realized by the adjusted ratio between red
emissive Eu3+ and green emissive Tb3+ and by the selection of wavelengths of UV
light controlling the intensities of Eu- and Tb-based components of visible
luminescence. The photoluminescence is enhanced by the energy-transfer (ET)
process from [CoIII(CN)6]3- and 3-OHpy to lanthanides, and the efficiencies of ET
to Eu and Tb play an important role in the switchable emission. The whole family,
1-8, exhibits temperature-dependent paramagnetism due to the intrinsic property
of lanthanide(3+) ions. Tb-containing 2-8 reveal the field-induced slow
relaxation of magnetization due to the magnetic anisotropy of Tb3+. Moreover, the
compounds built of large amounts of Tb reveal the double relaxation, the faster
of a typical TbIII single-ion origin, and the slower originating from the
magnetic dipole-magnetic dipole interactions between neighboring TbIII centers.
Compound 2, which can be considered as a magnetically diluted sample, exhibits
almost single relaxation process with the thermal energy barrier DeltaE/kB of
35.8(6) K and tau0 = 1.1(2) * 10-8 s at Hdc = 1500 Oe, indicating a single
molecule magnet behavior.
PMID- 28418261
TI - Preschool children's communication, motor and social development: Parents' and
educators' concerns.
AB - PURPOSE: During early childhood, it is important to identify which children
require intervention before they face the increased demands of school. This study
aimed to: (1) compare parents' and educators' concerns, (2) examine inter-rater
reliability between parents' and educators' concerns and (3) determine the group
difference between level of concern and children's performance on clinical
testing. METHOD: Parents and educators of 1205 4- to 5-year-old children in the
Sound Start Study completed the Parents' Evaluation of Developmental Status.
Children whose parents/educators were concerned about speech and language
underwent direct assessment measuring speech accuracy (n = 275), receptive
vocabulary (n = 131) and language (n = 274). RESULT: More parents/educators were
concerned about children's speech and expressive language, than behaviour, social
emotional, school readiness, receptive language, self-help, fine motor and gross
motor skills. Parents' and educators' responses were significantly correlated
(except gross motor). Parents' and educators' level of concern about expressive
speech and language was significantly correlated with speech accuracy on direct
assessment. Educators' level of concern was significantly correlated with a
screening measure of language. Scores on a test of receptive vocabulary
significantly differed between those with concern and those without. CONCLUSION:
Children's communication skills concerned more parents and educators than other
aspects of development and these concerns generally aligned with clinical
testing.
PMID- 28418262
TI - Adherence and persistence in patients with type 2 diabetes mellitus newly
initiating canagliflozin, dapagliflozin, dpp-4s, or glp-1s in the United States.
AB - OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors were first approved in the
US in 2013; therefore, real-world (RW) studies describing outcomes are limited.
This retrospective study evaluated adherence and persistence among patients
initiating canagliflozin (CANA), dapagliflozin (DAPA), GLP-1 agonists (GLP-1s),
and DPP-4 inhibitors (DPP-4s) over a 12-month follow-up from a US managed care
perspective. METHODS: Patients newly initiating CANA, DAPA, GLP-1s, or DPP-4s
from February 1, 2014-June 30, 2014 were identified from the QuintilesIMS
PharMetrics Plus Database. The first fill defined the index date/drug. Patients
were required to have a T2DM diagnosis (ICD-9-CM 250.x[0,2]) and >=12 months of
continuous enrollment pre- and post-index (follow-up). Main outcome measures were
adherence (proportion of days covered, PDC; medication possession ratio, MPR) and
persistence on index therapy. PDC or MPR >=0.80 was considered adherent. Patients
were considered persistent until evidence of discontinuation (gap >=90 days
between two subsequent index therapy prescriptions). Kaplan-Meier (KM) analysis
assessed time to discontinuation, while a Cox proportional hazards model (PHM)
evaluated risk of discontinuation. Logistic regression models evaluated the
likelihood of non-adherence. RESULTS: The final sample consisted of 23,702
patients (6,546 CANA, 3,087 DAPA, 6,273 GLP-1s, and 7,796 DPP-4s; 56% male, and
mean [SD] age = 55 [9.1] years). Mean PDC ranged from 0.56 (GLP-1), to 0.71
(CANA), with 33-56% adherent, respectively; MPR results were similar. Fifty-two
per cent (GLP-1) to 68% (CANA) were persistent over the follow-up. CANA patients
had the longest time to discontinuation. In regression analyses, compared to CANA
100 mg, DAPA, DPP-4, and GLP-1 patients had a significantly higher likelihood of
non-adherence and a significantly higher risk of discontinuation. CANA 300 mg
patients had a significantly lower likelihood of non-adherence and a
significantly lower risk of discontinuation compared to CANA 100 mg. CONCLUSIONS:
Adherence and persistence were significantly better with CANA (100 mg and 300 mg)
compared to DAPA, GLP-1s, and DPP-4s in the RW setting.
PMID- 28418263
TI - Systematic bias in predictions of new drugs' budget impact: analysis of a sample
of recent US drug launches.
AB - OBJECTIVE: Expectations about the budget impact of new drug launches may affect
payer behavior and ultimately consumer costs. Therefore, we evaluated the
accuracy of pre-launch US budget impact estimates for a sample of new drugs.
METHODS: We searched for publicly available budget impact estimates made pre
launch for drugs approved in the US from 1 September 2010 to 1 September 2015 and
compared them to actual sales. Accuracy was calculated as the ratio of pre-launch
estimate to actual sales. Quantitative analyses, including multivariate
regressions, were used to identify factors associated with accuracy. RESULTS: We
identified 25 budget impact estimates: 23 for one of 14 individual drugs and 2
for the category of PCSK9 inhibitors. The ratios of predicted to actual budget
impact ranged from 0.2 (estimate was 20% of sales) for secukinumab to 37.5
(estimate was 37.5 * sales) for PCSK9 inhibitors. Mean ratio was 5.5. In
multivariate analyses, larger eligible population, more recent estimate year
(e.g. 2015 vs. 2012), and being first in class, were associated with
statistically significant, greater overestimation of budget impact. CONCLUSIONS:
For every $5.5 of predicted cost, there was $1 of actual cost to the healthcare
system. This study, although based on a small, non-random sample, suggests
possible cognitive bias on the part of the estimators. Overestimating budget
impact may lead to early access restrictions, higher copays, and other changes
that ultimately impact patients. Analysts and non-profits should be attuned to
likely sources of error in order to improve their predictions.
PMID- 28418264
TI - Emission Characteristics of Laser-Induced Plasma Using Collinear Long and Short
Dual-Pulse Laser-Induced Breakdown Spectroscopy (LIBS).
AB - Collinear long and short dual-pulse laser-induced breakdown spectroscopy (DP
LIBS) was employed to clarify the emission characteristics from laser-induced
plasma. The plasma was sustained and became stable by the long pulse-width laser
with the pulse width of 60 MUs under free running (FR) conditions as an external
energy source. Comparing the measurement results of stainless steel in air using
single-pulse LIBS (SP-LIBS) and DP-LIBS, the emission intensity was markedly
enhanced using DP-LIBS. The temperature of plasma induced by DP-LIBS was
maintained at a higher temperature under different gate delay time and short
pulse-width laser power conditions compared with those measured using short SP
LIBS. Moreover, the variation rates of plasma temperatures measured using DP-LIBS
were also lower. The superior detection ability was verified by the measurement
of aluminum sample in water. The spectra were clearly detected using DP-LIBS,
whereas it cannot be identified using SP-LIBS of short and long pulse widths. The
effects of gate delay time and short pulse-width laser power were also discussed.
These results demonstrate the feasibility and enhanced detection ability of the
proposed collinear long and short DP-LIBS method.
PMID- 28418265
TI - Global health resource utilization associated with pacemaker complications.
AB - AIM: To estimate health resource utilization (HRU) associated with the management
of pacemaker complications in various healthcare systems. METHODS:
Electrophysiologists (EPs) from four geographical regions (Western Europe,
Australia, Japan, and North America) were invited to participate. Survey
questions focused on HRU in the management of three chronic pacemaker
complications (i.e. pacemaker infections requiring extraction, lead
fractures/insulation breaches requiring replacement, and upper extremity deep
venous thrombosis [DVT]). Panelists completed a maximum of two web-based surveys
(iterative rounds). Mean, median values, and interquartile ranges were calculated
and used to establish consensus. RESULTS: Overall, 32 and 29 panelists
participated in the first and second rounds of the Delphi panel, respectively.
Consensus was reached on treatment and HRU associated with a typical pacemaker
implantation and complications. HRU was similar across regions, except for Japan,
where panelists reported the longest duration of hospital stay in all scenarios.
Infections were the most resource-intensive complications and were characterized
by intravenous antibiotics days of 9.6?13.5 days and 21.3?29.2 days for pocket
and lead infections respectively; laboratory and diagnostic tests, and system
extraction and replacement procedures. DVT, on the other hand, was the least
resource intensive complication. LIMITATIONS: The results of the panel represent
the views of the respondents who participated and may not be generalizable
outside of this panel. The surveys were limited in scope and, therefore, did not
include questions on management of acute complications (e.g. hematoma,
pneumothorax). CONCLUSIONS: The Delphi technique provided a reliable and
efficient approach to estimating resource utilization associated with chronic
pacemaker complications. Estimates from the Delphi panel can be used to generate
costs of pacemaker complications in various regions.
PMID- 28418269
TI - Is a hollow centralizer necessary when using a polished, tapered, cemented
femoral stem?
AB - Background and purpose - A tapered, polished and collarless stem is normally
equipped with a hollow centralizer to prevent the stem from becoming end-bearing
in the cement as the stem subsides. In a randomized clinical trial, we evaluated
such a stem (MS-30), which was initially introduced with a solid centralizer but
was later recommended to be fitted with a hollow centralizer. We hypothesized
that while the stem would sink more, it would become rotationally stable and have
less retroversion with a hollow centralizer than with a solid centralizer.
Patients and methods - We randomized 60 patients with primary hip arthritis to
receive either a hollow centralizer or a solid centralizer with the stem. The
effect was evaluated over a 10-year follow-up period with repeated RSA
examinations, conventional radiographs, and clinical follow-ups using the WOMAC
and SF-12 questionnaires. Results - At 10-year follow-up, the group with hollow
centralizers had subsided more than the group with solid centralizers (1.99 mm
(hollow) as opposed to 0.57 mm (solid); p < 0.001). However, rotation was similar
at 10-year follow-up (mean retroversion 1.34 degrees (hollow) and 1.30 degrees
(solid)). Both groups showed excellent 10-year results, with similar clinical
outcome, and none of the stems were radiographically loose or had been revised.
Interpretation - As expected, there was more subsidence in the group with hollow
centralizers, and with similar magnitude to that reported in earlier RSA studies
on conceptually similar prostheses. Interestingly, there was no difference in the
rotational behavior of the prostheses. This stem type appears to have a design
that, regardless of the type of centralizer and the possibility of subsidence,
withstands the rotational forces it is subjected to very well. This study does
not support the need for a hollow centralizer for these types of stems.
PMID- 28418267
TI - BTKC481S-Mediated Resistance to Ibrutinib in Chronic Lymphocytic Leukemia.
AB - Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in
chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse
has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can
cause relapse, but data regarding the prevalence and natural history of these
mutations are limited. Patients and Methods Patients accrued to four sequential
studies of ibrutinib were included in these analyses. Deep sequencing for BTK and
PLCG2 was performed retrospectively on patients who experienced relapse and
prospectively on a screening population. Results With a median follow-up time of
3.4 years, the estimated cumulative incidence of progression at 4 years is 19%
(95% CI, 14% to 24%). Baseline karyotypic complexity, presence of del(17)(p13.1),
and age less than 65 years were risk factors for progression. Among patients who
experienced relapse, acquired mutations of BTK or PLCG2 were found in 85% (95%
CI, 71% to 94%), and these mutations were detected an estimated median of 9.3
months (95% CI, 7.6 to 11.7 months) before relapse. Of a group of 112 patients
examined prospectively, eight patients have experienced relapse, and all of these
patients had acquired resistance mutations before relapse. A resistance mutation
was detected in an additional eight patients who have not yet met criteria for
clinical relapse. Conclusion Relapse of chronic lymphocytic leukemia after
ibrutinib is an issue of increasing clinical significance. We show that mutations
in BTK and PLCG2 appear early and have the potential to be used as a biomarker
for future relapse, suggesting an opportunity for intervention.
PMID- 28418268
TI - The folding competence of HIV-1 Tat mediated by interaction with TAR RNA.
AB - The trans-activator Tat protein of HIV-1 belongs to the large family of
intrinsically disordered proteins (IDPs), and is known to recruit various host
proteins for the transactivation of viral RNA synthesis. Tat protein interacts
with the transactivator response RNA (TAR RNA), exhibiting RNA chaperone
activities for structural rearrangement of interacting RNAs. Here, considering
that Tat-TAR RNA interaction is mutually cooperative, we examined the potential
role of TAR RNA as Chaperna - RNA that provides chaperone function to proteins -
for the folding of HIV-1 Tat. Using EGFP fusion as an indirect indicator for
folding status, we monitored Tat-EGFP folding in HeLa cells via time-lapse
fluorescence microscopy. The live cell imaging showed that the rate and the
extent of folding of Tat-EGFP were stimulated by TAR RNA. The purified Tat-EGFP
was denatured and the fluorescence was monitored in vitro under renaturation
condition. The fluorescence was significantly increased by TAR RNA, and the
mutations in TAR RNA that affected the interaction with Tat protein failed to
promote Tat refolding. The results suggest that TAR RNA stabilizes Tat as
unfolded, but prevents it from misfolding, and maintaining its folding competence
for interaction with multiple host factors toward its transactivation. The
Chaperna function of virally encoded RNA in establishing proteome link at the
viral-host interface provides new insights to as yet largely unexplored RNA
mediated protein folding in normal and dysregulated cellular metabolism.
PMID- 28418270
TI - USMLE and Otolaryngology: Predicting Board Performance.
AB - Objective To ascertain what relationship exists between the United States Medical
Licensing Examination (USMLE) and the American Board of Otolaryngology Written
Qualifying Examination (WQE). Study Design Retrospective, longitudinal study.
Setting De-identified database. Subjects Residents entering otolaryngology-head
and neck surgery (OHNS) residency between 2007 and 2009 and taking the WQE for
the first time between 2012 and 2014. Methods Regression models were used to
determine if the USMLE score predicts passage of the WQE on the first attempt,
which step score was a better predictor, and whether an increase in the Step 2
score increased the chances of WQE passage. Results There were 611 Step 1 and 402
Step 2 scores. Mean (SD) Step 1 score was 238 (14.4), and the mean (SD) Step 2
score was 243 (16.8). The overall WQE first-time passage rate was 95.3%. Step 1
score was a better predictor than Step 2 for successful passage of the WQE on the
first attempt ( P = .0026). An increase in the Step 2 score compared with the
Step 1 score did not predict an improved first-time passage rate on the WQE.
Conclusions There is an association between USMLE scores and successful first
time passage of the WQE, with Step 1 being a stronger predictor than Step 2.
Residents with USMLE scores lower than the average successful OHNS applicant
still have a high chance of passing the WQE. USMLE scores alone are of limited
usefulness in identifying those applicants at risk of failing the WQE on the
first attempt.
PMID- 28418271
TI - Use of a Novel Airway Kit and Simulation in Resident Training on Emergent
Pediatric Airways.
AB - Objective Development of a novel pediatric airway kit and implementation with
simulation to improve resident response to emergencies with the goal of improving
patient safety. Methods Prospective study with 9 otolaryngology residents
(postgraduate years 1-5) from our tertiary care institution. Nine simulated
pediatric emergency airway drills were carried out with the existing system and a
novel portable airway kit. Response times and time to successful airway control
were noted with both the extant airway system and the new handheld kit. Results
were analyzed to ensure parametric data and compared with t tests. A Bonferroni
adjustment indicated that an alpha of 0.025 was needed for significance. Results
Use of the airway kit significantly reduced the mean time of resident arrival by
47% ( P = .013) and mean time of successful intubation by 50% ( P = .007). Survey
data indicated 100% improved resident comfort with emergent airway scenarios with
use of the kit. Discussion Times to response and meaningful intervention were
significantly reduced with implementation of the handheld airway kit. Use of
simulation training to implement the new kit improved residents' comfort and
airway skills. This study describes an affordable novel mobile airway kit and
demonstrates its ability to improve response times. Implications for Practice The
low cost of this airway kit makes it a tenable option even for smaller hospitals.
Simulation provides a safe and effective way to familiarize oneself with novel
equipment, and, when possible, realistic emergent airway simulations should be
used to improve provider performance.
PMID- 28418272
TI - Incubation Temperature Alters Temperature-Dependent Oxygen Consumption in
Northern Bobwhite Quail Hatchlings (Colinus virginianus).
AB - This study investigated the effect of mismatching incubation and posthatch
temperatures in northern bobwhite quail hatchlings. Quail embryos were incubated
at 35.5 degrees or 37.5 degrees C. Metabolic rates were then measured in
hatchlings acclimated to either the same or the opposite temperature treatment.
While hatchlings expressed higher oxygen consumption when posthatch temperature
did not match incubation temperature, the effect of mismatching temperatures was
significant only when posthatch temperature was higher than incubation
temperature. Our data suggest that bobwhite quail hatchlings may express
increased metabolism due to mismatches between incubation and posthatch
temperatures. More specifically, the nature or direction of the mismatch can
determine the magnitude of the metabolic effect. These findings highlight the
importance of considering the context of specific conditions experienced
throughout ontogeny when observing phenotypic outcomes.
PMID- 28418273
TI - Thalidomide for Epistaxis in Patients with Hereditary Hemorrhagic Telangiectasia:
A Preliminary Study.
AB - To evaluate the effectiveness of thalidomide for epistaxis in hereditary
hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were
treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to
100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the
treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after
starting thalidomide. The mean ESS before treatment, at the end of treatment, and
3 months after stopping treatment was 5.03 +/- 2.05, 0.90 +/- 0.84 ( P = .003),
and 1.98 +/- 1.33 ( P = .006), respectively. Four patients reported mild to
moderate side effects, including drowsiness, dizziness, constipation, nausea, and
peripheral neuropathy. Two patients stopped the treatment because of adverse
effects. Those results showed that thalidomide may be a treatment choice for
recurrent epistaxis in HHT patients, although the side effects should be
considered. Further study should focus on guidelines for dosing and course and
investigate how to reduce the adverse effects.
PMID- 28418275
TI - Factors Influencing Cochlear Patency after Translabyrinthine Surgery.
AB - Objective To determine predictive factors for cochlear obliteration after
translabyrinthine surgery for vestibular schwannoma. Study Design Case series
with chart review. Setting Neurotology referral center. Subjects and Methods In
total, 345 charts were reviewed, resulting in 103 patients who underwent
translabyrinthine surgery between January 2010 and July 2015 and had
postoperative magnetic resonance imaging (MRI) for review. Surveillance MRI
performed after translabyrinthine resection of vestibular schwannomas was
reviewed. Heavily T2-weighted MRI obtained an average of 21.8 months after
surgery was reviewed to assess cochlear patency. Tumor size, preoperative
audiograms, and MRI cochlear fluid-attenuated inversion recovery (FLAIR)
intensity were compared between patients with retained cochlear patency and those
without. Results Fifty-four percent of patients retained cochlear patency after
translabyrinthine surgery. Tumor size did not differ statistically between the 2
groups. There was no statistically significant difference in speech reception
thresholds, pure-tone average, or word recognition scores between patent and
nonpatent groups. Preoperative MRI FLAIR intensity did not differ between groups.
Conclusions More than half of patients retain cochlear patency after
translabyrinthine vestibular schwannoma surgery. Cochlear patency is required for
cochlear implant in patients with unilateral deafness. Preoperative tumor size,
hearing performance, and intensity on MRI FLAIR do not predict cochlear patency.
To prevent loss of opportunity for cochlear implantation, simultaneous
implantation and cochlear lumen keeper placement are options.
PMID- 28418274
TI - The Gulf Long-Term Follow-Up Study (GuLF STUDY): Biospecimen collection at
enrollment.
AB - The 2010 Deepwater Horizon (DWH) explosion in the Gulf of Mexico led to the
largest ever marine oil spill by volume. The GuLF STUDY is investigating possible
adverse human health effects associated with oil spill activities. One objective
of the study was to utilize biological specimens from study participants to
examine spill-related adverse health effects. This study describes the methods
for collecting, processing, shipping, and storing specimens during the enrollment
phase of the study. GuLF STUDY participants living in Gulf States (Alabama,
Florida, Louisiana, Mississippi, and eastern Texas) were eligible to complete a
home visit at enrollment, one to three years after the DWH explosion. During this
visit, blood, urine, toenail and hair clippings, and house dust samples were
collected. Specimens were shipped overnight to a central processing laboratory in
containers with cold and ambient temperature compartments. Most blood and urine
specimens were then aliquoted and stored in liquid nitrogen vapor or at -80
degrees C, with some samples stored at -20 degrees C. A total of 11,193
participants completed a home visit, and over 99% provided at least one
biospecimen. Most participants provided blood (93%), urine (99%), and toenail
clippings (89%), and 40% provided hair. Nearly all participants (95%) provided
house-dust samples. Most samples were received by the laboratory one (58%) or two
(25%) days after collection. These biospecimens enable investigation of a range
of biomarkers of spill-related adverse health effects, and possibly some
biomarkers of spill-related exposures. The biospecimen collection, handling, and
storage protocols were designed to maximize current and future scientific value
within logistical and budgetary constraints and might serve as a template for
future studies conducted in similar time-critical and geographically dispersed
settings.
PMID- 28418276
TI - Thrombin-antithrombin III complex tests.
AB - PURPOSE: Patients with fractures of the pelvis and/or lower extremities are at a
high risk of developing postoperative venous thromboembolism (VTE). The purpose
of this study was to determine whether the thrombin-antithrombin III complex
(TAT) tests could be used for postoperative screening of VTE in patients with
lower limb or pelvic fractures. METHODS: We enrolled 133 patients who underwent
surgical treatment for fracture of the pelvis or lower extremities. TAT and D
dimer levels were compared in patients with and without VTE. Receiver operating
characteristic (ROC) curve analysis was done and the appropriate TAT and D-dimer
cutoff levels were determined for VTE screening. RESULTS: VTE was diagnosed in 41
patients (30.8%). Patients with VTE had significantly higher levels of TAT and D
dimer on postoperative days 1, 3, and 7 than those without VTE, respectively. ROC
curve analysis suggested that TAT test at postoperative day 7 had the highest
accuracy for predicting postoperative VTE. With the optimal cutoff TAT level of
3.0 ng/mL, sensitivity and specificity were 93.3% and 70.1%, respectively. With
the optimal cutoff D-dimer level of 7.4 ug/mL, sensitivity and specificity were
93.3% and 57.0%, respectively. CONCLUSION: TAT levels measured at postoperative
day 7 could be the most useful parameter for screening postoperative VTE. TAT can
be used as a screening tool for screening postoperative VTE in patients with
lower limb and pelvic fractures.
PMID- 28418277
TI - Geographical variation in the skeletal morphology of red jungle fowl.
AB - 1. The skulls and postcranial skeletons of the red jungle fowl (Gallus gallus)
were compared osteometrically between the populations from North and South
Vietnam, North and Central Laos and Southeast Bangladesh. The populations include
the three subspecies of G. g. spadiceus, G. g. gallus and G. g. murghi and were
sampled to reveal the geographical morphological variations among populations in
G. gallus. 2. The morphometric characteristics of subspecies murghi could be
clearly distinguished from those of the other subspecies using a canonical
discriminant analysis. However, the size and shape of the skull of the gallus
population from South Vietnam were not statistically different from that of the
subspecies spadiceus from North Laos. The canonical discriminant scores also
clearly indicated that there were morphological similarities in the skulls of the
populations from North Laos and South Vietnam. 3. From the results, therefore, it
is concluded that red jungle fowls do not exhibit high levels of osteometric
variation between geographical localities at least within the Indochinese
Peninsula. 4. This contrasts with previous studies which have described these
subspecies as having various external morphological differences and have argued
that zoogeographical barriers exist between the north and south areas of the
Indochinese Peninsula.
PMID- 28418278
TI - The Effect of Surgical Insertion and Proinflammatory Cytokines on Osteochondral
Allograft Survival and Metabolism.
AB - Objective To investigate the responses of refrigerated osteochondral allograft
cartilage (OCA) and fresh cartilage (FC), including cell survival and metabolism,
to surgical impaction and proinflammatory cytokines. Design Osteochondral plugs
(8 mm diameter) were harvested from prolonged-refrigerated (14-28 days) and fresh
(<=24 hours postmortem) human femoral hemicondyles and subjected to a 0.2 N s
pneumatic impaction impulse. Cartilage explants were removed from subchondral
bone and randomized to 1 of 6 treatment groups: (1) Unimpacted control (UIC), (2)
Impacted control (IC), (3) Impacted + interleukin (IL)-1beta (0.1 ng/mL), (4)
Impacted + IL-1beta (0.1 ng/mL) + IL-6, (5) Impacted + IL-1beta (10 ng/mL), and
(6) Impacted + IL-1beta (10 ng/mL) + IL-6. Samples were measured for cell
viability, histology, and proteoglycan (PG) content at days 0, 2, 7, and 14 of
culture. Results In UIC, cell viability was indistinguishable between OCA and FC
and remained constant. Impaction alone decreased cell viability by 30% ( P <
0.01) in the OCA superficial layer and by 26% ( P < 0.01) in the entire tissue,
but did not affect viability in FC. Cytokine addition did not further influence
cell viability. Impaction alone did not affect PG synthesis. Addition of
cytokines to impacted tissue decreased PG synthesis by ~3-fold in both tissue
types in comparison with corresponding impacted controls ( P < 0.01). Throughout
2-week culture, PG release remained stable in all FC groups, but peaked at day 14
in OCA cartilage subjected to cytokines. Conclusions Mechanical impaction,
mimicking surgical insertion, has a more profound effect on cell viability in OCA
than in FC. Addition of proinflammatory cytokines further decreases OCA tissue
metabolism and integrity.
PMID- 28418279
TI - Intersectional stigma among midlife and older Black women living with HIV.
AB - HIV-related stigma is a barrier to the prevention and treatment of HIV. For
midlife and older Black women, the nature and intensity of HIV-related stigma may
be compounded by their multiple marginalised social status based on gender, race,
and age. We examined the perceptions and experiences of HIV-related stigma among
midlife and older Black women living in Prince George's County, Maryland, USA.
Between 2014 and 2015, we conducted semi-structured interviews with a sample of
35 midlife and older Black women living with HIV. Using a modified grounded
theory approach, we explored emergent themes related to the manifestation and
experience of intersectional stigma and changes in stigma experience over time.
Our findings suggest that intersectional stigma is a central feature in midlife
and older Black women's lives, with women reporting experiences of intersectional
stigma at the interpersonal/familial, community, and institutional/structural
levels. Although women acknowledged gradual acceptance of their HIV-positive
status over time, they continued to experience negative responses related to
gender, race, age, and disease. Our findings indicate that a more robust
understanding of the impact of HIV-related stigma requires work to consider the
complex manifestations of intersectional stigma among an increasingly aging
population of Black women in the USA.
PMID- 28418280
TI - Twenty-First Century Pathologists' Advocacy.
AB - Pathologists' advocacy plays a central role in the establishment of continuously
improving patient care quality and patient safety, and in the maintenance and
progress of pathology as a profession. Pathology advocacy's primary goal is the
betterment of patient safety and quality medical care; however, payment is a
necessary and appropriate component to both, and has a central role in advocacy.
Now is the time to become involved in pathology advocacy; the Medicare Access and
Children's Health Insurance Program (CHIP) Reauthorization Act of 2015 (MACRA)
and the Protecting Access to Medicare Act of 2014 (PAMA) are 2 of the most
consequential pieces of legislation impacting the pathology and laboratory
industry in the last 20 years. Another current issue of far-reaching impact for
pathologists is balance billing, and yet many pathologists have little or no
understanding of balance billing. Pathologists at all stages of their careers,
and in every professional setting, need to participate. Academic pathologists
have a special obligation to, if not become directly involved in advocacy, at
least have a broad and current understanding of those issues, as well as the need
and responsibility of pathologists to actively engage in advocacy efforts to
address them, in order to teach residents the place of advocacy, and its value,
as an inseparable and indispensable component of their professional
responsibilities.
PMID- 28418281
TI - Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1
(PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.
AB - CONTEXT: - Immune checkpoint pathways, including programmed death receptor
1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important
in mediating self-tolerance and controlling self-damage, can sometimes be
manipulated by cancer cells to evade immune surveillance. Recent clinical trials
further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various
cancers and reveal a new era of cancer immunotherapy. OBJECTIVE: - To review the
mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD
1/PD-L1 as a predictive and/or prognostic marker in various cancers, and
strategies of measuring PD-L1 expression. DATA SOURCES: - Representative medical
literature regarding PD-L1 expression in various cancers, including the
preliminary results of the Blue Proposal, which compares different
immunohistochemical stains for PD-L1 reported in the recent American Association
of Cancer Research (AACR) Annual Meeting (April 16-20, 2016). CONCLUSION: -
Either PD-1/PD-L1-targeted therapy alone or in combination with other treatment
modalities provides benefit for patients with advanced cancers. Because of the
complexity of cancer immunity, we still do not have a reliable biomarker to
predict the response of PD-1/PD-L1-targeted therapy. Future studies, including
methods beyond immunohistochemical stains, are needed to develop reliable
biomarker/biomarkers for pathology laboratories to aid in selecting patients who
will benefit most from PD-1/PD-L1-targeted therapy.
PMID- 28418283
TI - Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.
AB - CONTEXT: - Bilirubin has strong anti-inflammatory and antioxidative stress
action. Progression of inflammation involving arteries is a crucial activator in
pathogenesis of Takayasu arteritis (TA). OBJECTIVE: - To investigate the
relationship between serum bilirubin and TA. DESIGN: - Our study involved 115
consecutive TA patients. Patients with active-phase disease were followed and
received prednisone therapy. RESULTS: - Lower concentrations of serum bilirubin
were detected in TA patients compared with healthy subjects (0.6 +/- 0.31 versus
0.7 +/- 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA
patients were lower than those in inactive patients (0.5 +/- 0.20 versus 0.8 +/-
0.32 mg/dL, P < .001). In all patients with TA, serum bilirubin correlated
positively with total protein (r = 0.193, P = .04) and negatively with C-reactive
protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532,
P < .001, respectively). Multiple logistic regression analysis showed that each
decrease of 1 mg/dL in serum bilirubin was associated with a 1.10 times increase
in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856
0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation
rate (beta = -0.170, P < .001) in multiple linear regression analysis. The area
under the curve for serum bilirubin in predicting active TA patients was 0.802.
Serum bilirubin levels were found to be significantly increased after prednisone
treatment (0.5 +/- 0.20 versus 0.7 +/- 0.15 mg/dL, P = .002). CONCLUSIONS: -
Lower serum bilirubin levels are associated with TA, and serum bilirubin may be
influenced by prednisone therapy in active TA patients. Serum bilirubin levels in
TA patients correlate negatively with erythrocyte sedimentation rate.
PMID- 28418282
TI - Immunohistochemical Detection of Hairy Cell Leukemia in Paraffin Sections: The
Role of Pax5 and CD103 Double Staining to Improve Specificity and Sensitivity.
AB - CONTEXT: - In hematopathology practice, abnormal expression of CD103 on B cells
is detected by flow cytometry in hairy cell leukemia (HCL) and, in combination
with other phenotypic and morphologic findings, provides diagnostic specificity
and sensitivity. Immunostaining on paraffin sections makes it possible to perform
immunophenotyping in situ. However, normal bone marrow contains CD103-positive
cells, which are not B cells, making it difficult to be certain about low-level
involvement by HCL. OBJECTIVE: - To develop dual immunostaining for confirmation
that CD103 is expressed in B cells, which may be highly desirable in assessing
low-level involvement by HCL. DESIGN: - We developed a dual immunostaining
approach using a B-cell marker, Pax5, expressed in the nucleus, in combination
with a membrane marker, CD103. RESULTS: - We analyzed 6 HCLs, 7 marginal zone
lymphomas, 12 lymphoplasmacytic lymphomas, 7 follicular lymphomas, 5 chronic
lymphocytic leukemias, 5 mantle cell lymphomas, 1 multiple myeloma (lymphocytic
variant), and 3 bone marrows not involved by any B-cell neoplasm. Our dual
staining approach confirmed that only the neoplastic cells of HCL were positive
for both CD103 and Pax5. CONCLUSIONS: - This dual-staining method is particularly
helpful in cases with low-level involvement by HCL and can be used for
determining minimal residual disease after treatment.
PMID- 28418285
TI - A new predictive tool for postoperative radiotherapy in prostate cancer.
AB - The standard treatments of localized prostate cancer include surgical resection
and/or radiotherapy. Recently in 2016, Zhao et al. described a tool to predict
which patients will most likely gain from postoperative radiotherapy. Such a
method can personalize treatment plan by maximizing benefit but minimizing harm.
PMID- 28418286
TI - External application of NF-kappaB inhibitor DHMEQ suppresses development of
atopic dermatitis-like lesions induced with DNCB/OX in BALB/c mice.
AB - CONTEXT: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as
an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of
NF-kappaB and has been shown to possess promising potential as an anti
inflammatory and anti-tumor agent. OBJECTIVE: This study examines DHMEQ's effect
on therapeutic potential for atopic dermatitis (AD)-like lesions. MATERIALS AND
METHODS: AD lesions were chronically induced by the repetitive and alternative
application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in
BALB/c mice. The mice were then externally treated with DHMEQ ointment.
Macroscopic and microscopic changes of the skin lesions were observed and
recorded. RESULTS: DHMEQ inhibited ear swelling and relieved clinical symptoms of
the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination
illustrated that it significantly decreased DNCB/OX-induced epidermal thickness,
the infiltration of inflammatory cells, and the count of mast cell. The elevated
level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon gamma
(IFN-gamma), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also
suppressed by DHMEQ. DISCUSSION AND CONCLUSION: This study indicated that DHMEQ
would be useful for the treatment of AD.
PMID- 28418287
TI - Synergistic Effect of Ischemic Preconditioning and Antithrombin in Ischemia
Reperfusion Injury.
AB - OBJECTIVES: Our study aimed to determine whether antithrombin plays a synergistic
role in accentuating the effects of intestinal ischemic preconditioning.
MATERIALS AND METHODS: Fifty rats were randomly allocated to 5 groups (10
rats/group) as follows: sham treatment (group 1); ischemia-reperfusion (group 2);
ischemic preconditioning followed by ischemia-reperfusion (group 3); antithrombin
+ ischemia-reperfusion, similar to group 2 but including antithrombin
administration (group 4); and antithrombin + ischemic preconditioning, similar to
group 3 but including antithrombin administration (group 5). Blood samples and
liver specimens were obtained for measurement of cytokines, myeloperoxidase, and
malondialdehyde. Liver biopsies were examined by electron microscopy. RESULTS:
Intestinal ischemia-reperfusion induced a remote hepatic inflammatory response as
evidenced by the striking increase of proinflammatory cytokines, myeloperoxidase,
and malondialdehyde. Tumor necrosis factor-alpha levels in group 5 (12.48 +/- 0.7
pg/mL) were significantly lower than in group 3 (13.64 +/- 0.78 pg/mL; P = .014).
Mean interleukin 1beta was lower in group 5 (9.52 +/- 0.67pg/mL) than in group 3
(11.05 +/- 1.9 pg/mL; P > .99). Mean interleukin 6 was also significantly lower
in group 5 (17.13 +/- 0.54 pg/mL) than in group 3 (23.82 +/- 1 pg/mL; P <= .001).
Myeloperoxidase levels were significantly higher in group 3 (20.52 +/- 2.26 U/g)
than in group 5 (18.59 +/- 1.03 U/g; P = .025). However, malondialdehyde levels
did not significantly improve in group 5 (4.55 +/- 0.46 MUmol) versus group 3
(5.17 +/- 0.61 MUmol; P = .286). Tumor necrosis factor-alpha, interleukin 6, and
myeloperoxidase findings show that antithrombin administration further attenuated
the inflammatory response caused by ischemia-reperfusion, suggesting a
synergistic effect with ischemic preconditioning. These findings were confirmed
by electron microscopy. CONCLUSIONS: The addition of antithrombin to ischemic
preconditioning may act to attenuate or prevent damage from ischemia-reperfusion
injury by inhibiting the release of cytokines and neutrophil infiltration.
PMID- 28418289
TI - Volatile organic compounds produced by a soil-isolate, Bacillus subtilis FA26
induce adverse ultra-structural changes to the cells of Clavibacter michiganensis
ssp. sepedonicus, the causal agent of bacterial ring rot of potato.
AB - Rhizobacterial volatile organic compounds (VOCs) play an important role in the
suppression of soil-borne phytopathogens. In this study, the VOCs produced by a
soil-isolate, Bacillus subtilis FA26, were evaluated in vitro for their
antibacterial activity against Clavibacter michiganensis ssp. sepedonicus (Cms),
the causal agent of bacterial ring rot of potato. The VOCs emitted by FA26
inhibited the growth of Cms significantly compared with the control. Scanning and
transmission electron microscopy analyses revealed distorted colony morphology
and a wide range of abnormalities in Cms cells exposed to the VOCs of FA26.
Varying the inoculation strategy and inoculum size showed that the production and
activity of the antibacterial VOCs of FA26 were dependent on the culture
conditions. Headspace solid-phase microextraction/gas chromatography-mass
spectrometry analyses revealed that FA26 produced 11 VOCs. Four VOCs
(benzaldehyde, nonanal, benzothiazole and acetophenone) were associated with the
antibacterial activity against Cms. The results suggested that the VOCs produced
by FA26 could control the causal agent of bacterial ring rot of potato. This
information will increase our understanding of the microbial interactions
mediated by VOCs in nature and aid the development of safer strategies for
controlling plant disease.
PMID- 28418288
TI - Immunopsychiatry: important facts.
AB - Accumulating evidence indicate a role for the immune system particularly
inflammation and autoimmunity in the aetiology of major psychiatric disorders
such as depression and schizophrenia. In this paper, we discuss some of the key
advances in immunopsychiatry in order to highlight to psychiatrists and other
health professionals how an increased understanding of this field might enhance
our knowledge of illness mechanism and approaches to treatment. We present a
brief overview of clinical research that link inflammation and autoimmunity with
depression and psychosis, including potential role of inflammation in treatment
response, current evidence for the effectiveness of immune-modulating treatment
for depression and psychosis, and possible role of inflammation in common
physical comorbidities for these disorders such as coronary heart disease and
diabetes mellitus. Gaining a better understanding of the role of immune system
could be paradigm changing for psychiatry. We need collaborations between
clinicians and scientists to deliver high-quality translational research in order
to fully realise the clinical potential of this exciting and rapidly expanding
field.
PMID- 28418290
TI - Invasive Nontuberculous Mycobacterial Infections among Cardiothoracic Surgical
Patients Exposed to Heater-Cooler Devices1.
AB - Invasive nontuberculous mycobacteria (NTM) infections may result from a
previously unrecognized source of transmission, heater-cooler devices (HCDs) used
during cardiac surgery. In July 2015, the Pennsylvania Department of Health
notified the Centers for Disease Control and Prevention (CDC) about a cluster of
NTM infections among cardiothoracic surgical patients at 1 hospital. We conducted
a case-control study to identify exposures causing infection, examining 11 case
patients and 48 control-patients. Eight (73%) case-patients had a clinical
specimen identified as Mycobacterium avium complex (MAC). HCD exposure was
associated with increased odds of invasive NTM infection; laboratory testing
identified patient isolates and HCD samples as closely related strains of M.
chimaera, a MAC species. This investigation confirmed a large US outbreak of
invasive MAC infections in a previously unaffected patient population and
suggested transmission occurred by aerosolization from HCDs. Recommendations have
been issued for enhanced surveillance to identify potential infections associated
with HCDs and measures to mitigate transmission risk.
PMID- 28418291
TI - Virulence Analysis of Bacillus cereus Isolated after Death of Preterm Neonates,
Nice, France, 2013.
AB - After the deaths of 2 preterm neonates with Bacillus cereus systemic infection in
the same intensive care unit, we investigated the pathogenic potential of this
bacterium. Genetic and virulence analysis indicated the neonates were infected
with 2 different strains with a virulence potential similar to environmental
strains, indicating likely patient immune response failure.
PMID- 28418292
TI - Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue
Virus Infection.
AB - Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect
Zika virus infection and confound serologic tests. Recent data demonstrate
neutralization of Zika virus by monoclonal antibodies or human serum collected
early after DENV infection. Whether this finding is true in late DENV
convalescence (>6 months after infection) is unknown. We studied late
convalescent serum samples from persons with prior DENV or Zika virus exposure.
Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was
not observed among primary DENV infections. We observed low-frequency (23%) Zika
virus cross-neutralization in repeat DENV infections. DENV-immune persons who had
Zika virus as a secondary infection had distinct populations of antibodies that
neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion
experiments. These data suggest that most DENV infections do not induce durable,
high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody
populations develop after Zika virus infection irrespective of prior DENV
immunity.
PMID- 28418293
TI - Insecticide-Treated Nets and Protection against Insecticide-Resistant Malaria
Vectors in Western Kenya.
AB - Insecticide resistance might reduce the efficacy of malaria vector control. In
2013 and 2014, malaria vectors from 50 villages, of varying pyrethroid
resistance, in western Kenya were assayed for resistance to deltamethrin. Long
lasting insecticide-treated nets (LLIN) were distributed to households at
universal coverage. Children were recruited into 2 cohorts, cleared of malaria
causing parasites, and tested every 2 weeks for reinfection. Infection incidence
rates for the 2 cohorts were 2.2 (95% CI 1.9-2.5) infections/person-year and 2.8
(95% CI 2.5-3.0) infections/person-year. LLIN users had lower infection rates
than non-LLIN users in both low-resistance (rate ratio 0.61, 95% CI 0.42-0.88)
and high-resistance (rate ratio 0.55, 95% CI 0.35-0.87) villages (p = 0.63). The
association between insecticide resistance and infection incidence was not
significant (p = 0.99). Although the incidence of infection was high among net
users, LLINs provided significant protection (p = 0.01) against infection with
malaria parasite regardless of vector insecticide resistance.
PMID- 28418294
TI - Exposure Risk for Infection and Lack of Human-to-Human Transmission of
Mycobacterium ulcerans Disease, Australia.
AB - We conducted epidemiologic and genetic analyses of family clusters of
Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found
that the incidence of M. ulcerans disease in family members was increased.
However, the risk for exposure appeared short-term and not related to human-human
transmission.
PMID- 28418295
TI - Phenotypic and Genotypic Shifts in Hepatitis B Virus in Treatment-Naive Patients,
Taiwan, 2008-2012.
AB - We examined the characteristic changes of hepatitis B virus (HBV) in antiviral
drug treatment-naive patients referred for pretreatment evaluation in Taiwan
during 2008-2012. Over time, we observed substantial decreases in the prevalence
of HBV e antigen (HBeAg) and increasing prevalence of the precore G1899A mutation
and HBV-DNA levels in HBeAg-positive patients.
PMID- 28418296
TI - Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination
Policy, China.
AB - China's hepatitis B virus (HBV) prevention policy has been evaluated through
nationally representative serologic surveys conducted in 1992 and 2006. We report
results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in
the context of program policy. The 2014 survey used a 2-stage sample strategy in
which townships were selected from 160 longstanding, nationally representative,
county-level disease surveillance points, and persons 1-29 years of age were
invited to participate. The 2014 sample size was 31,713; the response rate was
83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen
prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of
age, the decline was 97%. China's HBV prevention program, targeted toward
interrupting perinatal transmission, has been highly successful and increasingly
effective. However, this progress must be sustained for decades to come, and
elimination of HBV transmission will require augmented strategies.
PMID- 28418297
TI - Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999-2012.
AB - Survey results showed treponemal infection among pet macaques in Southeast Asia,
a region with a high prevalence of human yaws. This finding, along with studies
showing treponemal infection in nonhuman primates in Africa, should encourage a
One Health approach to yaws eradication and surveillance activities, possibly
including monitoring of nonhuman primates in yaws-endemic regions.
PMID- 28418298
TI - ESBL- and Carbapenemase-Producing Enterobacteriaceae in Patients with Bacteremia,
Yangon, Myanmar, 2014.
AB - Among 42 gram-negative bloodstream isolates from inpatients in 3 hospitals in
Yangon, Myanmar, admitted during July-December 2014, 16 (38%) were extended
spectrum beta-lactamase-producing Enterobacteriaceae and 6 (14%) produced
carbapenemase. The high prevalence of multidrug-resistant gram-negative bacteria
raises concerns about the empiric treatment of patients with sepsis in Yangon.
PMID- 28418299
TI - Control of Malaria Vector Mosquitoes by Insecticide-Treated Combinations of
Window Screens and Eave Baffles.
AB - We assessed window screens and eave baffles (WSEBs), which enable mosquitoes to
enter but not exit houses, as an alternative to indoor residual spraying (IRS)
for malaria vector control. WSEBs treated with water, the pyrethroid lambda
cyhalothrin, or the organophosphate pirimiphos-methyl, with and without a binding
agent for increasing insecticide persistence on netting, were compared with IRS
in experimental huts. Compared with IRS containing the same insecticide, WSEBs
killed similar proportions of Anopheles funestus mosquitoes that were resistant
to pyrethroids, carbamates and organochlorines and greater proportions of
pyrethroid-resistant, early exiting An. arabiensis mosquitoes. WSEBs with
pirimiphos-methyl killed greater proportions of both vectors than lambda
cyhalothrin or lambda-cyhalothrin plus pirimiphos-methyl and were equally
efficacious when combined with binding agent. WSEBs required far less insecticide
than IRS, and binding agents might enhance durability. WSEBs might enable
affordable deployment of insecticide combinations to mitigate against physiologic
insecticide resistance and improve control of behaviorally resistant, early
exiting vectors.
PMID- 28418300
TI - Population Responses during the Pandemic Phase of the Influenza A(H1N1)pdm09
Epidemic, Hong Kong, China.
AB - During August 2009-July 2010, we conducted 7 longitudinal telephone surveys among
503 adults in Hong Kong, China, to explore changes in their behavioral and
psychological responses to the influenza A(H1N1)pdm09 virus epidemic. Trends were
examined using generalized estimating equations models. Findings showed that
responses varied with the course of the pandemic.
PMID- 28418301
TI - Severe MRSA Enterocolitis Caused by a Strain Harboring Enterotoxins D, G, and I.
AB - We describe a case of methicillin-resistant Staphylococcus aureus (MRSA)
enterocolitis in a healthy adult with previous antibiotic exposure. Colonoscopy
revealed diffuse colitis and mild ileitis without ulceration. Stool cultures
demonstrated abundant growth of MRSA and absent normal flora. Oral vancomycin
treatment was effective and seems to be the consensus choice for therapy.
PMID- 28418302
TI - Anthrax Cases Associated with Animal-Hair Shaving Brushes.
AB - During the First World War, anthrax cases in the United States and England
increased greatly and seemed to be associated with use of new shaving brushes.
Further investigation revealed that the source material and origin of shaving
brushes had changed during the war. Cheap brushes of imported horsehair were
being made to look like the preferred badger-hair brushes. Unfortunately, some of
these brushes were not effectively disinfected and brought with them a nasty
stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data,
and case reports indicated that these cases originated from the use of
ineffectively disinfected animal-hair shaving brushes. This historical
information is relevant to current public health practice because renewed
interest in vintage and animal-hair shaving brushes has been seen in popular
culture. This information should help healthcare providers and public health
officials answer questions on this topic.
PMID- 28418303
TI - Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria
gonorrhoeae, Hawaii, USA.
AB - During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were
resistant to azithromycin; 5 had decreased in vitro susceptibility to
ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when
compared with local contemporary strains. Continued evolution and widespread
transmission of these strains might challenge the effectiveness of current
therapeutic options.
PMID- 28418304
TI - Meningococci of Serogroup X Clonal Complex 181 in Refugee Camps, Italy.
AB - Four cases of infection with serogroup X meningococci (MenX) (1 in 2015 and 3 in
2016) occurred in migrants living in refugee camps or reception centers in Italy.
All MenX isolates were identified as clonal complex 181. Our report suggests that
serogroup X represents an emerging health threat for persons arriving from
African countries.
PMID- 28418305
TI - Clinical Manifestations of Punta Toro Virus Species Complex Infections, Panama,
2009.
AB - An investigation in Panama found that Punta Toro virus species complex (PTVs) may
contribute to febrile illnesses with symptoms mirroring those of dengue fever.
However, further studies are needed to determine if PTV infection causes only a
mild disease or if it can have more serious manifestations in some patients.
PMID- 28418306
TI - Management of Bartonella Prosthetic Valve Endocarditis without Cardiac Surgery.
AB - Two cases of Bartonella prosthetic valve endocarditis were cured when treated for
2 weeks with gentamicin and 3 months with doxycycline. Clinical cure correlated
with decreased Bartonella antibody titers. This report suggests a strategy to
monitor, treat, and cure Bartonella prosthetic valve endocarditis.
PMID- 28418307
TI - Serogroup B Meningococcal Disease Vaccine Recommendations at a University, New
Jersey, USA, 2016.
AB - In response to a university-based serogroup B meningococcal disease outbreak, the
serogroup B meningococcal vaccine Trumenba was recommended for students, a rare
instance in which a specific vaccine brand was recommended. This outbreak
highlights the challenges of using molecular and immunologic data to inform real
time response.
PMID- 28418308
TI - Chromosomal 16S Ribosomal RNA Methyltransferase RmtE1 in Escherichia coli
Sequence Type 448.
AB - We identified rmtE1, an uncommon 16S ribosomal methyltransferase gene, in an
aminoglycoside- and cephalosporin-resistant Escherichia coli sequence type 448
clinical strain co-harboring blaCMY-2. Long-read sequencing revealed insertion of
a 101,257-bp fragment carrying both resistance genes to the chromosome. Our
findings underscore E. coli sequence type 448 as a potential high-risk multidrug
resistant clone.
PMID- 28418309
TI - Translation of Real-Time Infectious Disease Modeling into Routine Public Health
Practice.
AB - Infectious disease dynamic modeling can support outbreak emergency responses. We
conducted a workshop to canvas the needs of stakeholders in Australia for
practical, real-time modeling tools for infectious disease emergencies. The
workshop was attended by 29 participants who represented government, defense,
general practice, and academia stakeholders. We found that modeling is underused
in Australia and its potential is poorly understood by practitioners involved in
epidemic responses. The development of better modeling tools is desired. Ideal
modeling tools for operational use would be easy to use, clearly indicate
underlying parameterization and assumptions, and assist with policy and decision
making.
PMID- 28418311
TI - Reemergence of African Swine Fever in Zimbabwe, 2015.
AB - Zimbabwe is the only country in southern Africa with no reported African swine
fever (ASF) outbreaks during 1993-2014. However, the 2015 discovery of genotype
II ASF virus in Zimbabwe indicates the reemergence of ASF in this country and
suggests that this viral genotype may be spreading through eastern and southern
Africa.
PMID- 28418310
TI - Diagnosis and Management of Borrelia turicatae Infection in Febrile Soldier,
Texas, USA.
AB - In August 2015, a soldier returned from field exercises in Texas, USA, with
nonspecific febrile illness. Culture and sequencing of spirochetes from
peripheral blood diagnosed Borrelia turicatae infection. The patient recovered
after receiving doxycycline. No illness occurred in asymptomatic soldiers
potentially exposed to the vector tick and prophylactically given treatment.
PMID- 28418312
TI - Exposure Characteristics of Hantavirus Pulmonary Syndrome Patients, United
States, 1993-2015.
AB - Those at highest risk are persons in occupations with potential for rodent
exposure and American Indian women 40--64 years of age.
PMID- 28418313
TI - mcr-1 Colistin Resistance in ESBL-Producing Klebsiella pneumoniae, France.
AB - We report intestinal carriage of an extended-spectrum beta-lactamase-producing
Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L)
in a patient in France who had been hospitalized for fungal meningitis. The
strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are
associated with colistin resistance.
PMID- 28418314
TI - Population Genomics of Legionella longbeachae and Hidden Complexities of
Infection Source Attribution.
AB - Legionella longbeachae is the primary cause of legionellosis in Australasia and
Southeast Asia and an emerging pathogen in Europe and the United States; however,
our understanding of the population diversity of L. longbeachae from patient and
environmental sources is limited. We analyzed the genomes of 64 L. longbeachae
isolates, of which 29 were from a cluster of legionellosis cases linked to
commercial growing media in Scotland in 2013 and 35 were non-outbreak-associated
isolates from Scotland and other countries. We identified extensive genetic
diversity across the L. longbeachae species, associated with intraspecies and
interspecies gene flow, and a wide geographic distribution of closely related
genotypes. Of note, we observed a highly diverse pool of L. longbeachae genotypes
within compost samples that precluded the genetic establishment of an infection
source. These data represent a view of the genomic diversity of L. longbeachae
that will inform strategies for investigating future outbreaks.
PMID- 28418315
TI - Regional Transmission of Salmonella Paratyphi A, China, 1998-2012.
AB - To explore transmission patterns and genetic relationships of Salmonella enterica
serovar Paratyphi A in China, we conducted a genome-wide single-nucleotide
polymorphism analysis on the strains in the 4 provinces in which incidence was
highest during 1998-2012. Markedly phylogeographic clustering suggested regional
virus circulation after introduction from areas in southeastern China.
PMID- 28418316
TI - Amoxicillin and Ceftriaxone as Treatment Alternatives to Penicillin for Maternal
Syphilis.
AB - There is no proven alternative to penicillin for treatment of maternal syphilis.
We report 2 case-patients with maternal syphilis who were successfully treated
without penicillin. We used amoxicillin and probenecid for the first case-patient
and amoxicillin, probenecid, and ceftriaxone for the second case-patient.
PMID- 28418317
TI - No Such Thing as Chronic Q Fever.
AB - Modern diagnostic methods enable clinicians to look beyond a diagnosis of chronic
Q fever and discern whether patients instead have persistent focalized Coxiella
burnetii infection(s). Use of these methods and development of criteria to define
and treat such infections, especially cardiovascular infections, will improve the
prognosis for patients previously thought to have chronic Q fever.
PMID- 28418318
TI - Carbapenem-Resistant Enterobacter cloacae in Patients from the US Veterans Health
Administration, 2006-2015.
AB - We analyzed carbapenem-resistant Enterobacteriaceae (CRE) trends among patients
from the US Veterans Health Administration (VHA). After the emergence of CRE in
the eastern United States, resistance rates remained stable in Klebsiella
pneumoniae but increased in Enterobacter cloacae complex, suggesting a "second
epidemic". VHA offers a vantage point for monitoring nationwide CRE trends.
PMID- 28418319
TI - Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium.
AB - Escalating resistance to azithromycin and moxifloxacin is being reported for
Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we
found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA
(5%). ParC S83 changes were associated with moxifloxacin failure. Combined
macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for
which recommended therapies would be ineffective.
PMID- 28418320
TI - Antimicrobial Drug Resistance among Refugees from Syria, Jordan.
PMID- 28418322
TI - Binaural Interference: Quo Vadis?
AB - The reality of the phenomenon of binaural interference with speech recognition
has been debated for two decades. Research has taken one of two avenues; group
studies or case reports. In group studies, a sample of the elderly population is
tested on speech recognition under three conditions; binaural, monaural right and
monaural left. The aim is to determine the percent of the sample in which the
expected outcome (binaural score-better-than-either-monaural score) is reversed
(i.e., one of the monaural scores is better than the binaural score). This
outcome has been commonly used to define binaural interference. The object of
group studies is to answer the "how many" question, what is the prevalence of
binaural interference in the sample. In case reports the binaural interference
conclusion suggested by the speech recognition tests is not accepted until it has
been corroborated by other independent diagnostic audiological measures. The aim
is to attempt to determine the basis for the findings, to answer the "why"
question. This article is at once tutorial, editorial and a case report. We argue
that it is time to accept the reality of the phenomenon of binaural interference,
to eschew group statistical approaches in search of an answer to the "how many"
question, and to focus on individual case reports in search of an answer to the
"why" question.
PMID- 28418321
TI - S100A10 identified in a genome-wide gene * cannabis dependence interaction
analysis of risky sexual behaviours.
AB - BACKGROUND: We conducted a genome-wide gene * environment interaction analysis to
identify genetic variants that interact with cannabis dependence (CaD) in
influencing risky sexual behaviours (RSB). METHODS: Our sample included cannabis
exposed and sexually experienced African-American and European-American
participants. A DSM-IV CaD diagnosis and RSB were evaluated using the Semi
Structured Assessment for Drug Dependence and Alcoholism. We analyzed RSBs as a
score that takes into account experiences of unprotected sex and multiple sexual
partners. RESULTS: A total of 3350 people participated in our study; 43% had a
CaD diagnosis, 56% were African-American and 33% were women. We identified a
genome-wide significant locus in African-American participants (S100A10
rs72993629, p = 2.73 * 10-8) and a potential transpopulation signal in women
(CLTC rs12944716, p = 5.27 * 10-8). A resting-state fMRI follow-up analysis of
S100A10 rs72993629 conducted in an independent cohort showed 2 significant
associations: reduced power of the left paracentral lobule in amplitude of low
frequency fluctuations (ALFF) analysis (p = 7.8 * 10-3) and reduced power of the
right pallidum in fractional ALFF analysis (p = 4.6 * 10-3). The activity of
these brain regions is known to be involved in sexual functions and behaviours.
The S100A10 result functionally recapitulated our S100B finding observed in our
previous genome-wide association study of CaD. The probability of identifying 2
S100 genes in 2 independent genome-wide investigations by chance is approximately
1 in 1.1 million. LIMITATIONS: We were not able to identify any African-American
cohort with appropriate sample size, and phenotypic assessment is available to
replicate our findings. CONCLUSION: The S100A10 and S100B genes, which are
located on different chromosomes, encode specialized calcium-binding proteins.
These data support a role for calcium homeostasis in individuals with CaD and its
induced behaviours.
PMID- 28418323
TI - The Personality Profile of Tinnitus Sufferers and a Nontinnitus Control Group.
AB - BACKGROUND: Chronic tinnitus (phantom perception of sound) significantly disrupts
quality of life in 15-20% of those who experience it. Understanding how certain
personality traits impact tinnitus perception and distress can be beneficial for
the development of interventions to improve the lives of tinnitus sufferers.
PURPOSE: Four key self-reported personality traits (social closeness, stress
reaction, alienation, and self-control) were identified from previous research as
being associated with tinnitus. These were compared between tinnitus and age-,
gender-, and hearing level-matched nontinnitus controls to see whether underlying
profile differences exist, and if personality traits levels correlate with
various tinnitus characteristics assessed in typical clinical questionnaires.
RESEARCH DESIGN: A Web-based personality survey was administered comprising of
self-control, stress reaction, alienation, and social closeness subscale
questions of the Multidimensional Personality Questionnaire, the Hearing Handicap
Inventory-Screening Version, TFI, and the Tinnitus Case History Questionnaire.
STUDY SAMPLE: A total of 154 participants with tinnitus (81 males, 73 females,
mean age = 62.6 yr) and 61 control (32 males, 29 females, mean age = 59.62 yr)
participants were recruited via e-mail invitations to a tinnitus research clinic
database, poster, and social media Web site advertising. DATA COLLECTION AND
ANALYSIS: Statistical analysis was conducted using parametric statistics and IBM
SPSS(r) Version 22 software. RESULTS: Tinnitus sufferers displayed higher levels
of stress reaction, lower social closeness, lower self-control, and higher
alienation than the control group (p < 0.05). Alienation was related to tinnitus
pitch and self-reported hyperacusis measured using the Tinnitus Case History
Questionnaire (p < 0.05). Stress reaction correlated with self-reported
hyperacusis, whether tinnitus sufferers had sought other treatments, and whether
loud sounds make the tinnitus worse (p < 0.05). CONCLUSIONS: The four personality
traits examined in this study exhibited a consistent association with tinnitus
perception and distress, and differentiated tinnitus sufferers from nontinnitus
control. Some of the traits also correlated significantly with certain
characteristics measured in tinnitus history questionnaires. Personality traits
are described in relation to "maladaptive" residuals under the Adaptation Level
Theory model of tinnitus. The results of the study suggest that certain
personality traits correlate with the clinical presentation of tinnitus.
PMID- 28418324
TI - Prosody Perception and Production in Children with Hearing Loss and Age- and
Gender-Matched Controls.
AB - BACKGROUND: Auditory development in children with hearing loss, including the
perception of prosody, depends on having adequate input from cochlear implants
and/or hearing aids. Lack of adequate auditory stimulation can lead to delayed
speech and language development. Nevertheless, prosody perception and production
in people with hearing loss have received less attention than other aspects of
language. The perception of auditory information conveyed through prosody using
variations in the pitch, amplitude, and duration of speech is not usually
evaluated clinically. PURPOSE: This study (1) compared prosody perception and
production abilities in children with hearing loss and children with normal
hearing; and (2) investigated the effect of age, hearing level, and musicality on
prosody perception. RESEARCH DESIGN: Participants were 16 children with hearing
loss and 16 typically developing controls matched for age and gender. Fifteen of
the children with hearing loss were tested while using amplification (n = 9
hearing aids, n = 6 cochlear implants). Six receptive subtests of the Profiling
Elements of Prosody in Speech-Communication (PEPS-C), the Child Paralanguage
subtest of Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA 2), and Contour and
Interval subtests of the Montreal Battery of Evaluation of Amusia (MBEA) were
used. Audio recordings of the children's reading samples were rated using a
perceptual prosody rating scale by nine experienced listeners who were blinded to
the children's hearing status. STUDY SAMPLE: Thirty two children, 16 with hearing
loss (mean age = 8.71 yr) and 16 age- and gender-matched typically developing
children with normal hearing (mean age = 8.87 yr). DATA COLLECTION AND ANALYSIS:
Assessments were completed in one session lasting 1-2 hours in a quiet room. Test
items were presented using a laptop computer through loudspeaker at a comfortable
listening level. For children with hearing loss using hearing instruments, all
tests were completed with hearing devices set at their everyday listening
setting. RESULTS: All PEPS-C subtests and total scores were significantly lower
for children with hearing loss compared to controls (p < 0.05). The hearing loss
group performed more poorly than the control group in recognizing happy, sad, and
fearful emotions in the DANVA 2 subtest. Musicality (composite MBEA scores and
musical experience) was significantly correlated with prosody perception scores,
but this link was not evident in the regression analyses. Regression modeling
showed that age and hearing level (better ear pure-tone average) accounted for
55.4% and 56.7% of the variance in PEPS-C and DANVA 2 total scores, respectively.
There was greater variability for the ratings of pitch, pitch variation, and
overall impression of prosody in the hearing loss group compared to control
group. Prosody perception (PEPS-C and DANVA 2 total scores) and ratings of
prosody production were not correlated. CONCLUSIONS: Children with hearing loss
aged 7-12 yr had significant difficulties in understanding different aspects of
prosody and were rated as having more atypical prosody overall than controls.
These findings suggest that clinical assessment and speech-language therapy
services for children with hearing loss should be expanded to target prosodic
difficulties. Future studies should investigate whether musical training is
beneficial for improving receptive prosody skills.
PMID- 28418325
TI - Variation in Music Player Listening Level as a Function of Campus Location.
AB - BACKGROUND: There has been significant discussion in the literature regarding
music player use by adolescents and young adults, including whether device use is
driving an increase in hearing loss in these populations. While many studies
report relatively safe preferred listening levels, some studies with college
student participants have reported listening habits that may put individuals at
risk for noise-induced hearing loss (NIHL) if those listening habits continue
over the long term. PURPOSE: The goal of the current investigation was to extend
listening level data collection sites from urban city settings studied by others
to a more rural campus setting. RESEARCH DESIGN: This was a prospective study.
STUDY SAMPLE: Participants were 138 students on the University of Florida campus
(94 males, 44 females), 18 years or older (mean = 21 years; range: 18-33 years).
DATA COLLECTION AND ANALYSIS: In this investigation, the current output level
(listening level) was measured from personal listening devices used by students
as they passed by a recruiting table located in one of three areas of the
University of Florida campus. One location was in an open-air campus square; the
other two locations were outside the campus recreation building ("gym") and
outside the undergraduate library, with participants recruited as they exited the
gym or library buildings. After providing written informed consent, participants
completed a survey that included questions about demographics and typical
listening habits (hours per day, days per week). The output level on their device
was then measured using a "Jolene" mannequin. RESULTS: Average listening levels
for participants at the three locations were as follows: gym: 85.9 +/- 1.4 dBA;
campus square: 83.3 +/- 2.0 dBA; library: 76.9 +/- 1.3 dBA. After adjusting to
free-field equivalent level, average listening levels were gym: 79.7 +/- 1.4 dBA;
campus square: 76.9 +/- 2.1 dBA; library: 70.4 +/- 1.4 dBA. There were no
statistically significant differences between male and female listeners, and
there were no reliable differences as a function of race. After accounting for
daily and weekly use patterns, 5% were deemed at risk based on the criteria put
forward by the Occupational Safety and Health Administration, and 9% were deemed
at risk based on the guidance provided by the National Institute for Occupational
Safety and Health. CONCLUSIONS: Some 5-10% of the participants were deemed at
risk; this finding is consistent with other studies using similar methods. It is
possible that the same listeners would have selected different listening levels
in other noise backgrounds, however. This unknown variable makes it difficult to
estimate risk with a single listening level measurement.
PMID- 28418326
TI - Artifact in Pediatric Oculomotor Findings during Videonystagmography: A
Retrospective Analysis.
AB - BACKGROUND: Accurate measurement of oculomotor function using videonystagmography
(VNG) is imperative for diagnosis and management of patients with reported
dizziness. The oculomotor evaluation during VNG utilizes video-oculography
providing valuable information regarding the central structures and pathways that
control eye movements. Artifact may have an effect on the overall validity and
reliability of VNG oculomotor tracings and can result from patient and/or
recording errors. It is postulated that artifact could occur more frequently in
the pediatric population due to both patient and equipment factors. PURPOSE: The
purpose of this study was to systematically evaluate the occurrence and impact of
artifact on saccades, smooth pursuit, and optokinetic (OPK) testing in normal
pediatric and adult subjects using commercially available clinical VNG equipment
and standard clinical protocols for oculomotor testing. RESEARCH DESIGN: The
present study utilized a retrospective analysis of a repeated measures design.
STUDY SAMPLE: Oculomotor results from a total of 62 participants were analyzed.
Portions of these data have been presented in a previous research study. Group 1
consisted of twenty-nine 4- to 6-yr-olds with an average age of 4.86 (SD = 0.88)
yr. Group 2 consisted of thirty-three 22- to 44-yr-olds with an average age of
25.2 (SD = 5.34) yr. DATA COLLECTION AND ANALYSIS: Raw oculomotor recordings were
analyzed "offline" by a single masked, trained investigator. Each tracing was
evaluated for instances of artifact including eye blinks, eye closure, eyes
moving in opposite direction of the target, eye tracking software problems, and
overall poor morphology. The number of instances of artifact were noted and
recorded for each participant in both groups. Individual eye movements not
affected by artifact were included for final analysis. Artifact rejection
techniques were also compared. RESULTS: The results indicated increased artifact
for the pediatric group for saccade and smooth pursuit testing. Additionally, a
significant decrease in instances of artifact was noted with an increase in age
in months for both saccade and smooth pursuit findings. OPK results did not
indicate any significant difference in instances of artifact between the
pediatric and adult groups or any decrease in instances of artifact with
increasing age in the pediatric group. Artifact rejection technique did not have
a significant effect on oculomotor measures for either age group. CONCLUSIONS:
Pediatric patients exhibit increased instances of artifact during VNG oculomotor
testing, specifically during saccade and smooth pursuit testing, at least for the
4- to 6-yr-old population. A general age effect was also noted in this age group,
with decreased artifact noted with increasing age. Artifact rejection technique
was not a significant factor suggesting standard compared based strategies may be
sufficient for use in the pediatric population. Additional study into the effect
of artifact on oculomotor results for infants to age 3 yr and ages 7- to 18-yr
old, in the disordered population, and with additional equipment manufacturers is
needed to confirm these results and further describe the impact of artifact on
oculomotor findings in the pediatric population.
PMID- 28418327
TI - Auditory and Cognitive Factors Associated with Speech-in-Noise Complaints
following Mild Traumatic Brain Injury.
AB - BACKGROUND: Auditory complaints following mild traumatic brain injury (MTBI) are
common, but few studies have addressed the role of auditory temporal processing
in speech recognition complaints. PURPOSE: In this study, deficits understanding
speech in a background of speech noise following MTBI were evaluated with the
goal of comparing the relative contributions of auditory and nonauditory factors.
RESEARCH DESIGN: A matched-groups design was used in which a group of listeners
with a history of MTBI were compared to a group matched in age and pure-tone
thresholds, as well as a control group of young listeners with normal hearing
(YNH). STUDY SAMPLE: Of the 33 listeners who participated in the study, 13 were
included in the MTBI group (mean age = 46.7 yr), 11 in the Matched group (mean
age = 49 yr), and 9 in the YNH group (mean age = 20.8 yr). DATA COLLECTION AND
ANALYSIS: Speech-in-noise deficits were evaluated using subjective measures as
well as monaural word (Words-in-Noise test) and sentence (Quick Speech-in-Noise
test) tasks, and a binaural spatial release task. Performance on these measures
was compared to psychophysical tasks that evaluate monaural and binaural temporal
fine-structure tasks and spectral resolution. Cognitive measures of attention,
processing speed, and working memory were evaluated as possible causes of
differences between MTBI and Matched groups that might contribute to speech-in
noise perception deficits. RESULTS: A high proportion of listeners in the MTBI
group reported difficulty understanding speech in noise (84%) compared to the
Matched group (9.1%), and listeners who reported difficulty were more likely to
have abnormal results on objective measures of speech in noise. No significant
group differences were found between the MTBI and Matched listeners on any of the
measures reported, but the number of abnormal tests differed across groups.
Regression analysis revealed that a combination of auditory and auditory
processing factors contributed to monaural speech-in-noise scores, but the
benefit of spatial separation was related to a combination of working memory and
peripheral auditory factors across all listeners in the study. CONCLUSIONS: The
results of this study are consistent with previous findings that a subset of
listeners with MTBI has objective auditory deficits. Speech-in-noise performance
was related to a combination of auditory and nonauditory factors, confirming the
important role of audiology in MTBI rehabilitation. Further research is needed to
evaluate the prevalence and causal relationship of auditory deficits following
MTBI.
PMID- 28418328
TI - Internet-Based Intervention for Tinnitus: Outcome of a Single-Group Open Trial.
AB - BACKGROUND: Managing chronic tinnitus is challenging, and innovative ways to
address the resulting health-care burden are required. Internet-based cognitive
behavioral therapy (iCBT) for tinnitus shows promise as a cost-effective
treatment option. The feasibility and effectiveness of iCBT in the United Kingdom
are yet to be explored. Furthermore, it is not known if iCBT can be supported by
an audiologist rather than a psychologist. PURPOSE: This study aimed to determine
the feasibility of guided iCBT using audiological support on tinnitus distress
and tinnitus-related comorbidities. Furthermore, it aimed to establish the
feasibility of iCBT for tinnitus distress in the United Kingdom, by determining
recruitment, attrition, and compliance rates. Finally, it aimed to identify which
aspects of the protocol require refinement for subsequent clinical trials.
RESEARCH DESIGN: A single-group open trial design was implemented. This study
would serve as a prerequisite study, to identify barriers, before undertaking
effectiveness trials. STUDY SAMPLE: Participants consisted of 37 adults (18
males, 19 females), with an age range of between 50 and 59 yr. The mean
preintervention tinnitus severity rating was 56.15 (standard deviation = 18.35),
which is categorized as "severe tinnitus" as measured by the Tinnitus Functional
Index (TFI). Five participants withdrew during the study, and 29 of the remaining
participants completed the postintervention questionnaire. INTERVENTION: The
guided iCBT intervention ran over an eight-week period and consisted of 16
obligatory modules and five optional modules. The intervention was designed to be
interactive, interesting, and stimulating. A key element was the provision of
support from an audiologist throughout the program. DATA COLLECTION AND ANALYSIS:
Online questionnaires were used throughout the study. These were administered at
baseline and postintervention to determine attrition and compliance rates and to
facilitate sample size estimates for further clinical trials. Outcome measures
for tinnitus severity, hearing handicap, insomnia, cognitive functioning,
hyperacusis, anxiety, depression, and life satisfaction were used to investigate
the effects of iCBT with audiological support. In addition, a weekly
questionnaire was incorporated to monitor change in tinnitus distress while
undertaking the intervention. RESULTS: Feasibility was established using an
audiologist to support this guided iCBT intervention, as a significant change
postintervention was found for tinnitus severity, as measured by the TFI and the
Tinnitus Handicap Inventory, Screening version. The attrition rate was 22% and
compliance was variable. Although these results were based on a small sample,
they provide encouraging evidence for the feasibility of delivering iCBT
treatment for tinnitus symptoms with audiology support in the United Kingdom.
CONCLUSIONS: An Internet-based intervention of tinnitus appears to be feasible in
the United Kingdom when using audiological support. Randomized controlled trials
to further investigate the effectiveness of iCBT for tinnitus in the United
Kingdom are required.
PMID- 28418329
TI - Phoneme Error Pattern by Heritage Speakers of Spanish on an English Word
Recognition Test.
AB - BACKGROUND: Heritage speakers acquire their native language from home use in
their early childhood. As the native language is typically a minority language in
the society, these individuals receive their formal education in the majority
language and eventually develop greater competency with the majority than their
native language. To date, there have not been specific research attempts to
understand word recognition by heritage speakers. It is not clear if and to what
degree we may infer from evidence based on bilingual listeners in general.
PURPOSE: This preliminary study investigated how heritage speakers of Spanish
perform on an English word recognition test and analyzed their phoneme errors.
RESEARCH DESIGN: A prospective, cross-sectional, observational design was
employed. STUDY SAMPLE: Twelve normal-hearing adult Spanish heritage speakers
(four men, eight women, 20-38 yr old) participated in the study. Their language
background was obtained through the Language Experience and Proficiency
Questionnaire. Nine English monolingual listeners (three men, six women, 20-41 yr
old) were also included for comparison purposes. DATA COLLECTION AND ANALYSIS:
Listeners were presented with 200 Northwestern University Auditory Test No. 6
words in quiet. They repeated each word orally and in writing. Their responses
were scored by word, word-initial consonant, vowel, and word-final consonant.
Performance was compared between groups with Student's t test or analysis of
variance. Group-specific error patterns were primarily descriptive, but
intergroup comparisons were made using 95% or 99% confidence intervals for
proportional data. RESULTS: The two groups of listeners yielded comparable scores
when their responses were examined by word, vowel, and final consonant. However,
heritage speakers of Spanish misidentified significantly more word-initial
consonants and had significantly more difficulty with initial /p, b, h/ than
their monolingual peers. The two groups yielded similar patterns for vowel and
word-final consonants, but heritage speakers made significantly fewer errors with
/e/ and more errors with word-final /p, k/. CONCLUSIONS: Data reported in the
present study lead to a twofold conclusion. On the one hand, normal-hearing
heritage speakers of Spanish may misidentify English phonemes in patterns
different from those of English monolingual listeners. Not all phoneme errors can
be readily understood by comparing Spanish and English phonology, suggesting that
Spanish heritage speakers differ in performance from other Spanish-English
bilingual listeners. On the other hand, the absolute number of errors and the
error pattern of most phonemes were comparable between English monolingual
listeners and Spanish heritage speakers, suggesting that audiologists may assess
word recognition in quiet in the same way for these two groups of listeners, if
diagnosis is based on words, not phonemes.
PMID- 28418332
TI - Sequential sensory and decision processing in posterior parietal cortex.
AB - Decisions about the behavioral significance of sensory stimuli often require
comparing sensory inference of what we are looking at to internal models of what
we are looking for. Here, we test how neuronal selectivity for visual features is
transformed into decision-related signals in posterior parietal cortex (area
LIP). Monkeys performed a visual matching task that required them to detect
target stimuli composed of conjunctions of color and motion-direction. Neuronal
recordings from area LIP revealed two main findings. First, the sequential
processing of visual features and the selection of target-stimuli suggest that
LIP is involved in transforming sensory information into decision-related
signals. Second, the patterns of color and motion selectivity and their impact on
decision-related encoding suggest that LIP plays a role in detecting target
stimuli by comparing bottom-up sensory inputs (what the monkeys were looking at)
and top-down cognitive encoding inputs (what the monkeys were looking for).
PMID- 28418331
TI - Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues.
AB - The role of the cellular microenvironment in enabling metazoan tissue genesis
remains obscure. Ctenophora has recently emerged as one of the earliest-branching
extant animal phyla, providing a unique opportunity to explore the evolutionary
role of the cellular microenvironment in tissue genesis. Here, we characterized
the extracellular matrix (ECM), with a focus on collagen IV and its variant,
spongin short-chain collagens, of non-bilaterian animal phyla. We identified
basement membrane (BM) and collagen IV in Ctenophora, and show that the
structural and genomic features of collagen IV are homologous to those of non
bilaterian animal phyla and Bilateria. Yet, ctenophore features are more diverse
and distinct, expressing up to twenty genes compared to six in vertebrates.
Moreover, collagen IV is absent in unicellular sister-groups. Collectively, we
conclude that collagen IV and its variant, spongin, are primordial components of
the extracellular microenvironment, and as a component of BM, collagen IV enabled
the assembly of a fundamental architectural unit for multicellular tissue
genesis.
PMID- 28418333
TI - Nonlinear feedback drives homeostatic plasticity in H2O2 stress response.
AB - Homeostatic systems that rely on genetic regulatory networks are intrinsically
limited by the transcriptional response time, which may restrict a cell's ability
to adapt to unanticipated environmental challenges. To bypass this limitation,
cells have evolved mechanisms whereby exposure to mild stress increases their
resistance to subsequent threats. However, the mechanisms responsible for such
adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and
microfluidics to investigate the adaptive response of budding yeast to temporally
controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is
a systems-level property resulting from nonlinearity of H2O2 scavenging by
peroxiredoxins and our study reveals that this regulatory scheme induces a
striking hormetic effect of extracellular H2O2 stress on replicative longevity.
Our study thus provides a novel quantitative framework bridging the molecular
architecture of a cellular homeostatic system to the emergence of nonintuitive
adaptive properties.
PMID- 28418334
TI - Juvenile Idiopathic Arthritis.
AB - Juvenile idiopathic arthritis is the most common chronic rheumatic disease of
unknown aetiology in childhood and predominantly presents with peripheral
arthritis. The disease is divided into several subgroups, according to
demographic characteristics, clinical features, treatment modalities and disease
prognosis. Systemic juvenile idiopathic arthritis, which is one of the most
frequent disease subtypes, is characterized by recurrent fever and rash.
Oligoarticular juvenile idiopathic arthritis, common among young female patients,
is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis.
Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult
rheumatoid arthritis, is seen in less than 10% of paediatric patients.
Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific
for childhood, appears with widespread large- and small-joint involvement.
Enthesitis-related arthritis is a separate disease subtype, characterized by
enthesitis and asymmetric lower-extremity arthritis. This disease subtype
represents the childhood form of adult spondyloarthropathies, with human
leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton
involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash,
accompanied by arthritis, nail pitting and dactylitis. Disease complications can
vary from growth retardation and osteoporosis secondary to treatment and disease
activity, to life-threatening macrophage activation syndrome with multi-organ
insufficiency. With the advent of new therapeutics over the past 15 years, there
has been a marked improvement in juvenile idiopathic arthritis treatment and long
term outcome, without any sequelae. The treatment of juvenile idiopathic
arthritis patients involves teamwork, including an experienced paediatric
rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist
and a physiotherapist. The primary goals of treatment are to eliminate active
disease, to normalize joint function, to preserve normal growth and to prevent
long-term joint damage. Timely and aggressive treatment is important to provide
early disease control. The first-line treatment includes disease-modifying anti
rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with
corticosteroids, used in different dosages and routes (oral, intravenous, intra
articular). Intra-articular application of steroids seems to be an effective
treatment modality, especially in monoarthritis. Biological agents should be
added in the treatment of unresponsive patients. Anti-tumour necrosis factor
agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra,
canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory
agents (abatacept) have been shown to be safe and effective in childhood
patients. Recent studies reported sustained reduction in joint damage with even
complete clinical improvement in paediatric patients, compared to previous data.
PMID- 28418335
TI - Evaluation of Dynamic Disulphide/Thiol Homeostasis in Silica Exposed Workers.
AB - BACKGROUND: Oxidative stress is implicated as one of the main molecular mechanism
underlying silicosis. AIMS: In this study, our aim was to asses the redox status
in occupationally silica-exposed workers, by evaluating the dynamic thiol
disulphide homeostasis. STUDY DESIGN: Case-control study. METHODS: Thirty-six
male workers occupationally exposed to silica particles and 30 healthy
volunteers, working as office workers were included to the study. Posteroanterior
chest radiographs and pulmonary function tests of both groups were evaluated.
Also serum thiol disulphide levels were measured using the spectrophotometric
method described by Erel and Neselioglu. RESULTS: Among the 36 workers that
underwent pulmonary function tests 6 (17%) had obstructive, 7 (19%) had
restrictive, 6 (17%) had obstructive and restrictive signs whereas 17 (47%) had
no signs. The mean PFTs results of silica-exposed workers were significantly
lower than control subjects. The serum disulphide levels of silica-exposed
workers were significantly higher than control subjects (23.84+/-5.89 MUmol/L and
21.18+/-3.44 MUmol/L, respectively p=0.02). CONCLUSION: The serum disulphide
levels, a biomarker of oxidative stress, are found to be higher in silica-exposed
workers.
PMID- 28418336
TI - Intracranial Lesions in Children and Adolescents with Morbid Obesity.
AB - BACKGROUND: Intracranial lesions may affect the hypothalamo-hypophyseal axis and
lead to some neuro-endocrinological dysfunctions (hyperphagia, sleep disorders
and hormonal dysfunctions). There is a very limited number of studies about
childhood obesity and intracranial lesions. AIMS: To evaluate the incidence of
intracranial lesions and its role in clinical symptoms and aetiology in cases
with morbid obesity who have been admitted to the paediatric endocrinology
department with this complaint. STUDY DESIGN: Cross-sectional study. METHODS: A
total of 120 cases admitted to the paediatric endocrinology department with the
complaint of morbid obesity between 2002 and 2015 were included in this study. A
detailed history was taken and a physical examination was performed; biochemical,
hormonal parameters were evaluated. Contrast dynamic magnetic resonance imaging
was performed in order to visualize cranial pathologies. RESULTS: An intracranial
lesions was detected in 16.6% of the patients and 55% of these lesions were
adenoma of the hypophysis. Prolactin levels were increased in six patients but
front hypophyseal hormone levels were within normal range in the rest of the
patients. Growth velocity of the patients was not affected. CONCLUSION: In our
study, the incidence of intracranial lesions in children and adolescents with
morbid obesity was much higher than in the normal population. According to this
data, we are of the opinion that contrast dynamic magnetic resonance imaging is
helpful in children with morbid obesity for the early detection of the mass
before it causes any clinical or neurological symptoms and in the prevention of
future complications.
PMID- 28418337
TI - A Simple Measure to Assess Hyperinflation and Air Trapping: 1-Forced Expiratory
Volume in Three Second / Forced Vital Capacity.
AB - BACKGROUND: Several recent studies have suggested that 1 minus-forced expiratory
volume expired in 3 seconds / forced vital capacity (1-FEV3/FVC) may be an
indicator of distal airway obstruction and a promising measure to evaluate small
airways dysfunction. AIMS: To investigate the associations of 1-FEV3/FVC with the
spirometric measures and lung volumes that assess small airways dysfunction and
reflects hyperinflation and air trapping. STUDY DESIGN: Retrospective cross
sectional study. METHODS: Retrospective assessment of a total of 1110 cases who
underwent body plethysmographic lung volume estimations between a time span from
2005 to 2012. Patients were assigned into two groups: firstly by FEV1/FVC
(FEV1/FVC <70% vs. FEV1/FVC >=70%); secondly by FEV3/FVC < lower limits of normal
(LLN) (FEV3/FVC < LLN vs. FEV3/FVC >= LLN). Spirometric indices and lung volumes
measured by whole-body plethysmography were compared in groups. Also the
correlation of spirometric indices with measured lung volumes were assessed in
the whole-study population and in subgroups stratified according to FEV1/FVC and
FEV3/FVC. RESULTS: Six hundred seven (54.7%) were male and 503 (45.3%) were
female, with a mean age of 52.5+/-15.6 years. Mean FEV3/FVC and 1-FEV3/FVC were
87.05%, 12.95%, respectively. The mean 1-FEV3/FVC was 4.9% in the FEV1/FVC >=70%
group (n=644) vs. 24.1% in the FEV1/FVC <70% group (n=466). A positive
correlation was found between 1-FEV3/FVC and residual volume (r=0.70; p<0.0001),
functional residual capacity-pleth (r=0.61; p<0.0001), and total lung capacity
(r=0.47; p<0.0001). 1-FEV3/FVC was negatively correlated with forced expiratory
flow25-75 (r=-0.84; p<0.0001). The upper limit of 95% confidence interval for 1
FEV3/FVC was 13.7%. 1-FEV3/FVC showed significant correlations with parameters of
air trapping and hyperinflation measured by whole-body plethysmography.
Importantly, these correlations were higher in study participants with FEV1/FVC
<70% or FEV3/FVC < LLN compared to those with FEV1/FVC >=70% or FEV3/FVC >= LLN,
respectively. CONCLUSION: 1-FEV3/FVC can be easily calculated from routine
spirometric measurements. 1-FEV3/FVC is a promising marker of air trapping and
hyperinflation. We suggest that 1-FEV3/FVC is complementary to FEV1/FVC and
recommend clinicians to routinely report and evaluate together with FEV1/FVC
during spirometry.
PMID- 28418338
TI - Diagnosis of Nipple Discharge: Value of Magnetic Resonance Imaging and
Ultrasonography in Comparison with Ductoscopy.
AB - BACKGROUND: Pathologic nipple discharge, which is a common reason for referral to
the breast imaging service, refers to spontaneous or bloody nipple discharge that
arises from a single duct. The most common cause of nipple discharge is benign
breast lesions, such as solitary intraductal papilloma and papillomatosis.
Nevertheless, in rare cases, a malignant cause of nipple discharge can be found.
AIMS: To study the diagnostic value of ultrasonography, magnetic resonance
imaging, and ductoscopy in patients with pathologic nipple discharge, compare
their efficacy, and investigate the importance of magnetic resonance imaging in
the diagnosis of intraductal pathologies. STUDY DESIGN: Diagnostic accuracy
study. METHODS: Fifty patients with pathologic nipple discharge were evaluated by
ultrasonography and magnetic resonance imaging. Of these, 44 ductoscopic
investigations were made. The patients were classified according to magnetic
resonance imaging, ultrasonography, and ductoscopy findings. A total of 25
patients, whose findings were reported as intraductal masses, underwent surgery
oincluding endoscopic excision for two endoscopic excision. Findings were
compared with the pathology results that were accepted as the gold standard in
the description of the aetiology of nipple discharge. In addition, magnetic
resonance imaging, ultrasonography and ductoscopy findings were analysed
comparatively in patients who had no surgery. RESULTS: Intraductal masses were
reported in 26 patients, 20 of whom operated and established accurate diagnosis
of 18 patients on magnetic resonance imaging. According to the ultrasonography,
intraductal masses were identified in 22 patients, 17 of whom underwent surgery.
Ultrasonography established accurate diagnoses in 15 patients. Intraductal mass
was identified in 22 patients and ductoscopy established accurate diagnoses based
on histopathologic results in 16 patients. The sensitivities of methods were 75%
in ultrasonography, 90% in magnetic resonance imaging, and 94.6% in ductoscopy.
The specificities were 66.7% in ultrasonography, 66.7% in magnetic resonance
imaging, and 40% in ductoscopy. Intraductal papillomas were mostly observed as
oval nodules with well-circumscribed smooth margins within dilated ducts and
persistant in the dynamic analysis. Lesions that protruded into the lumen of the
ducts, either solitary or multiple, were characteristic ductoscopy findings of
our patients who were diagnosed as having papilloma/papillomatosis. CONCLUSION:
Magnetic resonance imaging and ductoscopy had no statistical superiority over
each other, however they were superior to ultrasonography in the diagnosis of
pathologic nipple discharge. Magnetic resonance imaging may be highly sensitive
for diagnosing nipple discharge with new techniques and sequences and a non
invasive method that more advantageous for showing ductal tree visualization and
is able to detect completely obstructed intraductal lesions.
PMID- 28418339
TI - Fetal Nasal Bone Length as a Novel Marker for Prediction of Adverse Perinatal
Outcomes in the First-Trimester of Pregnancy.
AB - BACKGROUND: Adverse outcomes of pregnancy are a challenging health-care problem.
Prediction of adverse pregnancy outcomes is important to prevent the morbidities
of the foetus and the mother. AIMS: To study the clinical interest of fetal nasal
bone length in predicting adverse pregnancy outcomes in the first trimester of
pregnancy. STUDY DESIGN: A population-based retrospective cohort study. METHODS:
Data from 868 women with first-trimester fetal nasal bone length and birth
records available were enrolled. Fetal nasal bone length percentiles were
determined and evaluated for their ability to predict adverse pregnancy outcomes
such as preterm birth, preterm labour, preterm premature rupture of membranes,
early preterm birth, gestational diabetes mellitus, gestational hypertension
preeclampsia, small-for-gestational age foetuses, macrosomia, oligohydramnios,
polyhydramnios and fetal distress. RESULTS: Fetal nasal bone length >95th
percentile was significantly associated with preterm labor and preterm premature
rupture of membranes (p=0.02, accuracy 0.91 and p=0.001, accuracy 0.94,
respectively), whereas nasal bone length >99th percentile was significantly
associated with preterm labor and oligohydramnios (p=0.006, accuracy 0.95 and
p=0.014, accuracy 0.97). CONCLUSION: Fetal nasal bone length at high percentiles
in the first trimester of pregnancy may aid in the prediction of adverse outcomes
such as preterm labour, preterm premature rupture of membranes and
oligohydramnios.
PMID- 28418340
TI - Risk Adapted Management of Febrile Neutrepenia and Early Cessation of Empirical
Antibiotherapy in Hematopoietic Stem Cell Transplantation Setting.
AB - BACKGROUND: Haematopoietic stem cell transplantation is a curative treatment
option for many haematological disorders. Infection following haematopoietic stem
cell transplantation is one of the major causes of mortality. AIMS: To
investigate the outcomes of early cessation of empirical antibiotic treatment per
protocol in febrile neutropenia patients who have undergone haematopoietic stem
cell transplantation at our clinic. STUDY DESIGN: Descriptive study. METHODS: The
present study retrospectively evaluated febrile neutropenia attacks in
haematopoietic stem cell transplantation recipients during the period June 2014 -
January 2015 at our haematopoietic stem cell transplantation clinic. RESULTS: A
total of 72 febrile neutropenia attacks were evaluated in 53 patients. In 46
febrile neutropenia attacks, microbiologic cultures revealed positive results. In
culture-positive febrile neutropenia episodes a single bacterium was isolated in
32 cases and multiple strains were isolated in 14. In 15 patients, empirical
antibiotic therapy was discontinued after 72 hours. These patients were
clinically stable, without evident focus of infection and had negative culture
results. Only 4 recurrent episodes were observed (27%) after cessation of
antibiotherapy. No patient died as a result of recurrent infection. The 30-day
and 100-day post-transplantation mortality rates of patients with febrile
neutropenia episodes were 11.3% (6/53) and 3.8% (2/53), respectively. Infection
related 30-day and 100-day mortality rates were 7.5% (4/53) and 0% (0/53),
respectively. CONCLUSION: The main message of our study is that early cessation
of empirical antibiotherapy seems to be feasible in eligible patients without
increasing febrile neutropenia mortality rates.
PMID- 28418341
TI - The Knowledge Level and Opinions of Physicians about the Medical and Legal
Procedures Related to Physical Child Abuse.
AB - BACKGROUND: In order to diagnose child abuse, physicians need to consider the
possibility of abuse in every child they encounter, have sufficient information
about the topic and manage the cases according to current law. AIMS: To determine
the knowledge level of physicians on child abuse and to learn their opinions
about the procedures when they suspect child abuse. STUDY DESIGN: A questionnaire
(cross-sectional) study. METHODS: A detailed questionnaire was applied to 390
physicians of whom 233 were general practitioners. The first part of the
questionnaire included demographic variables (age, gender, occupational
experience) and the frequency of child physical abuse cases encountered, since
that is the most easily diagnosed and proven form of abuse. The second part
consisted of 32 questions about diagnosis of physical child abuse and procedures
during the follow-up of the cases. Statistical analyses were performed using SPSS
version 18.0. RESULTS: Of the participating physicians, 47.4% (n=185) were female
and only 13.1% of the physicians had some kind of postgraduate training on child
abuse. The correct response rate of specialists compared to general practitioners
was significantly higher. A total of 263 (72.3%) physicians thought that there
was a specific law on physical child abuse in the Turkish Republic. More than two
thirds of physicians thought that reporting should only be addressed to Social
Services and physicians should not be obliged to report to law enforcement.
CONCLUSION: The results of the present study adds to the already known necessity
for better training of physicians about physical child abuse and the need to
refresh their knowledge through postgraduate courses. According to current
regulations, it is obligatory to report abuse cases to the public prosecutor
and/or police, therefore physicians also need training in respect of the legal
status and medico-legal approach to these cases.
PMID- 28418342
TI - Transsexual Mastectomy: Selection of Appropriate Technique According to Breast
Characteristics.
AB - BACKGROUND: Subcutaneous mastectomy for female- to-male transsexuals is usually
the first surgical pro- cedure in sexual reassignment. The main objective of
subcutaneous mastectomy is to create an aesthetically pleasing male chest contour
by removing all glandular tissue while minimizing chest wall scars. AIMS: In this
paper, we present our experience with subcutaneous mastectomy performed in female
to- male transsexual patients. The authors recommend their point of view to aid
in selecting the most suitable subcutaneous mastectomy technique depending on
breast characteristics. STUDY DESIGN: Retrospective cross-sectional study.
METHODS: Between March 2011 and December 2014, 52 patients underwent bilateral
subcutaneous mastec- tomies (total of 104 mastectomies), performed using the
following four techniques: Webster semicircular, concentric circular, vertical,
and apron flap. The tech- nique decision depended on the breast size, degree of
skin excess, skin elasticity, chest width, nipple areolar complex size and
position. RESULTS: Seventeen patients (32.7%) were operated with Webster
semicircular, 7 patients (13.5%) with con- centric periareolar, 12 patients with
vertical (23%); and 16 patients (30.8%) with the apron flap technique. The
overall postoperative complication rate was 13.4%. All patients were satisfied
with the aesthetic results of their subcutaneous mastectomies within the follow
up period. CONCLUSION: To obtain higher patient satisfaction with aesthetic
results and lower postoperative complication rates, breast characteristics are
evaluated in a detailed fashion, while choosing the ideal technique of Female-to
Male (FtM) subcutaneous mastectomy. The presented surgical new algorithm
facilitates the selection of the most reliable surgical technique.
PMID- 28418343
TI - The Use of Human Epididymis 4 and Cancer Antigen 125 Tumor Markers in the Benign
or Malignant Differential Diagnosis of Pelvic or Adnexal Masses.
AB - BACKGROUND: Ovarian cancer is one of the highest mortality cancers in
gynaecology. Discrimination of benign masses from malignant ones may sometimes
become a challenge for the clinician since there is not a reliable tumour marker,
thus some unnecessary, highly morbid operations can be performed. AIMS: To
explore the efficacy of human epididymis 4 (HE 4) and cancer antigen 125 (CA 125)
markers in differentiating malignant and benign pelvic masses of ovarian origin
and to identify the cut-off points for those markers. STUDY DESIGN: Prospective
study. METHODS: Fifty-one patients who were diagnosed and planned to undergo
surgery for ovarian mass between June 2008 and December 2008 were enrolled into
this study. Preoperative venous blood samples were taken and frozen for marker
investigation and final diagnoses were concluded by histopathological
examination. After recruitment of all cases CA 125 and HE 4 levels were
evaluated. RESULTS: The statistical analysis did not indicate any statistically
significant difference between the CA 125 levels of the patients with malignant
and benign adnexal masses (p=0.105). The HE 4 levels of the patients with
malignant adnexal masses were higher at a statistically significant level
compared to the patients with benign adnexal masses (p=0.002). For HE 4 tumour
marker and at the cut-off point of >25 pM, sensitivity was 1, specificity 0.40,
positive cut-off value 0.19, negative cut-off value 1, accuracy 0.47 and positive
likelihood ratio 1.65. CONCLUSION: Human epididymis 4 is a better diagnostic tool
than CA 125 in benign-malignant discrimination of adnexal masses. The cut-off
value of 25 pmol/L for human epididymis 4 will contribute to providing proper
guidance to patients with adnexal masses and applying the proper treatment
method.
PMID- 28418344
TI - Rare Giant Angiokeratoma of the Vulva: A Case Report.
AB - BACKGROUND: Angiokeratoma of fordyce occurring over on the vulva is a rare
condition. Fordyce angiokeratoma is observed more frequently among men than
women. In women, it is generally observed in later life, and appears as multiple
dark purple papules, measuring 2-4 mm, on the vulva. CASE REPORT: We present the
case of a 17-year-old white teenage girl with giant Fordyce angiokeratoma on the
right vulva. The angiokeratoma was removed and a V-Y advancement flap was made.
CONCLUSION: In the literature, this is the first childhood case reported in which
a reconstruction of the vulva was performed.
PMID- 28418345
TI - Cricotracheal Resection in a Patient with Severe Subglottic Stenosis - Advantages
of a Temporary Non-Cannulated Tracheostomy.
AB - BACKGROUND: Stenosis in the area of the cricotracheal segment is still a
challenging problem to be dealt with. Post-intubational cases mark an increase in
recent years due to the advances in intensive care, thoracic surgery and
neurosurgery departments. CASE REPORT: This paper describes a case report of a
patient with severe subglottic stenosis (grade III according to the Cotton-Myer
scale), introduces a new option in cricotracheal resections - postoperative
temporary non-cannulated tracheostomy and describes its advantages. CONCLUSION:
This variation of classical operative techniques provides additional fixation of
the trachea, thus relieving any transitory tension on the anastomosis; acts as a
valve and decreases the air-pressure in the upper airways during coughing and
sneezing in the post-operative period; and is an easy access point for video
tracheoscopy of the anastomosis.
PMID- 28418346
TI - Extra-Gastrointestinal Stromal Tumor of Prostate.
AB - BACKGROUND: Extra-gastrointestinal stromal tumor is defined as a mesenchymal
neoplasm arising from soft tissues outside the gastrointestinal tract. Prostatic
extra-gastrointestinal stromal tumor has rarely been noted. CASE REPORT: A 56
year-old man presented with pain in the anal region. A digital rectal examination
revealed that the prostate was markedly enlarged with a smooth, bulging surface.
Computerized tomography images showed a 6 cm heterogeneous, infiltrative tumor
within the prostate gland extending to the trigon of the bladder, left seminal
vesicle and rectum. The tru-cut biopsy of the prostate was reported as leiomyoma.
It was decided to perform surgery and the masses were easily and completely
removed from the adjacent structures. The case was reported as extra
gastrointestinal stromal tumor within the intermediate- risk category with free
surgical margins. Four years after the surgery, a locoregional failure was
observed and treated with imatinib. CONCLUSION: Stromal tumor, although rare,
should be considered in the differential diagnosis in patients with an enlarged
prostate.
PMID- 28418347
TI - Difficult Cases of Odontogenic Deep Neck Infections: A Report of Three Patients.
AB - BACKGROUND: Deep neck infections are important otolaryngologic emergencies due to
serious complications and the risk of airway compromise, which can lead to
mortality. Although the most common causes among pediatric patients are
tonsillitis and pharyngeal infections, odontogenic infections are an important
cause in adults. CASE REPORT: We present three patients with multiple deep neck
space abscess formation due to odontogenic infection. Two of them required
tracheotomy due to airway compromise, and one had mediastinitis. CONCLUSION: An
underestimated tooth infection can cause hazardous complications such as
mediastinitis and respiratory distress requiring tracheotomy.
PMID- 28418348
TI - Para Phimosis Leading to Glans Gangrene - A Devastating Preventable Complication.
PMID- 28418349
TI - Retrograde Gastric Intussusception.
PMID- 28418350
TI - Femoral Adamantinoma: A Rare Lesion in an Elderly Patient in a Rare Location.
PMID- 28418351
TI - [Connexin 43 expression in human brain glial tumors].
AB - AIM: To conduct an immunohistochemical (IHC) study of the expression of connexin
43 in the samples of glial tumors of various grades: gemistocytic astrocytomas
(Grade 2), oligodendrogliomas (Grade 2) and glioblastomas (Grade 4). MATERIAL AND
METHODS: The material investigated was fragments of human brain glial tumors
(grade 2 gemistocytic astrocytomas (n=2), grade 2 oligodendrogliomas (n=2), and
grade 4 glioblastomas (n=14) and those of tumor-surrounding tissue (n=4). The
material was fixed in 10% buffered formalin, dehydrated, and embedded in paraffin
according to the standard technique. IHC studies of the slices applied primary
rabbit polyclonal antibodies against connexin 43 ('Spring Bioscience', USA) and
the Dako EnVision + Peroxidase (DAB) visualization system ('Dako', Denmark).
After the immunohistochemical reaction, the cell nuclei were stained with Mayer's
hematoxylin. RESULTS: Immunohistochemistry showed the changing pattern of
connexin 43 expression as compared with intact tissue in the glial tumors.
Instead of the fine-granular expression in the thin cellular processes in the
neuropil, the tumors mainly displayed a coarse-grained cytoplasmic and even
nuclear reaction. The morphology and localization of positive structures depended
on the variant of an examined tumor. In addition, the most malignant brain
gliomas generally exhibited a reduction in the expression of connexin 43, i.e.
its quantity is inversely proportional to the degree of malignancy of the tumor.
CONCLUSION: The low connexin 43 expression levels may reflect both a reduction in
astroglial functional gap junctions and semicanals and a decrease in the amount
of the protein itself that has independently antioncogenic properties. The
observed cytoplasmic and nuclear expression of connexin 43 is most likely to be
associated with the aberrant activity of a number of kinases, such as proto
oncogene tyrosine-kinase Src or protein kinase C (PKC).
PMID- 28418352
TI - [Fatty acid synthase in the diagnosis of prostate neoplasms].
AB - : The differential diagnosis of benign and malignant changes in the prostate
presents still definite difficulties; the antibody panel existing for these
purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme
required for de novo lipogenesis. A number of studies have noted increased
expression of the gene encoding this protein in tumors and precancerous lesions
of different locations. AIM: To estimate the diagnostic value of analyzing the
expression of FASN in prostate neoplasias. MATERIAL AND METHODS: Surgical
specimens were selected for study from 71 patients with prostate cancer during
radical prostatectomy. An immunohistochemical method was used to analyze FASN
expression. RESULTS: The expression of FASN was observed to be moderate or
intensive in adenocarcinoma and high-grade prostatic intraepithelial neoplasia
(hPIN) in all the study samples while 2 cases showed none and weak expression of
AMACR. In benign lesions, the expression of this protein was identified only in 3
cases and it was characterized by a low-intensity staining. CONCLUSION: The study
has shown that the high frequency of FASN expression in hPIN and cancer and no
expression in most structures of benign hyperplasia make it possible to use this
protein as an additional marker in the differential diagnosis of prostatic
neoplasms.
PMID- 28418353
TI - [A change in the expression of membrane-associated proteins and cytoplasmic actin
isoforms in the progression of human colon tumors].
AB - : Tumor progression is a complex process that also involves the restructuring of
the actin cytoskeleton and the weakening of intercellular adhesive contacts due
to the tumor cells that pass through the epithelial-mesenchymal transition (EMT).
AIM: To identify correlations between clinical features, risk of progression
and/or recurrence of human colon adenocarcinomas (CAC), and EMT-related tumor
markers. MATERIAL AND METHODS: Descending colon and sigmoid colon adenocarcinoma
samples were examined immunohistochemically. Formalin-fixed paraffin-embedded
tissue sections were incubated with antigen-specific antibodies, then secondary
antibodies labeled with fluorochromes, and the fluorescence intensity of
microscopy images was analyzed. RESULTS: The cells of a tumor compared to those
of intact colon tissue showed a weak staining of E-cadherin in the cell-cell
contact areas. The reduced membrane staining and nuclear localization of beta
catenin were detected in moderately (G2) and poorly (G3) differentiated tumors.
There were substantially decreased beta-actin levels in almost all tumor samples
and increased gamma-actin ones, mainly in the samples belonging to stage IV
disease. CONCLUSION: A correlation was found between stage, tumor differentiation
grade, risk for relapse or progression of disease, and the impaired expression of
different EMT markers: total or partial loss of E-cadherin expression, beta
catenin reorganization in cell-cell contacts, and a change in the ratio of
cytoplasmic actin isoforms in the late stages of CAC development. We believe that
these molecular markers may have a prognostic potential.
PMID- 28418354
TI - [Clinical and morphological signs of viral damage to a kidney transplant].
AB - AIM: To compare morphological changes and results of immunohistochemical (IHC)
identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in
the biopsy specimens with their clinical manifestations in recipients of renal
transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted
using 71 needle renal transplant biopsy specimens from patients in the study
group and 10 renal biopsy specimens from those in the control group. A number of
clinical indicators were estimated. RESULTS: IHC examination revealed the
expression of adenoviral antigens more commonly in patients with posttransplant
nephritis than in recipients without nephritis or in control individuals
(p<0.05). The association of patient age and time after kidney transplantation
with the severity of viral damage was confirmed: graft loss in children occurred
within the first months of surgery (p<0.05). Polyomavirus was detected by PCR in
patients with the morphological patterns of polyomavirus nephropathy.
Determination of HSV-1 and HSV-2 in the biopsy specimens showed no significant
associations with morphological changes. CONCLUSION: By taking into account a
variety of factors that influence the development of viral nephritis,
morphological and IHC examinations should be combined with evaluation of clinical
findings.
PMID- 28418355
TI - [Morphometric features of cardiomyocytes in the ventricular septum of patients
with hypertrophic cardiomyopathy].
AB - AIM: to determine the diameter and length of cardiomyocytes (CMC) in the
ventricular septum (VS) of patients with hypertrophic cardiomyopathy (HCM) and to
analyze correlations of a change in CMC sizes with the anatomical features of the
heart in the patients. MATERIAL AND METHODS: Longitudinal sections of
intraoperative myocardial biopsy specimens taken from 23 patients aged 15-59
years with HCM were treated using immunohistochemical detection of connexin 43;
the sizes of 50 CMCs were measured; a 4-point scale was used to assess the degree
of myofibril loss (MFL) in these cells. The change in the diameter and length of
the cells during their rearrangement as MFL gradually increased, as well as the
correlations of CMC sizes with the anatomical parameters of the heart were
analyzed. RESULTS: VS CMCs from the patients with HCM were hypertrophic and were
in the early stages of rearrangement accompanied by MFL. During this
rearrangement, CMCs in some patients grew in length and, less frequently,
diameter. The average diameter of CMCs was directly correlated with VS thickness.
The average length of the cells in the CMC population with a considerable degree
of MFL also directly correlated with VS thickness. CONCLUSION: The findings could
suggest that the factor raising VS thickness in HCM may be an increase in not
only diameter of CMCs, but also in length of CMCs, which had impaired orientation
in the VS - which are oriented perpendicular to their normal tangential position.
The presence of such CMCs in the VS myocardium in patients with HCM can be
discussed due to the typical large number of myocardial areas with the impaired
parallel arrangement of CMCs.
PMID- 28418356
TI - [Pathomorphology of the ventricular germinal zone and neocortex in newborn
infants with posthemorrhagic hydrocephalus].
AB - AIM: To study the morphological features of the ventricular germinal zone and
neocortex in newborns at 22-40 weeks' gestation with posthemorrhagic
hydrocephalus. MATERIAL AND METHODS: The brains of fetuses and newborns at 22-40
weeks' gestation with posthemorrhagic hydrocephalus (n=12) were examined; a
control group included the brains with a lateral ventricle lumen width of not
more than 0.5 cm (n=30). The investigators conducted a comprehensive
pathomorphological study of the ventricular germinal zone and neocortex in the
projection field No. 6. RESULTS: Posthemorrhagic hydrocephalus is characterized
by a deceleration in the reduction of the ventricular germinal zone and by the
corresponding level of differentiation of the cortex and neurons to gestational
age in the presence of the physiological expression of reelin in the Cajal
Retzius neurons and in that of the impaired expression of matrix
metalloproteinase 9 (a decrease) and the glial protein S-100 (an increase) in the
cells of the ventricular germinal zone. CONCLUSION: The morphological features of
the ventricular germinal zone and neocortex of fetuses and newborns at 22-40
weeks' gestation with posthemorrhagic hydrocephalus should be considered as
morphological differential diagnostic criteria for the disease.
PMID- 28418357
TI - [Renal morphological changes in experimental oxalate nephrolithiasis].
AB - AIM: To evaluate renal morphological changes in the early stages of lithogenic
processes and during urinary correction of urine with oxalate-chelating compounds
(sodium citrate). MATERIAL AND METHODS: An experimental model of oxalate
nephrolithiasis was performed on 80 male Wistar rats weighing 180 to 250 g. Rat
kidneys were morphologically and ultrastructurally studied. Immunohistochemical
techniques were applied to study the features of development of endoplasmic
reticulum stress. RESULTS: There were histotopographic changes in the renal
tissue elements in the early stages of development of lithogenic processes
accompanied by characteristic ultrastructural changes in the epithelium of the
renal tubules and collecting ducts: by expansion of elements in the granular
endoplasmic network, by mitochondrial damage with formation of large, ampullary
extended cristae, and by emergence of autolysosomes. Signs of development of
endoplasmic reticulum stress with activation of protein GADD153 were found, which
deteriorated the cell lining of the nephron tubules and collecting ducts.
CONCLUSION: In the early stages of development of lithogenic processes, there are
stereotypic ultrastructural and histotopographic changes in the epithelium of the
nephron tubules and collecting ducts, which contribute to the progression of
stone formation processes and to the disruption of cellular homeostasis with
activation of endoplasmic reticulum stress, synthesis impairment, or post
translational modifications in modulator proteins of lithogenesis.
PMID- 28418358
TI - [Tumors of the kidney. The new 2016 WHO classification of tumors of the
genitourinary system].
AB - The article deals with the innovations available in the 2016 World Health
Organization (WHO) classification of renal tumors, which has replaced the
previous 2004 WHO classification. The review highlights the key aspects necessary
for practicing histopathologists who work in specialized cancer centers or
multidisciplinary hospitals diagnosing renal tumors. How to choose a system for
determining the malignancy grade of renal tumors is considered separately.
PMID- 28418359
TI - [A rare concurrence of polymyalgia rheumatica and AA-amyloidosis].
AB - Polymyalgia rheumatica (PMR) is a rare chronic inflammatory disease. It
predominantly affects the elderly. The disease has a slow onset, pain and
stiffness in the muscles of the shoulder and pelvic girdle, fever, weight loss,
and a high acute-phase inflammatory response. The disease is concurrent with
giant cell arteritis in a quarter of cases, which allows some authors to consider
them as two different manifestations of the same pathological process. The
kidneys are rarely involved. This disease is rarely complicated by AA
amyloidosis. The authors describe a case of RPM in a patient who has developed
secondary AA amyloidosis.
PMID- 28418360
TI - [Role of telocytes in the heart in health and diseases].
AB - This review summarizes the data available in the literature on the development,
structure, and function of telocytes (TCs) and their role in the heart in health
and diseases. At the present time, TCs have been found in many organs of mammals
and humans. TC is a small oval cell that contains a nucleus surrounded by small
amounts of cytoplasm, with extremely long and thin processes named telopodias.
TCs have unique ultrastructural and immunohistochemical features; double positive
labeling for CD34/PDGFR-beta and CD34/vimentin is suitable for their
identification. The role of TCs in the heart at different study stages is the
subject of debate. There are currently available data on a decline in the number
of cardiac TCs in patients with various heart diseases. Relying on a number of
investigations showing that TCs are present in the subepicardial stem cell
niches, the authors consider a hypothesis for the key role of cardiac TCs in the
regeneration and reparation of the heart.
PMID- 28418361
TI - [Intraoperative formation of the valved conduit in aortic root surgery].
AB - AIM: To present an experience of intraoperative manufacture of the valved conduit
in aortic root surgery in the Department of Cardiac Surgery of Sechenov First
Moscow State Medical University. MATERIAL AND METHODS: In our department aortic
valve and ascending aortic replacement using intraoperatively manufactured valved
conduit was performed in 11 patients for the period 2012-2016. Technical aspects,
choice of vascular prosthesis size and type of fixation to achieve optimal
hemodynamics and adequate impermeability of stitches are described. RESULTS:
Intraoperative manufacture of the valved conduit is successfully reproducible
technique with good early and remote results. CONCLUSION: Described surgical
method is not accompanied by increased postoperative blood loss, CPB and aortic
cross-clamping time.
PMID- 28418362
TI - [Individual learning curves for microsurgical myocardial revascularization].
AB - AIM: To create individual learning curves for microsurgical myocardial
revascularization. MATERIAL AND METHODS: It was analyzed duration of the
individual stages of the first 100 CABG procedures which were performed using
microsurgical technique and surgical microscope. Graphs reflecting correlation
between duration of the individual surgical stages and their number were framed.
RESULTS: Improvement in distal anastomosis time, aortic cross-clamping time,
cardiopulmonary bypass time and duration of surgery was observed with increased
surgeon's experience. CONCLUSION: Individual learning curves objectively
characterize the learning process of microsurgical myocardial revascularization,
allow to estimate the time need for improvement of cardiac surgeons'
qualification and demonstrate dates for achieving average surgical quality during
learning the technique.
PMID- 28418363
TI - [Correlation of the intra-operative neuromonitoring data and emg-characteristics
of post-operative motor deficit in patients with spinal deformities].
AB - AIM: To correlate electroneuromyigraphic (ENMG) manifestations of post-operative
motor deficit developed in patients after spinal deformity correction with
qualitative evaluation of the severity of intra-operative pyramidal disorders
according to protocol of intra-operative neuromonitoring (IONM). MATERIAL AND
METHODS: ENMG data of 87 patients aged 6-43 years with spinal deformities of
different etiology were analyzed before and after surgical correction and were
correlated with intra-operative neuromonitoring course. RESULTS: We have
identified five types of the intraoperative reaction of pyramidal system to
surgical aggression. Severity of postoperative motor deficit was the most
pronounced after the fifth type of reaction according to electromyography
(complete prolonged oppression of motor evoked potentials). CONCLUSION: We
suggested the scale of intra-operative pyramidal disorders severity that is
satisfactorily correlated with functional surgical outcomes which are reflected
in the dynamics of particular and integral characteristics of voluntary and
evoked bioelectrical activity of the lower limb muscles. This fact makes possible
to use safely the above-mentioned protocol for IONM, to predict postoperative
motor disorders and to formulate reasonably the recommendations for postoperative
management.
PMID- 28418364
TI - [Evolution of complex treatment of patients with non-specific pleural empyema].
AB - AIM: To analyze long-term own experience of NPE treatment in view of evolution of
surgical sanitation of pleural cavity. MATERIAL AND METHODS: The analysis
included 5115 patients with NPE for the last 39 years (1977-2015). Morbidity,
features of microflora of purulent exudate, changes in the structure of surgical
methods were assessed. The role of computed tomography in the diagnostic
algorithm and treatment of NPE was studied. RESULTS: The evolution of NPE
surgical management includes introduction of video technologies, thermal surgical
instruments and widespread use of computed tomography in the diagnosis of pleural
empyema. So, significant reduction of patients who were discharged with residual
cavities was observed. Postoperative mortality was 19.5% for the period 1977-1996
when traumatic open surgery was used. At the same time there were no deaths
within 1997-2015 due to introduction of VATS pleural drainage. Overall mortality
decreased from 4.9% to 3.2% for the same period due to reduced postoperative
complications. CONCLUSION: The introduction of minimally invasive technologies,
new thermal surgical instruments changed management of NPE patients, reduced the
number of traumatic open procedures. So, improved outcomes were achieved.
PMID- 28418365
TI - [Surgical strategy for locally-advanced right-sided colonic cancer].
AB - AIM: To present early and remote surgical outcomes in patients with locally
advanced right-sided colonic cancer, invasion of pancreatic head and/or duodenal
wall. MATERIAL AND METHODS: Early and remote surgical outcomes were analyzed in
27 patients who underwent gastropancreatoduodenectomy combined with right-sided
hemicolectomy (ileotransversostomy extirpation) for locally-advanced right-sided
colonic cancer. RESULTS: Mean time of surgery was 300 (240-460) minutes,
intraoperative blood loss - 2000 (500-7200) ml. Postoperative complications were
observed in 15 (55.6%) patients. 3 (11.1%) patients died in early postoperative
period. Overall 1-, 3- and 5-year survival was 92.7%, 48% and 36,5% respectively.
Median was 33 months. CONCLUSION: Advanced combined surgery for locally-advanced
right-sided colonic cancer, invasion of pancreatic head and/or duodenal wall is
associated with acceptable incidence of postoperative complications, early and
long-term mortality.
PMID- 28418366
TI - [The role of 3D-CT in surgery for pancreatic ductal adenocarcinoma: post
processing and tissue volume calculation].
AB - AIM: To define the indications for pancreatoduodenectomy using 3D CT-imaging, to
calculate the volume of damaged and intact tissues and to determine type of
surgery depending on severity of disease in case of ductal pancreatic
adenocarcinoma. MATERIAL AND METHODS: Retrospective analysis of CT-scans of 30
patients with ductal pancreatic adenocarcinoma was performed. In groups 1 and 2
by 15 patients total pancreatectomy and pancreatoduodenectomy were made
respectively. All patients underwent contrast-enhanced CT examination (Brilliance
iCT, Phillips) followed post-processing on Brilliance Workspace Portal platform.
All data were assessed by two reviewers. RESULTS: In group 1 CT volume of the
tumor was 24+/-19 cm3 (32% of total pancreas), in group 2 - 9.8+/-6 cm3 (16% of
total pancreas). CT-volume of celiacomesenteric arteries and portal system was
25.8+/-10 mm/59.5+/-18.9 mm and 23.3+/-6/49.9+/-14.7 mm in groups 1 and 2
respectively. Greater volume of tumor was significantly associated with increased
portal system (p<0.03). Sensitivity, specificity and accuracy of determining of
tumor location were increased up to 94%, 50% and 80% respectively in group 1.
There were no cases of wrong localization in group 2. Data of both reviewers were
similar. CONCLUSION: Total pancreatectomy is advisable for pancreatic
adenocarcinoma if its volume is over 31.8% of total pancreas according to 3D CT
scans. 3D-modeling improves preoperative assessment of resectability, accuracy of
determining of tumor localization and identifying vascular invasion.
PMID- 28418367
TI - [The use of computed tomography in the diagnosis of acute appendicitis].
AB - AIM: To present the use of computed tomography in the diagnosis of acute
appendicitis. MATERIAL AND METHODS: The study was conducted in 139 patients who
were hospitalized with suspected acute appendicitis. However, the diagnosis was
not clearly confirmed by clinical and ultrasonic data. RESULTS: Computed
tomography confirmed/rejected presumptive diagnosis in 90.8% of patients. It was
concluded that CT has high diagnostic accuracy to confirm acute appendicitis.
PMID- 28418368
TI - [Differentiated approach to the treatment of large hernial defects of the
anterior abdominal wall in children (clinical observations)].
AB - AIM: To present an experience of treatment of children with large hernial defects
of the anterior abdominal wall. MATERIAL AND METHODS: This article describes
management of 43 children with large (n=31) and giant (n=12) ventral hernia who
were at N.F. Filatov Children's City Hospital #13 for the period 2005-2015. All
patients underwent surgical correction using local tissues in 'edge to edge'
fashion (n=23), aponeurosis dublication of 'coat floors' type (n=14) and
biological implant 'Permacol' (n=6). Etiological causes of ventral hernias in
children were comprehensively analyzed. Optimal time for surgical treatment and
features of viscero-abdominal disproportion were discussed. CONCLUSION: Early
restoration of anatomical and functional structures of the anterior abdominal
wall is necessary for good cosmetic result and prevention of recurrent ventral
hernia. We presented three clinical examples of commonly used surgical procedures
in children including anterior abdominal wall repair using biological material
'Permacol'.
PMID- 28418369
TI - [Optimization of tissue reparation at treatment by Remaxol].
AB - AIM: Studying influence of remaxol on reparative process of tissue reparation in
a laparotomy wound. MATERIAL AND METHODS: 90 patients with the acute appendicitis
complicated by local peritonitis in the early postoperative period are examined.
50 patients received traditional therapy. Therapy of other 40 patients included
Remaxol (intravenous introduction, daily within 5 days, of 400 ml). RESULTS AND
CONCLUSION: It is established that Remaxol optimizes the course of reparative
process in laparotomy wound that was confirmed with data of tenziomety and wound
exudate cytological research. Efficiency of a Remaxol is based on its capability
to improve microcirculation, antiedematous action and its capability to reduce
excessive intensity peroxide oxidation of membrane lipids, phospholipase activity
and the phenomena of a hypoxia.
PMID- 28418370
TI - [Current study aimed to highlight extent of clot resolution in deep veins and its
association with anticoagulation pattern in VTE patients].
AB - MATERIAL AND METHODS: Data of 70 patients with acute VTE of lower extremities
(iliofemoral level) was analyzed. There were 42 patients in the study group which
were treated with rivaroxaban (15 mg BID for 21 days, 20 mg od from day 22); 28
patients were in control group treated with conventional therapy (LMWH/VKA).
Extent of clot resolution was assessed on ultrasound. Data was collected at a day
of VTE diagnosis and further at 1, 3, 6 month. RESULTS: The results of the study
demonstrated, that patients treated with rivaroxaban had earlier recanalization
and extent of clot resolution was higher than in patients treated with
conventional therapy. After one year of treatment 73,8% of patients in the study
group had total or good recanalization compared to 37% of patients in the control
group.
PMID- 28418371
TI - [Intersphincteric resection for stage I-III low rectal cancer is an oncologically
safe alternative to extralevator abdomino-perineal rectal resection].
AB - AIM: To compare oncologic efficiency of intersphincteric resections and
extralevator abdominoperineal excisions in surgical treatment of low rectal
cancer. METHODS: Between 2006 and 2015 in Department of colorectal and pelvic
floor surgery (Russian scientific center of surgery n.a. acad. B.V. Petrovsky)
and in Clinic of Colorectal and Minimally invasive surgery (Sechenov First Moscow
State Medical University) 40 consecutive patients underwent intersphincteric
resection (ISR) and 31 underwent extralevator abdominoperineal excision (EAPE).
All patients had low rectal cancer staged I-III within 5 cm from the anal verge.
RESULTS: Circular resection margin >1 mm was achieved in 95% and 84% of patients
after ISR and EAPR correspondingly (p=0.002), negative distal resection margin
was achieved in 95% of ISR patients. In ISR group mean distance from the lower
tumor edge to the distal resection margin was 1,17+/-0,78 cm. Colo-anal
anastomosis leak rate was 17%. The 3-year disease-free survival in ISR group was
97%, 5-year disease-free survival was 93%. The 5-year disease-free survival in
stage III for ISR group was 71,4%. In 98% of ISR patients complete restoration of
bowel continuity was performed.
PMID- 28418373
TI - [Surgical strategy in rectal resection for cancer].
PMID- 28418372
TI - [The current view for antisecretory therapy in acute pancreatitis].
PMID- 28418374
TI - [Intestinal fistula after anterior abdominal wall hernia repair with composite
prosthesis].
PMID- 28418375
TI - [Technical aspects in surgery for acute adhesive intestinal obstruction].
PMID- 28418376
TI - A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop
formation.
AB - Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non
canonical RNAs that arise through a form of alternative splicing (AS) called back
splicing. These single-stranded, covalently-closed circRNA molecules have been
identified in all eukaryotic kingdoms of life1, yet their functions have remained
elusive. Here, we report that circRNAs can be used as bona fide biomarkers of
functional, exon-skipped AS variants in Arabidopsis, including in the homeotic
MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs
derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the
cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving
floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we
show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus,
forming an RNA:DNA hybrid, or R-loop, whereas the linear RNA equivalent bound
significantly more weakly to DNA. R-loop formation results in transcriptional
pausing, which has been shown to coincide with splicing factor recruitment and
AS2-4. This report presents a novel mechanistic insight for how at least a subset
of circRNAs probably contribute to increased splicing efficiency of their cognate
exon-skipped messenger RNA and provides the first evidence of an organismal-level
phenotype mediated by circRNA manipulation.
PMID- 28418378
TI - Polysaccharide structure: A hint from gut bacteria.
PMID- 28418377
TI - The Magnaporthe oryzae nitrooxidative stress response suppresses rice innate
immunity during blast disease.
AB - Understanding how microorganisms manipulate plant innate immunity and colonize
host cells is a major goal of plant pathology. Here, we report that the fungal
nitrooxidative stress response suppresses host defences to facilitate the growth
and development of the important rice pathogen Magnaporthe oryzae in leaf cells.
Nitronate monooxygenases encoded by NMO genes catalyse the oxidative
denitrification of nitroalkanes. We show that the M. oryzae NMO2 gene is required
for mitigating damaging lipid nitration under nitrooxidative stress conditions
and, consequently, for using nitrate and nitrite as nitrogen sources. On plants,
the Deltanmo2 mutant strain penetrated host cuticles like wild type, but invasive
hyphal growth in rice cells was restricted and elicited plant immune responses
that included the formation of cellular deposits and a host reactive oxygen
species burst. Development of the M. oryzae effector-secreting biotrophic
interfacial complex (BIC) was misregulated in the Deltanmo2 mutant. Inhibiting or
quenching host reactive oxygen species suppressed rice innate immune responses
and allowed the Deltanmo2 mutant to grow and develop normally in infected cells.
NMO2 is thus essential for mitigating nitrooxidative cellular damage and, in rice
cells, maintaining redox balance to avoid triggering plant defences that impact
M. oryzae growth and BIC development.
PMID- 28418379
TI - Exercise contagion in a global social network.
AB - We leveraged exogenous variation in weather patterns across geographies to
identify social contagion in exercise behaviours across a global social network.
We estimated these contagion effects by combining daily global weather data,
which creates exogenous variation in running among friends, with data on the
network ties and daily exercise patterns of ~1.1M individuals who ran over 350M
km in a global social network over 5 years. Here we show that exercise is
socially contagious and that its contagiousness varies with the relative activity
of and gender relationships between friends. Less active runners influence more
active runners, but not the reverse. Both men and women influence men, while only
women influence other women. While the Embeddedness and Structural Diversity
theories of social contagion explain the influence effects we observe, the
Complex Contagion theory does not. These results suggest interventions that
account for social contagion will spread behaviour change more effectively.
PMID- 28418380
TI - Crop breeding: Turning a lawn into a field.
PMID- 28418381
TI - Sparse panicle1 is required for inflorescence development in Setaria viridis and
maize.
AB - Setaria viridis is a rapid-life-cycle model panicoid grass. To identify genes
that may contribute to inflorescence architecture and thus have the potential to
influence grain yield in related crops such as maize, we conducted an N-nitroso-N
methylurea (NMU) mutagenesis of S. viridis and screened for visible inflorescence
mutant phenotypes. Of the approximately 2,700 M2 families screened, we identified
four recessive sparse panicle mutants (spp1-spp4) characterized by reduced and
uneven branching of the inflorescence. To identify the gene underlying the sparse
panicle1 (spp1) phenotype, we performed bulked segregant analysis and deep
sequencing to fine map it to an approximately 1 Mb interval. Within this
interval, we identified disruptive mutations in two genes. Complementation tests
between spp1 and spp3 revealed they were allelic, and deep sequencing of spp3
identified an independent disruptive mutation in SvAUX1 (AUXIN1), one of the two
genes in the ~1 Mb interval and the only gene disruption shared between spp1 and
spp3. SvAUX1 was found to affect both inflorescence development and root
gravitropism in S. viridis. A search for orthologous mutant alleles in maize
confirmed a very similar role of ZmAUX1 in maize, which highlights the utility of
S. viridis in accelerating functional genomic studies in maize.
PMID- 28418383
TI - Marking HIV.
PMID- 28418382
TI - Structure of the hexagonal surface layer on Caulobacter crescentus cells.
AB - Many prokaryotic cells are encapsulated by a surface layer (S-layer) consisting
of repeating units of S-layer proteins. S-layer proteins are a diverse class of
molecules found in Gram-positive and Gram-negative bacteria and most archaea1-5.
S-layers protect cells from the outside, provide mechanical stability and also
play roles in pathogenicity. In situ structural information about this highly
abundant class of proteins is scarce, so atomic details of how S-layers are
arranged on the surface of cells have remained elusive. Here, using purified
Caulobacter crescentus' sole S-layer protein RsaA, we obtained a 2.7 A X-ray
structure that shows the hexameric S-layer lattice. We also solved a 7.4 A
structure of the S-layer through electron cryotomography and sub-tomogram
averaging of cell stalks. The X-ray structure was docked unambiguously into the
electron cryotomography map, resulting in a pseudo-atomic-level description of
the in vivo S-layer, which agrees completely with the atomic X-ray lattice model.
The cellular S-layer atomic structure shows that the S-layer is porous, with a
largest gap dimension of 27 A, and is stabilized by multiple Ca2+ ions bound near
the interfaces. This study spans different spatial scales from atoms to cells by
combining X-ray crystallography with electron cryotomography and sub-nanometre
resolution sub-tomogram averaging.
PMID- 28418384
TI - Dietary short-chain fatty acids protect against type 1 diabetes.
PMID- 28418385
TI - Speaking out about gender imbalance in invited speakers improves diversity.
PMID- 28418386
TI - Circulating potential.
PMID- 28418388
TI - Glioma immune evasion.
PMID- 28418389
TI - The immune system as a social network.
PMID- 28418387
TI - Mitochondria are the powerhouses of immunity.
AB - Recent evidence indicates that mitochondria lie at the heart of immunity.
Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the
mitochondrial outer membrane is a platform for signaling molecules such as MAVS
in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis,
fusion and fission have roles in aspects of immune-cell activation. Most
important, Krebs cycle intermediates such as succinate, fumarate and citrate
engage in processes related to immunity and inflammation, in both innate and
adaptive immune cells. These discoveries are revealing mitochondrial targets that
could potentially be exploited for therapeutic gain in inflammation and cancer.
PMID- 28418391
TI - Vitamin C for microglia.
PMID- 28418390
TI - IRE1 gives weight to obesity-associated inflammation.
PMID- 28418393
TI - Macrophage dynamics.
PMID- 28418392
TI - Gene-enhancer variants reveal diverse TCR-mediated differentiation.
PMID- 28418394
TI - PD-1 targets CD28.
PMID- 28418395
TI - An analysis of ideal and actual time to surgery after traumatic spinal cord
injury in Canada.
AB - STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon
survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the
timing of decompression/stabilization for spinal cord injury and actual practice.
Discrepancies in surgical timing and barriers to ideal timing of surgery were
explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord
Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical
management. Following data collection, a survey was distributed to Canadian
surgeons, asking for perceived to be the optimal and actual timings of surgery.
Discrepancies between actual data and surgeon survey responses were then compared
using chi2 tests and logistic regression. RESULTS: The majority of injury
patterns identified in the registry were treated operatively. ASIA Impairment
Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR
data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities
between what surgeons identified as ideal, actual current practice and RHSCIR
data were demonstrated. A great majority of surgeons (93.0%) believed surgery
under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS
A/B/C/D injuries. Definitive surgical management within 24 h was actually
accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal
surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was
identified, but not accomplished. Discrepancies between the opinions on the
optimal and actual timing of surgery in tSCI patients suggest the need for
strategies for knowledge translation and reduction of administrative barriers to
early surgery.
PMID- 28418396
TI - Essential gains and health after upper-limb tetraplegia surgery identified by the
International classification of functioning, disability and health (ICF).
AB - STUDY DESIGN: A questionnaire-based survey. OBJECTIVES: To describe functional
gains and health following upper-limb tetraplegia surgery using the International
Classification of Functioning, Disability and Health (ICF) as a reference and to
explore interconnections across different dimensions of functioning and health.
SETTING: A specialized center for advanced reconstruction of extremities at
Sahlgrenska University Hospital, Gothenburg, Sweden. METHODS: Fifty-seven
individuals who participated in a satisfaction survey were included in the
present study. Besides questions concerned with the respondents' satisfaction
with different aspects of surgery, the measures included perceived overall health
status (EQ-VAS) and achieved grip strength. Univariate analyses were used to
explore interconnections between measures. RESULTS: The gains could be
subcategorized and linked to the ICF domains 'mobility', 'self-care',
'communication', 'domestic life', and 'community, social and civic life', with
'handling objects' and 'maneuvering a wheelchair' as the most frequently reported
gains. The mean EQ-VAS score was 67+/-22. No significant correlation was shown
between grip strength and activity gains, nor between grip strength and perceived
overall health. The degree of satisfaction was, however, associated with self
reported overall health among participants. CONCLUSION: The functional gains
achieved after tetraplegia surgery could be applied to the ICF constructs' body
functions/structures and activity with possible implications on participation.
The overall health perception was relatively high and could be linked to the
degree of satisfaction among participants. Muscle strength is not necessarily
transferable to activity performance. This emphasizes the importance of
addressing factors other than strength in the post-surgical rehabilitation and
assessments.
PMID- 28418397
TI - Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune
response in Drosophila and mice.
AB - Immune homeostasis is a prerequisite to protective immunity against
gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling
(tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals)
is indispensable for intestinal immunity against invading bacteria. However, how
this local antimicrobial immune response contributes to inflammatory regulation
remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a
subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF)
complex) are susceptible to infection as a result of hyper-inflammation rather
than bacterial overload. Detailed analysis shows that Bap180 is induced by the
IMD-Relish response to both enteropathogenic and commensal bacteria. Upregulated
Bap180 can feed back to restrain overreactive IMD signalling, as well as to
repress the expression of the pro-inflammatory gene eiger (TNF), a critical step
to prevent excessive tissue damage and elongate the lifespan of flies, under
pathological and physiological conditions, respectively. Furthermore, intestinal
targeting of Baf180 renders mice susceptible to a more aggressive infectious
colitis caused by Citrobacter rodentium. Together, Bap180 and Baf180 serve as a
conserved transcriptional repressor that is critical for the maintenance of
innate immune homeostasis in the intestines.
PMID- 28418398
TI - Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in
women.
AB - Oxytocin may influence various human behaviors and the connectivity across
subcortical and cortical networks. Previous oxytocin studies are male biased and
often constrained by task-based inferences. Here, we investigate the impact of
oxytocin on resting-state connectivity between subcortical and cortical networks
in women. We collected resting-state functional magnetic resonance imaging (fMRI)
data on 26 typically developing women 40 min following intranasal oxytocin
administration using a double-blind placebo-controlled crossover design.
Independent components analysis (ICA) was applied to examine connectivity between
networks. An independent analysis of oxytocin receptor (OXTR) gene expression in
human subcortical and cortical areas was carried out to determine plausibility of
direct oxytocin effects on OXTR. In women, OXTR was highly expressed in striatal
and other subcortical regions, but showed modest expression in cortical areas.
Oxytocin increased connectivity between corticostriatal circuitry typically
involved in reward, emotion, social communication, language and pain processing.
This effect was 1.39 standard deviations above the null effect of no difference
between oxytocin and placebo. This oxytocin-related effect on corticostriatal
connectivity covaried with autistic traits, such that oxytocin-related increase
in connectivity was stronger in individuals with higher autistic traits. In sum,
oxytocin strengthened corticostriatal connectivity in women, particularly with
cortical networks that are involved in social-communicative, motivational and
affective processes. This effect may be important for future work on neurological
and psychiatric conditions (for example, autism), particularly through
highlighting how oxytocin may operate differently for subsets of individuals.
PMID- 28418399
TI - Restoring effects of oxytocin on the attentional preference for faces in autism.
AB - Reduced attentional preference for faces and symptoms of social anxiety are
common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers
anxiolytic functions and enhances eye gaze, facial emotion recognition and neural
correlates of face processing in ASD. Here we investigated whether a single dose
of oxytocin increases attention to faces in ASD. As a secondary question, we
explored the influence of social anxiety on these effects. We tested for
oxytocin's effects on attention to neutral faces as compared to houses in a
sample of 29 autistic individuals and 30 control participants using a dot-probe
paradigm with two different presentation times (100 or 500 ms). A single dose of
24 IU oxytocin was administered in a randomized, double-blind placebo-controlled,
cross-over design. Under placebo, ASD individuals paid less attention to faces
presented for 500 ms than did controls. Oxytocin administration increased the
allocation of attention toward faces in ASD to a level observed in controls.
Secondary analyses revealed that these oxytocin effects primarily occurred in ASD
individuals with high levels of social anxiety who were characterized by
attentional avoidance of faces under placebo. Our results confirm a positive
influence of intranasal oxytocin on social attention processes in ASD. Further,
they suggest that oxytocin may in particular restore the attentional preference
for facial information in ASD individuals with high social anxiety. We conclude
that oxytocin's anxiolytic properties may partially account for its positive
effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and
facial emotion recognition.
PMID- 28418400
TI - Short telomere length is associated with impaired cognitive performance in
European ancestry cohorts.
AB - The association between telomere length (TL) dynamics on cognitive performance
over the life-course is not well understood. This study meta-analyses
observational and causal associations between TL and six cognitive traits, with
stratifications on APOE genotype, in a Mendelian Randomization (MR) framework.
Twelve European cohorts (N=17 052; mean age=59.2+/-8.8 years) provided results
for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive
function, mini-mental state exam (MMSE), processing speed by digit symbol
substitution test (DSST), visuospatial functioning, memory and executive
functioning (STROOP). In addition, a genetic risk score (GRS) for TL including
seven known genetic variants for TL was calculated, and used in associations with
cognitive traits as outcomes in all cohorts. Observational analyses showed that
longer telomeres were associated with better scores on DSST (beta=0.051 per s.d.
increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE
(beta=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (beta=-0.053; 95%
CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE E4 non
carriers (beta=0.081; 95% CI: 0.045, 0.117; P=1.0 * 10-5), whereas carriers
performed better in STROOP (beta=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal
associations were found for STROOP only (beta=-0.598 per s.d.-increase of TL; 95%
CI: -1.125, -0.072; P=0.026), with a larger effect in E4-carriers (beta=-0.699;
95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE
summary statistics showed causal effects between TL and general cognitive
function and DSST, but not with STROOP. In conclusion, we suggest causal effects
from longer TL on better cognitive performance, where APOE E4-carriers might be
at differential risk.
PMID- 28418401
TI - Weak associations between pubertal development and psychiatric and behavioral
problems.
AB - Pubertal development has been associated with adverse outcomes throughout
adolescence and adulthood. However, much of the previous literature has
categorized outcome variables and pubertal timing measures for ease of mean
difference or odds ratio interpretation. We use a UK-representative sample of
over 5000 individuals drawn from the Twins Early Development Study to extend this
literature by adopting an individual differences approach and emphasizing effect
sizes. We investigate a variety of psychiatric and behavioral measures collected
longitudinally at ages 11, 14 and 16, for multiple raters and for males and
females separately. In addition, we use two measures of pubertal development: the
Pubertal Development Scale at each age, as well as the age of menarche for girls.
We found that pubertal development, however assessed, was linearly associated
with a range of psychiatric and behavioral outcomes; however, the effect sizes of
these associations were modest for both males and females with most correlations
between -0.10 and 0.10. Our systematic analysis of associations between pubertal
development, and psychiatric and behavioral problems is the most comprehensive to
date. The results showing linearity of the effects of pubertal development
support an individual differences approach, treating both pubertal development
and associated outcomes as continuous rather than categorical variables. We
conclude that pubertal development explains little variance in psychiatric and
behavioral outcomes (<1% on average). The small effect sizes indicate that the
associations are weak and should not warrant major concern at least in non
clinical populations.
PMID- 28418402
TI - Transcriptome sequencing study implicates immune-related genes differentially
expressed in schizophrenia: new data and a meta-analysis.
AB - We undertook an RNA sequencing (RNAseq)-based transcriptomic profiling study on
lymphoblastoid cell lines of a European ancestry sample of 529 schizophrenia
cases and 660 controls, and found 1058 genes to be differentially expressed by
affection status. These differentially expressed genes were enriched for
involvement in immunity, especially the 697 genes with higher expression in
cases. Comparing the current RNAseq transcriptomic profiling to our previous
findings in an array-based study of 268 schizophrenia cases and 446 controls
showed a highly significant positive correlation over all genes. Fifteen (18%) of
the 84 genes with significant (false discovery rate<0.05) expression differences
between cases and controls in the previous study and analyzed here again were
differentially expressed by affection status here at a genome-wide significance
level (Bonferroni P<0.05 adjusted for 8141 analyzed genes in total, or P<~6.1 *
10-6), all with the same direction of effect, thus providing corroborative
evidence despite each sample of fully independent subjects being studied by
different technological approaches. Meta-analysis of the RNAseq and array data
sets (797 cases and 1106 controls) showed 169 additional genes (besides those
found in the primary RNAseq-based analysis) to be differentially expressed, and
provided further evidence of immune gene enrichment. In addition to strengthening
our previous array-based gene expression differences in schizophrenia cases
versus controls and providing transcriptomic support for some genes implicated by
other approaches for schizophrenia, our study detected new genes differentially
expressed in schizophrenia. We highlight RNAseq-based differential expression of
various genes involved in neurodevelopment and/or neuronal function, and discuss
caveats of the approach.
PMID- 28418403
TI - Assessing the presence of shared genetic architecture between Alzheimer's disease
and major depressive disorder using genome-wide association data.
AB - Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in
older age and frequently co-occur. Numerous phenotypic studies based on clinical
diagnoses suggest that a history of depression increases risk of subsequent AD,
although the basis of this relationship is uncertain. Both illnesses are
polygenic, and shared genetic risk factors could explain some of the observed
association. We used genotype data to test whether MDD and AD have an overlapping
polygenic architecture in two large population-based cohorts, Generation
Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25
118), and whether age of depression onset influences any relationship. Using two
complementary techniques, we found no evidence that the disorders are influenced
by common genetic variants. Using linkage disequilibrium score regression with
genome-wide association study (GWAS) summary statistics from the International
Genomics of Alzheimer's Project, we report no significant genetic correlation
between AD and MDD (rG=-0.103, P=0.59). Polygenic risk scores (PRS) generated
using summary data from International Genomics of Alzheimer's Project (IGAP) and
the Psychiatric Genomics Consortium were used to assess potential pleiotropy
between the disorders. PRS for MDD were nominally associated with participant
recalled AD family history in GS:SFHS, although this association did not survive
multiple comparison testing. AD PRS were not associated with depression status or
late-onset depression, and a survival analysis showed no association between age
of depression onset and genetic risk for AD. This study found no evidence to
support a common polygenic structure for AD and MDD, suggesting that the
comorbidity of these disorders is not explained by common genetic variants.
PMID- 28418404
TI - A pathway linking reward circuitry, impulsive sensation-seeking and risky
decision-making in young adults: identifying neural markers for new
interventions.
AB - High trait impulsive sensation seeking (ISS) is common in 18-25-year olds, and is
associated with risky decision-making and deleterious outcomes. We examined
relationships among: activity in reward regions previously associated with ISS
during an ISS-relevant context, uncertain reward expectancy (RE), using fMRI; ISS
impulsivity and sensation-seeking subcomponents; and risky decision-making in
100, transdiagnostically recruited 18-25-year olds. ISS, anhedonia, anxiety,
depression and mania were measured using self-report scales; clinician
administered scales also assessed the latter four. A post-scan risky decision
making task measured 'risky' (possible win/loss/mixed/neutral) fMRI-task versus
'sure thing' stimuli. 'Bias' reflected risky over safe choices. Uncertain RE
related activity in left ventrolateral prefrontal cortex and bilateral ventral
striatum was positively associated with an ISS composite score, comprising
impulsivity and sensation-seeking-fun-seeking subcomponents (ISSc; P?0.001). Bias
positively associated with sensation seeking-experience seeking (ES; P=0.003).
This relationship was moderated by ISSc (P=0.009): it was evident only in high
ISSc individuals. Whole-brain analyses showed a positive relationship between:
uncertain RE-related left ventrolateral prefrontal cortical activity and ISSc;
uncertain RE-related visual attention and motor preparation neural network
activity and ES; and uncertain RE-related dorsal anterior cingulate cortical
activity and bias, specifically in high ISSc participants (all ps<0.05, peak
level, family-wise error corrected). We identify an indirect pathway linking
greater levels of uncertain RE-related activity in reward, visual attention and
motor networks with greater risky decision-making, via positive relationships
with impulsivity, fun seeking and ES. These objective neural markers of high ISS
can guide new treatment developments for young adults with high levels of this
debilitating personality trait.
PMID- 28418410
TI - Latin American Society for Pediatric Research (LASPR) Selected Abstracts from the
LIV Annual Meeting.
PMID- 28418406
TI - Large near-term projected snowpack loss over the western United States.
AB - Peak runoff in streams and rivers of the western United States is strongly
influenced by melting of accumulated mountain snowpack. A significant decline in
this resource has a direct connection to streamflow, with substantial economic
and societal impacts. Observations and reanalyses indicate that between the 1980s
and 2000s, there was a 10-20% loss in the annual maximum amount of water
contained in the region's snowpack. Here we show that this loss is consistent
with results from a large ensemble of climate simulations forced with natural and
anthropogenic changes, but is inconsistent with simulations forced by natural
changes alone. A further loss of up to 60% is projected within the next 30 years.
Uncertainties in loss estimates depend on the size and the rate of response to
continued anthropogenic forcing and the magnitude and phasing of internal decadal
variability. The projected losses have serious implications for the hydropower,
municipal and agricultural sectors in the region.
PMID- 28418405
TI - Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal
neuroblast proliferation.
AB - Dampened adenosine A2A receptor (A2AR) function has been implicated in addiction
through enhancement of goal-directed behaviors. However, the contribution of the
A2AR to the control of impulsive reward seeking remains unknown. Using mice that
were exposed to differential reward of low rate (DRL) schedules during Pavlovian
conditioning, second-order schedule discrimination, and the 5-choice serial
reaction time task (5-CSRTT), we demonstrate that deficits of A2AR function
promote impulsive responses. Antagonism of the A2AR lowered ERK1 and ERK2
phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity
during Pavlovian-conditioning and the 5-CSRTT. Remarkably, inhibition of ERK1 and
ERK2 phosphorylation by U0126 in the dHip prior to Pavlovian-conditioning
exacerbated impulsive reward seeking. Moreover, we found decreased A2AR
expression, and reduced ERK1 and ERK2 phosphorylation in the dHip of
equilibrative nucleoside transporter type 1 (ENT1-/-) null mice, which displayed
exacerbated impulsivity. To determine whether impulsive response behavior is
associated with hippocampal neuroblast development, we investigated expression of
BrdU+ and doublecortin (DCX+) following 5-CSRTT testing. These studies revealed
that impulsive behavior driven by inhibition of the A2AR is accompanied by
increased neuroblast proliferation in the hippocampus.
PMID- 28418411
TI - [Groping in the dark: unheard pain 2].
AB - For a very severely mentally disabled, deaf and blind man, it was always very
difficult to carry out dental check-ups, diagnosis and treatment, even with
pharmacologic support. The man cannot communicate pain. When caries and calculus
were diagnosed, the man was treated under general anaesthesia. During this
treatment session he was also found to have severe periodontal disease and peri
apical problems. The legal representative of the patient was unavailable for
consultation on changes to the pre-prepared preliminary treatment plan. This
created a dilemma for the dental treatment team. This case study was presented
during the conference 'State of the art' on March 17, 2017, that was organised by
the Society for the Promotion of Dental Health Care for People with Disabilities
(VBTGG). In this second part of the case, the treatment that was ultimately
chosen is described, considered and discussed.
PMID- 28418413
TI - [How useful is restorative care in the primary dentition?]
AB - Too many children develop carious lesions and many such lesions progress into a
dentine carious lesion. In 2010, the percentage of dentine carious lesions in the
primary dentition of 6-year-old Dutch children that were restored was less than
50 per cent. Owing to research, the necessity to restore dentine carious lesions
routinely has been called into question. Current understanding of cariologic
principles point in the direction of a causal treatment that is based on cleaning
accessible dentine carious cavities and those that can be made accessible,
possibly supported by the application of silver diamine fluoride. The ultimate
goal of a restoration in the primary dentition is to make it possible to remove
biofilm from the tooth surface and to prevent infection of the pulp. If
restoration in primary teeth is necessary, dental practitioners will, in order to
prevent the development of dental anxiety, first have to consider whether it is
feasible to place restorations in an atraumatic manner, for example by means of
the ART method or the Hall technique.
PMID- 28418412
TI - [The family's influence on the oral health of children. A peek behind the front
door].
AB - The prevention of dental caries seems fairly easy. The disease can largely be
avoided by the daily removal of dental plaque using fluoride toothpaste and the
control of sugary intakes. Most parents have sufficient knowledge and motivation
to adhere to this prevention advice with respect to their children. Actual
practice, however, proves quite difficult because parents experience barriers in
implementing the advice. This article provides an overview of the most important
family-related factors that influence children's oral health behaviour and dental
caries experience. Factors include oral health-related attitudes of the parents,
the way that parents deal with their children and communicate with them
(parenting practices) and the organisation of daily life within the family
(family functioning). It's important for oral health care providers to engage in
conversations with parents to identify possible barriers. Tailored advice can
then be given to help them improve their oral health behaviour.
PMID- 28418414
TI - [(Erosive) tooth wear in children and adolescents in the Netherlands: how big is
the problem?]
AB - According to international research, the prevalence of (erosive) tooth wear among
children and adolescents has grown steadily in recent decades. The question was
whether this also applies to the Netherlands and what changes in consumption
patterns may play a role in this development. From 1998 up to and including 2011,
9 studies have been carried out on the prevalence of (erosive) tooth wear among
the young. A meta-analysis of these studies reveals that an increase has also
taken place in the Netherlands. Furthermore, a tendency was found for greater
prevalence with increasing age. It is generally assumed that changes in the
supply of food and drink and therefore consumption patterns have been a major
reason for this increase in children and adolescents. However, longitudinal
studies, in which both the prevalence and incidence of (erosive) tooth wear are
investigated, are needed to support these assumptions. Such studies are, however,
scarce and, moreover, the results show no consistent picture.
PMID- 28418415
TI - [Role of the oral care provider to call attention to child abuse].
AB - The focus on child abuse has increased in recent years. In 2015, the Royal Dutch
Association of Dentists (KNMT) revised the Sign Code 'child abuse and domestic
violence'. The core of the Sign Code is formed by the compulsory 5-step action
plan for the signalling of, among other things, (a suspicion of) child abuse that
must be followed. Dealing professionally with child abuse places high demands on
the knowledge and communication skills of the health care provider. If the
demands are met, the health care provider is by law adequately protected against
complaints. Many health care providers are still uncomfortable about applying the
Sign Code. The number of contacts with Safe at Home for advice and reports coming
from oral care amounts to only a few one-thousandths of the total number of
contacts. In dealing with the neglecting of oral care, the most common form of
child abuse in the area of dental care, professional action is usually still
limited to symptom relief. Organised care via chain formation offers
possibilities for the coordination of targeted action on child abuse.
PMID- 28418416
TI - [Dental treatment of fearful children: subjection, denyal or -guidance?]
AB - Dental treatment anxiety is a common fear among children. The dental health care
provider is faced with difficult dilemmas about ensuring good oral health for
these children in general daily practice. The indicated treatment usually exceeds
the capacity of the frightened child, but when treatment is not performed, the
child is at risk of serious general health problems and its quality of life could
diminish. This article provides an overview of the aetiology of dental treatment
anxiety in children. In addition, the dental practitioner is provided with
insight into the possibilities that allow him/her to enhance the treatability of
the child and reduce anxiety to such an extent that the indicated dental care can
be provided. Psychotherapy and cognitive-behavioural techniques, as well as
pharmacological therapies, are currently considered the most acceptable and
successful treatments for anxiety and phobia. The dental care provider will have
to determine a well-motivated and carefully considered course of treatment,
always keeping in mind the individual context of the child.
PMID- 28418418
TI - Engaging dual donor sites within an N-heterocyclic olefin phosphine ligand.
AB - By investigating the coordination chemistry of a neutral N-heterocyclic olefin
phosphine ligand, a new digold(i) chloride complex was discovered, demonstrating
that mixed element (P/C) donor sites can be accessed at the same time. However
attempts to extend this strategy for the preparation of heterobimetallic
complexes featuring copper(i) and gold(i) centers with this mixed donor ligand
were unsuccessful. The related monometallic copper(i) and gold(i) iodide
complexes were discovered to be emissive in the solid state.
PMID- 28418420
TI - Selective purification and chemical labeling of a target protein on ruthenium
photocatalyst-functionalized affinity beads.
AB - Selective purification and chemical labeling of a target protein in a protein
mixture were simultaneously achieved on the surface of affinity beads
functionalized with ligands, such as benzenesulfonamide and methotrexate (MTX),
and a ruthenium complex containing 2,2'-bipyridine-4,4'-dicarboxylic acid
(dcbpy). Chemical labeling of the target protein with a tyrosine radical trapper
(TRT) proceeded on the surface of the beads when the target protein was in close
proximity to the ruthenium photocatalyst. Both the protein purification and
chemical labeling abilities of the affinity beads functionalized with ruthenium
photocatalyst were not compromised after recycling several times. Dihydrofolate
reductase (DHFR) endogenously expressed in HeLa cells was detected by chemical
labeling with biotin-TRT on the affinity beads with high sensitivity compared to
the conventional silver staining method.
PMID- 28418422
TI - A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice.
AB - Diabetic nephropathy is a major chronic renal complication of diabetes mellitus,
and is the leading cause of end-stage kidney diseases. Establishing a disease
model of diabetic nephropathy in vitro can accelerate the understanding of its
mechanisms and pharmaceutical development. We provide the proof-of-principle for
using a glomerulus-on-a-chip microdevice that reconstitutes organ-level kidney
functions to create a human disease model of early stage diabetic nephropathy on
chip. The microfluidic device, which recapitulates the glomerular
microenvironment, consists of parallel channels lined by isolated primary
glomerular microtissues that experience fluid flow to mimic the glomerular
filtration barrier (GFB), including glomerular endothelial cells, 3D basement
membrane and podocytes. This device was used to reproduce high glucose-induced
critical pathological responses in diabetic nephropathy as observed in humans.
The results reveal that hyperglycemia plays a crucial role in the development of
increased barrier permeability to albumin and glomerular dysfunction that lead to
proteinuria. This organ-on-a-chip microdevice mimics the critical pathological
responses of glomerulus that are characteristic of diabetic nephropathy that has
not been possible by cell-based and animal models, providing a useful platform
for studying the mechanism of diabetic nephropathy and developing an effective
therapy in glomerular diseases.
PMID- 28418429
TI - Chemical constituents, radical scavenging activity and enzyme inhibitory capacity
of fruits from Cotoneaster pannosus Franch.
AB - Cotoneaster pannosus (Rosaceae) is a semievergreen shrub, producing globose dark
red pomes, native to China and widely used as an ornamental plant all over the
world. Despite its extensive cultivation, little information is available on the
chemical composition and biological activities of its fruits. In this work, the
analysis of the chemical composition of C. pannosus fruits, in terms of phenolic
components, carotenoids and ascorbic acid by HPLC/DAD, HPLC/ESI-MS and MS/MS as
well as in terms of macro- and micro-nutrients was performed. The fruits proved
to be a good source of shikimic acid and caffeoylquinic acids, whereas beta
carotene, pelargonidin-3-O glucoside and cyanidin-3,5-rutinoside gave an
important contribution to the color of the fruit. Both the polar and apolar fruit
extracts showed noteworthy radical scavenger activity and inhibitory effects
against monoamine oxidase A (MAO-A), tyrosinase (TYR) and alpha-glucosidase,
making C. pannosus red pomes a promising candidate ingredient in functional foods
and dietary supplements.
PMID- 28418430
TI - WAT-on-a-chip: a physiologically relevant microfluidic system incorporating white
adipose tissue.
AB - Organ-on-a-chip systems possess a promising future as drug screening assays and
as testbeds for disease modeling in the context of both single-organ systems and
multi-organ-chips. Although it comprises approximately one fourth of the body
weight of a healthy human, an organ frequently overlooked in this context is
white adipose tissue (WAT). WAT-on-a-chip systems are required to create safety
profiles of a large number of drugs due to their interactions with adipose tissue
and other organs via paracrine signals, fatty acid release, and drug levels
through sequestration. We report a WAT-on-a-chip system with a footprint of less
than 1 mm2 consisting of a separate media channel and WAT chamber connected via
small micropores. Analogous to the in vivo blood circulation, convective
transport is thereby confined to the vasculature-like structures and the tissues
protected from shear stresses. Numerical and analytical modeling revealed that
the flow rates in the WAT chambers are less than 1/100 of the input flow rate.
Using optimized injection parameters, we were able to inject pre-adipocytes,
which subsequently formed adipose tissue featuring fully functional lipid
metabolism. The physiologically relevant microfluidic environment of the WAT-chip
supported long term culture of the functional adipose tissue for more than two
weeks. Due to its physiological, highly controlled, and computationally
predictable character, the system has the potential to be a powerful tool for the
study of adipose tissue associated diseases such as obesity and type 2 diabetes.
PMID- 28418431
TI - Body burdens, sources and interrelations of selected toxic and essential elements
among the nine Cree First Nations of Eeyou Istchee, James Bay region of northern
Quebec, Canada.
AB - BACKGROUND: this article constitutes a report on the comprehensive
Nituuchischaayihtitaau Aschii multi-community environment-and-health study
conducted among the Cree peoples (Eeyouch) of northern Quebec, Canada.
OBJECTIVES: to interpret observed concentrations of a suite of chemical elements
in a multi-media biological monitoring study in terms of sources and predictors.
METHODS: the concentrations of 5 essential and 6 toxic chemical elements were
measured in whole blood, and/or in urine or hair by ICP-MS. Concentrations of
essential elements are compared to those considered normal (i.e., required for
good health) and, when toxic, deemed acceptable at specified concentrations in
public health guidelines. Their dependence on age, sex, the specific community
lived-in and diet were explored employing multivariate analysis of variance
(MANOVA) involving new variables generated by principle component analysis (PCA)
and correspondence analysis (CA). RESULTS: the 5 most prominent PCA axes
explained 67.7% of the variation, compared to 93.0% by 6 main CA factors.
Concentrations of the essential elements in whole blood (WB) and iodine(i) and
arsenic (As) in urine were comparable to those reported in the recent Canadian
Health Measures survey and are assigned to dietary sources. By contrast, WB
cadmium (Cd) was elevated even when smoking was considered. Mercury (Hg)
concentrations in WB and hair were also higher in adults, although comparable to
those observed for other indigenous populations living at northern latitudes.
Fish consumption was identified as the prominent source. Of the 5 coastal
communities, all but one had lower Hg exposures than the four inland communities,
presumably reflecting the type of fish consumed. Use of firearms and smoking were
correlated with WB-lead (Pb). The concentrations of both Hg and Pb increased with
age and were higher in men, while WB-Cd and smoking prevalence were higher in
women when considering all communities. Hg and Pb were low in children and women
of reproductive age, with few exceedances of health guidelines. Although
individuals with T2D had somewhat lower WB-Cd, there is some indication that Cd
may potentiate renal dysfunction in this subgroup. Plots of selected CA axes
grouped those elements expected to be in a normal diet and distinguished them
from those with well-known unique sources (especially Hg and As in hair; and Hg,
Pb and Cd in WB). CONCLUSIONS: the use of multiple biological media in
conjunction with the complementary PCA and CA approaches for constructing
composite variables allowed a more detailed understanding of both the sources of
the essential and toxic elements in body fluids and the dependencies of their
observed concentrations on age, sex, community and diet.
PMID- 28418433
TI - Capsaicin presynaptically inhibits glutamate release through the activation of
TRPV1 and calcineurin in the hippocampus of rats.
AB - Capsaicin is the major ingredient in hot peppers of the plant Capsicum genus with
neuroprotective effects in several preclinical models; its effect on glutamate
release has been investigated in the rat hippocampus using isolated nerve
terminals (synaptosomes) and brain slices. In a synaptosomal preparation,
capsaicin dose-dependently reduced 4-aminopyridine-evoked Ca2+-dependent
glutamate release, with an IC50 of approximately 11 MUM. This inhibition was
blocked by capsazepin, an antagonist of TRPV1, which was found to be colocalized
with the vesicle marker protein synaptophysin in synaptosomes using double
immunostaining. Capsaicin decreased 4-aminopyridine-evoked intrasynaptosomal Ca2+
concentration elevation and the capsaicin-mediated inhibition of glutamate
release was prevented by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel
blocker omega-conotoxin MVIIC, but was not affected by the intracellular Ca2+
release inhibitors dantrolene and CGP37157. Furthermore, capsaicin increased the
4-aminopyridine-induced phosphorylation of protein phosphatase calcineurin and
the calcineurin inhibitor cyclosporine A eliminated the inhibitory effect of
capsaicin on evoked glutamate release. Additionally, capsaicin also reduced the
frequency of miniature excitatory postsynaptic currents without affecting their
amplitude in slice preparations. Together, these results suggest that capsaicin
acts at TRPV1 present on hippocampal nerve terminals to increase calcineurin
activation, which subsequently attenuates voltage-dependent Ca2+ entry to cause a
decrease in evoked glutamate release.
PMID- 28418435
TI - Fullerenes for catalysis: metallofullerenes in hydrogen transfer reactions.
AB - [60]Fullerene hybrids have successfully been used as catalysts in hydrogen
transfer reactions, namely ketone reduction and N-alkylation with alcohols. Due
to their poor solubility in polar solvents, these hybrids behave as
homogeneous/heterogeneous catalysts that can be mechanically separated and reused
several times while the final products do not need chromatographic separation.
PMID- 28418439
TI - Non-symmetrical, potentially redox non-innocent imino NHC pyridine 'pincers' via
a zinc ion template-assisted synthesis.
AB - New non-symmetrical, redox-active imino NHC pyridine pincer ligands, 2-(R1
imidazol-2-ylidene)-6-(R2N[double bond, length as m-dash]CH)-pyridine (R1 = 2,6
diisopropylphenyl (DiPP), R2 = 2,4,6-trimethylphenyl (Mes), 4B; R1 = R2 = DiPP,
4C), have been accessed by a ZnII-promoted modular synthesis involving the
quaternization of R1-imidazole by [Zn(kappaNiminekappaNpyridine)(2-(R2N[double
bond, length as m-dash]CH)-6-bromo-pyridine)Cl2], followed by ZnII removal and
deprotonation of imidazolium pro-ligands. Redox active forms of 4B were
implicated in the two complexes obtained by its reaction with FeBr2/KC8; metrical
data analysis pointed to the occurrence of radical anionic and dianionic redox
states of 4B.
PMID- 28418438
TI - A scalable self-priming fractal branching microchannel net chip for digital PCR.
AB - As an absolute quantification method at the single-molecule level, digital PCR
has been widely used in many bioresearch fields, such as next generation
sequencing, single cell analysis, gene editing detection and so on. However,
existing digital PCR methods still have some disadvantages, including high cost,
sample loss, and complicated operation. In this work, we develop an exquisite
scalable self-priming fractal branching microchannel net digital PCR chip. This
chip with a special design inspired by natural fractal-tree systems has an even
distribution and 100% compartmentalization of the sample without any sample loss,
which is not available in existing chip-based digital PCR methods. A special 10
nm nano-waterproof layer was created to prevent the solution from evaporating. A
vacuum pre-packaging method called self-priming reagent introduction is used to
passively drive the reagent flow into the microchannel nets, so that this chip
can realize sequential reagent loading and isolation within a couple of minutes,
which is very suitable for point-of-care detection. When the number of positive
microwells stays in the range of 100 to 4000, the relative uncertainty is below
5%, which means that one panel can detect an average of 101 to 15 374 molecules
by the Poisson distribution. This chip is proved to have an excellent ability for
single molecule detection and quantification of low expression of hHF-MSC stem
cell markers. Due to its potential for high throughput, high density, low cost,
lack of sample and reagent loss, self-priming even compartmentalization and
simple operation, we envision that this device will significantly expand and
extend the application range of digital PCR involving rare samples, liquid biopsy
detection and point-of-care detection with higher sensitivity and accuracy.
PMID- 28418440
TI - An all-atom molecular dynamics study of the anti-interferon signaling of Ebola
virus: interaction mechanisms of EBOV VP24 binding to Karyopherin alpha5.
AB - Ebola virus (EBOV) is highly lethal due to virally encoded immune antagonists,
and the combination of EBOV VP24 with karyopherin alpha (KPNA) will trigger anti
interferon (IFN) signaling. The crystal structure of VP24-KPNA5 has been proposed
in recent studies, but the precise binding mechanisms are still unclear. In order
to explore the VP24-KPNA5 protein binding micro-mechanisms, Molecular Dynamic
(MD) simulations and Molecular Mechanics Generalized Born Surface Area (MM-GB/SA)
energy calculation are performed. The obtained results show that EBOV VP24
binding to KPNA5 will rigidify their binding-face, and both proteins will be
compacted during binding. According to the analyses of binding free energies of
WT and the eight mutant systems, MUT3 makes the most effective contributions to
the interaction; additionally MUT4, R398A and the double mutant have the second
most effective influence. Hydrogen bond analysis demonstrates that inhibitors
which can interfere with the formation of hydrogen bonds D480-T138, E483-R137 and
D205-R396 will prevent the anti-IFN effect. Meanwhile, by combining the
decomposition of binding free energies (DC) with computational alanine scanning
(CAS) results, it is shown that VP24 residues R137 and T138 will be potential
targets for EBOV VP24 inhibitors, and KPNA5 residues R396, R398, R480, Y477 and
F484 will be potential targets to prevent KPNA5 binding to VP24, which will
ultimately block anti-IFN signaling. Our investigations provide theoretical data
to understand the binding modes of VP24-KPNA5. The precise binding mechanisms of
the complex may shed light on the development of potential novel inhibitors
against EBOV infection.
PMID- 28418441
TI - An integrated anti-arrhythmic target network of a Chinese medicine compound,
Wenxin Keli, revealed by combined machine learning and molecular pathway
analysis.
AB - Wenxin Keli (WK), a Chinese patent medicine, is known to be effective against
cardiac arrhythmias and heart failure. Although a number of electrophysiological
findings regarding its therapeutic effect have been reported, the active
components and system-level characterizations of the component-target
interactions of WK have yet to be elucidated. In the current study, we present
the first report of a new protective effect of WK on suppressing anti-arrhythmic
agent-induced arrhythmias. In a model of isolated guinea pig hearts, rapid
perfusion of quinidine altered the heart rate and prolonged the Q-T interval.
Pretreatment with WK significantly prevented quinidine-induced arrhythmias. To
explain the therapeutic and protective effects of WK, we constructed an
integrated multi-target pharmacological mechanism prediction workflow in
combination with machine learning and molecular pathway analysis. This workflow
had the ability to predict and rank the probability of each compound interacting
with 1715 target proteins simultaneously. The ROC value statistics showed that
97.786% of the values for target prediction were larger than 0.8. We applied this
model to carry out target prediction and network analysis for the identified
components of 5 herbs in WK. Using the 124 potential anti-arrhythmic components
and the 30 corresponding protein targets obtained, an integrative anti-arrhythmic
molecular mechanism of WK was proposed. Emerging drug/target networks suggested
ion channel and intracellular calcium and autonomic nervous and hormonal
regulation had critical roles in WK-mediated anti-arrhythmic activity. A
validation of the proposed mechanisms was achieved by demonstrating that calaxin,
one of the WK components from Gansong, dose-dependently blocked its predicted
target CaV1.2 channel in an electrophysiological assay.
PMID- 28418442
TI - Network analysis and percolation transition in hydrogen bonded clusters: nitric
acid and water extracted by tributyl phosphate.
AB - Extraction of polar molecules by amphiphilic species results in a complex variety
of clusters whose topologies and energetics control phase behavior and efficiency
of liquid-liquid separations. A computational approach including quantum
mechanical vibrational frequency calculations and molecular dynamics simulation
with intermolecular network theory is used to provide a robust assessment of
extractant and polar solute association through hydrogen bonding in the tributyl
phosphate (TBP)/HNO3/H2O/dodecane system for the first time. The distribution of
local topologies of the TBP/HNO3/H2O hydrogen bonded clusters is shown to be
consistent with an equilibrium binding model. Mixed TBP/HNO3/H2O clusters are
predicted that have not been previously observable in experiment due to
limitations in scattering and spectroscopic resolution. Vibrational frequency
calculations are compared with experimental data to validate the experimentally
observed TBP-HNO3-HNO3 Chain structure. At high nitric acid and water loading,
large hydrogen-bonded clusters of 20 to 80 polar solutes formed. The cluster
sizes were found to be exponentially distributed, consistent with a constant
average solute association free energy in that size range. Due to the deficit of
hydrogen bond donors in the predominantly TBP/HNO3 organic phase, increased water
concentrations lower the association free energy and enable growth of larger
cluster sizes. For sufficiently high water concentrations, changes in the cluster
size distribution are found to be consistent with the formation of a percolating
cluster rather than reverse micelles, as has been commonly assumed for the
occurrence of an extractant-rich third phase in metal-free solvent extraction
systems. Moreover, the compositions of the large clusters leading to percolation
agrees with the 1 : 3 TBP : HNO3 ratio reported in the experimental literature
for TBP/HNO3/H2O third phases. More generally, the network analysis of cluster
formation from atomic level interactions could allow for control of phase
behavior in multi-component solutions of species with a variety of hydrogen bond
types.
PMID- 28418443
TI - Inaugural Symposium on Advanced Surgical Techniques in Adult Airway
Reconstruction: Proceedings of the North American Airway Collaborative (NoAAC).
PMID- 28418445
TI - Decision Making in Adrenoleukodystrophy: When Is a Good Outcome Really a Good
Outcome?
PMID- 28418446
TI - Anticoagulation Reversal for Supratherapeutic International Normalized Ratio: A
Teachable Moment.
PMID- 28418444
TI - Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer.
AB - Importance: Germline pathogenic variants in BRCA1 and BRCA2 predispose to an
increased lifetime risk of breast cancer. However, the relevance of germline
variants in other genes from multigene hereditary cancer testing panels is not
well defined. Objective: To determine the risks of breast cancer associated with
germline variants in cancer predisposition genes. Design, Setting, and
Participants: A study population of 65 057 patients with breast cancer receiving
germline genetic testing of cancer predisposition genes with hereditary cancer
multigene panels. Associations between pathogenic variants in non-BRCA1 and non
BRCA2 predisposition genes and breast cancer risk were estimated in a case
control analysis of patients with breast cancer and Exome Aggregation Consortium
reference controls. The women underwent testing between March 15, 2012, and June
30, 2016. Main Outcomes and Measures: Breast cancer risk conferred by pathogenic
variants in non-BRCA1 and non-BRCA2 predisposition genes. Results: The mean (SD)
age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1)
years. The frequency of pathogenic variants in 21 panel genes identified in 41
611 consecutively tested white women with breast cancer was estimated at 10.2%.
After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN,
and TP53), observed pathogenic variants in 5 of 16 genes were associated with
high or moderately increased risks of breast cancer: ATM (OR, 2.78; 95% CI, 2.22
3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67),
PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88).
Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the
MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair
genes; and NF1 were not associated with increased risks of breast cancer.
Conclusions and Relevance: This study establishes several panel genes as high-
and moderate-risk breast cancer genes and provides estimates of breast cancer
risk associated with pathogenic variants in these genes among individuals
qualifying for clinical genetic testing.
PMID- 28418448
TI - beta-Blocker Exposure in Pregnancy and Risk of Fetal Cardiac Anomalies.
PMID- 28418447
TI - Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain
Fluid With Patient Outcomes.
AB - Importance: Survival rates for head and neck cancer have been relatively stable
for several decades. Individualized prognostic indicators are needed to identify
patients at risk for poorer outcomes. Objective: To determine whether biomarker
levels in surgical drain fluid of patients with head and neck cancer are
associated with poor cancer outcomes. Design, Setting, and Participants: This
prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of
the oral cavity and oropharynx who required surgical treatment from April 1,
2011, to February 1, 2016, at a tertiary or academic care center. Twenty
patients, including 14 with stage IV disease, had complete specimen collection.
Differences in cytokine and MMP levels by disease outcomes were evaluated.
Interventions: Patients underwent surgical treatment with drain placement as
dictated by the standard of care. Drain fluid samples were collected every 8
hours postoperatively until drains were removed because of clinical criteria.
Levels of cytokines and matrix metalloproteinases (MMPs) were measured using
electrochemiluminescent, patterned array, multiplex technology. Main Outcomes and
Measures: The primary clinical outcome measures were survival outcome and
recurrence. The biomarkers measured included the cytokines basic fibroblastic
growth factor, vascular endothelial growth factor isoform A, soluble fms-like
tyrosine kinase-1 (sFlt-1), and placental growth factor (PIGF) and MMP-1, MMP-3,
and MMP-9. Other clinical and pathologic cancer characteristics were recorded.
Results: In this cohort of 20 patients with SCC (15 men and 5 women; mean [SD]
age, 63.5 [9.9] years), a significant association with recurrence was found for
levels of MMP-1 (relative difference between groups, 2.78; 95% CI, 1.23-6.29),
MMP-3 (relative difference between groups, 5.29; 95% CI, 2.14-13.05), and sFlt-1
(relative difference between groups, 3.75; 95% CI, 1.84-7.65). No biomarkers were
associated with disease outcome. Vascular endothelial growth factor isoform A was
associated with nodal metastasis (relative difference between groups, 1.98; 95%
CI, 1.12-3.51), and basic fibroblastic growth factor was associated with
lymphovascular invasion (relative difference between groups, 1.74; 95% CI, 1.02
2.97). Conclusions and Relevance: In this pilot sample of patients with SCC of
the oral cavity and oropharynx, MMP-1, MMP-3, and sFlt-1 levels in wound fluid
were associated with poor clinical cancer outcomes in the form of recurrence.
This finding is consistent with the literature of tumor microenvironment in
saliva, serum, and tumor tissue biomarkers. To our knowledge, this report is the
first of such findings in surgical drain fluid, an easily accessible means of
cytokine measurement. Measurement of these biomarkers in surgical fluid
potentially represents a novel means of assessing cancer prognosis in this
population.
PMID- 28418449
TI - Association of a Communication Training Program With Use of Antipsychotics in
Nursing Homes.
AB - Importance: Off-label antipsychotic prescribing in nursing homes (NHs) is common
and is associated with increased risk of mortality in older adults. Prior large
scale, controlled trials in the NH setting failed to show meaningful reductions
in antipsychotic use. Objective: To quantify the influence of a large-scale
communication training program on NH antipsychotic use called OASIS. Design,
Setting, and Participants: This investigation was a quasi-experimental
longitudinal study of NHs in Massachusetts enrolled in the OASIS intervention.
Participants were residents living in NHs between March 1, 2011, and August 31,
2013. The data were analyzed from December 2015, to March 2016, and from November
through December 2016. Exposures: The OASIS educational program targets all NH
staff (direct care and nondirect care) using a train-the-trainer model. The
program goals were to reframe challenging behaviors of residents with cognitive
impairment as the communication of unmet needs, to train staff to anticipate
resident needs, and to integrate resident strengths into daily care plans. Main
Outcomes and Measures: This study used an interrupted time series model of
facility-level prevalence of antipsychotic medication use, other psychotropic
medication use (antidepressants, anxiolytics, and hypnotics), and behavioral
disturbances to evaluate the intervention's effectiveness in participating
facilities compared with control NHs in Massachusetts and New York. The 18-month
preintervention (baseline) period was compared with a 3-month training period, a
6-month implementation period, and a 3-month maintenance period. Results: This
study included 93 NHs enrolled in the OASIS intervention (27 of which had a high
prevalence of antipsychotic use) compared with 831 nonintervention NHs. Among
OASIS facilities, prevalences of atypical antipsychotic prescribing were 34.1% at
baseline and 26.5% at the study end (absolute reduction of 7.6% and relative
reduction of 22.3%) compared with a drop of 22.7% to 18.8% in the comparison
facilities (absolute reduction of 3.9% and relative reduction of 17.2%). In the
OASIS implementation phase, NHs experienced a reduction in antipsychotic use
prevalence among OASIS facilities (-1.20%; 95% CI, -1.85% to -0.09% per quarter)
greater than that among non-OASIS facilities (-0.23%; 95% CI, -0.47% to 0.01% per
quarter), resulting in a net OASIS influence of -0.97% (95% CI, -1.85% to -0.09%;
P = .03). A difference in trend was not sustained in the maintenance phase
(difference of 0.93%; 95% CI, -0.66% to 2.54%; P = .48). No increases in other
psychotropic medication use or behavioral disturbances were observed. Conclusions
and Relevance: Antipsychotic use prevalence declined during OASIS implementation
of the intervention, but the decreases did not continue in the maintenance phase.
Other psychotropic medication use and behavioral disturbances did not increase.
This study adds evidence for nonpharmacological programs to treat behavioral and
psychological symptoms of dementia.
PMID- 28418450
TI - The Draw(backs) of Big Data.
PMID- 28418452
TI - Multigene Panel Testing and Breast Cancer Risk: Is It Time to Scale Down?
PMID- 28418453
TI - Association of Increasing Nasal Tip Projection With Lip Position in Primary
Rhinoplasty.
AB - Importance: The effects of rhinoplasty maneuvers on adjacent facial features are
an important component in preoperative planning and patient counseling. Tip
projection modifications are commonly performed in both cosmetic and
reconstructive rhinoplasty. Objective: To evaluate the subsequent change in lip
projection that results from increasing nasal tip projection. Design, Setting,
and Participants: In this case series, 20 patients underwent primary rhinoplasty
with the objective of increasing tip projection during the period from October 1,
2014, to September 25, 2015. Preoperative and postoperative photographs were
evaluated. Main Outcomes and Measures: The increased tip projection was verified
using the Goode ratio. Upper lip projection was calculated by the Z angle, which
is based on the intersection between the Frankfort horizontal plane and the
profile line. Vermilion height was also assessed. Results: Of the 20 patients in
the study (19 females and 1 male; mean [SD] age, 26.8 [10.2] years; range, 16-52
years) 18 (90%) demonstrated an increase in upper lip projection when the tip
projection was increased by either a columellar strut or tongue-in-groove
maneuver. The Z angle demonstrated a statistically significant decrease of 2.7
degrees (95% CI, 1.5 degrees -3.9 degrees ; P < .001). Although the vermilion
height did not change a significant amount, there was a trend toward an increase
in mean height of 0.051 (95% CI, -0.00515 to -0.10685; P = .09). Conclusions and
Relevance: Increasing nasal tip projection causes a measurable increase in upper
lip projection. This new causal association has been applied to our filler
injection armamentarium as an alternative way to achieve the desired result of a
more youthful upper lip. Level of Evidence: 4.
PMID- 28418451
TI - Cost-effectiveness of Common Diagnostic Approaches for Evaluation of Asymptomatic
Microscopic Hematuria.
AB - Importance: Asymptomatic microscopic hematuria (AMH) is highly prevalent and may
signal occult genitourinary (GU) malignant abnormality. Common diagnostic
approaches differ in their costs and effectiveness in detecting cancer. Given the
low prevalence of GU malignant abnormality among patients with AMH, it is
important to quantify the cost implications of detecting cancer for each
approach. Objective: To estimate the effectiveness, costs, and incremental cost
per cancer detected (ICCD) for 4 common diagnostic approaches evaluating AMH.
Design, Setting, and Participants: A decision-analytic model-based cost
effectiveness analysis using inputs from the medical literature. PubMed searches
were performed to identify relevant literature for all key model inputs, each of
which was derived from the clinical study with the most robust data and greatest
applicability. Analysis included adult patients with AMH on routine urinalysis
with subgroups of high-risk patients (males, smokers, age >=50 years) seen in the
primary care or urologic referral setting. Interventions: Four diagnostic
approaches were evaluated relative to the reference case of no evaluation: (1)
computed tomography (CT) alone; (2) cystoscopy alone; (3) CT and cystoscopy
combined; and (4) renal ultrasound and cystoscopy combined. Main Outcomes and
Measures: At termination of the diagnostic period, cancers detected, costs (payer
perspective), and ICCD per 10 000 patients evaluated for AMH. Results: Of the 4
diagnostic approaches analyzed, CT alone was dominated by all other strategies,
detecting 221 cancers at a cost of $9 300 000. Ultrasound and cystoscopy detected
245 cancers and was most cost-effective with an ICCD of $53 810. Replacing
ultrasound with CT detected just 1 additional cancer at an ICCD of $6 480 484.
Ultrasound and cystoscopy remained the most cost-effective approach in subgroup
analysis. The model was not sensitive to any inputs within the proposed ranges.
Using probabilistic sensitivity analysis, ultrasound and cystoscopy was the
dominant strategy in 100% of simulations. Conclusions and Relevance: The
combination of renal ultrasound and cystoscopy is the most cost-effective among 4
diagnostic approaches for the initial evaluation of AMH. The use of ultrasound in
lieu of CT as the first-line diagnostic strategy will optimize cancer detection
and reduce costs associated with evaluation of AMH. Given our findings, we need
to critically evaluate the appropriateness of our current clinical practices, and
potentially alter our guidelines to reflect the most effective screening
strategies for patients with AMH.
PMID- 28418454
TI - An Indirect Indentation Method for Evaluating the Linear Viscoelastic Properties
of the Brain Tissue.
AB - Indentation experiments offer a robust, fast, and repeatable testing method for
evaluating the mechanical properties of the solid-state materials in a wide
stiffness range. With the advantage of requiring a minimal sample preparation and
multiple tests on a small piece of specimen, this method has recently become a
popular technique for measuring the elastic properties of the biological
materials, especially the brain tissue whose ultrasoft nature makes its
mechanical characterization very challenging. Nevertheless, some limitations are
associated with the indentation of the brain tissue, such as improper surface
detection, negative initial contact force due to tip-tissue moisture interaction,
and partial contact between the tip and the sample. In this study, an indirect
indentation scheme is proposed to overcome the aforementioned difficulties. In
this way, the indentation force is transferred from a sharp tip to the surface of
the tissue slices via a rigid coverslip. To demonstrate the accuracy of this
method, the linear viscoelastic properties of the white and gray matters of the
bovine brain samples are measured by imposing small cyclic loads at different
frequencies. The rate, regional, directional, and postmortem time dependence of
the viscoelastic moduli are investigated and compared with the previous results
from cyclic shear and monotonic experiments on the brain tissue. While findings
of this research present a comprehensive set of information for the viscoelastic
properties of the brain at a wide frequency range, the central goal of this paper
is to introduce a novel experimentation technique with noticeable advantages for
biomechanical characterization of the soft tissue.
PMID- 28418455
TI - The Development and Performance of After-Hours Primary Care in the Netherlands: A
Narrative Review.
AB - In many Western countries, hospital emergency departments are overcrowded,
leading to the desire to strengthen primary care, particularly after hours. To
achieve this goal, an increasing number of Western nations are reorganizing their
after-hours primary care systems into large-scale primary care physician (PCP)
cooperatives. This article provides an overview of the organization, performance,
and development of PCP cooperatives in the Netherlands. The Dutch after-hours
primary care system might offer opportunities for other countries facing problems
with after-hours care and inappropriate emergency department visits. During the
past several years, the number of contacts with Dutch PCP cooperatives has
increased to 245 contacts per 1000 citizens per year. Many contacts (45%) are
nonurgent, and about half occur as part of a series of primary care contacts. Low
accessibility and availability of daytime primary care are related to greater use
of after-hours primary care. To prevent unnecessary attendance at the
cooperatives, physicians advocate copayment, a stricter triage system, and a
larger role for telephone doctors. More than half of the PCP cooperatives in the
Netherlands have integrated with hospital emergency departments, forming
"emergency care access points." This collaboration has decreased emergency
department use by 13% to 22%, and treatment of self-referrals by PCP cooperatives
in emergency care access points is safe and cost-effective. Direct access to
diagnostic facilities may optimize efficiency even more. Other recent
developments include access to electronic health records of daytime primary care
practices, task substitution from physicians to nurses, and the launch of a 2
year training program for PCPs to become experts in emergency care.
PMID- 28418457
TI - The field of view available to the ventral occipito-temporal reading circuitry.
AB - Skilled reading requires rapidly recognizing letters and word forms; people learn
this skill best for words presented in the central visual field. Measurements
over the last decade have shown that when children learn to read, responses
within ventral occipito-temporal cortex (VOT) become increasingly selective to
word forms. We call these regions the VOT reading circuitry (VOTRC). The portion
of the visual field that evokes a response in the VOTRC is called the field of
view (FOV). We measured the FOV of the VOTRC and found that it is a small subset
of the entire field of view available to the human visual system. For the typical
subject, the FOV of the VOTRC in each hemisphere is contralaterally and foveally
biased. The FOV of the left VOTRC extends ~9 degrees into the right visual field
and ~4 degrees into the left visual field along the horizontal meridian. The FOV
of the right VOTRC is roughly mirror symmetric to that of the left VOTRC. The
size and shape of the FOV covers the region of the visual field that contains
relevant information for reading English. It may be that the size and shape of
the FOV, which varies between subjects, will prove useful in predicting
behavioral aspects of reading.
PMID- 28418456
TI - Mapping the Early Language Environment Using All-Day Recordings and Automated
Analysis.
AB - Purpose: This research provided a first-generation standardization of automated
language environment estimates, validated these estimates against standard
language assessments, and extended on previous research reporting language
behavior differences across socioeconomic groups. Method: Typically developing
children between 2 to 48 months of age completed monthly, daylong recordings in
their natural language environments over a span of approximately 6-38 months. The
resulting data set contained 3,213 12-hr recordings automatically analyzed by
using the Language Environment Analysis (LENA) System to generate estimates of
(a) the number of adult words in the child's environment, (b) the amount of
caregiver-child interaction, and (c) the frequency of child vocal output.
Results: Child vocalization frequency and turn-taking increased with age, whereas
adult word counts were age independent after early infancy. Child vocalization
and conversational turn estimates predicted 7%-16% of the variance observed in
child language assessment scores. Lower socioeconomic status (SES) children
produced fewer vocalizations, engaged in fewer adult-child interactions, and were
exposed to fewer daily adult words compared with their higher socioeconomic
status peers, but within-group variability was high. Conclusions: The results
offer new insight into the landscape of the early language environment, with
clinical implications for identification of children at-risk for impoverished
language environments.
PMID- 28418459
TI - Distribution of Physicians With H-1B Visas By State and Sponsoring Employer.
PMID- 28418460
TI - Marijuana Use During Stages of Pregnancy in the United States.
PMID- 28418458
TI - Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure
Overload: A Computational Study.
AB - Right ventricular failure (RVF) is a lethal condition in diverse pathologies.
Pressure overload is the most common etiology of RVF, but our understanding of
the tissue structure remodeling and other biomechanical factors involved in RVF
is limited. Some remodeling patterns are interpreted as compensatory mechanisms
including myocyte hypertrophy, extracellular fibrosis, and changes in fiber
orientation. However, the specific implications of these changes, especially in
relation to clinically observable measurements, are difficult to investigate
experimentally. In this computational study, we hypothesized that, with other
variables constant, fiber orientation alteration provides a quantifiable and
distinct compensatory mechanism during RV pressure overload (RVPO). Numerical
models were constructed using a rabbit model of chronic pressure overload RVF
based on intraventricular pressure measurements, CINE magnetic resonance imaging
(MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were
conducted under normotensive and hypertensive boundary conditions using
variations in RV wall thickness, tissue stiffness, and fiber orientation to
investigate their effect on RV pump function. Our results show that a
longitudinally aligned myocardial fiber orientation contributed to an increase in
RV ejection fraction (RVEF). This effect was more pronounced in response to
pressure overload. Likewise, models with longitudinally aligned fiber orientation
required a lesser contractility for maintaining a target RVEF against elevated
pressures. In addition to increased wall thickness and material stiffness
(diastolic compensation), systolic mechanisms in the forms of myocardial fiber
realignment and changes in contractility are likely involved in the overall
compensatory responses to pressure overload.
PMID- 28418461
TI - Look. Listen. Receive.: Surrendering to the Art.
PMID- 28418462
TI - Woman With Yellow Palms and Soles.
PMID- 28418463
TI - Errors in Study Group Numbers and Outcome Interpretation.
PMID- 28418465
TI - Nocturnal Polyuria Drug Approved.
PMID- 28418464
TI - Disentangling Maternal Depression and Antidepressant Use During Pregnancy as
Risks for Autism in Children.
PMID- 28418466
TI - Relief for Dust Mite Allergy.
PMID- 28418467
TI - US-EU Drug Inspection Agreement.
PMID- 28418468
TI - Association Between Maternal Use of SSRI Medications and Autism in Their
Children.
PMID- 28418469
TI - Management of Helicobacter pylori Infection.
PMID- 28418471
TI - Why Replacing the ACA Has Republicans in a Tizzy.
PMID- 28418472
TI - The Medical Expert.
PMID- 28418473
TI - Diagnosis of Bacterial Infection Using a 2-Transcript Host RNA Signature in
Febrile Infants 60 Days or Younger.
PMID- 28418474
TI - Comparative Trends in Payment Adjustments Between Safety-Net and Other Hospitals
Since the Introduction of the Hospital Readmission Reduction Program and Value
Based Purchasing.
PMID- 28418475
TI - Changes in Rates of Ventilator-Associated Pneumonia.
PMID- 28418476
TI - Factors Contributing to the Weekend Effect.
PMID- 28418477
TI - Changes in Rates of Ventilator-Associated Pneumonia-Reply.
PMID- 28418478
TI - Factors Contributing to the Weekend Effect.
PMID- 28418479
TI - Associations of Maternal Antidepressant Use During the First Trimester of
Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum
Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring.
AB - Importance: Prenatal antidepressant exposure has been associated with adverse
outcomes. Previous studies, however, may not have adequately accounted for
confounding. Objective: To evaluate alternative hypotheses for associations
between first-trimester antidepressant exposure and birth and neurodevelopmental
problems. Design, Setting, and Participants: This retrospective cohort study
included Swedish offspring born between 1996 and 2012 and followed up through
2013 or censored by death or emigration. Analyses controlling for pregnancy,
maternal and paternal covariates, as well as sibling comparisons, timing of
exposure comparisons, and paternal comparisons, were used to examine the
associations. Exposures: Maternal self-reported first-trimester antidepressant
use and first-trimester antidepressant dispensations. Main Outcomes and Measures:
Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2
SDs below the mean for gestational age), and first inpatient or outpatient
clinical diagnosis of autism spectrum disorder and attention
deficit/hyperactivity disorder in offspring. Results: Among 1 580 629 offspring
(mean gestational age, 279 days; 48.6% female; 1.4% [n = 22 544] with maternal
first-trimester self-reported antidepressant use) born to 943 776 mothers (mean
age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring
were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational
age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum
disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were
diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the
population level, first-trimester exposure was associated with all outcomes
compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI,
1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism
spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention
deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models
that compared siblings while adjusting for pregnancy, maternal, and paternal
traits, first-trimester antidepressant exposure was associated with preterm birth
(OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01
[95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or
attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results
from analyses assessing associations with maternal dispensations before pregnancy
and with paternal first-trimester dispensations were consistent with findings
from the sibling comparisons. Conclusions and Relevance: Among offspring born in
Sweden, after accounting for confounding factors, first-trimester exposure to
antidepressants, compared with no exposure, was associated with a small increased
risk of preterm birth but no increased risk of small for gestational age, autism
spectrum disorder, or attention-deficit/hyperactivity disorder.
PMID- 28418480
TI - Association Between Serotonergic Antidepressant Use During Pregnancy and Autism
Spectrum Disorder in Children.
AB - Importance: Previous observations of a higher risk of child autism spectrum
disorder with serotonergic antidepressant exposure during pregnancy may have been
confounded. Objective: To evaluate the association between serotonergic
antidepressant exposure during pregnancy and child autism spectrum disorder.
Design, Setting, and Participants: Retrospective cohort study. Health
administrative data sets were used to study children born to mothers who were
receiving public prescription drug coverage during pregnancy in Ontario, Canada,
from 2002-2010, reflecting 4.2% of births. Children were followed up until March
31, 2014. Exposures: Serotonergic antidepressant exposure was defined as 2 or
more consecutive maternal prescriptions for a selective serotonin or serotonin
norepinephrine reuptake inhibitor between conception and delivery. Main Outcomes
and Measures: Child autism spectrum disorder identified after the age of 2 years.
Exposure group differences were addressed by inverse probability of treatment
weighting based on derived high-dimensional propensity scores (computerized
algorithm used to select a large number of potential confounders) and by
comparing exposed children with unexposed siblings. Results: There were 35 906
singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean
maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In
the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%)
of children were diagnosed with autism spectrum disorder. The incidence of autism
spectrum disorder was 4.51 per 1000 person-years among children exposed to
antidepressants vs 2.03 per 1000 person-years among unexposed children (between
group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio
[HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After
inverse probability of treatment weighting based on the high-dimensional
propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997
2.59]). The association was also not significant when exposed children were
compared with unexposed siblings (incidence of autism spectrum disorder was 3.40
per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR,
1.60 [95% CI, 0.69-3.74]). Conclusions and Relevance: In children born to mothers
receiving public drug coverage in Ontario, Canada, in utero serotonergic
antidepressant exposure compared with no exposure was not associated with autism
spectrum disorder in the child. Although a causal relationship cannot be ruled
out, the previously observed association may be explained by other factors.
PMID- 28418481
TI - Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based
on the US Preventive Services Task Force Recommendations vs the ACC/AHA
Guidelines.
AB - Importance: There are important differences among guideline recommendations for
using statin therapy in primary prevention. New recommendations from the US
Preventive Services Task Force (USPSTF) emphasize therapy based on the presence
of 1 or more cardiovascular disease (CVD) risk factors and a 10-year global CVD
risk of 10% or greater. Objective: To determine the difference in eligibility for
primary prevention statin treatment among US adults, assuming full application of
USPSTF recommendations compared with the American College of Cardiology/American
Heart Association (ACC/AHA) guidelines. Design, Setting, and Participants:
National Health and Nutrition Examination Survey (NHANES) data (2009-2014) were
used to assess statin eligibility under the 2016 USPSTF recommendations vs the
2013 ACC/AHA cholesterol guidelines among a nationally representative sample of
3416 US adults aged 40 to 75 years with fasting lipid data and triglyceride
levels of 400 mg/dL or less, without prior CVD. Exposures: The 2016 USPSTF
recommendations vs 2013 ACC/AHA guidelines. Main Outcomes and Measures:
Eligibility for primary prevention statin therapy. Results: Among the US primary
prevention population represented by 3416 individuals in NHANES, the median
weighted age was 53 years (interquartile range, 46-61), and 53% (95% CI, 52%-55%)
were women. Along with the 21.5% (95% CI, 19.3%-23.7%) of patients who reported
currently taking lipid-lowering medication, full implementation of the USPSTF
recommendations would be associated with initiation of statin therapy in an
additional 15.8% (95% CI, 14.0%-17.5%) of patients, compared with an additional
24.3% (95% CI, 22.3%-26.3%) of patients who would be recommended for statin
initiation under full implementation of the 2013 ACC/AHA guidelines. Among the
8.9% of individuals in the primary prevention population who would be recommended
for statins by ACC/AHA guidelines but not by USPSTF recommendations, 55% would be
adults aged 40 to 59 years with a mean 30-year cardiovascular risk greater than
30%, and 28% would have diabetes. Conclusions And Relevance: In this sample of US
adults from 2009-2014, adherence to the 2016 USPSTF recommendations for statin
therapy, compared with the 2013 ACC/AHA guidelines, could lead to a lower number
of individuals recommended for primary prevention statin therapy, including many
younger adults with high mean long-term CVD risk.
PMID- 28418483
TI - Tics and Tourette Syndrome.
PMID- 28418485
TI - The Living Donor: A Tale of Money, Mania, and Clinical Mastery.
PMID- 28418482
TI - Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute
Sore Throat in Adults: A Randomized Clinical Trial.
AB - Importance: Acute sore throat poses a significant burden on primary care and is a
source of inappropriate antibiotic prescribing. Corticosteroids could be an
alternative symptomatic treatment. Objective: To assess the clinical
effectiveness of oral corticosteroids for acute sore throat in the absence of
antibiotics. Design, Setting, and Participants: Double-blind, placebo-controlled
randomized trial (April 2013-February 2015; 28-day follow-up completed April
2015) conducted in 42 family practices in South and West England, enrolled 576
adults recruited on the day of presentation to primary care with acute sore
throat not requiring immediate antibiotic therapy. Interventions: Single oral
dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283). Main
Outcomes and Measures: Primary: proportion of participants experiencing complete
resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours,
duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as
bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to
100, worst imaginable), health care attendance, days missed from work or
education, consumption of delayed antibiotics or other medications, adverse
events. Results: Among 565 eligible participants who were randomized (median age,
34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the
intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65
participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo
group achieved complete resolution of symptoms, for a risk difference of 4.7%
(95% CI, -1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P =
.14). At 24 hours, participants receiving dexamethasone were not more likely than
those receiving placebo to have complete symptom resolution. At 48 hours, 102
participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo
group achieved complete resolution of symptoms, for a risk difference of 8.7%
(95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P =
.03). This difference also was observed in participants not offered delayed
antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%)
and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no
significant differences in any other secondary outcomes. Conclusions and
Relevance: Among adults presenting to primary care with acute sore throat, a
single dose of oral dexamethasone compared with placebo did not increase the
proportion of patients with resolution of symptoms at 24 hours. However, there
was a significant difference at 48 hours. Trial Registration: isrctn.org
Identifier: ISRCTN17435450.
PMID- 28418486
TI - Is It Time to Retire?
PMID- 28418489
TI - Potential Cause of Nodding Syndrome Identified.
PMID- 28418490
TI - Depression Is the Leading Cause of Disability Around the World.
PMID- 28418487
TI - Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination
of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A
Randomized Clinical Trial. JAMA. 2014;312(14):1429-1437.
PMID- 28418491
TI - Educating Religious Leaders Increases Male Circumcision Rates in Tanzania.
PMID- 28418493
TI - The Threat of Diagnostic Uncertainty in the Medical Management of Uncomplicated
Appendicitis.
PMID- 28418492
TI - Randomized Controlled Trial in Clinical Settings to Evaluate Effectiveness of
Coping Skills Education Used With Progressive Tinnitus Management.
AB - Purpose: This randomized controlled trial evaluated, within clinical settings,
the effectiveness of coping skills education that is provided with progressive
tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300
veterans were randomized to either PTM intervention or 6-month wait-list control.
The PTM intervention involved 5 group workshops: 2 led by an audiologist
(teaching how to use sound as therapy) and 3 by a psychologist (teaching coping
skills derived from cognitive behavioral therapy). It was hypothesized that PTM
would be more effective than wait-list control in reducing functional effects of
tinnitus and that there would be no differences in effectiveness between sites.
Results: At both sites, a statistically significant improvement in mean Tinnitus
Functional Index scores was seen at 6 months for the PTM group. Combined data
across sites revealed a statistically significant improvement in Tinnitus
Functional Index relative to wait-list control. The effect size for PTM using the
Tinnitus Functional Index was 0.36 (small). Conclusions: Results suggest that PTM
is effective at reducing tinnitus-related functional distress in clinical
settings. Although effect sizes were small, they provide evidence of clinical
effectiveness of PTM in the absence of stringent research-related inclusion
criteria and with a relatively small number of sessions of cognitive behavioral
therapy.
PMID- 28418494
TI - Prevalence, Natural Course, and Prognostic Role of Refractile Drusen in Age
Related Macular Degeneration.
AB - Purpose: To report prevalence, clinical characteristics, and prognostic
significance of refractile drusen in eyes with intermediate age-related macular
degeneration (AMD). Methods: Presence of refractile drusen by color fundus
photography (CFP), corresponding findings by multimodal imaging, and longitudinal
changes with annual examinations for up to 4 years were analyzed within a
prospective natural history study of 98 eyes with non-late AMD of 98 patients
(Age-Related Eye Disease Study [AREDS] stages 3 and 4). Results: A total of 115
refractile drusen were detected at baseline in 20 eyes (20.4%). Refractile drusen
typically showed hyperreflectivity by infrared (80.9%) and blue (93.9%)
reflectance imaging, appearing more distinct when compared to CFP. Laminar
intense hyperreflectivity of Bruch's membrane was detected in 31 lesions by
spectral-domain optical coherence tomography and was strongly related to atrophy
development (23 out of 31 lesions). Presence of refractile drusen at baseline was
overall associated with later development of geographic atrophy (GA) (9/20 eyes
versus 6/78 eyes, P < 0.001). Spontaneous regression without evident atrophy
occurred in seven lesions. Conclusions: Refractile drusen are a relative common
phenotype in intermediate AMD and appear to confer risk for the development of
late AMD. While not all lesions develop late AMD and regression may also occur,
distinct subphenotypes as identified by multimodal imaging may not only be
visible earlier but also be topographically associated with the risk for GA
development. Recognizing the characteristic pattern on multimodal imaging would
inform physicians for identification of the lesion and its clinical history.
PMID- 28418495
TI - Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive
Congenital Cataracts by Homozygosity Screening.
AB - Purpose: To identify the genetic origins of autosomal recessive congenital
cataracts (arCC) in the Pakistani population. Methods: Based on the hypothesis
that most arCC patients in consanguineous families in the Punjab areas of
Pakistan should be homozygous for causative mutations, affected individuals were
screened for homozygosity of nearby highly informative microsatellite markers and
then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped
consanguineous families were screened for mutations in 33 known candidate genes.
Results: Patients in 32 arCC families were homozygous for markers near at least 1
of the 33 known CC genes. Sequencing the included genes revealed homozygous
cosegregating sequence changes in 10 families, 2 of which had the same variation.
These included five missense, one nonsense, two frame shift, and one splice site
mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1,
and CRYBA4. Conclusions: The above results confirm the usefulness of homozygosity
mapping for identifying genetic defects underlying autosomal recessive disorders
in consanguineous families. In our ongoing study of arCC in Pakistan, including
83 arCC families that underwent homozygosity mapping, 3 mapped using genome-wide
linkage analysis in unpublished data, and 30 previously reported families,
mutations were detected in approximately 37.1% (43/116) of all families studied,
suggesting that additional genes might be responsible in the remaining families.
The most commonly mutated gene was FYCO1 (14%), followed by CRYBB3 (5.2%), GALK1
(3.5%), and EPHA2 (2.6%). This provides the first comprehensive description of
the genetic architecture of arCC in the Pakistani population.
PMID- 28418497
TI - Course of Sodium Iodate-Induced Retinal Degeneration in Albino and Pigmented
Mice.
AB - Purpose: To characterize the course of sodium iodate (SI)-induced retinal
degeneration in young adult albino and pigmented mice. Methods: Single
intraperitoneal (IP) injections of SI (25, 50, and 100 mg/kg) were performed in 7
to 8-week-old BALB/c and C57Bl/6J mice. Retinal function and structure was
assessed at baseline, 24 hours, 3 days, 1, 2, 3, and 4 weeks postinjection by
optokinetic tracking response, ERG, optical coherence tomography (OCT), and
histologic and immunohistochemical techniques. Results: The 50 mg/kg SI dosage
was selected after dose ranging due to consistent retinal effects and lack of
systemic toxicity. Time-dependent deterioration in retinal function and
morphology was consistently observed between 1 and 4 weeks in all measured
parameters. These include reduction of ERG responses, thinning of retinal layers
as observed by OCT and histology, and loss of RPE nuclei. Immunohistochemistry
revealed rapid RPE disorganization with loss of tight junctions and markedly
reduced expression of RPE65 and rod opsin, accompanied by mislocalization of cone
opsins. Earlier time points displayed variable results, including partial
recovery of visual acuity at 1 week and supranormal ERG cone responses at 24
hours, suggesting possible limitations of early intervention and assessment in
the SI model. Conclusions: A single IP injection of 50 mg/kg SI leads to severe
RPE injury followed by vision impairment, dysfunction, and loss of photoreceptors
in both BALB/c and C57Bl/6J mice. This easily induced and reproducible
noninherited model may serve as a useful tool for seeking and evaluating novel
therapeutic modalities for the treatment of retinal degenerations caused by
primary failure of the RPE.
PMID- 28418498
TI - Suppression by an RAR-gamma Agonist of Collagen Degradation Mediated by Corneal
Fibroblasts.
AB - Purpose: To examine the role of retinoic acid receptor (RAR) isoforms in
interleukin-1beta (IL-1beta)-induced collagen degradation by corneal fibroblasts.
Methods: Primary rabbit corneal fibroblasts embedded in a three-dimensional
collagen gel were incubated with or without all-trans retinoic acid (ATRA), the
RAR-alpha agonist Am580, the RAR-beta agonist AC55649, or the RAR-gamma agonist
R667. Collagen degradation was determined by measurement of hydroxyproline
produced in acid hydrolysates of culture supernatants. Matrix metalloproteinase
(MMP) expression was evaluated by immunoblot analysis and gelatin zymography. The
phosphorylation of mitogen-activated protein kinases (MAPKs) and the endogenous
nuclear factor (NF)-kappaB inhibitor IkappaB-alpha was examined by immunoblot
analysis. Cell proliferation was measured with a bromodeoxyuridine incorporation
assay, and cell viability was determined by measurement of the release of lactate
dehydrogenase. Results: Interleukin-1beta-induced collagen degradation by corneal
fibroblasts was inhibited by ATRA, Am580, and R667 in a concentration-dependent
manner but was unaffected by AC55649, with the inhibitory effects of ATRA and
R667 being markedly greater than that of Am580. The IL-1beta-induced production
of MMP-1, MMP-2, MMP-3, and MMP-9 by corneal fibroblasts was also inhibited by
R667 in a concentration-dependent manner. R667 inhibited the IL-1beta-induced
phosphorylation of IkappaB-alpha but not that of MAPKs. R667 had no effect on the
proliferation or viability of corneal fibroblasts. Conclusions: The RAR-gamma
agonist R667 suppressed MMP production and thereby inhibited collagen degradation
by corneal fibroblasts exposed to the proinflammatory cytokine IL-1beta. These
effects of R667 may be mediated by the NF-kappaB signaling pathway.
PMID- 28418496
TI - Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal
Dystrophies in 144 Consanguineous Pakistani Families.
AB - Purpose: The Pakistan Punjab population has been a rich source for identifying
genes causing or contributing to autosomal recessive retinal degenerations
(arRD). This study was carried out to delineate the genetic architecture of arRD
in the Pakistani population. Methods: The genetic origin of arRD in a total of
144 families selected only for having consanguineous marriages and multiple
members affected with arRD was examined. Of these, causative mutations had been
identified in 62 families while only the locus had been identified for an
additional 15. The remaining 67 families were subjected to homozygosity exclusion
mapping by screening of closely flanking microsatellite markers at 180 known
candidate genes/loci followed by sequencing of the candidate gene for pathogenic
changes. Results: Of these 67 families subjected to homozygosity mapping, 38
showed homozygosity for at least one of the 180 regions, and sequencing of the
corresponding genes showed homozygous cosegregating mutations in 27 families.
Overall, mutations were detected in approximately 61.8 % (89/144) of arRD
families tested, with another 10.4% (15/144) being mapped to a locus but without
a gene identified. Conclusions: These results suggest the involvement of unmapped
novel genes in the remaining 27.8% (40/144) of families. In addition, this study
demonstrates that homozygosity mapping remains a powerful tool for identifying
the genetic defect underlying genetically heterogeneous arRD disorders in
consanguineous marriages for both research and clinical applications.
PMID- 28418499
TI - Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts
After Filtration Surgery for Glaucoma.
AB - Purpose: To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid
samples taken before and after filtration surgery and S1P-induced human
conjunctival fibroblast (HCF) responses. Methods: Levels of S1P and its related
sphingophospholipids in aqueous fluid obtained immediately before and after
filtration surgery were determined by liquid chromatography-tandem mass
spectrometry. HCFs were used for all in vitro experiments. The expression of five
S1P receptor subtypes in HCFs was examined by quantitative real-time PCR. The
effect of S1P and receptor-specific antagonists on HCF viability and cell
migration was assessed by WST-1 assay and scratch migration assay, respectively.
Differentiation to myofibroblasts and extracellular matrix production was
evaluated by examining changes in F-actin, alpha-smooth muscle actin (alphaSMA),
and collagen expression with immunocytochemistry, Western blotting, and collagen
accumulation assay, respectively. Results: No significant S1P levels in the
aqueous fluid samples were detectable immediately before surgery, but
postoperative levels of several lysophospholipids, including S1P, dehydro-S1P,
and sphingosine, were significantly increased to bioactive concentrations in
aqueous fluid in the blebs (P < 0.0001). mRNA expression of the three main S1P
receptor subtypes was detected in HCFs. Although S1P levels did not influence HCF
proliferation, S1P enhanced cell migration, which could be inhibited by the S1P2
antagonist JTE 013. F-actin, alphaSMA, and collagen expression was significantly
increased by S1P stimulation and was reduced by JTE 013. Conclusions: Bioactive
S1P concentrations were present in the aqueous fluid at the end of filtration
surgery. S1P activated HCFs via S1P2 receptors. These results revealed the
potential of S1P2 antagonists in preventing scarring after glaucoma filtration
surgery.
PMID- 28418501
TI - Cost Effectiveness of Wait Time Reduction in Behavioral Interventions for Autism
Reply.
PMID- 28418502
TI - Tumor Sidedness and Prognosis in Colorectal Cancer: Is Microbiome the Missing
Link?
PMID- 28418500
TI - Risk of Uveitis Among People With Psoriasis: A Nationwide Cohort Study.
AB - Importance: Uveitis has been associated with psoriatic arthritis, but to our
knowledge, the relationship between uveitis and psoriasis is unsettled among
researchers. Objective: To evaluate the risk of incident uveitis among people
with psoriasis. Design, Setting, and Participants: This nationwide, retrospective
cohort study conducted in Taiwan from January 1, 2000, to December 31, 2012
included 147 954 people with psoriasis (including 10 107 with concomitant
psoriatic arthritis and 137 847 without psoriatic arthritis) and 147 954
nonpsoriatic controls. Exposure: Psoriasis. Main Outcomes and Measures: Risk of
incident uveitis. Results: The mean (SD) age of the 295 908 study participants
was 44.4 (19.8) years, and 41.2% (n = 121 878) were women. We found that the
group with severe psoriasis with psoriatic arthritis had the greatest risk of
incident uveitis compared with the nonpsoriatic controls (adjusted hazard ratio,
2.40; 95% CI, 1.90-3.02). The group with severe psoriasis without psoriatic
arthritis and the group with mild psoriasis with psoriatic arthritis also had an
increased risk of incident uveitis (adjusted hazard ratio, 1.42; 95% CI, 1.23
1.64; and 1.42; 95% CI, 1.03-1.96; respectively). However, an increased risk for
incident uveitis with mild psoriasis without psoriatic arthritis was not
identified (adjusted hazard ratio, 1.09; 95% CI, 1.00-1.20). Conclusions and
Relevance: People with severe psoriasis and those with mild psoriasis have an
increased risk of uveitis. Clinicians may use this finding as a guide for uveitis
risk stratification among patients with different inflammatory presentations on
the spectrum of psoriatic disease.
PMID- 28418503
TI - Enhanced Epilepsy Surveillance and Awareness in the Age of Zika.
PMID- 28418504
TI - Alternative Facts Have No Place in Science.
PMID- 28418505
TI - Acute and Painless Monocular Vision Loss in a Human Immunodeficiency Virus
Positive Man.
PMID- 28418506
TI - Divergence Compensatory Optical Flow Method for Blood Velocimetry.
AB - Detailed blood velocity map in the vascular system can be obtained by applying
the optical flow method (OFM) in processing fluoroscopic digital subtracted
catheter angiographic images; however, there are still challenges with the
accuracy of this method. In the present study, a divergence compensatory optical
flow method (DC-OFM), in which a nonzero divergence of velocity is assumed due to
the finite resolution of the image, was explored and applied to the digital
subtraction angiography (DSA) images of blood flow. The objective of this study
is to examine the applicability and evaluate the accuracy of DC-OFM in assessing
the blood flow velocity in vessels. First, an Oseen vortex flow was simulated on
the standard particle image to generate an image pair. Then, the DC-OFM was
applied on the particle image pair to recover the velocity field for validation.
Second, DSA images of intracranial arteries were used to examine the accuracy of
the current method. For each set of images, the first image is the in vivo DSA
image, and the second image is generated by superimposing a given flow field. The
recovered velocity map by DC-OFM agrees well with the exact velocity for both the
particle images and the angiographic images. In comparison with the traditional
OFM, the present method can provide more accurate velocity estimation. The
accuracy of the velocity estimation can also be improved by implementing
preprocess techniques including image intensification, Gaussian filtering, and
"image-shift."
PMID- 28418507
TI - Use of Bayesian Decision Analysis to Minimize Harm in Patient-Centered Randomized
Clinical Trials in Oncology.
AB - Importance: Randomized clinical trials (RCTs) currently apply the same
statistical threshold of alpha = 2.5% for controlling for false-positive results
or type 1 error, regardless of the burden of disease or patient preferences. Is
there an objective and systematic framework for designing RCTs that incorporates
these considerations on a case-by-case basis? Objective: To apply Bayesian
decision analysis (BDA) to cancer therapeutics to choose an alpha and sample size
that minimize the potential harm to current and future patients under both null
and alternative hypotheses. Data Sources: We used the National Cancer Institute
(NCI) Surveillance, Epidemiology, and End Results (SEER) database and data from
the 10 clinical trials of the Alliance for Clinical Trials in Oncology. Study
Selection: The NCI SEER database was used because it is the most comprehensive
cancer database in the United States. The Alliance trial data was used owing to
the quality and breadth of data, and because of the expertise in these trials of
one of us (D.J.S.). Data Extraction and Synthesis: The NCI SEER and Alliance data
have already been thoroughly vetted. Computations were replicated independently
by 2 coauthors and reviewed by all coauthors. Main Outcomes and Measures: Our
prior hypothesis was that an alpha of 2.5% would not minimize the overall
expected harm to current and future patients for the most deadly cancers, and
that a less conservative alpha may be necessary. Our primary study outcomes
involve measuring the potential harm to patients under both null and alternative
hypotheses using NCI and Alliance data, and then computing BDA-optimal type 1
error rates and sample sizes for oncology RCTs. Results: We computed BDA-optimal
parameters for the 23 most common cancer sites using NCI data, and for the 10
Alliance clinical trials. For RCTs involving therapies for cancers with short
survival times, no existing treatments, and low prevalence, the BDA-optimal type
1 error rates were much higher than the traditional 2.5%. For cancers with longer
survival times, existing treatments, and high prevalence, the corresponding BDA
optimal error rates were much lower, in some cases even lower than 2.5%.
Conclusions and Relevance: Bayesian decision analysis is a systematic, objective,
transparent, and repeatable process for deciding the outcomes of RCTs that
explicitly incorporates burden of disease and patient preferences.
PMID- 28418508
TI - Lower Cervical Spine Motion Segment Computational Model Validation: Kinematic and
Kinetic Response for Quasi-Static and Dynamic Loading.
AB - Advanced computational human body models (HBM) enabling enhanced safety require
verification and validation at different levels or scales. Specifically, the
motion segments, which are the building blocks of a detailed neck model, must be
validated with representative experimental data to have confidence in segment
and, ultimately, full neck model response. In this study, we introduce detailed
finite element motion segment models and assess the models for quasi-static and
dynamic loading scenarios. Finite element segment models at all levels in the
lower human cervical spine were developed from scans of a 26-yr old male subject.
Material properties were derived from the in vitro experimental data. The segment
models were simulated in quasi-static loading in flexion, extension, lateral
bending and axial rotation, and at dynamic rates in flexion and extension in
comparison to previous experimental studies and new dynamic experimental data
introduced in this study. Single-valued experimental data did not provide
adequate information to assess the model biofidelity, while application of
traditional corridor methods highlighted that data sets with higher variability
could lead to an incorrect conclusion of improved model biofidelity. Data sets
with continuous or multiple moment-rotation measurements enabled the use of cross
correlation for an objective assessment of the model and highlighted the
importance of assessing all motion segments of the lower cervical spine to
evaluate the model biofidelity. The presented new segment models of the lower
cervical spine, assessed for range of motion and dynamic/traumatic loading
scenarios, provide a foundation to construct a biofidelic model of the spine and
neck, which can be used to understand and mitigate injury for improved human
safety in the future.
PMID- 28418510
TI - Finding Youths at Risk for HIV Infection: Targeted Testing, Universal Testing, or
Both?
PMID- 28418509
TI - Association of Preoperative Calcium and Calcitriol Therapy With Postoperative
Hypocalcemia After Total Thyroidectomy.
AB - Importance: Hypocalcemia is the most common complication after total
thyroidectomy and can result in prolonged hospital admissions and increased
hospital charges. Objective: To determine the effectiveness of preoperative
calcium and calcitriol supplementation in reducing hypocalcemia following total
thyroidectomy. Design, Setting, and Participants: A retrospective cohort study
was conducted at a tertiary care center in 65 patients undergoing total
thyroidectomy by a single surgeon. Patients were divided into 2 groups: those
receiving preoperative as well as postoperative supplementation with calcium
carbonate, 1000 to 1500 mg, 3 times daily and calcitriol, 0.25 to 0.5 ug, twice
daily, and those receiving only postoperative supplementation with those agents
at the same dosages. Data on patients who underwent surgery between January 1,
2008, and December 31, 2011, were acquired, and data analyses were conducted from
March through June 2012, and from October through December 2016. Interventions:
Calcium and calcitriol therapy. Main Outcomes and Measures: Postoperative serum
calcium levels and development of postoperative hypocalcemia. Results: Of the 65
patients who underwent total thyroidectomy 27 (42%) were men; mean (SD) age was
49.7 (16.7) years. Thirty-three patients received preoperative calcium and
calcitriol supplementation, and 32 patients received only postoperative therapy.
In the preoperative supplementation group, 15 of 33 (45%) patients underwent
complete central compartment neck dissection and 11 of 33 (33%) had lateral neck
dissection, compared with 16 of 32 (50%) and 12 of 32 (38%), respectively,
patients without preoperative supplementation. The mean measured serum calcium
level in those without preoperative supplementation vs those with supplementation
are as follows: preoperative, 9.6 vs 9.4 mg/dL (absolute difference, 0.16; 95%
CI, -0.12 to 0.49 mg/dL); 12 hours postoperative, 8.3 vs 8.6 mg/dL (absolute
difference, -0.30; 95% CI, -0.63 to 0.02 mg/dL); and 24 hours postoperative, 8.4
vs 8.5 mg/dL (absolute difference, -0.13; 95% CI, -0.43 to 0.16 mg/dL). In
patients not receiving preoperative supplementation, 5 of 32 (16%) individuals
became symptomatically hypocalcemic vs 2 of 33 (6%) in the preoperative
supplementation group; an absolute difference of 10% (95% CI, -6.6% to 26.3%).
Compared with the group not receiving preoperative supplementation, the mean [SD]
length of stay was significantly shorter in the preoperative supplementation
group (3.8 [1.8] vs 2.9 [1.4] days; absolute difference, -0.9; 95% CI, -1.70 to
0.105 days). Preoperative supplementation resulted in an estimated $2819 savings
in charges per patient undergoing total thyroidectomy. Conclusions and Relevance:
Preoperative calcium and calcitriol supplementation, in addition to routine
postoperative supplementation, was associated with a reduced incidence of
symptomatic hypocalcemia, length of hospital stay, and overall charges following
total thyroidectomy.
PMID- 28418511
TI - Early Palliative Care in Advanced Illness: Do Right by Mama.
PMID- 28418512
TI - A Method for In Vitro TCPC Compliance Verification.
AB - The Fontan procedure is a common palliative intervention for sufferers of single
ventricle congenital heart defects that results in an anastomosis of the venous
return to the pulmonary arteries called the total cavopulmonary connection
(TCPC). Local TCPC and global Fontan circulation hemodynamics are studied with in
vitro circulatory models because of hemodynamic ties to Fontan patient long-term
complications. The majority of in vitro studies, to date, employ a rigid TCPC
model. Recently, a few studies have incorporated flexible TCPC models, but
provide no justification for the model material properties. The method set forth
in this study successfully utilizes patient-specific flow and pressure data from
phase contrast magnetic resonance images (PCMRI) (n = 1) and retrospective pulse
pressure data from an age-matched patient cohort (n = 10) to verify the
compliance of an in vitro TCPC model. These data were analyzed, and the target
compliance was determined as 1.36 +/- 0.78 mL/mm Hg. A method of in vitro
compliance testing and computational simulations was employed to determine the in
vitro flexible TCPC model material properties and then use those material
properties to estimate the wall thickness necessary to match the patient-specific
target compliance. The resulting in vitro TCPC model compliance was 1.37 +/- 0.1
mL/mm Hg-a value within 1% of the patient-specific compliance. The presented
method is useful to verify in vitro model accuracy of patient-specific TCPC
compliance and thus improve patient-specific hemodynamic modeling.
PMID- 28418516
TI - Cost-effectiveness of Wait Time Reduction in Behavioral Interventions for Autism.
PMID- 28418515
TI - Pronation-Supination Motion Is Altered in a Rat Model of Post-Traumatic Elbow
Contracture.
AB - The elbow joint is highly susceptible to joint contracture, and treating elbow
contracture is a challenging clinical problem. Previously, we established an
animal model to study elbow contracture that exhibited features similar to the
human condition including persistent decreased range of motion (ROM) in flexion
extension and increased capsule thickness/adhesions. The objective of this study
was to mechanically quantify pronation-supination in different injury models to
determine if significant differences compared to control or contralateral persist
long-term in our animal elbow contracture model. After surgically inducing soft
tissue damage in the elbow, Injury I (anterior capsulotomy) and Injury II
(anterior capsulotomy with lateral collateral ligament transection), limbs were
immobilized for 6 weeks (immobilization (IM)). Animals were evaluated after the
IM period or following an additional 6 weeks of free mobilization (FM). Total ROM
for pronation-supination was significantly decreased compared to the uninjured
contralateral limb for both IM and FM, although not different from control limbs.
Specifically, for both IM and FM, total ROM for Injury I and Injury II was
significantly decreased by ~20% compared to contralateral. Correlations of
measurements from flexion-extension and pronation-supination divulged that FM did
not affect these motions in the same way, demonstrating that joint motions need
to be studied/treated separately. Overall, injured limbs exhibited persistent
motion loss in pronation-supination when comparing side-to-side differences,
similar to human post-traumatic joint contracture. Future work will use this
animal model to study how elbow periarticular soft tissues contribute to
contracture.
PMID- 28418517
TI - March for Science.
PMID- 28418518
TI - Development of a Research Agenda to Identify Evidence-Based Strategies to Improve
Physician Wellness and Reduce Burnout.
PMID- 28418519
TI - Association of Diet With Skin Histological Features in UV-B-Exposed Mice.
AB - Importance: Long-term exposure to solar radiation produces deleterious photoaging
of the skin. It is not known if diet can influence skin photoaging. Objectives:
To study the influence of a calorie-restricted diet and an obesity diet in mice
exposed to long-term UV-B irradiation to assess if there is an association
between diet and histopathological response to UV-B irradiation. Design, Setting,
and Participants: In this animal model study in an academic setting, the dorsal
skin of SKH1 hairless mice receiving normal, calorie-restricted, and obesity
diets was exposed to UV-B irradiation 3 times a week for 10 weeks and were
compared with corresponding controls. The mice were placed in the following
groups, with 8 animals in each group: (1) intact control (C) with regular diet
and no UV-B exposure, (2) intact control with UV-B exposure (CR), (3) calorie
restricted diet (CrC), (4) calorie-restricted diet with UV-B exposure (CrR), (5)
obesity diet (OC), and (6) obesity diet with UV-B exposure (OR). The experiment
was conducted during October through December 2013. Tissue processing and
histological analysis were completed in 2016. Main Outcomes and Measures:
Histomorphometric analysis was performed on paraffin-embedded skin sections
stained by histological and immunohistochemical methods for estimation of
epidermal thickness, epidermal proliferating cell nuclear antigen index, collagen
I, elastic fibers, fibroblasts, mast cells, dermal cellularity, and adipose layer
ratio. Changes in wrinkles were noted. Results: Hairless female mice (age range,
6-8 weeks) were obtained. With a normal diet, changes from UV-B irradiation
occurred in epidermal thickness, epidermal proliferating cell nuclear antigen
index, collagen I, elastic fibers, fibroblasts, and mast cells, which were
modestly influenced by an obesity diet. Calorie restriction influenced the skin
in nonirradiated control animals, with higher values for most variables. After UV
B exposure in animals with calorie restriction, epidermal thickness was
increased, but other variables were unaffected. Animals receiving the calorie
restricted diet lost weight when exposed to long-term UV-B irradiation. Wrinkles
were reduced in the calorie-restricted control group and in UV-B-exposed animals
who received the obesity diet. Conclusions and Relevance: Dietary alterations
seem to modify histopathological responses to UV-B exposure in the skin of
hairless mice. Level of Evidence: NA.
PMID- 28418520
TI - Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity
Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta
analysis.
AB - Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are
sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To
estimate the ability of a single hs-cTnT concentration below the limit of
detection (<0.005 ug/L) and a nonischemic electrocardiogram (ECG) to rule out AMI
in adults presenting to the emergency department (ED) with chest pain. Data
Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14
December 2016). Study Selection: Cohort studies involving adults presenting to
the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT
measurements were obtained and AMI outcomes adjudicated during initial
hospitalization. Data Extraction: Investigators of studies provided data on the
number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements
<0.005 ug/L) and the number who had AMI during hospitalization (primary outcome)
or a major adverse cardiac event (MACE) or death within 30 days (secondary
outcomes), by risk classification (low or not low risk). Two independent
epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients
in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%)
low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged
from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7%
(95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%;
pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died.
Limitation: Few studies, variation in timing and methods of reference standard
troponin tests, and heterogeneity of risk and prevalence of AMI across studies.
Conclusion: A single hs-cTnT concentration below the limit of detection in
combination with a nonischemic ECG may successfully rule out AMI in patients
presenting to EDs with possible emergency acute coronary syndrome. Primary
Funding Source: Emergency Care Foundation.
PMID- 28418522
TI - A Young Man With Proptosis Causing Decreased Visual Acuity.
PMID- 28418521
TI - Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration
Protective Factors in Elderly Individuals.
AB - Importance: While amyloid and neurodegeneration are viewed together as Alzheimer
disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern
neurodegeneration may be considerably different. Protection from these ADP
factors may be important for aging without significant ADP. Objective: To
identify the combined and independent protective factors for amyloid and AD
pattern neurodegeneration in a population-based sample and to test the hypothesis
that "exceptional agers" with advanced ages do not have significant ADP because
they have protective factors for amyloid and neurodegeneration. Design, Setting,
and Participants: This cohort study conducted a prospective analysis of 942
elderly individuals (70->=90 years) with magnetic resonance imaging and
Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo
Clinic Study of Aging, a longitudinal population-based study of cognitive aging
in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP
by considering individuals 85 years or older to be without significant evidence
of ADP. Main Outcomes and Measures: We evaluated predictors including
demographics, APOE, intellectual enrichment, midlife risk factors (physical
inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the
total number of late-life cardiac and metabolic conditions. We used multivariate
linear regression models to identify the combined and independent protective
factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the
cohort 85 years of age or older, we computed Cohen d-based effect size
estimations to compare the quantitative strength of each predictor variable in
their contribution with exceptional aging without ADP. Results: The study
participants included 423 (45%) women and the average age of participants was
79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife
dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes,
hypertension, and cardiac and metabolic conditions, but not intellectual
enrichment, were associated with greater AD-pattern neurodegeneration. In the 85
years or older cohort, the Cohen d results showed small to moderate effects
(effect sizes > 0.2) of several variables except job score and midlife
hypertension in predicting exceptional aging without ADP. Conclusions and
Relevance: The protective factors that influence amyloid and AD-pattern
neurodegeneration are different. "Exceptional aging" without ADP may be possible
with a greater number of protective factors across the lifespan but warrants
further investigation.
PMID- 28418523
TI - Neurocognitive Trajectory of Boys Who Received a Hematopoietic Stem Cell
Transplant at an Early Stage of Childhood Cerebral Adrenoleukodystrophy.
AB - Importance: Untreated childhood cerebral adrenoleukodystrophy (cALD) is a fatal
disease associated with progressive cerebral demyelination and rapid, devastating
neurologic decline. The standard of care to enhance long-term survival and
stabilize cerebral disease is a hematopoietic stem cell transplant (HSCT).
Neurologic outcomes are better when HSCT occurs at an earlier stage of cALD, yet
there is limited understanding of the neurocognitive trajectory of patients who
undergo HSCT. Objectives: To characterize neurocognitive outcomes of boys with
cALD and early-stage cerebral disease who were treated with an allogeneic HSCT
and to identify disease- and treatment-related factors associated with long-term
functioning. Design, Setting, and Participants: Baseline and follow-up
neurocognitive test performance was analyzed for all boys with cALD who received
an HSCT at the University of Minnesota between January 1, 1991, and October 20,
2014, and who had a pretransplant magnetic resonance imaging (MRI) severity score
of less than 10 (scale range, 0-34; higher scores indicate greater severity).
Main Outcomes and Measures: Longitudinal neurocognitive test performance in 4
domains (verbal comprehension, perceptual [visual] reasoning, working memory, and
processing speed) were the primary outcome measures. Secondary analysis at the
most recent evaluation also included measures of sustained attention, verbal
memory, visual-motor integration, and fine motor function. Results: Among the 62
boys in this study (mean [SD] age at transplant, 8.37 [2.80] years; range, 4-16
years), there was a significant association of pretransplant MRI severity and
baseline verbal comprehension (r = -0.340; P = .008), perceptual reasoning (r =
0.419; P = .001), and processing speed (r = -0.285; P = .03) scores. Higher
pretransplant MRI severity scores were also associated with a steeper decline in
neurocognitive functioning during the 5-year follow-up period. Twenty-two of 33
patients (67%) with available long-term follow-up neurocognitive testing had
severe impairment in at least 1 neurocognitive domain at the most recent
evaluation. Conclusions and Relevance: Boys with cALD who have greater than
minimal cerebral disease detected on MRI scans at the time of an HSCT are at risk
for severe, persistent neurocognitive deficits. These findings motivate further
exploration of methods of detecting cerebral disease prior to development of
lesions observable on MRI scans, an endeavor that may be facilitated by newborn
screening for adrenoleukodystrophy. These findings may serve a benchmark role in
evaluating the efficacy of novel interventions for cALD.
PMID- 28418525
TI - Asymptomatic Microscopic Hematuria-Rethinking the Diagnostic Algorithm.
PMID- 28418524
TI - Evaluating Testing Strategies for Identifying Youths With HIV Infection and
Linking Youths to Biomedical and Other Prevention Services.
AB - Importance: Most human immunodeficiency virus (HIV)-infected youths are unaware
of their serostatus (approximately 60%) and therefore not linked to HIV medical
or prevention services. The need to identify promising and scalable approaches to
promote uptake of HIV testing among youths at risk is critical. Objective: To
evaluate a multisite HIV testing program designed to encourage localized HIV
testing programs focused on self-identified sexual minority males and to link
youths to appropriate prevention services after receipt of their test results.
Design, Setting, and Participants: Testing strategies were evaluated using an
observational design during a 9-month period (June 1, 2015, through February 28,
2016). Testing strategies were implemented by 12 adolescent medicine HIV primary
care programs and included targeted testing, universal testing, or a combination.
Data were collected from local youth at high risk of HIV infection and,
specifically, sexual minority males of color. Main Outcomes and Measures:
Proportion of sexual minority males and sexual minority males of color tested,
proportion of previously undiagnosed HIV-positive youths identified, and rates of
linkage to prevention services. Results: A total of 3301 youths underwent HIV
testing. Overall, 35 (3.6%) of those who underwent universal testing in primary
care clinical settings, such as emergency departments and community health
centers, were sexual minority males (35 [3.6%] were males of color) compared with
236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted
testing and 693 (37.8%) (503 [27.4%] were males of color) through combination
efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%)
via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%)
through targeted testing. However, when targeted tests were separated from
universal testing results for sites using a combined strategy, the rate of newly
identified HIV-positive cases identified through universal testing decreased to 1
(0.1%). Rates of new HIV-positive cases identified through targeted testing
increased to 49 (6.3%). Youths who tested through targeted testing (416 [85.1%])
were more likely to link successfully to local HIV prevention services, including
preexposure prophylaxis, compared with those who underwent universal testing (328
[34.1%]). Conclusions and Relevance: The findings suggest that community-based
targeted approaches to HIV testing are more effective than universal screening
for reaching young sexual minority males (especially males of color), identifying
previously undiagnosed HIV-positive youths, and linking HIV-negative youths to
relevant prevention services. Targeted, community-based HIV testing strategies
hold promise as a scalable and effective means to identify high-risk youths who
are unaware of their HIV status.
PMID- 28418526
TI - Empirically Determined Vascular Smooth Muscle Cell Mechano-Adaptation Law.
AB - Cardiovascular disease can alter the mechanical environment of the vascular
system, leading to mechano-adaptive growth and remodeling. Predictive models of
arterial mechano-adaptation could improve patient treatments and outcomes in
cardiovascular disease. Vessel-scale mechano-adaptation includes remodeling of
both the cells and extracellular matrix. Here, we aimed to experimentally measure
and characterize a phenomenological mechano-adaptation law for vascular smooth
muscle cells (VSMCs) within an artery. To do this, we developed a highly
controlled and reproducible system for applying a chronic step-change in strain
to individual VSMCs with in vivo like architecture and tracked the temporal
cellular stress evolution. We found that a simple linear growth law was able to
capture the dynamic stress evolution of VSMCs in response to this mechanical
perturbation. These results provide an initial framework for development of
clinically relevant models of vascular remodeling that include VSMC adaptation.
PMID- 28418527
TI - Initial Public Reporting of Quality at Veterans Affairs vs Non-Veterans Affairs
Hospitals.
PMID- 28418528
TI - Understanding Veteran Wait Times.
PMID- 28418529
TI - Anxiety in 11-Year-Old Children Who Stutter: Findings From a Prospective
Longitudinal Community Sample.
AB - Purpose: To examine if a community sample of 11-year-old children with persistent
stuttering have higher anxiety than children who have recovered from stuttering
and nonstuttering controls. Method: Participants in a community cohort study were
categorized into 3 groups: (a) those with persistent stuttering, (b) those with
recovered stuttering, and (c) nonstuttering controls. Linear regression modeling
compared outcomes on measures of child anxiety and emotional and behavioral
functioning for the 3 groups. Results: Without adjustment for covariates
(unadjusted analyses), the group with persistent stuttering showed significantly
increased anxiety compared with the recovered stuttering group and nonstuttering
controls. The group with persistent stuttering had a higher number of children
with autism spectrum disorder and/or learning difficulties. Once these variables
were included as covariates in subsequent analysis, there was no difference in
anxiety, emotional and behavioral functioning, or temperament among groups.
Conclusion: Although recognized to be associated with stuttering in clinical
samples, anxiety was not higher in school-age children who stutter in a community
cohort. It may be that anxiety develops later or is less marked in community
cohorts compared with clinical samples. We did, however, observe higher anxiety
scores in those children who stuttered and had autism spectrum disorder or
learning difficulties. Implications and recommendations for research are
discussed.
PMID- 28418530
TI - Hiding in Plain Sight-Resurrecting the Power of Inspecting the Patient.
PMID- 28418531
TI - Solutions Not Problems: A New Era in After-Hours Care?
PMID- 28418532
TI - Auditory Environment Across the Life Span of Cochlear Implant Users: Insights
From Data Logging.
AB - Purpose: We describe the natural auditory environment of people with cochlear
implants (CIs), how it changes across the life span, and how it varies between
individuals. Method: We performed a retrospective cross-sectional analysis of
Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from
1,501 people with CIs (ages 0-96 years). They covered over 2.4 million hr of
implant use and indicated how much time the CI users had spent in various
acoustical environments. We investigated exposure to spoken language, noise,
music, and quiet, and analyzed variation between age groups, users, and
countries. Results: CI users spent a substantial part of their daily life in
noisy environments. As a consequence, most speech was presented in background
noise. We found significant differences between age groups for all auditory
scenes. Yet even within the same age group and country, variability between
individuals was substantial. Conclusions: Regardless of their age, people with
CIs face challenging acoustical environments in their daily life. Our results
underline the importance of supporting them with assistive listening technology.
Moreover, we found large differences between individuals' auditory diets that
might contribute to differences in rehabilitation outcomes. Their causes and
effects should be investigated further.
PMID- 28418533
TI - Association of a Chronic Stress Biomarker With Advanced Development of Breast and
Testicular Volume.
PMID- 28418535
TI - Breath analysis using external cavity diode lasers: a review.
AB - Most techniques that are used for diagnosis and therapy of diseases are invasive.
Reliable noninvasive methods are always needed for the comfort of patients. Owing
to its noninvasiveness, ease of use, and easy repeatability, exhaled breath
analysis is a very good candidate for this purpose. Breath analysis can be
performed using different techniques, such as gas chromatography mass
spectrometry (MS), proton transfer reaction-MS, and selected ion flow tube-MS.
However, these devices are bulky and require complicated procedures for sample
collection and preconcentration. Therefore, these are not practical for routine
applications in hospitals. Laser-based techniques with small size, robustness,
low cost, low response time, accuracy, precision, high sensitivity, selectivity,
low detection limit, real-time, and point-of-care detection have a great
potential for routine use in hospitals. In this review paper, the recent advances
in the fields of external cavity lasers and breath analysis for detection of
diseases are presented.
PMID- 28418536
TI - Near-infrared angiography for critical limb ischemia in a diabetic murine model.
AB - Peripheral arterial disease (PAD) is a highly prevalent disease process that
afflicts more than 20% of individuals with diabetes. Progression of PAD in the
setting of diabetes can lead to critical limb ischemia (CLI), which is associated
with increased risk of wounds, gangrene, and limb loss. Prompt noninvasive
evaluation of limbs affected by PAD progression and CLI is currently limited.
Here, we evaluate the utility of a custom-designed multispectral imaging system
for fluorescence-based near-infrared angiography and compare it to the existing
gold standard of laser-scanning Doppler perfusion assessments. Due to its higher
resolution and fluorescence sensitivity, near-infrared angiography demonstrates a
greater capacity to characterize altered dynamic arterial perfusion in a
clinically relevant diabetic murine model for CLI. Furthermore, we demonstrate
that our imaging system can accurately track arterial perfusion recovery over
time following induced ischemia, and reveal unique phenotypic differences in the
setting of diabetes.
PMID- 28418537
TI - Assessment of decellularization of heart bioimplants using a Raman spectroscopy
method.
AB - We report the results of experimental studies on cardiac implants using a Raman
spectroscopy method (RS). Raman spectra characteristics of leaves and walls of
cardiac implants were obtained; the implants were manufactured by protocols of
detergent-enzymatic technique (DET) and biological, detergent-free (BIO)
decellularization, using detergents (group DET) or a detergent-free,
nonproteolytic, actin-disassembling regimen (BIO). There were input optical
coefficients that allowed us to carry out evaluation of the protocols of DET and
BIO decellularization on the basis of the concentrations of glycosaminoglycans,
proteins, amides, and DNA. It was shown that during DET and BIO
decellularization, composition aberrations of proteins and lipids do not occur
and the integrity of the collagenous structures is preserved. It was found that
during the DET decellularization, preservation of glycosaminoglycans is better
than during BIO decellularization.
PMID- 28418534
TI - Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas:
standardization and quantitative comparison with histology.
AB - Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image
contrast in many tumors due to the increased accumulation of protoporphyrin IX
(PpIX), a fluorescent porphyrin that is associated with tumor burden and
proliferation. The value of PpIX-guided resection of malignant gliomas has been
demonstrated in prospective randomized clinical studies in which a twofold
greater extent of resection and improved progression-free survival have been
observed. In low-grade gliomas and at the diffuse infiltrative margins of all
gliomas, PpIX fluorescence is often too weak to be detected with current low
resolution surgical microscopes that are used in operating rooms. However, it has
been demonstrated that high-resolution optical-sectioning microscopes are capable
of detecting the sparse and punctate accumulations of PpIX that are undetectable
via conventional low-power surgical fluorescence microscopes. To standardize the
performance of high-resolution optical-sectioning devices for future clinical
use, we have developed an imaging phantom and methods to ensure that the imaging
of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging
studies with a dual-axis confocal microscope demonstrate that these methods
enable the acquisition of images from unsectioned human brain tissues that
quantitatively and consistently correlate with images of histologically processed
tissue sections.
PMID- 28418538
TI - Changing Mindsets to Enhance Treatment Effectiveness.
PMID- 28418539
TI - Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela.
AB - Importance: The ocular manifestations and sequelae of Zika virus infection are
not well known. Recently, the World Health Organization changed the declaration
of Zika as a public health emergency and designated the viral outbreak and
related microcephaly clusters as a long-term program of work. This change
indicates the urgent need to evaluate and document ophthalmic manifestations in
patients for timely management of this disease. In addition, confirmation whether
the public health problem in Brazil extends to other regions in South America is
needed. Objective: To report the ocular manifestations of congenital Zika
syndrome with microcephaly in Colombia and Venezuela. Design, Setting, and
Participants: This prospective case series included 43 patients from 2 ophthalmic
centers in Colombia and Venezuela who underwent evaluation from October 1, 2015,
through June 30, 2016, and were clinically diagnosed with congenital Zika
syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native
American. Interventions: Ophthalmic and systemic evaluations and serologic
testing were performed on all infants. Patients underwent external ocular
examination and dilated ophthalmoscopy. Serologic testing ruled out
toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency
virus. Main Outcomes and Measures: Ophthalmic manifestations of congenital Zika
syndrome. Results: Of the 43 patients included in this series (28 female and 15
male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all
the children had no ophthalmic findings and did not report ocular symptoms during
pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve
findings included hypoplasia with the double-ring sign, pallor, and increased cup
disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe
pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%).
Chorioretinal scarring was present in 3 patients (7%). Eleven patients (26%) had
a combination of lesions in the posterior pole. Five patients (12%) were
diagnosed with congenital glaucoma, characterized by the clinical triad of
epiphora, photophobia, and blepharospasm; increased intraocular pressure; corneal
clouding at birth; and buphthalmos. These data reveal that 12% (95% CI, 5%-24%)
of cases of congenital Zika with microcephaly had anterior segment abnormalities
and 88% (95% CI, 76%-94%) had important macular and optic nerve abnormalities.
The visual sequelae of these ophthalmic manifestations remain unknown.
Conclusions and Relevance: Congenital Zika syndrome in the current study had
severe ocular abnormalities, and all patients had bilateral involvement. Ocular
findings were focal macular pigment mottling, chorioretinal atrophy with a
predilection for the macular area, congenital glaucoma and optical nerve
hypoplasia, and optic disc abnormalities. Ophthalmic examination is recommended
in patients with congenital Zika syndrome.
PMID- 28418540
TI - Guideline: ACP and AAFP recommend systolic BP targets based on history and risk
level in adults >= 60 years of age.
PMID- 28418541
TI - Guideline: In type 2 diabetes, ACP recommends metformin monotherapy if drugs are
needed for glycemic control.
PMID- 28418542
TI - Review: Sulfonylureas are associated with overall mortality and CV events vs
other antihyperglycemics in T2DM.
PMID- 28418543
TI - Review: HbA1c has low accuracy for prediabetes; lifestyle programs and metformin
reduce progression to T2DM.
PMID- 28418544
TI - Review: In patients with ureteric lithiasis, alpha-blockers increase stone
expulsion.
PMID- 28418545
TI - Review: In CAD without HF, RAS inhibitors reduce deaths more than placebo but not
active control.
PMID- 28418546
TI - In patients in the emergency department with acute pain, 10, 15, and 30 mg of
ketorolac did not differ for pain relief.
PMID- 28418547
TI - Review: Adding anticholinergics to beta2-agonists for asthma exacerbations
reduces hospitalizations.
PMID- 28418548
TI - Review: Metformin is linked to reduced mortality in type 2 diabetes with comorbid
CKD and CHF.
PMID- 28418549
TI - Glasgow Blatchford score predicted intervention or death better than 4 other
prediction models in upper GI bleeding.
PMID- 28418550
TI - Cost-Effectiveness of Sacubitril-Valsartan in Patients Who Have Heart Failure
With Reduced Ejection Fraction.
PMID- 28418551
TI - Cost-Effectiveness of Sacubitril-Valsartan in Patients Who Have Heart Failure
With Reduced Ejection Fraction.
PMID- 28418552
TI - Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and
Consideration for Organ Donation.
PMID- 28418553
TI - Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and
Consideration for Organ Donation.
PMID- 28418554
TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
PMID- 28418555
TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
PMID- 28418556
TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
PMID- 28418557
TI - A Strong and Simple Heart.
PMID- 28418558
TI - Lectures on Inhumanity: Teaching Medical Ethics in German Medical Schools Under
Nazism.
AB - Nazi medicine and its atrocities have been explored in depth over the past few
decades, but scholars have started to examine medical ethics under Nazism only in
recent years. Given the medical crimes and immoral conduct of physicians during
the Third Reich, it is often assumed that Nazi medical authorities spurned
ethics. However, in 1939, Germany introduced mandatory lectures on ethics as part
of the medical curriculum. Course catalogs and archival sources show that
lectures on ethics were an integral part of the medical curriculum in Germany
between 1939 and 1945. Nazi officials established lecturer positions for the new
subject area, named Medical Law and Professional Studies, at every medical
school. The appointed lecturers were mostly early members of the Nazi Party and
imparted Nazi political and moral values in their teaching. These values included
the unequal worth of human beings, the moral imperative of preserving a pure
Aryan people, the authoritarian role of the physician, the individual's
obligation to stay healthy, and the priority of public health over individual
patient care. This article shows that there existed not only a Nazi version of
medical ethics but also a systematic teaching of such ethics to students in Nazi
Germany. The findings illustrate that, from a historical point of view, the
notion of "eternal values" that are inherent to the medical profession is
questionable. Rather, the prevailing medical ethos can be strongly determined by
politics and the zeitgeist and therefore has to be repeatedly negotiated.
PMID- 28418559
TI - Web Exclusives. Annals for Hospitalists Inpatient Notes - Human Factors
Engineering and Inpatient Care-New Ways to Solve Old Problems.
PMID- 28418560
TI - Web Exclusives. Annals Consult Guys - Like Pulling Teeth: Antiplatelet Therapy in
the Dental Office.
PMID- 28418563
TI - Tensile Mechanical Properties and Dynamic Collagen Fiber Re-Alignment of the
Murine Cervix are Dramatically Altered Throughout Pregnancy.
AB - The cervix is a unique organ able to dramatically change its shape and function
by serving as a physical barrier for the growing fetus and then undergoing
dramatic dilation allowing for delivery of a term infant. As a result, the cervix
endures changing mechanical forces from the growing fetus. There is an emerging
concept that the cervix may change or remodel "early" in many cases of
spontaneous preterm birth (sPTB). However, the mechanical role of the cervix in
both normal and preterm birth remains unclear. Therefore, the primary objective
of this study was to determine the mechanical and structural responses of murine
cervical tissue throughout a normal gestational time course. In this study, both
tissue structural and material properties were determined via a quasi-static
tensile load-to-failure test, while simultaneously obtaining dynamic collagen
fiber re-alignment via cross-polarization imaging. This study demonstrated that
the majority of the mechanical properties evaluated decreased at midgestation and
not just at term, while collagen fiber re-alignment occurred earlier in the
loading curve for cervices at term. This suggests that although structural
changes in the cervix occur throughout gestation, the differences in material
properties function in combination with collagen fiber re-alignment as mechanical
precursors to regulate term gestation. This work lays a foundation for
investigating cervical biomechanics and the role of the cervix in preterm birth.
PMID- 28418564
TI - Ultra Wide-Field Laser Scanning Imaging of an Unusually Bullous Retinoschisis:
Retinoschisis vs Detachment.
PMID- 28418565
TI - Familial Exudative Vitreoretinopathy.
PMID- 28418566
TI - Peripheral Exudative Hemorrhagic Chorioretinopathy.
PMID- 28418567
TI - Serpiginous Choroiditis.
PMID- 28418571
TI - Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant
Exposure: A Systematic Review and Meta-analysis.
AB - Importance: Several studies have examined the links between prenatal exposure to
antidepressants and autism spectrum disorders (ASDs) in children, with
inconsistent results, especially regarding the impact of the trimester of
exposure. Objective: To perform a systematic review of the literature and a meta
analysis of published studies to assess the association between ASDs and fetal
exposure to antidepressants during pregnancy for each trimester of pregnancy and
preconception. Data Sources: PubMed, EMBASE, and PsycINFO databases up to May
2016 were searched in June 2016 for observational studies. For the meta-analyses,
data were analyzed on RevMan version 5.2 using a random-effect model. For the
review, studies were included if they had been published and were cohort or case
control studies, and for the meta-analysis, studies were included if they were
published studies and the data were not derived from the same cohorts. Study
Selection: We included all the studies that examined the association between ASDs
and antenatal exposure to antidepressants. Data Extraction and Synthesis: Three
reviewers independently screened titles and abstracts, read full-text articles,
and extracted data. The quality of the studies was also assessed. Main Outcomes
and Measures: Primary outcome was the association between antidepressants during
pregnancy and ASDs. Secondary outcomes were the associations between
antidepressants in each individual trimester or before pregnancy and ASDs.
Results: Our literature search identified 10 relevant studies with inconsistent
results. For prenatal exposure, the meta-analysis on the 6 case-control studies
(117 737 patients) evidenced a positive association between antidepressant
exposure and ASDs (odds ratio [OR], 1.81; 95% CI, 1.49-2.20). The association was
weaker when controlled for past maternal mental illness (OR, 1.52; 95% CI, 1.09
2.12). A similar pattern was found whatever the trimester of exposure considered
(first trimester: OR, 2.09, 95% CI,1.66-2.64; second: OR, 2.00, 95% CI, 1.55
2.59; and third: OR, 1.90, 95% CI, 1.20-3.02. Controlled for past maternal mental
illness: first trimester: OR, 1.79; 95% CI, 1.27-2.52, second: OR, 1.67, 95% CI,
1.14-2.45; and third: OR, 1.54, 95% CI, 0.82-2.90). No association was found when
the 2 cohort studies were pooled (772 331 patients) for the whole pregnancy
(hazard ratio, 1.26; 95% CI, 0.91-1.74) or for the first trimester. In addition,
preconception exposure to antidepressants was significantly associated with an
increased risk for ASDs (OR controlled for past maternal illness, 1.77; 95% CI,
1.49-2.09). Conclusions and Relevance: There is a significant association between
increased ASD risk and maternal use of antidepressants during pregnancy; however,
it appears to be more consistent during the preconception period than during each
trimester. Maternal psychiatric disorders in treatment before pregnancy rather
than antenatal exposure to antidepressants could have a major role in the risk
for ASDs. Future studies should address the problem of this potential confounder.
PMID- 28418572
TI - The Single High-Sensitivity Serum Cardiac Troponin T Level: A Significant Advance
for Chest Pain Pathways?
PMID- 28418573
TI - Trends in Surgical Management and Costs for Operative Treatment of Proximal
Humerus Fractures in the Elderly.
AB - Proximal humerus fractures in the elderly are increasing in frequency as the
population ages. The purpose of this study was to investigate surgical and cost
trends in the Medicare population. The PearlDiver database was queried using
diagnosis codes to identify Medicare recipients with proximal humerus fractures
from 2005 to 2012. Surgical trends, demographics, and charge/reimbursement data
were analyzed. There were 750,426 proximal humerus fractures in Medicare
recipients during the 8-year period. Eighty-five percent of the fractures were
treated nonoperatively; however, the percentage of operative vs nonoperative
management increased significantly over time for all fractures, isolated
fractures, and fracture dislocations. Open reduction and internal fixation (ORIF)
was the most common surgical treatment and remained constant. Reverse total
shoulder arthroplasty (RTSA) increased by 406% and hemiarthroplasty (HEMI)
decreased by 47%. Compared with younger patients, older patients were more likely
to undergo HEMI or RTSA than to undergo ORIF for isolated fractures and fracture
dislocations. Charges and reimbursements from Medicare increased over time. The
charge to reimbursement gap increased from 87% in 2005 to 104% in 2012. Charges
were higher for RTSA than for ORIF or HEMI. Nonoperative management was the
treatment of choice for 85% of proximal humerus fractures in the elderly;
however, there was a trend toward higher rates of surgery. The RTSA rate
increased and the HEMI rate decreased, while ORIF remained constant. There was an
increasing charge to reimbursement ratio for all procedure types. [Orthopedics.
2017; 40(4):e641-e647.].
PMID- 28418574
TI - Inadequacy of Joint Aspiration for Detection of Persistent Periprosthetic
Infection During Two-Stage Septic Revision Knee Surgery.
AB - Despite the lack of validation, synovial aspiration remains a common practice
during 2-stage septic revision total knee arthroplasty (TKA). The goal of this
study was to investigate the diagnostic validity of synovial
polymethylmethacrylate (PMMA) spacer aspiration of temporary knee arthrodesis to
detect persistent periprosthetic joint infection before TKA reimplantation. This
retrospective cohort study included 73 consecutive patients who underwent 2-stage
septic revision TKA according to a standard protocol. After explantation surgery,
including temporary arthrodesis with an intramedullary stabilized PMMA spacer,
all patients had synovial aspiration 2 weeks before reimplantation to exclude
persistent periprosthetic joint infection. Patients had a 2-week antibiotic
holiday before aspiration. Sensitivity and specificity of the synovial PMMA
spacer joint aspiration for the detection of periprosthetic joint infection were
determined and referenced against intraoperative microbiologic and histologic
samples obtained at second-stage surgery. Sensitivity of the synovial PMMA spacer
aspiration was 21%. Because of poor diagnostic validity, synovial PMMA spacer
aspiration cannot be recommended for routine exclusion of persistent
periprosthetic joint infection before TKA reimplantation. Therefore, exclusion of
persistent periprosthetic joint infection should be supplemented by other
diagnostic methods, and it is not necessary to delay TKA reimplantation for PMMA
spacer aspiration. [Orthopedics. 2017; 40(4):231-234.].
PMID- 28418575
TI - Effects of Previous Osteotomy on Outcome of Hip Resurfacing Arthroplasty.
AB - The effect of previous conservative surgeries on the outcome of metal-on-metal
hip resurfacing arthroplasty (HRA) has not been studied. This study compared
postoperative clinical scores and survivorship results of hips with and without
previous osteotomies in a population of patients who underwent HRA. A total of
1101 patients (1375 hips) with a mean age of 51.3 years at the time of surgery
underwent HRA at a single center. Sixty-nine patients had undergone prior surgery
on the operated hip including 14 osteotomies (1 pelvic, 6 femoral, and 7 combined
pelvic and femoral osteotomies). Mean follow-up was comparable for patients with
prior osteotomy and patients in the control group (101 months vs 96 months,
P=.6916); however, patients with prior osteotomies were much younger at the time
of surgery (34 years vs 51 years, P=.0001). Kaplan-Meier survival estimates were
calculated, and the Cox proportional hazard ratio was used to adjust for the
covariates that differed between the 2 groups and affected the survivorship of
hip resurfacing. Patients who underwent prior osteotomy showed lower pain and
activity scores. In addition, patients who underwent prior osteotomy had a
greater chance of revision than the rest of the cohort (hazard ratio, 3.87; 95%
confidence interval, 1.54-9.68; P=.004). For patients in whom the natural anatomy
or the bone quality of the hip has been severely altered by a prior osteotomy,
HRA may be contraindicated if good component fixation cannot be achieved and hip
biomechanics restored. [Orthopedics. 2017; 40(4):e609-e616.].
PMID- 28418576
TI - The "Safe Zone" Technique Improves Suture Placement and Accuracy During
Arthroscopic Remplissage.
AB - In response to recent concerns about the accuracy of suture passage during
arthroscopic remplissage, this study was conducted to determine whether a
previously described "safe zone" technique can improve the accuracy of suture
passage. A recommended safe zone technique was used for arthroscopic remplissage
on 6 cadaveric specimens. The safe zone was described as a region at least 1 cm
lateral and no greater than 3 cm distal to the posterolateral acromion. Results
were compared with a control group of 6 specimens for which the safe zone
technique was not used. For each group, 24 suture passes were performed. In the
safe zone group, 83.3% (20 of 24) of sutures passed through the infraspinatus
tendon. This was a significant improvement compared with the control group, in
which only 25% (6 of 24) of sutures pierced the infraspinatus tendon (P<.01). In
the safe zone group, 4.2% (1 of 24) of attempted suture passes were placed
through the muscle or musculotendinous junction compared with 75% (18 of 24) in
the control group (P<.01). Prevention of overmedialization improved significantly
with the safe zone technique. In the safe zone group, both anchors had
significantly more lateral (6 to 10 mm) suture passage compared with the control
group (P<.01). The safe zone technique also showed greater precision of suture
passes, and overall precision (SD) improved in 75% of passes. The safe zone
technique significantly improved the accuracy of suture penetration into the
infraspinatus tendon during arthroscopic remplissage. This reproducible method
may help to prevent the reported complications of remplissage. [Orthopedics.
2017; 40(4):e598-e603.].
PMID- 28418577
TI - Prospective Assessment of Sleep Quality Before and After Primary Total Joint
Replacement.
AB - Sleep disruption is a common, yet rarely addressed, complaint among patients who
have undergone total joint arthroplasty (TJA). This study assessed sleep quality
before and after primary TJA. A total of 105 patients who underwent primary total
hip arthroplasty (THA) or total knee arthroplasty (TKA) prospectively completed
questionnaires during the preoperative, early postoperative, and late
postoperative periods. The survey included the Epworth Sleepiness Scale, current
sleeping habits, and patient perspectives of sleep quality and duration. In the
early postoperative period (4.7+/-2.0 weeks), patients reported significant
increases in sleep disturbance as denoted by increased length of time to fall
asleep (P=.006) and mean nightly awakenings (P=.002) compared with the
preoperative baseline. At late postoperative follow-up (40.8+/-19.5 weeks),
patients' sleep quality subsequently improved above the preoperative baseline.
Approximately 40% of patients tried a new sleeping method postoperatively, the
most common being new pillow placement. No significant differences in pre- or
postoperative sleeping trends were noted between THA and TKA patients. These
findings suggest transient sleep disturbance is common in the early postoperative
period, with subsequent improvement by 10-month follow-up after a primary TJA.
Given the growing importance of patient satisfaction in health care systems,
orthopedic surgeons must manage patients' expectations while working with them to
optimize sleep quality after TJA. A multimodal approach with preoperative
counseling, early postoperative sleep modifications, and possibly preemptive use
of medications may improve transient sleep disturbance among TJA patients.
[Orthopedics. 2017; 40(4):e636-e640.].
PMID- 28418579
TI - ?
PMID- 28418578
TI - ?
PMID- 28418580
TI - Effect of surfactant species and electrophoretic medium composition on the
electrophoretic behavior of neutral and water-insoluble linear synthetic polymers
in nonaqueous capillary zone electrophoresis.
AB - We have recently demonstrated the separation of neutral and water-insoluble
linear synthetic polymers in nonaqueous capillary zone electrophoresis (NACZE)
using a cationic surfactant of cetyltrimethylammonium chloride (CTAC). In this
study, eight ionic surfactants were investigated for the separation of four
synthetic polymers (polystyrene, polymethylmethacrylates, polybutadiene, and
polycarbonate); only three surfactants (CTAC, dimethyldioctadecylammonium
bromide, and sodium dodecylsulfate) caused their separation. The order of the
interaction between the polymers and the surfactants depended on both the
surfactant species and the composition of the electrophoretic medium. Their
investigation revealed that the separation is majorly affected by the hydrophobic
interactions between the polymers and the ionic surfactants. In addition, the
electrophoretic behavior of polycarbonate suggested that electrostatic
interaction also affects the selectivity of the polymers.
PMID- 28418581
TI - Leaf rust infection reduces herbivore-induced volatile emission in black poplar
and attracts a generalist herbivore.
AB - Plants release complex volatile blends after separate attack by herbivores and
pathogens, which play many roles in interactions with other organisms. Large
perennials are often attacked by multiple enemies, but the effect of combined
attacks on volatile emission is rarely studied, particularly in trees. We
infested Populus nigra trees with a pathogen, the rust fungus Melampsora larici
populina, and Lymantria dispar caterpillars alone and in combination. We
investigated poplar volatile emission and its regulation, as well as the behavior
of the caterpillars towards volatiles from rust-infected and uninfected trees.
Both the rust fungus and the caterpillars alone induced volatile emission from
poplar trees. However, the herbivore-induced volatile emission was significantly
reduced when trees were under combined attack by the herbivore and the fungus.
Herbivory induced terpene synthase transcripts as well as jasmonate
concentrations, but these increases were suppressed when the tree was
additionally infected with rust. Caterpillars preferred volatiles from rust
infected over uninfected trees. Our results suggest a defense hormone crosstalk
upon combined herbivore-pathogen attack in poplar trees which results in lowered
emission of herbivore-induced volatiles. This influences the preference of
herbivores, and might have other far-reaching consequences for the insect and
pathogen communities in natural poplar forests.
PMID- 28418582
TI - COP1 conveys warm temperature information to hypocotyl thermomorphogenesis.
AB - Plants adjust their architecture to optimize growth and reproductive success
under changing climates. Hypocotyl elongation is a pivotal morphogenic trait that
is profoundly influenced by light and temperature conditions. While hypocotyl
photomorphogenesis has been well characterized at the molecular level, molecular
mechanisms underlying hypocotyl thermomorphogenesis remains elusive. Here, we
demonstrate that the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1)
conveys warm temperature signals to hypocotyl thermomorphogenesis. To investigate
the roles of COP1 and its target ELONGATED HYPOCOTYL 5 (HY5) during hypocotyl
thermomorphogenesis, we employed Arabidopsis mutants that are defective in their
genes. Transgenic plants overexpressing the genes were also produced. We examined
hypocotyl growth and thermoresponsive turnover rate of HY5 protein at warm
temperatures under both light and dark conditions. Elevated temperatures trigger
the nuclear import of COP1, thereby alleviating the suppression of hypocotyl
growth by HY5. While the thermal induction of hypocotyl growth is circadian
gated, the degradation of HY5 by COP1 is uncoupled from light responses and
timing information. We propose that thermal activation of COP1 enables
coincidence between warm temperature signaling and circadian rhythms, which
allows plants to gate hypocotyl thermomorphogenesis at the most profitable time
at warm temperatures.
PMID- 28418583
TI - Lung cancer-A global perspective.
AB - Lung cancer is the leading cause of cancer deaths worldwide. While tobacco
exposure is responsible for the majority of lung cancers, the incidence of lung
cancer in never smokers, especially Asian women, is increasing. There is a global
variation in lung cancer biology with EGFR mutations being more common in Asian
patients, while Kras mutation is more common in Caucasians. This review will
focus on the global variations in lung cancer and its treatment.
PMID- 28418584
TI - Transforming growth factor beta-inhibitor Repsox downregulates collagen
expression of scleroderma dermal fibroblasts and prevents bleomycin-induced mice
skin fibrosis.
AB - Inhibition of transforming growth factor (TGF)-beta1 signalling may be one of the
most reliable approaches to treat skin fibrosis of scleroderma. Although there
have been many basic researches of TGF-beta blockade reagents, few of them were
proved to have inhibitory effects on fibrosis both in vitro and in vivo. In this
study, we randomly chose four commercially available low molecular weight
compounds (Repsox, LY2109761, LY364947 and K02288) from TGF-beta1 inhibitor
library, and compared their antifibrotic effects in vitro and in vivo. We
demonstrated that Repsox has the most potent inhibitory effects on TGF-beta
induced expression of CTGF and collagen of cultured normal dermal fibroblasts in
vitro and their constitutive overexpression of scleroderma fibroblast in vitro.
In addition, Repsox could attenuate skin fibrosis by bleomycin in vivo, via the
downregulation of CTGF or collagen. Our results may facilitate clinical trial of
Repsox against fibrotic diseases in future.
PMID- 28418585
TI - miR-128-1 is not required for hair pigmentation in mice.
AB - MicroRNAs are endogenous, regulatory RNAs implicated in many biological processes
including pigmentation. Software algorithms and in vitro experiments predict that
microRNAs can target pigmentation pathway genes, but few have been tested in
vivo. MiR-128-1, a microRNA within the strongly selected lactase locus in the
human genome, has predicted pigmentation targets. To test the role of miR-128-1
in pigment regulation, we created C57BL/6 agouti miR-128-1 knockout mice and
quantified melanin deposition in hair. MiR-128-1 knockout mice have no detectable
hair pigmentation phenotype. We conclude that miR-128-1 does not play a
significant regulatory role in hair pigmentation in mice.
PMID- 28418586
TI - Simulated presence therapy for dementia.
AB - BACKGROUND: Dementia is a common and serious neuropsychiatric syndrome,
characterised by progressive cognitive and functional decline. The majority of
people with dementia develop behavioural disturbances, also known as behavioural
and psychological symptoms of dementia (BPSD). Several non-pharmacological
interventions have been evaluated to treat BPSD in people with dementia.
Simulated presence therapy (SPT), an intervention that uses video or audiotape
recordings of family members played to the person with dementia, is a possible
approach to treat BPSD. OBJECTIVES: To assess the effects of SPT on behavioural
and psychological symptoms and quality of life in people with dementia. SEARCH
METHODS: We searched ALOIS (the Specialised Register of the Cochrane Dementia and
Cognitive Improvement Group), CENTRAL (The Cochrane Library) (9 February 2016),
MEDLINE Ovid SP (1946 to 6 January 2017), Embase Ovid SP (1972 to 6 January
2017), PsycINFO Ovid SP (1806 to 6 January 2017), CINAHL via EBSCOhost (1980 to 6
January 2017), LILACS via BIREME (all dates to 6 January 2017),
ClinicalTrials.gov (ClinicalTrials.gov) (all dates to 6 January 2017), and the
World Health Organization (WHO) Portal (apps.who.int/trialsearch) (all dates to 6
January 2017). We also checked the reference lists of relevant articles to
identify any additional studies. SELECTION CRITERIA: Randomised and quasi
randomised controlled trials, including cross-over studies, that evaluated the
efficacy of SPT, consisting of personalised audio or videotape recordings of
family members, in people with any form of dementia. DATA COLLECTION AND
ANALYSIS: Two authors independently selected studies, assessed risk of bias and
extracted data. No meta-analyses were conducted because of substantial
heterogeneity among the included studies. MAIN RESULTS: Three trials with 144
participants met the inclusion criteria. Two of the trials had a randomised cross
over design, one was a cross-over trial which we classified as quasi
randomised.Participants in the included studies were people with dementia living
in nursing homes. They were predominantly women and had a mean age of over 80
years. SPT was performed using an audio or video recording prepared by family
members or surrogates. It varied in its content, frequency of administration and
duration. All the studies compared multiple treatments. In one study, SPT was
compared with two other interventions; in the other two studies, it was compared
with three other interventions. Specifically, SPT was compared to usual care,
personalised music (two studies), a 'placebo' audiotape containing the voice of a
person (two studies), and one-to-one social interaction performed by trained
research assistants (one study). In terms of outcomes evaluated, one study
considered agitation and withdrawn behaviour (both assessed with three methods);
the second study evaluated verbal disruptive behaviour (assessed with three
methods); and the third study evaluated physically agitated behaviour and
verbally agitated behaviour (the method used was not clearly described).According
to the GRADE criteria, the overall quality of the evidence was very low due to
very small numbers of participants and risk of bias in the included studies;
(none of the trials was at low risk of selection bias; all the trials were at
high risk of performance bias; one trial was at high risk of attrition bias; and
all had unclear selective reporting).Because of variation in the participants,
the format of SPT, the comparison interventions, and the measures used to assess
outcomes, we judged the results unsuitable for a meta-analysis.Within each trial,
the effect of SPT on behaviour, compared to usual care, was mixed and depended on
the measure used. Two trials which included a personalised music intervention
reported no significant differences between simulated presence and music on
behavioural outcomes. Because the overall quality of the evidence was very low,
we were very uncertain regarding all the resultsNone of the studies evaluated
quality of life or any of our secondary outcome measures (performance of
activities of daily living, dropout and carer burden). AUTHORS' CONCLUSIONS: We
were unable to draw any conclusions about the efficacy of SPT for treating
behavioural and psychological symptoms and improving quality of life of people
with dementia. New high-quality studies are needed to investigate the effect of
SPT.
PMID- 28418587
TI - Short Syntheses of 4-Deoxycarbazomycin B, Sorazolon E, and (+)-Sorazolon E2.
AB - Short syntheses of 4-deoxycarbazomycin B and sorazolon E were established through
the condensation of cyclohexanone and commercially available 4-methoxy-2,3
dimethylaniline, followed by PdII -catalyzed dehydrogenative
aromatization/intramolecular C-C bond coupling and deprotection. A chiral
dinuclear vanadium complex (Ra ,S,S)-6 mediated the enantioselective oxidative
coupling of sorazolon E, affording (+)-sorazolon E2 in good enantioselectivity.
PMID- 28418588
TI - Intracellular ROS levels determine the apoptotic potential of keratinocyte by
Quantum Dot via blockade of AKT Phosphorylation.
AB - Quantum dots (QDs) have shown great potential for biomedical use in a broad range
including diagnostic agents. However, the regulatory mechanism of dermal toxicity
is poorly understood. In this study, we investigated how QDs-induced apoptosis is
regulated in human keratinocytes. We also examined the effect of carboxylic acid
coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and
apoptosis-related cellular signalling. The viability of keratinocyte was
inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS
production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT
dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3
and caspases-9 was significantly increased. We also found that a decrease in
cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the
abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis.
Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and
AKT-dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic
potential in the human skin equivalent model (HSEM). These data show that QD
induced intracellular ROS levels may be an important parameter in QD-induced
apoptosis. These findings from this study indicate that intracellular ROS levels
might determine the apoptotic potential of keratinocyte by QD via blockade of AKT
phosphorylation.
PMID- 28418589
TI - A distinct cutaneous microbiota profile in autoimmune bullous disease patients.
AB - Bullous pemphigoid (BP) is the most common autoimmune blistering disease in
Europe. As both the incidence of the disease and the relative proportion of the
elderly population continue to rise, it represents a significant medical burden.
Whereas some progress has been achieved in defining genetic risk factors for
autoimmune blistering diseases, no environmental agent has been conclusively
identified. Emerging evidence suggests that host immunity may influence the skin
microbiota, while the latter modulates cutaneous immunity. Nevertheless, the
relationship between skin microbial communities and autoimmune bullous disease
has yet to be studied in humans. Here, we aim to characterise and compare the
skin microbiome of patients with BP and healthy, age-matched controls at numerous
body sites. Similar to what has been shown in healthy controls, the composition
of skin microbiota in patients with BP appears to be very divergent and site
specific. Microbial phylum abundances differ between perilesional sites of
patients with BP and the same anatomic locations of control patients. A distinct
cutaneous microbiota profile, which correlates with BP, further strengthens the
significance of commensal-host interaction on our immune system. Moreover, these
results raise the possibility that the cutaneous microbiome may contribute to the
pathogenesis of BP, with important implications for the treatment of this
disease.
PMID- 28418590
TI - Control of biofouling by xanthine oxidase on seawater reverse osmosis membranes
from a desalination plant: enzyme production and screening of bacterial isolates
from the full-scale plant.
AB - : Control of biofouling on seawater reverse osmosis (SWRO) membranes is a major
challenge as treatments can be expensive, damage the membrane material and often
biocides do not remove the polymers in which bacteria are embedded. Biological
control has been largely ignored for biofouling control. The objective of this
study was to demonstrate the effectiveness of xanthine oxidase enzyme against
complex fouling communities and then identify naturally occurring bacterial
strains that produce the free radical generating enzyme. Initially, 64 bacterial
strains were isolated from different locations of the Perth Seawater Desalination
Plant. In our preceding study, 25/64 isolates were selected from the culture
collection as models for biofouling studies, based on their prevalence in
comparison to the genomic bacterial community. In this study, screening of these
model strains was performed using a nitroblue tetrazolium assay in the presence
of hypoxanthine as substrate. Enzyme activity was measured by absorbance. Nine of
25 strains tested positive for xanthine oxidase production, of which
Exiguobacterium from sand filters and Microbacterium from RO membranes exhibited
significant levels of enzyme production. Other genera that produced xanthine
oxidase were Marinomonas, Pseudomonas, Bacillus, Pseudoalteromonas and
Staphylococcus. Strain variations were observed between members of the genera
Microbacterium and Bacillus. SIGNIFICANCE AND IMPACT OF THE STUDY: Xanthine
oxidase, an oxidoreductase enzyme that generates reactive oxygen species, is
endogenously produced by many bacterial species. In this study, production of the
enzyme by bacterial isolates from a full-scale desalination plant was
investigated for potential use as biological control of membrane fouling in
seawater desalination. We have previously demonstrated that free radicals
generated by a commercially available xanthine oxidase in the presence of a
hypoxanthine substrate, effectively dispersed biofilm polysaccharides on
industrially fouled membranes. Bacterial xanthine oxidase production in the
presence of hypoxanthine may prove to be a cost effective, in situ method for
alleviation of fouling.
PMID- 28418591
TI - A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused
by SLURP1 deficiency.
AB - Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar
keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully
recapitulates the human disease, with increased keratinocyte proliferation and
thickening of the epidermis on the volar surface of the paws. There has long been
speculation that SLURP1 serves as a ligand for a receptor that regulates
keratinocyte growth and differentiation. We were intrigued that mutations leading
to increased signalling through the epidermal growth factor receptor (EGFR) cause
PPK. Here, we sought to determine whether reducing EGFR signalling would
ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we
bred Slurp1-deficient mice that were homozygous for a hypomorphic Egfr allele.
The hypomorphic Egfr allele, which leads to reduced EGFR signalling in
keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency,
suggesting that SLURP1 deficiency causes PPK independently (or downstream) from
the EGFR pathway.
PMID- 28418592
TI - From the Editors.
PMID- 28418593
TI - Nonparametric Tree-Based Predictive Modeling of Storm Outages on an Electric
Distribution Network.
AB - This article compares two nonparametric tree-based models, quantile regression
forests (QRF) and Bayesian additive regression trees (BART), for predicting storm
outages on an electric distribution network in Connecticut, USA. We evaluated
point estimates and prediction intervals of outage predictions for both models
using high-resolution weather, infrastructure, and land use data for 89 storm
events (including hurricanes, blizzards, and thunderstorms). We found that
spatially BART predicted more accurate point estimates than QRF. However, QRF
produced better prediction intervals for high spatial resolutions (2-km grid
cells and towns), while BART predictions aggregated to coarser resolutions
(divisions and service territory) more effectively. We also found that the
predictive accuracy was dependent on the season (e.g., tree-leaf condition, storm
characteristics), and that the predictions were most accurate for winter storms.
Given the merits of each individual model, we suggest that BART and QRF be
implemented together to show the complete picture of a storm's potential impact
on the electric distribution network, which would allow for a utility to make
better decisions about allocating prestorm resources.
PMID- 28418594
TI - Massive crab recruitment events to the shallow subtidal zone.
PMID- 28418595
TI - Validation of PAGE-B model in Asian chronic hepatitis B patients receiving
entecavir or tenofovir.
AB - BACKGROUND & AIMS: A new hepatocellular carcinoma risk prediction model, PAGE-B,
which includes age, gender and platelet count as constituent variables, has
recently been proposed in Caucasian chronic hepatitis B patients. We validated
PAGE-B model and compared its accuracy with that of conventional risk prediction
models in Asian chronic hepatitis B patients. METHODS: Chronic hepatitis B
patients treated with entecavir or tenofovir were consecutively recruited. The
performance of PAGE-B and three conventional risk prediction models (CU-HCC, GAG
HCC and REACH-B) were analysed. RESULTS: A total of 1092 chronic hepatitis B
patients (668 men, 61.2%) were selected between August 2006 and January 2015. The
mean age was 48 years. During the follow-up period (median, 43.6 months), 36
(3.3%) patients developed hepatocellular carcinoma. Older age (hazard ratio
[HR]=1.077), male gender (HR=3.676) and lower platelet count (HR=0.984) were
independent predictors of hepatocellular carcinoma development. The PAGE-B showed
similar area under receiver operating characteristic curves (AUROCs) to GAG-HCC
and CU-HCC at 3 years (0.777 vs 0.793 and 0.743, respectively; all P>.05) and 5
years (0.799 vs 0.803 and 0.744, respectively; all P>.05), whereas the AUROCs of
PAGE-B were significantly higher than those of the REACH-B (0.602 at 3 years and
0.572 at 5 years, P<.05). CONCLUSIONS: Our study demonstrated that PAGE-B is
applicable to Asian chronic hepatitis B patients receiving ETV or TDF therapy.
The PAGE-B showed similar predictive performance to GAG-HCC and CU-HCC.
PMID- 28418596
TI - Hair follicle dermal stem cells and skin-derived precursor cells: Exciting tools
for endogenous and exogenous therapies.
AB - Understanding the cellular interactions and molecular signals underlying hair
follicle (HF) regeneration may have significant implications for restorative
therapies for skin disease that diminish hair growth, whilst also serving to
provide fundamental insight into the mechanisms underlying adult tissue
regeneration. One of the major, yet underappreciated, players in this process is
the underlying HF mesenchyme. Here, we provide an overview of a mesenchymal
progenitor pool referred to as hair follicle dermal stem cells (hfDSCs), discuss
their potential functions within the skin and their relationship to skin-derived
precursors (SKPs), and consider unanswered questions about the function of these
specialized fibroblasts. We contend that dermal stem cells provide an important
reservoir of renewable dermal progenitors that may enable development of novel
restorative therapies following hair loss, skin injury or disease.
PMID- 28418597
TI - Mid-trimester residual cervical length and the risk of preterm birth in
pregnancies after abdominal radical trachelectomy: a retrospective analysis.
AB - OBJECTIVE: To investigate the association between mid-trimester residual cervical
length (CL) and the risk of preterm birth in pregnancies after abdominal radical
trachelectomy (RT). DESIGN: Retrospective cohort study. SETTING: University
hospital. POPULATION: A total of 33 deliveries after 22 weeks' gestation in 30
women who underwent abdominal RT including prophylactic cervical cerclage and
perinatal care between January 2002 and May 2016. METHODS: The association
between mid-trimester residual CL (the distance between the cerclage and the
external cervical os) and gestational age at delivery was investigated. Receiver
operating characteristics (ROC) curve analysis was performed to estimate the
optimal cut-off values of the mid-trimester residual CL for the prediction of
preterm birth. MAIN OUTCOME MEASURES: Preterm birth before 34 weeks' gestation.
RESULTS: Mid-trimester residual CL showed a significant correlation with
gestational age at delivery (r = 0.36, P < 0.05). There was a significant
difference in residual CL between women who did and those who did not give birth
before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good
predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of
75%, positive predictive value of 55% and negative predictive value of 86% (area
under ROC curve, 0.75). CONCLUSIONS: Mid-trimester residual CL is significantly
correlated with gestational age at delivery. Residual CL assessment could be used
to reassure physicians and women that there is only a small chance of preterm
birth in pregnancies after abdominal RT. TWEETABLE ABSTRACT: Mid-trimester
residual cervical length is a good predictor of preterm birth after radical
trachelectomy.
PMID- 28418598
TI - Redox-Disproportionation of a Decamethyltitanocene(III) Isonitrile Alkynyl
Complex.
AB - A mixed decamethyltitanocene(III) isonitrile alkynyl complex (7) was synthesized
by the sequential introduction of the isonitrile and alkynyl ligands. Direct
synthesis results in the formation of the diamagnetic decamethyltitanocene
bis(isonitrile) (2) and bis(alkynyl) (3) complexes. Compound 7 undergoes
disproportionation at room temperature to give 2 and 3. All complexes were fully
characterized by IR, NMR, and EPR spectroscopy, and mass spectrometry. Molecular
structures for complexes 2 and 7 are reported. The stability and reactivity of
these complexes are rationalized by DFT computations.
PMID- 28418599
TI - Use of the Harmonic scalpel for Delorme's procedure.
AB - AIM: There are many surgical techniques that deal with external rectal prolapse
but perineal procedures have the advantage of reduced invasiveness. Therefore,
despite concerns regarding high recurrence rates, the technique is still used by
many surgeons. METHOD: This manuscript and video describe our early clinical
experience using the Harmonic scalpel in 11 consecutive patients who underwent a
Delorme's procedure for external rectal prolapse. RESULTS: The median age of
patients was 76 (range: 30-94) years. There were no intra-operative
complications, and the median operative time was 78 min. Intra-operative blood
loss was minimal (mean 45 ml; range 20-70 ml). Median length of stay was 2
(range: 0-8) days. Overall morbidity and recurrence were both 18%, with a median
follow-up of 15 (range: 1-23) months. Nine patients were operated on by a senior
trainee with consultant supervision. CONCLUSION: The advantages of this device
are mainly those of ease of mucosal dissection, minimal blood loss and shorter
operative time in comparison with published series.
PMID- 28418600
TI - Validation of a laboratory-developed test of human sperm capacitation.
AB - Sperm must undergo capacitation to become fertilization competent. Here we
validated that monosialotetrahexosylganglioside (GM1 ) localization patterns,
which were assessed in the Cap-ScoreTM Sperm Function Test, reflect a capacitated
state in human sperm. First, we defined patterns representing sperm that do or do
not respond to stimuli for capacitation. Sperm with "capacitated" patterns had
exposed acrosomal carbohydrates and underwent acrosome exocytosis in response to
calcium ionophore (A23187). Precision was evaluated by percent change of the Cap
Score measured for 50, 100, 150, and 200 sperm. Changes of 11%, 6%, and 5% were
observed (n >= 23); therefore, we counted >=150 sperm per condition. Variance
within and between readers was evaluated using 20 stitched image files generated
from unique ejaculates. Two trained readers randomly resampled each image 20
times, reporting an average standard deviation of 3 Cap-Score units and
coefficient of variation of 13% when rescoring samples, with no difference
between readers. Semen liquefaction times <=2 hr and mechanical liquefaction with
Pasteur or wide-orifice transfer pipettes did not alter Cap-Score values.
However, liquefaction with chymotrypsin (p = 0.002) and bromelain (p = 0.049)
reduced response to capacitating stimuli and induced membrane damage, while
counterintuitively improving sperm motility. Together, these data validate the
Cap-Score assay for the intended purpose of providing information on sperm
capacitation and male fertility. In addition to its clinical utility as a
diagnostic tool, this test of sperm function can reveal the impact of common
practices of semen handling on the ability of sperm to respond to capacitation
stimuli.
PMID- 28418601
TI - Two arginine residues in the COOH-terminal of human beta-defensin-3 constitute an
essential motif for antimicrobial activity and IL-6 production.
AB - Human beta-defensin-3 (HBD-3) possesses antimicrobial activities and the
potential to induce proinflammatory cytokines. HBD-3 contains a unique motif of
two arginine residues (Arg or R) in the COOH-terminal region. To understand the
bioactive properties of the Arg residues of HBD-3, we examined antimicrobial
activities against Staphylococcus aureus and Pseudomonas aeruginosa using
synthetic HBD-2, HBD-3 and two variant peptides of HBD-3: the Arg-truncated
variant designated desR HBD-3 and NRR HBD-3, in which both Arg residues were
shifted to the N-terminal region. IL-6 production from keratinocytes was studied
using the peptides. HBD-3 possessed approximately five-fold more potent
antimicrobial activities, evaluated as the minimum inhibitory concentration
(MIC), against S. aureus compared with desR and NRR HBD-3, while no significant
activity was observed in HBD-2. The antimicrobial activity of HBD-3 against S.
aureus was well preserved even at high sodium chloride concentrations, but was
attenuated in desR and NRR HBD-3. All the peptides exhibited similar
antimicrobial activities against P. aeruginosa, but HBD-2 and desR HBD-3 showed
diminished antimicrobial activities against P. aeruginosa at high salt
concentrations. IL-6 production was significantly induced in keratinocytes with
HBD-3, but not remarkably with stimulation by other peptide. These Arg residues
are essential for the antimicrobial and biological properties of HBD-3.
PMID- 28418602
TI - Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in
psoriasis skin.
AB - Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane
receptors with key functions in canonical Wnt signalling. Wnt ligands are thought
to play an important role in innate immunity and psoriasis, and recent studies
assigned LRP5/6 anti-inflammatory properties. The objective of this study was to
investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in
peripheral blood and in mononuclear cells of patients with chronic plaque type
psoriasis compared with control individuals. To investigate the effect of UV-B
radiation, LRP5/6 skin gene expression was analysed before and after narrowband
UV-B treatment. Our results showed significantly decreased gene expression of
LRP5 and LRP6 in lesional skin and in peripheral blood from patients with
psoriasis compared with non-lesional skin and healthy control skin.
Immunohistochemistry did not reveal differences in protein expression of LRP5/6.
Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene
expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin
and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in
psoriasis.
PMID- 28418603
TI - Towards Quantitative Systems Pharmacology Models of Chemotherapy-Induced
Neutropenia.
AB - Neutropenia is a serious toxic complication of chemotherapeutic treatment. For
years, mathematical models have been developed to better predict hematological
outcomes during chemotherapy in both the traditional pharmaceutical sciences and
mathematical biology disciplines. An increasing number of quantitative systems
pharmacology (QSP) models that combine systems approaches, physiology, and
pharmacokinetics/pharmacodynamics have been successfully developed. Here, I
detail the shift towards QSP efforts, emphasizing the importance of incorporating
systems-level physiological considerations in pharmacometrics.
PMID- 28418605
TI - The G534E variant in HABP2 is not associated with increased risk of familial
nonmedullary thyroid cancer in Brazilian Kindreds.
PMID- 28418604
TI - Loss of INK4a/Arf gene enhances ultraviolet radiation-induced cutaneous tumor
development.
AB - The CDKN2A locus encodes for tumor suppressor genes p16INK4a and p14Arf which are
frequently inactivated in human skin tumors. The purpose of this study was to
determine the relationship between loss of INK4a/Arf activity and inflammation in
the development of ultraviolet (UV) radiation-induced skin tumors. Panels of
INK4a/Arf-/- mice and wild-type (WT) mice were treated with a single dose of UVB
(200 mJ/cm2 ). For long-term studies, these mice were irradiated with UVB (200
mJ/cm2 ) three times weekly for 30 weeks. At the end of the experiment, tissues
were harvested from mice and assayed for inflammatory biomarkers and cytokines. A
single dose of UVB resulted in a significant increase in reactive oxygen species
(ROS) and 8-dihydroxyguanosine (8-oxo-dG) lesions in INK4a/Arf-/- mice compared
to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf-/-
mice had tumors, whereas there were no tumors in WT controls after 24 weeks of
UVB exposure. The increase in tumor development correlated with a significant
increase in nuclear factor (NF)-kappaB, cyclooxygenase-2 (COX-2), prostaglandin
E2 (PGE2 ) and its receptors both in UVB-exposed skin and in the tumors. A
significant increase was seen in inflammatory cytokines in skin samples of
INK4a/Arf-/- mice following treatment with chronic UVB radiation. Furthermore,
significantly more CD11b+ Gr1+ myeloid cells were present in UVB-exposed
INK4a/Arf-/- mice compared to WT mice. Our data indicate that by targeting UVB
induced inflammation, it may be possible to prevent UVB-induced skin tumors in
individuals that carry CDKN2A mutation.
PMID- 28418606
TI - Nationwide incidence of blindness in South Korea: a 12-year study from 2002 to
2013.
AB - IMPORTANCE: Blindness is an important public health issue. BACKGROUND: The
background of the study is to determine the incidence of blindness in South
Korea. DESIGN: Nationwide population-based retrospective study. PARTICIPANTS: All
individuals from South Korea (n = 47 516 098). METHODS: Patients confirmed with
legal blindness based on the worse-seeing and better-seeing eyes between 1
January 2002 and 31 December 2013 were included. The Korean National Health
Insurance Service (KNHIS) database was used. Using the World Health Organization
definition, blindness was defined as best-corrected visual acuity in the worse
seeing and better-seeing eyes of <20/400. The mean incidence of blindness during
the 12-year period was estimated. The population of South Korea was estimated
using census data in 2005 and 2010. MAIN OUTCOME MEASURES: The total number of
legal blindness cases in the KNHIS database. RESULTS: We identified 195 004 and
20 492 cases of newly developed legal blindness based on the worse-seeing and
better-seeing eyes, respectively, and the mean incidences of blindness were 34.2
and 3.6 cases/100 000 person-years, respectively. The prevalence of blindness
based on the worse-seeing and better-seeing eyes was 425.3 and 57.7 cases/100 000
persons, respectively. The incidence of blindness based on the worse-seeing eye
was higher in men than in women overall. Additionally, the incidence increased
with age and showed a decreasing trend from 2002 to 2013. CONCLUSIONS AND
RELEVANCE: The prevalence of blindness showed an increasing trend from 2002 to
2013. The findings of our study will help in the assessment of the blindness
related socio-economic burden and in healthcare planning.
PMID- 28418607
TI - Current trends in quantitative proteomics - an update.
AB - Proteins can provide insights into biological processes at the functional level,
so they are very promising biomarker candidates. The quantification of proteins
in biological samples has been routinely used for the diagnosis of diseases and
monitoring the treatment. Although large-scale protein quantification in complex
samples is still a challenging task, a great amount of effort has been made to
advance the technologies that enable quantitative proteomics. Seven years ago, in
2009, we wrote an article about the current trends in quantitative proteomics. In
writing this current paper, we realized that, today, we have an even wider
selection of potential tools for quantitative proteomics. These tools include new
derivatization reagents, novel sampling formats, new types of analyzers and
scanning techniques, and recently developed software to assist in assay
development and data analysis. In this review article, we will discuss these
innovative methods, and their current and potential applications in proteomics.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28418608
TI - Methods for the isolation and 3D culture of dermal papilla cells from human hair
follicles.
AB - The dermal papilla is a cluster of mesenchymal cells located at the base of the
hair follicle which have a number of important roles in the regulation of hair
growth. As a consequence, in vitro models of these cells are widely used to study
the molecular mechanisms which underlie hair follicle induction, growth and
maintenance. While dermal papilla from rodent hair follicles can be digested
prior to cell isolation, the unique extracellular matrix composition found in
human dermal papilla renders enzymes such as trypsin and collagenase insufficient
for digestion of the dermal papilla into a single cell suspension. As such, to
grow human dermal papilla cells in vitro, the papilla has to first be isolated
via a micro-dissection approach from the follicle. In this article we describe
the micro-dissection and culture methods, which we use within our laboratory, for
the study of human dermal papilla cells.
PMID- 28418609
TI - Real-time measurement of needle forces and acute pressure changes during
intravitreal injections.
AB - BACKGROUND: The purpose of this study was to use a physiological pressure
transducer to measure real-time, continuous pressure changes in an ex vivo study
model of porcine eyes to record the amount of force needed for scleral
penetration and to measure acute intraocular pressure rise during intravitreal
injections. METHODS: A pressure transducer was inserted into the anterior chamber
of 30 fresh porcine eyes, and intraocular pressure was measured 2 s prior to
intravitreal injection until 2 s after. A force transducer plate was used to
insert various gauge needles into the vitreous cavity and the amount of force in
Newtons (N) required for scleral penetration was recorded. RESULTS: For scleral
perforation, 32- and 30-gauge needles required 0.44 N and 0.45 N, significantly
less than larger gauge needles (P < 0.05). Similarly, 27- and 25-gauge needles
required more force than smaller gauge needles but less than 19 gauge (P < 0.05).
Intraocular pressure increased an average of 64.5 mmHg during intravitreal
injection. Two seconds postinjection intraocular pressure readings showed a
residual intraocular pressure increase of 11.1 mmHg from pre-injection baseline.
CONCLUSION: Real-time continuous recordings of pressure reveal that an
instantaneous intraocular pressure spike occurs during intravitreal injection and
appears to be separate from the intraocular pressure spike that occurs during
needle insertion. This pressure spike is transient and has not been captured by
previous methods of intraocular pressure measurement, which rely on single time
point measurements. The clinical significance of this brief intraocular pressure
spike is unclear and warrants further investigation.
PMID- 28418610
TI - Localization patterns of the ganglioside GM1 in human sperm are indicative of
male fertility and independent of traditional semen measures.
AB - Semen analysis lacks a functional component and best identifies extreme cases of
infertility. The ganglioside GM1 is known to have functional roles during
capacitation and acrosome exocytosis. Here, we assessed whether GM1 localization
patterns (Cap-ScoreTM) correspond with male fertility in different settings:
Study 1 involved couples pursuing assisted reproduction in a tertiary care
fertility clinic, while Study 2 involved men with known fertility versus those
questioning their fertility at a local urology center. In Study 1, we examined
various thresholds versus clinical history for 42 patients; 13 had Cap-Scores
>=39.5%, with 12 of these (92.3%) achieving clinical pregnancy by natural
conception or <=3 intrauterine insemination cycles. Of the 29 patients scoring
<39.5%, only six (20.7%) attained clinical pregnancy by natural conception or <=3
intrauterine insemination cycles. In Study 2, Cap-Scores were obtained from 76
fertile men (Cohort 1, pregnant partner or recent father) and compared to 122 men
seeking fertility assessment (Cohort 2). Cap-Score values were normally
distributed in Cohort 1, with 13.2% having Cap-Scores more than one standard
deviation below the mean (35.3 +/- 7.7%). Significantly, more men in Cohort 2 had
Cap-Scores greater than one standard deviation below the normal mean (33.6%; p =
0.001). Minimal/no relationship was found between Cap-Score and sperm
concentration, morphology, or motility. Together, these data demonstrate that Cap
Score provides novel, clinically relevant insights into sperm function and male
fertility that complement traditional semen analysis. Furthermore, the data
provide normal reference ranges for fertile men that can help clinicians counsel
couples toward the most appropriate fertility treatment.
PMID- 28418611
TI - Ectopic expression of the transcription factor MafB in basal keratinocytes
induces hyperproliferation and perturbs epidermal homeostasis.
AB - Mammalian epidermis is composed of four morphologically and functionally distinct
layers of keratinocytes. The innermost basal layer consists of proliferating self
renewing keratinocytes, which also undergo asymmetric cell division to
differentiate into postmitotic suprabasal cells throughout life. Control of the
balance between growth and differentiation of basal cells is important for
epidermal homeostasis to prevent skin disorders including malignancies; however,
the underlying mechanism remains to be elucidated. Recently, MafB was identified
as one of the transcription factors that regulate epidermal keratinocyte
differentiation. MafB is expressed in postmitotic differentiating keratinocytes,
and epidermal differentiation is partially impaired in MafB-deficient mice. To
further establish the roles of MafB in the epidermis in vivo, we generated mice
transgenic for MafB under the control of the basal cell-specific keratin (Krt) 14
promoter. In the epidermis of transgenic mice at embryonic day 18.5, the number
of proliferating Krt14-positive basal-like cells was increased, and the granular
and cornified layers were thickened. Furthermore, these MafB transgenic mice
developed papillomas spontaneously with age. Therefore, MafB promotes
differentiation in postmitotic keratinocytes and simultaneously has potential to
promote growth when ectopically expressed in undifferentiated basal
keratinocytes.
PMID- 28418612
TI - An efficient and enantioselective Michael addition of aromatic oximes to
alpha,beta-unsaturated aldehydes promoted by a chiral diamine catalyst derived
from alpha,alpha-diphenyl prolinol.
AB - Chiral diamine catalysts 11a-e derived from alpha,alpha-diphenyl prolinol were
prepared and successfully applied to the Michael addition of aromatic oximes to
alpha,beta-unsaturated aldehydes in mediocre to good yields (up to 78%) and good
to high enantioselectivities (up to 93% ee).
PMID- 28418613
TI - Complement-independent blistering mechanisms in bullous pemphigoid.
AB - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that
clinically demonstrates tense blisters with widespread erythema, histologically
demonstrates subepidermal blistering and immunologically demonstrates the
presence of circulating autoantibodies against hemidesmosomal molecules.
Complement activation has long been regarded as necessary for the generation of
the BP. However, certain evidence has recently come to support non-complemental
blistering mechanisms. The story of BP blistering mechanisms is a complicated
one. This review mainly focuses on a specific blistering mechanism that
highlights the role of complements in BP blistering.
PMID- 28418614
TI - Efficacy and safety of low-dose heparin in hemodialysis.
AB - INTRODUCTION: The dose of unfractionated heparin (UFH) administered during
hemodialysis (HD) varies widely. This prospective study evaluated the safety and
efficacy of UFH dose de-escalation. METHODS: Sixty-six prevalent patients on HD
receiving UFH per standard-dose protocol (load dose [LD] 50-75 units/kg,
maintenance dose [MD] 500-1000 units/hour) had heparin prescription converted to
low-dose protocol (start LD 15 units/kg and MD 500 units/hour; dose adjusted in
small increments based on assessments of extracorporeal blood circuit).
Coagulation parameters, dialysis adequacy, dialyzer clotting, anemia management,
and dialyzer reuse rates were compared based on the heparin protocol. FINDINGS:
Mean(SD) UFH dose per HD session, before and after protocol conversion, was
6178(2644) and 2913(1116) units, respectively (P < 0.0001). This corresponded to
LD 52.1(16.6) units/kg and MD 615(207) units/hour with standard-dose protocol,
and LD 18.3(6.5) units/kg and MD 505(27) units/hour with low-dose protocol (P <
0.0001). Mid and postdialysis aPTT was 55.3(31.2) and 35.1(7.8) seconds before,
and 37.3(12.9) and 31.5(5.3) seconds after conversion (P = 0.007 and 0.003,
respectively); no significant changes in D-dimer levels occurred. Low-dose UFH
was associated with a small increase in URR and spKt/V (73.0 and 1.54) compared
with dialysis clearance on standard-dose UFH (71.2 and 1.48, respectively, P =
0.02). Weekly dose of ESA decreased by 2388 units postconversion (P = 0.03),
while hemoglobin levels and the weekly dose of intravenous iron did not change (P
= 0.16 and 0.78). A small rise in the rate of moderate dialyzer clotting at the
end of HD was noted with low-dose UFH (5.7% vs. 7.5%, P = 0.002); the rate of
severe dialyzer clotting events did not change (P = 0.91). No change in the
dialyzer reuse rate was noted (18.5 vs. 17.0 treatments, P = 0.26). DISCUSSION:
Low-dose heparinization did not compromise dialysis adequacy and permitted ESA
dose reduction. Our findings suggest that in prevalent patients on HD, UFH dose
of 15-20 units/kg loading and 500 units/hour maintenance was medically safe and
effective.
PMID- 28418616
TI - Communicating the health effects of indoor exposure to particulate matter.
PMID- 28418615
TI - Co-expression of GR79 EPSPS and GAT yields herbicide-resistant cotton with low
glyphosate residues.
AB - Glyphosate-resistant (GR) crops have been adopted on a massive scale by North and
South American farmers. Currently, about 80% of the 120 million hectares of the
global genetically modified (GM) crops are GR crop varieties. However, the
adoption of GR plants in China has not occurred at the same pace, owing to
several factors including, among other things, labour markets and the residual
effects of glyphosate in transgenic plants. Here, we report the co-expression of
codon-optimized forms of GR79 EPSPS and N-acetyltransferase (GAT) genes in
cotton. We found five times more resistance to glyphosate with 10-fold reduction
in glyphosate residues in two pGR79 EPSPS-pGAT co-expression cotton lines, GGCO2
and GGCO5. The GGCO2 line was used in a hybridization programme to develop new GR
cottons. Field trials at five locations during three growing seasons showed that
pGR79-pGAT transgenic cotton lines have the same agronomic performance as
conventional varieties, but were USD 390-495 cheaper to produce per hectare
because of the high cost of conventional weed management practices. Our strategy
to pyramid these genes clearly worked and thus offers attractive promise for the
engineering and breeding of highly resistant low-glyphosate-residue cotton
varieties.
PMID- 28418617
TI - Improved survival of patients with hepatocellular carcinoma and compensated
hepatitis C virus-related cirrhosis who attained sustained virological response.
AB - BACKGROUND: Few studies examined the outcome of patients with hepatitis C virus
(HCV)-related cirrhosis who developed hepatocellular carcinoma (HCC). The
relative weight as determinant of death for cancer vs end-stage liver disease
(ESLD) and the benefit of HCV eradication remain undefined. This multicentre,
retrospective analysis evaluates overall survival (OS), rate of decompensation
and tumour recurrence in compensated HCC patients treated with interferon (IFN)
according to HCV status since HCC diagnosis. METHODS: Two groups of patients with
HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated
cirrhotics with prior sustained virological response (SVR) on IFN-based regimens
(N=19); (ii) compensated cirrhotics without SVR (viraemic) (N=156). RESULTS: Over
a median follow-up of 3.0 years since the onset of HCC, OS was longer for HCC
patients with SVR than for viraemic patients (log-rank P=.004). The 5-year OS
rate was 65.9% in patients with SVR vs 31.9% in viraemic patients. Similar trends
were reported for hepatic decompensation (log-rank P=.01) and tumour recurrence
(log-rank P=.01). These findings were confirmed at multivariable and propensity
score analysis. At propensity analysis, 0/19 compensated patients with SVR died
for ESLD vs 7/19 (37%) viraemic patients (P=.004). HCC mortality was similar in
the two groups. CONCLUSIONS: Hepatocellular carcinoma patients with prior SVR and
compensated cirrhosis at the time of tumour diagnosis have prolonged OS than
viraemic patients. Given the lack of cirrhosis progression, no SVR patient
ultimately died for ESLD while this condition appears the main cause of death
among viraemic patients.
PMID- 28418619
TI - Determination of lipoic acid in human urine by capillary zone electrophoresis.
AB - Fast, simple, and accurate CE method enabling determination of lipoic acid (LA)
in human urine has been developed and validated. LA is a disulfide-containing
natural compound absorbed from the organism's diet. Due to powerful antioxidant
activity, LA has been used for prevention and treatment of various diseases and
disorders, e.g. cardiovascular diseases, neurodegenerative disorders, and cancer.
The proposed analytical procedure consists of liquid-liquid sample extraction,
reduction of LA with tris(2-carboxyethyl)phosphine, derivatization with 1-benzyl
2-chloropyridinium bromide (BCPB) followed by field amplified sample injection
stacking, capillary zone electrophoresis separation, and ultraviolet-absorbance
detection of LA-BCPB derivative at 322 nm. Effective baseline electrophoretic
separation was achieved within 6 min under the separation voltage of 20 kV (~80
MUA) using a standard fused-silica capillary (effective length 51.5 cm, 75 MUm
id) and BGE consisted of 0.05 mol/L borate buffer adjusted to pH 9. The
experimentally determined limit of detection for LA in urine was 1.2 MUmol/L. The
calibration curve obtained for LA in urine showed linearity in the range 2.5-80
MUmol/L, with R2 0.9998. The relative standard deviation of the points of the
calibration curve was lower than 10%. The analytical procedure was successfully
applied to analysis of real urine samples from seven healthy volunteers who
received single 100 mg dose of LA.
PMID- 28418618
TI - Investigation of Arsenotrophic Microbiome in Arsenic-Affected Bangladesh
Groundwater.
AB - Arsenotrophic bacteria contribute to the nutrient cycling in arsenic (As)
affected groundwater. This study employed a culture-independent and -dependent
investigation of arsenotrophic microbiomes in As affected groundwater samples
collected from Madhabpur, Sonatengra, and Union Porishod in Singair Upazila,
Manikganj, Bangladesh. Total As contents, detected by Atomic Absorption
Spectrophotometry (AAS) of the samples, were 47 ug/L (Madhabpur, SNGW-1), 53 ug/L
(Sonatengra, SNGW-2), and 12 ug/L (Union porishod, SNGW-3), whereas the control
well (SNGW-4; depths >150 m) showed As content of 6 ug/L. Denaturing Gradient Gel
Electrophoresis (DGGE) analysis of the amplified 16S rRNA gene from As-affected
groundwater samples revealed the dominance of aerobic bacteria Pseudomonas within
heterogeneous bacterial populations. DGGE of heterotrophic enrichments
supplemented with arsenite [As (III)] for 4 weeks showed the dominance of
Chryseobacterium, Flavobacterium, and Aquabacterium, whereas the dominant genera
in that of autotrophic enrichments were Aeromonas, Acinetobacter, and
Pseudomonas. Cultured bacteria retrieved from both autotrophic and heterotrophic
enrichments were distinguished into nine genotypes belonging to Chryseobacterium,
Acinetobacter, Escherichia, Pseudomonas, Stenotrophomonas, Janibacter,
Staphylococcus, and Bacillus. They exhibited varying range of As(III) tolerance
from 4 to 27 mM. As(III) transformation potential was confirmed within the
isolates with oxidation rate as high as 0.143 mM/h for Pseudomonas sp. Sn 28. The
arsenotrophic microbiome specifies their potential role in groundwater As-cycling
and their genetic information provide the scientific basis for As-bioremediation.
PMID- 28418621
TI - Issue Information-Declaration of Helsinki.
PMID- 28418620
TI - Fast and Highly Sensitive Ionic-Polymer-Gated WS2 -Graphene Photodetectors.
AB - The combination of graphene with semiconductor materials in heterostructure
photodetectors enables amplified detection of femtowatt light signals using
micrometer-scale electronic devices. Presently, long-lived charge traps limit the
speed of such detectors, and impractical strategies, e.g., the use of large gate
voltage pulses, have been employed to achieve bandwidths suitable for
applications such as video-frame-rate imaging. Here, atomically thin graphene-WS2
heterostructure photodetectors encapsulated in an ionic polymer are reported,
which are uniquely able to operate at bandwidths up to 1.5 kHz whilst maintaining
internal gain as large as 106 . Highly mobile ions and the nanometer-scale Debye
length of the ionic polymer are used to screen charge traps and tune the Fermi
level of the graphene over an unprecedented range at the interface with WS2 .
Responsivity R = 106 A W-1 and detectivity D* = 3.8 * 1011 Jones are observed,
approaching that of single-photon counters. The combination of both high
responsivity and fast response times makes these photodetectors suitable for
video-frame-rate imaging applications.
PMID- 28418622
TI - Newborn Length of Stay and Risk of Readmission.
AB - BACKGROUND: Evidence on the association between newborn length of hospital stay
(LOS) and risk of readmission is conflicting. We compared methods for modelling
this relationship, by gestational age, using population-level hospital data on
births in England between 2005-14. METHODS: The association between LOS and
unplanned readmission within 30 days of postnatal discharge was explored using
four approaches: (i) modelling hospital-level LOS and readmission rates; (ii)
comparing trends over time in LOS and readmission; (iii) modelling individual LOS
and adjusted risk of readmission; and (iv) instrumental variable analyses
(hospital-level mean LOS and number of births on the same day). RESULTS: Of 4 667
827 babies, 5.2% were readmitted within 30 days. Aggregated data showed hospitals
with longer mean LOS were not associated with lower readmission rates for vaginal
(adjusted risk ratio (aRR) 0.87, 95% confidence interval (CI) 0.66, 1.13), or
caesarean (aRR 0.89, 95% CI 0.72, 1.12) births. LOS fell by an average 2.0% per
year for vaginal births and 3.4% for caesarean births, while readmission rates
increased by 4.4 and 5.1% per year respectively. Approaches (iii) and (iv)
indicated that longer LOS was associated with a reduced risk of readmission, but
only for late preterm, vaginal births (34-36 completed weeks' gestation).
CONCLUSIONS: Longer newborn LOS may benefit late preterm babies, possibly due to
increased medical or psychosocial support for those at greater risk of
potentially preventable readmissions after birth. Research based on observational
data to evaluate relationships between LOS and readmission should use methods to
reduce the impact of unmeasured confounding.
PMID- 28418623
TI - An efficient method for gene knock-down by RNA interference in human skin mast
cells.
AB - Mast cells (MCs) from human skin have been notoriously resistant to gene
manipulation, and a method to knock-down gene expression in in situ
differentiated MCs is highly desired. The Dharmacon Accell(r) transfection system
proved successful on several "difficult-to-transfect" cells. In the present work,
we therefore tested this method on skin-derived MCs using different siRNA
entities. The siRNA was readily taken up, followed by pronounced, specific
reduction of gene and protein expression. Hence, we present the first efficient
technique for the manipulation of gene expression in primary skin MCs ex vivo,
which combines high transfection rates with retained cell viability.
PMID- 28418624
TI - Nickel-Cornered Molecular Rectangles as Polycyclic Aromatic Hydrocarbon
Receptors.
AB - Two nickel-cornered organometallic metalla-rectangles containing a pyrene-linked
di-N-heterocyclic carbene have been prepared. The dimensions of one side of the
rectangle were modulated by either using pyrazine or 4,4'-bipyridine. The two
molecules were tested as hosts for the recognition of seven small polycyclic
aromatic hydrocarbons (PAHs) in [D6 ]acetone. By using 1 H NMR spectroscopy
titrations, it could be established that the host-guest stoichiometries of the
inclusion complexes formed were 1:1 for the pyrazine-based host, and 1:2 for the
host containing bipyridine, in accordance with the larger dimensions of the
latter. The molecular structure of the inclusion complex consisting of the
bipyridine-containing host and pyrene was determined by X-ray crystallography,
which confirms the 1:2 host-guest stoichiometry of this species. The
determination of the association constants indicate that the binding strengths
are in the order:
Perylene= C10 is required to maintain the base-pairing
discrimination of thymidine between G and A. The results from our molecular
dynamics simulations show that in the T:G-pair-containing duplex, the geranyl and
farnesyl groups fit into the minor groove and stabilize the overall duplex
stability. This effect cannot be achieved by the shorter carbon chains such as
methyl and dimethylallyl groups. For a duplex containing a T:A pair, the terpene
groups disrupt both hydrogen bonding and stacking interactions by pushing the
opposite A out of the helical structure. Overall, as the terpene chain length
increases, the xT:G pair stabilizes the duplex, whereas the xT:A pair causes
destabilization, indicating the evolutionary significance of the long terpene
group on base-pairing specificity and codon recognition.
PMID- 28418650
TI - Zinc Ion Coordinated Poly(Ionic Liquid) Antimicrobial Membranes for Wound
Healing.
AB - Herein, a series of quaternary ammonium (Qa) or imidazolium (Im) cation-based
poly(ionic liquid) (PIL) membranes and their corresponding zinc ion coordinated
PIL membranes were synthesized. The effects of chemical structure, including
organic cations, alkyl side chain of substitution, and zinc atoms on the
antimicrobial activities against Escherichia coli, Staphylococcus aureus, and
Candida albicans were investigated. The Zn-containing PIL membranes show higher
antibacterial activities compared to those of pristine PIL membranes due to the
synergistic attributes of both organic cations (Qa or Im) and zinc atoms. A wound
healing test using methicillin-resistant S. aureus infected mouse as the model
further demonstrated that zinc ion coordinated PIL membranes were antibacterially
active, biologically safe, and may have potential application as an antimicrobial
wound dressing in a clinical setting.
PMID- 28418651
TI - Electrodeposition of Highly Porous Pt Nanoparticles Studied by Quantitative 3D
Electron Tomography: Influence of Growth Mechanisms and Potential Cycling on the
Active Surface Area.
AB - Nanoporous Pt nanoparticles (NPs) are promising fuel cell catalysts due to their
large surface area and increased electrocatalytic activity toward the oxygen
reduction reaction (ORR). Herein, we report on the influence of the growth
mechanisms on the surface properties of electrodeposited Pt dendritic NPs with
large surface areas. The electrochemically active surface was studied by hydrogen
underpotential deposition (H UPD) and compared for the first time to high-angle
annular dark field scanning transmission electron microscopy (HAADF-STEM)
quantitative 3D electron tomography of individual nanoparticles. Large nucleation
overpotential leads to a large surface coverage of roughened spheroids, which
provide a large roughness factor (Rf) but low mass-specific electrochemically
active surface area (EASA). Lowering the nucleation overpotential leads to highly
porous Pt NPs with pores stretching to the center of the structure. At the
expense of smaller Rf, the obtained EASA values of these structures are in the
range of those of large surface area supported fuel cell catalysts. The active
surface area of the Pt dendritic NPs was measured by electron tomography, and it
was found that the potential cycling in the H adsorption/desorption and Pt
oxidation/reduction region, which is generally performed to determine the EASA,
leads to a significant reduction of that surface area due to a partial collapse
of their dendritic and porous morphology. Interestingly, the extrapolation of the
microscopic tomography results in macroscopic electrochemical parameters
indicates that the surface properties measured by H UPD are comparable to the
values measured on individual NPs by electron tomography after the degradation
caused by the H UPD measurement. These results highlight that the combination of
electrochemical and quantitative 3D surface analysis techniques is essential to
provide insights into the surface properties, the electrochemical stability, and,
hence, the applicability of these materials. Moreover, it indicates that care
must be taken with widely used electrochemical methods of surface area
determination, especially in the case of large surface area and possibly unstable
nanostructures, since the measured surface can be strongly affected by the
measurement itself.
PMID- 28418653
TI - Synthesis and Biological Evaluation of the First Triple Inhibitors of Human
Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA
Phosphodiesterase 2 (Tdp2).
AB - Tdp1 and Tdp2 are two tyrosyl-DNA phosphodiesterases that can repair damaged DNA
resulting from topoisomerase inhibitors and a variety of other DNA-damaging
agents. Both Tdp1 and Tdp2 inhibition could hypothetically potentiate the
cytotoxicities of topoisomerase inhibitors. This study reports the successful
structure-based design and synthesis of new 7-azaindenoisoquinolines that act as
triple inhibitors of Top1, Tdp1, and Tdp2. Enzyme inhibitory data and
cytotoxicity data from human cancer cell cultures establish that modification of
the lactam side chain of the 7-azaindenoisoquinolines can modulate their
inhibitory potencies and selectivities vs Top1, Tdp1, and Tdp2. Molecular
modeling of selected target compounds bound to Top1, Tdp1, and Tdp2 was used to
design the inhibitors and facilitate the structure-activity relationship
analysis. The monitoring of DNA damage by gamma-H2AX foci formation in human
PBMCs (lymphocytes) and acute lymphoblastic leukemia CCRF-CEM cells documented
significantly more DNA damage in the cancer cells vs normal cells.
PMID- 28418652
TI - Design and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown
Like Oxotricyclic Core as the P2-Ligand To Combat Multidrug-Resistant HIV
Variants.
AB - Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1
protease inhibitors are reported. Inhibitor 5 displayed superior antiviral
activity and drug-resistance profiles. In fact, this inhibitor showed several
orders of magnitude improved antiviral activity over the FDA approved drug
darunavir. This inhibitor incorporates an unprecedented 6-5-5 ring-fused crown
like tetrahydropyranofuran as the P2 ligand and an aminobenzothiazole as the P2'
ligand with the (R)-hydroxyethylsulfonamide isostere. The crown-like P2 ligand
for this inhibitor has been synthesized efficiently in an optically active form
using a chiral Diels-Alder catalyst providing a key intermediate in high
enantiomeric purity. Two high resolution X-ray structures of inhibitor-bound HIV
1 protease revealed extensive interactions with the backbone atoms of HIV-1
protease and provided molecular insight into the binding properties of these new
inhibitors.
PMID- 28418654
TI - A Robust and Accurate Tight-Binding Quantum Chemical Method for Structures,
Vibrational Frequencies, and Noncovalent Interactions of Large Molecular Systems
Parametrized for All spd-Block Elements (Z = 1-86).
AB - We propose a novel, special purpose semiempirical tight binding (TB) method for
the calculation of structures, vibrational frequencies, and noncovalent
interactions of large molecular systems with 1000 or more atoms. The functional
form of the method is related to the self-consistent density functional TB scheme
and mostly avoids element-pair-specific parameters. The parametrization covers
all spd-block elements and the lanthanides up to Z = 86 using reference data at
the hybrid density functional theory level. Key features of the Hamiltonian are
the use of partially polarized Gaussian-type orbitals, a double-zeta orbital
basis for hydrogen, atomic-shell charges, diagonal third-order charge
fluctuations, coordination number-dependent energy levels, a noncovalent halogen
bond potential, and the well-established D3 dispersion correction. The accuracy
of the method, called Geometry, Frequency, Noncovalent, eXtended TB (GFN-xTB), is
extensively benchmarked for various systems in comparison with existing
semiempirical approaches, and the method is applied to a few representative
structural problems in chemistry.
PMID- 28418655
TI - Accuracy Test of the OPLS-AA Force Field for Calculating Free Energies of Mixing
and Comparison with PAC-MAC.
AB - We have calculated the excess free energy of mixing of 1053 binary mixtures with
the OPLS-AA force field using two different methods: thermodynamic integration
(TI) of molecular dynamics simulations and the Pair Configuration to Molecular
Activity Coefficient (PAC-MAC) method. PAC-MAC is a force field based quasi
chemical method for predicting miscibility properties of various binary mixtures.
The TI calculations yield a root mean squared error (RMSE) compared to
experimental data of 0.132 kBT (0.37 kJ/mol). PAC-MAC shows a RMSE of 0.151 kBT
with a calculation speed being potentially 1.0 * 104 times greater than TI. OPLS
AA force field parameters are optimized using PAC-MAC based on vapor-liquid
equilibrium data, instead of enthalpies of vaporization or densities. The RMSE of
PAC-MAC is reduced to 0.099 kBT by optimizing 50 force field parameters. The
resulting OPLS-PM force field has a comparable accuracy as the OPLS-AA force
field in the calculation of mixing free energies using TI.
PMID- 28418656
TI - Informing the Selection of Screening Hit Series with in Silico Absorption,
Distribution, Metabolism, Excretion, and Toxicity Profiles.
AB - High-throughput screening (HTS) has enabled millions of compounds to be assessed
for biological activity, but challenges remain in the prioritization of hit
series. While biological, absorption, distribution, metabolism, excretion, and
toxicity (ADMET), purity, and structural data are routinely used to select
chemical matter for further follow-up, the scarcity of historical ADMET data for
screening hits limits our understanding of early hit compounds. Herein, we
describe a process that utilizes a battery of in-house quantitative structure
activity relationship (QSAR) models to generate in silico ADMET profiles for hit
series to enable more complete characterizations of HTS chemical matter. These
profiles allow teams to quickly assess hit series for desirable ADMET properties
or suspected liabilities that may require significant optimization. Accordingly,
these in silico data can direct ADMET experimentation and profoundly impact the
progression of hit series. Several prospective examples are presented to
substantiate the value of this approach.
PMID- 28418657
TI - Oil-in-Water Emulsions Stabilized by Saponified Epoxidized Soybean Oil-Grafted
Hydroxyethyl Cellulose.
AB - An oil-in-water emulsion stabilized by saponified epoxidized soybean oil-grafted
hydroxyethyl cellulose (H-ESO-HEC) was investigated. By using an ultrasonic
method, oil-in-water emulsions were prepared by blending 50 wt % soybean oil and
50 wt % H-ESO-HEC aqueous suspensions. The influence of H-ESO-HEC concentrations
on the properties of oil-in-water emulsions was examined. The H-ESO-HEC
concentrations in the aqueous phase varied from 0.02 to 0.40 wt %. When the H-ESO
HEC concentration was 0.4 wt %, the emulsion remained stable for >80 days. The
mean droplet sizes of the emulsions decreased by increasing the H-ESO-HEC
concentration and extending the ultrasonic time. The adsorption amounts of H-ESO
HEC at the oil-water interface increased when the H-ESO-HEC concentrations in the
aqueous phase increased. The rheological property revealed that the apparent
viscosity of the H-ESO-HEC-stabilized oil-in-water emulsions increased when the H
ESO-HEC concentrations increased. Steady flow curves indicated an interfacial
film formation in the emulsions. The evolution of G', G", and tan eta indicated
the predominantly elastic behaviors of all the emulsions.
PMID- 28418658
TI - Cp*Rh(III)/Bicyclic Olefin Cocatalyzed C-H Bond Amidation by Intramolecular Amide
Transfer.
AB - A bicyclic olefin was discovered as a cocatalyst in a Cp*Rh(III)-catalyzed C-H
bond amidation proceeding by an intramolecular amide transfer in N
phenoxyacetamide derivatives. Combining experimental and theoretical studies, we
propose that the olefin promotes a Rh(III) intermediate to undergo oxidative
addition into the O-N bond to form a Rh(V) nitrenoid species and subsequently
direct the nitrenoid to add to the ortho position. The amide directing group
plays a dual role as a cleavable coordinating moiety as well as an essential
coupling partner for the C-H amidation. This methodology was successfully applied
to the late-stage diversification of natural products and a marketed drug under
mild conditions.
PMID- 28418659
TI - Microbial Cell Factories for the Production of Terpenoid Flavor and Fragrance
Compounds.
AB - Terpenoid flavor and fragrance compounds are of high interest to the aroma
industry. Microbial production offers an alternative sustainable access to the
desired terpenoids independent of natural sources. Genetically engineered
microorganisms can be used to synthesize terpenoids from cheap and renewable
resources. Due to its modular architecture, terpenoid biosynthesis is especially
well suited for the microbial cell factory concept: a platform host engineered
for a high flux toward the central C5 prenyl diphosphate precursors enables the
production of a broad range of target terpenoids just by varying the pathway
modules converting the C5 intermediates to the product of interest. In this
review typical terpenoid flavor and fragrance compounds marketed or under
development by biotech and aroma companies are given, and the specificities of
the aroma market are discussed. The main part of this work focuses on key
strategies and recent advances to engineer microbes to become efficient terpenoid
producers.
PMID- 28418660
TI - PEGylated Solanesol for Oral Delivery of Coenzyme Q10.
AB - Coenzyme Q10 (CoQ10) is widely used in preventive or curative treatment of
cardiovascular diseases. However, CoQ10 exhibits an extremely low solubility in
aqueous medium as well as a poor oral bioavailability. Therefore, solanesyl
poly(ethylene glycol) succinate (SPGS) and CoQ10 were formulated as CoQ10-SPGS
micelles with a high content of CoQ10 to improve the bioavailability of CoQ10 in
rat. Findings indicate that, in the CoQ10-SPGS micelles, SPGS is self-assembled
into stable nanosized micelles with a CoQ10 loading capacity of more than 39%.
The CoQ10-SPGS micelles exhibit an enhanced photostability upon exposure to
simulated sunlight. In vivo experiments demonstrate that, as compared to that of
the coarse suspensions of CoQ10, there was three-fold enhancement of oral
bioavailability for CoQ10-loaded SPGS micelles depending on varying molecular
weight of SPGS. In the encapsulation of CoQ10 by SPGS micelles, the self
assembled nanocarriers with strong muco-adhesive properties lead to increases in
the solubility and oral absorption of lipophilic CoQ10 nanoparticles.
PMID- 28418662
TI - Partial in Situ Reduction of Copper(II) Resulting in One-Pot Formation of 2D
Neutral and 3D Cationic Copper(I) Iodide-Pyrazine Coordination Polymers:
Structure and Emissive Properties.
AB - On the way to copper(I) iodide coordination polymers with specific luminescent
properties, the in situ reduction of Cu(II) in the presence of KI and bidentate N
heteroatomic ligand, either pyrazine (pyz) or 4,4'-bipyridine (bpy), resulted in
one two-dimensional and two three-dimensional new coordination networks. Starting
from Cu(NO3)2.3H2O in the presence of pyz, successive precipitation of known
yellow [(CuII)2(pyz)]n, new orange [CuII(pyz)]n, and new dark blue
{[CuI(pyz)2].I5}n polymeric solids was observed. Starting from the same salt in
the presence of bpy resulted in the successive precipitation of known yellow
[(CuII)2(bpy)]n and new brown {[CuII(NO3)(bpy)2].I3.(dmf.H2O)}n coordination
polymers. By using either Cu(CH3COO)2.H2O or Cu(BF4)2 as starting materials, both
known forms, yellow [(CuII)2(bpy)]n and orange [CuII(bpy)]n, precipitated
successively. The new solids were characterized by IR spectroscopy and X-ray
analysis. [CuII(pyz)]n represents the missing member in the row of two
dimensional coordination networks with general formula [CuIX(pyz)]n (X = Cl, Br,
I). Its steady state and time-resolved characterization together with DFT and
TDDFT calculations revealed that the emission at room temperature is mainly
delayed fluorescence originating from mixed singlet metal-to-ligand charge
transfer and halide-to-ligand charge transfer states, while that at 77 K is
phosphorescence, associated with the small singlet-triplet energy differences
(DeltaE = 70 meV).
PMID- 28418661
TI - Systematic Dissociation Pathway Searches Guided by Principal Component Modes.
AB - We introduce a novel method, Pathway Search guided by Internal Motions (PSIM),
that efficiently finds molecular dissociation pathways of a ligand-receptor
system with guidance from principal component (PC) modes obtained from molecular
dynamics (MD) simulations. Modeling ligand-receptor dissociation pathways can
provide insights into molecular recognition and has practical applications,
including understanding kinetic mechanisms and barriers to binding/unbinding as
well as design of drugs with desired kinetic properties. PSIM uses PC modes in
multilayer internal coordinates to identify natural molecular motions that guide
the search for conformational switches and unbinding pathways. The new multilayer
internal coordinates overcome problems with Cartesian and classical internal
coordinates that fail to smoothly present dihedral rotation or generate
nonphysical distortions. We used HIV-1 protease, which has large-scale flap
motions, as an example protein to demonstrate use of the multilayer internal
coordinates. We provide examples of algorithms and implementation of PSIM with
alanine dipeptide and chemical host-guest systems, 2-naphthyl ethanol-beta
cyclodextrin and tetramethylammonium-cryptophane complexes. Tetramethylammonium
cryptophane has slow binding/unbinding kinetics. Its residence time, the length
to dissociate tetramethylammonium from the host, is ~14 s from experiments, and
PSIM revealed 4 dissociation pathways in approximately 150 CPU h. We also
searched the releasing pathways for the product glyceraldehyde-3-phosphate from
tryptophan synthase, and one complete dissociation pathway was constructed after
running multiple search iterations in approximately 300 CPU h. With guidance by
internal PC modes from MD simulations, the PSIM method has advantages over
simulation-based methods to search for dissociation pathways of molecular systems
with slow noncovalent kinetic behavior.
PMID- 28418663
TI - Airborne Quantification of Methane Emissions over the Four Corners Region.
AB - Methane (CH4) is a potent greenhouse gas and the primary component of natural
gas. The San Juan Basin (SJB) is one of the largest coal-bed methane producing
regions in North America and, including gas production from conventional and
shale sources, contributed ~2% of U.S. natural gas production in 2015. In this
work, we quantify the CH4 flux from the SJB using continuous atmospheric sampling
from aircraft collected during the TOPDOWN2015 field campaign in April 2015.
Using five independent days of measurements and the aircraft-based mass balance
method, we calculate an average CH4 flux of 0.54 +/- 0.20 Tg yr-1 (1sigma), in
close agreement with the previous space-based estimate made for 2003-2009. These
results agree within error with the U.S. EPA gridded inventory for 2012. These
flights combined with the previous satellite study suggest CH4 emissions have not
changed. While there have been significant declines in natural gas production
between measurements, recent increases in oil production in the SJB may explain
why emission of CH4 has not declined. Airborne quantification of outcrops where
seepage occurs are consistent with ground-based studies that indicate these
geological sources are a small fraction of the basin total (0.02-0.12 Tg yr-1)
and cannot explain basinwide consistent emissions from 2003 to 2015.
PMID- 28418664
TI - Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation:
Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5
Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide.
AB - We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5
yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus
hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further
characterization in vivo, compound 1 demonstrated an unacceptable level of brain
penetration. In an effort to reduce the level of brain penetration while
maintaining the overall profile, SAR was developed at the C2' position for a
series of close analogues by employing hydrogen bond donors. As a result, 5-[5
phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was
identified as the lead compound in this series. Compound 25 showed robust effects
in rabbit and canine pharmacodynamic models and an acceptable cross-species
pharmacokinetic profile and was advanced as the clinical candidate. Further
optimization of 25 to mitigate pH-dependent absorption resulted in identification
of the corresponding phosphoramide prodrug (29) with an improved solubility and
pharmacokinetic profile.
PMID- 28418665
TI - Long, Atomically Precise Donor-Acceptor Cove-Edge Nanoribbons as Electron
Acceptors.
AB - This Communication describes a new molecular design for the efficient synthesis
of donor-acceptor, cove-edge graphene nanoribbons and their properties in solar
cells. These nanoribbons are long (~5 nm), atomically precise, and soluble. The
design is based on the fusion of electron deficient perylene diimide oligomers
with an electron rich alkoxy pyrene subunit. This strategy of alternating
electron rich and electron poor units facilitates a visible light fusion reaction
in >95% yield, whereas the cove-edge nature of these nanoribbons results in a
high degree of twisting along the long axis. The rigidity of the backbone yields
a sharp longest wavelength absorption edge. These nanoribbons are exceptional
electron acceptors, and organic photovoltaics fabricated with the ribbons show
efficiencies of ~8% without optimization.
PMID- 28418666
TI - Helical Nanoribbons for Ultra-Narrowband Photodetectors.
AB - This Communication describes a new molecular design that yields ultranarrowband
organic photodetectors. The design is based on a series of helically twisted
molecular ribbons as the optoelectronic material. We fabricate charge collection
narrowing photodetectors based on four different helical ribbons that differ in
the wavelength of their response. The photodetectors made from these materials
have narrow spectral response with full-width at half maxima of <20 nm. The
devices reported here are superior by approximately a factor of 5 to those from
traditional organic materials due to the narrowness of their response. Moreover,
the active layers for the helical ribbon-based photodetectors are solution-cast
but have performance that is comparable to the state-of-the-art narrowband
photodetectors made from methylammonium lead trihalide perovskite single
crystals. The ultranarrow bandwidth for detection results from the helical
ribbons' high absorption coefficient, good electron mobility, and sharp
absorption edges that are defined by the twisted molecular conformation.
PMID- 28418667
TI - Colloid-Facilitated Plutonium Transport in Fractured Tuffaceous Rock.
AB - Colloids have the potential to enhance the mobility of strongly sorbing
radionuclide contaminants in groundwater at underground nuclear test sites. This
study presents an experimental and numerical investigation of colloid-facilitated
plutonium transport in fractured porous media to identify plutonium reactive
transport processes. The transport parameters for dispersion, diffusion,
sorption, and filtration are estimated with inverse modeling by minimizing the
least-squares objective function of multicomponent concentration data from
multiple transport experiments with the shuffled complex evolution metropolis
algorithm. Capitalizing on an unplanned experimental artifact that led to colloid
formation, we adopt a stepwise strategy to first interpret the data from each
experiment separately and then to incorporate multiple experiments simultaneously
to identify a suite of plutonium-colloid transport processes. Nonequilibrium or
kinetic attachment and detachment of plutonium-colloid in fractures were clearly
demonstrated and captured in the inverted modeling parameters along with
estimates of the source plutonium fraction that formed plutonium-colloids. The
results from this study provide valuable insights for understanding the transport
mechanisms and environmental impacts of plutonium in groundwater aquifers.
PMID- 28418668
TI - Computing the Diamagnetic Susceptibility and Diamagnetic Anisotropy of Membrane
Proteins from Structural Subunits.
AB - The behavior of large, complex molecules in the presence of magnetic fields is
experimentally challenging to measure and computationally intensive to predict.
This work proposes a novel, mixed-methods approach for efficiently computing the
principal magnetic susceptibilities and diamagnetic anisotropy of membrane
proteins. The hierarchical primary (amino acid), secondary (alpha helical and
beta sheet), and tertiary (alpha helix and beta barrel) structure of
transmembrane proteins enables analysis of a complex molecule using discrete
subunits of varying size and resolution. The proposed method converts the
magnetic susceptibility tensor for all protein subunits to a unit coordinate
system and sums them to build the magnetic susceptibility tensor for the membrane
protein. Using this approach, we calculate the diamagnetic anisotropy for all
transmembrane proteins of known structure and investigate the effect of different
subunit resolutions on the resulting predictions of diamagnetic anisotropy. We
demonstrate that amino acid residues with aromatic side groups exhibit higher
diamagnetic anisotropies. On average, high percentages of aromatic amino acid
subunits, a beta barrel tertiary structure, and a small volume are correlated
with high volumetric diamagnetic anisotropy. Finally, we demonstrate that
accounting for the spatial position of the residues with respect to one another
is critical to accurately computing the magnetic properties of the complex
protein molecule.
PMID- 28418670
TI - Polarization Effects on the Cellulose Dissolution in Ionic Liquids: Molecular
Dynamics Simulations with Polarization Model and Integrated Tempering Enhanced
Sampling Method.
AB - Conformation of cellulose with various degree of polymerization of n = 1-12 in
ionic liquid 1,3-dimethylimidazolium chloride ([C1mim]Cl) and the intermolecular
interaction between them was studied by means of molecular dynamics (MD)
simulations with fixed-charge and charge variable polarizable force fields,
respectively. The integrated tempering enhanced sampling method was also employed
in the simulations in order to improve the sampling efficiency. Cellulose
undergoes significant conformational changes from a gaseous right-hand helical
twist along the long axis to a flexible conformation in ionic liquid. The
intermolecular interactions between cellulose and ionic liquid were studied by
both infrared spectrum measurements and theoretical simulations. Designated by
their puckering parameters, the pyranose rings of cellulose oligomers are mainly
arranged in a chair conformation. With the increase in the degree of
polymerization of cellulose, the boat and skew-boat conformations of cellulose
appear in the MD simulations, especially in the simulations with polarization
model. The number and population of hydrogen bonds between the cellulose and the
chloride anions show that chloride anion is prone to form HBs whenever it
approaches the hydroxyl groups of cellulose and, thus, each hydroxyl group is
fully hydrogen bonded to the chloride anion. MD simulations with polarization
model presented more abundant conformations than that with nonpolarization model.
The application of the enhanced sampling method further enlarged the
conformational spaces that could be visited by facilitating the system escaping
from the local minima. It was found that the electrostatics interactions between
the cellulose and ionic liquid contribute more to the total interaction energies
than the van der Waals interactions. Although the interaction energy between the
cellulose and anion is about 2.9 times that between the cellulose and cation, the
role of cation is non-negligible. In contrast, the interaction energy between the
cellulose and water is too weak to dissolve cellulose in water.
PMID- 28418671
TI - Area- and Thickness-Dependent Biexciton Auger Recombination in Colloidal CdSe
Nanoplatelets: Breaking the "Universal Volume Scaling Law".
AB - Colloidal nanoplatelets (NPLs) have shown great potentials for lasing
applications due to their sharp absorption and emission peaks, large absorption
cross sections, large radiative decay rates, and long multiexciton lifetimes. How
multiexciton lifetimes depend on material dimensions remains unknown in two
dimensional (2D) materials, despite being a key parameter affecting optical gain
threshold and many other properties. Herein, we report a study of room
temperature biexciton Auger recombination time of CdSe NPLs as a function of
thickness and lateral area. Comparison of all NPLs shows that the biexciton
lifetime does not increase linearly with volume, unlike previously reported
"universal volume scaling law" for quantum dots. For NPLs of the same thickness
(~1.8 nm), the biexciton lifetime increase linearly with their lateral area (from
143.7 +/- 12.6 to 320.1 +/- 17.1 ps when the area increases from 90.5 +/- 21.4 to
234.2 +/- 41.9 nm2). The biexciton lifetime depends linearly on (1/Ek(e))7/2
(Ek(e) is the electron confinement energy) or nearly linearly on d7 (d is NPL
thickness). The observed dependence is consistent with a model in which biexciton
Auger recombination rate scales with the product of exciton binary collision
frequency and Auger recombination probability in biexciton complexes. The linear
increase of Auger lifetimes with NPL lateral areas reflects a 1/area dependence
of the binary collision frequency for 2D excitons and the thickness-dependent
biexciton Auger recombination time is attributed to its strong dependence on the
degree of quantum confinement. This model may be generally applicable to exciton
Auger recombination in quantum confined 1D and 2D nanomaterials.
PMID- 28418673
TI - Aberration-Corrected Electron Beam Lithography at the One Nanometer Length Scale.
AB - Patterning materials efficiently at the smallest length scales is a longstanding
challenge in nanotechnology. Electron-beam lithography (EBL) is the primary
method for patterning arbitrary features, but EBL has not reliably provided sub-4
nm patterns. The few competing techniques that have achieved this resolution are
orders of magnitude slower than EBL. In this work, we employed an aberration
corrected scanning transmission electron microscope for lithography to achieve
unprecedented resolution. Here we show aberration-corrected EBL at the one
nanometer length scale using poly(methyl methacrylate) (PMMA) and have produced
both the smallest isolated feature in any conventional resist (1.7 +/- 0.5 nm)
and the highest density patterns in PMMA (10.7 nm pitch for negative-tone and
17.5 nm pitch for positive-tone PMMA). We also demonstrate pattern transfer from
the resist to semiconductor and metallic materials at the sub-5 nm scale. These
results indicate that polymer-based nanofabrication can achieve feature sizes
comparable to the Kuhn length of PMMA and ten times smaller than its radius of
gyration. Use of aberration-corrected EBL will increase the resolution, speed,
and complexity in nanomaterial fabrication.
PMID- 28418672
TI - A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform
for Triple-Negative Breast Cancer.
AB - Ruthenium coordination complexes have the potential to serve as novel theranostic
agents for cancer. However, a major limitation in their clinical implementation
is effective tumor accumulation. In this study, we have developed a liposome
based theranostic nanodelivery system for [Ru(phen)2dppz](ClO4)2 (Lipo-Ru). This
ruthenium polypyridine complex emits a strong fluorescent signal when
incorporated in the hydrophobic lipid bilayer of the delivery vehicle or in the
DNA helix, enabling visualization of the therapeutic agent in tumor tissues.
Incubation of MDA-MB-231 breast cancer cells with Lipo-Ru induced double-strand
DNA breaks and triggers apoptosis. In a mouse model of triple-negative breast
cancer, treatment with Lipo-Ru dramatically reduced tumor growth. Biodistribution
studies of Lipo-Ru revealed that more than 20% of the injected dose accumulated
in the tumor. These results suggest that Lipo-Ru could serve as a promising
theranostic platform for cancer.
PMID- 28418674
TI - Reversing Enantioselectivity Using Noncovalent Interactions in Asymmetric
Dearomatization of beta-Naphthols: The Power of 3,3' Substituents in Chiral
Phosphoric Acid Catalysts.
AB - The sense of enantioselectivity in asymmetric dearomative amination of beta
naphthols is reported to pivotally depend on the 3,3' substituents on the chiral
BINOL-phosphoric acid (CPA) catalysts. The origin of reversal in the sense of
stereoinduction from R to S, when the aryl substituent is changed from 3,5-(CF3)2
C6H3 (CPA-1) to 9-anthryl (CPA-2), has been identified as arising due to the
change in the pattern of noncovalent interactions (from predominantly C-H...F to
C-H...pi interactions) in the stereocontrolling transition states.
PMID- 28418675
TI - Electric-Field Induced Reversible Switching of the Magnetic Easy Axis in
Co/BiFeO3 on SrTiO3.
AB - Electric-field (E-field) control of magnetism enabled by multiferroic materials
has the potential to revolutionize the landscape of present memory devices
plagued with high energy dissipation. To date, this E-field controlled
multiferroic scheme has only been demonstrated at room temperature using BiFeO3
films grown on DyScO3, a unique and expensive substrate, which gives rise to a
particular ferroelectric domain pattern in BiFeO3. Here, we demonstrate
reversible electric-field-induced switching of the magnetic state of the Co layer
in Co/BiFeO3 (BFO) (001) thin film heterostructures fabricated on (001) SrTiO3
(STO) substrates. The angular dependence of the coercivity and the remanent
magnetization of the Co layer indicates that its easy axis reversibly switches
back and forth 45 degrees between the (100) and the (110) crystallographic
directions of STO as a result of alternating application of positive and negative
voltage pulses between the patterned top Co electrode layer and the (001) SrRuO3
(SRO) layer on which the ferroelectric BFO is epitaxially grown. The coercivity
(HC) of the Co layer exhibits a hysteretic behavior between two states as a
function of voltage. A mechanism based on the intrinsic magnetoelectric coupling
in multiferroic BFO involving projection of antiferromagnetic G-type domains is
used to explain the observation. We have also measured the exact canting angle of
the G-type domain in strained BFO films for the first time using neutron
diffraction. These results suggest a pathway to integrating BFO-based devices on
Si wafers for implementing low power consumption and nonvolatile
magnetoelectronic devices.
PMID- 28418676
TI - Palladium(0)-Catalyzed Dearomative [3 + 2] Cycloaddition of 3-Nitroindoles with
Vinylcyclopropanes: An Entry to Stereodefined 2,3-Fused Cyclopentannulated
Indoline Derivatives.
AB - The palladium(0)-catalyzed diastereoselective dearomative cyclopentannulation of
3-nitroindoles with vinylcyclopropanes is described. This straightforward and
highly atom-economical method leads to a wide range of functionalized indolines
in good yields and diastereoselectivities and represents an unprecedented entry
toward the valuable 2,3-fused cyclopentannulated indoline scaffold.
PMID- 28418677
TI - pH Dependence of Ferricytochrome c Conformational Transitions during Binding to
Cardiolipin Membranes: Evidence for Histidine as the Distal Ligand at Neutral pH.
AB - The conformational changes of ferricytochrome c upon binding to cardiolipin
containing small unilamellar vesicles were studied at slightly acidic pH using
fluorescence, visible circular dichroism, UV-visible absorption, and resonance
Raman spectroscopy. The obtained spectroscopic response data suggest a mode of
interaction, which is clearly distinct from the binding process observed at
neutral pH. Evidence of a reversible and electrostatic binding mechanism under
these conditions is provided through binding inhibition in the presence of 150 mM
NaCl. Moreover, UV-visible absorption and resonance Raman spectra reveal that the
conformational ensemble of membrane bound cytochrome c is dominated by a mixture
of conformers with pentacoordinated and hexacoordinated high-spin heme irons,
which contrast with the dominance of low-spin species at neutral pH. While our
results confirm the L-site binding proposed by Kawai et al., they point to the
protonation of a histidine ligand (H33) as conformational trigger.
PMID- 28418678
TI - Radially Ejected Bubbles Driven by Thermocapillarity in Equilibrated Vapor-Liquid
Mixtures.
AB - We report a novel nucleation method that exploits thermocapillary forces in
binary fluids to generate a cloud of bubbles ejected radially from a thermally
pulsed wire. The bubbles are nucleated within milliseconds of the extinction of
the microsecond pulse and are ejected outward from the wire surface due to the
thermocapillary force created by the radial temperature gradient. At low
temperatures the surface tension of the vapor-liquid mixture, consisting of
ethane-n-octane, increases with increasing temperature, ejecting the bubbles away
from the heated wire. By proper choice of fluid composition, temperature, or
pressure, the sign of the surface tension gradient can be inverted such that
nucleated bubbles are attracted to the wire. As opposed to water-alcohol mixtures
that have a surface tension minimum, we show that this mixture-which we refer to
as an equilibrated vapor-liquid mixture-exhibits a surface tension maximum,
creating a unique set of behaviors which have not yet been fully examined in the
literature.
PMID- 28418679
TI - Bioresponsive Polyoxometalate Cluster for Redox-Activated Photoacoustic Imaging
Guided Photothermal Cancer Therapy.
AB - Although various types of imaging agents have been developed for photoacoustic
(PA) imaging, relatively few imaging agents exhibit high selectivity/sensitivity
to the tumor microenvironment for on-demand PA imaging and therapy. Herein,
molybdenum-based polyoxometalate (POM) clusters with the highest oxidation state
of Mo(VI) (denoted as Ox-POM) were designed as novel agents for redox-activated
PA imaging-guided photothermal therapy. Capable of escaping from recognition and
capture by the liver and spleen, these renal clearable clusters with ultrasmall
size (hydrodynamic size: 1.9 nm) can accumulate in the tumor, self-assemble into
larger nanoclusters at low pH, and are reduced to NIR absorptive agents in the
tumor microenvironment. Studies in 4T1 tumor-bearing mice indicated that these
clusters could be employed for bioresponsive PA imaging-guided tumor ablation in
vivo. Our finding is expected to establish a new physicochemical paradigm for the
design of PA imaging agents based on clusters, bridging the conventional concepts
of "molecule" and "nano" in the bioimaging field.
PMID- 28418680
TI - Dual-Functional Tamm-Dancoff Approximation: A Convenient Density Functional
Method that Correctly Describes S1/S0 Conical Intersections.
AB - Time-dependent Kohn-Sham density functional theory has been used successfully to
compute vertical excitation energies, especially for large molecular systems.
However, the lack of double excitation character in the excited amplitudes
produced by linear response in the adiabatic approximation holds it back from
broader applications in photochemistry; for example, it shows (3N - 7)
dimensional conical intersection seams (where N is the number of atoms) between
ground and excited states, although the correct dimensionality is 3N - 8. In this
letter, we present a new, conceptually simple, easy-to-implement, and easy-to-use
way to employ time-dependent Kohn-Sham density functional theory that has global
accuracy comparable with the conventional single-functional version and that
recovers the double cone topology of the potential energy surfaces at S1/S0
conical intersection seams. The new method is called the dual-functional Tamm
Dancoff approximation (DF-TDA).
PMID- 28418681
TI - Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to
Sofosbuvir, Acelarin, and INX-08189.
AB - A general and efficient method for the synthesis of pronucleotide (ProTide) 5'
phosphoramidate monoesters is reported. This method consists of a highly
stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to
afford the desired target ProTides in excellent yields without employing 3'
protection strategies. The application of this methodology to the synthesis of a
number of pharmaceutically relevant compounds currently marketed or under
investigation in clinical research is demonstrated.
PMID- 28418682
TI - Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase
Behavior and Molecular Assembly Landscapes.
AB - Asphaltenes constitute the heaviest fraction of the aromatic group in crude oil.
Aggregation and precipitation of asphaltenes during petroleum processing costs
the petroleum industry billions of dollars each year due to downtime and
production inefficiencies. Asphaltene aggregation proceeds via a hierarchical
self-assembly process that is well-described by the Yen-Mullins model.
Nevertheless, the microscopic details of the emergent cluster morphologies and
their relative stability under different processing conditions remain poorly
understood. We perform coarse-grained molecular dynamics simulations of a
prototypical asphaltene molecule to establish a phase diagram mapping the self
assembled morphologies as a function of temperature, pressure, and n
heptane:toluene solvent ratio informing how to control asphaltene aggregation by
regulating external processing conditions. We then combine our simulations with
graph matching and nonlinear manifold learning to determine low-dimensional free
energy surfaces governing asphaltene self-assembly. In doing so, we introduce a
variant of diffusion maps designed to handle data sets with large local density
variations, and report the first application of many-body diffusion maps to
molecular self-assembly to recover a pseudo-1D free energy landscape. Increasing
pressure only weakly affects the landscape, serving only to destabilize the
largest aggregates. Increasing temperature and toluene solvent fraction
stabilizes small cluster sizes and loose bonding arrangements. Although the
underlying molecular mechanisms differ, the strikingly similar effect of these
variables on the free energy landscape suggests that toluene acts upon asphaltene
self-assembly as an effective temperature.
PMID- 28418683
TI - Physical Characterization of Tobramycin Inhalation Powder: II. State Diagram of
an Amorphous Engineered Particle Formulation.
AB - Tobramycin Inhalation Powder (TIP) is a spray-dried engineered particle
formulation used in TOBI Podhaler, a drug-device combination for treatment of
cystic fibrosis (CF). A TIP particle consists of two phases: amorphous, glassy
tobramycin sulfate and a gel-phase phospholipid (DSPC). The objective of this
work was to characterize both the amorphous and gel phases following exposure of
TIP to a broad range of RH and temperature. Because, in principle, changes in
either particle morphology or the solid-state form of the drug could affect drug
delivery or biopharmaceutical properties, understanding physical stability was
critical to development and registration of this product. Studies included
morphological assessments of particles, thermal analysis to measure the gel-to
liquid crystalline phase transition (Tm) of the phospholipid and the glass
transition temperature (Tg) of tobramycin sulfate, enthalpy relaxation
measurements to estimate structural relaxation times, and gravimetric vapor
sorption to measure moisture sorption isotherms of TIP and its components.
Collectively, these data enabled development of a state diagram for TIP-a map of
the environmental conditions under which physical stability can be expected. This
diagram shows that, at long-term storage conditions, TIP is at least 50 degrees
C below the Tg of the amorphous phase and at least 40 degrees C below the Tm of
the gel phase. Enthalpy relaxation measurements demonstrate that the
characteristic structural relaxation times under these storage conditions are
many orders of magnitude greater than that at Tg. These data, along with long
term physicochemical stability studies conducted during product development,
demonstrate that TIP is physically stable, remaining as a mechanical solid over
time scales and conditions relevant to a pharmaceutical product. This met a key
design goal in the development of TIP: a room-temperature-stable formulation (3
year shelf life) that obviates the need for refrigeration for long-term storage.
This has enabled development of TOBI Podhaler-an approved inhaled drug product
that meaningfully reduces the treatment burden of CF patients worldwide.
PMID- 28418684
TI - Slow Yogic Breathing and Long-Term Cardiac Autonomic Adaptations: A Pilot Study.
AB - OBJECTIVES: To examine whether long-term practice of yogic breathing alters
cardiac autonomic control. DESIGN: Age-sex matched, cross-sectional, physiologic
pilot study. SETTINGS/LOCATION: Spaulding Rehabilitation Hospital, Cardiovascular
Laboratory, Cambridge, MA. PARTICIPANTS: Twenty-six (26) long-term yoga
practitioners and 26 age- and sex-matched controls, free of cardiovascular
disease. OUTCOME: Cardiac vagal outflow as assessed by respiratory sinus
arrhythmia (RSA). RESULTS: During unpaced (spontaneous) breathing, yoga
practitioners exhibited augmented RSA compared to controls (yoga 364.8 +/- 75.3
vs. 194.7 +/- 46.0 ms2Hz-1, p = 0.03). However, during paced breathing at 0.25 Hz
(15 breaths/min), which accounts for inter- and intravariability in breath rate,
RSA did not differ between groups (yoga 224.8 +/- 48.4 vs. 271.3 +/- 59.7 ms2Hz
1, p = 0.98). Furthermore, the relationship between age and RSA, such that RSA
declines with age, did not qualitatively differ between groups. CONCLUSIONS: Long
term practice of yogic slow breathing does not appear to augment cardiac vagal
control nor prevent known age-related declines.
PMID- 28418685
TI - Does a physical activity program in the nursing home impact on depressive
symptoms? A generalized linear mixed-model approach.
AB - OBJECTIVES: Physical activity (PA) may counteract depressive symptoms in nursing
home (NH) residents considering biological, psychological, and person-environment
transactional pathways. Empirical results, however, have remained inconsistent.
Addressing potential shortcomings of previous research, we examined the effect of
a whole-ecology PA intervention program on NH residents' depressive symptoms
using generalized linear mixed-models (GLMMs). METHOD: We used longitudinal data
from residents of two German NHs who were included without any pre-selection
regarding physical and mental functioning (n = 163, Mage = 83.1, 53-100 years;
72% female) and assessed on four occasions each three months apart. Residents
willing to participate received a 12-week PA training program. Afterwards, the
training was implemented in weekly activity schedules by NH staff. We ran GLMMs
to account for the highly skewed depressive symptoms outcome measure (12-item
Geriatric Depression Scale-Residential) by using gamma distribution. RESULTS:
Exercising (n = 78) and non-exercising residents (n = 85) showed a comparable
level of depressive symptoms at pretest. For exercising residents, depressive
symptoms stabilized between pre-, posttest, and at follow-up, whereas an increase
was observed for non-exercising residents. The intervention group's stabilization
in depressive symptoms was maintained at follow-up, but increased further for non
exercising residents. CONCLUSION: Implementing an innovative PA intervention
appears to be a promising approach to prevent the increase of NH residents'
depressive symptoms. At the data-analytical level, GLMMs seem to be a promising
tool for intervention research at large, because all longitudinally available
data points and non-normality of outcome data can be considered.
PMID- 28418688
TI - Comment on "Checklists for Image-Guided Interventions".
PMID- 28418690
TI - PI-RADS Version 2: Detection of Clinically Significant Cancer in Patients With
Biopsy Gleason Score 6 Prostate Cancer.
AB - OBJECTIVE: The purpose of this study was to analyze the utility of the Prostate
Imaging Reporting and Data System version 2 (PI-RADSv2) in the detection of a
clinically significant cancers in patients with prostate cancers with a biopsy
Gleason score of 6. MATERIALS AND METHODS: A group of 182 consecutively
registered patients with biopsy-proven prostate cancer with a Gleason score of 6
underwent MRI and radical prostatectomy. Clinically significant cancer was
surgically defined as Gleason score of 7 or greater, tumor volume of 0.5 cm3 or
greater, or tumor category T3 or greater. Clinical parameters (prostate-specific
antigen level, greatest percentage of biopsy core, and percentage of positive
cores) and the PI-RADSv2 ratings by three independent readers (experienced
readers 1 and 2, inexperienced reader 3) were investigated. Cutoffs and the
diagnostic performance of PI-RADSv2 for clinically significant cancer were
analyzed. RESULTS: Clinically significant cancer was found in 87.4% (159/182) of
patients. The cutoff PI-RADSv2 score for clinically significant cancer was 4 for
readers 1 and 2 and 5 for reader 3. The AUCs were 0.829 and 0.853 for readers 1
and 2 (p < 0.001) and 0.602 for reader 3 (p = 0.067). For reader 1, sensitivity
was 89.9% (143/159); specificity, 69.6% (16/23); positive predictive value, 95.3%
(143/150); negative predictive value, 50.0% (16/32); and accuracy, 87.4%
(159/182). The corresponding values for reader 2 were 81.1% (129/159), 82.6%
(19/23), 97.0% (129/133), 38.8% (19/49), and 81.3% (148/182). For the experienced
readers, 66.7-81.3% of patients with false-negative results had clinically
significant cancers with tumor volume less than 1 cm3. CONCLUSION: PI-RADSv2 may
help experienced readers identify clinically significant prostate cancers in
patients with a biopsy Gleason score of 6. However, some small (< 1 cm3)
clinically significant cancers can be missed when PI-RADSv2 is used.
PMID- 28418691
TI - Editor's Choice-The organization of chest pain units: Position statement of the
Acute Cardiovascular Care Association.
AB - Chest pain units are defined as organizational short stay units with specific
management protocols designed to facilitate and optimize the diagnosis of
patients presenting with chest pain in the emergency department. The present
document is intended to standardize and facilitate the installation of chest pain
units nearby to the emergency department or as an integral part of the emergency
department. Recommendations on organizational structure, physical and technical
requirements and on disease management are presented. More standardized
installation and implementation of chest pain units will enhance the quality of
chest pain units and improve the quality of care of our chest pain patients.
PMID- 28418692
TI - Drug Repurposing Patent Applications January-March 2017.
PMID- 28418689
TI - An Official American Thoracic Society Workshop Report: Chemical Inhalational
Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical
Preparedness.
AB - This report is based on the proceedings from the Inhalational Lung Injury
Workshop jointly sponsored by the American Thoracic Society (ATS) and the
National Institutes of Health (NIH) Countermeasures Against Chemical Threats
(CounterACT) program on May 21, 2013, in Philadelphia, Pennsylvania. The
CounterACT program facilitates research leading to the development of new and
improved medical countermeasures for chemical threat agents. The workshop was
initiated by the Terrorism and Inhalational Disasters Section of the
Environmental, Occupational, and Population Health Assembly of the ATS.
Participants included both domestic and international experts in the field, as
well as representatives from U.S. governmental funding agencies. The meeting
objectives were to (1) provide a forum to review the evidence supporting current
standard medical therapies, (2) present updates on our understanding of the
epidemiology and underlying pathophysiology of inhalational lung injuries, (3)
discuss innovative investigative approaches to further delineating mechanisms of
lung injury and identifying new specific therapeutic targets, (4) present
promising novel medical countermeasures, (5) facilitate collaborative research
efforts, and (6) identify challenges and future directions in the ongoing
development, manufacture, and distribution of effective and specific medical
countermeasures. Specific inhalational toxins discussed included
irritants/pulmonary toxicants (chlorine gas, bromine, and phosgene), vesicants
(sulfur mustard), chemical asphyxiants (cyanide), particulates (World Trade
Center dust), and respirable nerve agents.
PMID- 28418694
TI - Drug Repurposing Patent Applications October-December 2016.
PMID- 28418693
TI - Validating the Predicted Effect of Astemizole and Ketoconazole Using a Drosophila
Model of Parkinson's Disease.
AB - Parkinson's disease is a growing threat to an ever-ageing population. Despite
progress in our understanding of the molecular and cellular mechanisms underlying
the disease, all therapeutics currently available only act to improve symptoms
and do not stop the disease process. It is therefore imperative that more
effective drug discovery methods and approaches are developed, validated, and
used for the discovery of disease-modifying treatments for Parkinson's. Drug
repurposing has been recognized as being equally as promising as de novo drug
discovery in the field of neurodegeneration and Parkinson's disease specifically.
In this work, we utilize a transgenic Drosophila model of Parkinson's disease,
made by expressing human alpha-synuclein in the Drosophila brain, to validate two
repurposed compounds: astemizole and ketoconazole. Both have been computationally
predicted to have an ameliorative effect on Parkinson's disease, but neither had
been tested using an in vivo model of the disease. After treating the flies in
parallel, results showed that both drugs rescue the motor phenotype that is
developed by the Drosophila model with age, but only ketoconazole treatment
reversed the increased dopaminergic neuron death also observed in these models,
which is a hallmark of Parkinson's disease. In addition to validating the
predicted improvement in Parkinson's disease symptoms for both drugs and
revealing the potential neuroprotective activity of ketoconazole, these results
highlight the value of Drosophila models of Parkinson's disease as key tools in
the context of in vivo drug discovery, drug repurposing, and prioritization of
hits, especially when coupled with computational predictions.
PMID- 28418695
TI - A Comparison of Different Staging Systems for Multiple Myeloma: Can the MRI
Pattern Play a Prognostic Role?
AB - OBJECTIVE: The objective of this study is to compare the most recent systems for
the staging of multiple myeloma (MM), the Durie-Salmon PLUS system and the
International Staging System, according to patients' survival rates and response
to therapy. Another objective is to verify whether patterns of bone marrow
alteration on MRI (i.e., focal, diffuse, or variegated patterns) can provide
prognostic information for patients with MM. MATERIALS AND METHODS: We
retrospectively enrolled 85 patients with MM who were monitored for a minimum of
6 years and who underwent contrast-enhanced spinal and pelvic MRI at 1.5 T and
whole-body FDG PET/CT at the time of diagnosis. Patients underwent MM staging
performed using both staging systems and were divided into groups on the basis of
their MRI patterns. These patient groups were then compared in terms of survival,
response to therapy, and duration of response. RESULTS: Both staging systems
showed great capability in differentiating patients with a worse prognosis from
patients with a better outcome, with the capability of both systems found to be
statistically significant, albeit less statistically significant for the Durie
Salmon PLUS system (p = 0.010 vs p = 0.046, respectively). Patients with a focal
pattern on MRI had a worse survival rate than did the patients with other MRI
patterns (p = 0.032). CONCLUSION: These data indicate that both the International
Staging System and the Durie-Salmon PLUS system have great potential for
characterizing and stratifying MM to determine the survival outcome and therapy
response of patients. Observation of a focal pattern on MRI seems to be
associated with poorer survival.
PMID- 28418696
TI - Eccentric Exercise, Kinesiology Tape, and Balance in Healthy Men.
AB - CONTEXT: Deficits in balance have been identified as a possible risk factor for
knee injuries in athletes. Despite a lack of evidence for its effectiveness,
kinesiology tape (KT) is widely used to prevent knee injuries. OBJECTIVE: To
investigate the influence of KT at the knee joint on balance ability in healthy
men after eccentric exercise. DESIGN: Crossover study. SETTING: University
laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve young men with no history of
lower limb injury volunteered for the study (age = 23.3 +/- 2.6 years). All
participants were students enrolled in a sports science program. INTERVENTION(S):
Participants performed the balance test with and without KT at the knee joint
on 2 separate days. MAIN OUTCOME MEASURE(S): The ability to maintain balance
was assessed during a single-legged-stance test using a computerized balance
stability test system. The test was performed before and after 30 minutes of
downhill walking on a treadmill. RESULTS: Eccentric exercise resulted in a
deterioration of balance ability, which was attenuated by the use of KT. Further
analyses revealed that the effectiveness of KT depended on the participant's
balance status, with the preventive effect being greater in participants
presenting with poorer baseline balance ability. CONCLUSIONS: Applied to the
knee joint, KT counteracted the exercise-related deterioration of balance ability
observed when no tape was used. Participants presenting with below-average
balance ability received more benefit from KT. By preventing exercise-related
impairment of balance ability, KT might help to reduce the risk of sport
associated knee injuries.
PMID- 28418698
TI - Incidence and Risk Factors of Mastitis in Shiraz, Iran: Results of a Cohort
Study.
AB - BACKGROUND: Approximately one in five Western women who breastfeed are likely to
experience acute mastitis. This study investigated the incidence and risk factors
of acute mastitis in a cohort of Iranian women. SUBJECTS AND METHODS: Subjects
were 672 participants of the Shiraz Infant Feeding Study conducted between June
2014 and March 2015. Mothers were recruited from the maternity ward and followed
up at 1, 3, 4, and 6 months postpartum to obtain information on their
breastfeeding practices and experiences. The occurrence of acute mastitis in the
first 26 weeks postpartum was self-reported and the occurrence of acute mastitis
in the first 4 weeks and between 5 and 12 weeks postpartum was treated as
separate outcomes. The risk factors for acute mastitis were explored using
multivariable logistic regression analysis. RESULTS: In total, 130 mothers
(19.3%, 95% confidence interval: 16.3-22.3%) experienced at least one episode of
acute mastitis. Having expressed breast milk and use of a pacifier were
significantly associated with acute mastitis in both the first 4 weeks and
between 5 and 12 weeks postpartum. Persistent problems with cracked or sore
nipples, or engorged breasts, and a reduction in breastfeeding were associated
with acute mastitis between 5 and 12 weeks. CONCLUSIONS: The incidence of acute
mastitis experienced by this cohort of Iranian women is similar to that reported
for women in Western countries. The risk factors of acute mastitis identified in
this study are potentially modifiable and could be prevented or ameliorated with
adequate support and anticipatory guidance provided in the early postpartum
period.
PMID- 28418699
TI - Candida Endocarditis Presenting as Acute Myocardial Infarction.
PMID- 28418700
TI - Three-dimensional analysis of upper airway morphology in skeletal Class III
patients with and without mandibular asymmetry.
AB - OBJECTIVE: To compare the three-dimensional (3D) morphology of the upper airway
in skeletal Class III patients with and without mandibular asymmetry and to
investigate the possible underlying correlations between the morphology of the
upper airway and mandibular deviation. MATERIALS AND METHODS: Cone-beam computed
tomography images of 54 subjects with skeletal Class III malocclusion (ANB angle
<= 0.4 degrees , Wits <= -5.5 degrees ) were taken and 3D upper airway models
were reconstructed using Dolphin 3D software. According to the distance (d) from
symphysis menti to the sagittal plane, all subjects were divided into a symmetry
group (d <= 2 mm) and an asymmetry group (d >= 4 mm). Based on the severity of
mandibular deviation, the asymmetry group was divided into subgroup I (4 mm <=d
<10 mm) and subgroup II (d >= 10 mm). Cross-sectional linear distances, areas,
and volumetric variables of the upper airway were measured in the 3D airway
model. RESULTS: Width of the inferior limit of the glossopharynx (P3W), cross
sectional area of the anterior limit of the nasal airway (P5S), and height of the
glossopharynx (GPH) in the asymmetry group were significantly larger than in the
symmetry group. As for subjects with severe mandibular deviation in subgroup II
(d >= 10 mm), volume of the glossopharynx (GPV), total volume of the pharynx
(TPV), length of the inferior limit of the velopharynx (P2L), and ratio of length
to width of the inferior limit of the velopharynx (P2L/P2W) showed significantly
negative correlations with mandibular deviation (r > 0.7, P < .05). CONCLUSIONS:
In Class III subjects with severe mandibular asymmetry, the pharyngeal airway
showed a tendency toward constriction and presented a more elliptical shape as
mandibular deviation became more severe (P < .01).
PMID- 28418697
TI - A Two-Biomarker Model Predicts Mortality in the Critically Ill with Sepsis.
AB - RATIONALE: Improving the prospective identification of patients with systemic
inflammatory response syndrome (SIRS) and sepsis at low risk for organ
dysfunction and death is a major clinical challenge. OBJECTIVES: To develop and
validate a multibiomarker-based prediction model for 28-day mortality in
critically ill patients with SIRS and sepsis. METHODS: A derivation cohort (n =
888) and internal test cohort (n = 278) were taken from a prospective study of
critically ill intensive care unit (ICU) patients meeting two of four SIRS
criteria at an academic medical center for whom plasma was obtained within 24
hours. The validation cohort (n = 759) was taken from a prospective cohort
enrolled at another academic medical center ICU for whom plasma was obtained
within 48 hours. We measured concentrations of angiopoietin-1, angiopoietin-2, IL
6, IL-8, soluble tumor necrosis factor receptor-1, soluble vascular cell adhesion
molecule-1, granulocyte colony-stimulating factor, and soluble Fas. MEASUREMENTS
AND MAIN RESULTS: We identified a two-biomarker model in the derivation cohort
that predicted mortality (area under the receiver operator characteristic curve
[AUC], 0.79; 95% confidence interval [CI], 0.74-0.83). It performed well in the
internal test cohort (AUC, 0.75; 95% CI, 0.65-0.85) and the external validation
cohort (AUC, 0.77; 95% CI, 0.72-0.83). We determined a model score threshold
demonstrating high negative predictive value (0.95) for death. In addition to a
low risk of death, patients below this threshold had shorter ICU length of stay,
lower incidence of acute kidney injury, acute respiratory distress syndrome, and
need for vasopressors. CONCLUSIONS: We have developed a simple, robust biomarker
based model that identifies patients with SIRS/sepsis at low risk for death and
organ dysfunction.
PMID- 28418701
TI - Cementogenesis is inhibited under a mechanical static compressive force via
Piezo1.
AB - OBJECTIVE: To investigate whether Piezo1, a mechanotransduction gene mediates the
cementogenic activity of cementoblasts under a static mechanical compressive
force. MATERIALS AND METHODS: Murine cementoblasts (OCCM-30) were exposed to a
2.0 g/cm2 static compressive force for 3, 6, 12, and 24 hours. Then the
expression profile of Piezo1 and the cementogenic activity markers
osteoprotegerin (Opg), osteopontin (Opn), osteocalcin (Oc), and protein tyrosine
phosphataselike member A (Ptpla) were analyzed. Opg, Opn, Oc, and Ptpla
expression was further measured after using siRNA to knock down Piezo1. Real-time
PCR, Western blot, and cell proliferation assays were performed according to
standard procedures. RESULTS: After mechanical stimulation, cell morphology and
proliferation did not change significantly. The expression of Piezo1, Opg, Opn,
Oc, and Ptpla was significantly decreased, with a high positive correlation
between Opg and Piezo1 expression. After Piezo1 knockdown, the expression of Opg,
Opn, Oc, and Ptpla was further decreased under mechanical stimulation.
CONCLUSIONS: Cementogenic activity was inhibited in OCCM-30 cells under static
mechanical force, a process that was partially mediated by the decrease of
Piezo1. This study provides a new viewpoint of the pathogenesis mechanism of
orthodontically induced root resorption and repair.
PMID- 28418702
TI - Pancreatic Calcifications and Calcified Pancreatic Masses: Pattern Recognition
Approach on CT.
AB - OBJECTIVE: The purpose of this article is to review a spectrum of calcified
pancreatic masses and propose an algorithm for diagnostic radiologic evaluation.
CONCLUSION: Pancreatic calcifications are being detected more frequently because
of the widespread use of imaging, particularly CT. Pancreatic calcifications are
most commonly associated with chronic pancreatitis related to alcohol abuse.
Several other pathologic entities, however, can cause pancreatic calcifications.
Familiarity with these entities and their CT appearance is helpful in making an
accurate diagnosis.
PMID- 28418703
TI - Radioresistance of Adenine to Cosmic Rays.
AB - The presence of nucleobases in carbonaceous meteorites on Earth is an indication
of the existence of this class of molecules in outer space. However, space is
permeated by ionizing radiation, which can have damaging effects on these
molecules. Adenine is a purine nucleobase that amalgamates important biomolecules
such as DNA, RNA, and ATP. Adenine has a unique importance in biochemistry and
therefore life. The aim of this work was to study the effects of cosmic ray
analogues on solid adenine and estimate its survival when exposed to corpuscular
radiation. Adenine films were irradiated at GANIL (Caen, France) and GSI
(Darmstadt, Germany) by 820 MeV Kr33+, 190 MeV Ca10+, 92 MeV Xe23+, and 12 MeV
C4+ ion beams at low temperature. The evolution of adenine molecules under heavy
ion irradiation was studied by IR absorption spectroscopy as a function of
projectile fluence. It was found that the adenine destruction cross section
(sigmad) follows an electronic stopping power (Se) power law under the form:
CSen; C is a constant, and the exponential n is a dimensionless quantity. Using
the equation above to fit our results, we determined sigmad = 4 * 10-17 Se1.17,
with Se in kiloelectronvolts per micrometer (keV MUm-1). New IR absorption bands
arise under irradiation of adenine and can be attributed to HCN, CN-, C2H4N4,
CH3CN, and (CH3)3CNC. These findings may help to understand the stability and
chemistry related to complex organic molecules in space. The half-life of solid
adenine exposed to the simulated interstellar medium cosmic ray flux was
estimated as (10 +/- 8) * 106 years. Key Words: Heavy ions-Infrared spectroscopy
Astrochemistry-Cosmic rays-Nucleobases-Adenine. Astrobiology 17, 298-308.
PMID- 28418705
TI - Accurate Differentiation of Carotenoid Pigments Using Flight Representative Raman
Spectrometers.
AB - Raman spectrometers will be utilized on two Mars rover missions, ExoMars and Mars
2020, in the near future, to search for evidence of life and habitable geological
niches on Mars. Carotenoid pigments are recognized target biomarkers, and as they
are highly active in Raman spectroscopy, they can be readily used to characterize
the capabilities of space representative instrumentation. As part of the
preparatory work being performed for the ExoMars mission, a gypsum crust
colonized by microorganisms was interrogated with commercial portable Raman
instruments and a flight representative Raman laser spectrometer. Four separate
layers, each exhibiting different coloration resulting from specific halophilic
microorganism activities within the gypsum crust, were studied by using two
excitation wavelengths: 532 and 785 nm. Raman or fluorescence data were readily
obtained during the present study. Gypsum, the main constituent of the crust, was
detected with both excitation wavelengths, while the resonance Raman signal
associated with carotenoid pigments was only detected with a 532 nm excitation
wavelength. The fluorescence originating from bacteriochlorophyll a was found to
overwhelm the Raman signal for the layer colonized by sulfur bacteria when
interrogated with a 785 nm excitation wavelength. Finally, it was demonstrated
that portable instruments and the prototype were capable of detecting a
statistically significant difference in band positions of carotenoid signals
between the sample layers. Key Words: Gypsum-Raman spectrometers-Carotenoids
ExoMars-Mars exploration-Band position shift. Astrobiology 17, 351-362.
PMID- 28418704
TI - False Negatives for Remote Life Detection on Ocean-Bearing Planets: Lessons from
the Early Earth.
AB - Ocean-atmosphere chemistry on Earth has undergone dramatic evolutionary changes
throughout its long history, with potentially significant ramifications for the
emergence and long-term stability of atmospheric biosignatures. Though a great
deal of work has centered on refining our understanding of false positives for
remote life detection, much less attention has been paid to the possibility of
false negatives, that is, cryptic biospheres that are widespread and active on a
planet's surface but are ultimately undetectable or difficult to detect in the
composition of a planet's atmosphere. Here, we summarize recent developments from
geochemical proxy records and Earth system models that provide insight into the
long-term evolution of the most readily detectable potential biosignature gases
on Earth-oxygen (O2), ozone (O3), and methane (CH4). We suggest that the
canonical O2-CH4 disequilibrium biosignature would perhaps have been challenging
to detect remotely during Earth's ~4.5-billion-year history and that in general
atmospheric O2/O3 levels have been a poor proxy for the presence of Earth's
biosphere for all but the last ~500 million years. We further suggest that
detecting atmospheric CH4 would have been problematic for most of the last ~2.5
billion years of Earth's history. More broadly, we stress that internal oceanic
recycling of biosignature gases will often render surface biospheres on ocean
bearing silicate worlds cryptic, with the implication that the planets most
conducive to the development and maintenance of a pervasive biosphere will often
be challenging to characterize via conventional atmospheric biosignatures. Key
Words: Biosignatures-Oxygen-Methane-Ozone-Exoplanets-Planetary habitability.
Astrobiology 17, 287-297.
PMID- 28418706
TI - Radiation-Driven Formation of Reactive Oxygen Species in Oxychlorine-Containing
Mars Surface Analogues.
AB - The present study demonstrates that gamma-radiolyzed perchlorate-containing Mars
soil salt analogues (in a CO2 atmosphere) generate upon H2O wetting the reactive
oxygen species (ROS) superoxide radical (O2*-), hydrogen peroxide (H2O2), and
hydroxyl radicals (*OH). This study also validates that analogue radiolysis forms
oxychlorine species that, in turn, can UV-photolyze to *OH upon UV photolysis.
This investigation was made possible by the development of a new assay for
inorganic-origin O2*- and H2O2 determination and by the modification of a
previous assay for soil *OH. Results show that radiolyzed Mg(ClO4)2 generates
H2O2 and *OH; and when included as part of a mixture analogous to the salt
composition of samples analyzed at the Mars Phoenix site, the analogue generated
O2*-, H2O2, and *OH, with *OH levels 150-fold higher than in the radiolyzed
Mg(ClO4)2 samples. Radiolyzed Mars Phoenix site salt analogue that did not
contain Mg(ClO4)2 generated only *OH also at 150-fold higher concentration than
Mg(ClO4)2 alone. Additionally, UV photolysis of the perchlorate gamma radiolysis
product chlorite (ClO2-) generated the oxychlorine products trihalide (Cl3-),
chlorine dioxide (ClO2*), and hypochlorite (ClO-), with the formation of *OH by
UV photolysis of ClO-. While the generation of ROS may have contributed in part
to 14CO2 production in the Viking Labeled Release (LR) experiment and O2 (g)
release in the Viking Gas Exchange (GEx) experiment, our results indicate that
they are not likely to be the major contributor to the LR and GEx results.
However, due to their highly reactive nature, they are expected to play a
significant role in the alteration of organics on Mars. Additionally, experiments
with hypochlorite show that the thermal stability of NaClO is in the range of the
thermal stability observed for thermally liable oxidant responsible for the
Viking LR results. Key Words: Mars-Oxygen-Salts-Radiation-Habitability.
Astrobiology 17, 319-336.
PMID- 28418708
TI - Long Trekking Experience at High Altitude Causes Testicular Volumetric Reduction
in Humans: Evidence Based on Magnetic Resonance Imaging.
PMID- 28418707
TI - Liquid Water Restricts Habitability in Extreme Deserts.
AB - Liquid water is a requirement for biochemistry, yet under some circumstances it
is deleterious to life. Here, we show that liquid water reduces the upper
temperature survival limit for two extremophilic photosynthetic microorganisms
(Gloeocapsa and Chroococcidiopsis spp.) by greater than 40 degrees C under
hydrated conditions compared to desiccated conditions. Under hydrated conditions,
thermal stress causes protein inactivation as shown by the fluorescein diacetate
assay. The presence of water was also found to enhance the deleterious effects of
freeze-thaw in Chroococcidiopsis sp. In the presence of water, short-wavelength
UV radiation more effectively kills Gloeocapsa sp. colonies, which we hypothesize
is caused by factors including the greater penetration of UV radiation into
hydrated colonies compared to desiccated colonies. The data predict that deserts
where maximum thermal stress or irradiation occurs in conjunction with the
presence of liquid water may be less habitable to some organisms than more
extreme arid deserts where organisms can dehydrate prior to being exposed to
these extremes, thus minimizing thermal and radiation damage. Life in extreme
deserts is poised between the deleterious effects of the presence and the lack of
liquid water. Key Words: Deserts-Extremophiles-Stress-High temperatures-UV
radiation-Desiccation. Astrobiology 17, 309-318.
PMID- 28418709
TI - Psychological Assessment With the MMPI-2/MMPI-2-RF, 3rd ed., by A. F. Friedman,
P. K. Bolinskey, R. W. Levak, & D. S. Nichols.
PMID- 28418710
TI - Lung cancer guidelines in Sweden, Denmark, Norway and Finland: a comparison.
AB - BACKGROUND: The Nordic countries are similar in terms of demographics and health
care organization. Yet there are marked differences in lung cancer mortality, for
which Denmark historically has had the poorest outcome. One of several possible
reasons for these differences could have to do with how lung cancer is diagnosed
and treated in the different Nordic countries. However, among the four most
populous Nordic countries: Sweden, Denmark, Norway and Finland, there is a
paucity of knowledge about differences and similarities in recommendations in the
national guidelines for non-small cell lung cancer (NSCLC) and the methodology by
which the guidelines are developed. METHODS: We identified and evaluated the
development and content of the available clinical care guidelines for NSCLC in
the four countries. Moreover, we compared the integrated cancer pathways in these
countries. We have used case examples to illustrate areas with clear differences
in clinical care recommendations. RESULTS: There are notable differences in the
methodology by which the guidelines are developed, published and updated to
comply with international recommendations. The Norwegian guidelines are developed
and updated according to the most rigorous methodology and have so far been
updated most frequently. We found that on the basis of recommendations patients
with NSCLC are treated differently with regard to bevacizumab therapy and
radiation dosing regimens. Cerebral imaging practices in patients with locally
advanced NSCLC also differ. There is, moreover, a marked difference with regard
to efforts to help patients to quit smoking. All except Finland have integrated
cancer pathways for fast track diagnosis and treatment. Guidelines for follow-up
of lung cancer patients also differ, with the Danish follow-up regimen as the
most comprehensive. To obtain consensus on optimal clinical care, areas with
differences in recommendations or where recommendations are based on a low level
of evidence should be subjected to further studies.
PMID- 28418711
TI - Silibinin Improves TNF-alpha and M30 Expression and Histological Parameters in
Rat Kidneys After Hepatic Ischemia/Reperfusion.
AB - BACKGROUND: Remote kidney damage is a sequel of hepatic ischemia-reperfusion
(I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed
extract with known antioxidant and hepatoprotective activity. Our study
investigates the nephroprotective potential of intravenously administered
silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in
hepatic I/R injury. MATERIAL AND METHODS: 63 Wistar rats were divided into three
groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion);
and Silibinin (200 MUL intravenous silibinin administration after 45 min of
ischemia). Kidney tissues were collected to determine TNF-alpha, M30 and
histopathological changes at predetermined time intervals. RESULTS: Comparing
Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-alpha
and M30 expression. Deterioration was observed in hyperemia/filtration of renal
parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue
swelling index). Intravenous silibinin administration and comparison of the
Control vs. Silibinin groups showed a statistically significant decrease in TNF
alpha levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p =
0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in:
hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p =
0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120
min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical
filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and
edema (240 min - p = 0.001). CONCLUSION: Our study confirms that hepatic I/R
injury causes remote renal damage while the intravenous administration of
silibinin leads to statistically significant nephroprotective action.
PMID- 28418712
TI - A Cross-Sectional Study of Indoor Tanning in Fitness Centres.
AB - BACKGROUND: Ultraviolet (UV) radiation is a human carcinogen and is associated
with the development of skin cancer. The promotion of indoor tanning (IT) at
fitness centres is of particular concern as it reinforces the idea that a tan is
associated with health and fitness. The purpose of this study was to investigate
the prevalence of IT in fitness centres, with an emphasis on determining the
financial costs, adherence to regulations, and safety precautions. METHODS: Ten
cities, representing 9 different Canadian provinces, were chosen for the study.
From each province, a minimum of 20 and a maximum of 30 fitness centres were
randomly selected from the Yellow Pages website. Each fitness centre was
contacted by the principal investigator and inquiries were made from a consumer's
perspective. RESULTS: Of the 203 gyms surveyed, 43% (88/203) offered tanning
facilities. Of these, 10.23% (9/88) were found to be noncompliant with the
provincial IT regulations for age and/or time between tanning sessions.
INTERPRETATION: Despite the known risks of IT, not all fitness centres are
compliant with provincial legislations regarding IT, and some continue to promote
tanning access to minors.
PMID- 28418713
TI - Defence factors of vaginal lactobacilli.
AB - Accurate knowledge of the composition and ecology of the vaginal microbial
environment in healthy women is necessary for understanding lactobacilli
dominated normal microbiota and the mechanisms by which it reduces disease risk.
The vagina and its microbiota form a balanced ecosystem; any movement outside the
normal range for this ecosystem of obligate and/or facultative microbes, termed
dysbacteriosis, can lead to infection and disease. This review summarizes recent
research on the vaginal ecosystem, the Lactobacillus species that dominate it,
and the means by which they suppress the growth, development, and/or
proliferation of pathogenic microbial species. Lactobacilli colonization is
believed to be beneficial since it prevents other microorganisms from colonizing
the vaginal epithelium via competitive adhesion, interactions with the local
immunity and plasminogen-plasmin system, and the production of lactic acid,
hydrogen peroxide, and antibacterial substances. In addition, lactobacilli also
constitute an important part of the urogenital tract microbiota and the
lactobacilli-dominated vaginal microbiome is a major determinant for female
urogenital health.
PMID- 28418714
TI - More Than a Physical Burden: Women's Mental and Emotional Work in Preventing
Pregnancy.
AB - In the United States, responsibility for preventing pregnancy in heterosexual
relationships disproportionately falls on women. While the biotechnological
landscape of available methods may explain the assignment of the physical burden
for contraception to women, this does not mean the concomitant time, attention,
and stress that preventing pregnancy requires must also be primarily assumed by
women. Building on work identifying health care providers as contributors to the
construction of normative ideas about reproduction, this study analyzed 52
contraceptive counseling visits with women who reported they did not want future
children for the construction of responsibility for the mental and emotional
aspects of contraception. Offering a case of how gender inequality is
(re)produced through clinical encounters, findings demonstrate that clinicians
discursively constructed these responsibilities as women's and point to
structural aspects of the visit itself that reify this unequal burden as normal.
Results are consistent with research identifying the broader feminization of
family health work in heterosexual relationships. To the extent that the
distribution of the mental and emotional responsibilities of preventing pregnancy
is both a product of and contributor to gender inequality, this analysis yields
insight into the production-and possible deconstruction-of (reproductive) health
care as a gendered social structure.
PMID- 28418715
TI - Evaluation of Selective-Enrichment and Chromogenic Media for Salmonella Detection
in Raw Shell Egg Contents with a Low Microbial Load.
AB - The current study was conducted to evaluate the ability to recover Salmonella
from shell egg contents by culture methods. A total of 4,000 eggs were obtained
from a grading and packing center located in the Gyeonggi Province of South
Korea, and 200 samples were created by pooling 20 broken eggs. The pooled samples
were held at room temperature for 4 d before a 25-mL aliquot of each pool was
added to 225 mL of modified trypticase soy broth (mTSB) and incubated at 35
degrees C for 24 +/- 2 h. A loopful of the culture was streaked onto chromogenic
Druggan-Forsythe-Iversen (DFI) agar and incubated at 36 +/- 1 degrees C for 18-24
h. In addition, 1 mL and/or 0.1 mL of the mTSB cultures were added to 10 mL of
Muller-Kauffmann tetrathionate with novobiocin (MKTTn) or Rappaport-Vassiliadis
(RV) broth, and they were incubated for 24 +/- 2 h at 35 +/- 2 degrees C or 42 +/
0.2 degrees C, respectively. A loopful from these cultures was streaked onto
Brilliant Green (BG), xylose lysine deoxycholate (XLD), and bismuth sulfite (BS)
agar plates, respectively. Directly streaking onto DFI agar revealed the presence
of Salmonella in 14 out of the 200 pooled samples (7%); whereas the combination
of RV medium and BG, XLD, and BS agar detected the pathogen in only 9 (4.5%), 7
(3.5%), and 3 (1.5%) of the pooled samples, respectively. When MKTTn broth was
used, Salmonella was detected in 7 (3.5%), 2 (1%), and 0 (0%) of the samples when
streaked onto BG, XLD, and BS agar, respectively. The results indicate that
direct plating onto DFI agar without enrichment was the most suitable among the
methods evaluated in this study for detecting Salmonella in raw shell egg
contents with a low microbial load.
PMID- 28418716
TI - Development and Initial Validation of the Five-Factor Model Adolescent
Personality Questionnaire (FFM-APQ).
AB - This research reports on the 4-phase development of the 25-item Five-Factor Model
Adolescent Personality Questionnaire (FFM-APQ). The purpose was to develop and
determine initial evidence for validity of a brief adolescent personality
inventory using a vocabulary that could be understood by adolescents up to 18
years old. Phase 1 (N = 48) consisted of item generation and expert (N = 5)
review of items; Phase 2 (N = 179) involved item analyses; in Phase 3 (N = 496)
exploratory factor analysis assessed the underlying structure; in Phase 4 (N =
405) confirmatory factor analyses resulted in a 25-item inventory with 5
subscales.
PMID- 28418717
TI - Diversity of Endophytic Bacteria in a Fern Species Dryopteris uniformis (Makino)
Makino and Evaluation of Their Antibacterial Potential Against Five Foodborne
Pathogenic Bacteria.
AB - The fern plant Dryopteris uniformis has traditionally been used in herbal
medicine and possesses many biological activities. This study was conducted to
explore the endophytic bacterial diversity associated with D. uniformis and
evaluate their antibacterial potential against foodborne pathogenic bacteria
(FPB). Among 51 isolated endophytic bacteria (EB), 26 EB were selected based on
their morphological characteristics and identified by 16S rRNA gene analysis. The
distribution of EB was diverse in the leaf and the stem/root tissues. When the EB
were screened for antibacterial activity against five FPB, Listeria
monocytogenes, Salmonella Typhimurium, Bacillus cereus, Staphylococcus aureus,
and Escherichia coli O157:H7, four EB Bacillus sp. cryopeg, Paenibacillus sp.
rif200865, Staphylococcus warneri, and Bacillus psychrodurans had a broad
spectrum of antibacterial activity (9.58 +/- 0.66 to 21.47 +/- 0.27 mm inhibition
zone). The butanol solvent extract of B. sp. cryopeg and P. sp. rif200865
displayed effective antibacterial activity against the five FPB, which was
evident from the scanning electron microscopy with irregular or burst cell
morphology in the EB-treated bacteria compared to smooth and regular cells in
case of the control bacteria. The minimum inhibitory concentration and minimum
bactericidal concentration values ranged between 250-500 MUg/mL and 500-100
MUg/mL, respectively. The above outcomes signify the huge prospective of the
selected EB in the food industry. Overall, the above results suggested that D.
uniformis contains several culturable EB that possess effective antibacterial
compounds, and that EB can be utilized as a source of natural antibacterial
agents for their practical application in food industry to control the spread of
FPB as a natural antibacterial agent.
PMID- 28418718
TI - Socially Interactive and Passive Technologies Enhance Friendship Quality: An
Investigation of the Mediating Roles of Online and Offline Self-Disclosure.
AB - Previous studies indicate that characteristics of social-based technologies (STs)
stimulate the sharing of intimate information online, which in turn enhances the
quality of friendships. In addition, intimate online self-disclosure has been
positively associated with offline self-disclosure. One objective of the current
study was to combine the literature and test a model which postulates that STs
use stimulates online self-disclosure which facilitates offline self-disclosure
and, thereby, enhances the quality of close friendships. A second objective of
this study was to examine if the aforementioned model applies to two categories
of STs, including socially interactive technologies (SITs; e.g., instant
messaging) and socially passive technologies (SPTs; e.g., reading posts on social
networking sites). An online survey was conducted with 212 young adults between
18 and 25 years of age. The proposed indirect positive effects of SITs and SPTs
use on the quality of friendships were supported. The positive effect of SITs use
on the quality of friendships was explained entirely by the young adults'
disclosure of personal information when using SITs which facilitated intimate
self-disclosure during face-to-face interactions. Although there was not a direct
effect of SPTs use on the quality of friendships, SPTs use was positively related
to SPTs self-disclosure, which had a positive effect on offline self-disclosure.
The current study enhances our understanding regarding the positive effects
associated with the use of STs among close friends and identifies the
contribution of online self-disclosure for offline interactions.
PMID- 28418719
TI - The Incremental Validity of Self-Report and Performance-Based Methods for
Assessing Hostility to Predict Cardiovascular Disease in Physicians.
AB - We evaluated the utility of an integrative, multimethod approach for assessing
hostility-related constructs to predict premature cardiovascular disease (CVD)
and premature coronary heart disease (CHD) using participants from the Johns
Hopkins Precursors Study, which was designed to identify risk factors for heart
disease. Participants were assessed at baseline while in medical school from 1946
to 1962 (M age = 24.6) and have been followed annually since then. Baseline
assessment included individually administered Rorschach protocols (N = 416)
scored for aggressive imagery (i.e., Aggressive Content, Aggressive Past) and
self-reports of 3 possible anger responses to stress. Cox regression analyses
predicting morbidity or mortality by age 55 revealed a significant interaction
effect; high levels of Aggressive Content with high self-reported hostility
predicted an increased rate of premature CVD and CHD, and incrementally predicted
the rate of these events after controlling for the significant covariates of
smoking (CVD and CHD) and cholesterol (CHD) that were also assessed at baseline.
The hostility and anger measures, as well as other baseline covariates, were not
predictors of CVD risk factors assessed at midlife during follow-up. Overall,
this integrative model of hostility illustrates the potential value of
multimethod assessment to areas of health psychology and preventive medicine.
PMID- 28418720
TI - Effectiveness and outcomes of thermablate endometrial ablation system in women
with heavy menstrual bleeding.
AB - Heavy menstrual bleeding (HMB) is a common problem in women of reproductive age
group with major impact on their quality of life (QoL). The aim was to study the
short-term effectiveness of Thermablate Endometrial Ablation System (EAS) and its
impact on QoL in women with HMB. This was a prospective cohort study conducted on
consecutive 72 women suffering from HMB. The success rate was estimated and
patients' QoL was compared before and after the procedure using the Aberdeen
menorrhagia severity scale. The mean follow-up period was 18 months (6-24
months). The mean age and body mass index were 48 (+/-5.2) years 33.2 (+/-7.4)
kg/m2 respectively. Among treated participants, 58 (80.6%) reported the absence
of bleeding. A significant decrease was observed in the rate of missed social
activity and increase in the leisure time activities. The overall patient
satisfaction was 95.7%. Thermablate EAS is an effective minimally invasive
treatment with marked improvement in QoL in women with HMB. Impact statement
Heavy menstrual bleeding (HMB) is a common problem that affects 11-13% of
reproductive age women with major impact on their quality of life (QoL). A
variety of methods for endometrial ablation has been used for the destruction of
the endometrial lining to treat HMB. The short-term results of this study shows
amenorrhoea rate of (80.6%) after the procedure and a significant decrease in the
rate of missed social activity and increase in the leisure time activities with
marked improvement in QoL. The overall patient satisfaction was 95.7%.
Thermablate Endometrial Ablation System is an effective minimally invasive
treatment for HMB with advantages of shorter operating time, shorter hospital
stay and high-level patient satisfaction. However, further clinical research with
large-scale studies and possible comparison with other treatment options are
recommended.
PMID- 28418722
TI - Correction to: Patient Personality and Relational Patterns in Psychotherapy:
Factor Structure, Reliability, and Validity of the Psychotherapy Relationship
Questionnaire.
PMID- 28418721
TI - Practical Applications of Generalizability Theory for Designing, Evaluating, and
Improving Psychological Assessments.
AB - In this article, we illustrate how generalizability theory (G-theory) can extend
traditional assessment methods for designing, improving, and evaluating results
from both objectively and subjectively scored measures of individual differences.
Our illustrations include quantification of multiple sources of measurement
error, derivation of unique indexes of consistency for norm- and criterion
referenced interpretations of scores, estimation of score consistency when
changing a measurement procedure, and disattenuation of correlation coefficients
for measurement error. We also expand G-theory analyses beyond the item level to
include parcels and split measures and highlight linkages among G-theory,
classical test theory, and structural equation modeling. Computer code and sample
data are provided in online supplements to help readers apply the demonstrated
techniques to their own assessments.
PMID- 28418723
TI - Ethnomedical and Sociocultural Factors of Pica Substances in Rural South India.
AB - Pica, the intentional ingestion of culturally determined "nonfood" substances,
occurs cross-culturally and most commonly during pregnancy. The current study
describes women's perceptions of ethnomedical and sociocultural aspects of pica
along with familial acquisition and transmission of knowledge and behaviors in a
South Indian population. Findings showed that in contrast to Western models of
pica, nonfood consumption is not entirely taboo; consumers rely on local remedies
to cure overconsumption; and perceptions of prevalence extend beyond pregnancy.
Future research on pica should consider consumption patterns outside of pregnancy
and the role stigma plays in individuals seeking assistance for overconsumption.
PMID- 28418724
TI - Long Noncoding RNA MEG3 Negatively Regulates Proliferation and Angiogenesis in
Vascular Endothelial Cells.
AB - Long noncoding RNA (lncRNA) MEG3 is an important tumor suppressor in several
types of human cancers. However, the biological function and underlying mechanism
of MEG3 in vascular endothelial cells (VECs) remain unknown. In the present
study, we demonstrated the functional importance of lncRNA MEG3 in proliferation
and angiogenesis of VECs. MEG3 overexpression significantly suppressed the
proliferation and in vitro angiogenesis in VECs, whereas knockdown of MEG3 had
the opposite effect. Furthermore, we found that MEG3 exerts its function through
negatively regulating miR-9 by acting as a microRNA sponge. Taken together, MEG3
miR-9 plays an important role in proliferation and angiogenesis in VECs.
PMID- 28418725
TI - MEDEX 2015: Heart Rate Variability Predicts Development of Acute Mountain
Sickness.
AB - : Sutherland, Angus, Joseph Freer, Laura Evans, Alberto Dolci, Matteo Crotti, and
Jamie Hugo Macdonald. MEDEX 2015: Heart rate variability predicts development of
acute mountain sickness. High Alt Med Biol. 18: 199-208, 2017. AIMS: Acute
mountain sickness (AMS) develops when the body fails to acclimatize to
atmospheric changes at altitude. Preascent prediction of susceptibility to AMS
would be a useful tool to prevent subsequent harm. Changes to peripheral oxygen
saturation (SpO2) on hypoxic exposure have previously been shown to be of poor
predictive value. Heart rate variability (HRV) has shown promise in the early
prediction of AMS, but its use pre-expedition has not previously been
investigated. We aimed to determine whether pre- and intraexpedition HRV
assessment could predict susceptibility to AMS at high altitude with better
diagnostic accuracy than SpO2. METHODS: Forty-four healthy volunteers undertook
an expedition in the Nepali Himalaya to >5000 m. SpO2 and HRV parameters were
recorded at rest in normoxia and in a normobaric hypoxic chamber before the
expedition. On the expedition HRV parameters and SpO2 were collected again at
3841 m. A daily Lake Louise Score was obtained to assess AMS symptomology.
RESULTS: Low frequency/high frequency (LF/HF) ratio in normoxia (cutpoint <=2.28
a.u.) and LF following 15 minutes of exposure to normobaric hypoxia had moderate
(area under the curve >=0.8) diagnostic accuracy. LF/HF ratio in normoxia had the
highest sensitivity (85%) and specificity (88%) for predicting AMS on subsequent
ascent to altitude. In contrast, pre-expedition SpO2 measurements had poor (area
under the curve <0.7) diagnostic accuracy and inferior sensitivity and
specificity. CONCLUSIONS: Pre-ascent measurement of HRV in normoxia was found to
be of better diagnostic accuracy for AMS prediction than all measures of HRV in
hypoxia, and better than peripheral oxygen saturation monitoring.
PMID- 28418726
TI - U50: A New Metric for Measuring Assembly Output Based on Non-Overlapping, Target
Specific Contigs.
AB - Advances in next-generation sequencing technologies enable routine genome
sequencing, generating millions of short reads. A crucial step for full genome
analysis is the de novo assembly, and currently, performance of different
assembly methods is measured by a metric called N50. However, the N50 value can
produce skewed, inaccurate results when complex data are analyzed, especially for
viral and microbial datasets. To provide a better assessment of assembly output,
we developed a new metric called U50. The U50 identifies unique, target-specific
contigs by using a reference genome as baseline, aiming at circumventing some
limitations that are inherent to the N50 metric. Specifically, the U50 program
removes overlapping sequence of multiple contigs by utilizing a mask array, so
the performance of the assembly is only measured by unique contigs. We compared
simulated and real datasets by using U50 and N50, and our results demonstrated
that U50 has the following advantages over N50: (1) reducing erroneously large
N50 values due to a poor assembly, (2) eliminating overinflated N50 values caused
by large measurements from overlapping contigs, (3) eliminating diminished N50
values caused by an abundance of small contigs, and (4) allowing comparisons
across different platforms or samples based on the new percentage-based metric
UG50%. The use of the U50 metric allows for a more accurate measure of assembly
performance by analyzing only the unique, non-overlapping contigs. In addition,
most viral and microbial sequencing have high background noise (i.e., host and
other non-targets), which contributes to having a skewed, misrepresented N50
value-this is corrected by U50. Also, the UG50% can be used to compare assembly
results from different samples or studies, the cross-comparisons of which cannot
be performed with N50.
PMID- 28418727
TI - Poor Sleep Is Associated With Greater Marital Aggression: The Role of Self
Control.
AB - BACKGROUND/OBJECTIVE: Although sleep problems are linked to relationship
difficulties, the mechanisms involved have not been empirically demonstrated. The
present study considers self-control as such a mechanism. PARTICIPANTS: Data were
collected from 342 predominantly white, middle-class, married adults. METHOD:
Participants completed online questionnaires about sleep, marital aggression, and
self-control, and a virtual voodoo doll task. RESULTS AND CONCLUSIONS: Sleep
problems were associated with higher levels of aggression on all measures, and
lower self-control mediated these associations. Associations did not depend on
participant gender, presence of children in the home, income, or length of
marriage.
PMID- 28418728
TI - Prevalence and Predictors of Food Insecurity among People Living with HIV
Enrolled in Antiretroviral Therapy and Livelihood Programs in Two Rural Zambian
Hospitals.
AB - The objective of this study was to examine the prevalence and predictors of food
insecurity among people living with HIV (PLHIV) in two rural communities in
Zambia. A cross-sectional sample of 101 PLHIV was surveyed using the Household
Food Insecurity Access Scale. In multivariable linear regression models, income,
household possessions, and perceived coping strategies were significantly
associated with decreased food insecurity. Debt and perceived mental distress
were significantly associated with increased food insecurity. Programs that
tackle economic disadvantage and its adverse effect on stress may be an
appropriate strategy to improve food security of PLHIV in low-resource
communities.
PMID- 28418729
TI - Relationship of cognitive functions and gross motor abilities in children with
spastic diplegic cerebral palsy.
AB - Spastic diplegic cerebral palsy can be accompanied by a myriad of symptoms
affecting other body systems including cognitive dysfunction. The purpose of this
study was to determine whether a relationship exists between cognitive functions
in the form of selective attention and figural memory domains with standing and
walking motor abilities in children with diplegic cerebral palsy. The research
design was a correlational study. Tasks assessing cognitive function and gross
motor abilities were carried out with a sample of 50 children. The data
demonstrated the presence of correlation between selective attention and figural
memory domains of cognitive function with standing, walking running, and jumping
subscales of the Gross Motor Function Measure (GMFM) scale at different ages, and
this correlation was significant between selective attention domain and gross
motor abilities. The outcome measurements of the current study provide original
evidence based on the necessity of including cognitive and physical impairments
in the examination and evaluation of children with diplegic cerebral palsy in
research and clinical settings.
PMID- 28418730
TI - Patient Inputs for Mobile Health Systems for Type 1 Diabetes Care.
PMID- 28418731
TI - Why Do Some Concentrated Insulins Maintain Their
Pharmacokinetics/Pharmacodynamics Profile?
PMID- 28418732
TI - Insulin Infusion Sets and Continuous Glucose Monitoring Sensors: Where the
Artificial Pancreas Meets the Patient.
PMID- 28418733
TI - Feasibility of SPECT-CT Imaging to Study the Pharmacokinetics of Antisense
Oligonucleotides in a Mouse Model of Duchenne Muscular Dystrophy.
AB - Antisense oligonucleotides (AONs) are promising candidates for treatment of
Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in
premature death. However, more knowledge on the pharmacokinetics of new AON drug
candidates is desired for effective application in the clinic. We assessed the
feasibility of using noninvasive single-photon emission computed tomography
computed tomography (SPECT-CT) imaging to determine AON pharmacokinetics in vivo.
To this end, a 2'-O-methyl phosphorothioate AON was radiolabeled with 123I or
111In, and administered to mdx mice, a rodent model of DMD. SPECT-CT imaging was
performed to determine AON tissue levels, and the results were compared to data
obtained with invasive analysis methods (scintillation counting and a ligation
hybridization assay). We found that SPECT-CT data obtained with 123I-AON and
111In-AON were qualitatively comparable to data derived from invasive analytical
methods, confirming the feasibility of using SPECT-CT analysis to study AON
pharmacokinetics. Notably, also AON uptake in skeletal muscle, the target tissue
in DMD, could be readily quantified using SPECT-CT imaging, which was considered
a particular challenge in mice, due to their small size. In conclusion, our
results demonstrate that SPECT-CT imaging allows for noninvasive characterization
of biodistribution and pharmacokinetics of AONs, thereby enabling quantitative
comparisons between different radiolabeled AON drug candidates and qualitative
conclusions about the corresponding unmodified parent AONs. This technology may
contribute to improved (pre)clinical drug development, leading to drug candidates
with optimized characteristics in vivo.
PMID- 28418734
TI - Bunyaviridae RdRps: structure, motifs, and RNA synthesis machinery.
AB - Bunyaviridae family is the largest and most diverse family of RNA viruses. It has
more than 350 members divided into five genera: Orthobunyavirus, Phlebovirus,
Nairovirus, Hantavirus, and Tospovirus. They are present in the five continents,
causing recurrent epidemics, epizootics, and considerable agricultural loss. The
genome of bunyaviruses is divided into three segments of negative single-stranded
RNA according to their relative size: L (Large), M (Medium) and S (Small)
segment. Bunyaviridae RNA-dependent RNA polymerase (RdRp) is encoded by the L
segment, and is in charge of the replication and transcription of the viral RNA
in the cytoplasm of the infected cell. Viral RdRps share a characteristic right
hand-like structure with three subdomains: finger, palm, and thumb subdomains
that define the formation of the catalytic cavity. In addition to the N-terminal
endonuclease domain, eight conserved motifs (A-H) have been identified in the
RdRp of Bunyaviridae. In this review, we have summarized the recent insights from
the structural and functional studies of RdRp to understand the roles of
different motifs shared by RdRps, the mechanism of viral RNA replication, genome
segment packaging by the nucleoprotein, cap-snatching, mRNA transcription, and
other RNA mechanisms of bunyaviruses.
PMID- 28418735
TI - Polymorphisms of COMT (c.649G>A), MAO-A (c.1460C>T), NET (c.1287G>A) Genes and
the Level of Catecholamines, Serotonin in Patients with Parkinson's Disease.
AB - The purpose of this study was to determine the concentration of plasma
norepinephrine (NE), epinephrine (E), and serotonin (5-HT) in two collections,
after a 30-min supine (I) and 5-min upright position (II), and polymorphisms of
genes, COMT (c.649G>A), MAO-A (c.1460C>T), and NET (c.1287G>A), in patients with
Parkinson's disease (PD) and other degenerative parkinsonism and controls. The
study was performed in 49 PD patients, 19 parkinsonism patients, and 48 controls.
The level of NE, E, and 5-HT was determined by HPLC/EC. PCR-RFLP was conducted to
analyze the COMT, MAO-A, and NET polymorphisms. Genotypes of COMT, MAO-A, and NET
genes occurred with different frequencies in patients with movement disorders and
controls. NET AA occurred 4.8 times more frequently in patients with parkinsonism
than in PD (p < 0.05). COMT AA genotype was associated with increased E levels [E
(I) p < 0.01, E (II) p < 0.05] in PD compared to controls. Patients with
parkinsonism with MAO-A TT genotype have a significantly higher level of 5-HT [5
HT (II), p < 0.05] compared to controls. Moreover, PD patients with NET GA
genotype have the lowest level of NE (p < 0.05) compared to controls. It appears
that COMT, MAO-A, and NET polymorphisms and levels of NE, E, and 5-HT are
involved in pathogenesis of PD.
PMID- 28418736
TI - Curricular Time, Patient Exposure, and Comfort Caring for Lesbian, Gay, Bisexual,
and Transgender Patients Among Recent Medical Graduates.
PMID- 28418737
TI - Public Health Emergency Response in Taiwan.
AB - In recent years, growth of international travel and trade, as well as climate
change, has resulted in the frequent emergence and reemergence of infectious
diseases such as Ebola, Zika, and MERS. In 2016, Taiwan used the Joint External
Evaluation (JEE) tool to evaluate its public health emergency response capacities
and understand important areas for improvement. This article presents Taiwan's
disaster and public health emergency response organizational structure, real-time
integrated information, response processes, and command center structure. After
reviewing the results of the JEE tool and drawing lessons from emergency response
efforts in the United States, we provide 3 recommendations that may enhance
Taiwan's public health emergency response capacities: establish common principles
for disaster response regardless of which agency is in charge, standardize
operation procedures, and perform regular training that includes nongovernmental
organizations and a range of government departments.
PMID- 28418738
TI - Real-Time Surveillance of Infectious Diseases: Taiwan's Experience.
AB - Integration of multiple surveillance systems advances early warning and supports
better decision making during infectious disease events. Taiwan has a
comprehensive network of laboratory, epidemiologic, and early warning
surveillance systems with nationwide representation. Hospitals and clinical
laboratories have deployed automatic reporting mechanisms since 2014 and have
effectively improved timeliness of infectious disease and laboratory data
reporting. In June 2016, the capacity of real-time surveillance in Taiwan was
externally assessed and was found to have a demonstrated and sustainable
capability. We describe Taiwan's disease surveillance system and use surveillance
efforts for influenza and Zika virus as examples of surveillance capability.
Timely and integrated influenza information showed a higher level and extended
pattern of influenza activity during the 2015-16 season, which ensured prompt
information dissemination and the coordination of response operations. Taiwan
also has well-developed disease detection systems and was the first country to
report imported cases of Zika virus from Miami Beach and Singapore. This
illustrates a high level of awareness and willingness among health workers to
report emerging infectious diseases, and highlights the robust and sensitive
nature of Taiwan's surveillance system. These 2 examples demonstrate the
flexibility of the surveillance systems in Taiwan to adapt to emerging infectious
diseases and major communicable diseases. Through participation in the GHSA,
Taiwan can more actively collaborate with national counterparts and use its
expertise to strengthen global and regional surveillance capacity in the Asia
Pacific and in Southeast Asia, in order to advance a world safe and secure from
infectious disease.
PMID- 28418740
TI - Immunoassays for Field Screening of Bacillus anthracis and Ricin.
PMID- 28418739
TI - The Joint External Evaluation of Taiwan: The External Evaluators' Perspective.
AB - A team of experts from the Johns Hopkins Center for Health Security conducted an
independent external assessment of Taiwan's capabilities under the International
Health Regulations 2005 (IHR), using the IHR Joint External Evaluation (JEE) tool
adopted by the World Health Organization and the Global Health Security Agenda.
In this article we describe the methods and process of the assessment, identify
lessons learned, and make recommendations for the government of Taiwan, the JEE
process, and the JEE tool.
PMID- 28418741
TI - Implementation of the IHR Joint External Evaluation: Taiwan's Experiences.
AB - In February 2016, the World Health Organization developed the Joint External
Evaluation (JEE) tool to independently assess country capacity to prevent,
detect, and respond to public health threats as part of the International Health
Regulations (IHR) (2005) monitoring and evaluation framework. In light of this,
the Taiwan government actively engaged at least 19 government agencies or
institutions and voluntarily implemented the JEE. An External Assessment Team
consisting of 6 US subject matter experts conducted the external evaluation,
including site visits, from June 21 to July 1, 2016. The results, published on
October 18, 2016, are useful and will be translated into actions and change in
the system. Based on Taiwan's experiences, early stakeholder engagement and an
experts' pre-JEE pilot visit would contribute to a successful JEE process.
PMID- 28418743
TI - Stockpile Model of Personal Protective Equipment in Taiwan.
AB - The Taiwan Centers for Disease Control (Taiwan CDC) has established a 3-tier
personal protective equipment (PPE) stockpiling framework that could maintain a
minimum stockpile for the surge demand of PPE in the early stage of a pandemic.
However, PPE stockpiling efforts must contend with increasing storage fees and
expiration problems. In 2011, the Taiwan CDC initiated a stockpile replacement
model in order to optimize the PPE stockpiling efficiency, ensure a minimum
stockpile, use the government's limited funds more effectively, and achieve the
goal of sustainable management. This stockpile replacement model employs a first
in-first-out principle in which the oldest stock in the central government
stockpile is regularly replaced and replenished with the same amount of new and
qualified products, ensuring the availability and maintenance of the minimum
stockpiles. In addition, a joint electronic procurement platform has been
established for merchandising the replaced PPE to local health authorities and
medical and other institutions for their routine or epidemic use. In this
article, we describe the PPE stockpile model in Taiwan, including the 3-tier
stockpiling framework, the operational model, the components of the replacement
system, implementation outcomes, epidemic supports, and the challenges and
prospects of this model.
PMID- 28418742
TI - Taiwan's Public Health National Laboratory System: Success in Influenza Diagnosis
and Surveillance.
AB - Taiwan's National Laboratory System is one of the action packages of the Global
Health Security Agenda, which was launched by the World Health Organization (WHO)
to promote health security as an international priority and to encourage progress
toward full implementation of the WHO International Health Regulations (IHR)
2005. The mission of each national laboratory system is to conduct real-time
biosurveillance and effective laboratory-based diagnostics, as measured by a
nationwide laboratory system able to reliably conduct diagnoses on specimens
transported properly to designated laboratories from at least 80% of the regions
in the country. In Taiwan, the national laboratory system for public health is
well-established and coordinated by the Taiwan Centers for Disease Control (CDC),
which is the government authority in charge of infectious disease prevention and
intervention. Through the national laboratory system, Taiwan CDC effectively
detects and characterizes pathogens that cause communicable diseases across the
entire country, including both known and novel threats, and also conducts
epidemiologic analyses of infectious diseases. In this article, we describe the
national laboratory system for public health in Taiwan. We provide additional
information on the national influenza laboratory surveillance network to
demonstrate how our national laboratory systems work in practice, including
descriptions of long-term seasonal influenza characterization and successful
experiences identifying novel H7N9 and H6N1 influenza viruses.
PMID- 28418744
TI - Taiwan's Travel and Border Health Measures in Response to Zika.
AB - Zika virus has recently emerged as a worldwide public health concern. Travel and
border health measures stand as one of the main strategies and frontline defenses
in responding to international epidemics. As of October 31, 2016, Taiwan has
reported 13 imported cases, 5 of which were detected through routine entry
screening and active monitoring at international airports. This article shares
Taiwan's disease surveillance activities at designated points of entry and travel
and border health measures in response to Zika. The Taiwan government
collaborates with its tourism industry to disseminate information about
precautionary measures and encourages tour guides to report suspected individuals
or events to activate early response measures. Taiwan also engages in vector
control activities at points of entry, including targeting aircraft from
countries where vector-borne diseases are endemic, implementing mosquito sweep
measures, and collecting vector surveillance data. In future emerging and
reemerging disease events, entry surveillance at designated points of entry may
enable early detection of diseases of international origin and more rapid
activation of public health preparedness activities and international
collaboration. Taiwan will continue to maximize border and travel health measures
in compliance with IHR (2005) requirements, which rely on continued risk
assessment, practical implementation activities, and engagement with all
stakeholders.
PMID- 28418745
TI - Taiwan's Experience in Hospital Preparedness and Response for Emerging Infectious
Diseases.
AB - The Communicable Disease Control Medical Network (CDCMN), established in 2003
after the SARS outbreak in Taiwan, has undergone several phases of modification
in structure and activation. The main organizing principles of the CDCMN are
centralized isolation of patients with severe highly infectious diseases and
centralization of medical resources, as well as a network of designated regional
hospitals like those in other countries. The CDCMN is made up of a command
system, responding hospitals, and supporting hospitals. It was tested and
activated in response to the H1N1 influenza pandemic in 2009-10 and the Ebola
outbreak in West Africa in 2014-2016, and it demonstrated high-level functioning
and robust capacity. In this article, the history, structure, and operation of
the CDCMN is introduced globally for the first time, and the advantages and
challenges of this system are discussed. The Taiwanese experience shows an
example of a collaboration between the public health system and the medical
system that may help other public health authorities plan management and hospital
preparedness for highly infectious diseases.
PMID- 28418747
TI - Promoting Health Security: Potential, Role, and Future Directions of a Medical
University.
PMID- 28418746
TI - Risk and Outbreak Communication: Lessons from Taiwan's Experiences in the Post
SARS Era.
AB - In addition to the impact of a disease itself, public reaction could be
considered another outbreak to be controlled during an epidemic. Taiwan's
experience with SARS in 2003 highlighted the critical role played by the media
during crisis communication. After the SARS outbreak, Taiwan's Centers for
Disease Control (Taiwan CDC) followed the WHO outbreak communication guidelines
on trust, early announcements, transparency, informing the public, and planning,
in order to reform its risk communication systems. This article describes the
risk communication framework in Taiwan, which has been used to respond to the
2009-2016 influenza epidemics, Ebola in West Africa (2014-16), and MERS-CoV in
South Korea (2015) during the post-SARS era. Many communication strategies,
ranging from traditional media to social and new media, have been implemented to
improve transparency in public communication and promote civic engagement. Taiwan
CDC will continue to maintain the strengths of its risk communication systems and
resolve challenges as they emerge through active evaluation and monitoring of
public opinion to advance Taiwan's capacity in outbreak communication and
control. Moreover, Taiwan CDC will continue to implement the IHR (2005) and to
promote a global community working together to fight shared risks and to reach
the goal of "One World, One Health."
PMID- 28418749
TI - An improved technique for obtaining well-spread metaphases from plants with
numerous large chromosomes.
AB - Preparations that contain well-spread metaphase chromosomes are critical for
plant cytogenetic analyses including chromosome counts, banding procedures, in
situ hybridization, karyotyping and construction of ideograms. Chromosome
spreading is difficult for plants with large and numerous chromosomes. We report
here a technique for obtaining cytoplasm-free, well-spread metaphases from two
Amaryllidaceae species: Sprekelia formosissima (2n = 120) and Hymenocallis
howardii (2n = 96). The technique has three main steps: 1) pretreatment to cause
chromosome condensation, 2) dripping onto tilted slides coated with a thin layer
of pure acetic acid and 3) application of steam and acetic acid to produce
cytoplasmic hydrolysis, which spreads the chromosomes.
PMID- 28418750
TI - Comparing Asian American Women's Knowledge, Self-Efficacy, and Perceived Risk of
Heart Attack to Other Racial and Ethnic Groups: The mPED Trial.
AB - OBJECTIVE: The aim of the study was to compare knowledge and awareness of heart
attacks/heart disease and perceived risk for future heart attack in Asian/Pacific
Islander women, compared to other racial and ethnic groups. MATERIALS AND
METHODS: In this cross-sectional study, 318 women enrolled in a mobile phone
based physical activity education trial were analyzed. Heart attack knowledge,
self-efficacy for recognizing and responding to heart attack symptoms, and
perceived risk for a future heart attack were measured. Analyses were conducted
using logistic, proportional odds, and linear regression models, depending on the
outcome and adjusting for age. Pairwise differences between Asian/Pacific
Islanders and the other four groups were assessed using a Bonferroni correction
(p < 0.0125). RESULTS: Asian/Pacific Islander women had significantly lower total
scores for knowledge of heart attack and self-efficacy for heart attack
recognition and care seeking behavior compared to the Caucasian women (p = 0.001
and p = 0.002, respectively). However, perceived risk did not differ among the
groups. Forty-six percent of the Asian American women, compared to 25% of
Caucasian women, falsely believed "breast cancer is the number one cause of death
for women (p = 0.002)." In addition, Asian/Pacific Islander women were less
likely to report "arm pain, numbness, tingling, or radiating" as one of the heart
attack symptoms compared to the Caucasian and the multiracial group (34%, 63% [p
< 0.001], and 66% [p = 0.004], respectively). CONCLUSIONS: These findings
highlight the urgent need to develop effective, tailored campaigns to close the
knowledge gap between Asian/Pacific Islander women and Caucasian women.
PMID- 28418751
TI - Influence of Exergaming on the Perception of Cancer-Related Fatigue.
AB - OBJECTIVE: Exercise is recommended for cancer patients to reduce fatigue and
improve quality of life. This study's aim is to evaluate the influence of an
exergaming protocol on cancer-related fatigue, muscle fatigue, and muscle
strength in cancer patients. MATERIALS AND METHODS: We conducted a quasi
experimental control study using exergaming in all groups through an Xbox360
KinectTM console, two to three times per week, for 20 sessions. Three groups were
created: cancer patients in chemotherapy and/or radiotherapy group (CRG; n:15),
cancer patients after chemotherapy and/or radiotherapy (CAG; n:15), and a control
group (CG; n:15). They were assessed for cancer-related fatigue using the fatigue
subscale of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT
F) questionnaire. To assess dorsiflexor and plantar flexor muscle functioning, we
used median frequency (MDF) of the surface electromyography and muscle strength
using a dynamometer. The assessments were performed preintervention (EV0), after
10 sessions (EV1), and after 20 sessions (EV2). RESULTS: With an exergaming
protocol, CRG and CAG showed a reduction in related fatigue compared with CG (P <
0.01). The CRG group saw an increase in maximal voluntary isometric contraction
in right plantar flexor muscles and dorsiflexor muscles, as well as an increase
in the MDF of both medial gastrocnemius muscles and the left tibialis anterior
muscle of the CAG. For other analyses done, the differences were observed during
exergaming. CONCLUSIONS: Exergaming demonstrated efficacy in reducing cancer
patients' fatigue, including muscle fatigue, and increasing muscle strength in
patients' legs.
PMID- 28418752
TI - A Pilot Study of the Attractive Features of Active Videogames Among Chinese
Primary School Children.
AB - OBJECTIVE: The present study (1) explored the attractive features that affect
Chinese primary school children's preferences of active videogames (AVGs) and (2)
contrasted these findings with those in the Western literature. PARTICIPANTS AND
METHODS: A total of 22 Chinese primary school children were recruited and
interviewed. Four AVGs (Wii "Boxing," "Wii FitTM Plus Obstacle Run"; "EyeToy
Knockout", "EyeToy Keep ups") from two commercial consoles (Nintendo(r) WiiTM and
Sony PlayStation(r) 2 "EyeToy(r)") were employed. Participants used four selected
AVGs for 3 minutes each. After each play period, children (1) described the
strengths and weaknesses of each game as well as rated the attractive features of
each game based on a 16-item questionnaire and (2) rated up to 5 items that were
most influential regarding their AVG preferences. RESULTS: Participants indicated
that control was the most significant feature, followed by feedback, goal, and
graphics. The top five rated features imply that the perception of competence was
the most appealing aspect and expected outcome of Chinese children who play AVGs.
CONCLUSIONS: Compared with the Western findings regarding attractive AVG
features, the present study found certain similarities as well as significant
differences among Chinese AVG players. Based on the present study, control,
feedback, goal, and graphics are the most significant features that attract
Chinese children to play AVGs. Physical exertion, social interaction,
competition, and learning outcomes, which are valued according to Western
studies, were not mentioned as significant features by Chinese children. These
findings demonstrate a need to investigate the effect of cultural background in
AVG study design.
PMID- 28418753
TI - Intraosseous Pressure Monitoring in Healthy Volunteers.
AB - STUDY OBJECTIVE: Invasively monitoring blood pressure through the IO device has
not been thoroughly demonstrated. This study attempted to establish baseline
values of IO pressure in a healthy human population. METHODS: This was a
prospective, healthy volunteer, observational study. Participants had two IO
devices placed (humerus and tibia), and participant IO pressures, vital signs,
and pain scores were monitored for up to 60 minutes. Participants were contacted
at 24-hours and 7 days post-testing to assess for adverse events. Summary
statistics were calculated for systolic, diastolic, and mean humeral and tibial
IO pressure. The ratio of IO to non-invasive blood pressure was calculated, and
Bland Altman plots were created. The slope (linear) of the mean humeral and the
tibial IO pressures were also calculated. RESULTS: Fifteen subjects were enrolled
between April and July 2015. Fourteen of 15 humeral IOs were placed successfully
(93.3%) and all 15 of the tibial IOs were placed successfully. Mean tibial
systolic, diastolic, and mean IO pressure were 55.8 +/- 27.9, 49.3 +/- 27.1, and
48.4 +/- 29.4 mm Hg, respectively. Humeral systolic, diastolic, and mean IO
pressure were 32.9 +/- 16.0, 27.4 +/- 15.2, and 24.5 +/- 14.3 mm Hg. The mean
tibial IO pressure was 52.5% +/- 32.0% of external cuff pressure ratio. The mean
humeral IO pressure was 26.5% +/- 15.2% of the external mean blood pressure. The
Bland Altman plots showed an inconsistent relationship between the systolic and
diastolic cuff pressure and the IO pressures. We observed a 1% per minute
decrease in IO pressure from the initial placement until the final reading.
CONCLUSIONS: Intraosseous pressure readings can be obtained in healthy human
volunteers. However, absolute IOP values were not consistent between subjects.
Future research may determine how IO pressure can be used to guide therapy in ill
and injured patients.
PMID- 28418754
TI - Evaluating the Effect of Virtual Reality Temporal Bone Simulation on
Mastoidectomy Performance: A Meta-analysis.
AB - Background The increasing prevalence of virtual reality simulation in temporal
bone surgery warrants an investigation to assess training effectiveness.
Objectives To determine if temporal bone simulator use improves mastoidectomy
performance. Data Sources Ovid Medline, Embase, and PubMed databases were
systematically searched per the PRISMA guidelines. Review Methods Inclusion
criteria were peer-reviewed publications that utilized quantitative data of
mastoidectomy performance following the use of a temporal bone simulator. The
search was restricted to human studies published in English. Studies were
excluded if they were in non-peer-reviewed format, were descriptive in nature, or
failed to provide surgical performance outcomes. Meta-analysis calculations were
then performed. Results A meta-analysis based on the random-effects model
revealed an improvement in overall mastoidectomy performance following training
on the temporal bone simulator. A standardized mean difference of 0.87 (95% CI,
0.38-1.35) was generated in the setting of a heterogeneous study population ( I2
= 64.3%, P < .006). Conclusion In the context of a diverse population of virtual
reality simulation temporal bone surgery studies, meta-analysis calculations
demonstrate an improvement in trainee mastoidectomy performance with virtual
simulation training.
PMID- 28418755
TI - Recommendations for Adopting the International Code of Marketing of Breast-milk
Substitutes Into U.S. Policy.
AB - In 1981, the World Health Organization adopted the International Code of
Marketing of Breast-milk Substitutes ( International Code), with subsequent
resolutions adopted since then. The International Code contributes to the safe
and adequate provision of nutrition for infants by protecting and promoting
breastfeeding and ensuring that human milk substitutes, when necessary, are used
properly through adequate information and appropriate marketing and distribution.
Despite the World Health Organization recommendations for all member nations to
implement the International Code in its entirety, the United States has yet to
take action to translate it into any national measures. In 2012, only 22.3% of
infants in the United States met the American Academy of Pediatrics
recommendation of at least 6 months of exclusive breastfeeding. Countries
adopting legislation reflecting the provisions of the International Code have
seen increases in breastfeeding rates. This article discusses recommendations for
translating the International Code into U.S. policy. Adopting legislation that
implements, monitors, and enforces the International Code in its entirety has the
potential to contribute to increased rates of breastfeeding in the United States,
which can lead to improved health outcomes in both infants and breastfeeding
mothers.
PMID- 28418757
TI - Visual Circuits for Direction Selectivity.
AB - Images projected onto the retina of an animal eye are rarely still. Instead, they
usually contain motion signals originating either from moving objects or from
retinal slip caused by self-motion. Accordingly, motion signals tell the animal
in which direction a predator, prey, or the animal itself is moving. At the
neural level, visual motion detection has been proposed to extract directional
information by a delay-and-compare mechanism, representing a classic example of
neural computation. Neurons responding selectively to motion in one but not in
the other direction have been identified in many systems, most prominently in the
mammalian retina and the fly optic lobe. Technological advances have now allowed
researchers to characterize these neurons' upstream circuits in exquisite detail.
Focusing on these upstream circuits, we review and compare recent progress in
understanding the mechanisms that generate direction selectivity in the early
visual system of mammals and flies.
PMID- 28418756
TI - Cultured microbes represent a substantial fraction of the human and mouse gut
microbiota.
AB - During the last 15 years, molecular techniques have been preferred over culture
based approaches for the study of mammalian gut microbiota, i.e. the communities
of microorganisms dwelling in the intestine of mammals. The main reason is the
belief that the majority of gut bacteria, especially strict anaerobes, escape
cultivation. Despite numerous such statements in publications, the literature
does not provide a clear overview on the subject. In the present manuscript, we
highlight recent work on the cultivation of bacteria from the intestine of
mammals, review the literature and provide novel data pertaining to cultured
fractions of mammalian gut microbiota. These data show that, despite marked inter
sample variations, 35 to 65% of molecular species detected by sequencing have
representative strains in culture.
PMID- 28418758
TI - Inhaled Heparin: Therapeutic Efficacy and Recent Formulations.
AB - Heparin is well known for its anticoagulant and anti-inflammatory properties.
Inhaled heparin regimens are increasingly being used to manage lung disease. It
has been used to treat cystic fibrosis, thromboembolism, and pulmonary fibrosis,
as well as bronchial asthma and asthma-induced airway hypersensitivity. Several
preclinical studies attained some useful effects of heparin-administered,
parenterally and through inhalation, treatment of lung disease. Besides, recent
clinical trials suggest that inhaled heparin for lung diseases is beneficial and
safe, but such data remain to be limited. In 2005, the orphan designation was
granted by the European Commission for heparin sodium (inhalation use) for the
treatment of cystic fibrosis. The positive results of heparin in the pulmonary
route necessitate a focus on the preparation and evaluation of heparin in
advanced drug delivery systems, namely nano/microparticles and liposomes. Through
this pulmonary delivery, heparin is protected from enzymatic degradation within
the airway. Heparin is thus passively targeted into the lungs, and long-lasting
localized treatment is achieved. On the other hand, these systems have
encountered several problems as follows: (1) polymers, such as poly-L-lactide
glycolic acid, poly (lactic acid), and chitosan, used to prepare heparin-loaded
microparticle/nanoparticle (MP/NP) systems have not been granted approval for
lung application by the FDA and (2) liposomal and NP formulation stability is the
main problem of formulation design. We propose that additional in vitro and in
vivo research is necessary to assess the clinical applicability of this treatment
strategy. The present article discusses heparin treatments for lung diseases and
the use of heparin and/or heparin-loaded drugs in advanced delivery systems
through the pulmonary route.
PMID- 28418759
TI - Virulence profile: Swaine L. Chen.
PMID- 28418760
TI - Aromatic dipeptide Trp-Ala can be transported by Arabidopsis peptide transporters
AtPTR1 and AtPTR5.
AB - Dipeptides with an aromatic residue at the N-terminal position induced lower
inward currents or blocked leak currents in Xenopus oocytes expressing the proton
coupled peptide transporter AtPTR1 or AtPTR5 of Arabidopsis thaliana compared
with dipeptides with an aromatic residue at the C-terminal position. Here, AtPTR1
and AtPTR5 were expressed in a yeast mutant of peptide transporter (ptr2) with
tryptophan auxotrophy. Growth assays showed that Trp-Ala could be transported by
both AtPTR1 and AtPTR5 as efficiently as Ala-Trp. Our data suggested that the
previous finding in Xenopus oocytes might be an artifact of heterologous
expression, and that AtPTR1 and AtPTR5 expressed in yeast could transport
dipeptides with an aromatic residue at the N-terminal position.
PMID- 28418761
TI - Economic Evaluation of a Hospital-Based Palliative Care Program.
AB - PURPOSE: Establish costs of an inpatient palliative care unit (PCU) and conduct a
threshold analysis to estimate the maximum possible costs for the PCU to be
considered cost effective. METHODS: We used a hospital perspective to determine
costs on the basis of claims from administrative data from Johns Hopkins PCU
between March 2013 and March 2014. Using existing literature, we estimated the
number of quality-adjusted life years (QALYs) that the PCU could generate. We
conducted a threshold analysis to assess the maximum costs for the PCU to be
considered cost effective, incorporating willingness to pay ($180,000 per QALY).
Three types of costs were considered, which included variable costs alone,
contribution margin (ie, revenue minus variable costs), and PCU cost savings
compared with usual care (from a separate publication). RESULTS: The data showed
that there were 153 patient encounters (PEs), variable costs of $1,050,031
($1,343 per PE per day), a contribution margin of $318,413 ($407 per PE per day),
and savings compared with usual care of $353,645 ($452 savings per PE per day).
On the basis of the literature, the program could generate 3.11 QALYs from PEs
(0.05 QALY) and caregivers (3.06 QALYs). The threshold analysis determined that
the maximum variable cost required to be cost effective was $559,800 (an
additional $716 per PE per day could be spent). CONCLUSION: According to variable
costs, the PCU was not cost effective; however, when considering savings of the
PCU compared with usual care, the PCU was cost saving. The contribution margin
showed that the PCU was cost saving. This study supports efforts to expand PCUs,
which enhance care for patients and their caregivers and can generate hospital
savings. Future research should prospectively explore the cost utility of PCUs.
PMID- 28418762
TI - Challenges Persist Under Americans With Disabilities Act Amendments Act: How Can
Oncology Providers Help?
AB - PURPOSE: To determine whether the Amendments to the hallmark Americans with
Disabilities Act (ADA; effective January 2009), which provide increased access to
the antidiscrimination laws for many with chronic illness, are related to changes
in workplace discrimination allegations in individuals with a history of cancer.
METHODS: Information collected by the Equal Employment Opportunities Commission
was used to compare allegations of discrimination and their merit before (2001 to
2008) and after (2009 to 2011) implementation of the Amendments Act. RESULTS:
Allegations related to terms of employment (eg, promotions, wages) were more
likely to be filed (odds ratio [OR], 1.34; 95% CI, 1.11 to 1.61) and determined
to have merit (OR, 1.35; 95% CI, 1.03 to 1.77) after implementation of the
Amendments Act. Allegations related to workplace relations (eg, harassment,
discipline, discharge) were also more likely to be filed post Amendments Act (OR,
1.48; 95% CI, 1.23 to 1.78), although the merit of this complaint remained
stable. Filing of all other allegations of discrimination (ie, hiring, reasonable
accommodation, and termination) and their merit remained unchanged post
Amendments Act. CONCLUSION: Despite the implementation of the Amendments Act,
discrimination allegations in those with a history of cancer persisted or in
certain areas increased. Although prevention of workplace discrimination rests
primarily with employers, the oncology care team is uniquely qualified to provide
information related to residual symptoms and function that can facilitate more
personalized solutions to workplace discrimination, such as successful workplace
accommodations. Information is provided that can assist the oncology team in
their efforts to improve work outcomes.
PMID- 28418763
TI - Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma:
Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11
Trials.
AB - Purpose Combined-modality treatment is widely considered the standard of care in
early-stage Hodgkin lymphoma (HL), and treatment intensity has been reduced over
the last years. Long-term follow-up is important to judge both efficacy and
safety of the different therapies used. Patients and Methods We analyzed updated
follow-up data on 4,276 patients treated within the German Hodgkin Study Group
trials HD7 and HD10 for early-stage favorable HL and HD8 and HD11 for early-stage
unfavorable HL between 1993 and 2003. Results In HD7 (N = 627; median follow-up,
120 months), combined-modality treatment was superior to extended-field
radiotherapy (RT), with 15-year progression-free survival (PFS) of 73% versus 52%
(hazard ratio [HR], 0.5; 95% CI, 0.3 to 0.6; P < .001), without differences in
overall survival (OS). In HD10 (N = 1,190; median follow-up, 98 months),
noninferiority of two cycles of doxorubicin, bleomycin, vinblastine, dacarbazine
(ABVD) plus 20 Gy involved-field (IF)-RT to more intensive four cycles of ABVD
plus 30 Gy IF-RT was confirmed with 10-year PFS of 87% each (HR, 1.0; 95%, 0.6 to
1.5) and OS of 94% each (HR, 0.9; 95% CI, 0.5 to 1.6), respectively. In both
trials, no differences in second neoplasias were observed. In HD8 (N = 1,064;
median follow-up, 153 months), noninferiority of involved-field RT to extended
field RT regarding PFS was confirmed (HR, 1.0; 95% CI, 0.8 to 1.2). In HD11 (N =
1,395; median follow-up, 106 months), superiority of bleomycin, etoposide,
doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at
baseline over ABVD was not observed. After BEACOPPbaseline, 20 Gy IF-RT was
noninferior to 30 Gy (10-year PFS, 84% v 84%; HR, 1.0; 95% CI, 0.7 to 1.5). In
contrast, PFS was inferior in ABVD-treated patients receiving 20 Gy instead of 30
Gy IF-RT (10-year PFS, 76% v 84%; HR, 1.5; 95% CI, 1.0 to 2.1). No differences in
OS or second neoplasias were observed in in both trials. Conclusion Long-term
follow-up data of the four randomized trials largely support the current risk
adapted therapeutic strategies in early-stage HL. Nevertheless, continued follow
up is necessary to assess the long-term safety of currently applied therapeutic
strategies.
PMID- 28418764
TI - Disease Surveillance of California Ground Squirrels ( Spermophilus beecheyi ) in
a Drive-through Zoo in Oregon, USA.
AB - Rodents and other small wild mammals are often considered to be pests and vectors
for disease in zoos that house small populations of valuable threatened and
endangered animals. In 2005, three nonhuman primates at a drive-through zoo in
Oregon, US, acquired tularemia from an unknown source. Due to an abundance of
California ground squirrels ( Spermophilus beecheyi ) on zoo grounds, we
instituted serosurveillance of this species from July through September 2008 to
determine the prevalence of antibodies against pathogens considered to be
potentially transmissible to collection animals. Serologic testing was performed
for Francisella tularensis ; Leptospira interrogans serovars Canicola,
Grippotyphosa, Hardjo, Icterohemorrhagiae, and Pomona; Toxoplasma gondii ; and
Yersinia pestis . All squirrels were seronegative for Yersinia pestis (0%; 0/45)
and Toxoplasma gondii (0%; 0/20); there was a prevalence of 2% (1/45) for
Francisella tularensis antibodies and 57% (24/42) were positive for various
Leptospira serovars. Although it remains unclear whether ground squirrels present
a significant risk for transmission of disease to zoo animals, vaccination of
high-risk zoo animals against leptospirosis warrants consideration. Beyond this,
continued vigilance and persistence with various forms of pest control may reduce
the likelihood of disease transmission from wildlife hosts to animals in human
care.
PMID- 28418765
TI - Brucella ceti Infection in a Common Minke Whale ( Balaenoptera acutorostrata )
with Associated Pathology.
AB - There are three major lineages of marine mammal strains of Brucella spp.:
Brucella ceti ST23, found predominantly in porpoises; B. ceti ST26, in pelagic
delphinids and ziphiids; and Brucella pinnipedialis ST24/25, predominantly in
seals. The isolation of Brucella spp. in mysticetes has been described only in
common minke whales ( Balaenoptera acutorostrata ) in Norway and Scotland. We
report a third case of Brucella infection and isolation in a minke whale
associated with a large abscess. In contrast to the two previous reports that
involved isolates of B. pinnipedialis ST24 or the porpoise-associated B. ceti
complex ST23, this case was associated with the dolphin-associated B. ceti ST26.
Thus, minke whales can be infected naturally with members of all the distinct
major lineages of Brucella associated with marine mammals. This report is unique
in that the B. ceti ST26 did not originate from a pelagic delphinid or a beaked
whale.
PMID- 28418766
TI - Clinical Phenotype of Depression Affects Interleukin-6 Synthesis.
AB - Major depressive disorder (MDD) is not a single disease, but a number of various
ailments that form one entity. Psychomotor retardation, anhedonia, sleep
disorders, an increased suicide risk, and anxiety are the main symptoms that
often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one
of the proinflammatory cytokines, seems to be overexpressed during certain mental
disorders, including MDD. Overexpression of IL-6 in depression is thought to be a
factor associated with bad prognosis and worse disease course. IL-6 may directly
affect brain functioning and production of neurotransmitters; moreover, its
concentration is correlated with certain clinical symptoms within the wide range
of depressive symptomatology. Furthermore, there is a strong correlation between
IL-6 synthesis and psychosomatic functioning of the patient. This article
discusses potential sources and significance of IL-6 in the pathogenesis of
depression.
PMID- 28418767
TI - Randomized Controlled Trial of Survivorship Care Plans Among Low-Income,
Predominantly Latina Breast Cancer Survivors.
AB - Purpose The purpose of this study was to examine the effects of a randomized
controlled trial (RCT) of treatment summaries and survivorship care plans coupled
with a nurse counseling session, primarily on physician implementation of and
secondarily on patient adherence to recommended survivorship care, among a low
income population of breast cancer survivors (survivors). Methods We recruited
212 low-income, predominantly Latina (72.6%) survivors with stage 0 to III breast
cancer, with an average age of 53 years, from two Los Angeles County public
hospitals into an RCT of a survivorship care nurse counseling session coupled
with the provision of individualized treatment summaries and survivorship care
plans to patients and their health care providers from December 2012 to July
2014. One hundred seven survivors received the experimental intervention, and 105
survivors received usual care. Multiple linear regression analyses were performed
to assess intervention effects on physician implementation of and patient
adherence to recommended survivorship care. Scales that served as covariables
were Knowledge of Survivorship Issues, Perceived Efficacy in Patient-Physician
Interactions, and Satisfaction With Care and Information. Results Survivors in
the intervention group reported greater physician implementation of recommended
breast cancer survivorship care, for example, treatment of depression or hot
flashes, than did those in the control group (adjusted difference, 16 +/- 5.3; P
= .003). Baseline Satisfaction With Care and Information was positively
associated with physician implementation (coefficient, 5.2 +/- 2.2; P = .02).
Being married/partnered (-11.8 +/- 4.0; P = .004) and age (-0.5 +/- 0.2; P =
.028) were negatively associated with patient adherence. Conclusion To our
knowledge, this is the first RCT of survivorship care plans to show benefits in
clinical outcomes, in this case, showing increased physician implementation of
recommended breast cancer survivorship care in the intervention group, compared
with the control group.
PMID- 28418768
TI - Lipid biosynthesis: When the cell cycle meets protein synthesis?
PMID- 28418769
TI - Persistency of Neutralizing Anti-Interferon-beta Antibodies in Patients with
Multiple Sclerosis Treated with Subcutaneous Interferon-beta Depends on Antibody
Titers, IgG Subclasses, and Affinity Maturation.
AB - Neutralizing antibodies may affect interferon (IFN)-beta treatment efficacy, but
mechanisms of neutralizing anti-drug antibody (ADA) evolution are not fully
elucidated. We investigated the relationship between ADA titers, IgG subclass
profile, and binding affinity with the development and persistency of
neutralizing ADA in relapsing-remitting multiple sclerosis (MS) patients treated
with subcutaneous IFN-beta. A total of 94 patients, who had blood sampling at
months 6, 12, 24, and 36 during IFN-beta therapy, were included into this
retrospective study and stratified to the following: non-neutralizing, transient,
and persistent neutralizing ADA status. Patients without or with transient
neutralizing ADA displayed predominantly IgG1 and IgG3 subclasses, lower ADA
titers, and antibody binding affinity compared with patients having persistent
neutralizing ADA, in whom the predominant IgG subclasses were IgG2 and IgG4.
Overall, ADA binding affinity positively correlated with IgG4 and neutralizing
ADA titers, but negatively with IgG3 titers. Persistency of neutralizing ADA was
predicted by their titers at month 24 and month 36 of treatment and by an
increase of antibody affinity within the second year of IFN-beta treatment. The
humoral immune response to IFN-beta observed in MS patients as a result of IFN
beta therapy is a multifactorial process that is influenced by ADA titers,
affinity maturation, and IgG subclass switching.
PMID- 28418770
TI - Gene Silencing Activity and Hepatic Accumulation of Antisense Oligonucleotides
Bearing Cholesterol-Conjugated Thiono Triester at the Gap Region.
AB - Cholesterol (Chol) conjugation to the 5' or 3' end of antisense oligonucleotide
(ASO) enables delivery to the liver, and Chol conjugation at the gap region can
also be expected to improve delivery to the liver. In this study, we synthesized
ASOs bearing the Chol-conjugated thiono triester and evaluated their activity and
hepatic accumulation. We found that Chol conjugations at the gap region improved
in vitro activity and hepatic accumulation when compared to unconjugated ASOs.
However, Chol conjugation with phosphorothioate linkage did not improve in vivo
activity in the liver, suggesting the importance of cleaving the phosphodiester
between ASO and Chol. These results offer useful information for tuning the
oligonucleotide structure to improve pharmaceutical properties and designing ASOs
for multiple ligand conjugations and combinations with end modification.
PMID- 28418772
TI - Geographical Clusters and Predictors of Rabies in Three Southeastern States.
AB - The rabies virus causes progressive encephalomyelitis that is fatal in nearly
100% of untreated cases. In the United States, wildlife act as the primary
reservoir for rabies; prevention, surveillance, and control costs remain high.
The purpose of this study is to understand the current distribution of wildlife
rabies in three southeastern states, with particular focus on raccoons as the
primary eastern reservoir, as well as identify demographic and geographic factors
which may affect the risk of human exposure. This ecologic study obtained county
level rabies surveillance data from state health departments and the United
States Department of Agriculture Wildlife services for North Carolina, Virginia,
and West Virginia from 2010 to 2013. A spatial statistical analysis was performed
to identify county clusters with high or low rates of raccoon rabies in the three
states. Potential demographic and geographic factors associated with these
varying rates of rabies were assessed using a multivariable negative binomial
regression model. In North Carolina, raccoons constituted 50% of positive tests,
in Virginia, 49%, and in West Virginia, 50%. Compared to persons residing in West
Virginia counties, persons in North Carolina counties had 1.67 times the risk of
exposure (p < 0.0001) to a rabid raccoon and those in Virginia counties had 1.82
times the risk of exposure (p < 0.0001) to a rabid raccoon. Compared to those
counties where farmland makes up less than 17% of the total area, persons
residing in counties with 17-28% farmland had a 32% increased risk of exposure to
a rabid raccoon. In counties with 28-39% farmland, there was an 84% increased
risk of exposure. State, rurality, and percent of area designated as farmland
were the best predictors of risk of raccoon rabies exposure. Further research is
needed to better understand the effect of the oral rabies vaccine program in
controlling the risk of human exposure to raccoon rabies.
PMID- 28418773
TI - Willingness to Use Mobile Health in Glaucoma Patients.
AB - INTRODUCTION: Development of mobile health (m-health) in China carries tremendous
potential, especially for glaucoma, one of the major chronic ophthalmic diseases
afflicting millions of people. However, little research has been undertaken to
investigate the willingness of glaucoma patients to use m-health and the factors
influencing their decisions. SUBJECTS AND METHODS: This was a cross-sectional
study. A self-administered or face-to-face interview survey was performed on
1,487 patients with glaucoma at the outpatient glaucoma service, Zhongshan
Ophthalmic Center, Sun Yat-sen University. Questionnaires captured patients'
demographic data, WeChat access, and willingness to receive m-health. The data
were analyzed by single factor chi-square test. Multiple logistic regression
revealed the motivators and barriers to accept m-health adoption. RESULTS: One
thousand ninety-seven valid questionnaires were obtained. Seven hundred twenty
five respondents (66.1%) were willing to participate in m-health programs. 65.4%
were younger than 60 years old. 40.9% had travel time from home to hospital of >3
h. 63.6% had more than four follow-up visits for glaucoma. 86.5% experienced
trouble events during clinic visits. The overall WeChat usage rate was 61.7%.
Age, travel time, number of visits, trouble events in clinic, and WeChat access
in patients with glaucoma were related to the willingness to use m-health (p <
0.05). CONCLUSIONS: Most patients with glaucoma were willing to participate in m
health programs, which are essential to increasing and improving access to care.
PMID- 28418771
TI - Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory
CD8+ T Cells.
AB - Respiratory virus infections, such as those mediated by influenza virus,
parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory
syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for
substantial morbidity and mortality, especially in children and older adults.
Furthermore, the potential emergence of highly pathogenic strains of influenza
virus poses a significant public health threat. Thus, the development of vaccines
capable of eliciting long-lasting protective immunity to those pathogens is a
major public health priority. CD8+ Tissue-resident memory T (TRM) cells are a
newly defined population that resides permanently in the nonlymphoid tissues
including the lung. These cells are capable of providing local protection
immediately after infection, thereby promoting rapid host recovery. Recent
studies have offered new insights into the anatomical niches that harbor lung
CD8+ TRM cells, and also identified the requirement and limitations of TRM
maintenance. However, it remains controversial whether lung CD8+ TRM cells are
continuously replenished by new cells from the circulation or permanently lodged
in this site. A better understanding of how lung CD8+ TRM cells are generated and
maintained and the tissue-specific factors that drive local TRM formation is
required for optimal vaccine development. This review focuses on recent advance
in our understanding of CD8+ TRM cell establishment and maintenance in the lung,
and describes how those processes are uniquely regulated in this tissue.
PMID- 28418774
TI - Arsenic in the groundwater: Occurrence, toxicological activities, and remedies.
AB - Arsenic (As) contamination in groundwater has become a geo-environmental as well
as a toxicological problem across the globe affecting more than 100-million
people in nearly 21 countries with its associated disease "arsenicosis." Arsenic
poisoning may lead to fatal skin and internal cancers. In present review, an
attempt has been made to generate awareness among the readers about various
sources of occurrence of arsenic, its geochemistry and speciation, mobilization,
metabolism, genotoxicity, and toxicological exposure on humans. The article also
emphasizes the possible remedies for combating the problem. The knowledge of
these facts may help to work on some workable remedial measure.
PMID- 28418775
TI - Research 101: An Initiative to Encourage and Facilitate Quality Resident Research
in a Military Setting.
AB - Objective Describe and evaluate a structured research program initiated at a
tertiary Department of Defense (DOD) Medical Training Facility (MTF) to encourage
and facilitate the conduct of research investigations, specifically among
residents and junior or inexperienced investigators, but applicable for all DOD
otolaryngology (ENT) and audiology providers. Methods A new comprehensive program
was deployed in the ENT clinic at Madigan Army Medical Center (MAMC) to help
improve the research program. Identified gaps in research methods and regulatory
training were incorporated into the existing graduate medical education program
along with structured mentorship between residents and senior staff. Academic
achievements (eg, research protocols, publications, presentations at
national/international meetings, and funding) for the ENT clinic were examined
from 1992 to 2016, and changes in academic achievements were analyzed for
success. Results The implementation of a structured research curriculum improved
the number of protocols submitted and the quality of research being accepted for
publication (ie, journal impact factor). Funding for research increased
significantly to represent a third of the total research portfolio for the entire
hospital. Discussion The benefit of employing a research specialist to oversee
the resident research experience can greatly influence the quantity and quality
of a resident program's research portfolio. Implications for Practice Improving
resident research activity can potentially advance the quality of the resident
program, help with evidence-based medical approaches, and increase residents'
chances of matching for fellowship.
PMID- 28418776
TI - 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic
metabolites of pyrrolizidine alkaloids.
AB - Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic
phytochemicals. Metabolism of PAs in vivo generates four (+/-)-6,7-dihydro-7
hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed
to be responsible for PA-induced liver tumor formation in rats. In this present
study, we determined that the same set of DHP-DNA adducts was formed upon the
incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human
hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7
cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to
form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor
formation.
PMID- 28418777
TI - ER/LA opioid REMS and accredited education: Survey results provide insight into
clinical roles, educational needs, and learner preferences.
AB - BACKGROUND: The Collaborative for REMS (Risk Evaluation and Mitigation Strategy)
Education (CO*RE) includes 13 organizations that provide REMS Program Companies
(RPC) grant-supported accredited education on extended-release and long-acting
(ER/LA) opioid therapy. This report summarizes results of a survey designed to
investigate the impact of participant criteria and to better understand the roles
and preferences of continuing medical education/continuing education (CME/CE)
participants. METHODS: In April 2015, the authors made an online survey available
to an estimated 10,000 clinicians who had completed a CO*RE CME/CE activity since
2013. The purpose of the survey was to (1) examine possible reasons learners may
underreport prescribing status, (2) investigate ways in which learners engage in
nonprescribing roles relevant to reducing adverse patient outcomes, and (3)
determine the acceptability of a potential test-based learning tool that allows
participants with mastery to test out in lieu of participating in 2- to 3-hour
education. RESULTS: Findings revealed that there was little confusion or
reluctance by learners to answer questions about Drug Enforcement Administration
(DEA) licensing and whether they prescribed opioids in the past year. REMS
"prescriber" education covers opioid management responsibilities that are
distributed among team members who play critical nonprescribing roles in reducing
serious adverse outcomes from both ER/LA and immediate-release (IR) opioids.
Seventy-three percent of study participants would favor a test-based learning
tool should future circumstances warrant it. CONCLUSION: The authors concluded
the likelihood of underreporting is small, but there is an opportunity to clarify
license and prescribing questions; opioid management responsibilities are
distributed among nonprescribing team members who play roles in reducing adverse
outcomes from both ER/LA and IR opioids, who would therefore benefit from REMS
education; and clinicians favor a test-based learning tool, should future
circumstances warrant it. These findings could have implications for planning
future ER/LA opioid REMS curriculum and for setting and interpreting training
goals for the US Food and Drug Administration's (FDA) ER/LA opioid REMS program.
PMID- 28418778
TI - Parkinsonism Signs and Symptoms in Agricultural Pesticide Handlers in Washington
State.
AB - OBJECTIVES: Examine associations between pesticide exposure and signs or symptoms
of parkinsonism. METHODS: Prior to the 2014 pesticide spray season, the authors
examined 38 active pesticide handlers aged 35 to 65 (median: 43.5) who
participated in the State of Washington's cholinesterase monitoring program in
the Yakima Valley, where cholinesterase-inhibiting insecticides are applied in
fruit orchards. A movement disorder specialist assessed the workers using the
Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore 3 (UPDRS3).
Participants also self-reported work and medical histories, including the UPDRS
activities of daily living subscore 2 (UPDRS2). The authors explored the relation
between these scores and lifetime occupational pesticide exposure while
accounting for age. RESULTS: All participants were Hispanic men born in Mexico
who had worked in agriculture for 4 to 43 years (median: 21 years, including 11
years applying pesticides, mostly in the United States). Ten participants (26%)
reported difficulty with one or more UPDRS2 activities of daily living (maximum =
2), and nine (24%) had a UPDRS3 >0 (maximum = 10). The most common symptom and
sign, respectively, were excess saliva (n = 6) and action tremor (n = 5). UPDRS2
and UPDRS3 scores were unrelated to the number of years applying pesticides, but
UPDRS3, especially action tremor, was positively associated with living on or by
a farm. CONCLUSIONS: Symptoms and signs of parkinsonism were absent to mild in
this small sample of active workers who apply cholinesterase-inhibiting
insecticides in Washington State, USA. Future studies should be larger and
examine older, retired workers with greater cumulative exposure to agricultural
pesticides at work and home, including other types of agricultural pesticides.
PMID- 28418779
TI - Determining a Successful Nasal Airway Surgery: Calculation of the Patient
Centered Minimum Important Difference.
AB - Objective Determine whether the patient-identified minimum important difference
(MID) in Nasal Obstruction Symptom Evaluation (NOSE) score differs from a
statistically calculated estimate of MID in patients with septal deviation
undergoing nasal airway surgery. Study Design Prospective cohort. Setting
Tertiary academic referral center. Subjects Patients with nasal obstruction due
to septal deviation. Methods Patients completed the NOSE questionnaire
preoperatively and indicated the change from their baseline score that they would
consider the minimum improvement required to define the septoplasty with
turbinate reduction as successful. A previously published distribution-based
approach was used to estimate the MID based on baseline NOSE scores. Scores were
reported both as a raw score and as a percentage of patients' baseline scores.
One-sample t test was used to compare the statistically estimated MID to the
patient-reported MID. Results Seventy-six patients were included. The mean (SD)
baseline NOSE score was 12.9 (4.03). The mean (SD) patient-identified MID was 5.3
(2.1), corresponding to a 41.1% change (95% confidence interval, 37.2-41.3) from
baseline. The statistically estimated MID was 5.2 points (40.3% reduction from
baseline scores). The estimated MID was not significantly different from the
patient-identified MID ( P = .4). Conclusion In patients with septal deviation,
an improvement of approximately 40% in their nasal obstructive symptoms as
assessed by the NOSE questionnaire is required to define a nasal airway surgery
as successful. The patient-identified and the statistically calculated MIDs were
similar. Furthermore, this MID can be used to guide research, improving the
ability to use the NOSE score as a dichotomous scoring measure (treatment
success/failure) and estimating sample size.
PMID- 28418780
TI - Unique phylogenetic position of the African truffle-like fungus, Octaviania
ivoryana (Boletaceae, Boletales), and the proposal of a new genus,
Afrocastellanoa.
AB - The sequestrate (truffle-like) basidiomycete Octaviania ivoryana was originally
described based on collections from Zimbabwe, Kenya, Guinea, and Senegal. This
species has basidiomes that stain blue-green and basidiospores with crowded
spines that are characteristic of the genus Octaviania. However, O. ivoryana is
the only Octaviania species described from sub-Saharan Africa, and the
phylogenetic relationship of the species to other species of Octaviania sensu
stricto has not been previously investigated. We examined the phylogenetic
position of the isotype and paratype specimens of O. ivoryana based on two nuc
rDNA loci-ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]) and partial 28S-and
the translation elongation factor 1-alpha gene. The resultant phylogenies
indicate that O. ivoryana does not belong to Octaviania s. s. but instead forms a
clade with the epigeous bolete genus, Porphyrellus sensu stricto (i.e., P.
porphyrosporus and allies). The internal transcribed spacer phylogeny also
recovers a monophyletic clade that includes sequences from O. ivoryana basidiomes
as well as sequences from ectomycorrhizal root tips of Uapaca, Anthonotha, and
assorted ectomycorrhizal Fabaceae species, suggesting that there is likely
additional undescribed diversity within the lineage. We accordingly propose a new
genus, Afrocastellanoa M.E. Sm. & Orihara, to accommodate the species O.
ivoryana. Afrocastellanoa is morphologically distinct from Octaviania in the
combination of a solid gleba, multilayered peridium, and the lack of distinct
hymenium within the gleba. Our data suggest that the genus Afrocastellanoa is a
unique sequestrate lineage with one described species and several undescribed
species, all of which likely form ectomycorrhizas with African trees.
PMID- 28418781
TI - Induction Chemotherapy plus Concurrent Chemoradiotherapy vs Concurrent
Chemoradiotherapy in Elderly Patients with Advanced Nasopharyngeal Carcinoma.
AB - Objective This study aimed to compare survival and toxicity between induction
chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) and concurrent
chemoradiotherapy (CCRT) alone in elderly patients with advanced nasopharyngeal
carcinoma (NPC). Study Design Propensity-matched analysis of survival and
toxicity in a retrospective elderly cohort. Setting Department of Medical
Oncology, Jingzhou Hospital, Tongji Medical College, Huazhong University of
Science and Technology, China. Subjects and Methods In total, 193 patients with
stage III to IVb NPC who were treated with IC + CCRT or CCRT alone were enrolled.
A cohort with suitable propensity scores was created (82 patients in the IC +
CCRT group and 82 patients in the CCRT group). Survival and toxicity were
compared between the 2 groups. Results For the IC + CCRT group and the CCRT
group, the 5-year locoregional failure-free survival (LRFFS) rate was 80.4% and
77.2% ( P = .53), the 5-year distant failure-free survival (DFFS) rate was 80%
and 76.9% ( P = .517), the 5-year overall survival (OS) rate was 71.8% and 60.5%
( P = .26), and the 5-year cancer-specific survival (CSS) rate was 75.3% and
66.7% ( P = .144), respectively. There was a significant difference in the
cumulative incidence of all grade 3 to 4 toxicities between the 2 groups (29.9%
vs 17.7%, P = 4.8 * 10-6). Conclusions IC + CCRT had a high cumulative incidence
of grade 3 to 4 toxicities in elderly patients with advanced NPC, while there
were no improvements in 5-year LRFFS rate, DFFS rate, OS rate, or CSS rate
between patients who underwent the IC + CCRT vs CCRT alone. Concurrent
chemoradiotherapy alone is still the standard of treatment.
PMID- 28418782
TI - Knockdown of IL-8 Provoked Premature Senescence of Placenta-Derived Mesenchymal
Stem Cells.
AB - Mesenchymal stem cells (MSCs) have shown promise for use in cell therapy, and due
to their tumor tropism can serve as vehicles for delivering therapeutic agents to
tumor sites. Because interleukin-8 (IL-8) is known to mediate the protumor effect
of MSCs, elimination of IL-8 secretion by MSCs may enhance their safety for use
in cancer gene therapy. However, little is known concerning the effect of
endogenously secreted IL-8 on MSCs. We performed studies using placenta-derived
MSCs (PMSCs) to determine whether knockdown of IL-8 would influence their
biological activity. We first verified that IL-8 and its membrane receptor CXCR2,
but not CXCR1, were highly expressed in PMSCs. We then employed lentivirus
mediated small hairpin RNA interference to generate stable IL-8-silenced PMSCs,
which displayed a variety of characteristic senescent phenotypes. We observed
that at day 9 post-transfection, IL-8-silenced PMSCs had become larger and
displayed a more flattened appearance when compared with their controls.
Moreover, their proliferation, colony forming unit-fibroblast formation,
adipogenic and osteogenic differentiation, and immunosuppressive potentials were
significantly impaired. Enhanced senescence-associated beta-galactosidase (SA
beta-gal) activity and specific global gene expression profiles confirmed that IL
8 silencing evoked the senescence process in PMSCs. Increased levels of p-Akt and
decreased levels of FOXO3a protein expression suggested that reactive oxygen
species played a role in the initiation and maintenance of senescence in IL-8
silenced PMSCs. Notably, the majority of CXCR2 ligands were downregulated in
presenescent IL-8-silenced PMSCs but upregulated in senescent cells, indicating
an antagonistic pleiotropy of the IL-8/CXCR2 signaling pathway in PMSCs. This
effect may promote the proliferation of young cells and accelerate senescence of
old cells.
PMID- 28418783
TI - Locoregional Flaps for Oral Cavity Reconstruction: A Review of Modern Options.
AB - Objective To review state-of-the-art modifications and advances in soft tissue
local and regional flap reconstruction of the oral cavity and to determine the
role these techniques play in current practice. Data Sources Review of the
literature regarding oral cavity reconstruction. Review Methods The authors
describe advances in locoregional reconstructive options and assimilate data from
the literature that compare recent advances to the historic standards.
Conclusions Modern advances in regional reconstruction of the oral cavity offer
outstanding results and demonstrate potential advance over free tissue transfer.
These modifications demonstrate the prominent role that regional reconstruction
can play in oral cavity reconstruction. Implications for Practice With a more
complete understanding of these options, the surgeon is better able to tailor the
reconstruction to the needs of the patient to provide high-quality cost-effective
care.
PMID- 28418784
TI - A Fresh Cadaver Model for the Instruction of Ultrasound-Guided Fine-Needle
Aspiration of Thyroid Nodules.
AB - Objective The aim of our study is to determine if a fresh cadaver model (FCM) for
the instruction of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid
nodules is a practical method for instruction. Study Design Pre- and
postinstruction assessment of medical students' ability to perform US-guided FNA
of artificially created thyroid nodules placed adjacent to the thyroid gland of a
fresh cadaver. Setting University-based fresh cadaver laboratory. Subjects and
Methods Study participants included a total of 17 first- and second-year medical
students with minimal US training. Technical skills were assessed using a 10-item
checklist. In addition, a cognitive assessment regarding the indications,
contraindications, and complications of the procedure was completed. A
postinstruction assessment was provided for participants 5 weeks after their
initial assessment. Differences between pre- and postinstruction assessment
scores of technical skills were analyzed using McNemar's test. The mean cognitive
knowledge gain was analyzed using a paired 2-sample t test. Results Eight of 10
items on the skills checklist were statistically significant between pre- and
postinstruction skills assessment ( P < .05). There was a statistically
significant change in cognitive knowledge gain regarding the contraindications of
the procedure ( P = .001), but not for indications or complications ( P = .104
and P = .111, respectively). Conclusion US-guided FNA continues to be an
important diagnostic procedure in the workup of thyroid nodules, making it an
essential skill to integrate into surgical skills lab. Our FCM for the
instruction of US-guided FNA is the first of its kind, and this pilot study shows
this is a viable method for instruction.
PMID- 28418785
TI - Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood
Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents.
AB - Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs
(UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue
regeneration because of their higher proliferation potential, lack of donor site
morbidity, and their off-the-shelf potential. MSCs differentiated toward the
osteogenic lineage exhibit a specific metabolic phenotype characterized by
reliance to oxidative phosphorylation for energy production and reduced
glycolytic rates. Currently, limited information exists on the metabolic
transitions at different stages of the osteogenic process after osteoinduction
with different agents. Herein, the osteoinduction efficiency of BMP-2 and
dexamethasone on UCB MSCs was assessed using gas chromatography-mass spectrometry
(GC-MS) metabolomics analysis, revealing metabolic discrepancies at 7, 14, and 21
days of induction. Whereas both agents when administered individually were able
to induce collagen I, osteocalcin, and osteonectin expression, BMP-2 was less
effective than dexamethasone in promoting alkaline phosphatase expression. The
metabolomics analysis revealed that each agent induced distinct metabolic
alterations, including changes in amino acid pools, glutaminolysis, one-carbon
metabolism, glycolysis, and tricarboxylic acid cycle. Importantly, we showed that
in vitro-differentiated UCB MSCs acquire a metabolic physiology similar to
primary osteoblasts when induced with dexamethasone but not with BMP-2,
highlighting the fact that metabolomics analysis is sensitive enough to reveal
potential differences in the osteogenic efficiency and can be used as a quality
control assay for evaluating the osteogenic process.
PMID- 28418786
TI - Evaluation in Mice of the Immunogenicity of a Tetravalent Subunit Vaccine
Candidate Against Dengue Virus Using Mucosal and Parenteral Immunization Routes.
AB - Our group has developed a subunit vaccine candidate against Dengue virus (DENV)
based on two different viral regions, the domain III of the envelope protein and
the capsid protein. The chimeric proteins for each serotype (DIIIC1-4),
aggregated with the oligodeoxynucleotide 39 M, form the tetravalent formulation
named Tetra DIIIC. Tetra DIIIC induces a protective immune response in mice when
it is inoculated by intraperitoneal route. However, if children are the main
targets for a DENV vaccine, then a needle-free route of administration should be
attractive and advantageous. In this study, we evaluated for the first time, in
vivo, a vaccine candidate against DENV based on recombinant proteins using the
intranasal route. After three doses of Tetra DIIIC in mice, we measured the
humoral immune response against the four DENV serotypes and the corresponding
recombinant proteins. Moreover, the functionality of these antibodies was
evaluated through a plaque reduction neutralization test. Finally, to assess the
cellular immune response induced, we measured the IFN-gamma-levels secreted by
spleen cells after in vitro stimulation with DENV. The results presented in this
study indicate that the intranasal immunization with Tetra DIIIC favors the
generation of DENV-specific cell-mediated immunity. On the other hand, the
immunization using intraperitoneal and intranasal routes, simultaneously,
generate functional antibodies (anti-DIIIC and anti-DENV) and an in vitro
response of IFN-gamma secretion.
PMID- 28418787
TI - Lulworthia atlantica: a new species supported by molecular phylogeny and
morphological analysis.
AB - This study presents morphological and molecular evidence for the establishment of
a new species of Lulworthia based on the evaluation of 11 isolates of
Lulworthiales collected in two marinas on the west coast of Portugal initially
classified as Lulworthia sp. Maximum likelihood and Bayesian methods were applied
to obtain phylogenetic trees for 18S-28S and internal transcribed spacer (ITS1
5.8S-ITS2 = internal transcribed spacer [ITS]) nuc rDNA. The isolates
consistently grouped together in a distinct and highly supported clade; all other
Lulworthiales analyzed, including the available sequences of Lulworthia spp.,
segregated separately. These results were supported by common and distinctive
morphological characters and enabled recognition and description of the new
species Lulworthia atlantica. Two Portuguese isolates were confirmed as
Lulworthia cf. purpurea, and two were confirmed as asexual morphs of Zalerion
maritima.
PMID- 28418788
TI - Factors Associated with Delayed Cooling in Cardiac Arrest Patients.
AB - Therapeutic hypothermia has been shown to improve neurologic outcome in medical
cardiac arrest patients, yet little is known about factors that delay target
temperature achievement. Our primary aim was to identify factors associated with
not achieving our institutional "door-to-cool" (DTC) performance goal (emergency
department [ED] arrival to temperature of 34 degrees C) of <=4 hours. Secondary
aims included whether achievement of DTC goal was associated with timing of bolus
neuromuscular blockade (NMB), survival, or functional outcome. This was a
retrospective cohort study of a medical cardiac arrest quality improvement (QI)
database that included patients treated from November 2007 to August 2012. The
database was queried for patient demographics, arrest characteristics, specific
cooling techniques used, whether patients underwent emergent computed tomography
imaging or cardiac catheterization, and patient outcomes. Logistic regression was
used to assess the factors associated with DTC goal performance and outcomes. We
enrolled 327 patients, median age 58, median return of spontaneous circulation
(ROSC) time of 21 minutes (interquartile range [IQR] 14-29 minutes), and
shockable initial rhythm in 61%. One hundred forty-four (44%) patients survived
to hospital discharge, 133 (41%) with good functional outcome, as defined as
cerebral performance category 1-2. Induction with cold IV fluids [OR 0.50 (CI:
0.29-0.85)] and NMB administration within 2 hours of ED arrival [OR 2.95 (CI:
1.17-7.43)] was associated with achieving DTC goal. Logistic regression showed
that achievement of DTC goal <=4 hours [OR 0.59 (0.32-1.09)] was not associated
with good functional outcome. In our single-center cohort, initiation of cold
intravenous fluids (IVF) and early NMB administration were associated with
improved DTC goal performance of 4 hours. However, patients achieving DTC goals
were not associated with improved outcomes.
PMID- 28418790
TI - Distortion-product otoacoustic emissions in workers exposed to urban stressors.
AB - The study aimed to compare the distortion-product otoacoustic emissions (DPOAEs)
with the pure-tone audiometry and to analyze the changes in participants exposed
to noise. The results show a prevalence of participants with impaired DPOAEs
higher than the prevalence of participants with impaired audiometries in the
total sample, in men, and in outdoor workers and a prevalence of impaired DPOAEs
and of impaired audiometries in men higher than in women and in outdoor workers
higher than in indoor workers. The comparison of mean values between outdoor and
indoor workers shows a significant difference only on some frequencies, in the DP
gram. The results suggest a higher effectiveness of DPOAEs compared with the pure
tone audiometry in identifying the presence of any damage in individuals exposed
to noise at an early stage.
PMID- 28418789
TI - Transitions and Motivations for Substance Misuse in Prison Inmates With ADHD and
Conduct Disorder: Validation of a New Instrument.
AB - OBJECTIVE: There is a reasonable theoretical base for understanding the possible
causes and motivations behind substance misuse and its dependency. There is a
need for a reliable and valid measure that delineates the markers of substance
use from its initiation and identifies different motivations for drug use
transitioning, maintenance, and dependency. We addressed this gap in the United
Kingdom by examining and validating the Substance Transitions in Addiction Rating
Scale (STARS). METHODS: For this review, 390 male prisoners were screened for
conduct disorder and assessed with a clinical diagnostic interview for attention
deficit/hyperactivity disorder (ADHD). They completed the four STARS subscales
regarding their substance use. Exploratory structural equation modeling was
performed to assess the STARS structure and to derive factors to assess validity
against ADHD and conduct disorder diagnostic categories. RESULTS: Each of the
subscales produced meaningful and reliable factors that supported the self
medication and behavioral disinhibition hypotheses of substance use motivation.
The findings robustly show that ADHD is significantly associated with the need
for coping as a way of managing primary and comorbid symptoms, but not conduct
disorder. The findings were strongest for the combined ADHD type. DISCUSSION:
STARS has a great potential to further the understanding of the motivation behind
substance use and its dependency in different populations.
PMID- 28418792
TI - JHL News.
PMID- 28418791
TI - Superior Semicircular Canal Dehiscence Symptoms Unmasked by Ossicular Chain
Reconstruction.
PMID- 28418793
TI - Wide Variability in Caloric Density of Expressed Human Milk Can Lead to Major
Underestimation or Overestimation of Nutrient Content.
AB - BACKGROUND: Very-low-birth-weight infants continue to face significant
difficulties with postnatal growth. Human milk is the optimal form of nutrition
for infants but may exhibit variation in nutrient content. OBJECTIVE: This study
aimed to perform macronutrient analysis on expressed human milk from mothers
whose babies are hospitalized in the neonatal intensive care unit. METHODS: Up to
five human milk samples per participant were analyzed for protein, carbohydrate,
and fat content using reference chemical analyses (Kjeldahl for protein, high
pressure liquid chromatography for carbohydrates, and Mojonnier for fat). Calorie
content was calculated. RESULTS: A total of 64 samples from 24 participants was
analyzed. Wide variability was found in calorie, protein, carbohydrate, and fat
composition. The authors found an average of 17.9 kcal/ounce, with only 34% of
samples falling within 10% of the expected caloric density. CONCLUSION: The
assumption that human milk contains 20 kcal/ounce is no longer supported based on
this study. This supports promoting an individualized nutrition strategy as a
crucial aspect to optimal nutrition.
PMID- 28418795
TI - Examining Racial Disparities in Breastfeeding From a Positive Deviance Lens: A
Commentary.
PMID- 28418796
TI - Considering Inequities in Breastfeeding.
PMID- 28418794
TI - Microbial Diversity in Milk of Women With Mastitis: Potential Role of Coagulase
Negative Staphylococci, Viridans Group Streptococci, and Corynebacteria.
AB - BACKGROUND: Lactational mastitis constitutes a significant cause of premature
weaning. However, its etiology, linked to the presence of pathogenic
microorganisms, has been scarcely reported. Research aim: The aim of this study
was to describe the microbial diversity in milk samples from women suffering from
lactational mastitis and to identify more accurately a collection of isolates
belonging to coagulase-negative staphylococci, streptococci, and coryneform
bacteria. METHODS: This is a cross-sectional descriptive one-group study. A total
of 5,009 isolates from 1,849 mastitis milk samples was identified by culture,
biochemical, and/or molecular methods at the species or genus level. A more
precise identification of a collection of 211 isolates was carried out by 16S
rRNA gene sequencing. RESULTS: Mean total bacterial count in milk samples was
4.11 log10 colony-forming units/ml, 95% confidence interval [4.08, 4.15].
Staphylococcus epidermidis was the most common species being isolated from 91.56%
of the samples, whereas Staphylococcus aureus was detected in 29.74%.
Streptococci and corynebacteria constituted the second (70.20%) and third
(16.60%) most prevalent bacterial groups, respectively, found in this study. In
contrast, Candida spp. was present in only 0.54% of the samples. Sequencing of
the 16S rRNA gene revealed a high diversity of bacterial species among identified
isolates. CONCLUSION: Many coagulase-negative staphylococci, viridans group
streptococci, and corynebacteria, usually dismissed as contaminant bacteria, may
play an important role as etiologic agents of mastitis. Proper diagnosis of
mastitis should be established after performing microbiological testing of milk
based on standardized procedures. A reliable analysis must identify the mastitis
causing pathogen(s) at the species level and its(their) concentration(s).
PMID- 28418797
TI - Reframing the Context of the Breastfeeding Narrative: A Critical Opportunity for
Health Equity Through Evidence-Based Advocacy.
PMID- 28418799
TI - Association News From the ILCA Board of Directors.
PMID- 28418798
TI - Evidence of a Preventive Effect of Breastfeeding on Obstructive Sleep Apnea in
Children and Adults.
PMID- 28418800
TI - Predictors of Breastfeeding Initiation and Maintenance in an Integrated
Healthcare Setting.
AB - BACKGROUND: The American Academy of Pediatrics recommends exclusive breastfeeding
to age 6 months. Although breastfeeding rates in the United States have been
increasing over time, further improvements are needed to meet Healthy People 2020
targets. Research aim: This study examined predictors of breastfeeding initiation
and maintenance among a population of insured pregnant women. METHODS:
Participants were 1,149 pregnant women enrolled in the Pregnancy and Influenza
Project in two Kaiser Permanente regions in 2010-2011. Data were collected
through interviews at enrollment and 1 month and 6 months postpartum and through
participants' electronic medical records. RESULTS: Nearly all (99%) women
reported initiating breastfeeding. Rates of exclusive breastfeeding were 70% and
54% at 1 month and 6 months, respectively; an additional 22% and 23% of women
reported supplementing breastfeeding with formula. Of the women who supplemented,
the mean ( SD) infant age at formula introduction was 53 (62) days. Of those who
had stopped breastfeeding, the mean ( SD) infant age at cessation was 85 (59)
days. Higher maternal education level, better maternal self-rated health,
prenatal folic acid use, absence of chronic medical conditions, and infant full
term birth were significantly associated with breastfeeding maintenance.
CONCLUSION: Although rates of breastfeeding in this population were higher than
national rates, a significant number of women stopped breastfeeding or introduced
formula earlier than recommended. Two to 3 months postpartum may be a critical
period warranting additional encouragement or intervention by healthcare
providers. Mothers' education attainment, maternal health factors, and
gestational age at delivery may predict likelihood of breastfeeding maintenance.
PMID- 28418801
TI - About Research: Qualitative Methodologies.
PMID- 28418802
TI - Transfer of Low Dose Aspirin Into Human Milk.
AB - BACKGROUND: Aspirin has antipyretic and anti-inflammatory properties and is
frequently used by pregnant and lactating women. However, its transfer in human
milk when administered at low dose has not been reported. Research aim: This
study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite,
salicylic acid, into human milk following the use of low dose aspirin. METHODS:
In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours
from seven breastfeeding women after a steady-state daily dose of 81 mg of
aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined
by liquid chromatography-tandem mass spectrometry. RESULTS: Acetylsalicylic acid
levels were below the limit of quantification (0.61 ng/ml) in all the milk
samples, whereas salicylic acid was detected at very low concentrations. The
average concentration of salicylic acid observed was 24 ng/ml and the estimated
relative infant dose was 0.4%. CONCLUSION: Acetylsalicylic acid transfer into
milk is so low that it is undetectable even by highly sophisticated methodology.
Salicylic acid does appear in the human milk in comparatively low amounts, which
are probably subclinical in infants. Thus, the daily use of an 81-mg dose of
aspirin should be considered safe during lactation.
PMID- 28418803
TI - An Ecological Momentary Assessment of Primiparous Women's Breastfeeding Behavior
and Problems From Birth to 8 Weeks.
AB - BACKGROUND: Primiparous women are at risk for early, unintended breastfeeding
reduction and cessation. Breastfeeding patterns that contribute to these outcomes
require further exploration. Research aim: This study aimed to describe early,
"real-time" breastfeeding behaviors and perceived problems of primiparous women.
METHODS: First-time mothers intending to exclusively breastfeed downloaded a
commercial infant-feeding app during their postpartum hospitalization. Women
logged feedings and their breastfeeding experiences, as they occurred, through 8
weeks postpartum. Additional feeding and background data were collected via
electronic medical records and questionnaires administered at enrollment and 2
and 8 weeks postpartum. Summary statistics were compiled to examine weekly
breastfeeding behaviors and problems. RESULTS: In this sample of 61 primarily
highly educated, White women committed to breastfeeding, 38% ( n = 23) used
formula during the postpartum hospitalization and 68% ( n = 34) used formula at
least once by 2 weeks. Nine women stopped breastfeeding during the study. Women
using any formula in the hospital and those with less positive baseline attitudes
toward breastfeeding were less likely to be exclusively breastfeeding at 2 and 8
weeks, respectively ( p < .05). There was a trend toward declining at-breast
feeds and high rates of milk expression during the study. Breastfeeding problems
peaked at Week 2, with 81% of women ( n = 39) endorsing at least one problem at
that time. The most prevalent problems included perception of inadequate milk,
pain, latching, and inefficient feeds. CONCLUSION: Interventions to address
suboptimal breastfeeding in primiparous women should consider the pervasiveness
of early milk expression and in-hospital formula supplementation in this
population, as well as the trajectory of common problems.
PMID- 28418804
TI - Determinants of Nonmedically Indicated In-Hospital Supplementation of Infants
Whose Birthing Parents Intended to Exclusively Breastfeed.
AB - BACKGROUND: Despite high rates of intention to exclusively breastfeed, rates of
exclusive breastfeeding in Canada are low. Supplementation may begin in hospital
and is associated with reduced breastfeeding duration. Research aim: The aim of
this investigation was to explore determinants of in-hospital nonmedically
indicated supplementation of infants whose birthing parents intended to
exclusively breastfeed. METHODS: This study is a cross-sectional one-group
nonexperimental design, focused on participants who intended to exclusively
breastfeed for 6 months ( n = 496). Data were collected between October 2011 and
October 2015 in Newfoundland and Labrador. Variables measured included age;
rural/urban location; education; income; race; marital status; parity; smoking
status; having been breastfed as an infant; previous breastfeeding experience;
Iowa Infant Feeding Attitude Scale score; delivery mode; infant birth weight;
birth satisfaction; skin-to-skin contact; length of participant's hospital stay;
breastfeeding advice from a lactation consultant, registered nurse, or physician;
and first impression of breastfeeding. We evaluated determinants of in-hospital
nonmedically indicated supplementation using bivariate and multivariate logistic
regression analyses. RESULTS: Overall, 16.9% ( n = 84) of infants received
nonmedically indicated supplementation in hospital. Multivariate modeling
revealed four determinants: low total prenatal Iowa Infant Feeding Attitude Scale
score (odds ratio [OR] = 1.96, 95% confidence interval [CI] [1.18, 3.27]), no
previous breastfeeding experience (OR = 2.03, 95% CI [1.15, 3.61]), negative
first impression of breastfeeding (OR = 2.67, 95% CI [1.61, 4.43]), and receiving
breastfeeding advice from a hospital physician (OR = 2.86, 95% CI [1.59, 5.15]).
CONCLUSION: Elements of the hospital experience, self-efficacy, and attitudes
toward infant feeding are determinants of nonmedically indicated supplementation
of infants whose birthing parents intended to exclusively breastfeed.
PMID- 28418805
TI - Public Attitudes Toward Breastfeeding in Public Places in Ottawa, Canada.
AB - BACKGROUND: In Ontario, Canada, breastfeeding in public is a protected right, yet
even with these laws, attitudes toward breastfeeding in public can serve as a
barrier to breastfeeding. Research aim: This study assesses public support for
breastfeeding in public among adults in Ottawa, Ontario, and examines
sociodemographic associations with negative attitudes toward public
breastfeeding. METHODS: Data from the 2015 Rapid Risk Factor Surveillance System
(RRFSS), a population health telephone survey, were obtained for Ottawa. Adults
ages 18 years and older were asked whether it was acceptable for a mother to
breastfeed her baby in a restaurant and shopping mall ( n = 1,276). Descriptive
statistics and regression were used to describe sociodemographic characteristics
associated with negative attitudes. RESULTS: Overall, 75% of respondents agreed
that it was acceptable for a mother to breastfeed her baby in both a restaurant
and shopping mall (restaurant: 78%; shopping mall: 81%). Respondents who did not
have children at home, were less educated, had a mother tongue language other
than French or English and who were retirees were less likely to support
breastfeeding in restaurants and shopping malls. In addition, women and
immigrants living in Canada for more than 15 years were less likely to support
breastfeeding in shopping malls. CONCLUSION: Despite a law to support public
breastfeeding in Ontario, there is room to improve attitudes toward public
breastfeeding. Increased public support for public breastfeeding can support
women and children to achieve their feeding goals, particularly for those wanting
to exclusively breastfeed.
PMID- 28418806
TI - Lactation Newsmakers: An Interview With Laurence Grummer-Strawn, MPA, MA, PhD.
PMID- 28418807
TI - Coagulase-Negative Staphylococci in Human Milk From Mothers of Preterm Compared
With Term Neonates.
AB - BACKGROUND: Human milk is the preferred nutrition for neonates and a source of
bacteria. Research aim: The authors aimed to characterize the molecular
epidemiology and genetic content of staphylococci in the human milk of mothers of
preterm and term neonates. METHODS: Staphylococci were isolated once per week in
the 1st month postpartum from the human milk of mothers of 20 healthy term and 49
preterm neonates hospitalized in the neonatal intensive care unit. Multilocus
variable-number tandem-repeats analysis and multilocus sequence typing were used.
The presence of the mecA gene, icaA gene of the ica-operon, IS 256, and ACME
genetic elements was determined by PCR. RESULTS: The human milk of mothers of
preterm compared with term neonates had higher counts of staphylococci but lower
species diversity. The human milk of mothers of preterm compared with term
neonates more often contained Staphylococcus epidermidis mecA (32.7% vs. 2.6%),
icaA (18.8% vs. 6%), IS 256 (7.9% vs. 0.9%), and ACME (15.4% vs. 5.1%), as well
as Staphylococcus haemolyticus mecA (90.5% vs. 10%) and IS 256 (61.9% vs. 10%).
The overall distribution of multilocus variable-number tandem-repeats analysis
(MLVA) types and sequence types was similar between the human milk of mothers of
preterm and term neonates, but a few mecA-IS 256-positive MLVA types colonized
only mothers of preterm neonates. Maternal hospitalization within 1 month
postpartum and the use of an arterial catheter or antibacterial treatment in the
neonate increased the odds of harboring mecA-positive staphylococci in human
milk. CONCLUSION: Limiting exposure of mothers of preterm neonates to the
hospital could prevent human milk colonization with more pathogenic
staphylococci.
PMID- 28418808
TI - Effects of Maternal Supplementation With Omega-3 Precursors on Human Milk
Composition.
AB - BACKGROUND: Long-chain polyunsaturated fatty acids (LC-PUFAs) are important for
newborn neurosensory development. Supplementation of breastfeeding mothers' diets
with omega-3 PUFAs, such as alpha-linolenic acid (ALA), may increase their
concentration in human milk. Research aim: This study aimed to assess human milk
composition after 15-day supplementation regimens containing either omega-3 PUFAs
or olive oil, which does not provide ALA. METHODS: A multicenter factorial
randomized trial was conducted with four groups of breastfeeding women, with each
group containing 19 to 22 women. After a 15-day ALA washout period, three groups
received supplementation with omega-3 precursors for 15 days: an enriched
margarine (M), a rapeseed oil (R), and a margarine and rapeseed oil (MR). The
fourth was unexposed to omega-3 precursors (olive oil control diet, O). After 15
days, blind determination of human milk fatty acid (FA) composition was assessed
by gas chromatography, and the FA composition was compared among groups using
variance analyses. RESULTS: Alpha-linolenic acid content, expressed as the mean
(standard deviation) total human milk FA percentage, was significantly higher
after diet supplementation with omega-3 PUFAs, with values of 2.2% (0.7%) (MR),
1.3% (0.5%) (R), 1.1% (0.4%) (M), and 0.8% (0.3%) (O at D30) ( p < .003 for each
comparison). The lowest LA-ALA ratio (5.5) was found in the MR group ( p < .001).
Docosahexaenoic acid and trans FA concentrations did not differ among groups.
CONCLUSION: In lactating women, omega-3 supplementation via the combination of
enriched margarine and rapeseed oil increased the ALA content of human milk and
generated the most favorable LA-ALA ratio for LC-PUFA synthesis.
PMID- 28418809
TI - Validation Study of Maternal Recall on Breastfeeding Duration 6 Years After
Childbirth.
AB - BACKGROUND: Breastfeeding duration is an important indicator commonly measured in
maternal and child health and nutrition research. Maternal short-term recall for
both initiation and duration of breastfeeding has been shown to be valid;
however, validity of long-term recall is not well understood. Research aim: This
study aims to assess the validity of maternal recall of breastfeeding duration 6
years after childbirth and its association with sociodemographic factors.
METHODS: Among 635 mother-child pairs, breastfeeding duration data collected
monthly throughout the 1st year after childbirth in the Infant Feeding Practices
Study II (IFPS II) were compared to recall data obtained 6 years later during the
Year 6 Follow-Up. The intraclass correlation coefficient (ICC) and Bland-Altman
plots were examined to study the agreement between the two data sets.
Sociodemographic factors associated with accurate recall to within 1 month of the
IFPS II breastfeeding duration were assessed using multivariable logistic
regression modeling. RESULTS: Maternal recall of breastfeeding duration was found
to be valid 6 years after childbirth with a small median overall bias (1 week)
toward overestimation. The overall concordance was high (ICC = 0.84), except for
high school graduates (ICC = 0.63) and smokers (ICC = 0.61). Smokers (adjusted
odds ratio = 0.52; 95% confidence interval [0.4, 0.8]) and multiparous women
(adjusted odds ratio = 0.57; 95% confidence interval [0.4, 0.9]) were also less
likely to give an accurate recall of their breastfeeding duration to within 1
month. CONCLUSION: Our study found that maternal recall of breastfeeding duration
varies by sociodemographic factors but is accurate 6 years after childbirth.
PMID- 28418810
TI - Relationship of Trochlear Morphology and Patellofemoral Joint Alignment to
Superolateral Hoffa Fat Pad Edema on MR Images in Individuals with or at Risk for
Osteoarthritis of the Knee: The MOST Study.
AB - Purpose To determine the relationship of patellofemoral joint alignment and
trochlear morphology to superolateral Hoffa fat pad (SHFP) edema on magnetic
resonance (MR) images in older adults with or at risk for osteoarthritis of the
knee. Materials and Methods Institutional review board approval and written
informed consent were obtained from all subjects. The Multicenter Osteoarthritis
Study is a prospective cohort study of older adults with or at risk for
osteoarthritis of the knee. Subjects were recruited from Birmingham, Alabama, and
Iowa City, Iowa. In this cross-sectional study, patellofemoral joint alignment
(bisect offset, patellar tilt angle, and Insall-Salvati ratio), trochlear
morphology (sulcus angle, lateral and medial trochlear inclination, and trochlear
angle) and SHFP edema were assessed on MR images of the knee. Measures of
alignment and morphology were divided into quartiles, and SHFP was determined to
be present or absent. Separate logistic regression models were used to determine
the relationship of each measure of alignment and morphology to the presence of
SHFP edema, with adjustments for age, sex, and body mass index. Results SHFP
edema was present in 152 (13.4%) of the 1134 knees that were included. When
compared with knees with measurements in the lowest quartile, knees with
measurements in the highest quartile for trochlear angle, bisect offset, and
Insall-Salvati ratios were 1.6 (95% confidence interval [CI]: 1.0, 2.6), 2.3 (95%
CI: 1.3, 4.0), and 8.9 (95% CI: 4.7, 16.9) times more likely to show SHFP edema,
respectively. No relationship was found between other measures and SHFP edema.
Conclusion A more anterior trochlear facet, a more laterally displaced patella,
and knees with patella alta were significantly associated with SHFP edema on MR
images in subjects with or at risk for osteoarthritis of the knee. (c) RSNA,
2017.
PMID- 28418812
TI - Phellinopsis lonicericola and P. tibetica spp. nov. (Hymenochaetales,
Basidiomycota), from Tibet, with a key to worldwide species.
AB - Phellinopsis (Hymenochaetaceae) was recently segregated from Phellinus.
Phellinopsis differs from other genera segregated from Phellinus in a combination
of hymenial setae, if present, mostly originating from tramal hyphae and hyaline
basidiospores becoming pale yellowish with age. In this study, two new species of
Phellinopsis, P. lonicericola and P. tibetica, from Tibet in southwestern China
were described and illustrated. Morphological data and sequences of the nuc rDNA
ITS1-5.8S-ITS2 region (internal transcribed spacer [ITS] barcode) support the
recognition of these taxa as distinct. They are morphologically compared with
other species of Phellinopsis. Notably, P. lonicericola was often found on
Lonicera together with Sanghuangporus alpinus, which was originally described
from the same locality. In addition, Phellinopsis helwingiae, known from a single
collection from Sichuan Province in midwestern China, is reported from Tibet.
Eight accepted species of Phellinopsis worldwide, each forming a terminal
lineage, grouped together as a strongly supported clade distinct from the clade
representing Phellinus. A key to the eight species of Phellinopsis is provided.
PMID- 28418811
TI - Hypertrabeculated Left Ventricular Myocardium in Relationship to Myocardial
Function and Fibrosis: The Multi-Ethnic Study of Atherosclerosis.
AB - Purpose To determine if excess greater left ventricle (LV) trabeculation is
associated with decreased average regional myocardial function, diffuse fibrosis,
or both. Materials and Methods This was a HIPAA-compliant institutional board
approved multicenter study, and all participants provided written informed
consent. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA)
underwent a comprehensive cardiac magnetic resonance (MR) examination. LV
trabeculation was measured with the maximal apical fractal dimension (FD), which
is a marker of endocardial complexity. Demographic covariates, cardiovascular
risk factors, and cardiac MR measurements were compared across quartiles of FD.
Associations between FD and peak regional systolic circumferential strain (Ecc)
and T1 time, a surrogate for diffuse myocardial fibrosis, were assessed with
multivariable linear regression models. Results A total of 1123 subjects (593
[52.8%] female; mean age, 67.1 years +/- 8.7 [standard deviation]) underwent FD
and Ecc measurement, and 992 (521 [52.5%] female; mean age, 67.1 years +/- 8.7)
underwent FD and T1 measurement. Mean FD was 1.2 +/- 0.07 in both groups, and
mean Ecc was -18.3 +/- 2.27 in the subjects who underwent FD and Ecc measurement.
Global volumes and ejection fraction showed no differences between FD quartiles.
However, with increasing FD quartile, Ecc was greater (indicating worse average
regional function) (P < .001). After adjustment, greater trabeculation was
associated with 21% worse myocardial strain (relative to the mean) per unit
change in FD (regression coefficient = 4.0%; P < .001). There was no association
between the degree of trabeculation and diffuse fibrosis measured with T1
mapping. Conclusion Average regional LV function was worse in individuals with
greater LV trabeculation, supporting the concept of hypertrabeculation being an
epiphenomenon of disease. (c) RSNA, 2017.
PMID- 28418813
TI - Radiation-Induced Deletions in Mouse Spermatogonia are Usually Large (over 200
kb) and Contain Little Sequence Similarity at the Junctions.
AB - Ionizing radiation can induce mutations, and the majority of radiation-induced
mutations in mammalian cells are deletions. The most critical types of radiation
induced DNA damage are DNA double-strand breaks, and these breaks are repaired by
either the homologous recombination (HR) pathway or the non-homologous end
joining (NHEJ) pathway. The HR pathway is not as mutagenic as the NHEJ pathway,
and it is expected that radiation-induced deletions would usually have little
sequence similarity around the deletion junction points. Here we report sequence
data from the regions around the rejoined junctions of 33 de novo copy-number
mutations (27 deletions and 6 duplications) obtained from offspring sired by male
mice that were irradiated at the spermatogonia stage and from nonirradiated
controls. The results indicate that deletions can be classified into three major
groups. In group 1, nine deletions were found to share long blocks of similar
sequences (200-6,000 bp) at the junctions and the deletion size varied
extensively (1 kb to 2 Mb) (e.g., illegitimate recombination). In group 2, five
deletions shared short identical sequences (0-7 bp) at the junctions, and the
deletion sizes were shorter than 200 kb (e.g., micro-homology-mediated repair).
Additional three-deletion candidates of this group were also found but turned out
to be inherited from mosaic parents. They are therefore not included in germline
mutations. In group 3, twelve deletions shared little sequence similarity (only 0
2 bp) at the junctions (likely due to NHEJ repair) and deletion sizes were longer
than 200 kb. Group 1 consisted of deletions found in both spontaneous and
irradiated genomes and thus, were probably caused by spontaneous events during
meiosis or DNA replication. Group 2 consisted mainly of deletions found in
nonexposed genomes. Group 3 consisted primarily of deletions that occurred in the
irradiated genomes. Among the duplications, we found no indication of any
association with radiation exposures. These results indicate that large size
(>200 kb) and little sequence similarity around the rejoined sites are likely to
be a hallmark of radiation-induced deletions in mice.
PMID- 28418814
TI - Ionizing Radiation Exposure During Pregnancy: Effects on Postnatal Development
and Life.
AB - Reliable human data on the effects of prenatal exposure to ionizing radiation are
largely based on high-dose exposures. Exposure to low doses may produce effects
that are not easily observable at birth, and may persist over the course of the
offspring's postnatal life. This is important when considering fetal programing,
a phenomenon characterized by changes in offspring phenotype due to a stress
experienced in utero. In this review, we briefly summarize the known effects of
both high- and low-dose exposure to ionizing radiation during pregnancy in
humans. There is a major consensus that the atomic bomb survivors' data shows
increased incidence of microcephaly and reductions in IQ of A-bomb survivors,
whereas, with diagnostic radiography in utero there is no conclusive evidence of
increased cancer risk. Due to the relatively limited data (particularly for low
dose exposures) in humans, animal models have emerged as an important tool to
study prenatal effects of radiation. These animal models enable researchers to
manipulate various experimental parameters and make it possible to analyze a
wider variety of end points. In this review, we discuss the major findings from
studies using mouse and rat models to examine prenatal ionizing radiation effects
in postnatal development of the offspring. In addition, we broadly categorize
trends across studies within three major stages of development: pre-implantation,
organogenesis and fetal development. Overall, long-term effects of prenatal
radiation exposure (including the possible role on the developmental programing
of disease) are important factors to consider when assessing radiation risk,
since these effects are of relevance even in the low-dose range.
PMID- 28418815
TI - Educational Activity for the Radiation Emergency System in the Northern Part of
Japan: Meeting Report on "The 3rd Educational Symposium on Radiation and Health
(ESRAH) by Young Scientists in 2016".
AB - In the northern part of Japan, close cooperation is essential in preparing for
any possible emergency response to radiation accidents because several
facilities, such as the Low-Level Radioactive Waste Disposal Facility, the MOX
Fuel Fabrication Plant and the Vitrified Waste Storage Center, exist in Rokkasho
Village (Aomori Prefecture). After the accident at Fukushima Daiichi Nuclear
Power Plant in 2011, special attention should be given to the relationship
between radiation and human health, as well as establishing a system for managing
with a radiation emergency. In the area of Hokkaido and Aomori prefectures in
Japan, since 2008 an exchange meeting between Hokkaido University and Hirosaki
University has been held every year to have opportunities to discuss radiation
effects on human health and to collect the latest news on monitoring
environmental radiation. This meeting was elevated to an international meeting in
2014 titled "Educational Symposium on Radiation and Health (ESRAH) by Young
Scientists". The 3rd ESRAH meeting took place in 2016, with the theme
"Investigating Radiation Impact on the Environmental and Health". Here we report
the meeting findings on the continuing educational efforts after the Fukushima
incident, what was accomplished in terms of building a community educational
approaches, and future goals.
PMID- 28418816
TI - Safe and competent opioid prescribing education: Increasing dissemination with a
train-the-trainer program.
AB - BACKGROUND: Due to the high prevalence of prescription opioid misuse, the US Food
and Drug Administration (FDA) mandated a Risk Evaluation and Mitigation Strategy
(REMS) requiring manufacturers of extended-release/long-acting (ER/LA) opioids to
fund continuing education based on an FDA curricular Blueprint. This paper
describes the Safe and Competent Opioid Prescribing Education (SCOPE of Pain)
train-the-trainer program and its impact on (1) disseminating the SCOPE of Pain
curriculum and (2) knowledge, confidence, attitudes, and performance of the
participants of trainer-led compared with expert-led meetings. METHODS: SCOPE of
Pain is a 3-hour ER/LA opioid REMS education. In addition to expert-led live
statewide meetings, a 2-hour train-the-trainer (TTT) workshop was developed to
increase dissemination nationally. The trainers were expected to conduct SCOPE of
Pain meetings at their institutions. Participants of both the trainer-led and
expert-led SCOPE of Pain programs were surveyed immediately post and 2 months
post meetings to assess improvements in knowledge, confidence, attitudes, and
self-reported safe opioid prescribing practices. RESULTS: During 9 months (May
2013 to February 2014), 89 trainers were trained during 9 TTT workshops in 9
states. Over 24 months (May 2013 to April 2015), 33% of the trainers conducted at
least 1 SCOPE of Pain training, with a total of 79 meetings that educated 1419
participants. The average number of meetings of those who conducted at least 1
meeting was 2.8 (range: 1-19). The participants of the trainer-led programs were
significantly more likely to be practicing in rural settings than those who
participated in the expert-led meetings (39% vs. 26%, P < .001). At 2 months post
training, there were no significant differences in improvements in participant
knowledge, confidence, attitudes, and performance between expert-led and trainer
led meetings. CONCLUSIONS: The SCOPE of Pain TTT program holds promise as an
effective dissemination strategy to increase guideline-based safe opioid
prescribing knowledge, confidence, attitudes, and self-reported practices.
PMID- 28418817
TI - Virtual Mapping of the Frontal Recess: Guiding Safe and Efficient Frontal Sinus
Surgery.
AB - : Objective To define relationships between the frontal sinus opening, ostia of
other frontal recess cells, and endoscopic landmarks and to develop a clinically
useful framework to guide frontal sinus surgery. Study Design Retrospective
review. Setting Tertiary care academic referral center. Methods Adult patients
with computed tomography (CT) without sinonasal pathology were included. Virtual
endoscopy (using OsiriX) and corresponding CT reconstructions were used to
identify all visible ostia in the frontal recess and characterize their positions
in spaces between the uncinate/agger nasi (U), bulla ethmoidalis (EB), and middle
turbinate (MT). Results Two hundred sides in 100 patients (median age 51 years,
62% female) were analyzed. The "center" of each map was defined as the
intersection of spaces between U, EB, and MT. The frontal sinus opening was in
the "center" in 53% of frontal recesses, lateral to this position in 29%, and
anterior in 11%. When the frontal sinus opening was at the "center," anterior
ostia drained frontal Kuhn T cells in 51% and intersinus septal cells in 23%. The
skull base attachment of the apical strut of the uncinate process demarcated
medial and lateral within the space between U and EB, with the opening to the
frontal sinus medial in 68% and lateral in 31%. Left-right asymmetry in frontal
sinus openings was noted in 46% of patients. Conclusion Combining preoperative
imaging and knowledge of these anatomic relationships may facilitate more
efficient frontal outflow tract identification and instrumentation. This
represents the first and largest description of ostial configurations relative to
endoscopic structural landmarks. LEVEL OF EVIDENCE: 4.
PMID- 28418818
TI - "It is not the diet; it is the mental part we need help with." A multilevel
analysis of psychological, emotional, and social well-being in obesity.
AB - In this research, we explored the psychological, emotional, and social
experiences of individuals living with obesity, and perceptions of health care
providers. We conducted a theoretical thematic analysis using two theoretical
frameworks applied to transcripts from a previous qualitative study. Themes from
a mental well-being framework were subsequently categorized under five
environmental levels of the Social-Ecological Model (SEM). Key mental well-being
themes appeared across all levels of the SEM, except the policy level. For the
individual environment, one main theme was food as a coping mechanism and source
of emotional distress. In the interpersonal environment, two themes were (a)
blame and shame by family members and friends because of their weight and (b)
condemnation and lack of support from health professionals. In the organizational
environment, one main theme was inadequate support for mental well-being issues
in obesity management programmes. In the community environment, one major theme
the negative mental well-being impact of the social stigma of obesity. An
overarching theme of weight stigma and bias further shaped the predominant themes
in each level of the SEM. Addressing weight stigma and bias, and promoting
positive mental well-being are two important areas of focus for supportive
management of individuals living with obesity.
PMID- 28418819
TI - Cancer Genomics and Important Oncologic Mutations: A Contemporary Guide for Body
Imagers.
AB - The field of cancer genomics is rapidly evolving and has led to the development
of new therapies. Knowledge of commonly involved cellular pathways and genetic
mutations is now essential for radiologists reading oncology cases. Radiogenomics
is an emerging area of research that seeks to correlate imaging features with
cancer genotypes. Such knowledge may extend the utility of multiparametric
imaging to yield information regarding cancer prognosis and likelihood of
therapeutic response. To date, only a handful of radiogenomics studies have been
performed to evaluate solid tumors of the body, and there is much to explore.
Before doing so, however, it behooves us to have adequate background knowledge of
clinical cancer genomics to design meaningful radiogenomics projects and explore
imaging phenotypes. Herein, an up-to-date, detailed overview is provided of well
known and common mutations of solid body tumors (such as human epithelial growth
factor receptor 2, breast cancer susceptibility protein), newer genomic
alterations with potential for clinical relevance, and a discussion of known
related imaging findings, including existing radiogenomics data and other
radiologic patterns of disease. (c) RSNA, 2017 Online supplemental material is
available for this article.
PMID- 28418820
TI - Case 241: Hemiparkinsonism- Hemiatrophy-SPECT with 99mTc TRODAT-1 and Muscle MR
Imaging Abnormalities.
AB - History A 43-year-old right-handed man presented with a history of progressive
mild left-sided weakness and slowness of movements. Symptoms began 4 years
earlier, and the patient noticed a progressive decline in his daily routine due
to gait difficulties in the past year. There was no history of head trauma,
surgery, drug therapy, smoking, or alcohol abuse, nor was there any relevant
family history. Examination revealed normal cognition (29 of 30 points on the
Mini-Mental State Examination and 27 of 30 points on the Montreal Cognitive
Assessment) and normal cerebellar, sensory, cranial nerve, and autonomic
function. There was mild left-sided weakness involving the upper and lower limbs
(medical research council graded muscle strength as 4+ out of 5) that was
associated with facial hypomimia and a rigid akinetic syndrome only in the
patient's left hemibody (Unified Parkinson's Disease Rating Scale [UPDRS] part
III [motor examination], 23 out of 52 points). Mild atrophy in the left upper and
lower limbs without pain, swelling, or skin lesions was noted at physical
examination. Routine blood chemistry was normal, as were serum creatine kinase
and aldolase levels and thyroid, hepatic, and renal function. T1- and T2
weighted, fluid-attenuated inversion recovery, diffusion- and perfusion-weighted,
and contrast material-enhanced brain magnetic resonance (MR) imaging results were
normal, without basal ganglia hyperintensity, lacunae, calcification, or heavy
metal deposits. Muscle MR imaging and single photon emission computed tomography
(SPECT) with technetium 99m (99mTc) tropane dopamine transporter (TRODAT)-1 were
performed for further evaluation. This patient received levodopa and benserazide
(200 and 50 mg, respectively) four times a day and amantadine (100 mg) three
times a day without adequate improvement (UPDRS score decreased from 23 to 20
points).
PMID- 28418821
TI - In Memoriam.
PMID- 28418824
TI - Financial Forecasting and Stochastic Modeling: Predicting the Impact of Business
Decisions.
AB - In health care organizations, effective investment of precious resources is
critical to assure that the organization delivers high-quality and sustainable
patient care within a supportive environment for patients, their families, and
the health care providers. This holds true for organizations independent of size,
from small practices to large health systems. For radiologists whose role is to
oversee the delivery of imaging services and the interpretation, communication,
and curation of imaging-informed information, business decisions influence where
and how they practice, the tools available for image acquisition and
interpretation, and ultimately their professional satisfaction. With so much at
stake, physicians must understand and embrace the methods necessary to develop
and interpret robust financial analyses so they effectively participate in and
better understand decision making. This review discusses the financial drivers
upon which health care organizations base investment decisions and the central
role that stochastic financial modeling should play in support of strategically
aligned capital investments. Given a health care industry that has been slow to
embrace advanced financial analytics, a fundamental message of this review is
that the skills and analytical tools are readily attainable and well worth the
effort to implement in the interest of informed decision making. (c) RSNA, 2017
Online supplemental material is available for this article.
PMID- 28418825
TI - Science to Practice: Quantitative US Elastography Can Be Used to Quantify
Mechanical and Histologic Tendon Healing in a Rabbit Model of Achilles Tendon
Transection.
AB - Compression-based ultrasonographic (US) elastography is associated with time
dependent mechanical and histologic changes of the healing tendon in a transected
rabbit model of the Achilles tendon. This finding will lead to continued
development of quantitative US, which can be used to objectively assess a
diseased or healing tendon. With advances in the method used, clinical
translation of tendon elastography may enable clinicians to diagnose tendon
damage and track healing, which should improve both treatment and outcome.
PMID- 28418827
TI - Case 245.
PMID- 28418828
TI - A comparison of blood and cerebrospinal fluid cytokines (IL-1beta, IL-6, IL-18,
TNF-alpha) in neonates with perinatal hypoxia.
AB - Perinatal hypoxia-ischemia is a specific and important pathological event in
neonatal care practice. The data on relationship between the concentrations of
cytokines in blood and cerebrospinal fluid (CSF) and perinatal brain injury are
scarce. The aim of this study is to evaluate changes in interleukin (IL-1beta, IL
6, and IL-18) and tumor necrosis factor alpha (TNF-alpha) levels in newborns with
perinatal hypoxia (PNH). CSF and serum samples of 35 term and near-term (35-40
weeks) newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme
linked immunosorbent assay. Control group consisted of 25 non-asphyxic/non
hypoxic infants of the same age sampled for clinically suspected perinatal
meningitis, but proven negative and healthy otherwise. The cytokine values in CSF
and serum samples were determined in relation to initial hypoxic-ischemic
encephalopathy (HIE) staged according the Sarnat/Sarnat method, and compared with
neurological outcome at 12 months of age estimated using Amiel-Tison procedure.
The concentrations of IL-6 and TNF-alpha in serum of PNH patients were
significantly higher compared to control group (p = 0.0407 and p = 0.023,
respectively). No significant difference between average values of cytokines in
relation to the stage of HIE was observed. Significantly higher levels of IL-6
and IL-18 corresponded to a mildly abnormal neurological outcome, while higher
levels of IL-6 and TNF-alpha corresponded to a severely abnormal neurological
outcome, at 12 months of age. Elevated serum levels of IL-6 and TNF-alpha better
corresponded with hypoxia/ischemia compared to CSF values, within 96 hours of
birth. Also, higher serum levels of IL-6, TNF-alpha, and IL-18 corresponded
better with abnormal neurological outcome at 12 months of age, compared to CSF
values.
PMID- 28418829
TI - CTX-M-27-Producing Escherichia coli of Sequence Type 131 and Clade C1-M27,
France.
PMID- 28418832
TI - The Glossary of Prosthodontic Terms: Ninth Edition.
PMID- 28418830
TI - Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B.
mallei-like Variation in the bimA Motility Gene, Australia.
AB - Neurologic melioidosis is a serious, potentially fatal form of Burkholderia
pseudomallei infection. Recently, we reported that a subset of clinical isolates
of B. pseudomallei from Australia have heightened virulence and potential for
dissemination to the central nervous system. In this study, we demonstrate that
this subset has a B. mallei-like sequence variation of the actin-based motility
gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles,
isolates that contain the B. mallei-like variation demonstrate increased
persistence in phagocytic cells and increased virulence with rapid systemic
dissemination and replication within multiple tissues, including the brain and
spinal cord, in an experimental model. These findings highlight the implications
of bimA variation on disease progression of B. pseudomallei infection and have
considerable clinical and public health implications with respect to the degree
of neurotropic threat posed to human health.
PMID- 28418831
TI - The Evaluation of Benefit of Newly Prepared Reversible Inhibitors of
Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological
Pretreatment of Soman-Poisoned Mice.
AB - AIM: The ability of four newly prepared reversible inhibitors of
acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and
currently used carbamate pyridostigmine to increase the resistance of mice
against soman and the efficacy of antidotal treatment of soman-poisoned mice was
evaluated. METHODS: The evaluation of the effect of pharmacological pretreatment
is based on the identification of changes of soman-induced toxicity that was
evaluated by the assessment of its LD50 value and its 95% confidence limit using
probitlogarithmical analysis of death occurring within 24 h after administration
of soman. RESULTS: 6-chlorotacrine was only able to markedly protect mice against
acute toxicity of soman. In addition, the pharmacological pretreatment with 6
chlorotacrine or compound 2 was able to increase the efficacy of antidotal
treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice.
The other newly prepared reversible inhibitors of acetylcholinesterase (7
phenoxytacrine, compound 1) as well as commonly used pyridostigmine did not
influence the efficacy of antidotal treatment. CONCLUSION: These findings
demonstrate that pharmacological pretreatment of somanpoisoned mice can be
promising and useful in the case of administration of 6-chlorotacrine and partly
compound 2.
PMID- 28418833
TI - Willingness to Pay in Caregivers of Patients Affected by Schizophrenia.
AB - BACKGROUND: Schizophrenia is a debilitating disorder that often requires the
affected individual to receive care from a caregiver. Willingness to Pay (WTP)
technique allows a valuation of the health state preferences by assessing the
impact of the disease and translating it into monetary terms. AIMS OF THE STUDY:
The objective was to determine the WTP of schizophrenic patients' caregivers on a
hypothetical recovery scenario and correlate it to socio-demographic and clinical
characteristics, Knowledge of Disease, Quality of life and Burden of Disease.
METHODS: A convenience sample consecutively assessed 189 outpatients' caregivers
from Schizophrenia Program of Federal University of Sao Paulo. A single caregiver
was considered for each patient, taking into consideration their close
relationship and their direct involvement in the treatment. Open WTP
questionnaire for a hypothetical schizophrenia recovery scenario, KAST (Knowledge
of Disease), SF-6D (Quality of life) and ZBI-22 (Burden of Disease) scales were
applied. RESULTS: A monthly WTP mean value (SD) of US?USD 63.63 (111.88) was
found. The average value (SD) found was 12.96 (2.45) on KAST, 0.78 (0.08) on SF6D
and 29.91 (16.10) on ZARIT. Income, education, social class, knowledge of disease
and burden of caregiver were positively correlated to the WTP value. By linear
regression model, income and education remained significant. CONCLUSION:
Willingness to Pay (WTP) is a method that can be used to determine the strength
of preference of patients and caregivers for a recovery in schizophrenia. The
higher the income and education, the higher the willingness to pay. No clinical
characteristics of patients had a statistically significant relation to the value
the caregiver would pay. IMPLICATIONS FOR HEALTH POLICIES: WTP is a potentially
useful tool to determine values and health care preferences, and can be used for
the development of mental health policies. IMPLICATIONS FOR FURTHER RESEARCH:
Future research should be used to enhance WTP tool in mental health studies on
the impact of diseases, including schizophrenia.
PMID- 28418834
TI - Reduction in Costs after Treating Comorbid Panic Disorder with Agoraphobia and
Generalized Anxiety Disorder.
AB - BACKGROUND: Panic disorder with agoraphobia (PDA) and generalized anxiety
disorder (GAD) are impairing and costly disorders that are often misdiagnosed and
left untreated despite multiple consultations. These disorders frequently co
occur, but little is known about the costs associated with their comorbidity and
the impact of cognitive-behavioral therapy (CBT) on cost reduction. AIMS OF THE
STUDY: The first objective of this study was to assess the mental health-related
costs associated with the specific concomitance of PDA and GAD. The second aim
was to determine whether there is a reduction in direct and indirect mental
health-related costs following conventional CBT for the primary disorder only
(PDA or GAD) or combined CBT adapted to the comorbidity (PDA and GAD). METHODS: A
total of 123 participants with a double diagnosis of PDA and GAD participated in
this study. Direct and indirect mental health-related costs were assessed and
calculated from a societal perspective at the pre-test, the post-test, and the
three-month, six-month and one-year follow-ups. RESULTS: At the pre-test, PDA-GAD
comorbidity was found to generate a mean total cost of CADUSD 2,000.48 (SD = USD
2,069.62) per participant over a three-month period. The indirect costs were much
higher than the direct costs. Both treatment modalities led to significant and
similar decreases in all cost categories from the pre-test to the post-test. This
reduction was maintained until the one-year follow-up. DISCUSSION: Methodological
choices may have underestimated cost evaluations. Nonetheless, this study
supports the cost offset effects of both conventional CBT for primary PDA or GAD
and combined CBT for PDA-GAD comorbidity. IMPLICATIONS FOR HEALTHCARE PROVISION
AND USE: Treatment of comorbid and costly disorders with evidence-based
treatments such as CBT may lead to considerable economic benefits for society.
IMPLICATIONS FOR HEALTH POLICIES: Considering the limited resources of healthcare
systems, it is important to make choices that will lead to better accessibility
of quality services. The application of CBT for PDA, GAD or both disorders and
training mental health professionals in this therapeutic approach should be
encouraged. Additionally, it would be favorable for insurance plans to reimburse
employees for expenses associated with psychological treatment for anxiety
disorders. IMPLICATIONS FOR FURTHER RESEARCH: In addition to symptom reduction,
it would be of great pertinence to explore which factors can contribute to
reducing direct and indirect mental health-related costs.
PMID- 28418835
TI - Costs and Effectiveness of Treating Homeless Persons with Cocaine Addiction with
Alternative Contingency Management Strategies.
AB - BACKGROUND: Between 1990 and 2006 in Birmingham, Alabama USA, 4 separate
randomized controlled studies, called "Homeless 1" through "Homeless 4", treated
cocaine substance abuse among chronically homeless adults, largely black men,
many with non-psychotic mental health problems. The 4 studies had 9 treatment
arms that used various counseling methods plus, in some arms, the provision of
housing and work therapy usually with a contingent requirement of urine-test
verified abstinence from substances. Participants in the abstinent-contingent
arms who lapsed on abstinence were removed from housing and sent to an evening
public shelter from which they were daily transported to day treatment until they
returned to abstinence. AIMS OF THE STUDY: This paper compares the cost
effectiveness of the treatment arms. METHODS: Societal cost per participant (in
2014 dollars) for each arm is defined as direct treatment cost plus cost of jail
or hospital plus societal expense of public shelter use by lapsed participants.
An untreated Base Case is defined as 5 percent abstinence with 95 percent usage
of a public shelter. Incremental Cost Effectiveness Ratios (ICERs) for paired
arms are defined as the change in cost per participant divided by the change in
abstinence. Bootstrapping estimates confidence intervals. RESULTS: Average cost
per participant at the end of 6 months of active treatment in 7 arms with
comparable data ranged from USD 10,447 to USD 36,194 with corresponding average
weeks abstinent ranging from 6.1 to 15.3 out of a possible 26 weeks. In contrast,
the Base Case would cost USD 6,123 for 1.3 weeks of abstinence. Compared to the
Base Case, the least expensive "DT2" treatment has an ICER of USD 901 (95% CI =
USD 571 to USD 1,681) per additional week of abstinence and the most expensive
"CMP4" has an ICER of USD 2,147 (95% CI = USD 1,701 to USD 2,848). Additionally,
the Homeless 3 study found that the abstinent contingent housing (ACH3) treatment
compared to the Non Abstinent Contingent Housing (NAC3), analogous to "Housing
First", achieved better abstinence (12.1 v. 10 weeks) at higher average cost (USD
22,512 v. USD 17,541) yielding an ICER for this comparison of (USD 2,367, 95%
CI=USD -10,587 to USD 12,467). Similar results are found at 12 months (6 months
after active treatment). DISCUSSION: More intensive methods of counseling
improved abstinence but 4 of the 7 treatments were inefficient ("dominated").
Bootstrapping shows that results are sensitive to which individuals were randomly
assigned to each arm. A limitation of the analysis is that it does not consider
the full societal cost of lost wages, crime costs beyond jail expenses and
deterioration of neighborhood quality of life. Additionally, populations treated
by Housing First programs may differ from the Birmingham Homeless studies in the
severity of addiction or co-occuring psychological problems. IMPLICATIONS FOR
TREATMENT: The Homeless studies show that abstinent contingent safe housing with
counseling can substantially improve abstinence for homeless cocaine abusers.
Incremental costs rise sharply with more intensive counseling; modest programs of
counseling may be more cost effective in a stepped treatment strategy.
PMID- 28418836
TI - PERSPECTIVES: Accountability for Mental Health: The Australian Experience.
AB - BACKGROUND: Australia was one of the first countries to develop a national policy
for mental health. A persistent characteristic of all these policies has been
their reference to the importance of accountability. What does this mean exactly
and have we achieved it? Can Australia tell if anybody is getting better? AIMS OF
THE STUDY: To review accountability for mental health in Australia and question
whether two decades of Australian rhetoric around accountability for mental
health has been fulfilled. METHODS: This paper first considers the concept of
accountability and its application to mental health. We then draw on existing
literature, reports, and empirical data from national and state governments to
illustrate historical and current approaches to accountability for mental health.
We provide a content analysis of the most current set of national indicators. The
paper also briefly considers some relevant international processes to compare
Australia's progress in establishing accountability for mental health. RESULTS:
Australia's federated system of government permits competing approaches to
accountability, with multiple and overlapping data sets. A clear national
approach to accountability for mental health has failed to emerge. Existing data
focuses on administrative and health service indicators, failing to reflect
broader social factors which reveal quality of life. In spite of twenty years of
investment and effort Australia has been described as outcome blind, unable to
demonstrate the merit of USD 8bn spent on mental health annually. DISCUSSION AND
LIMITATIONS: While it may be prolific, existing administrative data provide
little outcomes information against which Australia can genuinely assess the
health and welfare of people with a mental illness. International efforts are
evolving slowly. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Even in high
income countries such as Australia, resources for mental health services are
constrained. Countries cannot afford to continue to invest in services or
programs that fail to demonstrate good outcomes for people with a mental illness
or are not value for money. IMPLICATIONS FOR HEALTH POLICIES: New approaches are
needed which ensure that chosen accountability indicators reflect national health
and social priorities. Such priorities must be meaningful to a range of
stakeholders and the community about the state of mental health. They must drive
an agenda of continuous improvement relevant to those most affected by mental
disorders. These approaches should be operable in emerging international
contexts. IMPLICATIONS FOR FURTHER RESEARCH: Australia must further develop its
approach to health accountability in relation to mental health. A limited set of
new preferred national mental health indicators should be agreed. These should be
tested, both domestically and internationally, for their capacity to inform and
drive quality improvement processes in mental health. CONCLUSION: Existing
systems of accountability are not fit for purpose, incapable of firing necessary
quality improvement processes. Supported by adequate resources, realistic targets
and a culture of openness, new accountability could drive real quality
improvement processes for mental health, facilitate jurisdictional comparisons in
Australia, and contribute to new efforts to benchmark mental health
internationally.
PMID- 28418837
TI - Rapamycin promotes differentiation increasing betaIII-tubulin, NeuN, and NeuroD
while suppressing nestin expression in glioblastoma cells.
AB - Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation
which relates to a variety of effects such as: lower survival, higher
infiltration, high stemness and radio- and chemo-resistance. Recently, it was
demonstrated that mTOR may produce a gene shift leading to altered protein
expression. Therefore, in the present study we administered different doses of
the mTOR inhibitor rapamycin to explore whether the transcription of specific
genes are modified. By using a variety of methods we demonstrate that rapamycin
stimulates gene transcription related to neuronal differentiation while
inhibiting stemness related genes such as nestin. In these experimental
conditions, cell phenotype shifts towards a pyramidal neuron-like shape owing
long branches. Rapamycin suppressed cell migration when exposed to fetal bovine
serum (FBS) while increasing the cell adhesion protein phospho-FAK (pFAK). The
present study improves our awareness of basic mechanisms which relate mTOR
activity to the biology of glioblastoma cells. These findings apply to a variety
of effects which can be induced by mTOR regulation in the brain. In fact, the
ability to promote neuronal differentiation might be viewed as a novel
therapeutic pathway to approach neuronal regeneration.
PMID- 28418839
TI - Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP
induced purinergic signalling and cell migration in human hepatocellular
carcinoma cells.
AB - Extracellular ATP-induced Ca2+ signalling is critical in regulating diverse
physiological and disease processes. Emerging evidence suggests high
concentrations of extracellular ATP in tumour tissues. In this study, we examined
the P2 receptor for ATP-induced Ca2+ signalling in human hepatocellular carcinoma
(HCC) cells. Fura-2-based measurements of the intracellular Ca2+ concentration
([Ca2+]i) showed that extracellular ATP induced an increase in the [Ca2+]i in
human HCC Huh-7 and HepG2 cells. NF546, a P2Y11 receptor agonist was equally
effective in inducing an increase in the [Ca2+]i. In contrast, agonists for the
P2X receptors (alphabetameATP and BzATP), P2Y1 receptor (MRS2365) or P2Y2
receptor (MRS2768) were ineffective. In addition, ATP/NF546-induced increases in
the [Ca2+]i were strongly inhibited by treatment with NF340, a P2Y11 receptor
antagonist. Immunofluorescent confocal imaging and western blotting analysis
consistently demonstrated the P2Y11 receptor expression in Huh-7 and HepG2 cells.
Transfection with P2Y11-specific siRNA attenuated the P2Y11 receptor protein
expression level and also reduced NF546-induced increase in the [Ca2+]i.
Importantly, immunohistochemistry revealed that the P2Y11 receptor was expressed
at very high level in human HCC tissues and, by contrast, it was barely detected
in normal liver tissues. Trans-well cell migration assay demonstrated that ATP
and NF546 induced concentration-dependent stimulation of Huh-7 cell migration.
Treatment with NF340 prevented ATP-induced stimulation of cell migration. Taken
together, our results show carcinoma-specific expression of the P2Y11 receptor
and its critical role in mediating ATP-inducing Ca2+ signalling and regulating
cell migration in human HCC cells.
PMID- 28418840
TI - Distinct MDCT imaging features to differential diagnosis of hepatic
paragonimiasis and small hepatocellular carcinoma.
AB - We used multi-row detector computed tomography (MDCT) to identify the
distinguishing characteristics of hepatic paragonimiasis and small hepatocellular
carcinoma lesions. We analyzed a cohort of 60 patients, of which 26 had hepatic
paragonimiasis and 34 with a small (<= 3cm) hepatocellular carcinoma. MDCT
detected 65 lesions that were retrospectively reviewed and analyzed based on
their imaging features. Both groups showed distinct MDCT imaging features that
could contribute to an accurate diagnosis. In the paragonimiasis group, 75%
(21/28) lesions were located in the hepatic subcapsular region, whereas only
10.8% (4/37) of lesions in the hepatocellular carcinoma group were subcapsular.
Most hepatic paragonimiasis lesions (57.1%; 16/28) also showed characteristic
tubular or tunnel features that were not present in hepatocellular carcinomas.
Further, 71.4% (20/28) paragonimiasis lesions were rim enhanced with irregular
tract-like non-enhanced internal areas with a characteristic target loop, while
94.6% (35/37) of small hepatocellular carcinoma lesions showed homogenous
enhancement in the arterial and venous phase. In addition, the period CT values
for hepatic paragonimiasis were less than those of hepatic carcinomas (P<0.001).
These clinically significant findings illustrate the diagnostic features that
enable one to distinguish hepatic paragonimiasis from small hepatocellular
carcinomas.
PMID- 28418841
TI - Circulating uric acid levels and subsequent development of cancer in 493,281
individuals: findings from the AMORIS Study.
AB - OBJECTIVES: Serum uric acid has been suggested to be associated with cancer risk.
We aimed to study the association between serum uric acid and cancer incidence in
a large Swedish cohort. RESULTS: A positive association was found between uric
acid levels and overall cancer risk, and results were similar with adjustment for
glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th
quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and
1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association
between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma
skin, and other cancers in men and of head and neck and other cancers in women.
An inverse association was observed for pulmonary and central nervous system
(CNS) cancers in men and breast, lymphatic and haematological, and CNS
malignancies in women. MATERIALS AND METHODS: We included 493,281 persons aged 20
years and older who had a measurement of serum uric acid and were cancer-free at
baseline in the AMORIS study. Multivariable Cox proportional hazards regression
was used to investigate sex-specific quartiles of serum uric acid in relation to
cancer risk in men and women. Analysis was further adjusted for serum glucose,
triglycerides and, where available, BMI. Site-specific analysis was performed for
major cancers. CONCLUSIONS: Altered uric acid levels were associated with risk of
overall and some specific cancers, further indicating the potential role of uric
acid metabolism in carcinogenesis.
PMID- 28418842
TI - Effects of TLR-2/NF-kappaB signaling pathway on the occurrence of degenerative
knee osteoarthritis: an in vivo and in vitro study.
AB - The study aims to explore the effects of TLR-2/NF-kappaB signaling pathway on the
occurrence of degenerative knee osteoarthritis (OA). Degenerative knee OA and
normal cartilage samples were collected from patients with degenerative knee OA
receiving total knee arthroplasty and amputation. Expressions of TLR-2, NF-kappaB
and MMP-13 were determined by qRT-PCR and immunochemistry. The chondrocytes were
divided into control, IL-1beta, IL-1beta + anti-TLR-2 and IL-1beta + PDTC groups.
MTT assay and flow cytometry were performed to determine proliferation and
apoptosis of the chondrocytes. Expressions of TLR-2, NF-kappaB and MMP-13 were
measured by Western blotting. ELISA was conducted to detect the expressions of
related inflammatory factors. The positive expressions of TLR, NF-kappaB and
MMP13 were associated with body mass index (BMI), family history, exercise, and
WOMAC scores of OA patients. Logistic regression analysis showed that OA
influencing factors were TLR, NF-kappaB, MMP13, BMI, family history and exercise.
Compared with normal chondrocytes, the expressions of TLR-2, NF-kappaB, MMP-13
and related inflammatory factors increased in degenerative knee OA. The
chondrocytes in the IL-1beta + anti-TLR-2 and IL-1beta + PDTC groups showed lower
apoptosis rates than those in the IL-1beta group. Compared with the control
group, increased expressions of TLR-2, NF-kappaB, phosphorylated-NF-kappaB (p-NF
kappaB), MMP-13, IL-1, IL-6 and TNF-alpha were found in the IL-1beta group. In
the IL-1beta + anti-TLR-2 and IL-1beta + PDTC groups, decreased expressions of NF
kappaB, p-NF-kappaB, MMP-13, IL-1, IL-6 and TNF-alpha were found compared with
those in the IL-1beta group. TLR-2/NF-kappaB signaling pathway contributes to the
occurrence of degenerative knee OA.
PMID- 28418843
TI - CD24 Expression and differential resistance to chemotherapy in triple-negative
breast cancer.
AB - Breast cancer (BC) is a leading cause of cancer-related death in women. Adjuvant
systemic chemotherapies are effective in reducing risks of recurrence and have
contributed to reduced BC mortality. Although targeted adjuvant treatments
determined by biomarkers for endocrine and HER2-directed therapies are largely
successful, predicting clinical benefit from chemotherapy is more challenging.
Drug resistance is a major reason for treatment failures. Efforts are ongoing to
find biomarkers to select patients most likely to benefit from chemotherapy.
Importantly, cell surface biomarkers CD44+/CD24- are linked to drug resistance in
some reports, yet underlying mechanisms are largely unknown. This study focused
on the potential role of CD24 expression in resistance to either docetaxel or
doxorubicin in part by the use of triple-negative BC (TNBC) tissue microarrays.
In vitro assays were also done to assess changes in CD24 expression and
differential drug susceptibility after chemotherapy. Further, mouse tumor
xenograft studies were done to confirm in vitro findings. Overall, the results
show that patients with CD24-positive TNBC had significantly worse overall
survival and disease-free survival after taxane-based treatment. Also, in vitro
cell studies show that CD44+/CD24+/high cells are more resistant to docetaxel,
while CD44+/CD24-/low cells are resistant to doxorubicin. Both in vitro and in
vivo studies show that cells with CD24-knockdown are more sensitive to docetaxel,
while CD24-overexpressing cells are more sensitive to doxorubicin. Further,
mechanistic studies indicate that Bcl-2 and TGF-betaR1 signaling via ATM-NDRG2
pathways regulate CD24. Hence, CD24 may be a biomarker to select
chemotherapeutics and a target to overcome TNBC drug resistance.
PMID- 28418844
TI - Loss of tumour-specific ATM protein expression is an independent prognostic
factor in early resected NSCLC.
AB - Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity.
In response to DNA double-strand breaks, ATM phosphorylates downstream proteins
involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we
investigate the frequency, and influence of ATM deficiency on outcome, in early
resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165
formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed
at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were
analyzed for ATM expression using quantitative fluorescence immunohistochemistry.
Both malignant cell-specific ATM expression and the ratio of ATM expression
within malignant tumour cells compared to that in the surrounding tumour stroma,
defined as the ATM expression index (ATM-EI), were measured and correlated with
clinical outcome. ATM loss was identified in 21.8% of patients, and was
unaffected by clinical pathological variables. Patients with low ATM-EI tumours
had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This
effect was pronounced in stage II/III patients, even after adjusting for other
clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM
deficient patients may derive greater benefit from guideline-recommended adjuvant
chemotherapy following surgical resection. Taken together, these results indicate
that ATM loss seems to be an early event in NSCLC carcinogenesis and is an
independent prognostic factor associated with worse survival in stage II/III
patients.
PMID- 28418845
TI - Preclinical development of G1T38: A novel, potent and selective inhibitor of
cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with
CDK4/6 sensitive tumors.
AB - Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic
strategy for the treatment of estrogen receptor positive (ER+) breast cancer.
Although efficacious, current treatment regimens require a dosing holiday due to
severe neutropenia potentially leading to an increased risk of infections, as
well as tumor regrowth and emergence of drug resistance. Therefore, a next
generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent
tumors while minimizing neutropenia could reduce both the need for treatment
holidays and the risk of inducing drug resistance.Here, we describe the
preclinical characterization and development of G1T38; a novel, potent,
selective, and orally bioavailable CDK4/6 inhibitor. In vitro, G1T38 decreased
RB1 (RB) phosphorylation, caused a precise G1 arrest, and inhibited cell
proliferation in a variety of CDK4/6-dependent tumorigenic cell lines including
breast, melanoma, leukemia, and lymphoma cells. In vivo, G1T38 treatment led to
equivalent or improved tumor efficacy compared to the first-in-class CDK4/6
inhibitor, palbociclib, in an ER+ breast cancer xenograft model. Furthermore,
G1T38 accumulated in mouse xenograft tumors but not plasma, resulting in less
inhibition of mouse myeloid progenitors than after palbociclib treatment. In
larger mammals, this difference in pharmacokinetics allowed for 28 day continuous
dosing of G1T38 in beagle dogs without producing severe neutropenia. These data
demonstrate G1T38 has unique pharmacokinetic and pharmacodynamic properties,
which result in high efficacy against CDK4/6 dependent tumors while minimizing
the undesirable on-target bone marrow activity, thus potentially allowing G1T38
to be used as a continuous, daily oral antineoplastic agent.
PMID- 28418846
TI - Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery
for brain tumor therapy.
AB - Convection-enhanced delivery (CED) is a promising technique for infusing a
therapeutic agent through a catheter with a pressure gradient to create bulk flow
for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd
DTPA) is the most commonly applied surrogate agent for predicting drug
distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides
only a short observation duration, and concurrent infusion provides an indirect
measure of the exact drug distribution. In this study, we propose using
microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a
drug-carrying vehicle to directly monitor the infused drug. Results show that
microbubbles can provide excellent detectability through MRI relaxometry and
accurately represent drug distribution during CED infusion. Compared with the
short half-life of Gd-DTPA (1-2 hours), microbubbles allow an extended
observation period of up to 12 hours. Moreover, microbubbles provide a
sufficiently high drug payload, and glioma mice that underwent a CED infusion of
microbubbles carrying doxorubicin presented considerable tumor growth suppression
and a significantly improved survival rate. This study recommends microbubbles as
a new theranostic tool for CED procedures.
PMID- 28418847
TI - Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT
expression and MPF activity.
AB - If no fertilization occurs at an appropriate time after ovulation, oocyte quality
deteriorates rapidly as a process called postovulatory aging. Because the
postovulatory aging of oocytes has detrimental effects on embryo development and
offspring, many efforts have been made to prevent oocyte aging. Here we showed
that quercetin prevented the decline in oocyte quality during postovulatory aging
of oocytes. Quercetin treatment reduced aging-induced morphological changes and
reactive oxygen species accumulation. Moreover, quercetin attenuated the aging
associated abnormalities in spindle organization and mitochondrial distribution,
preventing decrease of SIRT expression and histone methylation. Quercetin also
ameliorated the decrease in maturation-promoting factor activity and the onset of
apoptosis during postovulatory aging. Furthermore, quercetin treatment during
postovulatory aging improves early embryo development. Our results demonstrate
that quercetin relieves deterioration in oocyte quality and improves subsequent
embryo development.
PMID- 28418849
TI - Oncologic and obstetrical outcomes with fertility-sparing treatment of cervical
cancer: a systematic review and meta-analysis.
AB - OBJECTIVE: The objectives of this study were to evaluate the rates of recurrence,
survival and pregnancy, and characterize pregnancy outcomes of early-stage
cervical cancer(eCC) treated with fertility-sparing methods such as cervical
conization (CON) and radical trachelectomy(RT) with or without pelvic
lymphadenectomy. STUDY DESIGN: This was a meta-analysis of observational studies
analyzed by a random-effects model and a meta-regression to assess heterogeneity.
RESULTS: Sixty observational studies encompassing 2,854 patients were included;
17 of which evaluated CON and 43 RT. Three hundred and seventy-five patients were
included in the CON group: 176(46.9%) stage IA1 and 167(44.5%) stage IB1. In the
RT group, 2479 cases were included: 143(6.0%) stage IA1, 299(12.1%) stage IA2,
1987(79.9%) stage IB1. CON was performed in 347(92.5%) cases, resulting in a
recurrence rate of 0.4%(95%CI: 0.0%-1.4%), a death rate of 0%(0%-0%), a pregnancy
rate of 36.1%(26.4%-46.2%), a spontaneous abortion rate of 14.8%(9.3%-21.2%) and
a preterm delivery rate of 6.8%(1.5%-15.5%). For the RT group, 2273(91.7%)
underwent successful surgeries with a recurrence rate of 2.3%(1.3%-3.4%),a death
rate of 0.7%(0.3%-1.1%), a pregnancy rate of 20.5%(16.8%-24.5%), a spontaneous
abortion rate of 24.0%(18.8%-29.6%) and a preterm delivery rate of 26.6%(19.6%
34.2%). From a subgroup analysis, the recurrence rates for stage IA tumors
treated with CON and RT were 0.4%(0.0%-1.9%) and 0.7%(0.0%-2.3%), respectively;
and for stage IB were 0.6%(0.0%-2.7%) and 2.3%(0.9%-4.1%). CONCLUSION: Fertility
sparing treatment including CON or RT for eCC is feasible and carefully selected
women can preserve fertility and achieve pregnancy resulting in live births. CON
seems to result in better pregnancy outcomes than RT with similar rates of
recurrence and mortality.
PMID- 28418851
TI - High serum lactate dehydrogenase predicts an unfavorable outcome in Chinese
elderly patients with multiple myeloma.
AB - There is significant heterogeneity among multiple myeloma (MM) patients with the
survival duration varying greatly from a few months to several years. This study
retrospectively analyzed serum lactate dehydrogenase (LDH) in 105 cases of newly
diagnosed elderly MM patients to investigate its value for outcome prediction.
Serum LDH concentrations were evaluated prior to induction therapy. Prognostic
analyses were carried out based on LDH levels and patients' other clinical data.
We also applied the recently proposed Revised International Staging System (R
ISS) to 70 patients with the available data. Of all the patients, elevated serum
LDH levels (>=271U/L) were observed in 13.3% (14 out of 105) patients at
diagnosis. Compared with normal LDH group, high LDH group had significantly
shorter overall survival (OS) (15.5 vs. 52.5 months, p = 0.002) and median
progression free survival (PFS) (12.0 vs. 24 months, p = 0.030), as well as 2
year OS rate (20% vs. 81%, p < 0.001) and PFS rate (22% vs. 44%, p = 0.005). A
multivariate analysis identified high LDH as a unique independent adverse
prognostic parameter for both OS and PFS. In addition, there were significant
differences between R-ISS II and R-ISS III patients in both median OS (52.5 vs.
15.5 months, p < 0.001) and PFS (23 vs. 7.5 months, p = 0.004). Furthermore, high
LDH was a unique independent adverse indicator for overall response rate (ORR)
and early death in elderly MM patients. These results identified LDH as an
unfavorable prediction for the outcome of Chinese elderly patients with MM. R-ISS
based on LDH is superior to ISS in prognostic assessment.
PMID- 28418852
TI - Structural homologies between phenformin, lipitor and gleevec aim the same
metabolic oncotarget in leukemia and melanoma.
AB - Phenformin's recently demonstrated efficacy in melanoma and Gleevec's
demonstrated anti-proliferative action in chronic myeloid leukemia may lie within
these drugs' significant pharmacokinetics, pharmacodynamics and structural
homologies, which are reviewed herein. Gleevec's success in turning a fatal
leukemia into a manageable chronic disease has been trumpeted in medical,
economic, political and social circles because it is considered the first
successful targeted therapy. Investments have been immense in omics analyses and
while in some cases they greatly helped the management of patients, in others
targeted therapies failed to achieve clinically stable recurrence-free disease
course or to substantially extend survival. Nevertheless protein kinase
controlling approaches have persisted despite early warnings that the targeted
genomics narrative is overblown. Experimental and clinical observations with
Phenformin suggest an alternative explanation for Gleevec's mode of action. Using
13C-guided precise flux measurements, a comparative multiple cell line study
demonstrated the drug's downstream impact on submolecular fatty acid processing
metabolic events that occurred independent of Gleevec's molecular target.
Clinical observations that hyperlipidemia and diabetes are both reversed in mice
and in patients taking Gleevec support the drugs' primary metabolic targets by
biguanides and statins. This is evident by structural data demonstrating that
Gleevec shows pyridine- and phenyl-guanidine homology with Phenformin and
identical phenylcarbamoyl structural and ligand binding homology with Lipitor.
The misunderstood mechanism of action of Gleevec is emblematic of the pervasive
flawed reasoning that genomic analysis will lead to targeted, personalized
diagnosis and therapy. The alternative perspective for Gleevec's mode of action
may turn oncotargets towards metabolic channel reaction architectures in leukemia
and melanoma, as well as in other cancers.
PMID- 28418854
TI - Association between the BRCA2 rs144848 polymorphism and cancer susceptibility: a
meta-analysis.
AB - The BRCA2 gene plays an important role in cancer carcinogenesis, and
polymorphisms in this gene have been associated with cancer risk. The BRCA2
rs144848 polymorphism has been associated with several cancers, but results have
been inconsistent. In the present study, a meta-analysis was performed to assess
the association between the rs144848 polymorphism and cancer risk. Literature was
searched from the databases of PubMed, Embase and Google Scholar before April
2016. The fixed or random effects model was used to calculate pooled odd ratios
on the basis of heterogeneity. Meta-regression, sensitivity analysis, subgroup
analysis and publication bias assessment were also performed using STATA 11.0
software according to Preferred Reporting Items for Systematic Reviews and Meta
Analyses 2009. A total of 40 relevant studies from 30 publications including
34,911 cases and 48,329 controls were included in the final meta-analysis. Among
them, 22 studies focused on breast cancer, seven on ovarian cancer, five on non
Hodgkin lymphoma, and the remaining six studies examined various other cancers.
The meta-analysis results showed that there were significant associations between
the rs144848 polymorphism and cancer risk in all genetic models. Stratified by
cancer type, the rs144848 polymorphism was associated with non-Hodgkin lymphoma.
Stratified by study design, the allele model was associated with breast cancer
risk in population-based studies. The meta-analysis suggests that the BRCA2
rs144848 polymorphism may play a role in cancer risk. Further well-designed
studies are warranted to confirm these results.
PMID- 28418855
TI - A review and outlook in the treatment of osteosarcoma and other deep tumors with
photodynamic therapy: from basic to deep.
AB - Photodynamic therapy, one of the most promising minimally invasive treatments,
has received increasing focus in tumor therapy research, which has been widely
applied in treating superficial tumors. Three basic factors - photosensitizer,
the light source, and oxidative stress - are responsible for tumor cell
cytotoxicity. However, due to insufficient luminous flux and peripheral tissue
damage, the utilization of photodynamic therapy is facing a huge limitation in
deep tumor therapy. Osteosarcoma is the typical deep tumor, which is the most
commonly occurring malignancy in children and adolescents. Despite developments
in surgery, high risks of the amputation still threatens the health of
osteosarcoma patients. In this review, we summarize recent developments in the
field of photodynamic therapy and specifically PDT research in OS treatment
modalities. In addition, we also provide some novel suggestions, which could
potentially be a breakthrough in PDT-induced OS therapies. PDT has the potential
to become an effective therapy while the its limitations still present when
applied on the treatment of OS or other types of deep tumors. Thus, more
researches and studies in the field are required.
PMID- 28418856
TI - Low-density lipoprotein receptor-related protein 6 is a novel coreceptor of
protease-activated receptor-2 in the dynamics of cancer-associated beta-catenin
stabilization.
AB - Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the
molecular machinery of PAR2-instigated tumors remains to be elucidated. We show
that PAR2 is a potent inducer of beta-catenin stabilization, a core process in
cancer biology, leading to its transcriptional activity. Novel association of low
density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds
(Fz), with PAR2 takes place following PAR2 activation. The association between
PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence
resonance energy transfer (BRET), and confocal microscopy analysis. The
association was further supported by ZDOCK protein-protein server. PAR2-LRP6
interaction promotes rapid phosphorylation of LRP6, which results in the
recruitment of Axin. Confocal microscopy of PAR2-driven mammary gland tumors in
vivo, as well as in vitro confirms the association between PAR2 and LRP6. Indeed,
shRNA silencing of LRP6 potently inhibits PAR2-induced beta-catenin
stabilization, demonstrating its critical role in the induced path. We have
previously shown a novel link between protease-activated receptor-1 (PAR1) and
beta-catenin stabilization, both in a transgenic (tg) mouse model with
overexpression of human PAR1 (hPar1) in the mammary glands, and in cancer
epithelial cell lines. Unlike in PAR1-Galpha13 axis, both Galpha12 and Galpha13
are equally involved in PAR2-induced beta-catenin stabilization. Disheveled (DVL)
is translocated to the cell nucleus through the DVL-PDZ domain. Collectively, our
data demonstrate a novel PAR2-LRP6-Axin interaction as a key axis of PAR2-induced
beta-catenin stabilization in cancer. This newly described axis enhances our
understanding of cancer biology, and opens new avenues for future development of
anti-cancer therapies.
PMID- 28418857
TI - Multi-factorial modulation of colorectal carcinoma cells motility - partial
coordination by the tetraspanin Co-029/tspan8.
AB - Colorectal carcinoma cells Isreco1 display an ability to migrate controlled by a
complex set of signals issued from the membrane. By comparing cells infected by
mycoplasmas and mycoplasmas free cells, we have established that basal 2D
migration is dependent on a double signal mediated by the collagen receptors
integrins alpha1/2 and the Toll-Like receptor TLR2. The signal issued from
mycoplasmas can be replaced by a TLR2 ligand and the functional effect is
neutralized by silencing of MyD88. Following previous observation that
downregulation of E-cadherin/p120 catenin increases cell motility, we now report
that EGFR or CD44 inhibition have a similar effect on cell motility that is
restricted to tetraspanin Co-029/tspan8 transduced IsrecoI cells (Is1-Co029). The
modulation of cell migration linked to EGFR or CD44 can be neutralized by
antagonizing Co-029 with the mAb Ts29.1 or by RNA interference. Altogether these
data point to a crucial role of Co-029 in the modulation of colon cancer cell
motility which could be related to the protumoral effect reported for this
tetraspanin. Among surface molecules able to mediate Co-029 function, E-cadherin,
EGFR and CD44 appear as likely candidates.
PMID- 28418858
TI - The miR-124-p63 feedback loop modulates colorectal cancer growth.
AB - Among the diverse co-regulatory relationships between transcription factors (TFs)
and microRNAs (miRNAs), feedback loops have received the most extensive research
attention. The co-regulation of TFs and miRNAs plays an important role in
colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two
isoforms of p63, TAp63 and DeltaNp63, via iASPP, while p63 modulates signal
transducers and activators of transcription 1 (STAT1) expression by targeting miR
155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124.
Taken together, these results reveal a feedback loop between miRNAs and TFs. This
feedback loop comprises miR-124, iASPP, STAT1, miR-155, TAp63 and DeltaNp63,
which are essential for CRC growth. Moreover, this feedback loop is perturbed in
human colon carcinomas, which suggests that the manipulation of this microRNA-TF
feedback loop has therapeutic potential for CRC.
PMID- 28418859
TI - Serum metabolomics differentiating pancreatic cancer from new-onset diabetes.
AB - To establish a screening strategy for pancreatic cancer (PC) based on new-onset
diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the
metabolic pathways associated with PC related DM were performed. Serum samples
from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM
were examined by liquid chromatography-mass spectrometry. Data were analyzed
using principal components analysis (PCA) and orthogonal projection to latent
structures (OPLS) of the most significant metabolites. The diagnostic model was
constructed using logistic regression analysis. Metabolic pathways were analyzed
using the web-based tool MetPA. PC patients with NO-DM were older and had a lower
BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of
patients with PC and NO-DM were significantly different from those of patients
with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were
identified by the OPLS model. The logistic regression model using a panel of two
metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high
sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic
pathways associated with PC related DM were valine, leucine and isoleucine
biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid
metabolism. In conclusion, screening for PC based on NO-DM using serum
metabolomics in combination with clinic characteristics and CA19-9 is a potential
useful strategy. Several metabolic pathways differed between PC related DM and
type 2 DM.
PMID- 28418860
TI - Targeting the overexpressed ROC1 induces G2 cell cycle arrest and apoptosis in
esophageal cancer cells.
AB - Recent reports showed that regulator of Cullins-1 (ROC1) play an important role
in tumor progression in a tumor-specific manner. However, the role and mechanism
of ROC1 in esophageal cancer remains elusive. Here we demonstrated that ROC1 was
overexpressed in esophageal squamous cell carcinomas, which was positive
associated with poor prognosis of esophageal cancer patients. ROC1 knockdown
significantly inhibited the growth of esophageal cancer cells in vitro and in
vivo. Mechanistically, ROC1 silencing induced G2 cell cycle arrest and triggered
apoptosis by accumulating the pro-apoptotic protein NOXA. Consistently, the
downregulation of NOXA expression via siRNA substantially attenuated apoptosis
induced by ROC1 silencing. These findings suggest that ROC1 is an appealing drug
target for esophageal cancer.
PMID- 28418861
TI - Brain-derived neurotrophic factor involved epigenetic repression of UGT2B7 in
colorectal carcinoma: A mechanism to alter morphine glucuronidation in tumor.
AB - Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug
enzymes, is responsible on the glucuronidation of abundant endobiotics or
xenobiotics. We here report that it is markedly repressed in the tumor tissues of
colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will
stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance
generation by activating the positive signals in histone 3, especially for
trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac). Further
study reveals that brain-derived neutrophilic factor (BDNF), a secretory
neurotrophin, enriched in CRC can interact and inhibit UGT2B7 by primarily
blocking the positive signals of H3K4Me3 as well as activating H3K27Ac on the
promoter region of UGT2B7. Meanwhile, BDNF repression attributes to the
sensitizations of main core factors in poly-comb repressive complex (PRC) 1
rather than PRC2 as the reason of the depression of SUZ12 in the later complex.
Besides that, the productions of two main morphine glucuronides are both
increased in the BDNF deficient or TSA and BIX-01294 treated morphine tolerance
like HCT-116 cells. On the same condition, active metabolite, morphine-6
glucuronide (M6G) was accumulated more than inactive M3G. Our findings imply that
enzymatic activity enhancement and substrate regioselective catalysis alteration
of UGT2B7 may release morphine tolerance under the cure of tumor-induced pain.
PMID- 28418862
TI - Niclosamide is a potential therapeutic for familial adenomatosis polyposis by
disrupting Axin-GSK3 interaction.
AB - The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and
cancer progression, and canonical Wnt signaling tightly controls Snail, a key
transcriptional repressor of EMT. While the suppression of canonical Wnt
signaling and EMT comprises an attractive therapeutic strategy, molecular targets
for small molecules reverting Wnt and EMT have not been widely studied.
Meanwhile, the anti-helminthic niclosamide has been identified as a potent
inhibitor of many oncogenic signaling pathways although its molecular targets
have not yet been clearly identified. In this study, we show that niclosamide
directly targets Axin-GSK3 interaction, at least in part, resulting in
suppression of Wnt/Snail-mediated EMT. In vitro and in vivo, disruption of Axin
GSK3 complex by niclosamide induces mesenchymal to epithelial reversion at nM
concentrations, accompanied with suppression of the tumorigenic potential of
colon cancer. Niclosamide treatment successfully attenuates Snail abundance while
increasing E-cadherin abundance in xenograft tumor. Notably, oral administration
of niclosamide significantly suppressed adenoma formation in an APC-MIN mice
model, indicating that niclosamide is an effective therapeutic for familial
adenomatosis polyposis (FAP) patients. In this study, we identified a novel
target to control the canonical Wnt pathway and Snail-mediated EMT program, and
discovered a repositioned therapeutics for FAP patients.
PMID- 28418863
TI - GALNT14 genotype as a response predictor for concurrent chemoradiotherapy in
advanced esophageal squamous cell carcinoma.
AB - Esophageal squamous cell carcinoma is an aggressive cancer. We investigated
genetic response predictors for patients with advanced esophageal squamous cell
carcinoma receiving concurrent chemoradiotherapy. A cohort of 108 patients was
recruited. Survival analysis showed that lower esophageal location of tumor, more
advanced metastasis stage, and longer length of tumor were associated with poorer
overall survival (adjusted P = 0.001, < 0.001, and 0.045, respectively), while
the presence of complete/partial response to concurrent chemoradiotherapy was
independently associated with better overall survival (adjusted P < 0.001). The
GALNT14-rs9679162 "GG" genotype was associated with a lower rate of response (P =
0.014). Multivariate Cox-proportional hazards models also showed that the "GG"
genotype was associated with a longer time to complete/partial response (adjusted
P = 0.022), independent of leukocyte counts and gender. In conclusion, the
presence of a complete/partial response to chemoradiotherapy was critical for
advanced esophageal squamous cell carcinoma patients to achieve better overall
survival. The GALNT14-rs9679162 "GG" genotype was associated with a longer time
to complete/partial response of concurrent chemoradiotherapy.
PMID- 28418864
TI - Bone marrow-derived mesenchymal stem cells overexpressing MiR-21 efficiently
repair myocardial damage in rats.
AB - OBJECTIVE: We investigated the ability of bone marrow derived mesenchymal stem
cells (BMSCs) overexpressing microRNA-21 (miR-21) to repair cardiac damage
induced by anthracyclines in rats. METHODS: Sprague-Dawley (SD) rats of 2~3 weeks
old were selected to isolate and culture BMSCs. A lentivirus harboring pLVX-miR
21 was generated and transfected into rat BMSCs. The rats were assigned into an
untreated negative control group, and groups injected with adriamycin alone or
with adriamycin followed by BMSCs, pLVX-BMSCs or pLVX-miR-21-BMSCs (n = 10 each).
Proliferation and migration of cells were detected by cholecystokinin-8 (CCK- 8)
and transwell. MiR-21 expression, mRNA expressions of B cell lymphoma 2 (Bcl2),
BAX (BCL-2-associated X protein) and vascular endothelial growth factor (VEGF)
were tested by qRT-PCR. Western blotting was applied to detect protein
expressions of Bcl-2, Bax and VEGF. RESULTS: Using CCK- 8 and transwell assays,
we found that pLVX-miR-21-BMSCs, which overexpressed miR-21, exhibited greater
proliferation and migration than untransfected BMSCs or pLVX-BMSCs. Ultrasonic
cardiograms and immunohistochemical analysis demonstrated that among the five
groups, the pLVX-miR-21-BMSC group exhibited the most improved heart function and
enhanced angiogenesis. Moreover, the pLVX-miR-21-BMSC group showed enhanced
expression of Bcl-2, VEGF and Cx43 and reduced expression of Bax, BNP and
troponin T. CONCLUSION: These findings suggest miR-21 overexpression enhanced the
proliferation, invasiveness and differentiation of BMSCs as well as expression of
key factors (Bcl-2, VEGF and Bax) essential for repairing the cardiac damage
induced by anthracyclines and restoring heart function.
PMID- 28418865
TI - Anti-helminthic niclosamide inhibits Ras-driven oncogenic transformation via
activation of GSK-3.
AB - Despite the importance of Ras oncogenes as a therapeutic target in human cancer,
their 'undruggable' tertiary structures limit the effectiveness of anti-Ras
drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase
kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent
degradation. In the accompanying report, we show that the anti-helminthic
niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer
cells, with reversion of Snail-mediated epithelial-mesenchymal transition. In
this study, we report that niclosamide effectively suppresses Ras and nuclear
NFAT activities regardless of the mutational status of Ras at nM levels.
Mechanistically, niclosamide increased endogenous GSK-3 activity, shortening the
half-life of mutant Ras. Further, niclosamide activates Raf-1 kinase inhibitory
protein, a downstream target of Snail repressor. Niclosamide treatment attenuates
Ras-induced oncogenic potential in vitro and in vivo. These findings provide a
clinically available repositioned Ras inhibitor as well as a novel strategy for
inhibiting the Ras via GSK-3.
PMID- 28418866
TI - Investigation of hypoxia conditions using oxygen-enhanced magnetic resonance
imaging measurements in glioma models.
AB - The objective of this study was to determine whether using oxygen-enhanced
magnetic resonance imaging (OE-MRI) to assess hypoxia is feasible and whether
historical measurements, pO2 changes, and percentage of signal intensity changes
(PSIC) are correlated in an animal model of glioma. A total of 25 Sprague-Dawley
rats were used to establish C6 brain or subcutaneous glioma model. Nine rats with
brain gliomas underwent OE-MRI followed by histopathologic analysis to assess
microvessel density and hypoxia. Another 11 rats were underwent OE-MRI and were
followed for a survival analysis. Time-T1-weighted MR signal intensity (SI)
curves and PSIC maps were derived from the OE-MRI data. High-regions of interests
(ROI-h; PSIC > 10%) and low-ROIs (ROI-l; PSIC < 10%) were defined on the PSIC
maps. To validate the PSIC map for identifying tumor hypoxia, we subjected an
additional 5 rats with subcutaneous glioma to OE-MRI and pO2 measurements. All
tumors showed regional heterogeneity on the PSIC maps. For the brain tumors, the
time-SI curves for the ROIs-h showed a greater increase in SI than those for the
ROIs-l did. The percentage of tumor area with a low PSIC was significantly
correlated with the percentage of hypoxia staining and necrosis (r =0.71;
P<0.05). ROIs with a higher PSIC typically had more vessels (r=0.88; P<0.05). A
significant difference in survival was shown (log-rank P = 0.035). The time-pO2
curves of the subcutaneous tumors were similar to the time-SI curves. PSIC was
significantly correlated with pO2 changes (r =0.82; P<0.05). These findings
suggest that OE-MRI measurements can be used to assess hypoxia in C6 glioma
models. In these models, the PSIC value was correlated with survival, indicating
that PSIC could serve as a prognostic marker for glioma.
PMID- 28418868
TI - GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and
its expression is associated with poorer prognosis.
AB - Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub
population of cancer cells that are endowed with higher tumor-initiating ability,
self-renewal ability and differentiation ability. CSCs/CICs could be isolated as
high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer
samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh
cells and investigated the molecular aspects. ALDH1high cells showed greater
sphere-forming ability and higher tumor-initiating ability in immune-deficient
mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in
ALDH1high cells. cDNA microarray analysis revealed that an ionotropic glutamate
receptor glutamate receptor, ionotropic, kainate 2 (GRIK2) was expressed in
ALDH1high cells at a higher level than that in ALDH1low cells. GRIK2 gene
knockdown by siRNAs decreased the sphere-forming ability and invasion ability,
whereas GRIK2 overexpression increased the sphere-forming ability, invasion
ability and tumorigenicity, indicating that GRIK2 has a role in the maintenance
of CSCs/CICs. Immunohistochemical staining revealed that higher levels of GRIK2
and ALDH1 expression were related to poorer prognosis in urinary tract carcinoma
cases. The findings indicate that GRIK2 has a role in the maintenance of
urothelial CSCs/CICs and that GRIK2 and ALDH1 can be prognosis prediction markers
for urinary tract carcinomas.
PMID- 28418867
TI - Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1,
CLIP4 and MSC DNA methylation in endoscopic biopsies.
AB - Clinically useful molecular tools to triage gastric cancer patients are not
currently available. We aimed to develop a molecular tool to predict gastric
cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer
clinics in low resource settings.We discovered and validated a DNA methylation
biomarker panel in endoscopic samples obtained from 362 patients seen between
2004 and 2009 in three high-risk gastric cancer clinics in Lima, Peru, and
validated it in 306 samples from the Cancer Genome Atlas project ("TCGA").
Global, epigenome wide and gene-specific DNA methylation analyses were used in a
Phase I Biomarker Development Trial to identify a continuous biomarker panel that
combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation
levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between
the GDMI and histological progression to gastric cancer, when comparing gastritis
patients without metaplasia (mean = 5.74, 95% CI, 4.97-6.50), gastritis patients
with metaplasia (mean = 4.81, 95% CI, 3.77-5.84), and gastric cancer cases (mean
= 3.38, 95% CI, 2.82-3.94), respectively (p < 0.0001). Promoter methylation of
IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001),
is also associated with increasing severity from gastritis with no metaplasia to
gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4,
ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful
molecular tools for gastric cancer risk stratification in endoscopic biopsies.
PMID- 28418869
TI - Development of a Taiwan cancer-related fatigue cognition questionnaire:
reliability and validity.
AB - PURPOSE: We prospectively designed a Taiwan cancer-related fatigue cognition
questionnaire, version 1.0 (TCRFCQ-V1.0), for Taiwanese patients with cancer and
investigated the reliability and validity of this questionnaire. RESULTS: The
completion rate of the TCRFCQ-V1.0 was high (97% of the patients completed all
items), and the rate of missing data was low (0.2%-1.1% for each item). Moreover,
the Cronbach alpha value was 0.889. We eliminated 5 items because their
respective Cronbach alpha values were higher than the total mean value of
Cronbach's alpha. Overall, the TCRFCQ-V1.0 had adequate Cronbach alpha
coefficients (range, from 0.882 to 0.889). In addition, the results of Bartlett's
test were significant (chi-squared, 2390.11; p < 0.001), indicating the
appropriateness of factor analysis. Sampling adequacy was confirmed by the Kaiser
Meyer-Olkin statistic of 0.868. Through exploratory factor analysis, we
identified 6 factors with eigenvalues of > 1, and the scree plot indicated no
flattening factors. Overall, 28 items achieved a factor loading of >= 0.55.
MATERIALS AND METHODS: We enrolled patients with cancer who were aged > 18 years,
had received a pathological diagnosis of cancer, and had undergone cancer
treatments such as surgery, chemotherapy, radiotherapy, or concurrent
chemoradiotherapy at a single institute in Taiwan. Of the identified 167 eligible
patients, 161 (96.4%) were approached. Of these patients, 6 (7.2%) declined to
participate and 155 (92.8%) were interviewed. The initial 43 items in the TCRFCQ
V1.0 were assessed for ceiling and floor effects. CONCLUSIONS: The TCRFCQ-V1.0 is
a reliable and valid instrument for measuring CRF cognition in Taiwanese patients
with cancer.
PMID- 28418872
TI - Overexpression of Fli-1 in astrocytoma is associated with poor prognosis.
AB - BACKGROUND: Astrocytoma, a common and highly malignant type of brain tumor, is
associated with poor overall survival despite advances in surgical treatment,
radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been
shown to increase cellular proliferation and tumorigenesis in many types of
cancer; however, previous reports have not described a correlation between
clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to
elucidate the clinical role of Fli-1 in astrocytoma. RESULTS: High-level of Fli-1
protein expression was significantly association with World Health Organization
(WHO) high grade and poor prognosis. A multivariate analysis revealed that the
WHO grade and Fli-1 protein expression were independent factor of prognostic
factors of patients with astrocytoma. In addition, Fli-1 silencing inhibited
proliferation, migration, and invasion and led to the downregulation of Ki-67,
VEGF, and cyclin D1 expression in the astrocytoma cells. MATERIALS AND METHODS:
Fli-1 protein expression in astrocytoma tissue samples were detected via
immunohistochemistry, and potential correlations between clinical parameters and
Fli-1 expression were assessed in patients with astrocytoma. Additionally,
proliferation, invasion, and migration assays of astrocytoma cell lines were
conducted to evaluate the effects of short interfering RNA (siRNA) on these
processes; in addition, these cells were subjected to western blotting to detect
the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1. CONCLUSION: Fli-1
shows promise as a potential prognostic biomarker and therapeutic molecular
target for astrocytoma patients.
PMID- 28418870
TI - Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal
cancers: a systematic review and meta-analysis.
AB - An accurate, time efficient, and inexpensive prognostic indicator is needed to
reduce cost and assist with clinical decision making for cancer management. The
neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing,
has been explored in a variety of cancers. We sought to determine its prognostic
value in gastrointestinal cancers and performed a meta-analysis of published
studies using the Meta-analysis Of Observational Studies in Epidemiology
guidelines. Included were randomized control trials and observational studies
that analyzed humans with gastrointestinal cancers that included NLR and hazard
ratios (HR) with overall survival (OS), disease-free survival (DFS), progression
free survival (PFS), and/or cancer-specific survival (CSS).We analyzed 144
studies comprising 45,905 patients, two-thirds of which were published after
2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate
models were 3.4, 3.0, 5.0 (+/-IQR 2.5-5.0), respectively. Overall, NLR greater
than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P <
0.001). This association was observed in all subgroups based on tumor site,
stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70
(95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83
(95% CI, 1.50-2.23, P < 0.001), respectively.Available evidence suggests that NLR
greater than the cutoff reduces OS, independent of geographic location,
gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS
also have worse outcomes with elevated NLR.
PMID- 28418873
TI - Combined inhibition of GLI and FLT3 signaling leads to effective anti-leukemic
effects in human acute myeloid leukemia.
AB - Activation of the Hedgehog pathway has been implicated in the pathogenesis of
several tumor types including myeloid leukemia. Previously we demonstrated that
overexpression of Hedgehog downstream mediators GLI1/2 confers an adverse
prognosis to patients with acute myeloid leukemia (AML) and is correlated with a
FLT3 mutated status. To analyze a possible non-canonical activation of the
Hedgehog pathway via FLT3 and PI3K, we performed blocking experiments utilizing
inhibitors for FLT3 (sunitinib), PI3K (PF-04691502) and GLI1/2 (GANT61) in FLT3
mutated and FLT3 wildtype AML cell lines and primary blasts. Combination of all
three compounds had stronger anti-leukemic effects in FLT3-mutated compared to
FLT3 wildtype AML cells in vitro. Interestingly, the colony growth of normal
CD34+ cells from healthy donors was not impeded by the triple inhibitor
combination possibly opening a therapeutic window for the clinical use of
inhibitor combinations. Besides, combined treatment with sunitinib, PF-04691502
and GANT61 significantly prolonged the survival of mice transplanted with FLT3
mutated MV4-11 cells compared to the single agent treatments. Furthermore, the
inhibition of FLT3 and PI3K resulted in reduced GLI protein expression and
promotor activity in FLT3-mutated but not in FLT3 wildtype AML cell lines in
western blotting and GLI1/2 promoter assays supporting our hypothesis of non
canonical GLI activation via FLT3.In summary, FLT3-mutated in contrast to FLT3
wildtype cells or normal human hematopoietic progenitor cells are exquisitely
sensitive to combined inhibition by FLT3, PI3K and GLI1/2 overcoming some of the
limitations of current FLT3 directed therapy in AML. The development of GLI1/2
inhibitors is highly desirable.
PMID- 28418874
TI - Is there a prognostic value of tumor location among Chinese patients with
colorectal cancer?
AB - Differences in epidemiology, pathological features, and molecular pathogeneses
have been observed according to primary tumor location in colorectal cancer
(CRC). However, predicting CRC survival by tumor location remains controversial.
Therefore, we compared the pathological characteristics, molecular features, and
prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC), and
rectal cancer (RECC) among Chinese patients with CRC. We evaluated 4,426 patients
with stage I-III CRC between January 2008 and July 2014from Fudan University
Shanghai Cancer Center. All patients were grouped by the locations of tumors
(RCC, LCC, and RECC). Patients with RCC were more likely to be women and older,
have poorly differentiated tumors, microsatellite repair deficiency (dMMR),
negative p53 expression, and the mucinous subtype. Unadjusted Kaplan-Meier
survival curves revealed survival in RCC than in LCC and RECC. However, there
were no significant differences in OS and DFS between LCC and RECC. The same
results were observed for each disease stage. Unadjusted models revealed an
increased risk of mortality, recurrence, or metastasis for RCC (OS: HR, 1.68,
P=0.0002 and DFS: HR, 1.24, P=0.032), compared to LCC (all stages), and a similar
result was observed for stage III patients (OS: HR, 1.79, P<0.0001 and DFS: HR,
1.33, P=0.021). However, adjusted Cox proportional hazard regression models
revealed no significant differences in survival between the three tumor
locations. Tumor location was not an independent prognostic factor among Chinese
patients with stage I-III CRC. But RCCs had a worse prognosis in the dMMR
subgroup. The related mechanism remains to be investigated.
PMID- 28418876
TI - PPARGC1A rs3736265 G>A polymorphism is associated with decreased risk of type 2
diabetes mellitus and fasting plasma glucose level.
AB - It has been reported that peroxisome proliferator-activated receptor gamma
(PPARG) and peroxisome proliferator-activated receptor gamma co-activator 1
(PPARGC1) family (e.g. PPARGC1A and PPARGC1B) are key agents in the development
and pathophysiology of type 2 diabetes mellitus (T2DM). In this study, we
designed a case-control study and selected PPARG rs1801282 C>G, PPARG rs3856806
C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A,
PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms to assess the
relationship between these polymorphisms and T2DM using the SNPscan method. A
total of 502 T2DM patients and 784 non-diabetic controls were enrolled. We found
that PPARGC1A rs3736265 G>A polymorphism was correlated with a borderline
decreased susceptibility of T2DM. In a subgroup analysis by age, sex, alcohol
use, smoking status and body mass index, a significantly decreased risk of T2DM
in <65 years and female groups was found. Haplotype comparison analysis indicated
that CTTCGGG and CTCTGGG haplotypes with the order of PPARG rs1801282 C>G, PPARG
rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265
G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms in gene
position significantly increased the risk of T2DM. However, CCCCACA haplotype
conferred a decreased risk to T2DM. We also found that PPARGC1A rs3736265 A
allele decreased the level of fasting plasma glucose (FPG), while increased the
level of Triglyceride. In conclusion, Our findings suggest that variants of
PPARGC1A rs3736265 G>A polymorphism decrease the level of FPG, improving the
expectation of study in individual's prevention strategies to T2DM.
PMID- 28418877
TI - Transforming growth factor-beta1 promotes breast cancer metastasis by
downregulating miR-196a-3p expression.
AB - Transforming growth factor-beta1 is considered a key contributor to the
progression of breast cancer. MicroRNAs are important factors in the development
and progression of many malignancies. In the present study, upon studies of
breast cancer cell lines and tissues, we showed that microRNA -196a-3p is
decreased by transforming growth factor-beta1 in breast cancer cells and
associated with breast cancer progression. We identified neuropilin-2 as a target
gene of microRNA -196a-3p and showed that it is regulated by transforming growth
factor-beta1. Moreover, transforming growth factor-beta1-mediated inhibition of
microRNA -196a-3p and activation of neuropilin-2were required for transforming
growth factor-beta1-induced migration and invasion of breast cancer cells. In
addition, neuropilin-2 expression was suppressed in breast tumors, particularly
in triple-negative breast cancers. Collectively, our findings strongly indicate
that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and
patient survival and a potential therapeutic target in metastatic breast cancer.
PMID- 28418879
TI - Transcriptome profiling reveals miR-9-3p as a novel tumor suppressor in gastric
cancer.
AB - It has been well established that microRNAs (miRNAs) play important roles in
biological processes. To comprehensively measure the altered miRNA expression, we
presented the miRNA expression profile of gastric cancer using microarray. We
identified 33 miRNAs that were significantly differentially regulated in gastric
specimens compared to adjacent normal tissues, among which miR-9-3p expression
are significantly down-regulated in gastric cancers. Next, a cohort of 100
gastric cancer tissues and matched normal tissues were enrolled. Kaplan-Meier and
multivariate Cox survival analyses were applied to evaluate the prognostic value
of miR-9-3p expression, and the result showed that patients with lower miR-9-3p
expression level have significantly poorer overall survival. The expression level
of miR-9-3p has been proved to be an independent prognostic factor for 5-year
overall survival. Furthermore, the result indicated that over-expression of miR-9
3p can inhibit gastric cancer cell invasion. Taken together, our results
suggested that miR-9-3p plays important role in tumor invasion, and these
findings implicated the potential effects of miR-9-3p on prognosis of gastric
cancer.
PMID- 28418878
TI - The TERT rs2736100 polymorphism increases cancer risk: A meta-analysis.
AB - Abnormal telomerase activity is implicated in cancer initiation and development.
The rs2736100 T > G polymorphism in the telomerase reverse transcriptase (TERT)
gene, which encodes the telomerase catalytic subunit, has been associated with
increased cancer risk. We conducted a meta-analysis to more precisely assess this
association. After a comprehensive literature search of the PubMed and EMBASE
databases up to November 1, 2016, 61 articles with 72 studies comprising 108,248
cases and 161,472 controls were included in our meta-analysis. Studies were
conducted on various cancer types. The TERT rs2736100 polymorphism was associated
with increased overall cancer risk in five genetic models [homozygous model (GG
vs. TT): odds ratio (OR) = 1.39, 95% confidence interval (95% CI) = 1.26-1.54, P
< 0.001; heterozygous model (TG vs. TT): OR = 1.16, 95% CI = 1.11-1.23, P <
0.001; dominant model (TG + GG vs. TT): OR = 1.23, 95% CI = 1.15-1.31, P < 0.001;
recessive model (GG vs. TG + TT): OR = 1.25, 95% CI = 1.16-1.35, P < 0.001; and
allele contrast model (G vs. T): OR = 1.17, 95% CI = 1.12-1.23, P < 0.001]. A
stratified analysis based on cancer type associated the polymorphism with
elevated risk of thyroid cancer, bladder cancer, lung cancer, glioma,
myeloproliferative neoplasms, and acute myeloid leukemia. Our results confirm
that the TERT rs2736100 polymorphism confers increased overall cancer risk.
PMID- 28418880
TI - Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance
in chronic myeloid leukemia cells.
AB - Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase
inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid
leukemia (CML). Imatinib resistance often results from a secondary mutation in
BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR
ABL1-independent resistance must be elucidated. To gain insight into the
mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array
based comparative genomic hybridization. We identified various resistance-related
genes, and focused on MET. Treatment with a MET inhibitor resensitized K562/IR
cells to BCR-ABL1 TKIs. Combined treatment of K562/IR cells with imatinib and a
MET inhibitor suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and c
Jun N-terminal kinase (JNK) activation, but did not affect AKT activation. Our
findings implicate the MET/ERK and MET/JNK pathways in conferring resistance to
imatinib, providing new insights into the mechanisms of BCR-ABL1 TKI resistance
in CML.
PMID- 28418881
TI - Aspirin as a potential modality for the chemoprevention of breast cancer: A dose
response meta-analysis of cohort studies from 857,831 participants.
AB - BACKGROUND: Previous meta-analyses on the relationship between aspirin use and
breast cancer risk have drawn inconsistent results. In addition, the threshold
effect of different doses, frequencies and durations of aspirin use in preventing
breast cancer have yet to be established. RESULTS: The search yielded 13
prospective cohort studies (N=857,831 participants) that reported an average of
7.6 cases/1,000 person-years of breast cancer during a follow-up period of from
4.4 to 14 years. With a random effects model, a borderline significant inverse
association was observed between overall aspirin use and breast cancer risk, with
a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model
was a better fit for the dose-response relationship, which displayed a potential
relationship between the frequency of aspirin use and breast cancer risk (RR =
0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It
was also a better fit for the duration of aspirin use and breast cancer risk (RR
= 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use). METHODS: We
searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for
relevant prospective cohort studies of aspirin use and breast cancer risk. Meta
analysis of relative risks (RR) estimates associated with aspirin intake were
presented by fixed or random effects models. The dose-response meta-analysis was
performed by linear trend regression and restricted cubic spline regression.
CONCLUSION: Our study confirmed a dose-response relationship between aspirin use
and breast cancer risk. For clinical prevention, long term (>5 years) consistent
use (2-7 times/week) of aspirin appears to be more effective in achieving a
protective effect against breast cancer.
PMID- 28418882
TI - Oncogenic histone methyltransferase EZH2: A novel prognostic marker with
therapeutic potential in endometrial cancer.
AB - The histone methyltransferase EZH2, a key epigenetic modifier, is known to be
associated with human tumorigenesis. However, the physiological importance of
EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in
the present study, we investigated the expression and function of EZH2 in
endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial
cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was
significantly overexpressed in cancer cells and tissues compared to that in
corresponding normal control cells and tissues. Kaplan-Meier survival analysis
using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated
that EZH2 overexpression is associated with endometrial cancer prognosis. In
addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression
and apoptosis induction of endometrial cancer cells, accompanied by attenuation
of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a
specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased
the number of cancer cell colonies. Furthermore, GSK126 showed additive effects
with doxorubicin or cisplatin, which are conventional drugs for treatment of
endometrial cancer. Further studies should explore the therapeutic potential of
inhibiting EZH2 in patients with endometrial cancer.
PMID- 28418883
TI - Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and
proliferation.
AB - Targeting cancer stem cells during initial treatment is important to reduce
incidence of recurrent disease. Bmi1 has been associated with cancer stem cell
self-renewal and aggressive disease. The purpose of this study was to determine
the effects of downregulation of Bmi1 in breast cancer stem cells in order to
target and eliminate the stem cell population in the tumor mass. Bmi1 was
downregulated using two approaches in the mouse breast cancer stem cell line FMMC
419II-a small molecule inhibitor (PTC 209) and stable transfection with a Bmi1
shRNA plasmid. The functional effect of Bmi1 downregulation was tested in vitro
and in vivo. Each approach led to decreased Bmi1 expression that correlated with
an inhibition of cancer stem cell properties in vitro including cell cycle arrest
and reduced mammosphere forming potential, and a decrease in tumor mass in vivo
after either intra-tumoral or systemic nanoparticle-targeted delivery of anti
Bmi1. These results show that inhibiting Bmi1 expression in breast cancer stem
cells could be important for the complete elimination of tumor and potentially
preventing disease relapse.
PMID- 28418884
TI - The association between miR-423 rs6505162 polymorphism and cancer susceptibility:
a systematic review and meta-analysis.
AB - The association between miR-423 polymorphism (C > A) and the risk of different
cancers are still controversial. We performed a meta-analysis to clarify its
association with multiple cancer risks. PubMed and Embase (as of 10th September,
2016) were searched. A total of 17 studies from 16 articles, consisting of 8,582
cases and 10,291 controls, were finally qualified and enrolled in this meta
analysis. The pooled results showed that the miR-423 AA genotype was associated
with decreased cancer risk under the recessive model (odds ratio [OR] = 0.87, 95%
confidence interval [CI]: 0.78~0.98, P = 0.020). However, this association became
non-significant after excluding the study with the smallest odds ratio. Subgroup
analyses revealed a significant decrease in risk of lung cancer (dominant model:
OR = 0.73, 95 % CI: 0.60~0.89, P = 0.002; recessive model: OR = 0.59, 95 % CI:
0.37~0.95, P = 0.031). Our study indicates that miR-423 rs6505162 might be
associated with a reduced risk of cancers, however, this finding need to be
evaluated further in larger samples, especially subgroup analyses. In addition,
cancer-specific functional studies are especially needed to reveal the underlying
mechanisms between miR-423 and the etiology of cancer.
PMID- 28418885
TI - Development of [11C]vemurafenib employing a carbon-11 carbonylative Stille
coupling and preliminary evaluation in mice bearing melanoma tumor xenografts.
AB - Over the last decade kinase inhibitors have witnessed tremendous growth as anti
cancer drugs. Unfortunately, despite their promising clinical successes, a large
portion of patients does not benefit from these targeted therapeutics.
Vemurafenib is a serine/threonine kinase inhibitor approved for the treatment of
melanomas specifically expressing the BRAFV600E mutation. The aim of this study
was to develop vemurafenib as PET tracer to determine its potential for
identification of tumors sensitive to vemurafenib treatment. Therefore,
vemurafenib was labeled with carbon-11 and analyzed for its tumor targeting
potential in melanoma xenografts Colo829 (BRAFV600E) and MeWo (BRAFwt) using
autoradiography on tissue sections, in vitro tumor cell uptake studies and
biodistribution studies in xenografted athymic nu/nu mice. [11C]vemurafenib was
synthesized in 21 +/- 4% yield (decay corrected, calculated from [11C]CO) in >
99% radiochemical purity and a specific activity of 55 +/- 18 GBq/MUmol. Similar
binding of [11C]vemurafenib was shown during autoradiography and cellular uptake
studies in both cell lines. Plasma metabolite analysis demonstrated > 95% intact
[11C]vemurafenib in vivo at 45 minutes after injection, indicating excellent
stability. Biodistribution studies confirmed the in vitro results, showing
similar tumor-to-background ratios in both xenografts models. These preliminary
results suggest that identification of BRAFV600E mutations in vivo using PET with
[11C]vemurafenib will be challenging.
PMID- 28418886
TI - Histone hypoacetylation contributes to CXCL12 downregulation in colon cancer:
impact on tumor growth and cell migration.
AB - CXCL12 has been shown to be involved in colon cancer metastasis, but its
expression level and molecular mechanisms regulating its expression remain
controversial. We thus evaluated CXCL12 expression in a large cohort of colon
adenomas and carcinomas, investigated for an epigenetic mechanism controlling its
expression and evaluated the impact of CXCL12 levels on cell migration and tumor
growth. CXCL12 expression was measured in human colon adenomas and carcinomas
with transcriptome array and RT-qPCR. The promoter methylation was analyzed with
whole-genome DNA methylation chips and protein expression by
immunohistochemistry. We confirm a reduced expression of CXCL12 in 75% of MSS
carcinomas and show that the decrease is an early event as already present in
adenomas. The methylome analysis shows that the CXCL12 promoter is methylated in
only 30% of microsatellite-stable tumors. In vitro, treatments with HDAC
inhibitors, butyrate and valproate restored CXCL12 expression in three colon cell
lines, increased acetylation of histone H3 within the CXCL12 promoter and
inhibited cell migration. In vivo, valproate diminished (65%) the number of
intestinal tumors in APC mutant mice, slowed down xenograft tumor growth
concomitant to restored CXCL12 expression. Finally we identified loss of PCAF
expression in tumor samples and showed that forced expression of PCAF in colon
cancer cell lines restored CXCL12 expression. Thus, reduced PCAF expression may
participate to CXCL12 promoter hypoacetylation and its subsequent loss of
expression. Our study is of potential clinical interest because agents that
promote or maintain histone acetylation through HDAC inhibition and/or HAT
stimulation, may help to lower colon adenoma/carcinoma incidence, especially in
high-risk families, or could be included in therapeutic protocols to treat
advanced colon cancer.
PMID- 28418887
TI - Metastasis-associated protein 3 in colorectal cancer determines tumor recurrence
and prognosis.
AB - Metastasis-associated protein family (MTA) promotes tumor cell invasion and
metastasis of human malignancies. However, the novel component of MTA family,
MTA3 was found to play conflicting roles in human malignancies. While the
expression pattern and potential function of MTA3 in colorectal cancer has not
been addressed yet. In the present study, we investigated the protein expression
of MTA3 by immunohistochemistry assay, analyzed its association with tumor
progression, recurrence and prognosis in239 cases of patients. Results showed
that MTA3 expression in colorectal cancer was significantly decreased in
colorectal cancer compared with normal specimens. Its expression was found to be
correlated with tumor differentiation, metastases and TNM stage. Kaplan-Meier
analysis proved that MTA3 was associated with both disease-free survival and
overall survival of patients with colorectal cancer that patients with negative
MTA3 expression tend to have unfavorable outcome. Moreover, cox's proportional
hazards analysis showed that negative MTA3 expression was an independent
prognostic marker of poor outcome. These results provided the first evidence that
MTA3 level was decreased in colorectal cancer and significantly correlated with
tumor cell invasion and metastasis. It also demonstrated that MTA3 might serve as
a potential marker of tumor recurrence and prognosis of colorectal cancer.
PMID- 28418888
TI - Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous
cell carcinoma and its potential as a target for anti-metastasis therapy.
AB - Metastasis is the most lethal hallmark of esophageal squamous cell carcinoma
(ESCC). The aim of the study is to identify key signaling pathways that control
metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were
established through three rounds of selection of cancer cells invading through
matrigel-coated chambers. Gene expression profile of one of the I3 sublines was
compared with that of its parental cell line using cDNA microarray analysis. Gene
ontology and pathway analyses of the differentially expressed genes (both
upregulated and downregulated) indicated that genes associated with cellular
movement and the AKT pathway were associated with increased cancer cell
invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p
AKT), N-cadherin and decreased E-cadherin expression in the I3 cells.
Immunohistochemistry was used to evaluate the clinical significance of p-AKT
expression in ESCC, and the results showed higher p-AKT nuclear expression in
lymph node metastases when compared with primary carcinoma. Inactivation of the
PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted
in reversed cadherin switching and inhibited cancer cell motility. Inhibition of
the pathway by treatment with wortmannin markedly suppressed experimental
metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT
signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic
target in treatment of metastatic ESCC.
PMID- 28418890
TI - The serum 25-hydroxyvitamin D levels and hip fracture risk: a meta-analysis of
prospective cohort studies.
AB - Hip fracture has increasingly become a social and economic burden. The
relationship between serum 25-hydroxyvitamin D levels and the risk of hip
fracture reported by previous studies remains controversial. We searched Pubmed
and Embase to identify studies reporting the relationship between serum 25
hydroxyvitamin D levels and risk of hip fracture. Fifteen prospective cohort
studies with a total of 51239 participants and 3386 hip fracture cases were
included. By pooling the Relative Risk of the lowest vs. the highest categories
indicated that lower levels of serum 25-hydroxyvitamin D were more likely to be a
risk factor for hip fracture with adjusted Relative Risk (95%Confidence Interval)
of 1.58 (1.41, 1.77). Subgroup meta-analysis examining the stability of the
primary results achieved the same results. A dose-response meta-analysis showed
that the risk of hip fracture was a descending curve below the line of RR=1. The
descending trend was obvious when serum 25-hydroxyvitamin D levels were less than
60 nmol/L and was flat when serum 25-hydroxyvitamin D levels were more than 60
nmol/L. We found that individuals with low levels of serum 25-hydroxyvitamin D
have an increased risk of hip fracture, and this effect was evident when the
serum 25-hydroxyvitamin D levels were less than 60 nmol/L.
PMID- 28418894
TI - Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell
renal cell carcinoma.
AB - Clear cell Renal Cell Carcinoma (ccRCC) causes over 13,000 deaths each year, and
about 20,000 new cases/year in Europe. In most cases, the causes are unknown and,
most importantly, there are no reliable biomarkers for the diagnosis and
prognosis of this disease. The search for sensitive biomarkers for early
diagnosis and prognosis of clear cell Renal Cell Carcinoma (ccRCC) is currently a
fast growing field. We carried out proteomics analysis of 93 urinary samples of
healthy subjects (HS) and patients affected by ccRCC, prostate cancer (PCa) and
chronic kidney disease (CKD), that was able to successfully distinguish each
group.The most significant candidate biomarker was identified by mass
spectrometry as Raf Kinase Inhibitor Protein (RKIP), a key regulator of cell
signaling, already described in several cancer types as a metastasis suppressor.
By combining ELISA, immunoblotting and tissue microarray, we demonstrated that,
in ccRCC, urinary excretion of RKIP and its phosphorylated form (p-RKIP)
reflected the tissue expression of these putative biomarkers. Baseline urinary
RKIP, evaluated in an independent cohort of 56 ccRCC patients and 28 HS,
successfully distinguished both groups and, most importantly, a cut-off value of
10 ng/mg/g Pr/uCr enabled a highly accurate prediction of Cancer-specific
survival and Progression-free survival. Furthermore, p-RKIP was totally
undetectable in both tissue and urine samples of ccRCC, showing a great potential
for diagnostics purposes.Our data indicate that urinary RKIP encompasses both the
unphosphorylated and the phosphorylated form and that their combined evaluation
can help in the diagnosis and prognosis of ccRCC.
PMID- 28418892
TI - Roles of long noncoding RNAs in colorectal cancer metastasis.
AB - Colorectal cancer (CRC) is the 3rd most common malignancies worldwide. Metastasis
is responsible for more than 90% CRC patients' death. Long noncoding RNAs
(lncRNAs) are an important class of transcribed RNA molecules greater than 200
nucleotides in length. With the development of whole genome sequencing
technologies, they have been gained more attention. Accumulating evidences
suggest that abnormal expression of lncRNAs in diverse diseases are involved in
various biological functions such as proliferation, apoptosis, metastasis and
differentiation by acting as epigenetic, splicing, transcriptional or post
transcriptional regulators. Aberrant expression of lncRNAs has also been found in
CRC. Besides, recent studies have indicated that lncRNAs play important roles in
tumourigenesis and cancer metastasis. They participate in the process of
metastasis by activing or inhibiting the metastatic pathways. However, their
functions on the development of cancer metastasis are poorly understood. In this
review, we highlight the findings of roles for lncRNAs in CRC metastasis and
review the metastatic pathways of lncRNAs leading to cancer metastasis in CRC,
including escape of apoptosis, epithelial-mesenchymal transition (EMT),
angiogenesis and invasion, migration and proliferation. Furthermore, we also
discuss the potential clinical application of lncRNAs in CRC as diagnostic
markers and therapeutic targets.
PMID- 28418896
TI - NFkB is essential for activin-induced colorectal cancer migration via
upregulation of PI3K-MDM2 pathway.
AB - Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic
disease. Activin and TGFB (TGFbeta) signaling are growth suppressive pathways
that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We
have recently shown that activin downregulates p21 via ubiquitination and
degradation associated with enhanced cellular migration independent of SMADs. To
investigate the mechanism of metastatic activin signaling, we examined activated
NFkB signaling and activin ligand expression in CRC patient samples and found a
strong correlation. We hypothesize that activation of the E3 ubiquitin ligase
MDM2 by NFkB leads to p21 degradation in response to activin treatment. To
dissect the link between activin and pro-carcinogenic NFkB signaling and
downstream targets, we found that activin but not TGFB induced activation of NFkB
leading to increased MDM2 ubiquitin ligase via PI3K. Further, overexpression of
wild type p65 NFkB increased MDM2 expression while the NFkB inhibitors NEMO
binding domain (NBD) and Bay11-7082 blocked the activin-induced increase in MDM2.
In conclusion, in colon cancer cell migration, activin utilizes NFkB to induce
MDM2 activity leading to the degradation of p21 in a PI3K dependent mechanism.
This provides new mechanistic knowledge linking activin and NFkB signaling in
advanced colon cancer which is applicable to targeted therapeutic interventions.
PMID- 28418897
TI - Treatment for retropharyngeal metastatic undifferentiated squamous cell carcinoma
from an unknown primary site: results of a prospective study with irradiation to
nasopharyngeal mucosa plus bilateral neck.
AB - : Background and Objetive: To evaluate treatment outcomes for patients with
retropharyngeal metastatic undifferentiated squamous cell carcinoma (SCC) from an
unknown primary site. METHODS: From January 2005 to January 2015, patients who
presented with enlarged retropharyngeal nodes underwent transoral sonography
guided fine-needle aspiration to confirm histology. Those with metastatic
undifferentiated SCC with unknown primary tumors were treated with radical
radiotherapy to nasopharyngeal mucosa plus bilateral neck. Chemotherapy was
administered for patients staged N2-3. Endpoints included metastatic nodes
control, the appearance of primary tumor, overall survival and treatment-related
toxicities. RESULTS: A total of 49 patients were recruited into this study.
Retropharyngeal and cervical nodal disease was controlled in 96% of all patients.
The incidence of occult primary cancer appearance was 8%. No primary cancer other
than of the nasopharynx was detected during the course of follow-up. Ten patients
developed distant metastases. The 5-year overall survival, progression-free
survival, regional relapse free survival, distant metastasis free survival were
79.6%, 61.1%, 83.4%, 73.8%, respectively. Common late adverse effects included
xerostomia (57%) and hearing impairment (35%). CONCLUSION: Radical radiotherapy
to both the nasopharynx and bilateral neck can achieve excellent outcome with
mild toxicities for patients with retropharyngeal metastatic undifferentiated
squamous cell carcinoma from an unknown primary site.
PMID- 28418898
TI - PLCE1 polymorphisms and expression combined with serum AFP level predicts
survival of HBV-related hepatocellular carcinoma patients after hepatectomy.
AB - Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in
the development and progression of several types of cancer. The present study
investigated the prognostic significance of PLCE1 gene polymorphisms and
expression combined with serum alpha-fetoprotein (AFP) level in hepatitis B virus
(HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms
were genotyped by sequencing DNA isolated from surgically resected tumor samples
of 421 HBV-related HCC patients, and expression profiles were generated based on
the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes
(Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20
ng/ml showed a significant association with overall survival(OS) of HBV-related
HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP
level >= 20 ng/ml had an increased risk of death as compared to those with the AC
haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively).
Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased
risk of death, although with a non-significant P value (adjusted P=0.092). Joint
effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300
ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our
results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and
expression combined with serum AFP level may predict postoperative outcome of HBV
related HCC patients.
PMID- 28418899
TI - An exploration of the role of a fish-oriented diet in cognitive decline: a
systematic review of the literature.
AB - Epidemiological studies have presented inconsistent evidence of the correlation
between a fish-oriented dietary intake (FDI) and the risk of cognitive decline.
To address these controversies, we performed this systematic review of
prospective studies published in December 2016 and earlier using PubMed, Embase,
and Web of Science. Two independent researchers conducted the eligibility
assessment and data extraction; all discrepancies were solved by discussion with
a third researcher. The pooled relative risks (RRs) focused on the incidence of
events were estimated with 95% confidence intervals (CIs). Overall, nine studies
containing 28,754 subjects were analyzed. When the highest and lowest categories
of fish consumption were compared, the summary RR for dementia of Alzheimer type
(DAT) was 0.80 (95%CI = 0.65-0.97); i.e., people with a higher intake of fish had
a 20% (95%CI = 3-35%) decreased risk of DAT. Additionally, the dose-response
synthesized data indicated that a 100-g/week increase in fish intake reduced the
risk of DAT by an additional 12% (RR = 0.88, 95%CI = 0.79-0.99). Non-significant
results were observed for the risk of dementia of all causes (DAC) and mild
cognitive impairment (MCI). Limited evidence involving heterogeneity was found
within subgroups or across studies. In conclusion, this review confirmed that a
higher intake of fish could be correlated with a reduced risk of DAT. Further
research, especially prospective studies that specifically quantify FDI, will
help find a more accurate assessment of the different levels of dietary intake.
PMID- 28418900
TI - Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: a
strategy to overcome TP53 mutated/deleted clones.
AB - Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder with either
indolent or aggressive clinical course. Current treatment regiments have
significantly improved the overall outcomes even if higher risk subgroups - those
harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p)
remain highly challenging. In the present work, we identified USP7, a known de
ubiquitinase with multiple roles in cellular homeostasis, as a potential
therapeutic target in CLL. We demonstrated that in primary CLL samples and in CLL
cell lines USP7 is: i) over-expressed through a mechanism involving miR-338-3p
and miR-181b deregulation; ii) functionally activated by Casein Kinase 2 (CK2),
an upstream interactor known to be deregulated in CLL; iii) effectively targeted
by the USP7 inhibitor P5091. Treatment of primary CLL samples and cell lines with
P5091 induces cell growth arrest and apoptosis, through the restoration of PTEN
nuclear pool, both in TP53-wild type and -null environment. Importantly, PTEN
acts as the main tumor suppressive mediator along the USP7-PTEN axis in a p53
dispensable manner. In conclusion, we propose USP7 as a new druggable target in
CLL.
PMID- 28418901
TI - Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal
carcinoma patients: a network meta-analysis.
AB - OBJECT: A Bayesian network meta-analysis (NMA) was conducted to estimate the
overall survival (OS) and complete response (CR) performance in nasopharyngeal
carcinoma (NPC) patients who have been given the treatment of radiotherapy,
concurrent chemoradiotherapy (C), adjuvant chemotherapy (A), neoadjuvant
chemotherapy (N), concurrent chemoradiotherapy with adjuvant chemotherapy (C+A),
concurrent chemoradiotherapy with neoadjuvant chemotherapy (C+N) and neoadjuvant
chemotherapy with adjuvant chemotherapy (N+A). METHODS: Literature search was
conducted in electronic databases. Hazard ratios (HRs) accompanied their 95%
confidence intervals (95%CIs) or 95% credible intervals (95%CrIs) were applied to
measure the relative survival benefit between two comparators. Meanwhile odd
ratios (ORs) with their 95% CIs or CrIs were given to present CR data from
individual studies. RESULTS: Totally 52 qualified studies with 10,081 patients
were included in this NMA. In conventional meta-analysis (MA), patients with N+C
exhibited an average increase of 9% in the 3-year OS in relation to those with
C+A. As for the NMA results, five therapies were associated with a significantly
reduced HR when compared with the control group when concerning 5-year OS. C, C+A
and N+A also presented a decreased HR compared with A. There was continuity among
1-year, 3-year and 5-year OS status. Cluster analysis suggested that the three
chemoradiotherapy appeared to be divided into the most compete group which is
located in the upper right corner of the cluster plot. CONCLUSION: In view of
survival rate and complete response, the NMA results revealed that C, C+A and C+N
showed excellent efficacy. As a result, these 3 therapies were supposed to be
considered as the first-line treatment according to this NMA.
PMID- 28418902
TI - IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance
to erlotinib in HCC827 NSCLC cells.
AB - EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2
years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance
mechanisms have been identified including secondary EGFR-mutations, MET
amplification, and epithelial-mesenchymal transition (EMT). Previous studies have
indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired
resistance to EGFR-directed drugs as well as in EMT. In the present study, we
have investigated the involvement of IGF1R in acquired high-dose erlotinib
resistance in the EGFR-mutated lung adenocarcinoma cell line HCC827. We observed
that IGF1R was upregulated in the immediate response to erlotinib and
hyperactivated in erlotinib resistant HCC827 cells. Resistant cells additionally
acquired features of EMT, whereas MET-amplification and secondary EGFR-mutations
were absent. Using CRISPR/Cas9, we generated a HCC827(IGFR1-/-) cell line and
subsequently investigated resistance development in response to high-dose
erlotinib. Interestingly, HCC827(IGFR1-/-) cells were now observed to
specifically amplify the MET gene. Additionally, we observed a reduced level of
mesenchymal markers in HCC827(IGFR1-/-) indicating an intrinsic enhanced
epithelial signature compared to HCC827 cells. In conclusion, our data show that
IGF1R have an important role in defining selected resistance mechanisms in
response to high doses of erlotinib.
PMID- 28418903
TI - Kinomic profiling identifies focal adhesion kinase 1 as a therapeutic target in
advanced clear cell renal cell carcinoma.
AB - The introduction of targeted therapies has caused a paradigm shift in the
treatment of metastatic clear cell (cc)-renal cell carcinoma (RCC). We
hypothesized that determining differential kinase activity between primary and
metastatic tumor sites may identify critical drivers of progression and relevant
therapeutic targets in metastatic disease. Kinomic profiling was performed on
primary tumor and metastatic tumor deposits utilizing a peptide substrate
microarray to detect relative tyrosine phosphorylation activity. Pharmacologic
and genetic loss of function experiments were used to assess the biologic
significance of the top scoring kinase on in vitro and in vivo tumor phenotypes.
Kinomics identified 7 peptides with increased tyrosine phosphorylation in
metastases that were significantly altered (p<0.005). Based on these peptides,
bioinformatics analyses identified several candidate kinases activated in
metastases compared to primary tumors. The highest ranked upstream kinase was
Focal Adhesion Kinase 1 (FAK1). RCC lines demonstrate evidence of elevated FAK1
activation relative to non-transformed renal epithelial cells. Pharmacologic
inhibition of FAK1 with GSK2256098 suppresses in vitro tumor phenotypes. In turn,
FAK1 knockdown in RCC cells suppresses both in vitro phenotypes and in vivo tumor
growth. Collectively, these data demonstrate functional activation of FAK1 in
metastases and provide preclinical rationale for targeting this kinase in the
setting of advanced ccRCC.
PMID- 28418904
TI - A consensus-hemagglutinin-based vaccine delivered by an attenuated Salmonella
mutant protects chickens against heterologous H7N1 influenza virus.
AB - H7N3 and H7N7 are highly pathogenic avian influenza (HPAI) viruses and have posed
a great threat not only for the poultry industry but for the human health as
well. H7N9, a low pathogenic avian influenza (LPAI) virus, is also highly
pathogenic to humans, and there is a great concern that these H7 subtypes would
acquire the ability to spread efficiently between humans, thereby becoming a
pandemic threat. A vaccine candidate covering all the three subtypes must,
therefore, be an integral part of any pandemic preparedness plan. To address this
need, we constructed a consensus hemagglutinin (HA) sequence of H7N3, H7N7, and
H7N9 based on the data available in the NCBI in early 2012-2015. This artificial
sequence was then optimized for protein expression before being transformed into
an attenuated auxotrophic mutant of Salmonella Typhimurium, JOL1863 strain.
Immunizing chickens with JOL1863, delivered intramuscularly, nasally or orally,
elicited efficient humoral and cell mediated immune responses, independently of
the route of vaccination. Our results also showed that JOL1863 deliver efficient
maturation signals to chicken monocyte derived dendritic cells (MoDCs) which were
characterized by upregulation of costimulatory molecules and higher cytokine
induction. Moreover, immunization with JOL1863 in chickens conferred a
significant protection against the heterologous LPAI H7N1 virus challenge as
indicated by reduced viral sheddings in the cloacal swabs. We conclude that this
vaccine, based on a consensus HA, could induce broader spectrum of protection
against divergent H7 influenza viruses and thus warrants further study.
PMID- 28418905
TI - Expression pattern of genome-scale long noncoding RNA following acute myocardial
infarction in Chinese Uyghur patients.
AB - In this study, we examined the long noncoding RNA (lncRNA) expression pattern in
Uyghur patients (a minority of China) with acute myocardial infarction (AMI) on a
genome-wide scale. Total RNAs were extracted from the peripheral blood of 55
Uyghur AMI patients and 55 healthy volunteers. The expression levels of genome
wide scale lncRNAs and mRNAs were determined by microarray in 10 samples (5 AMI
and 5 controls). qRT-PCR was used to validate lncRNA expression levels in 100
samples (50 AMI and 50 controls). Data analyses were performed using R and
Bioconductor. A total of 3624 up- and 1637 down-regulated lncRNAs were identified
to be significantly and differentially expressed between these two groups. The
annotation result of their co-expressed mRNAs showed that the most significantly
related category of GO analysis was regulation of biological processes, and the
most significantly related pathway was apoptosis and its corresponding p53. The
microarray identified ENST00000416860.2, ENST00000421157.1 and TCONS_00025701
lncRNAs were confirmed by qRT-PCR. Our study indicated that clusters of lncRNAs
were significantly and differentially expressed in the peripheral blood of AMI
patients when compared with healthy controls within the Uyghur population. These
newly identified lncRNAs may have a potential role in the development of AMI.
PMID- 28418906
TI - The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical
outcomes of breast cancer patients in northern China.
AB - BACKGROUND: Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the
differentiation of clinical outcomes among breast cancer women. This study aimed
to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4
genes with clinicopathological features, protein expression and prognosis of
breast cancer in the northern Chinese population. RESULTS: Firstly, SNP
rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated
with age and menstruation status. And SNP rs11636419 and rs17861162 were
associated with the P53 status. Secondly, SNP rs2470890 was correlated with
CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P
= 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan-Meier 5 year
survival curves showed that patients carrying genotypes CT or TT had a worse OS
compared with the genotype CC carriers under both codominant and dominant model
(P < 0.001, P < 0.001, respectively). MATERIALS AND METHODS: Four single
nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer
patients using the SNaPshot method. The associations of four polymorphisms with
protein expression and clinicopathological characteristics were evaluated by
Pearson's chi-square test. The Cox hazard regression analysis and Kaplan-Meier
survival analysis were performed to evaluate the relationship between the SNPs
and overall survival (OS) of breast cancer. CONCLUSIONS: CYP1A2 rs2470890 was
significantly associated with the prognosis of patients with breast cancer and
could serve as an independent impact factor of prognosis of breast carcinoma.
PMID- 28418907
TI - BH3-mimetics and BET-inhibitors elicit enhanced lethality in malignant glioma.
AB - Drug combination therapies remain pivotal for the treatment of heterogeneous
malignancies, such as glioblastomas. Here, we show a novel lethal interaction
between Bcl-xL and c-myc inhibition accomplished by bromodomain protein
inhibitors. Established, patient-derived xenograft and stem cell-like glioma
cells were treated with the novel bromodomain protein inhibitors, JQ1 and OTX015,
along with BH3-mimetics, ABT263 or Obatoclax. Synergy was assessed by calculation
of CI values. Small interfering RNAs (siRNAs) were used for gene silencing and
mechanistic studies. In vivo experiments were performed in a glioblastoma
xenograft model. Single treatments with JQ1 and OTX015 had only moderate effects
on the reduction of cellular viability. However, the combination treatment of BH3
mimetics along with JQ1 or OTX015 resulted in a highly synergistic reduction of
cellular viability in a broad range of different model systems of malignant
glioma. Similarly, knockdown of c-myc sensitized glioma cells for ABT263 mediated
cell death. The enhanced loss of cellular viability in the combination treatment
was mediated by activation of apoptosis with dissipation of mitochondrial
membrane potential and caspase cleavage. The combination treatment led to a
modulation of anti- and pro-apoptotic Bcl-2 family members with an increase in
pro-apoptotic Noxa mediated by ATF4. Small interfering RNA mediated knockdown of
Bak and Noxa protected glioma cells from ABT263/JQ1 mediated apoptosis. Finally,
the combination treatment of ABT263 and OTX015 resulted in a regression of tumors
and a significantly smaller tumor size as compared to single or vehicle treated
tumors. Thus, these results warrant clinical testing for the drug combination of
BH3-mimetics along with bromodain protein inhibitors.
PMID- 28418909
TI - Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and
mechanisms underlying its relapse.
AB - ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic
leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the
molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed
by a series of secondary mutations that trigger overt leukemia. The cellular
framework in which E/R arises and the maintenance of a pre-leukemic condition by
E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly,
a variety of studies have focused on the relationship between the clones giving
rise to the primary and recurrent E/R-positive ALL. We review here the most
recent insights into the pathogenic mechanisms underlying E/R-positive ALL, as
well as the molecular abnormalities prevailing at relapse.
PMID- 28418911
TI - Elevated serum level of pancreatic stone protein/regenerating protein (PSP/reg)
is observed in diabetic kidney disease.
AB - : Diabetic kidney disease (DKD) is a major complication of diabetes, and serves
as an important cause of end-stage renal disease (ESRD). The role of chronic
inflammation in DKD is becoming widely accepted. Pancreatic stone
protein/regenerating protein (PSP/reg) is a secretory protein, which is elevated
in blood during infected conditions and organ failure. The aim of this study was
to investigate the relationship between serum PSP/reg and DKD in patients with
type 2 diabetes (T2DM). A total of 120 subjects which includes newly diagnosed
T2DM patients, diabetes patients without DKD, DKD patients, as well as healthy
controls were enrolled in this study. Serum PSP/reg levels were significantly
higher in DKD subjects compared with those of healthy controls (p < 0.001), newly
diagnosed T2DM (p < 0.001) and diabetes patients without DKD (p < 0.001). PSP/reg
levels correlated positively with glycated hemoglobin (HbA1c) (p < 0.001) and
serum creatinine (p < 0.001). Meanwhile, serum PSP level was negatively
correlated with estimated glomerular filtration rate (eGFR) (p < 0.001). The area
under the curve (AUC) for presence of DKD was 0.854. IN CONCLUSION: PSP/reg
levels are significantly up-regulated in DKD patients and might be related to
renal injury. A follow-up study with a large cohort is needed.
PMID- 28418910
TI - Erythropoietin drives breast cancer progression by activation of its receptor
EPOR.
AB - Breast cancer is a leading cause of cancer-related deaths. Anemia is common in
breast cancer patients and can be treated with blood transfusions or with
recombinant erythropoietin (EPO) to stimulate red blood cell production. Clinical
studies have indicated decreased survival in some groups of cancer patients
treated with EPO. Numerous tumor cells express the EPO receptor (EPOR), posing a
risk that EPO treatment would enhance tumor growth, but the mechanisms involved
in breast tumor progression are poorly understood.Here, we have examined the
functional role of the EPO-EPOR axis in pre-clinical models of breast cancer. EPO
induced the activation of PI3K/AKT and MAPK pathways in human breast cancer cell
lines. EPOR knockdown abrogated human tumor cell growth, induced apoptosis
through Bim, reduced invasiveness, and caused downregulation of MYC expression.
EPO-induced MYC expression is mediated through the PI3K/AKT and MAPK pathways,
and overexpression of MYC partially rescued loss of cell proliferation caused by
EPOR downregulation. In a xenotransplantation model, designed to simulate
recombinant EPO therapy in breast cancer patients, knockdown of EPOR markedly
reduced tumor growth.Thus, our experiments in vitro and in vivo demonstrate that
functional EPOR signaling is essential for the tumor-promoting effects of EPO and
underline the importance of the EPO-EPOR axis in breast tumor progression.
PMID- 28418912
TI - Human microRNA expression in sporadic and FAP-associated desmoid tumors and
correlation with beta-catenin mutations.
AB - Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging
histological diagnosis. DTs can occur sporadically or associated with the
familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with
beta-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease.
microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile
was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens
of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred
and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP
associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then
validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with
healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational
status in sporadic DTs. The correlation between sporadic DTs and miRNA expression
showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p
was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3,
as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was
also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect
the genesis and the progression of this disease and help histological diagnosis
of sporadic DTs.
PMID- 28418913
TI - Accumulation of myeloid-derived suppressor cells (MDSCs) induced by low levels of
IL-6 correlates with poor prognosis in bladder cancer.
AB - Bladder cancer (BC) is one of the most commonly occurring cancers, with a high
recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here,
we analyzed the markers and significance of myeloid-derived suppressor cells
(MDSCs) for BC development and progression. MDSC markers were examined in
peripheral blood from 113 BC patients and 20 healthy volunteers. We identified
CD11b+CD33lowHLA-DR- CD3- cells as markers of MDSCs in peripheral blood from BC
patients. We also demonstrated that MDSC numbers are higher in BC patients than
healthy donors, and that MDSC numbers correlate with the clinical grade, stage,
and poor prognosis. In addition, serum IL-6 levels are decreased in BC patients
with higher MDSC counts. IL-6 blockade increases induction of MDSCs in vitro. Low
IL-6 levels inhibit activation of Stat3, resulting in the increased formation of
MDSCs in BC. These results indicate that the MDSCs numbers may serve as a novel
prognostic marker in BC patients, and that targeting IL-6 signaling may be a
promising strategy for BC treatment.
PMID- 28418914
TI - MET exon 14 mutations as targets in routine molecular analysis of primary
sarcomatoid carcinoma of the lung.
AB - MET exon 14 splicing mutations are new targetable oncogenic drivers reported in
3% of non-small cell lung cancer (NSCLC) cases and have been shown to be more
common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen
mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian
patients, with a large adenocarcinoma cohort as internal control.We tested 81
patients with SC and 150 with adenocarcinoma for splice site DNA mutations
leading to RNA splicing-based skipping of MET exon 14. To this end, we employed a
mass spectrometry-based custom-designed PCR assay for routine analysis of whole
MET exon 14 and flanking intronic regions using formalin-fixed paraffin-embedded
(FFPE) tumor samples.Our results revealed a 4.9% mutation rate for MET exon 14
mutations in Caucasian SC patients, which is, though highly variable, within the
usual range reported in NSCLC. Discrepancies with previous results reported in SC
could be accounted for the small number of cases, ethnicity, epithelial
component, and percentage of other driver mutations, such as KRAS, in the patient
populations studied. Based on our study findings, SC patients should be screened
for MET exon 14 mutations in the same manner as adenocarcinoma patients.
PMID- 28418916
TI - Clinicopathologic study of invasive micropapillary carcinoma of the breast.
AB - Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma.
It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though
it is uncertain whether the prognoses of IMPC and IDC differ. In this
retrospective study, we compared the clinicopathologic characteristics and
survival between 170 female patients with IMPC (pure or mixed with IDC) and 728
with pure IDC. The IMPC patients had higher clinical stages and histologic
grades, higher incidences of lymphovascular invasion and axillary lymph node
extracapsular extension, and a higher degree of lymph node involvement than IDC
patients. Moreover, IMPC was associated with increases in estrogen receptor (ER)
and progesterone receptor (PR) positivity and HER-2 overexpression. Although
locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS)
were poorer in IMPC patients than IDC patients, overall survival and distant
metastasis survival did not differ between the two groups. Multivariate analysis
revealed that IMPC was an independent prognostic factor for LRRFS in breast
cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer
RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment
decisions, patients with breast carcinoma be tested for the presence of this
specific subtype.
PMID- 28418915
TI - MTA1 promotes epithelial to mesenchymal transition and metastasis in non-small
cell lung cancer.
AB - The present study assessed the role of metastasis-associated protein 1 (MTA1) in
epithelial to mesenchymal transition (EMT) and metastasis in non-small-cell lung
cancer (NSCLC) cells using a normal lung epithelium cell line, three NSCLC cell
lines, a mouse NSCLC model, and 56 clinical NSCLC samples. We observed that MTA1
overexpression decreased cellular adhesion, promoted migration and invasion, and
changed cytoskeletal polarity. MTA1 knockdown had the opposite effects. MTA1
overexpression decreased E-cadherin, Claudin-1, and ZO-1 levels and increased
Vimentin expression in vitro and in vivo, through activation of AKT/GSK3beta/beta
catenin signaling. However, treatment with the AKT inhibitor MK2206 did not
completely rescue effects associated with MTA1 expression changes, indicating
that pathways other than the AKT/GSK3beta/beta-catenin pathway could be involved
in MTA1-induced EMT. Compared with normal lung tissues, MTA1 expression was
elevated in NSCLC patient tissues and was correlated with American Joint
Committee on Cancer stage, T stage, lymphatic metastasis, and patient overall
survival. Additionally, MTA1 expression was positively associated with p-AKT and
cytoplasmic beta-catenin levels. These findings indicate MTA1 promotes NSCLC cell
EMT and metastasis via AKT/GSK3beta/beta-catenin signaling, which suggests MTA1
may be an effective anti-NSCLC therapeutic target.
PMID- 28418917
TI - Expression of guanylyl cyclase C in tissue samples and the circulation of rectal
cancer patients.
AB - Guanylyl cyclase C (GCC) is a transmembrane surface receptor restricted to
intestinal epithelial cells, from the duodenum to the rectum. We compared GCC
expression in tumors and normal rectal tissues, and investigated the relation
between GCC expression and metastasis and long-term survival of rectal cancer
patients. Based on the UICC classification, 42 rectal cancer patients in this
study were classified as stage I, 48 patients as stage II, and 90 patients as
stage III. Overexpression of GCC was observed in 80 rectal tumors as compared to
matched normal tissues, where no strong staining of GCC was observed. An
association between GCC mRNA in the circulation and tumor emboli in vessels, CK20
mRNA, distant organ metastasis, and survival status was observed in 100 rectal
cancer patients. Univariate Cox regression analysis indicated that tumor emboli
in vessels, lymph node metastasis, mesenteric root lymph node metastasis and GCC
mRNA correlated with 5-year disease-free survival (DFS); while lymph node
metastasis, GCC mRNA, and CK20 mRNA strongly correlated with 5-year overall
survival (OS). In a multivariate Cox regression model, GCC mRNA level and
mesenteric root lymph node metastasis associated with DFS, while GCC mRNA levels
associated with OS. Quantification of GCC expression in circulation is a valuable
biomarker for assessing tumor burden and predicting outcome in rectal cancer
patients.
PMID- 28418918
TI - The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in
advanced gastric signet-ring cell carcinoma, representing a potential biomarker
for immunotherapy.
AB - Recent data supports a potentially significant role for immune checkpoint
inhibitors in the treatment of gastric cancer. However, there are few data on the
clinical implications of immunotherapy markers in gastric signet-ring cell
carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1
(PD-1), programmed cell death ligand 1(PD-L1), infiltration by CD3+ T cell,
microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the
relationship of each factor to survival in 89 advanced SRCC patients. All
patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were
expressed in 40.4% and 18.0% of the patients, respectively. There was a
significant correlation between PD-L1 and PD-1 expression (r=0.363, p<0.001).
There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins
in 32.6% of samples. Only 1 case out of 89 was EBV positive, with concurrent PD
L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+
T cells numbers was associated with increased PD-1 expression (r=0.256, p=0.012)
and MSI status (r=0.208, p=0.049). High CD3+ T cell infiltration was related to
better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0,
p=0.033), but was not an independent prognostic factor for survival after
multivariate analysis (HR=0.68, 95% CI: 0.42-1.10, p=0.116). CD3+ T cell was more
infiltrated in PD-1 positive, tumors with MSI and were associated with better OS,
indicating an adaptive immune resistance may be occurring. Further research into
the cancer immunotherapy markers of SRCC immune microenvironment may highlight
targets for immunotherapy.
PMID- 28418919
TI - ZNF452 facilitates tumor proliferation and invasion via activating AKT-GSK3beta
signaling pathway and predicts poor prognosis of non-small cell lung cancer
patients.
AB - ZNF452 is a zinc-finger protein family member which contains an isolated SCAN
(SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) zinc-finger domain. Despite the SCAN
N-terminus domain is known to play a role in transcriptional regulation of genes
involved in cell survival and differentiation, there are no precise cellular
functions that have been assigned to ZNF452. In the present study, we found that
either endogenous or exogenous ZNF452 was overexpressed in the cytoplasm of NSCLC
cells and positive ratio of ZNF452 in NSCLC samples (50.8%, 93/183) was
significantly higher than that in normal lung tissues (22.4%, 13/58, P<0.001).
ZNF452 overexpression was correlated with advanced TNM stage (P=0.033), positive
lymph node metastasis (P=0.002) and predicted poor overall survival of NSCLC
patients (P<0.001). ZNF452 facilitated tumor growth, colony formation, G1-S phase
arrest, migration and invasion through upregulating the levels of CyclinD1,
CyclinE1, p-Rb, or Snail, and downregulating the expression of Zo-1. In nude mice
xenografts, overexpressing ZNF452 also promoted tumor proliferation and
metastasis. Subsequently, we found that the effect of ZNF452 on facilitating
tumor proliferation and invasion was through activating its downstream AKT
GSK3beta signaling pathway. Treatment of AKT inhibitor markedly prevented the
phosphorylation of AKT and GSK3beta which subsequently counteracted increasing
expression of CyclinD1, CyclinE1 or Snail and restored the decreasing expression
of Zo-1, as well as the upregulation of tumor proliferation and invasion, caused
by ZNF452 overexpression.Taken together, the present study indicated that ZNF452
may be an upstream regulator of AKT-GSK3beta signaling pathway and facilitates
proliferation and invasion of NSCLC.
PMID- 28418920
TI - Complementary utility of targeted next-generation sequencing and
immunohistochemistry panels as a screening platform to select targeted therapy
for advanced gastric cancer.
AB - We tested the clinical utility of combined profiling of Ion Torrent PGM based
next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to
molecularly targeted therapies. A consecutive cohort of 93 patients with
advanced/metastatic GC who underwent palliative chemotherapy between March and
December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor
biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding
RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2,
MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53
protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay).
Treatment was based on availability of targeted agents at the time of molecular
diagnosis. Among the 81 cases with available tumor samples, complete NGS and IHC
profiles were successfully achieved in 66 cases (81.5%); only IHC results were
available for 15 cases. Eight cases received matched therapy based on sequencing
results; ERBB2 amplification, trastuzumab (n = 4); PIK3CA mutation, Akt inhibitor
(n = 2); and FGFR2 amplification, FGFR2b inhibitor (n = 2). Eleven cases received
matched therapy based on IHC; ERBB2 positivity, trastuzumab (n = 5); PTEN loss (n
= 2), PI3Kbeta inhibitor; MMR deficiency (n = 2), PD-1 inhibitor; and EGFR
positivity (n = 2), pan-ERBB inhibitor. A total of 19 (23.5%) and 62 (76.5%)
cases were treated with matched and non-matched therapy, respectively. Matched
therapy had significantly higher overall response rate than non-matched therapy
(55.6% vs 13.1%, P = 0.001). NGS and IHC markers provide complementary utility in
identifying patients who may benefit from targeted therapies.
PMID- 28418922
TI - Novel impact of the DNMT3A R882H mutation on GSH metabolism in a K562 cell model
established by TALENs.
AB - DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid
leukemia (AML) patients, and were considered to be an adverse prognostic factor
for adult de novo AML cases. However, the relevant molecular mechanism of the
mutation in AML pathogenesis remains obscure. In this study, we established K562
and SKM1 cell model carrying the DNMT3A R882H mutation via transcription
activator-like effector nuclease (TALEN) and Clustered regularly interspaced
short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated
DNMT3A could promote the proliferative capability of malignant cell clones.
Further RNA microarray analysis revealed that some genes crucial for glutathione
(GSH) synthesis, including CTH, PSPH, PSAT1 and especially SLC7A11 (the
cysteine/glutamate transporter) were significantly up-regulated, which resulted
in significant elevation of intracellular GSH levels. A subsequent experiment
demonstrated that the mutant clones are resistant to chemotherapy as well as
SLC7A11-inhibitorsBy shRNA induced SLC7A11 silencing, we discovered profoundly
decreased cellular GSH and cell proliferative ability of DNMT3A mutated clones.
Our results provided novel insight into the role of the DNMT3A R882H mutation in
AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway
could enhance the current therapy for AML patients with the DNMT3A R882H
mutation.
PMID- 28418923
TI - OSU-A9 inhibits pancreatic cancer cell lines by modulating p38-JAK-STAT3
signaling.
AB - Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of
death worldwide. Since there is a dire need for novel and effective therapies to
improve the poor survival rates of advanced pancreatic cancer patients, we
analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on
pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger
antitumor effect than gemcitabine on two pancreatic cancer cell lines, including
gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down
regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and
decreased phosphorylation of JAK and STAT3. Cell migration and invasiveness
assays showed that OSU-A9 reduced cancer cell aggressiveness and inhibited BxPC-3
xenograft growth in nude mice. These results suggest that OSU-A9 modulates the
p38-JAK-STAT3 signaling module, thereby inducing cytotoxicity in pancreatic
cancer cells. Continued evaluation of OSU-A9 as a potential therapeutic agent for
pancreatic cancer thus appears warrented.
PMID- 28418924
TI - RNA sequencing analyses reveal novel differentially expressed genes and pathways
in pancreatic cancer.
AB - Gene expression microarrays have identified many tumor markers and therapeutic
targets for pancreatic ductal adenocarcinoma (PDAC). However, microarray
profilings have limited sensitivity and are prone to cross-hybridization between
homologous DNA fragments. Here, we perform a transcriptome analysis of paired
tumor and adjacent benign pancreatic tissues from 10 patients who underwent
resection for PDAC. We identify a total of 2736 differentially expressed genes
(DEGs) with false discovery rate less than 0.05, including 1554 upregulated, 1182
downregulated, and 6 microRNAs (miR-614, miR-217, miR-27b, miR-4451, miR-3609,
and miR-612). Overexpression of five DEGs, i.e. KRT16, HOXA10, CDX1, SI, and
SERPINB5 in tumors is confirmed by RT-PCR in 20 additional tissues.
Overexpression of KRT16 in PDAC is also verified on protein level. In addition,
top canonical pathways such as granulocyte adhesion and diapedesis pathway have
been identified. Our study represents a comprehensive characterization of the
PDAC transcriptome and provides insight to the mechanisms of pancreatic
carcinogenesis and potential biomarkers and novel therapeutic targets for
pancreatic cancer.
PMID- 28418925
TI - Syntenin promotes VEGF-induced VEGFR2 endocytosis and angiogenesis by increasing
ephrin-B2 function in endothelial cells.
AB - Syntenin, a tandem PDZ-domain-containing scaffold protein, is involved in the
regulation of diverse biological functions, including protein trafficking,
exosome biogenesis, and cancer metastasis. Here, we present the first study to
explore the significance of syntenin in endothelial cells. Syntenin knockdown in
human umbilical vein endothelial cells (HUVECs) impaired vascular endothelial
growth factor (VEGF)-mediated proliferation, migration, invasion, vascular
permeability, and nitric oxide (NO) production. Syntenin knockdown also
suppressed expression of the VEGFR2 target genes VEGF, MMP2, and Nurr77 as well
as VEGF-induced angiogenesis in vitro and in vivo. And it decreased cell-surface
levels of ephrin-B2. Biochemical analyses revealed that syntenin exists in
complex with VEGFR2 and ephrin-B2. Syntenin knockdown abolished the association
between VEGFR2 and ephrin-B2, suggesting syntenin functions as a scaffold protein
facilitating their association in HUVECs. Consistent with these observations,
knocking down syntenin or ephrin-B2 abolished VEGF-induced endocytosis and VEGFR2
phosphorylation and activation of its downstream signaling molecules. Treatment
with MG132, a proteasome inhibitor, rescued the downregulation of ephrin-B2 and
VEGFR2 signaling induced by syntenin knockdown. These findings demonstrate that
syntenin promotes VEGF signaling and, through its PDZ-dependent interaction with
ephrin-B2, enhances VEGF-mediated VEGFR2 endocytosis and subsequent downstream
signaling and angiogenesis in endothelial cells.
PMID- 28418926
TI - Urinary kallikrein 10 predicts the incurability of gastric cancer.
AB - The current imaging modalities are not sufficient to identify inoperable tumor
factors, including distant metastasis and local invasion. Hence, we conducted
this study using urine samples to discover non-invasive biomarkers for the
incurability of gastric cancer (GC). Urine samples from 111 GC patients were
analyzed in this study. The GC cohort was categorized and analyzed according to
disease stage and operability. In the discovery phase, protease protein array
analysis identified 3 potential candidate proteins that were elevated in the
urine of advanced GC patients compared to early GC patients. Among them, urinary
kallikrein 10 (KLK10) was positively associated with tumor stage progression.
Moreover, the urinary level of KLK10 (uKLK10) was significantly elevated in the
urine of patients with inoperable GC compared to operable GC patients (median,
118 vs. 229; P=0.014). The combination of uKLK10, tumor location and tumor size
distinguished operability of GC with an area under the curve of 0.859, 82.4%
sensitivity and 86.2% specificity. Disease-free survival (DFS) was significantly
shorter in GC patients with high uKLK10 compared to those with low uKLK10 (hazard
ratio: 3.30 [95% confidence interval, 1.58-6.90] P<0.001). Immunohistochemical
analyses also demonstrated a positive correlation between tumor stage and KLK10
expression in GC tissues (r=0.426, P<0.001). In addition, GC patients with high
expression of pathological KLK10 (pKLK10) showed a significantly shorter DFS
compared to those with low pKLK10 (hazard ratio: 3.79 [95% confidence interval,
1.27-11.24] P=0.010). uKLK10 is a promising non-invasive biomarker for the
inoperability and incurability of GC.
PMID- 28418927
TI - Transarterial chemoembolization combined with computed tomography-guided
125iodine implantation enhances survival in hepatocellular carcinoma patients
with portal vein tumor thrombus.
AB - We conducted a retrospective study to evaluate the safety and efficacy of
transarterial chemoembolization (TACE) combined with computed tomography-guided
125iodine implantation (TACE-125iodine) in hepatocellular carcinoma (HCC)
patients with type B portal vein tumor thrombus (PVTT). From medical records, we
determined that 50 patients who received 125iodine implantation 4-7 days after
the first TACE session showed better survival than 50 patients who received only
TACE (median survival, 13.1 vs. 6.0 months; P<0.01). Moreover, the PVTT control
rate was higher in the TACE-125iodine than TACE alone group (78% vs. 18%;
P<0.01). Multivariate analysis demonstrated that the TACE-125iodine procedure was
an independent prognostic factor for overall survival. We also observed that
bilirubin levels were increased at 4 weeks, indicating that 125iodine seeding in
the PVTT beneficially impacted the small bile duct, which is proximal to the
portal vein. No severe adverse events were observed in patients that received
125iodine seed implantation, and the mild adverse events were successfully
treated. This study shows that TACE-125iodine therapy enhances patient survival
with minimal adverse events. It is also more affordable than sorafenib, which is
currently the recommended therapy for advanced HCC patients with PVTT.
PMID- 28418928
TI - ERK signalling modulates epigenome to drive epithelial to mesenchymal transition.
AB - The series of events that allow the conversion from adherent epithelial cells
into migratory cells is collectively known as epithelial-mesenchymal transition
(EMT). EMT is employed during embryonic development such as for gastrulation and
neural crest migration and is misused in diseases, such as cancer metastasis. ERK
signalling is known to be essential for EMT, however its influence on the
epigenetic and transcriptional programme underlying EMT is poorly understood.
Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene
expression in mammary epithelial cells undergoing EMT, we found that ERK
signalling is essential for the epigenetic reprogramming underlying hallmark gene
expression and phenotypic changes of EMT. We show that the chemical inhibition of
Erk signalling during EMT prevents the loss and gain of the H3K27ac mark at
regulatory regions of epithelial and mesenchymal genes, respectively, and results
in a transcriptome and epigenome closer to those of epithelial cells. Further
computational analyses identified a distinct set of transcription factor motifs
enriched at distal regulatory regions that are epigenetically remodelled by ERK
signalling. Altogether, our findings reveal an ERK-dependent epigenetic
remodelling of regulatory elements that results in a gene expression programme
essential for driving EMT.
PMID- 28418929
TI - Plurihormonal cells of normal anterior pituitary: Facts and conclusions.
AB - INTRODUCTION: plurihormonality of pituitary adenomas is an ability of adenoma
cells to produce more than one hormone. After the immunohistochemical analysis
had become a routine part of the morphological study, a great number of adenomas
appeared to be multihormonal in actual practice. We hypothesize that the same
cells of a normal pituitary gland releases several hormones simultaneously.
OBJECTIVE: To analyse a possible co-expression of hormones by the cells of the
normal anterior pituitary of adult humans in autopsy material. MATERIALS AND
METHODS: We studied 10 pituitary glands of 4 women and 6 men with cardiovascular
and oncological diseases. Double staining immunohistochemistry using 11 hormone
combinations was performed in all the cases. These combinations were:
prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH),
prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic
hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH,
TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies
was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin,
TSH/prolactin, ACTH/GH, and FSH/GH. RESULTS: We found that the same cells of the
normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with
ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co
expression coefficients of prolactin, GH and TSH with other hormones showed that
the TSH co-expression coefficient was significantly the least (9,5+/-6,9%; 9,6+/
7,8%; 1,0+/-1,3% correspondingly). CONCLUSION: Plurihormonality of normal
adenohypophysis is an actually existing phenomenon. Identification of different
hormones in pituitary adenomas enables to find new ways to improve both
diagnostic process and targeted treatment.
PMID- 28418930
TI - The innate immunity of guinea pigs against highly pathogenic avian influenza
virus infection.
AB - H5N1 avian influenza viruses are a major pandemic concern. In contrast to the
highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs
do not typically display signs of severe disease in response to H5N1 virus
infection. Here, proteomic and transcriptional profiling were applied to identify
host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002
(H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes
were among host proteins with altered expression in guinea pig lungs during H5N1
infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea
pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was
required for RIG-I mediated inhibition of viral replication upstream of the
activity of MAVS. Furthermore, we show that guinea pig complement is involved in
viral clearance, the regulation of inflammation, and cellular apoptosis during
influenza virus infection of guinea pigs. This work uncovers features of the
guinea pig innate immune response to influenza that may render guinea pigs
resistant to highly pathogenic influenza viruses.
PMID- 28418931
TI - SOCS3 treatment prevents the development of alopecia areata by inhibiting CD8+ T
cell-mediated autoimmune destruction.
AB - Alopecia areata is one of the most common autoimmune diseases resulting from T
cell-mediated damage of hair follicles. CD8+ T cells infiltrate hair follicles
and are responsible for destruction of hair follicles. However the underlying
mechanisms for hair loss remain still obscure. In the present study, we
identified that suppressor of cytokine signaling-3 (SOCS3), a classical inhibitor
of cytokine signaling, significantly inhibits CD8+T cell maturation, interferon
gamma (IFN-gamma) production and alopecia areata. SOCS3 is downregulated in the
skin of alopecia areata patients and murine autoimmune alopecia model.
Furthermore, SOCS3 treatment prevents the development of alopecia areata in the
graft model. SOCS3 decreases the CD44high CD62Llow effector memory CD8+ T cells,
resulting in the decrease of IFN-gamma production. The expression of Fas and
major histocompatibility complex-1 (MHC I) is upregulated in skin from C3H/HeJ
alopecia areata mice, and this increase is suppressed by SOCS3. The SOCS3 level
is negative correlation with the Fas and MHC I level in patients with alopecia
areata. These results suggest that SOCS3 treatment may be an effective strategy
to treat autoimmune alopecia as well as to more generally prevent cytokine
dependent tissue destruction in inflammatory diseases.
PMID- 28418932
TI - BMPR1B mutation causes Pierre Robin sequence.
AB - BACKGROUND: We investigated a large family with Pierre Robin sequence (PRS). AIM
OF THE STUDY: This study aims to determine the genetic cause of PRS. RESULTS: The
reciprocal translocation t(4;6)(q22;p21) was identified to be segregated with PRS
in a three-generation family. Whole-genome sequencing and Sanger sequencing
successfully detected breakpoints in the intragenic regions of BMRP1B and GRM4.
We hypothesized that PRS in this family was caused by (i) haploinsufficiency for
BMPR1B or (ii) a gain of function mechanism mediated by the BMPR1B-GRM4 fusion
gene. In an unrelated family, we identified another BMPR1B-splicing mutation that
co-segregated with PRS. CONCLUSION: We detected two BMPR1B mutations in two
unrelated PRS families, suggesting that BMPR1B disruption is probably a cause of
human PRS. METHODS: GTG banding, comparative genomic hybridization, whole-genome
sequencing, and Sanger sequencing were performed to identify the gene causing
PRS.
PMID- 28418934
TI - Chromosome analysis in a case of a plutonium contaminated wound.
AB - Chromosome analysis of peripheral blood lymphocytes was undertaken over a 10 year
period following an intake of plutonium through a hand wound. Frequencies of
cells with unstable complex aberrations remained high throughout this time,
probably reflecting direct exposure of lymphocytes as they passed plutonium which
had transferred to regional lymph nodes. Analysis at the final sampling time also
revealed cells with stable aberrations at a much higher frequency relative to the
number of unstable cells than expected from direct exposure, and is therefore
most likely to be reflecting exposure to lymphocyte precursor cells from
plutonium that has become deposited on bone surfaces.
PMID- 28418933
TI - Genetic variation of long non-coding RNA TINCR contribute to the susceptibility
and progression of colorectal cancer.
AB - Colorectal cancer (CRC) accounts for the leading causes of cancer-related
morbidity and mortality. However, a large part of heritable factors are warranted
to be explored. Long non-coding RNAs (lncRNAs) serve critical roles in cancer
development and progression. Herein, we explored effect of genetic variants of
Tissue differentiation-inducing non-protein coding RNA (TINCR), a key lncRNA
required for somatic tissue differentiation and tumor progression, on risk and
progression of CRC. Three tagSNPs, including rs2288947, rs8105637, and
rs12610531, were evaluated in in a two-stage, case-control study. Two SNPs,
rs2288947 and rs8105637, were significantly associated with susceptibility of CRC
in both stages. When pooled together, the allele G was significantly associated
with 23% decreased risk of CRC (OR=0.77; 95% CI=0.67-0.88; P value = 1.2*10-4)for
SNP rs2288947. While for SNP rs8105637, the allele A was significantly associated
with 22% increased risk of CRC (OR=1.22; 95% CI=1.09-1.37; P value = 6.2*10-4).
The two SNPs were also statistically associated with occurrence of lymph node
metastasis of CRC. The carriers of allele G are less likely to get lymph node
metastasis (OR=0.77; 95% CI=0.63-0.94; P value = 0.011) for rs2288947, and the
carriers of allele A are more likely to get lymph node metastasis (OR=1.22; 95%
CI=1.03-1.43; P value = 0.019) for rs8105637. These results suggest that lncRNA
TINCR polymorphisms may be implicated in the development and progression of CRC.
PMID- 28418935
TI - Aluminum/vacuum multilayer configuration for spatial high-energy electron
shielding via electron return effects induced by magnetic field.
AB - Radiation shielding of high-energy electrons is critical for successful space
missions. However, conventional passive shielding systems exhibit several
limitations, such as heavy configuration, poor shielding ability, and strong
secondary bremsstrahlung radiation. In this work, an aluminum/vacuum multilayer
structure was proposed based on the electron return effects induced by magnetic
field. The shielding property of several configurations was evaluated by using
the Monte Carlo method. Results showed that multilayer systems presented improved
shielding ability to electrons, and less secondary x-ray transmissions than those
of conventional systems. Moreover, the influences of magnetic flux density and
number of layers on the shielding property of multilayer systems were
investigated using a female Chinese hybrid reference phantom based on cumulative
dose. In the case of two aluminum layers, the cumulative dose in a phantom
gradually decreased with increasing magnetic flux density. The maximum decline
rate was found within 0.4-1 Tesla. With increasing layers of configuration, the
cumulative dose decreased and the shielding ability improved. This research
provides effective shielding measures for future space radiation protection in
high-energy electron environments.
PMID- 28418936
TI - Deposition and spatial variation of thoron decay products in a thoron
experimental house using the Direct Thoron Progeny Sensors.
AB - Experiments have been carried out using the deposition-based Direct Thoron
Progeny Sensors (DTPS) in a thoron experimental house. The objective was to study
the thoron decay product characteristics such as the deposition velocities,
spatial variability and dependence on aerosol particle concentrations. Since the
deposition velocity is an important characteristic in the calibration of the
DTPS, it is very important to study its dependence on aerosol concentration in a
controlled environment. At low aerosol concentration (1500 particles/cm3) the
mean effective deposition velocity was measured to be 0.159 +/- 0.045 m h-1; at
high aerosol concentration (30 000 particles/cm3) it decreased to 0.079 +/- 0.009
m h-1. The deposition velocity for the attached fraction of the thoron decay
products did not change with increasing aerosol concentration, showing
measurement results of 0.048 +/- 0.005 m h-1 and 0.043 +/- 0.014 m h-1,
respectively. At low particle concentration, the effective deposition velocity
showed large scattering within the room at different distances from center. The
attached fraction deposition velocity remained uniform at different distances
from the wall. The measurements in the thoron experimental house can be used as a
sensitivity test of the DTPS in an indoor environment with changing aerosol
concentration. The uniform spatial distribution of thoron decay products was
confirmed within the experimental house. This indicates that direct measurement
of thoron decay product concentration should be carried out instead of inferring
it from thoron gas concentration, which is very inhomogeneous within the
experimental house.
PMID- 28418937
TI - Clinical validation of a new wrist continuous noninvasive hemodynamic monitoring
system in comparison with invasive radial artery measurement.
AB - BACKGROUND: An ideal arterial pressure monitoring system for perioperative care
is required to be accurate, noninvasive, continuous, and risk free. Although
several continuous noninvasive arterial pressures (CNAP) are determined on the
finger, a new wrist CNAP monitoring system was developed. This prospective study
was designed as a randomized-controlled trial to assess its validity in
comparison with invasive arterial pressure (IAP) monitoring. PATIENTS AND
METHODS: Sixty patients undergoing elective surgery under general anesthesia were
enrolled. One-side arm in each patient was selected randomly to assess the new
monitoring system placed on the wrist; an arterial catheter for IAP was inserted
at the radial artery in the contralateral arm. The Bland-Altman method for
repeated measurements was used to assess agreement between measurement methods by
the levels of agreement according to the American Association for the Advancement
of Medical Instrumentation standards. RESULTS: A total of 6600 valid pressure
readings were obtained from 60 patients, including 3000 beat data and 3600 pulse
wave data, respectively. The mean differences in wrist CNAP versus IAP for beat
data were as follows: systolic arterial pressure (SAP): -2.09+/-5.39 mmHg; mean
arterial pressure (MAP): 0.27+/-3.64 mmHg; diastolic arterial pressure (DAP): and
2.63+/-6.44 mmHg. For pulse wave data, the mean difference (SD) values were as
follows: SAP: -2.06+/-6.51 mmHg; MAP: 0.50+/-4.36 mmHg; and DAP: 3.06+/-6.81
mmHg. Percentage errors were less than 28.3%. Levels of agreements were detected
to be -12.65-8.47 for SAP, -6.86-7.40 for MAP, and -9.99-15.26 for DAP.
CONCLUSION: The new wrist CNAP monitoring system showed an acceptable agreement
and interchangeability with the IAP.
PMID- 28418938
TI - A Study on Postmortem Wound Dating by Gross and Histopathological Examination of
Abrasions.
AB - INTRODUCTION: Abrasions are the most common blunt force injuries. The precise
dating of injury is extremely important in forensic medicine practice. As we
know, the wound healing occurs in well-orchestrated sequence, consisting of
inflammation, proliferation, and maturation.A study of occurrence of such phases
will help in understanding the sequence of events in wound healing. In this
context, this study of wound dating from gross and microscopic level was taken.
MATERIALS AND METHODS: Postmortem study of wound dating by gross and
histopathological examination of abrasions was carried out in the Department of
Forensic Medicine, in M.S. Ramaiah Medical College. A total of 101 abrasions were
correlated to time frame the occurrence of different gross changes and
microscopic changes that follow the blunt trauma. Abrasions ranging from 0 hour
to a maximum of 45 days were studied. RESULTS: The gross changes of abrasions
were in correlation with the microscopic changes; however, the role of the
comorbid conditions is significant because the results showed variations with
respect to healing process. CONCLUSIONS: This study signifies that, if naked eye
examination is studied along with histopathological examination, the reliability
and accuracy of dating of wound increase. Whenever accurate determination of age
is required, the autopsy surgeon can subject the samples for histopathological
examination and correlate before opining the age of injury.
PMID- 28418939
TI - Exploring the molecular pathogenesis and biomarkers of high risk oral
premalignant lesions on the basis of long noncoding RNA expression profiling by
serial analysis of gene expression.
AB - Oral premalignant lesions (OPLs) have malignant transformation potential, with no
reliable markers available. This study aimed to assess molecular events to
identify biomarkers that can reflect high-risk lesions as predictive factors to
tailor clinical decision for patients on the basis of long noncoding RNAs
(lncRNA) expression profiling by serial analysis of gene expression. The GSE31021
and GSE8127 datasets were downloaded from the Gene Expression Omnibus database.
Differentially expressed genes (DEGs) and lncRNAs were identified using the LIMMA
package in R language. The genes targeted by lncRNAs were predicted among
screened DEGs using Pearson's correlation. Gene ontology function and Kyoto
Encyclopedia of Genes and Genomes pathway analyses were carried out for genes
targeted by lncRNAs using the Database for Annotation, Visualization, and
Integrated Discovery online tool. A total of 674 DEGs and differentially
expressed lncRNAs were screened. Thirty-two interactions of 10 lncRNAs and 524
target genes were predicted. The lncRNA NEAT1 was among the top 10 lncRNAs. The
coregulated target genes RP4-684O24, RP11-283I3, and RP11-350G8 were
significantly enriched in the immune response and mannosyl-oligosaccharide
mannosidase activity. The target genes coregulated by LINC00665 and MIR378D2 were
significantly enriched in the ubiquitin-dependent protein catabolic process,
ubiquitin-protein ligase activity, and neurotrophin signaling. The lncRNA NEAT1
may play an important role in high-risk lesions. The novel lncRNAs and DEGs
identified in OPLs may mediate the immune response and neurotrophin signaling and
show ubiquitin ligase activity. These results improve our understanding of the
molecular pathogenesis of OPLs and identify some potential targets for early
diagnosis of high risk OPLs.
PMID- 28418940
TI - Assessment of the Albumin-Bilirubin (ALBI) Grade as a Prognostic Indicator for
Hepatocellular Carcinoma Patients Treated With Radioembolization.
AB - OBJECTIVE: As the utility of Child-Pugh (C-P) class is limited by the
subjectivity of ascites and encephalopathy, we evaluated a previously established
objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for
yttrium-90 radioembolization (RE) treatment for patients with hepatocellular
carcinoma (HCC). MATERIALS AND METHODS: A total of 117 patients who received RE
for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P
class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS)
according to these 3 criteria was evaluated by Kaplan-Meier survival analysis.
The utilities of C-P class and ALBI grade as prognostic indicators were compared
using the log-rank test. Multivariate Cox regression analysis was performed to
identify additional predictive factors. RESULTS: Patients with ALBI grade 1
(n=49) had superior OS than those with ALBI grade 2 (n=65) (P=0.01). Meanwhile,
no significant difference was observed in OS between C-P class A (n=100) and C-P
class B (n=14) (P=0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was
able to stratify 2 clear and nonoverlapping subgroups with differing OS curves
(P=0.03). Multivariate Cox regression test identified alanine transaminase,
Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic
factors for OS (P<0.10). CONCLUSIONS: ALBI grade as a prognosticator has
demonstrated clear survival discrimination that is superior to C-P class among
HCC patients treated with RE, particularly within the subgroup of C-P class A
patients. ALBI grade is useful for clinicians to make decisions as to whether RE
should be recommended to patients with HCC.
PMID- 28418941
TI - Prenatal fluoxetine modifies the behavioral and hormonal responses to stress in
male mice: role for glucocorticoid insensitivity.
AB - Women with major depressive disorder during pregnancy often use selective
serotonin reuptake inhibitors (SSRIs) antidepressants. These drugs readily cross
the placental barrier and impact the developing fetal brain. Recently, we
reported that prenatal fluoxetine (FLX), an SSRI antidepressant drug, altered
corticosterone and behavioral responses to stress in female mouse offspring. The
present study assessed the effects of prenatal FLX on these responses in males.
The results showed that prenatal FLX significantly augmented the corticosterone
response to acute stress in young prepubescent mice. The corticosterone response
to continuous stress was not affected by prenatal FLX irrespective of age. In
addition, continuous stress reduced general activity, and anxiety-like and
depressive-like behaviors in adult animals prenatally exposed to FLX, but not in
controls. The dexamethasone suppression test showed that prenatal FLX induced a
state of glucocorticoid insensitivity in adult males, indicating that the
negative feedback control of the hypothalamic-pituitary-adrenal axis response to
stress was disrupted. Together, these findings indicate that prenatal FLX altered
hormonal and behavioral responses to stress and suggest a role for the
development of glucocorticoid insensitivity in these effects. These findings may
aid understanding of the limitations and precautions that should be taken in the
use of SSRIs by pregnant women.
PMID- 28418942
TI - Response rate decreasing effects of naloxone during chronic sucrose availability.
AB - Studies in animal models suggest that sugar deprivation following excessive
intake elicits some opioid-like withdrawal signs. In the present study, opioid
like effects of excessive sucrose intake were further characterized in C57BL/6
mice by comparing the effects of the opioid antagonist naloxone on food
reinforced responding before and during sucrose availability and, in parallel
experiments, following chronic morphine administration. Results show that
naloxone produced time-dependent and dose-dependent decreases in operant response
rates after 4 weeks of excessive sucrose consumption, and that these effects were
comparable with those produced by chronic morphine injections. These findings
extend the observation that excessive sucrose consumption may produce opioid-like
withdrawal signs, and suggest that operant assays of withdrawal-suppressed
behaviors may be useful for further study of excessive sucrose consumption.
PMID- 28418943
TI - Loss of control over alcohol seeking in rats depends on individual vulnerability
and duration of alcohol consumption experience.
AB - Alcohol use disorder (AUD) is characterized by excessive alcohol use and
persistent alcohol seeking despite knowledge of its negative consequences.
Importantly, AUD typically develops after chronic excessive alcohol use in a
subgroup of individuals who drink alcohol, suggesting that AUD results from an
interaction between individual vulnerability and prolonged alcohol exposure. The
present study assessed the contribution of prolonged exposure to alcohol and
individual levels of alcohol intake to the development of loss of control over
alcohol seeking in a conditioned suppression model. To investigate the impact of
prolonged alcohol exposure, conditioned suppression of alcohol seeking was
assessed after 2 and 4 months of intermittent alcohol access (IAA) in a subgroup
of rats drinking moderate amounts of alcohol. We observed that suppression of
alcohol seeking was reduced after 4 months compared with 2 months of IAA. The
influence of individual levels of alcohol intake on loss of control over alcohol
seeking was subsequently determined by assessing conditioned suppression in
subgroups of low and high alcohol drinking rats. Unlike the low alcohol drinking
rats, the high alcohol drinking rats showed aversion-resistant alcohol seeking
after 2 months of IAA, although both groups showed comparable levels of
conditioned freezing. These findings show that the development of loss of control
over alcohol seeking, a key characteristic of AUD in humans, is dependent on both
the extent of alcohol exposure and the individual's propensity to consume
alcohol.
PMID- 28418944
TI - The Benefit of Pro Re Nata Antiemetics Provided With Guideline-Consistent
Antiemetics in Delayed Nausea Control.
AB - BACKGROUND: Delayed nausea after chemotherapy remains a symptom of interest.
Clinicians often provide additional and/or pro re nata (p.r.n.) antiemetics with
guideline-consistent antiemetics in an attempt to achieve further symptom
control. Whether the usage of additional and/or p.r.n. antiemetics provide added
benefit remains as a question. OBJECTIVE: The purpose of this study was to
determine the benefit of providing additional antiemetics and/or p.r.n.
antiemetics with guideline-consistent antiemetics in the control of nausea,
functioning, and quality of life (QOL). METHODS: A secondary data analysis of 143
breast cancer patients who received guideline-consistent antiemetics for
anthracycline and cyclophosphamide chemotherapy was conducted. Instruments
included vomiting frequency and nausea intensity items of the Multinational
Association of Supportive Care in Cancer Antiemesis Tool and the European
Organization for Research and Treatment of Cancer Quality of Life Questionnaire
C30. RESULTS: Providing p.r.n. antiemetics alleviated the incidence of
significant nausea (intensity, >=3) in the delayed phase. The experience of
nausea contributed to symptom incidence in the next phase and cycle. The
intensity of delayed nausea demonstrated a moderate negative correlation with
physical and role functioning and global health/QOL. CONCLUSION: Providing
patients with strategies to further control nausea (p.r.n. antiemetics) in
addition to guideline-consistent antiemetics is recommended for practice. Because
the nausea experience contributes to symptom incidence in the next phase and
cycle and because the nausea intensity demonstrated a significant relationship
with function and global health/QOL, proactive supportive approaches are strongly
recommended. IMPLICATIONS FOR PRACTICE: Delayed nausea control may be improved by
adhering to guideline-consistent antiemetics and using p.r.n. antiemetics.
Delayed nausea control would contribute to patients' functioning and QOL.
PMID- 28418945
TI - Tendonitis and Tendon Rupture After Treatment With Rituximab: A Case Series.
AB - CLINICAL DATA: Rituximab is a mouse/human chimeric anti-CD20 IgG1 monoclonal
antibody used to treat cancer and autoimmune conditions. Side effects of
rituximab include fever, rash, cytopenia and hypotension, back pain, arthralgia,
and myalgia. Here, we report on 3 patients who developed moderate to severe
tendonitis after the second infusion of rituximab. THERAPEUTIC CHALLENGE: We
report 3 patients who developed tendonitis after the second infusion of
rituximab. These patients were undergoing treatment for connective tissue
diseases. All 3 patients received 2 rituximab infusions, 2 weeks apart. The 3
cases developed clinical tendonitis that was confirmed by magnetic resonance
imaging in 2 cases. INTERPRETATION: This is the first case series reporting new
onset tendonitis in patients with connective tissue diseases after rituximab
therapy. All 3 cases developed tendonitis 1 week after receiving the second dose
of rituximab. Clinical features of tendonitis resolved 3-4 months in all cases.
The underlying pathogenic mechanism by which rituximab causes tendonitis is not
clear, but tendonitis and tendon rupture have been reported after using other
medications such as quinolones. The tendon damage was progressive leading to
tendon rupture in 1 patient, highlighting the importance of early recognition. It
is plausible that there is a cause-effect relation between tendonitis and
administration of rituximab in our 3 cases, since none of these cases had
previous history of tendonitis; however, more data are needed to confirm this
observation.
PMID- 28418946
TI - A Case of Cyanosis: Dapsone Induced Methemoglobinemia and Coexisting Pulmonary
Embolism.
PMID- 28418947
TI - Sleep-Induced Apraxia of Eyelid Opening.
AB - BACKGROUND: Apraxia of eyelid opening (AEO) primarily has been described as
bilateral loss of volitional ability to open the eyes at certain times and often
associated with neurodegenerative disease. Rarely, it can occur in isolation and
as an idiopathic phenomenon. There are a few reports of unilateral AEO only on
awakening from sleep. We report an additional 11 patients with this unusual
variation of AEO. METHODS: Retrospective, observational case series of patients
collected from 3 separate neuro-ophthalmology practices. RESULTS: All 11 patients
were Caucasian women with a mean age of 59 years (range 35-80 years). All
experienced AEO on awakening from sleep. Eight patients had unilateral AEO, and 3
had bilateral symptoms. The duration of episodes ranged from 3 weeks to several
years. Ten of the patients reported manually elevating the eyelid to open it,
while 1 patient waited for the eyelid to open spontaneously. After initial manual
elevation, all patients reported normal function and position of the eyelids for
the remainder of the day. Seven patients had a history of autoimmune disease.
Slit-lamp and fundus examinations were negative for ocular pathology to explain
the patients' symptoms, and 9 patients had unremarkable brain imaging.
CONCLUSIONS: AEO occurring only on awakening from sleep is a rare entity.
Neuroimaging and extensive laboratory testing are not indicated without
associated neurologic or ocular findings. There may be a Caucasian female
preponderance and autoimmune link in patients with AEO, but further studies are
required.
PMID- 28418948
TI - Optical Coherence Tomography in Neuroretinitis: Epipapillary Infiltrates and
Retinal Folds.
AB - Neuroretinitis is a form of papillitis associated with the delayed onset of an
exudative macular star among other inflammatory ocular findings. We describe 4
patients with neuroretinitis who displayed several distinctive and novel findings
on spectral-domain optical coherence tomography (OCT) that include "epipapillary
infiltrates" and an atypical pattern of inner retinal folds. The recognition of
these findings on OCT may help in the early diagnosis of neuroretinitis.
PMID- 28418949
TI - Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac
Sarcoidosis and Myocarditis.
AB - PURPOSE: The purpose of this study was to compare combined PET/MRI with PET/CT
and cardiac MRI in the evaluation of cardiac sarcoidosis and myocarditis.
METHODS: Ten patients (4 men and 6 women; 56.1 +/- 9.6 years old) were
prospectively enrolled for evaluation of suspected cardiac sarcoidosis or
myocarditis. Written informed consent was obtained. Following administration of
9.9 +/- 0.9 mCi F-FDG, patients underwent standard cardiac PET/CT followed by
combined PET/MRI using a simultaneous 3-T scanner. Cardiac MRI sequences included
ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging.
Myocardial involvement was assessed with separate analysis of combined PET/MRI,
PET/CT, and cardiac MRI data using dedicated postprocessing software. Estimates
of radiation dose were derived from the applied doses of F-FDG and CT protocol
parameters. RESULTS: Imaging was acquired with a delay from F-FDG injection of
90.2 +/- 27.4 minutes for PET/CT and 207.7 +/- 40.3 minutes for PET/MRI. Total
scan time for PET/MRI was significantly longer than for PET/CT (81.4 +/- 14.8 vs
12.0 minutes, P < 0.001). Total effective radiation dose was significantly lower
for PET/MRI compared with PET/CT (6.9 +/- 0.6 vs 8.2 +/- 1.1 mSv, P = 0.007).
There was no significant difference in the number of positive cases identified
between combined PET/MRI (n = 10 [100%]), PET/CT (n = 6 [60%]), and cardiac MRI
(n = 8 [80%]), P = 0.091. CONCLUSIONS: Simultaneous cardiac PET/MRI is feasible
in the evaluation of cardiac sarcoidosis and myocarditis achieving diagnostic
image quality.
PMID- 28418950
TI - Sacral Fatigue Fracture in a Military Recruit.
AB - A 19-year-old male military recruit presented with 3 weeks of persistent left hip
and groin pain after abnormally twisting his hip during a hike. Initial
radiographs were interpreted as negative. He subsequently underwent a bone scan
which revealed linear left sacral uptake along or paralleling the sacroiliac
joint. Differential diagnostic considerations included unilateral sacroiliitis
and sacral fracture. SPECT/CT was performed which confirmed left sacral fatigue
stress fracture. Transitional lumbosacral anatomy was evident on radiographs with
pseudoarticulation of the transitional left S1 transverse process with the
sacrum. We postulate this predisposed the recruit to sacral fracture.
PMID- 28418951
TI - Putaminal Hypometabolism Exceeding Caudate Abnormalities on 18F-FDG PET in
Huntington Disease.
AB - An F-FDG PET scan performed on a patient suspected of having early Huntington
disease (HD) showed marked hypometabolism in bilateral putamen that was
significantly worse than the hypometabolism in caudate. While HD could not be
completely excluded, the scan finding was felt to be somewhat atypical for HD
because of a lesser degree of caudate involvement. Genetic testing eventually
confirmed the diagnosis of HD. This case shows that diagnosis of HD should still
be considered even when putaminal hypometabolism exceeds caudate? changes on F
FDG PET imaging.
PMID- 28418952
TI - FDG PET/CT Findings of Nodular Sclerosis-Subtype Classic Hodgkin Lymphoma
Presented as Mediastinal Nodal Lesions at Onset But as Predominant Osseous
Disease at Relapse.
AB - Nodular sclerosis-subtype classic Hodgkin lymphoma in general manifests as bulky
mediastinal lymphadenopathy but very rarely involves bones. We report FDG PET/CT
findings of a 19-year-old man with pathology-proven, nodular sclerosis-type
classic Hodgkin lymphoma. His initial FDG PET/CT scan at the diagnosis showed
only hypermetabolic lymphadenopathy in the mediastinum. However, the FDG PET/CT
acquired when the disease recurred 20 months later showed predominant osseous
disease without additional nodal lesions outside the mediastinum.
PMID- 28418953
TI - Pulmonary Perfusion Scan Mimicking Hepatobiliary Scintigraphy in a Patient With
an Uncommon Manifestation of Granulomatosis With Polyangiitis.
AB - A 36-year-old man with known granulomatosis with polyangiitis underwent
quantitative ventilation-perfusion pulmonary scintigraphy as part of an initial
evaluation for lung transplant candidacy. Radiotracer uptake on the perfusion
study has the appearance of the hepatic silhouette, drawing initial concern that
there may have been a misadministration of Tc with a hepatobiliary agent.
Comparison CT reveals extensive cystic bronchiectasis, parenchymal destruction,
and volume loss involving the entire left lung and basal portions of the right
lung, with the residual portions of functional lung parenchyma conforming to a
shape similar to the liver.
PMID- 28418954
TI - Aortic Root Abscess Clearly Shown on 111In-Leukocyte Scan But Less Obvious on
Transesophageal Echocardiogram.
AB - A 79-year-old man with history of aortic stenosis, status post bioprosthetic
aortic valve replacement, episodes of bacteremia, and endocarditis presented to
hospital with fever. Clinical assessment led to suspicion of possible
endocarditis. Initial interpretation of transesophageal echocardiogram was
inconclusive without vegetation in mitral/aortic valve. An In-leukocyte scan
demonstrated increased uptake in the area of aortic valve, suggestive of
infection. Further review of the transesophageal echocardiogram showed signs of
annular abscess. This case highlights that combination of echocardiography with
white blood cell imaging increases the sensitivity to detect
endocarditis/perivalvular abscess.
PMID- 28418955
TI - Late 124I PET/CT Uptake Measurement-Assessment of Appropriate Examination
Protocol in Benign Thyroid Diseases.
AB - PURPOSE: This study aimed at investigating the performance of late I PET/CT for
radioiodine uptake (RAIU) measurement at 336 hours after administration in
patients with benign thyroid diseases requiring radioiodine therapy. Special
attention was paid to the comparability of I uptake (I-RAIU) to the clinical
standard (I-RAIU, probe measurement). Considering cost aspects, we sought to
establish an economically reasonable examination protocol based on scan duration
and administered activity. METHODS: List-mode PET data sets of 40-minute
acquisition time were acquired 336 hours after administration of 1 MBq I in 18
patients. Different scan durations were simulated by different reconstruction
intervals (RIs) ranging from 5 seconds to 40 minutes, and total thyroid activity
was measured. Mean I-RAIU levels of each RI were compared with mean I-RAIU levels
(3 MBq). A hypothetical scan duration or hypothetical activity, respectively, was
sought by means of a proportion equation, considering that the length of an RI is
equitable to a hypothetical activity. RESULTS: After 336 hours, the mean total
thyroid activity was 254 +/- 7.7 kBq for I and 26.9 +/- 8.7 kBq for I. The mean I
RAIU and I-RAIU showed high levels of agreement for RI from 2 minutes to 40
minutes. Reconstruction interval shorter than 2 minutes did not result in
sufficient agreement. CONCLUSIONS: The present study confirmed the feasibility of
late I PET/CT as alternative method for RAIU measurement in patients with benign
thyroid diseases; 1 MBq I PET/CT scans as short as 2 minutes resulted in RAIU
levels comparable to those of standard I-RAIU. The parameter "appropriate scan
duration activity product" is proposed to enable an economically reasonable
examination protocol.
PMID- 28418957
TI - Withholding, Withdrawing or Not Analyzing Data: Can Researchers Allow Data to be
Silent?
PMID- 28418958
TI - To Improve Cancer Treatment, We Need to Have Patients and Care Teams Connected!
PMID- 28418966
TI - Clinical Effectiveness and Safety of Intraoperative Methadone in Patients
Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded,
Controlled Trial.
AB - BACKGROUND: Patients undergoing spinal fusion surgery often experience severe
pain during the first three postoperative days. The aim of this parallel-group
randomized trial was to assess the effect of the long-duration opioid methadone
on postoperative analgesic requirements, pain scores, and patient satisfaction
after complex spine surgery. METHODS: One hundred twenty patients were randomized
to receive either methadone 0.2 mg/kg at the start of surgery or hydromorphone 2
mg at surgical closure. Anesthetic care was standardized, and clinicians were
blinded to group assignment. The primary outcome was intravenous hydromorphone
consumption on postoperative day 1. Pain scores and satisfaction with pain
management were measured at postanesthesia care unit admission, 1 and 2 h
postadmission, and on the mornings and afternoons of postoperative days 1 to 3.
RESULTS: One hundred fifteen patients were included in the analysis. Median
hydromorphone use was reduced in the methadone group not only on postoperative
day 1 (4.56 vs. 9.90 mg) but also on postoperative days 2 (0.60 vs. 3.15 mg) and
3 (0 vs. 0.4 mg; all P< 0.001). Pain scores at rest, with movement, and with
coughing were less in the methadone group at 21 of 27 assessments (all P = 0.001
to < 0.0001). Overall satisfaction with pain management was higher in the
methadone group than in the hydromorphone group until the morning of
postoperative day 3 (all P = 0.001 to < 0.0001). CONCLUSIONS: Intraoperative
methadone administration reduced postoperative opioid requirements, decreased
pain scores, and improved patient satisfaction with pain management.
PMID- 28418971
TI - Preanesthetic Assessment Clinic: Early Beginnings in the Bronx.
PMID- 28418972
TI - In Reply.
PMID- 28418973
TI - Rapid Fluid Infusion and Depth of Anesthesia.
PMID- 28418974
TI - In Reply.
PMID- 28418975
TI - Front of Neck Airway: The Importance of the Correct (Obese) Models and (Trained)
Participants in Study Design.
PMID- 28418976
TI - In Reply.
PMID- 28418977
TI - You Have a Plan B. Should You Have a Plan C?
PMID- 28418978
TI - In Reply.
PMID- 28418979
TI - Percutaneous Aponeurotomy and Lipofilling (PALF) versus Limited Fasciectomy in
Patients with Primary Dupuytren's Contracture: A Prospective, Randomized,
Controlled Trial.
PMID- 28418980
TI - Hemodynamic Study of Three Patterns of Flaps on Rats with a Novel Panoramic
Photographing Technique Involved.
PMID- 28418981
TI - Reply: Percutaneous Aponeurotomy and Lipofilling (PALF) versus Limited
Fasciectomy in Patients with Primary Dupuytren's Contracture: A Prospective,
Randomized, Controlled Trial.
PMID- 28418982
TI - Reply: Effectiveness of Autologous Fat Grafting in Adherent Scars: Results
Obtained by a Comprehensive Scar Evaluation Protocol.
PMID- 28418983
TI - Effectiveness of Autologous Fat Grafting in Adherent Scars: Results Obtained by a
Comprehensive Scar Evaluation Protocol.
PMID- 28418984
TI - Short article: Anger and quality of life in patients co-infected with HIV and
hepatitis C virus: a cross-sectional study (ANRS CO13-HEPAVIH).
AB - OBJECTIVE: The aim of this study is to document the relationship between anger
dimensions (state, trait, expression, and control) and quality of life (QoL) in
patients co-infected with HIV and hepatitis C virus (HCV). PATIENTS AND METHODS:
This is a cross-sectional study nested in the ANRS CO13-HEPAVIH French national
cohort. Anger and QoL were assessed using self-administered questionnaires in 536
HIV-HCV-co-infected patients. Correlations between anger scores (STAXI-2 scale)
and QoL scores (WHOQOL-HIV BREF scale) were assessed using Spearman's
coefficients. Multiple linear regression models were then used to test the
relationship between the different dimensions of anger and QoL after adjustment
for statistically significant psychosocial, sociobehavioral, and clinical
characteristics. RESULTS: Patients with excessive alcohol use or history of
injecting drug use had higher levels of anger. All dimensions of anger were
significantly correlated with impaired QoL for all six dimensions of the WHOQOL
HIV BREF scale. Greater internal experience of anger and impaired anger control
were confirmed as independent correlates of impaired QoL related to psychological
health, social relationships, and patients' beliefs after adjustment for
depressive symptoms, functional impact of fatigue, socioeconomic status, and HIV
related characteristics. CONCLUSION: Anger issues need close monitoring in HIV
HCV-co-infected patients, especially in patients with addictive behaviors.
Screening for problems in anger management and implementing individualized
psychotherapeutic strategies may help improve QoL in this population.
PMID- 28418985
TI - It's time to ponder.
PMID- 28418986
TI - Performance of Virological Testing for Early Infant Diagnosis: A Systematic
Review.
AB - BACKGROUND: Improved access to both maternal antiretroviral therapy and infant
prophylaxis may have an impact on the performance of virological assays for
diagnosis of HIV infection in infants. This systematic review was performed to
assess the diagnostic accuracy of virological testing at birth as well as the
performance of virological testing on dried blood spots at 6 weeks among HIV- and
antiretroviral (ARV)-exposed infants. METHODS: A systematic review was performed
for studies published between January 1, 2009 and January 30, 2015. The search
strategy included studies related to HIV, nucleic acid amplification tests, and
newborns/infants and queried PubMed, Embase, the Cochrane Library, LILACS as well
as several conference proceedings. Two independent reviewers collected studies
and extracted data. The final analysis includes summary estimates of the
sensitivities and specificities of the virological assays assessed. The GRADE
approach was used to assess the overall quality of evidence and Quality
Assessment of Diagnostic Accuracy Studies was used to evaluate the risk of bias
in the studies. RESULTS: A total of 2243 records were screened with a final
selection of 5 manuscripts. To assess the test characteristics of virological
testing at birth, 2 studies were used to calculate a pooled sensitivity of 69.3%
(95% confidence interval: 61.1 to 77.4) and a specificity of 99.9% (98.6-100%).
The quality of evidence to support the sensitivity of assays at birth was low,
whereas the quality of evidence for the specificity of such tests was
intermediate-high. In terms of the performance of virological testing on dried
blood spots for HIV- and ARV-exposed infants, 3 studies were used to calculate a
pooled sensitivity of 99.4% (98.3-100.00%) and specificity of 99.6% (99.1
100.00%). The quality of evidence for both outcomes was low. CONCLUSION: The
performance of polymerase chain reaction at birth demonstrates low sensitivity
and high specificity, reflecting the difficulty of detecting intrapartum
infections at birth and transmission dynamics. In addition, there is no evidence
to suggest poor performance of virological testing on dried blood spots for ARV
exposed infants. Overall, given the very limited and low-quality evidence,
further research is needed to assess the accuracy of polymerase chain reaction at
different time points and in the context of more effective prevention of mother
to-child transmission interventions.
PMID- 28418987
TI - The Roles of Behavioral and Social Science Research in the Fight Against
HIV/AIDS: A Functional Framework.
AB - Landmark advances have been made in HIV/AIDS prevention and treatment. These
include proof-of-concept and public health implementation of preexposure
prophylaxis and "treatment as prevention" to reduce HIV transmission as well as
definitive evidence of the clinical gain from early antiretroviral treatment
initiation. Significant progress has been made in understanding and addressing
the social contexts and behavioral factors that impact HIV prevention, care, and
treatment interventions. These include facilitating uptake of testing and
counseling, developing technology-based interventions that increase viral
suppression, reducing HIV/AIDS-related stigma, and addressing other
sociobehavioral and structural barriers to care and treatment. This evolving
landscape provides an important juncture to assess current and future directions
for HIV/AIDS behavioral and social science research (BSSR). We propose a
functional framework for HIV/AIDS-related BSSR, highlighting 4 primary BSSR
domains: (1) understanding vulnerable populations and contexts of risk ("Basic
BSSR"); (2) improving behavioral and social factor approaches to risk reduction,
prevention, and care ("Elemental BSSR"); (3) strengthening the design and
outcomes of biomedically focused research in HIV/AIDS treatment and prevention
("Supportive BSSR"); and (4) contributing building blocks to integrated HIV/AIDS
prevention and treatment approaches ("Integrative BSSR"). These domains and their
resulting confluence at the highest level underscore how fundamental and
essential BSSR is to current and future efforts to prevent, treat, and cure
HIV/AIDS.
PMID- 28418988
TI - HIV-Specific CD8 T Cells Producing CCL-4 Are Associated With Worse Immune
Reconstitution During Chronic Infection.
AB - BACKGROUND: Immunological nonresponse represents the Achilles heel in the
combination antiretroviral therapy (cART) effectiveness, and increases risk of
clinical events and death. CD8 T cells play a crucial role in controlling HIV
replication, and polyfunctional HIV-specific CD8 T cells have been associated
with nonprogressive HIV infection. However, the possible role of polyfunctional
CD8 T cells in predicting posttreatment immune reconstitution has not yet been
explored. The aim of this study was to identify functional markers predictive of
immunological response to cART in chronic HIV-infected patients. METHODS: A
cohort of chronic HIV-infected individuals naive to cART were enrolled in the
ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as
susceptibility to apoptosis were analyzed before and after 12 months of cART.
Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was
also assessed. RESULTS: Results showed a significant correlation between worse
CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of
effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells
all before cART. Moreover, CD8 functional subsets expressing total C-C motif
chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma
(IFNgamma) were negatively associated with immune reconstitution. CONCLUSIONS: In
conclusion, our study shows that a more differentiated phenotype of CD4 T cells
and CCL-4-producing CD8 T cells could represent valuable predictors of worse
immune reconstitution. These parameters may be used as tools for identifying
patients at risk of immunological failure during cART and eventually represent
the basis for innovative therapeutic strategies.
PMID- 28418989
TI - Impact of Antiretroviral Treatment Containing Tenofovir Difumarate on the
Telomere Length of Aviremic HIV-Infected Patients.
AB - OBJECTIVE: To evaluate the in vivo relevance of the inhibitory effect of
tenofovir on telomerase activity observed in vitro. DESIGN: Cross-sectional study
of HIV-infected patients with suppressed virological replication (HIV RNA <50
copies/mL for more than 1 year). METHODS: Telomere length in whole blood was
measured by quantitative real-time polymerase chain reaction. We performed a
multivariate analysis to elucidate variables associated with telomere length and
also evaluated the association between telomere length and use of tenofovir
difumarate (TDF) adjusted by significant confounders. RESULTS: 200 patients
included, 72% men, median age 49 (IQR 45-54.5), 103 with exposure to a TDF
containing antiretroviral treatment (ART) regimen (69.9% for more than 5 years)
and 97 never exposed to a TDF containing ART regimen. In the multivariate
analysis, significant predictors of shorter telomere length were older age (P =
0.008), parental age at birth (P = 0.038), white race (P = 0.048), and longer
time of known HIV infection (10-20 and >=20 years compared with <10 years, P =
0.003 and P = 0.056, respectively). There was no association between TDF exposure
and telomere length after adjusting for possible confounding factors (age,
parental age at birth, race, and time of HIV infection). Total time receiving ART
and duration of treatment with nucleoside reverse transcriptase inhibitors were
associated with shorter telomere length, but these associations were explained by
time of known HIV infection. CONCLUSIONS: Our data do not suggest that telomerase
activity inhibition caused by TDF in vitro leads to telomere shortening in
peripheral blood of HIV-infected patients.
PMID- 28418990
TI - Bone Density, Microarchitecture, and Tissue Quality After Long-Term Treatment
With Tenofovir/Emtricitabine or Abacavir/Lamivudine.
AB - OBJECTIVES: HIV infection has been associated with reduced bone mineral density
(BMD). Antiretroviral therapy (ART) has a deleterious effect on BMD, but its
effect on bone fragility is not clear. The objective of this study is to analyze
the BMD, microarchitecture, and tissue quality of bone in patients receiving long
term tenofovir- or abacavir-based ART. DESIGN: We conducted a cross-sectional
study in patients with HIV undergoing tenofovir or abacavir ART for more than 5
years. METHODS: We measured BMD using dual X-ray absorptiometry ,bone
michroarchitecture using trabecular bone score (TBS), and bone tissue quality
using microindentation. TBS is a dual X-ray absorptiometry-based software that is
more highly correlated with bone fragility than BMD. Microindentation (BMSi)
directly assesses bone quality at the tissue level. RESULTS: A total of 63
patients were included in this study, with 36 belonging to the TDF-FTC group and
27 to the ABC-3TC group. Patients receiving TDF-FTC treatment showed lower BMD
values than those in the ABC-3TC group. We found no differences in TBS or
microindentation between the 2 groups. However, after adjusting for sex, age,
body mass index, and 25[OH]vitD we found lower BMSi and thus poorer bone
properties in the TDF-FTC group than in the ABC-3TC group [beta coefficient
3.594 (confidence interval: 95% -0.12 to -7.61); P = 0.043]. CONCLUSIONS: Long
term treatment with TDF-FTC leads to impaired bone health, not only in terms of
BMD but also in terms of bone quality, another determinant of overall bone
strength. To complement BMD-based predictions, these other techniques may also be
used to identify patients with excess fracture risk.
PMID- 28418991
TI - Effect of Legal Status on the Early Treatment Outcomes of Migrants Beginning
Combined Antiretroviral Therapy at an Outpatient Clinic in Milan, Italy.
AB - OBJECTIVE: In a setting of free access to HIV care, we compared the early
treatment outcomes of HIV-infected undocumented migrants (UMs), documented
migrants (DMs), and Italian subjects. METHODS: The clinical data of 640 Italians
and 245 migrants who started combined antiretroviral therapy (cART) at an HIV
clinic in Milan, Italy, were reviewed. The migrants were mainly Latin Americans
(83 DMs and 56 UMs) or sub-Saharan Africans (52 DMs and 11 UMs), but a minority
were of other origin (33 DMs and 10 UMs). Retention in follow-up and HIV
suppression were compared between UMs, DMs, and natives 12 months +/- 90 days
after start of cART. RESULTS: There were no significant between-group differences
in the stage of HIV infection at the start of cART or the type of regimen
received. The Latin American DMs and UMs included a higher proportion of
transgender women than the other ethnic groups (P < 0.001). The UMs were less
frequently followed up after 12 months than the DMs and natives (P = 0.004) and
were more frequently permanently lost to follow-up (P < 0.001). UM status was an
independent predictor of lost to follow-up (adjusted odds ratio 8.05, P < 0.001).
The DMs and UMs were less frequently HIV suppressed after 12 months than the
natives (78% and 80.7% vs 90.5%, P = 0.001), and Latin American migrants were
significantly less likely to be virologically suppressed than the natives
(adjusted odds ratio 0.30, P = 0.001). CONCLUSIONS: Despite their free access to
cART, subgroups of migrants facing multiple levels of vulnerability still have
difficulties in gaining optimal HIV care.
PMID- 28418992
TI - Initiation of Antiretroviral Therapy Containing Integrase Inhibitors Increases
the Risk of IRIS Requiring Hospitalization.
PMID- 28418993
TI - Solid Papillary Breast Carcinomas Resembling the Tall Cell Variant of Papillary
Thyroid Neoplasms: A Unique Invasive Tumor With Indolent Behavior.
AB - Thirteen cases of invasive solid papillary breast carcinomas resembling the tall
cell variant of papillary thyroid neoplasms (BPTC) are reported here. Some cases
had long-term follow-up. BPTC is a special type of primary breast neoplasm
showing a triple-negative profile but low aggressive potential. Knowledge on BPTC
is still scanty; therefore, the aim of the present paper was to report on the
features of an additional 13 cases. All the patients were female individuals, and
the mean age at presentation was 62.6 years; nodule sizes ranged from 0.6 to 2.5
cm (average, 1.6 cm). All the cases were characterized on histology by papillary,
follicular as well as solid structures. The cells were columnar, eosinophilic
mostly with granular cytoplasms, rich in mitochondria, with the features of
oncocytes in no fewer than 7 cases. Estrogen and progesterone receptors as well
as HER2 were consistently negative. The Ki67 proliferative index was low. Markers
consistent with thyroid origin, such as TTF1 and thyroglobulin, were negative.
Five cases stained for mammoglobin and GATA 3 were positive. All cases proved to
be invasive and 2 cases each experienced metastases to 1 lymph node (axillary and
intramammary). One case of the latter had a local recurrence. Nevertheless, all
the patients are alive, free of disease 24 to 132 months after surgery, of which
8 are without further treatment The present series confirms that BPTC is a
primary breast tumor of low malignant potential.
PMID- 28418994
TI - Clinicopathologic Association and Prognostic Value of Microcystic, Elongated, and
Fragmented (MELF) Pattern in Endometrial Endometrioid Carcinoma.
AB - Microcystic, elongated, and fragmented (MELF) pattern is seen in the invasive
front of some endometrial endometrioid carcinomas. Although MELF pattern can be
expected as an indicator of patient outcomes, its prognostic significance remains
unclear. This study was conducted to elucidate clinicopathologic features and the
prognostic impact of MELF pattern in patients with endometrial endometrioid
carcinoma. We retrospectively analyzed data of 479 consecutive patients with
endometrial endometrioid carcinoma that had been surgically resected. In 45 of
427 patients (11%) with low-grade endometrioid carcinoma, MELF pattern was found,
but it was found in none of the 52 patients with high-grade endometrioid
carcinoma. Among the patients with low-grade endometrioid carcinoma, MELF pattern
was associated significantly with larger tumor size, myometrial invasion of more
than 50%, advanced International Federation of Gynecology and Obstetrics stages,
lymphovascular space invasion, lymph node metastasis, papillary architecture, and
mucinous differentiation. However, survival analysis revealed that the patients
with MELF pattern showed no significantly worse prognosis than those without MELF
pattern either in disease-specific survival or in recurrence-free survival. MELF
was not a significant prognosticator after adjustment for International
Federation of Gynecology and Obstetrics stage (disease-specific survival [hazard
ratio, 1.47; 95% confidence interval, 0.28-7.67; P=0.64], recurrence-free
survival [hazard ratio, 0.98, 95% confidence interval, 0.32-2.99, P=0.98]).
Immunohistochemical analysis revealed that MELF pattern was positive for p16 and
p21 and almost negative for Ki-67 labeling, which suggested that tumor cells in
MELF pattern were involved in growth arrest or cellular senescence. We conclude
that MELF pattern could have little impact on outcomes of patients with low-grade
endometrial endometrioid carcinoma.
PMID- 28418995
TI - Kidney Biopsy Yield: An Examination of Influencing Factors.
AB - Kidney biopsies are conducted under varying scenarios, presenting variables that
could potentially influence yield and adequacy of tissue collected. We
retrospectively reviewed 636 native and allograft kidney biopsies, and compared
tissue collected between differing practitioners performing the biopsy
(nephrologists or radiologists), imaging modalities for guidance (ultrasound or
computed tomography), gauge needle used (18 or 16 G), and between on-site
evaluators of biopsy adequacy conducted at the time of biopsy (general
pathologists, renal pathologists, nephrologists). For radiologists using
ultrasound guidance and 18 G needles, those using on-site evaluation of adequacy
collected more glomeruli and glomeruli per length of tissue core than those not
using on-site evaluation. Radiologists not using on-site evaluation but who used
a larger bore needle (16 vs. 18 G) could generally collect comparable tissue as
other biopsy performers who used on-site evaluation. Radiologists performing
ultrasound-guided biopsies with 18 G needles without on-site evaluation
consistently provided poorer tissue yield and had a higher rate of providing
insufficient tissue so that a diagnosis could not be rendered. Nephrologists
collected less total length of tissue cores, glomeruli, and arteries per case
(whether performing the biopsy and/or performing on-site adequacy) compared with
other groups using on-site evaluation, however, providing comparable density of
glomeruli and arteries. Complication rates did not differ between compared groups
using 18 G needles. It is our observation that the various conditions by which a
kidney biopsy is obtained influences the yield of tissue collected and the
subsequent ability for a pathologist to effectively provide a diagnosis.
PMID- 28418996
TI - Mobilizing Immune Cells With Exercise for Cancer Immunotherapy.
AB - Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy
are effective in treating blood cancers and posttransplant infections, but low
circulating cell numbers in patients and donors are oftentimes a limiting factor.
We postulate that a single exercise bout will increase the yield of patient- and
donor-derived HSCs and cytotoxic lymphocytes to improve this form of treatment
for cancer patients.
PMID- 28418997
TI - Exercise Is Medicine, But Does It Interfere With Medicine?
AB - Exercise frequently is prescribed therapeutically, either on its own or combined
with drugs. A drug's absorption, distribution, metabolism, and excretion can be
affected by the user's anatomy and physiology, which are both changed by the
myriad of complex adaptations to acute and chronic exercise. This article reviews
the research that suggests exercise may influence a drug's plasma concentration,
and thus its efficacy and safety.
PMID- 28418999
TI - Interval Walking Training Can Increase Physical Fitness in Middle-Aged and Older
People.
AB - No long-term exercise training regimen with high adherence and effectiveness for
middle-aged and older individuals is currently broadly available in the field. To
address this problem, we developed an exercise training system comprising
interval walking training and an information technology network that requires
only minimal staff support. We hypothesized that our training system could
increase physical fitness in older people.
PMID- 28418998
TI - Physical Activity as Cause and Cure of Muscular Pain: Evidence of Underlying
Mechanisms.
AB - Work-related physical activity (PA), in terms of peak loads and sustained and/or
repetitive contractions, presents risk factors for the development of muscular
pain and disorders. However, PA as a training tailored to the employee's work
exposure, health, and physical capacity offers prevention and rehabilitation. We
suggest the concept of "Intelligent Physical Exercise Training" relying on
evidence-based sports science training principles.
PMID- 28419001
TI - New Insights Into the Impact of Dehydration on Blood Flow and Metabolism During
Exercise.
AB - Exercise-induced dehydration can lead to impaired perfusion to multiple regional
tissues and organs. We propose that the impact of dehydration on regional blood
flow and metabolism is dependent on the extent of the cardiovascular demand
imposed by exercise, with the greatest physiological strain seen when approaching
cardiovascular and aerobic capacities.
PMID- 28419000
TI - Exercise-Induced Autophagy in Fatty Liver Disease.
AB - Hepatic steatosis prevails each year. Autophagy is integral in mitochondrial
quality control and lipid homeostasis in the liver. No pharmacological strategies
are currently available to reduce hepatic steatosis, but exercise has been known
to improve clinical outcomes of chronic liver disease, particularly nonalcoholic
fatty liver disease (NAFLD). Recent studies suggest that exercise may improve
NAFLD through enhancing autophagy.
PMID- 28419002
TI - Skeletal Muscle Remodeling: Interconnections Between Stem Cells and Protein
Turnover.
AB - Nutrition and exercise are important components of a healthy lifestyle to improve
rates of hypertrophic and nonhypertrophic skeletal muscle remodeling. We provide
evidence to support the hypothesis that muscle stem cells and protein turnover
are collaborative, not separate, mechanisms supporting muscle remodeling by
facilitating protein, nuclear, and cellular turnover in response to the ingestion
of protein dense foods and exercise.
PMID- 28419004
TI - Small Sample Sizes Confound Understanding of Cardiometabolic Responses to
Exercise.
AB - Considerable variability exists in the cardiometabolic disease biomarker response
to exercise. We propose that a major contributor to this heterogeneity is
underpowered studies due to small sample sizes. To test our hypothesis, we
conducted a systematic review to identify meta-analyses/reviews of randomized
controlled trials (RCT) and RCT that examined the cardiometabolic disease
biomarker response to aerobic and resistance exercise.
PMID- 28419005
TI - Clinical Utility of Polymerase Chain Reaction Testing for Streptococcus
pneumoniae in Pediatric Cerebrospinal Fluid Samples: A Diagnostic Accuracy Study
of More Than 2000 Samples From 2004 to 2015.
AB - The aim of this retrospective study was to review the diagnostic accuracy of real
time polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) samples
for Streptococcus pneumoniae DNA in comparison with traditional bacterial
culture. The hypothesis was that PCR is more sensitive than culture and would
detect more cases of pneumococcal meningitis, particularly in children treated
with antimicrobials before CSF sampling occurred. Patients younger than 16 years
of age who had a CSF sample tested for S. pneumoniae DNA by PCR between 2004 and
2015 were included. A total of 2025 samples were included, and the PCR had a
sensitivity of 100% and specificity of 98% for the detection of S. pneumoniae DNA
in comparison with culture. Of the 28 culture negative/PCR positive cases, 25
(89%) were probable meningitis cases and only 3 (11%) were suspected false
positive results. Nineteen (76%) of the 25 probable cases required ICU admission,
and 3 died (12%). Six different serotypes were found in the culture positive
patients (18C, 6B, 14, 22F, 7F and 33F). This study demonstrates that PCR testing
of CSF samples for S. pneumoniae is sensitive and specific when compared with
culture. PCR is particularly useful in detecting those cases where culture is
negative, perhaps relating to pre-CSF sampling administration of antimicrobials.
PMID- 28419006
TI - Plasma Interferon-Gamma-Inducible Protein 10 Level Associates With Abnormal
Memory B Cells Phenotypes in Perinatal HIV Infection.
AB - We demonstrate for perinatally HIV-infected children and adolescents receiving
combined antiretroviral therapy and in good clinical status with respect to HIV
disease that high concentrations of interferon-gamma-inducible protein 10
associate with increased exhausted memory B cells.
PMID- 28419008
TI - Protection Is Key in a Risky Business.
PMID- 28419007
TI - Persistence of Hepatitis B Immunity Following 3-dose Infant Primary Series in HIV
infected Thai Adolescents and Immunologic Response to Revaccination.
AB - BACKGROUND: HIV infection may alter immunologic response and the establishment of
immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to
determine the need to revaccinate perinatally HIV-infected Thai adolescents.
METHODS: Cross-sectional serologic tests for HBV, including hepatitis B surface
antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core
antibody (anti-HBc), were performed in perinatally HIV-infected adolescents.
Adolescents having anti-HBs <100 mIU/mL with negative anti-HBc and immune
reconstitution from highly active antiretroviral therapy (HAART) were
revaccinated using regular (10 MUg) 3-dose schedule given intramuscularly at 0-,
2- and 6-month intervals. RESULTS: Of 193 adolescents who received 3-dose infant
HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile
range) current age 14.5 (11.7-16.2) years, 7 (3.6%) had positive anti-HBc
(indicating breakthrough infection), of which 4 (2%) had positive hepatitis B
surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents
had protective anti-HBs concentration >10 mIU/mL. Of 164 revaccinated
adolescents, 142 (86.6%) had HIV viral load <40 copies/mL. Anti-HBs
seroconversion rates >10 mIU/mL were 58.0% (94/162) after the first dose and
97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects
responded to the first dose with anti-HBs antibody >=100 mIU/mL had a shorter
median duration with CD4 count <15% than their counterparts (6.2 vs. 11.1 months;
P = 0.049). CONCLUSIONS: Only half of perinatally HIV-infected adolescents were
able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination
with 3-dose schedule is required in perinatally HIV-infected adolescents who did
not initiate HAART at the time of infant vaccination.
PMID- 28419009
TI - Working Together to Educate and Safeguard You.
PMID- 28419010
TI - Extending Short Peripheral Catheter Dwell Time: A Best Practice Discussion.
AB - Complications involving short peripheral catheters (SPCs) can significantly
affect health care costs, patient quality of life, morbidity, mortality, and
treatment expense, especially when the hospital stay is lengthened. This article
examines the relationship between SPC dwell time and the incidence of phlebitis
and potential bacteremia. The literature is replete with most studies supporting
SPCs remaining in situ until a clinical reason warrants catheter removal.
Removing and not routinely restarting unneccessary intravenous catheters can help
prevent catheter-related infections and other vascular complications and reduce
cost.
PMID- 28419011
TI - Establishing a Dedicated Difficult Vascular Access Team in the Emergency
Department: A Needs Assessment.
AB - Peripheral vascular access is one of the most common procedures performed in
emergency departments across the United States. Successful venipuncture is
critical in providing timely diagnosis and treatments for patients. The aim of
this article is to describe a needs assessment performed in a level-one academic
emergency department to establish the need for a dedicated team for patients with
difficult vascular access. Results from this assessment suggest that difficult
vascular access represents tangible threats to patient safety and increased use
of resources.
PMID- 28419012
TI - A Novel Needle-Free Blood Draw Device for Sample Collection From Short Peripheral
Catheters.
AB - A new US Food and Drug Administration-cleared needleless blood collection device
(PIVO; Velano Vascular, San Francisco, CA) for short peripheral catheters was
compared with conventional venipuncture for collecting blood samples for routine
laboratory analysis from adult healthy volunteers. The PIVO device was comparable
with venipuncture in terms of providing high-integrity samples (no hemolysis or
clotting), equivalent laboratory values, and better patient experience as
assessed by pain scores. Further studies to assess the overall utility of the
PIVO device are warranted.
PMID- 28419013
TI - Standardizing Best Nursing Practice for Implanted Ports: Applying Evidence-based
Professional Guidelines to Prevent Central Line-Associated Bloodstream
Infections.
AB - Nearly 3 million central vascular access devices (CVADs) are used in the United
States each year. These devices are an important advance in health care and
essential to oncology patients. However, CVADs are the most frequent cause of
central line-associated bloodstream infections (CLABSIs). CLABSI can be prevented
when evidence-based practices are followed consistently over time. Professional
organizations establish valid standards and guidelines to guide CVAD practice.
This article identifies strategies implemented at a comprehensive ambulatory
cancer center to integrate professional evidence-based standards and guidelines
for implanted port care into nursing practice at the point of care.
PMID- 28419014
TI - Impact of Ultrasound on Short Peripheral Intravenous Catheter Placement on Vein
Thrombosis Risk.
AB - Approximately 90% of hospitalized patients have a short peripheral intravenous
catheter (SPC) placed. Methods of inserting the catheter have evolved over time
and now include the use of ultrasound (US)-guided procedures for placement.
Little is known about the impact that US-guided procedures have on the vein. This
study compared the rate of venous thrombosis in patients with and without US
guided catheter placement. This prospective, single-blind, observational study
assessed for venous thrombosis in 153 veins from 135 patients. Veins were
evaluated by a research nurse blinded to the method of placement between 48 and
72 hours after the SPC was placed. The Fisher exact test showed a significant
difference between vessel compressibility and catheter insertion method (P =
.0012). The proportion of noncompressible veins was significantly greater when US
was used in comparison with freehand SPC insertion. The Mantel-Haenszel chi
square value of 10.34 (P = .0013) showed that US insertion technique is
associated with a higher likelihood of noncompressible veins. This pilot study
provides compelling evidence that the use of US to assist with catheter placement
is associated with a higher rate of noncompressible veins at day 2 or 3. Further
studies are needed with a larger sample to determine the generalizability of the
results from this pilot study.
PMID- 28419015
TI - An Unanticipated Complication of Atopic Dermatitis.
AB - An infant with a history of atopic dermatitis presented to the emergency
department on 5 occasions with flulike symptoms. Eventually, this child presented
with signs of infection and increased intracranial pressure: fever, bulging
anterior fontanel, and leukocytosis. A computed tomography scan identified a
large frontal lobe brain abscess. The abscess was surgically drained; culture was
positive for Staphylococcus aureus. The initial source of the infected brain
abscess was explored. Ultimately, it was thought to be secondary to impetiginized
atopic dermatitis, an unusual but serious consequence of a common skin condition.
PMID- 28419016
TI - An Evaluation of a New Debriefing Framework: REFLECT.
AB - BACKGROUND: Postresuscitation debriefing (PRD) is recommended by the American
Heart Association guidelines but is infrequently performed. Prior studies have
identified barriers for pediatric emergency medicine (PEM) fellows including lack
of a standardized curriculum. OBJECTIVE: Our objective was to create and assess
the feasibility of a time-limited, structured PRD framework entitled REFLECT:
Review the event, Encourage team participation, Focused feedback, Listen to each
other, Emphasize key points, Communicate clearly, and Transform the future.
METHODS: Each PEM fellow (n = 9) at a single center was a team leader of a pre
intervention and post-intervention videotaped, simulated resuscitation followed
by a facilitated team PRD. Our intervention was a 2-hour interactive, educational
workshop on debriefing and the use of the REFLECT debriefing aid. Videos of the
pre-intervention and post-intervention debriefings were blindly analyzed by video
reviewers to assess for the presence of debriefing characteristics contained in
the REFLECT debriefing aid. PEM fellow and team member assessments of the
debriefings were completed after each pre-intervention and post-intervention
simulation, and written evaluations by PEM fellows and team members were
analyzed. RESULTS: All 9 PEM fellows completed the study. There was an
improvement in the pre-intervention and post-intervention assessment of the
REFLECT debriefing characteristics as determined by fellow perception (63% to
83%, P < 0.01) and team member perception (63% to 82%, P < 0.001). All
debriefings lasted less than 5 minutes. There was no statistical difference
between pre-intervention and post-intervention debriefing time (P = 1.00).
CONCLUSIONS: REFLECT is a feasible debriefing aid designed to incorporate
evidence-based characteristics into a PRD.
PMID- 28419017
TI - The Evaluation of Trauma Care: The Comparison of 2 High-Level Pediatric Emergency
Departments in the United States and Turkey.
AB - OBJECTIVE: The purpose of the study is to compare the outcomes of pediatric
trauma patients with motor vehicle crashes (MVCs) and motor vehicle versus
pedestrian crashes (MPCs) at a level 1 pediatric trauma center in the United
States and a pediatric trauma center in Turkey. METHODS: The medical records of
all pediatric MVC and MPC subjects presenting to the emergency departments (EDs)
of a level 3 hospital in Turkey (Izmir Tepecik Training and Research Hospital
[ITTRH]) and a level 1 pediatric trauma center in the United States (Children's
Medical Center Dallas [CMCD]) over a 1-year period were reviewed. Data that were
collected include patient demographics, prehospital report (mechanism of injury,
mode of transportation), injury severity score (ISS), abbreviated injury scale
score, Glasgow Coma Scale score, ED length of stay, ED interventions, ED and
hospital disposition, and mortality. Patients with moderate (ISS, 5-15) and
severe (ISS, >15) trauma scores were included in the study. RESULTS: One hundred
six patient charts from the ITTRH and 125 patient charts from the CMCD with
moderate and severe ISS due to MVCs and MPCs were reviewed. Most of the patients
were pedestrians (86%) in the ITTRH group and passengers (60%) in the CMCD group.
The percentage of patients transferred by ambulance (ground or air) to the CMCD
and the ITTRH was 97.9% and 85%, respectively. Fifteen percent of ITTRH patients
and 2.1% of CMCD patients arrived by private vehicle. Emergency department
arrival ISS and Glasgow Coma Scale were similar between the 2 hospitals (P >
0.05). The overall mortality rate in the study population was 8.8% (11/125) at
the CMCD and 4.7% (5/106) at the ITTRH. (P = 0.223). Blood product utilization
was significantly higher in the CMCD group compared with the ITTRH group (P =
0.005). The use of hypertonic saline/mannitol/hyperventilation in patients with
significant head trauma and increased intracranial pressure was higher in the
ITTRH group (P = 0.000). CONCLUSIONS: This is the first study that compared
pediatric trauma care and outcome at a level 1 pediatric trauma center in the
United States and a pediatric hospital in Turkey. Our findings highlight the
opportunities to improve pediatric trauma care in Turkey. Specifically, there is
a need for national trauma registries, enhanced trauma education, and
standardized trauma patient care protocols. In addition, efforts should be
directed toward improving prehospital care through better integration within the
health care system and physician participation in educating prehospital
providers. Data and organized trauma care will be instrumental in system-wide
improvement and developing appropriate injury-prevention strategies.
PMID- 28419018
TI - Diagnosis of a Posterior Fracture Dislocation of the Medial Clavicle in an
Adolescent With Point-of-Care Ultrasound.
AB - We report a case of an adolescent patient with medial clavicular tenderness after
a fall on the lateral left shoulder. Initial radiographs did not reveal a
fracture or dislocation. Point-of-care ultrasound was used to diagnose a
posterior clavicular fracture dislocation.
PMID- 28419019
TI - Complexities of Consent: Ethics in the Pediatric Emergency Department.
AB - Informed consent is a communicative process of sharing information with patients,
which helps assure their understanding of the information provided and asks for
their permission to proceed. Informed consent allows a patient or a patient's
family to use his or her own value system to determine the need for a particular
procedure or test. Asking a patient for permission to treat requires the provider
to respect the patient's autonomy through allowing him or her to be an active
part of the decision-making process. Consent in the pediatric emergency
department can be a complex process. Parental consent is generally required for
medical evaluation and treatment of pediatric patients, but in the pediatric
emergency department, there are exceptions to this rule. If the provider
determines that a parent's refusal of consent places the child at risk of harm,
then consent is not necessary. By using the concepts of Emergency Medical
Treatment and Active Labor Act, in emergent situations, consent may not be
necessary. Finally, adolescents are often deeply concerned about privacy-their
acceptance of appropriate care is often based on this promise of confidentiality.
In the emergency department, adolescents can therefore be treated for issues
relating to reproductive care without parental consent. It is important for the
emergency department physician to understand the rules surrounding the care of
pediatric patients to avoid compromising their privacy and ultimately their well
being and medical care.
PMID- 28419020
TI - Education in the Waiting Room: Description of a Pediatric Emergency Department
Educational Initiative.
AB - OBJECTIVE: The aim of this study was to understand parents' awareness of and
reactions to a slide presentation based waiting-room educational initiative.
METHODS: This was a prospective observational study at a Canadian tertiary-care
pediatric emergency department (ED) with an annual census of 68,000 visits. An
anonymous parental survey was developed de novo, and parents were asked to
complete the survey during their low-acuity ED visit over a 2-week study period.
Descriptive statistics were used to describe responses and themes. RESULTS:
Parents completed 520 surveys (733 approached, 70.9% response rate). Eighty-three
percent of respondents had previously sought care in the ED. Most parents (68.9%)
were aware of the slide presentation, but only 33.7% were able to watch it in its
entirety (20 minutes' duration). Of those who watched the whole presentation,
62.9% understood that lower-acuity cases are assessed in the ambulatory zone of
the ED, and sicker children are assessed in the acute zone (89.4%), 79.9% felt
the presentation helped them to understand how the ambulatory zone functions, and
83.2% appreciated the current wait-time information. General questions about
common health concerns were answered correctly in 58.3% (fever), 56.0%
(gastroenteritis), 50.5% (abdominal pain/constipation), 35.7% (earache), and
17.0% (head injury). CONCLUSIONS: The majority of parents were aware of this
waiting-room educational initiative, but there was variable uptake of
information. Parents watching the entire presentation appreciated the information
provided, especially wait-time information, and felt it improved their
experience. Knowledge of common health conditions was low; novel methods of
knowledge transfer must be utilized and evaluated.
PMID- 28419021
TI - Clinical Toxicity of Acute Overdoses With L-Thyroxin in Children.
AB - OBJECTIVES: L-Thyroxine ingestion is rarely seen in children; here, we report our
experience of it. This study describes the clinical characteristics and
laboratory findings of acute L-thyroxine ingestion in children. METHODS: This
retrospective study enrolled patients treated for L-thyroxine ingestion at
Kayseri Teaching Hospital between September 2013 and September 2016. Clinical
characteristics and laboratory findings are described. Ethical approval was not
obtained because the study was retrospective. RESULTS: The incidence of L
thyroxine ingestion was 0.07% to 1.2% per year. There were 14 patients. Twelve
patients were asymptomatic, but 2 (14.2%) exhibited tachycardia and hypertension.
Thyroid hormone levels were elevated in 3 patients (21.4%). Eleven patients did
not require medical treatment (78.4%); 3 did. No serious complication or death
was observed. CONCLUSIONS: Acute ingestion has a benign course. Serious
complications are uncommon but may appear several hours or days after ingestion;
therefore, patients with L-thyroxine ingestion should be followed closely for 2
weeks.
PMID- 28419022
TI - Computed Tomography Angiographic Assessment of Acute Chest Pain.
AB - Acute chest pain is a leading cause of Emergency Department visits. Computed
tomography angiography plays a vital diagnostic role in such cases, but there are
several common challenges associated with the imaging of acute chest pain, which,
if unrecognized, can lead to an inconclusive or incorrect diagnosis. These
imaging challenges fall broadly into 3 categories: (1) image acquisition, (2)
image interpretation (including physiological and pathologic mimics), and (3)
result communication. The aims of this review are to describe and illustrate the
most common challenges in the imaging of acute chest pain and to provide
solutions that will facilitate accurate diagnosis of the causes of acute chest
pain in the emergency setting.
PMID- 28419023
TI - Interrelations of Epicardial Fat Volume, Left Ventricular T1-Relaxation Times and
Myocardial Strain in Hypertensive Patients: A Cardiac Magnetic Resonance Study.
AB - PURPOSE: This cardiac magnetic resonance study was performed to assess myocardial
fibrosis by evaluating T1-relaxation time (T1), to measure left ventricular (LV)
strain, and to determine epicardial fat volume (EFV) in hypertensive patients
with no history of cardiovascular (CV) events and to relate the results to the
presence of coronary atherosclerotic artery disease (CAD) in these patients.
MATERIALS AND METHODS: A total of 123 subjects were examined at 1.5 T. Of them,
98 were hypertensive patients (58 men; mean age, 62.9+/-10.7 y; body mass index,
29.0+/-5.6 kg/m) and 25 were controls without CV risk factors or disease (13 men;
60.1+/-10.7 y; 28.1+/-5.4 kg/m). All patients had a well-treated blood pressure.
In the hypertensive group, 56 patients had no CAD, whereas 42 patients had CAD.
T1 was assessed by a modified Look-Locker inversion recovery sequence.
Longitudinal and circumferential peak systolic strain (LS; CS) was determined
with dedicated cardiac magnetic resonance software (feature tracking). EFV
(normalized to the body surface area) was assessed by a 3D Dixon sequence.
RESULTS: T1 (ms) and EFV (mL/m) were higher and CS and LS (%) were lower in
hypertensive patients compared with those in nonhypertensive controls (P<0.05),
independent of the presence of CAD (controls: T1=967.2+/-16.9, LS=-25.2+/-4.6,
CS=-28.7+/-5.0, EFV=58.2+/-21.1; hypertensive patients overall: T1=991.3+/-45.5,
LS=-21.0+/-4.5, CS=-25.0+/-5.9, EFV=71.1+/-25.3; hypertensive patients without
CAD: T1=991.6+/-48.4, LS=-21.0+/-4.7, CS=-24.6+/-6.3, EFV=71.3+/-26.6;
hypertensive patients with CAD: T1=986.7+/-39.2, LS=-21.1+/-4.3, CS=-25.5+/-5.4,
EFV=70.9+/-23.6). There were no significant differences between hypertensive
patients with and those without CAD and between patients grouped according to the
number of vessels affected (0-vessel disease, 1-vessel disease, 2-vessel disease,
or 3-vessel disease). CONCLUSIONS: Hypertension is associated with signs of
myocardial fibrosis and an impaired LV contractility despite a normal LV ejection
fraction, as well as with an increased EFV. However, CAD, in the absence of
previous pathologies with consecutive myocardial ischemic damage, did not
additionally affect these parameters.
PMID- 28419024
TI - The Effects of Exercise Training on Anxiety in Fibromyalgia Patients: A Meta
analysis.
AB - : Physical inactivity and comorbid anxiety symptoms are prevalent among
fibromyalgia (FM) patients. Exercise training may be an effective alternative
therapy to reduce these symptoms. PURPOSE: This study aimed to evaluate the
effects of exercise training on anxiety symptoms in patients with FM and to
examine whether variables of theoretical or practical importance moderate the
estimated mean effect. METHODS: Twenty-five effects were derived from 10 articles
published before June 2016 located using Google Scholar, MEDLINE, PsycINFO,
PubMed, and Web of Science. Trials involved 595 patients with FM (mean age = 47.6
yr, 97.5% female) and included both randomization to exercise training (n = 297)
or a nonexercise control condition (n = 298) and an anxiety outcome measured at
baseline and during and/or after exercise training. Hedges' d effect sizes were
computed, data for moderator variables were extracted, and random effects models
were used to estimate sampling error and population variance for all analyses.
Meta-regression quantified the extent to which patient and trial characteristics
moderated the mean effect. RESULTS: Exercise training significantly reduced
anxiety symptoms by a mean effect Delta of 0.28 (95% confidence interval [CI] =
0.16-0.40). No significant heterogeneity was observed (Q24 = 30.79, P = 0.16, I =
25.29%). Program duration (beta = 1.44, z = 2.50, P <= 0.01) was significantly
related to the overall effect, with significantly larger anxiety improvements
resulting from programs lasting greater than 26 wk (Delta = 0.35, 95% CI = 0.05
0.66) compared with those lasting less than 26 wk (Delta = 0.26, 95% CI = 0.13
0.39). CONCLUSION: Exercise training improves anxiety symptoms among FM patients.
The findings also suggest that larger anxiety symptom reductions will be achieved
by focusing on longer exercise programs while promoting long-term adherence.
Future well-designed investigations are required to examine the potential
moderating effect of pain-related improvements in FM patients.
PMID- 28419025
TI - Ensemble Methods for Classification of Physical Activities from Wrist
Accelerometry.
AB - PURPOSE: To investigate whether the use of ensemble learning algorithms improve
physical activity recognition accuracy compared to the single classifier
algorithms, and to compare the classification accuracy achieved by three
conventional ensemble machine learning methods (bagging, boosting, random forest)
and a custom ensemble model comprising four algorithms commonly used for activity
recognition (binary decision tree, k nearest neighbor, support vector machine,
and neural network). METHODS: The study used three independent data sets that
included wrist-worn accelerometer data. For each data set, a four-step
classification framework consisting of data preprocessing, feature extraction,
normalization and feature selection, and classifier training and testing was
implemented. For the custom ensemble, decisions from the single classifiers were
aggregated using three decision fusion methods: weighted majority vote, naive
Bayes combination, and behavior knowledge space combination. Classifiers were
cross-validated using leave-one subject out cross-validation and compared on the
basis of average F1 scores. RESULTS: In all three data sets, ensemble learning
methods consistently outperformed the individual classifiers. Among the
conventional ensemble methods, random forest models provided consistently high
activity recognition; however, the custom ensemble model using weighted majority
voting demonstrated the highest classification accuracy in two of the three data
sets. CONCLUSIONS: Combining multiple individual classifiers using conventional
or custom ensemble learning methods can improve activity recognition accuracy
from wrist-worn accelerometer data.
PMID- 28419026
TI - The Gas Sampling Interval Effect on VO2peak Is Independent of Exercise Protocol.
AB - INTRODUCTION: There is a plethora of gas sampling intervals available during
cardiopulmonary exercise testing to measure peak oxygen consumption (VO2peak).
Different intervals can lead to altered VO2peak. Whether differences are affected
by the exercise protocol or subject sample is not clear. The purpose of this
investigation was to determine whether VO2peak differed because of the
manipulation of sampling intervals and whether differences were independent of
the protocol and subject sample. METHODS: The first subject sample (24 +/- 3 yr;
VO2peak via 15-breath moving averages: 56.2 +/- 6.8 mL.kg.min) completed the
Bruce and the self-paced VO2max protocols. The second subject sample (21.9 +/-
2.7 yr; VO2peak via 15-breath moving averages: 54.2 +/- 8.0 mL.kg.min) completed
the Bruce and the modified Astrand protocols. VO2peak was identified using five
sampling intervals: 15-s block averages, 30-s block averages, 15-breath block
averages, 15-breath moving averages, and 30-s block averages aligned to the end
of exercise. Differences in VO2peak between intervals were determined using
repeated-measures ANOVAs. The influence of subject sample on the sampling effect
was determined using independent t-tests. RESULTS: There was a significant main
effect of sampling interval on VO2peak (first sample Bruce and self-paced VO2max
P < 0.001; second sample Bruce and modified Astrand P < 0.05). The difference in
VO2peak between sampling intervals followed a similar pattern for each protocol
and subject sample, with 15-breath moving average presenting the highest VO2peak.
CONCLUSIONS: The effect of manipulating gas sampling intervals on VO2peak appears
to be protocol and sample independent. These findings highlight our
recommendation that the clinical and scientific community request and report the
sampling interval whenever metabolic data are presented. The standardization of
reporting would assist in the comparison of VO2peak.
PMID- 28419027
TI - Athletes Intending to Use Sports Supplements Are More Likely to Respond to a
Placebo.
AB - PURPOSE: We investigated associations between athletes' use of sport supplements
and their responsiveness to placebo and nocebo interventions. METHODS:
Participants (n = 627) reported their intention to use, and actual use of, sport
supplements. They then completed a 5 * 20 m repeat sprint protocol in the
baseline condition, before being randomized to one of three treatments.
Participants in the positive-belief treatment were administered an inert capsule
described as a potent supplement which would improve sprint performance.
Participants in the negative-belief treatment were administered an inert capsule
described as a potent supplement which would negatively affect sprint
performance. Participants in the control treatment received neither instruction
nor capsule. Twenty minutes after baseline trials, all participants completed the
same repeat sprint protocol in the experimental condition. RESULTS: Compared with
controls, no mean differences in performance were observed between baseline and
experimental conditions for the positive-belief treatment (-0.07% +/- 0.27%, d =
0.02), but mean differences were observed for the negative-belief treatment (
0.92% +/- 0.31%, d = 0.32), suggesting a moderate nocebo effect. In the positive
belief treatment, however, a relationship between intention to use supplements
and performance was observed. Performance worsened by -1.10% +/- 0.30% compared
with baseline for participants not intending to use supplements, worsened by
0.64% +/- 0.43% among those undecided about supplement use, but improved by 0.19%
+/- 0.24% among those participants intending to use supplements. CONCLUSIONS:
Information about a harmful supplement worsened repeat sprint performance (a mean
nocebo effect), whereas information about a beneficial supplement did not improve
performance (no mean placebo effect was observed). However, participants'
intention to use sport supplements influenced the direction and magnitude of
subsequent placebo responses, with participants intending to use supplements more
likely to respond to the positive intervention.
PMID- 28419028
TI - Physical Activity Assessment with the ActiGraph GT3X and Doubly Labeled Water.
AB - PURPOSE: To compare the degree to which four accelerometer metrics-total activity
counts per day (TAC per day), steps per day (steps per day), physical activity
energy expenditure (PAEE) (kcal.kg.d), and moderate- to vigorous-intensity
physical activity (MVPA) (min.d)-were correlated with PAEE measured by doubly
labeled water (DLW). Additionally, accelerometer metrics based on vertical axis
counts and triaxial counts were compared. METHODS: This analysis included 684
women and 611 men age 43 to 83 yr. Participants wore the Actigraph GT3X on the
hip for 7 d twice during the study and the average of the two measurements was
used. Each participant also completed one DLW measurement, with a subset having a
repeat. PAEE was estimated by subtracting resting metabolic rate and the thermic
effect of food from total daily energy expenditure estimated by DLW. Partial
Spearman correlations were used to estimate associations between PAEE and each
accelerometer metric. RESULTS: Correlations between the accelerometer metrics and
DLW-determined PAEE were higher for triaxial counts than vertical axis counts.
After adjusting for weight, age, accelerometer wear time, and fat free mass, the
correlation between TAC per day based on triaxial counts and DLW-determined PAEE
was 0.44 in women and 0.41 in men. Correlations for steps per day and
accelerometer-estimated PAEE with DLW-determined PAEE were similar. After
adjustment for within-person variation in DLW-determined PAEE, the correlations
for TAC per day increased to 0.61 and 0.49, respectively. Correlations between
MVPA and DLW-determined PAEE were lower, particularly for modified bouts of >=10
min. CONCLUSIONS: Accelerometer measures that represent total activity volume,
including TAC per day, steps per day, and PAEE, were more highly correlated with
DLW-determined PAEE than MVPA using traditional thresholds and should be
considered by researchers seeking to reduce accelerometer data to a single
metric.
PMID- 28419029
TI - Females with Unexplained Joint Pain Following Total Joint Arthroplasty Exhibit a
Higher Rate and Severity of Hypersensitivity to Implant Metals Compared with
Males: Implications of Sex-Based Bioreactivity Differences.
AB - BACKGROUND: Recent studies indicate that females demonstrate an increased risk of
experiencing adverse local tissue reactions, aseptic loosening, and revision
after primary metal-on-metal hip resurfacing arthroplasty compared with males;
the underlying biological mechanisms responsible for sex discrepancies in implant
failure remain unclear. In addition to anatomical and biomechanical sex
differences, there may be inherent immunological disparities that predispose
females to more aggressive adaptive immune reactivity to implant debris, i.e.,
metal sensitivity. METHODS: In this retrospective study, we analyzed sex
associated rates and levels of metal sensitization in 1,038 male and 1,575 female
subjects with idiopathic joint pain following total joint arthroplasty (TJA) who
were referred for in vitro metal-sensitivity testing. RESULTS: Females
demonstrated a significantly higher rate and severity of metal sensitization
compared with males. The median lymphocyte stimulation index (SI) among males was
2.8 (mean, 5.4; 95% confidence interval [CI], 4.9 to 6.0) compared with 3.5
(mean, 8.2; 95% CI, 7.4 to 9.0) among females (p < 0.05). Forty-nine percent of
females had an SI of >=4 (reactive) compared with 38% of males, and the implant
related level of pain was also significantly (p < 0.0001) higher among females
(mean, 6.8; 95% CI, 6.6 to 6.9) compared with males (mean, 6.1; 95% CI, 6.0 to
6.3). CONCLUSIONS: In a select group of patients who had joint pain following TJA
and no evidence of infection and who were referred for metal-sensitivity testing,
females exhibited a higher level of pain and demonstrated a higher rate and
severity (as measured by lymphocyte SI) of metal sensitization compared with
males. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for
a complete description of levels of evidence.
PMID- 28419030
TI - Ambulatory Total Shoulder Arthroplasty: A Comprehensive Analysis of Current
Trends, Complications, Readmissions, and Costs.
AB - BACKGROUND: There have been few studies that have evaluated ambulatory total
shoulder arthroplasty. The objectives of the present study were to investigate
the current trends in ambulatory total shoulder arthroplasty in the United
States; to characterize the rate of postoperative complications, hospital
readmission, and risk factors associated with readmission; and to conduct a cost
analysis comparing ambulatory total shoulder arthroplasty with matched inpatient
total shoulder arthroplasty. METHODS: A national insurance database was queried
for patients who underwent anatomic total shoulder arthroplasty between the
fourth quarter of 2010 and 2014. Patients undergoing ambulatory total shoulder
arthroplasty and a matched group of patients undergoing inpatient total shoulder
arthroplasty were identified. Complications were assessed for both groups. Risk
factors for readmission within 90 days postoperatively were examined. The costs
up to 30 days postoperatively were evaluated for patients who underwent
ambulatory total shoulder arthroplasty and controls. RESULTS: Included in the
study were 706 patients who underwent ambulatory total shoulder arthroplasty.
From the fourth quarter of 2010 to 2014, the yearly incidence of ambulatory total
shoulder arthroplasty doubled. In the study, 4,459 patients who underwent
inpatient total shoulder arthroplasty were matched to patients who underwent
ambulatory total shoulder arthroplasty. In no instances were any complications
present at a significantly higher rate in the patients who underwent ambulatory
total shoulder arthroplasty. The rate of readmission was not significantly
different (p > 0.05) between the 2 cohorts. The patients undergoing ambulatory
total shoulder arthroplasty had significantly lower costs (p < 0.0001) at $14,722
compared with the matched controls at $18,336 in numerous itemized cost
categories as well as costs related to diagnosis-related groups. CONCLUSIONS: In
appropriately selected patients, ambulatory total shoulder arthroplasty is a
viable and safe practice model. Ambulatory total shoulder arthroplasty also
offers significant cost savings compared with inpatient total shoulder
arthroplasty in matched patients. LEVEL OF EVIDENCE: Therapeutic Level III. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 28419031
TI - Prognostic Factors Affecting Union After Ulnar Shortening Osteotomy in Ulnar
Impaction Syndrome: A Retrospective Case-Control Study.
AB - BACKGROUND: Ulnar shortening osteotomy (USO) is a widely adopted procedure with
excellent outcomes. However, delayed union or nonunion has occasionally been
observed. The purpose of this retrospective case-control study was to identify
variables affecting osseous consolidation after USO in patients with ulnar
impaction syndrome. METHODS: The study included 325 patients who had undergone
USO between March 2008 and March 2014. We evaluated the association between union
and basic demographic factors as well as preoperative pain (assessed on a visual
analog scale [VAS]), range of wrist motion, grip strength, and modified Mayo
wrist score. We also assessed the association of union with radiographic
variables such as the degree of dorsal subluxation of the ulna, preoperative and
postoperative ulnar variance, morphological type of the distal radioulnar joint,
gap at the osteotomy site, and presence of newly developed arthritic changes
during the follow-up period. Finally, variables associated with operative
conditions, such as degeneration of the triangular fibrocartilage complex, use of
a parallel double-blade saw, type of plate used for fixation, number of screws,
and plate position on the volar or dorsal ulnar surface were investigated.
RESULTS: Ulnar union was achieved in 294 patients (group 1), and 31 patients had
delayed union or nonunion (group 2). On univariate and multivariate analyses,
smoking, low bone mineral density (BMD), a decreased range of motion of the
wrist, and use of a double-blade saw were found to be significant factors for an
adverse radiographic outcome (nonunion or delayed union). CONCLUSIONS: Delayed
union or nonunion occurred in about 10% of patients treated with USO. We suggest
that it may be preferable to perform USO in nonsmokers, patients with normal bone
density, and those without restricted wrist motion. Also, we recommend the use of
a single-blade saw when performing the osteotomy. LEVEL OF EVIDENCE: Therapeutic
Level III. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 28419032
TI - Formal Physical Therapy After Total Hip Arthroplasty Is Not Required: A
Randomized Controlled Trial.
AB - BACKGROUND: The value of formal physical therapy after total hip arthroplasty is
unknown. With substantial changes that have occurred in surgical and anesthesia
techniques, self-directed therapy may be efficacious in restoring function to
patients undergoing total hip arthroplasty. METHODS: We conducted a single
center, randomized trial of 120 patients undergoing primary, unilateral total hip
arthroplasty who were eligible for direct home discharge. The experimental group
followed a self-directed home exercise program for 10 weeks. The control group
received the standard protocol for physical therapy that included in-home visits
with a physical therapist for the first 2 weeks followed by formal outpatient
physical therapy for 8 weeks. Functional outcomes were measured using validated
instruments including the Harris hip score (HHS), the Western Ontario and
McMaster Universities Osteoarthritis Index (WOMAC), and the Short Form-36 Health
Survey (SF-36) preoperatively, at 1 month postoperatively, and at 6 to 12 months
postoperatively. RESULTS: Of 120 randomized patients, 108 were included in the
final analysis. Ten patients (19%) were randomized to unsupervised home exercise
and 20 patients (37%) were randomized to formal outpatient therapy crossed over
between groups. There was no significant difference in any of the measured
functional outcomes between patients receiving formal therapy (n = 54) and those
participating in unsupervised home exercise (n = 54) at any time point (HHS, p =
0.82; WOMAC, p = 0.80; and SF-36 physical health, p = 0.90). CONCLUSIONS: This
randomized trial suggests that unsupervised home exercise is both safe and
efficacious for a majority of patients undergoing total hip arthroplasty, and
formal physical therapy may not be required. LEVEL OF EVIDENCE: Therapeutic Level
I. See Instructions for Authors for a complete description of levels of evidence.
PMID- 28419034
TI - Complications and Functional Outcomes After Pantalar Dislocation.
AB - BACKGROUND: Pantalar dislocations without associated talar fracture are rare and
have high risks of complications, including infection, osteonecrosis, and
posttraumatic osteoarthrosis. Limited information on later function exists. This
study evaluated complications and outcomes following pantalar dislocation without
talar fracture. METHODS: Nineteen patients were identified with open (n = 14) or
closed (n = 5) pantalar dislocations without talar fracture. Ten male and 9
female patients with a mean age of 39.6 years (range, 19 to 68 years) were
included. Open injuries underwent surgical debridement. Sixteen patients had open
reduction, and 2 had closed reduction. Fixation was achieved with Kirschner wires
(n = 4), external fixation (n = 9), or both (n = 3). Two patients did not have
fixation. Another patient had primary transtibial amputation due to
nonreconstructible foot trauma. Charts and radiographs were reviewed to identify
infection, osteonecrosis, and posttraumatic arthrosis. Data on pain, medications,
range of motion, and secondary procedures were collected. After a minimum of 1
year, Foot Function Index (FFI) and Musculoskeletal Function Assessment (MFA)
surveys were administered. RESULTS: The mean clinical follow-up was 45.1 months.
Two patients had superficial wound-healing problems with prolonged drainage,
which healed with dressing changes and oral antibiotics, and 1 patient developed
cellulitis 4 months after injury, which resolved with intravenous antibiotics. No
deep wound infections occurred. Fourteen (88%) of the 16 patients with a minimum
of 11 months of radiographic follow-up developed osteonecrosis, 2 with collapse
of the talar dome, and 7 (44%) developed arthrosis of >=1 peritalar articulation.
Outcome surveys were obtained for 11 (58%) of the 19 patients, at a mean of 5.2
years after injury. The mean MFA score was 30.3, and the mean FFI score was 25.3.
Six of 10 survey respondents had returned to employment, but 88% (14 of 16) of
the patients with radiographic and clinical follow-up reported at least mild pain
and 75% (12 of 16) were taking analgesics. CONCLUSIONS: Urgent surgical
debridement of open injuries and reimplantation of the talus after pantalar
dislocation was not associated with deep infection. Osteonecrosis occurred in the
majority of patients, but collapse was uncommon. Persistent pain and functional
limitations are frequent after pantalar dislocation, as reflected in extremity
specific and generalized functional outcome scores. LEVEL OF EVIDENCE:
Therapeutic Level IV. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 28419035
TI - Clinical Practice Guidelines Decrease Unnecessary Echocardiograms Before Hip
Fracture Surgery.
AB - BACKGROUND: Preoperative assessment of geriatric patients with a hip fracture may
include transthoracic echocardiography (TTE), which increases resource
utilization and cost and may delay surgery. The purpose of this study was to
evaluate preoperative TTE utilization at a single institution in order to
determine (1) how often TTE is ordered in accordance with clinical practice
guidelines (CPGs), (2) how frequently TTE reveals cardiac disease that may alter
medical or anesthesia management, and (3) whether following CPGs reduces
unnecessary TTE utilization without potentially missing important disease.
METHODS: A retrospective review of data on 100 geriatric patients with a hip
fracture who had undergone preoperative TTE was performed. Charts were reviewed
to evaluate if TTE had been obtained in accordance with the published CPGs from
the American College of Cardiology/American Heart Association (ACC/AHA). TTE
reports were reviewed for the presence of disease that was important enough to
cause modifications in anesthesia or perioperative management, including new left
ventricular systolic or diastolic dysfunction, moderate or severe valvular
disease, and pulmonary hypertension. Finally, the sensitivity and specificity of
accordance with the ACC/AHA CPGs for predicting which patients would have TTE
that identified important disease were calculated. RESULTS: The TTE was ordered
in accordance with the published ACC/AHA CPGs for 66% of the patients. TTE
revealed disease with the potential to modify anesthesia or medical management in
14% of the patients-for all of whom the TTE had been indicated according to
ACC/AHA guidelines (i.e., the guidelines were 100% sensitive). In this study
population, following the ACC/AHA guidelines could have prevented the performance
of TTE in 34% of the patients without missing any disease (40% specificity).
CONCLUSIONS: Preoperative TTE for patients with a hip fracture is frequently
obtained outside the recommendations of established CPGs. Utilization of CPGs
such as the ACC/AHA guidelines should be considered, as it may decrease
variability in care and reduce unnecessary resource utilization without adversely
affecting patient outcomes.
PMID- 28419033
TI - Oral-Only Linezolid-Rifampin Is Highly Effective Compared with Other Antibiotics
for Periprosthetic Joint Infection: Study of a Mouse Model.
AB - BACKGROUND: The medical treatment of periprosthetic joint infection (PJI)
involves prolonged systemic antibiotic courses, often with suboptimal clinical
outcomes including increased morbidity and health-care costs. Oral and
intravenous monotherapies and combination antibiotic regimens were evaluated in a
mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI. METHODS:
Oral linezolid with or without oral rifampin, intravenous vancomycin with oral
rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin,
oral doxycycline, or sham treatment were administered at human-exposure doses for
6 weeks in a mouse model of PJI. Bacterial burden was assessed by in vivo
bioluminescent imaging and ex vivo counting of colony-forming units (CFUs), and
reactive bone changes were evaluated with radiographs and micro-computed
tomography (MUCT) imaging. RESULTS: Oral-only linezolid-rifampin and all
intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria
and minimized reactive bone changes. Although oral linezolid was the most
effective monotherapy, all oral and intravenous antibiotic monotherapies failed
to clear infection or prevent reactive bone changes. CONCLUSIONS: Combination
antibiotic-rifampin regimens, including oral-only linezolid-rifampin and the
newer ceftaroline-rifampin combinations, were highly effective and more
efficacious than monotherapies when used against a preclinical MRSA PJI. CLINICAL
RELEVANCE: This study provides important preclinical evidence to better optimize
future antibiotic therapy against PJIs. In particular, the oral-only linezolid
rifampin option might reduce venous access complications and health-care costs.
PMID- 28419036
TI - Emerging U.S. National Trends in the Treatment of Pediatric Supracondylar Humeral
Fractures.
AB - BACKGROUND: Understanding national trends in the treatment of pediatric
supracondylar humeral fractures will provide important insight into variations in
regional treatment and identify areas for improving value and quality in care
delivery in the U.S. METHODS: U.S. national trends in the treatment of
supracondylar humeral fractures were evaluated through query of the Humana (2007
to 2014) and ING (2007 to 2011) administrative claims databases. Geographic
variation and changes in surgical and transfer rates over time were further
explored through the Nationwide Emergency Department Sample (NEDS) database (2006
to 2011). Hospital characteristics impacting treatment decisions were identified.
RESULTS: A total of 29,642 pediatric patients with supracondylar humeral
fractures were identified in the administrative claims databases and a projected
63,348 encounters for supracondylar humeral fracture were identified in the NEDS
database. The majority of the patients (76.1%; 22,563 of 29,642) were treated
definitively with cast immobilization. Operative treatment was performed in 23.9%
of the patients (7,079 of 29,642), with no change observed in the operative rate
over time (p = 0.055). Of patients undergoing operative treatment, closed
reduction and percutaneous pinning (CRPP) was performed in 87.3%, with a
significant increase noted in the rate of CRPP over time (p = 0.0001); open
reduction was performed in 12.7%, with a significant decrease noted in the rate
of open reduction over time (p < 0.0001). Regional surgical rates generally
showed significant variation from 2006 to 2010, followed by a convergence in the
surgical rate among all geographic regions in 2011. These trends occurred
simultaneous to a significant increase in transfer rates nationwide, from 5.6% in
2006 to 9.1% in 2011 (p = 0.0011). Transfer rates were significantly higher (p <
0.0001) for nontrauma, nonteaching, and nonmetropolitan centers while surgical
rates were significantly higher (p < 0.0001) for trauma, teaching, and
metropolitan centers when rates were analyzed by hospital designation.
CONCLUSIONS: Operative treatment was performed in 24% of pediatric patients with
supracondylar humeral fractures from 2007 to 2014. There was a convergence of
surgical rates across geographic regions, suggesting that a "standard of care" in
the treatment of supracondylar humeral fractures is being established nationally.
CLINICAL RELEVANCE: Cases of pediatric supracondylar humeral fracture are
increasingly being transferred to and, when managed surgically, receiving care at
metropolitan facilities designated as trauma centers or teaching hospitals, with
a corresponding decrease observed in the rate of open reduction. The optimization
of nationwide referral and treatment patterns may improve value in care delivery.
PMID- 28419037
TI - Depression and Patient-Reported Outcomes Following Total Shoulder Arthroplasty.
AB - BACKGROUND: Recent studies have found that depression is associated with
increased pain and impairment following lower-extremity arthroplasty; however,
this association has not been investigated for total shoulder arthroplasty. The
objective of this study was to investigate the association between depression and
patient-reported outcomes following total shoulder arthroplasty. METHODS: A
prospectively collected institutional registry was queried for consecutive
patients who underwent total shoulder arthroplasty for osteoarthritis from 2007
to 2013 with baseline and minimum 2-year postoperative American Shoulder and
Elbow Surgeons (ASES) scores. Revision procedures and total shoulder arthroplasty
for diagnoses other than osteoarthritis were excluded. Patients with a
preoperative diagnosis of depression (n = 88) formed the study cohort; control
patients without a diagnosis of depression were matched to the study patients by
age and sex in a 2:1 ratio (n = 176). Baseline characteristics and patient
reported outcome measures were compared between groups, as were minimum 2-year
patient-reported outcomes and change in patient-reported outcomes. A
multivariable regression was performed to investigate the independent effect of
depression on improvement in ASES scores. RESULTS: Except for the Short Form-12
Mental Component Summary (SF-12 MCS) scores, there were no significant
differences (p > 0.05) in baseline characteristics between study patients and
controls. There was a significant improvement in the ASES score for patients with
depression (p < 0.0001) and controls (p < 0.0001). Patients with depression had
significantly lower final ASES scores (p = 0.001) and less improvement in ASES
scores (p = 0.001) and SF-12 Physical Component Summary scores (p = 0.006) as
well as lower satisfaction levels at 2 years; however, the latter difference did
not reach clinical importance. Depression (p = 0.018) was an independent
predictor of less improvement in ASES scores. CONCLUSIONS: Patients with a
diagnosis of depression should be counseled that they will experience a
significant clinical improvement from baseline after total shoulder arthroplasty.
A preoperative diagnosis of depression is an independent predictor of
significantly less improvement in ASES scores following total shoulder
arthroplasty; however, this difference does not reach clinical importance and
should not discourage patients with a clinical diagnosis of depression from
undergoing total shoulder arthroplasty. LEVEL OF EVIDENCE: Prognostic Level III.
See Instructions for Authors for a complete description of levels of evidence.
PMID- 28419038
TI - The American Academy of Orthopaedic Surgeons Appropriate Use Criteria for
Surgical Management of Osteoarthritis of the Knee.
PMID- 28419039
TI - What's New in Foot and Ankle Surgery.
PMID- 28419040
TI - Measurement of Distal Ulnar Hounsfield Units Accurately Predicts Bone Mineral
Density of the Forearm.
AB - BACKGROUND: Hounsfield unit (HU) measurement obtained from computed tomography
(CT) scans of the wrist is a potential new screening method for low bone mineral
density (BMD). We hypothesized that HU measurements of the ulnar head obtained
from CT scans would correlate with BMD assessed with dual x-ray absorptiometry
(DXA) scans of the forearm. METHODS: Patients with both upper-extremity CT and
DXA scans performed at a single institution were included in the study.
Hounsfield units were manually measured in the distal part of the ulna by 1
author blinded to the DXA results. Average values were then compared with forearm
BMD values as determined with a DXA scan. RESULTS: Seventy-seven CT scans of 74
patients were included. Average HU values were significantly lower in the
osteoporotic and osteopenic groups in comparison with the normal BMD group. The
upper limit of the 95% confidence interval for osteopenic patients was 145.9 HU.
The average forearm T-score for patients with an HU value at or below the cutoff
of 146 was significantly lower than the average T-score for those with an HU
value of >146 HU (p < 0.0001). Sensitivity and negative predictive value for low
BMD using this cutoff value were calculated to be 91% and 89%, respectively.
CONCLUSIONS: Distal ulnar HU measurements accurately reflect the BMD of the
forearm as diagnosed with a DXA scan. Our results suggest that distal ulnar HU
measurements of <=146 HU are strongly associated with low BMD and that values
above this cutoff accurately rule out low forearm BMD with a high degree of
sensitivity and negative predictive value. Utilizing this technique may improve
the capture of at-risk patients and streamline the screening process for
osteoporosis. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for
Authors for a complete description of levels of evidence.
PMID- 28419041
TI - Accuracy of Computer-Aided Techniques in Orthopaedic Surgery: How Can It Be
Defined, Measured Experimentally, and Analyzed from a Clinical Perspective?
AB - Surgical accuracy is multifactorial. Therefore, it is crucial to consider all
influencing factors when investigating the accuracy of a surgical procedure, such
as the surgeon's experience, the assistive technologies that may be used by the
surgeon, and the patient factors associated with the specific anatomical site.
For in vitro preclinical investigations, accuracy should be linked to the
concepts of trueness (e.g., distance from the surgical target) and precision
(e.g., variability in relation to the surgical target) to gather preclinical,
quantitative, objective data on the accuracy of completed surgical procedures
that have been performed with assistive technologies. The clinical relevance of
improvements in accuracy that have been observed experimentally may be evaluated
by analyzing the impact on the risk of failure and by taking into account the
level of tolerance in relation to the surgical target (e.g., the extent of the
safety zone). The International Organization for Standardization (ISO)
methodology enables preclinical testing of new assistive technologies to quantify
improvements in accuracy and assess the benefits in terms of reducing the risk of
failure and achieving surgical targets with tighter tolerances before the testing
of clinical outcomes.
PMID- 28419042
TI - Geriatric Fracture Care: Future Trajectories: A 2015 AOA Critical Issues
Symposium.
AB - The population of the United States and the world is aging rapidly.
Musculoskeletal care for older adults will be impacted by the manner in which
health care is financed and the ability of the orthopaedic community to provide
evidence-based integrated care for this population. We review the financial
aspects of health-care reform and the implications for musculoskeletal care in
the elderly. We discuss the establishment of quality measures for hip fracture
care in the elderly, team building to accomplish this, and an innovative program
designed to provide orthopaedic care to the frail elderly outside of the usual
office setting.
PMID- 28419043
TI - Confirmation of Sexual Dimorphisms in Metal Hypersensitivity and Joint Pain
Following Total Joint Arthroplasty: Commentary on an article by Marco S. Caicedo,
PhD, et al.: "Females with Unexplained Joint Pain Following Total Joint
Arthroplasty Exhibit a Higher Rate and Severity of Hypersensitivity to Implant
Metals Compared with Males. Implications of Sex-Based Bioreactivity Differences".
PMID- 28419044
TI - Resiliency Is Good for You: Commentary on an article by Brian C. Werner, MD, et
al.: "Depression and Patient-Reported Outcomes Following Total Shoulder
Arthroplasty".
PMID- 28419045
TI - Ultrasound Guidance for Trigger Point Injections: Gold Standard or Fool's Gold?
PMID- 28419046
TI - Point-of-Care Ultrasound for the Regional Anesthesiologist and Pain Specialist: A
Series Introduction.
PMID- 28419047
TI - The Subsartorial Approach to the Continuous Adductor Canal Block: Safer?
PMID- 28419048
TI - Reply to Dr Kelly et al.
PMID- 28419049
TI - An Anatomical Basis for Naming Plane Blocks of the Anteromedial Chest Wall.
PMID- 28419050
TI - Periosteal Infusion of Local Anesthetics as an Alternative to Bilateral
Subpectoral Interfascial Plane Catheters in Patients With Sternal Fractures.
PMID- 28419051
TI - Reply to Dr Eid et al.
PMID- 28419052
TI - It's Not Just About the Diaphragm.
PMID- 28419053
TI - Reply to Dr Price.
PMID- 28419054
TI - Local Anesthetic Diffusion of Bilateral Sternal Block After Cardiac Surgery.
PMID- 28419055
TI - Be the Change: An Interprofessional Team-Based Health Advocacy Summit.
AB - In a complex health care environment, nursing and health care professional
graduates should be able to understand and collaboratively advocate for health
policy benefitting patients, families, and communities. This study explored the
effectiveness of interprofessional team-based learning to improve political
astuteness in undergraduate health profession students. This engaging method may
prove to enhance health care professionals' likelihood of understanding,
involvement, and influencing health policy in the future.
PMID- 28419056
TI - Response characteristics of the rat anterior cingulate cortex to ultrasonic
communicative vocalizations.
AB - Emotional communication involves transmitting information on affective states.
Rat 50- and 22-kHz ultrasonic vocalizations (USVs) are emotional communication
signals that reflect positive or negative states, respectively. In general,
emotional communication signals that elicit changes in event-related potentials
(ERPs), suggesting a specific mechanism for processing these signals. As this is
observed in several communication systems including humans, we hypothesized that
rat USVs can also trigger such changes. In this study, we measured rat local
field potentials and used them to calculate ERPs from the anterior cingulate
cortex (ACC), an area related to motor production of USVs. In Experiment 1, we
measured ERPs to pure tones with peak frequencies around 50 or 22 kHz to examine
whether the ACC is involved in auditory sensory processing related to pitch. The
results showed that pure tones around 50 kHz elicited large amplitude ERPs,
whereas those around 22 kHz resulted in smaller ERPs. In Experiment 2, we
compared ERPs in response to rat USVs (emotional stimuli) with ERPs to pure tones
modeled after USVs (neutral stimuli). The peak frequencies were the same between
USVs and neutral sounds, but USVs showed more frequency modulation than neutral
sounds. USVs elicited larger changes in the amplitude of ERP components than
neutral stimuli did. These experiments suggest that the rat ACC is sensitive to
frequencies around 50 and 22 kHz, and is especially tuned to frequency modulation
around these frequencies. Taken together, the rat ACC may process the emotional
content of communication signals on the basis of pitch and frequency modulation.
PMID- 28419057
TI - GABAergic modulation of noradrenaline release caused by blood pressure changes in
the rat median preoptic area.
AB - Experiments using in-vivo microdialysis methods were conducted to investigate
whether blood pressure changes cause an alteration in the release of
noradrenaline (NA) in the median preoptic nucleus (MnPO) and whether the gamma
aminobutyric acid (GABA) receptor mechanism is involved in the modulation of the
pressure response-induced alteration in the NA release. In urethane-anesthetized
male rats, intravenous administration of metaraminol, an alpha-agonist,
significantly produced an increase in dialysate NA concentration in the MnPO area
accompanied by an elevation in the mean arterial pressure (MAP). Perfusion with
GABA (10 MUM) through the dialysis probe elicited a significant decrease in
either MAP or the NA concentration in the MnPO area. Similar perfusion with
either the GABAA receptor antagonist bicuculline (10 MUM) or the GABAB receptor
antagonist phaclofen (10 MUM) caused a significant increase in both MAP and the
NA release in the MnPO area. Either bicuculline or phaclofen administered
together with the metaraminol further enhanced the metaraminol-induced MAP and NA
release in the MnPO area. The degree of increases in the both MAP of the NA
release was significantly greater in the bicuculline-treated group than in the
phaclofen-treated group. These results suggest that the NA release in the MnPO
area may be potentiated during an elevation in arterial pressure caused by the
metaraminol injection and imply that the NA release may be mediated through GABAA
receptors rather than GABAB receptors in the MnPO area.
PMID- 28419058
TI - A method for u-fiber quantification from 7 T diffusion-weighted MRI data tested
in patients with nonlesional focal epilepsy.
AB - In this methods development, we present an ultra-high-field, diffusion-weighted
MRI method to quantitatively assess u-fibers and use it to compare u-fiber counts
in nonlesional epilepsy patients with controls. Emerging evidence implicates
white matter abnormalities in nonlesional epilepsy, including the short-range,
cortical-cortical connections, or u-fibers. Eight patients with nonlesional
epilepsy and eight demographically matched controls underwent 7 T MRI consisting
of a T1-weighted sequence (0.7 mm isotropic resolution) and high-angular-resolved
diffusion-weighted MRI (1.05 mm isotropic resolution, 68 directions). MRI data
were used to quantify u-fiber counts in known u-fiber populations on the basis of
an atlas and fiber tractography. From tractography, connectivity matrices
summarizing the u-fiber counts were computed. Quantitative group comparisons were
performed on the connectivity matrices. U-fiber counts were found to be lower on
average in patients with epilepsy than in healthy controls. The results indicate
that the density or the number of u-fibers is reduced in patients with
nonlesional epilepsy. Future work will focus on histological validation and
determining whether differences in u-fiber counts can be used clinically to
noninvasively identify seizure-onset zones.
PMID- 28419059
TI - Late-onset nivolumab-mediated pneumonitis in a patient with melanoma and multiple
immune-related adverse events.
AB - Immune-related adverse effects (AEs) of PD-1 inhibitors can affect almost every
organ, but the skin, intestine, lung, eye, and liver are the most commonly
affected organs. Here, we present the case of a 62-year-old female patient with
stage IIIc melanoma treated with nivolumab in an adjuvant setting who
sequentially developed hyperthyroidism, hypothyroidism, acute hepatitis, and
pneumonitis. Six months before the emergence of pneumonitis, the patient had
discontinued treatment with nivolumab because of acute hepatitis. Information on
pneumonitis after nivolumab discontinuation in the literature is scarce, whereas
most of the cases emerge during the first 2.5 months of treatment. Patients with
multiple immune-related AEs comprise a group of special interest as the
identification of factors affecting the susceptibility of patients to immune
related AEs of PD-1 inhibitors may lead to a more rational use of these drugs.
Human leukocyte antigen haplotype and Fcgamma receptor polymorphisms are possible
targets of the relevant research.
PMID- 28419060
TI - Relationship of Hospital Costs With Mortality in Pediatric Critical Care: A Multi
Institutional Analysis.
AB - OBJECTIVE: With increasing emphasis on high "value" care, we designed this study
to evaluate the relationship between hospital costs and patient outcomes in
pediatric critical care. DESIGN: Post hoc analysis of data from an existing
administrative national database, Pediatric Health Information Systems.
Multivariable mixed effects logistic regression models were fitted to evaluate
association of hospital cost tertiles with odds of mortality after adjusting for
patient and center characteristics. SETTING: Forty-seven children's hospitals
across the United States. PATIENTS: Patients 18 years old or younger admitted to
a PICU at a Pediatric Health Information Systems participating hospital were
included (2004-2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total
of 917,663 patients from 47 hospitals were included. Median cost per patient was
$42,181 in the low-cost hospitals (341,689 patients, 16 hospitals), $56,806 in
the middle-cost hospitals (310,293 patients, 16 hospitals), and $82,588 in the
high-cost hospitals (265,681 patients, 15 hospitals). In unadjusted analysis,
patients cared for in the high-cost tertile hospitals were younger in age,
associated with more comorbidities, had higher resource utilization (including
extracorporeal membrane oxygenation and nitric oxide), had higher prevalence of
cardiac arrest, and were associated with worse outcomes (including mortality). In
adjusted analysis, high-cost tertile hospitals were not associated with improved
mortality, when compared with low- and medium-cost tertile hospitals (low cost vs
high cost: odds ratio, 0.99; 95% CI, 0.79-1.25 and middle cost vs high cost: odds
ratio, 1.10; 95% CI, 0.86-1.41). When stratified by diagnoses category, we noted
similar trends among cardiac and noncardiac patients. CONCLUSIONS: This large
observational study did not demonstrate any relationship between hospital costs
and patient outcomes in children with critical illness. Further efforts are
needed to evaluate quality-cost relationship and high value care in critically
ill children across centers of varying volume by linking data from clinical and
administrative databases.
PMID- 28419061
TI - Functional Status of Neonatal and Pediatric Patients After Extracorporeal
Membrane Oxygenation.
AB - OBJECTIVES: To describe functional status at hospital discharge for neonatal and
pediatric patients treated with extracorporeal membrane oxygenation, and identify
factors associated with functional status and mortality. DESIGN: Secondary
analysis of observational data collected by the Collaborative Pediatric Critical
Care Research Network between December 2012 and September 2014. SETTING: Eight
hospitals affiliated with the Collaborative Pediatric Critical Care Research
Network. PATIENTS: Patients were less than 19 years old and treated with
extracorporeal membrane oxygenation. INTERVENTIONS: Functional status was
evaluated among survivors using the Functional Status Scale. Total Functional
Status Scale scores range from 6 to 30 and are categorized as 6-7 (good), 8-9
(mildly abnormal), 10-15 (moderately abnormal), 16-21 (severely abnormal), and
greater than 21 (very severely abnormal). MEASUREMENTS AND MAIN RESULTS: Of 514
patients, 267 (52%) were neonates (<= 30 d old). Indication for extracorporeal
membrane oxygenation was respiratory for 237 (46%), cardiac for 207 (40%), and
extracorporeal cardiopulmonary resuscitation for 70 (14%). Among 282 survivors,
89 (32%) had good, 112 (40%) mildly abnormal, 67 (24%) moderately abnormal, and
14 (5%) severely or very severely abnormal function at hospital discharge. Among
neonates, development of renal failure and longer hospitalization were
independently associated with worse Functional Status Scale. Chronic conditions,
prematurity, venoarterial extracorporeal membrane oxygenation, increased red cell
transfusion in the first 24 hours of extracorporeal membrane oxygenation, and
longer extracorporeal membrane oxygenation duration were independently associated
with mortality. Among pediatric patients, chronic neurologic conditions,
tracheostomy or home ventilator, extracorporeal cardiopulmonary resuscitation,
hepatic dysfunction, and longer ICU stay were independently associated with worse
Functional Status Scale. Chronic cardiac conditions, hepatic dysfunction, and
neurologic or thrombotic complications were independently associated with
mortality. Achieving blood lactate concentration less than or equal to 2 mmol/L
during extracorporeal membrane oxygenation was independently associated with
survival in both neonatal and pediatric patients. CONCLUSIONS: In this study,
about half of extracorporeal membrane oxygenation patients survived with good,
mildly abnormal, or moderately abnormal function at hospital discharge. Patient
and extracorporeal membrane oxygenation-related factors are associated with
functional status and mortality.
PMID- 28419062
TI - Single-Center Study Investigating Foreign Language Acquisition at School in
Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants
in the Swiss German Population.
AB - OBJECTIVE: To evaluate foreign language acquisition at school in cochlear implant
patients. STUDY DESIGN: Cohort study. SETTING: CI center. PATIENTS: Forty three
cochlear implants (CI) patients (10-18 yr) were evaluated. CI nonusers and
patients with CI-explantation, incomplete datasets, mental retardation, or
concomitant medical disorders were excluded. INTERVENTION(S): Additional data
(type of schooling, foreign language learning, and bilingualism) were obtained
with questionnaires. German-speaking children with foreign tuition language
(English and/or French) at school were enrolled for further testing. MAIN OUTCOME
MEASURE(S): General patient data, auditory data, and foreign language data from
both questionnaires and tests were collected and analyzed. RESULTS: Thirty seven
out of 43 questionnaires (86%) were completed. Sixteen (43%) were in mainstream
education. Twenty-seven CI users (73%) have foreign language learning at school.
Fifteen of these were in mainstream education (55%), others in special schooling.
From 10 CI users without foreign language learning, one CI user was in mainstream
education (10%) and nine patients (90%) were in special schooling. Eleven German
speaking CI users were further tested in English and six additionally in French.
For reading skills, the school objectives for English were reached in 7 of 11
pupils (64%) and for French in 3 of 6 pupils (50%). For listening skills, 3 of 11
pupils (27%) reached the school norm in English and none in French. CONCLUSIONS:
Almost 75% of our CI users learn foreign language(s) at school. A small majority
of the tested CI users reached the current school norm for in English and French
in reading skills, whereas for hearing skills most of them were not able to reach
the norm.
PMID- 28419063
TI - The Effect of Elevated Intracranial Pressure on Frequency Tuning of Air-Conducted
Ocular Vestibular Myogenic Potentials in Meniere's Disease Patients.
AB - OBJECTIVE: To investigate the effect of increased intracranial pressure on ocular
vestibular-evoked myogenic potential (oVEMP) amplitudes and frequency tuning in
patients with Meniere's disease (MD) to elucidate whether oVEMPS recorded under
such conditions could provide a simple and accurate diagnostic test for MD.
SETTING: Tertiary referral center for otology and neurotology. PATIENTS: Ten
patients with certain unilateral MD (mean age = 48.2 yr, range 25-75 yr, 6 males
and 4 females) as confirmed by a locally enhanced inner ear MRI (LEIM) were
enrolled in this study. DESIGN: Air-conducted tone-burst oVEMP amplitudes were
measured in response to 500 Hz and 1000 Hz in the horizontal plane (0 degree), a
20-degree head-down position. RESULTS: Tilting the patients from the horizontal
position to the 20-degree head-down position led to a large reduction in oVEMP
amplitudes to the 500 Hz tone burst (3.02 MUV vs 1.17 MUV, p = 0.005) and to a
smaller one in the 1000 Hz tone burst (2.28 MUV vs 1.78 MUV, p = 0.013) in the
Meniere's ear. Accordingly, the 500/1000 Hz frequency-tuning ratio was
significantly decreased in the Meniere's ear as a result of this manoeuver (1.36
vs 0.75, p = 0.005). CONCLUSION: oVEMP amplitudes and frequency tuning in MD
patients show a similar behavior to that found in healthy control subjects. oVEMP
testing of putative MD patients in the tilted position is therefore unlikely to
be diagnostically useful.
PMID- 28419064
TI - The Application of Next-Generation Sequencing for Mutation Detection in Autosomal
Dominant Hereditary Hearing Impairment.
AB - OBJECTIVE: Identification of the causative mutation using next-generation
sequencing in autosomal-dominant hereditary hearing impairment, as mutation
analysis in hereditary hearing impairment by classic genetic methods, is hindered
by the high heterogeneity of the disease. PATIENTS: Two Swiss families with
autosomal-dominant hereditary hearing impairment. INTERVENTION: Amplified DNA
libraries for next-generation sequencing were constructed from extracted genomic
DNA, derived from peripheral blood, and enriched by a custom-made sequence
capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq
instrument, 300 cycles and paired-end sequencing. Technical data analysis was
performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The
detection of mutations in genes related to hearing loss by next-generation
sequencing was subsequently confirmed using specific polymerase-chain-reaction
and Sanger sequencing. MAIN OUTCOME MEASURE: Mutation detection in hearing-loss
related genes. RESULTS: The first family harbored the mutation c.5383+5delGTGA in
the TECTA-gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG
in the WFS1-gene and a second mutation TCOF1-c.1028G>A were identified.
CONCLUSION: Next-generation sequencing successfully identified the causative
mutation in families with autosomal-dominant hereditary hearing impairment. The
results helped to clarify the pathogenic role of a known mutation and led to the
detection of a novel one. NGS represents a feasible approach with great potential
future in the diagnostics of hereditary hearing impairment, even in smaller labs.
PMID- 28419065
TI - Late maternal age at last childbirth and telomere homeostasis.
PMID- 28419066
TI - Should postmenopausal women eat more protein? Or do the elite just exercise and
eat better?
PMID- 28419067
TI - Clinical use of ring with support pessary for advanced pelvic organ prolapse and
predictors of its short-term successful use.
AB - OBJECTIVE: This study aimed to evaluate the success rate, patient satisfaction
and adverse events with the use of the ring with support pessary in patients with
advanced pelvic organ prolapse (POP), and to identify the factors associated with
successful pessary use. METHODS: In this prospective study, 151 patients with
symptomatic advanced POP (POP quantification stage III/IV) came to the Centre of
Obstetrics and Gynaecology, Peking Union Medical College Hospital, for POP
treatment between May 2015 and December 2015. In all, 97 patients who chose the
ring with support pessaries were included in this study. Successful pessary use
was defined as the continuous use of the pessary at a 3-month follow-up visit.
Independent-samples t tests, nonparametric tests, chi-square tests, Fisher's
exact test, and logistic regression were used for data analysis. RESULTS: In all,
82 patients continued to use the ring with support pessary for 3 months, whereas
15 patients discontinued, corresponding to a success rate of 84.5% (82/97). Most
patients (80/82, 97.6%) who achieved success using the ring with support pessary
felt satisfied. No severe complications were observed. Size 3 was the most
commonly used size in our center (59.8% of the study patients). Predominant
anterior wall prolapse was associated with the successful use of ring with
support pessary (odds ratio 5.08, 95% confidence interval 1.33-19.43, P = 0.02).
CONCLUSIONS: The ring with support pessary was successfully used for the
treatment of advanced POP with high rates of success and satisfaction. A
predominant prolapse in the anterior wall may be a potential influence factor for
successful pessary use.
PMID- 28419068
TI - Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a
double-blind, placebo-controlled trial.
AB - OBJECTIVE: To evaluate the response of the vaginal mucosa with TX-004HR and its
correlation with vulvar and vaginal atrophy (VVA) symptoms, and whether visual
examination is a useful measure for assessing VVA. METHODS: REJOICE was a 12
week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of
a vaginal, muco-adhesive, 17beta-estradiol softgel capsule (TX-004HR 4, 10, and
25 MUg) in postmenopausal women with VVA and moderate-to-severe dyspareunia.
Treatments were self-administered vaginally once per day for 2 weeks, then twice
per week for 10 weeks. The vagina was visually examined at baseline and at weeks
2, 6, 8, and 12; changes were evaluated using a 4-item scale for vaginal color,
vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal
secretions. RESULTS: Significant improvements were observed with all three TX
004HR doses versus placebo in vaginal color (least square mean score changes of
0.96 to -1.06 for TX-004HR doses vs -0.60 for placebo at week 12), epithelial
integrity (-0.97 to -1.07 vs -0.60), epithelial surface thickness (-0.94 to -1.03
vs -0.61), and secretions (-1.01 to -1.06 vs -0.64) (P < 0.001 for all
comparisons at all time points). Both Pearson's correlations and logistic
regression receiver-operating characteristic curve analyses significantly
correlated the sum of the individual visual assessment scores with dyspareunia (P
< 0.0001) and vaginal dryness (P < 0.0001) at 12 weeks. CONCLUSIONS: Greater
improvements in the vaginal mucosa of postmenopausal women with VVA and moderate
to-severe dyspareunia were observed with TX-004HR versus placebo, and vaginal
mucosa assessment scores correlated with vaginal symptoms of dyspareunia and
dryness. Visual vaginal assessment by healthcare professionals is a useful
measure for diagnosing VVA and assessing response to treatment.
PMID- 28419070
TI - Another link between exercise and relief from postmenopausal decline.
PMID- 28419069
TI - Postmenopausal sleep disturbance and sexual dysfunction.
PMID- 28419071
TI - Reduction of cardiovascular risk with evolocumab (Repatha).
PMID- 28419072
TI - Dupilumab (Dupixent) for moderate to severe atopic dermatitis.
PMID- 28419073
TI - Plecanatide (Trulance) for chronic idiopathic constipation.
PMID- 28419074
TI - Arymo ER--a new abuse-deterrent morphine formulation.
PMID- 28419075
TI - In brief: New adult immunization recommendations.
PMID- 28419076
TI - In brief: Pancreatitis with eluxadoline (Viberzi) in patients without a
gallbladder.
PMID- 28419077
TI - OTC fluticasone furoate nasal spray (Flonase Sensimist) for allergic rhinitis.
PMID- 28419078
TI - Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis.
AB - BACKGROUND: MicroRNAs (miRs) are involved in the regulation of many processes
that contribute to malignancy, including cell proliferation, radiation
resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated
in breast cancer, remains unclear. METHODS: We examine the association of miR-330
3p with distant relapse-free survival in the Oxford cohort of breast cancer
patients. We also study miR-330-3p function using in vitro invasion and ex ovo
metastasis assays. Using in vitro luciferase assays, we validate a novel target
gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1). We
assess functional consequences of CCBE1 loss by using siRNA-mediated knockdown
followed by in vitro invasion assays. Lastly, we examine the expression profile
of CCBE1 in breast carcinomas in the Curtis and TCGA Breast Cancer data sets
using Oncomine Platform as well as distant relapse-free and overall survival of
patients in the Helsinki University breast cancer data set according to CCBE1
expression status. RESULTS: miR-330-3p is enriched in breast cancer, and higher
levels of miR-330-3p expression are associated with lower distant relapse-free
survival in a cohort of breast cancer patients. Consistent with these
observations, overexpression of miR-330-3p in breast cancer cell lines results in
greater invasiveness in vitro, and miR-330-3p-overexpressing cells also
metastasise more aggressively ex ovo. We identify CCBE1 as a direct target of miR
330-3p, and show that knockdown of CCBE1 results in a greater invasive capacity.
Accordingly, in breast cancer patients CCBE1 is frequently downregulated, and its
loss is associated with reduced distant relapse-free and overall survival.
CONCLUSIONS: We show for the first time that miR-330-3p targets CCBE1 to promote
invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers
in breast cancer.
PMID- 28419080
TI - Heteromolecular phases: Opposite interaction matters.
PMID- 28419079
TI - Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment
diffuse optical spectroscopic texture analysis.
AB - BACKGROUND: Diffuse optical spectroscopy (DOS) has been demonstrated capable of
monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast
cancer (LABC) patients. In this study, we evaluate texture features of
pretreatment DOS functional maps for predicting LABC response to NAC. METHODS:
Locally advanced breast cancer patients (n=37) underwent DOS breast imaging
before starting NAC. Breast tissue parametric maps were constructed and texture
analyses were performed based on grey-level co-occurrence matrices for feature
extraction. Ground truth labels as responders (R) or non-responders (NR) were
assigned to patients based on Miller-Payne pathological response criteria. The
capability of DOS textural features computed on volumetric tumour data before the
start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was
evaluated using a leave-one-out validation scheme at subject level. Data were
analysed using a logistic regression, naive Bayes, and k-nearest neighbour
classifiers. RESULTS: Data indicated that textural characteristics of
pretreatment DOS parametric maps can differentiate between treatment response
outcomes. The HbO2 homogeneity resulted in the highest accuracy among univariate
parameters in predicting response to chemotherapy: sensitivity (%Sn) and
specificity (%Sp) were 86.5% and 89.0%, respectively, and accuracy was 87.8%. The
highest predictors using multivariate (binary) combination features were the Hb
contrast+HbO2-homogeneity, which resulted in a %Sn/%Sp=78.0/81.0% and an accuracy
of 79.5%. CONCLUSIONS: This study demonstrated that the pretreatment DOS texture
features can predict breast cancer response to NAC and potentially guide
treatments.
PMID- 28419081
TI - Prepubertal children born large for gestational age have lower serum DHEAS
concentrations than those with a lower birth weight.
AB - BackgroundChildren born small for gestational age (SGA) have higher serum
dehydroepiandrosterone sulfate (DHEAS) concentrations than children born
appropriate for gestational age (AGA). The overall metabolic risk associated with
birth weight is U-shaped, but it is not known whether children born large for
gestational age (LGA) have elevated serum DHEAS levels.MethodsA cohort of 49
children born LGA, 56 children born AGA, and 23 children born SGA were studied at
5-8 years of age. Anthropometric data at birth, at the age of 2 years, and at
examination were recorded. Fasting blood samples were collected for serum
analyses of DHEAS, insulin-like growth factor 1 (IGF-1), and insulin
concentrations.ResultsThe children born LGA had lower serum DHEAS levels adjusted
for body mass index (BMI) standard deviation score (SDS) and age than the rest of
the children. Lower birth weight SDS and higher weight gain during the first 2
years of life predicted higher serum DHEAS levels. Higher serum IGF-1 levels were
also associated with higher prevalence of adrenarchal DHEAS
levels.ConclusionBeing born LGA was associated with lower DHEAS levels, whereas
small birth size and early catch-up growth predicted higher levels. This suggests
that genetic or early epigenetic factors have an impact on adrenarche. IGF-1 may
be a mediator in this process.
PMID- 28419082
TI - Diffuse optical tomography to investigate the newborn brain.
AB - Over the past 15 years, functional near-infrared spectroscopy (fNIRS) has emerged
as a powerful technology for studying the developing brain. Diffuse optical
tomography (DOT) is an extension of fNIRS that combines hemodynamic information
from dense optical sensor arrays over a wide field of view. Using image
reconstruction techniques, DOT can provide images of the hemodynamic correlates
to neural function that are comparable to those produced by functional magnetic
resonance imaging. This review article explains the principles of DOT, and
highlights the growing literature on the use of DOT in the study of healthy
development of the infant brain, and the study of novel pathophysiology in
infants with brain injury. Current challenges, particularly around
instrumentation and image reconstruction, will be discussed, as will the future
of this growing field, with particular focus on whole-brain, time-resolved DOT.
PMID- 28419083
TI - Pneumococcal vaccination and efficacy in patients with heterotaxy syndrome.
AB - BackgroundPneumococcal vaccines, including pneumococcal polysaccharide vaccine
(PPV) and pneumococcal conjugated vaccine (PCV), are crucial in preventing
invasive pneumococcal diseases. We analyzed the pneumococcal vaccination rate,
efficacy, and durability in patients with heterotaxy.MethodsAll patients with
heterotaxy and CCHD who were followed up at our institution between 2010 and 2015
were included. Pneumococcal vaccine status and geometric mean concentration (GMC)
of serotypes 6B, 14, 19F, and 23F were analyzed. Splenic function was considered
abnormal when the percentage of IgM memory B cell was less than 1%.ResultsThe
GMCs of the four serotypes did not differ significantly between patients with
heterotaxy and those with CCHD; the GMCs were also not affected by abnormal
splenic function. Most patients had GMCs >0.35 MUg/ml (protection level) 4-5
years after either PPV or PCV injection; however, it may decay gradually in some
serotypes. In addition, 21.4% of 42 patients with heterotaxy did not receive
pneumococcal vaccine, and none completely adhered to the vaccine
guidelines.ConclusionsVaccine efficacy was acceptable, even in patients with
abnormal splenic function. In some patients, the durability of PPV and PCV
decreased with time, highlighting the importance of booster doses. Vaccination
rate in patients with heterotaxy is unsatisfactory.
PMID- 28419084
TI - Neonatal resuscitation in global health settings: an examination of the past to
prepare for the future.
AB - As rates of childhood mortality decline, neonatal deaths account for nearly half
of under-5 deaths worldwide. Intrapartum-related events (birth asphyxia)
contribute to approximately one-quarter of neonatal deaths, many of which can be
prevented by simple resuscitation and newborn care interventions. This paper
reviews various lines of research that have influenced the global neonatal
resuscitation landscape. A brief situational analysis of asphyxia-related newborn
mortality in low-resource settings is linked to renewed efforts to reduce
neonatal mortality in the Every Newborn Action Plan. Possible solutions to gaps
in care are identified. Building on international scientific evidence, tests of
educational efficacy, and community-based trials established the feasibility and
effectiveness of training in resource-limited settings and identified successful
implementation strategies. Implementation of neonatal resuscitation programs has
been shown to decrease intrapartum stillbirth rates and early neonatal mortality.
Challenges remain with respect to provider competencies, coverage, and quality of
interventions. The combination of resuscitation science, strategies to increase
educational effectiveness, and implemention of interventions with high coverage
and quality has resulted in reduced rates of asphyxia-related neonatal mortality.
Further efforts to improve coverage and implementation of neonatal resuscitation
will be necessary to meet the 2035 goal of eliminating preventable newborn
deaths.
PMID- 28419085
TI - Neonatal outcomes of moderately preterm infants compared to extremely preterm
infants.
AB - BackgroundExtremely preterm infants (EPT, <29 weeks' gestation) represent only
0.9% of births in the United States; yet these infants are the focus of most
published research. Moderately preterm neonates (MPT, 29-336/7 weeks) are an
understudied group of high-risk infants.MethodsTo determine the neonatal outcomes
of MPT infants across the gestational age spectrum, and to compare these with EPT
infants. A prospective observational cohort was formed in 18 level 3-4 neonatal
intensive care units (NICUs) in the Eunice Kennedy Shriver NICHD Neonatal
Research Network. Participants included all MPT infants admitted to NICUs and all
EPT infants born at sites between January 2012 and November 2013. Antenatal
characteristics and neonatal morbidities were abstracted from records using pre
specified definitions by trained neonatal research nurses.ResultsMPT infants
experienced morbidities similar to, although at lower rates than, those of EPT
infants. The main cause of mortality was congenital malformation, accounting for
43% of deaths. Central Nervous System injury occurred, including intraventricular
hemorrhage. Most MPT infants required respiratory support, but sequelae such as
bronchopulmonary dysplasia were rare. The primary contributors to hospitalization
beyond 36 weeks' gestation were inability to achieve adequate oral intake and
persistent apnea.ConclusionsMPT infants experience morbidity and prolonged
hospitalization. Such morbidity deserves focused research to improve therapeutic
and prevention strategies.
PMID- 28419086
TI - Low birth weight is associated with impaired murine kidney development and
function.
AB - BackgroundLow birth weight (LBW) neonates have impaired kidney development that
leaves them susceptible to kidney disease and hypertension during adulthood. The
study here identifies events that blunt nephrogenesis and kidney development in
the murine LBW neonate.MethodsWe examined survival, kidney development, GFR, gene
expression, and cyto-/chemokines in the LBW offspring of malnourished (caloric
and protein-restricted) pregnant mice.ResultsMalnourished pregnant mothers gave
birth to LBW neonates that had 40% reduced body weight and 54% decreased
survival. Renal blood perfusion was reduced by 37%, whereas kidney volume and GFR
were diminished in the LBW neonate. During gestation, the LBW neonatal kidney had
2.2-fold increased apoptosis, 76% decreased SIX2+ progenitor cells,
downregulation of mesenchymal-to-epithelial signaling factors Wnt9b and Fgf8, 64%
less renal vesicle formation, and 32% fewer nephrons than controls. At birth,
increased plasma levels of IL-1beta, IL-6, IL-12(p70), and granulocyte-macrophage
colony-stimulating factor in the LBW neonate reduced SIX2+ progenitor
cells.ConclusionIncreased pro-inflammatory cytokines in the LBW neonate decrease
SIX2+ stem cells in the developing kidney. Reduced renal stem cells (along with
the decreased mesenchymal-to-epithelial signaling) blunt renal vesicle
generation, nephron formation, and kidney development. Subsequently, the mouse
LBW neonate has reduced glomeruli volume, renal perfusion, and GFR.
PMID- 28419087
TI - Novel targeted therapy for neuroblastoma: silencing the MXD3 gene using siRNA.
AB - BackgroundNeuroblastoma is the second most common extracranial cancer in
children. Current therapies for neuroblastoma, which use a combination of
chemotherapy drugs, have limitations for high-risk subtypes and can cause
significant long-term adverse effects in young patients. Therefore, a new therapy
is needed. In this study, we investigated the transcription factor MXD3 as a
potential therapeutic target in neuroblastoma.MethodsMXD3 expression was analyzed
in five neuroblastoma cell lines by immunocytochemistry and quantitative real
time reverse transcription PCR, and in 18 primary patient tumor samples by
immunohistochemistry. We developed nanocomplexes using siRNA and
superparamagnetic iron oxide nanoparticles to target MXD3 in neuroblastoma cell
lines in vitro as a single-agent therapeutic and in combination with doxorubicin,
vincristine, cisplatin, or maphosphamide-common drugs used in current
neuroblastoma treatment.ResultsMXD3 was highly expressed in neuroblastoma cell
lines and in patient tumors that had high-risk features. Neuroblastoma cells
treated in vitro with the MXD3 siRNA nanocomplexes showed MXD3 protein knockdown
and resulted in cell apoptosis. Furthermore, on combining MXD3 siRNA
nanocomplexes with each of the four drugs, all showed additive
efficacy.ConclusionThese results indicate that MXD3 is a potential new target and
that the use of MXD3 siRNA nanocomplexes is a novel therapeutic approach for
neuroblastoma.
PMID- 28419088
TI - The SnRK2 kinases modulate miRNA accumulation in Arabidopsis.
AB - MicroRNAs (miRNAs) regulate gene expression and play critical roles in growth and
development as well as stress responses in eukaryotes. miRNA biogenesis in plants
requires a processing complex that consists of the core components DICER-LIKE 1
(DCL1), SERRATE (SE) and HYPONASTIC LEAVES (HYL1). Here we show that inactivation
of functionally redundant members of the SnRK2 kinases, which are the core
components of abscisic acid (ABA) and osmotic stress signaling pathways, leads to
reduction in miRNA accumulation under stress conditions. Further analysis
revealed that the steady state level of HYL1 protein in plants under osmotic
stress is dependent on the SnRK2 kinases. Additionally, our results suggest that
the SnRK2 kinases physically associate with the miRNA processing components SE
and HYL1 and can phosphorylate these proteins in vitro. These findings reveal an
important role for the SnRK2 kinases in the regulation of miRNA accumulation and
establish a mechanism by which ABA and osmotic stress signaling is linked to
miRNA biogenesis.
PMID- 28419089
TI - Erroneous energy-generating cycles in published genome scale metabolic networks:
Identification and removal.
AB - Energy metabolism is central to cellular biology. Thus, genome-scale models of
heterotrophic unicellular species must account appropriately for the utilization
of external nutrients to synthesize energy metabolites such as ATP. However,
metabolic models designed for flux-balance analysis (FBA) may contain
thermodynamically impossible energy-generating cycles: without nutrient
consumption, these models are still capable of charging energy metabolites (such
as ADP->ATP or NADP+->NADPH). Here, we show that energy-generating cycles occur
in over 85% of metabolic models without extensive manual curation, such as those
contained in the ModelSEED and MetaNetX databases; in contrast, such cycles are
rare in the manually curated models of the BiGG database. Energy generating
cycles may represent model errors, e.g., erroneous assumptions on reaction
reversibilities. Alternatively, part of the cycle may be thermodynamically
feasible in one environment, while the remainder is thermodynamically feasible in
another environment; as standard FBA does not account for thermodynamics,
combining these into an FBA model allows erroneous energy generation. The
presence of energy-generating cycles typically inflates maximal biomass
production rates by 25%, and may lead to biases in evolutionary simulations. We
present efficient computational methods (i) to identify energy generating cycles,
using FBA, and (ii) to identify minimal sets of model changes that eliminate
them, using a variant of the GlobalFit algorithm.
PMID- 28419090
TI - The co-existence of transcriptional activator and transcriptional repressor MEF2
complexes influences tumor aggressiveness.
AB - The contribution of MEF2 TFs to the tumorigenic process is still mysterious. Here
we clarify that MEF2 can support both pro-oncogenic or tumor suppressive
activities depending on the interaction with co-activators or co-repressors
partners. Through these interactions MEF2 supervise histone modifications
associated with gene activation/repression, such as H3K4 methylation and H3K27
acetylation. Critical switches for the generation of a MEF2 repressive
environment are class IIa HDACs. In leiomyosarcomas (LMS), this two-faced trait
of MEF2 is relevant for tumor aggressiveness. Class IIa HDACs are overexpressed
in 22% of LMS, where high levels of MEF2, HDAC4 and HDAC9 inversely correlate
with overall survival. The knock out of HDAC9 suppresses the transformed
phenotype of LMS cells, by restoring the transcriptional proficiency of some MEF2
target loci. HDAC9 coordinates also the demethylation of H3K4me3 at the promoters
of MEF2-target genes. Moreover, we show that class IIa HDACs do not bind all the
regulative elements bound by MEF2. Hence, in a cell MEF2-target genes actively
transcribed and strongly repressed can coexist. However, these repressed MEF2
targets are poised in terms of chromatin signature. Overall our results candidate
class IIa HDACs and HDAC9 in particular, as druggable targets for a therapeutic
intervention in LMS.
PMID- 28419091
TI - Multidrug-resistant bacteria compensate for the epistasis between resistances.
AB - Mutations conferring resistance to antibiotics are typically costly in the
absence of the drug, but bacteria can reduce this cost by acquiring compensatory
mutations. Thus, the rate of acquisition of compensatory mutations and their
effects are key for the maintenance and dissemination of antibiotic resistances.
While compensation for single resistances has been extensively studied,
compensatory evolution of multiresistant bacteria remains unexplored.
Importantly, since resistance mutations often interact epistatically,
compensation of multiresistant bacteria may significantly differ from that of
single-resistant strains. We used experimental evolution, next-generation
sequencing, in silico simulations, and genome editing to compare the compensatory
process of a streptomycin and rifampicin double-resistant Escherichia coli with
those of single-resistant clones. We demonstrate that low-fitness double
resistant bacteria compensate faster than single-resistant strains due to the
acquisition of compensatory mutations with larger effects. Strikingly, we
identified mutations that only compensate for double resistance, being neutral or
deleterious in sensitive or single-resistant backgrounds. Moreover, we show that
their beneficial effects strongly decrease or disappear in conditions where the
epistatic interaction between resistance alleles is absent, demonstrating that
these mutations compensate for the epistasis. In summary, our data indicate that
epistatic interactions between antibiotic resistances, leading to large fitness
costs, possibly open alternative paths for rapid compensatory evolution, thereby
potentially stabilizing costly multiple resistances in bacterial populations.
PMID- 28419092
TI - A multi-centric Study of Candida bloodstream infection in Lima-Callao, Peru:
Species distribution, antifungal resistance and clinical outcomes.
AB - BACKGROUND: The incidence of candidemia is increasing in developing countries.
Very little is known about the epidemiology of candidemia in Peru. The aim of
this study is to describe the incidence, microbiology, clinical presentation and
outcomes of Candida bloodstream infections in three Lima-Callao hospitals.
METHODS: Candida spp. isolates were identified prospectively at participant
hospitals between November 2013 and January 2015. Susceptibility testing for
amphotericin B, fluconazole, posaconazole, voriconazole and anidulafungin was
performed using broth microdilution method. Clinical information was obtained
from medical records and evaluated. RESULTS: We collected information on 158
isolates and 157 patients. Median age of patients was 55.0 yrs., and 64.1% were
males. Thirty-eight (24.2%) episodes of candidemia occurred in those <18 yrs. The
frequency of non-Candida albicans was 72.1%. The most frequently recovered
species were C. albicans (n = 44, 27.8%), C. parapsilosis (n = 40, 25.3%), C.
tropicalis (n = 39, 24.7%) and C. glabrata (n = 15, 9.5%). Only four isolates
were resistant to fluconazole, 86.7% (n = 137) were susceptible and 17 were
susceptible-dose dependent. Decreased susceptibility to posaconazole was also
observed in three isolates, and one to voriconazole. All isolates were
susceptible to anidulafungin and amphotericin B. The most commonly associated co
morbid conditions were recent surgery (n = 61, 38.9%), mechanical ventilation (n
= 60, 38.2%) and total parenteral nutrition (n = 57, 36.3%). The incidence of
candidemia by center ranged between 1.01 and 2.63 cases per 1,000 admissions,
with a global incidence of 2.04. Only 28.1% of cases received treatment within 72
hrs. of diagnosis. Overall, the 30-day survival was 60.4% (treated subjects,
67.4%; not-treated patients, 50.9%). CONCLUSIONS: We found a very high proportion
of non-albicans Candida species. Despite this, the decreased
susceptibility/resistance to fluconazole was only 13.3% and not seen in the other
antifungals. Overall, the incidence of candidemia mortality was high when
compared to other international studies. It is possible, that the delay in
initiating antifungal treatment contributed to the elevated mortality rate, in
spite of low antifungal resistance.
PMID- 28419093
TI - Microhomology-mediated end joining induces hypermutagenesis at breakpoint
junctions.
AB - Microhomology (MH) flanking a DNA double-strand break (DSB) drives chromosomal
rearrangements but its role in mutagenesis has not yet been analyzed. Here we
determined the mutation frequency of a URA3 reporter gene placed at multiple
locations distal to a DSB, which is flanked by different sizes (15-, 18-, or 203
bp) of direct repeat sequences for efficient repair in budding yeast. Induction
of a DSB accumulates mutations in the reporter gene situated up to 14-kb distal
to the 15-bp MH, but more modestly to those carrying 18- and 203-bp or no
homology. Increased mutagenesis in MH-mediated end joining (MMEJ) appears coupled
to its slower repair kinetics and the extensive resection occurring at flanking
DNA. Chromosomal translocations via MMEJ also elevate mutagenesis of the flanking
DNA sequences 7.1 kb distal to the breakpoint junction as compared to those
without MH. The results suggest that MMEJ could destabilize genomes by triggering
structural alterations and increasing mutation burden.
PMID- 28419094
TI - An open source pharma roadmap.
AB - In an Essay, Matthew Todd and colleagues discuss an open source approach to drug
development.
PMID- 28419096
TI - Determinants of neonatal mortality in rural Northern Ethiopia: A population based
nested case control study.
AB - INTRODUCTION: In low income and middle income countries, neonatal mortality
remains high despite the gradual reduction in under five mortality. Newborn death
contributes for about 38% of all under five deaths. This study has identified the
magnitude and independent predictors of neonatal mortality in rural Ethiopia.
METHODS: This population based nested case control study was conducted in rural
West Gojam zone, Northern Ethiopia, among a cohort of pregnant women who gave
birth between March 2011 and Feb 2012. The cohort was established by Maternal and
Newborn Health in Ethiopia Partnership (MaNHEP) project in 2010 by recruiting
mothers in their third trimester, as identified by trained community volunteers.
Once identified, women stayed in the cohort throughout their pregnancy period
receiving Community Maternal and Newborn Health (CMNH) training by health
extension workers and community volunteers till the end of the first 48 hours
postpartum. Cases were 75 mothers who lost their newborns to neonatal death and
controls were 150 randomly selected mothers with neonates who survived the
neonatal period. Data to identify cause of death were collected using the WHO
standard verbal autopsy questionnaire after the culturally appropriate 40 days of
bereavement period. Binomial logistic regression model was used to identify
independent contributors to neonatal mortality. RESULT: The neonatal mortality
rate was AOR(95%CI) = 18.6 (14.8, 23.2) per 1000 live births. Neonatal mortality
declined with an increase in family size, neonates who were born among a family
of more than two had lesser odds of death in the neonatal period than those who
were born in a family of two AOR (95% CI) = 0.13 (0.02, 0.71). Mothers who gave
birth to 2-4 AOR(95%CI) = 0.15 (0.05, 0.48) and 5+ children AOR(95%CI) = 0.08
(0.02, 0.26) had lesser odds of losing their newborns to neonatal mortality.
Previous history of losing a newborn to neonatal death also increased the odds of
neonatal mortality during the last birth AOR (95%CI) = 0.25 (0.11, 0.53).
CONCLUSION: The neonatal mortality rate in our study was three times lower than
the regional neonatal mortality rate estimate, indicating community based
interventions could significantly decrease neonatal mortality. The identified
determinants, which are amenable for change, emphasize the need to improve
quality of care during pregnancy, labour and delivery to improve pregnancy
outcome.
PMID- 28419095
TI - Effectiveness of a live oral human rotavirus vaccine after programmatic
introduction in Bangladesh: A cluster-randomized trial.
AB - BACKGROUND: Rotavirus vaccines are now globally recommended by the World Health
Organization (WHO), but in early 2009 WHO's Strategic Advisory Group of Experts
on Immunization reviewed available data and concluded that there was no evidence
for the efficacy or effectiveness of a two-dose schedule of the human rotavirus
vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the
effectiveness of programmatic rotavirus vaccination, including possible indirect
effects, has not been assessed in low-resource populations in Asia. METHODS AND
FINDINGS: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab
Health and Demographic Surveillance System to include two doses of HRV with the
standard infant vaccines at 6 and 10 wk of age or to provide standard infant
vaccines without HRV. The study was initiated November 1, 2008, and surveillance
was conducted concurrently at Matlab Diarrhoea Hospital and two community
treatment centers to identify children less than 2 y of age presenting with acute
rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made
by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall
effectiveness of the HRV vaccination program (primary objective) was measured by
comparing the incidence rate of ARD among all children age-eligible for
vaccination in villages where HRV was introduced to that among such children in
villages where HRV was not introduced. Total effectiveness among vaccinees and
indirect effectiveness were also evaluated. In all, 6,527 infants were age
eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In
HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The
incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages
compared to 2.8 per 100 person-years in HRV villages, indicating an overall
effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV
against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point
estimate for total effectiveness was higher against ARD during the first year of
life than during the second (45.2% versus 28.9%), but estimates for the second
year of life lacked precision and did not reach statistical significance.
Indirect effects were not detected. To check for bias in presentation to
treatment facilities, we evaluated the effectiveness of HRV against acute
diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI,
46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious
adverse events were identified among recipients of HRV, but none were considered
related to receipt of study vaccine. The main limitation of this study is that it
was an open-label study with an observed-only control group (no placebo).
CONCLUSIONS: The two-dose HRV rotavirus vaccination program significantly reduced
medically attended ARD in this low-resource population in Asia. Protection among
vaccinees was similar to that in other low-resource settings. In low-resource
populations with high rotavirus incidence, large-scale vaccination across a wide
population may be required to obtain the full benefit of rotavirus vaccination,
including indirect effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00737503.
PMID- 28419097
TI - Clinical decision tools are needed to identify HIV-positive patients at high risk
for poor outcomes after initiation of antiretroviral therapy.
AB - Margaret McNairy and colleagues highlight the need for clinical decision tools to
help identify HIV patients who would benefit from tailored services to avoid poor
outcomes such as death and loss to follow-up.
PMID- 28419098
TI - Robust information propagation through noisy neural circuits.
AB - Sensory neurons give highly variable responses to stimulation, which can limit
the amount of stimulus information available to downstream circuits. Much work
has investigated the factors that affect the amount of information encoded in
these population responses, leading to insights about the role of covariability
among neurons, tuning curve shape, etc. However, the informativeness of neural
responses is not the only relevant feature of population codes; of potentially
equal importance is how robustly that information propagates to downstream
structures. For instance, to quantify the retina's performance, one must consider
not only the informativeness of the optic nerve responses, but also the amount of
information that survives the spike-generating nonlinearity and noise corruption
in the next stage of processing, the lateral geniculate nucleus. Our study
identifies the set of covariance structures for the upstream cells that optimize
the ability of information to propagate through noisy, nonlinear circuits. Within
this optimal family are covariances with "differential correlations", which are
known to reduce the information encoded in neural population activities. Thus,
covariance structures that maximize information in neural population codes, and
those that maximize the ability of this information to propagate, can be very
different. Moreover, redundancy is neither necessary nor sufficient to make
population codes robust against corruption by noise: redundant codes can be very
fragile, and synergistic codes can-in some cases-optimize robustness against
noise.
PMID- 28419099
TI - Getting ready to use control: Advances in the measurement of young children's use
of proactive control.
AB - A key developmental transition in executive function is in the temporal dynamics
of its engagement: children shift from reactively calling to mind task-relevant
information as needed, to being able to proactively maintain information across
time in anticipation of upcoming demands. This transition is important for
understanding individual differences and developmental changes in executive
function; however, methods targeting its assessment are limited. We tested the
possibility that Track-It, a paradigm developed to measure selective sustained
attention, also indexes proactive control. In this task children must track a
target shape as it moves unpredictably among moving distractors, and identify
where it disappears, which may require proactively maintaining information about
the target or goal. In two experiments (5-6 year-olds, Ns = 33, 64), children's
performance on Track-It predicted proactive control across two established
paradigms. These findings suggest Track-It measures proactive control in
children. Theoretical possibilities regarding how proactive control and selective
sustained attention may be related are also discussed.
PMID- 28419100
TI - Validation of two multiplex platforms to quantify circulating markers of
inflammation and endothelial injury in severe infection.
AB - Biomarkers can prognosticate outcome and enable risk-stratification. In severe
infection, focusing on multiple markers reflecting pathophysiological mechanisms
of organ injury could enhance management and pathway-directed therapeutics.
Limited data exist on the performance of multiplex biomarker platforms. Our goal
was to compare endothelial and immune activation biomarkers in severe pediatric
infections using two multiplex platforms. Frozen plasma from 410 children
presenting to the Jinja Regional Hospital in Uganda with suspected infection was
used to measure biomarkers of endothelial (Angiopoietin-2, sFlt-1, sVCAM-1, sICAM
1) and immune (IL-6, IP-10, sTNFR-1, CHI3L1) activation. Two multiplex platforms
(Luminex(r), EllaTM) based on monoclonal antibody sandwich immunoassays using
biotin-streptavidin conjugate chemistry were selected with reagents from R&D
Systems. The two platforms differed in ease and time of completion, number of
samples per assay, and dynamic concentration range. Intra-assay variability
assessed using a coefficient of variation (CV%) was 2.2-3.4 for Luminex(r) and
1.2-2.9 for EllaTM. Correlations for biomarker concentrations within dynamic
range of both platforms were best for IL-6 (rho = 0.96, p<0.0001), IP-10 (rho =
0.94, p<0.0001) and sFlt-1 (rho = 0.94, p<0.0001). Agreement between
concentrations obtained by both methods assessed by the Bland-Altman test varied,
with best agreement for CHI3L1. Our data suggest that biomarkers of endothelial
and immune activation can be readily measured with multiplex platforms.
Luminex(r) and EllaTM produced reliable results with excellent CV% values. The
EllaTM platform was more automated and completed in 75 minutes, potentially
compatible with near-patient use. Trends in concentrations obtained by these
methods were highly correlated, although absolute values varied, suggesting
caution is required when comparing data from different multiplex platforms.
PMID- 28419101
TI - Anti-proliferative effect of novel primary cetyl alcohol derived sophorolipids
against human cervical cancer cells HeLa.
AB - Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to display
anticancer activity. In the present study, we report anti-proliferative studies
on purified forms of novel SLs synthesized using cetyl alcohol as the substrate
(referred as SLCA) and their anticancer mechanism in human cervical cancer cells.
Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F)
was examined in panel of human cancer cell lines as well as primary cells. Among
these fractions, SLCA B and C significantly inhibited the survival of HeLa and
HCT 116 cells without affecting the viability of normal human umbilical vein
endothelial cells (HUVEC). The two fractions were identified as cetyl alcohol
sophorolipids with non-hydroxylated tail differing in the degree of acetylation
on sophorose head group. At an IC50 concentration SLCA B (16.32 MUg ml-1) and
SLCA C (14.14 MUg ml-1) blocked the cell cycle progression of HeLa cells at G1/S
phase in time-dependent manner. Moreover, SLCA B and SLCA C induced apoptosis in
HeLa cells through an increase in intracellular Ca2+ leading to depolarization of
mitochondrial membrane potential and increase in the caspase-3, -8 and -9
activity. All these findings suggest that these SLCAs could be explored for their
chemopreventive potential in cervical cancer.
PMID- 28419102
TI - Effect of genomic distance on coexpression of coregulated genes in E. coli.
AB - In prokaryotes, genomic distance is a feature that in addition to coregulation
affects coexpression. Several observations, such as genomic clustering of highly
coexpressed small regulons, support the idea that coexpression behavior of
coregulated genes is affected by the distance between the coregulated genes.
However, the specific contribution of distance in addition to coregulation in
determining the degree of coexpression has not yet been studied systematically.
In this work, we exploit the rich information in RegulonDB to study how the
genomic distance between coregulated genes affects their degree of coexpression,
measured by pairwise similarity of expression profiles obtained under a large
number of conditions. We observed that, in general, coregulated genes display
higher degrees of coexpression as they are more closely located on the genome.
This contribution of genomic distance in determining the degree of coexpression
was relatively small compared to the degree of coexpression that was determined
by the tightness of the coregulation (degree of overlap of regulatory programs)
but was shown to be evolutionary constrained. In addition, the distance effect
was sufficient to guarantee coexpression of coregulated genes that are located at
very short distances, irrespective of their tightness of coregulation. This is
partly but definitely not always because the close distance is also the cause of
the coregulation. In cases where it is not, we hypothesize that the effect of the
distance on coexpression could be caused by the fact that coregulated genes
closely located to each other are also relatively more equidistantly located from
their common TF and therefore subject to more similar levels of TF molecules. The
absolute genomic distance of the coregulated genes to their common TF-coding gene
tends to be less important in determining the degree of coexpression. Our results
pinpoint the importance of taking into account the combined effect of distance
and coregulation when studying prokaryotic coexpression and transcriptional
regulation.
PMID- 28419103
TI - Establishment of a tear protein biomarker panel differentiating between Graves'
disease with or without orbitopathy.
AB - BACKGROUND: Graves' orbitopathy (GO) is an autoimmune inflammatory ocular
complication and one of the most frequent manifestations of Graves' disease (GD).
Clinical judgment of GO is subjective sometimes leading to clinical and
therapeutic challenges. Better tools to diagnose this severe complication are
warranted. PATIENTS AND METHODS: The aim of the present study was to evaluate
tear levels of LYZ, LACRT and AZGP1 in GD patients with or without GO, as
possible biomarkers for GO. Tear samples were collected from GD patients with
moderate-to-severe GO (n = 21) and no clinical signs of GO (n = 21).
Additionally, 18 GD patients with mild GO and 9 patients without GO were included
in a further part of the study. RESULTS: Tear levels of LYZ (p < 0.001), LACRT (p
= 0.004) and AZGP1 (p = 0.001) were significantly elevated in GD patients with
moderate-to-severe GO compared to GD patients without GO. The discriminatory
power of the three biomarkers, combined in a panel was confirmed by ROC plot
analysis, with an AUC value of 0.93 (sensitivity of 95%; specificity of 80%).
Since LYZ showed the best performance in discriminating between GD patients with
(moderate-to-severe) and without GO (in combination with limited sample volume
available), LYZ levels were also measured in tears from GD patients with mild GO
and without GO. Significantly higher levels of LYZ were measured in GD patients
with mild GO compared to those without GO (p = 0.003). CONCLUSIONS: We have
established a novel three-protein biomarker panel that is able to discriminate
between GD patients with and without GO, which might aid in diagnostic evaluation
of GO as well as an indicator for disease activity.
PMID- 28419104
TI - Further characterisation of differences between TL and AB zebrafish (Danio
rerio): Gene expression, physiology and behaviour at day 5 of the larval stage.
AB - Zebrafish (Danio rerio) have become popular as model organism in research. Many
strains are readily available, which not only differ morphologically, but also
genetically, physiologically and behaviourally. Here, we focus on the AB and
Tupfel long-fin (TL) strain for which we have previously shown that adults differ
in baseline hypothalamus-pituitary-interrenal (HPI)-axis activity (AB higher than
TL) affecting inhibitory avoidance behaviour (absent in AB). To assess whether
strain differences are already present in early life stages, we compared baseline
HPI-axis related gene expression as well as cortisol levels, (neuro)development
related as well as (innate) immune system related gene expression, and light-dark
as well as startle behaviour in larvae 5 days post fertilisation. The data show
that AB and TL larvae differ in baseline HPI-axis activity (AB higher than TL),
expression of (neuro)development and immune system related genes (AB higher than
TL), habituation to acoustic/vibrational stimuli (AB habituate faster than TL)
and light-dark induced changes in motor behaviour (AB stronger than TL). Our data
show that already in larval stages differences exist between zebrafish of the AB
and TL strain confirming and extending data of earlier studies. To what extent
the mutation in connexin 41.8, leading to spots rather than stripes in TL, but
also (possibly) affecting eye, heart and brain function, is involved in the
expression of (some of) these differences needs to be studied. These results
emphasise that differences between strains need to be taken into account to
enhance reproducibility both within, and between, laboratories.
PMID- 28419105
TI - Year-round breeding equatorial Larks from three climatically-distinct populations
do not use rainfall, temperature or invertebrate biomass to time reproduction.
AB - Timing of reproduction in birds is important for reproductive success and is
known to depend on environmental cues such as day length and food availability.
However, in equatorial regions, where day length is nearly constant, other
factors such as rainfall and temperature are thought to determine timing of
reproduction. Rainfall can vary at small spatial and temporal scales, providing a
highly fluctuating and unpredictable environmental cue. In this study we
investigated the extent to which spatio-temporal variation in environmental
conditions can explain the timing of breeding of Red-capped Lark, Calandrella
cinerea, a species that is capable of reproducing during every month of the year
in our equatorial east African study locations. For 39 months in three
climatically-distinct locations, we monitored nesting activities, sampled ground
and flying invertebrates, and quantified rainfall, maximum (Tmax) and minimum
(Tmin) temperatures. Among locations we found that lower rainfall and higher
temperatures did not coincide with lower invertebrate biomasses and decreased
nesting activities, as predicted. Within locations, we found that rainfall, Tmax,
and Tmin varied unpredictably among months and years. The only consistent
annually recurring observations in all locations were that January and February
had low rainfall, high Tmax, and low Tmin. Ground and flying invertebrate
biomasses varied unpredictably among months and years, but invertebrates were
captured in all months in all locations. Red-capped Larks bred in all calendar
months overall but not in every month in every year in every location. Using
model selection, we found no clear support for any relationship between the
environmental variables and breeding in any of the three locations. Contrary to
popular understanding, this study suggests that rainfall and invertebrate biomass
as proxy for food do not influence breeding in equatorial Larks. Instead, we
propose that factors such as nest predation, female protein reserves, and
competition are more important in environments where weather and food meet
minimum requirements for breeding during most of the year.
PMID- 28419106
TI - Quality improvement intervention to increase adherence to ART prescription policy
at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.
AB - INTRODUCTION: In urban areas, crowded HIV treatment facilities with long patient
wait times can deter patients from attending their clinical appointments and
picking up their medications, ultimately disrupting patient care and compromising
patient retention and adherence. METHODS: Formative research at eight facilities
in Lusaka revealed that only 46% of stable HIV treatment patients were receiving
a three-month refill supply of antiretroviral drugs, despite it being national
policy for stable adult patients. We designed a quality improvement intervention
to improve the operationalization of this policy. We conducted a cluster
randomized controlled trial in sixteen facilities in Lusaka with the primary
objective of examining the intervention's impact on the proportion of stable
patients receiving three-month refills. The secondary objective was examining
whether the quality improvement intervention reduced facility congestion measured
through two proxy indicators: daily volume of clinic visits and average clinic
wait times for services. RESULTS: The mean change in the proportion of three
month refills among control facilities from baseline to endline was 10% (from 38%
to 48%), compared to a 25% mean change (an increase from 44% to 69%) among
intervention facilities. This represents a significant 15% mean difference (95%
CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three
month refills. On average, control facilities had 15 more visits per day in the
endline than in the baseline, while intervention facilities had 20 fewer visits
per day in endline than in baseline, a mean difference of 35 fewer visits per day
(P = 0.1). The change in the mean facility total wait time for intervention
facilities dropped 19 minutes between baseline and endline when compared to
control facilities (95% CI: -10.2-48.5; P = 0.2). CONCLUSION: A more patient
centred service delivery schedule of three-month prescription refills for stable
patients is viable. We encourage the expansion of this sustainable intervention
in Zambia's urban clinics.
PMID- 28419107
TI - Characterization of a transgenic mouse model exhibiting spontaneous lung
adenocarcinomas with a metastatic phenotype.
AB - Developing lung cancer in mouse models that display similarities of both
phenotype and genotype will undoubtedly provide further and better insights into
lung tumor biology. Moreover, a high degree of pathophysiological similarity
between lung tumors from mouse models and their human counterparts will make it
possible to use these mouse models for preclinical tests. Ovine pulmonary
adenocarcinomas (OPAs) present the same symptoms as adenocarcinomas in humans and
are caused by a betaretrovirus. OPAs have served as an exquisite model of
carcinogenesis for human lung adenocarcinomas. In this study, we characterized
the histopathology and transcriptome profiles of a jaagsiekte sheep retrovirus
(JSRV)-envelope protein (Env) transgenic mouse model with spontaneous lung
tumors, and associations of the transcriptome profiles with tumor
invasion/metastasis, especially the phenomenon of the epithelial-mesenchymal
transition (EMT). Genetic information obtained from an expression array was
analyzed using an ingenuity pathways analysis (IPA) and human disease database
(MalaCards). By careful examination, several novel EMT-related genes were
identified from tumor cells using RT-qPCR, and these genes also scored high in
MalaCards. We concluded that the JSRV-Env mouse model could serve as a
spontaneous lung adenocarcinoma model with a metastatic phenotype, which will
benefit the study of early-onset and progression of lung adenocarcinoma. In
addition, it can also be a valuable tool for biomarkers and drug screening, which
will be helpful in developing intervention therapies.
PMID- 28419108
TI - Changes in prices, sales, consumer spending, and beverage consumption one year
after a tax on sugar-sweetened beverages in Berkeley, California, US: A before
and-after study.
AB - BACKGROUND: Taxes on sugar-sweetened beverages (SSBs) meant to improve health and
raise revenue are being adopted, yet evaluation is scarce. This study examines
the association of the first penny per ounce SSB excise tax in the United States,
in Berkeley, California, with beverage prices, sales, store revenue/consumer
spending, and usual beverage intake. METHODS AND FINDINGS: Methods included
comparison of pre-taxation (before 1 January 2015) and first-year post-taxation
(1 March 2015-29 February 2016) measures of (1) beverage prices at 26 Berkeley
stores; (2) point-of-sale scanner data on 15.5 million checkouts for beverage
prices, sales, and store revenue for two supermarket chains covering three
Berkeley and six control non-Berkeley large supermarkets in adjacent cities; and
(3) a representative telephone survey (17.4% cooperation rate) of 957 adult
Berkeley residents. Key hypotheses were that (1) the tax would be passed through
to the prices of taxed beverages among the chain stores in which Berkeley
implemented the tax in 2015; (2) sales of taxed beverages would decline, and
sales of untaxed beverages would rise, in Berkeley stores more than in comparison
non-Berkeley stores; (3) consumer spending per transaction (checkout episode)
would not increase in Berkeley stores; and (4) self-reported consumption of taxed
beverages would decline. Main outcomes and measures included changes in inflation
adjusted prices (cents/ounce), beverage sales (ounces), consumers' spending
measured as store revenue (inflation-adjusted dollars per transaction) in two
large chains, and usual beverage intake (grams/day and kilocalories/day). Tax
pass-through (changes in the price after imposition of the tax) for SSBs varied
in degree and timing by store type and beverage type. Pass-through was complete
in large chain supermarkets (+1.07c/oz, p = 0.001) and small chain supermarkets
and chain gas stations (1.31c/oz, p = 0.004), partial in pharmacies (+0.45c/oz, p
= 0.03), and negative in independent corner stores and independent gas stations (
0.64c/oz, p = 0.004). Sales-unweighted mean price change from scanner data was
+0.67c/oz (p = 0.00) (sales-weighted, +0.65c/oz, p = 0.003), with +1.09c/oz (p <
0.001) for sodas and energy drinks, but a lower change in other categories. Post
tax year 1 scanner data SSB sales (ounces/transaction) in Berkeley stores
declined 9.6% (p < 0.001) compared to estimates if the tax were not in place, but
rose 6.9% (p < 0.001) for non-Berkeley stores. Sales of untaxed beverages in
Berkeley stores rose by 3.5% versus 0.5% (both p < 0.001) for non-Berkeley
stores. Overall beverage sales also rose across stores. In Berkeley, sales of
water rose by 15.6% (p < 0.001) (exceeding the decline in SSB sales in ounces);
untaxed fruit, vegetable, and tea drinks, by 4.37% (p < 0.001); and plain milk,
by 0.63% (p = 0.01). Scanner data mean store revenue/consumer spending (dollars
per transaction) fell 18c less in Berkeley (-$0.36, p < 0.001) than in comparison
stores (-$0.54, p < 0.001). Baseline and post-tax Berkeley SSB sales and usual
dietary intake were markedly low compared to national levels (at baseline,
National Health and Nutrition Examination Survey SSB intake nationally was 131
kcal/d and in Berkeley was 45 kcal/d). Reductions in self-reported mean daily SSB
intake in grams (-19.8%, p = 0.49) and in mean per capita SSB caloric intake (
13.3%, p = 0.56) from baseline to post-tax were not statistically significant.
Limitations of the study include inability to establish causal links due to
observational design, and the absence of health outcomes. Analysis of consumption
was limited by the small effect size in relation to high standard error and
Berkeley's low baseline consumption. CONCLUSIONS: One year following
implementation of the nation's first large SSB tax, prices of SSBs increased in
many, but not all, settings, SSB sales declined, and sales of untaxed beverages
(especially water) and overall study beverages rose in Berkeley; overall consumer
spending per transaction in the stores studied did not rise. Price increases for
SSBs in two distinct data sources, their timing, and the patterns of change in
taxed and untaxed beverage sales suggest that the observed changes may be
attributable to the tax. Post-tax self-reported SSB intake did not change
significantly compared to baseline. Significant declines in SSB sales, even in
this relatively affluent community, accompanied by revenue used for prevention
suggest promise for this policy. Evaluation of taxation in jurisdictions with
more typical SSB consumption, with controls, is needed to assess broader dietary
and potential health impacts.
PMID- 28419109
TI - Polymorphisms in the selectin gene cluster are associated with fertility and
survival time in a population of Holstein Friesian cows.
AB - Selectins are adhesion molecules, which mediate attachment between leucocytes and
endothelium. They aid extravasation of leucocytes from blood into inflamed tissue
during the mammary gland's response to infection. Selectins are also involved in
attachment of the conceptus to the endometrium and subsequent placental
development. Poor fertility and udder health are major causes for culling dairy
cows. The three identified bovine selectin genes SELP, SELL and SELE are located
in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in
SELP and SELE are associated with human vascular disease, while SELP SNP rs6127
has been associated with recurrent pregnancy loss in women. This study describes
the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and
SELE (n = 1) with fertility, milk production and longevity traits in a population
of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at
6 months of age and animals were monitored until either culling or 2,340 days
from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala
substitution at rs42312260. This region was associated with poor fertility and
reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus
in the linking region between consensus repeats 4 and 5, which may influence
glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy
Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA
homozygotes present in the population and AG heterozygotes had significantly
worse fertility than GG homozygotes. Small changes in milk production associated
with some SNP could not account for the reduced fertility and only SELPEx6 showed
any association with somatic cell count. These results suggest that polymorphisms
in SELP and SELE are associated with the likelihood of successful pregnancy,
potentially through compromised implantation and placental development.
PMID- 28419110
TI - Cocoa pulp in beer production: Applicability and fermentative process
performance.
AB - This work evaluated the effect of cocoa pulp as a malt adjunct on the parameters
of fermentation for beer production on a pilot scale. For this purpose, yeast
isolated from the spontaneous fermentation of cachaca (SC52), belonging to the
strain bank of the State University of Feira de Santana-Ba (Brazil), and a
commercial strain of ale yeast (Safale S-04 Belgium) were used. The beer produced
was subjected to acceptance and purchase intention tests for sensorial analysis.
At the beginning of fermentation, 30% cocoa pulp (adjunct) was added to the wort
at 12 degrees P concentration. The production of beer on a pilot scale was
carried out in a bioreactor with a 100-liter capacity, a usable volume of 60
liters, a temperature of 22 degrees C and a fermentation time of 96 hours. The
fermentation parameters evaluated were consumption of fermentable sugars and
production of ethanol, glycerol and esters. The beer produced using the adjunct
and yeast SC52 showed better fermentation performance and better acceptance
according to sensorial analysis.
PMID- 28419111
TI - Time resolved and label free monitoring of extracellular metabolites by surface
enhanced Raman spectroscopy.
AB - Metabolomics is an emerging field of cell biology that aims at the comprehensive
identification of metabolite levels in biological fluids or cells in a specific
functional state. Currently, the major tools for determining metabolite
concentrations are mass spectrometry coupled with chromatographic techniques and
nuclear magnetic resonance, which are expensive, time consuming and destructive
for the samples. Here, we report a time resolved approach to monitor metabolite
dynamics in cell cultures, based on Surface Enhanced Raman Scattering (SERS).
This method is label-free, easy to use and provides the opportunity to
simultaneously study a broad range of molecules, without the need to process the
biological samples. As proof of concept, NIH/3T3 cells were cultured in vitro,
and the extracellular medium was collected at different time points to be
analyzed with our engineered SERS substrates. By identifying individual peaks of
the Raman spectra, we showed the simultaneous detection of several components of
the conditioned medium, such as L-tyrosine, L-tryptophan, glycine, L
phenylalanine, L-histidine and fetal bovine serum proteins, as well as their
intensity changes during time. Furthermore, analyzing the whole Raman data set
with the Principal Component Analysis (PCA), we demonstrated that the Raman
spectra collected at different days of culture and clustered by similarity,
described a well-defined trajectory in the principal component plot. This
approach was then utilized to determine indirectly the functional state of the
macrophage cell line Raw 264.7, stimulated with the lipopolysaccharide (LPS) for
24 hours. The collected spectra at different time points, clustered by the PCA
analysis, followed a well-defined trajectory, corresponding to the functional
change of cells toward the activated pro-inflammatory state induced by the LPS.
This study suggests that our engineered SERS surfaces can be used as a versatile
tool both for the characterization of cell culture conditions and the functional
state of cells over time.
PMID- 28419113
TI - Evaluation of harvest and information needs for North American sea ducks.
AB - Wildlife managers routinely seek to establish sustainable limits of sport harvest
or other regulated forms of take while confronted with considerable uncertainty.
A growing body of ecological research focuses on methods to describe and account
for uncertainty in management decision-making and to prioritize research and
monitoring investments to reduce the most influential uncertainties. We used
simulation methods incorporating measures of demographic uncertainty to evaluate
risk of overharvest and prioritize information needs for North American sea ducks
(Tribe Mergini). Sea ducks are popular game birds in North America, yet they are
poorly monitored and their population dynamics are poorly understood relative to
other North American waterfowl. There have been few attempts to assess the
sustainability of harvest of North American sea ducks, and no formal harvest
strategy exists in the U.S. or Canada to guide management. The popularity of sea
duck hunting, extended hunting opportunity for some populations (i.e., special
seasons and/or bag limits), and population declines have led to concern about
potential overharvest. We used Monte Carlo simulation to contrast estimates of
allowable harvest and observed harvest and assess risk of overharvest for 7
populations of North American sea ducks: the American subspecies of common eider
(Somateria mollissima dresseri), eastern and western populations of black scoter
(Melanitta americana) and surf scoter (M. perspicillata), and continental
populations of white-winged scoter (M. fusca) and long-tailed duck (Clangula
hyemalis). We combined information from empirical studies and the opinions of
experts through formal elicitation to create probability distributions reflecting
uncertainty in the individual demographic parameters used in this assessment.
Estimates of maximum growth (rmax), and therefore of allowable harvest, were
highly uncertain for all populations. Long-tailed duck and American common eider
appeared to be at high risk of overharvest (i.e., observed harvest < allowable
harvest in 5-7% and 19-26% of simulations, respectively depending on the
functional form of density dependence), whereas the other populations appeared to
be at moderate risk to low risk (observed harvest < allowable harvest in 22-68%
of simulations, again conditional on the form of density dependence). We also
evaluated the sensitivity of the difference between allowable and observed
harvest estimates to uncertainty in individual demographic parameters to
prioritize information needs. We found that uncertainty in overall fecundity had
more influence on comparisons of allowable and observed harvest than adult
survival or observed harvest for all species except long-tailed duck. Although
adult survival was characterized by less uncertainty than individual components
of fecundity, it was identified as a high priority information need given the
sensitivity of growth rate and allowable harvest to this parameter. Uncertainty
about population size was influential in the comparison of observed and allowable
harvest for 5 of the 6 populations where it factored into the assessment. While
this assessment highlights a high degree of uncertainty in allowable harvest, it
provides a framework for integration of improved data from future research and
monitoring. It could also serve as the basis for harvest strategy development as
management objectives and regulatory alternatives are specified by the management
community.
PMID- 28419112
TI - Lens metabolomic profiling as a tool to understand cataractogenesis in Atlantic
salmon and rainbow trout reared at optimum and high temperature.
AB - Periods of high or fluctuating seawater temperatures result in several
physiological challenges for farmed salmonids, including an increased prevalence
and severity of cataracts. The aim of the present study was to compare
cataractogenesis in Atlantic salmon (Salmo salar L.) and rainbow trout
(Oncorhynchus mykiss) reared at two temperatures, and investigate whether
temperature influences lens metabolism and cataract development. Atlantic salmon
(101+/-2 g) and rainbow trout (125+/-3 g) were reared in seawater at either 13
degrees C (optimum for growth) or 19 degrees C during the 35 days experiment (n =
4 tanks for each treatment). At the end of the experiment, the prevalence of
cataracts was nearly 100% for Atlantic salmon compared to ~50% for rainbow trout,
irrespective of temperature. The severity of the cataracts, as evaluated by slit
lamp inspection of the lens, was almost three fold higher in Atlantic salmon
compared to rainbow trout. The global metabolic profile revealed differences in
lens composition and metabolism between the two species, which may explain the
observed differences in cataract susceptibility between the species. The largest
differences were seen in the metabolism of amino acids, especially the histidine
metabolism, and this was confirmed by a separate quantitative analysis. The
global metabolic profile showed temperature dependent differences in the lens
carbohydrate metabolism, osmoregulation and redox homeostasis. The results from
the present study give new insight in cataractogenesis in Atlantic salmon and
rainbow trout reared at high temperature, in addition to identifying metabolic
markers for cataract development.
PMID- 28419114
TI - H-FABP: A new biomarker to differentiate between CT-positive and CT-negative
patients with mild traumatic brain injury.
AB - The majority of patients with mild traumatic brain injury (mTBI) will have normal
Glasgow coma scale (GCS) of 15. Furthermore, only 5%-8% of them will be CT
positive for an mTBI. Having a useful biomarker would help clinicians evaluate a
patient's risk of developing intracranial lesions. The S100B protein is currently
the most studied and promising biomarker for this purpose. Heart fatty-acid
binding protein (H-FABP) has been highlighted in brain injury models and
investigated as a biomarker for stroke and severe TBI, for example. Here, we
evaluate the performances of S100B and H-FABP for differentiating between CT
positive and CT-negative patients. A total of 261 patients with a GCS score of 15
and at least one clinical symptom of mTBI were recruited at three different
European sites. Blood samples from 172 of them were collected <= 6 h after
trauma. Patients underwent a CT scan and were dichotomised into CT-positive and
CT-negative groups for statistical analyses. H-FABP and S100B levels were
measured using commercial kits, and their capacities to detect all CT-positive
scans were evaluated, with sensitivity set to 100%. For patients recruited <= 6 h
after trauma, the CT-positive group demonstrated significantly higher levels of
both H-FABP (p = 0.004) and S100B (p = 0.003) than the CT-negative group. At 100%
sensitivity, specificity reached 6% (95% CI 2.8-10.7) for S100B and 29% (95% CI
21.4-37.1) for H-FABP. Similar results were obtained when including all the
patients recruited, i.e. hospital arrival within 24 h of trauma onset. H-FABP out
performed S100B and thus seems to be an interesting protein for detecting all CT
positive mTBI patients with a GCS score of 15 and at least one clinical symptom.
PMID- 28419115
TI - Properties of the cuticular proteins of Anopheles gambiae as revealed by serial
extraction of adults.
AB - How cuticular proteins (CPs) interact with chitin and with each other in the
cuticle remains unresolved. We employed LC-MS/MS to identify CPs from 5-6 day-old
adults of Anopheles gambiae released after serial extraction with PBS, EDTA, 2-8M
urea, and SDS as well as those that remained unextracted. Results were compared
to published data on time of transcript abundance, localization of proteins
within structures and within the cuticle, as well as properties of individual
proteins, length, pI, percent histidine, tyrosine, glutamine, and number of
AAP[A/V/L] repeats. Thirteen proteins were solubilized completely, all were CPRs,
most belonging to the RR-1 group. Eleven CPs were identified in both soluble
fractions and the final pellet, including 5 from other CP families. Forty-three
were only detected from the final pellet. These included CPRs and members of the
CPAP1, CPF, CPFL, CPLCA, CPLCG, CPLCP, and TWDL families, as well as several low
complexity CPs, not assigned to families and named CPLX. For a given protein,
many histidines or tyrosines or glutamines appear to be potential participants in
cross-linking since we could not identify any peptide bearing these residues that
was consistently absent. We failed to recover peptides from the amino-terminus of
any CP. Whether this implicates that location in sclerotization or some
modification that prevents detection is not known. Soluble CPRs had lower
isoelectric points than those that remained in the final pellet; most members of
other CP families had isoelectric points of 8 or higher. Obviously, techniques
beyond analysis of differential solubility will be needed to learn how CPs
interact with each other and with chitin.
PMID- 28419116
TI - Weak experiences sufficient for creating illusory figures that influence
perception of actual lines.
AB - The question of whether conscious experience is best viewed as graded or
dichotomous has received much scientific attention in recent years as the answer
is relevant not only to models of consciousness, but also to the examination of
neural markers of consciousness in patients and infants. Although some studies
have found evidence of graded perception, it is unclear whether such perception
is simply composed of individual stimulus features perceived in an all-or-none
manner. Here, we examined whether the Kanizsa triangle (an illusory figure that
is supposedly only perceived when all its parts are visible) has an impact on
line length discrimination across four degrees of subjective visibility. We found
that the presence of the Kanizsa triangle biases line length judgments (a
phenomenon called the Ponzo illusion) when participants reported any experience
(even a weak glimpse) of the stimulus. The results support the view that
consciousness is a graded phenomenon. The strength of this support depends on the
assumption that all parts of the illusory figure must be perceived for the
illusion to work but this assumption is not resolved in the present literature.
Currently, evidence can be found both for and against this notion.
PMID- 28419117
TI - Indirect effect of temperature on fish population abundances through phenological
changes.
AB - In response to climate change, earlier phenological events have been reported for
a large range of taxa such that phenological shifts are considered as one of the
fingerprints of the effect of climate change on organisms. Evidence further
suggests that changes in the timing of phenological events might decouple biotic
interactions due to differential phenological adjustment among interacting
species, ultimately leading to population declines. Nonetheless, few studies have
investigated how climate-driven changes in the timing of phenological events
influence population abundances. In this study, we investigated how two
environmental variables known to influence the migration timing of freshwater
fish (i.e. water discharge and temperature) directly or indirectly influenced
abundances of 21 fish species using daily time series gathered at four sites
located in France over a period spanning from 9 to 21 years. We found no evidence
for long-term trends in migration timing or fish abundances over time. Using
piecewise structural equation models, we demonstrate that inter-annual variations
in abundances were driven by inter-annual variations in temperature through
variations in migration timing. Overall, our results suggest that climate change
may concomitantly influence different biological aspects (e.g. phenology,
abundance) of fish species. We argue that considering different responses to
climate change is paramount if we are to improve our understanding of how
organisms and populations are influenced by climate change in order to set-up
efficient conservation strategies.
PMID- 28419118
TI - Fatty liver disease determines the progression of coronary artery calcification
in a metabolically healthy obese population.
AB - OBJECTIVES: Metabolically healthy obese (MHO) phenotype describes an obese state
with a favorable metabolic profile. However, the prognosis of this subpopulation
remains controversial. We aimed to examine whether MHO phenotype is associated
with progression of atherosclerotic activity, reflected as the changes in
coronary artery calcification (CAC) over time. If so, we sought to determine the
role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this
progression. METHODS: We enrolled 1,240 asymptomatic subjects who underwent
repeated CAC score measurement during routine health examinations. CAC score
progression was defined as either incident CAC in a population free of CAC at
baseline, or an increase by >=2.5 units between the baseline and final square
root of CAC scores in participants with detectable CAC at baseline. Subjects were
stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state
using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography.
RESULTS: Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score
progression. The MHO phenotype was not significantly associated with CAC score
progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval
[CI], 0.93-2.25), as compared to the metabolically healthy non-obese (MHNO)
phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was
significantly associated with CAC score progression (multivariate adjusted-OR,
2.37; 95% CI, 1.34-4.16), as compared to the MHNO/no FLD phenotype, whereas the
MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71-2.24).
CONCLUSIONS: Obese individuals with FLD have an increased risk of atherosclerosis
progression, despite their healthy metabolic profile. Preventive interventions
targeting cardiometabolic risk factors should be considered in such individuals,
regardless of the weight status.
PMID- 28419119
TI - Plasma ghrelin level and plasma ghrelin/obestatin ratio are related to intestinal
metaplasia in elderly patients with functional dyspepsia.
AB - BACKGROUND: Whether plasma ghrelin/obestatin levels are associated with
Helicobacter pylori (H. pylori) infection, subtypes of functional dyspepsia (FD),
and gastric mucosal histology has not yet been established in elderly patients.
OBJECTIVE: The aim of this study was to determine whether plasma ghrelin and
obestatin levels are related to gastric mucosal histology, H. pylori infection,
and FD subtypes in elderly patients with FD. METHODS: Ninety-two patients
diagnosed with FD and older than 60 years (median age 69.4; range 60-88) were
included. Clinical symptoms investigated included postprandial fullness,
epigastric pain, epigastric soreness, nausea, and vomiting. According to the Rome
III criteria, patients diagnosed with FD were divided into two subtypes:
epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Plasma
ghrelin and obestatin levels were measured using enzyme immunoassay, and
histological examination of gastric mucosa was performed. H. pylori infection was
determined by histopathological examination of gastric mucosal biopsy and/or
Campylobacter-like organism test. RESULTS: In our study, plasma ghrelin levels
and plasma ghrelin/obestatin (G/O) ratio were significantly lower in subjects
with intestinal metaplasia compared with those without intestinal metaplasia
(ghrelin, p = 0.010; G/O ratio, p = 0.012). On the other hand, there were no
significant differences in plasma ghrelin and obestatin levels between H. pylori
positive and H. pylori-negative groups. (ghrelin, p = 0.130; obestatin, p =
0.888). Similarly, no significant differences were detected between the EPS and
PDS groups (ghrelin, p = 0.238; obestatin, p = 0.710). CONCLUSIONS: Patients with
intestinal metaplasia, a known precursor of gastric cancer, had significantly
less plasma ghrelin levels and G/O ratio than those without intestinal
metaplasia.
PMID- 28419120
TI - Structural and functional changes in the microcirculation of lepromatous leprosy
patients - Observation using orthogonal polarization spectral imaging and laser
Doppler flowmetry iontophoresis.
AB - Leprosy is a chronic granulomatous infection of skin and peripheral nerves caused
by Mycobacterium leprae and is considered the main infectious cause of disability
worldwide. Despite the several studies regarding leprosy, little is known about
its effects on microvascular structure and function in vivo. Thus, we have aimed
to compare skin capillary structure and functional density, cutaneous vasomotion
(spontaneous oscillations of arteriolar diameter), which ensures optimal blood
flow distribution to skin capillaries) and cutaneous microvascular blood flow and
reactivity between ten men with lepromatous leprosy (without any other
comorbidity) and ten age- and gender-matched healthy controls. Orthogonal
polarization spectral imaging was used to evaluate skin capillary morphology and
functional density and laser Doppler flowmetry to evaluate blood flow, vasomotion
and spectral analysis of flowmotion (oscillations of blood flow generated by
vasomotion) and microvascular reactivity, in response to iontophoresis of
acetylcholine and sodium nitroprusside. The contribution of different frequency
components of flowmotion (endothelial, neurogenic, myogenic, respiratory and
cardiac) was not statistically different between groups. However, endothelial
dependent and -independent vasodilatations elicited by acetylcholine and sodium
nitroprusside iontophoresis, respectively, were significantly reduced in
lepromatous leprosy patients compared to controls, characterizing the existence
of microvascular dysfunction. These patients also presented a significant
increase in the number of capillaries with morphological abnormalities and in the
diameters of the dermal papilla and capillary bulk when compared to controls. Our
results suggest that lepromatous leprosy causes severe microvascular dysfunction
and significant alterations in capillary structure. These structural and
functional changes are probably induced by exposure of the microvascular bed to
chronic inflammation evoked by the Mycobacterium leprae.
PMID- 28419121
TI - The magnitude of ivacaftor effects on fluid secretion via R117H-CFTR channels:
Human in vivo measurements.
AB - We optically measured effects of orally available ivacaftor (Kalydeco(r)) on
sweat rates of identified glands in 3 R117H subjects, each having a unique set of
additional mutations, and compared them with 5 healthy control subjects tested
contemporaneously. We injected beta-adrenergic agonists intradermally to
stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which
persists in CF subjects. We focused on an R117H-7T/F508del subject who produced
quantifiable C-sweat off ivacaftor and was available for 1 blinded, 3 off
ivacaftor, and 3 on ivacaftor tests, allowing us to estimate in vivo fold
increase in sweat rates produced by ivacaftor's effect on the open probability
(PO) of R117H-CFTR. Measured sweat rates must be corrected for sweat losses. With
estimated sweat losses of 0.023 to 0.08 nl.gland-1.min-1, ivacaftor increased the
average C-sweat rates 3-7 fold, and estimated function as % of WT were 4.1-12%
off ivacaftor and 21.9-32% on ivacaftor (larger values reflect increased loss
estimates). Based on single tests, an R117H-7T/ R117H-7T subject showed 6-9% WT
function off ivacaftor and 28-43% on ivacaftor. Repeat testing of an R117H
5T/F508del subject detected only trace responding to ivacaftor. We conclude that
in vivo, R117H PO is strongly increased by ivacaftor, but channel number, mainly
determined by variable deletion of exon 10, has a marked influence on outcomes.
PMID- 28419122
TI - Lauric acid as feed additive - An approach to reducing Campylobacter spp. in
broiler meat.
AB - The increasing prevalence of Campylobacter spp. within broiler populations is a
major problem for food safety and consumer protection worldwide. In vitro studies
could already demonstrate that Campylobacter spp. are susceptible to lauric acid.
The purpose of this study was to examine in vivo the influence of lauric acid as
a feed additive on slaughter parameters, muscle fatty acid profile, meat quality
traits and the reduction of Campylobacter coli in inoculated meat of Ross 308
(R308) and Hubbard JA 757 (HJA) broilers in three independent trials (n = 3).
Although slaughter parameters did not show any significant differences, the fatty
acid profile of both breeds revealed significantly higher lauric acid
concentrations (P < 0.0001) in the Musculus pectoralis superficialis of treated
broilers. Comparing both tested breeds, R308 test broilers had significantly
higher lauric acid concentrations than HJA test broilers (P < 0.0001), indicating
a higher conversion rate in those animals. The meat quality traits showed no
differences in the R308 breed (P > 0.05), but HJA test broilers had higher values
for drip loss, electrical conductivity, CIE color values L* and b*, and lower pH
values. The inoculation trials of R308 showed that initial bacterial loads of 5.9
log10 cfu/g were reduced during six days of storage (4 degrees C) to
approximately 4.3 log10 cfu/g in the control groups compared to 3.5 log10 cfu/g
in the treatment groups (P = 0.0295), which could be due to antimicrobial effects
of lauric acid within the muscle. This study therefore suggests that lauric acid
as a feed additive has the potential to improve food safety by reducing the
numbers of Campylobacter coli in broiler meat. However, this effect seems to be
dependent on the breed determining the feed intake capacity, the fat deposition
and therefore the ability to incorporate lauric acid in the muscle.
PMID- 28419123
TI - Low-resistive vibratory penetration in granular media.
AB - Non-cohesive materials such as sand, dry snow or cereals are encountered in
various common circumstances, from everyday situations to industry. The process
of digging into these materials remains a challenge to most animals and machines.
Within the animal kingdom, different strategies are employed to overcome this
issue, including excavation methods used by ants, the two-anchor strategy
employed by soft burrowers such as razor-clams, and undulatory motions exhibited
by sandfish lizards. Despite the development of technology to mimic these
techniques in diggers and robots, the limitations of animals and machines may
differ, and mimicry of natural processes is not necessarily the most efficient
technological strategy. This study presents evidence that the resisting force for
the penetration of an intruder into a dry granular media can be reduced by one
order of magnitude with small amplitude (A ? 10 MUm) and low frequency (f = 50 -
200 Hz) mechanical vibrations. This observed result is attributed to the local
fluidization of the granular bed which induces the rupture of force chains. The
drop in resistive force on entering dry granular materials may be relevant in
technological development in order to increase the efficiency of diggers and
robots.
PMID- 28419124
TI - A randomised controlled trial of losartan as an anti-fibrotic agent in non
alcoholic steatohepatitis.
AB - INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease
worldwide. Experimental and small clinical trials have demonstrated that
angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this
randomised controlled trial was to assess whether treatment with Losartan for 96
weeks slowed, halted or reversed the progression of fibrosis in patients with non
alcoholic steatohepatitis (NASH). METHODS: Double-blind randomised-controlled
trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with
histological evidence of NASH. The primary outcome for the study was change in
histological fibrosis stage from pre-treatment to end-of-treatment. RESULTS: The
study planned to recruit 214 patients. However, recruitment was slower than
expected, and after 45 patients were randomised (median age 55; 56% male; 60%
diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients
(15 losartan and 17 placebo) completed follow up period: one patient (6.7%)
treated with losartan and 4 patients (23.5%) in the placebo group were
"responders" (lower fibrosis stage at follow up compared with baseline). The
major reason for slow recruitment was that 39% of potentially eligible patients
were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and
15% were taking other prohibited medications. CONCLUSIONS: Due to the widespread
use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient
patients to determine whether losartan has anti-fibrotic effects in the liver.
TRIAL REGISTRATION: ISRCTN 57849521.
PMID- 28419125
TI - Mammographic compression in Asian women.
AB - OBJECTIVES: To investigate: (1) the variability of mammographic compression
parameters amongst Asian women; and (2) the effects of reducing compression force
on image quality and mean glandular dose (MGD) in Asian women based on phantom
study. METHODS: We retrospectively collected 15818 raw digital mammograms from
3772 Asian women aged 35-80 years who underwent screening or diagnostic
mammography between Jan 2012 and Dec 2014 at our center. The mammograms were
processed using a volumetric breast density (VBD) measurement software (Volpara)
to assess compression force, compression pressure, compressed breast thickness
(CBT), breast volume, VBD and MGD against breast contact area. The effects of
reducing compression force on image quality and MGD were also evaluated based on
measurement obtained from 105 Asian women, as well as using the RMI156
Mammographic Accreditation Phantom and polymethyl methacrylate (PMMA) slabs.
RESULTS: Compression force, compression pressure, CBT, breast volume, VBD and MGD
correlated significantly with breast contact area (p<0.0001). Compression
parameters including compression force, compression pressure, CBT and breast
contact area were widely variable between [relative standard deviation
(RSD)>=21.0%] and within (p<0.0001) Asian women. The median compression force
should be about 8.1 daN compared to the current 12.0 daN. Decreasing compression
force from 12.0 daN to 9.0 daN increased CBT by 3.3+/-1.4 mm, MGD by 6.2-11.0%,
and caused no significant effects on image quality (p>0.05). CONCLUSIONS: Force
standardized protocol led to widely variable compression parameters in Asian
women. Based on phantom study, it is feasible to reduce compression force up to
32.5% with minimal effects on image quality and MGD.
PMID- 28419126
TI - Availability and affordability of antimalarial and antibiotic medicines in
Malawi.
AB - BACKGROUND: Availability and affordability of medicines are key determinants of
universal health coverage, yet achieving them presents a major challenge
especially in low-income countries. We here present an analysis of availability
and prices of antimalarial and antibiotic medicines in public, faith-based and
private health facilities in Malawi. Medicines are provided free of charge in the
public health care system of Malawi. In contrast, facilities of the Christian
Health Association of Malawi (CHAM) usually charge their patients for medicines,
as do private for-profit facilities. METHODS: As part of a study on medicine
quality, samples of six antimalarial and six antibiotic medicines were collected
in 31 health facilities in four districts of southern Malawi. These included 15
public facilities (i.e. health centres, district hospitals and central
hospitals), eight CHAM and eight private facilities. Random selection was used in
choosing the included health facilities. The availability of medicines was
recorded, including the number of units which could be collected of each
medicine, as well as the prices of medicines which were charged in CHAM and
private facilities. These data were analyzed using the standard methodology
developed by the World Health Organization (WHO) and Health Action International
(HAI). RESULTS: Availability of the antimalarials artemether/lumefantrine and
sulfadoxine/pyrimethamine, which are provided with financial support from
international donors, was high in public and CHAM facilities (93% and 100%,
respectively). However, availability of antibiotics was much lower (e.g. 40%
availability of amoxicillin tablets/capsules in public health centres). Medicine
prices were lower than reported from many other countries. The median price ratio
(MPR) to a wholesale international procurement price was 2.8 in CHAM facilities
and even lower in the private sector (MPR 2.3). Nevertheless, for 10 of the 12
investigated medicines the cost for one course of treatment exceeded the daily
wage of a low-paid government worker in Malawi and therefore had to be considered
as unaffordable for a major part of the population. CONCLUSIONS: Continued
efforts are required to improve the availability of essential medicines in
Malawi. The free provision of medicines in the public health care system remains
important in order to achieve universal health coverage, due to the low income in
this country.
PMID- 28419127
TI - Effects of nitrogen application rate, nitrogen synergist and biochar on nitrous
oxide emissions from vegetable field in south China.
AB - Globally, vegetable fields are the primary source of greenhouse gas emissions. A
closed-chamber method together with gas chromatography was used to measure the
fluxes of nitrous oxide (N2O) emissions in typical vegetable fields planted with
four vegetables sequentially over time in the same field: endive, lettuce,
cabbage and sweet corn. Results showed that N2O fluxes occurred in pulses with
the N2O emission peak varying greatly among the crops. In addition, N2O emissions
were linearly associated with the nitrogen (N) application rate (r = 0.8878, n =
16). Excessive fertilizer N application resulted in N loss through nitrous oxide
gas emitted from the vegetable fields. Compared with a conventional fertilization
(N2) treatment, the cumulative N2O emissions decreased significantly in the
growing seasons of four plant species from an nitrogen synergist (a nitrification
inhibitor, dicyandiamide and biochar treatments by 34.6% and 40.8%, respectively.
However, the effects of biochar on reducing N2O emissions became more obvious
than that of dicyandiamide over time. The yield-scaled N2O emissions in
consecutive growing seasons for four species increased with an increase in the N
fertilizer application rate, and with continuous application of N fertilizer.
This was especially true for the high N fertilizer treatment that resulted in a
risk of yield-scaled N2O emissions. Generally, the additions of dicyandiamide and
biochar significantly decreased yield-scaled N2O-N emissions by an average of
45.9% and 45.7%, respectively, compared with N2 treatment from the consecutive
four vegetable seasons. The results demonstrated that the addition of
dicyandiamide or biochar in combination with application of a rational amount of
N could provide the best strategy for the reduction of greenhouse gas emissions
in vegetable field in south China.
PMID- 28419128
TI - Cytoskeletal stability and metabolic alterations in primary human macrophages in
long-term microgravity.
AB - The immune system is one of the most affected systems of the human body during
space flight. The cells of the immune system are exceptionally sensitive to
microgravity. Thus, serious concerns arise, whether space flight associated
weakening of the immune system ultimately precludes the expansion of human
presence beyond the Earth's orbit. For human space flight, it is an urgent need
to understand the cellular and molecular mechanisms by which altered gravity
influences and changes the functions of immune cells. The CELLBOX-PRIME (=
CellBox-Primary Human Macrophages in Microgravity Environment) experiment
investigated for the first time microgravity-associated long-term alterations in
primary human macrophages, one of the most important effector cells of the immune
system. The experiment was conducted in the U.S. National Laboratory on board of
the International Space Station ISS using the NanoRacks laboratory and Biorack
type I standard CELLBOX EUE type IV containers. Upload and download were
performed with the SpaceX CRS-3 and the Dragon spaceship on April 18th, 2014 /
May 18th, 2014. Surprisingly, primary human macrophages exhibited neither
quantitative nor structural changes of the actin and vimentin cytoskeleton after
11 days in microgravity when compared to 1g controls. Neither CD18 or CD14
surface expression were altered in microgravity, however ICAM-1 expression was
reduced. The analysis of 74 metabolites in the cell culture supernatant by GC-TOF
MS, revealed eight metabolites with significantly different quantities when
compared to 1g controls. In particular, the significant increase of free fucose
in the cell culture supernatant was associated with a significant decrease of
cell surface-bound fucose. The reduced ICAM-1 expression and the loss of cell
surface-bound fucose may contribute to functional impairments, e.g. the
activation of T cells, migration and activation of the innate immune response. We
assume that the surprisingly small and non-significant cytoskeletal alterations
represent a stable "steady state" after adaptive processes are initiated in the
new microgravity environment. Due to the utmost importance of the human
macrophage system for the elimination of pathogens and the clearance of apoptotic
cells, its apparent robustness to a low gravity environment is crucial for human
health and performance during long-term space missions.
PMID- 28419129
TI - Factors related to axial length elongation and myopia progression in
orthokeratology practice.
AB - PURPOSE: To investigate which baseline factors are predictive for axial length
growth over an average period of 2.5 years in a group of children wearing
orthokeratology (OK) contact lenses. METHODS: In this retrospective study, the
clinical records of 249 new OK wearers between January 2012 and December 2013
from the contact lens clinic at the Eye and ENT Hospital of Fudan University were
reviewed. The primary outcome measure was axial length change from baseline to
the time of review (July-August 2015). Independent variables included baseline
measures of age at initiation of OK wear, gender, refractive error (spherical
equivalent), astigmatism, average keratometry, corneal toricity, central corneal
thickness, white-to-white corneal diameter, pupil size, corneal topography
eccentricity value (e-value), intraocular pressure (IOP) and total time in follow
up (months total). The contributions of all independent variables on axial length
change at the time of review were assessed using univariate and multivariable
regression analyses. RESULTS: Univariate analyses of the right eyes of 249 OK
patients showed that smaller increases in axial length were associated with older
age at the onset of OK lens wear, greater baseline spherical equivalent myopic
refractive error, less time in follow-up and a smaller e-value. Multivariable
analyses of the significant right eye variables showed that the factors
associated with smaller axial length growth were older age at the onset of OK
lens wear (p<0.0001), greater baseline spherical equivalent myopic refractive
error (p = 0.0046) and less time in follow-up (p<0.0001). CONCLUSIONS: The
baseline factors demonstrating the greatest correlation with reduced axial length
elongation during OK lens wear in myopic children included greater baseline
spherical equivalent myopic refractive error and older age at the onset of OK
lens wear.
PMID- 28419130
TI - Virus-induced down-regulation of GmERA1A and GmERA1B genes enhances the stomatal
response to abscisic acid and drought resistance in soybean.
AB - Drought is a major threat to global soybean production. The limited
transformation potential and polyploid nature of soybean have hindered functional
analysis of soybean genes. Previous research has implicated farnesylation in the
plant's response to abscisic acid (ABA) and drought tolerance. We therefore used
virus-induced gene silencing (VIGS) to evaluate farnesyltransferase genes,
GmERA1A and GmERA1B (Glycine max Enhanced Response to ABA1-A and -B), as
potential targets for increasing drought resistance in soybean. Apple latent
spherical virus (ALSV)-mediated GmERA1-down-regulated soybean leaves displayed an
enhanced stomatal response to ABA and reduced water loss and wilting under
dehydration conditions, suggesting that GmERA1A and GmERA1B negatively regulate
ABA signaling in soybean guard cells. The findings provide evidence that the ALSV
VIGS system, which bypasses the need to generate transgenic plants, is a useful
tool for analyzing gene function using only a single down-regulated leaf. Thus,
the ALSV-VIGS system could constitute part of a next-generation molecular
breeding pipeline to accelerate drought resistance breeding in soybean.
PMID- 28419131
TI - Aflatoxin levels in sunflower seeds and cakes collected from micro- and small
scale sunflower oil processors in Tanzania.
AB - Aflatoxin, a mycotoxin found commonly in maize and peanuts worldwide, is
associated with liver cancer, acute toxicosis, and growth impairment in humans
and animals. In Tanzania, sunflower seeds are a source of snacks, cooking oil,
and animal feed. These seeds are a potential source of aflatoxin contamination.
However, reports on aflatoxin contamination in sunflower seeds and cakes are
scarce. The objective of the current study was to determine total aflatoxin
concentrations in sunflower seeds and cakes from small-scale oil processors
across Tanzania. Samples of sunflower seeds (n = 90) and cakes (n = 92) were
collected across two years, and analyzed for total aflatoxin concentrations using
a direct competitive enzyme-linked immunosorbent assay (ELISA). For seed samples
collected June-August 2014, the highest aflatoxin concentrations were from Dodoma
(1.7-280.6 ng/g), Singida (1.4-261.8 ng/g), and Babati-Manyara (1.8-162.0 ng/g).
The highest concentrations for cakes were from Mbeya (2.8-97.7 ng/g), Dodoma (1.9
88.2 ng/g), and Singida (2.0-34.3 ng/g). For seed samples collected August
October 2015, the highest concentrations were from Morogoro (2.8-662.7 ng/g),
Singida (1.6-217.6 ng/g) and Mbeya (1.4-174.2 ng/g). The highest concentrations
for cakes were from Morogoro (2.7-536.0 ng/g), Dodoma (1.4-598.4 ng/g) and
Singida (3.2-52.8 ng/g). In summary, humans and animals are potentially at high
risk of exposure to aflatoxins through sunflower seeds and cakes from micro-scale
millers in Tanzania; and location influences risk.
PMID- 28419132
TI - Spectrophotometric and molecular modelling studies on in vitro interaction of
tyrosine kinase inhibitor linifanib with bovine serum albumin.
AB - Linifanib (LNF) possess antitumor activity and acts by inhibiting receptor
tyrosine kinase VEGF and PDGF. The interaction of BSA with the drug can provide
valuable information regarding the pharmacokinetic and pharmacodynamics behavior
of drug. In our study the spectrophotometric methods and molecular docking
studies were executed to understand the interaction behavior of BSA and LNF. BSA
has an intrinsic fluorescence and that fluorescence was quenched by LNF. This
quenching process was studied at three different temperatures of 288, 300and 308
K. The interaction between LNF and BSA was due to static quenching because the
Ksv (Stern-Volmer constant) at 288 K was higher than at 300 and 308 K. Kq
(quenching rate constant) behaved in a similar fashion as the Ksv. Several other
parameters like binding constants, number of binding sites and binding energy in
addition to molecular docking studies were also used to evaluate the interaction
process. A decrease in the binding constants was observed with increasing
temperatures and the binding site number approximated unity. The decreasing
binding constant indicates LNF-BSA complex stability. The site mark competition
experiment confirmed the binding site for LNF was located on site II of BSA. UV
visible studies along with synchronous fluorescence confirm a small change in the
conformation of BSA upon interaction with LNF. The thermodynamic analysis
provided the values for free energy DeltaG0, DeltaH0 and DeltaS0. The DeltaG0 at
the 288, 300 and 308 K ranged in between -21.5 to -23.3 kJ mol-1, whereas the
calculated values of DeltaH (-55.91 kJ mol-1) and DeltaS0 (-111.74 J mol-1.K-1).
The experimental and molecular docking results suggest that the interaction
between LNF and BSA was spontaneous and they exhibited hydrogen bonding and van
der Waals force between them.
PMID- 28419133
TI - Reproductive toxicity after levetiracetam administration in male rats: Evidence
for role of hormonal status and oxidative stress.
AB - Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of
epilepsy because of its excellent safety profile in all age groups. It is
remarkable that there are no studies evaluating the toxic effects of this drug on
the male reproductive system, as it is commonly used in male patients of
reproductive age. From this point of view, our aim was to evaluate the possible
toxic effects of LEV on the male reproductive system. Therefore, LEV was
administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive
days. At the end of this period, alterations to body and organ weights were
calculated, and sperm concentration, motility, and morphology were investigated
by a computer-assisted sperm analysis system. Sperm DNA damage was determined by
comet assay and histopathological examination of the testes was carried out.
Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone
(LH) levels were measured by ELISAs to determine the effects of hormonal status,
while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in
the testes were measured by colorimetric assay kits to determine the role of
oxidative status in potential toxicity. According to the results, sperm quality
was decreased by LEV treatment in a dose-dependent manner. LEV induced
significant DNA damage in the 150 and 300 mg/kg LEV-administered groups.
Histopathology of the testes showed that LEV resulted in testicular injury in the
300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were
significantly decreased in the 300 mg/kg LEV-administered group. Glutathione,
superoxide dismutase, and catalase levels were significantly decreased in all
experimental groups while malondialdehyde levels were significantly increased in
150 and 300 mg/kg LEV-administered groups. According to these results, it was
determined that LEV administration decreased sperm quality and it was alleged
that hormonal alteration and oxidative stress are potential contributors to
reproductive toxicity.
PMID- 28419134
TI - Development of mismatch amplification mutation assays for the differentiation of
MS1 vaccine strain from wild-type Mycoplasma synoviae and MS-H vaccine strains.
AB - Mycoplasma synoviae is an economically significant pathogen in the poultry
industry, inducing respiratory disease and infectious synovitis in chickens and
turkeys, and eggshell apex abnormality in chickens. Eradication, medication and
vaccination are the options for controlling M. synoviae infection. Currently
there are two commercial, live, attenuated vaccines available against M.
synoviae: the temperature sensitive MS-H vaccine strain and the NAD independent
MS1 vaccine strain. Differentiation of vaccine strains from field isolates is
essential during vaccination and eradication programs. The present study provides
melt-curve and agarose gel based mismatch amplification mutation assays (MAMA) to
discriminate the MS1 vaccine strain from the MS-H vaccine strain and wild-type M.
synoviae isolates. The assays are based on the A/C single nucleotide polymorphism
at nt11 of a HIT family protein coding gene. The melt- and agarose-MAMAs reliably
distinguish the MS1 vaccine strain genotype from the MS-H vaccine strain and wild
type M. synoviae isolate genotype from 102 template number/DNA sample. No cross
reactions with other avian Mycoplasma species were observed. The assays can be
performed directly on clinical samples and they can be run simultaneously with
the previously described MAMAs designed for the discrimination of the MS-H
vaccine strain. The developed assays are applicable in laboratories with limited
facilities and promote the rapid, simple and cost effective differentiation of
the MS1 vaccine strain.
PMID- 28419135
TI - An organotypic slice culture to study the formation of calyx of Held synapses in
vitro.
AB - The calyx of Held, a large axo-somatic relay synapse containing hundreds of
presynaptic active zones, is possibly the largest nerve terminal in the mammalian
CNS. Studying its initial growth in-vitro might provide insights into the
specification of synaptic connection size in the developing brain. However,
attempts to maintain calyces of Held in organotypic cultures have not been
fruitful in past studies. Here, we describe an organotypic slice culture method
in which calyces of Held form in-vitro. We made coronal brainstem slices with an
optimized slice angle using newborn mice in which calyces have not yet formed;
the presynaptic bushy cells were genetically labeled using the Math5 promoter.
After six to nine days of culturing, we readily observed large Math5-positive
nerve terminals in the medial nucleus of the trapezoid body (MNTB), but not in
the neighboring lateral superior olive nucleus (LSO). These calyx-like synapses
expressed the Ca2+- sensor Synaptotagmin-2 (Syt-2) and the Ca2+ binding protein
Parvalbumin (PV), two markers of developing calyces of Held in vivo. Application
of the BMP inhibitor LDN-193189 significantly inhibited the growth of calyx
synapses, demonstrating the feasibility of long-term pharmacological manipulation
using this organotypic culture method. These experiments provide a method for
organotypic culturing of calyces of Held, and show that the formation of calyx
like synapses onto MNTB neurons can be preserved in-vitro. Furthermore, our study
adds pharmacological evidence for a role of BMP-signaling in the formation of
large calyx of Held synapses.
PMID- 28419136
TI - Occurrence of Leishmania infantum in the central nervous system of naturally
infected dogs: Parasite load, viability, co-infections and histological
alterations.
AB - Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum
and little is known about the occurrence and pathogenesis of this parasite in the
CNS. The aims of this study were to evaluate the occurrence, viability and load
of L. infantum in the CNS, and to identify the neurological histological
alterations associated with this protozoan and its co-infections in naturally
infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum
was isolated after necropsy were examined. Cerebrospinal fluid (CSF) samples were
analyzed by parasitological culture, quantitative real-time PCR (qPCR) and the
rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and
spleen samples were submitted to parasitological culture, qPCR, and histological
techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis
antibodies in serum and distemper virus antigens in CSF were investigated. None
of the dogs showed neurological signs. All dogs tested positive for L. infantum
in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal
cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61%
of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31%
of the animals; of these, 66% were seropositive for E. canis and/or T. gondii.
Amastigote forms were associated with granulomatous non-suppurative
encephalomyelitis in a dog without evidence of co-infections. The highest
frequency of L. infantum DNA was observed in the brain (98%), followed by the
spinal cord (96%), spleen (95%), and CSF (50%). The highest L. infantum load in
CNS was found in the spinal cord. These results demonstrate that L. infantum can
cross the blood-brain barrier, spread through CSF, and cause active infection in
the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the
CNS that can lead to neurological signs with progression of the disease.
PMID- 28419137
TI - Transcriptional changes in litchi (Litchi chinensis Sonn.) inflorescences treated
with uniconazole.
AB - In Arabidopsis, treating shoots with uniconazole can result in enhanced primary
root elongation and bolting delay. Uniconazole spraying has become an important
cultivation technique in controlling the flowering and improving the fruit
setting of litchi. However, the mechanism by which uniconazole regulates the
complicated developmental processes in litchi remains unclear. This study aimed
to determine which signal pathways and genes drive the responses of litchi
inflorescences to uniconazole treatment. We monitored the transcriptional
activity in inflorescences after uniconazole treatment by Illumina sequencing
technology. The global expression profiles of uniconazole-treated litchi
inflorescences were compared with those of the control, and 4051 differentially
expressed genes were isolated. KEGG pathway enrichment analysis indicated that
the plant hormone signal transduction pathway served key functions in the flower
developmental stage under uniconazole treatment. Basing on the transcriptional
analysis of genes involved in flower development, we hypothesized that
uniconazole treatment increases the ratio of female flowers by activating the
transcription of pistil-related genes. This phenomenon increases opportunities
for pollination and fertilization, thereby enhancing the fruit-bearing rate. In
addition, uniconazole treatment regulates the expression of unigenes involved in
numerous transcription factor families, especially the bHLH and WRKY families.
These findings suggest that the uniconazole-induced morphological changes in
litchi inflorescences are related to the control of hormone signaling, the
regulation of flowering genes, and the expression levels of various transcription
factors. This study provides comprehensive inflorescence transcriptome data to
elucidate the molecular mechanisms underlying the response of litchi flowers to
uniconazole treatment and enumerates possible candidate genes that can be used to
guide future research in controlling litchi flowering.
PMID- 28419138
TI - Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with
scrub typhus.
AB - BACKGROUND: The aim of this study is to investigate the clinical significance of
neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1
(KIM-1) for acute kidney injury (AKI) in patients with scrub typhus. METHODS:
From 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we
enrolled 138 patients who were followed up until renal recovery or for at least 3
months. We measured serum and urine NGAL and KIM-1 levels and evaluated
prognostic factors affecting scrub typhus-associated AKI. RESULTS: Of the 138
patients, 25 had scrub typhus-associated AKI. The incidence of AKI was 18.1%; of
which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure,
respectively, according to RIFLE criteria. Compared with patients in the non-AKI
group, patients in the AKI group were older and showed higher total leukocyte
counts and hypoalbuminemia or one or more comorbidities such as hypertension (72%
vs 33%, p<0.01), diabetes (40% vs 14%, p<0.01), or chronic kidney disease (32% vs
1%, p<0.01). In addition, serum NGAL values (404+/- 269 vs 116+/- 78 ng/mL,
P<0.001), KIM-1 values (0.80+/- 0.52 vs 0.33+/- 0.68 ng/mL, P<0.001), urine
NGAL/creatinine values (371+/- 672 vs 27+/- 39 ng/mg, P<0.001) and urine KIM
1/creatinine values (4.04+/- 2.43 vs 2.38+/- 1.89 ng/mg, P<0.001) were higher in
the AKI group than in the non-AKI group. By multivariate logistic regression,
serum NGAL and the presence of chronic kidney disease were significant predictors
of AKI. CONCLUSION: Serum NGAL might be an additive predictor for scrub typhus
associated AKI.
PMID- 28419139
TI - Skeletal-related events and mortality among men diagnosed with advanced prostate
cancer: The impact of alternative measures of radiation to the bone.
AB - PURPOSE/OBJECTIVE(S): Skeletal-related events (SREs), which include radiation to
the bone (RtB), can occur among patients with bone metastasis (BM). There is a
recognized potential for misclassification of RtB when using claims data. We
compared alternative measures of RtB to better understand their impact on SRE
prevalence and SRE-related mortality. METHODS AND MATERIALS: We analyzed data for
stage IV prostate cancer (PCa) cases identified between 2005 and 2009 in the
Surveillance, Epidemiology, and End Results registry linked with Medicare claims.
We created two measures of RtB: 1) a literature-based measure requiring the
presence of a prior claim with a BM code; 2) a new measure requiring either that
the BM code coincided with the radiation episode or that the duration of the
radiation episode was less than or equal to 4 weeks. We estimated adjusted hazard
ratios of an SRE using both measures among stratified samples: no metastasis
(M0), metastasis to bone (M1b) and other sites (M1c). RESULTS: The study sample
included 5,074 men with stage IV PCa (median age 77 years), of whom 22% had M0,
54% had M1b, and 24% had M1c disease at time of PCa diagnosis. Based on
Approaches 1 and 2, the proportion with probable RtB was 5% and 8% among M0, 30%
and 30% among M1b, and 25% and 27% among M1c patients. Among M0 patients, the
adjusted hazard ratio (AHR) associated with an SRE was 1.27 when using Approach 1
(95% confidence interval, CI: 0.95-1.7) and 1.49 when using Approach 2 (95% CI:
1.14-1.96). However, the impact of SREs on mortality did not differ between both
approaches among M1b and M1c patients. CONCLUSION: We found that alternative
measures used to define RtB as SRE in claims data impact conclusions regarding
the effect of SREs on mortality among M0 but not M1 patients.
PMID- 28419141
TI - Ghrelin is a prognostic marker and a potential therapeutic target in breast
cancer.
AB - Ghrelin and obestatin are gastrointestinal peptides, encoded by the same
preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has
been implicated in breast cancer tumorigenesis. Despite recent advances in breast
cancer management the need for new prognostic markers and potential therapeutic
targets in breast cancer remains high. We studied the prognostic impact of
ghrelin and obestatin in women with node negative breast cancer. Within a cohort
of women with breast cancer with tumor size <= 50 mm, no lymph node metastases
and no initiation of adjuvant chemotherapy, 190 women were identified who died
from breast cancer and randomly selected 190 women alive at the corresponding
time as controls. Tumor tissues were immunostained with antibodies versus the
peptides. Ghrelin expression was associated with better breast cancer specific
survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate
models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89).
Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin
expression is independent prognostic factor for breast cancer death in node
negative patients-halving the risk for dying of breast cancer. Our data implies
that ghrelin could be a potential therapeutic target in breast cancer treatment.
PMID- 28419140
TI - Niche matters: The comparison between bone marrow stem cells and endometrial stem
cells and stromal fibroblasts reveal distinct migration and cytokine profiles in
response to inflammatory stimulus.
AB - OBJECTIVE: Intrinsic inflammatory characteristics play a pivotal role in stem
cell recruitment and homing through migration where the subsequent change in
niche has been shown to alter these characteristics. The bone marrow mesenchymal
stem cells (bmMSCs) have been demonstrated to migrate to the endometrium
contributing to the stem cell reservoir and regeneration of endometrial tissue.
Thus, the aim of the present study was to compare the inflammation-driven
migration and cytokine secretion profile of human bmMSCs to endometrial
mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs). MATERIALS AND
METHODS: The bmMSCs were isolated from bone marrow aspirates through culturing,
whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their
surface marker, proliferation profiles and migration properties towards serum and
inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets
was analysed in each cell type at basal level along with lipopolysaccharide (LPS)
induced state. RESULTS: Both stem cell types, bmMSCs and eMSCs, presented with
similar stem cell surface marker profiles as well as possessed high proliferation
and migration potential compared to eSFs. In multiplex assays, the secretion of
16 cytokine targets was detected and LPS stimulation expanded the cytokine
secretion pattern by triggering the secretion of several targets. The bmMSCs
exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF)
A, stromal cell-derived factor-1 alpha (SDF)-1alpha, interleukin-1 receptor
antagonist (IL-1RA), IL-6, interferon-gamma inducible protein (IP)-10, monocyte
chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)1alpha and
RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8
secretion was higher in both endometrial cell types compared to bmMSCs.
CONCLUSION: Our results highlight that similar to bmMSCs, the eMSCs possess high
migration activity while the differentiation process towards stromal fibroblasts
seemed to result in loss of stem cell surface markers, minimal migration activity
and a subtler cytokine profile likely contributing to normal endometrial
function.
PMID- 28419142
TI - Multispot single-molecule FRET: High-throughput analysis of freely diffusing
molecules.
AB - We describe an 8-spot confocal setup for high-throughput smFRET assays and
illustrate its performance with two characteristic experiments. First,
measurements on a series of freely diffusing doubly-labeled dsDNA samples allow
us to demonstrate that data acquired in multiple spots in parallel can be
properly corrected and result in measured sample characteristics consistent with
those obtained with a standard single-spot setup. We then take advantage of the
higher throughput provided by parallel acquisition to address an outstanding
question about the kinetics of the initial steps of bacterial RNA transcription.
Our real-time kinetic analysis of promoter escape by bacterial RNA polymerase
confirms results obtained by a more indirect route, shedding additional light on
the initial steps of transcription. Finally, we discuss the advantages of our
multispot setup, while pointing potential limitations of the current single laser
excitation design, as well as analysis challenges and their solutions.
PMID- 28419143
TI - Chaetocin induces apoptosis in human melanoma cells through the generation of
reactive oxygen species and the intrinsic mitochondrial pathway, and exerts its
anti-tumor activity in vivo.
AB - Chaetocin is a small-molecule natural product produced by Chaetomium species
fungi, and it has a potent anti-proliferative pharmacological activity on various
cancer cells. However, the effect of chaetocin on anti-melanoma pharmacological
role has not been investigated. Therefore, in this study, we explored the effect
of chaetocin on cell proliferation in the human melanoma Sk-Mel-28 and A375 cells
and the growth of tumor xenografts in nude mice. The results indicated that
chaetocin treatment significantly suppressed cell proliferation and induced
apoptosis in the Sk-Mel-28 and A375 cells in a dose- and time-dependent manner.
Furthermore, chaetocin treatment resulted in an increased level of cellular
reactive oxygen species (ROS), and pre-incubation of cells with N-acetylcysteine
(NAC) significantly abrogated chaetocin-induced apoptosis in the melanoma cells.
A significant reduction of mitochondrial membrane potential and the release of
cytochrome c were observed after chaetocin treatment. Additionally, chaetocin
treatment significantly up-regulated the protein levels of Bax, cleaved caspase
9/-3, simultaneously down-regulated the protein levels of Bcl-2, procaspase-9/-3,
and activated caspase-9/-3 activity in the melanoma cells. The in vivo data
demonstrated that chaetocin treatment significantly inhibited the growth of
melanoma tumor xenografts in nude mice, which was closely associated with
apoptosis induction, a reduced level of PCNA (proliferating cell nuclear antigen)
expression, and activation of capase-9/-3 in tumor xenografts. These are the
first data to demonstrate that chaetocin exerts a proapoptotic activity on human
melanoma cells through ROS generation and the intrinsic mitochondrial pathway.
Therefore, chaetocin might represent an effective candidate for melanoma
chemotherapy.
PMID- 28419144
TI - Stepwise inhibition of T cell recruitment at post-capillary venules by orally
active desulfated heparins in inflammatory arthritis.
AB - Identification of the structure-function relationship of heparin, particularly
between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory
activities, is critical in order to evaluate the biological effects of heparin,
especially in conjunction with modifications for oral formulation. In this study,
we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic
modifications have differential effects on the blocking of interactions between
sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was
consistent with their in vivo therapeutic efficacies on CIA mice. The 6-O
desulfation of lower molecular weight heparin (LMWH) retained the ability of LMWH
to interfere with T cell adhesion via selectin-sLeX interactions. Furthermore,
6DSHbD coated on the apical surface of inflamed endothelium directly blocked the
adhesive interactions of circulating T cells, which was confirmed in vivo by
suppressing T cell adhesion at post-capillary venular endothelium. Thus, in
series with our previous study demonstrating inhibition of transendothelial
migration, oral delivery of low anticoagulant LMWH to venular endothelium of
inflamed joint tissues ameliorated arthritis by the stepwise inhibition of T cell
recruitment and provides a rationale for the development of modified oral
heparins as innovative agents for the treatment of chronic inflammatory
arthritis.
PMID- 28419145
TI - Apomixis frequency under stress conditions in weeping lovegrass (Eragrostis
curvula).
AB - To overcome environmental stress, plants develop physiological responses that are
triggered by genetic or epigenetic changes, some of which involve DNA
methylation. It has been proposed that apomixis, the formation of asexual seeds
without meiosis, occurs through the temporal or spatial deregulation of the
sexual process mediated by genetic and epigenetic factors influenced by the
environment. Here, we explored whether there was a link between the occurrence of
apomixis and various factors that generate stress, including drought stress, in
vitro culture, and intraspecific hybridization. For this purpose, we monitored
the embryo sacs of different weeping lovegrass (Eragrostis curvula [Schrad.]
Nees) genotypes after the plants were subjected to these stress conditions.
Progeny tests based on molecular markers and genome methylation status were
analyzed following the stress treatment. When grown in the greenhouse, the
cultivar Tanganyika INTA generated less than 2% of its progeny by sexual
reproduction. Plants of this cultivar subjected to different stresses showed an
increase of sexual embryo sacs, demonstrating an increased expression of
sexuality compared to control plants. Plants of the cv. Tanganyika USDA did not
demonstrate the ability to generate sexual embryo sacs under any conditions and
is therefore classified as a fully apomictic cultivar. We found that this change
in the prevalence of sexuality was correlated with genetic and epigenetic changes
analyzed by MSAP and AFLPs profiles. Our results demonstrate that different
stress conditions can alter the expression of sexual reproduction in facultative
tetraploid apomictic cultivars and when the stress stops the reproductive mode
shift back to the apomixis original level. These data together with previous
observations allow us to generate a hypothetical model of the regulation of
apomixis in weeping lovegrass in which the genetic/s region/s that condition
apomixis, is/are affected by ploidy, and is/are subjected to epigenetic control.
PMID- 28419146
TI - Household crowding as a potential mediator of socioeconomic determinants of
tuberculosis incidence in Brazil.
AB - Although many studies have identified social conditions associated with
tuberculosis, contextual and individual factors have rarely been analysed
simultaneously. Consequently, we aimed to identify contextual and individual
factors associated with tuberculosis incidence in general population in Brazil in
2010. We also assessed whether household crowding mediates the association
between socioeconomic determinants and tuberculosis incidence. Individual data of
tuberculosis cases were obtained from 5,565 municipalities in Brazil in 2010
(last year of national census), and merged with contextual variables. The
associations were evaluated in a multilevel analysis using negative binomial
regression. After adjusting for individual factors (age, sex and race) and
geographic region, the following contextual factors were associated with
tuberculosis incidence rate: AIDS incidence rate [incidence rate ratio (IRR),
1.21; 95% confidence interval (CI), 1.18-1.24], unemployment rate (IRR, 1.16; 95%
CI, 1.13-1.19), Gini coefficient (IRR, 1.05; 95% CI, 1.02-1.08), proportion of
inmates (IRR, 1.11; 95% CI, 1.09-1.14), mean per capita household income (IRR,
0.94; 95% CI, 0.91-0.97) and primary care coverage (IRR, 0.94; 95% CI, 0.92
0.96). Inclusion of household crowding in the multivariate model led to a loss of
the associations of both Gini coefficient and mean per capita household income.
In conclusion, our findings suggest that income inequality and poverty, as
determinants of tuberculosis incidence, can be mediated by household crowding.
Moreover, prison population can represent a potential social reservoir of
tuberculosis in Brazil and should be addressed as a priority for disease control.
Finally, the negative association between primary health coverage and
tuberculosis incidence highlights the importance of this level of care as a
strategy to control this disease.
PMID- 28419147
TI - Cone-beam computed tomography with automated bone subtraction in preoperative
embolization for pelvic bone tumors.
AB - PURPOSE: To evaluate the usefulness of cone-beam computed tomography with
automated bone subtraction (CBCT-ABS) in the preoperative embolization of
hypervascular tumors located in the pelvic bone. MATERIALS AND METHODS: This
retrospective study included 26 patients with pelvic bone tumors who underwent
preoperative embolization between January 2014 and October 2016. A CBCT-ABS scan
was taken in a total of 17 patients (CBCT-ABS group), and only a series of
digital subtraction angiographies (DSAs) was taken in the remaining 9 patients
(DSA group). The percent devascularization, number of angiographic runs, total
dose-area product (DAP), fluoroscopy time, interventional procedure time,
operative time, and estimated blood loss were compared between the two groups
using Mann-Whitney test. RESULTS: The percent devascularization, interventional
procedure time, fluoroscopy time, operative time, and estimated blood loss were
not statistically different between the two groups (p > 0.05). On the other hand,
the number of angiographic runs in the CBCT-ABS group was significantly lower
than that in the DSA group (p = 0.029). The total DAP of the CBCT-ABS group
(mean, 17700.7 MUGym2) was higher than that of the DSA group (mean, 8939.4
MUGym2) (p = 0.002). CONCLUSIONS: The use of CBCT-ABS during the preoperative
embolization of pelvic bone tumors significantly reduces the number of
angiographic runs at the cost of an increased radiation dose.
PMID- 28419148
TI - How long to rest in unpredictably changing habitats?
AB - In the present study, we investigated the optimum length of prolonged dormancy
(developmental arrest extending over favourable periods) of organisms under
uncertain environmental conditions. We used an artificial life model to simulate
the evolution of suspended development in the ontogenesis of organisms inhabiting
unpredictably changing habitats. A virtual population of semelparous
parthenogenetic individuals that varied in a duration of developmental arrest
competed for limited resources. At a constant level of available resources,
uninterrupted development was the superior life strategy. Once population
fluctuations appeared (generated by the stochastic variability of available
resources), temporal developmental arrest became more advantageous than
continuous development. We did not observe the selection of the optimum length of
dormancy, but rather the evolution of a diversified period of developmental
arrest. The fittest organisms employed bet-hedging strategy and produced
diversified dormant forms postponing development for a different number of
generations (from 0 to several generations, in decreasing or equal proportions).
The maximum length of suspended development increased asymptotically with
increasing environmental variability and was inversely related to the mortality
of dormant forms. The prolonged dormancy may appear beneficial not only in
erratic habitats but also in seasonal ones that are exposed to long-term
variability of environmental conditions during the growing seasons. In light of
our simulations the phenomenon of very long diapause (VLD), lasting tens to
thousands of generations, which is occasionally observed in ontogenesis of some
living creatures, may not be explained by the benefits of bet-hedging revival
strategies. We propose an alternative reasoning for the expression of VLD.
PMID- 28419149
TI - Mobile health treatment support intervention for HIV and tuberculosis in
Mozambique: Perspectives of patients and healthcare workers.
AB - BACKGROUND: Studies have been conducted in developing countries using SMS to
communicate with patients to reduce the number of missed appointments and improve
retention in treatment, however; very few have been scaled up. One possible
reason for this could be that patients or staff are dissatisfied with the method
in some way. This paper reports a study of patients' and healthcare workers'
(HCW) views on an mHealth intervention aiming to support retention in
antiretroviral therapy (ART) and tuberculosis (TB) treatment in Mozambique.
METHODS: The study was conducted at five healthcare centres in Mozambique.
Automated SMS health promotions and reminders were sent to patients in a RCT. A
total of 141 patients and 40 HCWs were interviewed. Respondents rated usefulness,
perceived benefits, ease of use, satisfaction, and risks of the SMS system using
a Likert scale questionnaire. A semi-structured interview guide was followed.
Interviews were transcribed and thematic analysis was conducted. RESULTS: Both
patients and HCW found the SMS system useful and reliable. Most highly rated
positive effects were reducing the number of failures to collect medication and
avoiding missing appointments. Patients' confidence in the system was high. Most
perceived the system to improve communication between health-care provider and
patient and assist in education and motivation. The automatic recognition of
questions from patients and the provision of appropriate answers (a unique
feature of this system) was especially appreciated. A majority would recommend
the system to other patients or healthcare centres. Risks also were mentioned,
mostly by HCW, of unintentional disclosure of health status in cases where
patients use shared phones. CONCLUSIONS: The results suggest that SMS technology
for HIV and TB should be used to transmit reminders for appointments,
medications, motivational texts, and health education to increase retention in
care. Measures must be taken to reduce risks of privacy intrusion, but these are
not a main obstacle for scaling up systems of this kind.
PMID- 28419150
TI - Disparities in dialysis allocation: An audit from the new South Africa.
AB - End Stage Kidney Disease (ESKD) is a public health problem with an enormous
economic burden. In resource limited settings management of ESKD is often
rationed. Racial and socio-economic inequalities in selecting candidates have
been previously documented in South Africa. New guidelines for dialysis developed
in the Western Cape have focused on prioritizing treatment. With this in mind we
aimed at exploring whether the new guidelines would improve inequalities
previously documented. A retrospective study of patients presented to the
selection committee was conducted at Groote Schuur Hospital. A total of 564 ESKD
patients presented between 1 January 2008 and 31 December 2012 were assessed.
Half of the patients came from low socioeconomic areas, and presentation was late
with either overt uremia (n = 181, 44.4%) or fluid overload (n = 179, 43.9%).
More than half (53.9%) of the patients were not selected for the program.
Predictors of non-acceptance onto the program included age above 50 years (OR
0.3, p = 0.001), unemployment (OR 0.3, p<0.001), substance abuse (OR 0.2,
p<0.001), diabetes (OR 0.4, p = 0.016) and a poor psychosocial assessment (OR
0.13, p<0.001). Race, gender and marital status were not predictors. The use of
new guidelines has not led to an increase in inequalities. In view of the
advanced nature of presentation greater efforts need to be made to prevent early
kidney disease, to allocate more resources to renal replacement therapy in view
of the loss of young and potentially productive life.
PMID- 28419151
TI - Skin-resident CD4+ T cells protect against Leishmania major by recruiting and
activating inflammatory monocytes.
AB - Tissue-resident memory T cells are required for establishing protective immunity
against a variety of different pathogens, although the mechanisms mediating
protection by CD4+ resident memory T cells are still being defined. In this study
we addressed this issue with a population of protective skin-resident, IFNgamma
producing CD4+ memory T cells generated following Leishmania major infection. We
previously found that resident memory T cells recruit circulating effector T
cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate
the delayed-hypersensitivity response observed in immune mice and provide
protection without circulating T cells. This protection occurs rapidly after
challenge, and requires the recruitment and activation of inflammatory monocytes,
which limit parasites by production of both reactive oxygen species and nitric
oxide. Overall, these data highlight a novel role for tissue-resident memory
cells in recruiting and activating inflammatory monocytes, and underscore the
central role that skin-resident T cells play in immunity to cutaneous
leishmaniasis.
PMID- 28419152
TI - The disadvantages of being a hybrid during drought: A combined analysis of plant
morphology, physiology and leaf proteome in maize.
AB - A comparative analysis of various parameters that characterize plant morphology,
growth, water status, photosynthesis, cell damage, and antioxidative and
osmoprotective systems together with an iTRAQ analysis of the leaf proteome was
performed in two inbred lines of maize (Zea mays L.) differing in drought
susceptibility and their reciprocal F1 hybrids. The aim of this study was to
dissect the parent-hybrid relationships to better understand the mechanisms of
the heterotic effect and its potential association with the stress response. The
results clearly showed that the four examined genotypes have completely different
strategies for coping with limited water availability and that the inherent
properties of the F1 hybrids, i.e. positive heterosis in morphological parameters
(or, more generally, a larger plant body) becomes a distinct disadvantage when
the water supply is limited. However, although a greater loss of photosynthetic
efficiency was an inherent disadvantage, the precise causes and consequences of
the original predisposition towards faster growth and biomass accumulation
differed even between reciprocal hybrids. Both maternal and paternal parents
could be imitated by their progeny in some aspects of the drought response (e.g.,
the absence of general protein down-regulation, changes in the levels of some
carbon fixation or other photosynthetic proteins). Nevertheless, other features
(e.g., dehydrin or light-harvesting protein contents, reduced chloroplast
proteosynthesis) were quite unique to a particular hybrid. Our study also
confirmed that the strategy for leaving stomata open even when the water supply
is limited (coupled to a smaller body size and some other physiological
properties), observed in one of our inbred lines, is associated with drought
resistance not only during mild drought (as we showed previously) but also during
more severe drought conditions.
PMID- 28419153
TI - Biochemical and structural investigations on phosphoribosylpyrophosphate
synthetase from Mycobacterium smegmatis.
AB - Mycobacterium smegmatis represents one model for studying the biology of its
pathogenic relative Mycobacterium tuberculosis. The structural characterization
of a M. tuberculosis ortholog protein can serve as a valid tool for the
development of molecules active against the M. tuberculosis target. In this
context, we report the biochemical and structural characterization of M.
smegmatis phosphoribosylpyrophosphate synthetase (PrsA), the ortholog of M.
tuberculosis PrsA, the unique enzyme responsible for the synthesis of
phosphoribosylpyrophosphate (PRPP). PRPP is a key metabolite involved in several
biosynthetic pathways including those for histidine, tryptophan, nucleotides and
decaprenylphosphoryl-arabinose, an essential precursor for the mycobacterial cell
wall biosynthesis. Since M. tuberculosis PrsA has been validated as a drug target
for the development of antitubercular agents, the data presented here will add to
the knowledge of the mycobacterial enzyme and could contribute to the development
of M. tuberculosis PrsA inhibitors of potential pharmacological interest.
PMID- 28419154
TI - Salt stress induces changes in the proteomic profile of micropropagated sugarcane
shoots.
AB - Salt stress is one of the most common stresses in agricultural regions worldwide.
In particular, sugarcane is affected by salt stress conditions, and no sugarcane
cultivar presently show high productivity accompanied by a tolerance to salt
stress. Proteomic analysis allows elucidation of the important pathways involved
in responses to various abiotic stresses at the biochemical and molecular levels.
Thus, this study aimed to analyse the proteomic effects of salt stress in
micropropagated shoots of two sugarcane cultivars (CB38-22 and RB855536) using a
label-free proteomic approach. The mass spectrometry proteomics data are
available via ProteomeXchange with identifier PXD006075. The RB855536 cultivar is
more tolerant to salt stress than CB38-22. A quantitative label-free shotgun
proteomic analysis identified 1172 non-redundant proteins, and 1160 of these were
observed in both cultivars in the presence or absence of NaCl. Compared with CB38
22, the RB855536 cultivar showed a greater abundance of proteins involved in non
enzymatic antioxidant mechanisms, ion transport, and photosynthesis. Some
proteins, such as calcium-dependent protein kinase, photosystem I, phospholipase
D, and glyceraldehyde-3-phosphate dehydrogenase, were more abundant in the
RB855536 cultivar under salt stress. Our results provide new insights into the
response of sugarcane to salt stress, and the changes in the abundance of these
proteins might be important for the acquisition of ionic and osmotic homeostasis
during exposure to salt stress.
PMID- 28419155
TI - Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage
degeneration in an experimental rat osteoarthritis model.
AB - Mesenchymal stem cell (MSC)-based cell therapy is a promising avenue for
osteoarthritis (OA) treatment. In the present study, we evaluated the efficacy of
intra-articular injections of culture-expanded allogenic adipose tissue-derived
stem cells (ADSCs) for the treatment of anterior cruciate ligament transection
(ACLT) induced rat OA model. The paracrine effects of major histocompatibility
complex (MHC)-unmatched ADSCs on chondrocytes were investigated in vitro. Rats
were divided into an OA group that underwent ACLT surgery and a sham-operated
group that did not undergo ACLT surgery. Four weeks after surgery mild OA was
induced in the OA group. Subsequently, the OA rats were randomly divided into
ADSC and control groups. A single dose of 1 * 106 ADSCs suspended in 60 MUL
phosphate-buffered saline (PBS) was intra-articularly injected into the rats of
the ADSC group. The control group received only 60 MUL PBS. OA progression was
evaluated macroscopically and histologically at 8 and 12 weeks after surgery.
ADSC treatment did not cause any adverse local or systemic reactions. The
degeneration of articular cartilage was significantly weaker in the ADSC group
compared to that in the control group at both 8 and 12 weeks. Chondrocytes were
co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine
effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1beta
induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and
MMP-13 and the pro-inflammatory cytokines TNF-alpha and IL-6 in chondrocytes.
Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL
10 in chondrocytes. The results of this study indicated that the intra-articular
injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration
in an experimental rat OA model without inducing any adverse reactions. MHC
unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage.
The paracrine effects of ADSCs on OA chondrocytes are at least part of the
mechanism by which ADSCs exert their therapeutic activity.
PMID- 28419156
TI - School nurses' attitudes towards and experiences of the Swedish school-based HPV
vaccination programme - A repeated cross sectional study.
AB - The aim was to investigate school nurses' attitudes towards, and experiences of
vaccination against human papillomavirus (HPV), and compare the results with a
similar study three years earlier. School nurses (n = 736) from all counties in
Sweden completed a questionnaire in spring 2016, four years after the
implementation of the national HPV vaccination programme, and three years after
the previous survey. Overall, the school nurses had more favourable attitudes
towards the HPV vaccination programme compared to the study in 2013 (p = 0.015).
More than half of the nurses (n = 415, 56%) strongly agreed that boys should also
be offered the vaccine (p<0.001). There were no differences in school nurses'
perceived knowledge about HPV in order to inform and to answer questions about
the vaccine from the girls or from the parents. More than half of the nurses (n =
409, 56%) reported that they needed more education about HPV. Almost all nurses
(n = 659, 90%) had been contacted by parents with questions about the vaccine,
and most questions were related to vaccine safety. School nurses have a more
favourable attitude towards the vaccination programme against HPV compared to
three years earlier, although almost all nurses had been contacted by parents
with diverse questions and concerns. The nurses believed that they needed more
education about HPV. Thus, it is essential to provide ongoing education and
training for school nurses who are key healthcare professionals for providing
information about HPV and HPV vaccination to parents and to pupils.
PMID- 28419157
TI - The analysis of viability for mammalian cells treated at different temperatures
and its application in cell shipment.
AB - Mammalian cells are very important experimental materials and widely used in
biological and medical research fields. It is often required that mammalian cells
are transported from one laboratory to another to meet with various researches.
Conventional methods for cell shipment are laborious and costive despite of
maintaining high viability. In this study we aimed to develop a simple and low
cost method for cell shipment by investigating the viabilities of different cell
lines treated at different temperatures. We show that the viability of mammalian
cells incubated at 1 degrees C or 5 degrees C significantly reduced when compared
with that at 16 degrees C or 22 degrees C. Colony formation assays revealed that
preservation of mammalian cells at 1 degrees C or 5 degrees C led to a poorer
recovery than that at 16 degrees C or 22 degrees C. The data from proliferation
and apoptotic assays confirmed that M2 cells could continue to proliferate at 16
degrees C or 22 degrees C, but massive death was caused by apoptosis at 1 degrees
C or 5 degrees C. The morphology of mammalian cells treated under hypothermia
showed little difference from that of the untreated cells. Quantitative RT-PCR
and alkaline phosphatase staining confirmed that hypothermic treatment did not
change the identity of mouse embryonic stem cells. A case study showed that
mammalian cells directly suspended in culture medium were able to be shipped for
long distance and maintained a high level of viability and recovery. Our findings
not only broaden the understanding to the effect of hypothermia on the viability
of mammalian cells, but also provide an alternative approach for cell shipment.
PMID- 28419158
TI - Identification of pre-fertilization reproductive barriers and the underlying
cytological mechanism in crosses among three petal-types of Jasminum sambac and
their relevance to phylogenetic relationships.
AB - Crosses among single-, double- and multi-petal jasmine cultivars (Jasminum sambac
Aiton) are unable to easily generate hybrids. To identify the reproductive
barriers restricting hybrid set, dynamic changes in jasmine pollen viability and
pistil receptivity were compared at different flowering stages. Pollen-pistil
interactions in six reciprocal crosses were also investigated to characterize
pollen-stigma compatibility. Additionally, paraffin sections of pollinated embryo
sacs were prepared for subsequent analyses of developmental status. Furthermore,
pistil cell ultrastructural characteristics were observed to reveal cytological
mechanism regulating pistil receptivity and the pollen-pistil interactions. We
observed that pollen viability and stigma receptivity varied depending on petal
phenotype and flowering stage and were easily lost during flowering. Different
reciprocal crosses exhibited varied pollen-stigma compatibilities according to
the pollen germination rates. Although some pollen grains germinated normally on
maternal stigmas, the pollen tubes were arrested in the pistils and were unable
to reach the ovaries. Additionally, the embryo sacs remained unfertilized until
degenerating. Therefore, jasmine crosses are affected by pre-fertilization
reproductive barriers. Low pollen fertility and poor stigma receptivity are
detrimental to pollen germination and pollen-pistil compatibility, indicating
they are two factors affecting hybrid set. Ultrastructural observation of the
pistil cells revealed that cell death occurred during flowering. Thus, the early
and rapid senescence of pistils is likely responsible for the decreased pistil
receptivity and inhibited pollen tube growth. These findings may be relevant for
future jasmine hybridizations. They provide new insights for the development of
methods to overcome reproductive barriers and may also be useful for clarifying
the phylogenetic relationships among jasmine cultivars with differing petal
phenotypes.
PMID- 28419159
TI - Oral potassium supplementation for management of essential hypertension: A meta
analysis of randomized controlled trials.
AB - IMPORTANCE: Increased dietary potassium intake is thought to be associated with
low blood pressure (BP). Whether potassium supplementation may be used as an
antihypertensive agent is a question that should be answered. OBJECTIVE: To
assess the effect of oral potassium supplementation on blood pressure in patients
with primary hypertension. SEARCH METHODS: We searched Medline, Web of Science,
Scopus, Cochrane Central Register of Controlled Trials until October 2016. We
also screened reference lists of articles and previous reviews. We applied no
language restrictions. SELECTION CRITERIA: We included randomized placebo
controlled clinical trials addressing the effect of potassium supplementation on
primary hypertension for a minimum of 4 weeks. DATA COLLECTION AND ANALYSIS: We
extracted data on systolic and diastolic BP (SBP and DBP) at the final follow-up.
We explored the heterogeneity across studies using Cochran's test and I2
statistic and assessed the probability of publication bias using Begg's and
Egger's tests. We reported the mean difference (MD) of SBP and DBP in a random
effects model. RESULTS: We found a total of 9059 articles and included 23 trials
with 1213 participants. Compared to placebo, potassium supplementation resulted
in modest but significant reductions in both SBP (MD -4.25 mmHg; 95% CI: -5.96 to
-2.53; I2 = 41%) and DBP (MD -2.53 mmHg; 95% CI: -4.05 to -1.02; I2 = 65%).
According to the change-score analysis, based on 8 out of 23 trials, compared to
baseline, the mean changes in SBP (MD -8.89 mmHg; 95% CI: -13.67 to -4.11) and
DBP (MD -6.42 mmHg; 95% CI: -10.99 to -1.84) was significantly higher in the
intervention group than the control group. CONCLUSIONS: Our findings indicated
that potassium supplementation is a safe medication with no important adverse
effects that has a modest but significant impact BP and may be recommended as an
adjuvant antihypertensive agent for patients with essential hypertension.
PMID- 28419160
TI - An empirically grounded agent based model for modeling directs, conflict
detection and resolution operations in air traffic management.
AB - We present an agent based model of the Air Traffic Management socio-technical
complex system aiming at modeling the interactions between aircraft and air
traffic controllers at a tactical level. The core of the model is given by the
conflict detection and resolution module and by the directs module. Directs are
flight shortcuts that are given by air controllers to speed up the passage of an
aircraft within a certain airspace and therefore to facilitate airline
operations. Conflicts between flight trajectories can occur for two main reasons:
either the planning of the flight trajectory was not sufficiently detailed to
rule out all potential conflicts or unforeseen events during the flight require
modifications of the flight plan that can conflict with other flight
trajectories. Our model performs a local conflict detection and resolution
procedure. Once a flight trajectory has been made conflict-free, the model
searches for possible improvements of the system efficiency by issuing directs.
We give an example of model calibration based on real data. We then provide an
illustration of the capability of our model in generating scenario simulations
able to give insights about the air traffic management system. We show that the
calibrated model is able to reproduce the existence of a geographical
localization of air traffic controllers' operations. Finally, we use the model to
investigate the relationship between directs and conflict resolutions (i) in the
presence of perfect forecast ability of controllers, and (ii) in the presence of
some degree of uncertainty in flight trajectory forecast.
PMID- 28419161
TI - Unidentifiable by morphology: DNA barcoding of plant material in local markets in
Iran.
AB - Local markets provide a rapid insight into the medicinal plants growing in a
region as well as local traditional health concerns. Identification of market
plant material can be challenging as plants are often sold in dried or processed
forms. In this study, three approaches of DNA barcoding-based molecular
identification of market samples are evaluated, two objective sequence matching
approaches and an integrative approach that coalesces sequence matching with a
priori and a posteriori data from other markers, morphology, ethnoclassification
and species distribution. Plant samples from markets and herbal shops were
identified using morphology, descriptions of local use, and vernacular names with
relevant floras and pharmacopoeias. DNA barcoding was used for identification of
samples that could not be identified to species level using morphology. Two
methods based on BLAST similarity-based identification, were compared with an
integrative identification approach. Integrative identification combining the
optimized similarity-based approach with a priori and a posteriori information
resulted in a 1.67, 1.95 and 2.00 fold increase for ITS, trnL-F spacer, and both
combined, respectively. DNA barcoding of traded plant material requires objective
strategies to include data from multiple markers, morphology, and traditional
knowledge to optimize species level identification success.
PMID- 28419162
TI - Symmetry based assembly of a 2 dimensional protein lattice.
AB - The design of proteins that self-assemble into higher order architectures is of
great interest due to their potential application in nanotechnology.
Specifically, the self-assembly of proteins into ordered lattices is of special
interest to the field of structural biology. Here we designed a 2 dimensional
(2D) protein lattice using a fusion of a tandem repeat of three TelSAM domains
(TTT) to the Ferric uptake regulator (FUR) domain. We determined the structure of
the designed (TTT-FUR) fusion protein to 2.3 A by X-ray crystallographic methods.
In agreement with the design, a 2D lattice composed of TelSAM fibers
interdigitated by the FUR domain was observed. As expected, the fusion of a
tandem repeat of three TelSAM domains formed 21 screw axis, and the self-assembly
of the ordered oligomer was under pH control. We demonstrated that the fusion of
TTT to a domain having a 2-fold symmetry, such as the FUR domain, can produce an
ordered 2D lattice. The TTT-FUR system combines features from the rotational
symmetry matching approach with the oligomer driven crystallization method. This
TTT-FUR fusion was amenable to X-ray crystallographic methods, and is a promising
crystallization chaperone.
PMID- 28419163
TI - Response of microbial community of organic-matter-impoverished arable soil to
long-term application of soil conditioner derived from dynamic rapid fermentation
of food waste.
AB - Rapid fermentation of food waste can be used to prepare soil conditioner. This
process consumes less time and is more cost-effective than traditional
preparation technology. However, the succession of the soil microbial community
structure after long-term application of rapid fermentation-derived soil
conditioners remains unclear. Herein, dynamic rapid fermentation (DRF) of food
waste was performed to develop a soil conditioner and the successions and
diversity of bacterial communities in an organic-matter-impoverished arable soil
after six years of application of DRF-derived soil conditioner were investigated.
Results showed that the treatment increased soil organic matter (SOM)
accumulation and strawberry yield by 5.3 g/kg and 555.91 kg/ha, respectively.
Proteobacteria, Actinobacteria, Acidobacteria, and Firmicutes became the dominant
phyla, occupying 65.95%-77.52% of the bacterial sequences. Principal component
analysis (PCA) results showed that the soil bacterial communities were largely
influenced by the treatment. Redundancy analysis (RDA) results showed that the
relative abundances of Gemmatimonadetes, Chloroflexi, Verrucomicrobia,
Nitrospirae, and Firmicutes were significantly correlated with soil TC, TN, TP,
NH4+-N, NO3--N, OM, and moisture. These communities were all distributed in the
soil samples collected in the sixth year of application. Long-term treatment did
not enhance the diversity of bacterial species but significantly altered the
distribution of major functional bacterial communities in the soils. Application
of DRF-derived soil conditioner could improve the soil quality and optimize the
microbial community, ultimately enhancing fruit yields.
PMID- 28419164
TI - Population pharmacokinetic modelling of rupatadine solution in 6-11 year olds and
optimisation of the experimental design in younger children.
AB - AIMS: To optimise a pharmacokinetic (PK) study design of rupatadine for 2-5 year
olds by using a population PK model developed with data from a study in 6-11 year
olds. The design optimisation was driven by the need to avoid children's
discomfort in the study. METHODS: PK data from 6-11 year olds with allergic
rhinitis available from a previous study were used to construct a population PK
model which we used in simulations to assess the dose to administer in a study in
2-5 year olds. In addition, an optimal design approach was used to determine the
most appropriate number of sampling groups, sampling days, total samples and
sampling times. RESULTS: A two-compartmental model with first-order absorption
and elimination, with clearance dependent on weight adequately described the PK
of rupatadine for 6-11 year olds. The dose selected for a trial in 2-5 year olds
was 2.5 mg, as it provided a Cmax below the 3 ng/ml threshold. The optimal study
design consisted of four groups of children (10 children each), a maximum
sampling window of 2 hours in two clinic visits for drawing three samples on day
14 and one on day 28 coinciding with the final examination of the study.
CONCLUSIONS: A PK study design was optimised in order to prioritise avoidance of
discomfort for enrolled 2-5 year olds by taking only four blood samples from each
child and minimising the length of hospital stays.
PMID- 28419165
TI - Soaking suggests "alternative facts": Only co-crystallization discloses major
ligand-induced interface rearrangements of a homodimeric tRNA-binding protein
indicating a novel mode-of-inhibition.
AB - For the efficient pathogenesis of Shigella, the causative agent of bacillary
dysentery, full functionality of tRNA-guanine transglycosylase (TGT) is
mandatory. TGT performs post-transcriptional modifications of tRNAs in the
anticodon loop taking impact on virulence development. This suggests TGT as a
putative target for selective anti-shigellosis drug therapy. Since bacterial TGT
is only functional as homodimer, its activity can be inhibited either by blocking
its active site or by preventing dimerization. Recently, we discovered that in
some crystal structures obtained by soaking the full conformational adaptation
most likely induced in solution upon ligand binding is not displayed. Thus,
soaked structures may be misleading and suggest irrelevant binding modes.
Accordingly, we re-investigated these complexes by co-crystallization. The
obtained structures revealed large conformational rearrangements not visible in
the soaked complexes. They result from spatial perturbations in the ribose
34/phosphate-35 recognition pocket and, consequently, an extended loop-helix
motif required to prevent access of water molecules into the dimer interface
loses its geometric integrity. Thermodynamic profiles of ligand binding in
solution indicate favorable entropic contributions to complex formation when
large conformational adaptations in the dimer interface are involved. Native MS
titration experiments reveal the extent to which the homodimer is destabilized in
the presence of each inhibitor. Unexpectedly, one ligand causes a complete
rearrangement of subunit packing within the homodimer, never observed in any
other TGT crystal structure before. Likely, this novel twisted dimer is
catalytically inactive and, therefore, suggests that stabilizing this non
productive subunit arrangement may be used as a further strategy for TGT
inhibition.
PMID- 28419166
TI - Comparison of standardized uptake value of 18F-FDG-PET-CT with 21-gene recurrence
score in estrogen receptor-positive, HER2-negative breast cancer.
AB - BACKGROUND: We investigated the relationship between 18F-fluorodeoxyglucose
positron emission tomography-computed tomography (18F-FDG-PET-CT) standardized
uptake value (SUV) and 21-gene recurrence score (RS) in estrogen receptor (ER)
positive/HER2-negative breast cancer. MATERIALS AND METHODS: One hundred sixty
seven patients were identified among those who underwent preoperative 18F-FDG-PET
CT and had RS. Maximum SUV was obtained from 18F-FDG-PET-CT; the cut-off point
was 4. RESULTS: The continuous RS and SUV correlated positively (Pearson's R =
0.555; P < 0.001). An inverse correlation was found between progesterone receptor
(PR) expression by reverse transcriptase-polymerase chain reaction, and SUV
(Pearson's R = -0.408; P < 0.001). Good agreement between dichotomized RS (<26
vs. >=26) and SUV (<4 vs. >=4) was observed in 137 of 167 patients (82.0%; 95%
confidence interval [CI], 76.2-87.9). Among patients with low SUV, 114 of 115
(99.1% [95% CI, 97.4-100.0]) had tumors with lower RS (<26). Although 23 of 52
women (44.2% [95% CI, 30.7-57.7]) with high SUV had higher RS (>=26), all 13
women with high RS (>=31) had high-SUV tumors. Most cases with disagreements
between SUV and RS (n = 30) were classified as high SUV/lower RS (n = 29). The
discordant group had higher grade or elevated Ki67 expression (>=20%) compared
with the low SUV/lower RS group (n = 109), but higher PR expression compared with
the high SUV/higher RS group (n = 23). Multiple logistic regression analysis
showed that high SUV were associated with higher RS (>=26). CONCLUSIONS: SUV, as
a biologic parameter represented using a continuous variable, was found to
associate with RS in ER-positive, HER2-negative breast cancer. Further studies
may reveal the biology underlying the discordance between the markers.
PMID- 28419167
TI - Pharmacy students' anxiety towards research during their undergraduate degree;
How to reduce it?
AB - OBJECTIVE: To measure pharmacy students' anxiety towards research and how
academic support, academic effort, attitude and self-efficacy influence their
research anxiety. METHODS: A cross-sectional study was conducted with
undergraduate final year students of pharmacy using a convenient sampling method.
A validated self-administered questionnaire was used. RESULTS: Response rate for
this study was 85.9% (128 students from a population of 149). The participants
agreed that they read literature to understand research, but did not attend
research-related coursework. Most participants (91.4%) felt that they were under
stress while doing research. Almost all participants (97.6%) felt that they were
doing very badly during their data analysis or they may fail their research
projects. The majority of participants agreed that help from the lecturers' and
friends in research give emotional support for their research activities.
CONCLUSION: Academic support for pharmacy students, along with their additional
academic effort will improve the students' self-efficacy and reduce research
anxiety.
PMID- 28419168
TI - Dynamic patterns of expression for genes regulating cytokinin metabolism and
signaling during rice inflorescence development.
AB - Inflorescence development in cereals, including such important crops as rice,
maize, and wheat, directly affects grain number and size and is a key determinant
of yield. Cytokinin regulates meristem size and activity and, as a result, has
profound effects on inflorescence development and architecture. To clarify the
role of cytokinin action in inflorescence development, we used the NanoString
nCounter system to analyze gene expression in the early stages of rice panicle
development, focusing on 67 genes involved in cytokinin biosynthesis,
degradation, and signaling. Results point toward key members of these gene
families involved in panicle development and indicate that the expression of many
genes involved in cytokinin action differs between the panicle and vegetative
tissues. Dynamic patterns of gene expression suggest that subnetworks mediate
cytokinin action during different stages of panicle development. The variation of
expression during panicle development is greater among genes encoding proteins
involved in cytokinin metabolism and negative regulators of the pathway than for
the genes in the primary response pathway. These results provide insight into the
expression patterns of genes involved in cytokinin action during inflorescence
development in a crop of agricultural importance, with relevance to similar
processes in other monocots. The identification of subnetworks of genes expressed
at different stages of early panicle development suggests that manipulation of
their expression could have substantial effects on inflorescence architecture.
PMID- 28419169
TI - Decomposing functional trait associations in a Chinese subtropical forest.
AB - Functional traits, properties of organisms correlated with ecological
performance, play a central role in plant community assembly and functioning. To
some extents, functional traits vary in concert, reflecting fundamental
ecological strategies. While "trait syndromes" characteristic of e.g. fast
growing, early-successional vs. competitive, late-successional species are
recognized in principle, less is known about the environmental and genetic
factors at the source of trait variation and covariation within plant
communities. We studied the three leaf traits leaf half-life (LHL), leaf mass per
area (LMA) and nitrogen concentration in green leaves (Ngreen) and the wood trait
wood density (WD) in 294 individuals belonging to 45 tree or shrub species in a
Chinese subtropical forest from September 2006 to January 2009. Using multilevel
ANOVA and decomposition of sums of products, we estimated the amount of trait
variation and covariation among species (mainly genetic causes), i.e. plant
functional type (deciduous vs. evergreen species), growth form (tree vs. shrub
species), family/genus/species differences, and within species (mainly
environmental causes), i.e. individual and season. For single traits, the
variation between functional types and among species within functional types was
large, but only LMA and Ngreen varied significantly among families and thus
showed phylogenetic signal. Trait variation among individuals within species was
small, but large temporal variation due to seasonal effects was found within
individuals. We did not find any trait variation related to soil conditions
underneath the measured individuals. For pairs of traits, variation between
functional types and among species within functional types was large, reflecting
a strong evolutionary coordination of the traits, with LMA, LHL and WD being
positively correlated among each other and negatively with Ngreen. This
integration of traits was consistent with a putative stem-leaf economics spectrum
ranging from deciduous species with thin, high-nitrogen leaves and low-density
wood to evergreen species with thick, low-nitrogen leaves and dense wood and was
not influenced by phylogenetic history. Trait coordination within species was
weak, allowing individual trees to deviate from the interspecific trait
coordination and thus respond flexibly to environmental heterogeneity. Our
findings suggest that within a single woody plant community variation and
covariation in functional traits allows a large number of species to co-exist and
cover a broad spectrum of multivariate niche space, which in turn may increase
total resource extraction by the community and community functioning.
PMID- 28419170
TI - Evaluation of the relative efficacy of a couple cognitive-behaviour therapy (CBT)
for Premenstrual Disorders (PMDs), in comparison to one-to-one CBT and a wait
list control: A randomized controlled trial.
AB - DESIGN: A randomised control trial (RCT) was conducted to examine the efficacy of
couple-based cognitive behaviour therapy (CBT) for Premenstrual Disorders (PMDs),
in comparison to one-to-one CBT and a wait-list control. METHODS: Triangulation
of quantitative and qualitative outcome measures evaluated changes pre-post
intervention. Eighty three women were randomly allocated across three conditions,
with 63 completing post-intervention measures, a retention rate of 76%. RESULTS:
Repeated measures analysis of variance found a significant time by group
interaction identifying that women in the two CBT conditions reported lower total
premenstrual symptoms, emotional reactivity/mood, and premenstrual distress, in
comparison to the wait list control. Significantly higher active behavioural
coping post-intervention was found in the couple condition than in the one-to-one
and wait list control groups. Qualitative analysis provided insight into the
subjective experience of PMDs and participation in the intervention study. Across
groups, women reported increased awareness and understanding of premenstrual
change post-intervention. A larger proportion of women in the CBT conditions
reported reduction in intensity and frequency of negative premenstrual emotional
reactivity, increased communication and help-seeking, increased understanding and
acceptance of embodied change, and the development of coping skills, post
intervention. Increased partner understanding and improved relationship post
intervention was reported by a greater proportion of participants in the CBT
conditions, most markedly in the couple condition. CONCLUSION: These findings
suggest that one-to-one and couple CBT interventions can significantly reduce
women's premenstrual symptomatology and distress, and improve premenstrual
coping. Couple based CBT interventions may have a greater positive impact upon
behavioural coping and perceptions of relationship context and support. This
suggests that CBT should be available for women reporting moderate-severe PMDs,
with couple-based CBT offering additional benefits to a one-to-one modality.
PMID- 28419171
TI - Ultrasound texture analysis: Association with lymph node metastasis of papillary
thyroid microcarcinoma.
AB - This retrospective study aimed to evaluate whether ultrasound texture analysis is
useful to predict lymph node metastasis in patients with papillary thyroid
microcarcinoma (PTMC). This study was approved by the Institutional Review Board,
and the need to obtain informed consent was waived. Between May and July 2013,
361 patients (mean age, 43.8 +/- 11.3 years; range, 16-72 years) who underwent
staging ultrasound (US) and subsequent thyroidectomy for conventional PTMC <= 10
mm between May and July 2013 were included. Each PTMC was manually segmented and
its histogram parameters (Mean, Standard deviation, Skewness, Kurtosis, and
Entropy) were extracted with Matlab software. The mean values of histogram
parameters and clinical and US features were compared according to lymph node
metastasis using the independent t-test and Chi-square test. Multivariate
logistic regression analysis was performed to identify the independent factors
associated with lymph node metastasis. Tumors with lymph node metastasis (n =
117) had significantly higher entropy compared to those without lymph node
metastasis (n = 244) (mean+/-standard deviation, 6.268+/-0.407 vs. 6.171+/
.0.405; P = .035). No additional histogram parameters showed differences in mean
values according to lymph node metastasis. Entropy was not independently
associated with lymph node metastasis on multivariate logistic regression
analysis (Odds ratio, 0.977 [95% confidence interval (CI), 0.482-1.980]; P =
.949). Younger age (Odds ratio, 0.962 [95% CI, 0.940-0.984]; P = .001) and lymph
node metastasis on US (Odds ratio, 7.325 [95% CI, 3.573-15.020]; P < .001) were
independently associated with lymph node metastasis. Texture analysis was not
useful in predicting lymph node metastasis in patients with PTMC.
PMID- 28419172
TI - Enhanced disease resistance and drought tolerance in transgenic rice plants
overexpressing protein elicitors from Magnaporthe oryzae.
AB - Exogenous application of the protein elicitors MoHrip1 and MoHrip2, which were
isolated from the pathogenic fungus Magnaporthe oryzae (M. oryzae), was
previously shown to induce a hypersensitive response in tobacco and to enhance
resistance to rice blast. In this work, we successfully transformed rice with the
mohrip1 and mohrip2 genes separately. The MoHrip1 and MoHrip2 transgenic rice
plants displayed higher resistance to rice blast and stronger tolerance to
drought stress than wild-type (WT) rice and the vector-control pCXUN rice. The
expression of salicylic acid (SA)- and abscisic acid (ABA)-related genes was also
increased, suggesting that these two elicitors may trigger SA signaling to
protect the rice from damage during pathogen infection and regulate the ABA
content to increase drought tolerance in transgenic rice. Trypan blue staining
indicated that expressing MoHrip1 and MoHrip2 in rice plants inhibited hyphal
growth of the rice blast fungus. Relative water content (RWC), water usage
efficiency (WUE) and water loss rate (WLR) were measured to confirm the high
capacity for water retention in transgenic rice. The MoHrip1 and MoHrip2
transgenic rice also exhibited enhanced agronomic traits such as increased plant
height and tiller number.
PMID- 28419173
TI - Sponge symbioses between Xestospongia deweerdtae and Plakortis spp. are not
motivated by shared chemical defense against predators.
AB - The recently described epizoic sponge-sponge symbioses between Xestospongia
deweerdtae and two species of Plakortis present an unusual series of sponge
interactions. Sponges from the genus Plakortis are fierce allelopathic
competitors, rich in cytotoxic secondary metabolites, and yet X. deweerdtae
flourishes as an epizoic encrustation on Plakortis deweerdtaephila and Plakortis
symbiotica. Our objective in this study was to evaluate the hypothesis that X.
deweerdtae grows epizoic to these two species of Plakortis due to a shared
chemical defense against predators. We collected free-living individuals of X.
deweerdtae and symbiotic pairs from a wide geographical range to generate crude
organic extracts and a series of polarity fractions from sponge extract. We
tested the deterrency of these extracts against three common coral reef
predators: the bluehead wrasse, Thalassoma bifasciatum, the Caribbean sharpnose
puffer, Canthigaster rostrata, and the white spotwrist hermit crab, Pagurus
criniticornis. While the chemical defenses of P. deweerdtaephila and P.
symbiotica are more potent than those of X. deweerdtae, all of the sponge species
we tested significantly deterred feeding in all three generalist predators. The
free-living form of X. deweerdtae is mostly defended across the region, with a
few exceptions. The associated form of X. deweerdtae is always defended, and both
species of Plakortis are very strongly defended, with puffers refusing to consume
extract-treated pellets until the extract was diluted to 1/256* concentration.
Using diode-array high performance liquid chromatography (HPLC) coupled with high
resolution mass spectrometry (LC-MS/IT-TOF), we found two secondary metabolites
from P. deweerdtaephila, probably the cyclic endoperoxides plakinic acid I and
plakinic acid K, in low concentrations in the associated-but not the free-living
form of X. deweerdtae, suggesting a possible translocation of defensive chemicals
from the basibiont to the epibiont. Comparing the immense deterrency of Plakortis
spp. extracts to the extracts of X. deweerdtae gives the impression that there
may be some sharing of chemical defenses: one partner in the symbiosis is clearly
more defended than the other and a small amount of its defensive chemistry may
translocate to the partner. However, X. deweerdtae effectively deters predators
with its own defensive chemistry. Multiple lines of evidence provide no support
for the shared chemical defense hypothesis. Given the diversity of other
potential food resources available to predators on coral reefs, it is improbable
that the evolution of these specialized sponge-sponge symbioses has been driven
by predation pressure.
PMID- 28419174
TI - Stronger diversity effects with increased environmental stress: A study of
multitrophic interactions between oak, powdery mildew and ladybirds.
AB - Recent research has suggested that increasing neighbourhood tree species
diversity may mitigate the impact of pests or pathogens by supporting the
activities of their natural enemies and/or reducing the density of available
hosts. In this study, we attempted to assess these mechanisms in a multitrophic
study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe
spp.) and a mycophagous ladybird (Psyllobora vigintiduopunctata). We assessed
ladybird mycophagy on oak PM in function of different neighbourhood tree species
compositions. We also evaluated whether these species interactions were modulated
by environmental conditions as suggested by the Stress Gradient Hypothesis. We
adopted a complementary approach of a field experiment where we monitored oak
saplings subjected to a reduced rainfall gradient in a young planted forest
consisting of different tree species mixtures, as well as a lab experiment where
we independently evaluated the effect of different watering treatments on PM
infections and ladybird mycophagy. In the field experiment, we found effects of
neighbourhood tree species richness on ladybird mycophagy becoming more positive
as the target trees received less water. This effect was only found as weather
conditions grew drier. In the lab experiment, we found a preference of ladybirds
to graze on infected leaves from trees that received less water. We discuss
potential mechanisms that might explain this preference, such as emissions of
volatile leaf chemicals. Our results are in line with the expectations of the
Natural Enemies Hypothesis and support the hypothesis that biodiversity effects
become stronger with increased environmental stress.
PMID- 28419175
TI - Talent identification and recruitment in youth soccer: Recruiter's perceptions of
the key attributes for player recruitment.
AB - Using the modified Delphi method, we aimed to understand the attributes youth
coaches and recruiters perceive as important when identifying skilled youth
performance at the entry level of representative soccer in Australia (i.e., Under
13 years). Furthermore, we also aimed to describe the current methods youth
coaches and recruiters use to assess and identify these attributes in youth
players. Australian regional youth technical directors and coaches (n = 20)
completed a three stage process, including an initial interview and two
subsequent questionnaires, whereby attributes and qualities associated with
talent identification were rated and justified according to the importance for
youth player performance and talent identification. Results indicate a hierarchy
of attributes recruiters perceive as important for Under 13 soccer performance,
including technical (i.e., first touch, striking the ball, one-versus-one
ability, and technical ability under pressure), tactical (i.e., decision-making
ability) and psychological attributes (i.e., coachability and positive attitude).
In addition, the findings indicated attributes and qualities not emphasised
within the talent identification process including, physiological,
anthropometrical, sociological and several psychological attributes. It is
suggested talent recruiters apply a holistic multidisciplinary approach to talent
identification, with the current findings potentially providing initial evidence
to suggest recruiters do consider numerous attributes when selecting and
identifying youth players.
PMID- 28419176
TI - MICA diversity and linkage disequilibrium with HLA-B alleles in renal-transplant
candidates in southern Brazil.
AB - The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is
located centromerically to the human leukocyte antigen (HLA)-B. The short
distance between these loci in the MHC indicates the presence of linkage
disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and
this polymorphism has not been well documented in different populations. In this
study, we estimated the allelic frequencies of MICA and the linkage
disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern
Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence
specific primer method (PCR-SSO), combined with the Luminex technology. A total
of 19 MICA allele groups were identified. The most frequent allele groups were
MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common
haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35
(5.63%). As expected from the proximity of the MICA and HLA-B loci, most
haplotypes showed strong LD. Renal patients and healthy subjects in the same
region of Brazil showed statistically significant differences in their MICA
polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc
= 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was
more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469).
This study provided information on the distribution of MICA polymorphisms and
linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant
candidates. This information should help to determine the mechanisms of
susceptibility to different diseases in patients with chronic kidney disease, and
to elucidate the mechanisms involved in allograft rejection associated with MICA
polymorphisms in a Brazilian population.
PMID- 28419177
TI - Interpreting Patterns of Low Scores on the NIH Toolbox Cognition Battery.
AB - Introduction: The National Institutes of Health Toolbox for Assessment of
Neurological and Behavioral Function Cognition Battery is comprised of seven
cognitive tests, including two tests measuring crystallized cognitive ability
(i.e., vocabulary and reading) and five tests measuring fluid cognitive
functioning (i.e., working memory, memory, speed of processing, and executive
functioning). This study presents comprehensive base rate tables for the
frequency of low scores in adults and older adults from the normative sample.
Methods: Participants were 843 adults, ages 20-85, from the NIH Toolbox
standardization sample who completed all seven cognition tests. Rates of low
scores were derived for standard age-adjusted and fully-demographically-adjusted
scores at multiple cut-scores. Base rates were stratified by education,
crystallized intellectual ability, and cognitive domain. Results: Using the five
demographically-adjusted fluid cognitive test scores, 45.9% of adults obtained
one or more scores at or below the 16th percentile, and 16.8% obtained one or
more score at or below the 5th percentile, which is consistent with findings from
other neurocognitive test batteries. Discussion: Based on the study findings,
nearly 50% of adults in the general population would meet psychometric criteria
for a diagnosis of the Diagnostic and Statistical Manual of Mental Disorders
Fifth Edition (DSM-5) Mild Neurocognitive Disorder (MND). We developed new
psychometric criteria for identifying MND using the NIH Toolbox Cognition Battery
that reduce the false positive rate. Knowing these multivariate normative base
rates will help researchers and clinicians interpret NIH Toolbox scores in people
with neurodevelopmental, psychiatric, medical, neurological, and
neurodegenerative disorders that affect cognitive functioning.
PMID- 28419178
TI - Acquiring evidence for precision prostate cancer care.
PMID- 28419179
TI - The Intensity of Brief Interventions in Patients with Acute Alcoholic
Pancreatitis Should be Increased, Especially in Young Patients with Heavy Alcohol
Consumption.
AB - Aims: After the first acute alcoholic pancreatitis (AAP), active repeated brief
interventions (BIs) have been shown to protect against recurrent acute
pancreatitis (RAP). However, in daily hospital practice the treatment of alcohol
problems varies. Our aim was to study BIs performed in the clinic during AAP and
whether this prevents from future RAP episodes. Methods: Data on all patients
discharged between 10/2010 and 10/2012 with acute pancreatitis as the primary
diagnosis were obtained from the hospital database. Patients with the first
attack of AAP were included in the study. Documented BIs during hospitalization
for AAP and RAP and the development of RAP and chronic pancreatitis during median
(range) follow-up of 4.2 (0.2-6.1) years were analyzed. Patients were also
contacted with a mailed questionnaire. Results: A total of 74 patients with first
AAP during the study period were included. Of these, 32% developed RAP during
follow-up. Of the patients, 72% received a documented BI during initial
hospitalization, with no difference between patients who later did or did not
develop RAP (71 vs. 72%; ns). Younger age (OR = 0.96, 95% CI = 0.92-1.00) and
higher AUDIT points (P = 0.044; OR = 5.6; 95% CI = 1.02-30.9 for >=20 AUDIT
points) were associated with RAP. AUDIT test had 70% sensitivity and 71%
specificity at a cut-off value of 20 points for predicting RAP. Conclusions: Only
72% of the patients received a documented BI during the initial hospitalization
for AAP. The in-hospital BI as such did not prevent the development of RAP. Young
patients with AUDIT points >=20 are especially at high risk for developing RAP
and should be included in a more intense follow-up care program to maximize
prevention. Short summary: During hospitalization for acute alcoholic
pancreatitis (AAP), one third of the patients did not receive brief interventions
(BIs). The in-hospital BI by itself was not sufficient enough to prevent disease
recurrence in follow-up of 4 years. Young age and higher AUDIT-points were
significant risk factors for recurrent attacks of AAP.
PMID- 28419180
TI - Impact of gestational nicotine exposure on intrauterine and fetal infection in a
rodent model.
AB - We investigated the interaction between prenatal nicotine exposure and
intrauterine infection using established rat models. Beginning at gestation day
(GD) 6, dams were continuously infused with either saline or 6 mg/kg/day nicotine
(Nic). At GD 14, dams received either sterile broth or 105 colony-forming units
Mycoplasma pulmonis (MP), resulting in four treatment groups: control (4 dams, 33
fetal units); MP only (5 dams, 55 fetal units); Nic only (5 dams, 61 fetal
units), and Nic + MP (7 dams, 82 fetal units). At GD 18, nicotine exposure
significantly increased (P <= 0.02) the percentage of amniotic fluids and fetuses
infected by MP but did not impact colonization rates of maternal sites. Nicotine
exposure significantly reduced the numbers of MP in the placenta required for
high microbial loads (>=104 color-changing units) in the amniotic fluid (P <
0.01). Fetal inflammatory response lesions were most extensive in the Nic only
and Nic + MP groups (P < 0.0001). Control and MP only placentas were interleukin
(IL)10-dominant, consistent with an M2/Th2 environment. Placentas exposed to
nicotine shifted to a neutral environment, with equivalent levels of interferon
gamma (IFNG) and IL10. Both IL6 and tumor necrosis factor (TNF) levels in
amniotic fluid were highly elevated when both nicotine and infection were
present. Our study suggests that prenatal exposure to nicotine increases the risk
for intrauterine infection, lowers the infectious dose required to breach the
placental barrier and infect the amniotic fluid and fetus, and alters the
pathology and inflammatory profile associated with maternal and fetal sites.
PMID- 28419181
TI - Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or
metastatic head and neck squamous cell carcinoma.
AB - Background: Pembrolizumab and nivolumab are immune checkpoint inhibitors
targeting PD-1 that have recently been approved in pretreated recurrent and/or
metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the
clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents
but rather to experience an acceleration of tumor growth kinetics (TGK). Patients
and methods: We retrospectively compared TGK on immunotherapy and TGK on last
treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four
French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before
treatment and the slope of tumor growth on treatment) was calculated.
Hyperprogression was defined as a TGKR >= 2. Results: From September 2012 to
September 2015, 34 patients were identified. Patterns of recurrence included
exclusive loco-regional recurrence in 14 patients, exclusive distant metastases
in 11 patients, and both in 9 patients. No pseudo-progression was observed.
Hyperprogression was observed in 10 patients (29%), including 9 patients with at
least a locoregional recurrence, and only 1 patient with exclusively distant
metastases. Hyperprogression significantly correlated with a regional recurrence
(TGKR >= 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant
recurrence. Hyperprogression was associated with a shorter progression-free
survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not
with overall survival (P = 0.77). Conclusions: Hyperprogression was observed in
29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated
with a shorter PFS. It occurred in 39% of patients with at least a locoregional
recurrence and 9% of patients with exclusively distant metastases. No pseudo
progressions were reported. Mechanisms and causality of hyperprogression should
further be assessed through prospective controlled studies.
PMID- 28419182
TI - Molecular classification of pulmonary sarcomatoid carcinomas suggests new
therapeutic opportunities.
AB - Background: Pulmonary sarcomatoid carcinoma (SC) is a rare disease with poor
prognosis and with strong inter- and intratumor heterogeneity. However, molecular
classification is currently focused on activating MET mutations. We sought to
better characterize the molecular diversity of SC using mutational signatures
that reflect different mutational processes, such as tobacco-associated adducts
(signature 4), BRCA1/BRCA2 deficiency (signature 3), or APOBEC enzyme deamination
(signatures 2 and 13). Patients and methods: Whole-exome sequencing was carried
out in 15 SC patients and on data from 10 previously published cases.
Hierarchical clustering and consensus non-negative matrix factorization were
carried out for samples classification based on mutational signatures. Results:
In the two series, SC distributed between two clusters (C): Csig4 (characterized
by signature 4) and Csig2-3-13 (signatures 2, 3, and 13). Csig4 exhibited more
frequent MAPK pathway mutations than Csig2-3-13 (pooled series: n = 10/14 versus
2/11, P < 0.05, respectively) and stronger PD-L1 expression (our series: n = 6/9
versus 1/6, P = 0.12). MET alterations were only found in Csig2-3-13 (pooled
series: n = 5/11 versus 0/14, P = 0.009), as well as BRCA1/BRCA2 (n = 3/11 versus
0/15), EGFR (n = 1), and IDH1 (n = 1) mutations. Csig2-3-13 patients had better
overall survival than Csig4 patients (median: >45 versus 7 months, respectively,
P = 0.001). Conclusions: Our study suggests that SC presents at least two
clusters comprising different mutational processes, gene alterations, and PD-L1
expression. New potential treatment possibilities are immune checkpoint
inhibitors in Csig4 and specific targeted agents in Csig2-3-13. These findings
should encourage clinicians to conduct broad molecular and immunological testing
in SC patients beyond MET exon 14 alterations.
PMID- 28419183
TI - Comparison of the Mutational Profiles of Primary Myelofibrosis, Polycythemia
Vera, and Essential Thrombocytosis.
AB - Objectives: To compare the mutational profiles of patients with primary
myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET).
Methods: Next-generation sequencing results of 75 cases of PMF, 33 cases of PV,
and 27 cases of ET were compared. Results: Mutation rates of ASXL1 and SRSF2 were
significantly higher in PMF than in PV or ET. ASXL1 mutations appeared to be more
frequently associated with risk of transformation to acute myeloid leukemia than
JAK2 or TET2 mutations. The most common mutation-cytogenetic combinations in
myeloproliferative neoplasm (MPN) were mutations of JAK2 or ASXL1 with del(20q)
and were more common in patients with PMF and PV than in patients with ET.
Differences were also found between patients with PMF and PV. Conclusions: PMF,
PV, and ET show different mutational profiles, which may be helpful in resolving
the differential diagnosis between MPNs. Due to the relatively small number of
cases and variable testing over time, larger controlled studies are necessary to
confirm the findings.
PMID- 28419184
TI - Mechanisms for the species difference between mouse and pig oocytes in their
sensitivity to glucorticoids.
AB - Although in vitro exposure to physiological concentrations of glucorticoids did
not affect maturation of mouse oocytes, it significantly inhibited nuclear
maturation of pig oocytes. Studies on this species difference in oocyte
sensitivity to glucocorticoids will contribute to our understanding of how
stress/glucocorticoids affect oocytes. We showed that glucorticoid receptors
(NR3C1) were expressed in both oocytes and cumulus cells (CCs) of both pigs and
mice; however, while cortisol inhibition of oocyte maturation was overcome by
NR3C1 inhibitor RU486 in pigs, it could not be relieved by RU486 in mice. The
mRNA level of 11beta-hydroxysteroid dehydrogenase 1 (HSD11B1) was significantly
higher than that of HSD11B2 in pig cumulus-oocyte complexes (COCs), whereas
HSD11B2 was exclusively expressed in mouse COCs. Pig and mouse cumulus-denuded
oocytes (DOs) expressed HSD11B2 predominantly and exclusively, respectively. In
the presence of cortisol, although inhibiting HSD11B2 decreased maturation rates
of COCs in both species, inhibiting HSD11B1 improved maturation of pig COCs while
having no effect on mouse COCs. Cortisol-cortisone interconversion observation
confirmed high HSD11B1 activities in pig oocytes but none in mouse oocytes, a
higher HSD11B2 activity in mouse than in pig oocytes, and a rapid cortisol
cortisone interconversion in pig COCs catalyzed by HSD11B1 from CCs and HSD11B2
from DOs. In conclusion, the species difference in glucocorticoid sensitivity
between pig and mouse oocytes is caused by their different contents/ratios of
HSD11B1 and HSD11B2, which maintain different concentrations of active
glucocorticoids. While cortisol inhibited pig oocytes by interacting with NR3C1,
glucocorticoid suppression of mouse oocytes was apparently not mediated by NR3C1.
PMID- 28419185
TI - A New Automated Technology for Cerebrospinal Fluid Cell Counts: Comparison of
Accuracy and Clinical Impact of GloCyte, Sysmex XN, and Manual Methods.
AB - Objectives: The purpose of the study was to compare the performance of GloCyte
(Advanced Instruments, Norwood, MA), a new semiautomated instrument for
cerebrospinal fluid cell counting, with the manual hemocytometer method and the
automated Sysmex XN (Sysmex, Kobe, Japan) body fluid mode. The clinical impact of
replacing the manual method with either automated method was determined. Methods:
Fifty-seven samples from 38 patients were analyzed by all three methods. Pearson
correlation and Passing-Bablok regression were used to compare methods. Cytospin
smears were reviewed on all samples, and clinical histories were obtained.
Results: There was a strong linear relationship between the manual and automated
methods for WBC counts ( R = 0.988 for GloCyte; R = 0.980 for Sysmex XN).
Positive bias was absent or negligible for WBC counts less than 30/MUL. GloCyte
and manual RBC counts were equivalent. There were no samples for which
replacement of manual WBC counts by automated counts would have changed the
diagnosis. Both automated methods showed improved precision for WBC counts
compared with the manual method. Conclusions: Replacing manual WBC counts by
GloCyte or Sysmex XN WBC counts would improve consistency of results without
compromising diagnostic accuracy.
PMID- 28419186
TI - CD4-Negative Variant of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm
With a Novel PBRM1 Mutation in an 11-Year-Old Girl.
AB - Objectives: We report a rare case of CD4- cutaneous blastic plasmacytoid
dendritic cell neoplasm (BPDCN) with a novel PBRM1 mutation. Methods: An 11-year
old girl presented with an enlarged mass on her left arm and underwent an
incisional biopsy. Results: Histopathologic examination and immunohistochemistry
studies showed a monotonous proliferation of blasts that were CD4-, CD56+, and
CD123+. There was no evidence of leukemic dissemination. Next-generation
sequencing detected PBRM1 and CIC gene abnormalities. We confirmed and validated
a novel PBRM1 mutation by conventional polymerase chain reaction and Sanger
sequencing. Conclusions: CD4- variant of BPDCN may be mistaken for myeloid
sarcoma or extramedullary lymphoblastic leukemia/lymphoma because of their
overlapping morphologic and immunophenotypic features; thus, a careful
clinicopathologic evaluation is essential to reach the correct diagnosis. PBRM1
mutation seems to be a driver event in this case. Our study underscores the
importance of alterations in chromatin remodeling in the pathogenesis of BPDCN.
PMID- 28419187
TI - Kaposi sarcoma in a patient treated with ruxolitinib.
PMID- 28419188
TI - Interactive Book Reading to Accelerate Word Learning by Kindergarten Children
With Specific Language Impairment: Identifying Adequate Progress and Successful
Learning Patterns.
AB - Purpose: The goal of this study was to provide guidance to clinicians on early
benchmarks of successful word learning in an interactive book reading treatment
and to examine how encoding and memory evolution during treatment contribute to
word learning outcomes by kindergarten children with specific language impairment
(SLI). Method: Twenty-seven kindergarten children with SLI participated in a
preliminary clinical trial using interactive book reading to teach 30 new words.
Word learning was assessed at 4 points during treatment through a picture naming
test. Results: The results indicate that the following performance during
treatment was cause for concern, indicating a need to modify the treatment:
naming 0-1 treated words correctly at Naming Test 1; naming 0-2 treated words
correctly at Naming Test 2; naming 0-3 treated words correctly at Naming Test 3.
In addition, the results showed that encoding was the primary limiting factor in
word learning, but rmemory evolution also contributed (albeit to a lesser degree)
to word learning success. Conclusion: Case illustrations demonstrate how a
clinician's understanding of a child's word learning strengths and weaknesses
develop over the course of treatment, substantiating the importance of regular
data collection and clinical decision-making to ensure the best possible outcomes
for each individual child.
PMID- 28419190
TI - Chainy: an universal tool for standardized relative quantification in real-time
PCR.
PMID- 28419189
TI - Propensity scores with misclassified treatment assignment: a likelihood-based
adjustment.
AB - Propensity score methods are widely used in comparative effectiveness research
using claims data. In this context, the inaccuracy of procedural or billing codes
in claims data frequently misclassifies patients into treatment groups, that is,
the treatment assignment ($T$) is often measured with error. In the context of a
validation data where treatment assignment is accurate, we show that
misclassification of treatment assignment can impact three distinct stages of a
propensity score analysis: (i) propensity score estimation; (ii) propensity score
implementation; and (iii) outcome analysis conducted conditional on the estimated
propensity score and its implementation. We examine how the error in $T$ impacts
each stage in the context of three common propensity score implementations:
subclassification, matching, and inverse probability of treatment weighting
(IPTW). Using validation data, we propose a two-step likelihood-based approach
which fully adjusts for treatment misclassification bias under subclassification.
This approach relies on two common measurement error-assumptions; non
differential measurement error and transportability of the measurement error
model. We use simulation studies to assess the performance of the adjustment
under subclassification, and also investigate the method's performance under
matching or IPTW. We apply the methods to Medicare Part A hospital claims data to
estimate the effect of resection versus biopsy on 1-year mortality among
$10?,284$ Medicare beneficiaries diagnosed with brain tumors. The ICD9 billing
codes from Medicare Part A inaccurately reflect surgical treatment, but SEER
Medicare validation data are available with more accurate information.
PMID- 28419191
TI - PPARdelta promotes tumor progression via activation of Glut1 and SLC1-A5
transcription.
AB - Malignant cancer cell uncontrolled growth depends on the persistent nutrient
availability such as glucose and amino acids, which is required for cancer cell
energetic and biosynthetic pathways. As a nuclear hormone receptor, peroxisome
proliferator-activated receptor delta (PPARdelta) plays a critical role in
inflammation and cancer, however, it is still unclear the regulatory mechanism of
PPARdelta on cancer cell metabolism. Here, we found that PPARdelta directly
regulated neutral amino acid transporter SLC1-A5 (solute carrier family 1 member
5) and glucose transporter-1 (Glut1) gene transcription, leading to uptake of
glucose and amino acid, activation of mTOR signaling, and tumor progression. In
contrast, silence of PPARdelta or its antagonist inhibited this event. More
importantly, PPARdelta promoted cancer cell metabolic reprogramming resulting in
chemoresistance, which was alleviated by PPARdelta antagonist. These findings
revealed a novel mechanism of PPARdelta-mediated tumor progression, which
provided a potential strategy for cancer treatment.
PMID- 28419192
TI - Efficacy and safety of a novel acetylcholinesterase inhibitor
octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II
multicenter randomised controlled trial.
AB - Background: inhibition of acetylcholinesterase (AChE) has been a effective
treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE
inhibitor, is a potential treatment for AD. Method: we conducted a multicenter,
randomised, double blind, placebo-controlled, parallel-group Phase II clinical
trial to investigate the effects of octohydroaminoacridine in patients with mild
to-moderate AD. Patients were randomised to receive placebo thrice daily,
octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle
dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose
group were titrated over 2-4 weeks. Changes from baseline to Week 16 were
assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's
Interview-Based Impression of Change Plus (CIBIC+), activities of daily living
(ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end
point of the study. A two-way analysis of covariance and least squares mean t
test were used. Results: at Week 16, the changes from baseline in ADAS-cog were
1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups,
respectively. Patients in the high-dose group had better performance in CIBIC+
and ADL scores at the end of the study. There was no significant difference in
the change in NPI score among the groups. The effects of octohydroaminoacridine
were dose dependent, and were effective within 16 weeks of treatment. No evidence
was found for more adverse events that occurred in different drug groups than
placebo group. Conclusions: octohydroaminoacridine significantly improved
cognitive function and behaviour in patients with mild-to-moderate AD and this
effect was dose dependent.
PMID- 28419193
TI - A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or
locally advanced transitional cell carcinoma of the urothelium (SECAVIN).
AB - Background: Despite the advent of immunotherapy in urothelial cancer, there is
still a need to find effective cytotoxic agents beyond first and second lines.
Vinflunine is the only treatment approved in this setting by the European
Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is
a taxane with activity in docetaxel-refractory cancers. A randomized study was
conducted to compare its efficacy versus vinflunine. Patients and methods: This
is a multicenter, randomized, open-label, phase II/III study, following a Simon's
optimal method with stopping rules based on an interim futility analysis and a
formal efficacy analysis at the end of the phase II. ECOG Performance Status,
anaemia and liver metastases were stratification factors. Primary objectives were
overall response rate for the phase II and overall survival for the phase III.
Results: Seventy patients were included in the phase II across 19 institutions in
Europe. Baseline characteristics were well balanced between the two arms. Three
patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and
six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression
free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P =
0.039). The study did not proceed to phase III since the futility analysis showed
a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found
favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related
adverse events were seen in 41% patients with no difference between the two arms.
Conclusion: This phase II/III second line bladder study comparing cabazitaxel
with vinflunine was closed when the phase II showed a lack of efficacy of the
cabazitaxel arm. Vinflunine results were consistent with those known previously.
Trial number: NCT01830231.
PMID- 28419194
TI - DMINDA 2.0: integrated and systematic views of regulatory DNA motif
identification and analyses.
AB - Motivation: Motif identification and analyses are important and have been long
standing computational problems in bioinformatics. Substantial efforts have been
made in this field during the past several decades. However, the lack of
intuitive and integrative web servers impedes the progress of making effective
use of emerging algorithms and tools. Results: Here we present an integrated web
server, DMINDA 2.0, which contains: (i) five motif prediction and analyses
algorithms, including a phylogenetic footprinting framework; (ii) 2125 species
with complete genomes to support the above five functions, covering animals,
plants and bacteria and (iii) bacterial regulon prediction and visualization.
Availability and Implementation: DMINDA 2.0 is freely available at
http://bmbl.sdstate.edu/DMINDA2. Contact: qin.ma@sdstate.edu. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 28419196
TI - The Need for Outcome Studies Prior to Large-Scale Implementation of Screening for
Anal Cancer.
PMID- 28419195
TI - Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of
metastatic colorectal cancer patients.
AB - Background: RAS assessment is mandatory for therapy decision in metastatic
colorectal cancer (mCRC) patients. This determination is based on tumor tissue,
however, genotyping of circulating tumor (ct)DNA offers clear advantages as a
minimally invasive method that represents tumor heterogeneity. Our study aims to
evaluate the use of ctDNA as an alternative for determining baseline RAS status
and subsequent monitoring of RAS mutations during therapy as a component of
routine clinical practice. Patients and methods: RAS mutational status in plasma
was evaluated in mCRC patients by OncoBEAMTM RAS CRC assay. Concordance of
results in plasma and tissue was retrospectively evaluated. RAS mutations were
also prospectively monitored in longitudinal plasma samples from selected
patients. Results: Analysis of RAS in tissue and plasma samples from 115 mCRC
patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were
mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico
pathological features showed that the site of metastasis (i.e. peritoneal, lung),
the histology of the tumor (i.e. mucinous) and administration of treatment
previous to blood collection negatively impacted the detection of RAS in ctDNA.
In patients with baseline mutant RAS tumors treated with
chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response
to treatment, being an early predictor of response. In patients RAS wt,
longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect
emergence of RAS mutations during anti-EGFR treatment. Conclusion: The high
overall agreement in RAS mutational assessment between plasma and tissue supports
blood-based testing with OncoBEAMTM as a viable alternative for genotyping RAS of
mCRC patients in routine clinical practice. Our study describes practical clinico
pathological specifications to optimize RAS ctDNA determination. Moreover,
OncoBEAMTM is useful to monitor RAS in patients undergoing systemic therapy to
detect resistance and evaluate the efficacy of particular treatments.
PMID- 28419197
TI - Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly
corrects metabolism and restores function in the diabetic heart following
hypoxia/reoxygenation.
AB - Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can
impair metabolic flexibility and function. Increased sarcolemmal fatty acid
translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium,
feeding increased fatty acid oxidation and elevated lipid deposition. Unlike
other metabolic modulators that target mitochondrial fatty acid oxidation, we
proposed that pharmacologically inhibiting fatty acid uptake, as the primary step
in the pathway, would provide an alternative mechanism to rebalance metabolism
and prevent lipid accumulation following hypoxic stress. Methods and results:
Hearts from type 2 diabetic and control male Wistar rats were perfused in
normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N
succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into
diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial
triglyceride concentration by 48% compared with untreated diabetic hearts,
restoring fatty acid metabolism to control levels following hypoxia
reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic
hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and
decreased lactate efflux rate by 56% compared with untreated diabetic hearts
during reoxygenation. In addition, SSO treatment of diabetic hearts increased
intermediates within the second span of the Krebs cycle, namely fumarate,
oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts
following decreased oxygen availability was prevented by SSO-infusion prior to
the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure
product by 60% during hypoxia and by 32% following reoxygenation, restoring
function to control levels. Conclusions: Diabetic hearts have limited metabolic
flexibility and cardiac dysfunction when stressed, which can be rapidly rectified
by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel
therapeutic approach not only reduces fat oxidation but also lipotoxicity, by
targeting the primary step in the fatty acid metabolism pathway.
PMID- 28419199
TI - Should We Revisit the Nephrotoxic Potential of Piperacillin-Tazobactam as Well?
PMID- 28419198
TI - Increased Syphilis Testing of Men Who Have Sex With Men: Greater Detection of
Asymptomatic Early Syphilis and Relative Reduction in Secondary Syphilis.
AB - Background: Syphilis rates have increased markedly among men who have sex with
men (MSM) internationally. We examined trends in syphilis testing and detection
of early syphilis among MSM in Australia. Methods: Serial cross-sectional
analyses on syphilis testing and diagnoses among MSM attending a national
sentinel network of 46 clinics in Australia between 2007 and 2014. Results:
359313 clinic visits were included. The proportion of MSM serologically tested
for syphilis annually increased in HIV-negative (48% to 91%; Ptrend < .0001) and
HIV-positive MSM (42% to 77%; Ptrend < .0001). The mean number of tests per man
per year increased from 1.3 to 1.6 in HIV-negative MSM (Ptrend < .0001) and from
1.6 to 2.3 in HIV-positive MSM (Ptrend < .0001). 2799 and 1032 syphilis cases
were detected in HIV-negative and HIV-positive MSM, respectively. Among HIV
negative MSM, the proportion of infections that were early latent increased from
27% to 44% (Ptrend < .0001), while the proportion that were secondary decreased
from 24% to 19% (Ptrend = .030). Among HIV-positive MSM, early latent infections
increased from 23% to 45% (Ptrend < .0001), while secondary infections decreased
from 45% to 26% (Ptrend = .0003). Among HIV-positive MSM, decreasing secondary
syphilis correlated with increasing testing coverage (r = -0.87; P = .005) or
frequency (r = -0.93; P = .001). Conclusions: Increases in syphilis screening
were associated with increased detection of asymptomatic infectious syphilis and
relative falls in secondary syphilis for both HIV-positive and HIV-negative MSM
nationally, suggesting interruption of syphilis progression.
PMID- 28419200
TI - Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human
Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term
Outcomes of a Randomized Trial.
AB - Background: We previously demonstrated the noninferiority of switching to
efavirenz (EFV) versus remaining on ritonavir-boosted lopinavir (LPV/r) for
virologic control in children infected with human immunodeficiency virus (HIV)
and exposed to nevirapine (NVP) for prevention of mother-to-child transmission.
Here we assess outcomes up to 4 years post-randomization. Methods: From 2010
2013, 298 NVP-exposed HIV-infected children >=3 years of age were randomized to
switch to EFV or remain on LPV/r in Johannesburg, South Africa
(Clinicaltrials.gov NCT01146873). After trial completion, participants were
invited to enroll into observational follow-up. We compared HIV RNA levels, CD4
counts and percentages, lipids, and growth across groups through four years post
randomization. Results: HIV RNA levels 51-1000 copies/mL were less frequently
observed in the EFV group than the LPV/r group (odds ratio [OR] 0.67, 95%
confidence interval [CI]: 0.51-0.88, P = .004), as was HIV RNA >1000 copies/mL
(OR 0.52 95% CI: 0.28-0.98, P = .04). The probability of confirmed HIV RNA >1000
copies/mL by 48 months was 0.07 and 0.12 in the EFV and LPV/r groups,
respectively (P = .21). Children randomized to EFV had a reduced risk of elevated
total cholesterol (OR 0.45 95% CI: 0.27-0.75, P = .002) and a reduced risk of
abnormal triglycerides (OR 0.42, 95% CI 0.29-0.62, P < .001). Conclusions: Our
results indicate that the benefits of switching virologically suppressed NVP
exposed HIV-infected children >=3 years of age from LPV/r to EFV are sustained
long-term. This approach has several advantages, including improved palatability,
reduced metabolic toxicity, simplified cotreatment for tuberculosis, and
preservation of second line options. Clinical Trials Registration: NCT01146873.
PMID- 28419201
TI - Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How
do Lapses in Monkey Performance Affect Cross-Species Correspondences?
AB - The cross-species correspondences and differences in how attention modulates
brain responses in humans and animal models are poorly understood. We trained 2
monkeys to perform an audio-visual selective attention task during functional
magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one
modality while ignoring those in the other. Monkey fMRI identified regions
strongly modulated by auditory or visual attention. Surprisingly, auditory
attention-related modulations were much more restricted in monkeys than humans
performing the same tasks during fMRI. Further analyses ruled out trivial
explanations, suggesting that labile selective-attention performance was
associated with inhomogeneous modulations in wide cortical regions in the
monkeys. The findings provide initial insights into how audio-visual selective
attention modulates the primate brain, identify sources for "lost" attention
effects in monkeys, and carry implications for modeling the neurobiology of human
cognition with nonhuman animals.
PMID- 28419202
TI - Genomic Characterization of USA300 Methicillin-Resistant Staphylococcus aureus
(MRSA) to Evaluate Intraclass Transmission and Recurrence of Skin and Soft Tissue
Infection (SSTI) Among High-Risk Military Trainees.
AB - Background: Military trainees are at increased risk for methicillin-resistant
Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI). Whole genome
sequencing (WGS) can refine our understanding of MRSA transmission and
microevolution in congregate settings. Methods: We conducted a prospective case
control study of SSTI among US Army infantry trainees at Fort Benning, Georgia,
from July 2012 to December 2014. We identified clusters of USA300 MRSA SSTI
within select training classes and performed WGS on clinical isolates. We then
linked genomic, phylogenetic, epidemiologic, and clinical data in order to
evaluate intra- and interclass disease transmission. Furthermore, among cases of
recurrent MRSA SSTI, we evaluated the intrahost relatedness of infecting strains.
Results: Nine training classes with >=5 cases of USA300 MRSA SSTI were selected.
Eighty USA300 MRSA clinical isolates from 74 trainees, 6 (8.1%) of whom had
recurrent infection, were subjected to WGS. We identified 2719 single nucleotide
variants (SNVs). The overall median (range) SNV difference between isolates was
173 (1-339). Intraclass median SNV differences ranged from 23 to 245. Two
phylogenetic clusters were suggestive of interclass MRSA transmission. One of
these clusters stemmed from 2 classes that were separated by a 13-month period
but housed in the same barracks. Among trainees with recurrent MRSA SSTI, the
intrahost median SNV difference was 7.5 (1-48). Conclusions: Application of WGS
revealed intra- and interclass transmission of MRSA among military trainees. An
interclass cluster between 2 noncontemporaneous classes suggests a long-term
reservoir for MRSA in this setting.
PMID- 28419203
TI - Selective Cutoff Reporting in Studies of Diagnostic Test Accuracy: A Comparison
of Conventional and Individual-Patient-Data Meta-Analyses of the Patient Health
Questionnaire-9 Depression Screening Tool.
AB - In studies of diagnostic test accuracy, authors sometimes report results only for
a range of cutoff points around data-driven "optimal" cutoffs. We assessed
selective cutoff reporting in studies of the diagnostic accuracy of the Patient
Health Questionnaire-9 (PHQ-9) depression screening tool. We compared
conventional meta-analysis of published results only with individual-patient-data
meta-analysis of results derived from all cutoff points, using data from 13 of 16
studies published during 2004-2009 that were included in a published conventional
meta-analysis. For the "standard" PHQ-9 cutoff of 10, accuracy results had been
published by 11 of the studies. For all other relevant cutoffs, 3-6 studies
published accuracy results. For all cutoffs examined, specificity estimates in
conventional and individual-patient-data meta-analyses were within 1% of each
other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%
15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the
standard cutoff, authors tended to report results for lower cutoffs that yielded
optimal results. When the PHQ-9 was highly sensitive, authors more often reported
results for higher cutoffs. Consequently, in the conventional meta-analysis,
sensitivity increased as cutoff severity increased across part of the cutoff
range-an impossibility if all data are analyzed. In sum, selective reporting by
primary study authors of only results from cutoffs that perform well in their
study can bias accuracy estimates in meta-analyses of published results.
PMID- 28419205
TI - Comparison of clinical features and survival between thymic carcinoma and thymic
carcinoid patients.
AB - OBJECTIVES: Thymic carcinoma (TC) and thymic carcinoid (TCD) are aggressive
thymic epithelial neoplasms with a poor prognosis. Due to rarity, little is known
about their comparative clinical characteristics, treatment outcomes and patterns
of relapse. METHODS: A retrospective cohort study was performed on 287 patients
with TC and 56 patients with TCD who were treated at the Shanghai Chest Hospital
between February 2003 and April 2014. Patient demographics, tumour stage,
treatment, pathologic findings and postoperative outcomes were compared between
the two tumour types using both multivariable Cox regression analysis and
propensity-matched analysis. RESULTS: Compared to patients with TC, significantly
more patients with TCD were male, had larger tumours, and displayed a greater
proportion of lymph node metastases. However, overall survival was similar (60.7%
5-year survival for TC, 80.7% for TCD, P = 0.159), as was disease-free survival
(41.1% 5-year survival for TC, 37.6% for TCD, P = 0.696) and patterns of
relapse. Multiple Cox regression analysis identified younger patients [hazard
ratio (HR) 1.018; 95% confidence interval (CI) 1.000-1.035; P = 0.047], more
completeness of resection (HR 1.424; 95% CI 1.105-1.836; P = 0.006), adjuvant
radiotherapy (HR 0.455; 95% CI 0.276-0.751; P = 0.002), and no adjuvant
chemotherapy (HR 1.799; 95% CI 1.017-3.183; P = 0.044) as independent factors
predicting better overall survival. Completeness of resection (HR 1.258; 95% CI
1.022-1.548; P = 0.031) and TNM stage (HR 1.479; 95% CI 1.107-1.977; P = 0.008)
were independent predictors of disease-free survival. Propensity matching
produced 46 patients in each group and no significant difference on overall
survival or disease-free survival was found. CONCLUSIONS: Patients with TCD have
discrete features but share a similar clinical course to those with TC. The
importance of complete resection in both of these thymic malignancies is
emphasized. Further investigation at multiple centers with the longer follow-up
data is required to substantiate our conclusion.
PMID- 28419204
TI - Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes
Multiple Individual Wild and Vaccine-Derived Polioviruses.
AB - Background: A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is
the rational option for completely eradicating poliovirus transmission. The
neutralizing capacity of Sabin-IPV immune serum to different strains of
poliovirus is a key indicator of the clinical protective efficacy of this
vaccine. Methods: Sera collected from 500 infants enrolled in a randomized,
blinded, positive control, phase 2 clinical trial were randomly divided into 5
groups: Groups A, B, and C received high, medium, and low doses, respectively, of
Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk
strain-based IPV, respectively, all on the same schedule. Immune sera were
collected after the third dose of primary immunization, and tested in cross
neutralization assays against 19 poliovirus strains of all 3 types. Results: All
immune sera from all 5 groups interacted with the 19 poliovirus strains with
various titers and in a dose-dependent manner. One type 2 immunodeficiency
associated vaccine-derived poliovirus strain was not recognized by these immune
sera. Conclusions: Sabin-IPV vaccine can induce protective antibodies against
currently circulating and reference wild poliovirus strains and most vaccine
derived poliovirus strains, with rare exceptions. Clinical Trials Registration:
NCT01056705.
PMID- 28419206
TI - Short-term preoperative exercise therapy does not improve long-term outcome after
lung cancer surgery: a randomized controlled study.
AB - OBJECTIVES: Poor aerobic fitness is a potential modifiable risk factor for long
term survival and quality of life in patients with lung cancer. This randomized
trial evaluates the impact of adding rehabilitation (Rehab) with high-intensity
interval training (HIIT) before lung cancer surgery to enhance cardiorespiratory
fitness and improve long-term postoperative outcome. METHODS: Patients with
operable lung cancer were randomly assigned to usual care (UC, n = 77) or to
intervention group (Rehab, n = 74) that entailed HIIT that was implemented only
preoperatively. Cardiopulmonary exercise testing (CPET) and pulmonary functional
tests (PFTs) including forced vital capacity (FVC), forced expiratory volume (FEV
1 ) and carbon monoxide transfer factor (KCO) were performed before and 1 year
after surgery. RESULTS: During the preoperative waiting time (median 25 days),
Rehab patients participated to a median of 8 HIIT sessions (interquartile [IQ] 25
75%, 7-10). At 1 year follow-up, 91% UC patients and 93% Rehab patients were
still alive ( P = 0.506). Pulmonary functional changes were non-significant and
comparable in both groups (FEV 1 mean -7.5%, 95% CI, -3.6 to -12.9 and in KCO
mean 5.8% 95% CI 0.8-11.8) Compared with preoperative CPET results, both groups
demonstrated similar reduction in peak oxygen uptake (mean -12.2% 95% CI -4.8 to
18.2) and in peak work rate (mean -11.1% 95% CI -4.2 to -17.4). CONCLUSIONS:
Short-term preoperative rehabilitation with HIIT does not improve pulmonary
function and aerobic capacity measured at 1 year after lung cancer resection.
TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01258478; www.clinicaltrials.gov .
PMID- 28419207
TI - CKII-SIRT1-SM22alpha loop evokes a self-limited inflammatory response in vascular
smooth muscle cells.
AB - Aims: Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-kappaB) activity in
response to the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha).
Smooth muscle (SM) 22alpha is a phosphorylation-regulated suppressor of IKK
IkappaBalpha-NF-kappaB signalling cascades in vascular smooth muscle cells
(VSMCs). Sm22alpha knockout results in increased expression of pro-inflammatory
genes in the aortas which are controlled by NF-kappaB. This study aimed to
investigate the relationship between SM22alpha and SIRT1 in the control of
vascular inflammation. Methods and results: The ligation injury model of Sirt1
Tg/Sm22alpha-/- mice displayed an increased level of the inflammatory molecules
in the carotid arteries compared with Sirt1-Tg mice, accompanied with aggravating
neointimal hyperplasia. In the in vitro study, on the one hand, we showed that
TNF-alpha induced the epigenetic silencing of SM22alpha transcription via EZH2
mediated H3K27 methylation in the SM22alpha promoter region, contributing to
inflammatory response. On the other hand, TNF-alpha simultaneously induced SIRT1
phosphorylation via CKII and thereby protected against inflammation.
Phosphorylated SIRT1 interacted with and deacetylated EZH2 and, subsequently,
promoted SM22alpha transcription by inhibiting EZH2 activity. Increased SM22alpha
in turn facilitated the phosphorylation and activation of SIRT1 via recruitment
of CKII to SIRT1, which amplified the anti-inflammatory effect of SIRT1.
Conclusion: Our findings demonstrate that, in response to TNF-alpha stimulation,
CKII-SIRT1-SM22alpha acts in a loop to reinforce the expression of SM22alpha,
which limits the inflammatory response in VSMCs in vivo and in vitro. The anti
inflammatory effect of SIRT1 may be dependent on SM22alpha to some extent. Our
data point to targeted activation of SIRT1 in VSMCs as a promising therapeutic
avenue in preventing cardiovascular diseases.
PMID- 28419208
TI - Interhemispheric Synchrony of Spontaneous Cortical States at the Cortical Column
Level.
AB - In cat early visual cortex, neural activity patterns resembling evoked
orientation maps emerge spontaneously under anesthesia. To test if such patterns
are synchronized between hemispheres, we performed bilateral imaging in
anesthetized cats using a new improved voltage-sensitive dye. We observed map
like activity patterns spanning early visual cortex in both hemispheres
simultaneously. Patterns virtually identical to maps associated with the cardinal
and oblique orientations emerged as leading principal components of the
spontaneous fluctuations, and the strength of transient orientation states was
correlated with their duration, providing evidence that these maps are
transiently attracting states. A neural mass model we developed reproduced the
dynamics of both smooth and abrupt orientation state transitions observed
experimentally. The model suggests that map-like activity arises from slow
modulations in spontaneous firing in conjunction with interplay between
excitation and inhibition. Our results highlight the efficiency and functional
precision of interhemispheric connectivity.
PMID- 28419209
TI - Estrogen Deficiency Exacerbates Type 1 Diabetes-Induced Bone TNF-alpha Expression
and Osteoporosis in Female Mice.
AB - Estrogen deficiency after menopause is associated with rapid bone loss,
osteoporosis, and increased fracture risk. Type 1 diabetes (T1D), characterized
by hypoinsulinemia and hyperglycemia, is also associated with bone loss and
increased fracture risk. With better treatment options, T1D patients are living
longer; therefore, the number of patients having both T1D and estrogen deficiency
is increasing. Little is known about the mechanistic impact of T1D in conjunction
with estrogen deficiency on bone physiology and density. To investigate this, 11
week-old mice were ovariectomized (OVX), and T1D was induced by multiple low-dose
streptozotocin injection. Microcomputed tomographic analysis indicated a marked
reduction in trabecular bone volume fraction (BVF) in T1D-OVX mice (~82%) that
was far greater than the reductions (~50%) in BVF in either the OVX and T1D
groups. Osteoblast markers, number, and activity were significantly decreased in
T1D-OVX mice, to a greater extent than either T1D or OVX mice. Correspondingly,
marrow adiposity was significantly increased in T1D-OVX mouse bone. Bone
expression analyses revealed that tumor necrosis factor (TNF)-alpha levels were
highest in T1D-OVX mice and correlated with bone loss, and osteoblast and
osteocyte death. In vitro studies indicate that estrogen deficiency and high
glucose enhance TNF-alpha expression in response to inflammatory signals. Taken
together, T1D combined with estrogen deficiency has a major effect on bone
inflammation, which contributes to suppressed bone formation and osteoporosis.
Understanding the mechanisms/effects of estrogen deficiency in the presence of
T1D on bone health is essential for fracture prevention in this patient
population.
PMID- 28419210
TI - Dasatinib Use and Risk of Cytomegalovirus Reactivation After Allogeneic
Hematopoietic-Cell Transplantation.
AB - Viral infections have been reported with dasatinib use, but its cytomegalovirus
risk after hematopoietic-cell transplantation (HCT) is not known. We found that
post-HCT dasatinib use increased the risk of cytomegalovirus reactivation
(adjusted hazard ratio, 7.65; 95% confidence interval, 1.84-31.7), controlling
for acute graft-versus-host disease, in 109 patients with Philadelphia-chromosome
positive malignancies.
PMID- 28419212
TI - Pleurectomy-decortication in malignant pleural mesothelioma: are different
surgical techniques associated with different outcomes? Results from a
multicentre study.
AB - OBJECTIVES: The potential benefit of surgery for malignant pleural mesothelioma
(MPM), especially concerning pleurectomy/decortication (P/D), is unclear from the
literature. The aim of this study was to evaluate the outcome after multimodality
treatment of MPM involving different types of P/D and to analyse the prognostic
factors. METHODS: We reviewed 314 patients affected by MPM who were operated on
in 11 Italian centres from 1 January 2007 to 11 October 2014. RESULTS: The
characteristics of the population were male/female ratio: 3.7/1, and median age
at operation was 67.8 years. The epithelioid histotype was observed in 79.9% of
patients; neoadjuvant chemotherapy was given to 57% of patients and Stage III
disease was found following a pathological analysis in 62.3% of cases. A total of
162 (51.6%) patients underwent extended P/D (EP/D); 115 (36.6%) patients had P/D
and 37 (11.8%) received only a partial pleurectomy. Adjuvant radiotherapy was
delivered in 39.2% of patients. Median overall survival time after surgery was
23.0 [95% confidence interval (CI): 19.6-29.1] months. On multivariable (Cox)
analysis, pathological Stage III-IV [ P = 0.004, hazard ratio (HR):1.34; 95% CI:
1.09-1.64], EP/D and P/D ( P = 0.006, HR for EP/D: 0.46; 95% CI: 0.29-0.74; HR
for P/D: 0.52; 95% CI: 0.31-0.87), left-sided disease ( P = 0.01, HR: 1.52; 95%
CI: 1.09-2.12) and pathological status T4 ( P = 0.0003, HR: 1.38; 95% CI: 1.14
1.66) were found to be independent significant predictors of overall survival.
CONCLUSIONS: Whether the P/D is extended or not, it shows similarly good outcomes
in terms of early results and survival rate. In contrast, a partial pleurectomy,
which leaves gross tumour behind, has no impact on survival.
PMID- 28419211
TI - The Inhibitory G Protein alpha-Subunit, Galphaz, Promotes Type 1 Diabetes-Like
Pathophysiology in NOD Mice.
AB - The alpha-subunit of the heterotrimeric Gz protein, Galphaz, promotes beta-cell
death and inhibits beta-cell replication when pancreatic islets are challenged by
stressors. Thus, we hypothesized that loss of Galphaz protein would preserve
functional beta-cell mass in the nonobese diabetic (NOD) model, protecting from
overt diabetes. We saw that protection from diabetes was robust and durable up to
35 weeks of age in Galphaz knockout mice. By 17 weeks of age, Galphaz-null NOD
mice had significantly higher diabetes-free survival than wild-type littermates.
Islets from these mice had reduced markers of proinflammatory immune cell
infiltration on both the histological and transcript levels and secreted more
insulin in response to glucose. Further analyses of pancreas sections revealed
significantly fewer terminal deoxynucleotidyltransferase-mediated dUTP nick end
labeling (TUNEL)-positive beta-cells in Galphaz-null islets despite similar
immune infiltration in control mice. Islets from Galphaz-null mice also exhibited
a higher percentage of Ki-67-positive beta-cells, a measure of proliferation,
even in the presence of immune infiltration. Finally, beta-cell-specific Galphaz
null mice phenocopy whole-body Galphaz-null mice in their protection from
developing hyperglycemia after streptozotocin administration, supporting a beta
cell-centric role for Galphaz in diabetes pathophysiology. We propose that
Galphaz plays a key role in beta-cell signaling that becomes dysfunctional in the
type 1 diabetes setting, accelerating the death of beta-cells, which promotes
further accumulation of immune cells in the pancreatic islets, and inhibiting a
restorative proliferative response.
PMID- 28419214
TI - The Evidence That Increased Syphilis Testing Controls Syphilis Is Compelling:
What Is Needed to Act?
PMID- 28419213
TI - Risk Factors for Congenital Cytomegalovirus Infection Following Primary and
Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using
Polymerase Chain Reaction in Saliva.
AB - Background: The design of diagnostic and preventive strategies have been
prevented by gaps in knowledge of the epidemiology of congenital cytomegalovirus
(cCMV) with the type of maternal infection as well as the lack of large-scale
neonatal screening tools. Methods: In sum, 11715 consecutive newborns were
screened for cCMV by polymerase chain reaction (PCR) in saliva. Prevalence, type
of maternal infection, sociodemographic, obstetrical, and serological data were
analyzed. Results: Positive predictive value of CMV PCR in saliva was 59%; false
positive results were associated with lower viral loads (P < .001). Maternal
seroprevalence was 61%, birth prevalence was 0.37%, resulting from primary and
nonprimary infections in 52% and 47.7% of cases, respectively. The risk to
deliver an infected baby after primary infection was increased in younger (OD =
7.9), parous (OD = 4.1) women born in high resources countries (OD = 5.2) and
from higher income groups (P = .019). The only 2 risk factors to deliver an
infected baby after nonprimary infection were to be young (OD = 4.6) and
unemployed (OD = 5.8). The risk to deliver an infected baby was 4-fold higher in
women seronegative before their pregnancy (P = .021). Conclusions: A positive CMV
PCR in newborns' saliva should always be confirmed in a repeat-sample.
Sociodemographic characteristics of women giving birth to an infected baby after
primary and nonprimary infection are different. Seronegative, parous women
represent the highest risk population for cCMV in countries with low to
intermediate seroprevalence. Urgent action is needed to stop the cCMV's epidemic,
particularly in this population easily identifiable by maternal serology and
amenable to prevention messages. Clinical Trials Registration: NCT01923636.
PMID- 28419215
TI - Reply to Allan-Blitz and Klausner.
PMID- 28419217
TI - Shock efficacy of single and dual coil electrodes-new insights from the NORDIC
ICD Trial.
AB - Aims: Dual coil (DC) electrodes are preferred to single coil (SC) electrodes
because of an assumed higher shock efficacy. However, DC-electrodes may be
associated with an increased difficulty and risk of lead extraction. We aimed to
compare SC- and DC-electrodes with respect to the first shock efficacy (FSE)
after implantable cardioverter defibrillator (ICD) implantation. Methods and
results: One thousand and seventy-seven patients of the NORDIC ICD trial were
randomly assigned to first time ICD implantation with or without defibrillation
(DF) testing. The electrode configuration was determined before randomization.
One thousand and sixty-seven patients eventually received an ICD, 516 (48.4%)
with a SC- and 551 (51.6%) with a DC-electrode. DC-electrodes were preferentially
selected in older patients, renal failure, atrial fibrillation, dual chamber,
Cardiac Resynchronization Therapy (CRT) devices, angiotensin-converting-enzyme
(ACE) inhibitors/angiotensin (AT) receptor blockers and without Sotalol. However,
the preference of the investigational site was dominant over clinical parameters.
The DF energy at the final electrode position was higher in SC-electrodes
(adjusted difference +1.15 J; P = 0.005; only patients tested). Less patients
with DC-electrodes required intra-operative system reconfiguration (adjusted
difference -3.9; P = 0.046; only patients tested). Using mixed logistic
regression, the FSE was 92.6% in SC- and 97.8% in DC-electrodes (adjusted odds
ratio 4.3 (95% confidence interval [1.9, 9.8]; P < 0.001)). Conclusion: Dual coil
electrode selection mainly depends on the preference of the investigational site
and seems to be preferred in older patients, renal failure, atrial fibrillation,
dual chamber, and CRT devices. Patients with DC-electrodes required less
intraoperative system reconfigurations. Dual coil-electrodes provided a
substantially higher FSE during follow-up. Mortality rates were not significantly
different in patients with DC- and SC-electrodes.
PMID- 28419218
TI - Radiotherapy in a leadless pacemaker.
PMID- 28419216
TI - LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent
mechanism.
AB - Aims: Ageing is associated with impairment of endothelial nitric oxide synthase
(eNOS) and progressive reduction in endothelial function. A genetic study on long
living individuals-who are characterized by delays in ageing and in the onset of
cardiovascular disease-previously revealed I229V (rs2070325) in
bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4)
as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO
production and vasorelaxation through a protein kinase R-like endoplasmic
reticulum kinase/14-3-3/heat shock protein 90 signal. Here, we further
characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement
of vascular function. Methods and results: LAV-BPIFB4 upregulated eNOS function
via mobilization of Ca2+ and activation of protein kinase C alpha (PKCalpha).
Indeed, the overexpression of LAV-BPIFB4 in human endothelial cells enhanced ATP
induced Ca2+ mobilization and the translocation of PKCalpha to the plasma
membrane. Coherently, pharmacological inhibition of PKCalpha blunted the positive
effect of LAV-BPIFB4 on eNOS and endothelial function. In addition, although LAV
BPIFB4 lost the ability to activate PKCalpha and eNOS in ex vivo vessels studied
in an external Ca2+-free medium and in vessels from eNOS-/- mice, it still
potentiated endothelial activity, recruiting an alternative mechanism dependent
upon endothelium-derived hyperpolarizing factor (EDHF). Conclusions: We have
identified novel molecular determinants of the beneficial effects of LAV-BPIFB4
on endothelial function, showing the roles of Ca2+ mobilization and PKCalpha in
eNOS activation and of EDHF when eNOS is inhibited. These results highlight the
role LAV-BPIFB4 can have in restoring signals that are lost during ageing.
PMID- 28419219
TI - DNA remodelling by Strict Partial Endoreplication in orchids, an original process
in the plant kingdom.
AB - DNA remodelling during endoreplication appears to be a strong developmental
characteristic in orchids. In this study, we analysed DNA content and nuclei in
41 species of orchids to further map the genome evolution in this plant family.
We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied
corresponds to strict partial endoreplication. Such process is developmentally
regulated in each wild species studied. Cytometry data analyses allowed us to
propose a model where nuclear states 2C, 4E, 8E, etc. form a series comprising a
fixed proportion, the euploid genome 2C, plus 2 to 32 additional copies of a
complementary part of the genome. The fixed proportion ranged from 89% of the
genome in Vanilla mexicana down to 19% in V. pompona, the lowest value for all
148 orchids reported. Insterspecific hybridisation did not suppress this
phenomenon. Interestingly, this process was not observed in mass-produced
epiphytes. Nucleolar volumes grow with the number of endocopies present, coherent
with high transcription activity in endoreplicated nuclei. Our analyses suggest
species-specific chromatin rearrangement. Towards understanding endoreplication,
V. planifolia constitutes a tractable system for isolating the genomic sequences
that confer an advantage via endoreplication from those that apparently suffice
at diploid level.
PMID- 28419221
TI - Should all individuals with a non-diagnostic electrocardiogram undergo ajmaline
challenge to unmask the concealed arrhythmic overlap syndromes?
PMID- 28419220
TI - Genome sequence and physiological analysis of Yamadazyma laniorum f.a. sp. nov.
and a reevaluation of the apocryphal xylose fermentation of its sister species,
Candida tenuis.
AB - Xylose fermentation is a rare trait that is immensely important to the cellulosic
biofuel industry, and Candida tenuis is one of the few yeasts that has been
reported with this trait. Here we report the isolation of two strains
representing a candidate sister species to C. tenuis. Integrated analysis of
genome sequence and physiology suggested the genetic basis of a number of traits,
including variation between the novel species and C. tenuis in lactose metabolism
due to the loss of genes encoding lactose permease and beta-galactosidase in the
former. Surprisingly, physiological characterization revealed that neither the
type strain of C. tenuis nor this novel species fermented xylose in traditional
assays. We reexamined three xylose-fermenting strains previously identified as C.
tenuis and found that these strains belong to the genus Scheffersomyces and are
not C. tenuis. We propose Yamadazyma laniorum f.a. sp. nov. to accommodate our
new strains and designate its type strain as yHMH7 (=CBS 14780 = NRRL Y-63967T).
Furthermore, we propose the transfer of Candida tenuis to the genus Yamadazyma as
Yamadazyma tenuis comb. nov. This approach provides a roadmap for how integrated
genome sequence and physiological analysis can yield insight into the mechanisms
that generate yeast biodiversity.
PMID- 28419222
TI - Reply to Manian.
PMID- 28419223
TI - Removal of batch effects using distribution-matching residual networks.
AB - Motivation: Sources of variability in experimentally derived data include
measurement error in addition to the physical phenomena of interest. This
measurement error is a combination of systematic components, originating from the
measuring instrument and random measurement errors. Several novel biological
technologies, such as mass cytometry and single-cell RNA-seq (scRNA-seq), are
plagued with systematic errors that may severely affect statistical analysis if
the data are not properly calibrated. Results: We propose a novel deep learning
approach for removing systematic batch effects. Our method is based on a residual
neural network, trained to minimize the Maximum Mean Discrepancy between the
multivariate distributions of two replicates, measured in different batches. We
apply our method to mass cytometry and scRNA-seq datasets, and demonstrate that
it effectively attenuates batch effects. Availability and Implementation: our
codes and data are publicly available at
https://github.com/ushaham/BatchEffectRemoval.git. Contact:
yuval.kluger@yale.edu. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 28419224
TI - Avoiding oesophageal injury during cardiac ablation: insights gained from
mediastinal anatomy.
AB - Aims: This study investigates the lateral displacement of the oesophagus at the
level of the left atrium (LA) in 11 cadavers. Methods and results: The study was
conducted using human cadavers. An endotracheal stylet probe was inserted into
the eosphagus. The pericardium overlying the posterior LA was fixed in place. The
lateral movement of the oesophagus from side to side was recorded. The initial
study method had the stylet probe extending to the gastroesophageal (GE)
junction. A revised protocol had the distal end of the endotracheal stylet probe
~4 cm cranial to the GE junction. In six cadavers using the initial study method,
the oesophagus was displaced a mean of 1.8 +/- 0.35 cm to the right and 2 +/-
0.48 cm to the left. In five cadavers, using the revised method, the oesophagus
was displaced by a mean of 2.26 +/- 0.27 cm to the right and 2.3 +/- 0.66 cm to
the left. Conclusion: Mediastinal anatomy, specifically the presence of a loose
connective tissue that attaches the oesophagus to the parietal pericardium
overlying the posterior LA wall will allow for a lateral displacement of the
oesophagus. This should decrease or eliminate the likelihood of thermal injury of
the oesophagus. Using an endotracheal stylet, we investigated the lateral
displacement of the oesophagus in 11 human cadavers. In six with the stylet
extending to the GE junction, the oesophagus was displaced a mean of 3.8 cm. In
five, with stylet 4 cm cranial to the junction, the displacement was 4.56 cm.
PMID- 28419225
TI - Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells.
AB - Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn
antigens (GalNAc-Ser/Thr) binding equally to three dimeric forms of the epitope,
Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of
G2-D11 is minimally influenced by the peptide structure, which indicates a high
degree of carbohydrate epitope dominance and a low influence from the protein
backbone. With a high affinity (KDapp = 1.3 * 10-8 M) and no cross-reactivity to
either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent
candidate for a well-defined anti-Tn-antigen reagent. Detailed
immunohistochemical evaluation of tissue sections from a cohort of 80 patients
with gastric carcinoma showed in all cases positive tumor cells. The observed
staining was localized to the cytoplasm and in some cases to the membrane,
whereas the surrounding tissue was completely negative demonstrating the
usefulness of the novel Tn-antigen binding antibody.
PMID- 28419226
TI - Sugar versus fat: elimination of glycogen storage improves lipid accumulation in
Yarrowia lipolytica.
AB - Triacylglycerol (TAG) and glycogen are the two major metabolites for carbon
storage in most eukaryotic organisms. We investigated the glycogen metabolism of
the oleaginous Y. lipolytica and found that this yeast accumulates up to 16%
glycogen in its biomass. Assuming that elimination of glycogen synthesis would
result in an improvement of lipid accumulation, we characterized and deleted the
single gene coding for glycogen synthase, YlGSY1. The mutant was grown under
lipogenic conditions with glucose and glycerol as substrates and we obtained up
to 60% improvement in TAG accumulation compared to the wild type strain.
Additionally, YlGSY1 was deleted in a background that was already engineered for
high lipid accumulation. In this obese background, TAG accumulation was also
further increased. The highest lipid content of 52% was found after 3 days of
cultivation in nitrogen-limited glycerol medium. Furthermore, we constructed
mutants of Y. lipolytica and S. cerevisiae that are deleted for both glycogen and
TAG synthesis, demonstrating that the ability to store carbon is not essential.
Overall, this work showed that glycogen synthesis is a competing pathway for TAG
accumulation in oleaginous yeasts and that deletion of the glycogen synthase has
beneficial effects on neutral lipid storage.
PMID- 28419228
TI - Native aortic valve thrombosis in patient with protein S deficiency.
AB - Native aortic valve thrombosis is an extremely rare condition, the causes of
which include previous aortic valve diseases, endocarditis, valvular injury by a
catheter intervention and an underlying hypercoagulative state. Its diagnosis is
important for preventing life-threatening embolic complications. Here, we report
a case of native aortic valve thrombosis and recurrent systemic embolism in a
patient with protein S deficiency, a disorder associated with a hypercoagulative
state.
PMID- 28419227
TI - Neural Programmatic Role of Leptin, TNFalpha, Melanocortin, and Glutamate in
Blood Pressure Regulation vs Obesity-Related Hypertension in Male C57BL/6 Mice.
AB - Continuous nutritional surplus sets the stage for hypertension development.
Whereas moderate dietary obesity in mice is normotensive, the homeostatic balance
is disrupted concurrent with an increased risk of hypertension. However, it
remains unclear how the obesity-associated prehypertensive state is converted
into overt hypertension. Here, using mice with high-fat-diet (HFD)-induced
moderate obesity vs control diet (CD)-fed lean mice, we comparatively studied the
effects of central leptin and tumor necrosis factor-alpha (TNFalpha) as well as
the involvement of the neuropeptide melanocortin pathway vs the neurotransmitter
glutamate pathway. Compared with CD-fed lean mice, the pressor effect of central
excess leptin and TNFalpha, but not melanocortin, was sensitized in HFD-fed mice.
The pressor effect of central leptin in HFD-fed mice was strongly suppressed by
glutamatergic inhibition but not by melanocortinergic inhibition. The pressor
effect of central TNFalpha was substantially reversed by melanocortinergic
inhibition in HFD-fed mice but barely in CD-fed mice. Regardless of diet, the
hypertensive effects of central TNFalpha and melanocortin were both partially
reversed by glutamatergic suppression. Hence, neural control of blood pressure is
mediated by a signaling network between leptin, TNFalpha, melanocortin, and
glutamate and changes in dynamics due to central excess leptin and TNFalpha
mediate the switch from normal physiology to obesity-related hypertension.
PMID- 28419229
TI - Non-invasive assessment of cerebral oxygen metabolism following surgery of
congenital heart disease.
AB - OBJECTIVES: Cerebral protection is a major issue in the treatment of infants with
complex congenital heart disease. We tested a new device combining tissue
spectrometry and laser Doppler flowmetry for non-invasive determination of
cerebral oxygen metabolism following cardiac surgery in infants. METHODS: We
prospectively measured regional cerebral oxygen saturation cSO 2 and
microperfusion (rcFlow) in 43 infants 12-24 h following corrective ( n = 30) or
palliative surgery ( n = 13) of congenital heart defects. For comparison,
cerebral blood flow (CBF) was determined by colour duplex sonography of the
extracranial cerebral arteries. Cerebral fractional tissue oxygen extraction,
approximated cerebral metabolic rate of oxygen (aCMRO 2 ) and cerebral metabolic
rate of oxygen (CMRO 2 ) were calculated. RESULTS: cSO 2 was lower [54.6% (35.7
64.0) vs 59.7% (44.5-81.7); P < 0.01] after neonatal palliation, while rcFlow
[69.7 AU (42.5-165.3) vs 77.0 AU (41.2-168.1); P = 0.06] and cerebral fractional
tissue oxygen extraction [0.34 (0.24-0.82) vs 0.38 (0.17-0.55); P = 0.63] showed
a trend towards lower values. We found a positive correlation between aCMRO 2 and
CMRO 2 ( r = 0.27; P = 0.03). aCMRO 2 was significantly lower after neonatal
palliation [4.0 AU (2.1-6.3) vs 4.9 AU (2.2-15.6); P = 0.02]. CONCLUSIONS:
According to our experience, combined photospectrometry and laser Doppler
flowmetry enable non-invasive assessment of cerebral oxygen metabolism. The
method promises new insights into perioperative cerebral perfusion following
palliation or corrective surgery in infancy.
PMID- 28419230
TI - Structuring (right) atrial fibrillation: location matters.
PMID- 28419231
TI - Antibiotic resistance in Staphylococcus aureus. Current status and future
prospects.
AB - The major targets for antibiotics in staphylococci are (i) the cell envelope,
(ii) the ribosome and (iii) nucleic acids. Several novel targets emerged from
recent targeted drug discovery programmes including the ClpP protease and FtsZ
from the cell division machinery. Resistance can either develop by horizontal
transfer of resistance determinants encoded by mobile genetic elements viz
plasmids, transposons and the staphylococcal cassette chromosome or by mutations
in chromosomal genes. Horizontally acquired resistance can occur by one of the
following mechanisms: (i) enzymatic drug modification and inactivation, (ii)
enzymatic modification of the drug binding site, (iii) drug efflux, (iv) bypass
mechanisms involving acquisition of a novel drug-resistant target, (v)
displacement of the drug to protect the target. Acquisition of resistance by
mutation can result from (i) alteration of the drug target that prevents the
inhibitor from binding, (ii) derepression of chromosomally encoded multidrug
resistance efflux pumps and (iii) multiple stepwise mutations that alter the
structure and composition of the cell wall and/or membrane to reduce drug access
to its target. This review focuses on development of resistance to currently used
antibiotics and examines future prospects for new antibiotics and informed use of
drug combinations.
PMID- 28419232
TI - Corrigendum: Time-discounting and tobacco smoking: a systematic review and
network analysis.
PMID- 28419233
TI - Epicardial ablation may not be necessary in all patients with arrhythmogenic
right ventricular dysplasia/cardiomyopathy and frequent ventricular tachycardia:
author's reply.
PMID- 28419234
TI - Copy number alterations assessed at the single-cell level revealed mono- and
polyclonal seeding patterns of distant metastasis in a small-cell lung cancer
patient.
PMID- 28419235
TI - A Bayesian group sparse multi-task regression model for imaging genetics.
AB - Motivation: Recent advances in technology for brain imaging and high-throughput
genotyping have motivated studies examining the influence of genetic variation on
brain structure. Wang et al. have developed an approach for the analysis of
imaging genomic studies using penalized multi-task regression with regularization
based on a novel group l2,1-norm penalty which encourages structured sparsity at
both the gene level and SNP level. While incorporating a number of useful
features, the proposed method only furnishes a point estimate of the regression
coefficients; techniques for conducting statistical inference are not provided. A
new Bayesian method is proposed here to overcome this limitation. Results: We
develop a Bayesian hierarchical modeling formulation where the posterior mode
corresponds to the estimator proposed by Wang et al. and an approach that allows
for full posterior inference including the construction of interval estimates for
the regression parameters. We show that the proposed hierarchical model can be
expressed as a three-level Gaussian scale mixture and this representation
facilitates the use of a Gibbs sampling algorithm for posterior simulation.
Simulation studies demonstrate that the interval estimates obtained using our
approach achieve adequate coverage probabilities that outperform those obtained
from the nonparametric bootstrap. Our proposed methodology is applied to the
analysis of neuroimaging and genetic data collected as part of the Alzheimer's
Disease Neuroimaging Initiative (ADNI), and this analysis of the ADNI cohort
demonstrates clearly the value added of incorporating interval estimation beyond
only point estimation when relating SNPs to brain imaging endophenotypes.
Availability and Implementation: Software and sample data is available as an R
package 'bgsmtr' that can be downloaded from The Comprehensive R Archive Network
(CRAN). Contact: nathoo@uvic.ca. Supplementary information: Supplementary data
are available at Bioinformatics online.
PMID- 28419236
TI - Studying the effect of administration route and treatment dose on the selection
of enrofloxacin resistance in commensal Escherichia coli in broilers.
AB - Objectives: Factors potentially contributing to fluoroquinolone resistance
selection in commensal Escherichia coli strains in poultry were studied through a
series of in vivo experiments. The effect of the initial prevalence of
enrofloxacin resistance in the E. coli gut microbiota, effect of the bacterial
fitness of the enrofloxacin-resistant strain and effect of treatment with
enrofloxacin (effect of dose and effect of route of administration) were
assessed. Methods: Four in vivo studies with broiler chickens were performed.
Right after hatching, the chicks were inoculated with either a bacteriologically
fit or a bacteriologically non-fit fluoroquinolone-resistant strain as either a
minority or the majority of the total E. coli population. Six days later, the
chicks were treated for three consecutive days either orally or parenterally and
using three different doses (under-, correct- and over-dose) of enrofloxacin. The
faecal shedding of E. coli strains was quantified by plating on agar plates
either supplemented or not supplemented with enrofloxacin. Linear mixed models
were used to assess the effect of the aforementioned variables on the selection
of enrofloxacin resistance. Results: The factors that significantly contributed
were treatment ( P < 0.001), bacterial fitness of the resistant donor strain (
P < 0.001), administration route ( P = 0.052) and interactions between
bacterial fitness and administration route ( P < 0.001). Conclusions: In the
currently used models, fluoroquinolone resistance selection was influenced by
treatment, bacterial fitness of the inoculation strain and administration route.
The use of oral treatment seems to select more for fluoroquinolone resistance,
particularly in the model where a non-fit strain was used for inoculation.
PMID- 28419238
TI - Antiretroviral Therapy Initiation and Changes in Self-Reported Depression.
AB - In this retrospective study of treatment-naive PLWH initiating antiretroviral
therapy, the score for the depression scale of the Patient Health Questionnaire
(PHQ-9) was significantly higher at baseline (median, 6.0; interquartile range, 2
11) than at 12 months (3.0; 0-8; P < .001). Baseline depression and lack of
insurance are associated with 12-month depression, but receipt of efavirenz-based
antiretroviral therapy is not.
PMID- 28419239
TI - Quantitative Analysis of Long-Term Mass Rearing of Neoseiulus californicus
(Acari: Phytoseiidae) on Almond Pollen.
AB - Long-term feeding effects of the almond pollen on the life table parameters of
Neoseiulus californicus McGregor were assessed after 5, 10, and 20 generations
after introduction in the rearing arena. Furthermore, to evaluate behavioral
characteristics of the mass-reared predator (strain A) in face with the real
prey, functional and numerical responses of the predator to different densities
of the twospotted spider mite nymphs were determined, and the obtained data were
compared with those reared on twospotted spider mite (strain T). Long-term
rearing did not significantly affect total fecundity of N. californicus (ranged
from 37.79 to 41.91 eggs). Nevertheless, preadult duration in the 5th generation
was significantly longer than the 10th and 20th generations. The intrinsic rate
of increase (r) in the 10th (0.2056 d-1) and 20th (0.2201 d-1) generations had
not significant difference together. However, the r value slightly dropped in the
5th generation (0.1706 d-1) because of the irregular offering of fresh pollen to
the rearing colonies before that. Both strains of N. californicus exhibited a
type II functional response; however, the N. californicus reared on the almond
pollen (strain A) had a higher attack rate (a) and shorter handling time (Th).
The individuals reared on the almond pollen had a greater size than those reared
on twospotted spider mite; its higher predation potential is probably due to this
characteristic. Consequently, the rearing of N. californicus on the almond pollen
positively affected its attributes including high survivorship, body size, and
fecundity, and subsequently higher potential to control twospotted spider mite.
PMID- 28419237
TI - The FAT Score, a Fibrosis Score of Adipose Tissue: Predicting Weight-Loss Outcome
After Gastric Bypass.
AB - Context: Bariatric surgery (BS) induces major and sustainable weight loss in many
patients. Factors predicting poor weight-loss response (PR) need to be identified
to improve patient care. Quantification of subcutaneous adipose tissue (scAT)
fibrosis is negatively associated with post-BS weight loss, but whether it could
constitute a predictor applicable in clinical routine remains to be demonstrated.
Objective: To create a semiquantitative score evaluating scAT fibrosis and test
its predictive value on weight-loss response after Roux-en-Y gastric bypass
(RYGB). Methods: We created a fibrosis score of adipose tissue (FAT score)
integrating perilobular and pericellular fibrosis. Using this score, we
characterized 183 perioperative scAT biopsy specimens from severely obese
patients who underwent RYGB (n = 85 from a training cohort; n = 98 from a
confirmation cohort). PR to RYGB was defined as <28% of total weight loss at 1
year (lowest tertile). The link between FAT score and PR was tested in univariate
and multivariate models. Results: FAT score was directly associated with
increasing scAT fibrosis measured by a standard quantification method (P for
trend <0.001). FAT score interobserver agreement was good (kappa = 0.76). FAT
score >=2 was significantly associated with PR. The association remained
significant after adjustment for age, diabetes status, hypertension, percent fat
mass, and interleukin-6 level (adjusted odds ratio, 3.6; 95% confidence interval,
1.8 to 7.2; P = 0.003). Conclusion: The FAT score is a new, simple,
semiquantitative evaluation of human scAT fibrosis that may help identify
patients with a potential limited weight-loss response to RYGB.
PMID- 28419240
TI - From Nano to Micro: using nanotechnology to combat microorganisms and their
multidrug resistance.
AB - The spread of antibiotic resistance and increasing prevalence of biofilm
associated infections is driving demand for new means to treat bacterial
infection. Nanotechnology provides an innovative platform for addressing this
challenge, with potential to manage even infections involving multidrug-resistant
(MDR) bacteria. The current review summarizes recent progress over the last 2
years in the field of antibacterial nanodrugs, and describes their unique
properties, mode of action and activity against MDR bacteria and biofilms.
Biocompatibility and commercialization are also discussed. As opposed to the more
common division of nanoparticles (NPs) into organic- and inorganic-based
materials, this review classifies NPs into two functional categories. The first
includes NPs exhibiting intrinsic antibacterial properties and the second is
devoted to NPs serving as a cargo for delivering antibacterial agents.
Antibacterial nanomaterials used to decorate medical devices and implants are
reviewed here as well.
PMID- 28419242
TI - Quantifying the impact of rising food prices on child mortality in India: a cross
district statistical analysis of the District Level Household Survey.
PMID- 28419241
TI - Central Hypothyroidism Due to a TRHR Mutation Causing Impaired Ligand Affinity
and Transactivation of Gq.
AB - Context: Central congenital hypothyroidism (CCH) is an underdiagnosed disorder
characterized by deficient production and bioactivity of thyroid-stimulating
hormone (TSH) leading to low thyroid hormone synthesis. Thyrotropin-releasing
hormone (TRH) receptor (TRHR) defects are rare recessive disorders usually
associated with incidentally identified CCH and short stature in childhood.
Objectives: Clinical and genetic characterization of a consanguineous family of
Roma origin with central hypothyroidism and identification of underlying
molecular mechanisms. Design: All family members were phenotyped with thyroid
hormone profiles, pituitary magnetic resonance imaging, TRH tests, and dynamic
tests for other pituitary hormones. Candidate TRH, TRHR, TSHB, and IGSF1 genes
were screened for mutations. A mutant TRHR was characterized in vitro and by
molecular modeling. Results: A homozygous missense mutation in TRHR (c.392T > C;
p.I131T) was identified in an 8-year-old boy with moderate hypothyroidism (TSH:
2.61 mIU/L, Normal: 0.27 to 4.2; free thyroxine: 9.52 pmol/L, Normal: 10.9 to
25.7) who was overweight (body mass index: 20.4 kg/m2, p91) but had normal
stature (122 cm; -0.58 standard deviation). His mother, two brothers, and
grandmother were heterozygous for the mutation with isolated hyperthyrotropinemia
(TSH: 4.3 to 8 mIU/L). The I131T mutation, in TRHR intracellular loop 2,
decreases TRH affinity and increases the half-maximal effective concentration for
signaling. Modeling of TRHR-Gq complexes predicts that the mutation disrupts the
interaction between receptor and a hydrophobic pocket formed by Gq. Conclusions:
A unique missense TRHR defect identified in a consanguineous family is associated
with central hypothyroidism in homozygotes and hyperthyrotropinemia in
heterozygotes, suggesting compensatory elevation of TSH with reduced biopotency.
The I131T mutation decreases TRH binding and TRHR-Gq coupling and signaling.
PMID- 28419243
TI - Efficacy and Safety of Pubertal Induction Using 17beta-Estradiol in Transgirls.
AB - Context: Puberty suppression using gonadotropin-releasing hormone agonists,
followed by induction of the desired sex characteristics using sex steroids, has
been recommended by the current guidelines as the treatment of choice for gender
dysphoric adolescents, although little evidence is available. Aim: To evaluate
the efficacy and safety of estrogen treatment for pubertal induction in
transgirls (female-identifying adolescents assigned male at birth). Methods:
Twenty-eight adolescents treated with oral estrogen for >=1 year were included.
The Tanner stage, anthropometry, laboratory parameters, bone age, and body
composition were evaluated. Results: Breast development started within 3 months
in 83% of adolescents, and after 3 years, 86% had Tanner breast stage 4 to 5. The
hip circumference increased and the waist/hip ratio decreased. The median serum
estradiol was 100 pmol/L (range, 24 to 380) at the standard adult dose of 2 mg of
17beta-estradiol. The adult height standard deviation score was +1.9 (for
females). The body mass index standard deviation score, lean body mass
percentage, fat percentage, and blood pressure did not change. No abnormalities
of creatinine or liver enzymes were detected, and the hematocrit and hemoglobin
A1c did not change. One individual developed hyperprolactinemia during high-dose
ethinylestradiol treatment to limit growth. Conclusions: Pubertal induction using
estradiol is effective; however, an adult dose of 2 mg does not always result in
appropriate serum estradiol levels. Monitoring renal function, liver enzymes,
hematocrit, and hemoglobin A1c during pubertal induction with estradiol is not
necessary. Further studies are needed to establish effective and safe methods to
limit growth.
PMID- 28419245
TI - Support of the aortic wall: a histological study in sheep comparing a macroporous
mesh with low-porosity vascular graft of the same polyethylene terephthalate
material.
AB - OBJECTIVES: Wrapping with various materials was an early treatment for aortic
aneurysms. Wrapping with low-porosity vascular grafts has been associated with
graft migration and vascular erosion. An alternative is to use a macroporous mesh
(MPM) made of the same polymer (polyethylene terephalate). We compared the
histological outcome 1 year after wrapping sheep aortas with low-porosity grafts
versus MPM fabrics. METHODS: The 2 different fabrics were wrapped around the
aorta of 3 sheep. After 1 year the aortas were excised. The 2 wrapped segments of
aorta were compared with each other and control aorta. Histological examinations
and measurements were made of the layers of the aortic wall in 36 prespecified
locations in each of the 3 sheep. RESULTS: Both fabrics were consistently
surrounded by foreign body reaction and well-vascularized fibrosis. This was more
pronounced with the low-porosity vascular graft material which was poorly
incorporated and caused buckling at the transition between wrapped and unwrapped
aorta. Conversely, the MPM was fully incorporated, resulting in a composite
mesh/biological aortic wall. There was reduction of medial thickness with both
materials but it was locally more extreme due to the corrugations in the vascular
graft material. The findings were consistent between sampled locations and were
similar in the 3 animals. CONCLUSIONS: The different porosity and rigidity of the
materials influences their incorporation into the aortic wall. The incorporation
of the pliable MPM precludes the complications of migration and erosion which are
seen after wrapping with low-porosity prosthetic vascular graft material.
PMID- 28419244
TI - Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors
Through the mTORC1 Signaling Pathway.
AB - Background: Resolvin D1 and D2 are bioactive lipid mediators that are generated
from docosahexaenoic acid. Although recent preclinical studies suggest that these
compounds have antidepressant effects, their mechanisms of action remain unclear.
Methods: We investigated mechanisms underlying the antidepressant effects of
resolvin D1 and resolvin D2 in lipopolysaccharide (0.8 mg/kg, i.p.)-induced
depression model mice using a tail suspension test. Results: I.c.v. infusion of
resolvin D1 (10 ng) and resolvin D2 (10 ng) produced antidepressant effects;
these effects were significantly blocked by a resolvin D1 receptor antagonist
WRW4 (10 ug, i.c.v.) and a resolvin D2 receptor antagonist O-1918 (10 ug,
i.c.v.), respectively. The mammalian target of rapamycin complex 1 inhibitor
rapamycin (10 mg/kg, i.p.) and a mitogen-activated protein kinase kinase
inhibitor U0126 (5 ug, i.c.v.) significantly blocked the antidepressant effects
of resolvin D1 and resolvin D2. An AMPA receptor antagonist NBQX (10 mg/kg, i.p.)
and a phosphoinositide 3-kinase inhibitor LY294002 (3 ug, i.c.v.) blocked the
antidepressant effects of resolvin D1 significantly, but not of resolvin D2.
Bilateral infusions of resolvin D1 (0.3 ng/side) or resolvin D2 (0.3 ng/side)
into the medial prefrontal cortex or dentate gyrus of the hippocampus produced
antidepressant effects. Conclusions: These findings demonstrate that resolvin D1
and resolvin D2 produce antidepressant effects via the mammalian target of
rapamycin complex 1 signaling pathway, and that the medial prefrontal cortex and
dentate gyrus are important brain regions for these antidepressant effects. These
compounds and their receptors may be promising targets for the development of
novel rapid-acting antidepressants, like ketamine and scopolamine.
PMID- 28419246
TI - Quality assurance for a multicenter Phase II study of stereotactic ablative
radiotherapy for hepatocellular carcinoma <=5 cm: a planning dummy run.
AB - Objective: The Korean Radiation Oncology Group (12-02) investigated the outcome
of stereotactic ablative radiotherapy for hepatocellular carcinoma <=5 cm using
60 Gy in three fractions. To evaluate dosimetric differences and compliance in a
multicenter trial, a planning dummy run procedure was performed. Methods: All six
participating institutions were provided the contours of two dummy run cases.
Plans were performed following the study protocol to cover the planning target
volume with a minimum of 90% of the prescription dose and to satisfy the
constraints for organs at risk. We assessed the institutional variations in plans
using dose-volume histograms. Results: Different planning techniques were
applied: static intensity-modulated radiotherapy in two institutions, CyberKnife
in two institutions and RapidArc in two institutions. The conformity index of all
12 plans was <=1.2. In terms of the planning target volume coverage, all
participants followed our study protocol. For the second dummy run case, located
in Segment 8 near the heart, the minimum dose of the planning target volume
(D99%: dose covering 99% of the planning target volume) was variable because
there was no mention of constraints of D99% of the planning target volume in the
study protocol. As an important organ at risk, the normal liver volumes receiving
<17 Gy in all 12 plans were >700 ml. Conclusions: Dosimetric parameters showed
acceptable compliance with the study protocol. However, we found the possibility
of underdose to the planning target volume if the hepatocellular carcinoma lesion
was located near organs at risk such as the heart. Based on this dummy run, we
will conduct individual case reviews to minimize the effects of study protocol
deviation.
PMID- 28419247
TI - Cardioinhibitory and vasodepressor responses to different stressors on head-up
tilt.
PMID- 28419248
TI - Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup
analysis from the CheckMate 025 study.
AB - Background: Nivolumab improved overall survival (OS) and objective response rate
(ORR) versus everolimus in previously treated patients with advanced renal cell
carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We
report efficacy and safety in the global and Japanese populations (minimum follow
up: 26 months). Methods: Patients were randomized 1:1 to receive nivolumab 3
mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily.
Primary endpoint: OS, key secondary endpoints: ORR, progression-free survival and
safety. Results: Of 410 (nivolumab) and 411 (everolimus) patients, 37 (9%) and 26
(6%), respectively, were Japanese. Median OS for the global population was 26.0
months (nivolumab) and 19.7 months (everolimus; hazard ratio 0.73 [95% confidence
interval [CI]: 0.61-0.88]; P = 0.0006), with medians not reached for Japanese
patients. ORR for the global population was 26% (nivolumab) versus 5%
(everolimus; odds ratio 6.13; 95% CI: 3.77-9.95); ORR for Japanese patients: 43%
versus 8% (odds ratio 9.14; 95% CI: 1.76-88.33). In Japanese patients, any-grade
treatment-related adverse events (AEs) occurred in 78% (Grade 3-4, 19%; most
common, anemia [5%]) treated with nivolumab and 100% (Grade 3-4, 58%; most
common, hypertriglyceridemia [12%]) treated with everolimus; the most common with
nivolumab was diarrhea (19%) and with everolimus was stomatitis (77%). Quality of
life was stable in the nivolumab arm. Conclusions: With >2 years of follow-up,
Japanese patients had a higher response rate with nivolumab versus everolimus
that was more pronounced yet consistent with the global population, with median
OS not reached, and a favorable safety profile.
PMID- 28419249
TI - Cohort Profile: African Collaborative Center for Microbiome and Genomics
Research's (ACCME's) Human Papillomavirus (HPV) and Cervical Cancer Study.
PMID- 28419250
TI - Enhanced glycolysis, regulated by HIF-1alpha via MCT-4, promotes inflammation in
arsenite-induced carcinogenesis.
AB - Arsenite is well established as a human carcinogen, but the molecular mechanisms
leading to arsenite-induced carcinogenesis are complex and elusive. Accelerated
glycolysis, a common process in tumor cells called the Warburg effect, is
associated with various biological phenomena. However, the role of glycolysis
induced by arsenite is unknown. We have found that, with chronic exposure to
arsenite, L-02 cells undergo a metabolic shift to glycolysis. In liver cells
exposed to arsenite, hypoxia inducible factor-1alpha (HIF-1alpha) and
monocarboxylate transporter-4 (MCT-4) are over-expressed. MCT-4, directly
mediated by HIF-1alpha, maintains a high level of glycolysis, and the enhanced
glycolysis promotes pro-inflammatory properties, which are involved in arsenite
carcinogenesis. In addition, serum lactate and cytokines are higher in arsenite
exposed human populations, and there is a positive correlation between them.
Moreover, there is a positive relationship between lactate and cytokines with
arsenic in hair. In sum, these findings indicate that MCT-4, mediated by HIF
1alpha, enhances the glycolysis induced by arsenite. Lactate, the end product of
glycolysis, is released into the extracellular environment. The acidic
microenvironment promotes production of pro-inflammatory cytokines, which
contribute to arsenite-induced liver carcinogenesis. These results provide a link
between the induction of glycolysis and inflammation in liver cells exposed to
arsenite, and thus establish a previously unknown mechanism for arsenite-induced
hepatotoxicity.
PMID- 28419252
TI - Sensitive Determination of Cannabinoids in Whole Blood by LC-MS-MS After Rapid
Removal of Phospholipids by Filtration.
AB - Direct analysis of Delta9-tetrahydrocannabinol (THC) and other cannabinoids in
crude acetonitrile extracts of whole blood by liquid chromatography-tandem mass
spectrometry using pneumatically assisted electrospray ionization (LC-ESI-MS-MS)
was subjected to pronounced ion suppression from co-eluting phospholipids (PLs).
The interferences were mainly caused by the lysophosphatidylcholine and
lysophosphatidylethanolamine classes of PLs. The PLs were easily removed from
crude extracts by filtration through a sorbent with Lewis acid properties, which
typically increased the THC and cannabinol (CBN) signal intensities by a factor
of 5. Based on this technique, a simple high-throughput LC-MS-MS method was
developed for the determination of cannabinoids in 100 MUL samples of whole
blood. The lower limits of quantification were 0.2 MUg/L for THC, CBN,
cannabidiol (CBD) and Delta9-tetrahydrocannabinolic acid A (THCA-A) and 0.5 MUg/L
for 11-hydroxy-Delta9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-Delta9
tetrahydrocannabinol (THC-COOH). The mean ion suppression levels after clean-up
were 10% (THC), 9% (CBN), 17% (CBD), 0% (THC-OH), 2% (THC-COOH) and 9% (THCA-A)
at blood concentration levels of 1-10 MUg/L. The mean true extraction recoveries
were 97% (THC), 101% (CBN), 101% (CBD), 98% (THC-OH), 95% (THC-COOH) and 90%
(THCA-A) at the same concentration levels. The relative intra-laboratory
reproducibility standard deviations were <9% at concentrations of 1 MUg/L or
higher. The trueness expressed as the relative bias of the test results was
within +/-4% at concentrations of 1 MUg/L or higher.
PMID- 28419251
TI - Evaluating genetic variants associated with breast cancer risk in high and
moderate-penetrance genes in Asians.
AB - Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1,
BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes
CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast
cancer. In this study, we investigated whether there are additional variants in
these 13 genes associated with breast cancer among women of Asian ancestry. We
analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and
6624 controls of Asian descent included in the Breast Cancer Association
Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included
in the Shanghai Breast Cancer Genetics Study (SBCGS). We found three missense
variants with minor allele frequency (MAF) <0.05: rs80358978 (Gly2508Ser),
rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the BRCA2 gene, showing
statistically significant associations with breast cancer risk, with P-values of
1.2 * 10-4, 1.0 * 10-3 and 5.0 * 10-3, respectively. In addition, we found four
low-frequency variants (rs8176085, rs799923, rs8176173 and rs8176258) in the
BRCA1 gene, one common variant in the CHEK2 gene (rs9620817), and one common
variant in the PALB2 gene (rs13330119) associated with breast cancer risk at P <
0.01. Our study identified several new risk variants in BRCA1, BRCA2, CHEK2, and
PALB2 genes in relation to breast cancer risk in Asian women. These results
provide further insights that, in addition to the high/moderate penetrance
mutations, other low-penetrance variants in these genes may also contribute to
breast cancer risk.
PMID- 28419254
TI - Evidence of Zika Virus RNA Fragments in Aedes albopictus (Diptera: Culicidae)
Field-Collected Eggs From Camacari, Bahia, Brazil.
AB - A major mosquito-borne viral disease outbreak caused by Zika virus (ZIKV)
occurred in Bahia, Brazil, in 2015, largely due to transmission by the mosquito,
Aedes aegypti (L.). Detecting ZIKV in field samples of Ae. aegypti has proven
problematic in some locations, suggesting other mosquito species might be
contributing to the spread of ZIKV. In this study, several (five) adult Aedes
albopictus (Skuse) mosquitoes that emerged from a 2015 field collection of eggs
from Camacari, Bahia, Brazil, were positive for ZIKV RNA; however, attempts to
isolate live virus were not successful. Results from this study suggest that
field-collected Ae. albopictus eggs may contain ZIKV RNA that require further
tests for infectious ZIKV. There is a need to investigate the role of Ae.
albopictus in the ZIKV infection process in Brazil and to study the potential
presence of vertical and sexual transmission of ZIKV in this species.
PMID- 28419255
TI - Unannounced versus announced hospital surveys: a nationwide cluster-randomized
controlled trial.
AB - Objective: To evaluate the effectiveness of unannounced versus announced surveys
in detecting non-compliance with accreditation standards in public hospitals.
Design: A nationwide cluster-randomized controlled trial. Setting and
participants: All public hospitals in Denmark were invited. Twenty-three
hospitals (77%) (3 university hospitals, 5 psychiatric hospitals and 15 general
hospitals) agreed to participate. Intervention: Twelve hospitals were randomized
to receive unannounced surveys (intervention group) and eleven hospitals to
receive announced surveys (control group). We hypothesized that the hospitals
receiving the unannounced surveys would reveal a higher degree of non-compliance
with accreditation standards than the hospitals receiving announced surveys. Nine
surveyors trained and employed by the Danish Institute for Quality and
Accreditation in Healthcare (IKAS) were randomized into teams and conducted all
surveys. Main outcome measure: The outcome was the surveyors' assessment of the
hospitals' level of compliance with 113 performance indicators-an abbreviated set
of the Danish Healthcare Quality Programme (DDKM) version 2, covering
organizational standards, patient pathway standards and patient safety standards.
Compliance with performance indicators was analyzed using binomial regression
analysis with bootstrapped robust standard errors. Results: In all, 16 202
measurements were acceptable for data analysis. The risk of observing non
compliance with performance indicators for the intervention group compared with
the control group was statistically insignificant (risk difference (RD) = -0.6
percentage points [-2.51-1.31], P = 0.54). A converged analysis of the six
patient safety critical standards, requiring 100% compliance to gain
accreditation status revealed no statistically significant difference (RD = -0.78
percentage points [-4.01-2.44], P = 0.99). Conclusions: Unannounced hospital
surveys were not more effective than announced surveys in detecting quality
problems in Danish hospitals. Trial Registration number: ClinicalTrials.gov
NCT02348567, https://clinicaltrials.gov/ct2/show/NCT02348567?term=NCT02348567.
PMID- 28419256
TI - ChloroMitoCU: Codon patterns across organelle genomes for functional genomics and
evolutionary applications.
AB - Organelle genomes are widely thought to have arisen from reduction events
involving cyanobacterial and archaeal genomes, in the case of chloroplasts, or
alpha-proteobacterial genomes, in the case of mitochondria. Heterogeneity in base
composition and codon preference has long been the subject of investigation of
topics ranging from phylogenetic distortion to the design of overexpression
cassettes for transgenic expression. From the overexpression point of view, it is
critical to systematically analyze the codon usage patterns of the organelle
genomes. In light of the importance of codon usage patterns in the development of
hyper-expression organelle transgenics, we present ChloroMitoCU, the first-ever
curated, web-based reference catalog of the codon usage patterns in organelle
genomes. ChloroMitoCU contains the pre-compiled codon usage patterns of 328
chloroplast genomes (29,960 CDS) and 3,502 mitochondrial genomes (49,066 CDS),
enabling genome-wide exploration and comparative analysis of codon usage patterns
across species. ChloroMitoCU allows the phylogenetic comparison of codon usage
patterns across organelle genomes, the prediction of codon usage patterns based
on user-submitted transcripts or assembled organelle genes, and comparative
analysis with the pre-compiled patterns across species of interest. ChloroMitoCU
can increase our understanding of the biased patterns of codon usage in organelle
genomes across multiple clades. ChloroMitoCU can be accessed at:
http://chloromitocu.cgu.edu.tw/.
PMID- 28419257
TI - Rodent-Pika Parasite Spillover in Western North America.
AB - Competition during the Cenozoic expansion of the Rodentia may have contributed to
ecological niche reduction of pikas, which are now increasingly under threat as
their habitat degrades under global climate change, while some rodents expand
their ranges and overlap with pikas. Range overlap carries the possibility of
disease spillover. Contemporary North American pikas are cold-adapted and
relegated primarily to alpine environments where they subsist on relatively low
quality herbaceous diet. Yet their evolutionary ancestors were distributed
geographically even into the subtropics. Here we examine historical and
contemporary records of fleas on pikas (Ochotona princeps) from sites at
different elevations in the Sierra Nevada and Rocky Mountains and the Pacific
Northwest. We calculated indices of diversity from each site and spillover
fraction, i.e., the proportion of fleas on pikas that have a preference for
rodents. Across this range there are four pika specialist flea species, with no
more than two of these per site, and 18 characteristically rodent flea species.
Diversity is greatest in the Pacific Northwest and lowest in Montana. Rodent flea
spillover onto pikas declines with elevation in the Rocky Mountains. These data
provide evidence that rodents and pikas interact enough to allow considerable
parasite spillover, and which could be exacerbated as pikas are increasingly
stressed by climate change at lower elevations some rodent species expand up
elevation in the face of increasing global warming. With global climate change,
both biotic and abiotic niche shrinkage demand our attention.
PMID- 28419258
TI - EigenTHREADER: analogous protein fold recognition by efficient contact map
threading.
AB - Motivation: Protein fold recognition when appropriate, evolutionarily-related,
structural templates can be identified is often trivial and may even be viewed as
a solved problem. However in cases where no homologous structural templates can
be detected, fold recognition is a notoriously difficult problem ( Moult et al.,
2014 ). Here we present EigenTHREADER, a novel fold recognition method capable of
identifying folds where no homologous structures can be identified. EigenTHREADER
takes a query amino acid sequence, generates a map of intra-residue contacts, and
then searches a library of contact maps of known structures. To allow the contact
maps to be compared, we use eigenvector decomposition to resolve the principal
eigenvectors these can then be aligned using standard dynamic programming
algorithms. The approach is similar to the Al-Eigen approach of Di Lena et al.
(2010) , but with improvements made both to speed and accuracy. With this search
strategy, EigenTHREADER does not depend directly on sequence homology between the
target protein and entries in the fold library to generate models. This in turn
enables EigenTHREADER to correctly identify analogous folds where little or no
sequence homology information is. Results: EigenTHREADER outperforms well
established fold recognition methods such as pGenTHREADER and HHSearch in terms
of True Positive Rate in the difficult task of analogous fold recognition. This
should allow template-based modelling to be extended to many new protein families
that were previously intractable to homology based fold recognition methods.
Availability and implementation: All code used to generate these results and the
computational protocol can be downloaded from
https://github.com/DanBuchan/eigen_scripts . EigenTHREADER, the benchmark code
and the data this paper is based on can be downloaded from:
http://bioinfadmin.cs.ucl.ac.uk/downloads/eigenTHREADER/ . Contact:
d.t.jones@ucl.ac.uk.
PMID- 28419260
TI - Mitochondria-targeted small molecule SS31: a potential candidate for the
treatment of Alzheimer's disease.
PMID- 28419259
TI - Adjunctive Corticosteroid Therapy in the Treatment of Coccidioidal Meningitis.
AB - Coccidioidal meningitis (CM) has high morbidity, and adjunctive measures to
improve outcomes are needed. Using an established multicenter retrospective
cohort study of CM (N = 221), we found that patients receiving adjunctive
corticosteroids had a significant reduction in secondary cerebrovascular events
(P = .0049). Those with CM-associated cerebrovascular events (8%) may benefit
from short-term corticosteroids.
PMID- 28419262
TI - Death, disease and indignity: serious health and human rights concerns persist in
UK Immigration Detention Facilities.
PMID- 28419261
TI - Challenges in adapting existing clinical natural language processing systems to
multiple, diverse health care settings.
AB - Objective: Widespread application of clinical natural language processing (NLP)
systems requires taking existing NLP systems and adapting them to diverse and
heterogeneous settings. We describe the challenges faced and lessons learned in
adapting an existing NLP system for measuring colonoscopy quality. Materials and
Methods: Colonoscopy and pathology reports from 4 settings during 2013-2015,
varying by geographic location, practice type, compensation structure, and
electronic health record. Results: Though successful, adaptation required
considerably more time and effort than anticipated. Typical NLP challenges in
assembling corpora, diverse report structures, and idiosyncratic linguistic
content were greatly magnified. Discussion: Strategies for addressing adaptation
challenges include assessing site-specific diversity, setting realistic
timelines, leveraging local electronic health record expertise, and undertaking
extensive iterative development. More research is needed on how to make it easier
to adapt NLP systems to new clinical settings. Conclusions: A key challenge in
widespread application of NLP is adapting existing systems to new clinical
settings.
PMID- 28419263
TI - Renal Toxicity in Pediatric Patients Receiving Cidofovir for the Treatment of
Adenovirus Infection.
AB - Treatment options for adenovirus infection in immunocompromised children are
limited. Nephrotoxicity has been associated with cidofovir use, but the rate of
cidofovir-associated nephrotoxicity in pediatric patients is unclear. In a
retrospective review of patients with adenovirus infection treated with
cidofovir, neonates (n = 5) had higher viral loads and shorter times to renal
insufficiency than older children (n = 24). Higher weekly doses of cidofovir were
associated with greater increases in creatinine levels. Of 29 courses of
cidofovir, 9 were complicated by acute kidney injury; in these children,
mortality was high. Cidofovir dosing in children needs to be optimized, and other
therapeutic alternatives should be developed.
PMID- 28419264
TI - Evaluating the impact of contracting out basic health care services in the state
of Sao Paulo, Brazil.
AB - As a means of dealing with shortcomings in the coverage, quality and efficiency
of the public health care sector, several municipalities in the state of Sao
Paulo, Brazil, have started to contract pre-certified non-profit or non
governmental organizations to take part in the delivery of health care
services.This paper explores the impact of introducing these contracts in the
primary health care sector. Using data on the 645 municipalities in the state of
Sao Paulo and difference-in-differences methods, we estimate the effect of
contracting out in the primary health care sector on various dimensions of
mortality and health care use. The results show that implementation of the
contracting out strategy significantly increases the number of primary health
care appointments by approximately one appointment per user of the national
health care system per year. Point estimates indicate a reducing effect on
hospitalization for preventable diseases.
PMID- 28419266
TI - The Effect of Parasitism and Interpopulation Hybridization on Aedes albopictus
(Diptera: Culicidae) Fitness.
AB - Recent research in mosquito population genetics suggests that interpopulation
hybridization has likely contributed to the rapid spread of the container
breeding mosquitoes. Here, I used laboratory experiments to investigate whether
interpopulation Aedes (Stegomyia) albopictus (Skuse) F1 and F2 hybrids exhibit
higher fitness than parental populations, and whether hybrid mosquito performance
is related to infection by the coevolved protozoan parasite Ascogregarina
taiwanensis (Lien and Levine). Overall, there were significant differences in
development time, wing length, and survival between the two parental mosquito
populations, but no difference in per capita growth rate r. Hybrid mosquitoes
were generally intermediate in phenotype to the parentals, except that F2 females
were significantly larger than the midparent average. In addition, As.
taiwanensis parasites produced fewest oocysts when they were reared in hosts of
hybrid origin. These data suggest that hybridization between previously isolated
mosquito populations can result in slight increases in potential mosquito
reproductive success, via increased hybrid body size, and via the temporary
escape from coevolved parasites. These findings are significant because studies
have shown that even slight hybrid vigor can have positive fitness consequences
for population persistence. Although this was a laboratory experiment extending
only to the F2 generation, many other invasive insects also carry coevolved
parasites, and thus the patterns seen in this mosquito system may be broadly
relevant.
PMID- 28419265
TI - Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis.
AB - What's Known on This Subject: Neonates are at increased risk for developing
sepsis, but this population often exhibits ambiguous clinical signs that
complicate the diagnosis of infection. No biomarker has yet shown enough
diagnostic accuracy to rule out sepsis at the time of clinical suspicion. What
This Study Adds: We show that a gene-expression-based signature is an accurate
objective measure of the risk of sepsis in a neonate or preterm infant, and it
substantially improves diagnostic accuracy over that of commonly used laboratory
based testing. Implementation might decrease inappropriate antibiotic use.
Background: Neonatal sepsis can have devastating consequences, but accurate
diagnosis is difficult. As a result, up to 200 neonates with suspected sepsis are
treated with empiric antibiotics for every 1 case of microbiologically confirmed
sepsis. These unnecessary antibiotics enhance bacterial antibiotic resistance,
increase economic costs, and alter gut microbiota composition. We recently
reported an 11-gene diagnostic test for sepsis (Sepsis MetaScore) based on host
whole-blood gene expression in children and adults, but this test has not been
evaluated in neonates. Methods: We identified existing gene expression microarray
based cohorts of neonates with sepsis. We then tested the accuracy of the Sepsis
MetaScore both alone and in combination with standard diagnostic laboratory tests
in diagnosing sepsis. Results: We found 3 cohorts with a total of 213 samples
from control neonates and neonates with sepsis. The Sepsis MetaScore had an area
under the receiver operating characteristic curve of 0.92-0.93 in all 3 cohorts.
We also found that, as a diagnostic test for sepsis, it outperformed standard
laboratory measurements alone and, when used in combination with another test(s),
resulted in a significant net reclassification index (0.3-0.69) in 5 of 6
comparisons. The mean point estimates for sensitivity and specificity were 95%
and 60%, respectively, which, if confirmed prospectively and applied in a high
risk cohort, could reduce inappropriate antibiotic usage substantially.
Conclusions: The Sepsis MetaScore had excellent diagnostic accuracy across 3
separate cohorts of neonates from 3 different countries. Further prospective
targeted study will be needed before clinical application.
PMID- 28419267
TI - A national survey assessing the number of records allowed open in electronic
health records at hospitals and ambulatory sites.
AB - To reduce the risk of wrong-patient errors, safety experts recommend limiting the
number of patient records providers can open at once in electronic health records
(EHRs). However, it is unknown whether health care organizations follow this
recommendation or what rationales drive their decisions. To address this gap, we
conducted an electronic survey via 2 national listservs. Among 167 inpatient and
outpatient study facilities using EHR systems designed to open multiple records
at once, 44.3% were configured to allow >=3 records open at once (unrestricted),
38.3% allowed only 1 record open (restricted), and 17.4% allowed 2 records open
(hedged). Decision-making centered on efforts to balance safety and efficiency,
but there was disagreement among organizations about how to achieve that balance.
Results demonstrate no consensus on the number of records to be allowed open at
once in EHRs. Rigorous studies are needed to determine the optimal number of
records that balances safety and efficiency.
PMID- 28419268
TI - The American Society for Clinical Pathology's 2015 Wage Survey of Medical
Laboratories in the United States.
AB - Objectives: To inform the pathology and laboratory field of the most recent
national wage data from the American Society for Clinical Pathology (ASCP).
Historically, the results of this biennial survey have served as a basis for
additional research on laboratory recruitment, retention, education, marketing,
certification, and advocacy. Methods: The 2015 wage survey was conducted through
collaboration between the ASCP's Institute of Science, Technology, and Policy in
Washington, DC, and the ASCP Board of Certification in Chicago, Illinois.
Electronic survey invitations were sent to individuals who are currently
practicing in the field. Results: Data reveal increased salaries since 2013 for
all staff-level laboratory professionals surveyed except phlebotomists and
pathologists' assistants. Laboratory assistants and phlebotomists, regardless of
level, continue to have lower salaries while pathologists' assistants and
administration personnel have higher salaries than the rest of the laboratory
professions surveyed. Conclusions: Survey results put emphasis on strategic
recruitment and retention by laboratory training programs and institutions that
hire laboratory professionals.
PMID- 28419269
TI - Dual-Genotype Diffuse Low-Grade Glioma: Is It Really Time to Abandon
Oligoastrocytoma As a Distinct Entity?
AB - We report a unique case of dual-genotype oligoastrocytoma characterized by IDH2
gene mutation. The tumor was resected from the temporal lobe of a 25-year-old
man. At histological examination with hematoxylin and eosin stain, it showed
distinct oligodendroglial and astrocytic areas. The former retained alpha
thalassaemia/mental retardation X-linked (ATRX) immuno-expression and had absent
staining for p53, while the latter had ATRX loss and p53 over-expression.
Molecular analyses were separately assessed in the 2 tumor components. Gene
sequencing disclosed IDH2 mutation in both, whereas oligodendroglial, but not
astrocytic areas, had 1p/19q codeletion and telomerase reverse transcriptase
promoter mutation. Distinction of dual-genotype oligoastrocytoma from
oligodendroglioma and astrocytoma might be clinically relevant for prognosis and
therapy. Because most studies that investigated the molecular phenotype of
oligoastrocytomas have focused on IDH1 R132H mutated cases, we suggest further
analyses on diffuse gliomas with heterogeneous (astrocytic and oligodendroglial)
morphology before oligoastrocytoma is dismissed as a distinct nosological entity.
PMID- 28419270
TI - Raltegravir plus lamivudine as 'maintenance therapy' in suppressed HIV-1-infected
patients in real-life settings.
PMID- 28419271
TI - Genetic testing for familial hypercholesterolaemia is essential in individuals
with high LDL cholesterol: who does it in the world?
PMID- 28419272
TI - Insecticidal and Behavioral Avoidance Responses of Anopheles minimus and Culex
quinquefasciatus (Diptera: Culicidae) to Three Synthetic Repellents.
AB - Escape responses, knockdown (KD), and toxicity of laboratory strains of Anopheles
minimus Theobald and Culex quinquefasciatus Say to three synthetic mosquito
repellents, DEET (N, N-diethyl-3-methylbenzamide), IR3535, or picaridin, at 5%
v/v concentrations, were evaluated using repellent-treated papers in standard WHO
tube assays and an excito-repellency (ER) test chamber system. The tube assays
recorded knockdown effects of each repellent immediately after 30-min exposure
and the final morality following a 24-h holding period. DEET showed 100% KD at 30
min and complete toxicity at 24 h against both species. Both actions were either
minimal or absent for IR3535 and picaridin, respectively. Culex quinquefasciatus
showed significantly greater escape with DEET compared with the other compounds
in both contact irritancy (excitation) and noncontact spatial repellency trials.
Anopheles minimus showed much more pronounced irritancy and repellency flight
escape to IR3535 than picaridin. DEET was the most active irritant and repellent
compound against Cx. quinquefasciatus. When adjusting contact test responses
based on paired noncontact repellency assays, DEET and IR3535 showed much
stronger spatial repellent properties than irritancy with An. minimus. Picaridin
performed poorly as an irritant or repellent against both species. We conclude
that DEET, followed by IR3535, act as strong spatial repellents at 5%
concentration. DEET also performs as a strong toxicant. Our findings show that
different mosquitoes can respond contrastingly to repellents, thus the importance
to test a wider range of species and populations to assess the full range of
chemical action.
PMID- 28419273
TI - Habitat and Density of Oviposition Opportunity Influences Aedes aegypti (Diptera:
Culicidae) Flight Distance.
AB - Understanding the dispersal of Aedes (aegypti (L.) Diptera: Culicidae) after
consuming a potentially infectious bloodmeal is an important part of controlling
the spread of the arboviruses it transmits. Because of the impact on abundance,
removal of oviposition sites is a key component of vector control. However,
source reduction around a case may encourage dispersal of potentially infected
vectors. We compare the effect of oviposition site availability on Ae. aegypti
dispersal behavior within 30-m linear cages in three model ecosystems at the
University of Arizona's Biosphere 2 research facility. We found a significant
interaction effect in which, when oviposition site density was sparse, dispersal
was greater in the highly vegetated humid rainforest and limited in the low
vegetation, arid desert model ecosystem. When oviposition site density was dense,
no significant effect on dispersal was observed. These analyses support the idea
that source reduction has an important influence on the distance that gravid,
potentially infected, females will travel.
PMID- 28419274
TI - Extreme high high-density lipoprotein cholesterol is paradoxically associated
with high mortality in men and women: two prospective cohort studies.
AB - Aims: High-density lipoprotein (HDL) cholesterol concentrations are inversely
associated with cardiovascular disease and mortality across a range of
concentrations, but genetic evidence suggest that extreme high concentrations may
paradoxically lead to more cardiovascular disease. We tested the hypothesis that
extreme high concentrations of HDL cholesterol are associated with high all-cause
mortality in men and women. Methods and results: A total of 52 268 men and 64 240
women were included from the two prospective population-based studies, the
Copenhagen City Heart Study and the Copenhagen General Population Study. During
745 452 person-years of follow-up, number of deaths from any cause were 5619
(mortality rate, 17.1/1000 person-years (95% confidence interval (CI): 16.7
17.6)) in men and 5059 (mortality rate, 12.1/1000 person-years (11.8-12.4)) in
women. The association between HDL cholesterol concentrations and all-cause
mortality was U-shaped for both men and women, with both extreme high and low
concentrations being associated with high all-cause mortality risk. The
concentration of HDL cholesterol associated with the lowest all-cause mortality
was 1.9 mmol/L (95% CI: 1.4-2.0) (73 mg/dL (54-77)) in men and 2.4 mmol/L (1.8
2.5) (93 mg/dL (69-97)) in women. When compared with the groups with the lowest
risk, the multifactorially adjusted hazard ratios for all-cause mortality were
1.36 (95% CI: 1.09-1.70) for men with HDL cholesterol of 2.5-2.99 mmol/L (97-115
mg/dL) and 2.06 (1.44-2.95) for men with HDL cholesterol >=3.0 mmol/L (116
mg/dL). For women, corresponding hazard ratios were 1.10 (0.83-1.46) for HDL
cholesterol of 3.0-3.49 mmol/L (116-134 mg/dL) and 1.68 (1.09-2.58) for HDL
cholesterol >=3.5 mmol/L (135 mg/dL). Conclusion: Men and women in the general
population with extreme high HDL cholesterol paradoxically have high all-cause
mortality. These findings need confirmation in other studies.
PMID- 28419275
TI - Clinical Care Guideline for Improving Pediatric Acute Musculoskeletal Infection
Outcomes.
AB - Background: Acute pediatric musculoskeletal infections are common, leading to
significant use of resources and antimicrobial exposure. In order to decrease
variability and improve the quality of care, Children's Hospital Colorado
implemented a clinical care guideline (CCG) for these infections. The purpose of
this study is to evaluate clinical and resource outcomes PRE and POST this CCG.
Methods: Retrospective chart review evaluated patients admitted to a large
pediatric quaternary referral center (CHCO) diagnosed with acute osteomyelitis,
septic arthritis, pyomyositis, and/or musculoskeletal abscess prior to and after
guideline implementation. Primary outcomes included length of stay and overall
antibiotic use, with additional secondary clinical, process, and therapeutic
outcomes examined. Results: 82 patients were identified in both the pre-CCG and
post-CCG cohorts. There was a reduction in the median of all primary outcomes,
including length of stay (0.6 median days decrease, P = .04), length of IV
antibiotic therapy (4.9 median days decrease, P < .0001), and days of IV
antibiotic therapy (6.4 median days decrease, P = .0004). Our median length of
stay post-CCG was 4.9 days, the shortest reported length of stay for pediatric
acute musculoskeletal infections to date. Additionally, there was a 24.5 hour
reduction in median length of fever (P = .02), faster CRP normalization (P <
.0001), 50% decrease in the number of related readmissions (P = .02), 34%
decrease in central venous catheters placed (P < .0001), decreased time to first
culture (P = .02), and 79% pathogen identification post-CCG (P = .056).
Conclusions: Implementation of a CCG for acute musculoskeletal infections
improves patient, process and resource outcomes.
PMID- 28419276
TI - Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human
Immunodeficiency Virus Type 1.
AB - Background.: Investigations into which human immunodeficiency virus type 1 (HIV
1) sequence features may be selected for transmission during sexual exposure have
been hampered by the small number of characterized transmission pairs in
individual studies. Methods.: To boost statistical power to detect differences in
glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we
reanalyzed all available 2485 env sequences derived from 114 subjects
representing 58 transmission pairs from previous studies using mixed-effects
linear regression and an approach to approximate the unobserved transmitted
virus. Results.: The recipient partner had a shorter V1-V4 region and fewer
potential N-linked glycosylation sites (PNGS) than sequences from the source
partner. We also detected a trend toward more PNGS and lower isoelectric points
in transmitted sequences with source partner and the evolutionary tendency to
shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points
in the recipient following transmission. Conclusions.: By using all available
well-characterized env sequences from transmission pairs via sexual exposure, we
were able to identify several important virologic factors that may be important
in the development of biomedical preventive interventions.
PMID- 28419277
TI - Prevention of TB using rifampicin plus isoniazid reduces nevirapine
concentrations in HIV-exposed infants.
AB - Background: Newborns of HIV-infected mothers are given daily doses of nevirapine
to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive
TB preventive therapy. TB preventive regimens include isoniazid for 6 months or
rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of
concomitant RH preventive therapy on nevirapine concentrations in infants is
unknown. Patients and methods: Tshepiso was a prospective case-control cohort
study of pregnant HIV-infected women with and without TB whose newborn infants
received standard doses of nevirapine for HIV prophylaxis. Infants born to
mothers with TB also received RH preventive therapy. Infant plasma nevirapine
concentrations were measured at 1 and 6 weeks. The effects of RH preventive
therapy on nevirapine disposition were investigated in a population
pharmacokinetic model. Results: Of 164 infants undergoing pharmacokinetic
sampling, 46 received RH preventive therapy. After adjusting for weight using
allometric scaling, the model estimated a 33% reduction in nevirapine trough
concentrations with RH preventive therapy compared with TB-unexposed infants not
receiving concomitant rifampicin and a 30% decline in trough concentrations in a
typical infant between day 7 and 35 post-partum. Conclusions: Rifampicin-based TB
preventative treatment reduces nevirapine concentrations significantly in HIV
exposed infants. Although the nevirapine exposures required to prevent HIV
acquisition in breastfeeding infants are undefined, given the potential risks
associated with underdosing nevirapine in this setting, it is prudent to avoid
rifampicin-based preventive therapy in HIV-exposed children receiving
prophylactic nevirapine.
PMID- 28419278
TI - Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co
regulation as a predictor of prostate cancer recurrence.
PMID- 28419279
TI - Primates, Lice and Bacteria: Speciation and Genome Evolution in the Symbionts of
Hominid Lice.
AB - Insects with restricted diets rely on symbiotic bacteria to provide essential
metabolites missing in their diet. The blood-sucking lice are obligate, host
specific parasites of mammals and are themselves host to symbiotic bacteria. In
human lice, these bacterial symbionts supply the lice with B-vitamins. Here, we
sequenced the genomes of symbiotic and heritable bacterial of human, chimpanzee,
gorilla, and monkey lice and used phylogenomics to investigate their evolutionary
relationships. We find that these symbionts have a phylogenetic history
reflecting the louse phylogeny, a finding contrary to previous reports of
symbiont replacement. Examination of the highly reduced symbiont genomes (0.53
0.57 Mb) reveals much of the genomes are dedicated to vitamin synthesis. This is
unchanged in the smallest symbiont genome and one that appears to have been
reorganized. Specifically, symbionts from human lice, chimpanzee lice, and
gorilla lice carry a small plasmid that encodes synthesis of vitamin B5, a
vitamin critical to the bacteria-louse symbiosis. This plasmid is absent in an
old world monkey louse symbiont, where this pathway is on its primary chromosome.
This suggests the unique genomic configuration brought about by the plasmid is
not essential for symbiosis, but once obtained, it has persisted for up to 25 My.
We also find evidence that human, chimpanzee, and gorilla louse endosymbionts
have lost a pathway for synthesis of vitamin B1, whereas the monkey louse
symbiont has retained this pathway. It is unclear whether these changes are
adaptive, but they may point to evolutionary responses of louse symbionts to
shifts in primate biology.
PMID- 28419280
TI - Fractional flow reserve and pressure-bounded coronary flow reserve to predict
outcomes in coronary artery disease.
AB - Aims: Fractional flow reserve (FFR) has proven to its prognostic and therapeutic
value. However, the additive prognostic value of coronary flow reserve (CFR)
remains unclear. This study sought to investigate the clinical utility of
combined FFR and CFR measurements to predict outcomes. Methods and results: Using
the prospective, multicentre Interventional Cardiology Research Incooperation
Society-FFR registry, a total of 2088 lesions from 1837 patients were included in
this substudy. Based on baseline and hyperaemic pressure gradients, we computed
physiologic limits of CFR [the so called pressure-bounded (pb) CFR] and
classified lesions as low (<2) or high (>=2). The primary endpoint was major
adverse cardiac events (MACE, a composite of cardiac death, myocardial
infarction, and revascularization) analysed on a per-patient basis. During a
median follow-up of 1.9 years (inter-quartile range: 1.0-3.0 years), MACE
occurred in 5.7% of patients with FFR <=0.80 vs. 2.8% of patients with FFR >0.80
[adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19-3.89; P =
0.011. In contrast, the incidence of MACE did not differ between patients with pb
CFR < 2 vs. pb-CFR >= 2 (4.2% vs. 4.2%; aHR: 0.98, CI: 0.60 to 1.58; P = 0.92).
Incorporation of FFR significantly improved model prediction of MACE (global chi2
38.8-48.1, P = 0.002). However, pb-CFR demonstrated no incremental utility to
classify outcomes (global chi2 48.1-48.2, P > 0.99). Conclusions: In this large,
prospective registry of over 2000 coronary lesions, FFR was strongly associated
with clinical outcomes. In contrast, a significant association between pb-CFR and
clinical events could not be determined and adding knowledge of pb-CFR did not
improve prognostication over FFR alone.
PMID- 28419281
TI - Expression of the Plasmodium falciparum Clonally Variant clag3 Genes in Human
Infections.
AB - Background: Many genes of the malaria parasite Plasmodium falciparum show
clonally variant expression regulated at the epigenetic level. These genes
participate in fundamental host-parasite interactions and contribute to adaptive
processes. However, little is known about their expression patterns during human
infections. A peculiar case of clonally variant genes are the 2 nearly identical
clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to
resistance to some toxic compounds. Methods: We developed a procedure to
characterize the expression of clag3 genes in naturally infected patients and in
experimentally infected human volunteers. Results: We provide the first
description of clag3 expression during human infections, which revealed mutually
exclusive expression and identified the gene predominantly expressed. Adaptation
to culture conditions or selection with a toxic compound resulted in isolate
dependent changes in clag3 expression. We also found that clag3 expression
patterns were reset during transmission stages. Conclusions: Different
environment conditions select for parasites with different clag3 expression
patterns, implying functional differences between the proteins encoded. The
epigenetic memory is likely erased before parasites start infection of a new
human host. Altogether, our findings support the idea that clonally variant genes
facilitate the adaptation of parasite populations to changing conditions through
bet-hedging strategies.
PMID- 28419282
TI - Autologous Haematopoietic Stem Cell Transplantation for Refractory Crohn's
Disease: Efficacy in a Single-Centre Cohort.
AB - Background: Haematopoietic stem cell transplantation [HSCT] is considered a
therapeutic option for patients with severe Crohn's disease [CD] unresponsive to
currently available therapies. Methods: Autologous HSCT was considered for CD
patients with active disease, unresponsive or intolerant to approved medications
and unsuitable for surgery. After HSCT, patients were closely followed up every 6
weeks during the first 2 years and every 6 months thereafter up to 5 years.
Colonoscopy and/or magnetic resonance imaging were performed at Months 6, 12, 24,
and 48 after HSCT. Results: From December 1, 2007 to December 31, 2015, 37 CD
patients were assessed for HSCT. Of these, 35 patients [13 within the ASTIC
trial] underwent mobilisation. Six patients did not complete the transplant for
various reasons and 29 patients were finally transplanted. Patients were followed
up during a median of 12 months [6-60]. At 6 months, 70% of patients achieved
drug-free clinical remission (Crohn's Disease Index of Severity [CDAI] < 150).
The proportion of patients in drug-free remission (CDAI < 150, Simple Endoscopic
activity Score [SES]-CD < 7] was 61% at 1 year, 52% at 2 years, 47% at 3 years,
39% at 4 years, and 15% at 5 years. Patients who relapsed were re-treated and 80%
regained clinical remission. Six out of the 29 [21%] required surgery. One
patient died due to systemic cytomegalovirus infection 2 months after transplant.
Conclusions: HSCT is a salvage therapy for patients with extensive and refractory
CD. Although relapse occurs in a majority of patients within 5 years after
transplant, drug responsiveness is regained and clinical remission achieved in
80% of cases.
PMID- 28419283
TI - DNA-Based Identification of Forensically Important Blow Flies (Diptera:
Calliphoridae) From India.
AB - Correct species identification is the first and the most important criteria in
entomological evidence-based postmortem interval (PMI) estimation. Although
morphological keys are available for species identification of adult blow flies,
keys for immature stages are either lacking or are incomplete. In this study,
cytochrome oxidase subunit 1 (COI) reference data were developed from nine
species (belonging to three subfamilies, namely, Calliphorinae, Luciliinae, and
Chrysomyinae) of blow flies from India. Seven of the nine species included in
this study were found suitable for DNA-based identification using COI gene,
because they showed nonoverlapping intra- (0.0-0.3%) and inter-(1.96-18.14%)
specific diversity, and formed well-supported monophyletic clade in phylogenetic
analysis. The remaining two species (i.e., Chrysomya megacephala (Fabricius) and
Chrysomya chani Kurahashi) cannot be distinguished reliably using our database
because they had a very low interspecific diversity (0.11%), and Ch. megacephala
was paraphyletic with respect to Ch. chani in the phylogenetic analysis. We
conclude that the COI gene is a useful marker for DNA-based identification of
blow flies from India.
PMID- 28419284
TI - Laser Thermal Ablation for Metastases Failing Radiosurgery: A Multicentered
Retrospective Study.
AB - BACKGROUND: Radiosurgical failure following stereotactic radiosurgery for brain
metastases can be attributed to tumor regrowth or radiation necrosis. MRI-guided
laser thermal ablation (LTA) therapy has emerged as an option for treatment;
however, previous literature demonstrates variable results across centers.
OBJECTIVE: To assess the outcomes of LTA in the treatment of metastases failing
radiosurgery across multiple centers and to determine if any treatment factors
are predictive of outcome. METHODS: Clinical data for 30 patients across 4
centers were retrospectively reviewed. Patients were included if they received
LTA therapy following radiosurgical failure due to radiation necrosis or tumor
regrowth. Demographics, surgical data, and follow-up imaging and clinical
information were collected. Linear regression analyses were performed to
determine treatment factors that were associated with post-LTA outcome. RESULTS:
The large majority of patients responded favorably to LTA treatment with low
complication rates (23%), short length of stay (53% <= 2 d) and reductions in
perilesional edema (63%). A total of 73.3% of patients stopped steroids and 48%
saw improvement of their preoperative symptoms. Patients with better pre-LTA
Karnofsky Performance Status had better survival. Patients who had lesions with
more perilesional T2 change post-LTA had a better chance of weaning off steroids
and obtaining symptomatic relief. CONCLUSION: MRI-guided laser thermal ablation
therapy serves as a viable alternative to traditional treatment options for
metastatic brain lesions failing radiosurgery. Although this study is limited by
size and is retrospective, LTA therapy may result in symptomatic improvement and
a more prominent reduction in fluid-attenuated inversion-recovery signal for
larger lesions.
PMID- 28419285
TI - Genomic differentiation and demographic histories of Atlantic and Indo-Pacific
yellowfin tuna (Thunnus albacares) populations.
AB - Recent developments in the field of genomics have provided new and powerful
insights into population structure and dynamics that are essential for the
conservation of biological diversity. As a commercially highly valuable species,
the yellowfin tuna (Thunnus albacares) is intensely exploited throughout its
distribution in tropical oceans around the world, and is currently classified as
near threatened. However, conservation efforts for this species have so far been
hampered by limited knowledge of its population structure, due to incongruent
results of previous investigations. Here, we use whole-genome sequencing in
concert with a draft genome assembly to decipher the global population structure
of the yellowfin tuna, and to investigate its demographic history. We detect
significant differentiation of Atlantic and Indo-Pacific yellowfin tuna
populations as well as the possibility of a third diverged yellowfin tuna group
in the Arabian Sea. We further observe evidence for past population expansion as
well as asymmetric gene flow from the Indo-Pacific to the Atlantic.
PMID- 28419286
TI - Horizontal inequity in outpatient care use and untreated morbidity: evidence from
nationwide surveys in India between 1995 and 2014.
AB - Equity in healthcare has been a long-term guiding principle of health policy in
India. We estimate the change in horizontal inequities in healthcare use over two
decades comparing the older population (60 years or more) with the younger
population (under 60 years). We used data from the nationwide healthcare surveys
conducted in India by the National Sample Survey Organization in 1995-96 and 2014
with sample sizes 633 405 and 335 499, respectively. Bivariate and multivariate
logit regression analyses were used to study the socioeconomic differentials in
self-reported morbidity (SRM), outpatient care and untreated morbidity.
Deviations in the degree to which healthcare was distributed according to need
were measured by horizontal inequity index (HI). In each consumption quintile the
older population had four times higher SRM and outpatient care rate than the
younger population in 2014. In 1995-96, the pro-rich inequity in outpatient care
was higher for the older (HI: 0.085; 95% CI: 0.066, 0.103) than the younger
population (0.039; 0.034, 0.043), but by 2014 this inequity became similar.
Untreated morbidity was concentrated among the poor; more so for the older (
0.320; -0.391, -0.249) than the younger (-0.176; -0.211, -0.141) population in
2014. The use of public facilities increased most in the poorest and poor
quintiles; the increase was higher for the older than the younger population in
the poorest (1.19 times) and poor (1.71 times) quintiles. The use of public
facilities was disproportionately higher for the poor in 2014 than in 1995-96 for
the older (-0.189; -0.234, -0.145 vs - 0.065; -0.129, -0.001) and the younger (
0.145; -0.175, -0.115 vs - 0.056; -0.086, -0.026) population. The older
population has much higher morbidity and is often more disadvantaged in obtaining
treatment. Health policy in India should pay special attention to equity in
access to healthcare for the older population.
PMID- 28419287
TI - Prediction Algorithm for Surgical Intervention in Neonatal Brachial Plexus Palsy.
AB - BACKGROUND: Neonatal brachial plexus palsy (NBPP) results in reduced function of
the affected arm with profound ramifications on quality of life. Advances in
surgical technique have shown improvements in outcomes for appropriately selected
patients. Patient selection, however, remains difficult. OBJECTIVE: To develop a
decision algorithm that could be applied at the individual patient level, early
in life, to reliably predict persistent NBPP that would benefit from surgery.
METHODS: Retrospective review of NBPP patients was undertaken. Maternal and
neonatal factors were entered into the C5.0 statistical package in R (The R
Foundation). A 60/40 model was employed, whereby 60% of randomized data were used
to train the decision tree, while the remaining 40% were used to test the
decision tree. The outcome of interest for the decision tree was a severe lesion
meeting requirements for surgical candidacy. RESULTS: A decision tree prediction
algorithm was generated from the entered variables. Variables utilized in the
final decision tree included presence of Horner's syndrome, presence of a
pseudomeningocele, Narakas grade, clavicle fracture at birth, birth weight >9
lbs, and induction or augmentation of labor. Sensitivity of the decision tree was
0.71, specificity 0.96, positive predictive value 0.94, negative predictive value
0.79, and F1 score 0.81. CONCLUSION: We developed a decision tree prediction
algorithm that can be applied shortly after birth to determine surgical candidacy
of patients with NBPP, the first of its kind utilizing only maternal and neonatal
factors. This conservative decision tree can be used to offer early surgical
intervention for appropriate candidates.
PMID- 28419288
TI - Editor's Note: Transitions at the JNEN.
PMID- 28419289
TI - Parkinson's disease: patient and general practitioner perspectives on the role of
primary care.
AB - Background: Specialized Parkinson's disease (PD) care offers advantages to
patients. However, specialized health care providers may be unaware of patients'
personal context and comorbidity, leading to conflicting treatment regimens.
Patients may benefit from a more holistic approach. Objective: To clarify the
role community-dwelling PD patients see for general practitioners (GPs) in PD
care and to clarify the role GPs see for themselves. Methods: Qualitative
interview study with 16 community-dwelling PD patients and 12 GPs in the
Netherlands, using a constant comparative approach to analysis. Results: Patients
expressed a preference for self-management and autonomy in decision-making. GPs
chose a limited, reactive position in early-stage PD care to stimulate patient
autonomy. Moreover, GPs felt insufficiently competent to extend their role.
Patients also felt GPs lack expert knowledge and skills; they focus on their
neurologist for PD care. In addition, GPs observed patients might not realize
what accessory role the GP could have, a role GPs described as essential in being
aware of patient's well-being. Patients did not describe additional roles for the
GP in more advanced disease, whereas GPs mentioned a shift towards a more
proactive and extended role. Conclusion: Patients and GPs see a limited role for
the GP in early-stage PD care because of patient autonomy and GP's lack of
specific knowledge and skills. However, GPs should feel more confident of the
added value of their generalist approach to care for patients with a complex
chronic disorder as PD. If generalist and specialized care reinforce each other,
PD patients benefit.
PMID- 28419290
TI - SVMQA: support-vector-machine-based protein single-model quality assessment.
AB - Motivation: The accurate ranking of predicted structural models and selecting the
best model from a given candidate pool remain as open problems in the field of
structural bioinformatics. The quality assessment (QA) methods used to address
these problems can be grouped into two categories: consensus methods and single
model methods. Consensus methods in general perform better and attain higher
correlation between predicted and true quality measures. However, these methods
frequently fail to generate proper quality scores for native-like structures
which are distinct from the rest of the pool. Conversely, single-model methods do
not suffer from this drawback and are better suited for real-life applications
where many models from various sources may not be readily available. Results: In
this study, we developed a support-vector-machine-based single-model global
quality assessment (SVMQA) method. For a given protein model, the SVMQA method
predicts TM-score and GDT_TS score based on a feature vector containing
statistical potential energy terms and consistency-based terms between the actual
structural features (extracted from the three-dimensional coordinates) and
predicted values (from primary sequence). We trained SVMQA using CASP8, CASP9 and
CASP10 targets and determined the machine parameters by 10-fold cross-validation.
We evaluated the performance of our SVMQA method on various benchmarking
datasets. Results show that SVMQA outperformed the existing best single-model QA
methods both in ranking provided protein models and in selecting the best model
from the pool. According to the CASP12 assessment, SVMQA was the best method in
selecting good-quality models from decoys in terms of GDTloss. Availability and
implementation: SVMQA method can be freely downloaded from
http://lee.kias.re.kr/SVMQA/SVMQA_eval.tar.gz. Contact: jlee@kias.re.kr.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28419291
TI - From systemic and pulmonary hypertension to heart failure: novel drugs and
devices.
PMID- 28419292
TI - Design and Testing of 2 Novel Scores That Predict Global Sagittal Alignment
Utilizing Cervical or Lumbar Plain Radiographs.
AB - BACKGROUND: Global sagittal deformity is an established cause of disability.
However, measurements of sagittal alignment are often ignored when patients
present with symptoms localizing to the cervical or lumbar spine. OBJECTIVE: To
develop scoring scales to predict the risk of sagittal malalignment in patients
with only cervical or lumbar spine radiographs. METHODS: A retrospective review
of a prospectively maintained multicenter adult spinal deformity database was
performed. Primary outcome (sagittal malalignment) was defined as a C7 plumbline
>= 50 mm. Two multivariate logistic regressions were performed using patient
characteristics and measurements derived from cervical or lumbar radiographs as
covariates. Point scores were assigned to age, body mass index (BMI), and lumbar
lordosis or T1 slope by rounding their beta coefficients to the nearest integer.
RESULTS: Nine hundred seventy-nine patients were included, with 652 randomly
assigned to the derivation cohort (used to build the score) and 327 comprising
the validation set. Final cervical score for the primary outcome included BMI >=
25 (1 point), age >= 55 yr (2 points), and T1 slope >= 27o (2 points). Final
lumbar score for the primary outcome included BMI >= 25 (1 point), age >= 55 yr
(1 point), and lumbar lordosis >= 45o (-1 points). High scores for both the
cervical and lumbar spine presented with high specificity and positive likelihood
ratios of sagittal malalignment. CONCLUSION: We developed scoring scales to
predict global sagittal malalignment utilizing clinical covariates and cervical
or lumbar radiographs. Patients with high scores may prompt imaging with long
cassette plain films to evaluate for global sagittal imbalance.
PMID- 28419293
TI - Expression and Enzyme Activity of Catalase in Chilo suppressalis (Lepidoptera:
Crambidae) Is Responsive to Environmental Stresses.
AB - Catalase (CAT) is an important antioxidant enzyme that protects organisms against
oxidative stresses by eliminating hydrogen peroxide. In this study, we cloned and
characterized a full-length cDNA of CAT from Chilo suppressalis (CsCAT) and
examined the influence of environmental stresses on CsCAT expression and enzyme
activity. The cDNA contains a 1659-bp open reading frame encoding a polypeptide
of 553 amino acids most closely related (90.14%) to Papilio polytes catalases.
The CsCAT was expressed in all developmental stages with the highest expression
in the fat body, and the CsCAT enzyme activity closely mirrored its observed mRNA
expression patterns. The CsCAT mRNA was up-regulated when the larvae were exposed
to high temperature (>=30 degrees C), insecticides (abamectin and
chlorantraniliprole), chemicals (H2O2, CHP, CdCl2, and CuSO4), and a dead-end
trap plant (vetiver grass), and the CsCAT enzyme activity again mirrored the
observed CsCAT expression patterns. These results suggest that up-regulation of
CsCAT may enhance the defense response of C. suppressalis by weakening the
effects of environmental stresses, and provide insight into the role of CsCAT
during development of C. suppressalis.
PMID- 28419294
TI - Preliminary Study of Tirofiban Infusion in Coil Embolization of Ruptured
Intracranial Aneurysms.
AB - BACKGROUND: There have been some reports on the use of intra-arterial tirofiban
in ruptured intracranial aneurysms, but few studies have reported on the use of
24 h of intravenous tirofiban infusion in patients with subarachnoid hemorrhage.
OBJECTIVE: To present our experience with intravenous tirofiban infusion, in the
form of a monotherapy as well as in addition to intra-arterial tirofiban, as a
prophylactic, and as a rescue management for thrombus in patients who have
undergone embolization with coils for ruptured intracranial aneurysms. METHODS:
Between December 2008 and January 2015, we retrospectively reviewed 249 ruptured
intracranial aneurysms that were treated with coiling at our institutions. A
total of 28 patients harboring 28 ruptured and 3 unruptured intracranial
aneurysms underwent intravenous tirofiban infusion during or after coil
embolization of an aneurysm. Intra-arterial infusion of tirofiban via a
microcatheter was also performed in 26 patients. RESULTS: Thromboembolic
formation during the procedure was detected in 25 cases. Intra-arterial tirofiban
dissolved the thromboembolus under angiographic control after 10 or more minutes
in 19 (76%) of 25 patients. Two intracranial hemorrhagic complications (increase
in the extent of hematoma) occurred during the follow-up period. Two cases of
other complications occurred: hematuria and perioral bleeding. CONCLUSION:
Intravenous tirofiban, as a monotherapy or in addition to intra-arterial
tirofiban for thrombotic complications, seems to be useful as a treatment for
acute aneurysm. However, alternatives to tirofiban should be considered if an
associated hematoma is discovered before a patient receives a tirofiban infusion.
PMID- 28419295
TI - Anatomic Features of Paraclinoid Aneurysms: Computed Tomography Angiography Study
of 144 Aneurysms in 136 Consecutive Patients.
AB - BACKGROUND: Paraclinoid aneurysms are among the most challenging aneurysms to
treat. Computed tomography (CT) angiography helps in evaluating the radiological
characteristics of these aneurysms next to bony structures. OBJECTIVE: To present
the CT angiography characteristics of paraclinoid aneurysms in order to better
understand such pathology. METHODS: The study examined CT angiography-based
anatomical characteristics obtained retrospectively from 136 patients with 144
paraclinoid aneurysms selected from single-defined catchment populations in
Finland. We examined the diameters of the parent artery (internal carotid
artery), the location of the aneurysm, its dimensions (width, height, neck), and
aneurysm wall irregularity. RESULTS: We analyzed 144 paraclinoid aneurysms in 136
patients admitted to the hospital during 2000-2014. Multivariable analysis
reveals that rupture aneurysms have the following radiological features: aneurysm
larger than 5 mm in diameter (P = .006), irregular wall (P = .046), superior
location, larger aspect ratio (P = .039), and neck wider than parent artery (P <
.001). CONCLUSION: Smaller diameter of the internal carotid artery and superior
location, as well as a large and irregular aneurysm wall, are radiological
characteristics of ruptured paraclinoid aneurysms, which CT angiography can
measure easily.
PMID- 28419297
TI - Host Pore-Forming Protein Complex Neutralizes the Acidification of Endocytic
Organelles to Counteract Intracellular Pathogens.
AB - Many intracellular pathogens invade cells via endocytic organelles and have
adapted to the drop in pH along the endocytic pathway. However, the strategy by
which the host cell counteracts this pathogen adaptation remains unclear.
betagamma-CAT is an aerolysin-like pore-forming protein and trefoil factor
complex in the frog Bombina maxima. We report here that betagamma-CAT, as a host
secreted factor with an intrinsic channel-forming property, is the first example
of a molecule that actively neutralizes the acidification of endocytic organelles
to counteract Listeria monocytogenes infection. Immunodepletion of endogenous
betagamma-CAT largely impaired the control of L. monocytogenes by frog cells.
betagamma-CAT elevates the pH of L. monocytogenes-containing vacuoles to limit
the vacuole escape of L. monocytogenes to cytosol. Furthermore, betagamma-CAT
promotes intracellular L. monocytogenes clearance via autophagy and by that the
nonlytic expulsion of the bacteria from host cells. Finally, betagamma-CAT
attenuated the dissemination of L. monocytogenes in vivo. These findings reveal a
novel host strategy and effectors that combat pathogen adaptation to acidic
conditions along the endocytic pathway.
PMID- 28419296
TI - Urinary podocyte and TGF-beta1 mRNA as markers for disease activity and
progression in anti-glomerular basement membrane nephritis.
AB - Background: Podocyte depletion causes glomerulosclerosis, with persistent
podocyte loss being a major factor driving disease progression. Urinary podocyte
mRNA is potentially useful for monitoring disease progression in both animal
models and in humans. To determine whether the same principles apply to
crescentic glomerular injury, a rat model of anti-glomerular basement membrane
(anti-GBM) nephritis was studied in parallel with a patient with anti-GBM
nephritis. Methods: Podocyte loss was measured by Wilms' Tumor 1-positive
podocyte nuclear counting and density, glomerular epithelial protein 1 or
synaptopodin-positive podocyte tuft area and urinary podocyte mRNA excretion
rate. Glomerulosclerosis was evaluated by Azan staining and urinary transforming
growth factor (TGF)-beta1 mRNA excretion rate. Results: In the rat model,
sequential kidney biopsies revealed that after a threshold of 30% podocyte loss,
the degree of glomerulosclerosis was linearly associated with the degree of
podocyte depletion, compatible with podocyte depletion driving the sclerotic
process. Urinary podocyte mRNA correlated with the rate of glomerular podocyte
loss. In treatment studies, steroids prevented glomerulosclerosis in the anti-GBM
model in contrast to angiotensin II inhibition, which lacked a protective effect,
and urinary podocyte and TGF-beta1 mRNA markers more accurately reflected both
the amount of podocyte depletion and the degree of glomerulosclerosis compared
with proteinuria under both scenarios. In a patient successfully treated for anti
GBM nephritis, urinary podocyte and TGB-beta1 mRNA reflected treatment efficacy.
Conclusion: These results emphasize the role of podocyte depletion in anti-GBM
nephritis and suggest that urinary podocyte and TGF-beta1 mRNA could serve as
markers of disease progression and treatment efficacy.
PMID- 28419298
TI - Cardiac autotransplantation for repair of left ventricular rupture after mitral
valve replacement.
AB - Left ventricular rupture is an infrequent but potentially fatal complication of
mitral valve replacement. Here, we report a case of large posterior mid
ventricular rupture following mitral valve replacement, which was successfully
treated by a sandwich style repair and autotransplantation.
PMID- 28419299
TI - Pregnancy and Labor Complications in Female Survivors of Childhood Cancer: The
British Childhood Cancer Survivor Study.
AB - Background: Female survivors of childhood cancer treated with abdominal
radiotherapy who manage to conceive are at risk of delivering premature and low
birthweight offspring, but little is known about whether abdominal radiotherapy
may also be associated with additional complications during pregnancy and labor.
We investigated the risk of developing pregnancy and labor complications among
female survivors of childhood cancer in the British Childhood Cancer Survivor
Study (BCCSS). Methods: Pregnancy and labor complications were identified by
linking the BCCSS cohort (n = 17 980) to the Hospital Episode Statistics (HES)
for England. Relative risks (RRs) of pregnancy and labor complications were
calculated by site of radiotherapy treatment (none/abdominal/cranial/other) and
other cancer-related factors using log-binomial regression. All statistical tests
were two-sided. Results: A total of 2783 singleton pregnancies among 1712 female
survivors of childhood cancer were identified in HES. Wilms tumor survivors
treated with abdominal radiotherapy were at threefold risk of hypertension
complicating pregnancy (relative risk = 3.29, 95% confidence interval [CI] = 2.29
to 4.71), while all survivors treated with abdominal radiotherapy were at risk of
gestational diabetes mellitus (RR = 3.35, 95% CI = 1.41 to 7.93) and anemia
complicating pregnancy (RR = 2.10, 95% CI = 1.27 to 3.46) compared with survivors
treated without radiotherapy. Survivors treated without radiotherapy had similar
risks of pregnancy and labor complications as the general population, except
survivors were more likely to opt for an elective cesarean section (RR = 1.39,
95% CI = 1.16 to 1.70). Conclusions: Treatment with abdominal radiotherapy
increases the risk of developing hypertension complicating pregnancy in Wilms
tumor survivors, and diabetes mellitus and anemia complicating pregnancy in all
survivors. These patients may require extra vigilance during pregnancy.
PMID- 28419300
TI - Short-term mechanical circulatory support for cardiogenic shock in severe
peripartum cardiomyopathy: La Pitie-Salpetriere experience.
AB - OBJECTIVES: Mechanical circulatory support (MCS) is a valuable option in the
setting of cardiogenic shock (CS), although MCS use in severe forms of peripartum
cardiomyopathy (PPCM) is underreported. We aimed to investigate maternal outcomes
under MCS for refractory CS complicating PPCM. METHODS: We retrospectively
reviewed 10 consecutive patients (2010-2015) meeting diagnosis criteria of PPCM
that were managed with peripheral veno-arterial extracorporeal membrane
oxygenation (pVA-ECMO) for severe CS. RESULTS: Median age was 29 years (range 20
36), and median left ventricular (LV) ejection fraction was 10% (range 5-30). All
patients received femoro-femoral cannulation. All patients were implanted after
delivery. Central rescue cannulation was considered in 5 patients in the setting
of peripheral ECMO-related complications. Median peripheral support duration was
4 days (range 2-25), median central support duration was 51 days (range 9-180).
Five patients died under central support. Three patients were successfully
explanted after LV recovery, and 2 were successfully transplanted. CONCLUSIONS:
Peripheral VA-ECMO, and prompt conversion to central rescue cannulation when
necessary have to be considered in the management of severe cases of PPCM.
Nevertheless, refractory CS in this specific population remains a life
threatening condition despite aggressive management.
PMID- 28419301
TI - Nitrogen use efficiency in crops: lessons from Arabidopsis and rice.
AB - Application of chemical fertilizers, especially nitrogen (N), to crops has
increased dramatically in the last half century and therefore developing crop
varieties with improved N use efficiency (NUE) is urgent for sustainable
agriculture. N utilization procedures generally can be divided into uptake,
transport, and assimilation. Transporters for nitrate or ammonium acquisition and
enzymes for assimilation are among the essential components determining NUE, and
many transcription factors also play a pivotal role in regulating N use
associated genes, thereby contributing to NUE. Although some efforts in improving
NUE have been made in various plants, the regulatory mechanisms underlying NUE
are still elusive, and NUE improvement in crop breeding is very limited. In this
review, the crucial components involved in N utilization and the candidates with
the potential for NUE improvement in dicot Arabidopsis and monocot rice are
summarized. In addition, strategies based on new techniques which can be used for
dissecting regulatory mechanisms of NUE and also the possible ways in which NUE
can be improved in crops are discussed.
PMID- 28419302
TI - The Posthuman as Hollow Idol: A Nietzschean Critique of Human Enhancement.
AB - In this paper, the author aims to show that transhumanists are confused about
their own conception of the posthuman: transhumanists anticipate radical
transformation of the human through technology and at the same time assume that
the criteria to determine what is "normal" and what is "enhanced" are univocal,
both in our present time and in the future. Inspired by Nietzsche's notion of the
Overhuman, the author argues that the slightest "historical and phenomenological
sense" discloses copious variations of criteria, both diachronic and synchronic,
for what can be considered "normal" and "enhanced." Radical transformation
through technology does not simply enable us to become "stronger," "smarter," or
"healthier," but it can and often will also change the very standard or yardstick
with which we measure what counts as "stronger," "smarter," or "healthier." Put
yet differently: new and emerging technologies are not neutral means but often
bring about different and, from our current perspective, foreign standards for
determining what are "normal" and "enhanced" capacities. Since the qualitative
meanings of these terms are themselves not fixed, it is unintelligible and too
reassuring to simply predict that new technologies will enhance human beings.
PMID- 28419304
TI - Incorporating a Modified Graeb Score to the Modified Fisher Scale for Improved
Risk Prediction of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid
Hemorrhage.
AB - BACKGROUND: Delayed cerebral ischemia (DCI) is a cause of poor outcome after
aneurysmal subarachnoid hemorrhage. Risk scales to predict DCI have scarcely been
evaluated for predictive accuracy. Accounting for volume of intraventricular
hemorrhage (IVH) in the modified Fischer scale (mFS) may improve its predictive
accuracy. OBJECTIVE: To compare the modified Graeb score (mGS) to the mFS for
risk prediction of DCI, and to investigate whether incorporating an mGS cut-point
into the mFS could improve predictive accuracy. METHODS: This retrospective
analysis was based on the Clazosentan to Overcome Neurological Ischemia and
Infarction Occurring after Subarachnoid Hemorrhage (CONSCIOUS-1) trial cohort.
IVH volume was quantified with the mGS. The relation of the mGS to DCI was
evaluated using logistic regression and the area under the receiver operator
characteristics curve (AUC). An optimized mGS cut-point was identified using the
Youden index, and was incorporated into the mFS to dichotomize grades 2 and 4.
The AUC was used to compare the predictive performance of the mGS with that of
the mFS, and to assess whether there was an improvement in DCI prediction after
creation of the dichotomized scale. RESULTS: The mFS and the mGS had similar
discrimination for DCI (AUC: 0.608 vs 0.618; P = .79). A new scale including both
the mFS and mGS significantly improved the AUC compared to the mFS (AUC: 0.647 vs
0.608; P = .022). CONCLUSION: The mFS and the mGS have similar prognostic
utility. Accounting for IVH volume improved prediction of DCI by the mFS.
PMID- 28419303
TI - Tumor microtubes convey resistance to surgical lesions and chemotherapy in
gliomas.
AB - Background: Primary and adaptive resistance against chemo- and radiotherapy and
local recurrence after surgery limit the benefits from these standard treatments
in glioma patients. Recently we found that glioma cells can extend ultra-long
membrane protrusions, "tumor microtubes" (TMs), for brain invasion,
proliferation, and interconnection of single cells to a syncytium that is
resistant to radiotherapy. We wondered whether TMs also convey resistance to the
other 2 standard treatment modalities. Methods: Patient-derived glioblastoma
stemlike cell (GBMSC) lines were implanted under a cranial window in mice.
Longitudinal in vivo two-photon laser scanning microscopy was used to follow
tumor growth, including the fate of single glioma cells over months. Results:
After a cylindrical surgical lesion, GBMSCs increasingly extended TMs toward the
lesion area, which contributed to the repopulation of this area over many weeks.
In fact, an excessive "healing response" was observed in which tumor cell
densities significantly exceeded those of unlesioned brain regions over time.
Inhibition of TM formation and function by genetic targeting of growth associated
protein-43 robustly suppressed this surgery-induced tumor growth reaction, in
contrast to standard postsurgical anti-inflammatory treatment with dexamethasone.
After one cycle of temozolomide chemotherapy, intra- and intertumoral
heterogeneity of TM formation and interconnection was strongly associated with
therapy response: when tumor cells were integrated in TM networks, they were more
likely to resist chemotherapy. Conclusion: TMs can contribute to the resistance
against standard treatment modalities in gliomas. Specific inhibition of TMs is a
promising approach to reduce local recurrence after surgery and lower resistance
to chemotherapy.
PMID- 28419305
TI - Selection for juvenile body weight in chickens: Standardizing for scaling.
AB - The influence of scaling on phenotypic responses to long-term selection was
evaluated in lines of chickens selected for high (HWS) and low (LWS) 8-week body
weight. The focus of the experiment was on phenotypic correlations between means
and standard deviations, and unadjusted vs. standardized responses. Traits
measured were body weight at 4 (BW4) and 8 wk (BW8). Correlations between means
and standard deviations for BW8 (the selected trait) were positive and greater
for BW4 in LWS than HWS. In both lines, scaling masked the degree more than the
pattern of response; however, after standardization, it was greater in LWS than
HWS. Selection changed the standard deviation units of juvenile BW with a 2-fold
difference in BW8 for both HWS and LWS in which the latter reached a
physiological limit. Standardization is a robust method to adjust for scaling,
thus enhancing the interpretability of responses in long-term selection
experiments. Because of changes in variances associated with those in phenotypic
means, this method to correct for part-whole correlations was useful.
PMID- 28419306
TI - Metformin and cancer in type 2 diabetes: a systematic review and comprehensive
bias evaluation.
PMID- 28419307
TI - Truth or Spin? Disease Definition in Cancer Screening.
AB - Are the small and indolent cancers found in abundance in cancer screening normal
variations, risk factors, or disease? Naturalists in philosophy of medicine turn
to pathophysiological findings to decide such questions objectively. To
understand the role of pathophysiological findings in disease definition, we must
understand how they mislead in diagnostic reasoning. Participants on all sides of
the definition of disease debate attempt to secure objectivity via reductionism.
These reductivist routes to objectivity are inconsistent with the Bayesian nature
of clinical reasoning; when they appeal to the sciences, they are inconsistent
with what philosophy of biology tells us about its natural kinds. Proposals that
we narrow the scope of our claims in the disease definition debates (proposing
adoption of a specific disease paradigm for a specific context) are useful, but
paradigms can still distort our reasoning in particular cases, even when we are
self-conscious about their status.
PMID- 28419309
TI - Influence of dietary inclusion of untreated or heat-treated Jatropha meal on
productive and reproductive performances and biochemical blood parameters of
laying Japanese quail.
AB - Jatropha meal (JM) has been characterized as a potential animal feedstuff due to
its high crude protein content and high levels of essential amino acids. However,
it contains anti-nutritive and toxic compounds that may hinder its use. The
present study was conducted to evaluate the effects of a dietary inclusion of raw
Jatropha meal (RJM) and heat-treated Jatropha meal on the growth and production
of laying Japanese quail using productive, reproductive, and biochemical blood
parameters. A total number of 180 mature Japanese quail at 2 months of age (120
females and 60 males) was randomly divided into 4 treatment groups: control (0%
JM); 3.5% RJM; 3.5% JM heated in an oven at 100 degrees C for 24 h (JM24); and
3.5% JM heated in oven at 100 degrees C for 48 h (JM48). After 8 wk on treatment
diets, the inclusion of RJM to quail diets reduced (P < 0.05) feed intake, feed
efficiency, egg number, and egg mass compared with the control diet. There was no
difference between the heat-treated Jatropha (JM24 and JM48) treatments and the
control. Fertility and hatchability percentages were improved (P < 0.001) with
JM24 and JM48 compared with the RJM group. Feeding of 3.5% RJM or JM24 in quail
diets led to significant decrease (P < 0.05) in serum total protein, albumen,
globulin, gamma-glutamyl transpeptidase, total and HDL-cholesterol,
immunoglobulin (IgG and IgM), and increased serum alanine transaminase (ALT) and
creatinine along with the mortality rate when compared with birds fed JM48. In
conclusion, heat treatment of JM is essential to eliminate its hepatotoxic and
nephrotoxic effects and, when properly heat-treated, can be used in laying
Japanese quail diets without detrimental effects on production, reproductive
performance, and health status.
PMID- 28419308
TI - Brain invasion in meningiomas-clinical considerations and impact of
neuropathological evaluation: a systematic review.
AB - With the release of the 2016 edition of the World Health Organization (WHO)
Classification of Central Nervous System Tumors, brain invasion in meningiomas
has been added as a stand-alone criterion for atypia and can therefore impact
grading and indirectly adjuvant therapy. Regarding this rising clinical
importance, we have reviewed the current knowledge about brain invasion with
emphasis on its implications on current and future clinical practice. We found
various definitions of brain invasion and approaches for evaluation in surgically
obtained specimens described over the past decades. This heterogeneity is
reflected by weak correlation with prognosis and remains controversial.
Similarly, associated clinical factors are largely unknown. Preoperative, imaging
guided detection of brain invasion is unspecific, and intraoperative assessment
using standard and new high-magnification microscopic techniques remains
imprecise. Despite the increasing knowledge about molecular alterations of the
tumor/ brain surface, pharmacotherapeutic options targeting brain invasive
meningiomas are lacking. Finally, we summarize the impact of brain invasion on
histopathological grading in the WHO classifications of brain tumors since
1979.In conclusion, standardized neurosurgical sampling and neuropathological
analyses could improve diagnostic reliability and reproducibility of future
studies. Further research is needed to improve pre- and intraoperative
visualization of brain invasion and to develop adjuvant, targeted therapies.
PMID- 28419310
TI - Calmodulin as a Ca2+-Sensing Subunit of Arabidopsis Cyclic Nucleotide-Gated
Channel Complexes.
AB - Ca2+ serves as a universal second messenger in eukaryotic signaling pathways, and
the spatial and temporal patterns of Ca2+ concentration changes are determined by
feedback and feed-forward regulation of the involved transport proteins. Cyclic
nucleotide-gated channels (CNGCs) are Ca2+-permeable channels that interact with
the ubiquitous Ca2+ sensor calmodulin (CaM). CNGCs interact with CaMs via diverse
CaM-binding sites, including an IQ-motif, which has been identified in the C
termini of CNGC20 and CNGC12. Here we present a family-wide analysis of the IQ
motif from all 20 Arabidopsis CNGC isoforms. While most of their IQ-peptides
interacted with conserved CaMs in yeast, some were unable to do so, despite high
sequence conservation across the family. We showed that the CaM binding ability
of the IQ-motif is highly dependent on its proximal and distal vicinity. We
determined that two alanine residues positioned N-terminal to the core IQ
sequence play a significant role in CaM binding, and identified a polymorphism at
this site that promoted or inhibited CaM binding in yeast. Through detailed
biophysical analysis of the CNGC2 IQ-motif, we found that this polymorphism
specifically affected the Ca2+-independent interactions with the C-lobe of CaM.
This same polymorphism partially suppressed the induction of programmed cell
death by CNGC11/12 in planta. Our work expands the model of CNGC regulation, and
posits that the C-lobe of apo-CaM is permanently associated with the channel at
the N-terminal part of the IQ-domain. This mode allows CaM to function as a Ca2+
sensing regulatory subunit of the channel complex, providing a mechanism by which
Ca2+ signals may be fine-tuned.
PMID- 28419311
TI - In Reply: Carotid Artery Angioplasty and Stenting Without Distal Embolic
Protection Devices.
PMID- 28419312
TI - Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the
Fusion Rates. What is the Optimal Graft Material?
AB - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)
is an increasingly popular procedure with several potential advantages over
traditional open TLIF. OBJECTIVE: The current study aimed to compare fusion rates
of different graft materials used in MIS-TLIF, via meta-analysis of the published
literature. METHODS: A Medline search was performed and a database was created
including patient's type of graft, clinical outcome, fusion rate, fusion
assessment modality, and duration of follow-up. Meta-analysis of the fusion rate
was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United
Kingdom). RESULTS: A total of 1533 patients from 40 series were included. Fusion
rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess
fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all
recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP
series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion
rate was seen with isolated use of autologous local bone (91.8%). The highest
fusion rate was observed with combination of autologous local bone with bone
extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was
seen with autologous local bone + bone extender (93.1%). The reported
complication rate ranged from 0% to 35.71%. Clinical improvement was observed in
all studies. CONCLUSION: Fusion rates are generally high with MIS-TLIF regardless
of the graft material used. Given the potential complications of iliac bone
harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable.
The highest fusion rate without the use of rhBMP was seen with autologous local
bone plus bone extender (93.1%).
PMID- 28419313
TI - Association between month of birth and melanoma risk: fact or fiction?
PMID- 28419314
TI - Adverse drug reactions during drug-resistant TB treatment in high HIV prevalence
settings: a systematic review and meta-analysis.
AB - Objectives: To estimate the prevalence of adverse drug reactions or events (ADR)
during drug-resistant TB (DR-TB) treatment in the context of settings with high
HIV prevalence (at least 20% of patients). Methods: We conducted a systematic
review and meta-analysis of articles in PubMed and Scopus. Pooled proportions of
patients experiencing adverse events and relative risk with 95% CI were
calculated. Results: The search yielded 24 studies, all observational cohorts.
Ten reported on the number of patients experiencing ADR and were included in the
meta-analysis representing 2776 study participants of whom 1943 were known to be
HIV infected (70.0%). An average of 83% (95% CI: 82%-84%) of patients experienced
one or more ADR. Among the seven articles ( n = 664 study participants) with
information on occurrence of severe ADR, 24% (95% CI: 21%-27%) of patients
experienced at least one severe ADR during drug-resistant TB treatment. Sixteen
of the 24 studies analysed the relative risk of ADR by HIV infection, nine of
which found no statistically significant association between HIV infection and
occurrence of drug-related ADR. There was insufficient information to
disaggregate risk by concomitant treatment with HIV antiretrovirals or by
immunosuppression (CD4 count). Conclusions: No randomized clinical trials were
found for WHO-recommended treatment of drug-resistant TB treatment where at least
20% of the cohort was coinfected with HIV. Nearly all patients (83%) experience
ADR during DR-TB treatment. While no significant association between ADR and HIV
coinfection was found, further research is needed to determine whether
concomitant antiretrovirals or immunosuppression increases the risks for HIV
infected patients.
PMID- 28419315
TI - Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as
Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in
Indonesia.
AB - Background: Damaging inflammation is thought to contribute to the high morbidity
and mortality of tuberculous meningitis (TBM), but the link between inflammation
and outcome remains unclear. Methods: We performed prospective clinical and
routine laboratory analyses of a cohort of adult patients with TBM in Indonesia.
We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal
fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM.
Patients were followed for >1 year. Results: We included 608 patients with TBM,
of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe
(ie, grade II or III) disease. One-year mortality was 43.7% and strongly
associated with decreased consciousness, fever, and focal neurological signs.
Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was
associated with higher mortality and different CSF characteristics, compared with
absence of HIV infection. Among HIV-uninfected patients, mortality was associated
with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95%
confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16
per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI,
1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95%
CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear
cell count but not with mortality (P = .915). Conclusions: A strong neutrophil
response and fever may contribute to or be a result of (immuno)pathology in TBM.
Aggressive fever control might improve outcome, and more-precise characterization
of CSF leukocytes could guide possible host-directed therapeutic strategies in
TBM.
PMID- 28419316
TI - Effects of Heat Shock on the Bradysia odoriphaga (Diptera: Sciaridae).
AB - Bradysia odoriphaga is frequently subjected to heat shock during the summer in
China. Although the effects of heat shock on insect ecology and physiology have
been widely explored, the effects of heat shock on the life history parameters of
Bradysia odoriphaga are largely unknown. In the present study, we investigated
the effects of heat shock on B. odoriphaga survival and reproduction as well as
on offspring development and sex ratio. We exposed adult B. odoriphaga to 31, 33,
35, or 37 degrees C for different durations (from 0 to 120 min). The results
showed that the survival of both sexes declined with the increase in temperature
and exposure time, especially at 33, 35, and 37 degrees C. Longevity was
markedly greater for males than females across all treatments. Fecundity
generally declined as temperature and exposure time increased, and no eggs
hatched when females were exposed to 37 degrees C for >75 min. The development
of offspring larvae was significantly delayed when the parent female and male had
been exposed to >=31 degrees C for >=30 min. In addition, the sex ratio of F1
progeny derived from heat-shocked parental adults was increasingly skewed to
female as exposure time and temperature treatment increased. Overall, the results
indicate that heat shock negatively influences B. odoriphaga.
PMID- 28419318
TI - DOUBLE-EXPONENTIAL FITTING FUNCTION FOR EVALUATION OF COSMIC-RAY-INDUCED NEUTRON
FLUENCE RATE IN ARBITRARY LOCATIONS.
AB - The fluence rate of cosmic-ray-induced neutrons (CRINs) varies with many
environmental factors. While many current simulation and experimental studies
have focused mainly on the altitude variation, the specific rule that the CRINs
vary with geomagnetic cutoff rigidity (which is related to latitude and
longitude) was not well considered. In this article, a double-exponential fitting
function F=(A1e-A2CR+A3)eB1Al, is proposed to evaluate the CRINs' fluence rate
varying with geomagnetic cutoff rigidity and altitude. The fitting R2 can have a
value up to 0.9954, and, moreover, the CRINs' fluence rate in an arbitrary
location (latitude, longitude and altitude) can be easily evaluated by the
proposed function. The field measurements of the CRINs' fluence rate and H*(10)
rate in Mt. Emei and Mt. Bowa were carried out using a FHT-762 and LB 6411
neutron prober, respectively, and the evaluation results show that the fitting
function agrees well with the measurement results.
PMID- 28419317
TI - High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized,
Multicenter Study.
AB - Context: Increase in drug frequency or dose is recommended for acromegaly
patients with partial response to long-acting somatostatin receptor ligands
(SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN
ATG) at high dose (HD) or high frequency (HF) are still scanty. Objective: To
evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients
with active acromegaly. Design: Twenty-four-week prospective, multicenter,
randomized, open-label trial. Patients and Interventions: Thirty patients with
active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21
days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Outcomes:
Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in
random growth hormone (GH) values < 1.0 ug/L, reduction in serum IGF-I and GH
from baseline, differences in biochemical response between HF and HD LAN-ATG,
adverse events. Results: IGF-I decreased significantly (P = 0.007) during the 24
week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08).
Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs
baseline), without a significant difference between HF and HD groups (P = 0.59).
The decrease in serum IGF-I significantly correlated with serum LAN values (P =
0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P =
0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19
patients (63.3%) experienced adverse events, all being mild to moderate and
transient, without differences between the two therapeutic arms. Conclusion: HF
and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one
third of patients with active acromegaly inadequately controlled by long-term
conventional SRLs therapy.
PMID- 28419319
TI - Influence of concentration, nanoparticle size, beam energy, and material on dose
enhancement in radiation therapy.
AB - The purpose of this study was to analyse the effects of the type, concentration,
and nanoparticle diameter of dose enhancement materials on the dose enhancement
of low- and high-energy megavoltage (MV) X-rays acquired from a medical linear
accelerator using Monte Carlo simulation. Monte Carlo simulation was performed
with the Monte Carlo N-Particle Transport (MCNPX) code, using the energy spectrum
of the linear accelerator and a mathematical Snyder head phantom. A 5-cm-diameter
virtual tumour was defined in the centre of the phantom. Gold, gadolinium, iodine
and iron oxide were used as dose enhancement materials. Varying concentrations
(7, 18 and 30 mg/g) of nanoparticles of different diameters (25, 50, 75, 100 and
125 nm) were applied, and the dose enhancement was comparatively evaluated for 4,
6, 10 and 15 MV X-rays, and a 60Co source. Higher dose enhancement factors (DEFs)
were observed when the incident energy was low. Moreover, the dose enhancement
effects were greatest with gold nanoparticles, followed by gadolinium, iodine,
and iron oxide nanoparticles; the DEFs were 1.011-1.047 (gold), 1.005-1.030
(gadolinium), 1.002-1.028 (iodine) and 1.002-1.014 (iron oxide). The dose
enhancement effects increased with increasing nanoparticle diameter and
concentration. However, the concentration of the material had a greater impact
than the diameter of the nanoparticles. As the concentration and diameter of
nanoparticles increased, the DEF also increased. The 4 and 6 MV X-rays
demonstrated higher dose enhancement compared with the 10 and 15 MV X-rays.
PMID- 28419320
TI - Therapeutic CPAP Level Predicts Upper Airway Collapsibility in Patients With
Obstructive Sleep Apnea.
AB - Study Objectives: Upper airway collapsibility is a key determinant of obstructive
sleep apnea (OSA) which can influence the efficacy of certain non-continuous
positive airway pressure (CPAP) treatments for OSA. However, there is no simple
way to measure this variable clinically. The present study aimed to develop a
clinically implementable tool to evaluate the collapsibility of a patient's upper
airway. Methods: Collapsibility, as characterized by the passive pharyngeal
critical closing pressure (Pcrit), was measured in 46 patients with OSA.
Associations were investigated between Pcrit and data extracted from patient
history and routine polysomnography, including CPAP titration. Results:
Therapeutic CPAP level, demonstrated the strongest relationship to Pcrit
(r2=0.51, p < .001) of all the variables investigated including apnea-hypopnea
index, body mass index, sex, and age. Patients with a mildly collapsible upper
airway (Pcrit <= -2 cmH2O) had a lower therapeutic CPAP level (6.2 +/- 0.6 vs.
10.3 +/- 0.4 cmH2O, p < .001) compared to patients with more severe
collapsibility (Pcrit > -2 cmH2O). A therapeutic CPAP level <=8.0 cmH2O was
sensitive (89%) and specific (84%) for detecting a mildly collapsible upper
airway. When applied to the independent validation data set (n = 74), this
threshold maintained high specificity (91%) but reduced sensitivity (75%).
Conclusions: Our data demonstrate that a patient's therapeutic CPAP requirement
shares a strong predictive relationship with their Pcrit and may be used to
accurately differentiate OSA patients with mild airway collapsibility from those
with moderate-to-severe collapsibility. Although this relationship needs to be
confirmed prospectively, our findings may provide clinicians with better
understanding of an individual patient's OSA phenotype, which ultimately could
assist in determining which patients are most likely to respond to non-CPAP
therapies.
PMID- 28419321
TI - Genetic analysis of partial egg production records in Japanese quail using random
regression models.
AB - The main objectives of this study were to detect the most appropriate random
regression model (RRM) to fit the data of monthly egg production in 2 lines
(selected and control) of Japanese quail and to test the consistency of different
criteria of model choice. Data from 1,200 female Japanese quails for the first 5
months of egg production from 4 consecutive generations of an egg line selected
for egg production in the first month (EP1) was analyzed. Eight RRMs with
different orders of Legendre polynomials were compared to determine the proper
model for analysis. All criteria of model choice suggested that the adequate
model included the second-order Legendre polynomials for fixed effects, and the
third-order for additive genetic effects and permanent environmental effects.
Predictive ability of the best model was the highest among all models (rho =
0.987). According to the best model fitted to the data, estimates of heritability
were relatively low to moderate (0.10 to 0.17) showed a descending pattern from
the first to the fifth month of production. A similar pattern was observed for
permanent environmental effects with greater estimates in the first (0.36) and
second (0.23) months of production than heritability estimates. Genetic
correlations between separate production periods were higher (0.18 to 0.93) than
their phenotypic counterparts (0.15 to 0.87). The superiority of the selected
line over the control was observed through significant (P < 0.05) linear contrast
estimates. Significant (P < 0.05) estimates of covariate effect (age at sexual
maturity) showed a decreased pattern with greater impact on egg production in
earlier ages (first and second months) than later ones. A methodology based on
random regression animal models can be recommended for genetic evaluation of egg
production in Japanese quail.
PMID- 28419322
TI - DOSIMETRIC EVALUATION OF LASER-DRIVEN X-RAY AND NEUTRON SOURCES UTILIZING XG-III
PS LASER WITH PEAK POWER OF 300 TERAWATT.
AB - Current short-pulse high-intensity lasers can accelerate electrons and
proton/ions to energies of giga-electron volts. For certain advanced
applications, laser-accelerated electrons and protons are optimised for high
energy X-ray and neutron generation at the XG-III picosecond (ps) laser beamline.
These energetic X-ray and neutron beams can significantly affect radiation safety
at the facility; therefore, proper evaluation of the radiological hazards induced
by laser-driven X-ray and neutron sources is required. This study presents a
dosimetric evaluation of laser-driven X-ray and neutron sources at the XG-III ps
laser beamline. The 'source terms' of the laser-accelerated electrons and protons
are characterised utilising the particle-in-cell method and an analytical model,
respectively. The Monte Carlo code FLUKA is used to calculate prompt and residual
dose yields due to all radiation field components and the number of residual
activated nuclei. Our results can provide a reference for radiation hazard
analysis at short-pulse high-intensity laser facilities worldwide.
PMID- 28419323
TI - Monte Carlo Simulation Used to Calculate Energy Correction Factor for
Thermoluminescent Dosimeters Used by Occupational Workers on Pediatric Exams.
AB - The main objective of this work is to simulate the X-ray scattered spectra by
different pediatric phantoms (simulation of children subjected to barium meal
procedures) to calculate an energy correction factor (ECF) to the reading of
thermoluminescent dosimeters (TLDs). To perform this evaluation, the TLDs were
positioned over three areas in two occupational workers: eyes, thyroid and hands.
The Geant4 toolkit was used to define the spectra collected by TLDs, making
possible to calculate the ECF. This work was developed in two stages: (1)
evaluation of scattered spectra by different standard phantoms (newborn, 1, 5 and
10 years old); (2) definition of the ECF to the absorbed energy by each TLD.
Geant4 shows to be a good toolkit to calculate the ECF and among the different
characteristics evaluated, in this work, the TLD position and acceleration
voltages are the most significant parameters that may influence the ECF
calculated.
PMID- 28419324
TI - Improving data workflow systems with cloud services and use of open data for
bioinformatics research.
AB - Data workflow systems (DWFSs) enable bioinformatics researchers to combine
components for data access and data analytics, and to share the final data
analytics approach with their collaborators. Increasingly, such systems have to
cope with large-scale data, such as full genomes (about 200 GB each), public fact
repositories (about 100 TB of data) and 3D imaging data at even larger scales. As
moving the data becomes cumbersome, the DWFS needs to embed its processes into a
cloud infrastructure, where the data are already hosted. As the standardized
public data play an increasingly important role, the DWFS needs to comply with
Semantic Web technologies. This advancement to DWFS would reduce overhead costs
and accelerate the progress in bioinformatics research based on large-scale data
and public resources, as researchers would require less specialized IT knowledge
for the implementation. Furthermore, the high data growth rates in bioinformatics
research drive the demand for parallel and distributed computing, which then
imposes a need for scalability and high-throughput capabilities onto the DWFS. As
a result, requirements for data sharing and access to public knowledge bases
suggest that compliance of the DWFS with Semantic Web standards is necessary. In
this article, we will analyze the existing DWFS with regard to their capabilities
toward public open data use as well as large-scale computational and human
interface requirements. We untangle the parameters for selecting a preferable
solution for bioinformatics research with particular consideration to using cloud
services and Semantic Web technologies. Our analysis leads to research guidelines
and recommendations toward the development of future DWFS for the bioinformatics
research community.
PMID- 28419325
TI - Dissecting molecular and physiological response mechanisms to high solar
radiation in cyanic and acyanic leaves: a case study on red and green basil.
AB - Photosynthetic performance and the expression of genes involved in light
signaling and the biosynthesis of isoprenoids and phenylpropanoids were analysed
in green ('Tigullio', TIG) and red ('Red Rubin', RR) basil. The aim was to detect
the physiological and molecular response mechanisms to high sunlight. The
attenuation of blue-green light by epidermal anthocyanins was shown to evoke
shade-avoidance responses with consequential effects on leaf morpho-anatomical
traits and gas exchange performance. Red basil had a lower mesophyll conductance,
partially compensated by the less effective control of stomatal movements, in
comparison with TIG. Photosynthesis decreased more in TIG than in RR in high
sunlight, because of larger stomatal limitations and the transient impairment of
PSII photochemistry. The methylerythritol 4-phosphate pathway promoted above all
the synthesis and de-epoxidation of violaxanthin-cycle pigments in TIG and of
neoxanthin and lutein in RR. This enabled the green leaves to process the excess
radiant energy effectively, and the red leaves to optimize light harvesting and
photoprotection. The greater stomatal closure observed in TIG than in RR was due
to enhanced abscisic acid (ABA) glucose ester deglucosylation and reduced ABA
oxidation, rather than to superior de novo ABA synthesis. This study shows a
strong competition between anthocyanin and flavonol biosynthesis, which occurs at
the level of genes regulating the oxidation of the C2-C3 bond in the dihydro
flavonoid skeleton.
PMID- 28419326
TI - Accessibility to surgical robot technology and prostate-cancer patient behavior
for prostatectomy.
AB - Background: To examine how surgical robot emergence affects prostate-cancer
patient behavior in seeking radical prostatectomy focusing on geographical
accessibility. Methods: In Japan, robotic surgery was approved in April 2012.
Based on data in the Japanese Diagnosis Procedure Combination database between
April 2012 and March 2014, distance to nearest surgical robot and interval days
to radical prostatectomy (divided by mean interval in 2011: % interval days to
radical prostatectomy) were calculated for individual radical prostatectomy cases
at non-robotic hospitals. Caseload changes regarding distance to nearest surgical
robot and robot introduction were investigated. Change in % interval days to
radical prostatectomy was evaluated by multivariate analysis including distance
to nearest surgical robot, age, comorbidity, hospital volume, operation type,
hospital academic status, bed volume and temporal progress. Results: % Interval
days to radical prostatectomy became wider for distance to nearest surgical robot
<30 km. When a surgical robot emerged within 30 and 10 km, the prostatectomy
caseload in non-robot hospitals reduced by 13 and 18% within 6 months,
respectively, while the robot hospitals gained +101% caseload (P < 0.01 for all)
Multivariate analyses including 9759 open and 5052 non-robotic minimally invasive
radical prostatectomies in 483 non-robot hospitals revealed a significant inverse
association between distance to nearest surgical robot and % interval days to
radical prostatectomy (B = -17.3% for distance to nearest surgical robot >=30 km
and -11.7% for 10-30 km versus distance to nearest surgical robot <10 km), while
younger age, high-volume hospital, open-prostatectomy provider and temporal
progress were other significant factors related to % interval days to radical
prostatectomy widening (P < 0.05 for all). Conclusions: Robotic surgery
accessibility within 30 km would make patients less likely select conventional
surgery. The nearer a robot was, the faster the caseload reduction was.
PMID- 28419327
TI - Epilepsy Surgeries Requiring an Operculoinsular Cortectomy: Operative Technique
and Results.
AB - BACKGROUND: Epilepsy surgeries requiring an operculoinsulectomy pose significant
difficulties because the perisylvian area is highly vascular, deep, and
functional. OBJECTIVE: To report the operative technique and results of epilepsy
surgeries requiring an operculoinsular cortectomy at our institution. METHODS:
The data of all consecutive patients who had undergone an epilepsy surgery
requiring an operculoinsular cortectomy with a minimum follow-up of 1 yr were
reviewed. Tumor and vascular malformation cases were excluded. Surgical
techniques are described based on findings during surgery. RESULTS: Twenty-five
patients underwent an epilepsy surgery requiring an operculoinsular cortectomy:
mean age at surgery was 35 y (9-51), mean duration of epilepsy was 19 y (5-36),
14 were female, and mean duration of follow-up was 4.7 y (1-16). Magnetic
resonance imaging of the operculoinsular area was normal or revealed questionable
nonspecific findings in 72% of cases. Investigation with intracranial EEG
electrodes was done in 17 patients. Surgery was performed on the dominant side
for language in 7 patients. An opercular resection was performed in all but 2
patients who only had an insulectomy. Engel class I seizure control was achieved
in 80% of patients. Postoperative neurological deficits (paresis, dysphasia,
alteration of taste, smell, hearing, pain, and thermal perceptions) were frequent
(75%) but always transient except for 1 patient with persistent mild alteration
of thermal and pain perception. CONCLUSION: Surgical treatment of operculoinsular
epilepsy is effective in achieving seizure control and is associated with an
acceptable long-term complication rate.
PMID- 28419328
TI - Efficacy and safety of osimertinib in a Japanese compassionate use program.
AB - Background: Osimertinib is a third-generation epidermal growth factor receptor
(EGFR) tyrosine kinase inhibitor (TKI) that targets the T790M mutation of EGFR.
In 2016, AstraZeneca conducted a compassionate use program for osimertinib in
Japan. Methods: Eighteen consecutive patients with histologically proven non
small-cell lung cancer (NSCLC) and harboring the T790M EGFR mutation participated
in the compassionate use program between 1 April and 25 May 2016, at the National
Cancer Center Hospital. We examined the efficacy and safety of osimertinib in a
compassionate use program. Results: All patients had been previously treated with
both cytotoxic chemotherapy and EGFR TKIs. Overall response rate was 62.5% (95%
confidence interval (CI): 35.9-89.1%). Among the six patients pretreated with a
third-generation EGFR TKI, two (33%) responded to osimertinib. On administration
with osimertinib, median progression-free and overall survival rates at six
months were 66.7% (95% CI: 44.9-88.5) and 88.9% (95% CI: 74.4-100), respectively.
Although the toxicity of osimertinib was mild in most patients, three patients
had severe adverse events: two developed interstitial lung disease (ILD) and one
developed Grade 3 hepatotoxicity. Among these, two (33%) of the six patients who
received osimertinib following nivolumab treatment developed severe adverse
events, with one each developing Grade 3 hepatotoxicity and Grade 3 ILD. Only one
patient visited our hospital seeking to participate in the compassionate program
from another hospital. Conclusion: Osimertinib demonstrated efficacy even in
patients with heavily pretreated NSCLC harboring the T790M mutation. Some
patients pretreated with another third-generation EGFR TKI also responded to
osimertinib.
PMID- 28419329
TI - Effects of the inclusion of a Bacillus direct-fed microbial on performance
parameters, bone quality, recovered gut microflora, and intestinal morphology in
broilers consuming a grower diet containing corn distillers dried grains with
solubles.
AB - Distillers dried grains with solubles (DDGS) have increasingly been used in
poultry diets as a consequence of rising grain costs. Some, but not all, sources
of DDGS have a variable compositional value, and a high inclusion of this by
product could be considered a risk factor for presentation of enteric diseases.
Presently, 2 experiments were conducted using a starter corn-soybean diet (zero
to 7 d) and a corn-DDGS-soybean grower diet (8 to 28 d) with or without inclusion
of a Bacillus-direct-fed microbial (DFM). In both experiments, day-of-hatch
chicks were randomly assigned to 2 different groups: control group without DFM or
Bacillus-DFM group, containing 106 spores/g of feed. In each experiment, 8 pens
of 20 chicks (n = 160/group) were used. Performance parameters of BW, BW gain
(BWG), feed intake (FI), and feed conversion (FCR) were evaluated in each growth
phase. Additionally, in experiment 2, intestinal samples were collected to
determine duodenal and ileal morphology (n = 8/group), as well as the microbiota
population of total lactic acid bacteria (TLAB), total Gram-negative bacteria
(TGNB), and total anaerobic bacteria (TAB) on d 28 (n = 16/group). Furthermore,
both tibias were evaluated for bone strength and bone composition (n = 16/group).
In both experiments BW, BWG, and FCR were improved by the DFM when compared to
the control group (P < 0.05). In experiment 2, chickens supplemented with the DFM
had less TGNB in the foregut intestinal segment and higher TLAB counts in both
foregut and hindgut sections (P < 0.05). In addition significant increases in
tibia breaking strength and bone mineralization were observed in the DFM group
when compared with the control. In the case of intestinal morphology, DFM dietary
inclusion increased villus height (VH), villus width, villus area, muscular
thickness, and the VH to crypt depth ratio (VH:CD) in both duodenum and ileum
sections. Results of the present study suggest that consumption of a selected
Bacillus-DFM producing a variable set of enzymes could contribute to enhanced
performance, intestinal microbial balance, and bone quality in broiler chickens
consuming a grower diet that contains corn-DDGS.
PMID- 28419330
TI - Seizure Outcomes in Occipital Lobe and Posterior Quadrant Epilepsy Surgery: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Occipital lobe epilepsy (OLE) is an uncommon but debilitating focal
epilepsy syndrome with seizures often refractory to medical management. While
surgical resection has proven a viable treatment, previous studies examining
postoperative seizure freedom rates are limited by small sample size and patient
heterogeneity, thus exhibiting significant variability in their results.
OBJECTIVE: To review the medical literature on OLE so as to investigate rates and
predictors of both seizure freedom and visual outcomes following surgery.
METHODS: We reviewed manuscripts exploring surgical resection for drug-resistant
OLE published between January 1990 and June 2015 on PubMed. Seizure freedom rates
were analyzed and potential predictors were evaluated with separate meta
analyses. Postoperative visual outcomes were also examined. RESULTS: We
identified 27 case series comprising 584 patients with greater than 1 yr of
follow-up. Postoperative seizure freedom (Engel class I outcome) was observed in
65% of patients, and was significantly predicted by age less than 18 yr (odds
ratio [OR] 1.54, 95% confidence interval [CI] 1.13-2.18), focal lesion on
pathological analysis (OR 2.08, 95% CI 1.58-2.89), and abnormal preoperative
magnetic resonance imaging (OR 3.24, 95% 2.03-6.55). Of these patients, 175 also
had visual outcomes reported with 57% demonstrating some degree of visual decline
following surgery. We did not find any relationship between postoperative visual
and seizure outcomes. CONCLUSION: Surgical resection for OLE is associated with
favorable outcomes with nearly two-thirds of patients achieving postoperative
seizure freedom. However, patients must be counseled regarding the risk of visual
decline following surgery.
PMID- 28419331
TI - An Apoplastic beta-Glucosidase is Essential for the Degradation of Flavonol 3-O
beta-Glucoside-7-O-alpha-Rhamnosides in Arabidopsis.
AB - Flavonol bisglycosides accumulate in plant vegetative tissues in response to
abiotic stress, including simultaneous environmental perturbations (i.e. nitrogen
deficiency and low temperature, NDLT), but disappear with recovery from NDLT.
Previously, we determined that a recombinant Arabidopsis beta-glucosidase (BGLU),
BGLU15, hydrolyzes flavonol 3-O-beta-glucoside-7-O-alpha-rhamnosides and flavonol
3-O-beta-glucosides, forming flavonol 7-O-alpha-rhamnosides and flavonol
aglycones, respectively. In this study, the transient expression of a BGLU15
Cherry fusion protein in onion epidermal cells demonstrated that BGLU15 was
localized to the apoplast. Analysis of BGLU15 T-DNA insertional inactivation
lines (bglu15-1 and bglu15-2) revealed negligible levels of BGLU15 transcripts,
whereas its paralogs BGLU12 and BGLU16 were expressed in wild-type and bglu15
plants. The recombinant BGLU16 did not hydrolyze quercetin 3-O-beta-glucoside-7-O
alpha-rhamnoside or rhamnosylated flavonols, but was active with the synthetic
substrate, p-nitrophenyl-beta-d-glucoside. In addition, shoots of both bglu15
mutants contained negligible flavonol 3-O-beta-glucoside-7-O-alpha-rhamnoside
hydrolase activity, whereas this activity increased by 223% within 2 d of NDLT
recovery in wild-type plants. The levels of flavonol 3-O-beta-glucoside-7-O-alpha
rhamnosides and quercetin 3-O-beta-glucoside were high and relatively unchanged
in shoots of bglu15 mutants during recovery from NDLT, whereas rapid losses were
apparent in wild-type shoots. Moreover, losses of two flavonol 3-O-beta
neohesperidoside-7-O-alpha-rhamnosides and kaempferol 3-O-alpha-rhamnoside-7-O
alpha-rhamnoside were evident during recovery from NDLT, regardless of whether
BGLU15 was present. A spike in a kaempferol 7-O-alpha-rhamnoside occurred with
stress recovery, regardless of germplasm, suggesting a contribution from
hydrolysis of kaempferol 3-O-beta-neohesperidoside-7-O-alpha-rhamnosides and/or
kaempferol 3-O-alpha-rhamnoside-7-O-alpha-rhamnoside by hitherto unknown
mechanisms. Thus, BGLU15 is essential for catabolism of flavonol 3-O-beta
glucoside-7-O-alpha-rhamnosides and flavonol 3-O-beta-glucosides in Arabidopsis.
PMID- 28419332
TI - NEW MODEL FOR MINES AND TRANSPORTATION TUNNELS EXTERNAL DOSE CALCULATION USING
MONTE CARLO SIMULATION.
AB - In this work, a new methodology is developed based on Monte Carlo simulation for
tunnels and mines external dose calculation. Tunnels external dose evaluation
model of a cylindrical shape of finite thickness with an entrance and with or
without exit. A photon transportation model was applied for exposure dose
calculations. A new software based on Monte Carlo solution was designed and
programmed using Delphi programming language. The variation of external dose due
to radioactive nuclei in a mine tunnel and the corresponding experimental data
lies in the range 7.3-19.9%. The variation of specific external dose rate with
position in, tunnel building material density and composition were studied. The
given new model has more flexible for real external dose in any cylindrical
tunnel structure calculations.
PMID- 28419333
TI - Surgical resection for clinical-Stage I radiological pure-solid lung cancer that
met the current high risk criteria.
AB - Objective: We assessed whether surgical resection is acceptable for radiological
invasive non-small cell lung cancer (NSCLC) that met the current high-risk
criteria. Methods: We reviewed 500 clinical-Stage I NSCLCs with a radiological
pure-solid appearance. High-risk criterion was defined as follows: (1)
preoperative FEV1% <= 50% or DLco% <= 50%, (2) age > 75y with 50% < FEV1% < 60%
or 50% < DLco% < 60%, and (3) three or more severe general comorbidities.
Results: The high-risk group comprised 184 (37%) patients. The percentages for
elderly, male, smoker, non-adenocarcinoma histology were significantly higher
than those of the normal-risk group (P < 0.001). Lobectomy was performed in 148
(80%) patients. Overall survival (OS) was significantly worse in the high-risk
group (59.4% vs 73.1%, P = 0.004), however, a multivariate analysis revealed that
high-risk was not associated with poor survival (P = 0.519). Furthermore, there
were no significant differences between the high-risk and normal-risk groups
regarding cancer-specific survival (74.5% vs 79.2%, P = 0.569). Postoperative
morbidity rates were significantly different between the two study arms (45% vs
25%, P < 0.001), however, the 30-day and 90-day mortality rates for the high-risk
group were 1.6% and 3.8%, respectively. In the high-risk patients, the difference
in survival between lobectomy and sublobar resection was not significant (69.4%
vs 78.6%, P = 0.716), and was also proven in the propensity-score matched
patients (82.1% vs 76.0%, P = 0.623). Conclusions: Conventional high-risk
criteria are not always appropriate prognostic variables, and lung cancer
specific survival or short-term mortalities for high-risk patients were fully
acceptable. Surgical therapy including lobectomy should not be readily excluded
from radical local management even when a patient meets the high-risk criteria.
PMID- 28419335
TI - Transfer of the Sick Neonate: What Is Needed?
PMID- 28419334
TI - Effect of a low crude protein diet supplemented with different levels of
threonine on growth performance, carcass traits, blood parameters, and immune
responses of growing broilers.
AB - A study was conducted to evaluate growth performance, carcass traits, blood serum
parameters, and immune responses of Ross 308 male broilers fed diets containing 2
different crude protein (CP) levels (97.5 and 100%) and 4 threonine (Thr) levels
(100, 110, 120, and 130% of Ross recommendations for starter and grower periods).
A completely randomized block design was adopted and main effects (CP and Thr)
were arranged in a 2 * 4 factorial approach. Optimum growth performance was
achieved when broiler requirements for CP and Thr were 100% satisfied. The 110%
Thr inclusion in 97.5% CP diet increased ADG, ADFI, energy intake, and protein
intake (Thr, P < 0.01; quadratic, P = 0.01). The G:F (linear, P = 0.05) and
energy efficiency (linear, P = 0.04) tended to decreased (Thr, P = 0.09) by
increasing Thr supplementation level, whereas protein efficiency tended to
increase (CP, P = 0.06) by reducing CP level. The 110% Thr inclusion in 97.5% CP
diet increased eviscerated carcass weight (CP * Thr, P = 0.03) and carcass yield
(Thr, P = 0.08; quadratic, P = 0.05). The reduction of CP content promoted fat
abdominal deposition (CP, P = 0.05). Incremental Thr raised abdominal fat (Thr, P
= 0.01; linear, P = 0.01). The 97.5% CP diets resulted in higher serum
concentrations of uric acid (CP, P = 0.02), total and high- and low-density
lipoprotein-linked cholesterol (CP, P<= 0.01), and alanine aminotransferase (CP,
P = 0.05) and lower (CP, P = 0.01) concentrations of triglycerides and very low
density lipoproteins compared with the 100% CP diets. However, the Thr inclusion
improved serum lipid profile. Irrespective of CP content, incremental Thr levels
up to 120% increased (Thr, P = 0.01) broiler immune responses against Newcastle
disease virus and sheep red blood cells. In order to reduce dietary CP content,
strategies to increase synthetic amino acid availability, such as the use of
encapsulated amino acids, should be taken into account.
PMID- 28419336
TI - IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1+
cells via the calcineurin-NFATc3-Etv2 pathway.
AB - Ca2+ signals participate in various cellular processes with spatial and temporal
dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated
Ca2+ signals are essential for early development. However, the underlying
mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we
report that IP3Rs are required for the hematopoietic and cardiac fate divergence
of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced
Flk1+/PDGFRalpha- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor
cell population, and the colony-forming unit activity, but increased cardiac
progenitor markers as well as cardiomyocytes. Concomitantly, the expression of a
key regulator of hematopoiesis, Etv2, was reduced in IP3R-tKO cells, which could
be rescued by the activation of Ca2+ signals and calcineurin or overexpression of
constitutively active form of NFATc3. Furthermore, IP3R-tKO impaired specific
targeting of Etv2 by NFATc3 via its evolutionarily conserved cis-element in
differentiating ESCs. Importantly, the activation of Ca2+-calcineurin-NFAT
pathway reversed the phenotype of IP3R-tKO cells. These findings reveal an
unrecognized governing role of IP3Rs in hematopoietic and cardiac fate commitment
via IP3Rs-Ca2+-calcineurin-NFATc3-Etv2 pathway.
PMID- 28419338
TI - Primary angiitis of the central nervous system-a territory about to be
discovered.
PMID- 28419337
TI - Targeted Embolization of Aneurysms Associated With Brain Arteriovenous
Malformations at High Risk for Surgical Resection: A Case-Control Study.
AB - BACKGROUND: High-risk components of brain arteriovenous malformations (BAVMs) can
be targeted to reduce the risk of lesion rupture. OBJECTIVE: To evaluate targeted
embolization of aneurysms against other means of treatment with a case-control
analysis; we previously investigated this approach associated with BAVMs.
METHODS: Retrospective analysis of patients with BAVMs was performed, identifying
patients treated with intention to occlude only an aneurysm associated with a
BAVM. For each targeted aneurysm embolization (TAE) patient identified, 4 control
patients were randomly selected, controlling for rupture status, age, and
Spetzler-Martin plus Lawton-Young supplemental score. Analysis was performed to
compare rates of adverse events (hemorrhage, new seizure, and death) between the
2 groups. RESULTS: Thirty-two patients met inclusion criteria, and 128 control
patients were identified, out of 1103 patients treated during the study period.
Thirty-four adverse events occurred (15 ruptures, 15 new seizures, and 11 deaths)
during the follow-up period (mean 1157 d for the TAE cohort and 1036 d for the
non-TAE cohort). Statistically lower associations were noted for the TAE group
for any adverse event (hazard ratio 0.28, P = .037) and the composite outcome of
hemorrhage or new seizure (hazard ratio 0.20, P = .029). CONCLUSION: For BAVMs at
high risk for surgical resection, TAE can be performed safely and effectively.
Patients treated with TAE had better outcomes than matched patients undergoing
other combinations of treatment. TAE can be considered for BAVMs with high
operative risk prior to radiosurgery or when no other treatment options are
available.
PMID- 28419339
TI - Effect of chlorine treatment on inhibition of E. coli serogroup O2 incorporation
into 7-day-old biofilm on polyvinylchloride surface.
AB - Poultry waterlines are constructed using polyvinylchloride (PVC) material on
which bacterial biofilm can easily form. Biofilm can harbor pathogens including
avian pathogenic E. coli (APEC) strains. An in vitro evaluation was performed to
determine if E. coli sero group O2 (avian pathogenic) could attach on a PVC
surface that had pre-formed biofilm and if this phenomenon could be affected when
water was treated with chlorine. Initially, biofilm growth was induced in PVC
test coupons (15.16 cm2) for a 7-day period mimicking the waterline scenario in
the first wk of poultry brooding; and then this biofilm was challenged with E.
coli O2 seeded water in presence/absence of chlorine treatment. After rinsing,
test coupons were sampled for bacterial (APC) and E. coli O2 enumeration at
various occasions post seeding the pathogen and chlorine treatment. Day 7 APC
recovered from coupons was 4.35 log10 cfu/cm2 in trial 1 and 3.66 log10 cfu/cm2
in trial 2. E. coli O2 was not recovered from chlorine treated test coupons (P <
0.05), whereas it was retrieved from untreated coupons (untreated contained > 3
log10 cfu/cm2 in trial 1 and > 2 log10 cfu/cm2 in trial 2). This study suggests
that E. coli O2 can incorporate into pre-formed biofilm on a PVC surface within
24 h if water sanitation is not present, and the attachment time of the pathogen
can prolong in the absence of already formed biofilm.
PMID- 28419341
TI - Letter: Decompressive Surgery for Diabetic Neuropathy: Waiting for
Incontrovertible Proof.
PMID- 28419340
TI - Extremely thick cell walls and low mesophyll conductance: welcome to the world of
ancient living!
AB - Mesophyll conductance is thought to be an important photosynthetic limitation in
gymnosperms, but they currently constitute the most understudied plant group in
regard to the extent to which photosynthesis and intrinsic water use efficiency
are limited by mesophyll conductance. A comprehensive analysis of leaf gas
exchange, photosynthetic limitations, mesophyll conductance (calculated by three
methods previously used for across-species comparisons), and the underlying ultra
anatomical, morphological and chemical traits in 11 gymnosperm species varying in
evolutionary history was performed to gain insight into the evolution of
structural and physiological controls on photosynthesis at the lower return end
of the leaf economics spectrum. Two primitive herbaceous species were included in
order to provide greater evolutionary context. Low mesophyll conductance was the
main limiting factor of photosynthesis in the majority of species. The strongest
sources of limitation were extremely thick mesophyll cell walls, high chloroplast
thickness and variation in chloroplast shape and size, and the low exposed
surface area of chloroplasts per unit leaf area. In gymnosperms, the negative
relationship between net assimilation per mass and leaf mass per area reflected
an increased mesophyll cell wall thickness, whereas the easy-to-measure
integrative trait of leaf mass per area failed to predict the underlying
ultrastructural traits limiting mesophyll conductance.
PMID- 28419342
TI - Future Generations and the Justifiability of Germline Engineering.
AB - The possibility of performing germline modifications on currently living
individuals targets future generations' health and well-being by reducing the
diversity of the human gene pool. This can have two negative repercussions: (1)
reduction of heterozygosity, the latter being associated with a health or
performance advantage; (2) uniformization of the genes involved in reproductive
recombination, which may lead to the health risks involved in asexual
reproduction. I argue that germline interventions aimed at modifying the genomes
of future people cannot be ethically justifiable if there is no possibility of
controlling the intervention either by reversing or altering it, whenever need
demands it. This argument is challenged on six different grounds: safety,
population versus individual focus, spontaneous mutations, exceptionalism, the
intentional pursuit of genetic diversity through germline interventions, and harm
reduction potential.
PMID- 28419343
TI - Utilizing a Modified Care Coordination Measurement Tool to Capture Value for a
Pediatric Outpatient Parenteral and Prolonged Oral Antibiotic Therapy Program.
AB - Background: Outpatient parenteral or prolonged oral antibiotic therapy (OPAT)
programs reduce inpatient healthcare costs by shifting care to outpatient
settings. Care coordination (CC) is a necessary component to successfully
transition patients. Our objective was to assess outcomes of provider time spent
on nonreimbursable CC activities in a pediatric OPAT program. Methods: We used a
qualitative feasibility pilot design and modified the Care Coordination
Measurement Tool. We captured nonreimbursable CC activity and associated
outcome(s) among pediatric patients enrolled in OPAT from March 1 to April 30,
2015 (44 work days) at Doernbecher Children's Hospital. We generated summary
statistics for this institutional review board-waived QI project. Results: There
were 154 nonreimbursable CC encounters conducted by 2 infectious diseases (ID)
providers for 29 patients, ages 17 months-15 years, with complex infections.
Total estimated time spent on CC was 54 hours, equivalent to at least 6 workdays.
Five patients with complex social issues used 37% of total CC time. Of 129 phone
events, 38% involved direct contact with families, pharmacies (13%), primary care
providers (13%), and home health nursing (11%). Care coordination prevented 10
emergency room (ER) visits and 2 readmissions. Care coordination led to 16
additional, not previously scheduled subspecialist and 13 primary care visits.
The OPAT providers billed for 32 clinic visits during the study period.
Conclusions: Nonreimbursable CC work by OPAT providers prevented readmissions and
ER visits and helped facilitate appropriate healthcare use. The value of
pediatric OPAT involvement in patient care would have been underestimated based
on reimbursable ID consultations and clinic visits alone.
PMID- 28419344
TI - A Place to Grow? Host Choice and Larval Performance of Microplitis similis
(Hymenoptera: Braconidae) in the Host Spodoptera litura (Lepidoptera: Noctuidae).
AB - Host selection is a key stage in the lifecycle of parasitoids, and is critical to
both their function in control and to the maintenance of their population. The
solitary endoparasitoid Microplitis similis (Hymenoptera: Braconidae) is a
potential biological control agent of Spodoptera litura (F.) larvae (Lepidoptera:
Noctuidae). In this study, we examined the preference M. similis exhibits for
different instars of the host, host instar effects on parasitoid development, and
the weight gain and food consumption of different instars of parasitized larvae.
In no-choice tests, parasitization rates were highest in second- and early third
instar larvae, and no fourth- or fifth-instar hosts were parasitized. When
provided with a choice of first- to late third-instar host larvae, M. similis
preferred to parasitize early third-instar host larvae (41%) with a selection
coefficient of 0.37. All morphometric features of wasp offspring increased with
increasing age of the host at parasitization. A lower proportion of females
emerged from first-instar larvae than any other instar. Parasitized S. litura
larvae showed a pronounced reduction in food consumption and weight gain.
Microplitis similis may have the potential to significantly suppress population
growth and the damage caused by S. litura.
PMID- 28419345
TI - Dehydration responsive element binding transcription factors and their
applications for the engineering of stress tolerance.
AB - Dehydration responsive element binding (DREB) factors or CRT element binding
factors (CBFs) are members of the AP2/ERF family, which comprises a large number
of stress-responsive regulatory genes. This review traverses almost two decades
of research, from the discovery of DREB/CBF factors to their optimization for
application in plant biotechnology. In this review, we describe (i) the
discovery, classification, structure, and evolution of DREB genes and proteins;
(ii) induction of DREB genes by abiotic stresses and involvement of their
products in stress responses; (iii) protein structure and DNA binding selectivity
of different groups of DREB proteins; (iv) post-transcriptional and post
translational mechanisms of DREB transcription factor (TF) regulation; and (v)
physical and/or functional interaction of DREB TFs with other proteins during
plant stress responses. We also discuss existing issues in applications of DREB
TFs for engineering of enhanced stress tolerance and improved performance under
stress of transgenic crop plants.
PMID- 28419346
TI - Our Shared Vulnerability to Dangerous Pathogens.
AB - The international community vastly underestimates the risk and scale of our
shared vulnerability to fast moving pathogens. Ranging from SARS and novel
influenzas to Ebola and Zika, the world seems to be caught off guard, despite the
regularity of global health threats historically. More importantly, when
governments and international institutions underestimate the threat, they also
underinvest in preparedness. Failure to prepare has deep costs in human lives and
economic productivity. Here, I offer a pathway to preparedness for, and rapid
response to, infectious disease threats: robust and resilient national health
systems; strong institutions capable of leading, particularly the World Health
Organization; and investments in research and development. Overall, the world
needs a strong system of laws and governance, ranging from the International
Health Regulations through to norms of transparency and accountability. To secure
our common future, the world needs sustained investment and leadership. I propose
a 'security dividend', both financial and institutional, to remake the global
health security system.
PMID- 28419347
TI - Evolutionary trade-offs between drought resistance mechanisms across a
precipitation gradient in a seasonally dry tropical oak (Quercus oleoides).
AB - In seasonally dry tropical forest regions, drought avoidance during the dry
season coupled with high assimilation rates in the wet season is hypothesized to
be an advantageous strategy for forest trees in regions with severe and long dry
seasons. In contrast, where dry seasons are milder, drought tolerance coupled
with a conservative resource-use strategy is expected to maximize carbon
assimilation throughout the year. Tests of this hypothesis, particularly at the
intraspecific level, have been seldom conducted. In this study, we tested the
extent to which drought resistance mechanisms and rates of carbon assimilation
have evolved under climates with varying dry season length and severity within
Quercus oleoidesCham. and Schlect., a tropical dry forest species that is widely
distributed in Central America. For this purpose, we conducted a greenhouse
experiment where seedlings originating from five populations that vary in
rainfall patterns were grown under different watering treatments. Our results
revealed that populations from xeric climates with more severe dry seasons
exhibited large mesophyllous leaves (with high specific leaf area, SLA), and leaf
abscission in response to drought, consistent with a drought-avoidance strategy.
In contrast, populations from more mesic climates with less severe dry seasons
had small and thick sclerophyllous leaves with low SLA and reduced water
potential at the turgor loss point (pitlp), consistent with a drought-tolerance
strategy. Mesic populations also showed high plasticity in pitlp in response to
water availability, indicating that osmotic adjustment to drought is an important
component of this strategy. However, populations with mesophyllous leaves did not
have higher maximum carbon assimilation rates under well-watered conditions.
Furthermore, SLA was negatively associated with mass-based photosynthetic rates,
contrary to expectations of the leaf economics spectrum, indicating that drought
resistance strategies are not necessarily tightly coupled with resource-use
strategies. Overall, our study demonstrates the importance of considering
intraspecific variation in analyses of the vulnerability of tropical trees to
climate change.
PMID- 28419348
TI - Litchi Fruit LcNAC1 is a Target of LcMYC2 and Regulator of Fruit Senescence
Through its Interaction with LcWRKY1.
AB - Senescence is a key factor resulting in deterioration of non-climacteric fruit.
NAC transcription factors are important regulators in plant development and
abiotic stress responses, yet little information regarding the role of NACs in
regulating non-climacteric fruit senescence is available. In this study, we
cloned 13 NAC genes from litchi (Litchi chinensis) fruit, and analyzed
subcellular localization and expression profiles of these genes during post
harvest natural and low-temperature-delayed senescence. Of the 13 NAC genes,
expression of LcNAC1 was up-regulated in the pericarp and pulp as senescence
progressed, and was significantly higher in senescence-delayed fruit than that in
naturally senescent fruit. LcNAC1 was induced by exogenous ABA and hydrogen
peroxide. Yeast one-hybrid analysis and transient dual-luciferase reporter assay
showed that LcNAC1 was positively regulated by the LcMYC2 transcription factor.
LcNAC1 activated the expression of LcAOX1a, a gene associated with reactive
oxygen species regulation and energy metabolism, whereas LcWRKY1 repressed
LcAOX1a expression. In addition, LcNAC1 interacted with LcWRKY1 in vitro and in
vivo. These results indicated that LcNAC1 and LcWRKY1 form a complex to regulate
the expression of LcAOX1a antagonistically. Taken together, the results reveal a
hierarchical and co-ordinated regulatory network in senescence of harvested
litchi fruit.
PMID- 28419349
TI - Genomic Signature of Kin Selection in an Ant with Obligately Sterile Workers.
AB - Kin selection is thought to drive the evolution of cooperation and conflict, but
the specific genes and genome-wide patterns shaped by kin selection are unknown.
We identified thousands of genes associated with the sterile ant worker caste,
the archetype of an altruistic phenotype shaped by kin selection, and then used
population and comparative genomic approaches to study patterns of molecular
evolution at these genes. Consistent with population genetic theoretical
predictions, worker-upregulated genes experienced reduced selection compared with
genes upregulated in reproductive castes. Worker-upregulated genes included more
taxonomically restricted genes, indicating that the worker caste has recruited
more novel genes, yet these genes also experienced reduced selection. Our study
identifies a putative genomic signature of kin selection and helps to integrate
emerging sociogenomic data with longstanding social evolution theory.
PMID- 28419350
TI - Epidemiology of Meningitis and Encephalitis in the United States, 2011-2014.
AB - Background: Large epidemiological studies evaluating the etiologies, management
decisions, and outcomes of adults with meningitis or encephalitis in the United
States (US) are lacking. Methods: Adult patients (>=18 years) with meningitis or
encephalitis by International Classification of Diseases, Ninth Revision codes
available in the Premier Healthcare Database during 2011-2014 were analyzed.
Results: A total of 26429 patients with meningitis or encephalitis were
identified. The median age was 43 years; 53% were female. The most common
etiology was enterovirus (13463 [51.6%]), followed by unknown (4944 [21.4%]),
bacterial meningitis (3692 [14.1%]), herpes simplex virus (2184 [8.3%]),
noninfectious (921 [3.5%]), fungal (720 [2.7%]), arboviruses (291 [1.1%]), and
other viruses (214 [0.8%]). Empiric antibiotics, antivirals, and antifungals were
administered in 85.8%, 53.4%, and 7.8%, respectively, and varied by etiologies.
Adjunctive steroids were utilized in 15.9% of all patients and in 39.3% of
patients with pneumococcal meningitis, with an associated decrease in mortality
(6.67% vs 12.5%, P = .0245). The median length of stay was 4 days, with the
longest duration in those with fungal (13), arboviral (10), and bacterial
meningitis (7). Overall inpatient mortality was 2.9% and was higher in those with
bacterial (8.2%), fungal (8.2%), or arboviral (8.9%) disease. Overall readmission
rate at 30 days was 3.2%; patients with arboviral (12.7%), bacterial (6.7%), and
fungal (5.4%) etiologies had higher rates. Conclusions: Viruses are the most
common cause of meningitis and encephalitis in the United States and are treated
with antibiotic therapy in the majority of cases. Adjunctive steroid treatment is
underutilized in pneumococcal meningitis, where it has shown to decrease
mortality.
PMID- 28419351
TI - The effect of diatomaceous earth in live, attenuated infectious bronchitis
vaccine, immune responses, and protection against challenge.
AB - Live virus vaccines are commonly used in poultry production, particularly in
broilers. Massive application and generation of a protective local mucosal and
humoral immunity with no adverse effects is the main goal for this strategy. Live
virus vaccines can be improved by adding adjuvants to boost mucosal innate and
adaptive responses. In a previous study we showed that diatomaceous earth (DE)
can be used as adjuvant in inactivated vaccines. The aim of this study was to
test DE as adjuvant in an Ark-DPI live infectious bronchitis virus (IBV) vaccine
after ocular or spray application. Titrating the virus alone or after addition of
DE showed that DE had no detrimental effect on the vaccine virus. However, adding
DE to the vaccine did not induce higher IgG titers in the serum and IgA titers in
tears. It also did not affect the frequency of CD4+ T cells, CD8+ T cells and
monocytes/macrophages in the blood and the spleen determined by flow cytometry.
In addition, protection generated against IBV homologous challenges, measured by
viral load in tears, respiratory signs and histopathology in tracheas, did not
vary when DE was present in the vaccine formulation. Finally, we confirmed
through our observations that Ark vaccines administered by hatchery spray cabinet
elicit weaker immune responses and protection against an IBV homologous challenge
compared to the same vaccine delivered via ocular route.
PMID- 28419352
TI - Dermatophytes and dermatophytosis in the eastern and southern parts of Africa.
AB - Dermatophytosis is currently a disease of global importance and a public health
burden. It is caused by dermatophytes, which attack and grow on dead animal
keratin. Dermatophytes belong to three genera, namely, Epidermophyton,
Microsporum, and Trichophyton. The predominant clinical forms and causative
agents vary from one region of the world to another. Poor socioeconomic status,
high population densities, and poor sanitary conditions are some of the factors
responsible for the high prevalence of dermatophytosis in many developing
countries, which include countries in southern and eastern Africa, the focus of
this review. To the best of our knowledge, there is currently no review article
on published findings on dermatophytosis in the eastern and southern parts of
Africa. This information will be of interest to the medical and research
community since the world has become a global village. This review covers
published research findings in eastern and southern regions of Africa until this
date. The countries covered in the current review include Kenya, Ethiopia,
Tanzania, South Africa, Mozambique, Madagascar, Malawi, Rwanda, Burundi, Uganda,
Zambia, Zimbabwe, and Botswana. T. violaceum is the most common human etiological
agent in all the countries under review with prevalence ranging from 56.7% to
95%, except for Madagascar (M. langeronii, reclassified as M. audouinii), Uganda
(M. gypseum) and Malawi (M. audouinii). Tinea capitis was the most clinical type,
followed by tinea corporis. Etiological agents of animal dermatophytoses were
variable in the countries where they were reported. Major risk factors for
dermatophytoses are age, climatic, and socioeconomic factors.
PMID- 28419353
TI - The effect of Ramadan fast on the incidence of renal colic emergency department
visits.
AB - Background: Renal colic (RC) is one of the most common reasons for emergency
department (ED) visits. Although RC is associated with high ambient temperature
and with physiological changes that occur during fast, the literature on between
Ramadan and RC incidence is scarce. Aim: To investigate the association of ED
visits with RC during Ramadan fast. Methods: We obtained health data of patients
visited the ED of a large tertiary centre during the years 2004-15, with a
primary diagnosis of RC. To estimate the association of RC and Ramadan, we
utilized bi-weekly RC incidence Poisson models adjusted for ambient temperature
and seasonality in two ethnic groups residing in the region: Muslims and Jews.
Results: We identified 10 435 unique patients with 18 163 ED visits with primary
diagnosis of RC. Although Muslims represent 18.5% of the population in the
region, approximately 25% of the ED visits with RC attributed to this group.
There was a positive and significant association of temperature and ED visits
within all subgroups after adjusting for seasons. Positive association with
Ramadan was observed during the first 2 weeks of fast within Muslims (R.R 1.27,
95% C.I 1.03-1.50) but not within Jewish community (R.R 1.061, 95% C.I 0.855
1.238). Conclusion: Our study demonstrates a significant and positive association
between RC and Ramadan, while controlling to ambient temperature. In view of
these findings, different prevention strategies should be investigated.
PMID- 28419354
TI - Work organization, sleep and metabolic syndrome among long-haul truck drivers.
AB - Background: The work organization of long-haul truck drivers in the USA contains
factors that have been shown to degrade sleep. In combination, these factors
generate elevated cardiometabolic risk by inducing components of the metabolic
syndrome (MetS). However, the prevalence and severity of MetS and the degree to
which such factors differentially influence MetS among these drivers are unknown.
Aims: To determine the prevalence and severity of MetS among US long-haul truck
drivers and to determine the predictive value of demographic, work organization
and sleep variables in MetS diagnosis and severity. Methods: A non-experimental,
descriptive, cross-sectional study, designed to collect survey, anthropometric
and biometric data from US long-haul truck drivers. Descriptive analyses were
performed for demographic, work organization, sleep and MetS measures. Logistic
and linear regression analyses examined potential predictive relationships
between demographic, work organization and sleep variables and MetS diagnosis and
severity. Results: The study population was 262. Nearly 60% of drivers met MetS
diagnosis criteria. Over 80% had a waist circumference >102 cm, 50% had
triglyceride levels of >=150 mg/dl, 66% had an high-density lipoprotein of <40
mg/dl, 28% had a blood pressure of >=135/80 mm Hg and 17% had a fasting glucose
of >=110 mg/dl. Driving experience and work day sleep quality were associated
with MetS prevalence and severity. Conclusions: The prevalence and severity of
MetS among this sample of US long-haul truck drivers were high. Preventive
efforts should focus on experienced drivers and work day sleep quality.
PMID- 28419355
TI - Vegetable Garden as Therapeutic Horticulture for Patients with Chronic Pain.
PMID- 28419356
TI - Arousal-Induced Hypocapnia Does Not Reduce Genioglossus Activity in Obstructive
Sleep Apnea.
AB - Study Objectives: To determine whether arousals that terminate obstructive events
in obstructive sleep apnea (OSA) (1) induce hypocapnia and (2) subsequently
reduce genioglossus muscle activity following the return to sleep. Methods:
Thirty-one untreated patients with OSA slept instrumented with sleep staging
electrodes, nasal mask and pneumotachograph, end-tidal CO2 monitoring, and
intramuscular genioglossus electrodes. End-tidal CO2 was monitored, and
respiratory arousals were assigned an end-arousal CO2 change value (PETCO2 on the
last arousal breath minus each individual's wakefulness PETCO2). This change
value, in conjunction with the normal sleep related increase in PETCO2, was used
to determine whether arousals induced hypocapnia and whether the end-arousal CO2
change was associated with genioglossus muscle activity on the breaths following
the return to sleep. Results: Twenty-four participants provided 1137 usable
arousals. Mean +/- SD end-arousal CO2 change was -0.2 +/- 2.4 mm Hg (below
wakefulness) indicating hypocapnia typically developed during arousal. Following
the return to sleep, genioglossus muscle activity did not fall below prearousal
levels and was elevated for the first two breaths. End-arousal CO2 change and
genioglossus muscle activity were negatively associated such that a 1 mm Hg
decrease in end-arousal CO2 was associated with an ~2% increase in peak and tonic
genioglossus muscle activity on the breaths following the return to sleep.
Conclusions: Arousal-induced hypocapnia did not result in reduced dilator muscle
activity following return to sleep, and thus hypocapnia may not contribute to
further obstructions via this mechanism. Elevated dilator muscle activity
postarousal is likely driven by non-CO2-related stimuli.
PMID- 28419357
TI - Stereoelectroencephalography Using Magnetic Resonance Angiography for Avascular
Trajectory Planning: Technical Report.
AB - BACKGROUND: Stereoelectroencephalography (SEEG) requires high-quality
angiographic studies because avascular trajectory planning is a prerequisite for
the safety of this procedure. Some epilepsy surgery groups have begun to use
computed tomography angiography and magnetic resonance T1-weighted sequence with
contrast enhancement for this purpose. OBJECTIVE: To present the first series of
patients with avascular trajectory planning of SEEG based on magnetic resonance
angiography (MRA). METHODS: Thirty-six SEEG explorations for drug-resistant focal
epilepsy were performed from January 2013 to December 2015. A retrospective
analysis of this consecutive surgical series was then performed. Magnetic
resonance imaging included MRA with a modified contrast-enhanced magnetic
resonance venography (MRV) protocol with a short acquisition delay, which allowed
simultaneous arterial and venous visualization. Our criteria for satisfactory MRA
were the visualization of at least first-order branches of the angular artery,
paracentral and calcarine artery, and third-order tributaries of the superficial
Sylvian vein, vein of Labbe, and vein of Trolard. RESULTS: Thirty-four patients
underwent 36 SEEG explorations with 369 electrodes carrying 4321 contacts.
Contrast-enhanced MRA using the MRV protocol was judged satisfactory for SEEG
planning in all explorations. Postoperative complications were not observed in
our series of 36 SEEG explorations, which included 50 transopercular insular
trajectories. CONCLUSION: MRA using an MRV protocol may be applied for avascular
trajectory planning during SEEG procedures. This technique provides a
simultaneous visualization of cortical arteries and veins without the need for
additional radiation exposure or intra-arterial catheter placement.
PMID- 28419358
TI - Early Cranioplasty is Associated with Greater Neurological Improvement: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Cranioplasty after decompressive craniectomy is a common
neurosurgical procedure, yet the optimal timing of cranioplasty has not been well
established. OBJECTIVE: To investigate whether the timing of cranioplasty is
associated with differences in neurological outcome. METHODS: A systematic
literature review and meta-analysis was performed using MEDLINE, Scopus, and the
Cochrane databases for studies reporting timing and neurological assessment for
cranioplasty after decompressive craniectomy. Pre- and postcranioplasty
neurological assessments for cranioplasty performed within (early) and beyond
(late) 90 d were extracted. The standard mean difference (SMD) was used to
normalize all neurological measures. Available data were pooled to compare pre
cranioplasty, postcranioplasty, and change in neurological status between early
and late cranioplasty cohorts, and in the overall population. RESULTS: Eight
retrospective observational studies were included for a total of 528 patients.
Studies reported various outcome measures (eg, Barthel Index, Karnofsky
Performance Scale, Functional Independence Measure, Glasgow Coma Scale, and
Glasgow Outcome Score). Cranioplasty, regardless of timing, was associated with
significant neurological improvement (SMD .56, P = .01). Comparing early and late
cohorts, there was no difference in precranioplasty neurological baseline;
however, postcranioplasty neurological outcome was significantly improved in the
early cohort (SMD .58, P = .04) and showed greater magnitude of change (SMD 2.90,
P = .02). CONCLUSION: Cranioplasty may improve neurological function, and earlier
cranioplasty may enhance this effect. Future prospective studies evaluating long
term, comprehensive neurological outcomes will be required to establish the true
effect of cranioplasty on neurological outcome.
PMID- 28419359
TI - Improving the Value of Medical Care for Patients with Back Pain.
PMID- 28419361
TI - Effect of electrical stunning frequency and current waveform in poultry welfare
and meat quality.
AB - This study aimed to evaluate the effects of different stunning frequencies and
electrical current waveforms on chicken welfare and meat quality. Two-hundred
thirty-two Cobb broilers, 48 d of age and 2.76 +/- 0.47 live-weight, were
randomly assigned into 4 stunning treatments - 2 frequencies (300 Hz and 650 Hz)
and 2 current waveforms (direct current [DC] and alternating current [AC]).
Broilers were electrically stunned in a water bath in a commercial slaughterhouse
(70 V, 100 mA). The electronarcosis and stunning efficiency were confirmed by
assessment of visual parameters (absence of rhythmic breathing, ocular reflex,
and coordinated wing flapping) and blood parameters (lactate, glucose, creatine
kinase, sodium, and potassium), which were measured after bleeding. The incidence
of traumas and injuries was assessed after plucking. Meat quality analysis was
performed in Pectoralis major (PM), with determinations of pH, breast yield
(PMY), water holding capacity (WHC), water absorption capacity (WAC), thawing
loss (DL), cooking loss (CL), shear force (SF), and instrumental color (a*, b*,
L*, C*, and h). The interaction between waveform and frequency was significant (P
< 0.05) only for lactate, sodium, and lightness (L*). Lactate and sodium levels
decreased at 300 Hz-DC. Meat lightness increased at 300 Hz-DC. The individual
effect of frequency was significant for glucose, creatine kinase, potassium, WHC,
PMY, b*, C*, and h. Regarding waveform, AC decreased plasma glucose and DC
decreased creatine kinase and WAC. In general, stunning frequency exerts greater
influence than waveform on the welfare and meat quality parameters of broilers.
The use of frequency at 650 Hz proved to render animals efficiently unconscious
and to promote greater meat quality.
PMID- 28419360
TI - P4HA1 mutations cause a unique congenital disorder of connective tissue involving
tendon, bone, muscle and the eye.
AB - Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and
stabilization of the triple helical domain of collagens. P4HA1 encodes the
catalytic alpha(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report
human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of
connective tissue, manifesting as early-onset joint hypermobility, joint
contractures, muscle weakness and bone dysplasia as well as high myopia, with
evidence of clinical improvement of motor function over time in the surviving
patient. Similar to P4ha1 null mice, which die prenatally, the muscle tissue from
P1 and P2 was found to have reduced collagen IV immunoreactivity at the muscle
basement membrane. Patients were compound heterozygous for frameshift and splice
site mutations leading to reduced, but not absent, P4HA1 protein level and C-P4H
activity in dermal fibroblasts compared to age-matched control samples.
Differential scanning calorimetry revealed reduced thermal stability of collagen
in patient-derived dermal fibroblasts versus age-matched control samples.
Mutations affecting the family of C-P4Hs, and in particular C-P4H-I, should be
considered in patients presenting with congenital connective tissue/myopathy
overlap disorders with joint hypermobility, contractures, mild skeletal dysplasia
and high myopia.
PMID- 28419362
TI - Obesity as a Presentation of Munchausen Syndrome by Proxy.
AB - Objective: To describe a case of an obese child whose weight gain was related to
the Munchausen Syndrome by proxy (MSP). Methods: This is a case report including
information regarding the child's clinical history and the mother's behavior. The
common features of the syndrome are confronted with the description of the case,
seeking to demonstrate the similarities. Results: The description ratifies the
diagnosis based on the signs and symptoms presented by the child (<5 years old,
frequent contacts with health system, symptoms witnessed only by the mother,
confusing findings, not helped by treatments, emotionally distant father) and the
attitude of the mother (concerned, interested in procedures, comfortable in the
medical setting, higher medical knowledge, hostile when thwarted). Conclusion:
The case presented points to a new etiology, the MSP, to be considered within the
set of factors currently known to cause and maintain obesity in childhood.
PMID- 28419363
TI - Applying 'drought' to potted plants by maintaining suboptimal soil moisture
improves plant water relations.
AB - Pot-based phenotyping of drought response sometimes maintains suboptimal soil
water content by applying high-frequency deficit irrigation (HFDI). We examined
the effect of this treatment on water and abscisic acid (ABA) relations of two
species (Helianthus annuus and Populus nigra). Suboptimal soil water content was
maintained by frequent irrigation, and compared with the effects of withholding
water and with adequate irrigation. At the same average whole-pot soil moisture,
frequent irrigation resulted in larger soil water content gradients, lower root
and xylem ABA concentrations ([X-ABA]), along with higher transpiration rates or
stomatal conductance, compared with plants from which water was withheld. [X-ABA]
was not uniquely related to transpiration rate or stomatal conductance, as
frequently irrigated plants showed partial stomatal closure compared with well
watered controls, without differing in [X-ABA] and, in H. annuus, [ABA]leaf. In
two P. nigra genotypes differing in leaf area, the ratio between leaf area and
root weight in the upper soil layer influenced the soil water content of this
layer. Maintaining suboptimal soil water content alters water relations, which
might become dependent on root distribution and leaf area, which influences soil
water content gradients. Thus genotypic variation in 'drought tolerance' derived
from phenotyping platforms must be carefully interpreted.
PMID- 28419364
TI - Examination of cryptococcal glucuronoxylomannan antigen in bronchoalveolar lavage
fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients.
AB - We clarified the performance of a cryptococcal glucuronoxylomannan (GXM) antigen
test using bronchoalveolar lavage fluid (BALF) samples, in an HIV-negative
Japanese population. Between March 2008 and December 2014, we examined
cryptococcal GXM antigens in both serum and BALF specimens from 429 cases at
Nagasaki University hospital. The diagnoses, underlying diseases, chest computed
tomography findings, and cryptococcal GXM antigen test results were
retrospectively investigated. Twenty-three patients were confirmed to have
pulmonary cryptococcosis, another six were clinically diagnosed with
cryptococcosis because they were seropositive for the GXM antigen, and five
possible cryptococcosis cases had BALF samples that were positive for the GXM
antigen and serum samples that were negative. The test's sensitivities for
detecting cryptococcal GXM antigens in serum and BALF samples, for confirmed
cases, were 73.9% and 82.6%, respectively, and their respective specificities
were 98.5% and 97.8%. Three of the five putative patients with cryptococcosis
were treated with antifungal agents; the pulmonary lesions decreased in size in
all treated patients. Both the BALF and serum GXM antigen titers showed positive
correlations with the lesion sizes; however, the serum antigen titers showed a
higher correlation (r = 0.490, P = .0033) than did the BALF titres (r = 0.312, P
= .0724). The rate of GXM-positive BALF samples was higher than the rate for
serum samples, especially for patients with pulmonary lesion diameters <=25 mm.
Testing for the presence of the cryptococcal GXM antigen in BALF specimens might
contribute to the early diagnosis of pulmonary cryptococcosis.
PMID- 28419365
TI - Redefining health for the 21st century: investing in well-being-the proper
meaning of 'health-care'.
PMID- 28419366
TI - Effect of methionine supplementation in chicken feed on the quality and shelf
life of fresh poultry meat.
AB - The aim of this study was to investigate the influence of different methionine
sources and concentrations on the quality and spoilage process of broiler meat.
The trial was comprised of 7 treatment groups: one basal group (suboptimal in
Methionine+Cysteine; i.e., 0.89, 0.74, 0.69% in DM SID Met+Cys in starter,
grower, and finisher diets, respectively) and 3 doses (0.10, 0.25, and 0.40%) of
either DL-Methionine (DLM) or DL-2-hydroxy-4-methylthio butanoic acid (DL-HMTBA)
on an equimolar basis of the DLM-supplemented groups. The broilers were fed the
diets for 35 d, then slaughtered and processed. The filets were aerobically
packed and stored under temperature controlled conditions at 4 degrees C. Meat
quality investigations were comprised of microbial investigations (total viable
count and Pseudomonas spp.), pH and drip loss measurements of the filets. The
shelf life of the meat samples was determined based on sensory parameters. After
slaughtering, all supplemented meat samples showed a high quality, whereby no
differences between the 2 methionine sources could be detected for the microbial
load, pH, and drip loss. In comparison to the control group, the supplemented
samples showed a higher sensory quality, characterized by a fresh smell and fresh
red color. Methionine supplementation had a significant influence on meat quality
parameters during storage. The microbial load, pH and drip loss of the chicken
filets were positively correlated to the methionine concentration. Additionally,
the microbial load at the end of storage was positively correlated to pH and drip
loss values. Nevertheless, the microbial parameters were in a normal range and
the positive correlation to methionine concentration did not affect the sensory
shelf life. The mean sensory shelf life of the broiler filets varied between 7 to
9 d. During storage, no difference in the development of sensory parameters was
observed between the supplemented groups, while the spoilage process of the basal
group occurred slightly faster. In conclusion, methionine concentration, but not
methionine source, effected meat quality parameters in breast muscles of
broilers.
PMID- 28419367
TI - Evaluating the Impact of LTA4H Genotype and Immune Status on Survival From
Tuberculous Meningitis.
PMID- 28419368
TI - Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral
Inflammation and Survival From Tuberculous Meningitis.
AB - Background: Tuberculous meningitis (TBM) is the most devastating form of
tuberculosis, yet very little is known about the pathophysiology. We hypothesized
that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which
determines inflammatory eicosanoid expression, influences intracerebral
inflammation, and predicts survival from TBM. Methods: We characterized the
pretreatment clinical and intracerebral inflammatory phenotype and 9-month
survival of 764 adults with TBM. All were genotyped for single-nucleotide
polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal
fluid (CSF) leukocyte and cytokine concentrations. Results: LTA4H genotype
predicted survival of human immunodeficiency virus (HIV)-uninfected patients,
with TT-genotype patients significantly more likely to survive TBM than CC
genotype patients, according to Cox regression analysis (univariate P = .040 and
multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF
proinflammatory cytokine concentrations, with intermediate and lower
concentrations in those with CT and CC genotypes. Increased CSF cytokine
concentrations correlated with more-severe disease, but patients with low CSF
leukocytes and cytokine concentrations were more likely to die from TBM. HIV
infection independently predicted death due to TBM (hazard ratio, 3.94; 95%
confidence interval, 2.79-5.56) and was associated with globally increased CSF
cytokine concentrations, independent of LTA4H genotype. Conclusions: LTA4H
genotype and HIV infection influence pretreatment inflammatory phenotype and
survival from TBM. LTA4H genotype may predict adjunctive corticosteroid
responsiveness in HIV-uninfected individuals.
PMID- 28419369
TI - Laboratory x-ray micro-computed tomography: a user guideline for biological
samples.
AB - Laboratory x-ray micro-computed tomography (micro-CT) is a fast-growing method in
scientific research applications that allows for non-destructive imaging of
morphological structures. This paper provides an easily operated "how to" guide
for new potential users and describes the various steps required for successful
planning of research projects that involve micro-CT. Background information on
micro-CT is provided, followed by relevant setup, scanning, reconstructing, and
visualization methods and considerations. Throughout the guide, a Jackson's
chameleon specimen, which was scanned at different settings, is used as an
interactive example. The ultimate aim of this paper is make new users familiar
with the concepts and applications of micro-CT in an attempt to promote its use
in future scientific studies.
PMID- 28419370
TI - Distinguishing industrial meat from that of indigenous chickens with molecular
markers.
AB - The aim of investigation was to evaluate a traceability system to detect
industrial chicken meat among indigenous products, considering issues that could
affect assignment accuracy. The dataset included 2 Italian indigenous meat
breeds, namely Bionda Piemontese (2 ecotypes) and Bianca di Saluzzo, one broiler
line, and 3 layer lines. Assignment tests were performed using a standard panel
of 28 microsatellite loci. To evaluate effects of inbreeding and substructure on
assignment accuracy, a simulated dataset was prepared. Broilers and layers belong
to homogeneous populations and never enter the clusters of indigenous breeds.
Ambiguity or misallocation are expected between the Bionda ecotypes and between
the 2 indigenous breeds, but it is unlikely that niche products provided by
Bionda and Bianca will compete with one another. Non-random mating reduces
accuracy, but only populations having weak genetic differentiation are involved,
namely those that are less interesting to discriminate. The dataset can be used
as a reference population to distinguish commercial meat from indigenous meat
with great accuracy. Misallocations increase as number of loci decreases, but
only within or between the indigenous breeds. A subpanel of the most resolving 14
loci keeps sufficient informative content to provide accuracy and to correctly
allocate additional test samples within the reference population. This analytical
tool is economically sustainable as a method to detect fraud or mislabeling.
Adoption of a monitoring system should increase the value of typical products
because the additional burden of molecular analyses would improve commercial
grade and perception of quality.
PMID- 28419371
TI - Sleep: A Window Into Autonomic Control in Children Born Preterm and Growth
Restricted.
AB - Study Objectives: Preterm birth and fetal growth restriction (FGR) are both
associated with risk of hypertension in adulthood. Mechanisms leading to this
pathology are unclear. In children aged 5-12 years, who were born preterm and
FGR, we used sleep as a tool to assess autonomic control with assessment of
cardiovascular structure and function. Methods: Eighteen children born preterm
and FGR, 15 children born preterm with appropriate birth weights for gestational
age (AGA), and 20 AGA term-born children were studied. Children underwent
overnight polysomnography with the addition of continuous noninvasive blood
pressure (FinometerTM). Spectral measures of heart rate variability (HRV), blood
pressure variability (BPV), and baroreflex sensitivity were assessed and
overnight urinary catecholamine levels measured. Echocardiographic studies
(Vivid7, GE Healthcare) were performed and vascular compliance assessed (Miller
InstrumentsTM). Statistical comparisons were adjusted for age and body size.
Results: Compared to term children, preterm AGA children had increased high
frequency HRV (p < .05) and BPV (p < .05) during sleep, reflecting increased
parasympathetic activation and blood pressure changes related to respiration.
Preterm FGR children had smaller left ventricular lengths, ascending aorta, and
left ventricular outflow tract diameter (p < .05 for all) and vascular compliance
was positively correlated with gestational age (r2 = 0.93, p < .05). Conclusions:
FGR combined with preterm birth did not alter autonomic control but altered heart
structure in children. In contrast, preterm birth alone altered autonomic control
but had no change in heart structure. These changes in children born preterm and
FGR may contribute, in part, to increased risk of cardiovascular disease later in
life but by different mechanisms.
PMID- 28419372
TI - Nutrient and fiber utilization responses of supplemental xylanase in broiler
chickens fed wheat based diets are independent of the adaptation period to test
diets.
AB - The effects of adaptation (AD) to xylanase-supplemented diets on nutrient and
fiber utilization in 21-d-old broilers were investigated. Six treatments,
arranged in two levels of AD (starting at d 0 or d 14 of age) and three levels of
xylanase (0 or 2,500 or 5,000 xylanase units/kg feed) were used. All diets had
500 phytase U/kg and 0.3% TiO2 as indigestible marker. A total of 384 d old male
broiler (Ross 308) chicks were divided into two groups. The first group was
assigned on weight basis to 24 cages (8 chicks per cage) and randomly allocated
to the diets from d 0. Birds in the second group were reared on a commercial
starter diet in the same room for 13 d. On d 14, the birds were individually
weighed, assigned on weight basis to 24 cages (8 chicks per cage), and randomly
allocated to the diets. Birds had free access to experimental diets and water.
Excreta samples were collected from d 18 to 21. On d 21, all birds were
euthanized to access ileal digesta. There was no interaction (P > 0.05) between
AD and xylanase on the apparent ileal digestibility (AID) and apparent retention
(AR) of components. The main effect of AD was such that the birds exposed to
diets for 7 d (d 14 to 21) had higher (P < 0.01) AID of energy than those exposed
for 21 d (d 0 to 21). In contrast, birds exposed to diets for 21 d had higher (P
< 0.05) AMEn and AR of neutral detergent fiber. Xylanase improvements (P < 0.01)
in the AID of energy and AMEn were dose dependent and coincided with linear
improvements (P < 0.05) in the AID of nitrogen, fat, and starch. In conclusion,
xylanase improvements on retention of fiber and nutrients were independent of AD
(7 or 21 d) suggesting that the xylanase effects are not transitional. Greater
retention of fiber with longer AD is suggestive of possible microbial adaptation.
PMID- 28419373
TI - Trends in the Prevalence of Morbid Obesity among Children and Adolescents in
Shandong, China, 1995-2014.
AB - Background: Childhood obesity has increased dramatically during the past decades;
however, data on the prevalence of morbid obesity is limited. The present study
examined the prevalent trends in morbid obesity among children and adolescents
during the past 19 years (1995-2014) in Shandong, China. Methods: Data for this
study were obtained from five cross-sectional surveys (1995, 2000, 2005, 2010 and
2014) of schoolchildren in Shandong Province, China. A total of 41 500 students
aged 7-18 years were included in this study. Body mass index cutoffs recommended
by the International Obesity Task Force were used to define morbid obesity.
Results: The prevalence of morbid obesity was increasing continuously during the
past 19 years (1995-2014), from 0.25% for boys and 0.11% for girls in 1995 to
2.73% for boys and 1.29% for girls in 2014. Boys had higher prevalence of morbid
obesity than girls (p<0.01). Regional socioeconomic status (SES) inequalities in
morbid obesity were observed; children and adolescents from high SES district had
a rapid increase in the prevalence of morbid obesity than their counterparts from
moderate SES and low SES districts in the past 19 years. Conclusion: Although the
current prevalence of morbid obesity was at a relatively low level, a continuous
increasing trend was observed between 1995 and 2014. We should not relax our
vigilance, and policymakers and experts should pay more attention to the
monitoring and prevention of morbid obesity among children and adolescents in the
future decades.
PMID- 28419374
TI - Patient Radiation Doses in Therapeutic Endoscopic Retrograde
Cholangiopancreatography in Patras and the Key Role of the Operator.
AB - The patient radiation doses, in conjunction with the operator experience, in
therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures,
performed in our hospital, were obtained. Ninety-six patients participated in the
study and were divided into 3 groups, based on the operator experience. The
dosemetric indices, fluoroscopy time (FT), cumulative dose (Ka,r) and air kerma
area product (PKA), were collected. For the total and weight banding group the
third quartile values of the distribution of FT, Ka,r and PKA were 2.90 and 2.92
min, 6.89 and 6.93 mGy and 1.84 and 1.85 Gycm2, respectively, and were
comparative or significantly lower than the corresponding values previously
reported. Taking as a criterion the operator, the differences in the patient
radiation doses were statistically significant, with the highest dose recorded
for the operator of the lowest experience degree. The values obtained could
contribute in establishing local and national diagnostic reference levels and in
optimising ERCP procedure.
PMID- 28419376
TI - Latent TB infection and pulmonary TB disease among patients with diabetes
mellitus in Bandung, Indonesia.
AB - Background: Screening and treatment of latent TB infection (LTBI) and TB disease
could reduce diabetes mellitus (DM)-associated TB. We aimed to describe the
prevalence of LTBI and pulmonary TB among patients with DM in a TB-endemic
setting. Methods: Patients with DM attending a hospital and community centres in
Bandung, Indonesia, underwent LTBI screening using interferon gamma release assay
(IGRA). TB was investigated by sputum smear, culture and x-ray. TB contacts from
a parallel study were age- and sex-matched to patients with DM to compare LTBI
and TB disease prevalence. Results: Of 682 patients with DM screened, 651 (95.5%)
were eligible. Among 'TB disease-free' patients, LTBI prevalence was 38.9%
(206/530; 95% CI 34.7-43.2). Patients with DM were less likely to be IGRA
positive than TB contacts (38.6%, 54/140; 95% CI 30.5-46.6 vs 68.6%, 96/140; 95%
CI 60.9-72.3: p<0.001); but had a higher disease prevalence (4.9%, 8/164; 95% CI
1.6-8.2 vs 1.2%, 2/164; 95% CI -0.5 to 2.9: p=0.054). Patients with DM in crowded
households had increased risk of LTBI (AOR 1.71; 95% CI 1.19-2.45). Conclusions:
LTBI prevalence in patients with DM was lower than in household contacts, but
patients with DM were more likely to have TB disease. Further studies should
explore possible benefits of LTBI screening and preventive therapy in patients
with DM in TB-endemic settings.
PMID- 28419375
TI - Transcriptional Profiling of Cholinergic Neurons From Basal Forebrain Identifies
Changes in Expression of Genes Between Sleep and Wake.
AB - Study objective: To assess differences in gene expression in cholinergic basal
forebrain cells between sleeping and sleep-deprived mice sacrificed at the same
time of day. Methods: Tg(ChAT-eGFP)86Gsat mice expressing enhanced green
fluorescent protein (eGFP) under control of the choline acetyltransferase (Chat)
promoter were utilized to guide laser capture of cholinergic cells in basal
forebrain. Messenger RNA expression levels in these cells were profiled using
microarrays. Gene expression in eGFP(+) neurons was compared (1) to that in eGFP(
) neurons and to adjacent white matter, (2) between 7:00 am (lights on) and 7:00
pm (lights off), (3) between sleep-deprived and sleeping animals at 0, 3, 6, and
9 hours from lights on. Results: There was a marked enrichment of ChAT and other
markers of cholinergic neurons in eGFP(+) cells. Comparison of gene expression in
these eGFP(+) neurons between 7:00 am and 7:00 pm revealed expected differences
in the expression of clock genes (Arntl2, Per1, Per2, Dbp, Nr1d1) as well as
mGluR3. Comparison of expression between spontaneous sleep and sleep-deprived
groups sacrificed at the same time of day revealed a number of transcripts (n =
55) that had higher expression in sleep deprivation compared to sleep. Genes
upregulated in sleep deprivation predominantly were from the protein folding
pathway (25 transcripts, including chaperones). Among 42 transcripts upregulated
in sleep was the cold-inducible RNA-binding protein. Conclusions: Cholinergic
cell signatures were characterized. Whether the identified genes are changing as
a consequence of differences in behavioral state or as part of the molecular
regulatory mechanism remains to be determined.
PMID- 28419377
TI - Gene-Tree Reconciliation with MUL-Trees to Resolve Polyploidy Events.
AB - Polyploidy can have a huge impact on the evolution of species, and it is a common
occurrence, especially in plants. The two types of polyploids-autopolyploids and
allopolyploids-differ in the level of divergence between the genes that are
brought together in the new polyploid lineage. Because allopolyploids are formed
via hybridization, the homoeologous copies of genes within them are at least as
divergent as orthologs in the parental species that came together to form them.
This means that common methods for estimating the parental lineages of
allopolyploidy events are not accurate, and can lead to incorrect inferences
about the number of gene duplications and losses. Here, we have adapted an
algorithm for topology-based gene-tree reconciliation to work with multi-labeled
trees (MUL-trees). By definition, MUL-trees have some tips with identical labels,
which makes them a natural representation of the genomes of polyploids. Using
this new reconciliation algorithm we can: accurately place allopolyploidy events
on a phylogeny, identify the parental lineages that hybridized to form
allopolyploids, distinguish between allo-, auto-, and (in most cases) no
polyploidy, and correctly count the number of duplications and losses in a set of
gene trees. We validate our method using gene trees simulated with and without
polyploidy, and revisit the history of polyploidy in data from the clades
including both baker's yeast and bread wheat. Our re-analysis of the yeast data
confirms the allopolyploid origin and parental lineages previously identified for
this group. The method presented here should find wide use in the growing number
of genomes from species with a history of polyploidy. [Polyploidy;
reconciliation; whole-genome duplication.].
PMID- 28419378
TI - Arsenic-induced testicular toxicity in Gallus gallus: Expressions of inflammatory
cytokines and heat shock proteins.
AB - The aim of the study is to investigate the effects of sub-chronic poisoning with
arsenic on the testes of chickens treated. Seventy-two 1-day-old chickens were
randomly divided into 4 groups and provided food with different doses arsenic.
The histological changes were examined. The mRNA levels of inflammatory factors,
including transcription factor nuclear factor-kappaB (NF-kappaB), tumor necrosis
factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), cyclooxygenase
2 (COX-2), prostaglandin E synthase (PTGEs), and heat shock proteins (Hsps),
including Hsp70, Hsp90, Hsp60, Hsp40, and Hsp27 were assessed by quantitative
real-time PCR in the testes of chickens. The protein expressions of iNOS, Hsp60,
and Hsp70 were detected by western blot. Increased mRNA and protein levels of
inflammatory factors and Hsps with testicular damage showed that arsenic-induced
testicular toxicity includes inflammatory and heat shock response in chickens,
and that increased Hsps levels may play a protective role in inflammation damage
induced by arsenic on the testes of chickens.
PMID- 28419379
TI - Central Sensitization Is Modulated Following Trigger Point Anesthetization in
Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo
Controlled, Crossover Study.
AB - Objective: Central sensitization (CS) with low peripheral pain thresholds (PPTs)
is a common finding among patients with chronic pain after whiplash (CPWI). While
it has been proposed that myofascial myofascial trigger points (MTrPs) may act as
modulators of central sensitization, previously reported findings are conflicting
and inconclusive. The present study was designed to investigate immediate
responsiveness of CS to alterations in nociceptive input. Design: Controlled,
double-blind, cross-over. Subjects: Thirty-one patients with chronic pain
(trapezius myalgia) and CS after whiplash. Methods: Participants were referred by
randomization to group A for injection of a single peripheral pain generator
(MTrP or other discrete tender point) with local anesthetic or to group B for
sham injection and cross-over. Documentation of PPT (Algometer), maximum jaw
opening (caliper), and grip strength (Vigorimeter), as well as subjective overall
pain (visual analog scale [VAS]), was made before and after each intervention.
Results: Statistical analysis of data (Student's t test, analysis of variance)
confirmed that peripheral pain thresholds were significantly higher and maximum
jaw opening significantly greater after anesthetizing a focal pain generator in
the trapezius, but not after a sham injection. In contrast with the objective
variables, subjective generalized pain improved (VAS) after not only an injection
of local anesthetic, but also, and to a similar extent, after a sham injection.
Conclusions: CS, as expressed by lowered PPT, is a rapidly adjusting
physiological response to nociceptive stimuli in some patients with chronic pain
after whiplash. PPT are likely modulated by myofascial tender points in selected
patients with CS. With reference to the present findings, surgical ablation of
MTrPs is discussed as a potential treatment modality for CS.
PMID- 28419380
TI - beta-Carboxysome bioinformatics: identification and evolution of new bacterial
microcompartment protein gene classes and core locus constraints.
AB - Carboxysomes are bacterial microcompartments (BMCs) that enhance CO2 fixation in
all cyanobacteria. Structurally, carboxysome shell proteins are classified
according to the type of oligomer formed: hexameric (BMC-H), trimeric (BMC-T) and
pentameric (BMC-P) proteins. To understand the forces driving the evolution of
the carboxysome shell, we conducted a bioinformatic study of genes encoding beta
carboxysome shell proteins, taking advantage of the recent large increase in
sequenced cyanobacterial genomes. In addition to the four well-established BMC-H
(CcmK1-4) classes, our analysis reveals two new CcmK classes, which we name CcmK5
and CcmK6. CcmK5 is phylogenetically closest to CcmK3 and CcmK4, and the ccmK5
gene is found only in genomes lacking ccmK3 and ccmk4 genes. ccmK6 is found
predominantly in heterocyst-forming cyanobacteria. The gene encoding the BMC-T
homolog CcmO is associated with the main carboxysome locus (MCL) in only 60% of
all species. We find five evolutionary origins of separation of ccmO from the
MCL. Transcriptome analysis demonstrates that satellite ccmO genes, in contrast
to MCL-associated ccmO genes, are never co-regulated with other MCL genes. The
dispersal of carboxysome shell genes across the genome allows for distinct
regulation of their expression, perhaps in response to changes in environmental
conditions.
PMID- 28419382
TI - Assessing Flight Potential of the Invasive Asian Longhorned Beetle (Coleoptera:
Cerambycidae) With Computerized Flight Mills.
AB - The Asian longhorned beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera:
Cerambycidae: Lamiinae), is an invasive woodborer that poses a serious threat to
urban and natural landscapes. In North America, this beetle is a quarantine pest,
and populations are subject to eradication efforts that consist of the
identification, removal, and destruction of infested host material, and removal
or prophylactic treatment of high-risk host plant species. To enhance Asian
longhorned beetle eradication protocols in landscapes with extensive host
availability, we assessed the dispersal potential of male and female adults of
varying age, mating, and nutritional status using computerized flight mills. In
total, 162 individuals were tethered to computerized flight mills for a 24-h
trial period to collect information on total distance flown, flight times and
velocities, and number and duration of flight bouts. Adult Asian longhorned
beetles (in all treatments) flew an average of 2,272 m within a 24-h period, but
are capable of flying up to 13,667 m (8.5 miles). Nutrition and age had the
greatest impacts on flight, with Asian longhorned beetle adults >5 d of age that
had fed having greater overall flight performance than any other group. However,
mating status, sex, and body size (pre-flight weight and elytron length) had a
minimal effect on flight performance. This information will be useful for
refining quarantine zones surrounding areas of infestation, and for providing
greater specificity as to the risk the Asian longhorned beetle poses within
invaded regions.
PMID- 28419381
TI - Enhancing faba bean (Vicia faba L.) genome resources.
AB - Grain legume improvement is currently impeded by a lack of genomic resources. The
paucity of genome information for faba bean can be attributed to the intrinsic
difficulties of assembling/annotating its giant (~13 Gb) genome. In order to
address this challenge, RNA-sequencing analysis was performed on faba bean (cv.
Wizard) leaves. Read alignment to the faba bean reference transcriptome
identified 16 300 high quality unigenes. In addition, Illumina paired-end
sequencing was used to establish a baseline for genomic information assembly.
Genomic reads were assembled de novo into contigs with a size range of 50-5000
bp. Over 85% of sequences did not align to known genes, of which ~10% could be
aligned to known repetitive genetic elements. Over 26 000 of the reference
transcriptome unigenes could be aligned to DNA-sequencing (DNA-seq) reads with
high confidence. Moreover, this comparison identified 56 668 potential splice
points in all identified unigenes. Sequence length data were extended at 461
putative loci through alignment of DNA-seq contigs to full-length, publicly
available linkage marker sequences. Reads also yielded coverages of 3466* and
650* for the chloroplast and mitochondrial genomes, respectively. Inter- and
intraspecies organelle genome comparisons established core legume organelle gene
sets, and revealed polymorphic regions of faba bean organelle genomes.
PMID- 28419383
TI - Cell Death Biomarkers and Obstructive Sleep Apnea: Implications in the Acute
Coronary Syndrome.
AB - Study Objectives: Nucleosomes and cell-free double-stranded DNA (dsDNA) have been
suggested as promising biomarkers in cell death-related diseases, such as acute
coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA)
in patients with ACS is unclear. Our aim was to evaluate the relationship between
OSA, dsDNA, and nucleosomes and to assess their potential implication in the
development of ACS. Methods: Up to 549 patients were included in the study and
divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All
patients underwent a sleep study, and serum concentrations of dsDNA and
nucleosomes were measured. Results: Nucleosome and dsDNA levels were higher in
patients with OSA than in controls (nucleosomes: 1.47 +/- 0.88 arbitary units
[AU] vs. 1.00 +/- 0.33 AU; p < .001, dsDNA: 315.6 +/- 78.0 ng/mL vs. 282.6 +/-
55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients
with ACS than in non-ACS, independently of the presence of OSA. Conclusions: Both
nucleosomes and dsDNA are increased in patients with OSA and might be related
with the high cardiovascular risk seen in these patients. The extensive cell
lysis during a myocardial infarction seems to be the major contributor to the
high biomarker levels, and OSA does not seem to be implicated in such elevation
when this acute event occurs. Clinical trial registration: NCT01335087
(clinicaltrials.gov).
PMID- 28419384
TI - Risk Factors for Serious Prescription Opioid-Induced Respiratory Depression or
Overdose: Comparison of Commercially Insured and Veterans Health Affairs
Populations.
AB - Objective: To characterize the risk factors associated with overdose or serious
opioid-induced respiratory depression (OIRD) among medical users of prescription
opioids in a commercially insured population (CIP) and to compare risk factor
profiles between the CIP and Veterans Health Administration (VHA) population.
Subjects and Methods: Analysis of data from 18,365,497 patients in the IMS
PharMetrics Plus health plan claims database (CIP) who were dispensed a
prescription opioid in 2009 to 2013. Baseline factors associated with an event of
serious OIRD among 7,234 cases and 28,932 controls were identified using
multivariable logistic regression. The CIP risk factor profile was compared with
that from a corresponding logistic regression among 817 VHA cases and 8,170
controls in 2010 to 2012. Results: The strongest associations with serious OIRD
in CIP were diagnosed substance use disorder (odds ratio [OR] = 10.20, 95%
confidence interval [CI] = 9.06-11.40) and depression (OR = 3.12, 95% CI = 2.84
3.42). Other strongly associated factors included other mental health disorders;
impaired liver, renal, vascular, and pulmonary function; prescribed fentanyl,
methadone, and morphine; higher daily opioid doses; and concurrent psychoactive
medications. These risk factors, except depression, vascular disease, and
specific opioids, largely aligned with VHA despite CIP being substantially
younger, including more females and less chronic disease, and having greater
prescribing prevalence of higher daily opioid doses, specific opioids, and most
selected nonopioids. Conclusions: Risk factor profiles for serious OIRD among US
medical users of prescription opioids with private or public health insurance
were largely concordant despite substantial differences between the populations
in demographics, clinical conditions, health care delivery systems, and clinical
practices.
PMID- 28419385
TI - Development and Feasibility of a Group-Based Therapeutic Yoga Program for Women
with Chronic Pelvic Pain.
AB - Objective: To develop a group-based therapeutic yoga program for women with
chronic pelvic pain (CPP) and explore the effects of this program on pain
severity, sexual function, and well-being. Methods: A yoga therapy program for
CPP was developed by a multidisciplinary panel of clinicians, researchers, and
yoga consultants. Women reporting moderate to severe pelvic pain for at least six
months were recruited into a single-arm trial. Participants attended twice weekly
group classes focusing on Iyengar-based yoga techniques and were instructed to
practice yoga at home an hour a week for six weeks. Participants self-rated the
severity of their pelvic pain using daily logs. The impact of participants' pain
on everyday activities, emotional well-being, and sexual function was assessed
using an Impact of Pelvic Pain (IPP) questionnaire. Sexual function was further
assessed using the Sexual Health Outcomes in Women Questionnaire (SHOW-Q).
Results: Among the 16 participants (age range = 31-64 years), average ratings of
the severity of pain "at its worst," "at its best," and "on average" decreased by
29%, 32%, and 34%, respectively, from start to six weeks (P < 0.05 for all).
Women demonstrated improvements in scores on IPP subscales for daily activities
(1.8 +/- 0.7 to 0.9 +/- 0.7, P < 0.001), emotional well-being (1.7 +/- 0.9 to 0.9
+/- 0.7, P = 0.005), and sexual function (1.9 +/- 1.1 to 1.0 +/- 0.9, P = 0.04).
Scores on the SHOW-Q "pelvic problem interference" scale also improved over six
weeks (53 +/- 23 to 27 +/- 23, P = 0.002). Conclusions: Findings provide
preliminary evidence of the feasibility of teaching women with CPP to practice
yoga to self-manage pain and improve quality of life and sexual function.
PMID- 28419386
TI - Association between salinity and hospital admission for hypertension: an
ecological case-control study in the Mekong Delta Region in Vietnam.
AB - Background: Drinking water in the Mekong Delta Region (MDR) is highly vulnerable
to salinity intrusion and this problem is expected to increase with the projected
climate change and sea level rise. Despite this, research on health effects of
saline contaminated water is scarce in this region. This study examines the risk
of hospital admission for hypertension in salinity-affected areas of the MDR.
Methods: Cases and controls were obtained from national/provincial hospital
admission records for 2013. The cases were adult patients whom hypertension
(ICD10-code: I10-I15) was primary diagnosis for admission. Of the 13 provinces in
the MDR, we identified seven as 'salinity exposed' and the remaining as 'non
exposed' areas. A multi-level logistic regression model was used to examine the
association between salinity exposure and hypertension outcome. Results: Of the
total 573 650 hospital admissions, 22 382 (~3.9%) were hypertensive cases. The
multi-level logistic model combining both individual and ecological factors
showed a 9% increase in risk (95% CI: 3-14%) of hypertension admission among
individuals in exposed areas compared to those in non-exposed areas. Conclusion:
In order to develop and promote appropriate adaptation strategies, further
research is recommended to identify the salt exposure pathways and consumption
behaviours in the salinity exposed areas.
PMID- 28419387
TI - Effect of Continuous Positive Airway Pressure Treatment on Health-Related Quality
of Life and Sleepiness in High Cardiovascular Risk Individuals With Sleep Apnea:
Best Apnea Interventions for Research (BestAIR) Trial.
AB - Study Objectives: The long-term effect of continuous positive airway pressure
(CPAP) on health-related quality of life (HRQOL) in patients with high
cardiovascular disease risk and obstructive sleep apnea (OSA) without severe
sleepiness is uncertain. We aimed to determine the effect of CPAP treatment on
HRQOL in individuals with moderate or severe OSA and cardiovascular disease (CVD)
or multiple CVD risk factors without severe sleepiness. Methods: In this
randomized, controlled, parallel group study, 169 participants were assigned to
treatment with CPAP or the control group (conservative medical therapy [CMT] or
CMT with sham CPAP). Analyses were based on an intention-to-treat approach.
Linear mixed effect models were fitted to compare the changes in the Medical
Outcomes Study Short Form-36 (SF-36) and in subjective sleepiness (Epworth
Sleepiness Scale [ESS]) between groups from baseline to the average of 6- and 12
month measurements. Results: CPAP improved several domains of HRQOL including
bodily pain (treatment effect 9.7 [95% confidence interval, CI 3.9 to 15.4]; p =
.001), vitality (5.7 [95% CI 1.5 to 9.9]; p = .008), general health (8.2 [95% CI
3.7 to 12.7]; p < .001), physical functioning (5.5 [95% CI 1.1 to 10.0]; p =
.016), and the physical health summary score (3.3 [95% CI 1.4 to 5.3]; p = .001).
CPAP also resulted in less daytime sleepiness (mean change in ESS -1.0 point [95%
CI -2.0 to -0.0]; p = .040). Conclusions: In patients with moderate-severe OSA at
high risk of cardiovascular events and without severe sleepiness, CPAP improved
daytime sleepiness and multiple domains of HRQOL over 6 to 12 months of follow
up, with the largest improvement observed for bodily pain.
PMID- 28419388
TI - Daytime Sleepiness Increases With Age in Early Adolescence: A Sleep Restriction
Dose-Response Study.
AB - Study Objectives: Daytime sleepiness increases across adolescence. This increase
is commonly attributed to insufficient sleep durations resulting from
increasingly limited time in bed. We tested the effects of 3 sleep schedules on
daytime sleepiness and whether these effects changed with age in early
adolescence. Methods: In 77 children ranging in age from 9.9 to 14 years,
objective (multiple sleep latency test [MSLT]) and subjective (Karolinska
sleepiness scale [KSS]) sleepiness was measured following 4 consecutive nights of
either 7, 8.5, or 10 hours in bed. All participants completed all 3 sleep
schedules. The order in which they completed the schedules was not randomized but
was accounted for in all statistical analyses. Results: Time in bed restriction
decreased sleep duration and increased objective and subjective daytime
sleepiness. Although the sleep durations did not change with age, the likelihood
of falling asleep during the MSLT increased with age. Nevertheless, sleep
restriction produced a greater increase in MSLT-measured sleepiness in younger
participants. Subjective sleepiness measured with the KSS increased with shorter
sleep duration, but this effect did not change with age. Conclusions: Increasing
objective daytime sleepiness in early adolescence cannot simply be attributed to
reduced sleep due to restricted sleep schedules. We propose that some of the
increased daytime sleepiness of adolescents is a consequence of adolescent brain
reorganization driven by synaptic pruning which decreases the intensity of waking
brain activity.
PMID- 28419389
TI - Letter: Guidelines for the Management of Severe Traumatic Brain Injury, Fourth
Edition.
PMID- 28419390
TI - Adolescent Stress as a Driving Factor for Schizophrenia Development-A Basic
Science Perspective.
AB - Schizophrenia has been associated with heightened stress responsivity in
adolescence that precedes onset of psychosis. We now report that multiple
stressors during adolescence in normal rats leads to deficits in adults analogous
to that seen in schizophrenia patients. Moreover, impairment of stress control by
lesion of the prelimbic prefontal cortex in adolescence caused previously
subthreshold levels of stress to induce these deficit states when tested as
adults. Thus, predisposition to stress hyper-responsivity, or exposure to
substantial stressors, during adolescence can trigger a cascade of events that
result in a schizophrenia-like profile in adults. This data can provide crucial
information with respect to identifying markers for schizophrenia vulnerability
early in life and, by mitigating the impact of stressors, prevent the transition
to psychosis.
PMID- 28419391
TI - Letter to the Editor: Short-Term Outcomes of Aflibercept Therapy for Diabetic
Macular Edema in Patients With Incomplete Response to Ranibizumab and/or
Bevacizumab.
PMID- 28419392
TI - Erratum for "Eight Questions With Darius Moshfeghi".
PMID- 28419393
TI - Role of Disorganization of Retinal Inner Layers as an Optical Coherence
Tomography Biomarker in Diabetic and Uveitic Macular Edema.
PMID- 28419394
TI - Use of Corticosteroids in the Treatment of Patients With Diabetic Macular Edema
Who Have a Suboptimal Response to Anti-VEGF: Recommendations of an Expert Panel.
AB - BACKGROUND AND OBJECTIVE: Guidance on the use of corticosteroids in the treatment
of diabetic macular edema (DME) is lacking. This study aimed to develop a
clinically recommended treatment paradigm for DME with emphasis on the role of
corticosteroids. PATIENTS AND METHODS: An expert panel of nine retinal
specialists in the United States developed consensus recommendations for DME
treatment through a modified Delphi process. RESULTS: The panelists typically use
intravitreal injections of vascular endothelial growth factor (VEGF) antagonists
as first-line treatment of DME and switch patients with an inadequate response to
anti-VEGF therapy (failure of best-corrected visual acuity to improve to 20/40 or
better because of edema after three to six monthly injections, or a less-than-50%
reduction in excess macular thickness after three to four monthly injections) to
intravitreal corticosteroid treatment. CONCLUSION: Intravitreal corticosteroids
have a potentially useful role in the treatment of patients with DME who have an
inadequate response to intravitreal anti-VEGF therapy. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:291-301.].
PMID- 28419395
TI - Choriocapillaris Changes Imaged by OCT Angiography After Half-Dose Photodynamic
Therapy for Chronic Central Serous Chorioretinopathy.
AB - BACKGROUND AND OBJECTIVE: To evaluate the choriocapillaris using optical
coherence tomographic angiography (OCTA) after half-dose verteporfin photodynamic
therapy (hd-PDT) for chronic central serous chorioretinopathy (CSC). PATIENTS AND
METHODS: We studied six eyes (six patients) with chronic CSC treated by hd-PDT.
OCTA was performed before, 1 week after, and 1 month after hd-PDT. The area of
flow abnormality at the choriocapillaris level within the PDT spot after hd-PDT
was compared with that before hd-PDT. RESULTS: Serous retinal detachment was
diminished in all eyes, with three achieving complete resolution at 1 month. On
OCTA, all eyes showed irregular choriocapillaris flow before hd-PDT. The areas of
abnormal flow shrank progressively at 1 month after hd-PDT. CONCLUSION: On OCTA,
choriocapillaris flow tended to recover at 1 month after hd-PDT. OCTA may be
clinically useful for evaluating choriocapillaris and the therapeutic effects of
hd-PDT for chronic CSC. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:302
310.].
PMID- 28419396
TI - Correlation Between Mesopic Retinal Sensitivity and Optical Coherence Tomographic
Metrics of the Outer Retina in Patients With Non-Atrophic Dry Age-Related Macular
Degeneration.
AB - BACKGROUND AND OBJECTIVE: To determine the correlation between mesopic retinal
sensitivity and optical coherence tomographic metrics of the outer retina in
patients with intermediate age-related macular degeneration (AMD). PATIENTS AND
METHODS: Participants with nonatrophic dry AMD underwent mesopic MP-3
microperimetry (Nidek, Padova, Italy) and both Nidek and Cirrus (Carl Zeiss
Meditec, Dublin, CA) spectral-domain optical coherence tomography (SD-OCT). The
volume of the outer retinal layers was measured on the Nidek SD-OCT scans using
the automatic segmentation algorithm of Navis-EX software. In addition, drusen
area and volume within a 5-mm circle centered on the fovea were determined using
the Cirrus Advanced RPE Analysis Tool. The mean retinal sensitivity at 8 degrees
and 10 degrees of fixation (5-mm and 6-mm circles) was calculated for every eye.
The correlation between retinal sensitivity and patient age, outer retinal layer
volume, drusen area, and drusen volume was assessed. RESULTS: Thirty-seven eyes
from 25 patients with non-atrophic dry AMD were included in the study. The mean
age of the patients was 76 years +/- 9 years. The mean sensitivity across the
whole tested retinal area was 24.9 dB +/- 2.4 dB, with a sensitivity of 25.1 dB
+/- 2.4 dB within the central 5-mm circle. Drusen area within the central 5-mm
circle was 0.7 mm2 +/- 0.89 mm2 with a drusen volume of 0.03 mm3 +/- 0.04 mm3.
Retinal pigment epithelium and photoreceptor outer segment (RPE + OS) volume was
1.96 mm3 +/- 0.1 mm3, and outer nuclear layer (ONL) volume was 1.91 mm3 +/- 0.17
mm3. There was a significant correlation between RPE + OS volume and retinal
sensitivity, as well as between patients' age and retinal sensitivity. There was
no significant correlation between drusen area or volume and retinal sensitivity,
nor between ONL volume and retinal sensitivity. CONCLUSION: In eyes with
nonatrophic AMD, retinal sensitivity is correlated with the RPE + OS volume, but
not the ONL volume or the area or volume of drusen. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:312-318.].
PMID- 28419397
TI - Influence of Retinal Pathology on the Reliability of Macular Thickness
Measurement: A Comparison Between Optical Coherence Tomography Devices.
AB - BACKGROUND AND OBJECTIVE: To evaluate the repeatability, reliability, and
comparability of macular thickness measurements between three optical coherence
tomography (OCT) machines in healthy eyes, eyes with diabetic macular edema
(DME), and eyes with neovascular age-related macular degeneration (nAMD).
PATIENTS AND METHODS: Twenty-three eyes with DME, 26 eyes with nAMD, and 24
healthy eyes as controls were evaluated. Scans were performed using the swept
source Triton (Topcon, Tokyo, Japan), the spectral-domain Cirrus (Carl Zeiss
Meditec, Dublin, CA), and the Spectralis (Heidelberg Engineering, Heidelberg,
Germany) machines. Scans were evaluated for central macular thickness (CMT),
presence of segmentation and fixation imaging artifacts (IA), re-scan
reliability, and agreement between machines and groups. RESULTS: Mean CMT was
significantly different between all OCT machines in all groups (P < .01 for all
comparisons). Manually correcting IA did not alter these results. There was good
scan repeatability among healthy and DME eyes for each machine, but poor
repeatability among the nAMD group with the Spectralis (P = .038). IA were
significantly increased in the presence of pathology. CONCLUSIONS: There is poor
agreement of CMT measurement between OCT machines in healthy eyes and those with
DME and nAMD. DME and nAMD have a significant effect on the rate of IA in scans.
Care is required when interpreting measurements from different OCT devices in
clinical practice and research settings. [Ophthalmic Surg Lasers Imaging Retina.
2017;48:319-325.].
PMID- 28419398
TI - Pre-Existing RPE Atrophy and Defects in the External Limiting Membrane Predict
Early Poor Visual Response to Ranibizumab in Neovascular Age-Related Macular
Degeneration.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to identify the rate of
early visual acuity poor responders in patients with neovascular age-related
macular degeneration (AMD) after the first intravitreal injection of ranibizumab
(Lucentis; Genentech, South San Francisco, CA) and to determine potential
predictors for early response. PATIENTS AND METHODS: Patients with choroidal
neovascularization secondary to AMD were evaluated before and 1 month after their
first ranibizumab treatment. Early poor responders were defined as eyes gaining
less than five letters 1 month after the first injection. RESULTS: Following the
first ranibizumab injection, 58% of 84 patients gained five or more letters.
Beyond 42% poor responders, 31% displayed foveal retinal pigment epithelium (RPE)
atrophy and 89% a loss of the external limiting membrane (ELM) integrity at
baseline. However, the amount of intra- and subretinal fluid, pigment epithelial
detachment (PED), and subfoveal fibrosis showed a similar distribution between
gainers and poor responders. CONCLUSION: Early poor responders present with more
RPE atrophy, as well as a loss of the ELM integrity at baseline optical coherence
tomography. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:326-332.].
PMID- 28419399
TI - Low Fluence Photodynamic Therapy Versus Graded Subthreshold Transpupillary
Thermotherapy for Chronic Central Serous Chorioretinopathy: Results From a
Prospective Study.
AB - BACKGROUND AND OBJECTIVE: The authors compare low fluence photodynamic therapy
(PDT) against graded subthreshold transpupillary thermotherapy (TTT) for chronic
central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Forty-two eyes of
42 patients with chronic CSC were included in this prospective, nonrandomized,
interventional trial. All patients were offered PDT as an initial intervention.
If they declined PDT, TTT was offered. RESULTS: Twenty patients underwent PDT and
22 underwent TTT. The difference in best-corrected visual acuity between the TTT
and PDT groups at baseline and at 6 months after treatment was not significant (P
= .728). The mean foveal thickness decreased significantly in both groups (P =
.001). However, patients in the TTT group required more treatments (P = .013) and
longer time for resolution of the CSC (P = .013). CONCLUSIONS: Both PDT and TTT
may be equally effective in the treatment of chronic CSC. Graded subthreshold TTT
may be a cost-effective and safe alternative for PDT. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:334-338.].
PMID- 28419400
TI - A Nine-Year Follow-Up of Macular Complications in Retinitis Pigmentosa and
Diabetes Mellitus.
AB - The authors report a 9-year follow-up of macular complications in a 66-year-old
woman affected with retinitis pigmentosa (RP) and type 2 diabetes mellitus.
Rarely, clinical signs of diabetic retinopathy are presented in a patient with
retinal dystrophy. This patient developed a bilateral diabetic macular edema
(DME), which made its management complex due to the multiple pathogenic processes
involved. Despite the chronicity of the DME, visual acuity remained stable
without therapy. To the authors' knowledge, this is the first report of DME in RP
with such a long follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:340
344.].
PMID- 28419401
TI - Unilateral Pigmented Paravenous Retinochoroidal Atrophy Associated With Presumed
Ocular Tuberculosis.
AB - This report describes a case of unilateral pigmented paravenous retinochoroidal
atrophy (PPRCA) in a patient with low-grade unilateral intermediate uveitis. A 31
year-old woman, previously diagnosed with intermediate uveitis in the right eye
(OD) presented to the clinic. Best-corrected visual acuity was 20/20 OD. Fundus
examination, fluorescein angiography, autofluorescence, and optical coherence
tomography OD were in keeping with a phenotypic diagnosis of PPRCA.
Electrophysiology showed severe photoreceptor dysfunction of both the rod and the
cone systems OD. Systemic workup revealed QuantiFERON-gold positive. This is the
first report of unilateral PPRCA secondary to presumed ocular tuberculosis.
[Ophthalmic Surg Lasers Imaging Retina. 2017;48:345-349.].
PMID- 28419402
TI - Autologous Free Internal Limiting Membrane Flap for Optic Nerve Head Pit With
Maculopathy.
AB - Optic disc pits (ODPs) are associated with serous macular detachment (SMD), which
causes visual loss in 25% to 75% patients with ODPs. There are various modalities
of noninvasive and invasive treatment options; however, the best method of
treatment is to seal the optic disc to prevent further egress of fluid into the
subretinal space. The authors report a technique that involves sealing of ODPs
with autologous free flap of the internal limiting membrane (ILM). After trans
pars plana vitrectomy, the ILM was peeled and plugged into the ODP. This
procedure gave good anatomical and functional success. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:350-353.].
PMID- 28419403
TI - Adaptive Optics of Small Choroidal Melanoma.
AB - The authors report the use of an adaptive optics (AO) system in an asymptomatic
patient with small choroidal melanoma. A noninvasive, novel assessment that
detected potential photoreceptor abnormalities in the retina overlying the
choroidal lesion and adjacent retina is presented. These findings may help
current clinical evaluation to monitor structural damage to the outer retina and
possibly justify earlier intervention in borderline cases. Future research is
warranted to recognize full potential of this imaging modality. [Ophthalmic Surg
Lasers Imaging Retina. 2017;48:354-357.].
PMID- 28419404
TI - Use of Evicel Fibrin Sealant in Optic Disc Pit-Associated Macular Detachment.
AB - Optic disc pit is a rare congenital anomaly of the optic nerve. Retinal
detachment is a common complication with poor outcomes. Many surgical
alternatives have been described for the treatment of this condition, producing
variable results. Herein, the authors describe four cases of optic disc pit
associated macular detachment managed with pars plana vitrectomy, fluid-air
exchange, drainage of subretinal fluid through the optic disc pit, temporal
peripapillary laser, and application of Evicel fibrin sealant (human) (Ethicon,
Bridgewater, NJ) over the optic disc head. Case 1 showed stable visual acuity and
improvement of subretinal fluid. Cases 2 and 3 showed visual acuity and
subretinal fluid improvements. At the 1-week follow-up visit, Case 4 showed
almost total subretinal fluid absorption. The sealant invariably disappeared
between 1 and 2 weeks and was tolerated by all patients. This case series
suggests that Evicel fibrin sealant may be considered as an adjunctive option in
the surgical treatment of optic disc pit-associated maculopathy. [Ophthalmic Surg
Lasers Imaging Retina. 2017;48:358-363.].
PMID- 28419405
TI - Optical Coherence Tomography Angiography Features in Melanocytoma of the Optic
Nerve.
AB - Optic disc melanocytoma (ODM) is a pigmented tumor with malignant potential
characterized clinically as a dark brown to black lesion with feathery margins.
The authors report a case of ODM and describe the utility of optical coherence
tomography angiography (OCTA) in detecting superficial tumor vascularization.
This case report demonstrated the ability of OCTA to reveal the fine abnormal
retinal vasculature on the surface of the lesion, a characteristic of ODM, which
has been previously correlated with tumor growth. [Ophthalmic Surg Lasers Imaging
Retina. 2017;48:364-366.].
PMID- 28419406
TI - Routine oro/nasopharyngeal suction versus no suction at birth.
AB - BACKGROUND: Oro/nasopharyngeal suction is a method used to clear secretions from
the oropharynx and nasopharynx through the application of negative pressure via a
suction catheter or bulb syringe. Traditionally, airway oro/nasopharyngeal
suction at birth has been used routinely to remove fluid rapidly from the
oropharynx and nasopharynx in vigorous and non-vigorous infants at birth.
Concerns relating to the reported adverse effects of oro/nasopharyngeal
suctioning led to a practice review and routine oro/nasopharyngeal suctioning is
no longer recommended for vigorous infants. However, it is important to know
whether there is any clear benefit or harm for infants whose oro/nasopharyngeal
airway is suctioned compared to infants who are not suctioned. OBJECTIVES: To
evaluate the effect of routine oropharyngeal/nasopharyngeal suction compared to
no suction on mortality and morbidity in newly born infants. SEARCH METHODS: We
used the standard search strategy of the Cochrane Neonatal Review group to search
the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 3),
MEDLINE via PubMed (1966 to April 18, 2016), Embase (1980 to April 18, 2016), and
CINAHL (1982 to April 18, 2016). We also searched clinical trials databases,
conference proceedings, and the reference lists of retrieved articles for
randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA:
Randomised, quasi-randomised controlled trials and cluster randomised trials that
evaluated the effect of routine oropharyngeal/nasopharyngeal suction compared to
no suction on mortality and morbidity in newly born infants with and without
meconium-stained amniotic fluid. DATA COLLECTION AND ANALYSIS: The review authors
extracted from the reports of the clinical trials, data regarding clinical
outcomes including mortality, need for resuscitation, admission to neonatal
intensive care, five minute Apgar score, episodes of apnoea and length of
hospital stay. MAIN RESULTS: Eight randomised controlled trials met the inclusion
criteria and only included term infants (n = 4011). Five studies included infants
with no fetal distress and clear amniotic fluid, one large study included
vigorous infants with clear or meconium-stained amniotic fluid, and two large
studies included infants with thin or thick meconium-stained amniotic fluid.
Overall, there was no statistical difference between oro/nasopharyngeal suction
and no oro/nasopharyngeal suction for all reported outcomes: mortality (typical
RR 2.29, 95% CI 0.94 to 5.53; typical RD 0.01, 95% CI -0.00 to 0.01; I2 = 0%,
studies = 2, participants = 3023), need for resuscitation (typical RR 0.85, 95%
CI 0.69 to 1.06; typical RD -0.01, 95% CI -0.03 to 0.00; I2 = 0%, studies = 5,
participants = 3791), admission to NICU (typical RR 0.82, 95% CI 0.62 to 1.08;
typical RD -0.03, 95% CI -0.08 to 0.01; I2 = 27%, studies = 2, participants =
997) and Apgar scores at five minutes (MD -0.03, 95% CI -0.08 to 0.02; I2 not
estimated, studies = 3, participants = 330). AUTHORS' CONCLUSIONS: The currently
available evidence does not support or refute the benefits or harms of routine
oro/nasopharyngeal suction over no suction. Further high-quality studies are
required in preterm infants or term newborn infants with thick meconium amniotic
fluid. Studies should investigate long-term effects such as neurodevelopmental
outcomes.
PMID- 28419407
TI - University of Chicago phase II consortium trial of selumetinib (MEKi)
demonstrates low tolerability and efficacy in relapsed DLBCL.
PMID- 28419408
TI - Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk
myelodysplastic syndromes: a retrospective, multicentre study.
AB - Iron chelation is controversial in higher risk myelodysplastic syndromes (HR
MDS), outside the allogeneic transplant setting. We conducted a retrospective,
multicentre study in 51 patients with transfusion-dependent, intermediate-to-very
high risk MDS, according to the revised international prognostic scoring system,
treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients
(71%) received azacitidine concomitantly. DFX was given at a median dose of 1000
mg/day (range 375-2500 mg) for a median of 11 months (range 0.4-75). Eight
patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom
(8%) required drug interruption. Median ferritin levels decreased from 1709 MUg/l
at baseline to 1100 MUg/l after 12 months of treatment (P = 0.02). Seventeen
patients showed abnormal transaminase levels at baseline, which improved or
normalized under DFX treatment in eight cases. One patient showed a remarkable
haematological improvement. At a median follow up of 35.3 months, median overall
survival was 37.5 months. The results of this first survey of DFX in HR-MDS are
comparable, in terms of safety and efficacy, with those observed in lower-risk
MDS. Though larger, prospective studies are required to demonstrate real clinical
benefits, our data suggest that DFX is feasible and might be considered in a
selected cohort of HR-MDS patients.
PMID- 28419409
TI - Anti-Mullerian hormone exhibits a great variation in infertile women with
different ovarian reserve patterns.
AB - BACKGROUND: Several conflicting studies with results on the biological
variability of serum anti-Mullerian hormone (AMH) levels have been reported. Most
of the studies have not focused on whether the level of AMH fluctuations shows
variability by a baseline ovarian follicular reserve. AIM: To reveal whether
intracyclic variation in AMH levels occurs among women with adequate, high and
diminished ovarian reserve patterns. STUDY DESIGN: In this prospective cross
sectional study, 171 infertile women between the ages of 18 and 42 years were
recruited. All participants were divided into three types of ovarian reserve
patterns (adequate, high and diminished). Serum samples were tested for levels of
follicular AMH (F-AMH), luteal AMH (L-AMH), estradiol (E2), and follicle
stimulating hormone (FSH) and progesterone. RESULTS: The median age of the 171
participating women was 28 (18-42) years. The three ovarian reserve groups had
similar body mass index (BMI) and E2 (P = 0.797 and P = 0.135, respectively). The
serum AMH levels of all women and the three ovarian reserve groups in the
follicular phase were higher compared to those in the luteal phase (P < 0.001).
There were strong positive correlations between follicular and luteal AMH levels
in adequate, high and diminished reserve groups (Spearman r = 0.864, P < 0.001 vs
r = 0.899, P < 0.001 vs r = 0.863, P < 0.001, respectively). CONCLUSION: Serum
AMH levels were higher during the follicular phase than the luteal phase in women
with adequate, high and diminished ovarian patterns. Since the highest AMH levels
are demonstrated during the follicular phase, the optimal time to measure AMH
concentration might be during the follicular phase.
PMID- 28419411
TI - Pressure waveforms to assess epidural placement: is there a role on delivery
suite?
PMID- 28419410
TI - Selective and state-dependent activation of TRESK (K2P 18.1) background potassium
channel by cloxyquin.
AB - BACKGROUND AND PURPOSE: Cloxyquin (5-cloroquinolin-8-ol) has been described as an
activator of TRESK (K2P 18.1, TWIK-related spinal cord K+ channel) background
potassium channel. We have examined the specificity of the drug by testing
several K2P channels. We have investigated the mechanism of cloxyquin-mediated
TRESK activation, focusing on the differences between the physiologically
relevant regulatory states of the channel. EXPERIMENTAL APPROACH: Potassium
currents were measured by two-electrode voltage clamp in Xenopus oocytes and by
whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons. KEY RESULTS:
Cloxyquin (100 uM) activated mouse and human TRESK 4.4 +/- 0.3 (n = 28) and 3.9
+/- 0.3-fold (n = 8), respectively. The drug selectively targeted TRESK in the
K2P channel family and exerted state-dependent effects. TRESK was potently
activated by cloxyquin in the resting state. However, after robust activation of
the current by the calcium signal, evoked by stimulation of Gq-coupled receptors,
the compound did not influence mouse TRESK and only slightly affected the human
channel. The constitutively active mutant channels, mimicking the
dephosphorylated state (S276A) or containing altered channel pore (F156A and
F364A), were not further stimulated by cloxyquin. In a subpopulation of isolated
DRG neurons, cloxyquin substantially activated the background potassium current.
CONCLUSIONS AND IMPLICATIONS: Cloxyquin activates TRESK by a Ca2+ /calcineurin
independent mechanism. The drug is specific for TRESK within the K2P channel
family and useful for studying TRESK currents in native cells. The state
dependent pharmacological profile of this channel should be considered in the
development of therapeutics for migraine and other nociceptive disorders.
PMID- 28419412
TI - Eliminating malignant cells from cryopreserved ovarian tissue is possible in
leukaemia patients.
AB - Reimplantation of cryopreserved ovarian tissue (OT) can successfully restore
ovarian function in young cancer patients after gonadotoxic treatment. However,
for patients with leukaemia, there is a risk of malignant cell transmission. Our
objective was to evaluate minimal disseminated disease in OT from leukaemia
patients and test a follicle isolation technique to obtain disease-free follicle
suspensions. Cryopreserved OT from 12 leukaemia patients was thawed and analysed
by histology and long-term xenografting in immunosuppressed mice. In 10 patients,
follicles were isolated from OT, and polymerase chain reaction (PCR) was
performed on tissue, digested ovarian suspensions and isolated follicle
suspensions to investigate leukaemic cell presence. Mean patient age was 17.1
years. An average of 3.2 follicles were isolated per mm2 of cortex. Xenografting
of OT induced leukaemic masses in 2/12 mice. PCR identified leukaemic cell
presence in 66% of OT. Malignant cells were also detected in digested ovarian
suspensions. However, none of the follicle samples (>2300 follicles tested)
showed any malignant cell presence after washing. This study demonstrates that it
is possible to recover large numbers of viable follicles from cryopreserved OT of
leukaemia patients. All isolated and washed follicle suspensions tested negative
for leukaemic cells, giving leukaemia patients genuine hope of fertility
restoration.
PMID- 28419413
TI - Long-term outcomes, secondary malignancies and stem cell collection following
bendamustine in patients with previously treated non-Hodgkin lymphoma.
AB - Despite the long history of bendamustine as treatment for indolent non-Hodgkin
lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term
data from three clinical trials to characterize the toxicity and efficacy of
patients receiving bendamustine. Data were available for 149 subjects at 21
sites. The median age was 60 years at the start of bendamustine (range 39-84),
and patients had received a median of 3 prior therapies. The histologies included
grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small
lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell
lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n =
2) and not reported (n = 2). The median event-free survival was 14.1 months. Nine
of 12 attempted stem cell collections were successful. With a median follow-up of
8.9 years, 23 patients developed 25 cancers, including 8 patients with
myelodysplastic syndrome/acute myeloid leukaemia. These data provide important
information regarding the long-term toxicity of bendamustine in previously
treated patients. A small but meaningful number of patients achieved durable
remissions following bendamustine. These rigorously collected, patient-level,
long-term follow-up data provide reassurance that bendamustine or bendamustine
plus rituximab is associated with efficacy and safety for patients with relapsed
or refractory indolent non-Hodgkin lymphoma.
PMID- 28419414
TI - Association between aggressive care and bereaved families' evaluation of end-of
life care for veterans with non-small cell lung cancer who died in Veterans
Affairs facilities.
AB - BACKGROUND: To the authors' knowledge, little is known regarding the relationship
between patients' and families' satisfaction with aggressive end-of-life care.
Herein, the authors examined the associations between episodes of aggressive care
(ie, chemotherapy, mechanical ventilation, acute hospitalizations, and intensive
care unit admissions) within the last 30 days of life and families' evaluations
of end-of-life care among patients with non-small cell lung cancer (NSCLC).
METHODS: A total of 847 patients with NSCLC (34% of whom were aged <65 years) who
died in a nursing home or intensive care, acute care, or hospice/palliative care
(HPC) unit at 1 of 128 Veterans Affairs Medical Centers between 2010 and 2012
were examined. Data sources included Veterans Affairs administrative and clinical
data, Medicare claims, and the Bereaved Family Survey. The response rate for the
Bereaved Family Survey was 62%. RESULTS: Greater than 72% of veterans with
advanced lung cancer who died in an inpatient setting had at least 1 episode of
aggressive care and 31% received chemotherapy within the last 30 days of life.
For all units except for HPC, when patients experienced at least 1 episode of
aggressive care, bereaved families rated care lower compared with when patients
did not receive any aggressive care. For patients dying in an HPC unit, the
associations between overall ratings of care and >=2 inpatient admissions or any
episode of aggressive care were not found to be statistically significant. Rates
of aggressive care were not associated with age, and family ratings of care were
similar for younger and older patients. CONCLUSIONS: Aggressive care within the
last month of life is common among patients with NSCLC and is associated with
lower family evaluations of end-of-life care. Specialized care provided within an
HPC unit may mitigate the negative effects of aggressive care on these outcomes.
Cancer 2017;123:3186-94. (c) 2017 American Cancer Society.
PMID- 28419416
TI - The Seventh Year.
PMID- 28419415
TI - Allostery at opioid receptors: modulation with small molecule ligands.
AB - : Opioid receptors are 7-transmembrane domain receptors that couple to
heterotrimeric G proteins. The endogenous ligands for opioid receptors are
peptides which bind to the orthosteric site on the receptors. The MU-opioid
receptor is the target for opioid analgesics, while the delta-opioid receptor has
been suggested as a target for pain management, migraine and depression.
Similarly, kappa-opioid receptors are involved in pain and depression and
nociceptin receptors in pain and mood behaviours. However, exogenous orthosteric
ligands for opioid receptors cause a myriad of on-target side effects. Recently,
selective allosteric ligands for MU- and delta-opioid receptors have been
described. These compounds bind to a site on the receptor distinct from the
orthosteric site. Occupation of this allosteric site leads to modulation of
orthosteric ligand binding affinity and/or efficacy. Allosteric modulators may be
positive, negative or silent (neutral) (PAMs, NAMs or SAMs respectively). PAMs
may have in vivo activity by enhancing the activity of exogenous drugs or
endogenous opioid peptides. Enhancing endogenous opioid peptide activity
maintains the temporal and spatial distribution of these molecules but improves,
and potentially qualitatively changes, activity at their cognate receptors which
could limit side effects compared with traditional opioid drugs. In this review,
we describe the rationale and promise for the development of allosteric
modulators for opioid receptors, the discovery of selective allosteric
modulators, the identification of potential allosteric sites on opioid receptors
and the mode of action of the modulators. LINKED ARTICLES: This article is part
of a themed section on Emerging Areas of Opioid Pharmacology. To view the other
articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
PMID- 28419417
TI - Changes in the Relation Between Competence Beliefs and Achievement in Math Across
Elementary School Years.
AB - Math competence beliefs and achievement are important outcomes of school-based
learning. Previous studies yielded inconsistent results on whether skill
development, self-enhancement, or reciprocal effects account for the interplay
among them. A development-related change in the direction of their relation in
the early school years might explain the inconsistency. To test this, 542 German
elementary school students (M = 7.95 years, SD = 0.58) were repeatedly
investigated over 24 months from Grade 2 to Grade 4. Math competence beliefs
declined and had a growing influence on subsequent math grades. This suggests
changes in the dominant direction of the relation from a skill development to a
reciprocal effects model during elementary school. Findings are discussed with
regard to their theoretical and practical implications.
PMID- 28419418
TI - Does surgery for deep infiltrating bowel endometriosis improve fertility? A
systematic review.
AB - INTRODUCTION: Reduced fertility is a major concern in women with endometriosis.
The influence of surgery of deep infiltrating endometriosis (DIE) affecting the
bowel wall on fertility is controversial and the literature on this field is
heterogeneous. In this review we addressed whether surgery for bowel DIE improves
the spontaneous pregnancy rate, and the results of in vitro fertilization (IVF),
and the potential risk of such surgery. MATERIAL AND METHODS: We conducted a
literature search including the terms "deep", "deep infiltrating", "bowel",
rectovaginal", "endometriosis", "fertility", "infertility" and "IVF" in PubMed.
RESULTS: No randomized controlled studies were found. Other publications of
relevance included four retrospective and three prospective observational
studies. Moreover, one retrospective study compared results of IVF treatment with
or without previous surgery for bowel DIE. All studies reported detailed data on
surgical complications. The poor data quality precluded firm conclusions. The
results indicate, however, the possibility that surgery for bowel DIE may improve
the spontaneous pregnancy rate, and positive effects on IVF outcome cannot be
excluded. Such surgery will be associated with risk of major complications.
CONCLUSION: The lack of proper data precludes conclusions on the potential role
for bowel DIE surgery to improve the spontaneous pregnancy rate and results of
IVF treatment. Positive effects cannot be excluded, but the definite risk of
major complications must be taken into account.
PMID- 28419420
TI - Reliability of pressure waveform analysis to determine correct epidural needle
placement in labouring women.
AB - Pressure waveform analysis provides a reliable confirmatory adjunct to the loss
of-resistance technique to identify the epidural space during thoracic epidural
anaesthesia, but its role remains controversial in lumbar epidural analgesia
during labour. We performed an observational study in 100 labouring women of the
sensitivity and specificity of waveform analysis to determine the correct
location of the epidural needle. After obtaining loss-of-resistance, the
anaesthetist injected 5 ml saline through the epidural needle (accounting for the
volume already used in the loss-of-resistance). Sterile extension tubing,
connected to a pressure transducer, was attached to the needle. An investigator
determined the presence or absence of a pulsatile waveform, synchronised with the
heart rate, on a monitor screen that was not in the view of the anaesthetist or
the parturient. A bolus of 4 ml lidocaine 2% with adrenaline 5 MUg.ml-1 was
administered, and the epidural block was assessed after 15 min. Three women
displayed no sensory block at 15 min. The results showed: epidural block present,
epidural waveform present 93; epidural block absent, epidural waveform absent 2;
epidural block present, epidural waveform absent 4; epidural block absent,
epidural waveform present 1. Compared with the use of a local anaesthetic bolus
to ascertain the epidural space, the sensitivity, specificity, positive and
negative predictive values of waveform analysis were 95.9%, 66.7%, 98.9% and
33.3%, respectively. Epidural waveform analysis provides a simple adjunct to loss
of-resistance for confirming needle placement during performance of obstetric
epidurals, however, further studies are required before its routine
implementation in clinical practice.
PMID- 28419419
TI - The isoprenoid derivative N6 -benzyladenosine CM223 exerts antitumor effects in
glioma patient-derived primary cells through the mevalonate pathway.
AB - BACKGROUND AND PURPOSE: N6 -Isopentenyladenosine (i6A) is a modified nucleoside
exerting in vitro and in vivo antiproliferative effects. We previously
demonstrated that the actions of i6A correlate with the expression and activity
of farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the
mevalonate (MVA) pathway, which is aberrant in brain cancer. To develop new anti
glioma strategies, we tested related compounds exhibiting greater activity than
i6A. EXPERIMENTAL APPROACH: We designed and synthesized i6A derivatives
characterized by the introduction of diverse chemical moieties in the N6 position
of adenosine and tested for their efficacy in U87 cells and in primary glioma
cultures, derived from patients. NMR-based structural analysis, molecular docking
calculations and siRNA mediated knockdown were used to clarify the molecular
basis of their action, targeting FPPS protein. KEY RESULTS: CM223, the i6A
derivative including a benzyl moiety in N6 position of adenine, showed marked
activity in selectively targeting glioma cells, but not normal human astrocytes.
This was due to induction of intrinsic pathways of apoptosis and inhibition of
proliferation, along with blockade of FPPS-dependent protein prenylation, which
counteracted oncogenic signalling mediated by EGF receptors. CONCLUSION AND
IMPLICATIONS: The biological effects together with structural data on interaction
of CM223 with FPPS, provided additional evidence for the correlation of the
i6A/CM223 antitumor activity with FPPS modulation. Because the MVA pathway is an
important promising target, CM223 and its derivatives should be considered
interesting active molecules in antiglioma research.
PMID- 28419421
TI - Upregulation of CD72 expression on CD19+ CD27+ memory B cells by CD40L in primary
immune thrombocytopenia.
AB - CD72 is a co-receptor of B cells and regulates B cell activation. Although
aberrant expression of CD72 has been reported in primary immune thrombocytopenia
(ITP), it is uncertain whether this aberrant expression is restricted to specific
B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are
unknown. In this study, we found higher frequency of CD19+ B cells, CD19+ CD27+
memory B cells and lower frequency of CD19+ CD27- naive B cells in active ITP
patients compared with controls and patients in remission. CD72 expression on
CD19+ CD27+ cells was upregulated in active ITP patients and correlated with
platelet count and anti-platelet autoantibodies. In vitro, CD40L could
specifically induce CD72 upregulation on CD19+ CD27+ B cells. In combination with
CD40L, interleukin (IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72
expression on CD19+ CD27+ B cells, whereas IL21 reduced CD72 upregulation.
CD72mRNA expression after CD40L stimulation was increased in ITP patients and
controls. Significant increase of CD40L on CD4+ T cells was correlated with CD72
expression on CD19+ CD27+ B cells in ITP patients. In conclusion, upregulation of
CD72 expression on CD27+ memory B cells might take part in the pathogenesis of
ITP. Elevated CD40L on CD4+ cells combined with cytokines might contribute to the
upregulation of CD72 expression on CD27+ memory B cells.
PMID- 28419423
TI - Feeling run down: exercise-induced pancytopenia.
PMID- 28419422
TI - Early mortality and complications in hospitalized adult Californians with acute
myeloid leukaemia.
AB - Few studies have evaluated the impact of complications, sociodemographic and
clinical factors on early mortality (death <=60 days from diagnosis) in acute
myeloid leukaemia (AML) patients. Using data from the California Cancer Registry
linked to hospital discharge records from 1999 to 2012, we identified patients
aged >=15 years with AML who received inpatient treatment (N = 6359).
Multivariate logistic regression analyses were used to assess the association of
complications with early mortality, adjusting for sociodemographic factors,
comorbidities and hospital type. Early mortality decreased over time (25.3%, 1999
2000; 16.8%, 2011-2012) across all age groups, but was higher in older patients
(6.9%, 15-39, 11.4%, 40-54, 18.6% 55-65, and 35.8%, >65 years). Major bleeding
[Odds ratio (OR) 1.5, 95% confidence interval (CI) 1.3-1.9], liver failure (OR
1.9, 95% CI 1.1-3.1), renal failure (OR 2.4, 95% CI 2.0-2.9), respiratory failure
(OR 7.6, 95% CI 6.2-9.3) and cardiac arrest (OR 15.8, 95% CI 8.7-28.6) were
associated with early mortality. Higher early mortality was also associated with
single marital status, low neighbourhood socioeconomic status, lack of health
insurance and comorbidities. Treatment at National Cancer Institute-designated
cancer centres was associated with lower early mortality (OR 0.5, 95% CI 0.4
0.6). In conclusion, organ dysfunction, hospital type and sociodemographic
factors impact early mortality. Further studies should investigate how
differences in healthcare delivery affect early mortality.
PMID- 28419424
TI - Single centre experience of the management of superficial vein thrombosis with
prophylactic low-molecular-weight heparin.
PMID- 28419425
TI - How abnormal is binge eating? 18-Year time trends in population prevalence and
burden.
AB - OBJECTIVE: Although findings suggest that binge eating is becoming increasingly
normative, the 'clinical significance' of this behaviour at a population level
remains uncertain. We aimed to assess the time trends in binge-eating prevalence
and burden over 18 years. METHOD: Six cross-sectional face-to-face surveys of the
Australian adult population were conducted in 1998, 2005, 2008, 2009, 2014, and
2015 (Ntotal = 15 126). Data were collected on demographics, 3-month prevalence
of objective binge eating (OBE), health-related quality of life, days out of
role, and distress related to OBE. RESULTS: The prevalence of OBE increased six
fold from 1998 (2.7%) to 2015 (13.0%). Health-related quality of life associated
with OBE improved from 1998 to 2015, where it more closely approximated
population norms. Days out of role remained higher among participants who
reported OBE, although decreased over time. Half of participants who reported
weekly (56.6%) and twice-weekly (47.1%) OBE reported that they were not
distressed by this behaviour. However, the presence of distress related to OBE in
2015 was associated with greater health-related quality-of-life impairment.
CONCLUSION: As the prevalence of binge eating increases over time, associated
disability has been decreasing. Implications for the diagnosis of disorders
associated with binge eating are discussed.
PMID- 28419426
TI - Clinical characteristics, prognosis and treatment of myelofibrosis patients with
severe thrombocytopenia.
PMID- 28419427
TI - How I manage children with neutropenia.
AB - Neutropenia, usually defined as a blood neutrophil count <1.5 * 109 /l, is a
common medical problem for children and adults. There are many causes for
neutropenia, and at each stage in life the clinical pattern of causes and
consequences differs significantly. I recommend utilizing the age of the child
and clinical observations for the preliminary diagnosis and primary management.
In premature infants, neutropenia is quite common and contributes to the risk of
sepsis with necrotizing enterocolitis. At birth and for the first few months of
life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and
predisposes to the risk of severe bacterial infections. Thereafter when a child
is discovered to have neutropenia, often associated with relatively minor
symptoms, it is usually attributed to autoimmune disorder or viral infection. The
congenital neutropenia syndromes are usually recognized when there are recurrent
infections, the neutropenia is severe and there are congenital anomalies
suggesting a genetic disorder. This review focuses on the key clinical finding
and laboratory tests for diagnosis with commentaries on treatment, particularly
the use of granulocyte colony-stimulating factor to treat childhood neutropenia.
PMID- 28419428
TI - Platelets: much more than bricks in a breached wall.
AB - Platelets have various roles in vascular biology and homeostasis. They are the
first actor in primary haemostasis and play important roles in thrombosis
pathogenesis, but they are also part of innate immunity, which initiates and
accelerate many inflammatory conditions. In some contexts, their immune functions
are protective, while in others they contribute to adverse inflammatory outcomes.
Platelets express numerous receptors and contain hundreds of secretory molecules
that are crucial for platelet functional responses. The capacity of platelets to
produce and secrete cytokines, chemokines and related molecules, under the
control of specific intracellular pathways, is intimately related to their key
role in inflammation. They are also able to intervene in tissue regeneration and
repair because they produce pro-angiogenic mediators. Due to this characteristic
platelets are involved in cancer progression and spreading. In this review we
discuss the complex role of platelets, which bridges haemostasis, inflammation
and immune response both in physiological and pathological conditions.
PMID- 28419429
TI - Mutational landscape of B-cell post-transplant lymphoproliferative disorders.
AB - It is currently unclear whether post-transplant diffuse large B-cell lymphomas
(PT-DLBCL) display a similar genomic landscape as DLBCL in immunocompetent
patients (IC-DLBCL). We investigated 50 post-transplant lymphoproliferative
disorders (PTLDs) including 37 PT-DLBCL samples for somatic mutations frequently
observed in IC-DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion
Torrent platform and a customized panel of 68 genes was performed on genomic DNA.
Non-tumoural tissue was sequenced to exclude germline variants in cases where
available. A control cohort of 76 IC-DLBCL was available for comparative
analyses. In comparison to IC-DLBCLs, PT-DLBCL showed more frequent mutations of
TP53 (P = 0.004), and absence of ATM and B2M mutations (P = 0.004 and P = 0.016,
respectively). In comparison to IC-DLBCLs, Epstein-Barr virus (EBV)+ PT-DLBCL had
fewer mutated genes (P = 0.007) and particularly fewer mutations in nuclear
factor-kappaB pathway-related genes (P = 0.044). TP53 mutations were more
frequent in EBV- PT-DLBCL as compared to IC-DLBCL (P = 0.001). Germinal centre B
cell (GCB) subtype of PT-DLBCL had fewer mutations and mutated genes than GCB-IC
DLBCLs (P = 0.048 and 0.04 respectively). Polymorphic PTLD displayed fewer
mutations as compared to PT-DLBCL (P = 0.001). PT-DLBCL differs from IC-DLBCL
with respect to mutations in genes related to DNA damage control and immune
surveillance, and EBV association is likely to have a bearing on the mutational
pattern.
PMID- 28419430
TI - The Role of Family Characteristics for Students' Academic Outcomes: A Person
Centered Approach.
AB - Using data from 1,571 ninth-grade students (Mage = 14.62) from 82 academic track
schools in Germany and their predominantly Caucasian middle-class parents,
configurations of different family characteristics reported by parents were
investigated. Latent profile analyses considering academic involvement, family
interest, parents' self-concept, child's need for support, and parents' time and
energy identified average, indifferent, motivated and engaged, motivated and
disengaged, and involved families. Cross-sectional and longitudinal associations
with students' motivational (self-concept, effort, and interest) and achievement
outcomes (achievement test and grades) in math were analyzed. Students from
families classified as motivated and disengaged showed higher initial levels
motivation and achievement. Over 5 months, these students also showed an increase
in self-concept and higher achievement than students from other family types.
PMID- 28419431
TI - Moving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical
Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.
AB - Exposure-response analyses of venetoclax in combination with bortezomib and
dexamethasone in previously treated patients with multiple myeloma (MM) were
performed on a phase Ib venetoclax dose-ranging study. Logistic regression models
were utilized to determine relationships, identify subpopulations with different
responses, and optimize the venetoclax dosage that balanced both efficacy and
safety. Bortezomib refractory status and number of prior treatments were
identified to impact the efficacy response to venetoclax treatment. Higher
venetoclax exposures were estimated to increase the probability of achieving a
very good partial response (VGPR) or better through venetoclax doses of 1,200 mg.
However, the probability of neutropenia (grade >=3) was estimated to increase at
doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg
daily was selected to optimally balance the VGPR or better rates and neutropenia
rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to
bortezomib.
PMID- 28419432
TI - A Global Synthesis of Managing Groundwater Dependent Ecosystems Under Sustainable
Groundwater Policy.
AB - Groundwater is a vital water supply worldwide for people and nature. However,
species and ecosystems that depend on groundwater for some or all of their water
needs, known as groundwater dependent ecosystems (GDEs), are increasingly
becoming threatened worldwide due to growing human water demands. Over the past
two decades, the protection and management of GDEs have been incorporated into
several water management policy initiatives worldwide including jurisdictions
within Australia, the European Union, South Africa, and the United States. Among
these, Australia has implemented the most comprehensive framework to manage and
protect GDEs through its water policy initiatives. Using a science-based
approach, Australia has made good progress at reducing uncertainty when selecting
management thresholds for GDEs in their water management plans. This has been
achieved by incorporating appropriate metrics for GDEs into water monitoring
programs so that information gathered over time can inform management decisions.
This adaptive management approach is also accompanied by the application of the
"Precautionary Principle" in cases where insufficient information on GDEs exist.
Additionally, the integration of risk assessment into Australia's approach has
enabled water managers to prioritize the most valuable and vulnerable ecologic
assets necessary to manage GDEs under Australia's national sustainable water
management legislation. The purpose of this paper is to: (1) compare existing
global policy initiatives for the protection and management of GDEs; (2)
synthesize Australia's adaptive management approach of GDEs in their state water
plans; and (3) highlight opportunities and challenges of applying Australia's
approach for managing GDEs under other water management policies worldwide.
PMID- 28419433
TI - Plant-soil feedbacks in declining forests: implications for species coexistence.
AB - Plant-soil feedbacks (PSFs) play a relevant role as drivers of species abundance,
coexistence, and succession in plant communities. However, the potential
contribution of PSFs to community dynamics in changing forest ecosystems affected
by global change drivers is still largely unexplored. We measured the direction,
strength and nature (biological vs. chemical) of PSFs experienced by coexisting
tree species in two types of declining Quercus suber forests of southwestern
Spain (open woodland vs. closed forest) invaded by the exotic soil pathogen
Phytophthora cinnamomi. To test PSFs in a realistic community context, we focused
not only on individual PSFs (i.e., comparing the growth of a tree species on
conspecific vs. heterospecific soil) but also calculated net-pairwise PSFs by
comparing performance of coexisting tree species on their own and each other's
soils. We hypothesized that the decline and death of Q. suber would alter the
direction and strength of individual and net-pairwise PSFs due to the associated
changes in soil nutrients and microbial communities, with implications for
recruitment dynamics and species coexistence. In support of our hypothesis, we
found that the decline of Q. suber translated into substantial alterations of
individual and net-pairwise PSFs, which shifted from mostly neutral to
significantly positive or negative, depending on the forest type. In both cases
however the identified PSFs benefited other species more than Q. suber (i.e.,
heterospecific positive PSF in the open woodland, conspecific negative PSF in the
closed forest). Our results supported PSFs driven by changes in chemical soil
properties (mainly phosphorus) and arbuscular mycorrhizal fungi, but not in
pathogen abundance. Overall, our study suggests that PSFs might reinforce the
loss of dominance of Q. suber in declining forests invaded by P. cinnamomi by
promoting the relative performance of non-declining coexisting species. More
generally, our results indicate an increase in the strength of net PSFs as
natural forests become disturbed by global change drivers (e.g., invasive
species), suggesting an increasingly important role of PSFs in forest community
dynamics in the near future.
PMID- 28419434
TI - Estimating species richness in hyper-diverse large tree communities.
AB - Species richness estimation is one of the most widely used analyses carried out
by ecologists, and nonparametric estimators are probably the most used techniques
to carry out such estimations. We tested the assumptions and results of
nonparametric estimators and those of a logseries approach to species richness
estimation for simulated tropical forests and five data sets from the field. We
conclude that nonparametric estimators are not suitable to estimate species
richness in tropical forests, where sampling intensity is usually low and
richness is high, because the assumptions of the methods do not meet the sampling
strategy used in most studies. The logseries, while also requiring substantial
sampling, is much more effective in estimating species richness than commonly
used nonparametric estimators, and its assumptions better match the way field
data is being collected.
PMID- 28419435
TI - Osteogenic differentiation potential of mesenchymal stem cells cultured on
nanofibrous scaffold improved in the presence of pulsed electromagnetic field.
AB - Nowadays, tissue engineering by using stem cells in combination with scaffolds
and bioactive molecules has made significant contributions to the regeneration of
damaged bone tissues. Since the usage of bioactive molecules including, growth
factors to induce differentiation is safety limited in clinical applications, and
it has also been previously observed that extremely low frequency pulsed
electromagnetic fields (PEMF) can be effective in the enhancement of
proliferation rate and osteogenic differentiation of stem cells, the aim of this
study was investigating the osteoinductive potential of PEMF in combination with
Poly(caprolactone) (PCL) nanofibrous scaffold. To achieve this aim, Adipose
derived mesenchymal stem cells (ADSCs) isolated and characterized and then
osteogenic differentiation of them was investigated after culturing on the
surface of PCL scaffold under treatments of PEMF, PEMF plus osteogenic medium
(OM) and OM. Analysis of common osteogenic markers such as Alizarin red staining,
ALP activity, calcium content and four important bone-related genes in days of 7,
14, and 21 confirmed that the effects of PEMF on the osteogenic differentiation
of ADSCs are very similar to the effects of osteogenic medium. Thus, regarding
the immunological concerns about the application of bioactive molecules for
tissue engineering, PEMF could be a good alternative for osteogenic medium.
Although, results were showed a synergetic effect for simultaneous application of
PEMF and PCL scaffold in the osteogenesis process of ADSCs. Taking together,
ADSCs-seeded PCL nanofibrous scaffold in combination with PEMF could be a great
option for use in bone tissue engineering applications.
PMID- 28419436
TI - Ammonia oxidizer populations vary with nitrogen cycling across a tropical montane
mean annual temperature gradient.
AB - Functional gene approaches have been used to better understand the roles of
microbes in driving forest soil nitrogen (N) cycling rates and bioavailability.
Ammonia oxidation is a rate limiting step in nitrification, and is a key area for
understanding environmental constraints on N availability in forests. We studied
how increasing temperature affects the role of ammonia oxidizing archaea (AOA)
and bacteria (AOB) in soil N cycling and availability by using a highly
constrained natural mean annual temperature (MAT) elevation gradient in a
tropical montane wet forest. We found that net nitrate (NO3- ) bioavailability is
positively related to MAT (r2 = 0.79, P = 0.0033), and AOA DNA abundance is
positively related to both NO3- availability (r2 = 0.34, P = 0.0071) and MAT (r2
= 0.34, P < 0.001). In contrast, AOB DNA was only detected in some soils across
the gradient. We identified three distinct phylotypes within the AOA which
differed from one another in abundance and relative gene expression. In addition,
one AOA phylotype increased in abundance with MAT, while others did not. We
conclude that MAT is the primary driver of ecosystem N availability across this
gradient, and AOA population size and structure appear to mediate the
relationship between the nitrification and N bioavailability. These findings hold
important implications for nutrient limitation in forests and feedbacks to
primary production under changing climate.
PMID- 28419437
TI - A New Paradigm. "Learn - Learn More"; Dose-Exposure-Response at the Center of
Drug Development and Regulatory Approval.
AB - In his seminal paper, Lewis Sheiner introduced the "Learning versus Confirming"
paradigm. From that foundation, this work proposes why the precise estimation of
the dose-exposure-response (D-E-R) for both efficacy and safety endpoints should
be the ultimate goal for most drug development programs. The subsequent
identification and approval of an optimal dose regimen range will provide a
pragmatic framework for delivering personalized medicine based on dose titration
for each and every patient.
PMID- 28419438
TI - Dinosaur Tail Sign: A Useful Spinal MRI Finding Indicative of Cerebrospinal Fluid
Leakage.
AB - OBJECTIVE: To evaluate the imaging characteristics and diagnostic utility of the
"Dinosaur tail sign" in the diagnosis of cerebrospinal fluid (CSF) leakage.
BACKGROUND: The authors propose the "Dinosaur tail sign," defined as a
combination of the dorsal epidural hyperintensities, fat tissue, spinal cord, and
cauda equine on lumbosacral sagittal fat-suppressed T2-weighted image (FST2WI),
as a sensitive indicator for diagnosing CSF leakage. METHODS: Imaging
characteristics of the "Dinosaur tail sign" was evaluated in seven spontaneous
intracranial hypotension (SIH) and 23 iatrogenic CSF leakage (ICSFL) patients.
Additionally, the diagnostic index was compared between the "Dinosaur tail sign"
and other previously reported useful magnetic resonance imaging (MRI) and
magnetic resonance myelography (MRM) findings. RESULTS: In contrast to other
imaging findings including the epidural expansion, floating dural sac sign, and
distension of the spinal epidural veins on MRI, and paraspinal fluid collections
(PFC) on MRM, the "Dinosaur tail sign" was found equally in both SIH and ICSFL
patients (6 SIH and 19 ICSFL; 83% of all patients with CSF leakage). The
"Dinosaur tail sign" showed sufficient diagnostic utility (sensitivity 83%,
specificity 94%, accuracy 89%) that was comparable to that of PFC. CONCLUSION:
The "Dinosaur tail sign" is a useful imaging finding suggestive of CSF leakage.
Evaluation of subtle interspinous arched hyperintensities on spinal MRI is
mandatory for the diagnosis of SIH and ICSFL.
PMID- 28419439
TI - Effects of student pairing and public review on physical activity during school
recess.
AB - The purpose of this study was to evaluate the effects of student pairing and
feedback during recess on children's step counts. During baseline, participants
wore a sealed pedometer during recess. During intervention, we paired
participants with higher step counts with participants with lower step counts. We
encouraged teams to compete for the highest step count each day and provided
feedback on their performance during each recess session. Results showed a large
mean increase in step count from baseline to intervention. These results suggest
that children's steps during recess can be increased with a simple and cost
effective intervention.
PMID- 28419440
TI - The role of stromal cells in inflammatory bone loss.
AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
inflammation, local and systemic bone loss and a lack of compensatory bone
repair. Fibroblast-like synoviocytes (FLS) are the most abundant cells of the
stroma and a key population in autoimmune diseases such as RA. An increasing body
of evidence suggests that these cells play not only an important role in chronic
inflammation and synovial hyperplasia, but also impact bone remodelling. Under
inflammatory conditions FLS release inflammatory cytokines, regulate bone
destruction and formation and communicate with immune cells to control bone
homeostasis. Other stromal cells, such as osteoblasts and terminally
differentiated osteoblasts, termed osteocytes, are also involved in the
regulation of bone homeostasis and are dysregulated during inflammation. This
review highlights our current understanding of how stromal cells influence the
balance between bone formation and bone destruction. Increasing our understanding
of these processes is critical to enable the development of novel therapeutic
strategies with which to treat bone loss in RA.
PMID- 28419441
TI - Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of
acute lymphoblastic leukaemia patients: implications for minimal residual disease
detection.
AB - Flow cytometric detection of minimal residual disease (MRD) in children with B
cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic
discrimination between residual leukaemic cells and B-cell precursors (BCPs)
which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour
flow cytometry and innovative analysis tools were used to first characterize the
immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy
children, resulting in a continuous multiparametric pathway including transition
stages. This pathway was subsequently used as a reference to characterize the
immunophenotypic maturation of regenerating BCPs in BM from children treated for
BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in
contrast to the classical CD34high pre-B-I cell immunophenotype. These CD34-dim
pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I
subset), while hardly present in healthy control BM (9-13% within pre-B-I subset;
P = 0.0037). Furthermore, we showed that some of the BCP-ALL diagnosis
immunophenotypes (23%) overlapped with CD34-dim pre-B-I cells. Our results
indicate that newly identified CD34-dim pre-B-I cells can be mistaken for
residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes.
Therefore, regenerating BM, in which CD34-dim pre-B-I cells are relatively
abundant, should be used as reference frame in flow cytometric MRD measurements.
PMID- 28419442
TI - Characterization of Runx2 phosphorylation sites required for TGF-beta1-mediated
stimulation of matrix metalloproteinase-13 expression in osteoblastic cells.
AB - Transforming growth factor-beta1 (TGF-beta1), a highly abundant growth factor in
skeletal tissues, stimulates matrix metalloproteinase-13 (MMP-13) expression in
osteoblastic cells. MMP-13 plays a critical role in bone remodeling. Runx2, a
bone transcription factor, is required for TGF-beta1-mediated stimulation of MMP
13 expression in osteoblastic cells. In this study, the molecular mechanism
responsible for TGF-beta1-stimulation of MMP-13 expression via Runx2 in
osteoblastic cells was elucidated. TGF-beta1 stimulated the phosphorylation of
Runx2 at serine amino acids, and ERK inhibition blocked this effect in rat
(UMR106-01) and human (MG-63) osteoblastic cells. Pretreatment with okadaic acid,
a serine-threonine phosphatase inhibitor, increased Runx2 serine phosphorylation
in osteoblastic cells. When cells were pretreated with an ERK inhibitor, TGF
beta1-mediated stimulation of MMP-13 mRNA expression decreased. Nano-ESI/LC/MS
analysis identified that TGF-beta1 stimulates Runx2 phosphorylation at three
serine amino acids. Transient transfection of mouse mesenchymal stem cells
(C3H10T1/2) with Runx2 serine mutant constructs decreased TGF-beta1-mediated
Runx2 serine phosphorylation. A luciferase reporter assay identified that TGF
beta1 stimulated MMP-13 promoter activity in these cells only in the presence of
the wild Runx2 construct, and not with mutant Runx2. Thus, TGF-beta1 stimulates
the phosphorylation of Runx2 at three serine amino acids, and this event is
required for MMP-13 expression in osteoblastic cells. Hence, this study
contributes to the knowledge of events governing bone remodeling and bone-related
diseases.
PMID- 28419444
TI - A Self-Determination Theory Perspective on Postpartum Depressive Symptoms and
Early Parenting Behaviors.
AB - OBJECTIVE: On the basis of self-determination theory, this study investigates
longitudinal associations between satisfaction and frustration mothers' basic
psychological needs (i.e., autonomy, relatedness, competence) and mothers'
postnatal depressive symptoms and early parenting behaviors. METHOD: Participants
were 214 women assessed during their pregnancy (Time 1), 4 months after delivery
(Time 2), and when the child was 2 years old (Time 3). RESULTS: Results
demonstrate effects of prenatal basic psychological needs (needs frustration more
specifically) on postnatal depressive symptoms. In addition, general prenatal
needs satisfaction and frustration predicted more relationship-specific needs
satisfaction and frustration, respectively (in the mother-child relationship). In
turn, postnatal relationship-specific needs satisfaction predicted more high
quality parenting when the child is 2 years old. More specifically, needs
satisfaction was related to more maternal responsiveness and autonomy support.
CONCLUSION: Overall, these findings underscore the importance of psychological
needs experiences for both mothers' personal adjustment after birth and for the
early mother-child relationship.
PMID- 28419443
TI - Loss of natural killer T cells promotes pancreatic cancer in LSL-KrasG12D/+ mice.
AB - The role of the unique T-cell population, natural killer T (NKT) cells, which
have similar functions to NK cells in pancreatic cancer (PC), is not yet
evaluated. To address the regulatory roles of NKT cells on tumour progression
through tumour-associated macrophages (TAM) and their production of microsomal
prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven
pancreatic tumour (KPT) progression, we crossed CD1d-/- mice deficient in both
invariant and variant NKT cells with the KrasG12D mice. Loss of NKT cells
significantly increased pancreatic intraepithelial neoplasia (PanIN) lesions and
also increased 5-LOX and mPGES-1 expression in M2-type macrophages and cancer
stem-like cells in pancreatic tumours. Pharmacological inhibition of mPGES-1 and
5-LOX in M2 macrophages with specific inhibitor YS-121 in KPT-CD1d-/- mice
decreased PanIN lesions and suppressed tumour growth in association with elevated
levels of active CD8a cells. Hence, NKT cells regulate PC by modulating TAMs (M2)
through mPGES-1 and 5-LOX; and the absence of NKT cells leads to aggressive
development of PC.
PMID- 28419446
TI - From Autonomy to Divinity: The Cultural Socialization of Moral Reasoning in an
Evangelical Christian Community.
AB - This study examined moral reasoning in parent-child conversations within a U.S.
evangelical Christian community. The goal was to identify social-communicative
processes that may promote the development of Divinity in children's moral
reasoning. Sixteen parent-child dyads (6-9 years old) discussed hypothetical
moral vignettes about failures to help peers in need. Analyses revealed that
Divinity typically co-occurred with Autonomy in these conversations and that such
co-occurrences typically happened through three distinct social-communicative
processes, labeled "align," "scaffold," and "counter." Findings are used to
explain the shifting priority of Autonomy and Divinity over the life course among
members of evangelical Christian faiths that previous research has documented.
More broadly, findings highlight socialization processes through which children
can rationalize their developing moral outlooks in culturally distinct ways.
PMID- 28419445
TI - Activation of ClC-3 chloride channel by 17beta-estradiol relies on the estrogen
receptor alpha expression in breast cancer.
AB - Although extensively studied, the mechanisms by which estrogen promotes breast
cancer growth remain to be fully elucidated. Tamoxifen, an antiestrogen agent to
treat ERalpha+ breast cancer, is also a high-affinity blocker of the chloride
channels. In this study, we explored the involvement of the chloride channels in
the action of estrogen in breast cancer. We found that 17beta-estradiol (17beta
E2) concentration-dependently activated the chloride currents in ERalpha+ breast
cancer MCF-7 cells. Extracellular hypertonic challenge and chloride channel
blockers, NPPB and DIDS inhibited the 17beta-E2-activated chloride currents.
Decreased the ClC-3 protein expression caused the depletion of the 17beta-E2
activated chloride currents. 17beta-E2-activated chloride currents which relied
on the ERalpha expression were demonstrated by the following evidences. Firstly,
17beta-E2-activated chloride currents could not be observed in ERalpha- breast
cancer MDA-MB-231 cells. Secondly, ER antagonists, tamoxifen and ICI 182,780, and
downregulation of ERalpha expression inhibited or abolished the 17beta-E2
activated chloride currents. Thirdly, ERalpha expression was induced in MDA-MB
231 cells by ESR1 gene transfection, and then 17beta-E2-activated chloride
currents could be observed. In MCF-7 cells, ERalpha and ClC-3 mainly located in
nucleus and translocated to cell plasma and membrane with respect to co
localization following treatment of 17beta-E2. Downregulation of ERalpha
expression could decrease the expression of ClC-3 protein. Conversely,
downregulation of ClC-3 expression did not influence the ERalpha expression.
Taken together, our findings demonstrated that ClC-3 is a potential target of
17beta-E2 and is modulated by the ERalpha in breast cancer cell. Pharmacological
modulation of ClC-3 may provide a deep understanding in antiestrogen treatment of
breast cancer patients.
PMID- 28419447
TI - Divergence and evolution of assortative mating in a polygenic trait model of
speciation with gene flow.
AB - Assortative mating is an important driver of speciation in populations with gene
flow and is predicted to evolve under certain conditions in few-locus models.
However, the evolution of assortment is less understood for mating based on
quantitative traits, which are often characterized by high genetic variability
and extensive linkage disequilibrium between trait loci. We explore this scenario
for a two-deme model with migration, by considering a single polygenic trait
subject to divergent viability selection across demes, as well as assortative
mating and sexual selection within demes, and investigate how trait divergence is
shaped by various evolutionary forces. Our analysis reveals the existence of
sharp thresholds of assortment strength, at which divergence increases
dramatically. We also study the evolution of assortment via invasion of modifiers
of mate discrimination and show that the ES assortment strength has an
intermediate value under a range of migration-selection parameters, even in
diverged populations, due to subtle effects which depend sensitively on the
extent of phenotypic variation within these populations. The evolutionary
dynamics of the polygenic trait is studied using the hypergeometric and
infinitesimal models. We further investigate the sensitivity of our results to
the assumptions of the hypergeometric model, using individual-based simulations.
PMID- 28419448
TI - Understanding the Transfer Deficit: Contextual Mismatch, Proactive Interference,
and Working Memory Affect Toddlers' Video-Based Transfer.
AB - Researchers tested the impact of contextual mismatch, proactive interference, and
working memory (WM) on toddlers' transfer across contexts. Forty-two toddlers (27
34 months) completed four object-retrieval trials, requiring memory updating on
Trials 2-4. Participants watched hiding events on a tablet computer. Search
performance was tested using another tablet (match) or a felt board (mismatch).
WM was assessed. On earlier search trials, WM predicted transfer in both
conditions, and toddlers in the match condition outperformed those in the
mismatch condition; however, the benefit of contextual match and WM decreased
over trials. Contextual match apparently increased proactive interference on
later trials. Findings are interpreted within existing accounts of the transfer
deficit, and a combined account is proposed.
PMID- 28419449
TI - Pharmacogenetic association with neurotoxicity in Hispanic children with acute
lymphoblastic leukaemia.
PMID- 28419450
TI - Acquired blue sclerae in POEMS syndrome.
PMID- 28419451
TI - Do State Continuing Medical Education Requirements for Physicians Improve
Clinical Knowledge?
AB - OBJECTIVE: To evaluate the effect of state continuing medical education (CME)
requirements on physician clinical knowledge. DATA SOURCES: Secondary data for
19,563 general internists who took the Internal Medicine Maintenance of
Certification (MOC) examination between 2006 and 2013. STUDY DESIGN: We took
advantage of a natural experiment resulting from variations in CME requirements
across states over time and applied a difference-in-differences methodology to
measure associations between changes in CME requirements and physician clinical
knowledge. We measured changes in clinical knowledge by comparing initial and MOC
examination performance 10 years apart. We constructed difference-in-differences
estimates by regressing examination performance changes against physician
demographics, county and year fixed effects, trend-state indicators, and state
CME change indicators. DATA COLLECTION: Physician data were compiled by the
American Board of Internal Medicine. State CME policies were compiled from
American Medical Association reports. PRINCIPAL FINDINGS: More rigorous CME
credit-hour requirements (mostly implementing a new requirement) were associated
with an increase in examination performance equivalent to a shift in examination
score from the 50th to 54th percentile. CONCLUSIONS: Among physicians required to
engage in a summative assessment of their clinical knowledge, CME requirements
were associated with an improvement in physician clinical knowledge.
PMID- 28419452
TI - Associations Among Meaning in Life, Body Image, Psychopathology, and Suicide
Ideation in Spanish Participants With Eating Disorders.
AB - OBJECTIVE: The aims of this study were to (a) analyze whether participants with
eating disorders have lower meaning in life than the nonclinical population; (b)
discover whether participants with eating disorders with low meaning in life have
more body image disturbances, more psychopathology, and higher suicide ideation
than participants with high meaning in life; (c) analyze whether meaning in life
is associated with eating disorder psychopathology; and (d) analyze whether
meaning in life is able to predict eating disorder psychopathology and suicide
ideation, when body image is controlled. METHOD: The clinical sample comprised
247 Spanish participants diagnosed with eating disorders, and the nonclinical
sample comprised Spanish 227 participants. RESULTS: Participants with eating
disorders had lower meaning in life than the nonclinical population. Patients
with low meaning in life had higher psychopathology and suicide ideation than
participants with high meaning in life. Meaning in life was a significant
predictor of the eating disorder psychopathology and suicide ideation.
CONCLUSION: Low meaning in life is associated with eating disorder
psychopathology in a Spanish sample with eating disorders.
PMID- 28419453
TI - Obstetrics and gynecology physician knowledge of Rh immune globulin prophylaxis.
AB - BACKGROUND: Previous studies have shown that more than 20% of laboratories would
have recommended inaccurate doses of Rh immune globulin (RhIG) in hypothetical
cases. Efforts have been made in educating laboratories in correct dosing
calculations; however, obstetricians are most often responsible for ordering
RhIG. The objective of this study was to assess knowledge of RhIG indications and
dosing among obstetrics and gynecology (OB/GYN) physicians in the United States.
STUDY DESIGN AND METHODS: An anonymous 17- question online survey was distributed
to all OB/GYN resident and attending physicians affiliated with US residency
training programs. RESULTS: A total of 165 surveys were collected, with 139 fully
completed. Ninety-two percent of respondents correctly recognized the need for
RhIG in D- patients with negative antibody screens. In a scenario of a
fetomaternal hemorrhage (FMH) of 45 mL, only 22% of respondents correctly chose
the appropriate RhIG dosage. Of those who were correct, 10% had correctly
identified 30 mL as the amount of fetal whole blood covered by one dose of RhIG,
while 48% incorrectly identified 15 mL (n = 31). A total of 49.3% of respondents
reported residency as the most recent formal training on RhIG dosing and 35%
reported never (n = 140). CONCLUSIONS: Our study found that OB/GYN physicians are
knowledgeable regarding indications for RhIG immunoprophylaxis but were
insufficient at calculating dosages in cases of FMH. More standardized education
and training among OB/GYN physicians may decrease the risk of maternal
alloimmunization, in part because RhIG dosage recommendations from laboratories
are not standard practice.
PMID- 28419455
TI - Human Electrical Muscular Incapacitation and Effects on QTc Interval.
AB - Human Electrical Muscular Incapacitation (HEMI) is used to subdue combative
individuals. Changes in cardiac electrical activity have been proposed as the
cause of death in a small fraction of these individuals. The current study sought
to determine whether changes in QTc interval occur after HEMI exposure. Twenty
four participants had EKG readings before a 5-second HEMI exposure and within 30
min after exposure. All subject EKGs were read by a data-blinded cardiac
electrophysiologist who calculated a QT corrected (QTc) interval. QTc interval
was calculated using Bazett method. QTc prolongation was defined as >430 ms and a
threshold of 30 ms for identifying QTc lengthening. Five participants experienced
QTc prolongation and six had QTc lengthening. One participant developed QTc
prolongation exceeding 500 ms, which carries a risk of developing multifocal
ventricular tachycardia. These results suggest that HEMI exposure may cause EKG
changes with a risk of ventricular tachycardia.
PMID- 28419454
TI - The de novo autism spectrum disorder RELN R2290C mutation reduces Reelin
secretion and increases protein disulfide isomerase expression.
AB - Despite the recent identification of over 40 missense heterozygous Reelin gene
(RELN) mutations in autism spectrum disorder (ASD), none of these has been
functionally characterized. Reelin is an integral signaling ligand for proper
brain development and post-natal synapse function - properties likely disrupted
in ASD patients. We find that the R2290C mutation, which arose de novo in an
affected ASD proband, and other analogous mutations in arginine-amino acid
arginine domains reduce protein secretion. Closer analysis of RELN R2290C
heterozygous neurospheres reveals up-regulation of Protein Disulfide Isomerase
A1, best known as an endoplasmic reticulum-chaperone protein, which has been
linked to neuronal pathology. This effect is recapitulated in a heterozygous RELN
mouse mutant that is characterized by defective Reelin secretion. These findings
suggest that both a deficiency in Reelin signaling and pathologic impairment of
Reelin secretion may contribute to ASD risk.
PMID- 28419456
TI - Time-lapse lab-based x-ray nano-CT study of corrosion damage.
AB - An experimental protocol (workflow) has been developed for time-lapse x-ray
nanotomography (nano-CT) imaging of environmentally driven morphological changes
to materials. Two case studies are presented. First, the leaching of nanoparticle
corrosion inhibitor pigment from a polymer coating was followed over 14 days,
while in the second case the corrosion damage to an AA2099 aluminium alloy was
imaged over 12 hours. The protocol includes several novel aspects relevant to
nano-CT with the use of a combination of x-ray absorption and phase contrast data
to provide enhanced morphological and composition information, and hence reveal
the best information to provide new insights into the changes of different phases
over time. For the pigmented polymer coating containing nominally strontium
aluminium polyphosphate, the strontium-rich components within the materials are
observed to leach extensively whereas the aluminium-rich components are more
resistant to dissolution. In the case of AA2099 it is found that the initial
grain boundary corrosion is driven by the presence of copper-rich phases and is
then followed by the corrosion of grains of specific orientation.
PMID- 28419457
TI - Subscales of the Barratt Impulsiveness Scale differentially relate to the Big
Five factors of personality.
AB - The place of impulsiveness in multidimensional personality frameworks is still
unclear. In particular, no consensus has yet been reached with regard to the
relation of impulsiveness to Neuroticism and Extraversion. We aim to contribute
to a clearer understanding of these relationships by accounting for the
multidimensional structure of impulsiveness. In three independent studies, we
related the subscales of the Barratt Impulsiveness Scale (BIS) to the Big Five
factors of personality. Study 1 investigated the associations between the BIS
subscales and the Big Five factors as measured by the NEO Five-Factor Inventory
(NEO-FFI) in a student sample (N = 113). Selective positive correlations emerged
between motor impulsiveness and Extraversion and between attentional
impulsiveness and Neuroticism. This pattern of results was replicated in Study 2
(N = 132) using a 10-item short version of the Big Five Inventory. In Study 3, we
analyzed BIS and NEO-FFI data obtained from a sample of patients with
pathological buying (N = 68). In these patients, the relationship between motor
impulsiveness and Extraversion was significantly weakened when compared to the
non-clinical samples. At the same time, the relationship between attentional
impulsiveness and Neuroticism was substantially stronger in the clinical sample.
Our studies highlight the utility of the BIS subscales for clarifying the
relationship between impulsiveness and the Big Five personality factors. We
conclude that impulsiveness might occupy multiple places in multidimensional
personality frameworks, which need to be specified to improve the
interpretability of impulsiveness scales.
PMID- 28419458
TI - Therapeutic potential of novel formulated forms of curcumin in the treatment of
breast cancer by the targeting of cellular and physiological dysregulated
pathways.
AB - Breast cancer is among the most important causes of cancer related death in
women. There is a need for novel agents for targeting key signaling pathways to
either improve the efficacy of the current therapy, or reduce toxicity. There is
some evidence that curcumin may have antitumor activity in breast cancer. Several
clinical trials have investigated its activity in patients with breast cancer,
including a recent trial in breast cancer patients receiving radiotherapy, in
whom it was shown that curcumin reduced the severity of radiation dermatitis,
although it is associated with low bioavailability. Several approaches have been
developed to increase its absorption rate (e.g., nano crystals, liposomes,
polymers, and micelles) and co-delivery of curcumin with adjuvants as well as
different conjugation to enhance its bioavailability. In particular, micro
emulsions is an option for transdermal curcumin delivery, which has been reported
to increase its absorption. Lipid-based nano-micelles is another approach to
enhance curcumin absorption via gastrointestinal tract, while polymer-based nano
formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of
curcumin at a sustained level. This review summarizes the current data of the
therapeutic potential of novel formulations of curcumin with particular emphasis
on recent preclinical and clinical studies in the treatment of breast cancer.
PMID- 28419459
TI - How can we restrict the sale of sports and energy drinks to children? A proposal
for a World Health Organization-sponsored framework convention to restrict the
sale of sports and energy drinks.
AB - High-sugar drinks, including fruit drinks, soft drinks, sports drinks and energy
drinks, are of no nutritional value and contribute to the burden of dental
disease in all age groups. The manufacturers of sports and energy drinks have
elected to target children in their marketing campaigns and promote a misleading
association between their products, healthy lifestyles and sporting prowess. The
World Health Organization (WHO) has acknowledged that strategies aimed at
prevention of dental disease are the only economically viable options for
managing the oral health of children in low- and middle-income countries.
Developed nations will also be advantaged by preventive programmes given that the
cost of providing dental care to those who cannot pay draws valuable resources
away from more pressing health issues. The Convention on the Rights of the Child
(CRC) obligates governments to develop legislation to protect the health of
children. A framework convention modelled on the existing Framework Convention
for Tobacco Control, supported by the WHO, would assist governments to
proactively legislate to restrict the sale of sports and energy drinks to
children. This article will consider how a framework convention would be an
advantage with reference to the strategies used by sports and energy drink
manufacturers in Australia.
PMID- 28419460
TI - Land plants drive photorespiration as higher electron-sink: comparative study of
post-illumination transient O2 -uptake rates from liverworts to angiosperms
through ferns and gymnosperms.
AB - In higher plants, the electron-sink capacity of photorespiration contributes to
alleviation of photoinhibition by dissipating excess energy under conditions when
photosynthesis is limited. We addressed the question at which point in the
evolution of photosynthetic organisms photorespiration began to function as
electron sink and replaced the flavodiiron proteins which catalyze the reduction
of O2 at photosystem I in cyanobacteria. Algae do not have a higher activity of
photorespiration when CO2 assimilation is limited, and it can therefore not act
as an electron sink. Using land plants (liverworts, ferns, gymnosperms, and
angiosperms) we compared photorespiration activity and estimated the electron
flux driven by photorespiration to evaluate its electron-sink capacity at CO2
compensation point. In vivo photorespiration activity was estimated by the
simultaneous measurement of O2 -exchange rate and chlorophyll fluorescence yield.
All C3-plants leaves showed transient O2 -uptake after actinic light illumination
(post-illumination transient O2 -uptake), which reflects photorespiration
activity. Post-illumination transient O2 -uptake rates increased in the order
from liverworts to angiosperms through ferns and gymnosperms. Furthermore,
photorespiration-dependent electron flux in photosynthetic linear electron flow
was estimated from post-illumination transient O2 -uptake rate and compared with
the electron flux in photosynthetic linear electron flow in order to evaluate the
electron-sink capacity of photorespiration. The electron-sink capacity at the CO2
-compensation point also increased in the above order. In gymnosperms
photorespiration was determined to be the main electron-sink. C3-C4 intermediate
species of Flaveria plants showed photorespiration activity, which intermediate
between that of C3- and C4-flaveria species. These results indicate that in the
first land plants, liverworts, photorespiration started to function as electron
sink. According to our hypothesis, the dramatic increase in partial pressure of
O2 in the atmosphere about 0.4 billion years ago made it possible to drive
photorespiration with higher activity in liverworts.
PMID- 28419461
TI - Assent in Pediatric Patients.
AB - AIM: To report an analysis of the concept of pediatric assent. BACKGROUND: The
concept of assent is poorly defined in current literature which may lead to
potentially flawed practices in obtaining pediatric assent. DESIGN: The Walker
and Avant (2011) method is used to provide clarity to the concept of pediatric
assent. DATA SOURCES: Data were collected from PubMed, Academic Search Premier,
PhilPapers, Wikipedia, and Google. REVIEW METHODS: Data were collected from 2014
to 2015. Twenty-three sources published between 2011 and 2015, nine sources
published between 2003 and 2009, the Belmont Report (1979), and the American
Academy of Pediatrics' report (1995) were included for pertinent contributions to
this multidisciplinary concept analysis. RESULTS: Elements of assent include a
patient's thoughtful review of the proposed treatment and rational decision in
choosing the best course of action. There may be social, familial, and cognitive
development factors influencing this process. CONCLUSION: This framework uses
nurses' knowledge of cognitive development and ethics to inform practice. Assent
is respectful of minor patients and ensures their rights are protected. Policies
and procedures can be developed to incorporate assent, researchers have a
stronger conceptual base, and educators can train nurses to help pediatric
patients develop medical decision making skills.
PMID- 28419462
TI - Modeling and Simulation of Pivotal Clinical Trials Using Linked Models for
Multiple Endpoints in Chronic Obstructive Pulmonary Disease With Roflumilast.
AB - Roflumilast is a selective phosphodiesterase 4 inhibitor (PDE4i) for the
treatment of severe chronic obstructive pulmonary disease (COPD). In 2 large
phase 3 trials in a broader population of COPD patients (BY217/M2-111,
ClinicalTrials.gov: NCT00076089 and BY217/M2-112, ClinicalTrials.gov:
NCT00430729), treatment with roflumilast reduced the rate of exacerbations;
however, the reduction did not reach statistical significance. Two linked dose
response models for the primary (annualized COPD exacerbation counts) and
secondary (change from baseline in forced expiratory volume in 1 second [FEV1 ])
end points were therefore developed to characterize and quantify effect sizes and
the patient characteristics influencing them. The models showed that disease
severity and bronchitis, particularly the severity of bronchitis expressed in
cough-and-sputum scores, were good predictors of exacerbation rates and
differential benefit of roflumilast in exacerbation reduction. The models were
used to support the rational design of 2 phase 3 randomized, placebo-controlled
clinical trials (BY217/M2-124, ClinicalTrials.gov: NCT00297102 and BY217/M2-125,
ClinicalTrials.gov: NCT00297115) by identifying the most appropriate patient
population using clinical trial simulations. Model predictions for both end
points were found to be highly accurate - as confirmed by the results from these
trials, which led to the approval of roflumilast as the first oral PDE4i for the
treatment of COPD in patients associated with chronic bronchitis and a history of
exacerbations.
PMID- 28419463
TI - Profiling of anthocyanins in transgenic purple-fleshed sweet potatoes by HPLC
MS/MS.
AB - BACKGROUND: Anthocyanins in purple-fleshed sweet potato (PSP) are beneficial to
human health. The leaf color (Lc) gene is a transcription factor involved in
regulating anthocyanin biosynthesis. The anthocyanin profiles of wild-type PSP of
Ayamurasaki and its three Lc-transgenic lines were investigated by high
performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). In vitro
antioxidant activities of wild-type and Lc-transgenic lines, including reducing
power activity, DPPH radical scavenging activity, hydroxyl radical scavenging
activity, linoleic acid autoxidation inhibition activity, ABTS free radical
scavenging activity and oxygen radical absorbance capacity activity, were
measured. RESULTS: The results showed that the total anthocyanin contents
increased 1.5-1.9 times in three transgenic lines compared with that in wild-type
PSP. Seventeen anthocyanins were found in wild-type PSP, while 19 in Lc
transgenic lines including cyanidin-based, peonidin-based and pelargonidin-based
anthocyanins. Three pelargonidin-based anthocyanins were detected in three Lc
transgenic lines. Among them, the relative contents of cyanidin-based and
pelargonidin-based anthocyanins increased 1.9-2.0 and 3.4-4.5 times respectively,
while peonidin-based anthocyanins decreased 1.8-1.9 times in Lc-transgenic lines,
compared with wild-type PSP. PSP from wild-type Ayamurasaki and three Lc
transgenic lines exhibited potent antioxidant activities, whereas there was no
distinct difference among them. CONCLUSION: The transgene Lc significantly
increased the content of total anthocyanins and remarkably changed the
anthocyanin profiles in Ayamurasaki. Such novel and high content of anthocyanins
obtained in the Lc-transgenic lines with potent antioxidant activities may
provide unique functional products with potential helpful for human health. (c)
2017 Society of Chemical Industry.
PMID- 28419464
TI - A new species of Chrysobrycon (Characiformes, Characidae, Stevardiinae) from the
Amazon River basin in Colombia, with a new diagnostic characteristic for the
genus.
AB - Chrysobrycon mojicai sp. nov. is described from forest streams that are part of
the Amazon River basin in Colombia. It is distinguished from all congeners by
having most of the maxillary teeth with distal tips lateroventrally curved (v.
teeth straight along their lengths) and a greater number of dentary teeth (20-27
v. 11-19, except in Chrysobrycon yoliae). The posterior margin of the ventral
process of the quadrate does not reach the vertical through the posterior margin
of the symplectic and these features differentiate C. mojicai from Chrysobrycon
myersi and C. yoliae (v. posterior margin of ventral process of quadrate reaching
vertical through posterior margin of symplectic). In species of Chrysobrycon, the
frontals are extensively contacting each other along the midline, resulting in an
absent frontal fontanel and a reduced parietal fontanel. This extensive contact
between the frontals modifying the fontanels is a condition rarely found within
the Stevardiinae and hence is proposed as an additional diagnostic characteristic
for the genus. An updated identification key for all Chrysobrycon species is
provided.
PMID- 28419465
TI - Assessing PTSD in the military: Validation of a scale distributed to Danish
soldiers after deployment since 1998.
AB - Since 1998, soldiers deployed to war zones with the Danish Defense (~31,000) have
been invited to fill out a questionnaire on post-mission reactions. This provides
a unique data source for studying the psychological toll of war. Here, we
validate a measure of PTSD-symptoms from the questionnaire. Soldiers from two
cohorts deployed to Afghanistan with the International Security Assistance Force
(ISAF) in 2009 (ISAF7, N = 334) and 2013 (ISAF15, N = 278) filled out a standard
questionnaire (Psychological Reactions following International Missions, PRIM)
concerning a range of post-deployment reactions including symptoms of PTSD (PRIM
PTSD). They also filled out a validated measure of PTSD-symptoms in DSM-IV, the
PTSD-checklist (PCL). We tested reliability of PRIM-PTSD by estimating Cronbach's
alpha, and tested validity by correlating items, clusters, and overall scale with
corresponding items in the PCL. Furthermore, we conducted two confirmatory factor
analytic models to test the factor structure of PRIM-PTSD, and tested measurement
invariance of the selected model. Finally, we established a screening and a
clinical cutoff score by application of ROC analysis. We found high internal
consistency of the PRIM-PTSD (Cronbach's alpha = 0.88; both cohorts), strong item
item (0.48-0.83), item-cluster (0.43-0.72), cluster-cluster (0.71-0.82) and full
scale (0.86-0.88) correlations between PRIM-PTSD and PCL. The factor analyses
showed adequate fit of a one-factor model, which was also found to display strong
measurement invariance across cohorts. ROC curve analysis established cutoff
scores for screening (sensitivity = 1, specificity = 0.93) and clinical use
(sensitivity = 0.71, specificity = 0.98). In conclusion, we find that PRIM-PTSD
is a valid measure for assessing PTSD-symptoms in Danish soldiers following
deployment.
PMID- 28419466
TI - The 2016 revised World Health Organization definition of 'myelodysplastic
syndrome with isolated del(5q)'; prognostic implications of single versus double
cytogenetic abnormalities.
AB - The definition of the myelodysplastic syndrome (MDS) subtype 'MDS with isolated
del(5q)' was expanded to include cases with one additional non-chromosome 7 based
cytogenetic abnormality in the 2016 revised World Health Organization
classification. This study applied the revised definition to a large primary MDS
cohort, and evaluated the prognostic impact of the additional cytogenetic
abnormality. Seventy-two of 1067 patients (7%) met the 'MDS with isolated
del(5q)' criteria, 11 (1%) of whom had an additional cytogenetic abnormality.
There was no survival difference between patients in whom del(5q) occurred alone,
compared to those with one additional cytogenetic abnormality (P = 0.52).
PMID- 28419467
TI - Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and
Serum Biomarkers to Cimaglermin Alfa (GGF2) Clinical Trials.
AB - Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in
development for heart failure. Phase I trials were suspended when two cimaglermin
alfa-treated subjects experienced concomitant elevations in serum
aminotransferases and total bilirubin, meeting current US Food and Drug
Administration criteria for a serious liver safety signal (i.e., "Hy's Law"). We
assayed mechanistic biomarkers in archived clinical trial serum samples which
confirmed the hepatic origin of the aminotransferase elevations in these two
subjects and identified apoptosis as the major mode of hepatocyte death. Using a
mathematical model of drug-induced liver injury (DILIsym) and a simulated
population, we estimated that the maximum hepatocyte loss in these two subjects
was <13%, which would not result in liver dysfunction sufficient to significantly
increase serum bilirubin levels. We conclude that the two subjects should not be
considered Hy's Law cases and that mechanistic biomarkers and modeling can aid in
refining liver safety risk assessment in clinical trials.
PMID- 28419468
TI - Activation of the Akt-CREB signalling axis by a proline-rich heptapeptide confers
resistance to stress-induced cell death and inflammation.
AB - Cell stress of various kinds can lead to the induction of cell death and a
damaging inflammatory response. Hence, a goal of therapeutic cell-stress
management is to develop agents that might effectively regulate undesirable cell
death and inflammation. To that end, we developed a synthetic peptide of seven
amino acids based on structural mimicry to a functional domain of p53, a key
factor in the responses of cells to stressful stimuli. This heptapeptide, which
we term Stressin-1, was found to inhibit both cell death and the secretion of
inflammatory mediators by various cell types in response to different stressful
agents in vitro. The combined anti-inflammatory and anti-apoptotic activities of
Stressin-1 were associated with a cellular signalling cascade that induced
activation of Akt kinase and activation of the cAMP response element-binding
protein (CREB) transcription factor. These immediate signalling events led to the
inhibition of the signal transducer and activator of transcription and nuclear
factor-kappaB pathways 24 hr later. Unexpectedly, we found no evidence for a
direct involvement of p53 in the effects produced by Stressin-1. Intraperitoneal
administration of 100 MUg of Stressin-1 to lethally irradiated mice significantly
protected them from death. These findings show that activating the Akt-CREB axis
with Stressin-1 can counteract some of the undesirable effects of various cell
stresses. Stressin-1 may have clinical usefulness.
PMID- 28419469
TI - The endoplasmic reticulum-associated protein, OS-9, behaves as a lectin in
targeting the immature calcium-sensing receptor.
AB - The mechanisms responsible for the processing and quality control of the calcium
sensing receptor (CaSR) in the endoplasmic reticulum (ER) are largely unknown. In
a yeast two-hybrid screen of the CaSR C-terminal tail (residues 865-1078), we
identified osteosarcoma-9 (OS-9) protein as a binding partner. OS-9 is an ER
resident lectin that targets misfolded glycoproteins to the ER-associated
degradation (ERAD) pathway through recognition of specific N-glycans by its
mannose-6-phosphate receptor homology (MRH) domain. We show by confocal
microscopy that the CaSR and OS-9 co-localize in the ER in COS-1 cells. In
immunoprecipitation studies with co-expressed OS-9 and CaSR, OS-9 specifically
bound the immature form of wild-type CaSR in the ER. OS-9 also bound the immature
forms of a CaSR C-terminal deletion mutant and a C677A mutant that remains
trapped in the ER, although binding to neither mutant was favored over wild-type
receptor. OS-9 binding to immature CaSR required the MRH domain of OS-9
indicating that OS-9 acts as a lectin most likely to target misfolded CaSR to
ERAD. Our results also identify two distinct binding interactions between OS-9
and the CaSR, one involving both C-terminal domains of the two proteins and the
other involving both N-terminal domains. This suggests the possibility of more
than one functional interaction between OS-9 and the CaSR. When we investigated
the functional consequences of altered OS-9 expression, neither knockdown nor
overexpression of OS-9 was found to have a significant effect on CaSR cell
surface expression or CaSR-mediated ERK1/2 phosphorylation.
PMID- 28419470
TI - Excessive heat-associated gingival necrosis: a case report.
AB - Heat-delivery devices have been associated with relatively high temperatures.
Previous basic research studies suggest that the risk for periodontal tissues is
negligible, as the presence of the root filling materials, amongst other factors,
reduce the risk of overheating. This report describes the case of a 45 year old
male, who was undergoing restorative treatment in a multi-specialty dental
practice. As part of his overall treatment planning, orthograde root canal
retreatment for his maxillary left incisor teeth was deemed necessary, due to
chronic apical periodontitis. Following cold lateral compaction, the coronal
portion of the core material was severed using a System B Heat Source (Kerr
Dental, Orange, CA, USA), with the patient reporting pain as well as a burning
sensation. The following day the patient was seen by a periodontist and gingival
necrosis in relation to the central incisor was found. The most likely cause of
the complication was considered to be excessive heat during the operative
procedure. The patient was followed up for a 2-year period and the soft tissues
returned to their original condition without the need for periodontal treatment.
PMID- 28419471
TI - Spectral analysis of the stick-slip phenomenon in "oral" tribological texture
evaluation.
AB - : "Oral" tribology has become a new paradigm in food texture studies to
understand complex texture attributes, such as creaminess, oiliness, and
astringency, which could not be successfully characterized by traditional texture
analysis nor by rheology. Stick-slip effects resulting from intermittent sliding
motion during kinetic friction of oral mucosa could constitute an additional
determining factor of sensory perception where traditional friction coefficient
values and their Stribeck regimes fail in predicting different lubricant (food
bolus and saliva) behaviors. It was hypothesized that the observed jagged
behavior of most sliding force curves are due to stick-slip effects and depend on
test velocity, normal load, surface roughness as well as lubricant type.
Therefore, different measurement set-ups were investigated: sliding velocities
from 0.01 to 40 mm/s, loads of 0.5 and 2.5 N as well as a smooth and a textured
silicone contact surface. Moreover, dry contact measurements were compared to
model food systems, such as water, oil, and oil-in-water emulsions. Spectral
analysis permitted to extract the distribution of stick-slip magnitudes for
specific wave numbers, characterizing the occurrence of jagged force peaks per
unit sliding distance, similar to frequencies per unit time. The spectral
features were affected by all the above mentioned tested factors. Stick-slip
created vibration frequencies in the range of those detected by oral
mechanoreceptors (0.3-400 Hz). The study thus provides a new insight into the use
of tribology in food psychophysics. PRACTICAL APPLICATIONS: Dynamic spectral
analysis has been applied for the first time to the force-displacement curves in
"oral" tribology. Analyzing the stick-slip phenomenon in the dynamic friction
provides new information that is generally overlooked or confused with machine
noise and which may help to understand friction-related sensory attributes. This
approach allows us to differentiate samples that have similar friction
coefficient, but are perceived differently in the mouth. The next step of our
research will be to combine spectral attributes, such as the magnitudes of
specific wave number bands and possibly their evolution during sliding, together
with friction coefficient and viscosity values of foods with sensory results. The
highest potential lies in predicting smoothness in opposition to roughness of a
surface, such as a rough tongue when eating astringent or dry foods, or of
particles when eating grainy foods. The effects of food ingredients at the nano
to macroscales can then be used to optimize a specific lubrication behavior.
PMID- 28419472
TI - Hepatic expression of oncogenes Bmi1 and Dkk1 is up-regulated in hepatitis B
virus surface antigen-transgenic mice and can be induced by treatment with HBV
particles or lipopolysaccharides in vitro.
AB - Previous studies have shown that hepatocellular carcinoma (HCC) develops more
frequently in hepatitis B virus surface antigen (HBsAg)-transgenic mice (Alb/HBs)
than in wild-type (WT) mice. However, the mechanism of this HCC model has not
been well documented. Toll-like receptor 4 (Tlr4) signaling probably links innate
immunity and HCC progression. This study was designed to investigate the role of
innate immunity in hepatocarcinogenesis in Alb/HBs mice. Immunohistochemical
analysis of liver specimens from Alb/HBs mice (16 per group) showed that the
oncogenes Bmi1 (16/16, 100%) and Dkk1 (13/16, 81.25%) were highly expressed in
Alb/HBs mice, whereas the other oncogenes evaluated were expressed in smaller
percentages of mice (Afp, 9/16, 56.2%; Ctnnb1, 5/16, 31.3%; Epcam, 0/16; 0%).
Comparable results were obtained by quantitative PCR analysis. Hepatic gene
expression of Tlr2, Tlr4, Il6 and Tnf was additionally elevated in Alb/HBs mice.
Stimulation of primary murine hepatocytes with cell culture-derived HBV particles
or LPS increased the expression of oncogenes (Bmi1, Dkk1) and inflammatory
factors (Tnf, Il6, Tlr4). Proliferation and colony formation of hepatoma cells
were enhanced by treatment with HBV and LPS and were impaired by the suppression
of Bmi1 and Dkk1 by small interfering RNAs. Substantial induction of BMI1 and
DKK1 was found in liver biopsy samples from patients with HBV-related HCC but not
in HCC samples without HBV infection background. These findings suggest that
innate immunity may link inflammation and tumor progression during chronic HBV
infection, involving the oncogenes BMI1 and DKK1.
PMID- 28419474
TI - Using Advances From Cognitive Behavioral Models of Anxiety to Guide Treatment for
Social Anxiety Disorder.
AB - This case features an adult male with moderate social anxiety disorder and mild
depressive symptoms who showed an initial positive response to an earlier
experience of cognitive behavior therapy, but then relapsed when he started
avoiding social situations again because of continuing beliefs that experiencing
anxiety was unacceptable. His treatment at our clinic focused on shifting
unhelpful thinking about the likelihood and consequences of becoming anxious and
reengaging in avoided social situations so he could learn to tolerate negative
affect and uncertainty. The treatment approach draws from cognitive behavioral
models of social anxiety and highlights advances in clinical science, especially
recent work on the causal role of interpretation biases (the tendency to assign
negative or threatening meaning to ambiguous situations) in the maintenance and
reduction of anxiety.
PMID- 28419473
TI - Translating the Cognitive Model of PTSD to the Treatment of Very Young Children:
A Single Case Study of an 8-Year-Old Motor Vehicle Accident Survivor.
AB - Posttraumatic stress disorder (PTSD) is a clinical condition that occurs after a
discrete traumatic event, such as an accident or assault. Research into PTSD has
primarily been adult-focused; however, there is a growing body of evidence
evaluating the theory and treatment of PTSD in young children. Consequently,
cognitive behavior therapy (CBT) interventions for PTSD in youth have been
developed that focus on 3 core components of the cognitive model-a disorganized
memory of the trauma, maladaptive appraisals of the trauma and its effects
(meanings), and dysfunctional coping mechanisms (management). Here, we describe
the extension of this treatment approach (termed CBT-3M) to very young children
(3-8 years) through the case of Dylan, an 8-year-old motor vehicle accident
survivor. This serves as an illustration of the underlying theory and its
successful application. Further work is intended to provide evidence of the
efficacy of this treatment via an ongoing treatment trial.
PMID- 28419475
TI - Fruit and vegetable intake and prostate cancer risk in the European Prospective
Investigation into Cancer and Nutrition (EPIC).
AB - Several dietary factors have been studied in relation to prostate cancer;
however, most studies have not reported on subtypes of fruit and vegetables or
tumor characteristics, and results obtained so far are inconclusive. This study
aimed to examine the prospective association of total and subtypes of fruit and
vegetable intake with the incidence of prostate cancer overall, by grade and
stage of disease, and prostate cancer death. Lifestyle information for 142,239
men participating in the European Prospective Investigation into Cancer and
Nutrition from 8 European countries was collected at baseline. Multivariable Cox
regression models were used to estimate hazard ratios (HRs) and 95% confidence
intervals (CIs). After an average follow-up time of 13.9 years, 7,036 prostate
cancer cases were identified. Compared with the lowest fifth, those in the
highest fifth of total fruit intake had a significantly reduced prostate cancer
risk (HR = 0.91; 95% CI = 0.83-0.99; p-trend = 0.01). No associations between
fruit subtypes and prostate cancer risk were observed, except for citrus fruits,
where a significant trend was found (HR = 0.94; 95% CI = 0.86-1.02; p-trend =
0.01). No associations between total and subtypes of vegetables and prostate
cancer risk were observed. We found no evidence of heterogeneity in these
associations by tumor grade and stage, with the exception of significant
heterogeneity by tumor grade (pheterogeneity <0.001) for leafy vegetables. No
significant associations with prostate cancer death were observed. The main
finding of this prospective study was that a higher fruit intake was associated
with a small reduction in prostate cancer risk. Whether this association is
causal remains unclear.
PMID- 28419477
TI - The effectiveness of riboflavin and ultraviolet light pathogen reduction
technology in eliminating Trypanosoma cruzi from leukoreduced whole blood.
AB - BACKGROUND: The parasitic Chagas disease is caused by the protozoan Trypanosoma
cruzi, which is mainly transmitted by insect vectors. Other infection routes,
both in endemic and in nonendemic areas, include organ and marrow
transplantation, congenital transmission, and blood transfusion. Asymptomatic
chronic chagasic individuals may have a low and transient parasitemia in
peripheral blood and, consequently, they can unknowingly transmit the disease via
blood transfusion. Riboflavin and ultraviolet (UV) light pathogen reduction is a
method to reduce pathogen transfusion transmission risk based on damage to the
pathogen nucleic acids. STUDY DESIGN AND METHODS: In this study, we tested the
effectiveness of this technology for the elimination of T. cruzi parasites in
artificially contaminated whole blood units (WBUs) and thus for decreasing the
risk of T. cruzi transfusion transmission. The contaminated WBUs were
leukoreduced by filtration and treated with riboflavin and UV light. The level of
pathogen reduction was quantified by a real-time polymerase chain reaction (qPCR)
and a real-time reverse transcription-polymerase chain reaction (RT-qPCR) as a
viability assay. RESULTS: The RNA (cDNA) quantification of the parasites showed a
more than 99% reduction of viable T. cruzi parasites after leukoreduction and a
complete reduction (100%) after the riboflavin and UV light treatment.
CONCLUSION: Riboflavin and UV light treatment and leukoreduction used in
conjunction appears to eliminate significant amounts of viable T. cruzi in whole
blood. Both strategies could complement other blood bank measures already
implemented to prevent the transmission of T. cruzi via blood transfusion.
PMID- 28419478
TI - Exposure to the American flag polarizes democratic-republican ideologies.
AB - Some prior research has suggested that exposure to the American flag tilts
Americans towards Republicanism, while others have proffered that it brings outs
a common 'together' perspective instead. We explore a third possibility - that it
may actually polarize Americans' political ideology. It is generally accepted
that exposure to an environmental cue can shift attitudes and behaviours, at
least partly or temporarily, in a manner that is consistent with that cue. Yet,
the same cue can mean different things to different people. In the same vein,
given how national identity and political ideology are intertwined in the United
States, we hypothesize that the American flag should heighten different political
beliefs depending on individuals' political ideology. To Democrats, being
American is to support Democratic values, but to Republicans, being American is
to support Republican values. The American flag thus should heighten Democrats of
their Democratic identity, and it should heighten Republicans of their Republican
one. The results of an experiment with 752 American respondents who were
representative of the US population supported this polarizing effect of the
American flag. The theoretical and policy implications of the findings are
offered.
PMID- 28419476
TI - Cortactin, a Lyn substrate, is a checkpoint molecule at the intersection of BCR
and CXCR4 signalling pathway in chronic lymphocytic leukaemia cells.
AB - Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an
actin cytoskeletal regulatory role involved in cell migration and cancer
progression following its phosphorylation at Y421. We recently demonstrated that
Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL).
This work was aimed at defining the functional role of Cortactin in these
patients. We found that Cortactin is variably expressed in CLL patients both in
the peripheral blood and lymph nodes and that its expression correlates with the
release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic
cells. Cortactin knockdown, by siRNA, induced a reduction in MMP-9 release as
well as a decrease of migration capability of leukaemic B cells in vitro, also
after chemotactic stimulus. Furthermore, Cortactin phosphorylation was lowered by
the Src kinase-inhibitor PP2 with a consequent decrease of MMP-9 release in
culture medium. An impaired migration, as compared to control experiments without
Cortactin knockdown, was observed following CXCL12 triggering. Reduced Cortactin
expression and phosphorylation were also detected both in vivo and in vitro after
treatment with Ibrutinib, a Btk inhibitor. Our results highlight the role of
Cortactin in CLL as a check-point molecule between the BCR and CXCR4 signalling
pathways.
PMID- 28419479
TI - Sonographic diagnosis of a radiographically occult displaced fracture of a costal
cartilage.
AB - We report the case of a 22-year-old athlete who sustained a blunt thoracic trauma
to the right chest causing a costal cartilage fracture. Plain radiographs
revealed no abnormalities while sonographic (US) examination performed a week
later because of persistent pain led to the diagnosis of a displaced fracture of
the right tenth costal cartilage. A follow-up US examination confirmed the
healing of the fracture and allowed the patient to return to competitive sport
activity. We recommend the use of US in patients with persisting pain after
thoracic trauma with negative plain radiographs of the ribs to rule out
radiographically occult costal cartilage fractures. (c) 2017 Wiley Periodicals,
Inc. J Clin Ultrasound 45:605-607, 2017.
PMID- 28419480
TI - Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib
Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and
Simulation Approach.
AB - Neutropenia is the most commonly reported hematologic toxicity following
treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for
metastatic breast cancer. Using data from 185 advanced cancer patients receiving
palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was
developed to describe the time course of absolute neutrophil count (ANC) and
quantify the exposure-response relationship for neutropenia. These analyses help
in understanding neutropenia associated with palbociclib and its comparison with
chemotherapy-induced neutropenia. In the model, palbociclib plasma concentration
was related to its antiproliferative effect on precursor cells through drug
related parameters (ie, maximum estimated drug effect and concentration
corresponding to 50% of the maximum effect), and neutrophil physiology was
mimicked through system-related parameters (ie, mean transit time, baseline ANC,
and feedback parameter). Sex and baseline albumin level were significant
covariates for baseline ANC. It was demonstrated by different model evaluation
approaches (eg, prediction-corrected visual predictive check and standardized
visual predictive check) that the final model adequately described longitudinal
ANC with good predictive capability. The established model suggested that higher
palbociclib exposure was associated with lower longitudinal neutrophil counts.
The ANC nadir was reached approximately 21 days after palbociclib treatment
initiation. Consistent with their mechanisms of action, neutropenia associated
with palbociclib (cytostatic) was rapidly reversible and noncumulative, with a
notably weaker antiproliferative effect on precursor cells relative to
chemotherapies (cytotoxic). This pharmacokinetic-pharmacodynamic model aids in
predicting neutropenia and optimizing dosing for future palbociclib trials with
different dosing regimen combinations.
PMID- 28419481
TI - Are induced fit protein conformational changes caused by ligand-binding
predictable? A molecular dynamics investigation.
AB - In this work, the ability of molecular dynamics simulations (MD) to prospectively
predict regions of ligand binding sites that could undergo induced fit effects
was investigated. Conventional MD was run on 39 apo structures (no ligand), and
the resulting trajectories were compared to a set of 147 holo X-ray structures
(ligand-bound). It was observed from the simulations, in the absence of the
ligands, that structures exhibiting large residue conformational changes
indicated higher likelihood of induced fit effects. Nevertheless, the simulation
results did not perform better than using the normalized crystallographic
structural factors as predictors of active-site rigid residues (87% predictive
power) and mobile residues (47% predictive power). While the simulations could
not produce full active sites conformations similar to holo-like states, it was
found that the simulations could reproduce bound state conformations of
individual residues. These results suggest potential issues in the use of
unligated simulation frames directly for drug design applications such as ligand
docking, and an overall caution in the use of protein flexibility in docking
protocols should be emphasized. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419482
TI - FMEA of manual and automated methods for commissioning a radiotherapy treatment
planning system.
AB - PURPOSE: To evaluate the level of risk involved in treatment planning system
(TPS) commissioning using a manual test procedure, and to compare the associated
process-based risk to that of an automated commissioning process (ACP) by
performing an in-depth failure modes and effects analysis (FMEA). METHODS: The
authors collaborated to determine the potential failure modes of the TPS
commissioning process using (a) approaches involving manual data measurement,
modeling, and validation tests and (b) an automated process utilizing application
programming interface (API) scripting, preloaded, and premodeled standard
radiation beam data, digital heterogeneous phantom, and an automated
commissioning test suite (ACTS). The severity (S), occurrence (O), and
detectability (D) were scored for each failure mode and the risk priority numbers
(RPN) were derived based on TG-100 scale. Failure modes were then analyzed and
ranked based on RPN. The total number of failure modes, RPN scores and the top 10
failure modes with highest risk were described and cross-compared between the two
approaches. RPN reduction analysis is also presented and used as another
quantifiable metric to evaluate the proposed approach. RESULTS: The FMEA of a MTP
resulted in 47 failure modes with an RPNave of 161 and Save of 6.7. The highest
risk process of "Measurement Equipment Selection" resulted in an RPNmax of 640.
The FMEA of an ACP resulted in 36 failure modes with an RPNave of 73 and Save of
6.7. The highest risk process of "EPID Calibration" resulted in an RPNmax of 576.
CONCLUSIONS: An FMEA of treatment planning commissioning tests using automation
and standardization via API scripting, preloaded, and pre-modeled standard beam
data, and digital phantoms suggests that errors and risks may be reduced through
the use of an ACP.
PMID- 28419483
TI - Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill
Multiple-Trauma Patients at the Usual Dosage and a New Proposal for
Administration.
AB - The pharmacokinetic profile of intravenous acetaminophen administered to
critically ill multiple-trauma patients was studied after 4 consecutive doses of
1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60,
90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected
(during 6-hour intervals between doses) to determine serum and urine
acetaminophen concentrations. These were used to calculate the following
pharmacokinetic parameters: maximum and minimum concentrations, terminal half
life, area under serum concentration-time curve from 0 to 6 hours, mean residence
time, volume of distribution, and serum and renal clearance of acetaminophen.
Daily doses of acetaminophen required to obtain steady-state minimum (bolus
dosing) and average plasma concentrations (continuous infusion) of 10 MUg/mL were
calculated (10 MUg/mL is the presumed lower limit of the analgesic range). Data
are expressed as median [interquartile range]. Twenty-two patients were studied,
mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84]
kg). Acetaminophen concentrations and pharmacokinetic parameters were these:
maximum concentration 33.6 [25.7-38.7] MUg/mL and minimum concentration 0.5 [0.2
2.3] MUg/mL, all values below 10 MUg/mL and 8 below the detection limit; half
life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7]
MUg.h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of
distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7]
L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady
state minimum concentration of 10 MUg/mL would be 12.2 [7.8-16.4] g/day (166 [112
202] mg/[kg.day]); for an average steady-state concentration of 10 MUg/mL, they
would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg.day]). In conclusion,
administration of acetaminophen at the recommended dosage of 1 g per 6 hours to
critically ill multiple-trauma patients yields serum concentrations below 10
MUg/mL due to increased elimination. To reach the 10 MUg/mL target, and from a
strictly pharmacokinetic point of view, continuous infusion may be more feasible
than bolus dosing. Such a change in dosing strategy requires appropriate,
pharmacokinetic-pharmacodynamic and specific safety study.
PMID- 28419484
TI - Variations in the functional visual field for detection of lung nodules on chest
computed tomography: Impact of nodule size, distance, and local lung complexity.
AB - PURPOSE: To explore the characteristics that impact lung nodule detection by
peripheral vision when searching for lung nodules on chest CT-scans. METHODS:
This study was approved by the local IRB and is HIPAA compliant. A simulated
primary (1 degrees ) target mass (2 * 2 * 5 cm) was embedded into 5 cm thick
subvolumes (SV) extracted from three unenhanced lung MDCT scans (64 row, 1.25 mm
thickness, 0.7 mm increment). One of 30 solid, secondary nodules with either 3-4
mm and 5-8 mm diameters were embedded into 192 of 207 SVs. The secondary nodule
was placed at a random depth within each SV, a transverse distance of 2.5, 5,
7.5, or 10 mm, and along one of eight rays cast every 45 degrees from the center
of the 1 degrees mass. Video recordings of transverse paging in cranio-caudal
direction were created for each SV (frame rate three sections/sec). Six
radiologists observed each cine-loop once while gaze-tracking hardware assured
that gaze was centered on the 1 degrees mass. Each radiologist assigned a
confidence rating (0-5) to the detection of a secondary nodule and indicated its
location. Detection sensitivity was analyzed relative to secondary nodule size,
transverse distance, radial orientation, and lung complexity. Lung complexity was
characterized by the number of particles (connected pixels) and the sum of the
area of all particles above a -500 HU threshold within regions of interest around
the 1 degrees mass and secondary nodule. RESULTS: Using a proportional odds
logistic regression model and eliminating redundant predictors, models fit
individually to each reader resulted in the following decreasing order of
association based on greatest reduction in Akaike Information Criterion:
secondary nodule diameter (6/6 readers, P < 0.001), distance from central mass
(6/6 readers, P < 0.001), lung complexity particle count (5/6 readers, P = 0.05),
and lung complexity particle area (3/6 readers, P = 0.03). Substantial inter
reader differences in sensitivity to decreasing nodule diameter, distance, and
complexity characteristics were observed. CONCLUSIONS: Of the investigated
parameters, secondary nodule size, distance from the gaze center and lung
complexity (particle number and area) significantly impact nodule detection with
peripheral vision.
PMID- 28419485
TI - Maternal and Child Characteristics Associated With Mother-Child Interaction in
One-Year-Olds.
AB - Mothers' interactions with their young children have predicted later child
development, behavior, and health, but evidence has been developed mainly in at
risk clinical samples. An economically and racially diverse sample of pregnant
women who were not experiencing a high-risk pregnancy were recruited to
participate in a community-based, longitudinal study of factors associated with
child cognitive and social-emotional development during the first 3 years. The
purpose of the present analysis was to identify associations between the
characteristics of 1125 mothers and their 1-year-olds and the mothers' and
children's scores on the Nursing Child Assessment Teaching Scale (NCATS). A
multivariable approach was used to identify maternal and child characteristics
associated with NCATS scores and to develop prediction models for NCATS total and
subscale scores of mothers and children. Child expressive and receptive
communication and maternal IQ, marital status, age, and insurance predicted NCATS
Mother total score, accounting for 28% of the score variance. Child expressive
communication and birth weight predicted the NCATS Child total score, accounting
for 4% of variance. Child's expressive communication and mother's IQ and marital
status predicted NCATS mother-child total scores. While these findings were
similar to reports of NCATS scores in at-risk populations, no previous teams
examined all of the mother and child characteristics included in this analysis.
These findings support the utility of the NCATS for assessing mother-child
interaction and predicting child outcomes in community-based, non-clinical
populations. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419487
TI - The Effect of Medicaid Physician Fee Increases on Health Care Access,
Utilization, and Expenditures.
AB - OBJECTIVE: To evaluate the effect of Medicaid fee changes on health care access,
utilization, and spending for Medicaid beneficiaries. DATA SOURCE: We use the
2008 and 2012 waves of the Medical Expenditure Panel Survey linked to state-level
Medicaid-to-Medicare primary care reimbursement ratios obtained through surveys
conducted by the Urban Institute. We also incorporate data from the Current
Population Survey and the Area Resource Files. STUDY DESIGN: Using a control
group made up of the low-income privately insured, we conduct a difference-in
differences analysis to assess the relationship between Medicaid fee changes and
access to care, utilization of health care services, and out-of-pocket medical
expenditures for Medicaid enrollees. PRINCIPAL FINDINGS: We find that an increase
in the Medicaid-to-Medicare payment ratio for primary care services results in an
increase in outpatient physician visits, emergency department utilization, and
prescription fills, but only minor improvements in access to care. In addition,
we report an increase in total annual out-of-pocket expenditures and spending on
prescription medications. CONCLUSIONS: Compared to the low-income privately
insured, increased primary care reimbursement for Medicaid beneficiaries leads to
higher utilization and out-of-pocket spending for Medicaid enrollees.
PMID- 28419486
TI - Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients:
Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age
Range.
AB - This population analysis described the pharmacokinetics of bortezomib after twice
weekly, repeat-dose, intravenous administration in pediatric patients
participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in
relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981)
trial in de novo acute myelogenous leukemia. The sources of variability in the
pharmacokinetic parameters were characterized and quantified to support dosing
recommendations. Patients received intravenous bortezomib 1.3 mg/m2 twice-weekly,
on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11
of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood
samples were obtained and the plasma was harvested on day 8 over 0-72 hours
postdose to measure bortezomib concentrations by liquid chromatography-tandem
mass spectrometry. Concentration-time data were analyzed by nonlinear mixed
effects modeling. Covariates were examined using forward addition (P <
.01)/backward elimination (P < .001). Data were included from 104 patients
(49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2
11 years/12-16 years). Bortezomib pharmacokinetics were described by a 3
compartment model with linear elimination. Body surface area adequately accounted
for variability in clearance (exponent 0.97), supporting body surface area-based
dosing. Stratified visual predictive check simulations verified that neither age
group nor patient population represented sources of meaningful pharmacokinetic
heterogeneity not accounted for by the final population pharmacokinetic model.
Following administration of 1.3 mg/m2 intravenous bortezomib doses, body surface
area-normalized clearance in pediatric patients was similar to that observed in
adult patients, thereby indicating that this dose achieves similar systemic
exposures in pediatric patients.
PMID- 28419488
TI - Interferon lambda3 gene (IL28B) is associated with spontaneous or treatment
induced viral clearance in hepatitis C virus-infected multitransfused patients
with thalassemia.
AB - BACKGROUND: Hepatitis C virus (HCV) is the major posttransfusion infection in
multitransfused individuals in India with thalassemia major. To our knowledge,
this study is the first conducted to correlate and comprehend the effects of the
host interleukin (IL)28B gene polymorphism at loci rs12979860 and rs8099917 in
spontaneous or interferon (IFN)-induced treatment response in the HCV
seroreactive individuals with thalassemia major. STUDY DESIGN AND METHODS: A
total of 557 HCV-seroreactive individuals with thalassemia were processed for HCV
viral genotyping and host IL28B single-nucleotide polymorphism analysis at loci
rs12979860 and rs8099917. RESULTS: Of 557 individuals, 70.92% were found to be
HCV RNA positive with Genotype 3 (95.18%) as predominant strain. A favorable CC
allele at locus rs2979860 and TT allele at rs8099917 were 75.31 and 77.16%,
respectively, which was strongly associated with spontaneous clearance of
infection (p < 0.05). Of 85 IFN-treated cases, 56 achieved sustained virologic
response (SVR) whereas 27 were relapsed cases. Among these patients who achieved
SVR, a favorable CC/TT allele at rs12979860/rs8099917 was found to be predominant
with 76.79 and 66.07%, respectively, whereas in the case of relapsed patients,
unfavorable CT (55.56%) and TG (59.26%) alleles were found to be predominant.
Additionally, low serum ferritin level was significantly associated with SVR.
CONCLUSION: CC at rs12979860 and TT at rs8099917 was strongly associated with
spontaneous clearance and SVR in the population with thalassemia. Low age group
and low serum ferritin level are important cofactors. This allelic pattern will
aid clinicians in making an informed decision about prognosis and therapeutic
management.
PMID- 28419490
TI - European cowpea landraces for a more sustainable agriculture system and novel
foods.
AB - BACKGROUND: Genetic diversity is fundamental to breeding programs and
consequently has an important role in obtaining new varieties. To properly use
the genetic diversity present in germplasm collections, a good knowledge of the
agro-morphological traits of each accession is needed. The aim of this study was
to explore the production capacity of 24 cowpea landraces from southern Europe,
through phenotypic characterization and evaluation in three different locations
in Greece and Portugal. RESULTS: Most qualitative parameters tested showed a high
stability among the three locations. A wide difference was observed among the
three locations with respect to number of days to flowering, ranging from 55 to
99 days. Quantitative traits showed a higher genotype * environment than genetic
variance component. In general, an inverse relationship between sigma2ge /sigma2g
ratio (where sigma2ge is genotype * genotype interaction and sigma2g is genotype
impact) and heritability value was observed. Principal component analysis was
able to group accessions based on their origin. The first two principal
components explained 97.52% of variation, being the number of seeds per plant,
plant height and seed protein content, the traits which contributed most to
variability. CONCLUSION: The results show that sufficient variation exists in
different traits within landraces in the studied cowpea germplasm to pursue a
breeding program. However, the quantitative traits showed a higher genotype *
environment component. (c) 2017 Society of Chemical Industry.
PMID- 28419491
TI - Intrinsic neural activity differences among psychotic illnesses.
AB - Individuals with psychosis have been reported to show either reduced or augmented
brain responses under seemingly similar conditions. It is likely that
inconsistent baseline-adjustment methods are partly responsible for this
discrepancy. Using steady-state stimuli during a pro/antisaccade task, this study
addressed the relationship between nonspecific and stimulus-related neural
activity, and how these activities are modulated as a function of cognitive
demands. In 98 psychosis probands (schizophrenia, schizoaffective disorder, and
bipolar disorder with psychosis), neural activity was assessed during baseline
and during a 5-s period in preparation for the pro/antisaccade task. To maximize
the ability to identify meaningful differences between psychosis subtypes,
analyses were conducted as a function of subgrouping probands by standard
clinical diagnoses and neurobiological features. These psychosis "biotypes" were
created using brain-based biomarkers, independent of symptomatology (Clementz et
al., ). Psychosis probands as a whole showed poor antisaccade performance and
diminished baseline oscillatory phase synchrony. Psychosis biotypes differed on
both behavioral and brain measures, in ways predicted from Clementz et al. ().
Two biotype groups showed similarly deficient behavior and baseline synchrony,
despite diametrically opposed neural activity amplitudes. Another biotype
subgroup was more similar to healthy individuals on behavioral and brain
measures, despite the presence of psychosis. This study provides evidence that
(a) consideration of baseline levels of activation and synchrony will be
essential for a comprehensive understanding of neural response differences in
psychosis, and (b) distinct psychosis subgroups exhibit reduced versus augmented
intrinsic neural activity, despite cognitive performance and clinical
similarities.
PMID- 28419492
TI - Expression and trafficking of MR1.
AB - MHC class I-related gene protein (MR1) is a non-polymorphic MHC class IB antigen
presenting molecule that is the restricting molecule for mucosal-associated
invariant T (MAIT) cells, a prominent population of innate-like antibacterial T
cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation,
with the MR1 ligand derived from vitamin B compounds or their metabolic
precursors. Many bacteria and some fungi produce the activating ligand for MR1.
In evolution, MR1 is highly conserved in most, but not all, mammals. In humans
and rodents it is expressed in a broad range of cell types, both haematopoietic
and non-haematopoietic, although cell surface expression has been difficult to
detect. Although MR1 trafficking shares features with both the MHC class I and
MHC class II pathways, it is distinct. Several strands of evidence suggest that
the intracellular location where MR1 is loaded differs for soluble ligand and for
ligand derived from intact bacteria. The regulation of MR1 surface expression may
also vary between different cell types. This paper will review what is currently
known about the expression and trafficking of MR1 and propose a model for the
loading and trafficking of MR1.
PMID- 28419493
TI - Distribution of the tick Dermacentor reticulatus in the United Kingdom.
AB - The recent implication of Dermacentor reticulatus (Ixodida: Ixodidae) in the
transmission of canine babesiosis in the U.K. has highlighted the lack of
accurate published data on its distribution in this country. This paper aims to
collate and appraise historical data for D. reticulatus, to supplement such data
with more recent surveillance data and to report on field sampling conducted
during 2009-2016. These updated data facilitate better understanding of the
current distribution of this tick in the U.K., which will better inform disease
risk assessments. There appear to be four known regions of the U.K. in which D.
reticulatus currently occurs, including western Wales, North and South Devon, and
Essex. The majority of foci are located in coastal sand dunes and maritime
grasslands, including grazing marsh. However, more recently the tick has been
detected in urban greenspace in Essex. The emergence of this tick as a vector of
babesiosis in the U.K. and its recent apparent spread in Essex into urban
greenspace highlight the need for continued surveillance and for further research
into its status as a vector of human and veterinary pathogens.
PMID- 28419494
TI - Increased levels of soluble CD163 in periodontitis patients.
AB - AIM: Soluble CD163 (sCD163) has been implicated as a new biomarker in
inflammatory conditions. The aim of this cross-sectional study was to assess
CD163 levels systemically and locally in patients with chronic periodontitis.
METHODS: sCD163 levels were measured by ELISA in serum samples from 70
periodontitis and 70 periodontally healthy subjects, and in saliva samples in a
subset of the population. Two gingival biopsies were harvested per subject from
20 periodontitis patients: one from a periodontally affected site, the other from
a healthy site, and the relative expression of CD163 mRNA was assessed by real
time PCR. RESULTS: Serum sCD163 was significantly higher in periodontitis
patients compared to periodontally healthy subjects (720.0 +/- 330.6 ng/ml versus
510.7 +/- 219.6 ng/ml, respectively; p < .001). Similarly, sCD163 levels in
saliva were significantly increased in periodontitis compared to healthy subjects
(3.01 +/- 5.07 ng/ml versus 1.98 +/- 4.95 ng/ml, respectively; p = .009). Serum
and saliva sCD163 levels showed a positive correlation (Kendall's tau .27, p =
.018). Importantly, CD163 gene expression was significantly higher in affected
sites compared to unaffected sites in periodontitis patients, with a mean fold
upregulation of 9.9 (STD: 15.3, p = .010). CONCLUSION: Our findings suggest that
CD163 may be involved in the pathogenesis of periodontitis and its link with
systemic conditions.
PMID- 28419495
TI - Giant proliferating trichilemmal cyst arising from a nevus sebaceus growing for
30 years.
AB - Nevus sebaceus of Jadassohn, a congenital cutaneous hamartoma, has the potential
to develop into various epidermal adnexal-origin neoplasms. While the most common
neoplasms are trichoblastoma or syringocystadenoma, proliferating trichilemmal
cysts are exceptionally rare. We report a case of a 63-year-old Cuban male with a
giant proliferating trichilemmal cyst arising from a nevus sebaceus on the right
shoulder which had been growing for 30 years. Proliferating trichilemmal cysts
arising from nevus sebaceus cases are difficult to diagnose clinically and
histologically as they are very rare and have not been defined by exact
diagnostic criteria. Our case creates awareness of this particular tumor in nevus
sebaceus and shares clinical and histological diagnostic information that can be
used to make a proper diagnosis.
PMID- 28419496
TI - Emotionally Focused Couple Therapy for Parents Raising a Child with an Autism
Spectrum Disorder: A Pilot Study.
AB - Many couples raising children diagnosed with an Autism Spectrum Disorder (ASD)
are often resilient in confronting unique parental demands, while others
experience greater risk for relational distress. Research has shown that
Emotionally Focused Couple Therapy (EFT) is efficacious with couples raising
chronically ill children and relevant to the relational demands of parents of
children diagnosed with an ASD. This pilot study tested the effectiveness of EFT
with seven couples presenting with moderate to severe distress, who were also
parents of a child diagnosed with an ASD. Results demonstrated significant
decreases in marital distress at posttreatment and 6-month follow-up. The study
also identified several unique themes associated with couple distress and the
parenting experiences of this population.
PMID- 28419498
TI - Perceptions and Experiences of Marriage Preparation Among U.S. Muslims: Multiple
Voices from the Community.
AB - Although Muslims in the United States are a growing population, there is limited
research on their relational patterns and how they prepare for marriage. We
conducted in-depth interviews with 32 members of the Muslim community in
Southeast Michigan including married individuals, divorced individuals,
therapists, and imams (Muslim religious leaders) to explore their perceptions and
experiences of marriage preparation. Our analysis revealed that marriage
preparation varies but is less likely to involve a requirement of premarital
counseling, with imams being the primary providers, not therapists. Barriers to
participation include stigma, lack of awareness, logistical and financial
challenges, and parental influence. Partnerships between imams and therapists,
and family and community efforts are necessary to address barriers and increase
participation in premarital education programs.
PMID- 28419497
TI - Predictors of long-term outcomes in patients undergoing periodontal maintenance.
AB - AIM: This retrospective study aimed to characterize the baseline status of
patients following periodontal maintenance, analysing the association between the
long-term outcome of these patients, smoking, bruxism, and the main clinical and
radiographic variables. MATERIAL AND METHODS: A sample of 174 patients with
moderate to severe periodontitis was refined into homogeneous subsamples
according to smoking and bruxism and the rate of tooth loss due to periodontal
disease (TLPD): 0, 1-2, and >2 teeth. The association and the distribution (chi2
test) of the variables within the subsamples were analysed. RESULTS: Smoking and
bruxism were significantly associated with higher TLPD rates. Vertical and
circumferential bone defects (p < .0001), and abfractions (p < .0001) were
associated with bruxism and particularly with bruxism and TLPD >2. Furcation
defects (p = .0002), fewer radio-opaque subgingival calculus (chi2 p < .0001), a
lower mean Gingival index (chi2 p = .027), and increased mean recessions >1.5 mm
(chi2 p = .0026) were associated with smoking and higher TLPD rates. The mean
baseline mobility, abfractions, and recessions characterized two basic types of
TLPD. CONCLUSIONS: Smoking, bruxism, and routine clinical and radiological
parameters can be used to characterize the baseline status of patients with worse
outcomes.
PMID- 28419499
TI - Periodontitis changes renal structures by oxidative stress and lipid
peroxidation.
AB - OBJECTIVE: The aim of this study was to investigate whether experimental
periodontitis cause changes to the renal tissues and imbalance in oxidative
stress in kidneys. METHODS: Twenty-two female Wistar rats were separated into two
groups: control and periodontitis. We assessed the following parameters: gingival
bleeding index (GBI), tooth mobility, gum malondialdehyde (MDA), myeloperoxidase
(MPO) activity, probing pocket depth (PPD), alveolar bone loss (ABL) for
periodontal tissues; histomorphometric measures associated with renal corpuscle
and histopathological aspects (evaluation of brush border) for kidneys; as also
blood and urine biomarkers. Finally, we evaluated renal oxidative stress through
glutathione (GSH) and MDA respectively. RESULTS: With regard to renal
histomorphometry, significant differences were observed in all parameters
assessed. In relation periodic acid Schiff (PAS) staining, disruption was
observed of brush border in the periodontitis group in the renal tubules in
comparison with the control group. The periodontitis group presented
significantly higher MDA and lower GSH concentrations in the kidneys compared
with animals without periodontitis. CONCLUSION: The induced periodontitis caused
histomorphometric changes in renal tissues as well as disruption of the brush
border in renal tubules, alterations associated with increase in oxidative stress
in kidneys. However, these alterations were not sufficient to cause differences
in the renal function markers.
PMID- 28419500
TI - Antepartum management and obstetric outcomes among pregnancies with Down syndrome
from diagnosis to delivery.
AB - OBJECTIVE: Little is known about the obstetric care of an ongoing pregnancy with
trisomy 21. We sought to ascertain an obstetric profile for pregnancies with Down
syndrome to help guide prenatal management. METHOD: Pregnancies managed for
delivery with trisomy 21 between 2003 and 2014 were analyzed. We reviewed
demographic data, diagnostic testing, prenatal surveillance, obstetric outcomes,
and placental pathology. T-test, chi-squared test, and Fisher correction were
used as indicated. RESULTS: Sixty-eight pregnancies were identified, and four
women (5.9%) experienced a loss during the pregnancy. Among the remaining 64
pregnancies, the average gestational age at delivery was 36.9 weeks, growth
restriction was present in 12 (17.5%), and major anomalies were present in 51
(75.0%). Delivery was undertaken for non-reassuring fetal surveillance in 35.9%
of the pregnancies; 93% of which represented a change from prior reassuring
surveillance and 52.6% of which demonstrated histopathologic evidence of
placental insufficiency. None among increased maternal age, the presence of an
anomaly, or growth restriction were significantly more common in the group with
non-reassuring surveillance. CONCLUSION: There are high rates of fetal growth
restriction, delivery for non-reassuring fetal status, and evidence of placental
insufficiency among affected pregnancies, suggesting a role for antepartum
surveillance. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419501
TI - Stakeholders' views of the introduction of assistive technology in the classroom:
How family-centred is Australian practice for students with cerebral palsy?
AB - BACKGROUND: With family-centred care widely recognized as a cornerstone for
effective assistive technology service provision, the current study was
undertaken to investigate to what extent such approaches were used by schools
when assistive technology assessments and implementation occurred in the
classroom. METHOD: In this cross-sectional study, we compare survey results from
parents (n = 76), school staff (n = 33) and allied health professionals (n = 65)
with experience in the use of high-tech assistive technology. Demographic
characteristics and the stakeholders' perceived helpfulness and frequency
attending assessment and set-up sessions were captured. To evaluate how family
centred the assistive technology services were perceived to be, the parents
filled out the Measure of Processes of Care for Caregivers, and the professionals
completed the Measure of Processes of Care for Service Providers. Descriptive
statistics and one-way analysis of variance were used to conduct the data
analysis. RESULTS: Findings show that parents are more involved during the
assessment stage than during the implementation and that classroom teachers are
often not involved in the initial stage. Speech pathologists in particular are
seen to be to a great extent helpful when implementing assistive technology in
the classroom. This study found that family-centred service is not yet fully
achieved in schools despite being endorsed in early intervention and disability
services for over 20 years. No statistically significant differences were found
with respect to school staff and allied health professionals' roles, their years
of experience working with students with cerebral palsy and the scales in the
Measure of Processes of Care for Service Providers. CONCLUSION: To enhance the
way technology is matched to the student and successfully implemented, classroom
teachers need to be fully involved in the whole assistive technology process. The
findings also point to the significance of parents' involvement, with the support
of allied health professionals, in the process of selecting and implementing
assistive technology in the classroom.
PMID- 28419502
TI - Nuchal translucency measurement, free beta-hCG and PAPP-A concentrations in
IVF/ICSI pregnancies: systematic review and meta-analysis.
AB - So far, data on the effect of assisted reproductive technologies (ART) on the
components of first trimester combined screening for Down syndrome are still
controversial. A systematic search of the literature was performed in order to
identify the effect of ART, particularly in vitro fertilization (IVF) and
intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal
translucency, free beta-human chorionic gonadotrophin and pregnancy-associated
plasma protein-A measurements. Moreover, a meta-analysis and a descriptive
graphical representation of the ratios between ART and spontaneous pregnancies
(controls) values of median of the multiple of median (m0 MoM) were performed.
Free beta-human chorionic gonadotrophin test showed slightly higher values in the
ICSI group than controls (RR = 1.09, 95%CI: 1.03-1.16) but not in the IVF group
(RR = 1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for
IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI
0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal
translucency measurement did not show any statistical differences between study
groups (IVF and ICSI) and controls (RR = 1.00, 95%CI: 0.94-1.08 and RR = 1.01,
95%CI: 0.97-1.05, respectively). These results may be due to alterations in the
placentation of ART pregnancies. Differentiating further subgroups of ART
pregnancies may explain the differences in biomarker concentrations, in prenatal
behavior and in obstetric outcomes between ART and spontaneous pregnancies. (c)
2017 John Wiley & Sons, Ltd.
PMID- 28419503
TI - Comparison of the quantitative dry culture methods with both conventional media
and most probable number method for the enumeration of coliforms and Escherichia
coli/coliforms in food.
AB - : Sanita-kunTM CC (coliform count) and EC (Escherichia coli/coliform count),
sheet quantitative culture systems which can avoid chromogenic interference by
lactase in food, were evaluated in comparison with conventional methods for these
bacteria. Based on the results of inclusivity and exclusivity studies using 77
micro-organisms, sensitivity and specificity of both Sanita-kunTM met the
criteria for ISO 16140. Both media were compared with deoxycholate agar, violet
red bile agar, Merck ChromocultTM coliform agar (CCA), 3M PetrifilmTM CC and EC
(PEC) and 3-tube MPN, as reference methods, in 100 naturally contaminated food
samples. The correlation coefficients of both Sanita-kunTM for coliform detection
were more than 0.95 for all comparisons. For E. coli detection, Sanita-kunTM EC
was compared with CCA, PEC and MPN in 100 artificially contaminated food samples.
The correlation coefficients for E. coli detection of Sanita-kunTM EC were more
than 0.95 for all comparisons. There were no significant differences in all
comparisons when conducting a one-way analysis of variance (anova). Both Sanita
kunTM significantly inhibited colour interference by lactase when inhibition of
enzymatic staining was assessed using 40 natural cheese samples spiked with
coliform. Our results demonstrated Sanita-kunTM CC and EC are suitable
alternatives for the enumeration of coliforms and E. coli/coliforms,
respectively, in a variety of foods, and specifically in fermented foods.
SIGNIFICANCE AND IMPACT OF THE STUDY: Current chromogenic media for coliforms and
Escherichia coli/coliforms have enzymatic coloration due to breaking down of
chromogenic substrates by food lactase. The novel sheet culture media which have
film layer to avoid coloration by food lactase have been developed for
enumeration of coliforms and E. coli/coliforms respectively. In this study, we
demonstrated these media had comparable performance with reference methods and
less interference by food lactase. These media have a possibility not only to be
useful alternatives but also to contribute for accurate enumeration of these
bacteria in a variety of foods, and specifically in fermented foods.
PMID- 28419504
TI - Sensory and rheological characteristics of thickened liquids differing
concentrations of a xanthan gum-based thickener.
AB - : The objectives of this study were to develop and compare sensory
characteristics of beverages and soups thickened with different concentrations of
a xanthan gum-based thickener, and to examine, using rheological measurement,
whether the viscosity of the thickened liquids conformed to the recommendations
of the National Dysphagia Diet (NDD) Task Force. Beverages tested included water,
apple juice, orange juice, soymilk, and Yakult. The thickening agent was added to
samples at concentrations of 1, 2, or 3%. Addition of the thickening agent had a
significant effect on the appearance, texture, and starchy flavor, which were
evaluated by descriptive sensory evaluation. The reference standards of viscosity
used in sensory descriptive analysis could be useful to practitioners who have to
make dysphagia diets and need to learn to make them properly. In rheological
measurement, viscosity of thickened liquids in stationary state would be
perceived as higher compared to that while swallowing, because of the shear
thinning property. This could lead to noncompliance of the medical advice or
malnutrition. It is necessary to determine optimal proportion of xanthan gum
based thickener or uncover alternatives, which have shear thinning properties
lower than those of xanthan gum, for the acceptance of dysphagia patients. There
was no pudding-like viscosity as classified by NDD, when prepared following
instructions. Future studies should include higher concentrations of thickener to
find out the concentration of the thickener resulting in pudding-like viscosity
as recommended by NDD. PRACTICAL APPLICATIONS: When a manufacturer modifies or
develops a xanthan gum-based thickener, findings from this study can be utilized
to understand sensory and rheological characteristics of thickened liquid. For
practitioners who have to make dysphagia diets, the reference standards of
viscosity used in sensory descriptive analysis could be helpful for deciding the
viscosity level of thickened liquids based only on visual evaluation. This study
suggests manufacturers should provide clear direction for viscosity range and
thickener concentration. Medical doctors should pay close attention to the risk
of aspiration when prescribing pudding-like viscosity. Dietitians should
understand the variability in achieving different levels of viscosity and should
educate preparers who are responsible for making dysphagia meals.
PMID- 28419505
TI - Assisted Dying & Disability.
AB - This article explores at least two dominant critiques of assisted dying from a
disability rights perspective. In spite of these critiques, I conclude that
assisted dying ought to be permissible. I arrive at the conclusion that if we
respect and value people with disabilities, we ought to permit assisted dying. I
do so in the following manner. First, I examine recent changes in legislation
that have occurred since the Royal Society of Canada Expert Panel on End-of-Life
Decision-Making report, published in this journal. I suggest that these changes
are likely to only strengthen opposition to assisted dying from disability rights
activists and people with disabilities. Second, I focus on respect for people
with disabilities and in particular, respect for their autonomy and decision
making abilities. Third, I explore the opposition to assisted dying that focuses
on risk and the vulnerability of people with disabilities. Here I suggest that
this risk ought not to be of special concern. Ultimately, I conclude that
upholding respect for the disabled requires the legalization of assisted dying,
rather than the denial of access in a misguided effort to protect people with
disabilities.
PMID- 28419506
TI - Neuronal loss, demyelination and volume change in the multiple sclerosis
neocortex.
AB - AIMS: Indices of brain volume [grey matter, white matter (WM), lesions] are being
used as outcomes in clinical trials of patients with multiple sclerosis (MS). We
investigated the relationship between cortical volume, the number of neocortical
neurons estimated using stereology and demyelination. METHODS: Nine MS and seven
control hemispheres were dissected into coronal slices. On sections stained for
Giemsa, the cortex was outlined and optical disectors applied using systematic
uniform random sampling. Neurons were counted using an oil immersion objective (*
60) following stereological principles. Grey and WM demyelination was outlined on
myelin basic protein immunostained sections, and expressed as percentages of
cortex and WM respectively. RESULTS: In MS, the mean number of neurons was 14.9
+/- 1.9 billion vs. 24.4 +/- 2.4 billion in controls (P < 0.011), a 39%
difference. The density of neurons was smaller by 28% (P < 0.001) and cortical
volume by 26% (P = 0.1). Strong association was detected between number of
neurons and cortical volume (P < 0.0001). Demyelination affected 40 +/- 13% of
the MS neocortex and 9 +/- 12% of the WM, however, neither correlated with
neuronal loss. Only weak association was detected between number of neurons and
WM volume. CONCLUSION: Neocortical neuronal loss in MS is massive and strongly
predicted by cortical volume. Cortical volume decline detected in vivo may be
similarly indicative of neuronal loss. Lack of association between neuronal
density and demyelination suggests these features are partially independent, at
least in chronic MS.
PMID- 28419507
TI - A rapid solvent accessible surface area estimator for coarse grained molecular
simulations.
AB - The rapid and accurate calculation of solvent accessible surface area (SASA) is
extremely useful in the energetic analysis of biomolecules. For example, SASA
models can be used to estimate the transfer free energy associated with
biophysical processes, and when combined with coarse-grained simulations, can be
particularly useful for accounting for solvation effects within the framework of
implicit solvent models. In such cases, a fast and accurate, residue-wise SASA
predictor is highly desirable. Here, we develop a predictive model that estimates
SASAs based on Calpha-only protein structures. Through an extensive comparison
between this method and a comparable method, POPS-R, we demonstrate that our new
method, Protein-C alpha Solvent Accessibilities or PCASA, shows better
performance, especially for unfolded conformations of proteins. We anticipate
that this model will be quite useful in the efficient inclusion of SASA-based
solvent free energy estimations in coarse-grained protein folding simulations.
PCASA is made freely available to the academic community at
https://github.com/atfrank/PCASA. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419508
TI - Experience of carrier couples identified through a population-based carrier
screening pilot program for four founder autosomal recessive diseases in Saguenay
Lac-Saint-Jean.
AB - : A pilot population-based carrier screening program started in 2010 in the
Saguenay-Lac-Saint-Jean region of Quebec, Canada, for four recessive diseases
with local founder effects (tyrosinemia type I, autosomal recessive spastic
ataxia of Charlevoix-Saguenay, congenital lactic acidosis, and Andermann
syndrome). OBJECTIVES: The objective of this study was to describe the experience
of carrier couples identified through this program. METHODS: Semi-structured
interviews were performed with carrier couples. Thematic analysis of interview
transcripts was performed to identify emerging themes. RESULTS: Interviews were
performed with 15 carrier couples (56% response rate). Carrier couples had little
knowledge about the target diseases before being identified as carriers, despite
pre-test education sessions. The main motivation for screening was a
recommendation by a peer who had been screened, even for those with a positive
family history of one of the target conditions. Couples perceived themselves at
low risk of being a carrier couple, whatever their family history. Being found to
be a carrier couple was initially a shock, illustrating how ill prepared they
were for such a result, but carrier couples appreciated knowing their status.
CONCLUSION: Our results emphasize the informational needs of couples to make
informed decisions and the importance of post-test counseling for those with
positive results. Our findings can inform counseling procedures in expanded
carrier screening. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419509
TI - Automatic diagnosis of vulvovaginal candidiasis from Pap smear images.
AB - Vulvovaginal candidiasis (VVC) is the most common genital infections that are
seen every day in clinics. This infection is due to excessive growth of Candida
that are normally present in the vagina in small numbers. Diagnosis of VVC is
routinely done by direct microscopy of Pap smear samples and searching for the
Candida in the Pap smear glass slides. This manual method is subjective, time
consuming, labour-intensive and tedious. This study presents a computer-aided
diagnostic (CAD) method to improve human diagnosis of VVC. The proposed CAD
method reduces the diagnostic time and also can be worked as a second objective
opinion for pathologists. Our main objective is detection and extraction of
mycelium and conidium of Candida fungus from microscopic images of Pap smear
samples. In this regard, the proposed method is composed of three main phases,
namely preprocessing, segmentation, feature extraction and classification. At the
first phase, bottom-hat filtering is used for elimination of the cervical cells
and separating the background. Then decorrelation stretching and colour K-means
clustering are used for Candida segmentation. Finally the extracted features used
by a decision tree classifier to detect Candida from other parts of smear. The
proposed method was evaluated on 200 Pap smear images and showed specificity of
99.83% and 99.62% and sensitivity of 92.18% and 94.53% for detection of mycelium
and conidium, respectively.
PMID- 28419511
TI - Analysis of the variability of food texture properties: Application to the
fracturability of dry pet food.
AB - : An original stochastic finite element method (SFEM) is proposed for the texture
analysis of food products for which samples cannot be standardized. SFEM is able
to distinguish shape and texture variability. As an illustration, the methodology
is applied to dry cat food using compression testing. First, a deterministic
damage elastic model depending on six mechanical and three size parameters is
shown to fit adequately experimental data. Then, Morris screening method is
applied to FEM data: this highlights that the variability of compression tests is
significantly affected by two mechanical and two size parameters. Finally, the
nonlinear variability of each control variable is estimated from Sobol indices
derived from a time-efficient stochastic collocation method. These highlight that
the contribution of size parameters to test variability is about 20%. Therefore,
a robust estimation of the probability density function of texture properties can
be obtained for improved quality control, which outperforms current methods.
PRACTICAL APPLICATIONS: Food texture is affected by their material property and
geometrical structure. Material properties are difficult to estimate when the
size and shape of the samples cannot be standardized, for example, for snack or
pet food. In addition, the intrinsic variability of material properties due to
the recipe and the process cannot be neglected. But this cannot be easily
distinguished from the variability of geometrical parameters using conventional
methods. An innovative approach using stochastic finite element method is
developed and is able to exhibit the major parameters influencing the variability
of the response to mechanical testing. This methodology may be helpful to improve
acceptance sampling control procedures, for example, by combining texture and
size measurements when necessary, or by better determining the most robust
response variables for decision-making.
PMID- 28419510
TI - Increase of aquaporin 9 expression in astrocytes participates in astrogliosis.
AB - Here we assess the potential functional role of increased aquaporin 9 (APQ9) in
astrocytes. Increased AQP9 expression was achieved in primary astrocyte cultures
by transfection of a plasmid-containing green fluorescent protein fused to either
wild-type or mutated human AQP9. Increased AQP9 expression and phosphorylation at
Ser222 were associated with a significant change in astrocyte morphology, mainly
with a higher number of processes. Similar phenotypic changes are observed in
astrogliosis processes after injury. In parallel, we observed that in vivo,
thrombin preconditioning before ischemic stroke induced an early increase in AQP9
expression in the male mouse brain. This increased AQP9 expression was also
associated with astrocyte morphological changes, especially in the white matter
tract. Astrocyte reactivity is debated as being either beneficial or deleterious.
As thrombin preconditioning leads to a decrease in lesion size after stroke, our
data suggest that the early increase in AQP9 concomitant with astrocyte
reactivity leads to a beneficial effect. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419512
TI - Predicting receptor functionality of signaling lymphocyte activation molecule for
measles virus hemagglutinin by docking simulation.
AB - Predicting susceptibility of various species to a virus assists assessment of
risk of interspecies transmission. Evaluation of receptor functionality may be
useful in screening for susceptibility. In this study, docking simulation was
conducted for measles virus hemagglutinin (MV-H) and immunoglobulin-like variable
domain of signaling lymphocyte activation molecule (SLAM-V). It was observed that
the docking scores for MV-H and SLAM-V correlated with the activity of SLAM as an
MV receptor. These results suggest that the receptor functionality may be
predicted from the docking scores of virion surface proteins and cellular
receptor molecules.
PMID- 28419513
TI - Genetic Recombination Between Stromal and Cancer Cells Results in Highly
Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.
AB - The tumor microenvironment (TME) promotes tumor growth and metastasis. We
previously established the color-coded EL4 lymphoma TME model with red
fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green
fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested
an important role of stromal cells in lymphoma progression and metastasis. In the
present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal
cells to identify yellow-fluorescent genetically recombinant cells appearing only
during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in
C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell
transplantation. The subcutaneous tumors were harvested and transplanted to the
abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node,
ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells
and GFP-host cells, genetically recombinant yellow-fluorescent cells, were
observed only in the ascites and bone marrow. These results indicate genetic
exchange between the stromal and cancer cells. Possible mechanisms of genetic
exchange are discussed as well as its ramifications for metastasis. J. Cell.
Biochem. 118: 4216-4221, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419514
TI - Activation of TLR7 Inhibition of Mycobacterium Tuberculosis Survival by Autophagy
in RAW 264.7 Macrophages.
AB - The aim of the study was to evaluate the effect of regulation of TLR7 on
Mycobacterium tuberculosis (Mtb) survival in macrophages. TLR7 expression in
macrophages infected by Mtb was detected by RT-PCR and Western blotting.
Regulation of TLR7 was achieved by single strand RNA (ssRNA) or siRNA. The
effects of TLR7 on Mtb survival and cell viability were detected by acid fast
staining and cell counting kit-8, respectively. Cell ultrastructure was observed
via transmission electron microscopy (TEM), and autophagy related protein LC3 was
analyzed by Western blotting. TLR7 in Mtb infected macrophages was up-regulated
and up-regulation of TLR7 could eliminate intracellular Mtb. Up-regulation of
TLR7 could increase viability of Mtb infected cells, while down-regulation of
TLR7 induced decrease of cell viability compared with the controls. Autophagosome
was significantly increased in the Mtb infected macrophages after up-regulation
of TLR7 and LC3-II protein showed obvious increase compared with the controls.
Autophagosome could not be detected in macrophages after down-regulation of TLR7,
rough endoplasmic reticulum was dilated, and nuclear week gap was widened.
Moreover, LC3-II protein was reduced in Mtb infected macrophages based upon the
down-regulation of TLR7. Up-regulation of TLR7 could eliminate intracellular Mtb
through autophagy. J. Cell. Biochem. 118: 4222-4229, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28419515
TI - Incivility in the Online Classroom: A Guide for Policy Development.
AB - The growth of online education has created a learning environment that permits
nontraditional students the opportunity for degree completion without the burden
of relocation. Given the shortage of nurses at all educational levels, many
institutions of higher learning have created online programs to meet the needs of
both the student and the profession as a whole. Although convenient for the
student and beneficial for the nursing profession, the online learning
environment can present numerous challenges. Among these challenges are acts of
student incivility-creating a difficult work environment for faculty and, at
times, negatively affecting other students. Therefore, the purpose of this
article is to review problems associated with student incivility and share the
experience in creating as well as implementing a professionalism policy that
addresses student incivility. Recommendations for policy creation are summarized.
PMID- 28419516
TI - Systemic and local anti-nociceptive effects of simvastatin in the rat formalin
assay: Role of peroxisome proliferator-activated receptor gamma and nitric oxide.
AB - This study aimed to determine the potential systemic and local anti-nociceptive
effects of simvastatin (SIM) and the possible role of peroxisome proliferator
activated receptor gamma (PPARgamma) and nitric oxide (NO) pathways using a
formalin assay in rats. After allocation, rats were intraplantarly (i.pl.)
treated with formalin solution (2.5%) and the flinching behaviors were recorded
for 5 min (phase 1) and 15-60 min (phase 2). SIM was given intraperitoneally
(i.p.) and i.pl. 30 and 20 min before test, respectively. Intraperitoneal
administration of SIM attenuated the flinching number during both phases of the
test. This effect of i.p. SIM was significantly reduced by L -NAME (NO synthase
blocker, i.p.), but was augmented by L -arginine (NO precursor, i.p.) during both
phases of the formalin assay. Moreover, the antinociception caused by i.p. SIM
was blocked by GW-9662 (PPARgamma antagonist) at dose 2 mg/kg (i.p.). In another
experiment, concurrent ip administration of non-effective dose of simvastatin (5
mg/kg) with pioglitazone (PPARgamma agonist; 10, 20 mg/kg) produced
antinociception. However, pre-treatment with i.p. GW-9662 inhibited the enhanced
antinociceptive effect of pioglitazone on SIM during the phase 2 of formalin
assay. Results also showed that i.pl. SIM alone had no anti-nociceptive effects.
However, significant anti-nociception was observed when SIM (i.pl.) co
administered with non-effective dose of pioglitazone. Moreover, the enhanced
effect was antagonized by pre-treatment with i.pl. GW-9662. Our data suggest that
SIM produced antinociception through systemic but not local route of
administration in rats. Moreover, the antinociceptive effect of SIM is partly
mediated through PPARgamma receptors and NO pathway. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28419517
TI - Comparative analysis between RQ-PCR and digital droplet PCR of BCL2/IGH gene
rearrangement in the peripheral blood and bone marrow of early stage follicular
lymphoma.
AB - BCL2/IGH rearrangements were analysed by polymerase chain reaction (PCR) at
diagnosis in paired peripheral blood (PB) and bone marrow (BM) samples from 67
patients with stage I/II follicular lymphoma (FL). Real time quantitative PCR (RQ
PCR) and digital droplet PCR (ddPCR) were performed in cases with a major
breakpoint region (MBR+) at diagnosis and after localized radiotherapy and
rituximab administration in order to investigate the applicability of ddPCR. The
overall ddPCR/RQ-PCR concordance was 81.9% (113/138 samples) and 97.5% in the
40/138 with quantifiable disease (RQ-PCR>=10-5 ). At baseline, ddPCR allowed the
recovery of a MBR+ marker in 8/18 (44.4%) samples that resulted MBR
negative/minor cluster region-negative/minor BCL2-negative by qualitative PCR.
Moreover, the tumour burden at diagnosis significantly predicted progression-free
survival (PSF) only when quantified by ddPCR. Paired PB and BM samples analysis
demonstrated a high concordance in the detection of BCL2/IGH+ cells by
qualitative and quantitative methods; in particular, 40/62 samples were positive
by ddPCR (25 PB+/BM+; 9 PB+/BM-; 6 PB-/BM+), with 34/40 (85%) identified by the
study of PB only. In conclusion, in localized FL, ddPCR is a promising tool for
monitoring minimal residual disease (MRD) that is at least comparable to RQ-PCR
and potentially more accurate. PB is a suitable source for serial BCL2/IGH MRD
assessments, regardless of the methodology utilized.
PMID- 28419518
TI - Public preferences on written informed consent for low-risk pragmatic clinical
trials in Spain.
AB - AIMS: Pragmatic randomized clinical trials (pRCTs) collect data that have the
potential to improve medical care significantly. However, these trials may be
undermined by the requirement to obtain written informed consent, which can
decrease accrual and increase selection bias. Recent data suggest that the
majority of the US public endorses written consent for low-risk pRCTs. The
present study was designed to assess whether this view is specific to the US.
METHODS: The study took the form of a cross-sectional, probability-based survey,
with a 2 * 2 factorial design, assessing support for written informed consent vs.
verbal consent or general notification for two low-risk pRCTs in hypertension,
one comparing two drugs with similar risk/benefit profiles and the other
comparing the same drug being taken in the morning or at night. The primary
outcome measures were respondents' personal preference and hypothetical
recommendation to a research ethics committee regarding the use of written
informed consent vs. the alternatives. RESULTS: A total of 2008 adults sampled
from a probability-based online panel responded to the web-based survey conducted
in May 2016 (response rate: 61%). Overall, 77% of respondents endorsed written
consent. In both scenarios, the alternative of general notification received
significantly more support (28.7-37.1%) than the alternative of verbal consent
(12.7-14.0%) (P = 0.001). Forty per cent of respondents preferred and/or
recommended general notification rather than written consent. CONCLUSIONS: The
results suggested that, rather than attempting to waive written consent, current
pRCTs should focus on developing ways to implement written consent that provide
sufficient information without undermining recruitment or increasing selection
bias. The finding that around 40% of respondents endorsed general notification
over written consent raises the possibility that, with educational efforts, the
majority of Spaniards might accept general notification for low-risk pRCTs.
PMID- 28419520
TI - Case with acute urticaria by red meat after Haemaphysalis longicornis bite.
PMID- 28419521
TI - Cytokinetic Abscission: Phosphoinositides and ESCRTs Direct the Final Cut.
AB - Cytokinetic abscission involves the fine and regulated recruitment of membrane
remodeling proteins that participate in the abscission of the intracellular
bridge that connects the two dividing cells. This essential process is mediated
by the concomitant activity of the endosomal sorting complex required for
transport (ESCRT) and the vesicular trafficking directed to the midbody.
Phosphoinositides (PtdIns), produced at plasma membrane, and endosomes, act as
molecular intermediates by recruiting effector proteins involved in multiple
cellular processes, such as intracellular signaling, endo- and exo-cytosis, and
membrane remodeling events. Emerging evidences suggest that PtdIns have an active
role in recruiting key elements that control the stability and the remodeling of
the cytoskeleton from the furrow ingression to the abscission, at the end of
cytokinesis. Accordingly, a possible concomitant and coordinated activity between
PtdIns production and ESCRT machinery assembly could also exist and recent
findings are pointing the attention on poorly understood ESCRT subunits
potentially able to associate with PtdIns rich membranes. Although further
studies are required to link PtdIns to ESCRT machinery during abscission, this
might represent a promising field of study. J. Cell. Biochem. 118: 3561-3568,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419519
TI - Deletion of a Distal RANKL Gene Enhancer Delays Progression of Atherosclerotic
Plaque Calcification in Hypercholesterolemic Mice.
AB - Receptor activator of NF-kappaB ligand (RANKL) is a TNF-like cytokine which
mediates diverse physiological functions including bone remodeling and immune
regulation. RANKL has been identified in atherosclerotic lesions; however, its
role in atherosclerotic plaque development remains elusive. An enhancer located
75 kb upstream of the murine Rankl gene's transcription start site designated D5
is important for its calciotropic hormone- and cytokine-mediated expression.
Here, we determined the impact of RANKL levels in atherosclerotic plaque
development in the D5 enhancer-null (D5-/- ) mice in an atherogenic Apoe-/-
background fed a high-fat diet (HFD). Rankl mRNA transcripts were increased in
aortic arches and thoracic aortae of Apoe-/- mice; however, this increase was
blunted in Apoe-/- ;D5-/- mice. Similarly, higher Rankl transcripts were
identified in splenic T lymphocytes in Apoe-/- mice, and their levels were
reduced in Apoe-/- ;D5-/- mice. When analyzed by micro-computed tomography (uCT),
atherosclerotic plaque calcification was identified in six out of eight Apoe-/-
mice, whereas only one out of eight Apoe-/- ;D5-/- mice developed plaque
calcification after 12 weeks of HFD. However, following 18 weeks of HFD
challenge, all of Apoe-/- and Apoe-/- ;D5-/- animals developed atherosclerotic
plaque calcification. Likewise, atherosclerotic lesion sizes were site
specifically reduced in the aortic arch of Apoe-/- ;D5-/- mice at initial stage
of atherosclerosis and this effect was diminished as atherosclerosis proceeded to
a more advanced stage. Our data suggest that deletion of the RANKL D5 enhancer
delays the progression of atherosclerotic plaque development and plaque
calcification in hypercholesterolemic mice. This work provides important insight
into RANKL's regulatory role in atherosclerosis. J. Cell. Biochem. 118: 4240
4253, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419522
TI - A general empirical model for renal drug handling in pharmacokinetic analyses.
AB - Dose adjustment in renal insufficiency is generally based on the assumption that
renal drug clearance is related linearly to glomerular filtration rate. The
theory underpinning this model is the intact nephron hypothesis, which says that
impaired renal function is caused by a reduction in the number of complete
(intact) nephrons. The purpose of the present commentary is to propose a general
empirical model for renal drug handling. We will explore models for renal
function under two scenarios: one that aligns with the intact nephron hypothesis,
and one that relaxes the assumptions of this hypothesis. We propose that a
nonlinear, non-intact nephron model will allow for differences in renal drug
handling, while incorporating the intact nephron hypothesis model as a special
case.
PMID- 28419523
TI - Multiple imputation to evaluate the impact of an assay change in national
surveys.
AB - National health surveys, such as the National Health and Nutrition Examination
Survey, are used to monitor trends of nutritional biomarkers. These surveys try
to maintain the same biomarker assay over time, but there are a variety of
reasons why the assay may change. In these cases, it is important to evaluate the
potential impact of a change so that any observed fluctuations in concentrations
over time are not confounded by changes in the assay. To this end, a subset of
stored specimens previously analyzed with the old assay is retested using the new
assay. These paired data are used to estimate an adjustment equation, which is
then used to 'adjust' all the old assay results and convert them into
'equivalent' units of the new assay. In this paper, we present a new way of
approaching this problem using modern statistical methods designed for missing
data. Using simulations, we compare the proposed multiple imputation approach
with the adjustment equation approach currently in use. We also compare these
approaches using real National Health and Nutrition Examination Survey data for
25-hydroxyvitamin D. Published 2017. This article is a U.S. Government work and
is in the public domain in the USA.
PMID- 28419524
TI - Fibronectin From Oviductal Cells Fluctuates During the Estrous Cycle and
Contributes to Sperm-Oviduct Interaction in Cattle.
AB - During the passage of sperm through the oviduct, spermatozoa bind to the
oviductal epithelium and form the oviductal reservoir. This interaction keeps the
fertilizing capacity of sperm until ovulation-associated signals induce sperm
release from the oviductal epithelium, allowing the transit of spermatozoa to the
fertilization site. Fibronectin is a glycoprotein from the extracellular matrix
that binds to alpha5beta1 receptors. Fibronectin has been found to be expressed
in the oviduct, whereas alpha5beta1 has been found to be expressed in the sperm
of different species. Fibronectin is involved through alpha5beta1 in sperm
functions. The aim of this work was to study the participation of oviductal
fibronectin in the regulation of the sperm-oviduct interaction in cattle. We
found that oviductal epithelial cells differentially expressed all mRNA splice
variants of fibronectin during the estrous cycle. Fibronectin was localized in
the apical region of oviductal epithelial cells and fibronectin levels in the
oviductal fluid fluctuated during the estrous cycle. Also, bovine spermatozoa
expressed alpha5beta1. Using in vitro sperm-oviduct co-cultures, we found that
spermatozoa were attached to the oviductal epithelium through alpha5beta1. The
incubation of co-cultures with fibronectin induced sperm release from the
oviductal cells through alpha5beta1. The sperm population released from oviductal
cells by fibronectin was enriched in motile and capacitated spermatozoa. Based on
our in vitro culture system results, we propose that fibronectin and alpha5beta1
are involved in the sperm-oviduct interaction. Also, an increase in fibronectin
levels in the oviductal fluid during the pre-ovulatory period may promote sperm
release from the oviductal epithelium in cattle. J. Cell. Biochem. 118: 4095
4108, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419525
TI - Method comparison and generation of plasma biochemistry RIs for the White
rhinoceros on a point-of-care and wet chemistry analyzer.
AB - BACKGROUND: Plasma biochemistry analysis may aid the management of White
rhinoceros with poaching or other injuries. Analyzer- and species-specific RIs
are necessary to evaluate health status and identify abnormalities. OBJECTIVES:
The purpose of the study was to perform a comparison study between the IDEXX
VetTest and Roche Cobas Integra 400 Plus, and to generate analyzer-specific RIs
for White rhinoceros according to published guidelines. METHODS: Comparison was
carried out using White rhinoceros plasma samples from healthy and diseased
animals. Reference intervals for albumin, ALT, AST, CK, creatinine, GGT,
globulins, glucose, phosphorus, total proteins, and urea were determined from a
sample group of chemically immobilized healthy adult White rhinoceros from the
Kruger National Park, South Africa. RESULTS: There was a significant analytic
bias for all analytes between the 2 analyzers. Results for glucose and total
protein were clinically equivalent based on total allowable error limits.
Reference intervals were generated from 51 individuals (26 male, 25 female) for
all analytes except ALT on the VetTest. DISCUSSION: The type, direction, and
magnitude of bias between the VetTest and Cobas appeared to be species- and
analyzer-specific, when compared to other studies. These measures of bias may be
used for comparability testing. Reference intervals for total proteins (VetTest
77-108 g/L, Cobas 77-110 g/L) and globulins (VetTest 47-79 g/L, Cobas 51-87 g/L)
were high compared to other uneven-toed ungulates. CONCLUSION: Plasma samples
from White rhinoceros can be evaluated on both the VetTest and Cobas. Results
from this study will aid conservation efforts directed toward this species.
PMID- 28419526
TI - Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and
Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve
the Survival Rate of Septic Mice.
AB - Sepsis is one of the most challenging health problems worldwide. Our previous
study showed that chronic schistosoma japonica (SJ) infection might increase
serum anti-inflammatory factors to play a protective role, thus improving the
survival rate of septic mice. Further research revealed that SJ infection
promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS
induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-beta1
expression; inhibited TNF-alpha and iNOS expression; and blocked the effect of
LPS-promoted TNF-alpha and iNOS expression. Furthermore, adoptive transfer of ex
vivo programed M2 macrophages significantly increased the survival rate of septic
mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played
the same role as worm infection but had no impact on M1 macrophages. SEA reduced
LPS-induced TNF-alpha and iNOS expression, decreased the inhibitory effect of LPS
on IL-10 and TGF-beta1 expression, increased STAT6 phosphorylation, and up
regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K
inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be
reduced. Therefore, worm infection has a protective effect in septic mice in
which SEA may play a key role via the STAT6 and PI3K pathways. This finding may
provide a favorable solution for the treatment of sepsis, especially early cases.
J. Cell. Biochem. 118: 4230-4239, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419527
TI - The "rectosigmoid brake": Review of an emerging neuromodulation target for
colorectal functional disorders.
AB - The regulation of gastrointestinal motility encompasses several overlapping
mechanisms including highly regulated and coordinated neurohormonal circuits.
Various feedback mechanisms or "brakes" have been proposed. While duodenal,
jejunal, and ileal brakes are well described, a putative distal colonic brake is
less well defined. Despite the high prevalence of colonic motility disorders,
there is little knowledge of colonic motility owing to difficulties with organ
access and technical difficulties in recording detailed motor patterns along its
entire length. The motility of the colon is not under voluntary control. A wide
range of motor patterns is seen, with long intervals of intestinal quiescence
between them. In addition, the use of traditional manometric catheters to record
contractile activity of the colon has been limited by the low number of widely
spaced sensors, which has resulted in the misinterpretation of colonic motor
patterns. The recent advent of high-resolution (HR) manometry is revolutionising
the understanding of gastrointestinal motor patterns. It has now been observed
that the most common motor patterns in the colon are repetitive two to six cycles
per minute (cpm) propagating events in the distal colon. These motor patterns are
prominent soon after a meal, originate most frequently in the rectosigmoid
region, and travel in the retrograde direction. The distal prominence and the
origin of these motor patterns raise the possibility of them serving as a braking
mechanism, or the "rectosigmoid brake," to limit rectal filling. This review aims
to describe what is known about the "rectosigmoid brake," including its
physiological and clinical significance and potential therapeutic applications.
PMID- 28419528
TI - An updated synthesis of [11 C]carfentanil for positron emission tomography (PET)
imaging of the MU-opioid receptor.
AB - [11 C]Carfentanil ([11 C]CFN) is a selective radiotracer for in vivo positron
emission tomography imaging studies of the MU-opioid system that, in our
laboratories, is synthesized by methylation of the corresponding carboxylate
precursor with [11 C]MeOTf, and purified using a C2 solid-phase extraction
cartridge. Changes in the commercial availability of common C2 cartridges have
necessitated future proofing the synthesis of [11 C]CFN to maintain reliable
delivery of the radiotracer for clinical imaging studies. An updated synthesis of
[11 C]CFN is reported that replaces a now obsolete purification cartridge with a
new commercially available version and also substitutes the organic solvents used
in traditional production methods with ethanol.
PMID- 28419529
TI - Critical discourse analysis of social justice in nursing's foundational
documents.
AB - OBJECTIVE: Social inequities threaten the health of the global population. A
superficial acknowledgement of social justice by nursing's foundational documents
may limit the degree to which nurses view injustice as relevant to nursing
practice and education. The purpose was to examine conceptualizations of social
justice and connections to broader contexts in the most recent editions. DESIGN:
Critical discourse analysis examines and uncovers dynamics related to power,
language, and inequality within the American Nurses Association's Code of Ethics,
Scope and Standards of Practice, and Social Policy Statement. RESULTS: This
analysis found ongoing inconsistencies in conceptualizations of social justice.
Although the Code of Ethics integrates concepts related to social justice far
more than the other two, tension between professionalism and social change
emerges. The discourse of professionalism renders interrelated cultural, social,
economic, historical, and political contexts nearly invisible. CONCLUSION:
Greater consistency would provide a clearer path for nurses to mobilize and
engage in the courageous work necessary to address social injustice. These
findings also call for an examination of how nurses can critique and use the
power and privilege of professionalism to amplify the connection between social
institutions and health equity in nursing education, practice, and policy
development.
PMID- 28419530
TI - Differential expression profile analysis of PSTK-regulated mRNAs in podocytes.
AB - This study aimed to elucidate the precise mechanisms underlying the protective
effects of phosphoseryl-tRNA kinase (PSTK) against cisplatin-induced podocyte
injury. PSTK overexpression and knockdown vectors were generated and transfected
into MPC-5. PSTK levels were measured, and transcriptome sequencing was
conducted. Differential expression analysis was performed to identify mRNAs that
were positively and negatively correlated with PSTK. We selected 10 candidate
genes identified via real-time quantitative polymerase chain reaction and Western
blotting for further analysis. As expected, PSTK levels were significantly higher
in PSTK-overexpressing podocytes and significantly lower in PSTK-knockdown
podocytes. PSTK overexpression resulted in the upregulation of 122 genes and
downregulation of 372 genes in podocytes. On the other hand, PSTK knockdown
resulted in the upregulation of 231 genes and downregulation of 445 genes.
Furthermore, the analysis revealed that 11 genes were positively correlated with
PSTK, whereas 20 genes were negatively correlated with PSTK. The obtained PSTK
regulated genes were primarily involved in molecular function, biological
process, and cellular component, as well as the angiogenesis pathway. Wnt family
member 10A levels were significantly higher after PSTK overexpression, but were
significantly lower after PSTK knockdown. In addition, Na(+)/K(+) ATPase subunit
alpha-2 and matrix metalloproteinase 9 levels were significantly downregulated
after PSTK overexpression, but significantly upregulated upon PSTK knockdown.
Cell proliferation was significantly increased upon PSTK overexpression, but
significantly decreased upon PSTK suppression. The results of this study not only
identified several significant PSTK-regulated genes for further validation, but
also provided insights into the mechanisms underlying the protective effects of
PSTK on podocytes. This article is protected by copyright. All rights reserved.
PMID- 28419531
TI - Urinary incontinence and hydration: A population-based analysis.
AB - AIMS: To determine if there is an association between urinary incontinence (UI)
and an objective measure of hydration status in men and women in a nationwide,
population-based sample. METHODS: We utilized data from the 2009 to 2010 and 2011
to 2012 National Health and Nutrition Examination Surveys (NHANES), cross
sectional surveys of the US non-institutionalized population. Our primary outcome
was moderate/severe UI measured using a validated scale. Our exposure of interest
was hydration status. Urine osmolality >= 800 mOsm/kg defined dehydration versus
adequate hydration (<800 mOsm/kg). We included men and women >= 20 years who had
both UI and urine osmolality data. Using multivariable models, we controlled for
age, race/ethnicity, BMI, chronic kidney disease, the interaction of age with
osmolality, and hysterectomy (women only). RESULTS: Among the 11 482 total
subjects, 9497 (83%-4882 men and 4615 women) had both UI and urine osmolality
data. Compared to women, men were less likely to report UI (5.9% vs 18.9%; P <
0.001) and more likely to be dehydrated (33.4% vs 24.0%; P < 0.001). In bivariate
analysis, men and women who were dehydrated had less UI than men with adequate
hydration (men: 3.5% vs 7.6%; P < 0.001; women: 16.3% vs 20.0%; P = 0.02);
however, dehydration was not associated with UI in men (OR 0.2, 95% CI 0.6-1.0)
or in women (OR 0.8, 95% CI 0.4-1.5) in multivariable models. CONCLUSIONS:
Hydration status as defined by urine osmolality was not associated with moderate
to severe urinary incontinence in men or women.
PMID- 28419532
TI - ICS Educational Module: Electromyography in the assessment and therapy of lower
urinary tract dysfunction in adults.
AB - AIM: To present the teaching module "Electromyography in the assessment and
therapy of lower urinary tract dysfunction in adults." This teaching module
embodies a presentation, in combination with this manuscript. This manuscript
serves as a scientific background review; the evidence base made available on ICS
website to summarize current knowledge and recommendations. METHODS: This review
has been prepared by a Working Group of The ICS Urodynamics Committee. The
methodology used included comprehensive literature review, consensus formation by
the members of the Working Group, and review by members of the ICS Urodynamics
Committee core panel. RESULTS: Electromyography (EMG) is a method to record
spontaneous or artificially induced electrical activity of the nerve-muscle unit
or to test nerve conductivity. EMG of the anal sphincter using surface electrode
is most widely used screening technique to detect detrusor-sphincter dyssynergia
in urology. It is non-invasive and easy to perform. EMG methods using needle
electrodes are reserved for diagnostics in well selected group of mainly
neurogenic patients. These methods require expertise in the field of general EMG
and are usually performed by neurologist and neuro-physiologist. The evidence in
many aspects of use of EMG in urology remains sparse. CONCLUSIONS: Currently EMG
methods rarely play a decision making role in selecting proper treatment of lower
urinary tract dysfunction. With the current efforts to improve phenotyping of
these patients in order to provide individualized treatment, the role of EMG
could increase.
PMID- 28419533
TI - A new approach for radiosynoviorthesis: A dose-optimized planning method based on
Monte Carlo simulation and synovial measurement using 3D slicer and MRI.
AB - PURPOSE: Recently, there has been a growing interest in a methodology for dose
planning in radiosynoviorthesis to substitute fixed activity. Clinical practice
based on fixed activity frequently does not embrace radiopharmaceutical dose
optimization in patients. The aim of this paper is to propose and discuss a dose
planning methodology considering the radiological findings of interest obtained
by three-dimensional magnetic resonance imaging combined with Monte Carlo
simulation in radiosynoviorthesis treatment applied to hemophilic arthropathy.
METHOD: The parameters analyzed were: surface area of the synovial membrane
(synovial size), synovial thickness and joint effusion obtained by 3D MRI of nine
knees from nine patients on a SIEMENS AVANTO 1.5 T scanner using a knee coil. The
3D Slicer software performed both the semiautomatic segmentation and quantitation
of these radiological findings. A Lucite phantom 3D MRI validated the
quantitation methodology. The study used Monte Carlo N-Particle eXtended code
version 2.6 for calculating the S-values required to set up the injected activity
to deliver a 100 Gy absorbed dose at a determined synovial thickness. The
radionuclides assessed were: 90Y, 32P, 188Re, 186Re, 153Sm, and 177Lu, and the
present study shows their effective treatment ranges. RESULT: The quantitation
methodology was successfully tested, with an error below 5% for different
materials. S-values calculated could provide data on the activity to be injected
into the joint, considering no extra-articular leakage from joint cavity.
Calculation of effective treatment range could assist with the therapeutic
decision, with an optimized protocol for dose prescription in RSO. CONCLUSION:
Using 3D Slicer software, this study focused on segmentation and quantitation of
radiological features such as joint effusion, synovial size, and thickness, all
obtained by 3D MRI in patients' knees with hemophilic arthropathy. The
combination of synovial size and thickness with the parameters obtained by Monte
Carlo simulation such as effective treatment range and S-value, from which is
calculated the injected activity, could be used for treatment planning in RSO.
Data from this methodology could be a potential aid to clinical decision making
by selecting the most suitable radionuclide; justifying the procedure,
fractioning the dose, and the calculated injected activity for children and
adolescents, considering both the synovial size and thickness.
PMID- 28419534
TI - Endocrine Imbalance Associated With Proteome Changes in Diabetes.
AB - The dynamics of cellular metabolism involves rapid interactions between proteins
and nucleic acids, proteins and proteins, and signaling. These involve the
interactions with respect to the sulfur bond, noncovalent electrostatic
interactions, protein structure stabilization and protein-ligand binding, weak
electrostatic interactions in proteins, oxygen radicals that initiate a change in
conformation and a chain of events. We review a development in molecular medicine
that is a very promising work in progress. We also review the current and future
research methods involving mitochondria. Long-term effects of diabetes include
glycation of proteins, for example, glycohemoglobin (HbA1c), increased risk of
cardiovascular diseases, atherosclerosis, retinopathy, nephropathy, and
neurological dysfunctions. Tissues are exposed to significant quantities of
highly reactive chemical species including nitric oxide * NO and reactive oxygen
species ROS over months to years, to an extent generated by mitochondrial
activities. The reactions of * NO can be broadly discussed with reference to
three main processes which control their fate in biological systems: (1)
diffusion and intra-cellular consumption; (2) autooxidation to form nitrous
anhydride N2 O3 ; and (3) reaction with superoxide O2* - to form peroxynitrite
ONOO-. Reactive nitrogen species produced by macrophages and neutrophils in the
interstitial space, with emphasis on * NO, N2 O3 , ONOO-, and nitrogen dioxide
radicals * NO2 generate protein and DNA damage. Serum thiol (-SH) groups act as
an important extracellular scavenger of peroxides and are therefore helpful in
protecting the surrounding tissues. The events described here are a homeostatic
endocrine imbalance that is associated with proteostasis. The advances we have
seen in untangling this web of interactions are sure to continue at a
breathtaking pace. J. Cell. Biochem. 118: 3569-3576, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28419535
TI - Enhanced Entrapment and Improved in Vitro Controlled Release of N-Acetyl Cysteine
in Hybrid PLGA/Lecithin Nanoparticles Prepared Using a Nanoprecipitation/Self
Assembly Method.
AB - To enhance the in vitro controlled release of N-acetyl cysteine (NAC), hybrid
nanoparticles (NPs) consisting of a poly(lactide-co-glycolide) (PLGA) hydrophobic
core and a soybean lecithin mono-layer coat were prepared. Hybrid NPs were
synthesized using a nanoprecipitation combined with self-assembly method. To
characterize prepared NPs, zeta potential, diameter size, surface morphology,
disparity, and lipid coating of hybrid NPs were detrmined using dynamic light
scattering, scanning electron microscope and Fourier transform infrared
spectroscopy techniques. High-performance liquid chromatography was employed to
evaluate drug loading yield and encapsulation efficiency and in vitro drug
release of prepared NPs. The cytotoxicity of hybrid NPs was assayed on normal
L929 alveolar epithelial cells using MTT method. Prepared NPs were found to
disperse as individual NPs with a well-defined spherical shape. The hydrodynamic
diameter and surface charge of NAC-loaded hybrid NPs were 81.8 +/- 1.3 nm and
33.1 +/- 2.1 mV, respectively. Drug loading yield and encapsulation efficiency of
NAC-loaded hybrid NPs were found to be 38 +/- 2.1% and 67 +/- 5.7%, respectively.
Prepared hybrid NPs showed no significant cytotoxicity against normal alveolar
cells. Our data suggest that the hybrid PLGA-lecithin NPs may be An efficient
controlled release drug delivery system for NAC. J. Cell. Biochem. 118: 4203
4209, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419536
TI - Characteristics and related factors of Japanese mothers who have faced
difficulties with childrearing.
AB - OBJECTIVE: To identify characteristics of mothers who face difficulties with
childrearing. DESIGN AND SAMPLE: Cross-sectional study. During 2014, 221 mothers
and 248 children living in City A within the Tokyo metropolis were registered as
requiring help with childrearing. Nursing records of 205 mothers (92.8%) and
their 227 children (91.5%) were available. We excluded 29 mothers and children
owing to incomplete data for a final sample of 176 mothers (79.6%) and 198
children (79.8%). MEASURES: Difficulties with childrearing were assessed by self
reported questionnaires at the newborn child's 4-month health checkups. Data on
maternal and child variables were collected from nursing records. RESULTS: The
"Difficulties group" included 59 mothers (35.4%) and their 70 children. Logistic
regression analysis showed that mothers who were aged 40 years or older, who had
a total score on the Edinburgh Postnatal Depression Scale of 9 or greater, who
used more child-care support services, and who were monitored more frequently by
public health nurses had a high risk of facing difficulties with childrearing.
CONCLUSIONS: Periodic monitoring by PHNs is a key strategy to improve the impact
of the difficulties of childrearing for mothers of yoshien jido and their
children.
PMID- 28419537
TI - Electromagnetic tracking for femoral derotation osteotomy-an in vivo study.
AB - Femoral derotation osteotomy delivers good to excellent results in the treatment
of rotational gait abnormalities and especially in internal rotation gait. The
outcome of the procedure has been evaluated in numerous short- and long-term
studies. Although reasons for recurrence and over-/under-correction have been
unveiled in earlier studies the mechanisms are still not fully understood. False
intra-operative assessment of the derotation angle may contribute to imprecise
outcomes. In a recent saw-bone study we evaluated an electromagnetic tracking
system in comparison to conventional goniometer measurement and a CT reference
measurement and found it to be extremely accurate, whereas the use of a
conventional goniometer for derotation measurement showed a high inter- and intra
rater variability. The current study evaluates the electromagnetic tracking
system for continuous intra-operative derotation control under real OR
conditions. Adults (age: 18-40 years) with the diagnosis of internal rotation
gait, independent of the underling pathology, undergoing a supracondylar
deroation osteotomy were included. A rotational CT scan was conducted before and
in close proximity after surgery and the difference served as reference for the
electromagnetic tracking results. The results showed a mean deviation of 2.6
degrees (1.2-5.5 degrees ) in comparison to the reference measurement of the pre
and post-operative CT scans. The system proved to be stable under OR conditions
with a good usability and a small technical footprint. Electromagnetic tracking
delivers a precise, reliable, and independent assessment of intra-operative
derotation angles in femoral derotation osteotomies. (c) 2017 Orthopaedic
Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2652-2657,
2017.
PMID- 28419538
TI - Receiving early information and trusting Swedish child health centre nurses
increased parents' willingness to vaccinate against rotavirus infections.
AB - AIM: Rotavirus vaccines are effective against severe infections, but have a
modest impact on mortality in high-income countries. Parental knowledge and
attitudes towards vaccines are crucial for high vaccination coverage. This study
aimed to identify why parents refused to let their infant have the vaccination or
were unsure. METHODS: This cross-sectional study was based on 1,063
questionnaires completed by the parents of newborn children in 2014. Stepwise
logistic regression was used to identify the main predictors. RESULTS: Most (81%)
parents intended to vaccinate their child against the rotavirus, while 19% were
unwilling or uncertain. Parents with less education and children up to five weeks
of age were more likely to be unwilling or uncertain about vaccinating their
child. Factors associated with a refusal or uncertainty about vaccinating were
not having enough information about the vaccine, no intention of accepting other
vaccines, paying little heed to the child health nurses' recommendations,
thinking that the rotavirus was not a serious illness and not believing that the
vaccine provided protection against serious forms of gastroenteritis. CONCLUSION:
Early information, extra information for parents with less education and close
positive relationships between parents and child health nurses were important
factors in high rotavirus vaccination rates.
PMID- 28419539
TI - PD-L1 expression in extrahepatic cholangiocarcinoma.
AB - AIMS: To investigate the expression of the programmed cell death 1 (PD-1)
receptor-programmed cell death ligand 1 (PD-L1) pathway and the
clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA).
METHODS AND RESULTS: Tissue samples from patients with eCCA [n = 69; perihilar
cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical
resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and
CD163 expression, and correlations with clinicopathological characteristics,
including survival data, were determined. PD-L1 was found on both tumour cells of
eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant
correlations of PD-L1 expression on cancer cells with venous invasion (P = 0.031)
and poor differentiation of the tumour (P = 0.048) were observed. In 19 of 69
(27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas
infiltration with CD3-positive and CD163-positive cells was found in 63 of 69
(91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five
CD3-positive cells per high-power field was significantly correlated with poorer
differentiation (P = 0.015) and venous invasion (P < 0.001) of CCA. PD-L1
expression was not correlated with patient survival, but PD-L1 expression on
tumour cells combined with low infiltration of CD3-positive TILs was associated
with an unfavourable outcome (P = 0.027). CONCLUSION: Only a small number of eCCA
patients are PD-L1-positive, which might be important for future application of
PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup
of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more
invasive growth and worse overall survival.
PMID- 28419540
TI - Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager.
AB - We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed
cysts. Reactive inflammation and sterile purulent drainage may be an
underrecognized feature of DGA.
PMID- 28419541
TI - When should active surveillance for prostate cancer stop if no progression is
detected?
AB - BACKGROUND: A significant proportion of screen-detected men with prostate cancer
may be overdiagnosed. Active Surveillance (AS) has emerged as a way to mitigate
this problem, by delaying treatment of men, who are at low-risk until this
becomes necessary. However, it is not known after how much time or biopsy rounds
should patients stop AS and transition to conservative management (CM), if no
progression is detected. METHODS: We used a microsimulation model with natural
history of prostate cancer based on ERSPC and SEER data. We modeled referral to
treatment while in AS, based on Johns Hopkins treatment-free survival data. We
projected lifetime costs and effects of AS (and radical treatment, if progression
is detected) under different biopsy follow-up schedules compared to CM, where
radical treatment only occurs when men would be clinically diagnosed in absence
of screening. RESULTS: For men with low-risk disease in younger age groups (55
65), AS is cost-effective for up to 7 yearly biopsy rounds. For men older than
65, even one biopsy round results in quality adjusted life years (QALYs) lost,
though it may result in QALYs gained for men without previous screening. For men
with intermediate-risk disease AS is cost-effective even for men in 65-75 age
group. CONCLUSIONS: The benefit of AS when compared to CM is strongly dependent
on life expectancy and disease risk. Clinicians should take this into account
when selecting men to AS, deciding on biopsy frequency and when to stop AS
surveillance rounds and transition to CM.
PMID- 28419542
TI - Effect of nanosilver on metabolism in rainbow trout (Oncorhynchus mykiss): An
investigation using different respirometric approaches.
AB - Nanosilver (nAg) has been incorporated into many consumer products, including
clothing and washing machines, because of its antimicrobial properties.
Consequently, the potential for its release into aquatic environments is of
significant concern. Documented toxic effects on fish include altered gene
expression, gill damage, and impaired gas exchange, as well as mortality at high
nAg concentrations. The present study reports the effects of nAg on the
metabolism of rainbow trout (Oncorhynchus mykiss). Fish were exposed to
environmentally relevant concentrations (0.28 +/- 0.02 MUg/L) and higher (47.60
+/- 5.13 MUg/L) for 28 d, after which their standard metabolic rate (SMR), forced
maximum metabolic rate (MMRf ), and spontaneous maximum metabolic rate (MMRs )
were measured. There was no effect observed in SMR, MMRf , or MMRs , suggesting
that nAg is unlikely to directly affect fish metabolism. On average, MMRs tended
to be greater than MMRf , and most MMRs occurred when room lighting increased.
The timing of MMRf chase protocols was found to affect both MMRf and SMR
estimates, in that chasing fish before respirometric experiments caused higher
MMRf estimates and lower SMR estimates. Although compounded effects involving nAg
and other environmental stressors remain unknown, the present study indicates
that the tested range of nAg is unlikely to constrain fish metabolism. Environ
Toxicol Chem 2017;36:2722-2729. (c) 2017 SETAC.
PMID- 28419543
TI - Aging does not alter tendon mechanical properties during homeostasis, but does
impair flexor tendon healing.
AB - Aging is an important factor in disrupted homeostasis of many tissues. While an
increased incidence of tendinopathy and tendon rupture are observed with aging,
it is unclear whether this is due to progressive changes in tendon cell function
and mechanics over time, or an impaired repair reaction from aged tendons in
response to insult or injury. In the present study, we examined changes in the
mechanical properties of Flexor Digitorum Longus (FDL), Flexor Carpi Ulnaris
(FCU), and tail fascicles in both male and female C57Bl/6 mice between 3 and 27
months of age to better understand the effects of sex and age on tendon
homeostasis. No change in max load at failure was observed in any group over the
course of aging, although there were significant decreases in toe and linear
stiffness in female mice from 3 to 15 months, and 3 to 27 months. No changes in
cell proliferation were observed with aging, although an observable decrease in
cellularity occurred in 31-month old tendons. Given that aging did not
dramatically alter tendon mechanical homeostasis we hypothesized that a
disruption in tendon homeostasis, via acute injury would result in an impaired
healing response. Significant decreases in max load, stiffness, and yield load
were observed in repairs of 22-month old mice, relative to 4-month old mice. No
changes in cell proliferation were observed between young and aged, however, a
dramatic loss of bridging collagen extracellular matrix was observed in aged
repairs suggest that matrix production, but not cell proliferation leads to
impaired tendon healing with aging. Results (c) 2017 Orthopaedic Research
Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2716-2724, 2017.
PMID- 28419544
TI - Adults born preterm: a review of general health and system-specific outcomes.
AB - : In this review of 126 publications, we report that an overwhelming majority of
adults born at preterm gestations remain healthy and well. However, a small, but
a significant fraction of them remain at higher risk for neurological,
personality and behavioural abnormalities, cardio-pulmonary functional
limitations, systemic hypertension and metabolic syndrome compared to their term
born counterparts. The magnitude of increased risk differed across organ systems
and varied across reports. The risks were proportional to the degree of
prematurity at birth and seemed to occur more frequently among preterm infants
born in the final two decades of the 20th century and later. These findings have
considerable public health and clinical practice relevance. CONCLUSION: Preterm
birth needs to be considered a chronic condition, with a slight increase in the
risk for long-term morbidities among adults born preterm. Therefore, obtaining a
history of gestational age and weight at birth should be a routine part of care
for patients of all age groups.
PMID- 28419545
TI - Intermolecular Interactions Between DMalpha and DMbeta Proteins in BuLA-DM
Complex of Water Buffalo Bubalus bubalis.
AB - The major histocompatibility complex (MHC) with its three classes represents a
cluster of tightly linked genes with defined immunological and non-immunological
functions. The DM, a MHC class II molecule is formed by the non-covalent
association of DMalpha and DMbeta chains. It binds with the processed peptide
antigens and presents them to T lymphocytes, thereby triggering the immune
responses. Startlingly, the expression pattern and structural organization of
DMalpha and DMbeta proteins in buffalo remains undefined. We isolated and
purified the DMalpha and DMbeta proteins from Bubalus bubalis using gel
filtration chromatography. Employing western blotting and immunohistochemistry,
highest expression of these proteins was observed in spleen and were later
localized in the cytoplasm. We modelled 3D structures of the proteins and
assessed the binding interface of BuLA-DM docked complex. In the process, we
uncovered 9 DMalpha and 8 DMbeta specific residues participating in the formation
of BuLA-DM complex. Our work demonstrated active participation of the critical
amino acid residues engaged in the formation of BuLA-DM complex facilitating
deeper understanding on the structure-function relationship of these proteins. J.
Cell. Biochem. 118: 4254-4266, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419546
TI - Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal
Development, and Osteoblast and Osteoclast Function.
AB - The coupling of osteoblasts and osteocytes by connexin43 (Cx43) gap junctions
permits the sharing of second messengers that coordinate bone cell function and
cortical bone acquisition. However, details of how Cx43 converts shared second
messengers into signals that converge onto essential osteogenic processes are
incomplete. Here, we use in vitro and in vivo methods to show that Cx43 and Runx2
functionally interact to regulate osteoblast gene expression and proliferation,
ultimately affecting cortical bone properties. Using compound hemizygous mice for
the Gja1 (Cx43) and Runx2 genes, we observed a skeletal phenotype not visible in
wild-type or singly hemizygous animals. Cortical bone analysis by micro-computed
tomography (MUCT) revealed that 8-week-old male, compound Gja1+/- Runx2+/- mice
have a marked increase in cross-sectional area, endosteal and periosteal bone
perimeter, and an increase in porosity compared to controls. These compound
Gja1+/- Runx2+/- mice closely approximate the cortical bone phenotypes seen in
osteoblast-specific Gja1-conditional knockout models. Furthermore, MUCT analysis
of skulls revealed an altered interparietal bone geometry in compound
hemizygotes. Consistent with this finding, Alizarin red/Alcian blue staining of 2
day-old Gja1+/- Runx2+/- neonates showed a hypomorphic interparietal bone, an
exacerbation of the open fontanelles, and a further reduction in the hypoplastic
clavicles compared to Runx2+/- neonates. Expression of osteoblast genes,
including osteocalcin, osterix, periostin, and Hsp47, was markedly reduced in
tibial RNA extracts from compound hemizygous mice, and osteoblasts from compound
hemizygous mice exhibited increased proliferative capacity. Further, the reduced
osteocalcin expression and hyperproliferative nature of osteoblasts from Cx43
deficient mice was rescued by Runx2 expression. In summary, these findings
provide evidence that Cx43 and Runx2 functionally intersect in vivo to regulate
cortical bone properties and affect osteoblast differentiation and proliferation,
and likely contributes to aspects of the skeletal phenotype of Cx43 conditional
knockout mice. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28419549
TI - Erratum.
PMID- 28419547
TI - Perinatal DNA Methylation at CDKN2A Is Associated With Offspring Bone Mass:
Findings From the Southampton Women's Survey.
AB - Poor intrauterine and childhood growth has been linked with the risk of
osteoporosis in later life, a relationship that may in part be mediated through
altered epigenetic regulation of genes. We previously identified a region within
the promoter of the long non-coding RNA ANRIL encoded by the CDKN2A locus, at
which differential DNA methylation at birth showed correlations with offspring
adiposity. Given the common lineage of adipocytes and osteoblasts, we
investigated the relationship between perinatal CDKN2A methylation and bone mass
at ages 4 and 6 years. Using sodium bisulfite pyrosequencing, we measured the
methylation status of the 9 CpGs within this region in umbilical cord samples
from discovery (n = 332) and replication (n = 337) cohorts of children from the
Southampton Women's Survey, whose bone mass was assessed by dual-energy X-ray
absorptiomietry (DXA; Hologic Discovery). Inverse associations were found between
perinatal CDKN2A methylation and whole-body minus head bone area (BA), bone
mineral content (BMC), and areal bone mineral density (BMD). This was confirmed
in replication and combined data sets (all p < 0.01), with each 10% increase in
methylation being associated with a decrease in BMC of 4 to 9 g at age 4 years (p
<= 0.001). Relationships were similar with 6-year bone mass. Functional
investigation of the differentially methylated region in the SaOS-2 osteosarcoma
cell line showed that transcription factors bound to the identified CpGs in a
methylation-specific manner and that CpG mutagenesis modulated ANRIL expression.
In conclusion, perinatal methylation at CDKN2A is associated with childhood bone
development and has significance for cell function. (c) 2017 American Society for
Bone and Mineral Research.
PMID- 28419548
TI - Detection of prostate cancer-specific transcripts in extracellular vesicles
isolated from post-DRE urine.
AB - BACKGROUND: The measurement of gene expression in post-digital rectal examination
(DRE) urine specimens provides a non-invasive method to determine a patient's
risk of prostate cancer. Many currently available assays use whole urine or cell
pellets for the analysis of prostate cancer-associated genes, although the use of
extracellular vesicles (EVs) has also recently been of interest. We investigated
the expression of prostate-, kidney-, and bladder-specific transcripts and known
prostate cancer biomarkers in urine EVs. METHODS: Cell pellets and EVs were
recovered from post-DRE urine specimens, with the total RNA yield and quality
determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated
transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. RESULTS:
RNA was more consistently recovered from the urine EV specimens, with over 80% of
the patients demonstrating higher RNA yields in the EV fraction as compared to
urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher
than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE
urine EVs indicated that prostate-specific transcripts were more abundant than
kidney- or bladder-specific transcripts. Additionally, patients with prostate
cancer had significantly higher levels of the prostate cancer-associated genes
PCA3 and ERG. CONCLUSIONS: Post-DRE urine EVs are a viable source of prostate
derived RNAs for biomarker discovery and prostate cancer status can be
distinguished from analysis of these specimens. Continued analysis of urine EVs
offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer
detection.
PMID- 28419550
TI - Urban primate ranging patterns: GPS-collar deployments for Macaca fascicularis
and M. sylvanus.
AB - The global increase in urbanization is leading to heavier interface between
humans and wildlife. Within these anthropogenic landscapes, little is known about
ranging patterns, particularly with regard to urban primates. Here we present the
results of the first long-term deployment of multiple GPS collars on two species
of macaques to investigate the impacts of urbanization on urban primate ranging
patterns in Singapore and Gibraltar. Collars data acquisition were excellent with
respect to the amount, quality, and accuracy of data collected; however, remote
connectivity and drop-off functionality was poor across all deployments. Analyses
highlighted high variability in ranging patterns between individuals within each
species that aligned with access to human food resources and patterns of tourism.
Individuals from troops with less access to human food had much larger home,
core, and day ranges relative to those with regular provisioning or raiding
opportunities. Almost no temporal range overlap was observed between any focal
individuals at either site and spatial overlap was low for all but two troops at
each site. We found no relationship between anthropogenic schedules and changes
in ranging patterns. Significant seasonal variation existed for daily path length
and day range size for both the Singapore long-tailed and the Gibraltar Barbary
macaques, with long-tailed macaques increasing their range during the equatorial
monsoon season and Barbary macaques increasing their range during drier, summer
months. This study highlights how the behavioral plasticity found within the
genus Macaca is reflected in ranging pattern variability within urban
environments.
PMID- 28419551
TI - Two-stage test of means of unordered pairs.
AB - The problem of testing equality of means of a bivariate normal distribution on
the basis of a sample of size n has been considered when the labels of the
observations are either missing or not known. The problem may arise in many
applied settings, especially in genetics. Classical likelihood ratio test fails
here because of identifiability problems. We propose a two-stage testing
procedure using a recently developed test in the context of penalized splines.
The proposed testing procedure is found to outperform the tests proposed in the
literature. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419552
TI - Feasibility and utility of portable ultrasound during retrieval of sick preterm
infants.
AB - AIM: Document the incidence of haemodynamic pathology in critically ill preterm
newborns requiring transport. METHOD: A transport neonatologist performed cardiac
and cerebral ultrasound before and after transportation of infants born <=30
weeks gestation. RESULTS: Forty-four newborns were studied in 2008-2015; of them,
21 were transported by road, 19, by helicopter and four, by fixed wing: median
birthweight, 1130 g (680-1960 g) and median gestation, 27 weeks (23-30); 30 of 44
were male babies. Antenatal steroid course was complete in two babies. Ultrasound
in the referring hospital was at a mean of two hours: 47 minutes (00:15-7:00) of
age. Low systemic blood flow was common: 50% had right ventricular output
<150mL/kg/min and 23%, a superior vena cava flow <50mL/kg/min. at stabilisation.
Cranial US: 10 Grade I IVH, 2 Grade II IVH, 1 Grade IV IVH and 32 normal scans
pretransport. After transport, three further Grade I IVH were reported. Mortality
was higher in the babies with low systemic blood flow: 4 of 12 (33%) died vs 1 of
31 (6%) in the normal flow group (OR = 7.2, 95% CI: 1.1 to 47, p = 0.022).
CONCLUSION: Point-of-care ultrasound during the retrieval of preterm infants
confirms a high incidence of haemodynamic pathology. The use of ultrasound during
transport may provide an opportunity for earlier targeted circulatory support.
PMID- 28419553
TI - Eight-year follow-up after vascularized fibular epiphyseal transfer for hip
reconstruction.
PMID- 28419554
TI - The major miR-31 target genes STK40 and LATS2 and their implications in the
regulation of keratinocyte growth and hair differentiation.
AB - Emerging evidence indicates that even subtle changes in the expression of key
genes of signalling pathways can have profound effects. MicroRNAs (miRNAs) are
masters of subtlety and generally have only mild effects on their target genes.
The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions
associated with activated keratinocytes, such as the hyperproliferative diseases
psoriasis, non-melanoma skin cancer and hair follicle growth. miR-31 is a marker
of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the
function of keratinocytes. This leads to aberrant proliferation, apoptosis, and
differentiation that results in altered hair growth, while the loss of miR-31
leads to increased hair growth. Through in vitro and in vivo studies, we have
defined a set of conserved miR-31 target genes, including LATS2 and STK40, which
serve as new players in the regulation of keratinocyte growth and hair follicle
biology. LATS2 can regulate growth of keratinocytes and we have identified a
function of STK40 that can promote the expression of key hair follicle programme
regulators such as HR, DLX3 and HOXC13.
PMID- 28419555
TI - Antenatal betamethasone for women at risk for late preterm delivery reduces the
rate of neonatal respiratory complications.
PMID- 28419556
TI - Does motor cortex plasticity depend on the type of mutation in the leucine-rich
repeat kinase 2 gene?
PMID- 28419557
TI - Usefulness of the Valsalva maneuver without a mouthpiece to observe the
hypopharynx using transoral endoscopy.
PMID- 28419558
TI - Age but not Philadelphia positivity impairs outcome in older/elderly patients
with acute lymphoblastic leukemia in Sweden.
AB - OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are
poorly represented in clinical trials. METHODS: Using Swedish national leukemia
registries, we investigated disease/patient characteristics, treatment choices,
outcome, and the impact of an age-adapted protocol (introduced in 2009) in this
population-based study of patients aged 55-85 years, diagnosed with ALL 2005
2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia
(excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred
in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive
protocols, and 20% with a palliative approach. Higher age and WHO performance
status >=2 influenced the choice of palliation. Intensive, palliative, and both
approaches resulted in complete remission rate 83/16/70% and 3-year overall
survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With
intensive treatment, platelet count <=35*109 /L and age >=75 years were adverse
prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor
in the 55-64 year age-group. CONCLUSIONS: We report a high frequency of Ph+ in
older/elderly patients, with no evidence of poorer outcome compared to Ph
negative disease. Overall prognosis for elderly patients with ALL remains dismal,
despite the use of age-adapted treatment.
PMID- 28419559
TI - Impact of the global burden of periodontal diseases on health, nutrition and
wellbeing of mankind: A call for global action.
AB - BACKGROUND: The global burden of periodontal diseases remains high. Population
growth trends, changes in risk factors and improved tooth retention will increase
the socio-economic burden of periodontitis that is responsible for 3.5 million
years lived with disability, 54 billion USD/year in lost productivity and a major
portion of the 442 billion USD/year cost for oral diseases. METHODS: In the
context of the Milan World Exhibition 2015 "Feeding the Planet, Energy for Life,"
a green paper was developed and offered for global consultation by the European
Federation of Periodontology. The final draft was endorsed by professional
organizations around the world and is presented to stakeholders as a call for
global action. RESULTS: Specific actions for the public, policymakers, educators
and professional organizations have been identified in the areas of prevention,
detection and care. These actions align public interest and knowledge, need for
self-care, professional intervention and policies to the best scientific evidence
to proactively promote periodontal health and effectively manage the global
burden of periodontal diseases, in accordance with WHO/UN priorities and
strategies for tackling common non-communicable diseases via the Common Risk
Factor Approach. CONCLUSIONS: A strong and coherent body of evidence allows
identification of actionable preventive, diagnostic and therapeutic strategies to
effectively promote periodontal health and general wellbeing, and better manage
the socio-economic consequences. Action requires consideration of the specific
national scenarios.
PMID- 28419560
TI - Fibroblast Growth Factor-23 Concentration in Dogs with Chronic Kidney Disease.
AB - BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia,
decreased vitamin D metabolite concentrations, and hyperparathyroidism. This
syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been
shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is
an early biomarker of CKD in people. It is an independent risk factor for both
progression of renal disease and survival time in humans and cats with CKD.
Information about FGF-23 in healthy dogs and those with CKD is lacking.
OBJECTIVES: To measure FGF-23 concentration in dogs with different stages of CKD
and determine its association with factors involved in CKD-MBD, including serum
phosphorus and parathyroid hormone (PTH) concentrations. A secondary aim was to
validate an ELISA for measurement of plasma FGF-23 concentration in dogs.
ANIMALS: Thirty-two client-owned dogs with naturally occurring CKD and 10 healthy
control dogs. METHODS: Prospective cross-sectional study. An FGF-23 ELISA was
used to measure plasma FGF-23 concentration in dogs and their association with
serum creatinine, phosphorus, calcium, and PTH concentrations. RESULTS: Plasma
FGF-23 concentrations increased with severity of CKD and were significantly
different between IRIS stages 1 and 2 versus stages 3 and 4 (P < .0001).
Increases in FGF-23 concentrations were more frequent than hyperparathyroidism or
hyperphosphatemia in this cohort. Serum creatinine and phosphorus concentrations
were the strongest independent predictors of FGF-23 concentration. CONCLUSIONS
AND CLINICAL IMPORTANCE: Plasma FGF-23 concentrations increase in dogs with CKD
as disease progresses. Plasma FGF-23 concentrations appear to be useful for
further study of the pathophysiology of CKD-MBD in dogs.
PMID- 28419561
TI - A transition from using multi-step procedures to a fully integrated system for
performing extracorporeal photopheresis: A comparison of costs and efficiencies.
AB - INTRODUCTION: The Pitie Salpetriere Hospital Hemobiotherapy Department, Paris,
France, has been providing extracorporeal photopheresis (ECP) since November
2011, and started using the Therakos(r) CELLEX(r) fully integrated system in
2012. This report summarizes our single-center experience of transitioning from
the use of multi-step ECP procedures to the fully integrated ECP system,
considering the capacity and cost implications. MATERIALS AND METHODS: The total
number of ECP procedures performed 2011-2015 was derived from department records.
The time taken to complete a single ECP treatment using a multi-step technique
and the fully integrated system at our department was assessed. Resource costs
(2014?) were obtained for materials and calculated for personnel time required.
Time-driven activity-based costing methods were applied to provide a cost
comparison. RESULTS: The number of ECP treatments per year increased from 225
(2012) to 727 (2015). The single multi-step procedure took 270 min compared to
120 min for the fully integrated system. The total calculated per-session cost of
performing ECP using the multi-step procedure was greater than with the CELLEX(r)
system (?1,429.37 and ?1,264.70 per treatment, respectively). CONCLUSIONS: For
hospitals considering a transition from multi-step procedures to fully integrated
methods for ECP where cost may be a barrier, time-driven activity-based costing
should be utilized to gain a more comprehensive understanding the full benefit
that such a transition offers. The example from our department confirmed that
there were not just cost and time savings, but that the time efficiencies gained
with CELLEX(r) allow for more patient treatments per year.
PMID- 28419562
TI - International opinions and national surveillance suggest insufficient consensus
regarding the recognition and management practices of infants with congenital
cytomegalovirus infections.
AB - AIM: This study evaluated the recognition and management practices with regard to
congenital cytomegalovirus (cCMV) infections by a select group of experts and
through a national surveillance study. METHOD: A questionnaire was sent to
international experts involved in mother and infant care in 2014-2015. Monthly
surveillance was conducted among Dutch paediatricians for cases of cCMV
infections from 2013 until 2015. RESULTS: The questionnaire was completed by
63/103 (62%) respondents, who indicated that recognition and management practices
varied. Maternal screening was performed by 17/63 (27%) and infant screening by
3/61 (5%) of the respondents. Infant CMV diagnostics were most frequently
initiated due to hepatosplenomegaly and/or an increase in liver transaminases.
Management practices included cranial ultrasound (57/63, 91%) and audiological
follow-up in symptomatic (61/63, 97%) and asymptomatic (52/63, 83%) infants. In
terms of antiviral treatment, 46/63 (73%) treated symptomatic infants only and
6/63 (9%) treated all infected infants. In total, 48 cases were registered
through the Dutch surveillance study and 43/48 (90%) infants were symptomatic.
CONCLUSION: This study indicates that infants with cCMV infection were
insufficiently recognised and highlights the need for consensus on management
practices. Screening of infants and the development of an international
management guideline are recommended.
PMID- 28419563
TI - Whole exome sequencing identified a novel single base pair insertion mutation in
the EYS gene in a six generation family with retinitis pigmentosa.
AB - Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies
(RD) and is characterized by photoreceptor degeneration. RP is clinically and
genetically heterogeneous disorder. More than 70 genes are known and, thus,
identification of causative genes and mutations in known genes is challenging.
This study was designed to identify the underlying genetic defect in a large
extended Saudi family with multiple RP affected members. Fundus photography,
Optical Coherence Tomography (OCT) and visual field perimetry were performed for
affected individuals. Whole exome sequencing was used to detect the underlying
genetic defect in a large family with 12 affected individuals showing autosomal
recessive isolated RP. WES data analysis identified a novel insertion mutation in
the EYS (eyes shut homolog) gene (c.910_911insT; p.Trp304LeufsTer8). Sanger
sequencing validates the variant discovered through exome in all 12 affected
individuals and showed that this mutation is segregating with RP phenotype in an
autosomal recessive manner in 51 individuals of the family tested here. Our study
expands the mutation spectrum of EYS gene in RP patients and extends the body of
evidence that supports the importance of EYS gene in eye development.
PMID- 28419564
TI - Does single mega-dose vitamin A in early neonatal period reduce mortality during
infancy in low- and middle-income countries?
PMID- 28419565
TI - Evolution of silent myocardial ischaemia prevalence and cardiovascular disease
risk factor management in Type 2 diabetes over a 10-year period: an observational
study.
AB - AIMS: To assess the evolution of silent myocardial ischaemia prevalence and of
cardiovascular disease risk factor management over 10 years in people with Type 2
diabetes. METHODS: This repeated cross-sectional study prospectively included 770
people with Type 2 diabetes who presented at our centre in the period 1999-2009.
All had at least one additional cardiovascular disease risk factor, no history of
coronary disease and were screened for silent myocardial ischaemia using
myocardial perfusion imaging. The prevalence of silent myocardial ischaemia,
clinical and biological variables and treatments were collected and compared
among participants screened in three periods: 1999 to 2002; 2003 to 2005; and
2006 to 2009. We also identified predictive factors for silent myocardial
ischaemia. RESULTS: Participants had a mean +/- sd age of 62.3 +/- 9.3 years,
57.4% were men and the mean time from diagnosis of diabetes was 13.4 +/- 9.3
years. Overall, silent myocardial ischaemia screening was positive in 13.9% of
participants. This prevalence decreased sharply over the 10-year study period
(22.6% in 1999-2002, 13.7% in 2003-2005 and 5.9% in 2006-2009; P<0.0001). In
parallel, diastolic and systolic blood pressure, HbA1c and LDL cholesterol
significantly decreased and glitazone and statin use increased (all P<0.001).
Male gender, peripheral artery disease, diastolic blood pressure >80 mmHg and LDL
cholesterol >2.6 mmol/l were independently associated with silent myocardial
ischaemia. Further adjustment showed the screening period had a significant
effect, which erased the effects of diastolic blood pressure and LDL cholesterol.
CONCLUSIONS: The prevalence of silent myocardial ischaemia decreased sharply over
time, and control of the main cardiovascular disease risk factors improved.
Although the causality link cannot be established, the present study supports
current recommendations advocating glycaemic control and intensive management of
cardiovascular factors instead of systematic screening.
PMID- 28419566
TI - Perirhinal accumulation of neuronal alpha-synuclein in a multiple system atrophy
patient with dementia.
AB - We report the case of a 79-year-old Japanese woman who developed cerebellar
ataxia followed by rigidity, dysautonomia and cognitive disorders, and was thus
clinically diagnosed as having possible MSA with dementia. Neuropathological
findings demonstrated not only olivopontocerebellar and striatonigral
degeneration with frequent glial cytoplasmic inclusions (GCIs), but also
degenerative changes in the parahippocampal region, accentuated in the anterior
portion of perirhinal cortex, where neuronal cytoplasmic inclusions (NCIs) and
NFTs were numerous while GCIs were limited. NCIs were frequent in the deep layer,
whereas NFTs were more frequent in superficial cortical layers. Other hippocampal
subregions including subiculum, dentate fascia and cornu ammonis were minimally
involved. NCIs in the perirhinal cortex showed intense argyrophilia with the
Campbell-Switzer silver impregnation method, but not argyrophilic with the
Gallyas method. Most neuronal alpha-synuclein aggregates in dendrosomatic
fraction formed globular/tadpole-like, and ultrastructurally comprised granular
coated fine fibrils 12-24 nm in diameter. To the best of our knowledge, alpha
synuclein-related neuronal pathology localized in the perirhinal region without
hippocampal involvement has not been previously reported in MSA, and may provide
clues to elucidate how neuronal pathology evolves in the
hippocampal/parahippocampal regions in MSA, particularly in cases with dementia.
PMID- 28419568
TI - The influence of noninvasive prenatal testing on gestational age at time of
abortion for aneuploidy.
AB - OBJECTIVE: The objective of this study is to compare the gestational age at
termination for trisomy 13, 18, or 21 (aneuploidy) before and after the
introduction of noninvasive prenatal testing (NIPT). METHODS: A retrospective
cohort of women undergoing termination for aneuploidy at two academic
institutions and one private clinic. We compared two time periods: before and
after the introduction of NIPT (2006-2011 and 2012-2014, respectively). Maternal
demographics and clinical characteristics were abstracted from the medical
record. Nonparametric statistical methods were used to compare the two cohorts.
RESULTS: Our cohort included 93 women: 41 prior to NIPT and 52 post-NIPT.
Maternal age (38 post-NIPT vs 37 pre-NIPT; p = 0.17) did not differ between the
time periods. Women in the post-NIPT were less likely to undergo diagnostic
testing (82.7% vs 97.6%; p < 0.01) before proceeding to abortion after a positive
screening result. In the post-NIPT period, there was a significant decrease in
the gestational age at time of invasive testing (13.0 vs 15.7 weeks; p < 0.01)
and women were more likely to undergo chorionic villous sampling (CVS) (59.6% vs
41.5%; p < 0.01). There was a significant decrease in the gestational age at
termination (14.2 vs 17.2; p < 0.01). Women in the post-NIPT group were less
likely to have terminations after 16 weeks (25.0% vs 61.0%; p < 0.01), 18 weeks
(7.7% vs 39.0%; p < 0.01), or 20 weeks (3.9% vs 12.2%; p = 0.23). CONCLUSION:
With the introduction of NIPT, the median gestational age at diagnosis and
termination for women with Trisomy 13, 18, or 21 was 3 weeks earlier. Women were
four times less likely to have a termination after 18 weeks and three times less
likely to have a termination after 20 weeks. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419569
TI - Lava lake structure and cloud-like structureless area: new clues for diagnosing
extramammary Paget disease.
PMID- 28419567
TI - Cardiorespiratory physiology in the safe passage study: protocol, methods and
normative values in unexposed infants.
AB - AIM: The Safe Passage Study, conducted by the Prenatal Alcohol in SIDS and
Stillbirth Network, is investigating contributions of prenatal alcohol exposure
to foetal and infant demise. This current report presents physiological data from
full-term infants with no prenatal exposure to alcohol or maternal smoking.
METHODS: Data are from 666 infants from the Northern Plains (North and South
Dakota) and South Africa. A standardised protocol assessed cardiorespiratory
function during baseline and head-up tilts shortly after birth and at one month
of age. RESULTS: Analyses revealed significant increases in heart rate and
decreases in BP from the newborn to one-month time period as well as diminished
heart rate responses to head-up tilt in one-month-old infants. CONCLUSION: The
Safe Passage Study was successful in characterising physiology in a large number
of infants at sites known to have elevated risks for SIDS. Results demonstrate
that even with low prenatal adverse exposures, there are significant changes in
cardiorespiratory function as infants enter the window of increased risk for
SIDS.
PMID- 28419570
TI - Oral lichenoid reactions associated with anti-PD-1/PD-L1 therapies:
clinicopathological findings.
PMID- 28419571
TI - Characterization of mesenchymal stem cells in bovine endometrium during
follicular phase of oestrous cycle.
AB - Stem cells have been postulated as responsible for cell regeneration in highly
and continuously regenerative tissues such as the endometrium. Few studies in
cattle have identified and specified the presence of stem cells in the
endometrium during the oestrous cycle. The aim of this study was to investigate
the presence of mesenchymal stem cells (MSCs) in the bovine endometrium during
the follicular phase (FP) of the oestrous cycle. Uterine tissue was collected in
the time-frame comprising day 18 of the cycle and ovulation (day 0). We isolated,
cultured and expanded four primary cell lines from endometrium and identified
byRT-qPCR the expression of OCT4, SOX2 but not NANOG (undifferentiated/embryonic
markers), CD44 (MSCs marker) and c-KIT (stem cell marker) genes; and the encoded
Oct4, Sox2 and Cd44 proteins by Western blot or immunostaining of paraffin
embedded tissue in endometrium. We demonstrated that cells isolated from bovine
endometrium displayed essentially the same gene expression pattern; however, at
the protein level, Oct4 and Cd44 were not detected. Besides, they showed typical
functional characteristics of MSCs such as fibroblast-like morphology, plastic
adherence, high proliferative capacity, clone formation in vitro and the ability
to differentiate into chondrogenic, osteogenic and adipogenic lineages. We
obtained for the first time an extensive characterization of undifferentiated
cells populations contained in the bovine endometrium during the FP of the
oestrous cycle.
PMID- 28419572
TI - Genomewide differential expression profiling of long non-coding RNAs in
androgenetic alopecia in a Chinese male population.
AB - BACKGROUND: Androgenetic alopecia (AGA), or male pattern baldness (MPB), is the
most common form of hair loss in males. A combination of genetic and androgen
causes have been suggested as factors that contribute to the development of AGA.
However, the specific molecular mechanisms that underly AGA remain largely
unknown. Long non-coding RNAs (lncRNAs), a new class of regulatory non-coding
RNAs that are longer than 200 nucleotides, have been shown to play important
roles in a number of cellular processes, including transcription, chromosome
remodelling and post-transcriptional processing. The dysregulation of lncRNAs is
associated with many forms of diseases, but it remains unknown whether lncRNAs
are associated with AGA. OBJECTIVE: The aim of this study was to identify AGA
associated lncRNAs and predict the potential roles of these lncRNAs in AGA.
METHODS: A genomewide microarray was used to identify lncRNAs that are
differentially expressed between AGA and adjacent normal tissues. Real-time qRT
PCR was used to validate the microarray data. RESULTS: A large number of lncRNAs
were differentially expressed (fold change >2.4) between AGA and adjacent normal
tissues. Of these, 770 were upregulated and 1373 were downregulated. Moreover,
pathway analysis revealed that 53 functional pathways were associated with the
upregulated transcripts, while 11 pathways were associated with the downregulated
transcripts. CONCLUSION: To our knowledge, this is the first study to investigate
AGA-associated lncRNAs. lncRNA profiles are altered in AGA, and these lncRNAs and
their target genes may serve as novel candidates for preventing and treating AGA.
PMID- 28419573
TI - Impella 2.5 initiated prior to unprotected left main PCI in acute myocardial
infarction complicated by cardiogenic shock improves early survival.
AB - OBJECTIVES: To assess post-procedural outcomes when Impella 2.5 percutaneous left
ventricular assist device (pLVAD) support is initiated either prior to or after
percutaneous coronary intervention (PCI) on unprotected left main coronary artery
(ULMCA) culprit lesion in the context of acute myocardial infarction cardiogenic
shock (AMICS). BACKGROUND: Initiation of Impella 2.5 pLVAD prior to PCI is
associated with significant survival benefit in the setting of AMICS. Outcomes of
those presenting with a ULMCA culprit lesion in this setting have not been well
characterized. METHODS: Thirty-six consecutive patients in the cVAD Registry
supported with Impella 2.5 pLVAD for AMICS who underwent PCI on ULMCA culprit
lesion were included in our multicenter study. RESULTS: The average age was 69.8
+/- 14.2 years, 77.8% were male, 72.7% were in CS at admission, 44.4% sustained
one or multiple cardiac arrests, and 30.6% had anoxic brain injury. Baseline
characteristics were comparable between the Pre-PCI group (n = 20) and Post-PCI
group (n = 16). Non-ST segment elevation myocardial infarction and greater
coronary disease burden were significantly more frequent in the Pre-PCI group but
they had significantly better survival to discharge (55.0% vs 18.8%, P = 0.041).
Kaplan-Meier 30-day survival analysis showed very poor survival in Post-PCI group
(48.1% vs 12.5%, Log-Rank P = 0.004). CONCLUSIONS: Initiation of Impella 2.5
pLVAD prior to as compared with after PCI of ULMCA for AMICS culprit lesion is
associated with significant early survival. As previously described, patients
supported after PCI appear to have very poor survival at 30 days.
PMID- 28419574
TI - Phototherapy and photochemotherapy for polymorphic light eruption
desensitization: a five-year case series review from a university teaching
hospital.
PMID- 28419575
TI - Prepubertal vulvar fibroma, a rare entity little known to dermatologists: report
of two cases.
PMID- 28419576
TI - Agreement between rapid on-site evaluation and the final cytological diagnosis of
salivary gland specimens.
AB - OBJECTIVE: Rapid on-site evaluation (ROSE) has been shown to be beneficial in
determining the adequacy and a preliminary diagnosis in multiple organ systems.
However, little is known regarding the diagnostic values and agreement of ROSE
compared with a final cytological diagnosis in salivary gland fine needle
aspiration (FNA). The aim of the present study was to evaluate agreement and
compare accuracy between ROSE and a final cytological diagnosis of salivary gland
FNA, using a final histological diagnosis as a gold standard. METHODS: All
patients with salivary gland lesions who underwent FNA with ROSE during 2009 to
2013 were evaluated. The patient demographic data, clinical characteristics,
ROSE, final cytological diagnosis and final histological diagnosis were obtained.
Agreement and accuracy were assessed by Kappa statistic and receiver-operating
characteristic (ROC) curve analysis, respectively. RESULTS: Of 386 FNAs with
ROSE, 248 (64%) lesions were from parotid glands, and 171 (44%) had histological
follow-up results. Agreement between ROSE and the final cytological diagnosis was
good to excellent (simple kappa = 0.76; linear weighted kappa = 0.81). There were
discrepancies in 25 lesions (6.8%). Of these, 10 (2.7%) were major discrepancies,
resulting in a change in clinical management. Only one of 36 malignant lesions by
ROSE was downgraded to suspicious. No significant difference was found in
accuracy between two interpretations (area under the curve 0.82 vs 0.84, P=.17).
CONCLUSION: These findings suggest that, in addition to an excellent agreement
and comparably good accuracy between ROSE and final cytological evaluation,
malignant results of ROSE may be useful to facilitate an early clinical decision.
PMID- 28419577
TI - Decline in new psychoactive substance use disorders following legislation
targeting headshops: Evidence from national addiction treatment data.
AB - INTRODUCTION AND AIMS: New psychoactive substances (NPS) have hedonic effects
that may lead to dependence. Headshops selling NPS increased in number in Ireland
from late 2009. Legislation was enacted in May and August of 2010 that caused
their closure. It is unknown whether such events impact the rate of NPS use
disorders. DESIGNS AND METHODS: We conducted a population-based study using the
Irish national database of episodes of addiction treatment between 2009 and 2012.
We examined trends in the rate of NPS-related treatment episodes among young
adults. Joinpoint trend analysis software was used to identify significant
changes in trend. RESULTS: Of the 31 284 episodes of addiction treatment
commenced by adults aged 18 to 34 years, 756 (2.4%) were NPS related. In 2012,
the 12-month moving average rate had fallen 48% from its peak in 2010, from
9.0/100 000 to 4.7/100 000. Joinpoint analysis indicated that the rate of NPS
related episodes increased by 218% (95% confidence interval 86 to 445, P = 0.001)
every 4 months until the first third of 2010. From that point, the rate declined
by 9.8% (95% confidence interval -14.1 to -5.4, P = 0.001) per 4-month period.
There was no significant trend change in the rate of non-NPS related treatment
episodes. DISCUSSION AND CONCLUSIONS: Over the 2 years after the enactment of
prohibition-styled legislation targeting NPS and headshops, the rate of NPS
related addiction treatment episodes among young adults declined progressively
and substantially. We found no coinciding trend change in the rate of episodes
linked to other drug groups. [Smyth BP, Lyons S, Cullen W. Decline in new
psychoactive substance use disorders following legislation targeting headshops:
Evidence fromnational addiction treatment data. Drug Alcohol Rev 2017;00:000
000].
PMID- 28419578
TI - Disordered eating patterns in coeliac disease: a framework analysis.
AB - OBJECTIVE: The need for dietary-management in coeliac disease may lead to the
development of disordered eating patterns. A theoretical model of disordered
eating has been proposed to explain disordered eating in coeliac disease. The aim
of this study was to explore the experiences of typical and disordered eating in
coeliac disease to gain a greater understanding of these processes and explore
specific pathways within this model. METHODS: We interviewed 21 individuals with
coeliac disease, recruited from a previous database, about their experiences with
food and food environments. Information about disordered eating status was
assessed via questionnaire. The interviews were analysed qualitatively using
Framework analysis, which was underpinned by the theoretical model of disordered
eating in coeliac disease. RESULTS: Experiences differed between participants
scoring high on measures of disordered eating and those who scored low (typical
eaters). Participants scoring high on measures of disordered eating were
concerned about the consequences of their gluten-free diet on body image and they
described eating patterns similar to binge/restrict cycles. Typical eaters
reported being able to integrate their dietary self-management into their daily
lives; however, general concerns around food and cross-contamination were
associated with a restriction in food intake. CONCLUSIONS: Coeliac disease has a
varied impact on eating patterns. The need to follow a gluten-free diet and to be
vigilant around food has to be balanced with concerns around food availability
and cross-contamination which have the potential to contribute towards disordered
eating attitudes and behaviours. The findings suggest that the theoretical model
of disordered eating provides an adequate explanation of disordered eating
patterns in coeliac disease.
PMID- 28419581
TI - Successful kidney transplantation in highly sensitized, ultra-long-term dialysis
patients.
PMID- 28419579
TI - Erdj3 Has an Essential Role for Z Variant Alpha-1-Antitrypsin Degradation.
AB - Alpha-1-antitrypsin deficiency (AATD) is an inherited disease characterized by
emphysema and liver disease. AATD is most often caused by a single amino acid
substitution at amino acid 342 in the mature protein, resulting in the Z mutation
of the alpha-1-antitrypsin gene (ZAAT). This substitution is associated with
misfolding and accumulation of ZAAT in the endoplasmic reticulum (ER) of
hepatocytes and monocytes, causing a toxic gain of function. Retained ZAAT is
eliminated by ER-associated degradation and autophagy. We hypothesized that alpha
1-antitrypsin (AAT)-interacting proteins play critical roles in quality control
of human AAT. Using co-immunoprecipitation, we identified ERdj3, an ER-resident
Hsp40 family member, as a part of the AAT trafficking network. Depleting ERdj3
increased the rate of ZAAT degradation in hepatocytes by redirecting ZAAT to the
ER calreticulin-EDEM1 pathway, followed by autophagosome formation. In the Huh7.5
cell line, ZAAT ER clearance resulted from enhancing ERdj3-mediated ZAAT
degradation by silencing ERdj3 while simultaneously enhancing autophagy. In this
context, ERdj3 suppression may eliminate the toxic gain of function associated
with polymerization of ZAAT, thus providing a potential new therapeutic approach
to the treatment of AATD-related liver disease. J. Cell. Biochem. 118: 3090-3101,
2017. (c) 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley
Periodicals Inc.
PMID- 28419580
TI - Liquid/Liquid Interfacial Synthesis of a Click Nanosheet.
AB - A liquid/liquid interfacial synthesis is employed, for the first time, to
synthesize a covalent two-dimensional polymer nanosheet. Copper-catalyzed azide
alkyne cycloaddition (CuAAC) between a three-way terminal alkyne and azide at a
water/dichloromethane interface generates a 1,2,3-triazole-linked nanosheet. The
resultant nanosheet, with a flat and smooth texture, has a maximum domain size of
20 MUm and minimum thickness of 5.3 nm. The starting monomers in the organic
phase and the copper catalyst in the aqueous phase can only meet at the
liquid/liquid interface as a two-dimensional reaction space; this allows them to
form the two-dimensional polymer. The robust triazole linkage generated by
irreversible covalent-bond formation allows the nanosheet to resist hydrolysis
under both acidic and alkaline conditions, and to endure pyrolysis up to more
than 300 degrees C. The coordination ability of the triazolyl group enables the
nanosheet to act as a reservoir for metal ions, with an affinity order of Pd2+
>Au3+ >Cu2+ .
PMID- 28419582
TI - Free-breathing liver fat quantification using a multiecho 3D stack-of-radial
technique.
AB - PURPOSE: The diagnostic gold standard for nonalcoholic fatty liver disease is an
invasive biopsy. Noninvasive Cartesian MRI fat quantification remains limited to
a breath-hold (BH). In this work, a novel free-breathing 3D stack-of-radial (FB
radial) liver fat quantification technique is developed and evaluated in a
preliminary study. METHODS: Phantoms and healthy subjects (n = 11) were imaged at
3 Tesla. The proton-density fat fraction (PDFF) determined using FB radial (with
and without scan acceleration) was compared to BH single-voxel MR spectroscopy
(SVS) and BH 3D Cartesian MRI using linear regression (correlation coefficient
rho and concordance coefficient rhoc ) and Bland-Altman analysis. RESULTS: In
phantoms, PDFF showed significant correlation (rho > 0.998, rhoc > 0.995) and
absolute mean differences < 2.2% between FB radial and BH SVS, as well as
significant correlation (rho > 0.999, rhoc > 0.998) and absolute mean
differences < 0.6% between FB radial and BH Cartesian. In the liver and abdomen,
PDFF showed significant correlation (rho > 0.986, rhoc > 0.985) and absolute
mean differences < 1% between FB radial and BH SVS, as well as significant
correlation (rho > 0.996, rhoc > 0.995) and absolute mean differences < 0.9%
between FB radial and BH Cartesian. CONCLUSION: Accurate 3D liver fat
quantification can be performed in 1 to 2 min using a novel FB radial technique.
Magn Reson Med 79:370-382, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28419583
TI - Comparison of multifactor scoring systems and single serum markers for the early
prediction of the severity of acute pancreatitis.
AB - BACKGROUND: The purpose of this study was to clarify whether the current scoring
systems and single serum markers used in pancreatitis remain applicable for the
early prediction of infected pancreatic necrosis (IPN) and the severity and
mortality of acute pancreatitis (AP) in accordance with the revised Atlanta and
determinant-based classifications. METHODS: Demographic, clinical, and laboratory
data from 708 consecutive patients with AP were prospectively collected between
January 2011 and December 2012. The severity was classified using the revised
Atlanta and determinant-based classification systems. The predictive accuracies
for moderately severe AP (MSAP), severe AP (SAP), critically severe AP (CAP),
IPN, and mortality were measured using area under the receiver operating
characteristic curves. RESULTS: The receiver operating characteristic analysis
showed that the multifactor scoring systems and single serum markers had a low
predictive accuracy regarding moderately severe AP. The Acute Physiology and
Chronic Health Evaluation (APACHE) II score had the highest accuracy in
predicting SAP with area under the curve (AUC) values of 0.75 (95% CI = 0.71
0.79) and 0.77 (95% CI = 0.73-0.81) at 24 and 48 h after admission, respectively.
Procalcitonin was the most accurate predictor for CAP and IPN, with respective
AUCs of 0.86 (95% CI = 0.82-0.89) and 0.83 (95% CI = 0.78-0.87) at 48 h after
admission. In predicting mortality, both the APACHE II score and blood urea
nitrogen had the highest accuracy. CONCLUSIONS: The APACHE II score had the
highest predictive accuracy for SAP and mortality as defined by the revised
Atlanta classification, whereas procalcitonin was the most accurate predictor for
CAP and IPN.
PMID- 28419584
TI - Context-dependent function of ROS in the vascular endothelium: The role of the
Notch pathway and shear stress.
AB - Reactive oxygen species (ROS) act as signal molecules in several biological
processes whereas excessive, unregulated, ROS production contributes to the
development of pathological conditions including endothelial dysfunction and
atherosclerosis. The maintenance of a healthy endothelium depends on many factors
and on their reciprocal interactions; in this framework, the Notch pathway and
shear stress (SS) play two lead roles. Recently, evidence of a crosstalk between
ROS, Notch, and SS, is emerging. The aim of this review is to describe the way
ROS interact with the Notch pathway and SS protecting from-or promoting-the
development of endothelial dysfunction. (c) 2017 BioFactors, 43(4):475-485, 2017.
PMID- 28419585
TI - A new discrepancy of HPA-3 genotyping because of a rare HPA-27bw polymorphism.
PMID- 28419586
TI - A review of the nutritional challenges experienced by people living with severe
mental illness: a role for dietitians in addressing physical health gaps.
AB - People experiencing a severe mental illness (SMI), such as schizophrenia,
schizoaffective disorder, bipolar affective disorder or depression with psychotic
features, have a 20-year mortality gap compared to the general population. This
'scandal of premature mortality' is primarily driven by preventable
cardiometabolic disease, and recent research suggests that the mortality gap is
widening. Multidisciplinary mental health teams often include psychiatrists,
clinical psychologists, specialist mental health nurses, social workers and
occupational therapists, offering a range of pharmacological and
nonpharmacological treatments to enhance the recovery of clients who have
experienced, or are experiencing a SMI. Until recently, lifestyle and life skills
interventions targeting the poor physical health experienced by people living
with SMI have not been offered in most routine clinical settings. Furthermore,
there are calls to include dietary intervention as mainstream in psychiatry to
enhance mental health recovery. With the integration of dietitians being a
relatively new approach, it is important to review and assess the literature to
inform practice. This review assesses the dietary challenges experienced by
people with a SMI and discusses potential strategies for improving mental and
physical health.
PMID- 28419587
TI - An oligogalacturonide-derived molecular probe demonstrates the dynamics of
calcium-mediated pectin complexation in cell walls of tip-growing structures.
AB - Pectic homogalacturonan (HG) is one of the main constituents of plant cell walls.
When processed to low degrees of esterification, HG can form complexes with
divalent calcium ions. These macromolecular structures (also called egg boxes)
play an important role in determining the biomechanics of cell walls and in
mediating cell-to-cell adhesion. Current immunological methods enable only steady
state detection of egg box formation in situ. Here we present a tool for
efficient real-time visualisation of available sites for HG crosslinking within
cell wall microdomains. Our approach is based on calcium-mediated binding of
fluorescently tagged long oligogalacturonides (OGs) with endogenous de-esterified
HG. We established that more than seven galacturonic acid residues in the HG
chain are required to form a stable complex with endogenous HG through calcium
complexation in situ, confirming a recently suggested thermodynamic model. Using
defined carbohydrate microarrays, we show that the long OG probe binds
exclusively to HG that has a very low degree of esterification and in the
presence of divalent ions. We used this probe to study real-time dynamics of HG
during elongation of Arabidopsis pollen tubes and root hairs. Our results suggest
a different spatial organisation of incorporation and processing of HG in the
cell walls of these two tip-growing structures.
PMID- 28419588
TI - Endoscopic treatment of intraductal pancreatic stent fragmentation.
AB - BACKGROUND AND AIM: Complications of endoscopic treatment are reported more and
more often as a result of popularization of pancreatic endotherapy. Our study
presents the results of treatment in patients with intraductal pancreatic stent
fragmentation diagnosed during endotherapy of chronic pancreatitis. METHODS:
Retrospective analysis of 2496 endoscopic retrograde cholangiopancreatography
procedures which were carried out in 607 patients at the Gastrointestinal
Endoscopy Unit of the University Clinical Center in Gdansk. RESULTS: In the
course of pancreatic endotherapy, intraductal pancreatic stent fragmentation was
stated during 33 of 2496 (0.013%) procedures in 33 of 607 (5.44%) patients with
chronic pancreatitis. In 33 patients, there were 46 intraductal fragments of
broken stents. Most patients were asymptomatic. In 31/33 patients, fragments of
broken stents were removed from the pancreatic duct endoscopically. In the case
of two patients, endoscopic management was ineffective and they were treated
surgically. Altogether, 44/46 stent fragments were removed endoscopically. Most
fragments of pancreatic stents were removed during the first endoscopic
procedure. One fragment of a broken stent was retrieved with polypectomy snare
and four with Dormia basket. The remaining fragments of broken pancreatic stents
were removed with rat-tooth forceps. CONCLUSIONS: Intraductal fragmentation of
pancreatic stent is a rare complication of pancreatic endotherapy and it often
has an asymptomatic course. Most fragments of broken pancreatic stents can be
removed endoscopically from the pancreatic duct with an acceptable complication
rate.
PMID- 28419589
TI - Child health in Sweden is characterised by good health and low accidents, but
rising psychological problems.
PMID- 28419590
TI - Cracking the neural code, treating paralysis and the future of bioelectronic
medicine.
AB - The human nervous system is a vast network carrying not only sensory and movement
information, but also information to and from our organs, intimately linking it
to our overall health. Scientists and engineers have been working for decades to
tap into this network and 'crack the neural code' by decoding neural signals and
learning how to 'speak' the language of the nervous system. Progress has been
made in developing neural decoding methods to decipher brain activity and
bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and
for diagnosing brain-related diseases such as Parkinson's and Alzheimer's
disease. In a recent first-in-human study involving paralysis, a paralysed male
study participant regained movement in his hand, years after his injury, through
the use of a bioelectronic neural bypass. This work combined neural decoding and
neurostimulation methods to translate and re-route signals around damaged neural
pathways within the central nervous system. By extending these methods to
decipher neural messages in the peripheral nervous system, status information
from our bodily functions and specific organs could be gained. This, one day,
could allow real-time diagnostics to be performed to give us a deeper insight
into a patient's condition, or potentially even predict disease or allow early
diagnosis. The future of bioelectronic medicine is extremely bright and is wide
open as new diagnostic and treatment options are developed for patients around
the world.
PMID- 28419591
TI - Application of spin echoes in the regime of weak dephasing to T1 -mapping of the
lung.
AB - PURPOSE: This work presents an approach to mapping the entire lung's proton
density and T1 within a single breath-hold and analyzes the apparent T1 when
exciting with a spin echo generating pulse in comparison to a standard gradient
echo acquisition. METHODS: An inversion-recovery SNAPSHOT-FLASH sequence with a
stack-of-stars k-space readout with a golden angle increment was modified to use
a spin echo generating radiofrequency-pulse for excitation. Data of five
volunteers were acquired on a 3T scanner and image reconstruction was performed
by an iterative algorithm adopted from MR-Fingerprinting. RESULTS: The
feasibility of acquiring quantitative maps of the entire lung with a resolution
of 5 * 5 * 10 mm within 7.5 s is demonstrated. It is shown that the proposed spin
echo forming radiofrequency-pulse increases the apparent proton density compared
to a rectangular pulse. Further, the apparent T1 is reduced in the spin echo case
compared to the gradient echo sequence. CONCLUSION: The proposed spin echo based
method results in T1 maps that are comparable to the ones that were acquired with
ultra-short echo time sequences elsewhere. The T1 shortening is believed to
originate from increased signal contributions of the extra vascular compartment,
which has a short T2* and T1 . Magn Reson Med 79:960-967, 2018. (c) 2017
International Society for Magnetic Resonance in Medicine.
PMID- 28419592
TI - Catalyst Optimisation for Asymmetric Synthesis by Ligand Chirality Element
Addition: A Perspective on Stereochemical Cooperativity.
AB - The concept of matched and mismatched stereochemical pairings has been utilised
extensively in organic synthesis, with the cooperativity resulting from the
former enabling many reactions to proceed with high stereoselectivity. This
approach was first developed to improve the diastereoselectivity of a reaction by
matching the configuration of an enantiopure reagent or catalyst with the
configuration of an enantiopure substrate. It has been extended to the asymmetric
transformation of prochiral substrates controlled by reagents and catalysts
containing two or more stereogenic centres. Matched and mismatched pairings may
again be identified, with the former resulting in higher product
enantioselectivity. This Minireview examines stereochemical pairings within
catalysts generated from the combination of a metal with an enantiopure ligand;
specifically examples in which the ligand diastereoisomers examined for
cooperativity are formally the result of the addition of a chiral element to an
existing enantiopure ligand. Comparison of all three ligands in each of the fifty
six examples examined reveals that, in the majority of cases, the added element
of chirality increases and decreases the enantioselectivity with respect to the
parent ligand. The iterative application of this effect offers a potentially
powerful method for catalyst optimisation for use in asymmetric synthesis.
PMID- 28419594
TI - Catheter ablation for the treatment of atrial fibrillation is associated with a
reduction in health care resource utilization.
AB - BACKGROUND: Catheter ablation (CA) is superior to antiarrhythmic therapy at
reducing recurrence of atrial fibrillation (AF); however, there are limited data
regarding whether this decrease translates into a reduction in health care
resource utilization. OBJECTIVE: To evaluate the impact of AF ablation on long
term health care resource utilization. METHODS: A population-based cohort was
constructed to include patients who underwent CA for AF in Quebec, Canada,
between April 2005 and March 2011. Resource utilization was evaluated 24 months
pre- and postindex CA procedure. RESULTS: In a cohort of 1,556 patients, resource
utilization increased progressively over the 24-month period leading to index CA
(P for trend <0.05 for hospitalizations, ER visits, outpatient visits,
cardioversions, and echocardiograms). After index CA, all-cause hospitalizations,
hospitalizations for AF, ER visits, cardioversions, and echocardiograms were
reduced 12 months post-CA compared to 12 months prior (all-cause hospitalizations
0.8-0.6 per patient per year; hospitalizations for AF 0.4-0.3; ER visits 2.9-1.8;
cardioversions 0.5-0.2; echocardiograms 0.8-0.5; P < 0.05 for all trends).
Resource utilization continued to decline at 24 months post-CA (vs. 12 months
prior) for all-cause hospitalizations (0.4), cardioversions (0.1), and
echocardiograms (0.3) (per patient year; P < 0.05 for all trends). CONCLUSION: In
conclusion, the pattern of increasing health care resource utilization preceding
CA for AF reverses after CA to lower than preablation levels up to 24 months post
CA.
PMID- 28419593
TI - Protein sumoylation and phosphorylation intersect in Arabidopsis signaling.
AB - Conjugation of the small ubiquitin-related modifier (SUMO) to protein substrates
has an impact on stress responses and on development. We analyzed the proteome
and phosphoproteome of mutants in this pathway. The mutants chosen had defects in
SUMO ligase SIZ1, which catalyzes attachment of single SUMO moieties onto
substrates, and in ligases PIAL1 and PIAL2, which are known to form SUMO chains.
A total of 2657 proteins and 550 phosphopeptides were identified and quantified.
Approximately 40% of the proteins and 20% of the phosphopeptides showed
differences in abundance in at least one of the analyzed genotypes, demonstrating
the influence of SUMO conjugation on protein abundance and phosphorylation. The
data show that PIAL1 and PIAL2 are integral parts of the SUMO conjugation system
with an impact on stress response, and confirm the involvement of SIZ1 in plant
defense. We find a high abundance of predicted SUMO attachment sites in
phosphoproteins (70% versus 40% in the total proteome), suggesting convergence of
phosphorylation and sumoylation signals onto a set of common targets.
PMID- 28419596
TI - Effects of culture conditions on the size, morphology and wet density of spores
of Bacillus cereus 569 and Bacillus megaterium QM B1551.
AB - : The influence of variable culture conditions on the size and wet density of
spores of Bacillus cereus and Bacillus megaterium were examined in this work.
Culture temperature and initial pH was shown to have a significant impact on the
size of both species, with increasingly alkaline culture media and elevated
culture temperatures resulting in spores that were, on average, up to 25% reduced
in volume. Increasing concentrations of inorganic salts in sporulation media
exerted differing effects on each species; whereas a fivefold increase in the
concentration of all salts resulted in only minor differences to the dimensions
of B. cereus spores, B. megaterium spores became more elongated, displaying an
average increase in volume of almost 30%. Similarly, as the spore elongated to
yield aspect ratios larger than 1.4, their shape changed from typical prolate
spheroids to cylinders with hemispherical ends. In contrast with previous
studies, culture conditions employed in this study exerted no discernible impact
on the wet density of B. cereus or B. megaterium spores. SIGNIFICANCE AND IMPACT
OF THE STUDY: Bacterial spores of the genera Bacillus and Clostridium represent
nature's most durable cells in terms of their extreme resistance to a variety of
deleterious environments. As a result, they are of concern in the food
processing, healthcare and other sectors, and are of increasing biotechnological
interest. Improved understanding of variance in spore size, morphology and
density may aid the development of certain spore-associated applications (e.g.
spore surface display) while contributing to active areas of research such as
spore adhesion and resistance to heat.
PMID- 28419595
TI - Lipopolysaccharide binding to the periplasmic protein LptA.
AB - Lipopolysaccharide (LPS) and the periplasmic protein, LptA, are two essential
components of Gram-negative bacteria. LPS, also known as endotoxin, is found
asymmetrically distributed in the outer leaflet of the outer membrane of Gram
negative bacteria such as Escherichia coli and plays a role in the organism's
natural defense in adverse environmental conditions. LptA is a member of the
lipopolysaccharide transport protein (Lpt) family, which also includes LptC,
LptDE, and LptBFG2 , that functions to transport LPS through the periplasm to the
outer leaflet of the outer membrane after MsbA flips LPS across the inner
membrane. It is hypothesized that LPS binds to LptA to cross the periplasm and
that the acyl chains of LPS bind to the central pocket of LptA. The studies
described here are the first to comprehensively characterize and quantitate the
binding of LPS by LptA. Using site-directed spin-labeling electron paramagnetic
resonance (EPR) spectroscopy, data were collected for 15 spin-labeled residues in
and around the proposed LPS binding pocket on LptA to observe the mobility
changes caused by the presence of exogenous LPS and identify the binding location
of LPS to LptA. The EPR data obtained suggest a 1:1 ratio for the LPS:LptA
complex and allow the first calculation of dissociation constants for the LptA
LPS interaction. The results indicate that the entire protein is affected by LPS
binding, the N-terminus unfolds in the presence of LPS, and a mutant LptA protein
unable to form oligomers has an altered affinity for LPS.
PMID- 28419597
TI - Growth rate correlates negatively with protein turnover in Arabidopsis
accessions.
AB - Previous studies with Arabidopsis accessions revealed that biomass correlates
negatively to dusk starch content and total protein, and positively to the
maximum activities of enzymes in photosynthesis. We hypothesized that large
accessions have lower ribosome abundance and lower rates of protein synthesis,
and that this is compensated by lower rates of protein degradation. This would
increase growth efficiency and allow more investment in photosynthetic machinery.
We analysed ribosome abundance and polysome loading in 19 accessions, modelled
the rates of protein synthesis and compared them with the observed rate of
growth. Large accessions contained less ribosomes than small accessions, due
mainly to cytosolic ribosome abundance falling at night in large accessions. The
modelled rates of protein synthesis resembled those required for growth in large
accessions, but were up to 30% in excess in small accessions. We then employed 13
CO2 pulse-chase labelling to measure the rates of protein synthesis and
degradation in 13 accessions. Small accessions had a slightly higher rate of
protein synthesis and much higher rates of protein degradation than large
accessions. Protein turnover was negligible in large accessions but equivalent to
up to 30% of synthesised protein day-1 in small accessions. We discuss to what
extent the decrease in growth in small accessions can be quantitatively explained
by known costs of protein turnover and what factors may lead to the altered
diurnal dynamics and increase of ribosome abundance in small accessions, and
propose that there is a trade-off between protein turnover and maximisation of
growth rate.
PMID- 28419598
TI - Biological traits, rather than environment, shape detection curves of large
vertebrates in neotropical rainforests.
AB - Line transect surveys are widely used in Neotropical rainforests to estimate the
population abundance of medium- and large-sized vertebrates. The use of indices
such as encounter rate has been criticized because the probability of animal
detection may fluctuate due to the heterogeneity of environmental conditions
among sites. In addition, the morphological and behavioral characteristics
(biological traits) of species affect their detectability. In this study, we
compared the extent to which environmental conditions and species' biological
traits bias abundance estimates in terra firme rainforests in French Guiana. The
selected environmental conditions included both physical conditions and forest
structure covariates, while the selected biological traits included the
morphological and behavioral characteristics of species. We used the distance
sampling method to model the detection probability as an explicit function of
environmental conditions and biological traits and implemented a model selection
process to determine the relative importance of each group of covariates.
Biological traits contributed to the variability of animal detectability more
than environmental conditions, which had only a marginal effect. Detectability
was best for large animals with uniform or disruptive markings that live in
groups in the canopy top. Detectability was worst for small, solitary,
terrestrial animals with mottled markings. In the terra firme rainforests that
represent ~80% of the Amazonia and Guianas regions, our findings support the use
of relative indices such as the encounter rate to compare population abundance
between sites in species-specific studies. Even though terra firme rainforests
may appear similar between regions of Amazonia and the Guianas, comparability
must be ensured, especially in forests disturbed by human activity. The detection
probability can be used as an indicator of species' vulnerability to hunting and,
thus, to the risk of local extinction. Only a few biological trait covariates are
required to correctly estimate the detectability of the majority of medium- and
large-sized vertebrates. Thus, a biological trait model could be useful in
predicting the detection probabilities of rare, uncommon, or localized species
for which few data are available to fit the detection function.
PMID- 28419600
TI - Reformulations of well-known active ingredients in the topical treatment of
psoriasis vulgaris can improve clinical outcomes for patients.
AB - Although the majority of patients with psoriasis vulgaris are treated exclusively
with topical therapies, research to develop more effective topical therapies that
are associated with higher patient satisfaction has lagged behind the development
of systemic agents. The aim of this literature review was to determine whether
there is documented evidence that applying an innovative approach to improving
the formulation of active ingredients commonly used in the topical treatment of
psoriasis can have a positive effect on clinical outcomes and patient-reported
outcomes (PROs). The Embase and PubMed databases were searched for articles
published between 2001 and 2016 that made direct head-to-head comparisons of
different formulations of an active pharmaceutical ingredient (API), focusing on
clinical outcomes and PROs. In total, 22 publications on APIs or API combinations
met the eligibility criteria (19 head-to-head clinical trials, one pooled
analysis, one health-economic modelling study and one systematic review).
Significant clinical benefit associated with the use of a reformulated API over
an older formulation was reported in three trials of clobetasol propionate, one
trial of calcipotriol, three trials of betamethasone and five trials/pooled
analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD)
formulations. Significantly improved PROs associated with the use of a
reformulated API over an older formulation were reported in three trials of
clobetasol propionate, one trial of betamethasone valerate and two trials of
Cal/BD formulations. These results demonstrate that the innovative reformulation
of APIs used in the treatment of psoriasis can produce therapies that attain
significantly improved clinical outcomes and PROs. This suggests that improvement
in topical therapy for psoriasis need not only to be achieved by the
identification of new targets and the development of new APIs, but that
improvement in the vehicle used to deliver existing APIs has the potential to
result in significant clinical and patient benefits.
PMID- 28419601
TI - Is high-flow nasal cannula noninferior to nasal CPAP for the initial management
of preterm infants?
PMID- 28419599
TI - Mycobacterium tuberculosis proteasomal ATPase Mpa has a beta-grasp domain that
hinders docking with the proteasome core protease.
AB - Mycobacterium tuberculosis (Mtb) has a proteasome system that is essential for
its ability to cause lethal infections in mice. A key component of the system is
the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds,
and translocates protein substrates into the Mtb proteasome core particle for
degradation. Here, we report the crystal structures of near full-length hexameric
Mtb Mpa in apo and ADP-bound forms. Surprisingly, the structures revealed a
ubiquitin-like beta-grasp domain that precedes the proteasome-activating carboxyl
terminus. This domain, which was only found in bacterial proteasomal ATPases,
buries the carboxyl terminus of each protomer in the central channel of the
hexamer and hinders the interaction of Mpa with the proteasome core protease.
Thus, our work reveals the structure of a bacterial proteasomal ATPase in the
hexameric form, and the structure finally explains why Mpa is unable to stimulate
robust protein degradation in vitro in the absence of other, yet-to-be-identified
co-factors.
PMID- 28419602
TI - Physics for clinicians: Fluid-attenuated inversion recovery (FLAIR) and double
inversion recovery (DIR) Imaging.
AB - : A pedagogical review of fluid-attenuated inversion recovery (FLAIR) and double
inversion recovery (DIR) imaging is conducted in this article. The basics of the
two pulse sequences are first described, including the details of the inversion
preparation and imaging sequences with accompanying mathematical formulae for
choosing the inversion time in a variety of scenarios for use on clinical MRI
scanners. Magnetization preparation (or T2prep), a strategy for improving image
signal-to-noise ratio and contrast and reducing T1 weighting at high field
strengths, is also described. Lastly, image artifacts commonly associated with
FLAIR and DIR are described with clinical examples, to help avoid misdiagnosis.
LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
2017;46:1590-1600.
PMID- 28419604
TI - Predicting the difficulty of a transvenous lead extraction procedure: Validation
of the LED index.
AB - INTRODUCTION: A lead extraction difficulty (LED) score was proposed to predict
the difficult transvenous lead extraction (TLE) procedures, defined by means of
the fluoroscopy time. The aim of this study was to validate the estimation model
based on the LED index above 10 on an independent data set of TLE cases. METHODS:
Consecutive patients undergoing TLE between January 2014 and January 2016 were
included in this analysis. The fluoroscopy time related to the leads removal was
dichotomized as above or below its 90th percentile (PCTL). RESULTS: In total, 446
permanent leads were removed during 233 TLE procedures. Complete procedural
success was achieved in 232 (99.1%) patients. The LED index resulted >10 in
83(35.6%) procedures. Among these cases, 20 had fluoroscopy time above the 90th
PCTL (23.3 minutes) and were classified as true positive. Over the 150 procedures
with LED score <10, 147 were classified as true negative, and only 3 resulted
false negative. The sensitivity, the specificity, and the negative predictive
value of the LED index in predicting complex cases resulted 86.9 (confidence
interval [CI] 66.4-97.2)%, 70.0 (CI 63.3-76.1)%, and 98.0 (CI 94.3-99.6)%,
respectively. The multivariate logistic regression analysis confirmed a 12%
increased risk of high fluoroscopy for each additional point of the LED score (OR
1.12, CI 1.05-1.21, P = 0.001). CONCLUSION: The validation of the estimation
model based on the LED index <10 confirmed its high efficacy in predicting simple
TLE procedures.
PMID- 28419605
TI - Radiofrequency catheter ablation of atrial fibrillation: Electrical modification
suggesting transmurality is faster achieved with remote magnetic catheter in
comparison with contact force use.
AB - BACKGROUND: Remote magnetic navigation (RMN) and contact force (CF) sensing
catheters are available technologies for radiofrequency (RF) catheter ablation of
atrial fibrillation (AF). Our purpose was to compare time to electrogram (EGM)
modification suggesting transmural lesions between RMN and CF-guided AF ablation.
METHODS AND RESULTS: A total of 1,008 RF applications were analyzed in 21
patients undergoing RMN (n = 11) or CF-guided ablation (n = 10) for paroxysmal
AF. All procedures were performed in sinus rhythm during general anesthesia. Time
to EGM modification was measured until transmurality criteria were fulfilled: (1)
complete disappearance of R if initial QR morphology; (2) diminution > 75% of R
if initial QRS morphology; (3) complete disappearance of R' of initial RSR'
morphology. Impedance drop as well as force time integral (FTI) were also
assessed for each application. Mean CF at the beginning of each RF application in
the CF group was 11 +/- 2 g and mean FTI per application was 488 +/- 163 gs. Time
to EGM modification was significantly shorter in the RMN group (4.52 +/- 0.1
seconds vs. 5.6 +/- 0.09 seconds; P < 0.00001). There was no significant
difference between other procedural parameters. CONCLUSION: Remote magnetic AF
ablation is associated with faster EGM modification suggesting transmurality than
optimized CF and FTI-guided catheter ablation.
PMID- 28419603
TI - Assembly and activation of the Escherichia coli divisome.
AB - Cell division in Escherichia coli is mediated by a large protein complex called
the divisome. Most of the divisome proteins have been identified, but how they
assemble onto the Z ring scaffold to form the divisome and work together to
synthesize the septum is not well understood. In this review, we summarize the
latest findings on divisome assembly and activation as well as provide our
perspective on how these two processes might be regulated.
PMID- 28419606
TI - Stratified polygenic risk prediction model with application to CAGI bipolar
disorder sequencing data.
AB - Genetic data consists of a wide range of marker types, including common, low
frequency, and rare variants. Multiple genetic markers and their interactions
play central roles in the heritability of complex disease. In this study, we
propose an algorithm that uses a stratified variable selection design by genetic
architectures and interaction effects, achieved by a dataset-adaptive W-test. The
polygenic sets in all strata were integrated to form a classification rule. The
algorithm was applied to the Critical Assessment of Genome Interpretation 4
bipolar challenge sequencing data. The prediction accuracy was 60% using genetic
markers on an independent test set. We found that epistasis among common genetic
variants contributed most substantially to prediction precision. However, the
sample size was not large enough to draw conclusions for the lack of
predictability of low-frequency variants and their epistasis.
PMID- 28419608
TI - Multiple breath-hold proton spectroscopy of human liver at 3T: Relaxation times
and concentrations of glycogen, choline, and lipids.
AB - PURPOSE: To evaluate the feasibility of an expiration multiple breath-hold 1 H
MRS technique to measure glycogen (Glycg), choline-containing compounds (CCC),
and lipid relaxation times T1 , T2 , and their concentrations in normal human
liver. MATERIALS AND METHODS: Thirty healthy volunteers were recruited.
Experiments were performed at 3T. Multiple expiration breath-hold single-voxel
point-resolved spectroscopy (PRESS) technique was used for localization. Water
suppressed spectra were used for the estimation of Glycg, CCC, lipid methylene
(CH2 )n relaxation times and concentrations. Residual water lines were removed by
the Hankel Lanczos singular value decomposition filter. After phase correction
and frequency alignment, spectra were averaged and processed by LCModel. Summed
signals of Glycg resonances H2H4', H3, and H5 between 3.6 and 4 ppm were used to
estimate their apparent relaxation times and concentration. Glycg, CCC, and lipid
content were estimated from relaxation corrected spectral intensity ratios to
unsuppressed water line. RESULTS: Relaxation times were measured for liver Glycg
(T1 , 892 +/- 126 msec; T2 , 13 +/- 4 msec), CCC (T1 , 842 +/- 75 msec; T2 , 50
+/- 5 msec), lipid (CH2 )n (T1 , 402 +/- 19 msec; T2 , 52 +/- 3 msec), and water
(T1 , 990 +/- 89 msec; T2 , 30 +/- 2 msec). Mean CCC and lipid concentrations of
healthy liver were 7.8 +/- 1.3 mM and 15.8 +/- 23.6 mM, respectively. Glycg
content was found lower in the morning (48 +/- 21 mM) compared to the afternoon
(145 +/- 50 mM). CONCLUSION: Multiple breath-hold 1 H-MRS together with dedicated
postprocessing is a feasible technique for the quantification of liver Glycg,
CCC, and lipid relaxation times and concentrations. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:410-417.
PMID- 28419607
TI - Subjective and objective sleep quality modulate emotion regulatory brain function
in anxiety and depression.
AB - BACKGROUND: Disturbances in emotion regulation and sleep are shared across
anxiety and mood disorders. Poor sleep has been shown to impair cognitive
processes which may undermine cognitive regulatory function. However, it remains
unknown if sleep quality impacts regulatory mechanisms in clinical anxiety and
depression. METHODS: During fMRI, 78 patients with social anxiety disorder,
generalized anxiety disorder, and/or major depressive disorder completed a
validated emotion regulation task, which involved reappraisal (i.e., decrease
negative affect) as compared to viewing aversive images. Sleep quality was
assessed with the Pittsburgh Sleep Quality Index (PSQI) and actigraphy,
representing subjective and objective measures of sleep, respectively. Regression
analysis was conducted with the PSQI and actigraphy sleep efficiency, duration,
and wake-after sleep onset variables. RESULTS: PSQI and actigraphy measures
indicated that the majority of patients experienced problematic sleep, however,
subjective and objective sleep measures were uncorrelated. Whole-brain voxel-wise
regression analysis, controlling for diagnosis, revealed worse self-reported
sleep corresponded with less reappraise-related activation in the dorsal anterior
cingulate cortex (DACC). The same analysis performed with actigraphy data showed
less sleep efficiency positively corresponded with DACC activation. Post-hoc
stepwise regression analysis showed these sleep measures predicted DACC activity
whereas anxiety and depression symptoms did not. CONCLUSIONS: Individual
differences in self-perceived and objective sleep quality differentially
modulated the DACC, which is implicated in cognitive reappraisal. Findings
suggest neural correlates of emotion regulation tracks different aspects of the
sleep experience. Results also indicate sleep disturbance may play a role in the
emotion dysregulation observed in anxiety and depressive disorders.
PMID- 28419609
TI - Band-aids for Buchnera and B vitamins for all.
AB - Evolution lacks foresight, and hence, key adaptations may produce major
challenges over the long run. The natural world is rife with examples of long
term 'side effects' associated with quick-fix tinkering, including blind spots in
vertebrate eyes. An important question is how nature compensates for
imperfections once evolution has set a course. The symbioses associated with sap
feeding insects present a fascinating opportunity to address this issue. On one
hand, the substantial diversity and biomass of sap-feeding insects are largely
due to ancient acquisitions of nutrient-provisioning bacterial symbionts. Yet,
the insularity and small population sizes enforced by intracellular life and
strict maternal transfer inevitably result in the degradation of symbiont genomes
and, often, the beneficial services that symbionts provide. Stabilization through
lateral transfer of bacterial genes into the host nucleus (often from exogenous
sources) or replacement of the long-standing symbiont with a new partner are
potential solutions to this evolutionary dilemma (Bennett & Moran ). A third
solution is adoption of a cosymbiont that compensates for specific losses in the
original resident. Ancient 'co-obligate' symbiont pairs in mealybugs,
leafhoppers, cicadas and spittlebugs show colocalization, codiversification,
metabolite exchange and generally nonredundant nutrient biosynthesis (Bennett &
Moran ). But in this issue, Meseguer et al. () report on a different flavour of
cosymbiosis among conifer-feeding Cinara aphids.
PMID- 28419610
TI - Corrigendum.
PMID- 28419611
TI - Well-being therapy in depression: New insights into the role of psychological
well-being in the clinical process.
AB - A specific psychotherapeutic strategy for increasing psychological well-being and
resilience, well-being therapy (WBT), has been developed and validated in a
number of randomized controlled trials. The findings indicate that flourishing
and resilience can be promoted by specific interventions leading to a positive
evaluation of one's self, a sense of continued growth and development, the belief
that life is purposeful and meaningful, the possession of quality relations with
others, the capacity to manage effectively one's life, and a sense of self
determination. The evidence supporting the use of WBT and its specific
contribution when it is combined with other psychotherapeutic techniques is still
limited. However, the insights gained by the use of WBT may unravel innovative
approaches to assessment and treatment of mood and anxiety disorders, to be
confirmed by controlled studies, with particular reference to decreasing
vulnerability to relapse and modulating psychological well-being and mood. An
important characteristic of WBT is self-observation of psychological well-being
associated with specific homework. Such perspective is different from
interventions that are labeled as positive but are actually distress oriented.
Another important feature of WBT is the assumption that imbalances in well-being
and distress may vary from one illness to another and from patient to patient.
Customary clinical taxonomy and evaluation do not include psychological well
being, which may demarcate major prognostic and therapeutic differences among
patients who otherwise seem to be deceptively similar since they share the same
diagnosis.
PMID- 28419612
TI - Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping of talar
osteochondral lesions: Indicators of clinical outcomes.
AB - PURPOSE: To evaluate the utility of delayed gadolinium-enhanced magnetic
resonance imaging of cartilage (dGEMRIC) and T2 mapping in evaluation of type II
osteochondral lesions (OCLs) of the talus and define cutoff values for
identifying patients with good/poor clinical outcomes. MATERIALS AND METHODS: 28
patients (mean age, 42.3 years) underwent T2 mapping and dGEMRIC at least 1.5
years (mean duration, 3.5 years) after microfracture (n = 12) or conservative (n
= 16) treatment for type II OCL. Clinical outcomes were considered good with an
American Orthopedic Foot and Ankle Society score >=80. The T1 /T2 -values and
indices of repair tissue (RT; cartilage above the OCL) were compared to those of
the adjacent normal cartilage (NC) by region-of-interest analysis. The ability of
the two methods to discriminate RT from NC was determined by area under the
receiver operating characteristics curve (AUC) analysis. The Youden index was
maximized for T1 /T2 measures for identifying cutoff values indicative of
good/poor clinical outcomes. RESULTS: Repair tissue exhibited lower dGEMRIC
values (629.83 vs. 738.51 msec) and higher T2 values (62.07 vs. 40.69 msec) than
NC (P < 0.001). T2 mapping exhibited greater AUC than dGEMRIC (0.88 vs. 0.69; P =
0.0398). All T1 measures exhibited higher maximized Youden indices than the
corresponding T2 measures. The highest maximized Youden index for T1difference
was observed at a cutoff value of 84 msec (sensitivity, 78%; specificity, 83%).
CONCLUSION: While T2 mapping is superior to dGEMRIC in discriminating RT, the
latter better identifies good/poor clinical outcomes in patients with type II
talar OCL. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson.
Imaging 2017;46:1601-1610.
PMID- 28419613
TI - PEG-poly(L-lysine)-based polymeric micelle MRI contrast agent: Feasibility study
of a Gd-micelle contrast agent for MR lymphography.
AB - PURPOSE: To investigate the feasibility of polymeric micelle of
poly(ethyleneglycol) (PEG)-b-poly(L-lysine-DOTA) (Gd-micelle) as a contrast agent
for magnetic resonance lymphography (MRL). MATERIALS AND METHODS: Twenty-four
female BALB/c mice were randomly divided into four groups of six mice each. Among
them, mice of two groups were injected of complete Freund's adjuvant to obtain
inflamed lymph nodes. We subcutaneously injected 0.5 MUmol Gd per mouse of Gd
micelle or gadofluorine P in the right rear footpad. Identical 3D T1 -weighted
gradient-echo imaging (1T MRI system) were subsequently obtained to create time
intensity curves of the right popliteal, sacral, and lumbar-aortic lymph nodes
and to measure the contrast ratios (CRs). The peak CR, area under the curve
(AUC), and elimination half-life (T1/2 ) of CR of the popliteal lymph node were
assessed by two-way factorial analysis of variance. We also performed a
qualitative assessment of normal and inflamed lymph node at three timepoints.
RESULTS: The mean peak CR of Gd-micelle was 2.64 and 1.89 for gadofluorine P in
normal mice, and 3.48 and 2.73 in the inflamed lymph node. Statistically, peak CR
was higher for Gd-micelle (P = 0.004). In addition, the AUC was larger (P <
0.001) and T1/2 was longer (P < 0.001) for Gd-micelle. In qualitative assessment,
Gd-micelle demonstrated the same or higher scores in every lymph node, and
demonstrated a higher score in lumbar-aortic lymph node of a 360-minute image (P
= 0.006) and in inflamed lymph node of a 360-minute image (P = 0.009).
CONCLUSION: Compared to gadofluorine P, Gd-micelle showed higher and more
prolonged enhancement in MRL imaging in normal and inflamed lymph nodes. LEVEL OF
EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:238-245.
PMID- 28419614
TI - Prospective comparison of biphasic contrast-enhanced CT, volume perfusion CT, and
3 Tesla MRI with diffusion-weighted imaging for insulinoma detection.
AB - PURPOSE: To evaluate the diagnostic performance of biphasic contrast-enhanced CT
(CECT), volume perfusion CT (VPCT) and 3 Tesla MRI with diffusion-weighted
imaging (DWI), in patients with clinically suspected insulinomas. MATERIALS AND
METHODS: This prospective study was approved by the institutional review board.
Sixty-four patients with clinically suspected insulinomas underwent biphasic
CECT, VPCT, and 3T MR with DWI. Two radiologists independently determined the
presence/absence of tumor using a 5-scale confidence level. Conspicuity of the
lesion and clarity of tumor-to-pancreatic duct distance were graded. Receiver
operating characteristic analysis was performed to compare diagnostic
performance. RESULTS: Forty-seven patients were tumor positive, with 51 tumors.
The differences between the areas under the curve values for tumor detection were
as follows: 0.715 (CECT), 0.903 (VPCT), 0.832 (MRI without DWI) and 0.955 (MRI
with DWI) for reader 1, and 0.738 (CECT), 0.895 (VPCT), 0.841 (MRI without DWI),
and 0.956 (MRI with DWI) for reader 2. MRI with DWI and VPCT were significantly
more accurate than CECT for insulinoma detection (P = 0.01 and 0.02 for reader 1,
and P = 0.01 and 0.03 for reader 2). Lesion conspicuity was better on MRI
compared with VPCT (P = 0.01), and both were better than CECT (both P < 0.01).
Tumor-to-pancreatic duct distance was better appreciated on MRI, compared with
CECT and VPCT (both P < 0.01). The weighted k values indicate good to excellent
agreement between observers for determining tumor presence/absence (k = 0.64
0.84). CONCLUSION: The 3T MRI with DWI and VPCT are significantly more accurate
than CECT for insulinoma detection. MRI demonstrates higher tumor conspicuity and
is superior in depicting the tumor-to-duct distance. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1648-1655.
PMID- 28419615
TI - Involvement of herpes simplex virus type 1 UL13 protein kinase in induction of
SOCS genes, the negative regulators of cytokine signaling.
AB - The suppressor of cytokine signaling (SOCS) family has eight members and
suppresses various cytokine signaling pathways, including IFN signaling.
Therefore, some viruses have evolved molecular mechanisms for inducing SOCS
proteins and thus escaping host immunity. Herpes simplex virus type 1 (HSV-1) has
a mechanism for escaping from type I IFN by induction of both SOCS1 and SOCS3. In
this study, expression of the eight members of the SOCS family stimulated by HSV
1 infection was comparatively analyzed by qRT-PCR. It was found that SOCS1 and
SOCS3 are induced by HSV-1-infection at 4 hr post infection. However, such
induction was not observed in UL13 deficient virus-infected cells, suggesting
that UL13 protein kinase participates in induction of both genes. The
transcription factor Sp1-binding sites of SOCS3 promoter/enhancer region were
identified as the regulatory elements for induction of SOCS3 in HSV-1 infected
cells. Accumulation of activated Sp1 was detectable in the nuclei of HSV-1
infected cells before induction of SOCS3. Taken together, these results suggest
that HSV-1 has a potent mechanism for escaping from the IFN system.
PMID- 28419616
TI - The provision of pediatric cardiac anesthesia services in Germany: current status
of structural and personnel organization.
AB - BACKGROUND: Anesthesia for pediatric cardiac surgery requires a high level of
expert knowledge. There are currently no recommendations and standards for
anesthetic management for congenital cardiac surgery in Germany. AIM: The aim of
the present study was to assess the current status of structural and personnel
anesthetic standards at pediatric cardiac surgery centers in Germany. METHODS:
All cardiac surgical centers in Germany were reviewed for an active program for
congenital heart surgery. Centers with an active program were invited to respond
to an online survey. The questionnaire containing 55 items in 16 categories
assessed current practice in pediatric cardiac anesthesia. RESULTS: An active
program for pediatric cardiac surgery was identified at 27 centers. The response
rate to the survey was 96.3%. A specialized group of anesthesiologists for
pediatric cardiac anesthesia was reported from 26 centers (92.3%). The mean size
of this group was 4.8 anesthesiologists per center. However, the annual case load
of centers and relative annual case load per specialized anesthesiologist varied
considerably between 12.5 and 250. Nonanesthesiologists performed sedation and
general anesthesia for diagnostic and therapeutic interventions outside the
operating theater in children with congenital heart diseases in 24 centers (77%).
Although special equipment, for example, pediatric TEE, near-infrared
spectroscopy, and devices for mechanical auto transfusion were available in most
centers, their routine use was not always part of standard operating procedures.
The proposal for mean adequate training in pediatric cardiac anesthesia as
estimated by the participating centers was 10.8 months. CONCLUSION: The present
study represents the current structural situation for anesthesia at German
pediatric cardiac surgery centers.
PMID- 28419617
TI - Behavioural addiction and substance addiction should be defined by their
similarities not their dissimilarities.
PMID- 28419618
TI - Correspondence.
PMID- 28419619
TI - Palladium-Catalyzed Enantioselective Alkoxycarbonylation of Propargylic
Carbonates with (R)- or (S)-3,4,5-(MeO)3 -MeOBIPHEP.
AB - (R)- and (S)-3,4,5-(MeO)3 -MeOBIPHEP have been identified as the efficient chiral
ligands for the palladium-catalyzed highly enantioselective synthesis of 2,3
allenoates from different types of easily available racemic propargylic
carbonates with 90-98 % ee and decent yields. The potential of the products was
demonstrated with high chirality transfer efficiency.
PMID- 28419620
TI - Comparison of Emergency Department Patients to Inpatients Receiving a Pulmonary
Embolism Response Team (PERT) Activation.
AB - OBJECTIVES: The development of pulmonary embolism response teams (PERTs) has been
widely adopted nationally with the goal of providing multidisciplinary care to
patients with high-risk PE. Most PERT activations originate from the emergency
department (ED), while others are from the intensive care unit (ICU) or inpatient
floors. It is unclear if ED PERT activations differ from non-ED PERT activation
in terms of presentation, management, and outcome. METHODS: We enrolled a
consecutive cohort of patients for whom PERT was activated at an urban academic
medical center. We compared three groups of PERT activations based on whether the
activation originated from the ED, ICU, or a non-ICU inpatient floor. We compared
these groups in terms of the proportion of PERT activations that occurred during
day, evening, or weekend hours and the proportion of confirmed PE. We also
compared PE severity, treatment, and outcomes across locations. We tested
differences using chi-square tests, with a two-tailed p-value of <0.05 considered
statistically significant. RESULTS: We enrolled 561 patients, of whom 449 (79.5%)
had confirmed PE. The mean +/- SD age of patients with confirmed PE was 61 +/- 17
years, and 300 (53.5%) were male. Activations from the ED (n = 283, 88.4%) or
floor (n = 100, 74.6%) were more likely to be for confirmed PE than activations
from the ICU (n = 63, 58.9%; p < 0.0001). There was a statistical difference in
the time of day of PERT activation with the ED having more activations during
night hours than the ICU or floors (p = 0.004). Most activations for confirmed,
massive PE originated from the ICU (n = 41, 65.1%), followed by the ED (n = 82,
29%) and inpatient floors (n = 22, 22%; p < 0.0001). Most activations from the ED
(n = 155, 54.8%) and floors (n = 55, 55%) were for submassive PE. The use of
thrombolysis or thrombectomy was more common among ICU patients (n = 18, 33.3%),
followed by ED patients (n = 53, 19.6%) and then floor patients (n = 8, 8.2%).
Mortality and major bleeding events were most common among ICU patients and
similar among ED and floor patients. CONCLUSIONS: Pulmonary embolism response
team activations from different clinical locations differ in terms of patient
presentation, PE confirmation, treatments, and outcomes. PERTs should be
customized to support the different needs of each clinical area.
PMID- 28419621
TI - The feasibility, acceptability, and outcomes of PRIME-D: A novel mobile
intervention treatment for depression.
AB - BACKGROUND: Despite decades of research and development, depression has risen
from the fifth to the leading cause of disability in the United States. Barriers
to progress in the field are (1) poor access to high-quality care; (2) limited
mental health workforce; and (3) few providers trained in the delivery of
evidence-based treatments (EBTs). Although mobile platforms are being developed
to give consumers greater access to high-quality care, too often these tools do
not have empirical support for their effectiveness. In this study, we evaluated
PRIME-D, a mobile app intervention that uses social networking, goal setting, and
a mental health coach to deliver text-based, EBT's to treat mood symptoms and
functioning in adults with depression. METHODS: Thirty-six adults with depression
remotely participated in PRIME-D over an 8-week period with a 4-week follow-up,
with 83% retained over the 12-week course of thestudy. RESULTS: On average,
participants logged into the app 5 days/week. Depression scores (PHQ-9)
significantly improved over time (over 50% reduction), with coach interactions
enhancing these effects. Mood-related disability (Sheehan Disability Scale (SDS))
also significantly decreased over time with participants no longer being impaired
by their mood symptoms. Overall use of PRIME-D predicted greater gains in
functioning. Improvements in mood and functioning were sustained over the 4-week
follow-up. CONCLUSIONS: Results suggest that PRIME-D is a feasible, acceptable,
and effective intervention for adults with depression and that a mobile service
delivery model may address the serious public health problem of poor access to
high-quality mental health care.
PMID- 28419622
TI - Quantitative depth resolved microcirculation imaging with optical coherence
tomography angiography (Part Iota): Blood flow velocity imaging.
AB - The research goal of the microvascular network imaging with optical coherence
tomography (OCT) angiography is to achieve depth resolved blood flow and vessel
imaging in vivo in the clinical management of patents. In this review, we review
the main phenomena that have been explored in OCT to image the blood flow
velocity vector and the vessels of the microcirculation within living tissues.
Parameters that limit the accurate measurements of blood flow velocity are then
condisered. Finally, initial Clinic diagnosis applications of and future
developments are discussed. This article is protected by copyright. All rights
reserved.
PMID- 28419623
TI - Cognitive component of psychomotor retardation in unipolar and bipolar
depression: Is verbal fluency a relevant marker? Impact of repetitive
transcranial stimulation.
AB - AIMS: In the literature, psychomotor retardation (PMR) is increasingly
highlighted as a relevant marker for depression. Currently, we chose to focus on
the fluency capacities as an evaluation of the frontal lobes functioning to reach
a better understanding of cognitive and neurobiological mechanisms involved in
PMR in depression. The aims of this study were: (i) to explore the cognitive
component of PMR through the analysis of verbal fluency (VF) performance in
unipolar and bipolar depression; and (ii) to examine whether a repetitive
transcranial magnetic stimulation treatment could improve concomitantly the PMR
and VF capacities, as a relevant marker characteristic of the cognitive component
of PMR. METHODS: Fifteen unipolar and 15 bipolar patients were compared to 15
healthy adults. Before treatment, the results showed VF deficits, particularly
marked in the bipolar group. The investigation of the interplay between PMR, VF
performance, Montgomery-Asberg Depression Rating Scale scores, and Montreal
Cognitive Assessment scores showed that the deficits in these various dimensions
were not homogeneous. RESULTS: The absence of correlation between the psychomotor
retardation scale (the French Retardation Rating Scale for Depression) and VF,
and the correlation with MoCA raise the hypothesis of a more global cognitive
impairment associated with PMR in the BD group. The repetitive transcranial
magnetic stimulation treatment had a positive impact on depression, PMR, and
fluency scores. CONCLUSION: Correlations between the Retardation Rating Scale for
Depression and VF performances appeared after treatment, showing the cognitive
role of psychomotor functioning in depression. Further analyses, including other
cognitive measures in an objective evaluation of PMR, are required for a better
understanding of these complex relationships.
PMID- 28419624
TI - The effect of single oral doses of duloxetine, reboxetine, and midodrine on the
urethral pressure in healthy female subjects, using urethral pressure
reflectometry.
AB - AIMS: To evaluate the effect on urethral pressure of reference drugs known to
reduce stress urinary incontinence symptoms by different effect size and
mechanisms of action on urethral musculature under four test conditions in
healthy female subjects using urethral pressure reflectometry. METHODS: Healthy
females aged 18-55 years were recruited by advertising for this phase 1, single
site, placebo-controlled, randomized, four-period, crossover study. The
interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg
Reboxetine, and placebo. The endpoints were the opening urethral pressure
measured in each period at four time points (predose and 2, 5.5, and 9 h after
dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24
completed the study. The opening urethral pressure was higher in all measurements
with filled bladder compared with empty bladder, and during squeezing compared to
the resting condition. All three drugs increased the opening urethral pressure
during all four conditions with a ranking of their effect on urethral pressure
matching their reported clinical effect (difference vs. placebo at their reported
time of peak plasma concentrations [Tmax ] during resting with filled bladder:
Midodrine 9.3 cmH2 O [95%CI 3.0, 15.5], Duloxetine 24.2 cmH2 O [95%CI 17.9,
30.5], and Reboxetine 44.9 cmH2 O [95% CI 40.2, 52.8] cmH2 O). CONCLUSIONS:
Urethral pressure reflectometry is capable of detecting drug-induced changes in
urethral tone in various conditions. The magnitude of drug-induced changes by the
test drugs seems to match their clinical profile and differences in mode of
action.
PMID- 28419625
TI - Meta-analysis of interventions for posttraumatic stress disorder and depression
in adult survivors of mass violence in low- and middle-income countries.
AB - BACKGROUND: Most survivors of mass violence live in low- and middle-income
countries (LMICs). We conducted a meta-analysis of randomized controlled
psychotherapy trials for adult posttraumatic stress disorder (PTSD) and/or
depression in LMICs. METHODS: We included 18 clinical trials (3,058
participants), in which 25 and 18 treatment arms measured symptoms of PTSD and
depression, respectively. RESULTS: Active treatments for PTSD yielded a large
aggregated pre-post effect size (g = 1.29; 95% CI = [0.99; 1.59]) and a small to
medium effect size at posttreatment when compared to control conditions (g =
0.39; 95% CI = [0.24; 0.55]). Effect sizes were similar for pretreatment versus
follow-up (g = 1.75; 95% CI = [1.17; 2.32]) and in comparison to waitlist at
follow-up (g = 0.93; 95% CI = [0.56; 1.31]). Active treatments for depression
produced large pre-post (g = 1.28; 95% CI = [0.96; 1.61]) and controlled effect
sizes (posttreatment, comparison to control conditions, g = 0.86; 95% CI = [0.54;
1.18]). CONCLUSIONS: Our findings suggest that psychological interventions can
effectively reduce symptoms of PTSD and depression in LMICs. Future research
needs to focus on cost-effective interventions that are likely to be disseminated
to the large numbers of war survivors in LMICs.
PMID- 28419626
TI - Influence of job demands and job control on work-life balance among Taiwanese
nurses.
AB - AIM: This study investigated the extent to which the job demands and job control
of nurses were related to their work-life balance. BACKGROUND: The inability to
achieve work-life balance is one of the major reasons for the declining retention
rate among nurses. Job demands and job control are two major work domain factors
that can have a significant influence on the work-life balance of nurses. METHOD:
The study measured the job demands, job control and work-life balance of 2040
nurses in eight private hospitals in Taiwan in 2013. RESULTS: Job demands and job
control significantly predicted all the dimensions of work-life balance. Job
demands increased the level of work-life imbalance among nurses. While job
control showed positive effects on work/personal life enhancement, it was found
to increase both work interference with personal life and personal life
interference with work. CONCLUSION: Reducing the level of job demands
(particularly for psychological demands) between family and career development
and maintaining a proper level of job control are essential to the work-life
balance of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Flexible work practices
and team-based management could be considered by nursing management to lessen job
demand pressure and to facilitate job engagement and participation among nurses,
thus promoting a better balance between work and personal life.
PMID- 28419627
TI - Instantaneous Conversion of [11 C]CO2 to [11 C]CO via Fluoride-Activated Disilane
Species.
AB - The development of a fast and novel methodology to generate carbon-11 carbon
monoxide ([11 C]CO) from cyclotron-produced carbon-11 carbon dioxide ([11 C]CO2 )
mediated by a fluoride-activated disilane species is described. This methodology
allows up to 74 % conversion of [11 C]CO2 to [11 C]CO using commercially
available reagents, readily available laboratory equipment and mild reaction
conditions (room temperature). As proof of utility, radiochemically pure
[carbonyl-11 C]N-benzylbenzamide was successfully synthesized from produced [11
C]CO in up to 74 % radiochemical yield (RCY) and >99 % radiochemical purity (RCP)
in <=10 min from end of [11 C]CO2 delivery.
PMID- 28419628
TI - HLA-HD: An accurate HLA typing algorithm for next-generation sequencing data.
AB - The accurate typing of human leukocyte antigen (HLA) alleles is critical for a
variety of medical applications, such as genomic studies of multifactorial
diseases, including immune system and inflammation-related disorders, and donor
selection in organ transplantation and regenerative medicine. Here, we developed
a new algorithm for determining HLA alleles using next-generation sequencing
(NGS) results. The method consists of constructing an extensive dictionary of HLA
alleles, precise mapping of the NGS reads, and calculating a score based on
weighted read counts to select the most suitable pair of alleles. The developed
algorithm compares the score of all allele pairs, taking into account variation
not only in the domain for antigen presentation (G-DOMAIN), but also outside this
domain. Using this method, HLA alleles could be determined with 6-digit
precision. We showed that our method was more accurate than other NGS-based
methods and revealed limitations of the conventional HLA typing technologies.
Furthermore, we determined the complete genomic sequence of an HLA-A-like
pseudogene when we assembled NGS reads that had caused arguable typing, and found
its identity with HLA-Y*02:01. The accuracy of the HLA-A allele typing was
improved after the HLA-Y*02:01 sequence was included in the HLA allele
dictionary.
PMID- 28419630
TI - Correction.
PMID- 28419629
TI - Motivational and behavioural models of change: A longitudinal analysis of change
among men with chronic haemophilia-related joint pain.
AB - BACKGROUND: Motivational and behavioural models of adjustment to chronic pain
make different predictions about change processes, which can be tested in
longitudinal analyses. METHODS: We examined changes in motivation, coping and
acceptance among 78 men with chronic haemophilia-related joint pain. Using cross
lagged regression analyses of changes from baseline to 6 months as predictors of
changes from 6 to 12 months, with supplementary structural equation modelling, we
tested two models in which motivational changes influence behavioural changes,
and one in which behavioural changes influence motivational changes. RESULTS:
Changes in motivation to self-manage pain influenced later changes in pain
coping, consistent with the motivational model of pain self-management, and also
influenced later changes in activity engagement, the behavioural component of
pain acceptance. Changes in activity engagement influenced later changes in pain
willingness, consistent with the behavioural model of pain acceptance.
CONCLUSIONS: Based on the findings, a combined model of changes in pain self
management and acceptance is proposed, which could guide combined interventions
based on theories of motivation, coping and acceptance in chronic pain.
SIGNIFICANCE: This study adds longitudinal evidence about sequential change
processes; a test of the motivational model of pain self-management; and tests of
behavioural versus motivational models of pain acceptance.
PMID- 28419631
TI - TgPL2, a patatin-like phospholipase domain-containing protein, is involved in the
maintenance of apicoplast lipids homeostasis in Toxoplasma.
AB - Patatin-like phospholipases are involved in numerous cellular functions,
including lipid metabolism and membranes remodeling. The patatin-like catalytic
domain, whose phospholipase activity relies on a serine-aspartate dyad and an
anion binding box, is widely spread among prokaryotes and eukaryotes. We describe
TgPL2, a novel patatin-like phospholipase domain-containing protein from the
parasitic protist Toxoplasma gondii. TgPL2 is a large protein, in which the key
motifs for enzymatic activity are conserved in the patatin-like domain. Using
immunofluorescence assays and immunoelectron microscopy analysis, we have shown
that TgPL2 localizes to the apicoplast, a non-photosynthetic plastid found in
most apicomplexan parasites. This plastid hosts several important biosynthetic
pathways, which makes it an attractive organelle for identifying new potential
drug targets. We thus addressed TgPL2 function by generating a conditional
knockdown mutant and demonstrated it has an essential contribution for
maintaining the integrity of the plastid. In absence of TgPL2, the organelle is
rapidly lost and remaining apicoplasts appear enlarged, with an abnormal
accumulation of membranous structures, suggesting a defect in lipids homeostasis.
More precisely, analyses of lipid content upon TgPL2 depletion suggest this
protein is important for maintaining levels of apicoplast-generated fatty acids,
and also regulating phosphatidylcholine and lysophosphatidylcholine levels in the
parasite.
PMID- 28419632
TI - Factors influencing beliefs about intimate partner violence among adults in South
Korea.
AB - OBJECTIVES: This study aimed to identify factors influencing beliefs about
intimate partner violence among Korean adults. DESIGN AND SAMPLE: This is a cross
sectional descriptive study that analyzed data from 466 adults. MEASURES: Beliefs
about intimate partner violence were measured using a self-report questionnaire
with a total of 28 items consisting of four subscales: perpetrator's
justification for beating women, blaming women for violence against them,
perpetrator's responsibility for violence, and giving help to victims. RESULTS:
Men and women had significantly different beliefs about intimate partner violence
(t = -7.19, p < .001). Some characteristics were identified that led to unhealthy
beliefs about intimate partner violence. Four variables-gender, age, educational
level, and witnessing parental violence-had an explanatory power of 20% with
regard to beliefs about IPV (F = 10.50, p = .000). CONCLUSIONS: In South Korea,
men, older individuals, and those with less formal education or who have
witnessed parental violence need education to foster healthier beliefs about
intimate partner violence. Nurses can play a vital role in efforts to decrease
intimate partner violence.
PMID- 28419633
TI - BK virus in solid organ transplantation: Pretransplant screening of recipients
and risk factors for disease.
PMID- 28419634
TI - Contrast-Enhanced Ultrasound and Elastography Imaging of the Neonatal Brain: A
Review.
AB - Neonates presenting with neurologic symptoms require rapid, noninvasive imaging
with high spatial resolution and tissue contrast. Magnetic resonance imaging
(MRI) is currently the most sensitive and specific imaging modality for
evaluation of neurological pathology. This modality does come with several
challenges in the neonatal population, namely, the need to transport a possibly
critically sick neonate to the MRI suite and the necessity of the neonate to
remain still for a significant length of time, occasionally requiring sedation.
Cranial ultrasound has provided radiologists and clinicians with an invaluable
imaging modality that allows of rapid, bedside point of care evaluation without
ionizing radiation. The major drawback of cranial ultrasound is its lower
sensitivity and specificity for subtle/early lesions. Contrast-enhanced
ultrasound (CEUS) and elastography have the potential to improve sensitivity and
specificity for a variety of neuropathology but also expand the indications for
cranial ultrasound. Goal of this paper is to present and discuss CEUS and
elastography for neonatal brain imaging.
PMID- 28419635
TI - Canine histiocytic sarcoma presenting as a target lesion on brain magnetic
resonance imaging and as a solitary pulmonary mass.
AB - A 6-year-old spayed female miniature schnauzer presented with generalized
seizures and progressive multifocal intracranial neurologic disease. Thoracic
radiographs and computed tomography (CT) revealed a large solitary pulmonary mass
within the right cranial lung lobe. On brain magnetic resonance imaging (MRI), a
solitary intraparenchymal mass within the left piriform lobe had a "target"
appearance on both pre- and postcontrast sequences. Cerebrospinal fluid was
unremarkable and histopathology indicated both masses represented histiocytic
sarcoma. This case represents an uncommonly reported MRI appearance of
histiocytic sarcoma in the canine brain and a large, solitary-appearing pulmonary
histiocytic sarcoma in the same dog.
PMID- 28419636
TI - A case of solitary pulmonary capillary hemangioma indicating true gross
appearance.
PMID- 28419637
TI - Self-reported prevalence, description and management of pain in adults with
haemophilia: methods, demographics and results from the Pain, Functional
Impairment, and Quality of life (P-FiQ) study.
AB - INTRODUCTION: Haemophilia is characterized by frequent haemarthrosis, leading to
acute/chronic joint pain. AIM: To assess self-reported prevalence, description
and management of pain in adult males with mild-to-severe haemophilia and history
of joint pain/bleeding. METHODS: Participants completed a pain survey and five
patient-reported outcome instruments assessing pain, functional impairment and
health-related quality of life (HRQoL). RESULTS: Of 381 participants enrolled,
median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65%
were overweight/obese. Many (56%) were not receiving routine infusions; 30% never
received routine infusions. During the prior 6 months, 20% experienced acute
pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both
acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed
(30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual
analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities
List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during
the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti
inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice
(65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common
opioid for both acute/chronic pain (30%); other long-acting opioids were
infrequently used specifically for chronic but not acute pain (morphine, 7%;
methadone, 6%; fentanyl patch, 2%). CONCLUSION: Patients with chronic pain,
particularly those with both acute/chronic pain, frequently experience
psychological issues, functional disability and reduced HRQoL. Treatment
strategies for acute pain (e.g. routine infusions to prevent bleeding) and for
chronic pain (e.g. long-acting opioids) may be underused.
PMID- 28419638
TI - Diffusion tensor imaging tractography study in bipolar disorder patients compared
to first-degree relatives and healthy controls.
AB - AIM: We aimed to compare white matter structural changes in specific tracts by
diffusion tensor imaging (DTI) tractography in patients with bipolar disorder
(BD) I, non-ill first-degree relatives (FDR) of the patients, and healthy
controls (HC). METHODS: In a cross-sectional study, we studied right-handed
subjects consisting of 16 euthymic BD I patients, 15 FDR, and 15 HC. The anterior
thalamic radiation, uncinate fasciculus, corpus callosum, and cingulum bundle
were reconstructed by DTI tractography. Mean fractional anisotropy (FA) and
apparent diffusion coefficient (ADC) values were compared for group differences
followed by post-hoc analysis. RESULTS: The three groups did not differ in terms
of sociodemographic variables. There were significant group differences in the FA
values among the BD I patients, their FDR, and the HC for the corpus callosum,
the dorsal part of the right cingulum bundle, the hippocampal part of the
cingulum bundle bilaterally, and the uncinate fasciculus (P < 0.001). The FA
values in the patients were significantly lower than in controls, and FDR also
showed similar differences; however, they were smaller than those in patients. No
significant difference was found between the groups for FA values of the dorsal
part of the left cingulum bundle and anterior thalamic radiation. Significant
differences were present for ADC values among the groups for the corpus callosum,
the dorsal and hippocampal parts of the cingulum, anterior thalamic radiation,
and uncinate fasciculus bilaterally (P < 0.01). The FA and ADC values did not
correlate significantly with age or any clinical variables. CONCLUSION: These
findings suggest that BD patients and their FDR show alterations in
microstructural integrity of white matter tracts, compared to the healthy
population.
PMID- 28419639
TI - Differences in intraoperative hemodynamics between spinal and general anesthesia
in infants undergoing pyloromyotomy.
AB - BACKGROUND: Hypotension and bradycardia are known side effects of spinal
anesthesia in pregnant women undergoing cesarean section and adults undergoing
other surgical procedures. Whether children experience similar hemodynamic
changes is unclear. AIMS: The purpose of this study is to evaluate hemodynamic
effects of spinal anesthesia compared to general anesthesia in a cohort of
healthy infants. METHODS: The University of Vermont Medical Center almost
exclusively used spinal anesthesia for infant pyloromyotomy surgery between 2008
and 2013, while Columbia University Medical Center relied on general anesthesia.
The primary outcome assessed was the percentage change in intraoperative heart
rate and blood pressure (systolic [SBP] and mean [MAP] blood pressure) from
baseline. Analysis was performed using t-tests for continuous variables, followed
by linear regression to account for differences in demographic and clinical
covariates. RESULTS: The study sample consisted of 51 infants with spinal
anesthesia at the University of Vermont and 52 infants with general anesthesia at
Columbia University. The decrease from baseline for mean intraoperative SBP was
8.2 +/- 16.8% for spinal anesthesia and -24.2 +/- 17.2% for general anesthesia
(difference between means: 16.2% [95% confidence interval (CI), 9.5-22.9]), while
the decrease from baseline for mean intraoperative MAP was -16.3 +/- 19.9% for
spinal anesthesia and -24.6 +/- 19.3% for general anesthesia (difference between
means: 8.4% [95% CI, 0.8-16]). Spinal anesthesia patients also had smaller drops
in minimum intraoperative MAP and SBP. These blood pressure differences persisted
even after adjusting for covariates. No differences in heart rate were seen
between spinal and general anesthesia. DISCUSSION: Our findings show that spinal
anesthesia performed in healthy infants undergoing pyloromyotomy results in
reduced intraoperative blood pressure changes from baseline, significantly higher
blood pressure readings, and no increased bradycardia compared to general
anesthesia. Further research is needed to assess whether any clinical impact of
these hemodynamic differences between spinal and general anesthesia exists.
PMID- 28419640
TI - Relationships between dispositional mindfulness, self-acceptance, perceived
stress, and psychological symptoms in advanced gastrointestinal cancer patients.
AB - OBJECTIVE: Previous studies have shown that dispositional mindfulness is
associated with less psychological symptoms in cancer patients. The present study
investigated how dispositional mindfulness is related to psychological symptoms
in advanced gastrointestinal cancer patients by considering the roles of self
acceptance and perceived stress. METHODS: A total of 176 patients with advanced
gastrointestinal cancer were recruited to complete a series of questionnaires
including Mindfulness Attention Awareness Scale, Self-acceptance Questionnaire,
Chinese Perceived Stress Scale, and General Health Questionnaire. RESULTS:
Results showed that the proposed model fitted the data very well (chi2 = 7.564,
df = 7, P = .364, chi2 /df = 1.094, Goodness of Fit Index (GFI) = 0.986,
Comparative Fit Index (CFI) = 0.998, Tucker Lewis Index (TLI) = 0.995, Root Mean
Square Error of Approximation (RMSEA) = 0.023). Further analyses revealed that,
self-acceptance and perceived stress mediated the relation between dispositional
mindfulness and psychological symptoms (indirect effect = -0.052, 95% confidence
interval = -0.087 ~ -0.024), while self-acceptance also mediated the relation
between dispositional mindfulness and perceived stress (indirect effect = -0.154,
95% confidence interval = -0.261 ~ -0.079). CONCLUSIONS: Self-acceptance and
perceived stress played critical roles in the relation between dispositional
mindfulness and psychological symptoms. Limitations, clinical implications, and
directions for future research were discussed.
PMID- 28419641
TI - Neural correlates of experimental trauma memory retrieval.
AB - OBJECTIVES: Traumatic memories such as intrusions and flashbacks play a major
role in the development and maintenance of post-traumatic stress disorder (PTSD).
A thorough understanding of the neural mechanisms underlying traumatic memories
is indispensable for precise diagnosis, for personalized treatment and
prevention. In particular, the identification of early neural predictor variables
for intrusion development shortly after trauma exposure requires detailed
investigation. EXPERIMENTAL DESIGN: Here, we examined the neural correlates of
early experimental trauma memory retrieval in a traumatic film paradigm in 42
young healthy females, using both implicit and explicit retrieval tasks.
PRINCIPAL OBSERVATIONS: We show that implicit experimental trauma retrieval
specifically involved the retrosplenial cortex and the anterior cingulate cortex
(ACC), while both retrieval tasks resulted in trauma-related activity in the
posterior cingulate cortex (PCC) and the precuneus. Importantly, neural activity
early after experimental trauma exposure predicted later intrusion development,
with independent contributions from activity in the retrosplenial cortex
(implicit retrieval) and the PCC (explicit retrieval). Additional analyses
revealed a stronger connectivity between the bilateral amygdala and the
supplementary motor area, precentral and paracentral lobule for the control group
compared to the experimental trauma group. CONCLUSIONS: Our study gives new
insights in the neural correlates of experimental trauma memory retrieval and
their predictive value for subsequent symptom development. Our results could
provide the basis for personalized early treatment and prevention of PTSD. Hum
Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419642
TI - Nicotine-induced molecular alterations are modulated by GABAB receptor activity.
AB - It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward
effect; nevertheless, the mechanism implicated is not well known. In this regard,
we evaluated the involvement of GABAB receptors on the behavioral, neurochemical,
biochemical and molecular alterations associated with the rewarding effects
induced by NIC in mice, from a pharmacological and genetic approach. NIC-induced
rewarding properties (0.5 mg/kg, subcutaneously, sc) were evaluated by
conditioned place preference (CPP) paradigm. CPP has three phases:
preconditioning, conditioning and postconditioning. GABAB receptor antagonist 2
hydroxysaclofen (0.25, 0.5 and 1 mg/kg; intraperitoneally, ip) or the GABAB
receptor agonist baclofen (3 mg/kg; ip) was injected before NIC during the
conditioning phase. GABAB1 knockout (GABAB1 KO) mice received NIC during the
conditioning phase. Vehicle and wild-type controls were employed. Neurochemical
(dopamine, serotonin and their metabolites), biochemical (nicotinic receptor
alpha4beta2, alpha4beta2nAChRs) and molecular (c-Fos) alterations induced by NIC
were analyzed after the postconditioning phase by high-performance liquid
chromatography (HPLC), receptor-ligand binding assays and immunohistochemistry,
respectively, in nucleus accumbens (Acb), prefrontal cortex (PFC) and ventral
tegmental area (VTA). NIC induced rewarding effects in the CPP paradigm and
increased dopamine levels in Acb and PFC, alpha4beta2nAChRs density in VTA and c
Fos expression in Acb shell (AcbSh), VTA and PFC. We showed that behavioral,
neurochemical, biochemical and molecular alterations induced by NIC were
prevented by baclofen. However, in 2-hydroxysaclofen pretreated and GABAB1 KO
mice, these alterations were potentiated, suggesting that GABAB receptor activity
is necessary to control alterations induced by NIC-induced rewarding effects.
Therefore, the present findings provided important contributions to the
mechanisms implicated in NIC-induced rewarding effects.
PMID- 28419643
TI - Post-lunch triglyceridaemia associates with HDLc and insulin resistance in
fasting normotriglyceridaemic menopausal women.
AB - OBJECTIVES: Post-prandial hypertriglyceridaemia (P-HTG) is associated with
cardiovascular disease. This association is of paramount importance during
menopause, which is also related to reduced high-density lipoprotein-cholesterol
(HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing
tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at
fasting and adhered to a Mediterranean-style eating pattern. METHODS: We
performed oral fat loading tests (OFLT) in combination with self-measurements of
diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women.
TG levels >220 mg dL-1 at any given time during the OFLT served as diagnostic
criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the
best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to
classify these women as having P-HTG according to the OFLT. Insulin resistance
was defined as the upper tertile of the homeostatic model assessment of insulin
resistance. RESULTS: We found that, despite having normal fasting TG levels, P
HTG was highly prevalent (approximately 40%). Moreover, self-assessed 3-h post
lunch TG levels >165 mg dL-1 increased the odds of having hypo-HDL
cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin
resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women
adhering to a Mediterranean eating pattern having their highest energy intake at
lunch. CONCLUSIONS: Self-assessed 3-h post-lunch TG can be used to study post
prandial TG metabolism in Southern European menopausal women who are
normotriglyceridaemic at fasting. Characterising an individual's post-prandial
response may help menopausal women to evaluate their risk of cardiovascular
disease.
PMID- 28419644
TI - Diffusion-weighted imaging of hyperpolarized [13 C]urea in mouse liver.
AB - PURPOSE: To compare the apparent diffusion coefficient (ADC) of hyperpolarized
(HP) [13 C,15 N]urea to the ADC of endogenous water in healthy and fibrotic mouse
liver. MATERIALS AND METHODS: ADC measurements for water and [13 C]urea were made
in agarose phantoms at 14.1T. Next, the ADC of water and injected HP [13 C,15
N]urea were measured in eight CD1 mouse livers before and after induction of
liver fibrosis using CCl4 . Liver fibrosis was quantified pathologically using
the modified Brunt fibrosis score and compared to the measured ADC of water and
urea. RESULTS: In cell-free phantoms with 12.5% agarose, water ADC was nearly
twice the ADC of urea (1.93 * 10-3 mm2 /s vs. 1.00 * 10-3 mm2 /s). The mean ADC
values of water and [13 C,15 N]urea in healthy mouse liver (+/-SD) were nearly
identical [(0.75 +/- 0.11) * 10-3 mm2 /s and (0.75 +/- 0.22) * 10-3 mm2 /s,
respectively]. Mean water and [13 C,15 N]urea ADC values in fibrotic liver (+/
SD) were (0.84 +/- 0.22) * 10-3 mm2 /s and (0.75 +/- 0.15) * 10-3 mm2 /s,
respectively. Neither water nor urea ADCs were statistically different in the
fibrotic livers compared to baseline (P = 0.14 and P = 0.99, respectively). Water
and urea ADCs were positively correlated at baseline (R2 = 0.52 and P = 0.045)
but not in fibrotic livers (R2 = 0.23 and P = 0.23). CONCLUSION: ADC of injected
hyperpolarized urea in healthy liver reflects a smaller change as compared to
free solution than ADC of water. This may reflect differences in cellular
compartmentalization of the two compounds. No significant change in ADC of either
water or urea were observed in relatively mild stages of liver fibrosis. LEVEL OF
EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:141-151.
PMID- 28419645
TI - Diagnostic performance of different imaging modalities in the assessment of
distant metastasis and local recurrence of tumor in patients with non-small cell
lung cancer.
AB - PURPOSE: To compare the diagnostic performance of positron emission tomography
with [18F] fluoro-2-deoxy-glucose (FDG-PET) coregistered with magnetic resonance
imaging (FDG-PET/MRI), MRI with and without diffusion-weighted imaging (DWI), FDG
PET fused with computed tomography (FDG-PET/CT) with brain contrast-enhanced (CE
) MRI, and routine radiological examination for assessment of postoperative
recurrence in nonsmall-cell lung cancer (NSCLC) patients. MATERIALS AND METHODS:
96 consecutive postoperative NSCLC patients (52 men, 44 women; mean age 72 years)
prospectively underwent whole-body 3T MRI with and without DWI; PET/CTs and
routine radiological examinations consisted of CE-brain MRI, whole-body CE-CT,
and bone scintigraphy. The patients were divided into a recurrence (n = 17) and a
nonrecurrence (n = 79) group based on pathological and follow-up examinations.
All coregistered PET/MRIs were generated by proprietary software. The probability
of recurrence was visually assessed on a per-patient basis. Receiver operating
characteristic analyses were used to compare the diagnostic performance of all
methods. Finally, diagnostic capabilities were compared by means of McNemar's
test. RESULTS: Areas under the curves (Azs) were significantly larger for PET/MRI
and whole-body MRI with DWI (Az = 0.99) than for PET/CT (Az = 0.92, P < 0.05) and
conventional radiological examination (Az = 0.91, P < 0.05). Specificity and
accuracy of PET/MRI and MRI with and without DWI were significantly higher than
those of PET/CT (P < 0.05) and routine radiological examination (P < 0.05).
CONCLUSION: Whole-body FDG-PET/MRI and MRI with DWI were found to be more
specific and accurate than FDG-PET/CT and routine radiological examinations for
assessment of recurrence in NSCLC patients, although MRI with and without DWI
demonstrated slightly lower sensitivity than PET/CT. LEVEL OF EVIDENCE: 2
Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1707-1717.
PMID- 28419646
TI - Suvorexant, an orexin/hypocretin receptor antagonist, attenuates motivational and
hedonic properties of cocaine.
AB - Orexins ('hypocretins') are peptides produced by neurons of the hypothalamus that
project to structures implicated in reward and emotion processing. Converging
evidence demonstrates functional roles of orexin signaling in arousal,
sleep/wakefulness and motivated behaviors for natural and drug rewards.
Suvorexant, a dual orexin receptor antagonist, recently received approval from
the US Food and Drug Administration to treat insomnia. In Experiment 1, rats self
administered cocaine under a progressive-ratio schedule of reinforcement and the
effects of suvorexant on motivation to self-administer cocaine were measured. In
Experiment 2, the effects of suvorexant on cocaine reward were assessed by using
a place conditioning paradigm, and 50-kHz ultrasonic vocalizations were also
recorded to track changes in hedonic reactivity to cocaine. To rule out
potentially confounding effects of suvorexant-induced somnolence, locomotor
activity was also measured. In Experiment 3, the effects of suvorexant on cocaine
evoked elevations in ventral striatal dopamine were examined. Data reveal that
suvorexant (i) reduced the number of cocaine infusions earned during progressive
ratio self-administration; (ii) attenuated initial positive hedonic reactivity to
cocaine and prevented cocaine place preference; (iii) did not affect cocaine
induced hyperlocomotion and (iv) reduced cocaine-induced elevations in
extracellular ventral striatal dopamine. The present study examined the
therapeutic potential of suvorexant in rodent models of cocaine use disorder.
These results contribute toward a growing literature supporting therapeutic roles
of orexin receptor antagonists in treating substance use disorders.
PMID- 28419647
TI - A dramatic response to a single dose of infliximab in a patient with prolonged
pustular psoriasis derived from inverse psoriasis.
AB - We report a case of a 25-year-old Chinese man with an exceptionally prolonged
history of pustular psoriasis derived from inverse psoriasis who was unsatisfied
with conventional treatment and was successfully treated with a single dose of
infliximab without noticeable adverse effects. No recurrence or flaring was
observed after 3 months of follow-up. This case illustrates that infliximab may
be an effective and safe therapeutic option for patients with refractory pustular
psoriasis derived from inverse psoriasis.
PMID- 28419648
TI - The role of body image dissatisfaction in the association between treatment
related scarring or disfigurement and psychological distress in adult survivors
of childhood cancer.
AB - OBJECTIVE: To examine the potential mediating role of body image dissatisfaction
on the association between treatment-related scarring/disfigurement and
psychological distress in adult survivors of childhood cancer. METHODS:
Participants included 1714 adult survivors of childhood cancer (mean [SD] age at
evaluation = 32.4 [8.0] years, time since diagnosis = 24.1 [8.1] years) enrolled
in the St. Jude Lifetime Cohort Study. Survivors completed measures of body
image, emotional distress, and posttraumatic stress symptoms (PTSS). Body image
dissatisfaction (BID) was categorized into 2 groups (cancer-related and general)
based on factor analysis. Using causal mediation analysis, we estimated the
proportion of psychological distress associated with treatment-related
scarring/disfigurement that could be eliminated by resolving BID through a
hypothetical intervention. RESULTS: Among survivors with scarring/disfigurement
of the head, a sizable proportion of the relative excess of psychological
distress could be eliminated if BID was successfully treated (males: [cancer
related BID: depression: 63%; anxiety: 100%; PTSS: 52%]; [general BID:
depression: 70%; anxiety: 100%; PTSS: 42%]; females: [cancer-related BID:
depression: 20%; anxiety; 36%; PTSS: 23%]; [general BID: depression: 32%;
anxiety: 87%; PTSS: 38%]). The mediating effect of BID was less pronounced for
the association between scarring/disfigurement of the body and psychological
distress for both males and females. CONCLUSIONS: Body image dissatisfaction
mediates the association treatment-related scarring/disfigurement and
psychological distress among adult survivors of childhood cancer, particularly
among survivors with scarring/disfigurement of the head and male survivors.
Successful treatment of body image dissatisfaction has the potential to eliminate
a substantial proportion of psychological distress related to
scarring/disfigurement among adult survivors of childhood cancer.
PMID- 28419649
TI - A paradigm for examining stress effects on alcohol-motivated behaviors in
participants with alcohol use disorder.
AB - Although epidemiological research has shown an increase in drinking following
stressors and trauma, limited paradigms have been validated to study the
relationship between stress and drinking in the human laboratory. The current
study developed a progressive ratio (PR) operant procedure to examine the effects
of psychosocial stress on alcohol craving and several alcohol-motivated behaviors
in persons with alcohol use disorder. Current heavy, nontreatment-seeking
drinkers (N = 30) were media-recruited and completed a comprehensive assessment
of recent drinking, mood and health. Participants were admitted to the clinical
research unit and underwent 4-day, physician-monitored alcohol abstinence. On
days 4 and 5, participants underwent the Trier Social Stress Test or a neutral
session in random order followed by the alcohol-motivated response (AMR)
procedure in which subjects worked for money or alcohol under a PR operant
procedure. Subjects received earned money vouchers or alcohol at the conclusion
of the session. The Trier Social Stress Test increased alcohol craving and rate
of responding and decreased the number of changeovers between alcohol versus
money reinforcers on the PR schedule. There was a positive relationship between
alcohol craving and drinks earned during the stress session. This novel paradigm
provides an experimental platform to examine motivation to drink without
confounding by actual alcohol ingestion during the work session, thereby setting
the stage for future studies of alcohol interventions.
PMID- 28419651
TI - Reply Letter to "Does motor cortex plasticity depend on the type of mutation in
the LRRK2 gene?"
PMID- 28419650
TI - Cardiovascular safety in refractory incontinent patients with overactive bladder
receiving add-on mirabegron therapy to solifenacin (BESIDE).
AB - AIMS/OBJECTIVES: In the BESIDE study, combination therapy (antimuscarinic
[solifenacin] and beta3 -adrenoceptor agonist [mirabegron]) improved efficacy
over solifenacin monotherapy without exacerbating anticholinergic side effects in
overactive bladder (OAB) patients; however, a potential synergistic effect on the
cardiovascular (CV) system requires investigation. METHODS: OAB patients
remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind
run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5
mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg
for 12 weeks. CV safety assessments included frequency of CV-related treatment
emergent adverse events (TEAEs), change from baseline in vital signs (systolic
blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and
electrocardiogram (ECG) parameters. RESULTS: The frequency of hypertension,
tachycardia and ECG QT prolongation, respectively, was low and comparable across
combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and
solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from
baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination
(0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93
mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28
mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with
the exception of a mean treatment difference of ~1 mm Hg in SBP between
combination and solifenacin monotherapy; SBP was unchanged with combination and
decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG
parameters were generally similar across treatment groups, except for QT interval
corrected using Fridericia's formula, which was higher with solifenacin 10 mg
(3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77
mseconds). CONCLUSION: The comparable frequency of CV-related TEAEs, changes in
vital signs and ECG parameters indicates no synergistic effect on CV safety
outcomes when mirabegron and solifenacin are combined.
PMID- 28419652
TI - Degradation of an Ethylene Carbonate/Diethyl Carbonate Mixture by Using Ionizing
Radiation.
AB - The reactivity of ethylene carbonate (EC) and of a EC/diethyl carbonate (DEC)
mixture was studied under ionizing radiation to mimic the aging phenomena that
occur in lithium-ion batteries. Picosecond-pulse radiolysis experiments showed
that the attachment of the electron to the EC molecule is ultrafast (k(e-EC
+EC)=1.3*109 L mol-1 s-1 at 46 degrees C). This reaction rate is accelerated
by a factor of 5.7 compared with the electron attachment to propylene carbonate,
which implies that the presence of the methyl group significantly slows the
reaction. In a 50:50 EC/DEC mixture, just after the electron pulse the electron
is solvated by a mixture of EC and DEC molecules, but its fast decay is
attributed exclusively to electron attachment to the EC molecule. Stable products
detected after steady-state irradiation were mainly H2 , CH4 , CO, and CO2 . The
evolution of the radiolytic yields with the EC fraction shows that H2 and CH4 did
not exhibit linear behavior, whereas CO and CO2 did. Indeed, H2 and CH4 mainly
arise from the excited state of DEC, the formation of which is significantly
affected by the evolution of the dielectric constant of the mixture and by the
electron attachment to EC. CO formation is mainly due to the reactivity of the EC
molecule, which is not affected in the mixture, as proven by pulse-radiolysis
experiments.
PMID- 28419654
TI - Degradation and metabolism of synthetic plastics and associated products by
Pseudomonas sp.: capabilities and challenges.
AB - Synthetic plastics, which are widely present in materials of everyday use, are
ubiquitous and slowly-degrading polymers in environmental wastes. Of special
interest are the capabilities of microorganisms to accelerate their degradation.
Members of the metabolically diverse genus Pseudomonas are of particular interest
due to their capabilities to degrade and metabolize synthetic plastics.
Pseudomonas species isolated from environmental matrices have been identified to
degrade polyethylene, polypropylene, polyvinyl chloride, polystyrene,
polyurethane, polyethylene terephthalate, polyethylene succinate, polyethylene
glycol and polyvinyl alcohol at varying degrees of efficiency. Here, we present a
review of the current knowledge on the factors that control the ability of
Pseudomonas sp. to process these different plastic polymers and their by
products. These factors include cell surface attachment within biofilms,
catalytic enzymes involved in oxidation or hydrolysis of the plastic polymer,
metabolic pathways responsible for uptake and assimilation of plastic fragments
and chemical factors that are advantageous or inhibitory to the biodegradation
process. We also highlight future research directions required in order to
harness fully the capabilities of Pseudomonas sp. in bioremediation strategies
towards eliminating plastic wastes.
PMID- 28419653
TI - HCV viraemia associates with NK cell activation and dysfunction in antiretroviral
therapy-treated HIV/HCV-co-infected subjects.
AB - The impact of hepatitis C virus (HCV) RNA levels on immune status in chronically
HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy
(ART) remains poorly understood. A total of 78 African American subjects HCV
viraemic/naive to HCV treatment (33 HCV genotype 1 mono-infected, 45 ART-treated
HIV/HCV genotype 1 co-infected) were studied. Clinical and liver enzyme
measurements were performed. Whole blood was analysed for immune subset changes
by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used for same
day constitutive and in vitro Interferon (IFN)-alpha-induced signal transducer
and activator of transcription (STAT) phosphorylation, K562 target cell lysis and
K562 target cell recognition-mediated IFN-gamma production. Statistical analysis
was performed using R (2.5.1) or JMP Pro 11. While both groups did not differ in
the level of liver enzymes, HIV/HCV had higher T-cell activation/exhaustion, and
constitutive STAT-1 phosphorylation compared to HCV. In contrast, CD4+ FoxP3+
CD25+ frequency, IFN-alphaR expression on NK cells, as well as constitutive and
IFN-alpha-induced direct cytotoxicity were lower in HIV/HCV. Linear regression
models further supported these results. Finally, increase in HCV viral load and
CD4+ T-cell count had an opposite effect between the two groups on NK cell
activity and T-cell activation, respectively. HCV viral load in ART-treated
HIV/HCV co-infection was associated with greater immune activation/exhaustion and
NK dysfunction than HCV viral load alone in HCV mono-infection. The more
pronounced immune modulation noted in ART-treated HIV-co-infected/untreated HCV
viraemic subjects may impact HCV disease progression and/or response to
immunotherapy.
PMID- 28419655
TI - Cytokine and adipokine are biofactors can act in blood and colostrum of obese
mothers.
AB - Breast milk contains bioactive components that contribute to newborn development.
However, colostrum may undergo biochemical and immunological changes as a
function of maternal overweight and obesity. To investigate this hypothesis, this
study determined the levels of hormones and immunological markers in the serum
and colostrum of overweight and obese mothers. Colostrum and serum samples were
collected from 15 normoweight, 15 overweight, and 15 obese women for
determination of leptin, adiponectin, cytokines (TNF-alpha, IL-6, IL-10), and C
reactive protein (CRP). Obese mothers exhibited higher levels of serum TNF-alpha,
IL-6, and CRP, serum and colostrum leptin and colostrum adiponectin and lower
levels of serum adiponectin. Leptin levels in maternal serum and colostrum were
positively correlated, as was pre-pregnancy BMI and serum TNF-alpha, IL-6, CRP,
and leptin. Adiponectin levels in colostrum and serum were negatively correlated.
The results suggest that obesity changes hormonal and immunological components of
maternal serum and colostrum. The modifications can have short-term and long-term
effects on newborn development. (c) 2016 BioFactors, 43(2):243-250, 2017.
PMID- 28419656
TI - Cannabis, psychosis and schizophrenia: unravelling a complex interaction.
AB - The relationship between cannabis and psychosis and schizophrenia has tested the
field of addiction for decades, and in some ways serves as measure of our ability
to provide a credible contribution to public health. As cannabis is used widely,
many people are interested in the risks the drug poses to mental health. This
paper focuses upon a seminal study examining this, the trajectory of subsequent
research findings and what this has meant for understanding and communicating
risk factor information. These studies provided evidence of a dose-response
relationship between cannabis and psychosis, and that for those individuals with
schizophrenia cannabis exacerbated their symptoms. The findings fit with a multi
causal model in which vulnerability interacts with a precipitating agent to
produce a disease outcome. Even though this is a common model in epidemiology, it
has proved difficult to communicate it in this case. This may be because at a
population level the increased risk is weak and the vulnerabilities relatively
rare. It may also be because people bring strongly held preconceptions to
interpreting a complex multi-causal phenomenon.
PMID- 28419657
TI - A new approach to clinical research: Integrating clinical care, quality
reporting, and research using a wound care network-based learning healthcare
system.
AB - The disparity between ideal evidence from randomized controlled trials and real
world evidence in medical research has prompted the United States Food and Drug
Administration to consider the use of real-world data to better understand safety
and effectiveness of new devices for a broader patient population and to
prioritize real-world data in regulatory decision making. As the healthcare
system transitions from volume- to value-based care, there is a growing need to
harness the power of real-world data to change the paradigm for wound care
clinical research and enable more generalizable clinical trials. This paper
describes the implementation of a network-based learning healthcare system by a
for-profit consortium of wound care clinics that integrates wound care
management, quality improvement, and comparative effectiveness research, by
harnessing structured real-world data within a purpose-built electronic health
record at the point of care. Centers participating in the consortium submit their
clinical data and quality measures to a qualified clinical data registry for
wound care, enabling benchmarking of their data across this national network. The
common definitional framework of the purpose-built electronic health record and
the 21 wound-specific quality measures help to standardize the potential sources
of bias in real-world data, making the consortium data useful for comparative
effectiveness research. This consortium can transform wound care clinical
research and raise the standards of care, while helping physicians achieve
success with the Merit-Based Incentive Payment System.
PMID- 28419658
TI - Ancestral Haloalkane Dehalogenases Show Robustness and Unique Substrate
Specificity.
AB - Ancestral sequence reconstruction (ASR) represents a powerful approach for
empirical testing structure-function relationships of diverse proteins. We
employed ASR to predict sequences of five ancestral haloalkane dehalogenases
(HLDs) from the HLD-II subfamily. Genes encoding the inferred ancestral sequences
were synthesized and expressed in Escherichia coli, and the resurrected ancestral
enzymes (AncHLD1-5) were experimentally characterized. Strikingly, the ancestral
HLDs exhibited significantly enhanced thermodynamic stability compared to extant
enzymes (DeltaTm up to 24 degrees C), as well as higher specific activities with
preference for short multi-substituted halogenated substrates. Moreover,
multivariate statistical analysis revealed a shift in the substrate specificity
profiles of AncHLD1 and AncHLD2. This is extremely difficult to achieve by
rational protein engineering. The study highlights that ASR is an efficient
approach for the development of novel biocatalysts and robust templates for
directed evolution.
PMID- 28419659
TI - Making visible the politics and ethics of alcohol policy research.
AB - Although research on alcohol policy has produced a huge international literature,
alcohol research and policy itself-its cultural assumptions, methods, politics
and ethics-has rarely been subject to critical analysis. In this article, I
provide an appreciative review of an exception to this trend: Joseph Gusfield's
1981 classic, The Culture of Public Problems: Drinking-Driving and the Symbolic
Order. I first outline Gusfield's argument that the 'problem of drinking-driving'
is constructed as a 'drama of individualism' centring on the 'killer drunk'. The
'culture' of drinking-driving research and policy emphasizes alcohol as the
problem and locates the source of car accidents in the moral failings of the
individual motorist, rather than in social institutions or physical environments.
For Gusfield, this construction of the problem is the outcome of political and
ethical choices rather than of 'objective' conditions. In the second part of the
article, I highlight the book's remarkable foresight in anticipating later trends
in critical policy analysis, and argue that it should be regarded as a
sociological classic and as required reading for those working in alcohol and
indeed other drug policy research. I conclude by arguing that The Culture of
Public Problems remains relevant to those working in alcohol and other drug
policy research, although the reasons for its relevance differ depending on
readers' theoretical commitments.
PMID- 28419660
TI - Acute masseter dystonia in a pediatric patient receiving aripiprazole and
methylphenidate following induction of general anesthesia.
AB - An 11-year-old male receiving aripiprazole, methylphenidate, and clonidine
developed acute masseter dystonia inhibiting tracheal intubation after induction
of general anesthesia with propofol and rocuronium. Following emergence, he had
trismus and jaw discomfort. Psychiatry consultation suspected an acute dystonic
reaction, so diphenhydramine was administered intravenously which resolved
symptoms. We suspect chronic aripiprazole and methylphenidate usage combined with
propofol administration in the short-term absence of methylphenidate made this
patient susceptible to dystonic reactions.
PMID- 28419661
TI - Cognitive behavioural therapy stabilises glycaemic control in adolescents with
type 1 diabetes-Outcomes from a randomised control trial.
AB - BACKGROUND: To compare the impact of cognitive behavioural therapy (CBT) with non
directive supportive counselling (NDC) on glycaemic control and psychological
well-being in adolescents with type 1 diabetes mellitus (T1DM). MATERIALS AND
METHODS: Participants aged 11 to 16 years with T1DM (duration >=1 year) from 4 UK
based paediatric diabetes centres were randomised to receive either 6 weekly
sessions of 1-to-1 CBT (n = 43) or NDC (n = 42), with 2 further sessions at 6 and
12 months. Follow-up continued for 12 months postintervention. Outcome measures
included glycated haemoglobin A1c (HbA1c) and psychological scores. RESULTS: The
HbA1c levels were available in 33 patients in each group for analysis. Between
group difference of the overall changes in HbA1c across the study period was
statically significant (P = .018). Geometric mean (range) HbA1c in the NDC group
deteriorated from 68 (46-113) to 78 (48-128) mmol/mol (ie, 8.4 [6.4-12.5]% to 9.3
[6.5-13.9]%; P = .001), but was maintained in the CBT group from 72 (46-129) to
73 (51-128) mmol/mol (P = .51) (ie, 8.7 [6.4-14]% to 8.9 [6.8-13.9]%). More
patients who have undergone CBT showed an improved or maintained HbA1c levels at
24 months (62.5% vs 35.5%, P = .032). Patients offered CBT with depressive scores
in the lowest tertile (least depressive symptoms) showed improvement in HbA1c
over time from 70 (46-102) to 67 (57-87) mmol/mol (P = .041) (ie, 8.6 [6.4-11.5]%
to 8.3 [7.4-10.1]%), but not in the NDC group. The CBT showed borderline
improvements in Children's Health Locus of Control (internal) scores over time
compared with NDC (P = .05). The self-efficacy score showed significant
improvement in both CBT (P < .001) and NDC (P = .03) groups over time.
CONCLUSIONS: CBT demonstrated better maintenance of glycaemic control compared
with NDC.
PMID- 28419662
TI - Ewing sarcoma of the sternal manubrium: first report of a case in Australasia and
review of the literature.
PMID- 28419663
TI - Total thyroidectomy for pressure symptoms in patients with Hashimoto's
thyroiditis.
AB - BACKGROUND: Hashimoto's thyroiditis (HT) is rarely on its own the indication for
thyroidectomy. However, surgery in patients with HT will be undertaken when there
is malignancy and may be required for pressure symptoms. Therefore, this study
aimed to investigate the indications for surgery in HT patients. METHODS: The
Monash University Endocrine Surgery Database was analysed from 1994 to 2013 for
patients with HT. Patients with HT were compared to a similar group of patients
with no HT on histopathology. Patient demographics, indication for surgery,
histopathology, gland weight and complications were analysed. RESULTS: A total of
2346 patients underwent total thyroidectomy during the study period. The median
age was 55 years. Eleven percent of patients had HT on final pathology
(259/2346). HT patients reported more pressure symptoms, 25.5% compared to those
with other pathology, 18.9% (P = 0.01). Patients with pressure symptoms had
heavier glands, 113 g compared to 85 g in those with other indications for
surgery (P = 0.048). Within the HT cohort, the median gland weight was 66 g
compared to 93 g in those without HT (P < 0.01). On multivariate analysis,
pressure symptoms as an indication for surgery was associated with HT (P < 0.01),
but age, gender and gland weight were not associated. In patients operated for
pressure with HT as the only pathology, 90% had relief of pressure symptoms.
CONCLUSION: Patients with HT were more likely to have pressure symptoms as an
indication for surgery independent of gland weights.
PMID- 28419664
TI - Effects of risk factors on periodontal disease defined by calibrated community
periodontal index and loss of attachment scores.
AB - OBJECTIVES: We evaluated whether and how the effects of risk factors on
periodontal disease (PD) were modified by measurement errors using community
periodontal index (CPI) and loss attachment (LA) in the community-based survey.
METHODS: A pilot validation study was performed to estimate the rates of false
negative and false positive for both CPI and LA in 31 subjects from different
regions using measurements from 12 well-trained dentists and a senior
periodontist as a gold standard. Afterward, a Taiwanese nationwide survey was
conducted by enrolling 3,860 participants to estimate the effect of each risk
factor on PD calibrated with both sensitivity and specificity of two indices.
RESULTS: The values obtained for the sensitivity to false-positive ratio for CPI
ranged widely from 1.12 to 7.71, indicating regional variation in both errors.
The calibrated adjusted odds ratio for smoking vs non-smoking was higher than the
uncalibrated odds ratio for PD defined by CPI (2.75 (2.01, 3.77) vs 2.02 (1.63,
2.52)) and LA (3.85 (2.44, 6.13) vs 1.93 (1.47, 2.54)) scores. Similar
underestimation was noted for other risk factors. CONCLUSION: The effects of risk
factors on PD measured using CPI and LA in a large population-based survey were
underestimated without correcting for measurement errors.
PMID- 28419666
TI - Microbial ecology of mountain glacier ecosystems: biodiversity, ecological
connections and implications of a warming climate.
AB - Glacier ecosystems are teeming with life on, beneath, and to a lesser degree,
within their icy masses. This conclusion largely stems from polar research, with
less attention paid to mountain glaciers that overlap environmentally and
ecologically with their polar counterparts in some ways, but diverge in others.
One difference lies in the susceptibility of mountain glaciers to the near-term
threat of climate change, as they tend to be much smaller in both area and
volume. Moreover, mountain glaciers are typically steeper, more dependent upon
basal sliding for movement, and experience higher seasonal precipitation. Here,
we provide a modern synthesis of the microbial ecology of mountain glacier
ecosystems, and particularly those at low- to mid-latitudes. We focus on five
ecological zones: the supraglacial surface, englacial interior, subglacial
bedrock-ice interface, proglacial streams and glacier forefields. For each, we
discuss the role of microbiota in biogeochemical cycling and outline ecological
and hydrological connections among zones, underscoring the interconnected nature
of these ecosystems. Collectively, we highlight the need to: better document the
biodiversity and functional roles of mountain glacier microbiota; describe the
ecological implications of rapid glacial retreat under climate change and resolve
the relative contributions of ecological zones to broader ecosystem function.
PMID- 28419665
TI - Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in
mice and antibody production after oral vaccination.
AB - The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases
(e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140
million people have chronic HCV infections and about 500 000 die yearly from HCV
related liver pathologies. To date, there is no licensed vaccine available to
prevent HCV infection and production of a HCV vaccine remains a major challenge.
Here, we report the successful production of the HCV E1E2 heterodimer, an
important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using
Agrobacterium-mediated transient expression technology. The wild-type dimer
(E1E2) and a variant without an N-glycosylation site in the E2 polypeptide
(E1E2?N6) were expressed, and appropriate N-glycosylation pattern and
functionality of the E1E2 dimers were demonstrated. The humoral immune response
induced by the HCV proteins was investigated in mice following oral
administration of lettuce antigens with or without previous intramuscular prime
with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding
only resulted in development of weak serum levels of anti-HCV IgM for both
antigens; however, the E1E2?N6 proteins produced higher amounts of secretory IgA,
suggesting improved immunogenic properties of the N-glycosylation mutant. The
mice group receiving the intramuscular injection followed by two oral boosts with
the lettuce E1E2 dimer developed a systemic but also a mucosal immune response,
as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In
summary, our study demonstrates the feasibility of producing complex viral
antigens in lettuce, using plant transient expression technology, with great
potential for future low-cost oral vaccine development.
PMID- 28419667
TI - Simple risk score for prediction of haemorrhagic complications after a
percutaneous renal biopsy.
AB - AIM: To derive a simple risk score to predict the individual risk of major
complications for patients undergoing a percutaneous renal biopsy procedure of
native kidneys. METHODS: The risk score was derived from a cohort of 1205 adult
patients subjected to percutaneous renal biopsy and assigned to training and
validation datasets. Factors associated with major complications were derived
from univariate analysis and then modelled by stepwise multivariate logistic
regression. Based on the odds ratio, independent predictors were assigned a
weighted integer. The risk score is calculated from the sum of the integers.
RESULTS: The overall incidence of major complications was 3.2%. Independent
factors associated with MC were lower pre-biopsy haemoglobin, lower platelets,
higher blood urea nitrogen, documented chronic kidney disease features in pre
biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A
score for pre-biopsy evaluation included the first four predictors and stratified
patients in three categories with increasing risk at higher scores (low-risk
0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good
discriminative power (AUC = 0.872). The addition of post-biopsy US findings
increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score
was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk
2.7%, high-risk 16.9%). CONCLUSION: The risk of major complications after a
percutaneous renal biopsy can be assessed by a simple risk score calculated from
readily available information.
PMID- 28419668
TI - Prevalence and associated variables of post-dialysis fatigue: Results of a
prospective multicentre study.
AB - AIM: The study aims to determine prevalence and severity of PDF and to define its
associated variables. METHODS: In five haemodialysis units of northern-centre
Italy, patients were regarded to suffer from PDF if they spontaneously offered
this complaint when asked the open-ended question: Do you feel better or worse
after dialysis? If worse, please specify in which way. A complaint of fatigue
would be probed further with questions directed at its duration, frequency and
intensity, allowing creation of a fatigue index of severity (one third of the sum
of these three parameters, each rated from 1 to 5). Patients were stratified into
three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3)
score > 3. RESULTS: We studied 271 patients: 164 had PDF and 107 did not. PDF
patients had significantly longer time of recovery after dialysis (TIRD). TIRD
was significantly associated with PDF duration, intensity, and frequency.
Patients with PDF were older and had a lower ADL score. At multivariate analysis,
PDF was significantly associated with TIRD. In a multivariate model that did not
include TIRD, PDF was independently associated with age and ADL. Sixty patients
had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and
dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the
ultrafiltration rate was lower. At multivariate analysis, PDF severity was
independently associated with TIRD. In the model without TIRD, PDF severity was
associated with ADL only. CONCLUSION: Post-dialysis fatigue is frequent and
associated with age and ADL. Dialytic variables seem unrelated to PDF.
PMID- 28419671
TI - Oral injuries in children presenting to a Japanese pediatric emergency room.
AB - BACKGROUND: Oral injuries are common among children, but studies on oral injury
according to the presence of foreign objects in the mouth are limited. The aim of
this study was to compare injury patterns and their effects in children
presenting to a Japanese pediatric emergency room (ER) with and without foreign
objects in the mouth. METHODS: Children who were brought to the ER at Tokyo
Metropolitan Children's Medical Center with oral injuries between 1 January 2011
and 31 December 2012, were included. Information regarding mechanism of injury,
object related to injury, required procedure, and disposition (i.e. placement
after ER evaluation: hospitalization or discharge) was collected. Injured
subjects with and without foreign objects in the mouth were compared. RESULTS:
Three hundred and nineteen subjects were included in analysis. Median age was 26
months. Labial mucosa, tongue, buccal mucosa, and teeth were major locations of
injury. Tumble (i.e. fall from standing) was the leading mechanism of injury
(50%). Seventy-one subjects (22%) were holding foreign objects in the mouth when
injury occurred. A toothbrush was the most common object (31%). Subjects with
foreign objects in the mouth were more likely to injure the posterior parts of
the mouth, and to require imaging (P = 0.04) and hospital admission (P < 0.001).
This was also the case for children with injury due to tumble. CONCLUSIONS:
Tumble (i.e. fall from standing) was the most common mechanism of injury.
Furthermore, requirement for medical resources increased if children had foreign
objects in their mouth. Preventive measures should focus on educating parents
about the dangers associated with children moving around while holding objects in
the mouth.
PMID- 28419670
TI - Sodium-glucose co-transporter (SGLT)2 and SGLT1 renal expression in patients with
type 2 diabetes.
AB - AIM: To quantify the expression of sodium-glucose co-transporter (SGLT)2 and
SGLT1, their cognate basolateral transporters, GLUT2 and GLUT1, and the
transcriptional regulator of SGLTs in renal tissue obtained from people with T2DM
and a group of well-matched people without diabetes. METHODS: We measured SGLT2
and SGLT1 expression in unaffected renal tissue from 19 people with T2DM and 20
people without diabetes, matched for age and estimated glomerular filtration rate
(controls), undergoing unilateral nephrectomy. Expression of SGLT2 and SGLT1, as
well as that of GLUT2 and GLUT1, was quantified using real-time and digital PCR;
an affinity-purified antibody against human SGLT2 was used to localize SGLT2 by
immunohistochemistry. RESULTS: SGLT2 expression was higher in control than T2DM
tissue (median [interquartile range] target/beta-actin 1.62 [2.02] vs 0.67
[0.61]; P < .0001), and SGLT1 trended in the same direction (0.98 [1.19] vs 0.44
[0.48]; P = .08). Immunohistochemistry clearly localized SGLT2 to the tubular
brush-border membranes, and was semi-quantitatively stronger in control than T2DM
tissue (5.0 [1.0] vs 4.0 [1.0] score units; P = .043). GLUT2 (control vs T2DM:
1.00 [0.69] vs 0.49 [0.36]) and GLUT1 expression (control vs T2DM: 0.86 [0.73] vs
0.35 [0.30]; P = .0007 for both) were closely correlated with those of the
respective SGLT partner. Hypoxia-inducible factor 1alpha, more abundant in
control than T2DM tissue, might be a transcription factor involved in the
modulation of SGLT2 expression. CONCLUSIONS: In whole renal tissue, expressions
of SGLT2/GLUT2 and SGLT1/GLUT1 are coupled and slightly lower in typical people
with T2DM as compared with well-matched people without diabetes.
PMID- 28419672
TI - Laparoscopic ventral mesh rectopexy - a video vignette.
PMID- 28419673
TI - Total mesorectal excision with Denonvilliers' fascia in anterior rectal tumours
using taTME technique - a video vignette.
PMID- 28419674
TI - Prognostic risk factors of first recurrence in patients with primary stages I-II
cutaneous malignant melanoma - from the population-based Swedish melanoma
register.
AB - BACKGROUND: Prognostic factors in patients with localized primary cutaneous
malignant melanoma (CMM) are well described. However, prognostic factors for
recurrence are less documented. OBJECTIVES: The aim of this study was to identify
prognostic risk factors for first recurrence in patients with localized stages I
II CMM using population-based data. METHODS: This study included 1437 CMM
patients registered in one region of Sweden during 1999-2012 follow-up through 31
December 2012. To identify first recurrence of CMM disease, data from a care data
warehouse, the pathology and radiology department registries were used. Patients
were also followed through a census register and the national Cause of Death
Register. RESULTS: The 5- and 10-year recurrence-free survival (RFS) were 85.7%
and 81.2%, respectively. The most common site of first recurrence was regional
lymph node metastasis closely followed by distant metastasis. After adjusting for
all prognostic factors, women had 50% lower risk of recurrence than men (HR =
0.5, 95% CI 0.4-0.7) and patients >=70 had higher risk compared to patients 55-69
years (HR = 1.7, 95% CI 1.2-2.5). Other significant prognostic factors for risk
of recurrence were tumour thickness, presence of ulceration, Clark's level of
invasion and histogenetic type. CONCLUSION: Tumour thickness was found to be the
predominant risk factor for recurrence. The prognostic factors for recurrence
coincided with prognostic factors for CMM death. The most common site of first
recurrence in stages I-II CMM is regional lymph node (42.8%) closely followed by
distant metastases (37.6%), a fact which has to be taken into consideration when
choosing follow-up strategies.
PMID- 28419675
TI - Melanin for space travel radioprotection.
PMID- 28419676
TI - Efficacy of dacarbazine as a rescue agent for histiocytic sarcoma in dogs.
AB - BACKGROUND: Canine histiocytic sarcoma (HS) is an aggressive neoplasm that is
generally associated with a poor prognosis. CCNU is considered first-line medical
therapy, although the majority of dogs ultimately develop progressive disease.
The objective of this study was to evaluate the efficacy of dacarbazine as a
rescue agent for HS. MATERIALS AND METHODS: Medical records of dogs diagnosed
with HS that received at least one dose of dacarbazine were reviewed. Information
collected and analyzed included signalment, disease distribution, treatment
history, dacarbazine treatments (including dose, interval and total number of
cycles), adverse events, and response to treatment. RESULTS: Seventeen dogs were
included, all of which had disseminated or metastatic disease and had received
prior treatment with CCNU. Three dogs achieved partial remission for an overall
response rate of 17.6%. The overall median event-free survival (EFS) was 21 days.
For dogs that experienced an objective response, the EFS was 70 days. Toxicity
secondary to dacarbazine was generally mild and self-limiting. CONCLUSION: In the
setting of advanced disease, dacarbazine appears to have modest activity against
HS and warrants further investigation.
PMID- 28419677
TI - Transanal minimally invasive surgery for excision of rectal carcinoid - a video
vignette.
PMID- 28419678
TI - Secondary compounds from exotic tree plantations change female mating preferences
in the palmate newt (Lissotriton helveticus).
AB - Selection can favour phenotypic plasticity in mate choice in response to
environmental factors that alter the costs and benefits of being choosy, or of
choosing specific mates. Human-induced environmental change could alter sexual
selection by affecting the costs of mate choice, or by impairing the ability of
individuals to identify preferred mates. For example, variation in mate choice
could be driven by environmentally induced differences in body condition (e.g.
health) that change the cost of choosiness, or by environmental effects on the
ability to detect or discriminate sexual signals. We teased apart these
possibilities experimentally, by comparing female mate choice in the palmate newt
Lissotriton helveticus between environments that mimic water from either native
oak forests or exotic eucalypt plantations. In laboratory two-choice mate trials
in clean water, females with prolonged exposure (21 days) to waterborne chemicals
leached from eucalypt leaves did not preferentially associate with the male with
a stronger immune response, but females exposed to water with chemicals from oak
leaves did. In contrast, female choice was unaffected by the immediate presence
or absence of eucalypt leachates during mate choice (using only females
previously held in oak-treated water). The habitat-related change in female
choice we observed is likely to be driven by effects of eucalypt leachates on
female physiology, rather than immediate inhibition of pheromone transmission or
blocking of pheromone reception.
PMID- 28419679
TI - Assessing the survival impact of perioperative opioid consumption in children and
adolescents undergoing cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy.
AB - BACKGROUND: Several studies in adult patients have suggested an unfavorable
association between opioid consumption and cancer progression. AIMS: This study
investigated the impact of opioid consumption on the survival of children and
adolescents undergoing cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy. METHODS: A retrospective study of patients <19 years who had
undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
was performed. Univariate and multivariate Cox proportional hazard analyses were
used to identify factors associated with recurrence-free survival and overall
survival. RESULTS: Seventy-five patients were identified. Median age was 11.6
years (range, 1.8-18.9), and 43% was female. Median perioperative opioid
consumption was 18.9 morphine dose equivalents per kilogram (range, 0.6-339.6).
There was no statistically significant association between opioid consumption and
recurrence-free survival [hazard ratio, 1.00; 95% confidence interval, (0.99
1.02), P = 0.55] or overall survival [hazard ratio 1.01; 95% confidence interval
(0.99-1.03), P = 0.22]. Independent prognostic factors associated with poor
survival included incomplete cytoreduction and extra-abdominal disease.
CONCLUSION: In this retrospective study of children and adolescents who had
undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy,
there was no statistically significant association between opioid consumption and
recurrence-free survival or overall survival.
PMID- 28419680
TI - BOLD neurovascular coupling does not change significantly with normal aging.
AB - Studies of cognitive function that compare the blood oxygenation level dependent
(BOLD) signal across age groups often require the assumption that neurovascular
coupling does not change with age. Tests of this assumption have produced mixed
results regarding the strength of the coupling and its relative time course.
Using deconvolution, we found that age does not have a significant effect on the
time course of the hemodynamic impulse response function or on the slope of the
BOLD versus stimulus duration relationship. These results suggest that in
cognitive studies of healthy aging, group differences in BOLD activation are
likely due to age-related changes in cognitive-neural interactions and
information processing rather than to impairments in neurovascular coupling. Hum
Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419681
TI - Oral mycobiome in community-dwelling elderly and its relation to oral and general
health conditions.
AB - OBJECTIVE: Oral fungal infection is generally associated with dysbiosis related
to antibiotic use, immunodeficiency, or frailty. However, fungal colonization in
a typical population without apparent symptoms and its associated conditions are
poorly understood. In this study, oral fungal colonization in community-dwelling
and independently living elderly populations was evaluated and factors affecting
fungal colonization were analyzed. SUBJECTS AND METHODS: The subjects (410; 181
males and 229 females) were 75-99 years of age; those under prior antibiotic use
were excluded. Fungal populations in the saliva were evaluated by PCR-based
molecular techniques. Body mass index (BMI), smoking habits, and oral health
conditions were examined. RESULTS: Salivary fungal amounts exceeded 104 CFU/ml
in 63 (15.4%) of 410 subjects. Candida albicans was most frequently detected
(98.4%), followed by Candida glabrata (54.0%), and Candida dubliniensis (38.1%)
in those subjects with fungi at 104 CFU/ml or over. Fungi at 104 CFU/ml or over
in the presence of C. glabrata or C. dubliniensis was significantly associated
with low BMI. CONCLUSIONS: Candida albicans, C. glabrata, and C. dubliniensis
dominated the oral mycobiome in Japanese community-dwelling elderly. Lower BMI
might signify compromised health status and thus could result in susceptibility
to specific candidiasis by C. glabrata and C. dubliniensis.
PMID- 28419682
TI - Game theoretical mapping of causal interactions underlying visuo-spatial
attention in the human brain based on stroke lesions.
AB - Anatomical studies conducted in neurological conditions have developed our
understanding of the causal relationships between brain lesions and their
clinical consequences. The analysis of lesion patterns extended across brain
networks has been particularly useful in offering new insights on brain-behavior
relationships. Here we applied multiperturbation Shapley value Analysis (MSA), a
multivariate method based on coalitional game theory inferring causal regional
contributions to specific behavioral outcomes from the characteristic functional
deficits after stroke lesions. We established the causal patterns of
contributions and interactions of nodes of the attentional orienting network on
the basis of lesion and behavioral data from 25 right hemisphere stroke patients
tested in visuo-spatial attention tasks. We calculated the percentage of damaged
voxels for five right hemisphere cortical regions contributing to attentional
orienting, involving seven specific Brodmann Areas (BA): Frontal Eye Fields, (FEF
BA6), Intraparietal Sulcus (IPS-BA7), Inferior Frontal Gyrus (IFG-BA44/BA45),
Temporo-Parietal Junction (TPJ-BA39/BA40), and Inferior Occipital Gyrus (IOG
BA19). We computed the MSA contributions of these seven BAs to three behavioral
clinical tests (line bisection, bells cancellation, and letter cancelation). Our
analyses indicated IPS as the main contributor to the attentional orienting and
also revealed synergistic influences among IPS, TPJ, and IOG (for bells
cancellation and line bisection) and between TPJ and IFG (for bells and letter
cancellation tasks). The findings demonstrate the ability of the MSA approach to
infer plausible causal contributions of relevant right hemisphere sites in
poststroke visuo-spatial attention and awareness disorders. Hum Brain Mapp, 2017.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28419684
TI - Should organs from hepatitis C virus-infected donors be used for transplantation
in the era of DAAs?
PMID- 28419685
TI - Scaffolds for epithelial tissue engineering customized in elastomeric molds.
AB - Restoration of soft tissue defects remains a challenge for surgical
reconstruction. In this study, we introduce a new approach to fabricate poly(d,l
lactic acid) (PDLLA) scaffolds with anatomical shapes customized to regenerate
three-dimensional soft tissue defects. Highly concentrated polymer/salt mixtures
were molded in flexible polyether molds. Microcomputed tomography showed that
with this approach it was possible to produce scaffolds with clinically
acceptable volume ratio maintenance (>90%). Moreover, this technique allowed us
to customize the average pore size and pore interconnectivity of the scaffolds by
using variations of salt particle size. In addition, this study demonstrated that
with the increasing porosity and/or the decreasing of the average pore size of
the PDLLA scaffolds, their mechanical properties decrease and they degrade more
slowly. Cell culture results showed that PDLLA scaffolds with an average pore
size of 100 um enhance the viability and proliferation rates of human gingival
epithelial cells up to 21 days. The simple method proposed in this article can be
extended to fabricate porous scaffolds with customizable anatomical shapes and
optimal pore structure for epithelial tissue engineering. (c) 2017 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 880-890, 2018.
PMID- 28419683
TI - Geographical differences in survival of dogs with non-Hodgkin lymphoma treated
with a CHOP based chemotherapy protocol.
AB - BACKGROUND: In humans geographical differences in the incidence and presentation
of various cancers have been reported. However, much of this information has not
been collected in veterinary oncology. AIM: The purpose of this study was to
determine if a geographic difference in progression free survival exists for dogs
with lymphoma treated within the US. MATERIALS AND METHODS: Medical records of
775 cases of canine lymphoma from 3 US regions (west, south and north), treated
with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from
referral institutions and were required to have received at least one doxorubicin
treatment and have follow up information regarding time to progression. RESULTS:
Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001),
immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were
seen between regions. Upon univariate analysis, progression free survival (PFS)
differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and
immunophenotype (p = 0.001). A multivariable Cox regression model showed that
dogs in the western region had a significantly shorter PFS when compared to the
south and east. CONCLUSION: PFS was significantly affected by stage, sub-stage
and phenotype.
PMID- 28419686
TI - Gastrointestinal mucormycosis in an immunocompromised host.
PMID- 28419687
TI - Skeletal muscle analyses: agreement between non-contrast and contrast CT scan
measurements of skeletal muscle area and mean muscle attenuation.
AB - Low skeletal muscle area (SMA) and muscle radiation attenuation (MRA) have been
associated with poor prognosis in various patient populations. Both non-contrast
and contrast CT scans are used to determine SMA and MRA. The effect of the use of
a contrast agent on SMA and MRA is unknown. Therefore, we investigated agreement
between these two scan options. SMA and MRA of 41 healthy individuals were
analysed on a paired non-contrast and contrast single CT scan, and agreement
between paired scan results was assessed with use of Bland-Altman plots,
intraclass correlation coefficients (ICCs), standard error of measurements (SEM)
and smallest detectable differences at a 95% confidence level (SDD95 ). Analyses
were stratified by tube voltage. Difference in SMA between non-contrast and
contrast scans made with a different tube voltage was 7.0 +/- 7.5 cm2 ; for scans
made with the same tube voltage this was 2.3 +/- 1.7 cm2 . Agreement was
excellent for both methods: ICC: 0.952, SEM: 7.2 cm2 , SDD95 : 19.9 cm2 and ICC:
0.997, SEM: 2.0 cm2 , SDD95 : 5.6 cm2 , respectively. MRA of scans made with a
different tube voltage differed 1.3 +/- 11.3 HU, and agreement was poor (ICC:
0.207, SEM: 7.9 HU, SDD95 : 21.8 HU). For scans made with the same tube voltage
the difference was 6.7 +/- 3.2 HU, and agreement was good (ICC: 0.682, SEM: 5.3
HU, SDD95 : 14.6 HU). In conclusion, SMA and MRA can be slightly influenced by
the use of contrast agent. To minimise measurement error, image acquisition
parameters of the scans should be similar.
PMID- 28419688
TI - Combined laparoscopic-robotic approach in complex re-operative colorectal surgery
- a video vignette.
PMID- 28419689
TI - Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in
human FARS2.
AB - Mutations in the mitochondrial aminoacyl-tRNA synthetases (mtaaRSs) can cause
profound clinical presentations, and have manifested as diseases with very
selective tissue specificity. To date most of the mtaaRS mutations could be
phenotypically recognized, such that clinicians could identify the affected
mtaaRS from the symptoms alone. Among the recently reported pathogenic variants
are point mutations in FARS2 gene, encoding the human mitochondrial PheRS.
Patient symptoms range from spastic paraplegia to fatal infantile Alpers
encephalopathy. How clinical manifestations of these mutations relate to the
changes in three-dimensional structures and kinetic characteristics remains
unclear, although impaired aminoacylation has been proposed as possible etiology
of diseases. Here, we report four crystal structures of HsmtPheRS mutants, and
extensive MD simulations for wild-type and nine mutants to reveal the structural
changes on dynamic trajectories of HsmtPheRS. Using steady-state kinetic
measurements of phenylalanine activation and tRNAPhe aminoacylation, we gained
insight into the structural and kinetic effects of mitochondrial disease-related
mutations in FARS2 gene.
PMID- 28419691
TI - The low diverse gastric microbiome of the jellyfish Cotylorhiza tuberculata is
dominated by four novel taxa.
AB - Cotylorhiza tuberculata is an important scyphozoan jellyfish producing population
blooms in the Mediterranean probably due to pelagic ecosystem's decay. Its
gastric cavity can serve as a simple model of microbial-animal digestive
associations, yet poorly characterized. Using state-of-the-art metagenomic
population binning and catalyzed reporter deposition fluorescence in situ
hybridization (CARD-FISH), we show that only four novel clonal phylotypes were
consistently associated with multiple jellyfish adults. Two affiliated close to
Spiroplasma and Mycoplasma genera, one to chlamydial 'Candidatus Syngnamydia',
and one to bacteroidetal Tenacibaculum, and were at least one order of magnitude
more abundant than any other bacteria detected. Metabolic modelling predicted an
aerobic heterotrophic lifestyle for the chlamydia, which were found
intracellularly in Onychodromopsis-like ciliates. The Spiroplasma-like organism
was predicted to be an anaerobic fermenter associated to some jellyfish cells,
whereas the Tenacibaculum-like as free-living aerobic heterotroph, densely
colonizing the mesogleal axis inside the gastric filaments. The association
between the jellyfish and its reduced microbiome was close and temporally stable,
and possibly related to food digestion and protection from pathogens. Based on
the genomic and microscopic data, we propose three candidate taxa: 'Candidatus
Syngnamydia medusae', 'Candidatus Medusoplasma mediterranei' and 'Candidatus
Tenacibaculum medusae'.
PMID- 28419692
TI - Associating Liver Partition and Portal vein ligation for Staged hepatectomy after
pre-operative chemotherapy.
AB - BACKGROUND: Recently a procedure termed 'Associating Liver Partition and Portal
vein ligation for Staged hepatectomy' (ALPPS) was developed to increase the
resectability of marginally resectable or locally unresectable liver tumours.
This study focused on the application of ALPPS in patients with advanced
colorectal liver metastases (CRLM) and pre-operative chemotherapy, with the aim
to investigate whether the latter still allows for sufficient hypertrophy of the
future liver remnant (FLR) following the first step of ALPPS. METHODS:
Retrospective analysis was performed on six patients suffering from advanced
CRLM. Analyses comprised demographical and basic clinical data, the perioperative
courses as well as short- and long-term outcomes. RESULTS: All patients presented
with bilobular CRLM and pre-operative chemotherapy of at least 6 months. Extended
right hemihepatectomy was performed in all cases, four patients additionally
received atypical resections in segments II/III. Mean FLR prior to step 1 of
ALPPS was 397.9 cm3 (121-753 cm3 ), on average representing 20.9% of the total
liver volume (13.2-27.1%). A mean hypertrophy of the FLR of 67.9% (32.5-94.1%)
was achieved. Overall, severe morbidity (Dindo Clavien >3a) occurred in two
patients. Following completion of ALPPS, mean post-operative disease-free
survival was 5.7 months (2.6-8.9 months). CONCLUSION: Despite pre-operative
chemotherapy, ALPPS seems to result in adequate liver hypertrophy, preventing
post-operative small-for-size syndrome. However, there might be a high risk of
tumour recurrence in patients with an aggressive tumour biology.
PMID- 28419693
TI - Ag-loaded MgSrFe-layered double hydroxide/chitosan composite scaffold with
enhanced osteogenic and antibacterial property for bone engineering tissue.
AB - Bone tissue engineering scaffolds for the reconstruction of large bone defects
should simultaneously promote osteogenic differentiation and avoid postoperative
infection. Herein, we develop, for the first time, Ag-loaded MgSrFe-layered
double hydroxide/chitosan (Ag-MgSrFe/CS) composite scaffold. This scaffold
exhibits three-dimensional interconnected macroporous structure with a pore size
of 100-300 MUm. The layered double hydroxide nanoplates in the Ag-MgSrFe/CS show
lateral sizes of 200-400 nm and thicknesses of ~50 nm, and the Ag nanoparticles
with particle sizes of ~20 nm are uniformly dispersed on the scaffold surfaces.
Human bone marrow-derived mesenchymal stem cells (hBMSCs) present good adhesion,
spreading, and proliferation on the Ag-MgSrFe/CS composite scaffold, suggesting
that the Ag and Sr elements in the composite scaffold have no toxicity to hBMSCs.
When compared with MgFe/CS composite scaffold, the Ag-MgSrFe/CS composite
scaffold has better osteogenic property. The released Sr2+ ions from the
composite scaffold enhance the alkaline phosphatase activity of hBMSCs, promote
the extracellular matrix mineralization, and increase the expression levels of
osteogenic-related RUNX2 and BMP-2. Moreover, the Ag-MgSrFe/CS composite scaffold
possesses good antibacterial property because the Ag nanoparticles in the
composite scaffold effectively prevent biofilm formation against S. aureus.
Hence, the Ag-MgSrFe/CS composite scaffold with excellent osteoinductivity and
antibacterial property has a great potential for bone tissue engineering. (c)
2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 863
873, 2018.
PMID- 28419694
TI - Quantitative depth resolved microcirculation imaging with optical coherence
tomography angiography (Part IotaIota): Microvascular network imaging.
AB - In this work, we review the main phenomena that have been explored in OCT
angiography to image the vessels of the microcirculation within living tissues
with the emphasis on how the different processing algorithms were derived to
circumvent specific limitations. Parameters are then discussed that can
quantitatively describe the depth-resolved microvascular network for possible
clinic diagnosis applications. Finally,future directions in continuing OCT
development are discussed. This article is protected by copyright. All rights
reserved.
PMID- 28419695
TI - Flavivirus cross-reactivity, Guillain-Barre syndrome, and hematopoietic stem cell
transplant patient: A comment.
PMID- 28419696
TI - Risk Factors Associated with Pain on Chronic Intermittent Hemodialysis: A
Systematic Review.
AB - OBJECTIVES: The aim of the study was to define risk factors related to pain in
adult end-stage renal disease (ESRD) patients on chronic intermittent
hemodialysis (HD) by developing a systematic review of published data. METHODS:
The search was conducted from MEDLINE, Scopus, PsycINFO, and the Cumulative Index
to Nursing and Allied Health Literature (CINAHL). Manuscripts in all languages
were considered. Two authors performed each step independently, and all
disagreements were resolved after discussion with the third author. Quality of
studies was analyzed using the Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) checklist and Cochrane risk of bias tool.
RESULTS: A total of 67 studies with 7,818 participants were included (median
number of participants = 60). Most of the studies reported common factors such as
age, gender, body mass index, race/ethnicity, marital status, duration of HD
treatment since initiation of HD, different comorbidities, and biochemical
parameters. Other studies reported more specific factors such as type, regimen or
place of hemodialysis, type of dialyzer, dialysis phase, type of dialyzer
membrane, administration site, type of preparation, and dose of erythropoiesis
stimulating agent (ESA). The studies indicate that these factors may contribute
to increased pain in general and also promote development of different pain
modalities of various locations and causes in HD patients (eg, pain in general,
pain related to arteriovenous access, headache, musculoskeletal pain, ESA
application pain). DISCUSSION: Multiple factors for various types of pain in very
heterogeneous populations and heterogeneous settings were analyzed in the
literature. The results turned out to be inconsistent between the studies. Future
large-scale studies are required, taking into the account limitations of the
current evidence base.
PMID- 28419697
TI - Defensive High-Anxious Individuals Demonstrate Difference Responses to Pain
Management to Those with Lower Levels of Defensiveness and Anxiety.
AB - OBJECTIVES: Few studies have considered the effect of Weinberger et al.'s
personality types on the management of pain. The aims of this study were to (1)
identify whether the relationships between pain intensity, cognitive factors, and
disability at 3 and 6 months postbaseline differ as a result of personality type;
and (2) identify whether personality type affects the likelihood of achieving a
minimal clinically important change in pain intensity or disability at 3 and 6
months. METHOD: Patients completed a set of validated questionnaires assessing
personality type, cognitive factors, pain intensity, and disability at 3 and 6
months postbaseline. RESULTS: A greater proportion of defensive high-anxious
individuals reported improvement for both pain (3 months = 25%; 6 months = 38%)
and disability (3 months = 35%; 6 months = 50%) and showed stronger links between
improvements in pain and disability and baseline psychological factors than
nonextreme individuals. CONCLUSIONS: The high proportion of defensive high
anxious individuals highlights the need for psychologically based interventions
to be delivered earlier in the care process. Stratifying the population, based on
personality type, may allow for more targeted interventions, which could be more
cost effective and reduce the number of patients remaining in the care system.
PMID- 28419698
TI - Collagen barrier membranes do not adsorb hypoxia mimetic activity-Activity of
gingival fibroblasts cultured directly on collagen barrier membranes loaded with
hypoxia mimetic agents.
AB - Hypoxia-based strategies for applications in oral surgery and periodontology have
been proposed where collagen barrier membranes (CBM) are loaded with hypoxia
mimetic agents (HMA) to induce a pro-angiogenic response. While it was found that
CBM release HMA, it remained unclear if CBM adsorb HMA activity. Here we
evaluated the response of oral cells cultured on CBM, supplemented with the HMA
dimethyloxalylglycine (DMOG), desferrioxamine (DFO), and l-mimosine (l-MIM).
Gingival fibroblasts (GF) were cultured on unwashed CBM as well as on CBM that
had been washed with serum-free medium for 48 hours. The pro-angiogenic response
was measured based on vascular endothelial growth factor (VEGF) production.
Viability and proliferation were assessed based on MTT and BrdU assays. We found
that GF seeded onto CBM loaded with DFO and l-MIM, but not DMOG, showed an
increase in VEGF to 6.1-fold and 7.7-fold compared to unloaded CBM, respectively.
Cells remained vital, but a trend for decreased proliferation was observed on
DMOG and DFO-loaded CBM which did not reach the level of significance. Evaluation
of washed CBM revealed no difference between the unloaded CBM and CBM
supplemented with DMOG, DFO, or l-MIM. In conclusion, our results suggest that
CBM do not adsorb hypoxia mimetic activity but release HMA within the first
hours. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
106B: 874-879, 2018.
PMID- 28419699
TI - Cystic mesenteric lymphangioma: a case report.
PMID- 28419700
TI - Pregnancy Ambivalence and Long-Acting Reversible Contraceptive (LARC) Use Among
Young Adult Women: A Qualitative Study.
AB - CONTEXT: Many young adults are unclear about how much they want to have, or
prevent having, a baby. However, pregnancy ambivalence is an underexamined factor
in the uptake of long-acting reversible contraceptive (LARC) methods-IUDs and
implants-the most effective methods available. METHODS: In 2014, investigators
conducted six focus groups and 12 interviews with 50 women aged 18-29 in Dane
County, Wisconsin; participants were either university students or community
residents receiving public assistance. A modified grounded theory approach was
used to analyze the data. RESULTS: Four themes emerged. First, participants
described a pregnancy desire spectrum: Those strongly motivated to avoid
pregnancy were most receptive to LARC methods, while those with less clear or
mixed desires worried that these methods would prevent "accidental" pregnancies
that might not be unwelcome. Second, women within a few years of wanting children
perceived LARC methods as too "permanent," despite awareness of their
reversibility. Third, age and life stage were important factors: Younger women
and those attending school or beginning careers were more likely than others to
consider these methods because they had clearer motivations to avoid pregnancy.
Finally, relationship stage influenced receptiveness to LARC methods: Women in
newer relationships were more receptive than were those in longer term
relationships who imagined having a baby with their partner someday. CONCLUSION:
Effectiveness is not the only factor in women's selection and use of
contraceptive methods. Individual preferences will lead some women to choose non
LARC methods even when fully informed of their options.
PMID- 28419701
TI - OMIP-038: Innate immune assessment with a 14 color flow cytometry panel.
PMID- 28419702
TI - Evaluation of the truebeam machine performance check (MPC): mechanical and
collimation checks.
AB - Machine performance check (MPC) is an automated and integrated image-based tool
for verification of beam and geometric performance of the TrueBeam linac. The
aims of the study were to evaluate the performance of the MPC geometric tests
relevant to beam collimation (MLC and jaws) and mechanical systems (gantry and
collimator). Evaluation was performed by comparing MPC to QA tests performed
routinely in the department over a 4-month period. The MPC MLC tests were
compared to an in-house analysis of the Picket Fence test. The jaw positions were
compared against an in-house EPID-based method, against the traditional light
field and graph paper technique and against the Daily QA3 device. The MPC
collimator and gantry were compared against spirit level and the collimator
further compared to Picket Fence analysis. In all cases, the results from the
routine QA procedure were presented in a form directly comparable to MPC to allow
a like-to-like comparison. The sensitivity of MPC was also tested by deliberately
miscalibrating the appropriate linac parameter. The MPC MLC was found to agree
with Picket Fence to within 0.3 mm and the MPC jaw check agreed with in-house
EPID measurements within 0.2 mm. All MPC parameters were found to be accurately
sensitive to deliberately introduced calibration errors. For the tests evaluated,
MPC appears to be suitable as a daily QA check device.
PMID- 28419703
TI - Exercise capacity following pediatric heart transplantation: A systematic review.
AB - Pediatric HTs account for 13% of all HTs with >60% of recipients surviving at
least 10 years post-HT. The purpose of this systematic review is to synthesize
the literature on exercise capacity of pediatric HT recipients to improve
understanding of the mechanisms that may explain the decreased exercise capacity.
Six databases were searched for studies that compared the exercise capacity of HT
recipients <=21 years old with a control group or normative data. Sixteen studies
were included. Pediatric HT recipients, as compared to controls or normative
data, exhibit significantly higher resting HR, and at peak exercise exhibit
significantly decreased HR, VO2 , power, work, minute ventilation, and exercise
duration. Peak VO2 appears to improve within the first 2.5 years post-HT; peak
work remains constant; and there is inconclusive evidence that peak HR, HR
recovery, and HR reserve improve with time since HT. These results are discussed
in the context of the mechanisms that may explain the impaired exercise capacity
of pediatric HT recipients, including chronotropic incompetence, graft
dysfunction, side effects of immunosuppression therapy, and deconditioning. In
addition, the limited literature on rehabilitation after pediatric HT is
summarized.
PMID- 28419704
TI - Robustness of a model microbial community emerges from population structure among
single cells of a clonal population.
AB - Microbial populations can withstand, overcome and persist in the face of
environmental fluctuation. Previously, we demonstrated how conditional gene
regulation in a fluctuating environment drives dilution of condition-specific
transcripts, causing a population of Desulfovibrio vulgaris Hildenborough (DvH)
to collapse after repeatedly transitioning from sulfate respiration to syntrophic
conditions with the methanogen Methanococcus maripaludis. Failure of the DvH to
successfully transition contributed to the collapse of this model community. We
investigated the mechanistic basis for loss of robustness by examining whether
conditional gene regulation altered heterogeneity in gene expression across
individual DvH cells. We discovered that robustness of a microbial population
across environmental transitions was attributable to the retention of cells in
two states that exhibited different condition-specific gene expression patterns.
In our experiments, a population with disrupted conditional regulation
successfully alternated between cell states. Meanwhile, a population with intact
conditional regulation successfully switched between cell states initially, but
collapsed after repeated transitions, possibly due to the high energy
requirements of regulation. These results demonstrate that the survival of this
entire model microbial community is dependent on the regulatory system's
influence on the distribution of distinct cell states among individual cells
within a clonal population.
PMID- 28419705
TI - Intravoxel incoherent motion MRI for the differentiation of benign, intermediate,
and malignant solid soft-tissue tumors.
AB - PURPOSE: To determine the diagnostic potential of apparent diffusion coefficient
(ADC) and intravoxel incoherent motion (IVIM)-derived parameters for the
differentiation of benign, intermediate, and malignant solid soft-tissue tumors.
MATERIALS AND METHODS: The Institutional Review Board approved this prospective
study, and informed consent was obtained. IVIM imaging was performed in 64
patients including 44 benign, 6 intermediate, and 14 malignant solid soft-tissue
tumors at 1.5T. The IVIM parameters of the soft-tissue tumors were assessed using
the Kruskal-Wallis test. The diagnostic performance of the parameters was
evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The
ADC and true diffusion coefficient (D) values of malignancies (1.28 +/- 0.31,
1.06 +/- 0.23 [*10-3 mm2 /sec]) were significantly lower than those of
intermediate (1.49 +/- 0.54, 1.30 +/- 0.50 [*10-3 mm2 /sec]), or benign soft
tissue tumors (1.62 +/- 0.37, 1.36 +/- 0.33 [*10-3 mm2 /sec]) (P = 0.007 and P =
0.009, respectively). In the differential diagnosis of malignancies from benign
tumors, ADC demonstrated the highest area under the curve (Az) value (Az =
0.793). The perfusion fraction (f) values of intermediate soft-tissue tumors
(8.41 +/- 2.73) were significantly different from those of benign and malignant
tumors (14.70 +/- 5.37 [P = 0.002]; 14.44 +/- 5.31 [P = 0.021]). f showed the
highest Az value in differentiating intermediate from benign, and malignant soft
tissue tumors (Az = 0.90, and Az = 0.833, respectively). The pseudodiffusion
coefficient (D*) values of malignant soft-tissue tumors (144.40 +/- 24.88 [*10-3
mm2 /sec]) were significantly higher than those of benign tumors (124.96 +/-
26.24 [*10-3 mm2 /sec]) (P = 0.019). CONCLUSION: IVIM imaging may be helpful for
differentiating benign, intermediate, and malignant solid soft-tissue tumors.
LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
2017;46:1611-1618.
PMID- 28419707
TI - Current Resources for Evidence-Based Practice, March/April 2017.
PMID- 28419708
TI - Willingness to Pay for a Maternity Waiting Home Stay in Zambia.
AB - INTRODUCTION: Complications of pregnancy and childbirth can pose serious risks to
the health of women, especially in resource-poor settings. Zambia has been
implementing a program to improve access to emergency obstetric and neonatal
care, including expansion of maternity waiting homes-residential facilities
located near a qualified medical facility where a pregnant woman can wait to give
birth. Yet it is unclear how much support communities and women would be willing
to provide to help fund the homes and increase sustainability. METHODS: We
conducted a mixed-methods study to estimate willingness to pay for maternity
waiting home services based on a survey of 167 women, men, and community elders.
We also collected qualitative data from 16 focus group discussions to help
interpret our findings in context. RESULTS: The maximum willingness to pay was
5.0 Zambian kwacha or $0.92 US dollars per night of stay. Focus group discussions
showed that willingness to pay is dependent on higher quality of services such as
food service and suggested that the pricing policy (by stay or by night) could
influence affordability and use. DISCUSSION: While Zambians seem to value and be
willing to contribute a modest amount for maternity waiting home services,
planners must still address potential barriers that may prevent women from
staying at the shelters. These include cash availability and affordability for
the poorest households.
PMID- 28419710
TI - Updates From the Literature, March/April 2017.
PMID- 28419709
TI - Job Satisfaction and Subjective Well-Being Among Midwives: Analysis of a
Multinational Cross-Sectional Survey.
AB - INTRODUCTION: There is a considerable amount of empirical evidence to indicate a
positive association between an employee's subjective well-being and workplace
performance and job satisfaction. Compared with nursing research, there is a
relative lack of consistent scientific evidence concerning midwives' subjective
well-being and its determinants related to domains of job satisfaction. The
purpose of the study was to examine the association between the domains of job
satisfaction and components of subjective well-being in hospital midwives.
METHODS: This cross-sectional descriptive study involved 1190 hospital midwives
from 7 countries. Job satisfaction was measured by the McCloskey/Mueller
Satisfaction Scale. Subjective well-being was conceptualized in the study by the
2 components (the affective and the cognitive component). The affective component
of subjective well-being (ie, emotional well-being) was assessed by the Positive
and the Negative Affect Scale. The cognitive component of subjective well-being
(ie, life satisfaction) was measured by the Personal Well-Being Index. Pearson
correlations and multiple regression analyses were used to determine associations
between variables. RESULTS: Findings from correlation and regression analyses
indicated an overall weak association between the domains of job satisfaction and
components of subjective well-being. Satisfaction with extrinsic rewards,
coworkers, and interaction opportunities accounted for only 13% of variance in
the cognitive component (life satisfaction). The affective component (emotional
well-being) was weakly associated with satisfaction with control and
responsibility. DISCUSSION: The low amount of variance suggests that neither
component of subjective well-being is influenced by the domains of job
satisfaction. Further studies should focus on identifying other predictors of
subjective well-being among midwives. A better understanding of how specific job
facets are related to the subjective well-being of midwives might assist
employers in the design of counseling and intervention programs for subjective
well-being of midwives in the workplace and workplace performance.
PMID- 28419711
TI - Writing for the Journal of Midwifery & Women's Health: Beyond Research.
PMID- 28419712
TI - Comparison of safety and efficacy of image-guided enema reduction techniques for
paediatric intussusception: A review of the literature.
AB - There is variable international practice regarding the technique used for image
guided enema reduction in paediatric intussusception. A recent meta-analysis
found pneumatic reduction to be more effective than hydrostatic techniques.
Clinical practice variation may impact on perforation rates, ionizing radiation
exposure and requirement for surgery. The aim of this study was to review the
literature regarding the efficacy and safety of fluoroscopically guided pneumatic
reduction (FGPR) compared to ultrasound (US) guided intussusception reduction
(USGIR) techniques for paediatric intussusception treatment. Articles were
identified by searching OVID Medline on 21/02/14 and by scanning retrieved
articles reference lists. The search was repeated on 30/09/15. Systematic reviews
(SR) were appraised with the PRISMA critical appraisal tool. Primary studies
underwent a separate critical appraisal process. Successful reductions and
perforations per attempt were calculated for each study. Pooled estimates of
proportions were calculated for each of these dichotomous outcomes. A SR and 42
primary studies were included in the review. No randomised control trial (RCT)
study was included. Non-randomised comparative studies and non-comparative
studies suggest that hydrostatic reduction under US control has a similar
efficacy and safety profile to pneumatic reduction under fluoroscopic control,
but USGIR data are dominated by a single large, non-comparative study performed
in China. US-guided intussusception reduction should be considered an alternative
to FGPR as it has similar efficacy and safety, and affords no ionised radiation
exposure. However, RCT data are required to inform practice.
PMID- 28419713
TI - NT-proBNP predicts mortality in adults with transposition of the great arteries
late after Mustard or Senning correction.
AB - OBJECTIVE: The patients after Mustard and Senning corrections of transposition of
the great arteries (TGA) are at an increased risk of unexpected death. The aim of
this study was to identify markers allowing risk stratification of patients after
atrial switch correction of TGA to provide them with optimum care. METHODS AND
RESULTS: In this study, 87 patients were retrospectively evaluated after atrial
switch correction of TGA followed-up between 2005 and 2015. The mortality during
the follow-up was 9% (8 cardiac deaths). Markers significantly predictive of
death using univariable Cox proportional hazard ratio survival analysis were: N
terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction and end
diastolic dimension of the systemic right ventricle, mitral E, e', and s'.
Surprisingly, the Doppler parameters of mitral valve in subpulmonary ventricle
were more important for prognosis than those of systemic tricuspid valve. In
multivariable analysis, the only independent predictors of mortality were NT
proBNP (P = .00048; AUC 0.97) and the velocity of early diastolic filling (mitral
E) in subpulmonary ventricle (P = .01815; AUC 0.81). According to Kaplan-Meier
survival analysis, patients with NT-proBNP > 1000 pg/ml are at high risk of
death. Patients with mitral E < 68 cm/s are also at an increased risk of death.
CONCLUSIONS: NT-proBNP is the most reliable prognostic mortality factor and
should be measured regularly in TGA patients after Mustard or Senning correction.
Diastolic filling velocity of the subpulmonary left ventricle (mitral E) may be
more important for prognosis than systolic function of the systemic right
ventricle.
PMID- 28419714
TI - Young people's beliefs about the risk of bowel cancer and its link with physical
activity.
AB - OBJECTIVES: The primary objective was to explore young people's risk appraisals
of bowel cancer, including whether they had a coherent understanding of the
protective effects of physical activity (PA). A secondary objective was to
examine whether the illness risk representations (IRRs) framework could be used
to understand beliefs underlying bowel cancer risk appraisals. DESIGN:
Qualitative. METHODS: Framework analysis of semi-structured interviews with 19
people aged 14-17 years. RESULTS: Participants judged their risk of getting bowel
cancer as low. This was based on a lack of family history of cancer and their
current lifestyle behaviours, which were viewed as having a protective effect, or
because they planned on making change to their lifestyle in the future when
disease risk became more relevant. Participants were not aware of, and struggled
to understand, the link between PA and bowel cancer. They also lacked knowledge
of the effects of, or treatments for, bowel cancer. Beliefs underlying judgements
about the risk of bowel cancer fitted the IRR framework reasonably well.
CONCLUSIONS: The present research suggests that interventions designed to
increase PA with a view to reducing the risk of bowel cancer should aim to make
the future risk of bowel cancer feel more tangible, help young people to
understand the full range of consequences, explain how and why preventative
behaviours such as PA are effective in reducing risk, and emphasize that the
typical late presentation of symptoms, and therefore investigation by health care
services, reduces treatability. Statement of contribution What is already known
on this subject? Physical activity (PA) performed throughout the lifespan can
have a protective effect on bowel cancer, but levels of PA are low among young
people. Changing beliefs about the risk of getting bowel cancer may be a useful
strategy in motivating PA. What does this study add? Increased understanding of
how young people think about bowel cancer and the relationship between PA and
cancer. Identification of strategies for increasing young adults' appraisals of
the likelihood and severity of bowel cancer. Evidence to support the validity of
illness risk representations framework.
PMID- 28419715
TI - A survey on faculty perspectives on the transition to a biochemistry course-based
undergraduate research experience laboratory.
AB - It will always remain a goal of an undergraduate biochemistry laboratory course
to engage students hands-on in a wide range of biochemistry laboratory
experiences. In 2006, our research group initiated a project for in silico
prediction of enzyme function based only on the 3D coordinates of the more than
3800 proteins "of unknown function" in the Protein Data Bank, many of which
resulted from the Protein Structure Initiative. Students have used the ProMOL
plugin to the PyMOL molecular graphics environment along with BLAST, Pfam, and
Dali to predict protein functions. As young scientists, these undergraduate
research students wanted to see if their predictions were correct and so they
developed an approach for in vitro testing of predicted enzyme function that
included literature exploration, selection of a suitable assay and the search for
commercially available substrates. Over the past two years, a team of faculty
members from seven different campuses (California Polytechnic San Luis Obispo,
Hope College, Oral Roberts University, Rochester Institute of Technology, St.
Mary's University, Ursinus College, and Purdue University) have transferred this
approach to the undergraduate biochemistry teaching laboratory as a Course-based
Undergraduate Research Experience. A series of ten course modules and eight
instructional videos have been created (www.promol.org/home/basil-modules-1) and
the group is now expanding these resources, creating assessments and evaluating
how this approach helps student to grow as scientists. The focus of this
manuscript will be the logistical implications of this transition on campuses
that have different cultures, expectations, schedules, and student populations.
(c) 2017 by The International Union of Biochemistry and Molecular Biology,
45(5):426-436, 2017.
PMID- 28419716
TI - Effect of dehydration and rehydration intervals on fracture resistance of
reattached tooth fragments using a multimode adhesive.
AB - BACKGROUND/AIMS: The tooth fragment bonding technique, frequently used to restore
traumatized teeth, may be affected by dehydration/rehydration periods. The aim of
this study was to evaluate the effects of different dry and wet storage intervals
on multimode adhesive bonding between reattached fragments and teeth. MATERIALS
AND METHODS: Eighty-four bovine incisors were fractured and randomized into
groups (n=12). After teeth fracturing, each specimen was assigned to one of the
following groups: G0: control group (sound tooth); GA1 and GA2: 1-h dehydration
and a 15-min or 24-hours rewetting period, respectively; GB1 and GB2: 24-hours
dehydration and a 15-minutes or 24-hours rewetting period, respectively; and GC:
1-hour (GC1) or 24-hours (GC2) dehydration period only. Tooth fragments were then
reattached using a multimode adhesive in a self-mode technique with a flowable
resin composite. The fracture resistance was evaluated in a universal testing
machine under a compressive load (1 mm/min-1 ). Data were submitted to two-way
analysis of variance and post hoc Tukey test (5%). RESULTS: No significant
interaction between dehydration and rehydration intervals was observed (P>.05).
Only the step of rehydration significantly affected the reattachment strength
when compared to the groups submitted only to dehydration, regardless of the
interval (15 minutes or 24 hours). CONCLUSION: Rehydrating a tooth fragment for
15 minutes before bonding with a multimode adhesive maintained sufficient
moisture to increase reattachment strength.
PMID- 28419717
TI - Ligand recognition properties of the vasopressin V2 receptor studied under QSAR
and molecular modeling strategies.
AB - The design of new drugs that target vasopressin 2 receptor (V2R) is of vital
importance to develop new therapeutic alternatives to treat diseases such as
heart failure, polycystic kidney disease. To get structural insights related to
V2R-ligand recognition, we have used a combined approach of docking, molecular
dynamics simulations (MD) and quantitative structure-activity relationship (QSAR)
to elucidate the detailed interaction of the V2R with 119 of its antagonists. The
three-dimensional model of V2R was built by threading methods refining its
structure through MD simulations upon which the 119 ligands were subjected to
docking studies. The theoretical results show that binding recognition of these
ligands on V2R is diverse, but the main pharmacophore (electronic and pi-pi
interactions) is maintained; thus, this information was validated under QSAR
results. QSAR studies were performed using MLR analysis followed by ANN analysis
to increase the model quality. The final equation was developed by choosing the
optimal combination of descriptors after removing the outliers. The applicability
domains of the constructed QSAR models were defined using the leverage and
standardization approaches. The results suggest that the proposed QSAR models can
reliably predict the reproductive toxicity potential of diverse chemicals, and
they can be useful tools for screening new chemicals for safety assessment.
PMID- 28419718
TI - Shifting microbial communities sustain multiyear iron reduction and
methanogenesis in ferruginous sediment incubations.
AB - Reactive Fe(III) minerals can influence methane (CH4 ) emissions by inhibiting
microbial methanogenesis or by stimulating anaerobic CH4 oxidation. The balance
between Fe(III) reduction, methanogenesis, and CH4 oxidation in ferruginous
Archean and Paleoproterozoic oceans would have controlled CH4 fluxes to the
atmosphere, thereby regulating the capacity for CH4 to warm the early Earth under
the Faint Young Sun. We studied CH4 and Fe cycling in anoxic incubations of
ferruginous sediment from the ancient ocean analogue Lake Matano, Indonesia, over
three successive transfers (500 days in total). Iron reduction, methanogenesis,
CH4 oxidation, and microbial taxonomy were monitored in treatments amended with
ferrihydrite or goethite. After three dilutions, Fe(III) reduction persisted only
in bottles with ferrihydrite. Enhanced CH4 production was observed in the
presence of goethite, highlighting the potential for reactive Fe(III) oxides to
inhibit methanogenesis. Supplementing the media with hydrogen, nickel and
selenium did not stimulate methanogenesis. There was limited evidence for Fe(III)
dependent CH4 oxidation, although some incubations displayed CH4 -stimulated
Fe(III) reduction. 16S rRNA profiles continuously changed over the course of
enrichment, with ultimate dominance of unclassified members of the order
Desulfuromonadales in all treatments. Microbial diversity decreased markedly over
the course of incubation, with subtle differences between ferrihydrite and
goethite amendments. These results suggest that Fe(III) oxide mineralogy and
availability of electron donors could have led to spatial separation of Fe(III)
reducing and methanogenic microbial communities in ferruginous marine sediments,
potentially explaining the persistence of CH4 as a greenhouse gas throughout the
first half of Earth history.
PMID- 28419719
TI - Spectroscopic evidences of toxic trans-crotonaldehyde trapped and transformed by
resveratrol to prevent the damage of mitochondrial DNA.
AB - The purpose of this study is to probe the spectroscopic evidences of toxic trans
crotonaldehyde (TCA) trapped and transformed by resveratrol (Res) to prevent the
damage of mitochondrial DNA. In aldehyde dehydrogenase (ALDH) at the different pH
or mitochondria, the spectroscopic characteristics of TCA trapped and transformed
by Res were observed by means of both UV-vis and Raman spectra. When Res
interacted with TCA, TCA peak at 316 nm immediately disappeared while Res main
peak at 305 nm and shoulder peak at 320 nm were dramatically changed, Raman peaks
of TCA at 1,688 cm-1 assigned to CH?O and 1,641 cm-1 affiliated to C?C were
strikingly shifted, Raman peaks of Res itself were significantly displaced or
disappeared, especially in mitochondria and ALDH at different pH. The active
groups of Res were the ?OH at C5 and C10 . The results of theoretical
calculations are in agreement on the whole with the experimental data. The Res
plays undoubtedly an important role via the structural change in TCA. The toxic
CH?O of TCA was effectively trapped and transformed by Res by means of itself ?OH
at C5 and C10 . The mitochondrial alkaline microenvironment and ALDH promoted the
elimination of toxic TCA. (c) 2017 IUBMB Life, 69(7):500-509, 2017.
PMID- 28419720
TI - Illusory hand ownership in a patient with personal neglect for the upper limb,
but no somatoparaphenia.
AB - The symptoms of patients with left personal neglect are characterized by
inattention towards contralesional (left) body parts while at the same time
explicitly ascertaining ownership for the neglected hemibody. It is currently
unknown if personal neglect is associated with more subtle or implicit
disturbances of own body perception and body ownership as measured with the
rubber hand illusion. In this study, we report data from a patient with a right
hemispheric lesion and personal neglect, without associated somatosensory
deficits. We administered to the patient (and to 12 age-matched controls) the
rubber hand illusion paradigm to the right and left hands, to elicit illusory
ownership for a fake hand, before and after recovery from personal neglect for
the left arm. In a first session, run when the patient showed personal neglect
affecting the left arm, he experienced a significantly enhanced subjective
illusion of embodiment for the left fake hand as compared to the right hand (as
assessed through a standard questionnaire). After recovery from personal neglect
for the left arm (second session), the results of the left and right rubber hand
illusion experiments were comparable, with no modulation of hand ownership. We
argue that personal neglect may consist not only in an inattentional disorder,
but also in a deficit of multisensory body representation characterized by a high
sensitivity to experimental manipulations of subjective aspects of body
ownership.
PMID- 28419721
TI - Classical image of the pulmonary artery aneurysm secondary to idiopathic
pulmonary hypertension.
PMID- 28419722
TI - Role of monocyte tissue factor on patients with non-small cell lung cancer.
AB - BACKGROUND: To examine the expression of D-dimer, fibrinogen (FIB), leukocyte, C
reactive protein (CRP) and tissue factor (TF) released from monocyte in non-small
cell lung cancer (NSCLC) patients with or without venous thromboembolism (VTE)
and analyse the correlation, to explore the possible mechanisms. METHODS: Seventy
two patients confirmed the diagnosis of lung cancer, among whom 10 with VTE were
enrolled into the study from November 2012 to January 2014 in the First
Affiliated Hospital of Fujian Medical University and 30 healthy subjects were
also enrolled as the control group. Ficoll and Percoll density gradient
centrifugation separated of peripheral blood monocyte. Monocyte TF mRNA
expression was detected using reverse transcriptase-polymerase chain reaction (RT
PCR). RESULTS: There were significant differences in different stages of the
cancer (P < .05) and no significance among the histopathologic types (P > .05)
for the expression of monocyte TF mRNA in NSCLC patients, its expression was
significantly higher in cancer with lymph node metastasis than those without
lymph node metastasis (P < .01). Meanwhile, in NSCLC patients with VTE, the
expression of monocyte TF mRNA was significantly higher than that in patients
without VTE (P < .01). Difference of the survival curves between the low monocyte
TF mRNA expression and the high monocyte TF mRNA expression was significant (Log
rank x2 = 4.923, P < .05). CONCLUSIONS: Monocyte TF may be a relevant source of
TF-mediated thrombogenicity in NSCLC patients and may be associated with
prognosis in NSCLC.
PMID- 28419723
TI - Characteristics and outcomes of ALK+ non-small cell lung cancer patients in
Korea.
AB - AIM: This study aimed to describe characteristics, treatment patterns and
survival among Korean patients diagnosed with locally advanced or metastatic
anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC). METHODS: A
retrospective patient chart review was conducted in major cancer centers in Korea
in 2014-2015. Participating physicians reviewed patient charts and reported
characteristics, treatment patterns, clinician-defined progression-free survival
(PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC
patients. PFS and OS were estimated using Kaplan-Meier analysis. RESULTS:
Physicians reported on 55 ALK+ NSCLC patients. Median age at locally advanced or
metastatic NSCLC diagnosis was 60 years. Most patients (82%) received initial
chemotherapy; 13% received an ALK inhibitor in the first line; 62% received an
ALK inhibitor by the end of follow-up. Of the 30 patients who received
crizotinib, 83% discontinued and 13% died during crizotinib therapy. Median PFS
on crizotinib was 6.7 months. Of those who discontinued, 32% switched to
chemotherapy, 16% switched to a different ALK inhibitor and 52% received no
further therapy. After discontinuing crizotinib, median OS was 6.0 months
overall, and 3.4 months among patients who did not receive a second-generation
ALK inhibitor. CONCLUSION: In this study of locally advanced or metastatic ALK+
NSCLC patients in Korea, roughly one-third did not receive an ALK inhibitor.
Among patients who discontinued crizotinib, over half received no further
antineoplastic therapy and OS was poor, particularly among patients without
second-generation ALK inhibitor use. These findings suggest a need for greater
access to effective treatments following crizotinib discontinuation for ALK+
NSCLC patients in Korea.
PMID- 28419724
TI - A Reversed Photosynthesis-like Process for Light-Triggered CO2 Capture, Release,
and Conversion.
AB - Materials for CO2 capture have been extensively exploited for climate governance
and gas separation. However, their regeneration is facing the problems of high
energy cost and secondary CO2 contamination. Herein, a reversed photosynthesis
like process is proposed, in which CO2 is absorbed in darkness while being
released under light illumination. The process is likely supplementary to natural
photosynthesis of plants, in which, on the contrary, CO2 is released during the
night. Remarkably, the material used here is able to capture 9.6 wt.% CO2
according to its active component. Repeatable CO2 capture at room temperature and
release under light irradiation ensures its convenient and cost-effective
regeneration. Furthermore, CO2 released from the system is successfully converted
into a stable compound in tandem with specific catalysts.
PMID- 28419725
TI - Healthcare Costs and Medication Adherence Among Patients with Fibromyalgia:
Combination Medication vs. Duloxetine, Milnacipran, Venlafaxine, and Pregabalin
Initiators.
AB - OBJECTIVE: To examine medication adherence and healthcare costs for combination
prescription initiators (duloxetine/milnacipran/venlafaxine with pregabalin) vs.
monotherapy initiators (duloxetine, milnacipran, venlafaxine, and pregabalin)
among patients with fibromyalgia syndrome (FMS). METHODS: Our retrospective
cohort study used claims data for the South Carolina Blue Cross Blue Shield State
Health Plan (SHP). Patients with FMS >= 18 years of age, with prescription
initiation from July 1, 2007, through June 30, 2010, and SHP enrollment for 12
months pre- and post-index periods were included (combination: n = 100;
pregabalin: n = 665; duloxetine: n = 713; milnacipran: n = 131; venlafaxine: n =
272). Medication adherence measures included high adherence (medication
possession ratio >= 80%) and total supply days. Healthcare costs comprised direct
medical expenditures. Propensity score methods of inverse probability of
treatment weights were used to control for selection bias due to differing pre
index characteristics. RESULTS: Odds ratios for high adherence were significantly
increased (P < 0.05) among the combination cohort vs. the venlafaxine (2.15),
duloxetine (1.39), and pregabalin (2.20) cohorts. Rate ratios for total supply
days were significantly higher (P < 0.05) for combination vs. venlafaxine (1.23),
duloxetine (1.08), and pregabalin (1.32) cohorts. Expenditures for total health
care were significantly higher (P < 0.05) for combination vs. duloxetine ($26,291
vs. $17,190), milnacipran ($33,638 vs. $22,886), and venlafaxine ($26,586 vs.
$16,857) cohorts. CONCLUSIONS: Medication adherence was considerably better for
combination prescription initiators; however, expenditures for total health care
were higher. Still, our findings suggest important clinical benefits with the use
of combination prescription therapy, and prospective studies of medication
adherence are warranted to examine causal relationships with outcomes not
captured by healthcare claims databases.
PMID- 28419726
TI - Chemotaxonomic characterisation of the thaumarchaeal lipidome.
AB - Thaumarchaeota are globally distributed and abundant microorganisms occurring in
diverse habitats and thus represent a major source of archaeal lipids. The scope
of lipids as taxonomic markers in microbial ecological studies is limited by the
scarcity of comparative data on the membrane lipid composition of cultivated
representatives, including the phylum Thaumarchaeota. Here, we comprehensively
describe the core and intact polar lipid (IPL) inventory of ten ammonia-oxidising
thaumarchaeal cultures representing all four characterized phylogenetic clades.
IPLs of these thaumarchaeal strains are generally similar and consist of membrane
spanning, glycerol dibiphytanyl glycerol tetraethers with monoglycosyl,
diglycosyl, phosphohexose and hexose-phosphohexose headgroups. However, the
relative abundances of these IPLs and their core lipid compositions differ
systematically between the phylogenetic subgroups, indicating high potential for
chemotaxonomic distinction of thaumarchaeal clades. Comparative lipidomic
analyses of 19 euryarchaeal and crenarchaeal strains suggested that the lipid
methoxy archaeol is synthesized exclusively by Thaumarchaeota and may thus
represent a diagnostic lipid biomarker for this phylum. The unprecedented
diversity of the thaumarchaeal lipidome with 118 different lipids suggests that
membrane lipid composition and adaptation mechanisms in Thaumarchaeota are more
complex than previously thought and include unique lipids with as yet unresolved
properties.
PMID- 28419727
TI - Endotoxin testing of a wound debridement device containing medicinal Lucilia
sericata larvae.
AB - Alimentary products of medicinal Lucilia sericata larvae are studied to determine
their mechanisms of action, particularly in the contexts of wound debridement and
disinfection. Furthermore, the larvae can be applied to patients in contained
medical devices (such as the BioBag; BioMonde). Here, we tested the materials and
larval content of the most commonly used debridement device (the "BB-50") to
explore the possibility that endotoxins may be contributing to the bio-activity
of the product, given that endotoxins are potent stimulants of cellular
activation. Using standardised protocols to collect larval alimentary products
(LAP), we proceeded to determine residual endotoxin levels in LAP derived from
the device, before and after the neutralisation of interfering enzymatic
activity. The debridement device and its associated larval content was not a
significant source of lipopolysaccharide (LPS) activity. However, it is clear
from these experiments that a failure to remove the confounding serine proteinase
activity would have resulted in spuriously high and erroneous results. The
residual LPS levels detected are unlikely to be active in wound healing assays,
following cross-referencing to publications where LPS at much higher levels has
been shown to have positive and negative effects on processes associated with
wound repair and tissue regeneration.
PMID- 28419728
TI - Temporal changes in cutaneous bacterial communities of terrestrial- and aquatic
phase newts (Amphibia).
AB - Animal-associated bacterial communities play essential roles for their host's
ecology, physiology and health. Temporal dynamics of these communities are poorly
understood, but might be of high relevance for amphibians with a well-expressed
biphasic biology of adults where the structure of their skin changes drastically
between the aquatic and terrestrial phases. Here, we investigated the temporal
dynamics of cutaneous bacterial communities of Lissotriton boscai and Triturus
marmoratus by monthly sampling populations from a pond and surrounding
terrestrial habitats near A Coruna, Spain. These communities were characterized
by 16S rRNA gene amplicons from DNA isolated from skin swabs. Newt bacterial
communities displayed variation at three levels: between larvae and aquatic
adults, between adult life phases (terrestrial versus aquatic), and temporally
within life phases. The skin bacterial communities tended to differ to a lesser
extent temporally and between larvae and adults, and more strongly between life
phases. Larvae had a higher proportion of reads associated with antifungal taxa
compared with adults, while no differences were found among adult life phases.
Terrestrial specimens exhibited the highest community diversity. The regular
transitions of adult newts between aquatic and terrestrial environments might
contribute to the diversity of their skin microbiota and could increase disease
resistance.
PMID- 28419729
TI - Prevalence and Predictors of Patient Nonadherence to Pharmacological Acute Pain
Therapy at Home After Day Surgery: A Prospective Cohort Study.
AB - BACKGROUND: Good adherence to prescribed analgesics can be crucial to suppress or
even prevent acute postoperative pain after day surgery. The aim of this study
was to analyze prevalence and predictors of analgesic nonadherence after day
surgery. METHODS: Elective patients scheduled for day surgery were prospectively
enrolled from November 2008 to April 2010. Outcome parameters were measured by
using questionnaire packages at 2 time points: 1 week preoperatively and 4 days
postoperatively. The primary outcome parameter was analgesic nonadherence.
Adherence was defined according to the patient's response to the questionnaire
item "analgesia use as prescribed": full adherence, "yes"; partial adherence,
"yes, sometimes"; nonadherence, "no." Bivariate and multivariate logistic
regression analyses were performed to identify predictors of analgesic
nonadherence. RESULTS: A total of 1,248 patients were included. The prevalence
rates of analgesic nonadherence and partial adherence were 21.6% and 20.0%,
respectively, in the total study population but dropped to 9.4% and 19.8%,
respectively, in patients with moderate to severe pain. Low postoperative pain
intensity and short duration of surgery were the most important predictors of
analgesic nonadherence. The most important preoperative predictors for analgesic
nonadherence were low preoperative pain intensity, low preoperative expectations
of pain, and low fear of short-term effects of surgery. CONCLUSION: Analgesic
nonadherence and partial adherence are common after day surgery but decrease as
average pain intensity increases. Patients at risk for analgesic nonadherence can
be identified during the preoperative period based on preoperative pain
intensity, preoperative expectations of pain, and fear of surgery.
PMID- 28419730
TI - Low-Temperature Modification of ZnO Nanoparticles Film for Electron-Transport
Layers in Perovskite Solar Cells.
AB - An electron-transport layer (ETL) that selectively collects photogenerated
electrons is an important constituent of halide perovskite solar cells (PSCs).
Although TiO2 films are widely used as ETL of PSCs, the processing of TiO2 films
with high electron mobility requires high-temperature annealing and TiO2
dissociates the perovskite layer through a photocatalytic reaction. Here, we
report an effective surface-modification method of a room-temperature processed
ZnO nanoparticles (NPs) layer as an alternative to the TiO2 ETL. A combination of
simple UV exposure and nitric acid treatment effectively removes the hydroxyl
group and passivates surface defects in ZnO NPs. The surface modification of ZnO
NPs increases the power conversion efficiency (PCE) of PSCs to 14 % and decreases
the aging of PSCs under light soaking. These results suggest that the surface
modified ZnO film can be a good ETL of PSCs and provide a path toward low
temperature processing of efficient and stable PSCs that are compatible with
flexible electronics.
PMID- 28419731
TI - A qualitative study of doctors' and nurses' barriers to communicating with
seriously ill patients about their dependent children.
AB - OBJECTIVE: Research indicates that health personnel caring for seriously ill
patients with dependent children aged 0 to 18 years often avoid discussing with
them the challenges of being a family with a parent in treatment. Children of
seriously ill patients risk serious trauma and emotional difficulty later in life
and depend on adult support to minimize these consequences. Patients suffer
anxiety about supporting their children during their illness. Because of their
potentially pivotal role in supporting patients in enabling parent-child
communication, we examined HP's structural and emotional barriers to
communicating with patients about their children. METHODS: The study was based on
49 semi-structured, in-depth interviews with doctors and nurses working with
haematology, gynaecological cancer, and neurointensive care. Both interviews and
analysis addressed emotional and structural barriers, drawing on the theoretical
framework of Maturana's domains. RESULTS: The study found structural barriers
(eg, lack of space in the medical recording system, professional code, time
pressure, and lack of training) and emotional barriers (eg, the painful nature of
the situation and the perceived need of keeping professional distance). We found
that emotional barriers tended to grow when structural barriers were not
addressed. CONCLUSIONS: Our study indicates (1) the need to use templates and
manual procedures to gather and process information about children in medical
records; (2) the need for managerial backing for addressing children of seriously
ill patients and time spent on it; and (3) the need for future HP training
programmes to include how to implement procedures and how to address all
barriers.
PMID- 28419732
TI - A Phase 1 Randomized, Placebo-Controlled Study Assessing the Pharmacokinetics,
Safety, and Tolerability of Retosiban in Healthy, Nonpregnant Japanese Subjects.
AB - This study characterized the pharmacokinetics, safety, and tolerability of
retosiban in healthy, nonpregnant Japanese women prior to the enrollment of
Japanese women in preterm labor in phase 3 trials. This study had 2 cohorts.
Cohort 1 was a double-blind, sponsor-open, randomized study in Japanese women.
Cohort 2 was an open-label study in white women to compare the pharmacokinetics
with those of Japanese women. Retosiban was administered as a 6 mg/h infusion for
24 hours, followed by a 12 mg/h infusion over the next 24 hours; each infusion
was preceded by a 6 mg loading dose administered over 5 minutes. Plasma
concentrations of retosiban and its major metabolite, GSK2847065, were determined
with an informal comparison of pharmacokinetics between Japanese and white women.
There was minimal difference in exposure to retosiban or GSK2847065 between
Japanese and white women (ratio of 1.03 in retosiban AUC and Cmax ). The 2 doses
of retosiban were well tolerated across both populations, and no ethnic
difference was observed in the safety profile. Given the results of this study
and the known safety profile and dosing flexibility in the phase 3 trials, ethnic
specific dose adjustment of retosiban is not considered necessary for the
Japanese and general Asian population.
PMID- 28419733
TI - Interphotoreceptor matrix based biomaterial: Impact on human retinal progenitor
cell attachment and differentiation.
AB - While cell transplantation therapies show great promise as treatments for retinal
degeneration, the challenge of low cell survival upon transplantation motivates
exploration of materials that may serve as cell delivery vehicles and promote
survival and differentiation. In this study, we explored the native matrix that
surrounds the outer segments of photoreceptors and promotes their homeostasis,
interphotoreceptor matrix (IPM), as a substrate for human retinal progenitor
cells (hRPCs). Bovine IPM was characterized to determine its structure and
biochemical composition, and processed to develop substrates for cells. Cell
viability, morphology, proliferation and expression of photoreceptors marker
genes were studied on IPM-based substrates in vitro. We explored different
preparations of IPM as a scaffold. Lectin staining revealed that a distinct
honeycomb structure of native IPM is lost during centrifugation to prepare a more
concentrated suspension of matrix. Biochemical analysis of bovine IPM indicated
presence of glycosaminoglycans and proteins. IPM mediated hRPC attachment and
spreading with no signs of cytotoxicity. Cells proliferated more on native IPM
substrates compared to IPM that was centrifuged to create a concentrated
suspension. Cells cultured on IPM substrates expressed markers of photoreceptors:
rhodopsin, NRL and ROM1. Together this data supports further exploration of IPM
as a tool for retinal tissue engineering. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part B: Appl Biomater, 106B: 891-899, 2018.
PMID- 28419735
TI - Hospital use in Aboriginal and non-Aboriginal patients with chronic disease.
AB - OBJECTIVE: The objective of this study was to compare rates of hospital
utilisation in Aboriginal and non-Aboriginal peoples before and after hospital
admission for chronic obstructive pulmonary disease, heart failure and/or type 2
diabetes mellitus. METHODS: This was a longitudinal cohort study from 2002 to
2014, which was conducted in all hospitals in Western Australia. The participants
of this study were Aboriginal and non-Aboriginal patients with a principal
diagnosis of heart failure, type 2 diabetes or chronic obstructive pulmonary
disease, on admission to hospital, where such an event had not occurred in the
previous 3 years. Inpatient days and ED presentations were the main outcome
measures. RESULTS: Among the patients with chronic disease, Aboriginal people
have similar inpatient days for all causes compared to non-Aboriginal people.
However, they have much higher ED presentations in comparison. Age of onset of
cardinal events occurs 15-20 years earlier in Aboriginal patients with chronic
disease. Although age has little influence on ED presentations in non-Aboriginal
chronic disease patients, younger Aboriginal people with chronic disease present
far more often to ED than older Aboriginal people. CONCLUSIONS: Aboriginal people
use health services in a different manner when compared to non-Aboriginal people.
In a subset of patients with chronic disease, high use may be reduced with better
access to primary healthcare. Policy-makers and healthcare providers should
examine healthcare use from primary to tertiary care among the Aboriginal
population, with a particular focus on ED presentations; investigate the
underlying causes driving specific patterns of health service utilisation among
Aboriginal people; and develop interventions to reduce potential deleterious
impacts, and enhance the potential benefits, of specific patterns of healthcare
use.
PMID- 28419736
TI - Changes.
PMID- 28419734
TI - The life sulfuric: microbial ecology of sulfur cycling in marine sediments.
AB - Almost the entire seafloor is covered with sediments that can be more than 10 000
m thick and represent a vast microbial ecosystem that is a major component of
Earth's element and energy cycles. Notably, a significant proportion of microbial
life in marine sediments can exploit energy conserved during transformations of
sulfur compounds among different redox states. Sulfur cycling, which is primarily
driven by sulfate reduction, is tightly interwoven with other important element
cycles (carbon, nitrogen, iron, manganese) and therefore has profound
implications for both cellular- and ecosystem-level processes. Sulfur
transforming microorganisms have evolved diverse genetic, metabolic, and in some
cases, peculiar phenotypic features to fill an array of ecological niches in
marine sediments. Here, we review recent and selected findings on the microbial
guilds that are involved in the transformation of different sulfur compounds in
marine sediments and emphasise how these are interlinked and have a major
influence on ecology and biogeochemistry in the seafloor. Extraordinary
discoveries have increased our knowledge on microbial sulfur cycling, mainly in
sulfate-rich surface sediments, yet many questions remain regarding how sulfur
redox processes may sustain the deep-subsurface biosphere and the impact of
organic sulfur compounds on the marine sulfur cycle.
PMID- 28419737
TI - A 10-Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a
Hospital-wide Population of Patients Receiving Conventional Dosing: Is there
Enough Evidence for Suggesting TDM in the Majority of Patients?
AB - A retrospective study was conducted to assess our 10-year experience of
therapeutic drug monitoring (TDM) of linezolid in a large patient population to
establish whether conventional dosing may result in adequate drug exposure in the
majority of patients. Patients included in this study underwent TDM of linezolid
trough concentration (Cmin ) during treatment with conventional doses of 600 mg
every 12 hr in the period between January 2007 and June 2016. The desired range
of Cmin was set between 2 and 7 mg/L (underexposure, Cmin < 2 mg/L;
overexposure, Cmin > 7 mg/L). Multivariate logistic regression analysis
investigated variables potentially correlated with linezolid Cmin . One thousand
and forty-nine patients had 2484 linezolid Cmin assessed during treatment with
conventional doses. Median (IQR) linezolid Cmin was 5.08 mg/L (2.78-8.52 mg/L).
Linezolid Cmin was within the desired range in 50.8% of cases (1262/2484).
Overexposure (n = 821; 33%) occurred much more frequently than underexposure (n =
401; 16.2%) and was severe (>20 mg/L) in 3.9% of cases (98/2484). Linezolid
overexposure was significantly associated with CrCLC-G estimates <=40 mL/min. (OR
1.463; 95% CI 1.124-1.904, p = 0.005). Linezolid underexposure was significantly
associated with CrCLC-G estimates >100 mL/min. (OR 3.046; 95% CI 2.234-4.152, p <
0.001). Linezolid Cmin was not correlated linearly with CrCLC-G (R2 = 0.061).
Variability in renal function explained only partially the very wide
interindividual linezolid Cmin variability. Our study suggests that TDM could
represent a valuable approach in optimizing linezolid exposure in the majority of
patients.
PMID- 28419738
TI - Academic voice: On feminism, presence, and objectivity in writing.
AB - Academic voice is an oft-discussed, yet variably defined concept, and confusion
exists over its meaning, evaluation, and interpretation. This paper will explore
perspectives on academic voice and counterarguments to the positivist origins of
objectivity in academic writing. While many epistemological and methodological
perspectives exist, the feminist literature on voice is explored here as the
contrary position. From the feminist perspective, voice is a socially constructed
concept that cannot be separated from the experiences, emotions, and identity of
the writer and, thus, constitutes a reflection of an author's way of knowing. A
case study of how author presence can enhance meaning in text is included.
Subjective experience is imperative to a practice involving human interaction.
Nursing practice, our intimate involvement in patient's lives, and the nature of
our research are not value free. A view is presented that a visible presence of
an author in academic writing is relevant to the nursing discipline. The
continued valuing of an objective, colorless academic voice has consequences for
student writers and the faculty who teach them. Thus, a strategically used
multivoiced writing style is warranted.
PMID- 28419739
TI - Cardiac troponin T and fast skeletal muscle denervation in ageing.
AB - BACKGROUND: Ageing skeletal muscle undergoes chronic denervation, and the
neuromuscular junction (NMJ), the key structure that connects motor neuron nerves
with muscle cells, shows increased defects with ageing. Previous studies in
various species have shown that with ageing, type II fast-twitch skeletal muscle
fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres.
However, how this process is regulated is largely unknown. A better understanding
of the mechanisms regulating skeletal muscle fibre-type specific denervation at
the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac
troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component
of the mechanisms of muscle contraction. It is expressed in skeletal muscle
during early development, after acute sciatic nerve denervation, in various
neuromuscular diseases and possibly in ageing muscle. Yet the subcellular
localization and function of cTnT in skeletal muscle is largely unknown. METHODS:
Studies were carried out on isolated skeletal muscles from mice, vervet monkeys,
and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used
to analyse protein expression, real-time reverse transcription polymerase chain
reaction was used to measure gene expression, immunofluorescence staining was
performed for subcellular distribution assay of proteins, and electromyographic
recording was used to analyse neurotransmission at the NMJ. RESULTS: Levels of
cTnT expression in skeletal muscle increased with ageing in mice. In addition,
cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the
slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA)
RIalpha subunit was largely removed from, while PKA RIIalpha and RIIbeta are
enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch
muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i)
increased PKA RIalpha and reduced PKA RIIalpha at the NMJ; (ii) decreased the
levels of gene expression of muscle denervation markers; and (iii) enhanced
neurotransmission efficiency at NMJ. CONCLUSIONS: Cardiac troponin T at the NMJ
region contributes to NMJ functional decline with ageing mainly in the fast
twitch skeletal muscle through interfering with PKA signalling. This knowledge
could inform useful targets for prevention and therapy of age-related decline in
muscle function.
PMID- 28419740
TI - Pulmonary hypertension associated with combined fibrosing mediastinitis and
bronchial anthracofibrosis: A retrospective analysis in a single Chinese
hospital.
AB - INTRODUCTION: Both fibrosing mediastinitis (FM) and bronchial anthracofibrosis
(BAF) are unique diseases. The combined appearance of FM and BAF is extremely
rare. OBJECTIVES: The aim of this study was to investigate the clinical features
of patients with coexisting FM and BAF. METHOD: Between January 2003 and December
2015, a total of eight patients were diagnosed at the Peking Union Medical
College Hospital as having combined FM and BAF. The clinical presentations,
radiographic features and bronchoscopic findings of the eight patients were
reviewed. RESULTS: The patients were five women and three men with a median age
of 64 years (range 56-86 years). Symptoms included dyspnea (eight patients),
cough (seven patients), chest pain (two patients), hemoptysis (two patients) and
so on. Chest CT of all eight patients showed mediastinal soft-tissue lesions,
with multiple narrowed or obliterated lobar or segmental bronchi and arteries.
Bronchoscopy showed that all of the patients had multiple stenoses of lobar or
segmental bronchi with anthracotic pigmentation on the mucosa. Echocardiography
showed that all of the patients had elevated pulmonary arterial systolic pressure
(median 81 mm Hg, range 51-107 mm Hg). Each of the eight patients had a history
of exposure to, or infection with, tuberculosis, although there was no evidence
of active disease. All of the eight patients had long-term exposure to indoor
coal or biomass fuel smoke. CONCLUSIONS: FM can coexist with BAF, characterized
by prominent pulmonary hypertension. The possible etiological factors are
tuberculosis and coal or biomass fuel exposure.
PMID- 28419741
TI - Optimal treatment strategy for acute cholecystitis based on predictive factors:
Japan-Taiwan multicenter cohort study.
AB - BACKGROUND: Although early laparoscopic cholecystectomy is widely performed for
acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill
patients remains controversial. This study aims to determine the best practice
for the patients presenting with acute cholecystitis focused on disease severity
and comorbidities. METHODS: An international multicentric retrospective
observational study was conducted over a 2-year period. Patients were divided
into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy
after gallbladder drainage; Group C: gallbladder drainage alone; and Group D:
medical treatment alone. RESULTS: The subjects of analyses were 5,329 patients.
There were statistically significant differences in mortality rates between
patients with Charlson comorbidity index (CCI) scores below and above 6 (P <
0.001). The shortest operative time was observed in Group A patients who
underwent surgery 0-3 days after admission (P < 0.01). Multiple regression
analysis revealed CCI and low body mass index <20 as predictive factors of 30-day
mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and
respiratory dysfunction were predictive factors of 30-day mortality in Grade III
patients. In Grade III patients without predictive factors, there were no
difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A
patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%)
in cases with at least one predictive factor. CONCLUSION: Even patients with
Grade III severity, primary cholecystectomy can be performed safely if they have
no predictive factors of mortality. Gallbladder drainage may have a therapeutic
role in subgroups with higher CCI or higher disease severity.
PMID- 28419742
TI - A detachable laparoscopic bulldog clamp in laparoscopic-assisted colonoscopic
polypectomy - a video vignette.
PMID- 28419743
TI - Nonhealing ulcers on the scalp.
PMID- 28419744
TI - Establishment of an inferior vena cava filter database and interventional
radiology led follow-up - retrieval rates and patients lost to follow-up.
AB - INTRODUCTION: To evaluate the rates of inferior vena cava (IVC) filter retrieval
and the number of patient's lost to follow-up, before and after the establishment
of an IVC filter database and interventional radiology (inserting physician) led
follow-up. METHODS: On the 1st of June 2012, an electronic interventional
radiology database was established at our Institution. In addition, the
interventional radiology team took responsibility for follow-up of IVC filters.
Data were prospectively collected from the database for all patients who had an
IVC filter inserted between the 1st June 2012 and the 31st May 2014. Data on
patients who had an IVC filter inserted between the 1st of June 2009 to the 31st
of May 2012 were retrospectively reviewed. Patient demographics, insertion
indications, filter types, retrieval status, documented retrieval decisions, time
in situ, trackable events and complications were obtained in the pre-database (n
= 136) and post-database (n = 118) cohorts. RESULTS: Attempted IVC filter
retrieval rates were improved from 52.9% to 72.9% (P = 0.001) following the
establishment of the database. The number of patients with no documented decision
(lost to follow-up) regarding their IVC filter reduced from 31 of 136 (23%) to 0
of 118 patients (P = < 0.001). There was a non-significant reduction in IVC
filter dwell time in the post-database group (113 as compared to 137 days, P =
0.129). CONCLUSION: Following the establishment of an IVC filter database and
interventional radiology led follow-up, we demonstrate a significant improvement
in the attempted retrieval rates of IVC filters and the number of patient's lost
to follow-up.
PMID- 28419745
TI - Granulomatous variant of pigmented purpuric dermatosis: report of two cases and
review of the literature.
PMID- 28419746
TI - Factors for postoperative complications following pressure ulcer operation:
stepwise multiple logistic regression analysis.
AB - Patients with pressure ulcers are generally older, have a long hospital stay and
often have a variety of comorbidities. The decision to perform surgery for
pressure ulcer management can be difficult because of concerns about the risk of
postoperative complications. The aim of this study was to analyse the
relationship between comorbid conditions and surgical outcomes in order to guide
patient selection for pressure ulcer surgery. In 57 patients, data on age, defect
size, operating time, hospital stay, body mass index, surgical site, mobility
state, cardiac ischaemic history, diabetes, renal failure, ventilator dependency,
tracheostomy state, use of haemodilution therapy and cancer were evaluated using
stepwise multiple logistic regression analysis to determine the relationships
between variables. There were no postoperative cardiac ischaemic events. Wound
complications occurred in 8 patients (14%), pneumonia in 12 patients (21.1%) and
mortality in 1 patient (1.7%). The risk of postoperative pneumonia increased
1.069-fold in elderly patients (odds ratio = 1.069, P < 0.05) and increased 44.17
fold in preoperative ventilator users (odds ratio = 44.17, P < 0.05). The risk of
wound complication increased 1.012-fold with the presence of a larger defect site
(odds ratio = 1.012, P < 0.05) and increased 7.474-fold in patients who received
haemodilution therapy (odds ratio = 7.474, P < 0.05). Our results indicate that
most comorbid conditions did not significantly affect postoperative
cardiopulmonary or wound complications. However, the risk of postoperative
pneumonia increased in patients with ventilator use or old age, and the risk of
wound complication increased in patients with a large defect size and in those
who used haemodilution therapy.
PMID- 28419747
TI - A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough
QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in
Healthy Subjects.
AB - Daprodustat (GSK1278863) is a prolyl hydroxylase inhibitor in phase 3 clinical
studies for the treatment of anemia associated with chronic kidney disease. This
study was conducted to evaluate the effect of daprodustat on cardiac
repolarization and enrolled 55 healthy adult male (29) and female (26) subjects
who received single-dose 75 and 500 mg daprodustat, 400 mg moxifloxacin, and
placebo. Mean placebo-corrected change from baseline QT interval for daprodustat
showed no statistically significant increase. However, statistically significant
decreases in the DeltaDeltaQTcF were observed for both doses of daprodustat,
reaching a lowest value of -2.74 milliseconds for 75 mg and -5.93 milliseconds
for 500 mg daprodustat; this minor shortening effect is not considered clinically
significant. The moxifloxacin group showed a statistically significant increase
in the DeltaDeltaQTcF value, reaching a maximal increase of 11.47 milliseconds at
4 hours. Forty subjects (73%) reported at least 1 adverse event, with the highest
incidence with 500 mg daprodustat. This group had a higher incidence of
gastrointestinal adverse events compared to the other treatment groups. These
results suggest that 500 mg daprodustat was not well tolerated; however,
daprodustat at 75 mg was generally well tolerated. No new safety concerns were
identified in subjects who received 500 mg daprodustat.
PMID- 28419748
TI - The 'known' genetic potential for microbial communities to degrade organic
phosphorus is reduced in low-pH soils.
AB - In soil, bioavailable inorganic orthophosphate is found at low concentrations and
thus limits biological growth. To overcome this phosphorus scarcity, plants and
bacteria secrete numerous enzymes, namely acid and alkaline phosphatases, which
cleave orthophosphate from various organic phosphorus substrates. Using profile
hidden Markov modeling approaches, we investigated the abundance of various non
specific phosphatases, both acid and alkaline, in metagenomes retrieved from
soils with contrasting pH regimes. This analysis uncovered a marked reduction in
the abundance and diversity of various alkaline phosphatases in low-pH soils that
was not counterbalanced by an increase in acid phosphatases. Furthermore, it was
also discovered that only half of the bacterial strains from different phyla
deposited in the Integrated Microbial Genomes database harbor alkaline
phosphatases. Taken together, our data suggests that these 'phosphatase lacking'
isolates likely increase in low-pH soils and future research should ascertain how
these bacteria overcome phosphorus scarcity.
PMID- 28419749
TI - Novel 19 F-MRS beta-galactosidase reporter molecules incorporated nitrogen
mustard analogues.
AB - In this study, we propose a novel molecular platform-integrated fluorinated
antitumor nitrogen mustards for 19 F-MRS assay of beta-galactosidase (beta-gal)
activity. Following this idea, we have designed, synthesized, and characterized 2
fluoro-4-[bis(2'-chloroethyl)amino]phenyl beta-D-galactopyranoside 5, 2-fluoro-4
{bis[2'-O-(beta-D-galactopyranosyl)ethyl]amino}phenyl beta-D-galactopyranoside 8,
2-fluoro-4-{bis[[1"-(beta-D-galactopyranosyl)-1", 2", 3"-triazol-4"-yl]methyl]
amino}phenyl beta-D-galactopyranoside 14 and 2-fluoro-4-{bis[[1"-(beta-D
glucopyranosyl)-1", 2", 3"-triazol-4"-yl]methyl]amino}phenyl beta-D
galactopyranoside 15 through glycosylation and click reaction strategies, and
their structures were confirmed by NMR and HRMS or elemental analysis data. Among
them, 2-fluoro-4-[bis(2'-chloroethyl)amino]phenyl beta-D-galacto-pyranoside 5 was
found very sensitive to beta-gal (E801A) in PBS at 37 degrees C with big
DeltadeltaF response. Here, we demonstrated the feasibility of this platform for
assessing beta-gal activity in solution, and in vitro with lacZ-transfected human
MCF7 breast and PC3 prostate tumor cells, by the characterization of beta-gal
responsive 19 F-chemical shift changes DeltadeltaF and hydrolytic kinetics.
PMID- 28419750
TI - The effectiveness of virtual and augmented reality in health sciences and medical
anatomy.
AB - Although cadavers constitute the gold standard for teaching anatomy to medical
and health science students, there are substantial financial, ethical, and
supervisory constraints on their use. In addition, although anatomy remains one
of the fundamental areas of medical education, universities have decreased the
hours allocated to teaching gross anatomy in favor of applied clinical work. The
release of virtual (VR) and augmented reality (AR) devices allows learning to
occur through hands-on immersive experiences. The aim of this research was to
assess whether learning structural anatomy utilizing VR or AR is as effective as
tablet-based (TB) applications, and whether these modes allowed enhanced student
learning, engagement and performance. Participants (n = 59) were randomly
allocated to one of the three learning modes: VR, AR, or TB and completed a
lesson on skull anatomy, after which they completed an anatomical knowledge
assessment. Student perceptions of each learning mode and any adverse effects
experienced were recorded. No significant differences were found between mean
assessment scores in VR, AR, or TB. During the lessons however, VR participants
were more likely to exhibit adverse effects such as headaches (25% in VR P <
0.05), dizziness (40% in VR, P < 0.001), or blurred vision (35% in VR, P < 0.01).
Both VR and AR are as valuable for teaching anatomy as tablet devices, but also
promote intrinsic benefits such as increased learner immersion and engagement.
These outcomes show great promise for the effective use of virtual and augmented
reality as means to supplement lesson content in anatomical education. Anat Sci
Educ 10: 549-559. (c) 2017 American Association of Anatomists.
PMID- 28419751
TI - Clinical Characteristics of Fibromyalgia in a Chronic Pain Population.
AB - OBJECTIVE: To compare fibromyalgia (FM) characteristics among patients identified
in a community-based chronic pain cohort based on traditional International
Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of
patients identified using a novel predictive model. METHODS: This retrospective
study used data collected from July 1999 to February 17, 2015, in multiple
chronic pain clinics in the United States. Patients were assigned to the FM case
group based on specific inclusion criteria using ICD-9 codes or, separately, from
results of a novel FM predictive model that was developed using random forest and
logistic regression techniques. Propensity scoring (1:1) matched FM patients
(cases) to nonmalignant chronic pain patients without FM (controls). Patient
reported measures (eg, pain, fatigue, quality of sleep) and clinical
characteristics (ie, comorbidities, procedures, and regions of pain) were
outcomes for analysis. RESULTS: Nine ICD-9 clinical modification diagnoses had
odds ratios with large effect sizes (Cohen's d > 0.8), demonstrating the
magnitude of the difference between the FM and matched non-FM cohorts: chronic
pain syndrome, latex allergy, muscle spasm, fasciitis, cervicalgia, thoracic
pain, shoulder pain, arthritis, and cervical disorders (all P < 0.0001). Six
diagnoses were found to have a moderate effect size (Cohen's 0.5 < d > 0.8):
cystitis, cervical degeneration, anxiety, joint pain, lumbago, and cervical
radiculitis. CONCLUSIONS: The identification of multiple comorbidities,
diagnoses, and musculoskeletal procedures that were significantly associated with
FM may facilitate differentiation of FM patients from other conditions
characterized by chronic widespread pain. Predictive modeling may enhance
identification of FM patients who may otherwise go undiagnosed.
PMID- 28419752
TI - Surface orientation effects on bending properties of surgical mesh are
independent of tensile properties.
AB - INTRODUCTION: Current mechanical testing of surgical mesh focuses primarily on
tensile properties even though implanted devices are not subjected to pure
tensile loads. Our objective was to determine the flexural (bending) properties
of surgical mesh and determine if they correlate with mesh tensile properties.
METHODS: The flexural rigidity values of 11 different surgical mesh designs were
determined along three textile directions (machine, cross-machine, and 45 degrees
to machine; n = 5 for each) using ASTM D1388-14 while tracking surface
orientation. Tensile testing was also performed on the same specimens using ASTM
D882-12. Linear regressions were performed to compare mesh flexural rigidity to
mesh thickness, areal mass density, filament diameter, ultimate tensile strength,
and maximum extension. RESULTS: Of 33 mesh specimen groups, 30 had significant
differences in flexural rigidity values when comparing surface orientations (top
and bottom). Flexural rigidity and mesh tensile properties also varied with
textile direction (machine and cross-machine). There was no strong correlation
between the flexural and tensile properties, with mesh thickness having the best
overall correlation with flexural rigidity. CONCLUSIONS: Currently, surface
orientation is not indicated on marketed surgical mesh, and a single mesh may
behave differently depending on the direction of loading. The lack of correlation
between flexural stiffness and tensile properties indicates the need to examine
mesh bending stiffness to provide a more comprehensive understanding of surgical
mesh mechanical behaviors. Further investigation is needed to determine if these
flexural properties result in the surgical mesh behaving mechanically different
depending on implantation direction. (c) 2017 Wiley Periodicals, Inc. J Biomed
Mater Res Part B: Appl Biomater, 106B: 854-862, 2018.
PMID- 28419753
TI - Systematic Review of Gender Differences in Sepsis Management and Outcomes.
AB - PURPOSE: Contributors to disparities in sepsis management have been attributed to
genetic susceptibility, differences in clinical presentation, and healthcare
delivery. The influence of gender on survival or mortality of patients with
sepsis-related diagnoses is unclear. The purpose of the current study was to
systematically review published research to identify factors and outcomes
associated with sepsis management and outcomes based on gender differences.
METHODS: Covering a period from 2006 to 2016, a literature search was conducted
on four electronic data bases including the Cumulative Index to Nursing and
Allied Health Literature (CINAHL), EBSCO, MedlinePlus, and PubMed. Content
analysis of each article was performed independently by two authors. The
guidelines outlined in the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) Statement was the method used to assess the quality of
evidence of the articles in this review. FINDINGS: A full review was completed on
a total of 452 identified potentially relevant publications, and 7 publications
met inclusion criteria. The methodological approaches included prospective and
retrospective observational studies, and prospective and historical cohort
studies. The aim of these studies was to identify if gender differences exist
related to sepsis-related mortality, completion of Surviving Sepsis Campaign
resuscitation bundle elements, sepsis-related care processes, and sepsis-related
incidence and source. CONCLUSIONS: Clinical sepsis studies evaluating gender and
sepsis-related management and mortality are inconclusive and complex. Three
different outcomes exist: no difference, higher risk in females, or higher risk
in males. Further studies are needed to support the presence of gender
disparities on sepsis-related healthcare outcomes. CLINICAL RELEVANCE: Providers
should understand the importance of adhering to sepsis protocols and minimizing
treatment disparities including gender differences.
PMID- 28419754
TI - A field-based disparity analysis of new 1,2,5-oxadiazole derivatives endowed with
antiproliferative activity.
AB - A series of 1,2,5-oxadiazoles were synthesized as new potential antiproliferative
agents. The in vitro cytotoxic activity evaluation of title compounds through MTT
assay revealed that some of them showed significant activity against the HCT-116
cancer cell line. The field-based disparity analysis provided indications about
the electrostatic, hydrophobic, and shape features underlying the cytotoxicity,
suggesting that increasing the negative electrostatic field on the heterocyclic
core of the structure has positive effects on the activity. The structure
activity relationships (SAR) around a particular compound can be explained
allowing for a structural rationale for the differences in activity. The SAR
provided by this series of compounds can be exploited to carry out further lead
optimization.
PMID- 28419755
TI - A diagnostic algorithm for assessment of liver fibrosis by liver stiffness
measurement in patients with chronic hepatitis B.
AB - Steatosis could affect liver stiffness measurement in patients with nonalcoholic
fatty liver disease and chronic hepatitis C. In this study, we aimed to
investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)
infected patients and develop a diagnostic algorithm for prediction of liver
fibrosis by liver stiffness based on the controlled attenuation parameter. A
total of 488 HBV-infected patients who underwent clinical examination, Fibroscan
and liver biopsy were prospectively enrolled. The best liver stiffness
measurement (kPa) cut-offs for significant fibrosis (S>=3) and advanced fibrosis
(S>=4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter
cut-off for severe steatosis (>=30%) was 287 dB/m. Among patients with low-grade
fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in
subjects with severe steatosis or controlled attenuation parameter >=287 dB/m
compared with those without. Moreover, in subjects with low-grade fibrosis, a
higher rate of false-positive rate was observed in patients with severe steatosis
than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and
in patients with CAP>=287 dB/m compared with their counterpart (F0-F2: 23.7% vs
9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by
gamma-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of
0.17. In patients with GPR<0.17, similar results were observed. The presence of
steatosis may lead to overestimation of fibrosis assessed by liver stiffness
measurement in patient with chronic hepatitis B. A diagnostic algorithm for
assessing fibrosis using liver stiffness was developed by combining both
controlled attenuation parameter and GPR values.
PMID- 28419756
TI - Posterior ankle labral changes at MRI: A preliminary study.
AB - INTRODUCTION: The transverse ligament in the ankle joint has been described as a
labrum-like structure in a previous cadaveric study. The purpose of this study is
to assess the spectrum of abnormal changes related to this structure on
imaging/MRI, and correlate these findings with other ankle joint findings and
patient symptoms. METHOD: A retrospective observational review of 172 ankle MRI
scans was carried out independently by two fellowship trained musculoskeletal
Radiologists. Correlation between abnormal labral changes, other ankle joint
findings and patient symptomatology was performed. RESULTS: Abnormal labral
changes were seen in 26% of the MRI scans (n = 44/172) and included signal
change, contour abnormality with heterogeneous signal change, linear fluid filled
clefts, multidirectional fluid filled clefts, and a macerated labrum. There was a
statistically significant association between abnormal labral changes and the
presence of Stieda process/os trigonum (P = 0.001), talocrural joint
osteoarthritis (P = 0.0003), paralabral cysts (P = 0.0001), imaging features of
posterior impingement (P = 0.01), and both medial (P = 0.005) and lateral (P =
0.01) ankle ligament injuries. However, there was no statistically significant
association between abnormal labral changes and patient symptoms. CONCLUSION: The
posterior ankle labrum can develop a spectrum of abnormal MRI appearances in
patients with other ankle joint abnormalities. Although this study showed no
correlation between patients' symptoms and posterior ankle labral changes, larger
studies are needed to examine the biomechanical alterations that may arise from
these labral changes.
PMID- 28419757
TI - Social media and student engagement in anatomy education.
PMID- 28419758
TI - Provenance effect on carbon assimilation, photochemistry and leaf morphology in
Mediterranean Cistus species under chilling stress.
AB - The potential resilience of shrub species to environmental change deserves
attention in those areas threatened by climate change, such as the Mediterranean
Basin. We asked if leaves produced under different climate conditions through the
winter season to spring can highlight the leaf traits involved in determining
potential resilience of three Cistus spp. to changing environmental conditions
and to what extent intraspecific differences affect such a response. We analysed
carbon assimilation, maximum quantum efficiency of PSII photochemistry (Fv /Fm )
and leaf morphological control of the photosynthetic process in leaves formed
through the winter season into spring in C. creticus subsp. eriocephalus (CE), C.
salvifolius (CS) and C. monspeliensis (CM) grown from seed of different
provenances under common garden conditions. Intraspecific differences were found
in Fv /Fm for CE and CS. Carbon assimilation-related parameters were not affected
by provenance. Moreover, our analysis highlighted that the functional
relationships investigated can follow seasonal changes and revealed patterns
originating from species-specific differences in LMA arising during the
favourable period. Cistus spp. have great ability to modify the structure and
function of their leaves in the mid-term in order to cope with changing
environmental conditions. The Fv /Fm response to chilling reveals that
susceptibility to photoinhibition is a trait under selection in Cistus species.
Concerning carbon assimilation, differing ability to control stomatal opening was
highlighted between species. Moreover, seasonal changes of the functional
relationships investigated can have predictable consequences on species leaf
turnover strategies.
PMID- 28419760
TI - Bone marrow-derived stem/stromal cells and adipose tissue-derived stem/stromal
cells: Their comparative efficacies and synergistic effects.
AB - Mesenchymal stem cells (MSCs) are heterogeneous cell populations that serve as
reserves for tissue regeneration in the presence of disease or injury. Although
MSCs are found in various tissues, bone marrow-derived stem/stromal cells (BMSCs)
and adipose tissue-derived stem/stromal cells (ADSCs) have been most thoroughly
investigated. Furthermore, ADSCs have recently emerged as an attractive source of
MSCs due to their abundance and availability. BMSCs and ADSCs demonstrate similar
morphological characteristics, but their in vitro characteristics and
differentiation abilities appear to differ. In this review, the author summarizes
and compares current knowledge on BMSCs and ADSCs with particular emphasis on in
vitro expansion and osteogenic/angiogenic potential, and reviews knowledge of
their synergistic effects when co-applied. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part A: 105A: 2640-2648, 2017.
PMID- 28419761
TI - Pyoderma gangrenosum in Sjogren's syndrome and its successful treatment with
topical application of etanercept.
PMID- 28419759
TI - Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP
effector BerB.
AB - Knowledge about the molecular mechanisms that are involved in the regulation of
biofilm formation is essential for the development of biofilm-control measures.
It is well established that the nucleotide second messenger cyclic diguanosine
monophosphate (c-di-GMP) is a positive regulator of biofilm formation in many
bacteria, but more knowledge about c-di-GMP effectors is needed. We provide
evidence that c-di-GMP, the alternative sigma factor RpoN (sigma54), and the
enhancer-binding protein BerB play a role in biofilm formation of Burkholderia
cenocepacia by regulating the production of a biofilm-stabilizing
exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates
RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive
transcriptional regulator. An increased level of the BerA protein in turn induces
the production of biofilm-stabilizing exopolysaccharide in response to high c-di
GMP levels. Our findings imply that the production of biofilm exopolysaccharide
in B. cenocepacia is regulated through a cascade involving two consecutive
transcription events that are both activated by c-di-GMP. This type of regulation
may allow tight control of the expenditure of cellular resources.
PMID- 28419762
TI - Hobnail variant of papillary thyroid carcinoma: A case with an unusual
presentation.
AB - Variants of papillary thyroid carcinoma (PTC) account for up to 25% of the cases,
some of which are proven to be associated with aggressive clinical behavior such
as tall cell and columnar cell variants. Hobnail variant of PTC (HVPTC) is
recently described as a rare and aggressive variant of PTC. Herein, we are
reporting a case of HVPTC in a patient who presented with hemoptysis and an
intratracheal blood clot that was aspirated and submitted for cytopathological
examination. Cytomorphology displayed neoplastic cells with profound
micropapillary architecture, elongated nuclei, and prominent hobnail
configuration. Nuclear features of PTC such as pseudoinclusions, nuclear
overlapping, crowding, and grooves were readily identified. Subsequent total
thyroidectomy revealed a 1.4 cm PTC with columnar and hobnail components. HVPTC
is a rare locally aggressive subtype, which may present with metastasis from an
occult thyroid primary. HVPTC needs to be included in the differential diagnosis
of metastatic carcinoma with micropapillary architecture on fine needle
aspiration, particularly in head and neck area. Diagn. Cytopathol. 2017;45:754
756. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419763
TI - The effects of local cold application on fibromyalgia pain.
AB - AIM: This study was conducted to evaluate the effects of local cold application
on pain when applied to the trapezius muscles of patients with fibromyalgia.
METHOD: A one-group, pre-test/post-test, pre-experimental model was applied in
this study, which was conducted with 55 fibromyalgia patients who presented to a
rheumatology outpatient clinic. A 10-min cold application was administered to one
trapezius muscle of each patient. The participants' pain was evaluated, in total,
four times (before the cold application and 10 min, 1.5 h and 24 h after the cold
application). The visual analogue scale (VAS) for pain was used to collect data
for the study, and Friedman and Wilcoxon tests were used to assess the data.
RESULTS: The patients' pain mean score before (6.45, SD:1.27) the cold
applications was found to be significantly higher than the scores noted 10 min
(2.75, SD:1.73), 1.5 h (2.45, SD:1.29), and 24 h (3.36, SD:1.30) after the
application (P < 0.001). CONCLUSION: The study found that local cold applications
performed on the trapezius muscles of patients with fibromyalgia significantly
decreased their pain. With its discovery of a new method of pain control in
fibromyalgia patients, this study will significantly contribute to science and
will serve as a guide for pain management, especially in nursing practice.
Further studies to evaluate the maximum effect duration and effect mechanisms of
local cold applications to the trapezius muscles of FM patients are indicated.
PMID- 28419764
TI - Clinical application and verification of the TG13 diagnostic and severity grading
criteria for acute cholangitis: an international multicenter observational study.
AB - BACKGROUND: The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and
severity grading criteria for acute cholangitis. Subsequently updated in 2013,
the Tokyo Guidelines (TG13) have been widely adopted throughout the world as
global standard guidelines. We set out to verify the efficacy of these TG13
criteria in an international multicenter study. METHODS: We reviewed 6,063
patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan
over a 2-year period. The TG13 diagnostic and severity grading criteria were
retrospectively applied, and 30-day mortality was investigated. RESULTS: A
diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of
the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07
criteria. The 30-day mortality rates of patients with Grade III, Grade II, and
Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly
along with disease severity. The mortality rate in the 1,272 Grade II cases where
urgent or early biliary drainage was performed was 2.0% (n = 25), which was
significantly lower than that of 3.7% (n = 28) in the other 748 cases.
CONCLUSION: By using the TG13 diagnostic and severity grading criteria, more
patients with possible acute cholangitis can be diagnosed, and patients whose
prognosis can potentially be improved by early biliary drainage can be
identified. The TG13 criteria are appropriate and useful for clinical practice.
PMID- 28419766
TI - Microbial community function in the bleaching disease of the marine macroalgae
Delisea pulchra.
AB - Disease is increasingly viewed as a major factor impacting the health of both
natural and cultured populations of marine organisms, including macroalgae. The
red macroalga Delisea pulchra suffers from a bleaching disease resulting from
host stress and infection by opportunistic bacterial pathogens. However, how
pathogens cause the disease and how the entire macro algal-associated community
is involved in the process is unclear. Here, we perform a metagenomic analysis of
microbial communities associated with diseased and healthy D. pulchra across
multiple bleaching events. Analysis of reconstructed 16S rRNA gene sequences
showed that bacteria belonging to the families Rhodobacteraceae, Saprospiraceae
and Flavobacteriaceae, including bacteria previously implicated in algal
bleaching, to be enriched in diseased D. pulchra. Genes with predicted functions
related to chemotaxis, motility, oxidative stress response, vitamin biosynthesis
and nutrient acquisition were also prevalent in microbiomes of bleached algae,
which may have a role in pathogenicity. Reconstruction of genomes that were
abundant on bleached samples revealed that no single organism contains all
bleaching-enriched functional genes. This observation indicates that potential
virulence traits are distributed across multiple bacteria and that the disease in
D. pulchra may result from a consortium of opportunistic pathogens, analogous to
dysbiotic or polymicrobial diseases.
PMID- 28419765
TI - Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at
Enabling Safer and Earlier Translation of Biological Insights Into Human Testing.
PMID- 28419767
TI - Four New Diterpene Glucosides from Perovskia atriplicifolia.
AB - Four new diterpene glucosides, namely perovskiaditerpenosides A - D (1 - 4), were
isolated from the BuOH extract of Perovskia atriplicifolia. Their structures were
well elucidated by chemical methods and comprehensive spectroscopic analyses
including MS, IR, and NMR (1D and 2D). The newly isolated compounds were screened
for their cytotoxic activity against HepG2, NB4, HeLa, K562, MCF7, PC3, and HL60.
The obtained results indicated that the new compounds possessed considerable
cytotoxic activity.
PMID- 28419768
TI - Pneumatosis intestinalis related to jejunal feeding post-pancreaticoduodenectomy.
PMID- 28419769
TI - Nurse practitioner perceptions of barriers and facilitators in providing health
care for deaf American Sign Language users: A qualitative socio-ecological
approach.
AB - BACKGROUND AND PURPOSE: Nurse practitioners (NPs), as well as all healthcare
clinicians, have a legal and ethical responsibility to provide health care for
deaf American Sign Language (ASL) users equal to that of other patients,
including effective communication, autonomy, and confidentiality. However, very
little is known about the feasibility to provide equitable health care. The
purpose of this study was to examine NP perceptions of barriers and facilitators
in providing health care for deaf ASL users. DATA SOURCES: Semistructured
interviews in a qualitative design using a socio-ecological model (SEM).
CONCLUSIONS: Barriers were identified at all levels of the SEM. NPs preferred
interpreters to facilitate the visit, but were unaware of their role in assuring
effective communication is achieved. A professional sign language interpreter was
considered a last resort when all other means of communication failed. Gesturing,
note-writing, lip-reading, and use of a familial interpreter were all considered
facilitators. IMPLICATIONS FOR PRACTICE: Interventions are needed at all levels
of the SEM. Resources are needed to provide awareness of deaf communication
issues and legal requirements for caring for deaf signers for practicing and
student NPs. Protocols need to be developed and present in all healthcare
facilities for hiring interpreters as well as quick access to contact information
for these interpreters.
PMID- 28419770
TI - Pilot survey of the health of Massachusetts dentists.
AB - AIM: Dentistry is a career that is very rewarding because of the direct
opportunity to deliver essential health services to patients in need. Dentistry
is also very demanding; mentally, physically, and even emotionally. Little is
known about the health of dentists and how it compares to the health of the
general population. The aim of the present study was to report on the general
health and health practices of dentists in Massachusetts. METHODS: A medical
health and health practices survey was developed from the Delaware Valley
Community Health Center and customized. The surveys contained 36 questions
relating to demographics, general health, and health practices. RESULTS: A total
of 399 dentists completed the survey. Of those who responded to the survey, 78.2%
were males, 32.6% were 56-65 years of age, 23.1% were 66-75 years of age, and
21.6% were 46-55 years of age. CONCLUSION: This pilot study highlights several
health issues where dentists seem to have a lower incidence than the general
population: asthma, depression, diabetes, hearing loss, obesity, smoking, sleep
apnea, and thyroid disease. However, there are some health issues where dentists
have a higher incidence than the general population: taking at least one
prescription medication, gastroesophageal reflux disease, some form of cancer,
back pain, neck pain, headache, osteoarthritis, rheumatic arthritis, psoriatic
arthritis, and alcohol abuse.
PMID- 28419771
TI - Aspects of carotid structure and function in health and different stages of
chronic kidney disease.
AB - INTRODUCTION: Arterial remodelling and stiffening have been demonstrated in end
stage renal disease (ESRD). The presence of vascular alterations in earlier-stage
chronic kidney disease (CKD) is less studied. We evaluated vascular structure and
function in mild-to-moderate CKD (stages 2-3) compared with healthy subjects and
advanced CKD (stages 4-5). METHODS: Carotid ultrasound was performed in 103 non
dialysis CKD patients and 54 healthy controls. Carotid intima-media thickness
(CIMT) and common carotid artery (CCA) diameter were measured. Strain, stiffness
and the pressure-strain elastic modulus (Ep ) of the right CCA were calculated.
RESULTS: There was no significant difference in CCA diameter between CKD 2-3 and
controls. The CCA diameter was larger in CKD 4-5 compared with CKD 2-3 and
controls (CKD 4-5, 6.50 +/- 0.79 mm versus CKD 2-3, 6.08 +/- 0.56 mm, P = 0.003;
and versus controls 5.97 +/- 0.53 mm, P<0.001). However, after adjustments, the
difference in CCA diameter was valid only for older ages and also dependent on
systolic blood pressure (SBP). There were no significant differences in CIMT,
strain or stiffness between the groups, but Ep was higher in CKD 4-5 compared
with controls (P = 0.006). CONCLUSION: In mild-to-moderate CKD, there were no
significant differences in carotid artery structure or function compared with
healthy subjects. Only patients with advanced CKD and older ages showed signs of
arterial remodelling. Our study indicates that vascular alterations occur in
advanced CKD, with SBP and age as important contributing factors.
PMID- 28419772
TI - Visual memory uniquely predicts anhedonia in schizophrenia but not bipolar
disorder.
AB - OBJECTIVE: Deficits in memory have been suggested as an influential mechanism of
anhedonia, because while pleasant experiences may be enjoyed in-the-moment, the
cognitive processes involved in reporting anticipated or remembered enjoyable
experiences is thought to be impaired. This study will determine whether any
aspects of memory, including visual memory, verbal memory or working memory, are
significantly predictive of anhedonia in a sample of schizophrenia, psychotic
bipolar disorder and healthy controls. METHODS: The study included 38 individuals
with schizophrenia, 19 individuals with bipolar disorder with psychosis, and 43
age-matched healthy controls. All participants completed a self-report social and
physical anhedonia questionnaire along with a cognitive screening battery, which
assessed the domains of attention/vigilance, working memory, verbal learning,
visual learning, and reasoning and problem-solving. RESULTS: Anhedonia scores
were regressed onto domain scores to determine which areas of cognition uniquely
predicted level of anhedonia in each group. For the schizophrenia group, physical
anhedonia was significantly predicted by worse visual memory performance. The
regression models did not find significant cognitive predictors of physical or
social anhedonia in the bipolar disorder or control groups. CONCLUSIONS: This
study found a significant relationship between visual memory and physical
anhedonia in schizophrenia patients that was not present in a sample of psychotic
bipolar patients or healthy controls, adding to an accumulating body of evidence
that visual memory is related to anhedonia in schizophrenia. This relationship
may be explained by underlying abnormalities in the orbitofrontal cortex in
schizophrenia.
PMID- 28419773
TI - Non-invasive follicular neoplasm with papillary like nuclear features (NIFTP): If
it ain't broke, don't fix it. The cytopathologist's dilemma.
PMID- 28419774
TI - Double trouble: Concomitant infection of esophagus by Herpes and Candida in
diabetic, non HIV patients-Report of two cases.
PMID- 28419775
TI - Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum
Disorder.
AB - Autism is a complex genetic disorder where both de-novo and inherited genetics
factors play a role. Next generation sequencing approaches have been extensively
used to identify rare variants associated with autism. To date, all such studies
were focused on nuclear genome; thereby leaving the role of mitochondrial DNA
(mtDNA) variation in autism unexplored. Recently, analytical tools have been
developed to evaluate mtDNA in whole-exome data. We have analyzed the mtDNA
sequence derived from whole-exome sequencing in 10 multiplex families. In one of
the families we have identified two variants of interest in MT-ND5 gene that were
previously determined to impair mitochondrial function. In addition in a second
family we have identified two VOIs; mtDNA variant in MT-ATP6 and nuclear DNA
variant in NDUFS4, where both VOIs are within mitochondrial Respiratory Chain
Complex. Our findings provide further support for the role of mitochondria in ASD
and confirm that whole-exome sequencing allows for analysis of mtDNA, which sets
a stage for further comprehensive genetic investigations of the role of
mitochondria in autism. Autism Res 2017, 10: 1338-1343. (c) 2017 International
Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28419777
TI - MicroRNAs as biomarkers for psychiatric disorders with a focus on autism spectrum
disorder: Current progress in genetic association studies, expression profiling,
and translational research.
AB - MicroRNAs (miRNAs) are a group of small noncoding RNA molecules, 18-25
nucleotides in length, which can negatively regulate gene expression at the post
transcriptional level by binding to messenger RNAs. About half of all identified
miRNAs in humans are expressed in the brain and display regulatory functions
important for many biological processes related to the development of the central
nervous system (CNS). Disruptions in miRNA biogenesis and miRNA-target
interaction have been related to CNS diseases, including psychiatric disorders.
In this review, we focus on the role of miRNAs in autism spectrum disorder (ASD)
and summarize recent findings about ASD-associated genetic variants in miRNA
genes, in miRNA biogenesis genes, and miRNA targets. We discuss deregulation of
miRNA expression in ASD and functional validation of ASD-related miRNAs in animal
models. Including miRNAs in studies of ASD will contribute to our understanding
of its etiology and pathogenesis and facilitate the discrimination between
different disease subgroups. Autism Res 2017. (c) 2017 International Society for
Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1184-1203. (c) 2017
International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28419776
TI - The involuntary nature of binge drinking: goal directedness and awareness of
intention.
AB - Binge drinking represents a public health issue and is a known risk factor in the
development of alcohol use disorders. Previous studies have shown behavioural as
well as neuroanatomical alterations associated with binge drinking. Here, we
address the question of the automaticity or involuntary nature of the behaviour
by assessing goal-directed behaviour and intentionality. In this study, we used a
computational two-step task, designed to discern between model-based/goal
directed and model-free/habitual behaviours, and the classic Libet clock task, to
study intention awareness, in a sample of 31 severe binge drinkers (BD) and 35
matched healthy volunteers. We observed that BD had impaired goal-directed
behaviour in the two-step task compared with healthy volunteers. In the Libet
clock task, BD showed delayed intention awareness. Further, we demonstrated that
alcohol use severity, as reflected by the alcohol use disorders identification
test, correlated with decreased conscious awareness of volitional intention in
BD, although it was unrelated to performance on the two-step task. However, the
time elapsed since the last drinking binge influenced the model-free scores, with
BD showing less habitual behaviour after longer abstinence. Our findings suggest
that the implementation of goal-directed strategies and the awareness of
volitional intention are affected in current heavy alcohol users. However, the
modulation of these impairments by alcohol use severity and abstinence suggests a
state effect of alcohol use in these measures and that top-down volitional
control might be ameliorated with alcohol use cessation.
PMID- 28419778
TI - Single- and Multiple-Dose Pharmacokinetics of Once-Daily Formulations of
Raltegravir.
AB - A new once-daily formulation of raltegravir, an integrase strand transfer
inhibitor indicated in combination with other antiretroviral drugs for the
treatment of human immunodeficiency virus-1 infection, is under development.
Single-dose and steady-state pharmacokinetics of 1200 mg for 2 formulations of
raltegravir were characterized in 2 open-label phase 1 studies in healthy male
and female subjects aged 18 to 55 years. The new raltegravir 600-mg formulation
had a higher relative bioavailability compared with the 400-mg tablets. Once
absorbed, both 3 * 400-mg and 2 * 600-mg dosage forms of raltegravir exhibited
similar systemic pharmacokinetics; in dictating bioavailability, differences were
from increased absorption that was the result of improved in vivo
disintegration/dissolution. Food had a smaller effect on the pharmacokinetics of
raltegravir when given as 2 * 600-mg formulation (42% vs 73% decrease in AUC0
last ). Steady state was generally reached in 2 days, with little to no
accumulation with multiple-dose administration. Raltegravir 1200 mg was found to
exhibit pharmacokinetic properties amenable for once-daily dosing and was
generally well tolerated in healthy subjects after single and multiple doses. The
new formulation improved the bioavailability of this Biopharmaceutics
Classification System class II compound.
PMID- 28419779
TI - Validation of TG13 severity grading in acute cholecystitis: Japan-Taiwan
collaborative study for acute cholecystitis.
AB - BACKGROUND: The collaborative multicenter retrospective study of acute
cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was
evaluation of the clinical value of TG13 severity grading for AC. METHOD: The
study was designed as an international multicenter retrospective study of AC from
2011 to 2013. Based on the data, we investigated the TG13 severity grading by
analyzing the correlations between grade and prognosis, surgical procedures,
histopathology, and organ dysfunction and prognosis. RESULTS: An investigation
revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade
II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher
than lower grades (P < 0.001). The greater the number of organ dysfunction, the
higher the mortality rate (P < 0.001). However, the mortality rate varied
depending on the number of organ dysfunction (3.1-25%). With respect to the
surgical procedures, laparoscopic cholecystectomy was performed for Grade I
patients (P < 0.001), and the higher the grade, the more likely open surgery
would be selected (P < 0.001). CONCLUSION: TG13 severity grading criteria for AC
are providing great benefits in actual clinical settings. From this study, the
position of each severity grade was obviously confirmed.
PMID- 28419781
TI - Evaluation of stability of stereotactic space defined by cone-beam CT for the
Leksell Gamma Knife Icon.
AB - The Gamma Knife Icon comes with an integrated cone-beam CT (CBCT) for image
guided stereotactic treatment deliveries. The CBCT can be used for defining the
Leksell stereotactic space using imaging without the need for the traditional
invasive frame system, and this allows also for frameless thermoplastic mask
stereotactic treatments (single or fractionated) with the Gamma Knife unit. In
this study, we used an in-house built marker tool to evaluate the stability of
the CBCT-based stereotactic space and its agreement with the standard frame-based
stereotactic space. We imaged the tool with a CT indicator box using our CT
simulator at the beginning, middle, and end of the study period (6 weeks) for
determining the frame-based stereotactic space. The tool was also scanned with
the Icon's CBCT on a daily basis throughout the study period, and the CBCT images
were used for determining the CBCT-based stereotactic space. The coordinates of
each marker were determined in each CT and CBCT scan using the Leksell GammaPlan
treatment planning software. The magnitudes of vector difference between the
means of each marker in frame-based and CBCT-based stereotactic space ranged from
0.21 to 0.33 mm, indicating good agreement of CBCT-based and frame-based
stereotactic space definition. Scanning 4-month later showed good prolonged
stability of the CBCT-based stereotactic space definition.
PMID- 28419782
TI - Natural resource landscapes of a marine bacterium reveal distinct fitness
determining genes across the genome.
AB - Heterotrophic bacteria exploit diverse microhabitats in the ocean, from particles
to transient gradients. Yet the degree to which genes and pathways can contribute
to an organism's fitness on such complex and variable natural resource landscapes
remains poorly understood. Here, we determine the gene-by-gene fitness of a
generalist saprophytic marine bacterium (Vibrio sp. F13 9CS106) on complex
resources derived from its natural habitats - copepods (Apocyclops royi) and
brown algae (Fucus vesiculosus) - and as reference substrates, glucose and the
polysaccharide alginate, derived from brown algal cell walls. We find that
resource complexity strongly buffers fitness costs of mutations, and that
anabolic rather than catabolic pathways are more stringently required, likely due
to functional redundancy in the latter. Moreover, while carbohydrate-rich algae
requires several synthesis pathways, protein-rich Apocyclops does not, suggesting
this ancestral habitat for Vibrios is a replete medium with metabolically
redundant substrates. We also identify a candidate fitness trade-off for algal
colonization: deletion of mshA increases mutant fitness. Our results demonstrate
that gene fitness depends on habitat composition, and suggest that this
generalist uses distinct resources in different natural habitats. The results
further indicate that substrate replete conditions may lead to relatively relaxed
selection on catabolic genes.
PMID- 28419783
TI - High occurrence of Bathyarchaeota (MCG) in the deep-sea sediments of South China
Sea quantified using newly designed PCR primers.
AB - The archaeal phylum Bathyarchaeota, which is composed of a large number of
diverse lineages, is widespread and abundant in marine sediments. Environmental
factors that control the distribution, abundance and evolution of this largely
diversified archaeal phylum are currently unclear. In this study, a new pair of
specific primers that target the major marine subgroups of bathyarchaeotal 16S
rRNA genes was designed and evaluated to investigate the distribution and
abundance of Bathyarchaeota in marine sediments. The abundance of Bathyarchaeota
along two sediment cores from the deep-sea sediments of South China Sea (SCS,
each from the Dongsha and Shenhu area) was determined. A strong correlation was
found between the bathyarchaeotal abundance and the content of total organic
carbon (TOC), suggesting an important role of Bathyarchaeota in organic matter
remineralisation in the sediments of SCS. Furthermore, diversity analysis
revealed that subgroups Bathy-2, Bathy-8 and Bathy-10 were dominant
bathyarchaeotal members of the deep-sea sediments in the SCS. Bathy-8 was found
predominantly within the reducing and deeper sediment layers, while Bathy-10
occurred preferentially in the oxidizing and shallower sediment layers. Our study
lays a foundation for the further understanding of the ecological functions and
niche differentiation of the important but not well-understood sedimentary
archaeal group.
PMID- 28419784
TI - Four-Extremity Neurostimulation Using Two Cervical Octapolar Leads and High
Frequency of 10 kHz.
AB - OBJECTIVES AND METHODS: A few published reports describe successful clinical use
of low-frequency spinal cord stimulation (SCS) in the cervical spine resulting in
bilateral upper and lower extremity pain relief. A major side-effect when using
this modality of SCS is the uneven intensity of paresthesias, which are
frequently excessive in upper extremities while attempting to achieve optimal
paresthesia coverage in all 4 extremities. RESULTS AND CONCLUSIONS: Here we
describe a successful case of high-frequency SCS at 10 kHz where profound control
of neuropathic pain of all 4 extremities was achieved without the complication of
paresthesias. Discussed are future implications of such therapy.
PMID- 28419785
TI - Internal noise estimates correlate with autistic traits.
AB - Previous neuroimaging research has reported increased internal (neural) noise in
sensory systems of autistic individuals. However, it is unclear if this
difference has behavioural or perceptual consequences, as previous attempts at
measuring internal noise in ASD psychophysically have been indirect. Here, we use
a "gold standard" psychophysical double-pass paradigm to investigate the
relationship between internal noise and autistic traits in the neurotypical
population (n = 43). We measured internal noise in three tasks (contrast
perception, facial expression intensity perception, and number summation) to
estimate a global internal noise factor using principal components analysis. This
global internal noise was positively correlated with autistic traits (rs = 0.32,
P = 0.035). This suggests that increased internal noise is associated with the
ASD phenotype even in subclinical populations. The finding is discussed in
relation to the neural and genetic basis of internal noise in ASD. Autism Res
2017, 10: 1384-1391. (c) 2017 International Society for Autism Research, Wiley
Periodicals, Inc.
PMID- 28419786
TI - Toward the rational design of macrolide antibiotics to combat resistance.
AB - Macrolides, one of the most prescribed classes of antibiotics, bind in the
bacterial ribosome's polypeptide exit tunnel and inhibit translation. However,
mutations and other ribosomal modifications, especially to the base A2058 of the
23S rRNA, have led to a growing resistance problem. Here, we have used molecular
dynamics simulations to study the macrolides erythromycin and azithromycin in
wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli
ribosomes. We find that the ribosomal modifications result in less favorable
interactions between the base 2058 and the desosamine sugar of the macrolides, as
well as greater displacement of the macrolides from their crystal structure
position, illuminating the causes of resistance. We have also examined four
azithromycin derivatives containing aromatic indole-analog moieties, which were
previously designed based on simulations of the stalling peptide SecM in the
ribosome. Surprisingly, we found that the studied moieties could adopt very
different geometries when interacting with a key base in the tunnel, A751,
possibly explaining their distinct activities. Based on our simulations, we
propose modifications to the indole-analog moieties that should increase their
interactions with A751 and, consequently, enhance the potency of future
azithromycin derivatives.
PMID- 28419787
TI - Heisenberg strikes again.
AB - Systematic randomized clinical outcome data in BVS has largely been reported in
straightforward lesions, and BVS performance in more complex anatomy is not well
defined In this study, OCT-analysis of imaging outcomes in lesions with variable
degrees of calcification demonstrated similar acute performance between second
generation DES and BVS Open questions as to the unintended effect of OCT-guidance
on the results of the study as well as the longer-term clinical outcomes in these
lesions remain.
PMID- 28419788
TI - The Italian stallions of CLI "value care" delivery.
AB - Critical Limb ischemia with long segment occlusive disease typically reserved for
surgery can be treated with a high degree of success in expert centers via an
endovascular approach Nitinol woven stents appear to have high patency with
proper deployment in all PAD groups Increased early expense that is associated
with decreased re-intervention can be cost effective.
PMID- 28419789
TI - Overlapping bioresorbable scaffolds seems safe for now.
AB - Overlapping permanent scaffolds carries a long-term risk of target vessel failure
due to late malapposition and the development of neoatherosclerosis. Potentially,
overlapping bioresorbable scaffold (BRS) may lead to lower long-term risk. The
GHOST-EU registry reported similar short- and mid-term risks in patients with and
without BRS overlap. Larger size studies with longer follow-up are needed to
confirm the safety of BRS overlap.
PMID- 28419790
TI - The many radial access learning curves.
AB - The radial approach to endovascular procedures has a series of learning curves:
diagnostic heart catheterization, low-risk settings and "straightforward"
percutaneous coronary intervention, high-risk settings, and complex coronary
intervention, and peripheral vascular angiography and intervention. For
diagnostic and low-risk interventional procedures, incremental improvements in
technical success and safety are observed in the initial 200 procedures for most
operators compared to highly experienced operators. Formal didactic training and
ongoing support/review from an experienced radial operator(s) may expedite
surmounting the series of radial learning curves while maintaining optimal
procedural success and safety. Advances in technology and understanding will
require the most experienced radial operators to continually embrace their next
learning curve.
PMID- 28419791
TI - The role of rotational atherectomy in contemporary chronic total occlusion
percutaneous coronary intervention.
AB - Rotational atherectomy is performed infrequently (~3.5%) during chronic total
occlusion (CTO) percutaneous coronary intervention (PCI) for two indications:
treatment of balloon uncrossable and balloon undilatable lesions. Use of
rotational atherectomy in CTO PCI was associated with high success and acceptable
complication rates. Rotational atherectomy remains a "must have" device for
interventional cardiologists performing complex PCI.
PMID- 28419792
TI - Breaking the code: What is the best post-PCI MI definition?
AB - Various definitions of post-PCI MI have been recommended by different
professional societies and studies. This present study suggests that the troponin
based 3rd universal definition of post-PCI MI has prognostic value for recurrent
MI but not mortality alone, unlike the CK-MB based SCAI definition. Absent a
consensus on the best definition, clinical trials should report outcomes based on
multiple definitions of post-PCI MI.
PMID- 28419793
TI - Impact of emergency department discharge stream short stay unit performance and
hospital bed occupancy rates on access and patient flowmeasures: A single site
study.
AB - OBJECTIVE: The ED discharge stream short stay units (EDSSUs) aim to facilitate
patient flows through EDs. We investigate the relationship between EDSSU census
and hospital bed occupancy rates (BORs) on National Emergency Access Target
(NEAT) performance and did-not-wait (DNW) rates at a tertiary metropolitan adult
ED in Sydney, Australia. METHODS: We collated data for all ED presentations
between 1 January 2012 and 31 December 2014. Daily ED, EDSSU census and ED
accessible hospital BORs were tabulated with daily ED NEAT performance and DNW
rates. Non-parametric regression analyses was conducted on cohorts of
appropriate, inappropriate, successful and failed EDSSU admissions based on local
admission policies and BOR for NEAT and DNW outcomes. RESULTS: Among all
presentations (n = 192 506) during the study period, 43.8% of patients were
admitted in hospital including 10.4% for EDSSU (n = 20 081). Analyses reveal
modest positive correlation of EDSSU admissions with NEAT performance (tau =
0.35, P < 0.001) and weak negative correlation with DNW rates (tau = -0.29, P <
0.001). These associations were more pronounced on days when BOR >100% (tau =
0.39 and tau = -0.36, P < 0.001). BOR of >100% were associated with reduced EDSSU
admits, NEAT performance and increased DNW rates (P < 0.001). Appropriate EDSSU
admissions had shorter EDSSU length of stay than inappropriate EDSSU admissions
(350 vs 557 min, median difference -158 min, P < 0.001). CONCLUSION: Appropriate
use of EDSSU provides effective conduit for ongoing patients' management beyond
mandated timelines. Health systems should focus on reducing hospital BORs to
mitigate exclusive ED pressure to deliver NEAT performance targets.
PMID- 28419794
TI - [Healthy workplaces: a goal or a long-distance run?]
PMID- 28419795
TI - [Is it possible to improve the preventive usefulness of workers' health
surveillance in the current regulatory framework?]
AB - OBJECTIVE: In Spain, the limited preventive usefulness of health surveillance is
determined by the indiscriminate use of nonspecific "generic" health examinations
aimed at producing a "fitness for work list", presumably allowing companies to
comply with health and safety regulations. This study aimed to produce a
technical interpretation of the Spanish Prevention of Risks at Work Act and
propose a new conceptual framework to favour greater preventive usefulness of
health surveillance within the current regulatory framework. METHODS: Using
qualitative techniques of content analysis, the text of the Law was studied, the
key concepts that impeded the fulfilment of the preventive objectives of health
surveillance were identified, and a technical interpretation adjusted to
regulations was made in order to propose a new conceptual framework RESULTS: This
conceptual framework would include: clearly differentiating health surveillance
from health examinations (one of its instruments) and from fitness for work
evaluations (an independent concept in itself); restricting mandatory health
surveillance to situations in which it is "imperative" to carry it out because of
the existence of a substantial risk to workers or third parties, including
potentially vulnerable workers; and communicating the results of health
surveillance through preventive recommendations to the company, reserving fitness
for duty certificates -always based on clear, pre-established and justified
criteria in relation to risk- for mandatory surveillance. CONCLUSIONS: The
proposed new conceptual framework falls within the scope of the Spanish
Prevention of Risks at Work Act, and its implementation could contribute to
improving the preventive usefulness of health surveillance without the need to
reform the legislation.
PMID- 28419796
TI - [Third working conditions and health survey in Navarre, Spain: main findings].
AB - OBJECTIVE: To describe health problems and working conditions perceived by
workers of Navarra, Spain. METHODS: Conduct of the Third Survey of Working
Conditions and Health in Navarre. We administered the Seventh Spanish National
Survey of Working Conditions questionnaire by personal interviews conducted in
the workers' homes between October 2014 and December 2014, and using a three
stage stratified sampling approach, by economic activity, work establishment size
and gender. A total of 2744 interviews were completed, with a confidence level of
95.5% and P=Q, error +/- 1.99. The analysis was weighted by the sampling
variables. The results were summarized as percentages for qualitative variables
and point estimates for quantitative variables. RESULTS: Among the postivie
findings, 85% of respondents were well informed of job risks, 68% had access to a
health and safety representative, 50% underwent risk assessments and 60% received
periodic medical examinations. Among the notable self-reported occupational risk
factors were exposure to loud noise (16%), chemicals (33%), accident-prone
situations (76%), repetitive movements (62%), awkward postures (41%) and
biological agents (11%). Issues of concern include a high percentage of overtime
work (44% of men and 39% of women), feelings of being overworked (30.6% and
29.4%, respectively) and exposure to abusive behaviors (11.7% for verbal abuse),
especially among women, healthcare workers and teachers. The most prevalent
health problems were musculoskeletal (49% reporting back pain) and issues related
to work stress (20%). CONCLUSIONS: The current working conditions in Navarre
feature improved preventive services, persistence of traditional occupational
risk factors and emergence of new issues such as violence and work stressors.
PMID- 28419797
TI - [Alcohol consumption prevalence in civil servants].
AB - Alcohol consumption is a concern for its effects on health and repercussions on
the work environment. The objective of this study was to estimate the prevalence
of alcohol consumption among civil servants and to examine its association with
sociodemographic and occupational variables. A cross-sectional study was
conducted among 1180 workers from January to November 2011. The prevalence of
alcohol consumption was measured in ABV (alcohol by volume) units, and examined
by sociodemographic and occupational variables (sex, education level, type of
work and social class). Overall, 81.78%of the study population consumed alcohol;
most were men, with moderate-severe consumption levels. Alcohol consumption was
related to low education level, social class, and manual work. These results
indicate the need for occupational health services to implement preventive
actions at the workplace.
PMID- 28419798
TI - PVLOO-Based Training Set Selection Improves the External Predictability of
QSAR/QSPR Models.
AB - In QSAR/QSPR modeling, the indispensable way to validate the predictability of a
model is to perform its statistical external validation. It is common that a
division algorithm should be used to select training sets from chemical compound
libraries or collections prior to external validations. In this study, a division
method based on the posterior variance of leave-one-out cross-validation (PVLOO)
of the Gaussian process (GP) has been developed with the goal of producing more
predictive models. Four structurally diverse data sets of good quality are
collected from the literature and then redeveloped and validated on the basis of
training set selection methods, namely, four kinds of PVLOO-based training set
selection methods with three types of covariance functions (squared exponential,
rational quadratic, and neural network covariance functions), the Kennard-Stone
algorithm, and random division. The root mean squared error (RMSE) of external
validation reported for each model serves as a basis for the final comparison.
The results of this study indicate that the training sets with higher values of
PVLOO have statistically better external predictability than the training sets
generated from other division methods discussed here. These findings could be
explained by proposing that the PVLOO value of GP could indicate the mechanism
diversity of a specific compound in QSAR/QSPR data sets.
PMID- 28419799
TI - Synthesis of Protected 3-Deoxy-3-fluoro- and 4-Deoxy-4-fluoro-d
galactopyranosides from Levoglucosan.
AB - Fluorinated carbohydrates are invaluable tools to study various biochemical
processes. Herein, we describe a new strategy to access orthogonally protected 3
deoxy-3-fluorogalactopyranose and acetylated 4-deoxy-4-fluorogalactopyranose.
Starting from inexpensive levoglucosan, most reactions were performed on a gram
scale and allowed excellent regio- and stereocontrol with a minimal use of
protection/deprotection cycles. Hence, we developed practical alternatives to the
decade-long reported method to access both 3-deoxy-3-fluoro- and 4-deoxy-4
fluorogalactopyranose.
PMID- 28419800
TI - pH Reversible Encapsulation of Oppositely Charged Colloids Mediated by
Polyelectrolytes.
AB - We report the first example of reversible encapsulation of micron-sized particles
by oppositely charged submicron smaller colloids. The reversibility of this
encapsulation process is regulated by pH-responsive poly(acrylic acid) (PAA)
present in solution. The competitive adsorption between the small colloids and
the poly(acrylic acid) on the surface of the large colloids plays a key role in
the encapsulation behavior of the system. pH offers an experimental knob to tune
the electrostatic interactions between the two oppositely charged particle
species via regulation of the charge density of the poly(acrylic acid). This
results in an increased surface coverage of the large colloids by the smaller
colloids when decreasing pH. Furthermore, the poly(acrylic acid) also acts as a
steric barrier limiting the strength of the attractive forces between the
oppositely charged particle species, thereby enabling detachment of the smaller
colloids. Finally, based on the pH tunability of the encapsulation behavior and
the ability of the small colloids to detach, reversible encapsulation is achieved
by cycling pH in the presence of the PAA polyelectrolytes. The role of
polyelectrolytes revealed in this work provides a new and facile strategy to
control heteroaggregation behavior between oppositely charged colloids, paving
the way to prepare sophisticated hierarchical assemblies.
PMID- 28419801
TI - On-Surface Pseudo-High-Dilution Synthesis of Macrocycles: Principle and
Mechanism.
AB - Macrocycles have attracted much attention due to their specific "endless"
topology, which results in extraordinary properties compared to related linear
(open-chain) molecules. However, challenges still remain in their controlled
synthesis with well-defined constitution and geometry. Here, we report the
successful application of the (pseudo-)high-dilution method to the conditions of
on-surface synthesis in ultrahigh vacuum. This approach leads to high yields (up
to 84%) of cyclic hyperbenzene ([18]-honeycombene) via an Ullmann-type reaction
from 4,4"-dibromo-meta-terphenyl (DMTP) as precursor on a Ag(111) surface. The
mechanism of macrocycle formation was explored in detail using scanning tunneling
microscopy and X-ray photoemission spectroscopy. We propose that the dominant
pathway for hyperbenzene (MTP)6 formation is the stepwise desilverization of an
organometallic (MTP-Ag)6 macrocycle, which forms via cyclization of (MTP-Ag)6
chains under pseudo-high-dilution conditions. The high probability of cyclization
on the stage of the organometallic phase results from the reversibility of the C
Ag bond. The case is different from that in solution, in which cyclization
typically occurs on the stage of a covalently bonded open-chain precursor. This
difference in the cyclization mechanism on a surface compared to that in solution
stems mainly from the 2D confinement exerted by the surface template, which
hinders the flipping of chain segments necessary for cyclization.
PMID- 28419802
TI - Programming Post-Translational Control over the Metabolic Labeling of Cellular
Proteins with a Noncanonical Amino Acid.
AB - Transcriptional control can be used to program cells to label proteins with
noncanonical amino acids by regulating the expression of orthogonal aminoacyl
tRNA synthetases (aaRSs). However, we cannot yet program cells to control
labeling in response to aaRS and ligand binding. To identify aaRSs whose
activities can be regulated by interactions with ligands, we used a combinatorial
approach to discover fragmented variants of Escherichia coli methionyl tRNA
synthetase (MetRS) that require fusion to associating proteins for maximal
activity. We found that these split proteins could be leveraged to create ligand
dependent MetRS using two approaches. When a pair of MetRS fragments was fused to
FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were
introduced that direct substrate specificity toward azidonorleucine (Anl), Anl
metabolic labeling was significantly enhanced in growth medium containing
rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS
fragments to the termini of the ligand-binding domain of the estrogen receptor
yielded proteins whose Anl metabolic labeling was significantly enhanced when 4
hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest
that split MetRS can be fused to a range of ligand-binding proteins to create
aaRSs whose metabolic labeling activities depend upon post-translational
interactions with ligands.
PMID- 28419803
TI - Hydropersulfides: H-Atom Transfer Agents Par Excellence.
AB - Hydropersulfides (RSSH) are formed endogenously via the reaction of the gaseous
biotransmitter hydrogen sulfide (H2S) and disulfides (RSSR) and/or sulfenic acids
(RSOH). RSSH have been investigated for their ability to store H2S in vivo and as
a line of defense against oxidative stress, from which it is clear that RSSH are
much more reactive to two-electron oxidants than thiols. Herein we describe the
results of our investigations into the H-atom transfer chemistry of RSSH,
contrasting it with the well-known H-atom transfer chemistry of thiols. In fact,
RSSH are excellent H-atom donors to alkyl (k ~ 5 * 108 M-1 s-1), alkoxyl (k ~ 1 *
109 M-1 s-1), peroxyl (k ~ 2 * 106 M-1 s-1), and thiyl (k > 1 * 1010 M-1 s-1)
radicals, besting thiols by as little as 1 order and as much as 4 orders of
magnitude. The inherently high reactivity of RSSH to H-atom transfer is based
largely on thermodynamic factors; the weak RSS-H bond dissociation enthalpy (~70
kcal/mol) and the associated high stability of the perthiyl radical make the
foregoing reactions exothermic by 15-34 kcal/mol. Of particular relevance in the
context of oxidative stress is the reactivity of RSSH to peroxyl radicals, where
favorable thermodynamics are bolstered by a secondary orbital interaction in the
transition state of the formal H-atom transfer that drives the inherent
reactivity of RSSH to match that of alpha-tocopherol (alpha-TOH), nature's
premier radical-trapping antioxidant. Significantly, the reactivity of RSSH
eclipses that of alpha-TOH in H-bond-accepting media because of their low H-bond
acidity (alpha2H ~ 0.1). This affords RSSH a unique versatility compared to other
highly reactive radical-trapping antioxidants (e.g., phenols, diarylamines,
hydroxylamines, sulfenic acids), which tend to have high H-bond acidities.
Moreover, the perthiyl radicals that result are highly persistent under
autoxidation conditions and undergo very rapid dimerization (k = 5 * 109 M-1 s-1)
in lieu of reacting with O2 or autoxidizable substrates.
PMID- 28419804
TI - Simultaneous Reconstruction of the Medial and Lateral Collateral Ligaments for
Chronic Combined Ligament Injuries of the Ankle.
AB - BACKGROUND: Objective data on chronic injuries of the medial collateral ligament
(MCL) of the ankle are scarce. Chronic MCL injuries are frequently associated
with lateral collateral ligament (LCL) injuries. For patients with chronic
combined MCL and LCL injuries, the authors have performed simultaneous surgery of
the 2 ligaments. HYPOTHESIS: Simultaneous surgery of the 2 ligaments may be
effectively used to treat chronic combined MCL and LCL injuries. STUDY DESIGN:
Case series; Level of evidence, 4. METHODS: Surgical outcomes were evaluated in
29 consecutive patients presenting with chronic MCL and LCL injuries (30 ankles;
15 men and 14 women; mean age, 31 years; 13 competitive and 10 recreational
athletes). Preoperative and postoperative clinical outcomes were measured with
the Karlsson score and the Japanese Society for Surgery of the Foot (JSSF) ankle
hindfoot scale score. The patients underwent preoperative and postoperative
functional measurements and a radiological examination. In addition, preoperative
magnetic resonance imaging (MRI) results, arthroscopic findings, and histology of
the MCL were evaluated. RESULTS: Preoperatively, the deep fibers of the MCL did
not appear striated in 29 ankles, and high-intensity signal changes were observed
in 23 ankles on T2-weighted or gradient echo MRI. MCL ruptures were confirmed
with arthroscopic surgery. Medial impingement lesions and focal chondral lesions
were confirmed in 10 and 21 ankles, respectively. Histology of the reconstructed
MCL showed dense collagen fibers with vessels. The mean postoperative follow-up
period was 30 months (range, 24-52 months). There was a significant change
between preoperative and postoperative Karlsson scores (69.0 vs 96.1 points,
respectively; P < .0001) and JSSF scores (69.8 vs 94.5 points, respectively; P <
.0001). On varus and valgus stress radiography, the postoperative talar tilt
angle was significantly lower than the preoperative angle. Postoperative anterior
displacement on stress radiography was significantly lower than preoperative
anterior displacement. Postoperatively, all 23 athletes returned to their
preinjury level of sports participation. CONCLUSION: MCL insufficiency resulted
from medial ankle instability and medial impingement lesions. Outcomes in the
patients indicated that MCL reconstruction or resection of medial impingement
lesions, performed in addition to LCL reconstruction, is effective for treating
chronic combined MCL and LCL injuries of the ankle.
PMID- 28419805
TI - Hypoglossal Nerve Upper Airway Stimulator Implantation after Radiotherapy for
Head and Neck Malignancy.
PMID- 28419806
TI - Tracheal T-tubes for Long-term Management of the Unreconstructable Trachea in
Adults.
AB - Management of tracheostenosis in adult patients who are either medically
unreconstructable due to significant comorbidities or surgically
unreconstructable remains a challenge. The tracheal T-tube offers an excellent
permanent solution to the problem of the unreconstructable trachea. This article
reviews 3 patients who underwent tracheofissure and placement of a tracheal T
tube after failed prior attempts at repair of tracheal stenosis. The tracheal T
tubes have been maintained for 13, 15, and 36 years, and these patients have
enjoyed adequate phonatory and respiratory functions with the T-tube plugged and
functioning as an airway stent. There have been no major complications related to
use of the T-tube in this group of patients. The tracheal T-tube is a viable
alternative to long-term management of the unreconstructable trachea, allowing
patients airway support and adequate phonatory and respiratory function.
PMID- 28419807
TI - Otolaryngology Residency Program Research Resources and Scholarly Productivity.
AB - Objective To delineate research resources available to otolaryngology residents
and their impact on scholarly productivity. Study Design Survey of current
otolaryngology program directors. Setting Otolaryngology residency programs.
Subjects and Methods An anonymous web-based survey was sent to 98 allopathic
otolaryngology training program directors. Fisher exact tests and nonparametric
correlations were used to determine statistically significant differences among
various strata of programs. Results Thirty-nine percent (n = 38) of queried
programs responded. Fourteen (37%) programs had 11 to 15 full-time, academic
faculty associated with the residency program. Twenty (53%) programs have a
dedicated research coordinator. Basic science lab space and financial resources
for statistical work were present at 22 programs (58%). Funding is uniformly
provided for presentation of research at conferences; a minority of programs
(13%) only funded podium presentations. Twenty-four (63%) have resident research
requirements beyond the Accreditation Council for Graduate Medical Education
(ACGME) mandate of preparing a "manuscript suitable for publication" prior to
graduation. Twenty-five (67%) programs have residents with 2 to 3 active research
projects at any given time. None of the investigated resources were significantly
associated with increased scholarly output. There was no uniformity to research
curricula. Conclusions Otolaryngology residency programs value research,
evidenced by financial support provided and requirements beyond the ACGME
minimum. Additional resources were not statistically related to an increase in
resident research productivity, although they may contribute positively to the
overall research experience during training. Potential future areas to examine
include research curricula best practices, how to develop meaningful mentorship
and resource allocation that inspires continued research interest, and
intellectual stimulation.
PMID- 28419808
TI - Outcomes After 1-Stage Versus 2-Stage Revision Anterior Cruciate Ligament
Reconstruction.
AB - BACKGROUND: Revision anterior cruciate ligament reconstruction (ACLR) is becoming
increasingly common as the number of primary ACLR cases continues to rise.
Despite this, there are limited data on the outcomes of revision ACLR and even
less information specifically addressing the differences in 1-stage revision
reconstruction versus those performed in a 2-stage fashion after primary
reconstruction. PURPOSE: To compare the outcomes, patient satisfaction, and
failure rates of 1-stage versus 2-stage revision ACLR. STUDY DESIGN: Cohort
study; Level of evidence, 3. METHODS: All patients who underwent revision ACLR
between 2010 and 2014 by a single surgeon were collected, and skeletally mature
patients over the age of 17 years were included. Patients were excluded if they
were skeletally immature; had a previous intra-articular infection in the
ipsilateral knee; underwent a prior alignment correction procedure, cartilage
repair or transplant procedure, or meniscal allograft transplantation; or had an
intra-articular fracture. An ipsilateral or contralateral bone-patellar tendon
bone (BPTB) autograft was the graft of choice. A BPTB allograft was considered
for patients aged >=50 years, for any patient with an insufficient ipsilateral or
contralateral patellar tendon, or for those who chose not to have the
contralateral patellar tendon graft harvested. Patients completed a subjective
questionnaire preoperatively and at a minimum of 2 years postoperatively.
Magnetic resonance imaging and computed tomography of all knees were performed
preoperatively to assess for associated injuries and to evaluate the ACLR tunnel
size and location. Patients with malpositioned tunnels that would critically
overlap with an anatomically placed tunnel or those with tunnels >=14 mm in size
underwent bone grafting. RESULTS: A total of 88 patients met the inclusion
criteria for this study. There were 39 patients in the 1-stage revision surgery
group (19 male, 20 female) and 49 patients in the 2-stage revision surgery group
who underwent tunnel bone grafting first (27 male, 22 female). In both groups,
the 12-item Short Form Health Survey (SF-12) Physical Component Summary, Western
Ontario and McMaster Universities Arthritis Index, Lysholm, and Tegner activity
scale scores significantly improved from preoperatively to postoperatively. There
was no significant difference in the SF-12 Mental Component Summary score before
and after surgery in either group. Furthermore, there was no significant
difference in failure rates or other demographic data between the groups. We
observed 4 failures in the 1-stage reconstruction group (10.3%) and 3 failures in
the 2-stage reconstruction group (6.1%). CONCLUSION: In this study, objective
outcomes and subjective patient scores and satisfaction were not significantly
different between 1-stage and 2-stage revision ACLRs. Both groups had
significantly improved objective outcomes and patient subjective outcomes without
notable differences in failure rates. Further longitudinal studies comparing 1
stage and 2-stage revision ACLRs over a longer time frame are recommended.
PMID- 28419809
TI - Knee Biomechanics During Jogging After Arthroscopic Partial Meniscectomy: A
Longitudinal Study.
AB - BACKGROUND: Altered knee joint biomechanics is thought to play a role in the
pathogenesis of knee osteoarthritis and has been reported in patients after
arthroscopic partial meniscectomy (APM) while performing various activities.
Longitudinally, understanding knee joint biomechanics during jogging may assist
future studies to assess the implications of jogging on knee joint health in this
population. PURPOSE: To investigate knee joint biomechanics during jogging in
patients 3 months after APM and a healthy control group at baseline and 2 years
later at follow-up. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy
eight patients who underwent medial APM and 38 healthy controls underwent a 3
dimensional motion analysis during barefoot overground jogging at baseline. Sixty
four patients who underwent APM and 23 controls returned at follow-up. External
peak moments (flexion and adduction) and the peak knee flexion angle during
stance were evaluated for the APM leg, non-APM leg (nonoperated leg), and control
leg. RESULTS: At baseline, the peak knee flexion angle was 1.4 degrees lower in
the APM leg compared with the non-APM leg ( P = .03). No differences were found
between the moments in the APM leg compared with the control leg (all P > .05).
However, the normalized peak knee adduction moment was 35% higher in the non-APM
leg compared with the control leg ( P = .008). In the non-APM leg, the normalized
peak knee adduction and flexion moments were higher compared with the APM leg by
16% and 10%, respectively, at baseline ( P <= .004). Despite the increase in the
peak knee flexion moment in the APM leg compared with the non-APM leg ( P <
.001), there were no differences in the peak knee flexion moment or any other
parameter assessed at 2-year follow-up between the legs ( P > .05). CONCLUSION:
Comparing the APM leg and control leg, no differences in knee joint biomechanics
during jogging for the variables assessed were observed. Higher knee moments in
the non-APM leg may have clinical implications for the noninvolved leg. Kinematic
differences were small (~1.4 degrees ) and therefore of questionable clinical
relevance. CLINICAL RELEVANCE: These results may facilitate future clinical
research regarding the implications of jogging on knee joint health in middle
aged, overweight patients after APM.
PMID- 28419810
TI - The Relationship of Static Tibial Tubercle-Trochlear Groove Measurement and
Dynamic Patellar Tracking.
AB - BACKGROUND: The tibial tubercle to trochlear groove (TT-TG) distance is used for
screening patients with a variety of patellofemoral joint disorders to determine
who may benefit from patellar medialization using a tibial tubercle osteotomy.
Clinically, the TT-TG distance is predominately based on static imaging with the
knee in full extension; however, the predictive ability of this measure for
dynamic patellar tracking patterns is unknown. PURPOSE: To determine whether the
static TT-TG distance can predict dynamic lateral displacement of the patella.
STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: The static
TT-TG distance was measured at full extension for 70 skeletally mature subjects
with (n = 32) and without (n = 38) patellofemoral pain. The dynamic patellar
tracking patterns were assessed from approximately 45 degrees to 0 degrees of
knee flexion by use of dynamic cine-phase contrast magnetic resonance imaging.
For each subject, the value of dynamic lateral tracking corresponding to the
exact knee angle measured in the static images for that subject was identified.
Linear regression analysis determined the predictive ability of static TT-TG
distance for dynamic patellar lateral displacement for each cohort. RESULTS: The
static TT-TG distance measured with the knee in full extension cannot accurately
predict dynamic lateral displacement of the patella. There was weak predictive
ability among subjects with patellofemoral pain ( r2 = 0.18, P = .02) and no
predictive capability among controls. Among subjects with patellofemoral pain and
static TT-TG distances 15 mm or more, 8 of 13 subjects (62%) demonstrated neutral
or medial patellar tracking patterns. CONCLUSION: The static TT-TG distance
cannot accurately predict dynamic lateral displacement of the patella. A large
percentage of patients with patellofemoral pain and pathologically large TT-TG
distances may have neutral to medial maltracking patterns.
PMID- 28419811
TI - Augmentation of Distal Biceps Repair With an Acellular Dermal Graft Restores
Native Biomechanical Properties in a Tendon-Deficient Model.
AB - BACKGROUND: The majority of distal biceps tendon injuries can be repaired in a
single procedure. In contrast, complete chronic tears with severe tendon
substance deficiency and retraction often require tendon graft augmentation. In
cases with extensive partial tears of the distal biceps, a human dermal allograft
may be used as an alternative to restore tendon thickness and biomechanical
integrity. HYPOTHESIS: Dermal graft augmentation will improve load to failure
compared with nonaugmented repair in a tendon-deficient model. STUDY DESIGN:
Controlled laboratory study. METHODS: Thirty-six matched specimens were organized
into 1 of 4 groups: native tendon, native tendon with dermal graft augmentation,
tendon with an attritional defect, and tendon with an attritional defect repaired
with a graft. To mimic a chronic attritional biceps lesion, a defect was created
by a complete tear, leaving 30% of the tendon's width intact. The repair
technique in all groups consisted of cortical button and interference screw
fixation. All specimens underwent cyclical loading for 3000 cycles and were then
tested to failure; gap formation and peak load at failure were documented.
RESULTS: The mean (+/-SD) load to failure (320.9 +/- 49.1 N vs 348.8 +/- 77.6 N,
respectively; P = .38) and gap formation (displacement) (1.8 +/- 1.4 mm vs 1.6 +/
1.1 mm, respectively; P = .38) did not differ between the native tendon groups
with and without graft augmentation. In the tendon-deficient model, the mean load
to failure was significantly improved with graft augmentation compared with no
graft augmentation (282.1 +/- 83.8 N vs 199.7 +/- 45.5 N, respectively; P = .04),
while the mean gap formation was significantly reduced (1.2 +/- 1.0 mm vs 2.7 +/-
1.4 mm, respectively; P = .04). The mean load to failure of the deficient tendon
with graft augmentation (282.1 N) compared with the native tendon (348.8 N) was
not significantly different ( P = .12). This indicates that the native tendon did
not perform differently from the grafted deficient tendon. CONCLUSION: In a
tendon-deficient, complete distal biceps rupture model, acellular dermal
allograft augmentation restored the native tendon's biomechanical properties at
time zero. The grafted tissue-deficient model demonstrated no significant
differences in the load to failure and gap formation compared with the native
tendon. As expected, dermal augmentation of attritional tendon repair increased
the load to failure and stiffness as well as decreased displacement compared with
the ungrafted tissue-deficient model. Tendons with their native width showed no
statistical difference or negative biomechanical consequences of dermal
augmentation. CLINICAL RELEVANCE: Dermal augmentation of the distal biceps is a
biomechanically feasible option for patients with an attritionally thinned-out
tendon.
PMID- 28419812
TI - Defining Quality in Head and Neck Reconstruction.
AB - Microvascular free flap reconstruction has now become the standard of care in the
reconstruction of selected head and neck defects. Although uncommon, flap failure
is a catastrophic event that results in significant patient morbidity, extended
length of hospitalization, and increased cost. However, there is currently no
gold standard for measuring the quality of a reconstructive center. Structure and
process outcomes have recently been developed, but outcome measures are still
lacking. Areas for future research include preoperative nutrition, preoperative
flap planning, intraoperative fluid management, appropriate thromboembolism
prophylaxis, consistent perioperative antibiotic regimens, skilled ancillary
staff, and clear outcome measures for performance measurement.
PMID- 28419813
TI - Do Clinical Practice Guidelines Improve Quality?
AB - Controversy exists surrounding how to best define and assess quality in the
health care setting. Clinical practice guidelines (CPGs) have been developed to
improve the quality of medical care by highlighting key clinical recommendations
based on recent evidence. However, data linking CPGs to improvements in outcomes
in otolaryngology are lacking. Numerous barriers contribute to difficulties in
translating CPGs to improvements in quality. Future initiatives are needed to
improve CPG adherence and define the impact of CPG recommendations on the quality
of otolaryngologic care provided to our patients.
PMID- 28419814
TI - High-Intensity Focused Ultrasound for Treatment of Symptomatic Benign Thyroid
Nodules: A Prospective Study.
AB - Purpose To evaluate first-year efficacy and changes in pressure symptoms and
health-related quality of life (HRQOL) after ultrasonographically (US) guided
high-intensity focused ultrasound (HIFU) ablation of symptomatic benign thyroid
nodules. Materials and Methods After ethics approval and informed consent were
obtained, a prospective trial was conducted. Patients with a symptomatic benign
thyroid nodule were given a choice of HIFU treatment or active surveillance.
Clinical and US examinations, pressure symptom scores (visual analog scale), and
HRQOL questionnaires (short form-12 survey) were evaluated at baseline and at 3,
6, and 12 months. The primary outcome was change in nodule volume after 12
months. The percentage of change in nodule volume was defined as the baseline
volume minus the volume at 12 months divided by the baseline volume times 100.
Ablation success was defined as a reduction in volume of greater than 50%. Nodule
volume was compared by using the paired t test. Continuous variables were
compared by using the Mann-Whitney U test, and categorical variables were
compared by using chi2 tests. Results Twenty-two patients underwent HIFU and 22
underwent active surveillance. Mean age was 53.11 years (range, 28-76 years) and
55.19 years (range, 41-70 years), respectively. The ratio of men to women was
2:20 and 1:21, respectively. The 12-month mean volume reduction +/- standard
deviation in the HIFU group was significant (68.87% +/- 15.27 [range, 47.35%
94.89%], P < .001) but not in the surveillance group (-2.11% +/- 6.29 [range,
15.64% to 12.70%], P > .05). Preablation nodule volume was the only determinant
of ablation success (odds ratio, 1.877; 95% confidence interval [CI]: 1.085,
3.249; P = .024). At 12 months, patients in the HIFU group had less swelling (P <
.001), lower pressure symptom scores (P < .001), and higher physical composite
scores (P = .006). Physical composite scores significantly correlated with 6
month reduction in nodule size (r = 0.768; 95% CI: 0.660, 0.930; P < .001) and 12
month reduction in nodule size (r = 0.704; 95% CI: 0.680, 940; P < .001).
Conclusion HIFU ablation of symptomatic benign thyroid nodules not only induced
significant shrinkage but also improved pressure symptom scores and HRQOL
throughout a 12-month period. (c) RSNA, 2017.
PMID- 28419815
TI - Diagnostic Performance of and Breast Tissue Changes at Early Breast MR Imaging
Surveillance in Women after Breast Conservation Therapy.
AB - Purpose To investigate the diagnostic performance and tissue changes in early (1
year or less) breast magnetic resonance (MR) imaging surveillance in women who
underwent breast conservation therapy for breast cancer. Materials and Methods
This prospective study was approved by the institutional review board, and
written informed consent was obtained. Between April 2014 and June 2016, 414
women (mean age, 51.5 years; range, 21-81 years) who underwent 422 early
surveillance breast MR imaging examinations (median, 6.0 months; range, 2-12
months) after breast conservation therapy were studied. The cancer detection
rate, positive predictive value of biopsy, sensitivity, specificity, accuracy,
and area under the curve of surveillance MR imaging, mammography, and
ultrasonography (US) were assessed. Follow-up was also obtained in 95 women by
using positron emission tomography (PET)/computed tomography (CT). Background
parenchymal enhancement (BPE) changes in the contralateral breast were assessed
according to adjuvant therapy by using the McNemar test. Results Of 11 detected
cancers, six were seen at MR imaging only, one was seen at MR imaging and
mammography, two were seen at MR imaging and US, one was seen at mammography
only, and one was seen at PET/CT only. Three MR imaging-depicted cancers were
observed at the original tumor bed, and two MR imaging-depicted cancers were
observed adjacent to the original tumor. Among two false-negative MR imaging
diagnoses (two cases of ductal carcinoma in situ), one cancer had manifested as
calcifications at mammography without differentiated enhancement at MR imaging,
and the other cancer was detected at PET/CT, but MR imaging results were negative
because of marked BPE, which resulted in focal lesion masking. The positive
predictive value of biopsy and the sensitivity, specificity, accuracy, and area
under the curve for MR imaging were 32.1% (nine of 28), 81.8% (nine of 11), 95.1%
(391 of 411), 94.7% (400 of 422), and 0.88, respectively. The sensitivity of
surveillance MR imaging (81.8%; 95% confidence interval [CI]: 48.2%, 97.7%) was
higher than that of mammography (18.2%; 95% CI: 2.3%, 51.8%) and US (18.2%; 95%
CI: 2.3%, 51.8%), with an overlap in CIs. The BPE showed a significant decrease
in the group of patients who received adjuvant chemotherapy (43 BPE decreases and
four BPE increases) and the group of patients who received hormone therapy (55
BPE decreases and two BPE increases) (P < .0001 for both). Conclusion Early MR
imaging surveillance after breast conservation therapy can be useful in patients
who have breast cancer, with superior sensitivity compared with that of
mammography and US. The BPE tends to be decreased at short-term follow-up MR
imaging in patients who receive adjuvant therapy. (c) RSNA, 2017.
PMID- 28419816
TI - High Rate of Osteoarthritis After Osteochondritis Dissecans Fragment Excision
Compared With Surgical Restoration at a Mean 16-Year Follow-up.
AB - BACKGROUND: Osteochondritis dissecans (OCD) is a disorder of subchondral bone
that causes adverse effects on the overlying cartilage and commonly affects the
knee. The incidence of OCD and its long-term effect on the knee joint are
controversial. Hypothesis/Purpose: The purpose of this study was to (1) evaluate
the rate of osteoarthritis and knee arthroplasty in a population-based cohort of
patients with OCD lesions treated operatively and (2) evaluate factors that may
predispose patients to knee osteoarthritis and arthroplasty. The investigators
hypothesized that OCD lesions diagnosed after skeletal maturity and treatment
with fragment excision would be predictive of a diagnosis of osteoarthritis.
STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The investigators
identified 221 patients (mean +/- SD age, 26.1 +/- 13.6 years) with OCD lesions
treated operatively between 1976 and 2010 and followed for 16.3 +/- 11.4 years
(mean +/- SD) from diagnosis. Information related to the diagnosis, laterality of
lesion, details of treatment, and progression to osteoarthritis was obtained from
the medical record. Surgical treatment was classified as fragment excision,
fragment preservation (lesion drilling and/or fragment fixation), or chondral
defect grafting (osteochondral allograft or autograft). Factors predictive of
osteoarthritis and arthroplasty were examined. RESULTS: There were 134 patients
in the fragment excision group, 78 patients in the fragment preservation group,
and 9 patients in the chondral defect grafting group. In the fragment excision
group, the cumulative incidence of osteoarthritis was 12.0% at 5 years, 17.0% at
10 years, 26.0% at 15 years, 39.0% at 20 years, and 70% at 30 years. The
cumulative incidence of arthroplasty was 2.0% at 5 years, 4.0% at 10 years, 4.0%
at 15 years, 10.0% at 20 years, and 32.0% at 30 years. In the fragment
preservation group, the cumulative incidence of osteoarthritis was 3.0% at 5
years, 7.0% at 10 years, 16.0% at 15 years, 25.0% at 20 years, and 51% at 30
years. The cumulative incidence of arthroplasty was 0.0% at 5 years, 0.0% at 10
years, 3.0% at 15 years, 6.0% at 20 years, and 11.0% at 30 years. No patients in
the chondral defect grafting group developed osteoarthritis or underwent
arthroplasty. Body mass index (BMI) greater than 25 kg/m2 (hazard ratio [HR] 3.3;
95% CI, 1.6-7.0), older age at diagnosis (HR 4.9; 95% CI, 1.8-17.3), and fragment
excision (HR 2.3; 95% CI, 1.2-4.6) were predictive of osteoarthritis. CONCLUSION:
OCD patients treated with fragment excision have a high rate of osteoarthritis
and knee arthroplasty at long-term follow-up. In contrast, patients treated with
fragment preservation or chondral defect grafting have lower rates of
osteoarthritis and arthroplasty. BMI greater than 25 kg/m2, older age at
diagnosis, and fragment excision were predictive of osteoarthritis.
PMID- 28419818
TI - Local Group 2 Innate Lymphoid Cells Promote Corneal Regeneration after Epithelial
Abrasion.
AB - Corneal injuries and infections are the leading cause of blindness worldwide.
Thus, understanding the mechanisms that control healing of the damaged cornea is
critical for the development of new therapies to promptly restore vision. Innate
lymphoid cells (ILCs) are a recently identified heterogeneous cell population
that has been reported to orchestrate immunity and promote tissue repair in the
lungs and skin after injury. However, whether ILCs can modulate the repair
process in the cornea remains poorly understood. We identified a population of
cornea-resident group 2 ILCs (ILC2s) in mice that express CD127, T1/ST2, CD90,
and cKit. This cell population was relatively rare in corneas at a steady state
but increased after corneal epithelial abrasion. Moreover, ILC2s were maintained
and expanded locally at a steady state and after wounding. Depletion of this cell
population caused a delay in corneal wound healing, whereas supplementation of
ILC2s through adoptive transfer partially restored the healing process. Further
investigation revealed that IL-25, IL-33, and thymic stromal lymphopoietin had
critical roles in corneal ILC2 responses and that CCR2- corneal macrophages were
an important producer of IL-33 in the cornea. Together, these results reveal the
critical role of cornea-resident ILC2s in the restoration of corneal epithelial
integrity after acute injury and suggest that ILC2 responses depend on local
induction of IL-25, IL-33, and thymic stromal lymphopoietin.
PMID- 28419817
TI - Objectively Measured Physical Activity in Patients After Anterior Cruciate
Ligament Reconstruction.
AB - BACKGROUND: Returning to a healthy level of physical activity is among the most
commonly discussed clinical goals for patients recovering from anterior cruciate
ligament reconstruction (ACLR). However, physical activity has not been
objectively measured in this population. PURPOSE: To investigate differences in
the mean time (min/d) spent in moderate-to-vigorous physical activity (MVPA) as
well as the daily step count (steps/d) between patients who underwent ACLR and
matched controls. A second purpose was to investigate relationships between MVPA
and objective assessments of the daily step count and Tegner and Marx activity
scales. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS:
Physical activity was assessed using ActiGraph accelerometers in 33 participants
with a history of primary unilateral or bilateral ACLR (mean time from surgery,
27.8 +/- 17.5 months; range, 6-67 months) as well as in 33 healthy controls
(matched on age, sex, and activity level). Participants wore the accelerometer
for 7 days and completed the International Knee Documentation Committee
subjective form and the Tegner and Marx activity scales. Independent t tests were
used to determine differences in each dependent variable per group. RESULTS:
Patients who underwent ACLR spent less time in MVPA (ACLR: 79.37 +/- 23.95 min/d;
control: 93.12 +/- 23.94 min/d; P = .02) and had a lower daily step count (ACLR:
8158 +/- 2780 steps/d; control: 9769 +/- 2785 steps/d; P = .02) compared with
healthy matched controls. However, the Marx (ACLR median: 11.0 [interquartile
range (IQR), 7-14]; control median: 12.0 [IQR, 8-13]; P = .85) and Tegner (ACLR
median: 6.0 [IQR, 5-8]; control median: 7.0 [IQR, 6-8]; P = .12) scores did not
differ between the groups, and no relationships were observed between objectively
measured physical activity and scale measures ( P > .05), except for a moderate
relationship between the Tegner score and daily step count in the ACLR group ( r
= 0.36, P = .04). Only 24% of patients who underwent ACLR met the guideline of
10,000 steps per day compared with 42% of controls. CONCLUSION: Patients who
underwent ACLR spent less time in MVPA and had a lower daily step count compared
with highly matched controls (age, sex, and activity level) with no history of
knee injuries. This was true despite being similar in activity levels, which
brings into question the utility of the Tegner and Marx activity scales.
PMID- 28419819
TI - Path to Illness Intrusiveness: What Symptoms Affect the Life of People Living
With Multiple Sclerosis?
AB - OBJECTIVE: To determine the direct and indirect effects of physical, emotional,
and cognitive impairments on illness intrusiveness in people with multiple
sclerosis (MS). DESIGN: Secondary analysis of a cross-sectional data set
collected in 2008 to identify sex differences in people living with MS. SETTING:
Three MS clinics. PARTICIPANTS: A random sample (N=189) of women and men
diagnosed with MS after 1995 were recruited and evaluated in 2008. INTERVENTIONS:
Not applicable. MAIN OUTCOME MEASURE: Illness Intrusiveness Rating Scale (updated
version using Rasch analysis). RESULTS: Path analysis yielded a model that was
significant (nonnormed fit index, .9913; normed fit index, .9846) with adequate
fit of the data to the model (goodness of fit index, .9781; chi2=21.41; P=.2084).
The model explained 55% of the variance of illness intrusiveness. Only emotional
and physical aspects were represented in the model because no cognitive
impairment stayed after variable reduction. The model showed the complete
mediation effect of fatigue on the physical function variables. CONCLUSIONS: This
project brings new evidence toward the conceptualization of illness intrusiveness
as a construct allowing future interventions that wish to target illness
intrusiveness or disease impact to be designed. It also presented statistical
evidence of the importance of treating fatigue not only as a symptom but also as
a consequence of other impairments.
PMID- 28419820
TI - Community acquired infections among refugees leading to Intensive Care Unit
admissions in Turkey.
AB - OBJECTIVES: Data on the impact of refugees on Intensive Care Units (ICUs) are
lacking in the literature, in particular for community-acquired (CA) infectious
diseases, for which they are known to be at higher risk. We did a descriptive,
multicenter study to analyze CA infections among refugee patients requiring ICU
admission. METHODS: Inclusion criteria were adult refugee patients admitted to an
ICU due to CA infections. Anonymized data were collected between January 1, 2010
and December 30, 2015 across 10 referral centers. RESULTS: 29.885 patients were
admitted to the ICUs in the study period. 37 patients were included the study,
the majority were from Syria (n=31, 83.8%). Mean (SD) age of the patients was
45.92+/-20.16years. The 5-year prevalence rate was 123.8 per 100.000 patients in
the ICUs. All patients had at least one comorbid condition. Forty-nine CA
infections were diagnosed. The most common CA infection was pneumonia (49%)
followed by urinary-tract infections (16.3%). 21 patients (56.7%) hospitalized in
the ICU had trauma history. Mortality rate was high at 22 patients (59.5%) with 5
(22.7%) deaths directly attributed to CA infections. CONCLUSIONS: Refugees
presented to ICUs with CA infections similar to the host populations (pneumonia
and urinary-tract infections) but had high mortality rates (59.5%). It seems that
Turkish ICUs were not congested with the refugee patients' influx for CA
infections. More research needs to be done to better understand how to deliver
preventative and timely health care services to this group of patients.
PMID- 28419821
TI - Expression of the enzymatically active legumain-like cysteine proteinase TvLEGU-1
of Trichomonas vaginalis in Pichia pastoris.
AB - The legumain-like cysteine proteinase TvLEGU-1 from Trichomonas vaginalis plays a
major role in trichomonal cytoadherence. However, its structure-function
characterization has been limited by the lack of a reliable recombinant
expression platform to produce this protein in its native folded conformation.
TvLEGU-1 has been expressed in Escherichia coli as inclusion bodies and all
efforts to refold it have failed. Here, we describe the expression of the
synthetic codon-optimized tvlegu-1 (tvlegu-1-opt) gene in Pichia pastoris strain
X-33 (Mut+) under the inducible AOX1 promoter. The active TvLEGU-1 recombinant
protein (rTvLEGU-1) was secreted into the medium when tvlegu-1-opt was fused to
the Aspergillus niger alpha-amylase signal peptide. The rTvLEGU-1 secretion was
influenced by the gene copy number and induction temperature. Data indicate that
increasing tvlegu-1-opt gene copy number was detrimental for heterologous
expression of the enzymatically active TvLEGU-1. Indeed, expression of TvLEGU-1
had a greater impact on cell viability for those clones with 26 or 29 gene copy
number, and cell lysis was observed when the induction was carried out at 30
degrees C. The enzyme activity in the medium was higher when the induction was
carried out at 16 degrees C and in P. pastoris clones with lower gene copy
number. The results presented here suggest that both copy number and induction
temperature affect the rTvLEGU-1 expression in its native-like and active
conformation.
PMID- 28419822
TI - Inhibitory effects of losartan and azelnidipine on augmentation of blood pressure
variability induced by angiotensin II in rats.
AB - Increased blood pressure variability has been shown to be associated with
cardiovascular morbidity and mortality. Recently we reported that continuous
infusion of angiotensin II not only elevated blood pressure level, but also
increased blood pressure variability in a manner assumed to be independent of
blood pressure elevation in rats. In the present study, the effects of the
angiotensin type I receptor blocker losartan and the calcium channel blocker
azelnidipine on angiotensin II-induced blood pressure variability were examined
and compared with that of the vasodilator hydralazine in rats. Nine-week-old male
Wistar rats were subcutaneously infused with 240 pmol/kg/min angiotensin II for
two weeks without or with oral administration of losartan, azelnidipine, or
hydralazine. Blood pressure variability was evaluated using a coefficient of
variation of blood pressure recorded every 15min under an unrestrained condition
via an abdominal aortic catheter by a radiotelemetry system. Treatment with
losartan suppressed both blood pressure elevation and augmentation of systolic
blood pressure variability in rats infused with angiotensin II at 7 and 14 days.
Azelnidipine also inhibited angiotensin II-induced blood pressure elevation and
augmentation of blood pressure variability; meanwhile, hydralazine attenuated the
pressor effect of angiotensin II, but had no effect on blood pressure
variability. In conclusion, angiotensin II augmented blood pressure variability
in an angiotensin type 1 receptor-dependent manner, and azelnidipine suppressed
angiotensin II-induced augmentation of blood pressure variability, an effect
mediated by the mechanism independent of the blood pressure-lowering action.
PMID- 28419823
TI - Genetic aspects of auto-immune profiles of healthy chickens.
AB - Auto-antibody profiles binding liver antigens differed between chicken lines
divergently selected for specific antibody responses to SRBC, and were affected
by ageing suggesting both genetic and environmental effects. Presence and levels
of IgM and IgG antibodies binding chicken liver cell lysate (CLL) fragments in
plasma at 5 weeks of age from 10 individual full sibs and their parents from 5
Hsrbc and 5 Lsrbc line families was studied to reveal genetic relations. Non
genetic maternal effects were studied by comparing auto-antibody profiles of 36
weeks old hens from 2 other unrelated lines with the profiles from their chicks
at hatch. IgM and IgG antibodies from parents and progeny from both Hsrbc and
Lsrbc lines bound CLL fragments. Significant line and generation differences and
their interactions were found for both isotypes. Higher staining of CLL fragments
was usually found for Hsrbc line birds. Lines were clustered by auto-antibody
profiles, but staining by birds of both lines in both generations was very
individual for IgG and IgM. The current data with full sibs therefore not
supported a genetic basis for auto-antibody profiles. IgG but not IgM auto
antibody profiles of chicks correlated with maternal auto-antibody profiles. The
results suggest that the auto-antibody repertoire of healthy chickens is largely
stochastically initiated and may be affected by environmental challenges during
ageing, but genetic mechanisms may underlie staining intensity of individual
bound CLL fragments. The present results suggest that identification of fragments
or profiles to be used at early age for genetic selection for health traits is
not feasible yet. Secondly, the IgM profile of neonatal chickens seems non
organised independent of the maternal profile, but the neonatal IgG profile is
much more related with the maternal profile. Consequences of these findings for
disease susceptibility or breeding for optimal health are discussed.
PMID- 28419824
TI - Effect of risperidone on serum homocysteine levels in first-episode, drug-naive
patients with schizophrenia.
AB - Some studies have shown that homocysteine (Hcy) levels are increased in patients
with schizophrenia, and may be involved in its pathophysiology. The purpose of
this study was to investigate the effect of the atypical antipsychotic drug
risperidone on serum Hcy levels and to explore the relationship between the
changes in Hcy levels and the therapeutic outcome, which, to our best knowledge
have not been investigated. Fifty-six first-episode and drug-naive inpatients
with schizophrenia were assigned to a 12-week treatment regime with risperidone.
Clinical efficacy was determined with the Positive And Negative Syndrome Scale
(PANSS). Serum Hcy levels were measured by sandwich enzyme-linked immunosorbent
assay in schizophrenia patients before and after the 12-week treatment, and the
values were compared with those of fifty-six age- and gender- matched healthy
controls. Serum Hcy levels were significantly higher in first-episode and drug
naive patients than in control subjects (11.18+/-4.53 vs. 5.99+/-3.61MUmol/L,
F=37.195, df=1, p=1.73*10-8). Moreover, a significant positive correlation
between Hcy levels and PANSS negative sub-score was observed (r=0.515; p=4.81*10
5). Serum Hcy levels were significantly decreased in patients after risperidone
treatment (baseline: 11.18+/-4.53MUmol/L vs. post-treatment: 8.98+/-4.07MUmol/L,
t=3.857, p=3.034*10-4). At post-treatment, there was a significant negative
relationship between serum Hcy levels and PANSS negative sub-scores (r=-0.288,
p=0.032). High Hcy levels at the onset of psychosis suggests that it may
contribute to the pathogenesis of schizophrenia and is related to clinical
psychopathology. Serum Hcy levels were significantly decreased in schizophrenia
patients after risperidone treatment.
PMID- 28419825
TI - Conversion of Pregabalin to 4-Isobutylpyrrolidone-2.
AB - Solid-state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica,
Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4
isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation
was implemented to further our understanding of the factors affecting the
conversion process.
PMID- 28419826
TI - Melting Process of the Peritectic Mixture of Lidocaine and Ibuprofen Interpreted
by Site Percolation Theory Model.
AB - Eutectic mixtures are often used in the design and delivery of drugs. In this
study, we examined the peritectic mixture of lidocaine (LDC) and ibuprofen (IBP)
using differential scanning calorimetry, Raman spectroscopy, and microscopy. The
obtained phase diagram showed that as the mixture was heated, first LDC melted at
293 K, then IBP dissolved in the liquefied LDC at 310 K, and finally all
remaining crystals melted. In the 1H NMR spectra, the signals of the carboxyl
group in IBP and amide or amine group in LDC shifted to the low magnetic field in
the IBP/LDC mixtures, because of the intermolecular interaction between these
moieties. Using FTIR spectroscopy, the kinetic "reaction" order of the melting
process in the mixtures with excess LDC, equimolar, and excess IBP was determined
to be +1/2, -1/2, and 0, respectively. The 2 contacts between the liquidus line
and the higher melting line at 310 K at IBP molar fractions of 1/3 and of 2/3
were explained on the basis of the site percolation theory.
PMID- 28419827
TI - Antihyperglycemic, antioxidant activities of tucuma oil (Astrocaryum vulgare) in
alloxan-induced diabetic mice, and identification of fatty acid profile by gas
chromatograph: New natural source to treat hyperglycemia.
AB - The aim of the study was to investigate the effect of the oral administration of
tucuma oil (Astrocaryum vulgare) on glucose and insulin levels, oxidative status,
and pancreatic genotoxic parameters of alloxan-induced diabetic mice. The animals
were divided into four groups (n = 6 each): control/water; control/tucuma oil;
diabetic/water; diabetic/tucuma oil treated for 14 days with 5.0 mL kg-1 via oral
gavage. Gas chromatograph characterization demonstrated that oleic/elaidic fatty
acid is the most abundant component present in this oil, followed by palmitic and
stearic fatty acids. Our results demonstrated an increase (p < 0.05) in water and
food intake, blood glucose, thiobarbituric acid reactive species (TBARS) levels,
damage index, and frequency of damage; conversely body weight, insulin levels,
catalase (CAT) and superoxide dismutase (SOD) activities, and cell viability were
decreased in the diabetic/water group compared to the control/water group. The
treatment with tucuma oil prevented these alterations in the diabetic/tucuma oil
group compared to the diabetic/water group, and restored these parameters near to
the control/water group. In summary, our findings demonstrated that treatment
with tucuma oil causes a hypoglycemic effect improving insulin levels and
antioxidant/oxidant status, and has a protector effect against pancreatic damage
induced by oxidative stress in alloxan-induced diabetic mice.
PMID- 28419828
TI - Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of
Lonicera japonica in streptozotocin-induced diabetic rats.
AB - Hyperglycemia and dyslipidemia are classic features for diabetes mellitus (DM).
In this study, one fraction of the crude polysaccharides extracted from Lonicera
japonica flower buds (LJP) were investigated for its hypolipidaemic and
hypoglycaemic activities by means of streptozotocin (STZ)-induced diabetic rats.
Interestingly, after orally administrated with 800mg/kg body weight (B.W.) LJP
for 42 days, the food and water intake and the levels of sugar and insulin in
blood for the diabetic rats were drastically decreased, while the contents of
liver and skeletal muscle glycogen and the concentrations of hepatic pyruvate
kinase and hexokinase were obviously increased (p<0.01 or p<0.05). The levels of
total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterin
(LDL-C) and very-low-density lipoprotein-cholesterin (VLDL-C) were significantly
descended, while high-density lipoprotein-cholesterin (HDL-C) was significantly
ascended (p<0.01 or p<0.05). In addition, the oxidant stress in liver was
restored as well. The results suggested that LJP could be considered as an
ingredient of functional foods for diabetes, and this is the first report about
the hypoglycemic and hypolipidemic effects of the polysaccharides extracted from
Lonicera japonica.
PMID- 28419829
TI - Characterization of polyhydroxyalkanoates produced by Synechocystis salina from
digestate supernatant.
AB - The current commercial production of polyhydroxyalkanoates (PHA) is based on
heterotrophic bacteria, using organic carbon sources from crops. To avoid the
competition with food and feed production, cyanobacteria, metabolising PHA from
carbon dioxide can be used. This research focuses on the investigation of the
thermal and rheological properties of PHA polymers accumulated by Synechocystis
salina, which had been cultivated in digestate supernatant and a mineral medium.
The dried bacterial cells had a polymer content of 5.5-6.6%. The relevance of the
derived PHA polymers for the common melt polymer processing was correlated with
their molecular mass distribution as well as with their thermal and rheological
properties. The determined thermal and rheological properties showed that PHA
polymers accumulated by S. salina on digestate supernatant or mineral medium are
comparable with the commercial available poly(3-hydroxybutyrate). However, the
results showed that PHA polymers in general require modification before melt
processing to increase their stability in the molten state.
PMID- 28419830
TI - Creative cognition and dopaminergic modulation of fronto-striatal networks:
Integrative review and research agenda.
AB - Creative cognition is key to human functioning yet the underlying neurobiological
mechanisms are sparsely addressed and poorly understood. Here we address the
possibility that creative cognition is a function of dopaminergic modulation in
fronto-striatal brain circuitries. It is proposed that (i) creative cognition
benefits from both flexible and persistent processing, (ii) striatal dopamine and
the integrity of the nigrostriatal dopaminergic pathway is associated with
flexible processing, while (iii) prefrontal dopamine and the integrity of the
mesocortical dopaminergic pathway is associated with persistent processing. We
examine this possibility in light of studies linking creative ideation, divergent
thinking, and creative problem-solving to polymorphisms in dopamine receptor
genes, indirect markers and manipulations of the dopaminergic system, and
clinical populations with dysregulated dopaminergic activity. Combined, studies
suggest a functional differentiation between striatal and prefrontal dopamine:
moderate (but not low or high) levels of striatal dopamine benefit creative
cognition by facilitating flexible processes, and moderate (but not low or high)
levels of prefrontal dopamine enable persistence-driven creativity.
PMID- 28419831
TI - Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the
rat bed nucleus of the stria terminalis.
AB - The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in
the forebrain, composed of multiple sub-nuclei, each with discrete populations of
neurons. Progress in understanding BNST function, both in the adult and during
postnatal maturation, is dependent upon a more complete characterization of
neuronal phenotypes in the BNST. The aim of the current study was to define the
molecular phenotype of one postnatal BNST neuronal population, in order to
identify molecular factors that may underlie both (protein marker-related)
immaturity, and secondly, the transience of this phenotype. This BNST population
was originally identified by high, but transient expression of the EGR1
transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI).
The current results confirm a high level of Egr1 activation in postnatal day 10
(PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of
transient activation in female brains. Apparent cellular immaturity in this
population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3,
was found to be uncorrelated with both key neuronal regulator protein expression
(SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a
partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa
decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co
expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at
PN40. The transcriptional basis of the transient and partial catecholaminergic
phenotype was investigated by analysing TFs known to maintain adult dopaminergic
(TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack
forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons
had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear
receptor that is critical for adult maintenance of midbrain dopamine neurons.
These results detail the molecular features of an immature neuronal phenotype,
and reveal TF deficiencies that may underlie postnatal transience of the
phenotype.
PMID- 28419832
TI - Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2
pathway to alleviate ethanol-induced hepatic injury.
AB - Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly
effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic
properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have
infrequently been reported thus far. In the present study, C57BL/6 mice were fed
with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as
a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY
significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and
triglyceride deposition induced by chronic alcohol exposure. In addition, DMY
dramatically attenuated the alcohol-triggered elevation of the level of
inflammatory cytokines and partially recovered hepatic pathological changes.
Notably, DMY remarkably modified aberrant expression of CYP2E1, Keap-1 and HO-1
in the liver and simultaneously ameliorated disordered nuclear localization of NF
kappaB and Nrf2 to exert its hepatoprotective effects. Further mechanistic
exploration suggested that DMY activated Nrf2, possibly mediated through the
autophagy pathway. Analysis of the crosstalk among p62, Keap-1 and Nrf2
demonstrated that the p62 upregulation caused by DMY contributes to a positive
feedback loop in Nrf2 activation. In summary, DMY likely modulates p62 and
autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and
the inflammatory response in the pathological progression of ALD.
PMID- 28419833
TI - Sexual selection, sexual isolation and pheromones in Drosophila melanogaster
strains after long-term maintaining on different diets.
AB - Evolution of reproductive isolation may be a consequence of a variety of signals
used in courtship and mate preferences. Pheromones play an important role in both
sexual selection and sexual isolation. The abundance of pheromones in Drosophila
melanogaster may depend on different environmental factors, including diet. The
aim of this study was to ascertain to which degree principal pheromones affect
sexual selection in D. melanogaster. We used D. melanogaster strains reared for
14 years on four substrates: standard cornmeal substrate and those containing
tomato, banana and carrot. We have previously determined that long-term
maintaining of these dietary strains resulted in differences in their cuticular
hydrocarbons profile (CHs). In this work, we have tested the level of sexual
selection and sexual isolation between aforementioned strains. We found that the
high levels of cis-vaccenyl acetate, 7-pentacosene and 7,11-nonacosadiene in the
strain reared on a substrate containing carrot affected the individual
attractiveness and influenced sexual isolation between flies of this strain and
flies reared on a substrate containing banana. Based on these results, long-term
different diets, may contribute, to sexual behaviour of D. melanogaster via the
effects of principal pheromones.
PMID- 28419834
TI - Sex differences in autonomic response and situational appraisal of a competitive
situation in young adults.
AB - Competition is a social stressor capable of eliciting physiological responses
modulated by the outcome. The main objective of this study was to analyze the
psychophysiological changes associated with competition and its outcome in men
and women, taking into account the role of situational appraisal. To this end,
112 young people (46 men and 66 women) participated in a laboratory task in a
competitive or non-competitive condition, while Blood Pressure (BP), Heart Rate
Variability (HRV), and Skin Conductance (SC) responses were measured. Our results
indicate that competition elicits higher systolic blood pressure (SBP) than a non
competitive task; in addition, winners presented a greater R-R decrease from
baseline to task, greater R-R Recovery, and lower frustration and external
attribution than losers. Regarding sex, men perceived their opponent's capacity
to be lower and their own capacity to be greater than women did, and they also
showed higher R-R decreases and lower SC increases. In conclusion, we found a
complex pattern of different psychophysiological responses to competition
associated with outcome and sex in a laboratory competition. This result could be
related to the use of more passive or active coping strategies.
PMID- 28419835
TI - The architecture and function of the chromatin replication machinery.
AB - Genomic DNA in eukaryotic cells is packaged into nucleosome arrays. During
replication, nucleosomes need to be dismantled ahead of the advancing replication
fork and reassembled on duplicated DNA. The architecture and function of the core
replisome machinery is now beginning to be elucidated, with recent insights
shaping our view on DNA replication processes. Simultaneously, breakthroughs in
our mechanistic understanding of epigenetic inheritance allow us to build new
models of how histone chaperones integrate with the replisome to reshuffle
nucleosomes. The emerging picture indicates that the core eukaryotic DNA
replication machinery has evolved elements that handle nucleosomes to facilitate
chromatin duplication.
PMID- 28419836
TI - Enzymatic behavior of laccase following interaction with gamma-CD and
immobilization into PCL nanofibers.
AB - This study examines the effects of CD use on enzymatic activity, following enzyme
immobilization into nanofibers. There is almost no research available on the
change in enzyme activity following interaction with cyclodextrin and electrospun
nanofiber mats together. Laccase enzyme was immobilized into nanofibrous
structures by various techniques, with and without gamma-CD addition, and the
enzymatic activity of the laccase was analyzed. SEM, XRD, and FTIR analyses were
used for the characterization of the resulting structures. Our results showed
that cyclodextrin use has a positive effect on the enzyme's activity, and
increases its stability. The enzymes treated by cyclodextrin showed activation
after complex formation trials, and no activation loss or enzyme denaturation was
detected. Our conclusions were supported by the enzyme activity test results,
which also showed that immobilization by encapsulation methods gave better
activity results than layering methods. Another important finding concerned the
laccase's stable characteristics that helped to maintain its enzyme activation
after the freeze drying process. Among all test groups, the best activity result
was recorded by laccase-gamma-CD complex encapsulated PCL nanofibers with 96.48
U/mg.
PMID- 28419837
TI - Identification and molecular cloning of novel transcripts of the human kallikrein
related peptidase 10 (KLK10) gene using next-generation sequencing.
AB - Tissue kallikrein and kallikrein-related peptidases (KLKs) form the largest group
of serine proteases in the human genome, sharing many structural and functional
characteristics. Multiple alternative transcripts have been reported for the most
human KLK genes, while many of them are aberrantly expressed in various
malignancies, thus possessing significant prognostic and/or diagnostic value.
Alternative splicing of cancer-related genes is a common cellular mechanism
accounting for cancer cell transcriptome complexity, as it affects cell cycle
control, proliferation, apoptosis, invasion, and metastasis. In this study, we
describe the identification and molecular cloning of eight novel transcripts of
the human KLK10 gene using 3' rapid amplification of cDNA ends (3' RACE) and next
generation sequencing (NGS), as well as their expression analysis in a wide panel
of cell lines, originating from several distinct cancerous and normal tissues.
Bioinformatic analysis revealed that the novel KLK10 transcripts contain new
alternative splicing events between already annotated exons as well as novel
exons. In addition, investigation of their expression profile in a wide panel of
cell lines was performed with nested RT-PCR using variant-specific pairs of
primers. Since many KLK mRNA transcripts possess clinical value, these newly
discovered alternatively spliced KLK10 transcripts appear as new potential
biomarkers for diagnostic and/or prognostic purposes or as targets for
therapeutic strategies.
PMID- 28419838
TI - Peptidoglycan accelerates granulopoiesis through a TLR2- and MyD88-dependent
pathway.
AB - Granulopoiesis is accelerated during Gram-negative bacterial infection through
activation of toll-like receptor 4 (TLR4). In this study, we tested whether
activation of TLR2 promotes granulopoiesis by using the well-known TLR2 agonist,
peptidoglycan (PGN). Neutrophils in bone marrow and spleen, and plasma
granulocyte colony-stimulating factor (G-CSF) were increased in mice that had
received intraperitoneal PGN administration. Incorporation of BrdU into bone
marrow neutrophils increased, demonstrating that PGN accelerated granulopoiesis.
Treatment of bone marrow cells (BMCs) with PGN increased neutrophils in vitro and
promoted the secretion of G-CSF from Ly-6G-Ly-6C+ monocytes. The accelerated
granulopoiesis caused by PGN was not seen in TLR2-deficient and MyD88-deficient
BMCs. Additionally, PGN induced G-CSF production in human umbilical vein
endothelial cells. These findings demonstrate that PGN promotes the secretion of
G-CSF from monocytes and endothelial cells, leading to the acceleration of
granulopoiesis. Our results illustrate that bacterial recognition by TLR2
facilitates granulopoiesis during Gram-positive bacterial infection.
PMID- 28419839
TI - Near-infrared laser irradiation improves the development of mouse pre
implantation embryos.
AB - The aim of the present study was to assess the effects of near-infrared laser
irradiation on the in vitro development of mouse embryos. Female ICR mice were
superovulated with pregnant mare serum gonadotropin and human chorionic
gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were
collected 40 h after administering hCG and cultured in M16 medium. Two-cell
embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula
(approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were
irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse
monitoring system and the timing of blastocyst hatching was evaluated. Some of
the irradiated blastocysts were transferred to the uterine horns of
pseudopregnant recipients immediately after irradiation. Pregnancy rates, and
offspring growth and fertility, were evaluated. Near-infrared laser irradiation
increased the speed of in vitro mouse embryo development. In irradiated
blastocysts, hatching was faster than in control (non-irradiated) blastocysts
(18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to
18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups
were born alive. When 182 control blastocysts were transferred to 17
pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking
pups were born alive. The growth trajectories (up to 5 weeks) of offspring from
irradiated blastocysts were similar to those from control blastocysts. Second
generation offspring from transplanted animals were all fertile. These results
indicate that near-infrared laser irradiation improves the quality of mouse
embryo development in vitro, and increases the live birth rate without affecting
the normality of the offspring. Thus, the near-infrared laser method may enhance
the quality of embryos and contribute to improvements in reproductive
technologies in mammals.
PMID- 28419840
TI - Potent osteogenic activity of a novel imidazobenzimidazole derivative, IBIP.
AB - Bone mass is controlled by a balance between bone resorption and formation by
osteoclasts and osteoblasts, respectively. An imbalance between osteoblasts and
osteoclasts increases the risk of osteoporosis and fractures. Although inhibition
of osteoclasts is beneficial for preventing and treating osteoporosis, enhanced
bone formation through activation of osteoblast differentiation can be a more
promising therapeutic approach. In this study, we attempted to isolate small
molecules that promote osteoblast differentiation and found that IBIP (3-(2,3
dimethoxyphenyl)-1-[9-methyl-2-phenyl-9H-imidazo[1,2-a]benzimidazol-3-yl]-2
propen-1-one) was a potent activator of osteoblast differentiation. Upon bone
morphogenetic protein-2 (BMP2) stimulation, IBIP promoted osteoblast
differentiation and increased the expression of osteoblast-specific gene markers,
such as osterix and alkaline phosphatase, in a dose-dependent manner. The
phosphorylation of SMADs and extracellular signal-regulated kinase (ERK)
increased after IBIP treatment. While enhanced SMAD phosphorylation by IBIP was
abolished by a BMP inhibitor, IBIP-induced ERK phosphorylation was sustained in
the presence of this inhibitor, but was decreased by an ERK kinase inhibitor.
Suppression of IBIP-induced SMAD and ERK phosphorylation diminished osteoblast
differentiation. Most importantly, IBIP enhanced bone formation and calcification
in a BMP2-independent manner in vitro and advanced the skeletal development of
zebrafish larvae in vivo. Collectively, IBIP may have beneficial effects on bone
loss through potentiation of bone formation.
PMID- 28419842
TI - Erratum.
PMID- 28419841
TI - Buffered 1% Lidocaine With Epinephrine Can Be as Effective as Nonbuffered 2%
Lidocaine With Epinephrine for Maxillary Field Block.
AB - PURPOSE: Buffering local anesthetics with epinephrine (Epi) offers clinicians
options not often considered. This study assessed outcomes for pulpal anesthesia,
pain on injection, and time to midface numbness for buffered 1% lidocaine with
1:100,000 Epi versus nonbuffered 2% lidocaine with 1:100,000 Epi. MATERIALS AND
METHODS: In this trial with a randomized, crossover design, buffered 1% lidocaine
was compared with nonbuffered 2% lidocaine. Subjects were adult volunteers who
served as their own controls. The predictor variables were alternate drug
formulations. The outcome variables were subjects' responses to cold and electric
pulp testing (EPT) stimulation of the maxillary first molar and canine, pain
levels during the injection, and time to midface numbness. After maxillary field
blocks with 40 mg of buffered lidocaine or 80 mg of nonbuffered lidocaine,
subjects reported pain on injection and responses of the maxillary first molar
and canine after cold and EPT stimulation. Teeth were tested before field block
and at 30-minute intervals until a positive response was detected. Two weeks
later, subjects were tested with the alternate drug combinations. For all outcome
variables, assessment of treatment difference, calculated as 1% buffered minus 2%
nonbuffered, was performed with the Wilcoxon rank sum test with significance at P
< .05. RESULTS: More of the 24 subjects were women and Caucasian. The median age
was 23.5 years (interquartile range, 21, 25 years), and the median body weight
was 155 lb (interquartile range, 128.5, 176.5 lb). Pain levels during the
injection were significantly lower for 1% buffered lidocaine, with P = .04. Times
to response after injection were not significantly different between the 2 drug
formulations for the cold test on a molar, with P = .08, or the cold test on a
canine, with P = .22. However, times to response were significantly longer for
nonbuffered drugs for EPT on the molar and canine, both with P = .01.
CONCLUSIONS: Buffering 1% lidocaine with 1:100,000 Epi reduces the pain on
injection with a maxillary field block and results in similar lengths of pulpal
anesthesia tested with a cold stimulus as compared with nonbuffered 2% lidocaine
with 1:100,000 Epi.
PMID- 28419843
TI - A Review of In-Office Dynamic Image Navigation for Extraction of Complex
Mandibular Third Molars.
AB - PURPOSE: We performed a retrospective review of in-office removal of complex
mandibular third molars with a dynamic image navigation system (DINS). MATERIALS
AND METHODS: A retrospective review was conducted of cases completed from 2010 to
2014 by a single oral and maxillofacial surgeon. The average age of the patients
was 47 years (range, 27 to 72 years). Extraction complexity was classified with
Juodzbalys and Daugela's classification system. The included study cases had
complexity scores of 9 or greater. Each patient received custom intraoral splints
to secure the tracking array and underwent cone beam computed tomography image
acquisition. All surgical procedures were performed with a precalibrated tracking
straight handpiece under dynamic navigation. RESULTS: All 25 cases were treated
successfully with the use of the DINS. Twelve of these cases were associated with
pathologic lesions. Three patients were noted to have inferior alveolar nerve
paresthesia. One patient sustained a pathologic fracture at week 2. Postoperative
infections were noted in 7 cases, 2 of which had a pre-existing infection. One
patient reported temporary limitation of mouth opening. A coronectomy was
performed in 1 case. CONCLUSIONS: We present results using a new technology, the
DINS, for removal of complex mandibular third molars. Potential advantages are 1)
improved visualization and localization of anatomic structures such as the
inferior alveolar nerve, lingual cortical plate, and adjacent roots; 2) improved
control during osteotomy; 3) decreased surgical access requirements and reduction
in overall bone removal; 4) ability to perform complex procedures successfully in
an in-office setting; 5) decreased surgical time resulting from improved
visualization; and 6) potential use as a teaching tool. Possible limitations of
the use of an in-office DINS include increased cost, increased time attributed to
presurgical planning, initial learning curve, and optical array interference by
the surgeon or assistants during surgery.
PMID- 28419844
TI - Triple-Cut Computer-Aided Design-Computer-Aided Modeling: More Oncologic Safety
Added to Precise Mandible Modeling.
AB - PURPOSE: Computer-aided design-computer-aided modeling (CAD-CAM) has become
standard in mandibular reconstruction because it offers better outcomes.
Occasionally, the reconstructive plans need to be changed intraoperatively and
the custom-made prefabricated devices may become inadequate. We present an
efficient adjunct to the standard CAD-CAM technique that resolves this problem.
MATERIALS AND METHODS: Customized surgical devices with our "triple-cut" concept
were used in 5 patients for mandibular reconstruction with free fibula flap (4
after mandibular resection for squamous cell carcinoma and 1 after mandibular
osteoradionecrosis). In all patients the mandibular and fibular cutting guides
were provided with 3 different cutting levels per side. RESULTS: Three different
cutting levels on the mandible permitted an accurate resection based on the
intraoperative needs. The corresponding 3 "cutting levels" on the fibula created
perfectly matching segments of vascularized bone. Good contact of bony segments
was obtained in all patients. CONCLUSIONS: The prefabricated triple-cut cutting
guides make changing the dimensions of bony resection, while still using the
prefabricated CAD-CAM reconstructive plate, possible.
PMID- 28419845
TI - Does Orthognathic Surgery Cause or Cure Temporomandibular Disorders? A Systematic
Review and Meta-Analysis.
AB - PURPOSE: There is still controversy about whether orthognathic surgery negatively
or positively affects temporomandibular disorders (TMDs). The purpose of this
study was to determine whether orthognathic surgery has a beneficial or
deleterious effect on pre-existing TMDs. MATERIALS AND METHODS: A systematic
review and meta-analysis were conducted based on Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched 3 major
databases to locate all pertinent articles published from 1980 to March 2016. All
subjects in the various studies were stratified a priori into 9 categories based
on subdiagnoses of TMDs. The predictor variables were those patients with pre
existing TMDs who underwent orthognathic surgery in various subgroups. The
outcome variables were maximal mouth opening and signs and symptoms of a TMD
before and after orthognathic surgery based on the type of osteotomy. The meta
analysis was performed using Comprehensive Meta-Analysis software (Biostat,
Englewood, NJ). RESULTS: A total of 5,029 patients enrolled in 29 studies were
included in this meta-analysis. There was a significant reduction in TMDs in
patients with a retrognathic mandible after bilateral sagittal split osteotomy
(BSSO) (P = .014), but no significant difference after bimaxillary surgery (BSSO
and Le Fort I osteotomy) (P = .336). There was a significant difference in
patients with prognathism after isolated BSSO or intraoral vertical ramus
osteotomy and after combined BSSO and Le Fort I osteotomy (P = .001), but no
significant difference after BSSO (P = .424) or bimaxillary surgery (intraoral
vertical ramus osteotomy and Le Fort I osteotomy) (P = .728). CONCLUSIONS:
Orthognathic surgery caused a decrease in TMD symptoms for many patients who had
symptoms before surgery, but it created symptoms in a smaller group of patients
who were asymptomatic before surgery. The presence of presurgical TMD symptoms or
the type of jaw deformity did not identify which patients' TMDs would improve,
remain the same, or worsen after surgery.
PMID- 28419846
TI - Bit1 Regulates Cell Migration and Survival in Oral Squamous Cell Carcinoma.
AB - PURPOSE: Increasing evidence has shown that Bcl-2 inhibitor of transcription 1
(Bit1) involves a variety of biological processes in the process of tumor
development and progression. We hypothesized that Bit1 would be overexpressed in
oral squamous cell carcinoma (OSCC); therefore, we examined Bit1 gene expression
and protein production, as well as explored the effect of elevated Bit1 levels on
OSCC cells. MATERIALS AND METHODS: We investigated the use of quantitative real
time reverse transcription-polymerase chain reaction and immunohistochemistry
analysis for Bit1 messenger RNA and protein levels. We used 75 OSCC specimens, 25
tumor-adjacent dysplasia specimens, and 25 normal oral tissue samples that
matched OSCC specimens in this study. We also transfected Bit1 complementary DNA
into human oral cancer cells (Tca8113) to further investigate the potential role
of Bit1 in OSCC. RESULTS: We found that Bit1 levels in OSCC tissues were
significantly higher than those in tumor-adjacent dysplasia specimens and normal
oral tissue (P < .05). We also confirmed that Bit1 overexpression in the cytosol
of Tca8113 cells induced apoptosis. CONCLUSIONS: Our findings suggest Bit1
overexpression may contribute to oral cancer cell survival and dissemination. In
the future, Bit1 may be an important diagnostic and therapeutic target.
PMID- 28419847
TI - The Oral and Maxillofacial Surgery Anesthesia Team Model.
AB - Oral and maxillofacial surgeons have been providing safe anesthesia to their
patients using the anesthesia team model; this has allowed access to care for
patients that have significant anxiety. The AAOMS strives to maintain the
excellent safety record of the anesthesia team model by creating simulation
programs in anesthesia, regularly updating the office anesthesia evaluation
program, convening anesthesia safety conferences and strengthening the standards
in our training programs. Through these efforts, our delivery of anesthesia to
our patients will remain safe and effective.
PMID- 28419848
TI - Toll-like receptor activation, vascular endothelial function, and hypertensive
disorders of pregnancy.
AB - Aberrant innate immune system activation in the mother contributes greatly to the
development of hypertension during pregnancy. Numerous groups have elicited
vascular inflammation, endothelial dysfunction, and hypertension in animals
during gestation by directly activating Toll-like receptors. Additionally,
several experimental therapies that reduce pro-inflammatory immune cells and
cytokines restore vascular endothelial function and normalize blood pressure.
This review will summarize the research demonstrating that an excessive maternal
innate immune response is sufficient to cause vascular inflammation and
endothelial dysfunction, which contributes to the development of hypertension
during pregnancy. Dampening the vascular inflammation caused by immune responses
may reduce the incidence and severity of hypertensive disorders of pregnancy.
PMID- 28419849
TI - RIFM fragrance ingredient safety assessment, isoamyl formate, CAS Registry Number
110-45-2.
PMID- 28419851
TI - An emergent functional parcellation of the temporal cortex.
AB - The temporal lobe has been associated with various cognitive functions which
include memory, auditory cognition and semantics. However, at a higher level of
conceptualisation, all of the functions associated with the temporal lobe can be
considered as lying along one major axis; from modality-specific to modality
general processing. This paper used a spectral reordering technique on resting
state and task-based functional data to extract the major organisational axis of
the temporal lobe in a bottom-up, data-driven fashion. Independent parcellations
were performed on resting-state scans from 71 participants and active semantic
task scans from 23 participants acquired using dual echo gradient echo planar
imaging in order to preserve signal in inferior temporal cortex. The resulting
organisational axis was consistent (over dataset and hemisphere) and progressed
from superior temporal gyrus and posterior inferior temporal cortex to
ventrolateral anterior temporal cortex. A hard parcellation separated a posterior
(superior temporal and posterior fusiform and inferior temporal gyri) and an
anterior cluster (ventrolateral anterior temporal lobe). The functional
connectivity of the hard clusters supported the hypothesis that the connectivity
gradient separated modality-specific and modality-general regions. This
hypothesis was then directly tested by performing a VOI analysis upon an
independent semantic task-based data set including auditory and visually
presented stimuli. This confirmed that the ventrolateral anterior aspects of the
temporal lobe are associated with modality-general processes whilst posterior and
superior aspects are specific to certain modalities, with the posterior inferior
subregions involved in visual processes and superior regions involved in
audition.
PMID- 28419850
TI - Overpressure blast injury-induced oxidative stress and neuroinflammation response
in rat frontal cortex and cerebellum.
AB - BACKGROUND & AIM: Overpressure blast-wave induced brain injury (OBI) and its long
term neurological outcome pose significant concerns for military personnel. Our
aim is to investigate the mechanism of injury due to OBI. METHODS: Rats were
divided into 3 groups: (1) Control, (2) OBI (exposed 30psi peak pressure, 2
2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and
brain (cortex and cerebellum) tissues were collected at 24h post injury. RESULTS:
The neurological examination score was worse in OBI and r-OBI (4.2+/-0.6 and
3.7+/-0.5, respectively) versus controls (0.7+/-0.2). A significant positive
correlation between lung and brain edema was found. Malondialdehyde (index for
lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex
(p<0.05) and cerebellum (p<0.01-0.001). The glutathione (endogenous antioxidant)
level decreased in cortex (p<0.01) and cerebellum (p<0.05) of r-OBI group when
compared with the controls. Myeloperoxidase activity indicating neutrophil
infiltration, was significantly (p<0.01-0.05) elevated in r-OBI. Additionally,
tissue thromboplastin activity, a coagulation marker, was elevated, indicating a
tendency to bleed. NGF and NF-kappaB proteins along with Iba-1 and GFAP
immunoreactivity significantly augmented in the frontal cortex demonstrating
microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin,
were also elevated. CONCLUSION: OBI triggers both inflammation and oxidative
injury in the brain. This data in conjunction with our previous observations
suggests that OBI triggers a cascade of events beginning with impaired cerebral
vascular function leading to ischemia and chronic neurological consequences.
PMID- 28419852
TI - Reliability of volumetric and surface-based normalisation and smoothing
techniques for PET analysis of the cortex: A test-retest analysis using [11C]SCH
23390.
AB - Parametric voxelwise analysis is a commonly used tool in neuroimaging, as it
allows for identification of regions of effects in the absence of a strong a
priori regional hypothesis by comparing each voxel of the brain independently.
Due to the inherent imprecision of single voxel measurements, spatial smoothing
is performed to increase the signal-to-noise ratio of single-voxel estimates. In
addition, smoothing compensates for imprecisions in anatomical registration, and
allows for the use of cluster-based statistical thresholding. Smoothing has
traditionally been applied in three dimensions, without taking the tissue types
of surrounding voxels into account. This procedure may be suitable for
subcortical structures, but is problematic for cortical regions for which grey
matter often constitutes only a small proportion of the smoothed signal. New
methods have been developed for cortical analysis in which voxels are sampled to
a surface, and smoothing is restricted to neighbouring regions along the cortical
grey matter in two dimensions. This procedure has recently been shown to decrease
intersubject variability and bias of PET data. The aim of this study was to
compare the variability, bias and test-retest reliability of volumetric and
surface-based methods as they are applied in practice. Fifteen healthy young
males were each measured twice using the dopamine D1 receptor radioligand
[11C]SCH-23390, and analyses were performed at the level of individual voxels and
vertices within the cortex. We found that surface-based methods yielded higher
BPND values, lower coefficient of variation, less bias, better reliability and
more precise estimates of parametric binding. All in all, these results suggest
that surface-based methods exhibit superior performance to volumetric approaches
for voxelwise analysis of PET data, and we advocate for their use when a ROI
based analysis is not appropriate.
PMID- 28419853
TI - Listeria monocytogenes meningitis in the Netherlands, 1985-2014: A nationwide
surveillance study.
AB - OBJECTIVES: Listeria monocytogenes can cause sepsis and meningitis. We report
national surveillance data on L. monocytogenes meningitis in the Netherlands,
describing incidence changes, genetic epidemiology and fatality rate. METHODS: We
analyzed data from the Netherlands Reference Laboratory of Bacterial Meningitis
for cases of L. monocytogenes meningitis. Strains were assessed by serotyping and
bacterial population structure by multi-locus sequence typing. RESULTS: A total
of 375 cases of Listeria meningitis were identified between 1985 and 2014. Peak
incidence rates were observed in neonates (0.61 per 100,000 live births) and
older adults (peak at 87 year; 0.53 cases per 100,000 population of the same
age). Neonatal listerial meningitis decreased 17-fold from 1.95 per 100,000 live
births between 1985 and 1989, to 0.11 per 100,000 live births between 2010 and
2014. Overall case fatality rate was 31%, in a multivariate analysis older age
and concomitant bacteremia were associated with mortality (both p < 0.01). Clonal
complexes (CC) CC1, CC2 and CC3 decreased over time from respectively 32% to 12%,
33% to 9% and 10% to 2% (all p < 0.001), while CC6 increased from 2% to 26% (p <
0.001). CONCLUSIONS: The incidence of neonatal listerial meningitis has declined
over the past 25 years. The genotype CC6 has become the predominant genotype in
listerial meningitis in the Netherlands. Mortality of listeria meningitis has
remained high.
PMID- 28419854
TI - A formalin-inactivated vaccine provides good protection against Vibrio harveyi
infection in orange-spotted grouper (Epinephelus coioides).
AB - Vibrio harveyi is one of the most common threats to farmed grouper, so
considerable efforts are in practice to control the pathogen. This study presents
a highly effective vaccine against V. harveyi in the orange-spotted grouper with
the help of a single intraperitoneal immunization. The vaccine candidate was in
form of whole, formalin-inactivated V. harveyi cells combined with a
metabolizable ISA763 AVG adjuvant. Our results indicated that the vaccine
triggered a remarkably higher expression level of interleukin (IL)-1beta, IL-6,
IL-8, and IL-10 in the groupers' kidneys and spleens, as recorded after 1 and 3
days of immunization. Antibody titers were significantly elevated in the
vaccinated fish. A pivotal observation was that the vaccine highly protected the
grouper from a homologous V. harveyi strain challenge with relative percentage
survival values of 100% and 91.7% at 6 and 12 weeks post-immunization,
respectively. Vaccinated fish also demonstrated strong cross-protection against a
heterologous bacterial isolate challenge. Therefore, the inactivated V. harveyi
vaccine is a promising candidate that could stimulate good immune responses and
confer remarkable protection in farmed groupers.
PMID- 28419856
TI - Adenoma Prevalence in Blacks and Whites Having Equal Adherence To Screening
Colonoscopy: The National Colonoscopy Study.
PMID- 28419855
TI - A Randomized Trial of Silymarin for the Treatment of Nonalcoholic
Steatohepatitis.
AB - BACKGROUND & AIMS: Silymarin is a complex mixture of 6 major flavonolignans and
other minor polyphenolic compounds derived from the milk thistle plant Silybum
marianum; it has shown antioxidant, anti-inflammatory and antifibrotic effects,
and may be useful in patients with nonalcoholic fatty liver disease (NAFLD). We
aimed to study the efficacy of silymarin in patients with nonalcoholic
steatohepatitis (NASH)-the more severe form of NAFLD. METHODS: We performed a
randomized, double-blind, placebo-controlled trial of consecutive adults with
biopsy-proven NASH and a NAFLD activity score (NAS) of 4 or more at a tertiary
care hospital in Kuala Lumpur, Malaysia, from November 2012 through August 2014.
Patients were randomly assigned to groups given silymarin (700 mg; n = 49
patients) or placebo (n = 50 patients) 3 times daily for 48 weeks. After this 48
week period, liver biopsies were repeated. The primary efficacy outcome was a
decrease of 30% or more in NAS; findings from 48-week liver biopsies were
compared with those from the baseline biopsy. Secondary outcomes included changes
in steatosis, lobular inflammation, hepatocyte ballooning, NAS and fibrosis
score, and anthropometric measurements, as well as glycemic, lipid, and liver
profiles and liver stiffness measurements. RESULTS: The percentage of patients
achieving the primary efficacy outcome did not differ significantly between the
groups (32.7% in the silymarin group vs 26.0% in the placebo group; P = .467). A
significantly higher proportion of patients in the silymarin group had reductions
in fibrosis based on histology (reductions of 1 point or more; 22.4%) than did
the placebo group (6.0%; P = .023), and based on liver stiffness measurements
(decrease of 30% or more; 24.2%) than did the placebo group (2.3%; P = .002). The
silymarin group also had significant reductions in mean aspartate
aminotransferase to platelet ratio index (reduction of 0.14, P = .011 compared
with baseline), fibrosis-4 score (reduction of 0.20, P = .041 compared with
baseline), and NAFLD fibrosis score (reduction of 0.30, P < .001 compared with
baseline); these changes were not observed in the placebo group (reduction of
0.07, P = .154; increase of 0.18, P = .389; and reduction of 0.05, P = .845,
respectively). There was no significant difference between groups in number of
adverse events; adverse events that occurred were not attributed to silymarin.
CONCLUSIONS: In a randomized trial of 99 patients, we found that silymarin (700
mg, given 3 times daily for 48 weeks) did not reduce NAS scores by 30% or more in
a significantly larger proportion of patients with NASH than placebo. Silymarin
may reduce liver fibrosis but this remains to be confirmed in a larger trial. It
appears to be safe and well tolerated. ClinicalTrials.gov: NCT02006498.
PMID- 28419857
TI - Making a Great Journal Even Better.
PMID- 28419858
TI - Reply.
PMID- 28419859
TI - Endoscopic Ultrasound Liver Biopsies Accurately Predict the Presence of Fibrosis
in Patients With Fatty liver.
PMID- 28419860
TI - Pedunculated Laryngeal Hemangioma in a Patient With Suspected Atypical Symptoms
of GERD.
PMID- 28419861
TI - Agroecological and environmental factors influence Barley yellow dwarf viruses in
grasslands in the US Pacific Northwest.
AB - Plant pathogens can play a role in the competitive interactions between plant
species and have been understudied in native prairies, which are declining
globally, and in Conservation Reserve Program (CRP) lands in the United States.
Barley/Cereal yellow dwarf virus (B/CYDV) are among the most economically
important disease-causing agents of small grain cereal crops, such as wheat, and
are known to infect over 150 Poaceae species, including many of the grass species
present in prairies and CRP lands. Field surveys of Poaceae species were
conducted in endangered Palouse Prairie and CRP habitats of southeastern
Washington and adjacent northern Idaho, USA from 2010 to 2012 to examine for the
presence of B/CYDV among plant hosts and aphid vectors. Viral species were
identified via cloning and sequencing. Landscape, soil and climate data were
retrieved from USDA-NASS and USDA-NRCS databases. Analyses were conducted to
examine effects of diverse agroecological and environmental factors on virus
prevalence. A total of 2271 grass samples representing 30 species were collected;
28 of these were infected with BYDV in at least one location. BYDV infection was
detected at every CRP and prairie remnant sampled, with an overall infection of
46%. BYDV-SGV and BYDV-PAV were the only two B/CYDV species encountered, with
BYDV-SGV being more prevalent. Sampling time (season) and host plant identity
were the main variables explaining variation in virus prevalence among sites.
BYDV was more prevalent in perennial compared to annual grass species. Aphids
were encountered only once suggesting non-colonizing aphids, potentially from
neighboring cereal fields, are responsible for disease spread in these habitats.
BYDV prevalence increased in sampled habitats as cereal crop cover increased
within a 1-km radius of a habitat patch. Results demonstrate moderate to high and
persistent prevalence of BYDV in an endangered grassland habitat. Species
composition and susceptibility to pathogens should be considered when creating
seed mixes for CRP sites, especially in relation to agricultural crops and
diseases in a region. Future work exploring host abundance, competence and
habitat utilization by vectors is required to fully elucidate BYDV ecology and
epidemiology in grassland habitats.
PMID- 28419862
TI - The effect of tDCS over the right temporo-parietal junction on pain empathy.
AB - Empathy is a complex psychological phenomenon crucial for social perception and
interactions. Several lines of evidence suggest that the right temporo-parietal
junction is involved in self-other control mechanisms that play an important role
in empathic responses. However, limited direct evidence of the involvement of
this region in empathic responses is currently available. In this study,
inhibitory transcranial direct current stimulation over this region influenced
empathic responses to others' pain. It was found that compared to participants
that received anodal or sham transcranial direct current stimulation,
participants who received cathodal transcranial direct current stimulation over
the right temporo-parietal junction perceived the pain of others as less intense
compared to sham stimulation and showed decreased late event related potentials
to facial expressions of pain. Furthermore, it was found the stimulation had no
significant effect on measures of sensorimotor resonance and physiological
responses to pain in others. Our results demonstrate that the right temporo
parietal junction plays a role in empathic responses and that its inhibition can
decrease behavioural and cerebral measures related to the cognitive-evaluative
component of empathy. It is proposed that the right temporo-parietal junction is
a valid stimulation target to study the influence of self-other control in
empathic processes and could be useful to study the involvement of this region
observed in clinical conditions characterized by altered empathic responses.
PMID- 28419863
TI - Cellular stress response in human Muller cells (MIO-M1) after bevacizumab
treatment.
AB - Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely
used in the treatment of retinal vascular diseases. However, due to the essential
role Muller cell derived-VEGF plays in the maintenance of retinal neurons and
glial cells, cell viability is likely to be affected by VEGF inhibition. We
therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Muller
cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media
containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium
only. Cell viability was determined with the trypan blue exclusion test and MTT
assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin
content were quantified by immunohistochemistry. Gene expression was evaluated by
real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell
viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced
apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25
and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3
mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with
bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with
structural protein abnormalities, with decreased GFAP and vimentin content and
upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not
significantly affect MIO-M1 cell viability, it led to metabolic and molecular
changes (apoptosis, autophagy and structural abnormalities) suggestive of
significant cellular toxicity.
PMID- 28419864
TI - How to be a good neighbour: Facilitation and competition between two co-flowering
species.
AB - Empirical evidence suggests that co-flowering species can facilitate each other
through shared pollinators. However, the extent to which one co-flowering species
can relieve pollination limitation of another while simultaneously competing for
abiotic resource has rarely been examined. Using a deterministic model we
explored the demographic outcome for one ("focal") species of its co-occurrence
with a species that shares pollinators and competes for both pollinator
visitation and abiotic resources. In this paper we showed how the overall impact
can be positive or negative, depending on the balance between enhanced
fertilization versus increased competition. Our model could predict the density
of co-flowering species that will maximize the pollination rate of the focal
species by attracting pollinators. Because that density will also give rise to
competitive effects, a lower density of co-flowering species is required for
optimizing the trade-off between enhanced fertilization and competition so as to
give the maximum possible facilitation of reproduction in the focal species.
Results were qualitatively different when we considered attractiveness of the co
flowering species, as opposed to its density, because attractiveness, unlike
density, had no effect on competition for abiotic resources. Whereas unattractive
neighbours would not bring in pollinators, very attractive neighbours would
captivate pollinators, not sharing them with the focal species. Thus optimal
benefit to the focal species came at intermediate levels of attractiveness in the
co-flowering species. This intermediate level of attractiveness in co-flowering
species simultaneously maximized pollination and overall facilitation of
reproduction for the focal species. The likelihood of facilitation was predicted
to decline with the selfing rate of the focal species, revealing an indirect cost
for an inbreeding mating system. Whether a co-flowering species can be
facilitative depends on the way pollinators respond to the plant density: only a
Type III functional response for visitation rate can result in facilitation. Our
model provided both a conceptual framework and precise quantitative measures for
determining the impacts of a neighbouring co-flowering species on reproduction.
PMID- 28419865
TI - The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic
arthritis in mice.
AB - Septic arthritis is a severe and rapidly debilitating disease associated with
severe joint pain, inflammation and oxidative stress. Nitroxyl (HNO) has become a
nitrogen oxide of significant interest due to its pharmacological endpoints that
are potentially favorable for treating varied diseases. However, whether HNO also
serves as a treatment to septic arthritis is currently unknown. The aim of this
study was to investigate the effect of the HNO donor, Angeli's salt (AS), in the
outcome of chronic Staphylococcus aureus (S. aureus)-induced septic arthritis in
mice. Daily treatment with AS inhibited mechanical hyperalgesia and inflammation
(edema, leukocyte migration, cytokines release and NF-kappaB activation, and
oxidative stress) resulting in reduced disease severity (clinical course,
histopathological changes, proteoglycan levels in the joints, and
osteoclastogenesis). In addition, AS decreased the number of S. aureus colony
forming unities in synovial tissue, enhanced the bactericidal effect of
macrophages and inhibited the worsening of systemic inflammatory response
(leukocyte counts in the lung and systemic proinflammatory cytokine
concentration). Our results suggest for the first time the therapeutic potential
of AS in a model of septic arthritis by mechanisms involving microbicidal
effects, anti-inflammatory actions and reduction of disease severity.
PMID- 28419866
TI - O-Aminobenzoyl-S-nitrosoglutathione: A fluorogenic, cell permeable, pseudo
substrate for S-nitrosoglutathione reductase.
AB - S-nitrosoglutathione reductase (GSNOR) is a multifunctional enzyme. It can
catalyze NADH-dependent reduction of S-nitrosoglutathione (GSNO); as well as NAD+
dependent oxidation of hydroxymethylglutathione (HMGSH; an adduct formed by the
spontaneous reaction between formaldehyde and glutathione). While initially
recognized as the enzyme that is involved in formaldehyde detoxification,
increasing amount of evidence has shown that GSNOR also plays a significant role
in nitric oxide mediated signaling through its modulation of protein S
nitrosothiol signaling. In humans, GSNOR/S-nitrosothiols have been implicated in
the etiology of several diseases including lung cancer, cystic fibrosis, asthma,
pulmonary hypertension, and neuronal dysfunction. Currently, it is not possible
to monitor the activity of GSNOR in live cells. In this article, we present a new
compound, O-aminobenzoyl-S-nitrosoglutathione (OAbz-GSNO), which acts as a
fluorogenic pseudo-substrate for GSNOR with an estimated Km value of 320uM. The
weak OAbz-GSNO fluorescence increases by approximately 14 fold upon reduction of
its S-NO moiety. In live cell imaging studies, OAbz-GSNO is readily taken up by
primary pulmonary endothelial cells and localizes to the same perinuclear region
as GSNOR. The perinuclear OAbz-GSNO fluorescence increases in a time dependent
manner and this increase in fluorescence is abolished by siRNA knockdown of GSNOR
or by treatment with GSNOR-specific inhibitors N6022 and C3. Taken together,
these data demonstrate that OAbz-GSNO can be used as a tool to monitor the
activity of GSNOR in live cells.
PMID- 28419867
TI - Sustained blockade of ascorbic acid transport associated with marked SVCT1 loss
in rat hepatocytes containing increased ascorbic acid levels after partial
hepatectomy.
AB - The liver has an extraordinary regenerative capacity in response to partial
hepatectomy (PHx), which develops with neither tissue inflammation response nor
alterations in the whole organism. This process is highly coordinated and it has
been associated with changes in glutathione (GSH) metabolism. However, there are
no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and
GSH act integrally as an antioxidant system that protects cells and tissues from
oxidative damage and imbalance observed in a variety of diseases that affect the
liver. Although rat hepatocytes are able to synthesize AA and GSH, which are the
providers of AA for the whole organism, they also acquire AA from extracellular
sources through the sodium-coupled ascorbic acid transporter-1 (SVCT1). Here, we
show that hepatocytes from rat livers subjected to PHx increase their GSH and AA
levels from 1 to 7 days post hepatectomy, whose peaks precede the peak in cell
proliferation observed at 3 days post-hepatectomy. The increase in both
antioxidants was associated with higher expression of the enzymes involved in
their synthesis, such as the modifier subunit of enzyme glutamine cysteine ligase
(GCLM), glutathione synthetase (GS), gulonolactonase (GLN) and gulonolactone
oxidase (GULO). Importantly, rat hepatocytes, that normally exhibit kinetic
evidence indicating only SVCT1-mediated transport of AA, lost more than 90% of
their capacity to transport it at day 1 after PHx without evidence of recovery at
day 7. This observation was in agreement with loss of SVCT1 protein expression,
which was undetectable in hepatocytes as early as 2h after PHx, with partial
recovery at day 7, when the regenerated liver weight returns to normal. We
conclude that after PHx, rat hepatocytes enhance their antioxidant capacity by
increasing GSH and AA levels prior to the proliferative peak. GSH and AA are
increased by de novo synthesis, however paradoxically hepatocytes from rat
subjected to PHx also suppress their capacity to acquire AA from extracellular
sources through SVCT1.
PMID- 28419868
TI - Ciprofloxacin resistance in uropathogenic Escherichia coli isolates causing
community-acquired urinary infections in Brasilia, Brazil.
AB - OBJECTIVES: Considering the global concern of ciprofloxacin resistance, the aim
of this study was to evaluate the characteristics of ciprofloxacin-resistant (CIP
R) Escherichia coli isolated from patients with community-acquired urinary tract
infections (UTIs) in Brasilia, Brazil. METHODS: CIP-R E. coli isolated from
different outpatients between July 2013 and April 2014 in a tertiary hospital
were analysed for antibiotic resistance profile, phylotype, uropathogenic E. coli
(UPEC) virulence genes, clonal relationship by enterobacterial repetitive
intergenic consensus PCR (ERIC-PCR), and multilocus sequence typing (MLST).
RESULTS: Among the 324 UPEC analysed, 263 (81.2%) were ciprofloxacin-sensitive
and 61 (18.8%) were CIP-R. Antibiogram analysis of the 61 CIP-R strains showed
that 45 (73.8%) were also multidrug-resistant. The most prevalent phylogroups
were A and B2 (26/61 and 18/61, respectively). traT (53/61) and aer-traT (24/61)
were the most common gene and genotype observed. Dendrogram analysis found that
multidrug resistance and virulence genes were distributed among CIP-R strains
independently of clonality and phylogroup. Six ERIC clusters (strains sharing
>=85% genetic similarity) were observed. MLST analysis of all strains of each
cluster identified sequence types (STs) associated with worldwide antimicrobial
resistance dissemination, including B2-ST131 and ST410, as well as STs not yet
associated with antimicrobial resistance propagation, such as ST1725 and ST179.
CONCLUSIONS: These results demonstrate that ciprofloxacin resistance
dissemination by UPEC causing community-acquired UTIs was associated with
multidrug resistance and was promoted by pandemic and non-pandemic STs, a
concerning scenario for the local population.
PMID- 28419869
TI - Allodemic distribution of plasmids co-harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB
in Klebsiella pneumoniae is the main source of extended-spectrum beta-lactamases
in Uruguay's paediatric hospital.
AB - OBJECTIVES: This study aimed to describe the characteristics of clinical isolates
of extended-spectrum beta-lactamase (ESBL)-producing enterobacteria (EPE) in
Uruguay's paediatric hospital. METHODS: ESBLs, qnr alleles and aac(6')-Ib-cr were
sought and characterised in EPE isolated between March 2010 and March 2012.
Transfer of resistance determinants was assessed by conjugation. Incompatibility
(Inc) groups, plasmid toxin-antitoxin systems (TAS) and plasmid size were
determined in transconjugants. Clonality was analysed by pulsed-field gel
electrophoresis. Multilocus sequence typing was done for ESBL-producing
Klebsiella pneumoniae. RESULTS: A total of 77 EPE isolates were characterised,
comprising 43% K. pneumoniae, 19.5% Serratia marcescens, 19.5% Escherichia coli,
17% Enterobacter cloacae and 1% Klebsiella oxytoca. ESBLs belonged mainly to the
blaCTX-M family (69.6%) [blaCTX-M-15 (45%) and blaCTX-M-2 (31%)]. The aac(6')-Ib
cr/qnrB duplex was the most frequently detected plasmid-mediated quinolone
resistance mechanism; this association was detected in K. pneumoniae harbouring
blaCTX-M-15. Transconjugants were obtained for 71% of the EPE. Amongst
transconjugants, certain combinations were found between ESBLs and Inc group,
e.g. IncA/C-blaCTX-M-2, IncHI1/HI2-blaCTX-M-9 and IncHI1/HI2-blaSHV-12. In
addition, the combination ccdAB-blaCTX-M-15 was also found. K. pneumoniae
isolates harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB showed allodemic behaviour,
with a predominance of ST14, ST45 and ST48. CONCLUSIONS: In this study,
epidemiological changes in ESBL distribution could be explained by the spread of
K. pneumoniae harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB, encoded mainly on
conjugative plasmids featuring ccdAB TAS. Since reports of TAS in K. pneumoniae
plasmids are scarce, new strategies are needed to combat intrinsic selection
pressure exerted by the association, in conjugative plasmids, of resistance
mechanisms with TAS.
PMID- 28419870
TI - Methicillin-resistant Staphylococcus aureus nasal colonisation amongst healthcare
workers in Kurdistan Region, Iraq.
AB - OBJECTIVES: The aim of this study was to determine the prevalence of nasal
carriage of methicillin-resistant Staphylococcus aureus (MRSA) among healthcare
workers (HCWs) compared with non-HCWs at Duhok city, Kurdistan Region, northern
Iraq. METHODS: A total of 182 HCWs with different occupations and working in
different hospital units as well as 198 non-HCWs were recruited. Nasal swab
samples were collected and were inoculated on mannitol salt agar and incubated at
35 degrees C for 48h. Isolates identified as S. aureus underwent antimicrobial
sensitivity testing to oxacillin. MRSA isolates were selected and investigated
for presence of the mecA gene. RESULTS: Among the HCWs, 41/182 (22.5%) were
carriers of S. aureus compared with 37/198 (18.7%) non-HCWs (P=0.4). Amongst the
S. aureus carriers, 25/41 strains (61.0%) isolated from HCWs were MRSA compared
with 8/37 strains (21.6%) isolated from non-HCWs (P=0.039). The mean age of MRSA
carriers was 35.6+/-6.7years compared with 30+/-5.8years for MRSA non-carriers
(P=0.0177). The mean working years of MRSA carriers was significantly higher than
that of MRSA non-carriers (7.8+/-5.5years vs. 3.9+/-5.3years; P=0.04).
CONCLUSIONS: The prevalence of MRSA was very high amongst HCWs. Regular screening
of carriers is required for prevention of nosocomial infections.
PMID- 28419871
TI - Short-term inhibition of GABAergic IPSCs induced by association of pre- and
postsynaptic activation in the neonatal hippocampus.
AB - Activity-dependent plasticity including short and long-term depression
accompanied by a reduction in transmitter release probability has been
demonstrated in both inhibitory and excitatory synapses. In the neonatal
hippocampus, repetitive postsynaptic depolarization is followed by presynaptic
alterations of the efficacy of GABAAergic transmission. Both facilitation and
inhibition have been observed, but the mechanisms underlying this plasticity have
not yet been elucidated. In the present experiment, repetitive postsynaptic
depolarization by itself did not cause marked alterations of spontaneous
inhibitory postsynaptic currents (sIPSCs). Activation of presynaptic neurons by
increasing extracellular K+ concentration ([K+]o) temporarily induced
facilitation of sIPSCs, but successive repetitive depolarizations transiently
reduced the current frequency. This newly discovered inhibition was expressed
presynaptically, could not be induced by postsynaptic depolarization alone, and
was facilitated by the activation of NMDA receptors. IPSC inhibition was
suppressed using the antagonists of metabotropic glutamate receptors (mGluRs) or
muscarinic ACh receptors (mAChRs). Furthermore, transient inhibition was reduced
by an antagonist of the type 1 cannabinoid receptor (CB1 receptor). The effect of
CB1 receptor agonist on the sIPSCs was potentiated by [K+]o elevation, implying a
role for the [K+]o elevation other than the release of transmitters. These
results show that weak postsynaptic activation, when combined with presynaptic
activation, leads to an inhibition of GABAergic synapses in the neonatal
hippocampus. This inhibition is mediated by a mechanism involving mGluRs, mAChRs,
and CB1 receptors, and potentiated by NMDA receptor activation.
PMID- 28419872
TI - Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction
in female mice from two models of Rett syndrome.
AB - Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by
severe behavioral and physiological symptoms. Mutations in the methyl CpG binding
protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there
is no cure for this devastating disorder. Recently we have demonstrated that
neurobehavioral and brain molecular alterations can be rescued in a RTT mouse
model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R).
This member of the serotonin receptor family, crucially involved in the
regulation of brain structural plasticity and cognitive processes, can be
stimulated by systemic repeated treatment with LP-211, a brain-penetrant
selective agonist. The present study extends previous findings by demonstrating
that LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues mitochondrial
respiratory chain impairment, oxidative phosphorylation deficiency and the
reduced energy status in the brain of heterozygous female mice from two highly
validated mouse models of RTT (MeCP2-308 and MeCP2-Bird mice). Moreover, LP-211
treatment completely restored the radical species overproduction by brain
mitochondria in the MeCP2-308 model and partially recovered the oxidative
imbalance in the more severely affected MeCP2-Bird model. These results provide
the first evidence that RTT brain mitochondrial dysfunction can be rescued
targeting the brain 5-HT7R and add compelling preclinical evidence of the
potential therapeutic value of LP-211 as a pharmacological approach for this
devastating neurodevelopmental disorder.
PMID- 28419873
TI - Arrestin-2 and arrestin-3 differentially modulate locomotor responses and
sensitization to amphetamine.
AB - Arrestins play a prominent role in shutting down signaling via G protein-coupled
receptors. In recent years, a signaling role for arrestins independent of their
function in receptor desensitization has been discovered. Two ubiquitously
expressed arrestin isoforms, arrestin-2 and arrestin-3, perform similarly in the
desensitization process and share many signaling functions, enabling them to
substitute for one another. However, signaling roles specific to each isoform
have also been described. Mice lacking arrestin-3 (ARR3KO) were reported to show
blunted acute responsiveness to the locomotor stimulatory effect of amphetamine
(AMPH). It has been suggested that mice with deletion of arrestin-2 display a
similar phenotype. Here we demonstrate that the AMPH-induced locomotion of male
ARR3KO mice is reduced over the 7-day treatment period and during AMPH challenge
after a 7-day withdrawal. The data are consistent with impaired locomotor
sensitization to AMPH and suggest a role for arrestin-3-mediated signaling in the
sensitization process. In contrast, male ARR2KO mice showed enhanced early
responsiveness to AMPH and the lack of further sensitization, suggesting a role
for impaired receptor desensitization. The comparison of mice possessing one
allele of arrestin-3 and no arrestin-2 with ARR2KO littermates revealed reduced
activity of the former line, consistent with a contribution of arrestin-3
mediated signaling to AMPH responses. Surprisingly, ARR3KO mice with one arrestin
2 allele showed significantly reduced locomotor responses to AMPH combined with
lower novelty-induced locomotion, as compared to the ARR3KO line. These data
suggest that one allele of arrestin-2 is unable to support normal locomotor
behavior due to signaling and/or developmental defects.
PMID- 28419875
TI - Falls in people with Parkinson's disease: A prospective comparison of community
and home-based falls.
AB - BACKGROUND: Falls are common and debilitating in people with Parkinson's disease
(PD) and restrict participation in daily activities. Understanding circumstances
of falls in the community and at home may assist clinicians to target therapy
more effectively. OBJECTIVE: To compare the characteristics of community and home
fallers and the circumstances that contribute to falls in people living with PD.
METHODS: People with mild-moderately severe PD (n=196) used a daily falls diary
and telephone hotline to report prospectively the occurrence, location and
circumstances of falls over 14 months. RESULTS: 62% of people with PD fell, with
most falling at least once in the community. Compared to people who fell at home,
the community-only fallers had shorter durations of PD (p=0.012), less severe
disease (p=0.008) and reported fewer falls in the year prior to the study
(p=0.003). Most falls occurred while people were ambulant, during postural
transitions and when medication was working well. Community-based falls were
frequently attributed to environmental factors such as challenging terrains
(p<0.001), high attention demands (p=0.029), busy or cluttered areas (p<0.001)
and tasks requiring speed (p=0.020). Physical loads were more often present in
home than community-based falls (p=0.027). CONCLUSION: Falls that occur in the
community typically affect people with earlier PD and less severe disease than
home-based falls. Individuals experiencing community-based falls may benefit from
physiotherapy to manage challenging environments and high attention demands.
PMID- 28419874
TI - Oral administration of a specific kynurenic acid synthesis (KAT II) inhibitor
attenuates evoked glutamate release in rat prefrontal cortex.
AB - Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict
patient outcome; however, they remain poorly treated by current antipsychotic
drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative
allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are
commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ.
When acutely or chronically elevated in rodents, KYNA produces cognitive deficits
similar to those seen in the disease, making down-regulation of KYNA, via
inhibition of kynurenine aminotransferase II (KAT II), a potential treatment
strategy. We determined, in adult Wistar rats, if the orally available KAT II
inhibitor BFF816 a) prevents KYNA elevations in prefrontal cortex (PFC) after a
systemic kynurenine injection and b) reverses the kynurenine-induced attenuation
of evoked prefrontal glutamate release caused by stimulation of the nucleus
accumbens shell (NAcSh). Systemic injection of kynurenine (25 or 100 mg/kg, i.p.)
increased KYNA levels in PFC (532% and 1104% of baseline, respectively). NMDA
infusions (0.15 MUg/0.5 MUL) into NAcSh raised prefrontal glutamate levels more
than 30-fold above baseline. The two doses of kynurenine reduced evoked glutamate
release in PFC (by 43% and 94%, respectively, compared to NMDA alone). Co
administration of BFF816 (30 or 100 mg/kg, p.o.) with kynurenine (25 mg/kg, i.p.)
attenuated the neosynthesis of KYNA and dose-dependently restored NMDA-stimulated
glutamate release in the PFC (16% and 69%, respectively). The ability to prevent
KYNA neosynthesis and to normalize evoked glutamate release in PFC justifies
further development of KAT II inhibitors for the treatment of cognitive deficits
in SZ.
PMID- 28419876
TI - Reproducibility of the Balance Evaluation Systems Test (BESTest) and the Mini
BESTest in school-aged children.
AB - This study evaluated the intra-rater, inter-rater and test-retest reproducibility
of the Full-BESTest and Mini-BESTest when assessing postural control in children.
Thirty-four children aged 7-17 years participated in intra-rater and inter-rater
evaluation, and 22 children repeated assessment six weeks later for evaluation of
test-retest reliability. Postural control was assessed using the Full Balance
Evaluation Systems Test (Full-BESTest) and the short-form Mini-BESTest. Intra
rater, inter-rater and test-retest reproducibility were examined using video
assessment. Test-retest reproducibility was also assessed in real-time.
Reproducibility was examined by agreement and reliability statistics. Agreement
was calculated using percentage of agreement, Limits of Agreement and Smallest
Detectable Change. Reliability was calculated using Intra-class Correlation
Coefficients. Results showed that the reliability of Total Scores was excellent
for the Full-BESTest for all conditions (all ICCs>0.82), whereas the Mini-BESTest
ranged from fair to excellent (ICC=0.56-0.86). Percentage of Domain Scores with
good-excellent reliability (ICCs>0.60) was slightly higher for the Full-BESTest
(66%) compared to the Mini-BESTest (59%). Smallest Detectable Change scores were
good to excellent for the Full-BESTest (2%-6%) and for the Mini-BESTest (5%-10%)
relative to total test scores. Both the Full-BESTest and Mini-BESTest can
discriminate postural control abilities within and between days in school-aged
children. The Full-BESTest has slightly better reproducibility and a broader
range of items, which could be the most useful version for treatment planning. We
propose minor modifications to improve reproducibility for children, and indicate
the modified version by the title Kids-BESTest. Future psychometric research is
recommended for specific paediatric clinical populations.
PMID- 28419877
TI - Effect of foot orthoses on the medial longitudinal arch in children with flexible
flatfoot deformity: A three-dimensional moment analysis.
AB - Foot orthoses are often used to correct altered gait patterns. The purpose of
this study was to investigate how foot orthoses can modify the magnitude of three
dimensional moments of ankle, knee, and hip joints during a stride of gait in
children with flexible flat feet. Bilateral gait data were collected from
fourteen male children (age 10.2+/-1.4 years) suffering from flat feet syndrome.
In order to obtain the kinematics data, a Vicon system with six cameras (100Hz)
was used and two Kistler force plates (1000Hz) to record the kinetics data under
each leg. Arc support foot orthoses were used as an intervention. Paired-sample T
test was used for within-group comparisons (alpha=0.05). The results of data
analysis showed that foot orthoses can decrease the ankle evertor moment, knee
and hip abductor moments and hip flexor moment in dominant lower limb. In non
dominant lower limb, using the orthoses can decrease evertor and internal rotator
moments at the ankle, flexor and internal rotator moments at the knee and
extensor moment at the hip, while it can increase dorsiflexor moment at the
ankle. The findings imply that effects of orthoses on three dimensional moments
differ in dominant and non-dominant lower limbs. Furthermore, results
demonstrated that dominant and non-dominant lower limbs would also show different
responses to the same intervention.
PMID- 28419878
TI - Effect of Gross Total Resection in World Health Organization Grade II
Astrocytomas: SEER-Based Survival Analysis.
AB - INTRODUCTION: We sought to compare the survival benefit associated with gross
total resection (GTR) in World Health Organization grade II astrocytomas (A2)
with those of grade III (A3) and grade IV (glioblastoma) astrocytomas. METHODS:
Using the Surveillance, Epidemiology, and End Results program database (1999
2010), we identified 4113 A2 patients. Surgical resection was defined as GTR,
subtotal resection (STR), or no resection. Kaplan-Meier and multivariate Cox
proportional hazards analyses were used to assess survival with respect to extent
of resection. Results were compared with the benefit of GTR over STR in 2755 A3
and 21,962 glioblastoma patients from the same database. RESULTS: A multivariate
Cox proportional hazards analysis indicated that A2 patients who underwent a GTR
had a 28.3% reduction in the hazard of death relative to A2 patients who
underwent STR. Similar risk reductions were observed in A2 patients age <50 and
>=50. However, because of differences in the natural history of these cohorts,
the relative hazard reduction translated into distinct overall survival profiles.
For A2 patients >=50 years old, the GTR-associated survival benefit was
approximately 6 months, resembling that observed in glioblastoma patients. In
contrast, GTR in A2 patients <50 years old was associated with survival profiles
superior to those observed in A3 patients. CONCLUSIONS: In the Surveillance,
Epidemiology, and End Results (SEER) program database, GTR-associated survival
benefit in A2 patients >=50 years old resembled that observed in glioblastoma,
while GTR in A2 patients <50 years old was associated with a distinctly more
favorable survival profile.
PMID- 28419879
TI - Challenging the Myth of Right Nondominant Hemisphere: Lessons from
Corticosubcortical Stimulation Mapping in Awake Surgery and Surgical
Implications.
AB - For many years, the right hemisphere (RH) was considered as nondominant,
especially in right-handers. In neurosurgical practice, this dogma resulted in
the selection of awake procedure with language mapping only for lesions of the
left dominant hemisphere. Conversely, surgery under general anesthesia (possibly
with motor mapping) was usually proposed for right lesions. However, when
objective neuropsychological assessments were performed, they frequently showed
cognitive and behavioral deficits after brain surgery, even in the RH. Therefore,
to preserve an optimal quality of life, especially in patients with a long
survival expectancy (as in low-grade gliomas), awake surgery with cortical and
axonal electrostimulation mapping has recently been proposed for resection of
right tumors. Here, we review new insights gained from intraoperative stimulation
into the pivotal role of the RH in movement execution and control, visual
processes and spatial cognition, language and nonverbal semantic processing,
executive functions (e.g., attention), and social cognition (mentalizing and
emotion recognition). These original findings, which break with the myth of a
nondominant RH, may have important implications in cognitive neurosciences, by
improving our knowledge of the functional connectivity of the RH, as well as for
the clinical management of patients with a right lesion. In brain surgery, awake
mapping should be considered more systematically in the RH. Moreover,
neuropsychological examination must be achieved in a more systematic manner
before and after surgery within the RH, to optimize care by predicting the
likelihood of functional recovery and by elaborating specific programs of
rehabilitation.
PMID- 28419880
TI - Trepanation Practices in Asclepieia: Systematizing a Neurosurgical Innovation.
AB - BACKGROUND: As ancient Greeks started looking for deities that could fulfill the
pragmatic needs of common people, local heroes started being mythologized and
worshipped through cults. METHODS: The most widespread such example was
Asclepius, possibly a skilled war surgeon who followed military expeditions to
Colchis and Troy. Our study investigates the possibility of the early
neurosurgery to have been started inside Asclepieia by Asclepius and his
followers. RESULTS: Asclepius was worshipped at religious temples called
Asclepieia where certain specific medical and surgical techniques were followed.
The most advanced technique was skull trepanation, which was most likely done as
an acute operation to release intracranial pressure. The contemporary Hippocratic
corpus provided extensive descriptions of the technique, and archaeologic
evidence has shown that many patients survived the operation. CONCLUSIONS:
Decompressive craniectomy techniques have been practiced for millennia but it is
possible that they were first systematized as a neurosurgical innovation through
the Ancient Greek religious cult followed in Asclepieia.
PMID- 28419881
TI - The Effects of Clinical Factors and Retro-Odontoid Soft Tissue Thickness on
Atlantoaxial Instability in Patients with Rheumatoid Arthritis.
AB - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that often occurs
in the atlantoaxial segment of the cervical spine and results in instability that
can cause severe pain and neurologic symptoms. Thickening of soft tissue
posterior to the odontoid process of the atlantoaxial segment is referred to as
retro-odontoid soft tissue (ROST) thickness or pseudotumor. The mechanism of ROST
thickness is still unknown. METHODS: Among patients diagnosed with RA, those with
cervical radiographs and magnetic resonance imaging records were selected for
investigation of their clinical symptoms, laboratory findings, radiologic
evaluation, and RA medication history. RESULTS: A total of 199 patients were
selected and divided into lower and upper median groups according to the ROST
thickness value. In patients with RA, the median ROST thickness value was 2.3 mm
(interquartile range, 1.4-3.4). The median value of the anterior atlanto-dens
interval (ADI) was 2.4 mm, with a significant difference being observed between
the lower and upper median ROST thickness groups (P = 0.001). Multivariable
linear regression analysis revealed a correlation between Steinbrocker stage and
the positivity of rheumatoid factor. For each unit increase in the Steinbrocker
stage, the ROST thickness increased by 0.35 mm (beta, -0.349; 95% confidence
interval -0.643 to -0.055; P = 0.020). For every 1-mm increase in the ADI, ROST
thickness decreased by 0.16 mm (beta, -0.163; 95% confidence interval -0.264 to
0.062; P = 0.002). CONCLUSIONS: This study showed a statistical correlation
between ROST thickness and ADI related to biomechanical changes in the dynamic
atlantoaxial segment, thereby suggesting the value of a prospective study.
PMID- 28419882
TI - Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a
Chinese girl with Fanconi Anemia.
AB - Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known
complement groups caused by mutations in different genes. FA complementation
group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant
variants in the FANCL gene were documented. Phenotype and genotype correlation in
FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L
caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in
the FANCL gene. The patient's clinical course was typical for FA with progression
to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at
9 years of age. Mutation analysis also detected a likely somatic c.2608G > A
(p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and
gains of 3q and 21q and accumulated non-clonal single cell chromosomal
abnormalities were detected in blood leukocytes as her FA progressed. This is the
first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene
mutation and copy number aberrations could be used to monitor disease progression
and the clinical findings provide further information for genotype-phenotype
correlation for FA-L.
PMID- 28419883
TI - Feasibility and safety of foam sclerotherapy followed by a multiple
subcutaneously interrupt ligation under local anaesthesia for outpatients with
varicose veins.
AB - PURPOSE: To prospectively evaluate the feasibility and safety of foam
sclerotherapy and ligation (FSL) for outpatients with varicose veins under local
anaesthesia. METHODS: 136 outpatients with varicose veins who were unwilling to
be hospitalized underwent FSL. FSL is a technique in which the dilated varicose
veins were ligated subcutaneously after foam sclerotherapy with an absorbable
suture. Patients were reviewed at 1, 3, 6 and 12 months after FSL. Pain scores
were recorded after FSL. The revised venous clinical severity scorer (rVCSS) and
clinical, etiological, anatomical, and pathological classification (CEAP) were
used to evaluate the improvement at 3 months after treatment. RESULTS: 146 limbs
in 136 outpatients with varicose veins were managed with FSL. The pain scores
decreased following FSL, CEAP classification score, the rVCSS values improved 3
months postintervention. No significant postoperative complications were observed
on follow-up. CONCLUSION: FSL is feasible, safe and easily to perform under local
anaesthesia for outpatients with varicose veins.
PMID- 28419884
TI - Fish oil supplementation for primary prevention of atrial fibrillation after
coronary artery bypass graft surgery: A randomized clinical trial.
AB - BACKGROUND: Atrial fibrillation (AF) after cardiac surgery is a common
complication that may influence patients' early and long term outcomes and
hospital costs. The purpose of this study was to assess the effect of fish oil on
occurrence of AF following coronary artery bypass graft surgery (CABG). METHODS:
This study was a single-center, randomized, double blinded, placebo-controlled
clinical trial. Four-hundred and one patients undergoing coronary artery bypass
graft surgery were randomly assigned to receive 2 g/d fish oil or placebo (olive
oil) for at least 5 days before surgery. The primary end point was defined as
time to AF improvement After AF incidence following isolated CABG or a need for
pharmacologic therapy or cardioversion. RESULTS: The time to AF improvement in
intervention group was shorter than control group (HR: 2.05; 95% CI = 0.70-6.22,
P = 0.20). The incidence of AF in the intervention and control groups was 8.40%
vs. 14.07% respectively (p = 0.07). Mean total duration of AF was 20.96 +/- 4.71
h in intervention groups and 46.87 +/- 7.44 h in control groups (p = 0.04). Mean
duration of stay in the ICU and total hospital stay showed a significant
reduction in the intervention group (p = 0.003 and p = 0.04, respectively).
CONCLUSION: The consumption of PUFA leads to a shorter time to AF improvement,
which was not statistically significant. The incidence of AF in patients
undergoing CABG surgery was decreased by approximately 5.7%; which was
statistically on the borderline. Fish oil reduced median length of stay in the
ICU and hospital. Further well-designed studies are needed to overcome the
limitations of the existing trials and provide conclusive conclusions.
PMID- 28419885
TI - Registry of implants for the reconstruction of pelvic floor in males and females:
A feasibility case series.
AB - INTRODUCTION: Most aspects of implant-assisted reconstruction of pelvic floor in
males and females are under debate and the research is not standardized.
Registries are supposed to shed light to the indications, surgical techniques and
material properties and to establish a standardized evaluation. METHODS: A
working group was formed to create an online platform for registration and
outcome measurement of implant-assisted operations for pelvic organ prolapse
(POP) and female and male stress urinary incontinence (SUI). 20 patients with
modified mesh materials were evaluated over 23 months follow up in the registry
to prove the feasibility of the registry. For validation a previously published
modified "satisfaction, anatomy, continence, safety - S.(A.)C.S score" was used.
RESULTS: A consensus was met on definitions and classifications of patient
variables, surgical procedures and implants, as well as outcome parameters
(efficacy, continence, satisfaction, complications). Different subgroup modules
were formed in accordance with treated condition. The maximum score of cure was
reached by 25-100% of patients depending on the indication. CONCLUSION: A
prospective registry in accordance with IDEAL-D framework is justified for the
evaluation and regulation of implants for pelvic floor reconstruction.
PMID- 28419886
TI - Total hip arthroplasty for patients with Crowe type IV developmental dysplasia of
the hip: Ten years results.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the rate of
union, functional results and complications in patients with Crowe IV
developmental dysplasia of the hip (DDH) who underwent cementless total hip
arthroplasty (THA) with S-ROM prostheses and subtrochanteric transverse
shortening osteotomy. METHODS: Forty-five patients (52 hips) operated between
January 2005 and May 2008, with a mean age of 40.6 years at surgery were
followed. The mean follow-up period was 9.8 years. Clinical outcomes,
radiographic outcomes and complications were evaluated. RESULTS: Osteotomy union
occurred in 52 of 52 femurs (100%). Mean Harris hip score improved from 33.7 +/-
4.7 preoperatively to 81.2 +/- 6.3, 90.8 +/- 5.3 and 89.8 +/- 7.1 at 1, 5 and 10
years postoperatively. Two patients had temporary sciatic nerve paralysis
postoperatively, and 2 patients experienced early postoperative dislocation. Two
patients complained about mild longer limb length than the non-operated limb at
the last follow-up. Three hips showed osteolysis in Gruen zone 1, and 1 hip
showed osteolysis in zone 1 and 7. No implants were revised, and no signs of
component loosening and migration were observed at the last follow-up visit.
CONCLUSIONS: S-ROM stem combined with transverse subtrochanteric shortening
osteotomy in THA for patients with Crowe type IV DDH has good clinical results
with small risk of complications.
PMID- 28419887
TI - Unpacking the impact of adverse childhood experiences on adult mental health.
AB - Exposure to childhood adversity has an impact on adult mental health, increasing
the risk for depression and suicide. Associations between Adverse Childhood
Experiences (ACEs) and several adult mental and behavioral health outcomes are
well documented in the literature, establishing the need for prevention. The
current study analyzes the relationship between an expanded ACE score that
includes being spanked as a child and adult mental health outcomes by examining
each ACE separately to determine the contribution of each ACE. Data were drawn
from Wave II of the CDC-Kaiser ACE Study, consisting of 7465 adult members of
Kaiser Permanente in southern California. Dichotomous variables corresponding to
each of the 11 ACE categories were created, with ACE score ranging from 0 to 11
corresponding to the total number of ACEs experienced. Multiple logistic
regression modeling was used to examine the relationship between ACEs and adult
mental health outcomes adjusting for sociodemographic covariates. Results
indicated a graded dose-response relationship between the expanded ACE score and
the likelihood of moderate to heavy drinking, drug use, depressed affect, and
suicide attempts in adulthood. In the adjusted models, being spanked as a child
was significantly associated with all self-reported mental health outcomes. Over
80% of the sample reported exposure to at least one ACE, signifying the potential
to capture experiences not previously considered by traditional ACE indices. The
findings highlight the importance of examining both cumulative ACE scores and
individual ACEs on adult health outcomes to better understand key risk and
protective factors for future prevention efforts.
PMID- 28419888
TI - Zika, sexual transmission and prudent public health policy.
PMID- 28419889
TI - Studies on the 6-homologation of beta-D-idopyranosides.
AB - beta-D-Idopyranosides are interesting sugars because of their unusual
conformational flexibility in the pyranosyl ring, and also their beta-1,2-cis
anomeric configuration. Here we report our studies of the regioselective opening
of 4,6-O-benzylidene-protected beta-D-idopyranosides under reducing conditions,
and the subsequent 6-homologation via Swern oxidation and Wittig olefination to
afford a 6,7-dideoxy-beta-D-ido-hept-6-enopyranoside. This olefination product
was found to adopt predominantly 1C4 conformation in solution by NMR experiments,
which places the vinyl group at a more sterically hindered axial position and
creates difficulty in subsequent hydroborations.
PMID- 28419890
TI - Pragmatic trial of a Study Navigator Model (NAU) vs. Ambassador Model (N+) to
increase enrollment to health research among community members who use illicit
drugs.
AB - BACKGROUND: Although drug use is common in the population, drug users are
sometimes excluded from research without justification. Two models of
individualized study matching were compared for effectiveness in enrolling people
who "endorsed current drug use" and those who "did not" into appropriate
research. METHODS: Participants in the NIDA-funded Transformative Approach to
Reduce Research Disparities Towards Drug Users study (Navigation Study) were
recruited through a Clinical and Translational Science Award (CTSA) community
engagement model. Of the 614 community-recruited adults, 326 endorsed current
drug use (cases); 288 did not (controls). Participants were randomized to one of
two intervention groups: Navigation as Usual (NAU) [individualized study matching
through a Study Navigator] or Enhanced Navigation (N+) [individualized study
matching plus transportation and other assistance through an Ambassador]. Rates
of enrollment into research studies were compared. RESULTS: At 90 days, N+ vs.
the NAU intervention was associated with higher enrollment among both drug users
(36.0% N+ vs. 24.9% NAU) and non-drug users (45.5% N+ vs. 25.2% NAU). NAU
attained the same rate of enrollment for users of drugs (24.9%) and non-users
(25.2%); N+ had similar rates as well (36.0% drug users vs. 45.5% non-drug
users). In addition, high rates of enrollment were achieved among all groups of
participants, from 24.9% (drug users in NAU) to 45.5% (non-drug users in N+).
CONCLUSIONS: Both the NAU and N+ methods can reduce barriers and help users and
non-users become part of the population that participates in research. Working
with the local CTSA adds significant value to the research enterprise.
PMID- 28419891
TI - I care, even after the first impression: Facial appearance-based evaluations in
healthcare context.
AB - PURPOSE: Prior research has demonstrated that healthcare providers' implicit
biases may contribute to healthcare disparities. Independent research in social
psychology indicates that facial appearance-based evaluations affect social
behavior in a variety of domains, influencing political, legal, and economic
decisions. Whether and to what extent these evaluations influence approach
behavior in healthcare contexts warrants research attention. Here we investigate
the impact of facial appearance-based evaluations of trustworthiness on
healthcare providers' caring inclination, and the moderating role of experience
and information about the social identity of the faces. METHOD: Novice and expert
nurses rated their inclination to provide care when viewing photos of trustworthy
, neutral-, and untrustworthy-looking faces. To explore whether information about
the target of care influences caring inclination, some participants were told
that they would view patients' faces while others received no information about
the faces. RESULTS: Both novice and expert nurses had higher caring inclination
scores for trustworthy-than for untrustworthy-looking faces; however, experts had
higher scores than novices for untrustworthy-looking faces. Regardless of a
face's trustworthiness level, experts had higher caring inclination scores for
patients than for unidentified individuals, while novices showed no differences.
CONCLUSIONS: Facial appearance-based inferences can bias caring inclination in
healthcare contexts. However, expert healthcare providers are less biased by
these inferences and more sensitive to information about the target of care.
These findings highlight the importance of promoting novice healthcare
professionals' awareness of first impression biases.
PMID- 28419892
TI - Plasma apolipoproteins and physical and cognitive health in very old individuals.
AB - Apolipoproteins play a crucial role in lipid metabolism with implications in
cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We
quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using
immunoassays and explored relationships with APOE polymorphism epsilon2/3/4,
vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH,
and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends.
Centenarians had the highest ApoE levels and the lowest frequency of APOE
epsilon4 allele relative to younger groups. Apolipoprotein levels trended lower
in APOE epsilon4 homozygotes and heterozygotes compared with noncarriers, with
ApoE and ApoJ being significantly lower. Levels of all apolipoproteins except
ApoH were higher in females. Sex- and age-related differences were apparent in
the association of apolipoproteins with cognitive performance, as only women had
significant negative associations of ApoB, ApoE, ApoH, and ApoJ in mid-life,
whereas associations at older age were nonsignificant or positive. Our findings
suggest levels of some apolipoproteins, especially ApoE, are associated with
lifespan and cognitive function in exceptionally long-lived individuals.
PMID- 28419893
TI - Carbon monoxide-related fatalities: A 60-year single institution experience.
AB - OBJECTIVE: Though carbon monoxide (CO) poisonings account currently for a
relatively small percentage of total non-natural deaths in Europe, they represent
a serious public health burden and significant component of avoidable mortality
in many countries. Our aim was to investigate long-term trends and to determine
epidemiologic characteristics of the CO-related deaths in the Czech Republic,
recorded at the Department of Forensic Medicine in Hradec Kralove. METHODS: This
was an autopsy-based single-centre retrospective cohort study of all fatalities
caused by CO poisoning over six decades (1947-2006). All data were numerically
evaluated and processed using NCSS 10 Statistical Software. Statistical
significance was defined as a p-value less than 0.05. RESULTS: A total of 1233 CO
related deaths were identified for inclusion in the study. The manner of death
was ranked in order as follows: 45% accidental poisoning, 40% suicidal poisoning,
1% homicidal poisoning, 14% remained undetermined. There were slightly more male
victims (59%) than female, and the mean age overall was 48 years. The majority of
CO-related fatalities were attributed to coal gas inhalation, with the remainder
being from inhaled motor vehicle exhaust fumes, inhaled fire smoke, and other
combustion sources such as charcoal, gas and wood-burning appliances. The mean
blood carboxyhemoglobin (COHb) level was 66%. A positive blood ethanol
concentration was measured in 455 (37%) cases examined. Non-intentional
poisonings were highly correlated with the winter months. CONCLUSION: This study
shows that the prevalence of CO-related deaths has decreased significantly in the
Czech Republic following the widespread detoxification of the domestic gas in the
1990-1995. Our findings suggest that acute ethanol use, poorer socioeconomic
position, and inadequate education status about the danger of CO are associated
with an increased risk of fatal CO poisoning. Finally, our results demonstrate
the continued value of the autopsy in monitoring global public health security
issues and socioeconomic situation. Further similar large-scale studies in
different populations are needed to improve the targeting of interventions to the
groups with the highest level of risk, and to understand the sources of variation
in CO-related mortality.
PMID- 28419895
TI - Electrochemical oxidation of iron and alkalinity generation for efficient sulfide
control in sewers.
AB - The addition of iron salts is one of the most commonly used dosing strategies for
sulfide control in sewers. However, iron salts decrease the sewage pH which not
only reduces the effectiveness of sulfide precipitation but also enhances the
release of residual sulfide to the sewer atmosphere. Equally important,
concentrated iron salt solutions are corrosive and their frequent transport,
handling, and on-site storage often come with Occupational Health and Safety
(OH&S) concerns. Here, we experimentally demonstrated a novel sulfide control
approach using electrochemical systems with parallel placed iron electrodes. This
enabled combining anodic dissolved iron species release with cathodic hydroxyl
anion production, which alleviates all the aforementioned concerns. A long-term
experiment was successfully carried out achieving an average sulfide removal
efficiency of 95.4 +/- 4.4% at low voltage input of 2.90 +/- 0.54 V over the
course of 8 weeks. This electrochemical method was demonstrated to successfully
achieve efficient sulfide control. In addition, it increases the sewage pH,
thereby overcoming the drawbacks associated with the pH decrease in the case of
conventional iron salt dosing. Ferrous ions were produced at an overall coulombic
efficiency (CE) of 98.2 +/- 1.2%, whereas oxygen evolution and direct sulfide
oxidation were not observed. Short-term experiments showed that increasing either
inter-electrode gap or current density increased the cell voltage associated with
the increase in the ohmic drop of the system. Overall, this study highlights the
practical potential of in-situ generation of dissolved iron species and
simultaneous hydroxyl anion generation for efficient sulfide control in sewers.
PMID- 28419896
TI - The use of diatoms in ecotoxicology and bioassessment: Insights, advances and
challenges.
AB - Diatoms are regularly used for bioassessment and ecotoxicological studies in
relation to environmental and anthropogenic disturbances. Traditional taxonomical
diatom parameters (cell counts, biovolume estimates, species richness, diversity
indices and metrics using sensitive and tolerant diatom species) are regularly
used for these studies. In the same context, very less focus was given on new
endpoints of diatoms (life-forms, nuclear anomalies, alteration in photosynthetic
apparatus shape, motility, lipid bodies, size reduction and deformities), in
spite of their numerous merits, such as, their easiness, quickness, cheapness,
global acceptation and no especial training in diatom taxonomy. In this review we
analyzed 202 articles (from lab and field studies), with the aim to investigate
the bioassessment and ecotoxicological advancement taken place in diatom research
especially in terms of exploring new endpoints along with the traditional
taxonomical parameters in a perspective which can greatly enhance the evaluation
of fluvial ecosystem quality for biomonitoring practices.
PMID- 28419897
TI - Nurse mentor perceptions in the delivery of a home-based cardiac rehabilitation
program to support patients living in rural areas: An interpretive study.
AB - Home-based cardiac rehabilitation (CR) programs improve health outcomes for
people diagnosed with heart disease. Mentoring of patients by nurses trained in
CR has been proposed as an innovative model of cardiac care. Little is known
however, about the experience of mentors facilitating such programs and adapting
to this new role. The aim of this qualitative study was to explore nurse mentor
perceptions of their role in the delivery of a home-based CR program for rural
patients unable to attend a hospital or outpatient CR program. Seven nurses
mentored patients by telephone providing patients with education, psychosocial
support and lifestyle advice during their recovery. An open-ended survey was
administered to mentors by email and findings revealed mentors perceived their
role to be integral to the success of the program. Nurses were satisfied with the
development of their new role as patient mentors. They believed their
collaborative skills, knowledge and experience in coronary care, timely support
and guidance of patients during their recovery and use of innovative audiovisual
resources improved the health outcomes of patients not able to attend traditional
programs. Cardiac nurses in this study perceived that they were able to
successfully transition from their normal work practices in hospital to mentoring
patients in their homes.
PMID- 28419894
TI - Muscle cell communication in development and repair.
AB - Under basal conditions, postnatal skeletal muscle displays little cell turnover.
With injury, muscle initiates a rapid repair response to reseal damaged membrane,
reactivating many developmental pathways to facilitate muscle regeneration and
prevent tissue loss. Muscle precursor cells become activated accompanied by
differentiation and fusion during both muscle growth and regeneration; inter
cellular communication is required for successful completion of these processes.
Cellular communication is mediated by lipids, fusogenic membrane proteins, and
exosomes. Muscle-derived exosomes carry proteins and micro RNAs as cargo.
Secreted factors such as IGF-1, TGFbeta, and myostatin are also released by
muscle cells providing local signaling cues to modulate muscle fusion and
regeneration. Proteins that regulate myoblast fusion also participate in membrane
repair and regeneration. Here we will review methods of muscle cell communication
focusing on proteins that mediate membrane fusion, exosomes, and autocrine
factors.
PMID- 28419898
TI - Theory-guided access to efficient photodegradation of the simplest
perfluorocarboxylic acid: Trifluoroacetic acid.
AB - The photodegradation approaches of perfluorocarboxylic acids have attracted
considerable attention and have been developed extensively. However, the reaction
channels along which the perfluorocarboxylic acid molecules dissociate remain to
be deciphered by means of the quantum chemical method at the electronically
excited state level of theory until now. Here we report the photodissociation
mechanism of the simplest perfluorocarboxylic acid, trifluoroacetic acid, using
the complete active space self-consistent field (CASSCF) and the multi
configurational second-order perturbation (CASPT2) methods. The CC and CO alpha
bond fission channels were both taken into account. Based on the constructed
potential energy surfaces, it is concluded that the CC alpha bond fission, which
would probably account for further degradations and mineralizations, may mainly
take place in the triplet manifolds via intersystem crossing from the S1 state.
Thus, taking the computational results of the simple member of
perfluorocarboxylic acids as a rational clue, strategies to enhance intersystem
crossing process efficiencies of the photodegradation of perfluorocarboxylic
acids can be developed.
PMID- 28419899
TI - The long term tsunami impact: Evolution of iron speciation and major elements
concentration in tsunami deposits from Thailand.
AB - The article describes the unique studies of the chemical composition changes of
new geological object (tsunami deposits in south Thailand - Andaman Sea Coast)
during four years (2005-2008) from the beginning of formation of it (deposition
of tsunami transported material, 26 December 2004). The chemical composition of
the acid leachable fraction of the tsunami deposits has been studied in the scope
of concentration macrocompounds - concentration of calcium, magnesium, iron,
manganese and iron speciation - the occurrence of Fe(II), Fe(III) and non-ionic
iron species described as complexed iron (Fe complex). The changes of chemical
composition and iron speciation in the acid leachable fraction of tsunami
deposits have been observed with not clear tendencies of changes direction. For
iron speciation changes the transformation of the Fe complex to Fe(III) has been
recorded with no significant changes of the level of Fe(II).
PMID- 28419900
TI - Dimethylarsenate (DMA) exposure influences germination rates, arsenic uptake and
arsenic species formation in wheat.
AB - The contamination of cereals with arsenic (As) is a global health and agronomic
concern. This study compared the physiological response, As uptake and As
speciation in the grains and above ground tissues of 20 wheat cultivars exposed
to 5 mg As kg-1 soil as either arsenate (AsV) or dimethylarsenate (DMA) under
glasshouse conditions. Germination rates for the majority of cultivars exceeded
80% for the majority of cultivars when exposed to AsV, but fell significantly to
20-40% when exposed to DMA. For a number of cultivars, grain yields were 20-50%
lower when plants were exposed to DMA compared to AsV. Grain As concentrations
were between 0.6 and 1.6 MUg As g-1 grain across the twenty cultivars when
exposed to AsV, whereas grain As concentrations were much higher (2.2-4.6 MUg As
g-1 grain) when exposed to DMA. When plants were exposed to AsV, 100% of the As
present in the grain was found as inorganic As while in plants exposed to DMA, 70
90% of As was present as DMA with the remainder found as inorganic As. DMA is
believed to be incorporated by plants via silica (Si) acid channels and
assessment of grain Si concentrations demonstrated that up to 40% less Si was
accumulated in grains when plants were exposed to DMA. The decreased germination
rates and grain yields in the presence of DMA is similar to the symptoms
described for straight head disease in rice, which has been linked to DMA
exposure. The results presented here indicate some analogous processes occur in
wheat to those described in rice. We hypothesise that exposure to DMA may have
inhibited Si-metabolism and translocation which resulted in both developmental
impairment and possibly an increased susceptibility to soil pathogens.
PMID- 28419901
TI - Does exclusion of cancers registered only from death-certificate information
diminish socio-demographic disparities in recorded survival?
AB - BACKGROUND: Death Certificate Only (DCO) cancer cases are commonly excluded from
survival analyses due to unknown survival time. This study examines whether socio
demographic factors are associated with DCO diagnosis, and the potential effects
of excluding DCO cases on socio-demographic cancer survival disparities in NSW,
Australia. METHODS: NSW Cancer Registry data for cases diagnosed in 2000-2008
were used in this study. Logistic regression was used to estimate the odds of DCO
registration by socio-demographic sub-group (socio-economic disadvantage,
residential remoteness, country of birth, age at diagnosis). Cox proportional
hazard regression was used to estimate the probability of death from cancer by
socio-demographic subgroup when DCO cases were included and excluded from
analyses. RESULTS: DCO cases consisted of 1.5% (n=4336) of all cases (n=299,651).
DCO diagnosis was associated with living in socio-economically disadvantaged
areas (most disadvantaged compared with least disadvantaged quintile: odds ratio
OR 1.25, 95%CI 1.12-1.40), living in inner regional (OR 1.16, 95%CI 1.08-1.25) or
remote areas (OR 1.48, 95%CI 1.01-2.19), having an unknown country of birth (OR
1.63, 95%CI 1.47-1.81) and older age. Including or excluding DCO cases had no
significant impact on hazard ratios for cancer death by socio-economic
disadvantage quintile or remoteness category, and only a minor impact on hazard
ratios by age. CONCLUSION: Socio-demographic factors were associated with DCO
diagnosis in NSW. However, socio-demographic cancer survival disparities remained
unchanged or varied only slightly irrespective of including/excluding DCO cases.
Further research could examine the upper limits of DCO proportions that
significantly alter estimated cancer survival differentials if DCOs are excluded.
PMID- 28419902
TI - Evaluating the efficacy of DNA differential extraction methods for sexual assault
evidence.
AB - Analysis of sexual assault evidence, often a mixture of spermatozoa and victim
epithelial cells, represents a significant portion of a forensic DNA laboratory's
case load. Successful genotyping of sperm DNA from these mixed cell samples,
particularly with low amounts of sperm, depends on maximizing sperm DNA recovery
and minimizing non-sperm DNA carryover. For evaluating the efficacy of the
differential extraction, we present a method which uses a Separation Potential
Ratio (SPRED) to consider both sperm DNA recovery and non-sperm DNA removal as
variables for determining separation efficiency. In addition, we describe how the
ratio of male-to-female DNA in the sperm fraction may be estimated by using the
SPRED of the differential extraction method in conjunction with the estimated
ratio of male-to-female DNA initially present on the mixed swab. This approach
may be useful for evaluating or modifying differential extraction methods, as we
demonstrate by comparing experimental results obtained from the traditional
differential extraction and the Erase Sperm Isolation Kit (PTC(c)) procedures.
PMID- 28419903
TI - DNA methylation-based age prediction from saliva: High age predictability by
combination of 7 CpG markers.
AB - DNA methylation is currently one of the most promising age-predictive biomarkers.
Many studies have reported DNA methylation-based age predictive models, but most
of these are based on DNA methylation patterns from blood. Only a few studies
have examined age-predictive DNA patterns in saliva, which is one of the most
frequently-encountered body fluids at crime scenes. In this study, we generated
genome-wide DNA methylation profiles of saliva from 54 individuals and identified
CpG markers that showed a high correlation between methylation and age. Because
the age-associated marker candidates from saliva differed from those of blood, we
investigated DNA methylation patterns of 6 age-associated CpG marker candidates
(cg00481951, cg19671120, cg14361627, cg08928145, cg12757011, and cg07547549 of
the SST, CNGA3, KLF14, TSSK6, TBR1, and SLC12A5 genes, respectively) in addition
to a cell type-specific CpG marker (cg18384097 of the PTPN7 gene) in an
independent set of saliva samples obtained from 226 individuals aged 18 to 65
years. Multiplex methylation SNaPshot reactions were used to generate the data.
We then generated a linear regression model with age information and the
methylation profile from the 113 training samples. The model exhibited a 94.5%
correlation between predicted and chronological age with a mean absolute
deviation (MAD) from chronological age of 3.13 years. In subsequent validation
using 113 test samples, we also observed a high correlation between predicted and
chronological age (Spearman's rho=0.952, MAD from chronological age=3.15years).
The model composed of 7 selected CpG sites enabled age prediction in saliva with
high accuracy, which will be useful in saliva analysis for investigative leads.
PMID- 28419904
TI - Leydig cell tumor in grey zone: A case report.
AB - INTRODUCTION: Leydig cell tumor constitutes only about 1-3% of testicular
neoplasms. There is apparently increased incidence in the last few years; one
possible explanation for this phenomenon is the widespread use of ultrasound
technology and the subsequent increased early detection of smaller lesions that
have not been found in historical series. CASE PRESENTATION: We report a case of
Leydig cell tumor of testis in a patient presenting with painless long standing
slowly growing left scrotal mass who found to have intrapulmonary nodule and
multiple enlarged retroperitoneal lymph nodes on staging work up. The mass was
managed by radical orchiectomy. Pathological diagnosis was Leydig cell tumor.
DISCUSSION: Orchiectomy is the accepted mode of treatment but follow-up every 3-6
months with physical examination, hormone assays, scrotal and abdominal
ultrasonography, chest radiography, and CT scans is essential in such a case with
a potential for malignant behavior. CONCLUSION: Inguinal orchiectomy is the
therapeutic decision of choice and long-term follow-up is necessary to exclude
recurrence or metastasis. Cases which fall in the grey zone like ours need to be
followed up carefully for metastasis instead of rushing into an early
retroperitoneal lymph node dissection, with its potential risks and
complications.
PMID- 28419905
TI - Spontaneous perforation of common bile duct in a young female: An intra-operative
surprise.
AB - INTRODUCTION: Spontaneous CBD perforation is one of the rare causes of acute
abdomen in infants and extremely rare in adults. It is rarely suspected and
correctly diagnosed preoperatively. PRESENTATION OF CASE: A 17year old female
presented to Emergency Department with sudden onset of pain and distention of
abdomen, associated with vomiting and non-passage of flatus and stool for 3days
and features of generalized peritonitis. On exploration, a perforation of size
0.5cm in diameter was present on the antero-lateral surface of supraduodenal part
of common bile duct (CBD) below the junction of cystic duct and common hepatic
duct. Cholecystectomy done and the CBD repaired over a T-tube. DISCUSSION:
Spontaneous perforation of bile duct should ideally manage with T-tube drainage
of the CBD along with cholecystectomy. In case with distal obstruction of the
CBD, a biliary enteric bypass should be done. CONCLUSION: Due to the paucity of
cases, the index of suspicion for this diagnosis is low. But bilious peritoneal
tap, features of generalized peritonitis and absence of free gas under diaphragm
in abdominal x-ray may be considered as clues for suspicion. Accordingly, Surgery
remains the mainstay of treatment.
PMID- 28419906
TI - Plant hormone signaling in flowering: An epigenetic point of view.
AB - Reproduction is one of the most important phases in an organism's lifecycle. In
the case of angiosperm plants, flowering provides the major developmental
transition from the vegetative to the reproductive stage, and requires genetic
and epigenetic reprogramming to ensure the success of seed production. Flowering
is regulated by a complex network of genes that integrate multiple environmental
cues and endogenous signals so that flowering occurs at the right time; hormone
regulation, signaling and homeostasis are very important in this process. Working
alone or in combination, hormones are able to promote flowering by epigenetic
regulation. Some plant hormones, such as gibberellins, jasmonic acid, abscisic
acid and auxins, have important effects on chromatin compaction mediated by DNA
methylation and histone posttranslational modifications, which hints at the role
that epigenetic regulation may play in flowering through hormone action. miRNAs
have been viewed as acting independently from DNA methylation and histone
modification, ignoring their potential to interact with hormone signaling -
including the signaling of auxins, gibberellins, ethylene, jasmonic acid,
salicylic acid and others - to regulate flowering. Therefore, in this review we
examine new findings about interactions between epigenetic mechanisms and key
players in hormone signaling to coordinate flowering.
PMID- 28419908
TI - Editorial overview: Characterizing the cancer genome: mechanistic insights and
translational opportunities.
PMID- 28419907
TI - FLC expression is down-regulated by cold treatment in Diplotaxis tenuifolia (wild
rocket), but flowering time is unaffected.
AB - Wild rocket (Diplotaxis tenuifolia) has become a very popular salad leaf due to
its peppery taste. It is part of the Brassicaceae family and thus has a high
level of homology at the DNA level to other Brassica species including
Arabidopsis thaliana. The vernalization and photoperiodic requirements of wild
rocket have not been reported to date. Photoperiodic experiments described here
demonstrate that rocket is a facultative long day plant. To investigate the
vernalization requirement, both seed and young plants were given vernalization
treatments at 4 degrees C for different lengths of time. A rocket homologue of
FLOWERING LOCUS C (DtFLC) was isolated and shown to functionally complement the
Arabidopsis FRI+flc3 null mutant. Whilst the expression of DtFLC was
significantly reduced after just one week of cold treatment, cold treatments of
two to eight weeks had no significant effect on bolting time of wild rocket
indicating that rocket does not have a vernalization requirement. These findings
illustrate that important fundamental differences can exist between model and
crop plant species, such as in this case where down-regulation of DtFLC
expression does not enable earlier flowering in wild rocket as it does in
Arabidopsis and many other Brassica species.
PMID- 28419909
TI - Reduction in advanced breast cancer after introduction of a mammography screening
program in Tyrol/Austria.
AB - BACKGROUND: We analysed all female breast cancer (BC) cases in Tyrol/Austria
regarding the shift in cancer characteristics, especially the shift in advanced
BC, for the group exposed to screening as compared to the group unexposed to
screening. METHODS: The analysis was based on all BC cases diagnosed in women
aged 40-69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The
data were linked to the Tyrolean mammography screening programme database to
classify BC cases as "exposed to screening" or "unexposed to screening". Age
adjusted relative risks (RR) were estimated by relating the exposed to the
unexposed group. RESULTS: In a total of about 145,000 women aged 40-69 years
living in Tyrol during the study period, 1475 invasive BC cases were registered.
We estimated an age-adjusted relative risk (RR) for tumour size >= 21 mm of 0.72
(95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI
0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing
those exposed to those unexposed to screening, respectively. CONCLUSION: In our
population-based registry analysis we observed that participation in the
mammography screening programme in Tyrol is associated with a 28% decrease in
risk for BC cases with tumour size >= 21 mm and a 17% decrease in risk for
advanced BC. We therefore expect the Tyrolean mammography programme to show a
reduction in BC mortality.
PMID- 28419910
TI - Endometriosis doubles odds for miscarriage in patients undergoing IVF or ICSI.
AB - OBJECTIVE: To identify and estimate the importance of risk factors on pregnancy
loss until the end of the second trimester after clinical pregnancy was achieved
by either in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection
(ICSI). STUDY DESIGN: Retrospective cohort study including 588 cycles with fresh
embryo transfers and 150 cycles with frozen-thawed embryo transfers using
logistic regression. RESULTS: The rate of miscarriages subsequent to a fresh
embryo transfer was significantly increased by a diagnosis of endometriosis
(p=0.02), as well as significantly influenced by the age of the female patient at
the time of oocyte retrieval (p<0.01) and the serum level of testosterone
(p=0.02). The time between freezing and thawing of the pronuclear stages for a
frozen-thawed embryo transfer revealed a trend to a higher rate of miscarriages
(p=0.06). CONCLUSION: Endometriosis significantly decreases the chance of having
a baby even with IVF or ICSI.
PMID- 28419911
TI - Safety and long-term efficacy of fractional CO2 laser treatment in women
suffering from genitourinary syndrome of menopause.
AB - OBJECTIVES: To evaluate the safety and long-term efficacy of fractional CO2 laser
treatment in reducing the severity of symptoms of genitourinary syndrome of
menopause (GSM) in menopausal women. STUDY DESIGN: 102 women presenting with
symptomatic GSM were treated with the fractional CO2 laser (MonaLisa Touch, DEKA)
system across a series of treatments delivered at intervals of six or more weeks.
The Australian Pelvic Floor Questionnaire was used to gather data on sexual
function and side-effects at three time-points across the study period
(prospective panel design study). Wilcoxon signed-rank tests were used to detect
statistically and clinically significant changes in sexual function and side
effects occurring from pre- to post-treatment. The primary outcome of this study
was an improvement of the symptoms of GSM. The secondary outcome included bladder
function and prolapse symptoms. RESULTS: A total of 102 women suffering from
moderate to severe GSM were recruited. Eighty-four percent experienced
significant improvement in their symptoms after CO2 laser treatment. Scores on
measures of sexual function, dyspareunia, and bothersomeness of sexual issues
were improved from pre-treatment to long-term (12-24 month) follow-up.
Furthermore, there were improvements on measures of bladder function (P=0.001),
prolapse (P=0.001), vaginal sensation (P=0.001), vaginal lubrication (P<0.001)
and urge incontinence (P=0.003) from the pre-treatment assessment to the second
assessment (i.e. after the third treatment). CONCLUSIONS: In this study,
fractional microablative CO2 laser treatment was associated with an improvement
in symptoms of GSM and sexual function.
PMID- 28419912
TI - The mucosal pellicle - An underestimated factor in oral physiology.
AB - Bioadhesion and bio-adsorption of proteins, glycoproteins and other biomolecules
are ubiquitous phenomena in the oral cavity. While the protective role of the
adsorbed salivary biomolecules on teeth (the acquired enamel pellicle) is well
established, it has yet to be defined whether comparable processes occur on the
desquamating oral soft tissues. The general term for these layers is pellicle,
but due to the different characteristics of the coated surfaces the enamel
pellicle and mucosal pellicle are their own entities. There is considerable
information on the enamel pellicle, whereas only limited data are available on
the mucosal pellicle. This can be attributed to the difficult standardized
preparation of this biological structure. Based on the present knowledge the
abundant and characteristic components of the mucosal pellicle include secreted
soluble mucins (MUC5B, MUC7), membrane-associated epithelial mucins (MUC1), and
to a lesser degree CA VI, sIgA, and cystatin. However, it seems to be of
completely different ultrastructure as compared with the enamel pellicle. Since
it is comprised of larger glycoproteins retaining water, it might be considered
as a hydrogel, and it appears to have a lower tenacity than the enamel pellicle.
Maturation and turnover are influenced by the delivery of salivary proteins, by
the flow of saliva and the underlying desquamating oral epithelium. Its probable
functions include lubrication and moisture retention. In general, the mucosal
pellicle can be regarded as an underestimated key player in oral physiology.
PMID- 28419913
TI - Depression and anxiety both associate with serum level of hs-CRP: A gender
stratified analysis in a population-based study.
AB - BACKGROUND: Depression and anxiety are two important mood disorders that are
frequently associated with chronic diseases such as cardiovascular diseases
(CVDs). Hyper-inflammation is related to both CVDs and psychological conditions
such as depression and anxiety. Therefore, inflammation may partially explain the
relationship between depression and cardiovascular disease. OBJECTIVE: The
objective of this study was to perform a gender-stratified examination of the
association between symptoms of depression/anxiety disorders and serum hs-CRP and
inflammation linked conditions in a large Iranian population. METHODS: Symptoms
of depression and anxiety disorders and serum hs-CRP levels were measured in 9759
participants (40% males and 60% females) aged 35-65 years, enrolled in a
population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of
depression and anxiety were evaluated with Beck Depression and Anxiety
Inventories. According to the scores of depression and anxiety, individuals were
categorized into four groups of no or minimal, low, moderate and severe
categories. RESULTS: The median serum hs-CRP concentration increased with
increasing severity of depression and anxiety disorders. Male participants with
severe depression had significantly higher levels of hs-CRP (p<0.001); however,
this relationship was less marked among women (p=0.04). Subjects with severe
anxiety also had significantly higher levels of hs-CRP (p<0.001). Moreover, women
with severe depression and anxiety had higher BMI. There was also a positive
association between current smoking habit and depression/anxiety disorders.
CONCLUSION: Depression and anxiety disorders are associated with elevated levels
of hs-CRP, particularly among men. Also, there is a significant positive
association between depression/anxiety disorders and inflammation linked
conditions such as smoking and obesity; however, in the case of obesity this
association is only present in women.
PMID- 28419914
TI - Longitudinal changes in pubertal maturation and white matter microstructure.
AB - Emerging evidence in the field of adolescent neurodevelopment suggests that
pubertal processes may contribute to known trajectories of brain maturation, and
may contribute, in part, to sex differences in related cognitive, behavioral and
mental health outcomes. The current longitudinal study examined how changes in
physical pubertal maturation (measured by the Peterson Developmental Scale)
predict changes in white matter microstructure in 18 boys and 15 girls over an
approximate 2-year follow-up period, while accounting for age. Using Tract-Based
Spatial Statistics and multi-level modeling, the results showed that physical
pubertal changes predict patterns of changes in fractional anisotropy (FA) in
white matter regions in the thalamus, precentral gyrus, superior corona radiata,
corpus callosum (genu), superior corona radiata, and superior frontal gyrus. Sex
specific changes were also seen, as changes in gonadal and adrenal development
related to increases in FA in the superior frontal gyrus and precentral gyrus in
boys, but gonadal development related to decreases in FA in the anterior corona
radiata in girls. These findings are the first to show how changes over time in
pubertal development influence white matter development. In addition, they
support a larger body of emerging research suggesting that pubertal processes
contribute to distinct changes in boys and girls across brain development.
PMID- 28419916
TI - A sensitive label-free immunosensor for detection alpha-Fetoprotein in whole
blood based on anticoagulating magnetic nanoparticles.
AB - Accurate values of tumor markers in blood play an especially important role in
the diagnosis of illness. Here, based on the combination of three techniques
include anticoagulant technology, nanotechnology and biosensing technology, a
sensitive label-free immunosensor with anti-biofouling electrode for detection
alpha-Fetoprotein (AFP) in whole blood was developed by anticoagulating magnetic
nanoparticles. The obtained products of Fe3O4-E-PL-Hep nanoparticles were
characterized by fourier transform infrared (FT-IR) spectra, transmission
electron microscopy (TEM), zeta-potential and vibrating sample magnetometry
(VSM). Moreover, the blood compatibility of anticoagulating magnetic
nanoparticles was characterized by in vitro coagulation tests, hemolysis assay
and whole blood adhesion tests. Combining the anticoagulant property of heparin
(Hep) and the good magnetism of Fe3O4, the Fe3O4-E-PL-Hep nanoparticles could
improve not only the anti-biofouling property of the electrode surface when they
contact with whole blood, but also the stability and reproducibility of the
proposed immunosensor. Thus, the prepared anticoagulating magnetic nanoparticles
modified immunosensor for the detection of AFP showed excellent electrochemical
properties with a wide concentration range from 0.1 to 100ng/mL and a low
detection limit of 0.072ng/mL. Furthermore, five blood samples were assayed using
the developed immunosensor. The results showed satisfactory accuracy with low
relative errors. It indicated that our developed immunoassay was competitive and
could be potentially used for the detection of whole blood samples directly.
PMID- 28419915
TI - Enhanced imaging of lipid rich nanoparticles embedded in methylcellulose films
for transmission electron microscopy using mixtures of heavy metals.
AB - Synthetic and naturally occurring lipid-rich nanoparticles are of wide ranging
importance in biomedicine. They include liposomes, bicelles, nanodiscs, exosomes
and virus particles. The quantitative study of these particles requires methods
for high-resolution visualization of the whole population. One powerful imaging
method is cryo-EM of vitrified samples, but this is technically demanding,
requires specialized equipment, provides low contrast and does not reveal all
particles present in a population. Another approach is classical negative stain
EM, which is more accessible but is difficult to standardize for larger lipidic
structures, which are prone to artifacts of structure collapse and contrast
variability. A third method uses embedment in methylcellulose films containing
uranyl acetate as a contrasting agent. Methylcellulose embedment has been widely
used for contrasting and supporting cryosections but only sporadically for
visualizing lipid rich vesicular structures such as endosomes and exosomes. Here
we present a simple methylcellulose-based method for routine and comprehensive
visualization of synthetic lipid rich nanoparticles preparations, such as
liposomes, bicelles and nanodiscs. It combines a novel double-staining mixture of
uranyl acetate (UA) and tungsten-based electron stains (namely phosphotungstic
acid (PTA) or sodium silicotungstate (STA)) with methylcellulose embedment. While
the methylcellulose supports the delicate lipid structures during drying, the
addition of PTA or STA to UA provides significant enhancement in lipid structure
display and contrast as compared to UA alone. This double staining method should
aid routine structural evaluation and quantification of lipid rich nanoparticles
structures.
PMID- 28419917
TI - The effect of social exclusion on state paranoia and explicit and implicit self
esteem in a non-clinical sample.
AB - BACKGROUND AND OBJECTIVES: The relationship between self-esteem and paranoia may
be influenced by social stress. This study aimed to replicate previous research
on the impact ofsocial exclusion on paranoia and self-esteem in a non-clinical
sample and to extend this work by examining the effect of exclusion on self
esteem at the 'implicit' level. METHODS: Non-clinical participants (N = 85) were
randomly allocated to the Inclusion or Exclusion condition of a virtual ball-toss
game ('Cyberball'). They completed self-reportmeasures of state paranoia and self
esteem, and two implicit measures of self-esteem - theImplicit Association Task
(IAT) and Implicit Relational Assessment Procedure (IRAP) -prior to and after
exposure to Cyberball. RESULTS: Social exclusion increased state paranoia. This
effect was moderated by distress associated with trait paranoia. Exclusion was
also associated with decreased self-reported self-esteem, as well as reduced
implicit self-esteem on the IAT. Changes in self-reported self-esteem were
associated with state paranoia at post-Cyberball. The IRAP indicated that
reductions in implicit self-esteem may be due to increases in 'Me-Negative' and
'Others-Positive' biases (rather than reductions in 'Me-Positive' bias).
LIMITATIONS: The current study involved a non-clinical sample and so findings
cannot be generalized to clinical paranoia. CONCLUSIONS: These findings are
consistent with previous evidence that paranoia is associated with negative self
evaluations, whereas positive self-evaluations can persist in paranoia. They also
provide support for the suggestion that investigations of self-esteem in paranoia
should extend beyond global self-esteem and might benefit from a distinction
between positive and negative components.
PMID- 28419918
TI - Internal shifting impairments in response to emotional information in dysphoric
adolescents.
AB - BACKGROUND AND OBJECTIVES: Previous studies have suggested that internal
cognitive control impairments may play an important role in the development of
depression. Despite a growing body of research in adults, the ability to shift
internal attention between mental representations in working memory has received
little attention in younger populations. This study investigated internal
shifting capacity between emotional and non-emotional information in dysphoric
and non-dysphoric adolescents. METHODS: Twenty dysphoric and 34 non-dysphoric
adolescents (10-17 years) completed an Internal Shifting Task, with pictures of
angry and neutral faces, to measure the ability to shift attention between
information held in working memory. RESULTS: Dysphoric adolescents showed
specific shifting impairments when processing emotional material relative to non
dysphoric adolescents. Valence-specific analyses revealed that shifting was
particularly impaired when shifting from negative to neutral information. By
comparison, relative to non-dysphoric adolescents, dysphoric adolescents did not
show shifting impairments when non-emotional features of the pictures had to be
processed. LIMITATIONS: The study is limited by the absence of a structured
clinical interview as dysphoria was determined dimensionally. Furthermore, a
comparison of the effects of different negative stimuli on shifting could not be
made since sad stimuli were not included in the stimulus set. CONCLUSIONS: The
results confirm the link between depressive symptoms and emotion-specific
shifting impairments in adolescents and indicate that targeting shifting ability
in response to emotional stimuli may be a promising avenue for prevention
programs. Longitudinal research is needed to replicate results and to explore the
role of internal shifting impairments in the etiology and maintenance of
depression.
PMID- 28419919
TI - Synthesis of layered titanate nanowires at low temperature and their application
in efficient removal of U(VI).
AB - Uranium(VI) has become one of the most potential contaminants due to its
productive and irreversibility impact on the surrounding environment. Titanate
nanowires (TNWs) have attracted significant attention because of its high ion
exchange ability and facile synthesis. Herein the TNWs were synthesized, and the
morphology and structure of TNWs were investigated by Fourier transformed
infrared spectroscopy, scanning electron microscope, transmission electron
microscope, X-ray diffraction and X-ray photoelectron spectroscopy in detail. The
application of TNWs in U(VI) removal was studied under various environmental
conditions using batch technique, and the results indicated that the sorption of
U(VI) on TNWs was strongly affected by pH and weakly affected by ionic strength.
The presence of PO43- and CO32- could overwhelmingly influence U(VI) interaction
with TNWs, which was mainly attributed to the formation of anionic and electro
neutral complexes. From the Langmuir model simulation, the maximum sorption
capacities were calculated to be 358, 384, and 410 mg g-1 at the temperatures of
298 K, 313 K and 328 K, respectively. The thermodynamic results revealed that the
interaction process was spontaneous and endothermic. The extraordinary ion
exchange capacity and facile synthesis under mild conditions made TNWs promising
materials for the potential application in the efficient elimination of U(VI) or
other lanthanides and actinides from aqueous solutions in the environmental
radioactive pollution cleanup.
PMID- 28419920
TI - The retention and distribution of parent, alkylated, and N/O/S-containing
polycyclic aromatic hydrocarbons on the epidermal tissue of mangrove seedlings.
AB - The polycyclic aromatic hydrocarbons (PAHs) located on the epidermal tissues
showed distinctive toxic effects to root, while the retention and distribution of
PAHs on mangrove seedlings poorly understood. Our results confirmed that the
partition coefficients (Kf) of the PAHs retained on the epidermal tissue of
mangrove roots, such as Kandelia obovata, Avicennia marina and Aegiceras
corniculatum, were much higher than the Poaceae plants roots, for example wheat
and maize (Wild et al., 2005). Moreover, to the parent and alkyl PAHs, a well
negative correlation was observed between the surface polarity of these three
species of mangrove root and the Kf values (p < 0.05). To the N/O/S containing
PAHs, these relationships were not obviously due to existing of the pi-pi, n-pi
interactions and hydrogen bonding between the N/O/S-containing PAHs and epidermal
tissues. The PAHs retained on these three species of mangrove root epidermal
tissues formed larger clusters than that of on Poaceae plants, such as wheat and
maize (Wild et al., 2005) due to the limitation of the suberization of the root
exodermis and endodermis. After exposure of 30 d, rhizo- and endophytic bacteria
degraded parts of the N/O/S-containing PAHs to medium-lifetime fluorescence
substances. To our knowledge, this is the first time to assess the retention of
PAHs on the epidermal tissue of mangrove root, which will improve our
understanding of the root uptake PAHs process.
PMID- 28419921
TI - Development of PM2.5 and NO2 models in a LUR framework incorporating satellite
remote sensing and air quality model data in Pearl River Delta region, China.
AB - High resolution pollution maps are critical to understand the exposure and health
effect of local residents to air pollution. Currently, none of the single
technologies used to measure or estimate concentrations of pollutants can provide
sufficient resolved exposure data. Land use regression (LUR) models were
developed to combine ground-based measurements, satellite remote sensing (SRS)
and air quality model (AQM), together with geographic and local source related
spatial inputs, to generate high resolution pollution maps for both PM2.5 and NO2
in Pearl River Delta (PRD), China. Four sets of LUR models (LUR without SRS or
AQM, with SRS only, with AQM only, and with both SRS and AQM), all including
local traffic emissions and land use variables, were compared to evaluate the
contribution of SRS and AQM data to the performance of LUR models in PRD region.
For NO2, the annual model with SRS estimate performed best, explaining 60.5% of
the spatial variation. For PM2.5, the annual model with traditional predictor
variables without SRS or AQM estimates showed the best performance, explaining
88.4% of the spatial variation. Pollution surfaces at 200 m*200 m resolution were
generated according to the best performed models.
PMID- 28419922
TI - Cadmium induces Ca2+ mediated, calpain-1/caspase-3-dependent apoptosis in primary
cultured rat proximal tubular cells.
AB - Calcium, as a ubiquitous second messenger, governs a large array of cellular
processes and is necessary for cell survival. More recently, it was observed that
the cytosolic Ca2+ concentration ([Ca2+]c) elevation could induce apoptosis in
primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but
the concrete mechanism is still unclear. This study was designed to investigate
the signal pathway involved in [Ca2+]c elevation-mediated apoptosis. The results
confirmed the elevation of [Ca2+]c by confocal microscopy and enhancement of the
apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were
exposed to Cd for 12h. Then we demonstrated that Cd enhanced the protein levels
of active calpain-1 and caspase-3 in rPT cells. Pretreatment with a cytosolic
Ca2+ chelator, 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid
acetoxymethyl ester (BAPTA-AM), markedly blocked the up-regulation of active
calpain-1 and caspase-3 and inhibited the apoptosis induced by Cd. Further, rPT
cells were pretreated with a cell-permeable selective calpain-1 inhibitor, 3-(4
iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and caspase-3 inhibitor, N
Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), respectively. PD150606 significantly
attenuated the up-regulation of active caspase-3 and the apoptosis induced by Cd.
As expected, inhibition of active caspase-3 by Ac-DEVD-CHO decreased the
apoptosis induced by Cd. Taken together, it could be concluded that [Ca2+]c
elevation did act as a pro-apoptotic signal in Cd-induced cytotoxicity of rPT
cells, triggered calpain-1 and caspase-3 activation in turn, and induced
apoptosis of rPT cells.
PMID- 28419923
TI - Development and applications of two colorimetric and fluorescent indicators for
Hg2+ detection.
AB - Two rhodamine-active probes RBAI (Rhodamine B-di-Aminobenzene-phenyl
Isothiocyanate) and RGAI (Rhodamine 6G-di-Aminobenzene-phenyl Isothiocyanate)
were designed, synthesized and characterized. The probes were developed as
fluorescent and colorimetric chemodosimeters in ethanol-water solution with a
broad pH span (5-10) and high selectivity toward Hg2+ but no significant response
toward other common competitive cations. The Hg2+-promoted ring opening of
spirolactam of the rhodamine moiety induced cyclic guanylation of the thiourea
moiety, which resulted in the dual chromo- and fluorogenic observation (off-on).
Cytotoxicity and bioimaging studies by L929 living cells and living mice
indicated that the probes were negligible cytotoxicity, cell permeable and
suitable for detecting Hg2+ in biological environments. Moreover, the new probes
not only displayed excellent abilities for the successful detection of Hg2+ in
L929 living cells and living mice but also able to detect Hg2+ by adsorbing on
solid surfaces and quantitative detection of Hg2+ in real water samples with good
recovery (more than 90%), indicating that they have promising prospect for
application for Hg2+ sensing in environmental and biological sciences.
PMID- 28419924
TI - Centrifugal partition chromatography in the isolation of minor ecdysteroids from
Cyanotis arachnoidea.
AB - Phytoecdysteroids are known for their various beneficial bioactivities in mammals
including a non-hormonal anabolic and adaptogenic effect. Cyanotis arachnoidea
extracts are extensively utilized worldwide as ecdysteroid-rich materials for
various purposes, e.g. food supplementation, use in agriculture and aquaculture,
etc. Preparative chromatography of ecdysteroids requires extensive use of methods
of different selectivity, and only a very limited number of papers are available
on related application of modern liquid-liquid chromatographic techniques. In
this work, a centrifugal partition chromatography (CPC) method was developed for
the isolation of two minor ecdysteroids, dacryhainansterone and calonysterone,
from a pre-purified commercial extract of Cyanotis arachnoidea. The biphasic
solvent system was optimized by HPLC, and was composed of n-hexane - ethyl
acetate - methanol - water (1:5:1:5, v/v/v/v). The isolated dacryhainansterone
and calonysterone represented 99.1% and 99.7% purity, respectively. Calonysterone
exerts a stronger effect on the protein kinase B (Akt) phosphorylation in
mammalian skeletal muscle cells than the abundant 20-hydroxyecdysone, while no
related data are available on dacryhainansterone. Despite their presence in food
supplements, neither compound has appropriately been assessed for safety and
efficacy. The reported method allows the gram scale isolation of these compounds,
opening ways to their in-depth pharmacological investigation.
PMID- 28419925
TI - Characterization and application of restricted access carbon nanotubes in online
extraction of anticonvulsant drugs from plasma samples followed by liquid
chromatography analysis.
AB - Anticonvulsant drugs are often used in the treatment of epilepsy. However, their
therapeutic monitoring is often necessary in order to obtain an appropriate dose
adjustment, due to the proximity between their therapeutic and toxic ranges. The
aim of this study was to carry out the synthesis, characterization and use of
restricted access carbon nanotubes (RACNTs) in an online method for the analyses
of phenobarbital and carbamazepine and primidone from untreated human blood
plasma by column switching liquid chromatography. Therefore, the synthesis of
RACNTs was carried out through coating commercial Carbon nanotubes with bovine
serum albumin (BSA) to subsequently use them as adsorbents in a column switching
system operating in the backflush mode. This material was evaluated through the
construction of the kinetic and isotherm curves. The experimental data for the
interaction of primidone with RACNTs were adequately adjusted to the
chemisorption and Sips models for the kinetic and adsorption studies,
respectively. The analytical curves ranged from 2.0 to 40.0mgL-1, with
correlation coefficients higher than 0.99, for all the analytes. The LODs of 0.1,
0.1 and 0.01MUgmL-1 were defined for PHB, PRM and CBZ, respectively. The relative
standard deviation values ranged from 1.0% to 8.4% for the intra assay precision
and from 2.7% to 7.6% for inter assay precision. The relative error values ranged
from -13.4% to 7.7% for the intra assay accuracy and from -8.6% to 2.5% for the
inter assay accuracy. The method was adequately used in the therapeutic
monitoring of anticonvulsant drugs in human plasma samples.
PMID- 28419926
TI - Stability and activity of immobilized trypsin on carboxymethyl chitosan
functionalized magnetic nanoparticles cross-linked with carbodiimide and
glutaraldehyde.
AB - Enzyme cross-linkers, such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
(EDC) and glutaraldehyde (GA), have been used to improve the stability of
immobilized enzymes. We have developed a relatively stable and high-activity
immobilized trypsin through EDC and GA cross-linking. Carboxymethyl chitosan (CM
CTS)-functionalized magnetic nanoparticles (Fe3O4@CM-CTS) were prepared, and
characterized by Fourier transform infrared spectroscopy (FTIR),
thermogravimetric analysis, X-ray diffraction, and transmission electron
microscopy. The CM-CTS loading of Fe3O4 @CM-CTS was 8.701%, and the CM-CTS
coating did not cause any significant changes in the crystal structure of Fe3O4.
The Fe3O4@CM-CTS nanoparticles exhibited superparamagnetic properties. Trypsin
was successfully immobilized on Fe3O4@CM-CTS via EDC and GA cross-linking
(Fe3O4@CM-CTS-EDC-TRY and Fe3O4@CM-CTS-GA-TRY, respectively). Trypsin
immobilization was verified by FTIR and enzyme assays. Changes in the secondary
structures of the immobilized trypsin were present in both Fe3O4@CM-CTS-EDC-TRY
and Fe3O4@CM-CTS-GA-TRY. However, kinetic studies demonstrated that the
immobilized trypsin retained efficient biocatalytic activity. Fe3O4@CM-CTS-EDC
TRY and Fe3O4@CM-CTS-GA-TRY both showed maximum catalytic activity at pH 8.4 and
45 degrees C, and retained 71% and 88.5%, respectively, of their initial
activities after 6 usage cycles, and 80% and 88% of their initial activities
after being stored for 14 d at 4 degrees C. The Fe3O4@CM-CTS-GA-TRY showed higher
activity and conformational stability than Fe3O4@CM-CTS-EDC-TRY, which indicates
that GA is effective for the immobilization of trypsin on Fe3O4@CM-CTS.
PMID- 28419927
TI - Synthesis and evaluation of anti-plasmodial and cytotoxic activities of
epoxyazadiradione derivatives.
AB - Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti
plasmodial activity against CQ-resistant and CQ-sensitive strains of the most
virulent human malaria parasite P. falciparum. A series of analogues were
synthesized by modification of the key structural moieties of this high yield
natural product. Out of the library of all compounds tested, compounds 3c and 3g
have showed modest anti-plasmodial activity against CQ-sensitive (IC50 2.8 +/-
0.29 MUM and 1.5 +/- 0.01 MUM) and CQ-resistant strains (IC50 1.3 +/- 1.08 MUM
and 1.2 +/- 0.14), while compounds 3k, 3l and 3m showed modest activity against
CQ-sensitive strain of P. falciparum with IC50 values of 2.3 +/- 0.4 MUM, 2.9 +/-
0.1 MUM and 1.7 +/- 0.06 MUM, respectively. Additionally, cytotoxic properties of
these derivatives against SIHA, PANC 1, MDA-MB-231, and IMR-3 cancer cell lines
were also studied and the results indicated that low cytotoxic potentials of all
the derivatives which indicating the high selectivity index of the compounds.
PMID- 28419928
TI - Design, synthesis and biological evaluation of 3-substituted-2-oxindole hybrid
derivatives as novel anticancer agents.
AB - The 2-oxindole nucleus is the central core to develop new anticancer agents and
its substitution at the 3-position can effect antitumor activity. Utilizing a
pharmacophore hybridization approach, a novel series of antiproliferative agents
was obtained by the modification of the structure of 3-substituted-2-oxindole
pharmacophore by the attachment of the alpha-bromoacryloyl moiety, acting as a
Michael acceptor, at the 5-position of 2-oxindole framework. The impact of the
substituent at the 3-position of 2-oxindole core on the potency and selectivity
against a panel of seven different cancer cell lines was examined. We found that
these hybrid molecules displayed potent antiproliferative activity against a
panel of four cancer cell lines, with one-to double digit nanomolar 50%
inhibitory concentrations (IC50). A distinctive selective antiproliferative
activity was obtained towards CCRF-CEM and RS4; 11 leukemic cell lines. In order
to study the possible mechanism of action, we observed that the two most active
compounds namely 3(E) and 6(Z) strongly induce apoptosis that follow the
mitochondrial pathway. Interestingly a decrease of intracellular reduced
glutathione content (GSH) and reactive oxygen species (ROS) production was
detected in treated cells compared with controls suggesting that these effects
may be involved in their mechanism of action.
PMID- 28419929
TI - (R)- and (S)-18F-labeled 2-arylbenzofurans with improved pharmacokinetics as beta
amyloid imaging probes.
AB - A new class of optical isomers of 2-arylbenzofuran derivatives were synthesized
and evaluated as potential beta-amyloid plaques imaging agents. Both
lipophilicity and signal-to-noise ratio were significantly improved by adding a
chiral hydroxyl group to 1-fluoro-3-(oxidanyl)propan-2-ol side chain. These
derivatives displayed moderate to high binding affinity towards Abeta1-42
aggregates. Four tracers possessing potent binding affinity (Ki < 30 nM) were
chosen for further investigation. In in vitro autoradiography studies, the four
selected probes showed effective binding to Abeta plaques in Tg mouse and AD
human brain tissue after labeled by 18F. The purified enantiomers displayed
apparent discrepancy in biodistribution experiments in normal mice, for (S)
enantiomers provided rather faster clearance than (R)-enantiomers. All in all,
(S)-[18F]17 (Ki = 14.6 nM) with excellent pharmacokinetics (brain2 min = 8.60%
ID/g, brain2 min/brain60 min = 14.1) deserves further evaluation.
PMID- 28419930
TI - Design, synthesis and anticancer potential of NSC-319745 hydroxamic acid
derivatives as DNMT and HDAC inhibitors.
AB - DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important
epigenetic targets during anticancer drug development. Recent study indicates
that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain
cancers, therefore, development of molecules targeting both DNMT and HDAC is of
therapeutic advantage against these cancers. Based on the structure of DNMT
inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a
series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized
as DNMT and HDAC multifunctional inhibitors. Most compounds displayed potential
DNMT inhibitory potency and potent HDAC inhibitory activity, especially compound
15a showed much better DNMT1 inhibitory potency than NSC-319745, and inhibited
HDAC1, HDAC6 with IC50 values of 57, 17 nM, respectively. Furthermore, the
synthesized compounds exhibited significant cytotoxicity against human cancer
cells K562 and U937. Further mechanistic studies demonstrated that 15a treatment
in U937 increased histones H3K9 and H4K8 acetylation, prompted P16 CpG islands
demethylation and upregulated P16 expression, regulated apoptosis-related protein
expression on the cellular level and induced remarkable U937 apoptosis. Moreover,
genotoxicity of representative compounds was evaluated. In summary, our study
provided a practical drug design strategy targeting multiple enzymes, and 15a
represents a novel and promising lead compound for the development of novel
epigenetic inhibitors as antitumor agents.
PMID- 28419931
TI - Applying the design-build-test paradigm in microbiome engineering.
AB - The recently discovered roles of human microbiome in health and diseases have
inspired research efforts across many disciplines to engineer microbiome for
health benefits. In this review, we highlight recent progress in human microbiome
research and how modifications to the microbiome could result in implications to
human health. Furthermore, we discuss the application of a 'design-build-test'
framework to expedite microbiome engineering efforts by reviewing current
literature on three key aspects: design principles to engineer the human
microbiome, methods to engineer microbiome with desired functions, and analytical
techniques to examine complex microbiome samples.
PMID- 28419932
TI - Competitive removal of heavy metal ions from squid oil under isothermal condition
by CR11 chelate ion exchanger.
AB - Heavy metal ions (HMIs) are serious threats to the environment. Sub-critical
water treatment was used to mimic contamination of squid oil in aqueous, metal
soap and oil phases. Isothermal adsorption of HMIs (Cu2+, Pb2+, Cd2+ and Zn2+)
was studied from aqueous phase to oil phase (493, 523, 548, and 573K) for
solutions with different initial concentration of HMIs was studied. Decomposition
of glycerides into fatty acids was favored at high subcritical temperatures, with
metal-soap phase showing the highest chelation ability toward Cu2+ (96%, isotherm
573K). The removal-ability of HMIs from contaminated oil was performed by CR11
chelate ion exchanger, showing facilitated removal from metal-soap and oil phases
at low temperatures compared to general-purpose PEI-chitosan bead and PEI
chitosan fiber sorbents. The chelation behavior of Pb2+ and Cd2+ was the same in
the OIL, with maximum values of 5.7*10-3 (mol/l) and 5.0*10-3 (mol/l) at 573K,
respectively. By contrast, concentration of Zn2+ ion showed a slight increase
with increasing temperature due to electrostatic forces between Zn2+ and active
sites of glycerides in oil phase. For oil solution, the selectivity of adsorption
for CR11, especially for Zn2+, was at least five-fold larger compared to PEI
chitosan bead and PEI-chitosan fiber adsorbents.
PMID- 28419933
TI - Planar polarized contractile actomyosin networks in dynamic tissue morphogenesis.
AB - The complex shapes of animal bodies are constructed through a sequence of simple
physical interactions of constituent cells. Mechanical forces generated by
cellular activities, such as division, death, shape change and rearrangement,
drive tissue morphogenesis. By confining assembly or disassembly of actomyosin
networks within the three-dimensional space of the cell, cells can localize
forces to induce tissue deformation. Tissue-scale morphogenesis emerges from a
collective behavior of cells that coordinates the force generation in space and
time. Thus, the molecular mechanisms that govern the temporal and spatial
regulation of forces in individual cells are elemental to organogenesis, and the
tissue-scale coordination of forces generated by individual cells is key to
determining the final shape of organs.
PMID- 28419934
TI - Genome research elucidating environmental adaptation: Dark-fly project as a case
study.
AB - Organisms have the capacity to adapt to diverse environments, and environmental
adaptation is a substantial driving force of evolution. Recent progress of genome
science has addressed the genetic mechanisms underlying environmental adaptation.
Whole genome sequencing has identified adaptive genes selected under particular
environments. Genome editing technology enables us to directly test the role(s)
of a gene in environmental adaptation. Genome science has also shed light on a
unique organism, Dark-fly, which has been reared long-term in the dark. We
determined the whole genome sequence of Dark-fly and reenacted environmental
selections of the Dark-fly genome to identify the genes related to dark
adaptation. Here I will give an overview of current progress in genome science
and summarize our study using Dark-fly, as a case study for environmental
adaptation.
PMID- 28419935
TI - Identification of a host cell protein impurity in therapeutic protein, P1.
AB - Residual host cell proteins (HCPs) are process-related impurities present in
biotherapeutics that can pose safety health risks to patients. An adequate
control of HCP levels in the final product, and demonstration of HCP clearance
throughout a product manufacturing process is critical for all biotherapeutic
products. Developing effective downstream purification processes can be
challenging as HCPs and product proteins may possess an affinity for each other
or have similar physicochemical properties, resulting in co-purification. In the
current study, we identified the presence of CHO-catalase subunit protein as an
impurity present in purified P1 protein. This previously unreported HCP impurity,
was detected in P1 protein generated in Chinese hamster ovary (CHO) cells.
Purified drug substance samples contained elevated CHO HCP levels when measured
using a commercial anti-CHO HCP Enzyme-Linked Immunosorbent Assay (ELISA) kit.
This finding, prompted further characterization of the HCP profile using 1D and
2D gels/ western blots using an anti-human IgG antibody as well as a commercial
anti-CHO HCP antibody (Cygnus 813) for the detection of host cell proteins. The
CHO-catalase protein has been characterized using a combination approach of one
dimensional (1D) and two-dimensional (2D) gels and western blotting techniques,
and the identity confirmed using liquid chromatography-mass spectrometry (LC
MS/MS) analysis. Western blot analyses using the anti-CHO HCP antibody detected a
potential HCP band at ~60 kDa and a pI of ~8 in the purified P1 sample. The 60
kDa HCP band was excised from 1D SDS-PAGE gels and LC-MS/MS analysis identified
it to be CHO-catalase subunit. The identity of catalase monomer was further
confirmed by western blot analysis using a specific anti-catalase antibody.
PMID- 28419936
TI - Simultaneous separation and determination of four uncaria alkaloids by capillary
electrophoresis using dual cyclodextrin system.
AB - The purpose of this study was to develop a simple, quick and precise capillary
zone electrophoresis method (CZE) for the separation and determination of uncaria
alkaloids using dual cyclodextrins as additives for the separation. The four
analytes were baseline separated within 15min at the applied voltage of 15kV with
a running buffer (pH 5.7) consisting of 40.0mM phosphate buffer, 161.7mM 2
hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and 2.21mM mono-(6-ethylenediamine-6
deoxy)-beta-cyclodextrin (ED-beta-CD). Under the optimum conditions, a good
linearity was achieved with correlation coefficients from 0.9989 to 0.9992. The
detection limits and the quantitation limits ranged from 0.63 to 0.98MUg/mL and
from 2.08 to 3.28MUg/mL, respectively. Excellent accuracy and precision were
obtained. Recoveries of the analytes varied from 97.1 to 103.2%. This method was
suitable for the quantitative determination of these alkaloids in the stem with
hook of Uncaria rhynchophylla and the formulations of Uncaria rhynchophylla.
PMID- 28419937
TI - Validation and application of an ultrahigh-performance liquid chromatographic
Orbitrap mass spectrometric method for the simultaneous detection and
quantification of volatile and non-volatile organic acids in human faecal
samples.
AB - A simple and selective ultrahigh-performance liquid chromatographic-Orbitrap mass
spectrometric (UHPLC-HR-MS) method was developed and validated for the
simultaneous detection and quantification of short-chain fatty acids (SCFAs) such
as acetic, propionic, butyric, isobutyric, valeric, isovaleric, 2-methyl-butyric
(IS) and lactic, pyruvic and succinic acid in human faecal samples. A simple
extraction procedure with 0.001% formic acid in water was performed on 40
samples. The extracts were centrifuged and analyzed by UHPLC-HR-MS on a sub-2MUm
column using gradient elution; meanwhile, the same samples were analyzed by GC
FID and HPLC-UV as reference methods The UHPLC-HR-MS method showed a recovery of
83-105%, a repeatability of 2.2-8.3% and an intermediate precision of 2.9-9.4%.
The LOD and LLOQ were in the range of 0.04-0.23 and 0.2-0.5MUg/ml, respectively.
Regarding the SCFAs, statistical analysis showed a good correlation between the
data obtained by UHPLC-HR-MS and those provided by GC-FID (p>0.05). On the
contrary, the LC-UV data were not in agreement with those obtained by UHPLC-HR-MS
determination (p<0.05). To the best of our knowledge, this is the first method
available for the simultaneous extraction and quantification of SCFAs, lactic,
pyruvic and succinic in faecal samples by UHPLC-HR-MS.
PMID- 28419939
TI - The 5-HT4 receptor agonist prucalopride does not facilitate cholinergic
neurotransmission in circular and longitudinal smooth muscle preparations of
equine mid-jejunum.
AB - BACKGROUND: Postoperative ileus (POI) remains an important cause of death in
horses. The recently developed selective 5-HT4 receptor agonists such as
prucalopride target 5-HT4 receptors on myenteric cholinergic neurons to enhance
acetylcholine release and GI motility. No clearcut in vitro evaluation whether
highly selective 5-HT4 receptor agonists enhance submaximal cholinergic
neurotransmission towards the muscle layer has been performed in horses.
OBJECTIVES: To identify functional 5-HT4 receptors in equine jejunum. STUDY
DESIGN: In vitro experimental study. METHODS: Circular and longitudinal smooth
muscle strips (mid-jejunum) were mounted in organ baths between 2 platinum
electrodes allowing electrical field stimulation (EFS). To delineate the
conditions to obtain purely cholinergic responses, voltage-response curves were
studied. To investigate the influence of prucalopride and 5-HT, submaximal
cholinergic contractions at a single voltage were induced. RESULTS: In circular
and longitudinal strips, EFS induced voltage-dependent neurogenic on-contractions
when the bathing medium contained a NO-synthesis inhibitor and apamin to prevent
inhibitory responses to NO and ATP. Contractions at a voltage inducing 50% of
maximal amplitude were cholinergic, as they were blocked by atropine. These
contractions were not influenced by prucalopride (up to 3MUM), even in the
presence of the phosphodiesterase inhibitor isobutyl-methyl-xanthine to inhibit
breakdown of the second messenger of 5-HT4 receptors, cAMP. Also the full 5-HT4
receptor agonist 5-HT did not influence the EFS-induced submaximal cholinergic
contractions. Moreover, prucalopride did not influence muscle tone continuously
enhanced with KCl. CONCLUSIONS: There are no functional 5-HT4 receptors on
myenteric cholinergic neurons nor muscular 5-HT4 receptors in equine jejunum.
PMID- 28419938
TI - Direct-acting antivirals: the endgame for hepatitis C?
AB - Directly-acting antivirals (DAA) have finally allowed all patients to be
potentially cured from chronic hepatitis C (HCV) infection. All-oral, Interferon
(IFN)-free regimens are based upon the combination of molecules targeting
different sites of the HCV replication process. Three classes of DAA exist:
protease inhibitors (anti-NS3/4A), RNA-dependent polymerase inhibitors (anti
NS5B) and anti-NS5A inhibitors, which are characterized by different antiviral
potency and barrier to resistance and therefore are usually combined in different
treatment schedules. Treatment regimens are still largely dependent on HCV
genotype and stage of liver disease, with duration ranging between 12 weeks and
24 weeks, while overall treatment efficacy has climbed to nearly 95% in most
patient groups, including historically difficult-to-treat categories (HCV
genotype 1, advanced liver disease). The elimination of IFN has allowed safe and
efficacious treatment of patients formerly contraindicated to antiviral therapy,
such as decompensated cirrhosis and solid organ transplant recipients.
Availability of potent and safe antiviral drugs combined with improvement of
worldwide access to treatment could finally lead to HCV elimination in the next
decades.
PMID- 28419940
TI - Cholesterol concentrations in lipoprotein fractions separated by anion-exchange
high-performance liquid chromatography in healthy dogs and dogs with
hypercholesterolemia.
AB - Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for
measurement of cholesterol can be used to separate serum lipoproteins (high
density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density
lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX
HPLC has not been applied in veterinary practice. We had three objectives: (i)
the validation of AEX-HPLC methods including the correlation of serum cholesterol
concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation
HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was
investigated; (ii) the reference intervals of lipoprotein fractions measured by
AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions
from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23)
were compared. Analytic reproducibility and precision of AEX-HPLC were
acceptable. Positive correlation between serum concentrations of total
cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL
Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for
AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia.
Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol,
HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16
3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant
difference in lipoprotein profiles between healthy and dogs with
hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate
lipoprotein profiles in dogs and could be a new useful indicator of
hyperlipidemia in dogs.
PMID- 28419941
TI - PAMAM (generation 4) incorporated gelatin 3D matrix as an improved dermal
substitute for skin tissue engineering.
AB - The study explored the prospects of PAMAM (generation 4) applicability in gelatin
based scaffolds for skin tissue engineering. The effect of PAMAM on physico
chemical and biological characteristics of gelatin scaffolds was evaluated.
Gelatin scaffolds (with/without PAMAM) were prepared by lyophilization,
chemically crosslinked by glutaraldehyde and characterized for their morphology
(pore size), chemical features (bond nature), water adsorption, biodegradation
and biological compatibility. The study demonstrated that addition of PAMAM did
not significantly alter the pore size distribution or porosity of the scaffolds.
However, water adsorption potential and collagenase mediated degradation
significantly enhanced over period of the study. Both the scaffolds (with/without
PAMAM) were highly biocompatible and hemocompatible. PAMAM (G4) blended scaffolds
showed relatively higher cellular adhesion and proliferation of both
keratinocytes and fibroblasts with an improved gene expression profile of native
collagen type I of fibroblasts. Moreover, expression of angiogenesis inducing
genes, HIF1alpha and VEGF were also higher in PAMAM blended gelatin matrix. Also,
PAMAM incorporated gelatin matrix showed a slower rate of drug release which
confirms its suitability for therapeutic delivery during wound healing. These
results clearly suggest that blending PAMAM (G4) into the matrix could provide an
additional support to scaffold assisted wound healing.
PMID- 28419942
TI - Nucleotide-directed syntheses of gold nanohybrid systems with structure-dependent
optical features: Selective fluorescence sensing of Fe3+ ions.
AB - This study demonstrates a one-step synthesis for the preparation of both
adenosine monophosphate (AMP)-stabilized colloidal gold nanoparticles (AMP-Au
NPs) and fluorescent gold nanoclusters (AMP-Au NCs). The dominant role of
AMP:AuCl4- molar ratios in the formation of diverse nanosized Au products was
proved. The size, the structure and the unique structure-dependent optical
properties of the NPs and NCs were determined based on the results of numerous
spectroscopic (UV-vis, fluorescence, infrared, x-ray photoelectron), high
resolution electron microscopy (HRTEM) and dynamic light scattering (DLS)
techniques. Stabile AMP-Au NPs with diameter of ca. 11nm and ultra-small AMP-Au
NCs having blue fluorescence (lambdaem=480nm) were identified. In addition, the
AMP-Au NCs have been utilized to develop a selective sensor for the detection of
Fe3+ ions in aqueous medium based on fluorescence quenching. Several essential
metal ions and anions have been tested but our results clearly supported that
dominant quenching was observed only for Fe3+ ions. Based on the determined limit
of detection (LOD=2.0MUM) our system is capable of detecting Fe3+ ions in
drinking water. The Stern-Volmer constants (KSV) and various thermodynamic
parameters (DeltaG, DeltaH degrees , DeltaS degrees , DeltaCp) of the quenching
process have also been determined by the Stern-Volmer fitting of the fluorescence
data in order to better understand the quenching mechanism.
PMID- 28419943
TI - Interconnectivity of macroporous molecularly imprinted polymers fabricated by
hydroxyapatite-stabilized Pickering high internal phase emulsions-hydrogels for
the selective recognition of protein.
AB - Hydroxyapatite hybridized molecularly imprinted polydopamine polymers with
selective recognition of bovine hemoglobin (BHb) were successfully prepared via
Pickering oil-in-water high internal phase emulsions-hydrogels and molecularly
imprinting technique. The emulsions were stabilized by hydroxyapatite of which
the wettability was modified by 3-methacryloxypropyltrimethoxysilane. The
materials were characterized by SEM, IR and TGA. The results showed that the BHb
imprinted polymers based on Pickering hydrogels (Hydro-MIPs) possess macropores
ranging from 20MUm to 50MUm, and their large numbers of amino groups and hydroxyl
groups result in a favorable adsorption capacity for BHb. The maximum adsorption
capacity of Hydro-MIPs for BHb was 438mg/g, 3.27 times more than that of the non
imprinted polymers (Hydro-NIPs). The results indicated that Hydro-MIPs possessing
well-defined hierarchical porous structures exhibited outstanding recognition
behavior towards the target protein molecules. This work provided a promising
alternative method for the fabrication of polymer materials with tunable and
interconnected pores structures for the separation and purification of protein in
vitro.
PMID- 28419944
TI - Electrochemical synthesis of three-dimensional porous reduced graphene oxide
film: Preparation and in vitro osteogenic activity evaluation.
AB - In this study, three-dimensional reduced graphene oxide (3D-rGO) porous films
were fabricated using a two-step electrochemical method, including an
electrochemical deposition process for the self-assembly of GO and an
electrochemical bubbling-based transfer. The morphology, physical properties, and
phase composition of the 3D-rGO films were characterized, and the cellular
bioactivities were evaluated using pre-osteoblasts (MC3T3-E1 cells). The
attachment, proliferation and differentiation of the MC3T3-E1 cells on the 3D-rGO
films was analyzed by scanning electron microscopy (SEM), Cell Counting Kit-8
(CCK-8) assays and live/dead cell staining, and alkaline phosphatase (ALP)
activity assays, respectively. The expression of osteogenic-related genes in
MC3T3-E1 cells was evaluated by reverse transcription-polymerase chain reaction
(RT-PCR). The results showed that the 3D-rGO films supported cell viability and
proliferation, as well as significantly enhanced ALP activity and osteogenic
related genes (ALP, OPN, Runx2) expressions. Our findings indicate the promising
potential of the 3D-rGO porous films for bone tissue engineering.
PMID- 28419945
TI - Interaction of alpha-synuclein with Rhus typhina tannin - Implication for
Parkinson's disease.
AB - The etiology of Parkinson's disease (PD) relates to alpha-synuclein, a small
protein with the ability to aggregate and form Lewy bodies. One of its prevention
strategies is inhibition of alpha-synuclein oligomerization. We have investigated
the interaction of alpha-synuclein and human serum albumin with 3,6-bis-O-di-O
galloyl-1,2,4-tri-O-galloyl-beta-d-glucose (a tannin isolated from the plant Rhus
typhina). Using fluorescence spectroscopy method we found that this tannin
interacts strongly with alpha-synuclein forming complexes. Circular dichroism
analysis showed a time-dependent inhibition of alpha-synuclein aggregation in the
presence of the tannin. On the other hand, 3,6-bis-O-di-O-galloyl-1,2,4-tri-O
galloyl-beta-d-glucose had a much stronger interaction with human serum albumin
than alpha-synuclein. The calculated binding constant for tannin-protein
interaction was considerably higher for albumin than alpha-synuclein. This tannin
interacted with albumin through a "sphere of action" mechanism. The results lead
to the conclusion that 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-beta-d-glucose
is a potent preventive compound against Parkinson's disease. However, this tannin
interacts very strongly with human serum albumin, significantly reducing the
bioavailability of this compound.
PMID- 28419946
TI - Water-immiscible bioinert coatings and film formation from aqueous dispersions of
poly(2-methoxyethyl acrylate) microspheres.
AB - Poly(2-methoxyethyl acrylate) (pMEA) microspheres are prepared through facile
free-radical polymerization in water without additives and impurities, such as
surfactants, other polymers, and organic solvents, which are usually used to
synthesize pMEA chains. Clean and pure (non-factionalized and non-cross-linking)
pMEA microspheres exhibit plasma-protein adsorption resistances on their surface
regardless of their charged state. They are characterized in terms of the
adsorbed amounts of proteins at pH 7. In addition, these soft and deformable pMEA
microspheres are suitable for forming substrates coated with pMEA microspheres
and free-standing films by injecting pMEA dispersion and evaporating the aqueous
medium through fusion between the pMEA chains at the surface without the
precoating agent and cross-linker. These pMEA coatings have been used till now in
artificial heart/lung fabrication and metal products manufacturing by casting
organic solvents such as 1,4-dioxane, toluene, and methanol and dissolving pMEA
chains prepared using conventional solution polymerization. In this study,
bioinert coatings and adhesive and transferable films are easily obtained due to
the rubber-like properties of the pMEA microspheres and stable in mild and
biocompatible conditions even when these impurities are not used completely,
allowing us to provide a guideline for potential pMEA bioapplications such as
coatings, films, barriers, and implant devices.
PMID- 28419947
TI - Efficacy and safety of eslicarbazepine-acetate in elderly patients with focal
epilepsy: Case series.
AB - PURPOSE: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug
licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety
of ESL have been established in real-life setting. However, data about outcomes
in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL
in elderly patients. METHOD: This was a retrospective survey that included
patients >65years with focal seizures who started ESL between January 2010 and
July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to
real-life practice. Efficacy and safety were evaluated over 1year. These patients
were included within the bigger study ESLIBASE. RESULTS: We included 29 patients,
most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20
years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose
was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were
seizure-free. At 12 months, 16 patients (55.2%) had >=1 adverse effect (AE), that
led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most
common AEs. The tolerability profile improved in 4/5 patients who switched from
carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. CONCLUSIONS: ESL
was well-tolerated and effective in elderly patients in a real-life setting over
1year, with a dose around 800mg/day. AE effects improved in most of who switched
from CBZ or OXC to ESL.
PMID- 28419948
TI - Genetic generalized epilepsy in three siblings with 8q21.13-q22.2 duplication.
AB - PURPOSE: Duplication of chromosome region 8q21-q22 is a rare copy number variant
that has been previously reported in a limited number of patients. Although some
of these patients had seizures, their electroclinical syndrome has not been
described in detail. The aim of this study was to provide further insight into
the specific epilepsy syndrome associated with 8q21.13-q22.2 duplication. METHOD:
We describe 3 siblings with trisomy of 8q21.13-q22.2 who exhibited intellectual
disability, facial dysmorphism and seizures. RESULTS: All of the patients
responded satisfactorily to antiepileptic medication. The EEG showed typical 3-Hz
generalized spike-and-wave interictal discharges. Microarray analyses revealed
duplication of 8q21.13-q22.2, encompassing 10 OMIM morbid map genes. The analysis
demonstrated that the parental origin of the additional copy of 8q22.13-q22.2 was
maternal, translocated to chromosome 4p. CONCLUSION: Our report supports that
duplication of 8q21.13-q22.2 is associated with genetic generalized epilepsy with
early onset absence and generalized tonic clonic seizures, in addition to the
previously reported features of intellectual disability and dysmorphism.
PMID- 28419949
TI - Characteristics of seizure-induced signal changes on MRI in patients with first
seizures.
AB - PURPOSE: The aim of this study was to investigate the predictive factors and
identify the characteristics of the seizure-induced signal changes on MRI (SCM)
in patients with first seizures. METHODS: We conducted a retrospective study of
patients with first seizures from March 2010 to August 2014. The inclusion
criteria for this study were patients with 1) first seizures, and 2) MRI and EEG
performed within 24h of the first seizures. The definition of SCM was hyper
intensities in the brain not applying to cerebral arterial territories.
Multivariate logistic regression was performed with or without SCM as a dependent
variable. RESULTS: Of 431 patients with seizures visiting the ER, 69 patients met
the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform
discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently
significant variable predicting the presence of SCM in patients with first
seizures. In addition, the topography of SCM was as follows; i) ipsilateral
hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11),
iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus
(1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI
exhibited unilateral cortical hyperperfusion with ipsilateral thalamic
involvement reflecting unrestricted vascular territories. CONCLUSION: There is an
association between epileptiform discharges and SCM. Additionally, the
involvement of the unilateral cortex and ipsilateral thalamus in SCM and its
hyperperfusion state could be helpful in differentiating the consequences of
epileptic seizures from other pathologies.
PMID- 28419950
TI - River bottom sediment from the Vistula as matrix of candidate for a new reference
material.
AB - Bottom sediments are very important in aquatic ecosystems. The sediments
accumulate heavy metals and compounds belonging to the group of persistent
organic pollutants. The accelerated solvent extraction (ASE) was used for
extraction of 16 compounds from PAH group from bottom sediment of Vistula. For
the matrix of candidate of a new reference material, moisture content, particle
size, loss on ignition, pH, and total organic carbon were determined. A gas
chromatograph with a selective mass detector (GC/MS) was used for the final
analysis. The obtained recoveries were from 86% (SD=6.9) for anthracene to 119%
(SD=5.4) for dibenzo(ah)anthracene. For the candidate for a new reference
material, homogeneity and analytes content were determined using a validated
method. The results are a very important part of the development and
certification of a new reference materials.
PMID- 28419951
TI - Can fractal methods applied to video tracking detect the effects of deltamethrin
pesticide or mercury on the locomotion behavior of shrimps?
AB - Shrimps can accumulate environmental toxicants and suffer behavioral changes.
However, methods to quantitatively detect changes in the behavior of these
shrimps are still needed. The present study aims to verify whether mathematical
and fractal methods applied to video tracking can adequately describe changes in
the locomotion behavior of shrimps exposed to low concentrations of toxic
chemicals, such as 0.15ugL-1 deltamethrin pesticide or 10ugL-1 mercuric chloride.
Results showed no change after 1min, 4, 24, and 48h of treatment. However, after
72 and 96h of treatment, both the linear methods describing the track length,
mean speed, mean distance from the current to the previous track point, as well
as the non-linear methods of fractal dimension (box counting or information
entropy) and multifractal analysis were able to detect changes in the locomotion
behavior of shrimps exposed to deltamethrin. Analysis of angular parameters of
the track points vectors and lacunarity were not sensitive to those changes. None
of the methods showed adverse effects to mercury exposure. These mathematical and
fractal methods applicable to software represent low cost useful tools in the
toxicological analyses of shrimps for quality of food, water and biomonitoring of
ecosystems.
PMID- 28419952
TI - Antimony and arsenic exhibit contrasting spatial distributions in the sediment
and vegetation of a contaminated wetland.
AB - Antimony is a priority environmental contaminant that is relatively poorly
studied compared to other trace metal(loid)s. In particular, the behaviour of
antimony in wetland sediments, where anaerobic conditions often dominate, has
received considerably less attention compared to well-drained terrestrial soil
environments. Here we report the results of a spatial assessment of antimony in
the sediments and vegetation of a freshwater wetland exposed to stibnite tailings
for the past forty years. The concentration of antimony in the sediment decreased
rapidly with distance from the tailings deposit, from a maximum of ~22,000 mg kg
1 to ~1000 mg kg-1 at a distance of ~150 m. In contrast, arsenic was distributed
more evenly across the wetland, indicating that it was more mobile under the
prevailing hypoxic/anoxic conditions. Less clear trends were observed in the
tissues of wetland plants, with the concentrations of antimony in waterlilies
(2.5-195 mg kg-1) showing no clear trends with distance from the tailings
deposit, and no correlation with sediment concentrations. Sedges and Melaleuca
sp. trees had lower antimony concentrations (<25 mg kg-1 and 5 mg kg-1,
respectively) compared to waterlilies, but showed a non-significant trend of
higher concentrations closer to the tailings. For all vegetation types sampled,
antimony concentrations were consistently lower than arsenic concentrations
(Sb:As = 0.27-0.31), despite higher concentrations of antimony in the sediment.
Overall, the results of this study highlight clear differences in the behaviour
of antimony and arsenic in freshwater wetlands, which should be considered during
the management and remediation of such sites.
PMID- 28419953
TI - Exploiting extracellular polymeric substances (EPS) controlling strategies for
performance enhancement of biological wastewater treatments: An overview.
AB - Extracellular polymeric substances (EPS) are present both outside of the cells
and in the interior of microbial aggregates, and account for a main component in
microbial aggregates. EPS can influence the properties and functions of microbial
aggregates in biological wastewater treatment systems, and specifically EPS are
involved in biofilm formation and stability, sludge behaviors as well as
sequencing batch reactors (SBRs) granulation whereas they are also responsible
for membrane fouling in membrane bioreactors (MBRs). EPS exhibit dual roles in
biological wastewater treatments, and hence the control of available EPS can be
expected to lead to changes in microbial aggregate properties, thereby improving
system performance. In this review, current updated knowledge with regard to EPS
basics including their formation mechanisms, important properties, key component
functions as well as sub-fraction differentiation is given. EPS roles in
biological wastewater treatments are also briefly summarized. Special emphasis is
laid on EPS controlling strategies which would have the great potential in
promoting microbial aggregates performance and in alleviating membrane fouling,
including limitation strategies (inhibition of quorum sensing (QS) systems,
regulation of environmental conditions, enzymatic degradation of key components,
energy uncoupling etc.) and elevation strategies (enhancement of QS systems,
addition of exogenous agents etc.). Those strategies have been confirmed to be
feasible and promising to enhance system performance, and they would be a
research niche that deserves further study.
PMID- 28419954
TI - Osmoregulatory responses to cadmium in reference and historically metal
contaminated Gammarus fossarum (Crustacea, Amphipoda) populations.
AB - In order to better understand the variable sensitivities of crustaceans to
metals, we investigated the impact of cadmium exposure in 3 populations of
Gammarus fossarum from different rivers of France. The first population lives in
a Cd-contaminated river from a geochemical background, while the others inhabit
Cd-free sites. Osmoregulation, a relevant biomarker to evaluate crustacean health
following metal contamination, was used as a proxy to evaluate the intra- and
inter-populationnal sensitivities to Cd. Specimens from each population were
experimentally exposed to 9 MUg Cd2+/L Cd for 7 days and hemolymph osmolality
(HO) was then individually measured. In exposed populations, high inter
individual variations in HO values were noted, resulting in their separation into
non-impacted and slightly or highly Cd-impacted (with lower HO) animals. In gills
of impacted organisms, deep histopathological alterations and protein
overexpression of Na+/K+-ATPase and V-H+-ATPase were observed through histology
and immunolocalization, while non-impacted animals showed profiles comparable to
controls. Moreover, the osmoregulatory processes in the population living in the
Cd-contaminated site were impacted by acute Cd exposure in the laboratory as much
as for one of the two populations originating from Cd-free sites. The observed
changes did not reveal any obvious adaptive osmoregulatory phenomena at the
population scale, but they may be due to differences in fitness between
individuals and between populations in relation to the features of their
respective environments, unrelated with the presence of the metal.
PMID- 28419955
TI - Photodegradation of 4,4'-dibrominated diphenyl ether in Triton X-100 micellar
solution.
AB - This study has investigated the photochemical reactions of 4,4'-dibrominated
diphenyl ether (BDE-15) in Triton X-100 (TX-100) solution by UV light. All
photolysis experiments were performed in TX-100 solutions which were all above
critical micelle concentration (CMC). BDE-15 photodegradation follows the pseudo
first-order kinetics under various conditions. The results showed that the
degradation rates of BDE-15 increased with the increasing concentration of TX
100, and decreased when TX-100 was used in excess, because TX-100 can act as
hydrogen donor, photosensitizer and light barrier. When the pH value was in the
range of 1-11, the degradation rates increased with the increasing pH value due
to the proton effect and free radical reaction. When pH reached 13, the
corresponding degradation rate dropped significantly, which was attributed to the
decreasing surface potential of micellar retarding the degradation process. BDE
15 was debrominated into 4-dibrominated diphenyl ether (BDE-3) and diphenyl ether
(DE), subsequently. In addition, dibenzofuran (DF), ortho-hydroxydiphenyl and
para-hydroxydiphenyl were identified as another group of photoproducts,
indicating PBDEs can also undergo the photochemical rearrangement via CO bond
cleavage and recombination of the radical fragments.
PMID- 28419956
TI - Towards improved behavioural testing in aquatic toxicology: Acclimation and
observation times are important factors when designing behavioural tests with
fish.
AB - The quality and reproducibility of science has recently come under scrutiny, with
criticisms spanning disciplines. In aquatic toxicology, behavioural tests are
currently an area of controversy since inconsistent findings have been
highlighted and attributed to poor quality science. The problem likely relates to
limitations to our understanding of basic behavioural patterns, which can
influence our ability to design statistically robust experiments yielding
ecologically relevant data. The present study takes a first step towards
understanding baseline behaviours in fish, including how basic choices in
experimental design might influence behavioural outcomes and interpretations in
aquatic toxicology. Specifically, we explored how fish acclimate to behavioural
arenas and how different lengths of observation time impact estimates of basic
swimming parameters (i.e., average, maximum and angular velocity). We performed a
semi-quantitative literature review to place our findings in the context of the
published literature describing behavioural tests with fish. Our results
demonstrate that fish fundamentally change their swimming behaviour over time,
and that acclimation and observational timeframes may therefore have implications
for influencing both the ecological relevance and statistical robustness of
behavioural toxicity tests. Our review identified 165 studies describing
behavioural responses in fish exposed to various stressors, and revealed that the
majority of publications documenting fish behavioural responses report extremely
brief acclimation times and observational durations, which helps explain
inconsistencies identified across studies. We recommend that researchers applying
behavioural tests with fish, and other species, apply a similar framework to
better understand baseline behaviours and the implications of design choices for
influencing study outcomes.
PMID- 28419957
TI - Arsenic in groundwater of the Kolkata Municipal Corporation (KMC), India:
Critical review and modes of mitigation.
AB - This study represents the first comprehensive report of groundwater arsenic
contamination status in the Kolkata Municipal Corporation (KMC). During the past
23 years, 4210 groundwater samples were analysed from all 141 wards in the KMC:
14.2% and 5.2% samples had arsenic >10 MUg/l and >50 MUg/l, respectively,
representing 77 and 37 wards. The study shows that the number of arsenic
contaminated samples (and wards) in the southern part of the KMC exceeds that of
other parts of the city. The daily intake of arsenic from drinking water was
estimated as 0.95 MUg per kg bw and the cancer risk was estimated as 1425/106.
Analyses of biological samples (hair, nail and urine) showed elevated
concentrations of arsenic indicating the presence of subclinical arsenic
poisoning, predicting an enhanced lifetime cancer risk for the population in
southern part of the KMC. In the KMC, groundwater is not a sustainable source of
freshwater due to arsenic, high iron, hardness and total dissolved solids. Its
continued use is impelled by the lack of an adequate infrastructure to treat and
supply surface water and in some wards the unaccounted for water (UFW) is even
>45% incurred during distribution. The rare imposition of a water tax makes the
water supply systems unsustainable and fosters indifference to water
conservation. To mitigate the arsenic problem, continuous groundwater monitoring
for pollutants, a treated surface water supply with strict policy implications,
rainwater harvesting in the urban areas and introduction of water taxes seem to
be long-term visible solutions.
PMID- 28419958
TI - Arsenate and fluoride enhanced each other's uptake in As-sensitive plant Pteris
ensiformis.
AB - We investigated the effects of arsenate (AsV) and fluoride (F) on each other's
uptake in an As-sensitive plant Pteris ensiformis. Plants were exposed to 1) 0.1
* Hoagland solution control, 2) 3.75 mg L-1 As and 1.9, 3.8, or 7.6 mg L-1 F, or
3) 1 mg L-1 F and 3.75 mg L-1 or 7.5 mg L-1 As for 7 d in hydroponics. P.
ensiformis accumulated 14.7-32.6 mg kg-1 As at 3.75 mg L-1 AsV, and 99-145 mg kg
1 F at 1 mg L-1 F. Our study revealed that AsV and F increased each other's
uptake when co-present. At 1.9 mg L-1, F increased frond As uptake from 14.7 to
40.3 mg kg-1, while 7.5 mg L-1 As increased frond F uptake from 99 to 371 mg kg
1. Although, AsV was the predominant As species in all tissues, F enhanced AsIII
levels in the rhizomes and fronds, while the reverse was observed in the roots.
Increasing As concentrations also enhanced TBARS and H2O2 in tissues, indicating
oxidative stress. However, F alleviated As stress by lowering their levels in the
fronds. Frond and root membrane leakage were also evident due to As or F
exposure. The results may facilitate better understanding of the mechanisms
underlying the co-uptake of As and F in plants. However, the mechanisms of how
they enhance each other's uptake in P. ensiformis need further investigation.
PMID- 28419959
TI - Substance abuse in patients with bipolar disorder: A systematic review and meta
analysis.
AB - By considering the debilitating outcome of co-occurring of bipolar disorder (BD)
and substance abuse, determination of risk factors of substance use disorders
(SUD: abuse or dependence of drugs and/or alcohol) is essential to identify the
susceptible patients. The purpose of this study was to clarify the major
determinant factors of SUD among adults with BD by reviewing the relevant
literature. We systematically searched electronic databases including PubMed
(MEDLINE), EMBASE, OVID, Cochrane and Scopus for human studies addressing the co
existence of bipolar disorder and SUD. All potential published papers up to
September 2016 have been reviewed. The statistical analysis was performed using
Comprehensive Meta-analysis version 2. Male gender (Odds ratio: 2.191 (95% CI:
1.121-4.281), P 0.022), number of manic episodes (P: 0.001) and previous history
of suicidality (Odds ratio: 1.758 (95% CI: 1.156-2.674), P: 0.008) were
associated to SUD in patients with BD. SUD was not related to age, subtype of BD,
hospitalization and co-existence of anxiety disorders or psychotic symptoms. SUD
affects many aspects of BD regarding clinical course, psychopathology and
prognosis. Our study demonstrates that male gender, history of higher number of
manic episodes and suicidality are associated to higher susceptibility to SUD.
Thus, assignment of more intensive therapeutic interventions should be considered
in patients with increased risk of drug abuse to prevent development of SUD.
PMID- 28419960
TI - Preferentially enhancing anti-cancer isothiocyanates over glucosinolates in
broccoli sprouts: How NaCl and salicylic acid affect their formation.
AB - Broccoli (Brassica oleracea L. var. italica) sprouts contain glucosinolates (GLs)
that when hydrolysed yield health promoting isothiocyanates such as sulforaphane
(SF). SF content can be increased by salt (NaCl) stress, although high salt
concentrations negatively impact plant growth. Salicylic acid (SA) treatments can
attenuate the negative effects of salt on growth. To test whether sprout
isothiocyanate content could be elevated without sprout growth being compromised,
broccoli seed were germinated and grown for seven days in salt (0, 80 and 160 mM)
alone and in combination with 100 MUM SA. Increasing concentrations of salt
lowered transcript accumulation of GL biosynthetic genes which was reflected in
lowered content of Gluconapin, 4-methoxyglucobrassicin and neoglucobrassicin
glucosinolates. Other glucosinolates such as glucoraphanin did not alter
significantly. Salt (160 mM) increased transcript abundance of the GL hydrolytic
gene MYROSINASE (BoMYO) and its cofactor EPITHIOSPECIFIER MODIFIER1 (BoESM1)
whose encoded product directs MYROSINASE to produce isothiocyanate rather than
nitrile forms. SF content was increased 6-fold by the 160 mM salt treatment, but
the salt treatment reduced percentage seed germination, slowed seed germination,
and reduced sprout hypocotyl elongation. This growth inhibition was prevented if
100 MUM SA was included with the salt treatment. These findings suggest that the
increase in SF production by salt occurs in part because of increased transcript
abundance of genes in the hydrolytic pathway, which occurs independently of the
negative impact of salt on sprout growth.
PMID- 28419961
TI - Evidence towards the involvement of nitric oxide in drought tolerance of
sugarcane.
AB - Exogenous supply of nitric oxide (NO) increases drought tolerance in sugarcane
plants. However, little is known about the role of NO produced by plants under
water deficit. The aim of this study was to test the hypothesis that drought
tolerance in sugarcane is associated with NO production and metabolism, with the
more drought-tolerant genotype presenting higher NO accumulation in plant
tissues. The sugarcane genotypes IACSP95-5000 (drought-tolerant) and IACSP97-7065
(drought-sensitive) were submitted to water deficit by adding polyethylene glycol
(PEG-8000) in nutrient solution to reduce the osmotic potential to -0.4 MPa. To
evaluate short-time responses to water deficit, leaf and root samples were taken
after 24 h under water deficit. The drought-tolerant genotype presented higher
root extracellular NO content, which was accompanied by higher root nitrate
reductase (NR) activity as compared to the drought-sensitive genotype under water
deficit. In addition, the drought-tolerant genotype had higher leaf intracellular
NO content than the drought-sensitive one. IACSP95-5000 exhibited decreases in
root S-nitrosoglutathione reductase (GSNOR) activity under water deficit,
suggesting that S-nitrosoglutathione (GSNO) is less degraded and that the drought
tolerant genotype has a higher natural reservoir of NO than the drought-sensitive
one. Those differences in intracellular and extracellular NO contents and
enzymatic activities were associated with higher leaf hydration in the drought
tolerant genotype as compared to the sensitive one under water deficit.
PMID- 28419962
TI - Temporal trends of PBDEs and emerging flame retardants in belugas from the St.
Lawrence Estuary (Canada) and comparisons with minke whales and Canadian Arctic
belugas.
AB - An exponential level increase of the ubiquitous halogenated flame retardant (HFR)
class polybrominated diphenyl ether (PBDE) has been documented during the 1990s
in endangered belugas (Delphinapterus leucas) from the St. Lawrence Estuary
(SLE), Eastern Canada. The recent worldwide bans and regulations of PBDE mixtures
led to their replacement by alternative HFRs (so-called emerging HFRs) that are
increasingly being reported in various environmental compartments. There are,
however, limited knowledge on the spatial and temporal trends of PBDEs and
emerging HFRs in cetaceans, especially after restrictions on PBDE usage. The
first objective of this study was to investigate the occurrence of HFRs (35 PBDE
congeners and 13 emerging compounds) in the blubber of belugas and minke whales
(Balaenoptera acutorostrata) found dead in the Estuary or Gulf of St. Lawrence as
well as belugas from Nunavik (Canadian Arctic) collected as part of the Inuit
subsistence hunt. A second objective was to investigate the trends of HFR
concentrations in SLE beluga males between 1997 and 2013. PBDEs were the most
abundant HFRs in all three whale populations, while hexabromobenzene (HBB),
Chlordene Plus (CPlus), Dechlorane Plus (DP), and Dechlorane 604 Component B (Dec
604 CB) were quantified in the majority of blubber samples. Overall,
concentrations of emerging HFRs were notably greater in SLE belugas compared to
the two other whale populations, with the exception of DP and Dec-604 CB that
were found in greater concentrations in Canadian Arctic belugas. No significant
trend in blubber PBDE concentrations was found in SLE belugas during this 17-year
period. This suggests that global PBDE regulations are too recent to observe
changes in PBDE concentrations in belugas from this highly HFR-exposed
environment. In contrast, concentrations of HBB and CPlus in SLE belugas
decreased slightly from 1997 to 2013, while DP increased up until 2000 and
decreased slightly thereafter. The occurrence and temporal variations of PBDEs
and their replacement products in these cetaceans warrant continuous monitoring.
PMID- 28419963
TI - Acute toxicity and anti-fatigue activity of polysaccharide-rich extract from corn
silk.
AB - The aim of this study was to evaluate the safety and potential of PCS as the anti
fatigue functional food. PCS was prepared by water extracting-alcohol
precipitating method, and its chemical compositions of monosaccharide were
analyzed. Then, acute toxicity and anti-fatigue activity of PCS were evaluated.
PCS is composed of Rha, Arab, Xyl, Man, Glu, and Gal, its molar ratio is 0.17:
0.30: 0.26: 0.35: 1.00: 0.57. No mortality and general symptoms of toxicity were
observed in the PCS treated mice (7.5, 15, and 20g/kg body weight), the body
weight and food consumption were not significantly changed compared with the
normal control group. The relative weights of main organ, and biochemical
indicators also did not markedly change. PCS can significantly prolong the
duration of the swimming time to exhaustion in mice, decrease BUN, LA levels,
increase LDH activities, and the contents of HG in the PCS treated mice. The dose
of 400mg/kg body weight is the optimal dose for anti-fatigue activity both in
male and female mice. In conclusion, PCS is a promising traditional natural-based
therapeutic remedy for relieving fatigue with high safety.
PMID- 28419964
TI - Effects of Paeonia emodi on hepatic cytochrome P450 (CYP3A2 and CYP2C11)
expression and pharmacokinetics of carbamazepine in rats.
AB - Herbal medicines, dietary supplements, and other foods may pharmacokinetically
and/or pharmacodynamically interact with carbamazepine (CBZ), which could lead to
potential clinical consequences. Paeonia emodi (PE) is one of the herbs used as
complementary therapy in the treatment of epileptic patients in some cultures,
and may also be co-administered with CBZ. This study evaluates the effects of PE
on the pharmacokinetics of CBZ and determines a possible mechanism of
interaction. Rats were administered vehicle saline or PE (200mg/kg, p.o. daily
for 7days), then administered a single CBZ dose (80mg/kg, p.o.) on day 7. Plasma
samples were analyzed for CBZ concentrations using a sensitive reversed-phase
high-performance liquid chromatography (RP-HPLC) assay. Pharmacokinetic
parameters were calculated using non-compartmental analysis. The co
administration of PE with CBZ resulted in increased plasma maximum concentration
(Cmax), area under the curve (AUC0-infinity), and half-life (T1/2), by 14.61%,
48.12%, and 43.72%, respectively. The calculated oral clearance (CL/F) was
reduced by 33.54%, while the volume of distribution (Vss) was unaffected. The PE
extract also showed a significant potential to reduce CYP3A and CYP2C protein
expression by approximately 50%. Therefore, a reduction in the metabolic capacity
responsible for CBZ clearance appears to be the mechanism behind this herb-drug
interaction. Consequently, the concomitant administration of PE and CBZ should be
viewed cautiously. Further studies are needed to determine the clinical relevance
of these observations.
PMID- 28419965
TI - Chidamide in FLT3-ITD positive acute myeloid leukemia and the synergistic effect
in combination with cytarabine.
AB - Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for
treatment of T-cell lymphomas in multiple clinical trials. It has been
demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce
differentiation in leukemia cells, whereas its effect on acute myeloid leukemia
(AML) patients with FLT3-ITD mutation has not been clarified. In this study, we
found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD
positive AML cells in a concentration and time-dependent manner. We also found
chidamide had the cytotoxicity effect on FLT3-ITD positive and negative AML
cells. Moreover, with respect to relapsed/refractory patients, chidamide showed
the same effectiveness as that in de novo AML patients. Notably, chidamide
synergistically enhanced apoptosis caused by cytarabine. Our results support
chidamide alone or combine with cytarabine may be used as an alternative
therapeutic choice for AML patients especially those with FLT3-ITD mutation or
relapsed/refractory ones.
PMID- 28419966
TI - Small nucleolar RNA ACA11 promotes proliferation, migration and invasion in
hepatocellular carcinoma by targeting the PI3K/AKT signaling pathway.
AB - Emerging evidence suggests that tumorigenesis involves dysregulation of small
nucleolar RNAs (snoRNAs). However, the role of small nucleolar RNA ACA11 (ACA11)
in the development of hepatocellular carcinoma (HCC) remains unknown. Expression
of ACA11 was measured using quantitative RT-PCR in 92 HCC specimens and 7 HCC
cell lines. We found that ACA11 expression was significantly upregulated in HCC
tissues and hepatoma cell lines. This upregulation of ACA11 in HCC tumors was
significantly associated with histological grade, HBV infection, Barcelona Clinic
Liver Cancer stage, portal vein tumor thrombus and poorer patient survival.
Knockdown of ACA11 induced G0/G1 phase arrest and suppressed proliferation,
migration and invasion of HCCLM9 and SK-Hep1 cells. Low ACA11 expression resulted
in decreased HCC growth in an animal model. Conversely, transgenic expression of
ACA11 induced S phase progression and enhanced proliferation, migration and
invasion of Huh7 cells in vitro and in vivo. Finally, we found that ACA11
promoted cell growth, migration and invasion through activation of the PI3K/AKT
pathway, subsequently increasing cyclinD1 expression and inducing EMT. These
results suggest that ACA11 has an oncogenic role in HCC and may serve as a
promising prognostic biomarker and therapeutic target for patients with HCC.
PMID- 28419967
TI - Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial
efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis
and invasion in vitro.
AB - Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive
(GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive
therapy. In the present study, the potential anti-angiogenic and anti-invasive
effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+)
tumours. OLE (2mg/mL) caused a significant reduction in tumour weight,
vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004;
respectively) that was associated with reducing the expression of VEGFA, MMP-2
and MMP-9. This effect was synergistically increased in combination with
bevacizumab. Therefore, our current findings may contribute to research on drugs
that inhibit the invasiveness of GBM.
PMID- 28419968
TI - Current insights into pathogenesis of Parkinson's disease: Approach to mevalonate
pathway and protective role of statins.
AB - Although Parkinson's disease (PD) is considered as the second most common life
threatening age-related neurodegenerative disorder, but the underlying mechanisms
for pathogenesis of PD are remained to be fully found. However, a complex
relationship between genetic and environmental predisposing factors are involved
in progression of PD. Dopaminergic neuronal cell death caused by mutations and
accumulation of alpha-synuclein in Lewy bodies and neurites was suggested as the
main strategy for PD, but current studies have paid attention to the role of
mevalonate pathway in incidence of neurodegenerative diseases including PD. The
discovery may change the therapeutic protocols from symptomatic treatment by
dopamine precursors and agonists to neurodegenerative process halting drugs.
Moreover, the downstream metabolites of mevalonate pathway may be used as
diagnostic biomarkers for early diagnosis of PD. Statins, as cholesterol lowering
drugs, may ameliorate the enzyme complex dysfunction, a key step in the
progression of the neurodegenerative disorders, oxidative stress-induced damage
and neuro-inflammation. Statins exert the neuroprotective effects on striatal
dopaminergic neurons through blocking the mevalonate pathway. In the present
review, we have focused on the new approaches to pathogenesis of PD regarding to
mevalonate pathway, in addition to the previous understood mechanisms for the
disease. It tries to elucidate the novel findings about PD for the development of
future diagnostic and therapeutic strategies. Moreover, we explain the
controversial role of statins in improvement or progression of PD and the
position of these drugs in neuroprotection in PD patients.
PMID- 28419969
TI - Neurotoxic effects of silver nanoparticles and the protective role of rutin.
AB - The toxicological studies on silver nanoparticles (Ag-NPs) have become a hot
topic over the past few decades due to their unique properties on the nanoscale
and widespread in many commercial products that launched into the market
recently. This study was undertaken to shed light on Ag-NPs toxicity on
neurotransmitters with special emphasis on the impact of concurrent
administration of rutin with Ag-NPs in the experimental rats. The oral
administration of Ag-NPs in rats induced brain oxidative stress, significant
alterations in neurotransmitters and amino acids. Furthermore, transcriptional
levels of glutamatergic N-methyl-d-aspartate (NMDA) receptors, monoamino oxidases
(MAO-A, MAO-B) and metallothionein-III (MT-III) showed a significant elevation in
Ag-NPs intoxicated rats. Moreover, histological examinations revealed
astrogliosis and demyelination of neurons concomitant with neuronal degeneration
and vacuolation. Strikingly, oral administration of rutin counterbalanced the
toxic effects triggered by Ag-NPs. Taken together, our findings suggested that
oral administration of Ag-NPs induced neurotoxicity in rats and rutin mitigates
these effects.
PMID- 28419970
TI - Effect of premedication with subcutaneous adrenaline on the pharmacokinetics and
immunogenicity of equine whole IgG antivenom in a rabbit model.
AB - Subcutaneous administration of a low dose of adrenaline is used to prevent the
early adverse reactions (EARs) induced by snake antivenoms. We used a rabbit
model to study the effect of premedication with adrenaline on the potential of
antivenoms to exert therapeutic effects and to induce late adverse reactions. We
found that premedication with adrenaline did not change the heart rate or blood
pressure of normal rabbits, but reduced the rise in temperature in rabbits
previously sensitized with antivenom. Pharmacokinetic studies suggest that
premedication with adrenaline does not affect the ability of the antivenom to
exert the initial control of envenomation nor the susceptibility of rabbits to
develop recurrence of antigenemia and envenomation. Our results also indicate
that it is unlikely that premedication with adrenaline decreases the incidence of
late reactions induced by the antivenom administration, although it reduces the
extent of early reactions.
PMID- 28419971
TI - miR-493-5p suppresses hepatocellular carcinoma cell proliferation through
targeting GP73.
AB - Aberrant expression of miRNAs has been documented to play critical roles in the
development and progression of hepatocellular carcinoma (HCC). However, the
expression pattern, functional roles and regulatory mechanism of miR-493-5p in
HCC have not been addressed. Herein, we found that miR-493-5p was significantly
downregulated in HCC tissues and was tightly associated with tumor size, tumor
differentiation grade and TNM stage of HCC patients. Overexpression of miR-493-5p
inhibited HCC cell proliferation, arrested cell cycle in G0/G1 phase and induced
cell apoptosis. Bioinformatical analysis and luciferase reporter assay further
proved that Golgiprotein73 (GP73), an oncogene which was generally overexpressed
in HCC, acted as a novel target of miR-493-5p. MiR-493-5p could inhibit GP73 both
mRNA and protein expression. Moreover, overexpression of GP73 could reverse the
inhibitory effects of miR-493-5p mediated HCC cell proliferation. In addition,
upregulated GP73 in HCC tissues was inversely correlated with the miR-493-5p
expression levels in the HCC tissues. Collectively, our present study
demonstrates that miR-493-5p is downregulated in HCC and it can suppress the
proliferation of HCC cells, partly at least, via directly targeting GP73.
Besides, this study provides a novel insight into the mechanism of
hepatocarcinogenesis and a promising blueprint for miR-493-5p-GP73 axis-oriented
treatment of HCC.
PMID- 28419972
TI - Neprilysin inhibitors: A new hope to halt the diabetic cardiovascular and renal
complications?
AB - Diabetes is an enormous and ever-growing calamity and a global public health
threat of the 21st century. Besides insulin and oral hypoglycaemic drugs,
blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for
the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which
are the leading causes of disability and death among diabetic patients.
Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the
bioavailability of natriuretic peptides and benefits the cardio-renal system.
Omapatrilat, a dual angiotensin-converting enzyme (ACE) and NEP inhibitor has
been reported to show superior anti-hypertensive, anti-atherosclerotic, insulin
sensitizing, cardiovascular and renoprotective effects to ACE inhibitors in
experimental animal models for diabetes. In clinical trials on hypertensive
subjects Omapatrilat increased the risk of angioedema due to which its further
development as anti-hypertensive drug was hampered. This event prompted the
development of angiotensin receptor neprilysin inhibitors (ARNi). The first
representative of ARNi, LCZ696 (Sacubitril/ Valsartan) halted cardiovascular and
renal functional decline and hence protected against CKD and CVD. Recently,
LCZ696 was approved by U.S. Food and Drug Administration for the treatment of
heart failure. This concise review intends to summarise the currently available
reports on NEPi as a therapeutic intervention to treat CVD and CKD associated
with diabetes.
PMID- 28419973
TI - Antibacterial, antifungal and antimycobacterial compounds from cyanobacteria.
AB - Infections from multidrug resistant (MDR) pathogenic bacteria, fungi and
Mycobacterium tuberculosis remain progressively intractable. The search of
effective antimicrobials from other possible non-conventional sources against MDR
pathogenic bacteria, fungi and mycobacteria is call of the day. This review
considers 121 cyanobacterial compounds or cyano-compounds with antimicrobial
activities. Chemical structures of cyano-compounds were retrieved from ChemSpider
and PubChem databases and were visualized by the software ChemDraw Ultra.
Chemical information on cyano-compounds pertaining to Lipinski rules of five was
assessed. The reviewed cyano-compounds belong to the following chemical classes
(with examples): alkaloids (ambiguine isonitriles and 12-epi-hapalindole E
isonitrile), aromatic compounds (benzoic acid and cyanobacterin), cyclic
depsipeptides (cryptophycin 52 and lyngbyabellin A), cyclic peptides (calophycin
and tenuecyclamides), cyclic undecapeptides (kawaguchipeptins and lyngbyazothrin
A), cyclophane (carbamidocyclophane), extracellular pigment (nostocine A), fatty
acids (alpha-dimorphecolic acid and majusculonic acid), linear peptides
(muscoride A), lipopeptides (fischerellins and scytonemin A), nucleosides
(tolytoxin and tubercidin), phenols (ambigols and 4-4'-hydroxybiphenyl),
macrolides (scytophycin A and tolytoxin), polyketides (malyngolide and
nostocyclyne), polyphenyl ethers (crossbyanol A), porphinoids (tolyporphin J) and
terpenoids (noscomin and scytoscalarol). Cyanobacteria appear to be a diverse
source of compounds with antimicrobial activity. Further attention is required to
elucidate whether those could be applied as pharmaceuticals.
PMID- 28419974
TI - Prediction and feature analysis of intron retention events in plant genome.
AB - Alternative splicing (AS) is a major contributor to increase the potential
informational content of eukaryotic genomes by creating multiple mRNA species and
proteins from a single gene. In plants, up to 60% genes are alternatively spliced
and the most common type of AS is intron retention (IR). Genomic analyses of IR
have illuminated its crucial role in shaping the evolution of genomes, in the
control of developmental processes, and in the dynamic regulation of the
transcriptome to influence phenotype. To explore the relationship between the
sequence feature and the formation mechanism of IR, we statistically analyzed the
retained introns and proposed an improved random forest-based hybrid method to
predict intron retention events in plant genome. The results indicate that IR has
significant relationship with individual introns which have weaker 5' splice
sites, lower GC content and less termination codon occurrence. By the method we
proposed, 93.48% retained introns can be correctly distinguished from
constitutive introns. Strikingly, our study will facilitate a better
understanding of underlying mechanisms involved in intron retention.
PMID- 28419975
TI - Animal models for neuropsychiatric disorders: prospects for circuit intervention.
AB - Monogenic animal models for psychiatric diseases have enabled researchers to
dissect the relationship between certain candidate genes, neural circuit
abnormalities, and behavioral phenotypes along development. Early reports of
phenotypic reversal after genetic restoration in mouse models sparked hope that
genetic defects do not damage circuits irreversibly in early-onset disorders.
However, further studies have suggested that only some circuits exhibit this
plasticity, while many others require proper gene function during development.
This review focuses on what we have learned from a few evolutionarily conserved
circuit-phenotype relationships and their developmental windows to illustrate
their importance when considering intervention strategies.
PMID- 28419976
TI - Microbial extracellular enzymes in biogeochemical cycling of ecosystems.
AB - Extracellular enzymes, primarily produced by microorganisms, affect ecosystem
processes because of their essential roles in degradation, transformation and
mineralization of organic matter. Extracellular enzymes involved in the cycling
of carbon (C), nitrogen (N) and phosphorus (P) have been widely investigated in
many different ecosystems, and several enzymes have been recognized as key
components in regulating C storage and nutrient cycling. In this review, it was
the first time to summarize the specific extracellular enzymes related to C
storage and nutrient cycling for better understanding the important role of
microbial extracellular enzymes in biogeochemical cycling of ecosystems.
Subsequently, ecoenzymatic stoichiometry - the relative ratio of extracellular
enzyme, has been reviewed and further provided a new perspective for
understanding biogeochemical cycling of ecosystems. Finally, the new insights of
using microbial extracellular enzyme in indicating biogeochemical cycling and
then protecting ecosystems have been suggested.
PMID- 28419977
TI - Investigation of As(V) removal from acid mine drainage by iron (hydr) oxide
modified zeolite.
AB - In this work, the synthesis of iron (hydr) oxide modified zeolite was achieved
through precipitation of iron on the zeolite. The structure and surface
morphology of iron (hydr) oxide modified zeolite (IHOMZ) was studied by scanning
electron microscopy (SEM), coupled with an energy-dispersive X-ray spectroscopy
(EDX), and Fourier transform infrared (FT-IR) spectra. The efficiency of IHOMZ
was then investigated through batch technique for the extraction of As(V) from
mine waste water. The optimum parameters for maximum As(V) adsorption were: an
initial As(V) concentration (10 mg L-1), adsorbent dosage (3.0 g), contact time
(90 min) and temperature (53 degrees C). The initial pH of the solution had no
compelling effect on As(V) adsorption by IHOMZ. However, adsorption capacity was
significantly affected by the solution temperature with 53 degrees C registering
the maximum removal efficiency. The thermodynamic parameters: Entropy (DeltaS
degrees = 0.00815 kJ (K mol)-1), variation of the Gibbs free energy (DeltaG
degrees ) and enthalpy (DeltaH degrees = 9.392 kJ mol-1) of As(V) adsorption
onto IHOMZ system signified a non-spontaneous and endothermic process. It was
noted that Freundlich isotherm model exhibited a better fit to the equilibrium
experimental data, implying that the adsorption process occurred on a
heterogeneous surface. The kinetic data from As(V) adsorption experiments was
depicted by the pseudo-second-order kinetic model (R2 > 0.999), suggesting a
chemisorption adsorption process. The experimental batch equilibrium results
indicated that IHOMZ could be used as an effective sorbent for As(V) ion
extraction from acid mine drainage.
PMID- 28419978
TI - Dissolved oxygen, stream temperature, and fish habitat response to environmental
water purchases.
AB - Environmental water purchases are increasingly used for ecological protection. In
Nevada's Walker Basin (western USA), environmental water purchases augment
streamflow in the Walker River and increase lake elevation of terminal Walker
Lake. However, water quality impairments like elevated stream temperatures and
low dissolved oxygen concentrations also limit ecosystems and species, including
federally-threatened Lahontan cutthroat trout. In this paper, we prioritize water
volumes and locations that most enhance water quality for riverine habitat from
potential environmental water rights purchases. We monitored and modeled
streamflows, stream temperatures, and dissolved oxygen concentrations using River
Modeling System, an hourly, physically-based hydrodynamic and water quality
model. Modeled environmental water purchases ranged from average daily increases
of 0.11-1.41 cubic meters per second (m3/s) during 2014 and 2015, two critically
dry years. Results suggest that water purchases consistently cooled maximum daily
stream temperatures and warmed nightly minimum temperatures. This prevented
extremely low dissolved oxygen concentrations below 5.0 mg/L, but increased the
duration of moderate conditions between 5.5 and 6.0 mg/L. Small water purchases
less than approximately 0.71 m3/s per day had little benefit for Walker River
habitat. Dissolved oxygen concentrations were affected by upstream environmental
conditions, where suitable upstream water quality improved downstream conditions
and vice versa. Overall, this study showed that critically dry water years
degrade environmental water quality and habitat, but environmental water
purchases of at least 0.71 m3/s were promising for river restoration.
PMID- 28419979
TI - Clinical profile of persistent genito-pelvic postpartum pain.
AB - : OBJECTIVE*: the primary aim was to describe the pain characteristics of
persistent genito-pelvic postpartum pain (PPP) and compare these characteristics
by mode of delivery. The secondary aim was to incorporate psychosocial variables
into the conceptualization of PPP by exploring the relationship among postpartum
depressive symptoms, fatigue, and PPP. DESIGN: cross-sectional study design.
SETTING: online survey. PARTICIPANTS: 106 women recruited from the community who
gave birth within twelve months prior to completing the survey. MEASUREMENTS AND
FINDINGS: questionnaire regarding sociodemographic information, pregnancy and
childbirth variables, depressive symptoms (Edinburgh Postnatal Depression Scale),
and fatigue (Fatigue Symptom Checklist). Women who were >=3 months postpartum and
indicated they were still experiencing any genito-pelvic pain from childbirth
were provided questions about their current pain experience. Twenty-seven (25.5%)
women were between 3-12 months postpartum and currently experiencing PPP. The
intensity of pain was mild, and had multiple locations and triggers. Compared to
women whose acute pain resolved after childbirth, women with PPP were more likely
to have had a Caesarean section (15.2% versus 33.3%). Other birth-related (i.e.,
epidural/spinal anesthesia use during vaginal birth) and psychosocial variables
(income) also differentiated women with PPP from women whose gentio-pelvic pain
resolved. Postpartum fatigue independently predicted PPP (Odds ratio = 4.7),
while postpartum depressive symptoms did not. KEY CONCLUSIONS: PPP was quite
prevalent in this sample, and while the intensity of pain was on average, mild,
the pain was widespread in terms of location and triggers. Multiple
biopsychosocial factors differentiated women with persistent postpartum pain from
those women whose pain resolved. IMPLICATIONS FOR PRACTICE: PPP is a common
health concern for new mothers in the first year postpartum, and may be best
addressed by health care professionals using a multidimensional approach, which
focuses on the psychosocial aspects of pain.
PMID- 28419980
TI - Evaluation of GLUT1 variation in non-acquired focal epilepsy.
AB - Brain glucose transport is dependent on glucose transporter 1 (GLUT1), encoded by
the solute carrier family 2 member 1 (SLC2A1) gene. Mutations in SLC2A1 cause
GLUT1 deficiency which is characterized by a broad spectrum of neurological
phenotypes including generalized epilepsy, motor disorders, developmental delay
and microcephaly. Recent case reports suggest SLC2A1 mutations can contribute to
non-acquired focal epilepsy (NAFE) but interrogation of a large patient cohort
has not been reported. We studied 200 patients with NAFE (126 with temporal lobe
epilepsy) comprising 104 females and 96 males with a mean age of onset of 18
years. Polymerase chain reaction (PCR) and Sanger sequencing was performed to
detect variants in all 10 coding exons and splice site regions of the SLC2A1
gene. We did not detect any pathogenic mutations in SLC2A1 in this cohort. Our
data suggests that the frequency of GLUT1 mutations in NAFE is low. Limitations
of this study include the mean age of onset and cohort size. Future research
should focus on subpopulations of focal epilepsy with lower age of seizure onset
particularly with co-existent movement disorders in which GLUT1 mutations may
play a more important role.
PMID- 28419981
TI - Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An
Observational Multicenter International Study.
AB - BACKGROUND: Hyponatremia is a frequent and potentially life-threatening adverse
side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry
database focuses on current management practices of thiazide-associated
hyponatremia (TAH) and compares differences between TAH and syndrome of
inappropriate antidiuretic hormone secretion (SIADH). METHODS: We analyzed 477
patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] <=130 mEq/L)
who were receiving a thiazide diuretic. Of these, 118 met criteria for true
thiazide-induced hyponatremia (TIH). RESULTS: Thiazide was withdrawn immediately
after hyponatremia was diagnosed only in 57% of TAH; in these patients, the
median rate of [Na+] change (Deltadaily[Na+]) was significantly higher than those
with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8]
mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%),
fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic
saline (5.2%). Hypertonic saline produced the greatest Deltadaily[Na+] (8.0[6.4]
mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5
[3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction
was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of
hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic
saline. Although there are highly significant differences in the biochemical
profiles between TIH and SIADH, no predictive diagnostic test could be derived.
CONCLUSIONS: Despite its high incidence and potential risks, the management of
TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment
success. Hypertonic saline is most effective in correcting hyponatremia but
associated with a high rate of overly rapid correction. We could not establish a
diagnostic laboratory-based test to differentiate TIH from SIADH.
PMID- 28419983
TI - Pam3CSK4 Induces MMP-9 Expression in Human Monocytic THP-1 Cells.
AB - BACKGROUND: Matrix metalloproteinase (MMP)-9 is known to degrade the
extracellular matrix and increased MMP-9 levels are related with the pathogenesis
of many inflammatory conditions including obesity. Pam3CSK4 is a synthetic
triacylated lipopeptide (LP) which is a potent activator of immune cells and
induces cytokine production. However, it is unclear whether Pam3CSK4 is able to
induce MMP-9 expression in monocytic cells. We, therefore, determined MMP-9
production by Pam3CSK4-treated THP-1 cells and also investigated the signal
transduction pathway(s) involved. METHODS: MMP-9 expression was determined by
real-time qPCR and ELISA. MMP-9 activity was assessed by zymography. THP-1 cells,
THP1-XBlueTM cells, THP1-XBlueTM-defMyD cells, anti-TLR2 mAb and selective
pharmacological inhibitors were used to study signaling pathways involved.
Phosphorylated and total proteins were detected by western blotting. RESULTS:
Pam3CSK4 induced MMP-9 expression (P<0.05) at both mRNA and protein levels in
human monocytic THP-1 cells. Increased NF-kappaB/AP-1 activity was detected in
Pam3CSK4-treated THP-1 cells and MMP-9 production in these cells was
significantly suppressed by pre-treatment with anti-TLR2 neutralizing antibody or
by inhibition of clathrin-dependent endocytosis. Also, MyD88-/- THP-1 cells did
not express MMP-9 following treatment with Pam3CSK4. Inhibition of JNK, MEK/ERK,
p38 MAPK and NF-kappaB significantly suppressed MMP-9 gene expression (P<0.05).
CONCLUSION: Pam3CSK4 induces MMP-9 production in THP-1 cells through the TLR
2/MyD88-dependent mechanism involving MEK/ERK, JNK, p38 MAPK and NF-kappaB/AP-1
activation.
PMID- 28419982
TI - Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure.
AB - BACKGROUND: Although high resting heart rate (RHR) is known to be associated with
an increased risk of mortality and hospital admission in patients with heart
failure, the relationship between RHR and ischemic stroke remains unclear. This
study is aimed at investigating the relationship between RHR and ischemic stroke
in patients with heart failure in sinus rhythm. METHODS: We examined 2,060
patients with systolic heart failure in sinus rhythm from the Warfarin versus
Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from
baseline electrocardiogram, and was examined as both a continuous variable and a
categorical variable using quartiles. Ischemic strokes were identified during
follow-up and adjudicated by physician review. RESULTS: During 3.5 +/- 1.8 years
of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an
ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was
observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups;
22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and
21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional
hazards analysis revealed that RHR was significantly associated with ischemic
stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR
<64/beats/min; p = 0.038), along with a history of stroke or transient ischemic
attack and left ventricular ejection fraction. CONCLUSIONS: In contrast to its
beneficial effect on mortality and hospital re-admissions, lower RHR may increase
the risk of ischemic stroke in patients with systolic heart failure in sinus
rhythm.
PMID- 28419984
TI - Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a
Receptor-Dependent Mechanism.
AB - BACKGROUND: Though vitiligo is a common depigmentary disorder, it still
represents a substantial therapeutic challenge. Therapeutic options are limited
in part due to its uncertain etiology. OBJECTIVE: Because recent studies suggest
that histamine stimulates melanogenesis in vitro, we determined here whether
topical histamine stimulates repigmentation in patients with stable, nonsegmental
vitiligo. METHODS: A total of 23 otherwise normal volunteers with vitiligo,
including 14 males and 9 females aged 6-59 years (mean age 29.2 +/- 2.8), were
enrolled in this study. 1% histamine in distilled water was applied to the
lesions twice daily for 5 weeks, while comparable lesions, treated with distilled
water alone, served as the controls. The melanin index was measured on the
uninvolved and lesional skin sites before and after 5 weeks of treatments using
the melanin/erythema probe connected to a Courage-Khazaka MPA5 (Cologne,
Germany). Changes in epidermal permeability barrier were also assessed at the
same time point. To determine whether histamine-induced repigmentation is
receptor-dependent, both ears of C57BL/6J mice were treated topically with 5%
cimetidine, a histamine type 2 receptor (H2r) antagonist, twice daily for 10
days. One hour after each cimetidine application, the right ear was treated
topically with 10% histamine, while vehicle alone was applied to the left ear.
Changes in melanin index were measured 24 h after the last application of
histamine and vehicle as described in the human study. RESULTS: In patients with
vitiligo treated with vehicle alone for 5 weeks, the melanin index remained
unchanged, while topical histamine treatment increased the melanin index by 38%
(p < 0.001 vs. both vehicle and pretreatment), which was paralleled by a >60%
reduction in lesion surface area. Moreover, topical histamine accelerated
permeability barrier recovery. No adverse events were observed following
histamine applications. In mice, topical histamine significantly increased the
melanin index, while topical co-applications of the H2r antagonist (cimetidine)
prevented the expected histamine-induced increase in melanin index. CONCLUSIONS:
These studies indicate that topical histamine or an H2r agonist could be useful
for treating nonsegmental vitiligo, but further clinical studies in large
populations will be required to validate the efficacy and safety of this
approach.
PMID- 28419985
TI - Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat
Traumatic Brain Injury.
AB - BACKGROUND: Traumatic brain injury (TBI) can be complicated by TBI-triggered
acute lung injury (ALI), in which inflammation plays a central role. It has been
reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate
TBI; however, its function in TBI-caused ALI has not been reported yet. METHODS:
In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight
drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and
bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and
eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the
lungs were harvested for immunofluorescence staining and qRT-PCR analysis.
RESULTS: At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased
wet/dry ratios, decreased total BALF protein, and attenuated the histological
signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the
accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF
alpha, IL-6, IL-1beta and iNOS in the lung. CONCLUSIONS: We identified the
protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a
potent candidate for systemic therapy in TBI patients.
PMID- 28419986
TI - Hypodysfibrinogenemia with a Heterozygous Mutation of gammaCys326Ser by the Novel
Transversion of TGT to TCT in a Patient with Pulmonary Thromboembolism and Right
Ventricular Thrombus.
AB - We encountered a 45-year-old Japanese man who suffered from pulmonary
thromboembolism and huge right ventricular thrombus after inferior vena cava
(IVC) filter implantation without apparent thrombus in either the deep veins or
inside the IVC filter. The biochemical data showed a discrepancy in the level of
fibrinogen between the immunological and thrombin time methods, suggesting
hypodysfibrinogenemia. The sequencing of the fibrinogen gamma-chain gene (FGG)
revealed a novel heterozygous missense mutation in exon 8 - a TGT to TCT
transversion in codon 326 - resulting in an amino acid substitution of serine for
cysteine (gammaCys326Ser). The characterization of the protein did not show known
mechanisms for thrombosis in dysfibrinogenemia, such as dimer or albumin-binding
complex formation. In summary, the current case with a life-threatening
thrombotic event was found to have a novel heterozygous missense mutation
resulting in gammaCys326Ser, which was suggested as a predisposing factor of the
thrombosis. Known mechanisms responsible for thrombosis in the current case were
not demonstrated, suggesting other mechanisms including superimposing inherited
and/or acquired risk factors. When a patient presents with unusual thrombosis
such as breakthrough pulmonary embolism and huge thrombus in the right ventricle,
as in the current case, the laboratory process for heritable thrombophilia should
be considered.
PMID- 28419987
TI - Extracellular Matrix Mediates BMP-2 in a Model of Temporomandibular Joint
Osteoarthritis.
AB - Temporomandibular joint (TMJ) osteoarthritis (OA) is a complex disease that
affects both cartilage and subchondral bone. It is accompanied by loss of
extracellular matrix (ECM) and may be controlled by bone morphogenetic protein-2
(BMP-2). We analyzed the effect of BMP-2 in both cartilage and subchondral bone
in a TMJ-OA animal model that is deficient in biglycan (Bgn) and fibromodulin
(Fmod) (Bgn-/-Fmod-/-). Whole mandibles were dissected from 3-week-old wild-type
(WT) and Bgn-/-Fmod-/- mice and incubated with and without 250 ug/mL BMP-2 for 2
days using an explant culture system. Condyle growth was measured by microCT and
the expression levels of cartilage and bone-related genes were analyzed using RT
PCR or by immunohistochemistry from condyles that contained an intact
cartilage/subchondral bone interface. Osteoclast activity was estimated by
tartrate-resistant acid phosphatase (TRAP) staining and by TRAP, Rankl, and
Adamts4 mRNA expression levels. Our results showed that most parameters examined
were slightly up-regulated in WT samples treated with BMP-2, and this up
regulation was significantly enhanced in the Bgn-/-Fmod-/- mice. The up
regulation of both catabolic and anabolic agents did not appear to positively
affect the overall growth of Bgn-/-Fmod-/- condyles compared to WT controls. In
summary, the up-regulation of both anabolic and catabolic genes in the WT and Bgn
/-Fmod-/- TMJs treated with BMP-2 suggests that BMP increases matrix turnover in
the condyle, and, further, that Bgn and Fmod could have protective roles in
regulating this process.
PMID- 28419989
TI - Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute
Ischemic Stroke Patients.
AB - BACKGROUND: Low magnesium levels are associated with an elevated risk of stroke.
In this study, we investigated the association between magnesium levels on
hospital admission and in-hospital mortality in acute ischemic stroke (AIS)
patients. METHODS: A total of 2,485 AIS patients, enrolled from December 2013 to
May 2014 across 22 hospitals in Suzhou city, were included in this study. The
patients were divided into 4 groups according to their level of admission
magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and
Q4 (>=0.98 mmol/L). Cox proportional hazard model was used to estimate the effect
of magnesium on all-cause in-hospital mortality in AIS patients. RESULTS: During
hospitalization, 92 patients (3.7%) died from all causes. The lowest serum
magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in
hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56;
p-trend < 0.001). After adjusting for age, sex, time from onset to hospital
admission, baseline National Institutes of Health Stroke Scale score, and other
potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; p-trend = 0.014).
Sensitivity and subgroup analyses further confirmed a significant association
between lower magnesium levels and a high risk of in-hospital mortality.
CONCLUSIONS: Decreased serum magnesium levels at admission were independently
associated with in-hospital mortality in AIS patients.
PMID- 28419988
TI - Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor for In-Hospital
Mortality in Spontaneous Intracerebral Hemorrhage.
AB - BACKGROUND AND PURPOSE: Stroke-associated immunosuppression and inflammation are
increasingly recognized as factors that trigger infections and thus, potentially
influence the outcome after stroke. Several studies demonstrated that elevated
neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse
outcomes in patients with ischemic stroke. However, little is known about the
impact of NLR on short-term mortality in intracerebral hemorrhage (ICH). METHODS:
This observational study included 855 consecutive ICH-patients. Patient
demographics, clinical, laboratory, and in-hospital measures as well as
neuroradiological data were retrieved from institutional databases. Functional 3
months-outcome was assessed and categorized as favorable (modified Rankin Scale
[mRS] 0-3) and unfavorable (mRS 4-6). We (i) studied the natural course of NLR in
ICH, (ii) analyzed parameters associated with NLR on admission (NLROA), and (iii)
evaluated the clinical impact of NLR on mortality and functional outcome.
RESULTS: The median NLROA of the entire cohort was 4.66 and it remained stable
during the entire hospital stay. Patients with NLR >=4.66 showed significant
associations with poorer neurological status (National Institute of Health Stroke
Scale [NIHSS] 18 [9-32] vs. 10 [4-21]; p < 0.001), larger hematoma volume on
admission (17.6 [6.9-47.7] vs. 10.6 [3.8-31.7] mL; p = 0.001), and more
frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 [74.2%] vs. 275/428
[64.3%]; p = 0.002). Patients with an NLR under the 25th percentile (NLR <2.606)
compared to patients with NLR >2.606 - presented with a better clinical status
(NIHSS 12 [5-21] vs. 15 [6-28]; p = 0.005), lower hematoma volumes on admission
(10.6 [3.6-30.1] vs. 15.1 [5.7-42.3] mL; p = 0.004) and showed a better
functional outcome (3 months mRS 0-3: 82/214 [38.3%] vs. 185/641 [28.9%]; p =
0.009). Patients associated with high NLR (>=8.508 = above 75th-percentile)
showed the worst neurological status on admission (NIHSS 21 [12-32] vs. 12 [5
23]; p < 0.001), larger hematoma volumes (21.0 [8.6-48.8] vs. 12.2 [4.1-34.9] mL;
p < 0.001), and higher proportions of unfavorable functional outcome at 3 months
(mRS 4-6: 173/214 vs. 418/641; p < 0.001). Further, NLR was linked to more
frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; p =
0.001, sepsis: 78/214 vs. 116/641; p < 0.001), and increased c-reactive-protein
levels on admission (p < 0.001; R2 = 0.064). Adjusting for the above-mentioned
baseline confounders, multivariable logistic analyses revealed independent
associations of NLROA with in-hospital mortality (OR 0.967, 95% CI 0.939-0.997; p
= 0.029). CONCLUSIONS: NLR represents an independent parameter associated with
increased mortality in ICH patients. Stroke physicians should focus intensely on
patients with increased NLR, as these patients appear to represent a population
at risk for infectious complications and increased short-mortality. Whether these
patients with elevated NLR may benefit from a close monitoring and specially
designed therapies should be investigated in future studies.
PMID- 28419990
TI - Effects of Estradiol on Autophagy and Nrf-2/ARE Signals after Cerebral Ischemia.
AB - BACKGROUND/AIMS: Estradiol (EST) reduces the risk of stroke and decreases the
incidence and progression of the disease because of its neuroprotective roles in
inhibiting cell death that occurs in response to a variety of neuronal stimuli
such as inflammation and oxidative stress. In this study, we determined the role
played by autophagy and Nrf2-ARE signal pathways in the hippocampus regions in
modulating cerebral ischemia under different EST conditions. METHODS: Western
blot analysis and ELISA were used to determine the protein expression of
autophagy and Nrf2-ARE pathways; and the levels of pro-inflammatory cytokines
(PICs) and a key marker of oxidative stress. RESULTS: Lacking of EST amplifies
autophagy and attenuates Nrf2-ARE pathway in the hippocampus CA1 region. Blocking
autophagy alleviates neurological deficits following cerebral ischemia with
lacking of EST levels and the effects of autophagy are associated with PIC and
oxidative stress. CONCLUSIONS: EST influences the protein expression of autophagy
and Nrf2-ARE signaling in the brain, which is linked to the pathophysiological
processes of PICs and oxidative stress. Moreover, inhibition of autophagy plays a
beneficial role in modulating neurological deficits after cerebral ischemia
observed under conditions of a lower level of EST.
PMID- 28419991
TI - Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal
Damage in a Rat Model of Vascular Dementia.
AB - OBJECTIVES: This study was intended to investigate whether treatment with
resveratrol and melatonin alone or in combination can exert neurorestorative
effects in a rat model of vascular dementia. METHODS: Briefly, male Wistar rats
were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by
surgery. After 4 weeks, the cognitive deficits were assessed using the Morris
water maze and novel object recognition tests. The biochemical parameters of
oxidative stress and inflammation were also assessed. RESULTS: Rats in the BCCAO
group showed cognitive deficits, accompanied by oxidonitrosative stress,
neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in
the hippocampus region. Moreover, the acetylcholinesterase activity in the
hippocampus was found to be increased in the BCCAO group compared to the sham
group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg)
alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a
significant improvement in the cognitive deficits induced by BCCAO, accompanied
by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion
in the hippocampus region. Additionally, the treatment with melatonin and
resveratrol significantly decreased acetylcholinesterase activity compared to in
the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of
hippocampal protein. CONCLUSION: These results emphasize that coadministration of
melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia
through changes in BDNF expressions.
PMID- 28419992
TI - Extended Small-Dose Platelet Transfusions in Multitransfused Hemato-Oncological
Patients: A Single-Center Experience.
AB - BACKGROUND: Refractoriness to platelet transfusion, prevalent among 15-20% of
hemato-oncological patients, is associated with multitransfusions and inferior
outcomes. We evaluated the effectiveness of extended slow-dose transfusion (ESDT)
in increasing platelet increments in multitransfused patients. METHODS: Patients
treated after the implementation of ESDT were compared with historical controls
treated with standard single-donor platelet (SDP) transfusions. Cohorts of early
and late recipients were assembled for comparison, i.e. the 8th or 9th and 11th
platelet unit per patient, respectively. Patients in the ESDT group received
transfusions equal to half an SDP unit, administered over 4 h. Effectiveness was
defined as a higher corrected count increment (CCI) at 1, 12, and 24 h after
transfusion. RESULTS: In the early-recipients cohort, 24-h-posttransfusion
increments were available for 29 ESDT patients and 6 standard patients, and did
not differ significantly between the groups (p = 0.078). The 24-h-posttransfusion
increment was available for 20 ESDT patients and 7 standard patients in the late
recipients cohort. The CCI was significantly higher in the ESDT group (p =
0.042). ABO compatibility improved the CCI (p = 0.01). CONCLUSIONS: ESDT
demonstrated slightly higher increments at 24 h after transfusion in late
recipients, suggesting this could be a cost-effective approach for the treatment
of thrombocytopenic multitransfused hemato-oncological patients.
PMID- 28419993
TI - Reduction in Peripheral CD19+CD24hCD27+ B Cell Frequency Predicts Favourable
Clinical Course in XELOX-Treated Patients with Advanced Gastric Cancer.
AB - BACKGROUND: Accumulating evidence suggests that regulatory B cells (Bregs) play
an important role in modulating the immune response to tumours. Our previous
study indicated that a small percentage of peripheral CD19+CD24hCD27+ Breg cells
slowed gastric cancer progression in XELOX-treated patients. Here, we further
investigated the relationship between dynamic changes in circulating Breg cells
and the clinical course in XELOX-treated gastric cancer patients. METHODS: A
total of 52 patients with advanced gastric cancer were enrolled in this study.
The frequencies of CD19+CD24hCD27+ cells in peripheral blood were tested before
(as a baseline) and 9 weeks after administration of oxaliplatin and capecitabine
(XELOX). The primary endpoint of the study was progression-free survival time
(PFS) of the patients. The overall survival (OS) and adverse events of
chemotherapy were also recorded. RESULTS: The median PFS of patients was 6 months
(95% CI, 5.27-6.73) with effective rate of 46.2%. The percentage of
CD19+CD24hCD27+ cells in lymphocytes ranged from 0.007% to 1.94%, with a median
value of 0.45%. The median percentage of CD19+CD24hCD27+ lymphocytes was 0.59%
(0.01%-6.02%) 9 weeks after treatment. There were no significant differences for
this index. However, the patients with decreased Breg frequencies after XELOX
treatment had a longer PFS time (7.0 months vs. 5.0 months, p=0.01) than those
with increased Breg frequencies. CONCLUSION: Patients with downtrend of
CD19+CD24hCD27+ B lymphocytes during early stages of chemotherapy relative to
their initial values had longer PFS times, and this could be used to predict the
efficacy of chemotherapy and help physicians adjust treatments accordingly.
PMID- 28419994
TI - Degradation of Mcl-1 through GSK-3beta Activation Regulates Apoptosis Induced by
Bufalin in Non-Small Cell Lung Cancer H1975 Cells.
AB - BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often
overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to
induce apoptosis in various tumor cells. However, there is no report showing that
bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation
was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis
was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression
of apoptosis-associated proteins in H1975 cells was detected by western blotting.
The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation
assay. RESULTS: Cell growth was inhibited by bufalin in a time and dose-dependent
manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades
and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished
bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA
expression in H1975 cells, but strongly promoted Mcl-1 protein degradation.
Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and
blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect
NOXA protein levels, but downregulated the expression of p-GSK-3beta. GSK-3
inhibitor and GSK-3beta siRNA resulted in increased levels of Mcl-1 and reversed
the bufalin-induced Mcl-1 degradation. CONCLUSION: Bufalin induced cell apoptosis
in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of
Mcl-1 via GSK-3beta activation was involved in bufalin-induced apoptosis.
PMID- 28419995
TI - Hemolytic Uremic Syndrome and Kidney Transplantation: A Case Series and Review of
the Literature.
AB - BACKGROUND: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin
producing Escherichia coli (STEC) infection or it can be defined as atypical HUS
(aHUS) if it is related to uncontrolled complement activation. aHUS is
characterized by a high incidence of recurrence after kidney transplantation, and
it can also occur de novo in transplant recipients. Eculizumab is used both to
prevent and to treat aHUS following kidney transplantation. In this paper, we
report our centre experience and we present 4 cases of HUS in patients who
underwent kidney transplantation. METHODS: This is a single-center experience
about HUS development in transplanted patients. RESULTS: Patient 1 with end-stage
renal disease (ESRD) due to STEC-HUS undergoing kidney transplantation without
prophylactic therapy with eculizumab. Patient 2 with HUS secondary to an episode
of diarrhea at 8 years old. After a slow progression to ESRD, she underwent
kidney transplantation and she received prophylactic therapy with eculizumab due
to the presence of anti-complement factor H antibodies. Patient 3 underwent pre
emptive living donor ABO-incompatible kidney transplantation and developed HUS
secondary to antibody-mediated rejection. Patient 4 developed de novo HUS 16
years after kidney transplantation without a known cause. CONCLUSION: The correct
diagnosis of HUS and the identification of the complement component alterations
in case of aHUS are important parameters required to predict the risk of post
transplant recurrence of the disease. In the cases we reported, eculizumab has
been found to be effective both to prevent and to treat aHUS following kidney
transplantation.
PMID- 28419996
TI - Polydimethyl Siloxane as an Internal Tamponade for Vitreoretinal Surgery.
AB - PURPOSE: To report the efficacy and safety of polydimethyl siloxane (Siluron
Xtra(r)) as an internal tamponade. DESIGN: Audit and adverse event screening of
procedures (March 2014-2015). METHODS: Patients who had undergone vitreoretinal
procedures with Siluron Xtra(r) tamponade were retrospectively analysed with
respect to anatomical outcome, visual outcomes, and perioperative complications,
in particular intraocular pressure. INCLUSION CRITERIA: all patients who had
undergone Siluron Xtra(r) tamponade. EXCLUSION CRITERIA: No cases were excluded;
however, there were no paediatric or pregnant patients within this cohort. All
vitreoretinal cases were included, including retinal detachments, but also
trauma, endophthalmitis, and intraocular foreign bodies. RESULTS: Twenty-eight
patients had polydimethyl siloxane as an intraocular tamponade; 24 retinal
detachments (83% complicated by proliferative vitreoretinopathy >=grade C), 12
had previous failed surgery, and 4 had procedures for intraocular lymphoma,
endophthalmitis, or trauma. Follow-up was 14-20 months, and mean duration of
tamponade was 6.8 months (3-12 months). Anatomical success was 79% after
polydimethyl siloxane injection, 58% 3 months following removal (14/24), 5 remain
with long-term tamponade, and 5 with redetachment under tamponade required
further intervention. Five required topical anti-glaucomatous agents, and 1
following trauma required glaucoma surgery. Cataract developed in 3/6 phakic
patients, and visible emulsification occurred in a single patient. CONCLUSION:
Polydimethyl siloxane seems to be an acceptable alternative tamponade agent for
the management of complex retinal detachments with comparable anatomical success
and comparable rates of raised intraocular pressure to other low-viscosity
silicone oil agents, but more importantly, with a lower rate of emulsified oil
related complications, which is important particularly for cases requiring long
term tamponade.
PMID- 28419997
TI - Examining the Causal Role of Leptin in Alzheimer Disease: A Mendelian
Randomization Study.
AB - BACKGROUND: Observational evidence regarding the role of leptin in Alzheimer
disease (AD) is conflicting. We sought to determine the causal role of
circulating leptin and soluble plasma leptin receptor (sOB-R) levels in AD using
a separate-sample Mendelian randomization study. METHODS: Single nucleotide
polymorphisms (SNPs) independently and solely predictive of log-transformed
leptin (rs10487505 [LEP], rs780093 [GCKR], rs900400 [CCNL1], rs6071166 [SLC32A1],
and rs6738627 [COBLL1]) and of sOB-R (rs1137101 [LEPR], rs2767485 [LEPR], and
rs1751492 [LEPR]) levels (ng/mL) were obtained from 2 previously reported genome
wide association studies. We obtained associations of leptin and sOB-R levels
with AD using inverse variance weighting with fixed effects by combining Wald
estimates for each SNP. Sensitivity analyses included using weighted median and
MR-Egger methods and repeating the analyses using only SNPs of genome-wide
significance. RESULTS: Using inverse variance weighting, genetically predicted
circulating leptin levels were not associated with AD, albeit with wide
confidence intervals (CIs): odds ratio (OR) 0.99 per log-transformed ng/mL; 95%
CI 0.55-1.78. Similarly, the association of sOB-R with AD was null using inverse
variance weighting (OR 1.08 per log-transformed ng/mL; 95% CI 0.83-1.41). Results
from our sensitivity analyses confirmed our findings. CONCLUSIONS: In this first
Mendelian randomization study estimating the causal effect of leptin on AD, we
did not find an effect of genetically predicted circulating leptin and sOB-R
levels on AD. As such, this study suggests that leptin is unlikely to be a major
contributor to AD, although the wide CIs preclude a definitive assessment.
PMID- 28419998
TI - Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin
Chemotherapy.
AB - BACKGROUND AND AIMS: Several studies have indicated that cisplatin (cis
diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC).
However, the underlying cofactors affecting the increased urinary excretion
remain unclear. The present study was performed to evaluate the dynamics of LC in
plasma and urine after CDDP chemotherapy and to examine the relations with
clinical parameters, such as gender, body mass index (BMI), and renal function.
METHODS: Twenty-two patients treated with CDDP therapy were selected. Blood and
urine samples were taken from patients before starting CDDP treatment (day 0), on
the next day (day 1), and on the seventh day (day 7). We measured plasma and
urine concentrations of total, free, and acyl-LC, and examined the relationships
with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular
filtration rate, and change in creatinine concentration after CDDP
administration. RESULTS: Both urinary and plasma concentrations of 3 types of LC
increased markedly on day 1 and subsequently reverted to the pre-CDDP level on
day 7. There was a positive correlation between the % changes in plasma and urine
LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant
relations were seen in other clinical parameters. CONCLUSIONS: CDDP transiently
increased plasma LC levels. The mechanism seemed to involve recruitment for
marked urinary loss of LC. However, these changes in plasma and urinary LC levels
were not related to clinical factors, suggesting that the dynamics of LC were
independent of preexisting physical parameters.
PMID- 28419999
TI - Gender Differences and Stroke Outcomes.
PMID- 28420000
TI - (-)-Epicatechin Suppresses Angiotensin II-induced Cardiac Hypertrophy via the
Activation of the SP1/SIRT1 Signaling Pathway.
AB - BACKGROUND/AIMS: Flavonol (-)-epicatechin (EPI) is present in high amounts in
cocoa and tea products, and has been shown to exert beneficial effects on the
cardiovascular system. However, the precise mechanism of EPI on cardiomyocyte
hypertrophy has not yet been determined. In this study, we examined whether EPI
could inhibit cardiac hypertrophy. METHODS: We utilised cultured neonatal mouse
cardiomyocytes and mice for immunofluorescence, immunochemistry, qRT-PCR, and
western blot analyses. RESULTS: 1uM EPI significantly inhibited 1uM angiotensin
II (Ang II)-induced increase of cardiomyocyte size, as well as the mRNA and
protein levels of ANP, BNP and beta-MHC in vitro. The effects of EPI were
accompanied with an up-regulation of SP1 and SIRT1, and were abolished by SP1
inhibition. Up-regulation of SP1 could block Ang II-induced increase in
cardiomyocyte size, as well as the mRNA and protein levels of ANP, BNP and beta
MHC, and increase the protein levels of SIRT1 in vitro. Moreover, 1 mg/kg body
weight/day EPI significantly inhibited mouse cardiac hypertrophy induced by Ang
II, which could be eliminated by SP1 inhibition in vivo. CONCLUSION: Our data
indicated that EPI inhibited AngII-induced cardiac hypertrophy by activating the
SP1/SIRT1 signaling pathway.
PMID- 28420001
TI - Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced
Histone H3 Lysine9 Dimethylation in BEAS-2B Cells.
AB - BACKGROUND: Nickel compounds are well-established human carcinogens with weak
mutagenic activity. Histone methylation has been proposed to play an important
role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT)
decreases histone methylation in several cancer cells by altering the cellular
ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the
role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS
2B cells were exposed to different concentrations of nickel chloride (NiCl2) for
72 h or 200 MUM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9)
mono-, di-, and trimethylation and NNMT protein levels were measured by western
blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen
activated protein kinase 3 (MAP2K3) and dickkopf1 (DKK1), were determined by qPCR
analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+) to
reduced NAD (NADH) and SAM/SAH ratio were determined. RESULTS: Exposure of BEAS
2B cells to nickel increased H3K9 dimethylation (H3K9me2), suppressed the
expressions of H3K9me2-associated genes (MAP2K3 and DKK1), and induced NNMT
repression at both the protein and mRNA levels. Furthermore, over-expression of
NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio.
Additionally, the NADH oxidant phenazine methosulfate (PMS) not only reversed the
nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2.
CONCLUSIONS: These findings indicate that the repression of NNMT may underlie
nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.
PMID- 28420002
TI - Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China.
AB - BACKGROUND: Psoriasis is an autoimmune disease with genetic and environmental
factors. Based on the roles of STATs (signaling transducers and activators of
transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are
associated with psoriasis. OBJECTIVES: To study the association between STAT gene
polymorphisms and psoriasis in the northeastern Chinese population. METHODS:
Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769,
rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011
and rs3024974 in STAT6, using SNaPshot methods. The genotype, allele, and
haplotype frequencies were compared between 400 psoriasis patients and 398
healthy individuals in northeastern China. RESULTS: rs744166GG in STAT3 and
rs7574865TT in STAT4 had higher frequencies in the case than the control group,
suggesting these 2 genotypes increase the susceptibility to psoriasis (p < 0.05).
Three haplotypes (H3, H6, and H7) were found to be associated with psoriasis in
the study (p < 0.05). CONCLUSIONS: These results indicate a role of STAT genes in
the pathogenesis of psoriasis.
PMID- 28420003
TI - Retrospective Analysis of the Risk Factors for Grade IV Neutropenia in
Oesophageal Cancer Patients Treated with a Docetaxel, Cisplatin, and 5
Fluorouracil Regimen.
AB - BACKGROUND: Previous Japanese trials of the docetaxel, cisplatin, and 5
fluorouracil regimen for oesophageal cancer have demonstrated that a large
proportion of patients also develop grade IV neutropenia. Our aim was to examine
the risk factors for neutropenia in patients treated with this regimen. METHODS:
We retrospectively analysed the risk factors for developing grade IV neutropenia
in 66 patients with oesophageal cancer using a multivariate analysis. RESULTS:
After administering the docetaxel, cisplatin, and 5-fluorouracil regimen, 49
patients (74.2%) developed grade IV neutropenia. Grade IV neutropenia was
significantly associated with platelet count (p < 0.01), alanine transaminase
level (p = 0.05), and proton-pump inhibitor administration (p < 0.05). Receiver
operating characteristic curve analysis confirmed a platelet count of 290 *
103/MUL as the optimal diagnostic cut-off value for grade IV neutropenia. The
receiver operating characteristic area for grade IV neutropenia was increased by
including patients that were administered a proton-pump inhibitor and alanine
transaminase level (updated model; sensitivity and specificity, 75.5 and 88.2%,
respectively). CONCLUSIONS: Our findings suggest that a platelet count is the
most significant predictor of grade IV neutropenia.
PMID- 28420004
TI - Hearing Loss and Risk of Mild Cognitive Impairment and Dementia: Findings from
the Singapore Longitudinal Ageing Study.
AB - AIM: To investigate the associations between hearing loss and prevalent and
incident mild cognitive impairment (MCI), dementia and MCI or dementia (all
cases). METHODS: Cross-sectional and longitudinal analyses of baseline and follow
up data were performed in a population-based cohort. The baseline sample of 2,599
adults aged >=55 included 1,515 cognitively normal subjects who were followed up
to 8 years. Hearing loss at baseline was determined by the whispered voice test,
and MCI and dementia by Mini-Mental State Examination screening, Clinical
Dementia Rating scale, neurocognitive tests, MRI, and panel consensus diagnosis.
RESULTS: Hearing impairment was associated with increased prevalence of dementia
(odds ratio = 3.63, 95% confidence interval [CI] 1.16-11.4, p = 0.027) but not
MCI alone or all cases of MCI or dementia, adjusted for sex, age, ethnicity,
education, central obesity, hypertension, diabetes, dyslipidemia, smoking,
alcohol, leisure time activity, cardiac diseases, and depressive symptoms. Among
participants who were cognitively normal at baseline, those with hearing
impairment were more likely to develop MCI or dementia (hazard ratio [HR] = 2.30,
95% CI 1.08-4.92, p = 0.032). Hearing loss was associated with elevated but
statistically nonsignificant estimates of adjusted HR (1.85, 95% CI 0.78-4.40)
for incident MCI alone. CONCLUSIONS: Hearing loss is independently associated
with prevalent dementia and incident MCI or dementia.
PMID- 28420005
TI - Thiazide-Associated Hyponatremia: A Major Dilemma Affecting Treatment.
PMID- 28420006
TI - Increased Visfatin Expression Is Associated with Nuclear Factor-kappaB in Obese
Ovalbumin-Sensitized Male Wistar Rat Tracheae.
AB - OBJECTIVE: To investigate the effects of diet-induced obesity on the expression
of nuclear factor-kappaB (NF-kappaB) and visfatin messenger RNA in male Wistar
rats' tracheae after sensitization with ovalbumin (OVA). MATERIALS AND METHODS:
Twenty male Wistar rats were divided into 4 groups (n = 5 for each group), which
included a control group fed a normal diet (ND) and groups fed normal diet, OVA
sensitized (S+ND); high-fat diet (HFD) only (diet-induced obesity); and high-fat
diet, OVA-sensitized (S+HFD). All animals were fed for 8 weeks with standard chow
or a high-fat diet, and then were sensitized and challenged with OVA or saline
for another 4 weeks as per the above groups. The rats were anesthetized, after
which the necks were exposed and the tracheae isolated and examined for
expression levels of NF-kappaB and visfatin mRNA with the real-time polymerase
chain reaction method. Data were compared between the different groups using one
way analysis of variance. RESULTS: The expression level of NF-kappaB mRNA in the
S+HFD group was 2.67, which was statistically higher than the levels in the ND
(0.96; p = 0.001), S+ND (1.86; p = 0.05), and HFD (1.26; p = 0.001) groups. Also,
the visfatin mRNA expression level in the S+HFD group was 4.21, which was higher
than the levels in the ND (0.92), S+ND (1.79), and HFD (2.20) (p = 0.001) groups.
CONCLUSION: In this study, the expression levels of NF-kappaB and visfatin were
markedly higher in the S+HFD group in comparison to the other groups. These
findings indicate that alternative signaling pathways might be activated in diet
induced obesity associated with the OVA-sensitized animal model and could be
responsible for possible altered sensitization phenotype.
PMID- 28420007
TI - Accessory Spleen in the Greater Omentum: Embryology and Revisited Prevalence
Rates.
AB - PURPOSE: To investigate in a large sample the prevalence rates of accessory
spleens located in the greater omentum and to explain the embryological
background and the vascular supply of this rare congenital disorder. METHODS:
Evaluation of the presence of accessory spleens located in the greater omentum
was performed in 5 different international anatomical centers investigating a
total of 1,045 body donors. Arterial and venous blood supply and the precise
location of the respective vasculature within the splenic ligaments are described
based on dissection of this rare condition in a male specimen. RESULTS: The
reported prevalence rates from 5 different centers were: 0.5% (out of 380 body
donors), 0% (out of 230 donors), 0% (out of 200 donors), 2% (out of 200 donors),
and 0% (out of 35 donors). The cumulative prevalence rate obtained from 1,045
anatomical dissections was 0.6%. The identified accessory spleen measured 3 * 3 *
2.5 cm and was located in the left upper abdominal quadrant. A vascular stag 7.5
cm in length was identified within the gastro-splenic ligament, containing an
artery and a vein piercing the greater omentum from posterior. CONCLUSION: An
accessory spleen located in the greater omentum is a rare congenital disorder.
Physicians should be aware of the fact that in patients without any
representative symptom history a nodular mass located within the greater omentum
could be an accessory spleen.
PMID- 28420008
TI - C-reactive protein and cold-pressor tolerance in the general population: the
Tromso Study.
AB - The aim of this study was to examine whether increases in severity of subclinical
inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased
experimental pain sensitivity, measured by cold-pressor tolerance, and to test
whether this relationship is independent of chronic pain. A large population
based study from 2007 to 2008, the sixth Tromso Study, provided data from 12,981
participants. For the present analysis, complete data for 10,274 participants
(age: median 58 years) were available. The main outcome measure was cold-pressor
tolerance, tested by placing the dominant hand in circulating cold water (3
degrees C) for a maximum of 106 seconds. Cox proportional hazard models, treating
hand withdrawal during the cold-pressor test as the event and enduring the full
test time as censored data, were used to investigate the relationship between hs
CRP levels (<=3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model
was controlled for age, sex, education, body mass index, smoking status, alcohol
consumption, emotional distress, statin usage, and self-reported presence of
chronic pain. Additional analysis was performed in participants without chronic
pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance
(hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001),
adjusted for age and sex. This relationship remained essentially unaltered after
controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001),
as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P <
0.001). The present data show that subclinical inflammation is related to
increased pain sensitivity, suggesting a potential role of inflammation in
experimental pain which may be of importance for the development of clinical
pain.
PMID- 28420009
TI - Temporal summation and motor function modulation during repeated jaw movements in
patients with temporomandibular disorder pain and healthy controls.
AB - Temporal summation of nociceptive inputs may be an important pathophysiological
mechanism in temporomandibular disorders (TMD) pain; however, it remains unknown
how natural jaw function relates to underlying pain mechanisms. This study
evaluated changes in pain and movement patterns during repeated jaw movements in
patients with painful temporomandibular joints (TMJ) compared with healthy
controls. Twenty patients with TMD with TMJ pain, and an anterior disk
displacement without reduction and 20 age- and gender-matched healthy volunteers
were included. Participants performed 20 trials (4 * 5 sessions) of standardized
and repeated mandibular movements, and scored the movement-associated pain
intensity on 0 to 10 numeric rating scale in addition to measurements of jaw
movements. Patients with TMJ pain reported higher baseline pain compared to the
control group for all types of jaw movements (P = 0.001) and significant
increases in numeric rating scale pain scores by repetition of jaw movements (P <
0.001), which was not observed in the control group (P > 0.05). Jaw total opening
distance (P = 0.030), maximum opening velocity (P = 0.043) and average closing
velocity (P = 0.044) in the TMJ pain group were significantly reduced during the
repeated movements. In the control group, however, total opening distance (P =
0.499), maximum opening velocity (P = 0.064), and average closing velocity (P =
0.261) remained unchanged, whereas average opening velocity (P = 0.040) and
maximum closing velocity (P = 0.039) increased. The study demonstrates that
repeated jaw movements constitute a sufficient and adequate stimulation for
triggering temporal summation effects associated with significant inhibition of
motor function in painful TMJs. These findings have practical implications for
diagnosis of TMD pain and for more mechanism-driven management protocols in the
future.
PMID- 28420010
TI - Consumption of Methamphetamine during Pregnancy - Transgenerational Substance
Misuse?
PMID- 28420011
TI - Noninvasive Ventilation in Newborns <= 1,500 g after Tracheal Extubation:
Randomized Clinical Trial.
PMID- 28420012
TI - Vitamin B6-Responsive Epilepsy due to a Novel KCNQ2 Mutation.
AB - Mutations in KCNQ2, encoding for subunits of potassium channels, are known to
cause neonatal epileptic encephalopathy (NEE). Therapeutic options for these
children are often limited. Recently, there are indications that some patients
with KCNQ2 NEE show seizure response to vitamin B6 (VB6) therapy. We present a
young infant with severe KCNQ2 encephalopathy resulting from a novel de novo
mutation (c.1023G>C; p.(Gln341His)). In our patient, VB6 responsiveness could be
demonstrated clearly by remarkable seizure-response to VB6 therapy and seizure
exacerbation to discontinuation of VB6 therapy. The pathophysiology of VB6
response in potassium channel mutations is not understood. Some hypothetical
mechanisms are currently in discussion. To identify the group of patients who
benefits from VB6 therapy, further investigations are necessary.
PMID- 28420013
TI - [Febrile Urinary Tract Infections: When are they an Emergency?]
PMID- 28420014
TI - [Febrile Urinary Tract Infections: When are they an Emergency?]
AB - Urinary tract infections should be suspected in every febrile infant until proven
otherwise. While older children and adolescents mostly present with classical
features such as dysuria, flank pain and/or abdominal pain, secondary enuresis or
pollakiuria, diagnosing infants or newborns, who are incapable of describing or
pinpointing pain, can be much more challenging. As such, an infection with
gradual and subtle onset may result in fulminant disease and emergency
situations. In children with urinary tract infections and known mechanical or
functional obstructions of the urinary tract, adequate drainage of the infected
urinary tract may be necessary (e. g. nephrostomy, ureteral stent or
transurethral catheter).
PMID- 28420015
TI - [Editor's Comment].
PMID- 28420016
TI - ?
PMID- 28420017
TI - ?
PMID- 28420018
TI - ?
PMID- 28420019
TI - ?
PMID- 28420020
TI - [Harvesting Grafts for Reconstruction of the Tympanic Membrane].
PMID- 28420021
TI - ?
PMID- 28420022
TI - [Severe Bleeding from the Middle Ear Cavity after Myringotomy: Review Based on a
Case Report].
AB - Report of a rare case of severe bleeding from the middle ear cavity after
myringotomy. On the basis of the case report, the procedure for such bleeding is
discussed in the context of the literature. A 6-year-old boy received a revision
myringotomy in an ambulant setting. During the procedure a severe bleeding
occurred. The external auditory canal was adequately packed. The patient was
extubated and transferred to the clinic as an emergency. Computer tomography of
the temporal bone showed the anatomical variant of a dehiscent high jugular bulb,
which had been injured. Because no rebleeding occurred, the packing of the ear
canal was removed and an explorative tympanoscopy was performed on the third
postoperative day. When the tympanomeatal flap was lifted, the defect in the
jugular bulb was found. The lesion was covered with Tutopatch(r) pads and fibrin
glue and the auditory canal was packed again. After removal of the packing three
weeks postoperatively a properly healed situs was found. No further measures were
taken. The injury of a dehiscent jugular bulb in the course of ear surgeries
leads to a massive hemorrhage. The case describes the diagnostic and therapeutic
procedure for this relatively rare but severe complication.
PMID- 28420023
TI - [A Blocked Frontal Sinus with Orbital Swelling].
PMID- 28420024
TI - [From the Expert's Office: Resection of Thyroid Tissue Instead of Zenker's
Diverticulum - A Medical Malpractice].
PMID- 28420025
TI - [Recent Developments Towards Molecularly Targeted Therapy of Head and Neck
Cancer].
PMID- 28420026
TI - ?
PMID- 28420027
TI - ?
PMID- 28420028
TI - Intrauterine Ultrasound-Guided Laser Coagulation of the Feeding Artery in Fetal
Bronchopulmonary Sequestration.
PMID- 28420029
TI - Interlobar Artery Resistive Index predicts Acute-on-Chronic Liver Failure
Syndrome in Cirrhotic Patients with Acute Decompensation.
AB - INTRODUCTION: Patients with acutely decompensated (AD) cirrhosis are at risk for
developing acute-on-chronic liver failure (ACLF) syndrome. This syndrome is
associated with a high short-term mortality rate. The aim of our study was to
identify reliable early predictors of developing ACLF in cirrhotic patients with
AD. PATIENTS AND METHODS: We assessed 84 cirrhotic patients admitted for AD
without ACLF on admission. We performed routine blood testing and detailed
ultrasound Doppler studies of systemic arteries and mayor abdominal veins and
arteries. We also calculated liver-specific and intensive care unit predictive
scores. The area under the ROC curve (AUROC) was calculated for all variables
that were significantly different between patients who developed ACLF and those
who did not. Sensitivity, specificity, positive and negative predictive values,
as well as diagnostic accuracy predicting the short-term development of ACLF were
determined. RESULTS: of the 84 patients, 23 developed ACLF whereas 61 did not.
In the univariate analysis, serum levels of creatinine and urea, prothrombin time
ratio, MELD score, portal vein and femoral artery flow velocity as well as the
renal and interlobar artery resistive indices (RI) were associated with the short
term development of ACLF. However, only interlobar artery RI had independent
predictive value in the multivariate analysis. The AUROC value for RI of the
interlobar arteries was 0.9971. CONCLUSION: On the first day of admission,
ultrasound measurement of the RI of the interlobar arteries recognizes with high
predictive accuracy those cirrhotic patients admitted with AD who will develop
ACLF during hospital admission.
PMID- 28420030
TI - Role of endoscopy in primary sclerosing cholangitis: European Society of
Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the
Liver (EASL) Clinical Guideline.
AB - 1 ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic
resonance cholangiography (MRC) should be preferred over endoscopic retrograde
cholangiopancreatography (ERCP).Moderate quality evidence, strong recommendation.
2 ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is
equivocal or contraindicated in patients with persisting clinical suspicion of
PSC. The risks of ERCP have to be weighed against the potential benefit with
regard to surveillance and treatment recommendations.Low quality evidence, weak
recommendation. 6 ESGE/EASL suggest that, in patients with an established
diagnosis of PSC, MRC should be considered before therapeutic ERCP.Weak
recommendation, low quality evidence. 7 ESGE/EASL suggest performing endoscopic
treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies)
of suspected significant strictures identified at MRC in PSC patients who present
with symptoms likely to improve following endoscopic treatment.Strong
recommendation, low quality evidence. 9 ESGE/EASL recommend weighing the
anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a
case-by-case basis.Strong recommendation, moderate quality evidence.Biliary
papillotomy/sphincterotomy should be considered especially after difficult
cannulation.Strong recommendation, low quality evidence. 16 ESGE/EASL suggest
routine administration of prophylactic antibiotics before ERCP in patients with
PSC.Strong recommendation, low quality evidence. 17 EASL/ESGE recommend that
cholangiocarcinoma (CCA) should be suspected in any patient with worsening
cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant
stricture, particularly with an associated enhancing mass lesion.Strong
recommendation, moderate quality evidence. 19 ESGE/EASL recommend ductal sampling
(brush cytology, endobiliary biopsies) as part of the initial investigation for
the diagnosis and staging of suspected CCA in patients with PSC.Strong
recommendation, high quality evidence.
PMID- 28420031
TI - The ventromedial hypothalamic nucleus in the zebra finch (Taeniopygia guttata):
Afferent and efferent projections in relation to the control of reproductive
behavior.
AB - Sex-specific mating behaviors occur in a variety of mammals, with the medial
preoptic nucleus (POM) and the ventromedial hypothalamic nucleus (VMH) mediating
control of male and female sexual behavior, respectively. In birds, likewise, POM
is predominantly involved in the control of male reproductive behavior, but the
degree to which VMH is involved in female reproductive behavior is unclear. Here,
in male and female zebra finches, a combination of aromatase immunohistochemistry
and conventional tract tracing facilitated the definition of two separate but
adjacent nuclei in the basal hypothalamus: an oblique band of aromatase-positive
(AR+) neurons, and ventromedial to this, an ovoid, aromatase-negative (AR-)
nucleus. The AR- nucleus, but not the AR+ nucleus, was here shown to receive a
projection from rostral parts of the thalamic auditory nucleus ovoidalis and from
the nucleus of the tractus ovoidalis. The AR- nucleus also receives an
overlapping, major projection from previously uncharted regions of the medial
arcopallium and a minor projection from the caudomedial nidopallium. Both the AR-
and the AR+ nuclei project to the intercollicular nucleus of the midbrain. No
obvious sex differences in either the pattern of AR immunoreactivity or of the
afferent projections to the AR- nucleus were observed. The significance of these
results in terms of the acoustic control of avian reproductive behavior is
discussed, and a comparison with the organization of VMH afferents in lizards
suggests a homologous similarity of the caudal telencephalon in sauropsids.
PMID- 28420032
TI - Identifying a subset of patients with DCIS who have a low likelihood of residual
disease at surgical excision following a core needle biopsy.
AB - BACKGROUND AND OBJECTIVES: Current randomized controlled trials are investigating
the outcomes of non-surgical treatment for patients with ductal carcinoma in situ
(DCIS). We sought to evaluate pre-operative factors associated with no residual
disease at definitive resection following a core needle biopsy (CNB) diagnosis of
DCIS. METHODS: Eight hundred and thirty-four operations for DCIS were performed
at our institution between January 2004 and October 2014. We evaluated patient
and biopsy tumor characteristics to determine pre-operative factors associated
with no residual disease at surgical resection using uni- and multivariable
analyses. RESULTS: Sixty-nine patients (8%) had no residual disease on final
pathology. On multivariable analysis, low- or intermediate-grade lesions, <1 cm
in size on mammography, and lesions where >=90% of calcifications were removed
correlated with finding no residual disease on final pathology, c-statistic 0.84.
Of the 14 patients with all three low-risk factors, 36% had no residual disease
on final pathology. CONCLUSIONS: Although our multivariable analysis performed
well, its clinical utility would be limited as we were unable to identify a
subset of patients with DCIS in whom the probability of finding no residual
disease is low enough to consider routine use of non-surgical management.
PMID- 28420033
TI - The current clinical knowledge on the treatment of gambling disorder: A summary.
AB - Gambling disorder (GD) is a topical problem in developed countries and may be
present in 1-3% of the general population. The pathophysiology of this disorder
is largely unknown but it shares similarities to other behavioral addictions.
Multiple neurotransmitter systems, including dopaminergic, serotonergic,
noradrenergic, glutamatergic, and opioidergic, have been implicated in GD. Based
on available articles, only the opioid antagonist naltrexone has been documented
to demonstrate clinical efficacy in multiple studies including double-blind
studies. Nalmefene, another opioid antagonist, may be active as well but its dose
response effect remains unclear. Contrarily, current test results do not support
the therapeutic use of any antidepressant drug. Some positive data has been made
available supporting the use of N-acetylcystein, but more studies are needed to
confirm this. No clear or definite information is currently available for other
drugs.
PMID- 28420034
TI - A fluorescence in situ hybridization-based screen allows rapid detection of
adverse cytogenetic alterations in patients with acute myeloid leukemia.
AB - In adult acute myeloid leukemia (AML), the karyotype of the leukemic cell is
among the strongest prognostic factors. The Medical Research Council (MRC) and
the European LeukemiaNet (ELN) classifications distinguish between favorable,
intermediate and adverse cytogenetic risk patients who differ in their treatment
response and overall survival. Conventional cytogenetic analyses are a mandatory
component of AML diagnostics but they are time-consuming; therefore, therapeutic
decisions in elderly patients are often delayed. We investigated whether a
screening approach using a panel of seven fluorescence in situ hybridization
(FISH) probes would allow rapid identification of adverse chromosomal changes. In
a cohort of 334 AML patients, our targeted FISH screening approach identified 80%
of adverse risk AML patients with a specificity of 99%. Incorporating FISH
screening into diagnostic workup has the potential to accelerate risk
stratification and treatment selection, particularly in older patients. This
approach may allow therapeutic decisions more quickly, which benefits both
patients and physicians and might save costs.
PMID- 28420035
TI - Prospective series of reconstruction of complex composite mandibulectomy defects
with double island free fibula flap.
AB - BACKGROUND: A double island free fibula (DIFF) flap can be used for
reconstruction of through-and-through or complex mandibulectomy defects, but
prospective studies are lacking. METHODS: Prospective analysis of all double skin
paddle fibula flaps performed from 2010 to 2016. RESULTS: Overall, 16 patients
underwent reconstruction with a DIFF flap (average age: 59.1 years). One patient,
who underwent a DIFF flap and developed osteoradionecrosis, requiring a second
flap. Thirteen patients were males, and 7 had a history of smoking, 13 had prior
radiation, and 14 had prior chemotherapy. The most common primary pathology was
squamous cell carcinoma (n = 13). Reconstruction using the DIFF was predominantly
for mandible reconstruction with one patient undergoing reconstruction following
a orbitomaxillectomy. Complications included infection (n = 2), hematoma (n = 1),
and donor site complications were limited. Two patients developed venous
congestion requiring re-exploration, and both flaps were successfully salvaged.
One patient lost the external skin paddle requiring a pectoralis muscle flap, and
there were no total flap losses. CONCLUSIONS: The DIFF flap is a reliable option
that can reconstruct complex composite defects often obviating the need for a
second free flap, thereby decreasing operating time, added donor site morbidity,
and the need for additional recipient vessels.
PMID- 28420036
TI - Dedifferentiated chondrosarcoma: A survival analysis of 159 cases from the SEER
database (2001-2011).
AB - BACKGROUND AND OBJECTIVES: Dedifferentiated chondrosarcoma is a rare malignancy
with reported 5-year overall survival rates ranging from 7% to 24%. The purpose
of this investigation is to determine the overall survival of dedifferentiated
chondrosarcoma in a modern patient series and how it is impacted by patient
demographics, tumor characteristics, and surgical treatment factors. METHODS:
This is a retrospective review of the Surveillance, Epidemiology, and End Results
(SEER) database from 2001 to 2011. Kaplan Meier analyses were used for overall
and disease-specific survival. Univariable and multivariable cox regression
models were used to identify prognostic factors. RESULTS: Five year overall- and
disease-specific survival was 18% (95% CI: 12-26%) and 28% (95% CI: 18-37%),
respectively. Individuals with extremity tumors had a worse prognosis than
individuals with a primary tumor in the chest wall or axial skeleton (HR 0.20,
95% CI: 0.07-0.56; P = 0.002 and HR 0.60, 95% CI: 0.36-0.99; P = 0.04,
respectively). Patients with AJCC stage III or IV disease (HR 2.51, 95% CI: 1.50
4.20; P = 0.001), tumors larger than 8 cm (HR 2.17, 95% CI: 1.11-4.27; P =
0.046), metastatic disease at diagnosis (HR 3.25, 95% CI: 1.98-5.33; P < 0.001),
and those treated without surgical resection (amputation: HR 0.43, 95% CI 0.23
0.80; P = 0.01; limb salvage/non-amputation resection: HR 0.41, 95% CI: 0.24
0.69; P = 0.001) had a significant increase in risk of mortality. CONCLUSIONS:
The overall prognosis of dedifferentiated chondrosarcoma is poor with a 5-year
overall survival of 18%. Patients with a primary tumor located in the chest wall
had a better prognosis. Tumors larger than 8 cm, presence of metastases at
diagnosis, and treatment without surgical resection were significant predictors
of mortality.
PMID- 28420037
TI - Does surgery or radiation provide the best overall survival in Ewing's sarcoma? A
review of the National Cancer Data Base.
AB - BACKGROUND AND OBJECTIVES: There is continuing debate regarding the ideal
modality for local control of the primary tumor for patients with Ewing's
sarcoma. The primary aim of this study is to investigate the impact of the method
of local control on overall survival in patients with Ewing's sarcoma. METHODS:
The National Cancer Data Base was used to identify patients <40 years of age with
high-grade Ewing's sarcoma of bone. A Kaplan-Meier survival analysis was
performed at 2, 5, and 10 years. Factors with a level of significance of P < 0.1
at the 5-year time point were included in a multivariate Cox proportional hazards
model. RESULTS: Diminished 5-year survival was noted for patients with metastatic
disease, local control with radiation alone, age >=18 years, tumor size >8 cm,
and male sex while controlling for tumor site. Surgery alone was consistently the
method of local control that resulted in the highest overall survival.
CONCLUSIONS: Surgery alone resulted in the best overall survival for patients
with Ewing's sarcoma of bone. The results of this investigation provide support
to the approach of surgical resection with negative margins when possible.
PMID- 28420038
TI - Retrospective evaluation of coyote attacks in dogs: 154 cases (1997-2012).
AB - OBJECTIVE: To describe the clinical presentation and outcome of known attacks in
client-owned dogs caused by the common coyote, Canis latrans. DESIGN:
Retrospective observational study. SETTING: Private referral hospital. ANIMALS:
One hundred fifty-four client-owned dogs known to be attacked by coyotes.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Records from a private
referral hospital from May 1997 through December 2012 were reviewed. Time of day
and month/season of year, signalment, body temperature, heart rate, respiratory
rate, body weight, location and severity of wounds inflicted, common injuries,
length of hospitalization, necessity of surgical wound repair under anesthesia,
antimicrobial use and mortality were recorded. Eighty-six percent of dogs
presenting following coyote attack weighed <10 kg. Overall mortality rate was
15.6%. Dogs with bite wounds to the thorax had the highest mortality at 21.3%.
Criteria for systemic inflammatory response syndrome (SIRS) based on admission
vital signs were met in 58.8% of dogs and the presence of SIRS was significantly
associated with mortality (P < 0.001). Common coyote-induced injuries included
rib fracture (38/154; 24.6%), pulmonary contusion (30/154; 19.4%), tracheal tear
(18/154; 11.6%), pneumothorax (16/154; 10.3%), abdominal wall hernia (9/154;
5.8%), and abdominal penetrating wounds (8/146; 5.5%). Dogs <10 kg were
significantly more likely to incur wounds to multiple body parts or sustain
abdominal penetrating wounds. The presence of rib fracture was significantly
associated with mortality. Frequency of coyote attacks over the time of this
study increased by 330%. CONCLUSIONS: Coyote attacks on dogs are a problem in
Southern California and are associated with substantial morbidity and mortality,
especially in dogs with wounds to the thorax. Aggressive management involving
surgical wound repair was associated with survival to discharge.
PMID- 28420039
TI - Utilizing Salmonella to treat solid malignancies.
AB - Despite intensive research into novel treatment strategies for cancer, it remains
the second most common cause of death in industrialized populations. Pancreatic
ductal adenocarcinoma (PDAC) is a highly aggressive disease with dismal
prognosis. Currently, surgical resection offers the best chance for extended
survival, yet recurrence remains high and is associated with poor outcome.
Systemic treatment has evolved from non-specific, cytotoxic chemotherapy to the
use of cancer-targeting agents, profoundly changing treatment approaches in the
metastatic and adjuvant settings. One promising approach, highlighted in this
review, uses the inherent capacity of Salmonella to colonize and eliminate solid
tumors.
PMID- 28420040
TI - Semi-end-to-end esophagojejunostomy after laparoscopy-assisted total gastrectomy
better reduces stricture and leakage than the conventional end-to-side procedure:
A retrospective study.
AB - BACKGROUND AND OBJECTIVE: Laparoscopy-assisted total gastrectomy (LATG) has not
gained popularity due to the technical difficulty of esophagojejunostomy (EJ) and
the high incidence of EJ-related complications. Herein, we compared two types of
EJ for Roux-en-Y reconstruction to determine whether semi-end-to-end (SETE) EJ is
more convenient than the end-to-side (ETS) procedure and is capable of reducing
stricture and leakage. METHODS: A total of 268 patients who underwent LATG with
Roux-en-Y reconstruction were included in this study. Two types of EJ were
applied for LATG: conventional ETS EJ and SETE EJ. The surgical outcomes and
postoperative complications were compared. RESULTS: The mean reconstruction time
in the SETE group was shorter than that in the ETS group (41.6 +/- 8.0 min vs
51.3 +/- 9.2 min, P = 0.000). The incidences of total EJ-related complications,
EJ leakage, and EJ stricture in the SETE group and ETS group were 1.1% (1/92) and
10.2% (18/176), 1.1% (1/92) and 4.0% (7/176), and 0 and 6.2% (11/176),
respectively. The incidence of total EJ-related complications in the SETE group
was lower than that of the ETS group (P = 0.006), and the incidence of EJ
stricture in the SETE group was lower than that of the ETS group (P = 0.034).
CONCLUSIONS: SETE EJ is more convenient than the conventional ETS procedure and
is associated with a shorter reconstruction time and a lower incidence of EJ
stricture and leakage.
PMID- 28420041
TI - [18 F]Nifene test-retest reproducibility in first-in-human imaging of
alpha4beta2* nicotinic acetylcholine receptors.
AB - : The aim of this study was to examine the suitability of [18 F]nifene, a novel
alpha4beta2* nicotinic acetylcholine receptor (nAChR) radiotracer, for in vivo
brain imaging in a first-in-human study. METHODS: Eight healthy subjects (4 M,4
F;21-69,44 +/- 21 yrs) underwent a [18 F]nifene positron emission tomography scan
(200 +/- 3.7 MBq), and seven underwent a second scan within 58 +/- 31 days.
Regional estimates of DVR were measured using the multilinear reference tissue
model (MRTM2) with the corpus callosum as reference region. DVR reproducibility
was evaluated with test-retest variability (TRV) and intraclass correlation
coefficient (ICC). RESULTS: The DVR ranged from 1.3 to 2.5 across brain regions
with a TRV of 0-7%, and did not demonstrate a systematic difference between test
and retest. The ICCs ranged from 0.2 to 0.9. DVR estimates were stable after 40
min. CONCLUSION: The binding profile and tracer kinetics of [18 F]nifene make it
a promising alpha4beta2* nAChR radiotracer for scientific research in humans,
with reliable DVR test-retest reproducibility.
PMID- 28420042
TI - Determination of reference intervals of acid-base parameters in clinically
healthy dogs.
AB - OBJECTIVE: To establish reference intervals for traditionally- and Stewart's
approach-determined acid-base parameters in a population of clinically healthy
dogs. DESIGN: Prospective study (June 2011-September 2012). SETTING: Veterinary
teaching hospital. ANIMALS: Two hundred twenty-four client-owned, clinically
healthy dogs. INTERVENTIONS: Blood was collected from the jugular vein and the
dorsal pedal artery. MEASUREMENTS AND MAIN RESULTS: In the whole blood samples,
pH, PCO2 , and PO2 were measured and HCO3- , standard and total bicarbonate, base
excess, oxygen content, and alveolar-arterial oxygen differences were calculated.
Plasma sodium, potassium, chloride, calcium, albumin, and lactate concentrations
were measured and the following parameters were calculated separately for venous
and arterial samples: anion gap, anion gap corrected for albumin and phosphate,
sodium chloride difference and ratio, chloride gap, strong ion difference, strong
ion gap, and unmeasured anions. CONCLUSION: Reference intervals for traditionally
and Stewart's approach-determined acid-base parameters were established for
venous and arterial blood in dogs.
PMID- 28420043
TI - [Alcohol consumption prevalence in civil servants].
AB - : Temporomandibular dysfunction syndrome (TMDS) includes a number of clinical
conditions involving the temporomandibular joint (TMJ), the muscles involved in
mastication, or both. The symptoms of TMDS include decreased mobility,
masticatory muscle pain, TMJ pain, functional alteration accompanied by articular
noises, myofascial pain or deviation of the mouth opening. Work with visual
display terminals (VDTs) has become widespread in the past several years and the
conditions associated with this type of work have been associated with the
appearance of certain musculoskeletal pathologies. Our objective was to conduct a
review of the scientific literature onthe possible association between TMDS and
work with VDTs. METHOD: A search of the literature in MEDLINE (PubMed), Cochrane
Plus Library, CINHAL, Scielo and Google Academic was performed.We included those
studies involving workers using VDTs and the outcome measures had to include
references to TMDS symptoms. RESULTS AND DISCUSSION: A total of 112 articles were
identified, of which finally 11 were selected for in-depth review. Given the
heterogeneity of the results and the nature of the studies, we conclude that
currently there is insufficient evidence to support a consistent relationship
between TMDS pathology and work with VDTs. There is insufficient evidence linking
the presence of TMDS with ergonomic and postural aspects, an association that
should not be totally ruled out from a pathophysiological point of view and
biological plausibility. Further studies are needed to better assess this
relationship.
PMID- 28420044
TI - Role of MMP-7 in the pathogenesis of systemic lupus erythematosus (SLE).
AB - Systemic lupus erythematosus (SLE) is a clinically heterogeneous chronic,
inflammatory autoimmune disorder. The association of MMP-7 and disease severity
is still unclear. A total of 150 SLE patients and matched healthy controls were
recruited for this study. Disease activity was scored according to SLEDAI (98
active and 52 inactive disease). Mean serum MMP-7 levels were significantly
higher in SLE patients than controls ( p < 0.001). Patients with active disease
showed higher levels (16.24 +/- 6.2 ng/ml) as against inactive disease (10.50 +/-
3.97 ng/ml) ( p <= 0.0001). Mean MMP-7 mRNA expression was significantly higher
in patients (RQ = 3.16 +/- 0.93) as compared to controls (RQ = 2.21 +/- 0.89, p =
0.006). A positive correlation between MMP-7 levels, mRNA expression and SLEDAI
score was observed ( r = 0.563, r = 0.427). The MMP-7 -181 G allele was found to
be significantly higher among SLE patients ( p < 0.0001). A significant
association was noted between MMP-7 -181 A/G +G/G genotypes with renal ( p =
0.0027) and CNS ( p = 0.0031) manifestations and anti-dsDNA autoantibodies ( p =
0.0312). Serum MMP-7 levels and mRNA expression were elevated in advanced stages
of SLE, indicating that MMP-7 is associated with disease activity in SLE.
PMID- 28420045
TI - Drug-induced lupus erythematosus mimicking lymphoma on 18F-FDG-PET/CT.
PMID- 28420046
TI - Anti-heparan sulfate antibody and functional loss of glomerular heparan sulfate
proteoglycans in lupus nephritis.
AB - Background The purpose of this study was to evaluate the features of heparan
sulfate proteoglycans (HSPGs) as agrins of the glomerular basement membrane (GBM)
and circulating anti-heparan sulfate (HS) antibodies in lupus nephritis,
comparing titers among the following groups: lupus nephritis (LN), non-renal
lupus, non-lupus nephritis, and healthy controls. Methods The stage of nephritis
was determined based on the kidney biopsy. Alcian blue staining and
immunohistochemical (IHC) staining for agrin were performed for histological
evaluation of GBM HSPGs in normal glomeruli, non-lupus membranous
glomerulonephritis (MGN), and lupus MGN. The results were used for measurement of
the serum anti-HS antibody titers using an enzyme-linked immunosorbent assay
(ELISA) in the following groups: 38 healthy controls, 38 non-lupus nephritis, 37
non-renal lupus, and 38 LN. Results Glomerulus HSPGs were stained bluish-green
along the GBM with Alcian blue. However, IHC staining against agrin was almost
completely negative in the lupus MGN group compared with the normal and non-lupus
MGN groups, which showed brown staining of GBM. A higher level of anti-HS IgG was
detected in LN compared with other groups, respectively. Higher titers were
associated with the presence of SLE and nephritis. A higher degree of proteinuria
normalized to glomerular filtration rate (eGFR) was observed in association with
higher anti-HS antibody titers in LN. Conclusion This study demonstrated a
functional loss of GBM HSPGs and higher levels of circulating anti-HS antibodies
as a characteristic feature of lupus nephritis, suggesting their involvement in
the pathogenesis of lupus nephritis and proteinuria.
PMID- 28420047
TI - Organ damage accrual and distribution in systemic lupus erythematosus patients
followed-up for more than 10 years.
AB - Objective The aim of this study was to determine the prevalence, predictors and
progression of organ damage in a monocentric cohort of systemic lupus
erythematosus patients with a long follow-up. Organ damage was assessed by the
Systemic Lupus International Collaborating Clinics Damage Index one year after
diagnosis and every five years. Disease activity was measured by the systemic
lupus erythematosus disease activity index (SLEDAI)-2K at the beginning of the
follow-up. Univariate and multivariable analyses were used to detect items
associated with damage. A total of 511 systemic lupus erythematosus patients (92%
females, 95% Caucasian), prospectively followed from 1972 to 2014, were included.
Results After a mean disease duration of 16 years (SD: 9.5) and a mean follow-up
of 12.9 years (SD: 8.8), 354 patients (69.3%) had accrued some damage: 49.7%
developed mild/moderate damage, while 19.5% showed severe damage. Damage was
evident in 40% of 511 patients one year after diagnosis, and its prevalence
linearly increased over time. Longer disease duration, higher SLEDAI, severe
Raynaud's, chronic alopecia and cerebral ischaemia were significantly associated
with organ damage. No associations between damage and autoantibodies, including
anti-dsDNA, anti-Sm or antiphospholipid antibodies, were observed. Anyway,
antiphospholipid syndrome and anticardiolipin antibodies predicted the
development of neuropsychiatric damage. The ocular, musculoskeletal and
neuropsychiatric systems were the most frequently damaged organs, with a linear
increase during follow-up. Conclusion A high rate of moderate and severe damage
has been detected early in a wide cohort of young lupus patients, with a linear
trend of increase over time. Disease activity and long duration of disease
predict damage, while antiphospholipid antibodies play a role in determining
neuropsychiatric damage.
PMID- 28420048
TI - Pincer nail in a lupus patient.
AB - Pincer nail is a transverse overcurvature of the nail plate that may appear in
association with a variable number of diseases. We present a case report of a 28
year-old woman with pincer nail deformity associated with systemic lupus
erythematosus. A renal biopsy confirmed class V lupus nephritis and treatment had
included systemic steroids and cyclophosphamide. After 6 months there was a
marked improvement of nail deformities.
PMID- 28420049
TI - The spectrum of neuropsychiatric lupus in a Black Caribbean population: a report
of the Barbados National Lupus Registry.
AB - Objective The objective of this study was to examine neuropsychiatric lupus in a
Black Caribbean population. Methods We reviewed Barbados National Lupus Registry
patients with >=4 American College of Rheumatology criteria and a diagnosis of
neuropsychiatric lupus using the American College of Rheumatology 19 case
definitions. Results From 366 patients with four or more American College of
Rheumatology criteria for systemic lupus erythematosus, 55 (15%) had evidence of
neuropsychiatric lupus. There were 51 females and four males (F:M = 13:1) with a
median age of 31 years. A total of 76.4% had a single neuropsychiatric lupus
complication and 23.6% had two or three complications occurring sequentially or
concurrently. The top three complications were psychosis - 49.1% (95% CI 35.8,
62.5); ischaemic stroke - 32.7% (21.4, 46.5); and generalized tonic-clonic
seizures - 12.7% (6.0, 24.8). Twelve of the American College of Rheumatology 19
neuropsychiatric syndromes were represented: 91.2% central; 8.8% peripheral.
There were 521 observation years, and for 32 patients (58%) neuropsychiatric
lupus was a presenting feature. For the remaining 23 (42%) the first
neuropsychiatric lupus event came after systemic lupus erythematosus diagnosis -
median time of two years. Of the 22 deaths, systemic lupus erythematosus
nephritis caused almost half (45.5%) at a median age of 32. The prevalence of
nephritis was lower in the neuropsychiatric lupus subgroup (25.5%) compared with
the Barbados National Lupus Registry data (47%) ( P = 0.01). Ischaemic stroke
caused 22.7% of deaths at a median age of 46 and was the main cause of chronic
neurologic deficits amongst survivors. Conclusion Neuropsychiatric lupus was an
early cause of morbidity in systemic lupus erythematosus with predominantly
singular central nervous system complications, the most common of which was
psychosis. Most deaths occurred at a young age, principally from systemic lupus
erythematosus nephritis. Ischaemic stroke was the main neurologic cause of death
and disability.
PMID- 28420050
TI - Carotid intima-media thickness and arterial stiffness in pediatric systemic lupus
erythematosus.
AB - Objectives The carotid intima-media thickness (CIMT) and carotid arterial
stiffness index (CASI) act as the surrogate markers of atherosclerosis. We aim to
assess CIMT and CASI in pediatric systemic lupus erythematosus (SLE). Methods
Patients <= 20 years old fulfilling diagnostic criteria for SLE were enrolled.
Patients with active smoking, coronary heart disease, cerebrovascular disease,
arterial thrombosis, family history of hypercholesterolemia, chronic liver
disease, or other chronic severe diseases were excluded. The patients were
categorized into four groups: active SLE, age- and sex-matched control (control
A), inactive SLE, and age- and sex-matched control (control I), according to the
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). All subjects
underwent ultrasound of carotid arteries to evaluate CIMT and CASI. Results One
hundred and two SLE patients (26 active and 76 inactive) and one hundred and
three healthy controls (26 control A and 77 control I) were enrolled. The median
CIMT in all groups were not significantly different (0.43, 0.41-0.44; 0.43, 0.41
0.44; 0.42, 0.41-0.43; and 0.42, 0.41-0.43 mm, respectively).The CASI in active
SLE (13.5, 11.4-17.3) was significantly higher than in control A (8.2, 7.2-9.2) (
p < 0.0001), whereas CASI in inactive SLE (12.7, 10.9-15.7) was significantly
higher than in control I (8.9, 7.6-9.8). However, the CASI in active and inactive
SLE was not significantly different. Conclusions The higher CASI in active and
inactive pediatric SLE, implying functional change of carotid arteries, may be
early evidence of increased atherosclerosis in pediatric SLE. This functional
dysfunction has been found both in inactive and active SLE.
PMID- 28420051
TI - Circulating prolactin level in systemic lupus erythematosus and its correlation
with disease activity: a meta-analysis.
AB - Objective This study aimed to evaluate the relationship between circulating
prolactin level and systemic lupus erythematosus (SLE), and to establish a
correlation between plasma/serum prolactin levels and SLE activity. Methods We
performed a meta-analysis comparing the plasma/serum prolactin levels in patients
with SLE to controls, and examined correlation coefficients between circulating
prolactin level and SLE disease activity. Results Twenty-five studies with a
total of 1056 SLE patients and 426 controls were included. Prolactin levels were
significantly higher overall in the SLE group than in the control group
(standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 * 10
5). Stratification by ethnicity showed significantly elevated prolactin levels in
the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95%
CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD =
1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European
population. Subgroup analysis by sample size showed significantly higher
prolactin levels in the SLE group by small ( n < 30) and large sample numbers ( n
> 30). Meta-analysis of correlation coefficients showed a significantly positive
correlation between circulating prolactin level and SLE activity (correlation
coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 * 10-9). Circulating prolactin
levels were positively associated with SLE activity in European, Asian, and mixed
populations (SMD = 0.532, 95% CI = 0.443-0.609 p < 1.0 * 10-8; SMD = 0.427, 95%
CI = 0.240-0.583, p = 2.4 * 10-5; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 * 10
5, respectively). Conclusions Our meta-analysis demonstrated that circulating
prolactin levels are higher in patients with SLE, and that a significantly
positive correlation exists between prolactin levels and SLE activity.
PMID- 28420052
TI - Lupus nephritis in the Western Cape, a high prevalence area: an experience over
three decades.
AB - Background Systemic lupus erythematosus is a multisystem disease with serious
complications, including lupus nephritis. Systemic lupus erythematosus is
prevalent in the Western Cape, predominantly affecting women in the prime of
their lives. Renal biopsy is an important tool for the management of the lupus
patient with kidney disease, guiding treatment and assessing prognosis. Aims The
aim of this study was to ascertain if there has been a change in the spectrum of
renal pathology, patient characteristics and long-term outcomes in patients with
lupus nephritis in our region over three decades. Methods We reviewed 315 records
of systemic lupus erythematosus patients with suspected renal disease who
underwent renal biopsy in the Renal Unit at Tygerberg Hospital over three decades
between January 1983 and December 2012. Results Lupus nephritis consistently
affected young women. Class IV lupus nephritis remained the most common pattern
throughout the three decades. The overall five-year survival for this cohort was
67% (95% confidence interval (CI), 60-72%). Conclusion Class IV lupus nephritis
remained the most frequent class in our cohort of patients with the poorest
survival rates compared to other classes. The prognosis of lupus nephritis in our
region is considerably worse than that reported elsewhere in the world.
PMID- 28420053
TI - Risk of infective endocarditis in patients with systemic lupus erythematosus in
Taiwan: a nationwide population-based study.
AB - Objectives Patients with systemic lupus erythematosus are considered vulnerable
to infective endocarditis and prophylactic antibiotics are recommended before an
invasive dental procedure. However, the evidence is insufficient. This nationwide
population-based study evaluated the risk and related factors of infective
endocarditis in systemic lupus erythematosus. Methods We identified 12,102
systemic lupus erythematosus patients from the National Health Insurance research
oriented database, and compared the incidence rate of infective endocarditis with
that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable
proportional hazards model was employed to evaluate the risk of infective
endocarditis in the systemic lupus erythematosus cohort. Results After a mean
follow-up of more than six years, the systemic lupus erythematosus cohort had a
significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per
100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the
control cohort. By contrast, the older systemic lupus erythematosus cohort had
lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years
systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox
multivariate proportional hazards analysis revealed heart disease (hazard ratio =
5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034),
receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001),
and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001)
were independent risk factors for infective endocarditis in systemic lupus
erythematosus patients. Conclusions A higher risk of infective endocarditis was
observed in systemic lupus erythematosus patients. Risk factors for infective
endocarditis in the systemic lupus erythematosus cohort included heart disease,
chronic kidney disease, steroid pulse therapy within 30 days, and a recent
invasive dental procedure within 30 days.
PMID- 28420054
TI - The prevalence and determinants of anti-DFS70 autoantibodies in an international
inception cohort of systemic lupus erythematosus patients.
AB - Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the
diagnosis of SLE when they occur in the absence of other SLE-related
autoantibodies. This study is the first to report the prevalence of anti-DFS70 in
an early, multinational inception SLE cohort and examine demographic, clinical,
and autoantibody associations. Patients were enrolled in the Systemic Lupus
International Collaborating Clinics (SLICC) inception cohort within 15 months of
diagnosis. The association between anti-DFS70 and multiple parameters in 1137
patients was assessed using univariate and multivariate logistic regression. The
frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6
1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with
musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti
beta2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients
with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI:
0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence
of anti-DFS70 was higher than the range previously published for adult SLE (7.1
versus 0-2.8%) and was associated with musculoskeletal activity and anti-beta2
glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies
were rare (1.1%) and therefore may be helpful to discriminate between ANA
positive healthy individuals and SLE.
PMID- 28420055
TI - Perceived stress and reported cognitive symptoms among Georgia patients with
systemic lupus erythematosus.
AB - Objective To examine associations of perceived stress with cognitive symptoms
among adults with systemic lupus erythematosus (SLE). Methods Among 777 adult
(>=18 years) SLE patients, the association of Perceived Stress Scale (PSS) scores
with two self-reported cognitive symptoms was examined: forgetfulness
(severe/moderate vs. mild/none; from the Systemic Lupus Activity Questionnaire)
and difficulty concentrating (all/most vs. some/little/none of the time; from the
Lupus Impact Tracker). The study used multivariable logistic regression to
estimate the odds ratios (ORs) per minimal important difference (MID = 0.5*SD) of
PSS score and cognitive symptoms. Results Forgetfulness and difficulty
concentrating were reported by 41.7% and 29.5%, respectively. Women and those
with less education and high disease activity had higher PSS scores and were more
likely to report cognitive symptoms than their counterparts. With adjustment for
age, race, sex, education, and disease activity, each MID increase in PSS score
was associated with higher prevalence of forgetfulness (OR = 1.43, 95% CI 1.29
1.47) and difficulty concentrating (OR = 2.19, 95% CI 1.90-2.52). No substantial
differences in this association by age, race, sex, or disease activity were
noted. Conclusions SLE patients, particularly those with high disease activity,
report a high burden of cognitive symptoms, for which stress may be a modifiable
risk factor.
PMID- 28420056
TI - Treatment with belimumab in systemic lupus erythematosus does not impair antibody
response to 13-valent pneumococcal conjugate vaccine.
AB - Background/purpose The objective of this study was to explore the impact of
systemic lupus erythematosus and belimumab given in addition to standard of care
therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods
Forty-seven systemic lupus erythematosus patients and 21 healthy controls were
immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty
systemic lupus erythematosus patients were treated with traditional disease
modifying anti rheumatic drugs, 11 of those received belimumab in addition, and
32 patients were treated with concomitant prednisolone. Quantification of
serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was
performed in serum taken before and four to six weeks after vaccination using
multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F
and 6B were also analyzed using standard enzyme-linked immunosorbent assays.
Opsonophagocytic assay was performed on serotype 23F to evaluate the
functionality of the antibodies. Pre- and post-vaccination log transformed
antibody levels were compared to determine the impact of systemic lupus
erythematosus diagnosis and different treatments on antibody response. Results
Systemic lupus erythematosus patients as a group showed lower post-vaccination
antibody levels and lower fold increase of antibody levels after vaccination
compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus
erythematosus patients treated with belimumab in addition to standard of care
therapy or with only hydroxychloroquine did not differ compared to controls,
whereas the other treatment groups had significantly lower fold increase of post
vaccination antibody levels. Higher age was associated with lower post
vaccination antibody levels among systemic lupus erythematosus patients.
Conclusion Belimumab given in addition to traditional disease-modifying anti
rheumatic drugs or prednisolone did not further impair antibody response to 13
valent conjugated pneumococcal vaccine.
PMID- 28420057
TI - Central nervous system vasculitis in systemic lupus erythematosus: a case series
report in a tertiary referral centre.
AB - Central nervous system (CNS) vasculitis (CNS) in systemic erythematosus lupus
(SLE) is a rare and challenging diagnosis. We report four cases of CNS vasculitis
that occurred 5 to 16 years after the diagnosis of SLE. Magnetic resonance
imaging (MRI) detected different features suggestive of CNS vasculitis:
enhancement and thickening of the vascular wall, vascular stenosis, ischemic
brain lesions and intracerebral haemorrhage unlikely to correspond to other mimic
aetiologies. Three patients received combination therapy with glucocorticoids
(GC) and cyclophosphamide (CYC). Intravenous human immunoglobulin (IVIG) was
administered when the patient had a past history of serious adverse event to CYC
or high infectious risk. All patients showed imagiological improvement, at least
partially, 5 to 23 days after starting treatment. We discuss the management of
CNS in SLE including the role of magnetic resonance imaging (MRI).
PMID- 28420058
TI - Clinico-pathological features of repeat renal biopsies in patients with lupus
nephritis at Groote Schuur Hospital, Cape Town.
AB - Background Repeat renal biopsies in patients with lupus nephritis are usually
done to guide treatment or to establish disease chronicity. Their value is not
clear from available literature. There are also no available data in Africa to
guide clinicians. Methods This was a retrospective study of patients undergoing a
repeat renal biopsy between January 2003 and December 2014 from a single centre
in Cape Town, South Africa. Relevant demographic, clinical and histological
records of patients with repeat renal biopsies were documented. Comparison of
data from first and second renal biopsy was performed. Results Forty-four
patients had at least two biopsies done during the study period. Most patients
were females (81.8%). The mean biopsy interval was 2.8 +/- 1.8 (range 0.38-9.4)
years. Proteinuria was the main indication for the repeat biopsy (36.1%). The
glomerular filtration rate and proteinuria worsened between the two biopsies ( p
= 0.001 and 0.019, respectively) suggesting disease progression. Most patients
(65.4%) with a non-proliferative class of lupus nephritis at first biopsy
progressed into a proliferative class, whereas patients with initial
proliferative lupus nephritis at first biopsy (77.8%) remained as proliferative
at repeat biopsy. Treatment was changed in 85% of patients at second biopsy.
Conclusion Repeat renal biopsies in patients with lupus nephritis presents a
useful means of assessing disease progression and provides guidance regarding
modification of treatment. More studies are, however, required to evaluate the
value of repeat biopsies and perhaps the need for protocol renal biopsies in
patients with lupus nephritis.
PMID- 28420059
TI - Neuropsychiatric symptoms in systemic lupus erythematosus: impact on quality of
life.
AB - Objective Assess quality of life in patients with systemic lupus erythematosus
(SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE).
Methods Quality of life was assessed using the Short-Form 36 item Health Survey
(SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow
up. SF-36 subscales and summary scores were calculated and compared with quality
of life of the general Dutch population and patients with other chronic diseases.
Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98
had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom
64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a
significantly reduced quality of life in all subscales of the SF-36. Quality of
life at follow-up showed a significant improvement in physical functioning role (
p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health
( p = 0.014) and mental component score ( p = 0.042) in patients with
neuropsychiatric symptoms not attributed to SLE, but no significant improvement
was seen in patients with NPSLE. Conclusion Quality of life is significantly
reduced in patients with SLE presenting neuropsychiatric symptoms compared with
the general population and patients with other chronic diseases. Quality of life
remains considerably impaired at follow-up. Our results illustrate the need for
biopsychosocial care in patients with SLE and neuropsychiatric symptoms.
PMID- 28420060
TI - Risk factors to predict the development of chronic kidney disease in patients
with lupus nephritis.
AB - Objectives We analyzed the clinical follow-up results of 88 lupus nephritis
patients to find prognostic factors for the development of chronic kidney disease
in ethnically homogeneous Korean patients with biopsy-proven lupus nephritis.
Methods Sociodemographic, clinical, laboratory, and treatment-related data at the
time of kidney biopsy and during follow-up were obtained. Renal biopsy specimens
were reclassified according to the International Society of Pathology/Renal
Pathology Society classification, separately, by two renal pathologists blinded
to the previous classification. Univariate and multivariate analyses were
performed using the Cox proportional hazard regression model to identify
independent risk factors for chronic kidney disease in lupus nephritis patients.
Results Eighteen of 88 patients (20.5%) developed chronic kidney disease during a
mean follow-up of 47.6 months (range: 12-96 months). Patients who developed
chronic kidney disease were older at onset of lupus nephritis, had less
education, and were more likely to have hypertension; they had lower serum
albumin levels, lower platelet levels, higher serum creatinine levels, lower
estimated glomerular filtration rate, higher chronicity index, and lower
frequency of anti-ribosomal P antibodies, and they were less likely to be in
complete remission in the first year. In stepwise multivariable analyses,
hypertension, lower glomerular filtration rate, and failure to achieve complete
remission in the first year of treatment were significant predictors of the
development of chronic kidney disease in lupus nephritis patients. Conclusions
These findings suggest that patients with hypertension and decreased kidney
function at the onset of lupus nephritis and showing a poor response to
immunosuppressive drugs in the first year should be monitored carefully and
managed aggressively to avoid deterioration of kidney function.
PMID- 28420061
TI - Metabolic profiling reveals new serum biomarkers of lupus nephritis.
AB - Metabolomics has been applied to explore altered metabolite profiles in disease
and identify unique metabolic signatures specific to certain pathologies. The aim
of the current study is to characterize the metabolic profile of patients
diagnosed with lupus nephritis (LN) and explore new insights into underlying
disease processes. A metabolomic approach using ultra-high-performance liquid
chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) was
developed in serum samples from 32 LN patients, 30 idiopathic nephrotic syndrome
(INS) patients and 28 healthy controls (HCs). Potential biomarkers were screened
from orthogonal projection to latent structures discriminate analysis (OPLS-DA)
and further evaluated by receiver operating characteristic analysis (ROC). A
total of 14 potential biomarkers were screened and tentatively identified for LN
patients compared to HCs. Compared to HCs and INS patients, the LN patients had
increased serum levels of sorbitol and glycocholic acid metabolites and decreased
levels of cortisol, creatinine and L-aspartyl-L-phenylalanine. A panel of three
metabolomics (theophylline, oxidized glutathione and capric acid) was identified
as biomarkers of LN with a sensitivity of 87.50% and a specificity of 67.86%
using ROC analysis. Our results suggest that UPLC-HRMS based quantification of
circulating metabolites was a useful tool for identification of biomarkers with
the ability to segregate LN patients from INS patients and HCs. The potential
biomarkers indicated that the LN metabolic disturbance may be closely associated
with inflammation injury, oxidative stress and phospholipid metabolism.
PMID- 28420062
TI - Intravenous immunoglobulin: a biological corticosteroid-sparing agent in some
autoimmune conditions.
AB - Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of
autoimmune and systemic inflammatory diseases. This compound is effective in a
wide range of clinical conditions other than primary immunodeficiency, including
autoimmune diseases, inflammatory disorders, infections, organ transplantation,
and possibly supportive therapy for cancer. Systemic corticosteroids remain the
gold standard treatment for many autoimmune diseases, but their long-term use is
associated with complications in diverse organs and systems. Osteoporosis,
osteonecrosis, cardiovascular disease, infections, and cancer have been
associated with this treatment. Therefore, physicians are occasionally forced to
withdraw the treatment with steroids. Biological agents may represent a good
alternative, but in addition to being very expensive, these agents may have
serious side effects. This review aimed to cover the major advances in the use of
IVIg as a steroid-sparing agent in some relevant autoimmune diseases.
PMID- 28420063
TI - Patients' experiences of lupus-related foot problems: a qualitative
investigation.
AB - Background Systemic lupus erythematosus (SLE) can present with a variety of
symptoms. Previous research has shown there is a high prevalence of lower limb
and foot problems in patients with SLE associated with the musculoskeletal,
vascular and neurological changes. Furthermore, there is a high prevalence of
infections affecting the feet and a range of common skin and nail problems.
However, it is not known how these foot problems impact upon people's lives.
Therefore, we aimed to explore this using a qualitative approach. Method
Following ethical approval, 12 participants were recruited who had a diagnosis of
SLE, current and/or past experience of foot problems and were over 18 years in
age. Following consent, interviews were carried out with an interpretivist
phenomenological approach to both data collection and analysis. Results Seven
themes provide insight into: foot problems and symptoms; the impact of these foot
problems and symptoms on activities; disclosure and diagnosis of foot problems;
treatment of foot problems and symptoms; perceived barriers to professional
footcare; unanswered questions about feet and footcare; and identification of the
need for professional footcare and footcare advice. Conclusion These participants
tend to "self-treat" rather than disclose that they may need professional
footcare. A lack of focus upon foot health within a medical consultation is
attributed to the participant's belief that it is not within the doctor's role,
even though it is noted to contribute to reduced daily activity. There is a need
for feet to be included as a part of patient monitoring and for foot health
management to be made accessible for people with SLE.
PMID- 28420064
TI - Anti-topoisomerase-I antibodies in systemic lupus erythematosus and potential
association with the presence of anti-dsDNA antibodies.
PMID- 28420065
TI - A five consecutive years' study of renal function outcome among biopsy proven
lupus nephritis patients in Southern Iran.
AB - Introduction Lupus nephritis (LN) is one of the most common complications of
systemic lupus erythematous (SLE) responsible for an increase in mortality and
morbidity. This study was conducted to evaluate the outcome for LN patients and
factors that correlate with their outcome. Materials and methods We included 80
patients with proved LN and more than three-years follow up at Shiraz University
of Medical Sciences. We prepared a data gathering sheet for each patient and
extracted the data from patients' file records which existed in the hospital.
Results The mean age of patients was 36.6 +/- 10.6 years, and 88.3% of patients
were women. Men develop remission less than women (three men (33.3%) vs 49 women
(72.1%), p = 0.014). Chronic kidney disease (GFR < 60) developed in 14.2% of our
patients, and 7.8% progressed to end stage renal disease (ESRD). We found a
significant relation between initial creatinine (Cr), GFR, and urine 24 hour
protein with developing ESRD ( p = 0.002, 0.039, < 0.001, respectively). Also we
found that hypertensive patients are at risk of developing ESRD 0.4 times more
than normotensive patients ( p = 0.047, CI: 0.131-0.985). Lack of remission was
significantly associated with ESRD progression ( p = 0.025). Conclusion There is
a strong agreement among studies that initial Cr, hypertension and lack of
remission are associated with poor outcome in LN patients. As a result we must
observe hypertensive patients and patients with increased Cr more carefully.
Also, we should consider changing treatment in patients who do not develop
remission. In spite of dominancy of women in SLE, men are likely to have poorer
outcomes.
PMID- 28420066
TI - Disease evolution in late-onset and early-onset systemic lupus erythematosus.
AB - Objective The objective of this study was to compare clinical features, disease
activity, and outcome in late-onset versus early-onset systemic lupus
erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970
were followed prospectively according to standard protocol and tracked on a
computerized database. Patients entering the cohort within one year of diagnosis
constitute the inception cohort. Patients with late-onset (age at diagnosis >=50)
disease were identified and matched 1:2 based on gender and first clinic visit
(+/-5) years with patients with early-onset disease (age at diagnosis 18-40
years). Results A total of 86 patients with late-onset disease (84.9% female,
81.4% Caucasian, mean age at SLE diagnosis +/- SD 58.05 +/- 7.30) and 169
patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE
diagnosis +/- SD 27.80 +/- 5.90) were identified. At enrollment, late-onset SLE
patients had a lower total number of American College of Rheumatology (ACR)
criteria, with less renal and neurologic manifestations. Mean SLE Disease
Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially
renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores
decreased in both groups, while mean Systemic Lupus International Collaborating
Clinics/ACR Damage Index (SDI) scores increased more significantly in the late
onset group; they developed more cardiovascular, renal, and ocular damage, and
had higher prevalence of cardiovascular risk factors. Conclusion Although the
late-onset SLE group had a milder presentation and less active disease, with the
evolution of disease, they developed more organ damage likely as a consequence of
cardiovascular risk factors and aging.
PMID- 28420067
TI - Kidney transplantation for end-stage renal disease in lupus nephritis, a very
safe procedure: a single Latin American transplant center experience.
AB - Background Lupus nephritis (LN) is one of the most frequent complications of SLE
and occurs in up to 50% of cases depending on the studied population. Of these,
approximately 20% progress to end-stage renal disease (ESRD), with the treatment
of choice being a kidney transplant. Objective The objective of this study was to
describe the clinical outcome of patients transplanted due to LN, compared with
patients transplanted for other causes, in a Latin American population from the
Fundacion Valle del Lili in Cali, Colombia. Methods Observational, retrospective
case study with controls matched by age, sex and type of donor in a single center
between 1996 and 2014. Results Sixty-five kidney transplants were performed in
patients with LN and ESRD. The survival of patients with LN was 98% at 1, 10 and
15 years ( p = .99). For controls by age and sex, survival was also 98% at 15
years post-transplant, and for controls by donor, the survival rate was 100% at 5
years and 98% at 15 years. Graft survival in patients with LN to 1, 5 and 15
years was 92%, 83% and 71%, respectively; for controls by age and sex, it was
90%, 84% and 64%, respectively, and for the controls by donor, it was 89%, 86%
and 79%, respectively ( p = .7718). There were no statistically significant
differences found in the cumulative incidence of acute graft rejection in the
first year, but it was found that acute rejection is a factor that relates to the
loss of function of the renal graft ( p = .032). Of the patients transplanted for
LN, two (3.1%) experienced a recurrence of the disease. One patient died after a
diagnosis of recurrence of LN due to an infection. Conclusions Kidney
transplantation is a good option for patients with ESRD due to LN. In this
Hispanic population, the survival of patients, graft survival, and cumulative
incidence of graft rejection are not different from those of other transplanted
patients. In addition, recurrence of LN was rare, showing the benefits of renal
transplantation in LN patients with ESRD.
PMID- 28420068
TI - Pentraxin-3 levels are associated with vasculitis and disease activity in
childhood-onset systemic lupus erythematosus.
AB - Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic
autoimmune disease characterized by inflammatory organ damage by means of
vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory
processes, predominantly from endothelial cells. In adult studies, PTX3 has shown
to be an indicator of active vasculitis both in large-vessel and small-vessel
vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated
with disease activity, and with some of the clinical manifestations and
laboratory parameters. We aimed to ascertain if PTX3 might be a significant
mediator in cSLE and if it might indicate active vasculitis during the course of
the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and
41 healthy subjects. We have investigated its relation with disease activity,
damage, clinical features, laboratory parameters and medications. Results Serum
levels of PTX3 were found to be increased in cSLE compared to healthy controls
(mean +/- SD; 10.6 +/- 8.2 ng/mL vs 2.7 +/- 1.3 ng/mL, p < 0.001). PTX3
concentrations were also in correlation with SLEDAI-2K ( r = 0.57, p < 0.001).
When viewed from the clinical perspective, serum PTX3 levels were significantly
higher only in patients with active vasculitis ( p < 0.001), Raynaud phenomenon (
p = 0.006) and mucocutaneous manifestations ( p < 0.001). However, an association
between PTX3 and age, age at disease onset, disease duration, complement levels,
PedSDI score (pediatric version of the Systemic Lupus International Collaborating
Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin
levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected.
Conclusions Patients with cSLE have increased levels of serum PTX3 compared to
healthy controls. Thus, serum PTX-3 level might be a significant mediator in
cSLE. Apart from these, the results support that PTX3 reflects active cutaneous
vasculitis in cSLE and correlates with disease activity.
PMID- 28420069
TI - Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance
and disease activity in systemic lupus erythematosus: a cross-sectional human
study.
AB - Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has
recently been involved in the pathogenesis of autoimmune diseases. To assess
whether LL-37 reflects disease activity, we measured serum levels of it in
systemic lupus erythematosus (SLE) patients with active and inactive disease
compared to healthy controls. LL-37 was also compared between new and old cases.
Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was
measured. Methods The study population consisted of 50 SLE patients and 28
healthy controls. Of those, 39 patients had active and 11 patients had inactive
disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special
method. Results There was no difference in levels of LL-37 between patients and
healthy controls (50.9 +/- 20.8 vs. 67.7 +/- 43.3 ng/ml, P = 0.31). LL-37 did not
correlate with SLEDAI and its items in total patients. LL-37 had a positive
correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active
patients (78% of patients), multivariate regression analysis showed significant
negative correlation between LL-37 and C3 ( P = 0.01, standardized beta -0.50).
No difference was found in levels of PAB between patients and controls (90.4 +/-
34.1 vs. 86.9 +/- 25.6 HK, P = 0.4).There was no difference in the levels of PAB
between patients with active and inactive disease (93.2 +/- 34.1 vs. 80.2 +/-
33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI
items and total score. However, a positive correlation between the levels of LL
37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on
this study, serum LL-37 and PAB did not increase in lupus compared with healthy
individuals. LL-37 serum values rose in parallel with SLEDAI in active disease.
Positive correlation between serum PAB and LL-37 could be a great achievement of
this study that may suggest the role of antioxidants in controlling NETosis.
PMID- 28420070
TI - Lower kidney allograft survival in African-Americans compared to Hispanic
Americans with lupus.
AB - Background and objective African-Americans and Hispanic-Americans with lupus are
the two most common minority groups who receive kidney transplants in the USA. It
is unknown if African-Americans and Hispanic-Americans with lupus have similar
outcomes after kidney transplantation. In this study, we assessed whether African
Americans compared to Hispanic-Americans have worse kidney allograft survival
after risk factors of rejection and other prognostic factors were matched between
both groups. Methods Out of 1816 African-Americans and 901 Hispanic-Americans
with lupus, who received kidney transplants between 1987 and 2006 and had
complete records in the UNOS program, 478 pairs were matched in 16 baseline
predictors and follow-up time employing a predicted probability of group
membership. The primary outcome was kidney allograft survival. Main secondary
outcomes were rejection, allograft failure attributed to rejection, and
mortality. Results Matched pairs were predominantly women (81%) with the mean age
of 36 years. 96% were on dialysis before transplantation. 89% of recipients
received kidneys from deceased donors and 15.5% from expanded criteria donors.
12% of recipients had zero HLA mismatch. African-Americans compared to Hispanic
Americans had lower cumulative allograft survival during 12-year follow-up ( p <
0.001). African-Americans compared to Hispanic-Americans had higher rates of
rejection (10.4 vs 6.73 events/100 patients-years; p = 0.0002) and allograft
failure attributed to rejection (6.31 vs 3.99; p = 0.0023). However, African
Americans and Hispanic-Americans had similar mortality rates (2.71 vs 2.31; p =
0.4269). Conclusions African-Americans compared to Hispanic-Americans with lupus
had lower kidney allograft survival when recognized risk factors of rejection
were matched between groups.
PMID- 28420071
TI - Pleuropulmonary involvement in patients with systemic lupus erythematosus from a
Latin American inception cohort (GLADEL).
AB - Objectives The objectives of this study were to examine the demographic and
clinical features associated with the occurrence of pleuropulmonary
manifestations, the predictive factors of their occurrence and their impact on
mortality in systemic lupus erythematosus (SLE) patients. Materials and methods
The association of pleuropulmonary manifestations with demographic and clinical
features, the predictive factors of their occurrence and their impact on
mortality were examined in GLADEL patients by appropriate univariable and
multivariable analyses. Results At least one pleuropulmonary manifestation
occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most
frequent (24.0%). Age at SLE onset >=30 years (OR 1.42; 95% CI 1.10-1.83), the
presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non
ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR
3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58;
95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were
associated with pleuropulmonary manifestations, whereas cutaneous manifestations
were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart
disease (HR 2.24; 95% CI 1.63-3.09), SDI scores >=1 (OR 1.54; 95% CI 1.10-2.17)
and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently
predicted their subsequent occurrence. Cutaneous manifestations were protective
of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI
0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased
survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations
are frequent in SLE, particularly pleuritis. Older age, respiratory tract
infection, cardiac, systemic and renal involvement were associated with them,
whereas cutaneous manifestations were negatively associated. Cardiac compromise,
SDI scores >=1 and anti-La positivity at disease onset were predictive of their
subsequent occurrence, whereas cutaneous manifestations were protective. They
independently contributed to a decreased survival in these patients.
PMID- 28420072
TI - Reduction of nitric oxide and DNA/RNA oxidation products are associated with
active disease in systemic lupus erythematosus patients.
AB - The aims of the present study were to evaluate biomarkers of oxidative and
nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular
products of DNA/RNA oxidative damage and their correlation with disease activity.
This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI
< 6) and 50 with active SLE (SLEDAI >= 6) without renal impairment. Oxidative
stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence,
advanced oxidation protein products (AOPP), total radical-trapping antioxidant
parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products.
Patients with SLE showed increased oxidative stress, as demonstrated by the
augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and
reduced total antioxidant capacity ( p < 0.0001), without differences between
patients with active disease and in remission. NOx levels and DNA/RNA oxidation
products were inversely and independently associated with disease activity ( p <
0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The
linear regression analysis showed that about 5% of the SLEDAI score can be
explained by the levels of DNA/RNA oxidation products ( r2:0.051; p = 0.002) and
about 9% of this score by the levels of NOx ( r2:0.091; p < 0.0001). This study
provides evidence for an inverse association between serum NOx levels and DNA/RNA
oxidation products and SLE disease activity, suggesting that
oxidative/nitrosative stress markers may be useful in evaluating SLE disease
activity and progression of the disease.
PMID- 28420073
TI - Future Prospects for the Development of Cost-Effective Adenovirus Vaccines.
AB - Vaccination is one of the most efficient tools for disease prevention, and a
continuously growing field of research. However, despite progress, we still need
more efficient and cost-effective vaccines that would improve access to those in
need. In this review, we will describe the status of virus-vectored vaccine
technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines
have proven to be efficient in military vaccinations against Ad4 and Ad7 and as
highly efficient vectored vaccines against rabies. The question of how other
adenovirus-based vaccines can become as efficient as the rabies vaccine is the
underlying theme in this review. Here, we will first give an overview of the
basic properties of vectored vaccines, followed by an introduction to the
characteristics of adenoviral vectors and previously tested modifications of the
vector backbone and expression cassettes, with a focus on how they can contribute
to increased vaccine cost-effectiveness. Finally, we will highlight a few
successful examples of research that have attempted to improve the use of
adenoviral-based vaccines by improving the transgene immunogenicity.
PMID- 28420074
TI - Natural Pathogen Control Chemistry to Replace Toxic Treatment of Microbes and
Biofilm in Cooling Towers.
AB - Application of toxic antibacterial agents is considered necessary to control
prevalent fresh water microorganisms that grow in evaporative cooling water
systems, but can adversely affect the environment and human health. However,
natural antibacterial water chemistry has been applied in industrial cooling
water systems for over 10 years to inhibit microorganisms with excellent results.
The water chemistry method concentrates natural minerals in highly-softened water
to produce elevated pH and dissolved solids, while maintaining low calcium and
magnesium content. The method provides further benefits in water conservation,
and generates a small volume of non-toxic natural salt concentrate for cost
efficient separation and disposal if required. This report describes the
antimicrobial effects of these chemistry modifications in the cooling water
environment and the resultant collective inhibition of microbes, biofilm, and
pathogen growth. This article also presents a novel perspective of parasitic
microbiome functional relationships, including "Trojan Protozoans" and biofilms,
and the function of polyvalent metal ions in the formation and inhibition of
biofilms. Reducing global dependence on toxic antibacterial agents discharged to
the environment is an emerging concern due to their impact on the natural
microbiome, plants, animals and humans. Concurrently, scientists have concluded
that discharge of antibacterial agents plays a key role in development of
pathogen resistance to antimicrobials as well as antibiotics. Use of natural
antibacterial chemistry can play a key role in managing the cooling water
environment in a more ecologically sustainable manner.
PMID- 28420075
TI - Application of Hydrogen Peroxide as an Innovative Method of Treatment for
Legionella Control in a Hospital Water Network.
AB - OBJECTIVES: To evaluate the effectiveness of hydrogen peroxide (HP) use as a
disinfectant in the hospital water network for the control of Legionella spp.
colonization. METHODS: Following the detection of high levels of Legionella
contamination in a 136-bed general hospital water network, an HP treatment of the
hot water supply (25 mg/L) was adopted. During a period of 34 months, the
effectiveness of HP on Legionella colonization was assessed. Legionella was
isolated in accordance with ISO-11731 and identification was carried out by
sequencing of the mip gene. RESULTS: Before HP treatment, L. pneumophila sg 2-15
was isolated in all sites with a mean count of 9950 +/- 8279 cfu/L. After one
month of HP treatment, we observed the disappearance of L. pneumophila 2-15,
however other Legionella species previously not seen were found;
Legionellapneumophila 1 was isolated in one out of four sampling sites (2000
cfu/L) and other non-pneumophila species were present in all sites (mean load
3000 +/- 2887 cfu/L). Starting from September 2013, HP treatment was modified by
adding food-grade polyphosphates, and in the following months, we observed a
progressive reduction of the mean load of all species (p < 0.05), resulting in
substantial disappearance of Legionella colonization. CONCLUSION: Hydrogen
peroxide demonstrated good efficacy in controlling Legionella. Although in the
initial phases of treatment it appeared unable to eliminate all Legionella
species, by maintaining HP levels at 25 mg/L and adding food-grade
polyphosphates, a progressive and complete control of colonization was obtained.
PMID- 28420076
TI - Mitochondrial Genomes Provide Insights into the Phylogeny of Lauxanioidea
(Diptera: Cyclorrhapha).
AB - The superfamily Lauxanioidea is a significant dipteran clade including over 2500
known species in three families: Lauxaniidae, Celyphidae and Chamaemyiidae. We
sequenced the first five (three complete and two partial) lauxanioid
mitochondrial (mt) genomes, and used them to reconstruct the phylogeny of this
group. The lauxanioid mt genomes are typical of the Diptera, containing all 37
genes usually present in bilaterian animals. A total of three conserved
intergenic sequences have been reported across the Cyclorrhapha. The inferred
secondary structure of 22 tRNAs suggested five substitution patterns among the
Cyclorrhapha. The control region in the Lauxanioidea has apparently evolved very
fast, but four conserved structural elements were detected in all three complete
mt genome sequences. Phylogenetic relationships based on the mt genome data were
inferred by Maximum Likelihood and Bayesian methods. The traditional
relationships between families within the Lauxanioidea, (Chamaemyiidae +
(Lauxaniidae + Celyphidae)), were corroborated; however, the higher-level
relationships between cyclorrhaphan superfamilies are mostly poorly supported.
PMID- 28420077
TI - Recognition of the Duration and Prediction of Insect Prevalence of Stored Rough
Rice Infested by the Red Flour Beetle (Tribolium castaneum Herbst) Using an
Electronic Nose.
AB - The purpose of this research is to explore the feasibility of applying an
electronic nose for the intelligent monitoring of injurious insects in a stored
grain environment. In this study, we employed an electronic nose to sample rough
rice that contained three degrees of red flour beetle (Tribolium castaneum
Herbst) infestation for different durations-light degree (LD), middle degree
(MD), and heavy degree (HD)-and manually investigated the insect situation at the
same time. Manual insect situation investigation shows that, in all three rice
treatments, the insect amounts gradually decreased after infestation. When the
insect population of stored rough rice was under 13 insects per 60 g of rough
rice, the natural speed of decrease of the insect population became very slow and
reached the best artificial insect killing period. Linear discriminant analysis
(LDA) provided good performance for MD and HD insect harm duration
identification, but performed poorly for LD insect harm duration identification.
Both k-means clustering analysis (K-means) and fuzzy c-means analysis (FCM)
effectively identified the insect harm duration for stored rough rice. The
results from the back-propagation artificial neural network (BPNN) insect
prevalence prediction for the three degrees of rough rice infestation
demonstrated that the electronic nose could effectively predict insect prevalence
in stored grain (fitting coefficients were larger than 0.89). The predictive
ability was best for LD, second best for MD, and least accurate for HD. This
experiment demonstrates the feasibility of electronic noses for detecting both
the duration and prevalence of an insect infestation in stored grain and provides
a reference for the intelligent monitoring of an insect infestation in stored
grains.
PMID- 28420078
TI - Natural Phenol Polymers: Recent Advances in Food and Health Applications.
AB - Natural phenol polymers are widely represented in nature and include a variety of
classes including tannins and lignins as the most prominent. Largely consumed
foods are rich sources of phenol polymers, notably black foods traditionally used
in East Asia, but other non-edible, easily accessible sources, e.g., seaweeds and
wood, have been considered with increasing interest together with waste materials
from agro-based industries, primarily grape pomace and other byproducts of fruit
and coffee processing. Not in all cases were the main structural components of
these materials identified because of their highly heterogeneous nature. The
great beneficial effects of natural phenol-based polymers on human health and
their potential in improving the quality of food were largely explored, and this
review critically addresses the most interesting and innovative reports in the
field of nutrition and biomedicine that have appeared in the last five years.
Several in vivo human and animal trials supported the proposed use of these
materials as food supplements and for amelioration of the health and production
of livestock. Biocompatible and stable functional polymers prepared by peroxidase
catalyzed polymerization of natural phenols, as well as natural phenol polymers
were exploited as conventional and green plastic additives in smart packaging and
food-spoilage prevention applications. The potential of natural phenol polymers
in regenerative biomedicine as additives of biomaterials to promote growth and
differentiation of osteoblasts is also discussed.
PMID- 28420079
TI - How Hyperarousal and Sleep Reactivity Are Represented in Different Adult Age
Groups: Results from a Large Cohort Study on Insomnia.
AB - Hyperarousal is a 24-h state of elevated cognitive and physiological activation,
and is a core feature of insomnia. The extent to which sleep quality is affected
by stressful events-so-called sleep reactivity-is a vulnerability factor for
developing insomnia. Given the increasing prevalence of insomnia with age, we
aimed to investigate how hyperarousal and sleep reactivity were related to
insomnia severity in different adult age groups. Data were derived from a large
cohort study investigating the natural history of insomnia in a population-based
sample (n = 1693). Baseline data of the Arousal Predisposition Scale (APS) and
Ford Insomnia Response to Stress Test (FIRST) were examined across age and
sleep/insomnia subgroups: 25-35 (n = 448), 35-45 (n = 528), and 45-55 year olds
(n = 717); good sleepers (n = 931), individuals with insomnia symptoms (n = 450),
and individuals with an insomnia syndrome (n = 312). Results from factorial
analyses of variance (ANOVA) showed that APS scores decreased with increasing
age, but increased with more severe sleep problems. FIRST scores were not
significantly different across age groups, but showed the same strong increase as
a function of sleep problem severity. The findings indicate that though arousal
predisposition and sleep reactivity increase with more severe sleep problems,
only arousal decreases with age. How arousing events affect an individual during
daytime thus decreases with age, but how this arousal disrupts sleep is
equivalent across different adult age groups. The main implication of these
findings is that treatment of insomnia could be adapted for different age groups
and take into consideration vulnerability factors such as hyperarousal and stress
reactivity.
PMID- 28420080
TI - Delineating the Common Biological Pathways Perturbed by ASD's Genetic Etiology:
Lessons from Network-Based Studies.
AB - In recent decades it has become clear that Autism Spectrum Disorder (ASD)
possesses a diverse and heterogeneous genetic etiology. Aberrations in hundreds
of genes have been associated with ASD so far, which include both rare and common
variations. While one may expect that these genes converge on specific common
molecular pathways, which drive the development of the core ASD characteristics,
the task of elucidating these common molecular pathways has been proven to be
challenging. Several studies have combined genetic analysis with bioinformatical
techniques to uncover molecular mechanisms that are specifically targeted by
autism-associated genetic aberrations. Recently, several analysis have suggested
that particular signaling mechanisms, including the Wnt and Ca2+/Calmodulin
signaling pathways are often targeted by autism-associated mutations. In this
review, we discuss several studies that determine specific molecular pathways
affected by autism-associated mutations, and then discuss more in-depth into the
biological roles of a few of these pathways, and how they may be involved in the
development of ASD. Considering that these pathways may be targeted by specific
pharmacological intervention, they may prove to be important therapeutic targets
for the treatment of ASD.
PMID- 28420081
TI - Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and
Response to Tumor Necrosis Factor (TNF) Inhibitors.
AB - The term spondyloarthritis (SpA) is used to describe a group of multifactorial
chronic inflammatory diseases characterized by a predisposing genetic background
and clinical manifestations typically involving the sacroiliac joint. The absence
of pathognomonic clinical and/or laboratory findings generally results in a delay
in diagnosis and, consequently, in treatment. In addition, 20-40% of SpA patients
are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given
these considerations, it is important to identify biomarkers that can facilitate
the diagnosis and assessment of disease activity. As inflammation plays a key
role in the pathogenesis of SpA, inflammatory mediators have been investigated as
potential biomarkers for diagnosing the disease and predicting response to
therapy. Some investigators have focused their attention on the role of matrix
metalloproteinases (MMPs), which are known to be markers of synovial inflammation
that is generated in the joint in reaction to inflammatory stimuli. Several
studies have been carried out to verify if serum MMPs levels could be useful to
diagnose SpA, to assess disease severity, and to predict response to TNF
inhibitor therapy. The current review focuses on MMPs' role in SpA pathogenesis,
diagnosis and therapeutic implications.
PMID- 28420082
TI - Can Early Rehabilitation Prevent Posttraumatic Osteoarthritis in the
Patellofemoral Joint after Anterior Cruciate Ligament Rupture? Understanding the
Pathological Features.
AB - Knee instability resulting from anterior cruciate ligament (ACL) rupture is a
high-risk factor for posttraumatic osteoarthritis (PTOA) in the patellofemoral
joint (PFJ). However, whether non-weight-bearing and weight-bearing treatments
have chondroprotective effects remains unclear. Twenty-four adult New Zealand
White male rabbits were employed in this study. All animals received ACL
transection in the right knee and sham surgery in the left knee. The rabbits were
randomly assigned to the following groups: (I) In the sedentary (SED) group, the
rabbits (n = 6) were simply kept in their cage; (II) In the continuous passive
motion (CPM) group, the rabbits (n = 6) performed CPM exercise for 7 days,
starting from the first postoperative day; (III) In the active treadmill exercise
(TRE) group, the rabbits (n = 6) performed TRE for 2 weeks; (IV) In the CPM + TRE
group, the rabbits (n = 6) executed CPM exercise, followed by TRE. Two joint
surfaces (the retropatella and femoral trochlear groove) were assessed at 4 weeks
after operation. Although the gross appearance in each group was comparable,
histological examination revealed significant differences in the articular
cartilage status. The CPM group exhibited a greater thickness of articular
cartilage, maintenance of tidemark continuity, abundant glycosaminoglycan (GAG),
and significantly lower inflammatory cytokine 9, e.g., tumor necrosis factor
alpha (TNF-alpha) 0 levels, with modest cell apoptosis (i.e., caspase-3). By
contrast, the TRE group displayed the worst pathological features: an irregular
cartilage surface and chondrocyte disorganization, reduced cartilage thickness,
breakdown of the tidemark, depletion of collagen fibers, loss of GAG, and the
highest levels of TNF-alpha and caspase-3 expression. Furthermore, the CPM + TRE
group had more favorable outcomes than the SED group, indicating that suitable
exercise is needed. The sham treatment displayed no variance in the changes in
the two joint surfaces among groups. These data indicate that the application of
early CPM rehabilitation is suggested for subjects in order to decrease the risk
of PTOA without ACL reconstruction in the PFJ compartment in rabbits. The early
TRE program, however, had harmful outcomes. Additionally, inactivity was
discovered to initiate the development of PTOA.
PMID- 28420083
TI - A Theoretical Study and Numerical Simulation of a Quasi-Distributed Sensor Based
on the Low-Finesse Fabry-Perot Interferometer: Frequency-Division Multiplexing.
AB - The application of the sensor optical fibers in the areas of scientific
instrumentation and industrial instrumentation is very attractive due to its
numerous advantages. In the industry of civil engineering for example, quasi
distributed sensors made with optical fiber are used for reliable strain and
temperature measurements. Here, a quasi-distributed sensor in the frequency
domain is discussed. The sensor consists of a series of low-finesse Fabry-Perot
interferometers where each Fabry-Perot interferometer acts as a local sensor.
Fabry-Perot interferometers are formed by pairs of identical low reflective Bragg
gratings imprinted in a single mode fiber. All interferometer sensors have
different cavity length, provoking frequency-domain multiplexing. The optical
signal represents the superposition of all interference patterns which can be
decomposed using the Fourier transform. The frequency spectrum was analyzed and
sensor's properties were defined. Following that, a quasi-distributed sensor was
numerically simulated. Our sensor simulation considers sensor properties, signal
processing, noise system, and instrumentation. The numerical results show the
behavior of resolution vs. signal-to-noise ratio. From our results, the Fabry
Perot sensor has high resolution and low resolution. Both resolutions are
conceivable because the Fourier Domain Phase Analysis (FDPA) algorithm elaborates
two evaluations of Bragg wavelength shift.
PMID- 28420084
TI - Assessment of the Occupational Health and Food Safety Risks Associated with the
Traditional Slaughter and Consumption of Goats in Gauteng, South Africa.
AB - BACKGROUND: This study assessed the occupational health and food safety risks
associated with the traditional slaughter of goats and the consumption of such
meat in Tshwane, South Africa. METHODS: A convenience sample of 105 respondents
agreed to be interviewed using structured questionnaires. RESULTS: A high
proportion (62.64%) of practitioners admitted to not wearing protective clothing
during slaughter. Slaughtering was mainly carried out by males (99%) with
experience (62.2%). Forty-four percent of practitioners only changed the clothes
they wore while slaughtering when they got home. During the actual slaughter, up
to seven people may be involved. The majority (58.9%) of slaughters occurred
early in the morning and none of the goats were stunned first. In 77.5% of cases,
the health status of the persons who performed the slaughtering was not known.
The majority (57.3%) of the slaughters were performed on a corrugated iron roof
sheet (zinc plate). In 83.3% of the cases, the carcass was hung up to facilitate
bleeding, flaying, and evisceration. Meat inspection was not practiced by any of
the respondents. Throughout the slaughter process, the majority used the same
knife (84.3) and 84.7% only cleaned the knife when it became soiled. A total of
52.0% of the respondents processed the carcass and cooked the meat immediately.
The majority (80.0%) consumed the meat within 30 min of cooking. CONCLUSIONS: Men
are at a higher risk of occupational health hazards associated with traditional
slaughter, which can be transferred to their households. Unhygienic methods of
processing and the lack of any form of post-mortem examination increase the risk
of food-borne illness following the consumption of such meat.
PMID- 28420085
TI - Electrochemical Detection of Dopamine Using 3D Porous Graphene Oxide/Gold
Nanoparticle Composites.
AB - The detection of dopamine in a highly sensitive and selective manner is crucial
for the early diagnosis of a number of neurological diseases/disorders. Here, a
report on a new platform for the electrochemical detection of dopamine with a
considerable accuracy that comprises a 3D porous graphene oxide (pGO)/gold
nanoparticle (GNP)/pGO composite-modified indium tin oxide (ITO) is presented.
The pGO was first synthesized and purified by ultrasonication and centrifugation,
and it was then further functionalized on the surface of a GNP-immobilized ITO
electrode. Remarkably, owing to the synergistic effects of the pGO and GNPs, the
3D pGO-GNP-pGO-modified ITO electrode showed a superior dopamine-detection
performance compared with the other pGO- or GNP-modified ITO electrodes. The
linear range of the newly developed sensing platform is from 0.1 MUM to 30 MUM
with a limit of detection (LOD) of 1.28 MUM, which is more precise than the other
previously reported GO-functionalized electrodes. Moreover, the 3D pGO-GNP-pGO
modified ITO electrodes maintained their detection capability even in the
presence of several interfering molecules (e.g., ascorbic acid, glucose). The
proposed platform of the 3D pGO-GNP-pGO-modified ITO electrode could therefore
serve as a competent candidate for the development of a dopamine-sensing platform
that is potentially applicable for the early diagnosis of various neurological
diseases/disorders.
PMID- 28420086
TI - Blockwise PPG Enhancement Based on Time-Variant Zero-Phase Harmonic Notch
Filtering.
AB - So far, many approaches have been developed for motion artifact (MA) reduction
from photoplethysmogram (PPG). Specifically, single-input MA reduction methods
are useful to apply wearable and mobile healthcare systems because of their low
hardware costs and simplicity. However, most of them are insufficiently developed
to be used in real-world situations, and they suffer from a phase distortion
problem. In this study, we propose a novel single-input MA reduction algorithm
based on time-variant forward-backward harmonic notch filtering. To verify the
proposed method, we collected real PPG data corrupted by MA and compared it with
existing single-input MA reduction methods. In conclusion, the proposed zero
phase line enhancer (ZLE) was found to be superior for MA reduction and exhibited
zero phase response.
PMID- 28420088
TI - Range Analysis of Thermal Stress and Optimal Design for Tungsten-Rhenium Thin
Film Thermocouples Based on Ceramic Substrates.
AB - A thermal stress range analysis of tungsten-rhenium thin film thermocouples based
on ceramic substrates is presented to analyze the falling off and breakage
problems caused by the mismatch of the thermal stresses in thin film
thermocouples (TFTCs) and substrate, and nano-indentation experiments are done to
measure and calculate the film stress to compare with the simulation results.
Optimal design and fabrication of tungsten-rhenium TFTCs based on ceramic
substrates is reported. Static high temperature tests are carried out, which show
the optimization design can effectively reduce the damage caused by the thermal
stress mismatch.
PMID- 28420087
TI - Skeletal Muscle Nucleo-Mitochondrial Crosstalk in Obesity and Type 2 Diabetes.
AB - Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation
and accumulation of fatty acid intermediates in the form of long and medium chain
acylcarnitines, may contribute to ectopic lipid deposition and insulin resistance
during high fat diet (HFD)-induced obesity. The present review discusses the
roles of anterograde and retrograde communication in nucleo-mitochondrial
crosstalk that determines skeletal muscle mitochondrial adaptations, specifically
alterations in mitochondrial number and function in relation to obesity and
insulin resistance. Special emphasis is placed on the effects of high fat diet
(HFD) feeding on expression of nuclear-encoded mitochondrial genes (NEMGs)
nuclear receptor factor 1 (NRF-1) and 2 (NRF-2) and peroxisome proliferator
receptor gamma coactivator 1 alpha (PGC-1alpha) in the onset and progression of
insulin resistance during obesity and how HFD-induced alterations in NEMG
expression affect skeletal muscle mitochondrial adaptations in relation to beta
oxidation of fatty acids. Finally, the potential ability of acylcarnitines or
fatty acid intermediates resulting from mitochondrial beta oxidation to act as
retrograde signals in nucleo-mitochondrial crosstalk is reviewed and discussed.
PMID- 28420089
TI - Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating
Thermogenesis.
AB - Ghrelin, an orexigenic hormone released primarily from the gut, signals the
hypothalamus to stimulate growth hormone release, enhance appetite and promote
weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS
R), is highly expressed in the brain, with highest expression in Agouti-Related
Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron
specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice
by activating non-shivering thermogenesis. To further decipher the specific
neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP
neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f). Our data showed that GHS
R in AgRP neurons is required for ghrelin's stimulatory effects on growth hormone
secretion, acute food intake and adiposity, but not for long-term total food
intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced
obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The
HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced
thermogenic activation in both brown and subcutaneous fat; this implies that GHS
R suppression in AgRP neurons enhances sympathetic outflow. In summary, our
results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis,
and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing
energy utilization and pathogenesis of DIO.
PMID- 28420090
TI - Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific
Endoribonuclease Activity.
AB - Protein translation is the most common target of toxin-antitoxin system (TA)
toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific
manner, thereby blocking translation. While past studies mainly focused on the
digestion of mRNA, recent analysis revealed that toxins can also digest tRNA,
rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA
containing recognition sequences in the absence of ribosome in vitro. However,
increasing evidence suggests that in vivo digestion may occur in association with
ribosomes. Despite the prevalence of recognition sequences in many mRNA,
preferential digestion seems to occur at specific positions within mRNA and also
in certain reading frames. In this review, a variety of tools utilized to study
the nuclease activities of toxins over the past 15 years will be reviewed. A
recent adaptation of an RNA-seq-based technique to analyze entire sets of
cellular RNA will be introduced with an emphasis on its strength in identifying
novel targets and redefining recognition sequences. The differences in
biochemical properties and postulated physiological roles will also be discussed.
PMID- 28420091
TI - Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts:
Emerging Mechanisms of Disease.
AB - The rapid increase in metabolic diseases, which occurred in the last three
decades in both industrialized and developing countries, has been related to the
rise in sugar-added foods and sweetened beverages consumption. An emerging topic
in the pathogenesis of metabolic diseases related to modern nutrition is the role
of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high
temperature processed foods, but also endogenously formed as a consequence of a
high dietary sugar intake. Animal models of high sugar consumption, in particular
fructose, have reported AGE accumulation in different tissues in association with
peripheral insulin resistance and lipid metabolism alterations. The in vitro
observation that fructose is one of the most rapid and effective glycating agents
when compared to other sugars has prompted the investigation of the in vivo
fructose-induced glycation. In particular, the widespread employment of fructose
as sweetener has been ascribed by many experimental and observational studies for
the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet
derived AGEs have been demonstrated to interfere with many cell functions such as
lipid synthesis, inflammation, antioxidant defences, and mitochondrial
metabolism. Moreover, emerging evidence also in humans suggest that this impact
of dietary AGEs on different signalling pathways can contribute to the onset of
organ damage in liver, skeletal and cardiac muscle, and the brain, affecting not
only metabolic control, but global health. Indeed, the most recent reports on the
effects of high sugar consumption and diet-derived AGEs on human health reviewed
here suggest the need to limit the dietary sources of AGEs, including added
sugars, to prevent the development of metabolic diseases and related
comorbidities.
PMID- 28420092
TI - Analysis of Sub-Lethal Toxicity of Perfluorooctane Sulfonate (PFOS) to Daphnia
magna Using 1H Nuclear Magnetic Resonance-Based Metabolomics.
AB - 1H nuclear magnetic resonance (NMR)-based metabolomics was used to characterize
the response of Daphnia magna after sub-lethal exposure to perfluorooctane
sulfonate (PFOS), a commonly found environmental pollutant in freshwater
ecosystems. Principal component analysis (PCA) scores plots showed significant
separation in the exposed samples relative to the controls. Partial least squares
(PLS) regression analysis revealed a strong linear correlation between the
overall metabolic response and PFOS exposure concentration. More detailed
analysis showed that the toxic mode of action is metabolite-specific with some
metabolites exhibiting a non-monotonic response with higher PFOS exposure
concentrations. Our study indicates that PFOS exposure disrupts various energy
metabolism pathways and also enhances protein degradation. Overall, we identified
several metabolites that are sensitive to PFOS exposure and may be used as
bioindicators of D. magna health. In addition, this study also highlights the
important utility of environmental metabolomic methods when attempting to
elucidate acute and sub-lethal pollutant stressors on keystone organisms such as
D. magna.
PMID- 28420093
TI - Potential Role of Free Fatty Acids in the Pathogenesis of Periodontitis and
Primary Sjogren's Syndrome.
AB - Clinical studies have shown that metabolic disorders such as type 2 diabetes and
dyslipidemia are associated with increased risk of oral-related diseases, such as
periodontitis and Sjogren's syndrome. Although changes in the immune system are
critical in both of these metabolic disorders and oral-related diseases, the
mechanism underlying the interaction between these diseases remains largely
unknown. Obesity and type 2 diabetes are known to be associated with higher
concentrations of free fatty acids in blood. Among free fatty acids, saturated
fatty acids such as palmitic acid have been demonstrated to induce inflammatory
responses mainly via the innate immune systems, and to be involved in the
pathogenesis of type 2 diabetes in tissues such as adipose tissue, liver,
pancreas, and skeletal muscle. Here, we highlight recent advances in evidence for
the potential involvement of palmitic acid in the pathogenesis of periodontitis
and Sjogren's syndrome, and discuss the possibility that improvement of the lipid
profile could be a new strategy for the treatment of these diseases.
PMID- 28420095
TI - Parenteral Nutrition and Lipids.
AB - Lipids have multiple physiological roles that are biologically vital. Soybean oil
lipid emulsions have been the mainstay of parenteral nutrition lipid formulations
for decades in North America. Utilizing intravenous lipid emulsions in parenteral
nutrition has minimized the dependence on dextrose as a major source of
nonprotein calories and prevents the clinical consequences of essential fatty
acid deficiency. Emerging literature has indicated that there are benefits to
utilizing alternative lipids such as olive/soy-based formulations, and
combination lipids such as soy/MCT/olive/fish oil, compared with soybean based
lipids, as they have less inflammatory properties, are immune modulating, have
higher antioxidant content, decrease risk of cholestasis, and improve clinical
outcomes in certain subgroups of patients. The objective of this article is to
review the history of IVLE, their composition, the different generations of
widely available IVLE, the variables to consider when selecting lipids, and the
complications of IVLE and how to minimize them.
PMID- 28420094
TI - Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and
Potential New Treatments.
AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver
disorders worldwide. It is associated with clinical states such as obesity,
insulin resistance, and type 2 diabetes, and covers a wide range of liver
changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH),
liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid
accumulation, insulin resistance, and inflammation, have been implicated in the
pathogenesis of NAFLD, but the underlying mechanisms, including those that drive
disease progression, are not fully understood. Both innate and recruited immune
cells mediate the development of insulin resistance and NASH. Therefore,
modifying the polarization of resident and recruited macrophage/Kupffer cells is
expected to lead to new therapeutic strategies in NAFLD. Oxidative stress is also
pivotal for the progression of NASH, which has generated interest in carotenoids
as potent micronutrient antioxidants in the treatment of NAFLD. In addition to
their antioxidative function, carotenoids regulate macrophage/Kupffer cell
polarization and thereby prevent NASH progression. In this review, we summarize
the molecular mechanisms involved in the pathogenesis of NAFLD, including
macrophage/Kupffer cell polarization, and disturbed hepatic function in NAFLD. We
also discuss dietary antioxidants, such as beta-cryptoxanthin and astaxanthin,
that may be effective in the prevention or treatment of NAFLD.
PMID- 28420096
TI - A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of
Traditional Hepatoprotective Chinese Herbal Medicines.
AB - Herbal medicines are widely used for treating liver diseases and generally
regarded as safe due to their extensive use in Traditional Chinese Medicine
practice for thousands of years. However, in recent years, there have been
increased concerns regarding the long-term risk of Herb-Induced Liver Injury
(HILI) in patients with liver dysfunction. Herein, two representative Chinese
herbal medicines: one-Xiao-Chai-Hu-Tang (XCHT)-a composite formula, and the other
Radix Polygoni Multiflori (Heshouwu)-a single herb, were analyzed by network
pharmacology study. Based on the network pharmacology framework, we exploited the
potential HILI effects of XCHT and Heshouwu by predicting the molecular
mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT
and Heshouwu. According to our network results, kaempferol and thymol in XCHT and
rhein in Heshouwu exhibit the largest number of liver injury target connections,
whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these
herbal medicines. This network pharmacology assay might serve as a useful tool to
explore the underlying molecular mechanism of HILI. Based on the theoretical
predictions, further experimental verification should be performed to validate
the accuracy of the predicted interactions between herbal ingredients and protein
targets in the future.
PMID- 28420097
TI - Synthesis of Curcuminoids and Evaluation of Their Cytotoxic and Antioxidant
Properties.
AB - Curcumin (1) and ten derivatives (2-11) were synthesized and evaluated as
cytotoxic and antioxidant agents. The results of primary screening by
Sulforhodamine B assay against five human cancer cell lines (U-251 MG,
glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human
chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us
to calculate the half maximal inhibitory concentration (IC50) values for the more
active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the
most active against both cell lines and were more active than curcumin itself.
Thiobarbituric acid reactive substances (TBARS) assay showed that 7 has potent
activity; even stronger than curcumin, alpha-tocopherol, and quercetin.
PMID- 28420098
TI - Development and Validation of a Questionnaire to Assess Knowledge, Threat and
Coping Appraisal, and Intention to Practice Healthy Behaviors Related to Non
Communicable Diseases in the Thai Population.
AB - Non-communicable diseases (NCDs) are important issues in Thailand and health
sectors are now focusing on modifiable risks that include cognitive, affective
and behavioral factors. This study aimed to develop and validate a questionnaire
to assess knowledge about NCDs, threat appraisal, coping appraisal and intention
to practice based on protection motivation theory. Content validity was
determined by the mean of the item content validity index (I-CVI) from five
experts. The questionnaire was pilot tested for difficulty of knowledge items and
reliability test using the Kuder-Richardson (KR)-20 and Cronbach's alpha
coefficient among 30 Thai adult subjects in the health office for two sub
districts. The mean I-CVI ranged from 0.90-1.00 and difficulty of knowledge
ranged from 0.3-0.9. The reliability test of knowledge by KR-20 ranged from 0.648
0.799, while Cronbach's alpha coefficients of threat and coping appraisal and
intention to practice ranged from 0.70-0.843. We compared sociodemographic data,
knowledge about NCDs, threat appraisal, coping appraisal and intention to
practice between 50 diabetic type 2 cases and 50 controls. T2DM cases had higher
age, knowledge scores on diabetes and hypertension, threat appraisal scores on
hypertension and cardiovascular disease when compared with control (p < 0.05).
The questionnaire was valid and sufficiently reliable to use for data collection.
PMID- 28420100
TI - Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf.
Caldora penicillata.
AB - A bioactivity guided study of a cf. Caldora penicillata species, collected during
a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a
commonwealth of the USA), led to the isolation of a new thiazoline-containing
alkaloid, laucysteinamide A (1). Laucysteinamide A is a new monomeric analogue of
the marine cyanobacterial metabolite, somocystinamide A (2), a disulfide-bonded
dimeric compound that was isolated previously from a Fijian marine
cyanobacterium. The structure and absolute configuration of laucysteinamide A (1)
was determined by a detailed analysis of its NMR, MS, and CD spectra. In
addition, the highly bioactive lipid, curacin D (3), was also found to be present
in this cyanobacterial extract. The latter compound was responsible for the
potent cytotoxicity of this extract to H-460 human non-small cell lung cancer
cells in vitro.
PMID- 28420101
TI - The Effect of Citrus Essential Oils and Their Constituents on Growth of
Xanthomonas citri subsp. citri.
AB - Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is
the most devastating of the citrus diseases worldwide. During our study, we found
that Essential oils (EOs) of some citrus cultivars are effective on Xcc.
Therefore, it prompted us to determine the plant metabolites responsible for the
antibacterial properties. We obtained EOs from some locally cultivated citrus by
using a Clevenger apparatus and their major constituents were identified by gas
chromatography/mass spectrometry (GC-MS). The effect of Citrus aurantium, C.
aurantifolia, Fortunella sp. EOs and their major constituents were evaluated
against Xcc-KVXCC1 using a disk diffusion assay. Minimal inhibitory and
bactericidal concentration of the EOs and their constituents were determined
using the broth microdilution method. C. aurantium, C. aurantifolia Eos, and
their major constituents including citral, linalool, citronellal, geraniol, alpha
terpineol, and linalyl acetate indicated antibacterial effects against Xcc. The
C. aurantifolia EO and citral showed the highest antibacterial activity among the
tested EOs and constituents with inhibition zones of 15 +/- 0.33 mm and 16.67 +/-
0.88 mm, respectively. Synergistic effects of the constituents were observed
between alpha-terpineol-citral, citral-citronellal, citral-geraniol, and
citronellal-geraniol by using a microdilution checkerboard assay. Transmission
electron microscopy revealed that exposure of Xcc cells to citral caused cell
wall damage and altered cytoplasmic density. We introduced C. aurantifolia and C.
aurantium EOs, and their constituents citral, alpha-terpineol, citronellal,
geraniol, and linalool as possible control agents for CBC.
PMID- 28420102
TI - Efficient Actor Recovery Paradigm for Wireless Sensor and Actor Networks.
AB - The actor nodes are the spine of wireless sensor and actor networks (WSANs) that
collaborate to perform a specific task in an unverified and uneven environment.
Thus, there is a possibility of high failure rate in such unfriendly scenarios
due to several factors such as power consumption of devices, electronic circuit
failure, software errors in nodes or physical impairment of the actor nodes and
inter-actor connectivity problem. Therefore, it is extremely important to
discover the failure of a cut-vertex actor and network-disjoint in order to
improve the Quality-of-Service (QoS). In this paper, we propose an Efficient
Actor Recovery (EAR) paradigm to guarantee the contention-free traffic-forwarding
capacity. The EAR paradigm consists of a Node Monitoring and Critical Node
Detection (NMCND) algorithm that monitors the activities of the nodes to
determine the critical node. In addition, it replaces the critical node with
backup node prior to complete node-failure which helps balancing the network
performance. The packets are handled using Network Integration and Message
Forwarding (NIMF) algorithm that determines the source of forwarding the packets;
either from actor or sensor. This decision-making capability of the algorithm
controls the packet forwarding rate to maintain the network for a longer time.
Furthermore, for handling the proper routing strategy, Priority-Based Routing for
Node Failure Avoidance (PRNFA) algorithm is deployed to decide the priority of
the packets to be forwarded based on the significance of information available in
the packet. To validate the effectiveness of the proposed EAR paradigm, the
proposed algorithms were tested using OMNET++ simulation.
PMID- 28420099
TI - Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids:
Facts and Artifacts.
AB - Na+,K+-ATPase is the only known receptor of cardiotonic steroids (CTS) whose
interaction with catalytic alpha-subunits leads to inhibition of this enzyme. As
predicted, CTS affect numerous cellular functions related to the maintenance of
the transmembrane gradient of monovalent cations, such as electrical membrane
potential, cell volume, transepithelial movement of salt and osmotically-obliged
water, symport of Na+ with inorganic phosphate, glucose, amino acids,
nucleotides, etc. During the last two decades, it was shown that side-by-side
with these canonical Na+i/K+i-dependent cellular responses, long-term exposure to
CTS affects transcription, translation, tight junction, cell adhesion and
exhibits tissue-specific impact on cell survival and death. It was also shown
that CTS trigger diverse signaling cascades via conformational transitions of the
Na+,K+-ATPase alpha-subunit that, in turn, results in the activation of membrane
associated non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase and
the inositol 1,4,5-triphosphate receptor. These findings allowed researchers to
propose that endogenous CTS might be considered as a novel class of steroid
hormones. We focus our review on the analysis of the relative impact Na+i,K+i
mediated and -independent pathways in cellular responses evoked by CTS.
PMID- 28420103
TI - Electrochemical Genosensing of Circulating Biomarkers.
AB - Management and prognosis of diseases requires the measurement in non- or
minimally invasively collected samples of specific circulating biomarkers,
consisting of any measurable or observable factors in patients that indicate
normal or disease-related biological processes or responses to therapy.
Therefore, on-site, fast and accurate determination of these low abundance
circulating biomarkers in scarcely treated body fluids is of great interest for
health monitoring and biological applications. In this field, electrochemical DNA
sensors (or genosensors) have demonstrated to be interesting alternatives to more
complex conventional strategies. Currently, electrochemical genosensors are
considered very promising analytical tools for this purpose due to their fast
response, low cost, high sensitivity, compatibility with microfabrication
technology and simple operation mode which makes them compatible with point-of
care (POC) testing. In this review, the relevance and current challenges of the
determination of circulating biomarkers related to relevant diseases (cancer,
bacterial and viral infections and neurodegenerative diseases) are briefly
discussed. An overview of the electrochemical nucleic acid-based strategies
developed in the last five years for this purpose is given to show to both
familiar and non-expert readers the great potential of these methodologies for
circulating biomarker determination. After highlighting the main features of the
reported electrochemical genosensing strategies through the critical discussion
of selected examples, a conclusions section points out the still existing
challenges and future directions in this field.
PMID- 28420104
TI - Low Power Near Field Communication Methods for RFID Applications of SIM Cards.
AB - Power consumption and communication distance have become crucial challenges for
SIM card RFID (radio frequency identification) applications. The combination of
long distance 2.45 GHz radio frequency (RF) technology and low power 2 kHz near
distance communication is a workable scheme. In this paper, an ultra-low
frequency 2 kHz near field communication (NFC) method suitable for SIM cards is
proposed and verified in silicon. The low frequency transmission model based on
electromagnetic induction is discussed. Different transmission modes are
introduced and compared, which show that the baseband transmit mode has a better
performance. The low-pass filter circuit and programmable gain amplifiers are
applied for noise reduction and signal amplitude amplification. Digital-to-analog
converters and comparators are used to judge the card approach and departure. A
novel differential Manchester decoder is proposed to deal with the internal clock
drift in range-controlled communication applications. The chip has been fully
implemented in 0.18 um complementary metal-oxide-semiconductor (CMOS) technology,
with a 330 uA work current and a 45 uA idle current. The low frequency chip can
be integrated into a radio frequency SIM card for near field RFID applications.
PMID- 28420105
TI - One-Year Results of a Synthetic Intervention Model for the Primary Prevention of
T2D among Elderly Individuals with Prediabetes in Rural China.
AB - Objective: The objective of this study was to evaluate the effectiveness of a
synthetic intervention model aimed at preventing type 2 diabetes and controlling
plasma glucose, body weight and waist circumference in elderly individuals with
prediabetes in rural China. Methods: We randomly assigned 434 (180 men and 254
women; mean age, 69 years; mean body mass index, 23.6 kg/m2) with prediabetes to
either the intervention group or the control group. Each participant in the
intervention group received synthetic intervention for 1 year. Results: The
incidence of diabetes was 4.2% in the intervention group, versus 19.7% in the
control group at the end of 1 year (p < 0.001). Compared with the control group,
the intervention group experienced a great decrease in fasting glucose (-3.9 vs.
2.2 mg/dL, p < 0.001), body weight (-3.2 vs. 1.7 kg, p < 0.001), waist
circumference (-2.4 vs. 1.0 cm, p < 0001), total cholesterol (-9.1 vs. -4.6
mg/dL. p = 0.014) and HbA1c (-1.0 vs. 0.1 mg %, p = 0.002) at the end of 1 year.
Conclusions: The incidence of diabetes of the control group was higher than that
of the intervention group. Besides, the synthetic intervention contributes to
weight loss and glucose decrease, and may be effective in reducing the risk of
diabetes among elderly individuals with prediabetes in rural China.
PMID- 28420106
TI - Temporary Black Henna Tattoos and Sensitization to para-Phenylenediamine (PPD):
Two Paediatric Case Reports and a Review of the Literature.
AB - Background: The use of temporary henna tattoos has increased dramatically in
recent years, especially in children and adolescents. To obtain a darker colour
and prolong the life of the tattoo, red henna, a plant-derived substance, is
typically added to para-phenylenediamine (PPD). The mixture is called temporary
black henna tattoo (TBHT). Because of its molecular characteristics, PPD can
induce skin sensitization that may cause various clinical manifestations with
successive exposures, among which the most common is allergic contact dermatitis
(ACD). This report describes two paediatric cases of PPD sensitization and ACD
after the exposure to TBHT and summarizes the literature on this emerging
clinical problem. Case Presentation: We describe two cases of childhood-onset ACD
that occurred 2 and 10 days, respectively, after the application of a TBHT during
the summer holidays. Patch tests showed an evident positive response to 1% PPD in
both cases. Sensitization to PPD occurred in the first case because a previous
henna tattoo did not result in overt symptoms; in the second case, the reaction
occurred after the same tattoo was retouched. In both cases, hypopigmentation
persisted and both the patients and their families were advised to avoid further
contact with PPD-containing materials and substances that could lead to cross
reactions. Conclusions: Sensitization to PPD is a growing phenomenon in children.
The most common cause appears to be exposure to TBHT in which PPD might be
present at unknown or high concentrations. Once sensitization occurs, patients
may experience severe clinical symptoms which can present with a persistent
hypopigmentation when they are re-exposed to substances that contain or cross
react with PPD. Given the widespread use of PPD, TBHT could adversely affect the
daily life of paediatric patients; thus, for this reason, this practice as a
fashion accessory must be discouraged. In addition, it is extremely important to
provide scientific information on the risks of TBHT to consumers, especially to
adolescents and to the parents of younger children to prevent PPD sensitization.
PMID- 28420107
TI - Prepartum Lying Behavior of Holstein Dairy Cows Housed on Pasture through
Parturition.
AB - Utilizing pasture-based systems may increase cow comfort during late gestation
and calving as it lacks the constraints of confinement housing. The objective of
this study was to quantify lying behavior and activity of Holstein dairy cows
housed on pasture during the 6 d before calving. Sixteen Holstein dairy cows were
moved to pasture 3 weeks before their projected calving date. Data loggers were
attached 14 d prior to projected calving date. Behavior was evaluated 6 d before
calving for all cows (n = 16) and 6 h prior to calving for a subset of cows (n =
6) with known calving times. Data loggers recorded at 1-min intervals to
determine lying time (h/d and %/h), lying bouts (n/d and n/h), lying bout
duration (min/bout), and steps (n/d and n/h). A repeated measures analysis of
variance with contrasts was performed to determine if lying behaviors and
activity differed between baseline and day or hour of interest. Lying time was
greater 6 d prior to calving compared to the day of and before calving. Cows had
longer lying bouts 6 d prior to calving compared to day of calving. Cows spent
less time lying in the hour before calving compared to 6 h prior to parturition.
The lack of change in behavior and activity during the 7 d prior to calving may
indicate that pasture provided an adequate environment for cows during the
prepartum period but did not impact cow welfare in the hours leading up to
calving.
PMID- 28420108
TI - A Robust Crowdsourcing-Based Indoor Localization System.
AB - WiFi fingerprinting-based indoor localization has been widely used due to its
simplicity and can be implemented on the smartphones. The major drawback of WiFi
fingerprinting is that the radio map construction is very labor-intensive and
time-consuming. Another drawback of WiFi fingerprinting is the Received Signal
Strength (RSS) variance problem, caused by environmental changes and device
diversity. RSS variance severely degrades the localization accuracy. In this
paper, we propose a robust crowdsourcing-based indoor localization system
(RCILS). RCILS can automatically construct the radio map using crowdsourcing data
collected by smartphones. RCILS abstracts the indoor map as the semantics graph
in which the edges are the possible user paths and the vertexes are the location
where users may take special activities. RCILS extracts the activity sequence
contained in the trajectories by activity detection and pedestrian dead
reckoning. Based on the semantics graph and activity sequence, crowdsourcing
trajectories can be located and a radio map is constructed based on the
localization results. For the RSS variance problem, RCILS uses the trajectory
fingerprint model for indoor localization. During online localization, RCILS
obtains an RSS sequence and realizes localization by matching the RSS sequence
with the radio map. To evaluate RCILS, we apply RCILS in an office building.
Experiment results demonstrate the efficiency and robustness of RCILS.
PMID- 28420109
TI - Comparison of Biogenic Amines and Mycotoxins in Alfalfa and Red Clover Fodder
Depending on Additives.
AB - In the production of fermented feed, each crop can be contaminated with a variety
of microorganisms that may produce natural pollutants. Biogenic amines,
mycotoxins, and undesirable organic acids can decrease health feed safety. The
aim of this study was to compare the counts of microorganisms, levels of biogenic
amines, and the mycotoxins in forage legumes, and also to compare the occurrence
of microorganisms and levels of mycotoxins in green fodder and subsequently
produced silage and the influence of additives on the content of natural harmful
substances in silage. The experimental plot was located in Troubsko and Vatin, in
the Czech Republic. Two varieties of Medicago sativa and one variety of Trifolium
pratense were compared. Green fodder and subsequently produced silage reaching up
to 23% of dry matter were evaluated and prepared using a bio-enzymatic additive
and a chemical additive. Green fodder of Medicago sativa was more contaminated by
Enterococci than Trifolium pratense fodder. The obvious difference was determined
by the quality of silage leachate. The silage prepared from Medicago sativa
fodder was more contaminated with butyric acid. Fungi were present in higher
counts in the anaerobic environment of green fodder and contaminated it with
zearalenone and deoxynivalenol. Lower counts of fungi were found in silage,
although the zearalenone content did not change. Lower content of deoxynivalenol
was detected in silage, compared with green fodder. Silages treated with a
chemical additive were found not to contain butyric acid. Lower ethanol content
was determined, and the tendency to reduce the risk of biogenic amines occurrence
was evident. The additives proved to have no influence on the content of
mycotoxins.
PMID- 28420110
TI - Chemical Sensors and Biosensors in Italy: A Review of the 2015 Literature.
AB - The contributions of Italian researchers to sensor research in 2015 is reviewed.
The analysis of the activities in one year allows one to obtain a snapshot of the
Italian scenario capturing the main directions of the research activities.
Furthermore, the distance of more than one year makes meaningful the bibliometric
analysis of the reviewed papers. The review shows a research community
distributed among different scientific disciplines, from chemistry, physics,
engineering, and material science, with a strong interest in collaborative works.
PMID- 28420111
TI - Plantago asiatica L. Ameliorates Puromycin Aminonucleoside-Induced Nephrotic
Syndrome by Suppressing Inflammation and Apoptosis.
AB - OBJECTIVE: Nephrotic syndrome, a kidney disease with a variety of causes, is
mainly characterized by heavy proteinuria, hypoproteinemia, and ascites. This
study was designed to evaluate the underlying mechanism of action of Plantago
asiatica L. (PAL) in treating nephrotic syndrome induced by puromycin
aminonucleoside. METHODS: PAL has been used in Asia as a traditional medicine and
dietary health supplement. Sprague-Dawley (SD) rats were intravenously injected
with puromycin aminonucleoside (75 mg/kg/day), then treated with either Losartan
(30 mg/kg/day) or PAL (200 mg/kg/day) by oral gavage for seven days. RESULTS: PAL
significantly decreased ascites, proteinuria level, and plasma lipid parameters.
In addition, treatment with PAL attenuated histological damage and
hypoalbuminemia. Treatment with PAL also restored podocin expression and reduced
inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte
chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and high
mobility group box-1 (HMGB1). Lower expression levels of the apoptosis markers
Bax, caspase-3 and capase-9 were documented in SD rats receiving PAL. PAL also
significantly decreased the phosphorylation levels of MAPKs such as ERK, JNK and
p38. CONCLUSION: As a multifunctional agent, PAL has a renoprotective effect in
nephrotic syndrome rat models. The anti-inflammatory and anti-apoptotic
properties, along with reductions in hyperlipidemia and ascites, represent
important therapeutic effects. These results indicate that Plantago asiatica is
likely to be a promising agent in the treatment of nephrotic syndrome.
PMID- 28420112
TI - The Association between Breakfast Skipping and Body Weight, Nutrient Intake, and
Metabolic Measures among Participants with Metabolic Syndrome.
AB - The effect of skipping breakfast on health, especially in adults, remains a
controversial topic. A secondary data analysis was conducted to examine
associations between breakfast eating patterns and weight loss, nutrient intake,
and metabolic parameters among participants with metabolic syndrome (MetS) (n =
240). Three randomly selected 24-h dietary recalls were collected from each
participant at baseline and at the one-year visit. Skipped breakfast was seen in
32.9% at baseline and in 17.4% at the one-year visit, respectively. At baseline,
after adjustment for demographics and physical activity, participants who ate
breakfast had a higher thiamin, niacin, and folate intake than did breakfast
skippers (p < 0.05); other selected parameters including body weight, dietary
quality scores, nutrient intake, and metabolic parameters showed no significant
differences between the two groups (p >= 0.05). From baseline to one year, after
adjustment for covariates, mean fat intake increased by 2.7% (95% confidence
intervals (CI): -1.0, 6.5%) of total energy in breakfast skippers in comparison
to the 1.2% decrease observed in breakfast eaters (95% CI: -3.4, 1.1%) (p =
0.02). Mean changes in other selected parameters showed no significant
differences between breakfast skippers and eaters (p > 0.05). This study did not
support the hypothesis that skipping breakfast has impact on body weight,
nutrient intakes, and selected metabolic measures in participants with MetS.
PMID- 28420113
TI - Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including
Insights into Essential Motifs of their Hydrodipyrrin Precursors.
AB - Synthetic bacteriochlorins-analogues of bacteriochlorophylls, Nature's near
infrared absorbers-are attractive for diverse photochemical studies. meso
Arylbacteriochlorins have been prepared by the self-condensation of a
dihydrodipyrrin-carbinol or dihydrodipyrrin-acetal following an Eastern-Western
(E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem
dimethyl group in each pyrroline ring to ensure stability toward oxidation. The
two routes differ in the location of the gem-dimethyl group at the respective 3-
or 2-position in the dihydrodipyrrin, and the method of synthesis of the
dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1
carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1
(aryl)carbinol, and upon subsequent acetylation, the corresponding
dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin-acetate). Self-condensation of
the dihydrodipyrrin-acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2
dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to
give a trans-A2B2-type meso-tetraarylbacteriochlorin (N-S route). In each case,
the aromatization process entails a 2e-/2H+ (aerobic) dehydrogenative oxidation
following the dihydrodipyrrin self-condensation. Comparison of a
tetrahydrodipyrrin-acetal (0%) versus a dihydrodipyrrin-acetal (41%) in
bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins
revealed the importance of resonance stabilization of the reactive hydrodipyrrin
intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins
have been prepared. The bacteriochlorins exhibit characteristic
bacteriochlorophyll-like absorption spectra, including a Qy band in the region
726-743 nm.
PMID- 28420114
TI - Fuzzy System-Based Target Selection for a NIR Camera-Based Gaze Tracker.
AB - Gaze-based interaction (GBI) techniques have been a popular subject of research
in the last few decades. Among other applications, GBI can be used by persons
with disabilities to perform everyday tasks, as a game interface, and can play a
pivotal role in the human computer interface (HCI) field. While gaze tracking
systems have shown high accuracy in GBI, detecting a user's gaze for target
selection is a challenging problem that needs to be considered while using a gaze
detection system. Past research has used the blinking of the eyes for this
purpose as well as dwell time-based methods, but these techniques are either
inconvenient for the user or requires a long time for target selection.
Therefore, in this paper, we propose a method for fuzzy system-based target
selection for near-infrared (NIR) camera-based gaze trackers. The results of
experiments performed in addition to tests of the usability and on-screen
keyboard use of the proposed method show that it is better than previous methods.
PMID- 28420116
TI - Construct Validity of an Obesity Risk Screening Tool in Two Age Groups.
AB - Home environment influences child health, but the impact varies as children move
into adolescence. The Family Nutrition and Physical Activity (FNPA) screening
tool has been used to evaluate home environments, but studies have not compared
the utility of the tool in different age groups. The purpose of this study was to
examine the efficacy of the FNPA tool in first and tenth grade samples. Parents
of first grade (n = 250) and tenth grade (n = 99) students completed the FNPA and
results were linked to body mass index (BMI) data. FNPA scores were examined by
gender, income, race, and school-level socioeconomic status (SES). Correlations
examined associations between FNPA scores and several BMI indicators. Logistic
and linear regression analyses evaluated the construct validity of the FNPA in
both groups. Mean FNPA score differed by age group, by SES in both age groups,
and by race in the first grade sample only. Correlations between FNPA score and
BMI indicators were higher in the first grade sample, but SES was significantly
associated with BMI only in tenth graders. The FNPA has stronger utility in
younger children, while school SES is a stronger predictor of adolescent weight
status.
PMID- 28420115
TI - A Cross-Sectional Study on Selected Correlates of High risk Sexual Behavior in
Polish Migrants Resident in the United Kingdom.
AB - Objective: To assess the correlates of the high risk sexual behaviors of Polish
migrants in the United Kingdom (UK) after 2004, and to compare such behaviors
before/after immigration. Methods: In 2013, a cross-sectional study was conducted
through the use of a Computer-assisted web interviewing surveying technique with
the use of a self-administered questionnaire. Results: Among 408 respondents
(56.9% women), with a median age of 32 years, significantly more admitted to
having unprotected sexual contact with a casual partner while in the UK (p <
0.0001) than while in Poland; more were engaged in sex after the use of
recreational drugs and alcohol (p < 0.0001 and p = 0.001 respectively). Being a
male was associated with greater odds of unprotected sex, sex after the use of
alcohol, and having multiple partners. Being single and having only been a
resident for a short time in the UK, presenting a lower self-esteem, were
predictors of unprotected sex. A total of 19.6% of the respondents admitted to
having been tested while in Poland, a lower (p < 0.0001) frequency than while in
the UK (49.5%); this referred to both genders; 1.2% (95% CI: 0.79-2.83%) reported
that they were HIV positive. Conclusions: Migration can create a vulnerability to
STIs, especially for single male migrants with low self-esteem, staying in the UK
for less than two years. The results point to strengthening strategies which help
reduce high risk sexual behavior among Polish migrants, and to introduce
interventions to promote an awareness of HIV sero-status.
PMID- 28420117
TI - Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with
Cisplatin on Ovarian Cancer Cells.
AB - Melittin, the main peptide present in bee venom, has been proposed as having
potential for anticancer therapy; the addition of melittin to cisplatin, a first
line treatment for ovarian cancer, may increase the therapeutic response in
cancer treatment via synergy, resulting in improved tolerability, reduced
relapse, and decreased drug resistance. Thus, this study was designed to compare
the metabolomic effects of melittin in combination with cisplatin in cisplatin
sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid
chromatography (LC) coupled with mass spectrometry (MS) was applied to identify
metabolic changes in A2780 (combination treatment 5 MUg/mL melittin + 2 MUg/mL
cisplatin) and A2780CR (combination treatment 2 MUg/mL melittin + 10 MUg/mL
cisplatin) cells. Principal components analysis (PCA) and orthogonal partial
least squares discriminant analysis (OPLS-DA) multivariate data analysis models
were produced using SIMCA-P software. All models displayed good separation
between experimental groups and high-quality goodness of fit (R2) and goodness of
prediction (Q2), respectively. The combination treatment induced significant
changes in both cell lines involving reduction in the levels of metabolites in
the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and
pyrimidine metabolism, and the arginine/proline pathway. The combination of
melittin with cisplatin that targets these pathways had a synergistic effect. The
melittin-cisplatin combination had a stronger effect on the A2780 cell line in
comparison with the A2780CR cell line. The metabolic effects of melittin and
cisplatin in combination were very different from those of each agent alone.
PMID- 28420118
TI - Ambient Air Pollution and Out-of-Hospital Cardiac Arrest in Beijing, China.
AB - Air pollutants are associated with cardiovascular death; however, there is
limited evidence of the effects of different pollutants on out-of-hospital
cardiac arrests (OHCAs) in Beijing, China. We aimed to investigate the
associations of OHCAs with the air pollutants PM2.5-10 (coarse particulate
matter), PM2.5 (particles <=2.5 MUm in aerodynamic diameter), nitrogen dioxide
(NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) between 2013
and 2015 using a time-stratified case-crossover study design. We obtained health
data from the nationwide emergency medical service database; 4720 OHCA cases of
cardiac origin were identified. After adjusting for relative humidity and
temperature, the highest odds ratios of OHCA for a 10 MUg/m3 increase in PM2.5
were observed at Lag Day 1 (1.07; 95% confidence interval (CI): 1.04-1.10), with
strong associations with advanced age (aged >=70 years) (1.09; 95% CI: 1.05-1.13)
and stroke history (1.11; 95% CI: 1.06-1.16). PM2.5-10 and NO2 also showed
significant associations with OHCAs, whereas SO2, CO, and O3 had no effects.
After simultaneously adjusting for NO2 and SO2 in a multi-pollutant model, PM2.5
remained significant. The effects of PM2.5 in the single-pollutant models for
cases with hypertension, respiratory disorders, diabetes mellitus, and heart
disease were higher than those for cases without these complications; however,
the differences were not statistically significant. The results support that
elevated PM2.5 exposure contributes to triggering OHCA, especially in those who
are advanced in age and have a history of stroke.
PMID- 28420119
TI - The Modeling and Simulation of the Galvanic Coupling Intra-Body Communication via
Handshake Channel.
AB - Intra-body communication (IBC) is a technology using the conductive properties of
the body to transmit signal, and information interaction by handshake is regarded
as one of the important applications of IBC. In this paper, a method for modeling
the galvanic coupling intra-body communication via handshake channel is proposed,
while the corresponding parameters are discussed. Meanwhile, the mathematical
model of this kind of IBC is developed. Finally, the validity of the developed
model has been verified by measurements. Moreover, its characteristics are
discussed and compared with that of the IBC via single body channel. Our results
indicate that the proposed method will lay a foundation for the theoretical
analysis and application of the IBC via handshake channel.
PMID- 28420121
TI - A 7.4 ps FPGA-Based TDC with a 1024-Unit Measurement Matrix.
AB - In this paper, a high-resolution time-to-digital converter (TDC) based on a field
programmable gate array (FPGA) device is proposed and tested. During the
implementation, a new architecture of TDC is proposed which consists of a
measurement matrix with 1024 units. The utilization of routing resources as the
delay elements distinguishes the proposed design from other existing designs,
which contributes most to the device insensitivity to variations of temperature
and voltage. Experimental results suggest that the measurement resolution is 7.4
ps, and the INL (integral nonlinearity) and DNL (differential nonlinearity) are
11.6 ps and 5.5 ps, which indicates that the proposed TDC offers high performance
among the available TDCs. Benefitting from the FPGA platform, the proposed TDC
has superiorities in easy implementation, low cost, and short development time.
PMID- 28420120
TI - Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to
Treatment Type and Line: A Retrospective Multinational Study.
AB - Acute erythroleukemia (AEL) is a rare disease typically associated with a poor
prognosis. The median survival ranges between 3-9 months from initial diagnosis.
Hypomethylating agents (HMAs) have been shown to prolong survival in patients
with myelodysplastic syndromes (MDS) and AML, but there is limited data of their
efficacy in AEL. We collected data from 210 AEL patients treated at 28
international sites. Overall survival (OS) and PFS were estimated using the
Kaplan-Meier method and the log-rank test was used for subgroup comparisons.
Survival between treatment groups was compared using the Cox proportional hazards
regression model. Eighty-eight patients were treated with HMAs, 44 front line,
and 122 with intensive chemotherapy (ICT). ICT led to a higher overall response
rate (complete or partial) compared to first-line HMA (72% vs. 46.2%,
respectively; p <= 0.001), but similar progression-free survival (8.0 vs. 9.4
months; p = 0.342). Overall survival was similar for ICT vs. HMAs (10.5 vs. 13.7
months; p = 0.564), but patients with high-risk cytogenetics treated with HMA
first-line lived longer (7.5 for ICT vs. 13.3 months; p = 0.039). Our results
support the therapeutic value of HMA in AEL.
PMID- 28420122
TI - The Effect of Salt Intake and Potassium Supplementation on Serum Gastrin Levels
in Chinese Adults: A Randomized Trial.
AB - Excess dietary salt is strongly correlated with cardiovascular disease,
morbidity, and mortality. Conversely, potassium likely elicits favorable effects
against cardiovascular disorders. Gastrin, which is produced by the G-cells of
the stomach and duodenum, can increase renal sodium excretion and regulate blood
pressure by acting on the cholecystokinin B receptor. The aim of our study was to
assess the effects of altered salt and potassium supplementation on serum gastrin
levels in humans. A total of 44 subjects (38-65 years old) were selected from a
rural community in northern China. All subjects were sequentially maintained on a
relatively low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for 7
days (18.0 g/day of NaCl), and then a high-salt diet supplemented with potassium
for another 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). The high-salt intake
significantly increased serum gastrin levels (15.3 +/- 0.3 vs. 17.6 +/- 0.3
pmol/L). This phenomenon was alleviated through potassium supplementation (17.6
+/- 0.3 vs. 16.5 +/- 0.4 pmol/L). Further analyses revealed that serum gastrin
was positively correlated with 24 h urinary sodium excretion (r = 0.476, p <
0.001). By contrast, gastrin level was negatively correlated with blood pressure
in all dietary interventions (r = -0.188, p = 0.031). The present study indicated
that variations in dietary salt and potassium supplementation affected the serum
gastrin concentrations in the Chinese subjects.
PMID- 28420123
TI - Stability of Bioactive Compounds in Broccoli as Affected by Cutting Styles and
Storage Time.
AB - Broccoli contains bioactive molecules and thus its consumption is related with
the prevention of chronic and degenerative diseases. The application of wounding
stress to horticultural crops is a common practice, since it is the basis for the
fresh-cut produce industry. In this study, the effect of four different cutting
styles (CSs) (florets (CS1), florets cut into two even pieces (CS2), florets cut
into four even pieces (CS3), and florets processed into chops (CS4)) and storage
time (0 and 24 h at 20 degrees C) on the content of bioactive compounds in
broccoli was evaluated. Immediately after cutting, 5-O-caffeoylquinic acid and
caffeic acid content increased by 122.4% and 41.6% in CS4 and CS2, respectively.
Likewise, after storage, 3-O-caffeoylquinic acid and 5-O-caffeoylquinic acid
increased by 46.7% and 98.2%, respectively in CS1. Glucoerucin and
gluconasturtiin content decreased by 62% and 50%, respectively in CS3; whereas
after storage most glucosinolates increased in CS1. Total isothiocyanates,
increased by 133% immediately in CS4, and after storage CS1 showed 65% higher
levels of sulforaphane. Total ascorbic acid increased 35% after cutting in CS2,
and remained stable after storage. Results presented herein would allow broccoli
producers to select proper cutting styles that preserve or increase the content
of bioactive molecules.
PMID- 28420124
TI - Applying Broadband Dielectric Spectroscopy (BDS) for the Biophysical
Characterization of Mammalian Tissues under a Variety of Cellular Stresses.
AB - The dielectric properties of biological tissues can contribute non-invasively to
a better characterization and understanding of the structural properties and
physiology of living organisms. The question we asked, is whether these induced
changes are effected by an endogenous or exogenous cellular stress, and can they
be detected non-invasively in the form of a dielectric response, e.g., an AC
conductivity switch in the broadband frequency spectrum. This study constitutes
the first methodological approach for the detection of environmental stress
induced damage in mammalian tissues by the means of broadband dielectric
spectroscopy (BDS) at the frequencies of 1-106 Hz. Firstly, we used non-ionizing
(NIR) and ionizing radiation (IR) as a typical environmental stress.
Specifically, rats were exposed to either digital enhanced cordless
telecommunication (DECT) radio frequency electromagnetic radiation or to gamma
radiation, respectively. The other type of stress, characterized usually by high
genomic instability, was the pathophysiological state of human cancer (lung and
prostate). Analyzing the results of isothermal dielectric measurements provided
information on the tissues' water fraction. In most cases, our methodology proved
sufficient in detecting structural changes, especially in the case of IR and
malignancy. Useful specific dielectric response patterns are detected and
correlated with each type of stress. Our results point towards the development of
a dielectric-based methodology for better understanding and, in a relatively
invasive way, the biological and structural changes effected by radiation and
developing lung or prostate cancer often associated with genomic instability.
PMID- 28420125
TI - Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological
Activity.
AB - Citrus plants contain large amounts of flavonoids with beneficial effects on
human health. In the present study, the antioxidant and anti-inflammatory
potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro
and ex vivo, using the murine macrophages cell line J774A.1 and primary
peritoneal macrophages. Following simulated gastro-intestinal digestion, the in
vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using
the human cell line Caco-2 grown as monolayers on a transwell membrane. Data
demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant
and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was
compared to the bioavailable one (CsB). Results revealed that Citrus extract were
able to reduce macrophages pro-inflammatory mediators, including nitric oxide,
iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis
polyphenols was associated with antioxidant effects, such as a reduction of
reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression.
Our results provide evidence that the bioavailable polyphenolic constituents of
the Citrussinensis extract accumulate prevalently at intestinal level and could
reach systemic circulation exerting their effect. The bioavailable fraction
showed a higher anti-inflammatory and antioxidant potential compared to the
initial extract, thus highlighting its potential nutraceutical value.
PMID- 28420126
TI - Novel Genetic Variants Associated with Child Refractory Esophageal Stricture with
Food Allergy by Exome Sequencing.
AB - BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food
allergy. Its etiology and pathogenesis are not fully understood. Identification
of novel genetic variants associated with this disease by exome sequencing (exome
seq) may provide new mechanistic insights and new therapeutic targets. METHODS:
To identify new and novel disease-associating variants, whole-exome sequencing
was performed on an Illumina NGS platform in three children with RES as well as
food allergy. RESULTS: A total of 91,024 variants were identified. By filtering
out 'normal variants' against those of the 1000 Genomes Project, we identified
12,741 remaining variants which are potentially associated with RES plus food
allergy. Among these variants, there are 11,539 single nucleotide polymorphisms
(SNPs), 627 deletions, 551 insertions and 24 mixture variants. These variants are
located in 1370 genes. They are enriched in biological processes or pathways such
as cell adhesion, digestion, receptor metabolic process, bile acid transport and
the neurological system. By the PubMatrix analysis, 50 out of the top 100 genes,
which contain most variants, have not been previously associated with any of the
17 allergy-associated diseases. These 50 genes represent newly identified allergy
associated genes. Those variants of 627 deletions and 551 insertions have also
not been reported before in RES with food allergy. CONCLUSIONS: Exome-seq is
potentially a powerful tool to identify potential new biomarkers for RES with
food allergy. This study has identified a number of novel genetic variants,
opening new avenues of research in RES plus food allergy. Additional validation
in larger and different patient populations and further exploration of the
underlying molecular mechanisms are warranted.
PMID- 28420127
TI - Glycosaminoglycan Binding and Non-Endocytic Membrane Translocation of Cell
Permeable Octaarginine Monitored by Real-Time In-Cell NMR Spectroscopy.
AB - Glycosaminoglycans (GAGs), which are covalently-linked membrane proteins at the
cell surface have recently been suggested to involve in not only endocytic
cellular uptake but also non-endocytic direct cell membrane translocation of
arginine-rich cell-penetrating peptides (CPPs). However, in-situ comprehensive
observation and the quantitative analysis of the direct membrane translocation
processes are challenging, and the mechanism therefore remains still unresolved.
In this work, real-time in-cell NMR spectroscopy was applied to investigate the
direct membrane translocation of octaarginine (R8) into living cells. By
introducing 4-trifluoromethyl-l-phenylalanine to the N terminus of R8, the non
endocytic membrane translocation of 19F-labeled R8 (19F-R8) into a human myeloid
leukemia cell line was observed at 4 degrees C with a time resolution in the
order of minutes. 19F NMR successfully detected real-time R8 translocation: the
binding to anionic GAGs at the cell surface, followed by the penetration into the
cell membrane, and the entry into cytosol across the membrane. The NMR
concentration analysis enabled quantification of how much of R8 was staying in
the respective translocation processes with time in situ. Taken together, our in
cell NMR results provide the physicochemical rationale for spontaneous
penetration of CPPs in cell membranes.
PMID- 28420128
TI - AR Signaling and the PI3K Pathway in Prostate Cancer.
AB - Prostate cancer is a leading cause of cancer-related death in men worldwide.
Aberrant signaling in the androgen pathway is critical in the development and
progression of prostate cancer. Despite ongoing reliance on androgen receptor
(AR) signaling in castrate resistant disease, in addition to the development of
potent androgen targeting drugs, patients invariably develop treatment
resistance. Interactions between the AR and PI3K pathways may be a mechanism of
treatment resistance and inhibitors of this pathway have been developed with
variable success. Herein we outline the role of the PI3K pathway in prostate
cancer and, in particular, its association with androgen receptor signaling in
the pathogenesis and evolution of prostate cancer, as well as a review of the
clinical utility of PI3K targeting.
PMID- 28420129
TI - Hand Motion Detection in fNIRS Neuroimaging Data.
AB - As the number of people diagnosed with movement disorders is increasing, it
becomes vital to design techniques that allow the better understanding of human
brain in naturalistic settings. There are many brain imaging methods such as
fMRI, SPECT, and MEG that provide the functional information of the brain.
However, these techniques have some limitations including immobility, cost, and
motion artifacts. One of the most emerging portable brain scanners available
today is functional near-infrared spectroscopy (fNIRS). In this study, we have
conducted fNIRS neuroimaging of seven healthy subjects while they were performing
wrist tasks such as flipping their hand with the periods of rest (no movement).
Different models of support vector machine is applied to these fNIRS neuroimaging
data and the results show that we could classify the action and rest periods with
the accuracy of over 80% for the fNIRS data of individual participants. Our
results are promising and suggest that the presented classification method for
fNIRS could further be applied to real-time applications such as brain computer
interfacing (BCI), and into the future steps of this research to record brain
activity from fNIRS and EEG, and fuse them with the body motion sensors to
correlate the activities.
PMID- 28420130
TI - Gaseous Elemental Mercury and Total and Leached Mercury in Building Materials
from the Former Hg-Mining Area of Abbadia San Salvatore (Central Italy).
AB - Mercury has a strong environmental impact since both its organic and inorganic
forms are toxic, and it represents a pollutant of global concern. Liquid Hg is
highly volatile and can be released during natural and anthropogenic processes in
the hydrosphere, biosphere and atmosphere. In this study, the distribution of
Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations
on paint, plaster, roof tiles, concrete, metals, dust and wood structures were
determined in the main buildings and structures of the former Hg-mining area of
Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into
seven units) covers a surface of about 65 ha and contains mining structures and
managers' and workers' buildings. Nine surveys of GEM measurements were carried
out from July 2011 to August 2015 for the buildings and structures located in
Units 2, 3 and 6, the latter being the area where liquid mercury was produced.
Measurements were also performed in February, April, July, September and December
2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a
strong variability in time and space mostly depending on ambient temperature and
the operational activities that were carried out in each building. The Unit 2
surveys carried out in the hotter period (from June to September) showed GEM
concentrations up to 27,500 ng.m-3, while in Unit 6, they were on average much
higher, and occasionally, they saturated the GEM measurement device (>50,000 ng.m
3). Concentrations of total (in mg.kg-1) and leached (in MUg.L-1) mercury
measured in different building materials (up to 46,580 mg.kg-1 and 4470 mg.L-1,
respectively) were highly variable, being related to the edifice or mining
structure from which they were collected. The results obtained in this study are
of relevant interest for operational cleanings to be carried out during
reclamation activities.
PMID- 28420132
TI - A Smart Voltage and Current Monitoring System for Three Phase Inverters Using an
Android Smartphone Application.
AB - In this paper, a new smart voltage and current monitoring system (SVCMS)
technique is proposed. It monitors a three phase electrical system using an
Arduino platform as a microcontroller to read the voltage and current from
sensors and then wirelessly send the measured data to monitor the results using a
new Android application. The integrated SVCMS design uses an Arduino Nano V3.0 as
the microcontroller to measure the results from three voltage and three current
sensors and then send this data, after calculation, to the Android smartphone
device of an end user using Bluetooth HC-05. The Arduino Nano V3.0 controller and
Bluetooth HC-05 are a cheap microcontroller and wireless device, respectively.
The new Android smartphone application that monitors the voltage and current
measurements uses the open source MIT App Inventor 2 software. It allows for
monitoring some elementary fundamental voltage power quality properties. An
effort has been made to investigate what is possible using available off-the
shelf components and open source software.
PMID- 28420131
TI - Work Characteristics Associated with Physical Functioning in Women.
AB - Women make up almost half of the labor force with older women becoming a growing
segment of the population. Work characteristics influence physical functioning
and women are at particular risk for physical limitations. However, little
research has explored the effects of work characteristics on women's physical
functioning. U.S. women between the ages of 50 and 79 were enrolled in the
Women's Health Initiative Observational Study between 1993 and 1998. Women
provided job titles and years worked at their three longest-held jobs (n =
79,147). Jobs were linked to characteristics in the Occupational Information
Network. Three categories of job characteristics related to substantive
complexity, physical demand, and social collaboration emerged. The association
between job characteristics and physical limitations in later life, measured
using a SF-36 Physical Functioning score <25th percentile, was examined using
modified Poisson regression. After controlling for confounding variables, high
physical demand was positively associated with physical limitations (RR = 1.09
CI: 1.06-1.12) and substantively complex work was negatively associated (RR =
0.94, CI: 0.91-0.96). Jobs requiring complex problem solving, active learning,
and critical thinking were associated with better physical functioning. Employers
should explore opportunities to reduce strain from physically demanding jobs and
incorporate substantively complex tasks into women's work to improve long-term
health.
PMID- 28420133
TI - Using Dimensionality Reduction Techniques for Refining Passive Indoor Positioning
Systems Based on Radio Fingerprinting.
AB - Indoor positioning methods based on fingerprinting and radio signals rely on the
quality of the radio map. For example, for room-level classification purposes, it
is required that the signal observations related to each room exhibit significant
differences in their RSSI values. However, it is difficult to verify and
visualize that separability since radio maps are constituted by multi-dimensional
observations whose dimension is directly related to the number of access points
or monitors being employed for localization purposes. In this paper, we propose a
refinement cycle for passive indoor positioning systems, which is based on
dimensionality reduction techniques, to evaluate the quality of a radio map. By
means of these techniques and our own data representation, we have defined two
different visualization methods to obtain graphical information about the quality
of a particular radio map in terms of overlapping areas and outliers. That
information will be useful to determine whether new monitors are required or some
existing ones should be moved. We have performed an exhaustive experimental
analysis based on a variety of different scenarios, some deployed by our own
research group and others corresponding to a well-known existing dataset widely
analyzed by the community, in order to validate our proposal. As we will show,
among the different combinations of data representation methods and
dimensionality reduction techniques that we discuss, we have found that there are
some specific configurations that are more useful in order to perform the
refinement process.
PMID- 28420134
TI - Visual Detection and Tracking System for a Spherical Amphibious Robot.
AB - With the goal of supporting close-range observation tasks of a spherical
amphibious robot, such as ecological observations and intelligent surveillance, a
moving target detection and tracking system was designed and implemented in this
study. Given the restrictions presented by the amphibious environment and the
small-sized spherical amphibious robot, an industrial camera and vision
algorithms using adaptive appearance models were adopted to construct the
proposed system. To handle the problem of light scattering and absorption in the
underwater environment, the multi-scale retinex with color restoration algorithm
was used for image enhancement. Given the environmental disturbances in practical
amphibious scenarios, the Gaussian mixture model was used to detect moving
targets entering the field of view of the robot. A fast compressive tracker with
a Kalman prediction mechanism was used to track the specified target. Considering
the limited load space and the unique mechanical structure of the robot, the
proposed vision system was fabricated with a low power system-on-chip using an
asymmetric and heterogeneous computing architecture. Experimental results
confirmed the validity and high efficiency of the proposed system. The design
presented in this paper is able to meet future demands of spherical amphibious
robots in biological monitoring and multi-robot cooperation.
PMID- 28420135
TI - A Prosthetic Hand Body Area Controller Based on Efficient Pattern Recognition
Control Strategies.
AB - Poliarticulated prosthetic hands represent a powerful tool to restore
functionality and improve quality of life for upper limb amputees. Such devices
offer, on the same wearable node, sensing and actuation capabilities, which are
not equally supported by natural interaction and control strategies. The control
in state-of-the-art solutions is still performed mainly through complex encoding
of gestures in bursts of contractions of the residual forearm muscles, resulting
in a non-intuitive Human-Machine Interface (HMI). Recent research efforts explore
the use of myoelectric gesture recognition for innovative interaction solutions,
however there persists a considerable gap between research evaluation and
implementation into successful complete systems. In this paper, we present the
design of a wearable prosthetic hand controller, based on intuitive gesture
recognition and a custom control strategy. The wearable node directly actuates a
poliarticulated hand and wirelessly interacts with a personal gateway (i.e., a
smartphone) for the training and personalization of the recognition algorithm.
Through the whole system development, we address the challenge of integrating an
efficient embedded gesture classifier with a control strategy tailored for an
intuitive interaction between the user and the prosthesis. We demonstrate that
this combined approach outperforms systems based on mere pattern recognition,
since they target the accuracy of a classification algorithm rather than the
control of a gesture. The system was fully implemented, tested on healthy and
amputee subjects and compared against benchmark repositories. The proposed
approach achieves an error rate of 1.6% in the end-to-end real time control of
commonly used hand gestures, while complying with the power and performance
budget of a low-cost microcontroller.
PMID- 28420136
TI - Discovery of an Octahedral Silicon Complex as a Potent Antifungal Agent.
AB - Octahedral transition metal complexes have been shown to have tremendous
applications in chemical biology and medicinal chemistry. Meanwhile, structural
transition metals can be replaced by inert octahedral silicon in a proof-of
principle study. We here introduce the first example of octahedral silicon
complexes, which can very well serve as an efficient antimicrobial agent. The
typical silicon arenediolate complex 1 {[(phen)2Si(OO)](PF6)2, with phen = 1,10
phenanthroline, OO = 9,10-phenanthrenediolate} exhibited significant inhibition
towards the growth of Cryptococcus neoformans with MIC and MFC values of 4.5 and
11.3 MUM, respectively. Moreover, it was fungicidal against both proliferative
and quiescent Cryptococcus cells. This work may set the stage for the development
of novel antifungal drugs based upon hexacoodinate silicon scaffolds.
PMID- 28420137
TI - Modification of the Mycotoxin Deoxynivalenol Using Microorganisms Isolated from
Environmental Samples.
AB - The trichothecene mycotoxin deoxynivalenol (DON) is a common contaminant of
wheat, barley, and maize. New strategies are needed to reduce or eliminate DON in
feed and food products. Microorganisms from plant and soil samples collected in
Blacksburg, VA, USA, were screened by incubation in a mineral salt media
containing 100 MUg/mL DON and analysis by gas chromatography mass spectrometry
(GC/MS). Two mixed cultures derived from soil samples consistently decreased DON
levels in assays using DON as the sole carbon source. Nuclear magnetic resonance
(NMR) analysis indicated that 3-keto-4-deoxynivalenol was the major by-product of
DON. Via 16S rRNA sequencing, these mixed cultures, including mostly members of
the genera Acinetobacter, Leadbetterella, and Gemmata, were revealed. Incubation
of one of these mixed cultures with wheat samples naturally contaminated with 7.1
MUg/mL DON indicated nearly complete conversion of DON to the less toxic 3-epimer
DON (3-epi-DON). Our work extends previous studies that have demonstrated the
potential for bioprospecting for microorganisms from the environment to remediate
or modify mycotoxins for commercial applications, such as the reduction of
mycotoxins in fuel ethanol co-products.
PMID- 28420138
TI - Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis
Induced Cardiac Dysfunction.
AB - Cardiac dysfunction, in particular of the left ventricle, is a common and early
event in sepsis, and is strongly associated with an increase in patients'
mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and
transient generation of the lipid mediator ceramide-is involved in both the
regulation of host response in sepsis as well as in the pathogenesis of chronic
heart failure. This study determined the degree and the potential role to which
SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both
genetically deficient and pharmacologically-treated animals in a polymicrobial
sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac
function, markers of oxidative stress as well as troponin I levels were found to
be improved in desipramine-treated animals, desipramine being an inhibitor of
ceramide formation. Additionally, ceramide formation in cardiac tissue was
dysregulated in SMPD1+/+ as well as SMPD1-/- animals, whereas desipramine
pretreatment resulted in stable, but increased ceramide content during host
response. This was a result of elevated de novo synthesis. Strikingly,
desipramine treatment led to significantly improved levels of surrogate markers.
Furthermore, similar results in desipramine-pretreated SMPD1-/- littermates
suggest an SMPD1-independent pathway. Finally, a pattern of differentially
expressed transcripts important for regulation of apoptosis as well as
antioxidative and cytokine response supports the concept that desipramine
modulates ceramide formation, resulting in beneficial myocardial effects. We
describe a novel, protective role of desipramine during sepsis-induced cardiac
dysfunction that controls ceramide content. In addition, it may be possible to
modulate cardiac function during host response by pre-conditioning with the Food
and Drug Administration (FDA)-approved drug desipramine.
PMID- 28420139
TI - Interplay between Oxidative Stress and Nutrient Sensing Signaling in the
Developmental Origins of Cardiovascular Disease.
AB - Cardiovascular disease (CVD) presents a global health burden, despite recent
advances in management. CVD can originate from early life by so-called
"developmental origins of health and disease" (DOHaD). Epidemiological and
experimental evidence supports that early-life insults can induce programming of
later CVD. Underlying the DOHaD concept, early intervention may offset
programming process to prevent the development of CVD, namely reprogramming.
Oxidative stress and nutrient sensing signals have been considered to be major
mechanisms of cardiovascular programming, while the interplay between these two
mechanisms have not been examined in detail. This review summarizes current
evidence that supports the link between oxidative stress and nutrient sensing
signaling to cardiovascular programming, with an emphasis on the l-arginine
asymmetric dimethylarginine (ADMA)-nitric oxide (NO) pathway. This review
provides an overview of evidence from human studies supporting fetal programming
of CVD, insight from animal models of cardiovascular programming and oxidative
stress, impact of the l-arginine-ADMA-NO pathway in cardiovascular programming,
the crosstalk between l-arginine metabolism and nutrient sensing signals, and
application of reprogramming interventions to prevent the programming of CVD. A
greater understanding of the mechanisms underlying cardiovascular programming is
essential to developing early reprogramming interventions to combat the globally
growing epidemic of CVD.
PMID- 28420140
TI - Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and
Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis
Patients.
AB - Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its
antioxidant and anti-inflammatory activities have been demonstrated in in vitro
and in vivo animal models. The aim of this study was to investigate the activity
of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies
obtained during colonoscopy from 14 patients with active UC were immediately
placed in an organ culture chamber and challenged with lipopolysaccharide from
Escherichia coli (EC-LPS) at 1 MUg/mL in the presence or absence of 3 mM OLE. The
expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in
total protein extracts from treated colonic biopsies by Western blotting. Levels
of IL-17 were also measured in culture supernatant by ELISA. A microscopic
evaluation of the cultured biopsies was performed by conventional histology and
immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower
in samples treated with OLE + EC-LPS compared with those treated with EC-LPS
alone (0.80 +/- 0.15 arbitrary units (a.u.) vs. 1.06 +/- 0.19 a.u., p = 0.003,
and 0.71 +/- 0.08 a.u. vs. 1.26 +/- 0.42 a.u., p = 0.03, respectively) as were
the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic
samples (21.16 +/- 8.64 pg/mL vs. 40.67 +/- 9.24 pg/mL, p = 0.01).
Histologically, OLE-treated colonic samples showed an amelioration of
inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while
CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in
colonic biopsies from UC patients. These new data support a potential role of OLE
in the treatment of UC.
PMID- 28420142
TI - Cross-Spectral Local Descriptors via Quadruplet Network.
AB - This paper presents a novel CNN-based architecture, referred to as Q-Net, to
learn local feature descriptors that are useful for matching image patches from
two different spectral bands. Given correctly matched and non-matching cross
spectral image pairs, a quadruplet network is trained to map input image patches
to a common Euclidean space, regardless of the input spectral band. Our approach
is inspired by the recent success of triplet networks in the visible spectrum,
but adapted for cross-spectral scenarios, where, for each matching pair, there
are always two possible non-matching patches: one for each spectrum. Experimental
evaluations on a public cross-spectral VIS-NIR dataset shows that the proposed
approach improves the state-of-the-art. Moreover, the proposed technique can also
be used in mono-spectral settings, obtaining a similar performance to triplet
network descriptors, but requiring less training data.
PMID- 28420141
TI - Coordinated Actions of MicroRNAs with other Epigenetic Factors Regulate Skeletal
Muscle Development and Adaptation.
AB - Epigenetics plays a pivotal role in regulating gene expression in development, in
response to cellular stress or in disease states, in virtually all cell types.
MicroRNAs (miRNAs) are short, non-coding RNA molecules that mediate RNA silencing
and regulate gene expression. miRNAs were discovered in 1993 and have been
extensively studied ever since. They can be expressed in a tissue-specific manner
and play a crucial role in tissue development and many biological processes.
miRNAs are responsible for changes in the cell epigenome because of their ability
to modulate gene expression post-transcriptionally. Recently, numerous studies
have shown that miRNAs and other epigenetic factors can regulate each other or
cooperate in regulating several biological processes. On the one hand, the
expression of some miRNAs is silenced by DNA methylation, and histone
modifications have been demonstrated to modulate miRNA expression in many cell
types or disease states. On the other hand, miRNAs can directly target epigenetic
factors, such as DNA methyltransferases or histone deacetylases, thus regulating
chromatin structure. Moreover, several studies have reported coordinated actions
between miRNAs and other epigenetic mechanisms to reinforce the regulation of
gene expression. This paper reviews multiple interactions between miRNAs and
epigenetic factors in skeletal muscle development and in response to stimuli or
disease.
PMID- 28420143
TI - Biotinylated Chlorin and Its Zinc and Indium Complexes: Synthesis and In Vitro
Biological Evaluation for Photodynamic Therapy.
AB - The synthesis and characterization of biotinylated chlorin photosensitizer and
the corresponding zinc and indium complexes are described for potential
applications in photodynamic therapy (PDT) for cancer. Phototoxicity of the
biotin-chlorin conjugate and the metallated complexes was determined in colon
carcinoma CT26 cell lines known to overexpress biotin (Vit B7) receptors. Cell
survival assay indicated that the biotinylated chlorin and indium complex showed
increased cell growth inhibition than the zinc complex and the starting chlorin
(methyl pheophorbide). Fluorescence microcopy studies revealed the generation of
apoptotic cells upon light irradiation of colon cells treated with the indium
complex. Targeting biotin receptors in cancer cells can improve specificity of
photosensitizers for PDT applications.
PMID- 28420144
TI - Retinoids Regulate Adipogenesis Involving the TGFbeta/SMAD and Wnt/beta-Catenin
Pathways in Human Bone Marrow Mesenchymal Stem Cells.
AB - Retinoids may regulate cell differentiation as ligands of retinoic acid receptors
(RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted
adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein
beta (C/EBPbeta) in the early stages, but blocked adipogenesis at a later stage
in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted
adipogenesis at all time points in hBMSCs. The effect of RAR agonists was
mediated mainly by the RARbeta subtype. RAR agonists, in contrast to RXR
agonists, significantly promoted the expression of RARbeta. Knockdown of the
RARbeta gene via small hairpin RNA (shRNA) attenuated the inhibition of RAR
agonists toward adipogenesis. Furthermore, we found that RAR agonists upregulated
the transforming growth factor beta (TGFbeta)/SMAD pathway and Wnt/beta-catenin
pathway on adipogenesis in hBMSCs, and the stimulating effects were noticeably
decreased with the RARbeta gene knockdown. Both RAR agonists and RXR agonists
inhibited adipogenesis and blocked the promoter activity of C/EBPbeta and
peroxisome proliferator-activated receptor gamma (PPARgamma) in SW872 cell. These
results indicated the RAR agonists perform dual roles in adipogenesis in hBMSCs,
and the TGFbeta/SMAD pathway and Wnt/beta-catenin pathway may involve the
inhibitory effect of RAR agonists. RARbeta is the main receptor subtype mediating
the effect. The roles of RXR agonists in adipogenesis exhibited cell type
specific differences, and may be based on the integration of signals from
different RXR dimers.
PMID- 28420145
TI - Evaluation of Polyphenolic Content, Antioxidant and Diuretic Activities of Six
Fumaria Species.
AB - Romanian traditional medicine describes the use of aerial parts of Fumaria
species to treat hepatobiliary diseases as well as diuretic agents. The present
study aims to investigate the chemical composition, antioxidant properties, and
diuretic effects of several Fumaria species. LC/MS analysis revealed that Fumaria
species contain phenolic acids and high amounts of flavonoids with rutin and
isoquercitrin as main compounds. Concerning antioxidant capacity, the most
significant results were obtained for F. capreolata and F. vailantii. Both
species showed a good correlation between the antioxidant capacity and a high
amount of flavonoids. Furthermore, the extracts of F. officinalis and F.
schleicheri produced a strong increase in urinary volumetric excretion of saline
loaded rats, 24 h after the oral administration of a single dose of 250 mg/kg bw.
Moreover, both extracts of F. officinalis and F. schleicheri increased the
urinary excretion of Na+ and K+. Results from the present study offer a new
perspective concerning the chemical composition and bioactivities of
traditionally used fumitory species.
PMID- 28420146
TI - Optimization of Ultrasound-Assisted Extraction of Antioxidants from the Mung Bean
Coat.
AB - Mung bean (Vigna radiata) sprout is commonly consumed as a vegetable, while the
coat of the germinated mung bean is a waste. In this paper, an ultrasound
assisted extraction method has been developed to extract natural antioxidants
from the seed coat of mung bean. Several experimental parameters-which included
ethanol concentration, solvent/material ratio, ultrasound extraction time,
temperature, and power-were studied in single-factor experiments. The interaction
of three key experimental parameters (ethanol concentration, solvent/material
ratio, and ultrasonic extraction time) was further investigated by response
surface method. Besides, traditional extracting methods, including maceration and
Soxhlet extraction methods, were also carried out for comparison. The results
suggested that the best extracting condition was 37.6% (v/v) of ethanol
concentration, 35.1:1 mL/g of solvent/material ratio and ultrasonic extraction of
46.1 min at 70 degrees C under 500 W ultrasonic irradiation. The antioxidant
capacity (178.28 +/- 7.39 umol Trolox/g DW) was much stronger than those obtained
by the maceration extraction process (158.66 +/- 4.73 umol Trolox/g DW) and the
Soxhlet extraction process (138.42 +/- 3.63 umol Trolox/g DW). In addition,
several antioxidant components in the extract were identified and quantified.
This study is helpful for value-added utilization of the waste from germinated
mung bean.
PMID- 28420147
TI - Intake Levels of Fish in the UK Paediatric Population.
AB - The United Kingdom (UK) is an island and its culture, including diet, is heavily
influenced by the maritime resources. Dietary guidance in the UK recommends
intake of fish, which provides important nutrients, such as long-chain omega-3
polyunsaturated fatty acids (n-3 PUFA). This study was designed to describe the
fish intake habits of UK children using a nationally representative sample.
Dietary and socio-demographic data of children 2-18 (N = 2096) in the National
Diet and Nutrition Survey Rolling Program (NDNS) Years 1-4 (2008-2012) were
extracted. Average nutrient and food intakes were estimated. Logistic regression
models were used to predict the meeting of fish intake recommendations,
controlling for age, sex, income, total energy intake, and survey year. All
analyses were conducted using survey routines and dietary survey weights. In this
nationally representative study, 4.7% of children met the fish and 4.5% the oily
fish intake recommendations; only 1.3% of the population met both
recommendations. Fish intake levels did not significantly change with children's
increasing age. Higher vegetable but lower meat consumption predicted meeting the
fish intake recommendations, indicating that children eating fish have better
diet quality than non-consumers. Further research is needed to explore how intake
behaviours can be changed to improve children's diet quality.
PMID- 28420149
TI - Advanced Stage at Presentation Remains a Major Factor Contributing to Breast
Cancer Survival Disparity between Public and Private Hospitals in a Middle-Income
Country.
AB - Background: Survival disparities in cancer are known to occur between public and
private hospitals. We compared breast cancer presentation, treatment and survival
between a public academic hospital and a private hospital in a middle-income
country. Methods: The demographics, clinical characteristics, treatment and
overall survival (OS) of 2767 patients with invasive breast carcinoma diagnosed
between 2001 and 2011 in the public hospital were compared with 1199 patients
from the private hospital. Results: Compared to patients in the private hospital,
patients from the public hospital were older at presentation, and had more
advanced cancer stages. They were also more likely to receive mastectomy and
chemotherapy but less radiotherapy. The five-year OS in public patients was
significantly lower than in private patients (71.6% vs. 86.8%). This difference
was largely attributed to discrepancies in stage at diagnosis and, although to a
much smaller extent, to demographic differences and treatment disparities. Even
following adjustment for these factors, patients in the public hospital remained
at increased risk of mortality compared to their counterparts in the private
hospital (Hazard Ratio: 1.59; 95% Confidence Interval: 1.36-1.85). Conclusion:
Late stage at diagnosis appears to be a major contributing factor explaining the
breast cancer survival disparity between public and private patients in this
middle-income setting.
PMID- 28420148
TI - Differential Effect of Sucrose and Fructose in Combination with a High Fat Diet
on Intestinal Microbiota and Kidney Oxidative Stress.
AB - There is controversial information about the adverse effect of sucrose (S) or
fructose (F) in the development of obesity. Thus, the purpose of the study was to
evaluate the effect of S or F in a high fat diet (HF) on gut microbiota and renal
oxidative stress. Rats were fed for four months with either high-fat + sucrose
(HFS) or high-fat + fructose (HFF) or a control diet (C). Half of the HFS or HFF
groups were maintained with the same diet and the other half were switched to the
consumption of C. HFS and HFF groups increased 51% and 19% body weight,
respectively, compared with the C group. Body fat mass, metabolic inflexibility,
glucose intolerance, lipopolysaccharide (LPS), insulin, renal reactive oxygen
species (ROS), malondialdehyde (MDA), Nadphox, and Srebp-1 were significantly
higher and antioxidant enzymes and lean body mass were significantly lower in the
HFS group with respect to the HF-F group. Change in the consumption of HFS or HFF
to a C diet ameliorated the insulin and glucose intolerance. The type of
carbohydrate differentially modified the microbiota composition, however, both
groups significantly decreased C. eutactus with respect to the C group. Thus,
metabolic alterations with the HFS diet had a more detrimental effect than HFF.
PMID- 28420151
TI - Out-of-Plane Continuous Electrostatic Micro-Power Generators.
AB - This paper presents an out-of-plane electrostatic micro-power generator (MPG).
Electret-based continuous MPGs with different gaps and masses are fabricated to
demonstrate the merits of this topology. Experimental results of the MPG
demonstrate output power of 1 mW for a base acceleration amplitude and frequency
of 0.08 g and 86 Hz. The MPGs also demonstrate a wideband harvesting bandwidth
reaching up to 9 Hz. A free-flight and an impact mode model of electrostatic MPGs
are also derived and validated by comparison to experimental results.
PMID- 28420152
TI - Measurement of Pressure Fluctuations inside a Model Thrust Bearing Using PVDF
Sensors.
AB - Thrust bearings play a vital role in propulsion systems. They rely on a thin
layer of oil being trapped between rotating surfaces to produce a low friction
interface. The "quality" of this bearing affects many things from noise
transmission to the ultimate catastrophic failure of the bearing itself. As a
result, the direct measure of the forces and vibrations within the oil filled
interface would be very desirable and would give an indication of the condition
of the bearing in situ. The thickness of the oil film is, however, very small and
conventional vibration sensors are too cumbersome to use in this confined space.
This paper solves this problem by using a piezoelectric polymer film made from
Polyvinylidine Fluoride (PVDF). These films are very thin (50 m) and flexible and
easy to install in awkward spaces such as the inside of a thrust bearing. A model
thrust bearing was constructed using a 3D printer and PVDF films inserted into
the base of the bearing. In doing so, it was possible to directly measure the
force fluctuations due to the rotating pads and investigate various properties of
the thrust bearing itself.
PMID- 28420150
TI - Virtual Reality for Research in Social Neuroscience.
AB - The emergence of social neuroscience has significantly advanced our understanding
of the relationship that exists between social processes and their
neurobiological underpinnings. Social neuroscience research often involves the
use of simple and static stimuli lacking many of the potentially important
aspects of real world activities and social interactions. Whilst this research
has merit, there is a growing interest in the presentation of dynamic stimuli in
a manner that allows researchers to assess the integrative processes carried out
by perceivers over time. Herein, we discuss the potential of virtual reality for
enhancing ecological validity while maintaining experimental control in social
neuroscience research. Virtual reality is a technology that allows for the
creation of fully interactive, three-dimensional computerized models of social
situations that can be fully controlled by the experimenter. Furthermore, the
introduction of interactive virtual characters-either driven by a human or by a
computer-allows the researcher to test, in a systematic and independent manner,
the effects of various social cues. We first introduce key technical features and
concepts related to virtual reality. Next, we discuss the potential of this
technology for enhancing social neuroscience protocols, drawing on illustrative
experiments from the literature.
PMID- 28420153
TI - Health-Related Quality of Life of the General German Population in 2015: Results
from the EQ-5D-5L.
AB - The EQ-5D-5L is a widely used generic instrument to measure health-related
quality of life. This study evaluates health perception in a representative
sample of the general German population from 2015. To compare results over time,
a component analysis technique was used that separates changes in the description
and valuation of health states. The whole sample and also subgroups, stratified
by sociodemographic parameters as well as disease affliction, were analyzed. In
total, 2040 questionnaires (48.4% male, mean age 47.3 year) were included. The
dimension with the lowest number of reported problems was self-care (93.0%
without problems), and the dimension with the highest proportion of impairment
was pain/discomfort (71.2% without problems). Some 64.3% of the study population
were identified as problem-free. The visual analog scale (VAS) mean for all
participants was 85.1. Low education was connected with significantly lower VAS
scores, but the effect was small. Depression, heart disease, and diabetes had a
strong significant negative effect on reported VAS means. Results were slightly
better than those in a similar 2012 survey; the most important driver was the
increase in the share of the study population that reported to be problem-free.
In international comparisons, health perception of the general German population
is relatively high and, compared with previous German studies, fairly stable over
recent years. Elderly and sick people continue to report significant reductions
in perceived health states.
PMID- 28420155
TI - New Compact 3-Dimensional Shape Descriptor for a Depth Camera in Indoor
Environments.
AB - This study questions why existing local shape descriptors have high
dimensionalities (up to hundreds) despite simplicity of local shapes. We derived
an answer from a historical context and provided an alternative solution by
proposing a new compact descriptor. Although existing descriptors can express
complicated shapes and depth sensors have been improved, complex shapes are
rarely observed in an ordinary environment and a depth sensor only captures a
single side of a surface with noise. Therefore, we designed a new descriptor
based on principal curvatures, which is compact but practically useful. For
verification, the CoRBS dataset, the RGB-D Scenes dataset and the RGB-D Object
dataset were used to compare the proposed descriptor with existing descriptors in
terms of shape, instance, and category recognition rate. The proposed descriptor
showed a comparable performance with existing descriptors despite its low
dimensionality of 4.
PMID- 28420154
TI - Mechanisms of LTR-Retroelement Transposition: Lessons from Drosophila
melanogaster.
AB - Long terminal repeat (LTR) retrotransposons occupy a special place among all
mobile genetic element families. The structure of LTR retrotransposons that have
three open reading frames is identical to DNA forms of retroviruses that are
integrated into the host genome. Several lines of evidence suggest that LTR
retrotransposons share a common ancestry with retroviruses and thus are highly
relevant to understanding mechanisms of transposition. Drosophila melanogaster is
an exceptionally convenient model for studying the mechanisms of retrotransposon
movement because many such elements in its genome are transpositionally active.
Moreover, two LTRretrotransposons of D. melanogaster, gypsy and ZAM, have been
found to have infectious properties and have been classified as errantiviruses.
Despite numerous studies focusing on retroviral integration process, there is
still no clear understanding of integration specificity in a target site. Most
LTR retrotransposons non-specifically integrate into a target site. Site
specificity of integration at vertebrate retroviruses is rather relative. At the
same time, sequence-specific integration is the exclusive property of
errantiviruses and their derivatives with two open reading frames. The possible
basis for the errantivirus integration specificity is discussed in the present
review.
PMID- 28420156
TI - A Strain-Based Method to Estimate Slip Angle and Tire Working Conditions for
Intelligent Tires Using Fuzzy Logic.
AB - Tires equipped with sensors, the so-called "intelligent tires", can provide vital
information for control systems, drivers and external users. In this research,
tire dynamic strain characteristics in cornering conditions are collected and
analysed in relation to the variation of tire working conditions, such as
inflation pressure, rolling speed, vertical load and slip angle. An experimental
tire strain-based prototype and an indoor tire test rig are used to demonstrate
the suitability of strain sensors to establish relations between strain data and
lateral force. The results of experiments show that strain values drop sharply
when lateral force is decreasing, which can be used to predict tire slip
conditions. As a first approach to estimate some tire working conditions, such as
the slip angle and vertical load, a fuzzy logic method has been developed. The
simulation and test results confirm the feasibility of strain sensors and the
proposed computational model to solve the non-linearity characteristics of the
tires' parameters and turn tires into a source of useful information.
PMID- 28420157
TI - The Effects of PM2.5 from Asian Dust Storms on Emergency Room Visits for
Cardiovascular and Respiratory Diseases.
AB - A case-crossover study examined how PM2.5 from Asian Dust Storms (ADS) affects
the number of emergency room (ER) admissions for cardiovascular diseases (CVDs)
and respiratory diseases (RDs). Our data indicated that PM2.5 concentration from
ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR)
increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per 10 ug/m3
increase in PM2.5 levels, for CVDs and RDs, respectively. A 10 ug/m3 increase in
PM2.5 from ADSs was significantly associated with an increase in ER visits for
CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for
females (an increase of 3.09 in OR). In contrast, PM2.5 levels had a significant
impact on RD ER visits among those under 65 years of age (OR = 1.77). The risk of
ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the
day after (lag 0 and lag 1); the corresponding risk increase for RDs only
increased on the fifth day after the ADS (lag 5). In Taiwan's late winter and
spring, the severity of ER visits for CVDs and RDs increases. Environmental
protection agencies should employ an early warning system for ADS to reduce high
risk groups' exposure to PM2.5.
PMID- 28420158
TI - Intelligent Medical Garments with Graphene-Functionalized Smart-Cloth ECG
Sensors.
AB - Biopotential signals are recorded mostly by using sticky, pre-gelled electrodes,
which are not ideal for wearable, point-of-care monitoring where the usability of
the personalized medical device depends critically on the level of comfort and
wearability of the electrodes. We report a fully-wearable medical garment for
mobile monitoring of cardiac biopotentials from the wrists or the neck with
minimum restriction to regular clothing habits. The wearable prototype is based
on elastic bands with graphene functionalized, textile electrodes and battery
powered, low-cost electronics for signal acquisition and wireless transmission.
Comparison of the electrocardiogram (ECG) recordings obtained from the wearable
prototype against conventional wet electrodes indicate excellent conformity and
spectral coherence among the two signals.
PMID- 28420159
TI - Expeditious Synthesis of Dianionic-Headed 4-Sulfoalkanoic Acid Surfactants.
AB - 4-Sulfoalkanoic acids are a class of important dianionic-headed surfactants.
Various 4-sulfoalkanoic acids with straight C8, C10, C12, C14, C16, and C18
chains were synthesized expeditiously through the radical addition of methyl 2
((ethoxycarbonothioyl)thio)acetate to linear terminal olefins and subsequent
oxidation with peroxyformic acid. This is a useful and convenient strategy for
the synthesis of dianionic-headed surfactants with a carboxylic acid and sulfonic
acid functionalities in the head group region.
PMID- 28420160
TI - Global Transmission Dynamics of Measles in the Measles Elimination Era.
AB - Although there have been many epidemiological reports of the inter-country
transmission of measles, systematic analysis of the global transmission dynamics
of the measles virus (MV) is limited. In this study, we applied phylogeographic
analysis to characterize the global transmission dynamics of the MV using large
scale genetic sequence data (obtained for 7456 sequences) from 115 countries
between 1954 and 2015. These analyses reveal the spatial and temporal
characteristics of global transmission of the virus, especially in Australia,
China, India, Japan, the UK, and the USA in the period since 1990. The
transmission is frequently observed, not only within the same region but also
among distant and frequently visited areas. Frequencies of export from measles
endemic countries, such as China, India, and Japan are high but decreasing, while
the frequencies from countries where measles is no longer endemic, such as
Australia, the UK, and the USA, are low but slightly increasing. The world is
heading toward measles eradication, but the disease is still transmitted
regionally and globally. Our analysis reveals that countries wherein measles is
endemic and those having eliminated the disease (apart from occasional outbreaks)
both remain a source of global transmission in this measles elimination era. It
is therefore crucial to maintain vigilance in efforts to monitor and eradicate
measles globally.
PMID- 28420161
TI - MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad.
AB - Deregulation of MYC family proteins in cancer is associated with a global
reprogramming of gene expression, ultimately promoting glycolytic pathways, cell
growth, and proliferation. It is well known that MYC upregulation triggers cell
autonomous apoptosis in normal tissues, while frankly malignant cells develop
resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as
inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell
autonomous apoptotic death through an evolutionarily conserved mechanism known as
"cell competition". With regard to this intimate and dual relationship between
MYC and cell death, recent evidence obtained in Drosophila models of cancer has
revealed that, in early tumourigenesis, MYC upregulation guides the clonal
expansion of mutant cells, while the surrounding tissue undergoes non-cell
autonomous death. Apoptosis inhibition in this context was shown to restrain
tumour growth and to restore a wild-type phenotype. This suggests that cell
autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may
shape tumour growth in different ways, soliciting the need to reconsider the role
of cell death in cancer in the light of this new level of complexity. Here we
review recent literature about MYC and cell competition obtained in Drosophila,
with a particular emphasis on the relevance of cell death to cell competition
and, more generally, to cancer. Possible implications of these findings for the
understanding of mammalian cancers are also discussed.
PMID- 28420162
TI - Hepatocyte Growth Factor, a Key Tumor-Promoting Factor in the Tumor
Microenvironment.
AB - The tumor microenvironment plays a key role in tumor development and progression.
Stromal cells secrete growth factors, cytokines and extracellular matrix proteins
which promote growth, survival and metastatic spread of cancer cells. Fibroblasts
are the predominant constituent of the tumor stroma and Hepatocyte Growth Factor
(HGF), the specific ligand for the tyrosine kinase receptor c-MET, is a major
component of their secretome. Indeed, cancer-associated fibroblasts have been
shown to promote growth, survival and migration of cancer cells in an HGF
dependent manner. Fibroblasts also confer resistance to anti-cancer therapy
through HGF-induced epithelial mesenchymal transition (EMT) and activation of pro
survival signaling pathways such as ERK and AKT in tumor cells. Constitutive
HGF/MET signaling in cancer cells is associated with increased tumor
aggressiveness and predicts poor outcome in cancer patients. Due to its role in
tumor progression and therapeutic resistance, both HGF and MET have emerged as
valid therapeutic targets. Several inhibitors of MET and HGF are currently being
tested in clinical trials. Preclinical data provide a strong indication that
inhibitors of HGF/MET signaling overcome both primary and acquired resistance to
EGFR, HER2, and BRAF targeting agents. These findings support the notion that co
targeting of cancer cells and stromal cells is required to prevent therapeutic
resistance and to increase the overall survival rate of cancer patients. HGF
dependence has emerged as a hallmark of therapeutic resistance, suggesting that
inhibitors of biological activity of HGF should be included into therapeutic
regimens of cancer patients.
PMID- 28420163
TI - Beneficial Effects of Melatonin on the In Vitro Maturation of Sheep Oocytes and
Its Relation to Melatonin Receptors.
AB - (1) Background: The binding sites of melatonin, as a multifunctional molecule,
have been identified in human, porcine, and bovine samples. However, the binding
sites and mechanisms of melatonin have not been reported in sheep; (2) Methods:
Cumulus-oocyte complexes (COCs) were cultured in TCM-199 supplemented with
melatonin at concentrations of 0, 10-3, 10-5, 10-7, 10-9, and 10-11 M. Melatonin
receptors (MT1 and MT2) were evaluated via immunofluorescence and Western blot.
The effects of melatonin on cumulus cell expansion, nuclear maturation, embryo
development, and related gene (GDF9, DNMT1, PTX3, HAS2, and EGFR) expression were
investigated. The level of cyclic adenosine monophosphate (cAMP) and cyclic
guanosine monophosphate (cGMP) were evaluated in oocytes and cumulus,
respectively; (3) Results: Both MT1 and MT2 were expressed in oocytes, cumulus
cells, and granulosa cells. Melatonin with a concentration of 10-7 M
significantly enhanced the rates of nuclear maturation, cumulus cells expansion,
cleavage, and blastocyst. Melatonin enhanced the expression of BMP15 in oocytes
and of PTX3, HAS2, and EGFR in cumulus cells. Melatonin decreased the cAMP level
of oocytes but enhanced the cGMP level in oocytes and cumulus cells; (4)
Conclusion: The higher presence of MT1 in GV cumulus cells and the beneficial
effects of melatonin indicated that its roles in regulating sheep oocyte
maturation may be mediated mainly by the MT1 receptor.
PMID- 28420164
TI - The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat
Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral
Adipose-Tissue Function.
AB - Similar to neoplastic tissues, growth and development of adipose tissue are
thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is
associated with development and progression of nonalcoholic fatty liver disease
(NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity
induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a
high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract
ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube
formation in vitro. HFD increased VAT angiogenesis and induced weight gains
including body weight, VAT mass and visceral adipocyte size compared with LFD.
However, HFD-ALS led to weight reductions without affecting calorie intake
compared with HFD. HFD-ALS also reduced serum ALT and AST levels and improved
lipid metabolism. HFD-ALS suppressed steatosis, infiltration of inflammatory
cells, and accumulation of collagen in livers. HFD-ALS modulated hepatic
expression of genes involved in lipid metabolism, inflammation, fibrosis,
antioxidation, and apoptosis. Concomitantly, analysis of VAT function revealed
that HFD-ALS led to fewer CD68-positive macrophage numbers and lower expression
of inflammatory cytokines compared with HFD. Our findings show that the anti
angiogenic herbal extract ALS-L1023 attenuates NAFLD by targeting VAT during
obesity, suggesting that angiogenesis inhibitors could aid in the treatment and
prevention of obesity-induced human NAFLD.
PMID- 28420165
TI - Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of
Intestinal Polyps in Min Mice.
AB - Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes
the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and
its inhibitor is reported to reduce cancer cell proliferation and induce
apoptosis. Therefore, we asked whether acetazolamide, a CA inhibitor, could
inhibit intestinal carcinogenesis. Five-week-old male Apc-mutant mice, Min mice,
were fed a AIN-76A diet containing 200 or 400 ppm acetazolamide. As a result,
acetazolamide treatment reduced the total number of intestinal polyps by up to
50% compared to the control group. In addition, the acetazolamide-treated group
had low cell proliferation and a high apoptosis ratio in the intestinal polyp
epithelial cells. Moreover, the mRNA expression level of proinflammatory
cytokines, such as IL-6, involved in the cell proliferation was decreased in the
polyp part of the acetazolamide-treated group. Next, we examined the effects of
acetazolamide on the activation of several transcriptional factors (AP-1, HIF,
HSF, NF-kappaB, NRF2, p53, and STAT3) using a reporter gene assay in human colon
cancer cells, Caco-2 cells. Among the examined transcriptional factors, NRF2
transcriptional activation was strongly induced. NRF2-targeting genes, gammaGCS,
GPx1, HO-1, and NQO-1, were also elevated in the intestinal polyps of
acetazolamide-treated Min mice. Our results suggested that CA is involved in
intestinal carcinogenesis. Acetazolamide could inhibit polyp formation through
suppressing local/general cytokine levels, i.e., IL-6, via NRF2 activation.
PMID- 28420166
TI - Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via
Regulation of TLR4 and PPAR-gamma Dependent on PI3K/Akt/mTOR Signal Pathway.
AB - Endothelial lesion response to injurious stimuli is a necessary step for
initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from
different marine sources is shown to exhibit anti-inflammatory properties.
However, the potential roles and possible molecular mechanisms of Hy in
endothelial inflammation have yet to be fully clarified. We showed that Hy
significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro
inflammatory cytokines expressions, including tumor necrosis factor-alpha (TNF
alpha), interleukin-1beta (IL-1beta), monocyte chemoattractant protein 1 (MCP-1)
and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the
phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome
proliferator-activated receptor gamma (PPAR-gamma) and upregulated toll-like
receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented
by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4
expressions and decreases in PPAR-gamma levels. Genetic silencing of TLR4 or PPAR
gamma agonist pioglitazone obviously abrogated the levels of pro-inflammatory
cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert
anti-inflammatory actions through the regulation of TLR4 and PPAR-gamma dependent
on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent
that can potentially relieve or ameliorate endothelial inflammation-associated
diseases.
PMID- 28420167
TI - Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to
Factor VIII/IX.
AB - The development of alloantibodies neutralising therapeutically administered
factor (F) VIII/IX (inhibitors) is currently the most severe complication of the
treatment of haemophilia. When persistent and at a high titre, inhibitors
preclude the standard replacement treatment with FVIII/FIX concentrates, making
patients' management challenging. Indeed, the efficacy of bypassing agents, i.e.,
activated prothrombin complex concentrates (aPCC) and recombinant activated
factor VII (rFVIIa), needed to overcome the haemostatic interference of the
inhibitor, is not comparable to that of factor concentrates. In addition, the
therapeutical response is unpredictable, with a relevant inter-individual and
even intra-individual variability, and no laboratory assay is validated to
monitor the efficacy and safety of the treatment. As a result, inhibitor patients
have a worse joint status and quality of life compared to inhibitor-free subjects
and the eradication of the inhibitor by immune tolerance induction is the
preeminent therapeutic goal, particularly in children. However, over the last
decades, treatment with bypassing agents has been optimised, allowing home
treatment and the individualisation of regimens aimed at improving clinical
outcomes. In this respect, a growing body of evidence supports the efficacy of
prophylaxis with both bypassing agents in reducing bleeding rates and improving
the quality of life, although the impact on long-term outcomes (in particular on
preventing/reducing joint deterioration) is still unknown. This review offers an
update on the current knowledge and practice of the use of bypassing agents in
haemophiliacs with inhibitors, as well as on debated issues and unmet needs in
this challenging setting.
PMID- 28420168
TI - Comparative Study of Blood-Based Biomarkers, alpha2,3-Sialic Acid PSA and PHI,
for High-Risk Prostate Cancer Detection.
AB - Prostate Specific Antigen (PSA) is the most commonly used serum marker for
prostate cancer (PCa), although it is not specific and sensitive enough to allow
the differential diagnosis of the more aggressive tumors. For that, new
diagnostic methods are being developed, such as PCA-3, PSA isoforms that have
resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms.
In the present study, we have compared the PHI with our recently developed PSA
glycoform assay, based on the determination of the alpha2,3-sialic acid
percentage of serum PSA (% alpha2,3-SA), in a cohort of 79 patients, which
include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH)
patients. The % alpha2,3-SA could distinguish high-risk PCa patients from the
rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs.
0.840), although the PHI correlated better with the Gleason score than the %
alpha2,3-SA. The combination of both markers increased the AUC up to 0.985
resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk
PCa from the other low and intermediate-risk PCa and BPH patients. These results
suggest that both serum markers complement each other and offer an improved
diagnostic tool to identify high-risk PCa, which is an important requirement for
guiding treatment decisions.
PMID- 28420169
TI - Ultrasensitive Label-Free Sensing of IL-6 Based on PASE Functionalized Carbon
Nanotube Micro-Arrays with RNA-Aptamers as Molecular Recognition Elements.
AB - This study demonstrates the rapid and label-free detection of Interleukin-6 (IL
6) using carbon nanotube micro-arrays with aptamer as the molecular recognition
element. Single wall carbon nanotubes micro-arrays biosensors were manufactured
using photo-lithography, metal deposition, and etching techniques. Nanotube
biosensors were functionalized with 1-Pyrenebutanoic Acid Succinimidyl Ester
(PASE) conjugated IL-6 aptamers. Real time response of the sensor conductance was
monitored with increasing concentration of IL-6 (1 pg/mL to 10 ng/mL), exposure
to the sensing surface in buffer solution, and clinically relevant spiked blood
samples. Non-specific Bovine Serum Albumin (BSA), PBS samples, and anti-IgG
functionalized devices gave similar signatures in the real time conductance
versus time experiments with no significant change in sensor signal. Exposure of
the aptamer functionalized nanotube surface to IL-6 decreased the conductance
with increasing concentration of IL-6. Experiments based on field effect
transistor arrays suggested shift in drain current versus gate voltage for 1 pg
and 1 ng of IL-6 exposure. Non-specific BSA did not produce any appreciable shift
in the Ids versus Vg suggesting specific interactions of IL-6 on PASE conjugated
aptamer surface gave rise to the change in electrical signal. Both Z axis and
phase image in an Atomic Force Microscope (AFM) suggested unambiguous molecular
interaction of the IL-6 on the nanotube-aptamer surface at 1 pg/mL concentration.
The concentration of 1 pg falls below the diagnostic gray zone for cancer (2.3 pg
4 ng/mL), which is an indicator of early stage cancer. Thus, nanotube micro
arrays could potentially be developed for creating multiplexed assays involving
cancer biomarker proteins and possibly circulating tumor cells all in a single
assay using PASE functionalization protocol.
PMID- 28420170
TI - Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive
Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1
and MAPK Signaling in PC12 Cells.
AB - BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and
exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However,
high concentration of fisetin is reported to produce reactive oxygen species
(ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer
cells. The aim of this study is to investigate the cytoprotective effects of low
concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in
neuronal-like catecholaminergic PC12 cells. METHODS: Cell viability was assayed
by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and
apoptotic and autophagic markers were analyzed by Western blot. Gene expression
of unfolded protein response (UPR) and Phase II enzymes was further investigated
using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using
2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The
effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1
(Sirtuin 1) signaling pathways were examined using Western blotting and specific
inhibitors. RESULTS: Fisetin (<20 uM) restored cell viability and repressed
apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated
Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78
(GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles
homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2
targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and
cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of
Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal
regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK.
Addition of JNK and p38 MAPK inhibitor significantly antagonized its
cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm
inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor)
significantly blocked fisetin-mediated cytoprotection. In conclusion, this result
shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive
cellular stress response pathways so as to protect cells from Tm-induced
cytotoxicity.
PMID- 28420171
TI - Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function.
AB - The three major blood cell types, i.e., platelets, erythrocytes and leukocytes,
are all produced in the bone marrow. While red blood cells are the most numerous
and white cells are the largest, platelets are small fragments and account for a
minor part of blood volume. However, platelets display a crucial function by
preventing bleeding. Upon vessel wall injury, platelets adhere to exposed
extracellular matrix, become activated, and form a platelet plug preventing
hemorrhagic events. However, when platelet activation is exacerbated, as in
rupture of an atherosclerotic plaque, the same mechanism may lead to acute
thrombosis causing major ischemic events such as myocardial infarction or stroke.
In the past few years, major progress has been made in understanding of platelet
function modulation. In this respect, membrane channels formed by connexins
and/or pannexins are of particular interest. While it is still not completely
understood whether connexins function as hemichannels or gap junction channels to
inhibit platelet aggregation, there is clear-cut evidence for a specific
implication of pannexin1 channels in collagen-induced aggregation. The focus of
this review is to summarize current knowledge of the role of connexins and
pannexins in platelet aggregation and to discuss possible pharmacological
approaches along with their limitations and future perspectives for new potential
therapies.
PMID- 28420173
TI - Transcriptome Sequencing of Dianthus spiculifolius and Analysis of the Genes
Involved in Responses to Combined Cold and Drought Stress.
AB - Dianthus spiculifolius, a perennial herbaceous flower and a member of the
Caryophyllaceae family, has strong resistance to cold and drought stresses. To
explore the transcriptional responses of D. spiculifolius to individual and
combined stresses, we performed transcriptome sequencing of seedlings under
normal conditions or subjected to cold treatment (CT), simulated drought
treatment (DT), or their combination (CTDT). After de novo assembly of the
obtained reads, 112,015 unigenes were generated. Analysis of differentially
expressed genes (DEGs) showed that 2026, 940, and 2346 genes were up-regulated
and 1468, 707, and 1759 were down-regulated in CT, DT, and CTDT samples,
respectively. Among all the DEGs, 182 up-regulated and 116 down-regulated genes
were identified in all the treatment groups. Analysis of metabolic pathways and
regulatory networks associated with the DEGs revealed overlaps and cross-talk
between cold and drought stress response pathways. The expression profiles of the
selected DEGs in CT, DT, and CTDT samples were characterized and confirmed by
quantitative RT-PCR. These DEGs and metabolic pathways may play important roles
in the response of D. spiculifolius to the combined stress. Functional
characterization of these genes and pathways will provide new targets for
enhancement of plant stress tolerance through genetic manipulation.
PMID- 28420174
TI - An Expedient Total Synthesis of Triciribine.
AB - In the present paper, we report an expedient total synthesis of triciribine, a
tricyclic 7-deazapurine nucleoside and protein kinase B (AKT ) inhibitor, in 35%
overall yield. Our synthesis route features a highly regioselective substitution
of 1-N-Boc-2-methylhydrazine and a trifluoroacetic acid catalyzed one-pot
transformation which combined the deprotection of the tert-butylcarbonyl (Boc)
group and ring closure reaction together to give a tricyclic nucleobase motif.
PMID- 28420172
TI - Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always
Necessary?
AB - Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most
common subtypes of primary aldosteronism (PA) that require targeted and distinct
therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with
mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society
Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish
between unilateral and bilateral aldosterone overproduction and therefore, to
safely refer patients with PA to surgery. Despite significant advances in the
optimization of the AVS procedure and the interpretation of hormonal data, a
standardized protocol across centers is still lacking. Alternative methods are
sought to either localize an aldosterone producing adenoma or to predict the
presence of unilateral disease and thereby substantially reduce the number of
patients with PA who proceed to AVS. In this review, we summarize the recent
advances in subtyping PA for the diagnosis of unilateral and bilateral disease.
We focus on the developments in the AVS procedure, the interpretation criteria,
and comparisons of the performance of AVS with the alternative methods that are
currently available.
PMID- 28420175
TI - A New Input Device for Spastics Based on Strain Gauge.
AB - This article presents a new sensor for use by people with spastic disorders and
similar conditions and enables them to steer and control medical devices such as
electric powered wheelchairs. As spastic patients often suffer from cramping of
their extremities, which can then no longer be controlled, using a standard
joystick while operating a powered wheelchair can lead to dangerous situations.
To prevent this, we designed a sensor based on strain gauges, which is shaped
like a flat disc that can be operated using any body part. By shifting weight
along the x- and y-axis, the disc tilts in all directions thereby generating
proportionate output signals. The disc can also be pressed downward (z-axis), for
example, to open a wheelchair's menu. Thanks to the sensor's flat disc-like
construction and the option of mounting it into a control panel, users are not in
danger of becoming stuck on the disc during spastic episodes. In the event of a
spasm, body parts simply slide over the disc reducing risk of unintended actions.
The sensor is adaptive and adjustable enabling it to fit a user's range of
strength and motion at any time. It was developed to ensure users can operate
sensitive systems safely.
PMID- 28420176
TI - Establishing Reliable Cu-64 Production Process: From Target Plating to Molecular
Specific Tumor Micro-PET Imaging.
AB - Copper-64 is a useful radioisotope for positron emission tomography (PET). Due to
the wide range of applications, the demand of 64Cu with low metallic impurities
is increasing. Here we report a simple method for the efficient production of
high specific activity 64Cu using a cyclotron for biomedical application. We
designed new equipment based on the plating of enriched 64Ni as the target, and
used automated ion exchange chromatography to purify copper-64 efficiently after
irradiation and dissolution of the target in good radiochemical and chemical
yield and purity. The 64Cu radionuclide produced using 99.32% enriched 64Ni with
a density of 61.4 +/- 5.0 mg/cm2, reaching a total radioactivity greater than 200
mCi, with specific activity up to 5.6 GBq/MUmoL. It was further incorporated into
modified monoclonal antibody DOTA-rituximab to synthesize 64Cu-DOTA-rituximab,
which was used successfully for micro-PET imaging.
PMID- 28420178
TI - How Older Adults and Their Families Perceive Family Talk about Aging-Related EOL
Issues: A Dialectical Analysis.
AB - For older adults, approaching end-of-life (EOL) brings unique transitions related
to family relationships. Unfortunately, most families greatly underestimate the
need to discuss these difficult issues. For example, parents approaching EOL
issues often struggle with receiving assistance from others, avoiding family
conflict, and maintaining their sense of personhood. In addition, discussions of
EOL issues force family members to face their parents' mortality, which can be
particularly difficult for adult children to process emotionally. This study
explored aging issues identified by aging parents and their families as they
traverse these impending EOL changes. Ten focus groups of seniors (n = 65) were
conducted. Focus groups were organized according to race (African
American/European-American), gender, and whether the older adult was living
independently or in an assisted care facility. When asked open-ended questions
about discussing aging and EOL issues with family members, participants revealed
tensions that led us to consider Relational Dialectics Theory as a framework for
analysis. The predominant tension highlighted in this report was certainty versus
uncertainty, with the two sub-themes of sustained life versus sustained
personhood and confronting versus avoiding EOL issues. For these data, there were
more similarities than differences as a result of gender, race, or living
situation than one might expect, although culture and financial status were found
to be influential in the avoidance of EOL discussions. The results of this study
help to provide additional insight into relational dialectics related to aging,
EOL, and the importance of communication in facilitating family coping.
PMID- 28420177
TI - Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone
Motif-Fused 3,3'-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition
Reaction.
AB - Described herein is the development of a facile and efficient methodology for the
synthesis of novel turmerone motif-fused 3,3'-pyrrolidinyl-dispirooxindoles 3-5
via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine
ylides (thermally generated in situfrom isatins and proline or thioproline or
sarcosine). Products bearing four or three consecutive stereocenters consist of
two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary
stereocenters fused in one ring structure were smoothly obtained in high yields
(up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable
application of this method was for the design of new hybrid architectures for
biological screening through the adequate fusion of these sub-units of turmerone
and 3,3'-pyrrolidinyl-dispirooxindole, generating drug-like molecules.
PMID- 28420179
TI - Systematic Understanding of the Mechanism of Salvianolic Acid A via Computational
Target Fishing.
AB - Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent
anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A
systematic overview of its mechanism of action is yet to be performed. In the
present study, the druggability of SAA was measured using the TCMSP server, and
potential targets of SAA were identified by PharmMapper and DRAR-CPI.
Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and
drug-target-pathway networks were constructed to give a visual view. The results
showed that SAA has good druggability, and 13 putative protein targets were
identified. Network analysis showed that these targets were associated with
cancer, metabolism and other physiological processes. In summary, SAA is
predicted to target multiple proteins and pathways to form a network that exerts
systematic pharmacological effects.
PMID- 28420180
TI - Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid
Podophyllotoxin Conjugate towards Human Gastric Cancer Cells.
AB - With the purpose of creating a multifunctional drug for gastric cancer treatment,
a novel all-trans-retinoic acid (ATRA) conjugate with podophyllotoxin (PPT) was
designed and synthesized, and its in vitro antiproliferative activity was
evaluated against human gastric cancer cell lines using CCK-8 assay. The
conjugate, P-A, exhibited significant anticancer activity against MKN-45 and BGC
823 cells with IC50 values of 0.419 +/- 0.032 and 0.202 +/- 0.055 MUM,
respectively. Moreover, P-A efficiently triggered cell cycle arrest and induced
apoptosis in MKN-45 and BGC-823 cells due to modulation of cell cycle arrest-
(CDK1, CDK2, CyclinA and CyclinB1) and apoptosis- (cleaved caspase-3, -8 and -9)
related proteins, respectively. Further mechanism studies revealed that P-A could
increase the expression levels of RARalpha and RARbeta, and decrease the level of
RARgamma in MKN-45 and BGC-823 cells. Finally, P-A inhibited the ERK1/2 and AKT
signaling in the above two cancer cell lines. More importantly, the underlying
mechanisms of P-A were similar to those of precursor PPT but different with the
other precursor ATRA. Together, the conjugate P-A was a promising candidate for
the potential treatment of human gastric cancer.
PMID- 28420182
TI - Nanoscale in Photocatalysis.
AB - n/a.
PMID- 28420181
TI - Comment on Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies. Toxins
2016, 8, 358.
AB - Recently, the clinical and experimental evidences that support the toxic effects
of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD)
patients, has been discussed. In this panorama, the authors described several in
vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the
pathogenesis of low turnover bone disease. However, the discussion claims the
need for relevant clinical studies in CKD patients whose bone turnover biomarkers
and bone histomorphometry were assessed in order to demonstrate the association
between serum levels of indoxyl sulfate and bone turnover. We would like to
underline the availability of this clinical data to support the concept that
indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease
in CKD patients.
PMID- 28420183
TI - Anti-Proliferative Effect of Triterpenoidal Glycosides from the Roots of Anemone
vitifolia through a Pro-Apoptotic Way.
AB - A cytotoxicity-guided phytochemical investigation of Anemone vitifolia roots led
to the isolation of six oleanane saponins (1-6), which were reported from the
species for the first time. Their structures were determined by comparing its MS
and NMR data with those in literature. Compounds 1-4 showed significant
inhibitory effects on the proliferation of hepatocellular carcinoma HepG2 cells
with IC50 values ranging from 2.0 to 8.5 MUM, compared to positive control
methotrexate with IC50 value of 15.8 MUM. Flow cytometry analysis revealed that
compounds 1-4 exerted anti-proliferative effects through a pro-apoptotic way of
hepatocellular carcinoma cells.
PMID- 28420184
TI - Metajapogenins A-C, Pregnane Steroids from Shells of Metaplexis japonica.
AB - Phytochemical investigation of the shells of Metaplexis japonica (Thunb.) Makino,
belonging to the family of Apocynaceae, afforded three new pregnane steroids,
metajapogenins A-C, along with three known compounds. The structures of the new
compounds were elucidated as 12beta,14beta,17beta-trihydroxypregna-3,5-dien-7,20
dione, 12beta,14beta,17beta,20beta-tetrahydroxypregna-3,5-dien-7-one;
3beta,12beta,14beta,17beta-tetrahydroxypregn-5-ene-7,20-dione on the basis of
extensive spectroscopic evidence derived from 1D; 2D-NMR experiments and mass
spectrometry. The known compounds included pergularin; 12-O-acetylpergularin; and
pergularin-3-O-beta-d-oleandropyranose; which were identified for the first time
in the shells of M. japonica.
PMID- 28420186
TI - Using Moss to Assess Airborne Heavy Metal Pollution in Taizhou, China.
AB - Bryophytes act as bioindicators and bioaccumulators of metal deposition in the
environment. To understand the atmospheric deposition of heavy metals (cadmium
(Cd), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc
(Zn)) in Taizhou, East China, samples of moss (Haplocladium microphyllum) were
collected from 60 sites selected by a systematic sampling method during the
summer of 2012, and the concentrations of these heavy metals were determined by
inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results
suggested that the concentrations of these metals varied moderately among
different sites, indicating a similar contamination level for each element
throughout the monitoring region. The mean values under investigation were higher
than those from neighboring cities, such as Wuxi, Xuzhou, and Nanjing, and much
higher than those in Europe based on a 2010 survey. Significant (p < 0.01)
correlations were identified among some of the heavy metals, suggesting that
these originated from identical sources. There was no statistically significant
correlation between Hg and all the other elements. Spatial distribution maps of
the elements over the sampled territory were created using Arc-GIS 9.0. The
potential ecological risk index indicated that the air was heavily polluted by Cd
and Hg, and that there was a considerable potential ecological risk from all the
heavy metals studied.
PMID- 28420187
TI - Device-Free Localization via an Extreme Learning Machine with Parameterized
Geometrical Feature Extraction.
AB - Device-free localization (DFL) is becoming one of the new technologies in
wireless localization field, due to its advantage that the target to be localized
does not need to be attached to any electronic device. In the radio-frequency
(RF) DFL system, radio transmitters (RTs) and radio receivers (RXs) are used to
sense the target collaboratively, and the location of the target can be estimated
by fusing the changes of the received signal strength (RSS) measurements
associated with the wireless links. In this paper, we will propose an extreme
learning machine (ELM) approach for DFL, to improve the efficiency and the
accuracy of the localization algorithm. Different from the conventional machine
learning approaches for wireless localization, in which the above differential
RSS measurements are trivially used as the only input features, we introduce the
parameterized geometrical representation for an affected link, which consists of
its geometrical intercepts and differential RSS measurement. Parameterized
geometrical feature extraction (PGFE) is performed for the affected links and the
features are used as the inputs of ELM. The proposed PGFE-ELM for DFL is trained
in the offline phase and performed for real-time localization in the online
phase, where the estimated location of the target is obtained through the created
ELM. PGFE-ELM has the advantages that the affected links used by ELM in the
online phase can be different from those used for training in the offline phase,
and can be more robust to deal with the uncertain combination of the detectable
wireless links. Experimental results show that the proposed PGFE-ELM can improve
the localization accuracy and learning speed significantly compared with a number
of the existing machine learning and DFL approaches, including the weighted K
nearest neighbor (WKNN), support vector machine (SVM), back propagation neural
network (BPNN), as well as the well-known radio tomographic imaging (RTI) DFL
approach.
PMID- 28420188
TI - Health Risk Assessment of Indoor Air Quality, Socioeconomic and House
Characteristics on Respiratory Health among Women and Children of Tirupur, South
India.
AB - Background: Indoor air pollution is still considered as one of the leading causes
of morbidity and mortality worldwide and especially in developing countries,
including India. This study aims to assess social, housing, and indoor
environmental factors associated with respiratory health among mothers and
children. Methods: The study was conducted in the city of Tirupur, South India.
We quantitatively assessed the indoor exposure to fine particulate matter (PM2.5)
and carbon monoxide in relation to respiratory health among women and children.
Information on health status, household characteristics and socioeconomic factors
was collected using a modified standardised questionnaire. Results: This study
demonstrates the significant health impact of housing and socioeconomic
characteristics on the burden of respiratory illness among women and children in
urban South India. Increased respiratory symptoms were recorded among women and
children from low income households, and those who allowed smoking inside. The
mean PM2.5 concentration measured in this study was 3.8 mg/m3 which exceeded the
World Health Organization (WHO) 24 h guideline value of 0.025 mg/m3. Conclusions:
This study is the first to our knowledge carried out in urban South India and the
findings can be used for future intervention studies.
PMID- 28420189
TI - Demographic and Environmental Factors Associated with Mental Health: A Cross
Sectional Study.
AB - Relevant demographic and environmental conditions need to be understood before
tailoring policies to improve mental health. Using community health survey data
from 25 communities in Seoul, 2013, cross-sectional associations between mental
health and community level environments were assessed. Mental health outcomes
(self-rated stress levels (SRS) and depressive symptoms (DS)) were analyzed.
Community environmental factors included green space, green facilities, and
annual PM10 level (AnnPM10); socio-demographic factors included sex, age,
education, labor market participation, comorbidity, sleep hours, physical
activity, smoking, and drinking. A total of 23,139 people with the following
characteristics participated: men (44.2%); age groups 19-39 (36.0%), 40-59
(39.4%), 60-74 (19.2%), and 75+ (5.4%). Women had higher odds ratios (OR) for SRS
[OR 1.22, 95% Confidence interval (CI) 1.17-1.27] and DS [OR 1.55, 95% CI 1.42
1.71]. Regular physical activity predicted SRS [OR 0.90, 95% CI 0.84-0.95] and DS
[OR 0.98, 95% CI 0.88-1.10]; current smoking and drinking were adversely
associated with both SRS and DS. Higher accessibility to green space (Q4) was
inversely associated with DS [OR 0.89, 95% CI 0.81-0.97] compared to lower
accessibility (Q1). AnnPM10, annual levels for particles of aerodynamic diameter
<10 um (PM10), among communities was associated with poorer SRS [OR 1.02, 95% CI
1.00-1.04] by 10 MUg/m3 increases. Therefore, both demographic and environmental
factors should be considered to understand mental health conditions among the
general population.
PMID- 28420190
TI - Overexpression of S-Adenosyl-l-Methionine Synthetase 2 from Sugar Beet M14
Increased Arabidopsis Tolerance to Salt and Oxidative Stress.
AB - The sugar beet monosomic addition line M14 is a unique germplasm that contains
genetic materials from Beta vulgaris L. and Beta corolliflora Zoss, and shows
tolerance to salt stress. Our study focuses on exploring the molecular mechanism
of the salt tolerance of the sugar beet M14. In order to identify differentially
expressed genes in M14 under salt stress, a subtractive cDNA library was
generated by suppression subtractive hybridization (SSH). A total of 36 unique
sequences were identified in the library and their putative functions were
analyzed. One of the genes, S-adenosylmethionine synthetase (SAMS), is the key
enzyme involved in the biosynthesis of S-adenosylmethionine (SAM), a precursor of
polyamines. To determine the potential role of SAMS in salt tolerance, we
isolated BvM14-SAMS2 from the salt-tolerant sugar beet M14. The expression of
BvM14-SAMS2 in leaves and roots was greatly induced by salt stress.
Overexpression of BvM14-SAMS2 in Arabidopsis resulted in enhanced salt and H2O2
tolerance. Furthermore, we obtained a knock-down T-DNA insertion mutant of
AtSAMS3, which shares the highest homology with BvM14-SAMS2. Interestingly, the
mutant atsam3 showed sensitivity to salt and H2O2 stress. We also found that the
antioxidant system and polyamine metabolism play an important role in salt and
H2O2 tolerance in the BvM14-SAMS2-overexpressed plants. To our knowledge, the
function of the sugar beet SAMS has not been reported before. Our results have
provided new insights into SAMS functions in sugar beet.
PMID- 28420191
TI - Designing Effective Interactions for Concordance around End-of-Life Care
Decisions: Lessons from Hospice Admission Nurses.
AB - Near the end of life, hospice care reduces symptom-related distress and
hospitalizations while improving caregiving outcomes. However, it takes time for
a person to gain a sufficient understanding of hospice and decide to enroll. This
decision is influenced by knowledge of hospice and its services, emotion and
fear, cultural and religious beliefs, and an individual's acceptance of
diagnosis. Hospice admission interactions, a key influence in shaping decisions
regarding hospice care, happen particularly late in the illness trajectory and
are often complex, unpredictable, and highly variable. One goal of these
interactions is ensuring patients and families have accurate and clear
information about hospice care to facilitate informed decisions. So inconsistent
are practices across hospices in consenting patients that a 2016 report from the
Office of Inspector General (OIG) entitled "Hospices should improve their
election statements and certifications of terminal illness" called for complete
and accurate election statements to ensure that hospice patients and their
caregivers can make informed decisions and understand the costs and benefits of
choosing hospice care. Whether complete and accurate information at initial
admission visits improves interactions and outcomes is unknown. Our recent
qualitative work investigating interactions between patients, caregivers, and
hospice nurses has uncovered diverse and often diverging stakeholder-specific
expectations and perceptions which if not addressed can create discordance and
inhibit decision-making. This paper focuses on better understanding the
communication dynamics and practices involved in hospice admission interactions
in order to design more effective interactions and support the mandate from the
OIG to provide hospice patients and their caregivers with accurate and complete
information. This clarity is particularly important when discussing the non
curative nature of hospice care, and the choice patients make to forego
aggressive treatment measures when they enroll in hospice. In a literal sense, to
enroll in hospice means to bring in support for end-of-life care. It means to
identify the need for expertise around symptom management at end-of-life, and
agree to having a care team come and manage someone's physical, psychosocial,
and/or spiritual needs. As with all care, hospice can be stopped if it is no
longer considered appropriate. To uncover the communication tensions undergirding
a hospice admission interaction, we use Street's ecological theory of patient
centered communication to analyze a case exemplar of a hospice admission
interaction. This analysis reveals diverse points of struggle within hospice
decision-making processes around hospice care and the need for communication
techniques that promote trust and acceptance of end-of-life care. Lessons learned
from talking about hospice care can inform other quality initiatives around
communication and informed decision-making in the context of advance care
planning, palliative care, and end-of-life care.
PMID- 28420185
TI - Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation,
Progression and Metastasis.
AB - There is highly credible evidence that melatonin mitigates cancer at the
initiation, progression and metastasis phases. In many cases, the molecular
mechanisms underpinning these inhibitory actions have been proposed. What is
rather perplexing, however, is the large number of processes by which melatonin
reportedly restrains cancer development and growth. These diverse actions suggest
that what is being observed are merely epiphenomena of an underlying more
fundamental action of melatonin that remains to be disclosed. Some of the
arresting actions of melatonin on cancer are clearly membrane receptor-mediated
while others are membrane receptor-independent and involve direct intracellular
actions of this ubiquitously-distributed molecule. While the emphasis of
melatonin/cancer research has been on the role of the indoleamine in restraining
breast cancer, this is changing quickly with many cancer types having been shown
to be susceptible to inhibition by melatonin. There are several facets of this
research which could have immediate applications at the clinical level. Many
studies have shown that melatonin's co-administration improves the sensitivity of
cancers to inhibition by conventional drugs. Even more important are the findings
that melatonin renders cancers previously totally resistant to treatment
sensitive to these same therapies. Melatonin also inhibits molecular processes
associated with metastasis by limiting the entrance of cancer cells into the
vascular system and preventing them from establishing secondary growths at
distant sites. This is of particular importance since cancer metastasis often
significantly contributes to death of the patient. Another area that deserves
additional consideration is related to the capacity of melatonin in reducing the
toxic consequences of anti-cancer drugs while increasing their efficacy. Although
this information has been available for more than a decade, it has not been
adequately exploited at the clinical level. Even if the only beneficial actions
of melatonin in cancer patients are its ability to attenuate acute and long-term
drug toxicity, melatonin should be used to improve the physical wellbeing of the
patients. The experimental findings, however, suggest that the advantages of
using melatonin as a co-treatment with conventional cancer therapies would far
exceed improvements in the wellbeing of the patients.
PMID- 28420192
TI - Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after
Subarachnoid Haemorrhage.
AB - Early brain injury (EBI) is considered to be the major factor associated with
high morbidity and mortality after subarachnoid haemorrhage (SAH). Apoptosis is
the major pathological mechanism of EBI, and its pathogenesis has not been fully
clarified. Here, we report that thioredoxin-interacting protein (TXNIP), which is
induced by protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK),
participates in EBI by promoting apoptosis. By using adult male Sprague-Dawley
rats to establish SAH models, as well as Terminal dexynucleotidyl transferase
(TdT)-mediated dUTP nick end labeling (TUNEL) staining, immunofluorescence, and
western blot, we found that TXNIP expression significantly increased after SAH in
comparison to the sham group and peaked at 48 h (up to 3.2-fold). Meanwhile,
TXNIP was widely expressed in neurons and colocalized with TUNEL-positive cells
in the hippocampus and cortex of SAH rats. After administration of TXNIP
inhibitor-resveratrol (60 mg/kg), TXNIP small interfering RNA (siRNA) and the
PERK inhibitor GSK2656157, TXNIP expression was significantly reduced,
accompanied by an attenuation of apoptosis and prognostic indicators, including
SAH grade, neurological deficits, brain water content, and blood-brain barrier
(BBB) permeability. Collectively, these results suggest that TXNIP may
participate in EBI after SAH by mediating apoptosis. The blockage of TXNIP
induced by PERK could be a potential therapeutic strategy for SAH treatment.
PMID- 28420193
TI - A Quantitative PCR-Electrochemical Genosensor Test for the Screening of Biotech
Crops.
AB - The design of screening methods for the detection of genetically modified
organisms (GMOs) in food would improve the efficiency in their control. We report
here a PCR amplification method combined with a sequence-specific electrochemical
genosensor for the quantification of a DNA sequence characteristic of the 35S
promoter derived from the cauliflower mosaic virus (CaMV). Specifically, we
employ a genosensor constructed by chemisorption of a thiolated capture probe and
p-aminothiophenol gold surfaces to entrap on the sensing layer the unpurified PCR
amplicons, together with a signaling probe labeled with fluorescein. The proposed
test allows for the determination of a transgene copy number in both hemizygous
(maize MON810 trait) and homozygous (soybean GTS40-3-2) transformed plants, and
exhibits a limit of quantification of at least 0.25% for both kinds of GMO lines.
PMID- 28420194
TI - Multiple Objects Fusion Tracker Using a Matching Network for Adaptively
Represented Instance Pairs.
AB - Multiple-object tracking is affected by various sources of distortion, such as
occlusion, illumination variations and motion changes. Overcoming these
distortions by tracking on RGB frames, such as shifting, has limitations because
of material distortions caused by RGB frames. To overcome these distortions, we
propose a multiple-object fusion tracker (MOFT), which uses a combination of 3D
point clouds and corresponding RGB frames. The MOFT uses a matching function
initialized on large-scale external sequences to determine which candidates in
the current frame match with the target object in the previous frame. After
conducting tracking on a few frames, the initialized matching function is fine
tuned according to the appearance models of target objects. The fine-tuning
process of the matching function is constructed as a structured form with diverse
matching function branches. In general multiple object tracking situations, scale
variations for a scene occur depending on the distance between the target objects
and the sensors. If the target objects in various scales are equally represented
with the same strategy, information losses will occur for any representation of
the target objects. In this paper, the output map of the convolutional layer
obtained from a pre-trained convolutional neural network is used to adaptively
represent instances without information loss. In addition, MOFT fuses the
tracking results obtained from each modality at the decision level to compensate
the tracking failures of each modality using basic belief assignment, rather than
fusing modalities by selectively using the features of each modality.
Experimental results indicate that the proposed tracker provides state-of-the-art
performance considering multiple objects tracking (MOT) and KITTIbenchmarks.
PMID- 28420195
TI - Carbon Nanotube-Based Chemiresistive Sensors.
AB - The development of simple and low-cost chemical sensors is critically important
for improving human life. Many types of chemical sensors have been developed.
Among them, the chemiresistive sensors receive particular attention because of
their simple structure, the ease of high precise measurement and the low cost.
This review mainly focuses on carbon nanotube (CNT)-based chemiresistive sensors.
We first describe the properties of CNTs and the structure of CNT chemiresistive
sensors. Next, the sensing mechanism and the performance parameters of the
sensors are discussed. Then, we detail the status of the CNT chemiresistive
sensors for detection of different analytes. Lastly, we put forward the remaining
challenges for CNT chemiresistive sensors and outlook the possible opportunity
for CNT chemiresistive sensors in the future.
PMID- 28420196
TI - Probe Sensor Using Nanostructured Multi-Walled Carbon Nanotube Yarn for Selective
and Sensitive Detection of Dopamine.
AB - The demands for electrochemical sensor materials with high strength and
durability in physiological conditions continue to grow and novel approaches are
being enabled by the advent of new electromaterials and novel fabrication
technologies. Herein, we demonstrate a probe-style electrochemical sensor using
highly flexible and conductive multi-walled carbon nanotubes (MWNT) yarns. The
MWNT yarn-based sensors can be fabricated onto micro Pt-wire with a controlled
diameter varying from 100 to 300 um, and then further modified with Nafion via a
dip-coating approach. The fabricated micro-sized sensors were characterized by
electron microscopy, Raman, FTIR, electrical, and electrochemical measurements.
For the first time, the MWNT/Nafion yarn-based probe sensors have been assembled
and assessed for high-performance dopamine sensing, showing a significant
improvement in both sensitivity and selectivity in dopamine detection in presence
of ascorbic acid and uric acid. It offers the potential to be further developed
as implantable probe sensors.
PMID- 28420197
TI - A Novel Auto-Sorting System for Chinese Cabbage Seeds.
AB - This paper presents a novel machine vision-based auto-sorting system for Chinese
cabbage seeds. The system comprises an inlet-outlet mechanism, machine vision
hardware and software, and control system for sorting seed quality. The proposed
method can estimate the shape, color, and textural features of seeds that are
provided as input neurons of neural networks in order to classify seeds as "good"
and "not good" (NG). The results show the accuracies of classification to be
91.53% and 88.95% for good and NG seeds, respectively. The experimental results
indicate that Chinese cabbage seeds can be sorted efficiently using the developed
system.
PMID- 28420198
TI - Chemical Constituents of Supercritical Extracts from Alpinia officinarum and the
Feeding Deterrent Activity against Tribolium castaneum.
AB - Alpinia officinarum has been confirmed to possess bioactivities against some
pests. In this work, a sample was obtained from A. officinarum rhizomes by
supercritical fluid CO2 extraction (SFE). According to GC-MS analysis, the main
chemical components for SFE-sample included benzylacetone (26.77%), 1,7-diphenyl
5-hydroxy-3-heptanone (17.78%), guaiacylacetone (10.03%) and benzenepropanal
(7.42%). The essential oil of A. officinarum rhizomes (LD50 = 20.71 MUg/adult)
exhibited more contact toxicity than SFE extract (LD50 = 82.72 MUg/adult) against
Tribolium castaneum. From SFE extracts, one new compound, 1-phenyl-4-(16,17
dimethyl-9,13-octadiene)-5-isopentenyl-7-(4"-methoxyl-3"-hydroxyl-phenyl)-3
heptanone (3), together with five known compounds identified as 5-hydroxy-1,7
diphenyl-3-heptanone (1), 1,7-diphenyl-4-hepten-3-one (2), galangin (4), galangin
3-methyl ether (5) and pinocembrin (6), were isolated and their feeding deterrent
activities against T. castaneum adults were assessed. It was found that compounds
1-6 had feeding deterrent activities against T. castaneum with feeding deterrent
indices of 18.21%, 18.94%, 19.79%, 26.99%, 20.34%, and 35.81%, respectively, at
the concentration of 1500 ppm. Hence, the essential oil and SFE
extracts/compounds of A. officinarum rhizomes represent promising alternatives in
the control of T. castaneum adults.
PMID- 28420199
TI - Detecting Single-Nucleotides by Tunneling Current Measurements at Sub-MHz
Temporal Resolution.
AB - Label-free detection of single-nucleotides was performed by fast tunneling
current measurements in a polar solvent at 1 MHz sampling rate using SiO2
protected Au nanoprobes. Short current spikes were observed, suggestive of
trapping/detrapping of individual nucleotides between the nanoelectrodes. The
fall and rise features of the electrical signatures indicated signal retardation
by capacitance effects with a time constant of about 10 microseconds. The high
temporal resolution revealed current fluctuations, reflecting the molecular
conformation degrees of freedom in the electrode gap. The method presented in
this work may enable direct characterizations of dynamic changes in single
molecule conformations in an electrode gap in liquid.
PMID- 28420201
TI - A Transcriptomic Comparison of Two Bambara Groundnut Landraces under Dehydration
Stress.
AB - The ability to grow crops under low-water conditions is a significant advantage
in relation to global food security. Bambara groundnut is an underutilised crop
grown by subsistence farmers in Africa and is known to survive in regions of
water deficit. This study focuses on the analysis of the transcriptomic changes
in two bambara groundnut landraces in response to dehydration stress. A cross
species hybridisation approach based on the Soybean Affymetrix GeneChip array has
been employed. The differential gene expression analysis of a water-limited
treatment, however, showed that the two landraces responded with almost
completely different sets of genes. Hence, both landraces with very similar
genotypes (as assessed by the hybridisation of genomic DNA onto the Soybean
Affymetrix GeneChip) showed contrasting transcriptional behaviour in response to
dehydration stress. In addition, both genotypes showed a high expression of
dehydration-associated genes, even under water-sufficient conditions. Several
gene regulators were identified as potentially important. Some are already known,
such as WRKY40, but others may also be considered, namely PRR7, ATAUX2-11,
CONSTANS-like 1, MYB60, AGL-83, and a Zinc-finger protein. These data provide a
basis for drought trait research in the bambara groundnut, which will facilitate
functional genomics studies. An analysis of this dataset has identified that both
genotypes appear to be in a dehydration-ready state, even in the absence of
dehydration stress, and may have adapted in different ways to achieve drought
resistance. This will help in understanding the mechanisms underlying the ability
of crops to produce viable yields under drought conditions. In addition, cross
species hybridisation to the soybean microarray has been shown to be informative
for investigating the bambara groundnut transcriptome.
PMID- 28420200
TI - Integrating Spatial Working Memory and Remote Memory: Interactions between the
Medial Prefrontal Cortex and Hippocampus.
AB - In recent years, two separate research streams have focused on information
sharing between the medial prefrontal cortex (mPFC) and hippocampus (HC).
Research into spatial working memory has shown that successful execution of many
types of behaviors requires synchronous activity in the theta range between the
mPFC and HC, whereas studies of memory consolidation have shown that shifts in
area dependency may be temporally modulated. While the nature of information that
is being communicated is still unclear, spatial working memory and remote memory
recall is reliant on interactions between these two areas. This review will
present recent evidence that shows that these two processes are not as separate
as they first appeared. We will also present a novel conceptualization of the
nature of the medial prefrontal representation and how this might help explain
this area's role in spatial working memory and remote memory recall.
PMID- 28420202
TI - Cereal Consumption among Subjects with Celiac Disease: A Snapshot for Nutritional
Considerations.
AB - BACKGROUND: To our knowledge no study has focused on the pattern of cereal-based
products (CBP) consumption among people with celiac disease (CD). Our study aimed
at evaluating the dietary intake of CBP among patients with CD and comparing it
with a control population. METHODS: Eighty-two volunteers with CD and 77 non-CD
volunteers enrolled throughout Italy were asked to register their consumption of
CBP on specific diaries for three days. RESULTS: CD patients' median three-day
intake of biscuits and crackers was higher compared to controls (65.8 g vs. 22.7
g and 44.7 g vs. 10.6 g, p < 0.05 respectively, Mann-Whitney test). A significant
difference was observed also comparing the two groups for median three-day bread
consumption, with the CD group consuming less bread than controls (109.5 g vs.
150.7 g, p < 0.05, Mann-Whitney test). When assessing regional and gender-related
CBP consumption patterns, significantly higher rice consumption was found among
CD women from Northern Italy compared to CD women from Central and Southern Italy
(p = 0.006 and p = 0.002 respectively, Fisher's exact test). No other significant
differences were observed. CONCLUSIONS: Our results provide a snapshot of the
overall consumption of CBP among Italian subjects with CD. Altogether, these data
show that, despite minor differences, dietary consumption of CBP among CD
patients is similar to the general population.
PMID- 28420203
TI - Comments to Article by Solah VA et al., Nutrients 2017, 9, 149.
AB - n/a.
PMID- 28420205
TI - Do Chinese Children Get Enough Micronutrients?
AB - The aim of this study was to examine usual daily micronutrient intake of Chinese
children based on data from the 2011 China Health and Nutrition Survey. We
analyzed data from 4 to 17-year-old participants, who provided dietary data on
three consecutive days combined with the household weighing method in 2011. Usual
daily intake of each nutrient was estimated using a mixed effects model based on
the China Food Composition published in 2009. The means, medians and percentages
below Estimated Average Requirements (EAR) were reported for selected
micronutrients, including calcium, sodium, potassium, iron, zinc, selenium,
vitamin A, thiamine, riboflavin and vitamin C. For sodium and potassium, the
means and the distribution of intakes were compared to the Adequate Intake (AI)
level. The average usual daily intakes of all micronutrients increase with age,
and the intakes of boys were found to be higher than girls in the same age group.
The average calcium intake increased from 272 mg/day in 4-6 years to 391 mg/day
in 14-17 years, but the percentage of inadequate calcium intake remained very
high (>96%). The prevalence of inadequacy of calcium was the highest among the
mineral nutrients reported in this study. As the requirements of micronutrients
increased with age, the percentage of subjects with inadequate intake increased
in the 11-17 years age groups. Among 14-17 years group, the percentages of study
participants with dietary intakes of calcium, iron, zinc, selenium, vitamin A,
thiamine, riboflavin and vitamin C below the EAR were 96.8%, 18.8%, 37.6%, 72.8%,
36.8%, 91.8%. 85.9% and 75.5%, respectively. Among 11-13 years group, the
percentages of study participants with dietary intakes of iron, zinc and vitamin
A below the EAR were 23.5%, 41.5%, and 41.6%, respectively. Thus, micronutrient
deficiency is a problem in Chinese children. Nutrition education and intervention
programs are needed to address these nutritional gaps.
PMID- 28420204
TI - Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical
Review.
AB - There is a direct relationship between fructose intake and serum levels of uric
acid (UA), which is the final product of purine metabolism. Recent preclinical
and clinical evidence suggests that chronic hyperuricemia is an independent risk
factor for hypertension, metabolic syndrome, and cardiovascular disease. It is
probably also an independent risk factor for chronic kidney disease, Type 2
diabetes, and cognitive decline. These relationships have been observed for high
serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to
high serum UA levels (5-6 mg/dL). In this regard, blood UA levels are much higher
in industrialized countries than in the rest of the world. Xanthine-oxidase
inhibitors can reduce UA and seem to minimize its negative effects on vascular
health. Other dietary and pathophysiological factors are also related to UA
production. However, the role of fructose-derived UA in the pathogenesis of
cardiometabolic disorders has not yet been fully clarified. Here, we critically
review recent research on the biochemistry of UA production, the relationship
between fructose intake and UA production, and how this relationship is linked to
cardiometabolic disorders.
PMID- 28420206
TI - The Status of Biofilms in Penile Implants.
AB - Erectile dysfunction is prevalent among men and will continue to become more so
with the aging population. Of the available treatment options, implantable
prosthetic devices are typically thought of as a third line treatment even though
they have the highest satisfaction rate and continually improving success rates.
Infection and mechanical failure are the most common reasons for implant revision
in the past. Since the development of more reliable devices, bacterial biofilms
are coming to the forefront of discussion as causes of required revision.
Biofilms are problematic as they are ubiquitous and exceedingly difficult to
prevent or treat.
PMID- 28420207
TI - TbetaRII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2
In Vitro.
AB - The transforming growth factor-beta (TGFbeta) family signaling pathways play an
important role in regulatory cellular networks and exert specific effects on
developmental programs during embryo development. However, the function of
TGFbeta signaling pathways on the early kidney development remains unclear. In
this work, we aim to detect the underlying role of TGFbeta type II receptor
(TbetaRII) in vitro, which has a similar expression pattern as the crucial
regulator Six2 during early kidney development. Firstly, the 5-ethynyl-2'
deoxyuridine (EdU) assay showed knock down of TbetaRII significantly decreased
the proliferation ratio of metanephric mesenchyme (MM) cells. Additionally, real
time Polymerase Chain Reaction (PCR) and Western blot together with
immunofluorescence determined that the mRNA and protein levels of Six2 declined
after TbetaRII knock down. Also, Six2 was observed to be able to partially rescue
the proliferation phenotype caused by the depletion of TbetaRII. Moreover,
bioinformatics analysis and luciferase assay indicated Smad3 could
transcriptionally target Six2. Further, the EdU assay showed that Smad3 could
also rescue the inhibition of proliferation caused by the knock down of TbetaRII.
Taken together, these findings delineate the important function of the TGFbeta
signaling pathway in the early development of kidney and TbetaRII was shown to be
able to promote the expression of Six2 through Smad3 mediating transcriptional
regulation and in turn activate the proliferation of MM cells.
PMID- 28420208
TI - Serum Insulin-Like Growth Factor Axis and the Risk of Pancreatic Cancer:
Systematic Review and Meta-Analysis.
AB - OBJECTIVE: To investigate the association between serum concentration of insulin
like growth factor (IGF) and the risk of pancreatic cancer (PaC). METHODS: We
identified eligible studies in Medline and EMBASE databases (no reference trials
from 2014 to 2016) in addition to the reference lists of original studies and
review articles on this topic. A summary of relative risks with 95% confidence
intervals (CI) was calculated using a random-effects model. The heterogeneity
between studies was assessed using Cochran Q and I2 statistics. RESULTS: Ten
studies (seven nested case-control studies and three retrospective case-control
studies) were selected as they met our inclusion criteria in this meta-analysis.
All these studies were published between 1997 and 2013. The current data
suggested that serum concentrations of IGF-I, IGF-II and insulin-like growth
factor binding protein-3 (IGFBP-3)in addition to the IGF-I/IGFBP-3 ratio were not
associated with an increased risk of PaC (Summary relative risks (SRRs) = 0.92,
95% CI: 0.67-1.16 for IGF-I; SRRs = 0.84, 95% CI: 0.54-1.15 for IGF-II; SRRs =
0.93, 95% CI: 0.69-1.17 for IGFBP-3; SRRs = 0.97, 95% CI: 0.71-1.23 for IGF
I/IGFBP-3 ratio). There was no publication bias in the present meta-analysis.
CONCLUSION: Serum concentrations of IGF-I, IGF-II, IGFBP-1 and IGFBP-3 as well as
the IGF-I/IGFBP-3 ratio were not associated with increased risk of PaC.
PMID- 28420209
TI - Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase
in Pregnant Women.
AB - Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD)
activity are considered biomarkers of lead exposure and lead toxicity,
respectively. The present study was designed to investigate the association
between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of
633 pregnant women aged 13-43 years participated in this study. Blood lead was
measured by a graphite furnace atomic absorption spectrometer. ALAD activity was
measured spectrophotometrically. Mean blood lead was 2.09 +/- 2.34 ug/dL; and 26
women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5
ug/dL. ALAD activity was significantly lower in women with levels of lead >=5
ug/dL compared to those with BLLs < 5 ug/dL (p = 0.002). To reduce the influence
of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A
significant negative correlation between blood lead and ALAD activity was
observed in the fourth quartile of BLLs (r = -0.113; p < 0.01). Among women with
blood lead concentrations >=2.2 ug/dL ALAD activity was negatively correlated
with BLLs (r = -0.413; p < 0.01). Multiple linear regression demonstrated that
inhibition of ALAD in pregnant women may occur at levels of lead in blood above
2.2 ug/dL.
PMID- 28420210
TI - Predictors of Active Extravasation and Complications after Conventional
Angiography for Acute Intraabdominal Bleeding.
AB - Conventional angiography is used to evaluate and treat possible sources of
intraabdominal bleeding, though it may cause complications such as contrast
induced nephropathy (CIN). The study's purpose was to identify factors predicting
active extravasation and complications during angiography for acute
intraabdominal bleeding. All conventional angiograms for acute bleeding (January
2013-June 2015) were reviewed retrospectively, including 75 angiograms for
intraabdominal bleeding in 70 patients. Demographics, comorbidities, vital signs,
complications within one month, and change in hematocrit (DeltaHct) and fluids
and blood products administered over the 24 h prior to angiography were recorded.
Of 75 exams, 20 (27%) demonstrated extravasation. DeltaHct was the only
independent predictor of extravasation (p = 0.017), with larger DeltaHct (-17%)
in patients with versus those without extravasation (-1%) (p = 0.01). CIN was the
most common complication, occurring in 10 of 66 angiograms (15%). Glomerular
filtration rate (GFR) was the only independent predictor (p = 0.03); 67% of
patients with GFR < 30, 29% of patients with GFR 30-60, and 8% of patients with
GFR > 60 developed CIN. For patients with intraabdominal bleeding, greater
DeltaHct decrease over 24 h before angiography predicts active extravasation. Pre
existing renal impairment predicts CIN. Patients with large hematocrit declines
should be triaged for rapid angiography, though benefits can be weighed with the
risk of renal impairment.
PMID- 28420211
TI - Cognitive Remediation Therapy for Adolescents with Anorexia Nervosa-Treatment
Satisfaction and the Perception of Change.
AB - Cognitive remediation therapy (CRT) has recently been developed for children and
adolescents with anorexia nervosa (AN). It focuses on decreasing rigid cognitions
and behaviors, as well as increasing central coherence. Overall, CRT has been
proven feasible for young individuals with AN, but little is known regarding the
specifics of its feasibility, and the perception of change associated with the
intervention. Consequently, the aim of the current study was to explore service
users' perspective on CRT with a specific focus on treatment delivery, treatment
content, and perceived change. Twenty adolescents (age 13-18) with AN
participated in a 10-session course of CRT. A 20-item treatment evaluation
questionnaire was administered at the end of treatment, focusing on four aspects
of the intervention: (1) general attitudes towards treatment, (2) treatment
specifics, (3) the perception of change and (4) the patient-therapist relation.
The main findings suggest high levels of treatment satisfaction, but somewhat
limited perceptions of change. The current study is one of the most detailed
accounts of adolescents' perspective on CRT published on eating disorders, and
highlights several important aspects of the treatment viewed through the eye of
the receiver.
PMID- 28420212
TI - Nutritional Status Predicts 10-Year Mortality in Patients with End-Stage Renal
Disease on Hemodialysis.
AB - Protein-energy wasting (PEW) is associated with mortality in patients with end
stage renal disease (ESRD) on maintenance hemodialysis. The correct diagnosis of
PEW is extremely important in order to predict clinical outcomes. However, it is
unclear which parameters should be used to diagnose PEW. Therefore, this
retrospective observational study investigated the relationship between mortality
and nutritional parameters in ESRD patients on maintenance hemodialysis. A total
of 144 patients were enrolled. Nutritional parameters, including body mass index,
serum albumin, dietary intake, normalized protein catabolic rate (nPCR), and
malnutrition inflammation score (MIS), were measured at baseline. Fifty-three
patients died during the study. Survivors had significantly higher nPCR (1.10 +/-
0.24 g/kg/day vs. 1.01 +/- 0.21 g/kg/day; p = 0.048), energy intake (26.7 +/- 5.8
kcal/kg vs. 24.3 +/- 4.2 kcal/kg; p = 0.009) and protein intake (0.91 +/- 0.21
g/kg vs. 0.82 +/- 0.24 g/kg; p = 0.020), and lower MIS (5.2 +/- 2.3 vs. 6.1 +/-
2.1, p = 0.039). In multivariable analysis, energy intake <25 kcal/kg (HR 1.860,
95% CI 1.018-3.399; p = 0.044) and MIS > 5 (HR 2.146, 95% CI 1.173-3.928; p =
0.013) were independent variables associated with all-cause mortality. These
results suggest that higher MIS and lower energy intake are harmful to ESRD
patients on maintenance hemodialysis. Optimal energy intake could reduce
mortality in these patients.
PMID- 28420213
TI - Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for
Targeting Retinoblastoma.
AB - The aim of this study was to develop a novel folate receptor-targeted drug
delivery system for retinoblastoma cells using a promising anticancer agent,
curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used
as a targeting moiety to enhance the targeting and bioavailability of CDF. For
this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA
FA) was synthesized and utilized to improve the aqueous solubility of a highly
hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery
to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and
characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition
(HPLC) for estimating CDF was determined and validated. The formulation was
optimized to achieve maximum entrapment of CDF. The particle size of the micelles
was measured and confirmed by dynamic light scattering (DLS) and transmission
electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI
RB) retinoblastoma cells. Results showed that the solubility of CDF could be
increased with the newly-synthesized polymer, and the entrapment efficiency was
>85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a
narrow size distribution. The formulation did not show any adverse cytotoxicity
on a human retinal pigment epithelial cell (ARPE-19), indicating its safety.
However, it showed significant cell killing activity in both Y-79 and WERI-RB
retinoblastoma cell lines, indicating its potency in killing cancer cells. In
conclusion, the folic acid-conjugated SMA loaded with CDF showed promising
potential with high safety and pronounced anticancer activity on the tested
retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could
be a viable option as an alternative approach to current retinoblastoma
therapies.
PMID- 28420214
TI - Multi-Mode Estimation for Small Fixed Wing Unmanned Aerial Vehicle Localization
Based on a Linear Matrix Inequality Approach.
AB - Information fusion from multiple sensors ensures the accuracy and robustness of a
navigation system, especially in the absence of global positioning system (GPS)
data which gets degraded in many cases. A way to deal with multi-mode estimation
for a small fixed wing unmanned aerial vehicle (UAV) localization framework is
proposed, which depends on utilizing a Luenberger observer-based linear matrix
inequality (LMI) approach. The proposed estimation technique relies on the
interaction between multiple measurement modes and a continuous observer. The
state estimation is performed in a switching environment between multiple active
sensors to exploit the available information as much as possible, especially in
GPS-denied environments. Luenberger observer-based projection is implemented as a
continuous observer to optimize the estimation performance. The observer gain
might be chosen by solving a Lyapunov equation by means of a LMI algorithm.
Convergence is achieved by utilizing the linear matrix inequality (LMI), based on
Lyapunov stability which keeps the dynamic estimation error bounded by selecting
the observer gain matrix (L). Simulation results are presented for a small UAV
fixed wing localization problem. The results obtained using the proposed approach
are compared with a single mode Extended Kalman Filter (EKF). Simulation results
are presented to demonstrate the viability of the proposed strategy.
PMID- 28420215
TI - A Phonocardiographic-Based Fiber-Optic Sensor and Adaptive Filtering System for
Noninvasive Continuous Fetal Heart Rate Monitoring.
AB - This paper focuses on the design, realization, and verification of a novel
phonocardiographic- based fiber-optic sensor and adaptive signal processing
system for noninvasive continuous fetal heart rate (fHR) monitoring. Our proposed
system utilizes two Mach-Zehnder interferometeric sensors. Based on the analysis
of real measurement data, we developed a simplified dynamic model for the
generation and distribution of heart sounds throughout the human body. Building
on this signal model, we then designed, implemented, and verified our adaptive
signal processing system by implementing two stochastic gradient-based
algorithms: the Least Mean Square Algorithm (LMS), and the Normalized Least Mean
Square (NLMS) Algorithm. With this system we were able to extract the fHR
information from high quality fetal phonocardiograms (fPCGs), filtered from
abdominal maternal phonocardiograms (mPCGs) by performing fPCG signal peak
detection. Common signal processing methods such as linear filtering, signal
subtraction, and others could not be used for this purpose as fPCG and mPCG
signals share overlapping frequency spectra. The performance of the adaptive
system was evaluated by using both qualitative (gynecological studies) and
quantitative measures such as: Signal-to-Noise Ratio-SNR, Root Mean Square Error
RMSE, Sensitivity-S+, and Positive Predictive Value-PPV.
PMID- 28420216
TI - Fast Bragg Grating Inscription in PMMA Polymer Optical Fibres: Impact of Thermal
Pre-Treatment of Preforms.
AB - In this work, fibre Bragg gratings (FBGs) were inscribed in two different undoped
poly- (methyl methacrylate) (PMMA) polymer optical fibres (POFs) using different
types of UV lasers and their inscription times, temperature and strain
sensitivities are investigated. The POF Bragg gratings (POFBGs) were inscribed
using two UV lasers: a continuous UV HeCd @325 nm laser and a pulsed UV KrF @248
nm laser. Two PMMA POFs are used in which the primary and secondary preforms
(during the two-step drawing process) have a different thermal treatment. The
PMMA POFs drawn in which the primary or secondary preform is not specifically pre
treated need longer inscription time than the fibres drawn where both preforms
have been pre-annealed at 80 degrees C for 2 weeks. Using both UV lasers, for
the latter fibre much less inscription time is needed compared to another
homemade POF. The properties of a POF fabricated with both preforms thermally
well annealed are different from those in which just one preform step process is
thermally treated, with the first POFs being much less sensitive to thermal
treatment. The influence of annealing on the strain and temperature sensitivities
of the fibres prior to FBG inscription is also discussed, where it is observed
that the fibre produced from a two-step drawing process with well-defined pre
annealing of both preforms did not produce any significant difference in
sensitivity. The results indicate the impact of preform thermal pre-treatment
before the PMMA POFs drawing, which can be an essential characteristic in the
view of developing POF sensors technology.
PMID- 28420217
TI - Microfluidic EBG Sensor Based on Phase-Shift Method Realized Using 3D Printing
Technology.
AB - In this article, we propose a novel microfluidic microstrip electromagnetic band
gap (EBG) sensor realized using cost-effective 3D printing technology. Microstrip
sensor allows monitoring of the fluid properties flowing in the microchannel
embedded between the microstrip line and ground plane. The sensor's operating
principle is based on the phase-shift method, which allows the characterization
at a single operating frequency of 6 GHz. The defected electromagnetic band gap
(EBG) structure is realized as a pattern in the microstrip ground plane to
improve sensor sensitivity. The designed microfluidic channel is fabricated using
a fused deposition modelling (FDM) 3D printing process without additional
supporting layers, while the conductive layers are realized using sticky
aluminium tape. The measurement results show that the change of permittivity of
the fluid in the microfluidic channel from 1 to 80 results in the phase-shift
difference of almost 90 degrees . The potential application is demonstrated
through the implementation of a proposed sensor for the detection of toluene
concentration in toluene-methanol mixture where various concentrations of toluene
were analysed.
PMID- 28420218
TI - A Latency and Coverage Optimized Data Collection Scheme for Smart Cities Based on
Vehicular Ad-hoc Networks.
AB - Using mobile vehicles as "data mules" to collect data generated by a huge number
of sensing devices that are widely spread across smart city is considered to be
an economical and effective way of obtaining data about smart cities. However,
currently most research focuses on the feasibility of the proposed methods
instead of their final performance. In this paper, a latency and coverage
optimized data collection (LCODC) scheme is proposed to collect data on smart
cities through opportunistic routing. Compared with other schemes, the efficiency
of data collection is improved since the data flow in LCODC scheme consists of
not only vehicle to device transmission (V2D), but also vehicle to vehicle
transmission (V2V). Besides, through data mining on patterns hidden in the smart
city, waste and redundancy in the utilization of public resources are mitigated,
leading to the easy implementation of our scheme. In detail, no extra supporting
device is needed in the LCODC scheme to facilitate data transmission. A large
scale and real-world dataset on Beijing is used to evaluate the LCODC scheme.
Results indicate that with very limited costs, the LCODC scheme enables the
average latency to decrease from several hours to around 12 min with respect to
schemes where V2V transmission is disabled while the coverage rate is able to
reach over 30%.
PMID- 28420219
TI - Integrated Flexible Electronic Devices Based on Passive Alignment for
Physiological Measurement.
AB - This study proposes a simple method of fabricating flexible electronic devices
using a metal template for passive alignment between chip components and an
interconnect layer, which enabled efficient alignment with high accuracy. An
electrocardiogram (ECG) sensor was fabricated using 20 um thick polyimide (PI)
film as a flexible substrate to demonstrate the feasibility of the proposed
method. The interconnect layer was fabricated by a two-step photolithography
process and evaporation. After applying solder paste, the metal template was
placed on top of the interconnect layer. The metal template had rectangular holes
at the same position as the chip components on the interconnect layer.
Rectangular hole sizes were designed to account for alignment tolerance of the
chips. Passive alignment was performed by simply inserting the components in the
holes of the template, which resulted in accurate alignment with positional
tolerance of less than 10 um based on the structural design, suggesting that our
method can efficiently perform chip mounting with precision. Furthermore, a
fabricated flexible ECG sensor was easily attachable to the curved skin surface
and able to measure ECG signals from a human subject. These results suggest that
the proposed method can be used to fabricate epidermal sensors, which are mounted
on the skin to measure various physiological signals.
PMID- 28420220
TI - The Maximal C3 Self-Complementary Trinucleotide Circular Code X in Genes of
Bacteria, Archaea, Eukaryotes, Plasmids and Viruses.
AB - In 1996, a set X of 20 trinucleotides was identified in genes of both prokaryotes
and eukaryotes which has on average the highest occurrence in reading frame
compared to its two shifted frames. Furthermore, this set X has an interesting
mathematical property as X is a maximal C 3 self-complementary trinucleotide
circular code. In 2015, by quantifying the inspection approach used in 1996, the
circular code X was confirmed in the genes of bacteria and eukaryotes and was
also identified in the genes of plasmids and viruses. The method was based on the
preferential occurrence of trinucleotides among the three frames at the gene
population level. We extend here this definition at the gene level. This new
statistical approach considers all the genes, i.e., of large and small lengths,
with the same weight for searching the circular code X . As a consequence, the
concept of circular code, in particular the reading frame retrieval, is directly
associated to each gene. At the gene level, the circular code X is strengthened
in the genes of bacteria, eukaryotes, plasmids, and viruses, and is now also
identified in the genes of archaea. The genes of mitochondria and chloroplasts
contain a subset of the circular code X . Finally, by studying viral genes, the
circular code X was found in DNA genomes, RNA genomes, double-stranded genomes,
and single-stranded genomes.
PMID- 28420221
TI - A Narrative Review: Actigraphy as an Objective Assessment of Perioperative Sleep
and Activity in Pediatric Patients.
AB - Sleep is an important component of pediatric health and is crucial for cognitive
development. Actigraphy is a validated, objective tool to capture sleep and
movement data that is increasingly being used in the perioperative context. The
aim of this review is to present recent pediatric studies that utilized
actigraphy in the perioperative period, highlight gaps in the literature, and
provide recommendations for future research. A literature search was completed
using OVID and PubMed databases and articles were selected for inclusion based on
relevance to the topic. The literature search resulted in 13 papers that utilized
actigraphic measures. Results of the review demonstrated that actigraphy has been
used to identify predictors and risk factors for poor postoperative sleep,
examine associations among perioperative pain and sleep patterns, and assess
activity and energy expenditure in both inpatient and outpatient settings. We
propose expansion of actigraphy research to include assessment of sleep via
actigraphy to: predict functional recovery in pediatric populations, to study
postoperative sleep in high-risk pediatric patients, to test the efficacy of
perioperative interventions, and to assess outcomes in special populations for
which self-report data on sleep and activity is difficult to obtain.
PMID- 28420222
TI - How Sensors Might Help Define the External Exposome.
AB - The advent of the exposome concept, the advancement of mobile technology,
sensors, and the "internet of things" bring exciting opportunities to exposure
science. Smartphone apps, wireless devices, the downsizing of monitoring
technologies, along with lower costs for such equipment makes it possible for
various aspects of exposure to be measured more easily and frequently. We discuss
possibilities and lay out several criteria for using smart technologies for
external exposome studies. Smart technologies are evolving quickly, and while
they provide great promise for advancing exposure science, many are still in
developmental stages and their use in epidemiology and risk studies must be
carefully considered. The most useable technologies for exposure studies at this
time relate to gathering exposure-factor data, such as location and activities.
Development of some environmental sensors (e.g., for some air pollutants, noise,
UV) is moving towards making the use of these more reliable and accessible to
research studies. The possibility of accessing such an unprecedented amount of
personal data also comes with various limitations and challenges, which are
discussed. The advantage of improving the collection of long term exposure factor
data is that this can be combined with more "traditional" measurement data to
model exposures to numerous environmental factors.
PMID- 28420223
TI - Clinical and Molecular Characterization of Patients with Fructose 1,6
Bisphosphatase Deficiency.
AB - Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare, autosomal recessive
inherited disease caused by the mutation of the FBP1 gene, the incidence is
estimated to be between 1/350,000 and 1/900,000. The symptoms of affected
individuals are non-specific and are easily confused with other metabolic
disorders. The present study describes the clinical features of four Chinese
pediatric patients who presented with hypoglycemia, hyperlactacidemia, metabolic
acidosis, and hyperuricemia. Targeted-next generation sequencing using the
Agilent SureSelect XT Inherited Disease Panel was used to screen for causal
variants in the genome, and the clinically-relevant variants were subsequently
verified using Sanger sequencing. Here, DNA sequencing identified six variations
of the FBP1 gene (NM_000507.3) in the four patients. In Case 1, we found a
compound heterozygous mutations of c.704delC (p.Pro235GlnfsX42) (novel) and
c.960_961insG (p.Ser321Valfs) (known pathogenic). In Case 2, we found a compound
heterozygous mutations of c.825 + 1G>A and c.960_961insG (both were known
pathogenically). In Case 3, a homozygous missense mutation of c.355G>A
(p.Asp119Asn) (reported in ClinVar database without functional study) was found.
Case 4 had a compound heterozygous mutations c.720_729del (p.Tyr241GlyfsX33)
(novel) and c.490G>A (p.Gly164Ser) (known pathogenically). Further in vitro
studies in the COS-7cell line demonstrated that the mutation of ASP119ASN had no
impact on protein expression, but decreased the enzyme activity, and with which
the clinical significance of Asp119Asn can be determined to be likely pathogenic.
This report not only expands upon the known spectrum of variation of the FBP1
gene, but also deepens our understanding of the clinical features of FBPase
deficiency.
PMID- 28420224
TI - Silk Fibroin-Alginate-Hydroxyapatite Composite Particles in Bone Tissue
Engineering Applications In Vivo.
AB - The aim of this study was to evaluate the in vivo bone regeneration capability of
alginate (AL), AL/hydroxyapatite (HA), and AL/HA/silk fibroin (SF) composites.
Forty Sprague Dawley rats were used for the animal experiments. Central calvarial
bone (diameter: 8.0 mm) defects were grafted with AL, AL/HA, or AL/HA/SF. New
bone formation was evaluated by histomorphometric analysis. To demonstrate the
immunocompatibility of each group, the level of tumor necrosis factor (TNF)-alpha
expression was studied by immunohistochemistry (IHC) and quantitative reverse
transcription polymerase chain reaction (qRT-PCR) at eight weeks post
implantation. Additionally, osteogenic markers, such as fibroblast growth factor
(FGF)-23, osteoprotegerin (OPG), and Runt-related transcription factor (Runx2)
were evaluated by qPCR or IHC at eight weeks post implantation. The AL/HA/SF
group showed significantly higher new bone formation than did the control group
(p = 0.044) and the AL group (p = 0.035) at four weeks post implantation.
Additionally, the AL/HA/SF group showed lower relative TNF-alpha mRNA levels and
higher FGF-23 mRNA levels than the other groups did at eight weeks post
implantation. IHC results demonstrated that the AL/HA/SF group had lower TNF
alpha expression and higher OPG and Runx2 expression at eight weeks post
implantation. Additionally, no evidence of the inflammatory reaction or giant
cell formation was observed around the residual graft material. We concluded that
the AL/HA/SF composite could be effective as a scaffold for bone tissue
engineering.
PMID- 28420226
TI - Determination of Magnetic Parameters of Maghemite (gamma-Fe2O3) Core-Shell
Nanoparticles from Nonlinear Magnetic Susceptibility Measurements.
AB - Method of determining of magnetic moment and size from measurements of dependence
of the nonlinear magnetic susceptibility upon magnetic field is proposed,
substantiated and tested for superparamagnetic nanoparticles (SPNP) of the
"magnetic core-polymer shell" type which are widely used in biomedical
technologies. The model of the induction response of the SPNP ensemble on the
combined action of the magnetic harmonic excitation field and permanent bias
field is built, and the analysis of possible ways to determine the magnetic
moment and size of the nanoparticles as well as the parameters of the
distribution of these variables is performed. Experimental verification of the
proposed method was implemented on samples of SPNP with maghemite core in dry
form as well as in colloidal systems. The results have been compared with the
data obtained by other methods. Advantages of the proposed method are analyzed
and discussed, particularly in terms of its suitability for routine express
testing of SPNP for biomedical technology.
PMID- 28420225
TI - Engineering the Complex-Valued Constitutive Parameters of Metamaterials for
Perfect Absorption.
AB - We theoretically studied how to directly engineer the constitutive parameters of
metamaterials for perfect absorbers of electromagnetic waves. As an example, we
numerically investigated the necessary refractive index n and extinction
coefficient k and the relative permittivity epsilon and permeability MU of a
metamaterial anti-reflection layer, which could cancel the reflection from a
hydrogenated amorphous silicon (alpha-Si:H) thin film on a metal substrate,
within the visible wavelength range from 300 to 800 nm. We found that the
metamaterial anti-reflection layer should have a negative refractive index (n <
0) for short-wavelength visible light but have a positive refractive index (n >
0) for long-wavelength visible light. The relative permittivity epsilon and
permeability MU could be fitted by the Lorentz model, which exhibited electric
and magnetic resonances, respectively.
PMID- 28420227
TI - Efficacy and tolerability of a plant-based, multi-component cream (Ginetrox(r))
in vulvovaginal disorders of the genitourinary syndrome during menopause.
AB - BACKGROUND: Genitourinary syndrome of menopause (GSM) is a symptomatic condition
including vaginal dryness, irritation, dyspareunia and recurrent urinary tract
infections which affects 40-54% of post-menopausal women. Although several
estrogen-based therapies are available, it is generally preferable to avoid
hormonal therapy, particularly in women with mild symptoms or at risk for
estrogen-responsive neoplasia. Therefore, the most common treatment options are
over-the-counter vaginal creams for symptomatic relief. METHODS: Thirty-three
postmenopausal women suffering from GSM were enrolled in this observational
study. A multi-component cream (Ginetrox(r), Indena, Milan, Italy) was applied on
the vestibular area of the vagina for three months. The primary endpoints were:
vaginal burning and/or pain, assessed by Visual Analog Scale and dyspareunia,
assessed using the Marinoff Score. As a secondary endpoint, vestibular health was
evaluated through a four-point scale. Side effects and adherence to treatment
were also recorded. RESULTS: Statistically significant improvement was observed
in pain scores and dyspareunia at the end of the treatment compared to baseline
values. The vestibular health index significantly decreased after 3 months.
Tolerability was acceptable. CONCLUSIONS: This preliminary study suggests that
the plant-based, multi-component cream Ginetrox(r) could be effective and safe in
counteracting menopause-related vaginal discomfort symptoms.
PMID- 28420228
TI - Influence of Order within Nonpolar Monolayers on Hydrophobic Interactions.
AB - We report an experimental investigation of the influence of molecular-level order
(crystallinity) within nonpolar monolayers on hydrophobic interactions. The
measurements were performed using gold film-supported monolayers formed from
alkanethiols (CH3(CH2)nSH, with n ranging from 3 to 17), which we confirmed by
using polarization-modulation infrared reflection-adsorption spectroscopy to
exhibit chain-length-dependent order (methylene peak moves from 2926 to 2919 cm
1, corresponding to a transition from liquid- to quasi-crystalline-like order) in
the absence of substantial changes in chain density (constant methyl peak
intensity). By using monolayer-covered surfaces immersed in either aqueous
triethanolamine (TEA, 10 mM, pH 7.0) or pure methanol, we quantified hydrophobic
and van der Waals contributions to adhesive interactions between identical pairs
of surfaces (measured using an atomic force microscope) as a function of the
length and order of the aliphatic chains within the monolayers. In particular, we
measured pull-off forces arising from hydrophobic adhesion to increase in a
nonlinear manner with chain length (abrupt increase between n = 5 and 6 from 2.1
+/- 0.3 to 14.1 +/- 0.7 nN) and to correlate closely with a transition from a
liquid-like to crystalline-like monolayer phase. In contrast, adhesion in
methanol increased gradually with chain length from 0.3 +/- 0.1 to 3.2 +/- 0.3 nN
for n = 3 to 7 and then did not change further with an increase in chain length.
These results lead to the hypothesis that order within nonpolar monolayers
influences hydrophobic interactions. Additional support for this hypothesis was
obtained from measurements reported in this paper using long-chain alkanethiols
(ordered) and alkenethiols (disordered). The results are placed into the context
of recent spectroscopic studies of hydrogen bonding of water at nonpolar
monolayers. Overall, our study provides new insight into factors that influence
hydrophobic interactions at nonpolar monolayers.
PMID- 28420229
TI - High-Affinity Copolymers Inhibit Digestive Enzymes by Surface Recognition.
AB - This account presents a general method for the construction of polymeric surface
binders for digestion enzymes. Two prominent parts, namely, the modification of
the copolymer composition and the screening assay for the most powerful
inhibitors are both amenable to parallelization. The concept hinges on the
appropriate selection of amino-acid-selective comonomers, their free radical
copolymerization, and subsequent screening of the resulting copolymer library for
efficient enzyme inhibition. A microscale synthetic procedure for the
copolymerization process was developed, which produces water-soluble affinity
polymers that can be stored for years at room temperature. Initial parallel
screening was conducted in standard enzyme assays to identify polymeric
inhibitors, which were subsequently subjected to determination of IC50 values for
their target enzyme. For all digestion enzymes, except elastase, a number of
polymer inhibitors were found, some of which were selective toward one or two
protein targets. Since the key monomers of the best inhibitors bind to amino acid
residues in the direct vicinity of the active site, we conclude that efficient
coverage of the immediate environment by the copolymers is critical. Strong
interference with enzymatic activity is brought about by blocking the substrate
access and product exit to and from the active site.
PMID- 28420230
TI - An Unambiguous Nomenclature for the Acyl-quinic Acids Commonly Known as
Chlorogenic Acids.
AB - The history of the acyl-quinic acids is briefly reviewed, the merits and
limitations of the various nomenclature systems applicable are critically
compared, and their limitations are highlighted, in particular their inability to
provide an unambiguous description of all quinic acid enantiomers and
diastereoisomers and associated acyl-quinic acids. Recommendations are made for a
nomenclature system that in combination with IUPAC numbering achieves this
objective. A comprehensive set of structures for the quinic acid enantiomers and
diastereoisomers is presented. The Supporting Information provides an explanation
of trivial names and a decision tree to determine which quinic acid isomer a
structure represents.
PMID- 28420231
TI - Biological Control of Aflatoxin Contamination in U.S. Crops and the Use of
Bioplastic Formulations of Aspergillus flavus Biocontrol Strains To Optimize
Application Strategies.
AB - Aflatoxin contamination has a major economic impact on crop production in the
southern United States. Reduction of aflatoxin contamination in harvested crops
has been achieved by applying nonaflatoxigenic biocontrol Aspergillus flavus
strains that can out-compete wild aflatoxigenic A. flavus, reducing their numbers
at the site of application. Currently, the standard method for applying
biocontrol A. flavus strains to soil is using a nutrient-supplying carrier (e.g.,
pearled barley for Afla-Guard). Granules of Bioplastic (partially acetylated corn
starch) have been investigated as an alternative nutritive carrier for biocontrol
agents. Bioplastic granules have also been used to prepare a sprayable biocontrol
formulation that gives effective reduction of aflatoxin contamination in
harvested corn kernels with application of much smaller amounts to leaves later
in the growing season. The ultimate goal of biocontrol research is to produce
biocontrol systems that can be applied to crops only when long-range weather
forecasting indicates they will be needed.
PMID- 28420232
TI - Gas-Phase Carboxylic Acids in a University Classroom: Abundance, Variability, and
Sources.
AB - Gas-phase carboxylic acids are ubiquitous in ambient air, yet their indoor
occurrence and abundance are poorly characterized. To fill this gap, we measured
gas-phase carboxylic acids in real-time inside and outside of a university
classroom using a high-resolution time-of-flight chemical ionization mass
spectrometer (HRToF-CIMS) equipped with an acetate ion source. A wide variety of
carboxylic acids were identified indoors and outdoors, including monoacids,
diacids, hydroxy acids, carbonyl acids, and aromatic acids. An empirical
parametrization was derived to estimate the sensitivity (ion counts per ppt of
the analytes) of the HRToF-CIMS to the acids. The campaign-average concentration
of carboxylic acids measured outdoors was 1.0 ppb, with the peak concentration
occurring in daytime. The average indoor concentration of carboxylic acids was
6.8 ppb, of which 87% was contributed by formic and lactic acid. While carboxylic
acids measured outdoors displayed a single daytime peak, those measured indoors
displayed a daytime and a nighttime peak. Besides indoor sources such as off
gassing of building materials, evidence for acid production from indoor chemical
reactions with ozone was found. In addition, some carboxylic acids measured
indoors correlated to CO2 in daytime, suggesting that human occupants may
contribute to their abundance either through direct emissions or surface
reactions.
PMID- 28420233
TI - Novel Hydrogen-Bonding Cross-Linking Aggregation-Induced Emission: Water as a
Fluorescent "Ribbon" Detected in a Wide Range.
AB - The development of efficient sensors for detection of the water content in a wide
detection range is highly desirable for balance in many industrial processes and
products. Presented herein are six novel different substituted Schiff base Zn(II)
complexes, which exhibit the remarkable capability to detect traces of water in a
wide linear range (most can reach 0-94%, v/v), low detection limit of 0.2% (v/v),
and rapid response time of 8 s in various organic solvents by virtue of an
unusual water-activated hydrogen-bonding cross-linking AIE (WHCAIE) mechanism. As
a proof-of-concept, the WHCAIE mechanism is explained well by single X-ray
diffraction, absorption spectra, fluorescence spectra, dynamic light scattering,
1H NMR spectra, and theoretical calculations. In addition, the molecules
demonstrated their application for the detection of humidity (42-80%). These
Schiff base Zn(II) complexes become one of the most powerful water sensors known
due to their extraordinary sensitivity, fast response, and wide detection range
for water.
PMID- 28420234
TI - Raman Spectroscopy of Fish Oil Capsules: Polyunsaturated Fatty Acid Quantitation
Plus Detection of Ethyl Esters and Oxidation.
AB - Fish oils are the primary dietary source of omega-3 polyunsaturated fatty acids
(PUFA), but these compounds are prone to oxidation, and commercial fish oil
supplements sometimes contain less PUFA than claimed. These supplements are
predominantly sold in softgel capsules. In this work, we show that Fourier
transform (FT)-Raman spectra of fish oils (n = 5) and omega-3 PUFA concentrates
(n = 6) can be acquired directly through intact softgel (gelatin) capsules. These
spectra could be used to rapidly distinguish supplements containing ethyl esters
from those containing triacylglyceride oils. Raman spectroscopy calibrated with
partial least-squares regression against traditional fatty acid methyl ester
analyses by gas chromatography-mass spectrometry could be used to rapidly and
nondestructively quantitate PUFA and other fatty acid classes directly though
capsules. We also show that FT-Raman spectroscopy can noninvasively detect
oxidation with high sensitivity. Oils with peroxide values of as low as 10 mequiv
kg-1, which are on the cusp of falling outside of specification, could be readily
distinguished from oils that were within specification (7 mequiv kg-1).
PMID- 28420235
TI - Garcinol from Garcinia indica Downregulates Cancer Stem-like Cell Biomarker
ALDH1A1 in Nonsmall Cell Lung Cancer A549 Cells through DDIT3 Activation.
AB - Nonsmall cell lung cancer (NSCLC) is the predominant type of lung cancer.
Patients with NSCLC show high mortality rates because of failure to clean up
cancer stem cells (CSCs). The anticancer activity of phytochemical garcinol has
been identified in various cancer cell models. However, the effect of garcinol on
NSCLC cell lines is still lacking. Of the NSCLC cell lines we tested, A549 cells
were the most sensitive to garcinol. Interestingly, Aldehyde Dehydrogenase 1
Family Member A1 (ALDH1A1) was preferentially expressed in A549 cells and
downregulated by the addition of garcinol. We also found that garcinol enriched
DNA damage-inducible transcript 3 (DDIT3) and then altered DDIT3-CCAAT-enhancer
binding proteins beta (C/EBPbeta) interaction resulting in a decreased binding of
C/EBPbeta to the endogenous ALDH1A1 promoter. Furthermore, garcinol's inhibition
of ALDH1A1 was identified in a xenograft mice model. Garcinol repressed ALDH1A1
transcription in A549 cells through alterations in the interaction between DDIT3
and C/EBPbeta. Garcinol could be a potential dietary phytochemical candidate for
NSCLCs patients whose tumors harbored high ALDH1A1 expression.
PMID- 28420236
TI - Human Hepatocarcinoma Cell Targeting by Glypican-3 Ligand Peptide Functionalized
Silica Nanoparticles: Implications for Ultrasound Molecular Imaging.
AB - Silica nanoparticles (SiNPs) are widely studied nanomaterials for their potential
employment in advanced biomedical applications, such as selective molecular
imaging and targeted drug delivery. SiNPs are generally low cost and highly
biocompatible, can be easily functionalized with a wide variety of functional
ligands, and have been demonstrated to be effective in enhancing ultrasound
contrast at clinical diagnostic frequencies. Therefore, SiNPs might be used as
contrast agents in echographic imaging. In this work, we have developed a SiNPs
based system for the in vitro molecular imaging of hepatocellular carcinoma cells
that express high levels of glypican-3 protein (GPC-3) on their surface. In this
regard, a novel GPC-3 targeting peptide was designed and conjugated to
fluorescent silica nanoparticles. The physicochemical properties, acoustic
behavior, and biocompatibility profile of the functionalized SiNPs were
characterized; then binding and uptake of both naked and functionalized SiNPs
were analyzed by laser scanning confocal microscopy and transmission electron
microscopy in GPC-3 positive HepG2 cells, a human hepatocarcinoma cell line. The
results obtained showed that GPC-3-functionalized fluorescent SiNPs significantly
enhanced the ultrasound contrast and were effectively bound and taken up by HepG2
cells without affecting their viability.
PMID- 28420237
TI - Intrinsic Instability of Cs2In(I)M(III)X6 (M = Bi, Sb; X = Halogen) Double
Perovskites: A Combined Density Functional Theory and Experimental Study.
AB - Recently, there has been substantial interest in developing double-B-cation
halide perovskites, which hold the potential to overcome the toxicity and
instability issues inherent within emerging lead halide-based solar absorber
materials. Among all double perovskites investigated, In(I)-based Cs2InBiCl6 and
Cs2InSbCl6 have been proposed as promising thin-film photovoltaic absorber
candidates, with computational examination predicting suitable materials
properties, including direct bandgap and small effective masses for both
electrons and holes. In this study, we report the intrinsic instability of
Cs2In(I)M(III)X6 (M = Bi, Sb; X = halogen) double perovskites by a combination of
density functional theory and experimental study. Our results suggest that the
In(I)-based double perovskites are unstable against oxidation into In(III)-based
compounds. Further, the results show the need to consider reduction-oxidation
(redox) chemistry when predicting stability of new prospective electronic
materials, especially when less common oxidation states are involved.
PMID- 28420238
TI - The Role of Ti Buffer Layer Thickness on the Resistive Switching Properties of
Hafnium Oxide-Based Resistive Switching Memories.
AB - Ti/HfOx-based resistive random access memory (RRAM) has been extensively
investigated as an emerging nonvolatile memory (NVM) candidate due to its
excellent memory performance and CMOS process compatibility. Although the
importance of the role of the Ti buffer layer is well recognized, detailed
understanding about the nature of Ti thickness-dependent asymmetric switching is
still missing. To realize this, the present work addresses the effects of Ti
buffer layer thickness on the switching properties of TiN/Ti/HfOx/TiN 1T1R RRAM.
Consequently, we have demonstrated a simple strategy to regulate the FORMING
voltage, leakage current, memory window, and decrease the operation current, etc.
by varying the thickness of the Ti layer on the HfOx dielectrics. Accordingly,
controllable and reliable bipolar, complementary, and reverse bipolar resistive
switching (BRS, CRS, and R-BRS) properties have been demonstrated. This work also
provides the direction to avoid unwanted CRS properties during the first RESET
operation by decreasing the FORMING voltage. Furthermore, the memory device shows
good nonvolatility at ~1 MUA programming current by selecting a proper thickness
of Ti buffer layer. To achieve reliable BRS properties for low power application,
the operation current has been further optimized, whereas the memory device shows
pulse endurance of more than 7 million cycles at a low pulse width of 50 ns and
excellent data retention properties of more than 40 h at 150 degrees C
measurement temperature.
PMID- 28420241
TI - Percutaneous endoscopic gastrostomy in high risk ALS: insights to effort to
drawing a risk map.
PMID- 28420243
TI - Quantifying Medical Student Education and Exposure to Otolaryngology.
AB - OBJECTIVES: Evaluate the educational and exposure opportunities provided to
students by national otolaryngology organizations. METHODS: Twenty-four
otolaryngology organizations and subspecialty societies were reviewed for medical
student involvement opportunities, educational and enrichment opportunities,
costs of involvement, and available research and travel scholarships. RESULTS:
Nine organizations (37.5%) offered membership; 6 charged a membership fee,
averaging $73 +/- $30 (mean +/- SD). Membership was limited to associate status
for 7 organizations (77.8%; 7/9). Three organizations (12.5%) provided service
opportunities, 4 (16.7%) allowed students to vote, and 1 (4.2%) allowed students
to endorse others for membership. Most organizations allowed students to attend
conferences (95.8%), and 19 (79.2%) allowed students to present research. Twenty
one (87.5%) organizations charged a conference registration fee ($366 +/- $300).
Seven organizations (29.2%) offered research scholarships, and 5 (20.8%) offered
travel awards. CONCLUSIONS: Opportunities exist for medical students to attend
conferences and present research; however, educational and enrichment activities
in other areas were limited. Future efforts may be warranted to increase the
number and type of opportunities for students.
PMID- 28420242
TI - High prevalence of NDM metallo-beta-lactamase among ESBL-producing Escherichia
coli Isolates.
AB - Resistance to beta-lactams in Enterobacteriaceae has been increasing worldwide.
This study aimed to determine the frequency of beta-lactamase genes and
antibiotic resistance rates of 140 extended-spectrum beta-lactamase (ESBL)
producing Escherichia coli isolates obtained from urinary tract infection in Ordu
Province, Turkey. Isolates were identified by classic methods and by automated
system. ESBL production was confirmed by double disk synergy test and
antimicrobial susceptibility was investigated by disk diffusion method. All
isolates were screened for beta-lactamase coding genes from three groups (A, B,
and D) by polymerase chain reaction. The highest rate of susceptible isolates was
observed for imipenem (IPM, 99.3%) and ertapenem (ETP, 97.9%), and the highest
rate of resistant isolates was observed for cefuroxime (97.9%), ceftriaxone
(97.2%), and cefazolin (90.7%). In our study, blaCTX-M1-like group was the most
prevalent beta-lactamase (n = 109), followed by blaTEM (n = 68), blaCTX-M2 (n =
22), and blaSHV (n = 2). By contrast to low resistance rate to IPM and ETP, we
determined blaNDM in 31 isolates (22.1%). In co-prevalence of blaNDM-1 and ESBL
coding genes, a low carbapenem resistance was determined. We can confirm that
blaCTX-M1-types are still the most frequent beta-lactamase coding gene in Turkey.
Our study showed the highest prevalence of blaNDM-1 metallo-beta-lactamase coding
gene in ESBL-producing E. coli.
PMID- 28420244
TI - Occupation-based practices and homelessness: A scoping review.
AB - BACKGROUND: Persons experiencing or at risk of homelessness have occupational
needs that are seldom addressed in the Canadian system of care. The lack of
documented evidence on occupational therapy practices in this field hinders the
development of the profession. PURPOSE: This article identifies current and
potential practices that aim to enable or support the occupations of persons
experiencing or at risk of homelessness. METHOD: A scoping review was conducted,
including evidence from both occupational therapy and non-occupational therapy
sources. FINDINGS: One hundred and seventy-eight papers were selected in the
areas of occupational performance skills training, enrichment of occupational
repertoire, employment/education, physical rehabilitation services, child/family
services, community building, occupational transition from homeless to housed,
literacy, and disaster relief. IMPLICATIONS: Occupational therapists can build
environments and create opportunities that facilitate occupational engagement of
individuals experiencing homelessness. Gaps in knowledge include the evaluation
of occupational therapy practices, the Canadian context of family homelessness,
and the cultural safety of occupational therapy interventions.
PMID- 28420245
TI - A first approach to a neuropsychological screening tool using eye-tracking for
bedside cognitive testing based on the Edinburgh Cognitive and Behavioural ALS
Screen.
AB - OBJECTIVE: Reliable assessment of cognitive functions is a challenging task in
amyotrophic lateral sclerosis (ALS) patients unable to speak and write. We
therefore present an eye-tracking based neuropsychological screening tool based
on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a standard
screening tool for cognitive deficits in ALS. METHODS: In total, 46 ALS patients
and 50 healthy controls matched for age, gender and education were tested with an
oculomotor based and a standard paper-and-pencil version of the ECAS. RESULTS:
Significant correlation between both versions was observed for ALS patients and
healthy controls in the ECAS total score and in all of its ALS-specific domains
(all r > 0.3; all p < 0.05). The eye-tracking version of the ECAS reliably
distinguished between ALS patients and healthy controls in the ECAS total score
(p < 0.05). Also, cognitively impaired and non-impaired patients could be
reliably distinguished with a specificity of 95%. CONCLUSION: This study provides
first evidence that the eye-tracking based ECAS version is a promising approach
for assessing cognitive deficits in ALS patients who are unable to speak or
write.
PMID- 28420246
TI - Husband's Reaction to His Wife's Sexual Rejection Is Predicted by the Time She
Spends With Her Male Friends but Not Her Male Coworkers.
AB - Males among many species, including humans, evaluate cues of sperm competition
risk and adjust accordingly their sperm competition tactics. The number of
potential sexual rivals can serve as an index of sperm competition risk.
Therefore, men may adjust their in-pair copulatory interest in accordance with
the presence of sexual rivals. Using self-reports from 45 married men, we test
the hypotheses that the time a man's wife spends with other men-either male
friends or male coworkers-will positively predict a man's copulatory interest in
his wife (Hypothesis 1) and his anger (Hypothesis 2), upset (Hypothesis 3), and
frustration (Hypothesis 4) in response to his wife's sexual rejection. The
results show that the time wives spend with male friends (but not male coworkers)
predicts their husbands' anger, upset, and frustration in response to sexual
rejection, providing support for Hypotheses 2-4. Discussion highlights novel
contributions of the current research and provides a potential explanation for
the discrepant findings regarding male friends versus male coworkers.
PMID- 28420247
TI - Clinical and radiological outcomes after decompression and posterior fusion in
patients with degenerative scoliosis.
AB - OBJECTIVE: The prevalence of degenerative scoliosis (DS) increases with age and
an overall increase is seen due to the aging population. This study aims to
evaluate the clinical and radiological outcomes after decompression and posterior
fusion in patients with DS. METHODS: In this is prospective study, 43 patients
with DS, aged 37 to 70 years, were eligible to undergo decompression and
posterior fusion. Primary outcomes were low back pain (LBP) with or without
radicular pain, which was evaluated preoperatively and at 12 and 24 months after
surgery with the use of a visual analog scale (VAS), and the quality of life
(QOL), which was assessed at the same time periods by the Oswestry Disability
Index (ODI) questionnaire. The Cobb's method was used to measure the degree of
scoliosis in each patient preoperatively and at 24 hours, 12 and 24 months after
the surgery. RESULTS: VAS scores improved significantly from a mean of 8.18
preoperatively to 4.48 at 12 months and 3.07 at 24 months postoperatively (P <
.001). The mean radicular pain scores also decreased significantly (P < .001). At
postoperative 12 months, the mean ODI score was significantly lower than the mean
preoperative ODI score (47.81 +/- 16.06 vs. 72.18 +/- 12.28; P = .001). ODI score
at 24 months postoperatively was significantly better than the preoperative ODI
(15.53 +/- 7.21 vs. 72.18 +/- 12.28; P = .016). The mean Cobb angle changed
significantly from 31.4 degrees +/- 4.88 preoperatively to 3.28 degrees +/-
2.10 at 24 months postoperatively (P < .001). CONCLUSIONS: Our findings suggest
that decompression and posterior fusion in the patients with DS is an effective
surgical method which is associated with satisfying clinical results in terms of
improvement of postoperative LBP, radicular pain, and QOL, and correction of Cobb
angle at 12 and 24 months after the surgery and restoration of sagittal alignment
at 2 months postoperatively.
PMID- 28420248
TI - Creating an Optimal 3D Printed Model for Temporal Bone Dissection Training.
AB - OBJECTIVE: Making a 3-dimensional (3D) temporal bone model is simple using a
plaster powder bed and an inkjet printer. However, it is difficult to reproduce
air-containing spaces and precise middle ear structures. The objective of this
study was to overcome these problems and create a temporal bone model that would
be useful both as a training tool and for preoperative simulation. METHODS:
Drainage holes were made to remove excess materials from air-containing spaces,
ossicle ligaments were manually changed to bony structures, and small and/or soft
tissue structures were colored differently while designing the 3D models. The
outcomes were evaluated by 3 procedures: macroscopic and endoscopic inspection of
the model, comparison of computed tomography (CT) images of the model to the
original CT, and assessment of tactile sensation and reproducibility by 20
surgeons performing surgery on the model. RESULTS: Macroscopic and endoscopic
inspection, CT images, and assessment by surgeons were in agreement in terms of
reproducibility of model structures. Most structures could be reproduced, but the
stapes, tympanic sinus, and mastoid air cells were unsatisfactory. Perioperative
tactile sensation of the model was excellent. CONCLUSIONS: Although this model
still does not embody perfect reproducibility, it proved sufficiently practical
for use in surgical training.
PMID- 28420249
TI - Increasing HIV testing among pregnant women in Nigeria: evaluating the
traditional birth attendant and primary health center integration (TAP-In) model.
AB - Engaging Traditional Birth Attendants (TBAs) may be critical to preventing mother
to-child transmission of HIV (PMTCT) in Nigeria. We integrated TBAs into Primary
Health Centers (PHCs) and provided the TBAs with HIV counseling and testing (HCT)
training for PMTCT (TAP-In). The purpose of this study was to evaluate the impact
of TAP-In on HCT uptake among pregnant women. A quasi-experimental design was
used for this study. Twenty PHCs were assigned to the intervention group that
integrated TAP-In and 20 were assigned to the control group. Data were collected
six months prior to the initiation of TAP-In and six months post, using antenatal
clinic registries. Intervention PHCs more than doubled the number of pregnant
women who received HCT in their catchment area post TAP-In while control PHCs had
no significant change. After initiating TAP-In, intervention PHCs provided almost
three times more HCT than the control PHCs (p < 0.01) with TBA provided over half
of the HCT post TAP-In. The TAP-In model was effective for increasing HCT among
pregnant women.
PMID- 28420251
TI - Differential Diagnosis of Diaper Dermatitis.
AB - Mild diaper dermatitis often occurs in children before toilet training is
complete, particularly from 9 to 12 months of age, and the most common
presentation is an irritant contact dermatitis. Diaper dermatitis may account for
up to 25% of dermatology visits to health care providers during the first year of
life. Fortunately, since the introduction of hypoallergenic, superabsorbent
modern disposable diapers, the incidence and severity of irritant and allergic
contact dermatitis has decreased dramatically. Diaper dermatitis broadly refers
to skin disorders that occur in the diaper area, such as skin eruptions triggered
by diapers, rashes exacerbated by the diaper, and other events that occur in the
diaper area. A number of skin conditions that can occur anywhere on the skin may
present with distinctive findings in the diaper area. The following discussion
will review the most common triggers of diaper dermatitis and contact irritant
dermatitis, while focusing on the skin conditions that may be associated or
overlap clinically with contact dermatitis.
PMID- 28420252
TI - Diaper Dermatitis: Facts and Misinformation.
PMID- 28420250
TI - The European Association of Preventive Cardiology Exercise Prescription in
Everyday Practice and Rehabilitative Training (EXPERT) tool: A digital training
and decision support system for optimized exercise prescription in cardiovascular
disease. Concept, definitions and construction methodology.
AB - Background Exercise rehabilitation is highly recommended by current guidelines on
prevention of cardiovascular disease, but its implementation is still poor. Many
clinicians experience difficulties in prescribing exercise in the presence of
different concomitant cardiovascular diseases and risk factors within the same
patient. It was aimed to develop a digital training and decision support system
for exercise prescription in cardiovascular disease patients in clinical
practice: the European Association of Preventive Cardiology Exercise Prescription
in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT
working group members were requested to define (a) diagnostic criteria for
specific cardiovascular diseases, cardiovascular disease risk factors, and other
chronic non-cardiovascular conditions, (b) primary goals of exercise
intervention, (c) disease-specific prescription of exercise training (intensity,
frequency, volume, type, session and programme duration), and (d) exercise
training safety advices. The impact of exercise tolerance, common cardiovascular
medications and adverse events during exercise testing were further taken into
account for optimized exercise prescription. Results Exercise training
recommendations and safety advices were formulated for 10 cardiovascular
diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes,
obesity, hypertension, hypercholesterolaemia), and three common chronic non
cardiovascular conditions (lung and renal failure and sarcopaenia), but also
accounted for baseline exercise tolerance, common cardiovascular medications and
occurrence of adverse events during exercise testing. An algorithm, supported by
an interactive tool, was constructed based on these data. This training and
decision support system automatically provides an exercise prescription according
to the variables provided. Conclusion This digital training and decision support
system may contribute in overcoming barriers in exercise implementation in common
cardiovascular diseases.
PMID- 28420253
TI - Myths on Chemical Burns in the Diaper Area.
AB - Over the past several years, a number of articles and online posts have
circulated on the Internet associating use of disposable and cloth diapers with
chemical burns on babies' skin. Because both mild chemical burns and diaper
dermatitis (diaper rash) can cause skin redness and peeling, it is not surprising
that some confusion has arisen regarding the association between these two
conditions. However, diapers cannot cause chemical burns because they are made of
inert materials. Diaper rash and chemical burns are distinct conditions that
require different evaluation and treatment, which is why it is important for
pediatricians to help parents understand the difference.
PMID- 28420254
TI - Common Diaper Ingredient Questions: Modern Disposable Diaper Materials Are Safe
and Extensively Tested.
AB - Today's disposable diapers are high-performance and well-tested products,
designed to keep skin dry and healthy. They are primarily made of biologically
inert polymers, commonly used in fabrics and other materials that are in contact
with skin, and in foods and cosmetics. Still, product safety and ingredients in
everyday products can be a source of anxiety for new parents. This article
provides the facts behind some commonly asked questions from consumers about
diaper ingredients and safety, including myths and facts related to chlorine,
latex, dyes, and chemical additives.
PMID- 28420255
TI - Chemical and Common Burns in Children.
AB - Burns are a common cause of preventable morbidity and mortality in children.
Thermal and chemical burns are the most common types of burns. Their clinical
appearance can be similar and the treatment is largely similar. Thermal burns in
children occur primarily after exposure to a hot surface or liquid, or contact
with fire. Burns are typically classified based on the depth and total body
surface area, and the severity and onset of the burn can also depend on the
temperature and duration of contact. Chemical burns are caused by chemicals-most
commonly acids and alkalis-that can damage the skin on contact. In children, the
most common cause of chemical burns is from household products such as toilet
bowl cleaners, drain cleaners, detergents, and bleaches. Mild chemical burns
generally cause redness and pain and can look similar to other common rashes or
skin infections, whereas severe chemical burns are more extreme and may cause
redness, blistering, skin peeling, and swelling.
PMID- 28420256
TI - Accuracy of a Pediatric Behavioral Health Screener to Detect Untreated Behavioral
Health Problems in Primary Care Settings.
AB - An estimated 10% to 20% of youth in primary care exhibit behavioral symptoms and
may go underdetected. Most screeners identify risk base of symptoms alone,
irrespective of functional impairment. To address this issue, the Pediatric
Symptom Checklist-17 (PSC-17), a widely used symptom screener, was combined with
functional impairment and current behavioral services enrollment items to form
the Pediatric Behavioral Health Screen (PBHS) and assessed compared to the full
Child Behavior Checklist (CBCL). A total of 267 youth between 6 and 16 years of
age were administered the screener and the CBCL. Areas under the receiver
operating curves approached or exceeded 0.90 in all analyses, reflecting
excellent classification accuracy. Almost no false negatives were observed among
currently untreated cases with functional impairment. No differential item
functioning was found. Performance of the PSC-17 as a pediatric primary care
behavioral health screener supported previous research, and additional functional
impairment items to form the PBHS appeared useful, particularly for interpreting
borderline range scores.
PMID- 28420257
TI - Gestational Diabetes Management Using Smart Mobile Telemedicine.
AB - Gestational diabetes (GDM) burden has been increasing progressively over the past
years. Knowing that intrauterine exposure to maternal diabetes confers high risk
for macrosomia as well as for future type 2 diabetes and obesity of the
offspring, health care organizations try to provide effective control in spite of
the limited resources. Artificial-intelligence-augmented telemedicine has been
proposed as a helpful tool to facilitate an efficient widespread medical
assistance to GDM. The aim of the study we present was to test the feasibility
and acceptance of a mobile decision-support system for GDM, developed in the
seventh framework program MobiGuide Project, which includes computer
interpretable clinical practice guidelines, access to data from the electronic
health record as well as from glucose, blood pressure, and activity sensors. The
results of this pilot study with 20 patients showed that the system is feasible.
Compliance of patients with blood glucose monitoring was higher than that
observed in a historical group of 247 patients, similar in clinical
characteristics, who had been followed up for the 3 years prior to the pilot
study. A questionnaire on the use of the telemedicine system showed a high degree
of acceptance.
PMID- 28420258
TI - Lace Up for Healthy Feet: The Impact of Shoe Closure on Plantar Stress Response.
AB - OBJECTIVE: This study examined the impact of shoe closure on plantar thermal
stress response (TSR), which is known to be a surrogate of shear stress and skin
perfusion. It is aimed to explore potential impact of shoe closure on increasing
risk factors associated with plantar ulcers in people with diabetic peripheral
neuropathy (DPN). METHODS: Fifteen eligible subjects were enrolled. The left foot
was used as a reference and fitted to a self-adjusted and habitual lace
tightening method by each subject. The right foot was used as a test closure and
fitted into three lace closure conditions: loose, tight, and preset optimal
closure (reel clutch, BOA technology). Thermal images were taken after 5 minutes
of acclimatization (pre-trial) and immediately after 200 walking steps in each
shoe closure condition (post-trial). TSR was calculated from the thermal images.
RESULTS: TSR was significantly higher in the test closure with loose (70.24%, P =
.000) and tight (66.85%, P = .007) and lower (-206.53%, P = .000) in the preset
optimal closure when compared to the reference closure. Only lace closure
conditions affected TSR with no significant impact from age, BMI, and gender in
our sample in a multivariable regression model. CONCLUSION: The results from this
study suggest that shoelace closure technique can have a profound effect on TSR.
It therefore stands to reason that optimal lace closure may have an impact in
reducing risk of plantar ulcers in people with DPN. Interestingly, results
revealed that even a self-adjusted lace closure may not be necessarily optimal
and a preset closure setting like reel clutch might ultimately be recommended to
minimize risk. Further study is warranted to confirm or refute these interesting
results.
PMID- 28420259
TI - Seasonality of Insulin Use in German Outpatients With Diabetes: A Retrospective
Analysis.
AB - BACKGROUND: Seasonality in insulin sensitivity has been the focus of
controversial literature in the past decades. The aim of this study was to
analyze seasonality of insulin use in patients with diabetes who were followed in
German general practices. METHODS: This study included patients affected by type
1 (T1DM) or type 2 diabetes mellitus (T2DM) who received intensified conventional
insulin therapy over a period of at least 12 months between 2013 and 2015. The
main outcome was the median insulin dose per day (calculated daily insulin doses,
CDDs) between June and August (summer) and between December and February
(winter). RESULTS: The present study included 1197 T1DM patients and 3836 T2DM
patients from 492 general practitioner or diabetologist practices. The mean age
was 45.4 years (SD = 16.2 years) in the T1DM group and 65.2 years (SD = 14.1
years) in the T2DM group. The most frequent basal insulin therapy was insulin
glargine (T1DM: 45.7%; T2DM: 41.1%), and the most frequent bolus insulin therapy
was insulin lispro in the T1DM group (38.7%) and human insulin in the T2DM group
(45.2%). The consumption of basal and bolus insulins did not significantly differ
between summer and winter in T1DM individuals (basal therapy: 30.8 international
units (IU)/day versus 31.2 IU/day; bolus therapy: 39.4 IU/day versus 37.8
IU/day). This consumption was also similar between the two seasons in the T2DM
group (basal therapy: 31.0 IU/day versus 30.6 IU/day; bolus therapy: 44.3 IU/day
versus 44.1 IU/day). CONCLUSIONS: There was no significant difference in the use
of basal and bolus insulin therapies between summer and winter in German patients
with T1DM or T2DM.
PMID- 28420260
TI - The Safety of Nonadjunctive Use of Continuous Glucose Monitors for Insulin
Dosing: Still Not Resolved.
PMID- 28420261
TI - Added Value of Early Literacy Screening in Preschool Children.
AB - The Early Literacy Screener (ELS) is a brief screen for emergent literacy delays
in 4- and 5-year-olds. Standard developmental screens may also flag these
children. What is the value of adding the ELS? Parents of children aged 4 (n =
45) and 5 (n = 26) years completed the Ages and Stages Questionnaire-3 (ASQ-3),
the Survey of Well-Being in Young Children (SWYC), and the ELS. Rates of positive
agreement (PA), negative agreement (NA), and overall agreement (Cohen's kappa)
across the various screening tools were calculated. Early literacy delays were
detected in 51% of those who passed the ASQ and 38% of those who passed the SWYC.
For ELS versus ASQ, kappa = 0.18, PA = 0.36 (95% CI = 0.23-0.51), and NA = 0.83
(95% CI = 0.66-0.92). For ELS versus SWYC, kappa = 0.42, PA = 0.61 (95% CI = 0.45
0.75), and NA = 0.82 (95% CI = 0.65-0.92). The ELS adds value by flagging early
literacy delays in many children who pass either the ASQ-3 or SWYC.
PMID- 28420262
TI - Impact of an Educational Intervention to Improve Physician Adherence to
Bronchiolitis Clinical Practice Guidelines: A Pre-Post Intervention Study.
AB - Bronchiolitis is the leading cause of infant hospitalizations in the United
States. Despite clinical practice guidelines discouraging the utilization of non
evidence-based therapies, there continues to be wide variation in care and
resource utilization. A pre-post physician focused educational intervention was
conducted with the aims to reduce the use of non-evidence-based medical
therapies, including bronchodilators, among patients admitted for bronchiolitis.
Among patients meeting inclusion criteria (pre: n = 45; post: n = 47),
bronchodilator use decreased by 50% ( P < .001). Antibiotic use increased by 9% (
P < .02), although results remained within published acceptable utilization rates
of less than 19%. There were no statistical differences in chest X-ray,
respiratory viral panel, and steroid use. There were no differences in number of
pediatric intensive care unit transfers, 30-day readmission rates, and mean
length of stay. The findings demonstrate that a physician-focused educational
intervention highlighting American Academy of Pediatrics clinical practice
guidelines resulted in reduced utilization of bronchodilators.
PMID- 28420263
TI - An Unusual Cause of Frequent, Sudden, Transient, Unexplained Falls and New-Onset
Status Epilepticus: Case Report and Mini-Review.
AB - We report a 14-year old adolescent Caucasian female, who presented with frequent,
sudden, transient, and unexplained falls leading to multiple serious injuries to
her head and extremities requiring several visits to the emergency department.
She was evaluated numerous times and imaging studies, echocardiogram,
electrocardiogram, and electroencephalogram studies were all normal. She
eventually presented to outside emergency department with dystonic posturing and
status epilepticus and was transferred to our pediatric intensive care unit for
further management. She was diagnosed with an uncommon, underrecognized and
underdiagnosed condition. To our knowledge there is no such previous report in a
pediatric patient.
PMID- 28420264
TI - The Rate of Sepsis in a National Pediatric Population, 2006 to 2012.
AB - INTRODUCTION: The rate of pediatric severe sepsis is reported to be on the rise
in the United States, increasing by approximately 6000 cases annually. The goal
of this study was to determine the rate of pediatric sepsis per 100 000 inpatient
discharges over time. METHODS: The 2006, 2009, and 2012 Agency for Healthcare
Research and Quality Healthcare Cost Utilization Project Kid's Inpatient
Databases were used to analyze the rate of sepsis in children over time. RESULTS:
The rate of pediatric sepsis has increased over time from 92.8 per 100 000 in
2006 to 158.7 per 100 000 in 2012. Children less than a year old with Medicaid
coverage and 3 or more procedures during hospitalization have significantly
higher rates than their counterparts. CONCLUSIONS: This study helps clarify the
population demographics that are at greater risk for sepsis infections.
Understanding the at-risk population aids policymakers and care providers in
targeting these populations and make drastic changes to sepsis policies.
PMID- 28420265
TI - iCHAMPSS: Usability and Psychosocial Impact for Increasing Implementation of
Sexual Health Education.
AB - INTRODUCTION: Diffusion of sexual health evidence-based programs (EBPs) in
schools is a complex and challenging process. iCHAMPSS ( CHoosing And Maintaining
effective Programs for Sex education in Schools) is an innovative theory- and Web
based decision support system that may help facilitate this process. The purpose
of this study was to pilot-test iCHAMPSS for usability and short-term
psychosocial impact. METHOD: School district stakeholders from across Texas were
recruited ( N = 16) and given access to iCHAMPSS for 3 weeks in fall 2014. Pre-
and posttests were administered to measure usability parameters and short-term
psychosocial outcomes. Data were analyzed using descriptive statistics and the
Wilcoxon signed-rank test. RESULTS: Most participants reported that iCHAMPSS was
easy to use, credible, helpful, and of sufficient motivational appeal. iCHAMPSS
significantly increased participants' self-efficacy to obtain approval from their
board of trustees to implement a sexual health EBP. Positive, though
nonsignificant, trends included increased knowledge to locate EBPs, skills to
prioritize sexual health education at the district level, and ability to choose
an EBP that best meets district needs. CONCLUSIONS: iCHAMPSS is an innovative
decision support system that could accelerate uptake of EBPs by facilitating
diffusion and advance the field of dissemination and implementation science for
the promotion of sexual health EBPs.
PMID- 28420266
TI - Lessons Learned From the Field-Testing of Healthy Love: An HIV Prevention
Intervention for Black Women.
AB - BACKGROUND: Healthy Love is a brief, highly interactive, single-session, group
level HIV prevention intervention designed for African American women that is
effective at reducing sex risk behaviors and increasing condom use and HIV
testing among participants. The Centers for Disease Control and Prevention,
through a contract, developed a user-friendly intervention package that would
allow organizations to adopt and implement Healthy Love with fidelity. METHOD:
Training and implementation materials were developed to support original research
protocols, and piloted and revised to conduct field-testing with case study
agencies (CSAs). Three CSAs were selected to deliver the intervention over a 3
month period to test the utility of intervention materials and feasibility of
implementation. RESULTS: All CSAs were able to successfully deliver 10 sessions
with a total of 185 women ranging from 18 to 59 years of age. Successes and
challenges encountered in training, preimplementation activities, and
intervention delivery are described. DISCUSSION: Lessons learned from training,
technical assistance, and process monitoring and evaluation informed final
package revisions. Research to practice recommendations are shared as is guidance
for future implementations of Healthy Love. The research to practice process used
is a model approach for developing a comprehensive intervention package and will
support the adoption of Healthy Love by other organizations.
PMID- 28420267
TI - Promoting Health Through Policy and Systems Change: Public Health Students and
Mentors on the Value of Policy Advocacy Experience in Academic Internships.
AB - Emerging professionals and new Certified Health Education Specialists often lack
academic training in and actual experience in National Commission for Health
Education Credentialing Area of Responsibility VII: Communicate, Promote, and
Advocate for Health, Health Education/Promotion, and the Profession. For
undergraduate and graduate students who have an opportunity to complete an
internship or practicum experience, gaining experience in Competencies 7.2:
Engage in advocacy for health and health education/promotion and 7.3: Influence
policy and/or systems change to promote health and health education can have a
profound impact on their career development and their ability to advocate for
policies that promote health and health equity. Compelling evidence suggests that
interventions that address social determinants of health such as poverty and
education and those that change the context through improved policy or healthier
environments have the greatest impact on public health, making it vital for
emerging public health professionals to gain experience in policy advocacy and
systems change. In this commentary, students and faculty from two large
universities in the U.S.-Mexico border region reflect on the value of policy
advocacy in academic internship/fieldwork experiences. Based on their
experiences, they highly recommend that students seek out internship
opportunities where they can participate in policy advocacy, and they encourage
university faculty and practicum preceptors to provide more opportunities for
policy advocacy in both classroom and fieldwork settings.
PMID- 28420269
TI - Strengthening Social Ties to Increase Confidence and Self-Esteem Among Sexual and
Gender Minority Youth.
AB - Sexual and gender minority (SGM) youth too often live in nonsupportive
environments. This study reports the influence of social support from primary and
secondary social ties on confidence and self-esteem among participants in Hatch
Youth, a drop-in group-level intervention for SGM youth. Each 3-hour Hatch Youth
meeting consists of a social, educational, and youth-led support hour. Over 14
weeks, these meetings were randomly observed and individual interviews with
participating youth ( n = 12) and staff and volunteers ( n = 12) were conducted;
data underwent a content analysis. Participants perceived an increase in
confidence and self-esteem through enhanced bonding with family and friends, a
sense of belonging, and community empowerment because of their involvement with
Hatch Youth, suggesting drop-in centers can strengthen secondary social ties and
improve confidence and self-esteem.
PMID- 28420270
TI - Stages of change in audiology: comparison of three self-assessment measures.
AB - OBJECTIVE: In a clinical setting, theories of health behaviour change could help
audiologists and other hearing health care professionals understand the barriers
that prevent people with hearing problems to seek audiological help. The
transtheoretical (stages of change) model of health behaviour change is one of
these theories. It describes a person's journey towards health behaviour change
(e.g. seeking help or taking up rehabilitation) in separate stages:
precontemplation, contemplation, preparation, action, and, finally, maintenance.
A short self-assessment measure of stages of change may guide the clinician and
facilitate first appointments. This article describes correlations between three
stages of change measures of different lengths, one 24-item and two one-item.
DESIGN: Participants were recruited through an online hearing screening study.
Adults who failed the speech-in-noise recognition screening test and who had
never undergone a hearing aid fitting were invited to complete further
questionnaires online, including the three stages of change measures. STUDY
SAMPLE: In total, 224 adults completed the three measures. RESULTS: A majority of
the participants were categorised as being in one of the information- and help
seeking stage of change (contemplation or preparation). The three stages of
change measures were significantly correlated. Conclusions Our results support
further investigating the use of a one-item measure to determine stages of change
in people with hearing impairment.
PMID- 28420271
TI - Imaging TMS: antidepressant mechanisms and treatment optimization.
AB - With the antidepressant efficacy of Transcranial Magnetic Stimulation well
established by several meta-analyses, there is growing interest in its mechanism
of action. TMS has been shown to engage, and in some cases, normalize functional
connectivity and neurotransmitter levels within networks dysfunctional in the
depressed state. In this review, I will suggest candidate biomarkers, based on
neuroimaging, that may be predictive of response to TMS. I will then review the
effects of TMS on networks and neurotransmitter systems involved in depression.
Throughout, I will also discuss how our current understanding of response
predication and network engagement may be used to personalize treatment and
optimize its efficacy.
PMID- 28420273
TI - Role of inflammation in the association between the western dietary pattern and
metabolic syndrome among Lebanese adults.
AB - : The aim of this study was to investigate whether inflammation mediates the
previously observed direct association between the western dietary pattern (WDP)
and metabolic syndrome (MetS) among Lebanese adults. Sociodemographic, lifestyle,
dietary pattern scores, anthropometric and biochemical data of 331 adults were
used in this study. Inflammation indicators considered were: serum C-reactive
protein (CRP) and the dietary inflammatory index (DII). The scores of the WDP
were significantly associated with DII (r = .64) but not with serum CRP. Higher
CRP levels increased the odds of MetS and four out of five of its components,
while no association was found between the DII and MetS. CONCLUSION: The findings
of this study confirmed the association of serum CRP with MetS but did not
support mediation effect of inflammation on the association between the WDP and
MetS. These findings are important to direct future investigations on diet,
inflammation and association with diseases risk.
PMID- 28420272
TI - Resveratrol suppresses hyperoxia-induced nucleocytoplasmic shuttling of SIRT1 and
ROS production in PBMC from preterm infants in vitro.
AB - OBJECTIVE: By assessing silent mating-type information regulation 2 homolog 1
(SIRT1) nucleocytoplasmic shuttling and reactive oxygen species (ROS) levels in
peripheral blood mononuclear cells (PBMCs), this study aimed to explore the role
of SIRT1 in premature infants after exposure to hyperoxia and assess the
protective effects of resveratrol (Res). METHODS: Firstly, ROS levels as well as
SIRT1 translocation and expression in PBMCs samples were evaluated from 40
premature infants with different oxygen amounts received at birth. Then, PBMCs,
from additional 40 premature infants administered no oxygen at birth, were used
to establish an in vitro model of hyperoxia. RESULTS: In infants that received O2
at birth, ROS and MDA levels, and SIRT1 translocation rates gradually increased
in a concentration-dependent manner, while SIRT1 gradually decreased. In
agreement, PBMCs cultured in vitro showed increased ROS levels after exposed to
hyperoxia, SIRT1 translocation increased as well. However, treatment with Res
resulted in opposite effects. CONCLUSION: Res inhibits ROS release in PBMCs from
preterm infants exposed to hyperoxia, likely by preventing SIRT1
nucleocytoplasmic shuttling and increasing SIRT1 expression.
PMID- 28420274
TI - Comparison of serum folate, 25-OH vitamin D, and calcium levels between pregnants
with and without fetal anomaly of neural tube origin.
AB - AIM: The aim of this study was to compare serum folate, vitamin B12, 25-OH
vitamin D, and calcium levels between pregnants with and without fetal anomaly of
neural tube origin. METHODS: One hundred seventy-eight pregnants were recruited
for this study. Pregnants with and without sonographically detected fetal anomaly
of neural tube origin were compared in terms of serum folate, vitamin B12, 25-OH
vitamin D, and calcium levels. RESULTS: There were significant differences
between groups with regard to age, serum 25 OH vitamin D, 1,25 OH vitamin D,
folate, calcium, and B 12 levels. Multivariate regression analyses revealed
significant associations between the serum 25 OH vitamin D level, age, and the
neural tube defect (NTD). CONCLUSIONS: Vitamin D and the age of pregnants were
significantly associated with the NTDs.
PMID- 28420275
TI - Beta Hebbian Learning as a New Method for Exploratory Projection Pursuit.
AB - In this research, a novel family of learning rules called Beta Hebbian Learning
(BHL) is thoroughly investigated to extract information from high-dimensional
datasets by projecting the data onto low-dimensional (typically two dimensional)
subspaces, improving the existing exploratory methods by providing a clear
representation of data's internal structure. BHL applies a family of learning
rules derived from the Probability Density Function (PDF) of the residual based
on the beta distribution. This family of rules may be called Hebbian in that all
use a simple multiplication of the output of the neural network with some
function of the residuals after feedback. The derived learning rules can be
linked to an adaptive form of Exploratory Projection Pursuit and with artificial
distributions, the networks perform as the theory suggests they should: the use
of different learning rules derived from different PDFs allows the identification
of "interesting" dimensions (as far from the Gaussian distribution as possible)
in high-dimensional datasets. This novel algorithm, BHL, has been tested over
seven artificial datasets to study the behavior of BHL parameters, and was later
applied successfully over four real datasets, comparing its results, in terms of
performance, with other well-known Exploratory and projection models such as
Maximum Likelihood Hebbian Learning (MLHL), Locally-Linear Embedding (LLE),
Curvilinear Component Analysis (CCA), Isomap and Neural Principal Component
Analysis (Neural PCA).
PMID- 28420276
TI - The influence of maternal vaginal flora on the intestinal colonization in
newborns and 3-month-old infants.
AB - AIM: The role of maternal vaginal bacteria on the colonization of neonatal gut is
still a matter of discussion. Our aim was to estimate the role of maternal
vaginal flora on the development of intestinal flora in neonates and 3-month-old
infants. METHODS: Seventy-nine maternal-neonatal pairs were included in the
study. Vaginal swabs were taken before the rupture of membranes after admission
to the delivery ward. First neonatal stool (meconium) and stool at 3-month-old
infants were collected and cultured. All samples were subjected to
microbiological analysis for Streptococcus, Staphylococcus, Bifidobacterium,
Clostridium (including C. difficile), Lactobacillus, Escherichia coli, Klebsiella
pneumoniae, and Candida. RESULTS: Maternal vagina was colonized mainly by
streptococci (67%) followed by lactobacilli (58%) and Candida spp. (39%). Vaginal
streptococci influenced the intestinal colonization in infants with
staphylococci, C. difficile, and candida. CONCLUSION: Vaginal lactobacilli
influenced colonization with C. difficile, and Candida. Vaginal flora is a potent
factor influencing the development of bacterial flora in the neonatal and
infantile gut. The extension of the observation period until 3 months of life
allow to discover the potential changes in the intestinal flora of children.
PMID- 28420277
TI - Device optimised chirp stimulus for ABR measurements with an active middle ear
implant.
AB - OBJECTIVE: Active middle ear implants are widely used to treat adults and
children with sensorineural, conductive, or mixed hearing loss. Currently, there
is no adequate method to determine the performance of active middle ear implant
systems. DESIGN: The proposed method is based on measuring the auditory brainstem
response while stimulating the hearing system via the active middle ear implant
(Vibrant SoundbridgeTM, VSB; MEDEL, Austria). The acoustic stimulation was
achieved via an optimised chirp stimulus (CE-Chirp), implemented in the Eclipse
system (Interacoustics, Denmark). To compensate for the frequency-specific delays
in the VSB system, the underlying model function of the CE-Chirp was adjusted
accordingly (VSB-CE-Chirp). Study samples: The study includes 12 subjects having
mild to profound sensorineural, conductive or mixed hearing loss. RESULTS: The
use of an optimised VSB-CE-Chirp instead of the CE-Chirp increases significantly
the ABR wave V amplitudes (1.63 times) and so also increases their
identifiability (by 15.2%). On average, wave V could be identified at a 7.5 dB
lower stimulation level. CONCLUSION: The constructed VSB-CE-Chirp stimulus, after
it had been transmitted through the VSB system, follows well the shape of the
original CE-Chirp. Preliminary measurements in VSB patients demonstrated a
significantly improved ABR amplitude with the VSB-CE-Chirp.
PMID- 28420278
TI - Audiometric features in young adults with Turner syndrome.
AB - OBJECTIVE: Hearing loss (HL) is a known problem in adults with Turner syndrome
(TS). The aim of this study was to investigate audiometric features in young
adults with TS and the extent of hearing aid provision. DESIGN: Patients were
recruited from the Turner centre at Karolinska University Hospital. Analysis of
audiograms was made in relation to hearing aid use, a Swedish normal hearing
cohort and the need for hearing rehabilitation. STUDY SAMPLE: Sixty-four women
with TS aged 25-38 years at the time of their audiological testing. RESULTS:
Fifty-two percent had impaired hearing in at least one ear. Sensorineural hearing
loss (SNHL) was the most common type of HL, most often characterised by a high
frequency loss and/or a mid-frequency dip. Conductive HL was uncommon in young
adults with TS, even though 47 percent were otitis prone as children. Eight of 64
women had previously been fitted with hearing aids. CONCLUSIONS: There is
undoubtedly a need for hearing rehabilitation in young adults with TS. Questions
about hearing must be asked by all doctors treating women with TS to identify
those in need for hearing rehabilitation, even if they have an audiogram with a
normal pure tone average.
PMID- 28420279
TI - Responses of blood mononucleated cells and clinical outcome of non-celiac gluten
sensitive pediatric patients to various cereal sources: a pilot study.
AB - Non-celiac gluten sensitivity (NCGS) is a clinical entity recently documented by
the scientific community in pediatric patients. Nevertheless, its triggering
mechanisms remain largely unsettled. We studied 11 children with NCGS who were
diagnosed based on a clear-cut relationship between wheat consumption and
development of symptoms, after excluding celiac disease (CD) and wheat allergy,
matched with 18 children with active CD. Sixteen pediatric patients were also
enrolled as controls. Cultured peripheral blood mononucleated cells (PBMCs)
obtained from NCGS, CD and control patients were cultured in the presence of
wheat proteins extracted from ancient and modern cultivars. Results demonstrated
that wheat proteins induced an overactivation of the proinflammatory chemokine
CXCL10 in PBMC from NCGS pediatric patients and that this overexpression also
depended on the wheat cultivar from which proteins were extracted. Proteins from
modern wheat cultivar activated CXCL10 to a greater extent than those extracted
from ancient wheat genotypes.
PMID- 28420280
TI - Enteric-coated budesonide for the induction and maintenance of remission of
Crohn's disease in children.
AB - OBJECTIVE: These studies evaluated the safety and efficacy of enteric-coated
budesonide for the induction and maintenance of remission of mild-to-moderate
Crohn's disease (CD) in children. METHODS: The consecutive, multicenter, open
label, non-comparative studies enrolled patients aged 6-17 years. In the
induction study, patients with active CD of the ileum and/or ascending colon
received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance
study, patients in remission received budesonide 6 mg once daily for 12 weeks.
The primary objective was assessment of safety, including glucocorticosteroid
related side effects and serum cortisol levels. Efficacy was assessed using the
Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of
life (HRQoL) using the IMPACT-III questionnaire. RESULTS: In the induction study
(n = 108), most adverse events were related to CD, commonly abdominal pain;
possible glucocorticosteroid-related effects included acne and increased appetite
but without significant weight gain. Subnormal morning cortisol levels were
observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity
from baseline (mean +/- standard deviation, 9.1 +/- 8.5 vs. 19.1 +/- 10.1, p <
.001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p <
.001). In the maintenance study (n = 50), mean disease activity worsened (p =
.047) with HRQoL unchanged (p = .33). CONCLUSIONS: Budesonide treatment was
generally well tolerated, although the potential for adrenal suppression was
noted. Budesonide was effective for induction of remission in children with mild
to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers:
NCT01444092, NCT01453946).
PMID- 28420281
TI - Long-term follow-up of antithrombotic management patterns in patients with acute
coronary syndrome in Russia: an observational study (EPICOR-RUS study).
AB - OBJECTIVE: This study sought to describe the short- and long-term (up to 2 years)
antithrombotic management patterns in a real-life setting for patients
hospitalized for an acute coronary syndrome (ACS) event, and to document clinical
outcomes. RESEARCH DESIGN AND METHODS: EPICOR-RUS was a multicenter (34 centers),
prospective, observational, longitudinal cohort study conducted across Russia on
antithrombotic management in hospitalized (within 24 hours of symptom onset) ACS
patients with 2 year follow-up. CLINICAL TRIAL REGISTRATION: NCT01373957.
RESULTS: A total of 600 ACS patients (71.1% male, mean age 60 years) were
enrolled; 599 were included for analysis. Diagnosis comprised STEMI (n = 375,
62.6%), NSTEMI (n = 147, 24.5%), and unstable angina (UA) (n = 77, 12.9%).
Percutaneous coronary intervention (PCI) was conducted in 64.3% of patients with
STEMI (with or without thrombolysis), 36.7% with NSTEMI, and 58.4% with UA. There
was undertreatment with dual antiplatelet therapy (DAPT) for STEMI, NSTEMI, and
UA: 14.7%, 25.9% and 16.9% of patients, respectively, were not receiving DAPT
during hospitalization, and 10.1%, 21.8% and 16.9% at discharge. Post-discharge,
of the STEMI group, only 72.4% of patients who were managed by PCI and 39.8% of
conservatively treated patients received DAPT at 12 months. The respective
figures in the NSTEMI group were 77.3% and 26.4%. In the STEMI cohort the
cumulative incidence of all-cause mortality was 3.2% at 1 year and 5.1% at 2
years of follow-up; in the NSTEMI cohort this was 2.7% and 4.8%, respectively.
There were no deaths by 12 months and one death by 24 months (1.3%) in the UA
population. CONCLUSION: Despite evidence-based guidelines for the management of
ACS, the real-world setting in Russia shows discrepancies in clinical practice,
highlighting the need for improvements for the optimal management of high-risk
patients with ACS.
PMID- 28420282
TI - Exploring predictors of treatment outcome in cognitive behavior therapy for sleep
disturbance following acquired brain injury.
AB - PURPOSE: To identify predictors of treatment response to cognitive behavior
therapy (CBT) for sleep disturbance following acquired brain injury (ABI).
METHODS: Classification and regression tree (CART) analysis was conducted on
individual patient data from two pilot randomized controlled trials (RCTs): one
in traumatic brain injury (TBI), the other in stroke. The combined sample
comprised 32 participants; 15 receiving CBT and 17 allocated to treatment as
usual (TAU). The outcome was reliable improvement on the Pittsburgh Sleep Quality
Index (PSQI). RESULTS: Study group was a statistically significant predictor of
outcome, with CBT participants more likely to achieve reliable improvements than
TAU (OR = 4.88, p = 0.042). Study group (CBT vs. TAU) exhibited an area under the
ROC curve (AUROC) of 69%. In separate CART analyzes, verbal memory (CVLT-II
>45.5), age (<47.5) and baseline depression (HADS-D > 6) predicted positive
outcomes in CBT recipients. Each of these variables added a small (~5%) but not
statistically significant amount to AUROC over study group. CONCLUSIONS: In this
ABI sample, better memory, younger age, and higher baseline depression were
associated with positive treatment response to CBT although individually these
variables were not better than group alone in predicting outcomes. The present
findings generate hypotheses for further investigation in future studies.
Implications for rehabilitation Cognitive behavior therapy improves sleep quality
over treatment as usual in persons with acquired brain injury. Individuals who
are younger in age with better memory and co-morbid symptoms of depression are
more likely to respond to the treatment. These findings are based on a small
sample and can be considered hypothesis generating for future clinical studies.
PMID- 28420283
TI - Design and characteristics of gellan gum beads for modified release of meloxicam.
AB - The aim of the presented work was to design, formulate and evaluate the
properties of low-acyl gellan macro beads with the potential application as
carriers for oral delivery of meloxicam (MLX) in the prophylaxis of colorectal
cancer. The beads were obtained by means of ionotropic gelation technique.
Calcium chloride (1.0%, 9.0 * 10-2 M) was used as the cross-linking agent. Nine
different polymer, drug and surfactant (Tween(r)80) mixtures were used for
production of the beads. The quantitative compositions of the mixtures were
generated with the application of the Design of Experiments (DoE) modulus from
the STATISTICA Software. The prepared formulations revealed 7.2-27.0% of drug
loading and 29.2-50.7% drug encapsulation efficiency. It turned out that 0.5%
amount of gellan gum in the mixtures was not sufficient to obtain spherical
beads. The morphology and surface of the dried beads were analyzed by SEM. Raman
spectra confirmed that MLX did not undergo structural changes during production
of the beads. The swelling behavior and degradation of the beads were evaluated
in three simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8). The
MLX in vitro release studies were conducted on USP apparatus IV, working in the
open loop mode. The obtained results showed that MLX release from the dried beads
was pH-dependent. The formulations obtained from mixtures containing 1.0 and 1.5%
of gellan may be considered as oral dosage forms for MLX, intended to omit the
stomach and release the drug in the distal parts of the gastrointestinal tract.
PMID- 28420284
TI - A systematic review of rehabilitation interventions to prevent and treat
depression in post-stroke aphasia.
AB - PURPOSE: Stepped psychological care is the delivery of routine assessment and
interventions for psychological problems, including depression. The aim of this
systematic review was to analyze and synthesize the evidence of rehabilitation
interventions to prevent and treat depression in post-stroke aphasia and adapt
the best evidence within a stepped psychological care framework. METHOD: Four
databases were systematically searched up to March 2017: Medline, CINAHL,
PsycINFO and The Cochrane Library. RESULTS: Forty-five studies met inclusion and
exclusion criteria. Level of evidence, methodological quality and results were
assessed. People with aphasia with mild depression may benefit from psychosocial
type treatments (based on 3 level ii studies with small to medium effect sizes).
For those without depression, mood may be enhanced through participation in a
range of interventions (based on 4 level ii studies; 1 level iii-3 study and 6
level iv studies). It is not clear which interventions may prevent depression in
post-stroke aphasia. No evidence was found for the treatment of moderate to
severe depression in post-stroke aphasia. CONCLUSIONS: This study found some
interventions that may improve depression outcomes for those with mild depression
or without depression in post-stroke aphasia. Future research is needed to
address methodological limitations and evaluate and support the translation of
stepped psychological care across the continuum. Implications for Rehabilitation
Stepped psychological care after stroke is a framework with levels 1 to 4 which
can be used to prevent and treat depression for people with aphasia. A range of
rehabilitation interventions may be beneficial to mood at level 1 for people
without clinically significant depression (e.g., goal setting and achievement,
psychosocial support, communication partner training and narrative therapy).
People with mild symptoms of depression may benefit from interventions at level 2
(e.g., behavioral therapy, psychosocial support and problem solving). People with
moderate to severe symptoms of depression require specialist mental
health/behavioral services in collaboration with stroke care at levels 3 and 4 of
stepped psychological care.
PMID- 28420285
TI - Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a
mucolytic agent for cystic fibrosis patients.
AB - OBJECTIVE: This study aimed to design and characterize an inhalable dry powder of
ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and
dornase alfa for the management of pulmonary infections in patients with cystic
fibrosis. METHODS: Ball milling, homogenization in isopropyl alcohol and spray
drying processes were used to prepare dry powders for inhalation. Physico
chemical characteristics of the dry powders were assessed via thermogravimetric
analysis, differential scanning calorimetry (DSC), Fourier transform infrared
spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The
particle size distribution, dissolution rate and permeability across Calu-3 cell
monolayers were analyzed. The aerodynamic parameters of dry powders were
determined using the Andersen cascade impactor (ACI). RESULTS: After the
micronization process, the particle sizes of the raw materials significantly
decreased. X-ray and DSC results indicated that although ciprofloxacin showed no
changes in its crystal structure, the structure of levofloxacin became amorphous
after the micronization process. FT-IR spectra exhibited the characteristic peaks
for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of
micro-homogenized and spray-dried ciprofloxacin were higher than that of
untreated ciprofloxacin. ACI results showed that all formulations had a mass
median aerodynamic diameter less than 5 MUm; however, levofloxacin microparticles
showed higher respirability than ciprofloxacin powders did. The permeability of
levofloxacin was higher than those of the ciprofloxacin formulations. CONCLUSION:
Together, our study showed that these methods could suitably characterize
antibiotic and mucolytic-containing dry powder inhalers.
PMID- 28420286
TI - Probing the Characteristics of Colour-Motion Binding and Its Dependence on
Persistent Surface Segregation.
AB - Identifying the spatial and temporal characteristics of visual feature binding is
a remaining challenge in the science of perception. Within the feature-binding
literature, disparate findings have suggested the existence of more than one
feature-binding mechanism with differing temporal resolutions. For example, one
surprising result is that temporal alternations between two different feature
pairings of colour and motion (e.g., orange dots moving left with blue dots
moving right) support accurate conjunction discrimination at alternation
frequencies of around 10 Hz and greater. However, at lower alternation
frequencies around 5 Hz, conjunction discrimination falls to chance. To further
investigate this effect, we present two experiments that probe the stimulus
characteristics that facilitate or impede feature binding. Using novel
manipulations of random dot kinematograms, we identify that facilitating surface
representations through temporal integration can enable accurate conjunction
discrimination at both intermediate and high alternation frequencies. We also
offer a neurally plausible evidence accumulator model to describe these results,
removing the need to suggest multiple binding mechanisms acting at different
timescales. In effect, we propose a single, flexible binding process, whereby the
relatively low temporal resolution for binding features can be circumvented by
extracting them from rapidly formed and persistent surface representations.
PMID- 28420287
TI - Associations between early caregiving and rural, low-SES, African-American
children's representations of attachment relationships.
AB - Little research has examined the legacy of early maternal care for later
attachment representations among low-income and ethnic minority school-aged
children. Using data from a sample of 276 rural, low-income, African-American
families, this study examined associations between maternal care in infancy and
children's representations of attachment figures in middle childhood. Maternal
care was coded from 10-min home-based observations at 6, 15, and 24 months of
age. Representations of attachment figures were assessed using the Manchester
Child Attachment Story Task at 6 years of age. Sensitive maternal care in infancy
was not significantly related to attachment security or episodic disorganized
behaviors in children's representations. However, children exposed to more harsh
intrusive parenting during infancy displayed less secure representations of
attachment figures in middle childhood and more episodic disorganized behaviors,
even after controlling for numerous child and family contextual covariates.
Findings inform conceptualizations of attachment formation among rural, low
income, African-American parent-child dyads.
PMID- 28420288
TI - Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the
antifungal sertaconazole: design, optimization and ex vivo evaluation.
AB - The purpose of the present study was to develop and optimize sertaconazole
microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin
retention of the drug. Following screening of various oils for maximum drug
solubility, 12 pseudoternary phase diagrams were constructed using oils
(Peceol(r), Capryol(r) 90), surfactants (Tween(r) 80, Cremophor(r) EL), a
cosurfactant (Transcutol(r) P) and water. A 21 * 31 * 21 * 31 full factorial
design was employed to optimize a ME of desirable characteristics. The MEs were
formulated by varying the oil type, oil concentration, surfactant type and
surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol(r), 55%
Tween(r) 80: Transcutol(r) (1:2), 40% water] and F31 [5% Peceol(r), 55%
Cremophor(r) EL: Transcutol(r) (1:2), 40% water] acquired mean droplet size of
75.21 and 8.68 nm, and zeta potential of 34.65 and 24.05 mV, respectively. Since
F22 showed higher STZ skin retention during ex vivo studies (686.47 MUg/cm2) than
F31 (338.11 MUg/cm2); hence it was incorporated in 0.5% Carbopol 934 gel to
augment STZ skin retention capability. STZ ME G exhibited higher STZ skin
retention (1086.1 MUg/cm2) than the marketed product "Dermofix(r) cream" (270.3
MUg/cm2). The antimycotic activity against C.albicans revealed increased zones of
inhibition for F22 and STZ ME G (35.75 and 30.5 mm, respectively) compared to
Dermofix(r) cream (26 mm). No histopathological changes were observed following
topical application of STZ ME G on rats' skin (n = 9). Overall, the obtained
results confirmed that the fabricated formulation could be a promising vehicle
for the dermal delivery of STZ.
PMID- 28420289
TI - Rhinoscleroma: a chronic infectious disease of poor areas with characteristic
histological features - report of a series of six cases.
AB - Rhinoscleroma is a chronic infectious disease that is endemic in certain poor
areas of the world. The diagnosis often relies on pathology, the outcome is
disappointing and then marked by recurrence. We present a retrospective series of
six patients histologically diagnosed with rhinoscleroma. Some clinical and
histological features of the disease are discussed below, as its adequate
management implies a multidisciplinary approach.
PMID- 28420290
TI - Peripheral blood smear: beyond routine morphology.
PMID- 28420291
TI - A study of long-term stability and antimicrobial activity of chlorhexidine,
polyhexamethylene biguanide, and silver nanoparticle incorporated in sericin
based wound dressing.
AB - In this study, three kinds of antiseptics which were 0.05% chlorhexidine, 0.2%
polyhexamethylene biguanide (PHMB), or 200 ppm silver nanoparticle was introduced
to incorporate in the sericin-based scaffold to produce the antimicrobial
dressing for the treatment of infected chronic wound. The effects of antiseptic
incorporation on the stability, release of sericin, and short-term and long-term
(6 months) antimicrobial activity of the sericin dressing against gram-negative
and gram-positive bacteria were investigated. We showed that the incorporation of
each antiseptic did not have significant effect on the internal morphology (pore
size ~ 73-105 MUm), elasticity (Young's modulus ~ 200-500 kPa), and the sericin
release behavior of the sericin-based dressing. The release of sericin from the
dressing was prolonged over 120 h and thereafter. Comparing among three
antiseptics, 0.05% chlorhexidine incorporated in the sericin dressing showed the
highest immediate and long-term (6 months) antimicrobial effect (largest
inhibition zone) against most bacteria either gram-positive or gram-negative
bacteria. The in vivo safety test following ISO10993 standard (Biological
evaluation of medical devices - Part 6: Tests for local effects after
implantation) confirmed that the sericin dressing incorporating 0.05%
chlorhexidine did not irritate to tissue, comparing with the commercial material
used generally in clinic (Allevyn(r), Smith & Nephew). We suggested the sericin
dressing incorporating 0.05% chlorhexidine for the treatment of infected chronic
wound. Chlorhexidine would reduce the risk of infection while the sericin may
promote wound healing.
PMID- 28420292
TI - Neuroendocrine tumor of cecum in patient treated with imatinib mesylate for
blastic phase of chronic myeloid leukemia.
AB - Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice
in patients with chronic myeloid leukemia (CML). It is considered a very safe
drug, with mostly mild and reversible side effects. Lately, it has been suggested
that adverse events may occur after a long term. We report a case of a 72-year
old woman diagnosed with blastic phase of Philadelphia chromosome positive CML
treated with IM for 28 months. The patient presented first with ascites as a side
effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine
tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of
a NET as a secondary malignancy (SM) after IM treatment. SM have been described
in patients on IM before. It is unclear whether these tumors are caused by
imatinib or found more easily because of close follow-up.
PMID- 28420293
TI - Acute gastric outlet obstruction secondary to exclusive paraoesophageal small
bowel herniation: a case report.
AB - INTRODUCTION: Herniation of abdominal viscera into the thorax may occur as a
consequence of abnormal defects in the diaphragm. In adults, the most common
condition relates to herniations through a weakened crural orifice via which the
oesophagus normally traverses. These hiatus hernias are classified as types I-IV
depending on the extent of visceral involvement. CASE REPORT: We present here a
case of type IV hiatus hernia with massive mediastinal herniation of the small
bowel, yet remarkable in that the stomach itself remained completely intra
abdominal. Gastric outlet obstruction occurred as a consequence of extrinsic
proximal small bowel compression. DISCUSSION: To our knowledge this is the first
reported case of paraoesophageal hernia exclusively involving small bowel,
without involving any part of the stomach, and yet causing gastric outlet
obstruction.
PMID- 28420294
TI - SMART - Recognising the value of existing practice and introducing recent
developments: leaving no stone unturned in the assessment and treatment of the
PDOC patient.
AB - Over the last 25 years there have been a number of papers highlighting the issues
of high rates of misdiagnosis in prolonged disorders of consciousness (PDOC)
(Andrews, K., Murphy, L., Munday, R., & Littlewood, C. (1996). Misdiagnosis of
the vegetative state: Retrospective study in a rehabilitation unit. BMJ,
313(7048), 13-16; Childs, N. L., Mercer, W. N., & Childs, H. W. (1993). Accuracy
of diagnosis of persistent vegetative state. Neurology, 43(8), 1465-1467).
Surprisingly, these rates still remain at the same level despite defined criteria
for diagnosis (Schnakers, C., Vanhaudenhuyse, A., Giacino, J., Ventura, M., Boly,
M., Majerus, S.,...Laureys, S. (2009). Diagnostic accuracy of the vegetative and
minimally conscious state: Clinical consensus versus standardized neurobehavioral
assessment. BMC Neurology, 9(35), 1-5; Van Erp, W., Larvrijsen, J., Vos, P., Bor,
H., Laureys, S., & Koopmans, R. (2015). The vegetative state: Prevalence,
misdiagnosis and treatment limitations. JAMDA, 85, e9-85.e14. doi:
10.1016/j.jamda.2014.10.014 ). This indicates the continued need for careful
standardised assessment by skilled assessors to identify all potential meaningful
responses and to establish a correct and incontrovertible diagnosis. The Sensory
Modality Assessment and Rehabilitation Technique (SMART) is one of three
assessments identified for the assessment of PDOC in the Royal College of
Physician guidelines (Royal College of Physicians, 2013). The RCP guidelines and
recent publications have highlighted and substantiated the value of some of the
existing practices and unique features of the SMART. In recognition of the need
to keep SMART current, SMART Version 3 is being developed and will be launched
shortly. The interim SMART developments will be introduced in this paper and
applied to practice through the illustration of a case study. Evidence suggests
that SMART is a current and invaluable tool for the clinical and medico-legal
assessment and treatment of the PDOC patient.
PMID- 28420295
TI - Optimization of methotrexate loaded niosomes by Box-Behnken design: an
understanding of solvent effect and formulation variability.
AB - Dermal drug delivery system which localizes methotrexate (MTX) in the skin is
advantageous in topical treatment of psoriasis. The aim of the current study was
to understand dilution effects and formulation variability for the potential
formation of niosomes from proniosome gels of MTX. Box-Behnken's design was
employed to prepare a series of MTX proniosome gels of Span 40, cholesterol (Chol
X1) and Tween 20 (T20-X2). Short chain alcohols (X3), namely ethanol (Et),
propylene glycol (Pg) and glycerol (G) were evaluated for their dilution effects
on proniosomes. The responses investigated were niosomal vesicles size (Y1), MTX
entrapment efficiency percent (EE%-Y2) and zeta potential (Y3). MTX loaded
niosomes were formed immediately upon hydration of the proniosome gels with the
employed solvents. Addition of Pg resulted in a decrease of vesicular size from
534 nm to 420 nm as Chol percentage increased from 10% to 30%, respectively. In
addition, increasing the hydrophilicity of the employed solvents was enhancing
the resultant zeta potential. On the other hand, using Et in proniosomal gels
would abolish Chol action to increase the zeta potential value and hence less
stable niosomal dispersion was formed. The optimized formula of MTX loaded
niosomes showed vesicle size of 480 nm, high EE% (55%) and zeta potential of
25.5 mV, at Chol and T20 concentrations of 30% and 23.6%, respectively, when G
was employed as the solvent. Hence, G was the solvent of choice to prepare MTX
proniosomal gels with a maintained stability and highest entrapment.
PMID- 28420296
TI - The effect of engineered nanotopography of electrospun microfibers on fiber
rigidity and macrophage cytokine production.
AB - Currently, it is unknown how the mechanical properties of electrospun fibers, and
the presentation of surface nanotopography influence macrophage gene expression
and protein production. By further elucidating how specific fiber properties
(mechanical properties or surface properties) alter macrophage behavior, it may
be possible to create electrospun fiber scaffolds capable of initiating unique
cellular and tissue responses. In this study, we determined the elastic modulus
and rigidity of fibers with varying topographies created by finely controlling
humidity and including a non-solvent during electrospinning. In total,five fiber
scaffold types were produced. Analysis of fiber physical properties demonstrated
no change in fiber diameter amongst the five different fiber groups. However, the
four different fibrous scaffolds with nanopits or divots each possessed different
numbers of pits with different nanoscale dimensions. Unpolarized bone marrow
derived murine macrophages (M0), macrophages polarized towards a pro-inflammatory
phenotype (M1), or macrophages polarized towards anti-inflammatory phenotype
(M2b) were placed onto each of the scaffolds and cytokine RNA expression and
protein production were analyzed. Specific nanotopographies did not appreciably
alter cytokine production from undifferentiated macrophages (M0) or anti
inflammatory macrophages (M2b), but a specific fiber (with many small pits) did
increase IL-12 transcript and IL-12 protein production compared to fibers with
small divots. When analyzing the mechanical properties between fibers with divots
or with many small pits,divoted fibers possessed similar elastic moduli but
different stiffness values. In total,we present techniques capable of creating
unique electrospun fibers. These unique fibers have varying fiber mechanical
characteristics and modestly modulate macrophage cytokine expression.
PMID- 28420297
TI - The social trajectory of brain tumor: a qualitative metasynthesis.
AB - PURPOSE: Research indicates that strong social ties can buffer the adverse
effects of chronic illness on psychological well-being. Brain tumor typically
leads to serious functional impairments that affect relationships and reduce
social participation. This metasynthesis aimed to identify, appraise and
integrate the findings of qualitative studies that reveal the impact of brain
tumor on social networks. METHODS: Four major databases (PubMed, CINAHL, Cochrane
Library and PsycINFO) were systematically searched from inception to September
2016 for qualitative studies that reported findings on the impact of primary
brain tumor on social networks during adulthood. Twenty-one eligible studies were
identified and appraised according to the Consolidated Criteria for Reporting
Qualitative Research. Key findings of these studies were integrated to form
superordinate themes. RESULTS: The metasynthesis revealed the core themes of: 1)
Life disrupted; 2) Navigating the new reality of life; and 3) Social survivorship
versus separation. CONCLUSIONS: Multiple changes typically occur across the
social trajectory of brain tumor, including a loss of pre-illness networks and
the emergence of new ones. Understanding the barriers and facilitators for
maintaining social connection may guide interventions for strengthening social
networks and enhancing well-being in the context of brain tumor. Implications for
rehabilitation Social networks and roles are disrupted throughout the entire
trajectory of living with brain tumor Physical, cognitive and psychological
factors represent barriers to social integration Barriers to social integration
may be addressed by supportive care interventions Compensatory strategies,
adjusting goals and expectations, educating friends and family and accepting
support from others facilitate social reintegration throughout the trajectory of
living with brain tumor.
PMID- 28420298
TI - Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral
therapy or receiving a first-line treatment.
AB - BACKGROUND: The combination antiretroviral therapy (cART) has dramatically
improved the life expectancy of patients with HIV infection, but may lead to
several long-term metabolic abnormalities. However, data about the frequency of
metabolic syndrome (MS) in HIV-infected people vary considerably across different
observational studies. METHODS: The prevalence of MS among HIV-infected patients
was evaluated by a cross-sectional study conducted among subjects naive to cART
or receiving the first antiretroviral regimen and referring to our Clinics from
January 2015 to December 2015. The diagnosis of MS was made based on the National
Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and
International Diabetes Federation (IDF) criteria. RESULTS: The study recruited
586 patients: 98 naive to cART and 488 under the first antiretroviral treatment.
The prevalence of MS, according to NCEP-ATP III criteria, was significantly
higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014).
The most frequently reported components of MS among treated patients were high
triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and
hypertension (19.7%). On multivariate analysis, long duration of HIV infection,
low nadir of CD4 lymphocytes, high body mass index, current use of one protease
inhibitor, and long duration of cART were significantly associated with a higher
risk of MS, while current use of one integrase inhibitor was significantly
associated with a lower risk of MS. CONCLUSIONS: The non-negligible prevalence of
MS among HIV-infected patients under cART requires a careful and periodic
monitoring of its components, with particular attention to dyslipidemia and
hypertension.
PMID- 28420299
TI - Surface chemistry of gold nanoparticles determines the biocorona composition
impacting cellular uptake, toxicity and gene expression profiles in human
endothelial cells.
AB - This study investigated the role of nanoparticle size and surface chemistry on
biocorona composition and its effect on uptake, toxicity and cellular responses
in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold
nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and
polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona
proteins among the various AuNP, revealing largely surface chemistry-dependent
signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size
distribution analysis revealed the relative instability and aggregation inducing
potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular
dichroism analysis showed surface chemistry-dependent conformational changes of
proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and
HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC
formation. Cell viability studies demonstrated dose-dependent toxicity of BPEI
AuNP. Transcriptional profiling studies revealed 126 genes, from 13 biological
pathways, to be differentially regulated by 40 nm bare and PC-bound BPEI-AuNP (PC
BPEI-AuNP). Furthermore, PC formation relieved the toxicity of cationic BPEI-AuNP
by modulating expression of genes involved in DNA damage and repair, heat shock
response, mitochondrial energy metabolism, oxidative stress and antioxidant
response, and ER stress and unfolded protein response cascades, which were
aberrantly expressed in bare BPEI-AuNP-treated cells. NP surface chemistry is
shown to play the dominant role over size in determining the biocorona
composition, which in turn modulates cell uptake, and biological responses,
consequently defining the potential safety and efficacy of nanoformulations.
PMID- 28420300
TI - Epinephrine-induced pulmonary edema during hip arthroscopy: a report of two cases
and a review of the literature.
AB - OBJECTIVES: Hip arthroscopy utilization has significantly increased in recent
years. While it is a relatively safe procedure, it is not without risk. Life
threatening complications, albeit rare, can potentially occur and must be
appropriately recognized and treated. We describe 2 cases in which patients'
undergoing hip arthroscopy developed pulmonary edema and their respective courses
of treatment. METHODS: Both patients were being treated for symptomatic
femoroacetabular impingement (FAI), with labral tears, requiring operative
management after a failed trial of conservative management. The complication
occurred during a primary hip arthroscopy procedure and a retrospective review of
their clinical records and intra-operative notes was performed. RESULTS: Hip
arthroscopy was performed under spinal anesthetic in the supine position in both
patients. In both procedures, patients developed severe hypertension and
tachycardia, with subsequent oxygen desaturations with noted pulmonary edema. The
postulated etiology was systemic effects from intra-articular epinephrine,
causing acute pulmonary edema with corresponding cardiovascular changes. With
supportive ventilation, selective alpha-adrenergic blocker and furosemide
administration, and cessation of epinephrine exposure, vital signs normalized and
both patients experienced symptom resolution. CONCLUSION: During arthroscopy, if
acute hypertension, tachycardia and hypoxia develop, epinephrine-induced
pulmonary edema should be considered as a cause by the treating orthopedic
surgeon and anesthesiologist in order to initiate an appropriate treatment plan.
PMID- 28420301
TI - Seizures in Pediatric Patients With Liver Transplant and Efficacy of
Levetiracetam.
AB - The aim of this study was to evaluate the risk factors, clinical implications,
and prognosis of new-onset seizures that occurred after pediatric liver
transplantation, and to assess the efficacy of levetiracetam treatment. The
clinical and laboratory data of liver transplanted 28 children who had seizures
after liver transplantation and specifically of 18 children who received
levetiracetam were analyzed retrospectively. Sixteen patients (88.9%) remained
seizure-free and in 2 (11.1%), more than 50% reduction in seizures were detected
with levetiracetam treatment. In conclusion, seizures are generally the most
common complication by a spectrum of seizure types, and sometimes cause
symptomatic epilepsy. The most common risk factors for seizures in transplant
recipients is immunosuppressant toxicity. Currently, there isn't a specific
treatment involving the transplant patient population. Levetiracetam may be
preferable in pediatric patients as it's reliable for liver disease and has
advantages in the treatment of postoperative seizures due to its intravenous
usage.
PMID- 28420302
TI - The Genus Spirorchis MacCallum, 1918 (Digenea: Schistosomatoidea) and the Early
History of Parasitology in the United States.
AB - We know little about the founders of our discipline apart from their scientific
contributions and brief biographical sketches, most frequently in published
obituaries. A number of years ago, Ralph Lichtenfels, then Director of the
National Parasite Collection, sent me photocopies of letters between Henry
Baldwin Ward, Horace W. Stunkard, George A. MacCallum, and William G. MacCallum
dating from the early years of the 20th century that hinted at a series of
conflicts centered on the proposal of Spirorchis MacCallum, 1918 (Digenea:
Schistosomatoidea). The description of a fluke that matured in the blood of a
tetrapod and that was morphologically similar to the schistosomes of humans was
in its time a transformative discovery; and the scientist who published it would
have garnered some scholarly recognition. Herein, I provide an historical account
of the issues and the motives of each individual and the eventual resolution of
these matters.
PMID- 28420303
TI - Juvenile Papillomatosis (Swiss-Cheese Disease) of Breast in an Adult Male With
Sequential Diagnoses of Ipsilateral Intraductal, Invasive, and Widely Metastatic
Carcinoma: A Case Report and Review of the Disease in Males.
AB - Juvenile papillomatosis of the breast (JPB, also known as Swiss cheese disease)
is a rare ailment that typically afflicts young females, and presents as a mass
forming lesion. The lesional mass usually comprises multiple cysts and duct
stasis, amid a variety of proliferative and nonproliferative epithelial changes.
The proliferative changes include papillary hyperplasia, florid hyperplasia, and
papillary apocrine hyperplasia. Concurrent carcinoma (either in situ or invasive)
is present in approximately 10% of cases at presentation, and subsequent
carcinoma (either in situ or invasive) is diagnosed in about 10% of patients.
About 20% of patients have a strong family history of breast carcinoma. A total
of 10 cases of JPB have been previously reported in males, both children and
adults, only one of which, in a 33-year-old, was associated with invasive
carcinoma. Here, another case of JPB in a 45-year-old male-one with subsequent
sequential diagnoses of ipsilateral intraductal carcinoma, invasive carcinoma,
and widely metastatic carcinoma over the course of 15 years-is reported.
PMID- 28420304
TI - Ectopic Pacinian Corpuscle in the Prostate.
PMID- 28420305
TI - Dual Pathology: Double Trouble in a Colonic Biopsy.
PMID- 28420306
TI - Diffuse Large B-Cell Lymphoma in a Patient With Necrotizing Fasciitis Secondary
to Silicone Biopolymer Implants in Buttock.
PMID- 28420307
TI - Adapting the revised prenatal coping inventory (NuPCI) for use in a Spanish
population.
AB - OBJECTIVE: To adapt the Revised Prenatal Coping Inventory (NuPCI) for the
evaluation of prenatal stress coping strategies utilised by Spanish women.
METHODS: A cross-sectional study was performed to evaluate the psychometric
properties of NuPCI adapted for a Spanish population. Two hundred and sixty one
puerperium women completed the NuPCI at the time of discharge after childbirth.
Instrument construct validity was evaluated using subscale item correlations.
Internal consistency was assessed using Cronbach's alpha test. RESULTS: Items
from each subscale (Preparation, Avoidance and Spiritual - Positive Coping) were
significantly correlated with the global result (p < .001). The internal
reliability of the NuPCI demonstrated suitable values for each of the three
coping strategies (alpha > 0.7). The most frequently used coping strategy was
Preparation and the least used was Avoidance. Utilisation of the coping
strategies with Preparation decreased with increasing parity (p = .002) and
greater prenatal stress was associated with increased use of the Avoidance coping
strategy (p < .001). CONCLUSIONS: The NuPCI adapted for Spanish women
demonstrates good psychometric properties for evaluating the three types of
prenatal stress coping strategies: Preparation, Avoidance and Spiritual -
Positive Coping. Results were similar to those presented by the instrument in its
English language version.
PMID- 28420308
TI - Nanodispersion-loaded mucoadhesive polymeric inserts for prolonged treatment of
post-operative ocular inflammation.
AB - Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded
nanodispersion aiming the sustained delivery of the drug to the cornea have been
developed and characterised for the treatment of post-operative ocular
inflammation. Nanodispersions were prepared by ionic gelation method with various
concentrations of chitosan and sodium tripolyphosphate. The developed
nanodispersions were analysed for morphology, particle size, dispersion
homogeneity, zeta potential, entrapment efficiency and drug release. The
nanodispersion that showed the smallest particle size and the highest entrapment
efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m
films. The formulation with optimum physicomechanical properties was selected to
study its ex vivo transcorneal permeation through freshly excised bovine cornea
in comparison with the nanodispersion and the marketed eye drops (Acular(r)). The
polymeric ocular film showed greater permeation than aqueous eye drops. Moreover,
the ocular film revealed a prolonged anti-inflammatory effect compared to eye
drops when applied to inflamed rabbit's eyes.
PMID- 28420310
TI - Helminth Fauna Associated with Three Neotropical Bat Species (Chiroptera:
Mormoopidae) in Veracruz, Mexico.
AB - Bats are recognized as potential hosts of pathogens exploiting the food chain to
reach them as definitive hosts. However, very little is known about their
endoparasites, especially for Neotropical bats. In this study, we assessed the
helminth fauna associated with 3 insectivorous bat species roosting in the same
single hot cave in central Veracruz, Mexico: Mormoops megalophylla, Pteronotus
davyi, and Pteronotus personatus. During a period of 1 yr (April 2007-2008), 135
mormoopid bats in total were collected and examined for helminths. Six parasite
species representing 3 types of intestinal helminths were found: 1 cestode
Vampirolepis elongatus; 2 trematodes Maxbraunium tubiporum and Ochoterenatrema
labda; and 3 nematodes Linustrongylus pteronoti, Molineidae gen. sp., and
Capillaria sp. Overall, trematodes were the most abundant parasite group (72.4%),
followed by nematodes (20.7%) and cestodes (6.9%). Species-accumulation curves
suggest that the worms collected (n = 1,331) from these 6 parasite species
comprise the helminth fauna associated with the 3 bat populations studied. The
only species shared by the 3 bat species was Capillaria sp. Most (5/6) of the
helminth species recorded use Lepidoptera and Diptera as intermediate hosts;
therefore, diet is likely the main source of infection. Although insectivorous
bats are considered dietary generalist species, the differences found in helminth
diversity in these sympatric populations of closely related bat species, suggest
that diet partitioning occurs in mormoopid bat communities. Helminths tend to
exploit the food chain to reach their final hosts; therefore, studying these
parasites can provide useful information to further understand the biology of
bats.
PMID- 28420309
TI - A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using
a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior
Cingulate Cortex and the Left Cerebellum.
AB - The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We
used proton magnetic resonance spectroscopy to investigate metabolite
concentration ratios in the anterior cingulate cortex and left cerebellum in ASD.
In the ACC and left cerebellum studies, the ASD group and intelligence quotient-
and age-matched control group consisted of 112 and 114 subjects and 65 and 45
subjects, respectively. In the ASD group, gamma-aminobutyric acid (GABA)+/
creatine/phosphocreatine (Cr) was significantly decreased in the anterior
cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr
was significantly decreased in the left cerebellum compared to those in the
control group. In addition, both groups showed negative correlations between
Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between
GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have
hypoGABAergic alterations in the anterior cingulate cortex and
hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.
PMID- 28420311
TI - Exploring the effect of formulation parameters on the particle size of
carboxymethyl chitosan nanoparticles prepared via reverse micellar crosslinking.
AB - Carboxymethyl chitosan (CMCh), as a non-toxic, biocompatible and biodegradable
semi-synthetic biopolymer with mucoadhesive properties, is widely investigated
for targeting drug or gene delivery applications. Here, fabrication of CMCh
nanoparticles will be reported using a reverse (w/o) micellar system to provide
particles with tuneable mean sizes. Reverse microemulsions were prepared by
dispersing aqueous solution of CMCh in n-hexane using sodium-bis(ethylhexyl)
sulfosuccinate (AOT) and glutaraldehyde (GA) as an emulsifier and a crosslinking
agent, respectively. The obtained particles were perfectly spherical in the
nanometric size range (40-140 nm) with a narrow size distribution according to
the FE-SEM images. To determine the effective parameters on the mean nanosphere
size, CMCh, AOT and GA concentrations were varied according to a full-factorial,
three-level design-of-experiments. After evaluating the results, it was found
that AOT and CMCh concentrations had a significant effect on the mean nanosphere
size while GA concentration surprisingly showed non-significant, minor effects on
the same response.
PMID- 28420312
TI - Delivering E-lectures effectively and efficiently using Google DriveTM.
PMID- 28420315
TI - Dental care attendance and refrainment from dental care among adults.
AB - OBJECTIVE: The aim of this study was to analyse dental care utilization,
refrainment from self-perceived needed dental care and the association with
socioeconomic indicators among adult individuals. MATERIALS AND METHODS: This
cross-sectional survey included 3500 randomly selected adult individuals.
Telephone interviews were conducted and the participants answered a battery of
questions regarding dental visiting habits, health, socioeconomic position (SEP),
behavioural factors and lifestyle indicators. RESULTS: The outcome 'dental
visits' was significantly correlated with SEP, especially with monetary
dimensions, such as income and economic resources for unforeseen expenditures.
However, educational level was not a significant predictor in the tested
statistical models. Furthermore, other covariates that contributed significantly
to the models were ethnicity, dental anxiety and lifestyle factors, albeit with a
different pattern of impact on the two outcome dimensions. Important features of
the SEP variables were the stepwise gradient relative to the outcomes,
implicating that the lower the SEP status, the greater the risk of reporting
irregular dental visiting habits and refraining from dental care due to financial
problems. CONCLUSIONS: Dental care utilization and refraining from dental care
for financial reasons clearly reveal associations with socioeconomic positions
among adult individuals.
PMID- 28420316
TI - Persistence of secondary prevention medication and related factors for acute
ischemic stroke and transient ischemic attack in China.
AB - OBJECTIVE: We recently measured the longitudinal use of secondary prevention
medication following hospital discharge and the factors influencing persistence
in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA)
in China. METHODS: Patients with AIS and TIA who were enrolled in the China
National Stroke Registry II from June 2012 to January 2013 were surveyed to
determine persistence. The medications included antiplatelet therapies, warfarin,
antihypertensive therapies, statins, and diabetes medications. We determined
persistence for a three-month period following discharge. Persistence was defined
as the continuation of all secondary preventive medications prescribed upon
hospital discharge. The factors associated with medication persistence 3 months
after discharge were examined using a multivariable logistic regression. RESULTS:
Of the 21,592 patients with AIS and TIA, 18,344 (91.2%) were eligible for
analysis. After 3 months post-discharge, 46.2% of the subjects continued to take
all secondary prevention medications prescribed at discharge. Independent
predictors of three-month medication persistence included younger age, absence of
a history of diabetes or atrial fibrillation, higher family income, less severe
stroke, index cerebrovascular event of ischemic stroke, and being treated in a
hospital with a stroke unit and more beds in the neurology department.
CONCLUSIONS: More than half of patients with AIS and TIA reported discontinuing
one or more secondary prevention medications within 3 months of hospital
discharge. Several factors associated with medication persistence were
identified. Here, we propose strategies that could be implemented to improve the
quality of secondary prevention.
PMID- 28420317
TI - The role of coherence of mind and reflective functioning in understanding binge
eating disorder and co-morbid overweight.
AB - Coherence of mind and reflective functioning may impact negative affect and
interpersonal functioning over and above the effects of symptoms of depression
and interpersonal problems that contribute to symptoms of binge-eating disorder
(BED) and overweight/obesity. Matched samples of overweight women with BED and
overweight and normal weight women without BED completed the Adult Attachment
Interview, a measure of depressive symptoms, and a measure of interpersonal
problems. Greater symptoms of depression distinguished women with BED from the
matched comparison samples. Greater interpersonal problems differentiated women
with BED from overweight women without BED. Coherence of Mind scores did not
differentiate the samples. However, lower Reflective Functioning scores did
distinguish both women with BED and overweight women without BED from normal
weight women. Lower reflective functioning may lead to binge eating independent
of depressive symptoms and interpersonal problems.
PMID- 28420318
TI - Advancing Clinicopathologic Diagnosis of High-risk Neuroblastoma Using
Computerized Image Analysis and Proteomic Profiling.
AB - A subset of patients with neuroblastoma are at extremely high risk for treatment
failure, though they are not identifiable at diagnosis and therefore have the
highest mortality with conventional treatment approaches. Despite tremendous
understanding of clinical and biological features that correlate with prognosis,
neuroblastoma at ultra-high risk for treatment failure remains a diagnostic
challenge. As a first step towards improving prognostic risk stratification
within the high-risk group of patients, we determined the feasibility of using
computerized image analysis and proteomic profiling on single slides from
diagnostic tissue specimens. After expert pathologist review of tumor sections to
ensure quality and representative material input, we evaluated multiple regions
of single slides as well as multiple sections from different patients' tumors
using computational histologic analysis and semiquantitative proteomic profiling.
We found that both approaches determined that intertumor heterogeneity was
greater than intratumor heterogeneity. Unbiased clustering of samples was
greatest within a tumor, suggesting a single section can be representative of the
tumor as a whole. There is expected heterogeneity between tumor samples from
different individuals with a high degree of similarity among specimens derived
from the same patient. Both techniques are novel to supplement pathologist review
of neuroblastoma for refined risk stratification, particularly since we
demonstrate these results using only a single slide derived from what is usually
a scarce tissue resource. Due to limitations of traditional approaches for
upfront stratification, integration of new modalities with data derived from one
section of tumor hold promise as tools to improve outcomes.
PMID- 28420319
TI - BCOR-CCNB3 Undifferentiated Sarcoma-Does Immunohistochemistry Help in the
Identification?
AB - Recent methodology has enabled the identification of some new genetic subgroups
within the melting pot of lesions presently classified by the 2013 WHO
classification as "undifferentiated/unclassified sarcomas". One of these
subgroups is characterized by a paracentric inversion of the X chromosome with
consequent formation of a BCOR-CCNB3 fusion. Clinical and pathological features
of these tumors overlap with the Ewing sarcoma family as well as other soft
tissue sarcomas, thus making them difficult to diagnose. To investigate the
morphological and immunohistochemical characteristics of BCOR-CCNB3 positive
sarcoma, we reviewed two sarcoma series, comprising 632 and 121 cases. The 11
tumors harboring the BCOR-CCNB3 fusion, identified by CCNB3 immunohistochemistry
and/or RT-PCR, were reevaluated for morphological characteristics and further
immunohistochemical investigations for CCNB3, SATB2, and Pax8 were performed.
Tumors harboring a BCOR-CCNB3 fusion (11/753) occured exclusively in males, with
a mean age at diagnosis of 12.9 years, and were mainly axially located. In this
group of either spindled or round cell tumors, vesicular nuclei with finely
dispersed chromatin, inconspicuous nucleoli and an arciform vascular pattern were
pathognomonic. More than 50% of cases stained positive for SATB2 and Pax8,
raising the hypothesis of a potential use of these markers in the identification
of BCOR-CCNB3 positive undifferentiated/unclassified sarcomas. CCNB3 was
confirmed as a useful ancillary immunohistochemical marker.
PMID- 28420320
TI - Pediatric Non-vestibular Schwannoma.
AB - While the clinicopathologic features of pediatric vestibular schwannomas, often
in the context of neurofibromatosis type 2 (NF2), have been well studied, there
is less data regarding the characteristics of pediatric non-vestibular
schwannomas (NVS). Additionally, the rate of loss of SMARCB1/INI1 expression in
this population has not been systematically evaluated. Our institutional archives
were searched for cases of NVS arising in patients 18 years or younger.
Clinicopathologic features including SMARCB1/INI1 status were assessed for each
case. Twenty-three NVS from 9 males and 13 females (age range, 2 months to 18
years) were identified, and sites included paraspinal (n = 10), head and neck (n
= 6), extremities (n = 4), trunk (n = 1), mediastinum (n = 1), and
retroperitoneum (n = 1); 22 cases were Antoni A predominant with 6 cases
comprising solely Antoni A tissue. The mitotic rate of the tumors ranged from 0
to 10/10 high-power fields (HPFs), and 3 tumors had mitotic rates of >=4
mitoses/10 HPFs. Two tumors showed plexiform architecture. No NVS showed diffuse
atypia, calcifications, microcystic/reticular architecture, epithelioid
morphology, pseudoglandular change, neuroblastoma-like features, or necrosis. All
tumors tested (23/23) showed retained nuclear expression of SMARCB1/INI1. Follow
up was available in 21 patients (range 1 week to 194 months), and 5 tumors
recurred. Pediatric NVS have a relatively homogeneous appearance with a
predominance of Antoni A areas. Pathologists should be aware that schwannomas in
this age group may be cellular with mitotic rates of >=4/10 HPFs to avoid
misclassification as a spindle cell sarcoma.
PMID- 28420321
TI - Submucosal Colonic Lipoblastoma Presenting With Colo-colonic Intussusception in
an Infant.
AB - Lipoblastoma is a benign adipose tumor typically presenting in infancy in
superficial soft tissues of extremities. Intestinal complications secondary to
intraabdominal or retroperitoneal involvement are exceedingly rare. We describe a
unique case of a primary intestinal lipoblastoma arising from the submucosa of
the transverse colon in an otherwise healthy 18-month-old boy. He presented with
a history of reducible rectal prolapse, rectal bleeding, and episodic abdominal
pain and was initially treated for constipation. Imaging identified a short colo
colonic intussusception, confirmed at laparotomy, and a fatty mass thought to
arise from the mesentery. Pathological examination of the resected transverse
colon revealed a submucosal tumor composed of a mixture of mature adipose tissue,
foci of myxoid mesenchymal tissue with desmin positive, HMGA2 negative spindle
cells, and scattered lipoblasts, characteristic of lipoblastoma. Lipoblastoma
should be considered as a potential albeit rare cause of intussusception in young
children, where a pathologic lead point is infrequently identified.
PMID- 28420322
TI - Epidemiology of paediatric renal stone disease: a 22-year single centre
experience in the UK.
AB - BACKGROUND: Whilst still rare, the incidence of paediatric stone disease is
increasing in developed countries and it is important to evaluate the aetiology.
We set up a dedicated renal stone service for children combining medical and
surgical expertise in 1993 and now have a large case series of children to
investigate the epidemiology. METHODS: A retrospective hospital note review of
children presenting with kidney stones during the last 22 years (1993-2015) was
conducted. All patients had a comprehensive infective and metabolic screen and
were classified as metabolic, infective or idiopathic stone disease. RESULTS:
Five hundred eleven patients (322 male) were reviewed. The median age of
presentation was 4.4y for males (1 m-16.6y) and 7.3y (1-18.5y) for females with a
median height and weight on the 25th centile for male and on 10th and 25th for
female, respectively. One hundred seventy five (34%) had an underlying metabolic
abnormality, 112 (22%) had infective stones and 224 (44%) were classified as
idiopathic. Of the 175 patients with a metabolic abnormality: 91 (52%) had
hypercalciuria (76 persistent and 15 transient), 37 (21%) hyperoxaluria, 38 (22%)
cystinuria, 3 (2%) abnormalities in the purine metabolism and the remainder other
metabolic abnormalities. Bilateral stones occurred in 27% of the metabolic group
compared to 16% in the non-metabolic group (OR 0.2, p < 0.05). Urinary tract
infection was a common complication (27%) in the metabolic group. CONCLUSIONS: In
this paper, we present the largest cohort of paediatric stone disease reported
from a developed country giving details on both, clinical and laboratory data. We
show that in the majority of the patients there is an identifiable underlying
metabolic and/or infective aetiology emphasizing the importance of a full work up
to provide adequate treatment and prevent recurrence. Moreover, we show that
stone disease in children, in contrast to the adult population, does not seem to
be associated with obesity, as children have a weight below average at
presentation.
PMID- 28420324
TI - Evaluation of a technology-enhanced integrated care model for frail older
persons: protocol of the SPEC study, a stepped-wedge cluster randomized trial in
nursing homes.
AB - BACKGROUND: Limited evidence exists on the effectiveness of the chronic care
model for people with multimorbidity. This study aims to evaluate the
effectiveness of an information and communication technology- (ICT-)enhanced
integrated care model, called Systems for Person-centered Elder Care (SPEC), for
frail older adults at nursing homes. METHODS/DESIGN: SPEC is a prospective
stepped-wedge cluster randomized trial conducted at 10 nursing homes in South
Korea. Residents aged 65 or older meeting the inclusion/exclusion criteria in all
the homes are eligible to participate. The multifaceted SPEC intervention, a
geriatric care model guided by the chronic care model, consists of five
components: comprehensive geriatric assessment for need/risk profiling,
individual need-based care planning, interdisciplinary case conferences, person
centered care coordination, and a cloud-based information and communications
technology (ICT) tool supporting the intervention process. The primary outcome is
quality of care for older residents using a composite measure of quality
indicators from the interRAI LTCF assessment system. Outcome assessors and data
analysts will be blinded to group assignment. Secondary outcomes include quality
of life, healthcare utilization, and cost. Process evaluation will be also
conducted. DISCUSSION: This study is expected to provide important new evidence
on the effectiveness, cost-effectiveness, and implementation process of an ICT
supported chronic care model for older persons with multiple chronic illnesses.
The SPEC intervention is also unique as the first registered trial implementing
an integrated care model using technology to promote person-centered care for
frail older nursing home residents in South Korea, where formal LTC was recently
introduced. TRIAL REGISTRATION: ISRCTN11972147.
PMID- 28420325
TI - Usefulness of grayscale inverted images in addition to standard images in digital
mammography.
AB - BACKGROUND: Mammography is essential for early diagnosis of breast cancer, which
is the most common type of cancer in females that is associated with a high
mortality rate. We investigated whether evaluation of the grayscale inverted
images of mammograms would aid in increasing the diagnostic sensitivity of the
mammographic imaging technique. METHODS: Our study included 636 mammograms of 159
women who had undergone digital mammography. Standard, grayscale inverted, and
standard plus grayscale inverted images were sequentially examined three times,
at 15-day intervals, for the presence or assessment of pathological changes in
the skin, calcification, asymmetric density, mass lesions, structural
distortions, and intramammary and axillary lymph nodes. To determine whether
grayscale inverted image assessment improved detection rates, the results of the
three assessment modes were compared using Cochran's Q test and the McNemar test
(p < 0.05 was considered statistically significant). RESULTS: The average age of
159 patients was 50.4 years (range, 35-80 years). There were significant
differences among the three assessment modes with respect to calcification and
intramammary lymph nodes (p < 0.05); however, no significant differences were
observed for the detection of other parameters. CONCLUSIONS: Assessment of
grayscale inverted images in addition to standard images facilitates the
detection of microcalcification.
PMID- 28420323
TI - Study protocol: Insight 46 - a neuroscience sub-study of the MRC National Survey
of Health and Development.
AB - BACKGROUND: Increasing age is the biggest risk factor for dementia, of which
Alzheimer's disease is the commonest cause. The pathological changes underpinning
Alzheimer's disease are thought to develop at least a decade prior to the onset
of symptoms. Molecular positron emission tomography and multi-modal magnetic
resonance imaging allow key pathological processes underpinning cognitive
impairment - including beta-amyloid depostion, vascular disease, network
breakdown and atrophy - to be assessed repeatedly and non-invasively. This
enables potential determinants of dementia to be delineated earlier, and
therefore opens a pre-symptomatic window where intervention may prevent the onset
of cognitive symptoms. METHODS/DESIGN: This paper outlines the clinical,
cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the
MRC National Survey of Health and Development. This is one of the oldest British
birth cohort studies and has followed 5362 individuals since their birth in
England, Scotland and Wales during one week in March 1946. These individuals have
been tracked in 24 waves of data collection incorporating a wide range of health
and functional measures, including repeat measures of cognitive function. Now
aged 71 years, a small fraction have overt dementia, but estimates suggest that
~1/3 of individuals in this age group may be in the preclinical stages of
Alzheimer's disease. Insight 46 is recruiting 500 study members selected at
random from those who attended a clinical visit at 60-64 years and on whom
relevant lifecourse data are available. We describe the sub-study design and
protocol which involves a prospective two time-point (0, 24 month) data
collection covering clinical, neuropsychological, beta-amyloid positron emission
tomography and magnetic resonance imaging, biomarker and genetic information.
Data collection started in 2015 (age 69) and aims to be completed in 2019 (age
73). DISCUSSION: Through the integration of data on the socioeconomic environment
and on physical, psychological and cognitive function from 0 to 69 years, coupled
with genetics, structural and molecular imaging, and intensive cognitive and
neurological phenotyping, Insight 46 aims to identify lifetime factors which
influence brain health and cognitive ageing, with particular focus on Alzheimer's
disease and cerebrovascular disease. This will provide an evidence base for the
rational design of disease-modifying trials.
PMID- 28420326
TI - Transcriptional changes induced by bevacizumab combination therapy in responding
and non-responding recurrent glioblastoma patients.
AB - BACKGROUND: Bevacizumab combined with chemotherapy produces clinical durable
response in 25-30% of recurrent glioblastoma patients. This group of patients has
shown improved survival and quality of life. The aim of this study was to
investigate changes in gene expression associated with response and resistance to
bevacizumab combination therapy. METHODS: Recurrent glioblastoma patients who had
biomarker-accessible tumor tissue surgically removed both before bevacizumab
treatment and at time of progression were included. Patients were grouped into
responders (n = 7) and non-responders (n = 14). Gene expression profiling of
formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.
RESULTS: By comparing pretreatment samples of responders with those of non
responders no significant difference was observed. In a paired comparison
analysis of pre- and posttreatment samples of non-responders 1 gene was
significantly differentially expressed. In responders, this approach revealed 256
significantly differentially expressed genes (72 down- and 184 up-regulated genes
at the time of progression). Genes differentially expressed in responders
revealed a shift towards a more proneural and less mesenchymal phenotype at the
time of progression. CONCLUSIONS: Bevacizumab combination treatment demonstrated
a significant impact on the transcriptional changes in responders; but only
minimal changes in non-responders. This suggests that non-responding
glioblastomas progress chaotically without following distinct gene expression
changes while responding tumors adaptively respond or progress by means of the
same transcriptional changes. In conclusion, we hypothesize that the identified
gene expression changes of responding tumors are associated to bevacizumab
response or resistance mechanisms.
PMID- 28420327
TI - Clinical predictors for the prognosis of myasthenia gravis.
AB - BACKGROUND: Clinical predictors for myasthenia gravis relapse and ocular
myasthenia gravis secondary generalization during the first two years after
disease onset remain incompletely identified. This study attempts to investigate
the clinical predictors for the prognosis of Myasthenia Gravis. METHODS: Eighty
three patients with myasthenia gravis were concluded in this study. Baseline
characteristics were analyzed as predictors. RESULTS: Relapse of myasthenia
gravis developed in 26 patients (34%). Generalization developed in 34 ocular
myasthenia gravis patients (85%). Other autoimmune diseases were observed more
commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group
contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients
with thymus hyperplasia progressed more rapidly than those with other thymus
pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as
ptosis or diplopia predicted early progression than concurrence of ptosis and
diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine,
thymectomy, IVIG, immunosuppressive drugs did not show significant difference
between the relapsed and non-relapsed groups. The treatment outcome also showed
no difference between the single OMG and second generalized groups. CONCLUSIONS:
Occurrence of associated autoimmune disease can serve as a potential predictor
for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic
hyperplasia can predict generalization in the first six months.
PMID- 28420328
TI - Talking about intimate partner violence in multi-cultural antenatal care: a
qualitative study of pregnant women's advice for better communication in South
East Norway.
AB - BACKGROUND: Intimate partner violence (IPV) against women constitutes a major
public health problem. Antenatal care is considered a window of opportunity to
disclose and to communicate about IPV. However, little is known about how women
from different ethnic backgrounds wish to communicate about their experiences
with IPV during pregnancy in antenatal care. The aim of the present study was to
explore how women from different ethnic backgrounds experienced IPV and what
their recommendations were about how midwives should communicate about IPV in
antenatal care. METHODS: Qualitative individual interviews with eight women who
had experienced IPV during pregnancy were conducted and analysed using thematic
analysis. The participants were purposively recruited from three crisis shelters
in South-East Norway. RESULTS: The participants either had immigrant backgrounds
(n = 5) or were ethnic Norwegians (n = 3). All participants received antenatal
care by a midwife. Although none of the participants were asked about IPV during
antenatal care, they wished to talk about their experiences. Most participants
felt that it would be important for the midwife to make them aware that they were
victims of violence. Participants offered different suggestions on how and when
midwives should talk about IPV. Facilitators to talk about IPV with the midwife
were a good relationship with and the trustworthiness of the midwife, information
about possible negative health outcomes for the newborn owing to IPV and knowing
that the midwife could help them. The main barriers to talk about IPV with the
midwife were that the participants were accompanied by their husbands during
antenatal care, fear that the Child Welfare Service would take away their
children after disclosure and cultural acceptance of violence. Participants with
immigrant backgrounds also experienced difficulties in talking about IPV owing to
their limited language skills. They thought that professionally trained
interpreters with experience of IPV could overcome this barrier. CONCLUSION: Even
though none of the participants were asked about IPV in antenatal care, they
offered different suggestions on how and when midwives should talk about IPV.
Participants irrespective of their ethnical backgrounds perceived antenatal care
as a key area to facilitate disclosure of IPV. Midwives' communication and
strategic skills to address IPV are crucial for help-seeking women. Training
midwives' skills in culture-sensitive communication might help to overcome
cultural barriers to talk about violence.
PMID- 28420329
TI - Contrast-enhanced US with Perfluorobutane(Sonazoid) used as a surveillance test
for Hepatocellular Carcinoma (HCC) in Cirrhosis (SCAN): an exploratory cross
sectional study for a diagnostic trial.
AB - BACKGROUND: Ultrasonography (US) is widely used as a standard surveillance tool
for patients who are at a high risk of having hepatocellular carcinoma (HCC);
however, conventional B-mode US appears to be insufficient in order to ensure the
early detection of HCC. Perfluorobutane allows very stable Kupffer phase imaging
for at least 60 min, which is tolerable for examinations of the entire liver. The
purpose of our study is to evaluate the added value of contrast-enhanced US using
perfluorobutane to that of conventional B-mode US as an HCC surveillance tool for
patients with liver cirrhosis. METHODS/DESIGN: SCAN (Sonazoid-US for surveillance
of hepatoCellulArcarciNoma) is a prospective, multi-institutional, diagnostic
trial using an intra-individual comparison design in a single arm of patients.
This study was approved by our five institutional review board and informed
consent was obtained from all participating. We obtained consent for publication
of these data (contrast enhanced US images, CT or MRI images, laboratory
findings, age, sex) from all participating patients. All patients will undergo
conventional B-mode US immediately followed by contrast-enhanced US. The
standardized case report forms will be completed by operating radiologists after
B-mode US and contrast-enhanced US, respectively. If any lesion(s) is detected,
the likelihood of HCC will be recorded. The primary endpoints are a detection
rate of early-stage HCC and a false referral rate of HCC. Intra-individual
comparison using Mcnemar's test will be performed between B-mode US and contrast
enhanced US. The study will include 523 patients under HCC surveillance in five
medical institutions in Korea. DISCUSSION: SCAN is the first study to investigate
the efficacy of contrast-enhanced US in surveillance using two reciprocal
endpoints specialized for the evaluation of a surveillance test. SCAN will
provide evidence regarding whether patients can truly benefit from contrast
enhanced US in terms of the detection of early stage HCC while avoiding
additional unnecessary examinations. In addition to the study protocol, we
elaborate on potentially debatable components of SCAN, including the design of an
intra-individual comparison study, study endpoints, composite reference
standards, and indefinite imaging criteria regarding the likelihood of HCC. TRIAL
REGISTRATION: The date of trial registration (ClincalTrials.gov: NCT02188901 ) in
this study is July 3, 2014. The last patient enrolled in August 30, 2016 and
follow up to see the primary end point is still ongoing. All authors have no
other relationships/conditions/circumstances that present a potential conflict of
interest of relationships. Our study protocol has undergone peer-review by the
funding body (GE Healthcare). No other relationships/conditions/circumstances
that present a potential conflict of interest. Also, we clearly stated in the
'competing interests' section of my manuscript.
PMID- 28420330
TI - Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a
primary EBV infection: a case report.
AB - BACKGROUND: Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are
detected in various demyelinating diseases, such as pediatric acute disseminated
encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody
seronegative neuromyelitis optica spectrum disorder. We present a patient who
developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM)
due to Epstein-Barr virus (EBV) infection. CASE PRESENTATION: A 36-year-old
healthy man developed paresthesia of bilateral lower extremities and urinary
retention 8 days after the onset of IM due to primary EBV infection. The MRI
revealed the lesions in the cervical spinal cord, the conus medullaris, and the
internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis.
Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of
1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly
improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG
antibody titer at the 6-month follow-up was negative. CONCLUSIONS: This case
suggests that primary EBV infection would trigger anti-MOG antibody-positive
ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of
which correlate well with the neurological symptoms.
PMID- 28420331
TI - Arsenic treatment increase Aurora-A overexpression through E2F1 activation in
bladder cells.
AB - BACKGROUND: Arsenic is a widely distributed metalloid compound that has biphasic
effects on cultured cells. In large doses, arsenic can be toxic enough to trigger
cell death. In smaller amounts, non-toxic doses may promote cell proliferation
and induces carcinogenesis. Aberration of chromosome is frequently detected in
epithelial cells and lymphocytes of individuals from arsenic contaminated areas.
Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability
and cell transformation. We have reported that low concentration (?1 MUM) of
arsenic treatment increases Aurora-A expression in immortalized bladder
urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A
activation remaining unclear. METHODS: Bromodeoxyuridine (BrdU) staining, MTT
assay, and flow cytometry assay were conducted to determine cell proliferation.
Messenger RNA and protein expression levels of Aurora-A were detected by reverse
transcriptional-PCR and Western blotting, respectively. Centrosome of cells was
observed by immunofluorescent staining. The transcription factor of Aurora-A was
investigated by promoter activity, chromosome immunoprecipitation (ChIP), and
small interfering RNA (shRNA) assays. Mouse model was utilized to confirm the
relationship between arsenic and Aurora-A. RESULTS: We reveal that low dosage of
arsenic treatment increased cell proliferation is associated with accumulated
cell population at S phase. We also detected increased Aurora-A expression at
mRNA and protein levels in immortalized bladder urothelial E7 cells exposed to
low doses of arsenic. Arsenic-treated cells displayed increased multiple
centrosome which is resulted from overexpressed Aurora-A. Furthermore, the
transcription factor, E2F1, is responsible for Aurora-A overexpression after
arsenic treatment. We further disclosed that Aurora-A expression and cell
proliferation were increased in bladder and uterus tissues of the BALB/c mice
after long-term arsenic (1 mg/L) exposure for 2 months. CONCLUSION: We reveal
that low dose of arsenic induced cell proliferation is through Aurora-A
overexpression, which is transcriptionally regulated by E2F1 both in vitro and in
vivo. Our findings disclose a new possibility that arsenic at low concentration
activates Aurora-A to induce carcinogenesis.
PMID- 28420332
TI - Genetic diversity of Elaeis oleifera (HBK) Cortes populations using cross species
SSRs: implication's for germplasm utilization and conservation.
AB - BACKGROUND: The Elaeis oleifera genetic materials were assembled from its center
of diversity in South and Central America. These materials are currently being
preserved in Malaysia as ex situ living collections. Maintaining such collections
is expensive and requires sizable land. Information on the genetic diversity of
these collections can help achieve efficient conservation via maintenance of core
collection. For this purpose, we have applied fourteen unlinked microsatellite
markers to evaluate 532 E. oleifera palms representing 19 populations distributed
across Honduras, Costa Rica, Panama and Colombia. RESULTS: In general, the
genetic diversity decreased from Costa Rica towards the north (Honduras) and
south-east (Colombia). Principle coordinate analysis (PCoA) showed a single
cluster indicating low divergence among palms. The phylogenetic tree and
STRUCTURE analysis revealed clusters based on country of origin, indicating
considerable gene flow among populations within countries. Based on the values of
the genetic diversity parameters, some genetically diverse populations could be
identified. Further, a total of 34 individual palms that collectively captured
maximum allelic diversity with reduced redundancy were also identified. High
pairwise genetic differentiation (Fst > 0.250) among populations was evident,
particularly between the Colombian populations and those from Honduras, Panama
and Costa Rica. Crossing selected palms from highly differentiated populations
could generate off-springs that retain more genetic diversity. CONCLUSION: The
results attained are useful for selecting palms and populations for core
collection. The selected materials can also be included into crossing scheme to
generate offsprings that capture greater genetic diversity for selection gain in
the future.
PMID- 28420333
TI - Strategies and cost-effectiveness evaluation of persistent albuminuria screening
among high-risk population of chronic kidney disease.
AB - BACKGROUND: Screening for persistent albuminuria among the high-risk population
is important for early detection of CKD while studies regarding screening
protocol and related cost-effectiveness analysis are limited. This study explored
a feasible and cost-efficient screening strategy for detecting persistent
albuminuria among the high-risk population. METHODS: A cohort study including 157
clinically stable outpatients with a risk factor of CKD and whose laboratory
tests revealed an albumin-creatinine-ratio (ACR) between 30 and 300 mg/g of
creatinine during the previous 12 months was conducted to assess the validity of
alternative screening strategies. Each participant collected three first morning
urine samples in three consecutive months. These samples were labeled as DAY-1,
MONTH-2 and MONTH-3. In the first month, a random spot sample in the afternoon of
the first day and another morning sample on the second day were collected and
labeled as Random and DAY-2. Persistent albuminuria was defined by abnormal ACR
(>=30 mg/g creatinine) for DAY-1, MONTH-2 and MONTH-3. Alternative strategies
were DAY-1; Random; DAY-1 + Random; DAY-1 + DAY-2; and DAY-1 + Random + DAY-2. To
evaluate the economic performance of those alternative strategies, a hybrid
decision tree/Markov model was developed based on the cohort study to simulate
both clinical and cost-effectiveness outcomes. Sensitivity analyses were
conducted to investigate assumptions of the model and to examine the model's
robustness. RESULTS: Altogether, 82 patients exhibited persistent albuminuria.
All of the five strategies had sensitivity higher than 90%. Of these strategies,
Random had the lowest specificity (46.7%), and DAY-1 + Random + DAY-2 had the
highest specificity (81.3%). Estimated cost for each quality adjusted life year
(QALYs) gained were Y112,335.88 for DAY-1 + Random, Y8134.69 for Random and
Y10,327.99 for DAY-1 + Random + DAY-2. When compared with DAY-1 strategy, the
sensitivity and specificity of which were 100.0 and 69.3%, respectively. DAY-1 +
Random + DAY-2 had the highest effectiveness and incremental effectiveness of
11.87 and 0.73 QALYs. At a willingness-to-pay threshold of Y100,000 per QALY, DAY
1 + Random + DAY-2 had the highest acceptability of 91.0%. Sensitivity analyses
demonstrated the robustness of the results. CONCLUSIONS: In order to make a quick
diagnosis of persistent albuminuria among high-risk population, the strategy of
combining two first morning urine samples and one randomized spot urine sample in
two consecutive days is accurate, saves time, and is cost-effective.
PMID- 28420334
TI - Mucormycosis in renal transplant recipients: review of 174 reported cases.
AB - BACKGROUND: Mucormycosis is a highly lethal fungal infection especially in
immunocompromised individuals. METHODS: In order to review the epidemiology,
diagnosis, and treatment of mucormycosis in renal transplant recipients we
searched publications of mucormycosis cases in renal transplant recipients in
PUBMED database up to December 2015. RESULTS: A total of 174 cases in renal
transplant recipients were included in this review. Most of the cases (76%) were
male. Major underlying diseases were diabetes mellitus (43.1%). Rhinocerebral was
the most common site of infection (33.3%). Rhizopus species was the most frequent
fungus (59.1%) in patients with pathogen identified to species level. The
mortality rates of disseminated mucormycosis (76.0%) and graft renal (55.6%) were
higher than infection in other sites. The overall survival in patients received
surgical debridement combined with amphotericin B/posaconazole (70.2%) was higher
than those who received antifungal therapy alone (32.4%), surgery alone (36.4%)
or without therapy (0%) (p < 0.001). The overall survivals in patients receiving
posaconazole and lipid amphoterincin B were higher than that receiving
deoxycholate formulation (92.3% and 73.4% vs 47.4%). CONCLUSIONS: Mucormycosis is
a severe infection in renal transplant recipients. Surgical debridement combined
with antifungals, especially liposomal amphotericin B and posaconazole, can
significantly improve patient's overall survival.
PMID- 28420335
TI - Trajectories of Life Satisfaction and their Predictors among Korean Older Adults.
AB - BACKGROUND: Among older adults, life satisfaction (LS) correlates with health,
mortality, and successful ageing. As various potential threats to LS tend to
increase with advancing years, patterns of age-related changes in LS among older
adults remain inconsistent. This study aimed to identify LS trajectories in older
adults and the characteristics of individuals who experience them. METHODS: Large
scale, nationally representative, longitudinal data collected from 2005 to 2013
were analyzed for this study. The outcome measure was a summary of
multidimensional domains influencing LS: health, finance, housing, neighbor
relationships, and family relationships. Latent class growth models and logistic
regression models were used to identify trajectory groups and their predictors,
respectively. RESULTS: Within 3517 individuals aged 65 or older, five
trajectories were identified across eight follow-up years: "low-stable" (TG1; n =
282; 8%), "middle-stable" (TG2; n = 1146; 32.6%), "improving" (TG3; n = 75;
2.1%), "upper middle-stable" (TG4; n = 1653; 47%), and "high" (TG5; n = 361;
10.3%). High trajectory individuals more frequently had higher education,
financial security, good physical health, and good mental health than those in
the stable, but less satisfied, groups. Similarly, compared to the largest group
(upper middle-stable trajectory), individuals in the low-stable or middle-stable
trajectory group not only had poorer physical and mental health but were more
likely to be living alone, financially stressed, and residing in urban locations.
Individuals with improving trajectory were younger and in poorer mental health at
baseline compared to the upper middle-stable trajectory group. CONCLUSION: Life
satisfaction in the older follows distinct trajectories. For older adults,
trajectories are stable over time and predictable, in part, from individual
characteristics. Knowledge of these patterns is important for effective policy
and program development.
PMID- 28420336
TI - Reduced changes in protein compared to mRNA levels across non-proliferating
tissues.
AB - BACKGROUND: The quantitative relations between RNA and protein are fundamental to
biology and are still not fully understood. Across taxa, it was demonstrated that
the protein-to-mRNA ratio in steady state varies in a direction that lessens the
change in protein levels as a result of changes in the transcript abundance.
Evidence for this behavior in tissues is sparse. We tested this phenomenon in new
data that we produced for the mouse auditory system, and in previously published
tissue datasets. A joint analysis of the transcriptome and proteome was performed
across four datasets: inner-ear mouse tissues, mouse organ tissues,
lymphoblastoid primate samples and human cancer cell lines. RESULTS: We show that
the protein levels are more conserved than the mRNA levels in all datasets, and
that changes in transcription are associated with translational changes that
exert opposite effects on the final protein level, in all tissues except cancer.
Finally, we observe that some functions are enriched in the inner ear on the mRNA
level but not in protein. CONCLUSIONS: We suggest that partial buffering between
transcription and translation ensures that proteins can be made rapidly in
response to a stimulus. Accounting for the buffering can improve the prediction
of protein levels from mRNA levels.
PMID- 28420337
TI - Right aortic arch analysis - Anatomical variant or serious vascular defect?
AB - BACKGROUND: The right-sided aortic arch (RAA) is a rare congenital defect of the
aorta. The aim of the study was to assess the occurrence of RAA in diagnoses
performed by the University Radiology Department and analyze the frequency of
concomitant vascular abnormalities. METHODS: The database of the Radiology
Department was retrospectively analyzed between January 2008 and May 2016 with
the keyword "right aortic arch". Twenty patients with this diagnosis were
identified from a total of 11,690 CT examinations of the chest area, 19,623 CT
examinations of brain-supplying vessels, and 1863 MRI examinations of the heart
and aortic arch or brain-supplying arteries. The type of aortic arch, the
occurrence of Kommerell's diverticulum and possible other vascular abnormalities,
such as stenosis, kinking or occlusion, were then investigated. RESULTS: The
analysis identified nine patients with type I and 11 patients with type II RAA.
Eight of the 11 type II patients presented Kommerell's diverticulum. Concomitant
vascular abnormalities were detected in four patients with type II RAA. In two
cases, the right common carotid artery (RCCA) was narrowed by up to 80%, with
steal phenomenon confirmed in one of them. In the second coincident right
subclavian artery (RSA) stenosis was depicted. In two other cases, the aberrant
left subclavian arteries (ALSA) were found to be narrowed at the level of origin
by up to 70%. One patient was found with type B aortic dissection including ALSA
and Kommerell's diverticulum. CONCLUSIONS: Our observations indicate that
concomitant vascular abnormalities may occur more often than reported in
literature. Patients diagnosed with type II RAA should be examined with Doppler
ultrasonography to identify coincident vascular disorders, especially stenosis of
the common carotid arteries or subclavian arteries.
PMID- 28420338
TI - Review and evaluation of performance measures for survival prediction models in
external validation settings.
AB - BACKGROUND: When developing a prediction model for survival data it is essential
to validate its performance in external validation settings using appropriate
performance measures. Although a number of such measures have been proposed,
there is only limited guidance regarding their use in the context of model
validation. This paper reviewed and evaluated a wide range of performance
measures to provide some guidelines for their use in practice. METHODS: An
extensive simulation study based on two clinical datasets was conducted to
investigate the performance of the measures in external validation settings.
Measures were selected from categories that assess the overall performance,
discrimination and calibration of a survival prediction model. Some of these have
been modified to allow their use with validation data, and a case study is
provided to describe how these measures can be estimated in practice. The
measures were evaluated with respect to their robustness to censoring and ease of
interpretation. All measures are implemented, or are straightforward to
implement, in statistical software. RESULTS: Most of the performance measures
were reasonably robust to moderate levels of censoring. One exception was
Harrell's concordance measure which tended to increase as censoring increased.
CONCLUSIONS: We recommend that Uno's concordance measure is used to quantify
concordance when there are moderate levels of censoring. Alternatively, Gonen and
Heller's measure could be considered, especially if censoring is very high, but
we suggest that the prediction model is re-calibrated first. We also recommend
that Royston's D is routinely reported to assess discrimination since it has an
appealing interpretation. The calibration slope is useful for both internal and
external validation settings and recommended to report routinely. Our
recommendation would be to use any of the predictive accuracy measures and
provide the corresponding predictive accuracy curves. In addition, we recommend
to investigate the characteristics of the validation data such as the level of
censoring and the distribution of the prognostic index derived in the validation
setting before choosing the performance measures.
PMID- 28420339
TI - Protocol for the development of a salutogenic intrapartum core outcome set
(SIPCOS).
AB - BACKGROUND: Maternity intrapartum care research and clinical care more often
focus on outcomes that minimise or prevent adverse health rather than on what
constitutes positive health and wellbeing (salutogenesis). This was highlighted
recently in a systematic review of reviews of intrapartum reported outcomes where
only 8% of 1648 individual outcomes, from 102 systematic reviews, were agreed as
being salutogenically-focused. Added to this is variation in the outcomes
measured in individual studies rendering it very difficult for researchers to
synthesise, fully, the evidence from studies on a particular topic. One of the
suggested ways to address this is to develop and apply an agreed standardised set
of outcomes, known as a 'core outcome set' (COS). In this paper we present a
protocol for the development of a salutogenic intrapartum COS (SIPCOS) for use in
maternity care research and a SIPCOS for measuring in daily intrapartum clinical
care. METHODS: The study proposes three phases in developing the final SIPCOSs.
Phase one, which is complete, involved the conduct of a systematic review of
reviews to identify a preliminary list of salutogenically-focused outcomes that
had previously been reported in systematic reviews of intrapartum interventions.
Sixteen unique salutogenically-focused outcome categories were identified. Phase
two will involve prioritising these outcomes, from the perspective of key
stakeholders (users of maternity services, clinicians and researchers) by asking
them to rate the importance of each outcome for inclusion in the SIPCOSs. A final
consensus meeting (phase three) will be held, bringing international stakeholders
together to review the preliminary SIPCOSs resulting from the survey and to agree
and finalise the final SIPCOSs for use in future maternity care research and
daily clinical care. DISCUSSION: The expectation in developing the SIPCOSs is
that they will be collected and reported in all future studies evaluating
intrapartum interventions and measured/recorded in future intrapartum clinical
care, as routine, alongside other outcomes also deemed important in the context
of the study or clinical scenario. Using the SIPCOSs in this way, will promote
and encourage standardised measurements of positive health outcomes in maternity
care, into the future.
PMID- 28420340
TI - Genetics and mapping of a new anthracnose resistance locus in Andean common bean
Paloma.
AB - BACKGROUND: The Andean cultivar Paloma is resistant to Mesoamerican and Andean
races of Colletotrichum lindemuthianum, the fungal pathogen that causes the
destructive anthracnose disease in common bean. Remarkably, Paloma is resistant
to Mesoamerican races 2047 and 3481, which are among the most virulent races of
the anthracnose pathogen. Most genes conferring anthracnose resistance in common
bean are overcome by these races. The genetic mapping and the relationship
between the resistant Co-Pa gene of Paloma and previously characterized
anthracnose resistance genes can be a great contribution for breeding programs.
RESULTS: The inheritance of resistance studies for Paloma was performed in F2
population from the cross Paloma (resistant) * Cornell 49-242 (susceptible)
inoculated with race 2047, and in F2 and F2:3 generations from the cross Paloma
(resistant) * PI 207262 (susceptible) inoculated with race 3481. The results of
these studies demonstrated that a single dominant gene confers the resistance in
Paloma. Allelism tests performed with multiple races of C. lindemuthianum showed
that the resistance gene in Paloma, provisionally named Co-Pa, is independent
from the anthracnose resistance genes Co-1, Co-2, Co-3, Co-4, Co-5, Co-6, Co-12,
Co-13, Co-14, Co-15 and Co-16. Bulk segregant analysis using the SNP chip
BARCBean6K_3 positioned the approximate location of Co-Pa in the lower arm of
chromosome Pv01. Further mapping analysis located the Co-Pa gene at a 390 kb
region of Pv01 flanked by SNP markers SS82 and SS83 at a distance of 1.3 and 2.1
cM, respectively. CONCLUSIONS: The results presented here showed that Paloma
cultivar has a new dominant gene conferring resistance to anthracnose, which is
independent from those genes previously described. The linkage between the Co-Pa
gene and the SS82 and SS83 SNP markers will be extremely important for marker
assisted introgression of the gene into elite cultivars in order to enhance
resistance.
PMID- 28420341
TI - Genetic sequence-based prediction of long-range chromatin interactions suggests a
potential role of short tandem repeat sequences in genome organization.
AB - BACKGROUND: Knowing the three-dimensional (3D) structure of the chromatin is
important for obtaining a complete picture of the regulatory landscape. Changes
in the 3D structure have been implicated in diseases. While there exist
approaches that attempt to predict the long-range chromatin interactions, they
focus only on interactions between specific genomic regions - the promoters and
enhancers, neglecting other possibilities, for instance, the so-called structural
interactions involving intervening chromatin. RESULTS: We present a method that
can be trained on 5C data using the genetic sequence of the candidate loci to
predict potential genome-wide interaction partners of a particular locus of
interest. We have built locus-specific support vector machine (SVM)-based
predictors using the oligomer distance histograms (ODH) representation. The
method shows good performance with a mean test AUC (area under the receiver
operating characteristic (ROC) curve) of 0.7 or higher for various regions across
cell lines GM12878, K562 and HeLa-S3. In cases where any locus did not have
sufficient candidate interaction partners for model training, we employed
multitask learning to share knowledge between models of different loci. In this
scenario, across the three cell lines, the method attained an average performance
increase of 0.09 in the AUC. Performance evaluation of the models trained on 5C
data regarding prediction on an independent high-resolution Hi-C dataset (which
is a rather hard problem) shows 0.56 AUC, on average. Additionally, we have
developed new, intuitive visualization methods that enable interpretation of
sequence signals that contributed towards prediction of locus-specific
interaction partners. The analysis of these sequence signals suggests a potential
general role of short tandem repeat sequences in genome organization.
CONCLUSIONS: We demonstrated how our approach can 1) provide insights into
sequence features of locus-specific interaction partners, and 2) also identify
their cell-line specificity. That our models deem short tandem repeat sequences
as discriminative for prediction of potential interaction partners, suggests that
they could play a larger role in genome organization. Thus, our approach can (a)
be beneficial to broadly understand, at the sequence-level, chromatin
interactions and higher-order structures like (meta-) topologically associating
domains (TADs); (b) study regions omitted from existing prediction approaches
using various information sources (e.g., epigenetic information); and
PMID- 28420342
TI - Impact of correlation of predictors on discrimination of risk models in
development and external populations.
AB - BACKGROUND: The area under the ROC curve (AUC) of risk models is known to be
influenced by differences in case-mix and effect size of predictors. The impact
of heterogeneity in correlation among predictors has however been under
investigated. We sought to evaluate how correlation among predictors affects the
AUC in development and external populations. METHODS: We simulated hypothetical
populations using two different methods based on means, standard deviations, and
correlation of two continuous predictors. In the first approach, the distribution
and correlation of predictors were assumed for the total population. In the
second approach, these parameters were modeled conditional on disease status. In
both approaches, multivariable logistic regression models were fitted to predict
disease risk in individuals. Each risk model developed in a population was
validated in the remaining populations to investigate external validity. RESULTS:
For both approaches, we observed that the magnitude of the AUC in the development
and external populations depends on the correlation among predictors. Lower AUCs
were estimated in scenarios of both strong positive and negative correlation,
depending on the direction of predictor effects and the simulation method.
However, when adjusted effect sizes of predictors were specified in the opposite
directions, increasingly negative correlation consistently improved the AUC. AUCs
in external validation populations were higher or lower than in the derivation
cohort, even in the presence of similar predictor effects. CONCLUSIONS:
Discrimination of risk prediction models should be assessed in various external
populations with different correlation structures to make better inferences about
model generalizability.
PMID- 28420343
TI - On the association analysis of CNV data: a fast and robust family-based
association method.
AB - BACKGROUND: Copy number variation (CNV) is known to play an important role in the
genetics of complex diseases and several methods have been proposed to detect
association of CNV with phenotypes of interest. Statistical methods for CNV
association analysis can be categorized into two different strategies. First, the
copy number is estimated by maximum likelihood and association of the expected
copy number with the phenotype is tested. Second, the observed probe intensity
measurements can be directly used to detect association of CNV with the
phenotypes of interest. RESULTS: For each strategy we provide a statistic that
can be applied to extended families. The computational efficiency of the proposed
methods enables genome-wide association analysis and we show with simulation
studies that the proposed methods outperform other existing approaches. In
particular, we found that the first strategy is always more efficient than the
second strategy no matter whether copy numbers for each individual are well
identified or not. With the proposed methods, we performed genome-wide CNV
association analyses of hematological trait, hematocrit, on 521 Korean family
samples. CONCLUSIONS: We found that statistical analysis with the expected copy
number is more powerful than the statistic with the probe intensity measurements
regardless of the accuracy of the estimation of copy numbers.
PMID- 28420344
TI - Erratum to: The JBEI quantitative metabolic modeling library (jQMM): a python
library for modeling microbial metabolism.
PMID- 28420345
TI - Selective sweep with significant positive selection serves as the driving force
for the differentiation of japonica and indica rice cultivars.
AB - BACKGROUND: Asian cultivated rice (Oryza sativa L.), including japonica and
indica, is unarguable the most important crop in Asia as well as worldwide.
However, a decisive conclusion of its origination and domestication processes are
still lacking. Nowadays, the ever-increasing high-throughput sequencing data of
numerous rice samples have provided us new opportunities to get close to the
answer of these questions. RESULTS: By compiling 296 whole-genome sequenced rice
cultivars and 39 diverse wild rice, two types of domesticated regions (DR-I and
DR-II) with strong selective sweep signals between different groups were
detected. DR-I regions included 28 blocks which significantly differentiated
between japonica and indica subspecies, while DR-II regions were consisted of
another 28 blocks which significantly differentiated between wild and cultivated
rice, each covered 890 kb and 640 kb, respectively. In-depth analysis suggested
that both DR-Is and DR-IIs could have originated from Indo-China Peninsula to
southern China, and DR-IIs might be introgressed from indica to japonica.
Functional bias with significant positive selection has also been detected in the
genes of DR-I, suggesting important role of the selective sweep in
differentiation of japonica and indica. CONCLUSIONS: This research promoted a new
possible model of the origin of the cultivated rice that DR-Is in japonica and
indica maybe independently originated from the divergent wild rice in the Indo
China Peninsula to southern China, and then followed by frequent introgression.
Genes with significant positive selection and biased functions were also detected
which could play important roles in rice domestication and differentiation
processes.
PMID- 28420347
TI - Kappa statistic to measure agreement beyond chance in free-response assessments.
AB - BACKGROUND: The usual kappa statistic requires that all observations be
enumerated. However, in free-response assessments, only positive (or abnormal)
findings are notified, but negative (or normal) findings are not. This situation
occurs frequently in imaging or other diagnostic studies. We propose here a kappa
statistic that is suitable for free-response assessments. METHOD: We derived the
equivalent of Cohen's kappa statistic for two raters under the assumption that
the number of possible findings for any given patient is very large, as well as a
formula for sampling variance that is applicable to independent observations (for
clustered observations, a bootstrap procedure is proposed). The proposed
statistic was applied to a real-life dataset, and compared with the common
practice of collapsing observations within a finite number of regions of
interest. RESULTS: The free-response kappa is computed from the total numbers of
discordant (b and c) and concordant positive (d) observations made in all
patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging
procedures in children that were evaluated by 2 independent raters, the free
response kappa statistic was 0.820. Aggregation of results within regions of
interest resulted in overestimation of agreement beyond chance. CONCLUSIONS: The
free-response kappa provides an estimate of agreement beyond chance in situations
where only positive findings are reported by raters.
PMID- 28420346
TI - Linoleic acid: Is this the key that unlocks the quantum brain? Insights linking
broken symmetries in molecular biology, mood disorders and personalistic
emergentism.
AB - In this paper we present a mechanistic model that integrates subneuronal
structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins
and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain.
We also argue that subtle changes in the composition of the membrane's fatty
acids may lead to down-stream effects causing dysregulation of the membrane,
cytoskeleton and their interface. Such exquisite sensitivity to minor changes is
known to occur in physical systems undergoing phase transitions, the simplest and
most studied of them is the so-called Ising model, which exhibits a phase
transition at a finite temperature between an ordered and disordered state in 2-
or 3-dimensional space. We propose this model in the context of neuronal dynamics
and further hypothesize that it may involve quantum degrees of freedom dependent
upon variation in membrane domains associated with ion channels or microtubules.
Finally, we provide a link between these physical characteristics of the
dynamical mechanism to psychiatric disorders such as major depression and
antidepressant action.
PMID- 28420348
TI - Lower incidence of contrast-induced nephropathy in patients undergoing
fluorescent angiography.
AB - BACKGROUND: To evaluate the incidence and risk factors of contrast-induced
nephropathy (CIN) in patients undergoing fluorescein angiography (FA). METHODS:
One hundred sixty patients who underwent FA as a part of ophthalmic examination
and had serum creatinine (SCr) results within 24 h before FA and within 72 h
after FA between 2005 and 2013 at a tertiary medical center were included.
According to baseline SCr levels, the subjects were divided into low-risk group
(<1.5 mg/dL), intermediate-risk group (1.5-2.0 mg/dL), and high-risk group (>2.0
mg/dL) for CIN development. The CIN incidence, and changes in renal function
defined by SCr levels and estimated glomerular filtration rate (eGFR) were
evaluated. Demographics and comorbidities were analyzed to investigate an
association with CIN development. RESULTS: Of 160 patients, 91 were males
(56.9%). The mean age was 52.46 +/- 17.81 years. Two (1.3%) patients developed
CIN after FA, whose SCr levels returned to normal within 10 days without
hemodialysis. Overall, there were no changes before and after FA in SCr level
(1.52 +/- 1.31 mg/dL vs. 1.51 +/- 1.28 mg/dL, respectively; p = 0.93) and eGFR
(67.02 +/- 36.62 mL/min/1.73 m2 vs. 66.41 +/- 36.54 mL/min/1.73 m2, respectively;
p = 0.54). SCr level and eGFR remained unchanged after FA in low-risk and
intermediate-risk groups. In high-risk group, eGFR remined unchanged, but SCr
level decreased after FA (from 3.64 +/- 1.59 mg/dL to 3.53 +/- 1.60 mg/dL; p =
0.04). Basline SCr and cormorbidities did not predict CIN development.
CONCLUSIONS: Acute renal function deterioration was not evident in patients
undergoing FA regardless of baseline renal function and comorbidities.
PMID- 28420349
TI - Grey literature in systematic reviews: a cross-sectional study of the
contribution of non-English reports, unpublished studies and dissertations to the
results of meta-analyses in child-relevant reviews.
AB - BACKGROUND: Systematic reviews (SRs) are an important source of information about
healthcare interventions. A key component of a well-conducted SR is a
comprehensive literature search. There is limited evidence on the contribution of
non-English reports, unpublished studies, and dissertations and their impact on
results of meta-analyses. METHODS: Our sample included SRs from three Cochrane
Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID),
Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes
included: 1) proportion of reviews that searched for and included each study
type; 2) proportion of relevant studies represented by each study type; and 3)
impact on results and conclusions of the primary meta-analysis for each study
type. RESULTS: Most SRs searched for non-English studies; however, these were
included in only 12% of reviews and represented less than 5% of included studies.
There was a change in results in only four reviews (total sample = 129); in two
cases the change did not have an impact on the statistical or clinical
significance of results. Most SRs searched for unpublished studies but the
majority did not include these (only 6%) and they represented 2% of included
studies. In most cases the impact of including unpublished studies was small; a
substantial impact was observed in one case that relied solely on unpublished
data. Few reviews in ARI (9%) and ID (3%) searched for dissertations compared to
65% in DPLP. Overall, dissertations were included in only nine SRs and
represented less than 2% of included studies. In the majority of cases the change
in results was negligible or small; in the case where a large change was noted,
the estimate was more conservative without dissertations. CONCLUSIONS: The
majority of SRs searched for non-English and unpublished studies; however, these
represented a small proportion of included studies and rarely impacted the
results and conclusions of the review. Inclusion of these study types may have an
impact in situations where there are few relevant studies, or where there are
questionable vested interests in the published literature. We found substantial
variation in whether SRs searched for dissertations; in most reviews that
included dissertations, these had little impact on results.
PMID- 28420350
TI - Trends in baseline CD4 cell counts and risk factors for late antiretroviral
therapy initiation among HIV-positive patients in Shanghai, a retrospective cross
sectional study.
AB - BACKGROUNDS: There are few studies focus on the factors underlying the late
initiation of ART in China. We analyzed the trends in the median CD4 cell counts
among different patient groups over time and the risk factors for the late
initiation of ART in Shanghai, China. METHODS: A retrospective cross-sectional
survey was made in the Department of Infectious Disease of Shanghai Public Health
Clinical Center which is a designated diagnosis and treatment center for HIV
positive patients in Shanghai during the period of January 1st, 2008--June 30th,
2014. Late ART initiation was defined as a CD4 cell count <200 cells/mm3 or
having a clinical AIDS diagnosis prior to ART initiation. Trends in the median
CD4 cell count at ART initiation and the proportion of late ART initiation by
year were evaluated using Spearman's correlations and Chi-squared methods,
respectively. We used a logistic regression model to analyze the risk factors for
late ART initiation. The related factors collected in the multivariate model were
the patient's age, gender, infection routes and marital status. RESULTS: A total
of 3796 patients were analyzed in this study, with a median baseline CD4 cell
count of 205 cells/mm3 [interquartile range: 75-287]. The median CD4 cell counts
of patients initiating ART late increased from 76 cells/mm3 in 2008 to 103
cells/mm3 in 2014 (p < 0.001), and the proportion of late ART initiation
decreased from 80% to 45% (p < 0.001). The risk factors for late ART initiation
were male gender, heterosexual transmission and older age (>30 years) (p <
0.001). CONCLUSIONS: Notable improvements were made in the median CD4 cell count
at ART initiation and the proportion of late ART initiation from 2008 to 2014.
However, persons with high risk of HIV exposure who are male, older even
heterosexual orientation should be given more opportunities to receive frequently
screening, earlier diagnoses and timely treatment.
PMID- 28420351
TI - Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial
cells of patients with early breast cancer.
AB - BACKGROUND: Tumor epithelial cells (TEpCs) and spindle-shaped stromal cells, not
associated with the vasculature, of patients with early breast cancer express
osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL), receptor activator of nuclear factor kappa B ligand, stromal cell
derived factor-1, interleukin-6, macrophage colony stimulating factor, chemokine
(C-C motif) ligand-2 (CCL-2) and their receptors at significantly higher levels
compared with non-neoplastic breast tissues. We evaluated the clinicopathological
significance of these ligands and receptors in TEpC and spindle-shaped stromal
cells, not associated with the vasculature, to determine their impact on
prognosis of patients with early-stage breast cancer. METHODS: We conducted
immunohistochemical analyses of protein expression in primary tumors of patients
with early breast cancer and analyzed their association with standard prognostic
parameters and clinical outcomes, including local relapse, metastatic recurrence,
disease-free survival (DFS), metastasis-free survival (MFS), and overall survival
(OS). RESULTS: Elevated levels of TRAIL-R3 and chemokine (C-C motif) receptor 2
(CCR-2) in TEpCs and OPG and CCL-2 in stromal cells were significantly associated
with a higher risk of metastasis (p = 0.032, p = 0.003, p = 0.038, and p = 0.049;
respectively). Moreover, high expression of TRAIL-R3 and CCR-2 in TEpCs was
associated with shorter DFS, MFS, and OS. High TRAIL-R3 expression in TEpCs was
an independent prognostic factor for DFS and OS, and high CCR-2 expression in
these cells was an independent prognostic factor for MFS. CONCLUSIONS: High
levels of TRAIL-R3 and CCR-2 expression in TEpCs identified patients with early
breast cancer with poor outcomes.
PMID- 28420352
TI - Assessing the reliability of self-reported weight for the management of heart
failure: application of fraud detection methods to a randomised trial of
telemonitoring.
AB - BACKGROUND: Since clinical management of heart failure relies on weights that are
self-reported by the patient, errors in reporting will negatively impact the
ability of health care professionals to offer timely and effective preventive
care. Errors might often result from rounding, or more generally from individual
preferences for numbers ending in certain digits, such as 0 or 5. We apply fraud
detection methods to assess preferences for numbers ending in these digits in
order to inform medical decision making. METHODS: The Telemonitoring to Improve
Heart Failure Outcomes trial tested an approach to telemonitoring that used
existing technology; intervention patients (n = 826) were asked to measure their
weight daily using a digital scale and to relay measurements using their
telephone keypads. First, we estimated the number of weights subject to end-digit
preference by dividing the weights by five and comparing the resultant
distribution with the uniform distribution. Then, we assessed the characteristics
of patients reporting an excess number of weights ending in 0 or 5, adjusting for
chance reporting of these values. RESULTS: Of the 114,867 weight readings
reported during the trial, 18.6% were affected by end-digit preference, and the
likelihood of these errors occurring increased with the number of days that had
elapsed since trial enrolment (odds ratio per day: 1.002, p < 0.001). At least
105 patients demonstrated end-digit preference (14.9% of those who submitted
data); although statistical significance was limited, a pattern emerged that,
compared with other patients, they tended to be younger, male, high school
graduates and on more medications. Patients with end-digit preference reported
greater variability in weight, and they generated an average 2.9 alerts to the
telemonitoring system over the six-month trial period (95% CI, 2.3 to 3.5),
compared with 2.3 for other patients (95% CI, 2.2 to 2.5). CONCLUSIONS: As well
as overshadowing clinically meaningful changes in weight, end-digit preference
can lead to false alerts to telemonitoring systems, which may be associated with
unnecessary treatment and alert fatigue. In this trial, end-digit preference was
common and became increasingly so over time. By applying fraud detection methods
to electronic medical data, it is possible to produce clinically significant
information that can inform the design of initiatives to improve the accuracy of
reporting. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT00303212
March 2006.
PMID- 28420353
TI - The influence of fatigue and chronic low back pain on muscle recruitment patterns
following an unexpected external perturbation.
AB - BACKGROUND: Chronic low back pain (CLBP) has been associated with altered trunk
muscle responses as well as increased muscle fatigability. CLBP patients and
fatigued healthy subjects could experience similar neuromuscular strategies to
attempt to protect the spine. The current study examined muscle activation
differences between healthy and CLBP subjects following a perturbation. In
addition, the possible role of muscle fatigue was evaluated by investigating the
healthy control subjects in a non-fatigued and a fatigued condition. Both
experiments were combined to evaluate possible similar strategies between CLBP
and fatigued samples. METHODS: Cross-sectional study where 24 CLBP subjects and
26 healthy subjects were evaluated. Both groups (CLBP vs. healthy) and both
conditions (non-fatigued and a fatigued condition) were evaluated while a weight
was suddenly dropped on a held tray. Erector spinae, multifidus, obliques and
biceps brachii were recorded using surface electromyography. Variables describing
the bursts timing and variables describing the amount of muscle activity (number
of bursts and amplitude increase) post impact were studied. The analysis between
groups and conditions was carried out using ANOVAs with repeated measurements for
the muscle factor. RESULTS: CLBP subjects reacted similarly to healthy subjects
regarding muscle activity post impact. However, the CLBP group showed temporal
characteristics of muscle activity that were in between the fatigued and non
fatigued healthy group. Clear differences in muscle activity were displayed for
healthy subjects. Fatigued healthy subjects presented more reduced activity after
impact (upper limb and trunk muscles) than non-fatigued healthy subjects and
different temporal characteristic in the same way than CLBP patients. This same
temporal characteristic with CLBP and healthy fatigued people was a delay of the
first burst of muscle activity after impact. CONCLUSION: Though similar muscle
pattern existed between CLBP and healthy people, CLBP temporal characteristics of
muscle activity showed a pattern in between healthy people and fatigued healthy
people. While the temporal muscle pattern dysfunction used by CLBP subjects could
be related to maladaptive patterns, temporal and muscle activity characteristics
used by healthy fatigued people may lead to back injuries.
PMID- 28420354
TI - Therapeutic potentials of Crataegus azarolus var. eu- azarolus Maire leaves and
its isolated compounds.
AB - BACKGROUND: Hyperglycemia is a complicated condition accompanied with high
incidence of infection and dyslipidemia. This study aimed to explore the phyto
constituents of Crataegus azarolus var. eu- azarolus Maire leaves, and to
evaluate the therapeutic potentials particularly antimicrobial, antihyperglycemic
and antihyperlipidemic of the extract and the isolated compound (3beta-O-acetyl
ursolic acid). METHODS: Total phenolics and flavonoidal contents were measured by
RP-HPLC analysis. Free radicals scavenging activity of different extraction
solvents was tested in-vitro on DPPH free radicals. The antimicrobial activity of
the ethanolic extract and its fractions as well as the isolated compounds were
evaluated in-vitro on variable microorganisms. Animal models were used to
evaluate the antihyperglycemic and antihyperlipidemic activities of the ethanolic
extract along with the isolated compound (3beta-O acetyl ursolic acid). RESULTS:
RP- HPLC analysis of the phenolics revealed high content of rutin, salicylic and
ellagic acids. Six compounds belonging to triterpenes and phenolics were isolated
from chloroform and n-butanol fractions namely: ursolic acid, 3beta-O-acetyl
ursolic acid, ellagic acid, quercetin 3-O-beta methyl ether, rutin and apigenin7
O-rutinoside. Ethanolic extract showed the highest DPPH radical scavenger
activity compared to other solvents. Ethanolic extract, hexane fraction, ursolic
acid, 3beta-O acetyl ursolic acid and quercetin 3-O-methyl ether showed variable
antimicrobial activity against E. coli, P. aeruginosa, S. aureus, and C.
albicans. Administration of the ethanolic extract or 3beta-O acetyl ursolic acid
orally to the mice reduced blood glucose significantly in a time- and dose
dependent manner. Ethanolic extract significantly reduced LDL-C, VLDL-C, TC and
TG and increased HDL-C in rats. Ethanolic extract and 3beta-O acetyl ursolic acid
reduced in-vitro activity of pancreatic lipase. CONCLUSION: This study reveals
that Crataegus azarolus var. eu- azarolus Maire has the efficiency to control
hyperglycemia with its associated complications. This study is the first to
evaluate antihyperglycemic and antihyperlipidemic potentials of 3beta-O acetyl
ursolic acid.
PMID- 28420355
TI - Facilitators and barriers to using physical activity smartphone apps among
Chinese patients with chronic diseases.
AB - BACKGROUND: Smartphones and their applications (apps) impact society and health
care. With the growth of smartphone users and app downloads in China, patients
with chronic diseases have access to a self-management strategy for physical
activity. Although studies report physical activity apps improve the physical
activity of patients, data is limited concerning their use of these apps.
Therefore, this study investigated the current usage, willingness to use, and
barriers to using physical activity apps of Chinese patients with chronic
diseases. METHODS: We designed a questionnaire to collect data from chronic
disease patients in a tertiary hospital in Beijing, which was sent to 250
patients in four departments. RESULTS: Two hundred eighteen questionnaires were
returned (87.2% response rate). Most (92.7%) respondents owned a smartphone,
34.9% had used a physical activity app, and 18.8% were current users.
Additionally, 53.7% were willing to use a physical activity app designed for
them. Respondents more likely to use physical activity apps were younger (i.e.,
<= 44 years), more educated, current smartphone users, and previous users of
physical activity apps; moreover, they believed they needed exercise, their
disease required exercise instruction and support, and their physical status
needed monitored when exercising (p < 0.05). Main barriers to using apps reported
were insufficient function, difficulty of use, extra cost, and security issues.
CONCLUSIONS: Our results indicate sizeable smartphone ownership among Chinese
patients with chronic diseases; moreover, over half of our participants report
they would use a physical activity app designed for them. This information can be
leveraged by healthcare workers managing patients with chronic diseases.
PMID- 28420356
TI - An assessment of the HIV/TB knowledge and skills of home-based carers working in
the North West province in South Africa: a cross-sectional study.
AB - BACKGROUND: Home-based carers (HBCs) play a critical role in ensuring the success
of the primary health care re-engineering strategy in South Africa. Their role
includes ensuring improved access to and delivery of primary health care at the
household level, and better co-ordination and improved linkages between community
and health facilities for HIV/TB services. The objective of this study was to
assess the knowledge, skills, challenges and training needs of HBCs involved in
HIV/TB care in one sub-district in the North-West province of South Africa.
METHODS: We conducted a descriptive, cross-sectional study in which 157 HBCs were
interviewed to assess their knowledge and skills regarding HIV and TB. Data were
collected using a pre-tested semi-structured questionnaire. Quantitative and
qualitative data were analysed using SPSS statistical software and thematic
analysis respectively. RESULTS: One hundred and forty-four (92%) of the
interviewees were female and 13 (8%) were male. The median age of the
participants was 35 years (interquartile range (IQR): 22-27). The median score
for knowledge of both HIV and TB questions was 66% (IQR: 57-75). In general, HIV
knowledge scores were higher than TB knowledge scores (73% versus 66%). A
significant association was found between knowledge scores and formal training (p
< 0.05), and knowledge scores and highest educational levels (p < 0.05).
Irrespective of knowledge, HBCs reported providing a variety of services to
support HIV/TB services in the communities in which they worked. HBCs also
reported facing various challenges in their jobs related to stigma and the social
contexts in which they work. CONCLUSION: The study showed that the overall
knowledge of HBCs was limited, given the skills required and the services they
provide. Given the increasing role of HBCs in various health initiatives,
targeted interventions are required to support and improve their competencies and
service provision.
PMID- 28420357
TI - In search of quality indicators for Down syndrome healthcare: a scoping review.
AB - BACKGROUND: The medical care chain around Down syndrome (DS) is complex, with
many multidisciplinary challenges. The current quality of care is unknown.
Outcome-oriented quality indicators have the potential to improve medical
practice and evaluate whether innovations are successful. This is particularly
interesting for the evolving care for people with DS and intellectual
disabilities (ID). The aim of this study was to identify existing indicators for
medical DS care, by reviewing the literature. METHODS: We systematically searched
six databases (PubMed, EMBASE, Web of Science, CINAHL, PsycINFO, Google Scholar)
for studies concerning the development and implementation of quality indicators
for DS and/or ID care, published until February 1st 2015. The scoping review
method was used, including systematic data extraction and stakeholder
consultation. RESULTS: We identified 13 studies concerning quality indicators for
ID care that obtained data originating from questionnaires
(patient/family/staff), medical files and/or national databases. We did not find
any indicator sets specifically for DS care. Consulted stakeholders did not come
up with additional indicator sets. Existing indicators for ID care predominantly
focus on support services. Indicators in care for people with ID targeting
medical care are scarce. Of the 70 indicators within the 13 indicator sets, 10%
are structure indicators, 34% process, 32% outcome and 24% mixed. Ten of the 13
sets include indicators on the WHO quality dimensions 'patient-centeredness',
'effectiveness' and 'efficiency' of care. 'Accessibility' is covered by nine
sets, 'equitability' by six, and 'safety' by four. Most studies developed
indicators in a multidisciplinary manner in a joint effort with all relevant
stakeholders; some used focus groups to include people with ID. CONCLUSION: To
our knowledge, this is the first review that searched for studies on quality
indicators in DS care. Hence, the study contributes to existing knowledge on DS
care as well as on measuring quality of care. Future research should address the
development of a compact set of quality indicators for the DS care chain as a
whole. Indicators should preferably be patient-centred and outcome-oriented,
including user perspectives, while developed in a multidisciplinary way to
achieve successful implementation.
PMID- 28420358
TI - Healthcare utilization in older patients using personal emergency response
systems: an analysis of electronic health records and medical alert data : Brief
Description: A Longitudinal Retrospective Analyses of healthcare utilization
rates in older patients using Personal Emergency Response Systems from 2011 to
2015.
AB - BACKGROUND: Personal Emergency Response Systems (PERS) are traditionally used as
fall alert systems for older adults, a population that contributes an
overwhelming proportion of healthcare costs in the United States. Previous
studies focused mainly on qualitative evaluations of PERS without a longitudinal
quantitative evaluation of healthcare utilization in users. To address this gap
and better understand the needs of older patients on PERS, we analyzed
longitudinal healthcare utilization trends in patients using PERS through the
home care management service of a large healthcare organization. METHODS:
Retrospective, longitudinal analyses of healthcare and PERS utilization records
of older patients over a 5-years period from 2011-2015. The primary outcome was
to characterize the healthcare utilization of PERS patients. This outcome was
assessed by 30-, 90-, and 180-day readmission rates, frequency of principal
admitting diagnoses, and prevalence of conditions leading to potentially
avoidable admissions based on Centers for Medicare and Medicaid Services
classification criteria. RESULTS: The overall 30-day readmission rate was 14.2%,
90-days readmission rate was 34.4%, and 180-days readmission rate was 42.2%.
While 30-day readmission rates did not increase significantly (p = 0.16) over the
study period, 90-days (p = 0.03) and 180-days (p = 0.04) readmission rates did
increase significantly. The top 5 most frequent principal diagnoses for inpatient
admissions included congestive heart failure (5.7%), chronic obstructive
pulmonary disease (4.6%), dysrhythmias (4.3%), septicemia (4.1%), and pneumonia
(4.1%). Additionally, 21% of all admissions were due to conditions leading to
potentially avoidable admissions in either institutional or non-institutional
settings (16% in institutional settings only). CONCLUSIONS: Chronic medical
conditions account for the majority of healthcare utilization in older patients
using PERS. Results suggest that PERS data combined with electronic medical
records data can provide useful insights that can be used to improve health
outcomes in older patients.
PMID- 28420359
TI - Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation
and oxidative stress: a proteomic study.
AB - BACKGROUND: Radix Bupleuri (RB) has been popularly used for treating many liver
diseases such as chronic hepatic inflammation and viral Hepatitis in China.
Increasing clinical and experimental evidence indicates the potential
hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS)
have been identified as major bioactive compounds isolated from RB, which may be
also responsible for RB-induced liver injury. METHODS: Serum AST, ALT and LDH
levels were determined to evaluate SS-induced liver injury in mice. Serum and
liver total triglyceride and cholesterol were used to indicate lipid metabolism
homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative
stress level after SS administration. Western blot was used to detect CYP2E1
expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was
applied to analyze the protein expression profiles in livers of mice administered
with different doses of SS for different time periods. Gene ontology analysis,
cluster and enrichment analysis were employed to elucidate potential mechanism
involved. HepG2 cells were used to identify our findings in vitro. RESULTS: SS
dose- and time-dependently induced liver injury in mice, indicated by increased
serum AST, ALT and LDH levels. According to proteomic analysis, 487
differentially expressed proteins were identified in mice administrated with
different dose of SS for different time periods. Altered proteins were enriched
in pathways such as lipid metabolism, protein metabolism, macro molecular
transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1
expression in a time and dose dependent manner, and induced oxidative stress both
in vivo and in vitro. CONCLUSION: Our results identified hepatotoxicity and
established dose-time course-liver toxicity relationship in mice model of SS
administration and suggested potential mechanisms, including impaired lipid and
protein metabolism and oxidative stress. The current study provides experimental
evidence for clinical safe use of RB, and also new insights into understanding
the mechanism by which SS and RB induced liver injury.
PMID- 28420360
TI - Operative versus conservative treatment of apophyseal avulsion fractures of the
pelvis in the adolescents: a systematical review with meta-analysis of clinical
outcome and return to sports.
AB - BACKGROUND: Avulsion fractures of the pelvic apophyses typically occur in
adolescent athletes due to a sudden strong muscle contraction while growth plates
are still open. The main goals of this systematic review with meta-analysis were
to summarize the evidence on clinical outcome and determine the rate of return to
sports after conservative versus operative treatment of avulsion fractures of the
pelvis. METHODS: A systematic search of the Ovid database was performed in
December 2016 to identify all published articles reporting outcome and return to
preinjury sport-level after conservative or operative treatment of avulsion
fractures of the pelvis in adolescent patients. Included studies were abstracted
regarding study characteristics, patient demographics and outcome measures. The
methodological quality of the studies was assessed with the Coleman Methodology
Score (CMS). RESULTS: Fourteen studies with a total of 596 patients met the
inclusion criteria. The mean patient age was 14.3 +/- 0.6 years and 75.5% of
patients were male. Affected were the anterior inferior iliac spine (33.2%),
ischial tuberosity (29.7%), anterior superior iliac spine (27.9%), iliac crest
(6.7%) lesser trochanter (1.8%) and superior corner of the pubic symphysis
(1.2%). Mean follow-up was 12.4 +/- 11.7 months and most of the patients
underwent a conservative treatment (89.6%). The overall success rate was higher
in the patients receiving surgery (88%) compared to the patients receiving
conservative treatment (79%) (p = 0,09). The rate of return to sports was 80% in
conservative and 92% in operative treated patients (p = 0,03). Overall, the
methodological quality of the included studies was low, with a mean CMS of 41.2.
CONCLUSION: On the basis of the present meta-analysis, the overall success and
return to sports rate was higher in the patients receiving surgery. Especially in
patients with fragment displacement greater 15 mm and high functional demands,
surgical treatment should be considered.
PMID- 28420361
TI - Health care availability, quality, and unmet need: a comparison of transgender
and cisgender residents of Ontario, Canada.
AB - BACKGROUND: Evidence suggests that transgender (trans) individuals in Canada are
a medically underserved population; barriers range from lack of provider
knowledge on trans issues to refusal of care. This paper provides the first
formal estimation of health care inequalities between trans and cisgender
individuals in Ontario, Canada. METHODS: Weighted statistics from the Ontario
wide Trans PULSE Project (n = 433) were compared with age-standardized Ontario
data from the Canadian Community Health Survey (n = 39,980) to produce
standardized prevalence differences (SPDs). Analysis was also conducted
separately for trans men and trans women, each compared to the age-standardized
Ontario population. RESULTS: An estimated 33.2% (26.4,40.9) of trans Ontarians
reported a past-year unmet health care need in excess of the 10.7% expected based
on the age-standardized Ontario population. Inequality was greatest comparing
trans with cisgender men (SPD = 34.4% (23.0, 46.1). While trans Ontarians
evaluated health care availability in Ontario similarly to the broader
population, they were significantly more likely to evaluate availability in their
community as fair or poor. CONCLUSIONS: Trans Ontarians experience inequalities
in perception and reported experiences of health care access, with 43.9%
reporting a past-year unmet health care need.
PMID- 28420362
TI - Clinical, hemispheric, and autonomic changes associated with use of closed-loop,
allostatic neurotechnology by a case series of individuals with self-reported
symptoms of post-traumatic stress.
AB - BACKGROUND: The objective of this pilot study was to explore the use of a closed
loop, allostatic, acoustic stimulation neurotechnology for individuals with self
reported symptoms of post-traumatic stress, as a potential means to impact
symptomatology, temporal lobe high frequency asymmetry, heart rate variability
(HRV), and baroreflex sensitivity (BRS). METHODS: From a cohort of individuals
participating in a naturalistic study to evaluate use of allostatic
neurotechnology for diverse clinical conditions, a subset was identified who
reported high scores on the Posttraumatic Stress Disorder Checklist (PCL). The
intervention entailed a series of sessions wherein brain electrical activity was
monitored noninvasively at high spectral resolutions, with software algorithms
translating selected brain frequencies into acoustic stimuli (audible tones) that
were delivered back to the user in real time, to support auto-calibration of
neural oscillations. Participants completed symptom inventories before and after
the intervention, and a subset underwent short-term blood pressure recordings for
HRV and BRS. Changes in temporal lobe high frequency asymmetry were analyzed from
baseline assessment through the first four sessions, and for the last four
sessions. RESULTS: Nineteen individuals (mean age 47, 11 women) were enrolled,
and the majority also reported symptom scores that exceeded inventory thresholds
for depression. They undertook a median of 16 sessions over 16.5 days, and 18
completed the number of sessions recommended. After the intervention, 89% of the
completers reported clinically significant decreases in post-traumatic stress
symptoms, indicated by a change of at least 10 points on the PCL. At a group
level, individuals with either rightward (n = 7) or leftward (n = 7) dominant
baseline asymmetry in temporal lobe high frequency (23-36 Hz) activity
demonstrated statistically significant reductions in their asymmetry scores over
the course of their first four sessions. For 12 individuals who underwent short
term blood pressure recordings, there were statistically significant increases in
HRV in the time domain and BRS (Sequence Up). There were no adverse events.
CONCLUSION: Closed-loop, allostatic neurotechnology for auto-calibration of
neural oscillations appears promising as an innovative therapeutic strategy for
individuals with symptoms of post-traumatic stress. TRIALS REGISTRATION:
ClinicalTrials.gov #NCT02709369 , retrospectively registered on March 4, 2016.
PMID- 28420363
TI - Context matters! sources of variability in weekend physical activity among
families: a repeated measures study.
AB - BACKGROUND: Family involvement is an essential component of effective physical
activity (PA) interventions in children. However, little is known about the PA
levels and characteristics of PA among families. This study used a repeated
measures design and multiple data sources to explore the variability and
characteristics of weekend PA among families. METHODS: Families (including a
'target' child aged 9-11 years, their primary caregiver(s) and siblings aged 6-8
years) were recruited through primary schools in Liverpool, UK. Participants
completed a paper-based PA diary and wore an ActiGraph GT9X accelerometer on
their left wrist for up to 16 weekend days. ActiGraph.csv files were analysed
using the R-package GGIR version 1.1-4. Mean minutes of moderate-to-vigorous PA
(MVPA) for each weekend of measurement were calculated using linear mixed models,
and variance components were estimated for participant (inter-individual),
weekend of measurement, and residual error (intra-individual). Intraclass
correlation coefficients (ICC) were calculated from the proportion of total
variance accounted for by inter-individual sources, and used as a measure of
reliability. Diary responses were summed to produce frequency counts. To offer
contextual insight into weekend PA among family units, demographic,
accelerometer, and diary data were combined to form two case studies
representative of low and high active families. RESULTS: Twenty-five participants
from 7 families participated, including 7 'target' children (mean age 9.3 +/- 1.1
years, 4 boys), 6 siblings (mean age 7.2 +/- 0.7 years; 4 boys) and 12 adults (7
mothers and 5 fathers). There was a high degree of variability in target
children's (ICC = 0.55), siblings (ICC = 0.38), and mothers' MVPA (ICC = 0.58),
but not in fathers' MVPA (ICC = 0.83). Children's weekend PA was mostly
unstructured in nature and undertaken with friends, whereas a greater proportion
of parents' weekend PA was undertaken alone in structured settings. The family
case studies demonstrated that in the selected cases MVPA levels and variability
across weekends were contingent on mode of PA participation. CONCLUSIONS: These
novel findings enhance understanding of the variability and characteristics of
weekend PA among family units. The study demonstrates the utility of PA diaries
in conjunction with accelerometers to provide understanding of the mode and
contexts of out-of-school and family-based PA.
PMID- 28420364
TI - Anterior inferior plating versus superior plating for clavicle fracture: a meta
analysis.
AB - BACKGROUND: The position of plate fixation for clavicle fracture remains
controversial. Our objective was to perform a comprehensive review of the
literature and quantify the surgical parameters and clinical indexes between the
anterior inferior plating and superior plating for clavicle fracture. METHODS:
PubMed, EMBASE, and the Cochrane Library were searched for randomized and non
randomized studies that compared the anterior inferior plating with the superior
plating for clavicle fracture. The relative risk or standardized mean difference
with 95% confidence interval was calculated using either a fixed- or random
effects model. RESULTS: Four randomized controlled trials and eight observational
studies were identified to compare the surgical parameters and clinical indexes.
For the surgical parameters, the anterior inferior plating group was better than
the superior plating group in operation time and blood loss (P < 0.05).
Furthermore, in terms of clinical indexes, the anterior inferior plating was
superior to the superior plating in reducing the union time, and the two kinds of
plate fixation methods were comparable in constant score, and the rate of
infection, nonunion, and complications (P > 0.05). CONCLUSIONS: Based on the
current evidence, the anterior inferior plating may reduce the blood loss, the
operation and union time, but no differences were observed in constant score, and
the rate of infection, nonunion, and complications between the two groups. Given
that some of the studies have low quality, more randomized controlled trails with
high quality should be conduct to further verify the findings.
PMID- 28420365
TI - Social determinants of antibiotic misuse: a qualitative study of community
members in Haryana, India.
AB - BACKGROUND: Antibiotic resistance is a global public health crisis. In India
alone, multi-drug resistant organisms are responsible for over 58,000 infant
deaths each year. A major driver of drug resistance is antibiotic misuse, which
is a pervasive phenomenon worldwide. Due to a shortage of trained doctors, access
to licensed allopathic doctors is limited in India's villages. Pharmacists and
unlicensed medical providers are commonly the primary sources of healthcare.
Patients themselves are also key participants in the decision to treat an illness
with antibiotics. Thus, better understanding of the patient-provider interactions
that may contribute to patients' inappropriate use of antibiotics is critical to
reducing these practices in urban and rural Indian villages. METHODS: We
conducted a qualitative study of the social determinants of antibiotic use among
twenty community members in Haryana, India. Semi-structured interview questions
focused on two domains: typical antibiotic use and the motivation behind these
practices. A cross-sectional pilot survey investigated the same twenty
participants' understanding and usage of antibiotics. Interview and open-ended
survey responses were translated, transcribed, and coded for themes. RESULTS:
Antibiotics and the implications of their misuse were poorly understood by study
participants. No participant was able to correctly define the term antibiotics.
Participants with limited access to an allopathic doctor, either for logistic or
economic reasons, were more likely to purchase medications directly from a
pharmacy without a prescription. Low income participants were also more likely to
prematurely stop antibiotics after symptoms subsided. Regardless of income,
participants were more likely to seek an allopathic doctor for their children
than for themselves. CONCLUSIONS: The prevalent misuse of antibiotics among these
community members reinforces the importance of conducting research to develop
effective strategies for stemming the tide of antibiotic resistance in India's
villages.
PMID- 28420366
TI - Pirfenidone attenuates bleomycin-induced pulmonary fibrosis in mice by regulating
Nrf2/Bach1 equilibrium.
AB - BACKGROUND: Oxidative stress is one of the important factors involved in the
pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear
factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric
a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the
expression level of antioxidant factors, further regulating the function of
oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for
IPF therapy approved drugs. PFD regulates intracellular antioxidants, inhibits
secretion of inflammatory cytokines and collagen synthesis. However the
mechanisms of its antioxidant effects remain elusive. METHODS: Effects of PFD
treatment were studied in mouse lung fibroblasts (MLF) following induction by
transforming-growth factor beta 1 (TGF-beta1) and in mice following bleomycin
induced lung fibrosis. The mRNA and protein levels of oxidative stress-related
factors Nrf2/Bach1 and their downstream antioxidant factors heme oxygenase-1 (Ho
1) and glutathione peroxidase 1 (Gpx1) were determined by RT-PCR and Western
blot. Fibrosis-related cytokines interleukin-6 (IL-6) and myofibroblast markers
type 1 collagen alpha1 (COL1A1) levels in supernate of MLF, serum, and
bronchoalveolar lavage fluid (BALF) as well as malondialdehyde (MDA) in serum and
BALF were detected by ELISA, reactive oxygen species (ROS) generation was
measured by 2',7'- dichlorofluorescin diacetate (DCFH-DA) assay and lung
pathological/morphological alterations in mice were observed by HE and Masson to
assess the antioxidant mechanism and therapeutic effects on pulmonary fibrosis
induced by bleomycin. RESULTS: PFD inhibited Bach1 mRNA and protein expressions
in mouse lung fibroblasts induced by TGF-beta1 and lung tissues with pulmonary
fibrosis induced by bleomycin. Furthermore, it improved Nrf2, Ho-1 and Gpx1 mRNA
and protein expressions. After PFD treatment, COL1A1and IL-6 levels in supernate
of MLF, serum, and BALF as well as ROS in lung tissues and MDA in serum and BALF
from a mouse with pulmonary fibrosis were significantly decreased, and the
infiltration of lung inflammatory cells and fibrosis degree were alleviated.
CONCLUSIONS: Theraputic effects of PFD for IPF were involved in Nrf2/Bach1
equilibrium which regulated the capacity of oxidative stress. The study provided
new insights into the antioxidant mechanism of PFD.
PMID- 28420367
TI - Rationale and methods of the iFightDepression study: A double-blind, randomized
controlled trial evaluating the efficacy of an internet-based self-management
tool for moderate to mild depression.
AB - BACKGROUND: During the last decade online interventions have emerged as a
promising approach for patients with mild/moderate depressive symptoms, reaching
at large populations and representing cost-effective alternatives. The main
objective of this double-blind, randomized controlled trial is to examine the
efficacy of an internet-based self-management tool (iFightDepression) for mild to
moderate depression as an add-on to treatment as usual (TAU) versus internet
based psychoeducation plus TAU. METHODS: A total of 310 participants with major
depression disorder (MDD) will be recruited at four different mental-health
facilities in Spain. Participants will be randomly allocated to one of two study
arms: iFightDepression (iFD) tool + TAU vs. internet-based psychoeducation + TAU.
Both interventions last for 8 weeks and there is a 12 weeks follow up. The
primary outcome measure is changes in depressive symptoms assessed with the
Hamilton Depression Rating Scale. Additionally, pre-post interventions
assessments will include socio-demographic data, a brief medical and clinical
history and self-reported measures of depressive symptoms, quality of life,
functional impairments and satisfaction with the iFD tool. DISCUSSION:
iFightDepression is an easy-prescribed tool that could increase the efficacy of
conventional treatment and potentially reach untreated patients, shortening
waiting lists to receive psychological treatment. Confirming the efficacy of the
iFD internet-based self-management tool as an add-on treatment for individuals
with mild to moderate depression will be clinically-relevant. TRIAL REGISTRATION:
Registration number NCT02312583 . Clinicaltrials.gov . December 4, 2014.
PMID- 28420368
TI - Outcomes following percutaneous coronary revascularization among South Asian and
Chinese Canadians.
AB - BACKGROUND: Previous data suggest significant ethnic differences in outcomes
following percutaneous coronary revascularization (PCI), though previous studies
have focused on subgroups of PCI patients or used administrative data only. We
sought to compare outcomes in a population-based cohort of men and women of South
Asian (SA), Chinese and "Other" ethnicity. METHODS: Using a population-based
registry, we identified 41,792 patients who underwent first revascularization via
PCI in British Columbia, Canada, between 2001 and 2010. We defined three ethnic
groups (SA, 3904 [9.3%]; Chinese, 1345 [3.2%]; and all "Others" 36,543 [87.4%]).
Differences in mortality, repeat revascularization (RRV) and target vessel
revascularization (TVR), at 30 days and from 31 days to 2 years were examined.
RESULTS: Adjusted mortality from 31 days to 2 years was lower in Chinese patients
than in "Others" (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.53
0.97), but not different between SAs and "Others". SA patients had higher RRV at
30 days (adjusted odds ratio [OR] 1.30; 95% CI: 1.12-1.51) and from 31 days to 2
years (adjusted hazard ratio [HR] 1.17; 95% CI: 1.06-1.30) compared to "Others".
In contrast, Chinese patients had a lower rate of RRV from 31 days to 2 years
(adjusted HR 0.79; 95% CI: 0.64-0.96) versus "Others". SA patients also had
higher rates of TVR at 30 days (adjusted OR 1.35; 95% CI: 1.10-1.66) and from 31
days to 2 years (adjusted HR 1.19; 95% CI: 1.06-1.34) compared to "Others".
Chinese patients had a lower rate of TVR from 31 days to 2 years (adjusted HR
0.76; 95% CI: 0.60-0.96). CONCLUSIONS: SA had higher RRV and TVR rates while
Chinese Canadians had lower rates of long-term RRV, compared to those of "Other"
ethnicity. Further research to elucidate the reasons for these differences could
inform targeted strategies to improve outcomes.
PMID- 28420369
TI - Improving the effectiveness of sickness benefit case management through a public
private partnership? A difference-in-difference analysis in eighteen Danish
municipalities.
AB - BACKGROUND: The aim of this study was to investigate whether a multidimensional
public-private partnership intervention, focussing on improving the quality and
efficiency of sickness benefit case management, reduced the sickness benefit
duration and the duration until self-support. METHODS: We used a difference-in
difference (DID) design with six intervention municipalities and 12 matched
control municipalities in Denmark. The study sample comprised 282,103 sickness
benefit spells exceeding four weeks. The intervention group with 110,291 spells
received the intervention, and the control group with 171,812 spells received
ordinary sickness benefit case management. Using register data, we fitted Cox
proportional hazard ratio models, estimating hazard ratios (HR) and confidence
intervals (CI). RESULTS: We found no joint effect of the intervention on the
sickness benefit duration (HR 1.02, CI 0.97-1.07) or the duration until self
support (HR 0.99, CI 0.96-1.02). The effect varied among the six municipalities,
with sickness benefit HRs ranging from 0.96 (CI 0.93-1.00) to 1.13 (CI 1.08-1.18)
and self-support HRs ranging from 0.91 (CI 0.82-1.00) to 1.11 (CI 1.06-1.17).
CONCLUSIONS: Compared to receiving ordinary sickness benefit management the
intervention had on average no effect on the sickness benefit duration or
duration until self-support. However, the effect varied considerably among the
six municipalities possibly due to differences in the implementation or the
complexity of the intervention.
PMID- 28420370
TI - Neuroprotective effect of Demethoxycurcumin, a natural derivative of Curcumin on
rotenone induced neurotoxicity in SH-SY 5Y Neuroblastoma cells.
AB - BACKGROUND: Mitochondrial dysfunction and oxidative stress are the main toxic
events leading to dopaminergic neuronal death in Parkinson's disease (PD) and
identified as vital objective for therapeutic intercession. This study
investigated the neuro-protective effects of the demethoxycurcumin (DMC), a
derivative of curcumin against rotenone induced neurotoxicity. METHODS: SH-SY5Y
neuroblastoma cells are divided into four experimental groups: untreated cells,
cells incubated with rotenone (100 nM), cells treated with DMC (50 nM) + rotenone
(100 nM) and DMC alone treated. 24 h after treatment with rotenone and 28 h after
treatment with DMC, cell viability was assessed using the MTT assay, and levels
of ROS and MMP, plus expression of apoptotic protein were analysed. RESULTS:
Rotenone induced cell death in SH-SY5Y cells was significantly reduced by DMC
pretreatment in a dose-dependent manner, indicating the potent neuroprotective
effects of DMC. Rotenone treatment significantly increases the levels of ROS,
loss of MMP, release of Cyt-c and expression of pro-apoptotic markers and
decreases the expression of anti-apoptotic markers. CONCLUSIONS: Even though the
results of the present study indicated that the DMC may serve as a potent
therapeutic agent particularly for the treatment of neurodegenerative diseases
like PD, further pre-clinical and clinical studies are required.
PMID- 28420371
TI - Effect of pulmonary arteriovenous malformations on the mechanical properties of
the lungs.
AB - BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are present in
approximately 15-50% individuals with hereditary hemorrhagic telangiectasia
(HHT). They may be isolated but more often are multiple. The goal of this study
was to evaluate the influence of PAVMs on lung mechanical properties. METHODS: We
reviewed the files of all adult patients (age >= 18 years) referred to our Center
for evaluation of HHT between 2005 and 2013. The diagnosis of HHT was based on
the Curacao criteria and/or the presence of a pathogenic mutation. Exclusion
criteria included: chronic cardiac or lung disease (i.e. asthma or COPD),
suspicion of pulmonary hypertension on echocardiography, current or past smoking
(>10 pack-years), history of thoracic surgery, previous treatment of PAVMs by
embolotherapy, lung infection or thromboembolic disease in the past 3 months,
pregnancy and obesity (BMI > 30 kg/m2). Chest high resolution CT-scan and
pulmonary function tests were performed the same day in all patients as part of
our routine work-up. RESULTS: One hundred and fifty five patients with HHT were
included (age: 44.4 +/- 16.7 yrs - mean +/- SD -; males: 39%). Eighty eight
patients had no PAVM, 45 had 1-3 PAVMS and 22 had at least 4 PAVMs. Thirty eight
patients had unilateral PAVMs and 29 bilateral PAVMs. We found no statistical
relationship between the number, the size and the laterality of PAVMs and results
of lung flows and volumes. CONCLUSION: We found no evidence that PAVMs have a
significant influence on lung mechanical properties as measured using routine
pulmonary function tests in adult patients with HHT, even in case of numerous,
macroscopic or bilateral malformations.
PMID- 28420372
TI - Erratum to: Trends in HIV counseling and testing uptake among married individuals
in Rakai, Uganda.
PMID- 28420373
TI - Early outbreak detection by linking health advice line calls to water
distribution areas retrospectively demonstrated in a large waterborne outbreak of
cryptosporidiosis in Sweden.
AB - BACKGROUND: In the winter and spring of 2011 a large outbreak of
cryptosporidiosis occurred in Skelleftea municipality, Sweden. This study
summarizes the outbreak investigation in terms of outbreak size, duration,
clinical characteristics, possible source(s) and the potential for earlier
detection using calls to a health advice line. METHODS: The investigation
included two epidemiological questionnaires and microbial analysis of samples
from patients, water and other environmental sources. In addition, a
retrospective study based on phone calls to a health advice line was performed by
comparing patterns of phone calls between different water distribution areas.
RESULTS: Our analyses showed that approximately 18,500 individuals were affected
by a waterborne outbreak of cryptosporidiosis in Skelleftea in 2011. This makes
it the second largest outbreak of cryptosporidiosis in Europe to date.
Cryptosporidium hominis oocysts of subtype IbA10G2 were found in patient and
sewage samples, but not in raw water or in drinking water, and the initial
contamination source could not be determined. The outbreak went unnoticed to
authorities for several months. The analysis of the calls to the health advice
line provides strong indications early in the outbreak that it was linked to a
particular water treatment plant. CONCLUSIONS: We conclude that an earlier
detection of the outbreak by linking calls to a health advice line to water
distribution areas could have limited the outbreak substantially.
PMID- 28420374
TI - Prevalence and associated factors of common mental disorders among Ethiopian
migrant returnees from the Middle East and South Africa.
AB - BACKGROUND: Ethiopian migrants to the Middle East and South Africa experience a
range of problems at various stages of their migration including overwork, sleep
deprivation, denial of food, emotional abuse, difficulty adapting to the host
culture, salary denial, sexual abuse, labor exploitation, confiscation of their
travel documents, confinement, denial of medication, lack of access to legal
service and degrading attitude by employers, traffickers and smugglers. These
experiences can be associated with different types of mental disorders. This
study sought to determine the prevalence of common mental disorders (CMD) and
socio-demographic and other migration related associated factors among Ethiopian
migrant returnees from the Middle East and South Africa. METHOD: A cross
sectional study was conducted using non-probability (i.e. purposive, availability
and snowball) sampling techniques. Migrant returnees (n = 1036) were contacted
individually at their homes in eight high prevalent immigrant returnee locations
in Ethiopia. Common mental disorders were assessed using the self-reporting
questionnaire (SRQ-20) and a structured questionnaire was employed to collect
data on socio-demographic and migration related characteristics. Data were
analyzed using descriptive statistics, univariate logistic regression, and
multivariable logistic regression. RESULTS: The prevalence of CMD among migrant
returnees was found to be 27.6%. Highly prevalent specific CMD symptoms included
headaches, poor appetite, being tired, sleeping problems, and feeling unhappy or
nervous. Being originally from Amhara and Oromia regions, being Christian, being
divorced, not receiving salary on time, not being able to contact family, unable
to prepare for domestic labor abroad, lack of cross- cultural awareness, and lack
of knowledge and skills for work were all important risk factors for CMD.
Migrants experienced adversities at different stages of their migration which are
associated with psychological distress and even to long term mental illnesses.
CONCLUSIONS: CMD symptoms were found to be prevalent among Ethiopian migrant
returnees. As pre-migration factors are associated with CMD symptoms, pre
departure training could be useful to mitigate the risk factors. Creating and
routinely arranging mental health interventions and rehabilitation services are
advisable for returnees who are screened for, or diagnosed with, mental health
problems.
PMID- 28420375
TI - Silent progression in patients with rheumatoid arthritis: is DAS28 remission an
insufficient goal in RA? Results from the German Remission-plus cohort.
AB - BACKGROUND: Remission is arguably the ultimate therapeutic goal in rheumatoid
arthritis (RA). Applying modern strategies, clinical remission can be achieved in
a substantial number of patients with early RA (ERA). Even in those patients, the
number and scope of erosions can increase. We, therefore, investigated the value
of MRI for the detection of radiological progression in patients with DAS28
improvement and/or clinical remission of the German Remission-plus cohort.
METHODS: Data-sets of 80 RA patients (according to 2010 ACR/EULAR criteria) from
the Remission-plus study cohort, who fulfilled the following criteria, were
retrospectively analysed: availability of two consecutive MRI scans (low-field
MRI, follow-up interval 1 year) of the clinically dominant hand and wrist, and
the presence of DAS28 (CRP) scores at both time points, which was used to assess
disease activity. RESULTS: Seventy-one of the 80 investigated patients presented
a numerical improvement of the DAS28 (CRP) after 12 months (DAS28(CRP) T0 average
(O) 4.96, SD 1.2; DAS28 T4 (12 month) O 2.6, SD 1.0), 73% of them also improved
in the RAMRIS-Score, while 24% demonstrated an increase despite DAS28 improvement
and 3% showed equal values. 48% of patients who improved in the DAS28 reached
EULAR remission. 41% of these patients had an increase in the RAMRIS Erosion
subscore after 12 months. When considering EULAR response criteria (non-response
(n = 7), moderate response (n = 19), good response (n = 45)), an increase of
erosions was found in 71.4% of non-responders, 52.6% of moderate responders, and
31.1% of good responders after 12 months, all compared to baseline. CONCLUSION:
Up to 40% of patients in this study demonstrated a progressive erosive disease
detected by MRI despite DAS28 improvement or EULAR remission. Future studies are
needed to determine the prognostic clinical impact of disease progression in MRI
despite clinical remission, and to investigate if DAS28 remission may be an
insufficient therapeutic goal and should be accompanied by MRI remission
criteria.
PMID- 28420376
TI - Workflow standardization of a novel team care model to improve chronic care: a
quasi-experimental study.
AB - BACKGROUND: Team-based chronic care models have not been widely adopted in
community settings, partly due to their varying effectiveness in randomized
control trials, implementation challenges, and concerns about physician
acceptance. The Palo Alto Medical Foundation designed and implemented "Champion,"
a novel team-based model that includes new standard work (e.g. proactive patient
outreach, pre-visit schedule grooming, depression screening, care planning,
health coaching) to support patients' self-management of hypertension and
diabetes. We investigated whether Champion improved clinical outcomes. METHODS:
We conducted a quasi-experimental study comparing the Champion clinic-level
intervention (n = 38 physicians) with a usual care clinic (n = 37 physicians) in
Northern California. The primary outcomes, blood pressure and glycohemoglobin
(A1c), were analyzed using a piecewise linear growth curve model for patients
exposed to a Champion physician visit (n = 3156) or usual care visit (n = 8034)
in the two years prior and one year post implementation. Secondary outcomes were
provider experience, compared at baseline and 12 months in both the intervention
and usual care clinics using multi-level ordered logistic modeling, and
electronic health record based fidelity measures. RESULTS: Compared to usual
care, in the first 6 months after a Champion physician visit, diabetes patients
aged 18-75 experienced an additional -1.13 mm Hg (95% CI: -2.23 to -0.04) decline
in diastolic blood pressure and -0.47 (95% CI: -0.61 to -0.33) decline in A1c.
There were no additional improvements in blood pressure or A1c 6 to 12 months
post physician visit. At 12 months, Champion physicians reported improved
experience with managing chronic care patients in 6 of 7 survey items (p < 0.05),
but compared to usual, this difference was only statistically significant for one
item (p < 0.05). Fidelity to standard work was uneven; depression screening was
the most commonly documented element (85% of patients), while care plans were the
least (30.8% of patients). CONCLUSIONS: Champion standard work improved glycemic
control over the first 6 months and physicians' experience with managing chronic
care; changes in blood pressure were not clinically meaningful. Our results
suggest the need to understand the relationship between the intervention, the
contextual features of implementation, and fidelity to further improve chronic
disease outcomes. This study was retrospectively registered with the ISRCTN
Registry on March 15, 2017 (ISRCTN11341906).
PMID- 28420377
TI - The association between child maltreatment and emotional, cognitive, and physical
health functioning in Vietnam.
AB - BACKGROUND: There is a paucity of research on correlates of child maltreatment in
limited-resource countries with a relatively high tolerance of harsh discipline.
This Vietnamese study aimed to investigate associations between different types
of child maltreatment and child emotional, cognitive, and physical health
functioning as well as moderation effects of gender and ethnicity. METHODS: This
cross-sectional study was conducted with 1851 randomly selected students aged 12
17 years. Both self-report and more objective measures (weight, height, study
ranking, and a memory test) were used. RESULTS: All types of child maltreatment
were associated with emotional dysfunctioning. Life time and past year
experiences of physical abuse and life time experiences of sexual abuse and
neglect were related to poorer perceived physical health. The study did not find
associations between any type of child maltreatment and overweight or underweight
status. Regarding cognitive functioning, life time experience of sexual abuse and
neglect were related to poorer working memory performance. Noticeably, emotional
abuse was related to better academic performance, which might be an indication of
"tiger parenting" practice in Vietnam, implying academic performance stimulation
at the expense of emotional security. No significant moderation effects by gender
and ethnicity were found. CONCLUSION: Even in a culture in which harsh discipline
is normative, child maltreatment was related to negative aspects of child
wellbeing including emotional, cognitive, and physical health functioning.
Efficient and low-cost interventions on child maltreatment should be developed
and conducted in Vietnam as well as other countries with similar contexts.
PMID- 28420378
TI - A cross-sectional survey assessing factors associated with reading cancer
screening information: previous screening behaviour, demographics and decision
making style.
AB - BACKGROUND: There is broad agreement that cancer screening invitees should know
the risks and benefits of testing before deciding whether to participate. In
organised screening programmes, a primary method of relaying this information is
via leaflets provided at the time of invitation. Little is known about why
individuals do not engage with this information. This study assessed factors
associated with reading information leaflets provided by the three cancer
screening programmes in England. METHODS: A cross-sectional survey asked
screening-eligible members of the general population in England about the
following predictor variables: uptake of previous screening invitations,
demographic characteristics, and 'decision-making styles' (i.e. the extent to
which participants tended to make decisions in a way that was avoidant, rational,
intuitive, spontaneous, or dependent). The primary outcome measures were the
amount of the leaflet that participants reported having read at their most recent
invitation, for any of the three programmes for which they were eligible.
Associations between these outcomes and predictor variables were assessed using
binary or ordinal logistic regression. RESULTS: After exclusions, data from 275,
309, and 556 participants were analysed in relation to the breast, cervical, and
bowel screening programmes, respectively. Notable relationships included
associations between regularity of screening uptake and reading (more of) the
information leaflets for all programmes (e.g. odds ratio: 0.16 for participants
who never/very rarely attended breast screening vs. those who always attended
previously; p = .009). Higher rational decision-making scores were associated
with reading more of the cervical and bowel screening leaflets (OR: 1.13, p <
.0005 and OR: 1.11, p = .045, respectively). Information engagement was also
higher for White British participants compared with other ethnic groups for
breast (OR: 3.28, p = .008) and bowel (OR: 2.58, p = .015) information; an
opposite relationship was observed for older participants (OR: 0.96, p = .048;
OR: 0.92, p = .029). CONCLUSIONS: Interventions that increase screening uptake
may also increase subsequent engagement with information. Future research could
investigate how to improve engagement at initial invitations. There may also be
scope to reduce barriers to accessing non-English information and alternative
communication strategies may benefit participants who are less inclined to weigh
up advantages and disadvantages as part of their decision-making.
PMID- 28420379
TI - Distribution and symmetrical patellofemoral pain patterns as revealed by high
resolution 3D body mapping: a cross-sectional study.
AB - BACKGROUND: Detailed pain mapping of extent and distribution in individuals with
patellofemoral pain (PFP) within and around a complex structure such as the knee
has yet to be explored. METHODS: Perceptions of on-going pain from adolescents
and young adults (N = 35) with long-standing (>10 months) PFP were collected on
high-resolution 3D digital body-schema of the knees. Location, area of pain, pain
intensity, laterality, worse side of knee pain, symptom duration, and symmetry in
bilateral knee pain were recorded. A threshold for naturally occurring variations
in symmetrical knee pain drawings were collected from 18 healthy controls and
used in combination with the development a symmetry index (0-1) to create a fuzzy
rule for classifying symmetrical and non-symmetrical PFP patterns as compared to
a PFP expert. The symmetry index was computed and tested using a correlation
coefficient alone or in combination with the Jaccard index and the true and false
positive rates (TPR and FPR, respectively) determined. RESULTS: The peripatellar
region was the common report of pain location however, novel and nonconforming
PFP patterns were identified and the majority of individuals (22 of 27) with
bilateral PFP expressed highly-symmetric mirror-image pain. Individuals with
symptom duration of 5 years or more had a greater area of pain, compared to those
with symptoms for less than 5 years. The total area of pain was correlated to
symptom duration for those with extended symptoms durations and a progression
towards an "O" shaped pattern emerged. A TPR of 100% for identifying symmetrical
knee pain patterns was found however the expert PFP tended to be stricter, as
reflected in FPR of 20%. CONCLUSIONS: A high proportion of PFP patterns or
symptoms occur in mirrored locations and are exceptionally symmetrical, and long
duration of symptoms appear to converge to an 'O' shape. Classifying symmetrical
pain patterns is subjective however simple fuzzy rules and correlations can be
used to increase objectivity. This study highlights a gap in knowledge of PFP
symptom presentation, reveals what may be a natural progression of symptoms, and
provides valuable clinical insight for both pain management and treatment.
PMID- 28420380
TI - Educational status as determinant of men's knowledge about vasectomy in Dangila
town administration, Amhara region, Northwest Ethiopia.
AB - BACKGROUND: Although vasectomy is effective and less expensive contraceptive
method, only few men are using it in Africa. The main reason for low level use
may be low knowledge about vasectomy among men. Only few studies tried to
investigate level of knowledge of vasectomy among married men in Ethiopia. But
these studies have limitations in measuring knowledge. This study was therefore
designed to assess knowledge of vasectomy among married men in Dangila town.
METHOD: A community based cross sectional study was conducted in Dangila town.
Sample size was calculated using OpenEPI online sample size calculator for
population based surveys. Multistage sampling technique was employed to recruit
the study participants. Data collectors interviewed selected men using structured
Amharic questionnaire from June to July, 2014. Two days training was given to
data collectors and supervisors. Data were entered and analyzed using SPSS
version 16. Binary logistic regression analysis was done to identify determinants
of knowledge about vasectomy. RESULT: A total of 872 men were interviewed. About
75% of men reported that they had ever heard about vasectomy. Men mentioned
friends as main source of information for vasectomy. Among those who had ever
heard, only 60.8% defined vasectomy correctly. About 20% defined vasectomy as "it
is making the man impotent." Similarly about 16% equated vasectomy with
castration. In this study, only 44.8% of men were knowledgeable about vasectomy.
Married men who completed secondary education were 4.10(95%CI; 2.48 - 6.75) times
more likely to be knowledgeable about vasectomy compared to those who did not
attend formal education. Those who attended above secondary education were
5.73(95%CI 3.76 - 8.73) times more likely to be knowledgeable about vasectomy
compared to those who did not attend formal education. CONCLUSION: Level of
knowledge about vasectomy among married men in Dangla town was low and
educational status was an important predictor of knowledge about vasectomy.
Efforts are needed to improve knowledge of men about vasectomy. In addition,
encouraging boys to complete secondary education may help improve knowledge of
men about vasectomy.
PMID- 28420381
TI - Operations research in global health: a scoping review with a focus on the themes
of health equity and impact.
AB - BACKGROUND: Operations research (OR) is a discipline that uses advanced
analytical methods (e.g. simulation, optimisation, decision analysis) to better
understand complex systems and aid in decision-making. Herein, we present a
scoping review of the use of OR to analyse issues in global health, with an
emphasis on health equity and research impact. A systematic search of five
databases was designed to identify relevant published literature. A global
overview of 1099 studies highlights the geographic distribution of OR and common
OR methods used. From this collection of literature, a narrative description of
the use of OR across four main application areas of global health - health
systems and operations, clinical medicine, public health and health innovation -
is also presented. The theme of health equity is then explored in detail through
a subset of 44 studies. Health equity is a critical element of global health that
cuts across all four application areas, and is an issue particularly amenable to
analysis through OR. Finally, we present seven select cases of OR analyses that
have been implemented or have influenced decision-making in global health policy
or practice. Based on these cases, we identify three key drivers for success in
bridging the gap between OR and global health policy, namely international
collaboration with stakeholders, use of contextually appropriate data, and varied
communication outlets for research findings. Such cases, however, represent a
very small proportion of the literature found. CONCLUSION: Poor availability of
representative and quality data, and a lack of collaboration between those who
develop OR models and stakeholders in the contexts where OR analyses are intended
to serve, were found to be common challenges for effective OR modelling in global
health.
PMID- 28420382
TI - Effect of tDCS stimulation of motor cortex and cerebellum on EEG classification
of motor imagery and sensorimotor band power.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a technique for
brain modulation that has potential to be used in motor neurorehabilitation.
Considering that the cerebellum and motor cortex exert influence on the motor
network, their stimulation could enhance motor functions, such as motor imagery,
and be utilized for brain-computer interfaces (BCIs) during motor
neurorehabilitation. METHODS: A new tDCS montage that influences cerebellum and
either right-hand or feet motor area is proposed and validated with a simulation
of electric field. The effect of current density (0, 0.02, 0.04 or 0.06 mA/cm2)
on electroencephalographic (EEG) classification into rest or right-hand/feet
motor imagery was evaluated on 5 healthy volunteers for different stimulation
modalities: 1) 10-minutes anodal tDCS before EEG acquisition over right-hand or
2) feet motor cortical area, and 3) 4-seconds anodal tDCS during EEG acquisition
either on right-hand or feet cortical areas before each time right-hand or feet
motor imagery is performed. For each subject and tDCS modality, analysis of
variance and Tukey-Kramer multiple comparisons tests (p <0.001) are used to
detect significant differences between classification accuracies that are
obtained with different current densities. For tDCS modalities that improved
accuracy, t-tests (p <0.05) are used to compare MU and beta band power when a
specific current density is provided against the case of supplying no
stimulation. RESULTS: The proposed montage improved the classification of right
hand motor imagery for 4 out of 5 subjects when the highest current was applied
for 10 minutes over the right-hand motor area. Although EEG band power changes
could not be related directly to classification improvement, tDCS appears to
affect variably different motor areas on MU and/or beta band. CONCLUSIONS: The
proposed montage seems capable of enhancing right-hand motor imagery detection
when the right-hand motor area is stimulated. Future research should be focused
on applying higher currents over the feet motor cortex, which is deeper in the
brain compared to the hand motor cortex, since it may allow observation of
effects due to tDCS. Also, strategies for improving analysis of EEG respect to
accuracy changes should be implemented.
PMID- 28420383
TI - PPBP and DEFA1/DEFA3 genes in hyperlipidaemia as feasible synergistic
inflammatory biomarkers for coronary heart disease.
AB - BACKGROUND: Coronary heart disease (CHD) is an important complication of
atherosclerosis. Biomarkers, which associate with CHD development, are potential
to predict CHD risk. To determine whether genes showing altered expression in
hyperlipidaemia (H) and coronary heart disease (CHD) patients compared with
controls could be CHD risk biomarkers. METHODS: Control, H, and CHD groups
represented atherosclerosis to CHD development. Gene profiling was investigated
in peripheral blood mononuclear cells using DNA microarrays. Eight selected genes
expressed only in H and CHD groups were validated by real-time quantitative
reverse transcription PCR and plasma protein determination. RESULTS: alpha
defensin (DEFA1/DEFA3), pro-platelet basic protein (PPBP), and beta and alpha2
hemoglobin mRNA expression was significantly increased in H and CHD groups
compared with controls, but only plasma PPBP and alpha-defensin proteins were
correspondingly increased. CONCLUSION: PPBP and DEFA1/DEFA3 could be potential
CHD biomarkers in Thai hyperlipidaemia patients.
PMID- 28420384
TI - Molecular characteristic of mcr-1 producing Escherichia coli in a Chinese
university hospital.
AB - BACKGROUND: Colistin has been considered as a last-line treatment option in
severe infections caused by multidrug-resistant (MDR) gram-negative pathogens.
However, the emergence of the mobile colistin resistance gene (mcr-1) has
challenged this viewpoint. The aim of this study is to explore the prevalence of
mcr-1 in Escherichia coli (E. coli) in a Chinese teaching hospital, and
investigate their molecular characteristics. METHODS: A total of 700 E. coli
isolates were used to screen mcr-1 by PCR and sequencing in a Chinese university
hospital from August 2014 to August 2015. Susceptibility test of mcr-1-producing
isolates was determined by Vitek -2 Compact system. 26 virulence factors (VFs),
phylogenetic groups, Multi-locus sequence typing (MLST), and DNA Fingerprinting
(ERIC-PCR) of strains were investigated by PCR. RESULTS: Four (0.6%) mcr-1
producing E. coli isolates were found in this study. The results of antibiotic
susceptibility test showed that all four isolates were resistant to colistin,
ciprofloxacin, levofloxacin, cefazolin, and trimethoprim/sulfamethoxazole, and
were susceptible to amikacin, ertapenem and imipenem. In addition, all 4 isolates
exhibited high-level resistance to aztreonam, cefotaxime and gentamicin. The
numbers of VFs contained in mcr-1 positive isolates were no more than 4 in our
study. MLST result demonstrated that these isolates were assigned to two sequence
types: ST156 and ST167. The result of phylogenetic analysis showed that four mcr
1-positive isolates belong to two phylogenetic groups: A and B1 group. ERIC-PCR
showed that four mcr-1 positive strains were categorized into three different
genotypes. CONCLUSIONS: Our study demonstrated a low prevalence of mcr-1 in E.
coli clinical isolates in a Chinese teaching hospital, and we have gained
insights into the molecular characteristics of these mcr-1-positive strains.
Increasing the surveillance of these infections, as well as taking effective
infection control measures are urgently needed to take to control the
transmission of mcr-1 gene.
PMID- 28420385
TI - Frontotemporal dementia as a comorbidity to idiopathic normal pressure
hydrocephalus (iNPH): a short review of literature and an unusual case.
AB - Behavioural variant frontotemporal dementia (bvFTD) and idiopathic normal
pressure hydrocephalus (iNPH) are neurodegenerative diseases that can present
with similar symptoms. These include decline in executive functions, psychomotor
slowness, and behavioural and personality changes. Ventricular enlargement is a
key radiological finding in iNPH that may also be present in bvFTD caused by the
C9ORF72 expansion mutation. Due to this, bvFTD has been hypothesized as a
potential comorbidity to iNPH but bvFTD patients have never been identified in
studies focusing in clinical comorbidities with iNPH. Here we describe a patient
with the C9ORF72 expansion-associated bvFTD who also showed enlarged ventricles
on brain imaging. The main clinical symptoms were severe gait disturbances and
psychiatric problems with mild cognitive decline. Cerebrospinal fluid removal
increased the patient's walking speed, so a ventriculoperitoneal shunt was
placed. After insertion of the shunt, there was a significant improvement in
walking speed as well as mild improvement in cognitive function but not in
neuropsychiatric symptoms relating to bvFTD. Comorbid iNPH should be considered
in bvFTD patients who have enlarged ventricles and severely impaired gait.
PMID- 28420386
TI - Sedation levels in dogs: a validation study.
AB - BACKGROUND: The aim of this study was to assess validation evidence for a
sedation scale for dogs. We hypothesized that the chosen sedation scale would be
unreliable when used by different raters and show poor discrimination between
sedation protocols. A sedation scale (range 0-21) was used to score 62 dogs
scheduled to receive sedation at two veterinary clinics in a prospective trial.
Scores recorded by a single observer were used to assess internal consistency and
construct validity of the scores. To assess inter-rater reliability, video
recordings of sedation assessment were randomized and blinded for viewing by 5
raters untrained in the scale. Videos were also edited to allow assessment of
inter-rater reliability of an abbreviated scale (range 0-12) by 5 different
raters. RESULTS: Both sedation scales exhibited excellent internal consistency
and very good inter-rater reliability (full scale, intraclass correlation
coefficient [ICCsingle] = 0.95; abbreviated scale, ICCsingle = 0.94). The full
scale discriminated between the most common protocols: dexmedetomidine
hydromorphone (median [range] of sedation score, 11 [1-18], n = 20) and
acepromazine-hydromorphone (5 [0-15], n = 36, p = 0.02). CONCLUSIONS: The
hypothesis was rejected. Full and abbreviated scales showed excellent internal
consistency and very good reliability between multiple untrained raters. The full
scale differentiated between levels of sedation.
PMID- 28420387
TI - Effects of host restriction factors and the HTLV-1 subtype on susceptibility to
HTLV-1-associated myelopathy/tropical spastic paraparesis.
AB - BACKGROUND: Although human T-lymphotropic virus type 1 (HTLV-1) infection is a
prerequisite for the development of HTLV-1-associated myelopathy/tropical spastic
paraparesis (HAM/TSP), specific provirus mutations in HAM/TSP have not yet been
reported. In this study, we examined whether HAM/TSP patients had the disease
specific genomic variants of HTLV-1 by analyzing entire sequences of HTLV-1
proviruses in these patients, including familial cases. In addition, we
investigated the genetic variants of host restriction factors conferring
antiretroviral activity to determine which mutations may be related to resistance
or susceptibility to HAM/TSP. RESULTS: The subjects included 30 patients with
familial HAM/TSP (f-HAM/TSP), 92 patients with sporadic HAM/TSP (s-HAM/TSP), and
89 asymptomatic HTLV-1 carriers (ACs). In all 211 samples, 37 samples (18%) were
classified into transcontinental subtype and 174 samples (82%) were classified as
Japanese subtype. Among three groups, the percentage of transcontinental subtype
in f-HAM/TSP, s-HAM/TSP and ACs was 33, 23 and 7%, respectively. The frequency of
transcontinental subtype was significantly higher in both f-HAM/TSP (p < 0.001)
and s-HAM/TSP (p < 0.001) than in ACs. Fifty mutations in HTLV-1 sequences were
significantly more frequent in HAM/TSP patients than in ACs, however, they were
common only in transcontinental subtype. Among these mutations, ten common
mutations causing amino acid changes in the HTLV-1 sequences were specific to the
transcontinental subtype. We examined host restriction factors, and detected a
rare variant in TRIM5alpha in HAM/TSP patients. The patients with TRIM5alpha 136Q
showed lower proviral loads (PVLs) than those with 136R (354 vs. 654 copies/104
PBMC, p = 0.003). The patients with the 304L variant of TRIM5alpha had
significantly higher PVLs than those with 304H (1669 vs. 595 copies/104 PBMC, p =
0.025). We could not find any HAM/TSP-specific mutations of host restriction
factors. CONCLUSIONS: Transcontinental subtype is susceptible to HAM/TSP,
especially in familial cases. Ten common mutations causing amino acid changes in
the HTLV-1 gene were specific to the transcontinental subtype. TRIM5alpha
polymorphisms were associated with PVLs, indicating that TRIM5alpha could be
implicated in HTLV-1 replication.
PMID- 28420388
TI - Association between maternal intake of n-6 to n-3 fatty acid ratio during
pregnancy and infant neurodevelopment at 6 months of age: results of the MOCEH
cohort study.
AB - BACKGROUND & AIMS: Long-chain polyunsaturated fatty acids (LC-PUFAs) are
essential for infant neurodevelopment. The nutritional adequacy of dietary LC
PUFAs depends not only on the LC-PUFAs intake but also on the n-6 to n-3 fatty
acid ratio (n-6/n-3 PUFAs). This study aimed to identify the association between
the maternal dietary n-6/n-3 PUFAs and motor and cognitive development of infants
at 6 months of age. METHODS: We used data from 960 participants in the Mothers
and Children's Environmental Health (MOCEH) study, which is a multi-center
prospective cohort study. Dietary intake of pregnant women was assessed by a one
day 24-h recall method. Food consumption of infants was estimated based on the
volume of breast milk and weaning foods. The duration of each feed was used to
estimate the likely volume of milk consumed. Dietary intake of infants at 6
months was also assessed by a 24-h recall method. Cognitive and motor development
of infants at 6 months of age was assessed by the Korean Bayley scales of infant
development edition II (BSID-II) including the mental developmental index (MDI)
and the psychomotor developmental index (PDI). RESULTS: Maternal intakes of n-6/n
3 PUFAs and linoleic acid (LA)-to-alpha-linolenic acid (ALA) ratio (LA/ALA) were
9.7 +/- 6.3 and 11.12 +/- 6.9, respectively. Multiple regression analysis, after
adjusting for covariates, showed that n-6/n-3 PUFAs was negatively associated
with both the MDI (beta = -0.1674, P = 0.0291) and PDI (beta = -0.1947, P =
0.0380) at 6 months of age. These inverse associations were also observed between
LA/ALA and both the MDI and PDI (MDI; beta = -0.1567; P = 0.0310, PDI; beta =
0.1855; P = 0.0367). Multiple logistic regression analysis, with the covariates,
showed that infants whose mother's LA/ALA were ranked in the 2nd, 3rd, and 4th
quartile were at approximately twice the risk with more than twice the risk of
delayed performance on the PDI compared to the lowest quartile (1st vs. 2nd; OR =
2.965; 95% CI = 1.376 - 6.390, 1st vs. 3rd; OR = 3.047; 95% CI = 1.374 - 6.756
and 1st vs. 4th; OR = 2.551; 95% CI = 1.160 - 5.607). CONCLUSIONS: Both the
maternal dietary n-6/n-3 PUFAs and LA/ALA intake were significantly associated
with the mental and psychomotor development of infants at 6 months of age. Thus,
maintaining low n-6/n-3 PUFAs and LA/ALA is encouraged for women during
pregnancy.
PMID- 28420390
TI - A novel ViewRNA in situ hybridization method for the detection of the dynamic
distribution of Classical Swine Fever Virus RNA in PK15 cells.
AB - BACKGROUND: Classical swine fever (CSF) is a highly contagious fatal infectious
disease caused by classical swine fever virus (CSFV). A better understanding of
CSFV replication is important for the study of pathogenic mechanism of CSF. With
the development of novel RNA in situ Hybridization method, quantitatively
localization and visualization of the virus RNA molecular in cultured cell or
tissue section becomes very important tool to address these pivotal pathogenic
questions. In this study, we established ViewRNA ISH method to reveal the dynamic
distribution of CSFV RNA in PK15 cells. METHODS: We designed several specific
probes of CSFV RNA and reference gene beta-actin for host PK15 cells to monitor
the relative location of CSFV RNA and house-keeping gene in the infected cells.
After determining the titer of reference strain CSFV (HeBHH1/95) with the 50%
tissue culture infective dose (TCID50), we optimized the protease K concentration
and formalin fixation time to analyze the hybridization efficiency, fluorescence
intensity and repeatability. In order to measure the sensitivity of this assay,
we compared it with the fluorescent antibody test (FAT) and
immunohistochemical(IHC) method. Specificity of the ViewRNA ISH was tested by
detecting several sub genotypes of CSFV (sub genotype 1.1, 2.1, 2.2 and 2.3)
which are present in China and other normal pig infectious virus (bovine viral
diarrhea virus (BVDV), porcine parvovirus (PPV), porcine pseudorabies virus (PRV)
and porcine circovirusII(PCV-2). RESULTS: The lowest detection threshold of the
ViewRNA ISH method was 10-8, while the sensitivity of FAT and IHC were 10-5 and
10-4, respectively. The ViewRNA ISH was specific for CSFV RNA including 1.1, 2.1,
2.2 and 2.3 subtypes, meanwhile, there was no cross-reaction with negative
control and other viruses including BVDV, PPV, PRV and PCV-2. Our results showed
that after infection at 0.5 hpi (hours post inoculation, hpi), the CSFV RNA can
be detected in nucleus and cytoplasm; during 3-9 hpi, RNA was mainly distributed
in nucleus and reached a maximum at 12hpi, then RNA copy number was gradually
increased around the cell nucleus during 24-48 hpi and reached the peak at 72hpi.
CONCLUSIONS: To our knowledge, this is the first to reveal the dynamic
distribution of medium virulence CSFV RNA in PK15 cells using the ViewRNA ISH
method. The sensitivity of the ViewRNA ISH was three to four orders of magnitude
higher than that of FAT and IHC methods. The specificity experiment showed that
the ViewRNA ISH was highly specific for CSFV and no cross-reaction occurred to
negative control and other pig infectious virus. This assay is more suitable for
studying the CSFV RNA life cycle in cell nucleus. The results proved that CSFV
RNA enters into PK15 cells earlier than 0.5hpi, relative to the eclipse period of
cytoplasm is 6-9 hpi and CSFV RNA has ever existed in nucleus.
PMID- 28420389
TI - Assessment of copy number variation in genes related to drug resistance in
Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and
a systematic review of the literature.
AB - BACKGROUND: Parasite resistance to anti-malarials represents a great obstacle for
malaria elimination. The majority of studies have investigated the association
between single-nucleotide polymorphisms (SNPs) and drug resistance; however, it
is becoming clear that the copy number variation (CNV) is also associated with
this parasite phenotype. To provide a baseline for molecular surveillance of anti
malarial drug resistance in the Brazilian Amazon, the present study characterized
the genetic profile of both markers in the most common genes associated with drug
resistance in Plasmodium falciparum and Plasmodium vivax isolates. Additionally,
these data were compared to data published elsewhere applying a systematic review
of the literature published over a 20-year time period. METHODS: The genomic DNA
of 67 patients infected by P. falciparum and P. vivax from three Brazilian States
was obtained between 2002 and 2012. CNV in P. falciparum multidrug resistance
gene-1 (pfmdr1), GTP cyclohydrolase 1 (pfgch1) and P. vivax multidrug resistance
gene-1 (pvmdr1) were assessed by real-time PCR assays. SNPs in the pfmdr1 and
pfcrt genes were assessed by PCR-RFLP. A literature search for studies that
analysed CNP in the same genes of P. falciparum and P. vivax was conducted
between May 2014 and March 2017 across four databases. RESULTS: All analysed
samples of P. falciparum carried only one copy of pfmdr1 or pfgch1. Although the
pfcrt K76T polymorphism, a determinant of CQ resistance, was present in all
samples genotyped, the pfmdr1 N86Y was absent. For P. vivax isolates, an
amplification rate of 20% was found for the pvmdr1 gene. The results of the study
are in agreement with the low amplification rates for pfmdr1 gene evidenced in
the Americas and Africa, while higher rates have been described in Southeast
Asia. For P. vivax, very low rates of amplification for pvmdr1 have been
described worldwide, with exceptions in French Guiana, Cambodia, Thailand and
Brazil. CONCLUSIONS: The present study was the first to evaluate gch1 CNV in P.
falciparum isolates from Brazil, showing an absence of amplification of this gene
more than 20 years after the withdrawal of the Brazilian antifolates therapeutic
scheme. Furthermore, the rate of pvmdr1 amplification was significantly higher
than that previously reported for isolates circulating in Northern Brazil.
PMID- 28420391
TI - Interactive, open source, travel time scenario modelling: tools to facilitate
participation in health service access analysis.
AB - BACKGROUND: Modelling travel time to services has become a common public health
tool for planning service provision but the usefulness of these analyses is
constrained by the availability of accurate input data and limitations inherent
in the assumptions and parameterisation. This is particularly an issue in the
developing world where access to basic data is limited and travel is often
complex and multi-modal. Improving the accuracy and relevance in this context
requires greater accessibility to, and flexibility in, travel time modelling
tools to facilitate the incorporation of local knowledge and the rapid
exploration of multiple travel scenarios. The aim of this work was to develop
simple open source, adaptable, interactive travel time modelling tools to allow
greater access to and participation in service access analysis. RESULTS:
Described are three interconnected applications designed to reduce some of the
barriers to the more wide-spread use of GIS analysis of service access and allow
for complex spatial and temporal variations in service availability. These
applications are an open source GIS tool-kit and two geo-simulation models. The
development of these tools was guided by health service issues from a developing
world context but they present a general approach to enabling greater access to
and flexibility in health access modelling. The tools demonstrate a method that
substantially simplifies the process for conducting travel time assessments and
demonstrate a dynamic, interactive approach in an open source GIS format. In
addition this paper provides examples from empirical experience where these tools
have informed better policy and planning. CONCLUSION: Travel and health service
access is complex and cannot be reduced to a few static modeled outputs. The
approaches described in this paper use a unique set of tools to explore this
complexity, promote discussion and build understanding with the goal of producing
better planning outcomes. The accessible, flexible, interactive and responsive
nature of the applications described has the potential to allow complex
environmental social and political considerations to be incorporated and
visualised. Through supporting evidence-based planning the innovative modelling
practices described have the potential to help local health and emergency
response planning in the developing world.
PMID- 28420392
TI - Tissue tropisms, infection kinetics, histologic lesions, and antibody response of
the MR766 strain of Zika virus in a murine model.
AB - BACKGROUND: The appearance of severe Zika virus (ZIKV) disease in the most recent
outbreak has prompted researchers to respond through the development of tools to
quickly characterize transmission and pathology. We describe here another such
tool, a mouse model of ZIKV infection and pathogenesis using the MR766 strain of
virus that adds to the growing body of knowledge regarding ZIKV kinetics in small
animal models. METHODS: We infected mice with the MR766 strain of ZIKV to
determine infection kinetics via serum viremia. We further evaluated infection
induced lesions via histopathology and visualized viral antigen via
immunohistochemical labeling. We also investigated the antibody response of
recovered animals to both the MR766 and a strain from the current outbreak
(PRVABC59). RESULTS: We demonstrate that the IRF3/7 DKO mouse is a susceptible,
mostly non-lethal model well suited for the study of infection kinetics,
pathological progression, and antibody response. Infected mice presented lesions
in tissues that have been associated with ZIKV infection in the human population,
such as the eyes, male gonads, and central nervous system. In addition, we
demonstrate that infection with the MR766 strain produces cross-neutralizing
antibodies to the PRVABC59 strain of the Asian lineage. CONCLUSIONS: This model
provides an additional tool for future studies into the transmission routes of
ZIKV, as well as for the development of antivirals and other therapeutics, and
should be included in the growing list of available tools for investigations of
ZIKV infection and pathogenesis.
PMID- 28420393
TI - Medical treatment of mammary desmoid-type fibromatosis: which benefit?
AB - BACKGROUND: Breast fibromatosis is a rare disease characterized by monoclonal
fibroblast proliferation. It has no ability to metastasize but has a high local
recurrence rate and often infiltrates surrounding tissues. Surgical treatment is
the reference, but recently, new targeted therapies have emerged. We report an
original case of a patient with breast fibromatosis who received exclusive
medical treatment. Our aim was to analyze these treatments based on the clinical
and radiological outcome, iatrogenic effects, and pharmacological action. CASE
PRESENTATION: We report the case of a 19-year-old woman who developed a desmoid
type fibromatosis of the lower inner quadrant of the right breast, measuring 50 *
25 mm (i.e., a volume of 27.4 cm3). Initial surgery was not possible because of
potential esthetic and functional prejudice. Thus, she had an exclusive medical
treatment including several lines: NSAIDs with tamoxifen and triptorelin,
followed by sorafenib, then interferon alpha2b, and finally sunitinib. With
tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was
observed (57% reduction of the maximal tumoral volume). For each treatment, we
provided the clinical and radiological outcome in association with known
pharmacological action. CONCLUSIONS: TKI had been an interesting alternative
option to initial surgery, providing at least a partial response and potentially
allowing less mutilating surgery. However, no pharmacological mechanism can
unequivocally explain TKI efficacy. In general, breast fibromatosis should be
treated along with oncologist and interventional radiologists in a trans
disciplinary modality, thus offering an adapted treatment for this particular
desmoid-type fibromatosis localization.
PMID- 28420394
TI - Influence maternal background has on children's mental health.
AB - BACKGROUND: In this paper, we aim to discern how a mother's health and her
socioeconomic determinants may influence her children's mental health. In
addition to this, we also evaluate the influence of other household
characteristics and whether or not the economic downturn has heightened the
effect a parent's social gradient has on their children's mental health. METHODS:
We use samples comprised of 4-14-year-old minors from the 2006 Spanish National
Health Survey (SNHS), undertaken prior to the crisis, and the 2011 SNHS, carried
out during the crisis. The participating children's mental health is assessed
using the Strengths and Difficulties Questionnaire (SDQ). Mixed models are used
to evaluate the influence a mother's health and her socioeconomic status may have
on her children's mental health. We also add interactions to observe the effect
specific socioeconomic determinants may have had during the economic downturn.
RESULTS: The risk of a child suffering from mental health disorders increases
when their mother has mental health problems. Socioeconomic determinants also
play a role, as a low socioeconomic status (SES) increases the risk of a child
exhibiting behavioural problems, being hyperactive or antisocial, whereas when a
mother has attained a high level of education, this significantly reduces the
probability of a child having mental health problems. 'Homemaker' is the activity
status most positively related to children's mental health. The findings show
that the Spanish economic downturn has not significantly changed children's
mental health problems and the negative effects of low maternal SES are no
greater than they were before the crisis. The main difference in 2011, with
respect to 2006, is that the risk of children suffering from mental health
problems is higher when their parents are (long or short-term) unemployed.
CONCLUSIONS: In conclusion, both a mother's health and her socioeconomic status,
as well as other household characteristics, are found to be related to her
children's mental well-being. Although the crisis has not significantly changed
mental health disorders in children or the social gradient of parents in general,
at-risk children are the most negatively affected in the Spanish economic
downturn.
PMID- 28420395
TI - Characteristics of first-time varenicline users - A cross-sectional study in
Finnish quitters.
AB - BACKGROUND: Varenicline is an efficacious medicine for smoking cessation (SC) but
little is known about the characteristics of varenicline users. This study
examined the characteristics of first-time (naive) varenicline users in Finland
and compared those who had previously used SC pharmacotherapy to those who were
trying SC pharmacotherapy for the first time. METHODS: A cross-sectional survey
was conducted in Finnish community pharmacies between February 2014 and January
2015. Pharmacy customers purchasing a varenicline starter package for the first
time ever were asked to complete a questionnaire or to participate in a
structured interview conducted by the pharmacist (identical questions). The
questionnaire included questions about demographic characteristics, smoking
habits, previous cessation attempts and factors associated with varenicline use.
RESULTS: Altogether 98 people completed the survey. The majority were daily
smokers (96%, n = 94), with a history of over 10 years of regular smoking (94%, n
= 92), and a strong/very strong nicotine dependence (67%, n = 66). Half of the
participants (54%, n = 53) were trying a SC pharmacotherapy for the first time.
Demographic characteristics and smoking habits were similar between first-time
and previous users of SC medications (p > 0.05). Health centers (42%, n = 41) and
occupational health care clinics (37%, n = 36) were the most common sources of
varenicline prescriptions. The majority of participants received the prescription
for varenicline after mentioning their desire for quitting to a physician (70%, n
= 69). CONCLUSIONS: Considering the relatively large proportion of SC naive
medicine users among new users of varenicline, smokers who have previously been
reluctant to quit smoking, to use other pharmacological SC interventions, or
perhaps unaware of these options may be interested in attempting cessation with
varenicline. Most participants made the initiative to discuss their smoking with
the physician, which led to varenicline prescribing. This suggests that
physicians may not satisfactorily recognize their patients' nicotine dependence
and desire to quit, and they should more actively support patients' smoking
cessation.
PMID- 28420396
TI - Determinants of village doctors' job satisfaction under China's health sector
reform: a cross-sectional mixed methods study.
AB - BACKGROUND: To strengthen rural health workforce, the Chinese government has
launched a series of policies to promote the job satisfaction of village doctors
since the health sector reform. The purpose of this mixed-method study is to
describe village doctors' job satisfaction under the context of health sector
reform and investigate the associated factors. METHODS: Data was obtained from a
survey of village doctors across three Chinese provinces in 2014. Using a
multistage sampling process, quantitative data was collected from village doctors
through the self-administered questionnaire and analyzed by multilevel logistic
regression models. Qualitative data was collected through face-to-face semi
structured interviews on both village doctors and health managers. Theoretical
coding was then conducted to analyze qualitative data. RESULTS: Among the 1221
respondents, 48.6% felt satisfied with their job. Older village doctors with less
of a workload and under high-level integrated management were more likely to feel
satisfied with their job. Village doctors who earned the top level of monthly
income felt more satisfied, while on the county level, those who lived in
counties with the highest GDP felt less satisfied. However, enrollment in a
pension plan showed no significant difference in regards to village doctors' job
satisfaction. Among 34 participants of qualitative interviews, most believed that
age, income, and integrated management had a positive influence on the job
satisfaction, while pension plan and basic public health care policies exhibited
negative effects. Also, the increasing in availability of healthcare and health
resources along with local economic development had negative effects on village
doctors' job satisfaction. CONCLUSION: Village doctors' job satisfaction was
quite low in regards to several determinants including age, income, workload,
enrollment in a pension plan, integrated management, and county economic and
medical availability development.
PMID- 28420397
TI - Responsiveness of the short-form health survey and the Parkinson's disease
questionnaire in patients with Parkinson's disease.
AB - BACKGROUND: The responsiveness of a measurement instrument is important for
understanding its ability to detect changes in the progression of a disease. We
examined and compared the internal and external responsiveness of the 36-item
Short-Form Health Survey (SF-36) and the 39-item Parkinson's Disease
Questionnaire (PDQ-39) in patients with Parkinson's Disease (PD). METHODS:
Seventy-four patients with PD were evaluated using the SF-36 and PDQ-39 at
baseline and again after one year. In addition, their motor signs, motor
difficulties of daily living, and depressive symptoms were assessed as external
criteria. The internal responsiveness was examined using effect size,
standardized response mean, and the Wilcoxon signed rank test. The external
responsiveness was examined using receiver operating characteristic curves,
correlation analyses, and regression models. RESULTS: Both instruments were
partially sensitive to changes during the 1-year follow-up and able to
discriminate between patients with improved versus deteriorated motor signs. In
addition, both were similarly responsive to changes in the motor difficulties of
daily living; the SF-36 appeared to be more sensitive than the PDQ-39 to changes
in depressive symptoms. CONCLUSIONS: The SF-36 and the PDQ-39 were acceptably
internally and externally responsive during the 1-year follow-up.
PMID- 28420398
TI - Mechanisms of corticosteroid insensitivity in COPD alveolar macrophages exposed
to NTHi.
AB - BACKGROUND: Non-typeable Haemophilus influenza (NTHi) infection is common in
COPD. Corticosteroids can have limited therapeutic effects in COPD patients. NTHi
causes corticosteroid insensitive cytokine production from COPD alveolar
macrophages. We investigated the mechanisms by which NTHi causes corticosteroid
insensitive inflammatory responses, and the effects of NTHi exposure on COPD
macrophage polarisation. METHOD: Alveolar macrophages from COPD patients and
controls were exposed to NTHi in conjunction with the corticosteroid
dexamethasone and/or the p38 MAPK inhibitor BIRB-796. Cytokine release, GR
phosphorylation and modulation and macrophage phenotype were analysed. RESULTS:
Dexamethasone significantly inhibited NTHi induced TNF-alpha, IL-6 and IL-10 from
COPD macrophages but, CXCL8 was not suppressed. BIRB-796 combined with
dexamethasone caused significantly greater inhibition of all cytokines than
either drug alone (p < 0.05 all comparisons). NTHi caused phosphorylation of GR
S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK. NTHi
altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206,
CD163 and HLA-DR. CONCLUSION: NTHi exposure causes p38 MAPK dependent GR
phosphorylation associated with decreased GR function in COPD alveolar
macrophages. Combining a p38 MAPK inhibitor with corticosteroids can enhance anti
inflammatory effects during NTHi exposure of COPD alveolar macrophages. NTHi
causes macrophage polarisation that favours bacterial persistence.
PMID- 28420399
TI - Distinct parasite populations infect individuals identified through passive and
active case detection in a region of declining malaria transmission in southern
Zambia.
AB - BACKGROUND: Substantial reductions in the burden of malaria have been documented
in parts of sub-Saharan Africa, with elimination strategies and goals being
formulated in some regions. Within this context, understanding the epidemiology
of low-level malaria transmission is crucial to achieving and sustaining
elimination. A 24 single-nucleotide-polymorphism Plasmodium falciparum molecular
barcode was used to characterize parasite populations from infected individuals
identified through passive and active case detection in an area approaching
malaria elimination in southern Zambia. METHODS: The study was conducted in the
catchment area of Macha Hospital in Choma District, Southern Province, Zambia,
where the parasite prevalence declined over the past decade, from 9.2% in 2008 to
less than 1% in 2013. Parasite haplotypes from actively detected, P. falciparum
infected participants enrolled in a serial cross-sectional, community-based
cohort study from 2008 to 2013 and from passively detected, P. falciparum
infected individuals enrolled at five rural health centres from 2012 to 2015 were
compared. Changes in P. falciparum genetic relatedness, diversity and complexity
were analysed as malaria transmission declined. RESULTS: Actively detected cases
identified in the community were most commonly rapid diagnostic test negative,
asymptomatic and had submicroscopic parasitaemia. Phylogenetic reconstruction
using concatenated 24 SNP barcode revealed a separation of parasite haplotypes
from passively and actively detected infections, consistent with two genetically
distinct parasite populations. For passively detected infections identified at
health centres, the proportion of detectable polyclonal infections was
consistently low in all seasons, in contrast with actively detected infections in
which the proportion of polyclonal infections was high. The mean genetic
divergence for passively detected infections was 34.5% for the 2012-2013
transmission season, 37.8% for the 2013-2014 season, and 30.8% for the 2014-2015
season. The mean genetic divergence for actively detected infections was 22.3% in
the 2008 season and 29.0% in the 2008-2009 season and 9.9% across the 2012-2014
seasons. CONCLUSIONS: Distinct parasite populations were identified among
infected individuals identified through active and passive surveillance,
suggesting that infected individuals detected through active surveillance may not
have contributed substantially to ongoing transmission. As parasite prevalence
and diversity within these individuals declined, resource-intensive efforts to
identify the chronically infected reservoir may not be necessary to eliminate
malaria in this setting.
PMID- 28420400
TI - Erratum to: New developments in anti-malarial target candidate and product
profiles.
PMID- 28420401
TI - Using media to impact health policy-making: an integrative systematic review.
AB - INTRODUCTION: Media interventions can potentially play a major role in
influencing health policies. This integrative systematic review aimed to assess
the effects of planned media interventions-including social media-on the health
policy-making process. METHODS: Eligible study designs included randomized and
non-randomized designs, economic studies, process evaluation studies, stakeholder
analyses, qualitative methods, and case studies. We electronically searched
Medline, EMBASE, Communication and Mass Media Complete, Cochrane Central Register
of Controlled Trials, and the WHO Global Health Library. We followed standard
systematic review methodology for study selection, data abstraction, and risk of
bias assessment. RESULTS: Twenty-one studies met our eligibility criteria: 10
evaluation studies using either quantitative (n = 7) or qualitative (n = 3)
designs and 11 case studies. None of the evaluation studies were on social media.
The findings of the evaluation studies suggest that media interventions may have
a positive impact when used as accountability tools leading to prioritizing and
initiating policy discussions, as tools to increase policymakers' awareness, as
tools to influence policy formulation, as awareness tools leading to policy
adoption, and as awareness tools to improve compliance with laws and regulations.
In one study, media-generated attention had a negative effect on policy advocacy
as it mobilized opponents who defeated the passage of the bills that the media
intervention advocated for. We judged the confidence in the available evidence as
limited due to the risk of bias in the included studies and the indirectness of
the evidence. CONCLUSION: There is currently a lack of reliable evidence to guide
decisions on the use of media interventions to influence health policy-making.
Additional and better-designed, conducted, and reported primary research is
needed to better understand the effects of media interventions, particularly
social media, on health policy-making processes, and the circumstances under
which media interventions are successful. TRIAL REGISTRATION: PROSPERO 2015:
CRD42015020243.
PMID- 28420402
TI - SSER: Species specific essential reactions database.
AB - BACKGROUND: Essential reactions are vital components of cellular networks. They
are the foundations of synthetic biology and are potential candidate targets for
antimetabolic drug design. Especially if a single reaction is catalyzed by
multiple enzymes, then inhibiting the reaction would be a better option than
targeting the enzymes or the corresponding enzyme-encoding gene. The existing
databases such as BRENDA, BiGG, KEGG, Bio-models, Biosilico, and many others
offer useful and comprehensive information on biochemical reactions. But none of
these databases especially focus on essential reactions. Therefore, building a
centralized repository for this class of reactions would be of great value.
DESCRIPTION: Here, we present a species-specific essential reactions database
(SSER). The current version comprises essential biochemical and transport
reactions of twenty-six organisms which are identified via flux balance analysis
(FBA) combined with manual curation on experimentally validated metabolic network
models. Quantitative data on the number of essential reactions, number of the
essential reactions associated with their respective enzyme-encoding genes and
shared essential reactions across organisms are the main contents of the
database. CONCLUSION: SSER would be a prime source to obtain essential reactions
data and related gene and metabolite information and it can significantly
facilitate the metabolic network models reconstruction and analysis, and drug
target discovery studies. Users can browse, search, compare and download the
essential reactions of organisms of their interest through the website
http://cefg.uestc.edu.cn/sser .
PMID- 28420403
TI - Molecular surveillance of Plasmodium falciparum drug resistance in the Republic
of Congo: four and nine years after the introduction of artemisinin-based
combination therapy.
AB - BACKGROUND: Resistance to anti-malarial drugs hinders efforts on malaria
elimination and eradication. Following the global spread of chloroquine-resistant
parasites, the Republic of Congo adopted artemisinin-based combination therapy
(ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the
impacts after implementation of ACT, a molecular surveillance for anti-malarial
drug resistance was conducted in Congo 4 and 9 years after the introduction of
ACT. METHODS: Blood samples of 431 febrile children aged 1-10 years were utilized
from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All
samples were screened for malaria parasites using nested PCR. Direct sequencing
was used to determine the frequency distribution of genetic variants in the anti
malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6,
Pfk13) in malaria-positive isolates. RESULTS: One-hundred and nineteen (N = 70
from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A
relative decrease in the proportion of chloroquine-resistant haplotype (CVIET)
from 100% in 2005, 1 year before the introduction and implementation of ACT in
2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug
transporter gene, a considerable reduction in the frequency of the mutations N86Y
(from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence
of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015).
Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced
to null in 2015. None of the parasites harboured the Pfk13 mutations associated
with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new
Pfk13 variants are reported among the investigated isolates. CONCLUSION: The
implementation of ACT has led to the decline in prevalence of chloroquine
resistant parasites in the Republic of Congo. However, the constant prevalence of
the PfMDR1 Y184F mutation, associated with lumefantrine susceptibility, indicate
a selective drug pressure still exists. Taken together, this study could serve as
the basis for epidemiological studies monitoring the distribution of molecular
markers of artemisinin resistance in the Republic of Congo.
PMID- 28420404
TI - Development of a spatial sampling protocol using GIS to measure health
disparities in Bobo-Dioulasso, Burkina Faso, a medium-sized African city.
AB - BACKGROUND: Many cities in developing countries experience an unplanned and rapid
growth. Several studies have shown that the irregular urbanization and equipment
of cities produce different health risks and uneven exposure to specific
diseases. Consequently, health surveys within cities should be carried out at the
micro-local scale and sampling methods should try to capture this urban
diversity. METHODS: This article describes the methodology used to develop a
multi-stage sampling protocol to select a population for a demographic survey
that investigates health disparities in the medium-sized city of Bobo-Dioulasso,
Burkina Faso. It is based on the characterization of Bobo-Dioulasso city typology
by taking into account the city heterogeneity, as determined by analysis of the
built environment and of the distribution of urban infrastructures, such as
healthcare structures or even water fountains, by photo-interpretation of aerial
photographs and satellite images. Principal component analysis and hierarchical
ascendant classification were then used to generate the city typology. RESULTS:
Five groups of spaces with specific profiles were identified according to a set
of variables which could be considered as proxy indicators of health status.
Within these five groups, four sub-spaces were randomly selected for the study.
We were then able to survey 1045 households in all the selected sub-spaces. The
pertinence of this approach is discussed regarding to classical sampling as
random walk method for example. CONCLUSION: This urban space typology allowed to
select a population living in areas representative of the uneven urbanization
process, and to characterize its health status in regards to several indicators
(nutritional status, communicable and non-communicable diseases, and anaemia).
Although this method should be validated and compared with more established
methods, it appears as an alternative in developing countries where geographic
and population data are scarce.
PMID- 28420405
TI - Do International Health Partnerships contribute to reverse innovation? a mixed
methods study of THET-supported partnerships in the UK.
AB - BACKGROUND: International health partnerships (IHPs) are changing, with an
increased emphasis on mutual accountability and joint agenda setting for both the
high- and the low- or middle-income country (LMIC) partners. There is now an
important focus on the bi-directionality of learning however for the UK partners,
this typically focuses on learning at the individual level, through personal and
professional development. We sought to evaluate whether this learning also takes
the shape of 'Reverse Innovation' -when an idea conceived in a low-income country
is subsequently adopted in a higher-income country. METHODS: This mixed methods
study used an initial scoping survey of all the UK-leads of the Tropical Health
Education Trust (THET)-supported International Health Partnerships (n = 114) to
ascertain the extent to which the IHPs are or have been vehicles for Reverse
Innovation. The survey formed the sampling frame for further deep-dive interviews
to focus on volunteers' experiences and attitudes to learning from LMICs.
Interviews of IHP leads (n = 12) were audio-recorded and transcribed verbatim.
Survey data was analysed descriptively. Interview transcripts were coded
thematically, using an inductive approach. RESULTS: Survey response rate was 27%
(n = 34). The majority (70%) strongly agreed that supporting LMIC partners best
described the mission of the partnership but only 13% of respondents strongly
agreed that learning about new innovations and models was a primary mission of
their partnership. Although more than half of respondents reported having
observed innovative practice in the LMIC, only one IHP respondent indicated that
this has led to Reverse Innovation. Interviews with a sample of survey
respondents revealed themes primarily around how learning is conceptualised, but
also a central power imbalance between the UK and LMIC partners. Paternalistic
notions of knowledge could be traced to partnership power dynamics and latent
attitudes to LMICs. CONCLUSIONS: Given the global flow of innovation, if High
income countries (HICs) are to benefit from LMIC practices, it is paramount to
keep an open mind about where such learning can come from. Making the potential
for learning more explicit and facilitating innovation dissemination upon return
will ultimately underpin the success of adoption.
PMID- 28420406
TI - Genomics insights into different cellobiose hydrolysis activities in two
Trichoderma hamatum strains.
AB - BACKGROUND: Efficient biomass bioconversion is a promising solution to
alternative energy resources and environmental issues associated with
lignocellulosic wastes. The Trichoderma species of cellulolytic fungi have strong
cellulose-degrading capability, and their cellulase systems have been extensively
studied. Currently, a major limitation of Trichoderma strains is their low
production of beta-glucosidases. RESULTS: We isolated two Trichoderma hamatum
strains YYH13 and YYH16 with drastically different cellulose degrading
efficiencies. YYH13 has higher cellobiose-hydrolyzing efficiency. To understand
mechanisms underlying such differences, we sequenced the genomes of YYH13 and
YYH16, which are essentially identical (38.93 and 38.92 Mb, respectively) and are
similar to that of the T. hamatum strain GD12. Using GeneMark-ES, we annotated
11,316 and 11,755 protein-coding genes in YYH13 and YYH16, respectively.
Comparative analysis identified 13 functionally important genes in YYH13 under
positive selection. Through examining orthologous relationships, we identified
172,655, and 320 genome-specific genes in YYH13, YYH16, and GD12, respectively.
We found 15 protease families that show differences between YYH13 and YYH16.
Enzymatic tests showed that exoglucanase, endoglucanase, and beta-glucosidase
activities were higher in YYH13 than YYH16. Additionally, YYH13 contains 10
families of carbohydrate-active enzymes, including GH1, GH3, GH18, GH35, and GH55
families of chitinases, glucosidases, galactosidases, and glucanases, which are
subject to stronger positive selection pressure. Furthermore, we found that the
beta-glucosidase gene (YYH1311079) and pGEX-KG/YYH1311079 bacterial expression
vector may provide valuable insight for designing beta-glucosidase with higher
cellobiose-hydrolyzing efficiencies. CONCLUSIONS: This study suggests that the
YYH13 strain of T. hamatum has the potential to serve as a model organism for
producing cellulase because of its strong ability to efficiently degrade
cellulosic biomass. The genome sequences of YYH13 and YYH16 represents a valuable
resource for studying efficient production of biofuels.
PMID- 28420407
TI - Understanding Phlebotomus perniciosus abundance in south-east Spain: assessing
the role of environmental and anthropic factors.
AB - BACKGROUND: Leishmaniosis is associated with Phlebotomus sand fly vector density,
but our knowledge of the environmental framework that regulates highly
overdispersed vector abundance distributions is limited. We used a standardized
sampling procedure in the bioclimatically diverse Murcia Region in Spain and
multilevel regression models for count data to estimate P. perniciosus abundance
in relation to environmental and anthropic factors. METHODS: Twenty-five dog and
sheep premises were sampled for sand flies using adhesive and light-attraction
traps, from late May to early October 2015. Temperature, relative humidity and
other animal- and premise-related data recorded on site and other environmental
data were extracted from digital databases using a geographical information
system. The relationship between sand fly abundance and explanatory variables was
analysed using binomial regression models. RESULTS: The total number of sand
flies captured, mostly with light-attraction traps, was 3,644 specimens,
including 80% P. perniciosus, the main L. infantum vector in Spain. Abundance
varied between and within zones and was positively associated with increasing
altitude from 0 to 900 m above sea level, except from 500 to 700 m where it was
low. Populations peaked in July and especially during a 3-day heat wave when
relative humidity and wind speed plummeted. Regression models indicated that
climate and not land use or soil characteristics have the greatest impact on this
species density on a large geographical scale. In contrast, micro-environmental
factors such as animal building characteristics and husbandry practices affect
sand fly population size on a smaller scale. CONCLUSIONS: A standardised sampling
procedure and statistical analysis for highly overdispersed distributions allow
reliable estimation of P. perniciosus abundance and identification of
environmental drivers. While climatic variables have the greatest impact at macro
environmental scale, anthropic factors may be determinant at a micro-geographical
scale. These finding may be used to elaborate predictive distribution maps useful
for vector and pathogen control programs.
PMID- 28420408
TI - Sialylation regulates myofibroblast differentiation of human skin fibroblasts.
AB - BACKGROUND: Fibroblasts are key players in maintaining skin homeostasis and in
orchestrating physiological tissue repair and skin regeneration. Dysfunctions in
fibroblasts that occur with aging and the senescent process lead to the delayed
healing observed in elderly people. The molecular mechanisms leading to
fibroblast dysfunction during aging and the senescent process have not yet been
clarified. Previously, changes in patterns of glycosylation were observed in
fibroblasts in aging and the senescent process, but the effect of these changes
on the function of fibroblasts has not been well documented. Here, we
investigated whether changes in glycosylation during the process to senescence
may have functional effects on fibroblasts. METHODS: The changes in cell surface
glycans on skin fibroblasts during the process to senescence were examined in
early-passage (EP) and late-passage (LP) skin fibroblasts by fluorescence
activated cell sorting analysis using lectins. The contributors to the changes in
cell surface glycans were examined by real-time polymerase chain reaction or
Western blot analysis. The effects of changes in glycosylation on proliferation,
migration, induction of cellular senescence, and myofibroblast differentiation
induced by transforming growth factor (TGF)-beta1 stimulation were examined in EP
fibroblasts. The changes in glycosylation were performed by GalNAc-alpha-O-benzyl
or sialidase treatment. RESULTS: A decrease in sialylation of glycoproteins and
an increase in sialidase NEU1 were observed in LP fibroblasts. The reduction of
sialylation did not have any effect on proliferation, migration, or induction of
cellular senescence. On the other hand, myofibroblast differentiation was
inhibited by the reduction of sialylation, indicating that sialylation is
important for myofibroblast differentiation. The localization of CD44 in lipid
rafts, which is required for myofibroblast differentiation, was inhibited by the
reduction of sialylation. Furthermore, reduced myofibroblast differentiation in
LP fibroblasts was restored by a sialidase inhibitor. CONCLUSIONS: Desialylation
of CD44 with increased sialidase during the process to senescence reduced the
localization of CD44 in lipid rafts after TGF-beta1 stimulation, leading to the
inhibition of myofibroblast differentiation. Thus, regulation of sialylation may
be an attractive strategy for the prevention and regenerative therapy of age
related skin diseases, cosmetic skin alterations, and chronic wounds caused by
delayed healing in elderly people.
PMID- 28420409
TI - Assessing the status of iodine deficiency disorder (IDD) and associated factors
in Wolaita and Dawro Zones School Adolescents, southern Ethiopia.
AB - BACKGROUND: Iodine deficiency is the major preventable cause of irreversible
mental retardation in the world. Ethiopia is a country with high prevalence of
iodine deficiency disorders which continue to affect a large number of the
country's population. The aim of the study was to assess the prevalence of iodine
deficiency disorder in Wolaita and Dawuro zones. METHODS: A descriptive, cross
sectional study was conducted in high school and preparatory students in Wolaita
and Dawuro zones between April and May 2012. Data were collected from 718 school
adolescents using pre-tested questionnaire through systematic random sampling
technique. Data were entered and cleaned using Epi-info version 3.5.3 and then
transported to SPSS version 20 for analysis. Bivariate and Multivariable logistic
regression were done and the cut off value set was P < 0.05 as this is considered
as statistically significant. RESULT: The overall prevalence (total goiter rate)
of goiter in study area was 351 (48.9%). Students with Grade-1 goiter were 265
(36.9%) while with Grade-2 goiter was 86 (11.9%). Females were by a long way
vulnerable for goiter and accounts 60.9% with Pearson correlation coefficient
0.300, P value 0.0001. Generally, the occurrence of goiter in the study area was
found to have statistical significant association with sex of respondents (being
female) [AOR = 3.526; 95% CI (2.55-4.87)], climatic condition of resident
(temperate climate) [AOR = 0.617; 95% CI (0.404-0.943)], frequency of iodized
salt use [AOR = 0.484; 95% CI (0.317-0.739)] and consumption of cassava [AOR =
4.184; 95% CI (2.6-6.707)]. CONCLUSION AND RECOMMENDATION: In general, the study
revealed that iodine deficiency disorder was a serious public health concern.
Nearly half of adolescent students in Wolaita and Dawuro zones were affected by
goiter. Therefore, emphasis on a sustainable iodine intervention program targeted
at population level, particularly at females is mandatory. Nutrition education
along with adequate Universal Salt Iodization program is urgently required.
PMID- 28420410
TI - Ethnopharmacologic survey of medicinal plants used to treat human diseases by
traditional medical practitioners in Dega Damot district, Amhara, Northwestern
Ethiopia.
AB - BACKGROUND: One of the services that plants provide for human beings is their
wider medicinal application. Although it is not fully assessed, the practice and
wider use of traditional medicine is frequent in Ethiopia. Studies conducted
previously are confined to the perceptions of modern and traditional health
practitioners about traditional medicine. A total of 45 informants were selected
purposefully from the study area. For collecting the data, semi-structured
interviewees, observation and field walks were employed from August 10 to
September 30/2014. To summarize the information, descriptive statistical methods
were applied. RESULTS: Sixty species of medicinal plants distributed in 42
families were collected and identified applied locally for the treatment of 55
human disorders. The most commonly treated ones were evil eye, malaria, wound,
peptic ulcer disease and rabies. According to this study, leaves were the
commonly used plant parts (36.5%) and 39% of the preparations were decoctions.
Oral route, 43 (44%) was the commonly used route of application whereas most
(54.8%) remedies were administered only once. Fourteen percent of preparations
caused vomiting in addition most (40.4%) of the formulations was contraindicated
for pregnant patients. Only seventeen percent of the formulations possessed drug
food interactions. Most preparations were stored within clothes, 31 (29.8%).
There exists a high (ICF = 0.8) evenness of plant use among healers for treating
respiratory problems. Alliumsativum (FI = 0.75) for evil eye, Phytolacca
dodecandra (FI = 0.8) for rabies and Croton macrostachyus (FI = 0.78) for
treating malaria were medicinal plants with highest fidelity levels showing
consistency of knowledge on species best treating power. This study also
documented that drought, overgrazing and firewood collection are major threats.
CONCLUSION: Dega Damot district is loaded in its medicinal plant diversity and
indigenous knowledge though plants are highly affected by drought, overgrazing
and firewood collection. Therefore awareness activities must be created among the
district's population by concerned governmental and nongovernmental organizations
about the value of medicinal plants and conservation of these plants. The healing
potential and associated adverse issues of the claimed medicinal plants should be
assessed before proposing for a broader utilization.
PMID- 28420411
TI - Characterization of a novel aspartyl protease inhibitor from Haemonchus
contortus.
AB - BACKGROUND: Aspartyl protease inhibitor (API) was thought to protect intestinal
parasitic nematodes from their hostile proteolytic environment. Studies on
Ostertagia ostertagi, Ascaris suum and Brugia malayi indicated that aspins might
play roles in nematode infection. In a recent study, proteins differentially
expressed between free-living third-stage larvae (L3) and activated L3 (xL3) of
Haemonchus contortus were identified by 2D-DIGE. API was found downregulated in
xL3 when compared with L3. However, there was no report about the functions of H.
contortus API in the parasite-host interaction. In this study, the gene encoding
API from H. contortus was cloned, expressed, and part of its biological
characteristics were studied. RESULTS: A DNA fragment of 681 bp was amplified by
RT-PCR. Ninety one percent of the amino acid sequence was similar with that for
aspin from O. ostertagi. The recombinant API protein was fusion-expressed with a
molecular weight of 48 * 103. Results of Western blot showed that the recombinant
API could be recognized by serum from goat infected with H. contortus. It was
found that API was localized exclusively in the subcutaneous tissue and
epithelial cells of the gastrointestinal tract in adult H. contortus. qRT-PCR
suggested that the API gene was differentially transcribed in different life
cycle stages, with the lowest level in female adults and the highest in free
living L3 larvae. Enzyme inhibition assay indicated that the recombinant API can
inhibit the activity of pepsin significantly, and the optimal reaction pH and
temperature were 4.0 and 37-50 degrees C respectively. In vitro study showed
that the recombinant API could induce goat PBMCs to express IFN-gamma, IL-4 and
IL-10. CONCLUSIONS: A new aspartyl protease inhibitor was cloned from H.
contortus and its characteristics were studied for the first time. The results
indicate that API may regulate the immune response of the host and play roles in
the infection.
PMID- 28420412
TI - Intersect-then-combine approach: improving the performance of somatic variant
calling in whole exome sequencing data using multiple aligners and callers.
AB - Bioinformatic analysis of genomic sequencing data to identify somatic mutations
in cancer samples is far from achieving the required robustness and
standardisation. In this study we generated a whole exome sequencing benchmark
dataset using the platinum genome sample NA12878 and developed an intersect-then
combine (ITC) approach to increase the accuracy in calling single nucleotide
variants (SNVs) and indels in tumour-normal pairs. We evaluated the effect of
alignment, base quality recalibration, mutation caller and filtering on
sensitivity and false positive rate. The ITC approach increased the sensitivity
up to 17.1%, without increasing the false positive rate per megabase (FPR/Mb) and
its validity was confirmed in a set of clinical samples.
PMID- 28420413
TI - Is combined use of intravenous and intraarticular tranexamic acid superior to
intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A
meta-analysis of randomized controlled trials.
AB - BACKGROUND: Tranexamic acid (TXA) has been proven to be effective in reducing
blood loss and transfusion rate after total knee arthroplasty (TKA) without
increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).
Recently, an increasing number of studies have been interested in applying
combined intravenous (IV) with intraarticular (IA) tranexamic acid in total knee
arthroplasty. The purpose of this meta-analysis was to compare the blood loss and
complications of combined TXA with IV TXA or IA TXA on TKA. METHODS: Systematic
search of literatures were conducted to identify related articles that were
published in PubMed, MEDLINE, Embase, the Cochrane Library, SpringerLink,
ClinicalTrials.gov, and Ovid from their inception to September 2016. All studies
that compare blood loss and complications of combined TXA and IV TXA or IA TXA on
TKA were included. Main outcomes were collected and analyzed by the Review
Manager 5.3. RESULTS: Five studies were included in the present meta-analysis.
There was significant difference in total blood loss and blood volume of drainage
when compared combined TXA group with IV TXA group or IA TXA group (P < 0.05).
There was no difference in transfusion rate and thromboembolic complications when
comparing combined TXA with IV TXA or IA TXA alone (P > 0.05). CONCLUSIONS:
Compared with administration of IA TXA or IV TXA alone on TKA, combined use of
TXA has advantages in reducing total blood loss and blood volume of drainage
without increasing the incidence of thromboembolic complications. We recommend
combined TXA as the preferred option for patients undergoing TKA.
PMID- 28420414
TI - Integrated genomic analysis of mitochondrial RNA processing in human cancers.
AB - BACKGROUND: The mitochondrial genome is transcribed as continuous polycistrons of
RNA containing multiple genes. As a consequence, post-transcriptional events are
critical for the regulation of gene expression and therefore all aspects of
mitochondrial function. One particularly important process is the m1A/m1G RNA
methylation of the ninth position of different mitochondrial tRNAs, which allows
efficient processing of mitochondrial mRNAs and protein translation, and de
regulation of genes involved in these processes has been associated with altered
mitochondrial function. Although mitochondria play a key role in cancer, the
status of mitochondrial RNA processing in tumorigenesis is unknown. METHODS: We
measure and assess mitochondrial RNA processing using integrated genomic analysis
of RNA sequencing and genotyping data from 1226 samples across 12 different
cancer types. We focus on the levels of m1A and m1G RNA methylation in
mitochondrial tRNAs in normal and tumor samples and use supervised and
unsupervised statistical analysis to compare the levels of these modifications to
patient whole genome genotypes, nuclear gene expression, and survival outcomes.
RESULTS: We find significant changes to m1A and m1G RNA methylation levels in
mitochondrial tRNAs in tumor tissues across all cancers. Pathways of RNA
processing are strongly associated with methylation levels in normal tissues (P =
3.27 * 10-31), yet these associations are lost in tumors. Furthermore, we report
18 gene-by-disease-state interactions where altered RNA methylation levels occur
under cancer status conditional on genotype, implicating genes associated with
mitochondrial function or cancer (e.g., CACNA2D2, LMO2, and FLT3) and suggesting
that nuclear genetic variation can potentially modulate an individual's ability
to maintain unaltered rates of mitochondrial RNA processing under cancer status.
Finally, we report a significant association between the magnitude of methylation
level changes in tumors and patient survival outcomes. CONCLUSIONS: We report
widespread variation of mitochondrial RNA processing between normal and tumor
tissues across all cancer types investigated and show that these alterations are
likely modulated by patient genotype and may impact patient survival outcomes.
These results highlight the potential clinical relevance of altered mitochondrial
RNA processing and provide broad new insights into the importance and complexity
of these events in cancer.
PMID- 28420415
TI - Distribution pattern following systemic mesenchymal stem cell injection depends
on the age of the recipient and neuronal health.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) show therapeutic efficacy in many
different age-related degenerative diseases, including Alzheimer's disease. Very
little is currently known about whether or not aging impacts the transplantation
efficiency of MSCs. METHODS: In this study, we investigated the distribution of
intravenously transplanted syngeneic MSCs derived from young and aged mice into
young, aged, and transgenic APP/PS1 Alzheimer's disease mice. MSCs from male
donors were transplanted into female mice and their distribution pattern was
monitored by PCR using Y-chromosome specific probes. Biodistribution of
transplanted MSCs in the brains of APP/PS1 mice was additionally confirmed by
immunofluorescence and confocal microscopy. RESULTS: Four weeks after
transplantation into young mice, young MSCs were found in the lung, axillary
lymph nodes, blood, kidney, bone marrow, spleen, liver, heart, and brain cortex.
In contrast, young MSCs that were transplanted into aged mice were only found in
the brain cortex. In both young and aged mouse recipients, transplantation of
aged MSCs showed biodistribution only in the blood and spleen. Although young
transplanted MSCs only showed neuronal distribution in the brain cortex in young
mice, they exhibited a wide neuronal distribution pattern in the brains of
APP/PS1 mice and were found in the cortex, cerebellum, hippocampus, olfactory
bulb, and brainstem. The immunofluorescent signal of both transplanted MSCs and
resident microglia was robust in the brains of APP/PS1 mice. Monocyte
chemoattractant-1 levels were lowest in the brain cortex of young mice and were
significantly increased in APP/PS1 mice. Within the hippocampus, monocyte
chemoattractant-1 levels were significantly higher in aged mice compared with
younger and APP/PS1 mice. CONCLUSIONS: We demonstrate in vivo that MSC
biodistribution post transplantation is detrimentally affected by aging and
neuronal health. Aging of both the recipient and the donor MSCs used attenuates
transplantation efficiency. Clinically, our data would suggest that aged MSCs
should not be used for transplantation and that transplantation of MSCs into aged
patients will be less efficacious.
PMID- 28420416
TI - Emerging therapies for acute myeloid leukemia.
AB - Acute myeloid leukemia (AML) is characterized by clinical and biological
heterogeneity. Despite the advances in our understanding of its pathobiology, the
chemotherapy-directed management has remained largely unchanged in the past 40
years. However, various novel agents have demonstrated clinical activity, either
as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab)
or in combination with standard induction/consolidation at diagnosis and with
salvage regimens at relapse. The classes of agents described in this review
include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic
modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors,
bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase
receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as
well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors,
and aminopeptidase inhibitors. These agents are actively undergoing clinical
investigation alone or in combination with available chemotherapy.
PMID- 28420417
TI - Do images of a personalised future body shape help with weight loss? A randomised
controlled study.
AB - BACKGROUND: This randomised controlled study evaluated a computer-generated
future self-image as a personalised, visual motivational tool for weight loss in
adults. METHODS: One hundred and forty-five people (age 18-79 years) with a Body
Mass Index (BMI) of at least 25 kg/m2 were randomised to receive a hard copy
future self-image at recruitment (early image) or after 8 weeks (delayed image).
Participants received general healthy lifestyle information at recruitment and
were weighed at 4-weekly intervals for 24 weeks. The image was created using an
iPad app called 'Future Me'. A second randomisation at 16 weeks allocated either
an additional future self-image or no additional image. RESULTS: Seventy-four
participants were allocated to receive their image at commencement, and 71 to the
delayed-image group. Regarding to weight loss, the delayed-image group did
consistently better in all analyses. Twenty-four recruits were deemed non
starters, comprising 15 (21%) in the delayed-image group and 9 (12%) in the early
image group (chi2(1) = 2.1, p = 0.15). At 24 weeks there was a significant change
in weight overall (p < 0.0001), and a difference in rate of change between groups
(delayed-image group: -0.60 kg, early-image group: -0.42 kg, p = 0.01). Men lost
weight faster than women. The group into which participants were allocated at
week 16 (second image or not) appeared not to influence the outcome (p = 0.31).
Analysis of all completers and withdrawals showed a strong trend over time (p <
0.0001), and a difference in rate of change between groups (delayed-image: -0.50
kg, early-image: -0.27 kg, p = 0.0008). CONCLUSION: One in five participants in
the delayed-image group completing the 24-week intervention achieved a clinically
significant weight loss, having received only future self-images and general
lifestyle advice. Timing the provision of future self-images appears to be
significant, and promising for future research to clarify their efficacy. TRIAL
REGISTRATION: Australian Clinical Trials Registry, identifier:
ACTRN12613000883718 . Registered on 8 August 2013.
PMID- 28420418
TI - Adult muscle-derived stem cells engraft and differentiate into insulin-expressing
cells in pancreatic islets of diabetic mice.
AB - BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose
homeostasis and their deficiency results in impaired insulin production leading
to severe diabetic diseases. Here, we investigated the potential of a population
of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to
differentiate in vitro into beta cells when transplanted as undifferentiated stem
cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured
MDSC spontaneously differentiated into insulin-expressing islet-like cell
clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry
under the control of an insulin promoter. Differentiated clusters of beta-like
cells co-expressed insulin with the transcription factors Pdx1, Nkx2.2, Nkx6.1,
and MafA, and secreted significant levels of insulin in response to glucose
challenges. In vivo, undifferentiated MDSC injected into streptozotocin (STZ)
treated mice engrafted within 48 h specifically to damaged pancreatic islets and
were shown to differentiate and express insulin 10-12 days after injection. In
addition, injection of MDSC into hyperglycemic diabetic mice reduced their blood
glucose levels for 2-4 weeks. CONCLUSION: These data show that MDSC are capable
of differentiating into mature pancreatic beta islet-like cells, not only upon
culture in vitro, but also in vivo after systemic injection in STZ-induced
diabetic mouse models. Being nonteratogenic, MDSC can be used directly by
systemic injection, and this potential reveals a promising alternative avenue in
stem cell-based treatment of beta-cell deficiencies.
PMID- 28420419
TI - Optimizing veteran-centered prostate cancer survivorship care: study protocol for
a randomized controlled trial.
AB - BACKGROUND: Although prostate cancer is the most common cancer among veterans
receiving care in the Veterans Health Administration (VA), more needs to be done
to understand and improve survivorship care for this large population. This
study, funded by VA Health Services Research & Development (HSR&D), seeks to
address the need to improve patient-centered survivorship care for veterans with
prostate cancer. METHODS/DESIGN: This is a two-armed randomized controlled trial
(RCT) with a target enrollment of up to 325 prostate cancer survivors per study
arm (total anticipated n = 600). Patients will be recruited from four VA sites.
Patient eligibility criteria include age range of 40-80 years, one to ten years
post-treatment, and currently experiencing prostate cancer symptom burden. We
will compare the "Building Your New Normal" program, a personally-tailored
automated telephone symptom management intervention for improving symptom self
management to usual care enhanced with a non-tailored newsletter about symptom
management. Primary outcomes include changes in symptom burden, bother, and
health services utilization at five and 12 months after enrollment. Secondary
outcomes include long-term psychosocial outcomes (e.g. subjective health,
perceived cancer control). We will use multivariable regression analysis to
evaluate the impact of the intervention on primary and secondary outcomes. We
will conduct a process evaluation to understand the effective intervention
components and explore possibilities for broader implementation and
dissemination. DISCUSSION: Our central hypothesis is that intervention group
participants will have improved and more confident symptom self-management and
prostate cancer quality of life following the intervention and that these
outcomes will translate to more efficient use of health services. The study
results will provide much needed information about how to optimize the quality of
care, and life, of veteran prostate cancer survivors. TRIAL REGISTRATION:
ClinicalTrials.gov ID NCT01900561 ; Registered on 22 July 2013.
PMID- 28420420
TI - Distribution of ticks infesting ruminants and risk factors associated with high
tick prevalence in livestock farms in the semi-arid and arid agro-ecological
zones of Pakistan.
AB - BACKGROUND: Tick infestation is the major problem for animal health that causes
substantial economic losses, particularly in tropical and subtropical countries.
To better understand the spatial distribution of tick species and risk factors
associated with tick prevalence in livestock in Pakistan, ticks were counted and
collected from 471 animals, including 179 cattle, 194 buffaloes, 80 goats and 18
sheep, on 108 livestock farms in nine districts, covering both semi-arid and arid
agro-ecological zones. RESULTS: In total, 3,807 ticks representing four species
were collected: Hyalomma anatolicum (n = 3,021), Rhipicephalus microplus (n =
715), Hyalomma dromedarii (n = 41) and Rhipicephalus turanicus (n = 30). The
latter species is reported for the first time from the study area. Rhipicephalus
microplus was the predominant species in the semi-arid zone, whereas H.
anatolicum was the most abundant species in the arid zone. The overall proportion
of tick-infested ruminants was 78.3% (369/471). It was highest in cattle (89.9%),
followed by buffaloes (81.4%), goats (60.0%) and sheep (11.1%). The median tick
burden significantly differed among animal species and was highest in cattle
(median 58), followed by buffaloes (median 38), goats (median 19) and sheep
(median 4.5). Female animals had significantly higher tick burdens than males
and, in large ruminants, older animals carried more ticks than younger animals.
The intensity of infestation was significantly lower in indigenous animals
compared to exotic and crossbred cows. Analysis of questionnaire data revealed
that the absence of rural poultry, not using any acaricides, traditional rural
housing systems and grazing were potential risk factors associated with a higher
tick prevalence in livestock farms. CONCLUSION: Absence of rural poultry, not
performing acaricide treatments, traditional rural housing systems and grazing
were important risk factors associated with higher tick prevalence in livestock
farms. Age, gender, breed and animal species significantly affected the intensity
of tick infestation. This report also describes the presence of R. turanicus in
the Punjab Province of Pakistan for the first time. The outcomes of this study
will be useful in the planning of integrated control strategies for ticks and
tick-borne diseases in Pakistan.
PMID- 28420421
TI - Analysis of 100,000 human cancer genomes reveals the landscape of tumor
mutational burden.
AB - BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of
sensitivity to immune checkpoint inhibitors and has been shown to be more
significantly associated with response to PD-1 and PD-L1 blockade immunotherapy
than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The
distribution of TMB and the subset of patients with high TMB has not been well
characterized in the majority of cancer types. METHODS: In this study, we compare
TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB
measured by exome sequencing and simulate the expected variance in TMB when
sequencing less than the whole exome. We then describe the distribution of TMB
across a diverse cohort of 100,000 cancer cases and test for association between
somatic alterations and TMB in over 100 tumor types. RESULTS: We demonstrate that
measurements of TMB from comprehensive genomic profiling are strongly reflective
of measurements from whole exome sequencing and model that below 0.5 Mb the
variance in measurement increases significantly. We find that a subset of
patients exhibits high TMB across almost all types of cancer, including many rare
tumor types, and characterize the relationship between high TMB and
microsatellite instability status. We find that TMB increases significantly with
age, showing a 2.4-fold difference between age 10 and age 90 years. Finally, we
investigate the molecular basis of TMB and identify genes and mutations
associated with TMB level. We identify a cluster of somatic mutations in the
promoter of the gene PMS2, which occur in 10% of skin cancers and are highly
associated with increased TMB. CONCLUSIONS: These results show that a CGP assay
targeting ~1.1 Mb of coding genome can accurately assess TMB compared with
sequencing the whole exome. Using this method, we find that many disease types
have a substantial portion of patients with high TMB who might benefit from
immunotherapy. Finally, we identify novel, recurrent promoter mutations in PMS2,
which may be another example of regulatory mutations contributing to
tumorigenesis.
PMID- 28420422
TI - High resolution melting: a useful field-deployable method to measure dhfr and
dhps drug resistance in both highly and lowly endemic Plasmodium populations.
AB - BACKGROUND: Emergence and spread of drug resistance to every anti-malarial used
to date, creates an urgent need for development of sensitive, specific and field
deployable molecular tools for detection and surveillance of validated drug
resistance markers. Such tools would allow early detection of mutations in
resistance loci. The aim of this study was to compare common population
signatures and drug resistance marker frequencies between two populations with
different levels of malaria endemicity and history of anti-malarial drug use:
Tanzania and Senegal. This was accomplished by implementing a high resolution
melting assay to study molecular markers of drug resistance as compared to
polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP)
methodology. METHODS: Fifty blood samples were collected each from a lowly
malaria endemic site (Senegal), and a highly malaria endemic site (Tanzania) from
patients presenting with uncomplicated Plasmodium falciparum malaria at clinic.
Data representing the DHFR were derived using both PCR-RFLP and HRM assay; while
genotyping data representing the DHPS were evaluated in Senegal and Tanzania
using HRM. Msp genotyping analysis was used to characterize the multiplicity of
infection in both countries. RESULTS: A high prevalence of samples harbouring
mutant DHFR alleles was observed in both population using both genotyping
techniques. HRM was better able to detect mixed alleles compared to PCR/RFLP for
DHFR codon 51 in Tanzania; and only HRM was able to detect mixed infections from
Senegal. A high prevalence of mutant alleles in DHFR (codons 51, 59, 108) and
DHPS (codon 437) were found among samples from Senegal while no mutations were
observed at DHPS codons 540 and 581, from both countries. Overall, the frequency
of samples harbouring either a single DHFR mutation (S108N) or double mutation in
DHFR (C59R/S108N) was greater in Senegal compared to Tanzania. CONCLUSION: Here
the results demonstrate that HRM is a rapid, sensitive, and field-deployable
alternative technique to PCR-RFLP genotyping that is useful in populations
harbouring more than one parasite genome (polygenomic infections). In this study,
a high levels of resistance polymorphisms was observed in both dhfr and dhps,
among samples from Tanzania and Senegal. A routine monitoring by molecular
markers can be a way to detect emergence of resistance involving a change in the
treatment policy.
PMID- 28420423
TI - A comprehensive evaluation of an ELISA for the diagnosis of the two most common
ascarids in chickens using plasma or egg yolks.
AB - BACKGROUND: Classical faecal egg counts (FEC) provide less reliable diagnostic
information for nematode infections in chickens. We developed an ELISA based on
Ascaridia galli antigens and tested two hypotheses, as follows: (i) IgY
antibodies developed against A. galli will also be useful to identify Heterakis
gallinarum infections, and (ii) circulating antibodies stored in egg yolks are as
good as plasma samples, so a non-invasive diagnosis is possible. The aim of this
study, therefore, was to compare the diagnostic accuracy of the ELISA system with
FEC, using both plasma and egg yolks from experimentally infected hens. In
addition, naturally infected animals were evaluated to validate the assay.
RESULTS: The assay quantified large differences (P < 0.001) in plasma or in egg
yolk IgY concentrations between infected and uninfected animals in two
experiments, each performed with either of the nematode species. The assay
performed with high accuracy as quantified with the area under the ROC curve
(AUC) values of > 0.90 for both nematodes using either plasma or egg yolks.
Sensitivity of the assay was 94 and 93% with plasma and egg yolk samples,
respectively, whereas FEC yielded in a sensitivity of 84% in A. galli experiment.
Total test accuracy of the assay with plasma samples (AUC = 0.99) tended to be
higher (P = 0.0630) than FEC (AUC = 0.92) for A. galli, while the assay with
either sample matrix performed similar to FEC (AUC >= 0.91) for H. gallinarum.
Among the three tests, the FECs correlated better with A. galli burden than the
ELISA. Although 90% of naturally infected hens were correctly identified by the
ELISA, 45% of the infected hens tested negative with FEC, indicating the validity
of the higher test accuracy of the ELISA. CONCLUSIONS: Antigens of A. galli can
be used successfully to identify H. gallinarum-infected animals, indicating that
chickens develop cross-reactive antibodies against the two closely related
species. Egg yolks are as informative as plasma samples, so that animal welfare
friendly sampling is possible. Although the assay with plasma samples reveals
qualitative information of higher quality than FECs on the infection status of
naturally infected birds, the latter is still a better tool to assess the
intensity of A. galli but not of H. gallinarum infections.
PMID- 28420424
TI - A novel lncRNA uc.134 represses hepatocellular carcinoma progression by
inhibiting CUL4A-mediated ubiquitination of LATS1.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies
worldwide, and tumor recurrence and metastasis are major factors that contribute
to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known
to regulate different tumorigenic processes, and a growing body of evidence
indicates that Hippo kinase signaling is inactivated in many cancers. However,
the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly
understood. METHODS: Using a lncRNA microarray, we identified a novel lncRNA,
uc.134, whose expression was significantly decreased in the highly aggressive HCC
cell line HCCLM3 compared with MHCC97L cells. Furthermore, we evaluated uc.134
expression in clinical samples using in situ hybridization (ISH) and quantitative
real-time polymerase chain reaction (qRT-PCR) analysis. The full-length
transcript of uc.134 was confirmed using rapid amplification of cDNA ends (RACE)
analyses. To investigate the biological function of uc.134, we performed gain-of
function and loss-of-function studies both in vitro and in vivo. The underlying
mechanisms of uc.134 in HCC were investigated using RNA pulldown, RNA
immunoprecipitation, ubiquitination assays, Western blotting, mRNA microarray
analyses, and qRT-PCR analyses. RESULTS: The ISH assay revealed that uc.134
expression was significantly decreased in 170 paraffin-embedded samples from
patients with HCC compared with adjacent tissues and uc.134 expression directly
correlated with patient prognosis. Furthermore, we defined a 1867-bp full-length
transcript of uc.134 using 5'- and 3'-RACE analysis. The overexpression of uc.134
inhibited HCC cell proliferation, invasion, and metastasis in vitro and in vivo,
whereas the knockdown of uc.134 produced the opposite results. Furthermore, we
confirmed that uc.134 (1408-1867 nt) binds to CUL4A (592-759 aa region) and
inhibits its nuclear export. Moreover, we demonstrated that uc.134 inhibits the
CUL4A-mediated ubiquitination of LATS1 and increases YAPS127 phosphorylation to
silence the target genes of YAP. Finally, a positive correlation between uc.134,
LATS1, and pYAPS127 was confirmed in 90 paraffin-embedded samples by ISH and
immunohistochemical staining. CONCLUSIONS: Our study identifies that a novel
lncRNA, uc.134, represses hepatocellular carcinoma progression by inhibiting the
CUL4A-mediated ubiquitination of LATS1 and increasing YAPS127 phosphorylation.
The use of this lncRNA may offer a promising treatment approach by inhibiting YAP
and activating Hippo kinase signaling.
PMID- 28420425
TI - Acceleration of tendon-bone healing of anterior cruciate ligament graft using
intermittent negative pressure in rabbits.
AB - BACKGROUND: The purpose of this study was to test effects of negative pressure on
tendon-bone healing after reconstruction of anterior cruciate ligament (ACL) in
rabbits. METHODS: Hind legs of 24 New Zealand White rabbits were randomly
selected as negative pressure group and the contralateral hind legs as control.
Reconstruction of the ACL was done. Joints of the negative pressure side were
placed with drainage tubes connecting the micro-negative pressure aspirator.
Control side was placed with ordinary drainage tubes. Drainage tubes on both
sides were removed at the same time 5 days after operation. After 6 weeks, joint
fluid was drawn to detect the expression levels of interleukin-1beta (IL-1beta)
and tumor necrosis factor-alpha (TNF-alpha); at the same time, femur-ligament
tibia complex was obtained to determine tendon graft tension and to observe the
histomorphology, blood vessels of the tendon-bone interface, and expression of
vascular endothelial growth factor (VEGF). RESULTS: The maximum load breakage of
tendon graft was significantly greater in the negative pressure group than in the
control group (P < 0.05). Histological studies of the tendon-bone interface found
that there was more new bone formation containing chondroid cells and aligned
connective tissue in the negative pressure group than in the control group.
Expression of VEGF was higher in the negative pressure group than in the control
group (P < 0.01). Content of IL-1beta and TNF-alpha in synovial fluid is lower in
the negative pressure group than in the control group (P < 0.01). CONCLUSIONS:
Intermittent negative pressure plays an active role in tendon-bone healing and
creeping substitution of ACL reconstruction in the rabbits.
PMID- 28420426
TI - Genotypes of SLC22A4 and SLC22A5 regulatory loci are predictive of the response
of chronic myeloid leukemia patients to imatinib treatment.
AB - BACKGROUND: Through high-throughput next-generation sequencing of promoters of
solute carrier and ATP-binding cassette genes, which encode drug transporters, we
aimed to identify SNPs associated with the response to imatinib administered for
first-line treatment of patients with chronic myeloid leukemia. METHODS: In
silico analysis using publicly available databases was done to select the SLC and
ABC genes and their promoters for the next-generation sequencing. SNPs associated
with the imatinib response were identified using Fisher's exact probability tests
and subjected to the linkage disequilibrium analyses with regulatory loci of
concerned genes. We analyzed cumulative achievement of major molecular response
and probability of event free survival in relation to identified SNP genotypes in
129 CML patients and performed multivariate analysis for determination of
genotypes as independent predictors of outcome. Gene expression analysis of eight
cell lines naturally carrying different genotypes was performed to outline an
impact of genotypes on the gene expression. RESULTS: We observed significant
differences in the frequencies of the rs460089-GC and rs460089-GG (SLC22A4)
genotypes among rs2631365-TC (SLC22A5) genotype carriers that were associated
with optimal and non-optimal responses, respectively. Loci rs460089 and rs2631365
were in highly significant linkage disequilibrium with 12 regulatory loci in
introns of SLC22A4 and SLC22A5 encoding imatinib transporters. Genotype
association analysis with the response to imatinib indicated that rs460089-GC
carriers had a significantly higher probability of achieving a stable major
molecular response (BCR-ABL1 transcript level below or equal to 0.1% in the
international scale). In contrast, the rs460089-GG represented a risk factor for
imatinib failure, which was significantly higher in rs460089-GG_rs2631365-TC
carriers. CONCLUSIONS: This exploratory study depicted potentially important
genetic markers predicting outcome of imatinib treatment, which may be helpful
for tailoring therapy in clinical practice.
PMID- 28420427
TI - Isolation and characterization of equine native MSC populations.
AB - BACKGROUND: In contrast to humans in which mesenchymal stem/stromal cell (MSC)
therapies are still largely in the clinical trial phase, MSCs have been used
therapeutically in horses for over 15 years, thus constituting a valuable
preclinical model for humans. In human tissues, MSCs have been shown to originate
from perivascular cells, namely pericytes and adventitial cells, which are
identified by the presence of the cell surface markers CD146 and CD34,
respectively. In contrast, the origin of MSCs in equine tissues has not been
established, preventing the isolation and culture of defined cell populations in
that species. Moreover, a comparison between perivascular CD146+ and CD34+ cell
populations has not been performed in any species. METHODS: Immunohistochemistry
was used to identify adventitial cells (CD34+) and pericytes (CD146+) and to
determine their localization in relation to MSCs in equine tissues. Isolation of
CD34+ (CD34+/CD146-/CD144-/CD45-) and CD146+ (CD146+/CD34-/CD144-/CD45-) cell
fractions from equine adipose tissue was achieved by fluorescence-activated cell
sorting. The isolated cell fractions were cultured and analyzed for the
expression of MSC markers, using qPCR and flow cytometry, and for the ability to
undergo trilineage differentiation. Angiogenic properties were analyzed in vivo
using a chorioallantoic membrane (CAM) assay. RESULTS: Both CD34+ and CD146+
cells displayed typical MSC features, namely growth in uncoated tissue culture
dishes, clonal growth when seeded at low density, expression of typical MSC
markers, and multipotency shown by the capacity for trilineage differentiation.
Of note, CD146+ cells were distinctly angiogenic compared with CD34+ and non
sorted cells (conventional MSCs), demonstrated by the induction of blood vessels
in a CAM assay, expression of elevated levels of VEGFA and ANGPT1, and
association with vascular networks in cocultures with endothelial cells,
indicating that CD146+ cells maintain a pericyte phenotype in culture.
CONCLUSION: This study reports for the first time the successful isolation and
culture of CD146+ and CD34+ cell populations from equine tissues.
Characterization of these cells evidenced their distinct properties and MSC-like
phenotype, and identified CD146+ cells as distinctly angiogenic, which may
provide a novel source for enhanced regenerative therapies.
PMID- 28420428
TI - Significant heterogeneity in Wolbachia copy number within and between populations
of Onchocerca volvulus.
AB - BACKGROUND: Wolbachia are intracellular bacteria found in arthropods and several
filarial nematode species. The filarial Wolbachia have been proposed to be
involved in the immunopathology associated with onchocerciasis. Higher Wolbachia
to-nematode ratios have been reported in the savannah-ecotype compared to the
forest-ecotype, and have been interpreted as consistent with a correlation
between Wolbachia density and disease severity. However, factors such as
geographic stratification and ivermectin drug exposure can lead to significant
genetic heterogeneity in the nematode host populations, so we investigated
whether Wolbachia copy number variation is also associated with these underlying
factors. METHODS: Genomic DNA was prepared from single adult nematodes
representing forest and savannah ecotypes sampled from Togo, Ghana, Cote d'Ivoire
and Mali. A qPCR assay was developed to measure the number of Wolbachia genome(s)
per nematode genome. Next-generation sequencing (NGS) was also used to measure
relative Wolbachia copy number, and independently verify the qPCR assay. RESULTS:
Significant variation was observed within the forest (range: 0.02 to 452.99;
median: 10.58) and savannah (range: 0.01 to 1106.25; median: 9.10) ecotypes,
however, no significant difference between ecotypes (P = 0.645) was observed;
rather, strongly significant Wolbachia variation was observed within and between
the nine study communities analysed (P = 0.021), independent of ecotype. Analysis
of ivermectin-treated and untreated nematodes by qPCR showed no correlation (P =
0.869); however, an additional analysis of a subset of the nematodes by qPCR and
NGS revealed a correlation between response to ivermectin treatment and Wolbachia
copy number (P = 0.020). CONCLUSIONS: This study demonstrates that extensive
within and between population variation exists in the Wolbachia content of
individual adult O. volvulus. The origin and functional significance of such
variation (up to ~ 100,000-fold between worms; ~10 to 100-fold between
communities) in the context of the proposed mutualistic relationship between the
worms and the bacteria, and between the presence of Wolbachia and clinical
outcome of infection, remains unclear. These data do not support a correlation
between Wolbachia copy number and forest or savannah ecotype, and may have
implications for the development of anti-Wolbachia drugs as a macrofilaricidal
treatment of onchocerciasis. The biological significance of a correlation between
variation in Wolbachia copy number and ivermectin response remains unexplained.
PMID- 28420429
TI - DEPTOR maintains plasma cell differentiation and favorably affects prognosis in
multiple myeloma.
AB - BACKGROUND: The B cell maturation process involves multiple steps, which are
controlled by relevant pathways and transcription factors. The understanding of
the final stages of plasma cell (PC) differentiation could provide new insights
for therapeutic strategies in multiple myeloma (MM). Here, we explore the role of
DEPTOR, an mTOR inhibitor, in the terminal differentiation of myeloma cells, and
its potential impact on patient survival. METHODS: The expression level of DEPTOR
in MM cell lines and B cell populations was measured by real-time RT-PCR, and/or
Western blot analysis. DEPTOR protein level in MM patients was quantified by
capillary electrophoresis immunoassay. RNA interference was used to downregulate
DEPTOR in MM cell lines. RESULTS: DEPTOR knockdown in H929 and MM1S cell lines
induced dedifferentiation of myeloma cells, as demonstrated by the upregulation
of PAX5 and BCL6, the downregulation of IRF4, and a clear reduction in cell size
and endoplasmic reticulum mass. This effect seemed to be independent of mTOR
signaling, since mTOR substrates were not affected by DEPTOR knockdown.
Additionally, the potential for DEPTOR to be deregulated in MM by particular
miRNAs was investigated. The ectopic expression of miR-135b and miR-642a in
myeloma cell lines substantially diminished DEPTOR protein levels, and caused
dedifferentiation of myeloma cells. Interestingly, the level of expression of
DEPTOR protein in myeloma patients was highly variable, the highest levels being
associated with longer progression-free survival. CONCLUSIONS: Our results
demonstrate for the first time that DEPTOR expression is required to maintain
myeloma cell differentiation and that high level of its expression are associated
with better outcome. Primary samples used in this study correspond to patients
entered into GEM2010 trial (registered at www.clinicaltrials.gov as #NCT01237249,
4 November 2010).
PMID- 28420430
TI - Chronic stress induces CD99, suppresses autophagy, and affects spontaneous
adipogenesis in human bone marrow stromal cells.
AB - BACKGROUND: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent
cells with a high constitutive level of autophagy and low expression of CD99.
Under certain conditions, MSCs may develop tumorigenic properties. However, these
transformation-induced conditions are largely unknown. Recently, we have
identified an association between Hsp70, a main participant in cellular stress
response and tumorigenesis, and CD99. Preliminary observations had revealed
upregulation of both proteins in stressed long-term cultured MSCs. And so we
hypothesized that CD99 is implicated in stress-induced mechanisms of cellular
transformation in MSCs. Hence, we investigated the effects of prolonged stress on
MSCs and the role of CD99 and autophagy in their survival. METHODS: Human
telomerase reverse transcriptase (hTERT) overexpressing immortalized MSCs and
primary bone marrow stromal cells were used to investigate the influence of long
term serum deprivation and hypoxia on growth and differentiation of MSCs. Cell
proliferation and apoptosis were evaluated using flow cytometry, differentiation
capabilities of MSCs were assessed by immunohistochemical staining followed by
microscopic examination. CD99, Hsp70 expression were analyzed using flow
cytometry, western blotting, and reverse transcriptase polymerase chain reaction.
Autophagy was explored with specific inhibitors using cell morphology examination
and western blotting. RESULTS: Chronic stress factors are able to change the
morphology of MSCs and to inhibit spontaneous differentiation into adipocyte
lineage. Furthermore, CD99 elevation and downregulation of p53 and p21
accompanied defective autophagy, which is usually associated with tumor
formation. We found that inhibition of autophagy by chloroquine promoted cell
detachment and modulated CD99 expression level whereas incorporation of CD99
recombinant protein into the cells suppressed autophagy. CONCLUSIONS: Obtained
results provide a model for chronic stress-induced transformation of MSCs via
CD99 and may therefore be highly relevant to mesenchymal tumorigenesis.
PMID- 28420431
TI - Injuries in extreme sports.
AB - Extreme sports (ES) are usually pursued in remote locations with little or no
access to medical care with the athlete competing against oneself or the forces
of nature. They involve high speed, height, real or perceived danger, a high
level of physical exertion, spectacular stunts, and heightened risk element or
death.Popularity for such sports has increased exponentially over the past two
decades with dedicated TV channels, Internet sites, high-rating competitions, and
high-profile sponsors drawing more participants.Recent data suggest that the risk
and severity of injury in some ES is unexpectedly high. Medical personnel
treating the ES athlete need to be aware there are numerous differences which
must be appreciated between the common traditional sports and this newly
developing area. These relate to the temperament of the athletes themselves, the
particular epidemiology of injury, the initial management following injury,
treatment decisions, and rehabilitation.The management of the injured extreme
sports athlete is a challenge to surgeons and sports physicians. Appropriate
safety gear is essential for protection from severe or fatal injuries as the
margins for error in these sports are small.The purpose of this review is to
provide an epidemiologic overview of common injuries affecting the extreme
athletes through a focus on a few of the most popular and exciting extreme
sports.
PMID- 28420432
TI - Elevated Gab2 induces tumor growth and angiogenesis in colorectal cancer through
upregulating VEGF levels.
AB - BACKGROUND: Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves
as a critical signaling amplifier downstream of tyrosine kinase receptors. Our
previous study has shown that Gab2 induces epithelial-to-mesenchymal transition
(EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of
Gab2 in CRC growth and angiogenesis remains unclear. METHODS: The expression of
vascular endothelial growth factor (VEGF) in different colorectal tissues was
detected by immunohistochemistry and qRT-PCR to evaluate its correlation with
Gab2. Lentiviral vectors bearing Gab2 gene and its small interfering RNAs were
constructed and transfected into CRC cell lines. The effects of Gab2 on the cell
proliferation in vitro and tumorigenesis in vivo, were examined via CCK-8 assay,
colony formation assay as well as tumorigenicity assay respectively. Moreover, to
assess its potential role in tumor growth and angiogenesis, the expression of
Ki67, CD34 and vascular endothelial growth factor receptor-2 (VEGFR2) were
detected by immunohistochemistry in CRC cells tumors. Finally, we evaluated the
impact of Gab2 on the expression of c-Myc and VEGF, and the probable effect of
mechanistic targeted extracellular signal-regulated kinase (ERK) pathway in
suppressing tumor growth and angiogenesis. RESULTS: Up-regulation of Gab2
expression was found to be positively correlated with VEGF in CRC tissues.
Exogenous expression of Gab2 obviously promoted, whereas silencing of Gab2
inhibited, proliferation and clone formation of human CRC cells in vitro. Of
note, Gab2 enhanced tumorigenesis and tumor growth in mouse xenografts with high
Ki67 expression, and led to an increased vessel density with strong CD34 and
VEGFR2 activity. In addition, elevated Gab2 expression obviously up-regulated the
expression of VEGF, and stimulated the activation of its downstream genes, ERK1/2
and c-Myc in CRC cells. Instead, down-regulated Gab2 expression significantly
reduced the levels of VEGF, and inhibited the transduction of ERK/c-Myc pathway.
Finally, we revealed that mechanistic target of mitogen-activated protein kinase
(MEK) could attenuate Gab2-induced tumor growth and angiogenesis via altering
VEGF and c-Myc levels. CONCLUSIONS: The results from our study suggest that Gab2
promotes intestinal tumor growth and angiogenesis through upregulation of VEGF
expression mediated by the MEK/ERK/c-Myc pathway.
PMID- 28420433
TI - Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen
degradation via upregulation of MMP-9 in rat uterine scars.
AB - BACKGROUND: Severe injuries of the uterus may trigger uterine scar formation,
ultimately leading to infertility or obstetrical complications. To date, few
methods have adequately solved the problem of collagen deposition in uterine
scars. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown great
promise in clinical applications. The objective of this study was to investigate
the effect of a scaffold/UC-MSCs construct on collagen degradation and functional
regeneration in rat uterine scars following full-thickness excision of uterine
walls. METHODS: In order to establish a rat model of uterine scars, the uterine
wall of approximately 1.0 cm in length and 0.5 cm in width (one-third of the
uterine circumference) was excised from each uterine horn. A total of 128 scarred
uterine horns from 64 rats were randomly assigned to four groups, including a PBS
group (n = 32 uterine horns), scaffold group (n = 32 uterine horns), UC-MSCs
group (n = 32 uterine horns) and scaffold/UC-MSCs group (n = 32 uterine horns) to
investigate the effect of different treatments on the structure and function of
uterine scars. PBS, degradable collagen fibres, UC-MSCs or UC-MSCs mixed with
gelatinous degradable collagen fibres were injected into four pre-marked points
surrounding each uterine scar, respectively. At days 30 and 60 post
transplantation, a subset of rats (n = 8 uterine horns) from each group was
euthanized and serial sections of uterine tissues containing the operative region
were prepared. Haematoxylin-eosin staining, Masson's trichrome staining, and
immunohistochemical staining for MMP-2, MMP-9, alpha-SMA and vWF were performed.
Finally, another subset of rats (n = 16 uterine horns) from each group was mated
with male rats at day 60 post-transplantation and euthanized 18 days after the
presence of vaginal plugs to check numbers, sizes and weights of fetuses, as well
as sites of implantation. RESULTS: The scaffold/UC-MSCs group exhibited obvious
collagen degradation compared with the other three groups. At day 60 post
transplantation, the number of MMP-9-positive cells in the scaffold/UC-MSCs group
(25.96 +/- 3.63) was significantly higher than that in the PBS group (8.19 +/-
1.61, P < 0.01), the scaffold group (7.25 +/- 2.17, P < 0.01) and the UC-MSCs
group (8.31 +/- 2.77, P < 0.01). The pregnancy rate in the scaffold/UC-MSCs group
(10/16) was also significantly higher than that in the PBS group (2/16, P <
0.017), the scaffold group (1/16, P < 0.017) and the UC-MSCs group (3/16, P <
0.017). CONCLUSIONS: The scaffold/UC-MSCs system facilitated collagen degradation
in uterine scars via upregulation of MMP-9, which was secreted by transplanted UC
MSCs, and promoted regeneration of the endometrium, myometrium and blood vessels
in uterine scars. Furthermore, the scaffold/UC-MSCs-treated uterine scars showed
nearly complete restoration of receptive fertility.
PMID- 28420435
TI - Comparison of the mechanical properties of different skin sites for auricular and
nasal reconstruction.
AB - BACKGROUND: Autologous and synthetic nasal and auricular frameworks require skin
coverage. The surgeon's decides on the appropriate skin coverage for
reconstruction based on colour matching, subcutaneous tissue thickness, expertise
and experience. One of the major complications of placing subcutaneous implants
is the risk of extrusion (migration through the skin) and infection. However,
knowledge of lessening the differential between the soft tissue and the framework
can have important implications for extrusion. This study compared the mechanical
properties of the skin commonly used as skin sites for the coverage in auricular
and nasal reconstruction. METHODS: Using ten fresh human cadavers, the tensile
Young's Modulus of the skin from the forehead, forearm, temporoparietal, post
auricular and submandibular neck was assessed. The relaxation rate and absolute
relaxation level was also assessed after 90 min of relaxation. RESULTS: The
submandibular skin showed the greatest Young's elastic modulus in tension of all
regions (1.28 MPa +/-0.06) and forearm showed the lowest (1.03 MPa +/-0.06). The
forehead demonstrated greater relaxation rates among the different skin regions
(7.8 MPa-07 +/- 0.1). The forearm showed the lowest rate of relaxation (4.74 MPa
07 +/- 0.1). The forearm (0.04 MPa +/-0.004) and submandibular neck skin (0.04
MPa +/-0.005) showed similar absolute levels of relaxation, which were
significantly greater than the other skin regions (p < 0.05). CONCLUSIONS: This
study provides an understanding into the biomechanical properties of the skin of
different sites allowing surgeons to consider this parameter when trying to
identify the optimal skin coverage in nasal and auricular reconstruction.
PMID- 28420434
TI - The neuroprotective effects of human bone marrow mesenchymal stem cells are dose
dependent in TNBS colitis.
AB - BACKGROUND: The incidence of inflammatory bowel diseases (IBD) is increasing
worldwide with patients experiencing severe impacts on their quality of life. It
is well accepted that intestinal inflammation associates with extensive damage to
the enteric nervous system (ENS), which intrinsically innervates the
gastrointestinal tract and regulates all gut functions. Hence, treatments
targeting the enteric neurons are plausible for alleviating IBD and associated
complications. Mesenchymal stem cells (MSCs) are gaining wide recognition as a
potential therapy for many diseases due to their immunomodulatory and
neuroprotective qualities. However, there is a large discrepancy regarding
appropriate cell doses used in both clinical trials and experimental models of
disease. We have previously demonstrated that human bone marrow MSCs exhibit
neuroprotective and anti-inflammatory effects in a guinea-pig model of 2,4,6
trinitrobenzene-sulfonate (TNBS)-induced colitis; but an investigation into
whether this response is dose-dependent has not been conducted. METHODS: Hartley
guinea-pigs were administered TNBS or sham treatment intra-rectally. Animals in
the MSC treatment groups received either 1 * 105, 1 * 106 or 3 * 106 MSCs by
enema 3 hours after induction of colitis. Colon tissues were collected 72 hours
after TNBS administration to assess the effects of MSC treatments on the level of
inflammation and damage to the ENS by immunohistochemical and histological
analyses. RESULTS: MSCs administered at a low dose, 1 * 105 cells, had little or
no effect on the level of immune cell infiltrate and damage to the colonic
innervation was similar to the TNBS group. Treatment with 1 * 106 MSCs decreased
the quantity of immune infiltrate and damage to nerve processes in the colonic
wall, prevented myenteric neuronal loss and changes in neuronal subpopulations.
Treatment with 3 * 106 MSCs had similar effects to 1 * 106 MSC treatments.
CONCLUSIONS: The neuroprotective effect of MSCs in TNBS colitis is dose
dependent. Increasing doses higher than 1 * 106 MSCs demonstrates no further
therapeutic benefit than 1 * 106 MSCs in preventing enteric neuropathy associated
with intestinal inflammation. Furthermore, we have established an optimal dose of
MSCs for future studies investigating intestinal inflammation, the enteric
neurons and stem cell therapy in this model.
PMID- 28420436
TI - Autophagy mediates the beneficial effect of hypoxic preconditioning on bone
marrow mesenchymal stem cells for the therapy of myocardial infarction.
AB - BACKGROUND: Stem cell therapy has emerged as a promising therapeutic strategy for
myocardial infarction (MI). However, the poor viability of transplanted stem
cells hampers their therapeutic efficacy. Hypoxic preconditioning (HPC) can
effectively promote the survival of stem cells. The aim of this study was to
investigate whether HPC improved the functional survival of bone marrow
mesenchymal stem cells (BM-MSCs) and increased their cardiac protective effect.
METHODS: BM-MSCs, isolated from Tg(Fluc-egfp) mice which constitutively express
both firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP),
were preconditioned with HPC (1% O2) for 12 h, 24 h, 36 h, and 48 h,
respectively, followed by 24 h of hypoxia and serum deprivation (H/SD) injury.
RESULTS: HPC dose-dependently increased the autophagy in BM-MSCs. However, the
protective effects of HPC for 24 h are most pronounced. Moreover, hypoxic
preconditioned BM-MSCs (HPCMSCs) and nonhypoxic preconditioned BM-MSCs (NPCMSCs)
were transplanted into infarcted hearts. Longitudinal in vivo bioluminescence
imaging (BLI) and immunofluorescent staining revealed that HPC enhanced the
survival of engrafted BM-MSCs. Furthermore, HPCMSCs significantly reduced
fibrosis, decreased apoptotic cardiomyocytes, and preserved heart function.
However, the beneficial effect of HPC was abolished by autophagy inhibition with
3-methyladenine (3-MA) and Atg7siRNA. CONCLUSION: This study demonstrates that
HPC may improve the functional survival and the therapeutic efficiencies of
engrafted BM-MSCs, at least in part through autophagy regulation. Hypoxic
preconditioning may serve as a promising strategy for optimizing cell-based
cardiac regenerative therapy.
PMID- 28420437
TI - Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration.
AB - An intronic GGGGCC expansion in C9orf72 is the most common known cause of both
frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS).
The repeat expansion leads to the generation of sense and antisense repeat RNA
aggregates and dipeptide repeat (DPR) proteins, generated by repeat-associated
non-ATG translation. The arginine-rich DPR proteins poly(glycine-arginine or GR)
and poly(proline-arginine or PR) are potently neurotoxic and can localise to the
nucleolus when expressed in cells, resulting in enlarged nucleoli with disrupted
functionality. Furthermore, GGGGCC repeat RNA can bind nucleolar proteins in
vitro. However, the relevance of nucleolar stress is unclear, as the arginine
rich DPR proteins do not localise to the nucleolus in C9orf72-associated FTLD/ALS
(C9FTLD/ALS) patient brain. We measured nucleolar size in C9FTLD frontal cortex
neurons using a three-dimensional, volumetric approach. Intriguingly, we found
that C9FTLD brain exhibited bidirectional nucleolar stress. C9FTLD neuronal
nucleoli were significantly smaller than control neuronal nucleoli. However,
within C9FTLD brains, neurons containing poly(GR) inclusions had significantly
larger nucleolar volumes than neurons without poly(GR) inclusions. In addition,
expression of poly(GR) in adult Drosophila neurons led to significantly enlarged
nucleoli. A small but significant increase in nucleolar volume was also observed
in C9FTLD frontal cortex neurons containing GGGGCC repeat-containing RNA foci.
These data show that nucleolar abnormalities are a consistent feature of C9FTLD
brain, but that diverse pathomechanisms are at play, involving both DPR protein
and repeat RNA toxicity.
PMID- 28420438
TI - Distance traveled for Medicaid-covered abortion care in California.
AB - BACKGROUND: Access to abortion care in the United States is limited by the
availability of abortion providers and their geographic distribution. We aimed to
assess how far women travel for Medicaid-funded abortion in California and
identify disparities in access to abortion care. METHODS: We obtained data on all
abortions reimbursed by the fee-for-service California state Medicaid program
(Medi-Cal) in 2011 and 2012 and examined distance traveled to obtain abortion
care by several demographic and abortion-related factors. Mixed-effects
multivariable logistic regression models were constructed to examine factors
associated with traveling 50 miles or more. County-level t-tests and linear
regressions were conducted to examine the effects of a Medi-Cal abortion provider
in a county on overall and urban/rural differences in utilization. RESULTS: 11.9%
(95% CI: 11.5-12.2%) of women traveled 50 miles or more. Women obtaining second
trimester or later abortions (21.7%), women obtaining abortions at hospitals
(19.9%), and rural women (51.0%) were most likely to travel 50 miles or more.
Across the state, 28 counties, home to 10% of eligible women, did not have a
facility routinely providing Medi-Cal-covered abortions. CONCLUSIONS: Efforts are
needed to expand the number of abortion providers that accept Medi-Cal. This
could be accomplished by increasing Medi-Cal reimbursement rates, increasing the
types of providers who can provide abortions, and expanding the use of
telemedicine. If national trends in declining unintended pregnancy and abortion
rates continue, careful attention should be paid to ensure that reduced demand
does not lead to greater disparities in geographic and financial access to
abortion care by ensuring that providers accepting Medicaid payment are available
and widely distributed.
PMID- 28420439
TI - Fragile X syndrome: a review of clinical and molecular diagnoses.
AB - BACKGROUND: Fragile X Syndrome (FXS) is the second cause of intellectual
disability after Down syndrome and the most prevalent cause of intellectual
disability in males, affecting 1:5000-7000 men and 1:4000-6000 women. It is
caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more
than 99% of individuals have a CGG expansion (>200 triplets) in the 5' UTR of the
gene, and FMR1 mutations and duplication/deletion are responsible for the
remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather
the current clinical and molecular knowledge about FXS to provide clinicians with
a tool to guide the initial assessment and follow-up of FXS and to offer to
laboratory workers and researchers an update about the current diagnostic
procedures. DISCUSSION: FXS is a well-known condition; however, most of the
studies thus far have focused on neuropsychiatric features. Unfortunately, some
of the available studies have limitations, such as the paucity of patients
enrolled or bias due to the collection of the data in a single-country
population, which may be not representative of the average global FXS population.
In recent years, insight into the adult presentation of the disease has
progressively increased. Pharmacological treatment of FXS is essentially symptom
based, but the growing understanding of the molecular and biological mechanisms
of the disease are paving the way to targeted therapy, which may reverse the
effects of FMRP deficiency and be a real cure for the disease itself, not just
its symptoms. CONCLUSIONS: The clinical spectrum of FXS is wide, presenting not
only as an isolated intellectual disability but as a multi-systemic condition,
involving predominantly the central nervous system but potentially affecting any
apparatus. Given the relative high frequency of the condition and its complex
clinical management, FXS appears to have an important economic and social burden.
PMID- 28420440
TI - Immune response after autologous hematopoietic stem cell transplantation in type
1 diabetes mellitus.
AB - BACKGROUND: This study explored the details of the immune response after
autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1
diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18
patients with type 1 diabetes mellitus were taken at baseline and 12 months after
AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and
secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T
helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in
PBMC culture supernatants were assessed. RESULTS: Compared with patients
receiving insulin-only treatment, the patients receiving AHSCT treatment showed
better residual C-peptide secretion, lower anti-GAD titers and less exogenous
insulin dosages after 12 months of follow-up. AHSCT treatment was associated with
significantly reduced Th1 and Th17 cell proportions as well as decreased IFN
gamma, IL-2, IL-12p40 and IL-17A levels in the PBMC culture supernatants (all P <
0.05). Although there was no significant Treg cell expansion after AHSCT
treatment, we observed increased IL-10, TGF-beta and Foxp3 mRNA expression and
increased TGF-beta levels. However, we found no significant changes in the T-cell
subpopulations after insulin treatment, except for higher IL-12p40 mRNA
expression and a lower proportion of Treg cells. CONCLUSIONS: AHSCT treatment was
associated with decreased expansion and function of Th1 and Th17 cells, which may
explain the better therapeutic effect of AHSCT compared with the traditional
intensive insulin therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00807651 .
Registered 18 December 2008.
PMID- 28420441
TI - Autologous bone marrow-derived cell transplantation in decompensated alcoholic
liver disease: what is the impact on liver histology and gene expression
patterns?
AB - BACKGROUND: Liver stem cell therapy (SCT) has been suggested as a promising means
to improve liver regeneration in advanced liver disease. However, data from
trials are heterogeneous, with no systematic histological evaluation. The aim of
this study is to specifically analyze the effect of autologous SCT on liver
regeneration and on gene expression changes. METHODS: Individuals in the
randomized controlled trial of SCT in alcoholic hepatitis with paired liver
biopsies were included (n = 58). Immunohistochemistry (Ki67, K7, and CD68), in
situ hybridization (SPINK1), and global gene expression analysis were performed
on liver biopsies (30 control patients and 28 patients with transarterial
administration of bone marrow-derived stem cells) both at baseline and after 4
weeks of follow-up. RESULTS: No difference between the two groups could be
observed regarding the proliferative hepatocyte number, proliferative K7-positive
cells, or total K7-positive cells at the 4-week follow-up liver biopsy. However,
patients who received SCT showed a more important liver macrophagic expansion as
compared to standard treatment. Transcriptome data revealed changes in genes
linked with inflammation (CD68 and SAA), regeneration (SPINK1 and HGF), fibrosis
(COL1A1), and stem cells (CD45). No changes in gene pathways involved in liver
growth and cell cycle proteins were evident. SPINK1 mRNA was present by in situ
hybridization at week 4 in SCT patients in the liver parenchyma areas adjacent to
macrophage recruitment and liver cell proliferation. CONCLUSIONS: The analysis of
liver tissue after SCT demonstrated an expansion of macrophages concurrent with
an upregulated expression of genes involved in inflammatory and regenerative
pathways. With the negative results from the clinical trial, the impact of the
SCT has to be interpreted as weak, and it is not able to modify the clinical
course of this severe liver disease.
PMID- 28420442
TI - Updated systematic review: associations between proximity to animal feeding
operations and health of individuals in nearby communities.
AB - OBJECTIVE: The objective of this review was to update a systematic review of
associations between living near an animal feeding operation (AFO) and human
health. METHODS: The MEDLINE(r) and MEDLINE(r) In-Process, Centre for
Agricultural Biosciences Abstracts, and Science Citation Index databases were
searched. Reference lists of included articles were hand-searched. Eligible
studies reported exposure to an AFO and an individual-level human health outcome.
Two reviewers performed study selection and data extraction. RESULTS: The search
returned 3702 citations. Sixteen articles consisting of 10 study populations were
included in the analysis. The health outcomes were lower and upper respiratory
tracts, MRSA, other infectious disease, neurological, psychological,
dermatological, otologic, ocular, gastrointestinal, stress and mood, and other
non-infectious health outcomes. Most studies were observational and used
prevalence measures of outcome. An association between Q fever risk and proximity
to goat production was reported. Other associations were unclear. Risk of bias
was serious or critical for most exposure-outcome associations. Multiplicity
(i.e., a large number of potentially correlated outcomes and exposures assessed
on the same study subjects) was common in the evidence base. CONCLUSIONS: Few
studies reported an association between surrogate clinical outcomes and AFO
proximity for respiratory tract-related outcomes. There were no consistent dose
response relationships between surrogate clinical outcome and AFO proximity. A
new finding was that Q fever in goats is likely associated with an increased Q
fever risk in community members. The review results for the non-respiratory
health outcomes were inconclusive because only a small number of studies were
available or the between-study results were inconsistent. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42014010521.
PMID- 28420443
TI - Tau phosphorylation induced by severe closed head traumatic brain injury is
linked to the cellular prion protein.
AB - Studies in vivo and in vitro have suggested that the mechanism underlying
Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between
the cellular prion protein (PrPC) and amyloid-beta oligomers (Abetao). This PrPC
Abetao complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P
Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD
transgenic mice lacking PrPC accumulate Abeta, but show normal survival and no
loss of spatial learning and memory suggesting that PrPC functions downstream of
Abetao production but upstream of intracellular toxicity within neurons. Since AD
and traumatic brain injury (TBI)-linked chronic traumatic encephalopathy are
tauopathies, we examined whether similar mechanistic pathways are responsible for
both AD and TBI pathophysiologies. Using transgenic mice expressing different
levels of PrPC, our studies investigated the influence and necessity of PrPC on
biomarker (total-tau [T-Tau], P-Tau, GFAP) levels in brain and blood as measured
biochemically following severe TBI in the form of severe closed head injury
(sCHI). We found that following sCHI, increasing levels of T-Tau and P-Tau in the
brain were associated with the PrPC expression levels. A similar relationship
between PrPC expression and P-Tau levels following sCHI were found in blood in
the absence of significant T-Tau changes. This effect was not seen with GFAP
which increased within 24 h following sCHI and progressively decreased by the 7
day time point regardless of the PrPC expression levels. Changes in the levels of
all biomarkers were independent of gender. We further enhanced and expanded the
quantitation of brain biomarkers with correlative studies using
immunohisochemistry. We also demonstrate that a TBI-induced calpain
hyperactivation is not required for the generation of P-Tau. A relationship was
demonstrated between the presence/absence of PrPC, the levels of P-Tau and
cognitive dysfunction. Our studies suggest that PrPC is important in mediating
TBI related pathology.
PMID- 28420444
TI - Case report: ACTH-secreting pituitary carcinoma metastatic to the liver in a
patient with a history of atypical pituitary adenoma and Cushing's disease.
AB - BACKGROUND: Pituitary carcinoma is a rare entity requiring the presence of
metastasis to confirm its malignant potential. We report a case of pituitary
carcinoma and discuss the diagnosis and management of this lesion in relation to
the existing literature. CASE PRESENTATION: The patient is a 51-year-old woman
with Cushing's disease and intact adrenal glands who was diagnosed with
metastatic pituitary carcinoma to the liver, 29 months after initial resection of
an ACTH-secreting primary atypical pituitary adenoma (APA). Prior to detection of
this metastasis the patient underwent repeat resection and radiotherapy for
residual cavernous sinus disease. The metastatic lesion was detected by interval
surveillance of serum ACTH and 24-hour urine cortisol, which despite stable
pituitary MRI, were significantly elevated. These abnormalities prompted a PET
scan that demonstrated hypermetabolic liver parenchyma, which was suspicious for
metastasis on abdominal MRI. An ultrasound-guided liver biopsy demonstrated nests
of moderately-differentiated cells with intermediate-sized, monotonous nuclei,
distinct nucleoli, and abundant basophilic cytoplasm, confirmed by
immunohistochemistry to represent metastatic pituitary carcinoma. The liver
lesion was subsequently successfully removed by wedge resection. One year later,
the patient's residual cavernous sinus disease grew markedly, and she was placed
on dual-agent chemotherapy consisting of oral temozolomide and capecitabine, with
stabilization of her intracranial disease to present, although liver metastases
recurred. CONCLUSIONS: Pituitary carcinoma is a rare entity impossible to
recognize as a primary tumor because its diagnosis by definition requires the
presence of metastasis. Maintaining awareness of the entity and its precursor
lesion APA is essential for its accurate pathologic diagnosis and appropriate
management.
PMID- 28420445
TI - Investigation of the association between the TCF7L2 rs7903146 (C/T) gene
polymorphism and obesity in a Cameroonian population: a pilot study.
AB - OBJECTIVE: This study aimed at investigating the association between the
rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian
population. METHOD: This was a case-control pilot study including 61 obese and 61
non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure,
fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T)
polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP), and genotypes were
correlated with clinical and biological parameters. RESULTS: The T allele was
predominant in the study population with a frequency of 93%. No statistically
significant difference was however observed between the genotypic (p = 0.50) and
allelic frequencies (p = 0.58) of obese and non-obese subjects. Comparison of
clinical and biochemical parameters of C allele carriers (CX = CC + CT) with
those of TT genotype showed that there was no significant difference between the
lipid profile of these two groups. CONCLUSION: The rs7903146 (C/T) polymorphism
of the TCF7L2 gene might not be associated with obesity in the Cameroonian
population.
PMID- 28420446
TI - Immune resistance and tolerance strategies in malaria vector and non-vector
mosquitoes.
AB - BACKGROUND: The Anopheles gambiae complex consists of species that vary greatly
in their capacity to transmit malaria. The mosquito immune system has been
identified as a key factor that can influence whether Plasmodium infection
establishes within the mosquito vector. This study was designed to investigate
the immune responses of An. coluzzii, An. arabiensis and An. quadriannulatus
mosquitoes. The first two mosquito species are major vectors of malaria in sub
Saharan Africa, while the third is thought to be a non-vector. METHODS: All three
mosquito species were reared in mixed cultures. Their capacity to eliminate P.
berghei and regulate midgut bacteria was examined. RESULTS: Our results revealed
large differences in mosquito resistance to P. berghei. In all three mosquito
species, immune reactions involving the complement system were triggered when the
number of parasites that mosquitoes were challenged with exceeded a certain
level, i.e. immune tolerance threshold. This threshold was markedly lower in An.
quadriannulatus compared to An. coluzzii and An. arabiensis. We also demonstrated
that the level of immune tolerance to P. berghei infection in the haemolymph is
inversely correlated with the level of immune tolerance to microbiota observed in
the midgut lumen after a blood meal. The malaria non-vector mosquito species, An.
quadriannulatus was shown to have a much higher level of tolerance to microbiota
in the midgut than An. coluzzii. CONCLUSIONS: We propose a model whereby an
increased tolerance to microbiota in the mosquito midgut results in lower
tolerance to Plasmodium infection. In this model, malaria non-vector mosquito
species are expected to have increased immune resistance in the haemocoel,
possibly due to complement priming by microbiota elicitors. We propose that this
strategy is employed by the malaria non-vector mosquito, An. quadriannulatus,
while An. coluzzii has reduced tolerance to bacterial infection in the midgut and
consequently reduced immune resistance to Plasmodium infection at the haemocoel
level. An in-depth understanding of the molecular mechanisms regulating immune
tolerance versus resistance in different mosquito vectors of malaria could guide
the design of new vector and disease control strategies.
PMID- 28420449
TI - Interpersonal harm aversion as a necessary foundation for morality: A
developmental neuroscience perspective.
AB - Growing evidence from developmental psychology and social neuroscience emphasizes
the importance of third-party harm aversion for constructing morality. A
sensitivity to interpersonal harm emerges very early in ontogeny, as reflected in
both the capacity for implicit social evaluation and an aversion for antisocial
agents. Yet it does not necessarily entail avoidance toward inflicting pain to
others. Later, an understanding that harmful actions cause suffering emerges,
followed by an integration of rules that can depend on social contexts and
cultures. These developmental findings build on a burgeoning literature, which
suggests that the fundamental nature of moral and social cognition, including
their motivational and hedonic value, lies in general computational processes
such as attention, approach-avoidance, social valuation, and decision making
rather than in fully distinct, dedicated neural regions for morality. Bridging
the gap between cognition and behaviors and the requisite affective,
motivational, and cognitive mechanisms, a developmental neuroscience approach
enriches our understanding of the emergence of morality.
PMID- 28420447
TI - CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs
cartilage in mice with destabilized medial meniscus.
AB - BACKGROUND: Osteoarthritis (OA) of the knee involves degeneration of articular
cartilage of the diarthrodial joints. Current treatment options temporarily
relieve the joint pain but do not restore the lost cartilage. We recently
designed a novel bone morphogenetic protein receptor type I (BMPRI) mimetic
peptide, CK2.1, that activates BMPRIa signaling in the absence of bone
morphogenetic protein (BMP). Our previous research demonstrated that CK2.1
induced chondrogenesis in vitro and in vivo; however, it is unknown if CK2.1
restores damaged articular cartilage in vivo. In this study, we demonstrate that
CK2.1 induced articular cartilage (AC) repair in an OA mouse model. METHODS: We
designed hyaluronic acid (HA)-based hydrogel particles (HGPs) that slowly release
CK2.1. HGP-CK2.1 particles were tested for chondrogenic potency on pluripotent
mesenchymal stem cells (C3H10T1/2 cells) and locally injected into the intra
articular capsule in mice with cartilage defects. C57BL/6J mice were operated on
to destabilize the medial meniscus and these mice were kept for 6 weeks after
surgery to sustain OA-like damage. Mice were then injected via the intra
articular capsule with HGP-CK2.1; 4 weeks after injection the mice were
sacrificed and their femurs were analyzed for cartilage defects. RESULTS:
Immunohistochemical analysis of the cartilage demonstrated complete repair of the
AC compared to sham-operated mice. Immunofluorescence analysis revealed collagen
type IX production along with collagen type II in the AC of mice injected with
HGP-CK2.1. Mice injected with phosphate-buffered saline (PBS) and HGP alone had
greater collagen type X and osteocalcin production, in sharp contrast to those
injected with HGP-CK2.1, indicating increased chondrocyte hypertrophy.
CONCLUSIONS: Our results demonstrate that the slow release HGP-CK2.1 drives
cartilage repair without the induction of chondrocyte hypertrophy. The peptide
CK2.1 could be a powerful tool in understanding the signaling pathways
contributing to the repair process, and also may be used as a potential
therapeutic for treating degenerative cartilage diseases such as OA.
PMID- 28420448
TI - Association of cognitive function and liability to addiction with childhood
herpesvirus infections: A prospective cohort study.
AB - Liability to substance use disorder (SUD) is largely nonspecific to particular
drugs and is related to behavior dysregulation, including reduced cognitive
control. Recent data suggest that cognitive mechanisms may be influenced by
exposure to neurotropic infections, such as human herpesviruses. In this study,
serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1
(HSV-1), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) as well as
Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174
daughters of fathers with or without SUD. Its relationships with a cognitive
characteristic (IQ) in childhood and with risk for SUD in adulthood were examined
using correlation, regression, survival, and path analyses. Exposure to HSV-1,
EBV, and T. gondii in males and females, and CMV in males, was associated with
lower IQ. Independent of that relationship, EBV in females and possibly in males,
and CMV and possibly HSV-1 in females were associated with elevated risk for SUD.
Therefore, childhood neurotropic infections may influence cognitive development
and risk for behavior disorders such as SUD. The results may point to new avenues
for alleviating cognitive impairment and SUD risk.
PMID- 28420451
TI - What leads to high antipsychotic dosing in forensic patients with schizophrenia?
AB - Earlier findings suggest that forensic schizophrenia patients are treated with
higher doses of antipsychotics. This practice-based specificity is insufficiently
studied, and clinicians' motives regarding this practice remain poorly
understood. In this editorial, the authors provide their data on treatment of
forensic schizophrenia patients and identify characteristics of psychopathology
and previous types of behaviors, including suicidal attempts, as potential
reasons for the practice. They also emphasize that "these previous acts" often
took place years ago, and suggest that current or recent aggression is unlikely
the main reason for dosing, but rather the clinicians' intention to maintain
"must remain unaggressive" condition. Therefore, the authors suggest new ideas
that may contribute to a better understanding of the specific prescribing
patterns in the forensic population and hope that these ideas would be
implemented in further well-designed prospective studies.
PMID- 28420450
TI - What side effects are problematic for patients prescribed antipsychotic
medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.
AB - BACKGROUND: Capturing service users' perspectives can highlight additional and
different concerns to those of clinicians, but there are no up to date, self
report psychometrically sound measures of side effects of antipsychotic
medications. Aim To develop a psychometrically sound measure to identify
antipsychotic side effects important to service users, the Maudsley Side Effects
(MSE) measure. METHOD: An initial item bank was subjected to a Delphi exercise (n
= 9) with psychiatrists and pharmacists, followed by service user focus groups
and expert panels (n = 15) to determine item relevance and language. Feasibility
and comprehensive psychometric properties were established in two samples (N43
and N50). We investigated whether we could predict the three most important side
effects for individuals from their frequency, severity and life impact. RESULTS:
MSE is a 53-item measure with good reliability and validity. Poorer mental and
physical health, but not psychotic symptoms, was related to side-effect burden.
Seventy-nine percent of items were chosen as one of the three most important
effects. Severity, impact and distress only predicted 'putting on weight' which
was more distressing, more severe and had more life impact in those for whom it
was most important. CONCLUSIONS: MSE is a self-report questionnaire that
identifies reliably the side-effect burden as experienced by patients.
Identifying key side effects important to patients can act as a starting point
for joint decision making on the type and the dose of medication.
PMID- 28420452
TI - Fathering moderates the effects of maternal depression on the family process.
AB - Maternal depression negatively impacts children's development, yet few studies
have focused on fathering and the family process in cases of maternal depression.
A community cohort of married/cohabitating women was recruited on the second
postbirth day (N = 1,983) and maternal depression repeatedly assessed across the
first year and again at 6 years to form two cohorts: mothers chronically
depressed from birth to 6 (N = 46) and nondepressed controls (N = 103). At 6
years, mother-child, father-child, and family interactions were observed. In
families of depressed mothers, both mother and father exhibited lower sensitivity
and higher intrusiveness, and children displayed lower social engagement during
interactions with mother and father. Fathering moderated the effects of maternal
depression on the family process. When fathers showed low sensitivity, high
intrusiveness, and provided little opportunities for child social engagement, the
family process was less cohesive, implying a decrease in the family's harmonious,
warm, and collaborative style. However, in cases of high father sensitivity, low
intrusiveness, and increased child engagement, the family process was unaffected
by maternal depression. Findings describe both comparability and compensatory
mechanisms in the effects of fathering on family life when maternal care is
deficient, highlight the buffering role of fathers, and underscore the importance
of father-focused interventions when mothers are depressed.
PMID- 28420453
TI - Golden Years or Retirement Fears? Private Pension Inequality Among Canada's
Immigrants.
AB - Currently, many immigrants are disqualified from Canada's public pension scheme
because of residency requirements. In addition, decades of low income and labour
market exclusion prohibit many Canadian immigrants from building adequate private
pension savings throughout their working life. Together, these factors present
serious concerns for immigrant seniors' economic well-being. Using Canadian
census data spanning a twenty-year period (1991-2011), we find that income from
personal savings plans and investments has declined sharply for both native-born
and immigrant Canadians, with recent immigrant cohorts faring worst. However,
since 1991, native-born and immigrant men living in Canada for 40-plus years had
major gains in private employer pensions (Registered Pension Plans; [RPPs]). Yet
RPP income for all other immigrant cohorts remained stable or declined during
these decades. Thus, the data demonstrate a worrisome growing private savings gap
between native-born men and all others in Canada, with newer immigrants and women
faring worst.
PMID- 28420455
TI - Nutrient profiling for product reformulation: public health impact and benefits
for the consumer.
AB - The food industry holds great potential for driving consumers to adopt healthy
food choices as (re)formulation of foods can improve the nutritional quality of
these foods. Reformulation has been identified as a cost-effective intervention
in addressing non-communicable diseases as it does not require significant
alterations of consumer behaviour and dietary habits. Nutrient profiling (NP),
the science of categorizing foods based on their nutrient composition, has
emerged as an essential tool and is implemented through many different profiling
systems to guide reformulation and other nutrition policies. NP systems should be
adapted to their specific purposes as it is not possible to design one system
that can equally address all policies and purposes, e.g. reformulation and
labelling. The present paper discusses some of the key principles and
specificities that underlie a NP system designed for reformulation with the
example of the Nestle nutritional profiling system. Furthermore, the impact of
reformulation at the level of the food product, dietary intakes and public health
are reviewed. Several studies showed that food and beverage reformulation, guided
by a NP system, may be effective in improving population nutritional intakes and
thereby its health status. In order to achieve its maximum potential and modify
the food environment in a beneficial manner, reformulation should be implemented
by the entire food sector. Multi-stakeholder partnerships including governments,
food industry, retailers and consumer associations that will state concrete time
bound objectives accompanied by an independent monitoring system are the
potential solution.
PMID- 28420456
TI - Impaired Comprehension of Speed Verbs in Parkinson's Disease.
AB - OBJECTIVES: A wealth of studies provide evidence for action simulation during
language comprehension. Recent research suggests such action simulations might be
sensitive to fine-grained information, such as speed. Here, we present a crucial
test for action simulation of speed in language by assessing speed comprehension
in patients with Parkinson's disease (PD). Based on the patients' motor deficits,
we hypothesized that the speed of motion described in language would modulate
their performance in semantic tasks. Specifically, they would have more
difficulty processing language about relatively fast speed than language about
slow speed. METHODS: We conducted a semantic similarity judgment task on fast and
slow action verbs in patients with PD and age-matched healthy controls.
Participants had to decide which of two verbs most closely matched a target word.
RESULTS: Compared to controls, PD patients were slower making judgments about
fast action verbs, but not for judgments about slow action verbs, suggesting
impairment in processing language about fast action. Moreover, this impairment
was specific to verbs describing fast action performed with the hand.
CONCLUSIONS: Problems moving quickly lead to difficulties comprehending language
about moving quickly. This study provides evidence that speed is an important
part of action representations. (JINS, 2017, 23, 412-420).
PMID- 28420454
TI - Genetic and environmental influences on the codevelopment among borderline
personality disorder traits, major depression symptoms, and substance use
disorder symptoms from adolescence to young adulthood.
AB - Although borderline personality disorder (BPD) traits decline from adolescence to
adulthood, comorbid psychopathology such as symptoms of major depressive disorder
(MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt
this normative decline. Using a longitudinal sample of female twins (N = 1,763),
we examined if levels of BPD traits were correlated with changes in MDD, AUD, and
DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model
examined the contributions of genetic and environmental factors to the
relationships between developmental components of these phenotypes. Higher BPD
trait levels predicted a greater rate of increase in AUD and DUD symptoms, and
higher AUD and DUD symptoms predicted a slower rate of decline of BPD traits from
ages 14 to 24. Common genetic influences accounted for the associations between
BPD traits and each disorder, as well as the interrelationships of AUD and DUD
symptoms. Both genetic and nonshared environmental influences accounted for the
correlated levels between BPD traits and MDD symptoms, but solely environmental
influences accounted for the correlated changes between the two over time.
Results indicate that higher levels of BPD traits may contribute to an earlier
onset and faster escalation of AUD and DUD symptoms, and substance use problems
slow the normative decline in BPD traits. Overall, our data suggests that
primarily genetic influences contribute to the comorbidity between BPD features
and substance use disorder symptoms. We discuss our data in the context of two
major theories of developmental psychopathology and comorbidity.
PMID- 28420457
TI - Are impairments in emotion recognition a core feature of callous-unemotional
traits? Testing the primary versus secondary variants model in children.
AB - The role of environmental adversity in the development of high callous
unemotional (CU) traits in children is controversial. Evidence speaks to the
traits being largely independent of adversity; however, recent data shows that
those with high CU traits and high adversity and/or high anxiety might differ in
important ways from those with no such history. We tested this using emotion
recognition (ER) skills. We tested whether maltreatment history and anxiety
levels moderated the relationship between level of CU traits and ER skills in N =
364 children with behavioral problems who were 3 to 16 years old. As
hypothesised, in the full sample, the relationship between CU traits and ER
differed according to maltreatment history, such that CU traits were associated
with poorer recognition for those with zero or negligible history of
maltreatment. This moderation of the CU-ER relationship by maltreatment was
inconsistent across subgroups, however, and for the cohort utilizing youth self
report of maltreatment, high CU traits were associated with poor ER in those with
lower anxiety levels. Maltreatment history and/or anxiety levels can identify
different emotional impairments associated with high CU traits, and the
impairments might be characteristic of "primary" high CU traits defined as
occurring independently of maltreatment and/or high anxiety.
PMID- 28420459
TI - [Comparison between the international and the Japanese guidelines for the
management of sepsis and septic shock 2016].
PMID- 28420458
TI - Potentially important periods of change in the development of social and role
functioning in youth at clinical high risk for psychosis.
AB - The developmental course of daily functioning prior to first psychosis-onset
remains poorly understood. This study explored age-related periods of change in
social and role functioning. The longitudinal study included youth (aged 12-23,
mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis
(converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy
control group (n = 164). Mixed-model analyses were performed to determine age
related differences in social and role functioning. We limited our analyses to
functioning before psychosis conversion; thus, data of CHR-C participants
gathered after psychosis onset were excluded. In controls, social and role
functioning improved over time. From at least age 12, functioning in CHR was
poorer than in controls, and this lag persisted over time. Between ages 15 and
18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who
continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement
between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A
similar period of stagnation was apparent for role functioning, but to a lesser
extent (p = .007). The results remained consistent when we accounted for the time
to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in
social and role functioning in adolescence, followed by a period of further
stagnation in adulthood.
PMID- 28420460
TI - [Bone marrow mesenchymal stem cells modulated the inflammatory response by
regulating the expression of IL-4 and RAGE products in the rats with MODS].
AB - OBJECTIVE: To investigate the underlying mechanism of bone marrow mesenchymal
stem cells (BMSC) modulating the inflammatory response during the multiple organ
dysfunction syndrome (MODS), especially the expression of inflammatory cytokines,
which will provide new theoretical and experimental basis of MODS in clinic.
METHODS: BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and
cultivated, and the 4th passage were used in experimental study. According to the
random number table, 60 female SD rats were divided into three groups (n = 20 per
group): sham group, MODS group, BMSC group. MODS model in rats was induced by
lipopolysaccaride (LPS, 1 mg/kg) via femoral vein injection. Sham group was
injected with the sterile phosphate buffer saline (PBS) in the same volume. BMSC
group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation
(1*106/cells) through the tail vein. The survival rate was observed after 72
hours in each group. Abdominal aortic blood was collected for routine blood and
biochemical examination at 72 hours after operation. Protein microarray was used
to detect the related 34 inflammatory cytokines. Signal ratio was defined as the
differentially expressed factors when it was more than 2.0 or less than 0.5. And
enzyme linked immunosorbent assay (ELISA) was be applied to validate the
significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue
was harvested, then their pathological changes were observed by hematoxylin eosin
(HE) staining. RESULTS: 20, 12, 16 rats lived in sham group, MODS group and BMSC
group respectively at 72 hours after operation. Compared with the sham group, the
indicators (routine blood, liver and kidney function, myocardial enzyme) were
apparently unusual, and the heart, kidney, intestine tissue were injured
obviously in the MODS group. After BMSC administration, the organ function was
improved and tissue damaged was alleviated significantly. Protein microarray
showed that interleukin-4 (IL-4) and receptor for advanced glycation end products
(RAGE) were significantly different in 34 goal cytokines. The signal ratio change
of IL-4 was 0.397, 1.124, 2.826 respectively, and the signal ratio of RAGE was
6.197, 1.552, 0.250, respectively in MODS/sham group, BMSC/sham group, BMSC/MODS
group. ELISA validated the result that the expression level of IL-4 decreased
significantly (ng/L: 3.59+/-1.21 vs. 29.10+/-5.78) and the expression level of
RAGE increased significantly (ng/L: 1.09+/-0.04 vs. 0.11+/-0.03) in MODS group as
compared with sham group (both P < 0.05). Compared with the MODS group, the level
of IL-4 was obviously higher than that in BMSC group (ng/L: 9.59+/-2.21 vs.
3.59+/-1.21, P < 0.01), and RAGE decreased significantly (ng/L: 0.29+/-0.07 vs.
1.09+/-0.04, P < 0.05). CONCLUSIONS: BMSC administration can regulate the
expression of IL-4 and RAGE in the rats subjected to MODS. Moreover, BMSC can
promote the restoration of tissue and organ function, thus improve the survival
rate. BMSC may be the target in cell therapy for the inflammatory disease.
PMID- 28420461
TI - [alpha7 nicotinic acetylcholine receptor agonist attenuated the
lipopolysaccharide-induced inflammatory response via inhibiting the activation of
nuclear factor-KappaB].
AB - OBJECTIVE: To investigate the effects of alpha7 nicotinic acetylcholine receptor
(alpha7nAChR) on the inflammatory response induced by lipopolysaccharide (LPS) in
RAW264.7 macrophages and its molecular mechanisms. METHODS: RAW264.7 macrophages
were cultured in vitro. Inflammatory cell model was constructed by LPS
stimulation. Cells were challenged by LPS (1, 10, 100 and 500 MUg/L) for 5 hours
or 100 MUg/L LPS for 0, 2, 4, 8, 12, 24, 48 and 72 hours, and the release of
tumor necrosis factor-alpha (TNF-alpha) was detected by the enzyme linked
immunosorbent assay (ELISA). The location of alpha7nAChR was examined in RAW264.7
macrophages by immunofluorescence. Then the cell proliferation and toxicity kit
(CCK-8) was used to detect 1, 10, 100, 1?000 MUmol/L GTS-21, a alpha7nAchR
agonist, on the cell viability after LPS stimulation. ELISA was used to detect 1,
10, 100, 1?000 MUmol/L GTS-21 on the levels of TNF-alpha, interleukin 1beta (IL
1beta) after LPS stimulation. Cells were challenged with 100 ?g/L LPS and 100
?mol/L GTS-21, then, the level of high mobility group box 1 (HMGB1) was detected
by Western Blot and the intracellular location of HMGB1 and nuclear factor-KappaB
p65 (NF-KappaB p65) was tested by immunofluorescence. RESULTS: LPS increased the
level of TNF-alpha to a peak at the concentration of 100 MUg/L and at 24 hours
after stimulation. The alpha7nAChR expressed on the macrophages. The cell
viability was decreased in a dose-dependent manner [(96.2+/-1.0)%, (92.0+/-1.1)%
vs. (86.5+/-2.2)%, both P < 0.05]. Compared with the control group, the levels of
TNF-alpha and IL-1beta in the supernatant of LPS group were significantly
increased [TNF-alpha (ng/L): 453.0+/-60.6 vs. 100.8+/-3.2, IL-1beta (MUg/L):
8.21+/-0.31 vs. 0.87+/-0.16, both P < 0.05]. TNF-alpha and IL-1beta were
significantly decreased by 10 MUmol/L and 100 MUmol/L GTS-21 in a dose-dependent
manner [TNF-alpha (ng/L): 227.5+/-17.5, 81.0+/-8.8 vs. 453.0+/-60.6; IL-1beta
(MUg/L): 4.86+/-0.72, 2.32+/-0.45 vs. 8.21+/-0.31, all P < 0.05]. GTS-21
significantly reduced the expression of HMGB1 which was induced by LPS management
(gray value: 0.788+/-0.130 vs. 2.061+/-0.330, P < 0.05) and reversed LPS-induced
HMGB1 cytoplasmic transfer. GTS-21 also reversed LPS-induced nuclear
translocation of NF-KappaB p65. CONCLUSIONS: GTS-21 reduces the inflammatory
response via inhibiting the activation of NF-KappaB.
PMID- 28420462
TI - [Differential expression profile of long non-coding RNA in the lipopolysaecharide
induced inflammation of monocyte-derived macrophages].
AB - OBJECTIVE: To analyze the expression profile of long non-coding RNA (lncRNA) in
the lipopolysaecharide (LPS)-induced inflammation of monocyte-derived
macrophages. METHODS: Peripheral blood mononuclear cells were derived from
healthy donor and induced into macrophages. The macrophages were divided into
blank control group and LPS (1 mg/L) stimulated 12 hours group. Culture
supernatants and cell pellets were harvested in each group, enzyme linked
immunosorbent assay (ELISA) was used to assay the production changes of
interleukins (IL-1beta and IL-6), and tumor necrosis factor-alpha (TNF-alpha) in
the supernatant. The technique of lncRNA microarray was used to test the lncRNA
expression profile in LPS-induced inflammation of macrophages and control
macrophages. The raw data of lncRNA were pretreated for normalization. Five
lncRNA expressions were validated by real-time quantitative reverse transcription
polymerase chain reaction (qRT-PCR). Furthermore, qRT-PCR was used to detect the
expression of NR_028034 in macrophages after LPS-induced inflammation. RESULTS:
(1) The contents of IL-1beta (ng/L: 562.93+/-61.17 vs. 59.74+/-15.68), IL-6
(ng/L: 702.46+/-92.31 vs. 71.66+/-18.25) and TNF-alpha (ng/L: 794.50+/-63.89 vs.
85.12+/-22.07) in the LPS group were significantly higher than those in the blank
control group (all P < 0.01). These results indicated that the inflammatory model
of human macrophages was constructed successfully. (2) Compared with blank
control group, and 1 479 lncRNA which have more than 2 folds variation and
significant difference (P < 0.05) by statistical analysis was defined as lncRNA
with differential expression. Among these lncRNA, LPS group showed 953 up-
regulated and 526 down- regulated genes by 2 folds and 49 up- regulated and 35
down- regulated genes by 5 folds. (3) qRT-PCR results were generally consistent
with the microarray data. (4) The expression of NR_028034 was increased by
(4.41+/-0.65), (11.56+/-2.04), (18.58+/-1.36) folds compared with blank control
group at 3, 6, 12 hours after LPS stimulation (all P < 0.01). CONCLUSIONS: These
data show a significantly altered lncRNA expression profile in the LPS-induced
inflammation of monocyte-derived macrophages, suggesting that lncRNA may be
involved in regulation of macrophages inflammatory response.
PMID- 28420463
TI - [Changes of small intestinal villi microcirculation in sidestream dark-field
imaging with different target blood pressure in rabbits during endotoxin shock].
AB - OBJECTIVE: Changes of small intestine villus microcirculation perfusion in
sidestream dark-field (SDF) imaging in the rabbits during endotoxic shock after
fluid resuscitation with different target mean arterial pressure (MAP), and
evaluation of feasibility of monitoring small intestine villus microcirculation
by SDF were studied. METHODS: Sixty standard New Zealand white rabbits were
randomly divided into two groups: low target MAP group (group A, n = 30) and high
target MAP group (group B, n = 30). Fistula operation of ileum was made in vitro,
and lipopolysaccharide (LPS, 2 mg/kg) was injected to establish endotoxic shock
model. Group A was administered with the lower dose fluid resuscitation (lactated
Ringer solution, 20 mL*kg-1*h-1) for target MAP of 65 mmHg (1 mmHg = 0.133 kPa);
group B was administered with the higher dose fluid resuscitation (lactated
Ringer solution, 30 mL*kg-1*h-1) for MAP of 80 mmHg. Continuous norepinephrine
intravenous injection (0.5-1.0 MUg*kg-1*min-1) was administered only after fluid
therapy couldn't reach the target MAP. The changes of small intestine villus
microcirculation perfusion indexes such as vessels per villus (VV), proportion of
perfused villi (PPV), microvascular flow index (MFI), borders of villus score
(BVS), vessels villus score (VVS) were continuously observed and recorded before
the shock, during the shock and after fluid resuscitation using SDF imaging. The
differences of microcirculation perfusion were compared between two groups using
the specific parameter evaluation system to determine severity of villi
microcirculation and injury scores at different stages. RESULTS: VV and borders
of villus were clear and contact before shock in two groups. After shock, VV, PPV
were significantly decreased in both two groups, the borders of villus were
destroyed, MFI, BVS, VVS and the total score of villi injury microcirculation
were obviously and severely decreased. Partial blood flow of villous capillaries
after fluid resuscitation was recovered in two groups, but the perfusion of some
region was un-balanced with the outworn borders of villus. VV were rose as
compared before and after fluid resuscitation in groups A and B (vessels: 1.21+/
0.22 vs. 0.81+/-0.12, 1.54+/-0.28 vs. 0.79+/-0.13), and PPV [(31+/-4)% vs. (12+/
2)%, (38+/-5)% vs. (13+/-3)%], MFI (1.55+/-0.09 vs. 1.09+/-0.03, 1.97+/-0.11 vs.
1.05+/-0.03), VVS (points: 1.22+/-0.08 vs. 0.89+/-0.02, 2.06+/-0.15 vs. 0.90+/
0.02) and the sum of MFI, BVS, VVS (3.70+/-0.19 vs. 2.85+/-0.07, 5.01+/-0.29 vs.
2.88+/-0.08) were significant rose (all P < 0.05). The recovery of group B was
better than that of group A, and the injury score was reduced. But BVS were not
increased in both groups compared with before and after shock (points: 0.93+/
0.05 vs. 0.87+/-0.03, 0.98+/-0.09 vs. 0.93+/-0.05, both P > 0.05). CONCLUSIONS:
For the small intestine villus microcirculation perfusion, the higher target MAP
(80 mmHg) after fluid resuscitation or/and vasoconstrictor drugs usage were
probably better than the relatively lower target MAP (65 mmHg) during endotoxic
shock. SDF imaging is a very promising technique for intestinal villi
microcirculatory visualization and assessment.
PMID- 28420464
TI - [Effect of combination therapy with propofol and hydrogen-rich saline on organ
damage and cytokines in a murine model of sepsis].
AB - OBJECTIVE: To investigate the effect of combining propofol with hydrogen on organ
damage and inflammation of sepsis in cecal ligation and puncture (CLP) mice
model. METHODS: One hundred and forty male C57BL/6 mice were randomly divided
into groups (n = 28): sham group, CLP group, propofol group, H2 group, and
propofol and H2 group. The sepsis was induced by CLP operation. Mice in sham
group did the same operation with ligation and puncture. The mice of propofol
group and propofol and H2 group were given 50 mg/kg propofol through tail vein at
1 hour and 6 hours after CLP and the mice of H2 group and propofol and H2 group
were given 5 mL/kg H2-rich saline i.p. at 1 hour and 6 hours after CLP. The
survival rates were observed during 7 days in twenty mice of each group. Inferior
vena cava blood and part lung, liver and kidney tissue were collected for
detection of the concentration of tumor necrosis factor-alpha (TNF-alpha),
interleukin-1beta (IL-1beta) and high mobility group box 1 (HMGB1) at 24 hours
after CLP in the 40 animals left (each n = 8). Then, the rest tissue of lung,
liver and kidney tissue were harvested to test histopathology and histological
score. RESULTS: The 1, 2, 3, 5, 7 days survival rate of septic mice were 80%,
40%, 20%, 10%, and 0%, respectively. The survival rate of animals increased
significantly after propofol or hydrogen-rich treatment, and the combined
treatment can further increase survival rate to 90%, 75%, 60%, 55%, and 55%,
respectively. Compared with the sham group, inflammatory factors were
significantly increased in blood and organ tissues, cell degeneration, necrosis,
congestion and inflammatory cell infiltration in lung, liver and kidney, and
tissues histological scores were significantly increased. The levels of
inflammatory factors were reduced in blood and tissues, cell degeneration,
necrosis, congestion and inflammatory cell infiltration were alleviated in lung,
liver and kidney, and tissues histological scores were decreased after propofol
or hydrogen-rich treatment compared with CLP group; these indicators were further
improved in propofol and H2 group compared with propofol group or H2 group [2, 3,
5, 7-day survival rate: 75% vs. 60%, 65%; 60% vs. 50%, 50%; 55% vs. 45%, 40%; 55%
vs. 40%, 40%; blood TNF-alpha (ng/L): 367+/-74 vs. 612+/-132, 588+/-117; blood IL
1beta (ng/L): 321+/-68 vs. 502+/-95, 476+/-86; blood HMGB1 (MUg/L): 4.6+/-0.9 vs.
7.0+/-1.4, 6.8+/-1.3; lung TNF-alpha (ng/g): 307+/-70 vs. 512+/-132, 488+/-102;
lung IL-1beta (ng/g): 367+/-77 vs. 571+/-108, 466+/-89; lung HMGB1 (MUg/g): 5.1+/
1.0 vs. 7.8+/-1.7, 7.1+/-1.5; liver TNF-alpha (ng/g): 247+/-57 vs. 431+/-112,
389+/-87; liver IL-1beta (ng/g): 267+/-58 vs. 417+/-85, 399+/-76; liver HMGB1
(MUg/g): 4.2+/-1.1 vs. 7.1+/-1.6, 6.6+/-1.2; kidney TNF-alpha (ng/g): 257+/-41
vs. 480+/-89, 448+/-82; kidney IL-1beta (ng/g): 258+/-39 vs. 409+/-68, 411+/-66;
kidney HMGB1 (MUg/g): 3.9+/-0.7 vs. 6.8+/-1.2, 5.7+/-1.0; histological scores:
lung: 1.22+/-0.28 vs. 2.61+/-0.49, 2.58+/-0.44; liver: 1.38+/-0.32 vs. 2.76+/
0.51, 2.62+/-0.46; kidney: 1.19+/-0.25 vs. 2.43+/-0.41, 2.36+/-0.40; all P <
0.05]. CONCLUSIONS: Both propofol and H2 can improve the survival rate of sepsis,
reduce tissue damage and the release of cytokines, and combined application of
the two treatment was better.
PMID- 28420465
TI - [Clinical value of serum endocan and procalcitonin in early diagnosis and
prognosis evaluation of sepsis].
AB - OBJECTIVE: To investigate the clinical value of serum endocan and procalcitonin
(PCT) in early diagnosis and prognosis evaluation of sepsis. METHODS: The
patients with systemic inflammatory response syndrome (SIRS, n = 26) and sepsis
(n = 78) admitted to intensive care unit (ICU) of the Third Hospital of Hebei
Medical University from December 2014 to December 2016 were enrolled. According
to the severity of disease, the sepsis patients were divided into general sepsis
group (n = 20), severe sepsis group (n = 24), and septic shock group (n = 34).
The cases were divided into survival group (n = 55) and non-survival group (n =
23) according to 28-day mortality. The serum endocan, PCT, acute physiology and
chronic health evaluation II (APACHEII) score, and sequential organ failure
assessment (SOFA) score were recorded when the patients were admitted into ICU.
The differences in endocan, PCT, APACHEII, SOFA score between SIRS and sepsis
groups and within sepsis subgroups were compared. Spearman correlation analysis
was used to analyze the correlation between the indexes of sepsis patients.
Receiver operation characteristic curve (ROC) was used to evaluate the value of
endocan and PCT for the diagnosis and prognosis of sepsis. RESULTS: (1) Serum
endocan, PCT, APACHEII, SOFA score and 28-day mortality in the sepsis group were
significantly higher than those in the SIRS group [endocan (MUg/L): 4.28 (10.64)
vs. 1.03 (0.69), PCT (MUg/L): 3.94 (10.75) vs. 0.43 (0.39), APACHEII: 18.81+/
9.17 vs. 9.35+/-3.78, SOFA: 9.00 (7.20) vs. 4.50 (1.50), 28-day mortality: 29.49%
vs. 11.54%, all P < 0.01]. The area under the ROC curve (AUC) of endocan, PCT,
APACHEII, SOFA score for sepsis diagnosis were 0.887, 0.842, 0.822, 0.835,
respectively. When the cut-off value of endocan was 1.26 MUg/L, the sepsis
diagnostic sensitivity was 87.2% and specificity was 81.8%. When the cut-off
value of PCT was 0.75 MUg/L, the sepsis diagnostic sensitivity was 85.9% and
specificity was 81.8%. (2) With the severity of the disease increased, the index
showed an increasing trend in patients with sepsis. Serum endocan, PCT, APACHEII,
SOFA score and 28-day mortality in septic shock group were significantly higher
than those in severe sepsis group or general sepsis group [endocan (MUg/L): 13.02
(6.70) vs. 3.33 (3.05), 1.60 (0.98); PCT (MUg/L): 8.10 (17.68) vs. 5.47 (8.92),
1.57 (2.78); APACHEII: 25.00 (9.50) vs. 18.00 (9.00), 9.50 (5.75); SOFA: 13.00
(4.50) vs. 8.00 (3.00), 5.00 (3.50); 28-day mortality: 52.94% vs. 20.83%, 0%; all
P < 0.01]. There was a significantly positive correlation between endocan, PCT,
APACHEII, SOFA, indicating that the endocan and PCT can be used to assess the
severity of sepsis. (3) Serum endocan, PCT, APACHEII and SOFA score in non
survival group were significantly higher than those in the survival group
[endocan (MUg/L): 15.05 (9.23) vs. 2.32 (4.81), PCT (MUg/L): 18.40 (16.99) vs.
3.10 (6.67), APACHEII: 28.13+/-7.56 vs. 14.91+/-6.64, SOFA: 14.70+/-3.65 vs.
7.38+/-3.26, all P < 0.01]. The AUC of endocan, PCT, APACHEII, SOFA score for the
prediction of non-survival sepsis were 0.915, 0.763, 0.899, 0.930. When the cut
off value of endocan was 4.37 MUg/L, the septic death prediction sensitivity was
95.7% and specificity was 70.9%. When the cut-off value of PCT was 7.68 MUg/L,
the septic death prediction sensitivity was 65.2% and specificity was 78.2%.
CONCLUSIONS: Serum endocan is more clinically valuable than PCT in early
diagnosis and prognosis assessment of sepsis.
PMID- 28420466
TI - [Analysis of evaluation indexes for prognosis of severe burn patients with
sepsis].
AB - OBJECTIVE: To compare changes in indexes and analyze their values in prognosis of
severe burn patients with sepsis. METHODS: A retrospective analysis was
conducted. The patients with severe burn sepsis admitted to the Third Affiliated
Hospital of Soochow University from August 2014 to December 2016 were enrolled.
The blood culture was positive in the clinical diagnosis of sepsis. According to
the prognosis, the patients were divided into death group and survival group.
Their general information, vital signs, blood routine examination, serum sodium
(Na+), serum glucose (Glu), C-reactive protein (CRP) and arterial partial
pressure of carbon dioxide (PaCO2) at the time of admission and diagnosis of
sepsis as well as the level of serum procalcitonin (PCT) at admission, diagnosis
of sepsis and 1-8 days of post diagnosis were also compared. Receiver operating
characteristic curve (ROC) was used to analyze the prognostic value of each
index, and multivariate Cox regression analysis was used to analyze the influence
of each index on the survival time, and the survival curve of Kaplan-Meier was
analyzed for dead patients. RESULTS: There were 25 cases of severe burn patients
with sepsis, which were admitted to hospital within 12 hours after injury; the
time of diagnosis of burn sepsis was (14+/-6) days; 8 cases of survival; 17 cases
died, the mortality rate was 68.0%, the time from diagnosis of sepsis to death
was (28+/-14) days. The age of the death group was significantly higher than that
of the survival group (years: 41+/-12 vs. 29+/-9, t = 2.598, P = 0.016), but
there was no significant difference in the gender, total burn area, III degree
area, and the time of diagnosis of sepsis between the two groups. The platelet
count (PLT) at the diagnosis of sepsis in death group was significantly lower
than that of the survival group (*109/L: 69+/-43 vs. 180+/-108, t = -2.773, P =
0.023), and the PCT at 1-8 days of post-diagnosis in the death group was
significantly higher than that of survival group [MUg/L: 4.4 (2.2, 9.0) vs. 1.6
(0.7, 2.3), Z = -2.521, P = 0.012], but there was no significant difference in
body temperature, heart rate, white blood cell count (WBC), percentage of
neutrophils (Neu), Na+, Glu, CRP, PCT, PaCO2 at the time of admission and
diagnosis of sepsis and PLT at the time of admission between the two groups. ROC
curve analysis showed that the area under ROC curve (AUC) of age, PLT at the time
of diagnosis and PCT at 1-8 days of post-diagnosis of sepsis was 0.808, 0.779,
0.825, respectively, for predicting the prognosis of patients with severe burn
sepsis (all P < 0.05). At the cut-off age of 32, the sensitivity was 73.3% and
the specificity was 75.0%. As the cut-off of PLT was 138*109/L at the time of
diagnosis, the sensitivity was 92.3% and the specificity was 75.0%. As the cut
off of PCT was 2.39 MUg/L at 1-8 days of post-diagnosis of sepsis, the
sensitivity was 73.3% and the specificity was 87.5%. Multivariate Cox regression
analysis showed that age and PLT at the time of diagnosis were the favorable
factors for the survival time of patients with severe burn sepsis (beta value
were -1.834, -0.029, respectively, both P < 0.05). Kaplan-Meier survival analysis
for patients in the death group showed that the median survival time of patients
>=32 years old was longer than that of patients < 32 years old (days: 32 vs. 9);
18-day cumulative survival rate was significantly higher than that of patients <
32 years old [83.3% (10/12) vs. 25.0% (1/4), chi 2 = 9.705, P = 0.003].
CONCLUSIONS: Age, PLT at diagnosis of sepsis and PCT at 1-8 days after diagnosis
of sepsis could be used as prognostic indexes for severe burn patients with
sepsis.
PMID- 28420467
TI - [Study of Plasma amino acid related metabolites of septic rats using gas
chromatography-mass spectrometry].
AB - OBJECTIVE: To reveal the pathophysiological changes of sepsis, the plasma
metabonomics of septic rats was determined and differential metabolites were
determined by gas chromatography-mass spectrometry (GC-MS). METHODS: Male
Spraguee-Dawley (SD) rats about 8 weeks were randomly divided into sham group (n
= 18) and sepsis group (n = 24). Cecal ligation and puncture (CLP) was used to
build sepsis model, while cecum was kept intact only in the sham group. 6 hours
after the operation, rats were anesthetized, and blood was harvested through
heart thoracotomy. Then the plasma metabonomics was detected by GC-MS and
metabolic profile analysis was performed to find the relative differential
metabolites. RESULTS: Principal component analysis (PCA) and partial least
squares discriminant analysis (PLS-DA) showed that the metabolic profiling of the
sepsis group was significantly different from the sham group. 259 kinds of
metabolites were got by GC-MS, and 69 kinds of differential metabolites were
found between sham group and sepsis group, in which 23 differential metabolites
were related to amino acid metabolism. Compared with sham group, the contents of
putrescine, N-glutamic acid, hydroxynorvaline, 3-cyanuric acid, D-alanyl-D
alanine and urea in the plasma of septic rats increased significantly, which
ratios of sepsis/sham group were 10.876, 6.394, 2.800, 2.226, 1.323, 1.203,
respectively (all P < 0.05). On the other hand, the contents of oxygen generation
of proline, citrulline, glutamine, su-beta-hydroxy aspartic acid, citric acid, N
methyl-DL-alanine, serine, lysine, threonine, N-formyl-L-methionine, methionine,
alanine, nicotinuric acid, N-methyl-L-glutamic acid, trans-4-hydroxy-L-proline,
proline, L-glutamic acid in the plasma of septic rats decreased significantly,
which ratios of sepsis/sham group were 0.858, 0.853, 0.834, 0.816, 0.816, 0.814,
0.813, 0.801, 0.793, 0.792, 0.774, 0.766, 0.748, 0.727, 0.716, 0.674, 0.603,
respectively (all P < 0.05). CONCLUSIONS: Through the GC-MS analysis of plasma
metabonomics of septic rats, we found abnormal energy metabolism changes. The
content of amino acid in plasma might be a method to evaluate the energy
metabolism status of sepsis.
PMID- 28420468
TI - [Effect of heparin pretreatment on the level of neutrophil extracellular traps of
serum and lung tissue in septic mice].
AB - OBJECTIVE: To investigate the influence of heparin pretreatment on serum and lung
tissue level of neutrophil extracellular traps (NETs) in septic mice model and
its molecular mechanism. METHODS: Ninety male C57BL/6J mice were randomly divided
into control group (n = 30), lipopolysaccharides (LPS) group (n = 30, 30 mg/kg
LPS in 100 ?L normal saline was intraperitoneally injected) and LPS+heparin group
(n = 30, 8 U of heparin in 20 ?L normal saline was subcutaneously injected 30
minutes before the injection of LPS). Six hours later of LPS injection, blood was
collected and lung tissue was harvested. Enzyme linked immunosorbent assay
(ELISA) was used to assess the concentration of tumor necrosis factor-alpha (TNF
alpha), interleukin-6 (IL-6), and histones 2AX (H2AX), neutrophil elastase (NE),
which reflected NETs concentration. PicoGreen fluorescent dyes was used to detect
serum circulating free DNA (cf-DNA/NETs) concentration. The protein expression
levels of H2AX and NE in lung tissue were examined by Western Blot. RESULTS: The
serum concentrations of TNF-alpha, IL-6, H2AX, NE, cf-DNA/NETs, and the protein
expression levels of H2AX and NE in lung tissue of septic mice were significantly
higher than those of control group [TNF-alpha (ng/L): 133.0+/-14.1 vs. 2.7+/-1.0,
IL-6 (ng/L): 3 911.2+/-189.2 vs. 298.9+/-52.5, H2AX (ng/L): 545.5+/-40.0 vs.
21.9+/-8.3, NE (MUg/L): 6.48+/-0.12 vs. 0.47+/-0.15, cf-DNA/NETs (MUg/L): 846.3+/
137.5 vs. 152.7+/-36.4, H2AX protein (gray value): 1.14+/-0.09 vs. 0.68+/-0.04,
NE protein (gray value): 0.56+/-0.03 vs. 0.32+/-0.04, all P < 0.05]. After
heparin pretreatment, levels of serum TNF-alpha, H2AX, NE, cf-DNA/NETs, and
protein expression levels of H2AX and NE in lung tissue were significantly
reduced [TNF-alpha (ng/L): 83.2+/-7.6 vs. 133.0+/-14.1, H2AX (ng/L): 435.0+/-39.0
vs. 545.5+/-40.0, NE (MUg/L): 4.26+/-0.17 vs. 6.48+/-0.12, cf-DNA/NETs (MUg/L):
606.5+/-73.9 vs. 846.3+/-137.5, H2AX protein (gray value): 0.91+/-0.03 vs. 1.14+/
0.09, NE protein (gray value): 0.42+/-0.03 vs. 0.56+/-0.03, all P < 0.05], but no
significant change was found in IL-6 (ng/L: 3 919.9+/-166.6 vs. 3 911.2+/-189.2,
P > 0.05). CONCLUSIONS: Heparin pretreatment could significantly decrease the
level of NETs in serum and lung tissue, and can be the potential mechanism of its
organ protection in sepsis.
PMID- 28420469
TI - [Heparin reduces endothelial cell damage induced by neutrophil extracellular
traps].
AB - OBJECTIVE: Clarify the effect of neutrophil extracellular traps (NETs) on
endothelial cell injury, and investigate whether the heparin can exert a
protective effect on endothelial cells by reducing the endothelial cell injury
induced by NETs. METHODS: Neutrophils (PMN) were obtained from healthy human
peripheral blood by Percoll-Histopaque density gradient centrifugation, and was
stimulated with phorbol ester (PMA) to induce NETs. The qualitative and
quantitative analysis of NETs was detected by immunofluorescence staining
combined with fluorescence detector. The NETs were used to induce human umbilical
vein endothelial cells (HUVEC) in vitro. Recombinant DNA hydrolytic enzymes
(rhDNase) and heparin intervention were added respectively. The activity of HUVEC
was measured by methyl thiazolyl tetrazolium (MTT) method after 6 hours. RESULTS:
PMA can stimulate PMN to produce NETs. Immunofluorescence staining showed the
formation of reticular formation around the PMN. The concentration of cell-free
DNA in the supernatant of PMN stimulated by PMA was significant increased
compared with the control group through the detection of PicoGreen fluorescent
labeling instrument (2 hours: 119.62+/-14.83 vs. 24.27+/-0.67, 4 hours: 146.67+/
21.24 vs. 28.35+/-2.98, both P < 0.05). Application of NETs to stimulate the
HUVEC, cell damage was dose dependent and inhibition rate increased gradually.
The endothelial cell inhibition induced by NETs can be antagonized after adding
rhDNase [10 MUg/L NETs: (8.65+/-0.51)% vs. (10.99+/-0.35)%, 20 MUg/L NETs:
(14.85+/-0.43)% vs. (16.85+/-0.49)%, 30 MUg/L NETs: (26.06+/-3.51)% vs. (27.54+/
0.62)%, all P < 0.05]. Heparin with different concentrations were added into the
experimental group (0.01, 0.1, 1, 10 kU/L). We found that the endothelial cell
inhibition rate decreased compared with control group [10 MUg/L NETs: (8.96+/
0.70)%, (5.32+/-1.36)%, (0.70+/-0.30)%, (0.75+/-0.20)% vs. (10.99+/-0.35)%; 20
MUg/L NETs: (15.57+/-0.62)%, (13.28+/-0.65)%, (6.91+/-0.15)%, (5.86+/-0.17)% vs.
(16.85+/-0.49)%; 30 MUg/L NETs: (30.49+/-0.74)%, (29.41+/-1.41)%, (23.45+/
0.75)%, (21.72+/-1.52)% vs. (27.54+/-0.62)%, all P < 0.05]. CONCLUSIONS: NETs can
induce endothelial cell injury, and the injury degree was increased with the
concentration of NETs. Heparin can reduce endothelial cell injury induced by
NETs, which may be a potential mechanism for the protective effect of heparin on
sepsis.
PMID- 28420470
TI - [Explore objective clinical variables for detecting delirium in ICU patients: a
prospective case-control study].
AB - OBJECTIVE: The aim of this case-control study is to explore clinical objective
variables for diagnosing delirium of intensive care unit (ICU) patients. METHODS:
According to the method of prospective case-control study, critical adult
postoperative patients who were transferred to ICU of Peking University People's
Hospital from October 2015 to May 2016 and needed mechanical ventilation were
included. After evaluating the Richmond agitation sedation scale score (RASS),
the patients whose score were -2 or greater were sorted into two groups, delirium
and non-delirium, according to the confusion assessment method for the ICU (CAM
ICU). Then these patients were observed by domestic multifunctional detector for
electroencephalographic (EEG) variables such as brain lateralization, brain
introvert, brain activity, brain energy consumption, focus inward, focus outward,
cerebral inhibition, fatigue, sleep severity, sedation index, pain index, anxiety
index, fidgety index, stress index and the cerebral blood flow (CBF) index which
was named of perfusion index. Other variables including indexes of ICU blood gas
analysis, which was consisted of variables of blood gas analysis, routine blood
test and biochemistry, previous history and prognostic outcome was recorded.
Binary logistic regression was used for multivariate analysis. RESULTS: Forty
three postoperative patients, who needed intensive care, were included. Eighteen
were in delirium group and twenty-five in control group. Excluding the trauma,
variables like gender, age, temperature, heart rate, respiratory rate, mean
arterial pressure, acute physiology and chronic health evaluationII(APACHEII)
score, organ failure, dementia and emergency surgery didn't show any statistical
significance between two groups. The trauma in delirious patients increased
obviously compared with the control group (33.3% vs. 4.0%, P = 0.031). Except for
the brain activity [122.47 (88.62, 154.21) vs. 89.40 (86.27, 115.97), P = 0.034],
there were no statistical differences in any other EEG and CBF variables. In ICU
blood gas analysis, only pH value (7.43+/-0.42 vs. 7.47+/-0.31, P = 0.003),
chloride concentration [Cl- (mmol/L): 114.66+/-4.32 vs. 111.90+/-3.08, P =
0.019], magnesium concentration [Mg2+ (mmol/L): 0.60+/-0.10 vs. 0.54+/-0.06, P =
0.035] and blood osmolality [mmol/L: 290.10 (284.15, 306.35) vs. 282.70 (280.20,
286.75), P = 0.014] were statistically significant. Compared with control group,
the prognostic variables in delirium group such as duration of mechanical
ventilation [days: 125.0 (49.0, 293.0) vs. 149.5 (32.0, 251.3)], length of stay
in ICU [days: 216.5 (50.5, 360.8) vs. 190.0 (72.0, 330.5)] and mortality rate
(22.2% vs. 24.0%) didn't appear to be statistically significant either (all P >
0.05). It was shown by multivariate logistic regression analysis that pH [odds
ratio (OR) = 1.446, 95% confidence interval (95%CI) = 1.116-1.875, P = 0.005] and
Cl- (OR = 0.708, 95%CI = 0.531-0.945, P = 0.019) were potential risk factors of
delirium. CONCLUSIONS: The brain activity of HXD_I may contribute to the clinical
diagnose of delirium, but it still remained to be proved further. The pH and Cl-
are potential risk factors of delirium.
PMID- 28420471
TI - [Mixed venous-arterial carbon dioxide difference combined with passive leg
raising in guiding volume management for patients post off-pump coronary artery
bypass grafting].
AB - OBJECTIVE: To investigate whether mixed venous-arterial carbon dioxide difference
(Pv-aCO2) combined with passive leg raising (PLR) could better guide volume
management for patients post off-pump coronary artery bypass grafting (OPCABG).
METHODS: Eighty patients experienced OPCABG, and admitted to Tianjin Chest
Hospital from June 1st to October 1st in 2016 were enrolled. They were randomly
divided into two groups: observation group given Pv-aCO2 combined with PLR
directed therapy and control group given central venous pressure (CVP) directed
therapy, 40 cases in each group. The difference in body temperature (T), heart
rate (HR), mean arterial pressure (MAP), CVP, oxygenation index (PaO2/FiO2),
mixed venous oxygen saturation (SvO2), Pv-aCO2, blood lactate (Lac), fluid
intake, scores of the vasoactive agents at 6 hours post-operation, sequential
organ failure assessment (SOFA) of 24 hours, mechanical ventilation time, the
length of intensive care unit (ICU) stay, and hospitalization time were compared.
The correlation between Pv-aCO2 and cardiac index (CI), Pv-aCO2 and Lac were
analyzed by Spearman analysis in observation group. RESULTS: The T, HR, MAP, CVP,
PaO2/FiO2, SvO2 and Lac at 6 hours post-operation were higher than those at
admission in two groups, and Pv-aCO2 were significantly decreased. The SvO2 and
fluid intake in observation group were higher than those in control group [SvO2:
0.671+/-0.068 vs. 0.634+/-0.052, fluid intake (mL): 454+/-151 vs. 304+/-106, both
P < 0.05], Pv-aCO2, Lac and scores of the vasoactive agents were lower than those
in control group [Pv-aCO2 (mmHg, 1 mmHg = 0.133 kPa): 6.1+/-1.8 vs. 7.0+/-1.8,
Lac (mmol/L): 1.7+/-0.5 vs. 2.8+/-0.6, scores of the vasoactive agents: 3.18+/
1.01 vs. 4.48+/-1.50, all P < 0.05], mechanical ventilation time and the length
of ICU stay were less than those in the control group (hours: 16.52+/-6.41 vs.
21.96+/-9.00, 45.51+/-9.36 vs. 51.76+/-13.66, both P < 0.05). There was no
significant difference in SOFA, hospitalization time between the two groups.
There was negative correlation with Pv-aCO2 and CI (r = -0.752, P < 0.01), and no
correlation with Pv-aCO2 and Lac (r = -0.154, P = 0.171). CONCLUSIONS: Pv-aCO2
combined with PLR can better guide volume management in the patients post OPCABG,
reduce the usage of vasoactive agents and decrease the mechanical ventilation
time and the length of ICU stay.
PMID- 28420472
TI - [Analysis of the onset time of acute aortic dissection and the influence of
climate on acute aortic dissection occurrence in Urumqi city: a retrospective
study of a single center].
AB - OBJECTIVE: To observe the time characteristics of acute aortic dissection (AAD)
in Urumqi and its peripheral areas in Xinjiang Uygur autonomous region, and to
explore the effect of meteorological conditions on the onset of AAD. METHODS:
Retrospective analysis of the related data of the adult AAD patients diagnosed by
imaging examination, and admitted to the First Affiliated Hospital of Xinjiang
Medical University from March 2010 to July 2016 was performed. The onset time,
the contemporaneous meteorological data, including daily minimum, average, and
the highest temperature, daily average air pressure, daily average relative
humidity, daily precipitation, daily average wind speed, daily maximum wind
speed, and sunshine duration per day were collected. Analysis of concentrated
distribution trend of the AAD onset was done by circular distribution statistics.
Meteorological conditions were compared between "the AAD day" and "no AAD day".
The changes of air temperature 5 days before onset were observed. RESULTS: A
total of 379 patients were enrolled, with 307 male and 72 female. The ratio of
male to female was 4.19: 1, the average age was 52.27+/-12.18; and the underlying
diseases was hypertension (about 58.05%); the incidence sites were Urumqi and
Changji city. (1) The incidence of AAD in Urumqi and its peripheral areas had
clear concentrated trend, and the peak period of AAD corresponded to January 1st
to 2nd (homogeneity test r = 0.104, r 0.05 = 0.009, P < 0.05). (2) The minimum,
mean and maximal atmospheric temperatures on "the AAD day" were lower than "no
AAD day" [centigrade: 4.10 (-9.55, 14.60) vs. 7.75 (-6.70, 16.20), 14.10 (-1.50,
25.00) vs. 17.50 (0.60, 26.78), 8.50 (-6.22, 19.45) vs. 12.10 (-3.60, 20.90), all
P < 0.05], sunshine duration was significantly shorter than "no AAD day" [hours:
8.50 (4.60, 10.70) vs. 8.90 (5.50, 11.50), P < 0.01], and atmospheric pressure
were higher than "no AAD day" [kPa: 91.24 (90.66, 91.75) vs. 91.12 (90.62,
91.61), 19.11 (18.99, 19.22) vs. 19.09 (18.98, 19.19), both P < 0.05]; there were
no significant differences in the incidence of daytime temperature difference,
average relative humidity, precipitation, average wind speed, and maximum wind
speed between the two groups. (3) the peak period of AAD occurrence was December
(38 cases), which was followed by January (36 cases); and there were 26 cases of
each month in May, June, July, and September, which were lower than the rest of
months. It was shown by the temperature distribution that the minimum average
temperature was in January (-12.46 centigrade), followed by December (-9.03
centigrade); the maximum average temperature was in July [(24.59+/
3.21)centigrade], followed by August [(23.14+/-3.64)centigrade]. (4) The patients
was sorted according to the quartile of daily mean temperature, into < -5.2
centigrade, -5.2-10.7 centigrade, 10.7-20.4 centigrade, and > 20.4 centigrade
groups, and each group had 104, 99, 98, 78 cases of AAD, respectively. The number
of AAD in lowest temperature group was 1.33 times of the highest temperature
group. In the 45-59 and 60-74 years, the number of AAD in lowest temperature
group was higher than that in the highest temperature group (50 vs. 36, 26 vs.
13). In patients with hypertension, the number of AAD in lowest temperature group
was higher than that in the highest temperature group (60 vs. 44). (5) The
maximum air temperature, mean air temperature of the day from 5 days before to
the onset day of AAD, and the lowest temperature from 3 days before to the onset
day of AAD display slowly decrease trends, but there was no significant
difference in daily temperature. CONCLUSIONS: The incidence of AAD in Urumqi and
its peripheral areas was concentrated from January 1st to 2nd of each year. When
the temperature was lower than -5.2 centigrade, AAD were more likely to attack.
The 5 days changes of temperature and daily temperature before the attack were
relevant with onset of AAD. It was speculated that the weather conditions such as
air temperature may affect patient who has a past history of cardiovascular
disease to attack AAD.
PMID- 28420473
TI - [The study of serum complements and proinflammatory cytokines in sepsis rats].
AB - OBJECTIVE: To observe the changes of serum complements and proinflammatory
cytokines in rats with sepsis, and to explore the possible mechanism. METHODS:
120 healthy male Wistar rats were randomly divided into three groups: normal
control group (n = 15), sham operation group (n = 15) and sepsis group [cecum
ligation and puncture (CLP) operation, n = 90]. The sepsis rats were sacrificed
on 24, 48 and 72 hours after modeling. The level of serum complements (C5, C5a)
and cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1, IL-6),
high mobility group box 1 (HMGB1), macrophage migration inhibitory factor (MIF)
were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared
with normal control group and sham operation group, the levels of serum
complements C5, C5a and IL-1beta were significantly increased at 24 hours after
CLP in sepsis group [C5 (ng/L): 1.60+/-0.19 vs. 1.04+/-0.20, 1.09+/-0.09; C5a
(ng/L): 0.20+/-0.02 vs. 0.18+/-0.01, 0.18+/-0.02; IL-1beta (ng/L): 700.20+/
111.41 vs. 475.87+/-108.96, 592.29+/-121.57; all P < 0.05]; then the levels of
C5, C5a and IL-1beta declined, the level of serum C5 were also higher than normal
control group at 48 hours and 72 hours after CLP (ng/L: 1.17+/-0.24, 1.27+/-0.24
vs. 1.04+/-0.20, both P < 0.05). In sepsis group the level of serum TNF-alpha
(ng/L: 51.33+/-1.96, 51.06+/-1.64) was lower than that in normal control group
(59.53+/-3.06) and sham operation group (57.91+/-2.72) at 48 hours and 72 hours
(all P < 0.05). There was a time dependent rise of serum HMGB1 in sepsis group,
which level was much higher than that in normal control group and sham operation
group at 72 hours after CLP (ng/L: 472.21+/-20.94 vs. 406.00+/-43.16, 404.41+/
35.39, both P < 0.05). There were no significant differences of MIF, and IL-6
level between groups at each time points. CONCLUSIONS: Complement system led to
uncontrolled inflammatory response and immune dysfunction through the release of
proinflammatory cytokines and inflammatory mediators, which maybe one of the
important mechanism of the pathology of sepsis.
PMID- 28420474
TI - [Value of APACHEIIfor predicting the nursing workload in EICU].
AB - OBJECTIVE: To investigate the predictive value of acute physiology and chronic
health evaluationII(APACHEII) for nursing workload in emergency intensive care
unit (EICU). METHODS: A retrospective cohort study was conducted. Critical
patients except for trauma admitted to EICU of West China Hospital of Sichuan
University from June 2012 to July 2016 were enrolled. APACHEII score and
therapeutic intervention scoring system (TISS-28) score were calculated in each
case. The relationship between APACHEIIscore and TISS-28 score was analyzed by
correlation analysis and curve estimation. RESULTS: A total of 1 148 patients
were enrolled, including 689 male (60.0%), and age of (56+/-19) years old,
APACHEII score was 19 (13, 25), and TISS score was 19 (13, 25). The Spearman
correlation coefficient between APACHEII score and TISS-28 score was 0.849 (P <
0.001), and that among the linear model quadratic model, composite model, growth
model, logarithm model, cubic model and exponential model R 2 were 0.669, 0.710,
0.792, 0.764, 0.765, 0.765, respectively (all P < 0.01), and the most suitable
description for relationship between APACHEIIscore and TISS-28 score curve was
cubic model. The nursing workload was significantly increased when APACHEII score
>=30, and it was decreased when APACHEII score < 30. CONCLUSIONS: APACHEIIwas a
useful score for predicting the nursing workload in EICU.
PMID- 28420475
TI - [Design and application of emergency rescue bag in pediatrics].
PMID- 28420476
TI - [Mechanism of resolvins in reducing the inflammation reaction in inflammatory
diseases].
AB - OBJECTIVE: Inflammation is an important mechanism for the host to resist external
infection and injury. Under normal conditions, adaptive inflammatory response not
only is conducive to the repair of damaged cells and tissues, but plays an
important role to promote the internal environment to restored homeostasis.
However, when the immune function is damaged, the unresolved and uncontrolled
inflammation will cause non-specific tissue damage, which is linked to a variety
of inflammatory diseases. In the acute inflammation, resolvins, a group of
endogenous small molecular lipid mediators which are biosynthesized by
polyunsaturated fatty acids, possess anti-inflammatory and pro-resolving actions,
which are benefit for the repair of damaged tissue. Therefore, it is helpful to
deeply explore the mechanisms of resolvins in inflammation-resolution phases of
acute lung injury (ALI) and sepsis, which are favor of understanding the complex
processes and provide new treatment for the inflammatory diseases thereby
reducing the mortality in the intensive care unit (ICU).
PMID- 28420477
TI - [Metabolism of high density lipoprotein and the research progress of its effects
on sepsis].
AB - OBJECTIVE: Sepsis is a high-risk factor for the death of critical patients. High
density lipoprotein (HDL) are the major protective serum proteins, and the serum
levels of HDL are closely related to the severity of sepsis. The anti
inflammatory and anti-oxidation properties of HDL, may be able to play an
important role in the innate immune response. Thereby it may reduce the damage of
septic shock and multiple organ dysfunction syndrome (MODS) in animals or human
beings, and improve the prognosis. In order to unveil the metabolism of HDL in
septic patients and its effects on both progression and prognosis of sepsis, this
review not only focuses on the composition and structure of HDL, but also
analyzes its pivotal role in inflammatory immune response and anti-oxidation.
PMID- 28420478
TI - [Research progress on metabolism of monocytes and macrophages in sepsis].
AB - OBJECTIVE: During sepsis, circulating leukocytes are in a hyper inflammatory
state, and with the progress of the inflammation, immune cells may become
tolerated. Glycolysis and pentose phosphate pathway are up-regulated but
oxidative phosphorylation is suppressed in hyper inflammatory cells, whereas
during immune tolerance, glycolysis is often down-regulated. In this review, we
will summarize the changes of cellular metabolic pathways in monocytes and
macrophages during sepsis. We also review how the metabolism of glucose, amino
acids, and fatty acids affect the function of monocytes and macrophages in
sepsis. Current literature indicated that metabolism plays a significant role in
regulating the functions of immune cells in sepsis, which might be a potential
therapy for sepsis and deserved further research.
PMID- 28420479
TI - Andrographolide disrupts meiotic maturation by blocking cytoskeletal
reorganisation and decreases the fertilisation potential of mouse oocytes.
AB - Andrographolide (AG) is a diterpenoid lactone isolated from the stem and leaves
of Andrographis paniculata Nees that is used for the effective treatment of
infectious diseases in Asian countries. Previous studies have reported adverse
effects of AG on female fertility in rodents; however, the underlying mechanisms
are unknown. The aim of the present study was to investigate the effects of AG on
the IVM of mouse oocytes and their fertilisation potential. Immature oocytes
incubated for 6, 14 or 24h in medium containing 5, 10 or 20MUM AG showed time-
and dose-dependent decreases in maturation rates compared with the control group.
Immunostaining revealed that AG exposure disrupted spindle organisation and
migration, as well as actin cap formation and cytokinesis. Furthermore, most
oocytes exposed to 20MUM AG underwent apoptosis, and the few oocytes exposed to 5
or 10MUM AG that reached MII exhibited lower fertilisation rates after
intracytoplasmic sperm injection. The findings of the present study suggest that
AG may disrupt mouse oocyte meiotic maturation by blocking cytoskeletal
reorganisation, and may thus have an adverse effect on female fertility.
PMID- 28420480
TI - Comparative analysis of granulosa cell gene expression in association with oocyte
competence in FSH-stimulated Holstein cows.
AB - Ovarian stimulation with exogenous FSH followed by FSH withdrawal or 'coasting'
is an effective means of increasing the number of oocytes obtainable for the in
vitro production of cattle embryos. However, the quality of the oocytes thus
obtained varies considerably from one cow to the next. The aim of the present
study was to gain a better understanding of the follicular conditions associated
with low oocyte developmental competence. Granulosa cells from 94 Holstein cows
in a commercial embryo production facility were collected following ovarian
stimulation and coasting. Microarray analysis showed 120 genes expressed with a
differential of at least 1.5 when comparing donors of mostly competent with
donors of mostly incompetent oocytes. Using ingenuity pathway analysis, we
revealed the main biological functions and potential upstream regulators that
distinguish donors of mostly incompetent oocytes. These are involved in cell
proliferation, apoptosis, lipid metabolism, retinol availability and insulin
signalling. In summary, we demonstrated that differences in follicle maturity at
collection could explain differences in oocyte competence associated with
individual animals. We also revealed deficiencies in lipid metabolism and retinol
signalling in granulosa cells from donors of mostly incompetent oocytes.
PMID- 28420481
TI - Safety and Feasibility of Subcutaneous Purse-String Suture of the Femoral Vein
After Electrophysiological Procedures on Uninterrupted Oral Anticoagulation.
AB - The aim of this study was to compare safety and feasibility of a subcutaneous
purse-string suture (PSS) with manual compression (MC) to gain hemostasis in
patients after multiple femoral venous punctures undergoing electrophysiological
procedures on uninterrupted oral anticoagulation (OAK). A total of 784 patients
who underwent catheter ablation for atrial fibrillation (n = 564) or (a)typical
atrial flutter (n = 220) were assessed. Four hundred sixty-two patients received
PSS (58.9%) and 322 patients (41.1%) received MC to gain hemostasis. All patients
were on uninterrupted full-dose OAK. During the procedure, weight-adapted heparin
was applied. Venous sheath diameter were 8Fr (n = 2)/11.5Fr (n = 1) for left
atrial or 8Fr (n = 1)/6Fr (n = 2) for right atrial procedures. No protamine was
administered at the end of the procedure. After PSS, patients' had 6 hours of bed
rest compared with 10 hours after MC (sheath removal after 4 hours followed by a
bandage for 6 hours). PSS was removed the following day. All patients underwent
duplex sonography of the access site the following day. Using the PSS, hemostasis
was achieved in 453 of 462 patients (98%). MC leads to hemostasis in all 322
patients. No difference was found between the 2 approaches regarding hematomas
(<5 cm or >5 cm), arterio-venous fistulas, or pseudoaneurysms. No major
complication such as ipsilateral leg ischemia, the need of vascular surgery, or
deep vein thrombosis occurred. In conclusion, PSS is a safe and effective way to
gain immediate hemostasis after multiple punctures of the femoral vein in
patients undergoing catheter ablation on OAK. PSS avoids MC and leads to shorter
patient immobilization.
PMID- 28420482
TI - Detection of driver drowsiness using wearable devices: A feasibility study of the
proximity sensor.
AB - BACKGROUND: Drowsiness is one of the major factors that cause crashes in the
transportation industry. Drowsiness detection systems can alert drowsy operators
and potentially reduce the risk of crashes. In this study, a Google-Glass-based
drowsiness detection system was developed and validated. METHODS: The proximity
sensor of Google Glass was used to monitor eye blink frequency. A simulated
driving study was carried out to validate the system. Driving performance and eye
blinks were compared between the two states of alertness and drowsiness while
driving. RESULTS: Drowsy drivers increased frequency of eye blinks, produced
longer braking response time and increased lane deviation, compared to when they
were alert. A threshold algorithm for proximity sensor can reliably detect eye
blinks and proved the feasibility of using Google Glass to detect operator
drowsiness. APPLICATIONS: This technology provides a new platform to detect
operator drowsiness and has the potential to reduce drowsiness-related crashes in
driving and aviation.
PMID- 28420483
TI - An evaluation of wearable sensors and their placements for analyzing construction
worker's trunk posture in laboratory conditions.
AB - This study investigates the effect of sensor placement on the analysis of trunk
posture for construction activities using two off-the-shelf systems. Experiments
were performed using a single-parameter monitoring wearable sensor (SPMWS), the
ActiGraph GT9X Link, which was worn at six locations on the body, and a multi
parameter monitoring wearable sensor (MPMWS), the Zephyr BioHarnessTM3, which was
worn at two body positions. One healthy male was recruited and conducted 10
experiment sessions to repeat measurements of trunk posture within our study.
Measurements of upper-body thoracic bending posture during the lifting and
lowering of raised deck materials in a laboratory setting were compared against
video-captured observations of posture. The measurements from the two sensors
were found to be in agreement during slow-motion symmetric bending activities
with a target bending of <=45 degrees . However, for asymmetric bending tasks,
when the SPMWS was placed on the chest, its readings were substantially different
from those of the MPMWS worn on the chest or under the armpit.
PMID- 28420484
TI - Prenatal diagnosis of Ectrodactyly-Ectodermal dysplasia-Cleft (EEC) syndrome in a
Chinese woman with a TP63 mutation.
PMID- 28420486
TI - Vitamins C and D.
PMID- 28420485
TI - Subcutaneous dermatofibrosarcoma protuberans, a rare subtype with predilection
for the head: A retrospective series of 18 cases.
AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) typically affects the dermis
and subcutaneous tissue. The subcutaneous variant is rare. OBJECTIVE: We sought
to characterize the subcutaneous DFSP (SC-DFSP) variant and compare it with
cutaneous DFSP (C-DFSP). METHODS: This work was a retrospective study of DFSP
treated in our institution. RESULTS: Of 124 cases of DFSP, 18 were SC-DFSP
(14.5%). Except for the deep location, the pathologic and genetic features were
indistinguishable from the C-DFSP variant. Histologically, of 18 SC-DFSP cases,
13 were classic DFSP, 3 fibrosarcomatous DFSP (FS-DFSP), 1 Bednar tumor, and 1
giant-cell fibroblastoma. All tumors expressed CD34 and the COL1A1-PDGFB fusion
transcripts. In our series, higher proportions of SC-DFSP tumors (61%) than C
DFSP tumors (8.5%) were located on the head (P < .001). Of the 20 DFSP tumors on
the head (16.1%), 11 were SC-DFSP and 9 were C-DFSP. In addition, half the SC
DFSP tumors affected muscle or periosteum, compared with a quarter of the C-DFSP
tumors (P = .009). SC-DFSP needed a higher number of Mohs stages than did C-DFSP
(P = .009). Median follow-up time was 63 months, and 2 FS-DFSP tumors recurred (1
SC-DFSP, 1 C-DFSP). LIMITATIONS: Limitations include the retrospective aspect of
the study. CONCLUSIONS: Most DFSP tumors involving the head were subcutaneous and
required more complex surgery. Dermatologists should be aware of this atypical
presentation, especially in lesions involving the head.
PMID- 28420487
TI - Personal protective equipment solution for UK military medical personnel working
in an Ebola virus disease treatment unit in Sierra Leone.
AB - The combination of personal protective equipment (PPE) together with donning and
doffing protocols was designed to protect British and Canadian military medical
personnel in the Kerry Town Ebola Treatment Unit (ETU) in Sierra Leone. The PPE
solution was selected to protect medical staff from infectious risks, notably
Ebola virus, and chemical (hypochlorite) exposure. PPE maximized dexterity,
enabled personnel to work in hot temperatures for periods of up to 2h, protected
mucosal membranes when doffing outer layers, and minimized potential
contamination of the doffing area with infectious material by reducing the
requirement to spray PPE with hypochlorite. The ETU was equipped to allow medical
personnel to provide a higher level of care than witnessed in many existing ETUs.
This assured personnel working as part of the international response that they
would receive as close to Western treatment standards as possible if they were to
contract Ebola virus disease (EVD). PPE also enabled clinical interventions that
are not seen routinely in West African EVD treatment regimens, whilst providing a
robust protective barrier. Competency in using PPE was developed during a nine
day pre-deployment training programme. This allowed over 60 clinical personnel
per deployment to practice skills in PPE in a simulated ETU and in classrooms.
Overall, the training provided: (i) an evidence base underpinning the PPE
solution chosen; (ii) skills in donning and doffing of PPE; (iii) personnel
confidence in the selected PPE; and (iv) quantifiable testing of each
individual's capability to don PPE, perform tasks and doff PPE safely.
PMID- 28420488
TI - Mandibular step osteotomy using CAD/CAM-derived surgical splint: case report.
AB - Mandibular step osteotomy is a useful technique for large mandibular setbacks. We
report a case of a patient who had a mandibular step osteotomy using a CAD/CAM
derived wafer for mandibular setback with reduction of the arch.
PMID- 28420489
TI - Mast cells emerge as mediators of atherosclerosis: Special emphasis on IL-37
inhibition.
AB - In atherosclerosis lipoproteins stimulate the innate immune response, leading to
the release of inflammatory cytokines and chemokines. Hypercholesterolemia may
activate the synthesis and release of inflammatory cytokines such as IL-1, which
induces TNF release in mast cells (MCs). IL-1 and IL-1 family members orchestrate
a broadening list of inflammatory diseases, including atherosclerosis. MCs are
implicated in the pathophysiology of several diseases including allergy and
inflammation. Activated MCs, located perivascularly, contribute to inflammation
in atherosclerosis by producing inflammatory cytokines. MC IL-1-activation leads
to the immediate release of inflammatory chemical mediators and TNF, and late
inflammatory compounds such as cytokines. MCs can be activated by exogenous
cytokines, antigens, microbial products (LPS) and neurotransmitters and generate
IL-1 beta, TNF and several other inflammatory cytokines/chemokines along with
PGD2, leukotrienes, histamine and proteases. MCs activated with IL-1 induce
selective release of IL-6 without degranulation. TNF emerges as one of the most
potent inflammatory cytokines involved in the response due to LDL. Cytokines,
such as IL-1, IL-6, IL-33 and TNF, are generated in the inflammatory sites by
both macrophages and MCs, mediating atherosclerosis. IL-37 (IL-1 family member 7)
binds IL-18Ra chain and acts by an intracellular mechanism down-regulating the
expression of pro-inflammatory signals cJun, MAP kinase p38a, STAT transcription
factors and p53. Blocking IL-1 with IL-37 alleviates the symptoms in patients
with inflammatory diseases including arteriosclerosis. The impact of IL-37 on
inflammatory cytokines mediating atherosclerosis is beneficial and protective.
However, more studies are needed to better define this mechanism and the safety
and tolerability of IL-37.
PMID- 28420490
TI - Are herbarium mosses reliable indicators of historical nitrogen deposition?
AB - Mosses collected decades ago and stored in herbaria are often used to assess
historical nitrogen deposition. This method is effectively based on the
assumption that tissue N concentration remains constant during storage. The
present study raises serious doubt about the generality of that assumption. We
measured tissue N and C concentrations as well as delta15N, delta13C, Pb and Mg
in herbarium and present day samples of seven bryophyte species from six sites
across Denmark. While an increase in nitrogen deposition during the last century
is well-documented for the study site, we surprisingly found foliar N
concentration to be higher in historical samples than in modern samples. Based on
delta15N values and Pb concentration, we find nitrogen contamination of herbarium
specimens during storage to be the most likely cause, possibly in combination
with dilution though growth and/or decomposition during storage. We suggest ways
to assess contamination and recommend caution to be taken when using herbarium
specimens to assess historical pollution if exposure during storage cannot be
ruled out.
PMID- 28420491
TI - Telemedicine for patients with rheumatic diseases: Systematic review and proposal
for research agenda.
AB - OBJECTIVE: To systematically review the scientific literature regarding tele
rheumatology and draw conclusions about feasibility, effectiveness, and patient
satisfaction. METHODS: PubMed, Scopus, and Cochrane database searches were
performed (April 2016) using relevant MeSH and keyword terms for telemedicine and
rheumatic diseases. Articles were selected if reporting outcomes for feasibility,
effectiveness, and patient satisfaction and methodologically appraised using the
Cochrane Collaboration's tool for assessing risk of bias and a modified version
of CONSORT 2010 Statement. RESULTS: A total of 177 articles were screened, 23
were selected for the present review but only 9 were RCTs. Five studies reported
on feasibility, 14 effectiveness, and 9 satisfaction rates for different tele
rheumatology interventions grouped in synchronous (remotely delivered
consultation) and asynchronous (remote disease activity assessment; tele
monitoring of treatment strategies or rehabilitation; and remotely delivered self
management programs). Seven studies (30.4%) were on rheumatoid arthritis, 2
(8.7%) were on systemic sclerosis (1 including also rheumatoid arthritis
patients), 5 (21.7%) on fibromyalgia, 2 (8.7%) on osteoarthritis, 3 (13.0%) on
juvenile idiopathic arthritis and 4 (17.4%) on mixed disease cohorts.
Interventions and outcomes heterogeneity prevented meta-analysis of results.
Overall, feasibility and patient satisfaction rates were high or very high across
intervention types. Effectiveness was equal or higher than standard face-to-face
approach in controlled trials which, however, were affected by small sample size
and lack of blinding participants according to appraisal tools. CONCLUSION:
Telemedicine may provide a well-accepted way to remotely deliver consultation,
treatment and monitoring disease activity in rheumatology. Higher quality RCTs
demonstrating effectiveness of different tele-rheumatology interventions are
needed.
PMID- 28420492
TI - Commentary on: Research priorities for a multicenter child abuse pediatrics
network - CAPNET by Lindberg D et al., 2017: Need for internationally agreed
definitions of Child Maltreatment for research purposes.
PMID- 28420493
TI - Etiology of Human Genetic Disease on the Fly.
AB - The model organism Drosophila melanogaster has been at the forefront of genetic
studies since before the discovery of DNA. Although human disease modeling in
flies may still be rather novel, recent advances in genetic tool design and
genome sequencing now confer huge advantages in the fly system when modeling
human disease. In this review, we focus on new genomic tools for human gene
variant analysis; new uses for the Drosophila Genetic Reference Panel (DGRP) in
detection of background alleles that influence a phenotype; and several examples
of how multigenic conditions, both complex disorders and duplication and/or
deletion syndromes, can be effectively studied in the fly model system. Fruit
flies are a far cry from the quaint genetic model of the past, but rather,
continue to evolve as a powerful system for the study of human genetic disease.
PMID- 28420494
TI - Molecular regulation and role of angiogenesis in reproduction.
AB - Angiogenesis is an essential process for proper functioning of the female
reproductive system and for successful pregnancy realization. The multitude of
factors required for physiological angiogenesis and the complexity of regulation
of their temporal-spatial activities contribute to aberrations in human
fertilization and pregnancy outcomes. In this study, we reviewed the current
knowledge of the temporal expression patterns, functions, and regulatory
mechanisms of angiogenic factors during foliculogenesis, early
implantation/placentation and embryo development, as well as recurrent
spontaneous abortions. Angiogenic factors including vascular endothelial growth
factors and angiopoietins have documented roles in the development of primordial
follicles into mature antral follicles. They also participate in decidualization,
which is accompanied by the creation of an extensive network of vessels in the
stromal bed that support the growth of the embryo and the placenta, and maintain
early pregnancy. During placentation angiogenic and angiomodulatory cytokines, T
and B lymphocytes and macrophages affect angiogenesis in a context-dependent
manner. Defects in angiogenesis at the maternal-fetal interface contribute to
miscarriage in humans. The establishment of more polymorphisms in the genes
involved in angiogenesis/vasculogenesis, and their pathological phenotype and
expression could give opportunities for prediction, creating a therapeutic
strategy, and treatment of diseases related to female reproductive health and
problematic conception.
PMID- 28420495
TI - Fetal programming of the metabolic syndrome.
AB - Prenatal development is currently recognized as a critical period in the etiology
of human diseases. This is particularly so when an unfavorable environment
interacts with a genetic predisposition. The fetal programming concept suggests
that maternal nutritional imbalance and metabolic disturbances may have a
persistent and intergenerational effect on the health of offspring and on the
risk of diseases such as obesity, diabetes, and cardiovascular diseases.
PMID- 28420496
TI - The value of hysteroscopic management of cesarean scar pregnancy: a report of 44
cases.
AB - OBJECTIVE: With the incidence of cesarean scar pregnancy (CSP) rising, the
reports of serious adverse outcomes of it have increased gradually. The
management of CSP remains an inadequately explored clinical field, and there is
no consensus on it presently. The present study was performed to investigate the
efficacy and safety of operative hysteroscopy in the diagnosis and treatment of
CSP. MATERIALS AND METHODS: Forty-four patients with CSP underwent operative
hysteroscopy for removal of scar ectopic pregnancy in our institution. Among
them, hysteroscopy was combined with laparoscopy in two patients, three cases
with massive hemorrhage were pretreated with bilateral uterine artery
embolization before hysteroscopic surgery, and four patients were pretreated with
mifepristone (200 mg for 3 days) and methotrexate (25 mg for 2 days). Clinical
data, serum beta-human chorionic gonadotropin, myometrial thickness, residual
conceptus, cesarean scar defect, operation time, blood loss, and hospital stay
were recorded. RESULTS: All of the ectopic gestations were removed entirely by
operative hysteroscopy. Mean operation time was 34.8+/-16.5 minutes (range 20-120
minutes), and mean blood loss was 35.3+/-24.4 mL (range 5-100 mL). The mean
hospital stay was 5.0+/-3.01 days (range 1-19 days). Cesarean scar defect could
be diagnosed in 70% (31/44) of patients, while in 20/32 cases (63%), a conceptus
remained after uterine curettage only was performed. CONCLUSION: Operative
hysteroscopy might be recommended as a first-line treatment modality for patients
with a cesarean scar ectopic pregnancy, especially when myometrium thickness
between bladder and gestational sac is more than 3 mm.
PMID- 28420497
TI - Radical trachelectomy for early stage cervical cancer: A case series and
literature review.
AB - OBJECTIVE: Radical trachelectomy (RT) is an alternative treatment for preserving
fertility in patients with cervical cancer. Because women with operable cervical
cancer opting for fertility preservation are scarce, few cases have been reported
in Taiwan. Here we report our cases series. MATERIALS AND METHODS: We
retrospectively evaluated seven patients who underwent vaginal RT and three
patients who underwent abdominal RT in a single medical institute for a median
follow-up period of 5 years. RESULTS: The oncological outcome was highly
satisfactory. All patients survived and are currently disease-free, except for
two who had recurrence and received additional concurrent chemoradiation therapy.
Other complications included urinary tract infection, cervical stenosis, and
unilateral hydronephrosis. All complications were manageable with little long
term effects. However, no pregnancy was observed during the 5-year follow-up
period. CONCLUSION: RT is considered a complicated surgical procedure among
gynecological operations. Here we review the literature and describe several
factors associated with higher pregnancy rates.
PMID- 28420498
TI - Intraoperative aortic balloon occlusion in patients with placenta previa and/or
placenta accreta: a retrospective study.
AB - OBJECTIVE: To introduce the primary experience of using aortic balloon catheters
during cesarean section for placenta previa and/or placenta accreta. MATERIALS
AND METHODS: From January 2013 to May 2015, 43 patients who were preoperatively
diagnosed with major placenta previa and/or placenta accreta and who underwent
prophylactic aortic catheterization before caesarean section (CS) were included
in the study. We analyzed the clinical data of the study population. Surgery- and
catheterization-related complications were also reported. RESULTS: Major placenta
previa or placenta accreta was surgically confirmed in 42 patients, 28 of whom
had both conditions. The mean patient age was 32.3 +/- 5.5 years, whereas the
median gestational age at delivery was 260 (range, 153-280) days. Twenty-nine
(67.4%) patients had previously undergone CS, and 13 (30%) patients had undergone
emergency surgery for antenatal hemorrhage. The median estimated blood loss
during surgery was 500 (range, 100-3,000) mL, and the median duration of
occlusion was 20 (range, 5-32) minutes. Hysterectomy was performed in five
(11.6%) patients and uterine artery embolization in two (4.6%) patients. Two
patients with placenta percreta experienced surgery-related complications, and
two patients required hospital readmission. No major catheterization-related
complications were observed. Forty-two live births were recorded, and the Apgar
score of the infants at 5 minutes was > 7. CONCLUSION: Intraoperative aortic
balloon occlusion is a relatively safe method for treating placenta previa and/or
placenta accreta during scheduled and emergency CS and might be helpful to
prevent hysterectomy and embolization in women wishing to preserve fertility.
PMID- 28420499
TI - The associations between parity, other reproductive factors, and osteoarthritis
in women aged over 50 years; data from the Korean National Health and Nutrition
Examination Survey V (2010-2012).
AB - OBJECTIVE: To evaluate the relationships between sociodemographic factors,
reproductive history, and subsequent risk of osteoarthritis (OA) or pain of the
hip, knee, and back in Korean women. MATERIALS AND METHODS: This study included
data of 5101 women aged over 50 years, taken from the Korean National Health and
Nutritional Examination Survey V from 2010 to 2012. Women were stratified
according to parity, as well as delivery mode. Multivariate logistic regression
analysis was conducted to evaluate relationships between radiographic OA or
symptomatically possible OA (back, knee, or hip), and historical factors.
RESULTS: Vaginal delivery was associated with an increased risk of symptomatic
back OA [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.062, 2.881] but was
not associated with symptomatic knee and hip OA in adjusted analysis.
Radiographically, vaginal delivery was not associated with risks of back and knee
OA, but was negatively associated with hip OA (OR 0.184, 95% CI 0.039, 0.863),
compared to cesarean delivery. High parity (over 5) was associated with
radiographic knee OA (OR 1.328, 95% CI 1.006, 1.754) in adjusted analysis. High
parity (over 3) was associated with symptomatic back OA. CONCLUSION: Parity was
associated with higher risk of radiographic knee OA. Vaginal delivery was
positively associated with symptomatic back OA, but negatively associated with
radiographic knee OA. Further study is required to evaluate the mechanism between
delivery mode and subsequent OA.
PMID- 28420500
TI - Does different BMI influence oocyte and embryo quality by inducing fatty acid in
follicular fluid?
AB - OBJECTIVE: We aimed to assess the effects of obesity-related follicular fluid
(FF) fatty acids (FAs) on the number and quality of oocytes, good embryo quality
rate, and pregnancy rate. MATERIALS AND METHODS: This prospective cohort study
was conducted on 105 infertile women under the age of 38, who underwent
intracytoplasmic sperm injection (ICSI) from March 2015 to October 2015. They
were grouped into three body mass index (BMI) categories. The fatty acids
composition of the FF was analyzed by GC-MS head space method. We studied the FAs
correlation with BMI and ICSI outcomes. RESULTS: The distribution of fatty acids
did not differ significantly in each BMI group, with the exception for stearic
that was marginally significant (p=0.05). The mean number of mature oocytes did
not differ significantly between the BMI groups, the percent of Metaphase II
(MII) oocytes was inversely associated with the BMI (rs=-0.21, p=0.03). Kruskal
Wallis test showed that the distribution of good quality embryos' percentages
were different in at least two categories of studied BMI groups (p=0.009,
p=0.02). The mean concentration of palmitic acid was higher in nonpregnant
patients for all of the studied BMI classes (p=0.02, p=0.03, p=0.05), however,
stearic (p<0.001) and linolenic acids (p=0.01) were higher in nonpregnant normal
weight patients. CONCLUSION: Differences in BMI are not associated with the fatty
acid composition of the FF. The FF fatty acid possibly affects the outcome of
ICSI through the achievement of clinical pregnancy. Therefore, it is essential to
provide patients with nutritional counseling before they use assisted
reproductive techniques.
PMID- 28420501
TI - Bioinformatics analysis of gene expression profiles in B cells of postmenopausal
osteoporosis patients.
AB - OBJECTIVE: The aim of this study was to gain a better understanding of the
molecular mechanisms and identify more critical genes associated with the
pathogenesis of postmenopausal osteoporosis (PMOP). MATERIALS AND METHODS:
Microarray data of GSE13850 were download from the Gene Expression Omnibus
database. Differentially expressed genes (DEGs) were identified either in B cells
from postmenopausal female nonsmokers with high bone mineral density (BMD)
compared with those with low BMD (defined as DEG1 group) or in B cells from
postmenopausal female smokers with high BMD compared with postmenopausal female
nonsmokers with high BMD (defined as DEG2 group). Gene ontology and immune
related functional enrichment analysis of DEGs were performed. Additionally, the
protein-protein interaction network of all DEGs was constructed and subnetworks
of the hub genes were extracted. RESULTS: A total of 51 DEGs were identified in
the DEG1 group, including 30 up- and 21 downregulated genes. Besides, 86 DEGs
were identified in the DEG2 group, of which 46 were upregulated and 40 were
downregulated. Immune enrichment analysis showed DEGs were mainly enriched in
functions of CD molecules and chemokines and receptor, and the upregulated gene
interleukin 4 receptor (IL-4R) was significantly enriched. Moreover, guanine
nucleotide-binding protein G (GNAI2), filamin A alpha (FLNA), and transforming
growth factor-beta1 (TGFB1) were hub proteins in the protein-protein interaction
network. CONCLUSION: IL-4R, GNAI2, FLNA, and TGFB1 may be potential target genes
associated with the pathogenesis of PMOP. In particular, FLNA, and TGFB1 may be
affected by smoking, a risk factor of PMOP.
PMID- 28420502
TI - The impact of situation-background-assessment-recommendation (SBAR) on safety
attitudes in the obstetrics department.
AB - OBJECTIVE: Previous studies evaluating the situation-background-assessment
recommendation (SBAR) have been shown to increase effective nurse-physician
communication and collaboration. The purpose of this study is to evaluate the
impact of the SBAR technique on safety attitudes in the obstetrics department.
MATERIALS AND METHODS: This study implemented the SBAR Collaborative
Communication Education course and was conducted in a medical center from
February 2012 to March 2015, which included an educational session on fetal heart
rate monitoring, a case-based discussion, and a video demonstration on
traditional and SBAR communication. The nurses in the obstetrics department were
requested to report their clinical findings and recommendations using a novel
SBAR list when abnormal fetal heart beat tracings occurred. All obstetric nurses
were requested to complete the Chinese-version of the Safety Attitudes
Questionnaire before and after the SBAR educational course. The primary outcome
was to evaluate the effect of the SBAR technique on the safety attitudes of the
obstetrics department. The secondary outcome was to evaluate the effect of the
SBAR technique on the 5-minute Apgar score for neonates. RESULTS: Most values,
including teamwork climate, safety climate, job satisfaction, and working
conditions, significantly improved at both postintervention surveys compared with
the preintervention survey. There were no significant differences in the number
of the neonates with less than seven 5-minute Apgar scores between the pre- and
postintervention periods. CONCLUSION: The SBAR technique, which uses a novel
structured handover list, is a feasible tool for nurse-obstetrician
communication, and it may improve most dimensions of safety attitudes in the
obstetrics department.
PMID- 28420503
TI - Age is a major prognosticator in extremely low oocyte retrieval cycles.
AB - OBJECTIVE: Clinical prognosis appears to be varied in females with poor ovarian
response (POR), and poor responders defined by the Bologna criteria might not be
sufficiently homogeneous. The aim of this study was to determine the major
predictor of reproductive outcomes in extremely low oocyte retrieval cycles.
MATERIALS AND METHODS: A cohort of fresh in vitro fertilization/intracytoplasmic
sperm injection cycles (n = 858) was analyzed from January 2001 to September
2014. Females from whom zero, one, two, or three oocytes were retrieved following
ovarian stimulation were examined. Univariate analyses were performed to
determine the association of pregnancy rate with potential confounding variables.
Multiple logistic regression analysis was subsequently performed to identify
factors that affected the occurrence of pregnancy. RESULTS: The clinical
pregnancy rate was higher in women aged < 40 years, long protocol, and high
embryo score in univariate analysis. After adjusting for confounding factors in
multivariate analysis, the maternal age [odds ratio (OR) = 0.91], primary or
secondary infertility (OR = 1.99), number of matured oocytes retrieved (OR =
0.64), and score of embryos transferred (OR = 1.39) were significantly associated
with the clinical pregnancy rate per cycle and per transfer. In the age subgroup
analysis, POR females aged < 35 years significantly demonstrated the highest
number of matured oocytes, embryo scores, and clinical pregnancy rates compared
with POR females aged 35-40 years and >= 40 years. CONCLUSION: This study
highlights the predictive value of maternal age and embryo quality on the
probability of pregnancy in females with extremely low oocyte retrieval cycles.
Young females with few eggs collected can still achieve acceptable pregnancy
probability as long as they have good-quality embryos. Future randomized control
trials for POR using the Bologna criteria should first stratify patients into
different age groups.
PMID- 28420504
TI - The clinical profile of young and adolescent women with laparoscopically
diagnosed endometriosis in a Singapore tertiary hospital.
AB - OBJECTIVE: Endometriosis has been increasingly recognized as the cause of severe
dysmenorrhea among younger women including adolescents, often with significant
delay from time of presentation to diagnosis. Data on the South East Asian women
is scarce. This study aims to describe the disease pattern in a group of young
Asian women with histological diagnosis of endometriosis in our center. MATERIALS
AND METHODS: A total of 709 laparoscopic operations were performed for
endometriosis in our center between 2000 and 2007. Women aged 25 years old and
below were included in this study. Details regarding clinical presentation and
severity of disease were retrospectively reviewed and described. RESULTS: A total
of 45 women were included in this study, aged between 14 years and 25 years.
Thirty seven patients (82.3%) were aged between 21 years and 25 years. Racial
distribution was as follows: 57.8% Chinese, 26.7% Malay, and 15.6% Indian.
Dysmenorrhea was the commonest symptom (84.4%); 44.4% of which were described as
mild. Eleven patients (24.4%) presented with severe symptoms resulting in absence
from school or work. Severity of endometriosis during laparoscopy was staged
using the rAFS staging system, and was 11.1%, 17.8%, 28.9%, and 42.2% for disease
Stage I, Stage II, Stage III, and Stage IV, respectively. CONCLUSION:
Endometriosis can cause severe disease even in adolescents and young females.
Increased awareness among patients and healthcare providers would raise a higher
index of suspicion for endometriosis in these women, with consequent early
treatment which may result in better functional and fertility outcomes.
PMID- 28420505
TI - Risk factors and management of vaginal mesh erosion after pelvic organ prolapse
surgery.
AB - OBJECTIVE: Mesh erosion is a serious and not uncommon complication in women
undergoing vaginal mesh repair. We hypothesized that mesh erosion is associated
with the patient's comorbidities, surgical procedures, and mesh material. The
aims of this study were to identify the risk factors and optimal management for
mesh erosion. MATERIALS AND METHODS: All women who underwent vaginal mesh repair
from 2004 to 2014 were retrospectively reviewed. Data on patients'
characteristics, presenting symptoms, treatment and outcomes were collected from
their medical records. RESULTS: A total of 741 women underwent vaginal mesh
repairs, of whom 47 had mesh erosion. The median follow-up period was 13 months
(range 3-84 months). Another nine patients with mesh erosion were referred form
other hospitals. Multivariate analysis revealed that concomitant hysterectomy
(odds ratio 27.02, 95% confidence interval 12.35-58.82; p < 0.01) and
hypertension (odds ratio 5.95, 95% confidence interval 2.43-14.49; p < 0.01) were
independent risk factors for mesh erosion. Of these 56 women, 20 (36%) were
successfully treated by conservative management, while 36 (64%) required
subsequent surgical revision. Compared with surgery, conservative treatment was
successful if the size of the erosion was smaller than 0.5 cm (p < 0.01). Six
patients (17%) had recurrent erosions after primary revision, but all
successfully healed after the second surgery. CONCLUSION: Concomitant
hysterectomy and hypertension were associated with mesh erosion. In the
management of mesh erosion, conservative treatment can be tried as the first-line
treatment for smaller erosions, while surgical repair for larger erosions.
Recurrent erosions could happen and requires repairs several times.
PMID- 28420506
TI - Prediction of spontaneous preterm delivery in asymptomatic twin pregnancies using
cervical length and granulocyte elastase.
AB - OBJECTIVE: The purpose of this study was to evaluate sonographic cervical length
(CL) and granulocyte elastase (GE) in cervical secretion as predictors of preterm
delivery in asymptomatic twin pregnancies. MATERIALS AND METHODS: This study
prospectively enrolled asymptomatic twin pregnancies with CL < 25 mm at 22-29
weeks of gestation. All women were hospitalized for preterm labor, and the
cervical secretion was obtained for GE testing on admission. The results of CL
measurement and GE testing were reviewed, and the relationship between each
variables and preterm delivery prior to 34 weeks of gestation was assessed.
RESULTS: Overall, we included 54 women with twin pregnancies, of which 12 (22.2%)
had preterm deliveries prior to 34 weeks of gestation. A CL of <20 mm was
significantly associated with preterm delivery with an odds ratio of 4.88 (95%
confidence limit, 1.15-20.73). GE was not an independent predictive marker for
preterm delivery. We also performed a subgroup analysis on the combination of CL
and GE for predicting preterm delivery. Among the patients with GE(-), CL < 20 mm
markedly increased the risk of preterm delivery with an odds ratio of 10.89 (95%
confidence limit, 1.40-77.10). CL was not associated with preterm delivery among
those with GE(+). Those with negative GE and shorter CL demonstrated the shortest
duration of pregnancy after admission. CONCLUSION: The combination of sonographic
CL and GE of cervical secretion is useful to predict the risk of preterm delivery
in asymptomatic twin pregnancies.
PMID- 28420507
TI - Asymptomatic pyuria in pregnant women during the first trimester is associated
with an increased risk of adverse obstetrical outcomes.
AB - OBJECTIVE: Urinalysis is included in the prenatal examination in the first
trimester in Taiwan, in contrast to Western countries. We aimed to investigate
whether asymptomatic pyuria as detected by urinalysis was associated with adverse
perinatal outcomes. MATERIALS AND METHODS: A total of 1187 singleton pregnant
women who received prenatal care at Kaohsiung Chang Gung Memorial Hospital
between January 2012 and December 2013 were included for retrospective analysis.
We defined asymptomatic pyuria as the presence of 15 or more white blood
cells/MUL in midstream urine without symptoms. Adverse perinatal outcomes
including preterm delivery, preterm premature rupture of membrane, low birth
weight, and Apgar scores were analyzed. Univariate and multivariate logistic
regression analyses were used to identify independent predictors. RESULTS: The
prevalence of asymptomatic pyuria was 21.3% in our cohort. Univariate analysis
showed that pyuria was the only factor associated with preterm delivery before 36
weeks of pregnancy, preterm premature rupture of membrane, and low birth weight.
In multivariate analysis, both pyuria (odds ratio: 4.89, 95% confidence interval:
1.80-13.25, p=0.002) and a maternal age of 35 years or older (odds ratio: 3.46,
95% confidence interval: 1.11-10.78, p=0.033) were significant independent
predictors for a low 5 minute Apgar score (<7). CONCLUSION: The identification of
asymptomatic pyuria via urinalysis in the first trimester may be a predictor for
adverse perinatal outcomes.
PMID- 28420508
TI - A promising protein responsible for overactive bladder in ovariectomized mice.
AB - OBJECTIVE: Ovariectomy (OVX) in mice is a model mimicking a neuro-electronic
proof of an overactive bladder in postmenopausal women. Overactive bladder (OAB)
was recently found to be due to an altered gap junction protein in a rat model.
Thus, this study was conducted to evaluate changes in cell junction protein
expression and composition in the bladder of OVX mice. MATERIALS AND METHODS:
Thirty-six virgin female mice were randomized into three groups: mice with a sham
operation only (control), OVX mice without estradiol (E2) replacement, and OVX
mice with E2 replacement (OVX + E2). Cystometry assessment was conducted and cell
junction-associated protein zonula occludens-2 (ZO-2) expression was measured
after 8 weeks. Voiding interval values (time between voids) were assessed in mice
under anesthesia. After measurements, the bladders were removed for proteomic
analysis using the label-free quantitative proteomics and liquid chromatography
mass spectrometry technology. Lastly, immunohistochemistry (IHC) and Western blot
were used to confirm the location and level, respectively, of ZO-2 expression.
RESULTS: We identified 73 differentially expressed proteins in the bladder of OVX
mice. The OVX mice showed significantly lower voiding interval values. Voiding
interval values were significantly higher in the OVX + E2 group than in the OVX
group. Urothelial thicknesses in the bladder were also significantly lower in the
OVX group than in the control group. E2 replacement reversed the urothelium
layers. Additionally, the expression of ZO-2, a tight junction protein, was the
most affected by OVX treatment. IHC and Western blot confirmed the downregulation
of ZO-2 in the bladder of OVX mice. Expression of ZO-2 protein was significantly
increased in OVX + E2 group compared with OVX group. CONCLUSION: This exploratory
study estimated changes in protein expression and composition in the bladder of
OVX mice. These changes may be associated with the molecular mechanisms of OAB.
PMID- 28420509
TI - Effect of a gymnastics program on sleep characteristics in pregnant women.
AB - OBJECTIVE: The quality and quantity of sleep represent important health issues in
pregnant women. Sleep disturbances could be associated, beyond alteration of
quality of life, with poor pregnancy outcome. Our aim was to investigate the
effect of a regular, specific, medium-term physical training program on sleep
characteristics in healthy pregnant women. MATERIALS AND METHODS: A total of 132
healthy pregnant women, with gestational age between 18 weeks and 22 weeks, were
enrolled in a prospective study. They were allocated into two groups; the first
group involved 79 women (average age, 29.4 years) who performed a specific
gymnastics program of 10 weeks, and the second group involved 53 pregnant women
(average age, 27.9 years) who did not perform gymnastics. All participants
completed a comprehensive questionnaire at baseline and after 10 weeks concerning
general data, sleep characteristics, and psycho-emotional status. The changes
arising within a diverse set of characteristics were followed and compared for
the two groups using parametric and nonparametric statistics. RESULTS: In the
control group, we observed significant worsening of 12 out of the 14 studied
parameters during the 10-week period. In comparison with the women who did not
perform gymnastics, women who performed specific gymnastics showed the following
characteristics: (1) significantly less deterioration of psycho-emotional status
(stress and anxiety levels); (2) the same general pattern of decrease in sleep
quality, which is related to the progression of pregnancy; and (3) a significant
attenuation of the worsening of several sleep characteristics, such as restless
sleep, snoring, diurnal tiredness, and excessive daytime sleepiness. Nocturnal
and diurnal sleep quantity increased significantly in both groups. CONCLUSION:
The 10-week training program designed for pregnant women has an overall
beneficial effect on sleep characteristics, not by improving them but by
attenuating their general deterioration related to the progression of pregnancy.
Our data strengthen the general recommendation regarding participation of
pregnant women in specific exercise programs, mainly for maintaining their psycho
emotional and general well-being.
PMID- 28420510
TI - Gene set-based analysis of mucinous ovarian carcinoma.
AB - OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon subtype of epithelial
ovarian cancers, and the pathogenesis is still poorly understood because of its
rarity. We conducted a gene set-based analysis to investigate the pathogenesis of
MOC by integrating microarray gene expression datasets based on the regularity of
functions defined by gene ontology or canonical pathway databases. MATERIALS AND
METHODS: Forty-five pairs of MOC and normal ovarian tissue sample gene expression
profiles were downloaded from the National Center for Biotechnology Information
Gene Expression Omnibus database. The gene expression profiles were converted to
the gene set regularity indexes by measuring the change of gene expression
ordering in a gene set. Then the pathogenesis of MOC was investigated with the
differences of function regularity with the gene set regularity indexes between
the MOC and normal control samples. RESULTS: The informativeness of the gene set
regularity indexes was sufficient for machine learning to accurately recognize
and classify the functional regulation patterns with an accuracy of 99.44%. The
statistical analysis revealed that the GTPase regulators and receptor tyrosine
kinase erbB-2 (ERBB2) were the most important aberrations; the exploratory factor
analysis revealed phosphoinositide 3-kinase-activating kinase, G-protein coupled
receptor pathway, oxidoreductase activity, immune response, peptidase activity,
regulation of translation, and transport and channel activity were also involved
in the pathogenesis of MOC. CONCLUSION: Investigating the pathogenesis of MOC
with the functionome provided a comprehensive view of the deregulated functions
of this disease. In addition to GTPase regulators and ERBB2, a plenty of
deregulated functions such as phosphoinositide 3-kinase, G-protein coupled
receptor pathway, and immune response also participated in the interaction
network of MOC pathogenesis.
PMID- 28420511
TI - Prenatal diagnosis and molecular cytogenetic characterization of concomitant
familial small supernumerary marker chromosome derived from chromosome 4q (4q11.1
q13.2) and 5q13.2 microdeletion with no apparent phenotypic abnormality.
AB - OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic
characterization of concomitant familial small supernumerary marker chromosome 4
[sSMC(4)] derived from 4q11.1-q12 and q13.2, and 5q13.2 microdeletion with no
apparent phenotypic abnormality. MATERIALS AND METHODS: A 32-year-old woman
underwent amniocentesis at 21 weeks of gestation because of absent nasal bone on
fetal ultrasound. Amniocentesis revealed a karyotype of 47,XX,+mar[13]/46,XX[3].
Array comparative genomic hybridization analysis on the cultured amniocytes
revealed a 2.752-Mb duplication at 4q11-q12, a 1.949-Mb duplication at 4q13.2,
and a 1.65-Mb deletion at 5q13.2. The woman underwent repeat amniocentesis at 24
weeks of gestation for molecular cytogenetic characterization. The phenotypically
normal parents and their elder son underwent genetic analysis. RESULTS: At repeat
amniocentesis, interphase fluorescence in situ hybridization analysis on
uncultured amniocytes revealed 79.25% (84/106) mosaicism for the sSMC(4), and
metaphase fluorescence in situ hybridization analysis on cultured amniocytes
revealed that all 20 cells examined (100%) had the sSMC(4). Polymorphic DNA
marker analysis on uncultured amniocytes excluded uniparental disomy 4. The
father had a karyotype of 47,XY,+mar[2]/46,XY[38], and interphase fluorescence in
situ hybridization revealed 2.91% (3/103) mosaicism for the sSMC(4) in his
peripheral blood. The mother carried the 5q13.2 microdeletion. The elder son had
a karyotype of 47,XY,+mar[27]/ 46,XY[13] with duplications of 4q11-q12 and
4q13.2. A 3105 g female baby was delivered at term with no apparent phenotypic
abnormality. CONCLUSION: Prenatal diagnosis of concomitant sSMC and microdeletion
should raise a suspicion of familial inheritance.
PMID- 28420512
TI - Managing vulvovaginal hematoma by arterial embolization as first-line hemostatic
therapy.
AB - OBJECTIVE: A puerperal vulvovaginal hematoma may continue to grow after a
surgical procedure and may require blood transfusion. Thus, we selected arterial
embolization for hemostasis as the first-line management in two cases of large
vulvovaginal hematoma. MATERIALS AND METHODS: Case 1 was a 32-year-old pregnant
woman. After delivery, a 10-cm vulvar hematoma developed. An enhanced computed
tomography (CT) scan revealed active bleeding. Arterial embolization was
performed and complete hemostasis was obtained. Case 2 was a 34-year-old woman
with a recurring hematoma after delivery. An enhanced CT scan revealed
extravasation in the hematoma. Gelatin sponges were applied and complete
hemostasis was obtained. In both cases, arterial embolization was successful
without requiring blood transfusions. RESULTS AND CONCLUSION: We successfully
managed two cases of puerperal vulvovaginal hematoma by arterial embolization
based on the evaluation of an enhanced CT scan. In conclusion, we suggest
arterial embolization to be a viable option for first-line treatment in the
management of vulvovaginal hematomas.
PMID- 28420513
TI - Euchromatic variants of 8q21.2 in twins.
AB - OBJECTIVE: Euchromatic variants (EVs) of 8q21.2 are extremely rare chromosomal
abnormalities. So, far there have only been two reports on EVs of 8q21.2. Here,
we report an 8q21.2 EV detected in cultured amniotic-fluid cells of twins. It was
later found to be inherited from the mother, who did not present with abnormal
phenotypes. CASE REPORT: A pregnant woman underwent amniocentesis at 16 weeks of
gestation because of advanced maternal age. This pregnancy was monozygotic twins
conceived naturally. A cytogenetic analysis of cultured amniocytes revealed
46,XY,?dup(8)(q21.2). Chromosomal microarray revealed no abnormalities. C-banding
and fluorescent in situ hybridization using chromosome 8 painting probe suggested
euchromatic nature of the extra chromosomal band. Karyotyping of the parents
showed that the EV was inherited from the mother. CONCLUSION: Many, but not all,
EVs are clinically innocuous. This is the first case of 8q21.2 EV reported in the
ethnic Han. More cases are needed to clarify whether 8q21.2 duplication as a bona
fide EV.
PMID- 28420514
TI - Detection of mosaic 15q11.1-q11.2 deletion encompassing NBEAP1 and POTEB in a
fetus with diffuse lymphangiomatosis.
AB - OBJECTIVE: We present cytogenetic and molecular cytogenetic diagnoses of mosaic
deletion of chromosome 15q11.1-q11.2 in a fetus with diffuse lymphangiomatosis.
CASE REPORT: A 33-year-old woman underwent amniocentesis at 22 weeks of gestation
because of fetal diffuse lymphangiomatosis involving left-side chest, abdominal
cavity, thigh and vulva, and intrauterine growth restriction. Amniocentesis
revealed a karyotype of 46,XX,del(15) (q11.1q11.2)[9]/46,XX[26]. The mother had a
karyotype of 46,XX. The father had a karyotype of 46,XY. The parents elected to
terminate the pregnancy. A 610-g female fetus was delivered at 23 weeks of
gestation with large cystic lymphangioma over the left abdomen, thigh, and vulva.
The umbilical cord had a karyotype of 46,XX,del(15)(q11.1q11.2)[24]/ 46,XX[16].
The placental tissue had a karyotype of 46,XX,del(15)(q11.1q11.2)[23]/ 46,XX[17].
Array comparative genomic hybridization analysis of the umbilical cord and
placenta revealed a 2.42-Mb deletion of 15q11.1-q11.2 encompassing the genes of
NBEAP1 and POTEB. CONCLUSION: Deletion of 15q11.1-q11.2 encompassing NBEAP1 and
POTEB may be associated with diffuse lymphangiomatosis.
PMID- 28420515
TI - Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a
small supernumerary marker chromosome derived from chromosome 2.
AB - OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic
characterization of mosaicism for a small supernumerary marker chromosome (sSMC)
derived from chromosome 2. CASE REPORT: A 42-year-old woman underwent
amniocentesis at 17 weeks of gestation because of advanced maternal age.
Amniocentesis revealed a karyotype of 47,XY,+mar[10]/46,XY[12]. The parental
karyotypes were normal. Array comparative genomic hybridization analysis of the
DNA extracted from cultured amniocytes revealed no genomic imbalance. Spectral
karyotyping analysis failed to identify the sSMC. Metaphase fluorescence in situ
hybridization analysis using the satellite probes CEP1/5/19, CEP2, CEP3, CEP4,
CEP6, CEP7, CEP8, CEP9, CEP10, CEP12, CEP13/21, CEP14/22, CEP15, CEP16, and CEP20
revealed a result of 47,XY,+mar .ish der(2)(D2Z+)[10]. The sSMC was derived from
the alpha satellite of chromosome 2. Polymorphic DNA marker analysis using the
markers specific for chromosome 2 on the DNAs extracted from cultured amniocytes
and parental bloods excluded uniparental disomy 2. At 39 weeks of gestation, a
healthy 3394-g male baby was delivered with no phenotypic abnormality. The cord
blood had a karyotype of 47,XY,+mar[21]/46,XY[19]. CONCLUSION: Array comparative
genomic hybridization and spectral karyotyping may fail to detect an sSMC derived
from alpha satellite, which needs satellite probes for confirmation.
PMID- 28420516
TI - Prenatal diagnosis and molecular cytogenetic characterization of low-level mosaic
trisomy 12 at amniocentesis associated with a favorable pregnancy outcome.
AB - OBJECTIVE: We present prenatal diagnosis of low-level mosaic trisomy 12. CASE
REPORT: A 40-year-old woman underwent amniocentesis at 18 weeks of gestation
because of advanced maternal age, which revealed a karyotype of
47,XX,+12[5]/46,XX[24] consistent with 17.2% (5/29) mosaicism for trisomy 12.
Repeat amniocentesis performed at 21 weeks of gestation revealed a karyotype of
47,XX,+12[4]/46,XX[6] consistent with 40% (4/10) mosaicism for trisomy 12.
Interphase fluorescence in situ hybridization (FISH) on 112 uncultured amniocytes
detected 23 cells with trisomy 12 consistent with 20.5% (23/112) mosaicism for
trisomy 12. Polymorphic DNA marker analysis excluded uniparental disomy 12. Array
comparative genomic hybridization (aCGH) on uncultured amniocytes revealed a
result of arr 12p13.33q24.33 (230,451-133,773,499) * 2.2, 17p12 (14,191,925
15,442,037) * 1.0 consistent with 10-20% mosaic trisomy 12. The father carried
the 17p12 microdeletion. The fetal ultrasound findings were unremarkable. A 3958
g female fetus was delivered at 37 weeks of gestation with no phenotypic
abnormality. The cord blood had a karyotype of 46,XX. Postnatal interphase FISH
on urinary cells revealed 7.14% (7/98) mosaicism for trisomy 12. CONCLUSION: Low
level mosaic trisomy 12 at amniocentesis can be associated with a favorable
pregnancy outcome. Interphase FISH and aCGH on uncultured amniocytes are useful
for confirmation of low-level mosaic trisomy 12 at amniocentesis.
PMID- 28420517
TI - Ileocecal endometriosis: diagnosis and management.
AB - OBJECTIVE: Ileocecal endometriosis is rare. Symptoms range from no symptoms,
cramps, vomiting, to acute intestinal obstruction. Our objective was to review
our cases, clarify, and resume its most appropriate management focusing on the
factors to determine diagnosis. This is a retrospective study by revision of
medical charts of all ileal endometriosis cases of our unit from 2006 to 2014.
CASE REPORT: Seven cases were found; three (43%) had previous endometriosis
laparoscopic diagnosis, four (57%) had partial bowel obstruction episodes, three
(43%) had chronic pelvic pain, and one developed acute intestinal obstruction in
postoperative ileostomy closure. In three (43%), the diagnosis was made with
magnetic resonance imaging (MRI) and double contrast barium enema, in one (14%)
only with MRI, and the other three (43%) during surgery. All patients underwent
resection of the ileum and evolved favorably. CONCLUSION: Variability in symptoms
hinders diagnosis. The gold standard for diagnosis is MRI, but clinical suspicion
optimizes imaging test diagnosis. Segmental resection should be indicated in the
majority of the cases.
PMID- 28420518
TI - Acute small bowel obstruction caused by barbed suture on the second day after
laparoscopic hysterosacropexy: A case report and literature review.
AB - OBJECTIVE: To report a case of small bowel obstruction caused by barbed suture
applied in hysterosacropexy, and possible solutions. CASE REPORT: A 57-year-old
woman underwent laparoscopic hysterosacropexy for a Stage 2 uterine prolapse,
presenting with acute abdominal pain and a bowel obstruction syndrome 2 days
following the surgery. Conservative treatment was given, but the symptoms did not
improve and gradually became worse. Diagnostic laparoscopy was performed on the
7th day after the hysterosacropexy, and the volvulus was found. The residual end
of the barbed V-Loc adopted in the peritoneal closure was incidentally hooked to
the mesentery and caused small bowel obstruction. The redundant V-Loc was
released and cut off at 2 cm. Neither bowel ischemia nor significant bowel injury
was noted. Two days later, she was discharged without complication. CONCLUSION: A
barbed suture has a risk of bowel obstruction when used in surgery. To avoid a
grave prognosis, early diagnosis and prompt management of complication is
necessary.
PMID- 28420519
TI - Simultaneous cul-de-sac and tubal pregnancy following in vitro fertilization.
AB - OBJECTIVE: The aim of this study is to share a valuable experience of heterotopic
pregnancy following in vitro fertilization. CASE REPORT: A 37-year-old, gravida
3, para 2 (cesarean section 2 times), woman underwent in vitro fertilization with
three embryos transferred. On Day 23 after the embryo transfer, right tubal
pregnancy with a 0.7-cm gestational sac was found by ultrasound, and her serum
beta-human chorionic gonadotropin level was 81,388 mIU/mL. She underwent a
laparotomy with right salpingectomy. On Day 43 after the embryo transfer,
intermittent abdominal pains developed. A live fetus with a crown-rump length of
2.0 cm was found in the cul-de-sac. Under the diagnosis of abdominal pregnancy,
she was admitted for sona-guided KCl and methotrexate injections. She received
four units of packed red blood cells due to a drop in hemoglobin level from 12.5
g/dL to 8.6 g/dL. The patient recovered well, and the serum beta-human chorionic
gonadotropin declined to <10 mIU/mL. CONCLUSION: Various forms of ectopic
pregnancy should be kept in mind in early pregnancy following in vitro
fertilization.
PMID- 28420520
TI - The association of enchondromatosis with malignant transformed chondrosarcoma and
ovarian juvenile granulosa cell tumor (Ollier disease).
AB - OBJECTIVE: Ovarian juvenile granulosa cell tumor has an interesting association
with multiple enchondromatosis (Ollier disease and Maffucci syndrome) and should
be considered a leading diagnosis when an ovarian mass is found in young patients
with these conditions. Besides the association with nonskeletal malignancies,
there is a high risk of malignant transformation of enchondroma in chondrosarcoma
as was also the case in this instance. CASE REPORT: The report uses multiple
images to document the representative and characteristic markers of multiple
enchondromas in a 22-year-old patient with Ollier disease complicated by
malignant transformation of chondrosarcoma and in whom the disease is associated
with ovarian juvenile granulosa cell tumor of the right ovary. CONCLUSION: It is
important to recognize that when the female patient presents with
enchondromatosis and a large unilateral multilocular-solid ovarian mass, the
specific diagnosis of granulosa cell tumor can be made with high accuracy.
PMID- 28420521
TI - Delayed postcoital vaginal cuff dehiscence with small bowel evisceration after
robotic-assisted staging surgery.
AB - OBJECTIVE: We report a rare case of vaginal cuff dehiscence with small bowel
evisceration at 7 months post robotic-staging surgery. CASE REPORT: A 41-year-old
woman was sent to the emergency room with sudden onset of abdominal pain, vaginal
bleeding, and vaginal protruding mass after sexual activity. She had a history of
synchronous uterine and ovarian cancer treated with robotic-staging surgery 7
months before. Then she received six courses of postoperative adjuvant
chemotherapy, and the last chemotherapy ended 1 month ago. At the operation room,
some small bowel loops were noted in the vaginal tip with cuff dehiscence and
bleeding. After repositioning of the small bowel, a 2.5-cm vaginal cuff
dehiscence was repaired transvaginally. The patient recovered well, and is free
of disease and has normal sexual activity 2 months after repairs. CONCLUSION:
Unusual delayed-type vaginal cuff dehiscence hints the possibility that a
combination of robotic surgery and postoperative chemotherapy might result in
delayed healing of the vaginal cuff.
PMID- 28420522
TI - Successful treatment of gestational trophoblastic neoplasia in the uterine cornus
with laparoscopic cornuostomy and postoperative methotrexate injection.
AB - OBJECTIVE: Management of cornual gestational trophoblastic neoplasia (GTN) has
never been reported. Here, we describe the first case of cornual GTN. CASE
REPORT: A 32-year-old woman was diagnosed with left cornual GTN after evacuation
of a complete mole. Laparoscopic cornuostomy was performed with intramural
vasopression injection and barbed sutures. Histopathology revealed hydropic
chorionic villi. Complete hydatidiform mole was diagnosed, and treated with
adjuvant methotrexate, to address the poor decline of beta-human chorionic
gonadotropin levels during follow-up. The beta- human chorionic gonadotropin
levels declined to < 1 mIU/mL 9 months after cornuostomy. She successfully
conceived 16 months after cornuostomy, and underwent cesarean section at 37
gestational weeks due to concomitant severe preeclampsia. CONCLUSION: Cornual GTN
can be successfully managed with laparoscopic cornuostomy and adjuvant
methotrexate.
PMID- 28420523
TI - Molecular cytogenetic characterization and prenatal diagnosis of familial Xp22.33
microdeletion encompassing short stature homeobox gene in a male fetus with a
favorable outcome.
PMID- 28420524
TI - Prenatal diagnosis of mosaicism for trisomy 15 in a single colony at
amniocentesis with a favorable fetal outcome.
PMID- 28420525
TI - Sclerotherapy for placenta accreta: Some concerns.
PMID- 28420526
TI - Response to the comments of Dr Shigeki Matsubara.
PMID- 28420527
TI - Corrigendum to "First trimester combined test for Down syndrome screening in
unselected pregnancies - A report of a 13-year experience" [Taiwan J Obstet
Gynecol 52 (4) (2013) 523-526].
PMID- 28420528
TI - Two-dimensional gas chromatography with electron capture detection for the
analysis of atmospheric ozone depleting halocarbons.
AB - This study is to develop a GC*GC method with electron capture detection (ECD) to
analyze atmospheric halocarbons in the concentration range of parts per trillion
by volume (pptv). To enrich atmospheric halocarbons a home-built thermal
desorption (TD) device was coupled to the GC*GC-ECD. The technique of flow
modulation was adopted using a Deans switch for GC*GC. Several column
combinations of first and second dimensions were tested and the column set of DB
5*TG-1301 was found to show the best orthogonality for halocarbons. A series of
modulation parameters were tested for their optimal settings. The modulation
period (PM) was found to have minimal wrap-around when set at 3s. The modulation
ratio (MR) was determined to be 7.82 to ensure reproducible results and maximum
sensitivity. The modulation duty cycle (DC) was calculated to be approximately
0.17. Nine halocarbons were separated successfully and seven were calibrated with
the use of a certified standard gas mixture. The correlation coefficients (R2)
were greater than 0.9972. The reproducibility was better than 1.90% as expressed
in relative standard deviation (RSD; N=30) and the detection limits were in the
range of pptv for the target halocarbons. A field test by continuous analyzing
ambient air with hourly resolution was performed to show the stability of the
method as suggested by the homogeneity of certain halocarbons, while also
reflecting concentration variation for others when emissions did arise.
PMID- 28420529
TI - Separation of antibody monomer-dimer mixtures by frontal analysis.
AB - The removal of aggregates, particularly soluble dimers, from monoclonal
antibodies (mAbs) remains a persistent challenge in downstream processing. In
this work, we have examined the separation of an antibody monomer from its dimer
on the cation exchange resin Nuvia HR-S (Bio-Rad Laboratories) using frontal
analysis. In this process, a mixture of monomer and dimer is continuously fed to
the column under conditions where the mixture is favorably bound, resulting in
two breakthrough fronts whose monomer and dimer compositions are determined by
the multi-component equilibrium and kinetics of the system. Experimentally, the
selectivity for dimer was found to vary substantially with ionic strength, being
lowest when conditions favor the strongest binding, and increasing to a maximum
at intermediate ionic strengths where rapid exchange with the bound monomer can
occur. A mechanistic model is developed to describe the competitive binding
frontal analysis process, assuming pore diffusion and a significant kinetic
resistance to binding as a function of ionic strength. The model was solved
numerically and was able to describe both the frontal analysis processes and
batch adsorption experimental data, accounting for process parameters such as
feed composition and salt concentration. The resulting model can be used to
optimize column operating conditions for yield and purity.
PMID- 28420530
TI - Rapid determination of the various native forms of vitamin B6 and B2 in cow's
milk using ultra-high performance liquid chromatography.
AB - As the formation of pyridoxal phosphate, the active cofactor of vitamin B6, is
dependent on riboflavin 5-phosphate, we propose a fast and simple ultra-high
performance liquid chromatography method for the simultaneous determination of
the native B6 vitamers pyridoxal, pyridoxine, pyridoxamine, their mono phosphorus
esters and 4-pyridoxic acid as well as vitamin B2 as riboflavin and its
phosphorus ester riboflavin 5-phosphate in milk. Separation was achieved under
6.0min by reversed-phase and pH gradient elution. Sample preparation was
optimized regarding various acids and pH levels. Changes in those parameters led
to significant deviations of sample matrix breakdown efficiency. The optimized
method was then validated regarding specificity, accuracy, precision, linearity,
range, detection and quantification limits. As the method performed satisfactory,
is was used to study commercial liquid cow's milk (n=31), regarding effects of
the employed preservation technique (pasteurization, extended shelf-life, ultra
high temperature) on the composition and content of B6 and B2 vitamers. In cow's
milk, vitamin B6 mostly consists of pyridoxal and its phosphate ester, with
pyridoxal phosphate being the bulk component. The catabolite of the vitamin B6
metabolism, 4-pyridoxic acid was present in significant amounts in all studied
samples, with up to 2.69MUmolL-1. Vitamin B2 was present as riboflavin and its
phosphate ester up to 12.86MUmolL-1.
PMID- 28420531
TI - High-throughput determination of vancomycin in human plasma by a cost-effective
system of two-dimensional liquid chromatography.
AB - Therapeutic drug monitoring (TDM) is one of the most important services of
clinical laboratories. Two main techniques are commonly used: the immunoassay and
chromatography method. We have developed a cost-effective system of two
dimensional liquid chromatography with ultraviolet detection (2D-LC-UV) for high
throughput determination of vancomycin in human plasma that combines the
automation and low start-up costs of the immunoassay with the high selectivity
and sensitivity of the liquid chromatography coupled with mass spectrometric
detection without incurring their disadvantages, achieving high cost
effectiveness. This 2D-LC system offers a large volume injection to provide
sufficient sensitivity and uses simulated gradient peak compression technology to
control peak broadening and to improve peak shape. A middle column was added to
reduce the analysis cycle time and make it suitable for high-throughput routine
clinical assays. The analysis cycle time was 4min and the peak width was 0.8min.
Compared with other chromatographic methods that have been developed, the
analysis cycle time and peak width for vancomycin was reduced significantly. The
lower limit of quantification was 0.20MUg/mL for vancomycin, which is the same as
certain LC-MS/MS methods that have been recently developed and validated. The
method is rapid, automated, and low-cost and has high selectivity and sensitivity
for the quantification of vancomycin in human plasma, thus making it well-suited
for use in hospital clinical laboratories.
PMID- 28420532
TI - Predictive Protein Toxicity and Its Use in Risk Assessment.
AB - In the EU novel proteins used in food or feed are assessed for their potential
toxic effects in humans and livestock animals. The discovery of clear molecular
features linked to the toxicity of a protein may be an important step towards the
use of predictive protein toxicity in risk assessment.
PMID- 28420533
TI - Observer-based consensus of networked thrust-propelled vehicles with directed
graphs.
AB - In this paper, we investigate the consensus problem for networked underactuated
thrust-propelled vehicles (TPVs) interacting on directed graphs. We propose
distributed observer-based consensus protocols, which avoid the reliance on the
measurements of translational velocities and accelerations. Using the input
output analysis, we present necessary and sufficient conditions to ensure that
the observer-based protocols can achieve consensus for both the cases without and
with constant communication delays, provided that the communication graph
contains a directed spanning tree. Simulation examples are finally provided to
illustrate the effectiveness of the control schemes.
PMID- 28420534
TI - Adaptive compensation control for attitude adjustment of quad-rotor unmanned
aerial vehicle.
AB - A compensation control strategy based on adaptive back-stepping technique is
presented to address the problem of attitude adjustment for a quad-rotor unmanned
aerial vehicle (QR- UAV) with inertia parameter uncertainties, the limited
airflow disturbance and the partial loss of rotation speed effectiveness. In the
design process of control system, adaptive estimation technique is introduced
into the closed loop system in order to compensate the lumped disturbance term.
More specifically, the designed controller utilizes "prescribed performance
bounds" method, and therefore guarantees the transient performance of tracking
errors, even in the presence of the lumped disturbance. Adaptive compensation
algorithms under the proposed closed loop system structure are derived in the
sense of Lyapunov stability analysis such that the attitude tracking error
converge to a small neighborhood of equilibrium point. Finally, the simulation
results demonstrate the effectiveness of the proposed controller.
PMID- 28420535
TI - Technique for myocardial protection in pulmonary atresia intact ventricular
septum.
PMID- 28420536
TI - Malperfusion rather than merely timing of operative repair determines early and
late outcome in type A aortic dissection.
AB - BACKGROUND: Although generally better outcomes are reported in patients
undergoing early repair of type A aortic dissection, patients who survive the
first 48 hours self-select themselves toward better outcomes as well.
Malperfusion is another important determinant of outcome in these patients. The
aim of this study was to examine the hypothesis that malperfusion, not the timing
of operation, is the dominant determinant of outcome in repair of type A aortic
dissection. METHODS: A total of 205 patients underwent operative repair of acute
type A aortic dissection in our hospital over a 17-year period. The time from
symptom onset to surgical repair was reliably established in 152 cases. Patients
were grouped into those who had undergone surgery within 12 hours of symptom
onset (early surgery group; n = 72 [47%]) and those who underwent surgery beyond
12 hours of symptom onset (late surgery group; n = 80 [53%]). RESULTS: Thirty-day
mortality was similar in the 2 groups (early surgery: 19.4% [95% confidence
interval [CI] 12.0%-30.6%]; late surgery: 13.8% [95% CI, 7.9%-23.5%]; P = .08).
The log-rank test for equality of survivor functions was 0.08. However,
malperfusion with hemodynamic compromise was more common in the early surgery
group (47% vs 31%; P = .029) and was identified as an independent predictor of
long-term mortality (hazard ratio, 2.65; 95% CI, 1.21-5.79; P = .014).
CONCLUSIONS: Malperfusion at presentation rather than timing of intervention is
the major risk factor of death both in the hospital and at long-term follow-up in
patients undergoing surgery for type A aortic dissection.
PMID- 28420537
TI - Bilateral versus unilateral antegrade cerebral perfusion in total arch
replacement for type A aortic dissection.
AB - BACKGROUND: Antegrade cerebral perfusion (ACP) is the most widely used cerebral
protection strategy for complex aortic repair and includes unilateral (u-ACP) and
bilateral (b-ACP) techniques. The superiority of b-ACP over u-ACP has been the
subject of much debate. Focusing on type A aortic dissection requiring total arch
replacement, we investigated the clinical effects of b-ACP versus u-ACP. METHODS:
Between September 2006 and August 2014, 203 patients presenting with type A
aortic dissection (median age, 51.0 +/- 13 years; range, 17-72 years; 128 males)
underwent total aortic arch replacement with hypothermic circulatory arrest. ACP
was used in all patients, including u-ACP in 82 (40.3%) and b-ACP in 121 (59.7%).
RESULTS: There was no significant difference between the u-ACP and b-ACP groups
in terms of cardiopulmonary bypass (CPB) time, cross-clamp time, or circulatory
arrest time. Overall 30-day mortality was comparable in the 2 groups (11.6% for b
ACP vs 20.7% for u-ACP; P = .075). The prevalence of postoperative permanent
neurologic dysfunction (PND) was comparable as well (8.4% vs 16.9%; P = .091).
Mean ventilation time was lower in the b-ACP group (95.5 +/- 45.25 hours vs 147.0
+/- 82 hours; P < .001). Mean lengths of stay in the intensive care unit and the
hospital overall were comparable in the 2 groups (intensive care unit: 16 +/-
17.75 days vs 17 +/- 11.5 days, P = .454; hospital: 26.5 +/- 20.6 days vs 24.8 +/
10.3 days, P = .434). The P values from logistic regression models indicated
that in the 2 groups combined, CPB time and circulatory arrest time were
independent risk factors for both mortality and PND. CONCLUSIONS: In this, the
first published study focusing on the efficacy of u-ACP and b-ACP in total arch
replacement for type A aortic dissection, the b-ACP group did not demonstrate
significantly lower 30-day mortality or PND rate compared with the u-ACP group.
Future large-sample studies are warranted to thoroughly examine this critical
issue.
PMID- 28420538
TI - The impact on productivity of a hypothetical tax on sugar-sweetened beverages.
AB - OBJECTIVES: To quantify the potential impact of an additional 20% tax on sugar
sweetened beverages (SSBs) on productivity in Australia. METHODS: We used a multi
state lifetable Markov model to examine the potential impact of an additional 20%
tax on SSBs on total lifetime productivity in the paid and unpaid sectors of the
economy. The study population consisted of Australians aged 20 years or older in
2010, whose health and other relevant outcomes were modelled over their remaining
lifetime. RESULTS: The SSBs tax was estimated to reduce the number of people with
obesity by 1.96% of the entire population (437,000 fewer persons with obesity),
and reduce the number of employees with obesity by 317,000 persons. These effects
translated into productivity gains in the paid sector of AU$751 million for the
working-age population (95% confidence interval: AU$565 million to AU$954
million), using the human capital approach. In the unpaid sector, the potential
productivity gains amounted to AU$1172 million (AU$929 million to AU$1435
million) using the replacement cost method. These productivity benefits are in
addition to the health benefits of 35,000 life years gained and a reduction in
healthcare costs of AU$425 million. CONCLUSIONS: An additional 20% tax on SSBs
not only improves health outcomes and reduces healthcare costs, but provides
productivity gains in both the paid and unpaid sectors of the economy.
PMID- 28420539
TI - HTA and decision-making processes in Central, Eastern and South Eastern Europe:
Results from a survey.
AB - OBJECTIVE: To gain knowledge and insights on health technology assessment (HTA)
and decision-making processes in Central, Eastern and South Eastern Europe
(CESEE) countries. METHODS: A cross-sectional study was performed. Based on the
literature, a questionnaire was developed in a multi-stage process. The
questionnaire was arranged according to 5 broad domains: (i) introduction/country
settings; (ii) use of HTA in the country; (iii) decision-making process; (iv)
implementation of decisions; and (v) HTA and decision-making: future challenges.
Potential survey respondents were identified through literature review-with a
total of 118 contacts from the 24 CESEE countries. From March to July 2014, the
survey was administered via e-mail. RESULTS: A total of 22 questionnaires were
received generating an 18.6% response rate, including 4 responses indicating that
their institutions had no involvement in HTA. Most of the CESEE countries have
entities under government mandates with advisory functions and different
responsibilities for decision-making, but mainly in charge of the reimbursement
and pricing of medicines. Other areas where discrepancies across countries were
found include criteria for selecting technologies to be assessed, stakeholder
involvement, evidence requirements, use of economic evaluation, and timeliness of
HTA. CONCLUSIONS: A number of CESEE countries have created formal decision-making
processes for which HTA is used. However, there is a high level of heterogeneity
related to the degree of development of HTA structures, and the methods and
processes followed. Further studies focusing on the countries from which
information is scarcer and on the HTA of health technologies other than medicines
are warranted. CLASSIFICATION: Reviews/comparative analyses.
PMID- 28420540
TI - What do we mean when we talk about the Triple Aim? A systematic review of
evolving definitions and adaptations of the framework at the health system level.
AB - Notwithstanding important contributions of the Triple Aim, uncritical enthusiasm
regarding the implications of the framework may be leading to inconsistent use,
particularly when applied at the health system level, which goes beyond the
original positioning of the framework as a strategic organizing principle to
guide improvement initiatives at the organizational or local community level. We
systematically identified uses of the Triple Aim that extended beyond its
original intention to focus on uses at the whole health system level, to assess
convergence and divergence with the original definition. We also attempted to
identify consistencies in the way the Triple Aim was adapted for different
contexts and settings. Data sources were indexed databases, web search engines,
and international experts. Forty-seven articles were included in the analysis. We
found that the definition of the Triple Aim has been subject to important
modifications when the framework is used to define goals for whole health care
systems or globally. Despite widespread recognition of the name, what constitutes
the Triple Aim framework varies. We identified the need to consider the inclusion
of at least two additional aims of health care systems - the provider experience
of care, and the desire to achieve health equity for populations.
PMID- 28420541
TI - Stability of Lisfranc injury fixation in Thiel Cadavers: Is routine fixation of
the 1st and 3rd tarsometatarsal joint necessary?
AB - BACKGROUND: There is debate as to whether a home run screw (medial cuneiform to
2nd metatarsal base) combined with k-wire fixation of the 4th & 5th
tarsometatarsal joints is sufficient to stabilise Lisfranc injuries or if
fixation of the 1st and 3rd tarsometatarsal joints is also required. Unlike the
2nd, 4th and 5th tarsometatarsal joints, stabilisation of the 1st and 3rd
requires either intra-articular screw or an extra-articular plate which risk
causing chondrolysis and/or osteoarthritis. The aims of this cadaveric study were
to determine if routine fixation of the 1st and 3rd tarsometatarsal joints is
necessary and to determine if a distal to proximal home run screw is adequate.
METHODS: Using 8 Theil-embalmed specimens, measurements of tarsometatarsal joint
dorsal displacement at each ray (1st-5th) and 1st-2nd metatarsal gaping were made
during simulated weight bearing with sequential ligamentous injury and
stabilisation to determine the contribution of anatomical structures and fixation
to stability. RESULTS: At baseline, mean dorsal tarsometatarsal joint
displacement of the intact specimens during simulated weight bearing (mm) was:
1st: 0.14, 2nd: 0.1, 3rd:0, 4th: 0, 5th: 0.14. The 1st-2nd intermetatarsal gap
was 0mm. After transection of the Lisfranc ligament only, there was 1st-2nd
intermetatarsal gaping (mean 4.5mm), but no increased dorsal displacement. After
additional transection of all the tarsometatarsal joint ligaments, dorsal
displacement increased at all joints (1st: 4.5, 2nd: 5.1, 3rd: 3.6, 4th: 2, 5th:
1.3). Stabilisation with the home run screw and 4th and 5th ray k-wires virtually
eliminated all displacement. Further transection of the inter-metatarsal
ligaments increased mean dorsal displacement of the 3rd ray to 2.5mm. K-wire
fixation of the 3rd ray completely eliminated dorsal displacement. CONCLUSIONS:
The results of this cadaveric study suggest that stabilising the medial cuneiform
to the 2nd metatarsal base combined with stabilisation of the 4th and 5th
tarsometatarsal joints with K-wires will stabilise the 1st and 3rd
tarsometatarsal joints if the inter-metatarsal ligaments are intact. Thus 3rd
TMTJ stability should be checked after stabilising the 2nd and 4/5th. Provided
the intermetatarsal ligaments (3rd-4th) are intact, the 3rd ray does not need to
be routinely stabilised.
PMID- 28420542
TI - Improving prehospital trauma care in Rwanda through continuous quality
improvement: an interrupted time series analysis.
AB - INTRODUCTION: Injury is a major cause of premature death and disability in East
Africa, and high-quality pre-hospital care is essential for optimal trauma
outcomes. The Rwandan pre-hospital emergency care service (SAMU) uses an
electronic database to evaluate and optimize pre-hospital care through a
continuous quality improvement programme (CQIP), beginning March 2014. MATERIALS
AND METHODS: The SAMU database was used to assess pre-hospital quality metrics
including supplementary oxygen for hypoxia (O2), intravenous fluids for
hypotension (IVF), cervical collar placement for head injuries (c-collar), and
either splinting (splint) or administration of pain medications (pain) for long
bone fractures. Targets of >90% were set for each metric and daily team meetings
and monthly feedback sessions were implemented to address opportunities for
improvement. These five pre-hospital quality metrics were assessed monthly before
and after implementation of the CQIP. Met and unmet needs for O2, IVF, and c
collar were combined into a summative monthly SAMU Trauma Quality Scores (STQ
score). An interrupted time series linear regression model compared the STQ score
during 14 months before the CQIP implementation to the first 14 months after.
RESULTS: During the 29-month study period 3,822 patients met study criteria.
1,028 patients needed one or more of the five studied interventions during the
study period. All five endpoints had a significant increase between the pre-CQI
and post-CQI periods (p<0.05 for all), and all five achieved a post-CQI average
of at least 90% completion. The monthly composite STQ scores ranged from 76.5 to
97.9 pre-CQI, but tightened to 86.1-98.7 during the post-CQI period. Interrupted
time series analysis of the STQ score showed that CQI programme led to both an
immediate improvement of +6.1% (p=0.017) and sustained monthly improvements in
care delivery-improving at a rate of 0.7% per month (p=0.028). CONCLUSION: The
SAMU experience demonstrates the utility of a responsive, data-driven quality
improvement programme to yield significant immediate and sustained improvements
in pre-hospital care for trauma in Rwanda. This programme may be used as an
example for additional efforts engaging frontline staff with real-time data
feedback in order to rapidly translate data collection efforts into improved care
for the injured in a resource-limited setting.
PMID- 28420543
TI - Serum persistent organic pollutants (POPs) and prostate cancer risk: A case
cohort study.
AB - It is still unclear whether persistent organic pollutants (POPs) exposure
increases the prostate cancer incidence risk. This prospective cohort study
evaluated the associations between serum POPs concentrations and prostate cancer
risk. Within a case-cohort study, we identified 110 people diagnosed with
prostate cancer and randomly selected 256 sub-cohort participants without
prostate cancer. Serum concentrations of 32 polychlorinated biphenyl (PCB)
congeners and 19 organochlorine pesticides (OCPs) were measured. The hazard
ratios (HRs) and 95% confidence interval (95% CI) for determining the
associations between POPs and risk of prostate cancer were estimated using the
weighted Cox regression model. Compared to the lowest tertile, increased risks of
prostate cancer incidence were observed in the upper tertile of following PCBs:
the moderately chlorinated (HR: 4.19; 95% CI: 1.30-13.54), the highly chlorinated
(HR: 4.14; 95% CI: 1.75-9.79), biologically persistent as CYP1A and CYP2B
inducers (HR: 4.44; 95% CI: 1.33-14.83), the sum of non- dioxin-like (HR: 3.47;
95% CI: 1.21-9.98), and ?PCBs (HR: 4.29; 95% CI: 1.52-12.08). In dose-response
curves, ?PCBs was associated with the increased risk of prostate cancer. Our
findings suggested a possible role of POPs in the etiology of prostate cancer.
PMID- 28420544
TI - Disclosing Agents for the Intraoperative Identification of Biofilms on Orthopedic
Implants.
AB - BACKGROUND: Disclosing agents are dyes used in dentistry to colorize plaque
(biofilm) and may offer a means for intraoperative detection of biofilms on
orthopedic implants. Methylene blue (MB) stains biofilm and is safely used in
orthopedic applications. Injection of MB into acutely infected prosthetic knees
before debridement may enable visualization of biofilm, which could influence
treatment decisions. The aims of this study were to determine if MB could be used
to visualize biofilm on total knee arthroplasty (TKA) implants and to determine
if MB staining has an antimicrobial effect that might interfere with subsequent
culture. METHODS: Staphylococcus epidermidis biofilms were formed on TKA
polyethylene liners and polymethylmethacrylate (PMMA) and Teflon discs. After
staining biofilms on these implants, the bacterial densities were determined
through sonication and quantitative culture. The antimicrobial activity of MB
staining was determined by measuring the bacterial density of S. epidermidis
biofilms on PMMA discs incubated in 0.05% MB for 24 hours vs 30 seconds and
comparing it with controls unexposed to MB. RESULTS: MB stained S. epidermidis
biofilms grown on TKA implants and Teflon and PMMA discs in vitro. Sonication and
quantitative culture of the stained implants showed that bacterial densities were
at supraphysiological levels. Staining did not affect the ability to culture the
organism. CONCLUSION: MB is a possible cost-effective and novel method to
expeditiously identify intraoperative biofilm. To further evaluate MB staining
and its potential clinical usefulness, future studies are needed to assess the
ability of MB to stain physiological levels of biofilm.
PMID- 28420545
TI - GQSAR modeling and combinatorial library generation of 4-phenylquinazoline-2
carboxamide derivatives as antiproliferative agents in human Glioblastoma tumors.
AB - BACKGROUND: TSPO translocator protein, encoded in humans by the Tspo gene plays a
crucial role in mitochondria mediated apoptosis and necrotic cell death through
its association with Mitochondrial Permeability Transition pore (MPTP). It has
been shown that this function can be exploited as a potential treatment for human
Glioblastoma Multiforme. In this study, a novel robust fragment based QSAR model
has been developed for a series of 4-phenylquinazoline-2-carboxamides
experimentally known to be ligands for TSPO, thus triggering apoptotic mechanism
cascade. RESULTS: Model developed showed satisfactory statistical parameters for
the experimentally reported dataset (r2=0.8259, q2=0.6788, pred_r2=0.8237 and F
test=37.9). Low standard error values (r2_se=0.253, q2_se=0.34, pred_r2_se=0.14)
confirmed the accuracy of the generated model. The model obtained had 4
descriptors, namely, R1-Volume, R2-SsCH3E-index, R3-SsCH3count and R5-EpsilonR.
Two of them had positive contribution while the other two had negative
correlation. CONCLUSION: The high binding affinity and the presence of essential
structural features in these compounds make them an ideal choice for the
consideration as potent anti-GBM drugs. Activity predicted by GQSAR model
reinforces their potential as worthy candidates for drugs against GBM. The
detailed analysis carried out in this study provides a substantial basis for the
prospective design and development of novel 4-phenylquinazoline-2-carboxamide
compounds as TSPO ligands capable of inducing apoptosis in cancer cells.
PMID- 28420546
TI - Facilitating Fresh: State Laws Supporting School Gardens Are Associated With Use
of Garden-Grown Produce in School Nutrition Services Programs.
AB - OBJECTIVE: To examine whether state laws are associated with the presence of
school gardens and the use of garden-grown produce in school nutrition services
programs. DESIGN: Nationally representative data from the School Health Policies
and Practices Study 2014 were combined with objectively coded state law data
regarding school gardens. MAIN OUTCOME MEASURES: Outcomes were: (1) the presence
of a school garden at each school (n = 419 schools), and (2) the use of garden
grown items in the school nutrition services program. ANALYSIS: Multivariate
logistic regression was used to examine each outcome. Contextual covariates
included school level, size, locale, US Census region, student race/ethnic
composition, and percentage of students eligible for free and reduced-priced
meals. RESULTS: State law was not significantly associated with whether schools
had a garden, but it was associated with whether schools used garden-grown items
in nutrition services programs (odds ratio, 4.21; P < .05). Adjusted prevalence
of using garden-grown items in nutrition services programs was 15.4% among
schools in states with a supportive law, vs 4.4% among schools in states with no
law. CONCLUSIONS AND IMPLICATIONS: State laws that support school gardens may
facilitate the use of garden-grown items in school nutrition service programs.
Additional research is needed regarding the types of messaging that might be most
effective for motivating school administrators to appreciate the value of school
gardens. In addition, another area for further research pertains to scaling
garden programs for broader reach.
PMID- 28420547
TI - Types and Characteristics of Fish and Seafood Provisioning Scripts Used by Rural
Midlife Adults.
AB - OBJECTIVE: To examine rural New York State consumers' cognitive scripts for fish
and seafood provisioning. DESIGN: A cross-sectional design with in-depth,
semistructured interviews. SETTING: Three rural New York State counties.
PARTICIPANTS: Adults (n = 31) with diverse fish-related experiences were
purposefully recruited. PHENOMENON OF INTEREST: Scripts describing fish and
seafood acquisition, preparation, and eating out. ANALYSIS: Interview transcripts
were coded for emergent themes using Atlas.ti. Diagrams of scripts for each
participant were constructed. RESULTS: Five types of acquisition scripts included
quality-oriented, price-oriented, routine, special occasion, and fresh catch.
Frequently used preparation scripts included everyday cooking, fast meal,
entertaining, and grilling. Scripts for eating out included fish as first choice,
Friday outing, convenient meals, special event, and travel meals. Personal values
and resources influenced script development. Individuals drew on a repertoire of
scripts based on their goals and resources at that time and in that place. Script
characteristics of scope, flexibility, and complexity varied widely. CONCLUSIONS
AND IMPLICATIONS: Scripts incorporated goals, values, and resources into routine
food behaviors. Understanding the characteristics of scripts provided insights
about fish provisioning and opportunities to reduce the gap between current
intake and dietary guidelines in this rural setting.
PMID- 28420548
TI - Expression of long non-coding RNAs in autoimmunity and linkage to enhancer
function and autoimmune disease risk genetic variants.
AB - Genome-wide association studies have identified numerous genetic variants
conferring autoimmune disease risk. Most of these genetic variants lie outside
protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also
differentially expressed in autoimmune disease but their regulation is also
unclear. The majority of the human genome is transcribed yet its biologic
significance is incompletely understood. We performed whole genome RNA-sequencing
[RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs
[lncRNAs] in leukocytes from subjects with autoimmune disease and identified
annotated and novel lncRNAs differentially expressed across multiple disorders.
We found that loci transcribing novel lncRNAs were not randomly distributed
across the genome but co-localized with leukocyte transcriptional enhancers,
especially super-enhancers, and near genetic variants associated with autoimmune
disease risk. We propose that alterations in enhancer function, including lncRNA
expression, produced by genetics and environment, change cellular phenotypes
contributing to disease risk and pathogenesis and represent attractive
therapeutic targets.
PMID- 28420549
TI - Predictors of Left Ventricular Functional Recovery and Their Impact on Clinical
Outcomes in Patients With Newly Diagnosed Dilated Cardiomyopathy and Heart
Failure.
AB - BACKGROUND: To identify the predictors of left ventricular functional recovery
(LVFR) and its impacts on clinical outcomes in acute heart failure (AHF) patients
with newly diagnosed dilated cardiomyopathy (DCM). METHODS: A total of 175
consecutive patients with newly diagnosed DCM and AHF were divided into two
groups according to LVFR on FU echocardiography; the recovered group (n=54,
54.3+/-18.5years, 31 males) vs. the non-recovered group (n=121, 60.5+/-15.1years,
79 males). Clinical, laboratory, and echocardiographic findings were compared,
and major adverse cardiac and cerebrovascular events (MACCE) including death,
rehospitalisation, and stroke were analysed. RESULTS: Left ventricular function
(LV) was normalised in 54 patients (30.8%) on follow-up echocardiography. The
change in the level of N-terminal pro-B-type natriuretic peptide (DeltaNT-proBNP)
between initial presentation and discharge >1633.5pg/mL was an independent
predictor of LVFR, whereas diabetes and LV end-systolic diameter >50mm were
negative predictors of LVFR on multivariate analysis. During five years of
clinical follow-up, MACCE developed in 91 patients: 58 deaths, 29
rehospitalisations, and 4 strokes. On multivariate analysis, baseline LVEF <30%
and no LVFR were independent predictors of MACCE. CONCLUSION: Left ventricular
functional recovery was not uncommon in newly diagnosed DCM with AHF. The changes
in NT-proBNP level during hospitalisation, diabetes, and larger initial LV size
were independent predictors of LVFR, and LVFR was an independent predictor of
future MACCE. Serial monitoring of NT-proBNP and LV function would be useful in
the risk stratification of newly diagnosed DCM with AHF.
PMID- 28420550
TI - Effect of a moderate caffeine dose on endurance cycle performance and
thermoregulation during prolonged exercise in the heat.
AB - OBJECTIVES: This study investigated the influence of a moderate caffeine dose on
endurance cycle performance and thermoregulation during prolonged exercise in
high ambient temperature. DESIGN: Double-blind cross-over study. METHODS: Eight
healthy, recreationally active males (mean+/-SD; age: 22+/-1 years; body mass:
71.1+/-8.5kg; VO2peak: 55.9+/-5.8mLkg-1min-1; Wmax: 318+/-37W) completed one
VO2peak test, one familiarisation trial and two experimental trials. After an
overnight fast, participants ingested a placebo or a 6mgkg-1 caffeine dose 60min
before exercise. The exercise protocol consisted of 60min of cycle exercise at
55% Wmax, followed by a 30min performance task (total kJ produced) in 30 degrees
C and 50% RH. RESULTS: Performance was enhanced (Cohen's d effect size=0.22) in
the caffeine trial (363.8+/-47.6kJ) compared with placebo (353.0+/-49.0kJ;
p=0.004). Caffeine did not influence core (p=0.188) or skin temperature (p=0.577)
during exercise. Circulating prolactin (p=0.572), cortisol (p=0.842) and the
estimated rates of fat (p=0.722) and carbohydrate oxidation (p=0.454) were also
similar between trial conditions. Caffeine attenuated perceived exertion during
the initial 60min of exercise (p=0.033), with no difference in thermal stress
across trials (p=0.911). CONCLUSIONS: Supplementation with 6mgkg-1 caffeine
improved endurance cycle performance in a warm environment, without
differentially influencing thermoregulation during prolonged exercise at a fixed
work-rate versus placebo. Therefore, moderate caffeine doses which typically
enhance performance in temperate environmental conditions also appear to benefit
endurance performance in the heat.
PMID- 28420551
TI - Is There an Accurate Pre-operative Criterion for Dialysis Access Artery or Vein
diameter?
PMID- 28420552
TI - Commentary on "Five Year Natural History of Screening Detected Sub-Aneurysms and
Abdominal Aortic Aneurysms in 70 Year Old Women and Systematic Review of Repair
Rate in Women".
PMID- 28420553
TI - Incidence of respiratory viral infections and associated factors among children
attending a public kindergarten in Taipei City.
AB - BACKGROUND: Kindergarteners frequently encounter various infectious diseases, so
surveillance of viral infectious diseases would provide information for their
health promotion. METHODS: We enrolled kindergarten attendees, age 2-5 years,
during the academic years of 2006 and 2007 in a Taipei City kindergarten. Daily
monitoring of illness and regular biweekly physical examinations were undertaken.
Multiple infections were defined as one child having two or more laboratory
confirmed viral infections with different viruses or different serotypes during
one academic year. RESULTS: The overall laboratory-confirmed incidence rate of
respiratory viral infection was 239 per 100 person-years in the 2006 academic
year and 136 per 100 person-years in the 2007 academic year. The attack rate for
seasonal influenza was 17% in the 2006 academic year and 27% in the 2007 academic
year. Boys and children with allergies had significantly higher risks to get
multiple viral infections [odds ratio (OR) 1.81, 95% confidence interval (CI)
1.20-2.75; OR 1.56, 95% CI 1.00-2.39, respectively]. Boys also tended to get
enterovirus infections (OR 1.56, 95% CI 1.02-2.38) while children with allergies
tended to acquire adenovirus infections (OR 1.71, 95% CI 1.12-2.66). CONCLUSION:
Boys and children with allergies were more susceptible to multiple viral
infections, so they should be more cautious about viral infections.
PMID- 28420554
TI - The incidence and clinical associated factors of interval colorectal cancers in
Southern Taiwan.
AB - BACKGROUND/PURPOSE: Interval colorectal cancer (CRC) is an emerging issue in CRC
screening and surveillance. The frequency of interval CRC and its associated
factors have not been well studied in Eastern Asia. We aim to clarify the factors
associated with interval CRC. METHODS: CRC patients who had negative colonoscopy
results 6-36 months prior to cancer diagnosis were defined as cases of interval
CRC. Patient characteristics, past history, colon preparation, colonoscopy
findings, and pathology were retrospectively evaluated. A total of 670 patients
with colorectal adenocarcinoma by pathology who also underwent colonoscopy before
diagnosis from January 2005 to November 2014 were recruited. RESULTS: Twenty-two
(3.28%) patients (65.7 +/- 9.2 years old; 9 male) were diagnosed with interval
CRC. The interval CRCs were predominantly located at the rectum and cecum, and
presented as earlier stage cancers (Stage I and Stage II: 86.4%, Stage III and
Stage IV: 13.6%). Factors associated with interval cancer include end-stage renal
disease (ESRD) (hazard ratio: 10.494, 95% confidence interval: 2.131-51.681) and
shorter ascending colon withdrawal time (interval cancer: noninterval cancer
2.00+/-0.82: 4.91+/-3.74 minutes; hazard ratio: 0.561, 95% confidence interval:
0.345-0.913). Prior polypectomy and tumor size also tended to be related to
interval CRC. CONCLUSION: The prevalence of interval CRC in the present study is
3.28%. Comorbidity with ESRD and shorter ascending colon withdrawal time could be
factors associated with interval CRC. Good colon preparation for the patients
with ESRD and more ascending colon withdrawal time could reduce the interval CRC.
PMID- 28420555
TI - Chemoembolization for Hepatocellular Carcinoma in Patients with Extrahepatic
Spread: Prognostic Determinants and Appropriate Candidates.
AB - PURPOSE: To investigate treatment outcome, prognostic factors for overall
survival, and appropriate candidates for transarterial chemoembolization among
patients with hepatocellular carcinoma (HCC) and extrahepatic spread (EHS).
MATERIALS AND METHODS: From January 2010 to June 2014, 111 consecutive patients
with HCC and EHS treated by transarterial chemoembolization alone were evaluated.
Factors associated with overall survival were evaluated using Cox regression
analysis, and a scoring equation was established to subgroup patients with EHS.
RESULTS: Median follow-up was 3.8 months, and median overall survival was 3.8
months (95% confidence interval [CI], 2.9-4.7 months). Multivariate analysis
demonstrated maximum tumor size >= 10 cm (hazard ratio [HR] 1.58; 95% CI, 1.02
2.46; P = .041), multifocal intrahepatic tumors (HR 1.55; 95% CI, 1.03-2.33; P =
.037), and portal vein tumor thrombosis (PVTT) (HR 1.81; 95% CI, 1.12-2.91; P =
.015) as significant predictors of overall survival. Based on these factors, a
scoring equation was developed to predict treatment outcome of transarterial
chemoembolization, with an area under the receiver operating characteristic curve
of 0.76 in predicting 6-month survival. Using a cutoff score of 5.5, patients
with HCC and EHS were divided into 2 groups with significantly different overall
survival (8.1 months for EHS1 and 2.4 months for EHS2; P < .001). The described
method of subgrouping remained discriminatory regardless of baseline
characteristics. CONCLUSIONS: Maximum tumor size, intrahepatic tumor
distribution, and presence of PVTT were significant determinants of overall
survival for patients with HCC and EHS. Transarterial chemoembolization may be
appropriate for patients with EHS but lower intrahepatic tumor burden.
PMID- 28420556
TI - Can paddock scale data integration achieve more cost effective outcomes in the
Great Barrier Reef? A case study in the Fitzroy Basin.
AB - The decline in health of the Great Barrier Reef and the pressure on allocating
funds efficiently has increased efforts to prioritise where public funds are
invested. The Fitzroy basin and coastal catchments is 152,000 square kilometres
and geographically diverse. Past work has identified that sediment loads leaving
the catchment are posing a high risk to the ongoing health of the Reef and that
there is a need to prioritise funds to achieve cost effective outcomes. In this
paper we aim to present an alternative approach to effective prioritisation of
sediment reductions. The approach integrates spatial information regarding the
sediment source and process, levels of adoption, bare ground cover, and cost into
a function to rank neighbourhood catchments. The results demonstrate the
complexity of the issue and the challenge the Fitzroy Basin Association faces
when allocating funds. They also illustrate that there are effective
opportunities in particular priority areas within the catchment in which on
ground actions could be undertaken, proving it to be a useful approach in
prioritising future investments aimed at achieving cost effective sediment
reductions to the Reef.
PMID- 28420557
TI - Temporal and Spatial View of Jasmonate Signaling.
AB - The jasmonate signaling pathway has been established for 10 years. Nonetheless,
two recent reports suggest that its temporal and spatial regulation is worth
further investigation. These reports show that jasmonate responses decay
gradually with increasing plant age and that signaling components vary between
different tissues.
PMID- 28420558
TI - Maternal Medical Complexity: Impact on Prenatal Health Care Spending among Women
at Low Risk for Cesarean Section.
AB - BACKGROUND: Obstetric procedures are among the most expensive health care
services, yet relatively little is known about health care spending among
pregnant women, particularly the commercially-insured. OBJECTIVE: The objective
of this study was to examine the association between maternal medical complexity,
as a result of having one or more comorbid conditions, and health care spending
during the prenatal period among a national sample of 95,663 commercially-insured
women at low risk for cesarean delivery. METHODS: We conducted secondary analyses
of 2010-2011 inpatient, outpatient, and professional claims for health care
services from the Health Care Cost Institute. Allowed charges were summed for the
prenatal and childbirth periods. Ordinary least squares regressions tested
associations between maternal health conditions and health care expenditures
during pregnancy. RESULTS: Thirty-four percent of pregnant women had one or more
comorbidities; 8% had two or more. Pregnant women with one or more comorbidities
had significantly higher allowed charges than those without comorbidities (p <
.001). Spending during the prenatal period was nearly three times higher for
women with preexisting diabetes compared with women with no comorbid conditions.
Average levels of prenatal period spending associated with maternal comorbidities
were similar for women who had vaginal and cesarean deliveries. Patient
characteristics accounted for 30% of the variance in prenatal period
expenditures. CONCLUSIONS: The impact of maternal comorbidities, and in
particular preexisting diabetes, on prenatal care expenditures should be taken
into account as provider payment reforms, such as pay-for performance incentives
and bundled payments for episodes of care, extend to maternal and child health
related services.
PMID- 28420559
TI - Recent trends in the prevalence of underweight, overweight, and obesity in Korean
adults: The Korean National Health and Nutrition Examination Survey from 1998 to
2014.
AB - BACKGROUND: Recent obesity studies have reported that the rising trend in obesity
has stabilized or leveled off. Our study aimed to update estimates of the recent
prevalence trend in obesity based on the Korean National Health and Nutrition
Examination Survey 1998-2014. METHODS: A total of 66,663 subjects were included
and defined as being either underweight, overweight, or obese, in accordance with
a BMI of 18.5 kg/m2 or lower, 23 kg/m2 or higher, and 25 kg/m2 or higher,
respectively. RESULTS: The prevalence of underweight in KNHANES I through VI
surveys was 4.7%, 3.3%, 3.4%, 3.3%, 2.7%, and 2.6%, respectively, in men (P for
trend = 0.03, beta = -0.002) and 5.4%, 6.1%, 5.8%, 6.5%, 7.6%, and 7.5%,
respectively, in women (P for trend = 0.04, beta = 0.003). Also for KNHANES I
through VI, the respective prevalence of overweight/obesity was 50.3%, 57.2%,
62.5%, 62.3%, 61.4%, and 62.3% in men (p for trend<0.01, beta = 0.009) and 48.3%,
50.3%, 50.0%, 47.8%, 47.0%, and 45.3% in women (p for trend<0.01, beta = -0.01),
respectively. CONCLUSIONS: The obesity occurrence in men was trending upward with
respect to overweight/obesity and for grade 1 and 2 obesity, but not for
abdominal obesity. However, the obesity trends in women were leveling off from
overweight/obesity, grade 1 obesity, and abdominal obesity measures. Further
studies are required with data on muscle mass and adiposity for effective obesity
control policies.
PMID- 28420560
TI - Does revision of resection margins based on frozen section improve overall
survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma? A
meta-analysis.
AB - BACKGROUND: Margin status is the main surgical determinant of long-term outcome
in pancreatic cancer. Intraoperative frozen section (IOFS) detects microscopic
positive margins at a stage when margin revision is possible. The aim of this
study was to determine if IOFS driven-revision of pancreatic resection margin(s)
improves overall survival (OS) in pancreatic cancer. METHODS: A systematic review
of major reference databases was undertaken. Patients were divided into 3 groups
based on initial FS (FSR0 for negative margin and FSR1 for positive microscopic
margin) and final Permanent Section report (PSR0 for negative margin and PSR1 for
positive microscopic margin): Group 1 (FSR0 -> PSR0), Group 2 (FSR1 -> PSR0), and
Group 3 (FSR1 -> PSR1). Patients in Groups 2 and 3 had surgical revision of the
FSR1 margin. Data was meta-analysed. RESULTS: 4 studies included in the final
analysis. No difference in OS and incidence of lymph node metastases between
Groups 2 and 3 (P = 0.590 and P = 0.410). CONCLUSIONS: IOFS-based revision of R1
pancreatic resection margin does not improve OS, even when it results in an R0
margin. This suggests that any benefit of margin revision based on FS is over
ridden by markers of more advanced or aggressive disease.
PMID- 28420561
TI - Response to Gentile S et al.: Risk factors for severe hypoglycaemia in people
with insulin-treated diabetes: Are we sure we took into account all variables
involved?
PMID- 28420562
TI - Progression of untreated mild thoracic Scheuermann's kyphosis - Radiographic and
functional assessment after mean follow-up of 46 years.
AB - BACKGROUND: There is no data available on the radiographic development of the
Scheuermann's deformity. Our purpose was to investigate radiographic deformity
progression and the relation between kyphosis progression and clinical outcome in
patients with untreated Scheuermann's kyphosis. METHODS: Thoracic kyphosis (Th4
Th12) was measured from standing lateral radiographs in 19 patients at baseline
and after mean 46-year follow-up. Mean age at baseline was 19.2 and at follow-up
64.7 years. At follow-up, height, weight, hand grip strength, and hamstring
tightness were measured, and sit-to-stand and walking tests were performed.
Additionally general health and quality of life questionnaires were administered.
RESULTS: The mean thoracic kyphosis increased from 46 degrees (range 25 degrees
78 degrees ) at baseline to 60 degrees (34 degrees -82 degrees ) (p < 0.001) at
follow-up. Mean of the vertebrae wedge increased from 8.8 degrees to 9.9 degrees
(p = 0.046). There was no correlation between extent of kyphosis progression and
function at follow-up. CONCLUSIONS: Among patients with Scheuermann's disease the
degree of radiographic deformity progressed slightly during long-term follow-up.
Progression did not predict symptoms.
PMID- 28420563
TI - Compassion, Mindfulness, and the Happiness of Healthcare Workers.
AB - CONTEXT: Decreased well-being of healthcare workers expressed as stress and
decreased job satisfaction influences patient safety, patient satisfaction, and
cost containment. Self-compassion has garnered recent attention due to its
positive association with well-being and happiness. Discovering novel pathways to
increase the well-being of healthcare workers is essential. OBJECTIVE: This study
sought to explore the influence of self-compassion on employee happiness in
healthcare professionals. DESIGN, SETTING, AND PARTICIPANTS: A total of 400
participants (mean age = 45 +/- 14, 65% female) healthcare workers at a large
teaching hospital were randomly asked to complete questionnaires assessing their
levels of happiness and self-compassion, life conditions, and habits. MEASURES:
Participants completed the Happiness Scale and Self-Compassion Scales, the Five
Facet Mindfulness Questionnaire as well as variables associated with well-being:
relationship status, the number of hours spent exercising a week, attendance at a
wellness facility, and engagement in a regular spiritual practice. RESULTS: Self
compassion was significantly and independently associated with perceived
happiness explaining 39% of its variance after adjusting for age, marital status,
gender, time spent exercising, and attendance to an exercise facility. Two
specific subdomains of self-compassion from the instrument used, coping with
isolation and mindfulness, accounted for 95% of the self-compassion effect on
happiness. CONCLUSION: Self-compassion is meaningfully and independently
associated with happiness and well-being in healthcare professionals. Our results
may have practical implications by providing specific self-compassion components
to be targeted in future programs aimed at enhancing well-being in healthcare
professionals.
PMID- 28420564
TI - Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Primary Non-muscle-invasive
Bladder Cancer.
AB - INTRODUCTION: The purpose of this study was to assess the role of pretreatment
neutrophil-to-lymphocyte ratio (NLR) as a predictor of clinical outcomes in
patients treated with transurethral resection (TURB) for primary non-muscle
invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Data from 918 patients
treated with TURB for primary NMIBC were retrospectively collected. NLR was
evaluated as binary variable with the cut-point of 3 based on the visual best
correlation of the receiver operating curve analyses focusing on disease
recurrence. The median follow-up was 62 months. Cox regression analyses were used
to evaluate associations with recurrence (RFS) and progression-free survival
(PFS). Subgroup analyses were done according to risk groups and receipt of
intravesical bacillus Calmette-Guerin therapy. RESULTS: Overall, 293 patients had
a NLR >= 3. High NLR was associated with pathologic T stage and smoking status.
The 5-year RFS and PFS for NLR < 3 and NLR >= 3 were, respectively, 55.5% versus
45.9% (P = .01) and 94.9% versus 89.9% (P = .004). On multivariable analyses, NLR
>= 3 remained significantly associated with RFS and PFS. The addition of NLR
increased the discrimination of a multivariable model by 0.6% and 2.3% for RFS
and PFS, respectively. Moreover, NLR showed a trend in the association with
outcomes in patients treated with intravesical bacillus Calmette-Guerin therapy.
CONCLUSIONS: Integration of NLR in a prediction model could be helpful in
predicting RFS and PFS in patients with primary NMIBC and identifying those who
are likely to fail therapy and may benefit from an early radical cystectomy.
Limitations are associated to the retrospective design.
PMID- 28420566
TI - The role of antithrombin in patients with toxic epidermal necrolysis.
PMID- 28420565
TI - Analysis of prognostic factors for acute kidney injury with continuous renal
replacement therapy in severely burned patients.
AB - BACKGROUND: Acute kidney injury (AKI) is a critical complications in severely
burned patients associated with high morbidity and mortality. The purpose of this
study was to investigate the impact of severity of AKI at the time of continuous
renal replacement therapy (CRRT) start on patient outcome and to identify the
prognostic factors in severely burned patients with CRRT application. METHODS:
From January 2007 to June 2010, 84 burn patients with more than 40% of total body
surface area (TBSA) burned who treated with continuous renal replacement therapy
for acute kidney injury were analyzed retrospectively. RESULTS: There was no
significant difference of mortality by the severity of AKI at the time of CRRT
start. However, the mean TBSA burned, abbreviated burn severity index, arterial
pH, partial pressure of carbon dioxide (PaCO2) and blood urea nitrogen
(BUN)/creatinine (Cr) ratio had a statistical significance to predict mortality
in receiver operation characteristic curve. In a multivariate logistic regression
analysis, only sepsis had an independent association with mortality. CONCLUSIONS:
The severity of the AKI at the time of CRRT start did not have significant
relationship with patient outcome. CRRT can be applied to minimize the
complication of AKI including electrolyte imbalance and volume overload. Because
only the presence of sepsis was independently associated with mortality,
treatment for sepsis should be focused to improve the survival of the severely
burned patients with CRRT.
PMID- 28420567
TI - A draft of bronchoscopic grading system in patients with toxic epidermal
necrolysis.
PMID- 28420568
TI - Gender-specific differences and burn outcome.
PMID- 28420569
TI - Identification of factors predicting scar outcome after burn in adults: A
prospective case-control study.
AB - This study examined influences on scarring after burn in a prospective study
using a defined outcome measure: scar height measured by a modified Vancouver
Scar Scale (mVSS). A prospective case-control study was conducted among 616 adult
subjects who sustained a burn in Western Australia. Patient factors influencing
scar outcome including gender, Fitzpatrick skin type and selected co-morbidities
were explored, as well as injury and clinical factors. A logistic regression
model for raised scar after burn was developed which achieved an overall correct
prediction rate of 81.1%; 74.8% for those with raised scar and 86.0% for those
without raised scar. From this study, injury and clinical predictors for raised
scar after adjustment for other variables are: increasing %TBSA, greater burn
depth as indicated by level of surgical intervention, wound complications and
prolonged hospital stay. Intrinsic patient predictors for raised scar in patients
with comparable injuries are: young age (<=30 years), female gender and
Fitzpatrick skin types 4-6. The strength of association statistics (odds ratios
and 95% confidence intervals) reported will be of practical benefit for clinical
decision-making and counselling of patients, and plausible biological
explanations for the findings support the validity of the results.
PMID- 28420570
TI - Herpesviradae infections in severely burned children.
AB - OBJECTIVE: Burn-related immunosuppression can promote human herpesviridae
infections. However, the effect of these infections on morbidity and mortality
after pediatric burn injuries is unclear. METHODS: We retrospectively analyzed
pediatric patients with burns >=10% of the total body surface area (TBSA) who
were admitted between 2010 and 2015. On clinical suspicion of a viral infection,
antiviral therapy was initiated. Viral infection was confirmed via Tzanck smear,
viral culture, and/or PCR. Study endpoints were mortality, days of antiviral
agent administration, type of viral test used, type of viral infection, and
length of hospitalization. RESULTS: Of the 613 patients were analyzed, 28
presented with clinically diagnosed viral infections. The use of Tzanck smears
decreased over the past 5 years, whereas PCR and viral cultures have become
standard. Patients with viral infections had significantly larger burns (53+/-15%
vs. 38+/-18%, p<0.001); however, length of stay per TBSA burn was comparable
(0.5+/-0.4 vs. 0.6+/-0.2, p=0.211). The most commonly detected herpesviridae was
herpes simplex virus 1. Two patients died due to sepsis, which was accompanied by
HSV infection. The mortality rate among all patients (2.7%) was comparable to
that in the infected group (7.1%, p=0.898). Acyclovir was given systemically for
9+/-8days (N=76) and/or topically for 9+/-9days for HSV (N=39, combination of
both N=33). Ganciclovir was prescribed in three cases for CMV. CONCLUSIONS: Viral
infections occur more commonly in patients suffering from larger burns, and HSV
infections can contribute to mortality.
PMID- 28420571
TI - Assessing guidelines for burn referrals in a resource-constrained setting:
Demographic and clinical factors associated with inter-facility transfer.
AB - AIM: The aim was to assess demographic and clinical factors associated with inter
facility referrals for patients with burns in a resource-constrained setting.
METHODS: This was a cross-sectional case review of patients presenting with a
burn at the trauma unit at the Red Cross War Memorial Children's Hospital (RXH)
in Cape Town, South Africa. RESULTS: Six hundred and eleven-(71%) children were
referred to the burns or the intensive care unit and 253 children were treated
and discharged from the trauma unit. Of those admitted as inpatients 94%
fulfilled at least one of the criteria for referral and 80% of those treated and
discharged fulfilled the criteria for referral. CONCLUSIONS: Almost three out of
four children evaluated at the trauma unit were referred to the burns unit for
further management. However, a large number of patients were treated and
discharged from the trauma unit despite being eligible for referral.
PMID- 28420572
TI - Nutritional management of cystic fibrosis - an update for the 21st century.
AB - Nutritional management is an essential part of multidisciplinary care for
infants, children and adults with cystic fibrosis (CF). In 2016 two updated
nutritional consensus guidelines were published [1,2]. This review will explore
some of the key points in the nutritional management of people with CF in the
21st Century.
PMID- 28420573
TI - Low levels of physical activity in Sudanese individuals with some features of
metabolic syndrome: Population based study.
AB - BACKGROUND: The aim of this study was to evaluate the level of physical activity
among Sudanese population. METHODS: A descriptive cross sectional study composed
of 323 participants from Khartoum state, Sudan. Data collected using pretested
designed questionnaire based on previously validated Global Physical Activity
Questionnaire. The demographic and physical measurement including blood glucose,
anthropometric and blood pressure. RESULTS: The Mean age of participants was
35.5. Males were 59.9% and females 47.1% and the prevalence of inactivity was
53.8%. Despite the fact that males are more active than females (P<0.000)
physical activity tends to decrease with age but this not statistically
significant. Physical activity is significantly decreased with obesity, higher
education and doing sedentary jobs (P<0.018, P<0.000 and P<0.000 respectively).
While majority of individuals with hypertension and pre-hypertension tend to do
less physical activity (P<0.045 and P<0.008 respectively). Logistic regression
analysis shown that gender is absolute risk factor for physical activity. Males
have more than three times probability of being physically active than women
OR3.82 (1.91-7.30). In this study, physical activity was not affected by central
obesity (P<0.497), diabetes (P<0.378) and being married or not (P<0.135).
CONCLUSION: Physical activity in Sudanese women was significantly decreased in
comparison with men.
PMID- 28420574
TI - Vitamin supplements in type 2 diabetes mellitus management: A review.
AB - Type 2 diabetes mellitus (T2DM) is a major public health challenge that affects
countries across the world. The use of pharmacological therapy is often limited
in some patients due to a loss of effect over time or development of adverse
effects such as weight gain or hypoglycaemia. This has prompted searches into the
role of non-pharmacological therapies in T2DM. The availability and use of
vitamin supplements in developed countries have increased significantly and there
is evidence that certain vitamins may have roles in the management of T2DM. This
review examines the literature assessing the use of vitamins A, C, E, D, K and
the B group vitamins (B1, B3, B7, B6, B9, B12) in the management of T2DM. No
clear evidence supporting the beneficial role of any specific vitamin in the
treatment of T2DM was found. Thus, it is recommended that until further studies
are conducted to clarify the role of such vitamins in T2DM management, they
should not be routinely recommended in clinical practice.
PMID- 28420575
TI - Correlation of various serum biomarkers with the severity of diabetic
retinopathy.
AB - : Hyperglycemia induced inflammation and angiogenic factors are implicated as a
contributor to the onset and progression of diabetic retinopathy (DR) in type 2
diabetes mellitus patients (T2DM). Tumor necrosis factor (TNF-alpha) and C
reactive protein (CRP) are inflammatory cytokines which induce retinal VEGF and
are involved in the progression of proliferative diabetic retinopathy (PDR).
Therefore the aim of the present study is to investigate the relationship between
diabetic retinopathy and systemic inflammation in patients with type 2 diabetes
mellitus. MATERIALS AND METHODS: Patients with T2DM, with or without diabetic
retinopathy were included in the study. Serum inflammatory cytokines, vascular
growth factor were studied in different stages of DR. RESULTS: Patients with T2DM
with and without diabetic retinopathy were compared. Patients with diabetic
retinopathy had increased serum levels of inflammatory cytokines CRP, TNF-alpha,
as well as VEGF compared to serum levels of diabetic patients without
retinopathy. CONCLUSION: T2DM patients with retinopathy have higher levels of
circulating inflammatory cytokines and VEGF compared to patients without
retinopathy. These proinflammatory cytokines and angiogenic factors are involved
in the progression of DR and proliferative diabetic retinopathy. The results
showed the importance of inflammation and vascular endothelial growth factor in
the progression of NPDR and PDR.
PMID- 28420576
TI - Prevalence of hypertension and prehypertension in adolescence in Ahvaz, Iran.
AB - BACKGROUND: High blood pressure is a risk factor for some disease like stroke,
coronary heart disease, and renal failure. High blood pressure in children is an
increasing health problem. OBJECTIVES: The aim of this study was to determine
prevalence of hypertension and pre-hypertension age between 10 to 17 years old.
PATIENTS AND METHODS: This descriptive analytic study was conducted using
multiphase sampling method in Ahvaz (Southwest of Iran). A questionnaire include:
height, weight, and body mass index, systolic and diastolic blood pressures
filled for each participant. Blood pressure was measured twice for each person.
For the diagnosis of hypertension, the fourth report of the Diagnosis,
Evaluation, and Treatment of High Blood Pressure in Children and Adolescents of
the National Health Institute of United States was used. RESULTS: Total
participants of the study were 1707children and adolescents including 922 boys
(54%) and 785 girls (46%). The prevalence of high blood pressure was 1.7% (2.5%
in boys and 0.8%). The prevalence of pre-hypertension was 9%(7.6% in boys, 10.6%
in girls). The mean systolic and diastolic blood pressures increased with
increasing body mass index. CONCLUSIONS: The prevalence of high blood pressure
was found to be lower than other studies in our country. The prevalence of the
high blood pressure in boys was significantly higher than girls. This study, like
other studies showed high correlation between being overweight and an increase in
systolic and diastolic blood pressure.
PMID- 28420577
TI - Effect of short-term yoga-based lifestyle intervention on plasma glucose levels
in individuals with diabetes and pre-diabetes in the community.
AB - AIM: To study the effect of short term Yoga-based lifestyle intervention in the
management of diabetes and pre-diabetes, through a 'pilot' community-based study.
METHODS: A total of 1292 subjects with diagnosed type 2 diabetes and pre-diabetes
were recruited from different States of India viz., Karnataka, Maharashtra,
Gujarat, Rajasthan, and Tamilnadu participated in the study. Yoga-based lifestyle
intervention was introduced through 10-day non-residential camps. Baseline and
post intervention assessments of fasting plasma glucose (FPG) were measured on
the first day and tenth day respectively. Of 1292 subjects, 896 both pre- and
post- FPG readings were available. Data analysis was done using statistical
package for the social sciences (SPSS), version 16. RESULTS: Mean baseline FPG
level was 133.1 (+/-47.98) and the mean post intervention FPG reduced to 121.19
(+/-40.56). There was a statistically significant decrease in FPG, p value
(<0.0001). CONCLUSION: The result suggests that a short-term Yoga-based lifestyle
intervention effectively reduces FPG levels in type 2 diabetes patients and pre
diabetes.
PMID- 28420578
TI - Metabolic syndrome and its components are related to psychological disorders: A
population based study.
AB - BACKGROUND: Psychological disorders are considered as today's one of the most
important public health problems all around the world. Another alarming
condition, which attributed to cardiovascular disease (CVD) is metabolic syndrome
(Mets). The aims of the current study were to explore (1) the prevalence of
anxiety and depression in a large representative population of Iran, and (2)
evaluate their possible association with MetS patients. METHOD: Applying a
randomized stratified-cluster approach, 9829 adults, aged 35-65 years, were
recruited as part of the MASHAD study. Socio demographic, anthropometric and
biochemical analyses were performed. Beck's anxiety inventory and Beck's
depression inventory II were applied to assessment of the degree of anxiety and
depression among the subjects. RESULTS: The prevalence of MetS, anxiety and
depression were 38.8%, 25% and 31.5%, respectively. The prevalence of these
factors was significantly (P<0.05) higher in women, compared to men and subjects
with MetS were significantly (P<0.05) associated with both anxiety and
depression. Additionally, multivariate analysis after adjusting for potential
confounders showed a significant relationship between MetS and anxiety (p=0.04).
CONCLUSION: Our data demonstrates the significant association of MetS components
with anxiety and depression and high prevalence of these co-morbidities in
adults, particularly in women.
PMID- 28420579
TI - Clustering of cardio metabolic risk factors in Iranian adult population: A
growing problem in the north of Iran.
AB - INTRODUCTION: The clustering of components of metabolic syndrome (MetS) is a
major concern in a transition population because of dramatic changing toward
modern life styles. The objective of this study was to determine the prevalence
of clustering of various combinations of MetS and its association with obesity.
METHODS AND SUBJECTS: In a population- based cross-sectional study, a
representative samples of 1000 adults were recruited in Babol, the north of Iran.
The demographic data, blood pressure, body mass index and waist circumference
(WC) were measured with standard method. Fasting blood sugar, serum levels of
triglycerides, high density lipoprotein were measured with enzymatic method.
RESULTS: A quarter of population had only one component of MetS. The prevalence
of just two components was 30.7% and 26.2% in men and women respectively and
about 67.1% of men and 73.3% of women had >=2 risk factors (P=0.001). While the
joint prevalence of three and four components was 22.0% and 12.0% in male and
27.3% and 16.5% in female respectively. The combination of high WC with any of
other four components of MetS were significantly higher compared with any other
joint combinations in particularly among women (P=0.001). The adjusted odds ratio
for having clustering (>=2 risk factors) increased 5.6 times (95%CI: 2.15, 6.04)
in obese subjects and remained at significant level after adjustment for age,
sex, level of education. CONCLUSION: An emerging high rate of clustering of joint
combination of cardio metabolic risk factors highlights an urgent intervention
for life style modification in public health management.
PMID- 28420580
TI - Comparative pharmacodynamic analysis of imidazoline compounds using rat model of
ocular mydriasis with a test of quantitative structure-activity relationships.
AB - Imidazol(in)e derivatives, having the chemical structure similar to clonidine,
exert diverse pharmacological activities connected with their interactions with
alpha2-adrenergic receptors, e.g. hypotension, bradycardia, sedation as well as
antinociceptive, anxiolytic, antiarrhythmic, muscle relaxant and mydriatic
effects. The mechanism of pupillary dilation observed after systemic
administration of imidazol(in)es to rats, mice and cats depends on the
stimulation of postsynaptic alpha2-adrenoceptors within the brain. It was proved
that the central nervous system (CNS)-localized I1-imidazoline receptors are not
engaged in those effects. It appeared interesting to analyze the CNS-mediated
pharmacodynamics of imidazole(in)e agents in terms of their chromatographic and
calculation chemistry-derived parameters. In the present study a systematic
determination and comparative pharmacometric analysis of mydriatic effects in
rats were performed on a series of 20 imidazol(in)e agents, composed of the well
known drugs and of the substances used in experimental pharmacology. The eye
pupil dilatory activities of the compounds were assessed in anesthetized Wistar
rats according to the established Koss method. Among twenty imidazol(in)e
derivatives studied, 18 produced diverse dose-dependent mydriatic effects. In the
quantitative structure-activity relationships (QSAR) analysis, the
pharmacological data (half maximum mydriatic effect - ED50 in MUmol/kg) were
considered along with the structural parameters of the agents from molecular
modeling. The theoretically calculated lipophilicity parameters, CLOGP, of
imidazol(in)es, as well as their lipophilicity parameters from HPLC, logkw, were
also considered. The attempts to derive statistically significant QSAR equations
for a full series of the agents under study were unsuccessful. However, for a
subgroup of eight apparently structurally related imidazol(in)es a significant
relationship between log(1/ED50) and logkw values was obtained. The lack of
"predictive" QSAR for the whole series of the structurally diverse agents is
probably due to a complex mechanism of the ligand-alpha2-adrenergic receptor
interactions, which are predominantly of a highly structurally specific polar
nature. Such interactions are difficult to quantify with the established chemical
structural descriptors, contrary to the less specific, molecular bulkiness
related interactions.
PMID- 28420582
TI - Are current flow models for transcranial electrical stimulation fit for purpose?
PMID- 28420581
TI - Response variability of different anodal transcranial direct current stimulation
intensities across multiple sessions.
AB - BACKGROUND: It is well known that transcranial direct current stimulation (tDCS)
is capable of modulating corticomotor excitability. However, a source of growing
concern has been the observed inter- and intra-individual variability of tDCS
responses. Recent studies have assessed whether individuals respond in a
predictable manner across repeated sessions of anodal tDCS (atDCS). The findings
of these investigations have been inconsistent, and their methods have some
limitations (i.e. lack of sham condition or testing only one tDCS intensity).
OBJECTIVE: To study inter- and intra-individual variability of atDCS effects at
two different intensities on primary motor cortex (M1) excitability. METHODS:
Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in
three separate conditions (2 mA, 1 mA, sham) each repeated three times separated
by 48 h. Motor evoked potentials were recorded before and after stimulation (up
to 30min). Time of testing was maintained consistent within participants. To
estimate the reliability of tDCS effects across sessions, we calculated the Intra
class Correlation Coefficient (ICC). RESULTS: AtDCS at 2 mA, but not 1 mA,
significantly increased cortical excitability at the group level in all sessions.
The overall ICC revealed fair to high reliability of tDCS effects for multiple
sessions. Given that the distribution of responses showed important variability
in the sham condition, we established a Sham Variability-Based Threshold to
classify responses and to track individual changes across sessions. Using this
threshold an intra-individual consistent response pattern was then observed only
for the 2 mA condition. CONCLUSION: 2 mA anodal tDCS results in consistent intra-
and inter-individual increases of M1 excitability.
PMID- 28420583
TI - Diabetes medication persistence, different medications have different persistence
rates.
AB - AIM: To assess the persistence of diabetic patients to oral medications. METHODS:
The study included all type 2 diabetic patients over 40 years, members of one
District of Clalit Health Services Israel, who were diagnosed with diabetes
mellitus before 2008 and who filled at least one prescription per year during
2008-2010, for the following medications: metformin, glibenclamide, acarbose,
statins, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II
receptor antagonists (ARBs). Purchase of at least 9 monthly prescriptions during
2009 was considered "good medication persistence". We compared HbA1c and LDL
levels, according to medication persistence, for each medication; and cross
persistence rates between medications. RESULTS: 21,357 patients were included.
Average age was 67.0+/-11.0years, 48.9% were men, and 35.8% were from low SES.
Good medication persistence rates for ARBs were 78.8%, ACEI 69.0%, statins 66.6%,
acarbose 67.8%, metformin 58.6%, and glibenclamide 55.3%. Good persistence to any
of the medications tested was associated with a higher rate of good persistence
to other medications. Patients who took more medications had better persistence
rates. CONCLUSIONS: Different oral medications used by diabetic patients have
different persistence rates. Good persistence for any one medication is an
indicator of good persistence to other medications. Investment in enhancing
medication persistence in persons with diabetes may improve persistence to other
medications, as well as improve glycemic control.
PMID- 28420584
TI - Neuroendocrine Carcinoma of the Breast With Endobronchial Metastases and Syndrome
of Inappropriate Antidiuretic Hormone Secretion.
PMID- 28420585
TI - Adjuvant Chemotherapy Is Associated With Improved Overall Survival in Locally
Advanced Rectal Cancer After Achievement of a Pathologic Complete Response to
Chemoradiation.
AB - BACKGROUND: In locally advanced rectal adenocarcinoma, 15% to 20% of patients
treated with neoadjuvant chemoradiation (nCRT) achieve a pathologic complete
response (pCR). The benefit of adjuvant chemotherapy is controversial in rectal
cancer. Our objective was to evaluate the effect of clinical risk factors and
adjuvant chemotherapy usage on the outcomes of the pCR patient population.
PATIENTS AND METHODS: We performed a retrospective study using the National
Cancer Data Base from 2006 to 2013. The primary outcome was overall survival
(OS). The association between OS and patient characteristics (demographics, tumor
variables, and treatment) was examined using multivariable Cox regression
modelling. RESULTS: A total of 2891 patients were identified who had achieved a
pCR. Of these 2891 patients, 2102 received nCRT and 789 received nCRT followed by
adjuvant chemotherapy. The median follow-up duration was 43.2 months. The factors
significantly associated with OS included age (P < .001), gender (P = .011),
Charlson-Deyo comorbidity score (P < .001), grade (P = .029), clinical T stage (P
= .030), carcinoembryonic antigen negativity (P = .002), and receipt of adjuvant
chemotherapy (P < .001). Nodal status was not significantly associated with
survival. The 5-year OS rate was 94% in the nCRT plus adjuvant group compared
with 84% in the nCRT-alone group. Adjuvant chemotherapy was more likely to be
given to younger patients (aged < 60 years), higher grade, lower Charlson-Deyo
comorbidity score, elevated carcinoembryonic antigen level, higher clinical T
stage, and higher clinical N stage. CONCLUSION: Our findings showed a significant
improvement in OS for patients who received nCRT plus adjuvant chemotherapy
compared with those who received nCRT alone. The nCRT plus adjuvant patients were
more likely to be younger, have a lower comorbidity score, have clinical >= T3
disease, and have clinical node-positive disease. Thus, a selection bias could
have been present. Nonetheless, even in the setting of already excellent
outcomes, for patients with locally advanced rectal adenocarcinoma who achieve a
pCR, the additional benefit of adjuvant chemotherapy should be weighed against
the potential for toxicity.
PMID- 28420586
TI - Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass.
AB - The anatomic and physiologic changes in the gastrointestinal (GI) tract after
bariatric surgery may significantly affect the pharmacokinetics of medications
taken by the patients for various reasons. Unfortunately, there is little
information regarding changes in drug absorption after bariatric surgeries,
limiting the ability of medical professionals to produce clear recommendations on
what changes should be made to the formulations and dosing regimens of drugs
after bariatric surgery. In this article, we report and analyze a case of 52-year
old male patient with morbid obesity and attention-deficit/hyperactivity disorder
(ADHD) who experienced lack of methylphenidate efficacy after Roux en-Y gastric
bypass (RYGB), which was eventually resolved by using the transdermal patch
instead of an oral product. Interestingly, in the same patient, a prior gastric
band had no effect on the drug's efficacy. Especially in light of a recent case
report of methylphenidate toxicity after RYGB, these 2 cases suggest that
bariatric surgeries may alter the absorption of orally administered
methylphenidate in an unpredictable manner; hence, it is prudent to closely
monitor the therapeutic/toxic effects of methylphenidate after bariatric surgery,
and to be aware of nonoral treatment options of this medication.
PMID- 28420587
TI - Should recent smoking be a contraindication for sleeve gastrectomy?
AB - BACKGROUND: One of the ultimate goals of bariatric and metabolic surgery is to
decrease cardiovascular morbidity and mortality. Obese individuals who smoke
tobacco are at an increased risk of cardiovascular events and may benefit the
most by positive effects of bariatric surgery on cardiometabolic risk factors.
The safety profile of sleeve gastrectomy in patients who smoke has not yet been
characterized. OBJECTIVES: To investigate the independent effect of smoking on
early postoperative morbidity and mortality of laparoscopic sleeve gastrectomy.
SETTING: American College of Surgeons National Surgical Quality Improvement
Program (NSQIP) database. METHODS: All patients undergoing primary laparoscopic
sleeve gastrectomy from 2010 to 2014 were identified within the NSQIP database.
Thirty-day postoperative outcomes for smokers, defined as patients who smoked
within the year before surgery, were compared with nonsmokers. RESULTS: A total
of 33,714 people underwent sleeve gastrectomy; 30,418 (90.2%) patients were
nonsmokers, whereas 3296 (9.8%) patients smoked within a year before surgery.
Among the 17 examined individual adverse events, patients who smoked were more
likely to experience an unplanned reintubation (odds ratio [OR] = 1.88, 95%
confidence interval [CI]: 1.01-3.50). Patients in the smoking group were
significantly more likely to experience a composite morbidity event (4.3% versus
3.7%, P = .04), serious morbidity event (.9% versus .6%, P = .003), and 30-day
mortality (0.2% versus .1%, P = .0004). The length of hospital stay, unplanned
readmission, and readmission rates were comparable between the 2 groups. These
differences in the composite morbidity event, serious morbidity event, and
mortality persisted even when those patients with chronic obstructive pulmonary
disease, used as a surrogate for end-stage pulmonary effects of smoking, were
excluded from the analysis. CONCLUSION: Sleeve gastrectomy is a well-tolerated
procedure in nonsmokers and smokers. However, patients who have smoked within a
year before sleeve gastrectomy are at an increased, albeit still very low, risk
for 30-day morbidity and mortality compared with nonsmokers. Additional studies
are needed to determine if long-term improvement in co-morbidities can offset
this initial modest increased perioperative risk.
PMID- 28420588
TI - Comparison of an electronic versus traditional food diary for assessing dietary
intake-A validation study.
AB - BACKGROUND: Paper-based estimated food diaries are often used in research to
collect dietary data, despite this method being burdensome for both participants
and researchers. Such food diaries are often time consuming, labour intensive,
and rely on participant literacy and therefore may lead to greater rates of under
reporting. METHODS: This study assessed the validity of the 'Boden Food Plate', a
novel web-based electronic application, compared to a paper-based three-day
estimated food diary. Participants were also asked to rate their satisfaction
with the new electronic diary. Sixty-seven participants with overweight or
obesity completed both the electronic and paper-based diaries at two different
time-points. RESULTS: Baseline BMI of participants (mean+/-standard deviation
(SD)) was 30.4+/-2.9kg/m2, body weight was 87.6+/-13.4kg, and age was 42.3+/
7.7years. Fifty four percent (n=41) of the cohort were female. Bland Altman plots
for total energy, and percentage of total energy intake from fat, carbohydrate,
and protein, indicated wide limits of agreement between the two methods of
dietary data collection, and in some analyses there were a few cases that did not
lie within the 95% confidence intervals. Approximately 70% of participants rated
the electronic food diary as easier to use and more fun when compared to the
traditional paper-based estimated food diary. CONCLUSION: Innovative and visual
dietary collection applications such as the 'Boden Food Plate' provide an
enjoyable and interactive means of measuring nutritional intake in a time
efficient manner. Further validation studies incorporating micronutrient analysis
and to improve the applications validity are warranted.
PMID- 28420589
TI - Associations between language acculturation, age of immigration, and obesity in
the Mexican American Mano A Mano cohort.
AB - INTRODUCTION: As Mexican immigrants to the U.S. become acculturated, they face
worsening health outcomes such as obesity. The role of language acculturation in
the development of obesity has not been thoroughly examined. METHODS: To examine
associations between language acculturation and obesity, data were drawn from the
Mexican-American Mano A Mano cohort study. Participants aged 20 years and over
(n=18,298) completed baseline questionnaires on socio-demographic and behavioural
factors, including physical activity and sitting time. The Bi-dimensional
Acculturation Scale for Hispanics assessed language acculturation. Multivariate
adjusted logistic regression was conducted to investigate associations between
language acculturation, immigration age, and obesity, and whether sitting time
and physical activity mediated these associations. RESULTS: Individuals with
obesity were more linguistically acculturated than individuals who were normal
weight or overweight (P<0.001); however, this relationship differed by gender and
nativity. Among Mexico-born women, language acculturation score was inversely
related to BMI (P<0.001). Language acculturation was associated with higher risk
of obesity (OR=1.35, 95% CI: 1.12-1.62) in U.S.-born participants and lower risk
in Mexico-born participants (OR=0.90, 95%CI=0.81-1.00). For Mexico-born
participants, arrival in the U.S. as an adult (>=20years old) was associated with
a reduced obesity risk (OR=0.74, 95% CI: 0.67-0.80). Sitting time mediated the
association between language acculturation and obesity. CONCLUSIONS: Language
acculturation may influence obesity development among the U.S.-born Mexican
Americans in this cohort, but not their Mexico-born counterparts. Sitting time
could be targeted in obesity prevention efforts in this population.
PMID- 28420590
TI - Volume and dimensions of angiographically normal coronary arteries assessed by
multidetector computed tomography.
AB - BACKGROUND: The objective of this study was to determine normal values for
coronary artery volume (CAV) and individual vasculature and segment dimensions.
METHODS: We examined 200 healthy volunteers with an Agatston score of 0 and a
normal, high quality coronary CTA. Using 320 slice multidetector row CT and
designated vessel tracing software with border detection algorithm, the main
coronary arteries and branches were delineated and total and segmental dimensions
calculated. RESULTS: 2931 segments (98.9%) could be adequately delineated. Of the
173 subjects with adequate coronary delineations, 140 subjects (81%) received
nitroglycerin (NTG) prior to the scan. CAV was 4.33 ml (95% CI: 2.27-6.39) in
subjects with NTG and 2.55 ml (95% CI: 0.34-4.76) in subjects without NTG (p <
0.0001). Left ventricular mass (LVM) was strongly correlated with CAV (p <
0.0001) independently of body surface area and gender, whereas gender was not
independently correlated with CAV. From right, balanced to left coronary
dominance, the left anterior descending artery vasculature mean contribution to
CAV increased slightly (37%, 40% and 43%, p = 0.002), and the mean contributions
of right coronary artery (RCA) and left circumflex artery (LCX) vasculature was
inversely related - from right, balanced to left 46%, 32% and 16% for RCA (p <
0.0001); and 16%, 27% and 38% for LCX (p < 0.0001). CONCLUSION: Normal values for
coronary artery volume as assessed by coronary CTA are reported. They strongly
correlate with NTG administration and left ventricular mass. The respective
contribution of the left and right coronary vascularture is influenced by
coronary dominance.
PMID- 28420591
TI - SCCT and CTA - The future is now.
PMID- 28420592
TI - Association between perceived discrimination and healthcare-seeking behavior in
people with a disability.
AB - BACKGROUND: Experiences of discrimination lead people from vulnerable groups to
avoid medical healthcare. It is yet to be known if such experiences affect people
with disabilities (PWD) in the same manner. OBJECTIVES: To determine the
association between perceived discrimination and healthcare-seeking behavior in
people with disabilities and to explore differences of this association across
disability types. METHODS: We performed a cross-sectional study with data from a
national survey of people with disabilities. Perceived discrimination and care
seeking behavior were measured as self-reports from the survey. Dependence for
daily life activities, possession of health insurance, and other disability
related variables were included and considered as confounders. We used Poisson
regression models and techniques for multistage sampling in the analyses. A
stratified analysis was used to explore effects of discrimination across types of
disability. RESULTS: Most of PWD were 65 years or older (67.1%). Prevalence of
healthcare seeking was 78.8% in those who perceived discrimination, and 86.1% in
those who did not. After adjusting for potential confounders, the probability of
not seeking care was higher in people who reported perceived discrimination
(adjusted PR = 1.15; 95%CI: 1.04-1.28). In a stratified analysis, significant
effects of discrimination were found in people with communication disability
(adjusted PR = 1.34, 95%CI: 1.07-1.67) and with physical disability (adjusted PR
= 1.17, 95%CI: 1.03-1.34). CONCLUSIONS: People with disabilities who perceive
discrimination are less likely to seek healthcare. This association was higher
for people with communication and physical disabilities. These results provide
evidence to institutions who attempt to tackle discrimination.
PMID- 28420593
TI - Sexual health in the community: Services for people with intellectual and
developmental disabilities.
AB - BACKGROUND: Sexuality is a central dimension of overall health and well-being.
People with intellectual and developmental disabilities (IDD) continue to
experience disparities in healthcare, particularly regarding access to sexual
health related services. Medicaid Home and Community-Based Services (HCBS)
waivers are ideally situated to provide sexual and reproductive healthcare in
accessible settings. OBJECTIVE: This preliminary study analyzed national Medicaid
HCBS waivers to determine how they provide sexuality services for people with
IDD. METHODS: 111 FY 2015 HCBS 1915(c) waivers for people with IDD from 46 states
and the District of Columbia were analyzed to determine which waivers were
providing services related to sexuality. Expenditure and utilization data were
analyzed to determine service allotment. RESULTS: Currently, less than 12% of
waivers include any kind of sexuality services, and those services provided are
predominantly reactive, rather than proactive. Reactive services focused on
interrupting sexually inappropriate behaviors through assessments and plans,
intervention and therapy, and supervision. Meanwhile, proactive services promoted
the healthy sexuality of people with IDD by providing sexuality education related
to sexuality awareness, reproduction, and victimization avoidance. CONCLUSIONS:
The limited availability of Medicaid HCBS sexuality service provision not only
hints at a lack of understanding of sexuality for people with IDD, but also
presents an opportunity to perform increased evaluations on current service
offerings in order to justify future expanded offerings in other states.
PMID- 28420594
TI - Population data of 18 autosomal STR loci in the Chinese Han population from
Heilongjiang Province, Northeast China.
PMID- 28420595
TI - Using an array of implementation strategies to improve success rates of
pharmacist-initiated medication therapy management services in community
pharmacies.
AB - BACKGROUND: With the introduction of the Centers for Medicare and Medicaid
Services Stars Measure program has come a greater expectation of Medication
Therapy Management (MTM) services from community pharmacies. To meet the growing
demand of these services, pharmacies have sought out various methods of engaging
pharmacists to provide MTM. Barriers for completing MTM include inadequate time
to complete the services, insufficient staffing, lack of sufficient compensation,
billing difficulty, lack of interest among patients (including refusing MTM
services when offered), inadequate training/experience, and lack of support from
management. OBJECTIVE: To evaluate the impact of a financial incentive alone
versus the incentive plus a package of individualized implementation strategies
on the success rate of MTM services. METHODS: To increase MTM completion rates,
The Kroger Company implemented a financial incentive for pharmacists in one of
its market services areas. The following year the incentive was continued and an
array of training and support strategies were implemented. The numbers of MTM
claims and success rates for 2013 (no intervention), 2014 (financial incentive
alone), and 2015 (incentive plus required training and ongoing support) were
compared. RESULTS: A total of 7038 claims were extracted from 2013 to 2015. The
number of completed claims had increased from 1385 in 2013 to 3265 in 2015. The
total MTM success rates rose significantly from 42.9% in 2013 to 49.0% in 2014 (p
= 0.001) and to 64.0% in 2015 (p < 0.001). CONCLUSIONS: A financial incentive
plus a package of individualized implementation strategies increases success
rates of MTM services compared to a financial incentive alone.
PMID- 28420596
TI - The behaviors and experiences of the community pharmacy team on the provision of
multi-compartment compliance aids.
AB - BACKGROUND: Multi-compartment compliance aids (MCAs) are repackaging systems for
solid dosage form medicines. Acknowledging the lack of evidence that MCAs improve
adherence or clinical outcomes, the Royal Pharmaceutical Society has expressed
concern that MCAs have 'become regarded as a panacea for medicines use'.
OBJECTIVES: To determine the behaviors and experiences of the community pharmacy
team around MCA provision. METHODS: A cross-sectional survey was conducted in 26
community pharmacies in the north east of Scotland. Survey items were grouped
into: current activities in the provision of MCAs; potential influences on these
activities; reports of patient experiences; and demographics. Data were analysed
using descriptive and inferential statistics, and content analysis of responses
to open questions. Principal component analysis (PCA) was performed on the items
of potential influences on activities. RESULTS: Data were collected from 136
community team members (median 4, range1-10 per pharmacy; 32.3% pharmacists). All
were involved in some aspect of MCA provision and within the same pharmacy,
several different staff positions were commonly involved in the same activity.
PCA gave seven components; the lowest scores were obtained for the component of
'others expecting me to provide MCAs'. Participants agreed that GPs, patients and
their families, and carers expected them to provide MCAs. Positive experiences of
MCA provision were in themes of promoting patient adherence, reducing patient
stress and enhancing patient monitoring. Further negative experiences were in of
lack of shared patient decision making, worsening adherence and generation of
medicines waste, and dealing with changing medicines. MCAs were not always
considered to be the most appropriate solution. CONCLUSION: While community
pharmacy teams value MCAs, there may be issues around staff assignment to
particular roles, expectations from others and reports of negative patient
experiences. A systematic approach to MCA provision and monitoring involving the
multidisciplinary health and social care team is warranted.
PMID- 28420597
TI - Discrepant lesion size estimated on T1- and fat-suppressed T2-weighted MRI:
diagnostic value for differentiation between inflammatory pseudotumor and
carcinoma of the nasopharynx.
AB - PURPOSE: Nasopharyngeal inflammatory pseudotumor (NIPT) is hard to differentiate
from infiltrating nasopharyngeal carcinoma (NPC) on conventional magnetic
resonance imaging (MRI). The purpose of this study is to determine whether
discrepant lesion sizes estimated on T1- and fat-suppressed T2-weighted images
can help distinguish between NIPT and NPC. METHODS: We retrospectively reviewed
MRI data of histologically proven 14 NIPTs and 18 infiltrating NPCs. We measured
the area of the lesion on contrast-enhanced T1-weighted, unenhanced T1-weighted,
and fat-suppressed T2-weighted images by placing the largest possible polygonal
region-of-interest within the lesion at the same level. Using lesion size
measured on contrast-enhanced T1-weighted image as the reference, we calculated
and compared area ratio of T1 (ART1) and area ratio of T2 (ART2) between NIPTs
and NPCs. For validation, we also undertook a double-blinded study by two
reviewers and assessed the diagnostic performance and interobserver agreement.
RESULTS: For NIPTs, ART2 (median, 0.48; range, 0.18-0.97) was statistically
significantly less than ART1 (median, 1.01; range, 0.80-1.99), while these values
were not significantly different for NPCs. The interobserver agreement in
differentiating between NIPT and NPC was good, with a sensitivity of 93% and a
specificity of 83%-94%. CONCLUSION: In contrast to NPCs, NIPTs appear smaller on
fat-suppressed T2-weighted images than on T1-weighted images. This discrepancy in
the lesion size estimated on T1-weighted and fat-suppressed T2-weighted images
may provide a simple and consistent way to differentiate between NIPTs and NPCs
on conventional MRI.
PMID- 28420598
TI - 1.5 T augmented reality navigated interventional MRI: paravertebral sympathetic
plexus injections.
AB - PURPOSE: The high contrast resolution and absent ionizing radiation of
interventional magnetic resonance imaging (MRI) can be advantageous for
paravertebral sympathetic nerve plexus injections. We assessed the feasibility
and technical performance of MRI-guided paravertebral sympathetic injections
utilizing augmented reality navigation and 1.5 T MRI scanner. METHODS: A total of
23 bilateral injections of the thoracic (8/23, 35%), lumbar (8/23, 35%), and
hypogastric (7/23, 30%) paravertebral sympathetic plexus were prospectively
planned in twelve human cadavers using a 1.5 Tesla (T) MRI scanner and augmented
reality navigation system. MRI-conditional needles were used. Gadolinium-DTPA
enhanced saline was injected. Outcome variables included the number of control
magnetic resonance images, target error of the needle tip, punctures of critical
nontarget structures, distribution of the injected fluid, and procedure length.
RESULTS: Augmented-reality navigated MRI guidance at 1.5 T provided detailed
anatomical visualization for successful targeting of the paravertebral space,
needle placement, and perineural paravertebral injections in 46 of 46 targets
(100%). A mean of 2 images (range, 1-5 images) were required to control needle
placement. Changes of the needle trajectory occurred in 9 of 46 targets (20%) and
changes of needle advancement occurred in 6 of 46 targets (13%), which were
statistically not related to spinal regions (P = 0.728 and P = 0.86,
respectively) and cadaver sizes (P = 0.893 and P = 0.859, respectively). The mean
error of the needle tip was 3.9+/-1.7 mm. There were no punctures of critical
nontarget structures. The mean procedure length was 33+/-12 min. CONCLUSION: 1.5
T augmented reality-navigated interventional MRI can provide accurate imaging
guidance for perineural injections of the thoracic, lumbar, and hypogastric
sympathetic plexus.
PMID- 28420599
TI - Use of Machine Learning Classifiers and Sensor Data to Detect Neurological
Deficit in Stroke Patients.
AB - BACKGROUND: The pronator drift test (PDT), a neurological examination, is widely
used in clinics to measure motor weakness of stroke patients. OBJECTIVE: The aim
of this study was to develop a PDT tool with machine learning classifiers to
detect stroke symptoms based on quantification of proximal arm weakness using
inertial sensors and signal processing. METHODS: We extracted features of drift
and pronation from accelerometer signals of wearable devices on the inner wrists
of 16 stroke patients and 10 healthy controls. Signal processing and feature
selection approach were applied to discriminate PDT features used to classify
stroke patients. A series of machine learning techniques, namely support vector
machine (SVM), radial basis function network (RBFN), and random forest (RF), were
implemented to discriminate stroke patients from controls with leave-one-out
cross-validation. RESULTS: Signal processing by the PDT tool extracted a total of
12 PDT features from sensors. Feature selection abstracted the major attributes
from the 12 PDT features to elucidate the dominant characteristics of proximal
weakness of stroke patients using machine learning classification. Our proposed
PDT classifiers had an area under the receiver operating characteristic curve
(AUC) of .806 (SVM), .769 (RBFN), and .900 (RF) without feature selection, and
feature selection improves the AUCs to .913 (SVM), .956 (RBFN), and .975 (RF),
representing an average performance enhancement of 15.3%. CONCLUSIONS: Sensors
and machine learning methods can reliably detect stroke signs and quantify
proximal arm weakness. Our proposed solution will facilitate pervasive monitoring
of stroke patients.
PMID- 28420600
TI - Increasing Fruit and Vegetable Consumption Through a Healthy Eating Blog: A
Feasibility Study.
AB - BACKGROUND: Despite efforts made by public health organizations to improve
consumption of fruits and vegetables, populations in developed countries usually
eat less than the minimum recommended. Social media, such as blogs, represent a
unique opportunity for improving knowledge translation in health care because
they facilitate interactive communication between the public and health
professionals. However, no studies have yet evaluated the effect of blogs to
promote dietary behavior changes. OBJECTIVE: Our study aims to conduct a
preliminary assessment before undertaking a full randomized controlled trial
(RCT) of the feasibility of using an evidence-based healthy eating blog promoting
the consumption of fruits and vegetables among adult women. METHODS: A total of
80 women aged 18 years and older (mean 42, SD 13 years) eating less than five
servings per day of fruit and vegetables (mean 2.75, SD 1.84 servings) were
recruited. Participants were randomized to the healthy eating blog group (n=40),
which included a weekly blog post over a 6-month period, or to a control group
(n=40) that had no exposure to the healthy eating blog. Blog posts were written
by a registered dietitian and focused on the improvement of fruit and vegetable
consumption. We targeted four main determinants of the behavior that were
identified as the best predictors for fruit and vegetable intake by two
systematic reviews: (1) knowledge, (2) attitude, (3) self-efficacy, and (4)
motivation. The intervention was considered feasible if (1) more than 70% of
questionnaires were completed, (2) attendance rate was more than 90% for in
person appointments with the research coordinator, (3) participants accessed at
least 75% of the blog posts, and (4) the attrition rate was less than 25%. Blog
access was assessed by collecting the blog browsing history data for each
participant. RESULTS: During the intervention, 26 posts were published on the
blog. Pre- (baseline) and postintervention (6 months) questionnaires were
completed by mean 97% (SD 3%) of participants. All participants attended their in
person appointments. Women accessed mean 87% (SD 7%) of the posts published
during the intervention. Only 3% (2/80) of participants dropped out of the study.
Between the healthy eating blog and control groups, a difference of 1.0 servings
of fruits and vegetables (P<.001) indicated moderate effects of the intervention
(Cohen d=0.54). CONCLUSIONS: These results suggest that an intervention using a
healthy eating blog meets preestablished feasibility criteria. A larger-scale RCT
using the same methodology will be conducted to assess the impact of a healthy
eating blog on the dietary habits of women.
PMID- 28420601
TI - What Older People Like to Play: Genre Preferences and Acceptance of Casual Games.
AB - BACKGROUND: In recent computerized cognitive training studies, video games have
emerged as a promising tool that can benefit cognitive function and well-being.
Whereas most video game training studies have used first-person shooter (FPS)
action video games, subsequent studies found that older adults dislike this type
of game and generally prefer casual video games (CVGs), which are a subtype of
video games that are easy to learn and use simple rules and interfaces. Like
other video games, CVGs are organized into genres (eg, puzzle games) based on the
rule-directed interaction with the game. Importantly, game genre not only
influences the ease of interaction and cognitive abilities CVGs demand, but also
affects whether older adults are willing to play any particular genre. To date,
studies looking at how different CVG genres resonate with older adults are
lacking. OBJECTIVE: The aim of this study was to investigate how much older
adults enjoy different CVG genres and how favorably their CVG characteristics are
rated. METHODS: A total of 16 healthy adults aged 65 years and above playtested 7
CVGs from 4 genres: casual action, puzzle, simulation, and strategy video games.
Thereafter, they rated casual game preference and acceptance of casual game
characteristics using 4 scales from the Core Elements of the Gaming Experience
Questionnaire (CEGEQ). For this, participants rated how much they liked the game
(enjoyment), understood the rules of the game (game-play), learned to manipulate
the game (control), and make the game their own (ownership). RESULTS: Overall,
enjoyment and acceptance of casual game characteristics was high and
significantly above the midpoint of the rating scale for all CVG genres. Mixed
model analyses revealed that ratings of enjoyment and casual game characteristics
were significantly influenced by CVG genre. Participants' mean enjoyment of
casual puzzle games (mean 0.95 out of 1.00) was significantly higher than that
for casual simulation games (mean 0.75 and 0.73). For casual game
characteristics, casual puzzle and simulation games were given significantly
higher game-play ratings than casual action games. Similarly, participants'
control ratings for casual puzzle games were significantly higher than that for
casual action and simulation games. Finally, ownership was rated significantly
higher for casual puzzle and strategy games than for casual action games.
CONCLUSIONS: The findings of this study show that CVGs have characteristics that
are suitable and enjoyable for older adults. In addition, genre was found to
influence enjoyment and ratings of CVG characteristics, indicating that puzzle
games are particularly easy to understand, learn, and play, and are enjoyable.
Future studies should continue exploring the potential of CVG interventions for
older adults in improving cognitive function, everyday functioning, and well
being. We see particular potential for CVGs in people suffering from cognitive
impairment due to dementia or brain injury.
PMID- 28420602
TI - The Fitbit One Physical Activity Tracker in Men With Prostate Cancer: Validation
Study.
AB - BACKGROUND: Physical activity after cancer diagnosis improves quality of life and
may lengthen survival. However, objective data in cancer survivors are limited
and no physical activity tracker has been validated for use in this population.
OBJECTIVE: The aim of this study was to validate the Fitbit One's measures of
physical activity over 7 days in free-living men with localized prostate cancer.
METHODS: We validated the Fitbit One against the gold-standard ActiGraph GT3X+
accelerometer in 22 prostate cancer survivors under free-living conditions for 7
days. We also compared these devices with the HJ-322U Tri-axis USB Omron
pedometer and a physical activity diary. We used descriptive statistics (eg,
mean, standard deviation, median, interquartile range) and boxplots to examine
the distribution of average daily light, moderate, and vigorous physical activity
and steps measured by each device and the diary. We used Pearson and Spearman
rank correlation coefficients to compare measures of physical activity and steps
between the devices and the diary. RESULTS: On average, the men wore the devices
for 5.8 days. The mean (SD) moderate-to-vigorous physical activity (MVPA;
minutes/day) measured was 100 (48) via Fitbit, 51 (29) via ActiGraph, and 110
(78) via diary. The mean (SD) steps/day was 8724 (3535) via Fitbit, 8024 (3231)
via ActiGraph, and 6399 (3476) via pedometer. Activity measures were well
correlated between the Fitbit and ActiGraph: 0.85 for MPVA and 0.94 for steps
(all P<.001). The Fitbit's step measurements were well correlated with the
pedometer (0.67, P=.001), and the Fitbit's measure of MVPA was well correlated
with self-reported activity in the diary (0.84; P<.001). CONCLUSIONS: Among
prostate cancer survivors, the Fitbit One's activity and step measurements were
well correlated with the ActiGraph GT3X+ and Omron pedometer. However, the Fitbit
One measured two times more MVPA on average compared with the ActiGraph.
PMID- 28420603
TI - The Coags Uncomplicated App: Fulfilling Educational Gaps Around Diagnosis and
Laboratory Testing of Coagulation Disorders.
AB - BACKGROUND: Patients with coagulation disorders may present to a variety of
physician specialties; however, accurate and efficient diagnosis can be
challenging for physicians not specialized in hematology, due to identified gaps
in knowledge around appropriate laboratory assays and interpretation of test
results. Coags Uncomplicated was developed to fill this unmet educational need by
increasing practical knowledge of coagulation disorders among nonexpert
physicians and other health care professionals (HCPs) in a point-of-care (POC)
setting. OBJECTIVE: The aim of this study was to assess patterns of use of the
mobile app Coags Uncomplicated, a tool designed to support education regarding
accurate and efficient diagnosis of bleeding disorders. METHODS: App metrics were
obtained by tracking registered user data. Additionally, a survey was distributed
to registered users, to assess circumstances and frequency of use. RESULTS: The
most common specialties of 7596 registered US users were hematology-oncology
(n=1534, 20.19%), hematology (n=1014, 13.35%), and emergency medicine (n=1222,
16.09%); most identified as physicians (n=4082, 53.74%). Specialties accounting
for the greatest numbers of screen views were hematology-oncology (99,390 views),
hematology (47,808 views), emergency medicine (23,121 views), and internal
medicine (22,586 views). The most common diagnostic endpoints reached were
disseminated intravascular coagulation (DIC; 2713 times), liver disease effect
(2108 times), and vitamin K deficiency (1584 times). Of 3424 users asked to take
the survey, 262 responded (7.65%); most were physicians in direct clinical care
(71%) and specialized in hematology-oncology (39%) or emergency medicine (21%).
Most frequent use was reported by hematologists (69%, >=6 times) and
hematologists-oncologists (38%, >=6 times). Most physicians (89.2%) reported
using the app for patient-case-related education around appropriate use of
laboratory tests in diagnostic evaluation. Physicians rated Lab Value Analyzer
(mean 4.43) and Lab Test Algorithm (mean 4.46) tools highly on a 5-point "how
helpful" scale and were likely to recommend the app to colleagues. CONCLUSIONS:
App use among physicians and other HCPs is consistent with value as a POC
educational tool, which may facilitate differential diagnoses and appropriate
early consultation with hematologists.
PMID- 28420604
TI - A Digital Tool to Promote Alcohol and Drug Use Screening, Brief Intervention, and
Referral to Treatment Skill Translation: A Mobile App Development and Randomized
Controlled Trial Protocol.
AB - BACKGROUND: Translation of knowledge and skills from classroom settings to
clinical practice is a major challenge in healthcare training, especially for
behavioral interventions. For example, screening, brief intervention, and
referral to treatment (SBIRT) is a highly-promoted approach to identifying and
treating individuals at risk for alcohol or drug problems, yet effective, routine
use of SBIRT has lagged. OBJECTIVE: The objective of this paper is to describe
the development, pilot testing, and trial protocol of a mobile app based on the
theory of planned behavior (TPB) to promote SBIRT skill translation and
application. METHODS: Intended for use after classroom training occurs, the
mobile app has three primary functions designed to increase behavioral intent to
deliver SBIRT: (1) review skills (ie, address knowledge and beliefs about SBIRT),
(2) apply skills with patients (ie, build confidence and perceived behavioral
control), and (3) report performance data (ie, increase accountability and social
norms and/or influence). The app includes depression and anxiety screening tools
due to high comorbidity with substance use. A randomized controlled trial (RCT)
is in progress among health and social service learners (N=200) recruited from 3
universities and 6 different training programs in nursing, social work, internal
medicine, psychiatry, and psychology. Participants are randomized to SBIRT
classroom instruction alone or classroom instruction plus app access prior to
beginning their field placement rotations. TPB-based data are collected via
Qualtrics or via the mobile app pre-post and SBIRT utilization, weekly for 10
weeks. Key outcomes include the frequency of and self-reported confidence in
delivery of SBIRT. RESULTS: Beta testing with advanced practice nursing students
(N=22) indicated that the app and its associated assessment tools were acceptable
and useful. The system usability scale (SUS) mean was 65.8 (n=19), which
indicated that the SBIRT app was acceptable but could benefit from improvement.
Indeed, modifications were implemented prior to starting the trial. Enrollment of
trial participants began in September 2016. Results are expected by December
2017. CONCLUSIONS: This report describes the process of TPB-based app development
and testing, and the protocol for a RCT to determine the effectiveness of the app
in enhancing skill translation. If effective, this approach could improve SBIRT
implementation, fidelity, and clinical outcomes.
PMID- 28420605
TI - Scalable Passive Sleep Monitoring Using Mobile Phones: Opportunities and
Obstacles.
AB - BACKGROUND: Sleep is a critical aspect of people's well-being and as such
assessing sleep is an important indicator of a person's health. Traditional
methods of sleep assessment are either time- and resource-intensive or suffer
from self-reporting biases. Recently, researchers have started to use mobile
phones to passively assess sleep in individuals' daily lives. However, this work
remains in its early stages, having only examined relatively small and
homogeneous populations in carefully controlled contexts. Thus, it remains an
open question as to how well mobile device-based sleep monitoring generalizes to
larger populations in typical use cases. OBJECTIVE: The aim of this study was to
assess the ability of machine learning algorithms to detect the sleep start and
end times for the main sleep period in a 24-h cycle using mobile devices in a
diverse sample. METHODS: We collected mobile phone sensor data as well as daily
self-reported sleep start and end times from 208 individuals (171 females; 37
males), diverse in age (18-66 years; mean 39.3), education, and employment
status, across the United States over 6 weeks. Sensor data consisted of
geographic location, motion, light, sound, and in-phone activities. No specific
instructions were given to the participants regarding phone placement. We used
random forest classifiers to develop both personalized and global predictors of
sleep state from the phone sensor data. RESULTS: Using all available sensor
features, the average accuracy of classifying whether a 10-min segment was
reported as sleep was 88.8%. This is somewhat better than using the time of day
alone, which gives an average accuracy of 86.9%. The accuracy of the model
considerably varied across the participants, ranging from 65.1% to 97.3%. We
found that low accuracy in some participants was due to two main factors: missing
sensor data and misreports. After correcting for these, the average accuracy
increased to 91.8%, corresponding to an average median absolute deviation (MAD)
of 38 min for sleep start time detection and 36 min for sleep end time. These
numbers are close to the range reported by previous research in more controlled
situations. CONCLUSIONS: We find that mobile phones provide adequate sleep
monitoring in typical use cases, and that our methods generalize well to a
broader population than has previously been studied. However, we also observe
several types of data artifacts when collecting data in uncontrolled settings.
Some of these can be resolved through corrections, but others likely impose a
ceiling on the accuracy of sleep prediction for certain subjects. Future research
will need to focus more on the understanding of people's behavior in their
natural settings in order to develop sleep monitoring tools that work reliably in
all cases for all people.
PMID- 28420606
TI - Epigenetic regulation and related diseases during placental development.
AB - The placenta is vital to fetal growth and development, as it bridges the fetus
and the mother. Genome-wide epigenetic regulations (e.g., DNA methylation,
histone modifications, non-coding RNAs) participate in many aspects of placenta
development, including decidua of the uterus, trophoblast cell adhesion and
invasion, angiogenesis and placental imprinted gene expression. Environmental
factors during pregnancy, such as heavy metals, chemical compounds, modern
assisted reproductive technology and the nutrient conditions, may cause abnormal
placental epigenetics. Furthermore, sex differential expression of placental
genes also contributes to epigenetic modifications. As prenatal DNA methylation
analysis can detect abnormal epigenetic modifications, it is a potential
diagnosis tool for early stage diseases and may help disease intervention and
treatment. Here, we review not only regulations of epigenetic modifications
during development of the placenta, but also the influences of environmental
factors. The potential value for diagnosis and treatment is also discussed.
PMID- 28420607
TI - The research progress of farm animal genomics based on sequencing technologies.
AB - Various farm animal breeds have been domesticated and bred for thousands years,
and they provide adequate animal-derived proteins to meet the human nutrition
requirement. Although quantitative genetics was applied in animal breeding, which
launched a technological revolution in the past century, a number of complex
traits remain difficult to be selected based on pedigree derived breeding, due to
complicated animal genetics and development mechanisms. Farm animal's genetic
potential hasn't yet to be fully exploited. The concept and technology from the
Human Genome Project have greatly promoted farm animal genomic researches. It is
possible to fine map the causal variations at the whole genome level and then
exploit their biological functions, thus providing the theoretical basis for
molecular designed breeding. In this review, we summarize the genomics research
progress of main farm animals during the past decade, including pigs, cattle,
yaks, goats, sheep, chickens, ducks and geese. We focus on the reference genome
sequencing and follow-up population-level genomic studies based on high
throughput resequencing technologies, and meanwhile envision the future work of
farm animal genomics.
PMID- 28420608
TI - The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking
and stress response.
AB - Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on
the plasma membrane. PIPs transfer water, CO2 and small uncharged solutes through
the plasma membrane. PIPs have high selectivity to substrates, suggestive of a
central role in maintaining cellular water balance. The expression, activity and
localization of PIPs are regulated at the transcriptional and post-translational
levels, and also affected by environmental factors. Numerous studies indicate
that the expression patterns and localizations of PIPs can change in response to
abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking,
transcriptional and post-translational regulations, and abiotic stress responses.
Moreover, we also discuss the current research trends and future directions on
PIPs.
PMID- 28420609
TI - Molecule mechanism for regulating stomatal development in plants.
AB - Stomata are small adjustable pores on the surface (epidermis) of land plants that
act as a main conduit for gas exchange. They not only play an essential role in
photosynthesis of green plants but also exert an important influence on the
global carbon and water cycle. There are great differences between monocots and
dicots in distribution and morphological structure of the stomata, affecting the
species-specific regulation of stomatal development. In this review, we summarize
the molecular regulation networks associated with stomatal precursor cell fate
determination and the epigenetic mechanisms on regulation of polar cell division.
We also outline the stomatal development processes mediated by crosstalk between
exogenous and intrinsic signals, and propose a model of multilevel regulation of
stomatal development.
PMID- 28420610
TI - The diversity of DNA fragment editing by CRISPR/Cas9 in highly homologous or
repetitive sequences.
AB - In complex genomes, there are a large number of duplicated genes in the coding
regions and many more repetitive sequences in the non-coding regions. Repetitive
sequences can exert great impacts on the heredity and evolution of the organisms,
as well as their genome 3D architecture and transcriptional regulation. The high
homology nature of repetitive sequences renders their editing by CRISPR/Cas9 very
complex. At diploid or polyploid situations, such repetitive sequences could be
edited differently on each chromosome or chromatid. To explore such
possibilities, we had studied the editing of two highly homologous DNA fragments
(L1 and L2), each about 300 bp in size and 11 kb apart on the same chromosome. We
designed a pair of sgRNAs targeting the upstream and downstream of the two DNA
fragments to guide the Cas9 cleavage of the two fragments in the human HepG2
cells. We further established single-cell CRISPR clones for DNA-fragment-edited
cells. A total of 22 CRISPR cell clones were characterized for their DNA fragment
editing patterns. In addition to the deletion of L1/L2 fragments, we had also
identified the deletion of the large internal fragment between L1 and L2
fragments, and the various combinations of inversions and deletions of the three
DNA fragments. Our results have demonstrated the potential issues with important
implications for using CRISPR/Cas9 to edit duplicated genes or repetitive
sequences in diploid or polyploid species or cell lines.
PMID- 28420611
TI - Characterization of the conbercept gene localization in DHFR- amplified CHO cells
using fluorescence in situ hybridization.
AB - Chinese-hamster ovary (CHO) cells are most widely used for mammalian protein
expression. After integration into the CHO genome, the exogenous gene may be lost
in the process of large-scale protein production due to the removal of related
selection pressures. Therefore, it is necessary to test its stability in the
genome. Conbercept is a fusion protein that specifically binds to the various
isoforms of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental
growth factor (PlGF), thereby exerting anti-angiogenic activities. It has been
approved for Phase III clinical trials in the United States. In this study,
fluorescence in situ hybridization (FISH) was used to localize the conbercept
gene in dihydrofolatereductase (DHFR)-amplified CHO cell lines. Metaphase FISH
showed that genomic integration of the conbercept gene was stable after 4 and 19
passages, and manifested three characteristics: first, the gene locates on one
chromosome, rather than a number of chromosomes; second, the gene locates on the
longer chromosomes; third, there are many copies located on the same chromosome.
At the same time, the copy number of the conbercept gene in the CHO genome and
the conbercept protein expression levels are also stable, as verified by qPCR and
ELISA assays, respectively. These experiments demonstrated that the conbercept
gene remained stable in the genome after 19 passages, and could be actively
expressed, which strongly support the mass production and the quality control of
conbercept.
PMID- 28420612
TI - Identification and analysis of ZFPM2 as a target gene of miR-17-92 cluster in
chicken.
AB - The miR-17-92 cluster plays important roles in a variety of physiological and
pathological processes in mammals. Previously, we showed that miR-17-92 cluster
promotes chicken preadipocyte proliferation; however, the mechanism for its
action is unknown. In order to explore the mechanism by which miR-17-92 cluster
promotes chicken preadipocyte proliferation, CCK8 proliferation assay was
performed to determine the effect of ZFPM2 knockdown on chicken preadipocyte
proliferation. The results showed that ZFPM2 knockdown significantly promoted
chicken preadipocyte proliferation (P<0.01). Consistent with the CCK8 results,
the mRNA levels of cell proliferation marker genes, i.e., Cyclin D1, PCNA and
Ki67, were markedly increased in the si-ZFPM2-transfected preadipocytes (P<0.01
or P<0.05). Bioinformatics analysis showed that there were two potential miRNA
binding sites for the four individual members of miR-17-92 cluster in the ZFPM2
3'UTR, one for miR-17-5p and miR-20a and the other for miR-19a and miR-19b. To
test whether ZFPM2 is a target for the miR-17-92 cluster, the ZFPM2 3'UTR
reporter (psi-CHECK2-ZFPM2-3'UTR-WT) and its mutant reporter (psi-CHECK2-ZFPM2
3'UTR-MUT) were constructed. Reporter assays showed that overexpression of miR-17
92 cluster significantly inhibited the luciferase reporter activity of psi-CHECK2
ZFPM2-3'UTR-WT (P<0.01), as compared with control vector (empty pcDNA3.1).
Transfection of miR-17-5p, miR-19a and miR-20a inhibitors increased the reporter
activities of psi-CHECK2-ZFPM2-3'UTR-WT (P<0.01 or P<0.05). In contrast,
transfection of miR-17-5p, miR-19a, and miR-20a inhibitors had no obvious effect
on reporter activity of psi-CHECK2-ZFPM2-3'UTR-MUT. Further qRT-PCR analysis
showed that miR-17-5p, miR-20a and miR-19a inhibitors significantly elevated the
endogenous ZFPM2 mRNA expression (P<0.01 or P<0.05). Cotransfection of either miR
17-5p or miR-19a inhibitor and siZFPM2 showed that both inhibitors tended to
reduce only slightly the promoting effect of siZFPM2 on chicken preadipocyte
proliferation. Taken together, these data demonstrated that ZFPM2 is a target of
miR-17-5p, miR-20a, miR-19a, and miR-19b, and that miR-17-92 cluster promotes
chicken preadipocyte proliferation at least in part by targeting ZFPM2 and
inhibiting its expression.
PMID- 28420613
TI - Genetic analysis and identification of candidate genes for two spotted-leaf
mutants (spl101 and spl102) in rice.
AB - Spotted-leaf mutants form spots in leaves or leaf sheaths under normal condition.
The spotted-leaf phenotypes are similar to hypersensitive reaction of plants
attacked by pathogen. Identification and characterization of the spotted-leaf
mutants are helpful for understanding the mechanisms of resistance to plant
diseases. Here, we identify two spotted-leaf mutants spl101 and spl102 from an
EMS-treated elite japonica cultivar KYJ (Kuanyejing). spl101 and spl102 form
serious spots at the late heading stage. Genetic analyses show that the spotted
leaf phenotypes of both spl101 and spl102 are caused by a single recessive
mutation, respectively. By employing the Mutmap method, we reveal that both
spl101 and spl102 contain mutations in the OsEDR1 gene. The spl101 mutation
occurs in the 5 degrees -splicing site of the 6th intron of OsEDR1, which causes
abnormal recognition of the 6th intron and leads to the frameshift mutation. The
spl102 mutant contains a mutation in the tenth exon of OsEDR1, resulting in an
amino acid change from the phenylalanine (F) to the cysteine (C). OsEDR1 has been
reported to regulate pathogen-resistant reaction, and loss of OsEDR1 function
produces similar phenotypes to those of spl101 and spl102. Here, two newly
identified alleles of OsEDR1 will be benefit for further understanding the
molecular mechanisms of the OsEDR1 gene in disease resistance, and will be
helpful for enriching the rice germplasm resources. In addition, our results also
validate the effectiveness of the Mutmap method in cloning the candidate
mutations.
PMID- 28420614
TI - Applications of genome editing tools in precision medicine research.
AB - The emergence of genome editing tools, such as the clustered regularly
interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system,
has enabled researchers to achieve somatic and germline genomic manipulations in
cell lines and model organisms. Within a couple of years, genome editing is now
being rapidly developed for multiple applications and widely used in biomedical
researches, including creation of disease models with desired genetic mutations,
screening in a high-throughput manner for drug resistance genes, and making
appropriate editions to genes in vivo for disease treatment. All these
applications have been facilitating the development of precision medicine
research. In this review, we describe the use of genome editing technologies for
a variety of research and translational applications in the precision medicine
field. We also highlight some of the existing limitations or challenges as well
as future directions.
PMID- 28420615
TI - The mechanism and clinical significance of long noncoding RNA-mediated gene
expression via nuclear architecture.
AB - Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts
exceeding 200 nucleotides in length. Accumulating evidence achieved by several
sophisticated techniques such as chromatin conformation capture and RNA-seq has
led to new questions concerning correlations between lncRNAs and chromatin
structures. Many studies have revealed that lncRNAs exert great influences on
gene expression through regulating chromatin 3D structures. In addition, lncRNAs
play a crucial role in tumorigenesis and therefore hold great promises in disease
diagnosis and prognosis. Here, we mainly focus on introducing how lncRNAs
regulate gene expression by modulating nuclear architecture and discussing
clinical values of lncRNAs in oncotherapy.
PMID- 28420616
TI - Aberrant RNA splicing as the molecular basis of some pathogenic variants.
AB - Identification and correct classification of disease-associated mutations are
essential for molecular diagnosis and clinical management of many genetic
disorders. Although next-generation sequencing has greatly accelerated the
detection of nucleotide changes, the biological interpretation of most variants
has become a real challenge. Moreover, attention is typically paid to protein
coding changes and the potential impact of exonic variants on RNA splicing is
often ignored. There is increasing evidence showing that disease-causing aberrant
RNA splicing is more widespread than currently appreciated. Here, we review the
major types of the variants involved in RNA splicing and the approaches used to
identify and characterize these variants. We hope to provide a reference for
evaluation of the effects of mutations on diseases.
PMID- 28420617
TI - Application and progress of high-throughput sequencing technologies in the
research of hereditary hearing loss.
AB - Hearing loss (HL) is the most common birth defect. Elucidating the genetic basis
of hereditary deafness can not only assist diagnosis, provide the basis for
genetic counseling and the prevention of deafness, but also bring a deeper
understanding of the disease pathogenesis. In the genomic era, high-throughput
sequencing technologies, represented by whole genome sequencing (WGS), whole
exome sequencing (WES) or target region sequencing, have been widely used in the
studies of hereditary HL. Here, we summarize the application and progress of WES
and target region sequencing in the research of causative genes and clinical
molecular diagnosis of hereditary HL, hoping to be helpful for the development
and improvement of clinical genetic diagnosis of deafness in China.
PMID- 28420618
TI - Research progress on liquid biopsy in oncology and its clinical applications.
AB - Liquid biopsy is an emerging and promising detection tool for cancer, with the
benefit of being non-invasive and convenient. It analyzes tumor-derived
information in the blood or other body fluids including circulating tumour cells
(CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion
of liquid biopsy research contents and the development of capture and detection
technologies, liquid biopsy is increasingly utilized in clinical applications,
promoting the development of tumor precision medicine. Here, we mainly focus on
reviewing the objects and technologies about liquid biopsy, as well as its
applications, development and challenges in clinical practices.
PMID- 28420619
TI - Analysis of variants in upstream open reading frames of human globin-related
genes.
AB - beta-thalassemia is an autosomal recessive monogenic disease that is caused by
defects in the production of beta-like globin chains. Activation of gamma-globin
gene and the increase in fetal hemoglobin expression have been demonstrated as
one of the most important factors to ameliorate the clinical outcome of beta
thalassemia patients. In this study, 202 genes or miRNAs associated with human
hemoglobin gene expression from 1802 beta-thalassemia patients were analyzed with
target capture and next generation sequencing strategies in terms of functional
variants that might affect hemoglobin gene expression. The subsequent
bioinformatics analysis included assessments of sequence quality, the variants
within the target regions and the 5'UTR with potential effects on upstream open
reading frames (uORFs). Among the 41 variants in 5'UTR potentially affecting the
uORFs identified in the study, two variants (chr19: 41859418 G > A and
chr1:153606541 C > T) were experimentally validated with dual-luciferase assays
to be capable of significantly down-regulating the expression of TGFB1 and CHTOP
gene, respectively. The present study demonstrated a system suitable for
evaluating the importance of variants in 5'UTRs affecting uORFs in 202 human
genes associated with hemoglobin expression. Research with this approach could
provide potential targets that may contribute to the clinical phenotypes and
provide biomarkers for precise diagnosis of beta-thalassemia.
PMID- 28420620
TI - Identification of LRP5 mutations in families with familial exudative
vitreoretinopathy.
AB - Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease
characterized by defects in the development of periphery retinal vessels.
However, the clinical phenotypes of FEVR vary widely from asymptomatic to
complete blindness. We analyzed patients from three Chinese families and one
sporadic patient with FEVR to investigate the clinical features and disease
causing mutations. Ocular phenotypes included increased ramification of the
peripheral retinal vessels, a peripheral avascular zone, inferotemporal dragging
of the optic disc and macula, and retinal folds. Peripheral blood DNA samples
were obtained from patients with FEVR and their family members. Primers were
designed to amplify the coding exons and adjacent intronic regions of the FEVR
causing genes FZD4, LRP5, NDP and TSPAN12. By polymerase chain reactions, each
amplicon was subjected to direct Sanger sequencing analysis. Potential pathogenic
changes of the sequence variants were analyzed by the orthologous protein
sequence alignment and computational prediction software. We identified five LRP5
mutations: three novel heterozygous mutations-p.M181R, p.R399S and p.G503R and
two known mutations that were never reported in FEVR patients: p.R494Q and
p.G876S. All five mutations involved highly conserved residues and were predicted
to be damaging by SIFT and PolyPhen-2. None was present in 500 normal
individuals. To assess the pathogenesis of these mutations, wild-type and all
five mutant LRP5 proteins were assayed for the ability to activate the
Norrin/beta-catenin pathway by established luciferase reporter assays, and all
mutants failed to activate the pathway. This study extends the genetic database
of the FEVR disease in China and provides a basis for molecular diagnosis of the
disease.
PMID- 28420621
TI - Association between polymorphisms of autophagy pathway and responses in non-small
cell lung cancer patients treated with platinum-based chemotherapy.
AB - Platinum-based chemotherapy is an important treatment for non-small cell lung
cancer. However, the effectiveness of the treatment varies among the patients. We
investigated the association between DNA polymorphisms of the autophagy pathway
and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs
located on 13 genes of the autophagy pathway were genotyped and assessed for
their association with clinical benefit, progression-free survival (PFS) and
overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR:
0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45
0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26
2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A)
(P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with
clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI:
0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM
gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene
were significantly associated with PFS. We also found that rs7953348 (G>A)
(P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A)
(P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS.
Thus, the study demonstrated that the autophagy pathway might play important
role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes
can potentially be predictors for clinical responses of platinum-based
chemotherapy among the patients with non-small lung cancer.
PMID- 28420623
TI - Externalised locking compression plate as an alternative to the unilateral
external fixator: a biomechanical comparative study of axial and torsional
stiffness.
AB - OBJECTIVES: External fixators are the traditional fixation method of choice for
contaminated open fractures. However, patient acceptance is low due to the high
profile and therefore physical burden of the constructs. An externalised locking
compression plate is a low profile alternative. However, the biomechanical
differences have not been assessed. The objective of this study was to evaluate
the axial and torsional stiffness of the externalised titanium locking
compression plate (ET-LCP), the externalised stainless steel locking compression
plate (ESS-LCP) and the unilateral external fixator (UEF). METHODS: A fracture
gap model was created to simulate comminuted mid-shaft tibia fractures using
synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS
LCP or UEF (five constructs each). The constructs were loaded under both axial
and torsional directions to determine construct stiffness. RESULTS: The mean
axial stiffness was very similar for UEF (528 N/mm) and ESS-LCP (525 N/mm), while
it was slightly lower for ET-LCP (469 N/mm). One-way analysis of variance (ANOVA)
testing in all three groups demonstrated no significant difference (F(2,12) =
2.057, p = 0.171).There was a significant difference in mean torsional stiffness
between the UEF (0.512 Nm/degree), the ESS-LCP (0.686 Nm/degree) and the ET-LCP
(0.639 Nm/degree), as determined by one-way ANOVA (F(2,12) = 6.204, p = 0.014). A
Tukey post hoc test revealed that the torsional stiffness of the ESS-LCP was
statistically higher than that of the UEF by 0.174 Nm/degree (p = 0.013). No
catastrophic failures were observed. CONCLUSION: Using the LCP as an external
fixator may provide a viable and attractive alternative to the traditional UEF as
its lower profile makes it more acceptable to patients, while not compromising on
axial and torsional stiffness.Cite this article: B. F. H. Ang, J. Y. Chen, A. K.
S. Yew, S. K. Chua, S. M. Chou, S. L. Chia, J. S. B. Koh, T. S. Howe.
Externalised locking compression plate as an alternative to the unilateral
external fixator: a biomechanical comparative study of axial and torsional
stiffness. Bone Joint Res 2017;6:216-223. DOI: 10.1302/2046-3758.64.2000470.
PMID- 28420624
TI - Five minutes with . . . Susan Lanham-New.
PMID- 28420625
TI - Sixty seconds on . . . teen pregnancies.
PMID- 28420627
TI - Encouraging young and old to interact in care settings.
PMID- 28420628
TI - Liposuction-induced fat embolism syndrome.
PMID- 28420630
TI - Ruth Kennedy.
PMID- 28420629
TI - Dexamethasone versus standard treatment for postoperative nausea and vomiting in
gastrointestinal surgery: randomised controlled trial (DREAMS Trial).
AB - : Objectives To determine whether preoperative dexamethasone reduces
postoperative vomiting in patients undergoing elective bowel surgery and whether
it is associated with other measurable benefits during recovery from surgery,
including quicker return to oral diet and reduced length of stay.Design Pragmatic
two arm parallel group randomised trial with blinded postoperative care and
outcome assessment.Setting 45 UK hospitals.Participants 1350 patients aged 18 or
over undergoing elective open or laparoscopic bowel surgery for malignant or
benign pathology.Interventions Addition of a single dose of 8 mg intravenous
dexamethasone at induction of anaesthesia compared with standard care.Main
outcome measures Primary outcome: reported vomiting within 24 hours reported by
patient or clinician. SECONDARY OUTCOMES: vomiting with 72 and 120 hours reported
by patient or clinician; use of antiemetics and postoperative nausea and vomiting
at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120
hours or discharge and at 30 days; time to return to fluid and food intake;
length of hospital stay; adverse events.Results 1350 participants were recruited
and randomly allocated to additional dexamethasone (n=674) or standard care
(n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred
in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated
standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22;
P=0.003). Additional postoperative antiemetics were given (on demand) to 265
(39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard
care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to
72 hours. There was no increase in complications.Conclusions Addition of a single
dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly
reduces both the incidence of postoperative nausea and vomiting at 24 hours and
the need for rescue antiemetics for up to 72 hours in patients undergoing large
and small bowel surgery, with no increase in adverse events.Trial registration
EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).
PMID- 28420631
TI - Health secretary orders inquiry into babies' deaths at Shrewsbury and Telford.
PMID- 28420632
TI - Paediatric traumatic pneumomediastinum: the spinnaker sail sign.
PMID- 28420633
TI - Fibrin sheath-associated endovascular infection of the heart: the Trojan horse of
indwelling central venous catheters.
AB - Chronic indwelling central venous catheters can result in formation of fibrin
sheaths increasing risk of occlusion, thrombosis and infection. Endovascular
infection of right-sided heart structures induced by such sheaths is very rare. A
48-year-old woman with end-stage renal disease initially treated for diabetic
ketoacidosis developed persistent Staphylococcus epidermidis bacteraemia without
an identifiable source. Although transthoracic echocardiography was unremarkable,
transoesophageal echocardiography revealed a fibrin sheath and vegetations in
superior vena cava-right atrium junction, which was the site of the tip of a
central catheter that had been removed 2 months prior, consistent with fibrin
sheath-associated endovascular infection. The bacteraemia cleared and clinical
improvement was seen with prolonged intravenous vancomycin. In patients with
unexplained bacteraemia and history of a central catheter, rare causes of
endovascular infections of right-sided heart structures like fibrin sheaths
should be considered. These can persist months after catheter removal.
Transoesophageal echocardiogram should be used for earlier detection.
PMID- 28420634
TI - Making the NHS and social care system sustainable.
PMID- 28420636
TI - Thomas George Price.
PMID- 28420635
TI - Lower urinary tract symptoms in an older man.
PMID- 28420637
TI - GPs urged to be cautious when assessing patients' fitness for endurance sports.
PMID- 28420638
TI - The BMJ Awards 2017: Cardiology.
PMID- 28420639
TI - Implementing shared decision making in the NHS: lessons from the MAGIC programme.
PMID- 28420640
TI - Margaret McCartney: Why ask, if you ignore the answer?
PMID- 28420641
TI - Should we intubate patients during cardiopulmonary resuscitation?
PMID- 28420642
TI - Vanguards start to change practice but will lessons be applied nationwide?
PMID- 28420643
TI - Isolated implant metastasis in chest wall due to seeding of transpleurally placed
PTBD catheter tract in a case of hilar cholangiocarcinoma.
AB - Percutaneous transhepatic biliary drainage (PTBD) catheter site metastasis in
cases of cholangiocarcinoma is reported sporadically. But it is unusual to see
left-sided tumour metastasising to the right PTBD catheter site. Metastasis, in
general, has a poor prognosis, but recurrence along the catheter tract in the
absence of other systemic diseases can be a different scenario altogether. To
date, there is no consensus on the management of this form of metastasis. But
carefully selected patients can benefit from aggressive surgical resection. We
report a case of a young patient with isolated chest wall metastasis 1 year after
resection of left-sided hilar cholangiocarcinoma. The metastasis was resected
and, on pathological analysis, was confirmed to be due to implantation of
malignant cells along the tract of the PTBD catheter placed via a transpleural
route.
PMID- 28420644
TI - Smokers and Postcessation Weight Gain After Acute Coronary Syndrome.
AB - BACKGROUND: Smoking cessation and weight management are recommended after acute
coronary syndrome (ACS); however, little is known about the effects of smoking
cessation on weight change after ACS. We aimed to assess the effect of smoking
cessation after ACS on weight over a 12-month follow-up period. METHODS AND
RESULTS: Data were prospectively collected from the EVITA (Evaluation of
Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome)
trial. Weight change was compared among 3 groups of patients: those who were
completely abstinent (n=70), those who smoked intermittently (n=68), and those
who smoked persistently (n=34). Patients' mean baseline weight was 83.9 kg (SD
17.7) with a mean body mass index of 28.5 (SD 5.4). Patients smoked a mean of
37.7 years (SD 17.7) and a mean of 21.0 cigarettes (SD 9.0) per day prior to
their ACS. Weight change varied across groups, with abstainers gaining a mean of
4.8 kg (SD 8.6), intermittent smokers gaining a mean of 2.0 kg (SD 8.9) and
persistent smokers losing a mean of 0.7 kg (SD 7.4). At 52 weeks, abstainers were
more likely to gain weight than persistent smokers (difference in means 5.5 kg;
95% CI 2.3-8.8). This weight gain was not associated with an increase in the use
of antihypertensive or antidiabetic medications. CONCLUSIONS: Following an ACS,
significant weight is gained by patients who quit smoking. Weight-management
interventions among smokers who quit after ACS should be a focus of investigation
in future research so that the cardiovascular benefits achieved by smoking
cessation are not offset by weight gain in this high-risk population. CLINICAL
TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
NCT00794573.
PMID- 28420645
TI - Association Between Chronic Kidney Disease and Rates of Transfusion and
Progression to End-Stage Renal Disease in Patients Undergoing Transradial Versus
Transfemoral Cardiac Catheterization-An Analysis From the Veterans Affairs
Clinical Assessment Reporting and Tracking (CART) Program.
AB - BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for
bleeding, transfusion, and dialysis after cardiac catheterization. Whether rates
of these complications are increased in this high-risk population undergoing
transradial access compared with transfemoral access is unknown. METHODS AND
RESULTS: From the Veterans Affairs (VA) Clinical Assessment Reporting and
Tracking program, we identified 229 108 patients undergoing cardiac
catheterization between 2007 and 2014, of which 48 155 (21.0%) had baseline
glomerular filtration rate (GFR) between 15 and 59 mL/min. We used multivariable
Cox modeling to determine the independent association between transradial access
and postprocedure transfusion as well as progression to new dialysis by degree of
renal dysfunction. Overall, 35 979 (15.7%) of patients underwent Transradial
access. Transradial patients tended to be slightly younger, but, overall, had
similar rates of CKD compared to transfemoral patients (24.3% vs 27.1%).
Transradial patients had longer fluoroscopy times (7.2 vs 6.0 minutes; P<0.001),
but lower contrast use (85.0 vs 100.0 mL; P<0.001). The estimated rate of blood
transfusion within 48 hours was lower among transradial patients (0.85% vs 1.01%)
as were rates of new dialysis at 1 year (0.58% vs 0.71%). After multivariable
adjustment, transradial access was associated with lower rates of progression to
dialysis at 1 year overall (hazard ratio [HR], 0.83; 95% CI, 0.70-0.98), with no
trend of increased risk for dialysis by degree of CKD compared with transfemoral
access. Transradial access was associated with greater reduction in transfusion
rates with increasing degree of CKD (P value for trend=0.04: non-CKD: HR, 0.99;
95% CI, 0.73-1.34; GFR 45-59 mL/min: HR, 0.93; 95% CI, 0.70-1.23; GFR 30-44
mL/min: HR, 0.73; 95% CI, 0.51-1.03; GFR 15-29 mL/min: HR, 0.43; 95% CI, 0.20
0.90). CONCLUSIONS: Among patients undergoing cardiac catheterization in the VA
health system, transradial access was associated with lower risk for
postprocedure transfusion within 48 hours among patients with more-severe CKD,
and with lower risk of progression to end-stage renal disease at 1 year compared
with transfemoral access. These data provide additional evidence that transradial
access may provide significant benefit in this high-risk population.
PMID- 28420646
TI - Associations Between Left Ventricular Dysfunction and Brain Structure and
Function: Findings From the SABRE (Southall and Brent Revisited) Study.
AB - BACKGROUND: Subclinical left ventricular (LV) dysfunction has been inconsistently
associated with early cognitive impairment, and mechanistic pathways have been
poorly considered. We investigated the cross-sectional relationship between LV
dysfunction and structural/functional measures of the brain and explored the role
of potential mechanisms. METHOD AND RESULTS: A total of 1338 individuals (69+/-6
years) from the Southall and Brent Revisited study underwent echocardiography for
systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial
diameter) assessment. Cognitive function was assessed and total and hippocampal
brain volumes were measured by magnetic resonance imaging. Global LV function was
assessed by circulating N-terminal pro-brain natriuretic peptide. The role of
potential mechanistic pathways of arterial stiffness, atherosclerosis,
microvascular disease, and inflammation were explored. After adjusting for age,
sex, and ethnicity, lower systolic function was associated with lower total brain
(beta+/-standard error, 14.9+/-3.2 cm3; P<0.0001) and hippocampal volumes (0.05+/
0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working
memory (-0.21+/-0.07, P=0.004) and fluency scores (-0.18+/-0.08, P=0.02). Reduced
global LV function was associated with smaller hippocampal volume (-0.10+/-0.03
cm3, P=0.004) and adverse visual memory (-0.076+/-0.03, P=0.02) and processing
speed (0.063+/-0.02, P=0.006) scores. Separate adjustment for concomitant
cardiovascular risk factors attenuated associations with hippocampal volume and
fluency only. Further adjustment for the alternative pathways of microvascular
disease or arterial stiffness attenuated the relationship between global LV
function and visual memory. CONCLUSIONS: In a community-based sample of older
people, measures of LV function were associated with structural/functional
measures of the brain. These associations were not wholly explained by
concomitant risk factors or potential mechanistic pathways.
PMID- 28420647
TI - Incremental Value of Transthoracic Doppler Echocardiography-Assessed Coronary
Flow Reserve in Patients With Suspected Myocardial Ischemia Undergoing Myocardial
Perfusion Scintigraphy.
AB - BACKGROUND: Adenosine-assisted transthoracic Doppler-derived coronary flow
reserve (TDE-CFR) reflects coronary vascular function. The prognostic and
incremental value of left anterior descending coronary artery TDE-CFR above
myocardial perfusion scintigraphy in patients with suspected myocardial ischemia
has not yet been studied. METHODS AND RESULTS: Three hundred seventy-one patients
(mean age, 62.3+/-8.7 years; 46.8% males) referred to myocardial perfusion
scintigraphy attributed to suspected myocardial ischemia were included in the
study. The TDE-CFR result was blinded to the referring physician. Patients were
followed up regarding major cardiovascular events, defined as cardiovascular
death, myocardial infarction, or acute revascularization during a median follow
up time of 4.5 years. A TDE-CFR value of <=2.0 was considered reduced. Major
cardiovascular events occurred during follow-up in 60 patients (16.2%). A reduced
TDE-CFR was detected in 76 patients (20.5%). Patients with reduced TDE-CFR had an
event rate of 36.8% compared to 10.8% in patients with normal TDE-CFR (unadjusted
hazard ratio, 4.63; 95% CI, 2.78-7.69; P<0.001). In a multivariate model, TDE-CFR
remained a significant independent predictor of major cardiovascular events. The
major cardiovascular events rate was 7.5% in patients without myocardial
perfusion scintigraphy-detected myocardial ischemia and normal TDE-CFR (n=200),
24.2% in patients without ischemia but with reduced TDE-CFR (n=33), and 46.5% in
patients with both myocardial perfusion scintigraphy-detected myocardial ischemia
and a reduced TDE-CFR (n=43; P<0.001). CONCLUSIONS: Coronary microvascular
dysfunction, as determined by TDE-CFR, is a strong independent predictor of
cardiovascular events and adds incremental prognostic value compared with
myocardial perfusion scintigraphy. The current study supports routine assessment
of CFR in patients with suspected ischemic heart disease.
PMID- 28420648
TI - Association of Magnet Status With Hospitalization Outcomes for Ischemic Stroke
Patients.
AB - BACKGROUND: It is not clear whether Magnet recognition by the American Nurses
Credentialing Center (nursing excellence program) is associated with improved
patient outcomes. We investigated whether hospitalization in a Magnet hospital is
associated with improved outcomes for patients with ischemic stroke. METHODS AND
RESULTS: We performed a cohort study of patients with ischemic stroke from 2009
to 2013, who were registered in the New York Statewide Planning and Research
Cooperative System database. Propensity-score-adjusted multivariable regression
models were used to adjust for known confounders, with mixed effects methods to
control for clustering at the facility level. An instrumental variable analysis
was used to control for unmeasured confounding and simulate the effect of a
randomized trial. During the study period, 176 557 patients were admitted for
ischemic stroke, and met the inclusion criteria. Of these, 32 092 (18.2%) were
hospitalized in Magnet hospitals, and 144 465 (81.8%) in non-Magnet institutions.
Instrumental variable analysis demonstrated that hospitalization in Magnet
hospitals was associated with lower case-fatality (adjusted difference, -23.9%;
95% CI, -29.0% to -18.7%), length of stay (adjusted difference, -0.4; 95% CI,
0.8 to -0.1), and rate of discharge to a facility (adjusted difference, -16.5%;
95% CI, -20.0% to -13.0%) in comparison to non-Magnet hospitals. The same
associations were present in propensity-score-adjusted mixed effects models.
CONCLUSIONS: Using a comprehensive all-payer cohort of patients with ischemic
stroke in New York State, we identified an association of treatment in Magnet
hospitals with lower case-fatality, discharge to a facility, and length of stay.
Further research into the factors contributing to the superiority of Magnet
hospitals in stroke care is warranted.
PMID- 28420649
TI - A sandwich ELISA for measurement of the primary glucagon-like peptide-1
metabolite.
AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the
gastrointestinal tract. It is best known for its glucose-dependent insulinotropic
effects. GLP-1 is secreted in its intact (active) form (7-36NH2) but is rapidly
degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the
primary metabolite (9-36NH2) before reaching the targets via the circulation.
Although originally thought to be inactive or antagonistic, GLP-1 9-36NH2 may
have independent actions, and it is therefore relevant to be able to measure it.
Because reliable assays were not available, we developed a sandwich ELISA
recognizing both GLP-1 9-36NH2 and nonamidated GLP-1 9-37. The ELISA was
validated using analytical assay validation guidelines and by comparing it to a
subtraction-based method, hitherto employed for estimation of GLP-1 9-36NH2 Its
accuracy was evaluated from measurements of plasma obtained during intravenous
infusions (1.5 pmol * kg-1 * min-1) of GLP-1 7-36NH2 in healthy subjects and
patients with type 2 diabetes. Plasma levels of the endogenous GLP-1 metabolite
increased during a meal challenge in patients with type 2 diabetes, and treatment
with a DPP-4 inhibitor fully blocked its formation. Accurate measurements of the
GLP-1 metabolite may contribute to understanding its physiology and role of GLP-1
in diabetes.
PMID- 28420651
TI - Anorectal involvement in a patient with multiple myeloma.
AB - Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells.
Symptomatic gastrointestinal involvement is uncommon. We report the case of a 45
year-old patient admitted with an anorectal polypoid lesion, which progressed to
colonic obstruction. Investigation revealed a secondary plasmacytoma associated
with multiple myeloma. We discuss the characteristics of this rare entity with
poor prognosis, its clinical implications and treatment options.
PMID- 28420650
TI - Changes in LXR signaling influence early-pregnancy lipogenesis and protect
against dysregulated fetoplacental lipid homeostasis.
AB - Human pregnancy is associated with enhanced de novo lipogenesis in the early
stages followed by hyperlipidemia during advanced gestation. Liver X receptors
(LXRs) are oxysterol-activated nuclear receptors that stimulate de novo
lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues
followed by its transport back to the liver for biliary excretion. Although LXR
is recognized as a master regulator of triglyceride and cholesterol homeostasis,
it is unknown whether it facilitates the gestational adaptations in lipid
metabolism. To address this question, biochemical profiling, protein
quantification, and gene expression studies were used, and gestational metabolic
changes in T0901317-treated wild-type mice and Lxrab-/- mutants were
investigated. Here, we show that altered LXR signaling contributes to the
enhanced lipogenesis in early pregnancy by increasing the expression of hepatic
Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of
LXR with T0901317 and the genetic ablation of its two isoforms disrupted the
increase in hepatic fatty acid biosynthesis and the development of
hypertriglyceridemia during early gestation. We also demonstrate that absence of
LXR enhances maternal white adipose tissue lipolysis, causing abnormal
accumulation of triglycerides, cholesterol, and free fatty acids in the fetal
liver. Together, these data identify LXR as an important factor in early
pregnancy lipogenesis that is also necessary to protect against abnormalities in
fetoplacental lipid homeostasis.
PMID- 28420653
TI - David Oliver: Choosing to be honest about patient choice.
PMID- 28420652
TI - Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER
Consortium.
AB - Background: Alcohol is a recognized risk factor for invasive breast cancer, but
few studies involve African American women.Methods: The current analysis included
22,338 women (5,108 cases of invasive breast cancer) from the African American
Breast Cancer Epidemiology and Risk (AMBER) Consortium. The association between
number of alcoholic drinks per week (dpw) and breast cancer was estimated using
logistic regression, adjusting for potential confounders, and stratifying by
breast cancer subtype.Results: Approximately 35% of controls were current
drinkers at interview. Women who reported current drinking of >=14 dpw had an
elevated risk of breast cancer compared with light drinkers (>0-<4 dpw) [adjusted
OR (ORadj), 1.33; 95% confidence interval (CI), 1.07-1.64]. We observed elevated
risk among women drinking >=7 dpw for ER - [ORadj, 1.31; 95% CI, 1.00-1.72], PR -
[ORadj, 1.28; 95% CI, 1.00-1.63], HER2 - [ORadj, 1.36; 95% CI, 1.09-1.70], and
triple-negative [ORadj, 1.39; 95% CI, 0.98-2.00] molecular subtype. Among
receptor-positive cases, ORs remained elevated but attenuated relative to
receptor-negative cases. Sensitivity analysis of age-defined windows of exposure
(<30 years, 30-49, 50+ years of age) did not reveal variation in patterns of
association. Risk associated with alcohol intake did not vary significantly by
oral contraceptive use, smoking status, or menopausal status.Conclusions: Among
African American women, similar to women of European descent, drinking >=7
alcoholic dpw was associated with an increased risk of breast cancer regardless
of subtype.Impact: Alcohol intake is a modifiable risk factor for breast cancer,
and reduced intake among African American women should be encouraged. Cancer
Epidemiol Biomarkers Prev; 26(5); 787-94. (c)2017 AACR.
PMID- 28420654
TI - Changes in the Profile of Endovascular Procedures Performed in Freestanding
Dialysis Access Centers over 15 Years.
AB - BACKGROUND AND OBJECTIVES: Marked changes occurred in the vascular access profile
of patients receiving hemodialysis in the United States over the 15-year period
of 2001-2015. This study was undertaken to evaluate how these changes have
affected dialysis access maintenance and salvage procedures performed in
freestanding dialysis access centers and to examine the effectiveness,
efficiency, and safety of these procedures in this setting. DESIGN, SETTING,
PARTICIPANTS, & MEASUREMENTS: Data were collected from freestanding, dedicated
dialysis access centers operating under a common system of management. Data were
available on 689,676 dialysis access procedures. Data relating to case mix,
procedure outcome, procedural time, and intraprocedural and immediate
postprocedural complications were analyzed. RESULTS: The arteriovenous procedure
profile changed from one characterized by approximately equal numbers of
angioplasties and thrombectomies performed on arteriovenous grafts (AVGs) to one
characterized primarily by angioplasties performed on arteriovenous fistulas. The
percentage of angioplasties performed throughout the study was significantly
greater than thrombectomies, with a mean of 67.9% versus 32.1% (P<0.001).
Interventional procedures did not decrease with increasing arteriovenous fistula
utilization in prevalent patients receiving dialysis. The incidence roughly
paralleled the increasing prevalence of this type of access. A decreasing
percentage of AVG utilization resulted in a progressive, roughly parallel, but
disproportionately higher, decrease in the percentage of AVG procedures
(P<0.001). A progressive improvement in procedure outcomes and a decrease in
complication rates and procedure times were observed (P<0.001 for each). A
progressive decrease in tunneled dialysis catheter placement was also observed.
CONCLUSIONS: The procedure profile treated in freestanding, dedicated dialysis
access centers changed significantly over 15 years, reflecting the changes that
have occurred in the vascular access profile of the dialysis population.
PMID- 28420655
TI - Syncope and Its Impact on Occupational Accidents and Employment: A Danish
Nationwide Retrospective Cohort Study.
AB - BACKGROUND: First-time syncopal episodes usually occur in adults of working age,
but their impact on occupational safety and employment remains unknown. We
examined the associations of syncope with occupational accidents and termination
of employment. METHODS AND RESULTS: Through linkage of Danish population-based
registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3
410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were
identified, with a median age 48.4 years (first to third quartiles, 33.0-59.5),
and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up
of 3.2 years (first to third quartiles, 2.0-4.5), 622 people with syncope had an
occupational accident requiring hospitalization (2.1/100 person-years). In
multiple Poisson regression analysis, the incidence rate ratio in the employed
syncope population was higher than in the employed general population (1.44; 95%
confidence interval [CI], 1.33-1.55) and more pronounced in people with
recurrences (2.02; 95% CI, 1.47-2.78). The 2-year risk of termination of
employment was 31.3% (95% CI, 30.4%-32.3%), which was twice the risk of the
reference population (15.2%; 95% CI, 14.7%-15.7%), using the Aalen-Johansen
estimator. Factors associated with termination of employment were age <40 years
(incidence rate ratio, 1.48; 95% CI, 1.37-1.59), cardiovascular disease (1.20;
95% CI, 1.06-1.36), depression (1.72; 95% CI, 1.55-1.90), and low educational
level (2.61; 95% CI, 2.34-2.91). CONCLUSIONS: In this nationwide cohort, syncope
was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold
higher risk of termination of employment compared with the employed general
population.
PMID- 28420657
TI - A neural basis for password-based species recognition in an avian brood parasite.
AB - Obligate avian brood parasites are raised by heterospecific hosts and, therefore,
lack crucial early exposure to relatives and other conspecifics. Yet, young brood
parasites readily recognize and affiliate with others of their own species upon
independence. One solution to this social recognition paradox is the ontogenetic
'password' mechanism used by obligate parasitic brown-headed cowbirds (Molothrus
ater), whereby conspecific identification is initially mediated through the
cowbird chatter: a non-learned vocal cue. We explored the neural basis of such
password-based species recognition in juvenile and adult male cowbirds. We found
that cowbird auditory forebrain regions express greater densities of the protein
product of the immediate-early gene ZENK in response to the password chatter call
relative to control sounds of mourning dove (Zenaida macroura) coos. The chatter
selective induction of ZENK expression occurs in both the caudal medial
nidopallium (NCM) and the caudal medial mesopallium (CMM) in adults, but only
within the NCM in juveniles. In contrast, we discovered that juvenile cowbirds
exhibit neural selectivity to presentations of either conspecific or
heterospecific songs, but only in CMM and only after recent experience. Juvenile
cowbirds that did not have previous experience with the song type they were
exposed to during the test period exhibited significantly lower activity
dependent gene expression. Thus, in juvenile male cowbirds, there is early onset
of species-specific selective neural representation of non-learned calls in NCM
and recently experienced song in CMM. These results suggest that NCM is
evolutionarily co-opted in parasitic cowbirds to selectively recognize the
password chatter, allowing juvenile cowbirds to identify adult conspecifics and
avoid mis-imprinting upon unrelated host species. These ontogenetic comparisons
reveal novel insights into the neural basis of species recognition in brood
parasitic species.
PMID- 28420656
TI - Posttranslational modification impact on the mechanism by which amyloid-beta
induces synaptic dysfunction.
AB - Oligomeric amyloid-beta (Abeta) 1-42 disrupts synaptic function at an early stage
of Alzheimer's disease (AD). Multiple posttranslational modifications of Abeta
have been identified, among which N-terminally truncated forms are the most
abundant. It is not clear, however, whether modified species can induce synaptic
dysfunction on their own and how altered biochemical properties can contribute to
the synaptotoxic mechanisms. Here, we show that a prominent isoform,
pyroglutamated Abeta3(pE)-42, induces synaptic dysfunction to a similar extent
like Abeta1-42 but by clearly different mechanisms. In contrast to Abeta1-42,
Abeta3(pE)-42 does not directly associate with synaptic membranes or the prion
protein but is instead taken up by astrocytes and potently induces glial release
of the proinflammatory cytokine TNFalpha. Moreover, Abeta3(pE)-42-induced
synaptic dysfunction is not related to NMDAR signalling and Abeta3(pE)-42-induced
impairment of synaptic plasticity cannot be rescued by D1-agonists. Collectively,
the data point to a scenario where neuroinflammatory processes together with
direct synaptotoxic effects are caused by posttranslational modification of
soluble oligomeric Abeta and contribute synergistically to the onset of synaptic
dysfunction in AD.
PMID- 28420658
TI - Simple and rapid biochemical method to synthesize labeled or unlabeled
phosphatidylinositol species.
AB - Phosphatidylinositol (PI) is the precursor of many important signaling molecules
in eukaryotic cells and, most probably, PI also has important functions in
cellular membranes. However, these functions are poorly understood, which is
largely due to that i) only few PI species with specific acyl chains are
available commercially and ii) there are no simple methods to synthesize such
species. Here, we present a simple biochemical protocol to synthesize a variety
of labeled or unlabeled PI species from corresponding commercially available
phosphatidylcholines. The protocol can be carried out in a single vial in a two
step process which employs three enzymatic reactions mediated by i) commercial
phospholipase D from Streptomyces chromofuscus, ii) CDP-diacylglycerol synthase
overexpressed in E. coli and iii) PI synthase of Arabidopsis thaliana ectopically
expressed in E. coli The PI product is readily purified from the reaction mixture
by liquid chromatography since E. coli does not contain endogenous PI or other
coeluting lipids. The method allows one to synthesize and purify labeled or
unlabeled PI species in 1 or 2 days.Typically, 40-60% of (unsaturated) PC was
converted to PI albeit the final yield of PI was less (25-35%) due to losses upon
purification.
PMID- 28420659
TI - Very low expression of PD-L1 in medullary thyroid carcinoma.
PMID- 28420660
TI - Education achievement and type 2 diabetes-what mediates the relationship in older
adults? Data from the ESTHER study: a population-based cohort study.
AB - OBJECTIVE: The study aims to identify the mediating factors of the relationship
between education achievement and incident type 2 diabetes mellitus (T2DM) in
older adults. DESIGN: Population-based cohort study. SETTING: Participants were
recruited from the German federal state of Saarland. PARTICIPANTS: Participants
were excluded if they had prevalent T2DM or missing data on prevalent T2DM,
missing or zero follow-up time for incident T2DM or were under 50 years of age.
The total sample consisted of 7462 individuals aged 50-75 years (42.8% men, mean
age 61.7 years) at baseline (2000-02). The median follow-up time was 8.0 years.
METHODS: Cox proportional hazards regression was initially used to determine the
direct association between education achievement and incident T2DM. Using the
Baron and Kenny approach, we then investigated the associations between education
achievement and incident T2DM with the potential mediators. The contribution of
each of the putative mediating variables was then calculated. RESULTS: A clear
socioeconomic gradient was observed with regard to T2DM incidence with the lowest
educated individuals at a greater risk of developing the disease during the
follow-up period: HR (95% CI) high education: 0.52 (0.34 to 0.80); medium
education: 0.80 (0.66 to 0.96). Seven of the variables considered explained a
proportion of the education-T2DM relationship (body mass index, alcohol
consumption, hypertension, fasting triglycerides, high-density lipoprotein (HDL)
cholesterol, physical activity and smoking status), where the contribution of the
variables ranged from 1.0% to 17.7%. Overall, the mediators explained 31.7% of
the relationship. CONCLUSION: By identifying the possible mediating factors of
the relationship between education achievement and incident T2DM in older adults,
the results of this study can be used to assist with the development of public
health strategies that aim to reduce socioeconomic inequalities in T2DM.
PMID- 28420661
TI - Person-centred transition programme to empower adolescents with congenital heart
disease in the transition to adulthood: a study protocol for a hybrid randomised
controlled trial (STEPSTONES project).
AB - INTRODUCTION: When a young person grows up, they evolve from an independent child
to an empowered adult. If an individual has a chronic condition, this additional
burden may hamper adequate development and independence. Transition programmes
for young persons with chronic disorders aim to provide the necessary skills for
self-management and participation in care. However, strong evidence on the
effects of these interventions is lacking. Therefore, as part of the STEPSTONES
project (Swedish Transition Effects Project Supporting Teenagers with chrONic
mEdical conditionS), we propose a trial to assess the effectiveness of a
structured, person-centred transition programme to empower adolescents with
congenital heart disease in the transition to adulthood. METHODS/DESIGN:
STEPSTONES will use a hybrid experimental design in which a randomised controlled
trial is embedded in a longitudinal, observational study. It will be conducted in
4 paediatric cardiology centres in Sweden. 2 centres will be allocated to the
randomised controlled trial group, assigning patients randomly to the
intervention group (n=63) or the comparison group (n=63). The other 2 centres
will form the intervention-naive control group (n=63). The primary outcome is the
level of patient empowerment, as measured by the Gothenburg Young Persons
Empowerment Scale (GYPES). ETHICS AND DISSEMINATION: The study has been approved
by the Regional Ethical Board of Gothenburg, Sweden. Findings will be reported
following the CONSORT statement and disseminated at international conferences and
as published papers in peer-reviewed journals. TRIAL REGISTRATION NUMBER:
NCT02675361; pre-results.
PMID- 28420662
TI - Outcome of a screening programme for the prevention of neonatal invasive early
onset group B Streptococcus infection in a UK maternity unit: an observational
study.
AB - BACKGROUND: Against a background of failure to prevent neonatal invasive early
onset group B Streptococcus infections (GBS) in our maternity unit using risk
based approach for intrapartum antibiotic prophylaxis, we introduced an antenatal
GBS carriage screening programme to identify additional women to target for
prophylaxis. OBJECTIVES: To describe the implementation and outcome of an
antepartum screening programme for prevention of invasive early-onset GBS
infection in a UK maternity unit. DESIGN: Observational study of outcome of
screening programme (intervention) with comparison to historical controls
(preintervention). SETTING: Hospital and community-based maternity services
provided by Northwick Park and Central Middlesex Hospitals in North West London.
PARTICIPANTS: Women who gave birth between March 2014 and December 2015 at
Northwick Park Hospital. METHODS: Women were screened for GBS at 35-37 weeks and
carriers offered intrapartum antibiotic prophylaxis. Screening programme was
first introduced in hospital (March 2014) and then in community (August 2014).
Compliance was audited by review of randomly selected case records. Invasive
early-onset GBS infections were defined through GBS being cultured from neonatal
blood, cerebrospinal fluid or sterile fluids within 0-6 days of birth. MAIN
OUTCOME: Incidence of early-onset GBS infections. RESULTS: 6309 (69%) of the 9098
eligible women were tested. Screening rate improved progressively from 42% in
2014 to 75% in 2015. Audit showed that 98% of women accepted the offer of
screening. Recto-vaginal GBS carriage rate was 29.4% (1822/6193). All strains
were susceptible to penicillin but 11.3% (206/1822) were resistant to
clindamycin. Early onset GBS rate fell from 0.99/1000 live births (25/25276) in
the prescreening period to 0.33/1000 in the screening period (Rate Ratio=0.33;
p=0.08). In the subset of mothers actually screened, the rate was 0.16/1000 live
births (1/6309), (Rate Ratio=0.16; p<0.05). CONCLUSIONS: Our findings confirm
that an antenatal screening programme for prevention of early-onset GBS infection
can be implemented in a UK maternity setting and is associated with a fall in
infection rates.
PMID- 28420663
TI - Optimal body fat percentage cut-off values for identifying cardiovascular risk
factors in Mongolian and Han adults: a population-based cross-sectional study in
Inner Mongolia, China.
AB - OBJECTIVE: The present study was designed to determine the optimal cut-off values
of body fat percentage (BF%) for the detection of cardiovascular disease (CVD)
risk factors in Mongolian and Han adults. METHOD: This cross-sectional study
involving 3221 Chinese adults (2308 Han and 913 Mongolian) aged 20-80 years was
conducted in Inner Mongolia Autonomous Region, China, in 2014. Data from a
standardised questionnaire, physical examination and blood sample were obtained.
The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut
offs were analysed by receiver operating characteristic curves to predict the
risk of diabetes, hypertension and dyslipidaemia. Binary logistic regression
analysis was performed to evaluate the OR of each CVD risk factor according to
obesity defined by BF%. RESULTS: Mean BF% levels were lower in men than in women
(22.54+/-5.77 vs 32.95+/-6.18 in Han, 23.86+/-5.72 vs 33.98+/-6.40 in Mongolian
population, respectively; p<0.001). In Han population, the area under curve (AUC)
values for BF% ranged from 0.589 to 0.699 for men and from 0.711 to 0.763 for
women. Compared with men, AUCs for diabetes and clustering of >=2 risk factors in
women were significantly higher (p<0.05). The AUCs for BF% in women (0.685-0.783)
were similar with those in men (0.686-0.736) for CVD risk factors in Mongolian
population. In Han adults, the optimal BF% cut-off values to detect CVD risk
factors varied from 18.7% to 24.2% in men and 32.7% to 35.4% in women. In
Mongolian population, the optimal cut-off values of BF% for men and women ranged
from 21.0% to 24.6% and from 35.7% to 40.0%, respectively. Subjects with high BF%
(>=24% in men, >=34% in women) had higher risk of CVD risk factors in Han (age
adjusted ORs from 1.479 to 3.680, 2.660 to 4.016, respectively). In Mongolia,
adults with high BF% (>=25% in men, >=35% in women) had higher risk of CVD risk
factors (age-adjusted ORs from 2.587 to 3.772, 2.061 to 4.882, respectively).
CONCLUSIONS: The optimal BF% cut-offs for obesity for the prediction of CVD risk
factors in Chinese men and women were approximately 24% and 34% for Han adults
and 25% and 35% for Mongolian population of Inner Mongolia, China, respectively.
PMID- 28420665
TI - Correction.
PMID- 28420664
TI - The UK Cardiac and Vascular Surgery Interventional Anaemia Response (CAVIAR)
Study: protocol for an observational cohort study to determine the impact and
effect of preoperative anaemia management in cardiac and vascular surgical
patients.
AB - INTRODUCTION: Preoperative anaemia is linked to poor postsurgical outcome, longer
hospital stays, greater risk of complications and mortality. Currently in the UK,
some sites have developed anaemia clinics or pathways that use intravenous iron
to correct iron deficiency anaemia prior to surgery as their standard of care.
Although intravenous iron has been observed to be effective in a variety of
patient settings, there is insufficient evidence in its use in cardiac and
vascular patients. The aim of this study is to observe the impact and effect of
anaemia and its management in patients undergoing cardiac and vascular surgery.
In addition, the UK Cardiac and Vascular Surgery Interventional Anaemia Response
(CAVIAR) Study is also a feasibility study with the aim to establish anaemia
management pathways in the preoperative setting to inform the design of future
randomised controlled trials. METHODS AND ANALYSIS: The UK CAVIAR Study is a
multicentre, stepped, observational study, in patients awaiting major cardiac or
vascular surgery. We will be examining different haematological variables
(especially hepcidin), functional capacity and patient outcome. Patients will be
compared based on their anaemia status, whether they received intravenous iron in
accordance to their hospital's preoperative pathway, and their disease group. The
primary outcomes are the change in haemoglobin levels from baseline (before
treatment) to before surgery; and the number of successful patients recruited and
consented (feasibility). The secondary outcomes will include changes in
biomarkers of iron deficiency, length of stay, quality of life and postoperative
recovery. ETHICS AND DISSEMINATION: The study protocol was approved by the London
Westminster Research Ethics Committee (15/LO/1569, 27 November 2015). NHS
approval was also obtained with each hospital trust. The findings of the study
will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical
Trials registry (NCT02637102) and the ISRCTN registry (ISRCTN55032357).
PMID- 28420666
TI - Prevalence and Clinical Implication of Double Mutations in Hypertrophic
Cardiomyopathy: Revisiting the Gene-Dose Effect.
AB - BACKGROUND: Available data suggests that double mutations in patients with
hypertrophic cardiomyopathy are not rare and are associated with a more severe
phenotype. Most of this data, however, is based on noncontemporary variant
classification. METHODS AND RESULTS: Clinical data of all hypertrophic
cardiomyopathy patients with 2 rare genetic variants were retrospectively
reviewed and compared with a group of patients with a single disease-causing
variant. Furthermore, a literature search was performed for all studies with
information on prevalence and outcome of patients with double mutations.
Classification of genetic variants was reanalyzed according to current
guidelines. In our cohort (n=1411), 9% of gene-positive patients had 2 rare
variants in sarcomeric genes but only in 1 case (0.4%) were both variants
classified as pathogenic. Patients with 2 rare variants had a trend toward
younger age at presentation when compared with patients with a single mutation.
All other clinical variables were similar. In data pooled from cohort studies in
the literature, 8% of gene-positive patients were published to have double
mutations. However, after reanalysis of reported variants, this prevalence
diminished to 0.4%. All patients with 2 radical mutations in MYBPC3 in the
literature had severe disease with death or heart transplant during the first
year of life. Data on other specific genotype-phenotype correlations were scarce.
CONCLUSIONS: Double mutations in patients with hypertrophic cardiomyopathy are
much less common than previously estimated. With the exception of double radical
MYBPC3 mutations, there is little data to guide clinical decision making in cases
with double mutations.
PMID- 28420667
TI - Are Double Mutations Double Trouble?
PMID- 28420668
TI - Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.
AB - RATIONALE: The liver is the central organ that responds to dietary cholesterol
intake and facilitates the release and clearance of lipoprotein particles.
Persistent hypercholesterolemia leads to immune responses against lipoprotein
particles that drive atherosclerosis. However, the effect of hypercholesterolemia
on hepatic T-cell differentiation remains unknown. OBJECTIVE: To investigate
hepatic T-cell subsets upon hypercholesterolemia. METHODS AND RESULTS: We
observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg)
cell population and increased the expression of transforming growth factor-beta1
in the liver. Adoptive transfer experiments revealed that intrahepatically
differentiated Treg cells relocated to the inflamed aorta in atherosclerosis
prone low-density lipoprotein receptor deficient (Ldlr-/-) mice. Moreover,
hypercholesterolemia induced the differentiation of intrahepatic, but not
intrasplenic, Th17 cells in wild-type mice, whereas the disrupted liver
homeostasis in hypercholesterolemic Ldlr-/- mice led to intrahepatic Th1 cell
differentiation and CD11b+CD11c+ leukocyte accumulation. CONCLUSIONS: Our results
elucidate a new mechanism that controls intrahepatic T-cell differentiation
during atherosclerosis development and indicates that intrahepatically
differentiated T cells contribute to the CD4+ T-cell pool in the atherosclerotic
aorta.
PMID- 28420670
TI - Confirmed early myocardial rupture in a patient with pulseless electrical
activity (PEA) following late presentation of ST elevation myocardial infarction.
PMID- 28420669
TI - A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming
Growth Factor beta-1 to Soluble Endoglin Ratio.
AB - RATIONALE: The pathogenesis of bicuspid aortic valve (BAV)-associated aortopathy
is poorly understood, and no prognostic biomarker is currently available.
OBJECTIVE: We aimed to identify putative circulating biomarkers pathogenetically
and prognostically linked to bicuspid aortopathy. METHODS AND RESULTS: By reverse
transcription polymerase chain reaction, we evaluated gene expression variations
(versus normal aorta) of transforming growth factor-beta1 (TGF-beta1), connective
tissue growth factor, matrix metalloproteinase-2 (MMP-2), MMP-14, endoglin (ENG),
and superoxide dismutase 3 in ascending aorta samples from 50 tricuspid and 70
patients with BAV undergoing surgery for aortic stenosis (aorta diameter <=45 mm:
BAVnon-dil or >45 mm: BAVdil). Expression changes of the TGF-beta1 active dimer
and ENG were analyzed also by Western blot in ascending aorta samples from other
10 tricuspid aortic valve, 10 BAVnon-dil, and 10 BAVdil patients. The serum
concentration of study targets was assessed through ELISA and the ratio of serum
TGF-beta1/ENG (T/E) was evaluated. All BAVnon-dil patients underwent follow-up
echocardiography to assess aortic growth rate. In BAVnon-dil patients, TGF-beta1
and MMP-2 gene expression increased significantly, whereas MMP-14 and ENG
expression decreased versus controls. Expression changes were confirmed at
protein level for TGF-beta1 and ENG. TGF-beta1 serum concentration significantly
decreased in tricuspid aortic valve and BAVnon-dil patients versus healthy
subjects. ENG serum concentration decreased in all patients, more markedly in
BAVdil. A significant increase of the T/E ratio versus healthy subjects was
unique of patients with BAV. In BAVnon-dil patients, a T/E >=9 was independently
associated in multivariable analysis with higher MMP-2 and lower superoxide
dismutase 3 gene expression, independent of age and aortic diameter. A
significant correlation was observed between baseline T/E ratio and aortic
diameter growth rate in BAVnon-dil patients (r=0.66, P<0.001). CONCLUSIONS: The
novel evidence of a possible value of the T/E ratio as a biomarker of BAV
aortopathy was presented: further validation studies are warranted.
PMID- 28420671
TI - PTK7 localization and protein stability is affected by canonical Wnt ligands.
AB - Protein tyrosine kinase 7 (PTK7) is an evolutionarily conserved transmembrane
receptor with important roles in embryonic development and disease. Originally
identified as a gene upregulated in colon cancer, it was later shown to regulate
planar cell polarity (PCP) and directional cell movement. PTK7 is a Wnt co
receptor; however, its role in Wnt signaling remains controversial. Here, we find
evidence that places PTK7 at the intersection of canonical and non-canonical Wnt
signaling pathways. In presence of canonical Wnt ligands PTK7 is subject to
caveolin-mediated endocytosis, while it is unaffected by non-canonical Wnt
ligands. PTK7 endocytosis is dependent on the presence of the PTK7 co-receptor
Fz7 (also known as Fzd7) and results in lysosomal degradation of PTK7. As we
previously observed that PTK7 activates non-canonical PCP Wnt signaling but
inhibits canonical Wnt signaling, our data suggest a mutual inhibition of
canonical and PTK7 Wnt signaling. PTK7 likely suppresses canonical Wnt signaling
by binding canonical Wnt ligands thereby preventing their interaction with Wnt
receptors that would otherwise support canonical Wnt signaling. Conversely, if
canonical Wnt proteins interact with the PTK7 receptor, they induce its
internalization and degradation.
PMID- 28420672
TI - 3D motion of vesicles along microtubules helps them to circumvent obstacles in
cells.
AB - Vesicle transport is regulated at multiple levels, including regulation by
scaffolding proteins and the cytoskeleton. This tight regulation is essential,
since slowing or stoppage of transport can cause accumulation of obstacles and
has been linked to diseases. Understanding the mechanisms by which transport is
regulated as well as how motor proteins overcome obstacles can give important
clues as to how these mechanisms break down in disease states. Here, we describe
that the cytoskeleton architecture impacts transport in a vesicle-size-dependent
manner, leading to pausing of vesicles larger than the separation of the
microtubules. We further develop methods capable of following 3D transport
processes in living cells. Using these methods, we show that vesicles move using
two different modes along the microtubule. Off-axis motion, which leads to
repositioning of the vesicle in 3D along the microtubule, correlates with the
presence of steric obstacles and may help in circumventing them.
PMID- 28420673
TI - A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent
Hypoglycemia in Patients With Type 1 Diabetes.
AB - High-intensity interval training (HIIT) has gained increasing popularity in
patients with diabetes. HIIT acutely increases plasma lactate levels. This may be
important, since the administration of lactate during hypoglycemia suppresses
symptoms and counterregulation while preserving cognitive function. We tested the
hypothesis that, in the short term, HIIT reduces awareness of hypoglycemia and
attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover
trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH),
patients with impaired awareness of hypoglycemia (IAH), and healthy participants
(n = 10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp,
either after a HIIT session or after seated rest. Compared with rest, HIIT
reduced symptoms of hypoglycemia in patients with NAH but not in healthy
participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive
dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT
suppressed cortisol and growth hormone responses, but not catecholamine responses
to hypoglycemia. The present findings demonstrate that a single HIIT session
rapidly reduces awareness of subsequent hypoglycemia in patients with type 1
diabetes and NAH, but does not in patients with IAH, and attenuates hypoglycemia
induced cognitive dysfunction. The role of exercise-induced lactate in mediating
these effects, potentially serving as an alternative fuel for the brain, should
be further explored.
PMID- 28420674
TI - Indian surgeons call for end to unnecessary operations in private sector.
PMID- 28420676
TI - The association between etanercept serum concentration and psoriasis severity is
highly age-dependent.
AB - The association between etanercept serum concentration and psoriasis disease
severity is poorly investigated, and currently etanercept serum concentration
monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In
this prospective study, we investigated the relation between etanercept exposure
and disease severity via measuring etanercept concentrations at five consecutive
time points in 56 psoriasis patients. Disease severity assessments included the
Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician
Global Assessment (PGA), and etanercept and anti-etanercept antibody
concentrations were determined every 3 months for a period of 1 year. The present
study demonstrated that the association between etanercept concentration and
psoriasis severity is age-dependent: when patients were stratified into three
groups, patients in the youngest age group (-50 years) showed a lower PASI at a
higher etanercept concentration (beta = -0.26), whereas patients in the oldest
age group (+59 years) showed the opposite trend (beta =0.22). Similar age effects
were observed in the relation of etanercept concentration with BSA (P=0.02) and
PGA (P=0.02). The influence of age and length of time in therapy on the
etanercept concentration-disease severity relation was unaffected by body mass
index (BMI) or any other possible confounder. Incidence of anti-etanercept
antibodies was low (2%). The age-dependent relation between etanercept serum
concentrations is both unexpected and intriguing and needs further investigation.
PMID- 28420675
TI - Integrative analysis unveils new functions for the Drosophila Cutoff protein in
noncoding RNA biogenesis and gene regulation.
AB - Piwi-interacting RNAs (piRNAs) are central components of the piRNA pathway, which
directs transposon silencing and guarantees genome integrity in the germ cells of
several metazoans. In Drosophila, piRNAs are produced from discrete regions of
the genome termed piRNA clusters, whose expression relies on the RDC complex
comprised of the core proteins Rhino, Deadlock, and Cutoff. To date, the RDC
complex has been exclusively implicated in the regulation of the piRNA loci. Here
we further elucidate the function of Cutoff and the RDC complex by performing
genome-wide ChIP-seq and RNA-seq assays in the Drosophila ovaries and analyzing
these data together with other publicly available data sets. In agreement with
previous studies, we confirm that Cutoff is involved in the transcriptional
regulation of piRNA clusters and in the repression of transposable elements in
germ cells. Surprisingly, however, we find that Cutoff is enriched at and affects
the expression of other noncoding RNAs, including spliceosomal RNAs (snRNAs) and
small nucleolar RNAs (snoRNAs). At least in some instances, Cutoff appears to act
at a transcriptional level in concert with Rhino and perhaps Deadlock. Finally,
we show that mutations in Cutoff result in the deregulation of hundreds of
protein-coding genes in germ cells. Our study uncovers a broader function for the
RDC complex in the Drosophila germline development.
PMID- 28420677
TI - Typing and Characterization of Bacteria Using Bottom-up Tandem Mass Spectrometry
Proteomics.
AB - Methods for rapid and reliable microbial identification are essential in modern
healthcare. The ability to detect and correctly identify pathogenic species and
their resistance phenotype is necessary for accurate diagnosis and efficient
treatment of infectious diseases. Bottom-up tandem mass spectrometry (MS)
proteomics enables rapid characterization of large parts of the expressed genes
of microorganisms. However, the generated data are highly fragmented, making
downstream analyses complex. Here we present TCUP, a new computational method for
typing and characterizing bacteria using proteomics data from bottom-up tandem
MS. TCUP compares the generated protein sequence data to reference databases and
automatically finds peptides suitable for characterization of taxonomic
composition and identification of expressed antimicrobial resistance genes. TCUP
was evaluated using several clinically relevant bacterial species (Escherichia
coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae,
Moraxella catarrhalis, and Haemophilus influenzae), using both simulated data
generated by in silico peptide digestion and experimental proteomics data
generated by liquid chromatography-tandem mass spectrometry (MS/MS). The results
showed that TCUP performs correct peptide classifications at rates between 90.3
and 98.5% at the species level. The method was also able to estimate the relative
abundances of individual species in mixed cultures. Furthermore, TCUP could
identify expressed beta-lactamases in an extended spectrum beta-lactamase
producing (ESBL) E. coli strain, even when the strain was cultivated in the
absence of antibiotics. Finally, TCUP is computationally efficient, easy to
integrate in existing bioinformatics workflows, and freely available under an
open source license for both Windows and Linux environments.
PMID- 28420678
TI - Automated analysis of high-content microscopy data with deep learning.
AB - Existing computational pipelines for quantitative analysis of high-content
microscopy data rely on traditional machine learning approaches that fail to
accurately classify more than a single dataset without substantial tuning and
training, requiring extensive analysis. Here, we demonstrate that the application
of deep learning to biological image data can overcome the pitfalls associated
with conventional machine learning classifiers. Using a deep convolutional neural
network (DeepLoc) to analyze yeast cell images, we show improved performance over
traditional approaches in the automated classification of protein subcellular
localization. We also demonstrate the ability of DeepLoc to classify highly
divergent image sets, including images of pheromone-arrested cells with abnormal
cellular morphology, as well as images generated in different genetic backgrounds
and in different laboratories. We offer an open-source implementation that
enables updating DeepLoc on new microscopy datasets. This study highlights deep
learning as an important tool for the expedited analysis of high-content
microscopy data.
PMID- 28420679
TI - Tumor Microenvironment Targeting and Responsive Peptide-Based Nanoformulations
for Improved Tumor Therapy.
AB - The tumor microenvironment participates in all stages of tumor progression and
has emerged as a promising therapeutic target for cancer therapy. Rapid progress
in the field of molecular self-assembly using various biologic molecules has
resulted in the fabrication of nanoformulations that specifically target and
regulate microenvironment components to inhibit tumor growth. This inhibition
process is based on differentiating between biophysicochemical cues guiding tumor
and normal tissue microenvironments. Peptides and peptide derivatives, owing to
their biocompatibility, chemical versatility, bioactivity, environmental
sensitivity, and biologic recognition abilities, have been widely used as
building blocks to construct multifunctional nanostructures for targeted drug
delivery and controlled release. Several groups of peptides have been identified
as having the ability to penetrate plasma membranes, regulate the essential
signaling pathways of angiogenesis and immune reactions, and recognize key
components in the tumor microenvironment (such as vascular systems, stromal
cells, and abnormal tumor biophysicochemical features). Thus, using different
modules, various functional peptides, and their derivatives can be integrated
into nanoformulations specifically targeting the tumor microenvironment with
increased selectivity, on-demand response, elevated cellular uptake, and improved
tumor therapy. In this review, we introduce several groups of functional peptides
and highlight peptide-based nanoformulations that specifically target the tumor
microenvironment. We also provide our perspective on the development of smart
drug-delivery systems with enhanced therapeutic efficacy.
PMID- 28420681
TI - Mumps in a 27-year-old man.
PMID- 28420680
TI - Use of azithromycin and risk of ventricular arrhythmia.
AB - BACKGROUND: There are conflicting findings from observational studies of the
arrhythrogenic potential of azithromycin. Our aim was to quantify the association
between azithromycin use and the risk of ventricular arrhythmia. METHODS: We
conducted a nested case-control study within a cohort of new antibiotic users
identified from a network of 7 population-based health care databases in Denmark,
Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010.
Up to 100 controls per case were selected and matched by age, sex and database.
Recency of antibiotic use and type of drug (azithromycin was the exposure of
interest) at the index date (occurrence of ventricular arrhythmia) were
identified. We estimated the odds of ventricular arrhythmia associated with
current azithromycin use relative to current amoxicillin use or nonuse of
antibiotics (>= 365 d without antibiotic exposure) using conditional logistic
regression, adjusting for confounders. RESULTS: We identified 14 040 688 new
antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed
in 12 874, of whom 30 were current azithromycin users. The mean age of the cases
and controls was 63 years, and two-thirds were male. In the pooled data analyses
across databases, azithromycin use was associated with an increased risk of
ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio
[OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk
disappeared when current amoxicillin use was the comparator (adjusted OR 0.90,
95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed
results from the pooled data analysis. INTERPRETATION: Current azithromycin use
was associated with an increased risk of ventricular arrhythmia when compared
with nonuse of antibiotics, but not when compared with current amoxicillin use.
The decreased risk with an active comparator suggests significant confounding by
indication.
PMID- 28420682
TI - Bamboo nodes of the vocal cords.
PMID- 28420683
TI - Hot bodies; Cold War: the forgotten history of breast thermography.
PMID- 28420684
TI - Snowfall and myocardial infarction. What is the effect of barometric pressure?
PMID- 28420685
TI - Response to: "Snowfall and myocardial infarction. What is the effect of
barometric pressure?"
PMID- 28420686
TI - Canada wins legal battle to set patent rules.
PMID- 28420687
TI - Home visits to frail elderly can save money and angst.
PMID- 28420688
TI - Can a partnership between general practitioners and ambulance services reduce
conveyance to emergency care?
AB - BACKGROUND: Emergency services are facing increasing workload pressures, and new
models of care are needed. We evaluate the impact of a service development
involving a partnership between emergency ambulance crews and general
practitioners (GPs) on reducing conveyance rates to the Hospital Emergency
Department(ED) . METHODS: The service model was implemented in the West Midlands
of England. Call handlers identified patients with needs that could be addressed
by a GP using locally agreed criteria. GPs supported the assessment of such
patients either at scene or by telephone. Routine data were collected from
October 2012 to November 2013, from the ambulance service computer-aided dispatch
system. Logistic regression models were used to determine the likelihood for
patients being transported to ED. RESULTS: Of 23 395 emergency contacts during
the evaluation period, 1903 (8.1 %) patients were triaged to GP supported
assessment. Mean age (SD) was 61.8 (27.9) years; 42.9 % were aged 75 years and
over. 1221 (64.2%) had face-to-face GP assessment and 682 (35.8%) via telephone.
1500 (78%) of those who received GP support were not transported to hospital.
After controlling for confounders, those aged greater than 75 years (OR 0.67; 95%
CI 0.52 to 0.86), and females (OR 0.64; 95% CI 0.51 to 0.82) were less likely to
be transported, while those who received GP telephone input rather than face-to
face assessment were more likely to be transferred to an ED (OR 2.14; 95% CI 1.69
to 2.72). CONCLUSION: Support of the paramedic service by GPs enabled patients to
avoid transfer to an ED, potentially avoiding subsequent hospital admission,
reducing costs and improving quality of care for patients that are not in need of
hospital services. However, use of services in the days following the call was
not assessed, and hence the overall impact and safety requires further
evaluation.
PMID- 28420689
TI - 'The year of first aid': effectiveness of a 3-day first aid programme for 7-14
year-old primary school children.
AB - AIM OF THE STUDY: Bystanders can play an important role in the event of sudden
injury or illness. Our aim was to evaluate the effects of a 3-day first aid
course for all primary school age groups (7-14 years old). METHODS: 582 school
children were involved in the study. Training consisted of three sessions with
transfer of theoretical knowledge and practical skills about first aid. The
following most urgent situations were addressed in our study: adult basic life
support (BLS), using an automated external defibrillator (AED), handling an
unconscious patient, managing bleeding and calling the ambulance. Data collection
was made with a questionnaire developed for the study and observation. Students
were tested before, immediately after and 4 months after training. Results were
considered significant in case of p<0.05. RESULTS: Prior to training there was a
low level of knowledge and skills on BLS, management of the unconscious patient,
use of an AED and management of bleeding. Knowledge and skills improved
significantly in all of these categories (p<0.01) and remained significantly
higher than the pre-test level at 4 months after training (p<0.01). Younger
children overall performed less well than older children, but significantly
improved over the pre-test level both immediately and 4 months after training
(p<0.01). Prior first aid training was associated with knowledge of the correct
ambulance number (p=0.015) and management of bleeding (p=0.041). Prior to
training, age was associated with pre-test knowledge and skills of all topics
(p<0.01); after training, it was only associated with AED use (p<0.001). There
was a significant correlation between the depth of chest compression and
children's age, weight, height and body mass index (p<0.001). Ventilation
depended on the same factors (p<0.001). CONCLUSION: Children aged 7-14 years are
able to perform basic life-saving skills. Knowledge retention after 4 months is
good for skills, but thinking in algorithms is difficult for these children.
PMID- 28420690
TI - Identification of protein features encoded by alternative exons using Exon
Ontology.
AB - Transcriptomic genome-wide analyses demonstrate massive variation of alternative
splicing in many physiological and pathological situations. One major challenge
is now to establish the biological contribution of alternative splicing variation
in physiological- or pathological-associated cellular phenotypes. Toward this
end, we developed a computational approach, named "Exon Ontology," based on terms
corresponding to well-characterized protein features organized in an ontology
tree. Exon Ontology is conceptually similar to Gene Ontology-based approaches but
focuses on exon-encoded protein features instead of gene level functional
annotations. Exon Ontology describes the protein features encoded by a selected
list of exons and looks for potential Exon Ontology term enrichment. By applying
this strategy to exons that are differentially spliced between epithelial and
mesenchymal cells and after extensive experimental validation, we demonstrate
that Exon Ontology provides support to discover specific protein features
regulated by alternative splicing. We also show that Exon Ontology helps to
unravel biological processes that depend on suites of coregulated alternative
exons, as we uncovered a role of epithelial cell-enriched splicing factors in the
AKT signaling pathway and of mesenchymal cell-enriched splicing factors in
driving splicing events impacting on autophagy. Freely available on the web, Exon
Ontology is the first computational resource that allows getting a quick insight
into the protein features encoded by alternative exons and investigating whether
coregulated exons contain the same biological information.
PMID- 28420691
TI - Clustering of Drosophila housekeeping promoters facilitates their expression.
AB - Housekeeping genes of animal genomes cluster in the same chromosomal regions. It
has long been suggested that this organization contributes to their steady
expression across all the tissues of the organism. Here, we show that the
activity of Drosophila housekeeping gene promoters depends on the expression of
their neighbors. By measuring the expression of ~85,000 reporters integrated in
Kc167 cells, we identified the best predictors of expression as chromosomal
contacts with the promoters and terminators of active genes. Surprisingly, the
chromatin composition at the insertion site and the contacts with enhancers were
less informative. These results are substantiated by the existence of genomic
"paradoxical" domains, rich in euchromatic features and enhancers, but where the
reporters are expressed at low level, concomitant with a deficit of interactions
with promoters and terminators. This indicates that the proper function of
housekeeping genes relies not on contacts with long distance enhancers but on
spatial clustering. Overall, our results suggest that spatial proximity between
genes increases their expression and that the linear architecture of the
Drosophila genome contributes to this effect.
PMID- 28420692
TI - An improved assembly and annotation of the allohexaploid wheat genome identifies
complete families of agronomic genes and provides genomic evidence for
chromosomal translocations.
AB - Advances in genome sequencing and assembly technologies are generating many high
quality genome sequences, but assemblies of large, repeat-rich polyploid genomes,
such as that of bread wheat, remain fragmented and incomplete. We have generated
a new wheat whole-genome shotgun sequence assembly using a combination of
optimized data types and an assembly algorithm designed to deal with large and
complex genomes. The new assembly represents >78% of the genome with a scaffold
N50 of 88.8 kb that has a high fidelity to the input data. Our new annotation
combines strand-specific Illumina RNA-seq and Pacific Biosciences (PacBio) full
length cDNAs to identify 104,091 high-confidence protein-coding genes and 10,156
noncoding RNA genes. We confirmed three known and identified one novel genome
rearrangements. Our approach enables the rapid and scalable assembly of wheat
genomes, the identification of structural variants, and the definition of
complete gene models, all powerful resources for trait analysis and breeding of
this key global crop.
PMID- 28420693
TI - Modulation of innate immunity of patients with Alzheimer's disease by omega-3
fatty acids.
AB - The innate immune system of patients with Alzheimer's disease and mild cognitive
impairment (MCI) is deregulated with highly increased or decreased transcription
of inflammatory genes and consistently depressed phagocytosis of amyloid-beta1-42
(Abeta) by monocytes and macrophages. Current immune therapies target single
mechanisms in the adaptive immune system but not innate immunity. Here, we
summarize recent advances in therapy by omega-3, omega-6, and epoxy fatty acids;
specialized proresolving mediators; and vitamin D3 that have proven immune
effects and emerging cognitive effects in patients with MCI. The hypothesis of
this approach is that macrophages of normal participants, but not those of
patients with Alzheimer's disease and MCI, possess effective phagocytosis for
Abeta and protect homeostasis of the brain and, furthermore, that defective MCI
macrophages recover phagocytic function via omega-3. Recent studies of fish
derived omega-3 supplementation in patients with MCI have shown polarization of
Apoepsilon3/epsilon3 patients' macrophages to an intermediate M1-M2 phenotype
that is optimal for Abeta phagocytosis and the stabilization of cognitive
decline. Therefore, accumulating preclinical and preliminary clinical evidence
indicates that omega-3 supplementation should be tested in a randomized
controlled clinical trial and that the analysis should involve the apolipoprotein
E genotype and intervening conditions during trial.-Fiala, M., Kooij, G., Wagner,
K., Hammock, B., Pellegrini, M. Modulation of innate immunity of patients with
Alzheimer's disease by omega-3 fatty acids.
PMID- 28420695
TI - Adeno-associated virus 9-mediated Cdk5 inhibitory peptide reverses pathologic
changes and behavioral deficits in the Alzheimer's disease mouse model.
AB - Cyclin-dependent kinase 5 (Cdk5), which binds to and is activated by p35,
phosphorylates multiple substrates and plays an essential role in the development
and function of the CNS; however, proteolytic production of p25 from p35 under
stress conditions leads to the inappropriate activation of Cdk5 and contributes
to hyperphosphorylation of tau and other substrates that are related to the
pathogenesis of Alzheimer's disease. Selective inhibition of aberrant Cdk5
activity via genetic overexpression of Cdk5 inhibitory peptide (CIP) reduces
pathologic changes and prevents brain atrophy and memory loss in p25-transgenic
mice. In the present study, we delivered adeno-associated virus 9 carrying green
fluorescent protein-CIP (AAV9-GFP-CIP) to brain cells via intracerebroventricular
infusion in amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic 3
mo-old mice after the occurrence of beta-amyloid (Abeta) aggregation and the
hyperphosphorylation of tau. Three months of treatment of AAV9-GFP-CIP reduced
pathologic changes, including tau hyperphosphorylation, (Abeta) deposit,
astrocytosis, and microgliosis, which were correlated with the reversal of memory
loss and anxiety-like behavior observed in APP/PS1 mice. The neuroprotection
effect of AAV9-GFP-CIP lasted an additional 7 mo-the end point of the study.
These findings provide a novel strategy to selectively target Cdk5 for the
treatment of Alzheimer's disease.-He, Y., Pan, S., Xu, M., He, R., Huang, W.,
Song, P., Huang, J., Zhang, H.-T., Hu, Y. Adeno-associated virus 9-mediated Cdk5
inhibitory peptide reverses pathologic changes and behavioral deficits in the
Alzheimer's disease mouse model.
PMID- 28420694
TI - Caffeine preferentially protects against oxygen-induced retinopathy.
AB - Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but
current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and
brain development of preterm infants. The clinical observation of reduced ROP
severity in premature infants after caffeine treatment for apnea suggests that
caffeine may protect against ROP. Here, we demonstrate that caffeine did not
interfere with normal retinal vascularization development but selectively
protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine
attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia
induced vaso-obliteration, which suggests a novel protection window by caffeine.
At the hyperoxic phase, caffeine reduced oxygen-induced neural apoptosis by
adenosine A2A receptor (A2AR)-dependent mechanism, as revealed by combined
caffeine and A2AR-knockout treatment. At the hypoxic phase, caffeine reduced
microglial activation and enhanced tip cell formation by A2AR-dependent and
independent mechanisms, as combined caffeine and A2AR knockout produced additive
and nearly full protection against OIR. Together with clinical use of caffeine in
neonates, our demonstration of the selective protection against OIR, effective
therapeutic window, adenosine receptor mechanisms, and neuroglial involvement
provide the direct evidence of the novel effects of caffeine therapy in the
prevention and treatment of ROP.-Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y.,
Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L.,
Chen, J.-F. Caffeine preferentially protects against oxygen-induced retinopathy.
PMID- 28420696
TI - Erratum. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin
Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide
Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The
LixiLan-O Randomized Trial. Diabetes Care 2016;39:2026-2035.
PMID- 28420697
TI - Erratum. Sitagliptin Attenuates the Progression of Carotid Intima-Media
Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin
Preventive Study of Intima-Media Thickness Evaluation (SPIKE). A Randomized
Controlled Trial. Diabetes Care 2016;39:455-464.
PMID- 28420698
TI - Erratum. Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist
LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies.
Diabetes Care 2016;39:1241-1249.
PMID- 28420699
TI - Erratum. Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression
of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of
Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Diabetes
Care 2016;39:139-148.
PMID- 28420700
TI - Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and
Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear
Factor 1B (HNF1B) Molecular Defects.
AB - OBJECTIVE: Molecular defects of hepatocyte nuclear factor 1B (HNF1B) are
associated with a multiorgan disease, including diabetes (maturity-onset diabetes
of the young 5) and kidney abnormalities. The HNF1B syndrome is related to HNF1B
mutations or to a 17q12 deletion spanning 15 genes, including HNF1B. Here, we
described HNF1B-related diabetes and associated phenotypes and assessed
genotype/phenotype correlations at diagnosis and in the long-term. RESEARCH
DESIGN AND METHODS: This multicenter retrospective cohort study included 201
patients, aged 18 years or older at follow-up, with HNF1B mutations (n = 101) or
deletion (n = 100). RESULTS: Diabetes was present in 159 patients. At diagnosis,
clinical symptoms of diabetes were present in 67 of 144 patients and HNF1B renal
disease in 64 of 102. Although responsiveness to sulfonylureas/repaglinide was
observed in 29 of the 51 tested, 111 of 140 patients (79%) were treated with
insulin at follow-up. Diabetic retinopathy and/or neuropathy were present in 46
of 114 patients. Renal cysts were present in 122 of 166 patients, chronic kidney
disease stages 3-4 (CKD3-4) in 75 of 169 (44%), and end-stage renal disease
(ESRD) in 36 of 169 (21%). Compared with the patients with mutations, those with
HNF1B deletion less often had CKD3-4/ESRD at diagnosis (11 of 43 vs. 27 of 35, P
< 10-4) and in the long term (40 of 78 vs. 71 of 91, P = 0.0003). They were
leaner and more frequently treated with insulin. CONCLUSIONS: In patients with
HNF1B syndrome, diabetes complications, cardiovascular risk factors, CKD3-4, and
ESRD are highly prevalent. At diabetes diagnosis, the presence of morphological
and/or functional kidney disease may help etiological diagnosis.
Genotype/phenotype correlations may have implications for the care and the
prognosis of these patients.
PMID- 28420701
TI - Work of breathing and sleep pattern behavior in COPD. How much oxygen or high
flow nasal cannula?
PMID- 28420702
TI - Muscle damage: Scientific fundamentals.
PMID- 28420703
TI - Corrigendum.
PMID- 28420704
TI - Influence of HDL particles on cell-cholesterol efflux under various pathological
conditions.
AB - It has been reported that low cell-cholesterol efflux capacity (CEC) of HDL is an
independent risk factor for CVD. To better understand CEC regulation, we measured
ABCA1- and scavenger receptor class B type I (SR-BI)-dependent cell-cholesterol
efflux, HDL anti-oxidative capacity, HDL particles, lipids, and inflammatory- and
oxidative-stress markers in 122 subjects with elevated plasma levels of
triglyceride (TG), serum amyloid A (SAA), fibrinogen, myeloperoxidase (MPO), or
beta-sitosterol and in 146 controls. In controls, there were strong positive
correlations between ABCA1-dependent cholesterol efflux and small prebeta-1
concentrations (R2 = 0.317) and SR-BI-dependent cholesterol efflux and large
(alpha-1 + alpha-2) HDL particle concentrations (R2 = 0.774). In high-TG
patients, both the concentration and the functionality (prebeta-1 concentration
normalized ABCA1 efflux) of prebeta-1 particles were significantly elevated
compared with controls; however, though the concentration of large particles was
significantly decreased, their functionality (large HDL concentration-normalized
SR-BI efflux) was significantly elevated. High levels of SAA or MPO were not
associated with decreased functionality of either the small (prebeta-1) or the
large (alpha-1 + alpha-2) HDL particles. HDL anti-oxidative capacity was
negatively influenced by high plasma beta-sitosterol levels, but not by the
concentrations of HDL particles, TG, SAA, fibrinogen, or MPO. Our data
demonstrate that under certain conditions CEC is influenced not only by
quantitative (concentration), but also by qualitative (functional) properties of
HDL particles.
PMID- 28420705
TI - Synthesis of neutral ether lipid monoalkyl-diacylglycerol by lipid
acyltransferases.
AB - In mammals, ether lipids exert a wide spectrum of signaling and structural
functions, such as stimulation of immune responses, anti-tumor activities, and
enhancement of sperm functions. Abnormal accumulation of monoalkyl-diacylglycerol
(MADAG) was found in Wolman's disease, a human genetic disorder defined by a
deficiency in lysosomal acid lipase. In the current study, we found that among
the nine recombinant human lipid acyltransferases examined, acyl
CoA:diacylglycerol acyltransferase (DGAT)1, DGAT2, acyl-CoA:monoacylglycerol
acyltransferase (MGAT)2, MGAT3, acyl-CoA:wax-alcohol acyltransferase 2/MFAT, and
DGAT candidate 3 were able to use 1-monoalkylglycerol (1-MAkG) as an acyl
acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG). These enzymes
demonstrated different enzymatic turnover rates and relative efficiencies for the
first and second acylation steps leading to the synthesis of MAMAG and MADAG,
respectively. They also exhibited different degrees of substrate preference when
presented with 1-monooleoylglycerol versus 1-MAkG. In CHO-K1 cells, treatment
with DGAT1 selective inhibitor, XP-620, completely blocked the synthesis of
MADAG, indicating that DGAT1 is the predominant enzyme responsible for the
intracellular synthesis of MADAG in this model system. The levels of MADAG in the
adrenal gland of DGAT1 KO mice were reduced as compared with those of the WT
mice, suggesting that DGAT1 is a major enzyme for the synthesis of MADAG in this
tissue. Our findings indicate that several of these lipid acyltransferases may be
able to synthesize neutral ether lipids in mammals.
PMID- 28420707
TI - Role of the fatty acid-binding protein 4 in heart failure and cardiovascular
disease.
AB - Obesity and ectopic fat accumulation in non-adipose tissues are major
contributors to heart failure (HF) and cardiovascular disease (CVD). Adipocytes
act as endocrine organs by releasing a large number of bioactive molecules into
the bloodstream, which participate in a communication network between white
adipose tissue and other organs, including the heart. Among these molecules,
fatty acid-binding protein 4 (FABP4) has recently been shown to increase
cardiometabolic risk. Both clinical and experimental evidence have identified
FABP4 as a relevant player in atherosclerosis and coronary artery disease, and it
has been directly related to cardiac alterations such as left ventricular
hypertrophy (LVH) and both systolic and diastolic cardiac dysfunction. The
available interventional studies preclude the establishment of a direct causal
role of this molecule in CVD and HF and propose FABP4 as a biomarker rather than
as an aetiological factor. However, several experimental reports have suggested
that FABP4 may act as a direct contributor to cardiac metabolism and
physiopathology, and the pharmacological targeting of FABP4 may restore some of
the metabolic alterations that are conducive to CVD and HF. Here, we review the
current knowledge regarding FABP4 in the context of HF and CVD as well as the
molecular basis by which this protein participates in the regulation of cardiac
function.
PMID- 28420706
TI - Common structural features of cholesterol binding sites in crystallized soluble
proteins.
AB - Cholesterol-protein interactions are essential for the architectural organization
of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in
transmembrane proteins have been identified, little is known about cholesterol
recognition by soluble proteins. We reviewed the structural characteristics of
binding sites for cholesterol and cholesterol sulfate from crystallographic
structures available in the Protein Data Bank. This analysis unveiled key
features of cholesterol-binding sites that are present in either all or the
majority of sites: i) the cholesterol molecule is generally positioned between
protein domains that have an organized secondary structure; ii) the cholesterol
hydroxyl/sulfo group is often partnered by Asn, Gln, and/or Tyr, while the
hydrophobic part of cholesterol interacts with Leu, Ile, Val, and/or Phe; iii)
cholesterol hydrogen-bonding partners are often found on alpha-helices, while
amino acids that interact with cholesterol's hydrophobic core have a slight
preference for beta-strands and secondary structure-lacking protein areas; iv)
the steroid's C21 and C26 constitute the "hot spots" most often seen for steroid
protein hydrophobic interactions; v) common "cold spots" are C8-C10, C13, and
C17, at which contacts with the proteins were not detected. Several common
features we identified for soluble protein-steroid interaction appear
evolutionarily conserved.
PMID- 28420708
TI - Activation of the P2Y2 receptor regulates bone cell function by enhancing ATP
release.
AB - Bone cells constitutively release ATP into the extracellular environment where it
acts locally via P2 receptors to regulate bone cell function. Whilst P2Y2
receptor stimulation regulates bone mineralisation, the functional effects of
this receptor in osteoclasts remain unknown. This investigation used the P2Y2
receptor knockout (P2Y2R-/- ) mouse model to investigate the role of this
receptor in bone. MicroCT analysis of P2Y2R-/- mice demonstrated age-related
increases in trabecular bone volume (<=48%), number (<=30%) and thickness
(<=17%). In vitro P2Y2R-/- osteoblasts displayed a 3-fold increase in bone
formation and alkaline phosphatase activity, whilst P2Y2R-/- osteoclasts
exhibited a 65% reduction in resorptive activity. Serum cross-linked C
telopeptide levels (CTX, resorption marker) were also decreased (<=35%). The
resorption defect in P2Y2R-/- osteoclasts was rescued by the addition of
exogenous ATP, suggesting that an ATP deficit could be a key factor in the
reduced function of these cells. In agreement, we found that basal ATP release
was reduced up to 53% in P2Y2R-/- osteoclasts. The P2Y2 receptor agonists, UTP
and 2-thioUTP, increased osteoclast activity and ATP release in wild-type but not
in P2Y2R-/- cells. This indicates that the P2Y2 receptor may regulate osteoclast
function indirectly by promoting ATP release. UTP and 2-thioUTP also stimulate
ATP release from osteoblasts suggesting that the P2Y2 receptor exerts a similar
function in these cells. Taken together, our findings are consistent with the
notion that the primary action of P2Y2 receptor signalling in bone is to regulate
extracellular ATP levels.
PMID- 28420709
TI - Thermal imprinting modifies adult stress and innate immune responsiveness in the
teleost sea bream.
AB - The impact of thermal imprinting on the plasticity of the hypothalamic-pituitary
interrenal (HPI) axis and stress response in an adult ectotherm, the gilthead sea
bream (Sparusaurata, L.), during its development was assessed. Fish were reared
under 4 thermal regimes, and the resulting adults exposed to acute confinement
stress and plasma cortisol levels and genes of the HPI axis were monitored.
Changes in immune function, a common result of stress, were also evaluated using
histomorphometric measurements of melanomacrophages centers (MMCs) in the head
kidney and by monitoring macrophage-related transcripts. Thermal history
significantly modified the HPI responsiveness in adult sea bream when eggs and
larvae were reared at a higher than optimal temperature (HT, 22 degrees C), and
they had a reduced amplitude in their cortisol response and significantly
upregulated pituitary pomc and head kidney star transcripts. Additionally, after
an acute stress challenge, immune function was modified and the head kidney of
adult fish reared during development at high temperatures (HT and LHT, 18-22
degrees C) had a decreased number of MMCs and a significant downregulation of
dopachrome tautomerase. Thermal imprinting during development influenced adult
sea bream physiology and increased plasma levels of glucose and sodium even in
the absence of an acute stress in fish reared under a high-low thermal regime
(HLT, 22-18 degrees C). Overall, the results demonstrate that temperature during
early development influences the adult HPI axis and immune function in a teleost
fish.
PMID- 28420710
TI - Reciprocal proteasome-mediated degradation of PIFs and HFR1 underlies
photomorphogenic development in Arabidopsis.
AB - The phytochrome-mediated regulation of photomorphogenesis under red and far-red
light conditions involves both positively and negatively acting factors. The
positively acting factors (e.g. HY5/HFR1/LAF1 and others) are degraded in the
dark to prevent photomorphogenesis. By contrast, the negatively acting factors
(e.g. phytochrome-interacting factors or PIFs) are degraded in response to light
to promote photomorphogenesis. Here, we show that the negatively acting factor
PIF1 is also degraded in the dark by direct heterodimerization with the
positively acting factor HFR1. Conversely, PIF1 also promotes the degradation of
HFR1 in darkness. PIF1 enhances the poly-ubiquitylation of HFR1 by COP1 in vivo
and in vitro In addition, the reciprocal co-degradation of PIF1 and HFR1 is
dependent on the 26S proteasome pathway in vivo Genetic evidence shows that the
hfr1 mutant partially suppresses the constitutive photomorphogenic phenotypes of
cop1-6 pif1 and of the quadruple mutant pifq both in the dark and in far-red
light conditions. Taken together, these data uncover a co-degradation mechanism
between PIFs and HFR1 that underlies photomorphogenic development in Arabidopsis
thaliana.
PMID- 28420711
TI - Excitatory neurons sculpt GABAergic neuronal connectivity in the C. elegans motor
circuit.
AB - Establishing and maintaining the appropriate number of GABA synapses is key for
balancing excitation and inhibition in the nervous system, though we have only a
limited understanding of the mechanisms controlling GABA circuit connectivity.
Here, we show that disrupting cholinergic innervation of GABAergic neurons in the
C. elegans motor circuit alters GABAergic neuron synaptic connectivity. These
changes are accompanied by reduced frequency and increased amplitude of GABAergic
synaptic events. Acute genetic disruption in early development, during the
integration of post-embryonic-born GABAergic neurons into the circuit, produces
irreversible effects on GABAergic synaptic connectivity that mimic those produced
by chronic manipulations. In contrast, acute genetic disruption of cholinergic
signaling in the adult circuit does not reproduce these effects. Our findings
reveal that GABAergic signaling is regulated by cholinergic neuronal activity,
probably through distinct mechanisms in the developing and mature nervous system.
PMID- 28420712
TI - Sec71 functions as a GEF for the small GTPase Arf1 to govern dendrite pruning of
Drosophila sensory neurons.
AB - Pruning, whereby neurons eliminate their excess neurites, is central for the
maturation of the nervous system. In Drosophila, sensory neurons, ddaCs,
selectively prune their larval dendrites without affecting their axons during
metamorphosis. However, it is unknown whether the secretory pathway plays a role
in dendrite pruning. Here, we show that the small GTPase Arf1, an important
regulator of the secretory pathway, is specifically required for dendrite pruning
of ddaC/D/E sensory neurons but dispensable for apoptosis of ddaF neurons.
Analyses of the GTP- and GDP-locked forms of Arf1 indicate that the cycling of
Arf1 between GDP-bound and GTP-bound forms is essential for dendrite pruning. We
further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that
preferentially interacts with its GDP-bound form. Like Arf1, Sec71 is also
important for dendrite pruning, but not for apoptosis, of sensory neurons. Arf1
and Sec71 are interdependent for their localizations on Golgi. Finally, we show
that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5
dependent endocytosis to facilitate endocytosis and degradation of the cell
adhesion molecule Neuroglian (Nrg).
PMID- 28420713
TI - Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA.
AB - The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and
glucose metabolism that plays a critical role in energy homeostasis. The impact
of diet on PKA signaling has not been defined, although perturbations in
individual PKA subunits are associated with changes in adiposity, physical
activity and energy intake in mice and humans. We hypothesized that a high fat
diet (HFD) would elicit peripheral and central alterations in the PKA system that
would differ depending on length of exposure to HFD; these differences could
protect against or promote diet-induced obesity (DIO). 12-week-old C57Bl/6J mice
were randomly assigned to a regular diet or HFD and weighed weekly throughout the
feeding studies (4 days, 14 weeks; respectively), and during killing. PKA
activity and subunit expression were measured in liver, gonadal adipose tissue
(AT) and brain. Acute HFD-feeding suppressed basal hepatic PKA activity. In
contrast, hepatic and hypothalamic PKA activities were significantly increased
after chronic HFD-feeding. Changes in AT were more subtle, and overall, altered
PKA regulation in response to chronic HFD exposure was more profound in female
mice. The suppression of hepatic PKA activity after 4 day HFD-feeding was
indicative of a protective peripheral effect against obesity in the context of
overnutrition. In response to chronic HFD-feeding, and with the development of
DIO, dysregulated hepatic and hypothalamic PKA signaling was a signature of
obesity that is likely to promote further metabolic dysfunction in mice.
PMID- 28420715
TI - Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic
nephropathy.
AB - Diabetic nephropathy is one of the most frequent, devastating and costly
complications of diabetes. The available therapeutic approaches are limited.
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose
lowering drugs that might also have reno-protective properties. DPP-4 exists in
two forms: a plasma membrane-bound form and a soluble form, and can exert many
biological actions mainly through its peptidase activity and interaction with
extracellular matrix components. The kidneys have the highest DPP-4 expression
level in mammalians. DPP-4 expression and urinary activity are up-regulated in
diabetic nephropathy, highlighting its role as a potential target to manage
diabetic nephropathy. Preclinical animal studies and some clinical data suggest
that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood
pressure- and glucose-independent manner. Many studies reported that these reno
protective effects could be due to increased half-life of DPP-4 substrates such
as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a).
However, the underlying mechanisms are far from being completely understood and
clearly need further investigations.
PMID- 28420714
TI - Pancreatic islet inflammation: an emerging role for chemokines.
AB - Both type 1 and type 2 diabetes exhibit features of inflammation associated with
alterations in pancreatic islet function and mass. These immunological
disruptions, if unresolved, contribute to the overall pathogenesis of disease
onset. This review presents the emerging role of pancreatic islet chemokine
production as a critical factor regulating immune cell entry into pancreatic
tissue as well as an important facilitator of changes in tissue resident
leukocyte activity. Signaling through two specific chemokine receptors (i.e.,
CXCR2 and CXCR3) is presented to illustrate key points regarding ligand-mediated
regulation of innate and adaptive immune cell responses. The prospective roles of
chemokine ligands and their corresponding chemokine receptors to influence the
onset and progression of autoimmune- and obesity-associated forms of diabetes are
discussed.
PMID- 28420716
TI - A MEN1 pancreatic neuroendocrine tumour mouse model under temporal control.
AB - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder
characterised by occurrence of parathyroid tumours and neuroendocrine tumours
(NETs) of the pancreatic islets and anterior pituitary. The MEN1 gene, encoding
menin, is a tumour suppressor, but its precise role in initiating in vivo
tumourigenesis remains to be elucidated. The availability of a temporally
controlled conditional MEN1 mouse model would greatly facilitate the study of
such early tumourigenic events, and overcome the limitations of other MEN1
knockout models, in which menin is lost from conception or tumour development
occurs asynchronously. To generate a temporally controlled conditional mouse
model, we crossbred mice with the MEN1 gene floxed by LoxP sites (Men1L/L ), and
mice expressing tamoxifen-inducible Cre recombinase under the control of the rat
insulin promoter (RIP2-CreER), to establish a pancreatic beta-cell-specific NET
model under temporal control (Men1L/L /RIP2-CreER). Men1L/L /RIP2-CreER mice aged
~3 months were given tamoxifen in the diet for 5 days, and pancreata harvested 2
2.5, 2.9-3.5 and 4.5-5.5 months later. Control mice did not express Cre and did
not receive tamoxifen. Immunostaining of pancreata from tamoxifen-treated Men1L/L
/RIP2-CreER mice, compared to control mice, showed at all ages: loss of menin in
all islets; increased islet area (>4.2-fold); increased proliferation of insulin
immunostaining beta-cells (>2.3-fold) and decreased proliferation of glucagon
immunostaining alpha-cells (>1.7-fold). There were no gender and apoptotic or
proliferation differences, and extra-pancreatic tumours were not detected. Thus,
we have established a mouse model (Men1L/L /RIP2-CreER) to study early events in
the development of pancreatic beta-cell NETs.
PMID- 28420717
TI - Heart, lipids and hormones.
AB - Cardiovascular disease is the leading cause of death in general population.
Besides well-known risk factors such as hypertension, impaired glucose tolerance
and dyslipidemia, growing evidence suggests that hormonal changes in various
endocrine diseases also impact the cardiac morphology and function. Recent
studies highlight the importance of ectopic intracellular myocardial and
pericardial lipid deposition, since even slight changes of these fat depots are
associated with alterations in cardiac performance. In this review, we overview
the effects of hormones, including insulin, thyroid hormones, growth hormone and
cortisol, on heart function, focusing on their impact on myocardial lipid
metabolism, cardiac substrate utilization and ectopic lipid deposition, in order
to highlight the important role of even subtle hormonal changes for heart
function in various endocrine and metabolic diseases.
PMID- 28420718
TI - Sex, BMI and age differences in metabolic syndrome: the Dutch Lifelines Cohort
Study.
AB - INTRODUCTION: To evaluate the prevalence of metabolic syndrome (MetS) and its
individual components within sex-, body mass index (BMI)- and age combined
clusters. In addition, we used the age-adjusted blood pressure thresholds to
demonstrate the effect on the prevalence of MetS and elevated blood pressure.
SUBJECTS AND METHODS: Cross-sectional data from 74,531 Western European
participants, aged 18-79 years, were used from the Dutch Lifelines Cohort Study.
MetS was defined according to the revised NCEP-ATPIII. Age-adjusted blood
pressure thresholds were defined as recommended by the eight reports of the Joint
National Committee (>=140/90 mmHg for those aged <60 years, and >=150/90 mmHg for
those aged >=60 years). RESULTS: 19.2% men and 12.1% women had MetS. MetS
prevalence increased with BMI and age. Independent of BMI, abdominal obesity
dominated MetS prevalence especially in women, while elevated blood pressure was
already highly prevalent among young men. Applying age-adjusted blood pressure
thresholds resulted in a 0.2-11.9% prevalence drop in MetS and 6.0-36.3%
prevalence drop in elevated blood pressure, within the combined sex, BMI and age
clusters. CONCLUSIONS: We observed a gender disparity with age and BMI for the
prevalence of MetS and, especially, abdominal obesity and elevated blood
pressure. The strict threshold level for elevated blood pressure in the revised
NCEP-ATPIII, results in an overestimation of MetS prevalence.
PMID- 28420720
TI - A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in
Patients with Advanced Solid Tumors.
AB - Purpose: Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating
the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). This phase
I study investigated the safety, pharmacokinetics, pharmacodynamics, and
antitumor activity of ABC294640, a first-in-class orally available inhibitor of
SK2.Experimental Design: Escalating doses of ABC294640 were administered orally
to patients with advanced solid tumors in sequential cohorts at the following
dose levels: 250 mg qd, 250 mg bid, 500 mg bid, and 750 mg bid, continuously in
cycles of 28 days. Serial blood samples were obtained to measure ABC294640
concentrations and sphingolipid profiles.Results: Twenty-two patients were
enrolled, and 21 received ABC294640. The most common drug-related toxicities were
nausea, vomiting, and fatigue. Among the 4 patients at 750 mg bid, one had dose
limiting grade 3 nausea and vomiting, and 2 were unable to complete cycle 1 due
to diverse drug-related toxicities. The 500 mg bid dose level was established as
the recommended phase II dose. ABC294640 administration resulted in decreases in
S1P levels over the first 12 hours, with return to baseline at 24 hours. The best
response was a partial response in a patient with cholangiocarcinoma at 250 mg
qd, and stable disease was observed in 6 patients with various solid tumors
across dose levels.Conclusions: At 500 mg bid, ABC294640 is well tolerated and
achieves biologically relevant plasma concentrations. Changes in plasma
sphingolipid levels may provide a useful pharmacodynamic biomarker for ABC294640.
Clin Cancer Res; 23(16); 4642-50. (c)2017 AACR.
PMID- 28420721
TI - Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or
Refractory Hematologic Malignancies: A California Cancer Consortium Trial.
AB - Purpose: A phase I study was conducted to determine the MTD, dose-limiting
toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous
emulsion in relapsed/refractory hematologic malignancies.Experimental Design:
Fenretinide (80-1,810 mg/m2/day) was administered by continuous infusion on days
1 to 5, in 21-day cycles, using an accelerated titration design.Results: Twenty
nine patients, treated with a median of three prior regimens (range, 1-7), were
enrolled and received the test drug. Ninety-seven courses were completed. An MTD
was reached at 1,280 mg/m2/day for 5 days. Course 1 DLTs included 6 patients with
hypertriglyceridemia, 4 of whom were asymptomatic; 2 patients experienced DLT
thrombocytopenia (asymptomatic). Of 11 patients with response-evaluable
peripheral T-cell lymphomas, two had complete responses [CR, progression-free
survival (PFS) 68+ months; unconfirmed CR, PFS 14+ months], two had unconfirmed
partial responses (unconfirmed PR, PFS 5 months; unconfirmed PR, PFS 6 months),
and five had stable disease (2-12 cycles). One patient with mature B-cell
lymphoma had an unconfirmed PR sustained for two cycles. Steady-state plasma
levels were approximately 10 mcg/mL (mid-20s MUmol/L) at 640 mg/m2/day,
approximately 14 mcg/mL (mid-30s MUmol/L) at 905 mg/m2/day, and approximately 22
mcg/mL (mid-50s MUmol/L) at 1,280 mg/m2/day.Conclusions: Intravenous fenretinide
obtained significantly higher plasma levels than a previous capsule formulation,
had acceptable toxicities, and evidenced antitumor activity in peripheral T-cell
lymphomas. A recommended phase II dosing is 600 mg/m2 on day 1, followed by 1,200
mg/m2 on days 2 to 5, every 21 days. A registration-enabling phase II study in
relapsed/refractory PTCL (ClinicalTrials.gov identifier: NCT02495415) is ongoing.
Clin Cancer Res; 23(16); 4550-5. (c)2017 AACR.
PMID- 28420722
TI - Low Tumor Mitochondrial DNA Content Is Associated with Better Outcome in Breast
Cancer Patients Receiving Anthracycline-Based Chemotherapy.
AB - Purpose: In this study, we aimed to explore whether low levels of mitochondrial
DNA (mtDNA) content in the primary tumor could predict better outcome for breast
cancer patients receiving anthracycline-based therapies. We hypothesized that
tumor cells with low mtDNA content are more susceptible to mitochondrial damage
induced by anthracyclines, and thus are more susceptible to anthracycline
treatment.Experimental Design: We measured mtDNA content by a qPCR approach in
295 primary breast tumor specimens originating from two well-defined cohorts: 174
lymph node-positive patients who received adjuvant chemotherapy and 121 patients
with advanced disease who received chemotherapy as first-line palliative
treatment. The chemotherapy regimens given were either anthracycline-based
(FAC/FEC) or methotrexate-based (CMF).Results: In both the adjuvant and advanced
settings, we observed increased benefit for patients with low mtDNA content in
their primary tumor, but only when treated with FAC/FEC. In multivariable Cox
regression analysis for respectively distant metastasis-free survival and
progression-free survival, the HR for the FAC/FEC-treated mtDNA low group in the
adjuvant setting was 0.46 [95% confidence interval (CI), 0.24-0.89; P = 0.020]
and in the advanced setting 0.49 (95% CI, 0.27-0.90; P = 0.022) compared with the
FAC/FEC-treated mtDNA high group. We did not observe these associations in the
patients treated with CMF.Conclusions: In our two study cohorts, breast cancer
patients with low mtDNA content in their primary tumor had better outcome from
anthracycline-containing chemotherapy. The frequently observed decrease in mtDNA
content in primary breast tumors may be exploited by guiding chemotherapeutic
regimen decision making. Clin Cancer Res; 23(16); 4735-43. (c)2017 AACR.
PMID- 28420719
TI - Emotional Modulation of Learning and Memory: Pharmacological Implications.
AB - Memory consolidation involves the process by which newly acquired information
becomes stored in a long-lasting fashion. Evidence acquired over the past several
decades, especially from studies using post-training drug administration,
indicates that emotional arousal during the consolidation period influences and
enhances the strength of the memory and that multiple different chemical
signaling systems participate in this process. The mechanisms underlying the
emotional influences on memory involve the release of stress hormones and
activation of the basolateral amygdala, which work together to modulate memory
consolidation. Moreover, work suggests that this amygdala-based memory modulation
occurs with numerous types of learning and involves interactions with many
different brain regions to alter consolidation. Additionally, studies suggest
that emotional arousal and amygdala activity in particular influence synaptic
plasticity and associated proteins in downstream brain regions. This review
considers the historical understanding for memory modulation and cellular
consolidation processes and examines several research areas currently using this
foundational knowledge to develop therapeutic treatments.
PMID- 28420723
TI - Mitochondrial BAX Determines the Predisposition to Apoptosis in Human AML.
AB - Purpose: Cell-to-cell variability in apoptosis signaling contributes to
heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia,
such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit
mammalian cells to apoptosis and are inhibited by retrotranslocation from the
mitochondria into the cytosol. The subcellular localization of BAX and BAK could
determine the cellular predisposition to apoptotic death.Experimental Design: The
relative localization of BAX and BAK was determined by fractionation of AML cell
lines and patient samples of a test cohort and a validation cohort.Results: This
study shows that relative BAX localization determines the predisposition of
different AML cell lines to apoptosis. Human AML displays a surprising variety of
relative BAX localizations. In a test cohort of 48 patients with AML,
mitochondria-shifted BAX correlated with improved patient survival, FLT3-ITD
status, and leukocytosis. Analysis of a validation cohort of 80 elderly patients
treated with myelosuppressive chemotherapy confirmed that relative BAX
localization correlates with probability of disease progression, FLT3-ITD status,
and leukocytosis. Relative BAX localization could therefore be helpful to
identify elderly or frail patients who may benefit from cytotoxic
therapy.Conclusions: In this retrospective analysis of two independent AML
cohorts, our data suggest that Bax localization may predict prognosis of patients
with AML and cellular predisposition to apoptosis, combining the actual
contribution of known and unknown factors to a final "common path." Clin Cancer
Res; 23(16); 4805-16. (c)2017 AACR.
PMID- 28420724
TI - A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated
Cancer Metastasis.
AB - Purpose: Cancer metastasis can occur at the early stage of tumor development when
a primary tumor is at the microscopic size. In particular, the interaction of
malignant cells with other cell types including cancer-associated fibroblasts
(CAF) in promoting metastasis at the early stage of tumor development remains
largely unknown. Here, we investigated the role of CAFs in facilitating the
initial events of cancer metastasis when primary tumors were at microscopic
sizes.Experimental Design: Multicolor-coded cancer cells and CAFs were
coimplanted into the transparent zebrafish body and metastasis at a single-cell
level was monitored in living animals. Healthy fibroblasts, tumor factor-educated
fibroblasts, and CAFs isolated from various tumors were tested for their ability
to facilitate metastasis.Results: We showed that CAFs promoted cancer cell
metastasis at the very early stage during primary tumor development. When a
primary tumor was at the microscopic size consisting of a few hundred cells, CAFs
were able to hijack cancer cells for dissemination from the primary site.
Surprisingly, a majority of metastatic cancer cells remained in tight association
with CAFs in the circulation. Furthermore, stimulation of non-metastasis
promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to
acquisition of their metastatic capacity.Conclusions: Cancer metastasis occurs at
the very early stage of tumor formation consisting of only a few hundred cells.
CAFs are the key cellular determinant for metastasis. Our findings provide novel
mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs
for cancer therapy should be aimed at the early stage during cancer development.
Clin Cancer Res; 23(16); 4769-79. (c)2017 AACR.
PMID- 28420725
TI - Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by
Detecting Circulating Tumor DNA in Urine.
AB - Purpose: Noninvasive drug biomarkers for the early assessment of tumor response
can enable adaptive therapeutic decision-making and proof-of-concept studies for
investigational drugs. Circulating tumor DNA (ctDNA) is released into the
circulation by tumor cell turnover and has been shown to be detectable in
urine.Experimental Design: We tested the hypothesis that dynamic changes in EGFR
activating (exon 19del and L858R) and resistance (T790M) mutation levels detected
in urine could inform tumor response within days of therapy for advanced non
small cell lung cancer (NSCLC) patients receiving osimertinib, a second-line
third-generation anti-EGFR tyrosine kinase inhibitor.Results: Eight of nine
evaluable NSCLC patients had detectable T790M-mutant DNA fragments in
pretreatment baseline samples. Daily monitoring of mutations in urine indicated a
pattern of intermittent spikes throughout week 1, suggesting apoptosis with an
overall decrease in fragment numbers from baselines to day 7 preceding
radiographic response assessed at 6 to 12 weeks.Conclusions: These findings
suggest drug-induced tumor apoptosis within days of initial dosing. Daily
sampling of ctDNA may enable early assessment of patient response and proof-of
concept studies for drug development. The modeling of tumor lysis through the day
to-day kinetics of ctDNA released into the blood and then into the urine is
demonstrated in this proof-of-concept study in lung cancer patients receiving
anti-EGFR tyrosine kinase inhibitors. This strategy may determine the specific
clonal populations of cells which undergo apoptosis within the first week of
therapy. This has important implications for developing combinational strategies
to address inter- and intralesional heterogeneity and characterizing residual
disease after initial drug exposure. Clin Cancer Res; 23(16); 4716-23. (c)2017
AACR.
PMID- 28420726
TI - Intra- and Interobserver Reproducibility Assessment of PD-L1 Biomarker in Non
Small Cell Lung Cancer.
AB - Purpose: Reliable and reproducible methods for identifying PD-L1 expression on
tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested
the reproducibility of the assessment of PD-L1 expression in non-small cell lung
cancer (NSCLC) tissue samples by pathologists.Experimental Design: NSCLC samples
were stained with PD-L1 22C3 pharmDx kit using the Dako Autostainer Link 48
Platform. Two sample sets of 60 samples each were designed to assess inter- and
intraobserver reproducibility considering two cut points for positivity: 1% or
50% of PD-L1 stained tumor cells. A randomization process was used to obtain
equal distribution of PD-L1 positive and negative samples within each sample set.
Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all
samples on two consecutive days. Subgroup 2 performed the same assessments,
except they received a 1-hour training session prior to the second
assessment.Results: For intraobserver reproducibility, the overall percent
agreement (OPA) was 89.7% [95% confidence interval (CI), 85.7-92.6] for the 1%
cut point and 91.3% (95% CI, 87.6-94.0) for the 50% cut point. For interobserver
reproducibility, OPA was 84.2% (95% CI, 82.8-85.5) for the 1% cut point and 81.9%
(95% CI, 80.4-83.3) for the 50% cut point, and Cohen's kappa coefficients were
0.68 (95% CI, 0.65-0.71) and 0.58 (95% CI, 0.55-0.62), respectively. The training
was found to have no or very little impact on intra- or interobserver
reproducibility.Conclusions: Pathologists reported good reproducibility at both
1% and 50% cut points. More adapted training could potentially increase
reliability, in particular for samples with PD-L1 proportion, scores around 50%.
Clin Cancer Res; 23(16); 4569-77. (c)2017 AACR.
PMID- 28420728
TI - A membrane-embedded pathway delivers general anesthetics to two interacting
binding sites in the Gloeobacter violaceus ion channel.
AB - General anesthetics exert their effects on the central nervous system by acting
on ion channels, most notably pentameric ligand-gated ion channels. Although
numerous studies have focused on pentameric ligand-gated ion channels, the
details of anesthetic binding and channel modulation are still debated. A better
understanding of the anesthetic mechanism of action is necessary for the
development of safer and more efficacious drugs. Herein, we present a
computational study identifying two anesthetic binding sites in the transmembrane
domain of the Gloeobacter violaceus ligand-gated ion channel (GLIC) channel,
characterize the putative binding pathway, and observe structural changes
associated with channel function. Molecular simulations of desflurane reveal a
binding pathway to GLIC via a membrane-embedded tunnel using an intrasubunit
protein lumen as the conduit, an observation that explains the Meyer-Overton
hypothesis, or why the lipophilicity of an anesthetic and its potency are
generally proportional. Moreover, employing high concentrations of ligand led to
the identification of a second transmembrane site (TM2) that inhibits
dissociation of anesthetic from the TM1 site and is consistent with the high
concentrations of anesthetics required to achieve clinical effects. Finally,
asymmetric binding patterns of anesthetic to the channel were found to promote an
iris-like conformational change that constricts and dehydrates the ion pore,
creating a 13.5 kcal/mol barrier to ion translocation. Together with previous
studies, the simulations presented herein demonstrate a novel anesthetic binding
site in GLIC that is accessed through a membrane-embedded tunnel and interacts
with a previously known site, resulting in conformational changes that produce a
non-conductive state of the channel.
PMID- 28420729
TI - Factor V has an anticoagulant cofactor activity that targets the early phase of
coagulation.
AB - Tissue factor pathway inhibitor (TFPI), the main inhibitor of initiation of
coagulation, exerts an important anticoagulant role through the factor Xa (FXa)
dependent inhibition of tissue factor/factor VIIa. Protein S is a TFPI cofactor,
enhancing the efficiency of FXa inhibition. TFPI can also inhibit prothrombinase
assembly by directly interacting with coagulation factor V (FV), which has been
activated by FXa. Because full-length TFPI associates with FV in plasma, we
hypothesized that FV may influence TFPI inhibitory function. Using pure component
FXa inhibition assays, we found that although FV alone did not influence TFPI
mediated FXa inhibition, it further enhanced TFPI in the presence of protein S,
resulting in an ~8-fold reduction in Ki compared with TFPI alone. A FV variant
(R709Q/R1018Q/R1545Q, FVDeltaIIa) that cannot be cleaved/activated by thrombin or
FXa also enhanced TFPI-mediated inhibition of FXa ~12-fold in the presence of
protein S. In contrast, neither activated FV nor recombinant B-domain-deleted FV
could enhance TFPI-mediated inhibition of FXa in the presence of protein S,
suggesting a functional contribution of the B domain. Using TFPI and protein S
variants, we show further that the enhancement of TFPI-mediated FXa inhibition by
protein S and FV depends on a direct protein S/TFPI interaction and that the TFPI
C-terminal tail is not essential for this enhancement. In FXa-catalyzed
prothrombin activation assays, both FV and FVDeltaIIa (but not activated FV)
enhanced TFPI function in the presence of protein S. These results demonstrate a
new anticoagulant (cofactor) function of FV that targets the early phase of
coagulation before prothrombinase assembly.
PMID- 28420730
TI - Structure and characterization of a class 3B proline utilization A: Ligand
induced dimerization and importance of the C-terminal domain for catalysis.
AB - The bifunctional flavoenzyme proline utilization A (PutA) catalyzes the two-step
oxidation of proline to glutamate using separate proline dehydrogenase (PRODH)
and l-glutamate-gamma-semialdehyde dehydrogenase active sites. Because PutAs
catalyze sequential reactions, they are good systems for studying how metabolic
enzymes communicate via substrate channeling. Although mechanistically similar,
PutAs vary widely in domain architecture, oligomeric state, and quaternary
structure, and these variations represent different structural solutions to the
problem of sequestering a reactive metabolite. Here, we studied PutA from
Corynebacterium freiburgense (CfPutA), which belongs to the uncharacterized 3B
class of PutAs. A 2.7 A resolution crystal structure showed the canonical
arrangement of PRODH, l-glutamate-gamma-semialdehyde dehydrogenase, and C
terminal domains, including an extended interdomain tunnel associated with
substrate channeling. The structure unexpectedly revealed a novel open
conformation of the PRODH active site, which is interpreted to represent the non
activated conformation, an elusive form of PutA that exhibits suboptimal
channeling. Nevertheless, CfPutA exhibited normal substrate-channeling activity,
indicating that it isomerizes into the active state under assay conditions.
Sedimentation-velocity experiments provided insight into the isomerization
process, showing that CfPutA dimerizes in the presence of a proline analog and
NAD+ These results are consistent with the morpheein model of enzyme hysteresis,
in which substrate binding induces conformational changes that promote assembly
of a high-activity oligomer. Finally, we used domain deletion analysis to
investigate the function of the C-terminal domain. Although this domain contains
neither catalytic residues nor substrate sites, its removal impaired both
catalytic activities, suggesting that it may be essential for active-site
integrity.
PMID- 28420731
TI - Distinct modulatory role of RNA in the aggregation of the tumor suppressor
protein p53 core domain.
AB - Inactivation of the tumor suppressor protein p53 by mutagenesis, chemical
modification, protein-protein interaction, or aggregation has been associated
with different human cancers. Although DNA is the typical substrate of p53,
numerous studies have reported p53 interactions with RNA. Here, we have examined
the effects of RNA of varied sequence, length, and origin on the mechanism of
aggregation of the core domain of p53 (p53C) using light scattering, intrinsic
fluorescence, transmission electron microscopy, thioflavin-T binding, seeding,
and immunoblot assays. Our results are the first to demonstrate that RNA can
modulate the aggregation of p53C and full-length p53. We found bimodal behavior
of RNA in p53C aggregation. A low RNA:protein ratio (~1:50) facilitates the
accumulation of large amorphous aggregates of p53C. By contrast, at a high
RNA:protein ratio (>=1:8), the amorphous aggregation of p53C is clearly
suppressed. Instead, amyloid p53C oligomers are formed that can act as seeds
nucleating de novo aggregation of p53C. We propose that structured RNAs prevent
p53C aggregation through surface interaction and play a significant role in the
regulation of the tumor suppressor protein.
PMID- 28420732
TI - Modulation of TMEM16A channel activity by the von Willebrand factor type A (VWA)
domain of the calcium-activated chloride channel regulator 1 (CLCA1).
AB - Calcium-activated chloride channels (CaCCs) are key players in transepithelial
ion transport and fluid secretion, smooth muscle constriction, neuronal
excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the
activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel
at the cell surface, but the exact mechanism is unknown. Here we demonstrate that
the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal
fragment is necessary and sufficient for this interaction. TMEM16A protein levels
on the cell surface were increased in HEK293T cells transfected with CLCA1
constructs containing the VWA domain, and TMEM16A-like currents were activated.
Similar currents were evoked in cells exposed to secreted VWA domain alone, and
these currents were significantly knocked down by TMEM16A siRNA. VWA-dependent
TMEM16A modulation was not modified by the S357N mutation, a VWA domain
polymorphism associated with more severe meconium ileus in cystic fibrosis
patients. VWA-activated currents were significantly reduced in the absence of
extracellular Mg2+, and mutation of residues within the conserved metal ion
dependent adhesion site motif impaired the ability of VWA to potentiate TMEM16A
activity, suggesting that CLCA1-TMEM16A interactions are Mg2+- and metal ion
dependent adhesion site-dependent. Increase in TMEM16A activity occurred within
minutes of exposure to CLCA1 or after a short treatment with nocodazole,
consistent with the hypothesis that CLCA1 stabilizes TMEM16A at the cell surface
by preventing its internalization. Our study hints at the therapeutic potential
of the selective activation of TMEM16A by the CLCA1 VWA domain in loss-of
function chloride channelopathies such as cystic fibrosis.
PMID- 28420734
TI - MINK1: The missing link between ROS and its inhibition of Th17 cells.
AB - In this issue of JEM, Fu et al. (https://doi.org/10.1084/jem.20161120) identified
the kinase Mink1 as a novel negative regulator of Th17 cell generation. Mink1,
activated by reactive oxygen species (ROS), prevents TGF-beta activation of
Smad2, therefore limiting Th17 cell differentiation.
PMID- 28420733
TI - Detection of interferon alpha protein reveals differential levels and cellular
sources in disease.
AB - Type I interferons (IFNs) are essential mediators of antiviral responses. These
cytokines have been implicated in the pathogenesis of autoimmunity, most notably
systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as
well as monogenic type I interferonopathies. Despite a fundamental role in health
and disease, the direct quantification of type I IFNs has been challenging. Using
single-molecule array (Simoa) digital ELISA technology, we recorded attomolar
concentrations of IFNalpha in healthy donors, viral infection, and complex and
monogenic interferonopathies. IFNalpha protein correlated well with functional
activity and IFN-stimulated gene expression. High circulating IFNalpha levels
were associated with increased clinical severity in SLE patients, and a study of
the cellular source of IFNalpha protein indicated disease-specific mechanisms.
Measurement of IFNalpha attomolar concentrations by digital ELISA will enhance
our understanding of IFN biology and potentially improve the diagnosis and
stratification of pathologies associated with IFN dysregulation.
PMID- 28420735
TI - Correction: The soluble pattern recognition receptor PTX3 links humoral innate
and adaptive immune responses by helping marginal zone B cells.
PMID- 28420736
TI - Deciphering the Regulatory Network between the SREBP Pathway and Protein
Secretion in Neurospora crassa.
AB - Sterol regulatory element binding proteins (SREBPs) are conserved from yeast to
mammalian cells and function in the regulation of sterol homeostasis. In fungi,
the SREBP pathway has been implicated in the adaptation to hypoxia and in
virulence. In Neurospora crassa and Trichoderma reesei, the SREBP pathway also
negatively regulates protein secretion under lignocellulolytic conditions. Here
we utilized global transcriptional profiling combined with genetic and
physiological analyses to address the regulatory link between the SREBP pathway
and protein secretion in N. crassa Our results demonstrated that the function of
the SREBP pathway in ergosterol biosynthesis and adaptation to hypoxia was
conserved in N. crassa Under lignocellulolytic conditions, the SREBP pathway was
highly activated, resulting in the reduced expression of lytic polysaccharide
monooxygenases, which require molecular oxygen for catalytic activity.
Additionally, activation of the SREBP pathway under lignocellulolytic conditions
repressed a set of genes predicted to be involved in the endoplasmic reticulum
stress response. Here we show that the inability of a hac-1 mutant, which bears a
deletion of the major regulator of the unfolded protein response (UPR), to
efficiently produce cellulases and utilize cellulose was suppressed by mutations
in the SREBP pathway. The analyses presented here demonstrated new SREBP pathway
functions, including linkages to the UPR, and provide new clues for genetic
engineering of filamentous fungi to improve their production of extracellular
proteins.IMPORTANCE The role of SREBP transcription factors in the regulation of
sterol biosynthesis is conserved from humans to yeast. In filamentous fungi, this
pathway regulates the secretion of lignocellulolytic enzymes during plant biomass
deconstruction. Here we show that the SREBP pathway in Neurospora crassa
regulates the production of specific cellulases, lytic polysaccharide
monooxygenases that utilize molecular oxygen. Via global transcriptional profile
and genetic analyses, a relationship between the SREBP pathway and the unfolded
protein response (UPR) pathway was revealed, suggesting a regulatory interplay of
these two pathways in the trafficking of plant biomass-degrading enzymes. These
findings have implications for our understanding of the cross talk of the SREBP
and UPR pathways in other organisms and will guide the rational engineering of
fungal strains to improve cellulolytic enzyme production.
PMID- 28420737
TI - Tolerant, Growing Cells from Nutrient Shifts Are Not Persister Cells.
AB - There is much controversy about the metabolic state of cells that are tolerant to
antibiotics, known as persister cells. In this opinion piece, we offer an
explanation for the discrepancy seen: some laboratories are studying
metabolically active and growing cell populations (e.g., as a result of nutrient
shifts) and attributing the phenotypes that they discern to persister cells while
other labs are studying dormant cells. We argue here that the metabolically
active cell population should more accurately be considered tolerant cells, while
the dormant cells are the true persister population.
PMID- 28420738
TI - SAR202 Genomes from the Dark Ocean Predict Pathways for the Oxidation of
Recalcitrant Dissolved Organic Matter.
AB - Deep-ocean regions beyond the reach of sunlight contain an estimated 615 Pg of
dissolved organic matter (DOM), much of which persists for thousands of years. It
is thought that bacteria oxidize DOM until it is too dilute or refractory to
support microbial activity. We analyzed five single-amplified genomes (SAGs) from
the abundant SAR202 clade of dark-ocean bacterioplankton and found they encode
multiple families of paralogous enzymes involved in carbon catabolism, including
several families of oxidative enzymes that we hypothesize participate in the
degradation of cyclic alkanes. The five partial genomes encoded 152 flavin
mononucleotide/F420-dependent monooxygenases (FMNOs), many of which are predicted
to be type II Baeyer-Villiger monooxygenases (BVMOs) that catalyze oxygen
insertion into semilabile alicyclic alkanes. The large number of oxidative
enzymes, as well as other families of enzymes that appear to play complementary
roles in catabolic pathways, suggests that SAR202 might catalyze final steps in
the biological oxidation of relatively recalcitrant organic compounds to
refractory compounds that persist.IMPORTANCE Carbon in the ocean is massively
sequestered in a complex mixture of biologically refractory molecules that
accumulate as the chemical end member of biological oxidation and diagenetic
change. However, few details are known about the biochemical machinery of carbon
sequestration in the deep ocean. Reconstruction of the metabolism of a deep-ocean
microbial clade, SAR202, led to postulation of new biochemical pathways that may
be the penultimate stages of DOM oxidation to refractory forms that persist.
These pathways are tied to a proliferation of oxidative enzymes. This research
illuminates dark-ocean biochemistry that is broadly consequential for
reconstructing the global carbon cycle.
PMID- 28420740
TI - Erratum for Roth et al., "Flavivirus Infection Uncouples Translation Suppression
from Cellular Stress Responses".
PMID- 28420739
TI - The DnaK Chaperone Uses Different Mechanisms To Promote and Inhibit Replication
of Vibrio cholerae Chromosome 2.
AB - Replication of Vibrio cholerae chromosome 2 (Chr2) depends on molecular chaperone
DnaK to facilitate binding of the initiator (RctB) to the replication origin. The
binding occurs at two kinds of site, 12-mers and 39-mers, which promote and
inhibit replication, respectively. Here we show that DnaK employs different
mechanisms to enhance the two kinds of binding. We found that mutations in rctB
that reduce DnaK binding also reduce 12-mer binding and initiation. The
initiation defect is suppressed by second-site mutations that increase 12-mer
binding only marginally. Instead, they reduce replication inhibitory mechanisms:
RctB dimerization and 39-mer binding. One suppressing change was in a
dimerization domain which is folded similarly to the initiator of an iteron
plasmid-the presumed progenitor of Chr2. In plasmids, DnaK promotes initiation by
reducing dimerization. A different mutation was in the 39-mer binding domain of
RctB and inactivated it, indicating an alternative suppression mechanism.
Paradoxically, although DnaK increases 39-mer binding, the increase was also
achieved by inactivating the DnaK binding site of RctB. This result suggests that
the site inhibits the 39-mer binding domain (via autoinhibition) when prevented
from binding DnaK. Taken together, our results reveal an important feature of the
transition from plasmid to chromosome: the Chr2 initiator retains the plasmid
like dimerization domain and its control by chaperones but uses the chaperones in
an unprecedented way to control the inhibitory 39-mer binding.IMPORTANCE The
capacity of proteins to undergo remodeling provides opportunities to control
their function. However, remodeling remains a poorly understood aspect of the
structure-function paradigm due to its dynamic nature. Here we have studied
remodeling of the initiator of replication of Vibrio cholerae Chr2 by the
molecular chaperone, DnaK. We show that DnaK binds to a site on the Chr2
initiator (RctB) that promotes initiation by reducing the initiator's propensity
to dimerize. Dimerization of the initiator of the putative plasmid progenitor of
Chr2 is also reduced by DnaK, which promotes initiation. Paradoxically, the DnaK
binding also promotes replication inhibition by reducing an autoinhibitory
activity of RctB. In the plasmid-to-chromosome transition, it appears that the
initiator has acquired an autoinhibitory activity and along with it a new
chaperone activity that apparently helps to control replication inhibition
independently of replication promotion.
PMID- 28420741
TI - New Mechanism by Which Human Cytomegalovirus MicroRNAs Negate the Proinflammatory
Response to Infection.
AB - Viruses have evolved many novel mechanisms to promote infection and to mitigate
the host cell response to that infection. In the article by M. H. Hancock et al.
(mBio 8:e00109-17, 2017, https://doi.org/10.1128/mBio.00109-17), the authors
describe a new mechanism by which human cytomegalovirus (HCMV) microRNAs (miRNAs;
miR-US5-1 and miR-UL112-3p) negate the proinflammatory response to infection. The
authors document that these two viral miRNAs downregulate the NF-kappaB response
through direct targeting of the IKKalpha and IKKbeta mRNAs, which in turn,
through diminished IkappaB kinases (IKKs), block production of proinflammatory
cytokines (interleukin-6 [IL-6], CCL5, and tumor necrosis factor alpha [TNF
alpha]). Because most signaling pathways that promote NF-kappaB activation and
nuclear translocation ultimately converge on the activation of the IKK complex,
this new study documents that HCMV can strongly dictate how infected cells
respond to internal and/or external stimuli and thus positively influence the
outcome of both lytic and latent infection.
PMID- 28420742
TI - Synergistic Internal Ribosome Entry Site/MicroRNA-Based Approach for Flavivirus
Attenuation and Live Vaccine Development.
AB - The recent emergence of Zika virus underscores the need for new strategies for a
rapid development of safe flavivirus vaccines. Using another flavivirus (Langat
virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we
describe a dual strategy for virus attenuation which synergistically accesses the
specificity of microRNA (miRNA) genome targeting and the effectiveness of
internal ribosome entry site (IRES) insertion. To increase the stability and
immunogenicity of bicistronic LGTVs, we developed a novel approach in which the
capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and
expressed under translational control from an IRES. Engineered bicistronic LGTVs
carrying multiple target sequences for brain-specific miRNAs were stable in Vero
cells and induced adaptive immunity in mice. Importantly, miRNA-targeted
bicistronic LGTVs were not pathogenic for either newborn mice after intracranial
inoculation or adult immunocompromised mice (SCID or type I interferon receptor
knockout) after intraperitoneal injection. Moreover, bicistronic LGTVs were
restricted for replication in tick-derived cells, suggesting an interruption of
viral transmission in nature by arthropod vectors. This approach is suitable for
reliable attenuation of many flaviviruses and may enable development of live
attenuated flavivirus vaccines.IMPORTANCE The recent emergence of Zika virus
underscores the need for new strategies for a rapid development of safe
flavivirus vaccines. Allied separately attenuating approaches based on (i)
microRNA genome targeting and (ii) internal ribosome entry site insertion are not
sufficient for relievable attenuation of neurotropic flavivirus pathogenesis.
Here, we describe a novel dual strategy that combines the specificity of miRNA
based and the effectiveness of IRES-based attenuating approaches, allowing us to
overcome these critical limitations. This developed approach provides a robust
platform for reliable attenuation of many flaviviruses and may enable development
of live flavivirus vaccines.
PMID- 28420743
TI - Cancer cell metabolism: the essential role of the nonessential amino acid,
glutamine.
AB - Biochemistry textbooks and cell culture experiments seem to be telling us two
different things about the significance of external glutamine supply for
mammalian cell growth and proliferation. Despite the fact that glutamine is a
nonessential amino acid that can be synthesized by cells from glucose-derived
carbons and amino acid-derived ammonia, most mammalian cells in tissue culture
cannot proliferate or even survive in an environment that does not contain
millimolar levels of glutamine. Not only are the levels of glutamine in standard
tissue culture media at least ten-fold higher than other amino acids, but
glutamine is also the most abundant amino acid in the human bloodstream, where it
is assiduously maintained at approximately 0.5 mM through a combination of
dietary uptake, de novo synthesis, and muscle protein catabolism. The complex
metabolic logic of the proliferating cancer cells' appetite for glutamine-which
goes far beyond satisfying their protein synthesis requirements-has only recently
come into focus. In this review, we examine the diversity of biosynthetic and
regulatory uses of glutamine and their role in proliferation, stress resistance,
and cellular identity, as well as discuss the mechanisms that cells utilize in
order to adapt to glutamine limitation.
PMID- 28420744
TI - The transcription factor bZIP14 regulates the TCA cycle in the diatom
Phaeodactylum tricornutum.
AB - Diatoms are amongst the most important marine microalgae in terms of biomass, but
little is known concerning the molecular mechanisms that regulate their versatile
metabolism. Here, the pennate diatom Phaeodactylum tricornutum was studied at the
metabolite and transcriptome level during nitrogen starvation and following
imposition of three other stresses that impede growth. The coordinated
upregulation of the tricarboxylic acid (TCA) cycle during the nitrogen stress
response was the most striking observation. Through co-expression analysis and
DNA binding assays, the transcription factor bZIP14 was identified as a regulator
of the TCA cycle, also beyond the nitrogen starvation response, namely in diurnal
regulation. Accordingly, metabolic and transcriptional shifts were observed upon
overexpression of bZIP14 in transformed P. tricornutum cells. Our data indicate
that the TCA cycle is a tightly regulated and important hub for carbon
reallocation in the diatom cell during nutrient starvation and that bZIP14 is a
conserved regulator of this cycle.
PMID- 28420745
TI - Eight principles for patient-centred and family-centred care for newborns in the
neonatal intensive care unit.
AB - Despite the recent improvements in perinatal medical care leading to an increase
in survival rates, adverse neurodevelopmental outcomes occur more frequently in
preterm and/or high-risk infants. Medical risk factors for neurodevelopmental
delays like male gender or intrauterine growth restriction and family
sociocultural characteristics have been identified. Significant data have
provided evidence of the detrimental impact of overhelming environmental sensory
inputs, such as pain and stress, on the developing human brain and strategies
aimed at preventing this impact. These strategies, such as free parental access
or sleep protection, could be considered 'principles of care'. Implementation of
these principles do not require additional research due to the body of evidence.
We review the scientific evidence for these principles here.
PMID- 28420747
TI - CORRECTION.
PMID- 28420749
TI - Inner Workings: 3D printer innovations tackle complexity of metamaterials, living
tissue.
PMID- 28420746
TI - The Mitochondrial DNA-Associated Protein SWIB5 Influences mtDNA Architecture and
Homologous Recombination.
AB - In addition to the nucleus, mitochondria and chloroplasts in plant cells also
contain genomes. Efficient DNA repair pathways are crucial in these organelles to
fix damage resulting from endogenous and exogenous factors. Plant organellar
genomes are complex compared with their animal counterparts, and although several
plant-specific mediators of organelle DNA repair have been reported, many
regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF
(nucleosome remodeling) complex B protein, SWIB5, is capable of associating with
mitochondrial DNA (mtDNA) in Arabidopsis thaliana Gain- and loss-of-function
mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture
and homologous recombination at specific intermediate-sized repeats both under
normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB
proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family
members suggests a link between organellar genome maintenance and cell
proliferation. Taken together, our work presents a protein family that influences
mtDNA architecture and homologous recombination in plants and suggests a link
between organelle functioning and plant development.
PMID- 28420751
TI - Control of potassium homeostasis is an essential function of the second messenger
cyclic di-AMP in Bacillus subtilis.
AB - The second messenger cyclic di-adenosine monophosphate (c-di-AMP) is essential in
the Gram-positive model organism Bacillus subtilis and in related pathogenic
bacteria. It controls the activity of the conserved ydaO riboswitch and of
several proteins involved in potassium (K+) uptake. We found that the YdaO
protein was conserved among several different bacteria and provide evidence that
YdaO functions as a K+ transporter. Thus, we renamed the gene and protein KimA
(K+ importer A). Reporter activity assays indicated that expression beyond the c
di-AMP-responsive riboswitch of the kimA upstream regulatory region occurred only
in bacteria grown in medium containing low K+ concentrations. Furthermore, mass
spectrometry analysis indicated that c-di-AMP accumulated in bacteria grown in
the presence of high K+ concentrations but not in low concentrations. A bacterial
strain lacking all genes encoding c-di-AMP-synthesizing enzymes was viable when
grown in medium containing low K+ concentrations, but not at higher K+
concentrations unless it acquired suppressor mutations in the gene encoding the
cation exporter NhaK. Thus, our results indicated that the control of potassium
homeostasis is an essential function of c-di-AMP.
PMID- 28420752
TI - Highlight: A new way to block the development of asthma from dust mites.
AB - Targeting a transcription factor, generally considered to be "nondruggable," may
help to prevent asthma from developing.
PMID- 28420756
TI - Microbes stimulate hair follicles.
AB - Commensal microbes induce hair follicles to release a chemokine that recruits
regulatory T cells into neonatal skin.
PMID- 28420753
TI - The kinase TPL2 activates ERK and p38 signaling to promote neutrophilic
inflammation.
AB - Tumor progression locus 2 (TPL2; also known as MAP3K8) is a mitogen-activated
protein kinase (MAPK) kinase kinase (MAP3K) that phosphorylates the MAPK kinases
MEK1 and MEK2 (MEK1/2), which, in turn, activate the MAPKs extracellular signal
regulated kinase 1 (ERK1) and ERK2 (ERK1/2) in macrophages stimulated through the
interleukin-1 receptor (IL-1R), Toll-like receptors (TLRs), or the tumor necrosis
factor receptor (TNFR). We describe a conserved and critical role for TPL2 in
mediating the effector functions of neutrophils through the activation of the p38
MAPK signaling pathway. Gene expression profiling and functional studies of
neutrophils and monocytes revealed a MEK1/2-independent branch point downstream
of TPL2 in neutrophils. Biochemical analyses identified the MAPK kinases MEK3 and
MEK6 and the MAPKs p38alpha and p38delta as downstream effectors of TPL2 in these
cells. Genetic ablation of the catalytic activity of TPL2 or therapeutic
intervention with a TPL2-specific inhibitor reduced the production of
inflammatory mediators by neutrophils in response to stimulation with the TLR4
agonist lipopolysaccharide (LPS) in vitro, as well as in rodent models of
inflammatory disease. Together, these data suggest that TPL2 is a drug target
that activates not only MEK1/2-dependent but also MEK3/6-dependent signaling to
promote inflammatory responses.
PMID- 28420757
TI - Stress signals in plants.
AB - Selective autophagy mediates the cross-talk between plant growth and stress
signaling pathways.
PMID- 28420758
TI - The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13
and STAT6 signaling in allergen-exposed mice.
AB - Goblet cell metaplasia and excessive mucus secretion associated with asthma,
cystic fibrosis, and chronic obstructive pulmonary disease contribute to
morbidity and mortality worldwide. We performed a high-throughput screen to
identify small molecules targeting a transcriptional network critical for the
differentiation of goblet cells in response to allergens. We identified RCM-1, a
nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus
production in mice after exposure to allergens. RCM-1 blocked the nuclear
localization and increased the proteasomal degradation of Forkhead box M1
(FOXM1), a transcription factor critical for the differentiation of goblet cells
from airway progenitor cells. RCM-1 reduced airway resistance, increased lung
compliance, and decreased proinflammatory cytokine production in mice exposed to
the house dust mite and interleukin-13 (IL-13), which triggers goblet cell
metaplasia. In cultured airway epithelial cells and in mice, RCM-1 reduced IL-13
and STAT6 (signal transducer and activator of transcription 6) signaling and
prevented the expression of the STAT6 target genes Spdef and Foxa3, which are key
transcriptional regulators of goblet cell differentiation. These results suggest
that RCM-1 is an inhibitor of goblet cell metaplasia and IL-13 signaling,
providing a new therapeutic candidate to treat patients with asthma and other
chronic airway diseases.
PMID- 28420760
TI - Novel lnc RNA regulated by HIF-1 inhibits apoptotic cell death in the renal
tubular epithelial cells under hypoxia.
AB - Chronic tubulointerstitial hypoxia plays an important role as the final common
pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a
master transcriptional factor under hypoxia, regulating downstream target genes.
Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has
clarified various kinds of downstream targets and made it possible to demonstrate
the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1
downstream epigenetic targets which may play important roles in the kidney.
Immortalized tubular cell lines (HK2; human kidney-2) and primary cultured cells
(RPTEC; renal proximal tubular cell lines) were exposed to 1% hypoxia for 24-72
h. We performed RNA-seq to clarify the expression of mRNA and long non-coding RNA
(lncRNA). We also examined ChIP-seq to identify HIF-1 binding sites under
hypoxia. RNA-seq identified 44 lncRNAs which are up-regulated under hypoxic
condition in both cells. ChIP-seq analysis demonstrated that HIF-1 also binds to
the lncRNAs under hypoxia. The expression of novel lncRNA, DARS-AS1 (aspartyl
tRNA synthetase anti-sense 1), is up-regulated only under hypoxia and HIF-1 binds
to its promoter region, which includes two hypoxia-responsive elements. Its
expression is also up-regulated with cobalt chloride exposure, while it is not
under hypoxia when HIF-1 is knocked down by siRNA To clarify the biological roles
of DARS-AS1, we measured the activity of caspase 3/7 using anti-sense oligo of
DARS-AS1. Knockdown of DARS-AS1 deteriorated apoptotic cell death. In conclusion,
we identified the novel lncRNAs regulated by HIF-1 under hypoxia and clarified
that DARS-AS1 plays an important role in inhibiting apoptotic cell death in renal
tubular cells.
PMID- 28420761
TI - In-situ measurements of tensile forces in the tibialis anterior tendon of the rat
in concentric, isometric, and resisted co-contractions.
AB - Tensile-force transmitted by the tibialis anterior (TA) tendon of 11 anesthetized
adult male Wistar rats (body-mass: 360.6 +/- 66.3 g) was measured in-situ within
the intact biomechanical system of the hind-limb using a novel miniature in-line
load-cell. The aim was to demonstrate the dependence of the loading-profile
experienced by the muscle, on stimulation-frequency and the resistance to
shortening in a group of control-animals. Data from these acute-experiments shows
the type of loading achievable by means of implantable electrical stimulators
activating agonists or agonist/antagonist groups of muscles during programmed
resistance-training in freely moving healthy subjects. Force-responses to
electrical stimulation of the common peroneal nerve for single pulses and short
bursts were measured in unloaded and isometric contractions. A less time
consuming approach to measure the force-frequency relationship was investigated
by applying single bursts containing a series of escalating stimulus-frequencies.
We also measured the range of loading attainable by programmed co-contraction of
the TA-muscle with the plantar-flexor muscles for various combinations of
stimulation-frequencies. The maximal average peak-force of single twitches was
179% higher for isometric than for unloaded twitches. Average maximal isometric
tetanic-force per gramme muscle-mass was 16.5 +/- 3.0 N g-1, which agrees well
with other studies. The standard and time-saving approaches to measure the force
frequency relationship gave similar results. Plantar-flexor co-activation
produced greatly increased tension in the TA-tendon, similar to isometric
contractions. Our results suggest that unloaded contractions may not be adequate
for studies of resistance-training. Plantar-flexor co-contractions produced
considerably higher force-levels that may be better suited to investigate the
physiology and cell-biology of resistance-training in rodents.
PMID- 28420762
TI - Resting heart rate variability and exercise capacity in Type 1 diabetes.
AB - People with type 1 diabetes (T1D) have lower exercise capacity (VO2max) than
their age-matched nondiabetic counterparts (CON), which might be related to
cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV;
indicator of cardiac autonomic modulation) was associated with exercise capacity
in those with and without T1D. Twenty-three participants with uncomplicated T1D
and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP;
finger photo-plethysmography), and respiratory rate (respiratory belt) were
measured during baseline, paced-breathing and clinical autonomic reflex tests
(CARTs); deep breathing, lying-to-stand, and Valsalva maneuver. Baseline and
paced-breathing ECG were analyzed for HRV (frequency-domain). Exercise capacity
was determined during an incremental cycle ergometer test while VO2, 12-lead ECG,
and BP were measured. In uncomplicated T1D, resting HR was elevated and resting
HRV metrics were reduced, indicative of altered cardiac parasympathetic
modulation; this was generally undetected by the CARTs. However, BP and plasma
catecholamines were not different between groups. In T1D, VO2max tended to be
lower (P = 0.07) and HR reserve was lower (P < 0.01). Resting Total Power (TP)
had stronger positive associations with VO2max (R2 >= 0.3) than all other
traditional indicators such as age, resting HR, and self-reported exercise (R2 =
0.042-0.3) in both T1D and CON Alterations in cardiac autonomic modulation are an
early manifestation of uncomplicated T1D. Total Power was associated with reduced
exercise capacity regardless of group, and these associations were generally
stronger than traditional indicators.
PMID- 28420764
TI - Erratum.
PMID- 28420763
TI - Reduced body weight gain in ubiquilin-1 transgenic mice is associated with
increased expression of energy-sensing proteins.
AB - Ubiquilin-1 (Ubqln1), a ubiquitin-like protein, is implicated in a variety of
pathophysiological processes, but its role in mediating body weight gain or
metabolism has not been determined. Here, we demonstrate that global
overexpression of Ubqln1 in a transgenic (Tg) mouse reduces the animal's body
weight gain. The decreased body weight gain in Tg mice is associated with lower
visceral fat content and higher metabolic rate. The Ubqln1 Tg mice exhibited
reduced leptin and insulin levels as well as increased insulin sensitivity
manifested by homeostatic model assessment of insulin resistance. Additionally,
the reduced body weight in Tg mice was associated with the upregulation of two
energy-sensing proteins, sirtuin1 (SIRT1) in the hypothalamus and AMP-activated
protein kinase (AMPK) in the skeletal muscle. Consistent with the in vivo
results, overexpression of Ubqln1 significantly increased SIRT1 and AMPK levels
in the mouse embryonic fibroblast cell culture. Thus, our results not only
establish the link between Ubqln1 and body weight regulation but also indicate
that the metabolic function of Ubqln1 on body weight may be through regulating
energy-sensing proteins.
PMID- 28420765
TI - Plan Selection in the Non-Group Market in the First Year of the Health Insurance
Marketplace.
AB - BACKGROUND The Affordable Care Act (ACA)-created Marketplaces reduced barriers to
entry in the non-group health insurance market. Although tax credits were
available to individuals who enrolled in qualified health plans (QHPs) beginning
in 2014, many individuals chose not to switch plans. We examined characteristics
associated with switching from a non-ACA compliant plan to a QHP in 2014 and,
conditional on switching, the characteristics associated with selection of a
specific plan level.METHODS Using claims data from a large commercial insurer, we
examined characteristics associated with switching to a QHP in 2014. For those
who did switch, we used a multinomial logit model to estimate odds of selecting
different metal levels-representing varying degrees of coverage-for a group of
the highest and lowest risk individuals.RESULTS We found individuals most likely
to benefit from the premium and benefit requirements on QHPs were more likely to
switch to QHPs. Individuals at high-risk for high health care expenditures who
had advance premium tax credits (APTCs) had lower odds of choosing a less
generous plan compared to individuals without APTCs (odds of bronze plan over
silver: 0.40, CI: 0.30 - 0.55), while individuals at low-risk of being high cost
with APTCs were more likely to select a plan with a lower premium (odds bronze
plan over silver: 1.35, CI: 1.09 - 1.66).LIMITATIONS This study was conducted
with data from 1 health plan, limiting its national generalizability; however,
this study is a good representation of activity within the state.CONCLUSIONS
APTCs are important for ensuring that less healthy individuals are able to afford
adequate levels of coverage.
PMID- 28420766
TI - Project ACCRUE: Exploring Options to Increase Awareness of AIDS Malignancy
Consortium Clinical Trials in North Carolina.
AB - BACKGROUND Longer lifespans conferred by antiretroviral therapy result in more
time exposed to cancer risk for people living with HIV/AIDS (PLWHA). Given
limited diversity in AIDS Malignancy Consortium (AMC) clinical trials, there is
need for new approaches to educate PLWHA in order to improve awareness and
participation in AMC trials.METHODS With input from a community advisory board,
Project ACCRUE (AMC Clinical Trials at Carolina Ramp Up Enrollment) conducted a
key informant interview with service providers; online organizational surveys of
AMC trial awareness and resource needs; and "lunch and learn" educational
sessions, including pre- and post-intervention knowledge assessments.RESULTS
Providers indicated that transportation, mistrust of the medical community, and
affordability were barriers to trial participation, while printed educational
materials could facilitate trial recruitment. Providers indicated that their
clients had concerns about participating in trials, but also recognized several
benefits of participation including access to medical personnel and treatment,
receipt of monetary incentives, and a feeling of satisfaction from helping
others. In lunch and learn sessions, use of an audience response system to
collect questionnaire data improved scores on knowledge-based items [S(55) = 460;
P < .0001] compared to a pencil and paper test [S(20) = 12.5; P =
.6541].LIMITATIONS Generalizability may have been compromised by the small sample
size. Long-term recall was not measured, and the short retest interval may have
impacted post-intervention assessments.CONCLUSIONS Service providers recognize
the benefits of working with researchers to educate patients about HIV-related
cancers and participation in clinical trials. Lunch and learn sessions improved
knowledge and perceptions about clinical trials for PLWHA.
PMID- 28420767
TI - Vision and Hearing.
PMID- 28420768
TI - Introduction to The NCMJ's Special Issue on Vision and Hearing Loss.
AB - This article introduces NCMJ's special issue on vision and hearing loss. The 13
articles are organized around four areas: 1) screening and early intervention; 2)
technology; 3) prevention; and 4) accommodation, accessibility, and
communication. Together the authors discuss a wide range of potential challenges.
However, importantly, the authors also provide a wealth of resources for
individuals, families, and health care providers.
PMID- 28420769
TI - Newborn Hearing Screening: Making a Difference.
AB - Newborn hearing screening has become the standard of care in the United States,
with over 98% of infants born screened for hearing loss. Appropriate and timely
follow-up is critical when an infant does not pass the screening. While there
remains room for improvement, newborn hearing screening is making a difference.
PMID- 28420770
TI - Accommodating Deaf and Hard-of-Hearing Employees.
AB - Hearing loss is the 2nd most prevalent health issue around the world; in the US,
about 1 in 5 people, and 3 in 5 combat veterans, have some amount of hearing loss
[1]. Managers or supervisors will inevitably have an employee who has some degree
of hearing loss. Employers have a legal obligation to make reasonable
accommodations that enable employees with disabilities, including hearing loss,
to be successful in the workplace.
PMID- 28420771
TI - Updates in Hearing Technology.
AB - Advances in hearing technology offer patients with hearing loss even better ways
to improve communication and quality of life. Hearing devices are more convenient
and compatible than ever, with wireless connectivity to smartphones and lithium
ion rechargeable batteries, while improved surgical techniques widen the
candidacy for cochlear implants to those with more residual hearing.
PMID- 28420772
TI - Health Care for Individuals with Hearing Loss or Vision Loss: A Minefield of
Barriers to Accessibility.
AB - Individuals with hearing or vision loss face significant barriers in accessing
health care, resulting in documented health inequities. These barriers are
typically in the form of inaccessible communication or information, as well as
impediments to orientation or mobility. Compliance with applicable accessibility
laws, such as the Americans with Disabilities Act, requires that providers have a
sound understanding of the specific aids and services that assure compliance.
PMID- 28420773
TI - Are Direct-to-Consumer Marketing and Over-the-Counter Sale of Hearing Aids
Beneficial to Patients with Hearing Loss? A Provider's Perspective.
PMID- 28420774
TI - Preventing Noise-Induced Hearing Loss.
AB - Noise-induced hearing loss (NIHL) is second only to presbycusis, age-related
hearing loss, as a cause of hearing impairment; yet, it is preventable. This
commentary summarizes the effects of noise on hearing, relevant workplace
regulations, and ways to minimize excessive noise's deleterious impact on
individuals' quality of life on and off the job.
PMID- 28420775
TI - The Prevalence and Impact of Vision and Hearing Loss in the Elderly.
AB - With a rapidly aging population, awareness of sensory impairments in the older
adult population is crucial. Vision and hearing loss, in particular, have a
prominent impact on quality of life. Understanding the prevalence and impact of
these impairments is important to help patients preserve and maintain a good
quality of life.
PMID- 28420776
TI - Screening for Diabetic Retinopathy: Strategies for Improving Patient Follow-up.
AB - Diabetic retinopathy is a leading cause of preventable blindness. Timely
screening and treatment prevent morbidity, though low follow-up rates remain
problematic. Feasible and efficacious methods for increasing screening follow-up
rates include patient education, a streamlined referral and scheduling process,
and collaboration with local ophthalmologists and primary care providers.
PMID- 28420777
TI - Retinopathy of Prematurity.
AB - Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder unique
to premature infants. As premature births increase in many areas of the world,
ROP has become a leading cause of childhood blindness. A better understanding of
the pathogenesis of ROP, adherence to strict screening guidelines, and evolution
of treatment options have reduced the number of sight-threatening complications
from ROP.
PMID- 28420778
TI - Empowering Adolescents Who Are Deaf and Hard of Hearing.
AB - The adolescent years are challenging for all kids. If hearing loss is added into
the mix, the issues faced by these teens are quite complex and require some skill
development in advocacy, empowerment, and independence. This article will explore
the emotional journey of the individual and the family.
PMID- 28420779
TI - Patient-Provider Communication in the Context of Hearing Loss.
AB - Hearing is the primary mechanism through which most of us receive ideas from
other people. When that ability is altered, it affects how we interpret and react
to information. In a physician's office, the transfer of thought is critical to
ensuring that patients understand their healthcare information and are compliant
with things like medication. In this article, we discuss ways to enhance that
communication.
PMID- 28420780
TI - Running the Numbers: Understanding the Prevalence of Eye and Ear Injuries in
North Carolina.
PMID- 28420781
TI - Philanthropy Profile: Promoting the Importance of Screenings for Healthier Sight
and Sound.
PMID- 28420782
TI - Downward Trends in Medicaid Costs: Let's Recognize What's Been Working!
PMID- 28420783
TI - Block Grants Would Strip Medicaid Coverage for Low Income North Carolinians.
PMID- 28420784
TI - Death Rates from Unintentional and Undetermined Prescription Opioid Overdoses and
Dispensing Rates of Controlled Prescription Opioid Analgesics - 2011-2015.
PMID- 28420785
TI - Bringing disorder and dynamics in protein allostery into focus.
PMID- 28420786
TI - Memory-n strategies of direct reciprocity.
AB - Humans routinely use conditionally cooperative strategies when interacting in
repeated social dilemmas. They are more likely to cooperate if others cooperated
before, and are ready to retaliate if others defected. To capture the emergence
of reciprocity, most previous models consider subjects who can only choose from a
restricted set of representative strategies, or who react to the outcome of the
very last round only. As players memorize more rounds, the dimension of the
strategy space increases exponentially. This increasing computational complexity
renders simulations for individuals with higher cognitive abilities infeasible,
especially if multiplayer interactions are taken into account. Here, we take an
axiomatic approach instead. We propose several properties that a robust
cooperative strategy for a repeated multiplayer dilemma should have. These
properties naturally lead to a unique class of cooperative strategies, which
contains the classical Win-Stay Lose-Shift rule as a special case. A
comprehensive numerical analysis for the prisoner's dilemma and for the public
goods game suggests that strategies of this class readily evolve across various
memory-n spaces. Our results reveal that successful strategies depend not only on
how cooperative others were in the past but also on the respective context of
cooperation.
PMID- 28420787
TI - Activation of NLRP3 inflammasome complex potentiates venous thrombosis in
response to hypoxia.
AB - Venous thromboembolism (VTE), caused by altered hemostasis, remains the third
most common cause of mortality among all cardiovascular conditions. In addition
to established genetic and acquired risk factors, low-oxygen environments also
predispose otherwise healthy individuals to VTE. Although disease etiology
appears to entail perturbation of hemostasis pathways, the key molecular
determinants during immediate early response remain elusive. Using an established
model of venous thrombosis, we here show that systemic hypoxia accelerates
thromboembolic events, functionally stimulated by the activation of nucleotide
binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3)
inflammasome complex and increased IL-1beta secretion. Interestingly, we also
show that the expression of NLRP3 is mediated by hypoxia-inducible factor 1-alpha
(HIF-1alpha) during these conditions. The pharmacological inhibition of caspase
1, in vivo knockdown of NLRP3, or HIF-1alpha other than IL-1beta-neutralizing
antibodies attenuated inflammasome activation and curtailed thrombosis under
hypoxic conditions. We extend the significance of these preclinical findings by
studying modulation of this pathway in patients with altitude-induced venous
thrombosis. Our results demonstrate distinctive, increased expression of NLRP3,
caspase-1, and IL-1beta in individuals with clinically established venous
thrombosis. We therefore propose that an early proinflammatory state in the
venous milieu, orchestrated by the HIF-induced NLRP3 inflammasome complex, is a
key determinant of acute thrombotic events during hypoxic conditions.
PMID- 28420788
TI - Reconstructing the spectrotemporal modulations of real-life sounds from fMRI
response patterns.
AB - Ethological views of brain functioning suggest that sound representations and
computations in the auditory neural system are optimized finely to process and
discriminate behaviorally relevant acoustic features and sounds (e.g.,
spectrotemporal modulations in the songs of zebra finches). Here, we show that
modeling of neural sound representations in terms of frequency-specific
spectrotemporal modulations enables accurate and specific reconstruction of real
life sounds from high-resolution functional magnetic resonance imaging (fMRI)
response patterns in the human auditory cortex. Region-based analyses indicated
that response patterns in separate portions of the auditory cortex are
informative of distinctive sets of spectrotemporal modulations. Most relevantly,
results revealed that in early auditory regions, and progressively more in
surrounding regions, temporal modulations in a range relevant for speech analysis
(~2-4 Hz) were reconstructed more faithfully than other temporal modulations. In
early auditory regions, this effect was frequency-dependent and only present for
lower frequencies (<~2 kHz), whereas for higher frequencies, reconstruction
accuracy was higher for faster temporal modulations. Further analyses suggested
that auditory cortical processing optimized for the fine-grained discrimination
of speech and vocal sounds underlies this enhanced reconstruction accuracy. In
sum, the present study introduces an approach to embed models of neural sound
representations in the analysis of fMRI response patterns. Furthermore, it
reveals that, in the human brain, even general purpose and fundamental neural
processing mechanisms are shaped by the physical features of real-world stimuli
that are most relevant for behavior (i.e., speech, voice).
PMID- 28420789
TI - Structural and stereoelectronic insights into oxygenase-catalyzed formation of
ethylene from 2-oxoglutarate.
AB - Ethylene is important in industry and biological signaling. In plants, ethylene
is produced by oxidation of 1-aminocyclopropane-1-carboxylic acid, as catalyzed
by 1-aminocyclopropane-1-carboxylic acid oxidase. Bacteria catalyze ethylene
production, but via the four-electron oxidation of 2-oxoglutarate to give
ethylene in an arginine-dependent reaction. Crystallographic and biochemical
studies on the Pseudomonas syringae ethylene-forming enzyme reveal a branched
mechanism. In one branch, an apparently typical 2-oxoglutarate oxygenase reaction
to give succinate, carbon dioxide, and sometimes pyrroline-5-carboxylate occurs.
Alternatively, Grob-type oxidative fragmentation of a 2-oxoglutarate-derived
intermediate occurs to give ethylene and carbon dioxide. Crystallographic and
quantum chemical studies reveal that fragmentation to give ethylene is promoted
by binding of l-arginine in a nonoxidized conformation and of 2-oxoglutarate in
an unprecedented high-energy conformation that favors ethylene, relative to
succinate formation.
PMID- 28420790
TI - Honeybee gut microbiota promotes host weight gain via bacterial metabolism and
hormonal signaling.
AB - Social bees harbor a simple and specialized microbiota that is spatially
organized into different gut compartments. Recent results on the potential
involvement of bee gut communities in pathogen protection and nutritional
function have drawn attention to the impact of the microbiota on bee health.
However, the contributions of gut microbiota to host physiology have yet to be
investigated. Here we show that the gut microbiota promotes weight gain of both
whole body and the gut in individual honey bees. This effect is likely mediated
by changes in host vitellogenin, insulin signaling, and gustatory response. We
found that microbial metabolism markedly reduces gut pH and redox potential
through the production of short-chain fatty acids and that the bacteria adjacent
to the gut wall form an oxygen gradient within the intestine. The short-chain
fatty acid profile contributed by dominant gut species was confirmed in vitro.
Furthermore, metabolomic analyses revealed that the gut community has striking
impacts on the metabolic profiles of the gut compartments and the hemolymph,
suggesting that gut bacteria degrade plant polymers from pollen and that the
resulting metabolites contribute to host nutrition. Our results demonstrate how
microbial metabolism affects bee growth, hormonal signaling, behavior, and gut
physicochemical conditions. These findings indicate that the bee gut microbiota
has basic roles similar to those found in some other animals and thus provides a
model in studies of host-microbe interactions.
PMID- 28420792
TI - Morality constrains the default representation of what is possible.
AB - The capacity for representing and reasoning over sets of possibilities, or modal
cognition, supports diverse kinds of high-level judgments: causal reasoning,
moral judgment, language comprehension, and more. Prior research on modal
cognition asks how humans explicitly and deliberatively reason about what is
possible but has not investigated whether or how people have a default, implicit
representation of which events are possible. We present three studies that
characterize the role of implicit representations of possibility in cognition.
Collectively, these studies differentiate explicit reasoning about possibilities
from default implicit representations, demonstrate that human adults often
default to treating immoral and irrational events as impossible, and provide a
case study of high-level cognitive judgments relying on default implicit
representations of possibility rather than explicit deliberation.
PMID- 28420791
TI - Adult enteric nervous system in health is maintained by a dynamic balance between
neuronal apoptosis and neurogenesis.
AB - According to current dogma, there is little or no ongoing neurogenesis in the
fully developed adult enteric nervous system. This lack of neurogenesis leaves
unanswered the question of how enteric neuronal populations are maintained in
adult guts, given previous reports of ongoing neuronal death. Here, we confirm
that despite ongoing neuronal cell loss because of apoptosis in the myenteric
ganglia of the adult small intestine, total myenteric neuronal numbers remain
constant. This observed neuronal homeostasis is maintained by new neurons formed
in vivo from dividing precursor cells that are located within myenteric ganglia
and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation
of the phosphatase and tensin homolog gene in this pool of adult precursors leads
to an increase in enteric neuronal number, resulting in ganglioneuromatosis,
modeling the corresponding disorder in humans. Taken together, our results show
significant turnover and neurogenesis of adult enteric neurons and provide a
paradigm for understanding the enteric nervous system in health and disease.
PMID- 28420793
TI - Regulating plant physiology with organic electronics.
AB - The organic electronic ion pump (OEIP) provides flow-free and accurate delivery
of small signaling compounds at high spatiotemporal resolution. To date, the
application of OEIPs has been limited to delivery of nonaromatic molecules to
mammalian systems, particularly for neuroscience applications. However, many long
standing questions in plant biology remain unanswered due to a lack of technology
that precisely delivers plant hormones, based on cyclic alkanes or aromatic
structures, to regulate plant physiology. Here, we report the employment of OEIPs
for the delivery of the plant hormone auxin to induce differential concentration
gradients and modulate plant physiology. We fabricated OEIP devices based on a
synthesized dendritic polyelectrolyte that enables electrophoretic transport of
aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana
seedlings in vivo was monitored in real time via dynamic fluorescent auxin
response reporters and induced physiological responses in roots. Our results
provide a starting point for technologies enabling direct, rapid, and dynamic
electronic interaction with the biochemical regulation systems of plants.
PMID- 28420794
TI - Structural features and lipid binding domain of tubulin on biomimetic
mitochondrial membranes.
AB - Dimeric tubulin, an abundant water-soluble cytosolic protein known primarily for
its role in the cytoskeleton, is routinely found to be associated with
mitochondrial outer membranes, although the structure and physiological role of
mitochondria-bound tubulin are still unknown. There is also no consensus on
whether tubulin is a peripheral membrane protein or is integrated into the outer
mitochondrial membrane. Here the results of five independent techniques-surface
plasmon resonance, electrochemical impedance spectroscopy, bilayer overtone
analysis, neutron reflectometry, and molecular dynamics simulations-suggest that
alpha-tubulin's amphipathic helix H10 is responsible for peripheral binding of
dimeric tubulin to biomimetic "mitochondrial" membranes in a manner that
differentiates between the two primary lipid headgroups found in mitochondrial
membranes, phosphatidylethanolamine and phosphatidylcholine. The identification
of the tubulin dimer orientation and membrane-binding domain represents an
essential step toward our understanding of the complex mechanisms by which
tubulin interacts with integral proteins of the mitochondrial outer membrane and
is important for the structure-inspired design of tubulin-targeting agents.
PMID- 28420795
TI - Reply to Brown and Behrmann, Cox, et al., and Kessler et al.: Data and code
sharing is the way forward for fMRI.
PMID- 28420796
TI - Reevaluating "cluster failure" in fMRI using nonparametric control of the false
discovery rate.
PMID- 28420797
TI - Controversy in statistical analysis of functional magnetic resonance imaging
data.
PMID- 28420798
TI - fMRI clustering and false-positive rates.
PMID- 28420799
TI - Neonatal hypothyroidism does not increase Sertoli cell proliferation in iNOS-/-
mice.
AB - Sertoli cell (SC) proliferation in mice occurs until two weeks after birth and is
mainly regulated by FSH and thyroid hormones. Previous studies have shown that
transient neonatal hypothyroidism in laboratory rodents is able to extend SC
mitotic activity, leading ultimately to higher testis size and daily sperm
production (DSP) in adult animals. Moreover, we have shown that due to higher SC
proliferation and lower germ cell apoptosis, iNOS deficiency in mice also results
in higher testis size and DSP. Although the cell size was smaller, the Leydig
cells (LCs) number per testis also significantly increased in iNOS-/- mice. Our
aims in the present study were to investigate if the combination of neonatal
hypothyroidism and iNOS deficiency promotes additive effects in SC number, testis
size and DSP. Hypothyroidism was induced in wild-type (WT) and iNOS-/- mice using
6-propyl-2-thiouracil (PTU) through the mother's drinking water from 0 to 20 days
of age, and were sacrificed at adulthood. Our results showed that, in contrast to
the WT mice in which testis size, DSP and SC numbers increased significantly by
20, 40 and 70% respectively, after PTU treatment, no additive effects were
observed for these parameters in treated iNOS-/- mice, as well as for LC. No
alterations were observed in spermatogenesis in any group evaluated. Although we
still do not have an explanation for these intriguing findings, we are currently
investigating whether thyroid hormones influence iNOS levels and/or
counterbalance physiological effects of iNOS deficiency in testis function and
spermatogenesis.
PMID- 28420800
TI - SETDB1 plays an essential role in maintenance of gonocyte survival in pigs.
AB - Histone methyltransferase SETDB1 suppresses gene expression and modulates
heterochromatin formation through H3K9me2/3. Previous studies have revealed that
SETDB1 catalyzes lysine 9 of histone H3 tri-methylation and plays essential roles
in maintaining the survival of embryonic stem cells and spermatogonial stem cells
in mice. However, the function of SETDB1 in porcine male germ cells remains
unclear. The aim of the present study was to reveal the expression profile and
function of SETDB1 in porcine germ cells. SETDB1 expression gradually increased
during testis development. SETDB1 was strongly localized in gonocytes. Knockdown
of SETDB1 gene expression led to gonocyte apoptosis and a decrease in H3K27me3,
but no significant change in H3K9me3. These observations suggested that SETDB1 is
a novel epigenetic regulator of porcine male germ cells, and contributes to the
maintenance of gonocyte survival in pigs, probably due to the regulation of
H3K27me3 rather than H3K9me3. These findings will provide a theoretical basis for
the future study of epigenetic regulation of spermatogenesis.
PMID- 28420801
TI - The impact of laparoscopic ovarian drilling on AMH and ovarian reserve: a meta
analysis.
AB - Laparoscopic ovarian drilling (LOD) has been widely used as an effective
treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However,
there has been a growing concern over a possible damaging effect of this
procedure on ovarian reserve. The objective of this study was to investigate the
hypothesis that LOD compromises ovarian reserve as measured by post-operative
changes in circulating anti-Mullerian hormone (AMH). This meta-analysis included
all cohort studies as well as randomised controlled trials (RCTs) investigating
serum AMH concentrations and other ovarian reserve markers in women with PCOS
undergoing LOD. Various databases were searched including MEDLINE, EMBASE,
Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane
Library from January 2000 to December 2016. Sixty studies were identified, of
which seven were deemed eligible for this review. AMH data were extracted from
each study and entered into the RevMan software to calculate the weighted mean
difference (WMD) between pre- and post-operative values. Pooled analysis of all
studies (n = 442) revealed a statistically significant decline in serum AMH
concentration after LOD (WMD -2.13 ng/mL; 95% confidence interval (CI) -2.97 to
1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of
surgery and amount of energy applied during LOD consistently showed a
statistically significant fall in serum AMH concentration. In conclusion,
although LOD seems to markedly reduce circulating AMH, it remains uncertain
whether this reflects a real damage to ovarian reserve or normalisation of the
high pre-operative serum AMH levels. Further long-term studies on ovarian reserve
after LOD are required to address this uncertainty.
PMID- 28420802
TI - Clinical Decision-Making for the Hemodynamic "Gray Zone" (FFR 0.75-0.80) and Long
Term Outcomes.
AB - BACKGROUND: Fractional flow reserve (FFR) value between 0.75 and 0.80 is
considered the "gray zone" and outcomes data relative to treatment strategy
(revascularization vs medical therapy alone [deferral]) are limited for this
group. METHODS AND RESULTS: A total of 238 patients (64.3 +/- 8.6 years; 97%
male; 45% diabetic) with gray-zone FFR were followed for the primary endpoint of
major adverse cardiovascular event (MACE), defined as a composite of death,
myocardial infarction (MI), and target-vessel revascularization. Mean follow-up
duration was 30 +/- 17 months. Deferred patients (n = 48 [20%]) had a higher
prevalence of smoking and chronic kidney disease compared with the percutaneous
coronary intervention (PCI) group (n = 190 [80%]; P<.05). Patients who underwent
PCI had significantly lower MACE compared with the deferred patients (16% vs 40%;
log rank P<.01). While there was a trend toward a decrease in all-cause mortality
(8% vs 19%; log rank P=.06), the composite of death or MI was significantly lower
in the PCI group (9% vs 27%; P<.01). On multivariate Cox proportional hazards
regression analysis, PCI was associated with lower MACE (hazard ratio, 0.5; 95%
confidence interval, 0.27-0.95; P=.03). CONCLUSION: Revascularization for
patients with gray-zone FFR was associated with a significantly reduced risk of
MACE compared with medical therapy alone.
PMID- 28420803
TI - Comparison of the American College of Cardiology/American Heart Association and
the European Society of Cardiology Guidelines for the Management of Patients With
Valvular Heart Disease.
AB - BACKGROUND: The American College of Cardiology/American Heart Association
(ACC/AHA) and the European Society of Cardiology (ESC) have developed guidelines
to assist clinicians in making evidence-based decisions. This study compares the
ACC/AHA and ESC guidelines for the management of patients with valvular heart
disease (VHD). METHODS: The current ACC/AHA and ESC guidelines for VHD, last
updated in 2014 and 2012, respectively, were compared by class of recommendation
(COR), level of evidence (LOE), and content. RESULTS: The ACC/AHA and ESC VHD
guidelines contain 229 and 85 recommendations, respectively. The COR
distributions of the ACC/AHA and ESC VHD guidelines were 47.6% vs 44.7% class I
[P=.65]; 46.3% vs 55.3% class II [P=.16]; and 6.1% vs 0.0% class III [P=.01],
respectively. The LOE distributions were 3.1% vs 0.0% LOE A [P=.20]; 47.2% vs
10.6% LOE B [P<.001]; and 49.8% vs 89.4% LOE C [P<.001], respectively. The
recommendation type distributions were 31.0% vs 2.4% diagnostic [P<.001]; 23.1%
vs 16.5% medical therapy [P=.20]; and 45.9% vs 81.2% interventional/surgical
recommendations [P<.001], respectively. The content of the guidelines was
similar, with only minor differences in a few recommendations. CONCLUSIONS: The
ACC/AHA VHD guidelines contain significantly more recommendations. The
distribution of COR was similar, but the ACC/AHA guidelines included more LOE B
recommendations and fewer LOE C recommendations, suggesting that the ACC/AHA
guidelines place greater emphasis on published data than expert opinion. Overall,
the ACC/AHA and ESC guidelines provide similar recommendations, suggesting
consistency in practice; however, the relative paucity of LOE A recommendations
highlights the need for additional research.
PMID- 28420804
TI - Contemporary Trends and Outcomes Associated With the Preprocedural Use of Oral
P2Y12 Inhibitors in Patients Undergoing Percutaneous Coronary Intervention:
Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
(BMC2).
AB - OBJECTIVES: We sought to describe trends in the use of preprocedural P2Y12
inhibitors and their clinical impact in patients undergoing percutaneous coronary
intervention (PCI). BACKGROUND: Oral P2Y12 inhibitors are ubiquitously used
medications; however, the specific timing of initial P2Y12 inhibitor
administration remains intensely debated. METHODS: Our study population comprised
74,053 consecutive patients undergoing PCI at 47 hospitals in Michigan from
January 2013 through June 2015. In-hospital outcomes included stent thrombosis,
bleeding, need for transfusion, and death. Hierarchical logistic regression,
propensity matching, and targeted maximum likelihood estimation were used to
adjust for baseline patient differences and clustering, and to minimize bias.
RESULTS: Of 24,733 patients who received a preprocedural P2Y12 inhibitor, 82%
received clopidogrel, 8% prasugrel, and 10% ticagrelor. Preprocedural
administration of P2Y12 inhibitors declined during the study (49.3% to 24.8%;
P<.001), and varied greatly across hospitals (14.5%-95.9%). No significant
differences in outcomes were observed between patients receiving preprocedural
clopidogrel and a matched cohort of those not receiving any preprocedural P2Y12
inhibitor (stent thrombosis: adjusted odds ratio [OR], 1.55; 95% confidence
interval [CI], 0.30-7.84; bleeding: OR, 0.96; 95% CI, 0.63-1.46; transfusion: OR,
1.03; 95% CI, 0.69-1.55; and death: OR, 0.95; 95% CI, 0.38-2.37). Similar
findings were demonstrated for preprocedural ticagrelor and prasugrel. Results
from a subgroup analysis of patients with non-ST segment elevation acute coronary
syndrome (n = 28,072) were consistent with the overall findings. CONCLUSIONS:
There was a substantial decline in the rate of preprocedural P2Y12 inhibitor
administration during the study. Furthermore, there were no significant
differences in outcomes between patients treated with preprocedural P2Y12
inhibitors and those who were not.
PMID- 28420805
TI - Immunotherapeutic approaches for hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the
fact that the diagnosis usually occurs at anadvanced stage. Even in case of
curative surgical treatment, recurrence is common. Sorafenib and regorafenib are
the only therapeutic agents that have been demonstrated to be effective in
advanced HCC, thus novel curative approaches are urgently needed. Recent studies
focus on the role of immune system in HCC. In fact, the unique immune response in
the liver favors tolerance, which can represent a real challenge for conventional
immunotherapy in these patients. Spontaneous immune responses against tumor
antigens have been detected, and new immune therapies are under investigation:
dendritic cell vaccination, immune-modulator strategy, and immune checkpoint
inhibition. In recent years different clinical trials examining the use of
immunotherapy to treat HCC have been conducted with initial promising results.
This review article will summarize the literature data concerning the potential
immunotherapeutic approaches in HCC patients.
PMID- 28420806
TI - The association of occupational metals exposure and oxidative damage, telomere
shortening in fitness equipments manufacturing workers.
AB - The welding is the major working process in fitness equipment manufacturing
industry, and International Agency for Research on Cancer has classified welding
fumes as possibly carcinogenic to humans (Group 2B). The present study aimed to
evaluate associations between the occupational exposure of metals and oxidative
damage and telomere length shortening in workers involved in the manufacture of
fitness equipment. The blood metal concentrations were monitored and
malondialdehyde (MDA), alkaline Comet assay was determined as oxidative damage in
117 workers from two representative fitness equipment manufacturing plants. MDA
levels varied according to workers' roles at the manufacturing plants, and showed
a trend as cutting>painting>welding>administration workers. Welders had
marginally shorter average telomere lengths than the administrative workers
(p=0.058). Cr and Mn levels were significantly greater in welders than they were
in administrative workers. There were significantly positive correlations between
MDA and Cr and Mn levels, the major components of welding fume. However, the
association would be eliminated if co-metals exposure were considered
simultaneously. In future, telomere length and MDA might be potential biomarkers
for predicting cardiovascular disease in co-metals exposed workers.
PMID- 28420807
TI - Effects of modifications to the health and social sector's collective agreement
on the objective characteristics of working hours.
AB - This study aimed to evaluate the effects of an intervention on objective working
hour characteristics. The intervention involved making modifications to the
collective agreement that would limit employees' entitlement to time off as
compensation. The intervention group consisted of 493 and the control group of
2,303 health and social care shift workers, respectively. We analysed the
objective pay roll-based working-hour data for 2012-2013, which we obtained from
employers' records, using the repeated measures mixed model. The changes in
objective working-hour characteristics were small, but systematic. The
intervention had some positive effects: the amount of short recovery periods (<28
h) after the last night shift decreased from 5% to 3%, and the amount of working
weeks of over 48 h decreased from 19% to 17%. The realization of employees' shift
preferences increased from 18% to 20%. However, in contrast, consecutive work
shifts and the number of scheduled absences increased and days off decreased,
suggesting less time for recovery and thus a negative trend in shift ergonomics.
When planning shifts, nursing management should avoid regulations that promote
specific unhealthy shift characteristics, that is, consecutive work shifts and
less days off.
PMID- 28420810
TI - Brain Tumor Registry of Japan (2005-2008).
PMID- 28420811
TI - The T Allele of rs8075977 in the 5'-Flanking Region of the PEDF Gene Is
Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men.
AB - Coronary artery disease (CAD) is a multifactorial disease with a genetic
component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory,
anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received
increasing attention as a sensitive biomarker of atherosclerosis and CAD. To
explore the potential association between PEDF single nucleotide polymorphisms
(SNPs) and CAD, we performed this case-control study of consecutive elderly
Chinese Han male patients (n = 416) and age-matched male controls (n = 528)
without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD
patients (age >= 60 years) are not biologically related. A tag approach was used
to examine 100% of common variations in the PEDF gene (r2 >= 0.8, minor allele
frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB
which describes the common patterns of human DNA sequence variation and Tagger
program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs
(rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634)
were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'
flanking region, showed the significant effect on the susceptibility to CAD. The
frequency of its T allele was significantly higher in the controls (52.7%) than
that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005).
In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF
gene may be protective for CAD. Conversely, the C allele at this variation site
is associated with CAD in elderly Chinese Han men.
PMID- 28420808
TI - Sequence variations in estrogen receptor 1 and 2 genes and their association with
egg production traits in Chinese Dagu chickens.
AB - Estrogen receptors alpha (ESR1) and beta (ESR2) play central roles in
folliculogenesis and therefore in reproductive biology. In the present study, two
single nucleotide polymorphisms (SNPs) were identified in the ESR1 and ESR2 genes
using PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing.
One of the identified SNPs, a T1101C transition located within exon 4 of the ESR1
gene, was significantly associated with hen-housed egg production (HHEP) at 30,
43, 57 and 66 weeks of age (P<0.05), and egg weight (EW) at 30 weeks (P<0.05).
Another SNP, a G1755A transition leading to a non-synonymous substitution (valine
459-to-isoleucine) located within exon 8 of the ESR2 gene, was also markedly
correlated with the HHEP at 30, 43, 57 and 66 weeks of age (P<0.05), and EW at 30
weeks (P<0.05). A greater proportion of the additive variance was explained by
the SNPs for most of the associated egg production traits (>1%). Furthermore, the
results of the combined genotype-based association analysis supported the finding
that the two SNPs were associated with the traits under a study. Taken together,
our findings suggest that the two sequence variations in the ESR1 and ESR2 genes
may provide promising genetic markers for the early selection and prediction of
advantageous phenotypes in chicken breeding.
PMID- 28420812
TI - Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord
blood cells.
AB - Umbilical cord blood (UCB) has advantages over other tissues because it can be
obtained without an invasive procedure and complex processing. We explored the
availability of cryopreserved UCB cells as a source of mesenchymal stromal/stem
cells (MSCs). MSCs were successfully isolated from six of 30 UCB units (median
volume, 34.0 mL; median nucleated cell number, 4.4*108) that were processed and
cryopreserved using CP-1/human serum albumin. This isolation rate was lower than
that (57%) from non-cryopreserved UCB cells. The number of nucleated cells before
and after hydroxyethyl starch separation, UCB unit volume, and cell viability
after thawing did not significantly differ between UCB units from which MSCs were
successfully isolated and those from which they were not. When CryoSure-DEX40 was
used as a cryoprotectant, MSCs were isolated from two of ten UCB units. Logistic
regression analysis demonstrated that the cryopreservation method was not
significantly associated with the success of MSC isolation. The isolated MSCs had
a similar morphology and surface marker expression profile as bone marrow-derived
MSCs and were able to differentiate into osteogenic, adipogenic, and chondrogenic
cells. In summary, MSCs can be isolated from cryopreserved UCB cells. However,
the cryopreservation process reduces the isolation rate; therefore, freshly
donated UCB cells are preferable for the isolation of MSCs.
PMID- 28420813
TI - Establishment of cell lines from adult T-cell leukemia cells dependent on
negatively charged polymers.
AB - Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here,
we examined the effects of static electricity in the culture medium on the
proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in
vitro and thus had to be cultured in a medium containing negatively charged
polymers. In the presence of poly-gamma-glutamic acid (PGA) or chondroitin
sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same
single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing
OX40L (OX40L+HK). Dextran sulfate inhibited growth in both HKOX3 cell lines. Both
PGA and OX40L+HK were indispensable for HKOX3-PGA growth, but HKOX3-CDR could
proliferate in the presence of CDR or OX40L+HK alone. Thus, the specific action
of each negatively charged polymer promoted the growth of specific ATLL cells in
vitro.
PMID- 28420814
TI - Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma
cells is not involved in the interaction with macrophages.
AB - Cell adhesion molecule 1 (CADM1) is a cell adhesion molecule that is expressed in
brain, liver, lung, testis, and some kinds of cancer cells including adult T-cell
leukemia/lymphoma (ATLL). Recent studies have indicated the involvement of CADM1
in cell-cell contact between cytotoxic T-lymphocytes and virus infected cells. We
previously reported that cell-cell interaction between lymphoma cells and
macrophages induces lymphoma cell proliferation. In the present study, we
investigated whether CADM1 is associated with cell-cell interaction between
several human lymphoma cell lines and macrophages.CADM1 expression was observed
in the ATLL cell lines, ATN-1, ATL-T, and ATL-35T, and in the B cell lymphoma
cell lines, TL-1, DAUDI, and SLVL, using western blotting. Significant cell-cell
interaction between macrophages and ATN-1, ATL-T, ATL-35T and MT-2, DAUDI, and
SLVL cells, as assessed by induction of cell proliferation, was observed.
Immunohistochemical analysis of human biopsy samples indicated CADM1 expression
in 10 of 14 ATLL cases; however, no case of follicular lymphoma or diffuse large
B-cell lymphoma was positive for CADM1. Finally, the interaction of macrophages
with cells of the CADM1-negative ED ATLL cell line and CADM1-transfected ED cells
was tested. However, significant cell-cell interaction between macrophage and
CADM1-transfected ED cells was not observed. We conclude that CADM1 was not
associated with cell-cell interaction between lymphoma cells and macrophages,
although CADM1 may be a useful marker of ATLL for diagnostic procedures.
PMID- 28420815
TI - Early Repolarization Pattern Predicts the Increased Risk of Ventricular
Arrhythmias in Patients With Acute Anterior ST-Segment Elevation Myocardial
Infarction - A Propensity Analysis.
AB - BACKGROUND: The association between the early repolarization pattern (ERP) and
ventricular arrhythmias in patients with ST-segment elevation myocardial
infarction (STEMI) remains uncertain. We hypothesized that ERP predicts the risk
of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) during
the acute phase of anterior STEMI.Methods and Results:We enrolled 1,460
consecutive patients with acute anterior STEMI. We identified an ERP-positive
group and a 1:6 propensity-matched ERP-negative group of 183 and 471,
respectively. Comparisons of sustained VT/VF, heart failure, major adverse
cardiovascular events and all-cause death were based on Kaplan-Meier survival
analysis and multivariable Cox proportional hazards regression with adjustment
for unmatched confounding factors. In our full matching propensity score cohorts,
there were 8 out of 28 variables not matching between the 2 groups. The Kaplan
Meier curves showed ERP increased the risk of sustained VT/VF in 30 days (log
rank test P=0.00065). Adjusted for baseline unmatched confounding risk, the Cox
hazards regression analysis showed sustained VT/VF was associated with the
present of ERP (hazard ratio=2.915, 95% CI: 1.520-5.588, P=0.001). CONCLUSIONS:
In a propensity score-adjusted cohort the presence of ERP had a multivariable
adjusted association with increased risk of sustained VT/VF in patients with
anterior STEMI in the early 30 days.
PMID- 28420817
TI - Association of Kidney Dysfunction With Asymptomatic Cerebrovascular Abnormalities
in a Japanese Population With Health Checkups.
AB - BACKGROUND: Cerebrovascular disease is a major cause of mortality and morbidity.
Chronic kidney disease (CKD) is prevalent in stroke patients. This study
evaluated the correlation between kidney dysfunction and asymptomatic findings on
carotid ultrasonography (US) and brain magnetic resonance imaging (MRI) in a
Japanese population with health checkups.Methods and Results:In total, 1,716
subjects aged 40-80 years, who received health checkups from January 1 to
December 31, 2015, were included. Common carotid artery intima-media thickness
(CCA-IMT) and carotid plaques by US, and the presence of old non-lacunar
infarctions, lacunar infarctions, white matter lesions (WMLs), cerebral
microbleeds (CMBs), and atrophy by brain MRI were evaluated. After adjusting for
cardiovascular risk factors, multiple regression analyses revealed that an eGFR
ranging from 15 to 44 mL/min/1.73 m2was independently associated with CCA plaques
and hypoechoic or heterogeneous plaques. Proteinuria was associated with CCA or
internal carotid artery plaques, the number of carotid plaques, and the presence
of old non-lacunar infarctions and CMBs. CONCLUSIONS: Decreased eGFR and
proteinuria were independent risk factors for asymptomatic abnormalities on
carotid US and brain MRI, which are surrogate markers for cerebrovascular
diseases. Evaluation of these abnormalities may be useful for prevention of
symptomatic cerebrovascular events in CKD patients.
PMID- 28420816
TI - Coronary Atherosclerotic Plaque Characteristics and Cardiovascular Risk Factors -
Insights From an Optical Coherence Tomography Study.
AB - BACKGROUND: The association between cardiovascular risk factors (CVRF) and the
risk of coronary events is widely acknowledged. Whether individual risk factors
may be associated with distinct plaque characteristics is currently unclear. We
investigated the relationship between CVRF and coronary plaque burden and
phenotype.Methods and Results:We assessed coronary atherosclerotic plaque
characteristics by optical coherence tomography in 67 patients with stable
coronary artery disease undergoing coronary angiography. The plaque burden and
the distinct plaque phenotypes were compared with regard to different CVRF.
Overall plaque burden was significantly greater in patients with diabetes
mellitus (P=0.010), prediabetes (P=0.035) and obesity (P=0.024), and correlated
with the number of CVRF (R=0.358, P=0.003). Patients with diabetes had a greater
extent of fibroatheroma (P=0.015), calcific fibroatheroma (P=0.031), thin-cap
fibroatheroma (TCFA-P=0.011) and plaque erosion (P=0.002). Obese patients showed
a greater extent of fibroatheroma (P=0.007), TCFA (P=0.015) and macrophage load
(P=0.043). The number of CVRF correlated with fibroatheroma (R=0.425, P<0.001),
calcific fibroatheroma (R=0.321, P=0.008), TCFA (R=0.347, P=0.004), macrophage
load (R=0.314, P=0.010) and erosion (R=0.271, P=0.029). In the multivariate
analysis, altered glycemic status and obesity were the only independent
predictors of TCFA (P=0.026 and P=0.046, respectively), whereas altered glycemic
status was the only independent predictor of plaque erosion (P=0.001).
CONCLUSIONS: Patients with diabetes, prediabetes and obesity show more extensive
coronary atherosclerosis and more vulnerable plaque phenotypes.
PMID- 28420818
TI - Tolvaptan, Is It a Trump to Worsening Renal Function?
PMID- 28420819
TI - Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases.
AB - Middle East respiratory syndrome coronavirus (MERS CoV) is a recently evolved
fatal respiratory disease that poses a concern for a global epidemic. MERS CoV
encodes 2 proteases, 3C-like protease (3CLpro) and papain-like protease (PLpro).
These proteases share in processing MERS CoV polyproteins at different sites to
yield 16 nonstructural proteins. In this work, we provide evidence that MERS CoV
3CLpro and PLpro are subject to different genetic and evolutionary influences
that shape the protein sequence, codon usage pattern, and codon usage bias.
Compositional bias is present in both proteins due to a preference for AT
nucleotides. Thymidine (T) was highly preferred at the third position of codons,
preferred and overrepresented codons in PLpro, but was replaced by guanosine (G)
in 3CLpro. Compositional constraints were important in PLpro but not in 3CLpro.
Directed mutation pressure seems to have a strong influence on 3CLpro codon
usage, which is more than 30-fold higher than that in PLpro. Translational
selection was evident with PLpro but not with 3CLpro. Both proteins are less
immunogenic by showing low CpG frequencies. Correspondence analysis reveals the
presence of 3 genetic clusters based on codon usage in PLpro and 3CLpro. Every
protein had one common cluster and 2 different clusters. As revealed by
correspondence analysis, the number of influences on codon usage are restricted
in MERS CoV 3CLpro. In contrast, PLpro is controlled by a broader range of
compositional, mutational, and other influences. This may be due to the
multifunctional protease, deubiquitination, and innate immunity suppressing
profiles of PLpro.
PMID- 28420820
TI - High insulin impaired ovarian function in early pregnant mice and the role of
autophagy in this process.
AB - Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2
diabetes mellitus), are associated with menstrual dysfunction, anovulation,
infertility, and early pregnancy loss. Ovarian dysfunction is not only related to
low pregnancy rates but also to the increased risk of miscarriage. Women with
PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian
dysfunction. In this study, we first explored whether high insulin levels
directly affected ovarian functioning during embryo implantation. Mice in the
insulin-treated group were given a subcutaneous injection of human recombinant
insulin. After insulin treatment, serum levels of E2 (estrogen), PROG
(progesterone), LH (luteinizing hormone), and FSH (follicle-stimulating hormone)
were obviously lower, and there was a significant decrement of ovarian GDF9
(growth differentiation factor 9) mRNA. H&E (hematoxylin and eosin) staining
showed a greater number of immature follicles and less luteinization in the
insulin group. Further autophagy was studied in this process. A significant
increase of P62 (SQSTM1/Sequestosome1) and a decrease of Cathepsin B, BECN1
(Beclin 1), and ULK1 (Unc-51-like kinase 1) mRNA in ovary was found in the
insulin group. Western blot analysis showed that the expressions of LC3
(microtubule-associated protein 1 light chain 3), BECN1, and Cathepsin B proteins
in ovaries from insulin group were obviously reduced, while P62 proteins were
significantly increased. All these results illustrated that insulin could
directly impair ovarian function during embryo implantation and the imbalance of
ovarian autophagy due to insulin. Autophagy could enhance the impaired ovarian
function results from insulin.
PMID- 28420821
TI - Use of liothyronine without levothyroxine in the treatment of mild consumptive
hypothyroidism caused by hepatic hemangiomas.
AB - There have been reports of the use of levothyroxine or levothyroxine plus
liothyronine for consumptive hypothyroidism caused by hepatic hemangiomas.
Administration of levothyroxine without liothyronine can be inadequate to
maintain normal levels of both free T3 and free T4 in some patients. However,
there is no report of treatment with liothyronine plus propranolol. We herein
present a case in which we used liothyronine therapy for multifocal hepatic
hemangiomas in a Japanese patient with low free T3 and normal free T4 levels. A 2
month-old Japanese male was referred to our hospital because of jaundice.
Abdominal computed tomography showed multifocal hemangiomas in both lobes of the
liver. TSH level was elevated, free T3 level was low, free T4 level was normal,
and hypothyroidism due to hepatic hemangiomas was diagnosed. In addition to
propranolol, liothyronine was started. We used liothyronine without levothyroxine
for hypothyroidism because only free T3 level had decreased, whereas free T4
level remained in the normal range. The TSH and free T3 levels normalized in this
patient in less than 1 month. The liothyronine dose was gradually reduced with
regression of the hemangiomas, and liothyronine administration was discontinued
at the age of 5 months. At the age of 11 months, growth and neurological
development of the patient met age-specific norms, and he was euthyroid at that
time. This is the first report demonstrating the use of liothyronine with
propranolol for treatment of this type of consumptive hypothyroidism.
PMID- 28420822
TI - Re-entry and related predictors among HIV-infected clients receiving methadone
maintenance treatment in Guangdong province, China.
AB - This study examined the re-entry characteristics and related predictors among HIV
infected methadone maintenance treatment (MMT) clients in Guangdong, China. Data
on HIV-infected MMT clients was obtained from the clinic MMT registration system
in Guangdong. Of the 653 participants, only 9.0% remained in the MMT program
until the end of the study. For the drop-outs, 70.0% returned to MMT at least
once by the end of the study. Re-entry was independently associated with marital
status (ORnever married = 2.24, 95% CI: 1.02-4.93; ORmarried currently = 2.34,
95% CI: 1.05-5.22), being unemployed (OR = 1.92, 95% CI: 1.12-3.27), lower
positive percentages of urine tests (OR<40% = 4.08, 95% CI: 2.21-7.54; OR40%-80%
= 2.52, 95% CI: 1.39-4.56), higher maintenance doses (OR = 3.78, 95% CI: 2.21
7.54)and poorer MMT attendance percentages (OR<20% = 282.02, 95% CI: 62.75
1268.11; OR20-49% = 20.75, 95% CI: 10.52-40.93; OR50-79% = 6.07, 95% CI: 3.44
10.73). A higher re-entry frequency was independently associated with lower
education level (ORjunior high school = 0.49, 95% CI: 0.26-0.93), average drug
use times less than twice (OR = 0.64, 95% CI: 0.41-1.00), lower positive
percentages of urine tests (OR = 0.39, 95% CI: 0.22-0.70) and poorer percentages
of MMT attendance (OR<20% = 7.24, 95% CI: 2.99-17.55; OR20-49% = 14.30, 95% CI:
5.94-34.42; OR50-79% = 6.15, 95% CI: 2.55-14.85). Re-entry and repeated re-entry
were prevalent among HIV-infected MMT clients in Guangdong, underscoring the
urgent needs of tailored interventions and health education programs for this
population.
PMID- 28420823
TI - Listeria monocytogenes serotype 4b strains replicate in monocytes/macrophages
more than the other serotypes.
AB - We analyzed the pathogenicity of various serotypes of Listeria monocytogenes
using a Balb/c mouse intravenous injection model. The survival rates of mice
inoculated with strains NS1/2b (serotype 1/2b), NS3b (serotype 3b) and NS 4b
(serotype 4b) were 60, 63.6 and 63.6%, respectively. Although the survival rates
were similar, the bacterial growth in the liver of NS3b-infected mice was 144.5
fold higher than that in the liver of NS4b-infected mice. Histopathological
analyses suggest that the NS4b strain replicated more in monocytes/macrophages,
whereas the NS3b strain replicated more in hepatocytes. These results raise a
possibility that the serotype 4b strains replicated more in monocytes/macrophages
compared to the other serotype strains. To assess this, we isolated CD11b
positive cells from mouse livers infected with EGDe (serotype 1/2a), NS1/2b,
NS3b, NS4b and the serotype 4b strains 51414 and F17 and counted the number of
live bacteria in these cells. CD11b-positive cells from the NS4b-, 51414- and F17
infected mice possessed 24.4- to 42.7-fold higher numbers of live bacteria than
those from mice infected with EGDe and NS3b strains. These results suggest that
serotype 4b strains replicated more in monocytes/macrophages than the other
serotypes, and this may be involved in the pathogenicity of serotype 4b strains,
particularly in the dissemination of L. monocytogenes through the host body.
PMID- 28420824
TI - Dynamic changes in near-infrared spectroscopy (NIRS) findings in first-episode
schizophrenia: a case report.
AB - The clinical course of schizophrenia is characterized by recurrence and
chronicity and has a large burden on society. Nevertheless, diagnosis of
schizophrenia is based only on distinctive symptoms and the disease course. Near
infrared spectroscopy (NIRS) is a useful method for measuring changes in the
hemoglobin concentration in the cortical surface area and reflects brain
function. We measured NIRS four times during the clinical course in a patient
with first-episode schizophrenia.A 17-year-old woman admitted to our hospital
because of hallucinations, delusions and appetite loss. After treatment with low
dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood
volume in the frontal region. On the basis of the clinical course of this
patient, we introduce a new point of view, namely, that NIRS findings may be
useful as a state marker that indicates the severity of schizophrenia in some
cases.
PMID- 28420825
TI - Colchicine Improves Survival, Left Ventricular Remodeling, and Chronic Cardiac
Function After Acute Myocardial Infarction.
AB - BACKGROUND: Several studies have reported that colchicine attenuated the infarct
size and inflammation in acute myocardial infarction (MI). However, the sustained
benefit of colchicine administration on survival and cardiac function after MI is
unknown. It was hypothesized that the short-term treatment with colchicine could
improve survival and cardiac function during the recovery phase of MI.Methods and
Results:MI was induced in mice by permanent ligation of the left anterior
descending coronary artery. Mice were then orally administered colchicine 0.1
mg/kg/day or vehicle from 1 h to day 7 after MI. Colchicine significantly
improved survival rate (colchicine, n=48: 89.6% vs. vehicle, n=51: 70.6%,
P<0.01), left ventricular end-diastolic diameter (5.0+/-0.2 vs. 5.6+/-0.2 mm,
P<0.05) and ejection fraction (41.5+/-2.1 vs. 23.8+/-3.1%, P<0.001), as assessed
by echocardiogram compared with vehicle at 4 weeks after MI. Heart failure
development as pulmonary edema assessed by wet/dry lung weight ratio (5.0+/-0.1
vs. 5.5+/-0.2, P<0.01) and B-type natriuretic peptide expression in the heart was
attenuated in the colchicine group at 4 weeks after MI. Histological and gene
expression analysis revealed colchicine significantly inhibited the infiltration
of neutrophils and macrophages, and attenuated the mRNA expression of pro
inflammatory cytokines and NLRP3 inflammasome components in the infarcted
myocardium at 24 h after MI. CONCLUSIONS: Short-term treatment with colchicine
successfully attenuated pro-inflammatory cytokines and NLRP3 inflammasome, and
improved cardiac function, heart failure, and survival after MI.
PMID- 28420827
TI - Relaxin and Matrix Metalloproteinase-9 in Angiotensin II-Induced Abdominal Aortic
Aneurysms.
AB - BACKGROUND: This study determined whether relaxin or matrix metalloproteinase
(MMP)-9 influences angiotensin II (AngII)-induced abdominal aortic aneurysms
(AAA).Methods and Results:Male C57BL/6 or apolipoprotein E-/-mice were infused
with AngII with or without relaxin. Relaxin did not influence AngII-induced AAA
in either mouse strain. Infusion of AngII reduced, but relaxin increased, MMP-9
mRNA in macrophages. We then determined the effects of MMP-9 deficiency on AAA in
apolipoprotein E-/-mice. MMP-9 deficiency led to AAA formation in the absence of
AngII, and augmented AngII-induced aortic rupture and AAA incidence. CONCLUSIONS:
MMP-9 deficiency augmented AngII-induced AAA.
PMID- 28420826
TI - Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor
Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension.
AB - BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor)
agonist with a non-prostanoid structure. In this open-label Phase II trial, the
efficacy and safety of selexipag in Japanese patients with pulmonary arterial
hypertension (PAH) is examined.Methods and Results:Selexipag was administered at
200 MUg twice daily and titrated up to 1,600 MUg by increments of 200 MUg in 37
subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33
patients comprising the per-protocol set, the pulmonary vascular resistance (PVR;
primary endpoint) decreased from 683.2+/-237.3 to 560.3+/-238.7
dyn.s/cm5(P<0.0001). For the secondary endpoint, the 6-min walk distance (6MWD)
increased from 445.0+/-102.2 to 459.1+/-112.8 m (P=0.0324); World Health
Organization functional class improved in 4 patients (12.1%), and was maintained
in 29 patients (87.9%). A decrease in PVR was also shown in patients treated with
selexipag, on top of a phosphodiesterase inhibitor and endothelin receptor
antagonist. Most of the commonly reported adverse events were consistent with
those reported for other PGI2formulations. Thirty-four patients attained the
individual maximum tolerated dose (maintenance dose). CONCLUSIONS: The efficacy
and tolerability of selexipag in Japanese PAH patients was confirmed by
improvement in pulmonary hemodynamics, exercise capacity, symptoms. Selexipag is
an efficacious treatment option for Japanese PAH patients. (Trial registration:
JAPIC Clinical Trials Information [JapicCTI-111532].).
PMID- 28420828
TI - Y-TZP zirconia regeneration firing: Microstructural and crystallographic changes
after grinding.
AB - This study evaluated microstructural and crystallographic phase changes after
grinding (G) and regeneration firing/anneling (R) of Y-TZP ceramics. Thirty five
bars (LavaTM and Ice Zirkon) were divided: Y-TZP pre-sintered, control (C),
regeneration firing (R), dry grinding (DG), dry grinding+regeneration firing
(DGR), wet grinding (WG) and wet grinding+regeneration firing (WGR). Grinding was
conducted using a diamond bur and annealing at 1,000 degrees C. The
microstructure was analyzed by SEM and the crystalline phases by X-ray
diffraction (XRD). XRD showed that pre-sintered specimens contained tetragonal
and monoclinic phases, while groups C and R showed tetragonal, cubic and
monoclinic phases. After grinding, the cubic phase was eliminated in all groups.
Annealing (DGR and WGR) resulted in only tetragonal phase. SEM showed semi
circular cracks after grinding and homogenization of particles after annealing.
After grinding, surfaces show tetragonal and monoclinic phases and R can be
assumed to be necessary prior to porcelain layering when grinding is performed.
PMID- 28420829
TI - Bonding measurement -Strength and fracture mechanics approaches.
AB - This study investigated the effect of cross-sectional areas on interfacial
fracture toughness and bond strength of bilayered dental ceramics. Zirconia core
ceramics were veneered and cut to produce specimens with three different cross
sectional areas. Additionally, monolithic specimens of glass veneer were also
prepared. The specimens were tested in tension until fracture at the interface
and reported as bond strength. Fracture surfaces were observed, and the apparent
interfacial toughness was determined from critical crack size and failure stress.
The results showed that cross-sectional area had no effect on the interfacial
toughness whereas such factor had a significant effect on interfacial bond
strength. The study revealed that cross-sectional area had no effect on the
interfacial toughness, but had a significant effect on interfacial bond strength.
The interfacial toughness may be a more reliable indicator for interfacial bond
quality than interfacial bond strength.
PMID- 28420831
TI - Enamel microcracks in terms of orthodontic treatment: A novel method for their
detection and evaluation.
AB - The study aimed at introducing current available techniques for enamel
microcracks (EMCs) detection, and presenting a method for direct quantitative
analysis of an individual EMC. Measurements of the detailed EMCs characteristics
(location, length, and width) were taken from the reconstructed images of the
buccal tooth surface (teeth extracted from two age groups of patients) employing
a scanning electron microscopy (SEM) and our derived formulas before and after
ceramic brackets removal. Measured parameters of EMCs for younger age group were
2.41 um (width), 3.68 mm (length) before and 2.73 um, 3.90 mm after debonding;
for older -4.03 um, 4.35 mm before and 4.80 um, 4.37 mm after brackets removal.
Following debonding EMCs increased for both groups, however the changes in width
and length were statistically insignificant. Regardless of the age group,
proposed method enabled precise detection of the same EMC before and after
debonding, and quantitative examination of its characteristics.
PMID- 28420830
TI - Antimicrobial and antibiofilm activities of MTA supplemented with bismuth
lipophilic nanoparticles.
AB - The objective of this work was to determine the antimicrobial and antibiofilm
properties of mineral trioxide aggregate (MTA) supplemented with bismuth
lipophilic nanoparticles (BisBAL NPs). The antimicrobial activity of the
composite MTA-BisBAL NPs was determined by the disk diffusion assay, while
antibiofilm activity was analyzed by fluorescence microscopy. The cytotoxicity of
MTA-BisBAL NPs was determined on human gingival fibroblasts by optical microscopy
and crystal violet staining. MTA-BisBAL NPs inhibited the growth of Enterococcus
faecalis, Escherichia coli, and Candida albicans and also detached the biofilm of
fluorescent E. faecalis after 24 h of treatment. The addition of BisBAL
nanoparticles did not significantly modify the physical properties of MTA, and
cytotoxicity was not observed when MTA-BisBAL NPs was added on human gingival
fibroblasts. Altogether these results suggest that BisBAL nanoparticles provide
antimicrobial and antibiofilm activities to MTA while it retained their
biophysical properties without cause side effects on human gingival fibroblasts.
PMID- 28420832
TI - Effect of air-particle pressures on the surface topography and bond strengths of
resin cement to the hybrid ceramics.
AB - This study aimed to determine the appropriate pressure for airborne-abrasion by
comparing the shear bond strength values for different hybrid ceramic surfaces.
Two materials were used to produce hybrid ceramic specimens: Lava Ultimate and
MAZIC Duro. The group of specimens whose surfaces were not subjected to airborne
abrasion was set as the control group. In the experimental group, airborne
abrasion was performed at pressures of 0.1, 0.2, and 0.3 MPa. After the adhesive
and resin cement was applied, an SBS test was performed. For the MAZIC Duro
block, the SBS increased monotonically with the airborne-abrasion pressure
increased, peaking at 0.3 MPa. For the Lava Ultimate block, the SBS increased as
the airborne-abrasion pressure increased to 0.2 MPa, and then decreased in the
0.3-MPa group, thereby peaking at 0.2 MPa. This study has confirmed that the
bonding strength varies with the material used even when applying the same
surface treatment.
PMID- 28420833
TI - Correlations among bending test methods for dental hard resins.
AB - Three types of bending tests -the 3-point bending test, 4-point bending test and
biaxial flexural test- were performed to examine the correlations among the
testing methods for dental hard resins (HRs). The results for 5 HRs showed that
the bending strengths in descending order were: biaxial flexural strength>3-point
bending strength>4-point bending strength. Regression analysis of the test
methods indicated that the coefficients of determination were large for all test
methods; the largest was for the combination of the 4-point bending test and
biaxial flexural tests. The Weibull moduli ranged from 5.42 to 10.61, and a
similar descending-order trend was found in the Weibull characteristic strength
(S0) of the test methods. The biaxial flexural test method is thus a valid test
of the flexural strength of dental hard resins.
PMID- 28420834
TI - Improving the efficacy of chlorhexidine-releasing elastomerics using a layer-by
layer coating technique.
AB - The aims of this study were to identify the optimal concentration of coated
orthodontic elastomerics using a layer-by-layer technique that can release
chlorhexidine (CHX) as an antimicrobial material, and to measure the physical
properties and antimicrobial effects of the coated elastomerics. Ethyl cellulose
(EC) was used as the polymer, and five study groups with various combinations of
solvents (i.e., ethanol and dichloromethane [DCM]) were included. The coated
elastomerics were evaluated with a spectrophotometer to confirm the release of
CHX, and their surfaces were observed by SEM. The CHX+EC+DCM group sustained
antimicrobial release for the longest period (168 h, p<0.001) and exhibited the
largest antimicrobial effect in an inhibition zone test using S. mutans for 7
days (p<0.05). This group had most effective physical properties and
antimicrobial effects of coated elastomerics produced using a layerby-layer
technique, and so its composition should be considered for use in clinical
applications in orthodontics.
PMID- 28420835
TI - Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese
Patients with Type 2 Diabetes Mellitus: The Dogo Study.
AB - Objective Macrovascular diseases and urgency incontinence are common among
Japanese patients with type 2 diabetes mellitus. However, little evidence exists
regarding the association between stroke and urgency incontinence among patients
with type 2 diabetes mellitus. We examined the associations between macrovascular
complications and urgency incontinence among Japanese patients with type 2
diabetes mellitus. Methods The study subjects were 818 Japanese patients with
type 2 diabetes mellitus. Urgency incontinence was defined as present when a
subject answered "once a week or more" to the question: "Within one week, how
often do you leak urine because you cannot defer the sudden desire to urinate?"
We adjusted our analyses for sex, age, body mass index, duration of type 2
diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated
hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral
neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was
independently positively associated with urgency incontinence, with an adjusted
odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between
ischemic heart disease or peripheral artery disease and the prevalence of urgency
incontinence were not significant. Conclusion In Japanese patients with type 2
diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery
disease, was independently positively associated with urgency incontinence.
PMID- 28420836
TI - High Detection Rates of Urine Mycobacterium tuberculosis in Patients with
Suspected Miliary Tuberculosis.
AB - Objective The utility of detecting Mycobacterium tuberculosis in urine samples
from patients with pulmonary tuberculous with diffuse small nodular shadows
(suspected miliary tuberculosis (MTB)) is still unclear in Japan. A retrospective
cross-sectional study was conducted to investigate the detection rates of M.
tuberculosis in urine of patients with suspected MTB. Methods Among 687
hospitalized patients with tuberculosis, 45 with culture-confirmed suspected MTB
and the data of culture and polymerase chain reaction (PCR) for M. tuberculosis
in urine and sputum samples were investigated. The detection rates of M.
tuberculosis in urine using cultures and PCR were calculated. The detection rate
of urine was then compared with that of bone marrow aspiration. Results Fourteen
patients with suspected MTB were ultimately analyzed. A diagnosis of miliary
tuberculosis was suspected in all patients before anti-tuberculosis chemotherapy.
Positive results by PCR (11 [78.6%] cases) and culture (8 [57.1%]) were obtained
from urine samples. In patients with suspected MTB, there was no significant
difference in the detection rates between M. tuberculosis in urine using a
combination of PCR and culture (85.6% [12/14 cases]) and bone marrow aspiration
(66.7% [8/12 cases]) (p>0.05). Conclusion Using PCR and culture, we demonstrated
high detection rates of M. tuberculosis in the urine of patients with suspected
MTB. A combination of PCR and culture compared favorably with the detection rates
achieved with bone marrow aspiration. We believe that detection of M.
tuberculosis from urine and sputum samples may be easy and safe for patients with
disseminated tuberculosis infections such as definitive MTB.
PMID- 28420837
TI - Clinical Characteristics of Rheumatoid Arthritis Patients Achieving Functional
Remission with Six Months of Biological DMARDs Treatment.
AB - Objective Although previous studies have reported the prognostic factors for
functional remission, no reports have cited the predictive factors. Our aim was
to study the predictive factors for functional remission, which is a treatment
goal in rheumatoid arthritis (RA), after receiving biological disease-modifying
antirheumatic drugs (bDMARDs) treatment for six months. Methods The study
consisted of 333 RA patients treated with bDMARDs for six months. The following
patient characteristics were investigated: age, gender, disease duration, type of
bDMARDs, baseline steroid and methotrexate dosage, and levels of serum rheumatoid
factor, matrix metalloprotease, anti-cyclic citrullinated peptides antibody,
tumor necrosis factor-alpha, and interleukin-6. In our evaluation, we used the
Simplified Disease Activity Index (SDAI) for RA disease activity, health
assessment questionnaire disability index (HAQ-DI) for activity of daily living,
Short Form (SF)-36 for quality of life, and Hamilton Depression Rating Scale (HAM
D) or Self-rating Depression Scale (SDS) to determine the patients' depression
status. The subjects were divided into two groups: patients with HAQ-DI<=0.5 and
HAQ-DI>0.5 at 6 months. Results A univariate analysis comparing a group of RA
patients without functional remission (n=68) showed that the patients with
functional remission (n=164) had the following in common compared with those
without remission: younger age, shorter disease duration, lower baseline steroid
dosage, lower SDAI, lower HAQ-DI, higher SF-36, and lower HAM-D. Only lower HAQ
DI scores and "mental health" score on the SF-36 were detected using a logistic
regression analysis. Conclusion These findings suggested that RA patients with
lower HAQ-DI and lower depression scores at baseline were more likely to achieve
functional remission using bDMARDs treatment than those without these variables.
PMID- 28420839
TI - Solitary Gastric Metastasis from a Stage IA Serous Ovarian Carcinoma: A Case
Report with Literature Review.
AB - Gastric metastasis from ovarian cancer is exceptionally rare and generally occurs
in advanced stages. A 71-year-old woman presented with a solitary gastric
submucosal mass 8 years after the diagnosis of a stage IA ovarian serous
adenocarcinoma. Endoscopy showed a tumor covered with normal gastric mucosa.
Initially, a gastrointestinal stromal tumor was suspected, but biopsy revealed a
histology of invasive micropapillary carcinoma, similar to the histological
findings of the previously resected ovarian tumor. Clinicians should consider
that in patients with a submucosal tumor and a history of ovarian cancer, gastric
lesions may be secondary metastases from ovarian cancer.
PMID- 28420838
TI - Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy
confirmed Dementia.
AB - Objective A better understanding of risk factors for pneumonia-caused death may
help to improve the clinical management of dementia. Methods A retrospective
observational study was conducted by reviewing the medical charts and autopsy
reports of 204 patients who were admitted to hospital, underwent a post-mortem
examination, and who were neuropathologically diagnosed with dementia. The risk
factors for pneumonia-caused death were examined both as underlying and immediate
causes of death using logistic regression models. Results A high frequency of
pneumonia-caused death was observed both in underlying- (37.3%) and immediate-
(44.1%) cause of death, but varied according to the subtypes of dementia. The
factors related to pneumonia-caused death (underlying) were subtypes of dementia;
Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459
5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and
progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia
(OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180
8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026
0.861). Factors relating to pneumonia-caused death (immediate) were incidence of
pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male
(OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm
(OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to
the pneumonia-caused death were evaluated depending on whether pneumonia was the
underlying- or immediate-cause of death. Strengthening clinical management on
dysphagia and diabetes mellitus, and preventing incidence of pneumonia during
hospitalization appear to be the important for the terminal stage of hospitalized
patients with dementia.
PMID- 28420840
TI - Successful Long-term Management with a Single Administration of Tri-weekly Nab
paclitaxel in a Patient with Advanced Gastric Cancer with Peritoneal
Dissemination.
AB - Nanoparticle albumin-bound (nab)-paclitaxel has shown promising activity in
advanced gastric cancer treatment. We herein report a case of advanced gastric
cancer involving long-term management with a single administration of nab
paclitaxel. A 71-year-old man diagnosed with advanced gastric cancer with
malignant ascites was treated with nab-paclitaxel as a second-line chemotherapy.
He refused treatment continuation because of various severe toxicities in the
first treatment cycle; he was therefore followed-up without any further
treatments. Despite this, no disease progression was observed over 9 months.
After progression, he received dose-dense paclitaxel, but he did not respond to
this treatment and eventually died.
PMID- 28420841
TI - Tranexamic Acid Controlled Chronic Disseminated Intravascular Coagulation
Associated with Aortic Dissection and Patent False Lumen for Three Years.
AB - The management of chronic disseminated intravascular coagulation (DIC) caused by
aortic dissection has not yet been established. Even in cases where surgical
correction is performed, therapeutic control of systemic hemorrhaging is still
required. We herein report the successful treatment of a case of aortic
dissection with a patent false lumen using tranexamic acid for acute exacerbation
of chronic DIC. Oral administration of 1,500 mg tranexamic acid per day
stabilized the coagulative and fibrinolytic parameters and relieved bleeding
tendencies with no side effects. Heparin was administered periodically for the
management of hemodialysis. This favorable result continued for up to 3 years.
PMID- 28420842
TI - The Development of Marked Collateral Circulation due to Inferior Vena Cava Filter
Occlusion in a Patient with Chronic Thromboembolic Pulmonary Hypertension
Complicated with Anti-phospholipid Syndrome.
AB - A 30-year-old Japanese man was diagnosed with chronic thromboembolic pulmonary
hypertension (CTEPH) with lupus anticoagulants (LAs) in 2003. He underwent
pulmonary endarterectomy after the placement of an inferior vena cava filter
(IVCF) in 2004, and treatment with warfarin was continued. In 2014, IVCF
occlusion and marked collateral circulation were noted during an examination for
transient dyspnea; however, his warfarin level was within the therapeutic range
for 88.9% of the time from 2003 to 2014. We herein report a rare case of CTEPH
and LAs with IVCF occlusion; in such cases, intense treatment may be required.
PMID- 28420843
TI - Rosai-Dorfman Disease of the Lung Overlapping with IgG4-related Disease: The
Difficulty in Its Differential Diagnosis.
AB - We herein report a case of Rosai-Dorfman disease (RDD) overlapping with IgG4
related disease (IgG4-RD), which presented as diffuse interstitial lung disease
with a perilymphatic pattern, followed by submandibular gland and eyelid
swelling. The pathological findings of the submandibular gland biopsy specimen
were indicative of IgG4-RD alone. We diagnosed the patient with RDD with
overlapping IgG4-RD. However, the optimal method for differentiating between
these two entities is still controversial. It is important that clinicians are
aware that RDD should be included in the differential diagnoses of diffuse
interstitial lung disease with a perilymphatic pattern and that RDD can overlap
with IgG4-RD.
PMID- 28420844
TI - Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia
Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.
AB - This report describes two patients with sporadic lymphangioleiomyomatosis
complicated by protein-losing enteropathy (PLE). Imaging studies indicated
retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive
tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one
patient; whereas the site in the other patient was intestinal. Treatment with
sirolimus led to the complete resolution of PLE within several months;
additionally, marked shrinkage was observed in the lymphangioleiomyomas of both
cases. These findings suggest that colonic or intestinal lymphatic congestion due
to neighboring lymphangioleiomyomas was the mechanism for the development of PLE.
At the time of writing this report, the beneficial effect of sirolimus has lasted
for more than 3 years.
PMID- 28420845
TI - Suffocation due to Thoracic Deformity Caused by Acromegaly.
AB - A 61-year-old man with gigantism and acromegaly choked and fell into a coma.
Immediate tracheal intubation resulted in a return of his consciousness. Enhanced
computed tomography indicated that the trachea and left main bronchus were
compressed by the thoracic spine and sternum. He required tracheotomy and
positive end-expiratory pressure to maintain his pulmonary function. This is the
first case of suffocation due to a thoracic deformity associated with acromegaly.
Physicians should focus on clearing the tracheal airway using computed tomography
to elucidate the anatomical relationship between the trachea and surrounding
structures in acromegalic patients suffering from dyspnea.
PMID- 28420846
TI - Intrathecal Isoniazid for Refractory Tuberculous Meningitis with Cerebral
Infarction.
AB - A 30-year-old Vietnamese woman, about 19 weeks pregnant, was admitted for acute
cerebral infarction with stenosis of the left middle cerebral artery (LMCA),
tuberculous meningitis, and miliary tuberculosis. Treatment with heparin,
quadruple anti-tuberculosis therapy, and dexamethasone afforded prompt
symptomatic improvement. However, she delivered a stillbirth, after which there
was recurrence of acute cerebral infarction with LMCA occlusion, sinus
thrombosis, and cranial base inflammation. A thrice-weekly 100 mg dose of
intrathecal isoniazid (INH) improved the signs of meningeal inflammation. The
patient was discharged ambulatory after 7 months. In refractory tuberculous
meningitis, multimodal therapy with intrathecal INH and steroids should be
considered.
PMID- 28420847
TI - The Successful Treatment of Myeloperoxidase Antineutrophil Cytoplasmic Antibody
positive Hypertrophic Pachymeningitis in Patients with the Limited Form of
Granulomatosis with Polyangiitis Using Methotrexate: Two Case Reports.
AB - Recent findings have indicated a close relationship between myeloperoxidase
antineutrophil cytoplasmic antibody (MPO-ANCA)-positive hypertrophic
pachymeningitis and the limited form of granulomatosis with polyangiitis (GPA).
In Japan, MPO-ANCA-positive hypertrophic pachymeningitis predominantly occurs in
elderly individuals. We herein describe the cases of two patients with MPO-ANCA
positive hypertrophic pachymeningitis associated with the limited form of GPA who
were successfully treated with a combination of corticosteroids and methotrexate.
Although methotrexate has been shown to be less effective than cyclophosphamide
for inducing the remission of GPA in patients with organ-threatening diseases,
its safety and efficacy may make it a useful alternative treatment modality for
patients with the limited form of GPA who show meningeal involvement.
PMID- 28420849
TI - The Effective Treatment of Lung Infection Due to Scedosporium prolificans with
Voriconazole and Surgery.
AB - Scedosporium prolificans is a fungus that has demonstrated resistance against
most currently available antifungal agents and which causes a rapidly
disseminating and potentially fatal infection. A 68-year-old woman presented with
a fever and consolidation in the lung field. Her symptoms and inflammatory
reaction did not improve despite treatment with tazobactam/piperacillin,
meropenem, and micafungin. Scedosporium prolificans was detected from the
patient's bronchial lavage fluid, and we initiated treatment with voriconazole.
Voriconazole was effective in shrinking the consolidation and suppressing the
inflammatory reaction. The residual lesion was surgically resected because of the
risk of systemic dissemination. The patient is currently alive without relapse or
dissemination.
PMID- 28420848
TI - Myositis Ossificans of the Hip Due to Pyogenic Arthritis Caused by Campylobacter
fetus Subspecies fetus.
AB - A 61-year-old woman was admitted with severe hip pain causing immobility and high
serum levels of inflammatory markers. The patient had a medical history of
diabetes. She had been scheduled to undergo right hip replacement surgery for the
treatment of osteoarthritis associated with gradually progressive pain. On
admission, an enhanced abdominal computed tomography scan showed an abnormal
increase in synovial fluid surrounding the right ilium, with piriformis muscle
calcification. Subsequent blood and specimen cultures identified Campylobacter
fetus subspecies fetus. This is a rare report of a case of myositis ossificans
followed by C. fetus pyogenic arthritis of the hip.
PMID- 28420850
TI - Alert Regarding Cisplatin-induced Severe Adverse Events in Cancer Patients with
Xeroderma Pigmentosum.
AB - Xeroderma pigmentosum (XP) is a genetic disease in which DNA repair mechanisms
are impaired. Cisplatin (CDDP) exerts cytotoxic effects by forming mainly
intrastrand DNA cross-links, and sensitivity to CDDP depends on the DNA repair
system. Several in vitro studies have suggested that treatment with CDDP may
cause enhanced adverse events as well as anti-tumor activity in cancer patients
with XP. This article is the first to describe two cancer patients with XP
showing severe adverse events following CDDP-based chemotherapy. Physicians
should pay attention when administering CDDP in cancer patients with XP.
PMID- 28420851
TI - Left Paraduodenal Hernia with Bowel Strangulation.
PMID- 28420852
TI - Pulmonary Sarcoidosis Presenting with Thin-walled Small Cysts.
PMID- 28420853
TI - Sarcomatoid Carcinoma Mimicking Malignant Mesothelioma.
PMID- 28420854
TI - Transient Splenial Lesion Following Abrupt Withdrawal of Carbamazepine.
PMID- 28420855
TI - Fasting Hypoglycemia on 18F-FDG PET/CT Scan.
PMID- 28420856
TI - Fasting plasma glucose and body mass index during the first trimester of
pregnancy as predictors of gestational diabetes mellitus in a Chinese population.
AB - This retrospective study assessed fasting plasma glucose (FPG) and body mass
index (BMI) during the first trimester of pregnancy as potential screening
indicators of later gestational diabetes mellitus (GDM). The study population
included 820 pregnant women who delivered in our hospital between 17 September
2013 and 3 March 2014. Demographics and baseline characteristics were collected
at the first antenatal visit; FPG levels were measured at 8 or 9 weeks. All
participants underwent a 75-g oral glucose tolerance test at 24-28 weeks
gestation. Multivariate logistic regression and receiver operating characteristic
curve analysis were performed to determine the diagnostic power of risk factors.
GDM was diagnosed in 20.3% of the women. There was an increased prevalence of GDM
with advancing age, parity, high FPG, and obesity, but not in women with family
predisposition. FPG (OR: 3.984; 95% CI: 2.397-6.62) and BMI (OR: 1.144; 95% CI:
1.083-1.208) were independent risk factors for later development of GDM (p<0.01).
FPG level >=4.6 mmol/L was the best threshold for predicting GDM with a
sensitivity of 53.89 and specificity of 70.90%. BMI >=23.5 kg/m2 yielded a
sensitivity of 48.5% and a specificity of 73.1% for predicting GDM. FPG and BMI
combined markedly enhanced the predictive capability for GDM (OR, 3.861; 95% CI:
2.701-5.520). High FPG or BMI in the first trimester, especially in combination,
may predict later GDM with limited accuracy and specificity in Chinese women.
PMID- 28420857
TI - Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes
insipidus in the third trimester of pregnancy.
AB - We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in
the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma
osmolality (300 mOsm/kgH2O) and low urinary osmolality (92 mOsm/kgH2O) were
observed at the admission to our hospital. Plasma arginine vasopressin (AVP)
level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality.
Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine
osmolality increased in response to desmopressin. The diagnosis of central
diabetes insipidus was made from these results. Magnetic resonance imaging (MRI)
of hypothalamic-pituitary region demonstrated a significant enlargement of the
pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti
rabphilin-3A antibodies that have been recently reported as a biomarker of
lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus
continued after delivery, suggesting that polyuria was not mainly due to
excessive vasopressinase activity or reduced renal sensitivity to AVP by
prostaglandin E2 that can cause temporal polyuria during pregnancy. We therefore
clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo
neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy.
This case suggested the usefulness of anti-rabphilin-3A antibodies for the
etiological diagnosis of central diabetes insipidus during pregnancy.
PMID- 28420858
TI - Transcriptional regulation of pancreas development and beta-cell function
[Review].
AB - A small number of cells in the adult pancreas are endocrine cells. They are
arranged in clusters called islets of Langerhans. The islets make insulin,
glucagon, and other endocrine hormones, and release them into the blood
circulation. These hormones help control the level of blood glucose. Therefore, a
dysfunction of endocrine cells in the pancreas results in impaired glucose
homeostasis, or diabetes mellitus. The pancreas is an organ that originates from
the evaginations of pancreatic progenitor cells in the epithelium of the foregut
endoderm. Pancreas organogenesis and maturation of the islets of Langerhans
occurs via a coordinated and complex interplay of transcriptional networks and
signaling molecules, which guide a stepwise and repetitive process of the
propagation of progenitor cells and their maturation, eventually resulting in a
fully functional organ. Increasing our understanding of the extrinsic, as well as
intrinsic mechanisms that control these processes should facilitate the efforts
to generate surrogate beta cells from ES or iPS cells, or to reactivate the
function of important cell types within pancreatic islets that are lost in
diabetes.
PMID- 28420859
TI - Ultrastructural and physico-chemical characterization of saliva during menstrual
cycle in perspective of ovulation in human.
AB - Human saliva is a potential diagnostic fluid and any alteration in body might be
reflected in saliva so that saliva is considered as "mirror of the body".
Variations in salivary hormone level, ultra structure, pH, flow rate, buffering
capacity and electrolytes level are found during menstrual cycle in regard to
ovulation. Thirty healthy volunteers were used for the assessment of physico
chemical changes in saliva. Reproductive cycle was categorized as pre-ovulation
phase (5 to 12 days), ovulation phase (13 or 14 days) and post-ovulation phase
(15 to 25 days) according to salivary arborization test and hormonal analysis.
Estradiol and luteinizing hormone was gradually increased and attained peak at
the level of 2.28 +/- 0.20 pg/mL and 1.35 +/- 0.41 mIU/mL respectively during the
ovulation phase. The electrolytes result clearly indicates that the influx of
common electrolytes is important for crystallization and help to induce clear
ferning pattern in ovulation phase. Sodium (Na) and chloride (Cl) were found to
be high during ovulation phase only. Average salivary pH was 7.5, 7.1, and 7.3
during ovulation, pre- and post-ovulation phases respectively. Buffering capacity
of saliva was normal during pre- and post- ovulation phases. In contrast, in
ovulation phase the buffer capacity was slightly higher. At the first time, the
scanning electron microscopy (SEM) studies revealed the ultra structure
difference of saliva during menstrual cycle. During ovulation phase a compact
network-shaped mesh was appeared; such structure was not appeared in pre- and
post ovulation phases. Additionally, we observed the saliva is arrayed as a fine
mosaic-like structure during ovulation. Based on physico-chemical properties and
hormonal levels may lead to develop a detection kit/sensor for detecting the
ovulation phase in human.
PMID- 28420861
TI - Potential proteins targeted by let-7f-5p in HeLa cells.
AB - MicroRNAs are a class of small, endogenous, non-coding RNAs mediating
posttranscriptional gene silencing. The current authors hypothesized that let-7f
5p is likely involved in cell invasion and proliferation by regulating the
expression of target genes. The current study combined let-7f-5p with iTRAQ to
assess its effect on gene expression in HeLa cells. Results indicated that 164
proteins were expressed at different levels in HeLa cells overexpressing let-7f
5p and negative controls and that 172 proteins were expressed at different levels
in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that
let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1
(IGF2BP1) in HeLa cells.
PMID- 28420860
TI - Comparison of the docetaxel concentration in human plasma measured with liquid
chromatography-tandem mass spectrometry (LC-MS/MS) and a nanoparticle immunoassay
and clinical applications of that assay.
AB - To determine the feasibility of using a nanoparticle immunoassay for clinical
therapeutic drug monitoring (TDM) of docetaxel concentrations, a sensitive and
simple method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was
established to measure the docetaxel concentration in human plasma and the
results of LC-MS/MS and the immunoassay were compared. Docetaxel and paclitaxel
(the internal standard, or IS) in human plasma were extracted through protein
precipitation, separated on a Diamonsil C18 column (150 mm * 4.6 mm, 5 MUm),
ionized with positive ions, and detected with LC-MS/MS in multi-reaction
monitoring (MRM) mode. Plasma samples from 248 cancer patients were assayed with
LC-MS/MS and a nanoparticle immunoassay. Data from the samples were analyzed with
the statistical software SPSS and the software MedCalc. Results indicated that
the calibration curve of the validated method of LC-MS/MS was linear over the
range of 10-2,000 ng/mL, with an lowest limit of quantitation (LLOQ) of 10 ng/mL,
and the intra- and inter- day precision and accuracy were both < +/- 15%.
Comparison of the two methods indicated that results of the LC-MS/MS were closely
related to those of the nanoparticle immunoassay, with a correlation coefficient
(R) of 0.965 and acceptable 95% confidence intervals (CI) of - 231.7-331.1 ng/mL.
Overall, the established method of LC-MC/MS and the nanoparticle immunoassay were
both suitable for measurement of the docetaxel concentration in human plasma, and
the immunoassay was far more cost-effective and better at clinical TDM of
docetaxel in clinical practice.
PMID- 28420862
TI - Clinical characteristics, treatment, and prognosis of patients with ischemic and
nonischemic acute severe heart failure. Analysis of data from the COMMIT-AHF
registry.
AB - INTRODUCTION There are limited data on the impact of ischemic etiology on the
clinical status and long-term prognosis of patients with acute severe heart
failure (HF) not associated with acute coronary syndrome (ACS). OBJECTIVES The
aim of this study was to assess the clinical characteristics, treatment, and 12
month mortality of patients with acute severe HF not associated with ACS,
according to the etiology of HF. PATIENTS AND METHODS Data from 112 patients
with acute severe HF not associated with ACS were analyzed: 61 patients with
ischemic HF and 51 patients with nonischemic HF. Acute severe HF was defined as
acute HF on admission with at least one of the following characteristics:
pulmonary congestion, cardiogenic shock, catecholamine or intraaortic balloon
pump support, ultrafiltration, mechanical ventilation, prolonged use of
intravenous diuretics, fluid in the body cavities requiring decompression, or
multiorgan failure. RESULTS Patients with ischemic HF were older (62 vs 54 years,
P = 0.001), predominately male (84% vs 65%, P = 0.02), had more comorbidities,
and had lower left ventricular ejection fraction (21% vs 27%, P = 0.02). There
were no significant differences in treatment modalities (ie, mechanical
ventilation, hemodiafiltration, intraaortic balloon pump, left ventricular assist
device, heart transplantation), except for 14 percutaneous coronary interventions
in the ischemic group. In-hospital adverse events were similar between the
groups. Among 83 discharged patients with available follow-up, death was reported
for 15 patients with ischemic and 11 patients with nonischemic HF (34% vs 28%, P
= 0.42). CONCLUSIONS Ischemic HF, accounting for approximately half of the cases
of acute severe HF not related to ACS, was not associated with a significantly
worse prognosis than nonischemic HF.
PMID- 28420863
TI - Changes in systemic immune response after stereotactic ablative radiotherapy.
Preliminary results of a prospective study in patients with early lung cancer.
AB - INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common lung tumor.
Conventional conservative treatment in medically inoperable patients with early
stage NSCLC has poor outcome. To improve treatment efficacy, stereotactic
ablative radiotherapy (SABR) has been developed, which enables the delivery of
high-dose radiation to the tumor. OBJECTIVES This prospective study was
conducted to test the hypothesis that a sudden death of cancer cells after SABR
may lead to changes in systemic immune response. PATIENTS AND METHODS We
enrolled 89 treatment-naive patients with stage T1/2aN0 NSCLC. All patients
received SABR, in accordance with treatment standards at our department. Blood
samples were collected 3 times: before treatment (n = 89), and then at 2 (n = 86)
and 12 weeks (n = 75) after treatment completion to assess the proportion of
CD4(+) and CD8(+) T cells, and the expression of T-lymphocyte transcription
factors: T-bet, GATA-3, ROR-gammat, and FoxP3. Serum C-reactive protein (CRP)
levels, absolute neutrophil count (ANC), absolute lymphocyte count, and white
blood cell (WBC) count were measured to exclude the impact of nonspecific
inflammatory reaction. The expression levels of lymphocyte antigens were measured
by flow cytometry. RESULTS Serum CRP levels, ANC, and WBC count remained
stable during the study. We observed slight lymphopenia, which correlated with
irradiated lung volume. After SABR, the proportion of CD8(+), CD4(+), as well as
the proportion of CD4(+) T cells expressing GATA-3(+), T-bet(+), or ROR-gammat(+)
increased, while the number of CD4(+)FoxP3(+) cells (specific for regulatory T
cells) decreased. CONCLUSIONS Our findings may suggest that SABR enhances the
systemic immune response by increasing the proportion of proinflammatory T-cell
subpopulations.
PMID- 28420865
TI - A Novel Variant t(1;22) Translocation - ins(22;1)(q13;p13p31) - in a Child with
Acute Megakaryoblastic Leukemia.
AB - BACKGROUND The reciprocal translocation t(1;22)(p13;q13) involving the RBM15 and
MKL1 genes is an uncommon abnormality that occurs in a subset of acute myeloid
leukemia with megakaryocytic differentiation (AMKL). Variant translocations have
been infrequently described in this subtype of leukemia. CASE REPORT We describe
the case of a 3-month-old girl who presented with progressive abdominal
distension, vomiting, and fever. Although there was no morphologic evidence of
leukemia in the bone marrow, cytogenetic and metaphase fluorescence in situ
hybridization analysis identified an insertion of p13p31 bands of chromosome 1
onto the long arm of chromosome 22, resulting in the karyotype:
46,XX,ins(22;1)(q13;p13p31). Subsequent liver biopsy demonstrated extensive
involvement by AMKL. CONCLUSIONS AMKL can present with fewer than 20% blasts in
the peripheral blood or bone marrow, necessitating careful evaluation for
extramedullary disease. In other situations, bone marrow fibrosis can result in
difficult marrow aspirations and a falsely decreased blast count. This case
report highlights the critical role of careful cytogenetic and FISH testing in
the diagnosis of AMKL.
PMID- 28420864
TI - Insulin Growth Factor 1 Protects Neural Stem Cells Against Apoptosis Induced by
Hypoxia Through Akt/Mitogen-Activated Protein Kinase/Extracellular Signal
Regulated Kinase (Akt/MAPK/ERK) Pathway in Hypoxia-Ishchemic Encephalopathy.
AB - BACKGROUND Insulin growth factor 1 (IGF-1) is reported to modulate cell growth
and acts as potential therapy for traumatic brain injury. This study was designed
to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem
cells (NSCs). MATERIAL AND METHODS A hypoxia model was constructed using NSCs
separated from the hippocampus of rat. NSCs were divided into four groups: cells
under normoxic conditions that acted as controls (C group), cells under hypoxia
(H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia
with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the
IGF-1 receptor (HIP group). The cell viability and apoptosis were respectively
measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)
assay and flow cytometry. Finally, the phosphorylation levels of apoptosis
associated proteins and key kinases in the phosphatidylinositol-3-kinase
(PI3K)/AKT and the mitogen-activated protein kinase/extracellular signal
regulated kinase (MAPK/ERK) pathways were detected by Western blot analysis.
RESULTS In comparison with the H group, the cell viability was increased while
the cell apoptosis was reduced by IGF-1 in the HI group. Besides, the expression
levels of Bax, cytochrome c, and activated caspase-3 were all improved in the H
group, and the remarkable differences were eliminated in the HI group compared
with the C group. The expression level of Bcl-2 was the opposite. Additionally,
down-regulations of phosphorylated AKT, MAPK, and ERK induced by hypoxia were all
improved by IGF-1. All the influences of IGF-1 were weakened by addition of PPP.
CONCLUSIONS IGF-1 increased cell viability while decreasing apoptosis in hypoxic
NSCs through the PI3K/AKT and MAPK/ERK pathways.
PMID- 28420866
TI - Male New Zealand robins (Petroica longipes) cater to their mate's desire when
sharing food in the wild.
AB - In many species that have bi-parental care, food-sharing males provide vital
nutritional resources to their mates during reproduction. However, it is
currently unknown whether females can signal specific desires to their mates, or
if males can cater to female desire in the wild. Here we investigate whether and
how wild male North Island robins (Petroica longipes) respond to changes in their
mates' desires and nutritional need when sharing food. We demonstrate that wild
female robins' desire for particular foods changes over short time periods; when
given the choice between two types of insect larvae, females prefer the type they
have not recently eaten. In our experiments, wild male robins preferentially
shared the larvae type that their mate was most likely to desire and also
increased the quantity of food shared if she had begun incubating. Males catered
to their mates' desire when female behaviour was the only cue available to guide
their choices. This is the first evidence that females may behaviourally
communicate their specific food desires to their mates, enabling males to cater
to fine-scale changes in their mates' nutritional requirements in the wild. Such
a simple behaviour-reading mechanism has the potential to be widespread among
other food-sharing species.
PMID- 28420867
TI - Interaction effects of polyfluoroalkyl substances and sex steroid hormones on
asthma among children.
AB - To evaluate the interactions between polyfluoroalkyl substances (PFASs) and
reproductive hormones and associated asthma, a total of 231 asthmatic and 225 non
asthmatic adolescents were selected from northern Taiwan in the Genetic and
Biomarkers study for Childhood Asthma from 2009-2010. The interaction between
PFASs and reproductive hormones on asthma was analyzed with a two-level binary
logistic regression model. The results showed that, among asthmatics, PFASs were
positively associated with estradiol levels and negatively associated with
testosterone levels. However, only significant association was identified for
PFNA and estradiol in control group. After controlling for hormone levels,
associations between PFAS exposure and asthma were consistently stronger among
children with higher than lower estradiol, with odds ratios (OR) for asthma
ranging from 1.25 for PFOS (95% Confidence Interval [CI]: 0.90, 1.72) to 4.01 for
PFDA (95% CI: 1.46, 11.06) among boys and 1.25 for PFOS (95% CI: 0.84, 1.86) to
4.16 for PFNA (95% CI: 1.36, 12.73) among girls. Notably, the interactions
between estradiol and PFASs were significant for PFOS (p = 0.026) and PFNA (p =
0.043) among girls. However, testosterone significantly attenuated the
association between PFOS and asthma across sex. In conclusions, our findings
suggested that reproductive hormones amplify the association between PFASs and
asthma among adolescents.
PMID- 28420868
TI - Aurachin SS, a new antibiotic from Streptomyces sp. NA04227.
PMID- 28420869
TI - Verification of oligomycin A structure: synthesis and biological evaluation of 33
dehydrooligomycin A.
AB - Although, the structure of oligomycin A (1) was confirmed by spectroscopic and
chemical evaluations, some crystallographic data cast doubt on the originally
adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was
suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1
propenyl). To clarify this matter we synthesized and evaluated 33
dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O
mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin
(2) and results of quantum chemical calculations have shown that this derivative
exists in the keto rather than in the enol tautomer 2a. The in vitro
antimicrobial activity of 2 was approximately two times weaker in comparison with
oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp.
strains and similar activity against certain filamentous fungi. The docking
binding estimate of 2 with FOF1ATP synthase showed a slight decrease in binding
affinity for 2 when compared with oligomycin A; that correlated with its activity
against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in
vitro antiproliferative activities of 2 are also discussed.
PMID- 28420870
TI - Time-Resolved Visual Chiral Discrimination of Cysteine Using Unmodified CdTe
Quantum Dots.
AB - Herein, we demonstrate a simple yet novel luminescence assay for visual chiral
discrimination of cysteine. Thioglycolic acid (TGA)-capped cadmium-telluride
(CdTe) quantum dots (QDs) exposing green emission were directly synthesized in
aqueous solution. The interaction between cysteine molecules and CdTe QDs induced
the aggregation of QDs via hydrogen bonding. As a result of electronic coupling
within these aggregates, a redshift both in the absorption and emission spectra
of QDs occured. The difference in the kinetics of the interactions between L- and
D-cysteine with CdTe QDs led to chiral recognition of these enantiomers. Addition
of D-cysteine to CdTe QDs in a basic media caused a green-to-yellow color change,
while no color alteration in QDs emission was observed in the presence of L
cysteine after 2 hours. Notably, the QDs used in the proposed assay are free from
any labling/modification, which makes the present strategy highly attractive for
sensing applications. Furthermore, the presented chiral assay is able to
determine the enantiomeric excess (ee) of D-cysteine in the whole range of ee
values (from -100% to 100%).
PMID- 28420871
TI - Interactive Outlining of Pancreatic Cancer Liver Metastases in Ultrasound Images.
AB - Ultrasound (US) is the most commonly used liver imaging modality worldwide. Due
to its low cost, it is increasingly used in the follow-up of cancer patients with
metastases localized in the liver. In this contribution, we present the results
of an interactive segmentation approach for liver metastases in US acquisitions.
A (semi-) automatic segmentation is still very challenging because of the low
image quality and the low contrast between the metastasis and the surrounding
liver tissue. Thus, the state of the art in clinical practice is still manual
measurement and outlining of the metastases in the US images. We tackle the
problem by providing an interactive segmentation approach providing real-time
feedback of the segmentation results. The approach has been evaluated with
typical US acquisitions from the clinical routine, and the datasets consisted of
pancreatic cancer metastases. Even for difficult cases, satisfying segmentations
results could be achieved because of the interactive real-time behavior of the
approach. In total, 40 clinical images have been evaluated with our method by
comparing the results against manual ground truth segmentations. This evaluation
yielded to an average Dice Score of 85% and an average Hausdorff Distance of 13
pixels.
PMID- 28420872
TI - Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor
induced Angiogenesis via Downregulation of Osteopontin Expression.
AB - Angiogenesis plays a critical role in the progression and vulnerability of
atherosclerotic plaques; however, the orchestration of angiogenesis in
atherosclerotic plaque formation remains unclear. The results of microarray
analysis, real-time PCR and immunohistochemical analyses showed that
Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly
decreased, while that of osteopontin (OPN) was increased, in atherosclerotic
plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and
OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic
plaques. The results of an in vitro study showed that Hes-1 was downregulated,
while OPN was upregulated, in a time- and dose-dependent manner in human
umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1
knockdown was found to have transcriptional promotion effect on OPN expression in
HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary,
Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis
in vitro and in vivo. The results of this study suggest that decreased Hes-1
expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by
upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN
expression may be a promising strategy to prevent vulnerable plaque formation in
patients with atherosclerosis.
PMID- 28420873
TI - Viewing immune regulation as it happens: in vivo imaging for investigation of
regulatory T-cell function.
AB - Regulatory T cells (Tregs) play indispensable roles in the immune system, in
limiting excessive or inappropriate immune and inflammatory responses. They
achieve this function via effects on other immune cells in the secondary lymphoid
system, and in peripheral locations such as skin, gut and bone marrow. As for the
more extensively studied cellular players in the immune system, particularly
dendritic cells and conventional T cells, in vivo imaging of Tregs via two-photon
(or multiphoton) microscopy (MPM) has been central to the development of
understanding how these cells function. In this brief review, we will describe
the studies that have utilised MPM to examine Treg behaviour in vivo. These
studies have investigated Treg behaviour in lymph nodes and spleen, as well as in
peripheral organs such as skin, small intestine and bone marrow. The findings
from these experiments underline how assumptions made about Treg function based
on results of in vitro experiments are often not supported by direct
visualisation of these cells in their normal in vivo settings. Together this work
reveals that only via MPM analysis can Treg function be investigated in the
complicated multicellular environments where conventional T cells, antigen
presenting cells and other potential cellular targets of Tregs are present with
each undergoing their own specific actions.
PMID- 28420874
TI - Therapeutic targeting using tumor specific peptides inhibits long non-coding RNA
HOTAIR activity in ovarian and breast cancer.
AB - Long non-coding RNAs (lncRNAs) play key roles in human diseases, including
cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA)
provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but
targeting lncRNAs in vivo has proven to be difficult. In the current study, we
describe a peptide nucleic acids (PNA)-based approach to block the ability of
HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and
resensitize resistant ovarian tumors to platinum. Treatment of HOTAIR
overexpressing ovarian and breast cancer cell lines with PNAs decreased invasion
and increased chemotherapy sensitivity. Furthermore, the mechanism of action
correlated with reduced nuclear factor-kappaB (NF-kappaB) activation and
decreased expression of NF-kappaB target genes matrix metalloprotease 9 and
interleukin 6. To deliver the anti-lncRNA to the acidic (pH approximately 6)
tumor microenvironment, PNAs were conjugated to pH-low insertion peptide (pHLIP).
Treatment of mice harboring platinum-resistant ovarian tumor xenografts with
pHLIP-PNA constructs suppressed HOTAIR activity, reduced tumor formation and
improved survival. This first report on pHLIP-PNA lncRNA targeting solid tumors
in vivo suggests a novel cancer therapeutic approach.
PMID- 28420875
TI - Down-regulation of cholinergic signaling in the habenula induces anhedonia-like
behavior.
AB - Dysfunction of cholinergic signaling in the brain has long been believed to be
associated with depressive disorders. However, the functional impact of habenular
cholinergic signaling on the specified depressive behaviors is not well
understood. Here, we demonstrated that the expression levels of cholinergic
signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated
in a chronic restraint stress (CRS) rat model of depression, in which rats
display depression-like behaviors such as anhedonia and mood despair. Moreover,
knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like
behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed
by chronic administration of the selective serotonin reuptake inhibitor
fluoxetine. To determine whether habenular cholinergic signaling is associated
with regulation of dopamine neurons in the ventral tegmental area (VTA) and
serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic
mice expressing the Designer Receptors Exclusively Activated by Designer Drugs
(DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the
excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5
hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation
was recapitulated in the postmortem habenula of suicide victims diagnosed with
major depressive disorder (MDD).
PMID- 28420876
TI - Examining gray matter structure associated with academic performance in a large
sample of Chinese high school students.
AB - Achievement in school is crucial for students to be able to pursue successful
careers and lead happy lives in the future. Although many psychological
attributes have been found to be associated with academic performance, the neural
substrates of academic performance remain largely unknown. Here, we investigated
the relationship between brain structure and academic performance in a large
sample of high school students via structural magnetic resonance imaging (S-MRI)
using voxel-based morphometry (VBM) approach. The whole-brain regression analyses
showed that higher academic performance was related to greater regional gray
matter density (rGMD) of the left dorsolateral prefrontal cortex (DLPFC), which
is considered a neural center at the intersection of cognitive and non-cognitive
functions. Furthermore, mediation analyses suggested that general intelligence
partially mediated the impact of the left DLPFC density on academic performance.
These results persisted even after adjusting for the effect of family
socioeconomic status (SES). In short, our findings reveal a potential
neuroanatomical marker for academic performance and highlight the role of general
intelligence in explaining the relationship between brain structure and academic
performance.
PMID- 28420877
TI - Proximate effects of temperature versus evolved intrinsic constraints for
embryonic development times among temperate and tropical songbirds.
AB - The relative importance of intrinsic constraints imposed by evolved physiological
trade-offs versus the proximate effects of temperature for interspecific
variation in embryonic development time remains unclear. Understanding this
distinction is important because slow development due to evolved trade-offs can
yield phenotypic benefits, whereas slow development from low temperature can
yield costs. We experimentally increased embryonic temperature in free-living
tropical and north temperate songbird species to test these alternatives. Warmer
temperatures consistently shortened development time without costs to embryo mass
or metabolism. However, proximate effects of temperature played an increasingly
stronger role than intrinsic constraints for development time among species with
colder natural incubation temperatures. Long development times of tropical birds
have been thought to primarily reflect evolved physiological trade-offs that
facilitate their greater longevity. In contrast, our results indicate a much
stronger role of temperature in embryonic development time than currently
thought.
PMID- 28420879
TI - Evolutionary genetics: Fantastic beasts - cephalopod RNA recoding.
PMID- 28420880
TI - Balancing Speed and Coverage by Sequential Seeding in Complex Networks.
AB - Information spreading in complex networks is often modeled as diffusing
information with certain probability from nodes that possess it to their
neighbors that do not. Information cascades are triggered when the activation of
a set of initial nodes - seeds - results in diffusion to large number of nodes.
Here, several novel approaches for seed initiation that replace the commonly used
activation of all seeds at once with a sequence of initiation stages are
introduced. Sequential strategies at later stages avoid seeding highly ranked
nodes that are already activated by diffusion active between stages. The gain
arises when a saved seed is allocated to a node difficult to reach via diffusion.
Sequential seeding and a single stage approach are compared using various seed
ranking methods and diffusion parameters on real complex networks. The
experimental results indicate that, regardless of the seed ranking method used,
sequential seeding strategies deliver better coverage than single stage seeding
in about 90% of cases. Longer seeding sequences tend to activate more nodes but
they also extend the duration of diffusion. Various variants of sequential
seeding resolve the trade-off between the coverage and speed of diffusion
differently.
PMID- 28420878
TI - Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial
Treatments.
AB - Due to the emergence of multi-drug resistant strains, development of novel
antibiotics has become a critical issue. One promising approach is the use of
transition metals, since they exhibit rapid and significant toxicity, at low
concentrations, in prokaryotic cells. Nevertheless, one main drawback of
transition metals is their toxicity in eukaryotic cells. Here, we show that the
barriers to use them as therapeutic agents could be mitigated by combining them
with silver. We demonstrate that synergism of combinatorial treatments
(Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8
fold their antimicrobial effect, when compared to their individual effects,
against E. coli and B. subtilis. We find that most combinatorial treatments
exhibit synergistic antimicrobial effects at low/non-toxic concentrations to
human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show
that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub
inhibitory concentrations, demonstrating this to be a possible mechanism of the
synergistic behavior. Together, these results suggest that these combinatorial
treatments will play an important role in the future development of antimicrobial
agents and treatments against infections. In specific, the cytotoxicity
experiments show that the combinations have great potential in the treatment of
topical infections.
PMID- 28420881
TI - Reduced biological effect of e-cigarette aerosol compared to cigarette smoke
evaluated in vitro using normalized nicotine dose and RNA-seq-based
toxicogenomics.
AB - Electronic cigarettes (e-cigarettes) use has increased globally and could
potentially offer a lower risk alternative to cigarette smoking. Here, we
assessed the transcriptional response of a primary 3D airway model acutely
exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were
generated with standard intense smoking regimens with careful consideration for
dose by normalizing the exposures to nicotine. Two e-cigarette aerosol dilutions
were tested for equivalent and higher nicotine delivery compared to 3R4F. RNA was
extracted at 24 hrs and 48 hrs post exposure for RNA-seq. 873 and 205 RNAs were
differentially expressed for 3R4F smoke at 24 hrs and 48 hrs using a pFDR < 0.01
and a [fold change] > 2 threshold. 113 RNAs were differentially expressed at the
highest dose of e-cigarette aerosol using a looser threshold of pFDR < 0.05, 3
RNAs exceeded a fold change of 2. Geneset enrichment analysis revealed a clear
response from lung cancer, inflammation, and fibrosis associated genes after 3R4F
smoke exposure. Metabolic/biosynthetic processes, extracellular membrane,
apoptosis, and hypoxia were identified for e-cigarette exposures, albeit with a
lower confidence score. Based on equivalent or higher nicotine delivery, an acute
exposure to e-cigarette aerosol had a reduced impact on gene expression compared
to 3R4F smoke exposure in vitro.
PMID- 28420882
TI - The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness
of glioma initiating cells.
AB - Glioma initiating cells (GICs) are thought to contribute to therapeutic
resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in
adults. Although the stem-like properties of GICs, such as self-renewal and
tumorigenicity, are epigenetically regulated, the role of a major chromatin
remodeling complex in human, the SWI/SNF complex, remains unknown in these cells.
We here demonstrate that the SWI/SNF core complex, that is associated with a
unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays
essential roles in stemness maintenance in GICs. The serum-induced
differentiation of GICs downregulated the endogenous expression of DPF1 and
DPF3a, and the shRNA-mediated knockdown of each gene reduced both sphere-forming
ability and tumor-forming activity in a mouse xenograft model. Rescue experiments
revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have
previously reported that d4-family members can function as adaptor proteins
between the SWI/SNF complex and NF-kappaB dimers, this does not significantly
contribute to maintaining the stemness properties of GICs. Instead, these
proteins were found to link a corepressor complex containing the nuclear
receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our
results indicate that DPF1 and DPF3a are potential therapeutic targets for
glioblastoma.
PMID- 28420883
TI - Leukocidins: staphylococcal bi-component pore-forming toxins find their
receptors.
AB - Staphylococcus aureus is a major bacterial pathogen that causes disease
worldwide. The emergence of strains that are resistant to commonly used
antibiotics and the failure of vaccine development have resulted in a renewed
interest in the pathophysiology of this bacterium. Staphylococcal leukocidins are
a family of bi-component pore-forming toxins that are important virulence
factors. During the past five years, cellular receptors have been identified for
all of the bi-component leukocidins. The identification of the leukocidin
receptors explains the cellular tropism and species specificity that is exhibited
by these toxins, which has important biological consequences. In this Review, we
summarize the recent discoveries that have reignited interest in these toxins and
provide an outlook for future research.
PMID- 28420884
TI - A CRISPR toolbox to study virus-host interactions.
AB - Viruses depend on their hosts to complete their replication cycles; they exploit
cellular receptors for entry and hijack cellular functions to replicate their
genome, assemble progeny virions and spread. Recently, genome-scale CRISPR-Cas
screens have been used to identify host factors that are required for virus
replication, including the replication of clinically relevant viruses such as
Zika virus, West Nile virus, dengue virus and hepatitis C virus. In this Review,
we discuss the technical aspects of genome-scale knockout screens using CRISPR
Cas technology, and we compare these screens with alternative genetic screening
technologies. The relative ease of use and reproducibility of CRISPR-Cas make it
a powerful tool for probing virus-host interactions and for identifying new
antiviral targets.
PMID- 28420886
TI - Hypertension: Hypertension in pregnancy: a risk factor for the whole family?
PMID- 28420885
TI - Oxidative stress, protein damage and repair in bacteria.
AB - Oxidative damage can have a devastating effect on the structure and activity of
proteins, and may even lead to cell death. The sulfur-containing amino acids
cysteine and methionine are particularly susceptible to reactive oxygen species
(ROS) and reactive chlorine species (RCS), which can damage proteins. In this
Review, we discuss our current understanding of the reducing systems that enable
bacteria to repair oxidatively damaged cysteine and methionine residues in the
cytoplasm and in the bacterial cell envelope. We highlight the importance of
these repair systems in bacterial physiology and virulence, and we discuss
several examples of proteins that become activated by oxidation and help bacteria
to respond to oxidative stress.
PMID- 28420887
TI - Kidney cancer: Targeting metabolism in RCC.
PMID- 28420888
TI - Global gene expression profiling of healthy human brain and its application in
studying neurological disorders.
AB - Brain function is governed by precise regulation of gene expression across its
anatomically distinct structures; however, the expression patterns of genes
across hundreds of brain structures are not clearly understood. Here, we describe
a gene expression model, which is representative of the healthy human brain
transcriptome by using data from the Allen Brain Atlas. Our in-depth gene
expression profiling revealed that 84% of genes are expressed in at least one of
the 190 brain structures studied. Hierarchical clustering based on gene
expression profiles delineated brain regions into structurally tiered spatial
groups and we observed striking enrichment for region-specific processes.
Further, weighted co-expression network analysis identified 19 robust modules of
highly correlated genes enriched with functional associations for neurogenesis,
dopamine signaling, immune regulation and behavior. Also, structural distribution
maps of major neurotransmission systems in the brain were generated. Finally, we
developed a supervised classification model, which achieved 84% and 81%
accuracies for predicting autism- and Parkinson's-implicated genes, respectively,
using our expression model as a baseline. This study represents the first use of
global gene expression profiling from healthy human brain to develop a disease
gene prediction model and this generic methodology can be applied to study any
neurological disorder.
PMID- 28420889
TI - Evaluation of Urinary Stone Composition and Differentiation between Urinary
Stones and Phleboliths Using Single-source Dual-energy Computed Tomography.
AB - The aim of this study was to investigate the utility of single-source dual-energy
computed tomography (SS-DECT) composition analysis in characterizing different
types of urinary stones and differentiating them from phleboliths. This study
included 29 patients with urinary stones who were scheduled for surgery. All
patients were scanned, first using single-energy computed tomography acquisition
and then DECT acquisition on SS-DECT. Dual-energy data were archived to a
Gemstone spectral imaging (GSI) viewer (GE Healthcare, Milwaukee, WI, USA).
Hounsfield units (HU) and effective atomic numbers (Zeff) were estimated using
the GSI viewer. The results of dual-energy analysis were compared with the
biochemical constitution of the stones. The chemical analysis determined that the
stones included 32 calcium-based, 6 cystine and 1 struvite stone. Both HU and
Zeff values were helpful in differentiating calcium-based stones from cystine and
struvite stones and phleboliths. The Zeff values of phleboliths were
significantly higher than those for struvite and cystine stones, whereas it was
difficult to distinguish phleboliths from struvite and cystine stones using the
HU values. Composition analysis using SS-DECT is helpful for distinguishing
urinary stone types and discriminating phleboliths from urinary stones. Zeff
values may be more useful than HU values for differentiating urinary stones from
phleboliths.
PMID- 28420890
TI - Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus
Infection in the Upper Gastrointestinal Tract.
AB - We retrospectively analyzed the cases of 14 patients (9 women, 5 men, mean age:
51.6 years) with cytomegalovirus (CMV) involvement in the esophagus, stomach,
and/or duodenum diagnosed at a single center, to determine their endoscopic
features and clinical backgrounds. Thirteen patients (92.9%) had hematologic
disease; the other had rheumatoid arthritis. Of the former, 12 patients underwent
allogeneic hematopoietic stem cell transplantation, and 9 of these patients had
graft-versus-host disease (GVHD) before undergoing esophagogastroduodenoscopy
(EGD). All 14 patients had been taking one or more immunosuppressive agents
including cyclosporine (n=10), corticosteroids (n=9), mycophenolic acid (n=6),
tacrolimus (n=3), and methotrexate (n=1). Tests for CMV antigenemia were positive
in 11 patients (78.6%). EGD examinations revealed esophageal (n=3), gastric
(n=9), and duodenal involvement (n=6). Macroscopically, esophageal lesions by CMV
infection presented as redness (n=1), erosions (n=1), and ulcers (n=1). Gastric
lesions manifested as redness (n=7), erosions (n=3), exfoliated mucosa (n=2), and
verrucous erosions (n=1). Mucosal appearances in the duodenum varied: redness
(n=2), ulcers (n=2), multiple erosions (n=2), single erosion (n=1), edema (n=1).
CMV was detected even in the intact duodenal mucosa (n=1). In conclusion,
physicians must recall the relevance of CMV infection when any mucosal
alterations exist in the upper gastrointestinal tract of immunosuppressed
patients.
PMID- 28420892
TI - Adenomyomatosis Concomitant with Primary Gallbladder Carcinoma.
AB - Some clinicians have proposed a relationship between gallbladder (GB) cancer and
adenomyomatosis (ADM) of the gallbladder, although the latter condition is not
considered to have malignant potential. We retrospectively reviewed the surgical
pathology database of patients who underwent resection for ADM of the gallbladder
at our institution from March 2005 to May 2015. In total, 624 patients underwent
surgical resection of the gallbladder with Rokitansky-Aschoff sinuses. Of these
cases, 93 were pathologically diagnosed with ADM of the gallbladder, with 44
(47.3%) classified macroscopically as fundal-type ADM, 26 (28.0%) as segmental
type, and 23 (24.7%) as diffuse-type ADM. In 3 of the 93 (3.2%) resected
specimens, early-stage GB carcinoma was detected, although preoperative imaging
did not suggest a malignant neoplasm of the gallbladder in any of these patients.
GB cancer subsequently developed in the mucosa of the fundal compartment distal
to the annular stricture of the segmental-type ADM in 2 of these patients and
against the background of the fundal-type ADM in 1 patient. This study revealed
the difficulty of early diagnosis of primary GB cancer in the setting of
concurrent ADM, and clinicians should be aware of this frequent coexistence.
PMID- 28420891
TI - Diagnostic Value of Dual-time-point F-18 FDG PET/CT and Chest CT for the
Prediction of Thymic Epithelial Neoplasms.
AB - We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of
thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of
PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio
of the standardized uptake value of the tumor and that of the aortic arch (T/M
ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN
patients. We used a multivariate logistic regression (MLR) analysis to estimate
the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and
chest CT using receiver operating characteristic (ROC) analyses. The ROC curve
revealed that the appropriate cut-off T/M ratio value for the highest accuracy
was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The
statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy
and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The
MLR analysis indicated that mediastinal fat infiltration was a predictor of
carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed
scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and
mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic
accuracy.
PMID- 28420893
TI - Scoliosis in Patients with Severe Cerebral Palsy: Three Different Courses in
Adolescents.
AB - Patients with cerebral palsy (CP) frequently present with scoliosis; however, the
pattern of curve progression is difficult to predict. We aimed to clarify the
natural course of the progression of scoliosis and to identify scoliosis
predictors. This was a retrospective, single-center, observational study. Total
of 92 CP patients from Asahikawasou Ryouiku Iryou Center in Okayama, Japan were
retrospectively analyzed. Cobb angle, presence of hip dislocation and pelvic
obliquity, and Gross Motor Function Classification System (GMFCS) were
investigated. Severe CP was defined as GMFCS level IV or V. The mean observation
period was 10.7 years. Thirtyfour severe CP patients presented with scoliosis and
were divided into 3 groups based on their clinical courses: severe, moderate and
mild. The mean Cobb angles at the final follow-up were 129 degrees , 53 degrees ,
and 13 degrees in the severe, moderate, and mild groups, respectively. The
average progressions from 18 to 25 years were 2.7 degrees /year, 0.7 degrees
/year, and 0.1 degrees /year in the severe, moderate, and mild curve groups,
respectively. We observed the natural course of scoliosis and identified 3
courses based on the Cobb angle at 15 and 18 years of age. This method of
classification may help clinicians predict the patients' disease progression.
PMID- 28420894
TI - Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal
Cancer.
AB - Currently, chemoradiation is the most widely used nonsurgical treatment for
esophageal cancer. However, some patients, particularly the very elderly or those
with severe vital organ dysfunction, face difficulty with the chemotherapy
component. We therefore examined the outcome of radiation therapy (RT) alone for
patients with esophageal cancer at our facility. Between January 2005 and
December 2014, 84 patients underwent RT at our hospital, and 78 of these patients
received concomitant chemotherapy. The remaining 6 patients underwent RT alone;
these patients were considered to be high-risk and to have no lymph node
metastasis (stage I). Five of them received irradiation up to a curative dose: 4
showed a complete response (CR) and 1 showed a partial response (PR). Of the
patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient
underwent endoscopic submucosal dissection (ESD) as salvage therapy for local
recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer
patients can be treated radically with RT alone under certain conditions. In the
future, to broaden the indications for RT monotherapy to include some degree of
advanced cancers, a novel concurrent therapy should be identified.
PMID- 28420895
TI - The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and
Its Implication in Human Prostate Cancer Cell Growth Inhibition.
AB - The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key
molecule that promotes cancer progression. We previously developed an adenoviral
vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene
therapy. The therapeutic effects are based on suppressing the growth of cancer
cells, but, the underlying molecular mechanism has not been fully clarified. To
elucidate this mechanism, we investigated the effects of Ad-REIC on the
expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed
that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC
also suppressed the cell growth of LNCaP cells. Since other researchers have
demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c
Myc protein positively regulate the expression of CD147, we investigated the
correlation between the CD147 level and the activation of MAPK and c-Myc
expression. Unexpectedly, no positive correlation was observed between CD147 and
its possible regulators, suggesting that another signaling pathway was involved
in the downregulation of CD147. This is the first study to show the
downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the
therapeutic effects of Ad-REIC may be due to the downregulation of the cancer
progression factor, CD147.
PMID- 28420896
TI - Toe Pinch Force in Male Type 2 Diabetes Mellitus Patients.
AB - We compared the toe pinch force in men with and without type 2 diabetes mellitus
(T2DM). Sixty-eight male T2DM patients and 35 apparently healthy men matched for
age, sex, and body mass index (BMI) were enrolled in this cross-sectional study.
We compared the toe pinch force between the subjects with and without T2DM, and
we evaluated the effect of diabetic polyneuropathy on toe pinch force in the
patients. The toe pinch force of the T2DM patients was significantly lower than
that of the subjects without diabetes (3.12+/-1.22 kg vs. 4.40+/-1.19 kg,
p<0.001). Multiple regression analysis showed that T2DM was a determinant of
reduced toe pinch force. In addition, the toe pinch force of patients with
diabetic polyneuropathy was significantly lower than that of patients without
diabetic polyneuropathy (2.31+/-0.93 kg vs. 3.70+/-1.07 kg, p<0.001). Multiple
regression analysis showed that diabetic polyneuropathy was a determinant of the
toe pinch force in men with T2DM, even after adjusting for age, BMI, HbA1c, and
duration of diabetes. Reduced toe pinch force is a fundamental feature of motor
dysfunction in men with T2DM, and diabetic polyneuropathy might be associated
with toe pinch force in these patients.
PMID- 28420897
TI - In Vivo Analysis of Three-Dimensional Dynamic Scapular Dyskinesis in Scapular or
Clavicular Fractures.
AB - The three-dimensional (3D) kinematics of the scapula were analyzed in vivo in 10
patients with scapular and 10 patients with clavicular fracture. Both the injured
shoulder and normal contralateral shoulder were evaluated by computed tomography
in the neutral and fully elevated positions. 3D rotational and translational
movements of the scapula relative to the thorax during arm elevation were
analyzed. A computer simulation program was used to compare rotational
elevation/depression in the coronal plane, anterior/posterior tilting in the
sagittal plane and protraction/retraction in the axial plane between the normal
and affected sides. Anterior/ posterior translational movement along the X-axis,
upward/downward movement along the Y-axis, and lateral/ medial movement along the
Z-axis in the Euler space during forward elevation were also compared. In
scapular fracture, rotational elevation of the scapula decreased in the coronal
plane and posterior tilting of the scapula increased in the sagittal plane.
Anterior and superior translation were higher in scapular fracture than in the
corresponding normal sides. However, no significant abnormal rotational and
translational kinematic changes were observed during elevation in clavicular
fracture. In vivo 3D computerized motion analysis was useful for evaluating
scapular dyskinesis. Scapular fracture can cause scapular dyskinesis, but not all
clavicular fractures alter scapular motion biomechanics.
PMID- 28420898
TI - Comparison of Kidney Function between Gestational Hypertension and Preeclampsia.
AB - Although gestational hypertension (GH) is thought to be different from
preeclampsia (PE), in Japan GH and PE are usually treated as the same disease
(i.e., pregnancy-induced hypertension). Here we sought to determine whether there
are any differences in fetal growth and maternal kidney function between
pregnancies with PE and those with GH. We retrospectively analyzed 61 GH patients
and 60 PE patients with singleton pregnancies who delivered at Okayama University
Hospital (2008-2015). We compared maternal and perinatal outcomes and maternal
kidney function parameters between the GH and PE pregnancies. The mean values of
maternal age (p=0.01), gestational age at delivery (p<0.0001), placental weight
(p=0.002), birth weight and height (p<0.0001, p=0.0001), and head circumference
standard deviation score (p=0.007) of newborns of the GH group were significantly
higher than those of the PE group. The duration until termination of PE or GH was
not significantly correlated with kidney function. The birth weight percentile
was significantly correlated with kidney function in PE but not GH. However, GH
patients with poor kidney function and small-for-gestational age infants showed
perinatal outcomes similar to those of the PE group. Monitoring kidney function
is thus important for determining the severity of PE and GH.
PMID- 28420899
TI - Three-Dimensional Imaging of Lymphatic System in Lymphedema Legs Using
Interstitial Computed Tomography-lymphography.
AB - As a new trial, we used interstitial computed tomography-lymphography (CT-LG) in
10 patients with lower extremity lymphedema (n=20 limbs) at stage 0, 1, 2, or 3
under the International Society of Lymphology (ISL) classification. In all cases,
CT-LG, lymphoscintigraphy, and indocyanine green fluorescence-lymphography (ICG
LG) were performed. In the examination of the ascending level of depicted
lymphatic vessels, we measured the diameters of lymphatic vessels detected with
CT-LG and conducted an image analysis of dermal backflow of lymph (DB). CT-LG had
better resolution than lymphoscintigraphy and enabled the clear visualization of
lymphatic vessels with a minimum lumen size of 0.7 mm. CT-LG also showed the
three-dimensional architecture of the DB, which originated from deep lymphatic
collectors via branched small lymphatic vessels. Our findings are quite valuable
not only for detailed examinations of lymphedematous sites and for the lymphedema
surgery, but also for investigations of the pathogenesis of lymphedema which has
not yet been established. We observed that lymphoscintigraphy could show the
lymphatic vessels up to the thigh level in all cases, whereas CT-LG enabled the
vessels' visualization up to the leg level at maximum. In conclusion, CT-LG
provided adequate and detailed three-dimensional imaging of the lymphatic system
in lymphedema patients.
PMID- 28420900
TI - Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy.
AB - Newly published clinical practice guidelines recommend intracranial pressure
(ICP) monitoring in critical care for the management of pediatric acute
encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly
studied. We recently performed direct ICP monitoring for two patients. We
observed that although the direct ICP monitoring had clinical benefits with less
body weight gain and no vasopressor use in both cases, this monitoring technique
is still invasive. Future studies should determine the utility of non-invasive
ICP monitoring systems in pAE to further improve the quality of intensive-care
management.
PMID- 28420901
TI - Discrepancy between Non-invasive Prenatal Genetic Testing (NIPT) and Amniotic
Chromosomal Test due to Placental Mosaicism: A Case Report and Literature Review.
AB - We experienced a case of advanced maternal age in which a fetus was found to be
positive for trisomy 18 at re-examination following indeterminate non-invasive
prenatal genetic testing (NIPT), the amniotic fluid chromosomal test revealed a
normal karyotype, and confined placental mosaicism (CPM) was observed in an SNP
microarray analysis of the placenta. The child was born with no defects or
complications. In the present case, the result of the original NIPT at week 15 of
pregnancy was indeterminate and the subsequent re-examination result was
positive; since the definitive normal diagnosis was not reported until the latter
half of week 21, the pregnant patient was subjected to psychological stress for a
long period of time. The problem with NIPT is that most of the fetus-derived cell
free DNA in the maternal blood is not derived directly from the fetus but from
the villus cells of the placenta, leading to indefinite diagnoses; for that
reason, the pregnant patient was subjected to psychological stress for a long
period of time. Of the 18,251 cases undergoing NIPT in the past 2 years in Japan,
51 had indeterminate results; this was the second case in which a subsequent re
examination gave a positive result for trisomy 18.
PMID- 28420903
TI - Contemporary medical education in remote lands.
PMID- 28420902
TI - A Combination Therapy of Partial Nephrectomy and Cryoablation Achieved Good
Cancer Control and Renal Function in Bilateral Synchronous Renal Cell Carcinoma.
AB - We report the case of a 58-year-old Japanese man with bilateral synchronous renal
cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69
mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic
embolization was performed for the left tumor, and 1 month later, a right open
partial nephrectomy was performed. No recurrence was observed during a 16-month
follow-up, and the serum creatinine level has been stable. The prognosis of
bilateral synchronous RCC is better than that of dialysis patients. The novel
approach of combining cryoablation and partial nephrectomy can achieve good
cancer control and renal function in bilateral RCC.
PMID- 28420904
TI - Estimating risk of atherosclerotic cardiovascular diseases in non-atherosclerotic
Pakistani patients: Study conducted at National Institute of Cardiovascular
Diseases, Karachi, Pakistan.
AB - OBJECTIVE: To assess ten-year and lifetime estimated cardiovascular disease risks
in non-atherosclerotic subjects. METHODS: This cross-sectional study was carried
out at the National Institute of Cardiovascular Disease, Karachi, from July 2014
to March 2015, and comprised male and female subjects with multi-ethnic
background, aged 20-79 years and having non-atherosclerotic disease. SPSS 22 was
used for data analysis. RESULTS: Of the 437 participants, 174(39.8%) were men and
263(60.2%) were women. The overall mean age was 42.65+/-11.45 years. The mean age
of men was 43.3+/-12.1 years and that of women was 42.2+/-10.8 years. Moreover,
ten-year and lifetime risk assessment rates were higher in men (50[28.2%] and
86[49.4%] respectively) compared to women (28[10.6%] and 84[31.9%],
respectively). CONCLUSIONS: Urdu-speaking Pakistanis were found to be at higher
risk from atherosclerotic cardiovascular disease.
PMID- 28420905
TI - Effects of supervised aerobic training on the levels of anti-Mullerian hormone
and adiposity measures in women with normo-ovulatory and polycystic ovary
syndrome.
AB - OBJECTIVE: To evaluate the change in the levels of anti-Mullerian hormone,
adiponectin, weight loss and fertility parameters in obese women with or without
polycystic ovary syndrome, following 12 weeks of supervised aerobic exercise.
METHODS: This study was conducted from August 2013 to October 2014 among obese
women with or without polycystic ovary syndrome referred to Obstetrics and
Gynecology clinic, Mansoura University Hospital, Faculty of Medicine, Mansoura,
Egypt. Patients were classified into three age-matched groups; group A had
controls, group B had patients with polycystic ovary syndrome and group C had
obese women. Anti-Mullerian hormone, adiponectin, follicle-stimulating hormone,
oestrogen, fasting insulin, fasting glucose, homeostasis model of assessment of
insulin resistance, antral follicle count, hirsutism score, weight, menstrual
cyclicity and ovulatory function were assessed at baseline and following 12 weeks
of supervised aerobic exercise. Statistical analysis was performed using SPSS 17.
RESULTS: Of the 90 patients, there were 30(33.3%) in each group. The mean age was
28.7+/-3.84 years in group A, 27.9+/-4.1 years in group B and 27.6+/-5.7 in group
C. The 30(33.3%) participants who responded to aerobic exercise interventions
showed significant improvements in reproductive function), with lower baseline
anti-Mullerian hormone levels, greater weight loss and higher adiponectin level
compared to the the 30(33.3%) participants who did not respond to the exercise
programme. Weight loss, fertility hormones, follicle-stimulating hormone,
prolactin, oestrogen, antral follicle count, baseline anti-Mullerian hormone, and
adiponectin were significantly correlated to the improvement in reproductive
function (p<0.05 each). The change in anti-Mullerian hormone and adiponectin
levels correlated significantly with physical activity level in both responders
and non-responders (p<0.05). In women with anovulatory syndromes, there were
significant improvements in ovarian process with an ovulation rate of 13(43.3%)
and a restoration of menstrual cycle with a rate of 17(56.7 %) following 12 weeks
of supervised aerobic exercise. CONCLUSIONS: Moderate aerobic training for 12
weeks had a positive significant effect on reproductive functions via modulating
adiposity, the levels of adiponectin, anti-Mullerian hormone and fertility
hormones.
PMID- 28420906
TI - Comparison of ultrasound and ultrasound plus nerve stimulator guidance axillary
plexus block.
AB - OBJECTIVE: To evaluate the characteristics of axillary plexus blockade applied
using ultrasound only and using ultrasound together with nerve stimulator in
patients undergoing planned forearm, wrist or hand surgery. METHODS: This
randomised, prospective, double-blinded, single-centre study was conducted at
Ankara Numune Training and Research Hospital, Ankara, Turkey, from November 2014
to August 2015, and comprised patients undergoing forearm, wrist or hand surgery.
Participants were separated into 2 groups. In Group 1, the nerve roots required
for the surgical site were located one by one and local anaesthetic was applied
separately to each nerve for the block. In Group 2, the vascular nerve bundle was
located under ultrasound guidance and a total block was achieved by administering
all the local anaesthetic within the nerve sheath. In the operating room,
standard monitorisation was applied. Following preparation of the skin, the
axillary region nerve roots and branches and vascular structures were observed by
examination with a high-frequency ultrasound probe. In both groups, a 22-gauge,
5cm block needle was entered to the axillary region with visualisation of the
whole needle on ultrasound and 20ml local anaesthetic of 0.5% bupivacaine was
injected. SPSS 19 was used for data analysis. RESULTS: Of the 60 participants,
there were 30(50%) in each group. The mean age was 39.1+/-15 years in the group 1
which was the ultrasound nerve stimulation group, and 41.5+/-14.3 years in group
2. The duration of the procedure was longer in group I than in group 2 (p<0.05).
Patient satisfaction values during the procedure were higher in group 2(p<0.05).
In the ulnar sensory examination, the values of the patients in group 1were
higher at 10, 15, 20 and 25 minutes (p<0.05). In the median, radial and ulnar
motor examination, the values of the patients in group 1were higher at 15 and 20
minutes (p<0.05). CONCLUSIONS: Brachial plexus blockade via axillary approach
guided by ultrasound offered excellent quality of sensory and motor block
equivalent to that of the nerve stimulator-guided technique.
PMID- 28420907
TI - Effectiveness of health education programme: Level of knowledge about prevention
of cervical cancer among Saudi female healthcare students.
AB - OBJECTIVE: To evaluate the effectiveness of health education programme on the
knowledge of human papilloma virus among female medical students. METHODS: This
quasi-experimental study was conducted in 2014 at the Princess Nourah bint
Abulrahman University, Riyadh, Saudi Arabia, and comprised female medical
students. An intervention programme was implemented in the form of lectures,
videos, posters, etc. on human papillomavirus. SPSS 20 was used for data
analysis. RESULTS: There were 535 participants in the study. There mean age was
20.3+/-1.3 years. After the intervention, there was a significant increase in the
level of knowledge. Of all, 495(92%) students recognised avoidance of sexually
transmitted disease, vaccination and screening as effective preventive measures.
In comparison to pre-intervention results, significantly higher percentage of
students defined risk factors: sexually transmitted disease 392(73.3%) versus
329(61.8%), and human papillomavirus 293(54.8%) versus 151(28.4%). Knowledge
regarding sensitivity, 280(52.3%) after the campaign versus 160(30.1%)before, and
time to perform Pap smear,229(42.8%) versus 113(21.1%),increased significantly
(p<0.05). CONCLUSIONS: Health education programme was effective in improving the
level of knowledge on human papillomavirus.
PMID- 28420908
TI - Assessment of personality type and medical specialty choice among medical
students from Karachi; using Myers-Briggs Type Indicator (MBTI) tool.
AB - OBJECTIVE: To assess personality type of medical students and associate it with
their choice of medical specialty. METHODS: This cross-sectional study was
conducted in February 2014 at one public and one private medical university of
Karachi, and comprised medical students. A self- administered questionnaire based
on Myers-Briggs type indicator was used to collect data which was analysed using
SPSS 20. RESULTS: Of the 400 participants, there were 200(50%) each from public
and private universities. Of all, 201(50.3%) students were found to be
extroverted and 199(49.8%) were introverted personality types. Clinical fields
were the main preference of students after their medical degree as selected by
317(79.2%) students; of the, Extroverted-Sensing-Feeling-Perceptive was the most
common type identified in39(7.2%) students. Extroverted-Sensing-Feeling
Perceptive 11(2.8%), Extroverted-Sensing-Thinking-Judging 12(3%), Extroverted
Sensing-Feeling-Judging 5(1.3%), Introverted-Sensing-Feeling-Judging 6(1.5%),
Introverted-Sensing-Thinking-Perceptive 7(1.8%) had preference for surgery,
medicine, gynaecology, paediatrics and cardiology, respectively. CONCLUSIONS:
Personality had significant impact on specialty and career choice.
PMID- 28420909
TI - Lidocaine and tenoxicam effectiveness for pain relief during Pipelle: Non
randomised double-blind placebo-controlled trial.
AB - OBJECTIVE: To compare the effectiveness of intrauterine lidocaine infusion with
lidocaine and intravenous tenoxicam for decreasing the pain levels associated
with endometrial biopsy. METHODS: This double-blind, placebo-controlled trial was
conducted at Fatih Sultan Mehmet Training and Research Hospital, Istanbul,
Turkey, from May to November 2015, and comprised patients undergoing endometrial
biopsy with Pipelle. Intrauterine lidocaine infusion, paracervical block with
lidocaine, intravenous tenoxicam or 4ml intravenous normal saline administered
prior to biopsy. The main outcome measure was pain intensity immediately
afterwards and 30minutes after biopsy, determined by a visual analogue scale
score. Number Cruncher Statistical System 2007 was used for statistical analyses.
RESULTS: Of the 232 participants, intrauterine lidocaine infusion group had
59(25.4%) patients, 57(24.6%) were controls while paracervical block group and
intravenous tenoxicam group each had 58(25%) patients. Both visual analogue scale
0 and 30 scores of the control group were significantly higher than the other
three groups (p<0.05). Also, the scores of intravenous tenoxicam group were
significantly higher than both intrauterine lidocaine infusion and paracervical
block with lidocaine groups (p<0.05 each). CONCLUSIONS: Intravenous tenoxicam had
a significantly lower effect than intrauterine lidocaine infusion and
paracervical block with lidocaine during the early period after the procedure.
PMID- 28420910
TI - Awareness and attitudes towards organ donation among medical students at King
Abdulaziz University, Jeddah, Saudi Arabia.
AB - OBJECTIVE: To assess awareness and attitude of medical students about organ
donation. METHODS: This cross-sectional study was conducted in 2014 at King
Abdulaziz University, Jeddah, Saudi Arabia, and comprised medical students. The
participants were asked about their religious and other beliefs towards organ
donation, their reasons for not donating organs, and their personal opinions
about organ donation through a questionnaire. SPSS 21 was used for data analysis.
RESULTS: Of the 481 participants, 250(52%) were females, and 231(48%) were males.
The overall mean age was 21.36+/-1.63 years. Besides, 437(90.9%) students knew
what organ donation means, 433(90%) supported organ donation, and 90(18.7%) knew
someone who had donated an organ. Moreover, 245(50.9%) participants were willing
to donate their organ to their family alone, 198(41.2%) were willing to donate to
any deserving patient while 439(91.3%) rejected that religion precluded organ
donation, and 354(73.6%) did not know about the grafting of organs from a man to
a woman and vice versa. CONCLUSIONS: Awareness and attitude towards organ
donation were not up to the mark among the participants.
PMID- 28420911
TI - Comparison of foeto-maternal outcome in pregnant women with hepatitis E - A
review of 12 years.
AB - OBJECTIVE: To compare adverse maternal and foetal outcome in pregnant women with
hepatitis E immunoglobulin M reactive versus non-reactive. METHODS: This
retrospective study was conducted at the Aga Khan University Hospital, Karachi,
and comprised records of pregnant patients at any gestational age with clinical
and biochemical evidence of hepatitis E from January 2002 and December 2014. .
Maternal and perinatal outcome of the subjects were analysed. SPSS 20 was used
for data analysis. RESULTS: Out of the 200 subjects, 168(84 %) were hepatitis E
immunoglobulin M reactive and 32(16%) were non-reactive. The overall mean age was
26.7+/-4.5 years. Also, 12(7%) patients in the immunoglobulin M reactive group
were admitted to intensive care unit compared to no one from the non-reactive
group. Similarly fulminant hepatic failure was seen in 12(7.1%) patients in the
immunoglobulin M reactive group compared to no one in the other group. Post
partum haemorrhage was more frequent in the immunoglobulin M reactive group
compared to the non-reactive group. There were 5(3%) maternal deaths in the
reactive group compared to no death in the other group. Moreover, 34(20.2%)
neonates of the immunoglobulin M reactive group needed neonatal intensive care
unit admission compared to none in the non-reactive group. There were 4(2.4%)
neonatal deaths in the reactive group. CONCLUSIONS: Participants in the
immunoglobulin M reactive group had a higher percentage of adverse foeto-maternal
outcomes compared to the non-reactive group.
PMID- 28420912
TI - Effectiveness of plain X-ray in detection of fish and chicken bone foreign body
in upper aerodigestive tract.
AB - OBJECTIVE: To assess the use of plain film radiology in the detection of fish and
chicken bones in the upper aerodigestive tract. METHODS: This retrospective chart
review was conducted at the Aga Khan University Hospital, Karachi, and comprised
medical charts of patients who had undergone oesophagoscopy for removal of fish
and chicken bone from 1990 to 2015.SPSS 19 was used for data analysis. RESULTS:
Of the 24 patients, foreign body was detected on X-ray in 7(29.2%) and through
fibre optic laryngoscopy in 13(54.2%).All the patients underwent surgical
intervention for removal of the foreign body. Also, 19(79.2%) patients underwent
direct laryngoscopy and 5(16.7%) required oesophagoscopy. The sensitivity with X
ray was 15% and specificity was zero. The sensitivity of fibre optic laryngoscopy
in comparison to intra-operative findings was 65% and the specificity was 100%.
CONCLUSIONS: X-ray was not found to be an ideal modality to diagnose fish or
chicken bone impaction in the upper aerodigestive tract.
PMID- 28420913
TI - Increasing usage of rapid diagnostics for Dengue virus detection in Pakistan.
AB - OBJECTIVE: To evaluate the trends in usage of dengue virus diagnostics in
Pakistan. METHODS: This retrospective study was conducted at the Aga Khan
University Hospital, Karachi, and comprised data for specimens tested for dengue
virus from January 2012 to December 2015. Test for dengue virus ribonucleic acid
by reverse transcription polymerase chain reaction, dengue virus antigen by
immunochromatic assay and for human immunoglobulin M against dengue virus by
enzyme-linked immunosorbent assay were reviewed. SPSS 17 was used for data
analysis. RESULTS: Overall, 33,577 specimens tested for dengue virus. Of them,
11,995 (35.7%) were positive. among them, 1,039(8.66%) were reported in 2012;
5,791(48.28%) in 2013; 1,027(8.56%) in 2014; and 4,138(34.49%) in 2015. In 2012,
966(93%) of the positive samples were diagnosed by immunoglobulin M-based method
and 73(7%) by non-structural protein-1 antigen. In 2013, 4,401(76%) samples were
tested positive by immunoglobulin M, 1,332(23%) by antigen and 58(1%) by
polymerase chain reaction. The trend continued in 2014, but in 2015, 2,111(51%)
of all dengue positive tests were determined by antigen testing, 1,969(47.6%) by
immunoglobulin M and 58(1.4%) by polymerase chain reaction. CONCLUSIONS: There
was a shift in usage of direct virus identification for rapid diagnosis of dengue
virus compared with host immunoglobulin M testing.
PMID- 28420914
TI - Simulation training using cadaver sheep chest in pleuroscopy - A step towards
skills enhancement.
AB - OBJECTIVE: For assessing the use of if simulation training on animal cadavers as
a useful tool for training in pleuroscopy. METHODS: The email-based cross
sectional study was conducted in December 2014 at Shaikh Zayed Hospital, Federal
Postgraduate Medical Institute, Lahore, Pakistan, and comprised respiratory
physicians and trainees after their participation in a two-day hands-on training
course on pleuroscopy and pleural medical procedures. The responses were analysed
and the responses of physicians and trainees were compared. RESULTS: Of the 44
individuals who attended the course and were contacted through emails, 38(86.4%)
responded, including 20(52.6%) physicians and 18(47.3%) trainees. All the
38(100%) subjects uniformly accepted the utility of simulation training in
enhancing education, improving skill, and improving confidence by repeated
practice, and felt that the inclusion of animal models for learning fundamental
pleuroscopic procedures can help a lot in teaching. CONCLUSIONS: Animal cadavers
can be used as an effective teaching tool for pleuroscopy training.
PMID- 28420915
TI - Paternal malparenting and offspring personality disorders: Mediating effect of
early maladaptive schemas.
AB - OBJECTIVE: To examine the mediating role of maladaptive schemas between
permissive/authoritarian parenting by fathers and personality disorders,
including histrionic, antisocial, narcissistic and depressive attitudes among
adults. METHODS: This cross-sectional study was conducted at the University of
Sargodha, Sargodha, Pakistan, and comprised university students. Data was
collected by administering the parental authority questionnaire, the young schema
questionnaire and the personality diagnostic questionnaire. SPSS 23 was used for
data analysis. The study was completed in one year. It was started from June 2014
and ended in June 2015. RESULTS: Of the 200 participants who were handed the
questionnaires, 100(50%) returned it fully filled up. Of them, 87(87%) were women
and 13(13%) were men. All scales had greater than 0.70 alpha reliability
coefficients. The values of skewness for all scales ranged from 0.10 to
0.86.Permissive parenting style had positive correlation with histrionic
(p<0.05), narcissistic (p<0.05) and antisocial personality disorders (p<0.01).
Authoritarian parenting had positive correlation with early maladaptive schemas
(p<0.01) and depressive personality disorder (p<0.05). CONCLUSIONS: Both
permissive and authoritarian parenting styles led to personality disorders among
offspring in the adult phase of their lives.
PMID- 28420916
TI - The effect of bariatric anaesthesia on postoperative pulmonary functions.
AB - OBJECTIVE: To evaluate respiratory function in the post-operative early period of
patients undergoing bariatric surgery using the sleeve gastrectomy technique.
METHODS: This prospective, observational study was conducted at Bulent Ecevit
University Health Application and Research Centre, Zonguldak, Turkey from June to
December 2014, and comprised patients with planned bariatric sleeve gastrectomy
under general anaesthesia. Participants were visited 12-24 hours before the
operation to record accompanying diseases and demographic data. Before the
operations, respiratory function test, maximum expiratory pressure, maximum
inspiratory pressure and arterial blood gas assessment tests were done and
recorded as T0. After one hour of the operation, Aldrete scores >9 and the above
mentioned tests were repeated and recorded as T1. SPSS 18 and MedCalc 12.2.1.0
were used for statistical analysis. RESULTS: Of the 76 participants, 60(78%) were
women and 16(21%) were men. The overall median age was 39 years (inter-quartile
range: 32-47 years). The mean and median values for forced expiratory volume in 1
second, forced vital capacity, maximum inspiratory pressure, maximum expiratory
pressure and the ratio between partial pressure of oxygen in arterial blood and
fraction of inspired oxygen at T0 were 101+/-17, 102+/-17, 66 (interquartile
range: 59-74), 114 (interquartile range: 100-138) and 379+/-49, respectively,
compared with 78+/-18, 76+/-18, 53 (interquartile range: 48-59), 85
(interquartile range: 73-95) and 331+/-49at T1 (p<0.001 each). Also, 38(50%)
participants were given sugammadex and 38(50%) were given neostigmine. At the end
of the test, sugammadex (odds ratio: 5.80; 95% confidence interval: 1.26-26.69;
p=0.024) and pre-operative ratio between partial pressure of oxygen in arterial
blood and fraction of inspired oxygen (odds ratio: 1.04, 95% confidence interval:
1.02-1.06; p<0.0001) were found to correlate significantly. CONCLUSIONS:
Impairment of respiratory function was found during the early post-operative
period.
PMID- 28420917
TI - Coping strategies, mental health and HIV status: Predictors of suicidal behaviour
among PWIDs.
AB - OBJECTIVE: To understand suicidal behaviour among people who inject drugs.
METHODS: This correlational, cross-sectional study was conducted in two Pakistani
cities of Gujrat and Jhelum from October 2015 to March 2016, and comprised male
injecting-drug users aged18-60 years. Multistage systematic random sampling
method was used. Urdu-translated versions of the brief cope inventory, mental
health status scale and suicidal behaviour questionnaire (revised) were
administered. SPSS 16 was used for data analysis. RESULTS: Of the 200
participants, 83(41.5%) were aged 26-32 years. The prevalence of human
immunodeficiency virus was in 94(47%) cases. Suicidal behaviour was positively
associated with psychological distress and human immunodeficiency virus status
(p<0.05), whereas it was negatively associated with mental health, psychological
well-being and coping strategies (p<0.05). Regression analysis showed mental
health index and psychological well-being were negative predictors, whereas
psychological distress and human immunodeficiency virus status were positive
predictors of suicidal behaviour among the participants (p<0.05). CONCLUSIONS:
The level of stress led people who inject drugs towards suicidal behaviour.
However, the level of stress varied according to the severity of human
immunodeficiency virus and poor mental health.
PMID- 28420918
TI - The role of psychological eating styles in obesity among Turkish adolescents: A
cross-sectional study.
AB - OBJECTIVE: To determine the relationship between eating behaviours and adiposity
indicators including body mass index, waist-hip ratio and waist-height ratio in
adolescents. METHODS: This descriptive, cross-sectional study was conducted at
Kirklareli University Health College, Kirklareli, Turkey, from April to June
2014, and comprised students of the 2013-14 academic year. Height and weight were
measured and students' body mass indexes were calculated. Waist and hip
circumferences were measured. Eating behaviours were evaluated using the three
factor eating questionnaire. SPSS 15 was used for data analysis. RESULTS: Of
the520, 353(67.9%) were female and 167(32.1%) were male. Cognitive restraint and
emotional eating scores of females were significantly higher than those of males
(p<0.05). Cognitive restraint scores of participants who were thin according to
the body mass index were significantly lower than participants who were at normal
weight and who were overweight (p<0.05). Body mass index was significantly and
positively correlated to cognitive restraint and emotional eating subscales,
whereas there was a significant negative correlation between emotional eating and
waist-height ratio (p<0.05 each). Cognitive restraint regarding food intake and
tendency to emotional eating increased the risk of obesity (p<0.05). CONCLUSIONS:
Being inclined to emotional eating and limiting food intake cognitively increased
the risk of obesity.
PMID- 28420919
TI - Association of arginine vasopressin receptor 1a gene polymorphisms with
hepatorenal syndrome.
AB - OBJECTIVE: To assess the association of arginine vasopressin receptor 1a gene
single nucleotide polymorphisms with type I hepatorenal syndrome. METHODS: The
case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou,
China, from January 2012 to June 2014, and comprised patients with type I
hepatorenal syndrome and individuals with cirrhosis who acted as the control
group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide
polymorphisms were analysed by high-resolution melting methods. Statistical
analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%)
were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age
was 42.21+/-11.30years in the hepatorenal syndrome group and 43.69+/-12.60in the
control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity
levels were 154.76+/-51.58, 49.30+/-24.67 and 33.42+/-3.69 in the hepatorenal
syndrome group compared to 181.26+/-64.46, 41.78+/-17.52 and32.98+/-4.81among
controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were
found in the distributions of arginine vasopressin receptor 1a gene rs113481894
locus T allele between type I hepatorenal syndrome patients and the control group
(odds ratio= 2.230; p= 0.040). CONCLUSIONS: T allele located at arginine
vasopressin receptor 1a receptor promoter rs113481894 locus may be associated
with the pathogenesis of type I hepatorenal syndrome.
PMID- 28420920
TI - The many guises of primary hyperparathyroidism: An unchanged scenario.
AB - OBJECTIVE: To study the causes, characteristics and outcome of treatment of
patients with primary hyperparathyroidism. METHODS: This retrospective cohort
analysis was conducted at the Jinnah Postgraduate Medical Centre, Karachi, and
comprised data of patients with primary hyperparathyroidism between 2004 and
2014. .SPSS 17 was used for data analysis. RESULTS: Of the 25 patients,1(4%)was
male and 24(96%) were female. The overall mean age was 41.72+/-15.9 years, with a
mean duration of symptoms of 4.1+/-3.3 years. The mean pre-operative parathyroid
hormone level was 879.48+/-793.51 pg/ml. Skeletal manifestations were reported in
17(68%) patients, whereas 4(16%) patients had renal stone disease. Besides,
2(8.0%) patients presented with severe abdominal pain, 1(4%) had asymptomatic
hypercalcaemia and 1(4%) patient presented with headache and was diagnosed as
parathyroid adenoma in the context of multiple endocrine neoplasia type 2A. All
patients underwent parathyroidectomy. A solitary adenoma was reported in 23(92%)
patients, carcinoma in 1(4%) and an adenoma with hyperplasia of other glands in
1(4%) patient. CONCLUSIONS: A high index of suspicion is required for early
diagnosis of primary hyperparathyroidism.
PMID- 28420921
TI - Potential of ascorbic acid as antioxidant on chemotherapeutic agent induced
change in morphology of testes.
AB - OBJECTIVE: To demonstrate the morphological changes in number of seminiferous
tubules that are produced by anthracycline doxorubicin on the testes of mice.
METHODS: This experimental study was conducted at Dow University of Health
Sciences, Karachi, from March to August 2012, and comprised male mice aged up to
five weeks. The mice were separated into 3 equal groups: A, B and C. Each animal
was treated with normal saline 1ml intraperitoneal in group A, doxorubicin alone
in group B and doxorubicin + vitamin C in group C. At the end of the study,
animals were sacrificed and the testes were kept in Bouin's fluid and tissue
processing and staining were done. SPSS 16 was used for data analysis. RESULTS:
Of the 30 mice, there were 10(33.3%) in each group. The overall mean age was 5+/
1 weeks. The mean number of tubules was 20.28+/-3.29 in group A, 9.39+/-3.01 in
group B and 18.56+/-2.82 in group C. The mean diameter of seminiferous tubules of
testes was 218.26 +/- 7.45um in group A, 123.96+/-11.84 in group B and 180.86+/
12.13 in group C (p<0.001). Co-administration of vitamin C with doxorubicin
significantly reduced (p<0.001) the seminiferous epithelial damage compared to
doxorubicin group. CONCLUSIONS: The antioxidant vitamin C had a significant role
in ameliorating the damage of testes induced by doxorubicin.
PMID- 28420922
TI - Relationship of anthropometric measures with bone mineral density in
postmenopausal non-osteoporotic, osteopenic and osteoporotic women.
AB - Background and objectives: Body mass index (BMI) has been shown to be a more
important predictor of bone mineral density (BMD). The objective of this study
was to investigate the relationship of anthropometric measures including body
mass index with bone mineral density in postmenopausal non-osteoporotic,
osteopenic and osteoporotic women. METHODS: In this cross sectional study
postmenopausal females between 50-70 years of age were recruited and divided into
three groups: non-osteoporotic (n=52), osteopenic (n=69) and osteoporotic females
(n=47). Anthropometric measures and bone mineral density were assessed. ANOVA was
applied to compare groups while Post hoc Tuckey's test was used for multiple
comparisons between the groups. Spearman's rho correlation was used to establish
correlations. RESULTS: Body mass index (p = 0.034) and hip circumference (p =
0.013) were significantly higher in osteopenic as compared to osteoporotic
females and waist to hip ratio was significantly higher (p = 0.005) in
osteoporotic as compared to non-osteoporotic females. Significant positive
correlation of body mass index was found with T-score (p = 0.022) and ultrasound
bone profile index (p< 0.001) in postmenopausal females. CONCLUSIONS: High body
mass index is associated with high bone mineral density and reduced fracture risk
in postmenopausal females. Increasing age and high waist to hip ratio can also
lead to reduced bone mineral density in postmenopausal females.
PMID- 28420923
TI - Effect of body mass index on early outcomes of coronary artery bypass grafting.
AB - OBJECTIVE: To assess the impact of body mass index on early outcomes of coronary
artery bypass grafting in terms of morbidity and mortality. METHODS: This
retrospective comparative study was conducted at Chaudhry Pervaiz Elahi Institute
of Cardiology, Multan, Pakistan, and comprised data of patients who underwent
isolated coronary artery bypass grafting from December 2007 to December 2015.
Analysis of variance and chi-square test were used for analysis of groups formed
on the basis of body mass index. SPSS 20 was used for data analysis. RESULTS: Of
the 2,366 patients, 830(35.1%) had normal body mass index, 1,024(43.3%) were
overweight, 402(16.9%)were obese and 110(4.6%) were morbidly obese. The overall
mean age was 55.82+/-9.58 years. The mean age of morbidly obese patients was
significantly lower (p=0.02). Additive euro score was high in patients with
normal body mass index (p=0.006). Post-op creatine kinase muscle and brain MB
levels and incidence of peri-operative myocardial infarction was significantly
high in obese and morbidly obese groups (p=0.002 and p=0.01, respectively).
Hospital stay time was significantly longer in obese and morbidly obese patients
(p=0.01). The incidence of post-operative complications was the same in all
groups (p>0.05). Operative mortality was also the same between the groups
(p=0.58). CONCLUSIONS: Higher body mass index was associated with increased risk
of short-term morbidity in terms of myocardial infarction after surgery and
increased length of hospital stay. Our study did not support the concept of
obesity paradox.
PMID- 28420924
TI - Physicians' and nurses' medical errors associated with communication failures.
AB - OBJECTIVE: To determine medical errors associated with communication failures
among physicians and nurses. METHODS: This cross-sectional, descriptive study was
conducted at 20 state hospitals and 14 training and research hospitals affiliated
with the Istanbul City Health Directorate in Turkey, and comprised physicians and
nurses. Data were collected between August 2012 and February 2013. A 16-item
questionnaire was used that included questions regarding socio-demographic
features such as age, gender, educational status, institution, occupation and
working years. Questions also aimed at determining medical errors related to
communication failures. The questionnaire was completed by the participants
during face-to-face interviews. RESULTS: Of the 2,273 participants, 1,654(72.8%)
were nurses and 619(27.2%) were physicians. Besides, 340(54.9%) physicians and
811(49.03%) nurses worked in state hospitals. The mean age of the physicians was
37.76+/-9.20 years (range: 22-62 years), and that of the nurses was 32.61+/-7.38
years (range: 17-62 years). Moreover, 137(22.1%) physicians and 258(15.3%) nurses
had previously experienced medical errors. Also, 74(54%) physicians and
135(52.3%) nurses had experienced medical errors due to some communication error.
The most common medical errors by physicians were incorrect drug administration
45(32.8%), and delivery of drugs to the wrong patient by nurses 103(40.7%). In
addition, 58(42.3%) physicians made medical errors in adult surgical clinic
services while 102(39.5%) nurses made medical errors in adult internal medicine
clinics. CONCLUSIONS: The majority of medical errors originated from
communication failures.
PMID- 28420925
TI - Effect of smoking on hearing loss in refractory's factory male worker with
occupational noise exposure in Iran.
AB - OBJECTIVE: To assess the effect of smoking on hearing loss in factory workers
with occupational noise exposure. METHODS: This cross-sectional study was
conducted at Birjand University of Medical Sciences, Birjand, Iran, from May to
July 2013, and comprised smoking and non-smoking factory male workers. All of
them were exposed to occupational noise level more than 85 decibels for at least
10 years. All participants underwent audiometric testing. SPSS 15 was used for
data analysis.. RESULTS: Of the 150 participants, 55(36.7%) were smokers and
95(63.3%) were non-smokers. The mean age of the participants was 43.26+/-7.81
years while the mean working experience was 15.51+/-3.87 years. Furthermore,
18(32.7%) of the smokers and 8(8.4%) of the non-smokers suffered tinnitus
(p=0.07). The mean noise intensity in the working place of the individuals was
89+/-2.63 A-weighted decibels. At a frequency of 500 Hz, the mean hearing loss
was 4.8+/-5.7 decibels among smokers and 3.3+/-4.6 decibels among non-smokers in
the left ear (p=0.52), whereas it was 4.8+/-5.1 decibels and 3.00+/-4.5 decibels
in the right ear (p=0.15). The difference between the smokers and the non-smokers
was significant in both ears at 1000Hz, 2000Hz, 4000Hz and 8000Hz (p<0.05 each).
CONCLUSIONS: Smoking had an additive role in hearing loss among workers who were
in close contact with excessive noise exposure.
PMID- 28420926
TI - Femto-lasik: The recent innovation in laser assisted refractive surgery.
AB - Femtosecond laser has been introduced in refractive surgery to create a thin
hinged corneal flap without using any blade. The current review was planned to
analyse and compare femtosecond-assisted laser in-situ keratomileusis (LASIK),
the latest refractive procedure, with conventional techniques in refractive
surgery. The analysis showed that femtosecond-assisted LASIK yielded more
predictable corneal flaps, lesser ocular aberrations, better uncorrected visual
acuity, lesser variations in intraocular pressure (IOP) and fewer chances of
developing dry eyes. Transient light sensitivity, diffuse lamellar keratitis,
opaque bubble layer, corneal haze and rainbow glare are some of the demerits of
femtosecond-assisted LASIK, but these can be prevented with certain precautions.
The early visual rehabilitation and preservation of corneal anatomy are added
benefits in the long run. Though it is expensive currently, the competition in
market is expected to cut down the cost soon.
PMID- 28420927
TI - In silico analysis of fragile histidine triad involved in regression of
carcinoma.
AB - Hepatocellular carcinoma (HCCa) is a primary malignancy of the liver. Many
different proteins are involved in HCCa including insulin growth factor (IGF) II
, signal transducers and activators of transcription (STAT) 3, STAT4, mothers
against decapentaplegic homolog 4 (SMAD 4), fragile histidine triad (FHIT) and
selective internal radiation therapy (SIRT) etc. The present study is based on
the bioinformatics analysis of FHIT protein in order to understand the proteomics
aspect and improvement of the diagnosis of the disease based on the protein.
Different information related to protein were gathered from different databases,
including National Centre for Biotechnology Information (NCBI) Gene, Protein and
Online Mendelian Inheritance in Man (OMIM) databases, Uniprot database, String
database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Moreover,
the structure of the protein and evaluation of the quality of the structure were
included from Easy modeler programme. Hence, this analysis not only helped to
gather information related to the protein at one place, but also analysed the
structure and quality of the protein to conclude that the protein has a role in
carcinoma.
PMID- 28420928
TI - Road traffic crash related injured and fatal victims in Karachi from 2007 to
2014: A time-series analysis.
AB - Injuries and deaths due to road traffic crashes (RTC) are major public health
concern. The Road Traffic Injury Research and Prevention Center, collects RTC
data on injuries and fatalities from five emergency departments in Karachi. Data
generating process (DGP) for RTC from 2007 to 2014, for monthly number of fatal
and injured victims were analyzed using autoregressive integrated moving average
and vector auto regression, time series models. Results provide strong evidence
that the DGP for the current levels of the number of fatalities and injured owing
to RTCs are significantly influenced by the own past history of the two series.
The analysis with the impulse-response function also indicated that there is a
slight seasonality pattern in the number of injured and fatalities. The similar
behaviour and association of the two variables suggest that certain conditions
e.g. road conditions, weather, volume of vehicles, and accidents might be
persistent in time in Karachi.
PMID- 28420929
TI - Perception of pathology as a future career choice among medical Students from
Karachi, Pakistan: Experience from a private medical school.
AB - To determine the perception of pathology as a future career choice among medical
students of a private medical school from Karachi, Pakistan. A descriptive cross
sectional study was conducted at the Aga Khan University, Karachi, Pakistan. A
total of 201 students participated in this study. All Students were approached
randomly to participate. A total of 201 students participant survey forms were
evaluated in this study. The overall satisfaction level with pathology was
observed in 61.8% of the students. Majority of the students understood
subspecialties which were a part of clinical medicine. Over half of the students
thought pathology as a specialty should be highlighted in a more integrated
manner (59.2%) with a minority favouring a separate pathology rotation (11.9%).
In conclusion, this study indicates that majority of students have a positive
approach towards the field of pathology and favour incorporating it in an
integrative way into the medical school curriculum.
PMID- 28420930
TI - Enterobius vermicularis in tubo-ovarian abscess: A rare and interesting
incidental finding - A case Report.
AB - Enterobius vermicularis is a common intestinal nematode; however, rare
extraintestinal Enterobius infections have been reported from different parts of
the world. Here, we present a case of tubo-ovarian abscess in an otherwise
healthy young sexually active female with no known comorbids with history of on
and off lower abdominal pain for one year and high grade fever for one month. On
the basis of further workup and radiological evaluation, a preoperative diagnosis
of right sided tubo-ovarian abscess was made and salpingo-oophorectomy was
performed laproscopically in July 2015. Histopathology of the resected tissue
revealed necrosis and in one area Enterobius vermicularis was identified
surrounded by neutrophils and eosinophil rich abscess. A final diagnosis of
severe acute and chronic salpingo-oophoritis with abscess formation, secondary to
Enterobius vermicularis was made. Signs and symptoms of parasitic involvement in
tubo-ovarian abscesses are not much different than usual presentations of pelvic
inflammatory diseases and identification of a parasite in a tubo-ovarian tissue
sample is a rare clinical finding. A high index of suspicion on the part of
histopathologist as well as clinician is important for timely diagnosis and
effective management of such cases.
PMID- 28420931
TI - Paediatrics primary myelofibrosis and acute stroke: A rare presentation.
AB - Idiopathic Myelofibrosis is a rare myeloproliferative disorder. In children, it
becomes even rarer. Herein, we report a case of idiopathic myelofibrosis of a 6
year old male patient who presented with complaints of pallor, petechiae and
bleeding from gums. Bone marrow aspirate showed afragmented haemodiluted smears
with erythroid and myeloid precursors scattered throughout. Trephine biopsy
showed increased background fibrotic activity along with clusters of histiocytes.
A diagnosis of paediatric primary myelofibrosis was made on biopsy. The patient
also developed a stroke that resulted in left-sided hemiparesis. An MRI suggested
an intraparenchymal haemorrhage along with meningeal extramedullary
haematopoiesis.
PMID- 28420932
TI - Sporadic actinomycosis of the hip complicated by Central Nervous System
infection.
AB - Actinomycosis is caused by the Gram positive filamentous Actinomyces bacterial
species that are normal commensals of the oral cavity. Due to their low
virulence, disease is rare in the immune competent patient. Although it may
afflict any system in the body, involvement of the musculoskeletal system is
uncommon. Here in, we describe the case of a 60 year old lady presenting with low
grade fever, left hip pain and drowsiness. She was diagnosed as left hip
actinomycosis on Computed tomogram (CT) guided biopsy and histopathological
analysis of infiltrative lesions identified on Magnetic Resonance Imaging (MRI).
She also had meningitis diagnosed on cerebrospinal fluid analysis which improved
with treatment of actinomycosis. Actinomycosis of the hip is rare, and occurs in
the presence of described predisposing factors. To the best of our knowledge,
this is the first case of sporadic actinomycosis of the hip complicated by
meningitis in an immune competent individual.
PMID- 28420933
TI - Gestational diabetes mellitus: Berlin and beyond.
AB - The Berlin Declaration is a landmark call to action, which encourages policy
makers to take early action to halt the type 2 diabetes epidemic. It emphasizes
the need for prevention, early detection, early control, and early access to the
right interventions. We believe these four pillars of early action in type 2
diabetes are as relevant to gestational diabetes mellitus (GDM) and action in the
latter will impact on the former. Therefore this statement, authored by 21
experts from 14 countries calls for early action in GDM. We highlight the
relative invisibility of GDM, and underscore the significance of GDM prevention
and management in the fight against diabetes. We also provide evidence for the
feasibility in applying each Berlin Declaration pillar to GDM, and highlight the
trans generational benefits this will have in containing the diabetes epidemic.
PMID- 28420934
TI - Preconception management of thyroid disorders.
AB - Thyroid function is closely interlinked with pregnancy. Maternal and foetal
outcomes can be improved if optimal thyroid function is achieved, and maintained
prior to conception. This needs a systematic approach which includes rational
screening, appropriate management, and pragmatic counseling. This review
describes pre-conception management of thyroid disorders, and completes an
earlier article on preconception management of other endocrine diseases.
PMID- 28420935
TI - Prevention of hypoglycaemia, the ASAP (Anticipate, Suspect, Act, Prevent)
strategy.
AB - This article describes a simple framework to prevent hypoglycaemia. Four
strategies of prevention are detailed, which correspond to four levels of
prevention (primordial, primary, secondary and tertiary). This framework, given
the mnemonic ASAP (As Soon As Possible) includes action to Anticipate and Avoid,
and Suspect and Screen hypoglycaemia. It also enjoins us to Act and Assist
persons with hypoglycaemia in a timely manner, while working to Prevent and
Protect them by using safer glucose lowering drugs and insulins.
PMID- 28420936
TI - LINX Reflux Management System - Is it a permanent solution for GERD?
PMID- 28420937
TI - Rise and stalling of public health in Pakistan.
PMID- 28420938
TI - Assessment of the 3-D vision syndrome among the Spectators of Three-Dimensional
(3-d) Movies in Karachi-Pakistan.
PMID- 28420939
TI - Oncolytic viral therapy.
PMID- 28420940
TI - PREVALENCE OF HEPATITIS B SURFACE ANTIGEN AND ANTIBODY IN HEALTHY SUBJECTS AND
PATIENTS WITH LIVER DISEASE.
PMID- 28420941
TI - Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory
Bowel Disease.
AB - Cytokines play an important role in the immunopathogenesis of inflammatory bowel
disease (IBD), including Crohn's disease and ulcerative colitis, where they drive
and regulate multiple aspects of intestinal inflammation. The imbalance between
proinflammatory and anti-inflammatory cytokines that occurs in IBD results in
disease progression and tissue damage and limits the resolution of inflammation.
Targeting cytokines have been novel strategies in the treatment of IBD. Recent
studies show the beneficial effects of anticytokine treatments to IBD patients,
and multiple novel cytokines are found to be involved in the pathogenesis of IBD.
In this review, we will discuss the recent advances of novel biologics in clinics
and clinical trials, and novel proinflammatory and anti-inflammatory cytokines
found in IBD with focusing on IL-12 family and IL-1 family members as well as
their relevance to the potential therapy of IBD.
PMID- 28420942
TI - Temporomandibular Disorders and Headache: A Retrospective Analysis of 1198
Patients.
AB - Aim. Headache is one of the most common diseases associated with
Temporomandibular Disorders (TMDs). The aim of this study was to evaluate,
retrospectively, if headache influences TMD's symptoms. Material and Methods. A
total sample of 1198 consecutive TMD patients was selected. After a neurological
examination, a diagnosis of headache, according to the latest edition of the
International Classification of Headache Disorders, was performed in 625
subjects. Patients were divided into two groups based on presence/absence of
headache: Group with Headache (GwH) and Group without Headache (GwoH).
Descriptive statistics and Chi-square index were performed. Results.
Sociodemographic (gender, marital status, and occupation) and functional factors,
occlusion (occlusal and skeletal classes, dental formula, and occlusal
abnormalities), and familiar pain did not show a statistically significant
correlation in either group. Intensity and frequency of neck pain, arthralgia of
TMJ, and myalgia showed higher correlation values in GwH. Conclusion. This study
is consistent with previous literature in showing a close relationship between
headache and TMD. All data underlines that headache makes pain parameters more
intense and frequent. Therefore, an early and multidisciplinary treatment of TMDs
should be performed in order to avoid the overlay of painful events that could
result in pain chronicity.
PMID- 28420943
TI - Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived
Neurotrophic Factor Expression in the Central Nervous System in Rats with
Neuropathic Pain Induced by CCI in Rats.
AB - Background. Glial cells are implicated in the development of chronic pain and
brain-derived neurotropic factor (BDNF) released from activated microglia
contributes to the nociceptive transmission. Neural mobilization (NM) technique
is a method clinically effective in reducing pain sensitivity. Here we examined
the involvement of glial cells and BDNF expression in the thalamus and midbrain
after NM treatment in rats with chronic constriction injury (CCI). CCI was
induced and rats were subsequently submitted to 10 sessions of NM, every other
day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial
fibrillary acidic protein (GFAP), microglial cell OX-42, and BDNF using
Immunohistochemistry and Western blot assays. Results. Thalamus and midbrain of
CCI group showed increases in GFAP, OX-42, and BDNF expression compared with
control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after
NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42,
and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal
gray in midbrain was shown by immunohistochemistry. Conclusions. These findings
may improve the knowledge about the involvement of astrocytes, microglia, and
BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic
pain, affects glial cells and BDNF expression.
PMID- 28420944
TI - New Therapies for Hepatitis C Virus Infection.
AB - Approximately 350 million people worldwide are infected with hepatitis C virus
(HCV), which is associated with morbidity and mortality related to cirrhosis,
hepatocellular carcinoma, or liver failure. Recently, vast improvements have been
made with the development of direct-acting antiviral (DAA) agents, which are all
oral, are better tolerated than interferon-based treatment, and provide a
sustained virologic response in more than 90% of treated patients. This article
reviews the new therapies available for HCV infection, with a focus on patients
who have chronic HCV with and without compensated cirrhosis. As DAA development
continues, more attention will need to be given to special patient populations,
specifically to patients who fail treatment due to emerging resistant strains.
Considerable challenges yet to be overcome are incremental diagnosis of
unidentified patients and linkage to care that is affordable and available to all
patients.
PMID- 28420945
TI - Controversies and Recent Developments of the Low-FODMAP Diet.
AB - The low-fermentable oligo-, di-, and monosaccharide and polyol (FODMAP) diet is a
2-phased intervention, with strict reduction of all slowly absorbed or
indigestible short-chain carbohydrates (ie, FODMAPs) followed by reintroduction
of specific FODMAPs according to tolerance. The efficacy of the elimination phase
of the FODMAP diet is well established, but the success of maintaining this diet
has been shown in only a few observational studies. How the efficacy of the low
FODMAP diet compares with that of other therapies has received limited attention,
but recent studies have shown this diet to be comparable or superior to diets
that address eating style and choice of food as well as to gut hypnotherapy.
There has been no comparison between the low-FODMAP diet and the gluten-free
diet, which moderately reduces FODMAP intake. Mechanistically, dietary FODMAPs
have very limited effects on the consistency of bowel actions but seem to
suppress the release of histamine. Neither symptom pattern nor breath hydrogen
testing for fructose or polyol malabsorption is a useful predictor of efficacy,
but analysis of gut microbiota has potential. As a restrictive diet, the low
FODMAP diet carries risks of nutritional inadequacy and of fostering disordered
eating, which has received little attention. Strict FODMAP restriction induces a
potentially unfavorable gut microbiota, although the impact of this consequence
upon health is unknown. This observation puts additional impetus on the
reintroduction of FODMAPs according to tolerance during the maintenance phase of
the diet. Studies of the low-FODMAP diet in children are few but do suggest
benefit. However, such a strategy should be implemented with care due to the
psychological and nutritional risks of a restrictive diet. Clinical wisdom is
required in utilizing the low-FODMAP diet.
PMID- 28420946
TI - An Overview of Transoral Incisionless Fundoplication and Magnetic Sphincter
Augmentation for GERD.
PMID- 28420947
TI - The Use of Fecal Calprotectin in Inflammatory Bowel Disease.
PMID- 28420948
TI - Nonradiation, Endoscopic Ultrasound-Based Endoscopic Retrograde
Cholangiopancreatography.
PMID- 28420949
TI - Removal of Zinc from Aqueous Solution by Optimized Oil Palm Empty Fruit Bunches
Biochar as Low Cost Adsorbent.
AB - This study aims to produce optimized biochar from oil palm empty fruit bunches
(OPEFB), as a green, low cost adsorbent for uptake of zinc from aqueous solution.
The impact of pyrolysis conditions, namely, highest treatment temperature (HTT),
heating rate (HR), and residence time (RT) on biochar yield and adsorption
capacity towards zinc, was investigated. Mathematical modeling and optimization
of independent variables were performed employing response surface methodology
(RSM). HTT was found to be the most influential variable, followed by residence
time and heating rate. Based on the central composite design (CCD), two quadratic
models were developed to correlate three independent variables to responses. The
optimum production condition for OPEFB biochar was found as follows: HTT of 615
degrees C, HR of 8 degrees C/min, and RT of 128 minutes. The optimum biochar
showed 15.18 mg/g adsorption capacity for zinc and 25.49% of yield which was in
agreement with the predicted values, satisfactory. Results of the
characterization of optimum product illustrated well-developed BET surface area
and porous structure in optimum product which favored its sorptive ability.
PMID- 28420950
TI - Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies.
AB - Metallothioneins (MTs) are proteins that function by metal exchange to regulate
the bioavailability of metals, such as zinc and copper. Copper functions in the
brain to regulate mitochondria, neurotransmitter production, and cell signaling.
Inappropriate copper binding can result in loss of protein function and
Cu(I)/(II) redox cycling can generate reactive oxygen species. Copper accumulates
in the brain with aging and has been shown to bind alpha-synuclein and initiate
its aggregation, the primary aetiological factor in Parkinson's disease (PD), and
other alpha-synucleinopathies. In PD, total tissue copper is decreased, including
neuromelanin-bound copper and there is a reduction in copper transporter CTR-1.
Conversely cerebrospinal fluid (CSF) copper is increased. MT-1/2 expression is
increased in activated astrocytes in alpha-synucleinopathies, yet expression of
the neuronal MT-3 isoform may be reduced. MTs have been implicated in
inflammatory states to perform one-way exchange of copper, releasing free zinc
and recent studies have found copper bound to alpha-synuclein is transferred to
the MT-3 isoform in vitro and MT-3 is found bound to pathological alpha-synuclein
aggregates in the alpha-synucleinopathy, multiple systems atrophy. Moreover, both
MT and alpha-synuclein can be released and taken up by neural cells via specific
receptors and so may interact both intra- and extra-cellularly. Here, we
critically review the role of MTs in copper dyshomeostasis and alpha-synuclein
aggregation, and their potential as biomarkers and therapeutic targets.
PMID- 28420951
TI - Shared Neural Mechanisms for the Prediction of Own and Partner Musical Sequences
after Short-term Piano Duet Training.
AB - Predictive mechanisms in the human brain can be investigated using markers for
prediction violations like the mismatch negativity (MMN). Short-term piano
training increases the MMN for melodic and rhythmic deviations in the training
material. This increase occurs only when the material is actually played, not
when it is only perceived through listening, suggesting that learning predictions
about upcoming musical events are derived from motor involvement. However, music
is often performed in concert with others. In this case, predictions about
upcoming actions from a partner are a crucial part of the performance. In the
present experiment, we use magnetoencephalography (MEG) to measure MMNs to
deviations in one's own and a partner's musical material after both engaged in
musical duet training. Event-related field (ERF) results revealed that the MMN
increased significantly for own and partner material suggesting a neural
representation of the partner's part in a duet situation. Source analysis using
beamforming revealed common activations in auditory, inferior frontal, and
parietal areas, similar to previous results for single players, but also a
pronounced contribution from the cerebellum. In addition, activation of the
precuneus and the medial frontal cortex was observed, presumably related to the
need to distinguish between own and partner material.
PMID- 28420952
TI - Motion-Induced Position Shifts Activate Early Visual Cortex.
AB - The ability to correctly determine the position of objects in space is a
fundamental task of the visual system. The perceived position of briefly
presented static objects can be influenced by nearby moving contours, as
demonstrated by various illusions collectively known as motion-induced position
shifts. Here we use a stimulus that produces a particularly strong effect of
motion on perceived position. We test whether several regions-of-interest (ROIs),
at different stages of visual processing, encode the perceived rather than
retinotopically veridical position. Specifically, we collect functional MRI data
while participants experience motion-induced position shifts and use a
multivariate pattern analysis approach to compare the activation patterns evoked
by illusory position shifts with those evoked by matched physical shifts. We find
that the illusory perceived position is represented at the earliest stages of the
visual processing stream, including primary visual cortex. Surprisingly, we found
no evidence of percept-based encoding of position in visual areas beyond area V3.
This result suggests that while it is likely that higher-level visual areas are
involved in position encoding, early visual cortex also plays an important role.
PMID- 28420954
TI - Multiple Kernel Based Region Importance Learning for Neural Classification of
Gait States from EEG Signals.
AB - With the development of Brain Machine Interface (BMI) systems, people with motor
disabilities are able to control external devices to help them restore movement
abilities. Longitudinal validation of these systems is critical not only to
assess long-term performance reliability but also to investigate adaptations in
electrocortical patterns due to learning to use the BMI system. In this paper, we
decode the patterns of user's intended gait states (e.g., stop, walk, turn left,
and turn right) from scalp electroencephalography (EEG) signals and
simultaneously learn the relative importance of different brain areas by using
the multiple kernel learning (MKL) algorithm. The region of importance (ROI) is
identified during training the MKL for classification. The efficacy of the
proposed method is validated by classifying different movement intentions from
two subjects-an able-bodied and a spinal cord injury (SCI) subject. The
preliminary results demonstrate that frontal and fronto-central regions are the
most important regions for the tested subjects performing gait movements, which
is consistent with the brain regions hypothesized to be involved in the control
of lower-limb movements. However, we observed some regional changes comparing the
able-bodied and the SCI subject. Moreover, in the longitudinal experiments, our
findings exhibit the cortical plasticity triggered by the BMI use, as the
classification accuracy and the weights for important regions-in sensor space
generally increased, as the user learned to control the exoskeleton for movement
over multiple sessions.
PMID- 28420953
TI - Using Cochlear Microphonic Potentials to Localize Peripheral Hearing Loss.
AB - The cochlear microphonic (CM) is created primarily by the receptor currents of
outer hair cells (OHCs) and may therefore be useful for identifying cochlear
regions with impaired OHCs. However, the CM measured across the frequency range
with round-window or ear-canal electrodes lacks place-specificity as it is
dominated by cellular sources located most proximal to the recording site (e.g.,
at the cochlear base). To overcome this limitation, we extract the "residual" CM
(rCM), defined as the complex difference between the CM measured with and without
an additional tone (saturating tone, ST). If the ST saturates receptor currents
near the peak of its excitation pattern, then the rCM should reflect the activity
of OHCs in that region. To test this idea, we measured round-window CMs in
chinchillas in response to low-level probe tones presented alone or with an ST
ranging from 1 to 2.6 times the probe frequency. CMs were measured both before
and after inducing a local impairment in cochlear function (a 4-kHz notch-type
acoustic trauma). Following the acoustic trauma, little change was observed in
the probe-alone CM. In contrast, rCMs were reduced in a frequency-specific
manner. When shifts in rCM levels were plotted vs. the ST frequency, they matched
well the frequency range of shifts in neural thresholds. These results suggest
that rCMs originate near the cochlear place tuned to the ST frequency and thus
can be used to assess OHC function in that region. Our interpretation of the data
is supported by predictions of a simple phenomenological model of CM generation
and two-tone interactions. The model indicates that the sensitivity of rCM to
acoustic trauma is governed by changes in cochlear response at the ST tonotopic
place rather than at the probe place. The model also suggests that a combination
of CM and rCM measurements could be used to assess both the site and etiology of
sensory hearing loss in clinical applications.
PMID- 28420955
TI - Hemispheric Differences in White Matter Microstructure between Two Profiles of
Children with High Intelligence Quotient vs. Controls: A Tract-Based Spatial
Statistics Study.
AB - Objectives: The main goal of this study was to investigate and compare the neural
substrate of two children's profiles of high intelligence quotient (HIQ).
Methods: Two groups of HIQ children were included with either a homogeneous (Hom
HIQ: n = 20) or a heterogeneous IQ profile (Het-HIQ: n = 24) as defined by a
significant difference between verbal comprehension index and perceptual
reasoning index. Diffusion tensor imaging was used to assess white matter (WM)
microstructure while tract-based spatial statistics (TBSS) analysis was performed
to detect and localize WM regional differences in fractional anisotropy (FA),
mean diffusivity, axial (AD), and radial diffusivities. Quantitative measurements
were performed on 48 regions and 21 fiber-bundles of WM. Results: Hom-HIQ
children presented higher FA than Het-HIQ children in widespread WM regions
including central structures, and associative intra-hemispheric WM fasciculi. AD
was also greater in numerous WM regions of Total-HIQ, Hom-HIQ, and Het-HIQ groups
when compared to the Control group. Hom-HIQ and Het-HIQ groups also differed by
their hemispheric lateralization in AD differences compared to Controls. Het-HIQ
and Hom-HIQ groups showed a lateralization ratio (left/right) of 1.38 and 0.78,
respectively. Conclusions: These findings suggest that both inter- and intra
hemispheric WM integrity are enhanced in HIQ children and that neural substrate
differs between Hom-HIQ and Het-HIQ. The left hemispheric lateralization of Het
HIQ children is concordant with their higher verbal index while the relative
right hemispheric lateralization of Hom-HIQ children is concordant with their
global brain processing and adaptation capacities as evidenced by their
homogeneous IQ.
PMID- 28420956
TI - Retinal Gene Therapy: Surgical Vector Delivery in the Translation to Clinical
Trials.
AB - An exceptionally high number of monogenic disorders lead to incurable blindness,
making them targets for the development of gene-therapy. In order to successfully
apply therapeutic vector systems in vivo, the heterogeneity of the disease
phenotype needs to be considered. This necessitates tailored approaches such as
subretinal or intravitreal injections with the aim to maximize transduction of
target cell populations, while minimizing off-target effects and surgical
complications. Strategic decisions on parameters of the application are crucial
to obtain the best treatment outcomes and patient safety. While most of the
current retinal gene therapy trials utilize a subretinal approach, a deeper
understanding of the numerous factors and considerations in choosing one delivery
approach over the other for various ocular pathologies could lead to an improved
safety and treatment efficacy. In this review we survey different vector
injection techniques and parameters applied in recent retinal (pre-)clinical
trials. We explore the advantages and shortcomings of each delivery strategy in
the setting of different underlying ocular pathologies and other relevant
factors. We highlight the potential benefits for patient safety and efficacy in
applying those considerations in the decision making process.
PMID- 28420957
TI - Neuropeptide Y-Induced Orexigenic Action Is Attenuated by the Orexin Receptor
Antagonist in Bullfrog Larvae.
AB - In bullfrog larvae at the pre- and pro-metamorphic stages, feeding behavior is
regulated by appetite factors such as orexigenic peptides. In fact, food intake
is enhanced by intracerebroventricular (ICV) administration of neuropeptide Y
(NPY) and orexin A. Using goldfish, our previous study indicated that the
orexigenic action of NPY is mediated by orexin A, suggesting the functional
interaction between the two. However, there is little information about whether
the action of orexin A mediates the orexigenic action of NPY in bullfrog larvae.
Therefore, we examined the effect of the orexin receptor antagonist, SB334867 on
the orexigenic action of NPY in larvae. The stimulatory effect of ICV injection
of NPY at 10 pmol/g body weight (BW) on food intake was abolished by treatment
with SB334867 at 60 pmol/g BW. These results suggest that, in bullfrog larvae,
there is a neuronal relationship between the NPY and orexin systems, and that the
orexigenic action of NPY is mediated by the orexin A-induced orexigenic action.
PMID- 28420958
TI - Electrical Stimulation of Afferent Pathways for the Suppression of Pathological
Tremor.
AB - Pathological tremors are involuntary oscillatory movements which cannot be fully
attenuated using conventional treatments. For this reason, several studies have
investigated the use of neuromuscular electrical stimulation for tremor
suppression. In a recent study, however, we found that electrical stimulation
below the motor threshold also suppressed tremor, indicating involvement of
afferent pathways. In this study, we further explored this possibility by
systematically investigating how tremor suppression by afferent stimulation
depends on the stimulation settings. In this way, we aimed at identifying the
optimal stimulation strategy, as well as to elucidate the underlying
physiological mechanisms of tremor suppression. Stimulation strategies varying
the stimulation intensity and pulse timing were tested in nine tremor patients
using either intramuscular or surface stimulation. Significant tremor suppression
was observed in six patients (tremor suppression > 75% was observed in three
patients) and the average optimal suppression level observed across all subjects
was 52%. The efficiency for each stimulation setting, however, varied
substantially across patients and it was not possible to identify a single set of
stimulation parameters that yielded positive results in all patients. For
example, tremor suppression was achieved both with stimulation delivered in an
out-of-phase pattern with respect to the tremor, and with random timing of the
stimulation. Overall, these results indicate that low-current stimulation of
afferent fibers is a promising approach for tremor suppression, but that further
research is required to identify how the effect can be maximized in the
individual patient.
PMID- 28420959
TI - Transcranial Direct Current Stimulation Does Not Affect Lower Extremity Muscle
Strength Training in Healthy Individuals: A Triple-Blind, Sham-Controlled Study.
AB - The present study investigated the effects of anodal transcranial direct current
stimulation (tDCS) on lower extremity muscle strength training in 24 healthy
participants. In this triple-blind, sham-controlled study, participants were
randomly allocated to the anodal tDCS plus muscle strength training (anodal tDCS)
group or sham tDCS plus muscle strength training (sham tDCS) group. Anodal tDCS
(2 mA) was applied to the primary motor cortex of the lower extremity during
muscle strength training of the knee extensors and flexors. Training was
conducted once every 3 days for 3 weeks (7 sessions). Knee extensor and flexor
peak torques were evaluated before and after the 3 weeks of training. After the 3
week intervention, peak torques of knee extension and flexion changed from 155.9
to 191.1 Nm and from 81.5 to 93.1 Nm in the anodal tDCS group. Peak torques
changed from 164.1 to 194.8 Nm on extension and from 78.0 to 85.6 Nm on flexion
in the sham tDCS group. In both groups, peak torques of knee extension and
flexion significantly increased after the intervention, with no significant
difference between the anodal tDCS and sham tDCS groups. In conclusion, although
the administration of eccentric training increased knee extensor and flexor peak
torques, anodal tDCS did not enhance the effects of lower extremity muscle
strength training in healthy individuals. The present null results have crucial
implications for selecting optimal stimulation parameters for clinical trials.
PMID- 28420960
TI - Contralateral Inhibition of Click- and Chirp-Evoked Human Compound Action
Potentials.
AB - Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal
auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit
provides the neural substrate for the MOC reflex, which inhibits cochlear
amplifier gain and is believed to play a role in listening in noise and
protection from acoustic overexposure. The human MOC reflex has been studied
extensively using otoacoustic emissions (OAE) paradigms; however, these
measurements are insensitive to subsequent "downstream" efferent effects on the
neural ensembles that mediate hearing. In this experiment, click- and chirp
evoked auditory nerve compound action potential (CAP) amplitudes were measured
electrocochleographically from the human eardrum without and with MOC reflex
activation elicited by contralateral broadband noise. We hypothesized that the
chirp would be a more optimal stimulus for measuring neural MOC effects because
it synchronizes excitation along the entire length of the basilar membrane and
thus evokes a more robust CAP than a click at low to moderate stimulus levels.
Chirps produced larger CAPs than clicks at all stimulus intensities (50-80 dB
ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low
stimulus levels when quantified both in terms of amplitude reduction and
effective attenuation. Effective attenuation was larger for chirp- and click
evoked CAPs than for click-evoked OAEs measured from the same subjects. Our
results suggest that the chirp is an optimal stimulus for evoking CAPs at low
stimulus intensities and for assessing MOC reflex effects on the auditory nerve.
Further, our work supports previous findings that MOC reflex effects at the level
of the auditory nerve are underestimated by measures of OAE inhibition.
PMID- 28420961
TI - The Role of Astrocytes in Neuroprotection after Brain Stroke: Potential in Cell
Therapy.
AB - Astrocytes are commonly involved in negative responses through their
hyperreactivity and glial scar formation in excitotoxic and/or mechanical
injuries. But, astrocytes are also specialized glial cells of the nervous system
that perform multiple homeostatic functions for the survival and maintenance of
the neurovascular unit. Astrocytes have neuroprotective, angiogenic,
immunomodulatory, neurogenic, and antioxidant properties and modulate synaptic
function. This makes them excellent candidates as a source of neuroprotection and
neurorestoration in tissues affected by ischemia/reperfusion, when some of their
deregulated genes can be controlled. Therefore, this review analyzes pro-survival
responses of astrocytes that would allow their use in cell therapy strategies.
PMID- 28420962
TI - Dysregulation of RNA Binding Protein Aggregation in Neurodegenerative Disorders.
AB - The unique biology of RNA binding proteins is altering our view of the genesis of
protein misfolding diseases. These proteins use aggregation of low complexity
domains (LCDs) as a means to regulate the localization and utilization of RNA by
forming RNA granules, such as stress granules, transport granules and P-bodies.
The reliance on reversible aggregation as a mechanism for biological regulation
renders this family of proteins highly vulnerable to promoting diseases of
protein misfolding. Mutations in RNA binding proteins are associated with many
neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and
frontotemporal lobar dementia (FTLD). The biology of RNA binding proteins also
extends to microtubule associated protein tau. Tau is normally an axonal protein,
but in stress it translocates to the somatodendritic arbor where it takes on a
new function promoting formation of stress granules. The interaction of tau with
stress granules also promotes tau aggregation, accelerating formation of the tau
pathology that we associate with diseases such as Alzheimer's disease (AD).
PMID- 28420963
TI - RNA-Seq Analysis of Microglia Reveals Time-Dependent Activation of Specific
Genetic Programs following Spinal Cord Injury.
AB - Neurons have inherent competence to regrow following injury, although not
spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation
driven by resident microglia and infiltrating peripheral macrophages. Microglia
are the first reactive glial population after SCI and participate in recruitment
of monocyte-derived macrophages to the lesion site. Both positive and negative
influence of microglia and macrophages on axonal regeneration had been reported
after SCI, raising the issue whether their response depends on time post-lesion
or different lesion severity. We analyzed molecular alterations in microglia at
several time-points after different SCI severities using RNA-sequencing. We
demonstrate that activation of microglia is time-dependent post-injury but is
independent of lesion severity. Early transcriptomic response of microglia after
SCI involves proliferation and neuroprotection, which is then switched to
neuroinflammation at later stages. Moreover, SCI induces an autologous microglial
expression of astrocytic markers with over 6% of microglia expressing glial
fibrillary acidic protein and vimentin from as early as 72 h post-lesion and up
to 6 weeks after injury. We also identified the potential involvement of DNA
damage and in particular tumor suppressor gene breast cancer susceptibility gene
1 (Brca1) in microglia after SCI. Finally, we established that BRCA1 protein is
specifically expressed in non-human primate spinal microglia and is upregulated
after SCI. Our data provide the first transcriptomic analysis of microglia at
multiple stages after different SCI severities. Injury-induced microglia
expression of astrocytic markers at RNA and protein levels demonstrates novel
insights into microglia plasticity. Finally, increased microglia expression of
BRCA1 in rodents and non-human primate model of SCI, suggests the involvement of
oncogenic proteins after CNS lesion.
PMID- 28420964
TI - Identification of the Spinal Expression Profile of Non-coding RNAs Involved in
Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.
AB - Neuropathic pain (NP) is caused by damage to the nervous system, resulting in
aberrant pain, which is associated with gene expression changes in the sensory
pathway. However, the molecular mechanisms are not fully understood. A non-coding
Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a
protein. NcRNAs are involved in many cellular processes, and mutations or
imbalances of the repertoire within the body can cause a variety of diseases.
Although ncRNAs have recently been shown to play a role in NP pathogenesis, the
specific effects of ncRNAs in NP remain largely unknown. In this study,
sequencing analysis was performed to investigated the expression patterns of
ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of
134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs
(circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared
nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain
reaction (PCR) was performed to validate the expression of selected lncRNAs,
miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to
explore the potential ncRNA functions and relationships. Our data showed that the
most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt
signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and
protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA
miRNA-mRNA network of NP was constructed. This is the first study to
comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate
the involvement of different ncRNA expression patterns in the spinal cord of NP
pathogenesis by sequence analysis. This information will enable further research
on the pathogenesis of NP and facilitate the development of novel NP therapeutics
targeting ncRNAs.
PMID- 28420966
TI - Fast and Slow Inhibition in the Visual Thalamus Is Influenced by Allocating GABAA
Receptors with Different gamma Subunits.
AB - Cell-type specific differences in the kinetics of inhibitory postsynaptic
conductance changes (IPSCs) are believed to impact upon network dynamics
throughout the brain. Much attention has focused on how GABAA receptor (GABAAR)
alpha and beta subunit diversity will influence IPSC kinetics, but less is known
about the influence of the gamma subunit. We have examined whether GABAAR gamma
subunit heterogeneity influences IPSC properties in the thalamus. The gamma2
subunit gene was deleted from GABAARs selectively in the dorsal lateral
geniculate nucleus (dLGN). The removal of the gamma2 subunit from the dLGN
reduced the overall spontaneous IPSC (sIPSC) frequency across all relay cells and
produced an absence of IPSCs in a subset of relay neurons. The remaining slower
IPSCs were both insensitive to diazepam and zinc indicating the absence of the
gamma2 subunit. Because these slower IPSCs were potentiated by methyl-6,7
dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), we propose these IPSCs
involve gamma1 subunit-containing GABAAR activation. Therefore, gamma subunit
heterogeneity appears to influence the kinetics of GABAAR-mediated synaptic
transmission in the visual thalamus in a cell-selective manner. We suggest that
activation of gamma1 subunit-containing GABAARs give rise to slower IPSCs in
general, while faster IPSCs tend to be mediated by gamma2 subunit-containing
GABAARs.
PMID- 28420965
TI - Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System.
AB - Circadian rhythms are daily rhythms that regulate many biological processes -
from gene transcription to behavior - and a disruption of these rhythms can lead
to a myriad of health risks. Circadian rhythms are entrained by light, and their
24-h oscillation is maintained by a core molecular feedback loop composed of
canonical circadian ("clock") genes and proteins. Different modulators help to
maintain the proper rhythmicity of these genes and proteins, and one emerging
modulator is dopamine. Dopamine has been shown to have circadian-like activities
in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it
regulates, and is regulated by, clock genes in some of these areas. Thus, it is
likely that dopamine is essential to mechanisms that maintain proper rhythmicity
of these five brain areas. This review discusses studies that showcase different
dopaminergic mechanisms that may be involved with the regulation of these brain
areas' circadian rhythms. Mechanisms include how dopamine and dopamine receptor
activity directly and indirectly influence clock genes and proteins, how
dopamine's interactions with gap junctions influence daily neuronal excitability,
and how dopamine's release and effects are gated by low- and high-pass filters.
Because the dopamine neurons described in this review also release the inhibitory
neurotransmitter GABA which influences clock protein expression in the retina, we
discuss articles that explore how GABA may contribute to the actions of dopamine
neurons on circadian rhythms. Finally, to understand how the loss of function of
dopamine neurons could influence circadian rhythms, we review studies linking the
neurodegenerative disease Parkinson's Disease to disruptions of circadian rhythms
in these five brain areas. The purpose of this review is to summarize growing
evidence that dopamine is involved in regulating circadian rhythms, either
directly or indirectly, in the brain areas discussed here. An appreciation of the
growing evidence of dopamine's influence on circadian rhythms may lead to new
treatments including pharmacological agents directed at alleviating the various
symptoms of circadian rhythm disruption.
PMID- 28420967
TI - Organization and Plasticity of Sodium Channel Expression in the Mouse Olfactory
and Vomeronasal Epithelia.
AB - To understand the molecular basis of neuronal excitation in the mammalian
olfactory system, we conducted a systematic analysis of the organization of
voltage-gated sodium (Nav) channel subunits in the main olfactory epithelium
(MOE) and vomeronasal organ (VNO) of adult mice. We also analyzed changes in Nav
channel expression during development in these two systems and during
regeneration of the MOE. Quantitative PCR shows that Nav1.7 is the predominant
isoform in both adult MOE and VNO. We detected pronounced immunoreactivity for
Nav1.7 and Nav1.3 in axons of olfactory and vomeronasal sensory neurons (VSNs).
Analysis of Nav1.2 and Nav1.6 revealed an unexpected subsystem-specific
distribution. In the MOE, these Nav channels are absent from olfactory sensory
neurons (OSNs) but present in non-neuronal olfactory cell types. In the VNO,
Nav1.2 and Nav1.6 are confined to VSNs, with Nav1.2-immunoreactive somata solely
present in the basal layer of the VNO. The subcellular localization of Nav1.3 and
Nav1.7 in OSNs can change dramatically during periods of heightened plasticity in
the MOE. During the first weeks of development and during regeneration of the
olfactory epithelium following chemical lesion, expression of Nav1.3 and Nav1.7
is transiently enhanced in the somata of mature OSNs. Our results demonstrate a
highly complex organization of Nav channel expression in the mouse olfactory
system, with specific commonalities but also differences between the MOE and the
VNO. On the basis of their subcellular localization, Nav1.3 and Nav1.7 should
play major roles in action potential propagation in both MOE and VNO, whereas
Nav1.2 and Nav1.6 are specific to the function of VSNs. The plasticity of Nav
channel expression in OSNs during early development and recovery from injury
could reflect important physiological requirements in a variety of activity
dependent mechanisms.
PMID- 28420968
TI - Cortical Variability and Challenges for Modeling Approaches.
PMID- 28420969
TI - Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB
Rat Line.
AB - This review article addresses the biological factors that influence: (i) the
acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake;
and (iii) alcohol relapse-like drinking behavior in animals bred for their high
ethanol intake. Data from several rat strains/lines strongly suggest that
catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute
requirement (up 80%-95%) for rats to display ethanol's reinforcing effects and to
initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine
forming salsolinol, a compound that is self-administered. In UChB rats,
salsolinol: (a) generates marked sensitization to the motivational effects of
ethanol; and (b) strongly promotes binge-like drinking. The specificity of
salsolinol actions is shown by the finding that only the R-salsolinol enantiomer
but not S-salsolinol accounted for the latter effects. Inhibition of brain
acetaldehyde synthesis does not influence the maintenance of chronic ethanol
intake. However, a prolonged ethanol withdrawal partly returns the requirement
for acetaldehyde synthesis/levels both on chronic ethanol intake and on alcohol
relapse-like drinking. Chronic ethanol intake, involving the action of
lipopolysaccharide diffusing from the gut, and likely oxygen radical generated
upon catechol/salsolinol oxidation, leads to oxidative stress and neuro
inflammation, known to potentiate each other. Data show that the administration
of N-acetyl cysteine (NAC) a strong antioxidant inhibits chronic ethanol
maintenance by 60%-70%, without inhibiting its initial intake. Intra
cerebroventricular administration of mesenchymal stem cells (MSCs), known to
release anti-inflammatory cytokines, to elevate superoxide dismutase levels and
to reverse ethanol-induced hippocampal injury and cognitive deficits, also
inhibited chronic ethanol maintenance; further, relapse-like ethanol drinking was
inhibited up to 85% for 40 days following intracerebral stem cell administration.
Thus: (i) ethanol must be metabolized intracerebrally into acetaldehyde, and
further into salsolinol, which appear responsible for promoting the acquisition
of the early reinforcing effects of ethanol; (ii) acetaldehyde is not responsible
for the maintenance of chronic ethanol intake, while other mechanisms are
indicated; (iii) the systemic administration of NAC, a strong antioxidant
markedly inhibits the maintenance of chronic ethanol intake; and (iv) the intra
cerebroventricular administration of anti-inflammatory and antioxidant MSCs
inhibit both the maintenance of chronic ethanol intake and relapse-like drinking.
PMID- 28420970
TI - Single-Session Anodal tDCS with Small-Size Stimulating Electrodes Over
Frontoparietal Superficial Sites Does Not Affect Motor Sequence Learning.
AB - Due to the potential of anodal transcranial direct current stimulation (a-tDCS)
for enhancement of fine sequenced movements and increasing interest in achieving
high level of fine movements in the trained and untrained hands especially at
initial stage of learning, we designed this study to investigate whether the
application of single-session a-tDCS with small-size stimulating electrodes over
FPN sites, such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex
(M1) or posterior parietal cortex (PPC) could enhance sequence learning with the
trained hand and these effects are transferred into the untrained hand or not. A
total of 51 right-handed healthy participants were randomly assigned to one of
the four stimulation groups: a-tDCS of left M1, DLPFC, PPC, or sham. Stimulation
was applied for 20 min during a sequential visual isometric pinch task (SVIPT).
Eight blocks of training using SVIPT were completed with the right hand during
stimulation. Two blocks of sequence training with each hand were performed by
participants as assessment blocks at three time points: baseline, 15 min and one
day following the intervention. Behavioral outcomes including movement time,
error rate and skill were assessed in all assessment blocks across three time
points. We also measured corticospinal excitability, short-interval intracortical
inhibition, and intracortical facilitation using single- and paired-pulse
transcranial magnetic stimulation. The results indicated that the behavioral
outcomes were significantly improved with the right trained hand, but this
learning effect was not modulated by a-tDCS with small-size stimulating
electrodes over the FPN. Transfer of learning into the untrained hand was
observed in all four groups for movement time but not for the error rate or
skill. Our results suggest that sequential learning in SVIPT and its transfer
into the untrained hand were not sensitive to a single-session a-tDCS with small
size stimulating electrodes over left M1, DLPFC or PPC in young healthy
participants.
PMID- 28420971
TI - Dynamic Increase in Corticomuscular Coherence during Bilateral, Cyclical Ankle
Movements.
AB - In humans, the midline primary motor cortex is active during walking. However,
the exact role of such cortical participation is unknown. To delineate the role
of the primary motor cortex in walking, we examined whether the primary motor
cortex would activate leg muscles during movements that retained specific
requirements of walking (i.e., locomotive actions). We recorded
electroencephalographic and electromyographic signals from 15 healthy, young men
while they sat and performed bilateral, cyclical ankle movements. During
dorsiflexion, near-20-Hz coherence increased cyclically between the midline
primary motor cortex and the co-contracting antagonistic pair (i.e., tibialis
anterior and medial gastrocnemius muscles) in both legs. Thus, we have shown that
dynamic increase in corticomuscular coherence, which has been observed during
walking, also occurs during simple bilateral cyclical movements of the feet. A
possible mechanism for such coherence is corticomuscular communication, in which
the primary motor cortex participates in the control of movement. Furthermore,
because our experimental task isolated certain locomotive actions, the observed
coherence suggests that the human primary motor cortex may participate in these
actions (i.e., maintaining a specified movement frequency, bilaterally
coordinating the feet, and stabilizing the posture of the feet). Additional
studies are needed to identify the exact cortical and subcortical interactions
that cause corticomuscular coherence and to further delineate the functional role
of the primary motor cortex during bilateral cyclical movements such as walking.
PMID- 28420972
TI - Multi-modal, Multi-measure, and Multi-class Discrimination of ADHD with
Hierarchical Feature Extraction and Extreme Learning Machine Using Structural and
Functional Brain MRI.
AB - Structural and functional MRI unveil many hidden properties of the human brain.
We performed this multi-class classification study on selected subjects from the
publically available attention deficit hyperactivity disorder ADHD-200 dataset of
patients and healthy children. The dataset has three groups, namely, ADHD
inattentive, ADHD combined, and typically developing. We calculated the global
averaged functional connectivity maps across the whole cortex to extract
anatomical atlas parcellation based features from the resting-state fMRI (rs
fMRI) data and cortical parcellation based features from the structural MRI
(sMRI) data. In addition, the preprocessed image volumes from both of these
modalities followed an ANOVA analysis separately using all the voxels. This study
utilized the average measure from the most significant regions acquired from
ANOVA as features for classification in addition to the multi-modal and multi
measure features of structural and functional MRI data. We extracted most
discriminative features by hierarchical sparse feature elimination and selection
algorithm. These features include cortical thickness, image intensity, volume,
cortical thickness standard deviation, surface area, and ANOVA based features
respectively. An extreme learning machine performed both the binary and multi
class classifications in comparison with support vector machines. This article
reports prediction accuracy of both unimodal and multi-modal features from test
data. We achieved 76.190% (p < 0.0001) classification accuracy in multi-class
settings as well as 92.857% (p < 0.0001) classification accuracy in binary
settings. In addition, we found ANOVA-based significant regions of the brain that
also play a vital role in the classification of ADHD. Thus, from a clinical
perspective, this multi-modal group analysis approach with multi-measure features
may improve the accuracy of the ADHD differential diagnosis.
PMID- 28420973
TI - No Overt Effects of a 6-Week Exergame Training on Sensorimotor and Cognitive
Function in Older Adults. A Preliminary Investigation.
AB - Several studies investigating the relationship between physical activity and
cognition showed that exercise interventions might have beneficial effects on
working memory, executive functions as well as motor fitness in old adults.
Recently, movement based video games (exergames) have been introduced to have the
capability to improve cognitive function in older adults. Healthy aging is
associated with a loss of cognitive, as well as sensorimotor functions. During
exergaming, participants are required to perform physical activities while being
simultaneously surrounded by a cognitively challenging environment. However, only
little is known about the impact of exergame training interventions on a broad
range of motor, sensory, and cognitive skills. Therefore, the present study aims
at investigating the effects of an exergame training over 6 weeks on cognitive,
motor, and sensory functions in healthy old participants. For this purpose, 30
neurologically healthy older adults were randomly assigned to either an
experimental (ETG, n = 15, 1 h training, twice a week) or a control group (NTG, n
= 15, no training). Several cognitive tests were performed before and after
exergaming in order to capture potential training-induced effects on processing
speed as well as on executive functions. To measure the impact of exergaming on
sensorimotor performance, a test battery consisting of pinch and grip force of
the hand, tactile acuity, eye-hand coordination, flexibility, reaction time,
coordination, and static balance were additionally performed. While we observed
significant improvements in the trained exergame (mainly in tasks that required a
high load of coordinative abilities), these gains did not result in differential
performance improvements when comparing ETG and NTG. The only exergaming-induced
difference was a superior behavioral gain in fine motor skills of the left hand
in ETG compared to NTG. In an exploratory analysis, within-group comparison
revealed improvements in sensorimotor and cognitive tasks (ETG) while NTG only
showed an improvement in a static balance test. Taken together, the present study
indicates that even though exergames might improve gaming performance, our
behavioral assessment was probably not sensitive enough to capture exergaming
induced improvements. Hence, we suggest to use more tailored outcome measures in
future studies to assess potential exergaming-induced changes.
PMID- 28420974
TI - Thinking on Treating Echolalia in Aphasia: Recommendations and Caveats for Future
Research Directions.
PMID- 28420976
TI - Improving Robot Motor Learning with Negatively Valenced Reinforcement Signals.
AB - Both nociception and punishment signals have been used in robotics. However, the
potential for using these negatively valenced types of reinforcement learning
signals for robot learning has not been exploited in detail yet. Nociceptive
signals are primarily used as triggers of preprogrammed action sequences.
Punishment signals are typically disembodied, i.e., with no or little relation to
the agent-intrinsic limitations, and they are often used to impose behavioral
constraints. Here, we provide an alternative approach for nociceptive signals as
drivers of learning rather than simple triggers of preprogrammed behavior.
Explicitly, we use nociception to expand the state space while we use punishment
as a negative reinforcement learning signal. We compare the performance-in terms
of task error, the amount of perceived nociception, and length of learned action
sequences-of different neural networks imbued with punishment-based reinforcement
signals for inverse kinematic learning. We contrast the performance of a version
of the neural network that receives nociceptive inputs to that without such a
process. Furthermore, we provide evidence that nociception can improve learning
making the algorithm more robust against network initializations-as well as
behavioral performance by reducing the task error, perceived nociception, and
length of learned action sequences. Moreover, we provide evidence that
punishment, at least as typically used within reinforcement learning
applications, may be detrimental in all relevant metrics.
PMID- 28420977
TI - Development and Training of a Neural Controller for Hind Leg Walking in a Dog
Robot.
AB - Animals dynamically adapt to varying terrain and small perturbations with
remarkable ease. These adaptations arise from complex interactions between the
environment and biomechanical and neural components of the animal's body and
nervous system. Research into mammalian locomotion has resulted in several neural
and neuro-mechanical models, some of which have been tested in simulation, but
few "synthetic nervous systems" have been implemented in physical hardware models
of animal systems. One reason is that the implementation into a physical system
is not straightforward. For example, it is difficult to make robotic actuators
and sensors that model those in the animal. Therefore, even if the sensorimotor
circuits were known in great detail, those parameters would not be applicable and
new parameter values must be found for the network in the robotic model of the
animal. This manuscript demonstrates an automatic method for setting parameter
values in a synthetic nervous system composed of non-spiking leaky integrator
neuron models. This method works by first using a model of the system to
determine required motor neuron activations to produce stable walking. Parameters
in the neural system are then tuned systematically such that it produces similar
activations to the desired pattern determined using expected sensory feedback. We
demonstrate that the developed method successfully produces adaptive locomotion
in the rear legs of a dog-like robot actuated by artificial muscles. Furthermore,
the results support the validity of current models of mammalian locomotion. This
research will serve as a basis for testing more complex locomotion controllers
and for testing specific sensory pathways and biomechanical designs.
Additionally, the developed method can be used to automatically adapt the neural
controller for different mechanical designs such that it could be used to control
different robotic systems.
PMID- 28420975
TI - Beta Band Corticomuscular Drive Reflects Muscle Coordination Strategies.
AB - During force production, hand muscle activity is known to be coherent with
activity in primary motor cortex, specifically in the beta-band (15-30 Hz)
frequency range. It is not clear, however, if this coherence reflects the control
strategy selected by the nervous system for a given task, or if it instead
reflects an intrinsic property of cortico-spinal communication. Here, we measured
corticomuscular and intermuscular coherence between muscles of index finger and
thumb while a two-finger pinch grip of identical net force was applied to objects
which were either stable (allowing synergistic activation of finger muscles) or
unstable (requiring individuated finger control). We found that beta-band
corticomuscular coherence with the first dorsal interosseous (FDI) and abductor
pollicis brevis (APB) muscles, as well as their beta-band coherence with each
other, was significantly reduced when individuated control of the thumb and index
finger was required. We interpret these findings to show that beta-band coherence
is reflective of a synergistic control strategy in which the cortex binds task
related motor neurons into functional units.
PMID- 28420978
TI - Resting State fMRI Reveals Increased Subthalamic Nucleus and Sensorimotor Cortex
Connectivity in Patients with Parkinson's Disease under Medication.
AB - Functional connectivity (FC) between the subthalamic nucleus (STN) and the
sensorimotor cortex is increased in off-medication patients with Parkinson's
disease (PD). However, the status of FC between STN and sensorimotor cortex in on
medication PD patients remains unclear. In this study, resting state functional
magnetic resonance imaging was employed on 31 patients with PD under medication
and 31 healthy controls. Two-sample t-test was used to study the change in FC
pattern of the STN, the FC strength of the bilateral STN was correlated with
overall motor symptoms, while unilateral STN was correlated with offside motor
symptoms. Both bilateral and right STN showed increased FC with the right
sensorimotor cortex, whereas only right STN FC was correlated with left-body
rigidity scores in all PD patients. An additional subgroup analysis was performed
according to the ratio of mean tremor scores and mean postural instability and
gait difficulty (PIGD) scores, only the PIGD subgroup showed the increased FC
between right STN and sensorimotor cortex under medication. Increased FC between
the STN and the sensorimotor cortex was found, which was related to motor symptom
severity in on-medication PD patients. Anti-PD drugs may influence the
hyperdirect pathway to alleviate motor symptoms with the more effect on the
tremor subtype.
PMID- 28420979
TI - Evidence for a Selectively Regulated Prioritization Shift Depending on Walking
Situations in Older Adults.
AB - Background: Older adults have increased risks of balance issues and falls when
walking and performing turns in daily situations. Changes of prioritization
during different walking situations associated with dual tasking may contribute
to these deficits. The objective of this study was therefore to investigate
whether older adults demonstrate changes of prioritization during different
walking paths. Methods: In total, 1,054 subjects with an age range from 50 to 83
years were selected from the first follow-up visit of the TREND (Tuebinger
evaluation of Risk factors for Early detection of Neurodegenerative Disorders)
study. They were classified according to their performance on the Trail Making
Test (TMT) into good and poor TMT performers (based on recent results showing
that cognitive flexibility affects prioritization strategies during straight
walking). Absolute dual-task performance and relative dual-task costs (DTC,
relative performance under dual-task conditions compared with single-task
conditions) were assessed in two paradigms: walking while subtracting serial 7 s
and walking while checking boxes on a clipboard. Both tasks were performed on
straight and curved paths. Results: Overall, the poor TMT performers group
performed worse in all single and dual tasks. Interestingly, the relative change
in performance measured by dual-task costs differed in the groups between the two
walking paths. On straight paths, poor TMT performers had a similar DTC of
walking to that of good performers (p = 0.10) but had a significantly lower DTC
of subtracting (p = 0.02). On curved paths, poor performers had a similar DTC of
subtracting (p = 0.10), but their DTC of walking was significantly higher (p <
0.0001). Conclusion: Given that walking on curved paths is considered more
difficult than that on straight paths and that the serial subtracting dual task
is more difficult than the box checking dual task, this study in older adults
provides evidence for the existence of a (walking) situation-dependent change of
prioritization. If confirmed in other studies, situation-dependent change of
prioritization should be included as a potential factor contributing to gait and
balance impairments, and increased fall risk in older adults.
PMID- 28420980
TI - Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration
in the Aging Human Retina.
AB - In mammals, melanopsin-expressing retinal ganglion cells (mRGCs) are, among other
things, involved in several non-image-forming visual functions, including light
entrainment of circadian rhythms. Considering the profound impact of aging on
visual function and ophthalmic diseases, here we evaluate changes in mRGCs
throughout the life span in humans. In 24 post-mortem retinas from anonymous
human donors aged 10-81 years, we assessed the distribution, number and
morphology of mRGCs by immunostaining vertical retinal sections and whole-mount
retinas with antibodies against melanopsin. Human retinas showed melanopsin
immunoreactivity in the cell body, axon and dendrites of a subset of ganglion
cells at all ages tested. Nearly half of the mRGCs (51%) were located within the
ganglion cell layer (GCL), and stratified in the outer (M1, 12%) or inner (M2,
16%) margin of the inner plexiform layer (IPL) or in both plexuses (M3, 23%). M1
and M2 cells conformed fairly irregular mosaics, while M3 cell distribution was
slightly more regular. The rest of the mRGCs were more regularly arranged in the
inner nuclear layer (INL) and stratified in the outer margin of the IPL (M1d,
49%). The quantity of each cell type decrease after age 70, when the total number
of mRGCs was 31% lower than in donors aged 30-50 years. Moreover, in retinas with
an age greater than 50 years, mRGCs evidenced a decrease in the dendritic area
that was both progressive and age-dependent, as well as fewer branch points and
terminal neurite tips per cell and a smaller Sholl area. After 70 years of age,
the distribution profile of the mRGCs was closer to a random pattern than was
observed in younger retinas. We conclude that advanced age is associated with a
loss in density and dendritic arborization of the mRGCs in human retinas,
possibly accounting for the more frequent occurrence of circadian rhythm
disorders in elderly persons.
PMID- 28420981
TI - Age-Related Difference in Functional Brain Connectivity of Mastication.
AB - The age-related decline in motor function is associated with changes in intrinsic
brain signatures. Here, we investigated the functional connectivity (FC)
associated with masticatory performance, a clinical index evaluating general
masticatory function. Twenty-six older adults (OA) and 26 younger (YA) healthy
adults were recruited and assessed using the masticatory performance index (MPI)
and resting-state functional magnetic resonance imaging (rs-fMRI). We analyzed
the rs-fMRI FC network related to mastication, which was constructed based on 12
bilateral mastication-related brain regions according to the literature. For the
OA and the YA group, we identified the mastication-related hubs, i.e., the nodes
for which the degree centrality (DC) was positively correlated with the MPI. For
each pair of nodes, we identified the inter-nodal link for which the FC was
positively correlated with the MPI. The network analysis revealed that, in the YA
group, the FC between the sensorimotor cortex, the thalamus (THA) and the
cerebellum was positively correlated with the MPI. Consistently, the cerebellum
nodes were defined as the mastication-related hubs. In contrast, in the OA group,
we found a sparser connection within the sensorimotor regions and cerebellum and
a denser connection across distributed regions, including the FC between the
superior parietal lobe (SPL), the anterior insula (aINS) and the dorsal anterior
cingulate cortex (dACC). Compared to the YA group, the network of the OA group
also comprised more mastication-related hubs, which were spatially distributed
outside the sensorimotor regions, including the right SPL, the right aINS, and
the bilateral dACC. In general, the findings supported the hypothesis that in OA,
higher masticatory performance is associated with a widespread pattern of
mastication-related hubs. Such a widespread engagement of multiple brain regions
associated with the MPI may reflect an increased demand in sensorimotor
integration, attentional control and monitoring for OA to maintain good
mastication.
PMID- 28420982
TI - Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage.
AB - Aging has long been considered as the main risk factor for several
neurodegenerative disorders including a large group of diseases known as
tauopathies. Even though neurofibrillary tangles (NFTs) have been examined as the
main histopathological hallmark, they do not seem to play a role as the toxic
entities leading to disease. Recent studies suggest that an intermediate form of
tau, prior to NFT formation, the tau oligomer, is the true toxic species.
However, the mechanisms by which tau oligomers trigger neurodegeneration remain
unknown. This review summarizes recent findings regarding the role of tau
oligomers in disease, including release from cells, propagation from affected to
unaffected brain regions, uptake into cells, and toxicity via mitochondrial
dysfunction. A greater understanding of tauopathies may lead to future
advancements in regards to prevention and treatment.
PMID- 28420983
TI - Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects
with Parkinson's Disease-Associated LRRK2 Gene Mutations.
AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent
cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2
mutation, G2019S, induces increased production of reactive oxygen species in
vitro. We therefore hypothesized that individuals with PD-associated LRRK2
mutations might have increased concentrations of oxidative stress markers and/or
decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We
measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8
OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD
patients (LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control
subjects with or without these mutations (LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8
ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between
groups. 8-ISO was negatively correlated, and TAC was positively correlated, with
Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects.
Correlations in both groups of PD patients between the two oxidative stress
markers and Unified Parkinson Disease Rating Scale Total scores were weak, while
TAC was negatively correlated with these scores. These findings suggest that
oxidative stress may be increased in the CNS in healthy individuals with PD
associated LRRK2 mutations. Further, TAC may decrease in the CNS with the
progression of PD, and when cognitive impairment is present regardless of the
presence or absence of PD.
PMID- 28420984
TI - Potential Roles of Serum Caveolin-3 Levels in Patients with Atrial Fibrillation.
AB - Objective: To explore serum caveolin-3 (Cav-3) levels in patients with atrial
fibrillation (AF) and to evaluate the role of Cav-3 as a biomarker for AF and
incident heart failure (HF). Methods: Three hundred and five patients were
enrolled in the study and divided into three groups: sinus rhythm (Group SR),
paroxysmal AF (Group paAF), and persistent AF (Group peAF). Serum Cav-3
concentrations were measured by enzyme-linked immunosorbent assay at baseline.
Clinical characteristics, and laboratory data were collected during
hospitalization, and a follow-up of 12-months was carried out. Results: Serum Cav
3 concentrations were significantly decreased on the Group SR and the highest
concentrations of Cav-3 in patients were found on the Group peAF (516.7 +/- 274.0
vs. 609.3 +/- 287.0 vs. 688.3 +/- 264.6 ng/L, P < 0.05). Left atrial diameter
(LAD) in the Group peAF was significantly higher than in the Group paAF, and the
Group SR had significantly lower LAD than the Group paAF and Group peAF. The
risks of new-onset HF in the Group SR, Group paAF, and Group peAF were 8.1, 14.5,
and 28.6%, respectively. There was a significant difference between the Group
peAF and the other two groups. Serum Cav-3 concentrations were trisected in AF
participants (lower tertile: <=498, middle tertile: >498-703, upper tertile:
>=703). In further tertile studies, subjects in the lower tertile of Cav-3
concentrations were more likely to become paroxysmal AF and had much lower LAD (P
< 0.05). And in the middle and upper tertiles, participants with AF tended to
suffer from HF compared to the lower group (P < 0.05). Conclusion: We provide
evidence that Cav-3 has a significant meaning in AF patients. The levels of Cav-3
may be related to the LAD and new-onset HF.
PMID- 28420985
TI - Mapping Dorsal and Ventral Caudate in Older Adults: Method and Validation.
AB - The caudate nucleus plays important roles in cognition and affect. Depending on
associated connectivity and function, the caudate can be further divided into
dorsal and ventral aspects. Dorsal caudate, highly connected to dorsolateral
prefrontal cortex (DLPFC), is implicated in executive function and working
memory; ventral caudate, more interconnected with the limbic system, is
implicated in affective functions such as pain processing. Clinically, certain
brain disorders are known to differentially impact dorsal and ventral caudate.
Thus, precise parcellation of caudate has both basic and clinical neuroscience
significance. In young adults, past work has combined resting-state fMRI
functional connectivity with clustering algorithms to define dorsal and ventral
caudate. Whether the same approach is effective in older adults and how to
validate the parcellation results have not been considered. We addressed these
problems by obtaining resting-state fMRI data from 56 older non-demented adults
(age: 69.07 +/- 5.92 years and MOCA: 25.71 +/- 2.46) along with a battery of
cognitive and clinical assessments. Connectivity from each voxel of caudate to
the rest of the brain was computed using cross correlation. Applying the K-means
clustering algorithm to the connectivity patterns with K = 2 yielded two
substructures within caudate, which agree well with previously reported dorsal
and ventral divisions of caudate. Furthermore, dorsal-caudate-seeded functional
connectivity was shown to be more strongly associated with working memory and
fluid reasoning composite scores, whereas ventral-caudate-seeded functional
connectivity more strongly associated with pain and fatigue severity. These
results demonstrate that dorsal and ventral caudate can be reliably identified by
combining resting-state fMRI and clustering algorithms in older adults.
PMID- 28420986
TI - Modulation of Microglial Activity by Rho-Kinase (ROCK) Inhibition as Therapeutic
Strategy in Parkinson's Disease and Amyotrophic Lateral Sclerosis.
AB - Neurodegenerative diseases are characterized by the progressive degeneration of
neurons in the central and peripheral nervous system (CNS, PNS), resulting in a
reduced innervation of target structures and a loss of function. A shared
characteristic of many neurodegenerative diseases is the infiltration of
microglial cells into affected brain regions. During early disease stages
microglial cells often display a rather neuroprotective phenotype, but switch to
a more pro-inflammatory neurotoxic phenotype in later stages of the disease,
contributing to the neurodegeneration. Activation of the Rho kinase (ROCK)
pathway appears to be instrumental for the modulation of the microglial
phenotype: increased ROCK activity in microglia mediates mechanisms of the
inflammatory response and is associated with improved motility, increased
production of reactive oxygen species (ROS) and release of inflammatory
cytokines. Recently, several studies suggested inhibition of ROCK signaling as a
promising treatment option for neurodegenerative diseases. In this review
article, we discuss the contribution of microglial activity and phenotype switch
to the pathophysiology of Parkinson's disease (PD) and Amyotrophic lateral
sclerosis (ALS), two devastating neurodegenerative diseases without disease
modifying treatment options. Furthermore, we describe how ROCK inhibition can
influence the microglial phenotype in disease models and explore ROCK inhibition
as a future treatment option for PD and ALS.
PMID- 28420987
TI - Curcumin Ameliorates Cisplatin-Induced Nephrotoxicity and Potentiates Its
Anticancer Activity in SD Rats: Potential Role of Curcumin in Breast Cancer
Chemotherapy.
AB - Breast malignant neoplastic disease is one of the most complex diseases, as it is
a multifactorial disease in which virtually all the targets are instantly or
indirectly inter-reliant on each other. Cisplatin (CIS), an inorganic
antineoplastic agent is widely utilized in the treatment of various solid tumors
including breast cancer. Despite everything, its clinical use is limited, due to
ototoxicity, peripheral neuropathy, and nephrotoxicity. The present work was
directed to assess the combined result of curcumin (CUR) and CIS in 7, 12
dimethyl benz[a]anthracene (DMBA) induced breast cancer in rats and the
prevention of nephrotoxicity induced by the latter. CIS-induced nephrotoxicity
was assessed by change in body weight, kidney weight, altered levels of BUN,
creatinine, TNF-alpha, IL-6, IL-8, IL-10, and histopathology of the kidney.
Anticancer activity was assessed by measurement of tumor weight, tumor volume, %
tumor inhibition, levels of PPAR-gamma, and BDNF in mammary tumors and
histopathology of mammary tumors. CUR pre-treatment mitigated nephrotoxicity by
reducing the inflammatory markers (TNF-alpha, IL-6, and IL-8; p < 0.001).
Further, it reduced mammary cancer via increasing the expression of PPAR-gamma (p
< 0.001) and decreasing the expression of BDNF (p < 0.001) in mammary tumors. It
also reduced tumor volume, further postulating that CUR might adjunct the
anticancer activity of the CIS. To the best of our knowledge, this is the first
report, which showed that CUR ameliorated CIS-induced nephrotoxicity and improved
its anticancer activity in DMBA induced breast cancer in female Sprague-Dawley
rats.
PMID- 28420989
TI - FDA Facilitated Regulatory Pathways: Visualizing Their Characteristics,
Development, and Authorization Timelines.
AB - The US Food and Drug Administration (FDA) has four facilitated regulatory
pathways (FRPs): Fast Track (FT), Breakthrough Therapy (BTD), Priority Review
(PR), and Accelerated Approval (AA). Only PR specifies an expedited review
timeline (6 months). We sought to determine to what extent the combination of two
or more FRPs influenced development and approval times. We developed a "metro
map" to illustrate FRP elements and their influence on review times. We assessed
125 new active substances (approved January 2013 to December 2015) 74 of which
used one or more FRPs. For these 74, development times ranged from 1,458 (BTD +
PR + AA) to 3,515 days (PR). PR alone had a median approval time of 242 days. The
most common combination was FT + PR (median approval 292 days, n = 21). The
fastest approval times were for PR + FT + BTD + AA (145 days) and PR + BTD + AA
(166 days). Our findings support the combination of FRPs for shortening
development and review times beyond that provided by PR alone.
PMID- 28420990
TI - Managed Entry Agreements for Oncology Drugs: Lessons from the European Experience
to Inform the Future.
AB - Objectives: The aim of this study is to conduct an analysis on the regulation and
application of managed entry agreements (MEA) for oncology drugs across different
European countries. Methods: Literature search and document analysis were
performed between September 2015 and June 2016 to collect information on the
regulatory framework and practice of MEA in Belgium, The Netherlands, Scotland,
England and Wales, Sweden, Italy, Czech Republic and France. An overview of the
content and typology of MEA applied for oncology drugs between 2008 and 2015 was
generated based on publically available sources and contributions by national
health authorities. Semi-structured interviews were conducted with
representatives of national health authorities involved in the management or
negotiation of MEA. Results: The application of MEA differs across countries and
across different indications for the same drug. Financial based agreements are
prevailing due to their simplicity compared to performance-based agreements.
Performance-based agreements are less commonly applied in the European countries
except for Italy. In the Netherlands, application of performance-based agreements
was stopped due to their inability to deal with dynamics in the market, which is
highly relevant for oncology drugs. Conclusions: MEA constitute a common policy
tool that public payers in European countries use to ensure early access to
highly priced oncology drugs. In light of strengths and weaknesses observed for
MEA and the expected developments in the oncology area, the importance of MEA is
likely to grow in the future.
PMID- 28420991
TI - Gabapentin Attenuates Ocular Inflammation: In vitro and In vivo Studies.
AB - To investigate the effects of gabapentin, a structural analog of gamma-amino
butyric acid (GABA), on the inflammatory response of lipopolysaccharide (LPS)
stimulated rabbit corneal cells (SIRC) and on endotoxin-induced uveitis (EIU) in
rabbits. We investigated the LPS-induced expression of several inflammatory
mediators, such as TNF-alpha, IL-1beta, cPLA2, COX-2, and PGE2 in the SIRC cells
with or without gabapentin treatment. Gabapentin treatment significantly (p <
0.05) attenuated cytokines production, cPLA2 activation, COX-2 expression, and
PGE2 levels in SIRC. EIU was induced by an intraocular injection of 0.1 MUg of
LPS in albino rabbit eye. After 7 and 24 h from LPS injection clinical signs of
ocular inflammation were examined by slit lamp with or without topical treatment
of 0.5% gabapentin. Tears, aqueous, cornea, conjunctiva, and iris-ciliary body
were collected and inflammatory biomarkers assessed. Topical treatment with
gabapentin significantly (p < 0.05) reduced clinical signs and biomarkers of
inflammation compared with the LPS group both at 7 and 24 h. In conclusion, the
results generated in the present study suggest that ophthalmic formulation based
on gabapentin may be useful in the treatment of inflammatory conditions
associated to ocular pain such as uveitis, and that clinical studies to evaluate
this possibility may be warranted.
PMID- 28420988
TI - Heme as a Target for Therapeutic Interventions.
AB - Heme is a complex of iron and the tetrapyrrole protoporphyrin IX with essential
functions in aerobic organisms. Heme is the prosthetic group of hemoproteins such
as hemoglobin and myoglobin, which are crucial for reversible oxygen binding and
transport. By contrast, high levels of free heme, which may occur in various
pathophysiological conditions, are toxic via pro-oxidant, pro-inflammatory and
cytotoxic effects. The toxicity of heme plays a major role for the pathogenesis
of prototypical hemolytic disorders including sickle cell disease and malaria.
Moreover, there is increasing appreciation that detrimental effects of heme may
also be critically involved in diseases, which usually are not associated with
hemolysis such as severe sepsis and atherosclerosis. In mammalians homeostasis of
heme and its potential toxicity are primarily controlled by two physiological
systems. First, the scavenger protein hemopexin (Hx) non-covalently binds
extracellular free heme with high affinity and attenuates toxicity of heme in
plasma. Second, heme oxygenases (HOs), in particular the inducible HO isozyme, HO
1, can provide antioxidant cytoprotection via enzymatic degradation of
intracellular heme. This review summarizes current knowledge on the
pathophysiological role of heme for various diseases as demonstrated in
experimental animal models and in humans. The functional significance of Hx and
HOs for the regulation of heme homeostasis is highlighted. Finally, the
therapeutic potential of pharmacological strategies that apply Hx and HO-1 in
various clinical settings is discussed.
PMID- 28420992
TI - Deficient Adipogenesis of Scleroderma Patient and Healthy African American
Monocytes.
AB - Monocytes from systemic sclerosis (SSc, scleroderma) patients and healthy African
Americans (AA) are deficient in the regulatory protein caveolin-1 leading to
enhanced migration toward chemokines and fibrogenic differentiation. While dermal
fibrosis is the hallmark of SSc, loss of subcutaneous adipose tissue is a lesser
known feature. To better understand the etiology of SSc and the predisposition of
AA to SSc, we studied the adipogenic potential of SSc and healthy AA monocytes.
The ability of SSc and healthy AA monocytes to differentiate into adipocyte-like
cells (ALC) is inhibited compared to healthy Caucasian (C) monocytes. We
validated that monocyte-derived ALCs are distinct from macrophages by flow
cytometry and immunocytochemistry. Like their enhanced fibrogenic
differentiation, their inhibited adipogenic differentiation is reversed by the
caveolin-1 scaffolding domain peptide (CSD, a surrogate for caveolin-1). The
altered differentiation of SSc and healthy AA monocytes is additionally regulated
by peroxisome proliferator-activated receptor gamma (PPARgamma) which is also
present at reduced levels in these cells. In vivo studies further support the
importance of caveolin-1 and PPARgamma in fibrogenesis and adipogenesis. In SSc
patients, healthy AA, and mice treated systemically with bleomycin, adipocytes
lose caveolin-1 and PPARgamma and the subcutaneous adipose layer is diminished.
CSD treatment of these mice leads to a reappearance of the caveolin
1+/PPARgamma+/FABP4+ subcutaneous adipose layer. Moreover, many of these
adipocytes are CD45+, suggesting they are monocyte derived. Tracing experiments
with injected EGFP+ monocytes confirm that monocytes contribute to the repair of
the adipose layer when it is damaged by bleomycin treatment. Our observations
strongly suggest that caveolin-1 and PPARgamma work together to maintain a
balance between the fibrogenic and adipogenic differentiation of monocytes, that
this balance is altered in SSc and in healthy AA, and that monocytes make a major
contribution to the repair of the adipose layer.
PMID- 28420993
TI - Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury
through Autophagic Regulation.
AB - The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly
increasing around the world and this disease is a major contributor to global
morbidity and mortality. It is known that regulation of programmed cell death
including apoptosis and autophagy reduces the impact of myocardial IR injury. In
this study, the cardioprotective effects and underlying mechanisms of Phellinus
linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal
mushroom, were examined in rats subjected to myocardial IR injury. The left main
coronary artery of rats was ligated for 1 h and reperfused for 3 h. The
arrhythmia levels were monitored during the entire process and the infarct size
was evaluated after myocardial IR injury. Furthermore, the expression levels of
proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL
mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to
myocardial IR injury. PLM also significantly decreased myocardial infarct size
and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM
administration resulted in decreased caspase 3 and caspase 9 activation and
increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR
level was reduced. Becline-1 and p62 levels decreased. These findings suggest
that PLM is effective in protecting the myocardium against IR injury. The
mechanism involves mediation through suppressed pro-apoptotic signaling and
regulation of autophagic signaling, including stimulation of AMPK-dependent
pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of
protective autophagy and inhibition of excessive autophagy.
PMID- 28420994
TI - Scaffold Diversity of Fungal Metabolites.
AB - Many drug discovery projects rely on commercial compounds to discover active
leads. However, current commercial libraries, with mostly synthetic compounds,
access a small fraction of the possible chemical diversity. Natural products, in
contrast, possess a vast structural diversity and have proven to be an
outstanding source of new drugs. Several chemoinformatic analyses of natural
products have demonstrated their diversity and structural complexity. However, to
our knowledge, the scaffold content and structural diversity of fungal secondary
metabolites have never been studied. Herein, the scaffold diversity of 223 fungal
metabolites was measured and compared to the diversity of approved drugs and
commercial libraries for HTS containing natural, synthetic, and semi-synthetic
compounds. In addition, the global diversity of the fungal isolates was assessed
and compared to other reference data sets using Consensus Diversity Plots, a
chemoinformatic tool recently developed. It was concluded that fungal secondary
metabolites are cyclic systems with few ramifications and more diverse than the
commercial libraries with natural products and semi-synthetic compounds. The
fungal metabolites data set was one of the most structurally diverse, containing
a large proportion of different and unique scaffolds not found in the other
compound data sets including ChEMBL. Therefore, fungal metabolites offer a rich
source of molecules suited for identifying diverse candidates for drug discovery.
PMID- 28420995
TI - Quantum Dots-siRNA Nanoplexes for Gene Silencing in Central Nervous System Tumor
Cells.
AB - RNA interfering (RNAi) using short interfering RNA (siRNA) is becoming a
promising approach for cancer gene therapy. However, owing to the lack of safe
and efficient carriers, the application of RNAi for clinical use is still very
limited. In this study, we have developed cadmium sulphoselenide/Zinc sulfide
quantum dots (CdSSe/ZnS QDs)-based nanocarriers for in vitro gene delivery. These
CdSSe/ZnS QDs are functionalized with polyethyleneimine (PEI) to form stable
nanoplex (QD-PEI) and subsequently they are used for siRNA loading which
specially targets human telomerase reverse transcriptase (TERT). High gene
transfection efficiency (>80%) was achieved on two glioblastoma cell lines, U87
and U251. The gene expression level (49.99 +/- 10.23% for U87, 43.28 +/- 9.66%
for U251) and protein expression level (51.58 +/- 7.88% for U87, 50.69 +/- 7.59%
for U251) of TERT is observed to decrease substantially after transfecting the
tumor cells for 48 h. More importantly, the silencing of TERT gene expression
significantly suppressed the proliferation of glioblastoma cells. No obvious
cytotoxicity from these QD-PEI nanoplexes were observed over at 10 times of the
transfected doses. Based on these results, we envision that QDs engineered here
can be used as a safe and efficient gene nanocarrier for siRNA delivery and a
promising tool for future cancer gene therapy applications.
PMID- 28420996
TI - Chronic Water-Pipe Smoke Exposure Induces Injurious Effects to Reproductive
System in Male Mice.
AB - There is a global increase in the popularity of water-pipe tobacco smoking
including in Europe and North America. Nevertheless, little is known about the
male reproductive effects of water-pipe smoke (WPS), especially after long-term
exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for
6 months. Control mice were exposed to air-only for the same period of time.
Twenty-four hours after the last exposure, testicular histopathology, and markers
of inflammation and oxidative stress, and the tyrosine-protein kinase vascular
endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular
homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone
(LH) concentrations were also measured. Chronic WPS exposure induced a
significant decrease of testosterone and estradiol, and a slight but significant
increase of LH. Glutathione reductase, catalase, and ascorbic acid were
significantly decreased following WPS exposure. Plasma concentration of leptin
was significantly decreased by WPS exposure, whereas that of tumor necrosis
factor alpha and interleukin 6 was significantly increased. Histopathological
analysis of the testes revealed the presence of a marked reduction in the
diameter of the seminiferous tubules with reduced spermatogenesis. Transmission
electron microscopy examination showed irregular thickening and wrinkling of the
basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1
was overexpressed in the testis of the mice exposed to WPS and was not detected
in the control. The urine concentration of cotinine, the predominant metabolite
of nicotine, was significantly increased in the WPS-exposed group compared with
the control group. We conclude that chronic exposure to WPS induces damaging
effects to the reproductive system in male mice. If this can be confirmed in
humans, it would be an additional concern to an already serious public health
problem, especially with the increased use of WPS use all over the world,
especially in young adults.
PMID- 28420998
TI - Instant Biofeedback Provided by Wearable Sensor Technology Can Help to Optimize
Exercise and Prevent Injury and Overuse.
PMID- 28420997
TI - MicroRNAs in Palatogenesis and Cleft Palate.
AB - Palatogenesis requires a precise spatiotemporal regulation of gene expression,
which is controlled by an intricate network of transcription factors and their
corresponding DNA motifs. Even minor perturbations of this network may cause
cleft palate, the most common congenital craniofacial defect in humans. MicroRNAs
(miRNAs), a class of small regulatory non-coding RNAs, have elicited strong
interest as key regulators of embryological development, and as etiological
factors in disease. MiRNAs function as post-transcriptional repressors of gene
expression and are therefore able to fine-tune gene regulatory networks. Several
miRNAs are already identified to be involved in congenital diseases. Recent
evidence from research in zebrafish and mice indicates that miRNAs are key
factors in both normal palatogenesis and cleft palate formation. Here, we provide
an overview of recently identified molecular mechanisms underlying palatogenesis
involving specific miRNAs, and discuss how dysregulation of these miRNAs may
result in cleft palate.
PMID- 28420999
TI - Functional High-Intensity Circuit Training Improves Body Composition, Peak Oxygen
Uptake, Strength, and Alters Certain Dimensions of Quality of Life in Overweight
Women.
AB - The effects of circuit-like functional high-intensity training (CircuitHIIT)
alone or in combination with high-volume low-intensity exercise (Circuitcombined)
on selected cardio-respiratory and metabolic parameters, body composition,
functional strength and the quality of life of overweight women were compared. In
this single-center, two-armed randomized, controlled study, overweight women
performed 9-weeks (3 sessions.wk-1) of either CircuitHIIT (n = 11), or
Circuitcombined (n = 8). Peak oxygen uptake and perception of physical pain were
increased to a greater extent (p < 0.05) by CircuitHIIT, whereas Circuitcombined
improved perception of general health more (p < 0.05). Both interventions lowered
body mass, body-mass-index, waist-to-hip ratio, fat mass, and enhanced fat-free
mass; decreased ratings of perceived exertion during submaximal treadmill
running; improved the numbers of push-ups, burpees, one-legged squats, and 30-s
skipping performed, as well as the height of counter-movement jumps; and improved
physical and social functioning, role of physical limitations, vitality, role of
emotional limitations, and mental health to a similar extent (all p < 0.05).
Either forms of these multi-stimulating, circuit-like, multiple-joint training
can be employed to improve body composition, selected variables of functional
strength, and certain dimensions of quality of life in overweight women. However,
CircuitHIIT improves peak oxygen uptake to a greater extent, but with more
perception of pain, whereas Circuitcombined results in better perception of
general health.
PMID- 28421000
TI - Photodynamic Physiology-Photonanomanipulations in Cellular Physiology with
Protein Photosensitizers.
AB - Singlet oxygen generated in a type II photodynamic action, due to its limited
lifetime (1 MUs) and reactive distance (<10 nm), could regulate live cell
function nanoscopically. The genetically-encoded protein photosensitizers
(engineered fluorescent proteins such as KillerRed, TagRFP, and flavin-binding
proteins such as miniSOG, Pp2FbFPL30M) could be expressed in a cell type- and/or
subcellular organelle-specific manner for targeted protein photo-oxidative
activation/desensitization. The newly emerged active illumination technique
provides an additional level of specificity. Typical examples of photodynamic
activation include permanent activation of G protein-coupled receptor CCK1 and
photodynamic activation of ionic channel TRPA1. Protein photosensitizers have
been used to photodynamically modulate major cellular functions (such as
neurotransmitter release and gene transcription) and animal behavior. Protein
photosensitizers are increasingly used in photon-driven nanomanipulation in cell
physiology research.
PMID- 28421001
TI - Defining the Balance between Regeneration and Pathological Ossification in
Skeletal Muscle Following Traumatic Injury.
AB - Heterotopic ossification (HO) is characterized by the formation of bone at
atypical sites. This type of ectopic bone formation is most prominent in skeletal
muscle, most frequently resulting as a consequence of physical trauma and
associated with aberrant tissue regeneration. The condition is debilitating,
reducing a patient's range of motion and potentially causing severe pathologies
resulting from nerve and vascular compression. Despite efforts to understand the
pathological processes governing HO, there remains a lack of consensus regarding
the micro-environmental conditions conducive to its formation, and attempting to
define the balance between muscle regeneration and pathological ossification
remains complex. The development of HO is thought to be related to a complex
interplay between factors released both locally and systemically in response to
trauma. It develops as skeletal muscle undergoes significant repair and
regeneration, and is likely to result from the misdirected differentiation of
endogenous or systemically derived progenitors in response to biochemical and/or
environmental cues. The process can be sequentially delineated by the presence of
inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis,
chondrogenesis and ossification. However, exactly how each of these stages
contributes to the formation of HO is at present not well understood. Our
previous review examined the cellular contribution to HO. Therefore, the
principal aim of this review will be to comprehensively outline changes in the
local tissue micro-environment following trauma, and identify how these changes
can alter the balance between skeletal muscle regeneration and ectopic
ossification. An understanding of the mechanisms governing this condition is
required for the development and advancement of HO prophylaxis and treatment, and
may even hold the key to unlocking novel methods for engineering hard tissues.
PMID- 28421003
TI - Acellular Gelatinous Material of Human Umbilical Cord Enhances Wound Healing: A
Candidate Remedy for Deficient Wound Healing.
AB - Impaired wound healing is a severe clinical challenge and research into finding
effective wound healing strategies is underway as there is no ideal treatment.
Gelatinous material from the umbilical cord called Wharton's jelly is a valuable
source of mesenchymal stem cells which have been shown to aid wound healing.
While the cellular component of Wharton's jelly has been the subject of extensive
research during the last few years, little is known about the de-cellularized
jelly material of the umbilical cord. This is important as they are native niche
of stem cells. We have isolated Wharton's jelly from umbilical cords and then
fractionated acellular gelatinous Wharton's jelly (AGWJ). Here, we show for the
first time that AGWJ enhances wound healing in vitro as well as in vivo for
wounds in a murine model. In vivo staining of the wounds revealed a smaller wound
length in the AGWJ treated wounds in comparison to control treatment by enhancing
cell migration and differentiation. AGWJ significantly enhanced fibroblast cell
migration in vitro. Aside from cell migration, AGWJ changed the cell morphology
of fibroblasts to a more elongated phenotype, characteristic of myofibroblasts,
confirmed by upregulation of alpha smooth muscle actin using immunoblotting. AGWJ
treatment of wounds led to accelerated differentiation of cells into
myofibroblasts, shortening the proliferation phase of wound healing. This data
provides support for a novel wound healing remedy using AGWJ. AGWJ being native
biological, cost effective and abundantly available globally, makes it a highly
promising treatment option for wound dressing and skin regeneration.
PMID- 28421002
TI - Application of Stem Cells in Oral Disease Therapy: Progresses and Perspectives.
AB - Stem cells are undifferentiated and pluripotent cells that can differentiate into
specialized cells with a more specific function. Stem cell therapies become
preferred methods for the treatment of multiple diseases. Oral and maxillofacial
defect is one kind of the diseases that could be most possibly cured by stem cell
therapies. Here we discussed oral diseases, oral adult stem cells, iPS cells, and
the progresses/challenges/perspectives of application of stem cells for oral
disease treatment.
PMID- 28421004
TI - Neurosensory and Cognitive Modifications in Europe's Toughest RandoRaid
Competition: the Transpyrenea Extreme Study.
AB - Introduction: Given the wide proliferation of ultra-long endurance races, it is
important to understand the physiological response of the athletes to improve
their safety. We evaluated the cognitive and neurosensory effects on ultra
endurance athletes during the Transpyrenea (866 Km, 65,000 m positive slope),
held on the French Pyrenees. Materials and Methods: 40 athletes were enrolled
(age 43.8 +/- 8.8 years; 36 males). Olfactory and cognitive tests were performed
before the race (T0, n = 40), at 166 kms (T1, n = 28), at 418 kms (T2, n = 20),
and after the race (T3, 866 kms, n = 13). The effect of dehydration and sleep
deprivation on cognitive features were also studied. Results: Olfactory function
decreased during the race (T0: 24.9 +/- 4.3 vs. T3: 22.8 +/- 3.5, z = -2.678, p =
0.007), language fluency increased (T0: 10.8 +/- 2.9; T1: 11.4 +/- 2.7; T2: 12.9
+/- 2.8; T3: 12.9 +/- 3.0; chi2 = 11.132, p = 0.011 for combined samples),
whereas the Trail Making Test did not show any changes between pre- and post-race
(T0 vs. T3 p = 0.697 for TMT-A, p = 0.977 for TMT-B). The mean aggregate sleeping
time was 9.3 +/- 5.4 h at T1, 22.4 +/- 10.0 h at T2, 29.5 +/- 20.5 h at T3, with
a correlation with olfactory function (r = 0.644, p = 0.018), while Total Body
Water (TBW) was not correlated with olfactory or cognitive scores. Conclusion:
Physical activity and sleep restriction in ultra-endurance could transiently
affect olfactory function, while verbal fluency improved, demonstrating a
dissimilar mechanism of activation/deactivation in different cortical areas. Body
water loss was uncorrelated to cognition. Further studies should clarify whether
cognitive and sensory deficits occur even in absence of sleep restriction.
PMID- 28421006
TI - Do Demographic Characteristics Make Differences? Demographic Characteristics as
Moderators in the Associations between Only Child Status and Cognitive/Non
cognitive Outcomes in China.
AB - Different family compositions and sizes may affect child development through the
different modes of interaction between family members. Previous studies have
compared only children with non-only children in cognitive/non-cognitive
outcomes. However, relatively little research has systematically investigated the
potential moderators among them. Using a large and representative sample of
Chinese students (Grades 7-8; N = 5,752), this study examines the roles of
demographic characteristics, such as gender, region, parental educational level,
parental expectations, family socio-economic status and family structure, in the
associations between only child status and cognitive/non-cognitive outcomes. For
the cognitive outcomes, only child status exerts an influence on the students'
academic performance in Chinese and mathematics in the sample of three districts'
students. The examined associations between only child status and cognitive
outcomes are different in region, parental education, parental expectations and
family structure, while gender and family socio-economic status did not. For the
non-cognitive outcomes, only child status exerts an influence on the students'
school well-being, academic self-efficacy, academic self-concept, and internal
academic motivation in the full sample of students, but not on external academic
motivation. Further, the examined associations between only child status and non
cognitive outcomes are different in region, parental education, family socio
economic status and family structure, while gender and parental expectations did
not. These findings suggest that the associations between only child status and
cognitive/non-cognitive outcomes are heterogeneous in terms of some of the
demographic characteristics. Possible explanations are proposed in some concepts
of region and family environment in China.
PMID- 28421007
TI - Arousal Rules: An Empirical Investigation into the Aesthetic Experience of Cross
Modal Perception with Emotional Visual Music.
AB - Emotional visual music is a promising tool for the study of aesthetic perception
in human psychology; however, the production of such stimuli and the mechanisms
of auditory-visual emotion perception remain poorly understood. In Experiment 1,
we suggested a literature-based, directive approach to emotional visual music
design, and inspected the emotional meanings thereof using the self-rated
psychometric and electroencephalographic (EEG) responses of the viewers. A two
dimensional (2D) approach to the assessment of emotion (the valence-arousal
plane) with frontal alpha power asymmetry EEG (as a proposed index of valence)
validated our visual music as an emotional stimulus. In Experiment 2, we used our
synthetic stimuli to investigate possible underlying mechanisms of affective
evaluation mechanisms in relation to audio and visual integration conditions
between modalities (namely congruent, complementation, or incongruent
combinations). In this experiment, we found that, when arousal information
between auditory and visual modalities was contradictory [for example, active (+)
on the audio channel but passive (-) on the video channel], the perceived emotion
of cross-modal perception (visual music) followed the channel conveying the
stronger arousal. Moreover, we found that an enhancement effect (heightened and
compacted in subjects' emotional responses) in the aesthetic perception of visual
music might occur when the two channels contained contradictory arousal
information and positive congruency in valence and texture/control. To the best
of our knowledge, this work is the first to propose a literature-based directive
production of emotional visual music prototypes and the validations thereof for
the study of cross-modally evoked aesthetic experiences in human subjects.
PMID- 28421008
TI - Understanding Rejection between First-and-Second-Grade Elementary Students
through Reasons Expressed by Rejecters.
AB - Objective: The aim of this research was to obtain the views of young children
regarding their reasons for rejecting a peer. Method: To achieve this goal, we
conducted a qualitative study in the context of theory building research using an
analysis methodology based on Grounded Theory. The collected information was
extracted through semi-structured individual interviews from a sample of 853
children aged 6 from 13 urban public schools in Spain. Results: The children
provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected
peers. Seven reason categories emerged from the analysis. Four categories refer
to behaviors of the rejected children that have a cost for individual peers or
peer group such as: direct aggression, disturbance of wellbeing, problematic
social and school behaviors and dominance behaviors. A further two categories
refer to the identities arising from the preferences and choices of rejected and
rejecter children and their peers: personal identity expressed through
preferences and disliking, and social identity expressed through outgroup
prejudices. The "no-behavior or no-choice" reasons were covered by one category,
unfamiliarity. In addition, three context categories were found indicating the
participants (interpersonal-group), the impact (low-high), and the subjectivity
(subjective-objective) of the reason. Conclusion: This study provides researchers
and practitioners with a comprehensive taxonomy of reasons for rejection that
contributes to enrich the theoretical knowledge and improve interventions for
preventing and reducing peer rejection.
PMID- 28421005
TI - Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases: A Template for
Innovative Therapy.
AB - Neurodegenerative and psychiatric diseases (NPDs) are today's most important
group of diseases, surpassing both atherosclerotic cardiovascular disease and
cancer in morbidity incidence. Although NPDs have a dramatic impact on our
society because of their high incidence, mortality, and severe debilitating
character, remarkably few effective interventions have become available. The
current treatments, if available, comprise the lifelong intake of general
immunosuppressants to delay disease progression or neurotransmitter
antagonists/agonists to dampen undesired behaviors. The long-term usage of such
medication, however, coincides with often severe adverse side effects. There is,
therefore, an urgent need for safe and effective treatments for these diseases.
Here, we discuss that many NPDs coincide with subtle chronic or flaring brain
inflammation sometimes escalating with infiltrations of lymphocytes in the
inflamed brain parts causing mild to severe or even lethal brain damage. Thus,
NPDs show all features of autoimmune diseases. In this review, we postulate that
NPDs resemble autoimmune-driven inflammatory diseases in many aspects and may
belong to the same disease spectrum. Just like in autoimmune diseases, NPD
symptoms basically are manifestations of a chronic self-sustaining inflammatory
process with detrimental consequences for the patient. Specific inhibition of the
destructive immune responses in the brain, leaving the patient's immune system
intact, would be the ultimate solution to cure patients from the disease. To
reach this goal, the primary targets, e.g., the primary self-antigens (pSAgs) of
the patient's chronic (auto)immune response, need to be identified. For a few
major NPDs, immunological studies led to the identification of the pSAgs involved
in the autoimmune damage of specific brain parts. However, further research is
needed to complete the list of pSAgs for all NPDs. Such immunological studies
will not only provide crucial insights into NPD pathogenesis but also ultimately
enable the development of a new generation of safe and effective immunotherapies
for NPDs. Interventions that will dramatically improve the life expectancy and
quality of life of individual patients and, moreover, will significantly reduce
the health-care costs of the society in general.
PMID- 28421011
TI - Practical Consequences of Item Response Theory Model Misfit in the Context of
Test Equating with Mixed-Format Test Data.
AB - In item response theory (IRT) models, assessing model-data fit is an essential
step in IRT calibration. While no general agreement has ever been reached on the
best methods or approaches to use for detecting misfit, perhaps the more
important comment based upon the research findings is that rarely does the
research evaluate IRT misfit by focusing on the practical consequences of misfit.
The study investigated the practical consequences of IRT model misfit in
examining the equating performance and the classification of examinees into
performance categories in a simulation study that mimics a typical large-scale
statewide assessment program with mixed-format test data. The simulation study
was implemented by varying three factors, including choice of IRT model, amount
of growth/change of examinees' abilities between two adjacent administration
years, and choice of IRT scaling methods. Findings indicated that the extent of
significant consequences of model misfit varied over the choice of model and IRT
scaling methods. In comparison with mean/sigma (MS) and Stocking and Lord
characteristic curve (SL) methods, separate calibration with linking and fixed
common item parameter (FCIP) procedure was more sensitive to model misfit and
more robust against various amounts of ability shifts between two adjacent
administrations regardless of model fit. SL was generally the least sensitive to
model misfit in recovering equating conversion and MS was the least robust
against ability shifts in recovering the equating conversion when a substantial
degree of misfit was present. The key messages from the study are that practical
ways are available to study model fit, and, model fit or misfit can have
consequences that should be considered when choosing an IRT model. Not only does
the study address the consequences of IRT model misfit, but also it is our hope
to help researchers and practitioners find practical ways to study model fit and
to investigate the validity of particular IRT models for achieving a specified
purpose, to assure that the successful use of the IRT models are realized, and to
improve the applications of IRT models with educational and psychological test
data.
PMID- 28421010
TI - Teacher Evaluations of Executive Functioning in Schoolchildren Aged 9-12 and the
Influence of Age, Sex, Level of Parental Education.
AB - Executive functions (EFs) develop over the period of early childhood and
adolescence up until young adulthood. Individual children differ substantially in
the pace at which their EFs develop, and characteristics such as sex and the
level of parental education (LPE) are thought to contribute to these differences.
In the present study, we assessed age-related changes in EFs as perceived and
evaluated by teachers and parents as well as the influence of sex and LPE on
their evaluations. We used a newly developed observer-report questionnaire, the
Amsterdam Executive Function Inventory (AEFI). The AEFI assesses three important
components of the executive aspects of daily life behavior in 13 questions:
Attention; Self-control and Self-monitoring; and Planning and Initiative taking.
Teachers and parents evaluated these aspects of executive functioning in 186
schoolchildren in grades 3-6 (age: 9-12 years). Age effects within grades and
differences in social economic status between the four participating schools were
controlled. Results showed a significant increase in teacher-perceived EFs from
third to fourth grades and from fifth to sixth grades. This development was
influenced both by the sex of the child and by the LPE. As perceived by teachers,
the component self-control and self-monitoring was higher for girls than for
boys, and planning abilities were higher for children from families with a higher
LPE. Additional analyses showed that there is a systematic and statistically
significant difference between the evaluations of the teachers and that of
parents. Parents reported higher scores for planning, whereas teachers reported
higher scores for self-control and self-monitoring. Evaluations by parents and
teachers were different for girls, but not for boys. These findings are important
because they imply that the development of EFs as perceived by parents and
teachers is influenced by child-related factors. Second, there are clear
differences in evaluations between teachers and parents. The AEFI appears to be a
tool that is easily used by parents and teachers and shows potential for
monitoring the development of EFs as perceived by significant others during young
adolescence.
PMID- 28421009
TI - Food Addiction in Gambling Disorder: Frequency and Clinical Outcomes.
AB - Background: The food addiction (FA) model is receiving increasing interest from
the scientific community. Available empirical evidence suggests that this
condition may play an important role in the development and course of physical
and mental health conditions such as obesity, eating disorders, and other
addictive behaviors. However, no epidemiological data exist on the comorbidity of
FA and gambling disorder (GD), or on the phenotype for the co-occurrence of
GD+FA. Objectives: To determine the frequency of the comorbid condition GD+FA, to
assess whether this comorbidity features a unique clinical profile compared to GD
without FA, and to generate predictive models for the presence of FA in a GD
sample. Method: Data correspond to N = 458 treatment-seeking patients who met
criteria for GD in a hospital unit specialized in behavioral addictions. Results:
Point prevalence for FA diagnosis was 9.2%. A higher ratio of FA was found in
women (30.5%) compared to men (6.0%). Lower FA prevalence was associated with
older age. Patients with high FA scores were characterized by worse psychological
state, and the risk of a FA diagnosis was increased in patients with high scores
in the personality traits harm avoidance and self-transcendence, and low scores
in cooperativeness (R2 = 0.18). Conclusion: The co-occurrence of FA in treatment
seeking GD patients is related to poorer emotional and psychological states. GD
treatment interventions and related behavioral addictions should consider
potential associations with problematic eating behavior and aim to include
techniques that aid patients in better managing this behavior.
PMID- 28421012
TI - Moderated Online Social Therapy: A Model for Reducing Stress in Carers of Young
People Diagnosed with Mental Health Disorders.
AB - Family members caring for a young person diagnosed with the onset of mental
health problems face heightened stress, depression, and social isolation. Despite
evidence for the effectiveness of family based interventions, sustaining access
to specialist family interventions is a major challenge. The availability of the
Internet provides possibilities to expand and sustain access to evidence-based
psychoeducation and personal support for family members. In this paper we
describe the therapeutic model and the components of our purpose-built moderated
online social therapy (MOST) program for families. We outline the background to
its development, beginning with our face-to-face EPISODE II family intervention,
which informed our selection of therapeutic content, and the integration of
recent developments in positive psychology. Our online interventions for carers
integrate online therapy, online social networking, peer and expert support, and
online social problem solving which has been designed to reduce stress in carers.
The initial version of our application entitled Meridian was shown to be safe,
acceptable, and feasible in a feasibility study of carers of youth diagnosed with
depression and anxiety. There was a significant reduction in self-reported levels
of stress in caregivers and change in stress was significantly correlated with
use of the system. We have subsequently launched a cluster RCT for caregivers
with a relative diagnosed with first-episode psychosis. Our intervention has the
potential to improve access to effective specialist support for families facing
the onset of serious mental health problems in their young relative.
PMID- 28421014
TI - Group Rumination: Social Interactions Around Music in People with Depression.
AB - One of the most important roles that music serves in human society is the
promotion of social relationships and group cohesion. In general, emotional
experiences tend to be amplified in group settings through processes of social
feedback. However, previous research has established that listening to sad music
can intensify negative emotions in people with tendencies to rumination and
depression. This study therefore investigated the phenomenon of ruminating with
music, and the question of whether listening to sad music in group settings
provides social benefits for emotionally vulnerable listeners, or whether it
further exaggerates depressive tendencies. Participants recruited via online
depression groups and mental health websites were surveyed as to music listening
habits. Results revealed that people with depression were more likely to engage
in "group rumination" using music, and that this behavior could be partially
explained by a general tendency to ruminate using music. Both affective states
and coping styles were found to be related to the affective outcomes of group
interactions around music. These findings go some way toward clarifying the
situations in which group interactions around music are able to provide important
social benefits for those involved, and situations in which negative emotions can
be amplified by the group context.
PMID- 28421013
TI - The Blurred Future of Adolescent Gamblers: Impulsivity, Time Horizon, and
Emotional Distress.
AB - The main purpose of this study was to investigate the interplay of functional and
dysfunctional impulsivity, delay discounting, time perspective, and emotional
negative states on gambling severity in Italian adolescents. A second aim of the
study was to analyze the developmental trajectories of gambling involvement,
functional and dysfunctional impulsivity, delay discounting, consideration of
future consequences, and negative affectivity in a cross-sectional perspective.
One thousand and ten Italian adolescents aging between 12 and 19 years were
administered the South Oaks Gambling Screen Revised for Adolescents (SOGS-RA),
the Functional and Dysfunctional Impulsivity Scale (FDIS), the Monetary Choice
Questionnaire (MCQ), the Consideration of Future Consequences Scale (CFC-14), and
the Depression, Anxiety and Stress Scales-21 (DASS-21). Data analyses were
conducted using correlational analysis, Chi-square test, analysis of variance,
and hierarchical regression analysis. Results indicated that, relative to non
gamblers and non-problem gamblers, at-risk and problem gamblers showed higher
levels of impulsivity, steeper delay discounting, shorter time horizon, and
reported experiencing significantly higher levels of depression, anxiety, and
stress. Results of hierarchical regression analysis, with SOGS-RA scores as the
dependent variable, and gender, age, FDIS, MCQ, CFC-14, and DASS-21 scores as
independent variables, indicated that, along with gender and age, low scores of
future orientation and high scores of dysfunctional impulsivity, depression,
anxiety, present orientation, and delay discounting significantly predicted
gambling severity. These findings provide further evidence that the higher the
gambling involvement, the greater the tendency to devalue delayed rewards and to
focus on the immediate consequences of one's behavior. Interestingly, for the
first time these results reveal an association between gambling severity and both
dysfunctional impulsivity and negative affective states across adolescence.
Finally, results of cross-sectional analyses suggest that gambling severity
contributes more than age in shaping the developmental trajectories of functional
and dysfunctional impulsivity, delay discounting, time perspective, and negative
affective states.
PMID- 28421015
TI - Music and Its Inductive Power: A Psychobiological and Evolutionary Approach to
Musical Emotions.
AB - The aim of this contribution is to broaden the concept of musical meaning from an
abstract and emotionally neutral cognitive representation to an emotion
integrating description that is related to the evolutionary approach to music.
Starting from the dispositional machinery for dealing with music as a temporal
and sounding phenomenon, musical emotions are considered as adaptive responses to
be aroused in human beings as the product of neural structures that are
specialized for their processing. A theoretical and empirical background is
provided in order to bring together the findings of music and emotion studies and
the evolutionary approach to musical meaning. The theoretical grounding
elaborates on the transition from referential to affective semantics, the
distinction between expression and induction of emotions, and the tension between
discrete-digital and analog-continuous processing of the sounds. The empirical
background provides evidence from several findings such as infant-directed
speech, referential emotive vocalizations and separation calls in lower mammals,
the distinction between the acoustic and vehicle mode of sound perception, and
the bodily and physiological reactions to the sounds. It is argued, finally, that
early affective processing reflects the way emotions make our bodies feel, which
in turn reflects on the emotions expressed and decoded. As such there is a
dynamic tension between nature and nurture, which is reflected in the nature
nurture-nature cycle of musical sense-making.
PMID- 28421016
TI - Online Coaching of Emotion-Regulation Strategies for Parents: Efficacy of the
Online Rational Positive Parenting Program and Attention Bias Modification
Procedures.
AB - Parenting programs are currently treatment of choice for behavioral disorders in
children and one of their main components is reducing the negativity bias in the
child-parent dyad. The Rational Positive Parenting Program (rPPP) is a program
with a special focus on parent emotion-regulation functional reappraisal
strategies, which has recently received consistent support for reducing child
externalizing and internalizing disorders. In the last years, online
interventions were proliferated and the Attention Bias Modification (ABM)
becoming a promising implicit therapeutic intervention based on attention
deployment emotion-regulation strategy, or adjunctive module to usual treatments,
with results in multiple domains, varying from pain to self-esteem and emotional
disorders (e.g., anxiety). We conducted two studies to investigate (1) the
efficacy of the ABM procedures applied to parents and (2) the efficacy of the
online version of the rPPP augmented with an ABM module. A total of 42 parents of
children aged 2-12 years old participated in the first study, being allocated
either to the ABM training or wait-list. Positive results were reported by the
parents participating in the ABM group for own distress, satisfaction, positive
interactions with the child, and child's strengths. In the second study, 53
parents and their children were allocated either in the rPPP group or in the rPPP
+ ABM group. Results show that ABM training can boost the effects of the rPPP on
the strengths of children reported by the parents after the intervention.
Findings are discussed in the light of limited research on using online tools for
coaching effective emotion-regulation strategies for parents.
PMID- 28421018
TI - The Emergence of Explicit Knowledge in a Serial Reaction Time Task: The Role of
Experienced Fluency and Strength of Representation.
AB - The Serial Reaction Time Task (SRTT) is an important paradigm to study the
properties of unconscious learning processes. One specifically interesting and
still controversially discussed topic are the conditions under which
unconsciously acquired knowledge becomes conscious knowledge. The different
assumptions about the underlying mechanisms can contrastively be separated into
two accounts: single system views in which the strengthening of associative
weights throughout training gradually turns implicit knowledge into explicit
knowledge, and dual system views in which implicit knowledge itself does not
become conscious. Rather, it requires a second process which detects changes in
performance and is able to acquire conscious knowledge. In a series of three
experiments, we manipulated the arrangement of sequential and deviant trials. In
an SRTT training, participants either received mini-blocks of sequential trials
followed by mini-blocks of deviant trials (22 trials each) or they received
sequential and deviant trials mixed randomly. Importantly the number of correct
and deviant transitions was the same for both conditions. Experiment 1 showed
that both conditions acquired a comparable amount of implicit knowledge,
expressed in different test tasks. Experiment 2 further demonstrated that both
conditions differed in their subjectively experienced fluency of the task, with
more fluency experienced when trained with mini-blocks. Lastly, Experiment 3
revealed that the participants trained with longer mini-blocks of sequential and
deviant material developed more explicit knowledge. Results are discussed
regarding their compatibility with different assumptions about the emergence of
explicit knowledge in an implicit learning situation, especially with respect to
the role of metacognitive judgements and more specifically the Unexpected-Event
Hypothesis.
PMID- 28421017
TI - Review on Neural Correlates of Emotion Regulation and Music: Implications for
Emotion Dysregulation.
AB - Previous studies have examined the neural correlates of emotion regulation and
the neural changes that are evoked by music exposure. However, the link between
music and emotion regulation is poorly understood. The objectives of this review
are to (1) synthesize what is known about the neural correlates of emotion
regulation and music-evoked emotions, and (2) consider the possibility of
therapeutic effects of music on emotion dysregulation. Music-evoked emotions can
modulate activities in both cortical and subcortical systems, and across cortical
subcortical networks. Functions within these networks are integral to generation
and regulation of emotions. Since dysfunction in these networks are observed in
numerous psychiatric disorders, a better understanding of neural correlates of
music exposure may lead to more systematic and effective use of music therapy in
emotion dysregulation.
PMID- 28421019
TI - Gender Moderates the Influence of Self-Construal Priming on Fairness
Considerations.
AB - Research in social and cultural psychology has identified that self-construal, or
the way the self is defined in relation to others, plays an important role in
social decision-making processes. Yet it remains difficult to isolate the effect
of self-construal in a comparative approach. Therefore, we used priming
methodology in three studies to induce either an independent or interdependent
mindset to test direct consequences on fairness considerations. Specifically, we
asked whether participants would accept an unfair ultimatum game offer: a split
of 10 euros, where the participant is allocated the marginal share of 3 and the
proposer 7. If the participant refuses, neither gets paid. In the first study, we
used the well-known similarities and differences prime. Here, activating an
interdependent mindset decreased rejection of the unfair offer compared to the
independent mindset and control condition, but only in females. The prime did not
affect males. In the second and third study we modified our university's mission
statement to instead include either independent or interdependent values. Females
displayed a similar direction of effects; in males however, activating an
interdependent mindset increased rejection. Taken together, the results show that
whether participants accept or reject an unfair offer depends on both their
gender and the self-construal prime. The results were interpreted using the
distinction between relational independence that has been associated with
females, and collective interdependence, that has been associated with males.
Possible consequences for future studies are discussed.
PMID- 28421020
TI - Social Dominance Orientation, Dispositional Empathy, and Need for Cognitive
Closure Moderate the Impact of Empathy-Skills Training, but Not Patient Contact,
on Medical Students' Negative Attitudes toward Higher-Weight Patients.
AB - Anti-fat bias in healthcare providers and medical students has serious
implications for quality of care of higher-weight patients. Studies of
interventions aimed at reducing anti-fat attitudes in medical students have
generally been disappointing, with little enduring effect. It is possible that
some students may be more receptive to prejudice-reducing influences than others,
due to underlying differences in their personal characteristics. It is also
possible that attitudes toward patients, specifically, may differ from anti-fat
attitudes in general, and prejudice-reduction effectiveness on patient-specific
attitudes has not yet been evaluated. The present study explored the effect on
general and patient-specific anti-fat attitudes of (1) contact with higher-weight
individuals prior to and during medical school; and (2) training designed to
increase medical students' empathy toward patients by encouraging them to take
the patient's perspective during clinical encounters. The moderating role of
individual difference factors on effectiveness of contact and student-reported
hours of empathy training on patient-specific attitudes was assessed. A total of
3,576 students enrolled across 49 US medical schools completed an online survey
at the start of their first year of medical school and at the end of their fourth
year. Favorable contact experience with higher-weight patients predicted improved
attitudes toward heavier patients after 4 years of medical school, and appeared
sufficient to partially offset the effects of dislike of higher-weight
individuals at baseline. The impact of favorable contact on general anti-fat
attitudes was less strong, highlighting the importance of using target-specific
outcome measures. The positive effects of favorable contact on attitudes toward
higher-weight patients did not differ based on students' baseline levels of
social dominance orientation, dispositional empathy, or need for cognitive
closure. In contrast, the effectiveness of training did vary by student
characteristics, generally being more effective in students who were more
egalitarian and empathic at baseline, with little effect, or even adverse effects
in students low in these traits. Overall, however, perspective-taking training
produced only small improvements in attitudes toward higher-weight patients.
PMID- 28421021
TI - Employee Wellbeing: Evaluating a Wellbeing Intervention in Two Settings.
AB - This research presents two studies conducted to evaluate the Wellbeing Game in
two different contexts: In a student sample and in an organizational setting.
Study 1 investigated the efficacy of the Wellbeing Game, in terms of its effect
of wellbeing, stress, and an image valence test, among 60 university students.
The results showed that after playing the Wellbeing Game, students reported a
significant positive change in wellbeing compared to those who did not play the
Wellbeing Game, but there was no decrease in stress or any change in
classification of image valence. Study 2 evaluated the Wellbeing Game in an
organizational context. Employees (n = 52) in a financial organization played the
Wellbeing Game for 4 weeks and answered survey questions about wellbeing and
stress at the beginning and end of this period. The results showed that after
playing the Wellbeing Game, employees reported lower stress levels, and higher
wellbeing levels for those who felt that it had helped them connect more with
colleagues. The results from the two studies provide preliminary support that the
Wellbeing Game may be an effective wellbeing intervention tool in both an
organization and a non-organizational context.
PMID- 28421022
TI - Commentary: How to Make the Ghosts in my Bedroom Disappear? Focused-Attention
Meditation Combined with Muscle Relaxation (MR Therapy)-A Direct Treatment
Intervention for Sleep Paralysis.
PMID- 28421023
TI - Editorial: Phonology in the Bilingual and Bidialectal Lexicon.
PMID- 28421024
TI - Family and Individual Risk and Protective Factors of Depression among Chinese
Migrant Children with Oppositional Defiant Disorder Symptoms.
AB - Migrant children reached 35.81 million in China and were vulnerable to serious
emotional problems including depression. The present study aimed to identify the
family and individual risk and protective factors for depression in an at-risk
sample of Chinese migrant children. Participants were 368 children (9.47 +/- 1.46
years old, 73.4% boys) who had at least one symptom of Oppositional Defiant
Disorder symptoms (ODD) and their parents in Mainland China. Risk and protective
factors within both family (i.e., family maltreatment and family functioning) and
individual (i.e., automatic thoughts and resilience) perspectives. Family
maltreatment and negative automatic thoughts served as risk factors in relation
to children's depression. Further, automatic thoughts mediated the relationship
between family maltreatment and children's depression. Family functioning
(cohesion, but bot adaptability) and individual resilience could buffer the
effects of risk factors in the Structure Emotion Model such that both cohesion
and resilience moderated the relationship between family maltreatment and
children's automatic thoughts only. Our findings highlighted the urgent need to
decrease risk factors and increase protective factors of both family and child
individual characteristics in prevention and intervention depression among
migrant children with ODD symptoms in China.
PMID- 28421025
TI - The Use of Lausanne Trilogue Play in Three Cases of Gastroschisis Diagnosed
during Pregnancy.
AB - From pregnancy to the 1st years of a child's life, families develop and increase
representations and interactive competences toward the child. Prenatal diagnosis
of a severe fetus' defect could profoundly alter the parental perception and
development of these representations. The aim of the study was to evaluate
triadic interactions in families, whose baby was prenatally diagnosed with severe
gastroschisis. Three families took part in the preliminary case study, which was
carried out when the babies were 6 months old. The Lausanne Trilogue Play shows
that prenatal diagnosis of fetal malformation may affect family triadic
interactions as follows: (a) parents, especially mothers, tend to be intrusive
during the play; (b) parents presents maladjustments in the child stimulations,
especially during the third part, when both parents have to simultaneously
interact with the baby; (c) parents experience difficulties in creating a space
that allows them to communicate directly with each other, leaving the child in a
peripheral position. Observational data and clinical implications are discussed.
PMID- 28421026
TI - Keeping the Spirits Up: The Effect of Teachers' and Parents' Emotional Support on
Children's Working Memory Performance.
AB - Working memory, used to temporarily store and mentally manipulate information, is
important for children's learning. It is therefore valuable to understand which
(contextual) factors promote or hinder working memory performance. Recent
research shows positive associations between positive parent-child and teacher
student interactions and working memory performance and development. However, no
study has yet experimentally investigated how parents and teachers affect working
memory performance. Based on attachment theory, the current study investigated
the role of parent and teacher emotional support in promoting working memory
performance by buffering the negative effect of social stress. Questionnaires and
an experimental session were completed by 170 children from grade 1 to 2 (Mage =
7 years 6 months, SD = 7 months). Questionnaires were used to assess children's
perceptions of the teacher-student and parent-child relationship. During an
experimental session, working memory was measured with the Corsi task backward
(Milner, 1971) in a pre- and post-test design. In-between the tests stress was
induced in the children using the Cyberball paradigm (Williams et al., 2000).
Emotional support was manipulated (between-subjects) through an audio message
(either a weather report, a supportive message of a stranger, a supportive
message of a parent, or a supportive message of a teacher). Results of repeated
measures ANOVA showed no clear effect of the stress induction. Nevertheless, an
effect of parent and teacher support was found and depended on the quality of the
parent-child relationship. When children had a positive relationship with their
parent, support of parents and teachers had little effect on working memory
performance. When children had a negative relationship with their parent, a
supportive message of that parent decreased working memory performance, while a
supportive message from the teacher increased performance. In sum, the current
study suggests that parents and teachers can support working memory performance
by being supportive for the child. Teacher support is most effective when the
child has a negative relationship with the parent. These insights can give
direction to specific measures aimed at preventing and resolving working memory
problems and related issues.
PMID- 28421027
TI - Universal Visual Features Might Be Necessary for Fluent Reading. A Longitudinal
Study of Visual Reading in Braille and Cyrillic Alphabets.
AB - It has been hypothesized that efficient reading is possible because all reading
scripts have been matched, through cultural evolution, to the natural
capabilities of the visual cortex. This matching has resulted in all scripts
being made of line-junctions, such as T, X, or L. Our aim was to test a critical
prediction of this hypothesis: visual reading in an atypical script that is
devoid of line-junctions (such as the Braille alphabet read visually) should be
much less efficient than reading in a "normal" script (e.g., Cyrillic). Using a
lexical decision task, we examined Visual Braille reading speed and efficiency in
sighted Braille teachers. As a control, we tested learners of a natural visual
script, Cyrillic. Both groups participated in a two semester course of either
visual Braille or Russian while their reading speed and accuracy was tested at
regular intervals. The results show that visual Braille reading is slow, prone to
errors and highly serial, even in Braille readers with years of prior reading
experience. Although subjects showed some improvements in their visual Braille
reading accuracy and speed following the course, the effect of word length on
reading speed (typically observed in beginning readers) was remained very
sizeable through all testing sessions. These results are in stark contrast to
Cyrillic, a natural script, where only 3 months of learning were sufficient to
achieve relative proficiency. Taken together, these results suggest that visual
features such as line junctions and their combinations might be necessary for
efficient reading.
PMID- 28421028
TI - Adult-Onset Niemann-Pick Disease Type C: Rapid Treatment Initiation Advised but
Early Diagnosis Remains Difficult.
AB - Niemann-Pick type C disease (NP-C) presents with heterogeneous neurological and
psychiatric symptoms. Adult onset is rare and possibly underdiagnosed due to
frequent lack of specific and obvious key symptoms. For both early and
adolescent/adult onset, the available data from studies and case reports describe
a positive effect of Miglustat (symptom relief or stabilization). However, due to
the low frequency of NP-C, experience with this therapy is still limited. We
describe two adult-onset cases of NP-C. In both cases, vertical supranuclear gaze
palsy was not recognized at symptom onset. Correct diagnosis was delayed from
onset of symptoms by more than 10 years. The video demonstrates the broad
spectrum of symptoms in later stages of the disease. Compared with published
data, the treatment outcome observed in our cases after delayed initiation of
Miglustat therapy was disappointing, with continuing disease progression in both
cases. Thus, early treatment initiation could be necessary to achieve a good
symptomatic effect. Hence, early biochemical testing for NP-C should be
considered in patients suffering from atypical neurological/neuropsychological
and psychiatric symptoms, even in cases of uncertainty.
PMID- 28421029
TI - A Historical View of Motion Sickness-A Plague at Sea and on Land, Also with
Military Impact.
AB - Seasickness and its triggers, symptoms, and preventive measures were well known
in antiquity. This chapter is based on an analysis of descriptions of motion
sickness, in particular seasickness, in ancient Greek, Roman, and Chinese
literature. A systematic search was made from the Greek period beginning with
Homer in 800 BC to the late Roman period and ending with Aetios Amidenos in 600
AD, as well as in the Chinese medical classics dating from around 300 AD. Major
aspects are the following: body movements caused by waves were identified in all
cultures as the critical stimuli. The ancient Greeks and Romans knew that other
illnesses and the mental state could precipitate seasickness and that experienced
sailors were highly resistant to it (habituation). The Chinese observed that
children were particularly susceptible to motion sickness; they first described
the type of motion sickness induced by traveling in carts (cart-sickness) or
being transported on a litter or in a sedan chair (litter-sickness). The western
classics recommended therapeutic measures like fasting or specific diets,
pleasant fragrancies, medicinal plants like white hellebore (containing various
alkaloids), or a mixture of wine and wormwood. The East knew more unusual
measures, such as drinking the urine of young boys, swallowing white sand-syrup,
collecting water drops from a bamboo stick, or hiding earth from the kitchen
hearth under the hair. The Greek view of the pathophysiology of seasickness was
based on the humoral theory of Empedokles and Aristoteles and differed from the
Chinese medicine of correspondences, which attributed malfunctions to certain
body substances and the life force Qi. Many sources emphasized the impact of
seasickness on military actions and famous naval battles such as the Battle of
the Red Cliff, which marked the end of the Han dynasty in China, or the defeat of
the Spanish Armada by the English in 1588. A peculiar form of motion sickness is
associated with Napoleon's camel corps during the Egyptian campaign of 1798/1799,
a sickness induced by riding on a camel. Thus, motion sickness in antiquity was
known as a physiological response to unadapted body motions during passive
transportation as well as a plague at sea.
PMID- 28421030
TI - Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.
AB - INTRODUCTION: In tinnitus treatment, there is a tendency to shift from a "one
size fits all" to a more individual, patient-tailored approach. Insight in the
heterogeneity of the tinnitus spectrum might improve the management of tinnitus
patients in terms of choice of treatment and identification of patients with
severe mental distress. The goal of this study was to identify subgroups in a
large group of tinnitus patients. METHODS: Data were collected from patients with
severe tinnitus complaints visiting our tertiary referral tinnitus care group at
the University Medical Center Groningen. Patient-reported and physician-reported
variables were collected during their visit to our clinic. Cluster analyses were
used to characterize subgroups. For the selection of the right variables to enter
in the cluster analysis, two approaches were used: (1) variable reduction with
principle component analysis and (2) variable selection based on expert opinion.
RESULTS: Various variables of 1,783 tinnitus patients were included in the
analyses. Cluster analysis (1) included 976 patients and resulted in a four
cluster solution. The effect of external influences was the most discriminative
between the groups, or clusters, of patients. The "silhouette measure" of the
cluster outcome was low (0.2), indicating a "no substantial" cluster structure.
Cluster analysis (2) included 761 patients and resulted in a three-cluster
solution, comparable to the first analysis. Again, a "no substantial" cluster
structure was found (0.2). CONCLUSION: Two cluster analyses on a large database
of tinnitus patients revealed that clusters of patients are mostly formed by a
different response of external influences on their disease. However, both cluster
outcomes based on this dataset showed a poor stability, suggesting that our
tinnitus population comprises a continuum rather than a number of clearly defined
subgroups.
PMID- 28421031
TI - Fatal Outcome of European Tick-borne Encephalitis after Vaccine Failure.
AB - Tick-borne encephalitis is a viral disease affecting the central nervous system.
It is endemic in Switzerland with 200-250 notified cases annually. Active
immunization is effective for persons in all age groups. Vaccine failure is rare,
in particular after a completed vaccination course. Here, we describe the case of
67-year-old man with a fatal outcome despite vaccination. The diagnosis was
confirmed by extensive postmortem analyses. The diagnostic challenges of vaccine
failure in tick-borne encephalitis and the dynamics of the immune response in
vaccination breakthrough are discussed.
PMID- 28421033
TI - Orthostatic Hypotension Predicts Cognitive Impairment in the Elderly: Findings
from a Cohort Study.
AB - BACKGROUND: Orthostatic hypotension (OH) is a known risk factor for cerebral
ischemia, but its correlation with cognitive impairment (CI) is not well
established. OBJECTIVE: The aim of this study is to explore the relationship
between OH and CI in the elderly. METHODS: The study group consisted of 44 OH
patients who presented with drowsiness, vertigo, and fatigue between January 2009
and December 2011 (OH group). Eighty-eight healthy elderly were paired with those
in the OH group in a 1:2 based on their education levels (NOH group). Baseline
sociodemographic information and cognition-related measures were collected for
both groups. Cognitive function was assessed 4 years later using MMSE. RESULTS:
The overall incidence of CI was 14.0% among the 114 subjects who completed the
follow-up assessment. There was a significant difference in the incidence of CI
between the OH group (23.7%) and the NOH group (9.2%) (chi2 = 4.399, P = 0.036).
After excluding the influence of age (OR = 1.199, 95% CI: 1.072-1.340, P = 0.001)
and education years (OR = 0.568, 95% CI: 0.371-0.869, P = 0.009), OH (OR = 4.047,
95% CI: 1.144-14.313, P = 0.030) became an independent risk factor for CI.
CONCLUSION: OH can lead to CI. We suggest that future studies, with a larger
sample size, use OH exposure time instead of OH exposure population to verify the
conclusion of this study.
PMID- 28421032
TI - Spasticity, Motor Recovery, and Neural Plasticity after Stroke.
AB - Spasticity and weakness (spastic paresis) are the primary motor impairments after
stroke and impose significant challenges for treatment and patient care.
Spasticity emerges and disappears in the course of complete motor recovery.
Spasticity and motor recovery are both related to neural plasticity after stroke.
However, the relation between the two remains poorly understood among clinicians
and researchers. Recovery of strength and motor function is mainly attributed to
cortical plastic reorganization in the early recovery phase, while reticulospinal
(RS) hyperexcitability as a result of maladaptive plasticity, is the most
plausible mechanism for poststroke spasticity. It is important to differentiate
and understand that motor recovery and spasticity have different underlying
mechanisms. Facilitation and modulation of neural plasticity through
rehabilitative strategies, such as early interventions with repetitive goal
oriented intensive therapy, appropriate non-invasive brain stimulation, and
pharmacological agents, are the keys to promote motor recovery. Individualized
rehabilitation protocols could be developed to utilize or avoid the maladaptive
plasticity, such as RS hyperexcitability, in the course of motor recovery.
Aggressive and appropriate spasticity management with botulinum toxin therapy is
an example of how to create a transient plastic state of the neuromotor system
that allows motor re-learning and recovery in chronic stages.
PMID- 28421034
TI - Is the Headache in Patients with Vestibular Migraine Attenuated by Vestibular
Rehabilitation?
AB - BACKGROUND: Vestibular rehabilitation is the most effective treatment for
dizziness due to vestibular dysfunction. Given the biological relationship
between vestibular symptoms and headache, headache in patients with vestibular
migraine (VM) could be improved by vestibular rehabilitation that leads to the
improvement of dizziness. This study aimed to compare the effects of vestibular
rehabilitation on headache and other outcomes relating to dizziness, and the
psychological factors in patients with VM patients, patients with dizziness and
tension-type headache, and patients without headache. METHODS: Our participants
included 251 patients with dizziness comprising 28 patients with VM, 79 patients
with tension-type headache, and 144 patients without headache. Participants were
hospitalized for 5 days and taught to conduct a vestibular rehabilitation
program. They were assessed using the Dizziness Handicap Inventory (DHI),
Headache Impact Test (HIT-6), Hospital Anxiety and Depression Scale (HADS), and
Somatosensory Catastrophizing Scale (SSCS) and underwent center of gravity
fluctuation measurement as an objective dizziness severity index before, 1 month
after, and 4 months after their hospitalization. RESULTS: The VM and tension-type
headache groups demonstrated a significant improvement in the HIT-6 score with
improvement of the DHI, HADS, SSCS, and a part of the objective dizziness index
that also shown in patients without headache following vestibular rehabilitation.
The change in HIT-6 during rehabilitation in the VM group was positively
correlated with changes in the DHI and anxiety in the HADS. Changes in the HIT-6
in tension-type headache group positively correlated with changes in anxiety and
SSCS. CONCLUSION: Vestibular rehabilitation contributed to improvement of
headache both in patients with VM and patients with dizziness and tension-type
headache, in addition to improvement of dizziness and psychological factors.
Improvement in dizziness following vestibular rehabilitation could be associated
with the improvement of headache more prominently in VM compared with comorbid
tension-type headache.
PMID- 28421035
TI - Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes.
AB - BACKGROUND: Most antiepileptic drugs (AEDs) inhibit seizure generation by acting
on voltage-dependent ion channels. Voltage-dependent sodium and calcium channels
are commonly expressed in brain and heart, suggesting that AEDs may have
considerable cardiodepressive effects, thereby facilitating sudden cardiac death
as a potential cause of sudden unexpected death in epilepsy. Here, we
investigated the effects of carbamazepine (CBZ), lamotrigine (LTG), and
levetiracetam (LEV) alone and in combination on the shortening properties of
isolated ventricular cardiomyocytes of wild-type mice. METHODS: Properties of
murine cardiomyocytes were determined by recording the sarcomere shortening with
a video imaging system before, during, and after administration of AEDs in
different concentrations and combinations. We assessed (i) the number of
successful shortenings during continuous electrical stimulation
(electromechanical coupling) and (ii) the shortening amplitude as well as other
shortening-related properties upon repetitive electrical stimulation at 4 Hz.
Data are given as mean +/- SEM. RESULTS: At 100 MUM, CBZ (10 cells), LTG (11
cells), and LEV (11 cells) alone had no effect on the electromechanical coupling
but reversibly reduced shortening amplitudes by 15 +/- 4, 24 +/- 3, and 11 +/-
3%, respectively. Increasing the LTG concentration to 250 (21 cells) and 500 MUM
(4 cells) reversibly inhibited the electromechanical coupling in 62 and 100% of
the experiments. Importantly, simultaneous application of CBZ, LTG, and LEV at
100 MUM also impaired the electromechanical coupling in 8 of 19 cardiomyocytes
(42%) and reduced the shortening amplitude by 21 +/- 4%. CONCLUSION: Our data
show that AEDs reversibly impair cardiac excitation and contraction. Importantly,
the blocking effect on electromechanical coupling appears to be additive when
different AEDs are simultaneously applied. The translational value of these
experimental findings into clinical practice is limited. Our results, however,
suggest that rationale AED therapy may be important with respect to cardiac side
effects and potential facilitation of serious cardiac dysfunction especially when
AEDs are used in combination or at very high doses.
PMID- 28421036
TI - Genetics of Thyroid-Stimulating Hormone Receptor-Relevance for Autoimmune Thyroid
Disease.
AB - Production of thyroid-stimulating hormone receptor (TSHR) antibodies represents
the hallmark of Graves' disease (GD) pathogenesis. Thus, for more than two
decades the TSHR gene has been at the center of studies intended to elucidate its
contribution to disease pathology. The advent of genome-wide association
technology allowed to establish a strong association of the TSHR gene with GD.
Subsequent fine-mapping studies narrowed the disease-susceptibility region to a
40 kb sequence in intron 1, where at least five GD-associated SNPs in tight
linkage disequilibrium were identified. The current challenge is to understand
the functional mechanisms by which these polymorphisms modify physiological
processes and trigger disease. The aim of this review is to summarize the current
knowledge on the role of the TSHR gene in GD pathogenesis, which has been gained
through linkage and association studies, as well as to discuss the emerging
mechanisms underlying biological implications of TSHR variants in the development
of GD.
PMID- 28421038
TI - Bacteriophages against Serratia as Fish Spoilage Control Technology.
AB - Bacteria of the genus Serratia, mainly S. proteamaculans and S. fonticola, are
important spoilage agents in Atlantic horse mackerel (Trachurus trachurus). In
order to evaluate whether bacteriophages against Serratia could delay the
spoilage process, 11 viral strains active against this genus were isolated from
food and best candidate was applied to fresh mackerel filets. All the phages
belong to the Siphoviridae and Podoviridae families and were active at
multiplicity of infection (MOI) levels below 1:1 in Long & Hammer broth. The
ability of phage AZT6 to control Serratia populations in real food was tested in
Atlantic horse mackerel extract and applied to fresh mackerel filets. Treatment
with high phage concentration (MOI 350:1, initial Serratia population 3.9 +/- 0.3
Log cfu/g) can reduce the Serratia populations up to 90% during fish storage (a
maximum of 6 days) at low temperatures (6 degrees C). Bacterial inhibition was
dependent on the bacteriophage dosage, and MOI of 10:1 or lower did not
significantly affect the Serratia populations.
PMID- 28421037
TI - Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism.
AB - Metabolic disorders, particularly aberrations in lipid homeostasis, such as
obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest
together as the metabolic syndrome (MetS). Despite major advances in our
understanding of the pathogenesis of these disorders, the prevalence of the MetS
continues to rise. It is becoming increasingly apparent that intermediary
metabolism within the central nervous system is a major contributor to the
regulation of systemic metabolism. In particular, lipid metabolism within the
brain is tightly regulated to maintain neuronal structure and function and may
signal nutrient status to modulate metabolism in key peripheral tissues such as
the liver. There is now a growing body of evidence to suggest that fatty acid
(FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites
may signal nutritional sufficiency and may decrease hepatic glucose production,
lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted
the existence of liver-related neurons that have the potential to direct such
signals through parasympathetic and sympathetic nervous system activity. However,
to date whether these liver-related neurons are FA sensitive remain to be
determined. The findings discussed in this review underscore the importance of
the autonomic nervous system in the regulation of systemic metabolism and
highlight the need for further research to determine the key features of FA
neurons, which may serve as novel therapeutic targets for the treatment of
metabolic disorders.
PMID- 28421039
TI - Population Structure of Sclerotinia subarctica and Sclerotinia sclerotiorum in
England, Scotland and Norway.
AB - Sclerotinia species are important fungal pathogens of a wide range of crops and
wild host plants. While the biology and population structure of Sclerotinia
sclerotiorum has been well-studied, little information is available for the
related species S. subarctica. In this study, Sclerotinia isolates were collected
from different crop plants and the wild host Ranuculus ficaria (meadow buttercup)
in England, Scotland, and Norway to determine the incidence of Sclerotinia
subarctica and examine the population structure of this pathogen for the first
time. Incidence was very low in England, comprising only 4.3% of isolates while
moderate and high incidence of S. subarctica was identified in Scotland and
Norway, comprising 18.3 and 48.0% of isolates respectively. Characterization with
eight microsatellite markers identified 75 haplotypes within a total of 157
isolates over the three countries with a few haplotypes in Scotland and Norway
sampled at a higher frequency than the rest across multiple locations and host
plants. In total, eight microsatellite haplotypes were shared between Scotland
and Norway while none were shared with England. Bayesian and principal component
analyses revealed common ancestry and clustering of Scottish and Norwegian S.
subarctica isolates while English isolates were assigned to a separate population
cluster and exhibited low diversity indicative of isolation. Population structure
was also examined for S. sclerotiorum isolates from England, Scotland, Norway,
and Australia using microsatellite data, including some from a previous study in
England. In total, 484 haplotypes were identified within 800 S. sclerotiorum
isolates with just 15 shared between England and Scotland and none shared between
any other countries. Bayesian and principal component analyses revealed a common
ancestry and clustering of the English and Scottish isolates while Norwegian and
Australian isolates were assigned to separate clusters. Furthermore, sequencing
part of the intergenic spacer (IGS) region of the rRNA gene resulted in 26 IGS
haplotypes within 870 S. sclerotiorum isolates, nine of which had not been
previously identified and two of which were also widely distributed across
different countries. S. subarctica therefore has a multiclonal population
structure similar to S. sclerotiorum, but has a different ancestry and
distribution across England, Scotland, and Norway.
PMID- 28421040
TI - Isolation and Molecular Characterization of Novel Chlorpyrifos and 3,5,6
trichloro-2-pyridinol-degrading Bacteria from Sugarcane Farm Soils.
AB - Chlorpyrifos (CP) is one of the most widely used organophosphate pesticides in
agriculture worldwide, but its extensive use has led to the contamination of
various soil and water systems. Microbial bioremediation is considered to be one
of the most viable options for the removal of CP from the environment; however,
little is known about the soil bacterial diversity that degrade CP. Sequential
soil and liquid culture enrichments enabled the isolation of bacterial CP
degraders with sequence homologies to Xanthomonas sp., Pseudomonas sp., and
Rhizobium sp. The efficacy of the three isolated strains: Xanthomonas sp. 4R3-M1,
Pseudomonas sp. 4H1-M3, and Rhizobium sp. 4H1-M1 was further investigated for
biodegradation of CP and its primary metabolic product, 3,5,6-trichloro-2
pyridinol (TCP). The results indicate that all three bacterial strains almost
completely metabolized CP (10 mg/L) and TCP, occurring as a metabolic degradation
product, in mineral salt media as a sole source of carbon and nitrogen. The
isolated bacterial strains Xanthomonas sp. 4R3-M1 and Pseudomonas sp. 4H1-M3
could also degrade TCP (10 mg/L) as a sole carbon and nitrogen source, when
provided externally. Thus, these bacterial strains may be effective in practical
application of bioremediation of both CP and TCP.
PMID- 28421041
TI - Metagenome-Wide Association Study and Machine Learning Prediction of Bulk Soil
Microbiome and Crop Productivity.
AB - Areas within an agricultural field in the same season often differ in crop
productivity despite having the same cropping history, crop genotype, and
management practices. One hypothesis is that abiotic or biotic factors in the
soils differ between areas resulting in these productivity differences. In this
study, bulk soil samples collected from a high and a low productivity area from
within six agronomic fields in Illinois were quantified for abiotic and biotic
characteristics. Extracted DNA from these bulk soil samples were shotgun
sequenced. While logistic regression analyses resulted in no significant
association between crop productivity and the 26 soil characteristics, principal
coordinate analysis and constrained correspondence analysis showed crop
productivity explained a major proportion of the taxa variance in the bulk soil
microbiome. Metagenome-wide association studies (MWAS) identified more
Bradyrhizodium and Gammaproteobacteria in higher productivity areas and more
Actinobacteria, Ascomycota, Planctomycetales, and Streptophyta in lower
productivity areas. Machine learning using a random forest method successfully
predicted productivity based on the microbiome composition with the best accuracy
of 0.79 at the order level. Our study showed that crop productivity differences
were associated with bulk soil microbiome composition and highlighted several
nitrogen utility-related taxa. We demonstrated the merit of MWAS and machine
learning for the first time in a plant-microbiome study.
PMID- 28421042
TI - Mosquito Microbiome Dynamics, a Background for Prevalence and Seasonality of West
Nile Virus.
AB - Symbiotic microbial communities augment host phenotype, including defense against
pathogen carriage and infection. We sampled the microbial communities in 11 adult
mosquito host species from six regions in southern Ontario, Canada over 3 years.
Of the factors examined, we found that mosquito species was the largest driver of
the microbiota, with remarkable phylosymbiosis between host and microbiota.
Seasonal shifts of the microbiome were consistently repeated over the 3-year
period, while region had little impact. Both host species and seasonal shifts in
microbiota were associated with patterns of West Nile virus (WNV) in these
mosquitoes. The highest prevalence of WNV, with a seasonal spike each year in
August, was in the Culex pipiens/restuans complex, and high WNV prevalence
followed a decrease in relative abundance of Wolbachia in this species. Indeed,
mean temperature, but not precipitation, was significantly correlated with
Wolbachia abundance. This suggests that at higher temperatures Wolbachia
abundance is reduced leading to greater susceptibility to WNV in the subsequent
generation of C. pipiens/restuans hosts. Different mosquito genera harbored
significantly different bacterial communities, and presence or abundance of
Wolbachia was primarily associated with these differences. We identified several
operational taxonomic units (OTUs) of Wolbachia that drive overall microbial
community differentiation among mosquito taxa, locations and timepoints. Distinct
Wolbachia OTUs were consistently found to dominate microbiomes of Cx.
pipiens/restuans, and of Coquilletidia perturbans. Seasonal fluctuations of
several other microbial taxa included Bacillus cereus, Enterococcus,
Methylobacterium, Asaia, Pantoea, Acinetobacter johnsonii, Pseudomonas, and
Mycoplasma. This suggests that microbiota may explain some of the variation in
vector competence previously attributed to local environmental processes,
especially because Wolbachia is known to affect carriage of viral pathogens.
PMID- 28421043
TI - Outlining Core Pathways of Amyloid Toxicity in Bacteria with the RepA-WH1
Prionoid.
AB - The synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible
amyloid proteinopathy in Escherichia coli that inhibits growth and eventually
kills the cells. Recent in vitro studies show that RepA-WH1 builds pores through
model lipid membranes, suggesting a possible mechanism for bacterial cell death.
By comparing acutely (A31V) and mildly (DeltaN37) cytotoxic mutant variants of
the protein, we report here that RepA-WH1(A31V) expression decreases the
intracellular osmotic pressure and compromise bacterial viability under either
aerobic or anaerobic conditions. Both are effects expected from threatening
membrane integrity and are in agreement with findings on the impairment by RepA
WH1(A31V) of the proton motive force (PMF)-dependent transport of ions (Fe3+) and
ATP synthesis. Systems approaches reveal that, in aerobiosis, the PMF-independent
respiratory dehydrogenase NdhII is induced in response to the reduction in
intracellular levels of iron. While NdhII is known to generate H2O2 as a by
product of the autoxidation of its FAD cofactor, key proteins in the defense
against oxidative stress (OxyR, KatE), together with other stress-resistance
factors, are sequestered by co-aggregation with the RepA-WH1(A31V) amyloid. Our
findings suggest a route for RepA-WH1 toxicity in bacteria: a primary hit of
damage to the membrane, compromising bionergetics, triggers a stroke of oxidative
stress, which is exacerbated due to the aggregation-dependent inactivation of
enzymes and transcription factors that enable the cellular response to such
injury. The proteinopathy caused by the prion-like protein RepA-WH1 in bacteria
recapitulates some of the core hallmarks of human amyloid diseases.
PMID- 28421044
TI - Comparative Genomics of Glossina palpalis gambiensis and G. morsitans morsitans
to Reveal Gene Orthologs Involved in Infection by Trypanosoma brucei gambiense.
AB - Blood-feeding Glossina palpalis gambiense (Gpg) fly transmits the single-celled
eukaryotic parasite Trypanosoma brucei gambiense (Tbg), the second Glossina fly
African trypanosome pair being Glossina morsitans/T.brucei rhodesiense. Whatever
the T. brucei subspecies, whereas the onset of their developmental program in the
zoo-anthropophilic blood feeding flies does unfold in the fly midgut, its
completion is taking place in the fly salivary gland where does emerge a low size
metacyclic trypomastigote population displaying features that account for its
establishment in mammals-human individuals included. Considering that the two
Glossina-T. brucei pairs introduced above share similarity with respect to the
developmental program of this African parasite, we were curious to map on the
Glossina morsitans morsitans (Gmm), the Differentially Expressed Genes (DEGs) we
listed in a previous study. Briefly, using the gut samples collected at days 3,
10, and 20 from Gpg that were fed or not at day 0 on Tbg-hosting mice, these DGE
lists were obtained from RNA seq-based approaches. Here, post the mapping on the
quality controlled DEGs on the Gmm genome, the identified ortholog genes were
further annotated, the resulting datasets being compared. Around 50% of the Gpg
DEGs were shown to have orthologs in the Gmm genome. Under one of the three
Glossina midgut sampling conditions, the number of DEGs was even higher when
mapping on the Gmm genome than initially recorded. Many Gmm genes annotated as
"Hypothetical" were mapped and annotated on many distinct databases allowing some
of them to be properly identified. We identify Glossina fly candidate genes
encoding (a) a broad panel of proteases as well as (b) chitin-binding proteins,
(c) antimicrobial peptide production-Pro3 protein, transferrin, mucin, atttacin,
cecropin, etc-to further select in functional studies, the objectives being to
probe and validated fly genome manipulation that prevents the onset of the
developmental program of one or the other T. brucei spp. stumpy form sampled by
one of the other bloodfeeding Glossina subspecies.
PMID- 28421045
TI - Cranberry Juice and Combinations of Its Organic Acids Are Effective against
Experimental Urinary Tract Infection.
AB - The antibacterial effect of cranberry juice and the organic acids therein on
infection by uropathogenic Escherichia coli was studied in an experimental mouse
model of urinary tract infection (UTI). Reduced bacterial counts were found in
the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially
available cranberry juice cocktail also significantly reduced (P < 0.01)
bacterial populations in the bladder, as did the hydrophilic fraction of
cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the
preponderant organic acids in cranberry juice, were tested in combination and
individually. The four organic acids also decreased bacterial levels in the
bladder when administered together (P < 0.001), and so did the combination of
malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The
other tested combinations of the organic acids, and the acids administered
singly, did not have any effect in the UTI model. Apparently, the antibacterial
effect of the organic acids from cranberry juice on UTI can be obtained by
administering a combination of malic acid and either citric or quinic acid. This
study show for the first time that cranberry juice reduce E. coli colonization of
the bladder in an experimental mouse model of urinary tract infection and that
the organic acids are active agents.
PMID- 28421046
TI - Horses in Denmark Are a Reservoir of Diverse Clones of Methicillin-Resistant and
Susceptible Staphylococcus aureus.
AB - Denmark is a country with high prevalence of livestock-associated methicillin
resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 in pigs. Even
though pig farming is regarded as the main source of human infection or
colonization with MRSA CC398, 10-15% of the human cases appear not to be linked
to pigs. Following the recent reports of MRSA CC398 in horses in other European
countries and the lack of knowledge on S. aureus carriage in this animal species,
we carried out a study to investigate whether horses constitute a reservoir of
MRSA CC398 in Denmark, and to gain knowledge on the frequency and genetic
diversity of S. aureus in horses, including both methicillin-resistant and
susceptible S. aureus (MSSA). Nasal swabs were collected from 401 horses
originating from 74 farms, either at their farms or prior to admission to
veterinary clinics. Following culture on selective media, species identification
by MALDI-TOF MS and MRSA confirmation by standard PCR-based methods, S. aureus
and MRSA were detected in 54 (13%) and 17 (4%) horses originating from 30 (40%)
and 7 (9%) farms, respectively. Based on spa typing, MSSA differed genetically
from MRSA isolates. The spa type prevalent among MSSA isolates was t127 (CC1),
which was detected in 12 horses from 11 farms and represents the most common S.
aureus clone isolated from human bacteremia cases in Denmark. Among the 17 MRSA
carriers, 10 horses from three farms carried CC398 t011 harboring the immune
evasion cluster (IEC), four horses from two farms carried IEC-negative CC398
t034, and three horses from two farms carried a mecC-positive MRSA lineage
previously associated with wildlife and domestic ruminants (CC130 t528). Based on
whole-genome phylogenetic analysis of the 14 MRSA CC398, t011 isolates belonged
to the recently identified horse-adapted clone in Europe and were closely related
to human t011 isolates from three Danish equine veterinarians, whereas t034
isolates belonged to pig-adapted clones. Our study confirms that horses carry an
equine-specific clone of MRSA CC398 that can be transmitted to veterinary
personnel, and reveals that these animals are exposed to MRSA and MSSA clones
that are likely to originate from livestock and humans, respectively.
PMID- 28421047
TI - Genetic Characterization of the Exceptionally High Heat Resistance of the Non
toxic Surrogate Clostridium sporogenes PA 3679.
AB - Clostridium sporogenes PA 3679 is a non-toxic endospore former that is widely
used as a surrogate for Clostridium botulinum by the food processing industry to
validate thermal processing strategies. PA 3679 produces spores of exceptionally
high heat resistance without botulinum neurotoxins, permitting the use of PA 3679
in inoculated pack studies while ensuring the safety of food processing
facilities. To identify genes associated with this heat resistance, the genomes
of C. sporogenes PA 3679 isolates were compared to several other C. sporogenes
strains. The most significant difference was the acquisition of a second spoVA
operon, spoVA2, which is responsible for transport of dipicolinic acid into the
spore core during sporulation. Interestingly, spoVA2 was also found in some C.
botulinum species which phylogenetically cluster with PA 3679. Most other C.
sporogenes strains examined both lack the spoVA2 locus and are phylogenetically
distant within the group I Clostridium, adding to the understanding that C.
sporogenes are dispersed C. botulinum strains which lack toxin genes. C.
sporogenes strains are thus a very eclectic group, and few strains possess the
characteristic heat resistance of PA 3679.
PMID- 28421049
TI - Transcriptomic and Metabolomics Profiling of Phage-Host Interactions between
Phage PaP1 and Pseudomonas aeruginosa.
AB - The basic biology of bacteriophage-host interactions has attracted increasing
attention due to a renewed interest in the therapeutic potential of
bacteriophages. In addition, knowledge of the host pathways inhibited by phage
may provide clues to novel drug targets. However, the effect of phage on
bacterial gene expression and metabolism is still poorly understood. In this
study, we tracked phage-host interactions by combining transcriptomic and
metabolomic analyses in Pseudomonas aeruginosa infected with a lytic
bacteriophage, PaP1. Compared with the uninfected host, 7.1% (399/5655) of the
genes of the phage-infected host were differentially expressed genes (DEGs); of
those, 354 DEGs were downregulated at the late infection phase. Many of the
downregulated DEGs were found in amino acid and energy metabolism pathways. Using
metabolomics approach, we then analyzed the changes in metabolite levels in the
PaP1-infected host compared to un-infected controls. Thymidine was significantly
increased in the host after PaP1 infection, results that were further supported
by increased expression of a PaP1-encoded thymidylate synthase gene. Furthermore,
the intracellular betaine concentration was drastically reduced, whereas choline
increased, presumably due to downregulation of the choline-glycine betaine
pathway. Interestingly, the choline-glycine betaine pathway is a potential
antimicrobial target; previous studies have shown that betB inhibition results in
the depletion of betaine and the accumulation of betaine aldehyde, the
combination of which is toxic to P. aeruginosa. These results present a detailed
description of an example of phage-directed metabolism in P. aeruginosa. Both
phage-encoded auxiliary metabolic genes and phage-directed host gene expression
may contribute to the metabolic changes observed in the host.
PMID- 28421048
TI - Functional Information Stored in the Conserved Structural RNA Domains of
Flavivirus Genomes.
AB - The genus Flavivirus comprises a large number of small, positive-sense single
stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod
and/or vertebrate host cells. The genus, which has some 70 member species,
includes a number of emerging and re-emerging pathogens responsible for outbreaks
of human disease around the world, such as the West Nile, dengue, Zika, yellow
fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis
viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that
efficiently stores all the information required for the completion of the
infectious cycle. The efficiency of this storage system is attributable to
supracoding elements, i.e., discrete, structural units with essential functions.
This information storage system overlaps and complements the protein coding
sequence and is highly conserved across the genus. It therefore offers
interesting potential targets for novel therapeutic strategies. This review
summarizes our knowledge of the features of flavivirus genome functional RNA
domains. It also provides a brief overview of the main achievements reported in
the design of antiviral nucleic acid-based drugs targeting functional genomic RNA
elements.
PMID- 28421050
TI - Reveromycins A and B from Streptomyces sp. 3-10: Antifungal Activity against
Plant Pathogenic Fungi In vitro and in a Strawberry Food Model System.
AB - This study was conducted to determine the antifungal activity of the metabolites
from Streptomyces sp. 3-10, and to purify and identify the metabolites.
Meanwhile, the taxonomic status of strain 3-10 was re-evaluated. The cultural
filtrates of strain 3-10 in potato dextrose broth were extracted with ethyl
acetate. The resulting crude extract at 1 and 5 MUg/ml inhibited growth of 22
species in 18 genera of plant pathogenic fungi and Oomycetes, accounting for 92%
of the total 24 tested species, suggesting that it has a wide antifungal
spectrum. Two compounds were purified from the crude extract and were identified
as reveromycins A and B, which demonstrated high antifungal activity against
Botrytis cinerea, Mucor hiemails, Rhizopus stolonifer, and Sclerotinia
sclerotiorum under acidic pH conditions. Both the crude extract and reveromycin A
from strain 3-10 at 10, 50, and 100 MUg/ml showed high efficacy in suppression of
strawberry fruit rot caused by the above-mentioned four pathogens. The efficacy
was comparable to that of corresponding commercial fungicides (pyrimethanil,
captan, dimetachlone) used in management of these pathogens. Morphological,
physiological, and phylogenetic characterization showed that strain 3-10 is
closely related to Streptomyces yanglinensis 1307T, representing a novel
phylotype in that species. This study reported a new strain with reveromycins
producing capability. The finding is important for further exploitation of
reveromycins for agricultural use.
PMID- 28421051
TI - In Situ Capture RT-qPCR: A New Simple and Sensitive Method to Detect Human
Norovirus in Oysters.
AB - Human noroviruses (HuNoVs) are the major cause worldwide for non-bacterial acute
gastroenteritis. In this study, we applied a novel viral receptor mediated in
situ capture RT-qPCR (ISC-RT-qPCR) to detect HuNoVs in oysters and compared with
the traditional RT-qPCR method. Ten HuNoVs RT-PCR positive and 5 negative
clinical samples from gastroenteritis patients were used to compare specificity
and sensitivity of ISC-RT-qPCR against that of the RT-qPCR assay. ISC-RT-qPCR had
at a one-log and a two-log increase in sensitivity over that of the RT-qPCR assay
for genotype I (GI) and GII, respectively. Distributions of HuNoVs in oyster
tissues were investigated in artificially inoculated oysters. GI HuNoVs could be
detected in all tissues in inoculated oysters by both ISC-RT-qPCR and RT-qPCR.
GII HuNoVs could only be detected in gills and digestive glands by both methods.
The number of viral genomic copies (vgc) measured by ISC-RT-qPCR was comparable
with RT-qPCR in the detection of GI and GII HuNoVs in inoculated oysters. Thirty
six oyster samples from local market were assayed for HuNoVs by both assays. More
HuNoVs could be detected by ISC-RT-qPCR in retail oysters. The detection rates of
GI HuNoVs in gills, digestive glands, and residual tissues were 33.3, 25.0, and
19.4% by ISC-RT-qPCR; and 5.6, 11.1, and 11.1% by RT-qPCR, respectively. The
detection rates of GII HuNoVs in gills were 2.8% by ISC-RT-qPCR; no GII HuNoV was
detected in these oysters by RT-qPCR. Overall, all results demonstrated that ISC
RT-qPCR is a promising method for detecting HuNoVs in oyster samples.
PMID- 28421052
TI - Whole Genome-Based Amplified Fragment Length Polymorphism Analysis Reveals
Genetic Diversity in Candida africana.
AB - This study aimed at investigating the genetic diversity of a panel of Candida
africana strains recovered from vaginal samples in different countries. All
fungal strains were heterozygous at the mating-type-like locus and belonged to
the genotype A of Candida albicans. Moreover, all examined C. africana strains
lack N-acetylglucosamine assimilation and sequence analysis of the HXK1 gene
showed a distinctive polymorphism that impair the utilization of this amino sugar
in this yeast. Multi-locus sequencing of seven housekeeping genes revealed a
substantial genetic homogeneity among the strains, except for the CaMPIb, SYA1
and VPS13 loci which contributed significantly to the classification of our set
of C. africana strains into six existing diploid sequence types. Amplified
fragment length polymorphism fingerprint analysis yielded greater genotypic
heterogeneity among the C. africana strains. Overall the data reported here show
that in C. africana genetic diversity occurs and the existence of this intriguing
group of C. albicans strains with specific phenotypes associated could be useful
for future comparative studies in order to better understand the genetics and
evolution of this important human pathogen.
PMID- 28421053
TI - Elevated Air Humidity Changes Soil Bacterial Community Structure in the Silver
Birch Stand.
AB - Soil microbes play a fundamental role in forest ecosystems and respond rapidly to
changes in the environment. Simultaneously with the temperature increase the
climate change scenarios also predict an intensified hydrological cycle for the
Baltic Sea runoff region. The aim of this study was to assess the effect of
elevated air humidity on the top soil microbial community structure of a silver
birch (Betula pendula Roth.) stand by using a free air humidity manipulation
facility (FAHM). The bacterial community structures of bulk soil and birch
rhizosphere were analyzed using high-throughput sequencing of bacteria
specific16S rRNA gene fragments and quantification of denitrification related
genes. The increased air humidity altered both bulk soil and rhizosphere
bacterial community structures, and changes in the bacterial communities
initiated by elevated air humidity were related to modified soil abiotic and
biotic variables. Network analysis revealed that variation in soil bacterial
community structural units is explained by altered abiotic conditions such as
increased pH value in bulk soil, while in rhizosphere the change in absorptive
root morphology had a higher effect. Among root morphological traits, the
absorptive root diameter was strongest related to the bacterial community
structure. The changes in bacterial community structures under elevated air
humidity are associated with shifts in C, N, and P turnover as well as mineral
weathering processes in soil. Increased air humidity decreased the nir and nosZ
gene abundance in the rhizosphere bacterial community. The potential contribution
of the denitrification to the N2O emission was not affected by the elevated air
humidity in birch stand soil. In addition, the study revealed a strong link
between the bacterial community structure, abundance of denitrification related
genes, and birch absorptive root morphology in the ecosystem system adaptation to
elevated air humidity.
PMID- 28421054
TI - Isolation and Characterization of Dehalobacter sp. Strain TeCB1 Including
Identification of TcbA: A Novel Tetra- and Trichlorobenzene Reductive
Dehalogenase.
AB - Dehalobacter sp. strain TeCB1 was isolated from groundwater near Sydney,
Australia, that is polluted with a range of organochlorines. The isolated strain
is able to grow by reductive dechlorination of 1,2,4,5-tetrachlorobenzene to 1,3-
and 1,4-dichlorobenzene with 1,2,4-trichlorobenzene being the intermediate
daughter product. Transient production of 1,2-dichlorobenzene was detected with
subsequent conversion to monochlorobenzene. The dehalogenation capability of
strain TeCB1 to respire 23 alternative organochlorines was examined and shown to
be limited to the use of 1,2,4,5-tetrachlorobenzene and 1,2,4-trichlorobenzene.
Growth on 1,2,4-trichlorobenzene resulted in the production of predominantly 1,3-
and 1,4-dichlorobenzene. The inability of strain TeCB1 to grow on 1,2
dichlorobenzene indicated that the production of monochlorobenzene during growth
on 1,2,4,5-tetarchlorobezene was cometabolic. The annotated genome of strain
TeCB1 contained only one detectable 16S rRNA gene copy and genes for 23 full
length and one truncated Reductive Dehalogenase (RDase) homologs, five unique to
strain TeCB1. Identification and functional characterization of the 1,2,4,5
tetrachlorobenzene and 1,2,4-trichlorobenzene RDase (TcbA) was achieved using
native-PAGE coupled with liquid chromatography tandem mass spectrometry.
Interestingly, TcbA showed higher amino acid identity with tetrachloroethene
reductases PceA (95% identity) from Dehalobacter restrictus PER-K23 and
Desulfitobacterium hafniense Y51 than with the only other chlorinated benzene
reductase [i.e., CbrA (30% identity)] functionally characterized to date.
PMID- 28421055
TI - Editorial: Genetics, Genomics and -Omics of Thermophiles.
PMID- 28421056
TI - High Prevalence of Colistin Resistance and mcr-1 Gene in Escherichia coli
Isolated from Food Animals in China.
AB - The objective of this study was to determine the minimal inhibitory concentration
of colistin for Escherichia coli from food animals and the possible underlying
colistin resistance mechanisms. During 2007-2014, 4,438 E. coli isolates of food
animal origins were collected. The susceptibility of colistin was tested by the
agar dilution method. Mutations in pmrA, pmrB, and mgrB and the presence of mcr-1
gene were determined by PCR and DNA sequencing. Complementation experiments were
carried out to evaluate the contribution of the mutations to colistin resistance.
There was a high frequency of colistin resistance in E. coli from pigs on farm
(24.1%) and at slaughter (24.3%) in 2013-2014, followed by chickens on farm
(14.0%) and at slaughter (9.5%). The resistance frequency of E. coli in cow
isolates was the lowest (0.9%). MIC distribution for colistin showed that most
isolates (75.2%) were distributed at 0.25 mg/L-0.5 mg/L, followed by 4 mg/L-8
mg/L (16.8%). Compared with the isolates from pigs and chickens recovered during
2013-2014, E. coli isolates collected during 2007-2008 (5.5%) and 2010-2011
(12.4%) showed significantly lower frequency of colistin resistance (P < 0.05).
DNA sequencing and complementation experiments failed to detect any insertion
inactivation or mutation in pmrA, pmrB, and mgrB associated with colistin
resistance. However, 91.0% colistin-resistant isolates were positive for mcr-1.
The high frequency of colistin resistance and mcr-1 gene among E. coli isolates
from food animals in China urged the need to minimize potential risks of colistin
resistance development and the spread of mcr-1 gene.
PMID- 28421058
TI - Antimicrobial Compounds Produced by Vaginal Lactobacillus crispatus Are Able to
Strongly Inhibit Candida albicans Growth, Hyphal Formation and Regulate Virulence
related Gene Expressions.
AB - The female vaginal environment contains diverse microorganisms, and their
interactions play significant roles in health and disease. Lactobacillus species
are the predominant vaginal microorganisms in healthy women and relevant as a
barrier to defense against pathogens, including Candida albicans. The yeast-to
hyphae transition is believed to be a determinant of C. albicans pathogenesis. In
this study, we investigated the effects of vaginal isolates of L. crispatus
(seven strains), L. gasseri (six strains), and L. jensenii (five strains) on
growth, hyphal formation and virulence-related genes expression of C. albicans
ATCC 10231. We found that the L. crispatus showed the most significant
antimicrobial activities in microplate-based liquid medium assay (P < 0.05). All
seven cell-free supernatants (CFS) from L. crispatus strains reduced the growth
of C. albicans by >60%. The effects might be due to their productions of some
secretory antimicrobial compounds in addition to H2O2 and organic acids.
Furthermore, each of the CFS of Lactobacillus strains was found to significantly
suppress the yeast-to-hyphae transition of C. albicans under hyphae-inducing
conditions (RPMI 1640 medium supplemented with 10% fetal bovine serum). The
hyphae inhibition rates of C. albicans treated by CFS from L. crispatus, L.
gasseri, and L. jensenii were 88.3 +/- 3.02%, 84.9 +/- 6.0%, and 81.9 +/- 6.2%,
respectively. Moreover, the expression of hyphae-specific genes (ALS3, HWP1,
ECE1, EAP1, and SAP5) and transcriptional regulatory genes (EFG1, TEC1, and NRG1)
were analyzed using quantitative real-time PCR. The results demonstrated that L.
crispatus CFS significantly down-regulated the expression of hyphae-specific
genes ALS3 (0.140-fold)), HWP1 (0.075-fold), and ECE1 (0.045-fold), while up
regulated the expression of the negative transcriptional regulator gene NRG1 with
1.911-fold. The antimicrobial compounds from L. crispatus B145 against Candida
growth were heat stable and protease resistance, but those against hyphal
formation were partially sensitive to the same treatments. Our novel findings
suggest that L. crispatus, a dominant Lactobacillus species associated with a
healthy vagina, could strongly inhibit C. albicans growth and hyphal formation.
L. crispatus might repress the expression of hyphae-specific genes (ALS3, HWP1,
and ECE1) in a NRG1-dependent manner. Besides, L. crispatus B145 is highly
worthwhile for probiotic investigation.
PMID- 28421057
TI - Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic
Fibers and Probiotics: A Review.
AB - In the present world scenario, obesity has almost attained the level of a
pandemic and is progressing at a rapid rate. This disease is the mother of all
other metabolic disorders, which apart from placing an added financial burden on
the concerned patient also has a negative impact on his/her well-being and health
in the society. Among the various plausible factors for the development of
obesity, the role of gut microbiota is very crucial. In general, the gut of an
individual is inhabited by trillions of microbes that play a significant role in
host energy homeostasis by their symbiotic interactions. Dysbiosis in gut
microbiota causes disequilibrium in energy homeostasis that ultimately leads to
obesity. Numerous mechanisms have been reported by which gut microbiota induces
obesity in experimental models. However, which microbial community is directly
linked to obesity is still unknown due to the complex nature of gut microbiota.
Prebiotics and probiotics are the safer and effective dietary substances
available, which can therapeutically alter the gut microbiota of the host. In
this review, an effort was made to discuss the current mechanisms through which
gut microbiota interacts with host energy metabolism in the context of obesity.
Further, the therapeutic approaches (prebiotics/probiotics) that helped in
positively altering the gut microbiota were discussed by taking experimental
evidence from animal and human studies. In the closing statement, the challenges
and future tasks within the field were discussed.
PMID- 28421059
TI - Phages in the Human Body.
AB - Bacteriophages, viruses that infect bacteria, have re-emerged as powerful
regulators of bacterial populations in natural ecosystems. Phages invade the
human body, just as they do other natural environments, to such an extent that
they are the most numerous group in the human virome. This was only revealed in
recent metagenomic studies, despite the fact that the presence of phages in the
human body was reported decades ago. The influence of the presence of phages in
humans has yet to be evaluated; but as in marine environments, a clear role in
the regulation of bacterial populations could be envisaged, that might have an
impact on human health. Moreover, phages are excellent vehicles of genetic
transfer, and they contribute to the evolution of bacterial cells in the human
body by spreading and acquiring DNA horizontally. The abundance of phages in the
human body does not pass unnoticed and the immune system reacts to them, although
it is not clear to what extent. Finally, the presence of phages in human samples,
which most of the time is not considered, can influence and bias microbiological
and molecular results; and, in view of the evidences, some studies suggest that
more attention needs to be paid to their interference.
PMID- 28421060
TI - The Heme Metabolite Carbon Monoxide Facilitates KSHV Infection by Inhibiting TLR4
Signaling in Endothelial Cells.
AB - Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS)
and certain rare B cell lymphoproliferative disorders. KSHV infection of
endothelial cells (EC) in vitro increases expression of the inducible host
encoded enzyme heme oxygenase-1 (HO-1), which is also strongly expressed in KS
tumors. HO-1 catalyzes the rate-limiting step in the conversion of heme into
iron, biliverdin and the gasotransmitter carbon monoxide (CO), all of which share
anti-apoptotic, anti-inflammatory, pro-survival, and tumorigenic activities. Our
previous work has shown that HO-1 expression in KSHV-infected EC is characterized
by a rapid yet transient induction at early times post-infection, followed by a
sustained upregulation co-incident with establishment of viral latency. These two
phases of expression are independently regulated, suggesting distinct roles for
HO-1 in the virus life cycle. Here, we investigated the role of HO-1 during acute
infection, prior to the onset of viral gene expression. The early infection phase
involves a series of events that culminate in delivery of the viral genome to the
nucleus. Primary infection also leads to activation of host innate immune
effectors, including the pattern recognition receptor TLR4, to induce an
antiviral response. It has been shown that TLR4-deficient EC are more susceptible
to KSHV infection than wild-type controls, suggesting an important inhibitory
role for TLR4 in the KSHV life cycle. TLR4 signaling is in turn subject to
regulation by several virus-encoded immune evasion factors. In this report we
identify HO-1 as a host protein co-opted by KSHV as part of a rapid immune
evasion strategy. Specifically, we show that early HO-1 induction by KSHV results
in increased levels of endogenous CO, which functions as a TLR4 signaling
inhibitor. In addition, we show that CO-mediated inhibition of TLR4 signaling
leads to reduced expression of TLR4-induced antiviral genes, thus dampening the
host antiviral response and facilitating KSHV infection. Conversely, inhibition
of HO-1 activity decreases intracellular CO, enhances the host antiviral response
and inhibits KSHV infection. In conclusion, this study identifies HO-1 as a novel
innate immune evasion factor in the context of KSHV infection and supports HO-1
inhibition as a viable therapeutic strategy for KS.
PMID- 28421061
TI - Comparative Analysis of the Gut Microbial Communities in Forest and Alpine Musk
Deer Using High-Throughput Sequencing.
AB - The gut ecosystem is characterized by dynamic and reciprocal interactions between
the host and bacteria. Although characterizing microbiota for herbivores has
become recognized as important tool for gauging species health, no study to date
has investigated the bacterial communities and evaluated the age-related
bacterial dynamics of musk deer. Moreover, gastrointestinal diseases have been
hypothesized to be a limiting factor of population growth in captive musk deer.
Here, high-throughput sequencing of the bacterial 16S rRNA gene was used to
profile the fecal bacterial communities in juvenile and adult alpine and forest
musk deer. The two musk deer species harbored similar bacterial communities at
the phylum level, whereas the key genera for the two species were distinct. The
bacterial communities were dominated by Firmicutes and Bacteroidetes, with the
bacterial diversity being higher in forest musk deer. The Firmicutes to
Bacteroidetes ratio also increased from juvenile to adult, while the bacterial
diversity, within-group and between-group similarity, all increased with age.
This work serves as the first sequence-based analysis of variation in bacterial
communities within and between musk deer species, and demonstrates how the gut
microbial community dynamics vary among closely related species and shift with
age. As gastrointestinal diseases have been observed in captive populations, this
study provides valuable data that might benefit captive management and future
reintroduction programs.
PMID- 28421062
TI - Identification of Rare PB2-D701N Mutation from a Patient with Severe Influenza:
Contribution of the PB2-D701N Mutation to the Pathogenicity of Human Influenza.
AB - Several amino acid changes have been previously implicated in adaptation of avian
influenza viruses to human hosts, among them the D701N change in the PB2
polymerase subunit that also is the main determinant of avian virus pathogenesis
in animal models. However, previous studies using recombinant viruses did not
provide conclusive information of the contribution of this PB2 residue to
pathogenicity in human influenza virus strains. We identified this mutation in an
A(H1N1)pdm09-like human influenza virus isolated from an infected patient with
pneumonia and acute respiratory failure, admitted to the intensive care unit. An
exhaustive search has revealed PB2-D701 as a highly conserved position in all
available H1N1 human virus sequences in NCBI database, showing a very low
prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with
severe or fatal outcome in those scarce cases with known disease outcome of the
infection. In these patients, the residue PB2-701N may contribute to
pathogenicity as it was previously reported in humans infected with avian
viruses. This study helps to clarify a debate that has arisen regarding the role
of PB2-D701N in human influenza virus pathogenicity.
PMID- 28421063
TI - Editorial: Drug Development for Parasite-Induced Diarrheal Diseases.
PMID- 28421065
TI - Zika Virus Infection during Pregnancy and Congenital Abnormalities.
AB - The presence of the Zika virus (ZIKV) infection has gone ahead to be a threat to
people based on its adverse impacts. More specifically, the pregnant women have
been discouraged from traveling to the areas affected by the ZIKV because of the
likelihood of the virus causing congenital abnormalities especially the
microcephaly. The pregnant women probably attracted the virus during their first
trimester while visiting ZIKV affected territories. Although the ZIKV infected
cases have reduced in some parts of countries, the global risk assessment has not
been changed. The virus continues to spread geographically to areas where
competent vectors are present. At present, there is still no treatment of ZIKV
related illness, especially microcephaly.
PMID- 28421064
TI - Current Perspectives on Viable but Non-culturable State in Foodborne Pathogens.
AB - The viable but non-culturable (VBNC) state, a unique state in which a number of
bacteria respond to adverse circumstances, was first discovered in 1982.
Unfortunately, it has been reported that many foodborne pathogens can be induced
to enter the VBNC state by the limiting environmental conditions during food
processing and preservation, such as extreme temperatures, drying, irradiation,
pulsed electric field, and high pressure stress, as well as the addition of
preservatives and disinfectants. After entering the VBNC state, foodborne
pathogens will introduce a serious crisis to food safety and public health
because they cannot be detected using conventional plate counting techniques.
This review provides an overview of the various features of the VBNC state,
including the biological characteristics, induction and resuscitation factors,
formation and resuscitation mechanisms, detection methods, and relationship to
food safety.
PMID- 28421066
TI - Unveiling the Hybrid Genome Structure of Escherichia coli RR1 (HB101 RecA+).
AB - There have been extensive genome sequencing studies for Escherichia coli strains,
particularly for pathogenic isolates, because fast determination of pathogenic
potential and/or drug resistance and their propagation routes is crucial. For
laboratory E. coli strains, however, genome sequence information is limited
except for several well-known strains. We determined the complete genome sequence
of laboratory E. coli strain RR1 (HB101 RecA+), which has long been used as a
general cloning host. A hybrid genome sequence of K-12 MG1655 and B BL21(DE3) was
constructed based on the initial mapping of Illumina HiSeq reads to each
reference, and iterative rounds of read mapping, variant detection, and consensus
extraction were carried out. Finally, PCR and Sanger sequencing-based finishing
were applied to resolve non-single nucleotide variant regions with aberrant read
depths and breakpoints, most of them resulting from prophages and insertion
sequence transpositions that are not present in the reference genome sequence. We
found that 96.9% of the RR1 genome is derived from K-12, and identified exact
crossover junctions between K-12 and B genomic fragments. However, because RR1
has experienced a series of genetic manipulations since branching from the common
ancestor, it has a set of mutations different from those found in K-12 MG1655. As
well as identifying all known genotypes of RR1 on the basis of genomic context,
we found novel mutations. Our results extend current knowledge of the genotype of
RR1 and its relatives, and provide insights into the pedigree, genomic
background, and physiology of common laboratory strains.
PMID- 28421067
TI - C-C Motif Chemokine Ligand 2 (CCL2) Mediates Acute Lung Injury Induced by Lethal
Influenza H7N9 Virus.
AB - An avian-origin influenza A (H7N9) virus was a cause for concern in China in the
spring of 2013. Most H7N9 infections resulted in acute respiratory distress
syndrome (ARDS), which is a severe form of acute lung injury (ALI) that
contributes to morbidity and mortality. In this study, we induced viral ALI by
infecting wild-type and CCL2-deficient mice with influenza H7N9 virus. The
results suggested a close association between C-C motif chemokine ligand 2 (CCL2)
expressions and ALI induced by a lethal H7N9 virus strain (A/Hebei/01/2013).
Elevated CCL2 levels were also detected in confirmed human cases of H7N9 and the
bronchoalveolar lavage fluid (BALF) of H7N9-infected mice. Moreover, CCL2 was
overexpressed in the lung tissue of infected mice. More importantly, CCL2
deficiency ameliorated H7N9-induced ALI in mice as determined by weight loss,
survival rate, the wet:dry ratio of the lung, and pathology. Taken together, our
findings demonstrate that CCL2 is essential for H7N9 virus infection and thus
that it is a potential therapeutic target for influenza.
PMID- 28421068
TI - Model-Driven Experimentation: A New Approach to Understand Mechanisms of Tertiary
Lymphoid Tissue Formation, Function, and Therapeutic Resolution.
AB - The molecular and cellular processes driving the formation of secondary lymphoid
tissues have been extensively studied using a combination of mouse knockouts,
lineage-specific reporter mice, gene expression analysis, immunohistochemistry,
and flow cytometry. However, the mechanisms driving the formation and function of
tertiary lymphoid tissue (TLT) experimental techniques have proven to be more
enigmatic and controversial due to differences between experimental models and
human disease pathology. Systems-based approaches including data-driven
biological network analysis (gene interaction network, metabolic pathway network,
cell-cell signaling, and cascade networks) and mechanistic modeling afford a
novel perspective from which to understand TLT formation and identify mechanisms
that may lead to the resolution of tissue pathology. In this perspective, we make
the case for applying model-driven experimentation using two case studies, which
combined simulations with experiments to identify mechanisms driving lymphoid
tissue formation and function, and then discuss potential applications of this
experimental paradigm to identify novel therapeutic targets for TLT pathology.
PMID- 28421069
TI - Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't
Forget the Fuel.
AB - T-cells play a critical role in tumor immunity. Indeed, the presence of tumor
infiltrating lymphocytes is a predictor of favorable patient prognosis for many
indications and is a requirement for responsiveness to immune checkpoint blockade
therapy targeting programmed cell death 1. For tumors lacking immune infiltrate,
or for which antigen processing and/or presentation has been downregulated, a
promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell
therapy. CARs are hybrid receptors that link the tumor antigen specificity and
affinity of an antibody-derived single-chain variable fragment with signaling
endodomains associated with T-cell activation. CAR therapy targeting CD19 has
yielded extraordinary clinical responses against some hematological tumors. Solid
tumors, however, remain an important challenge to CAR T-cells due to issues of
homing, tumor vasculature and stromal barriers, and a range of obstacles in the
tumor bed. Protumoral immune infiltrate including T regulatory cells and myeloid
derived suppressor cells have been well characterized for their ability to
upregulate inhibitory receptors and molecules that hinder effector T-cells. A
critical role for metabolic barriers in the tumor microenvironment (TME) is
emerging. High glucose consumption and competition for key amino acids by tumor
cells can leave T-cells with insufficient energy and biosynthetic precursors to
support activities such as cytokine secretion and lead to a phenotypic state of
anergy or exhaustion. CAR T-cell expansion protocols that promote a less
differentiated phenotype, combined with optimal receptor design and coengineering
strategies, along with immunomodulatory therapies that also promote endogenous
immunity, offer great promise in surmounting immunometabolic barriers in the TME
and curing solid tumors.
PMID- 28421070
TI - Interplay of Regulatory T Cell and Th17 Cells during Infectious Diseases in
Humans and Animals.
AB - It is now clear that the outcome of an inflammatory process caused by infections
depends on the balance of responses by several components of the immune system.
Of particular relevance is the interplay between regulatory T cells (Tregs) and
CD4+ T cells that produce IL-17 (Th17 cells) during immunoinflammatory events. In
addition to discussing studies done in mice to highlight some unresolved issues
in the biology of these cells, we emphasize the need to include outbred animals
and humans in analyses. Achieving a balance between Treg and Th17 cells responses
represents a powerful approach to control events during immunity and
immunopathology.
PMID- 28421071
TI - Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations,
and Genotype/Phenotype Correlations.
AB - Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of
diseases caused by mutations of genes encoding proteins, which play a pivotal
role in the regulation of the inflammatory response. In the pathogenesis of AIDs,
the role of the genetic background is triggered by environmental factors through
the modulation of the innate immune system. Monogenic AIDs are characterized by
Mendelian inheritance and are caused by highly penetrant genetic variants in
single genes. During the last years, remarkable progress has been made in the
identification of disease-associated genes by using new technologies, such as
next-generation sequencing, which has allowed the genetic characterization in
undiagnosed patients and in sporadic cases by means of targeted resequencing of a
gene panel and whole exome sequencing. In this review, we delineate the genetics
of the monogenic AIDs, report the role of the most common gene mutations, and
describe the evidences of the most sound genotype/phenotype correlations in AID.
PMID- 28421072
TI - Dysregulated IL-1beta Secretion in Autoinflammatory Diseases: A Matter of Stress?
AB - Infectious and sterile inflammation is induced by activation of innate immune
cells. Triggering of toll-like receptors by pathogen-associated molecular pattern
or damage-associated molecular pattern (PAMP or DAMP) molecules generates
reactive oxygen species that in turn induce production and activation of pro
inflammatory cytokines such as IL-1beta. Recent evidence indicates that cell
stress due to common events, like starvation, enhanced metabolic demand, cold or
heat, not only potentiates inflammation but may also directly trigger it in the
absence of PAMPs or DAMPs. Stress-mediated inflammation is also a common feature
of many hereditary disorders, due to the proteotoxic effects of mutant proteins.
We propose that harmful mutant proteins can induce dysregulated IL-1beta
production and inflammation through different pathways depending on the cell type
involved. When expressed in professional inflammatory cells, stress induced by
the mutant protein activates in a cell-autonomous way the onset of inflammation
and mediates its aberrant development, resulting in the explosive responses that
hallmark autoinflammatory diseases. When expressed in non-immune cells, the
mutant protein may cause the release of transcellular stress signals that trigger
and propagate inflammation.
PMID- 28421073
TI - What Fuels Natural Killers? Metabolism and NK Cell Responses.
AB - There is a growing appreciation that cellular metabolism is important in
determining the course of lymphocyte responses. Additionally, changes in
metabolic processes have been linked to dysfunctional lymphocyte functions in a
number of different diseases. While most early studies of metabolic regulation of
lymphocyte function focused on T lymphocytes, an understanding of how metabolic
pathways impact upon natural killer (NK) cell responses is now starting to
emerge. In this review article, we will discuss how cellular metabolism
influences lymphocyte function with a particular focus upon NK cells.
PMID- 28421074
TI - Immunometabolic Phenotype Alterations Associated with the Induction of Disease
Tolerance and Persistent Asymptomatic Infection of Salmonella in the Chicken
Intestine.
AB - The adaptation of Salmonella enterica to the eukaryotic host is a key process
that enables the bacterium to survive in a hostile environment. Salmonella have
evolved an intimate relationship with its host that extends to their cellular and
molecular levels. Colonization, invasion, and replication of the bacteria in an
appropriate host suggest that modification of host functions is central to
pathogenesis. Intuitively, this subversion of the cell must be a complex process,
since hosts are not inherently programmed to provide an environment conducive to
pathogens. Hosts have evolved countermeasures to pathogen invasion,
establishment, and replication through two types of defenses: resistance and
tolerance. Resistance functions to control pathogen invasion and reduce or
eliminate the invading pathogen. Research has primarily concentrated on
resistance mechanisms that are mediated by the immune system. On the other hand,
tolerance is mediated by different mechanisms that limit the damage caused by a
pathogen's growth without affecting or reducing pathogen numbers or loads. The
mechanisms of tolerance appear to be separated into those that protect host
tissues from the virulence factors of a pathogen and those that limit or reduce
the damage caused by the host immune and inflammatory responses to the pathogen.
Some pathogens, such as Salmonella, have evolved the capacity to survive the
initial robust immune response and persist. The persistent phase of a Salmonella
infection in the avian host usually involves a complex balance of protective
immunity and immunopathology. Salmonella is able to stay in the avian ceca for
months without triggering clinical signs. Chronic colonization of the intestinal
tract is an important aspect of persistent Salmonella infection because it
results in a silent propagation of bacteria in poultry stocks due to the
impossibility to isolate contaminated animals. Data from our lab promote the
hypothesis that Salmonella have evolved a unique survival strategy in poultry
that minimizes host defenses (disease resistance) during the initial infection
and then exploits and/or induces a dramatic immunometabolic reprogramming in the
cecum that alters the host defense to disease tolerance. Unfortunately, this
disease tolerance results in the ongoing human food safety dilemma.
PMID- 28421075
TI - Activation of Adhesion GPCR EMR2/ADGRE2 Induces Macrophage Differentiation and
Inflammatory Responses via Galpha16/Akt/MAPK/NF-kappaB Signaling Pathways.
AB - EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor
critically implicated in vibratory urticaria, a rare type of allergy caused by
vibration-induced mast cell activation. In addition, EMR2 is also highly
expressed by monocyte/macrophages and has been linked to neutrophil migration and
activation. Despite these findings, little is known of EMR2-mediated signaling
and its role in myeloid biology. In this report, we show that activation of EMR2
via a receptor-specific monoclonal antibody promotes the differentiation of human
THP-1 monocytic cell line and induces the expression of pro-inflammatory
mediators, including IL-8, TNF-alpha, and MMP-9. Using specific signaling
inhibitors and siRNA knockdowns, biochemical and functional analyses reveal that
the EMR2-mediated signaling is initiated by Galpha16, followed by the subsequent
activation of Akt, extracellular signal-regulated kinase, c-Jun N-terminal
kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells. Our
results demonstrate a functional role for EMR2 in the differentiation and
inflammatory activation of human monocytic cells and provide potential targets
for myeloid cell-mediated inflammatory disorders.
PMID- 28421076
TI - Broad-Based CD4+ T Cell Responses to Influenza A Virus in a Healthy Individual
Who Lacks Typical Immunodominance Hierarchy.
AB - Influenza A virus (IAV) infection is a significant cause of morbidity and
mortality worldwide. CD4+ T cell responses have been shown to be important for
influenza protection in mouse models and in human volunteers. IAV antigen
specific CD4+ T cell responses were found to focus on matrix 1 (M1) and
nucleoprotein (NP) at the protein antigen level. At the epitope level, only
several epitopes within M1 and NP were recognized by CD4+ T cells. And the
epitope-specific CD4+ T cell responses showed a typical immunodominance hierarchy
in most of the healthy individuals studied. In this study, we reported one case
of atypical immunodominance hierarchy of CD4+ T cell responses to IAV. M1 and NP
were still the immunodominant targets of CD4+ T cell responses. However, CD4+ T
cell responses specific to 11 epitopes derived from M1 and NP were detected and
showed no significant immunodominance hierarchy. Such an atypical pattern is
likely determined by the individual's HLA alleles. These findings will help us
better understand the anti-IAV immunity as a whole and improve future vaccines
against IAV.
PMID- 28421077
TI - Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle
Exposure Is Size Specific.
AB - The application of nanotechnology in the health care setting has many potential
benefits; however, our understanding of the interactions between nanoparticles
and our immune system remains incomplete. Although many of the biological effects
of nanoparticles are negatively correlated with particle size, some are clearly
size specific and the mechanisms underlying these size-specific biological
effects remain unknown. Here, we examined the pro-inflammatory effects of silica
particles in THP-1 cells with respect to particle size; a large overall size
range with narrow intervals between particle diameters (particle diameter: 10,
30, 50, 70, 100, 300, and 1,000 nm) was used. Secretion of the pro-inflammatory
cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha induced by
exposure to the silica particles had a bell-shaped distribution, where the
maximal secretion was induced by silica nanoparticles with a diameter of 50 nm
and particles with smaller or larger diameters had progressively less effect. We
found that blockade of IL-1beta secretion markedly inhibited TNF-alpha secretion,
suggesting that IL-1beta is upstream of TNF-alpha in the inflammatory cascade
induced by exposure to silica particles, and that the induction of IL-1beta
secretion was dependent on both the NLRP3 inflammasome and on uptake of the
silica particles into the cells via endocytosis. However, a quantitative analysis
of silica particle uptake showed that IL-1beta secretion was not correlated with
the amount of silica particles taken up by the cells. Further investigation
revealed that the induction of IL-1beta secretion and uptake of silica
nanoparticles with diameters of 50 or 100 nm, but not of 10 or 1,000 nm, was
dependent on scavenger receptor (SR) A1. In addition, of the silica particles
examined, only those with a diameter of 50 nm induced strong IL-1beta secretion
via activation of Mer receptor tyrosine kinase, a signal mediator of SR A1.
Together, our results suggest that the SR A1-mediated pro-inflammatory response
is dependent on ligand size and that both SR A1-mediated endocytosis and receptor
mediated signaling are required to produce the maximal pro-inflammatory response
to exposure to silica particles.
PMID- 28421079
TI - Severe Sequelae to Mold-Related Illness as Demonstrated in Two Finnish Cohorts.
AB - The presence of toxic indoor molds with accompanying bacterial growth is clearly
detrimental to human health. The pathophysiological and toxicological effects of
toxins and structural components of molds and bacteria have been clarified in
experiments conducted in tissue culture and animals, and there is convincing
epidemiologic evidence; nonetheless their implications for human health are
either ignored or denied, at least in Finland. In this communication, we describe
two cohorts suffering severe sequelae to mold-related illness. One cohort is a
nine-member family with pets that moved into a new house, which soon proved to be
infested with pathogenic molds. The other cohort consists of 30 teachers and 50
students from a mold-infested school building. The first cohort experienced a
plethora of mucosal irritation, neurological, skin, allergic, and other symptoms,
with all family members ultimately developing a multiple chemical syndrome. In
the second cohort, we detected a greatly elevated prevalence of autoimmune
conditions and malignancies. We claim that mold-related illness exists in
multiple facets; if not simply a transient mucosal irritation or even an
increased risk of asthma onset or its exacerbation. We propose a scheme to
explain the natural course of the mold-related illness. We recommend that future
studies should combine data from, e.g., cancer, autoimmune, and endocrine
disorder registers and neurological and mental health or neuropsychological
registers with mold-exposed individuals being monitored for prolonged follow-up
times.
PMID- 28421080
TI - B Cell Functions Can Be Modulated by Antimicrobial Peptides in Rainbow Trout
Oncorhynchus mykiss: Novel Insights into the Innate Nature of B Cells in Fish.
AB - B cells in fish were recently proven to have potent innate immune activities like
macrophages. This inspired us to further explore the innate nature of B cells in
fish. Moreover, antimicrobial peptides (AMPs) are representative molecules of
innate immunity, and they can modulate the functions of macrophages. These make
fish an appropriate model to study the interactions between B cells and AMPs.
Interestingly, the results in this study revealed that the IgM+ and IgT+ B cells
of rainbow trout could express multiple AMP genes, including four cathelicidin
genes and one beta-defensin gene. The expression levels of the cathelicidin genes
were obviously higher than that of the beta-defensin gene. Further studies
revealed that intracellular, extracellular, in vitro, and in vivo stimulations
could significantly increase the expression of the cathelicidin genes in trout
IgM+ and IgT+ B cells but not the expression of the beta-defensin gene,
indicating that cathelicidin peptides are the main innate immune effectors of
trout B cells. More interestingly, we found that cathelicidin peptides could
significantly enhance the phagocytic, intracellular bactericidal, and reactive
oxygen species activities of trout IgM+ and IgT+ B cells, a phenomenon previously
reported only in macrophages, and these activities might also be mediated by the
P2X7 receptor. These results collectively suggest that B cells play multiple
roles in the innate immunity of fish, and they provide new evidence for
understanding the close relationship between B cells and macrophages in
vertebrates.
PMID- 28421078
TI - Genetic Association of Hematopoietic Stem Cell Transplantation Outcome beyond
Histocompatibility Genes.
AB - The outcome of hematopoietic stem cell transplantation (HSCT) is controlled by
genetic factors among which the leukocyte antigen human leukocyte antigen (HLA)
matching is most important. In addition, minor histocompatibility antigens and
non-HLA gene polymorphisms in genes controlling immune responses are known to
contribute to the risks associated with HSCT. Besides single-nucleotide
polymorphisms (SNPs) in protein coding genes, SNPs in regulatory elements such as
microRNAs (miRNAs) contribute to these genetic risks. However, genetic risks
require for their realization the expression of the respective gene or miRNA.
Thus, gene and miRNA expression studies may help to identify genes and SNPs that
indeed affect the outcome of HSCT. In this review, we summarize gene expression
profiling studies that were performed in recent years in both patients and animal
models to identify genes regulated during HSCT. We discuss SNP-mRNA-miRNA
regulatory networks and their contribution to the risks associated with HSCT in
specific examples, including forkheadbox protein 3 and regulatory T cells, the
role of the miR-155 and miR-146a regulatory network for graft-versus-host
disease, and the function of MICA and its receptor NKG2D for the outcome of HSCT.
These examples demonstrate how SNPs affect expression or function of proteins
that modulate the alloimmune response and influence the outcome of HSCT. Specific
miRNAs targeting these genes and directly affecting expression of mRNAs are
identified. It might be valuable in the future to determine SNPs and to analyze
miRNA and mRNA expression in parallel in cohorts of HSCT patients to further
elucidate genetic risks of HSCT.
PMID- 28421081
TI - Mechanistic Insight into Salt Tolerance of Acacia auriculiformis: The Importance
of Ion Selectivity, Osmoprotection, Tissue Tolerance, and Na+ Exclusion.
AB - Salinity, one of the major environmental constraints, threatens soil health and
consequently agricultural productivity worldwide. Acacia auriculiformis, being a
halophyte, offers diverse benefits against soil salinity; however, the defense
mechanisms underlying salt-tolerant capacity in A. auriculiformis are still
elusive. In this study, we aimed to elucidate mechanisms regulating the
adaptability of the multi-purpose perennial species A. auriculiformis to salt
stress. The growth, ion homeostasis, osmoprotection, tissue tolerance and Na+
exclusion, and anatomical adjustments of A. auriculiformis grown in varied doses
of seawater for 90 and 150 days were assessed. Results showed that diluted
seawater caused notable reductions in the level of growth-related parameters,
relative water content, stomatal conductance, photosynthetic pigments, proteins,
and carbohydrates in dose- and time-dependent manners. However, the percent
reduction of these parameters did not exceed 50% of those of control plants. Na+
contents in phyllodes and roots increased with increasing levels of salinity,
whereas K+ contents and K+/Na+ ratio decreased significantly in comparison with
control plants. A. auriculiformis retained more Na+ in the roots and maintained
higher levels of K+, Ca2+ and Mg2+, and K+/Na+ ratio in phyllodes than roots
through ion selective capacity. The contents of proline, total free amino acids,
total sugars and reducing sugars significantly accumulated together with the
levels of malondialdehyde and electrolyte leakage in the phyllodes, particularly
at day 150th of salt treatment. Anatomical investigations revealed various
anatomical changes in the tissues of phyllodes, stems and roots by salt stress,
such as increase in the size of spongy parenchyma of phyllodes, endodermal
thickness of stems and roots, and the diameter of root vascular bundle, relative
to control counterparts. Furthermore, the estimated values for Na+ exclusion and
tissue tolerance index suggested that A. auriculiformis efficiently adopted these
two mechanisms to address higher salinity levels. Our results conclude that the
adaptability of A. auriculiformis to salinity is closely associated with ion
selectivity, increased accumulation of osmoprotectants, efficient Na+ retention
in roots, anatomical adjustments, Na+ exclusion and tissue tolerance mechanisms.
PMID- 28421082
TI - Insights into the Structure, Function, and Ion-Mediated Signaling Pathways
Transduced by Plant Integrin-Linked Kinases.
AB - Kinases facilitate detection of extracellular signals and set in motion cellular
responses for plant adaptation and survival. Some of the energy utilized for
kinase signal processing is produced through the activity of ion transporters.
Additionally, the synergy between cellular ions and signal transduction
influences plant response to pathogens, and their growth and development. In
plants, the signaling elements that connect cell wall and membrane sensors with
ion homeostasis and transport-mediated processes are largely unknown. Current
research indicates that plant Integrin-Linked Kinases (ILKs), a subfamily Raf
like MAP2K Kinases, may have evolved to fulfill this role. In this review, we
explore new findings on plant ILKs placing a particular focus on the connection
between ILKs proteins unique structural features and ILKs functions. The ankyrin
repeat motifs and the kinase domains of ILKs in Arabidopsis and land plants
lineage, respectively, are analyzed and discussed as potential determinants of
ILKs' metal ion cofactor specificity and their enzymatic and interaction
activities. Further, ILKs regulation through gene expression, subcellular
localization, and ions and ion transporters is reviewed in the context of recent
studies. Finally, using evidence from literature and interactomics databanks, we
infer ILKs-dependent cellular pathways and highlight their potential in
transmitting multiple types of signals originating at the interface between the
cell wall and plasma membrane.
PMID- 28421083
TI - LTRtype, an Efficient Tool to Characterize Structurally Complex LTR
Retrotransposons and Nested Insertions on Genomes.
AB - The amplification and recombination of long terminal repeat (LTR)
retrotransposons have proven to determine the size, organization, function, and
evolution of most host genomes, especially very large plant genomes. However, the
limitation of tools for an efficient discovery of structural complexity of LTR
retrotransposons and the nested insertions is a great challenge to confront ever
growing amount of genomic sequences for many organisms. Here we developed a novel
software, called as LTRtype, to characterize different types of structurally
complex LTR retrotransposon elements as well as nested events. This system is
capable of rapidly scanning large-scale genomic sequences and appropriately
characterizing the five complex types of LTR retrotransposon elements. After
testing on the Arabidopsis thaliana genome, we found that this program is able to
properly annotate a large number of structurally complex elements as well as the
nested insertions. Thus, LTRtype can be employed as an automatic and efficient
tool that will help to reconstruct the evolutionary history of LTR
retrotransposons and better understand the evolution of host genomes. LTRtype is
publicly available at: http://www.plantkingdomgdb.com/LTRtype/index.html.
PMID- 28421084
TI - Characterization of the Heme Pocket Structure and Ligand Binding Kinetics of Non
symbiotic Hemoglobins from the Model Legume Lotus japonicus.
AB - Plant hemoglobins (Hbs) are found in nodules of legumes and actinorhizal plants
but also in non-symbiotic organs of monocots and dicots. Non-symbiotic Hbs
(nsHbs) have been classified into two phylogenetic groups. Class 1 nsHbs show an
extremely high O2 affinity and are induced by hypoxia and nitric oxide (NO),
whereas class 2 nsHbs have moderate O2 affinity and are induced by cold and
cytokinins. The functions of nsHbs are still unclear, but some of them rely on
the capacity of hemes to bind diatomic ligands and catalyze the NO dioxygenase
(NOD) reaction (oxyferrous Hb + NO -> ferric Hb + nitrate). Moreover, NO may
nitrosylate Cys residues of proteins. It is therefore important to determine the
ligand binding properties of the hemes and the role of Cys residues. Here, we
have addressed these issues with the two class 1 nsHbs (LjGlb1-1 and LjGlb1-2)
and the single class 2 nsHb (LjGlb2) of Lotus japonicus, which is a model legume
used to facilitate the transfer of genetic and biochemical information into
crops. We have employed carbon monoxide (CO) as a model ligand and resonance
Raman, laser flash photolysis, and stopped-flow spectroscopies to unveil major
differences in the heme environments and ligand binding kinetics of the three
proteins, which suggest non-redundant functions. In the deoxyferrous state,
LjGlb1-1 is partially hexacoordinate, whereas LjGlb1-2 shows complete
hexacoordination (behaving like class 2 nsHbs) and LjGlb2 is mostly
pentacoordinate (unlike other class 2 nsHbs). LjGlb1-1 binds CO very strongly by
stabilizing it through hydrogen bonding, but LjGlb1-2 and LjGlb2 show lower CO
stabilization. The changes in CO stabilization would explain the different
affinities of the three proteins for gaseous ligands. These affinities are
determined by the dissociation rates and follow the order LjGlb1-1 > LjGlb1-2 >
LjGlb2. Mutations LjGlb1-1 C78S and LjGlb1-2 C79S caused important alterations in
protein dynamics and stability, indicating a structural role of those Cys
residues, whereas mutation LjGlb1-1 C8S had a smaller effect. The three proteins
and their mutant derivatives exhibited similarly high rates of NO consumption,
which were due to NOD activity of the hemes and not to nitrosylation of Cys
residues.
PMID- 28421085
TI - Expression of Arabidopsis SHN1 in Indian Mulberry (Morus indica L.) Increases
Leaf Surface Wax Content and Reduces Post-harvest Water Loss.
AB - Mulberry (Morus species) leaf is the sole food for monophagous silkworms, Bombyx
mori L. Abiotic stresses such as drought, salinity, and high temperature,
significantly decrease mulberry productivity and post-harvest water loss from
leaves influence silkworm growth and cocoon yield. Leaf surface properties
regulate direct water loss through the cuticular layer. Leaf surface waxes,
contribute for cuticular resistance and protect mesophyll cells from desiccation.
In this study we attempted to overexpress AtSHN1, a transcription factor
associated with epicuticular wax biosynthesis to increase leaf surface wax load
in mulberry. Agrobacterium mediated in vitro transformation was carried out using
hypocotyl and cotyledonary explants of Indian mulberry (cv. M5). Mulberry
transgenic plants expressing AtSHN1 displayed dark green shiny appearance with
increased leaf surface wax content. Scanning electron microscopy (SEM) and gas
chromatograph-mass spectrometry (GC-MS) analysis showed change in pattern of
surface wax deposition and significant change in wax composition in AtSHN1
overexpressors. Increased wax content altered leaf surface properties as there
was significant difference in water droplet contact angle and diameter between
transgenic and wild type plants. The transgenic plants showed significant
improvement in leaf moisture retention capacity even 5 h after harvest and there
was slow degradation of total buffer soluble protein in detached leaves compared
to wild type. Silkworm bioassay did not indicate any undesirable effects on
larval growth and cocoon yield. This study demonstrated that expression of
AtSHN1, can increase surface wax load and reduce the post-harvest water loss in
mulberry.
PMID- 28421086
TI - Association Analysis of Markers Derived from Starch Biosynthesis Related Genes
with Starch Physicochemical Properties in the USDA Rice Mini-Core Collection.
AB - Rice eating and cooking quality is largely determined by starch physicochemical
properties. The diverse accessions in the USDA rice mini-core collection (URMC)
facilitate extensive association analysis of starch physicochemical properties
with molecular markers specific to starch biosynthesis related genes. To identify
significant trait-marker associations that can be utilized in rice breeding
programs for improved starch quality, we conducted two association analyses
between 26 molecular markers derived from starch biosynthesis related genes and
18 parameters measured of starch physicochemical properties in two sets of the
mini-core accessions successfully grown in two environments in China. Many
significant trait-marker associations (P < 0.001) were detected in both
association analyses. Five markers of Waxy gene, including the (CT)n repeats, the
G/T SNP of intron 1, the 23 bp sequence duplication (InDel) of exon 2, the A/C
SNP of exon 6, and the C/T SNP of exon 10, were found to be primarily associated
with starch traits related to apparent amylose content (AAC), and two markers
targeting the 4,329-4,330 bp GC/TT SNPs and 4,198 bp G/A SNP of SSIIa gene were
mainly associated with traits related to gelatinization temperature (GT). Two new
haplotypes were found in the mini-core collection based on the combinations of
the 23 bp InDel and three SNPs (G/T of intron 1, A/C of exon 6, and C/T of exon
10) of Waxy gene. Furthermore, our analyses indicated that the (CT)n
polymorphisms of Waxy gene had a non-negligible effect on AAC related traits, as
evidenced by significant variation in AAC related traits among rice accessions
with the same Waxy SNPs but different (CT) n repeats. As the five Waxy markers
and the two SSIIa markers showed consistent major effects on starch quality
traits across studies, these markers should have priority for utilization in
marker-assisted breeding.
PMID- 28421088
TI - Non-host Resistance: DNA Damage Is Associated with SA Signaling for Induction of
PR Genes and Contributes to the Growth Suppression of a Pea Pathogen on Pea
Endocarp Tissue.
AB - Salicylic acid (SA) has been reported to induce plant defense responses. The
transcriptions of defense genes that are responsible for a given plant's
resistance to an array of plant pathogens are activated in a process called non
host resistance. Biotic signals capable of carrying out the activation of
pathogenesis-related (PR) genes in pea tissue include fungal DNase and chitosan,
two components released from Fusarium solani spores that are known to target host
DNA. Recent reports indicate that SA also has a physical affinity for DNA. Here,
we report that SA-induced reactive oxygen species release results in fragment
alterations in pea nuclear DNA and cytologically detectable diameter and
structural changes in the pea host nuclei. Additionally, we examine the
subsequent SA-related increase of resistance to the true pea pathogen F. solani
f.sp. pisi and the accumulation of the phytoalexin pisatin. This is the first
report showing that SA-induced PR gene activation may be attributed to the host
pea genomic DNA damage and that at certain concentrations, SA can be temporally
associated with subsequent increases in the defense response of this legume.
PMID- 28421089
TI - Using a Structural Root System Model to Evaluate and Improve the Accuracy of Root
Image Analysis Pipelines.
AB - Root system analysis is a complex task, often performed with fully automated
image analysis pipelines. However, the outcome is rarely verified by ground-truth
data, which might lead to underestimated biases. We have used a root model,
ArchiSimple, to create a large and diverse library of ground-truth root system
images (10,000). For each image, three levels of noise were created. This library
was used to evaluate the accuracy and usefulness of several image descriptors
classically used in root image analysis softwares. Our analysis highlighted that
the accuracy of the different traits is strongly dependent on the quality of the
images and the type, size, and complexity of the root systems analyzed. Our study
also demonstrated that machine learning algorithms can be trained on a synthetic
library to improve the estimation of several root system traits. Overall, our
analysis is a call to caution when using automatic root image analysis tools. If
a thorough calibration is not performed on the dataset of interest, unexpected
errors might arise, especially for large and complex root images. To facilitate
such calibration, both the image library and the different codes used in the
study have been made available to the community.
PMID- 28421087
TI - Evolutionary Analysis of the LAFL Genes Involved in the Land Plant Seed
Maturation Program.
AB - Seeds are one of the most significant innovations in the land plant lineage,
critical to the diversification and adaptation of plants to terrestrial
environments. From perspective of seed evo-devo, the most crucial developmental
stage in this innovation is seed maturation, which includes accumulation of
storage reserves, acquisition of desiccation tolerance, and induction of
dormancy. Based on previous studies of seed development in the model plant
Arabidopsis thaliana, seed maturation is mainly controlled by the LAFL regulatory
network, which includes LEAFY COTYLEDON1 (LEC1) and LEC1-LIKE (L1L) of the NF-YB
gene family, and ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2
(LEAFY COTYLEDON2) of the B3-AFL gene family. In the present study, molecular
evolution of these LAFL genes was analyzed, using representative species from
across the major plant lineages. Additionally, to elucidate the molecular
mechanisms of the seed maturation program, co-expression pattern analyses of LAFL
genes were conducted across vascular plants. The results show that the origin of
AFL gene family dates back to a common ancestor of bryophytes and vascular
plants, while LEC1-type genes are only found in vascular plants. LAFL genes of
vascular plants likely specify their co-expression in two different developmental
phrases, spore and seed maturation, respectively, and expression patterns vary
slightly across the major vascular plants lineages. All the information presented
in this study will provide insights into the origin and diversification of seed
plants.
PMID- 28421090
TI - Comparative Genomics and Phylogenomics of East Asian Tulips (Amana, Liliaceae).
AB - The genus Amana Honda (Liliaceae), when it is treated as separate from Tulipa,
comprises six perennial herbaceous species that are restricted to China, Japan
and the Korean Peninsula. Although all six Amana species have important medicinal
and horticultural uses, studies focused on species identification and molecular
phylogenetics are few. Here we report the nucleotide sequences of six complete
Amana chloroplast (cp) genomes. The cp genomes of Amana range from 150,613 bp to
151,136 bp in length, all including a pair of inverted repeats (25,629-25,859 bp)
separated by the large single-copy (81,482-82,218 bp) and small single-copy
(17,366-17,465 bp) regions. Each cp genome equivalently contains 112 unique genes
consisting of 30 transfer RNA genes, four ribosomal RNA genes, and 78 protein
coding genes. Gene content, gene order, AT content, and IR/SC boundary structure
are nearly identical among all Amana cp genomes. However, the relative
contraction and expansion of the IR/SC borders among the six Amana cp genomes
results in length variation among them. Simple sequence repeat (SSR) analyses of
these Amana cp genomes indicate that the richest SSRs are A/T mononucleotides.
The number of repeats among the six Amana species varies from 54 (A. anhuiensis)
to 69 (Amana kuocangshanica) with palindromic (28-35) and forward repeats (23-30)
as the most common types. Phylogenomic analyses based on these complete cp
genomes and 74 common protein-coding genes strongly support the monophyly of the
genus, and a sister relationship between Amana and Erythronium, rather than a
shared common ancestor with Tulipa. Nine DNA markers (rps15-ycf1, accD-psaI, petA
psbJ, rpl32-trnL, atpH-atpI, petD-rpoA, trnS-trnG, psbM-trnD, and ycf4-cemA) with
number of variable sites greater than 0.9% were identified, and these may be
useful for future population genetic and phylogeographic studies of Amana
species.
PMID- 28421091
TI - Oil Palm and Rubber Tree Water Use Patterns: Effects of Topography and Flooding.
AB - Oil palm and rubber plantations extend over large areas and encompass
heterogeneous site conditions. In periods of high rainfall, plants in valleys and
at riparian sites are more prone to flooding than plants at elevated topographic
positions. We asked to what extent topographic position and flooding affect oil
palm and rubber tree water use patterns and thereby influence spatial and
temporal heterogeneity of transpiration. In an undulating terrain in the lowlands
of Jambi, Indonesia, plantations of the two species were studied in plot pairs
consisting of upland and adjacent valley plots. All upland plots were non
flooded, whereas the corresponding valley plots included non-flooded, long-term
flooded, and short-term flooded conditions. Within each plot pair, sap flux
densities in palms or trees were monitored simultaneously with thermal
dissipation probes. In plot pairs with non-flooded valleys, sap flux densities of
oil palms were only slightly different between the topographic positions, whereas
sap flux densities of rubber trees were higher in the valley than at the
according upland site. In pairs with long-term flooded valleys, sap flux
densities in valleys were lower than at upland plots for both species, but the
reduction was far less pronounced in oil palms than in rubber trees (-22 and -45%
in maximum sap flux density, respectively). At these long-term flooded valley
plots palm and tree water use also responded less sensitively to fluctuations in
micrometeorological variables than at upland plots. In short-term flooded valley
plots, sap flux densities of oil palm were hardly affected by flooding, but sap
flux densities of rubber trees were reduced considerably. Topographic position
and flooding thus affected water use patterns in both oil palms and rubber trees,
but the changes in rubber trees were much more pronounced: compared to non
flooded upland sites, the different flooding conditions at valley sites amplified
the observed heterogeneity of plot mean water use by a factor of 2.4 in oil palm
and by a factor of 4.2 in rubber plantations. Such strong differences between
species as well as the pronounced heterogeneity of water use across space and
time may be of relevance for eco-hydrological assessments of tropical plantation
landscapes.
PMID- 28421092
TI - Manipulation of ABA Content in Arabidopsis thaliana Modifies Sensitivity and
Oxidative Stress Response to Dickeya dadantii and Influences Peroxidase Activity.
AB - The production of reactive oxygen species (ROS) is one of the first defense
reactions induced in Arabidopsis in response to infection by the pectinolytic
enterobacterium Dickeya dadantii. Previous results also suggest that abscisic
acid (ABA) favors D. dadantii multiplication and spread into its hosts. Here, we
confirm this hypothesis using ABA-deficient and ABA-overproducer Arabidopsis
plants. We investigated the relationships between ABA status and ROS production
in Arabidopsis after D. dadantii infection and showed that ABA status modulates
the capacity of the plant to produce ROS in response to infection by decreasing
the production of class III peroxidases. This mechanism takes place independently
of the well-described oxidative stress related to the RBOHD NADPH oxidase. In
addition to this weakening of plant defense, ABA content in the plant correlates
positively with the production of some bacterial virulence factors during the
first stages of infection. Both processes should enhance disease progression in
presence of high ABA content. Given that infection increases transcript abundance
for the ABA biosynthesis genes AAO3 and ABA3 and triggers ABA accumulation in
leaves, we propose that D. dadantii manipulates ABA homeostasis as part of its
virulence strategy.
PMID- 28421093
TI - Enhanced Growth Performance and Salinity Tolerance in Transgenic Switchgrass via
Overexpressing Vacuolar Na+ (K+)/H+ Antiporter Gene (PvNHX1).
AB - Switchgrass (Panicum virgatum L.) has been increasingly recognized as one of the
most valuable perennial bioenergy crop. To improve its biomass production,
especially under salt stress, we isolated a putative vacuolar Na+ (K+)/H+
antiporter gene from switchgrass and designated as PvNHX1. Subcellular
localization revealed that this protein was localized mainly on the vacuole
membrane. The PvNHX1 was found to be expressed throughout the entire growth
period of switchgrass, exhibited preferentially expressed in the leaf tissue, and
highly induced by salt stress. Transgenic switchgrass overexpressing PvNHX1
showed obvious advantages with respect to plant height and leaf development
compared to the wild-type (WT) and transgenic control (EV, expressing the empty
vector only) plants, suggesting PvNHX1 may serve as a promoter in switchgrass
growth and development. Moreover, transgenic switchgrass were more tolerant than
control plants with better growth-related phenotypes (higher shoot height, larger
stem diameter, longer leaf length, and width) and physiological capacities
(increased proline accumulation, reduced malondialdehyde production, preserved
cell membrane integrity, etc.) under high salinity stress. Furthermore, the genes
related to cell growth, flowering, and potassium transporters in transgenic
switchgrass exhibited a different expression profiles when compared to the
control plants, indicating a pivotal function of PvNHX1 in cell expansion and K+
homeostasis. Taken together, PvNHX1 is essential for normal plant growth and
development, and play an important role in the response to salt stress by
improving K+ accumulation. Our data provide a valuable foundation for further
researches on the molecular mechanism and physiological roles of NHXs in plants.
PMID- 28421094
TI - Cucumber CsBPCs Regulate the Expression of CsABI3 during Seed Germination.
AB - Cucumber seeds with shallow dormancy start to germinate in fruit that are
harvested late. ABSCISIC ACID INSENSITIVE3 (ABI3), a transcription factor in the
abscisic acid (ABA) signaling pathway, is one of the most important regulators in
the transition from late embryogenesis to germination. Our analysis found a
candidate cis-regulatory motif for cucumber BASIC PENTACYSTEINE (CsBPC) in the
promoter of CsABI3. Yeast one-hybrid and chromatin immunoprecipitation (ChIP)
assays showed that CsBPCs bound to the promoter of CsABI3. Examination of beta
glucuronidase (GUS) activity driven by the CsABI3 promoter in transgenic
Arabidopsis thaliana plants overexpressing CsBPCs and a Nicotiana benthamiana
(tobacco) luciferase assay indicated that CsBPCs inhibited the expression of
CsABI3. Transgenic plants overexpressing CsBPCs were constructed to confirm that
CsBPCs participates in the control of seed germination. This study of the
cucumber BPC-ABI3 pathway will help to explore and characterize the molecular
mechanisms underlying seed germination and will provide necessary information for
seed conservation in agriculture and forestry.
PMID- 28421095
TI - Exploiting Wild Relatives for Genomics-assisted Breeding of Perennial Crops.
AB - Perennial crops are vital contributors to global food production and nutrition.
However, the breeding of new perennial crops is an expensive and time-consuming
process due to the large size and lengthy juvenile phase of many species.
Genomics provides a valuable tool for improving the efficiency of breeding by
allowing progeny possessing a trait of interest to be selected at the seed or
seedling stage through marker-assisted selection (MAS). The benefits of MAS to a
breeder are greatest when the targeted species takes a long time to reach
maturity and is expensive to grow and maintain. Thus, MAS holds particular
promise in perennials since they are often costly and time-consuming to grow to
maturity and evaluate. Well-characterized germplasm that breeders can tap into
for improving perennials is often limited in genetic diversity. Wild relatives
are a largely untapped source of desirable traits including disease resistance,
fruit quality, and rootstock characteristics. This review focuses on the use of
genomics-assisted breeding in perennials, especially as it relates to the
introgression of useful traits from wild relatives. The identification of genetic
markers predictive of beneficial phenotypes derived from wild relatives is
hampered by genomic tools designed for domesticated species that are often ill
suited for use in wild relatives. There is therefore an urgent need for better
genomic resources from wild relatives. A further barrier to exploiting wild
diversity through genomics is the phenotyping bottleneck: well-powered genetic
mapping requires accurate and cost-effective characterization of large
collections of diverse wild germplasm. While genomics will always be used in
combination with traditional breeding methods, it is a powerful tool for
accelerating the speed and reducing the costs of breeding while harvesting the
potential of wild relatives for improving perennial crops.
PMID- 28421096
TI - Regulation of Banana Phytoene Synthase (MaPSY) Expression, Characterization and
Their Modulation under Various Abiotic Stress Conditions.
AB - Phytoene synthase (PSY) is a key regulatory enzyme of carotenoid biosynthesis
pathway in plants. The present study examines the role of PSY in carotenogenesis
and stress management in banana. Germplasm screening of 10 Indian cultivars
showed that Nendran (3011.94 MUg/100 g dry weight) and Rasthali (105.35 MUg/100 g
dry weight) contained the highest and lowest amounts of beta-carotene,
respectively in ripe fruit-pulp. Nendran ripe pulp also showed significantly
higher antioxidant activity as compared to Rasthali. Meta-analysis of three
banana PSY genes (MaPSY1, MaPSY2, and MaPSY3) was performed to identify their
structural features, subcellular, and chromosomal localization in banana genome.
The distinct expression patterns of MaPSY1, MaPSY2, and MaPSY3 genes were
observed in various tissues, and fruit developmental stages of these two
contrasting cultivars, suggesting differential regulation of the banana PSY
genes. A positive correlation was observed between the expression of MaPSY1 and
beta-carotene accumulation in the ripe fruit-peel and pulp of Nendran. The
presence of stress responsive cis-regulatory motifs in promoter region of MaPSY
genes were correlated with the expression pattern during various stress (abscisic
acid, methyl jasmonate, salicylic acid and dark) treatments. The positive
modulation of MaPSY1 noticed under abiotic stresses suggested its role in plant
physiological functions and defense response. The amino acid sequence analysis of
the PSY proteins in contrasting cultivars revealed that all PSY comprises
conserved domains related to enzyme activity. Bacterial complementation assay has
validated the functional activity of six PSY proteins and among them PSY1 of
Nendran (Nen-PSY1) gave the highest activity. These data provide new insights
into the regulation of PSY expression in banana by developmental and stress
related signals that can be explored in the banana improvement programs.
PMID- 28421097
TI - Development of Incompletely Fused Carpels in Maize Ovary Revealed by miRNA,
Target Gene and Phytohormone Analysis.
AB - Although the molecular basis of carpel fusion in maize ovary development remains
largely unknown, increasing evidence suggests a critical role of microRNAs
(miRNAs). In this study, a combination of miRNA sequencing, degradome and
physiological analyses was used to characterize carpel fusion development in
maize ovaries showing incompletely (IFC) and completely fused carpels (CFC). A
total of 162 known miRNAs distributed across 33 families were identified, of
which 20 were differentially expressed. In addition, 53 miRNA candidates were
identified, of which 10 were differentially expressed in the IFC and CFC ovaries.
In degradome analysis, a total of 113 and 11 target genes were predicted for the
known and novel miRNAs, respectively. Moreover, 24 (60%) target genes of the
differentially expressed known miRNAs were found to code transcription factors,
including auxin response factor (ARF), TB1-CYC-PCFs (TCP), APETALA2 (AP2), growth
regulating factor (GRF), MYB, NAC, and NF-YA, all of which have been shown to
play a role in carpel fusion development. Correlation analysis of these
differentially expressed known miRNAs and their targets with phytohormone signals
revealed significant correlations with at least one phytohormone signal, the main
regulator of carpel fusion development. These results suggest that incomplete
carpel fusion is partly the result of differential expression of certain miRNAs
and their targets. Overall, these findings improve our knowledge of the effect of
miRNA regulation on target expression, providing a useful resource for further
analysis of the interactions between miRNAs, target genes and phytohormones
during carpel fusion development in maize.
PMID- 28421098
TI - Fine-Mapping the Branching Habit Trait in Cultivated Peanut by Combining Bulked
Segregant Analysis and High-Throughput Sequencing.
AB - The growth habit of lateral shoots (also termed "branching habit") is an
important descriptive and agronomic character of peanut. Yet, both the
inheritance of branching habit and the genetic mechanism that controls it in this
crop remain unclear. In addition, the low degree of polymorphism among cultivated
peanut varieties hinders fine-mapping of this and other traits in non-homozygous
genetic structures. Here, we combined high-throughput sequencing with a well
defined genetic system to study these issues in peanut. Initially, segregating F2
populations derived from a reciprocal cross between very closely related Virginia
type peanut cultivars with spreading and bunch growth habits were examined. The
spreading/bunch trait was shown to be controlled by a single gene with no
cytoplasmic effect. That gene was named Bunch1 and was significantly correlated
with pod yield per plant, time to maturation and the ratio of "dead-end" pods.
Subsequently, bulked segregant analysis was performed on 52 completely bunch, and
47 completely spreading F3 families. In order to facilitate the process of SNP
detection and candidate-gene analysis, the transcriptome was used instead of
genomic DNA. Young leaves were sampled and bulked. Reads from Illumina sequencing
were aligned against the peanut reference transcriptome and the diploid genomes.
Inter-varietal SNPs were detected, scored and quality-filtered. Thirty-four
candidate SNPs were found to have a bulk frequency ratio value >10 and 6 of those
SNPs were found to be located in the genomic region of linkage group B5. Three
best hits from that over-represented region were further analyzed in the
segregating population. The trait locus was found to be located in a ~1.1 Mbp
segment between markers M875 (B5:145,553,897; 1.9 cM) and M255 (B5:146,649,943;
2.25 cM). The method was validated using a population of recombinant inbreed
lines of the same cross and a new DNA SNP-array. This study demonstrates the
relatively straight-forward utilization of bulk segregant analysis for trait fine
mapping in the low polymeric and heterozygous germplasm of cultivated peanut and
provides a baseline for candidate gene discovery and map-based cloning of Bunch1.
PMID- 28421099
TI - Progress in High-Amylose Cereal Crops through Inactivation of Starch Branching
Enzymes.
AB - High-amylose cereal starches provide many health benefits for humans. The
inhibition or mutation of starch branching enzyme (SBE) genes is an effective
method to develop high-amylose cereal crops. This review summarizes the
development of high-amylose cereal crops through the inactivation of one or more
SBE isoforms or combination with other genes. This review also reveals the causes
of increase in amylose content in high-amylose crops. A series of changes,
including amylopectin structure, crystalline structure, thermal properties, and
hydrolysis properties, occurs as amylose content increases. The different
morphological starch granules nominated as heterogeneous starch granules or
differently stained starch granules are detected in high-amylose cereal crops.
Detailed studies on four heterogeneous starch granules in high-amylose rice,
which is developed by antisense RNA inhibition of SBEI/IIb, indicate that
granules with different morphologies possess various molecular structures and
physicochemical and functional properties. This variation diversifies their
applications in food and non-food industries. However, current knowledge
regarding how these heterogeneous starch granules form and why they exhibit
regional distribution in endosperm remain largely unknown.
PMID- 28421100
TI - Integrated Approach of Agri-nanotechnology: Challenges and Future Trends.
AB - Nanotechnology representing a new frontier in modern agriculture is anticipated
to become a major thrust in near future by offering potential applications. This
integrating approach, i.e., agri-nanotechnology has great potential to cope with
global challenges of food production/security, sustainability and climate change.
However, despite the potential benefits of nanotechnology in agriculture so far,
their relevance has not reached up to the field conditions. The elevating
concerns about fate, transport, bioavailability, nanoparticles toxicity and
inappropriateness of regulatory framework limit the complete acceptance and
inclination to adopt nanotechnologies in agricultural sector. Moreover, the
current research trends lack realistic approach that fail to attain comprehensive
knowledge of risk assessment factors and further toxicity of nanoparticles toward
agroecosystem components viz. plant, soil, soil microbiomes after their release
into the environment. Hence in the present review we attempt to suggest certain
key points to be addressed in the current and future agri-nanotechnology
researches on the basis of recognized knowledge gaps with strong recommendation
of incorporating biosynthesized nanoparticles to carry out analogous functions.
In this perspective, the major points are as follows: (i) Mitigating risk
assessment factors (responsible for fate, transport, behavior, bioavailability
and toxicity) for alleviating the subsequent toxicity of nanoparticles. (ii)
Optimizing permissible level of nanoparticles dose within the safety limits by
performing dose dependent studies. (iii) Adopting realistic approach by designing
the experiments in natural habitat and avoiding in vitro assays for accurate
interpretation. (iv) Most importantly, translating environmental friendly and non
toxic biosynthesized nanoparticles from laboratory to field conditions for
agricultural benefits.
PMID- 28421101
TI - Hyperspectral Technologies for Assessing Seed Germination and Trifloxysulfuron
methyl Response in Amaranthus palmeri (Palmer Amaranth).
AB - Weed infestations in agricultural systems constitute a serious challenge to
agricultural sustainability and food security worldwide. Amaranthus palmeri S.
Watson (Palmer amaranth) is one of the most noxious weeds causing significant
yield reductions in various crops. The ability to estimate seed viability and
herbicide susceptibility is a key factor in the development of a long-term
management strategy, particularly since the misuse of herbicides is driving the
evolution of herbicide response in various weed species. The limitations of most
herbicide response studies are that they are conducted retrospectively and that
they use in vitro destructive methods. Development of a non-destructive method
for the prediction of herbicide response could vastly improve the efficacy of
herbicide applications and potentially delay the evolution of herbicide
resistance. Here, we propose a toolbox based on hyperspectral technologies and
data analyses aimed to predict A. palmeri seed germination and response to the
herbicide trifloxysulfuron-methyl. Complementary measurement of leaf
physiological parameters, namely, photosynthetic rate, stomatal conductence and
photosystem II efficiency, was performed to support the spectral analysis. Plant
response to the herbicide was compared to image analysis estimates using mean
gray value and area fraction variables. Hyperspectral reflectance profiles were
used to determine seed germination and to classify herbicide response through
examination of plant leaves. Using hyperspectral data, we have successfully
distinguished between germinating and non-germinating seeds, hyperspectral
classification of seeds showed accuracy of 81.9 and 76.4%, respectively.
Sensitive and resistant plants were identified with high degrees of accuracy
(88.5 and 90.9%, respectively) from leaf hyperspectral reflectance profiles
acquired prior to herbicide application. A correlation between leaf physiological
parameters and herbicide response (sensitivity/resistance) was also demonstrated.
We demonstrated that hyperspectral reflectance analyses can provide reliable
information about seed germination and levels of susceptibility in A. palmeri.
The use of reflectance-based analyses can help to better understand the
invasiveness of A. palmeri, and thus facilitate the development of targeted
control methods. It also has enormous potential for impacting environmental
management in that it can be used to prevent ineffective herbicide applications.
It also has potential for use in mapping tempo-spatial population dynamics in
agro-ecological landscapes.
PMID- 28421103
TI - SVP-like MADS Box Genes Control Dormancy and Budbreak in Apple.
AB - The annual growth cycle of trees is the result of seasonal cues. The onset of
winter triggers an endodormant state preventing bud growth and, once a chilling
requirement is satisfied, these buds enter an ecodormant state and resume
growing. MADS-box genes with similarity to Arabidopsis SHORT VEGETATIVE PHASE
(SVP) [the SVP-like and DORMANCY ASSOCIATED MADS-BOX (DAM) genes] have been
implicated in regulating flowering and growth-dormancy cycles in perennials.
Here, we identified and characterized three DAM-like (MdDAMs) and two SHORT
VEGETATIVE PHASE-like (MdSVPs) genes from apple (Malus * domestica 'Royal Gala').
The expression of MdDAMa and MdDAMc indicated they may play a role in triggering
autumn growth cessation. In contrast, the expression of MdDAMb, MdSVPa and MdSVPb
suggested a role in maintaining bud dormancy. Consistent with this, ectopic
expression of MdDAMb and MdSVPa in 'Royal Gala' apple plants resulted in delayed
budbreak and architecture change due to constrained lateral shoot outgrowth, but
normal flower and fruit development. The association of MdSVPa and MdSVPb
expression with floral bud development in the low fruiting 'Off' trees of a
biennial bearing cultivar 'Sciros' suggested the SVP genes might also play a role
in floral meristem identity.
PMID- 28421102
TI - Ethylene Role in Plant Growth, Development and Senescence: Interaction with Other
Phytohormones.
AB - The complex juvenile/maturity transition during a plant's life cycle includes
growth, reproduction, and senescence of its fundamental organs: leaves, flowers,
and fruits. Growth and senescence of leaves, flowers, and fruits involve several
genetic networks where the phytohormone ethylene plays a key role, together with
other hormones, integrating different signals and allowing the onset of
conditions favorable for stage progression, reproductive success and organ
longevity. Changes in ethylene level, its perception, and the hormonal crosstalk
directly or indirectly regulate the lifespan of plants. The present review
focused on ethylene's role in the development and senescence processes in leaves,
flowers and fruits, paying special attention to the complex networks of ethylene
crosstalk with other hormones. Moreover, aspects with limited information have
been highlighted for future research, extending our understanding on the
importance of ethylene during growth and senescence and boosting future research
with the aim to improve the qualitative and quantitative traits of crops.
PMID- 28421104
TI - Evolving Tale of TCPs: New Paradigms and Old Lacunae.
AB - Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key
mediators of genetic innovations underlying morphological novelties, stress
adaptation, and evolution of immune response in plants. They have a remarkable
ability to integrate and translate diverse endogenous, and environmental signals
with high fidelity. Compilation of studies, aimed at elucidating the mechanism of
TCP functions, shows that it takes an amalgamation and interplay of several
different factors, regulatory processes and pathways, instead of individual
components, to achieve the incredible functional diversity and specificity,
demonstrated by TCP proteins. Through this minireview, we provide a brief
description of key structural features and molecular components, known so far,
that operate this conglomerate, and highlight the important conceptual challenges
and lacunae in TCP research.
PMID- 28421105
TI - Nitrate: A Crucial Signal during Lateral Roots Development.
AB - Root plasticity is an important trait for plants to forage nutrient and adapt to
survival in a complicated environment. Lateral roots (LRs) are generally more
sensitive than primary roots in response to changing environmental conditions. As
the main source of nitrogen for most higher plants, nitrate acting as a signal
has received great attention in the regulation of LR development. In general,
there are dual effects including stimulatory and inhibitory of low nitrate on LR
development; while high nitrate supply has an inhibitory effect on LR
development; nitrate heterogeneity also has a stimulatory effect on LR
development in [Formula: see text]- rich zone. Here, we focus on recent
progresses in the role of a nitrate signal in the regulation of the LRs
development.
PMID- 28421106
TI - The Synergistic Responses of Different Photoprotective Pathways in Dwarf Bamboo
(Fargesia rufa) to Drought and Subsequent Rewatering.
AB - : Dwarf bamboo-dominated forests are often subjected to temporary periods of
drought due to rising air temperature and decreasing rainfall. Nevertheless, the
relationship among CO2 assimilation, photoprotective pathways and metabolism of
reactive oxygen species (ROS) remains unexplored in bamboo species. Changes in
leaf gas exchange, chlorophyll fluorescence, energy partitioning, antioxidative
system and compounds related to ROS metabolism in Fargesia rufa plants subjected
to drought and subsequent rewatering were analyzed. Drought resulted in a
reversible inhibition of photochemistry, particularly net CO2 assimilation, and
lipid peroxidation due to ROS accumulation. Meanwhile, photoprotective pathways,
including the water-water cycle (especially for moderate drought), and adjustment
in antenna pigments, thermal dissipation and antioxidative defense capacity at
organelle levels (especially for severe drought), were up-regulated at the stress
phase. Conversely, photorespiration was down-regulated after drought stress. As a
result, rewatering restored most of the photochemical activity under drought,
especially moderate drought. Moreover, thermal dissipation under severe drought
was still operated for avoiding high ROS levels after rewatering. Therefore, the
synergistic function of these photoprotective pathways except photorespiration
can protect the photosynthetic apparatus from oxidative damage in response to
varying intensities of drought stress when CO2 assimilation is restricted. This
is helpful for the gradual recovery of photosynthetic capacity after rewatering.
Thus, F. rufa plants can withstand drought and is capable of survival in such
environment. HIGHLIGHTS: 1. The effects of drought and subsequent rewatering on
Fargesia rufa were studied.2. Drought resulted in a reversible inhibition of
photochemistry.3. Photoprotective pathways except photorespiration were up
regulated at the drought phase.4. Rewatering rapidly restored photochemical
activity, especially under moderate drought.5. Fargesia rufa plant is capable of
resisting and surviving drought environment.
PMID- 28421107
TI - Sexual Dimorphism of miRNAs Secreted by Bovine In vitro-produced Embryos.
AB - Sexual dimorphism of bovine blastocysts has previously been observed through
differences in development, cell death, metabolism, telomere length, DNA
methylation, and transcriptomics. However, dimorphism in the secretion of miRNAs
to culture media has not yet been evaluated. The objectives of this study were to
determine if sex-specific blastocyst miRNA secretion occurs and to further
investigate the role these miRNAs may have in the interaction between a
blastocyst and the maternal environment. In vitro embryo culture was performed
and media from male and female blastocysts was collected into sex-specific pools.
Profiling of 68 miRNAs revealed a total of eight miRNAs that were differentially
expressed between female and male-conditioned media. Validation by qPCR confirmed
higher expression of miR-22 (P < 0.05), miR-122 (P < 0.05), and miR-320a (P <
0.05) in female media for three additional biological replicates. To examine the
potential roles of secreted miRNAs to the media in communication with the
maternal environment, miR-22, miR-122, and miR-320a were each supplemented to
four replicates of primary bovine endometrial epithelial cell culture. Uptake of
miR-122 (P < 0.05) and miR-320a (P < 0.05) was detected, and a trend of uptake
was detected for miR-22 (P > 0.05). Further, expression of the progesterone
receptor transcript, a predicted target of all three miRNAs, was found to be
upregulated in the cells following supplementation of miR-122 (P < 0.05) and miR
320a (P < 0.05), and a trend upregulation of the transcript was observed
following miR-22 (P > 0.05) supplementation. This work demonstrates that male and
female conceptuses are able to differentially secrete miRNAs at the blastocyst
stage and that these miRNAs have the ability to induce a transcriptomic response
when applied to maternal cells. This knowledge builds on the known dimorphic
differences in conceptuses at the blastocyst stage and demonstrates a role for
blastocyst-secreted miRNAs in cell-cell communication.
PMID- 28421108
TI - The Effect of Hepatosteatosis on Response to Antiviral Treatment in Patients with
Chronic Hepatitis B: A Meta-Analysis.
AB - Background. This study is to systematically analyze the effects of
hepatosteatosis on the response to antiviral treatment in patients with chronic
hepatitis B (CHB) and hepatosteatosis. Methods. Systematic search was performed
in PubMed, Embase, Web of Science, Elsevier, and the Chinese BioMedical
literature databases for relevant studies published until February 2016.
Treatment outcomes were compared between patients with CHB plus concomitant
hepatosteatosis and those without hepatosteatosis. Results. A total of 8
prospective cohort studies (399 patients with CHB plus hepatosteatosis and 688
patients with only CHB) were included. Biochemical and virological response at
both 48 and 96 weeks were significantly lower in patients with CHB plus
hepatosteatosis as compared to that in patients with only CHB. Subgroup analysis
based on methods used for diagnosis of hepatosteatosis and treatment regimens
showed that when hepatosteatosis was diagnosed on Doppler ultrasound and treated
with nucleotide analogues, patients with CHB plus hepatosteatosis showed lower
biochemical (62.7% versus 75.8%, P = 0.002) and virological response (66.2%
versus 72.3%, P = 0.006) as compared to that in patients with CHB. Conclusion.
Hepatosteatosis lowers the efficacy of antiviral treatment in patients with CHB,
especially when hepatosteatosis was diagnosed on ultrasound findings and treated
with nucleotide analogues.
PMID- 28421109
TI - Bleeding Meckel's Diverticulum in Children: The Diagnostic Value of Double
Balloon Enteroscopy.
AB - Background. Meckel's diverticulum (MD) is the most common congenital anomaly of
the gastrointestinal tract. The purpose of this study was to evaluate the
diagnostic value and safety of double-balloon enteroscopy (DBE) for bleeding MD
in children. Methods. We included consecutive children who were highly suspected
of MD between 2012 and 2013. All patients underwent Meckel's scan. DBE was
performed for patient with negative Meckel's scan. An exploratory laparoscopy was
performed in children with positive Meckel's scan or DBE. Results. 42 patients
met the inclusion criteria. 40 patients were confirmed to have MD by exploratory
laparoscopy. Meckel's scan was positive in 36 and negative in 6, with 34 as true
positives and 2 as false positives. Six patients with negative Meckel's scan were
found to have MD by retrograde DBE and had immediate operation. The distance from
the diverticulum to the ileocecal valve was 40 to 60 cm. Ectopic gastric mucosa
was present in all 6 patients (100%). After operation, patients were followed in
clinic for 20 to 42 months and no evidence of GI bleeding or recurrent anemia was
observed. Conclusions. Double-balloon enteroscopy can be a reliable diagnostic
tool for bleeding Meckel's diverticulum in children with negative Meckel's scan.
PMID- 28421110
TI - Prognostic Evaluation of Vimentin Expression in Correlation with Ki67 and CD44 in
Surgically Resected Pancreatic Ductal Adenocarcinoma.
AB - Purpose. Radical surgical resection with adjuvant chemotherapy or chemo
radiotherapy is the most effective treatment for pancreatic ductal adenocarcinoma
(PDAC). However, relatively few studies investigate the prognostic significance
of biological markers in PDAC. This study aims to look into the expressions of
vimentin, Ki67, and CD44 in PDAC surgical specimens and their potential
prognostic implications in survival. Method. The study was designed as
retrospective, and vimentin, Ki67, and CD44 expressions were evaluated by
immunohistochemistry in 53 pancreatic ductal adenocarcinoma cases. Overall
survival was assessed by the Kaplan-Meier method. Results. Patients' median age
was 68 years. The median survival was 18 months. The tumors were T3-4 in 40/53
(75.5%), and metastases in lymph nodes were found in 42 out of 53 (79.2%) cases.
On multivariate analysis, the size of primary tumor (p < 0.001), the surgical
resection margin status (p = 0.042), and vimentin expression (p = 0.011) were
independently correlated with overall survival. Conclusions. Long-term survival
after resection of PDAC is still about 15%. Vimentin expression is a potential
independent adverse prognostic molecular marker and should be included in
histopathological reports. Also, CD44 expression correlates with high Ki67,
vimentin positivity, and N stage and may represent a potential target of novel
therapeutic modalities in pancreatic adenocarcinoma patients.
PMID- 28421111
TI - XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with
Male Infertility Risk: Evidences from Case-Control and In Silico Studies.
AB - We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6
61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men
including 178 infertile males (102 idiopathic azoospermia and 76 severe
oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7
6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by
PCR. The 2R allele and 2R allele carriers of XRCC5 VNTR polymorphism
significantly decreased risk of male infertility. The mutant GG genotypes and
carriers of the CG and GG genotypes of XRCC6 -61C>G showed increased risk for the
male infertility. Furthermore, the G allele of the XRCC6 -61C>G was correlated
with increased susceptibility to male infertility. Likewise, the T allele of the
XRCC7 6721G>T polymorphism was associated with increased susceptibility to male
infertility in azoospermia. In silico analysis predicted that the presence of
tandem repeats in XRCC5 gene prompter can be sequence to bind to more nuclear
factors. Also, rs2267437 (C>G) variant was located in a well-conserved region in
XRCC6 promoter and this variation might lead to differential allelic expression.
The XRCC7 6721G>T gene polymorphism occurred in an acceptor-splicing site, but
this polymorphism has no severe modification on XRCC7 mRNA splicing. Our results
indicate the association of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T gene
polymorphisms with male infertility in Iranian men.
PMID- 28421112
TI - Self-Monitoring of Blood Glucose to Assess Dawn Phenomenon in Chinese People with
Type 2 Diabetes Mellitus.
AB - Aims. We investigated whether self-monitoring of blood glucose could be used to
assess dawn phenomenon in Chinese people with type 2 diabetes mellitus (T2DM).
Methods. A total of 306 people with T2DM underwent continuous glucose monitoring
and self-monitoring of blood glucose for 72 h. A linear model was used to fit the
optimal linear formula of the magnitude of dawn phenomenon (DeltaDawn) and self
monitoring of blood glucose values. Results. The prevalence of dawn phenomenon
was similar within different oral antidiabetic drug groups (42.5%, 31.5%, and
40.9%, P = 0.216). Multiple variable linear regression showed that prebreakfast,
prelunch, and predinner glucose measurements were independently and significantly
correlated with DeltaDawn. The linear formula between DeltaDawn and blood glucose
was as follows: DeltaDawn (mg/dL) = 0.557 * prebreakfast - 0.065 * prelunch -
0.164 * predinner - 20.894 (mg/dL) (adjusted R2 = 0.302, P = 0.000). Conclusions.
Dawn phenomenon could be partly assessed by blood glucose self-monitoring in
Chinese people with T2DM using the abovementioned formula. The incidence of dawn
phenomenon was similar among patients in different oral antidiabetic drug groups.
PMID- 28421113
TI - Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body
Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in
the Brain.
AB - The brain is vulnerable to hypoglycaemia due to a continuous need of energy
substrates to meet its high metabolic demands. Studies have shown that severe
acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain,
when neuroglycopenia cannot be evaded despite increased levels of cerebral
glucose transporters. Compensatory measures in the brain during chronic insulin
induced hypoglycaemia are less well understood. The present study investigated
how the brain of nondiabetic rats copes with chronic insulin-induced
hypoglycaemia for up to eight weeks. Brain level of different substrate
transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks
consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in
controls). The animals had increased food consumption, body weights, and
hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose
transporter were decreased, whereas levels of lipid peroxidation products were
unchanged. Discontinued infusion was followed by transient systemic
hyperglycaemia and decreased food consumption and body weight. After 4 weeks,
plasma levels of lipid peroxidation products were increased, possibly as a
consequence of hyperglycaemia-induced oxidative stress. The present data suggests
that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body
weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose
transporter levels, which may be leptin-induced.
PMID- 28421115
TI - Radix Entomolaris in the Mandibular Molar Teeth of an Iranian Population.
AB - Purpose. Supernumerary roots in permanent mandibular molar teeth make endodontic
treatment more complicated. The aim of this study was to determine the prevalence
of Radix Entomolaris (RE) in permanent mandibular first and second molars in the
population of Kerman, in the southeast of Iran. Materials and Methods. From a
collection of 500 mandibular first and second molar teeth extracted over 2015
2016 at dental clinics in Kerman, teeth were scored for an additional
distolingual root, and the average root length and root morphology of this extra
root were determined using the De Moor classification scheme. Results. In this
population, RE occurred in 6% of mandibular first molars (4% with a straight apex
(Type I) and 2% with buccal apical curvature (Type III)). In all cases, RE was
the shortest root, with an average root length of 18.37 mm. RE occurred in only
0.8% of mandibular second molars, with an average root length of 18.0 mm. All
mandibular second molars with RE were of Type III. Fisher's exact test showed
that the difference in frequency between first and second molars was
statistically significant (two-sided P = 0.002). Conclusion. Radix Entomolaris
occurs more frequently in mandibular first molars than in mandibular second
molars in this sample of 500 mandibular molars. The reported rate of 6% in first
molars is expected to be higher than reported rates in European or Caucasian
populations where the prevalence is typically less than 2%.
PMID- 28421116
TI - Mitochondrial Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes.
AB - Human pluripotent stem cells derived cardiomyocytes (PSC-CMs) have been widely
used for disease modeling, drug safety screening, and preclinical cell therapy to
regenerate myocardium. Most studies have utilized PSC-CM grown in vitro for a
relatively short period after differentiation. These PSC-CMs demonstrated
structural, electrophysiological, and mechanical features of primitive
cardiomyocytes. A few studies have extended in vitro PSC-CM culture time and
reported improved maturation of structural and electromechanical properties. The
degree of mitochondrial maturation, however, remains unclear. This study
characterized the development of mitochondria during prolonged in vitro culture.
PSC-CM demonstrated an improved mitochondrial maturation with prolonged culture,
in terms of increased mitochondrial relative abundance, enhanced membrane
potential, and increased activity of several mitochondrial respiratory complexes.
These are in parallel with the maturation of other cellular components. However,
the maturation of mitochondria in PSC-CMs grown for extended in vitro culture
exhibits suboptimal maturation when compared with the maturation of mitochondria
observed in the human fetal heart during similar time interval.
PMID- 28421114
TI - Status of Epstein-Barr Virus Coinfection with Helicobacter pylori in Gastric
Cancer.
AB - Epstein-Barr virus is a ubiquitous human herpesvirus whose primary infection
causes mononucleosis, Burkett's lymphoma, nasopharyngeal carcinoma, autoimmune
diseases, and gastric cancer (GC). The persistent infection causes malignancies
in lymph and epithelial cells. Helicobacter pylori causes gastritis in human with
chronic inflammation. This chronic inflammation is thought to be the cause of
genomic instability. About 45%-word population have a probability of having both
pathogens, namely, H. pylori and EBV. Approximately 180 per hundred thousand
population is developing GC along with many gastric abnormalities. This makes GC
the third leading cause of cancer-related death worldwide. Although lots of
research are carried out individually for EBV and H. pylori, still there are very
few reports available on coinfection of both pathogens. Recent studies suggested
that EBV and H. pylori coinfection increases the occurrence of GC as well as the
early age of GC detection comparing to individual infection. The aim of this
review is to present status on coinfection of both pathogens and their
association with GC.
PMID- 28421117
TI - Chronic Pain in Children: A Look at the Referral Process to a Pediatric Pain
Clinic.
AB - We reviewed the referral pattern of children with chronic pain to a specialized
pediatric pain clinic. Data were obtained from referring physicians and medical
records and during an interview with patients and their parents by physicians and
a psychologist. We analyzed the following: referral diagnosis, demographics,
duration of symptoms, number of physicians previously consulted, school
attendance, sports activities, presence of psychological disorders, final team
diagnosis, and outcomes. Children had been experiencing pain for 34 +/- 55
months. Patients had consulted on average 3 physicians in addition to their
pediatrician. 32% of the patients had missed at least 10 days of school in a
calendar year, and 47% had stopped playing sports. 15% had an operation because
of pain that had been unsuccessful. The most common missed diagnosis was anxiety
(25%) and depression (13%). 69% of the patients were back to school and/or
playing sports within 4 months from our initial consultation. 32% of the patients
did not make any progress during the follow-up period. The most common reasons
for failure to improve were no compliance with the recommended treatments and
poorly controlled major mood disorder. The time to refer children with chronic
pain for specialized care could be extremely long causing significant social and
psychological consequence.
PMID- 28421118
TI - Pattern of Traditional Medicine Utilization among HIV/AIDS Patients on
Antiretroviral Therapy at a University Hospital in Northwestern Ethiopia: A Cross
Sectional Study.
AB - The objective of this study was to assess traditional, complementary, and
alternative medicine (TCAM) utilization pattern among HIV/AIDS patients on
antiretroviral therapy at University of Gondar Comprehensive Specialized
Hospital. Materials and Methods. Data on sociodemographic profile and clinical
and TCAM utilization were collected using a structured, pretested questionnaire
from April 01 to May 28, 2014, through interviews with patients. Data on CD4
count, HIV stage, and ART regimen were collected from patient records. Analysis
was conducted descriptively using SPSS version 20. Results. Of the 300
participants, 43.7% reported using TCAM, with the largest proportion of them from
religious institutions (churches/mosques) (41.22%), followed by home prepared
(32.82%) and traditional healers (16.03%). The leading forms of TCAM used were
spiritual and herbal therapies constituting 56.49% and 36.64% of the patients,
respectively. The most frequently used herbal products included Nigella sativa
(22.92%) and Moringa oleifera (20.83%). Most of the patients (73.30%) using TCAM
reported improvement in their conditions. Conclusions. TCAM utilization among
HIV/AIDS patients on ART was common and different sources and types were used
alongside ART, with improvement reported by most. Further research is needed to
identify CAM therapies which may be used as adjunct treatments among these
patients.
PMID- 28421119
TI - Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula,
on the Main CYP450 Activities in Rats Using a Cocktail Method.
AB - The purpose of this work was to study the influences of Realgar-Indigo naturalis
(RIF) and its principal element realgar on 4 main cytochrome P450 enzymes
activities in rats. A simple and efficient cocktail method was developed to
detect the four probe drugs simultaneously. In this study, Wistar rats were
administered intragastric RIF and realgar for 14 days; mixed probe drugs were
injected into rats by caudal vein. Through analyzing the pharmacokinetic
parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The
results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11
enzyme activity significantly. Interestingly, in realgar high dosage group,
CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of
realgar manifested a good dose-dependent manner. The RIF results indicated that
drug coadministrated with RIF may need to be paid attention in relation to drug
drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM),
does have curative effect on acute promyelocytic leukemia (APL). Its toxicity
studies should be focused on. We found that, in realgar high dosage group,
CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its
potential toxicity mechanism.
PMID- 28421120
TI - In Vitro and In Vivo Studies on Quercus acuta Thunb. (Fagaceae) Extract: Active
Constituents, Serum Uric Acid Suppression, and Xanthine Oxidase Inhibitory
Activity.
AB - Quercus acuta Thunb. (Fagaceae) (QA) is cultivated as a dietary and ornamental
plant in China, Japan, South Korea, and Taiwan. It has been widely used as the
main ingredient of acorn tofu, a traditional food in China and South Korea. The
aim of this study was to determine in vitro and in vivo xanthine oxidase (XO)
inhibitory and antihyperuricemic activities of an ethyl acetate extract of QA
leaf (QALE) and identify its active phytochemicals using gas chromatography-mass
spectrometry (GC-MS) and liquid chromatography (LC) systems. The QALE was found
to possess potent in vitro antioxidant and XO inhibitory activities. In vivo
study using hyperuricemic mice induced with potassium oxonate demonstrated that
the QALE could inhibit hepatic XO activity at a relatively low oral dose (50
mg/kg) and significantly alleviate hyperuricemia to a similar extent as
allopurinol. Several active compounds including vitamin E known to possess XO
inhibitory activity were identified from the QALE. To the best of our knowledge,
this is the first study that reports the active constituents and
antihyperuricemic effect of QA, suggesting that it is feasible to use QALE as a
food therapy or alternative medicine for alleviating hyperuricemia and gout.
PMID- 28421121
TI - Availability, Pharmaceutics, Security, Pharmacokinetics, and Pharmacological
Activities of Patchouli Alcohol.
AB - Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical
bioactive ingredients and is mainly isolated from aerial part of Pogostemon
cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has
been widely applied in perfume industries. This review was written with the use
of reliable information published between 1974 and 2016 from libraries and
electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect,
Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of
security, pharmacokinetics, and bioactivities of PA and at further providing a
potential guide in exploring the PA and its use in various medical fields. We
found that PA maybe was a low toxic drug that was acquired numerously through
vegetable oil isolation and chemical synthesis and its stability and low water
dissolution were improved in pharmaceutics. It also possessed specific
pharmacokinetic characteristics, such as two-compartment open model, first-order
kinetic elimination, and certain biometabolism and biotransformation process, and
was shown to have multiple biological activities, that is, immunomodulatory, anti
inflammatory, antioxidative, antitumor, antimicrobial, insecticidal,
antiatherogenic, antiemetic, whitening, and sedative activity. However, the
systematic evaluations of preparation, pharmaceutics, toxicology,
pharmacokinetics, and bioactivities underlying molecular mechanisms of action
also required further investigation prior to practices of PA in clinic.
PMID- 28421123
TI - Study of the Hypoglycemic Activity of Derivatives of Isoflavones from Cicer
arietinum L.
AB - The chickpea, a food and medicine used by the people of Xinjiang, has a
beneficial hypoglycemic effect. To better utilize this national resource and
develop hypoglycemic agents from components of the chickpea, a series of new
derivatives of isoflavone compounds from the chickpea were synthesized. An
insulin-resistant (IR) HepG2 cell model was used to screen the hypoglycemic
activities of these compounds. And the structure-activity relationships of these
compounds were explored. Additionally, several combinations of these compound
displayed higher hypoglycemic activity than any single compound, and they had
similar hypoglycemic activity to that of the positive control group (p > 0.05).
In addition, combination 3 and combination 6 exerted different effects on the
insulin sensitivity of H4IIE cells stimulated with resistin. And the results
indicated that combination 3 would have higher hypoglycemic activity. These
findings demonstrate the characteristics of multiple components and targets of
Chinese herbal medicine. This evidence may provide new ideas for the development
of hypoglycemic drugs.
PMID- 28421122
TI - Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri
Root Extract against Hepatocellular Carcinoma Cells.
AB - Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This
study was performed to investigate the antiproliferative effects of moghat root
extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC)
cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked
immunosorbent assay, caspase and apoptotic activation, flow cytometry, and
immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 +/- 6 MUg/ml)
and for Hep3B (1510 +/- 5 MUg/ml) induced significant growth-inhibitory effects
against HCC cells, with no cytotoxic effect on normal hepatocytes. MRE treatment
induced apoptotic effects to HepG2 cells in a caspase-dependent manner and via
upregulating p53/p21 and PCNA. The upregulation of p21 was controlled by p53
expression in HepG2 but not in Hep3B despite upregulation of Bax protein in both
cell lines. Interestingly, p21 may be a remarkable switch to G1 arrest in HepG2
cells, but not in Hep3B cells. In addition, Fas- and mitochondria-mediated
pathways were found to be involved in MRE-induced apoptosis in Hep3B cells. The
GC-MS analysis of MRE revealed two major constituents of pharmaceutical
importance: the flavonoid apigenin (17.04%) and the terpenoid squalene (11.32%).
The data presented in this paper introduces G. bruguieri as a promising nontoxic
herb with therapeutic potential for HCC. To the authors' knowledge, the present
study provides the first report on the anticancer activity of MRE on HCC cells.
PMID- 28421124
TI - Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial
Dysfunction in Chronic Aristolochic Acid Nephropathy.
AB - Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD)
on chronic aristolochic acid nephropathy (AAN) in mice and its underlying
mechanisms were studied. Methods. Mice were randomly divided into the following
six groups: the control group, the model group (AAN), the saline-treated group
(AAN + vehicle), the normal dose DFD-treated group (AAN + NDFD), the high dose
DFD-treated group (AAN + HDFD), and the rosiglitazone treated group (AAN + Rosi).
After treating for 8 weeks, 24 h urine and blood samples were collected and the
mice sacrificed to study the biochemical parameters associated with renal
function. The samples were analyzed for renal fibrosis and mitochondrial
dysfunction (MtD) markers. To achieve that, collagen III, collagen I,
mitochondrial DNA copy numbers (mtDNA), mitochondrial membrane potential (MMP),
ATP content, and ROS production were evaluated. Results. Our results showed that
proteinuria, kidney function, and the renal pathological characteristics were
improved by DFD and rosiglitazone. The expression of collagen III and collagen I
decreased after treating with either DFD or rosiglitazone. Mitochondrial
dysfunction based on the increase in ROS production, decrease in mitochondrial
DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and
rosiglitazone. Conclusions. DFD could protect against renal impairments and
ameliorate mitochondrial dysfunction in chronic AAN mice.
PMID- 28421125
TI - Automatic Microaneurysms Detection Based on Multifeature Fusion Dictionary
Learning.
AB - Recently, microaneurysm (MA) detection has attracted a lot of attention in the
medical image processing community. Since MAs can be seen as the earliest lesions
in diabetic retinopathy, their detection plays a critical role in diabetic
retinopathy diagnosis. In this paper, we propose a novel MA detection approach
named multifeature fusion dictionary learning (MFFDL). The proposed method
consists of four steps: preprocessing, candidate extraction, multifeature
dictionary learning, and classification. The novelty of our proposed approach
lies in incorporating the semantic relationships among multifeatures and
dictionary learning into a unified framework for automatic detection of MAs. We
evaluate the proposed algorithm by comparing it with the state-of-the-art
approaches and the experimental results validate the effectiveness of our
algorithm.
PMID- 28421126
TI - Femoral Neck Strain during Maximal Contraction of Isolated Hip-Spanning Muscle
Groups.
AB - The aim of the study was to investigate femoral neck strain during maximal
isometric contraction of the hip-spanning muscles. The musculoskeletal and the
femur finite-element models from an elderly white woman were taken from earlier
studies. The hip-spanning muscles were grouped by function in six hip-spanning
muscle groups. The peak hip and knee moments in the model were matched to
corresponding published measurements of the hip and knee moments during maximal
isometric exercises about the hip and the knee in elderly participants. The
femoral neck strain was calculated using full activation of the agonist muscles
at fourteen physiological joint angles. The 5% +/- 0.8% of the femoral neck
volume exceeded the 90th percentile of the strain distribution across the 84
studied scenarios. Hip extensors, flexors, and abductors generated the highest
tension in the proximal neck (2727 MUepsilon), tension (986 MUepsilon) and
compression (-2818 MUepsilon) in the anterior and posterior neck, and compression
(-2069 MUepsilon) in the distal neck, respectively. Hip extensors and flexors
generated the highest neck strain per unit of joint moment (63-67 MUepsilon.m.N
1) at extreme hip angles. Therefore, femoral neck strain is heterogeneous and
muscle contraction and posture dependent.
PMID- 28421127
TI - Using Agent-Based Models to Develop Public Policy about Food Behaviours: Future
Directions and Recommendations.
AB - Most adults are overweight or obese in many western countries. Several population
level interventions on the physical, economical, political, or sociocultural
environment have thus attempted to achieve a healthier weight. These
interventions have involved different weight-related behaviours, such as food
behaviours. Agent-based models (ABMs) have the potential to help policymakers
evaluate food behaviour interventions from a systems perspective. However, fully
realizing this potential involves a complex procedure starting with obtaining and
analyzing data to populate the model and eventually identifying more efficient
cross-sectoral policies. Current procedures for ABMs of food behaviours are
mostly rooted in one technique, often ignore the food environment beyond home and
work, and underutilize rich datasets. In this paper, we address some of these
limitations to better support policymakers through two contributions. First, via
a scoping review, we highlight readily available datasets and techniques to deal
with these limitations independently. Second, we propose a three steps' process
to tackle all limitations together and discuss its use to develop future models
for food behaviours. We acknowledge that this integrated process is a leap
forward in ABMs. However, this long-term objective is well-worth addressing as it
can generate robust findings to effectively inform the design of food behaviour
interventions.
PMID- 28421128
TI - A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme
Cystathionine beta-Synthase: Increased CO Reactivity as a Novel Molecular
Mechanism of Pathogenicity?
AB - The human disease classical homocystinuria results from mutations in the gene
encoding the pyridoxal 5'-phosphate- (PLP-) dependent cystathionine beta-synthase
(CBS), a key enzyme in the transsulfuration pathway that controls homocysteine
levels, and is a major source of the signaling molecule hydrogen sulfide (H2S).
CBS activity, contributing to cellular redox homeostasis, is positively regulated
by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO* binding to
a noncatalytic heme moiety. Despite extensive studies, the molecular basis of
several pathogenic CBS mutations is not yet fully understood. Here we found that
the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral
properties and markedly increased affinity for CO, making the protein much more
prone than wild type (WT) CBS to inactivation at physiological CO levels. The
higher CO affinity could result from the slightly higher flexibility in the heme
surroundings revealed by solving at 2.80-A resolution the crystallographic
structure of a truncated p.P49L. Additionally, we report that p.P49L displays
impaired H2S-generating activity, fully rescued by PLP supplementation along the
purification, despite a minor responsiveness to AdoMet. Altogether, the results
highlight how increased propensity to CO inactivation of an otherwise WT-like
variant may represent a novel pathogenic mechanism in classical homocystinuria.
PMID- 28421129
TI - Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the
Heart.
AB - Background. Nitric oxide can successfully compete with oxygen for sites of
electron-transport chain in conditions of myocardial hypoxia. These features may
prevent excessive oxidative stress occurring in cardiomyocytes during sudden
hypoxia-reoxygenation. Aim. To study the action of the potent stable NO donor
dinitrosyl iron complex with glutathione (Oxacom(r)) on the recovery of
myocardial contractile function and Ca2+ transients in cardiomyocytes during
hypoxia-reoxygenation. Results. The isolated rat hearts were subjected to 30 min
hypoxia followed by 30 min reoxygenation. The presence of 30 nM Oxacom in hypoxic
perfusate reduced myocardial contracture and improved recovery of left
ventricular developed pressure partly due to elimination of cardiac arrhythmias.
The same Oxacom concentration limited reactive oxygen species generation in
hypoxic cardiomyocytes and increased the viability of isolated cardiomyocytes
during hypoxia from 12 to 52% and after reoxygenation from 0 to 40%. Oxacom
prevented hypoxia-induced elevation of diastolic Ca2+ level and eliminated Ca2+
transport alterations manifested by slow Ca2+ removal from the sarcoplasm and
delay in cardiomyocyte relaxation. Conclusion. The potent stable NO donor
preserved cardiomyocyte integrity and improved functional recovery at hypoxia
reoxygenation both in the isolated heart and in cardiomyocytes mainly due to
preservation of Ca2+ transport. Oxacom demonstrates potential for
cardioprotection during hypoxia-reoxygenation.
PMID- 28421130
TI - Antiretroviral Therapy Initiation Alters the Redox System of Asymptomatic HIV
Infected Individuals: A Longitudinal Study.
AB - Background. The combination antiretroviral therapy (cART) increases the oxidative
stress in HIV-infected people, which in turn favors the onset and aggravation of
non-AIDS comorbidities, a common situation affecting these individuals. We aimed
to evaluate the influence of cART initiation on oxidative stress parameters. This
is a longitudinal study including 30 asymptomatic patients divided according to
their CD4+ T cell count (G1: <500 cell/mL; G2: >500 cell/mL) before (M0) and
after (M1) cART initiation. We analyzed total antioxidant capacity (TAC), fat
soluble vitamins, malondialdehyde, 8-isoprostane, and DNA damage. Results.
Results showed a decrease in TAC, retinol, alpha-tocopherol, and some
carotenoids, in addition to a significant increase in DNA damage at M1. These
changes were more evident in G2 subjects. Moreover, there was a significant 8
isoprostane increase at M1 in individuals belonging to G1. Conclusion. The
results indicate that cART interfered in the redox system, mainly by reducing the
antioxidant defenses. In addition, patients who had CD4+ T counts higher than 500
cells/mm3 showed more susceptibility to genotoxicity, while patients with less
CD4+ T counts displayed more damage triggered by lipoperoxidation. Considering
the early beginning of cART, its chronic use, and its capacity to alter the redox
status, further long-term studies on larger cohorts are needed to define the best
time to initiate therapy and to investigate new strategies to delay the
development of non-AIDS diseases.
PMID- 28413608
TI - Evidence synthesis and decision modelling to support complex decisions:
stockpiling neuraminidase inhibitors for pandemic influenza usage.
AB - Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a
defence against pandemic influenza is a significant public health policy decision
that must be made despite a lack of conclusive evidence from randomised
controlled trials regarding the effectiveness of NAIs on important clinical end
points such as mortality. The objective of this study was to determine whether
NAIs should be stockpiled for treatment of pandemic influenza on the basis of
current evidence. Methods: A decision model for stockpiling was designed. Data on
previous pandemic influenza epidemiology was combined with data on the
effectiveness of NAIs in reducing mortality obtained from a recent individual
participant meta-analysis using observational data. Evidence synthesis techniques
and a bias modelling method for observational data were used to incorporate the
evidence into the model. The stockpiling decision was modelled for adults (>=16
years old) and the United Kingdom was used as an example. The main outcome was
the expected net benefits of stockpiling in monetary terms. Health benefits were
estimated from deaths averted through stockpiling. Results: After adjusting for
biases in the estimated effectiveness of NAIs, the expected net benefit of
stockpiling in the baseline analysis was L444 million, assuming a willingness to
pay of L20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile
NAIs. There was a greater probability that the stockpile would not be utilised
than utilised. However, the rare but catastrophic losses from a severe pandemic
justified the decision to stockpile. Conclusions: Taking into account the
available epidemiological data and evidence of effectiveness of NAIs in reducing
mortality, including potential biases, a decision maker should stockpile anti
influenza medication in keeping with the postulated decision rule.
PMID- 28413610
TI - Animating and exploring phylogenies with fibre plots.
AB - Despite the progress that has been made in the visualisation of information since
Haeckel's time, phylogenetic visualisation has moved forward remarkably little.
In this brief essay, I give a short review of what I consider to be some recent
major advances, and outline a new kind of phylogenetic visualisation. This new
graphic, the fibre plot, uses the metaphor of sections through a tree to describe
change in a phylogeny. As an animation, I suggest it is a powerful method to help
interpret large phylogenetic hypotheses, although snapshots of it can also be
displayed. As we enter the Anthropocene, I argue there has never been a greater
need to know humanity's true place in the world, as depicted in the tree of life.
PMID- 28413610
TI - Animating and exploring phylogenies with fibre plots.
AB - Despite the progress that has been made in many other aspects of data
visualisation, phylogenies are still represented in much the same way as they
first were by Darwin. In this brief essay, I give a short review of what I
consider to be some recent major advances, and outline a new kind of phylogenetic
visualisation. This new graphic, the fibre plot, uses the metaphor of sections
through a tree to describe change in a phylogeny. I suggest it is a useful tool
in gaining an rapid overview of the timing and scale of diversification in large
phylogenies.
PMID- 28413615
TI - Mean Platelet Volume (MPV) as an indicator of disease activity and severity in
lupus.
AB - Background: Amongst the different clinical and laboratory parameters used to
monitor disease activity in systemic lupus erythematosus (SLE), mean platelet
volume (MPV) is a novel biomarker. Although MPV has been studied in other
rheumatological conditions like rheumatoid arthritis, its role in adult SLE needs
to be defined, especially in Pakistan. Methods: The aim of this study was to
evaluate the role of MPV as a biomarker of disease activity in SLE. Fifty
patients were recruited through a consecutive non-probability sampling technique
for this cross-sectional study. On the basis of their SLE disease activity index
(SLEDAI) score of greater or lesser than 5, these 50 participants were divided
into two equal groups respectively;25 patients with active SLE, and another 25
participants with stable, inactive lupus. MPV was measured in each group and
compared using SPSS version 16. MPV was also correlated with SLEDAI and
erythrocyte sedimentation rate (ESR). Independent sample t-test and Pearson's
correlation tests were applied. Sensitivity and specificity of MPV were checked
through ROC analysis. Results: The MPV of patients with active SLE (n=25, mean
[M]=7.12, SD=1.01) was numerically lower than those in the inactive-SLE group
(n=25, M= 10.12, SD=0.97), and this was statistically significant ( P<0.001). MPV
had an inverse relationship with both ESR (r=-0.93, P<0.001) and SLEDAI (r=
0.94, P<0.001). However, there was a strong positive correlation between ESR and
SLEDAI (r=0.95, P<0.001). For MPV, a cutoff value of less than 8.5fl had a
sensitivity of 92% and a specificity of 100% ( P< 0.001). Conclusions: Higher
disease activity in SLE is associated with a correspondingly low MPV.
PMID- 28413615
TI - Mean Platelet Volume (MPV) as an indicator of disease activity and severity in
lupus.
AB - Background: Amongst the different clinical and laboratory parameters used to
monitor disease activity in systemic lupus erythematosus (SLE), mean platelet
volume (MPV) is a novel biomarker. Although MPV has been studied in other
rheumatological conditions like rheumatoid arthritis, its role in adult SLE needs
to be defined, especially in Pakistan. Methods: The aim of this study was to
evaluate the role of MPV as a biomarker of disease activity in SLE. Fifty
patients were recruited through a consecutive non-probability sampling technique
for this cross-sectional study. On the basis of their SLE disease activity index
(SLEDAI) score of greater or lesser than 5, these 50 participants were divided
into two equal groups respectively;25 patients with active SLE, and another 25
participants with stable, inactive lupus. MPV was measured in each group and
compared using SPSS version 16. MPV was also correlated with SLEDAI and
erythrocyte sedimentation rate (ESR). Independent sample t-test and Spearman's
rho and Pearson's correlation tests were applied. Sensitivity and specificity of
MPV were checked through ROC analysis. Results: The MPV of patients with
active SLE (n=25, mean [M]=7.12, SD=1.01) was numerically lower than those in the
inactive-SLE group (n=25, M= 10.12, SD=0.97), and this was statistically
significant ( P<0.001). MPV had an inverse relationship with both ESR (r=-0.93,
P<0.001) and SLEDAI (r s= -0.89, P<0.001). However, there was a strong positive
correlation between ESR and SLEDAI (r s=0.90, P<0.001). For MPV, a cutoff value
of less than 8.5fl had a sensitivity of 92% and a specificity of 100% ( P<
0.001). Conclusions: Higher disease activity in SLE is associated with a
correspondingly low MPV.
PMID- 28421136
TI - Time from pre-eclampsia diagnosis to delivery affects future health prospects of
children.
AB - Background and objectives: Pre-eclampsia often has detrimental health effects for
pregnant women and their fetuses, but whether exposure in the womb has long-term
health-consequences for children as they grow up remains poorly understood. We
assessed overall morbidity of children following exposure to either mild or
severe pre-eclampsia up to 30 years after birth and related disease risks to
duration of exposure, i.e. the time from diagnosis to delivery. Methodology: We
did a registry-based retrospective cohort study in Denmark covering the years
1979-2009, using the separate diagnoses of mild and severe pre-eclampsia and the
duration of exposure as predictor variables for specific and overall risks of
later disease. We analysed 3 537 525 diagnoses for 14 disease groups, accumulated
by 758 524 singleton children, after subdividing deliveries in six gestational
age categories, partialing out effects of eight potentially confounding factors.
Results: Exposure to mild pre-eclampsia appeared to have consistent negative
effects on health later in life, although only a few specific disease cases
remained significant after corrections for multiple testing. Morbidity risks
associated with mild pre-eclampsia were of similar magnitude as those associated
with severe pre-eclampsia. Apart from this overall trend in number of diagnoses
incurred across disease groups, hazard ratios for several disorders also
increased with the duration of exposure, including disorders related to the
metabolic syndrome. Conclusions and implications: Maternal pre-eclampsia has
lasting effects on offspring health and differences between exposure to severe
and mild pre-eclampsia appear to be less than previously assumed. Our results
suggest that it would be prudent to include the long-term health prospects of
children in the complex clinical management of mild pre-eclampsia.
PMID- 28421137
TI - The effect of temperature on development and behaviour of relict leopard frog
tadpoles.
AB - Relict leopard frog (Rana [Lithobates] onca) tadpoles were obtained shortly after
hatching at Gosner stage 25 and raised in aquaria maintained at 15, 20, 25, 30
and 35 degrees C. Development was arrested in the 15 degrees C group, and
survivorship declined to 64% after 191 days. However, 80% of the surviving larvae
remained alive after the temperature was increased to 25 degrees C. Of these, 96%
reached metamorphosis. Survivorship of the 20, 25 and 30 degrees C acclimation
groups was 82, 94 and 66%, respectively, whereas none survived at 35 degrees C.
Time to metamorphosis was significantly shorter for the 25 degrees C group (67 +/
1 days), followed by the 30 degrees C (98 +/- 2 days) and 20 degrees C (264 +/-
7 days) groups. A linear 66 cm thermal gradient was used to identify temperature
ranges selected by tadpoles in the different acclimation groups. Five 10 degrees
C gradients (10-20, 15-25, 20-30, 25-35 and 30-40 degrees C) were used, and time
spent in the cooler, middle and warmer thirds of the gradient was compared for 10
individuals from each acclimation group. In the coolest gradient, tadpoles from
all acclimation groups selected the warmer third (>17 degrees C) of the gradient.
In the warmer gradients, tadpoles from the 20 and 25 degrees C acclimation groups
selected temperatures <29 degrees C, while those from the 30 degrees C
acclimation group selected temperatures <33 degrees C. Maximal burst speed for
all groups was greater at experimental temperatures of 25 than 15 degrees C.
Efforts to reintroduce this species to its historical range should select
habitats where water temperatures between 25 and 30 degrees C are available
during the post-hatching period.
PMID- 28421138
TI - Habitat disturbance results in chronic stress and impaired health status in
forest-dwelling paleotropical bats.
AB - Anthropogenic habitat disturbance is a major threat to biodiversity worldwide.
Yet, before population declines are detectable, individuals may suffer from
chronic stress and impaired immunity in disturbed habitats, making them more
susceptible to pathogens and adverse weather conditions. Here, we tested in a
paleotropical forest with ongoing logging and fragmentation, whether habitat
disturbance influences the body mass and immunity of bats. We measured and
compared body mass, chronic stress (indicated by neutrophil to lymphocyte ratios)
and the number of circulating immune cells between several bat species with
different roost types living in recovering areas, actively logged forests, and
fragmented forests in Sabah, Malaysia. In a cave-roosting species, chronic stress
levels were higher in individuals from fragmented habitats compared with
conspecifics from actively logged areas. Foliage-roosting species showed a
reduced body mass and decrease in total white blood cell counts in actively
logged areas and fragmented forests compared with conspecifics living in
recovering habitats. Our study highlights that habitat disturbance may have
species-specific effects on chronic stress and immunity in bats that are
potentially related to the roost type. We identified foliage-roosting species as
particularly sensitive to forest habitat deterioration. These species may face a
heightened extinction risk in the near future if anthropogenic habitat
alterations continue.
PMID- 28421139
TI - Regional Relationship between Macular Retinal Thickness and Corresponding Central
Visual Field Sensitivity in Glaucoma Patients.
AB - Purpose. To investigate the relationship between macular retinal thickness (MRT)
and central visual field sensitivity (VFS) in patients with glaucoma. Methods.
This retrospective study enrolled patients diagnosed with open-angle glaucoma.
All study patients underwent Humphrey 10-2 visual field (VF) test and Spectralis
spectral-domain optical coherence tomography (SD-OCT) exam for MRT measurement.
Results. Sixty-eight eyes of 68 patients were examined. The correlation
coefficients between VFS and MRT were 0.331 (P = 0.006) and 0.491 (P = 0.000) in
the superior and inferior hemispheres, respectively. The average MRT in the eyes
with abnormal 10-2 VF hemifields was significantly thinner than that in the eyes
without abnormal hemifields in both hemispheres (P = 0.005 and 0.000 in the
superior and inferior hemisphere, resp.). The average MRT values with an optimal
sensitivity-specificity balance for discriminating the abnormal VF hemifield from
the normal hemifield were 273.5 MUm and 255.5 MUm in the superior and inferior
hemisphere, respectively. The area under the receiver operating characteristic
curve was 0.701 in the superior hemisphere and 0.784 in the inferior hemisphere
(both P < 0.05). Conclusions. MRT measured through SD-OCT was significantly
correlated with central VFS. Lower MRT values might be a warning sign for central
VF defects in glaucoma patients.
PMID- 28421140
TI - Comparison of Corneal Power and Astigmatism between Simulated Keratometry, True
Net Power, and Total Corneal Refractive Power before and after SMILE Surgery.
AB - Purpose. To compare the mean corneal power (Km) and total astigmatism (Ka)
estimated by three methods: simulated keratometry (simK), true net power (TNP),
and total corneal refractive power (TCRP) before and after femtosecond laser
small incision lenticule extraction (SMILE) surgery. Methods. A retrospective,
cross-sectional study. SimK, TNP, and TCRP from a Scheimpflug analyzer were
obtained from 144 patients before and 6 months after SMILE surgery. Km and Ka
were recorded as the mean of individual paracentral rings of 1.0 to 8.0 mm (R1 to
R8). The surgically induced changes in Km (delta-simK, delta-TNP, and delta-TCRP)
and Ka (delta-simKa, delta-TNPa, and delta-TCRPa) were compared to the changes in
spherical equivalent of the cycloplegic refraction (delta-SE) and astigmatism
(delta-RA). Results. Preoperatively, astigmatism values were greatest with simKa
from R1 to R5 and greatest with TCRPa from R6 to R8. Astigmatism values were
smallest with TNPa from R1 to R7. Postoperatively, astigmatism values were
greatest with simKa from R1 to R5 and greatest with TCRPa from R6 to R8. Delta
TCRP3 and Delta-TCRP4 matched delta-SE most closely, and delta-TCRPa3 matched
delta-RA most closely. Conclusions. TCRP proved to be the most accurate method in
estimating corneal power and astigmatism both before and after SMILE surgery.
PMID- 28421141
TI - Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the
Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect.
AB - Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related
peptides. In the brain, it activates the renin angiotensin system and causes
hypertension. Limited data are available on the dipsogenic effect of APA and
pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats
received intracerebroventricular (icv) APA in a conscious, unrestrained state
after pretreatment with (i) vehicle, (ii) 80 MUg of telmisartan, an Ang II type-1
(AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor,
and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration
of 400 and 800 ng of APA increased blood pressure by 12.6 +/- 3.0 and 19.0 +/-
3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to
APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 +/- 2.2 mmHg
versus telmisartan: 10.4 +/- 3.2 mmHg). Pressor response to APA was also
attenuated with amastatin and HOE-140 (vehicle: 26.5 +/- 1.1 mmHg, amastatin:
14.4 +/- 4.2 mmHg, HOE-140: 16.4 +/- 2.2 mmHg). In conclusion, APA increase in
the brain evokes a pressor response via enzymatic activity without dipsogenic
effect. AT1 receptors and B2 receptors in the brain may contribute to the APA
induced pressor response.
PMID- 28421142
TI - Plackett-Burman Design for rGILCC1 Laccase Activity Enhancement in Pichia
pastoris: Concentrated Enzyme Kinetic Characterization.
AB - Laccases are multicopper oxidases that catalyze aromatic and nonaromatic
compounds with concomitant reduction of molecular oxygen to water. They are of
great interest due to their potential biotechnological applications. In this work
we statistically improved culture media for recombinant GILCC1 (rGILCC1) laccase
production at low scale from Ganoderma lucidum containing the construct
pGAPZalphaA-GlucPost-Stop in Pichia pastoris. Temperature, pH stability, and
kinetic parameter characterizations were determined by monitoring concentrate
enzyme oxidation at different ABTS substrate concentrations. Plackett-Burman
Design allowed improving enzyme activity from previous work 36.08-fold, with a
laccase activity of 4.69 +/- 0.39 UL-1 at 168 h of culture in a 500 mL shake
flask. Concentrated rGILCC1 remained stable between 10 and 50 degrees C and
retained a residual enzymatic activity greater than 70% at 60 degrees C and 50%
at 70 degrees C. In regard to pH stability, concentrated enzyme was more stable
at pH 4.0 +/- 0.2 with a residual activity greater than 90%. The lowest residual
activity greater than 55% was obtained at pH 10.0 +/- 0.2. Furthermore,
calculated apparent enzyme kinetic parameters were a Vmax of 6.87 * 10-5 mM s-1,
with an apparent Km of 5.36 * 10-2 mM. Collectively, these important stability
findings open possibilities for applications involving a wide pH and temperature
ranges.
PMID- 28421143
TI - The Dual Burden of Malnutrition and Associated Dietary and Lifestyle Habits among
Lebanese School Age Children Living in Orphanages in North Lebanon.
AB - Childhood is a crucial period affecting physical and intellectual development.
Although children living in orphanages are among the most vulnerable groups at
risk of malnutrition, there is scarcity of data concerning their nutritional
status in Lebanon. To investigate these data, a cross-sectional survey was
conducted including a sample of 153 institutionalized children aged 5-14 years
from all orphanages in Tripoli. Nutritional status was assessed using
anthropometric, clinical, and dietary tools. Interpretation of anthropometric
data showed that 13.8% were stunted while the prevalence of overweight/obesity
was 9.2% according to the World Health Organization (WHO) reference criteria.
Physical signs suggesting nutritional deficiencies were detected in about 25% of
the sample. Dietary intake evaluation showed that about half of the participants
had inadequate dietary intakes of proteins, fruits, and vegetables and 92% had
inadequate milk and dairy intakes recommended for their age specific needs.
Multivariate regression analysis revealed statistically significant positive
association of age, skipping breakfast, and increased screen time with stunting
while it showed statistically significant negative association of inadequate
protein intake with overweight/obesity. The coexistence of under- and
overnutrition among institutionalized children calls for implementation of
comprehensive intervention strategies committed to reducing undernutrition while
simultaneously preventing overnutrition through improving diet quality and
physical activity of these children.
PMID- 28421144
TI - Prevalence of Sarcopenic Obesity in Adults with Class II/III Obesity Using
Different Diagnostic Criteria.
AB - Background/Objective. Sarcopenic obesity (SO) is a hidden condition of reduced
lean soft tissue (LST) in context of excess adiposity. SO is most commonly
reported in older adults and both its risk and prevalence increase with age. A
variety of body composition indices and cut points have been used to define this
condition, leading to conflicting prevalence and risk prediction. Here, we
investigate variability in the prevalence of SO in an adult sample of individuals
with class II/III obesity (BMI >= 35 kg/m2) using different diagnostic criteria.
Methods. SO definitions were identified from a literature review of studies using
dual-energy X-ray absorptiometry (DXA) to assess LST. Demographics,
anthropometrics, and body composition (by DXA) were measured in n = 120, 86%
female (46.9 +/- 11.1 years). Results. LST was extremely variable in individuals,
even with similar body sizes, and observed across the age spectrum. The
prevalence of SO ranged from 0 to 84.5% in females and 0 to 100% in males,
depending upon the definition applied, with higher prevalence among definitions
accounting for measures of body size or fat mass. Conclusion. SO is present, yet
variable, in adults with class II/III obesity. Accounting for body mass or fat
mass may identify a higher number of individuals with SO, although risk
prediction remains to be studied.
PMID- 28421145
TI - A Framework for Describing the Influence of Service Organisation and Delivery on
Participation in Fetal Anomaly Screening in England.
AB - Objective. The aim of this research was to explore the influence of service
organisation and delivery on providers and users' interactions and decision
making in the context of Down's syndrome screening. Methods. A qualitative
descriptive study involving online interviews conducted with a purposive sample
of 34 community midwives, 35 pregnant women, and 15 partners from two maternity
services in different health districts in England. Data were analysed using a
combination of grounded theory principles and content analysis and a framework
was developed. Results. The main emerging concepts were organisational
constraints, power, routinisation, and tensions. Providers were concerned about
being time-limited that encouraged routine, minimal information-giving and lacked
skills to check users' understanding. Users reported their participation was
influenced by providers' attitudes, the ambience of the environment, asymmetric
power relations, and the offer and perception of screening as a routine test.
Discordance between the national programme's policy of nondirective informed
choice and providers' actions of recommending and arranging screening
appointments was unexpected. Additionally, providers and users differing
perceptions of emotional effects of information, beliefs, and expectations
created tensions within them, between them, and in the antenatal environment.
Conclusions. A move towards a social model of care may be beneficial to empower
service users and create less tension for providers and users.
PMID- 28421146
TI - Breastfeeding after Gestational Diabetes: Does Perceived Benefits Mediate the
Relationship?
AB - Introduction. Breastfeeding is recognized as one of the best ways to decrease
infant mortality and morbidity. However, women with gestational diabetes mellitus
(GDM) may have breastfeeding barriers due to the increased risk of neonatal and
pregnancy complications. While the prevalence of GDM is increasing worldwide, it
is important to understand the full implications of GDM on breastfeeding
outcomes. The current study aims to investigate the (1) direct effect of GDM on
breastfeeding duration and (2) indirect effect of GDM on breastfeeding duration
through perceived benefits of breastfeeding. Methods. Prospective cohort data
from the Infant Feeding and Practices Study II was analyzed (N = 4,902).
Structural equation modeling estimated direct and indirect effects. Results.
Perceived benefits of breastfeeding directly influenced breastfeeding duration
(beta = 0.392, p <= 0.001). GDM was not directly associated with breastfeeding
duration or perceived benefits of breastfeeding. Similarly, GDM did not have an
indirect effect on breastfeeding duration through perceived benefits of
breastfeeding. Conclusions. Perceived benefits of breastfeeding are an important
factor associated with breastfeeding duration. Maternal and child health care
professionals should enhance breastfeeding education efforts.
PMID- 28421147
TI - Electrophysiological, Morphological, and Ultrastructural Features of the Injured
Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood
Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.
AB - In this study, we examined the efficacy of human umbilical cord blood mononuclear
cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using
adenoviral vectors, on posttraumatic regeneration after transplantation into the
site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by
transplantation of nontransduced hUCB-MCs, we observed an improvement in H
(latency period, LP) and M(Amax) waves, compared to the group without therapy
after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M
wave and LP of both the M and H waves. The ratio between Amax of the H and M
waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of
genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs.
Spared tissue and myelinated fibers were increased at day 30 after SCI and
transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the
lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF
and GNDF genes significantly increased the number of spared myelinated fibers (22
fold, P > 0.01) in the main corticospinal tract compared to the nontransduced
ones. HNA+ cells with the morphology of phagocytes and microglia-like cells were
found as compact clusters or cell bridges within the traumatic cavities that were
lined by GFAP+ host astrocytes. Our results show that hUCB-MCs transplanted into
the site of SCI improved regeneration and that hUCB-MCs genetically modified with
the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.
PMID- 28421148
TI - Multidisciplinary Approach in the Management of a Complex Case: Implant
Prosthetic Rehabilitation of a Periodontal Smoking Patient with Partial
Edentulism, Malocclusion, and Aesthetic Diseases.
AB - Complex periprosthetic cases are considered as challenges by clinicians. Clinical
and radiographic parameters should be considered separately to make the right
choice between an endodontically or periodontally compromised treated tooth and
implant. Therefore, in order to decide whether the tooth is safe or not, data
that have to be collected are specific parameters of both the patient and the
clinician. In addition, the presence of periodontal, prosthetic, and orthodontic
diseases requires patients to be set in multidisciplinary approach. The aim of
this case report is to describe how the multidisciplinary approach could be the
best way to manage difficult cases of implant-prosthetic rehabilitation. How to
rehabilitate with fixed prosthesis on natural teeth and dental implants a smoker
patient who presents with active periodontitis, multiple edentulous areas, dental
malocclusion, and severe aesthetic problems was also described.
PMID- 28421149
TI - Eccrine Nevus Presenting with Umbilical Discharge: A Case Report and Review of
the Literature.
AB - Eccrine nevus is a rare skin lesion with protean manifestations like
hyperhidrosis, discolored nodules, papules, and so forth, which has been reported
in various anatomic parts of the body including the forearm, leg, thigh, back,
and coccyx. Our patient was a 26-year-old male, who presented with increasing
colorless and odorless episodic umbilical discharge. First impression for the
patient was an umbilical sinus and the patient underwent surgery.
Histopathological study revealed the lesion to be an eccrine nevus of the
umbilicus. This is the first case of eccrine nevus presenting with umbilical
discharge. We recommend that eccrine nevus should be considered as a differential
diagnosis for umbilical discharge.
PMID- 28421150
TI - Post-ERCP Emphysematous Cholecystitis in a Young Woman: A Rare and Potentially
Fatal Complication.
AB - A 45-year-old woman with suspected Functional Biliary Sphincter Disorder (FBSD)
developed Clostridium perfringens related emphysematous cholecystitis after ERCP.
A low index of suspicion for emphysematous cholecystitis in this young, otherwise
healthy woman led to a significant delay in making the correct diagnosis, and air
in the gallbladder was wrongly attributed to a possible gallbladder perforation.
ERCP is associated with significant risks, particularly in patients with FBSD,
where diagnostic uncertainty renders the balance of risk versus benefit even more
critical. Post-ERCP emphysematous cholecystitis secondary to Clostridium
perfringens is a rare but potentially fatal complication.
PMID- 28421151
TI - Extramedullary Relapse in a CML Patient after Allogeneic Stem Cell
Transplantation.
AB - Myeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature
granulocytic cells. It is a rare entity during the course of CML patients
especially after allogeneic stem cell transplantation (SCT). Relapse without bone
marrow involvement is much rarer. We report a case of CML patient who relapsed
with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and
molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was
performed because of refractory disease to tyrosine kinase inhibitors. Complete
cytogenetic and molecular response was achieved after allogeneic SCT followed by
dasatinib treatment. Approximately 5 years after the transplantation, very
rapidly progressive lesion was documented and diagnosed as GS although he was at
molecular and cytogenetic remission. The patient died during chemotherapy due to
sepsis. GS relapse after allogeneic SCT is a very rare type of relapse in CML
patients with molecular and cytogenetic remission. Since it is a very aggressive
disease with a poor prognosis, combined chemoradiotherapies with other possible
options like DLI or second allogeneic SCT should be considered as soon as the
diagnosis is confirmed.
PMID- 28421152
TI - Spontaneous Adrenal Hemorrhage in Pregnancy: A Case Series.
AB - Background. Abdominal pain during pregnancy has a broad differential diagnosis
which includes spontaneous adrenal hemorrhage (SAH). There is scant literature
available on optimal mode of delivery in stable patients. Cases. Patient 1 was a
35-year-old nullipara who presented at 36 weeks of gestation with left flank
pain. Patient 2 was a 27-year-old multipara at 38 weeks who presented with left
upper quadrant pain. Diagnosis of SAH was made by CT scan and both were managed
with pain control, serial hemoglobin assessments, and abdominal exams resulting
in uncomplicated vaginal deliveries. Conclusion. SAH, although rare, is an
important consideration when evaluating abdominal and flank pain in pregnancy.
Management options vary from conservative management to surgical intervention
depending on the stability of the patient.
PMID- 28421153
TI - Breast Cancer Suspicion in a Transgender Male-to-Female Patient on Hormone
Replacement Therapy Presenting with Right Breast Mass: Breast Cancer Risk
Assessment and Presentation of a Rare Lesion.
AB - There has been an increasing use of hormonal therapy among male-to-female (MtF)
transgender individuals. This long-term hormone replacement therapy (HRT) renders
MtF individuals a unique patient subgroup in terms of breast cancer risk. This
case describes a MtF transgender who presented with a breast lesion concerning
for malignancy following hormonal replacement therapy. The patient additionally
had a strong family history of breast cancer. Final pathology revealed lobular
hyperplasia in the setting of gynecomastia and pseudoangiomatous stromal
hyperplasia (PASH). Both pathology findings are rare in biological females, let
alone in the setting of hormone replacement therapy in a MtF individual. While
the number of reported cases of suspicious breast lesions in this population
remains scarce, it presents both a diagnostic and therapeutic challenge due to
the nature of the treatment course and the lack of research in this recently
growing subgroup of patients.
PMID- 28421154
TI - Aggressive Digital Papillary Adenocarcinoma of the Hand Presenting as a Felon.
AB - Aggressive digital papillary adenocarcinoma is a rare eccrine sweat gland
malignancy that is frequently misdiagnosed at initial presentation.
Histologically, this tumor is similar in appearance to many adenocarcinomas and
as such may be diagnosed as a metastatic lesion. We present the case of a patient
with digital papillary adenocarcinoma, which was initially diagnosed as a felon.
No consensus has been published regarding the treatment of this disease. A review
of the diagnosis, pathology, treatment, and adjunctive treatments of aggressive
digital papillary adenocarcinoma are also included.
PMID- 28421155
TI - An Appendiceal Carcinoid Tumor within an Amyand's Hernia Mimicking an
Incarcerated Inguinal Hernia.
AB - Introduction. We report the case of an appendiceal carcinoid tumor within an
Amyand's hernia, presenting as an incarcerated right inguinal hernia.
Presentation of Case. A 52-year-old male presented in the emergency department
due to a persistent right inguinal pain. Clinical examination revealed a tender
right groin mass. Laboratory tests revealed leukocytosis and an increased serum
CRP. Under the diagnosis of an incarcerated right inguinal hernia, an emergency
operation was taken. Intraoperatively, an inflamed appendix and a part of the
cecum were found in the hernia sac. The operation was completed with an
appendectomy and a modified Bassini hernia repair. Histological examination
revealed a carcinoid tumor, resulting in the performance of a right
hemicolectomy. Discussion. Amyand's hernia is estimated to account for 0.4% to
0.6% of all inguinal hernias. Coexistence of an Amyand's hernia and a neoplasia
is quite rare. Carcinoids are the most frequent tumors found in the appendix,
with the size of the primary tumor to be considered the most important prognostic
factor and the basis upon which the operative plan is decided. Conclusion. A
malignancy of the appendix should always be in the differential diagnosis of a
right inguinal mass, in order to provide optimum surgical treatment.
PMID- 28421157
TI - Psoriatic Arthritis Is an Indicator of Significant Renal Damage in Patients with
Psoriasis: An Observational and Epidemiological Study.
AB - Background. Psoriasis affects joints in around 30% of the patients. Recent
studies have demonstrated an increased risk of essential hypertension, ischemic
heart disease, and stroke in psoriatic patients. However, the prevalence of renal
disease in patients with psoriasis has not been evaluated properly. Objectives.
Objectives were to evaluate renal functions in patients with psoriasis and to
assess any possible relationship of renal failure with psoriasis and psoriatic
arthritis. Methods. In this cross-sectional study, 30 participants were recruited
into the following three groups: group-A, psoriatic arthritis; group-B, psoriasis
without arthritis; and group-C, healthy subjects. Renal function tests were
performed for every participant of each group. The data was analyzed by using
SPSS version 16. Chi-squared and one-way ANOVA tests were applied, considering a
P value of less than 0.05 as a standard criterion. Results. Serum creatinine,
urea, and phosphate were the highest in group-A, higher in group-B, and normal in
group-C, P < 0.05. Similarly, GFR was the lowest in group-A, lower in group-B,
and normal in group-C. The difference in mean GFR values was statistically
significant, F(2) = 355, P < 0.001. Moreover, proteinuria (gm/day) was seen in
96.7% of the patients with psoriatic arthritis, (M = 1.18 +/- 0.55, P < 0.05)
against 10% of the psoriatic patients without arthritis (M = 0.41 +/- 0.10, P <
0.05). Conclusion. Derangement of renal function is more prevalent in psoriatic
patients, especially in those with concomitant psoriatic arthritis. Therefore,
each psoriatic patient must be routinely screened for an underlying renal
failure.
PMID- 28421156
TI - The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative
Pharmacogenetics and Pharmacometabolomics.
AB - Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients
undergoing percutaneous coronary intervention. However, the variable platelets
reactivity response to clopidogrel may lead to outcome failure and recurrence of
cardiovascular events. Although many genetic and nongenetic factors are known,
great portion of clopidogrel variable platelets reactivity remain unexplained
which challenges the personalization of clopidogrel therapy. Current methods for
clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and
platelets function testing. However, these methods lack precise prediction of
clopidogrel outcome, often leading to insufficient prediction.
Pharmacometabolomics which is an approach to identify novel biomarkers of drug
response or toxicity in biofluids has been investigated to predict drug response.
The advantage of pharmacometabolomics is that it does not only predict the
response but also provide extensive information on the metabolic pathways
implicated with the response. Integrating pharmacogenetics with
pharmacometabolomics can give insight on unknown genetic and nongenetic factors
associated with the response. This review aimed to review the literature on
factors associated with the variable platelets reactivity response to
clopidogrel, as well as appraising current methods for the personalization of
clopidogrel therapy. We also aimed to review the literature on using
pharmacometabolomics approach to predict drug response, as well as discussing the
plausibility of using it to predict clopidogrel outcome.
PMID- 28421158
TI - Cytotoxicity of Zardaverine in Embryonal Rhabdomyosarcoma from a Costello
Syndrome Patient.
AB - Costello syndrome (CS) patients suffer from a very high 10% incidence of
embryonal rhabdomyosarcoma (ERMS). As tools to discover targeted therapeutic
leads, we used a CS patient-derived ERMS cell line (CS242 ERMS) harboring a
homozygous p.G12A mutation in HRAS, and a control cell line derived from the same
patient comprising non-malignant CS242 fibroblasts with a heterozygous p.G12A
HRAS mutation. A library of 2,000 compounds with known pharmacological activities
was screened for their effect on CS242 ERMS cell viability. Follow-up testing in
a panel of cell lines revealed that various compounds originally developed for
other indications were remarkably selective; notably, the phosphodiesterase (PDE)
inhibitor zardaverine was at least 1,000-fold more potent in CS242 ERMS than in
the patient-matched non-malignant CS242 fibroblasts, other ERMS, or normal
fibroblasts. Chronic treatment with zardaverine led to the emergence of resistant
cells, consistent with CS242 ERMS comprising a mixed population of cells. Many
PDE inhibitors in addition to zardaverine were tested on CS242 ERMS, but almost
all had no effect. Interestingly, zardaverine and analogs showed a similar
cytotoxicity profile in CS242 ERMS and cervical carcinoma-derived HeLa cells,
suggesting a mechanism of action common to both cell types that does not require
the presence of an HRAS mutation (HeLa contains wild type HRAS). Two recent
studies presented possible mechanistic explanations for the cytotoxicity of
zardaverine in HeLa cells. One revealed that zardaverine inhibited a HeLa cell
based screen measuring glucocorticoid receptor (GR) activation; however, using
engineered HeLa cells, we ruled out a specific effect of zardaverine on signaling
through the GR. The second attributed zardaverine toxicity in HeLa cells to
promotion of the interaction of phosphodiesterase 3A and the growth regulatory
protein Schlafen 12. We speculate that this work may provide a possible mechanism
for zardaverine action in CS242 ERMS, although we have not yet tested this
hypothesis. In conclusion, we have identified zardaverine as a potent cytotoxic
agent in a CS-derived ERMS cell line and in HeLa. Although we have ruled out some
possibilities, the mechanism of action of zardaverine in CS242 ERMS remains to be
determined.
PMID- 28421159
TI - Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic
Reprogramming.
AB - Tumor cells reprogram their metabolism to survive and grow in a challenging
microenvironment. Some of this reprogramming is performed by epigenetic
mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying
enzymes are dependent on substrates that are also key metabolic intermediates. We
have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an
epigenetic regulator, is necessary for rapid breast cancer cell proliferation.
The mechanism for this requirement is the BRG1-dependent transcription of key
lipogenic enzymes and regulators. Reduction in lipid synthesis lowers
proliferation rates, which can be restored by palmitate supplementation. This
work has established BRG1 as an attractive target for breast cancer therapy.
Unlike genetic alterations, epigenetic mechanisms are reversible, promising
gentler therapies without permanent off-target effects at distant sites.
PMID- 28421160
TI - The Unfolded Protein Response: At the Intersection between Endoplasmic Reticulum
Function and Mitochondrial Bioenergetics.
AB - Endoplasmic reticulum (ER) to mitochondria communication has emerged in recent
years as a signaling hub regulating cellular physiology with a relevant
contribution to diseases including cancer and neurodegeneration. This functional
integration is exerted through discrete interorganelle structures known as
mitochondria-associated membranes (MAMs). At these domains, ER/mitochondria
physically associate to dynamically adjust metabolic demands and the response to
stress stimuli. Here, we provide a focused overview of how the ER shapes the
function of the mitochondria, giving a special emphasis to the significance of
local signaling of the unfolded protein response at MAMs. The implications to
cell fate control and the progression of cancer are also discussed.
PMID- 28421161
TI - Incidence of Immune-Related Adverse Events with Program Death Receptor-1- and
Program Death Receptor-1 Ligand-Directed Therapies in Genitourinary Cancers.
AB - Program death receptor-1 (PD-1) and program death receptor-1 ligand (PD-L1)
inhibitors are increasingly being used in the clinic to treat a growing number of
malignancies, including many genitourinary (GU) malignancies. These immune-based
therapies have demonstrated a distinct toxicity profile compared to traditional
chemotherapy and the targeted therapies directed at the vascular endothelial
growth factor pathway or the mammalian target of rapamycin pathway. Autoimmune
toxicity targeting the skin, gastrointestinal tract, or the endocrine organs are
some of the more common adverse events (AEs) noted with these therapies. Here in,
we report the results of a systematic review of the incidence of toxicities in GU
cancers reported in the phase II or phase III clinical trials using single-agent
PD-1 or PD-L1 inhibitors. Overall, the rate of serious (grades 3-4) AEs was noted
in approximately 15% of patients. The AEs noted were similar between all the
agents tested, highlighting the overall class effect of these therapies. The
incidence in GU cancers is similar to those seen in other malignancies. Given the
widespread and high volume real-world use of these agents, it is important for
oncologists to be familiar with these side effects to minimize the risks for
patients while undergoing therapy.
PMID- 28421162
TI - R-IDEAL: A Framework for Systematic Clinical Evaluation of Technical Innovations
in Radiation Oncology.
AB - The pace of innovation in radiation oncology is high and the window of
opportunity for evaluation narrow. Financial incentives, industry pressure, and
patients' demand for high-tech treatments have led to widespread implementation
of innovations before, or even without, robust evidence of improved outcomes has
been generated. The standard phase I-IV framework for drug evaluation is not the
most efficient and desirable framework for assessment of technological
innovations. In order to provide a standard assessment methodology for clinical
evaluation of innovations in radiotherapy, we adapted the surgical IDEAL
framework to fit the radiation oncology setting. Like surgery, clinical
evaluation of innovations in radiation oncology is complicated by continuous
technical development, team and operator dependence, and differences in quality
control. Contrary to surgery, radiotherapy innovations may be used in various
ways, e.g., at different tumor sites and with different aims, such as radiation
volume reduction and dose escalation. Also, the effect of radiation treatment can
be modeled, allowing better prediction of potential benefits and improved patient
selection. Key distinctive features of R-IDEAL include the important role of
predicate and modeling studies (Stage 0), randomization at an early stage in the
development of the technology, and long-term follow-up for late toxicity. We
implemented R-IDEAL for clinical evaluation of a recent innovation in radiation
oncology, the MRI-guided linear accelerator (MR-Linac). MR-Linac combines a
radiotherapy linear accelerator with a 1.5-T MRI, aiming for improved targeting,
dose escalation, and margin reduction, and is expected to increase the use of
hypofractionation, improve tumor control, leading to higher cure rates and less
toxicity. An international consortium, with participants from seven large cancer
institutes from Europe and North America, has adopted the R-IDEAL framework to
work toward coordinated, evidence-based introduction of the MR-Linac. R-IDEAL
holds the promise for timely, evidence-based introduction of radiotherapy
innovations with proven superior effectiveness, while preventing unnecessary
exposure of patients to potentially harmful interventions.
PMID- 28421163
TI - Phase I Trial of Triapine-Cisplatin-Paclitaxel Chemotherapy for Advanced Stage or
Metastatic Solid Tumor Cancers.
AB - Ribonucleotide reductase (RNR) is an enzyme involved in the de novo synthesis of
deoxyribonucleotides, which are critical for DNA replication and DNA repair.
Triapine is a small-molecule RNR inhibitor. A phase I trial studied the safety of
triapine in combination with cisplatin-paclitaxel in patients with advanced stage
or metastatic solid tumor cancers in an effort to capitalize on disrupted DNA
damage repair. A total of 13 patients with various previously treated cancers
were given a 96-h continuous intravenous (i.v.) infusion of triapine (40-120
mg/m2) on day 1, and then 3-h i.v. paclitaxel (80 mg/m2) followed by 1-h i.v.
cisplatin (50-75 mg/m2) on day 3. This combination regimen was repeated every 21
days. The maximum tolerated dose (MTD) for each agent was identified to be
triapine (80 mg/m2), cisplatin (50 mg/m2), and paclitaxel (80 mg/m2). Common
grade 3 or 4 toxicities included reversible anemia, leukopenia, thrombocytopenia,
or electrolyte abnormalities. The combination regimen of triapine-cisplatin
paclitaxel resulted in no objective responses; however, five (83%) of six
patients treated at the MTD had stable disease between 1 and 8 months duration.
This phase I study showed that the combination regimen of triapine-cisplatin
paclitaxel was safe and provides a rational basis for a follow-up phase II trial
to evaluate efficacy and progression-free survival in women with metastatic or
recurrent uterine cervix cancer.
PMID- 28421164
TI - "Targeted" Chemotherapy for Esophageal Cancer.
PMID- 28421165
TI - The Diverse Cellular and Animal Models to Decipher the Physiopathological Traits
of Mycobacterium abscessus Infection.
AB - Mycobacterium abscessus represents an important respiratory pathogen among the
rapidly-growing non-tuberculous mycobacteria. Infections caused by M. abscessus
are increasingly found in cystic fibrosis (CF) patients and are often refractory
to antibiotic therapy. The underlying immunopathological mechanisms of
pathogenesis remain largely unknown. A major reason for the poor advances in M.
abscessus research has been a lack of adequate models to study the acute and
chronic stages of the disease leading to delayed progress of evaluation of
therapeutic efficacy of potentially active antibiotics. However, the recent
development of cellular models led to new insights in the interplay between M.
abscessus with host macrophages as well as with amoebae, proposed to represent
the environmental host and reservoir for non-tuberculous mycobacteria. The
zebrafish embryo has also appeared as a useful alternative to more traditional
models as it recapitulates the vertebrate immune system and, due to its optical
transparency, allows a spatio-temporal visualization of the infection process in
a living animal. More sophisticated immunocompromised mice have also been
exploited recently to dissect the immune and inflammatory responses to M.
abscessus. Herein, we will discuss the limitations, advantages and potential
offered by these various models to study the pathophysiology of M. abscessus
infection and to assess the preclinical efficacy of compounds active against this
emerging human pathogen.
PMID- 28421166
TI - In vivo and In vitro Interactions between Pseudomonas aeruginosa and
Staphylococcus spp.
AB - The significance of polymicrobial infections is increasingly being recognized
especially in a biofilm context wherein multiple bacterial species-including both
potential pathogens and members of the commensal flora-communicate, cooperate,
and compete with each other. Two important bacterial pathogens that have
developed a complex network of evasion, counter-inhibition, and subjugation in
their battle for space and nutrients are Pseudomonas aeruginosa and
Staphylococcus aureus. Their strain- and environment-specific interactions, for
instance in the cystic fibrosis lung or in wound infections, show severe
competition that is generally linked to worse patient outcomes. For instance, the
extracellular factors secreted by P. aeruginosa have been shown to subjugate S.
aureus to persist as small colony variants (SCVs). On the other hand, data also
exist where S. aureus inhibits biofilm formation by P. aeruginosa but also
protects the pathogen by inhibiting its phagocytosis. Interestingly, such
interspecies interactions differ between the planktonic and biofilm phenotype,
with the extracellular matrix components of the latter likely being a key, and
largely underexplored, influence. This review attempts to understand the complex
relationship between P. aeruginosa and Staphylococcus spp., focusing on S.
aureus, that not only is interesting from the bacterial evolution point of view,
but also has important consequences for our understanding of the disease
pathogenesis for better patient management.
PMID- 28421167
TI - Iron and Virulence in Francisella tularensis.
AB - Francisella tularensis, the causative agent of tularemia, is a Gram-negative
bacterium that infects a variety of cell types including macrophages, and
propagates with great efficiency in the cytoplasm. Iron, essential for key
enzymatic and redox reactions, is among the nutrients required to support this
pathogenic lifestyle and the bacterium relies on specialized mechanisms to
acquire iron within the host environment. Two distinct pathways for iron
acquisition are encoded by the F. tularensis genome- a siderophore-dependent
ferric iron uptake system and a ferrous iron transport system. Genes of the Fur
regulated fslABCDEF operon direct the production and transport of the siderophore
rhizoferrin. Siderophore biosynthesis involves enzymes FslA and FslC, while
export across the inner membrane is mediated by FslB. Uptake of the rhizoferrin-
ferric iron complex is effected by the siderophore receptor FslE in the outer
membrane in a TonB-independent process, and FslD is responsible for uptake across
the inner membrane. Ferrous iron uptake relies largely on high affinity transport
by FupA in the outer membrane, while the Fur-regulated FeoB protein mediates
transport across the inner membrane. FslE and FupA are paralogous proteins,
sharing sequence similarity and possibly sharing structural features as well.
This review summarizes current knowledge of iron acquisition in this organism and
the critical role of these uptake systems in bacterial pathogenicity.
PMID- 28421168
TI - Contribution of the A. baumannii A1S_0114 Gene to the Interaction with Eukaryotic
Cells and Virulence.
AB - Genetic and functional studies showed that some components of the Acinetobacter
baumannii ATCC 17978 A1S_0112-A1S_0119 gene cluster are critical for biofilm
biogenesis and surface motility. Recently, our group has shown that the A1S_0114
gene was involved in biofilm formation, a process related with pathogenesis.
Confirming our previous results, microscopy images revealed that the ATCC 17978
Delta0114 derivative lacking this gene was unable to form a mature biofilm
structure. Therefore, other bacterial phenotypes were analyzed to determine the
role of this gene in the pathogenicity of A. baumannii ATCC 17978. The
interaction of the ATCC 17978 parental strain and the Delta0114 mutant with A549
human alveolar epithelial cells was quantified revealing that the A1S_0114 gene
was necessary for proper attachment to A549 cells. This dependency correlates
with the negative effect of the A1S_0114 deletion on the expression of genes
coding for surface proteins and pili-assembly systems, which are known to play a
role in adhesion. Three different experimental animal models, including
vertebrate and invertebrate hosts, confirmed the role of the A1S_0114 gene in
virulence. All of the experimental infection assays indicated that the virulence
of the ATCC 17978 was significantly reduced when this gene was inactivated.
Finally, we discovered that the A1S_0114 gene was involved in the production of a
small lipopeptide-like compound herein referred to as acinetin 505 (Ac-505). Ac
505 was isolated from ATCC 17978 spent media and its chemical structure was
interpreted by mass spectrometry. Overall, our observations provide novel
information on the role of the A1S_0114 gene in A. baumannii's pathobiology and
lay the foundation for future work to determine the mechanisms by which Ac-505,
or possibly an Ac-505 precursor, could execute critical functions as a secondary
metabolite.
PMID- 28421169
TI - High Prevalence of Virulence Genes in Specific Genotypes of Atypical
Enteropathogenic Escherichia coli.
AB - Atypical enteropathogenic Escherichia coli (aEPEC) strains are emerging
enteropathogens that have been detected worldwide. A collection of 228 aEPEC
strains (121 from diarrheal patients, 27 from healthy carriers, 47 from animals
and 33 from raw meats) were investigated for serotypes, virulence gene profiles
and phylogenetic relationships. Sixty-six O serogroups were identified. Serogroup
O51 was the most prevalent, followed by O119, O26 and O76. For the 20 virulence
genes detected, statistically significant differences were observed in the
overall prevalence of efa1 (lifA), nleB, nleE, set/ent, paa, and ehxA genes among
strains from diarrheal patients, healthy carriers, animals and raw meats,
respectively. Strains from diarrheal patients had significantly higher levels of
efa1 (lifA) (29.8 vs. 0%, P = 0.0002), nleB (41.3 vs. 7.4%, P = 0.0004), nleE
(43.8 vs. 7.4%, P = 0.0002) and set/ent (41.3 vs. 7.4%, P = 0.0004) genes than
strains obtained from healthy carriers. The paa gene was identified more often in
isolates from raw meats (63.6 vs. 14.8%, P < 0.0001), animals (42.6 vs. 14.8%, P
< 0.0122), and diarrheal patients (36.4 vs. 14.8%, P < 0.0225) than in strains
obtained from healthy carriers. The ehxA gene was detected more frequently in
strains from raw meats than in strains from diarrheal patients (27.3 vs. 2.5%, P
= 0.0000) and healthy carriers (27.3 vs. 7.4%, P = 0.0474). The phylogenetic
marker, yjaA, was more frequently observed in strains among healthy carriers than
in diarrheal patient strains. Among the 228 aEPEC strains, 79 sequence types
(STs) were identified. The prominent STs, which comprised strains carrying the
four OI-122 genes and lpfA, were ST40, ST328, and ST29. Overall, the results
indicate that aEPEC strains isolated in China are highly heterogeneous. aEPEC
strains that are potentially more pathogenic appear to be related to specific STs
or clonal complexes and serotypes. The high prevalence of diarrhea-associated
genes in animal or raw meat strains suggests a zoonotic transmission pathway for
potentially human pathogenic aEPEC.
PMID- 28421170
TI - Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Stress
Granule Formation Depending on Protein Kinase R-like Endoplasmic Reticulum Kinase
(PERK) in MARC-145 Cells.
AB - Stress granules (SGs) are sites of mRNA storage that are formed in response to
various conditions of stress, including viral infections. Porcine reproductive
and respiratory syndrome virus (PRRSV) is an Arterivirus that has been
devastating the swine industry worldwide since the late 1980s. In this study, we
found that infection of PRRSV strain WUH3 (genotype 2 PRRSV) induced stable
formation of robust SGs in MARC-145 cells, as demonstrated by the recruitment of
marker proteins of SGs, including TIA1, G3BP1, and eIF3eta. Treatment with
specific inhibitors or siRNAs against the stress kinases that are involved in SG
formation revealed that PRRSV induced SG formation through a PERK (protein kinase
R-like endoplasmic reticulum kinase)-dependent mechanism. Impairment of SG
assembly by concomitant knockdown of the SG marker proteins (TIA1, G3BP1, and
TIAR) did not affect PRRSV growth, while significantly enhanced PRRSV-induced NF
kappaB subunit p65 phosphorylation and inflammatory cytokine production. Taken
together, our results demonstrate that PRRSV induces SG formation via a PERK
dependent pathway and that SGs are involved in the signaling pathway of the PRRSV
induced inflammatory response in MARC-145 cells.
PMID- 28421171
TI - Tactile Stimulation to Stimulate Spontaneous Breathing during Stabilization of
Preterm Infants at Birth: A Retrospective Analysis.
AB - BACKGROUND AND AIMS: Tactile maneuvers to stimulate breathing in preterm infants
are recommended during the initial assessment at birth, but it is not known how
often and how this is applied. We evaluated the occurrence and patterns of
tactile stimulation during stabilization of preterm infants at birth. METHODS:
Recordings of physiological parameters and videos of infants <32 weeks
gestational age were retrospectively analyzed. Details of tactile stimulation
during the first 7 min after birth (timing, duration, type, and indication) were
noted. RESULTS: Stimulation was performed in 164/245 (67%) infants. The median
(IQR) GA was 28 6/7 (27 2/7-30 1/7) weeks, birth weight 1,153 (880-1,385) g,
Apgar score at 5 min was 8 (7-9), 140/245 (57%) infants were born after cesarean
section, and 134/245 (55%) were male. There were no significant differences
between the stimulated and the non-stimulated infants with regard to basic
characteristics. In the stimulated infants, the first episode of stimulation was
given at a median (IQR) of 114 (73-182) s after birth. Stimulation was repeated 3
(1-5) times, with a median (IQR) duration of 8 (4-16) s and a total duration of
32 (15-64) s. Modes of stimulation were: rubbing (68%) or flicking (2%) the soles
of the feet, rubbing the back (12%), a combination (9%), or other (8%). In 67% of
the stimulation episodes, a clear indication was noted (25% bradycardia, 57%
apnea, 48% hypoxemia, 43% combination) and an effect was observed in 18% of these
indicated stimulation episodes. A total effect of all stimulation episodes per
infant remains unclear, but infants who did not receive stimulation were more
often intubated in the delivery room (14/79 (18%) vs 12/164 (7%), p < 0.05).
CONCLUSION: There was a large variation in the use of tactile stimulation in
preterm infants during stabilization at birth. In most cases, there was an
indication for stimulation, but only in a small proportion an effect could be
observed.
PMID- 28421172
TI - Aspiration Risk and Respiratory Complications in Patients with Esophageal
Atresia.
AB - Chronic, long-term respiratory morbidity (CRM) is common in patients with a
history of repaired congenital esophageal atresia, typically associated with
tracheoesophageal fistula (EA/TEF). EA/TEF patients are at high risk of having
aspiration, and retrospective studies have associated CRM with both recurrent
aspiration and atopy. However, studies evaluating the association between CRM in
this population and either aspiration or atopy have reported conflicting results.
Furthermore, CRM in this population may be due to other related conditions as
well, such as tracheomalacia and/or recurrent infections. Aspiration is difficult
to confirm, short of lung biopsy. Moreover, even within the largest evidence base
assessing the association between CRM and aspiration, which has evaluated the
potential relationship between gastroesophageal reflux and asthma, findings are
contradictory. Studies attempting to relate CRM to prior aspiration events may
inadequately estimate the frequency and severity of previous aspiration episodes.
There is convincing evidence documenting that chronic, massive aspiration in
patients with repaired EA/TEF is associated with the development of
bronchiectasis. While chronic aspiration is likely associated with other CRM in
patients with repaired EA/TEF, this does not appear to have been confirmed by the
data currently available. Prospective studies that systematically evaluate
aspiration risk and allergic disease in patients with repaired EA/TEF and
document subsequent CRM will be needed to clarify the causes of CRM in this
population. Given the prevalence of CRM, patients with repaired EA/TEF should
ideally receive regular follow-up by multidisciplinary teams with expertise in
this condition, throughout both childhood and adulthood.
PMID- 28421173
TI - Cerebral Autoregulation, Brain Injury, and the Transitioning Premature Infant.
AB - Improvements in clinical management of the preterm infant have reduced the rates
of the two most common forms of brain injury, such as severe intraventricular
hemorrhage and white matter injury, both of which are contributory factors in the
development of cerebral palsy. Nonetheless, they remain a persistent challenge
and are associated with a significant increase in the risk of adverse
neurodevelopment outcomes. Repeated episodes of ischemia-reperfusion represent a
common pathway for both forms of injury, arising from discordance between
systemic blood flow and the innate regulation of cerebral blood flow in the
germinal matrix and periventricular white matter. Nevertheless, establishing firm
hemodynamic boundaries, as a part of neuroprotective strategy, has challenged
researchers. Existing measures either demonstrate inconsistent relationships with
injury, as in the case of mean arterial blood pressure, or are not feasible for
long-term monitoring, such as cardiac output estimated by echocardiography. These
challenges have led some researchers to focus on the mechanisms that control
blood flow to the brain, known as cerebrovascular autoregulation. Historically,
the function of the cerebrovascular autoregulatory system has been difficult to
quantify; however, the evolution of bedside monitoring devices, particularly near
infrared spectroscopy, has enabled new insights into these mechanisms and how
impairment of blood flow regulation may contribute to catastrophic injury. In
this review, we first seek to examine how technological advancement has changed
the assessment of cerebrovascular autoregulation in premature infants. Next, we
explore how clinical factors, including hypotension, vasoactive medications,
acute and chronic hypoxia, and ventilation, alter the hemodynamic state of the
preterm infant. Additionally, we examine how developmentally linked or acquired
dysfunction in cerebral autoregulation contributes to preterm brain injury. In
conclusion, we address exciting new approaches to the measurement of
autoregulation and discuss the feasibility of translation to the bedside.
PMID- 28421174
TI - Utility of Cardiovascular Magnetic Resonance-Derived Wave Intensity Analysis As a
Marker of Ventricular Function in Children with Heart Failure and Normal Ejection
Fraction.
AB - OBJECTIVE: This study sought to explore the diagnostic insight of cardiovascular
magnetic resonance (CMR)-derived wave intensity analysis to better study systolic
dysfunction in young patients with chronic diastolic dysfunction and preserved
ejection fraction (EF), comparing it against other echocardiographic and CMR
parameters. BACKGROUND: Evaluating systolic and diastolic dysfunctions in
children is challenging, and a gold standard method is currently lacking.
METHODS: Patients with presumed diastolic dysfunction [n = 18; nine aortic
stenosis (AS), five hypertrophic, and four restrictive cardiomyopathies] were
compared with age-matched control subjects (n = 18). All patients had no mitral
or aortic incompetence, significant AS, or reduced systolic EF. E/A ratio, E/E'
ratio, deceleration time, and isovolumetric contraction time were assessed on
echocardiography, and indexed left atrial volume (LAVi), acceleration time (AT),
ejection time (ET), and wave intensity analyses were calculated from CMR. The
latter was performed on CMR phase-contrast flow sequences, defining a ratio of
the peaks of the early systolic forward compression wave (FCW) and the end
systolic forward expansion wave (FEW). RESULTS: Significant differences between
patients and controls were seen in the E/E' ratio (8.7 +/- 4.0 vs. 5.1 +/- 1.3, p
= 0.001) and FCW/FEW ratio (2.5 +/- 1.6 vs. 7.2 +/- 4.2 * 10-5 m/s, p < 0.001),
as well as-as expected-LAVi (80.7 +/- 22.5 vs. 51.0 +/- 10.9 mL/m2, p < 0.001).
In particular, patients exhibited a lower FCW (2.5 +/- 1.6 vs. 7.2 +/- 4.2 * 10-5
m/s, p < 0.001) in the face of preserved EF (67 +/- 11 vs. 69 +/- 5%, p = 0.392),
as well as longer isovolumetric contraction time (49 +/- 7 vs. 34 +/- 7 ms, p <
0.001) and ET/AT (0.35 +/- 0.04 vs. 0.27 +/- 0.04, p < 0.001). CONCLUSION: This
study shows that the wave intensity-derived ratio summarizing systolic and
diastolic function could provide insight into ventricular function in children,
on top of CMR and echocardiography, and it was here able to identify an element
of ventricular dysfunction with preserved EF in a small group of young patients.
PMID- 28421176
TI - Distributed Learning: Revitalizing Anesthesiology Training in Resource-Limited
Ethiopia.
AB - BACKGROUND: Ethiopia has a significant paucity of available health-care workers.
Despite the increasing number of medical schools, there are not enough physician
instructors. Furthermore, availability and standardization of postgraduate
training are lacking. Modalities of e-learning have been shown to be successful
when used to impart medical education in other resource-limited countries. The
Emory University and Addis Ababa University (AAU) Departments of Anesthesiology
have formed a collaboration with the intent of improving the AAU Anesthesiology
residency program, one of two postgraduate training programs for anesthesiology
in Ethiopia. METHODS: An initial educational needs assessment identified areas in
the existing training program that required improvement. In this pilot study, we
describe how the current classroom-based curriculum is augmented by the
introduction of interactive educational sessions and distributed learning in the
form of video lectures. Video lectures covered topics based on areas identified
by Ethiopian residents and faculty. Interactive sessions included hands-on
ultrasound workshops and epidural placement practicums, a journal club, problem
based learning sessions, and a mock code simulation. Assessment of the additions
of the newly introduced blended learning technique was conducted via pre- and
posttests on the topics presented. RESULTS: Pre- to posttest score averages
increased from 54.5% to 83.6%. CONCLUSION: An expansion of educational resources
and modes of didactics are needed to fill the gaps that exist in Ethiopian
anesthesiology training. Incorporating distributed learning into the existing
didactic structure may lead to more efficacious instruction resulting in a higher
retention rate of information.
PMID- 28421175
TI - Factors Influencing Usability of a Smartphone App to Reduce Excessive Alcohol
Consumption: Think Aloud and Interview Studies.
AB - BACKGROUND: Interventions delivered by smartphone apps have the potential to help
drinkers reduce their consumption of alcohol. To optimize engagement and reduce
the high rates of attrition associated with the use of digital interventions, it
is necessary to ensure that an app's design and functionality is appropriate for
its intended purposes and target population. AIMS: To understand the usability of
an app to help people reduce their alcohol consumption. METHOD: The app, Drink
Less, contains a core module focusing on goal setting, supplemented by five
additional modules: self-monitoring and feedback, identity change, cognitive bias
re-training, action planning, and social comparison. Two studies were conducted,
a "think aloud" study performed with people using the app for the first time and
a semistructured interview study performed after users had had access to the app
for at least 2 weeks. A thematic analysis of the "think aloud" and interview
transcripts was conducted by one coder and verified by a second. RESULTS: Twenty
four participants, half of whom were women and half from disadvantaged groups,
took part in the two studies. Three main themes identified in the data were
"Feeling lost and unsure of what to do next," "Make the app easy to use," and
"Make the app beneficial and rewarding to use." These themes reflected
participants' need for (i) guidance, particularly when first using the app or
when entering data; (ii) the data entry process to be simple and the navigation
intuitive; (iii) neither the amount of text nor range of options to be
overwhelming; (iv) the app to reward them for effort and progress; and (v) it to
be clear how the app could help alcohol reduction goals be reached. CONCLUSION:
First-time and experienced users want an alcohol reduction app to be easy,
rewarding, and beneficial to use. An easy-to-use app would reduce user burden,
offer ongoing help, and be esthetically pleasing. A rewarding and beneficial app
would provide positive reinforcement, give feedback about progress, and
demonstrate credibility. Users need help when first using the app, and they need
a compelling reason to continue using it.
PMID- 28421177
TI - Variation in Population Vulnerability to Heat Wave in Western Australia.
AB - Heat waves (HWs) have killed more people in Australia than all other natural
hazards combined. Climate change is expected to increase the frequency, duration,
and intensity of HWs and leads to a doubling of heat-related deaths over the next
40 years. Despite being a significant public health issue, HWs do not attract the
same level of attention from researchers, policy makers, and emergency management
agencies compared to other natural hazards. The purpose of the study was to
identify risk factors that might lead to population vulnerability to HW in
Western Australia (WA). HW vulnerability and resilience among the population of
the state of WA were investigated by using time series analysis. The health
impacts of HWs were assessed by comparing the associations between hospital
emergency department (ED) presentations, hospital admissions and mortality data,
and intensities of HW. Risk factors including age, gender, socioeconomic status
(SES), remoteness, and geographical locations were examined to determine whether
certain population groups were more at risk of adverse health impacts due to
extreme heat. We found that hospital admissions due to heat-related conditions
and kidney diseases, and overall ED attendances, were sensitive indicators of HW.
Children aged 14 years or less and those aged 60 years or over were identified as
the most vulnerable populations to HWs as shown in ED attendance data. Females
had more ED attendances and hospital admissions due to kidney diseases; while
males had more heat-related hospital admissions than females. There were
significant dose-response relationships between HW intensity and SES, remoteness,
and health service usage. The more disadvantaged and remotely located the
population, the higher the health service usage during HWs. Our study also found
that some population groups and locations were resilient to extreme heat. We
produced a mapping tool, which indicated geographic areas throughout WA with
various vulnerability and resilience levels to HW. The findings from this study
will allow local government, community service organizations, and agencies in
health, housing, and education to better identify and understand the degree of
vulnerability to HW throughout the state, better target preparatory strategies,
and allocate limited resources to those most in need.
PMID- 28421179
TI - Synergy-Based Bilateral Port: A Universal Control Module for Tele-Manipulation
Frameworks Using Asymmetric Master-Slave Systems.
AB - Endowing tele-manipulation frameworks with the capability to accommodate a
variety of robotic hands is key to achieving high performances through permitting
to flexibly interchange the end-effector according to the task considered. This
requires the development of control policies that not only cope with asymmetric
master-slave systems but also whose high-level components are designed in a
unified space in abstraction from the devices specifics. To address this dual
challenge, a novel synergy port is developed that resolves the kinematic,
sensing, and actuation asymmetries of the considered system through generating
motion and force feedback references in the hardware-independent hand postural
synergy space. It builds upon the concept of the Cartesian-based synergy matrix,
which is introduced as a tool mapping the fingertips Cartesian space to the
directions oriented along the grasp principal components. To assess the
effectiveness of the proposed approach, the synergy port has been integrated into
the control system of a highly asymmetric tele-manipulation framework, in which
the 3-finger hand exoskeleton HEXOTRAC is used as a master device to control the
SoftHand, a robotic hand whose transmission system relies on a single motor to
drive all joints along a soft synergistic path. The platform is further enriched
with the vision-based motion capture system Optitrack to monitor the 6D
trajectory of the user's wrist, which is used to control the robotic arm on which
the SoftHand is mounted. Experiments have been conducted with the humanoid robot
COMAN and the KUKA LWR robotic manipulator. Results indicate that this bilateral
interface is highly intuitive and allows users with no prior experience to reach,
grasp, and transport a variety of objects exhibiting very different shapes and
impedances. In addition, the hardware and control solutions proved capable of
accommodating users with different hand kinematics. Finally, the proposed control
framework offers a universal, flexible, and intuitive interface allowing for the
performance of effective tele-manipulations.
PMID- 28421180
TI - Usability Evaluations of a Wearable Inertial Sensing System and Quality of
Movement Metrics for Stroke Survivors by Care Professionals.
AB - BACKGROUND: Inertial motion capture systems are used in many applications such as
measuring the movement quality in stroke survivors. The absence of clinical
effectiveness and usability evidence in these assistive technologies into
rehabilitation has delayed the transition of research into clinical practice.
Recently, a new inertial motion capture system was developed in a project, called
INTERACTION, to objectively measure the quality of movement (QoM) in stroke
survivors during daily-life activity. With INTERACTION, we are to be able to
investigate into what happens with patients after discharge from the hospital.
Resulting QoM metrics, where a metric is defined as a measure of some property,
are subsequently presented to care professionals. Metrics include for example:
reaching distance, walking speed, and hand distribution plots. The latter shows a
density plot of the hand position in the transversal plane. The objective of this
study is to investigate the opinions of care professionals in using these metrics
obtained from INTERACTION and its usability. METHODS: By means of a semi
structured interview, guided by a presentation, presenting two patient reports.
Each report includes several QoM metric (like reaching distance, hand position
density plots, shoulder abduction) results obtained during daily-life
measurements and in clinic and were evaluated by care professionals not related
to the project. The results were compared with care professionals involved within
the INTERACTION project. Furthermore, two questionnaires (5-point Likert and open
questionnaire) were handed over to rate the usability of the metrics and to
investigate if they would like such a system in their clinic. RESULTS: Eleven
interviews were conducted, where each interview included either two or three care
professionals as a group, in Switzerland and The Netherlands. Evaluation of the
case reports (CRs) by participants and INTERACTION members showed a high
correlation for both lower and upper extremity metrics. Participants were most in
favor of hand distribution plots during daily-life activities. All participants
mentioned that visualizing QoM of stroke survivors over time during daily-life
activities has more possibilities compared to current clinical assessments. They
also mentioned that these metrics could be important for self-evaluation of
stroke survivors. DISCUSSION: The results showed that most participants were able
to understand the metrics presented in the CRs. For a few metrics, it remained
difficult to assess the underlying cause of the QoM. Hence, a combination of
metrics is needed to get a better insight of the patient. Furthermore, it remains
important to report the state (e.g., how the patient feels), its surroundings
(outside, inside the house, on a slippery surface), and detail of specific
activities (does the patient grasps a piece of paper or a heavy cooking pan but
also dual tasks). Altogether, it remains a questions how to determine what the
patient is doing and where the patient is doing his or her activities.
PMID- 28421178
TI - Applying Precision Public Health to Prevent Preterm Birth.
AB - Preterm birth (PTB) is one of the major health-care challenges of our time. Being
born too early is associated with major risks to the child with potential for
serious consequences in terms of life-long disability and health-care costs.
Discovering how to prevent PTB needs to be one of our greatest priorities. Recent
advances have provided hope that a percentage of cases known to be related to
risk factors may be amenable to prevention; but the majority of cases remain of
unknown cause, and there is little chance of prevention. Applying the principle
of precision public health may offer opportunities previously unavailable.
Presented in this article are ideas that may improve our abilities in the fields
of studying the effects of migration and of populations in transition, public
health programs, tobacco control, routine measurement of length of the cervix in
mid-pregnancy by ultrasound imaging, prevention of non-medically indicated late
PTB, identification of pregnant women for whom treatment of vaginal infection may
be of benefit, and screening by genetics and other "omics." Opening new research
in these fields, and viewing these clinical problems through a prism of precision
public health, may produce benefits that will affect the lives of large numbers
of people.
PMID- 28421181
TI - MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive
Breast Cancer.
AB - Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of
monocarboxylates such as lactate and pyruvate and a marker of mitochondrial
metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for
catabolite uptake from the tumor microenvironment to support mitochondrial
metabolism. We studied the protein expression of MCT1 in a broad group of breast
invasive ductal carcinoma specimens to determine its association with breast
cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by
immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor
bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen
receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were
human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were
triple negative breast cancers (TNBC). MCT1 expression was quantified by digital
pathology with Aperio software. The intensity of the staining was measured on a
continuous scale (0-black to 255-bright white) using a co-localization algorithm.
Statistical analysis was performed using a linear mixed model. Results: High MCT1
expression was more commonly found in TNBC compared to ER+ and/or PR+ and
compared to HER-2+ (p < 0.001). Tumors with an in-situ component were less likely
to stain strongly for MCT1 (p < 0.05). High nuclear grade was associated with
higher MCT1 staining (p < 0.01). Higher T stage tumors were noted to have a
higher expression of MCT1 (p < 0.05). High MCT1 staining in cancer cells was
associated with shorter progression free survival, increased risk of recurrence,
and larger size independent of TNBC status (p < 0.05). Conclusion: MCT1
expression, which is a marker of high catabolite uptake and mitochondrial
metabolism, is associated with recurrence in breast invasive ductal carcinoma.
MCT1 expression as quantified with digital image analysis may be useful as a
prognostic biomarker and to design clinical trials using MCT1 inhibitors.
PMID- 28421182
TI - TGF-beta1 Pretreatment Improves the Function of Mesenchymal Stem Cells in the
Wound Bed.
AB - The wound healing process initiates after injury to a tissue and involves a
series of orchestrated events to minimize the invasion of foreign matters such as
bacteria and efficiently regenerate the damaged tissue. A variety of cells must
be recruited to the tissue during wound healing. However, this process is
severely disrupted in patients suffering from chronic illness, including
diabetes, leading to impaired healing or non-healing wounds. Current avenues of
treatment include negative-pressure therapy, wound debridement, growth factor
replacement, and cell-based therapies. Among these therapies, mesenchymal stem
cells (MSCs) delivery to the wound holds a very high promise due to the innate
abilities of MSCs that include immunogenicity, plasticity, and self-renewal. Bone
marrow derived MSCs have been shown to promote more rapid wound healing by
increased cytokine production in diabetic mice. However, the lack of
understanding of the mechanical and chemical interaction of the transplanted MSCs
with the factors present in the regenerative niches limits their efficacy in the
wound bed. In this study, we sought to understand how the changes in MSC
biochemical and biophysical properties can affect their function in vitro and in
vivo. We demonstrate that pretreatment of MSCs with the mechano-stimulatory
soluble factor transforming growth factor (TGF-beta1), which is highly expressed
in injury sites, improves wound closure in a syngeneic murine wound model. This
improved wound closure correlated with increased invasion into the wound bed. In
vitro studies demonstrated that TGF-beta1 pretreatment expedited wound closure by
increasing adhesion, traction force, and migration even after removal of the
stimulus. Furthermore, this response was mediated by the cytoskeletal protein
focal adhesion kinase. Taken together, this study suggests that defined chemical
stimuli can benefit site specific adaptability of MSCs to improve their function
and therapeutic usefulness.
PMID- 28421184
TI - The Proteasomal ATPases Use a Slow but Highly Processive Strategy to Unfold
Proteins.
AB - All domains of life have ATP-dependent compartmentalized proteases that sequester
their peptidase sites on their interior. ATPase complexes will often associate
with these compartmentalized proteases in order to unfold and inject substrates
into the protease for degradation. Significant effort has been put into
understanding how ATP hydrolysis is used to apply force to proteins and cause
them to unfold. The unfolding kinetics of the bacterial ATPase, ClpX, have been
shown to resemble a fast motor that traps unfolded intermediates as a strategy to
unfold proteins. In the present study, we sought to determine if the proteasomal
ATPases from eukaryotes and archaea exhibit similar unfolding kinetics. We found
that the proteasomal ATPases appear to use a different kinetic strategy for
protein unfolding, behaving as a slower but more processive and efficient
translocation motor, particularly when encountering a folded domain. We expect
that these dissimilarities are due to differences in the ATP binding/exchange
cycle, the presence of a trans-arginine finger, or the presence of a threading
ring (i.e., the OB domain), which may be used as a rigid platform to pull folded
domains against. We speculate that these differences may have evolved due to the
differing client pools these machines are expected to encounter.
PMID- 28421183
TI - Organ-to-Organ Communication: A Drosophila Gastrointestinal Tract Perspective.
AB - The long-term maintenance of an organism's homeostasis and health relies on the
accurate regulation of organ-organ communication. Recently, there has been
growing interest in using the Drosophila gastrointestinal tract to elucidate the
regulatory programs that underlie the complex interactions between organs. Data
obtained in this field have dramatically improved our understanding of how organ
organ communication contributes to the regulation of various aspects of the
intestine, including its metabolic and physiological status. However, although
research uncovering regulatory programs associated with interorgan communication
has provided key insights, the underlying mechanisms have not been extensively
explored. In this review, we highlight recent findings describing gut-neighbor
and neighbor-neighbor communication models in adults and larvae, respectively,
with a special focus on how a range of critical strategies concerning continuous
interorgan communication and adjustment can be used to manipulate different
aspects of biological processes. Given the high degree of similarity between the
Drosophila and mammalian intestinal epithelia, it can be anticipated that further
analyses of the Drosophila gastrointestinal tract will facilitate the discovery
of similar mechanisms underlying organ-organ communication in other mammalian
organs, such as the human intestine.
PMID- 28421185
TI - Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota
Transplantation for Recurrent Clostridium difficile Infection in a Pediatric
Heart Transplant Patient.
AB - The microbiome is increasingly recognized as an important influence on human
health and many of the comorbidities that affect patients after solid organ
transplantation (SOT) have been shown to involve changes in gut bacterial
populations. Thus, microbiome changes in an individual patient may have important
health implications after SOT but this area remains understudied. We describe
changes in the composition of the fecal microbiome from a pediatric heart
transplant recipient before and >2.5 years after he underwent repeated fecal
microbiota transplantation (FMT) for recurrent Clostridium difficile infection
(CDI). With both documented episodes of CDI, there was marked loss of bacterial
diversity with overgrowth of Proteobacteria (>98.9% of phyla identified)
associated with symptomatic colitis that was corrected after FMT. We hypothesize
that a second CDI occurring after FMT was related to incomplete restoration of
normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes
and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae. Following
the second FMT, there was a gradual shift in gut bacterial composition coincident
with the recipient developing lymphonodular hyperplasia of the colon and painless
hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF).
This case documents dynamic changes in the bacterial microbiome after FMT and
suggests that MMF may influence the gut microbiome with consequences for the
patient.
PMID- 28421186
TI - Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and
Canine Mass Vaccination against Rabies in N'Djamena, Chad.
AB - Rabies claims approximately 59,000 human lives annually and is a potential risk
to 3.3 billion people in over 100 countries worldwide. Despite being fatal in
almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most
common vector, and the timely administration of post-exposure prophylaxis (PEP)
to exposed victims. For the control and prevention of human rabies in N'Djamena,
the capital city of Chad, a free mass vaccination campaign for dogs was organized
in 2012 and 2013. The campaigns were monitored by parallel studies on the
incidence of canine rabies based on diagnostic testing of suspect animals and the
incidence of human bite exposure recorded at selected health facilities. Based on
the cost description of the campaign and the need for PEP registered in health
centers, three cost scenarios were compared: cumulative cost-efficiency of (1)
PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and
maximal communication between human health and veterinary workers (One Health
communication). Assuming ideal One Health communication, the cumulative
prospective cost of dog vaccination and PEP break even with the cumulative
prospective cost of PEP alone in the 10th year from the start of the calculation
(2012). The cost efficiency expressed in cost per human exposure averted is much
higher with canine vaccination and One Health communication than with PEP alone.
As shown in other studies, our cost-effectiveness analysis highlights that canine
vaccination is financially the best option for animal rabies control and rabies
prevention in humans. This study also provides evidence of the beneficial effect
of One Health communication. Only with close communication between the human and
animal health sectors will the decrease in animal rabies incidence be translated
into a decline for PEP. An efficiently applied One Health concept would largely
reduce the cost of PEP in resource poor countries and should be implemented for
zoonosis control in general.
PMID- 28421187
TI - Subset-Specific Expression of Toll-Like Receptors by Bovine Afferent Lymph
Dendritic Cells.
AB - Within the ruminant system, several possibilities exist to generate dendritic
cells migrating out from the tissue into the regional draining lymph nodes as
afferent lymph dendritic cells (ALDCs). Here, we analyzed toll-like receptor
(TLR) 1-10 mRNA expression by using quantitative real-time PCR in highly purified
subsets of bovine ALDC. As TLR expression may be influenced by pathogens or
vaccines and their adjuvant, it is necessary to understand what TLRs are
expressed in a steady-state system to elucidate specific differences and to
potentially optimize targeted vaccines. In this study, we have assessed the TLR
expression profiles of the four main bovine ALDC subsets [cDC1 and cDC2 (subsets
2-4)]. We demonstrate differences in TLR expression between the four subsets that
may reflect the ability of these cells to respond to different pathogens or to
respond to adjuvants.
PMID- 28421188
TI - Pulmonary arteriovenous malformations: evidence of physician under-education.
AB - PAVMs pose unique management challenges; publication patterns indicate their
importance remains poorly recognised http://ow.ly/7iIT304WYl2.
PMID- 28421189
TI - Optic Nerve Sheath Diameter Ultrasound Evaluation in Intensive Care Unit:
Possible Role and Clinical Aspects in Neurological Critical Patients' Daily
Monitoring.
AB - Background. The increase of the optic nerve sheath diameter (ONSD) is a reliable,
noninvasive sonographic marker of intracranial hypertension. Aim of the study was
to demonstrate the efficacy of ONSD evaluation, when monitoring neurocritical
patients, to early identify malignant intracranial hypertension in patients with
brain death (BD). Methods. Data from ultrasound ONSD evaluation have been
retrospectively analyzed in 21 sedated critical patients with neurological
diseases who, during their clinical course, developed BD. 31 nonneurological
controls were used for standard ONSD reference. Results. Patients with
neurological diseases, before BD, showed higher ONSD values than control group
(CTRL: RT 0.45 +/- 0.03 cm; LT 0.45 +/- 0.02 cm; pre-BD: RT 0.54 +/- 0.02 cm; LT
0.55 +/- 0.02 cm; p < 0.000) even without intracranial hypertension, evaluated
with invasive monitoring. ONSD was further significantly markedly increased in
respect to the pre-BD evaluation in neurocritical patients after BD, with mean
values above 0.7 cm (RT 0.7 +/- 0.02 cm; LT 0.71 +/- 0.02 cm; p < 0.000), with a
corresponding dramatic raise in intracranial pressure. Logistic regression
analysis showed a strong correlation between ONSD and ICP (R 0,895, p < 0.001).
Conclusions. ONSD is a reliable marker of intracranial hypertension, easy to be
performed with a minimal training. Routine ONSD daily monitoring could be of help
in Intensive Care Units when invasive intracranial pressure monitoring is not
available, to early recognize intracranial hypertension and to suspect BD in
neurocritical patients.
PMID- 28421190
TI - First-Trimester Crown-Rump Length and Embryonic Volume of Fetuses with Structural
Congenital Abnormalities Measured in Virtual Reality: An Observational Study.
AB - Background. With the introduction of three-dimensional (3D) ultrasound it has
become possible to measure volumes. The relative increase in embryonic volume
(EV) is much larger than that of the crown-rump length (CRL) over the same time
period. We examined whether EV is a better parameter to determine growth
restriction in fetuses with structural congenital abnormalities. Study Design,
Subjects, and Outcome Measures. CRL and EV were measured using a Virtual Reality
(VR) system in prospectively collected 3D ultrasound volumes of 56 fetuses
diagnosed with structural congenital abnormalities in the first trimester of
pregnancy (gestational age 7+5 to 14+5 weeks). Measured CRL and EV were converted
to z-scores and to percentages of the expected mean using previously published
reference curves of euploid fetuses. The one-sample t-test was performed to test
significance. Results. The EV was smaller than expected for GA in fetuses with
structural congenital abnormalities (-35% p < 0.001, z-score -1.44 p < 0.001),
whereas CRL was not (-6.43% p = 0.118, z-score -0.43 p = 0.605). Conclusions.
CRL is a less reliable parameter to determine growth restriction in fetuses with
structural congenital abnormalities as compared with EV. By measuring EV, growth
restriction in first-trimester fetuses with structural congenital abnormalities
becomes more evident and enables an earlier detection of these cases.
PMID- 28421191
TI - Prospective Multicentre Study on the Epidemiology and Current Therapeutic
Management of Severe Bronchiolitis in Spain.
AB - Objective. To determine the epidemiology and therapeutic management of patients
with severe acute bronchiolitis (AB) admitted to paediatric intensive care units
(PICUs) in Spain. Design. Descriptive, prospective, multicentre study. Setting.
Sixteen Spanish PICUs. Patients. Patients with severe AB who required admission
to any of the participating PICUs over 1 year. Interventions. Both
epidemiological variables and medical treatment received were recorded. Results.
A total of 262 patients were recruited; 143 were male (54.6%), with median age of
1 month (0-23). Median stay in the PICU was 7 days (1-46). Sixty patients (23%)
received no nebuliser treatment, while the rest received a combination of
inhalation therapies. One-quarter of patients (24.8%) received corticosteroids
and 56.5% antibiotic therapy. High-flow oxygen therapy was used in 14.3% and
noninvasive ventilation (NIV) was used in 75.6%. Endotracheal intubation was
required in 24.4% of patients. Younger age, antibiotic therapy, and invasive
mechanical ventilation (IMV) were risk factors that significantly increased the
stay in the PICU. Conclusions. Spanish PICUs continue to routinely use nebulised
bronchodilator treatment and corticosteroid therapy. Despite NIV being widely
used in this condition, intubation was required in one-quarter of cases. Younger
age, antibiotic therapy, and IMV were associated with a longer stay in the PICU.
PMID- 28421192
TI - Exercise and Protein Intake: A Synergistic Approach against Sarcopenia.
AB - Sarcopenia, the age-dependent loss of muscle mass and function/strength, is
increasingly recognized as a major risk factor for adverse outcomes in frail
older people. As such, the skeletal muscle is a relevant target for interventions
aimed at preventing or postponing the occurrence of negative health-related
events in late life. The association among physical inactivity, insufficient
intake of energy and protein, and poor muscle health in older adults suggests
that physical exercise and targeted nutritional supplementation may offer
substantial therapeutic gain against sarcopenia and its negative correlates. This
view is supported by observational studies as well as by small-scale clinical
trials. In this review, we summarize the available evidence on the beneficial
effects of behavioral interventions on sarcopenia. We also briefly describe how
the knowledge gathered so far has been used to design the "Sarcopenia and
Physical fRailty IN older people: multicomponenT Treatment strategies" (SPRINTT)
project. The randomized clinical trial conducted within SPRINTT will provide
robust evidence on the effectiveness of exercise and nutrition at preventing
negative outcomes associated with sarcopenia and physical frailty.
PMID- 28421194
TI - Dihydromyricetin Protects against Diabetic Cardiomyopathy in Streptozotocin
Induced Diabetic Mice.
AB - Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic
patients. The present study sought to explore the potential effects of
dihydromyricetin (DHM) on DCM and its possible mechanism. A diabetic model was
induced by intraperitoneal injection of streptozotocin (STZ) in C57BL/6J mice.
Two weeks after the STZ injection, mice were randomly allocated into the
following 4 groups for treatment: the control group (CON), the control treated
with DHM group (CON + DHM), the diabetes group (DM), and the diabetes treated
with DHM group (DM + DHM). DHM was dissolved in distilled water and administered
daily by gavage. For 14 weeks, the CON + DHM group and DM + DHM group were given
a dose of 100 mg/kg/day DHM (Sigma-Aldrich), while the CON and DM groups were
intragastrically given equivalent volumes of distilled water. Assessments and
comparisons were made among the groups based on cardiac function and structural
changes, inflammation factors, markers of oxidative stress, mitochondria
function, apoptosis, and autophagy. The DHM treatment normalized body weight,
preserved cardiac function, attenuated oxidative stress (MDA, SOD, and GSH-Px),
reduced the levels of inflammation factors (IL-6, TNF-alpha), alleviated
pathological changes, improved mitochondrial function (ATP content, CS activity,
and complex Iota/IotaIota/IotaIotaIota/IotaV/V activities), inhibited cardiac
apoptosis, and restored autophagy in diabetic mice. DHM may have a great
therapeutic potential in the treatment of DCM.
PMID- 28421193
TI - Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease.
AB - Prevention of bone fractures is one goal of therapy for patients with chronic
kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney
Disease: Improving Global Outcomes guidelines. CKD patients, including those on
hemodialysis, are at higher risk for fractures and fracture-related death
compared to people with normal kidney function. However, few clinicians focus on
this issue as it is very difficult to estimate bone fragility. Additionally,
uremia-related bone fragility has a more complicated pathological process
compared to osteoporosis. There are many uremia-associated factors that
contribute to bone fragility, including severe secondary hyperparathyroidism,
skeletal resistance to parathyroid hormone, and bone mineralization disorders.
Uremia also aggravates bone volume loss, disarranges microarchitecture, and
increases the deterioration of material properties of bone through abnormal bone
cells or excess oxidative stress. In this review, we outline the prevalence of
fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and
discuss possible factors that exacerbate the mechanical properties of bone.
PMID- 28421195
TI - Role of Demyelination Efficiency within Acellular Nerve Scaffolds during Nerve
Regeneration across Peripheral Defects.
AB - Hudson's optimized chemical processing method is the most commonly used chemical
method to prepare acellular nerve scaffolds for the reconstruction of large
peripheral nerve defects. However, residual myelin attached to the basal laminar
tube has been observed in acellular nerve scaffolds prepared using Hudson's
method. Here, we describe a novel method of producing acellular nerve scaffolds
that eliminates residual myelin more effectively than Hudson's method through the
use of various detergent combinations of sulfobetaine-10, sulfobetaine-16, Triton
X-200, sodium deoxycholate, and peracetic acid. In addition, the efficacy of this
new scaffold in repairing a 1.5 cm defect in the sciatic nerve of rats was
examined. The modified method produced a higher degree of demyelination than
Hudson's method, resulting in a minor host immune response in vivo and providing
an improved environment for nerve regeneration and, consequently, better
functional recovery. A morphological study showed that the number of regenerated
axons in the modified group and Hudson group did not differ. However, the
autograft and modified groups were more similar in myelin sheath regeneration
than the autograft and Hudson groups. These results suggest that the modified
method for producing a demyelinated acellular scaffold may aid functional
recovery in general after nerve defects.
PMID- 28421196
TI - Synthesis of L-Ascorbyl Flurbiprofenate by Lipase-Catalyzed Esterification and
Transesterification Reactions.
AB - The synthesis of L-ascorbyl flurbiprofenate was achieved by esterification and
transesterification in nonaqueous organic medium with Novozym 435 lipase as
biocatalyst. The conversion was greatly influenced by the kinds of organic
solvents, speed of agitation, catalyst loading amount, reaction time, and molar
ratio of acyl donor to L-ascorbic acid. A series of solvents were investigated,
and tert-butanol was found to be the most suitable from the standpoint of the
substrate solubility and the conversion for both the esterification and
transesterification. When flurbiprofen was used as acyl donor, 61.0% of L
ascorbic acid was converted against 46.4% in the presence of flurbiprofen methyl
ester. The optimal conversion of L-ascorbic acid was obtained when the initial
molar ratio of acyl donor to ascorbic acid was 5 : 1. kinetics parameters were
solved by Lineweaver-Burk equation under nonsubstrate inhibition condition. Since
transesterification has lower conversion, from the standpoint of productivity and
the amount of steps required, esterification is a better method compared to
transesterification.
PMID- 28421197
TI - Ginsenoside Rg1 Ameliorates Cigarette Smoke-Induced Airway Fibrosis by
Suppressing the TGF-beta1/Smad Pathway In Vivo and In Vitro.
AB - Small airway fibrosis is a key pathological process accompanying chronic
obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast
transdifferentiation and excessive extracellular matrix deposition. Ginsenoside
Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert
an antifibrotic effect in many tissues. However, little is known about the
underlying mechanism and whether ginsenoside Rg1 can exert an effect on small
airway fibrosis. We investigated the anti-small airway fibrosis effects of
ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats. We found
that ginsenoside Rg1 effectively reduced the degree of pulmonary fibrosis,
decreased the expression of alpha-smooth muscle actin, collagen I, and matrix
metalloproteinase 9, and maintained the ratio of matrix metalloproteinase 9 to
tissue inhibitor of metalloproteinase 1. Importantly, ginsenoside Rg1
significantly attenuated cigarette smoke extract-induced upregulation of
transforming growth factor beta1, TGF-beta receptor I, phospho-Smad2, and phospho
Smad3. In addition, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-beta
receptor I-Smad2/3 inhibitor. Collectively, these results suggest that
ginsenoside Rg1 may suppress cigarette smoke-induced airway fibrosis in pulmonary
fibroblasts and COPD rats by inhibiting the TGF-beta1/Smad signaling pathway.
PMID- 28421198
TI - Identify High-Quality Protein Structural Models by Enhanced K-Means.
AB - Background. One critical issue in protein three-dimensional structure prediction
using either ab initio or comparative modeling involves identification of high
quality protein structural models from generated decoys. Currently, clustering
algorithms are widely used to identify near-native models; however, their
performance is dependent upon different conformational decoys, and, for some
algorithms, the accuracy declines when the decoy population increases. Results.
Here, we proposed two enhanced K-means clustering algorithms capable of robustly
identifying high-quality protein structural models. The first one employs the
clustering algorithm SPICKER to determine the initial centroids for basic K-means
clustering (SK-means), whereas the other employs squared distance to optimize the
initial centroids (K-means++). Our results showed that SK-means and K-means++
were more robust as compared with SPICKER alone, detecting 33 (59%) and 42 (75%)
of 56 targets, respectively, with template modeling scores better than or equal
to those of SPICKER. Conclusions. We observed that the classic K-means algorithm
showed a similar performance to that of SPICKER, which is a widely used algorithm
for protein-structure identification. Both SK-means and K-means++ demonstrated
substantial improvements relative to results from SPICKER and classical K-means.
PMID- 28421200
TI - Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before
and after Exercise.
AB - Purpose. The aim of the present study was to elucidate the metabolic mechanisms
associated with chronic fatigue syndrome (CFS) via an analysis of urine
metabolites prior to and following exercise in a rat model. Methods. A rat model
of CFS was established using restraint-stress, forced exercise, and crowded and
noisy environments over a period of 4 weeks. Behavioral experiments were
conducted in order to evaluate the model. Urine metabolites were analyzed via gas
chromatography-mass spectrometry (GC-MS) in combination with multivariate
statistical analysis before and after exercise. Results. A total of 20
metabolites were detected in CFS rats before and after exercise. Three metabolic
pathways (TCA cycle; alanine, aspartate, and glutamate metabolism; steroid
hormone biosynthesis) were significantly impacted before and after exercise,
while sphingolipid metabolism alone exhibited significant alterations after
exercise only. Conclusion. In addition to metabolic disturbances involving some
energy substances, alterations in steroid hormone biosynthesis and sphingolipid
metabolism were detected in CFS rats. Sphingosine and 21-hydroxypregnenolone may
be key biomarkers of CFS, potentially offering evidence in support of immune
dysfunction and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity in
patients with CFS.
PMID- 28421199
TI - Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity:
Involvement of GSK3beta Phosphorylation by Akt and ERK through the Mitochondrial
Intrinsic Apoptotic Pathway.
AB - Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has
recently shown neuroprotective effects in several neurological diseases,
particularly in Parkinson's disease (PD). The goal of the present study was to
confirm VPA's dose-dependent neuroprotective propensities in the MPP+ model of PD
in primary dopamine (DA) neurons and to investigate the underlying molecular
mechanisms using specific mitogen-activated protein kinases (MAPKs) and
phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors. VPA reversed
MPP+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular
signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase
kinase 3beta (GSK3beta) activation through induction of GSK3beta phosphorylation.
Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3beta
phosphorylation and diminished the VPA-induced neuroprotective effect. These
findings indicated that VPA's neuroprotective effect in the MPP+-model of PD is
associated with GSK3beta phosphorylation via Akt and ERK activation in the
mitochondrial intrinsic apoptotic pathway. Thus, VPA may be a promising
therapeutic candidate for clinical treatment of PD.
PMID- 28421201
TI - Reconstructive and Regenerative Therapy of Atrophic Jaws with New Implant
Techniques: Preclinical and Clinical Studies.
PMID- 28421203
TI - Novel Computational Approaches and Applications in Cancer Research.
PMID- 28421202
TI - The Interaction between HIV and Intestinal Helminth Parasites Coinfection with
Nutrition among Adults in KwaZulu-Natal, South Africa.
AB - In South Africa few studies have examined the effects of the overlap of HIV and
helminth infections on nutritional status. This cross-sectional study
investigated the interaction between HIV and intestinal helminths coinfection
with nutritional status among KwaZulu-Natal adults. Participants were recruited
from a comprehensive primary health care clinic and stratified based on their
HIV, stool parasitology, IgE, and IgG4 results into four groups: the uninfected,
HIV infected, helminth infected, and HIV-helminth coinfected groups. The
nutritional status was assessed using body mass index, 24-hour food recall, micro
, and macronutrient biochemical markers. Univariate and multivariate multinomial
probit regression models were used to assess nutritional factors associated with
singly and dually infected groups using the uninfected group as a reference
category. Biochemically, the HIV-helminth coinfected group was associated with a
significantly higher total protein, higher percentage of transferrin saturation,
and significantly lower ferritin. There was no significant association between
single or dual infections with HIV and helminths with micro- and macronutrient
deficiency; however general obesity and low micronutrient intake patterns, which
may indicate a general predisposition to micronutrient and protein-energy
deficiency, were observed and may need further investigations.
PMID- 28421204
TI - Diabetic Cardiomyopathy: Current Approach and Potential Diagnostic and
Therapeutic Targets.
AB - Although ischemic heart disease is the major cause of death in diabetic patients,
diabetic cardiomyopathy (DCM) is increasingly recognized as a clinically relevant
entity. Considering that it comprises a variety of mechanisms and effects on
cardiac function, increasing the risk of heart failure and worsening the
prognosis of this patient category, DCM represents an important complication of
diabetes mellitus, with a silent development in its earlier stages, involving
intricate pathophysiological mechanisms, including oxidative stress, defective
calcium handling, altered mitochondrial function, remodeling of the extracellular
matrix, and consequent deficient cardiomyocyte contractility. While DCM is common
in diabetic asymptomatic patients, it is frequently underdiagnosed, due to few
diagnostic possibilities in its early stages. Moreover, since a strategy for
prevention and treatment in order to improve the prognosis of DCM has not been
established, it is important to identify clear pathophysiological landmarks, to
pinpoint the available diagnostic possibilities and to spot potential therapeutic
targets.
PMID- 28421205
TI - The Preferential Impairment of Pupil Constriction Stimulated by Blue Light in
Patients with Type 2 Diabetes without Autonomic Neuropathy.
AB - The main aim of the present paper is to examine whether the pupillary light
reflex (PLR) mediated by intrinsically photosensitive retinal ganglion cells
(ipRGCs) is impaired in type 2 diabetic patients. One hundred and three diabetic
patients without diabetic autonomic neuropathy (DAN) and 42 age-matched controls
underwent a series of detailed neurological examinations. The patients were
stratified into three groups: stage I, no neuropathy; stage II, asymptomatic
neuropathy; stage III, symptomatic but without DAN. The PLR to 470 and 635 nm
light at 20 cd/m2 was recorded. Small fiber neuropathy was assessed by corneal
confocal microscopy and quantifying corneal nerve fiber (CNF) morphology. The 470
nm light induced a stronger and faster PLR than did 635 nm light in all subjects.
The PLR to both lights was impaired equally across all of the diabetic subgroups.
The postillumination pupil response (PIPR) after 470 nm light offset at >=1.7 sec
was attenuated in diabetic patients without differences between subgroups.
Receiver operating characteristic analysis revealed that the PIPR mediated by
ipRGCs in patients with stage II and stage III neuropathy was different from that
of the control subjects. Clinical factors, nerve conduction velocity, and CNF
measures were significantly correlated with PLR parameters with 470 nm light. PLR
kinetics were more impaired by stimulation with blue light than with red light in
diabetic patients without DAN.
PMID- 28421206
TI - The Increased Circulating Plasma Levels of Vascular Endothelial Growth Factor in
Patients with Type 1 Diabetes Do Not Correlate to Metabolic Control.
AB - Aim. To characterize the plasma levels of vascular endothelial growth factor
(VEGF) in type 1 diabetes mellitus (T1D) and its relation to both present and
historical metabolic control and microvascular complications. Methods. Plasma
levels of VEGF and routine clinical parameters were analyzed in 115 patients with
long-standing T1D and 45 healthy controls (HC). All patients were under clinical
routine diabetes treatment at Uppsala University Hospital. Results. The plasma
levels of VEGF were increased by 37% in patients with T1D when compared to HC
(18.2 +/- 0.8 versus 13.2 +/- 1.0 pg/ml, p < 0.001). The levels of VEGF
correlated to insulin needs and BMI but not to present or historical metabolic
control. The levels of VEGF were similar in patients with T1D and microvascular
complications (microalbuminuria and retinopathy) when compared with patients
without microvascular complications. Historical HbA1c levels were found to be the
best predictor for present metabolic control. Conclusion. Circulating plasma
levels of VEGF do not correlate to present or historical metabolic control in
long-standing T1D and the levels are not affected by the presence of
microvascular complications.
PMID- 28421208
TI - Enhancing Tumor Detection in IR-UWB Breast Cancer System.
AB - An ultra-wideband (UWB) microwave system for breast cancer detection is
presented. The proposed system includes monocycle pulse generator, antipodal
Vivaldi antenna, breast model, and calibration algorithm for tumor detection.
Firstly, our pulse generator employs transmission gate in glitch generator to
achieve several advantages such as low power consumption and low ringing level.
Secondly, the antipodal Vivaldi antenna is designed assuming FR4 dielectric
substrate material, and developed antenna element (80 * 80 mm2) features a -10 dB
return loss and bandwidth ranges from 2.3 GHz to more than 11 GHz. Thirdly, the
phantom breast can be modeled as a layer of skin, fat, and then tumor is inserted
in this layer. Finally, subtract and add algorithm (SAD) is used as a calibration
algorithm in tumor detection system. The proposed system suggested that
horizontal antenna position with 90 degrees between transmitting and receiving
antennas is localized as a suitable antenna position with different rotating
location and a 0.5 cm near to phantom. The mean advantages of this localization
and tracking position around breast is a high received power signal approximately
around mv as a higher recognized signal in tumor detection. Using our proposed
system we can detect tumor in 5 mm diameter.
PMID- 28421207
TI - Detection of Human Papillomavirus Genotypes and Epstein-Barr Virus in
Nasopharyngeal Carcinomas at the Korle-Bu Teaching Hospital, Ghana.
AB - Nasopharyngeal carcinomas (NPC) are endemic in Far East Asia and commonly harbour
Epstein-Barr virus (EBV) which is known to serve as a key oncogenic promoter.
Human papillomavirus (HPV) is known to contribute to the pathogenesis of NPC.
However, in Ghana these two viruses have not been linked to NPC prevalence. This
study was designed to determine the HPV genotypes and EBV involved in NPC tissue
biopsies. A retrospective study design involving 72 formalin-fixed paraffin
embedded tissue (FFPET) samples of NPC from 2006 to 2012 were retrieved from the
Department of Pathology, University of Ghana School of Biomedical and Allied
Health Sciences. Sections were taken for histological analysis and for DNA lysate
preparation. The DNA lysates were subjected to polymerase chain reaction (PCR)
analysis to determine the presence of HPV genotypes and EBV. HPV specific primers
were used to type for fourteen HPV genotypes (HPV-16, 18, 6/11, 31, 33, 35, 44,
42, 43, 45, 56, 52, 58, and 59). Out of the 72 NPC biopsies analyzed by PCR, EBV
DNA was present in 18 (25%) cases and HPV DNA in 14 (19.23%). High risk HPV (HR
HPV) genotypes 18 and 31 were associated with the NPC. There were 3 (4.2%) cases
of coinfection by both viruses. The EBV DNA present in the undifferentiated
variant of the NPC and the histopathology of the NPC in Ghana is similar to the
type described in endemic areas.
PMID- 28421209
TI - Excitation dynamics involving homogeneous multistate interactions: one and two
color VMI and REMPI of HBr.
AB - Velocity map imaging (VMI) data and mass resolved REMPI spectra are
complementarily utilized to elucidate the involvement of homogeneous multistate
interactions in excited state dynamics of HBr. The H1Sigma+(v' = 0) and
E1Sigma+(v' = 1) Rydberg states and the V1Sigma+(v'= m + 7) and V1Sigma+(v'= m +
8) ion-pair states are explored as a function of rotational quantum number in the
two-photon excitation region of 79 100-80 700 cm-1. H+ and Br+ images were
recorded by one- as well as two-color excitation schemes. Kinetic energy release
(KER) spectra and angular distributions were extracted from the data. Strong-to
medium interactions between the E(1) and V(m + 8)/V(m + 7) states on one hand and
the H(0) and V(m + 7)/V(m + 8) states on the other hand were quantified from peak
shifts and intensity analysis of REMPI spectra. The effects of those interactions
on subsequent photoionization and photolytic pathways of HBr were evaluated in
one-color VMI experiments of the H+ and two-color VMI experiments of the Br+
photoproducts.
PMID- 28421210
TI - More accurate depiction of adsorption energy on transition metals using work
function as one additional descriptor.
AB - The reaction mechanism and properties of a catalytic process are primarily
determined by the interactions between reacting species and catalysts. However,
the interactions are often challenging to be experimentally measured, especially
for unstable intermediates. Therefore, it is of significant importance to
establish an exact relationship between chemical-catalyst interactions and
catalyst parameters, which will allow calculation of these interactions and thus
advance their mechanistic understanding. Herein we report the description of
adsorption energy on transition metals by considering both ionic bonding and
covalent bonding contributions and introduce the work function as one additional
responsible parameter. We find that the adsorption energy can be more accurately
described using a two-dimensional (2D) polynomial model, which shows a
significant improvement compared with the current adsorption energy-d-band center
linear correlation. We also demonstrate the utilization of this new 2D polynomial
model to calculate oxygen binding energy of different transition metals to help
understand their catalytic properties in oxygen reduction reactions.
PMID- 28421211
TI - Bioinspired carbide-derived carbons with hierarchical pore structure for the
adsorptive removal of mercury from aqueous solution.
AB - Biosilica of the diatom species Thalassiosira pseudonana is used as hard template
for the synthesis of silicon carbide-derived carbons. The typical species
specific macroporous structure is retained during the nanocasting-chlorine
treatment process and the resulting materials exhibit very high specific surface
areas up to 2300 m2 g-1. Bioinspired carbons show very high capacities in mercury
adsorption from aqueous solution compared to reference materials.
PMID- 28421212
TI - Cp*Co(iii)-catalyzed ortho-amidation of azobenzenes with dioxazolones.
AB - Cp*Co(iii)-catalyzed C-H amidation of azobenzene with dioxazolones has been
developed. The amidation reaction does not require external oxidants and gives
carbon dioxide as the only by-product. Both symmetrical and unsymmetrical
azobenzenes were found to undergo amidation smoothly with broad functional group
tolerance.
PMID- 28421213
TI - Nearest-neighbour nanocrystal bonding dictates framework stability or collapse in
colloidal nanocrystal frameworks.
AB - Block copolymers serve as architecture-directing agents for the assembly of
colloidal nanocrystals into a variety of mesoporous solids. Here we report the
fundamental order-disorder transition in such assemblies, which yield, on one
hand, ordered colloidal nanocrystals frameworks or, alternatively, disordered
mesoporous nanocrystal films. Our determination of the order-disorder transition
is based on extensive image analysis of films after thermal processing. The
number of nearest-nanocrystal neighbours emerges as a critical parameter
dictating assembly outcomes, which is in turn determined by the nanocrystal
volume fraction (fNC). We also identify the minimum fNC needed to support the
structure against collapse.
PMID- 28421214
TI - Hybrid molecular/enzymatic catalytic cascade for complete electro-oxidation of
glycerol using a promiscuous NAD-dependent formate dehydrogenase from Candida
boidinii.
AB - Glycerol is a common fuel considered for bioenergy applications. Computational
docking studies were performed on formate dehydrogenase from Candida boidinii
(cbFDH) that showed that mesoxalate can bind to the buried active site of the
holo form predicting that mesoxalate, a byproduct of glycerol oxidation, may act
as its substrate. Spectroscopic assays and characterization by HPLC and GC/TCD
have shown for the first time that cbFDH can act as a decarboxylase with
mesoxalate. From this assessment, cbFDH was combined with NH2-TEMPO to form a
novel hybrid anode to oxidize glycerol to carbon dioxide at near-neutral pH.
PMID- 28421215
TI - Control of supramolecular nanoassemblies by tuning the interactions of bent
shaped rod-coil molecules.
AB - Rod-coil molecules 1a, 1b and 2a, 2b, consisting of biphenyl and phenyl units
connected by an acetylene bond as the rod segment and oligo(ethylene glycol)
(OEG) as the coil segment, were synthesized and characterized. Molecules 1a and
1b incorporate a butoxy group at the apex of their bent-shaped rigid building
blocks, while both 1b and 2b contain a lateral methyl group between the rod and
coil segments. The self-assembling behavior of these molecules was investigated
using DSC, SAXS, CD, AFM, and TEM in bulk and aqueous solutions. In the bulk
state, 1a self-assembles into oblique columnar structures, whereas 1b,
incorporating butoxy and lateral methyl groups, self-assembles into three
dimensional body-centered tetragonal structures. Molecules 2a and 2b with no
butoxy groups, and 2b incorporating a lateral methyl group, self-assemble into
hexagonal perforated lamellar and oblique columnar structures, respectively. In
dilute aqueous solutions, 1a assembles into tubular nanoassemblies, while 1b self
organizes into micelles and nanoparticles. On the other hand, 2a and 2b
spontaneously aggregate into nanoribbons and nanofibers. Furthermore, CD
experiments together with AFM investigations of 2b indicate the creation of self
organized helical fibers, implying that the lateral methyl group induces the
helical stacking of the rod building block. These results reveal that the butoxy
and lateral methyl groups between the rod and coil segments dramatically
influence the creation of supramolecular nanostructures and morphologies.
PMID- 28421216
TI - Kinetics of crystalline nuclei growth in glassy systems.
AB - In this work, we study crystalline nuclei growth in glassy systems, focusing
primarily on the early stages of the process, during which the size of a growing
nucleus is still comparable with the critical size. On the basis of molecular
dynamics simulation results obtained for two crystallizing glassy systems, we
evaluate the growth laws of the crystalline nuclei and the parameters of the
growth kinetics at temperatures corresponding to deep supercooling; herein, a
statistical treatment of the simulation results is carried out using the mean
first-passage-time method. It is found that for the considered systems at
different temperatures, the crystal growth laws that were rescaled onto the
waiting times of the critically-sized nuclei follow a unified dependence, and can
significantly simplify the theoretical description of the post-nucleation growth
of crystalline nuclei. The evaluated size-dependent growth rates are
characterized by a transition to the steady-state growth regime, which depends on
the temperature and occurs in the glassy systems when the size of a growing
nucleus becomes two-three times larger than the critical size. It is suggested
that the temperature dependencies of the crystal growth rate characteristics
should be considered by using the reduced temperature scale T[combining tilde].
Thus, it is revealed that the scaled values of the crystal growth rate
characteristics (namely, the steady-state growth rate and the attachment rate for
the critically-sized nucleus) as functions of the reduced temperature T[combining
tilde] for glassy systems follow unified power-law dependencies. This finding is
supported by the available simulation results; the correspondence with the
experimental data for the crystal growth rates in glassy systems at temperatures
near the glass transition is also discussed.
PMID- 28421217
TI - Lighting-up breast cancer cells by a near-infrared fluorescent probe based on
KIAA1363 enzyme-targeting.
AB - The first NIR KIAA1363-targeting probe, NB-AX, specifically and instantly
featured an "off-on" switch upon gradual addition of KIAA1363 over all kinds of
other biomolecules, and its detection limit was initially calculated to be 0.58
MUg mL-1 (3delta/k). The probe was also able to be used in ultrafast
distinguishing of breast cancer cells from normal cells in fluorescence imaging
and applied in tissue imaging and tumor imaging in vivo.
PMID- 28421218
TI - Catalytic C-H amination driven by intramolecular ligand-to-nitrene one-electron
transfer through a rhodium(iii) centre.
AB - Werner type six-coordinate rhodium(iii) complexes coordinated by a planar
trianionic ligand and two axial aniline ligands are synthesised. The trianionic
ligand behaves as a redox-active ligand to form a ligand radical species upon one
electron oxidation of the complex. The rhodium(iii) complexes catalyse C-H
amination of external substrates such as xanthene with tosylazide as the nitrene
source. DFT-calculation and kinetic deuterium isotope effects indicate that a di
radical rhodium(iii) complex formed by one-electron transfer from the redox
active ligand to the nitrene group works as a reactive intermediate to induce
aliphatic C-H activation.
PMID- 28421219
TI - Kinetic resolution via supramolecular iminium catalysis: multiactivation enables
the asymmetric synthesis of beta-aryl substituted aldehydes and densely
functionalized cyclohexanes.
AB - The kinetic resolution of beta-aryl substituted 1,7-dioxo compounds with
alpha,beta-unsaturated aldehydes affording enantioenriched beta-aryl substituted
aldehydes as well as densely functionalized cyclohexanes is presented. The two
enantioenriched products were obtained in reasonable yields with high diastereo-
and enantioselectivities under supramolecular iminium catalysis which activates
both the substrates and the reactive intermediates.
PMID- 28421220
TI - A highly selective, colorimetric, and environment-sensitive optical potassium ion
sensor.
AB - Potassium ions (K+) play vital roles in many biological processes and thus highly
selective sensors for K+ are critical for disease diagnosis and health
monitoring. Herein, we report a colorimetric K+ sensor (KS7) in which a
hemicyanine dye was used as a fluorophore and phenylaza-[18]crown-6 lariat ether
(ACLE) was utilized as a K+ ligand. The maximum absorption peak of KS7 shifted
hypsochromically by 77 nm (from 515 to 438 nm) with an isosbestic point at 452 nm
upon the addition of K+ to its aqueous solution accompanied by a color change
from red to yellow. This sensor exhibited a linear response range to K+ from 1 to
200 mM, indicating its wide detection range for cellular, urinary, and
environmental potassium ions. Further, this sensor is solvent-sensitive, implying
its environmental sensitivity. For the demonstration of its applications, we
prepared filter paper-based K+ test strips, which were used to detect K+ in urine
conveniently.
PMID- 28421221
TI - Retraction: Synthesis and facet-dependent photocatalytic activity of BiOBr single
crystalline nanosheets.
AB - Retraction of 'Synthesis and facet-dependent photocatalytic activity of BiOBr
single-crystalline nanosheets' by Wenwen Lin et al., Chem. Commun., 2014, DOI:
10.1039/c3cc41498a
PMID- 28421222
TI - Novel photocatalysts: general discussion.
PMID- 28421223
TI - Selectivity of quantum dot sensitized ZnO nanotube arrays for improved
photocatalytic activity.
AB - In this work, PbS/ZnO, CdS/ZnO and CdSe/ZnO hierarchical heterostructures have
been successfully synthesized by combining water bath and chemical bath
deposition (CBD) methods on indium-doped tin oxide (ITO). Scanning electron
microscopy (SEM) results show that quantum dots (QDs) certainly form on the pre
grown ZnO nanorod (NR) and nanotube (NT) arrays. The amount of QDs capped on ZnO
could be regulated by varying the cycle times. The photocatalytic activity of the
QD-sensitized ZnO is investigated by decomposition of methyl orange (MO) under
irradiation, which show remarkable enhancement compared to bare ZnO. The ZnO NTs
sensitized by PbS QDs have the highest catalytic activity among the three QDs
(PbS, CdS and CdSe QDs). The UV-vis absorption diagrams and the Ct/C0 curves
reveal that 8PbS/ZnO NTs have the highest catalytic activity, which can degrade
MO (20 mg L-1) into a colorless solution within 30 min. Meanwhile, the synthetic
methodology described herein provides an effective approach for fabricating a
variety of photocatalysts. The heterostructured nanomaterials have significant
potential to solve environmental and energy issues.
PMID- 28421224
TI - Chirality-induced helical self-propulsion of cholesteric liquid crystal droplets.
AB - We report the first experimental realization of a chiral artificial microswimmer
exhibiting helical motion without any external fields. We discovered that a
cholesteric liquid crystal (CLC) droplet with a helical director field swims in a
helical path driven by the Marangoni flow in an aqueous surfactant solution. We
also showed that the handedness of the helical path is reversed when that of the
CLC droplet is reversed by replacing the chiral dopant with the enantiomer. In
contrast, nematic liquid crystal (NLC) droplets exhibited ballistic motions.
These results suggest that the helical motion of the CLC droplets is driven by
chiral couplings between the Marangoni flow and rotational motion via the helical
director field of CLC droplets.
PMID- 28421225
TI - Using telephony data to facilitate discovery of clinical workflows.
AB - BACKGROUND: Discovery of clinical workflows to target for redesign using methods
such as Lean and Six Sigma is difficult. VoIP telephone call pattern analysis may
complement direct observation and EMR-based tools in understanding clinical
workflows at the enterprise level by allowing visualization of institutional
telecommunications activity. OBJECTIVE: To build an analytic framework mapping
repetitive and high-volume telephone call patterns in a large medical center to
their associated clinical units using an enterprise unified communications server
log file and to support visualization of specific call patterns using graphical
networks. METHODS: Consecutive call detail records from the medical center's
unified communications server were parsed to cross-correlate telephone call
patterns and map associated phone numbers to a cost center dictionary. Hashed
data structures were built to allow construction of edge and node files
representing high volume call patterns for display with an open source graph
network tool. RESULTS: Summary statistics for an analysis of exactly one week's
call detail records at a large academic medical center showed that 912,386 calls
were placed with a total duration of 23,186 hours. Approximately half of all
calling called number pairs had an average call duration under 60 seconds and of
these the average call duration was 27 seconds. CONCLUSIONS: Cross-correlation of
phone calls identified by clinical cost center can be used to generate graphical
displays of clinical enterprise communications. Many calls are short. The compact
data transfers within short calls may serve as automation or re-design targets.
The large absolute amount of time medical center employees were engaged in VoIP
telecommunications suggests that analysis of telephone call patterns may offer
additional insights into core clinical workflows.
PMID- 28421226
TI - Portable LED-induced autofluorescence spectroscopy for oral cancer diagnosis.
AB - Oral cancer is a serious and growing problem in many developing and developed
countries. To improve the cancer screening procedure, we developed a portable
light-emitting-diode (LED)-induced autofluorescence (LIAF) imager that contains
two wavelength LED excitation light sources and multiple filters to capture ex
vivo oral tissue autofluorescence images. Compared with conventional means of
oral cancer diagnosis, the LIAF imager is a handier, faster, and more highly
reliable solution. The compact design with a tiny probe allows clinicians to
easily observe autofluorescence images of hidden areas located in concave deep
oral cavities. The ex vivo trials conducted in Taiwan present the design and
prototype of the portable LIAF imager used for analyzing 31 patients with 221
measurement points. Using the normalized factor of normal tissues under the
excitation source with 365 nm of the central wavelength and without the bandpass
filter, the results revealed that the sensitivity was larger than 84%, the
specificity was not smaller than over 76%, the accuracy was about 80%, and the
area under curve of the receiver operating characteristic (ROC) was achieved at
about 87%, respectively. The fact shows the LIAF spectroscopy has the
possibilities of ex vivo diagnosis and noninvasive examinations for oral cancer.
PMID- 28421227
TI - Multiple, Fine, Firm Keratotic Papules on the Palms: A Quiz.
PMID- 28421228
TI - Extraordinary Findings in a Case of Self-inflicted Cutaneous Lesions.
PMID- 28421229
TI - Atypical Trigeminal Trophic Syndrome: An Unusual Cause of Facial Ulceration.
PMID- 28421230
TI - Locally Aggressive Trichoblastic Tumours (Low-grade Trichoblastic Carcinomas):
Clinicopathological Analysis and Follow-up.
PMID- 28421231
TI - Periorbital Involvement in Early Stage Mycosis Fungoides.
PMID- 28421232
TI - Clinical Spectrum, Quality of Life, BRAF Mutation Status and Treatment of Skin
Involvement in Adult Langerhans Cell Histiocytosis.
AB - Langerhans cell histiocytosis is a rare histiocytic disorder for which skin
involvement and management are poorly described in adults. The aim of this
retrospective monocentric study in a national reference centre is to describe the
clinical characteristics, quality of life, BRAF mutation status and outcomes of
skin involvement in adult patients with Langerhans cell histiocytosis. Twenty
five patients (14 females, mean age 47 years) were included, with a median follow
up of 33 months (range 4-420 months). Patients experienced poor dermatological
quality of life despite low body surface involvement. BRAFV600 mutations were
detected in 8 of the 18 patients analysed (45%). Eight patients had an associated
malignancy. Several treatment options were used and consisted of surgery, topical
steroids and carmustine, thalidomide, methotrexate, vinblastine and steroids and
cladribine. This study highlights the need to evaluate quality of life and to
screen for associated malignancy in adult patients with Langerhans cell
histiocytosis.
PMID- 28421233
TI - Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with
Gene Polymorphism Suggests a Role in Disease Pathogenesis.
AB - CD93 is involved in angiogenesis and inflammation, both of which are key
processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral
blood mononuclear cells and skin of patients with psoriasis and controls.
Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms
rs2749812 and rs2749817 were assessed in patients with psoriasis compared with
controls and the effect of narrowband ultraviolet B (NB-UVB) treatment on CD93
gene expression was evaluated in the skin of patients with psoriasis. CD93 gene
expression was significantly increased in lesional and non-lesional skin from
patients with psoriasis compared with controls. Immunohistochemistry revealed
CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was
significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment
of patients with psoriasis did not alter skin CD93 gene expression. Increased
protein expression of CD93 psoriatic skin and association with the rs2749817
polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.
PMID- 28421234
TI - The Role of Topical Timolol in the Treatment of Infantile Hemangiomas: A
Systematic Review and Meta-analysis.
AB - To date the efficacy and safety of topical timolol in the treatment of infantile
hemangioma has not been reviewed and analysed systematically. We collated all
published data on the efficacy and safety of topical timolol in the treatment of
infantile hemangioma. A total of 31 studies with 691 patients were included. The
fixed effects pooled estimate of the response rate defined as any improvement
from baseline of infantile hemangioma after treatment with topical timolol was
significant (RR = 8.96; 95% CI 5.07-15.47; heterogeneity test p = 0.99), and the
treatment was overall well tolerated. However, the quality of evidence was low to
moderate. Topical timolol is an effective treatment for small infantile
hemangioma, with no significant adverse effects noted. However, there is still a
need for adequately powered randomised controlled trials.
PMID- 28421235
TI - Koebner Phenomenon in Eosinophilic Granulomatosis with Polyangiitis (Churg
Strauss).
PMID- 28421236
TI - Uncommon Presentation of Scleromyxoedema with a Distribution Pattern Mimicking a
Photodermatosis.
PMID- 28421237
TI - Radiographic interpretation of carpometacarpal arthroplasty: correlation between
radiographic loosening and clinical outcome.
AB - OBJECTIVE: To assess the radiographic appearance and interpretation of loosening
in patients following first carpometacarpal joint pyrohemisphere arthroplasty.
MATERIALS AND METHODS: A retrospective review over a 6-year period was performed
identifying patients with first carpometacarpal pyrohemisphere implants. All
postoperative radiographs were reviewed and compared with clinical information.
Loosening was defined as greater than 1 mm of periprosthetic lucency or
increasing lucency on serial studies. Adverse clinical outcome was defined as
infection, complex regional pain syndrome, subluxation or an inability to return
to activities of daily living. Statistical analysis included Cohen's Kappa
coefficient to measure inter-reader agreement for radiographic interpretation and
the agreement between radiographic loosening and an undesired or adverse clinical
outcome. RESULTS: Thirty-one implants in 26 patients were reviewed. A total of 73
postoperative radiographs were reviewed. The mean age of the study subjects was
58 years. The mean radiographic follow-up was 13 months (range: 1-56). All
arthroplasties were performed for osteoarthritis. Only one repeat surgery was
performed. There was good agreement amongst readers with regard to radiographic
interpretation, but the strength of agreement between radiographic loosening and
adverse clinical outcome was poor. The sensitivity of radiography in predicting
an adverse clinical outcome was 63%, specificity 65%, positive predictive value
39%, and negative predictive value 83%. CONCLUSION: Although radiography may be
useful in the correct clinical context, it should not be utilized as the sole
predictor of adverse clinical outcomes following carpometacarpal arthroplasty.
PMID- 28421238
TI - The impact of low education and poor health on unemployment varies by work life
stage.
AB - OBJECTIVES: The aim of this study is to examine associations and interactions of
education, and physical and mental health with unemployment in early, mid, and
late work life. METHODS: This cross-sectional study uses data from 69,118
respondents from Lifelines. Health status was measured with the RAND-36,
education was self-reported, and participants working <12 h per week or
indicating to be unemployed were considered unemployed. The relative excess risk
due to interaction (RERI) was calculated to measure interaction on the additive
scale. RESULTS: Interactions of low education and poor mental health were found
in early [RERI: 2.14; 95% confidence interval (CI): 0.63, 3.65], mid (1.41; 0.61,
2.20) and late (0.63; 0.09, 1.17) work life. Interaction between low education
and poor physical health was only found in mid-work life (1.27; 0.61, 1.93).
CONCLUSIONS: Low education and poor physical and mental health exacerbate each
other's impact on unemployment varying by work life stage. Policies addressing
unemployment may become more effective if they better account for the physical
and mental health status of adults in certain stages of their work life.
PMID- 28421239
TI - Weight-bearing recommendations after operative fracture treatment-fact or
fiction? Gait results with and feasibility of a dynamic, continuous
pedobarography insole.
AB - PURPOSE: Rehabilitation after lower-extremity fractures is based on the
physicians' recommendation for non-, partial-, or full weight-bearing. Clinical
studies rely on this assumption, but continuous compliance or objective loading
rates are unknown. The purpose of this study was to determine the compliance to
weight-bearing recommendations by introducing a novel, pedobarography system
continuously registering postoperative ground forces into ankle, tibial shaft and
proximal femur fracture aftercare and test its feasibility for this purpose.
METHODS: In this prospective, observational study, a continuously measuring
pedobarography insole was placed in the patients shoe during the immediate post
operative aftercare after ankle, tibial shaft and intertrochanteric femur
fractures. Weight-bearing was ordered as per the institutional standard and
controlled by physical therapy. The insole was retrieved after a maximum of six
weeks (28 days [range 5-42 days]). Non-compliance was defined as a failure to
maintain, or reach the ordered weight-bearing within 30%. RESULTS: Overall 30
patients were included in the study. Fourteen (47%) of the patients were
compliant to the weight-bearing recommendations. Within two weeks after surgery
patients deviated from the recommendation by over 50%. Sex, age and weight did
not influence the performance (p > 0.05). Ankle fracture patients (partial weight
bearing) showed a significantly increased deviation from the recommendation (p =
0.01). CONCLUSIONS: Our study results show that, despite physical therapy
training, weight-bearing compliance to recommended limits was low. Adherence to
the partial weight-bearing task was further decreased over time. Uncontrolled
weight-bearing recommendations should thus be viewed with caution and carefully
considered as fiction. The presented insole is feasible to determine weight
bearing continuously, could immediately help define real-time patient behaviour
and establish realistic, individual weight-bearing recommendations.
PMID- 28421241
TI - Effect of methyl-beta-cyclodextrin on gene expression in microbial conversion of
phytosterol.
AB - Modified beta-cyclodextrins are widely used for the enhancement of microbial
conversions of lipophilic compounds such as steroids. Multiple mechanisms of
cyclodextrin-mediated enhancement of phytosterol bioconversion by mycobacteria
had previously been shown to include steroid solubilization, alterations in the
cell wall permeability for both steroids and nutrients, facilitation of protein
leaking, and activity suppression of some steroid-transforming enzymes.In this
work, we studied whether cyclodextrins might affect expression of the genes
involved in the steroid catabolic pathway. Phytosterol bioconversion with 9alpha
hydroxy-androst-4-ene-3,17-dione accumulation by Mycobacterium sp. VKM Ac-1817D
in the presence of methylated beta-cyclodextrin (MCD) was investigated. RNA
sequencing of the whole transcriptomes in different combinations of phytosterol
and MCD showed a similar expression level of the steroid catabolism genes related
to the KstR-regulon and was responsible for side chain and initial steps of
steroid core oxidation; whereas, induction levels of the genes related to the
KstR2-regulon were attenuated in the presence of MCD in this strain. The data
were attenuated with quantitative real-time PCR.The results contribute to the
understanding of cyclodextrin effects on microbial steroid conversion and provide
a basis for the use of cyclodextrins as expression enhancers for studies of
sterol catabolism in actinobacteria.
PMID- 28421240
TI - A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel
and prednisone versus docetaxel and prednisone alone in castration-resistant
prostate cancer (CRPC) metastatic to bone; the Taxium II trial.
AB - BACKGROUND: Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for
palliation of metastatic bone pain. We investigated whether the addition of
rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in
patients with CRPC. METHODS: Patients with progressive CRPC and osteoblastic bone
metastases were randomised for first-line docetaxel 75 mg/m2 3-weekly plus
prednisone with or without 2 injections of rhenium-188-HEDP after the third (40
MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was
progression-free survival (PFS), defined as either PSA, radiographic or clinical
progression. Patients were stratified by extent of bone metastases and hospital.
RESULTS: Forty-two patients were randomised for standard treatment and 46
patients for combination therapy. Median number of cycles of docetaxel was 9 in
the control group and 8 in the experimental group. Median follow-up was 18.4
months. Two patients from the experimental group did not start treatment after
randomisation. In the intention to treat analysis no differences in PFS, survival
and PSA became apparent between the two groups. In an exploratory per-protocol
analysis median overall survival was significantly longer in the experimental
group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months
(95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline
phosphatase >220U/L was significantly better with combination treatment (9.0
months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005).
As expected, thrombocytopenia (grade I/II) was reported more frequently in the
experimental group (25% versus 0%). CONCLUSION: Combined treatment with rhenium
188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed
survival benefit in the per-protocol analysis warrants further studies in the
combined treatment of chemotherapy and radiopharmaceuticals.
PMID- 28421242
TI - CT features of hepatic metastases from hepatoid adenocarcinoma.
AB - PURPOSE: The purpose of this study was to report the imaging presentation of
hepatic metastases from hepatoid adenocarcinoma (HAC). METHODS: We
retrospectively identified 11 patients (10 men and 1 woman; median age 66) with
HAC liver metastasis who underwent contrast-enhanced computed tomography (CT)
which included arterial phase and portal venous phase. Two radiologists analyzed
the imaging parameters, which included the enhancement pattern on arterial and
portal phase images, necrosis, venous thrombi, and overall imaging diagnosis, and
arrived at a consensus. RESULTS: On arterial phase, the liver lesions had global
hyper-enhancement (n = 0), heterogeneous hyper-enhancement (63.6%; n = 7/11),
peripheral hyper-enhancement (n = 0), iso-enhancement (n = 0/11), or hypo
enhancement (36.4%; n = 4/11). On portal venous phase, homogenous hypo
enhancement (18.2%; n = 2/11) and heterogenous hypo-enhancement (81.8%; n = 9/11)
were observed. Venous thromboses occurred in four patients (36.4%; n = 4/11). The
overall imaging diagnoses were "HCC-like" in seven patients (63.6%; n = 7/11),
"indeterminable" in 1 patient (9.1%; n = 1/11), and "HCC-unlike" in three
patients (27.3%; n = 3/11). CONCLUSIONS: The imaging features of HAC liver
metastasis were varied. Arterial phase enhancement coupled with venous phase
washout (resembling HCC imaging features) was a major finding, but arterial phase
hypo-enhancement (distinct from HCC imaging features) was also frequently
encountered.
PMID- 28421243
TI - Assessment of 70-keV virtual monoenergetic spectral images in abdominal CT
imaging: A comparison study to conventional polychromatic 120-kVp images.
AB - PURPOSE: To evaluate the image quality of 70-keV virtual monoenergetic (monoE)
abdominal CT images compared to 120-kVp polychromatic images generated from a
spectral detector CT (SDCT) scanner. METHODS: This prospective study included
generation of a 120-kVp polychromatic dataset and a 70-keV virtual monoE dataset
after a single contrast-enhanced CT acquisition on a SDCT scanner (Philips
Healthcare) during portal venous phase. The attenuation values (HU), noise,
signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured in
the liver, spleen, pancreas, kidney, aorta, portal vein, and muscle. The
subjective image quality including noise, soft tissue contrast, sharpness, and
overall image quality were graded on a 5-point Likert scale by two radiologists
independently (1-worst image quality, 5-best image quality). Statistical analysis
was performed using paired sample t test and Fleiss's Kappa. RESULTS: Fifty-five
patients (54.3 +/- 16.8 y/o; 28 M, 27 F) were recruited. The noise of target
organs was significantly lower in virtual monoE images in comparison to
polychromatic images (p < 0.001). The SNR and CNR were significantly higher in
virtual monoE images (p < 0.001 for both). Subjective image quality of 70-keV
virtual monoE images was significantly better (p < 0.001) for all evaluated
parameters. Median scores for all subjective parameters were 3.0 versus 4.0 for
polychromatic vs virtual monoE images, respectively. The inter-reader agreement
for overall image quality was good (Kappa were 0.767 and 0.762 for polychromatic
and virtual monoE images, respectively). CONCLUSION: In abdominal imaging, 70-keV
virtual monoE CT images demonstrated significantly better noise, SNR, CNR, and
subjective score compared to conventional 120-kVp polychromatic images.
PMID- 28421244
TI - Texture analysis as a radiomic marker for differentiating renal tumors.
AB - PURPOSE: To evaluate the utility of texture analysis for the differentiation of
renal tumors, including the various renal cell carcinoma subtypes and oncocytoma.
MATERIALS AND METHODS: Following IRB approval, a retrospective analysis was
performed, including all patients with pathology-proven renal tumors and an
abdominal computed tomography (CT) examination. CT images of the tumors were
manually segmented, and texture analysis of the segmented tumors was performed. A
support vector machine (SVM) method was also applied to classify tumor types.
Texture analysis results were compared to the various tumors and areas under the
curve (AUC) were calculated. Similar calculations were performed with the SVM
data. RESULTS: One hundred nineteen patients were included. Excellent
discriminators of tumors were identified among the histogram-based features
noting features skewness and kurtosis, which demonstrated AUCs of 0.91 and 0.93
(p < 0.0001), respectively, for differentiating clear cell subtype from
oncocytoma. Histogram feature median demonstrated an AUC of 0.99 (p < 0.0001) for
differentiating papillary subtype from oncocytoma and an AUC of 0.92 for
differentiating oncocytoma from other tumors. Machine learning further improved
the results achieving very good to excellent discrimination of tumor subtypes.
The ability of machine learning to distinguish clear cell subtype from other
tumors and papillary subtype from other tumors was excellent with AUCs of 0.91
and 0.92, respectively. CONCLUSION: Texture analysis is a promising non-invasive
tool for distinguishing renal tumors on CT images. These results were further
improved upon application of machine learning, and support the further
development of texture analysis as a quantitative biomarker for distinguishing
various renal tumors.
PMID- 28421245
TI - Research in community-acquired pneumonia: the next steps.
PMID- 28421246
TI - Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT):
a randomised, blinded, placebo-controlled trial.
AB - PURPOSE: The aim of the INSTINCT trial was to assess the effect of intravenous
polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported
physical function in intensive care unit (ICU) patients with necrotising soft
tissue infection (NSTI). METHODS: We randomised 100 patients with NSTI 1:1 to
masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of
0.9% saline once daily for the first 3 days of ICU admission. The primary outcome
was the physical component summary (PCS) score of the 36-item short form health
survey (SF-36) 6 months after randomisation; patients who had died were given the
lowest possible score (zero). RESULTS: Of the 100 patients randomised, 87 were
included in the intention-to-treat analysis of the PCS score, 42 patients (84%)
in the IVIG group and 45 patients (90%) in the placebo group. The two
intervention groups had similar baseline characteristics with the exception of
IVIG use before randomisation (1 dose was allowed) and rates of acute kidney
injury. Median PCS scores were 36 (interquartile range 0-43) in the group
assigned to IVIG and 31 (0-47) in the group assigned to placebo (mean adjusted
difference 1 (95% confidence interval -7 to 10), p = 0.81). The result was
supported by analyses adjusted for baseline prognostics, those in the per
protocol populations, in the subgroups (site of NSTI) and those done post hoc
adjusted for IVIG use before randomisation. CONCLUSIONS: In ICU patients with
NSTI, we observed no apparent effects of adjuvant IVIG on self-reported physical
functioning at 6 months. TRIAL REGISTRATION: NCT02111161.
PMID- 28421247
TI - [Rare Diseases].
PMID- 28421248
TI - Indications for cellular migration from the central nervous system to its
draining lymph nodes in CD11c-GFP+ bone-marrow chimeras following EAE.
AB - The concept as to how the brain maintains its immune privilege has initially been
based on observations that it is lacking classical lymph vessels and later, the
absence of dendritic cells (DC). This view has been challenged by several groups
demonstrating drainage/migration of injected tracers and cells into cervical
lymph nodes (CLNs) and the presence of brain antigens in CLNs in the course of
various brain pathologies. Using CD11c-diphtheria toxin receptor (DTR)-green
fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of
CD11c+ cells, a main DC marker, within the brain parenchyma. Since injecting
tracers or cells may cause barrier artefacts, we have now transplanted wild type
(wt)-bone marrow (BM) to lethally irradiated CD11c-DTR-GFP tg mice to restrict
the CD11c-DTR-GFP+ population to the brain and induced experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We observed
ramified GFP+ cells in the olfactory bulb, the cribriform plate, the nasal mucosa
and superficial CLNs. We measured a significant increase of host gfp genomic DNA
(gDNA) levels in lymph nodes (LNs) previously described as draining stations for
the central nervous system (CNS). Using flow cytometry analysis, we observed an
increase of the percentage of CD11c-GFP+ cells in brain parenchyma in the course
of EAE which is most likely due to an up-regulation of CD11c of resident
microglial cells since levels of gfp gDNA did not increase. Our data supports the
hypothesis that brain-resident antigen presenting cells (APC) are capable of
migrating to CNS-draining LNs to present myelin-associated epitopes.
PMID- 28421249
TI - Co-effects of pyrene and nitrate on the activity and abundance of soil
denitrifiers under anaerobic condition.
AB - It has previously been confirmed that polycyclic aromatic hydrocarbons (PAHs)
could be degraded by soil microbes coupling with denitrification, but the
relationships among soil denitrifiers, PAHs, and nitrate under obligate anaerobic
condition are still unclear. Here, co-effects of pyrene and nitrate on the
activity and abundance of soil denitrifiers were investigated through a 45-day
incubation experiment. Two groups of soil treatments with (N30) and without (N0)
nitrate (30 mg kg-1 dry soil) amendment were conducted, and each group contained
three treatments with different pyrene concentrations (0, 30, and 60 mg kg-1 dry
soil denoted as P0, P30, and P60, respectively). The pyrene content, abundances
of denitrification concerning genes (narG, periplasmic nitrate reductase gene;
nirS, cd 1-nitrite reductase gene; nirK, copper-containing nitrite reductase
gene), and productions of N2O and CO2 were measured at day 3, 14, 28, and 45, and
the bacterial community structures in four represented treatments (N0P0, N0P60,
N30P0, and N30P60) were analyzed at day 45. The results indicated that the
treatments with higher pyrene concentration had higher final pyrene removal rates
than the treatments with lower pyrene concentration. Additionally, intensive
emission of N2O was detected in all treatments only at day 3, but a continuous
production of CO2 was measured in each treatment during the incubation. Nitrate
amendment could enhance the activity of soil denitrifiers, and be helpful for
soil microbes to sustain their activity. While pyrene seemed had no influence on
the productions of N2O and CO2, and amendment with pyrene or nitrate both had no
obvious effect on abundances of denitrification concerning genes. Furthermore, it
was nitrate but not pyrene had an obvious influence on the community structure of
soil bacteria. These results revealed that, under anaerobic condition, the
activity and abundance of soil denitrifiers both were insensitive to pyrene, but
nitrate could improve the activity of soil denitrfiers and induce the shifts in
soil bacterial community structure.
PMID- 28421250
TI - Erratum to: CX3CR1 deficiency accelerates the development of retinopathy in a
rodent model of type 1 diabetes.
PMID- 28421252
TI - Altitude Distributions and Source Analysis of OCPs and PCBs in Surface Soils of
Changbai Mountain, Northeast China.
AB - Organochlorine pesticides and polychlorinated biphenyls in surface soils of
Changbai Mountain, Northeastern China, have been quantified by gas chromatography
with electron capture detector and the altitude distributions and possible
pollution sources were analyzed. The concentrations of ?HCHs, ?DDTs and ?7PCBs
were in the range of 3.09-25.6, 0.96-19.4 and 7.32-26.1 ng/g dw, respectively.
The concentration of alpha-HCH, beta-HCH, p,p'-DDT, p,p'-DDE, PCB 101, 138, 153,
and 180 showed increasing trends with altitude. ?7PCBs in surface soils of
Changbai Mountain were significantly higher than that in Chinese background
areas. The concentration of lower volatile PCB isomers showed positive
correlation with altitude. These pollutants may originate from the adjacent
industrial and agricultural areas via atmospheric transport and cold-trapping
effect through wet precipitation. Additional, DDTs may cause a certain potential
ecological risks on birds and soil organisms and the usage of lindane in the
adjacent areas cannot be excluded in Changbai Mountain.
PMID- 28421251
TI - Defining the ultrasound longitudinal natural history of newly diagnosed pediatric
small bowel Crohn disease treated with infliximab and infliximab-azathioprine
combination therapy.
AB - BACKGROUND: Little is known about changes in the imaging appearances of the bowel
and mesentery over time in either pediatric or adult patients with newly
diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha
(anti-TNF-alpha) therapy. OBJECTIVE: To define how bowel ultrasound findings
change over time and correlate with laboratory inflammatory markers in children
who have been newly diagnosed with pediatric small bowel Crohn disease and
treated with infliximab. MATERIALS AND METHODS: We included 28 pediatric patients
treated with infliximab for newly diagnosed ileal Crohn disease who underwent
bowel sonography prior to medical therapy and at approximately 2 weeks, 1 month,
3 months and 6 months after treatment initiation; these patients also had
laboratory testing at baseline, 1 month and 6 months. We used linear mixed models
to compare mean results between visits and evaluate whether ultrasound
measurements changed over time. We used Spearman rank correlation to assess
bivariate relationships. RESULTS: Mean subject age was 15.3+/-2.2 years; 11
subjects were girls (39%). We observed decreases in mean length of disease
involvement (12.0+/-5.4 vs. 9.1+/-5.3 cm, P=0.02), maximum bowel wall thickness
(5.6+/-1.8 vs. 4.7+/-1.7 mm, P=0.02), bowel wall color Doppler signal (1.7+/-0.9
vs. 1.2+/-0.8, P=0.002) and mesenteric color Doppler signal (1.1+/-0.9 vs. 0.6+/
0.6, P=0.005) at approximately 2 weeks following the initiation of infliximab
compared to baseline. All laboratory inflammatory markers decreased at 1 month (P
values<0.0001). There was strong correlation between bowel wall color Doppler
signal and fecal calprotectin (rho=0.710; P<0.0001). Linear mixed models
confirmed that maximum bowel wall thickness (P=0.04), length of disease
involvement (P=0.0002) and bowel wall color Doppler signal (P<0.0001) change over
time in response to infliximab, when adjusted for age, sex, azathioprine therapy,
scanning radiologist and baseline short pediatric Crohn's disease activity index
score. CONCLUSION: The ultrasound appearance of the bowel changes as early as 2
weeks after the initiation of infliximab therapy. There is strong correlation
between bowel wall color Doppler signal and fecal calprotectin.
PMID- 28421253
TI - Levels and Sources of Organochlorine Pesticides in Surface Sediment from Anhui
Reach of Huaihe River, China.
AB - Twenty-two organochlorine pesticides (OCPs) were investigated in Anhui reach of
Huaihe river, China. Seventeen out of 22 OCPs were detected by GC-MS. The mean
concentrations of OCPs followed the order: HCHs > DDTs > HCB > chlordanes >
endosulfans. Levels of total HCHs and total DDTs ranged from 2.54 to 13.91 ng g-1
(mean = 7.52 ng g-1) and 0.016 to 2.54 ng g-1 (mean = 0.45 ng g-1), respectively.
The concentrations of DDTs were lower than those of HCHs. Compared with the other
rivers in China, DDTs and HCHs were relatively lower or similar. Statistical
analysis indicated that the OCPs concentration differences were not insignificant
between upstream, midstream and downstream. The compound compositions suggested
that historical usage of lindane and fresh DDT were the main sources. The
regression analysis indicated that TOC has influence on the levels of HCHs and
little influence on the levels of DDTs in the sediments.
PMID- 28421254
TI - [Scalp disorders].
PMID- 28421255
TI - [Tropical dermatology-relevant disorders of the scalp].
AB - People whose ancestors came from tropical regions present specific structural
characteristics of their skin and hair, including the scalp region. On the one
hand, this is for protection against the challenges of these climatic zones; on
the other hand, this may lead to an enhanced sensitivity against certain
dermatological diseases, either of autoimmune, chronic inflammatory, infectious,
or of mechanical origin. A collection of these are discussed in this article.
PMID- 28421256
TI - Special issue: recognizing the lifetime scientific contributions of Athina
Markou.
PMID- 28421257
TI - Histone deacetylase inhibitors reverse age-related increases in side effects of
haloperidol in mice.
AB - BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced
side effects, and the pharmacodynamic mechanism underlying this phenomenon
remains unclear. We hypothesized that age-related epigenetic alterations lead to
decreased expression and functionality of the dopamine D2 receptor (D2R),
contributing to this susceptibility. METHODS: In this study, we treated young (2
3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist
haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side
effects. In addition, we pretreated separate groups of young and aged mice with
histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275)
and then administered HAL. RESULTS: Our results show that the motor side effects
of HAL are exaggerated in aged mice as compared to young mice and that HDAC
inhibitors are able to reverse the severity of these deficits. HAL-induced motor
deficits in aged mice are associated with an age- and drug-dependent decrease in
striatal D2R protein levels and functionality. Further, histone acetylation was
reduced while histone tri-methylation was increased at specific lysine residues
of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC
inhibitors, particularly VPA, restored striatal D2R protein levels and
functionality and reversed age- and drug-related histone modifications at the
Drd2 promoter. CONCLUSIONS: These results suggest that epigenetic changes at the
striatal Drd2 promoter drive age-related increases in antipsychotic side effect
susceptibility, and HDAC inhibitors may be an effective adjunct treatment
strategy to reduce side effects in aged populations.
PMID- 28421258
TI - [Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation
with cochlear implants. German version].
AB - Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden
hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed
an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebello
pontine angle (CPA), 1 a transotic including the CPA and 1 a multilocular
location. The tumors were removed surgically in 9 patients, whereas 3 patients
opted for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3
underwent labyrinthectomy and cochlear implant (CI) surgery in a single stage
procedure; 1 patient received extended cochleostomy with CI surgery; 3 underwent
partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI
surgery (n = 1) or implantation of electrode dummies for possible later CI
following repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the
internal auditory canal and cerebellopontile angle exhibiting transmodiolar or
transmacular growth were removed by combined translabyrinthine-transotic
resection. For the intracochlear tumors, vestibular function could mostly be
preserved after surgery. In all cases with CI surgery, hearing rehabilitation was
successful, although speech discrimination was limited for the case with subtotal
cochleoectomy. Surgical removal of intracochlear schwannomas via partial or
subtotal cochleoectomy is, in principle, possible with preservation of vestibular
function. In the authors' opinion, radiotherapy of ILS is only indicated in
isolated cases. Provided performed early enough, cochlear implantation after
surgical removal of ILS is an option for auditory rehabilitation, thus
representing-in contrast to the "wait-and-test-and-scan" strategy-a therapeutic
approach.
PMID- 28421259
TI - [Bariatric surgery versus medical therapy in the treatment of obesity].
PMID- 28421260
TI - [Gigantic exophytically growing tumor of the occipital scalp : A complex
diagnostic and reconstructive challenge].
PMID- 28421261
TI - [Positive and negative predictors of long-term results after an osteotomy around
the knee joint].
AB - A frequently asked question in the context of any surgical procedure, including
an osteotomy around the knee joint, is "which parameters are in favor of a
therapeutic success in this special case?" If the analysis of the leg geometry is
in favor of an osteotomy, then the patient must be assessed further, taking into
account the joint status and patient's condition. Positive outcome predictors for
long-term success of an osteotomy around the knee, especially for a valgus
osteotomy at the tibia are a tibial bone varus angle (TBVA) > 3-5 degrees , knee
joint range of motion > 100 degrees flexion, male sex, and a BMI < 30. It is
unclear whether the degree of degeneration of the affected (medial) compartment
is of special relevance. The severity of malalignment, the patient's sex, and
psychopathological comorbidities are not important.
PMID- 28421262
TI - Transanal Endoscopic Operation Versus Conventional Transanal Excision for Rectal
Tumors: Case-Matched Study with Propensity Score Matching.
AB - BACKGROUNDS: Although transanal endoscopic surgery is practiced worldwide, there
is no consensus on comparative outcomes between transanal endoscopic operation
(TEO) and transanal excision (TAE). In this study, we reviewed our experiences
with these techniques and compared patients who underwent TEO and TAE using
propensity score matching (PSM). METHODS: A total of 207 patients underwent local
rectal tumor excision between January 2008 and November 2015. To overcome
selection bias, we used PSM to achieve a one-to-one TEO: TAE ratio. We included
baseline characteristics, age, sex, surgeon, American Society of
Anesthesiologists score, tumor location (clockwise direction), involved
circumference quadrants, tumor size, and pathology. RESULTS: After PSM, 72
patients were included in each group. The tumor distance from the anal verge was
higher in the TEO group (8.0 [5-10] vs. TAE: 4.0 [3-5], p < 0.001). Complication
rates did not differ between the groups (TEO: 8.3% vs. TAE: 11.1%, p = 0.39). TEO
was associated with a shorter hospital stay (3.01 vs. 4.68 days, p = 0.001),
higher negative margin rate (95.8 vs. 86.1%, p = 0.039), and non-fragmented
specimen rate vs. TAE (98.6 vs. 90.3%, p = 0.029). CONCLUSIONS: TEO was more
beneficial for patients with higher rectal tumors. Regardless of tumor location,
involved circumference quadrants, and tumor size, TEO may more effectively
achieve negative resection margins and non-fragmented specimens. Consequently,
although local excision method according to tumor distance may be important, TEO
will become the standard for rectal tumors.
PMID- 28421263
TI - Bone Mineral Density and Fracture Risk in Ankylosing Spondylitis: A Meta
Analysis.
AB - We conducted a meta-analysis of studies to examine the risk of vertebral and non
vertebral fractures in patients with ankylosing spondylitis (AS). Additionally,
we evaluated the risk factors of vertebral fractures in AS. Two authors
independently searched Embase and Medline for studies that had assessed the risk
of fractures in patients with AS. Twenty-two studies were eligible for the meta
analysis. Patients with AS had high frequency of vertebral fractures [OR (95%
CI): 1.96 (1.52-2.51)]. Major risk factors for vertebral fractures in patients
with AS include low BMD at the femoral neck and total hip, male gender, longer
disease duration, higher BASDAI, higher BASRI, and possibly inflammatory bowel
disease. The risk of non-vertebral fractures [OR (95% CI) 1.10 (1.04-1.15)] was
10% higher in AS patients than in controls. The risk of hip fractures in AS
patients was not statistically significant [OR (95% CI) 1.17 (0.71-1.92)] in our
pooled analysis. We found that patients with AS are at high risk of vertebral
fractures. Male sex, duration of AS, mSASSS, BASRI, and low BMD at the hip and
distal forearm were associated with the risk of vertebral fractures. Current
evidence on the risk of hip fractures in patients with AS is inconsistent. Data
about the effect of NSAIDs and TNF inhibitors on fracture risk in AS are limited.
PMID- 28421266
TI - Reactive oxygen species mediated T lymphocyte abnormalities in an iron-overloaded
mouse model and iron-overloaded patients with myelodysplastic syndromes.
AB - The adverse effects of iron overload have raised more concerns as a growing
number of studies reported its association with immune disorders. This study
aimed to investigate alterations in the immune system by iron overload in
patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model.
The peripheral blood from patients was harvested to test the effect of iron
overload on the subsets of T lymphocytes, and the level of reactive oxygen
species (ROS) was also evaluated. The data showed that iron-overloaded patients
had a lower percentage of CD3+ T cells and disrupted T cell subsets, concomitant
with higher ROS level in lymphocytes. In order to explore the mechanism, male
C57Bl/6 mice were intraperitoneally injected with iron dextran at a dose of 250
mg/kg every 3 days for 4 weeks to establish an iron-overloaded mouse model and
the blood of each mouse was collected for the analysis of the T lymphocyte
subsets and T cell apoptosis. The results showed that iron overload could reduce
the percentage of CD3+ T cells and the ratio of Th1/Th2 and Tc1/Tc2 but increase
the percentage of regulatory T (Treg) cells and the ratio of CD4/CD8. We also
found that iron overload induced the apoptosis of T lymphocytes and increased its
ROS level. Furthermore, these effects could be partially recovered after treating
with antioxidant N-acetyl-L-cysteine (NAC) or iron chelator deferasirox (DFX).
Taken together, these observations indicated that iron overload could selectively
affect peripheral T lymphocytes and induce an impaired cellular immunity by
increasing ROS level.
PMID- 28421267
TI - Potential Distribution of Mountain Cloud Forest in Michoacan, Mexico:
Prioritization for Conservation in the Context of Landscape Connectivity.
AB - Landscape connectivity is essential in biodiversity conservation because of its
ability to reduce the effect of habitat fragmentation; furthermore is a key
property in adapting to climate change. Potential distribution models and
landscape connectivity studies have increased with regard to their utility to
prioritizing areas for conservation. The objective of this study was to model the
potential distribution of Mountain cloud forests in the Transversal Volcanic
System, Michoacan and to analyze the role of these areas in maintaining landscape
connectivity. Potential distribution was modeled for the Mountain cloud forests
based on the maximum entropy approach using 95 occurrence points and 17
ecological variables at 30 m spatial resolution. Potential connectivity was then
evaluated by using a probability of connectivity index based on graph theory. The
percentage of variation (dPCk) was used to identify the individual contribution
of each potential area of Mountain cloud forests in overall connectivity. The
different ways in which the potential areas of Mountain cloud forests can
contribute to connectivity were evaluated by using the three fractions derived
from dPCk (dPCintrak, dPCfluxk, and dPCconnectork). We determined that 37,567 ha
of the TVSMich are optimal for the presence of Mountain cloud forests. The
contribution of said area in the maintenance of connectivity was low. The
conservation of Mountain cloud forests is indispensable, however, in providing or
receiving dispersal flows through TVSMich because of its role as a connector
element between another habitat types. The knowledge of the potential capacity of
Mountain cloud forests to promote structural and functional landscape
connectivity is key in the prioritization of conservation areas.
PMID- 28421264
TI - Epidemiology of Sarcopenia: Determinants Throughout the Lifecourse.
AB - Sarcopenia is an age-related syndrome characterised by progressive and
generalised loss of skeletal muscle mass and strength; it is a major contributor
to the risk of physical frailty, functional impairment in older people, poor
health-related quality of life and premature death. Many different definitions
have been used to describe sarcopenia and have resulted in varying estimates of
prevalence of the condition. The most recent attempts of definitions have tried
to integrate information on muscle mass, strength and physical function and
provide a definition that is useful in both research and clinical settings. This
review focuses on the epidemiology of the three distinct physiological components
of sarcopenia, and highlights the similarities and differences between their
patterns of variation with age, gender, geography and time and the individual
risk factors that cluster selectively with muscle mass, strength and physical
function. Methods used to measure muscle mass, strength and physical functioning
and how differences in these approaches can contribute to the varying prevalence
rates will also be described. The evidence for this review was gathered by
undertaking a systematic search of the literature. The descriptive
characteristics of muscle mass, strength and function described in this review
point to the urgent need for a consensual definition of sarcopenia incorporating
these parameters.
PMID- 28421268
TI - Using a Population Model to Inform the Management of River Flows and Invasive
Carp (Cyprinus carpio).
AB - Carp are a highly successful invasive fish species, now widespread, abundant and
considered a pest in south-eastern Australia. To date, most management effort has
been directed at reducing abundances of adult fish, with little consideration of
population growth through reproduction. Environmental water allocations are now
an important option for the rehabilitation of aquatic ecosystems, particularly in
the Murray-Darling Basin. As carp respond to flows, there is concern that
environmental watering may cause floodplain inundation and provide access to
spawning habitats subsequently causing unwanted population increase. This is a
management conundrum that needs to be carefully considered within the context of
contemporary river flow management (natural, environmental, irrigation). This
paper uses a population model to investigate flow-related carp population
dynamics for three case studies in the Murray-Darling Basin: (1) river and
terminal lakes; (2) wetlands and floodplain lakes; and (3) complex river channel
and floodplain system. Results highlight distinctive outcomes depending on site
characteristics. In particular, the terminal lakes maintain a significant source
carp population regardless of river flow; hence any additional within-channel
environmental flows are likely to have little impact on carp populations. In
contrast, large-scale removal of carp from the lakes may be beneficial,
especially in times of extended low river flows. Case studies 2 and 3 show how
wetlands, floodplain lakes and the floodplain itself can now often be inundated
for several months over the carp spawning season by high volume flows provided
for irrigation or water transfers. Such inundations can be a major driver of carp
populations, compared to within channel flows that have relatively little
effecton recruitment. The use of a population model that incorporates river flows
and different habitats for this flow-responsive species, allows for the
comparison of likely population outcomes for differing hydrological scenarios to
improve the management of risks relating to carp reproduction and flows.
PMID- 28421269
TI - Thermal balance of Nellore cattle.
AB - This work aimed at characterizing the thermal balance of Nellore cattle from the
system of indirect calorimetry using a facial mask. The study was conducted at
the Animal Biometeorology Laboratory of the Sao Paulo State University,
Jaboticabal, Brazil. Five male Nellore weighing 750 +/- 62 kg, at similar ages
and body conditions were distributed in four 5 * 5 Latin squares (5 days of
records and five schedules) during 20 days. Physiological and environmental
measurements were obtained from the indirect calorimetry system using a facial
mask. Respiratory parameters, hair coat, skin, and rectal temperature were
continuously recorded. From this, metabolic heat production, sensible and latent
ways of heat transfer were calculated. Metabolic heat production had an average
value of 146.7 +/- 0.49 W m-2 and did not change (P > 0.05) over the range of air
temperature (24 to 35 degrees C). Sensible heat flow reached 60.08 +/- 0.81 W m
2 when air temperature ranged from 24 to 25 degrees C, being negligible in
conditions of temperature above 33 degrees C. Most of the heat produced by
metabolism was dissipated by cutaneous evaporation when air temperature was
greater than 30 degrees C. Respiratory parameters like respiratory rate and
ventilation remained stable (P > 0.05) in the range of temperature studied. Under
shade conditions and air temperature range from 24 to 35 degrees C, metabolic
heat production, respiratory rate, and ventilation of mature Nellore cattle
remain stable, which is indicative of low energetic cost to the thermoregulation.
PMID- 28421270
TI - Climate variability impacts on rainfed cereal yields in west and northwest Iran.
AB - In order to assess the response of wheat and barley to climate variability, the
correlation between variations of yields with local and global climate variables
was investigated in west and northwest Iran over 1982-2013. The global climate
variables were the El Nino-Southern Oscillation (ENSO), Arctic Oscillation (AO),
and North Atlantic Oscillation (NAO) signals. Further, minimum (T min), maximum
(T max), and mean (T mean) temperature, diurnal temperature range (DTR),
precipitation, and reference evapotranspiration (ET0) was used as local weather
factors. Pearson's correlation coefficient was applied to analyze the
relationships between climatic variables and yields. Unlike T min, T mean, ET0,
and T max, the yields were significantly associated with the entire growing
season (EGS) DTR in most sites. Therefore, considering weather extreme variables
such as DTR sheds light on the crop-temperature interactions. It is also found
that the April-May-June (AMJ), October-November-December (OND), and EGS rainfall
variations markedly influence the yields. Unlike the AO and NAO indices, the Nino
4 and SOI (the ENSO-related signals) were significantly correlated with the OND
and EGS precipitation and DTR. Thus, the ENSO anomalies highly impact rainfed
yields through influencing the OND and EGS rainfall and DTR in the studied sites.
As the correlation coefficient of the OND and July-August-September (JAS) Nino-4
with yields was significant (p < 0.05) for almost all locations, the JAS and OND
Nino-4 may be a good proxy for cereal yield forecasting. Further, an
insignificant increment and a significant reduction in yields are expected in La
Nina and El Nino years, respectively, relative to neutral years.
PMID- 28421271
TI - [Hereditary bone tumors].
AB - Hereditary bone tumors are rare and result from mutations affecting cell cycle
regulation (e.g. retinoblastoma syndrome/RB1 and Li-Fraumeni syndrome/TP53,
Gardner syndrome/APC), energy metabolism (enchondromatosis/IDH1/2), complex
signaling cascades (multiple hereditary exostoses/EXT1/2) and DNA integrity
(Rothmund-Thomson/RECQL4, Werner/WRN and Bloom syndromes/BLM). The majority of
syndromes are incompletely understood and can lead to multiple benign tumors, of
which some might undergo secondary malignant transformation over time
(enchondromatosis: enchondromas, multiple hereditary exostoses: osteochondromas,
Gardner syndrome: osteomas) or bone sarcomas, primarily osteosarcomas as primary
(Li-Fraumeni, Rothmund-Thomson, Werner and Bloom syndromes) or secondary
manifestation (retinoblastoma syndrome) of the disease. Some syndromes
additionally predispose to the development of a variety of other malignant tumors
during life. Compared to sporadically occurring tumors, syndrome-related
neoplasms can differ in the time of manifestation, site and histology, which can
help in recognizing a specific tumor predisposition syndrome.
PMID- 28421272
TI - [The pathology of adverse events with immune checkpoint inhibitors].
AB - BACKGROUND: Immunotherapy has gained importance with the development of new
effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal
antibodies that promote T-cell mediated tumor immune rejection. Checkpoint
blockade also carries the risk of inducing autoimmune reactions ("immune related
adverse events", irAEs). The diagnosis and classification of irAEs constitute a
new and important field in pathology. AIM: Practice-oriented review of the
diagnosis and classification of irAEs. MATERIALS AND METHODS: Structured,
selective literature review based on PubMed und UpToDate (r) online. RESULTS: The
most common irAEs affect the skin, the gastrointestinal tract, the liver, and the
respiratory system. The correct diagnosis and classification of irAEs by an
interdisciplinary care team is essential for appropriate therapy and the
prevention of long-term sequelae. Other important irAEs affect the endocrine
organs, the heart, the joints, the kidneys and the nervous system. Because of
their rarity and/or limited options for bioptic diagnosis, only limited data on
the morphology and pathophysiology of these irAEs are currently available.
Autopsies carried out after ICI therapy constitute an important element of
quality control and allow better documentation of the incidence and pathogenesis
of irAEs. DISCUSSION: Pathology plays a central role in the diagnosis and
treatment of irAEs. Future studies may contribute to a better mechanistic
understanding of irAEs for individualized knowledge-based risk assessment.
PMID- 28421273
TI - [Definition, classification, clinical diagnosis and prognosis of fibromyalgia
syndrome : Updated guidelines 2017 and overview of systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
systematic search of the literature from December 2010 to May 2016 was performed
in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of
evidence were assigned according to the classification system of the Oxford
Centre for Evidence-Based Medicine version 2009. The strength of recommendations
was achieved by multiple step formalized procedures to reach a consensus. The
guidelines were reviewed and approved by the board of directors of the societies
engaged in the development of the guidelines. RESULTS AND CONCLUSION: The
clinical diagnosis of fibromyalgia syndrome can be established by the American
College of Rheumatology (ACR) 1990 classification criteria (with examination of
tender points) or without the examination of tender points by the modified
preliminary diagnostic ACR 2010 or 2011 criteria.
PMID- 28421274
TI - Endometrioid endometrial adenocarcinoma: an increase of G3 cancers?
AB - PURPOSE: Endometrial cancer can be divided into two types: endometrioid Type 1
(G1, G2) has a hormonal driven etiology, while Type 2 is more aggressive (G3
endometrioid, clear cell and serous cancer type) and estrogen independent. We
noticed an increase of more aggressive G3 endometrioid endometrial
adenocarcinomas. This observation is of relevance for daily clinical practice
because therapy depends on the histopathological grading and myometrial invasion.
G3 cancers or myometrial invasion of more than 50% should be hysterectomized
including bilateral adnexectomy with pelvine and paraaortal lymphadenectomy. In
G1/G2 and lower infiltration levels, hysterectomy with adnexectomy without
lymphadenectomy is sufficient. METHODS: Data of the ASF Statistic were used to
analyze the changes in the incidences of patients with endometrioid cancer,
grading groups and their first diagnosed stages between 2006 and 2014. RESULTS:
2611 patients, with 243-341 women per year, were analyzed. The number of
diagnosed G1 tumors increased from 25 to 37% and the G3 tumors from 18 to 32%,
whereas the G2 cancers decreased from 58 to 31%. Despite the rise of G3 tumors,
an increase in age at diagnosis was not observed. The proportions of initial
diagnosed stages (FIGO I-IV) in each grading remained constant over time.
CONCLUSION: Potential consequences in treatment recommendations and prognosis
urge attention to the detected increase of G3 endometrioid cancers.
PMID- 28421275
TI - No association between hand and foot temperature responses during local cold
stress and rewarming.
AB - PURPOSE: The purpose was to examine whether associations exist between
temperature responses in the fingers vs. toes and hand vs. foot during local cold
water immersion and rewarming phases. METHODS: Seventy healthy subjects (58
males, 12 females) immersed their right hand or right foot, respectively, in 8
degrees C water for 30 min (CWI phase), followed by a 15-min spontaneous
rewarming (RW) in 25 degrees C air temperature. RESULTS: Temperature was lower
in the toes than the fingers during the baseline phase (27.8 +/- 3.0 vs. 33.9 +/-
2.5 degrees C, p < 0.001), parts of the CWI phase (min 20-30: 8.8 +/- 0.7 vs.
9.7 +/- 1.4 degrees C, p < 0.001), and during the RW phase (peak temperature:
22.5 +/- 5.1 vs. 32.7 +/- 3.6 degrees C, p < 0.001). Cold-induced vasodilatation
(CIVD) was more common in the fingers than in the toes (p < 0.001). Within the
first 10 min of CWI, 61% of the subjects exhibited a CIVD response in the
fingers, while only 6% of the subjects had a CIVD response in the toes. There was
a large variability of temperature responses both within and between extremities,
and there was a weak correlation between finger- and toe temperature both during
the CWI (r = 0.21, p = 0.08) and the RW phases (r = 0.26, p = 0.03). CONCLUSIONS:
Results suggest that there is generally a lower temperature in the toes than the
fingers after a short time of local cold exposure and that the thermal responses
of the fingers/hands are not readily transferable to the toes/foot.
PMID- 28421276
TI - Erratum to: The laminar organization of the motor cortex in monodactylous
mammals: a comparative assessment based on horse, chimpanzee, and macaque.
PMID- 28421277
TI - Author's reply to a letter-to-the-editor about the paper 'Eardrum thickening
approach for the treatment of patulous Eustachian tube'.
PMID- 28421278
TI - An efficient method to enrich for knock-out and knock-in cellular clones using
the CRISPR/Cas9 system.
AB - Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9
nuclease (CRISPR/Cas9) and Transcription Activator-Like Effector Nucleases
(TALENs) are versatile tools for genome editing. Here we report a method to
increase the frequency of Cas9-targeted cellular clones. Our method is based on a
chimeric construct with a Blasticidin S Resistance gene (bsr) placed out-of-frame
by a surrogate target sequence. End joining of the CRISPR/Cas9-induced double
strand break on the surrogate target can place the bsr in frame, thus providing
temporary resistance to Blasticidin S: this is used to enrich for cells where
Cas9 is active. By this approach, in a real experimental setting, we disrupted
the Aicda gene in ~70% of clones from CH12F3 lymphoma cells (>40% biallelically).
With the same approach we knocked in a single nucleotide to reconstruct the frame
of Aicda in these null cells, restoring the function in ~37% of the clones (less
than 10% by the standard approach). Targeting of single nucleotide changes in
other genes yielded analogous results. These results support our enrichment
method as an efficient tool in genome editing.
PMID- 28421280
TI - Systems biology of seeds: deciphering the molecular mechanisms of seed storage,
dormancy and onset of germination.
AB - Seeds are heterogeneous storage reserves with wide array of storage compounds
that include various soluble carbohydrates, starch polymer, storage proteins and
lipids. These stored reserves comprise 70% of the world's caloric intake in the
form of food and animal feed produced through sustainable agriculture, which
contributes to food and nutritional security. Seed systems biology remains an
enigmatic subject in understanding seed storage processes, maturation and pre
germinative metabolism. The reviews and research articles covered in this special
issue of Plant Cell Reports highlight recent advances made in the area of seed
biology that cover various systems biology applications such as gene regulatory
networks, metabolomics, epigenetics and the role of micro-RNA in seed
development.
PMID- 28421279
TI - Sporulation: how to survive on planet Earth (and beyond).
AB - Sporulation is a strategy widely utilized by a wide variety of organisms to adapt
to changes in their individual environmental niches and survive in time and/or
space until they encounter conditions acceptable for vegetative growth. The
spores produced by bacteria have been the subjects of extensive studies, and
several systems such as Bacillus subtilis have provided ample opportunities to
understand the molecular basis of spore biogenesis and germination. In contrast,
the spores of other microbes, such as fungi, are relatively poorly understood.
Studies of sporulation in model systems such as Saccharomyces cerevisiae and
Aspergillus nidulans have established a basis for investigating eukaryotic
spores, but very little is known at the molecular level about how spores
function. This is especially true among the spores of human fungal pathogens such
as the most common cause of fatal fungal disease, Cryptococcus neoformans. Recent
proteomic studies are helping to determine the molecular mechanisms by which
pathogenic fungal spores are formed, persist and germinate into actively growing
agents of human disease.
PMID- 28421281
TI - Hearing diversity in moths confronting a neotropical bat assemblage.
AB - The tympanal ear is an evolutionary acquisition which helps moths survive
predation from bats. The greater diversity of bats and echolocation strategies in
the Neotropics compared with temperate zones would be expected to impose
different sensory requirements on the neotropical moths. However, even given some
variability among moth assemblages, the frequencies of best hearing of moths from
different climate zones studied to date have been roughly the same: between 20
and 60 kHz. We have analyzed the auditory characteristics of tympanate moths from
Cuba, a neotropical island with high levels of bat diversity and a high incidence
of echolocation frequencies above those commonly at the upper limit of moths'
hearing sensitivity. Moths of the superfamilies Noctuoidea, Geometroidea and
Pyraloidea were examined. Audiograms were determined by non-invasively measuring
distortion-product otoacoustic emissions. We also quantified the frequency
spectrum of the echolocation sounds to which this moth community is exposed. The
hearing ranges of moths in our study showed best frequencies between 36 and 94
kHz. High sensitivity to frequencies above 50 kHz suggests that the auditory
sensitivity of moths is suited to the sounds used by sympatric echolocating bat
fauna. Biodiversity characterizes predators and prey in the Neotropics, but the
bat-moth acoustic interaction keeps spectrally matched.
PMID- 28421283
TI - Shunting of the over 80s in normal pressure hydrocephalus.
AB - BACKGROUND: Idiopathic normal pressure hydrocephalus is predominantly a disease
of the elderly. By its nature, many of those who present to clinic are in
advanced old age with multiple comorbidities. Majority of patients treated are
younger than 80 years old. We present the clinical outcomes and complication
rates of patients over the age of 80 years at the time of operation, during the
past 11 years at a single institution. METHODS: Retrospective analysis of
clinical records of all patients over the age of 80 years, who presented to our
institution between 2006 and 2016. Results were analysed for co-morbidities,
immediate and delayed complications, change in mobility/cognitive function post
shunting of hydrocephalus. RESULTS: 39 patients (24 male, 15 female) met
criteria. Mean [SD] age at the time of shunt insertion was 84 years (+/- 3.22)
(range 80-94). No patients developed immediate CSF infection or sub-dural
collection, or extended length of stay due to surgical or anaesthetic
complications. There were no peri-operative or anaesthetic complications. 4
patients required a delayed surgical revision to encourage greater CSF drainage.
3 patients went on to develop delayed subdural haematoma, 1 of which was
associated with trauma, 2 through overdrainage. 1 patient experienced poor post
operative wound healing and subsequently underwent removal of shunt. Of the 34
patient followed up, 27 patients (79.4%) improved in their mobility. (64.7%)
patients/families reported symptomatic improvement in their cognition and memory.
6 (17.7%) patients did not experience an improvement in either mobility or
cognitive function. CONCLUSIONS: Our data supports the assertion that, with
proper patient selection, shunting of the over 80s with iNPH is a safe and
effective procedure.
PMID- 28421282
TI - Associations between a Mediterranean diet pattern and inflammatory biomarkers in
European adolescents.
AB - AIM: To test whether the Mediterranean diet score and each food-subgroup is
associated with inflammatory biomarkers in European adolescents. METHODS: In 464
adolescents (13-17 years) of the European HELENA study, data were available on
body composition, inflammation markers, and food intake determined by two
computerized 24-h recalls. The Mediterranean diet score and its food-subgroups
(Vegetables, Fruits and Nuts, Pulses, Cereal and Roots, Monounsaturated/Saturated
fat ratio, Dairy, Fish, Meat and Alcohol) were evaluated. A set of inflammation
related biomarkers was measured: IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TGFbeta-1,
TNF-alpha, sVCAM-1, sICAM1, sE-selectin, white blood cells, lymphocytes, CD3,
CRP, GGT, ALT, and homocysteine. Multivariate and multiple linear regression
analyses were adjusted for age, sex, country, socioeconomic status, paternal and
maternal education, adiposity, and smoking habits. RESULTS: The Mediterranean
diet score was positively associated with CRP, and negatively with sVCAM-1. The
subgroups showed the following positive/negative associations: Vegetables with IL
10(+), CRP(+), CD3(+), ALT(+), lymphocytes(+), sE-selectin(-); Fruits and Nuts
with IL-4(-), TNF-alpha; Pulses with IL-5(+), IL-6(+), IL-2(-); Cereals and Roots
with IL-6(-), IL-10(-); Monounsaturated/Saturated-fat ratio with IL-6(+), TGFbeta
1(+), sVCAM-1(+boys, -girls), homocysteine(-); Dairy with IL-1(+), IL-5(+), IL
6(+), IL-10(+), TGFbeta-1(+), homocysteine(-); Fish with homocysteine(-); Meat
with IL-2(+), IL-10(+); Alcohol with CRP(+), lymphocytes(-). Sex differences were
found. CONCLUSION: Some specific food-inflammation associations were found,
suggesting that diet is to a certain extent already related to inflammation in
adolescents and can be used in disease prevention. Also some counterintuitive
results were found, which might be due to grouping very different foods into a
single group, besides considering that the human body may respond differently
depending on the interaction between diet, lifestyle, genetics, biochemical
individuality, age and sex.
PMID- 28421284
TI - Oropharyngeal dysphagia in secondary normal pressure hydrocephalus due to
corticobulbar tract compression: cases series and review of literature.
AB - The association and mechanism involved in swallowing disturbance and normal
pressure hydrocephalus (NPH) needs to be established. We report a case report
where a patient who showed progressive swallowing dysfunction was diagnosed with
secondary NPH. Tractography analysis showed corticobulbar tract compression by
ventricular dilation. Drainage operation led to the recovery of tract volume with
an improvement of swallowing function. We also report ten case series in which
secondary NPH was associated with a swallowing disturbance. In these cases,
dysphagia also showed improvement after shunt operation. We review the literature
regarding the corticobulbar tract and its association with swallowing disturbance
and the possible underlying pathophysiological mechanism in secondary NPH. This
report highlights that swallowing disturbance may manifest in those with
secondary NPH due to corticobulbar tract involvement. Our findings suggest that
involvement of the corticobulbar tract may be a possible cause of dysphagia in
secondary NPH that may be reversible after shunt operation.
PMID- 28421285
TI - [Erratum to: Guidelines from the DOG, RG and BVA: retinal artery occlusion :
November 2016 status].
PMID- 28421286
TI - [Listening to music in old age : Investigation of utilization and psychosocial
resources].
AB - BACKGROUND: Studies with younger participants have shown that listening to music
is used to achieve a multitude of positive effects that can be summarized by
three fundamental dimensions: self-awareness, social relatedness and regulation
of mood and arousal. For the elderly, these effects contain a high potential with
respect to alleviation of affective symptoms and enhancement of social
participation; however, it is still unclear if the elderly exhibit the same
pattern of fundamental uses of listening to music as younger persons and how they
evaluate their access to music in different housing situations. MATERIAL AND
METHODS: To answer these questions, 115 persons (aged 57-94 years) in different
housing situations were asked for their motives for listening to music and their
satisfaction with various aspects of access to music. RESULTS: The elderly showed
the same pattern of the three fundamental dimensions of the use of listening to
music as younger respondents, although specific uses were more pronounced, such
as relaxation, reminiscing, and compensation for loneliness; however, the general
intensity of the use of listening to music was lower. Older people saw deficits
in the frequency, coordination, and communication of musical arrangements in
their residential environment. CONCLUSION: Older people listen to music to obtain
specific effects in the same way as younger people do; however, the decreasing
intensity of the use of listening to music, together with the desires of the
older respondents, demonstrate a need for more musical arrangements that should
be better coordinated, communicated, and preferably personalized.
PMID- 28421288
TI - [83th Annual Meeting of the German Cardiac Society - Cardiac and Circulation
Research, April 19.- 22. 2017, Mannheim].
PMID- 28421287
TI - [Age 89 years, depression, fall with pelvic fracture, severe confusion -
serotonin syndrome : Differential diagnosis, importance of CYP450 and economic
considerations].
AB - A case study of an 89-year-old patient is reported, who was admitted to hospital
because of immobility due to pain. After the cause of the pain could initially be
clarified and treated, the further clinical course in this very old woman showed
an alarming symptom complex of agitation, confusion and cognitive deterioration,
which took on grave forms. The work-up of this case showed a typical
constellation of pain and depression in old age; however, the pharmaceutical
treatment in this case is not atypical and could lead to a severe serotonin
syndrome. The interaction, diagnostics, differential diagnosis, pharmacological,
functional, codification and economic aspects of the course of the disease are
discussed.
PMID- 28421290
TI - Pulsatile high-dose treatment with antiangiogenic tyrosine kinase inhibitors
improves clinical antitumor activity.
PMID- 28421289
TI - Adult male northern elephant seals maintain high rates of glucose production
during extended breeding fasts.
AB - Many species undergo natural fasts as part of their life histories. Extended
fasting is associated with increased beta-oxidation of fatty acids and reduced
oxidation of glucose to minimize commitment of body protein to gluconeogenesis.
However, the metabolic strategies used to sustain extended fasts simultaneous
with high rates of energy expenditure are not well understood. Studies in fasting
adult female and weanling northern elephant seals (NES) have revealed high rates
of endogenous glucose production (EGP) under constraints of high nutrient demand
for lactation or development but relatively low rates of metabolism. These
studies revealed low rates of glucose oxidation and high rates of glucose
recycling through the Cori cycle. We measured rates of glucose flux in fasting
adult male NES to assess how significantly longer fasting durations, higher
metabolic rates, and greater rates of muscular activity affect glucose kinetics.
We measured glucose turnover in 18 adult males using the clearance of [6-H3]
glucose during breeding and molting. Adult male NES maintain high rates of EGP
across extended fasts. EGP greatly exceeded estimated needs for glucose-dependent
tissues, varied directly with plasma insulin and lactate concentrations, and was
inversely related to plasma ketoacid concentrations. Together, these findings
suggest that high rates of glucose production and recycling during breeding
maintain high blood glucose levels to support glucose-dependent tissues while
minimizing production of ketoacids and commitment of protein stores to glucose
production.
PMID- 28421291
TI - Tick-borne viral encephalomyeloradiculitis complicated by severe autonomic
myenteric involvement resulting in irreversible adynamic ileus.
PMID- 28421292
TI - Phylogenetic Insight into Zika and Emerging Viruses for a Perspective on
Potential Hosts.
AB - Global viral diversity is substantial, but viruses that contribute little to the
public health burden or to agricultural damage receive minimal attention until a
seemingly unimportant virus becomes a threat. The Zika virus (ZIKV) illustrated
this, as there was limited information and awareness of the virus when it was
identified as a public health emergency in February 2016. Predicting which virus
may pose a future threat is difficult. This is in part because significant
knowledge gaps in the basic biology and ecology of an emerging virus can impede
policy development, delay decision making, and hinder public health action. We
suggest using a phylogenetic framework of pathogens and their infected host
species for insight into which animals may serve as reservoirs. For example,
examining flaviviruses closely related to ZIKV, the phylogenetic framework
indicates New World monkeys are the most likely candidates to be potential
reservoirs for ZIKV. Secondarily, mammals that are in close proximity to humans
should be considered because of the increased opportunity for pathogen exchange.
The increase in human-mediated environmental change is accelerating the
probability of another previously overlooked virus becoming a significant
concern. By investing in basic science research and organizing our knowledge into
an evolutionary framework, we will be better prepared to respond to the next
emerging infectious disease.
PMID- 28421293
TI - Failure and revision rates of proximal humeral fracture treatment with the use of
a standardized treatment algorithm at a level-1 trauma center.
AB - BACKGROUND: The aims of this study were to evaluate treatment failure and
revision rates of proximal humeral fracture (PHF) treatment with a standardized
treatment algorithm within the reality of a level-1 trauma center and to identify
predictors of subsequent surgery. MATERIALS AND METHODS: The medical database of
a level-1 trauma center was screened for all primary treatments of PHFs between
January 2009 and June 2012. Medical records and imaging were analyzed to identify
the fracture morphology, pre-existing diseases, revision surgeries and treatment
failures (conversion to another treatment). The patients were asked about
subsequent surgeries by phone. A functional outcome questionnaire was mailed to
participating patients. RESULTS: Follow-up data were available for 423 of 521
patients (312 females, 111 males). The mean age at the time of primary treatment
was 68.3 years; mean follow-up was 24.6 +/- 12.3 months. The overall rate of
mandatory re-operations was 15.6%, including a failure rate of 8.3%; another 7.6%
of patients had additional arthroscopic surgeries. Treatment with anatomic hemi
prostheses was associated with the highest re-operation rates, and lowest
outcomes. Involvement of the medial calcar region, complex fracture morphologies,
cigarette smoking and alcohol-abuse were predictors for subsequent surgery.
Patients without subsequent surgery had significantly higher functional outcome
scores than patients with additional surgery. CONCLUSIONS: With the use of a
standardized treatment algorithm no treatment modality was at significantly
higher risk for having additional surgery. Complex fracture types, involvement of
the medial calcar, cigarette-smoking and alcohol-abuse were associated with
subsequent surgeries. LEVEL OF EVIDENCE: Level IV case series.
PMID- 28421294
TI - A prospective comparison of intra-arterial chemotherapy combined with
intravesical chemotherapy and intravesical chemotherapy alone after transurethral
resection with a thulium laser in high-risk non-muscle invasive bladder cancer.
AB - : Objective To compare intra-arterial chemotherapy combined with intravesical
chemotherapy with intravesical chemotherapy alone in the treatment of high-risk
non-muscle invasive bladder cancer (HRBC) after thulium laser resection of a
bladder tumor (TmLRBT). MATERIALS AND METHODS: From January 2009 to December
2013, 283 patients with HRBC were randomly assigned to the combined group (group
A, n = 141) or intravesical chemotherapy-alone group (group B, n = 142) after
TmLRBT. Intra-arterial chemotherapy was administered after initial TmLRBT, with 3
courses at 4-week intervals. Each course consisted of cisplatin (50 mg/m2) and
epirubicin (30 mg/m2). Intravesical chemotherapy was administered in both groups,
including an immediate 50 mg of epirubicin instillation after TmLRBT and weekly
maintenance for 8 weeks, followed by monthly maintenance for 1 year. RESULTS: The
recurrence rate was 29.1% (41/141) in group A and 42.9% (61/142) in group B, with
a significant difference (p = 0.01). The progression rate was 15.6% (22/141) in
group A and 25.3% (36/142) in group B, with a significant difference (p = 0.039).
Patients with concomitant carcinoma in situ (CIS) also had a lower recurrence
rate and progression rate in group A compared to those in group B (p = 0.006 and
p = 0.03, respectively). On univariate and multivariate logistic regression
analyses, patients with low-grade histology had a higher reccurrence-free rate.
Multivariate COX analysis of tumor-related factors suggested that concomitant CIS
was the only significant prognostic factor associated with poorer recurrence-free
survival and progression-free survival. CONCLUSIONS: Intra-arterial chemotherapy
combined with intravesical chemotherapy could reduce the risk of recurrence and
progression compared to intravesical chemotherapy alone in HRBC.
PMID- 28421295
TI - Do Modic changes affect cervical sagittal alignment and motion in symptomatic
patients?
AB - PURPOSE: The cervical segmental instability often occurs simultaneously with
Modic changes (MCs). However, it is unknown whether there is a relation between
the two diseases. The aim of this study was to evaluate the relationship between
MCs and cervical segmental instability, cervical curvature and range of motion
(ROM) in the cervical spine. METHODS: A total of 464 patients with neck pain or
cervical neurologic symptoms who underwent imaging examination were analyzed
retrospectively. Based on MRI imaging cervical MCs were diagnosed, and patients
were divided into with or without MCs groups. The cervical curvature and range of
motion were measured. We compared the incidence of cervical instability, cervical
curvature and ROM between the two group patients and their relationships with MCs
were studied. Logistic regression was used to study the risk factors associated
with MCs. RESULTS: MCs were observed in 94 of 464 patients and 122 of total 2320
cervical segments and were most frequent at C5-6 segment. The incidence of the
cervical instability was significantly higher in patients with MCs than those
without MCs at cervical level C3-7. In addition, cervical curvature and ROM in
patients with MCs were less than those without MCs. Logistic regression analysis
showed that the occurrence of cervical spine instability, less cervical curvature
and ROM were risk factors for MCs. CONCLUSIONS: Patients with MCs were prone to
have cervical instability at the same cervical level and may have a higher
possibility of less cervical curvature and ROM.
PMID- 28421296
TI - Metabolite signatures of doxorubicin induced toxicity in human induced
pluripotent stem cell-derived cardiomyocytes.
AB - Drug-induced off-target cardiotoxicity, particularly following anti-cancer
therapy, is a major concern in new drug discovery and development. To ensure
patient safety and efficient pharmaceutical drug development, there is an urgent
need to develop more predictive cell model systems and distinct toxicity
signatures. In this study, we applied our previously proposed repeated exposure
toxicity methodology and performed 1H NMR spectroscopy-based extracellular
metabolic profiling in culture medium of human induced pluripotent stem cell
derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer
agent. Single exposure to DOX did not show alteration in the basal level of
extracellular metabolites while repeated exposure to DOX caused reduction in the
utilization of pyruvate and acetate, and accumulation of formate compared to
control culture medium. During drug washout, only pyruvate showed reversible
effect and restored its utilization by hiPSC-CMs. On the other hand, formate and
acetate showed irreversible effect in response to DOX exposure. DOX repeated
exposure increased release of lactate dehydrogenase (LDH) in culture medium
suggesting cytotoxicity events, while declined ATP levels in hiPSC-CMs. Our data
suggests DOX perturbed mitochondrial metabolism in hiPSC-CMs. Pyruvate, acetate
and formate can be used as metabolite signatures of DOX induced cardiotoxicity.
Moreover, the hiPSC-CMs model system coupled with metabolomics technology offers
a novel and powerful approach to strengthen cardiac safety assessment during new
drug discovery and development.
PMID- 28421297
TI - Suppression of Th1 differentiation by tryptophan supplementation in vivo.
AB - Metabolism of the essential amino acid tryptophan (trp) is a key endogenous
immunosuppressive pathway restricting inflammatory responses. Tryptophan
metabolites promote regulatory T cell (Treg) differentiation and suppress
proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that
treatment with natural and synthetic tryptophan metabolites can suppress
autoimmune neuroinflammation in preclinical animal models. Here, we tested if
oral intake of tryptophan would increase immunosuppressive tryptophan metabolites
and ameliorate autoimmune neuroinflammation as a safe approach to treat
autoimmune disorders like multiple sclerosis (MS). Without oral supplementation,
systemic kynurenine levels decrease during the initiation phase of experimental
autoimmune encephalomyelitis (EAE), a mouse model of MS, indicating systemic
activation of tryptophan metabolism. Daily oral gavage of up to 10 mg/mouse/day
was safe and increased serum kynurenine levels by more than 20-fold for more than
3 h after the gavage. While this treatment resulted in suppression of myelin
specific Th1 responses, there was no relevant impact on clinical disease
activity. These data show that oral trp supplementation at subtoxic
concentrations suppresses antigen-specific Th1 responses, but suggest that the
increase in trp metabolites is not sustained enough to impact neuroinflammation.
PMID- 28421298
TI - Dog rivalry impacts following behavior in a decision-making task involving food.
AB - Dogs learn a great deal from humans and other dogs. Previous studies of socially
influenced learning between dogs have typically used a highly trained
demonstrator dog who is unfamiliar to the observer. Because of this, it is
unknown how dynamics between familiar dogs may influence their likelihood of
learning from each other. In this study, we tested dogs living together in two
dog households on whether individual dogs' rivalry scores were associated with
performance on a local enhancement task. Specifically, we wanted to know whether
dog rivalry impacted whether an observer dog would approach a plate from which a
demonstrator dog had eaten all available food, or whether the observer dog would
approach the adjacent plate that still contained food. Dog rivalry scores were
calculated using the Canine Behavioral Assessment and Research Questionnaire and
indicated each dog's tendency to engage aggressively with the other household
dog. Low-rivalry dogs were more likely to approach the empty plate than high
rivalry dogs when the observer dog was allowed to approach the plates immediately
after the demonstrator had moved out of sight. This difference between low- and
high-rivalry dogs disappeared, however, when observer dogs had to wait 5 s before
approaching the plates. The same pattern was observed during a control condition
when a human removed the food from a plate. Compared to low-rivalry dogs, high
rivalry dogs may pay less attention to other dogs due to a low tolerance for
having other dogs in close proximity.
PMID- 28421299
TI - Compared effects of calcium and sodium polystyrene sulfonate on mineral and bone
metabolism and volume overload in pre-dialysis patients with hyperkalemia.
AB - BACKGROUND: Hyperkalemia is prevalent in end-stage renal disease patients, being
involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is
commonly used for the treatment of hyperkalemia, direct comparison of effects
between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has
not yet been studied. METHODS: In a randomized and crossover design, 20 pre
dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS
therapy for 4 weeks. RESULTS: After 4-week treatments, there was no significant
difference of changes in serum potassium (K) from the baseline (DeltaK) between
the two groups. However, SPS significantly decreased serum calcium (Ca) and
magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas
CPS reduced iPTH. DeltaiPTH was inversely correlated with DeltaCa and DeltaMg (r
= -0.53 and r = -0.50, respectively). Furthermore, sodium (Na) and atrial
natriuretic peptide (ANP) levels were significantly elevated in patients with
SPS, but not with CPS, whereas DeltaNa and DeltaANP were significantly correlated
with each other in all the patients. We also found that DeltaNa and Delta(Na to
chloride ratio) were positively correlated with DeltaHCO3-. In artificial colon
fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg,
and NH3. CONCLUSION: Compared with SPS, CPS may be safer for the treatment of
hyperkalemia in pre-dialysis patients, because it did not induce
hyperparathyroidism or volume overload.
PMID- 28421300
TI - Functional Teas from the Leaves of Arbutus unedo: Phenolic Content, Antioxidant
Activity, and Detection of Efficient Radical Scavengers.
AB - The phenolic content/composition and antioxidant activity of hot/cold infusion
and decoction from the leaves of Arbutus unedo were studied for the first time.
1,1-diphenyl-2-picrylhydrazyl (DPPH?), 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid) radical cation (ABTS?+), crocin-bleaching, copper-reducing, and
liposome accelerated oxidation assays were used for the evaluation of the
activity in vitro. In vivo, the extracts were examined for their ability to
protect S. cerevisiae cells from H2O2 induced oxidative stress. An on-line high
performance liquid chromatography-DPPH? assay was applied to identify potent
radical scavengers and comment on their contribution to the total activity. The
addition of leaves to boiling water (decoction) was the most appropriate practice
to apply since the highest phenol intake (220.2 mg gallic acid/cup served) was
obtained. Additionally, its antioxidant activity was equal or superior to that of
the other extracts. Flavonols (~51-61 mg/g dry extract) were the main phenols in
all the extracts, with quercitrin accounting for ~20% of the total phenol amount.
The on-line DPPH? method verified the high potency of the decoction and indicated
as the most active radical scavengers, two galloylquinic acid derivatives and
myricitrin, accounting for ~28-45% and ~11-13% of the total scavenging,
respectively. Present data may contribute to the future exploitation of A. unedo
leaves by the food industry for health-promoting herbal tea preparations and
dietary supplements.
PMID- 28421301
TI - Multiple sclerosis and amyotrophic lateral sclerosis: a human leukocyte antigen
challenge.
AB - Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are two different
central nervous system pathology that, according to the most accredited
hypotheses, recognize a different etiopathogenesis. The simultaneous occurrence
of MS and ALS is quite unusual. To our knowledge, only three cases have been so
far described by clinical, laboratory, and post-mortem studies. We report four
new cases of this peculiar combination that have been observed and are herein
described, included their human leukocyte antigen (HLA) profile studies. On the
basis that three out of four patients in our case series presented HLA-B*18:01A,
we may hypothesize that this antigen could play a role in developing both
diseases.
PMID- 28421302
TI - Clinical and MRI improvement in a case of progressive multifocal
leukoencephalopathy.
PMID- 28421303
TI - Erratum to: Geo-helminthiasis among migrants in Sicily: A possible focus for re
emerging neurocysticercosis in Europe.
PMID- 28421304
TI - Increased autophagic degradation contributes to the neuroprotection of hydrogen
sulfide against cerebral ischemia/reperfusion injury.
AB - Hydrogen sulfide (H2S), an endogenous gaseous signal molecule, exhibits
protective effect against ischemic injury. However, its underlying mechanism is
not fully understood. We have recently reported that exogenous H2S decreases the
accumulation of autophagic vacuoles in mouse brain with ischemia/reperfusion
(I/R) injury. To further investigate whether this H2S-induced reduction of
autophagic vacuoles is caused by the decreased autophagosome synthesis and/or the
increased autophagic degradation inautophagic flux, we performed in vitro and in
vivo studies using SH-SY5Y cells for the oxygen and glucose
deprivation/reoxygenation (OGD/R) and mice for the cerebral I/R, respectively.
NaHS (a donor of H2S) treatment significantly increased cell viability and
reduced cerebral infarct volume. NaHS treatment reduced the OGD/R-induced
elevation in LC3-II (an autophagic marker), which was completely reversed by co
treatment with an autophagic flux inhibitor bafilomycin A1 (BafA1). However, H2S
did not affect the OGD/R-induced increase of the ULK1 self-association and
decrease of the ATG13 phosphorylation, which are the critical steps for the
initiation of autophagosome formation. Cerebral I/R injury caused an increase in
LC3-II, a decrease in p62 and the accumulation of autophagosomes in the cortex
and the hippocampus, which were inhibited by NaHS treatment. This H2S-induced
decline of LC3-II in ischemic brain was reversed by BafA1. Moreover, BafA1
treatment abolished the protection of H2S on the cerebral infarction.
Collectively, the neuroprotection of exogenous H2S against ischemia/hypoxia and
reperfusion/reoxygenation injury is mediated by the enhancement of autophagic
degradation.
PMID- 28421305
TI - The utility of global longitudinal strain in the identification of prior
myocardial infarction in patients with preserved left ventricular ejection
fraction.
AB - Prior myocardial infarction (MI) is associated with increased mortality and is
prevalent in certain high risk patient groups. Electrocardiogram may be used in
diagnosis, however, sensitivity is limited, thus non-invasive imaging techniques
may improve diagnosis. We investigated whether global longitudinal strain (GLS)
and longitudinal strain parameters are reduced in patients with prior MI but
preserved left ventricular ejection fraction (LVEF). The study included 40
clinical patients with prior MI occurring >3 months previously (defined as
subendocardial hyperenhancement on late Gadolinium enhancement imaging) with LVEF
>= 55% and 40 controls matched for age and LVEF. GLS, global longitudinal strain
rate (GLSR) and early diastolic longitudinal strain rate (GLSRe) were measured
from cine imaging feature tracking analysis. Presence of wall motion abnormality
(WMA) and minimum systolic wall thickening (SWT) were calculated from cine
imaging. GLS was -17.3 +/- 3.7% in prior MI versus -19.3 +/- 1.9% in controls (p
= 0.012). GLSR was -88.0 +/- 33.7%/s in prior MI versus -103.3 +/- 26.5%/s in
controls (p = 0.005). GLSRe was 76.4 +/- 28.4%/s in prior MI versus 95.5 +/-
26.0%/s in controls (p = 0.001). GLS accurately identified prior MI [AUC 0.662
(95% CI 0.54-0.785) p = 0.012] whereas WMA [AUC 0.500 (95% CI 0.386-0.614) p =
1.0] and minimum SWT [AUC 0.609 (95% CI 0.483-0.735) p = 0.093] did not. GLS,
GLSR and GLSRe are reduced in prior MI with preserved LVEF. Normal LVEF and lack
of WMA cannot exclude prior MI. Prior MI should be considered when reduced GLS,
GLSR or GLSRe are detected by non-invasive imaging.
PMID- 28421306
TI - Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Regulate the
Disposition of Acacetin Glucuronides.
AB - PURPOSE: To determine the mechanism responsible for acacetin glucuronide
transport and the bioavailability of acacetin. METHODS: Area under the curve
(AUC), clearance (CL), half-life (T1/2) and other pharmacokinetic parameters were
determined by the pharmacokinetic model. The excretion of acacetin glucuronides
was evaluated by the mouse intestinal perfusion model and the Caco-2 cell model.
RESULTS: In pharmacokinetic studies, the bioavailability of acacetin in FVB mice
was 1.3%. Acacetin was mostly exposed as acacetin glucuronides in plasma. AUC of
acacetin-7-glucuronide (Aca-7-Glu) was 2-fold and 6-fold higher in Bcrp1 (-/-)
mice and Mrp2 (-/-) mice, respectively. AUC of acacetin-5-glucuronide (Aca-5-Glu)
was 2-fold higher in Bcrp1 (-/-) mice. In mouse intestinal perfusion, the
excretion of Aca-7-Glu was decreased by 1-fold and 2-fold in Bcrp1 (-/-) and Mrp2
(-/-) mice, respectively. In Caco-2 cells, the efflux rates of Aca-7-Glu and Aca
5-Glu were significantly decreased by breast cancer resistance protein (BCRP)
inhibitor Ko143 and multidrug resistance protein 2 (MRP2) inhibitor LTC4. The use
of these inhibitors markedly increased the intracellular acacetin glucuronide
content. CONCLUSIONS: BCRP and MRP2 regulated the in vivo disposition of acacetin
glucuronides. The coupling of glucuronidation and efflux transport was probably
the primary reason for the low bioavailability of acacetin.
PMID- 28421307
TI - An Efficient and Rapid Method to Monitor the Oxidative Degradation of Protein
Pharmaceuticals: Probing Tyrosine Oxidation with Fluorogenic Derivatization.
AB - PURPOSE: The loss of potency of protein therapeutics can be linked to the
oxidation of specific amino acid residues leading to a great variety of oxidative
modifications. The comprehensive identification of these oxidative modifications
requires high-resolution mass spectrometry analysis, which requires time and
expensive resources. Here, we propose a fluorogenic derivatization method of
oxidized Tyr and Phe yielding benzoxazole derivatives, as an orthogonal technique
for the rapid screening of protein oxidation. METHODS: Four model proteins, IgG1,
human growth hormone (hGH), insulin and bovine serum albumin (BSA) were exposed
to oxidation via peroxyl radicals and metal-catalyzed reactions and efficiently
screened by fluorogenic derivatization of Tyr and Phe oxidation products.
Complementary LC-MS analysis was done to identify the extent of methionine
oxidation in oxidized proteins. RESULTS: The Fluorogenic derivatization technique
can easily be adapted to a 96-well plate, in which several protein formulations
can be screened in short time. Representatively for hGH, we show that the
formation of benzoxazole parallels the oxidation of Met to methionine sulfoxide
which enables estimation of Met oxidation by just recording the fluorescence.
CONCLUSIONS: Our rapid fluorescence based screening allows for the fast
comparison of the stability of multiple formulations.
PMID- 28421308
TI - An Intelligent Remote Monitoring System for Total Knee Arthroplasty Patients.
AB - For the first six weeks following total knee arthroplasty (TKA), a patient will
attend an outpatient clinic typically seen twice weekly. Here, an exercise regime
is performed and improvement assessed using a hand held goniometer that measures
the maximum angle of knee flexion, an important metric of progress. Additionally
a series of daily exercises is performed at home, recorded in a diary. This
protocol has problems. Patients must attend the hospital with assistance since
they are not permitted to drive for six weeks following the procedure;
appointments are sometimes missed; there are occasionally not enough
physiotherapy appointment available; furthermore, it is difficult to be sure that
patients are compliant with their exercises at home. The economic and social
costs are therefore significant both to the patient and the health service. We
describe here an automatic system that performs the monitoring of knee flexion
within a domestic environment rather than in a hospital setting. It comprises a
master and slave sensor unit that attach using Velcro straps to the thigh and
shin above and below the operation wound. The patient performs the prescribed
knee exercises whilst wearing the device, during which time it measures and
records the angles of knee flexion. The device utilises the Global System for
Mobile Communications (GSM) infrastructure to transmit data through the Internet
to a secure hospital-based server using an on-board GSM modem. The clinician is
then able to view and interpret the information from any computer with internet
access and the software. The system does not require the patient to possess a
mobile telephone, a computer, or have internet access; the necessary
communications technology is completely integrated into the device.
PMID- 28421309
TI - Genetic makeup of Shiga toxin-producing Escherichia coli in relation to clinical
symptoms and duration of shedding: a microarray analysis of isolates from Swedish
children.
AB - Shiga toxin (Stx)-producing Escherichia coli (STECs) cause non-bloody diarrhea,
hemorrhagic colitis, and hemolytic uremic syndrome, and are the primary cause of
acute renal failure in children worldwide. This study investigated the
correlation of genetic makeup of STEC strains as revealed by DNA microarray to
clinical symptoms and the duration of STEC shedding. All STEC isolated (n = 96)
from patients <10 years of age in Jonkoping County, Sweden from 2003 to 2015 were
included. Isolates were characterized by DNA microarray, including almost 280
genes. Clinical data were collected through a questionnaire and by reviewing
medical records. Of the 96 virulence genes (including stx) in the microarray, 62
genes were present in at least one isolate. Statistically significant differences
in prevalence were observed for 21 genes when comparing patients with bloody
diarrhea (BD) and with non-bloody stool (18 of 21 associated with BD). Most genes
encode toxins (e.g., stx2 alleles, astA, toxB), adhesion factors (i.e. espB_O157,
tir, eae), or secretion factors (e.g., espA, espF, espJ, etpD, nleA, nleB, nleC,
tccP). Seven genes were associated with prolonged stx shedding; the presence of
three genes (lpfA, senB, and stx1) and the absence of four genes (espB_O157,
espF, astA, and intI1). We found STEC genes that might predict severe disease
outcome already at diagnosis. This can be used to develop diagnostic tools for
risk assessment of disease outcome. Furthermore, genes associated with the
duration of stx shedding were detected, enabling a possible better prediction of
length of STEC carriage after infection.
PMID- 28421310
TI - Comparison of Selected Protein Levels in Tumour and Surgical Margin in a Group of
Patients with Oral Cavity Cancer.
AB - Oral cavity cancer belongs to head-and-neck squamous cell carcinoma group. The
purpose of the study was to assess the levels of certain proteins in a tumour and
surgical margin in a group of patients with oral cavity cancer. The levels of
DAPK1, MGMT, CDH1, SFRP1, SFRP2, RORA, TIMP3, p16, APC and RASSF1 proteins were
measured by ELISA in tissue homogenates. The protein levels of DAPK1, MGMT, CDH1,
SFRP2 and RASSF1 were significantly higher in tumour tissue than in the margin,
contrary to TIMP3 which was lower in the tumour itself. DAPK1 level in the tumour
was significantly higher in females than in males, the MGMT and p16 levels were
lower in the tumours with lymph node metastasis (N1 + N2) than in N0 samples. The
CDH1 expression was higher in a group with smoking habits, whereas TIMP3 was
lower in this group. Changes in the levels of proteins in tumour and surgical
margin may be either reflective of tumour occurrence and development, or they
might be also responsible for the progress and reoccurrence of the disease.
Levels of the studied proteins might be good prognostic factors; however, further
studies are required.
PMID- 28421311
TI - Long-term soil alteration in historical charcoal hearths affects Tuber
melanosporum mycorrhizal development and environmental conditions for fruiting.
AB - Abandoned charcoal hearths constitute a very particular habitat for spontaneous
fruiting of Tuber melanosporum, leading some harvesters to hypothesise that the
fungus could benefit from the alterations that these soils underwent. However,
ecological mechanisms involved in this relation are not fully elucidated yet. As
a first step to understand it, the influence of long-term soil alteration on the
symbiotic stage of T. melanosporum and on selected soil properties considered key
to fruiting was assessed by conducting a greenhouse bioassay and a field
observational study. In the bioassay, percent root colonisation and relative
abundance of T. melanosporum were significantly lower in hearth than in control
soils. Hearth soils showed significantly lower resistance to penetration, larger
temperature fluctuation, reduced plant cover and reduced herbaceous root
abundance. The results do not support the hypothesis that soil from historical
charcoal hearths currently enhances development of T. melanosporum mycorrhizas.
However, whether this is due to increased infectivity of native ectomycorrhizal
communities or to worse conditions for development of T. melanosporum mycorrhizas
remains unresolved. Native ectomycorrhizal communities in hearths showed altered
composition, although not a clear change in infectivity or richness. Direction of
change in hearth soil properties is compared to alteration occurring in soils
spontaneously producing T. melanosporum. The interest of these changes to improve
T. melanosporum fruiting in plantations is discussed.
PMID- 28421312
TI - An annotated translation of Noel Bernard's 1899 article 'On the germination of
Neottia nidus-avis'.
AB - We translate Noel Bernard's discovery of orchid symbiotic germination discovered
on Neottia nidus-avis, as published in the May 1899 issue of the Comptes rendus
hebdomadaires des seances de l'Academie des sciences. In his note, Bernard (1874
1911) establishes the need for a fungus, which is also forming mycorrhizae in
adults, for seeds germination. We provide illustrations reproduced from his later
works, and summaries of the French text he cited. In our annotations, we show how
early this discovery was done in Bernard's career, and insist on the scientific
framework at the end of the nineteenth century, where orchid germination was
mysterious and the need for vicinity of parents was not fully understood. We
comment the text of Bernard on the basis of the most recent knowledge on Neottia
nidus-avis and on orchid mycorrhizal fungi. Introducing his following papers, we
finally discuss the emergence of the concept of peloton digestion, and how
Bernard's work quickly paved the way to a general understanding of
mycoheterotrophic germination in orchids and beyond.
PMID- 28421313
TI - Association between forkhead-box P2 gene polymorphism and clinical symptoms in
chronic schizophrenia in a Chinese population.
AB - The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in
the susceptibility to schizophrenia; however, few studies have investigated the
association between FOXP2 gene polymorphism and clinical symptoms in
schizophrenia. This study investigated whether the FOXP2 gene was associated with
the development and symptoms of schizophrenia in relatively genetically
homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped
in 1069 schizophrenia inpatients and 410 healthy controls using a case-control
design. The patients' psychopathology was assessed by the Positive and Negative
Syndrome Scale (PANSS). We found no significant differences in the genotype and
allele distributions between the patient and control groups. Interestingly, we
found significant differences in PANSS total, positive symptom, and general
psychopathology scores between genotypic subgroups in patients, with the higher
score in patients with CC genotype than those with CT genotype (all p < 0.05).
After adjusting demographic and clinical variables, the difference still remained
significant for the PANSS positive symptom score and general psychopathology
(both p < 0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may
not contribute to the development of schizophrenia, but may contribute to the
clinical symptoms of schizophrenia among Han Chinese.
PMID- 28421314
TI - The impact of body mass index on the risk of high spinal block in parturients
undergoing cesarean delivery: a retrospective cohort study.
AB - PURPOSE: To investigate the hypothesis that the risk of high spinal block is not
increased in obese parturients undergoing cesarean delivery compared to non-obese
parturients. METHODS: This is a retrospective study at an academic center. We
searched the perioperative database for women who underwent cesarean delivery
under spinal or combined spinal epidural anesthesia with hyperbaric bupivacaine
>=10.5 mg. A body mass index (BMI) >=30 kg/m2 was defined as obese. We
categorized obesity into: obesity class I (BMI = 30-34.9 kg/m2), obesity class II
(BMI = 35-39.9 kg/m2), obesity class III (BMI = 40-49.9 kg/m2), and super obese
(BMI >=50 kg/m2). The primary outcome was high spinal block defined as need to
convert to general anesthesia within 20 min of spinal placement as a result of
altered mental status, weakness, or respiratory distress resulting from the high
block, or a recorded block height >=T1. RESULTS: The analysis included 5015
women. High spinal blocks occurred in 29 patients (0.6%). The risk of high spinal
was significantly different according to BMI (p = 0.025). In a multivariate
model, BMI (p = 0.008) and cesarean delivery priority (p = 0.009) were associated
with high blocks. BMI >=50 kg/m2 was associated with greater odds of high block
compared to BMI <30 kg/m2 [odds ratio (95% confidence interval): 6.3 (2.2,
18.5)]. Scheduled cesarean delivery was also associated with greater odds of high
block compared with unscheduled delivery. CONCLUSIONS: At standard spinal doses
of hyperbaric bupivacaine used in our practice (>=10.5 mg), there were greater
odds of high block in those with BMI >=50 kg/m2.
PMID- 28421315
TI - In Reply: Similarities between parasternal intercostal nerve block and
subpectoral interfascial plane block.
PMID- 28421316
TI - Comparison of the coracoid and retroclavicular approaches for ultrasound-guided
infraclavicular brachial plexus block.
AB - PURPOSE: This prospective randomized study compared the coracoid and
retroclavicular approaches to ultrasound-guided infraclavicular brachial plexus
block (IBPB) in terms of needle tip and shaft visibility and quality of block. We
hypothesized that the retroclavicular approach would increase needle tip and
shaft visibility and decrease the number of needle passes compared to the
coracoid approach. METHODS: A total of 100 adult patients who received IBPB block
for upper limb surgery were randomized into two groups: a coracoid approach group
(group C) and a retroclavicular approach group (group R). In group C, the needle
was inserted 2 cm medial and 2 cm inferior to the coracoid process and directed
from ventral to dorsal. In group R, the needle insertion point was posterior to
the clavicle and the needle was advanced from cephalad to caudal. All ultrasound
images were digitally stored for analysis. The primary aim of the present study
was to compare needle tip and shaft visibility between the coracoid approach and
retroclavicular approach in patients undergoing upper limb surgery. The secondary
aim was to investigate differences between the two groups in the number of needle
passes, sensory and motor block success rates, surgical success rate, block
performance time, block performance-related pain, patient satisfaction, use of
supplemental local anesthetic and analgesic, and complications. RESULTS: Needle
tip visibility and needle shaft visibility were significantly better in group R
(p = 0.040, p = 0.032, respectively). Block performance time and anesthesia
related time were significantly shorter in group R (p = 0.022, p = 0.038,
respectively). Number of needle passes was significantly lower in group R (p =
0.044). Paresthesia during block performance was significantly higher in group C
(p = 0.045). There were no statistically significant differences between the two
groups in terms of sensory or motor block success, surgical success, block
related pain, and patient satisfaction. CONCLUSION: The retroclavicular approach
is associated with better needle tip and shaft visibility, reduced performance
time and anesthesia-related time, less paresthesia during block performance, and
fewer needle passes than the coracoid approach. TRiAL REGISTRY NUMBER:
Clinicaltrials.gov (no. NCT02673086).
PMID- 28421317
TI - Effect of oral carbohydrate with amino acid solution on serum oxidative/anti
oxidative status in healthy volunteers.
AB - The aim of this work was to investigate the effect of oral carbohydrate with
amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in
healthy persons. Fourteen healthy volunteers were segregated into control and ONS
groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle
Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the
day of the experiment. Volunteers in the control group fasted after dinner and
drank only water until 7:00 am on the day of the experiment. In both groups,
blood was collected at 9:00 am. The serum total oxidant levels and antioxidant
capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites)
test and BAP (biological antioxidant potential) test, respectively. In the ONS
group, the serum d-ROMs level was significantly lower than in the control group
(297 +/- 43 and 327 +/- 41 U.CARR, respectively, p = 0.018), while the serum BAP
level was significantly higher than the control group (2410 +/- 432 and 1979 +/-
397 umol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much
higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that
an ONS with arginine loading could decrease oxidative stress and increase
antioxidant capacity in healthy volunteers.
PMID- 28421318
TI - Mental Health Care Use in Children of Parents with Mental Health Problems:
Results of the BELLA Study.
AB - Whether parental mental health problems facilitate or hinder the use of mental
health care of the parents' children is still unclear. The present cross
sectional study examined mental health care use and potential predictors in a
population based sample. Children of parents with mental health problems (CPM)
were nearly 5 times more likely to use mental health care compared to children of
parents without mental health problems. A multiple regression analysis revealed
that the most important predictors of mental health care use for CPM were active
family life (OR = 2.67) and children's own mental health problems (OR = 1.18 self
report, 1.17 parent-report). Additionally, parental strain showed a tendency to
predict mental health care use (OR = 2.45). This study demonstrates that parental
mental health problems are associated with mental health care use in their
children and that improving certain family factors may support children's mental
health care use.
PMID- 28421319
TI - Inferior vena cava segmentation with parameter propagation and graph cut.
AB - PURPOSE: The inferior vena cava (IVC) is one of the vital veins inside the human
body. Accurate segmentation of the IVC from contrast-enhanced CT images is of
great importance. This extraction not only helps the physician understand its
quantitative features such as blood flow and volume, but also it is helpful
during the hepatic preoperative planning. However, manual delineation of the IVC
is time-consuming and poorly reproducible. METHODS: In this paper, we propose a
novel method to segment the IVC with minimal user interaction. The proposed
method performs the segmentation block by block between user-specified beginning
and end masks. At each stage, the proposed method builds the segmentation model
based on information from image regional appearances, image boundaries, and a
prior shape. The intensity range and the prior shape for this segmentation model
are estimated based on the segmentation result from the last block, or from user-
specified beginning mask if at first stage. Then, the proposed method minimizes
the energy function and generates the segmentation result for current block using
graph cut. Finally, a backward tracking step from the end of the IVC is performed
if necessary. RESULTS: We have tested our method on 20 clinical datasets and
compared our method to three other vessel extraction approaches. The evaluation
was performed using three quantitative metrics: the Dice coefficient (Dice), the
mean symmetric distance (MSD), and the Hausdorff distance (MaxD). The proposed
method has achieved a Dice of [Formula: see text], an MSD of [Formula: see text]
mm, and a MaxD of [Formula: see text] mm, respectively, in our experiments.
CONCLUSION: The proposed approach can achieve a sound performance with a
relatively low computational cost and a minimal user interaction. The proposed
algorithm has high potential to be applied for the clinical applications in the
future.
PMID- 28421320
TI - Hepatocyte-specific depletion of ubiquitin regulatory X domain containing protein
8 accelerates fibrosis in a mouse non-alcoholic steatohepatitis model.
AB - Ubiquitin regulatory X domain-containing protein 8 (UBXD8) is engaged in the
degradation of lipidated apolipoprotein B in hepatocytes. We previously showed
that hepatocyte-specific UBXD8-deficient mice (U8-HKO) fed a moderately high-fat
diet (31 kcal % fat) showed periportal macrovesicular steatosis along with a
decrease in very low-density lipoprotein secretion, but did not develop fibrosis.
In the present study, we examined whether U8-HKO mice show NASH-like phenotypes
when fed a very high-fat diet (60 kcal % fat). U8-HKO mice and their age-matched
littermates (control) were fed with two NASH model diets: choline-sufficient very
high-fat diet and choline-deficient very high-fat diet. After being fed a very
high-fat diet for 2 weeks, U8-HKO mice showed hepatic fibrosis in a significantly
wider area than in the control. Fibrosis in U8-HKO mouse liver was further
enhanced under a very high-fat diet depleted of choline (the liver surface was
lumpy). Concomitant administration of an angiotensin 2 type 1 receptor blocker
reduced the hepatic fibrosis caused by the very high-fat diet, suggesting the
existence of inflammation. Carbon tetrachloride also induced hepatic fibrosis but
the severity was comparable in the control and U8-HKO mice. In conjunction with
our previous finding, the results indicate that although UBXD8 functionality can
be largely compensated in the normal setting, it is crucial to sustain VLDL
secretion when exposed to a dietary challenge of high fat. U8-HKO mice that
develop fibrosis within 2 weeks of high-fat feeding can be used as a model to
study NAFLD/NASH disease progression.
PMID- 28421321
TI - Experimental Investigations on Fluorescence Excitation and Depletion of Carbon
Dots.
AB - Carbon dots (CDs) can be readily synthesized and utilized as attractive
fluorescent probes for a variety of applications. In this study, we have
synthesized CDs using a previously published method and characterized their photo
physical properties. The resultant CDs possess prominent photo-stability and
short emission wavelength in the violet region. Our study reveals that CDs, with
weak photo-bleaching, enable them to be employed to achieve high spatial
resolution in stimulated emission depletion (STED) microscopy. The depletion
efficiency can reach 60%. More importantly, the shorter excitation wavelength of
CDs contributes to further improvement of resolution for STED microscopy. An
excellent candidate for fluorophores, these CDs have potential to be used in
super-resolution imaging for STED microscopy.
PMID- 28421322
TI - A Colorimetric and Fluorescent Probe Based on Michael Acceptor Type
Diketopyrrolopyrrole for Cyanide Detection.
AB - A new probe 1 was synthesized by incorporating an alpha,beta-unsaturated ketone
to a diketopyrrolopyrrole fluorophore. The probe exhibited a selective and
sensitive response to cyanide against other anions. Addition of CN- aqueous
solution to 1 resulted in a rapid color change from pink to light yellow together
with a blue shift from 518 to 421 nm, while other anions did not induce any
significant color change. Furthermore, the Michael addition of cyanide to 1
elicited 98% fluorescence quenching at 608 nm, which constituted the fluorescence
signature for cyanide detection. The detection limit was 0.67 MUM using the
fluorescence spectra changes, which was far lower than the WHO guideline of 1.9
MUM. Moreover, 1-based test strips could successfully detect CN- solutions.
PMID- 28421323
TI - Gene expression, nucleotide composition and codon usage bias of genes associated
with human Y chromosome.
AB - Analysis of codon usage pattern is important to understand the genetic and
evolutionary characteristics of genomes. We have used bioinformatic approaches to
analyze the codon usage bias (CUB) of the genes located in human Y chromosome.
Codon bias index (CBI) indicated that the overall extent of codon usage bias was
low. The relative synonymous codon usage (RSCU) analysis suggested that
approximately half of the codons out of 59 synonymous codons were most frequently
used, and possessed a T or G at the third codon position. The codon usage pattern
was different in different genes as revealed from correspondence analysis (COA).
A significant correlation between effective number of codons (ENC) and various GC
contents suggests that both mutation pressure and natural selection affect the
codon usage pattern of genes located in human Y chromosome. In addition, Y-linked
genes have significant difference in GC contents at the second and third codon
positions, expression level, and codon usage pattern of some codons like the
SPANX genes in X chromosome.
PMID- 28421324
TI - Weathering the storm: how lodgepole pine trees survive mountain pine beetle
outbreaks.
AB - Recent mountain pine beetle outbreaks in western North America killed millions of
lodgepole pine trees, leaving few survivors. However, the mechanism underlying
the ability of trees to survive bark beetle outbreaks is unknown, but likely
involve phytochemicals such as monoterpenes and fatty acids that can drive beetle
aggregation and colonization on their hosts. Thus, we conducted a field survey of
beetle-resistant lodgepole pine (Pinus contorta) trees to retrospectively deduce
whether these phytochemicals underlie their survival by comparing their chemistry
to that of non-attacked trees in the same stands. We also compared beetle attack
characteristics between resistant and beetle-killed trees. Beetle-killed trees
had more beetle attacks and longer ovipositional galleries than resistant trees,
which also lacked the larval establishment found in beetle-killed trees.
Resistant trees contained high amounts of toxic and attraction-inhibitive
compounds and low amounts of pheromone-precursor and synergist compounds. During
beetle host aggregation and colonization, these compounds likely served three
critical roles in tree survival. First, low amounts of pheromone-precursor (alpha
pinene) and synergist (mycrene, terpinolene) compounds reduced or prevented
beetles from attracting conspecifics to residual trees. Second, high amounts of 4
allyanisole further inhibited beetle attraction to its pheromone. Finally, high
amounts of toxic limonene, 3-carene, 4-allyanisole, alpha-linolenic acid, and
linoleic acid inhibited beetle gallery establishment and oviposition. We conclude
that the variation of chemotypic expression of local plant populations can have
profound ecological consequences including survival during insect outbreaks.
PMID- 28421325
TI - Plant-microbial competition for nitrogen increases microbial activities and
carbon loss in invaded soils.
AB - Many invasive plant species show high rates of nutrient acquisition relative to
their competitors. Yet the mechanisms underlying this phenomenon, and its
implications for ecosystem functioning, are poorly understood, particularly in
nutrient-limited systems. Here, we test the hypothesis that an invasive plant
species (Microstegium vimineum) enhances its rate of nitrogen (N) acquisition by
outcompeting soil organic matter-degrading microbes for N, which in turn
accelerates soil N and carbon (C) cycling. We estimated plant cover as an
indicator of plant N acquisition rate and quantified plant tissue N, soil C and N
content and transformations, and extracellular enzyme activities in invaded and
uninvaded plots. Under low ambient N availability, invaded plots had 77% higher
plant cover and lower tissue C:N ratios, suggesting that invasion increased rates
of plant N acquisition. Concurrent with this pattern, we observed significantly
higher mass-specific enzyme activities in invaded plots as well as 71% higher
long-term N availability, 21% lower short-term N availability, and 16% lower
particulate organic matter N. A structural equation model showed that these
changes were interrelated and associated with 27% lower particulate organic
matter C in invaded areas. Our findings suggest that acquisition of N by this
plant species enhances microbial N demand, leading to an increased flux of N from
organic to inorganic forms and a loss of soil C. We conclude that high N
acquisition rates by invasive plants can drive changes in soil N cycling that are
linked to effects on soil C.
PMID- 28421326
TI - Nutrient enrichment in water more than in leaves affects aquatic microbial litter
processing.
AB - Nutrient enrichment of soils and water will intensify in the future and has the
potential to alter fundamental ecosystem processes, such as litter decomposition.
We tested the direct (via water nutrient enrichment) and indirect (via changes in
leaf chemistry) effects of nutrient enrichment on microbial activity and
decomposability of Quercus robur L. (oak) leaves in laboratory microcosms
simulating streams. Senescent leaves of oak trees grown without and with
fertilization were incubated under ambient and elevated water nutrient [nitrogen
(N) and phosphorus (P)] concentrations for 60 days. Soil fertilization led to an
increase in leaf (3.4*) and leaf litter (2.3*) N concentration. Increased water
dissolved nutrients concentrations stimulated microbial activity (N uptake,
microbial respiration, fungal biomass buildup and conidia production by aquatic
hyphomycetes) that translated into accelerated litter decomposition (2.1* for
unfertilized and 1.6* for fertilized trees). Leaves from fertilized trees had
higher microbial activity and decomposition rates than leaves from unfertilized
trees only at low dissolved nutrient availability. When both litter and water
nutrients concentration increased, microbial activity and leaf decomposition were
stimulated, but the effects were additive and direct effects from increased
dissolved nutrient availability were stronger than those mediated by increases in
litter N concentration (indirect effects). Our results suggest that increases in
water nutrient availability (within the range used in this study) may exert a
stronger control on microbial activity and litter decomposition than litter
nutrient enrichment.
PMID- 28421327
TI - Metal-DNA Interactions Improve signal in High-Resolution Melting of DNA for
Species Differentiation of Plasmodium Parasite.
AB - The success of high-resolution melting (HRM) analysis for distinguishing similar
DNAs with minor base mismatch differences is limited. Here, metal-mediated
structural change in DNA has been exploited to amplify HRM signals leading to
differentiation of target DNAs in an orthologous gene corresponding to four
Plasmodium species. Conserved 26-mer ssDNAs from ldh gene of the four Plasmodium
species were employed as targets. A capture probe (CP) that is fully
complementary to the Plasmodium falciparum target (FT) and has two base
mismatches each, with the targets of Plasmodium vivax (VT), Plasmodium malariae,
(MT), and Plasmodium ovale (OT), was considered. The DNA duplexes were treated
with metal ions for structural perturbation and analyzed by HRM. Distinct
resolution of melting fluorescence signal in otherwise identical HRM profiles for
each of the DNA duplexes was achieved by using Ca+2 or Mg+2 ions, where, Ca+2
conferred higher resolution. The increase in resolution for CP-FT versus CP-OT,
CP-FT versus CP-VT, CP-FT versus CP-MT, CP-VT versus CP-OT, and CP-MT versus CP
OT with Ca-DNA as compared to control was 67.3-, 20.4-, 22.0-, 10.9-, and 8.3
fold, respectively. The signal resolution was the highest at pH 8. The method
could detect 0.25 pmol/ul of the target DNA. Structural analysis showed that Ca+2
and Mg+2 ions perturbed the structure of DNA. This perturbation helped to improve
HRM signal resolution among DNA targets corresponding to the orthologous gene of
four Plasmodium species. This novel approach has potential application not only
for Plasmodium species-specific diagnosis but also for differentiation of DNAs
with minor sequence variation.
PMID- 28421328
TI - Association of adiponectin, leptin and resistin with inflammatory markers and
obesity in dementia.
AB - The aim of the study was to determine the role of adiponectin, leptin and
resistin in various types of dementia and to investigate their association with
inflammatory markers, insulin resistance and abdominal obesity. In 205 patients
with dementia [89 with Alzheimer's disease (AD), 47 with vascular dementia (VaD),
69 with mixed dementia (MD)], 113 persons with mild cognitive impairment and in
107 controls serum adiponectin, leptin and resistin levels, pro-inflammatory
[interleukin-6 (IL-6), C-reactive protein (hsCRP) and chitotriosidase] and anti
inflammatory (25-OH vitamin D, HDL-cholesterol and paraoxonase 1) markers, as
well as glucose metabolism parameters (glucose, insulin and HOMA-IR) were
determined. In all-cause dementia adiponectin and resistin levels were
significantly higher as compared to the controls; leptin levels did not show
differences. Higher adiponectin levels concerned AD and MD, whereas higher
resistin-VaD and MD. After stratification by abdominal obesity the differences in
adiponectin levels remained significant in subjects without obesity. In all-cause
dementia negative correlation of adiponectin with obesity, glucose metabolism
parameters, IL-6 and hsCRP and positive correlation with HDL-cholesterol were
found. Positive correlation of resistin with age, IL-6, hsCRP and chitotriosidase
and negative correlation with HDL-cholesterol and paraoxonase 1 were stated. We
conclude that dementia of neurodegenerative origin is characterized by elevated
adiponectin levels, whereas dementia with vascular changes by increase of
resistin. Association with inflammatory indicators may suggest the pro
inflammatory role of resistin in the development of dementia, especially in
dementia of vascular mechanism. Identification of this novel biomarker may be
important in preventing dementia.
PMID- 28421329
TI - Characterization of two TT2-type MYB transcription factors regulating
proanthocyanidin biosynthesis in tetraploid cotton, Gossypium hirsutum.
AB - MAIN CONCLUSION: Two TT2-type MYB transcription factors identified from
tetraploid cotton are involved in regulating proanthocyanidin biosynthesis,
providing new strategies for engineering condensed tannins in crops.
Proanthocyanidins (PAs), also known as condensed tannins, are important secondary
metabolites involved in stress resistance in plants, and are health supplements
that help to reduce cholesterol levels. As one of the most widely grown crops in
the world, cotton provides the majority of natural fabrics and is a supplemental
food for ruminant animals. The previous studies have suggested that PAs present
in cotton are a major contributor to fiber color. However, the biosynthesis of
PAs in cotton still remains to be elucidated. AtTT2 (transparent testa 2) is a
MYB family transcription factor from Arabidopsis that initiates the biosynthesis
of PAs by inducing the expression of multiple genes in the pathway. In this
study, we isolated two R2R3-type MYB transcription factors from Gossypium
hirsutum that are homologous to AtTT2. Expression analysis showed that both genes
were expressed at different levels in various cotton tissues, including leaf,
seed coat, and fiber. Protoplast transactivation assays revealed that these two
GhMYBs were able to activate promoters of genes encoding enzymes in the PA
biosynthesis pathway, namely anthocyanidin reductase and leucoanthocyanidin
reductase. Complementation experiments showed that both of the GhMYBs were able
to recover the transparent testa seed coat phenotype of the Arabidopsis tt2
mutant by restoring PA biosynthesis. Ectopic expression of either of the two
GhMYBs in Medicago truncatula hairy roots increased the contents of anthocyanins
and PAs compared to control lines expressing the GUS gene, and expression levels
of MtDFR, MtLAR, and MtANR were also elevated in lines expressing GhMYBs.
Together, these data provide new insights into engineering condensed tannins in
cotton.
PMID- 28421330
TI - Regulation of CONIFERALDEHYDE 5-HYDROXYLASE expression to modulate cell wall
lignin structure in rice.
AB - MAIN CONCLUSION: Regulation of a gene encoding coniferaldehyde 5-hydroxylase
leads to substantial alterations in lignin structure in rice cell walls,
identifying a promising genetic engineering target for improving grass biomass
utilization. The aromatic composition of lignin greatly affects utilization
characteristics of lignocellulosic biomass and, therefore, has been one of the
primary targets of cell wall engineering studies. Limited information is,
however, available regarding lignin modifications in monocotyledonous grasses,
despite the fact that grass lignocelluloses have a great potential for feedstocks
of biofuel production and various biorefinery applications. Here, we report that
manipulation of a gene encoding coniferaldehyde 5-hydroxylase (CAld5H, or
ferulate 5-hydroxylase, F5H) leads to substantial alterations in syringyl
(S)/guaiacyl (G) lignin aromatic composition in rice (Oryza sativa), a major
model grass and commercially important crop. Among three CAld5H genes identified
in rice, OsCAld5H1 (CYP84A5) appeared to be predominantly expressed in lignin
producing rice vegetative tissues. Down-regulation of OsCAld5H1 produced altered
lignins largely enriched in G units, whereas up-regulation of OsCAld5H1 resulted
in lignins enriched in S units, as revealed by a series of wet-chemical and NMR
structural analyses. Our data collectively demonstrate that OsCAld5H1 expression
is a major factor controlling S/G lignin composition in rice cell walls. Given
that S/G lignin composition affects various biomass properties, we contemplate
that manipulation of CAld5H gene expression represents a promising strategy to
upgrade grass biomass for biorefinery applications.
PMID- 28421331
TI - Two Troubling Trends in the Conversation Over Whether Clinical Ethics Consultants
Have Ethics Expertise.
AB - In a recent issue of the Journal of Medicine and Philosophy, several scholars
wrote on the topic of ethics expertise in clinical ethics consultation. The
articles in this issue exemplified what we consider to be two troubling trends in
the quest to articulate a unique expertise for clinical ethicists. The first
trend, exemplified in the work of Lisa Rasmussen, is an attempt to define a role
for clinical ethicists that denies they have ethics expertise. Rasmussen cites
the dependence of ethical expertise on irresolvable meta-ethical debates as the
reason for this move. We argue against this deflationary strategy because it ends
up smuggling in meta-ethical assumptions it claims to avoid. Specifically, we
critique Rasmussen's distinction between the ethical and normative features of
clinical ethics cases. The second trend, exemplified in the work of Dien Ho, also
attempts to avoid meta-ethics. However, unlike Rasmussen, Ho tries to articulate
a notion of ethics expertise that does not rely upon meta-ethics. Specifically,
we critique Ho's attempts to explain how clinical ethicists can resolve moral
disputes using what he calls the "Default Principle" and "arguments by parity."
We show that these strategies do not work unless those with the moral
disagreement already share certain meta-ethical assumptions. Ultimately, we argue
that the two trends of (1) attempting to avoid meta-ethics by denying that
clinical ethicists have ethics expertise, and (2) attempting to articulate how
ethics expertise can be used to resolve disputes without meta-ethics both fail
because they do not, in fact, avoid doing meta-ethics. We conclude that these
trends detract from what clinical ethics consultation was founded to do and ought
to still be doing-provide moral guidance, which requires ethics expertise, and
engagement with meta-ethics. To speak of ethicists without ethics expertise
leaves their role in the clinic dangerously unclear and unjustified.
PMID- 28421332
TI - The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for
Clinical Use, Content Validation, and Inter-rater Reliability.
AB - PURPOSE: The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is a
method for assessing the likelihood that a patient's muscle symptoms (e.g.,
myalgia or myopathy) were caused or worsened by statin use. The objectives of
this study were to prepare the SAMS-CI for clinical use, estimate its inter-rater
reliability, and collect feedback from physicians on its practical application.
METHODS: For content validity, we conducted structured in-depth interviews with
its original authors as well as with a panel of independent physicians.
Estimation of inter-rater reliability involved an analysis of 30 written clinical
cases which were scored by a sample of physicians. A separate group of physicians
provided feedback on the clinical use of the SAMS-CI and its potential utility in
practice. RESULTS: Qualitative interviews with providers supported the content
validity of the SAMS-CI. Feedback on the clinical use of the SAMS-CI included
several perceived benefits (such as brevity, clear wording, and simple scoring
process) and some possible concerns (workflow issues and applicability in primary
care). The inter-rater reliability of the SAMS-CI was estimated to be 0.77
(confidence interval 0.66-0.85), indicating high concordance between raters. With
additional provider feedback, a revised SAMS-CI instrument was created suitable
for further testing, both in the clinical setting and in prospective validation
studies. CONCLUSIONS: With standardized questions, vetted language, easily
interpreted scores, and demonstrated reliability, the SAMS aims to estimate the
likelihood that a patient's muscle symptoms were attributable to statins. The
SAMS-CI may support better detection of statin-associated muscle symptoms in
clinical practice, optimize treatment for patients experiencing muscle symptoms,
and provide a useful tool for further clinical research.
PMID- 28421334
TI - Guideline adherence of antidepressant treatment in outpatients with major
depressive disorder: a naturalistic study.
AB - Little is known about guideline adherence of naturalistic antidepressant drug
therapy in outpatients with major depressive disorder (MDD). The aim of the study
was to analyze guideline adherence, especially regarding treatment length,
treatment evaluation and medication change strategies. We investigated 889
patients with MDD who had been admitted for inpatient treatment and were enrolled
in the early medication change trial (ClinicalTrials.gov NCT00974155). We
investigated all patients at screening visit regarding previous outpatient drug
treatment in the index episode, which was assessed by structured interviews.
Demographic variables were obtained from patients and patients' records. 51.0% of
the patients had received previous drug treatment in the index episode, 56.6%
were females, and their mean age was 40.0 years. In the 153 patients who were
pharmacologically treated at least 8 weeks, medication was not changed in 129
(84.3%) patients. Patients who had a medication change in their index episode (n
= 24, 15.7%) waited 71.1 weeks (+/-110.4) for their treatment optimization. Only
5 of those 153 patients (3.3%) had a dose increase, whereas 132 patients (86.3%)
had no dose adaption at all. Antidepressant blood levels were measured in 46
patients (30.1%). We conclude that a large proportion of patients with MDD is not
treated in adherence to treatment guidelines recommending treatment evaluation
(e.g. therapeutic drug monitoring) and treatment change after 4 to 8 weeks in non
responders. Earlier treatment optimization may prevent long-term suffering of
patients and may avoid inpatient treatment.
PMID- 28421333
TI - Identification of putative second genetic hits in schizophrenia carriers of high
risk copy number variants and resequencing in additional samples.
AB - Copy number variants (CNVs) conferring risk of schizophrenia present incomplete
penetrance, suggesting the existence of second genetic hits. Identification of
second hits may help to find genes with rare variants of susceptibility to
schizophrenia. The aim of this work was to search for second hits of
moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the
relevant genes in additional samples. To this end, ten patients with risk CNVs at
cytobands 15q11.2, 15q11.2-13.1, 16p11.2, or 16p13.11, were subjected to whole
exome sequencing. Rare single nucleotide variants, defined as those absent from
main public databases, were classified according to bioinformatic prediction of
pathogenicity by CADD scores. The average number of rare predicted pathogenic
variants per sample was 13.6 (SD 2.01). Two genes, BFAR and SYNJ1, presented rare
predicted pathogenic variants in more than one sample. Follow-up resequencing of
these genes in 432 additional cases and 432 controls identified a significant
excess of rare predicted pathogenic variants in case samples at SYNJ1. Taking
into account its function in clathrin-mediated synaptic vesicle endocytosis at
presynaptic terminals, our results suggest an impairment of this process in
schizophrenia.
PMID- 28421335
TI - Effect of statins on hospitalization risk of bacterial infections in patients
with or without diabetes.
AB - AIMS: To investigate whether statins reduce the risk to first hospitalization of
bacterial infections, in patients with or without diabetes taking into account
prior or incident comorbidities. METHODS: By using administrative databases, the
effect of current statin use was measured on the risk of first hospitalizations
due to bacterial infections in people living in Tuscany, Italy, in the period
January 1, 2011-December 31, 2015, after excluding those with previous statins
use. Population was stratified as with (n = 128,207) or without diabetes (n =
3,304,906), and the hospitalization risk was analyzed by a Cox proportional
hazards regression analysis after adjusting for age, gender, previous
comorbidities, chronic renal failure, and prior or incident cardiovascular
diseases. RESULTS: During the 5-year follow-up, 31,543 hospitalizations for
bacterial infections were observed: 2.08(2.06-2.10) per 1000 person-year in non
diabetic and 5679: 9.13(8.94-9.32) per 1000 person-year in diabetic population.
Diabetes conferred a greater risk of hospitalizations, independently from
confounders [adjusted HR (95% CI) 2.04 (1.97-2.10); P < 0.0001]. Statin use
decreased the risk by about 2.5% for each one month of therapy, at the same
extent in subjects with or without diabetes, after adjusting for all covariates.
CONCLUSIONS: In this population, diabetes was associated by a twofold increase in
the 5-year risk of hospitalizations for bacterial infections. Statin use
decreased this risk to a same extent in subjects without or with diabetes, after
adjusting for main confounders including comorbidities, and previous or incident
cardiovascular events.
PMID- 28421336
TI - Achievement of metabolic control among children and adolescents with type 1
diabetes in Spain.
AB - AIMS: To assess metabolic control in a paediatric T1D population in Spain and
analyse the rate of severe acute decompensations and chronic complications.
METHODS: Data from patients treated at eight paediatric diabetes units with
experienced diabetes teams between June and December 2014 were analysed in an
observational prospective study. Variables included: age, sex, diabetes duration,
number of follow-up visits/year, anthropometrical data, insulin treatment
modalities, mean annual HbA1c and the prevalence of acute and chronic
complications. SPSS statistics 21.0 was used. RESULTS: A total of 853 patients
(49.7% female) with a mean age of 12.1 +/- 3.7 years were included.
Anthropometric data were normal. Mean diabetes duration was 8 +/- 3.4 years. Mean
outpatient follow-up was 4.7 +/- 0.04 visits/year. Twenty-five per cent were on
continuous subcutaneous insulin infusion (CSII). Mean HbA1c was 7.3 +/- 1% (56 +/
8 mmol/mol) and 66.6% had HbA1c < 7.5% (58 mmol/mol). HbA1c value correlated
negatively with age at onset and positively with years of diabetes, number of
visits/year and current age (F = 7.06; p = 0.01). Patients on CSII (n = 213) were
younger, attended the outpatient clinic more frequently, were diagnosed earlier,
had better metabolic control and had presented more severe hypoglycaemic episodes
the previous year. The rate of severe decompensation (episodes/100 patients/year)
was ketoacidosis 1.5 and severe hypoglycaemia 4.5. The prevalence of chronic
complications was very low. CONCLUSIONS: Our data describe the good compliance of
paediatric T1D patients treated at eight paediatric units in Spain following
international standards of metabolic control.
PMID- 28421337
TI - Glucose-independent association of adiposity and diet composition with
cardiovascular risk in children and adolescents with type 1 diabetes.
AB - AIMS: To test the hypothesis that diet composition, adiposity and glycometabolic
control could independently contribute to an increase in the cardiovascular risk
(CVR) for children/adolescents with type 1 diabetes (T1D). METHODS: One hundred
and eighty children/adolescents with T1D (age range 5-18 years) were enrolled.
Diet (3-day weighed dietary record), physical (height, weight, waist
circumference, bioelectrical impedance analysis) and biochemical (HbA1c, lipid
profile) parameters were recorded. Regression models, using non-HDL cholesterol
(a gross index of CVR) as the dependent variable and HbA1c (mmol/mol), fat mass
(FM) %, lipid-to-carbohydrate intake ratio as independent ones, were calculated.
RESULTS: Non-HDL cholesterol was significantly associated with adiposity (FM%; r
= 0.27, 95% CI 0.13-0.43), body fat distribution (waist-to-height ratio; r =
0.16, 95% CI 0.02-0.31), lipid intake [% of energy intake (EI)] (r = 0.25, 95% CI
0.11-0.41), carbohydrate intake (% EI; r = -0.24, 95% CI 0.10-0.40), lipid-to
carbohydrate intake ratio (r = 0.26, 95% CI 0.12-0.42) and blood glucose control
(HbA1c; r = 0.24, 95% CI 0.10-0.40). A p value cutoff of 0.10 was used for
covariates to be included in the regression analysis. Multiple regression
analysis showed that adiposity (FM%), blood glucose control (HbA1c) and lipid-to
carbohydrate intake ratio independently contributed to explaining the inter
individual variability of non-HDL cholesterol (R 2 = 0.163, p < 0.05).
CONCLUSIONS: Adiposity and lipid-to-carbohydrate intake ratio affect non-HDL
cholesterol, a gross index of CVR, regardless of HbA1c, in children and
adolescents with T1D. Intervention to reduce CVR in T1D patients should focus not
only on glycometabolic control but also on adiposity and diet composition.
PMID- 28421338
TI - Tailoring pharmacotherapy to specific eating behaviours in obesity: Can
recommendations for personalised therapy be made from the current data?
AB - Pharmacotherapy provides an adjunct to behaviour modification in the management
of obesity. There are a number of new drug therapies purportedly targeting
appetite; liraglutide, and bupropion/naltrexone, which are European Medicines
Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and
phentermine/topiramate, which have FDA approval only. Each of the six drugs, used
singly or in combination, has distinct pharmacological, and presumably distinct
behavioural, mechanisms of action, thus the potential to provide defined
therapeutic options to personalise the management of obesity. Yet, with regard to
pharmacotherapy for obesity, we are far from true personalised medicine. We
review the limited mechanistic data with four mono and combination
pharmacotherapies, to assess the potential for tailoring their use to target
specific obesogenic behaviours. Potential treatment options are considered, but
in the absence of adequate research in respect to effects of these drugs on
eating behaviour, neural activity and psychological substrates that underlie
poorly controlled eating, we are far from definitive therapeutic recommendations.
Specific mechanistic studies and broader behavioural phenotyping, possibly in
conjunction with pharmacogenetic research, are required to characterise
responders for distinct pharmacotherapeutic options.
PMID- 28421339
TI - Small bowel adenocarcinoma complicating Crohn's disease: a single-centre
experience emphasizing the importance of screening for dysplasia.
AB - Small bowel adenocarcinoma (SBA) complicating Crohn's disease (CD) is rare and
generally found incidentally on surgical specimens. We report our experience in
CD-associated SBA observed this last decade in a tertiary referral centre in
order to update its incidence, clinical presentation and pathological features.
All SBAs diagnosed in patients who underwent surgery for CD between 2006 and 2016
were retrospectively included. Clinico-pathological characteristics were
reviewed, and follow-up was updated. SBA was diagnosed in 9 (1.7%) of 522
patients who underwent SB resection(s) after a median CD duration of 15 years [0
32]. The median age at diagnosis was 46 years. Seven (78%) patients had
obstructive symptoms refractory to medical treatment. Pre-operative biopsy
revealed neoplasia in five (56%) patients (dysplasia in three and SBA in two)
justifying the surgery. Two (29%) of the seven patients with imaging had features
suggestive of cancer. In all specimens, SBA developed in active ileitis with
adjacent dysplasia. Stage I low-grade tubulo-glandular adenocarcinoma was
observed in 33% of patients. Stage IV high-grade adenocarcinoma was observed in
56% of patients, and mucinous/signet ring cell differentiation predominated in
44% of patients. Molecular analysis showed no BRAF mutation, a KRAS mutation in
one case and a microsatellite instability phenotype suggestive of Lynch syndrome
in one case. After a median follow-up of 24 months [7-82], four (44%) patients
died with advanced stage IV SBA. This surgical series confirms that CD-associated
SBA is rare with an incidence of 1.7%. Adjacent dysplasia was present in all
specimens and was identified before surgery in all patients who benefit from
ileal biopsies. This strengthens the importance of screening all longstanding CD
by endoscopy if surgery is not considered.
PMID- 28421340
TI - Is tumor cellularity in primary invasive breast carcinoma of prognostic
significance?
AB - Many methods of analysis to predict survival of invasive mammary carcinoma in the
post-neoadjuvant setting utilize tumor cellularity alone or in combination with
other tumor features. The goal of this study was to evaluate the prognostic value
of tumor cellularity in primary non-treated carcinoma. We used 366 cases of
invasive breast carcinoma to determine invasive tumor cellularity (%) by
reviewing a representative excisional tumor section and correlated this with
breast cancer recurrence (BCR) and overall mortality (OM). Mean patient age was
58 years (range, 21-91) and median follow-up was 87 months (range, 0.7-165). Of
the cases, 25% were Nottingham grades I, 41% grade II, and 32% grade III. The
Nottingham Prognostic Index (NPI) ranged from 2.06 to 6.8 (mean 3.93). Estrogen
receptor was positive in 66% and negative in 25% of cases. Cellularity ranged
from 2 to 99% (mean 47.6%). The OM hazard ratio increased by 1.73 for every unit
increase in NPI (P < 0.00005; 95% confidence interval 1.45-2.05) The BCR hazard
ratio increased by 2.011 for every unit increase in NPI BCR (P < 0.00005; 95%
confidence interval 1.62-2.50). Cellularity, unadjusted for other covariates, was
not significantly associated with either OM or BCR. When adjusted for NPI,
cellularity still showed no significant relation to OM or BCR. The same analysis
performed on estrogen receptor-positive and estrogen receptor-negative subgroups
continued to show no relation between cellularity and OM or BCR. In conclusion,
despite its utility in the neoadjuvant setting, we were unable to show that
cellularity is predictive of survival in primary breast carcinomas.
PMID- 28421341
TI - Insufficient activation of Akt upon reperfusion because of its novel modification
by reduced PP2A-B55alpha contributes to enlargement of infarct size by chronic
kidney disease.
AB - Chronic kidney disease (CKD) increases myocardial infarct size by an unknown
mechanism. Here we examined the hypothesis that impairment of protective PI3K
PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced
enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx
group) 4 weeks before myocardial infarction experiments, and sham-operated rats
served as controls (Sham group). Infarct size as a percentage of area at risk
after ischemia/reperfusion was significantly larger in the SNx group than in the
Sham group (56.3 +/- 4.6 vs. 41.4 +/- 2.0%). In SNx group, myocardial p-Akt
Thr308 level at baseline was elevated, and reperfusion-induced phosphorylation of
p-Akt-Ser473, p-p70s6K and p-GSK-3beta was significantly suppressed. Inhibition
of Akt-Ser473 phosphorylation upon reperfusion by Ku-0063794 significantly
increased infarct size in the Sham group but not in the SNx group. There was no
difference between the two groups in activities of mTORC2 and PDK1 and protein
level of PTEN. However, the PP2A regulatory subunit B55alpha, which specifically
targets Akt-Thr308, was reduced by 24% in the SNx group. Knockdown of B55alpha by
siRNA increased baseline p-Akt-Thr308 and blunted Akt-Ser473 phosphorylation in
response to insulin-like growth factor-1 (IGF-1) in H9c2 cells. A blunted
response of Akt-Ser473 to IGF-1 was also observed in HEK293 cells transfected
with a p-Thr308-mimetic Akt mutant (T308D). These results indicate that increased
Akt-Thr308 phosphorylation by down-regulation of B55alpha inhibits Akt-Ser473
phosphorylation upon reperfusion in CKD and that the impaired Akt activation by
insufficient Ser473 phosphorylation upon reperfusion contributes to infarct size
enlargement by CKD.
PMID- 28421342
TI - Selective retina therapy with automatic real-time feedback-controlled dosimetry
for chronic central serous chorioretinopathy in Korean patients.
AB - PURPOSE: To evaluate the safety and efficacy of selective retina therapy (SRT)
with real-time feedback-controlled dosimetry (RFD) in the treatment of chronic
central serous chorioretinopathy (CSC). METHODS: In this retrospective case
series study, 50 eyes of 49 patients with chronic CSC demonstrating focal or
diffuse foveal leakages on fundus fluorescein angiography (FFA) were included.
Following evaluation of test spots at temporal arcades, SRT (wavelength 527 nm,
pulse repetition rate 100 Hz, pulse energy ramp with maximal 15 pulses) with
retinal spot diameter of 200 MUm was applied to the areas of each leakage
observed on fluorescein angiography. Changes in mean best corrected visual acuity
(BCVA), maximum macular thickness (MMT), subretinal fluid (SRF) height, and
subfoveal choroidal thickness (SCT) were evaluated at 1, 2 and 3 months after
treatment. RFD was used for adjusting the pulse energy. Eyes received a mean of
21.1 +/- 18.1 treatment spots with a range of energies between 50uJ and 200uJ per
pulse. RESULTS: Subretinal fluid (SRF) was completely resolved in 74% (37/50
eyes) at month 3. Mean BCVA (LogMAR) was improved from 0.44 +/- 0.29 at baseline
to 0.37 +/- 0.32 at month 3 (p = 0.001). MMT was decreased from 335.0 +/- 99.8
MUm at baseline to 236.4 +/- 66.4 MUm after 3 months (p < 0.001). SRF height was
decreased from 168.0 +/- 77.3 MUm at baseline to 29.0 +/- 57.3 MUm after 3 months
(p < 0.001). However, the changes in SCT were not statistically significant (p =
0.48). CONCLUSIONS: SRT treatment with RFD showed favorable visual and anatomical
outcomes in patients with chronic CSC.
PMID- 28421343
TI - Antiplatelets and anticoagulants in vitreoretinal surgery, with a special
emphasis on novel anticoagulants: a national survey and review.
AB - PURPOSE: To survey current practice and opinion regarding the cessation of
antiplatelet and anticoagulant agents prior to vitreoretinal surgery, with
special emphasis on novel anticoagulants, and to provide an overview of current
literature. METHODS: An online survey was sent to 167 members of the British and
Eire Association of Vitreoretinal Surgeons (BEAVRS). A literature search and
analysis was conducted on studies that reviewed the bleeding risk of antiplatelet
and anticoagulant agents. RESULTS: The majority (93% for aspirin, 82% for
clopidogrel) of respondents would not suspend antiplatelet administration, and
79% would not stop warfarin before vitreoretinal surgery. Regarding the novel
anticoagulants (factor Xa inhibitors), 58% would not stop them, and 24% were
unsure. Eighty-three percent of the surgeons were not confident regarding the
management of factor Xa inhibitors preoperatively. Thirty-one percent of the
respondents felt that anticoagulation cessation was independent of the type of
vitreoretinal surgery, whereas 9% each felt that they would stop anticoagulation
if possible for diabetic vitrectomy and retinectomy. Published evidence suggests
that antiplatelet agents and warfarin do not confer a significantly greater risk
of intra- or perioperative bleeding. Evidence regarding the novel anticoagulants
is sparse. CONCLUSIONS: Further evaluation of novel anticoagulants in
vitreoretinal surgery is required in order to provide evidence-based
recommendations and address variations in practice.
PMID- 28421344
TI - Subacute cutaneous lupus erythematosus - paraneoplastic to gastric
adenocarcinoma?
PMID- 28421346
TI - Decoupling of Behavioral Trait Correlation Across Life Stages in Two
Holometabolous Insects.
AB - Many animal behaviors have a genetic base, and behavioral traits often correlate
with one another. In this study, we tested for a behavioral correlation between
tonic immobility and walking distance in the larval and adult stages
independently of two holometabolous insects. We confirmed a negative correlation
of traits between strains in adults of both the species; however, we did not find
it in larvae of either species. This suggests that the negative correlation
between tonic immobility and walking is decoupled across life stages from larva
to adult. In contrast, previous studies have reported that phenotypic
correlations between behavioral traits are maintained from larvae to adults in
hemimetabolous insects. In addition, our present results differ from previous
results with holometabolous insects. Therefore, our results suggest that
metamorphosis can change trade-offs between behavioral traits.
PMID- 28421345
TI - Long-term predictors of anxiety and depression in adult patients with asthma.
AB - BACKGROUND: It is well established that anxiety and depression are associated
with asthma, but there is limited evidence about the persistence of
anxiety/depression in asthma. The aim of our study was to assess the long-term
predictors of anxiety and depression in adult asthmatic patients. METHODS: A
total of 90 adult asthma patients (63 women, age 18-50 years) with different
levels of disease control (28 uncontrolled and 34 partially controlled) were
assessed at baseline and at follow-up after 7 years for anxiety, depression and
asthma control. The same work-up on both occasions included: demographics, living
conditions, medical history (e.g. comorbidities, adherence and exacerbations),
Hospital Anxiety and Depression Scale (HADS), Asthma Quality of Life
Questionnaire (AQLQ), disease control and lung function. Persistence was defined
as the HADS scores for anxiety and depression present at baseline and follow-up.
RESULTS: The HADS results at follow-up visit showed 36 (40%) asthma patients with
anxiety and 13 (14%) with depression, with the persistence of anxiety in 17 (19%)
and of depression in 7 (8%) patients. Significant predictors of anxiety at follow
up were HADS and AQLQ results at baseline and several parameters of asthma
control at follow-up (area under the curve AUC 0.917, 95% confidence interval CI
0.829-0.969, p < 0.001) and for depression AQLQ mood disorder domain, asthma
control and lung function (AUC 0.947, 95% CI 0.870-0.986, p < 0.001). CONCLUSION:
Anxiety and depression persist over years in some patients with asthma. The
association between mood disorders and asthma suggests potential mutual
treatability.
PMID- 28421347
TI - TU-100 exerts a protective effect against bacterial translocation by maintaining
the tight junction.
AB - PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride
(CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism
underlying this effect has not been fully elucidated. The aim of this study was
to further clarify the mechanism of CPT-11-induced bacterial translocation (BT)
and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro
by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3
groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the
CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats
were sacrificed on day 6 and their tissues were collected. RESULTS: CPT-11 and TU
100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11
treated rats developed different grades of diarrhea and BT was observed in 80% of
the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6,
TNF-alpha, IL-1beta and caspase-3 mRNAs in the large intestine. The expression of
tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was
significantly decreased in comparison to the control group. TU-100 co-treatment
significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-alpha,
IL-1beta and caspase-3, and improved the expression of occludin, claudin-4 and ZO
1. CONCLUSIONS: TU-100 can suppress the adverse effects associated with CPT-11
and improve the function of the TJ. It is possible that this occurs through the
TLR pathway.
PMID- 28421348
TI - The basal nutritional state of PDAC patients is the dominant factor for
completing adjuvant chemotherapy.
AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and several
clinical trials have shown that adjuvant chemotherapy after curative resection
can improve the prognosis of these patients. However, the adjuvant chemotherapy
completion rate is less than satisfactory. If this rate could be increased then
the overall prognosis of PDAC might be improved; however, reports addressing this
problem are insufficient. To elucidate the factors, we retrospectively
investigated PDAC patients. METHODS: Various factors of 121 PDAC patients
undergoing R0 resection, including preoperatively treated patients, were
investigated. Univariate and multivariate analyses were performed to investigate
the factors that were associated with the completion of adjuvant chemotherapy.
RESULTS: The analysis identified age and the prognostic nutritional index (PNI)
as significant independent factors. A receiver operating characteristic curve
analysis of age yielded a cutoff value of 67 years (sensitivity, 64%;
specificity, 78%). Univariate and multivariate analyses of the 61 patients who
were over 67 years of age revealed that the PNI (odds ratio, 0.85; P = 0.048) and
Evans grade (odds ratio, 0.041; P = 0.0010) were significant factors for the
completion of chemotherapy. CONCLUSIONS: The results of our investigation suggest
that nutrition should be controlled in older PDAC patients to facilitate the
completion of adjuvant chemotherapy.
PMID- 28421349
TI - Predictive detection areas for identifying additional MRI-detected breast lesions
on second-look ultrasonography.
AB - PURPOSE: Identifying an additional MRI-detected breast lesion on second-look
ultrasonography (US) is technically challenging because of lesion displacement
with the patient's position change. The aim of this study is to help identify MRI
detected lesions on second-look US by developing a probing area, called "the
predictive detection area" (PDA), and by assessing the PDA. METHODS: We measured
the nipple-to-lesion distances (NLDs) for 16 breast lesions on prone- and supine
position MRI sets and calculated the difference and angle between the two NLD
vectors, representing the lesion displacement. The minimum and maximum
differences and angles were chosen to form the PDA. Another 22 breast lesions,
detected in the prone MRI, were identified on US by probing the PDA to evaluate
the probability of existence. RESULTS: The width between the minimum and maximum
differences in two NLDs and the angle to form the PDA for the upper-inner, upper
outer, and lower-outer quadrants were 23.0 mm and 95.0 degrees , 29.0 mm and 41.0
degrees , and 18.0 mm and 17.0 degrees , respectively. The respective
probabilities of existence were 100, 80, and 100%. CONCLUSIONS: The PDA had a
high probability of existence and was acceptably accurate; therefore, the PDA in
a second-look US has the potential to help operators to quickly identify
additional MRI-detected lesions.
PMID- 28421350
TI - Preoperative imaging evaluation of pancreatic pathologies for the objective
prediction of pancreatic fistula after pancreaticoduodenectomy.
AB - In performing pancreaticoduodenectomy (PD) or when conducting clinical trials
involving PD procedure, a universal platform for predicting the risk of
postoperative pancreatic fistula (POPF) is indispensable. In this article, the
most significant imaging studies that focused on the objective preoperative
assessment of pancreatic pathologies in association with the occurrence of POPF
after PD were reviewed. Several recently developed imaging modalities can
objectively predict the occurrence of POPF after PD by assessing the elasticity,
fibrosis, and fatty infiltration of the pancreas. These valuable imaging
modalities include: (1) acoustic radiation force impulse ultrasound (US)
electrography which provides information about the elastic properties of the
pancreas; (2) contrast-enhanced computed tomography (CT) and magnetic resonance
imaging (MRI) with/without contrast-enhancement which reflect the histological
degree of pancreatic fibrosis; and (3) multi-detector row CT and/or MRI which
reflects the microscopic fatty infiltration of the pancreas. The precise and
objective preoperative risk assessment of POPF enables surgeons to customize
appropriate management strategies for individual patients undergoing PD. This
would be also beneficial for stratifying patients for enrolment in relevant
studies that involve pancreatic head resection, as objective criteria could be
set for the definitive evaluation of collected data related to surgical outcomes
across different institutions and surgeons.
PMID- 28421351
TI - Characteristics and prognosis of rectal gastrointestinal stromal tumors: an
analysis of registry data.
AB - PURPOSE: Rectal gastrointestinal stromal tumors (GISTs) are rare. Accordingly,
their clinical features are not well-documented and optimal treatment has not
been established. The objective of this study is to clarify the rates and
patterns of recurrence after surgical resection of rectal GISTs, with a focus on
outcomes and therapeutic modalities. METHODS: The registry was designed to
collect data on rectal GISTs recorded between January, 2003 and December, 2007 at
40 participating institutions of the Kinki GIST Study Group. The principal
variables were the rates and patterns of recurrence of rectal GISTs. Other study
variables were age, sex, tumor size, mitotic count, distance from the anal verge,
tumor location, surgical procedures, surgical margins, and recurrence-free
survival. RESULTS: Twenty-four cases were registered, 11 (45.8%) of which were
classified as high-risk by the modified NIH criteria. Locoregional recurrence
(7/23, 30.4%) was the predominant recurrence pattern after curative resection,
with rates that did not differ after local excision (33.3%; 3/9) vs. extended
resection (28.6%; 4/14). The recurrence rates were high (25.0%) even for patients
with low-risk disease. There was only one case of recurrence among patients who
received perioperative treatment with imatinib. CONCLUSIONS: Rectal GISTs showed
high rates of local recurrence regardless of the surgical procedure.
Perioperative treatment with imatinib may improve outcomes.
PMID- 28421352
TI - A New Role of Fine Excipient Materials in Carrier-Based Dry Powder Inhalation
Mixtures: Effect on Deagglomeration of Drug Particles During Mixing Revealed.
AB - The potential of fine excipient materials to improve the performance of carrier
based dry powder inhalation mixtures is well acknowledged. The mechanisms
underlying this potential are, however, open to question till date. Elaborate
understanding of these mechanisms is a requisite for rational rather than
empirical development of ternary dry powder inhalation mixtures. While effects of
fine excipient materials on drug adhesion to and detachment from surfaces of
carrier particle have been extensively investigated, effects on other processes,
such as carrier-drug mixing, capsule/blister/device filling, or aerosolization in
inhaler devices, have received little attention. We investigated the influence of
fine excipient materials on the outcome of the carrier-drug mixing process. We
studied the dispersibility of micronized fluticasone propionate particles after
mixing with alpha-lactose monohydrate blends comprising different fine particle
concentrations. Increasing the fine (D < 10.0 MUm) excipient fraction from 1.84
to 8.70% v/v increased the respirable drug fraction in the excipient-drug mixture
from 56.42 to 67.80% v/v (p < 0.05). The results suggest that low concentrations
of fine excipient particles bind to active sites on and fill deep crevices in
coarse carrier particles. As the concentration of fine excipient particles
increases beyond that saturating active sites, they fill the spaces between and
adhere to the surfaces of coarse carrier particles, creating projections and
micropores. They thereby promote deagglomeration of drug particles during carrier
drug mixing. The findings pave the way for a comprehensive understanding of
contributions of fine excipient materials to the performance of carrier-based dry
powder inhalation mixtures.
PMID- 28421353
TI - Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Infected
Young Russian Women: Comparison to Self-Report Assessments of Alcohol Use.
AB - Alcohol use is particularly deleterious for HIV-infected individuals and thus
accurate assessment of alcohol consumption is crucial in this population.
Phosphatidylethanol (PEth) provides an objective assessment of drinking and can
be compared to self-reported alcohol assessments to detect underreporting. The
purpose of this study was to identify underreporting and its potential predictors
in an HIV-infected sample of young Russian women. The current study examined the
concordance between a quantitative measure of PEth and self-reported recent
alcohol consumption in a prospective sample of HIV-infected young women (N = 204)
receiving medical care in Saint Petersburg, Russia. At baseline, 53% of
participants who denied drinking in the prior 30 days tested positive for PEth
(i.e., underreporters), although this rate decreased significantly at a three
month follow-up assessment. Further exploration did not identify consistent
predictors of underreporting status. Quantitative PEth levels showed, at best,
modest overlap to self-reported alcohol consumption among those reporting alcohol
use (e.g., Spearman's r = 0.27 between PEth and total drinks past-30 days at
baseline). Objective measures of alcohol consumption demonstrate modest overlap
with self-report measures of use in HIV-infected young Russian women.
Incorporating objective and quantifiable biological markers are essential for
valid assessments of alcohol use.
PMID- 28421355
TI - Addressing Early Retention in Antenatal Care Among HIV-Positive Women Through a
Simple Intervention in Kinshasa, DRC: The Elombe "Champion" Standard Operating
Procedure.
AB - This cluster-randomized study aimed to assess the Elombe ("Champion") standard
operating procedure (SOP), implemented by providers and Mentor Mothers, on HIV
positive pregnant women's retention between first and second antenatal visits.
Sixteen facilities in Kinshasa were randomly assigned to intervention (SOP) or
comparison (no SOP). Effect of the SOP was estimated using relative risk. Women
in comparison facilities were more likely to miss second visits (RR 2.5, 95% CI
1.05-5.98) than women in intervention facilities (30.0%, n = 27 vs. 12.0%, n = 9,
p < 0.002). Findings demonstrate that a simple intervention can reduce critical
early loss to care in PMTCT programs providing universal, lifelong treatment.
PMID- 28421354
TI - Perceived Barriers and Facilitators to Integrating HIV Prevention and Treatment
with Cross-Sex Hormone Therapy for Transgender Women in Lima, Peru.
AB - Transgender women (TW) represent a vulnerable population at increased risk for
HIV infection in Peru. A mixed-methods study with 48 TW and 19 healthcare
professionals was conducted between January and February 2015 to explore barriers
and facilitators to implementing a model of care that integrates HIV services
with gender-affirmative medical care (i.e., hormone therapy) in Lima, Peru.
Perceived acceptability of the integrated care model was high among TW and
healthcare professionals alike. Barriers included stigma, lack of provider
training or Peruvian guidelines regarding optimal TW care, and service delivery
obstacles (e.g., legal documents, spatial placement of clinics, hours of
operation). The hiring of TW staff was identified as a key facilitator for
engagement in health care. Working in partnership with local TW and healthcare
provider organizations is critical to overcoming existing barriers to successful
implementation of an integrated HIV services and gender-affirmative medical care
model for this key population in Peru.
PMID- 28421356
TI - The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel
Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in
Resource-Limited Settings.
AB - Although mobile health (mHealth) technologies have shown promise in improving
clinical care in resource-limited settings (RLS), they are infrequently brought
to scale. One limitation to the success of many mHealth interventions is
inattention to end-user acceptability, which is an important predictor of
technology adoption. We conducted in-depth interviews with 43 people living with
HIV in rural Uganda who had participated in a clinical trial of a short messaging
system (SMS)-based intervention designed to prompt return to clinic after an
abnormal laboratory test. Interviews focused on established features of
technology acceptance models, including perceived ease of use and perceived
usefulness, and included open-ended questions to gain insight into unexplored
issues related to the intervention's acceptability. We used conventional
(inductive) and direct content analysis to derive categories describing use
behaviors and acceptability. Interviews guided development of a proposed
conceptual framework, the technology acceptance model for resource-limited
settings (TAM-RLS). This framework incorporates both classic technology
acceptance model categories as well as novel factors affecting use in this
setting. Participants described how SMS message language, phone characteristics,
and experience with similar technologies contributed to the system's ease of use.
Perceived usefulness was shaped by the perception that the system led to
augmented HIV care services and improved access to social support from family and
colleagues. Emergent themes specifically related to mHealth acceptance among PLWH
in Uganda included (1) the importance of confidentiality, disclosure, and stigma,
and (2) the barriers and facilitators downstream from the intervention that
impacted achievement of the system's target outcome. The TAM-RLS is a proposed
model of mHealth technology acceptance based upon end-user experiences in rural
Uganda. Although the proposed model requires validation, the TAM-RLS may serve as
a useful tool to guide design and implementation of mHealth interventions.
PMID- 28421357
TI - Incidence of autoimmune diseases in patients with scabies: a nationwide
population-based study in Taiwan.
AB - Scabies is a commonly occurring infectious immune-mediated inflammatory skin
disease. Immune-mediated inflammatory processes are also observed in autoimmune
diseases. There have been very few previous studies; however, that have
investigated the possible association between scabies and autoimmune diseases. To
address this research gap, we conducted a nationwide population-based cohort
study that included a total of 4481 scabies patients and 16,559 control subjects
matched by gender, age, insured region, urbanization and income. We tracked both
cohorts for a 7-year period to identify the incidence of autoimmune diseases in
both groups during that follow-up period. Relatedly, a Cox regression analysis
was performed to calculate and compare the hazard ratio (HR) for autoimmune
diseases of both groups. An overall increased risk for 19 autoimmune diseases was
observed in the scabies patients, with an adjusted HR (aHR) of 1.14 (95% CI 1.04
1.25). Compared with the control group, the scabies patients exhibited increased
risks of hypersensitivity vasculitis (aHR 5.44, 95% CI 1.64-18.07),
dermatomyositis (aHR 4.91, 95% CI 1.80-13.38), polyarteritis nodosa (aHR 2.89,
95% CI 1.46-5.73), systemic lupus erythematosus (aHR 2.73, 95% CI 1.33-5.64),
psoriasis (aHR 2.31, 95% CI 1.85-2.88), myasthenia gravis (aHR 2.01, 95% CI 1.31
3.12), type 1 diabetes mellitus (aHR 1.93, 95% CI 1.53-2.44), pernicious anemia
(aHR 1.92, 95% CI 1.42-2.61), and rheumatoid arthritis (aHR 1.43, 95% CI 1.12
1.83). In conclusion, the associations between scabies and a variety of
autoimmune diseases may exist. Further studies are needed to clarify the shared
etiologies and relationships between scabies and autoimmune diseases.
PMID- 28421358
TI - Vitamin D supplementation for the management of knee osteoarthritis: a systematic
review of randomized controlled trials.
AB - Conflicting evidence exists concerning the supplementation of vitamin D in knee
osteoarthritis condition. This systematic literature review was done to explore
the effects of vitamin D supplementation in the management of knee
osteoarthritis. Electronic literature search was done in databases like
PubMed(r), Embase(r), and Cochrane CENTRAL from inception to 6th July 2016. The
quality of included Randomized Controlled Trials (RCTs) was assessed using
Cochrane risk of bias tool. We considered change in Western Ontario and McMaster
Universities (WOMAC) index, Visual Analog Scale (VAS) and Functional Pain Score
(FPS) as the primary outcome measure. Change in tibial cartilage thickness, joint
space width and safety profile was considered as secondary outcomes. Participants
were randomized either to treatment or placebo group. Participants received
cholecalciferol as an intervention through oral route in the dose range of 800
60,000 IU except in the one study where participants received ergocalciferol. All
included RCTs showed a significant increase in serum vitamin D level in the
treatment group compared to the placebo group at the end point. No significant
reduction in pain and function was reported on WOMAC scale except in one study.
No significant difference was reported for WOMAC stiffness in any study. VAS was
assessed in three studies in which two showed statistically significant
improvement in knee pain. Three of the RCTs reported safety data with one
incidence of calculus ureteric and hip fracture found to be related to the drug.
The study found evidence from RCTs to be insufficient to support the use of
vitamin D supplementation for patients with knee osteoarthritis.
PMID- 28421359
TI - The theory of planned behaviour explains intentions to use antiresorptive
medication after a fragility fracture.
AB - Our objective was to ascertain whether the Theory of Planned Behaviour (TPB)
explains patient intentions to use antiresorptive medication after a fracture. A
qualitative study was conducted with English-speaking members of the Canadian
Osteoporosis Patient Network (COPN) who had sustained a fragility fracture at 50+
years of age and were not taking antiresorptive medication at the time of that
fracture. Questions during a 1-h telephone interview were guided by the domains
of the TPB: they addressed the antecedent constructs regarding antiresorptive
medication (attitudes, subjective norms, and perceived behavioural control) as
well as intentions regarding antiresorptive medication use. We created a coding
template a priori based on the TPB domains and applied this template to the
interview data. Twenty-six eligible participants (24 females, 2 males) aged 51-89
completed an interview. The TPB appeared to be predictive of intentions in 19
(73%) participants. In the majority of participants where the TPB did not appear
to be predictive (57%), a positive attitude toward antiresorptive medication was
the most important antecedent variable in determining intentions. The TPB
appeared to be predictive of intentions to use antiresorptive medication among
individuals who had experienced a fragility fracture. Attitudes towards
medication were especially important.
PMID- 28421360
TI - Update on Chemotherapy-Induced Peripheral Neuropathy.
AB - PURPOSE OF REVIEW: The purpose of this study was to briefly discuss chemotherapy
induced peripheral neuropathy (CIPN) and detail the most important and most
recent chemotherapeutic agents implicated. This review will examine neuropathy
mechanisms, risk factors, and clinical patterns; novel and prospective drugs with
similar effects that are less well known to neurologists are discussed. RECENT
FINDINGS: CIPN is increasingly recognized for its clinical importance and effect
on patient quality of life. Identification of risk factors is ongoing and may
enable future risk stratification. Newer classes of agents and new members of
existing classes are continually recognized, notably immune check point
inhibitors, other monoclonal antibody treatments, novel immunomodulatory agents,
and proteasome inhibitors. Advances regarding established classes including
taxanes, platins, and vinca alkaloids are also reviewed. CIPN is an important
often dose-limiting toxicity. Multiple agents cause neuropathy; various clinical
patterns are described. Future studies should aim at improved understanding of
toxicity mechanisms and development of preventive and therapeutic strategies.
PMID- 28421361
TI - Erratum to: A comparative study of the bone contact to zirconium and titanium
implants after 8 weeks of implantation in rabbit femoral condyles.
PMID- 28421362
TI - Selective Imaging of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2
in Atherosclerotic Lesions in Diabetic and Non-diabetic ApoE-/- Mice.
AB - PURPOSE: Plaque vulnerability is associated with inflammation and angiogenesis,
processes that rely on vascular endothelial growth factor (VEGF) signaling via
two receptors, VEGFR-1 and VEGFR-2. We have recently reported that enhanced
uptake of scVEGF-PEG-DOTA/Tc-99m (scV/Tc) single photon emission computed
tomography (SPECT) tracer that targets both VEGFR-1 and VEGFR-2, identifies
accelerated atherosclerosis in diabetic relative to non-diabetic ApoE-/- mice.
Since VEGFR-1 and VEGFR-2 may play different roles in atherosclerotic plaques, we
reasoned that selective imaging of each receptor can provide more detailed
information on plaque biology. PROCEDURES: Recently described VEGFR-1 and VEGFR-2
selective mutants of scVEGF, named scVR1 and scVR2, were site-specifically
derivatized with Tc-99m chelator DOTA via 3.4 kDa PEG linker, and their
selectivity to the cognate receptors was confirmed in vitro. scVR1 and scVR2
conjugates were radiolabeled with Tc-99m to specific activity of 110 +/- 11
MBq/nmol, yielding tracers named scVR1/Tc and scVR2/Tc. 34-40 week old diabetic
and age-matched non-diabetic ApoE-/- mice were injected with tracers, 2-3 h later
injected with x-ray computed tomography (CT) contrast agent and underwent hybrid
SPECT/CT imaging. Tracer uptake, localized to proximal aorta and brachiocephalic
vessels, was quantified as %ID from. Tracer uptake was also quantified as %ID/g
from gamma counting of harvested plaques. Harvested atherosclerotic arterial
tissue was used for immunofluorescent analyses of VEGFR-1 and VEGFR-2 and various
lineage-specific markers. RESULTS: Focal, receptor-mediated uptake in proximal
aorta and brachiocephalic vessels was detected for both scVR1/Tc and scVR2/Tc
tracers. Uptake of scVR1/Tc and scVR2/Tc was efficiently inhibited only by "cold"
proteins of the same receptor selectivity. Tracer uptake in this area, expressed
as %ID, was higher in diabetic vs. non- diabetic mice for scVR1/Tc (p = 0.01) but
not for scVR2/Tc. Immunofluorescent analysis revealed enhanced VEGFR-1 prevalence
in and around plaque area in diabetic mice. CONCLUSIONS: Selective VEGFR-1 and
VEGFR-2 imaging of atherosclerotic lesions may be useful to explore plaque
biology and identify vulnerability.
PMID- 28421363
TI - Response to Dr. Hawkes letter regarding HPV vaccine serious adverse events.
PMID- 28421364
TI - An ovine in vivo framework for tracheobronchial stent analysis.
AB - Tracheobronchial stents are most commonly used to restore patency to airways
stenosed by tumour growth. Currently all tracheobronchial stents are associated
with complications such as stent migration, granulation tissue formation, mucous
plugging and stent strut fracture. The present work develops a computational
framework to evaluate tracheobronchial stent designs in vivo. Pressurised
computed tomography is used to create a biomechanical lung model which takes into
account the in vivo stress state, global lung deformation and local loading from
pressure variation. Stent interaction with the airway is then evaluated for a
number of loading conditions including normal breathing, coughing and
ventilation. Results of the analysis indicate that three of the major
complications associated with tracheobronchial stents can potentially be analysed
with this framework, which can be readily applied to the human case. Airway
deformation caused by lung motion is shown to have a significant effect on stent
mechanical performance, including implications for stent migration, granulation
formation and stent fracture.
PMID- 28421365
TI - Grass carp reovirus outer capsid proteins VP5 and VP7 interact in vitro.
AB - Grass carp reovirus (GCRV) causes viral hemorrhagic disease in cultured grass
carp. However, there is no effective means of controlling GCRV. Previous studies
have shown, by cryoelectron microscopy, that the outer capsid of GCRV is composed
of 200 trimers of VP5-VP7 heterodimers. However, confirmation of this interaction
between VP5 and VP7 through molecular biochemistry is still lacking. This study
characterized the interactions between VP5 and VP7 in vitro. VP5 was shown to
interact with VP7 in a commercial yeast-two-hybrid screen. A dot-blot overlay
assay was used to show that VP7 binding to VP5 was dose-dependent. Finally, a
yeast-two-hybrid approach confirmed interactions between full-length and
truncated forms of VP5 and VP7. In conclusion, our results indicate that VP5 and
VP7 interact directly in vitro.
PMID- 28421366
TI - Two deletion variants of Middle East respiratory syndrome coronavirus found in a
patient with characteristic symptoms.
AB - Significant sequence variation of Middle East respiratory syndrome coronavirus
(MERS CoV) has never been detected since it was first reported in 2012. A MERS
patient came from Korea to China in late May 2015. The patient was 44 years old
and had symptoms including high fever, dry cough with a little phlegm, and
shortness of breath, which are roughly consistent with those associated with
MERS, and had had close contact with individuals with confirmed cases of
MERS.After one month of therapy with antiviral, anti-infection, and immune
enhancing agents, the patient recovered in the hospital and was discharged. A
nasopharyngeal swab sample was collected for direct sequencing, which revealed
two deletion variants of MERS CoV. Deletions of 414 and 419 nt occurred between
ORF5 and the E protein, resulting in a partial protein fusion or truncation of
ORF5 and the E protein. Functional analysis by bioinformatics and comparison to
previous studies implied that the two variants might be defective in their
ability to package MERS CoV. However, the mechanism of how these deletions
occurred and what effects they have need to be further investigated.
PMID- 28421367
TI - NS3 protease resistance-associated substitutions in liver tissue and plasma
samples from patients infected by hepatitis C virus genotype 1A or 1B.
AB - The presence of naturally occurring resistance-associated substitutions (RASs) in
the HCV-protease domain has been poorly investigated in the liver, the main site
of HCV replication. We evaluated the natural resistance of the virus to NS3
protease inhibitors in liver tissue and plasma samples taken from HCV-infected
patients. RASs were investigated by means of viral population sequencing in liver
tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype
1b; plasma samples from 12 of these patients were also available for virological
investigation. A discordant genotype was found in two of the 12 patients (16.6%)
who provided samples from both compartments. Sequence analysis of the NS3
protease domain showed the presence of RASs in four of the 18 liver tissue
samples (22.2%), two of which showed cross-resistance to protease inhibitors in
clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and
plasma samples excluded the presence of RASs in the plasma compartment. The
dominance of discordant genotypes in the paired liver and plasma samples of some
HCV-infected patients suggests mixed infection possibly leading to the selective
advantage of different genotype in the two compartments. The presence of RASs at
intra-hepatic level is not uncommon and may lead to the early emergence of cross
resistant strains.
PMID- 28421368
TI - Recombinant foot-and-mouth disease virus (FMDV) non-structural protein 3A fused
to enhanced green fluorescent protein (EGFP) as a candidate probe to identify
FMDV-infected cattle in serosurveys.
AB - Recombinant protein 3A-EGFP, a fusion construct between foot-and-mouth disease
virus (FMDV) non-structural protein 3A and the enhanced green fluorescent protein
(EGFP) was expressed in BL21-DE3 cells. The identity of the partially purified
protein 3A-EGFP was confirmed by its reactivity with sera from cattle infected
with FMDV and with a monoclonal antibody specific for FMDV-3ABC (MAb3H7) in
Western blot assays. No reactivity was observed with sera from uninfected
vaccinated animals. The performance of 3A-EGFP as an antigen in an indirect
enzyme-linked immunosorbent assay (ELISA) was assessed and compared with that of
a previously developed and validated capture ELISA that uses a 3ABC recombinant
antigen (3ABC ELISA) and has been widely applied for serological surveys in
Argentina. Parallel analysis of strongly and weakly positive reference sera from
infected animals and 329 serum samples from uninfected vaccinated cattle showed
that the 3A-EGFP antigen unequivocally identifies sera from FMDV-infected cattle
with similar performance to its 3ABC counterpart. The 3A-EGFP ELISA is simpler
and faster to perform than the 3ABC ELISA, since it does not require a capture
step with a specific antibody. Moreover, the expression and storage of the
recombinant 3A-EGFP is simplified by the absence of residual autoproteolytic
activity associated to the 3C sequence. We conclude that the 3A-EGFP ELISA
constitutes a promising screening method in serosurveys to determine whether or
not animals are infected with FMDV.
PMID- 28421369
TI - Immunophenotypic profiles for distinguishing orbital mucosa-associated lymphoid
tissue lymphoma from benign lymphoproliferative tumors.
AB - PURPOSE: To evaluate novel immunophenotypic profiles of patients with orbital
lymphoproliferative tumors. METHODS: From 2006 to 2014, surgical biopsies from
consecutive patients with newly diagnosed orbital mucosa-associated lymphoid
tissue (MALT) lymphoma and IgG4-related ophthalmic disease (IgG4-ROD) were
collected from Tokyo Medical University Hospital. A total of 44 tumors from 44
patients were analyzed, including 21 with orbital MALT lymphoma (11 men and 10
women, mean age 67.8 +/- 13.4 years) and 23 with definitive IgG4-ROD (9 men and
14 women, mean age 60.5 +/- 15.1 years). Patients with secondary orbital MALT
lymphoma and MALT lymphoma with IgG4-ROD were excluded. All patients were
immunocompetent Asian adults. Samples were analyzed by immunohistochemistry and
flow cytometric analysis. Flow cytometry was performed with the following
antibodies: CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, CD25, CD30, CD34, and
CD56 lambda and kappa chains. RESULTS: Expression of CD25 and CD19 was higher in
patients with orbital MALT lymphoma compared to patients with IgG4-ROD (p <
0.001). In contrast, expression of CD3, CD4, and CD23 was higher in patients with
orbital IgG4-ROD compared to those with MALT lymphoma (all p < 0.01). The
presence of CD23 and CD25 in the specimens was confirmed by immunohistochemistry.
CONCLUSION: The present study elucidated the novel immunophenotypic features of
orbital MALT and benign lymphoproliferative disorders such as IgG4-ROD. Among
them, CD23 and CD25 have shown a disease-specific expression pattern.
PMID- 28421371
TI - Temperature-dependent signal transmission in chloroplast accumulation response.
AB - Chloroplast photorelocation movement, well-characterized light-induced response
found in various plant species from alga to higher plants, is an important
phenomenon for plants to increase photosynthesis efficiency and avoid
photodamage. The signal for chloroplast accumulation movement connecting the blue
light receptor, phototropin, and chloroplasts remains to be identified, although
the photoreceptors and the mechanism of movement via chloroplast actin filaments
have now been revealed in land plants. The characteristics of the signal have
been found; the speed of signal transfer is about 1 um min-1 and that the signal
for the accumulation response has a longer life and is transferred a longer
distance than that of the avoidance response. Here, to collect the clues of the
unknown signal substances, we studied the effect of temperature on the speed of
signal transmission using the fern Adiantum capillus-veneris and found the
possibility that the mechanism of signal transfer was not dependent on the simple
diffusion of a substance; thus, some chemical reaction must also be involved. We
also found new insights of signaling substances, such that microtubules are not
involved in the signal transmission, and that the signal could even be
transmitted through the narrow space between chloroplasts and the plasma
membrane.
PMID- 28421370
TI - The current state of knowledge on the neuroactive compounds that affect the
development, mating and reproduction of spiders (Araneae) compared to insects.
AB - The neuroendocrine system of insects, including the presence of the main
neuroactive compounds, and their role in ontogenesis are probably best understood
of all the arthropods. Development, metamorphosis, the maturation of the gonads,
vitellogenesis and egg production are regulated by hormones (juvenile hormones,
ecdysteroids) and neuropeptides. However, knowledge about their presence and
functions in spiders is fragmentary. In this paper, we present a summary of the
current data about the juvenile hormones, ecdysteroids and neuropeptides in
selected groups of arthropods, with particular emphasis on spiders. This is the
first article that takes into account the occurrence, action and role of hormones
and neuropeptides in spiders. In addition, the suggestions for possible ways to
study these compounds in Araneomorphae spiders are unique and cannot be found in
the arachnological literature.
PMID- 28421372
TI - Vascular development of the grapevine (Vitis vinifera L.) inflorescence rachis in
response to flower number, plant growth regulators and defoliation.
AB - The grapevine inflorescence is a determinate panicle and as buds emerge, shoot,
flower and rachis development occur simultaneously. The growth and architecture
of the rachis is determined by genetic and environmental factors but here we
examined the role of flower and leaf number as well as hormones on its elongation
and vascular development. The consequences of rachis morphology and vascular area
on berry size and composition were also assessed. One week prior to anthesis,
Merlot and Cabernet Sauvignon field vines were exposed to manual flower removal,
exogenous plant growth regulators or pre-bloom leaf removal. Manual removal of
half the flowers along the vertical axis of the inflorescence resulted in a
shorter rachis in both cultivars. Conversely, inflorescences treated with
gibberellic acid (GA3) and the synthetic cytokinin, 6-benzylaminopurine (BAP)
resulted in a longer rachis while pre-bloom removal of all leaves on the
inflorescence-bearing shoot did not alter rachis length relative to untreated
inflorescences. Across the treatments, the cross-sectional areas of the
conducting xylem and phloem in the rachis were positively correlated to rachis
girth, flower number at anthesis, bunch berry number, bunch berry fresh mass and
bunch sugar content at harvest. Conversely, average berry size and sugar content
were not linked to rachis vascular area. These data indicate that the
morphological and vascular development of the rachis was more responsive to
flower number and plant growth regulators than to leaf removal.
PMID- 28421373
TI - Role of glycogen synthase kinase following myocardial infarction and ischemia
reperfusion.
AB - Glycogen synthase kinase-3 beta (GSK3beta) is principally is a glycogen synthase
phosphorylating enzyme that is well known for its role in muscle metabolism.
GSK3beta is a serine/threonine protein Kinase, which is responsible for several
essential roles in mammalian cells. This enzyme is implicated in the
pathophysiology of many conditions involved in homeostasis and cellular
immigration. GSK3beta is involved in several pathways leading to
neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
Increasing evidence has shown the potential importance of GSK3beta in ischemic
heart disease and ischemia-reperfusion pathologies. Reperfusion injury may occur
in tissues after prolonged ischemia following reperfusion. Reperfusion injury can
be life threatening. Reperfusion injury occurs due to a change in ionic
homeostasis, excess free radical production, mitochondrial damage and cell death.
There are however clear, cardiac-protective signals; although the molecular
pathophysiology is not clearly understood. In normal physiology, GSK3beta has a
critical role in the cytoprotective pathway. However, it's controversial role in
ischemia and ischemia-reperfusion is a topic of current interest. In this review,
we have opted to focus on GSK3beta interactions with mitochondria in ischemic
heart disease and expand on the therapeutic interventions.
PMID- 28421374
TI - Level of physical activity, well-being, stress and self-rated health in persons
with migraine and co-existing tension-type headache and neck pain.
AB - BACKGROUND: The prevalence of migraine with co-existing tension-type headache and
neck pain is high in the general population. However, there is very little
literature on the characteristics of these combined conditions. The aim of this
study was to investigate a) the prevalence of migraine with co-existing tension
type headache and neck pain in a clinic-based sample, b) the level of physical
activity, psychological well-being, perceived stress and self-rated health in
persons with migraine and co-existing tension-type headache and neck pain
compared to healthy controls, c) the perceived ability of persons with migraine
and co-existing tension-type headache and neck pain to perform physical activity,
and d) which among the three conditions (migraine, tension-type headache or neck
pain) is rated as the most burdensome condition. METHODS: The study was conducted
at a tertiary referral specialised headache centre where questionnaires on
physical activity, psychological well-being, perceived stress and self-rated
health were completed by 148 persons with migraine and 100 healthy controls
matched by sex and average age. Semi-structured interviews were conducted to
assess characteristics of migraine, tension-type headache and neck pain. RESULTS:
Out of 148 persons with migraine, 100 (67%) suffered from co-existing tension
type headache and neck pain. Only 11% suffered from migraine only. Persons with
migraine and co-existing tension-type headache and neck pain had lower level of
physical activity and psychological well-being, higher level of perceived stress
and poorer self-rated health compared to healthy controls. They reported reduced
ability to perform physical activity owing to migraine (high degree), tension
type headache (moderate degree) and neck pain (low degree). The most burdensome
condition was migraine, followed by tension-type headache and neck pain.
CONCLUSIONS: Migraine with co-existing tension-type headache and neck pain was
highly prevalent in a clinic-based sample. Persons with migraine and co-existing
tension-type headache and neck pain may require more individually tailored
interventions to increase the level of physical activity, and to improve
psychological well-being, perceived stress and self-rated health.
PMID- 28421375
TI - Obstructive sleep apnea increases the risk of cardiac events after percutaneous
coronary intervention: a meta-analysis of prospective cohort studies.
AB - PURPOSE: Recent studies have shown an association between obstructive sleep apnea
(OSA) and coronary artery disease; however, the association between OSA and
cardiac outcomes in patients after percutaneous coronary intervention (PCI)
remains undetermined. METHODS: PubMed, EMBASE, and CENTRAL were searched from
inception to July 2016 for cohort studies that followed up with patients after
PCI, and evaluated their overnight sleep patterns within 1 month for major
adverse cardiac events (MACEs) as primary outcomes including cardiac death, non
fatal myocardial infarction (MI), and coronary revascularization and secondary
outcomes including re-admission for heart failure and stroke. Outcomes data were
pooled using fixed-effect meta-analysis, and heterogeneity was assessed with the
I 2 statistics. The methodological quality of the studies was assessed using the
Newcastle-Ottawa Scale checklist, and publication bias was evaluated by a visual
investigation of funnel plots. RESULTS: We identified seven pertinent studies
including 2465 patients from 178 related articles. OSA was associated with MACEs
(odds ratio [OR], 1.52, 95% confidence interval [CI], 1.20-1.93, I 2 = 29%),
which included cardiac death (OR 2.05, 95% CI, 1.15-3.65, I 2 = 0%), non-fatal MI
(OR 1.59, 95% CI, 1.14-2.23, I 2 = 15%), and coronary revascularization (OR 1.69,
95% CI, 1.28-2.23, I 2 = 0%). However, OSA was not associated with re-admission
for heart failure (OR 1.71, 95% CI, 0.99-2.96, I 2 = 0%) and/or stroke (OR 1.68,
95% CI, 0.91-3.11, I 2 = 0%) according to the pooled results. CONCLUSIONS: In
patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal
MI, and coronary revascularization.
PMID- 28421376
TI - Using the STOPBANG questionnaire and other pre-test probability tools to predict
OSA in younger, thinner patients referred to a sleep medicine clinic.
AB - BACKGROUND: The STOPBANG questionnaire is used to predict the presence of
obstructive sleep apnea (OSA). We sought to assess the performance of the
STOPBANG questionnaire in younger, thinner patients referred to a sleep medicine
clinic. METHODS: We applied the STOPBANG questionnaire to patients referred for
level I polysomnography (PSG) at our sleep center. We calculated likelihood
ratios and area under the receiver operator characteristic (AUROC) curve and
performed sensitivity analyses. RESULTS: We performed our analysis on 338
patients referred for PSG. Only 17.2% (n = 58) were above age 50 years, and 30.5
and 6.8% had a BMI above 30 and 35 years, respectively. The mean apnea-hypopnea
index (AHI) was 12.9 +/- 16.4 and 63.9% had an AHI >=5. The STOPBANG (threshold
>=3) identified 83.1% of patients as high risk for an AHI >=5, and sensitivity,
specificity, positive (PPV), and negative predictive values (NPV) were 83.8,
18.0, 64.4, and 38.0%, respectively. Positive and negative likelihood ratios were
poor at 1.02-1.11 and 0.55-0.90, respectively, across AHI thresholds (AHI >=5,
AHI >=15 and AHI >=30), and AUROCs were 0.52 (AHI >=5) and 0.56 (AHI >=15).
Sensitivity analyses adjusting for insomnia, combat deployment, traumatic brain
injury, post-traumatic stress disorder, clinically significant OSA (ESS >10
and/or co-morbid disease), and obesity did not significantly alter STOPBANG
performance. CONCLUSIONS: In a younger, thinner population with predominantly
mild-to-moderate OSA, the STOPBANG Score does not accurately predict the presence
of obstructive sleep apnea.
PMID- 28421377
TI - VEP and PERG in patients with multiple sclerosis, with and without a history of
optic neuritis.
AB - PURPOSE: Visual electrophysiology is routinely used to detect the visual
complications of multiple sclerosis, but the analysis mostly focuses on visual
evoked potential (VEP) and especially the P100 component. Our goal was to analyze
the components and waveform alterations of VEPs and pattern electroretinograms
(PERGs) in patients with multiple sclerosis (MS) with good vision. METHODS: The
main VEP and PERG components of 85 patients with MS were analyzed in two groups:
38 patients who had optic neuritis in their history (ON group) and 47 patients
who had never had optic neuritis (MS group). The results were compared against a
control group of 47 healthy subjects. RESULTS: Both VEP and PERG alterations
occurred in a greater number of patients than expected, and these alterations
were not necessarily linked to ON in the history or a deterioration of visual
acuity. CONCLUSIONS: Both VEP and PERG can detect dysfunction in the visual
system in MS, even if the patient has no subjective symptoms. Even if PERG is not
routinely used in neuro-ophthalmology, the results suggest that PERG assessment
may provide useful information describing the retinal defect in MS.
PMID- 28421379
TI - Role of taxanes in chemotherapy-related cognitive impairment: A prospective
longitudinal study.
AB - PURPOSE: The aim of this study is to elucidate the role of taxanes on cognition
when they are administered as a part of the treatment with a fluorouracil,
epirubicin and cyclophosphamide (FEC) regimen for breast cancer (BC). METHODS:
Two groups of women (n = 51) with a novel diagnostic of BC that were treated with
a combination of FEC alone (6 cycles of FEC) or with taxanes (4 cycles of FEC
plus 8 cycles of taxanes) were compared at three moments: before chemotherapy,
after its completion (short-term evaluation) and at a mean of 74.5 weeks from
baseline as a long-term evaluation. RESULTS: Both groups showed worsening in
tests of attention and executive functions on the short-term assessment, with the
group treated with taxanes showing more number of affected cognitive measures at
this time point, including verbal learning and speed measures. At the long-term
evaluation, cognitive dysfunction was still found in attention and executive
functions in both groups. CONCLUSION: Our results suggest that chemotherapy for
BC with a FEC regimen can have a negative effect on cognition. Acute deficits
seem to be larger when taxanes are added, but treatment seems to affect cognition
also at long term.
PMID- 28421378
TI - Transcriptome-Based Identification of the Desiccation Response Genes in Marine
Red Algae Pyropia tenera (Rhodophyta) and Enhancement of Abiotic Stress Tolerance
by PtDRG2 in Chlamydomonas.
AB - Pyropia tenera (Kjellman) are marine red algae that grow in the intertidal zone
and lose more than 90% of water during hibernal low tides every day. In order to
identify the desiccation response gene (DRG) in P. tenera, we generated 1,444,210
transcriptome sequences using the 454-FLX platform from the gametophyte under
control and desiccation conditions. De novo assembly of the transcriptome reads
generated 13,170 contigs, covering about 12 Mbp. We selected 1160 differentially
expressed genes (DEGs) in response to desiccation stress based on reads per
kilobase per million reads (RPKM) expression values. As shown in green higher
plants, DEGs under desiccation are composed of two groups of genes for gene
regulation networks and functional proteins for carbohydrate metabolism, membrane
perturbation, compatible solutes, and specific proteins similar to higher plants.
DEGs that show no significant homology with known sequences in public databases
were selected as DRGs in P. tenera. PtDRG2 encodes a novel polypeptide of 159
amino acid residues locating chloroplast. When PtDRG2 was overexpressed in
Chlamydomonas, the PtDRG2 confer mannitol and salt tolerance in transgenic cells.
These results suggest that Pyropia may possess novel genes that differ from green
plants, although the desiccation tolerance mechanism in red algae is similar to
those of higher green plants. These transcriptome sequences will facilitate
future studies to understand the common processes and novel mechanisms involved
in desiccation stress tolerance in red algae.
PMID- 28421380
TI - Revisiting Mechanisms of Extraterritorial Allodynia.
PMID- 28421382
TI - Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase
(MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma
Treated with FOLFIRINOX.
AB - BACKGROUND: To date, no predictive biomarker for the efficacy of FOLFIRINOX in
metastatic pancreatic adenocarcinoma has been demonstrated. Deficiency in O6
methylguanine-DNA methyltransferase (MGMT) has been associated with a therapeutic
response in endocrine tumors of the pancreas and the lack of expression of
protein 53 (p53) could interfere with the action of MGMT. OBJECTIVE: The aim of
our study was to assess the prevalence of MGMT and p53 in patients with
metastatic pancreatic adenocarcinoma treated with FOLFIRINOX as a first-line
treatment and to investigate their association with therapeutic response and
survival. PATIENTS AND METHODS: The immunohistochemical expression of MGMT was
recorded as present or absent and the expression of p53 was semi-quantitatively
scored in 30 patients with metastatic pancreatic adenocarcinoma, at Angers
Hospital in France between September 2011 and June 2015. Clinical and radiologic
data were collected retrospectively. RESULTS: The presence or absence of MGMT
expression entailed no significant differences in response rate. Median values of
progression-free survival (PFS) and overall survival (OS) were lower in patients
with MGMT expression, but sample size is too small to conclude that there is a
statistically significant difference. No significant relationship for response
rate and PFS was observed in relation with p53 expression. By contrast, patients
with a strong tumor expression of p53 had a significantly lower OS compared to
patients with no or weak expression of the protein (p = 0.027). There was a
positive correlation between the expression of p53 and MGMT (p = 0.08).
CONCLUSIONS: These preliminary findings suggest that for patients treated with
FOLFIRINOX as a first-line treatment for metastatic pancreatic adenocarcinoma,
the immunohistochemical evaluation of MGMT could not predict the clinical
outcome; however, the survival was not significant probably because of the under
powered study (due to small sample size). A strong tumor expression of p53 is
associated with a poor prognosis of OS.
PMID- 28421383
TI - Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of
Guanfacine Extended-Release Formulation in Healthy Japanese and Caucasian Male
Adults.
AB - BACKGROUND AND OBJECTIVE: Guanfacine extended-release (guanfacine XR) could be a
useful treatment option for children and adolescent patients with attention
deficit/hyperactivity disorder (ADHD). As an initial step in the development in
Japan, the pharmacokinetics, safety and tolerability were assessed in healthy
Japanese and non-Hispanic Caucasian adults. METHODS: A Phase 1, double-blind,
randomized, placebo-controlled, single- and multiple-oral dose escalation study
of guanfacine XR was conducted. Healthy Japanese and Caucasian subjects received
guanfacine XR 1 mg orally in the morning on Day 1. Following safety assessments,
subjects subsequently received guanfacine XR 1 mg (Days 4-8), 2 mg (Days 9-13), 3
mg (Days 14-18), and 4 mg (Days 19-23) once daily, followed by a taper-down
period. Single- and multiple-dose pharmacokinetic parameters were estimated based
on plasma concentration-time data and urine concentration data of guanfacine by
non-compartmental analysis. RESULTS: A total of 30 male subjects (15 Japanese and
15 Caucasian, active:placebo = 12:3) were enrolled. Of those receiving guanfacine
XR, 11/12 (91.7%) subjects in each active drug group completed the study.
Following multiple doses, the mean area under the plasma concentration-time
curves of guanfacine were 9-22% greater for Caucasian subjects than Japanese
subjects in the 1-3 mg dose range and 54% greater for the 4 mg. Guanfacine XR was
generally well tolerated by both ethnic groups, with most adverse events being
mild in both groups. There were no serious or severe adverse events during the
study and no adverse events led to withdrawal from the study. CONCLUSIONS:
Exposure to guanfacine in Japanese subjects tended to be lower than in Caucasian
subjects. Guanfacine XR was generally well tolerated and safety profiles were
similar for Japanese and Caucasian subjects.
PMID- 28421381
TI - Lactase Non-persistence and Lactose Intolerance.
AB - PURPOSE OF REVIEW: To evaluate the clinical and nutritional significance of
genetically determined lactase non-persistence and potential lactose and milk
intolerance in 65-70% of the world's adult population. RECENT FINDINGS: Milk
consumption is decreasing in the USA and is the lowest in countries with a high
prevalence of lactase non-persistence. The dairy industry and Minnesota
investigators have made efforts to minimize the influence of lactose intolerance
on milk consumption. Some lactose intolerant individuals, without co-existent
irritable bowel syndrome, are able to consume a glass of milk with a meal with no
or minor symptoms. The high frequency of lactase persistence in offspring of
Northern European countries and in some nomadic African tribes is due to
mutations in the promoter of the lactase gene in association with survival
advantage of milk drinking. Educational and commercial efforts to improve calcium
and Vitamin D intake have focused on urging consumption of tolerable amounts of
milk with a meal, use of lowered lactose-content foods including hard cheeses,
yogurt, and lactose-hydrolyzed milk products.
PMID- 28421384
TI - The efficacy of Guolin-Qigong on the body-mind health of Chinese women with
breast cancer: a randomized controlled trial.
AB - PURPOSE: This study was to evaluate the efficacy of a complementary Chinese
treatment modality Guolin-Qigong (GLQG) for patients with breast cancer on the
body-mind health. METHODS: A randomized controlled clinical trial was conducted
among 158 women with breast cancer. Subjects were randomized to receive GLQG
(test group) versus a physical stretching program (control group) following
conventional treatment for breast cancer. GLQG and stretching interventions were
performed twice a week over 24 weeks. The primary outcome was the change in
quality of life (QoL). Secondary outcome measures included anxiety, depression,
and clinical indicators. All participants were assessed at four time-points, at
the beginning of the study (T1), after 12 weeks of the intervention (T2),
immediately after 24-week intervention (T3), and at 48-week follow-up visit (T4).
RESULTS: Improvements in QoL were evident in both groups but the test group fared
better than the control group at the 12th week (P < 0.01) and particularly in
emotional well-being (P < 0.01) and breast cancer-specific well-being (P <
0.001). The test group showed an improvement in anxiety levels (P < 0.01),
whereas the control group showed improvements in depression (P < 0.05) but there
was no significant difference between groups (P > 0.05). Both groups showed
improvements in immunological function and the test group fared better than the
control in TNF-alpha levels (P < 0.05). The results in subjects who practiced
more than 4 times and 6 h per week were similar to that of all subjects; however,
the improvement in anxiety in the GLQG group was more obvious. There are positive
correlations between QoL and anxiety and depression. CONCLUSIONS: Both GLQG and
physical stretching are beneficial during recovery following breast cancer. GLQC
was more effective in terms of Qol improvements than physical stretching. Both
programs brought improvements in anxiety or depression but had were comparable.
GLQC group had a greater effect on immunological function than physical exercise.
PMID- 28421385
TI - In vitro and in vivo anti-tumor effects of selected platinum(IV) and dinuclear
platinum(II) complexes against lung cancer cells.
AB - In the present study, cytotoxic effects of cisplatin, the most usually used
chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)]
(en = ethylenediamine) and [PtCl4(dach)]) (dach = (+/-)-trans-1,2
diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(MU
pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(MU-4,4'
bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(MU-1,2
bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and
murine lung cancer cells, to determine anti-tumor potential of newly synthesized
platinum-based drugs in the therapy of lung cancer. Results obtained by MTT [3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], Lactate
dehydrogenase and Annexin V/Propidium Iodide assays showed that, among all tested
complexes, [PtCl4(en)] had the highest cytotoxicity against human and murine lung
carcinoma cells in vitro. [PtCl4(en)] showed significantly higher cytotoxicity
then cisplatin in all tested concentrations, mainly by inducing apoptosis in lung
cancer cells. [PtCl4(en)] was well tolerated in vivo. Clinical signs of
[PtCl4(en)]-induced toxicity, such as changes in food, water consumption or body
weight, nephrotoxicity or hepatotoxicity was not observed in [PtCl4(en)]-treated
mice. [PtCl4(en)] managed to increase presence of CD45+ leukocytes, including
F4/80+ macrophages, CD11c+ dendritic cells, CD4+ helper and CD8+ cytotoxic T
cells (CTLs) in the lungs, cytotoxic NK, NKT and CTLs in the spleens of tumor
bearing mice, resulting with reduction of metastatic lesions in the lungs,
indicating its potential to stimulate anti-tumor immune response in vivo. Due to
its anti-tumor cytotoxicity, biocompatibility, and potential for stimulation of
anti-tumor immune response, [PtCl4(en)] may be a good candidate for further
testing in the field of medicinal chemistry.
PMID- 28421386
TI - Technology assessment and cost-effectiveness in orthopedics: how to measure
outcomes and deliver value in a constantly changing healthcare environment.
AB - PURPOSE OF REVIEW: The purpose of this study is to review the basic concepts of
healthcare value, patient outcome measurement, and cost-effectiveness analyses as
they relate to the introduction of new surgical techniques and technologies in
the field of orthopedic surgery. RECENT FINDINGS: An increased focus on financial
stewardship in healthcare has resulted in a plethora of cost-effectiveness and
patient outcome research. Recent research has made great progress in identifying
orthopedic technologies that provide exceptional value and those that do not meet
adequate standards for widespread adoption. As the pace of technological
innovation advances in lockstep with an increased focus on value, orthopedic
surgeons will need to have a working knowledge of value-based healthcare decision
making. Value-based healthcare and cost-effectiveness analyses can aid orthopedic
surgeons in making ethical and fiscally responsible treatment choices for their
patients.
PMID- 28421388
TI - Preferential distribution of nuclear MAPK signal in alpha/beta core neurons
during long-term memory consolidation in Drosophila.
PMID- 28421387
TI - Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins.
AB - There are many factors that can influence the pharmacokinetics (PK) of a mAb or
Fc-fusion molecule with the primary determinant being FcRn-mediated recycling.
Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a
variety of therapeutic antibodies with significantly enhanced half-life or
ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc
fusion protein can have a significant impact on the PK of these molecules. mAb
charge can be important and variants with pI values of 1-2 unit difference are
likely to impact PK with lower pI values being favorable for a longer half-life.
Most mAbs display target mediated drug disposition (TMDD), which can have
significant consequences on the study designs of preclinical and clinical
studies. The PK of mAb can also be influenced by anti-drug antibody (ADA)
response and off-target binding, which require careful consideration during the
discovery stage. mAbs are primarily absorbed through the lymphatics via
convection and can be conveniently administered by the subcutaneous (sc) route in
large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb
can be reasonably estimated using cynomolgus monkey data and allometric scaling
methods.
PMID- 28421389
TI - Preparation and biocompatibility of demineralized bone matrix/sodium alginate
putty.
AB - Demineralized bone matrix (DBM) powder is widely used for bone regeneration due
to its osteoinductivity and osteoconductivity. However, difficulties with
handling, tendency to migrate from graft sites and lack of stability after
surgery sometimes limit the clinical utility of this material. In this work, the
possibility of using sodium alginate (ALG) carrier to deliver DBM powder was
assessed. DBM-ALG putty with the DBM:ALG weight ratio of 5:5, 6:4, 7:3, 8:2 were
prepared, respectively. The properties of the formed composite, including
discrete degree, washout property, pH, equilibrium swelling as well as
cytotoxicity in vivo, were adopted to ascertain the optimal ratio of DBM and ALG.
The discrete diameter increased from 1.25 cm (5:5) to 2.08 cm (8:2) with the
increase of DBM content. There was significant difference between the 8:2 group
and the other groups in discrete diameter. The ratio of DBM had a significant
effect on the swelling value. The pH of composites showed an increase trend with
the DBM ratio's increase, when the ratio reached 7:3, the pH (7.22) was
approximately equal to the body fluid. The proliferation of MC3T3-E1 cells was
inhibited in the 5:5, 6:4 and 7:3 groups, while a slightly increased in the 8:2
group. The DBM-ALG with the optimal ratio of 7:3 was confirmed based on the
results of the above mentioned. The histocompatibility of DBM-ALG (7:3) was
examined using a rat model in which the materials were implanted subcutaneously,
compared with the polyethylene, ALG and DBM. The study in vivo showed DBM-ALG
(7:3) had a lower inflammatory response than DBM, a higher vascularization than
ALG. The osteoinduction of DBM-ALG (7:3) was evaluated by co-culturing with MC3T3
E1 in vitro, compared with the DMEM, ALG and DBM. The results indicated
calcification area in the DBM-ALG group was similar to that in the DBM group,
larger than ALG group and DMEM group. The DBM-ALG (7:3) putty is promising as a
directly injectable graft for repair of bone defect.
PMID- 28421390
TI - Ofatumumab combined with chlorambucil for previously untreated chronic
lymphocytic leukemia: a phase I/II, open-label study in Japan.
AB - Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low
toxicity treatments. Internationally, the standard treatment for such patients is
chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in
Japan. The aim of the present study was to evaluate the safety, efficacy and
pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese
patients with previously untreated CLL who were inappropriate for fludarabine
based therapy. Ten patients were enrolled and treated in this study, all of whom
received at least one dose of the study drugs. The tolerability of the treatment
was confirmed initially with three patients. The overall response rate was 50%,
as determined by the Independent Review Committee (IRC) with computerized
tomography. All patients were alive at follow-up, and only one patient had
progressive disease. The most common treatment-related adverse events (AEs) were
thrombocytopenia (n = 10), neutropenia (n = 9) and rash (n = 6). One grade 3
serious AE related to the study drug occurred (hypoxia). The results indicate
that ofatumumab combined with chlorambucil is an effective treatment for Japanese
CLL patients, with a manageable safety profile.
PMID- 28421391
TI - Epidemiology of Suicide Attempts among Youth Transitioning to Adulthood.
AB - Suicide is the second leading cause of death for older adolescents and young
adults. Although empirical literature has identified important risk factors of
suicidal behavior, it is less understood if changes in risk factors correspond
with changes in suicide risk. To address this knowledge gap, we assessed if there
were different trajectories of suicidal behavior as youth transition into young
adulthood and determined what time-varying risk factors predicted these
trajectories. This study used four waves of data spanning approximately 13 years
from the National Longitudinal Study of Adolescent Health. The sample included
9027 respondents who were 12-18 years old (M = 15.26; SD = 1.76) at Wave 1, 50%
male, 17% Hispanic, and 58% White. The results indicated that 93.6% of the sample
had a low likelihood for suicide attempts across time, 5.1% had an elevated
likelihood of attempting suicide in adolescence but not young adulthood, and 1.3%
had an elevated likelihood of attempting suicide during adolescence and
adulthood. The likelihood of a suicide attempt corresponded with changes on
depression, impulsivity, delinquency, alcohol problems, family and friend suicide
history, and experience with partner violence. Determining how suicide risk
changes as youth transition into young adulthood and what factors predict these
changes can help prevent suicide. Interventions targeting these risk factors
could lead to reductions in suicide attempts.
PMID- 28421393
TI - Modified nomogram for derivation of renal threshold phosphate concentration.
PMID- 28421392
TI - Combination of sacral nerve and tibial nerve stimulation for treatment of bladder
overactivity in pigs.
AB - PURPOSE: Sacral nerve and tibial nerve stimulation have been singly used to treat
overactive bladder (OAB). This study evaluated the effects of both combined
stimulation on treating bladder overactivity in pigs and explored a novel
treatment modality for OAB. METHODS: An implant-driven stimulator of the S3
spinal nerve was implanted in 5 pigs. The contralateral tibial nerve was
stimulated by an external stimulator. Multiple cystometrograms were performed to
determine the effects of single nerve stimulation and combination sacral nerve
stimulation (SNS) and tibial nerve stimulation (TNS) on the micturition reflex by
infusing normal saline (NS) or acetic acid (AA). RESULTS: AA-induced bladder
overactivity significantly reduced bladder capacity (BC) to 16.3 +/- 2.2% of the
NS control level (389.4 +/- 27.68 ml; P < 0.01). When given a single stimulation,
both SNS and TNS significantly increased the BC to 39.2 +/- 1.6% and 34.9 +/-
5.0% of the NS control level (P < 0.01), respectively. Combined SNS and TNS
significantly increased the BC to 50.2 +/- 5.2% of the NS control level (P <
0.01) and induced a superior inhibitory effect than SNS or TNS alone (P < 0.05).
CONCLUSIONS: Combination SNS and TNS induced a superior inhibitory effect on
bladder overactivity in pigs compared to single stimulation and thus could be a
novel treatment modality for OAB.
PMID- 28421394
TI - Waveform Integrity in Atrial Fibrillation: The Forgotten Issue of Cardiac
Electrophysiology.
AB - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with
an increasing prevalence of about 15% in the elderly. Despite other alternatives,
catheter ablation is currently considered as the first-line therapy for the
treatment of AF. This strategy relies on cardiac electrophysiology systems, which
use intracardiac electrograms (EGM) as the basis to determine the cardiac
structures contributing to sustain the arrhythmia. However, the noise-free
acquisition of these recordings is impossible and they are often contaminated by
different perturbations. Although suppression of nuisance signals without
affecting the original EGM pattern is essential for any other later analysis, not
much attention has been paid to this issue, being frequently considered as
trivial. The present work introduces the first thorough study on the significant
fallout that regular filtering, aimed at reducing acquisition noise, provokes on
EGM pattern morphology. This approach has been compared with more refined
denoising strategies. Performance has been assessed both in time and frequency by
well established parameters for EGM characterization. The study comprised
synthesized and real EGMs with unipolar and bipolar recordings. Results reported
that regular filtering altered substantially atrial waveform morphology and was
unable to remove moderate amounts of noise, thus turning time and spectral
characterization of the EGM notably inaccurate. Methods based on Wavelet
transform provided the highest ability to preserve EGM morphology with
improvements between 20 and beyond 40%, to minimize dominant atrial frequency
estimation error with up to 25% reduction, as well as to reduce huge levels of
noise with up to 10 dB better reduction. Consequently, these algorithms are
recommended as a replacement of regular filtering to avoid significant
alterations in the EGMs. This could lead to more accurate and truthful analyses
of atrial activity dynamics aimed at understanding and locating the sources of
AF.
PMID- 28421395
TI - Clinical interpretation of asymptomatic medial collateral ligament injury
observed on magnetic resonance imaging in adolescent baseball players.
AB - PURPOSE: Magnetic resonance imaging (MRI) of medial collateral ligament (MCL)
injury of the elbow was often observed in asymptomatic adolescent baseball
players. We aimed to clarify the clinical interpretation of "asymptomatic MCL
injury observed on MRI" by comparing MRI, ultrasonography (US), and physical
findings. MATERIALS AND METHODS: Sixty-four asymptomatic adolescent baseball
players (mean 11.2 years) were enrolled. An open-type 0.2T MRI was used. MCL
function was evaluated by measuring the opening of the ulnohumeral joint using
US. Physical findings included MCL tenderness, the moving valgus test, and the
Milking test. The correlation between MRI and US, and MRI and physical findings
were analyzed. RESULTS: Thirty-four subjects (53.1%) showed MCL injury by MRI.
The mean laterality of the ulnohumeral joint opening showed no significant
difference (P = 0.16) between the group with (0.29 +/- 1.06 mm) and without (0.08
+/- 0.96 mm) MCL injury on MRI. There was no correlation between MRI and physical
findings except for a weak correlation between subjects with positive Milking
test and MCL injury on MRI (phi coefficient = 0.3, P = 0.02). CONCLUSION:
'Asymptomatic MCL injury on MRI' had little correlation to ligament dysfunction.
It might represent the transition period to MCL thickening called "adaptation."
PMID- 28421396
TI - 11C-methionine PET/CT findings in benign brain disease.
AB - 11C-methionine (MET) is one of the most commonly used positron emission
tomography (PET) tracers for evaluation of malignant brain tumor, with MET-PET
being a sensitive technique for visualization of primary and recurrent malignant
brain tumors. However, previous reports have demonstrated MET uptake in lesions
associated with benign brain diseases. These diseases usually show an increase in
MET uptake similar to that of malignant tumors. This pitfall in MET-PET image
interpretation is important not only for nuclear medicine professionals, but also
for radiologists. In this review, we demonstrate the imaging characteristics of
MET uptake in benign brain disease, and recommend physician interpretation of
imaging findings and disease characteristics for optimal patient management.
Benign uptake must be identified to prevent misdiagnosis and unnecessary surgical
operations.
PMID- 28421397
TI - Comparison between the four-field box and field-in-field techniques for conformal
radiotherapy of the esophagus using dose-volume histograms and normal tissue
complication probabilities.
AB - PURPOSE: We evaluated and compared the performance of the field-in-field (FIF) to
that of the four-field box (4FB) technique regarding dosimetric and
radiobiological parameters for radiotherapy of esophageal carcinoma. MATERIALS
AND METHODS: Twenty patients with esophageal cancer were selected. For each
patient, two treatment plans were created: 4FB and FIF. The parameters compared
included the conformity index (CI), homogeneity index (HI), D mean, D max, tumor
control probability (TCP), V 20Gy and V 30Gy of the heart and lungs, normal
tissue complication probability (NTCP), and monitor units per fraction (MU/fr).
RESULTS: A paired t-test analysis did not show any significant differences (p >
0.05) between the two techniques in terms of the CI and TCP. However, the HI
significantly improved when the FIF was applied. D max of the PTV, lung, and
spinal cord were also significantly better with the FIF. Moreover, the lung V
20Gy as well as the NTCPs of the lung and spinal cord significantly reduced when
the FIF was used, and the MU/fr was significantly decreased. CONCLUSIONS: The FIF
showed evident advantages over 4FB: a more homogeneous dose distribution, lower D
max values, and fewer required MUs, while it also retained PTV dose conformality.
FIF should be considered as a simple technique to use clinically in cases with
esophageal malignancies, especially in clinics with no IMRT.
PMID- 28421398
TI - Supradescemetic voriconazole injection for Candida parapsilosis keratitis.
AB - PURPOSE: To describe a technique for intracorneal application of voriconazole
into the supradescemetic space in a case of deep recalcitrant Candida
parapsilosis keratitis of a penetrating cornea graft. METHODS: A deep
intracorneal incision reaching the center of the corneal infiltrate was created
with a 20-gauge MVR blade. Then, a 27-gauge hydrodissection cannula was inserted
deep into the corneal pocket, and 0.1 ml of voriconazole 0.5 mg/ml was injected
until a bullous detachment of Descemet membrane (DM) covered 1/3 of the graft's
area. DM detachment was documented by anterior segment optical coherence
tomography (AS-OCT). RESULTS: AS-OCT confirmed the creation of a drug depot in
the supradescemetic space, which partially regressed during the following hours;
24 h after the injection, a complete reattachment of DM was documented. After 4
weeks, the stromal infiltrate has cleared completely and no signs of recurrence
were observed 3 months after injection. CONCLUSION: In the present case, the
supradescemetic voriconazole injection led to resolution of a deep recalcitrant
fungal infiltrate. The herein described technique could be tried in similar
cases, where an intrastromal injection is indicated, as it may offer a larger
intracorneal drug depot.
PMID- 28421399
TI - Effect of intravitreal aflibercept (Eylea(r)) on retrobulbar hemodynamics in
patients with neovascular age-related macular degeneration.
AB - PURPOSE: To investigate the short-term effect of single intravitreal aflibercept
injection on retrobulbar blood flow in patients with neovascular age-related
macular degeneration (nAMD). METHODS: Twenty eyes of 20 patients with nAMD
scheduled for single intravitreal aflibercept (Eylea(r)) injection and 20 fellow
eyes (uninjected) were enrolled in this prospective interventional study. The
hemodynamic parameters of the ophthalmic artery (OA), central retinal artery
(CRA) and posterior ciliary artery (PCA) comprising peak systolic velocity (PSV),
end-diastolic velocity (EDV), and resistive index (RI) were measured by using
color Doppler ultrasonography (CDU) in both injected and uninjected fellow eyes
at baseline and 1 week after the injection. RESULTS: The measured first-week
values of PSV and EDV in the CRA, OA and PCA showed a statistically significant
reduction when comparing baseline values in both injected and uninjected fellow
eyes (p = 0.0001). Also, it was found a significant increase in the post
injection RI values of all the CRA, OA, PCA in injected eye and OA in the
uninjected eye (p = 0.0001). There was any significant difference between pre-
and post-injection RI values of the CRA and PCA in the fellow eyes (p = 0.137, p
= 0.736, respectively). CONCLUSION: Single intravitreal administration of
aflibercept alters retrobulbar blood flow velocities (BFVs) in both injected and
uninjected fellow eyes in the short-term period.
PMID- 28421400
TI - A multistage-dialysis microdevice for extraction of cryoprotectants.
AB - In this study, we present a multistage-dialysis microdevice (MDM) for extraction
of cryoprotectants (CPAs) from a CPA-laden cell suspension. We confirmed the
functions of the key designs of the MDM using a fluorescence solution, we
assessed the performance of the MDM by using the MDM to unload glycerin from
glycerin-loaded swine erythrocytes, and we investigated the effects of the cell
suspension flow rate, glycerin concentration, cell density, and membrane pore
size on the clearance efficiency of glycerin (CG), the survival rate of cells
(SC), and the recovery rate of cells (RC). Under the designed conditions, CG, SC,
and RC reached ~60%, ~90%, and ~70%, respectively. In addition, a high flow rate
causes high SC and RC but a low CG. For a low glycerin concentration, CG, SC, and
RC are all high. If a low cell density or a large pore membrane is used, CG is
high, whereas both SC and RC are low. This work provides insight into the
development of microfluidic devices for the inline extraction of cryoprotectants
from a small volume of cryopreserved cells prior to the use of the cells in lab
on-a-chip applications.
PMID- 28421401
TI - Liquid marbles as bioreactors for the study of three-dimensional cell
interactions.
AB - Liquid marble as a bioreactor platform for cell-based studies has received
significant attention, especially for developing 3D cell-based assays. This
platform is particularly suitable for 3D in-vitro modeling of cell-cell
interactions. For the first time, we demonstrated the interaction of olfactory
ensheathing cells (OECs) with nerve debris and meningeal fibroblast using liquid
marbles. As the transplantation of OECs can be used for repairing nerve injury,
degenerating cell debris within the transplantation site can adversely affect the
survival of transplanted OECs. In this paper, we used liquid marbles to mimic the
hostile 3D environment to analyze the functional behavior of the cells and to
form the basis for cell-based therapy. We show that OECs interact with debris and
enhanced cellular aggregation to form a larger 3D spheroidal tissue. However,
these spheroids indicated limitation in biological functions such as the
inability of cells within the spheroids to migrate out and adherence to
neighboring tissue by fusion. The coalescence of two liquid marbles allows for
analyzing the interaction between two distinct cell types and their respective
environment. We created a microenvironment consisting of 3D fibroblast spheroids
and nerve debris and let it interact with OECs. We found that OECs initiate
adherence with nerve debris in this 3D environment. The results suggest that
liquid marbles are ideal for developing bioassays that could substantially
contribute to therapeutic applications. Especially, insights for improving the
survival and adherence of transplanted cells.
PMID- 28421403
TI - Erratum to: CcpNmr AnalysisAssign: a flexible platform for integrated NMR
analysis.
PMID- 28421402
TI - The Effect of Losses Disguised as Wins and Near Misses in Electronic Gaming
Machines: A Systematic Review.
AB - Near misses and losses disguised as wins have been of interest to gambling
researchers and policymakers for many years (e.g., Griffiths in J Gambl Stud
9(2):101-120, 1993). This systematic literature review describes the behavioural,
psychological, and psychobiological effects of near misses and losses disguised
as wins (LDWs) in an effort to evaluate their precise influence on the player and
to highlight areas requiring further investigation. A systematic search for
relevant studies was conducted using Scopus, PubMed, PsycINFO, ProQuest Sociology
databases, and the Gambling Research Exchange Ontario Knowledge Repository. A
total of 51 (from an initial pool of 802) experimental peer-reviewed studies
using human participants were found between 1991 and 2015. The systematic review
revealed that near misses motivate continued play, but have varying effects on
the emotional state or betting behaviour of the player. Near miss events were
also shown to be associated with elevated skin conductance levels and diffuse
activity across the brain, most consistently in areas processing reinforcement
and reward. Re-examination of the studies of near misses events after classifying
the type of game feedback suggested that the effectiveness of near misses is
related to the phenomenology of a near miss itself rather than as a response to
auditory or visual feedback provided by a slot machine. In contrast to near
misses, the presence of LDWs was found to relate to an overestimation of how much
a player is actually winning and was consistently viewed as an exciting event.
The effect of LDWs appears to be driven by the presence of visuals and sounds
most often associated with a true win. Practical implications and directions for
future research are also discussed.
PMID- 28421404
TI - Characterization of ZnO Nanoparticles using Superconducting Tunnel Junction
Cryodetection Mass Spectrometry.
AB - Zinc oxide (ZnO) nanoparticles coated with either n-octylamine (OA) or alpha
amino poly(styrene-co-acrylonitrile) (PSAN) ligands (L) have been analyzed using
laser desorption/ionization and matrix assisted laser desorption/ionization
(MALDI) time-of-flight (TOF) superconducting tunnel junction (STJ) cryodetection
mass spectrometry. STJ cryodetection has the advantage of high m/z detection and
allows for the determination of average molecular weights and dispersities for
500-600 kDa ZnO-L nanoparticles. The ability to detect the relative energies
deposited into the STJs has allowed for investigation of ZnO-L metastable
fragmentation. ZnO-L precursor ions gain enough internal energy during the MALDI
process to undergo metastable fragmentation in the flight tube. These fragments
produced a lower energy peak, which was assigned as ligand-stripped ZnO cores
whereas the individual ligands were at too low of an energy to be observed. From
these STJ energy resolved peaks, the average weight percentage of inorganic
material making up the nanoparticle was determined, where ZnO-OA and ZnO-PSAN
nanoparticles are comprised of ~62% and ~68% wt ZnO, respectively. In one
example, grafting densities were calculated based on the metastable fragmentation
of ligands from the core to be 16 and 1.1 nm-2 for ZnO-OA and ZnO-PSAN,
respectively, and compared with values determined by thermogravimetric analysis
(TGA) and transmission electron microscopy (TEM). Graphical Abstract ?.
PMID- 28421405
TI - Differential Fragmentation of Mobility-Selected Glycans via Ultraviolet
Photodissociation and Ion Mobility-Mass Spectrometry.
AB - The alternative dissociation pathways initiated by ultraviolet photodissociation
(UVPD) compared with collision-induced dissociation (CID) may provide useful
diagnostic fragments for biomolecule identification, including glycans. However,
underivatized glycans do not commonly demonstrate strong UV absorbance, resulting
in low fragmentation yields for UVPD spectra. In contrast to UVPD experiments
that leverage covalent modification of glycans, we detail the capacity of metal
adduction to yield comparatively rich UVPD fragmentation patterns and enhance
separation factors for an isomeric glycan set in a drift tube ion mobility
system. Ion mobility and UVPD-MS spectra for two N-acetyl glycan isomers were
examined, each adducted with sodium or cobalt cations, with the latter providing
fragment yield gains of an order of magnitude versus sodium adducts. Furthermore,
our glycan analysis incorporated front-end ion mobility separation such that the
structural glycan isomers could still be identified even as a mixture and not
simply composite spectra of isomeric standards. Cobalt adduction proved
influential in the glycan separation by yielding an isomer resolution of 0.78
when analyzed simultaneously versus no discernable separation obtained with the
sodium adducts. It is the combined enhancement of both isomeric drift time
separation and isomer distinction with improved UVPD fragment ion yields that
further bolster multivalent metal adduction for advancing glycan IM-MS
experiments. Graphical Abstract ?.
PMID- 28421406
TI - Whole body MRI with qualitative and quantitative analysis of DWI for assessment
of bone marrow involvement in lymphoma.
AB - AIM: Our study aimed to investigate the role of qualitative and quantitative
whole body MRI with DWI for assessment of bone marrow involvement (BMI) in newly
diagnosed lymphoma using FDG PET-CT and bone marrow biopsy (BMB) as reference
standard. MATERIALS AND METHODS: We retrospectively evaluated 56 patients with
newly diagnosed lymphoma (21 Hodgkin's lymphoma and 35 non-Hodgkin's lymphoma)
who underwent random unilateral BMB, FDG PET-CT and Wb-MRI-DWI for initial
staging. In a patient-based analysis, results of Wb-MRI-DWI were compared with
FDG PET-CT and BMB. For quantitative analysis, mean ADC values of posterior iliac
crest were correlated with BMI and bone marrow cellularity. RESULTS: WB-MR-DWI
obtained excellent concordance with FDG PET-CT both in HL (k = 1.000; 95% CI
1.000-1.000) and in DLBCL (k = 1.000; 95% CI 1.000-1.000). In other NHL, WB-MRI
DWI obtained a good correlation with BMB (k = 0.611; 95% CI 0.295-0.927) while
FDG PET-CT had poor concordance (k = 0.067; 95% CI 0.372-0.505). WB-MR-DWI has no
false negative errors but 4 false positive results consisting in focal lesions
consensually reported by FDG PET-CT and resolved after therapy. No significant
correlation between ADC mean value and BMI was found (p = 0.0586). CONCLUSION:
Our data suggest that Wb-MRI-DWI is a valid technique for BMI assessment in
lymphoma patients, thanks to its excellent concordance with FDG PET-CT and good
concordance with BMB (superior than FDG PET-CT). If further investigations will
confirm our results on larger patient groups, it could become a useful tool in
the clinical workup.
PMID- 28421407
TI - Treatment of non-healing post-surgical fistula: a challenge for interventional
radiologist.
PMID- 28421408
TI - Pharmacological and Non-pharmacological Treatment for Decompensated Heart
Failure: What Is New?
AB - PURPOSE OF THE REVIEW: Acute heart failure (AHF) is a life-threatening clinical
condition that requires prompt medical attention. The aim of the current review
is to summarise the results of recent clinical trials conducted in patients with
AHF. RECENT FINDINGS: Several novel compounds have apparently beneficial acute
effects on cardiovascular haemodynamics and patients' symptoms, but their
administration has not yet translated into improved survival and has been
deleterious in some cases. The management of patients with AHF is challenging and
reflects the heterogeneity of patient's presentation, the complexity and severity
of a multi-organ syndrome, and the limited therapeutic options, usually
restricted to a combination of diuretics and vasodilators. Ongoing trials of
novel treatments may provide evidence of an effect on outcomes.
PMID- 28421409
TI - Six-Minute Walk Test for Assessing Physical Functional Capacity in Chronic Heart
Failure.
AB - PURPOSE OF THE REVIEW: The six-minute walk test (6MWT) is a submaximal exercise
test for evaluating physical functional capacity. This review aims to report the
research on the use of the 6MWT in chronic heart failure (CHF) that has been
published in the past 5 years. RECENT FINDINGS: The 6MWT distance does not
accurately reflect peak VO2. Minimal clinically important difference in the 6MWT
distance, and additional measurements, such as heart rate recovery, can assist in
the interpretation of the 6MWT distance, so management decisions can be made.
Incorporating mobile apps and information technology in measuring the 6MWT
distance extends the usefulness of this simple walk test and improve remote
monitoring of patients with CHF. The 6MWT is a useful tool in CHF programs.
However, interpretation of the 6MWT distance must be with caution. With the
advancement in technology, the 6MWT has the potential to facilitate the
monitoring of people living in rural and remote areas.
PMID- 28421410
TI - Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and
Preliminary In Vitro and In Silico DMPK Assessment.
AB - The antiparasitic activity and preliminary in vitro and in silico drug metabolism
and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1-6),
isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is
reported. The study was prompted by the observation that two of the compounds (1
and 2) exhibited varying levels of antiparasitic activity on Plasmodium
falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania
donovani. The in silico method employed a total of 46 descriptors, calculated
using Schrodinger QikProp software. 18 of these molecular descriptors that are
often used to predict DMPK profiles of drug-like molecules have been selected for
discussion. In vitro experimental assessment of metabolic stability made use of
human liver microsomes, which was used to correlate theoretical predictions with
experimental findings. Overall, the test compounds have been found to have
acceptable physicochemical properties and fall within the ranges associated with
"drug-like" molecules. Moreover, the compounds exhibited minimal degradation in
incubations with human liver microsomes. Although some of these compounds have
been reported previously (1, 2, 4 and 5), this is the first report on their
antiparasitic activities, as well as assessment of their DMPK profiles. These
results have therefore provided a window for further development of this novel
class of sesquiterpene molecules as potential antiparasitic drugs.
PMID- 28421411
TI - Seleno-short-chain chitosan induces apoptosis in human non-small-cell lung cancer
A549 cells through ROS-mediated mitochondrial pathway.
AB - Seleno-short-chain chitosan (SSCC) is a synthesized chitosan derivative. In this
study, antitumor activity and underlying mechanism of SSCC on human non-small
cell lung cancer A549 cells were investigated in vitro. The MTT assay showed that
SSCC could inhibit cell viability in a dose- and time-dependent manner, and 200
MUg/ml SSCC exhibited significantly toxic effects on A549 cells. The cell cycle
assay showed that SSCC triggered S phase cell cycle arrest in a dose- and time
dependent manner, which was related to a downregulation of S phase associated
cyclin A. The DAPI staining and Annexin V-FITC/PI double staining identified that
the SSCC could induce A549 cells apoptosis. Further studies found that SSCC led
to the generation of reactive oxygen species (ROS) and the disruption of
mitochondrial membrane potential (MMP) by DCFH-DA and Rhodamin 123 staining,
respectively. Meanwhile, free radical scavengers N-acetyl-L-cysteine (NAC)
pretreatment confirmed that SSCC-induced A549 cells apoptosis was associated with
ROS generation. Furthermore, real-time PCR and western blot assay showed that
SSCC up-regulated Bax and down-regulated Bcl-2, subsequently incited the release
of cytochrome c from mitochondria to cytoplasm, activated the increase of cleaved
caspase 3 and finally induced A549 cells apoptosis in vitro. In general, the
present study demonstrated that SSCC induced A549 cells apoptosis via ROS
mediated mitochondrial apoptosis pathway.
PMID- 28421412
TI - Bioactive compounds and antioxidant activity exhibit high intraspecific
variability in Pleurotus ostreatus mushrooms and correlate well with cultivation
performance parameters.
AB - Experimental data related with oyster mushroom production and nutritional
properties usually derive from the examination of only one strain, and hence
their representativeness/usefulness is questionable. This work aims at assessing
intraspecific variability in Pleurotus ostreatus by studying 16 strains, under
the same conditions, in respect to essential cultivation and mushroom quality
aspects, and by defining the impact of intrinsic/genetic factors on such
parameters. Hence, mushroom yield, earliness, crop length, biological efficiency,
productivity, and their content in selected macro and microconstituents (e.g.
fatty acids, sterols, individual phenolic compounds, terpenic acids, glucans) as
well as their antioxidant properties (i.e., antiradical activity, ferric reducing
potential, inhibition of serum oxidation) were assayed. The effect of
intrinsic/genetic factors was evident, especially as regards earliness, yield of
each production flush and mushroom weight, whereas biological efficiency was not
particularly influenced by the cultivated strain. Moreover, phenolics, ergosterol
and antiradical activity demonstrated significant variability among strains in
contrast to what was observed for fatty acids, beta-glucans and ferric reducing
potential. The observed heterogeneity reveals the limitations of using a low
number of strains for evaluating mushroom production and/or their content in
bioactive compounds, and as evidenced, it is valuable for breeding and commercial
purposes.
PMID- 28421413
TI - Substrate-Induced Conformational Changes of the Tyrocidine Synthetase 1
Adenylation Domain Probed by Intrinsic Trp Fluorescence.
AB - Nonribosomal peptide synthetases (NRPS) are multifunctional proteins that
catalyze the synthesis of the peptide products with enormous biological
potential. The process of biosynthesis starts with the adenylation (A) domain,
which during the catalytic cycle undergoes extensive structural rearrangements.
In this paper, we present the first study of the tyrocidine synthetase 1 A-domain
(TycA-A) fluorescence properties. The TycA-A protein contains five potentially
fluorescent Trp residues at positions 227, 301, 323, 376 and 406. The
contribution of each Trp to the TycA-A emission was determined using protein
variants bearing single Trp to Phe substitutions. The accessibility of the Trp
side chains during adenylation showed that only W227 is affected by substrate
binding. The protein variant containing solely fluorescent W227 residue was
constructed and further used as a probe to explore the binding effect of
different non-cognate amino acid substrates. The results indicate a different
accessibility of W227 residue in the presence of non-cognate amino acids, which
might offer an explanation for the higher aminoacyl-adenenylate leakage. Overall,
our results suggest that intrinsic tryptophan fluorescence could be used as a
method to probe the effect of substrate binding on the local structure in NRPS
adenylation domains.
PMID- 28421414
TI - Polyclonal Antibodies in Microplates to Predict the Maximum Adsorption Activities
of Enzyme/Mutants from Cell Lysates.
AB - With microplate-immobilized polyclonal antibodies against a starting enzyme or
its active mutant bearing consistent accessible epitopes, the maximum activity of
an adsorbed enzyme/mutant (Vs) was predicted for comparison to recognize weakly
positive mutants. Rabbit antisera against Escherichia coli alkaline phosphatase
(ECAP) were fractionated with 33% ammonium sulfate to yield crude polyclonal
antibodies for conventional immobilization in 96-well microplates. The response
curve of the activities of ECAP/mutant adsorbed by the immobilized polyclonal
antibodies to protein quantities from a cell lysate was fit to an approximation
model to predict Vs. With 0.4 MUg crude polyclonal antibody for immobilization,
Vs was consistent for ECAP in cell lysates bearing fourfold differences in its
apparent specific activities when its abundance was greater than 0.9%. The ratio
of Vs of the mutant R168K to that of ECAP was 1.5 +/- 0.1 (n = 2), consistent
with that of their specific activities after affinity purification.
Unfortunately, the prediction of Vs with polyclonal antibodies that saturated
microplate wells was ineffective to Pseudomonas aeruginosa arylsulfatase bearing
less than 2% specific activity of ECAP. Therefore, with microplate-immobilized
polyclonal antibodies to adsorb enzyme/mutants from cell lysates, high-throughput
prediction of Vs was practical to recognize weakly-positive mutants of starting
enzymes bearing fairly-high activities.
PMID- 28421415
TI - A Tyrosine Residue Along with a Glutamic Acid of the Omega-Like Loop Governs the
Beta-Lactamase Activity of MSMEG_4455 in Mycobacterium smegmatis.
AB - Mycobacterial beta-lactamases are involved in exerting beta-lactam resistance,
though many of these proteins remain uncharacterized. Here, we have characterized
MSMEG_4455 of Mycobacterium smegmatis as a beta-lactamase using molecular,
biochemical and mutational techniques. To elucidate its nature in vivo and in
vitro, and to predict its structure-function relationship in silico analysis is
done. The MSMEG_4455 is cloned and expressed ectopically in a beta-lactamase
deficient Escherichia coli mutant to establish the in vivo beta-lactamase like
nature via minimum inhibitory concentration (MIC) determination. Likewise the in
vivo results, purified soluble form of MSMEG_4455 showed beta-lactam hydrolysis
pattern similar to group 2a penicillinase. In silico analyses of MSMEG_4455
reveal glutamic acid (E)193 and tyrosine (Y)194 of omega-like loop might have
importance in strengthening hydrogen bond network around the active-site, though
involvement of tyrosine is rare for beta-lactamase activity. Accordingly, these
residues are mutated to alanine (A) and phenylalanine (F), respectively. The
mutated proteins have partially lost their ability to exert beta-lactamase
activity both in vivo and in vitro. The Y194F mutation had more prominent effect
on the enzymatic activity. Therefore, we infer that Y194 is the key for beta
lactamase activity of MSMEG_4455.
PMID- 28421416
TI - Emergence of CTNNB1 mutation at acquired resistance to KIT inhibitor in
metastatic melanoma.
AB - PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients
with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs
rapidly in the majority of patients. The mechanisms of acquired resistance to
imatinib in melanoma remain unclear. METHODS: We analyzed biopsy samples from
paired baseline and post-treatment tumor lesions in one patient with KIT-mutated
melanoma who had had an initial objective tumor regression in response to
imatinib treatment followed by disease progression 8 months later. RESULTS:
Targeted deep sequencing from post-treatment biopsy samples detected an
additional mutation in CTNNB1 (S33C) with original KIT L576P mutation. We
examined the functional role of the additional CTNNB1 S33C mutation in resistance
to imatinib indirectly using the Ba/F3 cell model. Ba/F3 cell lines transfected
with both the L576P KIT mutation and the CTNNB1 S33C mutation demonstrated no
growth inhibition despite imatinib treatment, whereas growth inhibition was
observed in the Ba/F3 cell line transfected with the L576 KIT mutation alone.
CONCLUSIONS: We report the first identification of the emergence of a CTNNB1
mutation that can confer acquired resistance to imatinib. Further investigation
into the causes of acquired resistance to imatinib will be essential to improve
the prognosis for patients with KIT-mutated melanoma.
PMID- 28421417
TI - Estimation of QT interval prolongation through model-averaging.
AB - The current method to analyze concentration-QT interval data, which is based on
predictions conditional on a best model, fails to take into account the
uncertainty of the model. Previous studies have suggested that failure to take
into account model uncertainty using a best model approach can result in
confidence intervals that are overly optimistic and may be too narrow.
Theoretically, more realistic estimates are obtained using model-averaging where
the overall point estimate and confidence interval are a weighted-average from a
set of candidate models, the weights of which are equal to each model's Akaike
weight. Monte Carlo simulation was used to determine the degree of narrowness in
the confidence interval for the degree of QT prolongation under a single
ascending dose and thorough QT trial design. Results showed that model averaging
performed as well as the best model approach under most conditions with no
numeric advantage to using a model averaging approach. No difference was observed
in the coverage of the confidence intervals when the best model and model
averaging was done by AIC, AICc, or BIC, although in certain circumstances the
coverage of the confidence interval themselves tended to be too narrow when using
BIC. Modelers can continue to use the best model approach for concentration-QT
modeling with confidence, although model averaging may offer more face validity,
may be of value in cases where there is uncertainty or misspecification in the
best model, and be more palatable to a non-technical reviewer than the best model
approach.
PMID- 28421418
TI - Lower urinary tract symptoms (LUTS) in males with type 2 diabetes recently
treated with SGLT2 inhibitors-overlooked and overwhelming? A retrospective case
series.
PMID- 28421419
TI - Phylogenetic analysis of avian infectious bronchitis virus isolates from Morocco:
a retrospective study (1983 to 2014).
PMID- 28421420
TI - The Future of Targeting FLT3 Activation in AML.
AB - Internal tandem duplications (ITD) and tyrosine-kinase domain (TKD) mutations of
the FMS-like tyrosine-kinase 3 (FLT3) can be found in up to one third of patients
with acute myeloid leukemia (AML) and confer a poor prognosis. First discovered
20 years ago, these mutations were identified as viable therapeutic targets, and
FLT3 tyrosine-kinase inhibitors (TKIs) have been in development for the last
decade with steadily increasing potency. However, FLT3-mutated AML often acquires
resistance to the growing armamentarium of FLT3 inhibitors through a variety of
mechanisms. In this review, we discuss the distinct clinical phenotype of FLT3
mutated AML, historically and currently available therapeutics, mechanisms of
resistance, ongoing trials, and future outlook at treatment strategies.
PMID- 28421421
TI - Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy.
AB - PURPOSE: In pituitary apoplexy (PA), there are preliminary reports on the
appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise
uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of
this study was to evaluate the incidence and clinical significance of SSMT in
patients with PA and a control group of surgically treated non-functioning
pituitary adenomas (NFPAs). METHODS: Retrospective review of clinical and imaging
variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured
on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was
defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic
regression was used to identify factors associated with SSMT. RESULTS: There were
50 NFPA and 47 PA patients. PA patients were managed conservatively (N = 11) or
surgically (N = 36). The median sphenoid sinus mucosal thickness was greater in
the PA than NFPA groups (2.0 vs. 0.5 mm; p < 0.001). In multivariate analysis of
both the PA and NFPA groups, the presence of PA was the only factor associated
with SSMT (OR 0.043, 95% CI 0.012-0.16; p < 0.001). In multivariate analysis of
the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR
0.12, 95% CI 0.026-0.54; p = 0.006) and a more severe grade of apoplexy (OR 7.29,
95% CI 1.10-48.40; p = 0.04), were associated with SSMT. CONCLUSION: The
incidence of SSMT is higher in patients with PA, especially during the acute
phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory
and/or infective changes.
PMID- 28421422
TI - Hepatitis C Virus-Genotype 3: Update on Current and Emergent Therapeutic
Interventions.
AB - PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved
the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent
infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or
hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge
compared with other genotypes. The dependence of the HCV life cycle on host lipid
metabolism suggests the possible utility of targeting host cellular factors for
combination anti-HCV therapy. We discuss current and emergent DAA regimens for
HCV-GT3 treatment. We then summarize recent research findings on the reliance of
HCV entry, replication, and virion assembly on host lipid metabolism. RECENT
FINDINGS: Current HCV treatment guidelines recommend the use of daclatasvir plus
sofosbuvir (DCV/SOF) or sofosbuvir plus velpatasvir (SOF/VEL) for the management
of GT3 based upon clinical efficacy [>=88% overall sustained virological response
(SVR)] and tolerability. Potential future DAA options, such as SOF/VEL co
formulated with GS-9857, also look promising in treating cirrhotic GT3 patients.
However, HCV resistance to DAAs will likely continue to impact the therapeutic
efficacy of interferon-free treatment regimens. Disruption of HCV entry by
targeting required host cellular receptors shows potential in minimizing HCV
resistance and broadening therapeutic options for certain subpopulations of GT3
patients. The use of cholesterol biosynthesis and transport inhibitors may also
improve health outcomes for GT3 patients when used synergistically with DAAs. Due
to the morbidity and mortality associated with HCV-GT3 infection compared to
other genotypes, efforts should be made to address current limitations in the
therapeutic prevention and management of HCV-GT3 infection.
PMID- 28421424
TI - Erratum to: Replacement of Marine Fish Oil with de novo Omega-3 Oils from
Transgenic Camelina sativa in Feeds for Gilthead Sea Bream (Sparus aurata L.).
PMID- 28421423
TI - The Effects of Direct-fed Microbial Supplementation, as an Alternative to
Antibiotics, on Growth Performance, Intestinal Immune Status, and Epithelial
Barrier Gene Expression in Broiler Chickens.
AB - The objective of this study was to investigate the effects of Bacillus subtilis
based probiotic supplementation in broiler chicken diets on growth performance,
feed efficiency, intestinal cytokine, and tight junction (TJ) protein mRNA
expression. Zero-day-old broiler chicks (n = 140) were randomly assigned to one
of five dietary treatments: basal diet (CON); basal diet supplemented with either
antibiotic bacitracin methylene disalicylate (BMD); or probiotics, namely, B.
subtilis strain 1781 (PB1), a combination of B. subtilis strain 1104 + strain 747
(PB2), or B. subtilis strain 1781 + strain 747 (PB3). Body weight and feed intake
were measured at 14 days of age, and the feed conversion ratio (FCR) was
calculated. At 14 days of age, ileal samples were collected and used for
intestinal cytokine, TJ protein, and mucin gene expression analysis using qRT
PCR. The chickens supplemented with antibiotic (BMD) and B. subtilis strain 1781
alone (PB1) had significantly higher body weights compared to controls of the
same age. Dietary supplementation with antibiotic (BMD) or probiotics (PB1, PB2,
PB3) significantly improved the feed efficiency as evidenced by decreased FCR
compared to controls. No differences were observed in the expression of IL1beta,
IL17F, IFNgamma, and MUC2 gene among the different treatment groups. However,
elevated expression of IL6 (BMD, PB1, PB2), IL8 (PB2), and TNFSF15 (PB1, PB2,
PB3) compared to controls was observed in the ileum. IL2 and IL10 expression was
upregulated in chicks in the PB2 and PB3 groups, and IL4 was elevated in the PB1
group. IL13 was elevated in all probiotic-fed groups (PB1, PB2, PB3). Probiotic
supplementation was also shown to significantly increase the expression of TJ
proteins JAM2, ZO1 (PB2, PB3), and occludin (PB1, PB2). Taken together, B.
subtilis supplementation altered intestinal immune activity and influenced gut
barrier integrity through increased tight junction gene expression.
PMID- 28421425
TI - The Role of Alaska's Tribal Health Workers in Supporting Families.
AB - Alaska's Community Health Aides/Practitioners (CHA/Ps) are often the sole medical
workers in their communities in rural Alaska, and are instrumental in providing
healthcare services and education to otherwise underserved individuals. This
qualitative study explored how CHA/Ps support healthy families. Six CHA/Ps from
two rural communities in western Alaska were interviewed about their scope of
practice, interactions with mothers, infants, families, and teens, relationship
to other medical providers, and perceptions of their work. Using grounded theory,
verbatim notes were analyzed in Dedoose software and coded by thematic and
structural components. Interviewed CHA/Ps shared how the CHA/P program is a
culturally relevant way to deliver healthcare, and talked about the challenges of
the work, rewards, and suggestions for improvement. CHA/Ps described their unique
role as the on-the-ground health and wellness resource in their communities, and
talked about consulting with other medical professionals to provide better care
for individuals in rural Alaska. CHA/Ps described that they provided prenatal
care, patient education during pregnancy, emergency delivery services when
necessary, well-child visits, and outreach to teens to give fluoride rinses,
vaccinations, and education about issues such as sexual health and drugs/alcohol.
CHA/Ps also talked about patient education as a primary responsibility, which
also reduced patient load and prevented burn-out. The CHA/P program is a
comprehensive and innovative approach to providing healthcare education and
services that promotes healthy communities, including positive parent-infant
interactions, child wellness, and teen decision-making. The program is a
healthcare delivery model translatable to other tribal and limited-resource
contexts.
PMID- 28421426
TI - Decision-Making Preferences Among Older Hispanics Participating in a Colorectal
Cancer (CRC) Screening Program.
AB - Shared decision making has been shown to improve patients experience and
satisfaction with care within the health care setting but it is not clear that
all patients want to play an active role in health care decisions. The aim of
this study is to describe general decision control preferences among a
predominantly Spanish speaking Hispanic population. This is a cross-sectional
study using the Control Preference Scale to assess decision-making preference. A
total of 780 subjects completed the survey (response rate 89.9%). The majority
preferred a collaborative role (53.3%) compared to a passive (26.4%) or active
role (20.3%). We observed that individuals who were married or living with a
partner were more likely to prefer an active or collaborative role than their
unmarried counterparts (RRR 1.78 P value 0.017; RRR 1.56 p value 0.012). Less
acculturated individuals (i.e. more Spanish speaking at home were less likely to
prefer an active vs. passive role) (RRR 0.296, P value 0.029). Our predominantly
Spanish speaking Hispanic population showed a preference for collaborative versus
active or passive roles. There are several demographic factors that are
associated with this preference but it remains important to determine
individual's preference for decision making in health care settings.
PMID- 28421427
TI - Community Violence Exposure and Risk Taking Behaviors Among Black Emerging
Adults: A Systematic Review.
AB - Black emerging adults ages 18-29, particularly those residing in predominantly
black urban communities, are at risk for community violence exposure (CVE). This
potentially traumatic event may induce traumatic stress reactions for black
emerging adults that contribute to their engagement in violence perpetration,
substance use and/or sexual risk-taking behaviors as a way to cope with their
experiences. To address these identified concerns and make recommendations for
future research, this article identifies and synthesizes results from studies
that have examined CVE and its association with violence perpetration, substance
use, and sexual risk-taking behaviors among black emerging adults. We use the
term "black" throughout the article to refer to a socially constructed racial
group or identity and recognize that this group, like all other racial groups in
the United States, are ethnically heterogeneous. A systematic review of the
literature was conducted to identify studies that (1) included a measure of CVE
(2) included a measure of violence perpetration, substance use, or sexual risk
taking behaviors, and (3) included primarily black emerging adults. Results
showed CVE rates as high as 83% for black emerging adults. CVE was significantly
associated with substance use, but findings on the association of CVE with
violence perpetration and sexual risk-taking behaviors were mixed. Also, there
was a lack of consistency in measures used to assess CVE, suggesting that future
research should seek to identify "gold standard" measures and consider whether
they have been examined with black emerging adults or similar populations and
whether they capture the experiences of this unique population. Furthermore,
studies investigating factors that might moderate and/or mediate the relationship
between CVE, violence perpetration, substance use, and sexual risk-taking
behaviors among black emerging adults are warranted.
PMID- 28421428
TI - How Has CDER Prepared for the Nano Revolution? A Review of Risk Assessment,
Regulatory Research, and Guidance Activities.
AB - The Nanotechnology Risk Assessment Working Group in the Center for Drug
Evaluation and Research (CDER) within the United States Food and Drug
Administration (FDA) was established to assess the potential impact of
nanotechnology on drug products. One of the working group's major initiatives has
been to conduct a comprehensive risk management exercise regarding the potential
impact of nanomaterial pharmaceutical ingredients and excipients on drug product
quality, safety, and efficacy. This exercise concluded that current review
practices and regulatory guidance are capable of detecting and managing the
potential risks to quality, safety, and efficacy when a drug product incorporates
a nanomaterial. However, three risk management areas were identified for
continued focus during the review of drug products containing nanomaterials: (1)
the understanding of how to perform the characterization of nanomaterial
properties and the analytical methods used for this characterization, (2) the
adequacy of in vitro tests to evaluate drug product performance for drug products
containing nanomaterials, and (3) the understanding of properties arising from
nanomaterials that may result in different toxicity and biodistribution profiles
for drug products containing nanomaterials. CDER continues to actively track the
incorporation of nanomaterials in drug products and the methodologies used to
characterize them, in order to continuously improve the readiness of our science-
and risk-based review approaches. In parallel to the risk management exercise,
CDER has also been supporting regulatory research in the area of nanotechnology,
specifically focused on characterization, safety, and equivalence (between
reference and new product) considerations. This article provides a comprehensive
summary of regulatory and research efforts supported by CDER in the area of drug
products containing nanomaterials and other activities supporting the development
of this emerging technology.
PMID- 28421429
TI - Reslizumab in Eosinophilic Asthma: A Review.
AB - Reslizumab (Cinqaero(r); Cinqair(r)) is a humanized monoclonal antibody against
interleukin-5 (IL-5), a cytokine mediator of eosinophilic airway inflammation.
Reslizumab is indicated as an add-on treatment for severe eosinophilic asthma in
adults, on the basis of data from the BREATH phase III clinical trial programme.
In three double-blind BREATH studies of up to 52 weeks' duration, adding
intravenous reslizumab (3 mg/kg, once every 4 weeks) to the current asthma
therapy of patients (aged 12-75 years) with eosinophilic asthma inadequately
controlled with inhaled corticosteroids resulted in significant reductions in
clinical asthma exacerbation frequency and significant improvements in lung
function, asthma control and health-related quality of life relative to adding
placebo. Pooled data from the two trials of 52 weeks' duration indicated similar
benefits with reslizumab across various patient subgroups, including patients
with severe eosinophilic asthma. Reslizumab was generally well tolerated, with
very few recipients experiencing severe or serious treatment-related adverse
events. Moreover, in an open-label extension study, continued use of reslizumab
for up to 2 years was associated with durable lung function benefit, without any
new tolerability concerns. Thus, intravenous reslizumab extends the valuable add
on treatment options for adults with severe eosinophilic asthma inadequately
controlled with standard therapies.
PMID- 28421430
TI - Imbalance of morphofunctional responses of Jurkat T lymphoblasts at short-term
culturing with relief zinc- or copper-containing calcium phosphate coating on
titanium.
AB - Morphofunctional response of Jurkat T cells that were cultured for 24 h on
substrates prepared from commercially pure titanium with relief microarc
bilateral calcium phosphate coating containing copper or zinc was studied.
Changes in the concentration of essential trace elements contained in this
coating can cause significant imbalance of molecular processes of
differentiation, secretion, apoptosis, and necrosis and reduce tumor cell
survival.
PMID- 28421431
TI - Detection of autoantibodies to potentially amyloidogenic protein, gamma
synuclein, in the serum of patients with amyotrophic lateral sclerosis and
cerebral circulatory disorders.
AB - In this study, we analyzed serum for the presence of antibodies to gamma
synuclein in patients with amyotrophic lateral sclerosis (ALS) compared to the
control group of patients with other neurological diseases and healthy control
donors. As a result, antibodies against gamma-synuclein are not an ALS-specific
feature and have been identified in patients with ALS as well as in the control
group patients. Patients with the impaired cerebral circulation showed increased
incidence of autoantibodies to gamma-synuclein, yet the difference lacks
statistical representativeness due to limited sample size.
PMID- 28421432
TI - Regeneration of jejunal wall defect using an implant based on silk fibroin
fibers.
AB - Regenerative properties of fibroin implant vitalized with allogeneic bone marrow
cells were assessed. The study was performed using the experimental model of rat
jejunum wall damage. Three weeks after surgery, we observed recovery of all
layers of the jejunum wall at the site of injury and complete degradation of the
implant material.
PMID- 28421433
TI - Modification of the catalytic subunit of plasma fibrin-stabilizing factor under
induced oxidation.
AB - For the first time, by using mass-spectrometry method, the oxidation-mediated
modification of the catalytic FXIII-A subunit of plasma fibrin-stabilizing
factor, pFXIII, has been studied. The oxidative sites were identified to belong
to all structural elements of the catalytic subunit: the beta-sandwich (Tyr104,
Tyr117, and Cys153), the catalytic core domain (Met160, Trp165, Met266, Cys328,
Asp352, Pro387, Arg409, Cys410, Tyr442, Met475, Met476, Tyr482, and Met500), the
beta-barrel 1 (Met596), and the beta-barrel 2 (Met647, Pro676, Trp692, Cys696,
and Met710), which correspond to 3.9%, 1.11%, 0.7%, and 3.2%, respectively, of
oxidative modifications as compared to the detectable amounts of amino acid
residues in each of the structural domains. Lack of information on some parts of
the molecule may be associated with the spatial unavailability of residues,
complicating analysis of the molecule. The absence of oxidative sites localized
within crucial areas of the structural domains may be brought about by both the
spatial inaccessibility of the oxidant to amino acid residues in the zymogen and
the screening effect of the regulatory FXIII-B subunit.
PMID- 28421434
TI - Estimation of fluorescence lifetime of lipofuscin fluorophores contained in
lipofuscin granules of retinal pigment epithelium of human cadaver eyes without
signs of pathology.
AB - The fluorescence lifetimes of lipofuscin fluorophores contained in chloroform
extracts from retinal pigment epithelium (RPE) of human cadaver eyes without
signs of pathology were evaluated by single photon counting. The comparison of
fluorescence lifetimes of N-retinylidene-N-retinylethanolamine (A2E) and its
photooxidation and photodegradation products has been carried out. It was shown
that the contribution of A2E to the total fluorescence of chloroform extract from
lipofuscin granules is not major. The results are important for the improvement
of noninvasive diagnostic method of degenerative diseases of the retina and RPE
fundus autofluorescence (FAF).
PMID- 28421435
TI - Seasonal changes in proteolytic activity of calpains in striated muscles of long
tailed ground squirrel Spermophilus undulatus.
AB - Seasonal changes in proteolytic activity and content of calpains in striated
muscles of the longtailed ground squirrel Spermophilus undulatus were studied by
casein zymography and Western blotting analysis. The results testify to
hyperactivation of calpain proteases in the skeletal muscles of awakened animals
during the "winter" activity. The observed changes are discussed in the context
of adaptation of skeletal muscles of long-tailed ground squirrels to hibernation.
PMID- 28421436
TI - Molecular mechanisms of synthesis of noradrenaline as an inducer of development
in the adrenal glands of rats in ontogenesis.
AB - The level of gene expression and the protein content of tyrosine hydroxylase and
dopamine beta-hydroxylase were determined. In the perinatal period of rats, when
noradrenaline functions as a morphogenetic factor, the level of gene expression
of these enzymes increased and the content of protein products of these genes was
almost unchanged, indicating the difference in the regulatory mechanisms of their
transcription and translation.
PMID- 28421437
TI - Bioluminescent assay for toxicological assessment of nanomaterials.
AB - A new method for assessing biotoxicity of nanomaterials, based on the use of
soluble bioluminescent coupled enzyme system NAD(P)?H:FMN oxidoreductase and
luciferase, is proposed. The results of this study indicate a significant adverse
biological effect exerted by nanoparticles at the molecular level. It was found
that the most toxic nanoparticles the nanoparticles are based on copper and
copper oxide, as well as single-walled carbon nanotubes and multi-walled carbon
nanofibers, which are referred to hazard class II.
PMID- 28421438
TI - Analysis of fatty acid composition revealed differences in the diets of tadpoles
of two amphibian species.
AB - The study of the composition of fatty acid markers of tadpoles of cohabiting
amphibian species for the first time revealed differences in their diets: the
moor frog Rana arvalis prefers bacteria not associated with plant detritus,
whereas the diet of the common spadefoot Pelobates fuscus is based on
cyanobacteria, green algae, diatoms, and possibly higher plants. Major
differences in the fatty acid composition are determined by the difference in the
percentage of eicosapentaenoic and myristic acids.
PMID- 28421439
TI - Sigma-1 receptor antagonist haloperidol attenuates Ca2+ responses induced by
glutoxim and molixan in macrophages.
AB - Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1
receptor antagonist, antipsychotic haloperidol, significantly inhibits glutoxim-
and molixan-induced Ca2+-response in peritoneal macrophages. These results
indicate possible involvement of sigma-1 receptors in the signal cascade induced
by glutoxim or molixan and leading to intracellular Ca2+ concentration increase
in macrophages.
PMID- 28421440
TI - Transcriptomic changes in human umbilical cord blood endothelial cells under
simulated microgravity.
AB - Microarray analysis of cultured endothelial cells was performed 24 h after
simulated microgravity. A significant change in the expression of 177 genes that
can be classified into several functional clusters was detected. Among the genes
with overexpression, clusters of cell response to external stimuli and regulation
of cell motility and proliferation can be reliably distinguished. Among down
regulated genes, clusters of transcription factors with the "zinc fingers" domain
and factors involved in the regulation of morphogenesis and angiogenesis were
distinguished. The overlapping of signaling pathways involved in
mechanotransduction and inflammatory changes is discussed.
PMID- 28421441
TI - N-methyl serotonin analogues from the Bufo bufo toad venom interact efficiently
with the alpha7 nicotinic acetylcholine receptors.
AB - Two low-molecular-weight compounds were isolated from the parotid gland secret of
the toad Bufo bufo, which by absorption spectra and HPLC-MS/MS chromatography
data correspond to di- and trimethyl derivatives of serotonin (5
hydorxytryptamine): bufotenine (confirmed by counter synthesis) and bufotenidine
(5-HTQ). In experiments on competitive radioligand binding, these compounds
showed a higher affinity and selectivity for neuronal alpha7 nicotinic
acetylcholine receptors compared with the muscular cholinergic receptors. The
most efficient compound in terms of binding value was bufotenine, the efficiency
of 5-HTQ was an order of magnitude lower, and the minimal activity was exhibited
by serotonin.
PMID- 28421442
TI - Silica-containing inclusions in the cytoplasm of diatom Synedra acus.
AB - Cells of the araphid pennate diatom Synedra acus subsp. radians contain large
inclusion (1-15 MUm) storing silica, as revealed by transmission electron
microscopy and EDX-analysis. The size of the inclusions increases with the time
of cultivation of diatoms. Approximate concentration of SiO2 in the inclusions is
1-4%. It is assumed that silica in the inclusions is present as gelatinized
silica-gel. These results explain the possible mechanism of transport of silicic
acid into the cell against the concentration gradient.
PMID- 28421443
TI - Genomic mapping of chromatin proteins by using Daminv modification of an FLP
dependent DamID approach.
AB - To identify interactions of chromatin proteins with the genome of the cell type
of interest that is a part of heterologous tissues and organs of Drosophila, an
FLP-dependent DamID approach was recently developed [4], which does not require
sorting of cells or nuclei. Here, a modification of this approach, Daminv, is
described. The modified approach was validated by generating the binding pattern
of the LAM protein, a component of the inner membrane of the nuclear envelope,
with the genome of glial cells of the Drosophila larval central brains.
PMID- 28421444
TI - Long-term hyperthermia impairs activity of both photosystems.
AB - This is the first study to perform a simultaneous analysis of the activity of
photosystem 1 and photosystem 2 after long-term exposure to elevated temperature.
It was found that the quantum yield of photochemical reactions decreases in both
photosystems. It is shown that, in photosystem 2, the regulated nonphotochemical
quenching decreases whereas the unregulated non-photochemical quenching
increases. In photosystem 1, limitation on both acceptor and donor sides
increases.
PMID- 28421445
TI - Characterization of new modular nanotransporters with albumin-binding domain.
AB - The albumin-binding domain (ABD) with a site for its cleavage by tumor proteases
was inserted in the structure of modular nanotransporters (MNTs), chimeric
proteins for the delivery of anticancer drugs into the nuclei of cancer cells.
The effectiveness of this cleavage was tested in both variants of created
construct: "pure" ABD-MNT and the complex with albumin. The introduction of the
ABD module into MNTs had no effect on the binding of MNT with receptors on the
surface of the target cancer cells and on the preferential accumulation of MNTs
in the nuclei of these cells. The use of thermophoresis allowed us to determine
the equilibrium dissociation constants of the ABD-MNT complex with bovine and
human serum albumins.
PMID- 28421446
TI - PRE/TRE elements act as transcription activators in Drosophila S2 Cells.
AB - The Drosophila PRE/TRE elements are DNA targets for Polycomb and Trithorax group
proteins, which control repression and activation of gene transcription,
respectively. In this study, we show that, in transiently transfected Drosophila
S2 cells, bxdPRE activates transcription driven from different promoters. Using
CG32795 gene promoter, we demonstrate that other PRE/TRE elements-Fab7, en, eve,
and CycB-also act as transcription activators in this model system.
PMID- 28421447
TI - Inhibition of P-glycoprotein stimulates cell death under Hypoxia-mimicking
conditions.
AB - The most common drug resistance mechanism in tumor cells is expression on their
surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels
chemotherapeutic agents from the interior. An imitation of the hypoxic condition
by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF
1alpha) stabilization and inhibition of doxorubicin-induced apoptosis in colon
cancer NST116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation
leading to cell death induction. Considering these results, P-gp may be used as a
potential target to stimulate chemotherapeutic drugs activity that will
contribute to more efficient tumor cells elimination.
PMID- 28421448
TI - The bxdPRE/TRE element terminates passing through transcription.
AB - The regulation of PRE/TRE activity is required for appropriate tissue and stage
specific gene expression. However, the molecular principles of PRE/TRE activity
control remain unknown. Here we show that PRE/TRE element from Ubx regulatory
region efficiently terminates passing through transcription.
PMID- 28421449
TI - Flow cytometric analysis of the ERCC1, marker of DNA damage repair, in the tumor
specimens embedded into paraffin blocks.
AB - The differences in expression of ERCC1 were estimated between tumor specimens
embedded into paraffin blocks and surgical biopsy specimens of non-small cell
lung cancer as well as breast and ovarian cancers. Concordance or differences not
higher than 20% were observed in 73% of the cases. The number of the cases with
more significant differences in ERCC1 expression was less than 17%. The results
show that ERCC1 detection in surgical biopsy specimens by flow cytometry is the
more preferable method due to reduced preanalytical phase of the analysis.
PMID- 28421450
TI - The level of proapoptotic gene transcripts in wheat leaves under high temperature
stress.
AB - Under exposure of wheat plants to high temperatures (33, 37, and 43 degrees C),
the level of transcripts of the genes encoding proapoptotic proteins-TaMCAII
(encodes type II metacaspase) and TaBAX (functional homologue of the CDF1 gene of
Arabidopsis thaliana)-in leaf cells increased. This process at temperatures of 37
and 43 degrees C passed ahead of (in the case of TaBAX mRNA) or was accompanied
by (in the case of TaMCAII mRNA) the emergence of signs of nucleosomal DNA
degradation in leaves. The accumulation of malondialdehyde in the leaves of
seedlings exposed to temperatures of 37 and 43 degrees C coincided in time with a
change in the TaMCAII gene expression and the emergence of signs of programmed
cell death.
PMID- 28421451
TI - Mathematical model of polymerase chain reaction with temperature-dependent
parameters.
AB - The course of the real-time polymerase chain reaction (PCR) is determined by the
temperature dependence of the kinetics of the component reactions, particularly
the DNA strand hybridization. To investigate the effect of thermal processes on
the reaction behavior, a mathematical model in which the variable rate constant
of dissociation of "primer-single strand" complexes depends on temperature was
proposed. The reaction medium temperature, which depends on time, was also
introduced into the model. The proposed model of real-time PCR makes it possible
to analyze different aspects of the reaction, which are important for the
development of instruments and reagents for PCR.
PMID- 28421452
TI - Susceptibility of Candida albicans from Cystic Fibrosis Patients.
AB - Candida albicans is a common microbe, colonizer and potential pathogen found in
respiratory cultures of cystic fibrosis (CF) patients. Because of possible
development of resistance in patient isolates resulting from residence in the
abnormal milieu of CF patient airways, or from exposure to antifungals, and
considering the possibility of patient-to-patient spread of microbes and reports
of elevated resistance to other fungal pathogens, it was important to assay the
susceptibility of isolates of Candida and compare that profile to isolates from
the community. In our center, and unlike another fungal pathogen, no increase in
resistance of Candida isolates of the CF cohort was found.
PMID- 28421453
TI - Psychological Determinants of Medication Adherence in Stroke Survivors: a
Systematic Review of Observational Studies.
AB - BACKGROUND: Medications targeting stroke risk factors have shown good efficacy,
yet adherence is suboptimal. To improve adherence, its determinants must be
understood. To date, no systematic review has mapped identified determinants into
the Theoretical Domains Framework (TDF) in order to establish a more complete
understanding of medication adherence. PURPOSE: The aim of this study was to
identify psychological determinants that most influence stroke survivors'
medication adherence. METHODS: In line with the prospectively registered protocol
(PROSPERO CRD42015016222), five electronic databases were searched (1953-2015).
Hand searches of included full text references were undertaken. Two reviewers
conducted screening, data extraction and quality assessment. Determinants were
mapped into the TDF. RESULTS: Of 32,825 articles, 12 fulfilled selection criteria
(N = 43,984 stroke survivors). Tested determinants mapped into 8/14 TDF domains.
Studies were too heterogeneous for meta-analysis. Three TDF domains appeared most
influential. Negative emotions ('Emotions' domain) such as anxiety and concerns
about medications ('Beliefs about Consequences' domain) were associated with
reduced adherence. Increased adherence was associated with better knowledge of
medications ('Knowledge' domain) and stronger beliefs about medication necessity
('Beliefs about Consequences' domain). Study quality varied, often lacking
information on sample size calculations. CONCLUSIONS: This review provides
foundations for evidence-based intervention design by establishing psychological
determinants most influential in stroke survivors' medication adherence. Six TDF
domains do not appear to have been tested, possibly representing gaps in research
design. Future research should standardise and clearly report determinant and
medication adherence measurement to facilitate meta-analysis. The range of
determinants explored should be broadened to enable more complete understanding
of stroke survivors' medication adherence.
PMID- 28421454
TI - Quality Indicators in Endoscopic Ablation for Barrett's Esophagus.
AB - OPINION STATEMENT: Barrett's esophagus (BE) is a well-established premalignant
condition for esophageal adenocarcinoma (EAC); a cancer that is associated with a
poor 5-year survival rate. Several strategies have been explored in the context
of reducing the burden of EAC. Endoscopic eradication therapy (EET) is considered
the standard of care for the management of patients with BE with dysplasia and
early neoplasia; a practice that has been endorsed by all gastroenterology
societal guidelines. The effectiveness of EET has been demonstrated in multiple
studies and contemporary management includes a combination of endoscopic mucosal
resection (EMR) of all visible lesions followed by eradication of the remaining
BE using ablative techniques of which radiofrequency ablation (RFA) has the best
evidence supporting effectiveness and safety. These techniques are being used
increasingly at academic tertiary care centers and community practices. In this
era of value-based health care, there is increased focus on the establishment,
documentation, and reporting of quality indicators; indicators that are important
to physicians, patients, and payers. The purpose of this review is to highlight
the current status of quality indicators in EET for the management of patients
with BE-related neoplasia and discuss the future steps required to ensure that
these quality indicators are uniformly incorporated into practice.
PMID- 28421455
TI - Erratum to: Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the
Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double
Blind, Vehicle-Controlled Trial.
PMID- 28421456
TI - Filling the Void: A Review of Intragastric Balloons for Obesity.
AB - Endoscopic bariatric therapies are predicted to become much more widely used in
North America for obese patients who are not candidates for bariatric surgery. Of
all the endoscopic bariatric therapies, intragastric balloons (IGBs) have the
greatest amount of clinical experience and published data supporting their use.
Three IGBs are FDA approved and are now commercially available in the USA
(Orbera, ReShape Duo, and Obalon) with others likely soon to follow. They are
generally indicated for patients whose BMI ranges from 30 to 40 mg/kg2 and who
have failed to lose weight with diet and exercise. IGBs have been shown to be
safe, effective, and relatively straightforward to place and remove.
Accommodative symptoms commonly occur within the initial weeks post-placement;
however, major complications are rare. Gastric ulceration can occur in up to 10%
of patients, while balloon deflation with migration and bowel obstruction occurs
in <1% of patients. The effectiveness of the Orbera and ReShape Duo IGBs ranges
from 25 to 50% EWL (excess weight loss) after 6 months of therapy. The use of
IGBs is likely to grow dramatically in the USA, and gastroenterologists and
endoscopists should be familiar with their indications/contraindications,
efficacy, placement/removal, and complications.
PMID- 28421457
TI - KLF15 Inhibits Cell Proliferation in Gastric Cancer Cells via Up-Regulating
CDKN1A/p21 and CDKN1C/p57 Expression.
AB - BACKGROUND: Kruppel-like factors (KLFs) have been identified in multi-cancers and
act as oncogenes or tumor suppressors. The function of KLF15, one member of KLFs,
has not been well elucidated, especially in gastric cancer (GC). AIMS: This study
was designed to investigate the prognostic value and biological functions of
KLF15 in GC. METHODS: KLF15 protein expression in GC patients was evaluated by
immunohistochemistry assays in 50 paired GC tissues and adjacent normal tissues,
and correlations between KLF15 expression and clinicopathological characteristics
and prognosis were analyzed. Then, we investigated the over-expression of KLF15
on cell proliferation and its mechanism in GC cells. RESULTS: KLF15 expression
levels were significantly down-regulated in GC tissues compared to adjacent
normal tissues. And KLF15 expression was negatively correlated with clinical
stage, lymphatic metastasis, and distant metastasis. Furthermore, KLF15
expression could predict prognosis in patients with GC. Moreover, over-expression
of KLF15 could inhibit cell proliferation partly via regulating CDKN1A/p21 and
CDKN1C/p57. CONCLUSION: These findings demonstrate that KLF15 plays a significant
role in GC progression and could be a therapeutic target for GC.
PMID- 28421458
TI - Surgical Management of Pancreatic Cysts: A Shifting Paradigm Toward Selective
Resection.
AB - Due to the widespread use of high-quality cross-sectional imaging, pancreatic
cystic neoplasms are being diagnosed with increasing frequency. Clinicians are
therefore asked to counsel a growing number of patients with pancreatic cysts
diagnosed incidentally at an early, asymptomatic stage. Over the last two
decades, accumulating knowledge on the biologic behavior of these neoplasms along
with improved diagnostics through imaging and endoscopic cyst fluid analysis have
allowed for a selective therapeutic approach toward these neoplasms. On one end
of the management spectrum, observation is recommended for typically benign
lesions (serous cystadenoma), and on the other end, upfront resection is
recommended for likely malignant lesions (main duct IPMN, mucinous cystadenoma,
solid pseudopapillary tumor, and cystic pancreatic neuroendocrine tumors). In
between, management of premalignant lesions (branch duct IPMN) is dictated by the
presence of high-risk features. In general, resection should be considered
whenever the risk of malignancy is higher than the risk of the operation. This
review aims to describe the evolution and current status of evidence guiding the
selection of patients with pancreatic cystic neoplasms for surgical resection,
along with a specific discussion on the type of resection required and expected
outcomes.
PMID- 28421459
TI - Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a
genome-wide analysis.
AB - According to the recently updated World Health Organization (WHO) classification
(2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant
groups, the latter being significantly less aggressive in terms of both
progression-free and total survival. We identified a small cohort of WHO grade II
III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both
immunohistochemistry and molecular sequence analysis, which nonetheless had
unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among
these four cases, the mean time to recurrence as glioblastoma was only 16 months
and the mean total survival among the three patients who have died during the
follow-up was only 31 months. We hypothesized that these tumors had other,
unfavorable genetic or epigenetic alterations that negated the favorable effect
of the IDH mutation. We applied genome-wide profiling with a methylation array
(Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic
alterations in these tumors. As expected, the methylation profiles of all four
tumors were found to match most closely with IDH-mutant astrocytomas. Compared
with a control group of four indolent, age-similar WHO grade II-III astrocytomas,
the tumors showed markedly increased levels of overall copy number changes, but
no consistent specific genetic alterations were seen across all of the tumors.
While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a
subset may rapidly recur and progress to glioblastoma. The precise underlying
cause of the increased aggressiveness in these gliomas remains unknown, although
it may be associated with increased genomic instability.
PMID- 28421460
TI - Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles
to gliomas.
AB - The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide
derived from human immunodeficiency virus-1. It has been used to facilitate
macromolecule delivery to various cell types. This cationic peptide is capable of
crossing the blood-brain barrier and therefore might be useful for enhancing the
delivery of drugs that target brain tumors. Here we test the efficiency with
which relatively small (20 nm) micelles can be delivered by an intra-arterial
route specifically to gliomas. Utilizing the well-established method of flow
arrest intra-arterial injection we compared the degree of brain tumor deposition
of cationic TAT-decorated micelles versus neutral micelles. Our in vivo and post
mortem analyses confirm glioma-specific deposition of both TAT-decorated and
neutral micelles. Increased tumor deposition conferred by the positive charge on
the TAT-decorated micelles was modest. Computational modeling suggested a
decreased relevance of particle charge at the small sizes tested but not for
larger particles. We conclude that continued optimization of micelles may
represent a viable strategy for targeting brain tumors after intra-arterial
injection. Particle size and charge are important to consider during the directed
development of nanoparticles for intra-arterial delivery to brain tumors.
PMID- 28421461
TI - The role of tumor board conferences in neuro-oncology: a nationwide provider
survey.
AB - The tumor board or multidisciplinary cancer meeting (MCM) is the foundation of
high value multidisciplinary oncology care, coordinating teams of specialists.
Little is known on how these meetings are implemented in Neuro-oncology. Benefits
of MCMs include coordination, direction for complicated cases, education, and a
forum for communication, emerging technology, and clinical trials. This study
identifies participation and utilization of neuro-oncology MCMs. A cross
sectional descriptive survey was dispersed through an internet questionnaire. The
Society of Neuro-Oncology and the American Brain Tumor Association provided a
list of dedicated neuro-oncology centers. All National Cancer Institute
designated centers, and participants in the Adult Brain Tumor Consortium or the
Brain Tumor Trials Collaborative were included, identifying 85 centers.
Discussion included primary brain tumors (100%), challenging cases (98%),
recurrent disease (96%), neoplastic spine disease (93%), metastatic brain lesions
(89%), pre-surgical cases (82%), pathology (76%), and paraneoplastic disease
(40%). MCMs were composed of neuro-oncologists, neurosurgeons, and radiation
oncologists (100%), radiologists (98%), pathologists (96%), and clinical trial
participants (64%). Individual preparation ranged from 15 to 300 min. MCMs were
valued for clinical decision making (94%), education (89%), and access to
clinical trials (69%). 13% documented MCMs in the medical record. 38% of centers
used a molecular tumor board; however, many commented with uncertainty as to how
this is defined. Neuro-oncology MCMs at leading U.S. institutions demonstrate
congruity of core disciplines, cases discussed, and perceived value. We
identified variability in preparation time and implementation of MCM
recommendations. There is high uncertainty as to the definition and application
of a molecular tumor board.
PMID- 28421462
TI - Molecular alterations in pediatric gliomatosis cerebri are similar to those in
less invasive forms of pediatric diffuse glioma.
PMID- 28421463
TI - ZEB1 expression in Chinese lower-grade gliomas.
PMID- 28421464
TI - A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive
Adrenocortical Carcinoma.
AB - Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations
mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT)
transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to
poorer outcomes in other malignancies, but their role in ACC is unknown. We
describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at
age 76. After primary tumor resection, mitotane therapy was started as palliation
to low-volume liver metastasis. After a 2-year period of stable disease, the
patient died due to brain metastasis. Somatic gene sequencing revealed a novel
TP53 mutation in DNA extracted from paraffin-embedded tissue, a deletion of 8bp
in exon 8 (c.811_818del8; GAGGTGCG/-) in homo or hemizygosis causing a subsequent
frameshift and premature stop codon at position 302. Immunohistochemistry of P53
and p-Ser-15 P53 showed absent tumoral staining. In addition, immunohistochemical
analysis showed an increased expression of the mesenchymal markers vimentin and
fibronectin. At last, EMT transcription factors TWIST1 and SIP1 were also
overexpressed in tumoral cells. This case report describes an aggressive ACC with
not only a novel somatic mutation, but also a novel International Agency for
Research on Cancer database 8 base-pair deletion in TP53 exon 8. In addition, the
expression of EMT inducers TWIST1 and SIP1 have been reported for the first time
in an ACC case. Further investigation is needed to clarify the biologic
significance of this new TP53 mutation and its role in the EMT process.
PMID- 28421465
TI - The Role of the Molecular Clock in Skeletal Muscle and What It Is Teaching Us
About Muscle-Bone Crosstalk.
AB - PURPOSE OF REVIEW: This review summarizes what has been learned about the
interaction between skeletal muscle and bone from mouse models in which BMAL1, a
core molecular clock protein has been deleted. Additionally, we highlight several
genes which change following loss of BMAL1. The protein products from these genes
are secreted from muscle and have a known effect on bone homeostasis. RECENT
FINDINGS: Circadian rhythms have been implicated in regulating systems
homeostasis through a series of transcriptional-translational feedback loops
termed the molecular clock. Recently, skeletal muscle-specific disruption of the
molecular clock has been shown to disrupt skeletal muscle metabolism.
Additionally, loss of circadian rhythms only in adult muscle has an effect on
other tissue systems including bone. Our finding that the expression of a subset
of skeletal muscle-secreted proteins changes following BMAL1 knockout combined
with the current knowledge of muscle-bone crosstalk suggests that skeletal muscle
circadian rhythms are important for maintenance of musculoskeletal homeostasis.
Future research on this topic may be important for understanding the role of the
skeletal muscle molecular clock in a number of diseases such as sarcopenia and
osteoporosis.
PMID- 28421467
TI - Coronary physiology revisited.
PMID- 28421466
TI - Parathyroid Diseases and T Cells.
AB - PURPOSE OF REVIEW: This review summarizes studies into the permissive role of T
cells in the bone catabolic effects of hyperparathyroidism and parathyroid
hormone (PTH). RECENT FINDINGS: Work in animals combined with recent
translational studies in humans now highlight the potent amplificatory action of
T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a
complex pathway by which PTH exploits natural self-renewal functions of CD4+ T
cells, to drive TNFalpha production that promotes formation of IL-17A secreting
Th17 T cells. TNFalpha and IL-17 further amplify osteoblastic receptor activator
of NF-kappaB ligand (RANKL) production and down-modulate osteoprotegerin (OPG),
establishing conditions propitious for osteoclastic bone resorption. These
findings are consistent with, and add to, the traditional view of PTH-induced
bone loss involving only osteoblast-lineage cells. T cells potently amplify
traditional pathways and provide permissive costimulatory signals to bone marrow
stromal cells, facilitating the development of an increased RANKL/OPG ratio
favourable to bone resorption and bone loss.
PMID- 28421468
TI - Gambling in rhesus macaques (Macaca mulatta): The effect of cues signaling risky
choice outcomes.
AB - Preference for a larger-variable "risky" option over a smaller-reliable "safe"
option often depends upon the likelihood that the risky option will deliver a
sufficiently sized reward to have an equivalent or superior expected value.
However, preference for the risky option has been shown to increase under
conditions where informative stimuli signaling the outcome of a risky choice is
included between the choice and the outcome and this risk-prone preference
persists even when the risky option has a lower expected value than the
alternative safe option. In the present study, rhesus macaques chose between a
risky option and a safe option across two experimental phases to determine
whether the outcome signal affected the degree of preference for the risky
option. Overall, six out of seven macaques showed a greater preference for the
risky option in the signaled condition than in the unsignaled condition. The
macaques' risky choices were sensitive to the expected value of the risky option
and the signaled condition produced a general increase in risky choices
independently of the expected value of the risky outcome. Overall, these results
are consistent with those obtained with other animals, and this may relate to a
process where animals show a biased preference for "good news." This process may
model some of the relevant factors that explain the psychology of gambling in
humans.
PMID- 28421469
TI - Effectiveness and Safety of Different Once-Daily Doses of Adrenocorticotropic
Hormone for Infantile Spasms.
AB - INTRODUCTION: Adrenocorticotropic hormone (ACTH) has been commonly used as a
first-line treatment for infantile spasms (IS), but its optimal dose and duration
are still unclear. This study is the largest retrospective cohort to document the
therapeutic efficacy and tolerability for three gradient doses of ACTH in
IU/kg/day units in Chinese patients. OBJECTIVE: The aim of our study was to
elucidate the effectiveness and safety of three different low doses and duration
of ACTH treatment for IS in China. METHODS: We conducted a retrospective, chart
review of IS cases that were treated with biologic short-acting ACTH and followed
up for at least 6 months at a single center in China between June 2010 and June
2016. In total, 200 children met the inclusion criteria. Cases were divided into
three groups according to dosage (1, 1.1-1.9, and 2-4 IU/kg/day). Furthermore, we
divided the 2-4 IU/kg/day group into 2-3 and 3.1-4 IU/kg/day subgroups. All
groups were evaluated for response rates, relapse rates, and adverse effects.
RESULTS: Electroclinical remission by day 14 occurred in 41.4% of infants given 2
4 IU/kg/day and 36.4% of infants given 1.1-1.9 IU/kg/day, compared with only
14.7% of patients given 1 IU/kg/day (p = 0.004 and 0.03, respectively).
Prolonging ACTH treatment for up to 28 days improved response by 24% in all 200
infants. Overall, 73.9% of infants receiving 2-4 IU/kg/day responded,
significantly higher than the 52.7% responding to 1.1-1.9 IU/kg/day and the 23.5%
responding to 1 IU/kg/day (p < 0.01). There was no significant difference in the
number of relapses or adverse effects in the three groups. Moreover, in the 2-4
IU/kg/day group, 74.7% of children receiving 2-3 IU/kg/day of ACTH responded,
compared with 70% who responded to 3.1-4 IU/kg/day (p = 0.78). CONCLUSIONS: ACTH
at a dosage of 2-3 IU/kg/day is superior to 1.1-1.9 and 1 IU/kg/day dosages, is
as good as a 3.1-4 IU/kg/day dosage in terms of response rate, and causes no more
adverse effects or relapses than other dosages. In addition, prolonging the
duration of ACTH treatment can improve response.
PMID- 28421470
TI - Adrenalectomy: indications and options for treatment.
AB - The history of adrenal surgery is longstanding. Firstly described in 1889 by
Thornton, the open adrenalectomy has been for decades the only surgical approach
to adrenal diseases. Nowadays, instead, several approaches to adrenal glands have
been described in the literature, such as laparoscopic adrenalectomy, robotic
assisted procedure and single-incision technique. Actually, laparoscopic
adrenalectomy is considered as the gold standard treatment for adrenal lesions.
In fact, all functional tumors, including pheochromocytoma, are candidates for a
laparoscopic approach in the absence of other contraindications. In the adrenal
gland surgery, it is important to consider that a multidisciplinary approach
which comprises surgeons, anesthesiologists, endocrinologists, and oncologists
plays an important role in the management of patients and that the success of the
procedure is related also to surgeon experience and hospital volume. This review
aims to discuss the indications for adrenalectomy and to describe the different
techniques options for the adrenal gland surgery.
PMID- 28421471
TI - Social Marketing as a Framework for Youth Physical Activity Initiatives: a 10
Year Retrospective on the Legacy of CDC's VERB Campaign.
AB - PURPOSE OF REVIEW: In 2002, the U.S. Centers for Disease Control and Prevention
(CDC) launched the VERB. It's what you do! campaign to increase physical activity
among tweens and concomitantly respond to the rise in childhood obesity. This
retrospective study summarizes the history of the VERB campaign's social
marketing approach and its effectiveness in promoting behavior change in the
targeted population. RECENT FINDINGS: The legacy of VERB, which ended in 2006, is
discussed, with an emphasis on examining initiatives over the last decade and the
degree to which they followed (or did not follow) the structural and thematic
lead of the campaign. The article ends with suggestions for how VERB still has
the potential to inform other social marketing campaigns going forward.
PMID- 28421473
TI - Personality, emotion-related variables, and media pressure predict eating
disorders via disordered eating in Lebanese university students.
AB - PURPOSE: Disordered eating behaviors are on the rise among youth. The present
study investigates psychosocial and weight-related variables as predictors of
eating disorders (ED) through disordered eating (DE) dimensions (namely
restrained, external, and emotional eating) in Lebanese university students.
METHODS: The sample consisted of 244 undergraduates (143 female) aged from 18 to
31 years (M = 20.06; SD = 1.67). Using path analysis, two statistical models were
built separately with restrained and emotional eating as dependent variables, and
all possible direct and indirect pathways were tested for mediating effects. The
variables tested for were media influence, perfectionism, trait emotional
intelligence, and the Big Five dimensions. RESULTS: In the first model, media
pressure, self-control, and extraversion predicted eating disorders via emotional
eating. In the second model, media pressure and perfectionism predicted eating
disorders via restrained eating. DISCUSSION: Findings from this study provide an
understanding of the dynamics between DE, ED, and key personality, emotion
related, and social factors in youth. Lastly, implications and recommendations
for future studies are advanced.
PMID- 28421472
TI - Screen Time, Other Sedentary Behaviours, and Obesity Risk in Adults: A Review of
Reviews.
AB - PURPOSE OF REVIEW: The aim of this paper is to assess the association between
sedentary behaviours, including screen time, and risk of obesity in adults. A
review of 10 systematic reviews was undertaken. RECENT FINDINGS: Available
evidence is generally not supportive of associations between sedentary behaviour
and obesity in adults. Most studies that found significant associations indicated
mostly small effect sizes. Somewhat more consistent associations were shown for
screen time (mainly TV viewing), among older adults, and for pre-adult sedentary
behaviour to increase the risk of obesity in adulthood. Some evidence also exists
for breaks in sedentary time to be associated with a more favourable BMI, and for
use of a car to be associated with greater risk of obesity. There is limited
evidence for an association between sedentary behaviour in adulthood and obesity
and any association that exists does not seem to be causal. Future research is
required investigating potentially positive effects for frequent breaks from
sitting, less car use, and an uncoupling of TV viewing and dietary intake.
PMID- 28421474
TI - Social safeness and disordered eating: Exploring underlying mechanisms of body
appreciation and inflexible eating.
AB - Feelings of social safeness and connectedness have been associated with adaptive
emotion regulation processes and well-being indicators. Further, literature has
demonstrated that interpersonal experiences play an important role in the
etiology and maintenance of body and eating psychopathology. However, the study
of the role of social variables and emotion regulation processes in the
engagement in inflexible eating rules and eating psychopathology is still in its
early stages. The current study aims to fill some gaps within the literature and
explore the mediator role of body appreciation and inflexible eating rules in the
link between social safeness and disordered eating. Participants were 253 women,
aged between 18 and 50 years old, who completed a series of online self-report
measures. Results from the tested path analysis model showed that social safeness
holds a significant effect on eating psychopathology, through the mechanisms of
body appreciation and inflexible eating rules. Also, results suggested that women
who present higher levels of social safeness tend to present a more positive and
respectful attitude towards their body and decreased adoption of inflexible
eating rules, which seem to explain lower levels of disordered eating behaviours.
These findings seem to present empirical support for the development of
intervention programs that promote a positive, affectionate and healthy
relationship with one's body image, in order to prevent the inflexible adherence
to eating rules and disordered eating behaviours.
PMID- 28421476
TI - Academic Productivity in Psychiatry: Benchmarks for the H-Index.
AB - OBJECTIVE: Bibliometrics play an increasingly critical role in the assessment of
faculty for promotion and merit increases. Bibliometrics is the statistical
analysis of publications, aimed at evaluating their impact. The objective of this
study is to describe h-index and citation benchmarks in academic psychiatry.
METHODS: Faculty lists were acquired from online resources for all academic
departments of psychiatry listed as having residency training programs in Canada
(as of June 2016). Potential authors were then searched on Web of Science
(Thomson Reuters) for their corresponding h-index and total number of citations.
RESULTS: The sample included 1683 faculty members in academic psychiatry
departments. Restricted to those with a rank of assistant, associate, or full
professor resulted in 1601 faculty members (assistant = 911, associate = 387,
full = 303). h-index and total citations differed significantly by academic rank.
Both were highest in the full professor rank, followed by associate, then
assistant. The range in each, however, was large. CONCLUSIONS: This study
provides the initial benchmarks for the h-index and total citations in academic
psychiatry. Regardless of any controversies or criticisms of bibliometrics, they
are increasingly influencing promotion, merit increases, and grant support. As
such, benchmarking by specialties is needed in order to provide needed context.
PMID- 28421475
TI - Association of white and red meat consumption with general and abdominal obesity:
a cross-sectional study among a population of Iranian military families in 2016.
AB - PURPOSE: To assess the association of red and white meat consumption with general
and abdominal obesity among Iranian military families. METHODS: In this cross
sectional study, 525 subjects with age range of 19-55 years belong to military
families of Army of Islamic Republic of Iran were recruited during 2016. Dietary
data were collected using semi-quantitative food-frequency questionnaire. A self
reported questionnaire was used to collect data on demographic characteristics
and anthropometric measurements. General obesity was defined as body mass index
>=25 kg/m2 and abdominal obesity as waist circumference >=80 cm for women and >=
94 cm for men. Finally, we had complete data on 170 subjects for analysis.
RESULTS: Mean age of subjects was 33.78 +/- 6.48. We found a significant positive
association between red meat consumption and abdominal obesity in fully adjusted
model, so that subjects in the fourth quartile had 4.51 more odds to be
abdominally obese compared with those in the first quartile of red meat
consumption (OR 4.51, 95% CI 1.32-15.40). Such relationship was not seen for
general obesity. In addition, white meat consumption was not associated with
general and abdominal obesity either before or after adjustment for covariates.
CONCLUSIONS: Red meat consumption was positively associated with abdominal
obesity. No significant relationship was found between white meat consumption,
and general and abdominal obesity. Therefore, further studies are needed to shed
light our findings.
PMID- 28421477
TI - Collaborative Training Efforts with Pediatric Providers in Addressing Mental
Health Problems in Primary Care.
PMID- 28421478
TI - Facilitating the Feedback Process on a Clinical Clerkship Using a Smartphone
Application.
AB - OBJECTIVES: This pilot study evaluated the effects of a smartphone-triggered
method of feedback delivery on students' perceptions of the feedback process.
METHODS: An interactive electronic feedback form was made available to students
through a smartphone app. Students were asked to evaluate various aspects of the
feedback process. Responses from a previous year served as control. RESULTS: In
the first three quarters of academic year 2014-2015 (pre-implementation), only
65% of responders reported receiving oral feedback and 40% reported receiving
written feedback. During the pilot phase (transition), these increased to 80% for
both forms. Following full implementation in academic year 2015-2016 (post
implementation), 97% reported receiving oral feedback, and 92% reported receiving
written feedback. A statistically significant difference was noted pre- to post
implementation for both oral and written feedback (p < 0.01). A significant
increase from pre-implementation to transition was noted for written feedback (p
< 0.01) and from transition to post-implementation for oral feedback (p < 0.01).
Ninety-one and 94% of responders reported ease of access and timeliness of the
feedback, 75% perceived the quality of the feedback to be good to excellent; 64%
felt receiving feedback via the app improved their performance; 69% indicated the
feedback method as better compared to other methods. Students acknowledged the
facilitation of conversation with supervisors and the convenience of receiving
feedback, as well as the promptness with which feedback was provided. The use of
a drop-down menu was thought to limit the scope of conversation. CONCLUSION:
These data point to the effectiveness of this method to cue supervisors to
provide feedback to students.
PMID- 28421479
TI - Understanding Medical Students' Experience with Stress and Its Related
Constructs: A Focus Group Study from Singapore.
AB - OBJECTIVE: In order to protect medical students from burnout and its untoward
psychiatric effects, it is imperative to understand their stress, burnout,
coping, and resilience experiences. This study aimed to derive collective
definitions from the medical student perspective, to identify common themes of
students' experiences, and to distinguish pre-clinical and clinical year
students' experiences relating to these four constructs. METHODS: The authors
conducted focus groups of medical students in Singapore across 4 years using a
semi-structured question guide. Participants shared their understanding,
experiences, and the relationships between stress, burnout, coping, and
resilience. Coders independently evaluated construct definitions and derived
common themes through an iterative process, and compared transcripts of pre
clinical and clinical year students to determine differences in experience over
time. RESULTS: Nine focus groups (54 students, 28 females, mean age 24.3) were
conducted. Students identified common definitions for each construct. Nine themes
emerged within three domains: (1) relating constructs to personal experience, (2)
interrelating stress, burnout, coping, and resilience, and (3) understanding the
necessity of stress. Compared to clinical students, pre-clinical students
reported theory-based rather than reality-based experiences and exam-induced
stress, defined constructs using present rather than future situations, and
described constructs as independent rather than interrelated. CONCLUSIONS: This
sample of medical students in Singapore shares a common understanding of stress,
burnout, coping, and resilience, but experiences these uniquely. They perceive a
positive role for stress. These findings build upon prior literature, suggesting
an interrelationship between stress and its related constructs and adding the
novel perspective of students from an Asian country.
PMID- 28421480
TI - Amount of Sleep, Daytime Sleepiness, Hazardous Driving, and Quality of Life of
Second Year Medical Students.
AB - OBJECTIVE: The authors describe the sleep habits of second year medical students
and look for associations between reported sleep duration and depression,
burnout, overall quality of life, self-reported academic success, and falling
asleep while driving. METHODS: The authors conducted a cross-sectional
descriptive study of two consecutive cohorts of second year medical students at a
large public university in the USA. Participants completed an anonymous survey
about their sleep habits, daytime sleepiness (Epworth sleepiness scale), burnout
(Maslach burnout inventory), depression (PRIME MD), and perceived stress
(perceived stress scale). Categorical and continuous variables were compared
using chi square tests and t tests, respectively. RESULTS: Sixty-eight percent of
the students responded. Many (34.3%) reported fewer than 7 h of sleep on typical
weeknights, including 6.5% who typically sleep less than 6 h. Twenty-five
students (8.4%) reported nodding off while driving during the current academic
year. Low typical weeknight sleep (fewer than 6 h vs 6-6.9 h vs 7 or more hours)
was associated with (1) higher Epworth sleepiness scale scores, (2) nodding off
while driving, (3) symptoms of burnout or depression, (4) decreased satisfaction
with quality of life, and (5) lower perceived academic success (all p values
<=0.01). Students reporting under 6 h of sleep were four times more likely to nod
off while driving than those reporting 7 h or more. CONCLUSION: Educational,
behavioral, and curricular interventions should be explored to help pre-clinical
medical students obtain at least 7 h of sleep most on weeknights.
PMID- 28421482
TI - Cost-Effectiveness of Stereotactic Radiosurgery and Stereotactic Body Radiation
Therapy: a Critical Review.
AB - PURPOSE OF REVIEW: This review aims to summarize and appraise published cost
effectiveness studies on stereotactic radiosurgery (SRS) and stereotactic body
radiation therapy (SBRT). RECENT FINDINGS: We performed a Medline search of cost
effectiveness studies of SRS, SBRT, and other cancer treatment modalities such as
surgery and systemic therapy from 2006 to 2016. We included studies that used
both modeling and retrospective review techniques. We excluded studies of benign
disease. We defined a strategy whose incremental cost-effectiveness ratio (ICER)
is <=$50,000/quality-adjusted life year (QALY) as "clearly cost-effective," a
strategy whose ICER is <=$100,000/QALY as "probably cost-effective," and a
strategy <=$200,000/QALY as "possibly cost-effective." We appraised modeling
studies by determining whether or not they conform to the International Society
for Pharmacoeconomics and Outcomes Research Good Research Practices (ISPOR) in
modeling task force good research practices in model transparency and validation.
We identified 24 studies that met inclusion criteria. Treatment sites included
brain, bone, liver, lung, pancreas, and prostate. SRS and SBRT were clearly cost
effective strategies in 17 studies, probably cost-effective in 3 studies, and
possibly cost-effective in 2 studies. Of the 16 modeling studies,15 conformed to
transparency best practices; however, only 6 studies performed rigorous
validation as described by the ISPOR guidelines. CONCLUSIONS: SRS and SBRT are
likely to be cost-effective management strategies across a large variety of
treatment sites and techniques. However, rigorous model validation techniques are
lacking in these modeling studies.
PMID- 28421481
TI - Cancer as a Risk Factor for Cardiovascular Disease.
AB - Improvements in early diagnosis and cancer treatments have contributed to high
survival rates for many cancer patients. However, these patients often die of
cardiovascular disease rather than recurrence of their cancer. Heart disease
manifesting after cancer may be due to several mechanisms: shared cardiovascular
risks between cancer and cardiovascular disease, inflammatory states associated
with malignancies, and/or cardiotoxic effects of cancer therapy. Cancer treatment
increases the risk of cardiovascular diseases directly by damaging critical
structures of the heart or indirectly by promoting accelerated atherosclerosis.
Estimating cardiovascular risk by using advanced imaging and monitoring of the
cardiac biomarkers can be used for early detection and treatment of subclinical
cardiac injury. Better knowledge of these early and late cardiac effects in
cancer patients will enable adoption of both primary and secondary prevention
measures of long-term treatment complications in cancer survivors.
PMID- 28421483
TI - Update on Embolization Therapies for Hepatocellular Carcinoma.
AB - PURPOSE OF REVIEW: The purpose of the review is to summarize the latest
applications for embolotherapy in the management of patients with HCC according
to BCLC stage. RECENT FINDINGS: While traditionally reserved for patients with
unresectable HCC and stage B disease, there is an important role for embolization
therapies in earlier stage patients as an adjunct to ablation, bridging, or
downstaging therapy, as a means to improve safety of resection, and potentially
as an arterial ablative option in the case of radioembolization. Newer
applications of radioembolization such as radiation segmentectomy have the
potential to provide cure in localized unifocal disease, and transarterial
chemoembolization-portal vein embolization and radiation lobectomy may provide a
combination of treatment and future liver remnant hypertrophy for planned hepatic
resection. There is also an increasing role for embolization in the treatment of
stage C disease, and recent data suggest it can be used in combination with
sorafenib with the potential for survival benefit over sorafenib alone, even in
the case of portal vein tumor thrombus. Embolization therapies play an
increasingly important role in patients with BCLC stage A-C hepatocellular
carcinoma. While different therapies may be offered on a patient-specific basis,
there are limited prospective RCT data to support superiority of one technique
over another.
PMID- 28421485
TI - Chapter 1 Historical Background on Gamete and Embryo Cryopreservation.
AB - This chapter describes the development of the science of cryopreservation of
gametes and embryos of various species including human. It attempts to record in
brief the main contributions of workers in their attempts to cryopreserve gametes
and embryos. The initial difficulties faced and subsequent developments and
triumphs leading to present-day state of the art are given in a concise manner.
The main players and their contributions are mentioned and the authors' aim is to
do justice to them. This work also attempts to ensure that credit is correctly
attributed for significant advances in gamete and embryo cryopreservation. In
general this chapter has tried to describe the historical development of the
science of cryopreservation of gametes and embryos as accurately as possible
without bias or partiality.
PMID- 28421486
TI - Chapter 2 Utility of Animal Models for Human Ovarian Tissue Cryopreservation.
AB - Success in cryopreservation of ovarian tissue (OT) in animal models has led to
develop efficient cryo-technologies for human ovarian tissue. In this chapter,
cryopreservation protocols developed for animal experiments are described.
PMID- 28421484
TI - The Role of Biomarkers in Detection of Cardio-toxicity.
AB - The goal of this paper is to review the current literature on the role of
biomarkers in the detection and management of patients with cardio-oncologic
disease. The role of biomarker surveillance in patients with known cardiac
disease, as a result of chemotherapy or with the potential to develop cardio
toxicity, will be discussed. In addition, the studies surrounding sub-clinical
cardiac toxicity monitoring during therapy, identification of high-risk patients
prior to therapy, and tailoring oncologic therapies to potential biomarker risk
profiles are reviewed. Based on evidence, to date, troponin and natriuretic
peptides have the greatest potential to detect sub-clinical cardiac dysfunction
and even tailor therapy to prevent progression based on biomarker profiles.
Finally, future directions for potential utilization of novel biomarkers for the
improvement of care of patients in the field of cardio-oncology are discussed.
PMID- 28421487
TI - Chapter 3 Current Challenges in Immature Oocyte Cryopreservation.
AB - Current freezing technology, especially the vitrification method, has markedly
improved oocyte survival rate after warming, and the pregnancy rate is comparable
to that achieved with fresh oocytes. However, most groups report using oocytes
matured in vivo for vitrification. Although immature oocytes can be vitrified
successfully, clinical outcomes do not reach that of vitrification of matured
oocytes. The current literature suggests that oocytes should be vitrified at
mature metaphase II (M-II) stage following IVM rather than at the immature
germinal vesicle (GV) stage, because the potential for oocyte maturation is
reduced when vitrification is performed on immature oocytes at the GV stage.
PMID- 28421488
TI - Chapter 4 Role of Antioxidants and Antifreeze Proteins in
Cryopreservation/Vitrification.
AB - In recent years, supplementation of antioxidants and antifreeze proteins during
cryopreservation/vitrification has significantly improved the survival and
function of oocytes and ovarian tissues (OT) in animal models. In this chapter,
the experimental protocols for the use of antioxidants and antifreeze proteins in
cryopreservation/vitrification are described.
PMID- 28421489
TI - Chapter 5 Slow Freezing of Human Sperm.
AB - Cryopreservation of human spermatozoa is a highly efficient procedure for
managing male fertility, and much of its successful application seems to have a
crucial impact on the reproductive outcome of assisted reproduction technologies.
Here, we present, explain, and describe the slow freezing method for preserving
human spermatozoa, which is currently the most commonly used freezing technique
in most clinical andrology laboratories.
PMID- 28421490
TI - Chapter 6 Technology of Aseptic Cryoprotectant-Free Vitrification of Human ICSI
Spermatozoa.
AB - The aim of this chapter was to describe the standardized aseptic technology of
permeable cryoprotectant-free vitrification of human spermatozoa in capillaries
(for ICSI or IVF in microvolume). Spermatozoa, vitrified by this technology, are
free from seminal plasma owing to swim-up procedure preceding vitrification and
are free from permeable cryoprotectants. They are ready for further use
immediately after warming without any additional treatment.
PMID- 28421491
TI - Chapter 7 Human Epididymal and Testicular Sperm Cryopreservation.
AB - Since the advent of intracytoplasmic sperm injection (ICSI) in the early 1990s,
surgical techniques to recover samples from the epididymis and testis directly
have been used to benefit patients suffering from obstructive and nonobstructive
azoospermia. Various studies have demonstrated comparable fertilization, ongoing
pregnancy, and implantation rates when fresh and frozen-thawed epididymal sperms
were used for ICSI [1]. Injection of fresh and frozen testicular sperms into
mature oocytes resulted in similar fertilization rates in cases of obstructive
azoospermia. However, in cases of nonobstructive azoospermia, the outcome depends
upon the degree of impairment of spermatogenesis, criteria for sperm freezing,
and patient selection [2].
PMID- 28421492
TI - Chapter 8 Human Oocytes Slow-Rate Freezing: Methodology.
AB - Cryopreservation of human oocytes is an important technique for the treatment of
human infertility, as it deals successfully with legal, ethical, and moral issues
related to embryo cryopreservation (Coticchio et al., Human Fertil (Camb) 4:152
157, 2001; Tucker et al., Eur J Obstet Gynecol Reprod Biol 113: 524-527, 2004)
and maintains reproductive potential in women with diseases or conditions that
may compromise reproductive capacity. Here, we describe an oocyte
cryopreservation technique involving slow freezing-rapid thawing with
differential sucrose concentration (0.2 M in the freezing stage-0.3 M in thawing
stage) (Bianchi et al., Reprod Biomed Online. 14:64-71, 2007), describing the
technique in detail, from the preparation of the solutions through to the
performance of the technique and, finally, to a number of helpful hints for
optimum results.
PMID- 28421493
TI - Chapter 9 Slow Freezing and Thawing of Human Cleavage Stage Embryos.
AB - The ability to store human embryos in a viable state at very low temperatures has
been critical to the evolution of responsible practice in clinical Assisted
Reproductive Technology (ART). It has encouraged a reduction in the frequency of
simultaneous multiple embryo transfer and thereby reduced the risks associated
with multiple pregnancy while maintaining high cumulative pregnancy rates from
single oocyte collection cycles. In this chapter, we describe a simple slow
freezing procedure for human early cleavage stage embryos that results in a high
proportion of post-thaw embryos surviving and retaining their implantation
potential.
PMID- 28421494
TI - Chapter 10 Human Oocyte Vitrification.
AB - Discovery and widespread application of successful cryopreservation methods for
MII-phase oocytes was one of the greatest successes in human reproduction during
the past decade. Although considerable improvements in traditional slow-rate
freezing were also achieved, the real breakthrough was the result of introduction
of vitrification. Here we describe the method that is most commonly applied for
this purpose, provides consistent survival and in vitro developmental rates,
results in pregnancy and birth rates comparable to those achievable with fresh
oocytes, and does not result in higher incidence of gynecological or postnatal
complications.
PMID- 28421495
TI - Chapter 11 Human Embryo Vitrification.
AB - Cryopreservation is one of the keystones in clinical infertility treatment. In
particular vitrification has become a well-established and widely used routine
procedure that has allowed important expansion of therapeutic strategies when IVF
is used to treat infertility. Vitrification of human blastocysts allows us to
maximize the potential for conception from any single in vitro fertilization
cycle and prevents wastage of embryos. The technology may even be used to
eliminate fresh embryo transfers for reasons of convenience, uterine receptivity,
fertility preservation, preimplantation genetic diagnosis, or emergency
management. In this chapter, the application of vitrification technology for
cryopreserving human blastocysts will be revealed through step-by-step protocols.
The results that are presented using the described protocols underscore the
robustness of the vitrification technology for embryo cryopreservation.
PMID- 28421496
TI - Chapter 12 Human Ovarian Tissue Slow Freezing.
AB - Cryopreservation of human ovarian tissue is now being accepted as a mainstream
ART laboratory procedure. The procedure described has been validated for use at
the histological and functional level, and, recently, unequivocal evidence of
preservation of primordial follicles has been demonstrated following twin births
from cryopreserved ovarian tissue grafted at a heterotopic site.
PMID- 28421497
TI - Chapter 13 Human Ovarian Tissue Vitrification.
AB - Ovarian freezing and transplantation has garnered increasing interest as a
potential way of preserving fertility in cancer patients as well as for women who
just wish to delay childbearing. This chapter spells out our techniques of
ovarian cortex vitrification and results for frozen compared to fresh ovarian
cortex transplantation (in one single series from one center for the sake of
consistency), as well as potentially provides insight into the mechanism behind
ovarian follicle recruitment. This represents an effort to simplify and
popularize an approach that has yielded favorable results (all cases recovered
ovulation and 75% had successful spontaneous pregnancy) in one single,
disciplined study. It should be clear that this is a review for the more general
reader of our original scientific papers published in Reproductive BioMedicine
Online, New England Journal of Medicine, Fertility and Sterility, Human
Reproduction, Molecular Human Reproduction, and Journal of Assisted Reproduction
and Genetics (JARG).
PMID- 28421498
TI - Chapter 14 Establishing an Oocyte Cryobank Network.
AB - Improvements in oocyte cryopreservation has prompted wider acceptance of this
technology leading to its use for several reasons. Notably, in addition to
elective and medically driven reasons for oocyte cryostorage for fertility
preservation, donor oocyte cryobanking is beginning to gain traction, potentially
replacing fresh oocyte donation in assisted reproduction. Donor "egg banking,"
while not totally analogous to donor sperm banking, does provide strong benefits
in terms of scheduling flexibility and improved clinical efficiencies, while
providing a wider immediate inventory choice. The development of a successful
cryobank "network" and subsequent growth into a full-access donor egg bank are
only possible through adoption of a series of key steps involving establishment
of a repeatable vitrification protocol with a strong clinical record,
incorporation of a comprehensive database and quality management system, and
strict control over the logistics of inventory and shipping and receiving, to
establish a flawless chain from donor to recipient. Confidence will grow in this
potentially difficult process over time.
PMID- 28421499
TI - Chapter 15 Development of a Nationwide Network for Ovarian Tissue
Cryopreservation.
AB - Ovarian tissue cryopreservation is gaining much interest since the publication of
the first live birth after retransplantation of frozen-thawed tissue in 2004
(Donnez et al., Lancet 364:1405-1410, 2004). In contrast to cryopreservation of
gametes and embryos, ovarian tissue freezing is a complex requiring a proper
approach in order to make this a viable option for fertility preservation of
cancer patients. Due to the need in terms of laboratory space, equipment,
personnel, and adequate logistics, an ovarian tissue cryobank is most economic if
managed as a centralized service unit that interacts with numerous clinics
covering the surgical part. Transportation of ovarian tissue under appropriate
conditions from the surgical unit to the cryobank for subsequent preparation and
freezing has been shown to have no impact on cryo-survival (Schmidt et al., Hum
Reprod 18:2654-2659, 2003; Isachenko et al., Fertil Steril 91:1556-1559, 2009).
Several children have been born after retransplantation of such tissue that was
derived from the cryobank in Bonn, Germany (Homepage FertiPROTEKT.
http://www.fertiprotekt.de ). This cryobank is one of the largest in the world
with more than 1300 tissue samples that were frozen from 2003 until today. It is
integrated in the network FertiPROTEKT (Homepage FertiPROTEKT.
http://www.fertiprotekt.de ) and is served by 108 surgical centers that are
located all over Germany. The concept of this cryobank is a blueprint for success
and has recently been used for another regionally centralized cryobank in
Beijing, China. In this chapter the most important topics that need to be
considered while creating a centralized cryobank within a national or regional
network are highlighted.
PMID- 28421500
TI - Chapter 16 Directional Freezing of Ovarian Tissue and Freeze-Drying of Stem Cells
for Fertility Preservation.
AB - Fertility preservation is practiced today for women in their fertile years who
wish or need to postpone or prolong their reproductive era. Currently women have
two main options to preserve their fertility either by oocyte vitrification or by
freezing of ovarian cortical slices. In this chapter we will describe the use of
directional freezing for cortical slices and freeze-drying of stem cells. These
procedures open the way for the preservation of reproductive cells and tissue for
future use in fertility preservation treatments.
PMID- 28421501
TI - Chapter 17 Sterile Plate-Based Vitrification of Adherent Human Pluripotent Stem
Cells and Their Derivatives Using the TWIST Method.
AB - Due to their high biological complexity, e.g., their close cell-to-cell contacts,
cryopreservation of human pluripotent stem cells with standard slow-rate
protocols often is inefficient and can hardly be standardized. Vitrification that
means ultrafast freezing already showed very good viability and recovery rates
for this sensitive cell system, but is only applicable for low cell numbers,
bears a high risk of contamination, and can hardly be implemented under GxP
regulations. In this chapter, a sterile plate-based vitrification method for
adherent pluripotent stem cells and their derivatives is presented based on a
procedure and device for human embryonic stem cells developed by Beier et al.
(Cryobiology 66:8-16, 2013). This protocol overcomes the limitations of
conventional vitrification procedures resulting in the highly efficient
preservation of ready-to-use adherent pluripotent stem cells with the possibility
of vitrifying cells in multi-well formats for direct application in high
throughput screenings.
PMID- 28421502
TI - Chapter 18 Vitrification: A Reliable Method for Cryopreservation of Animal
Embryos.
AB - The impact of cryopreservation in assisted reproduction is increasingly
appreciated. Cells, oocytes, and embryos preserved under ultralow temperature can
endure storage for indefinite time with almost no alteration in their metabolic
and genetic components. Advances in cryopreservation and its applications to
preserve cells, gametes, and embryos offer opportunities in conservation of
biodiversity and dissemination of elite livestock germplasm. This chapter
describes the vitrification for cryopreservation of livestock embryos.
PMID- 28421503
TI - Chapter 19 Cryopreservation Effect on Genetic Function: Neonatal Outcomes.
AB - Cryopreservation is a well-established technique commonly used in clinical
practice. It is used widely for the conservation of gametes and embryos that will
be used later for insemination or in vitro fertilization. However, several
studies have shown that this technique can produce changes in messenger RNA
levels, in the epigenome and induce DNA damage. Although the embryo has potent
mechanisms for DNA repair, and molecular changes in spermatozoa are not
necessarily reflected in the embryo, it is important to explore new molecular
tests and diagnostic tools to design optimal cryopreservation protocols and avoid
undesirable molecular alterations. This chapter describes a protocol to quantify
the lesions produced by cryopreservation using a protocol previously published by
Rothfuss.
PMID- 28421504
TI - Chapter 20 Gavi-Automated Vitrification Instrument.
AB - Gavi is intended for use in a laboratory or clinic environment for the
preparation and vitrification of oocytes, cleavage stage embryos and blastocysts.
Gavi is designed to automate the equilibration steps in the vitrification process
to minimize the variability that occurs during cryopreservation. This automated
process reduces the potential for errors and ensures a standardized, repeatable
procedure for vitrification in a controlled, closed-system environment.
PMID- 28421505
TI - Appendix A: Cryotech(r) Vitrification Thawing.
AB - In the last 15-20 years, many centers are using vitrification as a method of
choice for cryopreservation of human oocytes and embryos. As vitrification
technologies have improved their success profiles, new applications seem to have
emerged, making IVF treatments more successful and more flexible.This appendix
describes the Cryotech(r) method, which is the latest "minimal volume approach"
method, suitable for cryopreservation of oocytes and embryos of any developmental
stage, including blastocysts. Dr. Masashige Kuwayama, who has introduced major
advances in oocyte and embryo cryopreservation, has developed this method. A
detailed protocol has been described with finer tips for the accurate use of the
method for perfect survival and safety.
PMID- 28421506
TI - Appendix B: Solid Surface Vitrification.
AB - Solid surface vitrification method involves direct contact of carrier loaded with
droplet containing gametes or embryos with precooled metal surface. Over the
years, following certain modifications, solid surface vitrification has emerged
as an efficient method for vitrifying human gametes and embryos. Here, we
describe the principle and methodology of solid surface vitrification.
PMID- 28421507
TI - Appendix C: Automated Vitrification of Mammalian Embryos on a Digital
Microfluidic Device.
AB - This chapter introduces a digital microfluidic device that automates sample
preparation for mammalian embryo vitrification. Individual microdroplets
manipulated on the microfluidic device were used as microvessels to transport a
single mouse embryo through a complete vitrification procedure. Advantages of
this approach, compared to manual operation and channel-based microfluidic
vitrification, include automated operation, cryoprotectant concentration gradient
generation, and feasibility of loading and retrieval of embryos.
PMID- 28421508
TI - Appendix D: Irvine Scientific(r) Vitrification System.
AB - This chapter will describe the use of the Irvine Scientific(r) vitrification and
warming solutions (Vit Kits(r)) along with a detailed protocol for the correct
use of the CryoTip(r) vitrification device for human embryos and oocytes.
Successful pregnancies have been reported after carrying out rapid vitrification
methods of oocytes, cleavage stage embryos, and blastocysts using the CryoTip(r)
(Popwell et al. Fertil Steril, 101:e20, 2014; Kuwayama et al. Reprod Biomed
11:608-614, 2005; Kuwayama et al. Fertil Steril 84:S187, 2005; Kuwayama et al.
Vitrification of human embryos using the CryoTip TM method. Reprod Biomed 11:608
614). Compared to other vitrification carrier devices, the CryoTip(r) is
considered a closed carrier for vitrification, thereby eliminating the
theoretical risk of disease transmission through contaminated liquid nitrogen
during cooling and storage (Bielanski et al. Cryobiology, 40:110-116, 2000). The
CryoTip(r) is cleared by the FDA and has CE mark approval as a closed device to
carry gametes or embryos in a specialized medium during cryopreservation
procedures and subsequent long-term storage in liquid nitrogen. The CryoTip(r)
has been shown to be a safe and reliable vitrification device, and when compared
to other open system vitrification devices, it has provided similar results
(Martino et al. Reprod Biol Endocrinol 11:27, 2013, Valbuena et al. Fertil Steril
97:209-217, 2012; Kuwayama et al. Reprod Biomed 11:608-614, 2005). The CryoTip(r)
has also been shown to be suitable for use as a vitrification device for the
cryopreservation of small volumes of sperm (Tanaka et al. Fertil Steril 90: S292,
2008).
PMID- 28421509
TI - Appendix E: Rapid-iTM: Closed Vitrification Device by Vitrolife.
AB - Cryopreservation of gametes and embryos is a growing technique in numerous
reproductive fields including human-assisted reproduction. With improved
understanding of embryo physiology and optimized culture conditions, there are
now more embryos than ever to vitrify for potential use in subsequent cycles.
Many gametes and embryos have been cryopreserved in open systems, but there are
concerns with regard to contamination from the liquid nitrogen and also cross
contamination between patients' germplasm. The development of the Rapid-iTM, a
closed vitrification device that does not use direct contact with liquid nitrogen
during vitrification or subsequent storage, will be discussed as well as clinical
protocols for human oocytes and embryos.
PMID- 28421510
TI - Appendix F: Quinn's Advantage Embryo Freeze Kit.
AB - Despite a large focus on the use of vitrification to cryopreserve embryos in
recent years, there are still arguments for the use of slow freezing for the
cleavage-stage embryo. Having said this, there are lessons to be learned from the
process of vitrification that could be applied to slow freezing to improve post
thaw survival and ultimately clinical pregnancy rates. Specifically, increasing
the concentration of sucrose in the freezing solution from 0.1 to 0.2 M and
subsequently increasing the sucrose concentrations in thawing solutions could
prove beneficial. The use of vitrification warming solutions in the thawing of
slow-frozen embryos may also be an option that not only improves survival but
also streamlines product purchasing and protocols within the laboratory.
PMID- 28421511
TI - Appendix G: Vitrification of Blastocysts Using VitriBlastTM and ThermoBlastTM:
Nidacon.
AB - This appendix describes the vitrification of blastocysts using VitriBlastTM (VBK)
and ThermoBlastTM (TBK) from Nidacon, Molndal, Sweden. The technique used and the
reason for not including DMSO in the medium at the production stage, but
including it separately in the kit, and the importance of collapsing the
blastocyst prior to vitrification will be explained and described.
PMID- 28421512
TI - New Insights into Cockroach Allergens.
AB - PURPOSE OF REVIEW: This review addresses the most recent developments on
cockroach allergen research in relation to allergic diseases, especially asthma.
RECENT FINDINGS: The number of allergens relevant to cockroach allergy has
recently expanded considerably up to 12 groups. New X-ray crystal structures of
allergens from groups 1, 2, and 5 revealed interesting features with implications
for allergen standardization, sensitization, diagnosis, and therapy. Cockroach
allergy is strongly associated with asthma particularly among children and young
adults living in inner-city environments, posing challenges for disease control.
Environmental interventions targeted at reducing cockroach allergen exposure have
provided conflicting results. Immunotherapy may be a way to modify the natural
history of cockroach allergy and decrease symptoms and asthma severity among
sensitized and exposed individuals. The new information on cockroach allergens is
important for the assessment of allergen markers of exposure and disease, and for
the design of immunotherapy trials.
PMID- 28421513
TI - Primary Prevention of Food Allergy.
AB - Food allergy is estimated to affect approximately 8% of children in the USA. This
is a disease without any known treatment or cure and, for some, a disease that
can be quite severe, even life-threatening. While recent advances in potential
treatment have made remarkable strides, with two food-targeted immunotherapy
products now in phase III trials, perhaps the biggest gains in the field have
come in the advent of potential preventative strategies to avoid the development
of food allergy in high-risk individuals. There have been multiple, randomized,
controlled trials (RCTs) performed in the past 5 years that have demonstrated
significant risk reduction from early allergen introduction. These include two
trials for early peanut introduction and five trials for early egg introduction
in the first year of life. The results indicate that primary prevention of food
allergy through early allergen introduction may represent a strategy that could
potentially avert tens of thousands of children from becoming food allergic. In
support of the data for peanut, the National Institute of Allergy and Infectious
Diseases recently sponsored an addendum to the 2010 food allergy guidelines,
specifically recommending peanut be introduced in both high- and standard-risk
infants to reduce the risk of developing peanut allergy. To date, no formal
recommendations have been made for egg, however. This review will focus on the
latest evidence supporting early introduction as a strategy to prevent food
allergy, as well as on practical aspects for its successful implementation.
PMID- 28421514
TI - CORR Insights(r): Vancomycin Prophylaxis for Total Joint Arthroplasty:
Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than
Cefazolin.
PMID- 28421515
TI - CORR Insights(r): Can a Bayesian Belief Network Be Used to Estimate 1-year
Survival in Patients With Bone Sarcomas?
PMID- 28421516
TI - CORR Insights(r): What is the Responsiveness and Respondent Burden of the New
Knee Society Score?
PMID- 28421517
TI - CORR Insights(r): What Is the Timing of General Health Adverse Events That Occur
After Total Joint Arthroplasty?
PMID- 28421518
TI - Empirical research on coordination evaluation and sustainable development
mechanism of regional logistics and new-type urbanization: a panel data analysis
from 2000 to 2015 for Liaoning Province in China.
AB - As the largest developing country in the world, China has witnessed fast-paced
urbanization over the past three decades with rapid economic growth. In fact,
urbanization has been not only shown to promote economic growth and improve the
livelihood of people but also can increase demands of regional logistics.
Therefore, a better understanding of the relationship between urbanization and
regional logistics is important for China's future sustainable development. The
development of urban residential area and heterogeneous, modern society as well
regional logistics are running two abreast. The regional logistics can promote
the development of new-type urbanization jointly by promoting industrial
concentration and logistics demand, enhancing the residents' quality of life and
improving the infrastructure and logistics technology. In this paper, the index
system and evaluation model for evaluating the development of regional logistics
and the new-type urbanization are constructed. Further, the econometric analysis
is utilized such as correlation analysis, co-integration test, and error
correction model to explore relationships of the new-type urbanization
development and regional logistics development in Liaoning Province. The results
showed that there was a long-term stable equilibrium relationship between the new
type urbanization and regional logistics. The findings have important
implications for Chinese policymakers that on the path towards a sustainable
urbanization and regional reverse, this must be taken into consideration. The
paper concludes providing some strategies that might be helpful to the
policymakers in formulating development policies for sustainable urbanization.
PMID- 28421519
TI - Calcite precipitates in Slovenian bottled waters.
AB - Storage of bottled waters in varying ambient conditions affects its
characteristics. Different storage conditions cause changes in the initial
chemical composition of bottled water which lead to the occurrence of
precipitates with various morphologies. In order to assess the relationship
between water composition, storage conditions and precipitate morphology, a study
of four brands of Slovenian bottled water stored in PET bottles was carried out.
Chemical analyses of the main ions and measurements of the physical properties of
water samples were performed before and after storage of water samples at
different ambient conditions. SEM/EDS analysis of precipitates was performed
after elapsed storage time. The results show that the presence of Mg2+, SO42-,
SiO2, Al, Mn and other impurities such as K+, Na+, Ba and Sr in the water
controlled precipitate morphology by inhibiting crystal growth and leading to
elongated rhombohedral calcite crystal forms which exhibit furrowed surfaces and
calcite rosettes. Different storage conditions, however, affected the number of
crystallization nuclei and size of calcite crystals. Hollow calcite spheres
composed of cleavage rhombohedrons formed in the water with variable storage
conditions by a combination of evaporation and precipitation of water droplets
during high temperatures or by the bubble templating method.
PMID- 28421520
TI - Evaluation of passive sampling of gaseous mercury using different sorbing
materials.
AB - Atmospheric mercury monitoring is essential because of its potential human health
and ecological impacts. Current automated monitoring systems include limitations
such as high cost, complicated configuration, and electricity requirements.
Passive samplers require no electric power and are more appropriate for screening
applications and long-term monitoring. Sampling rate is a major factor to
evaluate the performance of a passive sampler. In this study, laboratory
experiments were carried out using an exposure chamber to search for high
efficiency sorbents for gaseous mercury. Four types of sorbents, including sulfur
impregnated carbon (SIC), chlorine-impregnated carbon (CIC), bromine-impregnated
carbon (BIC), and gold-coated sand (GCS) were evaluated under a wide range of
meteorological parameters, including temperature, relative humidity, and wind
speed. The results showed that the four sorbents all have a high sampling rate
above 0.01 m3g-1 day-1, and wind speed has a positive correlation with the
sampling rate. Under different temperature and relative humidity, the sampling
rate of SIC keeps stable. The sampling rate of CIC and BIC shows a negative
correlation with temperature, and GCS is influenced by all the three
meteorological factors. Furthermore, long-term experiments were carried out to
investigate the uptake capacity of GCS and SIC. Uptake curves show that the mass
amount of sorbent in a passive sampler can influence uptake capacity. In the
passive sampler, 0.9 g SIC or 0.9 g GCS can achieve stable uptake efficiency for
at least 110 days with gaseous mercury concentration at or below 2 ng/m3. For
mercury concentration at or below 21 ng/m3, 0.9 g SIC can maintain stable uptake
efficiency for 70 days, and 0.9 g GCS can maintain stability for 45 days.
PMID- 28421521
TI - Selective adsorption of Pb (II) over the zinc-based MOFs in aqueous solution
kinetics, isotherms, and the ion exchange mechanism.
AB - Two series of metal-organic frameworks (MOFs) with similar formula units but
different central metal ions (M) or organic linkers (L), M-BDC (BDC =
terephthalate, M = Zn, Zr, Cr, or Fe), or Zn-L (L = imidazolate-2-methyl, BDC,
BDC-NH2), were prepared and employed as the receptors for adsorption lead ions.
It was found that the Zn-BDC exhibited a much higher adsorption capacity than the
other M-BDC series with various metal ions which have very closely low capacities
at same conditions. Furthermore, the Zn-L (L = imidazolate-2-methyl, BDC, BDC
NH2) still have highly efficient adsorption capacity of lead ions, although the
adsorption capacity varies with different ligand, as well as the adsorption rate
and the equilibrium pH of the solution. This significant high adsorption over Zn
L, different from other M-BDC series with various metal ions (Zr, Cr, or Fe), can
be explained by ion exchange between the central metal ions of Zn-L and lead ion
in solution. Based on the analysis of FT-IR, X-ray diffraction pattern, the
nitrogen adsorption isotherms, the zeta potentials, and the results, a plausible
adsorption mechanism is proposed. When equivalent Zn-L were added to equal volume
of aqueous solution with different concentration of lead ion, the content of zinc
ion in the solution increases with the increase of the initial concentration of
lead ions. The new findings could provide a potential way to fabricate new metal
organic frameworks with high and selective capacities of the heavy metal ions.
PMID- 28421522
TI - Individual and combined inhibition of phenol and thiocyanate on microbial
activity of partial nitritation.
AB - This study evaluated the individual and interactive effect of phenol and
thiocyanate (SCN-) on partial nitritation (PN) activity using batch test and
response surface methodology. The IC50 of phenol and SCN- on PN sludge were 5.6
and 351 mg L-1, respectively. The PN sludge was insensitive to phenol and SCN- at
levels lower than 1.77 and 43.3 mg L-1, respectively. A regression model equation
was developed and validated to predict the relative specific respiration rate
(RSRR) of PN sludge exposed to different phenol and SCN- concentrations. In the
range of independent variables, the most severe inhibition was observed with a
valley value (17%) for RSRR, when the phenol and SCN- concentrations were 4.08
and 198 mg L-1, respectively. An isobole plot was used to judge the combined
toxicity of phenol and SCN-, and the joint inhibitory effect was variable
depending on the composition and concentration of the toxic components.
Furthermore, the toxic compounds showed independent effects, which is the most
common type of combined toxicity.
PMID- 28421523
TI - Response of marine benthic fauna to thin-layer capping with activated carbon in a
large-scale field experiment in the Grenland fjords, Norway.
AB - A field experiment with thin-layer capping was conducted in the Grenland fjords,
Norway, for remediation in situ of mercury and dioxin-contaminated sediments.
Experimental fields at 30 and 95 m depth were capped with (i) powdered activated
carbon (AC) mixed with clay (AC+cla'y), (ii) clay, and (iii) crushed limestone.
Ecological effects on the benthic community and species-feeding guilds were
studied 1 and 14 months after capping, and a total of 158 species were included
in the analyses. The results show that clay and limestone had only minor effects
on the benthic community, while AC+clay caused severe perturbations. AC+clay
reduced the abundance, biomass, and number of species by up to 90% at both 30 and
95 m depth, and few indications of recovery were found during the period of this
investigation. The negative effects of AC+clay were observed on a wide range of
species with different feeding strategies, although the suspension feeding
brittle star Amphiura filiformis was particularly affected. Even though activated
carbon is effective in reducing sediment-to-water fluxes of dioxins and other
organic pollutants, this study shows that capping with powdered AC can lead to
substantial disturbances to the benthic community.
PMID- 28421524
TI - Distance-dependent varieties of microbial community structure and metabolic
functions in the rhizosphere of Sedum alfredii Hance during phytoextraction of a
cadmium-contaminated soil.
AB - The recovery of microbial community and activities is crucial to the remediation
of contaminated soils. Distance-dependent variations of microbial community
composition and metabolic characteristics in the rhizospheric soil of
hyperaccumulator during phytoextraction are poorly understood. A 12-month
phytoextraction experiment with Sedum alfredii in a Cd-contaminated soil was
conducted. A pre-stratified rhizobox was used for separating sub-layer
rhizospheric (0-2, 2-4, 4-6, 6-8, 8-10 mm from the root mat)/bulk soils. Soil
microbial structure and function were analyzed by phospholipid fatty acid (PLFA)
and MicroRespTM methods. The concentrations of total and specified PLFA
biomarkers and the utilization rates for the 14 substrates (organic carbon) in
the 0-2-mm sub-layer rhizospheric soil were significantly increased, as well as
decreased with the increase in the distance from the root mat. Microbial
structure measured by the ratios of different groups of PLFAs such as
fungal/bacterial, monounsaturated/saturated, ratios of Gram-positive to Gram
negative (GP/GN) bacterial, and cyclopropyl/monoenoic precursors and 19:0
cyclo/18:1omega7c were significantly changed in the 0-2-mm soil. The PLFA
contents and substrate utilization rates were negatively correlated with pH and
total, acid-soluble, and reducible fractions of Cd, while positively correlated
with labile carbon. The dynamics of microbial community were likely due to root
exudates and Cd uptake by S. alfredii. This study revealed the stimulations and
gradient changes of rhizosphere microbial community through phytoextraction, as
reduced Cd concentration, pH, and increased labile carbons are due to the
microbial community responses.
PMID- 28421525
TI - The electrochemical selective reduction of NO using CoSe2@CNTs hybrid.
AB - Converting the NO from gaseous pollutant into NH4+ through electrocatalytical
reduction using cost-effective materials holds great promise for pollutant
purifying and resources recycling. In this work, we developed a highly selective
and stable catalyst CoSe2 nanoparticle hybridized with carbon nanotubes
(CoSe2@CNTs). The CoSe2@CNTs hybrid catalysts performed an extraordinary high
selectivity for NH4+ formation in NO electroreduction with minimal N2O production
and H2 evolution. The specific spatial structure of CoSe2 is conductive to the
predominant formation of N-H bond between the N from adsorbed NO and H and
inhibition of N-N formation from adjacent adsorbed NO. It was also the first time
to convert the coordinated NO into NH4+ using non-noble metal catalysis.
Moreover, the original concept of employing CoSe2 as eletrocatalyst for NO
hydrogenation presented in this work can broaden horizons and provide new
dimensions in the design of new highly efficient catalysts for NH4+ synthesis in
aqueous solution.
PMID- 28421526
TI - Impact of the toxicity of Cylindrospermopsis raciborskii (Woloszynska) Seenayya &
Subba Raju on laboratory rats in vivo.
AB - In vivo laboratory studies of toxicity were performed on Wistar rats using a
methanol extract produced by the natural population of Cylindrospermopsis
raciborskii (abundance of 2.13 * 105 trichomes mL-1) collected at Aleksandrovac
Lake (Serbia). HPLC analysis showed that the extract contains 6.65 MUg
cylindrospermopsin (CYN) mg-1. The rats were killed 24 or 72 h after a single
intraperitoneal injection of C. raciborskii extract in concentrations of 1500,
3000, 6000 and 12,000 MUg kg-1 body weight (bw) and an equivalent amount of CYN
as present in the highest dose of the extract (79.80 MUg CYN kg-1 bw). The
genotoxic effect on the livers treated with C. raciborskii was evaluated using
comet assay and potential induction of oxidative stress as the toxicity mechanism
associated with the presence of CYN in extract. The results from the analyses of
DNA damage in the comet tail length, tail moment and percentage of DNA in the
tail in the liver indicated that administration of extract and CYN present
statistically significant difference when compared with the negative control
group. Although an increase in the frequency of selected parameters induced by
the CYN was observed in the liver, this damage was less than the damage resulting
from the administration of the highest dose of extract. The changes in the
biochemical parameters of the hepatic damage showed that the application of
single doses of the extract and CYN did not cause serious liver damage in rats.
The extract and CYN significantly increased oxidative stress in rats' liver after
a single exposure.
PMID- 28421527
TI - Spatio-temporal assessment and trend analysis of surface water salinity in the
coastal region of Bangladesh.
AB - The study was designed to collect water samples over two seasons-wet-monsoon
season (n = 96) (March-April) and dry-monsoon season (n = 44) (September-October)
to understand the seasonal variation in anion and cation hydrochemistry of the
coastal rivers and estuaries contributing in the spatial trend in salinity.
Hydrochemical examination of wet-monsoon season primarily revealed Ca-Mg-HCO3
type (66%) and followed by Na-Cl type (17.70%) water. In the dry-monsoon season,
the scenario reversed with primary water being Na-Cl type (52.27%) followed by Ca
Mg-HCO3 type (31.81%). Analysis of Cl/Br molar ratio vs. Cl (mg/L) depicted
sampling area affected by seawater intrusion (SWI). Spatial analysis by ordinary
kriging method confirmed approximately 77% sample in the dry-monsoon, and 34% of
the wet-monsoon season had shown SWI. The most saline-intruded areas in the wet
monsoon seasons were extreme south-west coastal zone of Bangladesh, lower Meghna
River floodplain and Meghna estuarine floodplain and south-eastern part of
Chittagong coastal plains containing the districts of Chittagong and Cox's Bazar
adjacent to Bay of Bengal. In addition, mid-south zone is also affected slightly
in the dry-monsoon season. From the analyses of data, this study could further
help to comprehend seasonal trends in the hydrochemistry and water quality of the
coastal and estuarine rivers. In addition, it can help policy makers to obligate
some important implications for the future initiatives taken for the management
of land, water, fishery, agriculture and environment of coastal rivers and
estuaries of Bangladesh.
PMID- 28421528
TI - Postnatal LPS Challenge Impacts Escape Learning and Expression of Plasticity
Factors Mmp9 and Timp1 in Rats: Effects of Repeated Training.
AB - Bacterial intoxication associated with inflammatory conditions during development
can impair brain functions, in particular evolutionarily novel forms of memory,
such as explicit learning. Little is known about the dangers of early-life
inflammation on more basic forms of learning, for example, the acquisition of
motor escape abilities, which are generally better preserved under pathological
conditions. To address this limitation in knowledge, an inflammatory response was
elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 MUg/kg) on
postnatal days P15, P18 and P21. The acquisition of escape behaviour was tested
from P77 by active avoidance footshock model and water maze. Open-field behaviour
and blood corticosterone levels were also measured. Rat brain tissue was
collected from pups 2 h post-injection and from adult rats which either underwent
escape training on P77-P81 or remained untrained. mRNA levels of developmental
brain plasticity factors MMP-9 and TIMP-1 were investigated in the medial
prefrontal cortex and ventral/dorsal hippocampus. LPS-challenged rats displayed
moderately deficient escape responses in both memory tests, increased freezing
behaviour and, surprisingly, reduced blood cortisol levels. Mmp9 and Timp1, and
their ratio to one another, were differentially altered in pups versus adult
untrained rats but remained unchanged overall in rats trained in either learning
task. Together, our data indicate that systemic pro-inflammatory response during
early postnatal development has long-lasting effects, including on the
acquisition of motor escape abilities and plasticity factor expression, into
adulthood. Our data suggest that altered stress response could possibly mediate
these deviations and repeated training might generate positive effects on
plasticity under the employed conditions.
PMID- 28421529
TI - Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is
Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia.
AB - Ketamine may prove to be a potential candidate in treating the widespread drug
addiction/substance abuse epidemic among patients with schizophrenia. Clinical
studies have shown ketamine to reduce cocaine and heroin cravings. However, the
use of ketamine remains controversial as it may exacerbate the symptoms of
schizophrenia. Therefore, the aim of this study is to characterize the effects of
ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM)
acetate rat model on operant IV methamphetamine (METH) self-administration. MAM
was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor
activity test and later IV self-administration (IVSA) were then performed in the
male offspring followed by a period of forced abstinence and relapse of METH
taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg)
was administered intraperitoneally 30 min prior to the self-administration
session. As documented previously, the MAM rats showed a lack of habituation in
the locomotor activity test but developed stable maintenance of METH self
administration with no difference in operant behaviour to control animals.
Results show that ketamine treatment significantly reduced the METH intake in the
control animals but not in MAM animals. Ketamine effect on METH self
administration may be explained by increased glutamatergic signalling in the
prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition
of GABA interneurons which was shown to be impaired in the MAM rats. This
mechanism may at least partly explain the clinically proven anti-craving
potential of ketamine and allow development of more specific anti-craving
medications with fewer risks.
PMID- 28421530
TI - Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of
Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.
AB - Occurrence of stroke cases displays a time-of-day variation in human. However,
the mechanism linking circadian rhythm to the internal response mechanisms
against pathophysiological events after ischemic stroke remained largely unknown.
To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R)
injury were investigated in mice in which the ischemic stroke induced at four
different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18).
Besides infarct volume and brain swelling, neuronal survival, apoptosis,
ischemia, and circadian rhythm related proteins were examined using
immunohistochemistry, Western blot, planar surface immune assay, and liquid
chromatography-mass spectrometry tools. Here, we present evidence that midnight
(ZT18; 24:00) I/R injury in mice resulted in significantly improved infarct
volume, brain swelling, neurological deficit score, neuronal survival, and
decreased apoptotic cell death compared with ischemia induced at other time
points, which were associated with increased expressions of circadian proteins
Bmal1, PerI, and Clock proteins and survival kinases AKT and Erk-1/2. Moreover,
ribosomal protein S6, mTOR, and Bad were also significantly increased, while the
levels of PRAS40, negative regulator of AKT and mTOR, and phosphorylated p53 were
decreased at this time point compared to ZT0 (06:00). Furthermore, detailed
proteomic analysis revealed significantly decreased CSKP, HBB-1/2, and HBA
levels, while increased GNAZ, NEGR1, IMPCT, and PDE1B at midnight as compared
with early morning. Our results indicate that nighttime I/R injury results in
less severe neuronal damage, with increased neuronal survival, increased levels
of survival kinases and circadian clock proteins, and also alters the circadian
related proteins.
PMID- 28421531
TI - Retraction Note to "SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and
Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma".
PMID- 28421532
TI - Matrix Metalloproteinase-8 Inhibition Prevents Disruption of Blood-Spinal Cord
Barrier and Attenuates Inflammation in Rat Model of Spinal Cord Injury.
AB - After spinal cord injury (SCI), tight junction (TJ) protein degradation increases
permeability and disrupts the blood-spinal cord barrier (BSCB). The BSCB is
primarily formed of endothelial cell, which forms a specialized tight seal due to
the presence of TJs. BSCB disruption after SCI allows neutrophil infiltration.
Matrix metalloproteinase (MMP)-8 is believed to be mainly expressed by
neutrophils and is quickly released upon neutrophil activation. Here, we
determined whether MMP-8 is involved in the TJ protein degradation in endothelial
cells and also determined its role in the neuroinflammation after SCI. MMP-8
recombinant protein treatment increases the TNF-alpha expression and decreased
the TJ (occludin and zonula occludens-1) protein expression in the endothelial
cells. Likewise, specific MMP-8 inhibitor (MMP-8I) significantly prevented the
TNF-alpha-induced decrease in the expression of TJ protein in endothelial cells.
Furthermore, MMP-8 expression was significantly increased 1 and 3 days after
moderate compression (35 g for 5 min at T10 level) SCI, whereas TJ protein levels
decreased as determined qRT-PCR, western blotting, and immunohistochemistry. MMP
8 was inhibited directly using a MMP-8I (5 mg/kg) and indirectly by reducing
neutrophil infiltration with sivelestat sodium (50 mg/kg) or using the
antioxidant N-acetyl-L-cysteine (100 mg/kg). The MMP-8I significantly decreased
TNF-alpha expression, IL-6, and iNOS expression and increased TJ protein
expression after SCI. In addition, MMP-8I significantly lessens the amount of
Evans blue dye extravasation observed after injury. Thus, our result suggests
that MMP-8 plays an imperative role in inflammation and degradation of TJ
proteins. Increased MMP-8 expression was associated with the early inflammatory
phase of SCI. Inhibiting MMP-8 significantly attenuated SCI-induced inflammation,
BSCB breakdown, and cell injury.
PMID- 28421533
TI - Changes in the Prefrontal Glutamatergic and Parvalbumin Systems of Mice Exposed
to Unpredictable Chronic Stress.
AB - The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known
risk factor of mood disorders including anxiety and depression. Abnormalities in
PFC functioning have been well described in humans displaying stress-induced
depressive symptoms, and hypoactivity of the PFC is now recognized to be a key
feature of the depressed brain. However, little is known about the causes and
mechanisms leading to this altered prefrontal functional activity in the context
of stress-related mood disorders. We previously showed that unpredictable chronic
mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV),
an activity-dependent calcium-binding albumin protein expressed in a specific
subtype of GABAergic neurons, highlighting a potential mechanism through which
chronic stress leads to hypofunction of the PFC. In this study, we aimed to
investigate the mechanisms by which chronic stress alters the prefrontal GABA
system. We hypothesized that chronic stress-induced enhancement of glutamatergic
transmission in the PFC is a crucial contributing factor to changes within the
prefrontal GABAergic and, specifically, PV system. BALB/c male and female mice
were exposed to daily handling (control) or 2 or 4 weeks of UCMS. Female mice
displayed a more severe altered phenotype than males, as shown by increased
anxiety- and depressive-like behaviors and deficits in PFC-dependent cognitive
abilities, particularly after exposure to 2 weeks of UCMS. This behavioral
phenotype was paralleled by a large increase in prefrontal PV messenger RNA
(mRNA) and number of PV-expressing neurons, supporting our previous findings. We
further showed that the expression of pre- and postsynaptic markers of
glutamatergic transmission (VGlut1 presynaptic terminals and pERK1/2,
respectively) onto PV neurons was increased by 2 weeks of UCMS in a sex-specific
manner; this was associated with sex-specific changes in the mRNA expression of
the NR2B subunit of the NMDA receptor. These findings provide evidence of
increased glutamatergic transmission onto prefrontal PV neurons, particularly in
female mice, which could potentially contribute to their increased PV expression
and the extent of their behavioral impairment following UCMS. Finally, our
analysis of activity of subcortical regions sending glutamatergic afferents to
the PFC reveals that glutamatergic neurons from the basolateral amygdala might be
specifically involved in UCMS-induced changes in prefrontal glutamatergic
transmission.
PMID- 28421534
TI - Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C
Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR
T+ Itpr3tf/J Autistic Mouse Model.
AB - Associative studies on a range of neurodevelopmental disorders have identified
relationships between behavioral deficits and immune system function. The BTBR T+
Itpr3tf/J (BTBR) mouse strain displays aberrant characteristics in its social
behavior and immune responses, providing a significant opportunity to examine the
relationship between behavior and the immune system. This study investigated the
influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors
involved in autism in the BTBR mouse model. A2A receptors have previously been
targeted in clinical trials by potential therapeutics with neuroprotective,
immunomodulatory, and analgesic properties. In this study, we examined the
effects of A2A receptor antagonist SCH5826 (SCH) and A2A receptor agonist
CGS21680 (CGS) on C-C and C-X-C chemokine receptors (CCR3, CCR4, CCR5, CCR6,
CCR7, CXCR3, CXCR4, and CXCR5) on splenic CD8+ T cells in the BTBR autistic mouse
model. We also assessed the C-C and C-X-C chemokine receptors mRNA levels in
brain tissue. Our results showed that CCR3+, CCR4+, CCR5+, CCR6+, CCR7+, CXCR3+,
CXCR4+, and CXCR5+ production in splenic CD8+ T cells decreased significantly in
BTBR-CGS-treated mice in comparison with that in BTBR control and BTBR-SCH
treated mice. In addition, RT-PCR analysis revealed decreased gene expression
levels for C-C and C-X-C chemokine receptors in the brain tissue of BTBR-CGS
treated mice, whereas these levels were significantly increased in BTBR control
and BTBR-SCH-treated mice. Our results suggest that treating BTBR mice with CGS
decreases C-C and C-X-C chemokine receptor signaling and might therefore provide
a unique avenue for developing future therapies for autism and neuroimmunological
disorders.
PMID- 28421535
TI - MicroRNA Metabolism and Dysregulation in Amyotrophic Lateral Sclerosis.
AB - MicroRNAs (miRNAs) are a subset of endogenous, small, non-coding RNA molecules
involved in the post-transcriptional regulation of eukaryotic gene expression.
Dysregulation in miRNA-related pathways in the central nervous system (CNS) is
associated with severe neuronal injury and cell death, which can lead to the
development of neurodegenerative disorders, such as amyotrophic lateral sclerosis
(ALS). ALS is a fatal adult onset disease characterized by the selective loss of
upper and lower motor neurons. While the pathogenesis of ALS is still largely
unknown, familial ALS forms linked to TAR DNA-binding protein 43 (TDP-43) and
fused in sarcoma (FUS) gene mutations, as well as sporadic forms, display changes
in several steps of RNA metabolism, including miRNA processing. Here, we review
the current knowledge about miRNA metabolism and biological functions and their
crucial role in ALS pathogenesis with an in-depth analysis on different pathways.
A more precise understanding of miRNA involvement in ALS could be useful not only
to elucidate their role in the disease etiopathogenesis but also to investigate
their potential as disease biomarkers and novel therapeutic targets.
PMID- 28421537
TI - Satb2 Ablation Impairs Hippocampus-Based Long-Term Spatial Memory and Short-Term
Working Memory and Immediate Early Genes (IEGs)-Mediated Hippocampal Synaptic
Plasticity.
AB - Special AT-rich sequence-binding protein 2 (Satb2) is a protein binding to the
matrix attachment regions of DNA and important for gene regulation. Patients with
SATB2 mutation usually suffer moderate to severe mental retardation. However, the
mechanisms for the defects of intellectual activities in patients with SATB2
mutation are largely unclear. Here we established the heterozygous Satb2 mutant
mice and Satb2 conditional knockout mice to mimic the patients with SATB2
mutation and figured out the role of Satb2 in mental activities. We found that
the spatial memory and working memory were significantly damaged in the
heterozygous Satb2 mutant mice, early postnatal Satb2-deficient mice (CaMKIIalpha
Cre+Satb2fl/fl mice), and adult Satb2 ablation mice (Satb2fl/fl mice injected
with CaMKIIalpha-Cre virus). Functionally, late phase long-term potentiation (L
LTP) in these Satb2 mutant mice was greatly impaired. Morphologically, in CA1
neurons of CaMKIIalpha-Cre+Satb2fl/fl mice, we found decreased spine density of
the basal dendrites and less branches of apical dendrites that extended into
lacunar molecular layer. Mechanistically, expression levels of immediate early
genes (IEGs) including Fos, FosB, and Egr1 were significantly decreased after
Satb2 deletion. And, Satb2 could regulate expression of FosB by binding to the
promoter of FosB directly. In general, our study uncovers that Satb2 plays an
important role in spatial memory and working memory by regulating IEGs-mediated
hippocampal synaptic plasticity.
PMID- 28421536
TI - Lysosomal Quality Control in Prion Diseases.
AB - Prion diseases are transmissible, familial or sporadic. The prion protein (PrP),
a normal cell surface glycoprotein, is ubiquitously expressed throughout the
body. While loss of function of PrP does not elicit apparent phenotypes,
generation of misfolded forms of the protein or its aberrant metabolic isoforms
has been implicated in a number of neurodegenerative disorders such as scrapie,
kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Straussler
Scheinker and bovine spongiform encephalopathy. These diseases are all
phenotypically characterised by spongiform vacuolation of the adult brain, hence
collectively termed as late-onset spongiform neurodegeneration. Misfolded form of
PrP (PrPSc) and one of its abnormal metabolic isoforms (the transmembrane CtmPrP)
are known to be disease-causing agents that lead to progressive loss of structure
or function of neurons culminating in neuronal death. The aberrant forms of PrP
utilise and manipulate the various intracellular quality control mechanisms
during pathogenesis of these diseases. Amongst these, the lysosomal quality
control machinery emerges as one of the primary targets exploited by the disease
causing isoforms of PrP. The autophagosomal-lysosomal degradation pathway is
adversely affected in multiple ways in prion diseases and may hence be regarded
as an important modulator of neurodegeneration. Some of the ESCRT pathway
proteins have also been shown to be involved in the manifestation of disease
phenotype. This review discusses the significance of the lysosomal quality
control pathway in affecting transmissible and familial types of prion diseases.
PMID- 28421538
TI - Roles of Nitric Oxide Synthase Isoforms in Neurogenesis.
AB - Nitric oxide (NO), a free radical gas, acts as a neurotransmitter or
neuromodulator in the central nervous system (CNS). It has been widely explored
as a mediator of neuroinflammation, neuronal damages, and neurodegeneration at
its pathological levels. Recently, increasing evidence suggests that NO plays key
roles in mediating adult neurogenesis, the process of neural stem cells (NSCs) to
generate newborn neurons for replacing damaged neurons or maintaining the
function of the brain. NO synthase (NOS) is a major enzyme catalyzing the
generation of NO in the brain. Recent studies indicate that three homologous NOS
isoforms are involved in the proliferation of NSCs and neurogenesis. Therefore,
the impact of NOS isoforms on NSC functions needs to be elucidated. Here, we
summarize the studies on the role of NO and NOS with different isoforms in NSC
proliferation and neurogenesis with the focus on introducing action mechanisms
involved in the regulation of NSC function. This growing research area provides
the new insight into controlling NSC function via regulating NO microenvironment
in the brain. It also provides the evidence on targeting NOS for the treatment of
brain diseases.
PMID- 28421539
TI - alpha-Synuclein Aggregates with beta-Amyloid or Tau in Human Red Blood Cells:
Correlation with Antioxidant Capability and Physical Exercise in Human Healthy
Subjects.
AB - Neurodegenerative disorders (NDs) are characterized by abnormal
accumulation/misfolding of specific proteins, primarily alpha-synuclein (alpha
syn), beta-amyloid1-42 (Abeta), and tau, in both brain and peripheral tissue. In
addition to homo-oligomers, the role of alpha-syn interactions with Abeta or tau
has gradually emerged. The altered protein accumulation has been related to both
oxidative stress and physical activity; nevertheless, no correlation among the
presence of peripheral alpha-syn hetero-aggregates, antioxidant capacity, and
physical exercise has been discovered as of yet. Herein, the content of alpha
syn, Abeta, tau, and of their heterocomplexes was determined in red blood cells
(RBCs) of healthy subjects (sedentary and athletes). Such parameters were related
to the extent of the antioxidant capability (AOC), a key marker of oxidative
stress in aging-related pathologies, and to physical exercise, which is known to
play an important preventive role in NDs and to modulate oxidative stress. Tau
content and plasma AOC toward hydroxyl radicals were both reduced in older or
sedentary subjects; in contrast, alpha-syn and Abeta accumulated in elderly
subjects and showed an inverse correlation with both hydroxyl AOC and the level
of physical activity. For the first time, alpha-syn heterocomplexes with Abeta or
tau were quantified and demonstrated to be inversely related to hydroxyl AOC.
Furthermore, alpha-syn/Abeta aggregates were significantly reduced in athletes
and inversely correlated with physical activity level, independent of age. The
positive correlation between antioxidant capability/physical activity and reduced
protein accumulation was confirmed by these data and suggested that peripheral
alpha-syn heterocomplexes may represent new indicators of ND-related protein
misfolding.
PMID- 28421540
TI - Maternal Folic Acid Supplementation During Pregnancy Improves Neurobehavioral
Development in Rat Offspring.
AB - Maternal folate status during pregnancy may influence central nervous system
(CNS) development in offspring. However, the recommended intakes of folic acid
for women of childbearing age differ among countries and there is still no
consensus about whether folic acid should be supplemented continuously throughout
pregnancy. We hypothesized that folic acid supplementation may be more beneficial
for offspring's neurobehavioral development if prolonged throughout pregnancy
instead of being limited to the periconceptional period. In this study, three
groups of the female rats were fed folate-normal, folate-deficient, or folate
supplemented diets throughout pregnancy. In another group, the female rats were
fed folate-supplemented diet from mating for 10 consecutive days and then fed
folate-normal diet for remainder days of pregnancy. The results showed that
maternal folate deficiency increased plasma homocysteine (Hcy) concentration in
dams, delayed early sensory-motor reflex development, impaired spatial learning
and memory ability, and caused ultrastructural damages in the hippocampus of
offspring. Maternal folic acid supplementation would be more effective on
improving early sensory-motor reflex development and spatial learning and memory
ability in offspring if prolonged throughout pregnancy instead of being limited
to the periconceptional period. In conclusion, prolonged maternal folic acid
supplementation throughout pregnancy would be more effective in neurobehavioral
development of offspring in rats.
PMID- 28421541
TI - Systemic Inflammation as a Driver of Brain Injury: the Astrocyte as an Emerging
Player.
AB - Severe systemic inflammation has strong effects on brain functions, promoting
permanent neurocognitive dysfunction and high mortality rates. Additionally,
hippocampal damage seems to be directly involved in this process and astrocytes
play an important role in neuroinflammation and in the neuroimmune response.
However, the contribution of the astrocytes to the pathology of acute brain
dysfunction is not well understood. Recently, our group established a protocol
for obtaining astrocyte cultures from mature brain to allow the characterization
of these cells and their functions under pathologic conditions. The present study
was designed to characterize astrocyte function after acute systemic inflammation
induced by cecal ligation and perforation (CLP). Hippocampal astrocyte cultures
from CLP animals presented increased levels of tumor necrosis factor-alpha (TNF
alpha), interleukin (IL)-1beta, IL-6, IL-18, and cyclooxygenase-2 and decreased
levels of IL-10. This proinflammatory profile was accompanied by an increase in
Toll-like receptor (TLR)2 mRNA expression levels and no change either in TLR4 or
in vascular endothelial growth factor (VEGF) gene expression. These alterations
were associated with increased expressions of p21, nuclear factor kappa B
(NFkappaB), and inducible nitric oxide synthase (iNOS) in astrocytes from CLP
animals. The same parameters were also evaluated in whole hippocampal tissue, but
differences in this profile were found compared to hippocampal astrocyte cultures
from CLP, reflecting an interaction between other central nervous system cell
types, which may mask specific astrocytic changes. These results improve our
understanding of the mechanisms by which astrocytes react against systemic
inflammation, and suggest these cells to be potential targets for therapeutic
modulation.
PMID- 28421543
TI - Changing and partially successful local institutions for harvest of thatch palm
leaves.
AB - In some cases, users of common-pool resources (CPR) successfully govern and
manage these for collective benefit but in other cases they fail to do so. When
evaluating the success of local institutions for CPR management, however,
researchers have not always clearly distinguished between success in terms of
compliance and endurance, and success in terms of the socio-economic and
environmental outcomes of the management. This study focused on the governance
and management of wayuri palms (Pholidostachys synanthera robusta), whose leaves
are harvested for roof thatch, in Ecuadorian Amazonia. Combining ethnographic
methods with field botanic inventory, it was shown that although local
institutions regulating leaf harvest had existed for longer than living memory,
and the degree of compliance was high, they did not prevent exhaustion of the
resource base, only delayed it.
PMID- 28421542
TI - Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic
Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.
AB - Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral
deficits. Previous evidences have suggested that neural stem cell (NSC)
transplantation could facilitate functional recovery from brain insults, but
their underlying mechanisms remains to be elucidated. Here, we established TBI
model by an electromagnetic-controlled cortical impact device in the rats. Then,
5 MUl NSCs (5.0 * 105/MUl), derived from green fluorescent protein (GFP)
transgenic mouse, was transplanted into the traumatic brain regions of rats at 24
h after injury. After differentiation of the NSCs was determined using
immunohistochemistry, neurological severity scores (NSS) and rotarod test were
conducted to detect the neurological behavior. Western blot and RT-PCR as well as
ELASA were used to evaluate the expression of synaptophysin and brain-derived
neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural
recovery after NSC transplantation, BDNF knockdown in NSC was performed and
transplanted into the rats with TBI, and potential mechanism for BDNF knockdown
in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody
blockade was conducted to further confirm the effect of BDNF on neural activity.
As a result, an increasing neurological function improvement was seen in NSC
transplanted rats, which was associated with the upregulation of synaptophysin
and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF
antibody block reduced not only the level of synaptophysin but also exacerbated
neurological function deficits. Microassay analysis showed that 14 genes such as
Wnt and Gsk3-beta were downregulated after BDNF knockdown. The present data
therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC
transplantation for the treatment of TBI in adult rats.
PMID- 28421545
TI - The association between the time from oxytocin cessation during labour to
Cesarean delivery and postpartum blood loss: a retrospective cohort study.
AB - PURPOSE: Prolonged exposure to oxytocin during augmentation of labour is
associated with uterine atony and an increased risk of postpartum hemorrhage
(PPH) due to oxytocin receptor desensitization. Cessation of oxytocin infusion
during labour may facilitate recovery of oxytocin receptor function, which then
helps to restore myometrial contractility and decrease postpartum blood loss. We
examined the association between oxytocin recovery interval, i.e., the time from
discontinuing oxytocin to Cesarean delivery (CD) for labour arrest, and blood
loss. METHODS: This retrospective cohort study included women who underwent CD
for labour arrest following oxytocin-augmented labour from July 1, 2013 to July
19, 2015 at our institution. Data were collected on patient demographics, labour
and delivery characteristics, oxytocin induction and augmentation, recovery
interval, and PPH risk factors. The primary outcome was estimated blood loss
(EBL), calculated using the hematocrit variation method. RESULTS: Data on 490
women were analyzed. The mean (standard deviation) EBL was 1,341 (577) mL; the
amount of oxytocin administered during labour was 6,447 (6,868) mU, and the
oxytocin recovery interval was 99 (65) min. Every ten-minute increase in the
recovery interval was associated with a 10-mL decrease in EBL (95% confidence
interval [CI], -18 to -3; P = 0.009). Morbidly obese women had a significantly
higher EBL than those with a body mass index < 40 kg.m-2 (mean difference, 572
mL; 95% CI, 382 to 762; P < 0.001). The amount and duration of oxytocin
administered during labour, but not the oxytocin recovery interval, was
associated with the use of additional interventions to control PPH (P = 0.005).
CONCLUSION: Our study shows that an increase in the oxytocin recovery interval is
associated with a decrease in blood loss at CD in women with oxytocin augmented
labour. These data support discontinuing the oxytocin infusion as soon as the
decision is made to proceed with CD for labour arrest, particularly in morbidly
obese women.
PMID- 28421546
TI - Electronic medical record interventions and recurrent perioperative antibiotic
administration: a before-and-after study.
AB - PURPOSE: Perioperative antibiotics decrease rates of surgical-site infections.
Numerous interventions have improved administration of the first antibiotic dose;
however, failures in the administration of subsequent doses frequently occur. We
hypothesized that modifications to the electronic medical record (EMR) would
improve the administration of the second antibiotic dose and that such
improvements would be sustained over time. METHODS: This historical cohort before
and-after study of multipronged alerts in the EMR analyzed 1,348 operations on
adult patients. The operations lasted >= 240 min, utilized cefazolin as the
perioperative antibiotic-constituting 1,348 second and 182 third intraoperative
antibiotic doses-and did not involve cardiopulmonary bypass. A decision support
intervention provided dosing recommendations when clinicians documented
antibiotics. The reminder intervention displayed a continuous bar in the EMR,
starting at the time the antibiotics were dosed and ending 15 min before
subsequent doses were indicated. The primary endpoints of the study were the
change in the proportion of correctly administered second dose of cefazolin,
given in accordance with hospital guidelines in the month after implementing the
intervention, and whether any improvements declined by three to seven months
after implementation. RESULTS: Pre-intervention, 51.4% of second doses of
cefazolin were correctly administered. In the immediate post-intervention period,
68.5% were correctly administered, representing a significant absolute
improvement of 17.1% (95% confidence interval, 8.1 to 26.1; P < 0.001). Rates did
not decline over time; clinicians correctly administered 73.3% of doses in the
delayed post-intervention period (P < 0.001 vs pre-intervention). CONCLUSIONS:
These inexpensive nonintrusive interventions to the EMR provided modest lasting
improvements in proper administration of repeated doses of cefazolin. The fact
that only approximately 70% compliance was reached highlights the difficulty in
addressing this deficiency.
PMID- 28421547
TI - Effect of health literacy on adherence to osteoporosis treatment among patients
with distal radius fracture.
AB - : Patients with inadequate health literacy, those with medical comorbidities, or
those with a previous history of adverse drug events have a higher likelihood of
non-adherence to osteoporosis treatment after sustaining a distal radius
fracture. INTRODUCTION: Patients with a distal radial fracture (DRF) have a
higher risk of subsequent fractures, which provides an important opportunity to
begin treatment for osteoporosis. This study assessed the effect that health
literacy of patients suffering from a DRF has on the subsequent adherence to
osteoporosis treatment. METHODS: A total of 116 patients (female, over 50 years
of age) presenting a DRF caused by low-energy trauma were enrolled. Their health
literacy was measured using the Newest Vital Sign (NVS). Alendronate (70 mg,
orally, once weekly) was prescribed to all patients for 1 year, and adherence was
defined as taking at least 80% of the tablets for 12 months and returning for the
visit on month 12. Multivariable analyses were conducted to determine whether the
patients' clinical, demographic, and health literacy factors influenced their
adherence to osteoporosis treatment. RESULTS: About half (52%) of the
participants who sustained a DRF exhibited an inadequate health literacy, and the
rate of non-adherence to osteoporosis treatment was 38%. The rate of non
adherence for patients with inadequate literacy was significantly higher than for
those with appropriate literacy (47 vs. 29%, p = 0.04). The results of the
regression analysis indicate that limited health literacy, the presence of
comorbidities, and prior history of adverse drug events are associated with a
higher likelihood of non-adherence to osteoporosis treatment after sustaining a
DRF. CONCLUSIONS: Patients with inadequate health literacy, adverse drug events,
or medical comorbidities had higher rates of non-adherence with alendronate
treatment after sustaining a DRF. Further research is needed to show whether
improvements in patient comprehension via informational intervention in patients
with a DRF will improve adherence to osteoporosis treatment.
PMID- 28421548
TI - Erratum to: A database of body-only computer-generated pictures of women for body
image studies: Development and preliminary validation.
PMID- 28421549
TI - Extragastrointestinal stromal tumor of the inferior vena cava: a case report.
AB - Here, we present a case report of a 60-year-old female with a 5-cm tumor in the
inferior vena cava (IVC) that was positive for c-kit and CD34 expression. Thus,
we considered this to be an extragastrointestinal c-kit-positive stromal tumor
(EGIST). To the best of our knowledge, no primary EGISTs of the IVC have been
described thus far. The potential occurrence of EGISTs outside the tubular
gastrointestinal tract should be recognized in the differential diagnosis of
tumors of the great vessels. Thus, we concluded that primary c-kit-positive
stromal tumors of the IVC do indeed occur.
PMID- 28421550
TI - Distribution, genetic diversity and potential spatiotemporal scale of alien gene
flow in crop wild relatives of rice (Oryza spp.) in Colombia.
AB - BACKGROUND: Crop wild relatives (CWRs) of rice hold important traits that can
contribute to enhancing the ability of cultivated rice (Oryza sativa and O.
glaberrima) to produce higher yields, cope with the effects of climate change,
and resist attacks of pests and diseases, among others. However, the genetic
resources of these species remain dramatically understudied, putting at risk
their future availability from in situ and ex situ sources. Here we assess the
distribution of genetic diversity of the four rice CWRs known to occur in
Colombia (O. glumaepatula, O. alta, O. grandiglumis, and O. latifolia).
Furthermore, we estimated the degree of overlap between areas with suitable
habitat for cultivated and wild rice, both under current and predicted future
climate conditions to assess the potential spatiotemporal scale of potential gene
flow from GM rice to its CWRs. RESULTS: Our findings suggest that part of the
observed genetic diversity and structure, at least of the most exhaustively
sampled species, may be explained by their glacial and post-glacial range
dynamics. Furthermore, in assessing the expected impact of climate change and the
potential spatiotemporal scale of gene flow between populations of CWRs and GM
rice we find significant overlap between present and future suitable areas for
cultivated rice and its four CWRs. Climate change is expected to have relatively
limited negative effects on the rice CWRs, with three species showing
opportunities to expand their distribution ranges in the future. CONCLUSIONS:
Given (i) the sparse presence of CWR populations in protected areas (ii) the
strong suitability overlap between cultivated rice and its four CWRs; and (iii)
the complexity of managing and regulating areas to prevent alien gene flow, the
first priority should be to establish representative ex situ collections for all
CWR species, which currently do not exist. In the absence of studies under field
conditions on the scale and extent of gene flow between cultivated rice and its
Colombian CWRs, effective in situ conservation might best be achieved through
tailor-made management plans and exclusion of GM rice cultivation in areas
holding the most genetically diverse CWR populations. This may be combined with
assisted migration of populations to suitable areas where rice is unlikely to be
cultivated under current and future climate conditions.
PMID- 28421551
TI - Macrolides, Digoxin Toxicity and the Risk of Sudden Death: A Population-Based
Study.
AB - INTRODUCTION: Digoxin is commonly prescribed to elderly patients with heart
failure and atrial fibrillation, and macrolide antibiotics markedly increase the
risk of digoxin toxicity. OBJECTIVE: The aim was to determine whether, in older
patients receiving digoxin, macrolide antibiotics are associated with sudden
death. METHODS: We used a population-based, nested, case-control design from
January 1, 1994 to December 31, 2012 in a cohort of Ontario residents aged 66
years or older prescribed digoxin. The primary outcome was the risk of sudden
death within 14 days of exposure to one of three antibiotics (erythromycin,
clarithromycin, or azithromycin), relative to cefuroxime. RESULTS: Among 39,072
Ontarians who died suddenly while receiving digoxin, 586 died within 14 days of
receiving a study antibiotic. Relative to cefuroxime, we found no statistically
significant increase in the risk of sudden death following treatment with
erythromycin [adjusted odds ratio (aOR) 0.98; 95% confidence interval (CI) 0.65
1.48], clarithromycin (aOR 1.25; 95% CI 0.94-1.65), or azithromycin (aOR 1.07;
95% CI 0.75-1.53). CONCLUSION: This finding reinforces the cardiovascular safety
of macrolide antibiotics in a high-risk population.
PMID- 28421552
TI - Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule
Cell Layer.
AB - Local field potential (LFP) oscillations in the granule cell layer (GCL) of the
cerebellar cortex have been identified previously in the awake rat and monkey
during immobility. These low-frequency oscillations are thought to be generated
through local circuit interactions between Golgi cells and granule cells within
the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also
are electrically coupled through gap junctions within the GCL. Here, we tested if
gap junctions in the rat cerebellar cortex contribute to the generation of LFP
oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia,
and examined the effects of local infusion of gap junction blockers on 5-15 Hz
oscillations. Local infusion of the gap junction blockers carbenoxolone and
mefloquine resulted in significant decreases in the power of oscillations over a
30-min period, but the power of oscillations was unchanged in control experiments
following vehicle injections. In addition, infusion of gap junction blockers had
no significant effect on multi-unit activity, suggesting that the attenuation of
low-frequency oscillations was likely due to reductions in electrical coupling
rather than a decreased excitability within the granule cell layer. Our results
indicate that electrical coupling among the Golgi cell networks in the cerebellar
cortex contributes to the local circuit mechanisms that promote the occurrence of
GCL LFP slow oscillations in the anesthetized rat.
PMID- 28421553
TI - Microwave ablation of malignant renal tumours: intermediate-term results and
usefulness of RENAL and mRENAL scores for predicting outcomes and complications.
AB - The aim of this study was to evaluate intermediate-term results after microwave
ablation (MWA) of renal tumours and determine the association of RENAL and
modified RENAL (mRENAL) scores with oncological outcomes and complications. In
May 2008-September 2014, 58 patients affected by early-stage RCC (renal cell
carcinoma; T1a or T1b) were judged unsuitable for surgery and treated with
percutaneous MWA. Follow-up was performed with contrast-enhanced computed
tomography at 1, 3, 6, 12 and 24 months after the procedure. Technical success
(TS), primary technical effectiveness (PTE), secondary technical effectiveness
(STE), the local tumour progression rate (LTPR), the cancer-specific survival
rate (CSSR), disease-free survival (DFS), overall survival (OS) and safety were
recorded. All lesions were evaluated using RENAL and mRENAL scores, and
complications were assessed with RENAL scores. The TS rate was 100%, PTE was 93%,
STE was 100%, LTPR was 15.7% at 1 year, CSSR was 96.5%, DFS was 87.9% at 5 years,
and OS was 80.6%. Mean follow-up was 25.7 months (range 3-72). The mean +/-
standard deviation (SD) RENAL and mRENAL scores of all treated tumours were 6.7
+/- 2.05 (range 4-11) and 7 +/- 2.3 (range 4-12), respectively. Major
complications occurred in two (2/58) and minor complications in three patients
(3/58). Overall complications correlated significantly with RENAL scores; in
particular, E and L represent negative predictors for safety and effectiveness.
MWA is a valuable alternative for treating RCCs. The correlation with outcomes
and complications of RENAL and mRENAL scores could help to customise MWA
indications in RCC patients.
PMID- 28421554
TI - Drug Therapy in the 1990s : What Can We Expect for Cystic Fibrosis?
PMID- 28421557
TI - Cancer-Associated Anorexia and Cachexia : Implications for Drug Therapy.
AB - Anorexia and cachexia are major problems in patients with cancer. Such measures
as anticancer therapy, dietary counselling or hyperalimentation are not very
successful in reversing this phenomenon in the vast majority of cancer patients.
Thus, several drugs have been evaluated as agents to ameliorate cancer-associated
anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to
cause slight appetite stimulation in patients. A randomised clinical trial,
however, was unable to demonstrate any weight gain from this agent.
Corticosteroids are frequently used in clinical practice for appetite stimulation
in patients with advanced malignancies. Supporting this practice, 4 randomised
clinical trials showed that corticosteroid medications can stimulate the
appetites of advanced cancer patients. However, these studies were not able to
show any substantial nonfluid weight gain in treated patients.Megestrol acetate
is a progestational agent which appears to be a relatively potent appetite
stimulant. Randomised studies in advanced cancer patients have shown both
substantial appetite stimulation and improvement in the nonfluid bodyweights of
patients receiving this drug. Preliminary evidence also suggests that this drug
has antiemetic properties. Several clinical studies are currently ongoing to
determine the effect of various doses of megestrol acetate in patients with
cancer.Efforts are also ongoing to evaluate both anabolic steroids and hydrazine
sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The
preliminary nature of these investigations, however, precludes recommendations
for the use of either of these latter 2 drugs in routine clinical practice.
PMID- 28421556
TI - Recent Advances in Pharmacological Management of Hypertension in Diabetic
Patients with Nephropathy : Effects of Antihypertensive Drugs on Kidney Function
and Insulin Sensitivity.
AB - Hypertension is often seen in Type 1 and Type 2 diabetic patients, particularly
in those with nephropathy, and the progression of diabetic nephropathy is closely
related to blood pressure elevation. Thus, the effects of antihypertensive drugs
on kidney function and insulin sensitivity in diabetic patients are of great
clinical importance.Successful antihypertensive treatment has been shown to slow
the progression of diabetic nephropathy. Several results from short term studies
have suggested that angiotensin converting enzyme (ACE) inhibitors may be
advantageous over other conventional antihypertensive agents in reducing
albuminuria in both hypertensive and normotensive diabetics with microalbuminuria
or persistent proteinuria. However, the decline in glomerular filtration rate
during ACE inhibitor treatment is comparable to that during effective treatment
with conventional antihypertensive drugs in hypertensive Type 1 diabetic patients
with overt nephropathy. Whether ACE inhibitors possess a specific effect in
preventing the development of diabetic nephropathy remains to be seen in properly
designed long term studies. Although calcium antagonists may preserve kidney
function or possess a renoprotective effect in hypertensive Type 2 diabetics with
nephropathy, firm evidence supporting this contention seems to be lacking and
also requires long term evaluation.Increasing attention is being directed toward
the effect of antihypertensive drugs on insulin sensitivity in diabetic patients:
ACE inhibitors and alpha-adrenoceptor blocking agents have been shown to improve
this sensitivity. Despite the widespread involvement of calcium in hormone
secretion and action, calcium antagonists appear to have little effects on the
glucoregulatory and calcium-regulatory hormones within the drug dosages used in
clinical practice.Several clinical variables, such as the presence or absence of
hypertension, overt nephropathy and microalbuminuria, or a combination of
variables should be accounted for when evaluating critically the cumulative data
on the effects of antihypertensive drugs on kidney function and albuminuria in
the variety of diabetic patient groups. Understanding the pharmacokinetic and
pharmacodynamic characteristics of antihypertensive drugs will be of clinical
importance in diabetic patients with advanced nephropathy (glomerular filtration
rate of < 30 ml/min) and/or other complications, such as impaired gastric
motility or gastroparesis, and will thereby lead to a more rational management of
hypertension in those patients.
PMID- 28421555
TI - Pharmacological Agents Affecting Emesis : A Review (Part II).
AB - Part I of this article reviewed the pathophysiology of emesis, and its
pharmacological treatment. Drug-induced vomiting was also discussed. In the
second part of the review, other common causes of vomiting are considered.The
basis of the use of antiemetics in morning sickness and migraine is still
obscure; for the latter, serotonin 5-HT1 receptor agonists, 5-HT3 receptor
antagonists and dopamine D2 receptor antagonists are effective. For motion
sickness, control can be achieved with various antagonists of muscarinic or
histamine H1-receptors. Centrally active adrenoceptor agonists in combination
with a muscarinic antagonist or H1-receptor antagonist may offer better control
of motion sickness and its associated symptoms than either antagonist alone;
based on clinical studies, post-operative vomiting after opiate administration
appears to be controlled by blocking dopamine D2, histamine H1-or muscarinic
receptors.Radiation therapy appears to be similar to cytotoxic therapy in that
the mediators produced or released by radiation activate both peripheral and
central sites involved in the vomiting reflex. Blockade of dopamine D2 and 5-HT3
receptors may be effective.
PMID- 28421561
TI - A New Mexican Species of Orizabus Fairmaire (Coleoptera: Scarabaeidae:
Dynastinae: Pentodontini), with a Key to the Species of the Genus.
AB - A new Orizabus species is described from Chilapa de Alvarez in the state of
Guerrero (Mexico). The new species is similar to Orizabus rawlinsi Dechambre Bull
Soc Entomol Fr 98:342, 1993, which is known from the state of Oaxaca but differs
in the pygidial punctation, and the shape of the marginal pronotal bead and the
parameres. A revised identification key to Orizabus species is provided.
PMID- 28421560
TI - Acitretin : A Review of its Pharmacology and Therapeutic Use.
AB - SYNOPSIS: Acitretin (etretin), a second generation monoaromatic retinoid for use
in the treatment of severe psoriasis and other dermatoses, is the major active
metabolite of etretinate and possesses a similar therapeutic index; i.e. a
similar ratio of clinical efficacy to adverse effects. When used alone at a
maintenance dosage of 30 to 50mg daily, acitretin is effective in the treatment
of psoriasis, causing a reduction in the severity of scaling, erythema and
induration. Efficacy appears to be further enhanced by combination with psoralen
ultraviolet A photochemotherapy (PUVA) or ultraviolet B irradiation (UVB). These
combinations reduce the time to lesion clearance and reduce the total radiation
dose, improving overall safety. Comparative studies have confirmed the
equivalence of acitretin and etretinate with regard to efficacy and toxicity.
Adverse reactions are dose-related and generally typical of hypervitaminosis A.
Alopecia and mucocutaneous symptoms such as cheilitis and drying of the mucous
membranes are particularly prevalent. Hypertriglyceridaemia and elevation of
cholesterol levels also occur. Examination of the pharmacokinetic profile of
acitretin reveals its main advantage over etretinate. Acitretin is less
lipophilic than etretinate, and its lack of sequestration into 'deep' fatty
storage sites is reflected in a comparatively short terminal elimination half
life of 50 to 60 hours, compared with 120 days for etretinate. Due to its
teratogenic potential, acitretin is strictly contraindicated in women of
childbearing potential unless effective contraceptive measures are employed.
Etretinate has been identified in plasma samples of some patients treated with
acitretin. Thus, acetretin has an established place in the treatment of
keratinising disorders, although its use in women of child-bearing potential must
be accompanied by effective contraceptive measures, with a further 2-year
contraceptive period after therapy completion. PHARMACODYNAMIC PROPERTIES:
Investigation of the pharmacodynamic properties of acitretin has been restricted
to some extent by the lack of a suitable experimental model. While in vitro
results using normal human skin fibroblasts have been conflicting, acitretin
generally modulates cell proliferation in cultures from hyperproliferative
conditions such as psoriasis or neoplasia, and inhibits epidermal cell growth and
differentiation. Acitretin also inhibits chemically induced hyperplasia, and
causes regression or inhibits further growth and development of a number of
established or transplantable carcinoma cell lines. The mechanism of action of
acitretin in hyperproliferative disorders has yet to be fully elucidated;
however, there appear to be a number of cellular effects. Target receptor site
candidates include the cellular retinoic acid binding protein (CRABP), the
epidermal growth factor (EGF) receptor, and retinoic acid nuclear receptors
(RARs). Acitretin binds competitively to CRABP, a protein present in high
concentrations in psoriatic plaques, and induces a marked elevation of CRABP
levels in normal epidermis. However, 13-cis-acitretin does not bind to CRABP and
acitretin may act via activation of RARs following conversion to a substance
which binds to these receptors. In addition, the EGF receptor may be involved
since acitretin has been found to influence its normal modulation of cell growth
in both normal fibroblasts and squamous carcinoma cell lines. Cyclic adenosine
monophosphate (cAMP)-dependent protein kinases and ornithine decarboxylase are
probable mediators of the clinical response. In addition, acitretin demonstrates
immunomodulatory and anti-inflammatory effects. It is hypothesised that the
mechanisms entail inhibition of polymorphonuclear leucocyte accumulation in the
stratum corneum, inhibition of lymphocytic blastogenesis by mitogens and
stimulation of T cell-mediated cytotoxicity. PHARMACOKINETIC STUDIES: Following
oral administration of the drug to patients with psoriasis, peak plasma acitretin
concentrations range from 98 to 526 ug/L and are reached approximately 1.9 hours
after a single 40mg dose. Acitretin is widely distributed in the body and
systemic bioavailability is approximately 60%. It is extensively bound to albumin
and has a high affinity for CRABP. Less than 5% of acitretin is bound to
lipoproteins and this is reflected in its comparative lack of sequestration into
fatty 'deep' storage sites and its short terminal elimination half-life relative
to etretinate. Multiple dose studies have indicated an elimination half-life of
50 to 60 hours, and neither acitretin nor its isomeric counterpart, 13-cis
acitretin, is detectable in plasma 3 to 4 weeks after cessation of long term
therapy. Isomeric interconversion is prevalent following oral administration of
acitretin: mean maximum plasma concentrations of the 13-cis-isomeric metabolite
are lower and occur slightly later than with acitretin. Plasma trough
concentrations of this metabolite following long term administration of acitretin
are about 5 times higher than those of the parent drug and the terminal
elimination half-life is about 15 times longer. Acitretin is excreted
predominantly via the renal and hepatic routes, as glucuronides in bile or as
products with shortened side chains in urine. In blood, 13-cis-acitretin and 3
other metabolites have been identified. Liquid chromatography/mass spectroscopy
has identified etretinate in plasma samples of some patients treated with
acitretin. The results obtained so far are of concern with regard to a potential
teratogenic effect in female patients. Therefore, an increase in the post therapy
contraception period to 2 years instead of the 2 months previously advocated is
appropriate until clarification of these recent results have been obtained.
THERAPEUTIC EFFICACY: Trials with an initial double-blind phase and a subsequent
noncomparative phase of up to 6 months duration have demonstrated the efficacy of
orally administered acitretin (generally 25 to 75 mg/day) in the treatment of
severe psoriasis. Variants of psoriasis vulgaris are notably susceptible to
treatment and acitretin also appears to be effective against severe forms of
pustular and erythrodermic psoriasis. Preliminary studies in small patient
populations and a number of individual case reports suggest that acitretin, 30 to
50 mg/day, is beneficial in a variety of other cutaneous disorders including
Darier's disease, lupus erythematosus and severe recessive x-linked ichthyosis.
The rarity of these conditions prevents adequate extensive trials. Double
blinding in placebo-controlled trials is difficult to maintain due to the
ubiquitous and distinctive nature of acitretin-induced adverse effects. However,
double-blinding strategies have been used effectively in studies in which a dose
finding phase preceded a longer term noncomparative phase. Subjective assessments
have revealed good to excellent (? 50%) clearance of severe psoriasis in > 75% of
patients: the severity of scaling, erythema and epidermal induration, and the
percentage of body surface involvement, are reduced. Comparative studies in
patients with psoriasis indicate that acitretin is comparable with etretinate in
terms of therapeutic efficacy and adverse effects. When acitretin is combined
with psoralen-ultraviolet A photochemotherapy (PUVA), clinical efficacy is
improved, as evidenced by a higher complete remission rate and a reduced time to
clearance of psoriasis. Total irradiation requirement is also reduced. Similar
results are also achieved when acitretin is combined with ultraviolet B
irradiation. ADVERSE EFFECTS: Acitretin therapy has distinctive adverse effects
generally typical of hypervitaminosis A. While the incidence of mucocutaneous
clinical adverse effects is high, their severity does not usually necessitate
withdrawal of therapy, and they are completely reversed on cessation of
treatment. Adverse effects are usually dose-related, although alopecia is also
dependent on the duration of therapy. Mucocutaneous reactions are most common -
drying of mucous membranes of the eyes, nose and lips, and cheilitis occurs in
nearly all patients. Other clinical symptoms include alopecia, desquamation of
the skin, pruritus and 'sticky' skin. Changes in the lipid profile are often
observed. Hypertriglyceridaemia occurs in 35% of patients treated with acitretin
50 mg/day, but increases in serum cholesterol are less frequently reported. Liver
enzyme levels are also adversely affected, hepatitis has been reported and
acitretin therapy may have an adverse effect on bone. As with etretinate,
acitretin is a potent teratogen. DOSAGE AND ADMINISTRATION: Initial acitretin
dosage has usually ranged from 10 to 75 mg/day orally. After a few weeks, the
dose should be individually adjusted to obtain optimum therapeutic response with
tolerable adverse effects. Maintenance doses in such trials have ranged from 30
to 50 mg/day. Some authorities advocate low-dose therapy initially followed by a
progressive dosage increase. Because of its potent teratogenicity and the
detection of etretinate in patients treated with acitretin, the drug is
contraindicated in women of childbearing potential unless effective contraceptive
measures are adopted. It is essential that pregnancy be avoided for a full 2
years after therapy finishes, instead of the 2 months previously advocated.
PMID- 28421562
TI - Prevention of Bacterial Biofilm Formation on Soft Contact Lenses Using Natural
Compounds.
AB - PURPOSE: In eye care field, contact lenses (CL) have a great impact on improving
vision, but their use can be limited by ocular infection. CL- associated
infections can be reduced by good attention to CL storage case practice. CL-care
solutions should be able to control microbial growth on CL. The aim of the study
was to evaluate and compare the efficacy of CL-care solutions (found in Egyptian
market) with some natural compounds in removal and inhibition of bacterial
biofilm formed on soft CL. Clinical isolates were recovered from patients having
conjunctivitis from Benha University Hospital and identified microbiologically.
Quantification of biofilm was done using microtiter plate assay. Three
multipurpose CL-care solutions were examined for their ability to remove and
inhibit biofilm. Also four natural extracts having antibacterial activity and are
safe on eye were tested for their anti-biofilm activity. RESULTS: The major
bacterial isolates from eye infections were Pseudomonas aeruginosa (36%) and
Staphylococcus spp. (37.8%). Only 33.3% of isolates showed ability to produce
weak to moderate biofilm. The tested multi-purpose CL-care solutions showed
moderate ability to remove preformed biofilm. Among the tested natural compounds,
Calendula officinalis and Buddleja salviifolia extracts showed an excellent
efficacy in inhibition of biofilm and also removal of preformed biofilm.
CONCLUSION: This study demonstrated that isolates from infected eye and CL-cases
showed weak to moderate biofilm formation. Calendula officinalis and Buddleja
salviifolia extracts showed excellent effect on inhibition and removal of
biofilm, these extracts could be added into CL-care solutions which could
markedly reduce eye-infections during CL-wear.
PMID- 28421563
TI - The current utilization and perceptions of prescription drug monitoring programs
among emergency medicine providers in Florida.
AB - BACKGROUND: Pain is among the most commonly treated symptoms in the emergency
department, and opioids are commonly prescribed from the emergency department to
treat moderate to severe pain. Prescription drug monitoring programs (PDMP) can
be used to assist physicians identify individuals at increased risk to misuse or
abuse opioids. While the use of the PDMP has been shown useful among clinicians,
in the past, utilization of the PDMP has been less than optimal. The objective of
this study was to assess the current utilization and perceptions of the
prescription drug monitoring program among emergency medicine providers in
Florida. METHODS: A survey assessing the utilization and perception of Florida's
prescription drug monitoring program was distributed to emergency medicine
providers in Florida over a 5 week period. Attending physicians, physicians in
training, and extenders from a variety of practice types were assessed. RESULTS:
A total of 88 surveys were completed. Over two thirds (67%) of the respondents
were male. The majority of respondents were attending physicians (62%), 13 (14%)
were residents, and 21 (23%) were extenders. Nearly all (99%) were aware of
Electronic-Florida Online Reporting of Controlled Substance Evaluation Program
(EFORCSE) and 84% had registered accounts. More than 2/3 (73%) reported feeling
pressured to prescribe opioids, and 70% reported receiving no formal education on
identifying individuals at increased risk of opioid misuse. Approximately half
(51%) reported that they used EFORCSE only when they suspect the patient may
misuse the medication, 21% reported that they rarely used EFORCSE, and only 3%
reported using PDMP every time that they prescribed opioids. Residents used PDMP
less frequently than extenders and attending physicians. The most common barriers
associated with PDMP use were related to access. CONCLUSIONS: Although most
providers reported that they were aware of their states' PDMP, utilization of the
PDMP among emergency medicine providers in Florida remains low. Low utilization
was associated with barriers to access. If further enhancements to PDMPs can be
made to improve accessibility, then rates of PDMP utilization may increase.
PMID- 28421558
TI - Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF) : A Review
of its Pharmacological Properties and Prospective Role in the Management of
Myelosuppression.
AB - SYNOPSIS: Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)
is a polypeptide hormone produced through recombinant DNA technologies in
glycosylated (yeast or mammalian expression systems) or nonglycosylated
(Escherichia coli expression system) form. It is a multilineage haematopoietin
which stimulates proliferation and differentiation of bone marrow myeloid
progenitors and increases peripheral white blood cell counts when administered
systemically. Treatment is generally well tolerated, although mild to moderate
flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be
problematic in occasional patients. rGM-CSF accelerates recovery of peripheral
neutrophil counts after bone marrow transplantation, and results of a placebo
controlled randomised trial correlate this with reduced infectious episodes and
shortened length of hospitalisation in patients with lymphoid malignancies. A
substantial number of patients with graft failure after bone marrow
transplantation also respond to rGM-CSF. The duration of myelosuppression
secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which
has permitted investigation of antineoplastic dose-intensity escalation. In some
haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia
secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically
useful increases in peripheral blood granulocyte counts, although the effect is
generally not sustained after drug withdrawal. The potential for rGM-CSF to
stimulate proliferation of the abnormal clone in myelodysplasia and in acute
myelogenous leukaemia following induction therapy is of concern. Available data
suggest, however, that with appropriate monitoring and exclusion of high-risk
patients this serious potential risk can be avoided, and that myelopoiesis is
enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating
factors are a new therapeutic modality; hence many aspects of their use remain to
be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has
major potential in the management of myelosuppression secondary to cytoreductive
therapy with or without bone marrow transplantation, and in amelioration of
disturbed myelopoiesis. It represents an important application of biotechnology
to a difficult area of therapeutics. PHARMACOLOGICAL PROPERTIES: Endogenous GM
CSF is produced by T-lymphocytes, macrophages, fibroblasts and endothelial cells,
and participates both in the complex regulation of blood cell formation and in
activation of mature leucocytes. It is a polypeptide which is variably
glycosylated in its native state although the carbohydrate content is not
essential for its biological effects, and the 3 available recombinant forms
(which differ in extent of glycosylation) are similarly active in vivo.
Proliferative activity and priming of mature cells are manifest at similar
picomolar concentrations of GM-CSF, and it is the programming of the cell which
appears to determine the response to binding of GM-CSF to its cell surface
receptor. In concert with other colony-stimulating factors, GM-CSF facilitates
lineage commitment and subsequently supports or amplifies the clonogenic activity
of lineage-restricted factors, with the strongest effect seen on the granulocyte
macrophage lineage. A biphasic response was seen when rGM-CSF was administered in
doses up to 1000 ug/m2/day or 60 ug/kg/day by subcutaneous or intravenous routes
in phase I/II trials. Peripheral blood leucocyte counts decreased rapidly and
profoundly secondary to sequestration within the lungs. Re-entry of these cells
into the circulation restores counts to baseline in 2 to 4 hours and thereafter
an increase in the proliferative fraction of haematopoietic cells in bone marrow
probably accounts for the progressive rise in the number of neutrophils,
eosinophils and monocytes. This effect is dose-proportional. GM-CSF stimulates
proliferation of leukaemic progenitors from patients with acute myeloid leukaemia
without stimulating differentiation. In contrast, the abnormal clone from
myelodysplastic patients can be induced with GM-CSF to differentiate in vitro
although karyotype anomalies persist. In vitro studies suggest that stimulation
of nonhaematological cancer cells at physiological concentrations of GM-CSF is
unlikely. The priming effects of GM-CSF on mature leucocytes which include
increased expression of other cytokines, secretion of granule contents,
augmentation of antigen presentation, altered chemotaxis, and enhanced
phagocytosis, oxidative metabolism and antibody dependent cell-mediated
cytotoxicity probably serve to increase the host response to infection.
Administration of murine rGM-CSF to mice injected with lethal inocula of, for
example, Pseudomonas aeruginosa improved their survival relative to controls.
There are several reports of refractory infection in seriously ill neutropenic
patients resolving after addition of rGM-CSF to ongoing antimicrobial therapy and
subsequent neutrophil recovery; however, the role of rGM-CSF in management of
established infection in patients with neutropenia remains to be more thoroughly
investigated. The pharmacokinetic properties of rGM-CSF depend on the route of
administration. After intravenous administration, serum levels decline rapidly
with a half-life of distribution (t1/2alpha) of 5 to 15 minutes and half-life of
elimination (t1/2beta) of 1.5 to 2 hours. Maximum serum concentrations are
reached 2 hours after subcutaneous injection, then decline with a t1/2beta of 3
hours. Serum levels of rGM-CSF increase with dose and a proposed therapeutic
target level of 1 ug/L is maintained for 8 to 22 and 16 hours after
administration of 15 ug/kg of rGM-CSF by intravenous bolus and subcutaneous
injection, respectively. THERAPEUTIC USE: The correlation between duration and
severity of neutropenia and incidence of serious infection is well established.
Administration of rGM-CSF to bone marrow transplant recipients is aimed at
reducing morbidity in the early post-transplant period by shortening the duration
of agranulocytosis. Intravenous administration of rGM-CSF up to 16 ug/kg/day
(approximately 640 ug/m2/day) is well tolerated, and when begun within 24 hours
of autologous marrow infusion produces the earlier appearance of > 0.5 * 109/L
neutrophils in the peripheral circulation as compared with historical controls.
Early studies indicate that treated patients have a lower incidence of culture
proven bacteraemia, and recent reports, some preliminary, of placebo-controlled
and randomised trials confirm that patients with nonHodgkin's lymphoma or acute
lymphocytic leukaemia who receive rGM-CSF 250 ug/m2 by daily 2-hour infusion for
21 days or more post transplantation, have significant reductions in duration of
infectious episodes, antibiotic administration and hospitalisation. More limited
data support a similar acceleration of neutrophil recovery in allogeneic bone
marrow transplant recipients treated with rGM-CSF, with no apparent effect on the
incidence or severity of graft-versus-host disease. rGM-CSF is less effective in
patients in whom progenitor cell numbers are reduced by chemical purging of the
marrow whether administered immediately after marrow infusion or when used as
salvage therapy in patients with graft failure. A substantial proportion of
patients with failure of autologous or allogeneic bone marrow grafts respond to
prompt administration of rGM-CSF after diagnosis of graft failure, with an
increase in absolute neutrophil count and bone marrow cellularity. In 1 study of
37 such patients, overall survival was significantly improved compared with
historical controls. rGM-CSF increases the number of progenitor cells in
peripheral circulation and, either alone or in combination with cyclophosphamide,
facilitates the harvest of stem cells by apheresis for subsequent
transplantation. Similar to the effect seen after myeloablative therapy and
marrow transplantation, rGM-CSF accelerates neutrophil recovery following
cytoreductive chemotherapy in patients with nonhaematological malignancies. Less
frequent and less severe mucositis was also observed in rGM-CSF-treated versus
control patients in several studies. Importantly, adjunctive use of rGM-CSF
facilitated delivery of planned cycles of high or escalated doses of
antineoplastic drugs although the value of such chemotherapy regimens remains to
be proven. There has been no evidence to date that rGM-CSF increases the rate of
relapse of patients with haematological malignancies when administered after
myeloablative therapy and bone marrow transplantation or, in patients with acute
myelogenous leukaemia, after induction therapy. Use of rGM-CSF to recruit
quiescent leukaemic blast cells into S phase prior to chemotherapy is under
investigation. rGM-CSF has been investigated in various disorders of
haematopoiesis. A substantial number of adults and children with refractory
aplastic anaemia respond to treatment with increases in bone marrow cellularity
and peripheral blood granulocyte count; however, the response is generally not
sustained after withdrawal of rGM-CSF. Elevation of neutrophil counts may not
occur in patients with long-standing and severe aplasia; however, beneficial
stimulation of macrophage function may still occur. Generally, rGM-CSF induces
eosinophilia without correcting the neutropenia in patients with congenital
neutropenic conditions. In myelodysplasia, rGM-CSF is capable of increasing the
neutrophil count in a proportion of patients for the duration of administration.
Caution is appropriate in administering this drug to patients with high (> 14%
blasts) initial leukaemic burdens or with chronic myelomonocytic leukaemia in
view of the potential for rGM-CSF to stimulate the leukaemic clone and
precipitate acute leukaemia. Despite this concern, encouraging preliminary
results from a trial with rGM-CSF (3 ug/kg/day by subcutaneous injection) and
observation-only treatment groups suggest that, after > 6 months, the rate of
transformation to acute leukaemia is similar in both groups but that rGM-CSF
recipients have a sustained increase in neutrophil counts and an associated
reduction in infection rate. rGM-CSF 1 to 5 ug/kg/day by subcutaneous injection
ameliorates leucopenia associated with HIV infection and corrects zidovudine
(azidothymidine)-induced neutropenia without affecting the disease course as
determined by p24 antigen levels, CD4: CD8 ratios and recovery of HIV from
mononuclear cells. Similar dosages ameliorate myelosuppression induced by
ganciclovir in the treatment of AIDS-associated cytomegalovirus retinitis and by
the combination of zidovudine and interferon-alpha in treating Kaposi's sarcoma.
A trilineage response to rGM-CSF has been seen occasionally (e.g. some children
with aplastic anaemia and some patients with myelodysplasia). Disease-or drug
induced anaemia or thrombocytopenia is generally not improved; however, both
significant increases and decreases in platelet count have been reported, and the
effect of rGM-CSF on megakaryocytosis and splenic phagocyte function require
clarification. The combination of rGM-CSF with other recombinant colony
stimulating factors to expand the lineages stimulated is an exciting future
possibility. TOLERABILITY: At clinically useful dosages rGM-CSF is generally well
tolerated. Limited comparison with placebo suggests that the type and incidence
of adverse reactions reported are generally similar in both groups with the
possible exception of slightly higher incidences of diarrhoea, asthenia, rash and
malaise. However, reports from noncomparative and open-label trials indicate that
mild to moderate flu-like symptoms (myalgias, bone pain, fatigue and headache)
are common with rGM-CSF. Management of patients in whom this agent is indicated
may be complicated by rGM-CSF-induced fever and, rarely, by a capillary leak
syndrome causing fluid retention and potentially peripheral oedema, pericardial
or pleural effusions which necessitate drug withdrawal. Also reported are rash
(particularly at sites of subcutaneous injection), and occasional incidents of
central venous catheter thrombosis. The occasional report of respiratory distress
has led to the recommendation that respiratory symptoms be monitored and caution
exercised in patients with preexisting lung disease. DOSAGE AND ADMINISTRATION:
The approved (USA) dosage of yeast-derived rGM-CSF (sargramostim) for myeloid
reconstitution after autologous bone marrow transplantation is 250 ug/m2 by daily
2-hour intravenous infusions, beginning 2 to 4 hours after marrow infusion and
continued for 21 days. For management of bone marrow transplantation failure or
delayed engraftment, the approved (USA) dosage of yeast-derived rGM-CSF is 250
ug/m2/day by 2-hour intravenous infusion. Treatment should be continued for 14
days and, if clinically indicated, may be repeated after 7 days off therapy. A
third 14-day course of rGM-CSF at the increased dosage of 500 ug/m2/day by 2-hour
infusion may be administered after a further 7 days off therapy. Further dose
escalation in non-responding patients is unlikely to be of benefit. rGM-CSF has
also been successfully administered by continuous intravenous infusion and by
subcutaneous injection, including self-administration of long term therapy by the
subcutaneous route. The optimal route for administration, dose and duration of
therapy for indications other than autologous bone marrow transplantation and
failure or delay of engraftment have not been established.
PMID- 28421564
TI - Erratum to: Long-term safety and efficacy of Omnitrope(r) in adults with growth
hormone deficiency: Italian interim analysis of the PATRO Adults study.
PMID- 28421565
TI - Iron homeostasis in inflammation: a single centre prospective observational study
in medical inpatients.
AB - AIMS OF THE STUDY: We aimed to assess a potential association of iron status with
mortality and morbidity of inpatients with systemic inflammation. METHODS: This
was a single centre prospective observational study. From April 2014 to October
2014, all consecutive medical inpatients aged >=18 years with a C-reactive
protein value >5 mg/l on hospital admission were eligible for the study. We
excluded pregnant women and patients with terminal renal insufficiency or past
allogeneic stem cell transplantation. For all patients, a complete set of serum
iron parameters was obtained on hospital admission. In the final analysis, the in
hospital all-cause mortality and several morbidity measures (length of stay,
number of secondary diagnoses and Charlson Comorbidity Index) were compared
between four distinct iron status groups: patients having iron deficiency
anaemia, iron deficiency without anaemia, anaemia without iron deficiency, and
normal iron status. Iron deficiency was quantifies as the serum transferrin
receptor / ferritin index, with a cut-off level of 1.5. RESULTS: A total of 438
patients were included in the final analysis. Patients with iron deficiency had a
higher in-hospital mortality than patients with iron deficiency anaemia, anaemia
without iron deficiency, or normal iron status (6% vs 1%, 5%, and 1%,
respectively; p = 0.042). Patients with iron deficiency anaemia had a higher
number of secondary diagnoses (mean 8.4; standard deviation 4.2) and a higher
Charlson Comorbidity Index (mean 1.8; standard deviation 1.9) than patients with
iron deficiency, anaemia without iron deficiency, or normal iron status (p <0.001
and p <0.001, respectively). The median length of stay did not differ
significantly between the iron status groups (p = 0.080). CONCLUSIONS: In our
study population, iron status was significantly associated with mortality and
morbidity. Further studies are required to assess the pathophysiological and
clinical effects of an altered iron metabolism and iron substitution therapies in
inflammation.
PMID- 28421566
TI - Precision global health in the digital age.
AB - Precision global health is an approach similar to precision medicine, which
facilitates, through innovation and technology, better targeting of public health
interventions on a global scale, for the purpose of maximising their
effectiveness and relevance. Illustrative examples include: the use of remote
sensing data to fight vector-borne diseases; large databases of genomic sequences
of foodborne pathogens helping to identify origins of outbreaks; social networks
and internet search engines for tracking communicable diseases; cell phone data
in humanitarian actions; drones to deliver healthcare services in remote and
secluded areas. Open science and data sharing platforms are proposed for
fostering international research programmes under fair, ethical and respectful
conditions. Innovative education, such as massive open online courses or serious
games, can promote wider access to training in public health and improving health
literacy. The world is moving towards learning healthcare systems. Professionals
are equipped with data collection and decision support devices. They share
information, which are complemented by external sources, and analysed in real
time using machine learning techniques. They allow for the early detection of
anomalies, and eventually guide appropriate public health interventions. This
article shows how information-driven approaches, enabled by digital technologies,
can help improving global health with greater equity.
PMID- 28421567
TI - Early biomarker response and patient preferences to oral and intramuscular
vitamin B12 substitution in primary care: a randomised parallel-group trial.
AB - BACKGROUND: Vitamin B12 (VB12) deficiency can be treated with oral high-dose
substitution or intramuscular (i.m.) injection of VB12. Whenever alternative
routes of administration exist, patient preferences should be considered when
choosing the treatment. We aimed to assess outpatient preferences towards oral or
IM VB12 substitution and confirm noninferiority of early biomarker response with
oral treatment, in a typical primary care population. METHODS: Prospective
randomised nonblinded parallel-group trial. Patients were recruited by their
general practitioner and randomly assigned to oral or IM treatment. Group O-oral
was given 28 tablets of 1000 ug cyanocobalamin in a monthly punch card fitted
with an electronic monitoring system. Group I-IM received four, weekly injections
of 1000 ug hydroxocobalamin. Blood samples were drawn before the first
administration and after 1, 2 and 4 weeks of treatment, and analysed for VB12,
holotranscobalamin (HoloTc), homocysteine (Hcy) and methylmalonic acid (MMA). For
group O-oral, treatment adher-ence and percentage of days with ?2 dosing events
were calcu-lated. Before and after 28 days of treatment, patients were asked to
fill in a questionnaire about their preference for the therapy options and
associated factors. RESULTS: Between November 2013 and December 2015, 37 patients
(age: 49.5 +/- 18.5 years; women: 60.5%) were recruited for oral (19) or IM (18)
treatment. Baseline values with 95% confidence intervals for serum VB12, HoloTc,
Hcy and MMA were 158 pmol/l [145-172], 49.0 pmol/l [40.4-57.5], 14.8 umol/l [12.0
17.7] and 304 nmol/l [219-390], respective-ly, in group O-oral and 164 pmol/l
[154-174], 50.1 pmol/l [38.7-61.6], 13.0 umol/l [11.0-15.1] and 321 nmol/l [215
427], respectively, in group I-IM (not significant). After 1 month of treatment,
levels of VB12 and HoloTc showed a significant increase compared with baseline
(group O-oral: VB12 354 pmol/l [298-410] and HoloTc 156 pmol/l [116-196]; group I
IM: VB12 2796 pmol/l [1277-4314] and HoloTc 1269 pmol/l [103-2435]). Hcy and MMA
levels showed a significant decrease compared with baseline (group O-oral: Hcy
13.8 umol/l [10.7-16.8] and MMA 168 nmol/l [134-202]; group I-IM: Hcy 8.5 umol/l
[7.1-9.8] and MMA 156 nmol/l [121-190]). HoloTc and MMA levels were normalised in
all patients after 4 weeks of treatment, whereas normalisation of VB12 and Hcy
was reached by all patients in group I-IM only. Response of VB12, HoloTc and Hcy
was more pronounced in group I-IM (p <0.01) and the primary hypothesis that oral
VB12 treatment would be noninfe-rior to IM treatment was rejected. Average
adherence to thera-py was 99.6 +/- 1.1% and days with ?2 dosing events reached
5.6%. Before randomisation, preference was in favour of oral treatment (45.9%, n
= 17) over IM administration (21.6%, n = 8). Twelve patients (32.4%) had no
preference. Nine (24.3%) patients changed their preference after treatment.
Patients who obtained their preferred route of administration main-tained their
preference in the case of oral treatment and changed their preference after IM
treatment. CONCLUSIONS: Differences in VB12 levels between groups were higher
than expected. Therefore, noninferiority of oral treat-ment had to be rejected.
However, normalisation of HoloTc and MMA was reached by all patients after a 1
month treatment period. The clinical benefit of the exaggerated biomarker re
sponse after IM treatment within a typical primary care popula-tion is
questionable. Midterm biomarker effects and patient preferences should be
considered when a therapeutic scheme is chosen. Initial rating in favour of
either IM or oral therapy can change over time and justifies repeated re
evaluation of patient preferences. (ClinicalTrials.gov ID NCT01832129).
PMID- 28421568
TI - Prions, prionoid complexes and amyloids: the bad, the good and something in
between.
AB - Prions are infectious agents causing transmissible spongiform encephalopathies in
humans and animals. These protein-based particles template conformational changes
in a host-encoded prion protein to an insoluble self-like conformation. Prions
are also present in yeast, where they support protein-based epigenetic
inheritance. There is emerging evidence that prion-like (prionoid) particles can
support a variety of pathological and beneficial functions. The recent data on
the prionoid spread of other pathological amyloids are discussed in light of
differences between prions and prion-like aggregates. On the other hand, prion
like action has also been found to support important functions such as memory,
and amyloids were shown to have a variety of physiological roles from storage to
scaffolding in simple organisms and in humans. Higher-order protein complexes
play important roles in signalling. Many death-fold domains can polymerise upon
nucleation to enhance sensitivity and induce a robust response. Although these
polymers are structurally different from amyloids, some of them are characterised
by prionoid activities, such as intercellular spread. The initial activation of
these complexes is vital for organismal health, whereas prolonged activation
leading to unresolved inflammation underlies autoinflammatory and other diseases.
Prionoid complexes play important roles far beyond prion diseases and
neurodegeneration.
PMID- 28421569
TI - Two-step procedure for complicated appendicitis with perityphlitic abscess
formation.
AB - PRINCIPLES: Optimal management of perforated appendicitis with perityphlitic
phlegmon or abscess formation is controversial. The aim of the study was to
assess the outcome after a two-step procedure to treat patients with
perityphlitic abscess formation. METHODS: We retrospectively assessed
prospectively collected data from a single-centre database that included adult
patients who had appendicitis and perityphlitic abscess (>=3 cm) but no
generalised peritonitis, and were treated in 2007-2015. Patients underwent a two
step procedure that comprised antibiotic treatment and drainage when technically
feasible (step 1) followed by interval appendectomy (step 2). We evaluated
treatment modalities, complications and outcomes. RESULTS: Out of a total of 1480
patients with appendicitis, 15 patients presented with perityphlitic abscess. In
addition to antibiotic treatment, computed tomography-guided drainage was
performed in 12 of these cases. Step 1 and 2 hospital stays were (median, range)
7 days (5-14 days) and 2 days (2-12 days), respectively. One patient's abscess
recurred after 2 months, associated with new onset appendicitis and perforation.
Another patient underwent reoperation after interval appendectomy for suspected
postoperative peritonitis. CONCLUSION: This two-step procedure for appendicitis
with appendicular abscess was highly successful (100%) with a low rate of
complications (13%). In the view of a potentially increased rate of appendicular
neoplasm in combination with abscess formation, the role of interval appendectomy
has to be evaluated in larger trials.
PMID- 28421570
TI - "Real world" experience in Cardiac Resynchronization Therapy at a Swiss Tertiary
Care Center.
AB - BACKGROUND: Based on a reduction in morbidity and mortality, cardiac
resynchronisation therapy (CRT) has evolved as a standard therapy for patients
with advanced heart failure. OBJECTIVE: To provide insight into patient
demographics, safety, echocardiographic remodelling and long-term follow-up of
patients treated with CRT in a "real-world" setting at a Swiss tertiary care
centre. METHODS: Patients implanted with a CRT device at the University Heart
Centre Zurich between 2000 and 2015 were consecutively enrolled. Initial clinical
and echocardiographic therapy response as well as long-term follow-up for
mortality (defined as all-cause death, heart transplantation or ventricular
assist device implantation) and hospitalisation for heart failure were assessed.
RESULTS: A total of 418 patients with a median age of 66 years at the time of CRT
implantation (78% male) were enrolled. Serious peri-interventional complications
(from the time of implantation up to 14 days thereafter) were rare and included
systemic infections in 2.4%, pneumothorax in 3.3% and haematoma requiring
revision in 2.2% of cases. Overall, the Kaplan-Meier estimate for 5-year freedom
from the composite endpoint (hospitalisation for heart failure or mortality) was
55.8%; the Kaplan-Meier estimate for 5-year freedom from mortality was 64.1%. CRT
was associated with a significant symptomatic improvement and left ventricular
reverse remodelling. Overall, 3.9% of patients did not respond to cardiac
resynchronisation therapy (decline in left ventricular ejection fraction [LVEF]
>5%), whereas 35.1% experienced neither a continued decline nor a relevant
improvement of LVEF (+/-5%). In the remaining 61% of patients we observed an
improvement in LVEF of more than 5%. Forty percent and 31% of patients were super
responders, defined as an absolute LVEF improvement of ?10% and by a relative
reduction of left ventricular end-diastolic volume index by 20% or more. Super
response to CRT was associated with a significant benefit in terms of survival
and rehospitalisation rates. CONCLUSION: Our data are consistent with large
multicentre trials and indicate that CRT is similarly effective in a real-world
setting in Switzerland.
PMID- 28421571
TI - [Lessons from historic psychiatric records regarding the effects of
antipsychotics?]
PMID- 28421572
TI - [Suicidal behaviour among prisoners: prevalence and association with
psychological distress in Flemish prisons].
AB - BACKGROUND: Internationally, the prevalence of suicidal behaviour (suicidal
ideation, suicide plan and attempted suicide) is significantly elevated among
prisoners compared to the community at large. AIM: To estimate the prevalence of
suicidal behaviour among prisoners in the Flanders region of Belgium, to identify
differences according to gender and custodial status, and to examine the
association of recent suicidal ideation and suicide plan with psychological
distress. METHOD: We performed a cross-sectional survey using a representative
sample of 1,326 prisoners, randomly selected from 15 Flemish prisons. RESULTS:
During their lifetime, an estimated 44.4% of prisoners in Flanders reported
suicidal ideation, 30.2% made a suicide plan, and one-fifth (21.8%) attempted
suicide at least once. Past-year suicidal ideation in prison was endorsed by one
fourth (24.9%) of all prisoners, and 14.3% made a recent suicidal plan during
their current incarceration. Approximately one in ten prisoners (9.5%) attempted
suicide while in prison. Recent suicidal ideation and suicide plan were
significantly associated with high levels of psychological distress. Generally,
female prisoners reported significant higher levels of suicidal behaviour than
men, while differences according to custodial status were less unequivocal.
CONCLUSION: Corroborating international research findings, high rates of suicidal
behaviour were identified among prisoners in Flanders, compared to the general
population. Not only is suicidal behaviour a significant risk factor for suicide,
it is also important in its own right as an indicator of profound psychological
distress. Suicidal behaviour should therefore be an important target for
prevention and intervention in this at-risk population.
PMID- 28421573
TI - [Forensic (flexible) assertive community treatment: client characteristics and
treatment outcomes].
AB - BACKGROUND: (Flexible) Assertive community treatment ((f)act) is applied
increasingly to forensic psychiatric clients. However, evidence about the
effectiveness of forensic (f)act is scanty. AIM: To investigate to what extent
(subgroups of) clients receiving care from forensic (f)act teams show, after a
year, changes in their social and psychological functioning and are subjected to
fewer justicial outcome measures. METHOD: Between 2009 and 2011, eight forensic
(f)act teams collected, at two measurement moments separated by an average of 12
months, data relating to client characteristics and outcomes of care. The study
involved 202 clients. RESULTS: After a year clients showed significant
improvements in psychological and social functioning, and had fewer
confrontations with the police and the law. They were detained less often and for
shorter periods and were considered to be less likely to reoffend. The number of
admissions to mental health care and to addiction and forensic care remained
constant. CONCLUSION: Clients with a psychiatric disorder and likely to display
criminal behaviour showed improvement while being treated by forensic (f)act
teams. Further research is needed to prove whether forensic (f)act treatment will
have the desired effects in the longer term and will enjoy the status of being
regarded as evidence based practice.
PMID- 28421574
TI - [Compulsory treatment in the community for persons in need of mental health
care].
AB - BACKGROUND: Clinical admissions and inpatient services are increasingly replaced
by enhanced community treatment in Western countries. Currently the Dutch mental
health legislation is being revised, making compulsory community treatment a
novel legal option in The Netherlands. AIM: To summarize the current literature
on compulsory community treatment and to review studies relating to efficacy,
patients' and carers' perspectives, and costs. METHOD: We conducted a systematic
review of the literature, using PubMed and Trip. RESULTS: Current literature does
not provide evidence for positive effects of cct in comparison to voluntary care
in terms of admission duration, time-to-readmission, and clinical outcomes.
CONCLUSION: Results from England and the United States do not provide support for
efficacy of cct in terms of number and/or duration of hospital admissions, and in
terms of clinical outcomes compared to voluntary treatment. There is a pressing
need for studies designed to allow for direct comparisons between outcomes after
compulsory hospital admission and compulsory community treatment.
PMID- 28421575
TI - [Prescribing psychotropic medication by the nurse practitioner in mental health
care: an explorative study].
AB - BACKGROUND: Since January 1, 2012, nurse practitioners (NP) working in mental
health care are allowed to prescribe psychotropic medication. So far, there has
been very little research on the results of this decision that now let NPS share
with doctors prescribing psychotropic drugs. AIM: To provide insight into how
patients and psychiatrists experience the prescribing behaviours of NPS and how
NPS themselves regard their extended role. METHOD: We performed an explorative
study in which we used the data given in prescriptions written by NPS,
questionnaires exploring patients' experiences and semi-structured interviews
with psychiatrists and NPS. RESULTS: Between May 2014 and May 2015, 13 NPS wrote
3542 prescriptions for 565 unique patients. On the whole, patients, psychiatrists
and NPS expressed positive views on the prescribing of psychotropic medication by
NPS. CONCLUSION: Our research project confirms that the various stakeholders are
satisfied with the prescribing practices of NPS. A follow-up study is needed in
order to ascertain whether there are qualitative differences between the
prescriptions of NPS and those of doctors.
PMID- 28421576
TI - [Confusion caused by dietary supplement lithium orotate].
AB - A 38-year-old woman was referred to our hospital with pelvic inflammatory
disease. She had been diagnosed as having a tubo-ovarian abscess, for which
antibiotic therapy with metronidazole and levofloxacin was indicated. Because the
patient was already taking lithium she was prescribed clindamycin instead of
metronidazole, a drug that interacts with lithium. For the same reason, naproxen
could not be prescribed to reduce pain. However, the lithium taken by the patient
turned out to be a dietary supplement containing lithium orotate which she had
obtained via the Internet. Because the serum lithium level proved to be below
0.05 mmol/l clindamycin was still replaced by metronidazole, and naproxen could
be started.
PMID- 28421577
TI - ?
PMID- 28421578
TI - ?
PMID- 28421579
TI - ?
PMID- 28421580
TI - ?
PMID- 28421581
TI - [Are you for or against ROM?]
PMID- 28421582
TI - Polish Forum for Prevention Guidelines on Smoking: update 2017.
PMID- 28421583
TI - Heater-cooler unit contamination with Mycobacterium chimaera - potential harmful
risks for cardiac surgery patients.
PMID- 28421584
TI - Left main coronary artery quadrifurcation and acute coronary syndrome.
PMID- 28421585
TI - Left ventricular non-compaction associated with hypertrophic cardiomyopathy in
the same patient.
PMID- 28421586
TI - Cardiac approach to a patient with breast cancer and metastases in
musculoskeletal system.
PMID- 28421587
TI - Intensive exercise and its effect on the heart: Is more always better?
PMID- 28421588
TI - Takotsubo syndrome after pericardial tamponade following cryoballoon ablation of
pulmonary veins for paroxysmal atrial fibrillation and complicated by right
coronary artery thrombosis.
PMID- 28421589
TI - Spontaneous coronary dissection: Optical coherence tomography insights before and
after stenting.
PMID- 28421590
TI - Double outlet right ventricle with absent infundibular septum and common
ventriculo-arterial valve.
PMID- 28421591
TI - "Full Plastic-Jacket": Reconstruction of 18 cm of coronary arteries with
bioresorbable vascular scaffolds in a young patient with ST-elevation myocardial
infarction and multivessel disease.
PMID- 28421592
TI - Left ventricular improvement due to allogeneic CB-MNCs transplantation in a
chronic heart failure six-years after myocardial infarction.
PMID- 28421593
TI - Determinants of improvement in six-minute walk distance from admission to
discharge in acute systolic heart failure: Analysis from the ESCAPE trial.
PMID- 28421594
TI - Anti-aggregation therapy in patients with acute coronary syndrome -
recommendations for medical emergency teams. Experts' standpoint.
PMID- 28421595
TI - Acute occlusion of the superficial femoral artery in a very young woman.
PMID- 28421596
TI - The relation between skin conductance responses and recovery from symptoms of
PTSD.
AB - BACKGROUND: The purpose was to investigate if potentially stressful reminders of
the intensive care unit (ICU) stay influenced variability in transient skin
conductance responses, and whether such changes were associated with post
traumatic stress symptoms (PTSS), and development of symptoms over time. METHODS:
Thirty patients with an ICU length of stay > 48 h were included in the study.
Within the week after ICU discharge (T1), patients were exposed to authentic ICU
sound and questions regarding traumatic ICU memories while skin conductance
reactivity was monitored. PTSS was assessed using PTSS-10 at T1 and again 3
months later (T2). Changes in number of skin conductance fluctuations per second
(NSCF) between baseline and during the cueing conditions and in relation to PTSS
scores (T1) were investigated. PTSS scores at T2 and changes between T1 and T2
(PTSS-CS) were used to investigate if reactivity in NSCF could predict symptoms
of PTSD. RESULTS: The results showed increases in NSCF during both situational
and verbal cueing, compared to baseline. However, no relation to PTSS scores was
indicated. Negative correlations between NSCF during situational cueing and both
PTSS-T2 and PTSS-CS were found among women, but not among men. CONCLUSION: A low
variability, or reactivity in skin conductance responses to situational cues
could imply a risk of developing, or not being able to recover from, symptoms of
PTSD in women. As such, the measurement could be used to predict this risk in
women. However, further studies are necessary to evaluate this area of
application.
PMID- 28421597
TI - Analysis of an electrical impedance spectroscopy system in short-term digital
dermoscopy imaging of melanocytic lesions.
AB - BACKGROUND: Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic
technique that measures tissue impedance. OBJECTIVES: To evaluate the effect of
adding an EIS measurement at baseline to suspicious melanocytic lesions
undergoing routine short-term sequential digital dermoscopy imaging (SDDI).
METHODS: Patients presented with suspicious melanocytic lesions that were
eligible for short-term SDDI (with no clear feature of melanoma on dermoscopy).
EIS measurement was performed at the first visit following dermoscopic
photography. Normally, an EIS score of >= 4 is considered positive; however, this
protocol investigated a higher cut-off in combination with SDDI. When the EIS
score was >= 7 the lesion was excised immediately owing to the high risk of
melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3
month period. RESULTS: From a total of 160 lesions analysed, 128 of 154 benign
lesions received an EIS score of 0-6, giving a specificity of the EIS method for
the diagnosis of melanoma of 83.1% [95% confidence interval (CI) 76.3-88.7]. Five
of the six melanomas found in this study had an EIS score >= 7, with a
sensitivity for melanoma diagnosis of 83.3% (95% CI 35.9-99.6). When EIS 0-6
lesions were subsequently followed up with SDDI, one additional melanoma was
detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of
100% (95% CI 54.1-100; six of six malignant melanomas excised) and a specificity
of 69.5% (95% CI 61.5-76.6; 107 of 154 benign lesions not excised). CONCLUSIONS:
If utilizing a protocol where an EIS score <= 3 requires no SDDI and >= 7
requires immediate excision, it reduced the need for SDDI by 46.9% (n = 75/160;
95% CI 39.0-54.9).
PMID- 28421598
TI - Fluorescence-advanced videodermatoscopy: a new method for in vivo skin
evaluation.
PMID- 28421599
TI - Surgery versus conservative management of endometriomas in subfertile women. A
systematic review.
AB - INTRODUCTION: Endometriomas are present in up to 44% of all women with
endometriosis and have a detrimental effect on fertility. However, it is
controversial whether endometriomas should be surgically removed before assisted
reproduction technology. Our purpose was to evaluate whether surgical stripping
of endometriomas in subfertile women improves the chance of a live birth.
Secondary outcomes were impact on ovarian reserve and pain. MATERIAL AND METHODS:
We conducted a systematic review and meta-analysis with results reported in
accordance to the PRISMA guidelines. A summary of findings table was developed
using GRADE. We searched Medline and Embase. Two reviewers performed the
screening. RESULTS: Of 686 manuscripts, we included one randomized controlled
trial and nine retrospective cohort studies, mostly of low quality. The odds
ratio for live birth after surgery [compared with conservative management before
in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)] was 0.87
(95% CI 0.64-1.18, six studies, I2 = 3%; ????, VERY LOW quality). The mean
difference of antral follicle count was -2.09 (95% CI -4.84 to 0.67, four
studies). No difference was observed regarding antral follicle count between the
two groups (MD -2.09, 95% CI -4.84 to 0.67, four studies, ????, VERY LOW
quality). Pain outcome was not reported in the included studies. CONCLUSION: The
very low quality evidence suggests no difference in odds ratio of live birth
between women who underwent surgery for endometriomas before IVF/ICSI compared
with conservative management. Further high quality studies are needed, but due to
a lack of convincing evidence favoring surgery, we recommend considering
conservative treatment if the only indication is subfertility.
PMID- 28421600
TI - Lay-led and peer support interventions for adolescents with asthma.
AB - BACKGROUND: Adolescents with asthma are at high risk of poor adherence with
treatment. This may be compounded by activities that worsen asthma, in particular
smoking. Additional support above and beyond routine care has the potential to
encourage good self-management. We wanted to find out whether sessions led by
their peers or by lay leaders help to reduce these risks and improve asthma
outcomes among adolescents. OBJECTIVES: To assess the safety and efficacy of lay
led and peer support interventions for adolescents with asthma. SEARCH METHODS:
We identified trials from the Cochrane Airways Trials Register, which contains
reports of randomised trials obtained from multiple electronic and handsearched
sources, and we searched trial registries and reference lists of primary studies.
We conducted the most recent searches on 25 November 2016. SELECTION CRITERIA:
Eligible studies randomised adolescents with asthma to an intervention led by lay
people or peers or to a control. We included parallel randomised controlled
trials with individual or cluster designs. We included studies reported as full
text, those published as abstract only and unpublished data. DATA COLLECTION AND
ANALYSIS: Two review authors screened the searches, extracted numerical data and
study characteristics and assessed each included study for risk of bias. Primary
outcomes were asthma-related quality of life and exacerbations requiring at least
a course of oral steroids. We graded the analyses and presented evidence in a
'Summary of findings' table.We analysed dichotomous data as odds ratios, and
continuous data as mean differences (MD) or standardised mean differences, all
with a random-effects model. We assessed clinical, methodological and statistical
heterogeneity when performing meta-analyses, and we described skewed data
narratively. MAIN RESULTS: Five studies including a total of 1146 participants
met the inclusion criteria for this review. As ever with systematic reviews of
complex interventions, studies varied by design (cluster and individually
randomised), duration (2.5 to 9 months), setting (school, day camp, primary care)
and intervention content. Most risk of bias concerns were related to blinding and
incomplete reporting, which limited the meta-analyses that could be performed.
Studies generally controlled well for selection and attrition biases.All
participants were between 11 and 17 years of age. Asthma diagnosis and severity
varied, as did smoking prevalence. Three studies used the Triple A programme; one
of these studies tested the addition of a smoke-free pledge; another delivered
peer support group sessions and mp3 messaging to encourage adherence; and the
third compared a peer-led asthma day camp with an equivalent camp led by
healthcare practitioners.We had low confidence in all findings owing to risk of
bias, inconsistency and imprecision. Results from an analysis of asthma-related
quality of life based on the prespecified random-effects model were imprecise and
showed no differences (MD 0.40, 95% confidence interval (CI) -0.02 to 0.81); a
sensitivity analysis based on a fixed-effect model and a responder analysis
suggested small benefit may be derived for this outcome. Most other results were
summarised narratively and did not show an important benefit of the intervention;
studies provided no analysable data on asthma exacerbations or unscheduled visits
(data were skewed), and one study measuring adherence reported a drop in both
groups. Effects on asthma control favoured the intervention but findings were not
statistically significant. Results from two studies with high levels of baseline
smoking showed some promise for self-efficacy to stop smoking, but overall
nicotine dependence and smoking-related knowledge were not significantly better
in the intervention group. Investigators did not report adverse events. AUTHORS'
CONCLUSIONS: Although weak evidence suggests that lay-led and peer support
interventions could lead to a small improvement in asthma-related quality of life
for adolescents, benefits for asthma control, exacerbations and medication
adherence remain unproven. Current evidence is insufficient to reveal whether
routine use of lay-led or peer support programmes is beneficial for adolescents
receiving asthma care.Ongoing and future research may help to identify target
populations for lay-led and peer support interventions, along with attributes
that constitute a successful programme.
PMID- 28421602
TI - The qualitative f-ratio method applied to electron channelling-induced x-ray
imaging with an annular silicon drift detector in a scanning electron microscope
in the transmission mode.
AB - Electron channelling is known to affect the x-ray production when an accelerated
electron beam is applied to a crystalline material and is highly dependent on the
local crystal orientation. This effect, unless very long counting time are used,
is barely noticeable on x-ray energy spectra recorded with conventional silicon
drift detectors (SDD) located at a small elevation angle. However, the very high
count rates provided by the new commercially available annular SDDs permit now to
observe this effect routinely and may, in some circumstances, hide the true
elemental x-ray variations due to the local true specimen composition. To
circumvent this issue, the recently developed f-ratio method was applied to
display qualitatively the true net intensity x-ray variations in a thin specimen
of a Ti-6Al-4V alloy in a scanning electron microscope in transmission mode. The
diffraction contrast observed in the x-ray images was successfully cancelled
through the use of f-ratios and the true composition variations at the grain
boundaries could be observed in relation to the dislocation alignment prior to
the beta-phase nucleation. The qualitative effectiveness in removing channelling
effects demonstrated in this work makes the f-ratio, in its quantitative form, a
possible alternative to the ZAF method in channelling conditions.
PMID- 28421601
TI - Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and
Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile
dermatomyositis among paediatric dermatologists, rheumatologists and
neurologists.
AB - BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be
reliable and valid outcome measures to assess cutaneous disease in adult
dermatomyositis (DM) and juvenile DM (JDM), respectively. OBJECTIVES: This study
compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric
rheumatologists and paediatric neurologists in patients with JDM. METHODS: Five
paediatric dermatologists, five paediatric rheumatologists and five paediatric
neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and
skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra
rater reliability, construct validity and completion time were compared. RESULTS:
Inter-rater reliability for CDASI activity and damage scores was good to moderate
for paediatric dermatologists and rheumatologists, but poor for paediatric
neurologists. The inter-rater reliability for CAT-BM activity scores was moderate
for paediatric dermatologists and rheumatologists, but poor for paediatric
neurologists and poor across all specialties for damage scores. Intra-rater
reliability for the CDASI and CAT-BM activity and damage scores was moderate to
excellent for paediatric dermatologists, rheumatologists and neurologists. Strong
associations were found between skin PGA activity and damage scores and CDASI or
CAT-BM activity and damage scores, respectively (P < 0.002). The CDASI had a mean
completion time of 5.4 min compared with that for the CAT-BM of 3.1 min.
CONCLUSIONS: Our data confirm the reliability of the CDASI activity and damage
scores and the CAT-BM activity scores when used by paediatric dermatologists and
rheumatologists in assessing JDM. Significant variation existed in the paediatric
neurologists' scores.
PMID- 28421603
TI - High payload itraconazole-incorporated lipid nanoparticles with modulated release
property for oral and parenteral administration.
AB - OBJECTIVES: The aim of this study was to develop high payload itraconazole
incorporated lipid nanoparticles (HINP) with modulated release property using a
binary mixture core of solid and liquid lipid for oral and parenteral
administration. METHODS: High payload itraconazole-incorporated lipid
nanoparticles were prepared by hot high-pressure homogenization method using
tristearin (TS) as a solid lipid, triolein (TO) as a liquid lipid and egg
phosphatidylcholine/Tween 80/DSPE-PEG2000 as a surfactants mixture. To
investigate the effects of liquid lipid in lipid core on itraconazole (ITZ)
dissolution and release, TS/TO ratio was varied as 100/0, 90/10 and 80/20
(mg/mg). KEY FINDINGS: All HINP formulations showed particle size around 300 nm
and polydispersity index below 0.3. The incorporation efficiencies of HINP
formulations were above 80%, and more than 40 mg of ITZ was incorporated into
each HINP formulation. In-vitro dissolution and release rate of ITZ from HINP
increased as the amount of TO in lipid core increased. Compared with commercial
formulations of ITZ, the pharmacokinetics of ITZ was improved after oral and
parenteral administration of HINP formulations containing 0% or 10% of TO in
lipid core. CONCLUSION: High payload itraconazole-incorporated lipid
nanoparticles with a binary mixture lipid core have a great potential for the
development of controlled release formulation of ITZ.
PMID- 28421604
TI - Comparison of adverse pregnancy outcomes based on the new IADPSG 2010 gestational
diabetes criteria and maternal body mass index.
AB - BACKGROUND: The diagnostic criteria for gestational diabetes (GDM) have been
controversial following the International Association for Pregnancy Study Groups
(IADPSG) 2010 recommendations to lower the diagnostic fasting blood sugar level
threshold. AIM: To assess the pregnancy-related outcomes of women according to
the different diagnostic criteria for GDM adjusting for body mass index
categories. METHOD: A retrospective observational cohort study was conducted on
4081 pregnant women with positive 50 g glucose challenge test but without pre
gestational diabetes. Participants were grouped into four cohorts: no GDM
(control group); GDM on Australasian Diabetes in Pregnancy (ADIPS) 1998 criteria
only (treated); GDM on IADPSG 2010 criteria only (untreated); and GDM on both
criteria (treated). The association of each cohort with pregnancy outcome
measures, including birthweight centile, delivery gestation, primary caesarean
section, shoulder dystocia and stillbirth, together with the effect of obesity,
were examined. RESULTS: Women diagnosed with GDM according to the IADPSG 2010
(untreated) but not the ADIPS 1998 criteria (treated) had an increased risk of
being large for gestational age (LGA) (odds ratio (OR) = 2.45, 95% CI: 1.46-4.12,
P = 0.001) and primary caesarean section (OR = 2.03, 95% CI: 1.23-3.35, P =
0.006) compared to control women. Among the women in this untreated group and
women without GDM, obese women had an increased risk of LGA (OR = 3.82, 95% CI:
2.87-5.10, P < 0.001), shoulder dystocia (OR = 1.50, 95% CI: 1.03-2.19, P = 0.04)
and primary caesarean section (OR = 1.63, 95% CI: 1.26-2.10, P < 0.001), compared
to those women of normal weight. These associations remained significant on
multivariate analysis. CONCLUSION: Untreated women who would be diagnosed with
GDM using the new criteria have an increased risk of pregnancy complications,
with maternal obesity having an even greater risk.
PMID- 28421605
TI - Cholinergic/glutamatergic co-transmission in striatal cholinergic interneurons:
new mechanisms regulating striatal computation.
AB - It is well established that neurons secrete neuropeptides and ATP with classical
neurotransmitters; however, certain neuronal populations are also capable of
releasing two classical neurotransmitters by a process named co-transmission.
Although there has been progress in our understanding of the molecular mechanism
underlying co-transmission, the individual regulation of neurotransmitter
secretion and the functional significance of this neuronal 'bilingualism' is
still unknown. Striatal cholinergic interneurons (CINs) have been shown to
secrete glutamate (Glu) in addition to acetylcholine (ACh) and are recognized for
their role in the regulation of striatal circuits and behavior. Our review
highlights the recent research into identifying mechanisms that regulate the
secretion and function of Glu and ACh released by CINs and the roles these
neurons play in regulating dopamine secretion and striatal activity. In
particular, we focus on how the transporters for ACh (VAChT) and Glu (VGLUT3)
influence the storage of neurotransmitters in CINs. We further discuss how these
individual neurotransmitters regulate striatal computation and distinct aspects
of behavior that are regulated by the striatum. We suggest that understanding the
distinct and complementary functional roles of these two neurotransmitters may
prove beneficial in the development of therapies for Parkinson's disease and
addiction. Overall, understanding how Glu and ACh secreted by CINs impacts
striatal activity may provide insight into how different populations of
'bilingual' neurons are able to develop sophisticated regulation of their targets
by interacting with multiple receptors but also by regulating each other's
vesicular storage. This is an article for the special issue XVth International
Symposium on Cholinergic Mechanisms.
PMID- 28421607
TI - Laterality and grip strength influence hand bone micro-architecture in modern
humans, an HRpQCT study.
AB - It is widely hypothesized that mechanical loading, specifically repetitive low
intensity tasks, influences the inner structure of cancellous bone. As such,
there is likely a relationship between handedness and bone morphology. The aim of
this study is to determine patterns in trabecular bone between dominant and non
dominant hands in modern humans. Seventeen healthy patients between 22 and 32
years old were included in the study. Radial carpal bones (lunate, capitate,
scaphoid, trapezium, trapezoid, 1st, 2nd and 3rd metacarpals) were analyzed with
high-resolution micro-computed tomography. Additionally, crush and pinch grip
were recorded. Factorial analysis indicated that bone volume ratio, trabeculae
number (Tb.N), bone surface to volume ratio (BS.BV), body weight, stature and
crush grip were all positively correlated with principal components 1 and 2
explaining 78.7% of the variance. Volumetric and trabecular endostructural
parameters (BV/TV, BS/BV or Tb.Th, Tb.N) explain the observed inter-individual
variability better than anthropometric or clinical parameters. Factors analysis
regressions showed correlations between these parameters and the dominant side
for crush strength for the lunate (r2 = 0.640, P < 0.0001), trapezium (r2 =
0.836, P < 0.0001) and third metacarpal (r2 = 0.763). However, despite a
significant lateralization in grip strength for all patients, the endostructural
variability between dominant and non-dominant sides was limited in perspective to
inter-individual differences. In conclusion, handedness is unlikely to generate
trabecular patterns of asymmetry. It appears, however, that crush strength can be
considered for endostructural analysis in the modern human wrist.
PMID- 28421606
TI - Role of mucosa in generating spontaneous activity in the guinea pig seminal
vesicle.
AB - KEY POINTS: The mucosa may have neuron-like functions as urinary bladder mucosa
releases bioactive substances that modulate sensory nerve activity as well as
detrusor muscle contractility. However, such mucosal function in other visceral
organs remains to be established. The role of mucosa in generating spontaneous
contractions in seminal vesicles (SVs), a paired organ in the male reproductive
tract, was investigated. The intact mucosa is essential for the generation of
spontaneous phasic contractions of SV smooth muscle arising from electrical slow
waves and corresponding increases in intracellular Ca2+ . These spontaneous
events primarily depend on Ca2+ handling by sarco-endoplasmic reticulum Ca2+
stores. A population of mucosal cells developed spontaneous rises in
intracellular Ca2+ relying on sarco-endoplasmic reticulum Ca2+ handling. The
spontaneously active cells in the SV mucosa appear to drive spontaneous activity
in smooth muscle either by sending depolarizing signals and/or by releasing
humoral substances. ABSTRACT: The role of the mucosa in generating the
spontaneous activity of guinea-pig seminal vesicle (SV) was explored. Changes in
contractility, membrane potential and intracellular Ca2+ dynamics of SV smooth
muscle cells (SMCs) were recorded using isometric tension recording,
intracellular microelectrode recording and epi-fluorescence Ca2+ imaging,
respectively. Mucosa-intact but not mucosa-denuded SV preparations generated TTX-
(1 MUm) resistant spontaneous phasic contractions that were abolished by
nifedipine (3 MUm). Consistently, SMCs developed mucosa-dependent slow waves
(SWs) that triggered action potentials and corresponding Ca2+ flashes. Nifedipine
(10 MUm) abolished the action potentials and spontaneous contractions, while
suppressing the SWs and Ca2+ flashes. Both the residual SWs and spontaneous Ca2+
transients were abolished by cyclopiazonic acid (CPA, 10 MUm), a sarco
endoplasmic reticulum Ca2+ -ATPase (SERCA) inhibitor. DIDS (300 MUm) and niflumic
acid (100 MUm), blockers for Ca2+ -activated Cl- channels (CACCs), or low Cl-
solution also slowed or prevented the generation of SWs. In SV mucosal
preparations detached from the muscle layer, a population of mucosal cells
generated spontaneous Ca2+ transients that were blocked by CPA but not
nifedipine. These results suggested that spontaneous contractions and
corresponding Ca2+ flashes in SV SMCs arise from action potential generation due
to the opening of L-type voltage-dependent Ca2+ channels. Spontaneous Ca2+
transients appear to primarily result from Ca2+ release from sarco-endoplasmic
reticulum Ca2+ stores to activate CACCs to develop SWs. The mucosal cells firing
spontaneous Ca2+ transients may play a critical role in driving spontaneous
activity of SV smooth muscle either by sending depolarizing signals or by
releasing humoral substances.
PMID- 28421608
TI - Can functional emotion regulation protect children's mental health from war
trauma? A Palestinian study.
AB - Effective emotion regulation (ER) is expected to protect mental health in
traumatic stress. We first analysed the protective (moderator) function of
different ER strategies and the associations between ER and mental health.
Second, we tested gender differences in the protective function of ER and the
associations between ER strategies and mental health. Participants were 482
Palestinian children (girls 49.4%; 10-13 years, M = 11.29, SD = .68) whose ER was
assessed by the Emotion Regulation Questionnaire and mental health by post
traumatic stress (Children's Impact Event Scale), depressive, and psychological
distress (Strengths and Difficulties Questionnaire) symptoms, and by psychosocial
well-being (Mental Health Continuum-Short Form). War trauma involved 42 events.
Results showed, first, that none of the ER strategies could protect a child's
mental health from negative impact of war trauma, but self-focused ER was
associated with low depressive symptoms, and other-facilitated ER with high
psychological well-being. However, controlling of emotions formed a comprehensive
risk for children's mental health. Second, gender differences were found in the
protective role of ER, as self-focused and distractive ER formed a vulnerability
among boys. The results are discussed in the context of emotional and regulative
demands of war and life-threat.
PMID- 28421609
TI - Description and quantitative analysis of the dentition of the southern thorny
skate Amblyraja doellojuradoi.
AB - A description of the tooth morphology of 234 jaws from the southern thorny skate
Amblyraja doellojuradoi in the south-west Atlantic Ocean is given. Seven rows of
teeth were selected and length and width of each tooth in these rows were
measured. It was found that functional series corresponds to the third teeth and
the average width and length of these teeth were compared among jaws, maturity
stages, sexes and rows. Generalized linear models were used to determine the
subset of measures that most contribute to explain the variability between
groups. It was observed that males have longer teeth than females, but the teeth
of females are wider. These differences are attributed to reproductive behaviour,
in which males bite females to hold them during copulation. This study provides a
description of the teeth of A. doellojuradoi, supplying a valuable tool for
identification of species. In addition, the establishment of the main variations
observed in the dentition, improves the understanding of the species' biology.
PMID- 28421610
TI - Use of vegetable oils in dermatology: an overview.
AB - Vegetable oils have been used for a wide variety of purposes since time
immemorial; however, their principle use remains as skin moisturizers, especially
in neonates and children. Because of their considerable efficacy and a low side
effect profile and bearable cost, these oils are hugely popular as moisturizers
among the common people in countries such as India. A wide variety of oils have
been used, and newer ones are coming up with each passing day. This article
focuses on the different types of vegetable oils and their varied uses in
dermatology.
PMID- 28421611
TI - Breast-density measurement using photon-counting spectral mammography.
AB - PURPOSE: To evaluate a method for measuring breast density using photon-counting
spectral mammography. Breast density is an indicator of breast cancer risk and
diagnostic accuracy in mammography, and can be used as input to personalized
screening, treatment monitoring and dose estimation. METHODS: The measurement
method employs the spectral difference in x-ray attenuation between adipose and
fibro-glandular tissue, and does not rely on any a priori information. The method
was evaluated using phantom measurements on tissue-equivalent material (slabs and
breast-shaped phantoms) and using clinical data from a screening population
(n=1329). A state-of-the-art nonspectral method for breast-density assessment was
used for benchmarking. RESULTS: The precision of the spectral method was
estimated to be 1.5-1.8 percentage points (pp) breast density. Expected
correlations were observed in the screening population for thickness versus
breast density, dense volume, breast volume, and compression height. Densities
ranged between 4.5% and 99.6%, and exhibited a skewed distribution with a mode of
12.5%, a median of 18.3%, and a mean of 23.7%. The precision of the nonspectral
method was estimated to be 2.7-2.8 pp. The major uncertainty of the nonspectral
method originated from the thickness estimate, and in particular thin/dense
breasts posed problems compared to the spectral method. CONCLUSIONS: The spectral
method yielded reasonable results in a screening population with a precision
approximately two times that of the nonspectral method, which may improve or
enable applications of breast-density measurement on an individual basis such as
treatment monitoring and personalized screening.
PMID- 28421612
TI - Prospective bacterial quorum sensing inhibitors from Indian medicinal plant
extracts.
AB - : As virulence of many pathogenic bacteria is regulated by the phenomenon of
quorum sensing (QS), the present study aimed to find the QS-inhibiting (QS-I)
property (if any) in 61 Indian medicinal plants. The presence of QS-I compound in
the leaf extract was evaluated by its ability to inhibit production of pigment in
Chromobacterium violaceum MTCC 2656 (violacein) and Pseudomonas aeruginosa MTCC
2297 (pyocyanin) or swarming of P. aeruginosa MTCC 2297. Extracts of three
plants, Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis, have shown
a dose-dependent inhibition of violacein production with no negative effect on
bacterial growth. Inhibition of pyocyanin pigment production and swarming
motility in P. aeruginosa MTCC 2297 was also shown. Based on the results obtained
by gas chromatography-mass spectroscopy (GC-MS) and thin-layer chromatography
direct bioautography (TLC-DB), it was concluded that triterpenes and flavonoid
compounds found in the three plant extracts could have QS-I activity.
SIGNIFICANCE AND IMPACT OF THE STUDY: A novel alternative prospect to prevent
bacterial infections without inhibiting the growth is to apply chemicals that
inhibit quorum sensing mechanism of the pathogens. Antiquorum property of 61
medicinal plants was evaluated by the ability of their leaf extract(s) to inhibit
production of pigment (violacein in Chromobacterium violaceum MTCC 2656,
pyocyanin in Pseudomonas aeruginosa MTCC 2297) or swarming in P. aeruginosa MTCC
2297. The most prospective plants (for the development of quorum sensing
inhibitor), showing inhibition of violacein production without affecting
bacterial growth, were Astilbe rivularis, Fragaria nubicola and Osbeckia
nepalensis.
PMID- 28421613
TI - Intoxication-Related Alcohol Mixed with Energy Drink Expectancies Scale: Initial
Development and Validation.
AB - BACKGROUND: Young adult use of alcohol mixed with energy drinks (AmEDs) has been
linked with elevated risks of a constellation of problem behaviors. These risks
may be conditioned by expectancies regarding the effects of caffeine in
conjunction with alcohol consumption. The aim of this study was to describe the
construction and psychometric evaluation of the Intoxication-Related AmED
Expectancies Scale (AmED_EXPI), 15 self-report items measuring beliefs about how
the experience of AmED intoxication differs from the experience of noncaffeinated
alcohol (NCA) intoxication. METHODS: Scale development and testing were conducted
using data from a U.S. national sample of 3,105 adolescents and emerging adults
aged 13 to 25. Exploratory and confirmatory factor analyses were conducted to
evaluate the factor structure and establish factor invariance across gender, age,
and prior experience with AmED use. Cross-sectional and longitudinal analyses
examining correlates of AmED use were used to assess construct and predictive
validity. RESULTS: In confirmatory factor analyses, fit indices for the
hypothesized 4-factor structure (i.e., Intoxication Management [IM], Alertness
[AL], Sociability [SO], and Jitters [JT]) revealed a moderately good fit to the
data. Together, these factors accounted for 75.3% of total variance. The factor
structure was stable across male/female, teen/young adult, and AmED experience/no
experience subgroups. The resultant unit-weighted subscales showed strong
internal consistency and satisfactory convergent validity. Baseline scores on the
IM, SO, and JT subscales predicted changes in AmED use over a subsequent 3-month
period. CONCLUSIONS: The AmED_EXPI appears to be a reliable and valid tool for
measuring expectancies about the effects of caffeine during alcohol intoxication.
PMID- 28421614
TI - A first look at the effects of long inter-pregnancy interval and advanced
maternal age on perinatal outcomes: A retrospective cohort study.
AB - BACKGROUND: After China's One-child Policy was replaced with the Two-child Policy
in 2013, the rate of second pregnancies with a longer inter-pregnancy interval
(IPI) has suddenly increased in that country; however, the effect of long IPIs
(>=49 months) on perinatal outcomes remains unreported. METHODS: This was a
retrospective cohort study in China from July 2015 through June 2016. We used
univariate and multivariate logistic regression models to test the associations
among IPI, maternal age, and perinatal outcome (preterm delivery, term low
birthweight, and small-for-gestational age). We included baseline factors and
variables with biological plausibility as confounders. RESULTS: Our analytic
sample included 3309 second pregnancies. The mean IPI was 75.36 months. Compared
with second pregnancies with a short IPI of 7-24 months, those with long IPIs had
higher adjusted odds ratios (ORs) of preterm delivery (1.70-2.00 [95% CI 1.20
3.33]) and term low birthweight (2.16-2.68 [1.10-6.17]), but not small-for
gestational age. The mean maternal age at current delivery was 32.0 years.
Compared with the reference group (25-29 years), second pregnancies for the
oldest maternal age group (>=35 years) showed no statistically significant
increased ORs for adverse perinatal outcomes. CONCLUSION: Long IPI is a
significant contributor to preterm delivery and term low birthweight. Health care
providers need to pay close attention to preterm delivery prevention and fetal
growth during prenatal care for second pregnancies where the mothers have long
IPIs.
PMID- 28421615
TI - The effects of oat beta-glucan incorporation on the quality, structure, consumer
acceptance and glycaemic response of steamed bread.
AB - : The objective of this study was to evaluate the effects of the incorporation of
oat beta-glucan (ObetaG) on the sensory and nutritional quality of steamed bread.
Wheat flour was substituted with ObetaG at levels varying from 0 g/100 g to 5
g/100 g. The results showed that the products containing 1 g/100 g and 3 g/100 g
ObetaG produced a comparable overall consumer acceptance while a significantly
lower score was given to the product with 5 g/100 g. Nutritionally, the presence
of ObetaG impeded in vitro starch hydrolysis by amylolytic enzymes. More
importantly, the addition of ObetaG up to 5 g/100 g did bring about a lower in
vitro predicted glycaemic index to steamed bread, but it generated insignificant
effects on the in vivo glycaemic response. The current work first demonstrated
the feasibility of fabricating ObetaG-enriched steamed bread and its nutritional
superiority compared to the corresponding normal product. PRACTICAL APPLICATIONS:
Modern methods of food elaboration and processing frequently reduce the content
of dietary fiber (DF). Despite the well-known health benefits of DF consumption,
average intake levels still fall far below recommended ones. Oat beta-glucan
(ObetaG) is a kind of indigestible polysaccharide with diverse bioactivity. This
article evaluated the effects of ObetaG incorporation on quality, structure,
consumer acceptance, and glycaemic response of steamed bread. The addition of
less than 3 g/100 g of ObetaG had negligible effects on the consumer acceptance
of steamed bread. The enrichment at 5 g/100 g indeed deteriorated the consumer
acceptance. Moreover, ObetaG highly lowered the glycaemic response of steamed
bread. The current work first demonstrated the feasibility of fabricating ObetaG
enriched steamed bread and its nutritional superiority compared to the
corresponding normal product. ObetaG enriched steamed bread may offer an
alternative to improve DF intake of residents.
PMID- 28421616
TI - The Validity of the Montgomery-Asberg Depression Rating Scale in an Inpatient
Sample with Alcohol Dependence.
AB - BACKGROUND: The Montgomery-Asberg Depression Rating Scale (MADRS) is commonly
used to examine depressive symptoms in clinical settings, including facilities
treating patients for alcohol addiction. No studies have examined the validity of
the MADRS compared to an established clinical diagnostic tool of depression in
this population. This study aimed to examine the following: (i) the validity of
the MADRS compared to a clinical diagnosis of a depressive disorder (using the
Structured Clinical Interview for DSM-IV-TR [SCID-IV-TR]) in patients seeking
treatment for alcohol dependence (AD); (ii) whether the validity of the MADRS
differs by type of SCID-IV-TR-based diagnosis of depression; and (iii) which
items contribute to the optimal predictive model of the MADRS compared to a SCID
IV-TR diagnosis of a depressive disorder. METHODS: Individuals seeking treatment
for AD and admitted to an inpatient unit were administered the MADRS at day 2 of
their detoxification program. Clinical diagnoses of AD and depression were made
via the SCID-IV-TR at the beginning of treatment. RESULTS: In total, 803
participants were included in the study. The MADRS demonstrated low overall
accuracy relative to the clinical diagnosis of depression with an area under the
receiver operating characteristic curve of 0.68. The optimal threshold for
balancing sensitivity and specificity identified by the Euclidean distance was
>14. This cut-point demonstrated a sensitivity of 66%, a specificity of 60%, a
positive predictive value of 50%, and a negative predictive value of 75%. The
MADRS performed slightly better for major depressive disorders compared to
alcohol-induced depression. Items related to lassitude, concentration, and
appetite slightly decreased the accuracy of the MADRS. CONCLUSIONS: The MADRS
does not appear to be an appropriate substitute for a diagnostic tool among
alcohol-dependent patients. The MADRS may, however, still be a useful screening
tool assuming careful consideration of cut-points.
PMID- 28421618
TI - Diffusiophoresis of a charged particle in a microtube.
AB - The diffusiophoresis of a charged sphere along the axis of a circular microtube
filled with an electrolyte solution is studied theoretically. The tube wall may
be either nonconductive and impermeable or prescribed with a linear electrolyte
concentration distribution. The electric double layers at the solid surfaces are
thin, but the diffuse-layer polarization effect over the particle surface is
considered. The general solutions to the electrokinetic differential equations
are expressed in spherical and cylindrical coordinates, whereas the boundary
conditions at the particle surface are satisfied by a collocation technique. The
collocation solutions for the diffusiophoretic velocity of the particle, which
are in good agreement with the asymptotic formula derived from a reflection
method, are obtained for various values of the radius ratio and zeta potential
ratio between the particle and the microtube and of other relevant parameters.
The contributions from the diffusioosmotic flow along the tube wall and wall
corrected diffusiophoretic driving force to the particle velocity can be
superimposed due to the linearity. Although the diffusiophoretic velocity in an
uncharged microtube is in general a decreasing function of the particle-to-tube
radius ratio and can reverse its direction, it can increase with increases in
this ratio due to the competition of the wall effects of possible electrochemical
enhancement and hydrodynamic retardation to the particle motion. When the zeta
potentials associated with the tube and particle are equivalent, the
diffusioosmotic flow induced by the tube wall dominates the diffusiophoretic
motion.
PMID- 28421617
TI - Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol
and Marijuana Use in Adolescence: Initial Findings from the National Consortium
on Alcohol and Neurodevelopment in Adolescence Study.
AB - BACKGROUND: Abundant cross-sectional evidence links eveningness (a preference for
later sleep-wake timing) and increased alcohol and drug use among adolescents and
young adults. However, longitudinal studies are needed to examine whether
eveningness is a risk factor for subsequent alcohol and drug use, particularly
during adolescence, which is marked by parallel peaks in eveningness and risk for
the onset of alcohol use disorders. This study examined whether eveningness and
other sleep characteristics were associated with concurrent or subsequent
substance involvement in a longitudinal study of adolescents. METHODS:
Participants were 729 adolescents (368 females; age 12 to 21 years) in the
National Consortium on Alcohol and Neurodevelopment in Adolescence study.
Associations between the sleep variables (circadian preference, sleep quality,
daytime sleepiness, sleep timing, and sleep duration) and 3 categorical substance
variables (at-risk alcohol use, alcohol bingeing, and past-year marijuana use
[y/n]) were examined using ordinal and logistic regression with baseline age,
sex, race, ethnicity, socioeconomic status, and psychiatric problems as
covariates. RESULTS: At baseline, greater eveningness was associated with greater
at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later
weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed
similar associations across the 3 substance outcomes at baseline. Greater
baseline eveningness was also prospectively associated with greater bingeing and
past-year use of marijuana at the 1-year follow-up, after covarying for baseline
bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and
shorter baseline weekday sleep duration, were similarly associated with greater
bingeing and past-year use of marijuana at the 1-year follow-up after covarying
for baseline values. CONCLUSIONS: Findings suggest that eveningness and sleep
timing may be under recognized risk factors and future areas of intervention for
adolescent involvement in alcohol and marijuana that should be considered along
with other previously identified sleep factors such as insomnia and insufficient
sleep.
PMID- 28421619
TI - Molecular detection of Chlamydia trachomatis and semen quality of sexual partners
of infertile women.
AB - Chlamydia trachomatis is considered as the bacterium that is more sexually
transmitted as cause of male urethritis, epididymitis, orchitis and infertility.
A total of 116 semen samples of men whose couples are infertile women were
analysed. The quality of the semen was measured by standard procedures
recommended by WHO while C. trachomatis was detected by the PCR assay. Thirty
seven semen samples were positive for C. trachomatis (31.9%). Regarding semen
analysis, no different values were observed between positive and negative samples
to C. trachomatis. However, the presence of leucocytes and erythrocytes suggests
an inflammatory process; however, these were high in negative samples to C.
trachomatis. Furthermore, an association between low seminal volume at 1, 5 ml
and the positivity to C. trachomatis was observed (OR=2, 1; CI95 % 1,16-3,07).
The total semen volume is a contribution by the various accessory glands (this
reflects the secretory activity of the glands); a low semen volume could be due
to an obstruction of the ejaculatory duct or infection of accessory glands by C.
trachomatis. More studies are necessary to identify the causes of a reduced semen
volume.
PMID- 28421620
TI - By our bootstraps: Comparing methods for measuring auditory 40 Hz steady-state
neural activity.
AB - Although the 40 Hz auditory steady-state response (ASSR) is of clinical interest,
the construct validity of EEG and MEG measures of 40 Hz ASSR cortical
microcircuits is unclear. This study evaluated several MEG and EEG metrics by
leveraging findings of (a) an association between the 40 Hz ASSR and age in the
left but not right hemisphere, and (b) right- > left-hemisphere differences in
the strength of the 40 Hz ASSR. The contention is that, if an analysis method
does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere
differences, then the obtained measures likely have low validity. Fifty-three
adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were
collected. ASSR activity was examined as a function of phase similarity
(intertrial coherence) and percent change from baseline (total power). A variety
of head models (spherical and realistic) and a variety of dipole source modeling
strategies (dipole source localization and dipoles fixed to Heschl's gyri) were
compared. Several sensor analysis strategies were also tested. EEG sensor
measures failed to detect left 40 Hz ASSR and age associations or hemisphere
differences. A comparison of MEG and EEG head-source models showed similarity in
the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations,
indicating good construct validity across models. Given a goal of measuring the
40 Hz ASSR cortical microcircuits, a source-modeling approach was shown to be
superior in measuring this construct versus methods that rely on EEG sensor
measures.
PMID- 28421621
TI - Presence of Ganglia and Telocytes in Proximity to Myocardial Sleeve Tissue in the
Porcine Pulmonary Veins Wall.
AB - Ganglia and telocytes were identified inside the porcine pulmonary veins wall
near myocardial sleeve tissue at the atriopulmonary junction. These structures
are reported to play a role in the initiation of pulses from outside the heart,
which potentially can cause cardiac conduction disorders such as atrial
fibrillation. In-depth knowledge on the fine structure of the pulmonary vein wall
is a pre-requisite to better understand the underlying pathophysiology of atrial
fibrillation and the origin and conduction of ectopic pulses. The importance of
pulmonary vein myocardial sleeves as triggering foci for atrial fibrillation has
been shown in human patients. In this context, the fine structure of the
pulmonary vein wall was investigated qualitatively by light and transmission
electron microscopy in the pig, which is a frequently used animal model for
development of new treatment strategies. Additionally, intra and extramural
ganglia, containing telocytes that create a network near the neurone cell bodies,
were identified in pigs. Detailed illustration of the distribution and
organization of tissues and cell types, potentially involved in the origin and
propagation of ectopic stimuli originating from the pulmonary veins, might lead
to a better insight on the actual composition of the tissues affected by ablation
as studied in pigs.
PMID- 28421622
TI - Bayesian inference on mixed-effects location scale models with skew-t
distribution and mismeasured covariates for longitudinal data.
AB - In AIDS studies, heterogeneous between and within subject variations are often
observed on longitudinal endpoints. To accommodate heteroscedasticity in the
longitudinal data, statistical methods have been developed to model the mean and
variance jointly. Most of these methods assume (conditional) normal distributions
for random errors, which is not realistic in practice. In this article, we
propose a Bayesian mixed-effects location scale model with skew-t distribution
and mismeasured covariates for heterogeneous longitudinal data with skewness. The
proposed model captures the between-subject and within-subject (WS) heterogeneity
by modeling the between-subject and WS variations with covariates as well as a
random effect at subject level in the WS variance. Further, the proposed model
also takes into account the covariate measurement errors, and commonly assumed
normal distributions for model errors are substituted by skew-t distribution to
account for skewness. Parameter estimation is carried out in a Bayesian
framework. The proposed method is illustrated with a Multicenter AIDS Cohort
Study. Simulation studies are performed to assess the performance of the proposed
method. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421623
TI - A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine
Transmission as Assessed by [11 C]-(+)-PHNO.
AB - BACKGROUND: Previous positron emission tomography (PET) studies exploring the
effect of acute alcohol on dopamine (DA) levels have yielded inconsistent
results, with only some studies suggesting increased synaptic DA levels after an
alcohol challenge. The D2 /D3 agonist radiotracer, [11 C]-(+)-propyl-hexahydro
naphtho-oxazin ([11 C]-(+)-PHNO), has greater sensitivity to synaptic DA
fluctuation than previously used antagonist radiotracers and is in principle more
suitable for imaging alcohol-induced changes in DA. Its high affinity for the D3
receptor also enables measuring changes in D3 -rich brain areas which have
previously been unexplored. The aim of this study was to investigate whether
alcohol reduces [11 C]-(+)-PHNO binding in the striatum and in D3 -rich extra
striatal areas. METHODS: Eight healthy drinkers underwent 2 [11 C]-(+)-PHNO PET
scans following alcohol and placebo in a randomized, single-blind, crossover
design. [11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions
were compared between the 2 scans. RESULTS: Acute alcohol administration did not
significantly reduce [11 C]-(+)-PHNO binding in either the limbic striatum (d =
0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15).
Similarly, there were no changes in binding in the D3 -rich areas of the ventral
pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15).
However, greater percent change in [11 C]-(+)-PHNO binding (DeltaBPND ) between
scans was related to lower blood alcohol levels. CONCLUSIONS: Using the agonist
radiotracer, [11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is
not associated with robust changes in tracer binding in striatal or extra
striatal regions. However, we found that changes in [11 C]-(+)-PHNO binding
following alcohol are dependent on blood alcohol levels suggesting that increases
in DA may occur at lower stimulating doses. The effect of lower doses of alcohol
on DA warrants further investigation in a larger study.
PMID- 28421624
TI - Bayesian exponential random graph modelling of interhospital patient referral
networks.
AB - Using original data that we have collected on referral relations between 110
hospitals serving a large regional community, we show how recently derived
Bayesian exponential random graph models may be adopted to illuminate core
empirical issues in research on relational coordination among healthcare
organisations. We show how a rigorous Bayesian computation approach supports a
fully probabilistic analytical framework that alleviates well-known problems in
the estimation of model parameters of exponential random graph models. We also
show how the main structural features of interhospital patient referral networks
that prior studies have described can be reproduced with accuracy by specifying
the system of local dependencies that produce - but at the same time are induced
by - decentralised collaborative arrangements between hospitals. Copyright (c)
2017 John Wiley & Sons, Ltd.
PMID- 28421626
TI - Editorial Comment from Dr Teishima and Dr Matsubara to Clinical application of
calculated split renal volume using computed tomography-based renal volumetry
after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic
acid renal scan data.
PMID- 28421625
TI - Factors Affecting Platelet Concentration in Platelet Concentrates from Canine
Blood Donors.
AB - BACKGROUND: Physiologic factors in dogs that might contribute to enhanced
platelet yield in platelet concentrates (PCs) are largely unknown. OBJECTIVE: To
determine whether individual differences in weight, age, preprocessing blood
chemistry, and CBC variables predict the final platelet concentrations in PCs.
Our hypotheses were (1) increased lipemic indices would be positively associated
with increased platelet concentrations in PCs and (2) increased preprocessing
platelet concentrations would be associated with higher platelet concentrations
in the PCs. ANIMALS: All blood donation records of dogs from February 2, 2009
through April 1, 2015 at the University of California-Davis Veterinary Blood Bank
were examined with 104 cases included in this study. METHODS: In this
retrospective study, data were collected from medical records of canine blood
donors. Records were reviewed for internal consistency and accuracy and subjects
were included in the study if donor screening and donation occurred on the same
day and a viable PC was obtained. Univariate and multivariable regressions were
used to test the impact that each variable had on the final platelet
concentration in PCs. RESULTS: Final platelet concentration in PCs was positively
associated with the predonation CBC platelet values (P < .001), lipemic index (P
= .01), and phosphorous levels (P = .001). Collectively these 3 variables
explained 29% of the variance in platelet concentrations in PCs. CONCLUSIONS AND
CLINICAL IMPORTANCE: Future prospective studies are required to determine if
canine blood donations from dogs with lipemia yield PCs with higher platelet
concentrations without negatively affecting other blood components.
PMID- 28421627
TI - Impact of microorganisms, humidity, and temperature on the enantioselective
degradation of imazethapyr in two soils.
AB - Imazethapyr (IM) is a chiral herbicide composed of an (-)-R-enantiomer and an (+)
S-enantiomer with differential herbicidal activity. In this study, the effects of
microbial organisms, humidity, and temperature on the selective degradation of
the (-)-R- and (+)-S-enantiomers of IM were determined in silty loam (SL) and
clay loam (CL) soil with different pH values. The (-)-R-enantiomer of IM was
preferentially degraded in two soils under different microorganism, humidity, and
temperature conditions. The average half-lives of R-IM ranged from 43 to 66.1
days and were significantly shorter (P < 0.05) than those of S-IM, which ranged
from 51.4 to 79.8 days. The enantiomer fraction (EF = (+)-S-enantiomer/((-)-R
enantiomer + (+)-S-enantiomer)) values were used to describe the
enantioselectivity of degradation of IM were >0.5 (P < 0.05) in two unsterilized
soils under different humidity and temperature conditions. The highest EF values
were observed at unsterilized CL soil samples under 50% maximum water-holding
capacity (MWHC) and 25 degrees C environmental conditions. The EF values of the
IM enantiomers were significantly higher (P < 0.05) in CL soils (higher pH =
5.81) and were 0.581 (unsterilized) and 0.575 (50% MWHC; 25 degrees C) compared
with those recorded in SL soil (lower pH = 4.85). In addition, this study
revealed that microbial organisms preferentially utilized the more herbicidal
active IM enantiomer.
PMID- 28421628
TI - Comparison of the nephrotoxic effects of iodixanol versus iohexol in patients
with chronic heart failure undergoing coronary angiography or angioplasty.
AB - OBJECTIVES: The aim of this clinical trial is to compare iodixanol with iohexol
for the incidence of contrast-induced nephropathy in patients with chronic heart
failure with reduced ejection fraction who are currently undergoing coronary
angiography or angioplasty. METHODS: The clinical trial included 220 consecutive
patients with chronic heart failure with reduced ejection fraction undergoing
coronary angiography or angioplasty. Study participants were administered either
iodixanol (n = 110) or iohexol (n = 110). The primary study endpoint was the
incidence of contrast-induced nephropathy within 72 h after the procedure. The
secondary endpoints were to determine the peak increase in serum creatinine
levels and Cystatin C, and the peak decrease in estimated glomerular filtration
rate at 72 h post-contrast medium. RESULTS: Baseline demographic and clinical
characteristics of the patients were similar between the two groups. Our study
showed that the overall incidence of contrast induced nephropathy in patients
with chronic heart failure was 20.9%. The incidence of contrast induced
nephropathy was significantly lower in iodixanol group than in iohexol group
(29.1% vs 12.7%, P = 0.041). The peak increase in serum creatinine levels and the
peak decrease in estimated glomerular filtration rate after the procedure were
statistically significant between the two groups. Moreover, there was
statistically significance in the peak increase of Cystatin C levels after the
procedure. CONCLUSIONS: In patients with chronic heart failure with reduced
ejection fraction who are currently undergoing coronary angiography with or
without percutaneous coronary intervention, the iso-osmolar contrast iodixanol
was associated with a lower incidence of contrast induced nephropathy than low
osmolar contrast iohexol.
PMID- 28421629
TI - Synergistic Effect of a Boron-Doped Carbon-Nanotube-Supported Cu Catalyst for
Selective Hydrogenation of Dimethyl Oxalate to Ethanol.
AB - Heteroatom doping is a promising approach to improve the properties of carbon
materials for customized applications. Herein, a series of Cu catalysts supported
on boron-doped carbon nanotubes (Cu/xB-CNTs) were prepared for the hydrogenation
of dimethyl oxalate (DMO) to ethanol. The structure and chemical properties of
boron-doped catalysts were characterized by XRD, TEM, N2 O pulse adsorption, CO
chemisorption, H2 temperature-programmed reduction, and NH3 temperature
programmed desorption, which revealed that doping boron into CNT supports
improved the Cu dispersion, strengthened the interaction of Cu species with the
CNT support, introduced more surface acid sites, and increased the surface area
of Cu0 and especially Cu+ sites. Consequently, the catalytic activity and
stability of the catalysts were greatly enhanced by boron doping. 100 % DMO
conversion and 78.1 % ethanol selectivity could be achieved over the Cu/1B-CNTs
catalyst, the ethanol selectivity of which was almost 1.7 times higher than that
of the catalyst without boron doping. These results suggest that doping CNTs with
boron is an efficient approach to improve the catalytic performance of CNT-based
catalysts for hydrogenation of DMO. The boron-doped CNT-based catalyst with
improved ethanol selectivity and catalytic stability will be helpful in the
development of efficient Cu catalysts supported on non-silica materials for
selective hydrogenation of DMO to ethanol.
PMID- 28421630
TI - The factor structure of dental fear.
AB - There is limited empirical information as to whether or how stimuli associated
with dental fear can be classified into distinct subtypes. The purpose of the
current study was to develop a descriptive framework for the classification of
dental fear. Data were collected using a survey among Dutch twin families (n =
11,771). The sample was randomly divided into two subsamples of, respectively,
5,920 and 5,851 individuals. An exploratory factor analysis (EFA) was performed
on the first subsample to delineate the multidimensional structure of a set of 28
dental-fear-provoking objects and situations. The second sample was used to
confirm the newly derived model using confirmatory factor analysis (CFA). The EFA
yielded a three-factor solution with 70.7% explained variance pertaining to: (i)
invasive treatment or pain; (ii) losing control; and (iii) physical sensations.
The CFA showed an acceptable fit to the data, thereby confirming the stability of
the three-factor structure. There are at least three different subtypes of dental
fear. As these subtypes require a different treatment approach in clinical
practice, it could be important to assess the severity of patients' fear response
along these three dimensions.
PMID- 28421631
TI - Subclinical lower airways correlates of chronic allergic and non-allergic
rhinitis.
AB - The upper and lower airways behave as a physiological and pathophysiological
unit. Subclinical lower airways abnormalities have been described in patients
with rhinitis without asthma. These are expressed as bronchial hyperreactivity,
abnormalities in lung function and bronchial inflammation, likely as a result of
the same phenomenon with systemic inflammatory impact that reaches both the nose
and the lungs, which for unknown reasons does not always have a full clinical
expression. Patients with rhinitis are at increased risk of developing asthma;
therefore, most authors suggest a careful clinical evaluation and monitoring of
these patients, especially if symptoms related to inflammation in the lower
airways are observed. Although current treatments, such as H1-antihistamines,
intranasal steroids and allergen immunotherapy, are quite effective for the
management of rhinitis, it is difficult to prove their capacity to prevent asthma
among subjects with rhinitis. Evidence showing that the treatment of rhinitis has
a favourable impact on indicators of bronchial hyperreactivity and inflammation
among subjects that have no symptoms of asthma is more frequently described. In
this review, we address the frequency and characteristics of lower airway
abnormalities in subjects with rhinitis, both in paediatric and adult
populations, their likely predictive value for the development of asthma and the
possibilities for therapeutic intervention that could modify the risk of subjects
with rhinitis towards presenting asthma.
PMID- 28421632
TI - Rigidly Tethered Bis-phosphoric Acids: Generation of Tunable Chiral Fluorescent
Frameworks and Unexpected Selectivity for the Detection of Ferric Ions.
AB - We describe the straightforward synthesis of a series of bis-phosphoric acids
(R,R)-1 a-d, featuring two chiral 1,1'-binaphthyl-phosphoric acid units that are
tethered by rigid, pi-conjugated linkers. The nature of the linker has a profound
influence on the properties of the bis-phosphoric acids, such as their self
association behavior and their interaction with metal ions. This led to the
identification of one preferred bis-phosphoric acid (R,R)-1 d, which shows
selective fluorescence quenching in the presence of ferric ions (Fe3+ ). Thus,
(R,R)-1 d could be applied for the detection of Fe3+ , even in the presence of a
variety of other metal ions. The chiral nature of the bis-phosphoric acid enables
the interaction with Fe3+ to be followed by CD spectroscopy, providing a
complementary detection mode with the same probe.
PMID- 28421633
TI - Efficacy of Tulathromycin for the Treatment of Foals with Mild to Moderate
Bronchopneumonia.
AB - BACKGROUND: There is conflicting data regarding the efficacy of tulathromycin for
the treatment of foals with bronchopneumonia. HYPOTHESES: Tulathromycin is
effective for the treatment of bronchopneumonia in foals and noninferior to the
combination of azithromycin and rifampin. ANIMALS: A total of 240 foals on a farm
endemic for infections caused by Rhodococcus equi. METHODS: In a controlled,
randomized, and double-blinded clinical trial, foals with ultrasonographic
pulmonary lesions (abscess score 10-15 cm) were allocated to 3 groups: 1
tulathromycin IM q 7 days (n = 80); 2-azithromycin-rifampin, orally q24h (n =
80); or 3-untreated controls (n = 80). Physical examination and thoracic
ultrasonography were performed by individuals unaware of treatment group
assignment. Foals that worsened were considered treatment failures and removed
from the study. RESULTS: The proportion of foals that recovered was significantly
higher for foals treated with tulathromycin (70 of 79) or azithromycin-rifampin
(76 of 80) compared to that of control foals (22 of 80). The difference in the
percentage of efficacy of azithromycin-rifampin versus tulathromycin was 6.4%
(90% CI = -0.72-13.5%). Given that the confidence interval crossed the
predetermined noninferiority limit of 10%, the null hypothesis that the response
rate in the azithromycin-rifampin group is superior to that of the tulathromycin
group could not be rejected. Resolution of ultrasonographic lesions occurred
faster in foals treated with azithromycin-rifampin than in foals treated with
tulathromycin. CONCLUSION AND CLINICAL IMPORTANCE: Tulathromycin was effective
for the treatment of bronchopneumonia in foals at this farm but not as effective
as the combination of azithromycin-rifampin.
PMID- 28421634
TI - Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel
disease.
AB - Inflammatory bowel disease (IBD), that is Crohn's disease (CD) and ulcerative
colitis, affects about 1.5 million persons in the USA and 2.2 million in Europe.
The pathophysiology of IBD involves immunological, genetic and environmental
factors. The treatment is medico-surgical but suspensive. Anti-TNFalpha agents
have revolutionized the treatment of IBD but have side effects. In addition, a
non-negligible percentage of patients with IBD stop or take episodically their
treatment. Consequently, a nondrug therapy targeting TNFalpha through a
physiological pathway, devoid of major side effects and with a good cost
effectiveness ratio, would be of interest. The vagus nerve has dual anti
inflammatory properties through its afferent (i.e. hypothalamic-pituitary-adrenal
axis) and efferent (i.e. the anti-TNFalpha effect of the cholinergic anti
inflammatory pathway) fibres. We have shown that there is an inverse relationship
between vagal tone and plasma TNFalpha level in patients with CD, and have
reported, for the first time, that chronic vagus nerve stimulation has anti
inflammatory properties in a rat model of colitis and in a pilot study performed
in seven patients with moderate CD. Two of these patients failed to improve after
3 months of vagus nerve stimulation but five were in deep remission (clinical,
biological and endoscopic) at 6 months of follow-up and vagal tone was restored.
No major side effects were observed. Thus, vagus nerve stimulation provides a new
therapeutic option in the treatment of CD.
PMID- 28421635
TI - A Homochiral {CoIotaIota16 CoIotaIotaIota4 } Supertetrahedral T4 Cluster from a
Racemic Ligand with Ferromagnetic Behavior and High Photocatalytic Activity.
AB - A homochiral mixed-valence cobalt cluster [CoIotaIota16 CoIotaIotaIota4 (MU6 -O)4
(MU3 -OH)12 (S-bme)12 (OAc)6 ]Cl6 ?5 CH3 OH?18 H2 O (1, Hbme=1H-(benzimidazol-2
yl)ethanol) was synthesized from a racemic ligand and three cobalt salts of CoCl2
?6 H2 O, Co(Ac)2 ?4 H2 O and Co(NO3 )2 ?6 H2 O in a DMF/MeOH mixed solvent. The
enantioselective coordination occurs when a large excess of cobalt ions added in
the solution and only the S-configuration of the racemic ligand involved in
crystallization. The CD spectra of three crystal samples show identical Cotton
signals, indicating the repeatability and the enantiomeric purity of the single
crystals. This compound presents a beautiful two-shell Matryoshka-type
supertetrahedral T4 cluster constructed by an inner CoIotaIotaIota4 O4 cubane and
four exterior CoIotaIota4 O4 cubanes bridged by MU6 -O2- and MU3 -OH- ions. This
highest nuclear chiral cobalt cluster is the first example of enantiopure cobalt
cluster separated from a racemic ligand and is the largest supertetrahedral
cobalt cluster up to now. The magnetic studies reveal it behaves as a
ferromagnet. Photocatalytic properties of 1 show high catalytic activities for
the degradation of the highly toxic triphenyl dye crystal violet (CV) in the
presence of H2 O2 under visible light in aqueous solution. The degradation rate
almost reach 100 % at 45 min and can maintain 98.54 % after 8 cycles.
PMID- 28421636
TI - Leveraging cell type specific regulatory regions to detect SNPs associated with
tissue factor pathway inhibitor plasma levels.
AB - Tissue factor pathway inhibitor (TFPI) regulates the formation of intravascular
blood clots, which manifest clinically as ischemic heart disease, ischemic
stroke, and venous thromboembolism (VTE). TFPI plasma levels are heritable, but
the genetics underlying TFPI plasma level variability are poorly understood.
Herein we report the first genome-wide association scan (GWAS) of TFPI plasma
levels, conducted in 251 individuals from five extended French-Canadian Families
ascertained on VTE. To improve discovery, we also applied a hypothesis-driven
(HD) GWAS approach that prioritized single nucleotide polymorphisms (SNPs) in (1)
hemostasis pathway genes, and (2) vascular endothelial cell (EC) regulatory
regions, which are among the highest expressers of TFPI. Our GWAS identified 131
SNPs with suggestive evidence of association (P-value < 5 * 10-8 ), but no SNPs
reached the genome-wide threshold for statistical significance. Hemostasis
pathway genes were not enriched for TFPI plasma level associated SNPs (global
hypothesis test P-value = 0.147), but EC regulatory regions contained more TFPI
plasma level associated SNPs than expected by chance (global hypothesis test P
value = 0.046). We therefore stratified our genome-wide SNPs, prioritizing those
in EC regulatory regions via stratified false discovery rate (sFDR) control, and
reranked the SNPs by q-value. The minimum q-value was 0.27, and the top-ranked
SNPs did not show association evidence in the MARTHA replication sample of 1,033
unrelated VTE cases. Although this study did not result in new loci for TFPI, our
work lays out a strategy to utilize epigenomic data in prioritization schemes for
future GWAS studies.
PMID- 28421637
TI - A New Approach to Models of the 4,5-Dihydroxycyclopentenone Core of the
Kodaistatins A-D: Elucidation of the Diol Configuration in Kodaistatin A.
AB - The kodaistatins A-D are strongly anti-diabetic natural products from Aspergillus
terreus that hold some promise of a novel diabetes cure. However, considerations
of that kind face two drawbacks: 1) The kodaistatins A-D contain a heavily
substituted pulvinone/cyclopentenone combination; 2) they are 1,2-diols, the 3D
structures of which have not been assigned yet. However, we can exclude two of
the four possible stereostructures. We conclude that kodaistatin A is a trans-,
not a cis-diol from NMR comparisons with a pair of cis, trans-isomeric
kodaistatin models, which we synthesized in 11 and 12 steps, respectively. The
stereocenters of the diol moiety arose from stereocomplementary, highly
diastereoselective aldol additions of a lithium enolate or the corresponding
silyl ketene acetal. The cyclopentenone moieties stemmed from intramolecular
aldol additions and ensuing dehydrations. The requisite enolates were obtained by
the reduction of alpha-bromoketones with samarium diiodide.
PMID- 28421638
TI - Renal Replacement Therapy and Incremental Hemodialysis for Veterans with Advanced
Chronic Kidney Disease.
AB - Each year approximately 13,000 Veterans transition to maintenance dialysis,
mostly in the traditional form of thrice-weekly hemodialysis from the start.
Among >6000 dialysis units nationwide, there are currently approximately 70
Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers
and their limited capacity, only 10% of all incident dialysis Veterans initiate
treatment in a VA center. Evidence suggests that, among Veterans, the receipt of
care within the VA system is associated with favorable outcomes, potentially
because of the enhanced access to healthcare resources. Data from the United
States Renal Data System Special Study Center "Transition-of-Care-in-CKD" suggest
that Veterans who receive dialysis in a VA unit exhibit greater survival compared
with the non-VA centers. Substantial financial expenditures arise from the high
volume of outsourced care and higher dialysis reimbursement paid by the VA than
by Medicare to outsourced providers. Given the exceedingly high mortality and
abrupt decline in residual kidney function (RKF) in the first dialysis year, it
is possible that incremental transition to dialysis through an initial twice
weekly hemodialysis regimen might preserve RKF, prolong vascular access
longevity, improve patients' quality of life, and be a more patient-centered
approach, more consistent with "personalized" dialysis. Broad implementation of
incremental dialysis might also result in more Veterans receiving care within a
VA dialysis unit. Controlled trials are needed to examine the safety and efficacy
of incremental hemodialysis in Veterans and other populations; the administrative
and health care as well as provider structure within the VA system would
facilitate the performance of such trials.
PMID- 28421639
TI - Cilostazol adjunctive therapy in treatment of negative symptoms in chronic
schizophrenia: Randomized, double-blind, placebo-controlled study.
AB - OBJECTIVE: To evaluate the efficacy and safety of cilostazol, a selective
inhibitor of phosphodiesterase III, as an adjunctive to risperidone in
alleviating the negative symptoms of schizophrenia. METHODS: Eighty-four in
patients with diagnosis of chronic schizophrenia participated in a randomized,
placebo-controlled trial and underwent 8 weeks of treatment with either
cilostazol (50 mg twice a day) or placebo as an adjuvant to risperidone.
Participants were assessed using the positive and negative syndrome scale (PANSS)
at baseline and at weeks 2, 4, 6, and 8. The primary outcome measure of the trial
was to evaluate the efficacy of cilostazol compared to placebo in improving the
PANSS negative subscale score. RESULT: General linear model repeated measures
demonstrated significant effect for time * treatment interaction on negative
subscale scores (p < .001) and PANSS total (p = .006) but did not demonstrate
significant effect on the PANSS positive (p = .37) and general (p = .06)
subscales. Frequency of adverse events was not significantly different between
the 2 treatment groups. No serious adverse event was observed. CONCLUSION: An 8
week course of treatment with cilostazol as an adjunct to risperidone showed a
favorable safety and efficacy profile in patients with schizophrenia.
PMID- 28421640
TI - Identification of risk factors predicting febrile neutropenia in patients with
metastatic germ cell tumors receiving cisplatin-based combination chemotherapy.
AB - OBJECTIVES: To identify clinical features and predictive factors of febrile
neutropenia in Japanese patients with metastatic germ cell tumors undergoing
cytotoxic chemotherapy. METHODS: Between April 2007 and May 2016, 86 consecutive
Japanese patients with metastatic germ cell tumors were treated with cisplatin
based combination chemotherapy, including bleomycin, etoposide and cisplatin, and
paclitaxel, ifosfamide and cisplatin. A total of 378 chemotherapy cycles
administered for these 86 patients were retrospectively analyzed. RESULTS: During
the 378 cycles, consisting of 212 for bleomycin, etoposide and cisplatin, and 166
for paclitaxel, ifosfamide and cisplatin, 81 episodes of febrile neutropenia
(21.4%) developed in 34 patients (39.5%). Multivariate logistic regression
analysis showed that low estimated glomerular filtration rate and albumin levels
were independent risk factors for the development of febrile neutropenia.
Furthermore, a significant difference in the incidence of febrile neutropenia was
noted according to positive numbers of these two independent risk factors; that
is, febrile neutropenia occurred in 13 of 171 courses in patients negative for
any risk factors (7.6%), 44 of 155 courses in those positive for a single risk
factor (28.4%) and 24 of 52 courses in those positive for two risk factors
(46.2%). CONCLUSIONS: The incidence of febrile neutropenia in Japanese metastatic
germ cell tumor patients receiving cisplatin-based combination chemotherapy
appears to be higher than reported previously by studies in Western countries.
When carrying out cytotoxic chemotherapy, special attention should be paid to
patients with low estimated glomerular filtration rate and/or albumin levels
considering the high probability of febrile neutropenia.
PMID- 28421641
TI - It is not just about occupation, but also about where you work.
AB - OBJECTIVES: Dentistry is characterized by a meaningful but also stressful
psychosocial working environment. Job satisfaction varies among staff working
under different organizational forms. The aim of this study was to identify (i)
to what extent crucial psychosocial work environment characteristics differ among
occupations in general public dental clinics in Sweden, and (ii) how much of the
variation within each occupation is attributable to the organizational level.
METHODS: All staff (N=1782) employed in four public dental organizations received
an email with personal log-in to an electronic questionnaire based on the
Copenhagen Psychosocial Questionnaire. After two reminders, a response rate of
75% was obtained. Responses from 880 nonmanagerial dentists, dental hygienists
and dental nurses working in general practices were included in our analyses.
RESULTS: First, we compared the three dental occupations. We found that job
demands, task resources (eg influence, possibilities for development and role
clarity), strain symptoms and attitudes to work differed among occupations,
dentists having the least favourable situation. Next, we compared the four
organizations for each occupational group, separately. For dentists, a
significant and relevant amount of variance (P<.05 and ICC >.05) was explained by
the organizational level for 15 of 26 subscales, least pronounced for task
resources. By contrast, for dental nurses and hygienists, the corresponding
number was 2 subscales of 26. The psychosocial working environment of people
working at the organization with the highest levels of strain indicators and the
least positive work-related attitudes differed systematically from the
organization with the most favourable profile, in particular regarding job
demands and leadership aspects. CONCLUSION: In conclusion, the psychosocial
working environment depended to a large degree on occupation and, for dentists in
particular, also on their organizational affiliation. The findings suggest a
potential for designing interventions at organizational level for improvements of
the psychosocial working environment for dentists.
PMID- 28421642
TI - How do we know what makes for "best practice" in clinical supervision for
psychological therapists? A content analysis of supervisory models and
approaches.
AB - : Clinical supervision for psychotherapies is widely used in clinical and
research contexts. Supervision is often assumed to ensure therapy adherence and
positive client outcomes, but there is little empirical research to support this
contention. Regardless, there are numerous supervision models, but it is not
known how consistent their recommendations are. This review aimed to identify
which aspects of supervision are consistent across models, and which are not. A
content analysis of 52 models revealed 71 supervisory elements. Models focus more
on supervisee learning and/or development (88.46%), but less on emotional aspects
of work (61.54%) or managerial or ethical responsibilities (57.69%). Most models
focused on the supervisee (94.23%) and supervisor (80.77%), rather than the
client (48.08%) or monitoring client outcomes (13.46%). Finally, none of the
models were clearly or adequately empirically based. Although we might expect
clinical supervision to contribute to positive client outcomes, the existing
models have limited client focus and are inconsistent. Therefore, it is not
currently recommended that one should assume that the use of such models will
ensure consistent clinician practice or positive therapeutic outcomes. KEY
PRACTITIONER MESSAGES: There is little evidence for the effectiveness of
supervision. There is a lack of consistency in supervision models. Services need
to assess whether supervision is effective for practitioners and patients.
PMID- 28421643
TI - Empiric antibiotic regimens for neonatal sepsis in Australian and New Zealand
neonatal intensive care units.
AB - AIM: Neonatal sepsis remains an important cause of morbidity and mortality, and
requires prompt empiric treatment. However, only a minority of babies who receive
antibiotics for suspected sepsis have an infection. Antimicrobial exposure in
infancy has important short- and long-term consequences. There is no consensus
regarding empirical antimicrobial regimens. METHODS: The study included a survey
of empiric antimicrobial regimens in all tertiary neonatal intensive care units
in Australia and New Zealand in 2013-2014. RESULTS: All 27 units responded. For
early-onset sepsis, all units used a combination of gentamicin with either
penicillin or ampicillin. For late-onset sepsis, the frequency of units using
empiric vancomycin (41%) versus empiric flucloxacillin (48%) was similar.
Gestational age or the presence of a central venous catheter had little influence
on using vancomycin instead of flucloxacillin. For late-onset sepsis with
meningitis there was marked variation in antimicrobial combinations, with 15
different regimens described. A total of 93% used a cefotaxime-based regimen,
either as monotherapy (22%) or combined with a second (22%) or third (48%) agent.
For suspected necrotising enterocolitis, 89% used an aminoglycoside,
metronidazole and a penicillin. Historical outbreaks of multi-resistant organisms
exerted long-term influence over regimen choice. CONCLUSIONS: There was limited
use of broad-spectrum agents such as carbapenems or third-generation
cephalosporins. In this region with low methicillin-resistant Staphylococcus
aureus prevalence, empiric vancomycin use was common, selected for activity
against coagulase-negative staphylococci. Empiric vancomycin is rarely necessary
because coagulase-negative staphylococci are often contaminants and sepsis is
rarely fulminant, occurring almost exclusively in extremely low birthweight
infants. Implementation of appropriate, local antimicrobial policies is crucial
to minimise antimicrobial exposure in this vulnerable population and halt the
development of antimicrobial resistance.
PMID- 28421644
TI - The clinical application of suicide risk assessment: A theory-driven approach.
AB - : The interpersonal theory of suicide posits that thwarted belongingness (TB) and
perceived burdensomeness (PB) increase suicide ideation; however, studies have
found mixed results regarding this hypothesis among psychiatric inpatients. This
study aimed to (a) demonstrate how assessing TB and PB using the Interpersonal
Needs Questionnaire (INQ) can provide clinically useful information and (b)
investigate how statistical methodology may impact the clinical application of
the INQ. Participants were 139 (Sample 1) and 104 (Sample 2) psychiatric
inpatients. In both samples, ordinal logistic regression results indicated TB and
PB, separately, were significant predictors of suicide ideation-related outcomes;
however, when examined as simultaneous predictors, TB was no longer a significant
predictor. The interaction between TB and PB was not significant for either
sample. Despite this, TB and PB scores provided clinically relevant information
about suicide ideation-related outcomes. For example, the highest scores on TB
and PB indicated a 93% and 95% chance of having some level of distress due to
suicide ideation (Sample 1), a 91% and 92% chance of having some level of desire
for death, and a 79% and 84% chance of having some level of desire for suicide,
respectively (Sample 2). This study also proposes clinical cutoff scores for the
INQ (for TB and PB, respectively, cutoff scores were 22 and 17 for distress due
to suicide ideation, 33 and 17 for desire for death, and 31 and 22 for desire for
suicide). Although these results indicate that multicollinearity between TB and
PB may create interpretational ambiguity for clinicians, TB and PB may each be
useful separate predictors of suicide ideation-related outcomes in psychiatric
inpatient settings and should be incorporated into suicide risk assessment. KEY
PRACTITIONER MESSAGE: The 15-item Interpersonal Needs Questionnaire (an
assessment of thwarted belongingness and perceived burdensomeness) should be
incorporated into suicide risk assessment. Among psychiatric inpatients, greater
thwarted belongingness and perceived burdensomeness, as separate predictors, were
associated with increased levels of distress due to suicide ideation, desire for
death, and desire for suicide. The highest scores on thwarted belongingness and
perceived burdensomeness indicated a 79% to 95% chance of experiencing an
elevated level of distress due to suicide ideation, desire for death, or desire
for suicide. Recommended clinical cutoff scores were provided. For example,
thwarted belongingness cutoff score of 31 and perceived burdensomeness cutoff
score of 22 maximized the sensitivity and specificity of the INQ to detect some
level of desire for suicide.
PMID- 28421645
TI - Grammaticality differences between Spanish-speaking children with specific
language impairment and their typically developing peers.
AB - BACKGROUND: A limited number of studies have analyzed grammaticality in
monolingual Spanish-speaking children with specific language impairment (SLI).
Most of the available data are based on bilingual speakers. AIMS: To extend
previous studies by doing a more detailed analysis of grammatical types in
monolingual Spanish-speakers with and without SLI. METHODS & PROCEDURES: Forty
nine Spanish-speaking children (18 with SLI, 17 age-matched typically developing
controls, 14 language-matched controls) were recruited from schools in Mexico and
observed in a spontaneous narrative task. OUTCOMES & RESULTS: The findings were
inconsistent with those of previous studies. Significant differences were found
for article, connector and preposition omissions, and the per cent of
ungrammatical utterances. There were no significant differences found for clitics
and verb phrases, though clitic substitutions were frequent. Language-matched
controls did not produce different frequencies of ungrammatical utterances.
CONCLUSIONS & IMPLICATIONS: Significant differences were found for three main
items: the per cent of ungrammatical utterances, the omission of articles and the
omission of prepositions. Therefore, we propose these components be taken into
consideration when distinguishing typically developing children from children
with SLI.
PMID- 28421646
TI - Increasing adolescents' depth of understanding of cross-curriculum words: an
intervention study.
AB - BACKGROUND: There is some evidence that vocabulary intervention is effective for
children, although further research is needed to confirm the impact of
intervention within contexts of social disadvantage. Very little is known about
the effectiveness of interventions to increase adolescent knowledge of cross
curriculum words. AIMS: To evaluate the effectiveness of an intervention
programme designed to develop adolescents' knowledge of cross-curriculum words.
METHODS & PROCEDURES: Participants were 35 adolescents aged between 12 and 14
years who were at risk of educational underachievement with low scores on a range
of assessments. Participants received a 10-week intervention programme in small
groups, targeting 10 cross-curriculum words (e.g., 'summarize'). This was
evaluated using a bespoke outcome measure (the Word Knowledge Profile). The study
involved an AABA design, with a repeated baseline, delayed intervention cohort
and blind assessment. Intervention included both semantic and phonological
information about the target words and involved the adolescents using the words
in multiple contexts. OUTCOMES & RESULTS: Results were promising and
participants' knowledge of the targeted words significantly increased following
intervention. Progress was demonstrated on the Word Knowledge Profile on the item
requiring participants to define the word (for the summer intervention group
only). This increase in depth of knowledge was seen on taught words but not on
matched non-taught words. CONCLUSIONS & IMPLICATIONS: Cross-curriculum words are
not consistently understood by adolescents at risk of low educational attainment
within a low socio-economic context. A 10-week intervention programme resulted in
some increases to the depth of knowledge of targeted cross-curriculum words.
PMID- 28421647
TI - Evaluation of magnetic resonance imaging for the differentiation of inflammatory,
neoplastic, and vascular intradural spinal cord diseases in the dog.
AB - Magnetic resonance imaging (MRI) is a common test for dogs with suspected
intradural spinal cord lesions, however studies on diagnostic performance for
this test are lacking. Objectives of this multi-institutional, retrospective,
case-control study were to estimate sensitivity and specificity of MRI for (1)
distinguishing between histopathologically confirmed intradural spinal cord
disease versus degenerative myelopathy in dogs, (2) categorizing intradural
spinal cord diseases as neoplastic, inflammatory, or vascular; and (3)
determining tumor type within the etiologic category of neoplasia. Additional
aims were to (1) determine whether knowledge of clinical data affects sensitivity
and specificity of MRI diagnoses; and (2) report interrater agreement for MRI
classification of intradural spinal lesions. Cases were recruited from
participating hospital databases over a 7-year period. Three reviewers
independently evaluated each MRI study prior to and after provision of clinical
information. A total of 87 cases were sampled (17 degenerative myelopathy, 53
neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had
excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions
but specificity varied before and after provision of clinical data (68.6% vs.
82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and
moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower
for classifying inflammatory lesions but improved with provision of clinical data
(48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for
diagnosing vascular lesions (25.0%). Interrater agreement was very good for
correctly diagnosing dogs with intradural lesions (K = 0.882-0.833), and good (K
= 0.726-0.671) for diagnosing dogs with neoplasia.
PMID- 28421648
TI - Placebo-like analgesia via response imagery.
AB - BACKGROUND: Placebo effects on pain are reliably observed in the literature. A
core mechanism of these effects is response expectancies. Response expectancies
can be formed by instructions, prior experiences and observation of others.
Whether mental imagery of a response can also induce placebo-like expectancy
effects on pain has not yet been studied systematically. METHODS: In Study 1, 80
healthy participants were randomly allocated to (i) response imagery or (ii)
control imagery. In Study 2, 135 healthy participants were randomly allocated to
(i) response imagery with a verbal suggestion regarding its effectiveness, (ii)
response imagery only, or (iii) no intervention. In both studies, expected and
experienced pain during cold pressor tests were measured pre- and post
intervention, along with psychological and physiological measures. RESULTS:
Participants rated pain as less intense after response imagery than after control
imagery in Study 1 (p = 0.044, etap2 = 0.054) and as less intense after response
imagery (with or without verbal suggestion) than after no imagery in Study 2 (p <
0.001, etap2 = 0.154). Adding a verbal suggestion did not affect pain (p = 0.068,
etap2 = 0.038). The effects of response imagery on experienced pain were mediated
by expected pain. CONCLUSIONS: Thus, in line with research on placebo effects,
the current findings indicate that response imagery can induce analgesia, via its
effects on response expectancies. SIGNIFICANCE: The reported studies extend
research on placebo effects by demonstrating that mental imagery of reduced pain
can induce placebo-like expectancy effects on pain.
PMID- 28421649
TI - Decreased expression of EphA5 is associated with Fuhrman nuclear grade and
pathological tumour stage in ccRCC.
AB - The incidence of renal cell carcinoma is increasing all over the world. The
molecular mechanisms for tumorigenesis, progression and prognosis are still
unknown. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors
have been reported to be expressed aberrantly in many types of human cancers and
in particular EphA5 may play a role in certain human cancers. In this study, a
set of clear cell renal cell carcinoma (ccRCC) tissues were subjected to
immunohistochemistry. The relationship between EphA5 protein expression and
clinicopathological parameters was statistically analysed. Our data show that
EphA5 protein was negatively (0) or weakly (1+) expressed in 48 of 78 (61.5%),
moderately (2+) expressed in 15 of 78 (19.2%) and strongly (3+) expressed in 15
of 78 (19.2%) tumour samples of ccRCC. Decreased expression of EphA5 was detected
more often in females than in males (P = 0.017, rs = -0.267). Expression of
EphA5 was related negatively to Fuhrman grade (P = 0.013, rs = -0.279) and
pathological tumour stage pT (P = 0.003, rs = -0.334). No relation between the
expression of EphA5 and age of patients was found (P = 0.107, rs = 0.184).
Fuhrman grade and pT stage are the most important factors used in prognosis of
ccRCC. Hence this study may provide a new and useful prognostic marker in the
clinical practice of ccRCC.
PMID- 28421650
TI - Keeping Up With the Kids: Diffusion of Innovation in Pediatric Emergency Medicine
Among Emergency Physicians.
PMID- 28421652
TI - Corrigendum.
PMID- 28421651
TI - Self-management of first trimester medical termination of pregnancy: a
qualitative study of women's experiences.
AB - OBJECTIVE: To explore the experiences of women in Scotland who return home to
complete medical termination of pregnancy (TOP) <=63 days of gestation, after
being administered with mifepristone and misoprostol at an NHS TOP clinic.
DESIGN: Qualitative interview study. SETTING: One National Health Service health
board (administrative) area in Scotland. POPULATION OR SAMPLE: Women in Scotland
who had undergone medical TOP <=63 days, and self-managed passing the pregnancy
at home; recruited from three clinics in one NHS health board area between
January and July 2014. METHODS: In-depth, semi-structured interviews with 44
women in Scotland who had recently undergone TOP <=63 days of gestation, and who
returned home to pass the pregnancy. Data were analysed thematically using an
approach informed by the Framework method. MAIN OUTCOME MEASURES: Women's
experiences of self-management of TOP <=63 days of gestation. RESULTS: Key themes
emerging from the analysis related to self-administration of misoprostol in
clinic; reasons for choosing home self-management; facilitation of self
management and expectation-setting; experiences of getting home; self-managing
and monitoring treatment progress; support for self-management (in person and
remotely); and pregnancy self-testing to confirm completion. CONCLUSIONS:
Participants primarily found self-administration of misoprostol and home self
management to be acceptable and/or preferable, particularly where this was
experienced as a decision made jointly with health professionals. The way in
which home self-management is presented to women at clinic requires ongoing
attention. Women could benefit from the option of home administration of
misoprostol. TWEETABLE ABSTRACT: Women undergoing medical TOP 63 days found home
self-management to be acceptable and/or preferable.
PMID- 28421653
TI - Permethrin and malathion LD90 values for Culex quinquefasciatus vary with topical
application site.
AB - Prior research in multiple insect species has demonstrated that insecticide
induced mortality varies according to the body region exposed on the insect. This
variation has been demonstrated in Culex quinquefasciatus Say (Diptera:
Culicidae), but has not been quantified using dose-response curves. Applications
of technical permethrin or malathion to one of three body regions on Cx.
quinquefasciatus resulted in dose-response curves that were not equivalent to one
another. The generated LD90 values and curves for each body region were compared
with previously reported LD values for analogous sites in several mosquito
species, specifically the mesothorax. Based on the present results, the
permethrin and malathion LD50 and LD90 concentrations required for droplets
impinging on the abdomen and mesothorax of Cx. quinquefasciatus when applied
through ground-based spray systems utilized by mosquito control programmes were
calculated.
PMID- 28421655
TI - Reduction of preterm birth rates starts at preconception.
PMID- 28421654
TI - Short-term outcomes of small incision cataract surgery provided by a regional
population in the Pacific.
AB - BACKGROUND: This study aims to describe patient demographics, visual and surgical
outcomes of a cohort undergoing small incision cataract surgery at a Pacific
regional ophthalmic training facility. DESIGN: This is a prospective,
longitudinal study conducted at the Pacific Eye Institute, Fiji. PARTICIPANTS:
One hundred fifty-six patients underwent small incision cataract surgery.
METHODS: Preoperatively, a complete ophthalmic examination, including pachymetry
and macular optical coherence tomography performed by two independent
investigators. Temporal small incision cataract surgery with intraocular lens
insertion was performed by ophthalmologists, and trainee ophthalmologists. Follow
up occurred at day one, four weeks and 3 months. MAIN OUTCOME MEASURES: Patient
characteristics, visual outcomes including surgically induced astigmatism and
complications. RESULTS: Ninety-one per cent (142/156) attended 3-month follow-up
with median age 63 years (range 19-82), 52% female (81/156) and 58% (90/156)
Fijian ethnicity. In 37% (57/156), the contralateral eye was pseudophakic. Mean
preoperative best spectacle-corrected visual acuity was logMAR 1.44 (6/165). At 3
months, 74% (105/142) achieved >=6/18 unaided vision (94% [133/142] best
spectacle-corrected visual acuity). Mean postoperative spherical equivalent was
0.78 (SD 0.95) D and mean surgically induced astigmatism 1.04 (0.57) D.
Complications included posterior capsular rupture with vitreous loss (4%
[6/156]), optical coherence tomography confirmed macular oedema (8% [12/152] at 4
weeks), significant posterior capsular opacity (23% [31/136]) and >5% increase in
preoperative pachymetry (1% [1/142]) at 3 months. Reduction in preoperative best
spectacle-corrected visual acuity occurred in 2% (3/142). No cases of
endophthalmitis. CONCLUSION AND RELEVANCE: Small incision cataract surgery
provided to a regional population is effective with 94% achieving the World
Health Organisation's definition of 'Good Vision' (>=6/18). Refinements in
biometric and surgical techniques may allow a greater proportion of patients to
achieve good unaided vision.
PMID- 28421656
TI - Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and
wrinkling: A randomized, double-blind, and placebo-controlled study.
AB - BACKGROUND: Photoaging is a severe skin damage that occurs as a result of
exposure to external elements, primarily ultraviolet (UV) irradiation.
Chronically, UV-irradiated skin exhibits the signs of sunburn and
hyperpigmentation with the destruction of connective tissues. Previously,
Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed
antiphotoaging activities in vitro and in vivo. OBJECTIVE: The aim of this study
was to investigate the clinical efficacy of B. pandurata intake on skin
hydration, gloss, wrinkling, and elasticity. METHODS: A double-blind, placebo
controlled trial was conducted to clinically evaluate the effect of B. pandurata
ethanol extract (BPE) containing 8% of panduratin A on human skin hydration,
gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to
receive tablets containing either BPE or placebo for 12 weeks. RESULTS: The test
group had significantly increased skin hydration and gloss and decreased
wrinkling compared to the placebo group at 12 weeks. There was no significant
difference in skin elasticity between the two groups; however, the increment rate
in the test group was higher than that in the placebo group at 12 weeks. None of
the subjects developed adverse symptoms during the study period. CONCLUSION:
These results suggest that BPE can be used as a nutraceutical or nutricosmetic
material for improving human skin hydration, gloss, and wrinkling.
PMID- 28421657
TI - Core outcome sets in women's and newborn health: a systematic review.
AB - BACKGROUND: Variation in outcome collection and reporting is a serious hindrance
to progress in our specialty; therefore, over 80 journals have come together to
support the development, dissemination, and implementation of core outcome sets.
OBJECTIVE: This study systematically reviewed and characterised registered,
progressing, or completed core outcome sets relevant to women's and newborn
health. SEARCH STRATEGY: Systematic search using the Core Outcome Measures in
Effectiveness Trial initiative and the Core Outcomes in Women's and Newborn
Health initiative databases. SELECTION CRITERIA: Registry entries, protocols,
systematic reviews, and core outcome sets. DATA COLLECTION AND ANALYSIS:
Descriptive statistics to describe characteristics and results. RESULTS: There
were 49 core outcome sets registered in maternal and newborn health, with the
majority registered in 2015 (n = 22; 48%) or 2016 (n = 16; 32%). Benign
gynaecology (n = 8; 16%) and newborn health (n = 3; 6%) are currently under
represented. Twenty-four (52%) core outcome sets were funded by international (n
= 1; <1%), national (n = 18; 38%), and regional (n = 4; 8%) bodies. Seven
protocols were published. Twenty systematic reviews have characterised the
inconsistency in outcome reporting across a broad range of relevant healthcare
conditions. Four core outcome sets were completed: reconstructive breast surgery
(11 outcomes), preterm birth (13 outcomes), epilepsy in pregnancy (29 outcomes),
and maternity care (48 outcomes). The quantitative, qualitative, and consensus
methods used to develop core outcome sets varied considerably. CONCLUSIONS: Core
outcome sets are currently being developed across women's and newborn health,
although coverage of topics is variable. Development of further infrastructure to
develop, disseminate, and implement core outcome sets is urgently required.
TWEETABLE ABSTRACT: Forty-nine women's and newborn core outcome sets registered.
50% funded. 7 protocols, 20 systematic reviews, and 4 core outcome sets
published. @coreoutcomes @jamesmnduffy.
PMID- 28421658
TI - Transcriptional signatures of connectomic subregions of the human striatum.
AB - Functionally distinct regions of the brain are thought to possess a
characteristic connectional fingerprint - a profile of incoming and outgoing
connections that defines the function of that area. This observation has
motivated efforts to subdivide brain areas using their connectivity patterns.
However, it remains unclear whether these connectomically-defined subregions can
be distinguished at the molecular level. Here, we combine high-resolution
diffusion-weighted magnetic resonance imaging with transcriptomic data to show
that connectomically-defined subregions of the striatum carry distinct
transcriptional signatures. Using data-driven clustering of diffusion
tractography, seeded from the striatum in 100 healthy individuals, we identify a
tripartite organization of the caudate and putamen that comprises ventral, dorsal
and caudal subregions. We then use microarray data of gene expression levels in
19 343 genes, taken from 98 tissue samples distributed throughout the striatum,
to accurately discriminate the three connectomically-defined subregions with 80
90% classification accuracy using linear support vector machines. This
classification accuracy was robust at the group and individual level and was
superior for our parcellation of the striatum when compared with parcellations
based on anatomical boundaries or other criteria. Genes contributing strongly to
classification were enriched for gene ontology categories including dopamine
signaling, glutamate secretion, response to amphetamine and metabolic pathways,
and were implicated in risk for disorders such as schizophrenia, autism and
Parkinson's disease. Our findings highlight a close link between regional
variations in transcriptional activity and inter-regional connectivity in the
brain, and suggest that there may be a strong genomic signature of
connectomically-defined subregions of the brain.
PMID- 28421659
TI - The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated
with autophagy induction through cAMP signaling.
AB - SCOPE: Although the previous trials of inflammation have indicated that morin
hydrate (MO) hold considerable promise, understanding the distinct mechanism of
MO against inflammation remains a challenge. METHODS AND RESULTS: This study
investigated the effect of MO in atherosclerosis in ApoE-/- mice and underlying
cell signaling of MO effect in inflammation in human umbilical vein endothelial
cells (HUVECs). Administration of MO significantly reduced serum lipid level,
inflammatory cytokines (TNF-alpha and ICAM-1), and atherosclerotic plaque
formation in vivo. MO presence attenuated the expression of TNF-alpha-induced
inflammatory cytokines (ICAM-1, COX-2, and MMP-9), and remarkably enhanced
microtubule associated protein 1 light chain 3 beta 2 (MAP1LC3B2) expression and
sequestosome 1 (SQSTM1/p62) degradation in HUVECs. These MO effects were
significantly prevented by the presence of autophagic inhibitors, 3-methyladenine
(3-MA), or chloroquine (CQ), as well as siRNA suppression of ATG5 and BECN1. MO
increased intracellular cAMP levels and activated cAMP-PKA-AMPK-SIRT1 signaling
in vivo and in vitro. These changes resulted in increased expression of autophagy
related protein MAP1LC3B2 and decreased secretion of inflammatory cytokines (ICAM
1, COX-2, and MMP-9). CONCLUSION: Our results suggest that anti-AS and anti
inflammatory effects of MO are largely associated with its induction of autophagy
through stimulation of cAMP-PKA-AMPK-SIRT1 signaling pathway.
PMID- 28421660
TI - Biocatalytic Asymmetric Phosphorylation Catalyzed by Recombinant Glycerate-2
Kinase.
AB - The efficient synthesis of pure d-glycerate-2-phosphate is of great interest due
to its importance as an enzyme substrate and metabolite. Therefore, we
investigated a straightforward one-step biocatalytic phosphorylation of glyceric
acid. Glycerate-2-kinase from Thermotoga maritima was expressed in Escherichia
coli, allowing easy purification. The selective glycerate-2-kinase-catalyzed
phosphorylation was followed by 31 P NMR and showed excellent enantioselectivity
towards phosphorylation of the d-enantiomer of glyceric acid. This
straightforward phosphorylation reaction and subsequent product isolation enabled
the preparation of enantiomerically pure d-glycerate 2-phosphate. This
phosphorylation reaction, using recombinant glycerate-2-kinase, yielded d
glycerate 2-phosphate in fewer reaction steps and with higher purity than
chemical routes.
PMID- 28421661
TI - Safety in psychiatric inpatient care: The impact of risk management culture on
mental health nursing practice.
AB - The discourse of safety has informed the care of individuals with mental illness
through institutionalization and into modern psychiatric nursing practices.
Confinement arose from safety: out of both societal stigma and fear for public
safety, as well as benevolently paternalistic aims to protect individuals from
self-harm. In this paper, we argue that within current psychiatric inpatient
environments, safety is maintained as the predominant value, and risk management
is the cornerstone of nursing care. Practices that accord with this value are
legitimized and perpetuated through the safety discourse, despite evidence
refuting their efficacy, and patient perspectives demonstrating harm. To
illustrate this growing concern in mental health nursing care, we provide four
exemplars of risk management strategies utilized in psychiatric inpatient
settings: close observations, seclusion, door locking and defensive nursing
practice. The use of these strategies demonstrates the necessity to shift
perspectives on safety and risk in nursing care. We suggest that to re-centre
meaningful support and treatment of clients, nurses should provide
individualized, flexible care that incorporates safety measures while also
fundamentally re-evaluating the risk management culture that gives rise to and
legitimizes harmful practices.
PMID- 28421662
TI - The outer membrane vesicles: Secretion system type zero.
AB - Gram-negative bacteria have mechanisms through which they can colonize and
survive in different environments, such as the secretion systems types (1-6) that
have been widely studied and characterized. Nowadays, some authors have proposed
extracellular structures, such as the outer membrane vesicles (OMVs), to be
considered as an additional and independent secretion system. The OMVs are
spherical particles of 50-250 nm in diameter; they originate in the outer
membrane, and therefore they have a very similar composition to the latter. These
particles can transport an important variety of biomolecules: enzymes, toxins,
antigenic determinants and even nucleic acids. Thus, it is of great interest to
collect data describing the advantages of the transport of biomolecules through
the OMVs and, thus, determine their role as a potential secretion system.
PMID- 28421664
TI - Intermediate-term and long-term outcome of piggyback drainage: connecting
glaucoma drainage device to a device in-situ for improved intraocular pressure
control.
AB - IMPORTANCE: This study provides results of a treatment option for patients with
failed primary glaucoma drainage device. BACKGROUND: The study aimed to describe
and evaluate the long-term intraocular pressure control and complications of a
new technique joining a second glaucoma drainage device directly to an existing
glaucoma drainage device termed 'piggyback drainage'. DESIGN: This is a
retrospective, interventional cohort study. PARTICIPANTS: Eighteen eyes of 17
patients who underwent piggyback drainage between 2004 and 2013 inclusive have
been studied. All patients had prior glaucoma drainage device with uncontrolled
intraocular pressure. METHODS: The piggyback technique involved suturing a
Baerveldt (250 or 350 mm) or Molteno3 glaucoma drainage device to an unused
scleral quadrant and connecting the silicone tube to the primary plate bleb. MAIN
OUTCOME MEASURES: Failure of intraocular pressure control defined as an
intraocular pressure greater than 21 mmHg on maximal therapy on two separate
occasions or further intervention to control intraocular pressure. RESULTS: The
intraocular pressure was controlled in seven eyes (39%) at last follow-up with a
mean follow-up time of 74.2 months. The mean preoperative intraocular pressure
was 27.1 mmHg (95% confidence interval 23.8-30.3) compared with 18.4 mmHg (95%
confidence interval 13.9-22.8) at last follow-up. The mean time to failure was
57.1 months (95% confidence interval 32.2-82), and the mean time to further
surgery was 72.3 months (95% confidence interval 49.9-94.7). Lower preoperative
intraocular pressure was associated with longer duration of intraocular pressure
control (P = 0.048). If the intraocular pressure was controlled over 2 years, it
continued to be controlled over the long term. Two eyes (11%) experienced corneal
decompensation. CONCLUSIONS: Piggyback drainage represents a viable surgical
alternative for the treatment of patients with severe glaucoma with failing
primary glaucoma drainage device, particularly in those at high risk of corneal
decompensation.
PMID- 28421663
TI - Cloning and plant-based production of antibody MC10E7 for a lateral flow
immunoassay to detect [4-arginine]microcystin in freshwater.
AB - Antibody MC10E7 is one of a small number of monoclonal antibodies that bind
specifically to [Arg4]-microcystins, and it can be used to survey natural water
sources and food samples for algal toxin contamination. However, the development
of sensitive immunoassays in different test formats, particularly user-friendly
tests for on-site analysis, requires a sensitive but also cost-effective
antibody. The original version of MC10E7 was derived from a murine hybridoma, but
we determined the sequence of the variable regions using the peptide mass
assisted cloning strategy and expressed a scFv (single-chain variable fragment)
format of this antibody in yeast and a chimeric full-size version in leaves of
Nicotiana tabacum and Nicotiana benthamiana to facilitate inexpensive and
scalable production. The specific antigen-binding activity of the purified
antibody was verified by surface plasmon resonance spectroscopy and ELISA,
confirming the same binding specificity as its hybridoma-derived counterpart. The
plant-derived antibody was used to design a lateral flow immunoassay (dipstick)
for the sensitive detection of [Arg4]-microcystins at concentrations of 100-300
ng/L in freshwater samples collected at different sites. Plant-based production
will likely reduce the cost of the antibody, currently the most expensive
component of the dipstick immunoassay, and will allow the development of further
antibody-based analytical devices and water purification adsorbents for the
efficient removal of toxic contaminants.
PMID- 28421665
TI - Evaluation of high-intensity focused ultrasound ablation for uterine fibroids: an
IDEAL prospective exploration study.
AB - OBJECTIVE: To evaluate the clinical outcomes of high-intensity focused ultrasound
(HIFU) and surgery in treating uterine fibroids, and prepare for a definitive
randomised trial. DESIGN: Prospective multicentre patient choice cohort study
(IDEAL Exploratory study) of HIFU, myomectomy or hysterectomy for treating
symptomatic uterine fibroids. SETTING: 20 Chinese hospitals. POPULATION OR
SAMPLE: 2411 Chinese women with symptomatic fibroids. METHODS: Prospective non
randomised cohort study with learning curve analysis (IDEAL Stage 2b Prospective
Exploration Study). MAIN OUTCOME MEASURES: Complications, hospital stay, return
to normal activities, and quality of life (measured with UFS-Qol and SF-36 at
baseline, 6 and 12 months), and need for further treatment. Quality-of-life
outcomes were adjusted using regression modelling. HIFU treatment quality was
evaluated using LC-CUSUM to identify operator learning curves. A health economic
analysis of costs was performed. RESULTS: 1353 women received HIFU, 472
hysterectomy and 586 myomectomy. HIFU patients were significantly younger (P <
0.001), slimmer (P < 0.001), better educated (P < 0.001), and wealthier (P =
0.002) than surgery patients. Both UFS and QoL improved more rapidly after HIFU
than after surgery (P = 0.002 and P = 0.001, respectively at 6 months), but
absolute differences were small. Major adverse events occurred in 3 (0.2%) of
HIFU and in 133 (12.6%) of surgical cases (P < 0.001). Median time for hospital
stay was 4 days (interquartile range, 0-5 days), 10 days (interquartile range, 8
12.5 days) and 8 days (interquartile range, 7-10 days). CONCLUSIONS: HIFU caused
substantially less morbidity than surgery, with similar longer-term QoL. Despite
group baseline differences and lack of blinding, these findings support the need
for a randomised controlled trial (RCT) of HIFU treatment for fibroids. The IDEAL
Exploratory design facilitated RCT protocol development. TWEETABLE ABSTRACT: HIFU
had much better short-term outcomes than surgery for fibroids in 2411-patient
Chinese IDEAL format study.
PMID- 28421666
TI - Genetic interplay between human longevity and metabolic pathways - a large-scale
eQTL study.
AB - Human longevity is a complex phenotype influenced by genetic and environmental
components. Unraveling the contribution of genetic vs. nongenetic factors to
longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing
based expression quantitative trait loci study (eQTL) with subsequent
heritability analysis. The investigation was performed on blood samples from 244
individuals from Germany and Denmark, representing various age groups including
long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed
for the first time that human longevity is associated with a depletion of
metabolic pathways in a genotype-dependent and independent manner. Further
analyses indicated that 20% of the differentially expressed genes are influenced
by genetic variants in cis. The subsequent study of twins showed that the
transcriptional activity of a third of the differentially regulated genes is
heritable. These findings suggest that longevity-associated biological processes
such as altered metabolism are, to a certain extent, also the driving force of
longevity rather than just a consequence of old age.
PMID- 28421668
TI - Effects of Stoichiometry on the H2 -Storage Properties of Mg(NH2 )2 -LiH-LiBH4
Tri-Component Systems.
AB - The hydrogen desorption pathways and storage properties of 2 Mg(NH2 )2 -3 LiH
xLiBH4 samples (x=0, 1, 2, and 4) were investigated systematically by a
combination of pressure composition isotherm (PCI), differential scanning
calorimetric (DSC), and volumetric release methods. Experimental results showed
that the desorption peak temperatures of 2 Mg(NH2 )2 -3 LiH-xLiBH4 samples were
approximately 10-15 degrees C lower than that of 2 Mg(NH2 )2 -3 LiH. The 2
Mg(NH2 )2 -3 LiH-4 LiBH4 composite in particular began to release hydrogen at 90
degrees C, thereby exhibiting superior dehydrogenation performance. All of the
LiBH4 -doped samples could be fully dehydrogenated and re-hydrogenated at a
temperature of 143 degrees C. The high hydrogen pressure region (above 50 bar)
of PCI curves for the LiBH4 -doped samples rose as the amount of LiBH4 increased.
LiBH4 changed the desorption pathway of the 2 Mg(NH2 )2 -3 LiH sample under a
hydrogen pressure of 50 bar, thereby resulting in the formation of MgNH and
molten [LiNH2 -2 LiBH4 ]. That is different from the dehydrogenation pathway of 2
Mg(NH2 )2 -3 LiH sample without LiBH4 , which formed Li2 Mg2 N3 H3 and LiNH2 , as
reported previously. In addition, the results of DSC analyses showed that the
doped samples exhibited two independent endothermic events, which might be
related to two different desorption pathways.
PMID- 28421667
TI - Serum levels of Wisteria floribunda agglutinin-positive Mac-2 binding protein
reflect the severity of chronic pancreatitis.
AB - OBJECTIVES: To evaluate the utility of serum Wisteria floribunda agglutinin
positive Mac-2 binding protein (WFA + -M2BP) level as a marker for chronic
pancreatitis (CP). METHODS: We measured the serum WFA+ -M2BP level of 74 patients
with CP who had undergone endoscopic retrograde cholangiopancreatography and 30
normal controls (NC) using a glycan sugar chain-based immunoassay and
investigated the relationship between serum WFA+ -M2BP levels and the Cambridge
classification of CP. RESULTS: Serum WFA+ -M2BP level was significantly higher in
patients with CP than in NC (0.64 +/- 0.28 vs 0.34 +/- 0.25, P < 0.001). The
levels (expressed as cut-off index) of WFA+ -M2BP for the classification of mild,
moderate and marked CP were 0.44, 0.63 and 0.87, respectively. Thus, serum WFA+
M2BP levels increased with increasing CP severity. With a cut-off value of 0.34,
0.59 and 0.61, the area under the receiver operating characteristic curve,
sensitivity and specificity were 0.829, 91.9% and 63.3% for mild CP; 0.891, 81.8%
and 85.0% for moderate CP; and 0.888, 92.0% and 74.7% for marked CP,
respectively. Multivariate analysis revealed that elevated serum WFA+ -M2BP was
independently associated with moderate and marked CP, respectively. CONCLUSION:
Serum WFA+ -M2BP level is a useful marker for grading CP severity.
PMID- 28421669
TI - Misfortune may be a blessing in disguise: Fairness perception and emotion
modulate decision making.
AB - Fairness perception and equality during social interactions frequently elicit
affective arousal and affect decision making. By integrating the dictator game
and a probabilistic gambling task, this study aimed to investigate the effects of
a negative experience induced by perceived unfairness on decision making using
behavioral, model fitting, and electrophysiological approaches. Participants were
randomly assigned to the neutral, harsh, or kind groups, which consisted of
various asset allocation scenarios to induce different levels of perceived
unfairness. The monetary gain was subsequently considered the initial asset in a
negatively rewarded, probabilistic gambling task in which the participants were
instructed to maintain as much asset as possible. Our behavioral results
indicated that the participants in the harsh group exhibited increased levels of
negative emotions but retained greater total game scores than the participants in
the other two groups. Parameter estimation of a reinforcement learning model
using a Bayesian approach indicated that these participants were more loss
aversive and consistent in decision making. Data from simultaneous ERP recordings
further demonstrated that these participants exhibited larger feedback-related
negativity to unexpected outcomes in the gambling task, which suggests enhanced
reward sensitivity and signaling of reward prediction error. Collectively, our
study suggests that a negative experience may be an advantage in the modulation
of reward-based decision making.
PMID- 28421670
TI - An epidemic of allergic contact dermatitis caused by a new allergen,
caprylhydroxamic acid, in moisturizers.
AB - BACKGROUND: In 2016, dermatologists in Finland suspected contact allergy in
several patients using moisturizers under the trade name Apobase(r). Following a
formulation change, PhenostatTM, which is a mixture of phenoxyethanol,
caprylhydroxamic acid, and methylpropanediol, was used as a preservative in
Apobase(r) moisturizers in Finland. OBJECTIVES: To confirm the suspected contact
allergy to Apobase(r) cream, oily cream, and/or lotion, and to identify the
specific contact allergen and define its optimal patch test concentration.
METHODS: Thirty-nine patients with suspected contact allergy to Apobase(r) creams
or lotion were patch tested in four Finnish dermatological clinics. The patch
tests included old and new Apobase(r) formulas and their preservative agents:
phenoxyethanol, methylpropanediol, and dilution series of PhenostatTM and
caprylhydroxamic acid or its potassium salt. RESULTS: The patch tests showed
positive reactions to the new Apobase(r) formulas, PhenostatTM, and
caprylhydroxamic acid or its potassium salt, but not to the old Apobase(r)
formulas, methylpropanediol, or phenoxyethanol. CONCLUSIONS: We found a new
contact allergen, caprylhydroxyamic acid, which caused an epidemic of allergic
contact dermatitis in patients using moisturizers containing this preservative.
Whether the sensitizing capacity of caprylhydroxamic acid depends on the other
chemicals used in Apobase(r) moisturizers needs further investigation.
PMID- 28421671
TI - Controlled Growth of CH3 NH3 PbI3 Using a Dynamically Dispensed Spin-Coating
Method: Improving Efficiency with a Reproducible PbI2 Blocking Layer.
AB - It is commonly believed that excess PbI2 has beneficial effects for perovskite
solar cells owing to the modification of charge-transport behavior at interfaces,
by surface passivation and by blocking electron-hole recombination. Here, we
introduce a dynamically dispensed spin-coating technique in a two-step deposition
to form a perovskite layer with controllable quantities of crystalline PbI2 .
Using this technique, the concentration of CH3 NH3 I solution is kept constant at
the reaction interface, ensuring smooth growth of films. By changing the spinning
rate during the reaction, the PbI2 conversion ratio and perovskite cuboid size
can be optimized, resulting in a power conversion efficiency improvement over
control devices. This dynamically dispensed technique represents a repeatable
method for compositional control in perovskite solar cells and improves our
understanding of how a PbI2 blocking layer improves the performance of perovskite
solar cells.
PMID- 28421672
TI - A Transplant-Specific Quality Initiative-Introducing TransQIP: A Joint Effort of
the ASTS and ACS.
AB - In an attempt to improve surgical quality in the field of transplantation, the
American College of Surgeons (ACS) and American Society of Transplant Surgeons
have initiated a national quality improvement program in transplantation. This
transplant-specific quality improvement program, called TransQIP, has been built
from the ground up by transplant surgeons and captures detailed information on
donor and recipient factors as well as transplant-specific outcomes. It is built
upon the existing ACS/National Surgical Quality Improvement Program
infrastructure and is designed to capture 100% of liver and kidney transplants
performed at participating sites. TransQIP has completed its alpha pilot and will
embark upon its beta phase at approximately 30 centers in the spring of 2017.
Going forward, we anticipate TransQIP will help satisfy Centers for Medicare and
Medicaid Services requirements for a quality improvement program, surgeon
requirements for maintenance of certification, and qualify as a clinical practice
improvement activity under the Merit-Based Incentive Payment System. Most
importantly, we believe TransQIP will provide insight into surgical outcomes in
transplantation that will allow the field to provide better care to our patients.
PMID- 28421674
TI - Retraction statement: Dynamic complex formation between HD-GYP, GGDEF and PilZ
domain proteins regulates motility in Xanthomonas campestris.
AB - : The following article from Molecular Microbiology (2012) 86(3), 557-567,
'Dynamic complex formation between HD-GYP, GGDEF and PilZ domain proteins
regulates motility in Xanthomonas campestris' by Robert P. Ryan, Yvonne McCarthy,
Patrick A. Kiely, Rosemary O'Connor, Chuck S. Farah, Judith P. Armitage and J.
Maxwell Dow published online in Wiley Online Library (wileyonlinelibrary.com),
has been retracted by agreement between the authors, the journal Editor-in-Chief,
John D Helmann, and John Wiley & Sons Ltd. Since publication of the above
article, it has been brought to our attention that there are several image
duplications across Figures 3, 5 and 6 including duplication with another article
in PNAS: 'Cell-cell signal-dependent dynamic interactions between HD-GYP and
GGDEF domain proteins mediate virulence in Xanthomonas campestris', by Robert P.
Ryan, Yvonne McCarthy, Maxuel Andrade, Chuck S. Farah, Judith P. Armitage, and J.
Maxwell Dow; PNAS (2010) 107(13), 5989-5994. The authors apologise for the errors
that arose due to poor labelling of the electronic images used in the
construction of the figures and for not spotting the duplication during review,
and, with agreement of all parties, the decision has been made to retract this
article. We apologise for any inconvenience the publication of this work may have
caused our readers. REFERENCES: Ryan, R.P., McCarthy, Y., Andrade, M., Farah,
C.S., Armitage, J.P., and Dow, J.M. (2010) Cell-cell signal-dependent dynamic
interactions between HD-GYP and GGDEF domain proteins mediate virulence in
Xanthomonas campestris. PNAS 107: 5989-5994. DOI: 10.1073/pnas.0912839107. Ryan,
R.P., McCarthy, Y., Kiely, P.A., O'connor, R., Farah, C.S., Armitage, J.P., and
Dow, J.M. (2012) Dynamic complex formation between HD-GYP, GGDEF and PilZ domain
proteins regulates motility in Xanthomonas campestris. Mol Microbiol 86: 557-567.
DOI: 10.1111/mmi.12000.
PMID- 28421673
TI - Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain
energy metabolism in mice.
AB - AIMS: The receptor tyrosine kinase ErbB4 is present throughout the primate brain
and has a distinct functional profile. In this study, we investigate the
potential role of endothelial ErbB4 receptor signaling in the brain. RESULTS:
Here, we show that the endothelial cell-specific deletion of ErbB4 induces
decreased exploratory behavior in adult mice. However, the water maze task for
spatial memory and the memory reconsolidation test reveal no changes;
additionally, we observe no impairment in CaMKII phosphorylation in
Cdh5Cre;ErbB4f/f mice, which indicates that the endothelial ErbB4 deficit leads
to decreased exploratory activity rather than direct memory deficits.
Furthermore, decreased brain metabolism, which was measured using micro-positron
emission tomography, is observed in the Cdh5Cre;ErbB4f/f mice. Consistently, the
immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1
(Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice.
Collectively, our findings suggest that endothelial ErbB4 plays a critical role
in regulating brain function, at least in part, through maintaining normal brain
energy homeostasis. CONCLUSIONS: Targeting ErbB4 or the modulation of endothelial
ErbB4 signaling may represent a rational pharmacological approach to treat
neurological disorders.
PMID- 28421675
TI - Proteomic composition of the acrostyle: Novel approaches to identify cuticular
proteins involved in virus-insect interactions.
AB - The acrostyle is a distinct anatomical region present on the cuticle at the inner
face of the common food/salivary canal at the tip of aphid maxillary stylets.
This conserved structure is of particular interest as it harbors the protein
receptors of at least 1 plant virus, Cauliflower mosaic virus, and presumably has
other roles in plant-insect interactions. Previously we reported immunolabeling
of a highly conserved motif of cuticular proteins from the CPR family (named for
the presence of a Rebers and Riddiford consensus) within the acrostyle. Here we
report the development of novel tools to further study the proteomic composition
of this region and to identify proteins involved in insect-virus interactions.
Using a series of antibodies against cuticular proteins from the RR-2 subfamily,
we identified additional peptides present within the acrostyle. Our results
demonstrated that the acrostyle is a complex structure containing multiple
domains of cuticular proteins accessible for interaction. In addition, an array
of overlapping peptides, which covers the diversity of the majority of the RR-2
subfamily, was developed as a generic tool to characterize cuticular
protein/pathogen interactions. Upon probing this array with Cucumber mosaic virus
particles, consensus peptide sequences from hybridizing peptides were identified.
Use of these novel tools has extended our knowledge of the proteomic composition
of insect maxillary stylets and identified sequences that could be involved in
virus binding, thus contributing to further elucidation of the various properties
and functions of the acrostyle.
PMID- 28421678
TI - Synergetic Effect of Chloride Doping and CH3 NH3 PbCl3 on CH3 NH3 PbI3-x Clx
Perovskite-Based Solar Cells.
AB - The chloride-doped CH3 NH3 PbI3-x Clx perovskite has attracted great attention
owing to clear performance enhancement by using a Cl additive and by the
controversial arguments on Cl function and the mechanism behind it. Herein, a
series of CH3 NH3 PbI3-x Clx perovskites with various Cl content was prepared
through a gas/solid reaction between CH3 NH2 gas and HPbI3-x Clx (x=0-1). The
small amount of Cl doping in CH3 NH3 PbI3-x Clx (x=0.05) could lead to band gap
broadening and significantly increase the perovskite grain size, and the phase
pure CH3 NH3 PbI2.95 Cl0.05 perovskites exhibited up to 17.44 % efficiency. For
Cl contents higher than 0.1 (x>0.1), CH3 NH3 PbCl3 formed and coexisted with CH3
NH3 PbI3-x Clx , and CH3 NH3 PbCl3 could help to improve the thermal stability of
CH3 NH3 PbI3-x Clx . However, the excessive co-existing wide-band-gap CH3 NH3
PbCl3 perovskites would inhibit the electron transfer and lead to a deterioration
of photovoltaic performance.
PMID- 28421677
TI - Mindfulness and its efficacy for psychological and biological responses in women
with breast cancer.
AB - Many breast cancer survivors have to deal with a variety of psychological and
physiological sequelae including impaired immune responses. The primary purpose
of this randomized controlled trial was to determine the efficacy of a
mindfulness-based stress reduction (MBSR) intervention for mood disorders in
women with breast cancer. Secondary outcomes were symptom experience, health
status, coping capacity, mindfulness, posttraumatic growth, and immune status.
This RTC assigned 166 women with breast cancer to one of three groups: MBSR (8
weekly group sessions of MBSR), active controls (self-instructing MBSR) and non
MBSR. The primary outcome measure was the Hospital Anxiety and Depression Scale.
Secondary outcome measures were: Memorial Symptom Assessment Scale, SF-36, Sense
of Coherence, Five Facets of Mindfulness Questionnaire, and Posttraumatic Growth
Index. Blood samples were analyzed using flow cytometry for NK-cell activity
(FANKIA) and lymphocyte phenotyping; concentrations of cytokines were determined
in sera using commercial high sensitivity IL-6 and IL-8 ELISA (enzyme-linked
immunosorbent assay) kits. Results provide evidence for beneficial effects of
MBSR on psychological and biological responses. Women in the MBSR group
experienced significant improvements in depression scores, with a mean pre-MBSR
HAD-score of 4.3 and post-MBSR score of 3.3 (P = 0.001), and compared to non-MBSR
(P = 0.015). Significant improvements on scores for distress, symptom burden, and
mental health were also observed. Furthermore, MBSR facilitated coping capacity
as well as mindfulness and posttraumatic growth. Significant benefits in immune
response within the MBSR group and between groups were observed. MBSR have
potential for alleviating depression, symptom experience, and for enhancing
coping capacity, mindfulness and posttraumatic growth, which may improve breast
cancer survivorship. MBSR also led to beneficial effect on immune function; the
clinical implications of this finding merit further research.
PMID- 28421679
TI - Thomas Starzl-Visionary and xenotransplantation pioneer: Commentary from the
International Xenotransplant Association Vanguard Committee.
PMID- 28421680
TI - Thomas E. Starzl, MD, PhD, 1926-2017.
PMID- 28421681
TI - Early clinical xenotransplantation experiences-An interview with Thomas E.
Starzl, MD, PhD.
AB - Dr Thomas E. Starzl, who died on March 4, 2017, was one of the great pioneers of
organ transplantation. He was also a pioneer in the field of xenotransplantation.
In 1964, he carried out baboon kidney transplants in six patients with terminal
renal disease for whom no living or deceased donor became available; graft
survival was for 19-60 days, the grafts being lost largely through continuous
complement activation. Between 1966 and 1974, he carried out one ex vivo liver
perfusion and three orthotopic liver transplants using chimpanzees as sources of
organs; graft survival was for <14 days. In 1992 and 1993, his team carried out
baboon liver transplantation in two patients with cirrhosis from hepatitis B
infection; graft survival was for 70 and 26 days, respectively. This early
clinical experience is briefly discussed. Toward the end of his life, Dr Starzl
was somewhat disillusioned by what he considered excessive regulation of medical
research in the United States and believed that new advances were now likely to
take place in countries such as China, where the regulatory framework is less
developed.
PMID- 28421682
TI - Predicting abstinence from methamphetamine use after residential rehabilitation:
Findings from the Methamphetamine Treatment Evaluation Study.
AB - INTRODUCTION AND AIMS: We previously found that residential rehabilitation
increased continuous abstinence from methamphetamine use 1 year after treatment.
We examine what client and treatment characteristics predict this outcome. DESIGN
AND METHODS: Participants (n = 176) were dependent on methamphetamine and
entering residential rehabilitation for methamphetamine use. Simultaneous
logistic regression was used to identify independent predictors of continuous
abstinence from methamphetamine use at 1 year follow-up. Measures included
demographics, drug use, psychiatric comorbidity (Diagnostic and Statistical
Manual of Mental Disorders, major depression, social phobia, panic disorder,
schizophrenia, mania and conduct disorder), symptoms of psychosis and hostility,
readiness to change, motivations for treatment and treatment characteristics
(duration, rapport, group and individual counselling). RESULTS: Participants
stayed in treatment for a median of 8 weeks; 23% remained abstinent at 1 year.
The only independent predictors of abstinence were more weeks in treatment
[adjusted odds ratio (AOR) 1.2, P < 0.001], better rapport with treatment
providers (AOR 2.4, P = 0.049) and receipt of individual counselling (AOR 3.7, P
= 0.013), whereas injecting methamphetamine predicted not achieving abstinence
(AOR = 0.25, P = 0.002). Individual counselling and good rapport increased
abstinence to 45%; for injectors, longer stays in treatment (13+ weeks) were
additionally needed to produce similar abstinence rates (43%). DISCUSSIONS AND
CONCLUSIONS: Abstinence from methamphetamine use following residential
rehabilitation could be significantly increased by providing individual
counselling, maintaining good rapport with clients and ensuring longer stays for
people who inject the drug. [McKetin R, Kothe A, Baker AL, Lee NK, Ross J, Lubman
DI. Predicting abstinence from methamphetamine use after residential
rehabilitation: Findings from the Methamphetamine Treatment Evaluation Study.
Drug Alcohol Rev 2018;37:70-78].
PMID- 28421683
TI - A numerical investigation on the effect of RF coil feed variability on global and
local electromagnetic field exposure in human body models at 64 MHz.
AB - PURPOSE: This study aims to investigate how the positions of the feeding sources
of the transmit radiofrequency (RF) coil, field orientation direction with
respect to the patient, and patient dimensions affect the global and local
electromagnetic exposure in human body models. METHODS: Three RF coil models were
implemented, namely a specific two-source (S2) feed and two multisource feed
configurations: generic 32-source (G32) and hybrid 16-source (H16). Thirty-two
feeding conditions were studied for the S2, whereas two were studied for the G32
and H16. The study was performed using five human body models. Additionally, for
two of the body models, the case of a partially implanted lead was evaluated.
RESULTS: The results showed an overall variation due to coil feeding conditions
of the whole-body specific absorption rate (SAR) of less than 20%, but deviations
up to 98% of the magnitude of the electric field tangential to a possible lead
path. For the analysis with the partially implanted lead, a variation of local
SAR at the tip of the lead of up to 60% was observed with respect to feed
position and field orientation direction. CONCLUSION: The results of this study
suggest that specific information about feed position and field orientation
direction must be considered for an accurate evaluation of patient exposure. Magn
Reson Med 79:1135-1144, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28421684
TI - Navigating the Rolling Hills of Justice: Mental Disabilities, Employment and the
Evolving Jurisprudence of the Americans with Disabilities Act.
AB - Mental illness and disability affect millions of individuals yearly in the U.S.
The most important legislation protecting the mentally disabled in the workplace
in the U.S. over the last half century has been the Americans with Disabilities
Act (ADA) and its associated legislation and guidance. Although the employee
should first request reasonable accommodation with the employer, evaluation by a
mental health professional is one of the initial steps for individuals who report
significant psychiatric symptoms that are impairing their functioning at work in
the U.S.. Important regulations and laws in the United States that are essential
knowledge to performing thorough mental disability evaluations include the ADA
and Americans with Disabilities Act Amendments Act of 2008 (ADAAA), Social
Security Disability, Workers' Compensation, and private disability insurance.
These laws differ in applicability and in their definitions of disability. Social
Security Disability is applicable to workers who have long-term impairments
regardless of whether the disability arose on or off the job, while Worker's
Compensation is specific to persons with work-related illness and injuries that
occur on the job (Reno, Williams, & Sengupta, ). The Social Security definition
of a disabled person is a person who is not "able to engage in any substantial
gainful activity because of a medically-determinable physical or mental
impairment(s): that is expected to result in death, or that has lasted or is
expected to last for a continuous period of at least 12 months" (Social Security
Red Book, ). However, the Workers' Compensation definition of what
illnesses/injuries are compensated, the level of benefits and who provides the
insurance are state-specific. Due to these differences in definition of
disability, it is essential for the mental health professional performing a
mental disability evaluation to clarify with the referral source or referring
agency which legislation and laws they feel are directly relevant to the specific
situation before starting the evaluation. While the ADA and ADA Amendments Act of
2008 have had the greatest impact on the improvement of conditions for mentally
disabled individuals in employment over the last 25 years, they have also been
the most challenging by far for mental health experts to understand and apply
(Cook, ). Interestingly, the ADA has had a much quicker effect on improving
access to services for the medically disabled as compared with the mentally
disabled in the U.S. (Ullman, Johnsen, Moss, & Burris, ). This article reviews
the history and status of current ADA- and ADAAA-related law and employment as
well as Canadian disability law and global progress towards universal disability
legislation as evidenced by the 2006 Convention on the Rights of Persons with
Disabilities. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421685
TI - The Reach and Limitation of the ADA and its Integration Mandate: Implications for
the Successful Reentry of Individuals with Mental Disabilities in a Correctional
Population.
AB - This article argues that the ADA and its integration mandate, informed by
international standards, should extend to incarcerated individuals with mental
disabilities who reenter society, as they are at highly elevated risk for
unnecessary segregation in institutions such as homeless shelters or hospitals or
through reincarceration. An understanding of the precise services needed to
prevent these strongly related but distinct variants of institutionalization
requires a robust and continuing research agenda. In discussing the breadth of
the ADA, we explore its history, interpretations of its application in a variety
of contexts with respect to vulnerable populations and integration, and
enforcement. We also turn to international approaches to integration mandates as
they apply to reentry. By interpreting the domestic and international principles
that create the context for integration we hope to have provided a resource for
future application of the ADA integration in the context of prisoner reentry.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421686
TI - International Perspectives on Mental Disability and the Law: Introduction to this
Issue.
PMID- 28421687
TI - Contemporary Data and Trends in the Economic Costs of Mental Disabilities.
AB - This article addresses the economic effects of mental disabilities by analyzing
contemporary data in the context of micro- and macroeconomic thought and relevant
statistical literature. Within the parameters of these conceptual and statistical
reference points, the authors seek to discern current trends in the direct,
indirect, and opportunity costs posed by mental disabilities, not only to the
individuals who suffer from them, but also to their families, to employers, and
to society as a whole. The authors also discuss uncertainties that inhere in
available data concerning both the prevalence of these conditions and the related
costs of treatment, as well as the complexity of drawing correlations among
variables with respect to these costs and the difficulty of identifying a
meaningful measure of the economic consequences that attend mental disabilities.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421688
TI - Typical medullary breast carcinoma: Clinical outcomes and treatment results.
PMID- 28421689
TI - On-resin N-formylation of peptides: a head-to-head comparison of reagents in
solid-phase synthesis of ligands for formyl peptide receptors.
AB - 4-Nitrophenyl formate was found to be the most convenient reagent in solid-phase
formylation of peptides with a high formylation degree within 20 min to 3 h
depending on reaction temperature and length of peptide.
PMID- 28421690
TI - Alcohol use of immigrant youths in The Netherlands: The roles of parents and
peers across different ethnic backgrounds.
AB - INTRODUCTION AND AIMS: The aims of this study were to examine the roles of
parental permissiveness toward alcohol use and affiliation with alcohol-using
peers in alcohol use in youths from various ethnic backgrounds, and whether the
role of peers was moderated by parental permissiveness. In addition, differences
in these associations between native Dutch and non-Western immigrant youths were
examined. DESIGN AND METHODS: Cross-sectional data of 578 youths with Surinamese,
Moroccan, Turkish, Antillean and Asian backgrounds and 81 native Dutch were used,
all aged 15-24. Alcohol use, affiliation with alcohol-using peers and parental
permissiveness were measured using self-report questionnaires. Regression models
controlled for age, religiousness, education level and parental alcohol use.
Because of very low levels of alcohol use, data from Turkish and Moroccan
immigrants were aggregated, and logistic regression analyses were performed.
RESULTS: Parental permissiveness and affiliation with alcohol-using peers were
positively related to level of alcohol use in youths with Surinamese, Antillean
and Asian backgrounds and played an equally strong role in native Dutch youths
with one exception. In Surinamese youths, parental permissiveness was more
strongly related to alcohol use than in native Dutch youths. In youths with a
Turkish/Moroccan background, parental permissiveness and affiliation with alcohol
using peers were strongly associated with any (versus no) alcohol use. Only
parental permissiveness was, equally strong, associated with any alcohol use in
native Dutch youths. DISCUSSION AND CONCLUSIONS: Irrespective of ethnic
background and differences in level of alcohol use, parental permissiveness and
affiliation with alcohol-using peers are related to youth alcohol use. [Creemers
HE, Spanakis P, Delforterie MJ, Huizink AC. Alcohol use of immigrant youths in
The Netherlands: The roles of parents and peers across different ethnic
backgrounds.
PMID- 28421691
TI - The impact of maternal employment on children's adiposity: Evidence from China's
labor policy reform.
AB - BACKGROUND: China has experienced a rapid growth in childhood adiposity in recent
years. Although a large number of studies examine the effect of maternal
employment on children's adiposity in developed countries, only a few studies
investigate the issue in developing countries. Moreover, existing studies tend to
suffer from a potential endogeneity issue. AIMS: We provide new evidence on the
causal effect of maternal employment on children's adiposity in China. MATERIALS
AND METHODS: We employ a difference-in-difference strategy that takes advantage
of China's 1995 legislative change to labor regulations, which reduced the number
of workdays from 6 to 5 days per week. Using longitudinal data from the China
Health and Nutrition Survey (CHNS), we compare children whose mothers are wage
earning employees to those whose mothers are self-employed because the reform
only affected the former. RESULTS: Although maternal employment and childhood
obesity in China exhibits the same positive association as in the United States,
our difference-in-difference estimates present a different picture. We find that
a reduction in the maternal labor supply led to children's weight gain. Further
investigation reveals that the effect was stronger among children who were male,
younger, in urban areas, and from households with low socioeconomic status.
DISCUSSION: Our evidence suggests that a change in maternal behaviors was likely
responsible for children's weight gain. In particular, a greater proportion of
treatment group mothers cooked and also devoted more time to cooking after the
reform, which led to an increased caloric intake by their children. Such weight
gain was beneficial for children who were previously underweight but harmful to
those who became overweight. CONCLUSION: The finding implies that additional
maternal time at home likely has a different effect in China compared to the
United States.
PMID- 28421695
TI - Evaluation of an interview skills training package for adolescents with speech,
language and communication needs.
AB - BACKGROUND & AIMS: We evaluated a structured intervention programme aimed at
preparing adolescents with developmental language disorders for job interviews.
Our primary outcome measures included change in ratings of verbal and non-verbal
social communication behaviours evident during mock interviews. METHODS &
PROCEDURES: In study 1, 12 participants, aged 17-19 years, from a specialist
sixth-form college completed the intervention and two mock interviews, one pre-
and one post-intervention. In study 2, 34 participants, aged 17-19 years,
completed a modified intervention programme and three mock interviews, one at
baseline (included to control for possible practise effects), one pre- and one
post-intervention. In both studies, interviews were video recorded and social
communication behaviours were coded by independent assessors blind to interview
time, participant diagnosis and therapy content. A repeated-measures design was
employed to measure change in communication behaviours. OUTCOMES & RESULTS: In
study 1, a significant increase in the number of 'positive' verbal and non-verbal
social communication behaviours was observed from pre- to post-intervention.
However, there was no significant change in the number of 'negative' behaviours
(i.e., fidgeting, irrelevant remarks). In study 2, there were no significant
changes in verbal behaviours, but significant group differences (though wide
individual variation) in both positive and negative non-verbal social
communication behaviours. CONCLUSIONS & IMPLICATIONS: Our findings suggest that
training specific social communication skills that are important for interview
success, and consistently reinforcing those behaviours during therapy practice,
can increase the use of those skills in an interview setting, though in this
heterogeneous population there was considerable variation in therapy outcome. The
skills of the interviewer were identified as a potential source of variation in
outcome, and a target for future research and practice.
PMID- 28421694
TI - Molecular engineering and plant expression of an immunoglobulin heavy chain
scaffold for delivery of a dengue vaccine candidate.
AB - In order to enhance vaccine uptake by the immune cells in vivo, molecular
engineering approach was employed to construct a polymeric immunoglobulin G
scaffold (PIGS) that incorporates multiple copies of an antigen and targets the
Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens
were tested in the context of dengue infection, for which there is currently no
globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII)
of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco
plants and Chinese Ovary Hamster cells. Purified mouse and human cEDIII-PIGS were
fractionated by HPLC into low and high molecular weight forms, corresponding to
monomers, dimers and polymers. cEDIII-PIGS were shown to retain important Fc
receptor functions associated with immunoglobulins, including binding to C1q
component of the complement and the low affinity Fcgamma receptor II, as well as
to macrophage cells in vitro. These molecules were shown to be immunogenic in
mice, with or without an adjuvant, inducing a high level IgG antibody response
which showed a neutralizing potential against the dengue virus serotype 2. The
cEDIII-PIGS also induced a significant cellular immune response, IFN-gamma
production and polyfunctional T cells in both the CD4+ and CD8+ compartments.
This proof-of-principle study shows that the potent antibody Fc-mediated cellular
functions can be harnessed to improve vaccine design, underscoring the potential
of this technology to induce and modulate a broad-ranging immune response.
PMID- 28421696
TI - Assessing causality in drug policy analyses: How useful are the Bradford Hill
criteria in analysing take-home naloxone programs?
AB - The Bradford Hill criteria for assessing causality are useful in assembling
evidence, including within complex policy analyses. In this paper, we argue that
the implementation of take-home naloxone (THN) programs in Australia and
elsewhere reflects sensible, evidence-based public health policy, despite the
absence of randomised controlled trials. However, we also acknowledge that the
debate around expanding access to THN would benefit from a careful consideration
of causal inference and health policy impact of THN program implementation. Given
the continued debate around expanding access to THN, and the relatively recent
access to new data from implementation studies, two research groups independently
conducted Bradford Hill analyses in order to carefully consider causal inference
and health policy impact. Hill's criteria offer a useful analytical tool for
interpreting current evidence on THN programs and making decisions about the
(un)certainty of THN program safety and effectiveness.
PMID- 28421698
TI - Historical harvests reduce neighboring old-growth basal area across a forest
landscape.
AB - While advances in remote sensing have made stand, landscape, and regional
assessments of the direct impacts of disturbance on forests quite common, the
edge influence of timber harvesting on the structure of neighboring unharvested
forests has not been examined extensively. In this study, we examine the impact
of historical timber harvests on basal area patterns of neighboring old-growth
forests to assess the magnitude and scale of harvest edge influence in a forest
landscape of western Oregon, USA. We used lidar data and forest plot measurements
to construct 30-m resolution live tree basal area maps in lower and middle
elevation mature and old-growth forests. We assessed how edge influence on total,
upper canopy, and lower canopy basal area varied across this forest landscape as
a function of harvest characteristics (i.e., harvest size and age) and
topographic conditions in the unharvested area. Upper canopy, lower canopy, and
total basal area increased with distance from harvest edge and elevation. Forests
within 75 m of harvest edges (20% of unharvested forests) had 4% to 6% less live
tree basal area compared with forest interiors. An interaction between distance
from harvest edge and elevation indicated that elevation altered edge influence
in this landscape. We observed a positive edge influence at low elevations (<800
m) and a negative edge influence at moderate to high elevations (>800 m).
Surprisingly, we found no or weak effects of harvest age (13-60 yr) and harvest
area (0.2-110 ha) on surrounding unharvested forest basal area, implying that
edge influence was relatively insensitive to the scale of disturbance and multi
decadal recovery processes. Our study indicates that the edge influence of past
clearcutting on the structure of neighboring uncut old-growth forests is
widespread and persistent. These indirect and diffuse legacies of historical
timber harvests complicate forest management decision-making in old-growth forest
landscapes by broadening the traditional view of stand boundaries. Furthermore,
the consequences of forest harvesting may reach across ownership boundaries,
highlighting complex governance issues surrounding landscape management of old
growth forests.
PMID- 28421699
TI - Hepatic infarction from portal vein thrombosis: A fatal consequence of acute
pancreatitis.
PMID- 28421697
TI - Endothelium originated from colorectal cancer stem cells constitute cancer blood
vessels.
AB - Tumor growth depends on the formation of blood vessels that provide the supply of
nutrients and oxygen. Previous data have shown that glioblastoma stem cells are
able to give rise to vascular cells to constitute the functional vessels in tumor
tissues. However, which kinds of vascular cells are generated from glioblastoma
stem cells is largely debated. In addition, there is little evidence showing that
the stem cells from other kinds of tumors can produce vascular cells to
constitute the functional blood vessels in tumor tissues. Here we show that
cancer stem cells of human colorectal carcinomas (CoCSC) can give rise to
vascular endothelial cells and compose the vasculatures in cancer tissues. The
human-cell-specific nuclear antigen NuMA+ vascular endothelial cells were
detected in the blood vessels in xenografts derived from CoCSC. NuMA+ endothelial
cells incorporated into functional blood vessels. Our data indicate that the
cancer stem cells derived from human colorectal carcinomas have the capacity to
generate functional blood vessels and provide a new mechanism for tumor
vasculogenesis in carcinoma.
PMID- 28421700
TI - Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.
AB - 22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features
including endocrine abnormalities. We aimed to characterize growth patterns,
hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS.
Anthropometric and laboratory measurements were obtained from the charts of 48
individuals (males=28, 8.0+/-6.8 visits/participant) followed at a national
22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3+/-4.9 years and
age at last evaluation 11.2+/-7.2 years. Median height-SDS was negative at all
ages. Height-SDS at last visit was correlated to the midparental height-SDS
(r=0.52 P=0.002). Yet, participants did not reach their target height, with a
difference of 1.06+/-1.07 SD (P <0.0001). Height-SDS at last visit of
participants with a heart defect was lower compared to participants with a normal
heart (-1.5+/-1.4 vs. -0.6+/-0.8, P=0.036), with lower height-SDS in the subgroup
of participants with severe heart defects (-2.1+/-1.6, P=0.009). Mean IGF1-SDS
was low (-0.99+/-1.68) but was not correlated with height-SDS. Thirteen patients
(27%) had hypoparathyroidism: 10 presented during infancy and 3 during
adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In
conclusions, individuals with 22q11.2 DS have a distinct growth pattern
consisting of growth restriction at all ages, resulting in final adult height in
the low-normal range. Hypoparathyroidism is common and may present during the
neonatal period as well as later in life. Thyroid abnormalities may present
during childhood, adolescence, or adulthood.
PMID- 28421701
TI - Corrigendum to "Having a son or daughter with Down syndrome: Perspectives from
mothers and fathers. Am J Med Genet Part A 155:2335-2347."
PMID- 28421702
TI - De Novo Variants Associated With Developmental Disability: Exome sequencing data
findings implicate new genes as potential sources of de novo mutations.
PMID- 28421703
TI - Foremost Prenatal Physician, Scientist Tapped to Lead National Child Health
Agency: Diana Bianchi, MD, is focused on fostering more genomics research,
enabling greater data-sharing collaboration among agencies in new role at NICHD.
PMID- 28421706
TI - Generative Topographic Mapping of Conformational Space.
AB - Herein, Generative Topographic Mapping (GTM) was challenged to produce planar
projections of the high-dimensional conformational space of complex molecules
(the 1LE1 peptide). GTM is a probability-based mapping strategy, and its capacity
to support property prediction models serves to objectively assess map quality
(in terms of regression statistics). The properties to predict were total, non
bonded and contact energies, surface area and fingerprint darkness. Map building
and selection was controlled by a previously introduced evolutionary strategy
allowed to choose the best-suited conformational descriptors, options including
classical terms and novel atom-centric autocorrellograms. The latter condensate
interatomic distance patterns into descriptors of rather low dimensionality, yet
precise enough to differentiate between close favorable contacts and atom
clashes. A subset of 20 K conformers of the 1LE1 peptide, randomly selected from
a pool of 2 M geometries (generated by the S4MPLE tool) was employed for map
building and cross-validation of property regression models. The GTM build-up
challenge reached robust three-fold cross-validated determination coefficients of
Q2 =0.7...0.8, for all modeled properties. Mapping of the full 2 M conformer set
produced intuitive and information-rich property landscapes. Functional and
folding subspaces appear as well-separated zones, even though RMSD with respect
to the PDB structure was never used as a selection criterion of the maps.
PMID- 28421707
TI - Content analysis of the professional journal of the Royal College of Speech and
Language Therapists, III: 1966-2015-into the 21st century.
AB - BACKGROUND: Following content analyses of the first 30 years of the UK speech and
language therapy professional body's journal, this study was conducted to survey
the published work of the speech (and language) therapy profession over the last
50 years and trace key changes and themes. AIM: To understand better the
development of the UK speech and language therapy profession over the last 50
years. METHODS & PROCEDURES: All volumes of the professional journal of the Royal
College of Speech and Language Therapists published between 1966 and 2015
(British Journal of Communication Disorders, European Journal of Communication
Disorders and International Journal of Language and Communication Disorders) were
examined using content analysis. The content was compared with that of the same
journal as it appeared from 1935 to 1965. OUTCOMES & RESULTS: The journal has
shown a trend towards more multi-authored and international papers, and a
formalization of research methodologies. The volume of papers has increased
considerably. Topic areas have expanded, but retain many of the areas of study
found in earlier issues of the journal. CONCLUSIONS & IMPLICATIONS: The journal
and its articles reflect the growing complexity of conditions being researched by
speech and language therapists and their professional colleagues and give an
indication of the developing evidence base for intervention and the diverse
routes which speech and language therapy practice has taken over the last 50
years.
PMID- 28421708
TI - Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross
Coupling.
AB - Vicinal stereocenters are found in many natural and unnatural compounds. Although
metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are
emerging as a powerful tool in organic synthesis, there have been virtually no
reports of processes that generate, much less control, vicinal stereocenters. In
this investigation, we establish that a chiral nickel catalyst can mediate doubly
stereoconvergent alkyl-alkyl cross-coupling, specifically, reactions of a racemic
pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of
stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.
PMID- 28421709
TI - Gene-environment interaction influences attachment-like style in mice.
AB - Attachment styles are established soon after birth and form the basis for a
healthy psychological life during adulthood. Here, we investigated whether
genetic background (i.e. isogenic strains: C57BL/6N and BALB/c) and parent-of
origin (i.e. reciprocal hybrids) epigenetic effects influence attachment-like
styles in mice. We discovered that a specific genetic and epigenetic assortment
exerts a role on the development of a secure or insecure attachment-like style.
In particular, when biological mothers raise their pups, the attachment-like
style is mainly secure, independently of the genetic background. However, when
foster mothers raise pups, the attachment-like style can be either secure or
insecure, depending on the particular genetic background, and this effect is
paternally transmitted. Finally, we observed that secure attachment-like in mice
leads to greater sociability during adulthood, while insecure attachment-like
leads to reduced sociability. Our study sheds light on gene-environment
interactions that shape the attachment-like style early in development and pave
the way for a healthy psychological life.
PMID- 28421710
TI - Synovial sarcoma metastatic to the parotid gland: A possible pitfall in salivary
gland fine needle aspiration cytology. Report of a case with immunocytochemical
and fluorescence in situ hybridization findings.
AB - We report one case of metastatic synovial sarcoma (SS) to the parotid gland in a
93-year-old male. The patient had undergone upper left pulmonary lobectomy with
mediastinal lymphadenectomy for SS of the lung 5 years before. The cytopathologic
presentation and the immunocytochemical findings on the FNA sample were
suggestive of a spindle cell myoepithelioma, while a SYT rearrangement was
identified by a FISH performed on a cytological smear of the lesion. The
diagnosis was further confirmed also by positive immunocytochemical expression of
TLE1 on a section from the obtained cell block. The cytologic and
immunophenotypic findings are shortly discussed in view of the reported
immunophenotypic inconsistency of SS and of its differential diagnosis with
spindle cell myoepithelioma of the salivary glands.The importance of the recently
described TLE1 staining and its close correlation to SYT rearrangement is briefly
discussed.
PMID- 28421712
TI - Gastric cancer with pituitary metastasis presenting as symptomatic secondary
adrenal insufficiency: A case report.
PMID- 28421711
TI - Vitamin D status of White pregnant women and infants at birth and 4 months in
North West England: A cohort study.
AB - The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and
their infants has not been investigated at northern latitudes in a developed
county. A 2-year observational cohort study was undertaken in the North West of
England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants
during pregnancy and 4 months postdelivery and to explore factors associated with
these levels. Nutritional and lifestyle questionnaires were completed and 25OHD
levels measured at 28 weeks and 4 months postdelivery. Twenty-seven percent and
7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48%
and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have
significantly lower 25OHD than other skin types after controlling for time spent
outside and vitamin D intake. Twenty-four percent and 13% of infants had
insufficient and deficient 25OHD levels at 4 months. Unsupplemented breast-fed
infants have the highest level of insufficiency (67%) compared with formula-fed
infants (2%). Factors associated with infant serum 25OHD levels at 4 months
included breast feeding, supplementation, and time outside. WSW have a high
prevalence of insufficiency and deficiency during pregnancy which doubles 4
months after birth. Breast-fed infants of WSW are rarely considered at risk of
vitamin D insufficiency but have high rates compared with formula-fed infants.
This is the first study to show the finding that FST I WSW have significantly
lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and
time outside 14 (95%CI 7-21) nmol/L).
PMID- 28421713
TI - Identification, isolation, and synthesis of seven novel impurities of anti
diabetic drug Repaglinide.
AB - Seven unknown impurities in Repaglinide bulk drug batches at below 0.1% (ranging
from 0.05 to 0.10%) were detected by an ultra-performance liquid chromatographic
(UPLC) method. These impurities were isolated from the crude sample of
Repaglinide using preparative high performance liquid chromatography (prep-HPLC).
Based on liquid chromatography-electrospray ionization-mass spectrometry (LC
ESI/MS) study, the chemical structures of seven new impurities (8, 9, 10, 11, 13,
14, and 16) were presumed and characterized as 4-(cyanomethyl)-2-ethoxybenzoic
acid (8), 4-(cyanomethyl)-2-ethoxy-N-(3-methyl-1-(2-(piperidin-1
yl)phenyl)butyl)benzamide (9), 4-(2-amino-2-oxoethyl)-2-ethoxy-N-(3-methyl-1-(2
(piperidin-1-yl)phenyl)butyl) benzamide (10) and 2-(3-ethoxy-4-((3-methyl-1-(2
(piperidin-1-yl)phenyl)butyl) carbamoyl) phenyl) acetic acid (11) and 4
(cyanomethyl)-N-cyclohexyl-2-ethoxybenzamide (13), 2-(4-(cyclohexylcarbamoyl)-3
ethoxyphenyl) acetic acid (14) and N-cyclohexyl-4-(2-(cyclohexylamino)-2
oxoethyl)-2-ethoxybenzamide (16). The complete spectral analysis, proton nuclear
magnetic resonance (1 H NMR), 13 C NMR, MS, and infrared (IR) confirmed the
proposed chemical structures of impurities. Identification, structural
characterization, formation, and their synthesis was first reported in this
study. The impurity 11 was crystallized and structure was solved by single
crystal X-ray diffraction. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421714
TI - Endometrial cells on Pap tests: ideal reporting is more complex than just finding
the right age.
AB - BACKGROUND: The age for reporting normal endometrial cells (EMCs) on Pap tests
was changed to >= 45 years in the latest Bethesda update (2014). This
recommendation is solely based on age with no consensus on optimal reporting
guidelines. METHODS: Pap tests with EMCs for women >=40 years were retrieved from
our Laboratory Information System (LIS). Patient age, last menstrual period (LMP)
and available follow-up histology were recorded. Follow-up diagnoses were
categorized as: no significant pathology, benign, hyperplasia +/- atypia, or
malignant. The Fisher's exact test was used to assess the association between
categorical variables, p < .05 (two-sided test) was considered significant.
RESULTS: Of the 352 cases with EMCs, 155 had surgical follow-up. They showed no
malignancy in the 89 women between 40-49 years, compared with five malignancies
in the 66 women 50+ years (p = .016). The number of cases with significant
pathology (hyperplasia and malignant) was 4 (40-49 years) vs. 11 (50+ years) (p =
0.029). The LMP was inconsistently provided (57%) and women identified as
postmenopausal on requisition comprised all the malignancies and half the
hyperplasias. CONCLUSION: Combined effort by pathologists and clinicians
necessitates determining the best standardized clinicopathologic guidelines to
report EMCs and appropriate follow-up. Increasing the required age to >=50 years
would provide more optimal patient management; however, there are other
considerations beyond age. Reporting EMCs in postmenopausal women is a reasonable
alternative requiring consistent and accurate recording of LMP. Improving
provided information for pathologists, determining reporting requirements for
EMCs and standardizing clinical follow-up should be a multidisciplinary effort.
Diagn. Cytopathol. 2017;45:587-591. (c) 2017 Wiley Periodicals, Inc.
PMID- 28421715
TI - Effect of water bath temperature on physiological parameters and subjective
sensation in older people.
AB - AIM: In Japan, the incidence of water bathing-related cardiopulmonary accidents
among older people is high in winter. The purpose of the present study was to
investigate alterations in physiological characteristics and subjective thermal
sensations of older people when bathing in a cool environment. METHODS: We
assessed the skin temperature, rectal temperature, blood pressure, pulse rate,
body fluid loss (sweat and urine), and subjective thermal responses of 11 older
healthy male and 10 young male volunteers throughout 42 degrees C and 39 degrees
C bathing in a room at 20 degrees C with 50% humidity. RESULTS: At 42 degrees C
bathing, the rectal temperature during bathing and in the post-bathing period
were significantly lower in the older men than in the young men, and skin
temperature during the post-bathing period decreased gradually in the older men.
Systolic blood pressure and pulse rate immediately increased just after entering
42 degrees C water and decreased during bathing in the older men. With the
activities of dressing, systolic blood pressure increased followed by a decrease
during the post-bathing period. Thus, double product (pulse rate * systolic blood
pressure) increased during the bathing period. Although there was no significant
difference in body fluid loss between the older and younger men in 42 degrees C
water, the older men produced significantly less sweat. The older men also
reported feeling less warm after 42 degrees C bathing, and feeling less cold
during the post-bathing period after 39 degrees C bathing. CONCLUSIONS: These
results suggest that hot water bathing during cold seasons might induce more
serious physiological changes in older people. Geriatr Gerontol Int 2017; 17:
2164-2170.
PMID- 28421716
TI - Identification of a new HLA-DQB1*06 allele, HLA-DQB1*06:210, by monoallelic
Sanger sequencing.
AB - Sequence of the novel allele, HLA-DQB1*06:210, differs from HLA-DQB1*06:03:01 by
1 nucleotide exchange in exon 2.
PMID- 28421717
TI - Cognitive profiles in euthymic patients with bipolar disorders: results from the
FACE-BD cohort.
AB - OBJECTIVES: Although cognitive deficits are a well-established feature of bipolar
disorders (BD), even during periods of euthymia, little is known about cognitive
phenotype heterogeneity among patients with BD. METHODS: We investigated
neuropsychological performance in 258 euthymic patients with BD recruited via the
French network of expert centers for BD. We used a test battery assessing six
domains of cognition. Hierarchical cluster analysis of the cross-sectional data
was used to determine the optimal number of subgroups and to assign each patient
to a specific cognitive cluster. Subsequently, subjects from each cluster were
compared on demographic, clinical functioning, and pharmacological variables.
RESULTS: A four-cluster solution was identified. The global cognitive performance
was above normal in one cluster and below normal in another. The other two
clusters had a near-normal cognitive performance, with above and below average
verbal memory, respectively. Among the four clusters, significant differences
were observed in estimated intelligence quotient and social functioning, which
were lower for the low cognitive performers compared to the high cognitive
performers. CONCLUSIONS: These results confirm the existence of several distinct
cognitive profiles in BD. Identification of these profiles may help to develop
profile-specific cognitive remediation programs, which might improve functioning
in BD.
PMID- 28421719
TI - Therapeutic value of renal denervation in cardiovascular disease?
PMID- 28421718
TI - Small serine recombination systems ParA-MRS and CinH-RS2 perform precise excision
of plastid DNA.
AB - Selectable marker genes (SMGs) are necessary for selection of transgenic plants.
However, once stable transformants have been identified, the marker gene is no
longer needed. In this study, we demonstrate the use of the small serine
recombination systems, ParA-MRS and CinH-RS2, to precisely excise a marker gene
from the plastid genome of tobacco. Transplastomic plants transformed with the
pTCH-MRS and pTCH-RS2 vectors, containing the visual reporter gene DsRed flanked
by directly oriented MRS and RS2 recognition sites, respectively, were crossed
with nuclear-genome transformed tobacco plants expressing plastid-targeted ParA
and CinH recombinases, respectively. One hundred per cent of both types of F1
hybrids exhibited excision of the DsRed marker gene. PCR and Southern blot
analyses of DNA from F2 plants showed that approximately 30% (CinH-RS2) or 40%
(ParA-MRS) had lost the recombinase genes by segregation. The postexcision
transformed plastid genomes were stable and the excision events heritable. The
ParA-MRS and CinH-RS2 recombination systems will be useful tools for site
specific manipulation of the plastid genome and for generating marker-free
plants, an essential step for reuse of SMG and for addressing concerns about the
presence of antibiotic resistance genes in transgenic plants.
PMID- 28421720
TI - Enantioselective Organocatalytic Synthesis of a Secoyohimbane-Inspired Compound
Collection with Neuritogenic Activity.
AB - Natural products provide evolutionary validated core structures to inspire the
synthesis of new compound collections endowed with neurite growth-promoting
activity. Rhynchophylline is the major component of Uncaria species, and has been
used to treat neurological diseases in Chinese traditional medicine. Based on the
structure of this spirocyclic secoyohimbane alkaloid, we developed a highly
enantioselective and efficient organocatalyzed synthesis method to provide a
tetracyclic secoyohimbane scaffold incorporating a quaternary and three tertiary
stereogenic centers, in a one-pot multistep reaction sequence. A compound
collection of derived secoyohimbanes was synthesized and expanded by decorating
the periphery of the basic scaffold with additional substituents to increase the
diversity. Evaluation of the different subcollections of secoyohimbanes for
modulation of neurite outgrowth in the SH-SY5Y human cell line led to the
discovery of new compounds that promote neurite outgrowth.
PMID- 28421721
TI - FNAC aided diagnosis of clear cell sarcoma of kidney: Report of two cases in
infants.
AB - Clear cell sarcoma of kidney (CCSK) is a rare aggressive malignant renal neoplasm
with a high metastatic potential. Its outcome has however, improved with the
advent of doxorubicin based neoadjuvant chemotherapy. Here, we present two cases
of CCSK in infants diagnosed on cytology followed by nephrectomy. The first case
presented in the neonatal period and had the unusual histological finding of
islands of cartilage. The second case presented at the age of eight months. The
possibility of CCSK should, therefore, be considered in the differential
diagnoses of renal masses in infants as well as neonates. Diagn. Cytopathol.
2017;45:761-765. (c) 2017 Wiley Periodicals, Inc.
PMID- 28421722
TI - Second Primary Cancer Risk among Kidney Cancer Patients in Korea: A Population
Based Cohort Study.
AB - PURPOSE: Secondary primary cancers (SPCs) commonly arise in patients with renal
cell carcinoma (RCC). We designed the present study to estimate the SPC incidence
in Korean patients with RCC. MATERIALS AND METHODS: The study cohort was
population-based and consisted of 40,347 individuals from the Korean Central
Cancer Registry who were diagnosed with primary renal cancer between 1993 and
2013. Standardized incidence ratios (SIRs) for SPCs were estimated for different
ages at diagnosis, latencies, diagnostic periods, and treatments. RESULTS: For
patients with primary RCC, the risk of developing a SPC was higher than the risk
of developing cancer in the general population (SIR, 1.13; 95% confidence
interval, 1.08 to 1.18). Most cancer types showed higher incidences in patients
with RCC than in the general population. However, the relative incidence of
gastric cancer as an SPC varied by age. Gastric cancer incidence was elevated in
young patients (< 30 years) with RCC, but reduced in older (>= 30) patients with
RCC. Patients with advanced RCC died prematurely, regardless of SPC development.
In contrast, those with early-stage RCC survived for longer periods, although SPC
development affected their post-RCC survival. After SPC development, women had
better survival than men. CONCLUSION: In Korean patients with primary RCC, the
incidence of SPC was 13% higher than the incidence of cancer in the general
population. These findings may play important roles in the conduct of follow-up
evaluations and education for patients with RCC.
PMID- 28421723
TI - Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single
Institute in Korea.
AB - PURPOSE: This study retrospectively evaluated the clinical outcomes and
complications of proton beam therapy (PBT) in a single institution in Korea and
quantitatively analyzed the change in tumor volume after PBT using magnetic
resonance imaging (MRI). MATERIALS AND METHODS: Twenty-four treatment-naive
patients who underwent PBT for choroidal melanoma between 2009 and 2015 were
reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions.
Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and
annually thereafter. The tumor volume was reconstructed and evaluated by stacking
the tumor boundary in each thin-sliced axial T1-weighted image using MIM
software. RESULTS: The median follow-up duration was 36.5 months (range, 9 to 82
months). One patient had suspicious local progression and two patients had
distant metastasis. The 3-year local progression-free survival, distant
metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and
100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03
grade 3-4 toxicities were observed in four patients (16.7%), including one with
neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565+/-0.084
mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12
months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively.
CONCLUSION: The local controlrate and complication profile after PBT in
patientswith choroidal melanoma in Korea were comparable with those reported in a
previous PBT series. The change in tumor volume after PBT exhibited a gradual
regression pattern on MRI.
PMID- 28421724
TI - A National Study of Survival Trends and Conditional Survival in Nasopharyngeal
Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology
and End Results Registry.
AB - PURPOSE: Conditional survival (CS) provides important information on survival for
a period of time after diagnosis. Currently, information on CS patterns of
patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze
survival rate over time and estimate CS for NPC patients using a national
population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC
between 1973 and 2007 with at least 5-year follow-up were identified from the
Surveillance Epidemiology End Results registry. Traditional survival rates and
crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted
survival curves were plotted from the proportional hazards model using the
correct group prognosis method. RESULTS: registry. Traditional survival rates and
crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted
survival curves were plotted from the proportional hazards model using the
correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted
baseline 5-year overall survival improved significantly from 36.0% in patients
diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000
2007 (p < 0.01). CS analysis demonstrated that for every additional year
survived, adjusted probability of surviving the next 5 years increased from 66.7%
(localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to
83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had
survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology,
ethnicity, and stage subgroups initially, but converged with time. CONCLUSION:
Treatment outcomes of NPC patients have greatly improved over the decades.
Increases in CS become more prominent in patients with distant disease than in
those with localized or regional disease as patients survive longer. CS provides
more dynamic prognostic information for patients who have survived a period of
time after diagnosis.
PMID- 28421725
TI - No Association of Positive Superficial and/or Deep Margins with Local Recurrence
in Invasive Breast Cancer Treated with Breast-Conserving Surgery.
AB - PURPOSE: We evaluated the effect of positive superficial and/or deep margin
status on local recurrence (LR) in invasive breast cancer treated with breast
conserving surgery (BCS) followed by radiotherapy. MATERIALS AND METHODS: In
total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS
followed by radiotherapy from January 2000 to December 2008 were included in this
study. These patients were divided into three groups according to margin status:
clear resection margin status for all sections (group 1, n=3,195); positive
margin status in superficial and/or deep sections (group 2, n=121); and positive
peripheral parenchymal margin regardless of superficial and/or deep margin
involvement (group 3, n=87). The LR-free survival between these three groups was
compared and the prognostic role of margin status was analyzed. RESULTS: Across
all groups, age, tumor size, nodal status, and human epidermal growth factor
receptor 2 status did not significantly differ. High grade, positive extensive
intraductal component, hormone receptor positivity, hormone therapy received, and
chemotherapy not received were more prevalent in groups 2 and 3 than in group 1.
Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively.
Multivariate analysis revealed that group 3 was a significant predictor for LR
(hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep
margin was not (HR, 0.66; p=0.57). CONCLUSION: Superficial and/or deep margin
involvement following BCS is not an important predictor for LR.
PMID- 28421727
TI - The epidemic spreading of basal cell carcinoma: incidence trend, demographic
features, characteristics and risk factors in a retrospective study of 8557
lesions in Bologna.
AB - BACKGROUND: Basal cell carcinoma (BCC) has a rising incidence worldwide. The aim
was to evaluate incidence trend, demographic features and risk factors for BCC in
the area of Bologna in northern-central Italy. METHODS: All the consecutive
histopathologically diagnosed BCCs at the Dermatology of the Bologna University
from 1990 to 2014 were retrospectively reviewed. We evaluated the absolute number
of BCCs, the demographic features of patients and the characteristics of BCCs
with statistically significant correlations. RESULTS: During the investigated 25
years, 8,557 BCCs were collected in 7,297 patients. We observed that the
incidence of this cancer, after stabilizing around a plateau of 400 cases/year in
2005, progressively increased onwards reaching a maximum of cases (821) in 2014
(+105.25%), with a 8.32% mean increase per year in those last 9 years. Moreover,
we found a significant correlation (p<0.01%) between gender and the onset of BCC,
between the anatomic location and the occurrence of the tumor, between the onset
of recurrent or new BCCs and sun exposure. CONCLUSIONS: The present study
collects the largest series in the Italian literature focused on demographic
features and characteristics of BCC, highlights its higher increasing incidence
in Bologna and the need to improve preventive strategies to stem the epidemic
diagnosis of BCC.
PMID- 28421726
TI - Selection Criteria for Active Surveillance of Patients with Prostate Cancer in
Korea: A Multicenter Analysis of Pathology after Radical Prostatectomy.
AB - PURPOSE: Korean patients with prostate cancer (PC) typically present with a more
aggressive disease than patients in Western populations. Consequently, it is
unclear if the current criteria for active surveillance (AS) can safely be
applied to Korean patients. Therefore, this study was conducted to define
appropriate selection criteria for AS for patients with PC in Korea. MATERIALS
AND METHODS: We conducted a multicenter retrospective study of 2,126 patients
with low risk PC who actually underwent radical prostatectomy. The primary
outcome was an unfavorable disease, which was defined by non-organ confined
disease or an upgrading of the Gleason score to >= 7 (4+3). Predictive variables
of an unfavorable outcome were identified by multivariate analysis using randomly
selected training samples (n=1,623, 76.3%). We compared our selected criteria to
various Western criteria for the primary outcome and validated our criteria using
the remaining validation sample (n=503, 23.7%). RESULTS: A non-organ confined
disease rate of 14.9% was identified, with an increase in Gleason score >= 7
(4+3) of 8.7% and a final unfavorable disease status of 20.8%. The following
criteria were selected: Gleason score <= 6, clinical stage T1-T2a, prostate
specific antigen (PSA) <= 10 ng/mL, PSA density < 0.15 ng/mL/mL, number of
positive cores <= 2, and maximum cancer involvement in any one core <= 20%. These
criteria provided the lowest unfavorable disease rate (11.7%) when compared to
Western criteria (13.3%-20.7%), and their validity was confirmed using the
validation sample (5.9%). CONCLUSION: We developed AS criteria which are
appropriate for Korean patients with PC. Prospective studies using these criteria
are now warranted.
PMID- 28421728
TI - Oral pigmentation in physiologic conditions, post-inflammatory affections and
systemic diseases.
AB - Melanocytes are found throughout the oral mucosa but usually go unnoticed because
of their relatively low level of pigment production. When focally or generally
active in pigment production or proliferation they may be responsible for several
affections in the oral mucosae ranging from physiologic pigmentation, systemic
diseases to malignant neoplasms. The diagnosis of oral pigmentations (OP) is
usually challenging for the physician, but a careful examination of the oral
cavity may reveal the first manifestation of underlying systemic diseases.
Therefore, a full medical history (including drug assumption and smoking)
together with a general dermatological examination are mandatory and represent
the first approach to OPs. When the diagnosis cannot be reached clinically with
enough certainty, a biopsy for histological examination is needed, also in order
to exclude possible life threatening conditions such as melanoma. Dermoscopy is
another reliable diagnostic tool to make a differential diagnosis between
melanocytic lesions and other conditions and then to manage the follow-up of
patients. Few papers on the subject have been published in the dermatological
literature and the oral cavity is often poorly investigated during routine
dermatological examinations. We therefore decided to perform a review of benign
OPs, classifying them into diffuse (physiological/racial pigmentations, smoker's
melanosis, drug-induced hyperpigmentation, post-inflammatory hyperpigmentation,
black hairy tongue, OPs associated to systemic diseases) and localized (amalgam
tattoo, melanocytic nevi, melanoacanthoma, melanosis) lesions.
PMID- 28421729
TI - Effects of TNF-alpha inhibitors in patients with psoriasis and metabolic
syndrome: a preliminary study.
AB - BACKGROUND: Psoriasis is an inflammatory disease, that is increasingly being
considered as a systemic disorder. Among associated comorbidities, metabolic
syndrome plays an important role. The effects of biological therapies on
metabolic syndrome is controversial. METHODS: Thirty-one psoriatic patients with
metabolic syndrome, eligible to treatment with anti-TNFalpha agents, were
enrolled. Metabolic parameters were measured during 4 subsequent visits, one
every 40 to 60 days. PASI, BSA and DLQI assessed the severity of psoriasis and
the impact on quality of life. RESULTS: We include 31 patients, 18 treated with
etanercept and 13 with adalimumab. Metabolic parameters evaluated at V4 in both
groups showed different trends in the blood glucose values: a slight decrease in
adalimumab group, an increase in etanercept group, with an almost significant
comparison test (p=0.073). Similarly, the lipid profile revealed an opposing
trend, with an increase in triglycerides in adalimumab patients, and a decrease
in the other group, without statistically significant differences. No
statistically significant difference was recorded in HDL cholesterol. An
improvement in systolic and diastolic pressure was appreciated in both groups,
although not significantly. The waist circumference slightly decreased in both
groups. PASI 75 score was reached in 60% of the patients. In addition, BSA and
DLQI improved. CONCLUSIONS: Our study showed a slight improvement of metabolic
parameters, at times with a trend toward significance. Additional long-term
studies and a larger number of patients are needed to more clearly define the
association between psoriasis and cardiovascular disease and understand the
effect of biological therapies on metabolic parameters.
PMID- 28421730
TI - Facies: the value of an old diagnostic tip in pediatric dermatology.
AB - The authors examine what is meant as facies in medicine. After an introduction to
the word's understanding, they move on listing some dermatological conditions
associated to peculiar facies in the child. Starting from atopic dermatitis, the
authors develop an algorithm including Genodermatoses, Neurocutaneous Disorders,
and Multiple Congenital Anomalies Syndromes. They emphasize the distinctive
features of the lesions on the face and their fundamental diagnostic importance.
PMID- 28421731
TI - Intraoperative dexmedetomidine sedation reduces the postoperative agitated
behavior in elderly patients undergoing orthopedic surgery compared to the
propofol sedation.
AB - BACKGROUND: Postoperative agitation or confusion is one of the symptoms of
hyperactive delirium in elderly patients. We retrospectively evaluated the
incidence of postoperative abnormal psychomotor behavior in elderly surgical
patients according to the use of different intraoperative sedative agents:
dexmedetomidine vs. propofol. METHODS: The medical records of 855 elderly
patients, who underwent orthopedic surgery with regional anesthesia between July
2012 and September 2015, were divided into two groups, the dexmedetomidine group
(N.=263) and the propofol group (N.=592), and then evaluated. Agitated behavior
was evaluated as the primary outcome, and patient-, surgery-, and anesthesia
related factors, as well as other postoperative complications, were investigated
as secondary outcomes. To reduce the risk of confounder effects between the two
groups, 263 patients were selected from the propofol group by propensity score
matching. RESULTS: In the propensity-score-matched groups, the incidence of
agitated behavior was lower in the dexmedetomidine group compared with the
propofol group (6 [2.3%] vs. 17 [6.5%], P=0.027). All pre- and postoperative
laboratory values were comparable between the two groups, including hemoglobin,
hematocrit, platelet count, C-reactive protein, electrolytes, creatinine,
glomerular filtration rate, and albumin. Moreover, intraoperative propofol
sedation, older age, higher Charlson comorbidity index, and hip surgery were
found to be significant factors for the occurrence of agitation. CONCLUSIONS:
This study suggests that intraoperative dexmedetomidine sedation, as compared
with propofol sedation, may have a greater beneficial effect in reducing agitated
behavior in elderly patients undergoing orthopedic surgery with regional
anesthesia.
PMID- 28421732
TI - Comparison of absolute fluid restriction versus relative volume redistribution
strategy in low central venous pressure anesthesia in liver resection surgery: a
randomized controlled trial.
AB - BACKGROUND? Lowering central venous pressure (CVP) can decrease blood loss during
liver resection and it is associated with improved outcomes. Multiple CVP
reducing maneuvers have been described, but direct comparison of their
effectiveness and safety has never been performed. METHODS? Patients undergoing
resections of two or more liver segments were equally randomized to absolute
fluid restriction (AR, N.=17) or relative volume redistribution group (RR,
N.=17). The ease of reaching low CVP, blood loss, morbidity and mortality were
assessed. Besides, the effect of Pringle maneuver and utility of stroke volume
variation (SVV) were analyzed. RESULTS? Both methods of CVP reduction were
equally effective (0.7+/-0.9 vs. 0.9+/-1.0 protocolized steps in the AR and RR
group; P=0.356) and safe (no difference in observed blood loss, intraoperative
hemodynamic parameters, lactate levels, morbidity and mortality). Patients in the
AR group received smaller amount of fluids in the pre-resection period (120 (100
150) vs. 600 (500-700) mL; P<0.001), and had slightly longer hospital stay (10 [8
14] vs. 8 [7-11]; P=0.045). Low CVP was predicted by SVV>10% with 81.4%
sensitivity and 77.1% specificity. Reduced blood loss and transfusion rate was
observed when Pringle maneuver was used. CONCLUSIONS? In our study, absolute
fluid restriction and relative volume redistribution seemed to be equally
effective and safe methods of lowering CVP in patients undergoing liver
resection. According to our data high SVV might be considered as a low CVP
replacement. Pringle maneuver reduced blood loss and transfusion requirement.
PMID- 28421733
TI - Beyond high-flow oxygen therapy to manage the hazards of intubation and prevent
desaturation.
PMID- 28421734
TI - Pediatric cuffed tracheal tubes: the advantage of a deflation-in-action maneuver.
PMID- 28421735
TI - Self-Healable and Cold-Resistant Supercapacitor Based on a Multifunctional
Hydrogel Electrolyte.
AB - Excellent self-healability and cold resistance are attractive properties for a
portable/wearable energy-storage device. However, achieving the features is
fundamentally dependent on an intrinsically self-healable electrolyte with high
ionic conduction at low temperature. Here we report such a hydrogel electrolyte
comprising sodium alginate cross-linked by dynamic catechol-borate ester bonding.
Since its dynamically cross-linked alginate network can tolerate high-content
inorganic salts, the electrolyte possesses excellent healing
efficiency/cyclability but also high ionic conduction at both room temperature
and low temperature. A supercapacitor with the multifunctional hydrogel
electrolyte completely restores its capacitive properties even after
breaking/healing for 10 cycles without external stimulus. At a low temperature of
-10 degrees C, the capacitor is even able to maintain at least 80% of its room
temperature capacitance. Our investigations offer a strategy to assemble self
healable and cold-resistant energy storage devices by using a multifunctional
hydrogel electrolyte with rationally designed polymeric networks, which has
potential application in portable/wearable electronics, intelligent apparel or
flexible robot, and so on.
PMID- 28421736
TI - Enhancing the Bioactivity of Yttria-Stabilized Tetragonal Zirconia Ceramics via
Grain-Boundary Activation.
AB - Yttria-stabilized tetragonal zirconia (Y-TZP) has been proposed as a potential
dental implant because of its good biocompatibility, excellent mechanical
properties, and distinctive aesthetic effect. However, Y-TZP cannot form chemical
bonds with bone tissue because of its biological inertness, which affects the
reliability and long-term efficacy of Y-TZP implants. In this study, to improve
the bioactivity of Y-TZP ceramics while maintaining their good mechanical
performance, Y-TZP was modified by grain-boundary activation via the infiltration
of a bioactive glass (BG) sol into the surface layers of Y-TZP ceramics under
different negative pressures (atmospheric pressure, -0.05 kPa, and -0.1 kPa),
followed by gelling and sintering. The in vitro bioactivity, mechanical
properties, and cell behavior of the Y-TZP with improved bioactivity were
systematically investigated using X-ray diffraction (XRD), scanning electron
microscopy (SEM), energy-dispersive spectrometry (EDS), electron probe
microanalysis (EPMA), and Raman spectroscopy. The results of the bioactivity test
conducted by immersing Y-TZP in simulated body fluid (SBF) showed that a bonelike
apatite layer was produced on the entire surface. The mechanical properties of
the modified Y-TZP decreased as the negative pressure in the BG-infiltration
process increased relative to those of the Y-TZP blank group. However, the
samples infiltrated with the BG sol under -0.05 kPa and atmospheric pressure
still retained good mechanical performance. The cell-culture results revealed
that the bioactive surface modification of Y-TZP could promote cell adhesion and
differentiation. The present work demonstrates that the bioactivity of Y-TZP can
be enhanced by grain-boundary activation, and the bioactive Y-TZP is expected to
be a potential candidate for use as a dental implant material.
PMID- 28421737
TI - Modeling of Stresses and Strains during (De)Lithiation of Ni3Sn2-Coated Nickel
Inverse-Opal Anodes.
AB - Tin alloy-based anodes supported by inverse-opal nanoscaffolds undergo large
volume changes from (de)lithiation during cyclic battery (dis)charging, affecting
their mechanical stability. We perform continuum mechanics-based simulation to
study the evolution of internal stresses and strains as a function of the
geometry of the active layer(s): (i) thickness of Ni3Sn2 single layer (30 and 60
nm) and (ii) stacking sequence of Ni3Sn2 and amorphous Si in bilayers (60 nm
thick). For single Ni3Sn2 active layers, a thinner layer displays higher strains
and stresses, which are relevant to mechanical stability, but causes lower
strains and stresses in the Ni scaffold. For Ni3Sn2-Si bilayers, the stacking
sequence significantly affects the deformation of the active layers and thus its
mechanical stability due to different lithiation behaviors and volume changes.
PMID- 28421738
TI - Targeting the Nrf2/Amyloid-Beta Liaison in Alzheimer's Disease: A Rational
Approach.
AB - Amyloid is a prominent feature of Alzheimer's disease (AD). Yet, a linear linkage
between amyloid-beta peptide (Abeta) and the disease onset and progression has
recently been questioned. In this context, the crucial partnership between Abeta
and Nrf2 pathways is acquiring paramount importance, offering prospects for
deciphering the Abeta-centered disease network. Here, we report on a new class of
antiaggregating agents rationally designed to simultaneously activate
transcription-based antioxidant responses, whose lead 1 showed interesting
properties in a preliminary investigation. Relying on the requirements of Abeta
recognition, we identified the catechol derivative 12. In SH-SY5Y neuroblastoma
cells, 12 combined remarkable free radical scavenger properties to the ability to
trigger the Nrf2 pathway and induce the Nrf2-dependent defensive gene NQO1 by
means of electrophilic activation of the transcriptional response. Moreover, 12
prevented the formation of cytotoxic stable oligomeric intermediates, being
significantly more effective, and per se less toxic, than prototype 1. More
importantly, as different chemical features were exploited to regulate Nrf2 and
Abeta activities, the two pathways could be tuned independently. These findings
point to compound 12 and its derivatives as promising tools for investigating the
therapeutic potential of the Nrf2/Abeta cellular network, laying foundation for
generating new drug leads to confront AD.
PMID- 28421740
TI - Enhancing the Performance of Quantum Dot Light-Emitting Diodes Using Room
Temperature-Processed Ga-Doped ZnO Nanoparticles as the Electron Transport Layer.
AB - Colloidal ZnO nanoparticle (NP) films are recognized as efficient electron
transport layers (ETLs) for quantum dot light-emitting diodes (QD-LEDs) with good
stability and high efficiency. However, because of the inherently high work
function of such films, spontaneous charge transfer occurs at the QD/ZnO
interface in such a QD-LED, thus leading to reduced performance. Here, to improve
the QD-LED performance, we prepared Ga-doped ZnO NPs with low work functions and
tailored band structures via a room-temperature (RT) solution process without the
use of bulky organic ligands. We found that the charge transfer at the interface
between the CdSe/ZnS QDs and the doped ZnO NPs was significantly weakened because
of the incorporated Ga dopants. Remarkably, the as-assembled QD-LEDs, with Ga
doped ZnO NPs as the ETLs, exhibited superior luminances of up to 44 000 cd/m2
and efficiencies of up to 15 cd/A, placing them among the most efficient red
light QD-LEDs ever reported. This discovery provides a new strategy for
fabricating high-performance QD-LEDs by using RT-processed Ga-doped ZnO NPs as
the ETLs, which could be generalized to improve the efficiency of other
optoelectronic devices.
PMID- 28421739
TI - Ultraefficient Cap-Exchange Protocol To Compact Biofunctional Quantum Dots for
Sensitive Ratiometric Biosensing and Cell Imaging.
AB - An ultraefficient cap-exchange protocol (UCEP) that can convert hydrophobic
quantum dots (QDs) into stable, biocompatible, and aggregation-free water
dispersed ones at a ligand:QD molar ratio (LQMR) as low as 500, some 20-200-fold
less than most literature methods, has been developed. The UCEP works
conveniently with air-stable lipoic acid (LA)-based ligands by exploiting tris(2
carboxylethyl phosphine)-based rapid in situ reduction. The resulting QDs are
compact (hydrodynamic radius, Rh, < 4.5 nm) and bright (retaining > 90% of
original fluorescence), resist nonspecific adsorption of proteins, and display
good stability in biological buffers even with high salt content (e.g., 2 M
NaCl). These advantageous properties make them well suited for cellular imaging
and ratiometric biosensing applications. The QDs prepared by UCEP using
dihydrolipoic acid (DHLA)-zwitterion ligand can be readily conjugated with octa
histidine (His8)-tagged antibody mimetic proteins (known as Affimers). These QDs
allow rapid, ratiometric detection of the Affimer target protein down to 10 pM
via a QD-sensitized Forster resonance energy transfer (FRET) readout signal.
Moreover, compact biotinylated QDs can be readily prepared by UCEP in a facile,
one-step process. The resulting QDs have been further employed for ratiometric
detection of protein, exemplified by neutravidin, down to 5 pM, as well as for
fluorescence imaging of target cancer cells.
PMID- 28421741
TI - Uphill Water Transport on a Wettability-Patterned Surface: Experimental and
Theoretical Results.
AB - In nature, there exist many functional water-controlling surfaces, such as the
water-repellent surface of lotus leaves, the superhydrophobic water-adhesive
surface of rose petals, the water-harvesting surface of a beetle's back, and the
water-transporting surface of the legs of Ligia exotica. These natural surfaces
suggest that surface chemistry and hierarchical structures are essential for
controlling the water behavior. We have reported the preparation of
superhydrophobic and antireflection silicon nanospike-array structures using self
organized honeycomb-patterned films as three-dimensional dry-etching masks.
Moreover, the surface wettability of the silicon nanospike-array structures can
be easily transformed from superhydrophobic to superhydrophilic by changes in the
surface chemistry. In this report, we show the preparation of water-controlling
surfaces, such as water-harvesting and water-transporting surfaces, by the
wettability patterning of silicon nanostructured surfaces. We prepared honeycomb
patterned films for dry-etching masks made from polystyrene and an amphiphilic
polymer by casting a chloroform solution. After the fixation of the top layer of
the honeycomb-patterned films on a single-crystal silicon substrate, reactive ion
etching was performed. The as-prepared silicon nanospike-array structure showed
superhydrophobicity, and the water contact angles were over 170 degrees . After
UV-O3 treatment with photomasks, only the UV-irradiated surfaces showed
superhydrophilicity, suggesting that we can obtain superhydrophobic- and
superhydrophilic-patterned surfaces for which the patterns are the same as those
of the photomasks. On the basis of these wettability-patterned surfaces, we
demonstrated water harvesting by superhydrophilic dot-patterned surfaces and
water transportation against gravity by superhydrophilic triangular-patterned
surfaces. In particular, we investigated uphill water transport through the
motion of droplets on tilting slopes based on the equation of motion. These
results suggested that we can obtain superior microfluidic devices suitable for
various applications through the use of optional wettability patterns.
PMID- 28421742
TI - Mid-Gap States and Normal vs Inverted Bonding in Luminescent Cu+- and Ag+-Doped
CdSe Nanocrystals.
AB - Mid-gap luminescence in copper (Cu+)-doped semiconductor nanocrystals (NCs)
involves recombination of delocalized conduction-band electrons with copper
localized holes. Silver (Ag+)-doped semiconductor NCs show similar mid-gap
luminescence at slightly (~0.3 eV) higher energy, suggesting a similar
luminescence mechanism, but this suggestion appears inconsistent with the large
difference between Ag+ and Cu+ ionization energies (~1.5 eV), which should make
hole trapping by Ag+ highly unfavorable. Here, Ag+-doped CdSe NCs (Ag+:CdSe) are
studied using time-resolved variable-temperature photoluminescence (PL)
spectroscopy, magnetic circularly polarized luminescence (MCPL) spectroscopy, and
time-dependent density functional theory (TD-DFT) to address this apparent
paradox. In addition to confirming that Ag+:CdSe and Cu+:CdSe NCs display similar
broad PL with large Stokes shifts, we demonstrate that both also show very
similar temperature-dependent PL lifetimes and magneto-luminescence. Electronic
structure calculations further predict that both dopants generate similar
localized mid-gap states. Despite these strong similarities, we conclude that
these materials possess significantly different electronic structures.
Specifically, whereas photogenerated holes in Cu+:CdSe NCs localize primarily in
Cu(3d) orbitals, formally oxidizing Cu+ to Cu2+, in Ag+:CdSe NCs they localize
primarily in 4p orbitals of the four neighboring Se2- ligands, and Ag+ is not
oxidized. This difference reflects a shift from "normal" to "inverted" bonding
going from Cu+ to Ag+. The spectroscopic similarities are explained by the fact
that, in both materials, photogenerated holes are localized primarily within
covalent [MSe4] dopant clusters (M = Ag+, Cu+). These findings reconcile the
similar spectroscopies of Ag+- and Cu+-doped semiconductor NCs with the vastly
different ionization potentials of their Ag+ and Cu+ dopants.
PMID- 28421743
TI - Double-Enzymes-Mediated Bioluminescent Sensor for Quantitative and Ultrasensitive
Point-of-Care Testing.
AB - We report an ultrasensitive, quantitative, and rapid bioluminescent immunosensor
(ABS) for point-of-care testing (POCT) of the disease biomarker in clinical
samples using double enzymes including alkaline phosphatase (ALP) and luciferase.
In the presence of the biomarker, the ALP attached on the surface of immuno
nanocomplex dephosphorylates adenine triphosphate (ATP), subsequently inhibiting
the ATP-luciferin-luciferase bioluminescent reaction. The highly sensitive
response of ATP (picomolar level) allows for ultrasensitive detection of
biomarker via the effective change of the bioluminescence intensity through ALP-
and luciferase-catalyzed reactions, which can be quantitatively determined by a
portable ATP detector. This ABS fulfills the criteria for POCT that performs
sensitive (femtomolar level of biomarkers) and quantitative measurement quickly
(less than 1 h) with minimal equipment (portable detector).
PMID- 28421744
TI - A Mini HIP HOP Assay Uncovers a Central Role for Copper and Zinc in the
Antifungal Mode of Action of Allicin.
AB - Garlic contains the organosulfur compound allicin which exhibits potent
antifungal activity. Here we demonstrate the use of a highly simplified yeast
chemical genetic screen to characterize its mode of action. By screening 24
validated yeast gene deletion "signature" strains for which hypersensitivity is
characteristic for common antifungal modes of action, yeast lacking the high
affinity Cu2+ transporter Ctr1 was found to be hypersensitive to allicin.
Focusing on transition metal related genes identified two more hypersensitive
strains lacking the Cu2+ and Zn2+ transcription factors Mac1 and Zap1.
Hypersensitivity in these strains was reversed by the addition of Cu2+ and Zn2+
ions, respectively. The results suggest the antifungal activity of allicin is
mediated through restricted Cu2+ and Zn2+ uptake or inhibition of Cu2+ and Zn2+
metalloproteins. As certain antimicrobial modes of action are much more common
than others, the approach taken here provides a useful way to identify them early
on.
PMID- 28421745
TI - Molecular Approach to the Synergistic Effect on Astringency Elicited by Mixtures
of Flavanols.
AB - The interactions between salivary proteins and wine flavanols (catechin,
epicatechin, and mixtures thereof) have been studied by HPLC-DAD, isothermal
titration microcalorimetry, and molecular dynamics simulations. Chromatographic
results suggest that the presence of these flavanol mixtures could facilitate the
formation of precipitates to the detriment of soluble aggregates. Comparison
between the thermodynamic parameters obtained showed remarkably higher negative
values of DeltaG in the system containing the mixture of both flavanols in
comparison to the systems containing individual flavanols, indicating a more
favorable scenario in the mixing system. Also, the apparent binding constants
were higher in this system. Furthermore, molecular dynamics simulations suggested
a faster and greater cooperative binding of catechin and epicatechin to IB714
peptides when both types of flavanols are present simultaneously in solution.
PMID- 28421746
TI - Multifunctional Enzymatically Generated Hydrogels for Chronic Wound Application.
AB - The healing of chronic wounds requires intensive medical intervention at huge
healthcare costs. Dressing materials should consider the multifactorial nature of
these wounds comprising deleterious proteolytic and oxidative enzymes and high
bacterial load. In this work, multifunctional hydrogels for chronic wound
application were produced by enzymatic cross-linking of thiolated chitosan and
gallic acid. The hydrogels combine several beneficial to wound healing
properties, controlling the matrix metalloproteinases (MMPs) and myeloperoxidase
(MPO) activities, oxidative stress, and bacterial contamination. In vitro studies
revealed above 90% antioxidant activity, and MPO and collagenase inhibition by up
to 98 and 23%, respectively. Ex vivo studies with venous leg ulcer exudates
confirmed the inhibitory capacity of the dressings against MPO and MMPs.
Additionally, the hydrogels reduced the population of the most frequently
encountered in nonhealing wounds bacterial strains. The stable at physiological
conditions and resistant to lysozyme degradation hydrogels showed high
biocompatibility with human skin fibroblasts.
PMID- 28421747
TI - Multifunctional Probe Based on Cationic Conjugated Polymers for Nitroreductase
Related Analysis: Sensing, Hypoxia Diagnosis, and Imaging.
AB - Nitroreductase (NTR) is overexpressed in hypoxic tumors. Moreover, hypoxia is
usually considered as the most important feature of various diseases. Thus, it is
important to build a sensitive and selective method for NTR detection and hypoxia
diagnosis. Herein, a new cationic conjugated polymer (PBFBT-NP) with p
nitrophenyl group in the side chain was designed and synthesized as a fluorescent
probe for the detection of NTR. In the absence of NTR, the fluorescence of PBFBT
NP was quenched due to photoinduced electron transfer (PET). On the contrary, in
the presence of NTR, NTR can specifically react with p-nitrophenyl group to form
p-aminophenyl group, which leads to the PET being inhibited and the polymer's
fluorescence significantly increasing (>110-fold). The sensitive and selective
NTR sensing method in vitro is thus constructed with a low detection limit of 2.9
ng/mL. Moreover, the hypoxic status of tumor cells can be visualized by
fluorescence bioimaging with very low cytotoxicity. Interestingly, the probe was
successfully used for imaging an NTR-expressed microorganism, such as E. coli,
and showed excellent antibacterial activity against E. coli under white light
irradiation. In brief, this multifunctional probe is promising for widespread use
in NTR-related biological analysis.
PMID- 28421748
TI - Potential Contribution of Fish Feed and Phytoplankton to the Content of Volatile
Terpenes in Cultured Pangasius (Pangasianodon hypophthalmus) and Tilapia
(Oreochromis niloticus).
AB - Geosmin and 2-methylisoborneol are the most recognized off-flavors in freshwater
fish, but terpenes may also contribute off-flavor in fish. We identified six
monoterpenes, 11 sesquiterpenes, and three terpene-related compounds in pangasius
and tilapia from aquaculture farms in Bangladesh. The concentrations of most of
the volatiles were below published odor thresholds, except for alpha-pinene,
limonene, beta-caryophyllene, alpha-humulene, and beta-ionone in tilapia, and
limonene and beta-ionone in pangasius. To identify sources of the terpenes,
terpene profiles of fish feed and phytoplankton in the ponds were analyzed. In
feed and mustard cake (feed ingredient), five monoterpenes and two sesquiterpenes
were identified, and five of these compounds were also detected in the fish. In
phytoplankton, 11 monoterpenes were found and three also occurred in the fish.
The higher number of terpenes common to both fish and feed, than to fish and
phytoplankton, suggests that feed was a more abundant source of odor-active
terpenes in the fish than phytoplankton.
PMID- 28421749
TI - Design of Multifunctional Nanogate in Response to Multiple External Stimuli Using
Amphiphilic Diblock Copolymer.
AB - Nature uses the interplay between hydrophobic and electrostatic interactions of
disordered proteins to orchestrate complicated molecular gates such as the
nuclear pore complex to control the transport of biological masses. Inspired by
nature, we here theoretically show that well-defined gate shape, sensitive
response to pH and salt concentration, and selectivity in cargo transport can be
simultaneously achieved by grafting amphiphilic diblock copolymers made of
sequence-controlled hydrophobic and ionizable monomers on the inner surface of
solid-state nanopore. As a result, multiple functions such as ionic gating and
molecular filtering can be implemented into one single copolymer nanogate. The
gate structure and thermodynamics is a result of the self-assembly of the
sequence-designed copolymer in the confined geometry that minimizes the free
energy of the system. Our theory further predicts a phase transition and
discontinuous charge regulation of the confined copolymer that allows logical
gating in biosensors and nanofluidic devices. As an example of application, a
nanolocker with the potential of molecular pumping has also been designed with
the cooperation of two amphiphilic copolymer gates. Our results highlight the
importance of polymer sequence in nanogating, and these insights can be used to
guide the rational design of polymer-coated smart nanopores.
PMID- 28421750
TI - How Frequently Are Pan-Assay Interference Compounds Active? Large-Scale Analysis
of Screening Data Reveals Diverse Activity Profiles, Low Global Hit Frequency,
and Many Consistently Inactive Compounds.
AB - Undetected pan-assay interference compounds (PAINS) with false-positive
activities in assays often propagate through medicinal chemistry programs and
compromise their outcomes. Although a large number of PAINS have been classified,
often on the basis of individual studies or chemical experience, little has been
done so far to systematically assess their activity profiles. Herein we report a
large-scale analysis of the behavior of PAINS in biological screening assays.
More than 23 000 extensively tested compounds containing PAINS substructures were
detected, and their hit rates were determined. Many consistently inactive
compounds were identified. The hit frequency was low overall, with median values
of two to five hits for PAINS tested in hundreds of assays. Only confined subsets
of PAINS produced abundant hits. The same PAINS substructure was often found in
consistently inactive and frequently active compounds, indicating that the
structural context in which PAINS occur modulates their effects.
PMID- 28421751
TI - Formation and Characterization of Homoleptic Thorium Isocyanide Complexes.
AB - Homoleptic thorium isocyanide complexes have been prepared via the reactions of
laser-ablated thorium atoms and (CN)2 in a cryogenic matrix, and the structures
of the products were characterized by infrared spectroscopy and theoretical
calculations. Thorium atoms reacted with (CN)2 under UV irradiation to form the
oxidative addition product Th(NC)2, which was calculated to have closed-shell
singlet ground state with a bent geometry. Further reaction of Th(NC)2 and (CN)2
resulted in the formation of Th(NC)4, a molecule with a tetrahedral geometry.
Minor products such as ThNC and Th(NC)3 were produced upon association reactions
of CN with Th and Th(NC)2. Homoleptic thorium cyanide isomers Th(CN)x (x = 1-4)
are predicted to be less stable than the corresponding isocyanides. The C-N
stretches of thorium cyanides were calculated to be between 2170 and 2230 cm-1 at
the B3LYP level, more than 120 cm-1 higher than the N-C stretches of isocyanides
and with much weaker intensities. No experimental absorptions appeared where
Th(CN)x should be observed.
PMID- 28421752
TI - Consecutive Sonogashira Coupling and Hydroamination Cyclization for the Synthesis
of Isoindolo[1,2-b]quinazolin-10(12H)-ones Catalyzed by CuI/l-Proline.
AB - A consecutive Sonogashira coupling reaction, acetylene hydroamination cyclization
of 2-(2-bromophenyl)quinazolin-4(3H)-ones and terminal alkynes, is described
catalyzed by CuI/l-proline in the presence of Cs2CO3. This procedure provided a
facile method for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-one
derivatives in good yields.
PMID- 28421753
TI - Ruthenium(II)-Catalyzed Redox-Neutral [3+2] Annulation of Indoles with Internal
Alkynes via C-H Bond Activation: Accessing a Pyrroloindolone Scaffold.
AB - Ru(II)-catalyzed redox-neutral [3+2] annulation reactions of N-ethoxycarbamoyl
indoles and internal alkynes via C-H bond activation are reported. This method
features a broad internal alkyne scope, including various aryl/alkyl-,
alkyl/alkyl-, and diaryl-substituted alkynes, good to excellent regioselectivity,
diverse functional group tolerance, and mild reaction conditions. The N
ethoxycarbamoyl directing group, temperature, CsOAc, and ruthenium catalyst
proved to be crucial for conversion and high regioselectivity. Additionally,
preliminary mechanistic experiments were conducted, and a possible mechanism was
proposed.
PMID- 28421754
TI - Orbicularisine: A Spiro-Indolothiazine Isolated from Gills of the Tropical
Bivalve Codakia orbicularis.
AB - A novel spiro-indolofuranone fused to a thiazine skeleton, orbicularisine (1),
was isolated from gills of the mollusk Codakia orbicularis. The isolation and
structure elucidation using spectroscopic evidence including mass and NMR
spectroscopy are described. The final structure of 1 was supported by key HMBC
correlation.
PMID- 28421755
TI - Increasing Radical Character of Large [n]cyclacenes Unveiled by Wave Function
Theory.
AB - We have investigated the radicality and the vertical singlet-triplet energy gap
of [n]cyclacenes (cyclic polyacenes) as a function of the system size for n even,
from 6 to 22. The calculations are performed using the complete active space self
consistent field method and second-order n-electron valence perturbation theory.
We present a systematic way for the selection of the active space in order to
have a balanced description of the wave function as the size of the system
increases. Moreover, we provide didactic insight into the failure of an approach
based on a minimal active space. We find that the ground state is an open-shell
singlet and its multireference character increases progressively with n. The
singlet-triplet gap decreases as a function of the system size and approaches a
finite positive value for the limit n -> infinity. Finally, an analysis based on
the one-particle reduced density matrix suggests a polyradical character for the
largest cyclacenes.
PMID- 28421756
TI - Reactions of Copper and Silver Cations with Carbon Dioxide: An Infrared
Photodissociation Spectroscopic and Theoretical Study.
AB - The reaction of copper and silver cations with carbon dioxide was studied by mass
selected infrared photodissociation spectroscopy. Quantum chemical calculations
were performed on these products, which aided the experimental assignments of the
infrared spectra and helped to elucidate the geometrical and electronic
structures. The Cu+ and Ag+ cations bind to an oxygen atom of CO2 in an end-on
configuration via a charge-quadrupole electrostatic interaction in the [M(CO2)n]+
complexes. The formation of oxide-carbonyl and carbonyl-carbonate structures is
not favored for the interaction of CO2 with Cu+ and Ag+. For n = 3 and 4, the n +
0 structure is preferred. [Note on the nomenclature: Using i + j, i denotes the
number of CO2 molecules in the first coordination shell, and j denotes the number
of CO2 molecules in the second coordination shell.] The two nearly energy
identical n + 0 and (n - 1) + 1 structures coexist in n = 5 and 6. While the six
coordinated structure is favored for [Cu(CO2)n=7,8]+, the n + 0 configuration is
dominated in [Ag(CO2)n=7,8]+. The reaction of CO2 with the cationic metal atoms
has been compared to that with the neutral and anionic metal atoms, which would
have important implications for understanding the interaction of CO2 with
reduction catalysts and rationally designing catalysts for CO2 reduction based on
cost-effective transition metals.
PMID- 28421757
TI - A Bulky Disulfoxide Ligand for Pd-Catalyzed Oxidative Allylic C-H Amination with
2,2,2-Trichloroethyl Tosyl Carbamate.
AB - Challenging substrates and conditions in homogeneous catalysis pose stringent
demands on the ligands used. A novel, bulky, 1-adamantyl-substituted disulfoxide
ligand designed after a systematic evaluation of the electronic and steric
properties of disulfoxide substituents permits the allylic oxidative C-N coupling
reaction to proceed at lower catalyst loading while requiring a smaller excess of
reagents. Additionally, this ligand improves the yields when TsNHCOOCH2CCl3, a
novel reagent that permits deprotection of the products under both acidic and
basic conditions, is used.
PMID- 28421758
TI - Copper(II)-Mediated Chelation-Assisted Regioselective N-Naphthylation of Indoles,
Pyrazoles and Pyrrole through Dehydrogenative Cross-Coupling.
AB - A copper-mediated picolinamide directed regioselective cross-coupling of
naphthylamines with azoles is developed via C-H functionalization and C-N bond
formation. The reaction of indoles leads to the formation of chiral C-N cross
coupled products with functional group tolerance. These reaction conditions can
also be extended to the cross-coupling of pyrazole and pyrrole scaffolds.
PMID- 28421759
TI - Is the Accuracy of Density Functional Theory for Atomization Energies and
Densities in Bonding Regions Correlated?
AB - The development of approximate exchange-correlation functionals is critical for
modern density functional theory. A recent analysis of atomic systems suggested
that some modern functionals are straying from the path toward the exact
functional because electron densities are becoming less accurate while energies
are becoming more accurate since the year 2000. To investigate this trend for
more chemically relevant systems, the electron densities in the bonding regions
and the atomization energies are analyzed for a series of diatomic molecules with
90 different functionals. For hybrid generalized gradient approximation
functionals developed since the year 2000, the errors in densities and
atomization energies are decoupled; the accuracy of the energies remains
relatively consistent while the accuracy of the densities varies significantly.
Such decoupling is not observed for generalized gradient and meta-generalized
gradient approximation functionals. Analysis of electron densities in bonding
regions is found to be important for the evaluation of functionals for chemical
systems.
PMID- 28421760
TI - Transient Resonance Raman Spectroscopy of a Light-Driven Sodium-Ion-Pump
Rhodopsin from Indibacter alkaliphilus.
AB - Sodium-ion-pump rhodopsin (NaR) is a microbial rhodopsin that transports Na+
during its photocycle. Here we explore the photocycle mechanism of NaR from
Indibacter alkaliphilus with transient absorption and transient resonance Raman
spectroscopy. The transient absorption data indicate that the photocycle of NaR
is K (545 nm) -> L (490 nm)/M (420 nm) -> O1 (590 nm) -> O2 (560 nm) -> NaR,
where the L and M are formed as equilibrium states. The presence of K, L, M, and
O intermediates was confirmed by the resonance Raman spectra with 442 and 532 nm
excitation. The main component of the transient resonance Raman spectra was due
to L which contains a 13-cis retinal protonated Schiff base. The presence of an
enhanced hydrogen out-of-plane band as well as its sensitivity to the H/D
exchange indicate that the retinal chromophore is distorted near the Schiff base
region in L. Moreover, the retinal Schiff base of the L state forms a hydrogen
bond that is stronger than that of the dark state. These observations are
consistent with a Na+ pumping mechanism that involves a proton transfer from the
retinal Schiff base to a key aspartate residue (Asp116 in Krokinobacter eikastus
rhodopsin 2) in the L/M states.
PMID- 28421761
TI - Diversity-Oriented One-Pot Synthesis to Construct Functionalized Chroman-2-one
Derivatives and Other Heterocyclic Compounds.
AB - The asymmetric organocatalyzed diversity-oriented one-pot synthesis has been
developed to construct chroman-2-one derivatives and other heterocyclic compounds
with excellent efficiency and stereoselectivity. The reactions represent a
challenging issue, since it altered the inherent selectivity profiles exhibited
by the substrates of 2-hydroxycinnamaldehyde 1 and trans-beta-nitrostyrene 2,
which was previously reported as the asymmetric oxa-Michael-Michael cascade to
generate chiral chromans. It should be noted that polycyclic O,O-acetal
containing compounds, which are found in numerous natural products and
biologically interesting molecules, could also be achieved in good yields with
excellent enantioselectivity as a single diastereoisomer with five continuous
stereogenic centers.
PMID- 28421762
TI - Cinchona Alkaloid Catalyzed Enantioselective [4 + 2] Annulation of Allenic Esters
and in Situ Generated ortho-Quinone Methides: Asymmetric Synthesis of
Functionalized Chromans.
AB - A novel enantioselective [4 + 2] annulation of the allenoates having a unique
positive ortho-effect with in situ generated ortho-quinone methides has been
developed under the catalysis of Cinchona alkaloid. This chiral amine-catalyzed
reaction provides an alternative route to asymmetric catalytic construction of
synthetically interesting, highly functionalized chiral chromans in good to
excellent enantioselectivities (up to 97% ee).
PMID- 28421763
TI - Synthetic Approaches to the New Drugs Approved During 2015.
AB - New drugs introduced to the market every year represent privileged structures for
particular biological targets. These new chemical entities (NCEs) provide insight
into molecular recognition while serving as leads for designing future new drugs.
This annual review describes the most likely process-scale synthetic approaches
to 29 new chemical entities (NCEs) that were approved for the first time in 2015.
PMID- 28421764
TI - Total Synthesis of the Claimed Structure of (+/-)-Hyptinin and Structural
Revision of Natural Hyptinin.
AB - A total synthesis of (+/-)-hyptinin was achieved via a convergent route using the
key phosphonate, cyclic ketone, and aryl Grignard components. The 1H and 13C NMR
spectra of natural hyptinin did not agree with those of the synthesized compound.
In particular, there were considerable differences between the signals assigned
to the protons and carbons surrounding the lactone carbonyl group for the natural
and synthesized compounds. The NMR data strongly suggested that the naturally
occurring compound, hyptinin, was a structural isomer of the synthesized
compound. The structure of the natural compound was eventually established as (+)
beta-apopicropodophyllin, based on the synthesis results.
PMID- 28421765
TI - Singlet Fission in Weakly Interacting Acene Molecules.
AB - The energy conversion in solar cells has conventionally been limited by the
Shockley-Queisser limit. Singlet fission (SF), a decay mechanism where a single
excited singlet state is converted into two triplet states, can drastically
improve this efficiency. For the most part, observation of SF has been limited to
crystalline structures in solids and films, where strong ordering was present.
Here we report on singlet fission in a disordered system where organic
chromophores are distributed on the surface of a rare gas cluster. In this case,
the intermolecular distances and degree of excitation can be varied to obtain
their effects on the rate of singlet fission. We introduce a kinematic model that
takes into account the details of the geometrical arrangement of the system as
well as the time-dependent populations of the relevant states of each molecule
and evaluate the trends obtained by SF on the experimental observables.
PMID- 28421766
TI - Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H.
AB - Total syntheses of three different lamellarins have been accomplished using a
Ru(II)-catalyzed (3 + 2) annulation strategy to construct the central pyrrole
ring. The striking features of this synthesis are the use of PEG-400 as a green
solvent for the (3 + 2) annulation reaction and multiple catalytic reactions with
excellent overall yield. The present route also enables the synthesis of various
lamellarin analogues devoid of a B ring.
PMID- 28421767
TI - Base Layer Influence on Protonated Aminosilane Gradient Wettability.
AB - Protonated amine gradients have been prepared on silicon wafers via programmed
controlled rate infusion (CRI) with varying degrees of hydrophobicity and
characterized by X-ray photoelectron spectroscopy (XPS) and static and Wilhelmy
plate dynamic contact angle measurements. Initially, base layers were spin coated
from sols containing tetramethoxysilane (TMOS) and either phenyltrimethoxysilane
(PTMOS), dimethyldimethoxysilane (DMDMOS), or octyltrimethoxysilane (OTMOS, C8).
Amine gradients were then prepared from 3-aminopropyltriethoxysilane (APTEOS) via
CRI. Gradients were exposed to concentrated HCl vapor for amine protonation. XPS
showed that NH2 functional groups were distributed in a gradient fashion as a
result of CRI controlling the time of exposure to APTEOS. Interestingly, the
overall extent of N modification depended on the type of base layer used for
gradient formation. The C8-derived base layer had about half the amount of
nitrogen on the surface as compared to those prepared from TMOS, which was
attributed to a reduction in the number and accessibility of surface silanol
groups. The wettability and contact angle (CA) hysteresis were also dependent on
the base layer and varied along the length of the gradient. The greatest CA
change across the length of the gradient was observed on the gradient formed on
the C8-derived base layer. Likewise, the CA hysteresis was approximately 2 times
larger on the C8-modified surfaces, indicative of greater chemical inhomogeneity.
In contrast to uniformly modified substrates, Wilhelmy plate CA analysis that
involves the immersion of samples gave a unique S-shaped CA distance curve for
the gradients. The three curve segments correspond to hydrophilic, hydrophobic,
and a middle connecting region. Importantly, these curves give precise CAs along
the gradient that reflect the surface chemistry and coverage defined by
programmed CRI processing.
PMID- 28421768
TI - Synthesis, Structure, and Properties of Tetrabenzo[7]circulene.
AB - Tetrabenzo[7]circulene, a new member of aromatic saddles, was conveniently
synthesized from 2-(1-naphthoyl)benzoic acid with the seven-membered ring
constructed at an early stage of the synthesis. This method, upon minor
modification, was also useful for synthesis of thiophene-annulated [7]circulenes.
The structures of tetrabenzo[7]circulene and [7]circulene were compared in terms
of symmetry, flexibility, and curvature on the basis of DFT calculations and X
ray crystallography. It was also found that tetrabenzo[7]circulene functioned as
a p-type semiconductor in thin-film transistors and cocrystallized with C60.
PMID- 28421769
TI - X-ray Absorption and Electron Paramagnetic Resonance Guided Discovery of the Cu
Catalyzed Synthesis of Multiaryl-Substituted Furans from Aryl Styrene and Ketones
Using DMSO as the Oxidant.
AB - The first example of DMSO serving not only as a solvent but also as an oxidant to
promote the oxidation of Cu(I) to Cu(II) has been demonstrated. X-ray absorption
and electron paramagnetic resonance evidence revealed a single-electron redox
process where DMSO could oxidize Cu(I) to Cu(II). The novel discovery guided the
rational design of copper-catalyzed oxidative cyclization of aryl ketones with
styrenes to furans, providing a new method for the synthesis of multiaryl
substituted furans from cheap and readily available starting materials.
PMID- 28421770
TI - Selective Synthesis of (E)- and (Z)-Allyl Nitriles via Decarboxylative Reactions
of Alkynyl Carboxylic Acids with Azobis(alkylcarbonitriles).
AB - Allyl nitriles were synthesized from the reactions of arylpropiolic acids with
azobis(alkylcarbonitriles) (AIBN or ACCN). In the presence of Cu(OAc)2 as a
catalyst and pyridine as the solvent, the (E)-stereoisomer was formed as the
major product. This transformation shows good tolerance toward alkoxy, halogen,
alcohol, amine, ester, and ketone functional groups. When the reaction was
conducted with the sterically bulky amine, ethyldiisopropylamine, in the absence
of a copper catalyst, the corresponding (Z)-stereoisomers were formed
preferentially.
PMID- 28421771
TI - Marangoni Contraction of Evaporating Sessile Droplets of Binary Mixtures.
AB - The Marangoni contraction of sessile drops of a binary mixture of a volatile and
a nonvolatile liquid has been investigated experimentally and theoretically. The
origin of the contraction is the locally inhomogeneous evaporation rate of
sessile drops. This leads to surface tension gradients and thus to a Marangoni
flow. Simulations show that the interplay of Marangoni flow, capillary flow,
diffusive transport, and evaporative losses can establish a quasistationary drop
profile with an apparent nonzero contact angle even if both liquid components
individually wet the substrate completely. Experiments with different solvents,
initial mass fractions, and gaseous environments reveal a previously unknown
universal power-law relation between the apparent contact angle and the relative
undersaturation of the ambient atmosphere: thetaapp ~ (RHeq - RH)1/3. This
experimentally observed power law is in quantitative agreement with simulation
results. The exponent can also be inferred from a scaling analysis of the
hydrodynamic-evaporative evolution equations of a binary mixture of liquids with
different volatilities.
PMID- 28421772
TI - Acid-Mediated Intermolecular [3 + 2] Cycloaddition toward Pyrrolo[2,1
a]isoquinolines: Total Synthesis of the Lamellarin Core and Lamellarin G
Trimethyl Ether.
AB - A novel one-pot reaction has been developed for the efficient synthesis of
pyrrolo[2,1-a]isoquinolines and 1-dearyllamellarin core from (E)-(2
nitrovinyl)benzenes and azomethine ylides generated in situ. This strategy
provides a concise total synthesis of the lamellarin core and lamellarin G
trimethyl ether using electrophilic substitution and palladium-catalyzed Suzuki
Miyaura cross-coupling reactions.
PMID- 28421773
TI - Exploring Jolkinol D Derivatives To Overcome Multidrug Resistance in Cancer.
AB - Macrocyclic monoacyl lathyrane derivatives bearing a benzoyl moiety were
previously found to be strong ABCB1 modulators. To explore the effects of
different substituents of the aromatic moiety, 14 new compounds (1.1-1.7, 1.10,
and 2.1-2.4) were prepared from jolkinol D (1), obtained from Euphorbia
piscatoria, and from jolkinodiol (2), its hydrolysis derivative. Compounds 1.8
and 1.9, having aliphatic moieties, were also obtained. The reversal of ABCB1
mediated MDR was evaluated through functional and chemosensitivity assays on the
human ABCB1-gene-transfected L5178Y mouse T-lymphoma cell line. Structure
activity relationships showed that addition of electron-donating groups to the
aromatic moiety improved the activity. The effects on the ATPase activity of the
strongest modulator (1.3) and the inactive jolkinol D (1) were also investigated
and compared. Moreover, in the chemosensitivity assay, most of the compounds
interacted synergistically with doxorubicin. Compounds 1.1-1.10 and 2.1-2.4 were
further assessed for their collateral sensitivity effect against the human cancer
cells: EPG85-257 (gastric) and EPP85-181 (pancreatic), and the matching drug
selected cells EPG85-257RDB, EPG85-257RNOV, EPP85-181RDB, and EPP85-181RNOV. The
most promising ones (1.8 and 1.10) along with compound 3, previously selected,
were investigated as apoptosis inducers. The compounds were able to induce
apoptosis through caspase-3 activation, with significant differences being
observed between the parental and resistant cells.
PMID- 28421774
TI - Cost-effectiveness studies, a necessary tool in clinical nutrition in the XXI
century
PMID- 28421775
TI - Growth charts: which are the appropriate?
PMID- 28421776
TI - Drugs via enteral feeding tubes in inpatients: dispersion analysis and safe use
of dispensers.
AB - OBJECTIVE: This study aimed to improve knowledge about drug administration
through enteral feeding tubes (EFTs) in order to minimize efficacy and safety
problems. MATERIAL AND METHODS: The study was performed in a public secondary
care hospital with level II accreditation by the National Accreditation
Organization (Organizacao Nacional de Acreditacao ONA), in Fortaleza, Ceara,
north-eastern Brazil. RESULTS: One hundred and eight oral solid medications that
could be administered through EFTs and were not available in liquid forms were
evaluated via transformation of their solid dosage forms into liquid forms.
Dispersion times and conditions were assessed to determine which medications
should be crushed. We compared the use of dispensers and syringes and their
connections to enteral feeding tubes and intravenous devices. Medications whose
dispersion occurred within 20 minutes and could be visually perceived and whose
content could be expelled without occluding the oral syringe were considered
"satisfactory". CONCLUSIONS: The dispersion was "satisfactory" in 82 (75.9%) of
the medications; they were classified as capable of being dispersed in water in
the oral syringe for further administration via EFTs without the need for
crushing. Use the dispenser instead of the syringe for drug administration was
safer because the dispenser apparatus did not fit into equipment for intravenous
drug administration.
PMID- 28421777
TI - Quality control of enteral nutrition therapy in cancer patients at nutritional
risk.
AB - INTRODUCTION: Quality indicators in nutritional therapy (QINTs) allow for the
practical assessment of quality in the management of enteral nutrition therapy
(ENT) among hospitalized patients. OBJECTIVE: To control ENT quality in cancer
patients at nutritional risk. METHODS: A prospective, observational study was
performed with cancer patients over 19 years of age who had undergone exclusive
ENT for at least 72 h. Nutritional Risk Screening was used to assess nutritional
risk; in the presence of nutritional risk, the Subjective Global Assessment (SGA)
was used. Six QINTs were applied. RESULTS: Our study included 211 patients (mean
age: 59 +/- 10 years, 67.3% men). Most common cancer diagnoses were head and neck
(68.2%) and gastrointestinal (18%). Nutritional risk was identified in 93.3% (n =
197) of patients; SGA identified malnutrition in 84.2% of patients (n = 166). ENT
was used for 9.7 +/- 7 days, presenting a daily deficit of -243.1 +/- 141 ml of
dietary volume, -363.3 +/- 214.1 kcal, and -14.2 +/- 8.41 g of protein. Three of
the six QINTs were in accordance with the proposed goal: frequency of SGA
application, calculations of nutritional needs, and frequency of diarrhea. Three
of the six QINTs were in disagreement with the proposed goal: ENT infused volume
exceeding 70% of prescribed volume, frequency of digestive fasting exceeding 24
h, and frequency of constipation. Prescriptions for anticholinergic drugs (p =
0.023) and diuretics (p = 0.007) were associated with diarrhea. CONCLUSION:
Nutritional risk and malnutrition are frequent among ENT cancer patients. Quality
control in ENT was moderately impaired by episodes of fasting and intestinal
motility disorders.
PMID- 28421778
TI - Cost analysis of home parenteral nutrition in Spain
AB - Introduction: Home parenteral nutrition (HPN) improves quality of life, allowing
patients to receive nutrition at home and providing a social and labor
integration to these patients.Objective: To assess the direct costs of HPN in
adult population in Spain.Methods: A literature review of the records of HPN in
Spain, carry out by NADYA-SENPE Group (years 2007-2014), was performed. The
analysis included the evolution of: patients requiring HPN, number of
episodes/patient, mean duration of episodes, description of delivery routes and
complications rate. HPN consumption and cost were estimated. Patients were
grouped according to their pathological group: benign and malignant. Direct costs
(?, 2015) included were: parenteral nutrition bags, delivery sets and costs due
to complications.Results: The number of patients who receive HPN has increased
over years (2007: 133 patients; 2014: 220 patients). The average number of
episodes per patient ranged from 1-2 episodes per year. The average duration of
those episodes decreased (2007: 323 days; 2014: 202.8 days). Tunneled catheters
were the most used and septic complications were the most common. The average
annual cost per patient was estimated at ? 8,393.30 and ? 9,261.60 for benign and
malign disease respectively. Considering that 220 patients required HPN in 2014,
an annual cost of ? 1,846.524.96 (? 1,389,910.55 directly due to HPN) and ?
2,037,551.90 (? 1,580,937.50 directly due to HPN) was estimated for patients with
benign and malignant pathologies respectively. Conclusions: These results can be
used to develop future economic evaluations on HPN and to establish effi cient
prioritization strategies to allocate available resources.
PMID- 28421779
TI - Oral glutamine reduces myocardial damage after coronary revascularization under
cardiopulmonary bypass. A randomized clinical trial.
AB - BACKGROUND: Glutamine is the most abundant free amino acid in the body. It
modulates immune cell function and is an important energy substrate for cells in
critically ill patients. Reduction of injury cardiac markers had been observed in
patients receiving intravenous glutamine and in a pilot study with oral
glutamine. The aim of this study was to analyze the effect of preoperative oral
supplementation of glutamine on postoperative serum levels of cardiac injury
markers. METHODS: A randomized clinical trial was performed in 28 Mexican
patients with ischemic heart disease who underwent cardiopulmonary bypass with
extracorporeal circulation. Patients were randomly assigned to receive oral
glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury
markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were
measured at 1, 12, and 24 hours postoperatively. RESULTS: At 12 and 24 hours
serum markers levels were significantly lower in the glutamine group compared
with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001,
respectively). Overall, complications were significantly lower in the glutamine
group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2
cases of multiple organ failure in control group and 1 case of pulmonary embolism
in glutamine group (p = 0.50). CONCLUSION: Preoperative oral glutamine
standardized at a dose of 0.5 g/kg/day in our study group showed a significant
reduction in postoperative myocardial damage. Lower cardiac injury markers
levels, morbidity and mortality were observed in patients receiving glutamine.
PMID- 28421780
TI - Intestinal dysfunction in the critical trauma patients - An early and frequent
event.
AB - BACKGROUND: Small-bowel dysfunction exerts a relevant prognostic impact in the
critically ill patients. Citrullinemia has been used in the evaluation of the
intestinal function and it is considered an objective parameter of the functional
enterocyte mass. Present study proposes to determine the intestinal dysfunction
prevalence and the citrullinemia kinetic profile in severe trauma patients and to
investigate its correlation with severity indicators and clinical outcome.
METHODS: A prospective study including 23 critical trauma patients was performed.
Aminoacidemias were quantified, by ion exchange chromatography, at the admission
and at the first and third days. Severity and outcome parameters were registered.
RESULTS: In severe trauma patients, severe hypocitrullinemia (< 20 MUmol/L)
prevalence at admission was high (69.6%) and mean citrullinemia was low (19.5 +/-
11.1 MUmol/L). Baseline citrullinemia was inversely and significantly correlated
with shock index (r = -55.1%, p = 0.008) and extent of invasive ventilation
support (r = -42.7%, p = 0.042). Citrullinemia < 13.7 MUmol/L at admission,
observed in 17.4% of patients, was associated with higher shock index (1.27 +/-
0.10 versus 0.75 +/- 0.18, p = 0.0001) and longer duration of invasive
ventilation support (20.3 +/- 7 versus 11.2 +/- 7.1 days, p = 0.029) and
intensive care unit stay (22 +/- 5.9 versus 12.2 +/- 8.8 days, p = 0.048). A
citrullinemia decrease in the first day after admittance superior to 12.7%
constituted a significant predictive factor of in-hospital mortality (75 versus
14.3%, p = 0.044; odds ratio = 7.8; accuracy = 65.2%; specificity = 92.3%;
negative predictive value = 85.7%] and lower actuarial survival (69.8 +/- 41.6
versus 278.1 +/- 37.4 days, p = 0.034). CONCLUSIONS: Those results confirm the
high prevalence and the prognostic relevance of hypocitrullinemia, considered a
biomarker of enterocyte dysfunction, in severe trauma patients.
PMID- 28421781
TI - Contribution of bioavailable iron and zinc to the diet of Honduran children under
24 month
AB - Objective: In the present study we analyzed 18 baby food (10 made from
traditional Honduran recipes, and 8 industrial baby food sold in that country)
involving the staple food of Honduran excluded infants breast milk and infant
formulas. Material and methods: The content and bioaccesibility (soluble and
dialysable fractions) of Fe and Zn were determined. For thisin vitro
gastrointestinal digestion in a first phase of gastric digestion (pepsin)
followed by a second phase of intestinal digestion (with pancreatin and bile
salts) was simulated. The atomic absorption spectrometry mineral content measured
in soluble and dialyzable fractions. Results: Traditional porridges from Honduras
(PTH) showed low density of micronutrients being the PTH prepared based on "rice
with beans and greens", "rice with ground beans" and "beans with banana" which
had a higher content values of 1.96, 1.56, and 1.46 mg Fe/100 g, respectively,
although in vitroavailability values below 50% of its content. For Zn in these
recipes, the values found were very low being below the detection limit. In
relation to industrial porridges (PIH), those of "rice", "wheat with milk" and "5
cereals" they had a higher content of Fe (9.4, 8.53 and 7.56 mg Fe/100 g,
respectively). Its availability in vitro was greater than 70% in all cases. PIH
Zn showed values of 1.36, and 0.99 mg Zn/100 g samples of "wheat with milk" and
"wheat with honey", respectively, and increased availability of 75%. Conclusions:
It is shown that PTH have some limitations in its formulation that makes the
selected micronutrients are in fewer and even less bioaccessible, compared with
PIH, so review is recommended to avoid supplementation of these micronutrients
and help improve the nutritional status of the child population as Honduran model
country in Central America.
PMID- 28421782
TI - Breastfeeding for acute pain control on infants: a randomized controlled trial
AB - Objective: To determine the effectiveness of breastfeeding (BF) for the
management in acute pain after vaccination in infants under 6 months of age when
compared to the milk substitute (MS) and not to apply any maneuver. Methods: A
controlled, single-blind phase III clinical trial was conducted on infants under
6 months old to evaluate the effectiveness of BF in acute pain by vaccination.
Divided in 3 groups: BF, milk substitutes (MS), and without applying any
analgesic maneuver (control). Pain was measured by crying time and pediatric pain
scale. Statistical analysis was performed using the Kruskal Wallis and Mann
Whitney U for quantitative variables. For qualitative data, Chi2 was applied
Kaplan Meier was used to analyze the total time crying.Results: A total of 144
patients were recruited, divided in groups of 48 patients. The group of BF had
fewer crying time (p = 0.007) and pain rating at 90 (p = 0.006) and 120 (p =
0.003) seconds compared with other groups. There was no significant difference in
the crying time (p = 0.396) and the pain scale between the group receiving MR and
control.Conclusions: Breastfeeding is effective in management of acute pain by
vaccination in infants under six months of age compared to milk substitute and
control.
PMID- 28421783
TI - Factors associated with body mass index in Brazilian children: structural
equation model
AB - INTRODUCTION: Overweight and obesity in children is an important global problem.
Its prevalence is increasing in developed and developing countries. OBJECTIVE:
The aim of this study was to evaluate the association between socioeconomic
conditions, maternal body mass index (BMI), food security, and intake of
obesogenic foods on excess body weight in children. METHODS: A cross-sectional
study was conducted, using the data of 3,676 children from the latest National
Demographic and Health Survey in Brazil. The children's BMI was the study
outcome. Socioeconomic condition, maternal BMI, food security, and intake of
obesogenic foods were use as predictors. structural equation models were used for
analysis. RESULTS: Socioeconomic conditions directly influenced the children's
BMI (beta = 0.102; p = 0.02), mediated by intake of obesogenic foods (beta =
0.018; p = 0.04). A direct association was observed between maternal and child
BMIs (beta = 0.169; p < 0.001) and intake of obesogenic foods and child BMI (beta
= 0.114; p < 0.001). CONCLUSIONS: Favorable socioeconomic conditions, increased
maternal BMI, and intake of obesogenic foods contributed to increased child BMI.
PMID- 28421784
TI - Assessment of anthropometric indicators in children with cerebral palsy according
to the type of motor dysfunction and reference standard.
AB - AIM: The study aimed to demonstrate that the assessment of the anthropomorphic
measurements of children with cerebral palsy (CP) varies according to the type of
motor dysfunction and references standard used for comparison. METHOD: In a cross
sectional design, 108 children 2 to 16 years were classified according to the
type of motor dysfunction by gender and age group. Weight, mid-upper-arm
circumference (MUAC), and alternative measures for height were performed.
Height/age and weight/age indexes and BMI were evaluated with percentiles and/or
Z-scores with reference to a number of previously published references of growth,
including those of the World Health Organization (WHO). RESULTS: Fifty-three
(49.1%) were females and 55 (50.9%) males. Spastic type was predominant (73.1%)
and 26.9% were other types of dysfunction. Most of the children were located on
level IV (14.6%) and level V (73.1%) of the Gross Motor Function Classification
System (GMFCS). Significant differences were found, suggesting that weight (p =
0.002), height (p = 0.001), and MUAC (p = 0.05) are higher in the spastic group
than in other groups. CONCLUSIONS: The anthropometric indicators were
significantly higher in the spastic group than in other groups. Upper-arm length
(UAL) seemed less appropriate than knee height (KH) and lower-leg length (LLL)
for measuring height. The WHO reference standard was not useful to evaluate the
majority of anthropometric indexes in children with CP, other references as the
growth charts of Day and Brooks have been more suitable.
PMID- 28421785
TI - Association between vitamin D levels and cardiovascular risk factors in obese
children and adolescents.
AB - BACKGROUND AND AIM: Childhood obesity is associated with an increased risk of
chronic disease. We aimed to determine the association between vitamin D
deficiency and cardiovascular risks in obese children. METHOD: The studied
children were selected from obese children who were followed up at obesity
clinic, aged 6-17 years. Basic demographic information and laboratory data were
collected retrospectively from hospital records. RESULTS: A total of 310 students
(178 [57.4%] girls) were evaluated for 25-hydroxyvitamin D (25[OH] D) levels in
late winter/spring. The prevalence rates of vitamin D deficiency, insufficiency,
and sufficiency were 62.3%, 34.5%, and 3.2%, respectively. Insulin resistance was
observed in 146 (47.1%) children; the frequencies of dyslipidemia and
hypertension were 31% and 19.4%, respectively. The mean atherogenic dyslipidemia
ratio was higher in the deficient group (p = 0.049). Inverse correlations of
25(OH) D levels were observed with homeostasis model assessment of insulin
resistance values (r = -0.146, p = 0.010). The mean values of 25(OH) D (ng/mL)
were lower in girls (12.15 +/- 6.60) than in boys (16.48 +/- 8.69) (p < 0.05) and
in children with hypertension (11.92 +/- 5.48) than in those without (14.50 +/-
8.24) (p < 0.05). CONCLUSIONS: Vitamin D deficiency is observed more frequently
than expected in obese children and adolescents. Our findings indicate that low
25(OH) D levels are associated with insulin resistance. Vitamin D deficiency
could contribute to the morbidities associated with childhood obesity, such as
insulin resistance or diabetes mellitus, increased cardiovascular/cardiometabolic
risks, atherogenic dyslipidemia, and hypertension.
PMID- 28421786
TI - Infant growth and early adiposity depending on immigrant background and
anthropometric standards; the CALINA Study.
AB - OBJECTIVE: To compare infant growth and adiposity pattern up to 2 years of age in
Spanish infants, depending on maternal origin and anthropometric standards.
METHODS: Longitudinal study of a representative cohort of infants born at term in
Aragon (Spain) (n = 1.430). Mean z-scores of weight, length, body mass index,
triceps and subscapular skinfolds were calculated until 24 months of age using
World Health Organization (WHO), Euro-Growth and Spanish growth standards and
categorized by maternal origin (Spanish vs. immigrant). RESULTS: Infants of
immigrant mothers had higher weight, length, body mass index, triceps and
subscapular skinfolds than Spanish maternal origin infants during the first
months of life. Mean z-scores significantly varied depending on growth standards
used. At 18 months of age, all anthropometric differences between both groups
disappeared, but only when using WHO growth standards. Mean triceps and
subscapular skinfold z-scores substantially and progressively increased from 3
months to 24 months of age in both groups compared to WHO standards. At 24
months, the prevalence of infants at risk of overweight and overweight were
similar in both groups (Spanish: 15.1% and 3.8%; immigrant: 14.7% and 4.9%,
respectively). CONCLUSIONS: Infant growth, adiposity patterns and prevalence of
overweight depend on maternal origin, showing initial differences which
progressively disappeared at 24 months of life when WHO growth standards were
used. Differences in infant mean anthropometric measurements depend on
anthropometric standard used.
PMID- 28421787
TI - Adherence to the Mediterranean diet pattern, cognitive status and depressive
symptoms in an elderly non-institutionalized population.
AB - INTRODUCTION: Scientific evidence indicates that adherence to the Mediterranean
diet protects against the deterioration of cognitive status and depressive
symptoms during aging. However, few studies have been conducted in elderly non
institutionalized subjects. OBJECTIVE: This study evaluated the relation between
the adherence to the Mediterranean dietary pattern and cognitive status and
depressive symptoms in an elderly population over 75 years. METHODS: A cross
sectional study was conducted in a Mediterranean city (Garrucha, Spain) in 79
elderly people over 75 (36 men and 41 women). Adherence to the Mediterranean
dietary pattern was determined using the Mediterranean Diet Adherence Screener
(MEDAS). Cognitive function was determined by the Mini Mental State Examination
(MMSE), and depressive symptoms were assessed by the Geriatric Depression Scale
(GDS). RESULTS: Most of population showed a very high adherence to the
Mediterranean diet pattern and optimal cognitive and affective status. They
consumed olive oil as their main source of fat, high levels of fish and fruit,
low levels of foods with added sugars, and a low consumption of red meat. A
significant relation between the MEDAS and MMSE scores was found. However, no
relationship was observed between the MEDAS and GDS. CONCLUSIONS: The
Mediterranean diet pattern was positively related with the cognitive function,
although the infl uence of a healthy dietary pattern on the symptomatology of
depression was unclear. However, an effective strategy against cognitive function
and depression would be to improve physical activity rates, establish lifelong
healthy eating habits, and consume a nutritionally-rich diet in order to enhance
quality of life of the elderly.
PMID- 28421788
TI - Factors associated with sarcopenia in institutionalized elderly.
AB - INTRODUCTION: The sarcopenia is a negative aspect for the health of the elderly,
increased the risk for disease and mortality. Additionally can contributes
greatly to functional reducing capacity and quality of life. OBJECTIVE: To
identify the prevalence and factors associated with sarcopenia in
institutionalized elderly. METHODS: This is a cross-sectional study, conducted
with 216 elderly people, aged >= 60 years, of both sexes, residents in long-term
care facilities in Salvador-Bahia, Brazil. To identify sarcopenia was used the
skeletal muscle Index. Covariates were considered: gender, age, time of
institutionalization, type of institution, body mass index and functional
capacity. The Association between sarcopenia and covariates was evaluated using
the Poisson regression model with robust variance. RESULTS: The prevalence of
sarcopenia in the elderly was 72.2% and this condition was associated with male
sex (PR = 1,33; CI 95% = 1,081,65), thinness (PR = 1,29; CI 95% = 1,16-1,43) and
obesity (PR = 0,37; CI 95% = 0,23-0,61). CONCLUSION: The prevalence of sarcopenia
was high among the elderly living in long-term institutions, especially among
men. Elderly with thinness showed greater impairment of muscle reserves, while
the state of obesity was protective.
PMID- 28421789
TI - How does coconut oil affect cognitive performance in alzheimer patients?
AB - Introduction: Alzheimer's disease is one of the most prevalent neurodegenerative
dementia in developed world. This fact, coupled with the lack cure, makes new no
pharmacological therapeutic strategies such as nutrient management to
investigate. In this regard, it stresses the possible influence of coconut oil as
alternative energy source capable of stopping the progressively neuronal death
that occurs in this disease.Objectives: To assess the cognitive impact of coconut
oil in Alzheimer's patients, and specifically in orientation, language-building,
fixing, calculation-concentration and memory areas.Methods: Prospective,
longitudinal, qualitative, analytical and experimental study through a clinical
trial where 44 patients with Alzheimer's in region of Ribera (Valencia), of which
half was selected to receive during 21 days, 40 ml coconut oil daily divided
between breakfast (20 ml) and food (20 ml). Before and after administration of
the oil, they were evaluated through cognitive test Mini-Mental State Examination
to determine possible changes.Results: It was observed in patients who received
coconut oil, that cognitive improvement after completion of the intervention,
statistically significant improved in the orientation and language-construction
areas.Conclusions: Coconut oil appears to improve cognitive abilities of
Alzheimer's patients, with different intensity depending on the cognitive area.
PMID- 28421790
TI - Abdominal obesity is strongly associated to blood pressure in young Mexicans.
AB - OBJECTIVE: The objective of this study was to determine associations between
abdominal obesity (AOb) and the other components of metabolic syndrome (MetS) in
young Mexicans in a cross-sectional survey completed during a 4 year period.
METHODS: This cross-sectional study reports on components and prevalence of MetS
by using Alberti et al. (16) criteria, as well as association between AOb and
elevated blood pressure (BP) of 2,993 Mexican university students, ages 17 to 25
years (66% women) from central and northern Mexico, over a 4-year survey (2010
2013). RESULTS: The most prevalent MetS components in the total sample were low
HDL-C concentration (43.6%) and AOb (41.1%). MetS prevalence was 11.8%, more men
than women were classified with MetS (14.3% vs. 10.5%, p < 0.01). BP was the MetS
component with the lowest prevalence (8.6%). A strong association between AOb and
altered BP with in both men and women was found (OR 4.3, IC95% 2.5-7.4).
CONCLUSIONS: Even BP was the component with the lowest prevalence, AOb was more
strongly associated with it. This fact, could explain the prevalence of
hypertension among young Mexican adults.
PMID- 28421791
TI - Association of 4-hydroxynonenal with classical adipokines and insulin resistance
in a Chinese non-diabetic obese population.
AB - BACKGROUND: The prevalence of obesity is increasing worldwide. Oxidative stress
plays an etiological role in a variety of obesity-related metabolic disorders. 4
hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product
derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse
biological effects that are not well detailed. Obesity is associated with
decreased plasma adiponectin concentrations and increased production of lipid
peroxidation products, including 4-HNE, in adipose tissue. There may be some
association between the level of adipokines and 4-HNE. MATERIAL AND METHODS: To
analyze the associations between 4-HNE and classical adipokines, namely,
adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and
leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects
were determined by ELISA, and their associations with adiposity, glucose, lipid
profiles, insulin secretion and insulin sensitivity were studied. RESULTS: Plasma
4-HNE levels were significantly increased in patients with NDO compared with
healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and
positively correlated with leptin. The plasma levels of 4-HNE were significantly
correlated to several parameters involved in body mass index (BMI) and insulin
resistance (IR). The 4-HNE levels were positively correlated with BMI and
negatively correlated with insulin sensitivity. CONCLUSION: We conclude that 4
HNE is associated with the secretion of adiponectin and leptin and is correlated
with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE
in NDO patients, which supports the potential role of 4-HNE in the development of
obesity-related disorders.
PMID- 28421792
TI - Micronutrient supplementation in gastric bypass surgery: prospective study on
inflammation and iron metabolism in premenopausal women.
AB - BACKGROUND: Low-grade chronic inflammation in morbid obesity is associated with
impaired iron metabolism. Bariatric surgery is effective in weight loss; however,
it can induce specific nutritional deficiencies, such as iron, especially in
premenopausal women. Alternatively, after surgery, there is an improvement in
systemic inflammation, raising questions concerning the dosages of micronutrient
supplementation. OBJECTIVES: This study aimed to assess the effect of two
micronutrient supplementation schemes before and 6 months after a Roux-en-Y
gastric bypass (RYGB) surgery on inflammation and iron metabolism in
premenopausal women. METHODS: This prospective study included 45 premenopausal
women (aged 20-45 years; body mass index [BMI] >= 35 kg/m2) divided into two
supplementation schemes: group 1 (n = 34): daily supplemental dose of 1 RDA 30
days before surgery and 2 RDAs during the six months following surgery; and group
2 (n = 11): daily supplementation of 1 RDA during the 6 months postsurgery.
Anthropometry, dietary intake, inflammation, and iron metabolism were monitored.
RESULTS: Evident reductions in BMI, high-sensitivity C-reactive protein, and
ferritin levels for both groups occurred 6 months after surgery. Additionally,
anemia was 9% in both groups after surgery. However, group 1 exhibited an
increased transferrin saturation index and reduced transferrin levels.
Multivariate regression analysis suggested serum iron, hepcidin, and iron intake
determined ferritin values before and after RYGB surgery. CONCLUSION: Six months
after RYGB, systemic inflammation was reduced in both supplementation schemes.
However, supplementation of 1 RDA before and 2 RDAs after surgery resulted in
better improvements on iron metabolism.
PMID- 28421793
TI - Effects of a high-fat meal on postprandial incretin responses, appetite scores
and ad libitum energy intake in women with obesity.
AB - BACKGROUND: Considering the possible role of triglycerides (TG), glucose
dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in
the regulation of appetite, this study aimed to compare high fat meal-induced
response of GIP and GLP-1, appetite scores and ad libitum energy intake in women
with obesity, according to postprandial increment in triglyceridemia (?TG).
Methods: Thirty-three no-diabetic women (BMI = 35.0 +/- 3.2 kg.m-2) were divided
into two groups: Group with ?TG <= median were called "Low TG change -LTG" and
?TG > median, "High TG change - HTG". Plasma concentrations of GIP, GLP-1 and
appetite sensations were measured prior to, and every 30 min for 180 min after
ingestion of a high-fat breakfast. An ad libitum lunch was served 3 h after the
test meal. RESULTS: The AUC incrementalGIP were significant lower in HTG vs. LTG
group (p = 0.03). The same was observed for GIP levels at 150 min (p = 0.03) and
at 180 min (p < 0.01). Satiety was lower in HTG at 120 min (p = 0.03) and 150 min
(p < 0.01). The AUC totalGLP1 were similar between groups and there were no
between-group differences for the GLP-1 at each time point. Ad libitum food
intake were also similar between groups. CONCLUSIONS: The HTG group exhibited
differences in satiety scores and lower postprandial secretion of GIP, however
with no impact on ad libitum food intake in short term.
PMID- 28421794
TI - Relation of Trp64Arg polymorphism of beta 3 adrenoreceptor gene with metabolic
syndrome and insulin resistance in obese women.
AB - BACKGROUND AND AIM: Trp64Arg variant in beta 3 adrenoreceptor has been reported
to be associated with increased body weight and insulin resistance. These risk
factors are the ones that make up the so-called metabolic syndrome. The aim of
our study was to investigate the relationship between metabolic syndrome and
Trp64Arg polymorphism in the beta3 adrenoreceptor gene in obese women. METHODS: A
population of 531 obese women was analyzed in cross-sectional survey. A
bioimpedance, blood pressure, a serial assessment of nutritional intake with 3
days written food records and biochemical analysis were performed. Genotype of
beta 3 adrenoreceptor gene polymorphism (Trp64Arg) was studied. RESULTS:
Prevalence of metabolic syndrome (MS) with ATP III definition was 47.1% (250
patients) and 52.9% patients without MS (n = 281 patients). Prevalence of beta 3
genotypes was similar in patients with metabolic syndrome (87.6% wild genotype
and 12.4% mutant genotype) and without metabolic syndrome (87.9% wild genotype
and 12.1% mutant genotype). Insulin and HOMA levels were higher in patients with
mutant genotype than wild type, in patients with and without metabolic syndrome.
CONCLUSION: In mutant group of beta3 adrenoreceptor gene patients have higher
insulin and HOMA levels than wild type group, without relation with metabolic
syndrome.
PMID- 28421795
TI - BMI, BMIfat, BAI or BAIFels - Which is the best adiposity index for the detection
of excess weight?
AB - OBJECTIVE: To compare the diagnostic performance of adiposity indeces body mass
index (BMI), body mass index adjusted for fat mass (BMIfat), body adiposity index
(BAI) and body adiposity index for the Fels Longitudinal Study sample (BAIFels)
and the overweight detection in a sample of the Brazilian population. METHODS:
Cross-sectional study with 501 individuals (female/male = 387/114), which
underwent anthropometric measurements and body composition for subsequent
calculation of adiposity indices. Statistical analyzes considered p < 0.05 as
statistically significant. RESULTS: The averages were: age of 46.94 +/- 14.22
years and 48.05 +/- 14.40 years, weight 79.5 +/- 16, 14 kg and 70.42 +/- 16,62
kg, height 172.86 +/- 7.6 cm and 159.0 +/- 7,35 cm, for men and women,
respectively. According to the eutrophic ratings and overweight, the BMIfat
ranked 40.3% and 34.0% for men and 21.7% and 65.0% for females, r espectively.
While the BAI held 47.7% and 62.3% for men and 65.6% and 34.4% for women,
respectively. The receiver operating characteristic (ROC) curve of BMIfat was
clearly superior to all other indexes for both men (93.1%) and women (97.8%),
respectively. CONCLUSION: Findings suggest that BMIfat is the index that has
better relationship with the prediction of body fat, BAI did not exceed the
limitations of BMI. Future studies should seek to expand this study by adopting
the gold standard methods such as DXA and it is necessary to extend the
investigation of the validity of adiposity indices to different ethnic groups.
PMID- 28421796
TI - Effect of satiety on body composition and anxiety in university athletes: cohort
study.
AB - BACKGROUND: Satiety is a determining parameter in nutrient intake control, which
in the long run impacts on body weight. Many athletes need strict control on
their weight to achieve their aims of the season. AIM: The aim of this study is
to analyse the influence of satiety on body weight control and competitive
anxiety in a university athletes population when they ingest ad libitum foods
(SATIETY), or follow a nutritional dietary programme (DIET). METHODS: The present
study was a cohort study, in which 40 male university athletes participated. The
assessment of body weight was done using the ISAK recommendations in its limited
profile. The study of competitive anxiety was evaluated using the CSAI-2
questionnaire. RESULTS: Results showed that the DIET group decreased
significantly their body weight compared to the SATIETY group, they also obtained
a significant improvement in their body composition, reducing fat mass. The
SATIETY group didn't show significant reductions in fat mass. This group showed
higher competitive anxiety values than the DIET group. CONCLUSIONS: The
university athletes that follow an adapted and individualized diet seem to show
improvements in their body composition and anxiety compared to those with ad
libitum food.
PMID- 28421797
TI - Malnutrition in hospitalized patients: results from La Rioja.
AB - BACKGROUND: There is a high malnutrition prevalence in hospitalized patients.
AIM: To determine the malnutrition prevalence in hospitalized patients of La
Rioja Community (Spain) when evaluated with different screening/ evaluation tools
and its relationship with hospital stay and mortality. METHODS: Cross sectional
observational study of hospitalized adult patients (age > 18 years old) from
medical and surgical departments that underwent within 72 h of their admission a
nutritional screening with Malnutrition Universal Screening Tool (MUST),
Nutritional Risk Screening (NRS) 2002, Controlling Nutritional Status (CONUT) y
Subjective Global Assessment (SGA). RESULTS: 384 patients (273 medical and 111
surgical) were evaluated. Almost fifty percent of them were considered
malnourished independently of the screening/assessment tool used. High
concordance was found between SGA and NRS-2002 (k = 0.758). Malnourished patients
had a longer hospital stay than those well-nourished (9.29 vs. 7.10 days; p =
0.002), used a greater number of medicines (9.2 vs. 7.4; p = 0.001) and underwent
a higher number of diagnostic tests (16.4 vs. 12.5; p = 0,002). CONCLUSIONS: Half
of the hospitalized patients in the medical and surgical department of La Rioja
are malnourished. This is associated with a longer hospital stay, higher use of
medicines, diagnostics tests and greater mortality. Malnutrition could be
detected with easy screening tools to treat it appropriately.
PMID- 28421798
TI - Assessment of individual carotenoid and vitamin A dietary intake in overweight
and obese Dominican subjects.
AB - INTRODUCTION: Carotenoids are plant pigment with important biological activities
in humans, such as provitamin-A among others. At present, there are no individual
carotenoid intake data in the Dominican population, which is at risk of vitamin A
deficiency and has an important percentage of overweight and obese individuals .
OBJECTIVE: To assess the individual components of vitamin A intake (retinol,
alpha-carotene, beta-carotene and beta-cryptoxanthin) and that of other relevant
dietary carotenoids like lutein, zeaxanthin and lycopene of Dominican daily food
intake. METHODS: Fifty overweigth and obese subjects (22-69 y). Individual
carotenoid intake, from whole diet and from the ingestion of fruits and
vegetables, was determined using three 24 h diet recalls and a specific
carotenoid database. Retinol, macronutrient and energy intake were calculated
using DIAL(r) software. RESULTS: The total carotenoid intake was 6363.2 ug/day,
56. 1% corresponding to provitamin A carotenoids (74.3% beta-carotene). Vitamin A
intake was supplied by retinol (40%) and by provitamin A carotenoids (60%);
vegetables contributed more than fruits (39.2% and 19.2%, respectively). Non
provitamin A carotenoid intake represents 43.9% of the total intake and is
supplied by lycopene and lutein plus zeaxanthin in similar percentages (52.3% and
47.7%, respectively). CONCLUSIONS: The diet of these Dominican subjets met the
recommended vitamin A intake, when expressed as retinol equivalents, 59% of which
was supplied by provitamin-A carotenoids from plant sources, mainly by red/orange
and white/yellow foods. Individual carotenoid intake is an aspect of great
interest for issuing dietary recommendations in the public health setting.
PMID- 28421799
TI - Antihypertensive effect of fermented skim camel (Camelus dromedarius) milk on
spontaneously hypertensive rats.
AB - BACKGROUND: Hypertension is one of the most common diseases in worldwide, thus
prevention of hypertension is important in reducing the risks of cardiovascular
disease. Milk contains bioactive peptides released during milk fermentation which
lead to exhibit angiotensin I converting enzyme (ACE) inhibitory. OBJECTIVE: The
aim of this study was to investigate the antihypertensive effect of fermented
skim camel milk on rats and compared with unfermented skim camel milk as control.
METHODS: The antihypertensive effect of fermented skim camel milk on thirty six
male spontaneously hypertensive rats (SHR) was carried out for (short-term) and
(long-term) using different doses (80, 240 and 1200 mg/kg body weight).
Angiotensin converting enzyme (ACE) activity was also measured using ACE Kit.
RESULTS: The blood pressure (systolic and diastolic) of spontaneously
hypertensive rats (SHR) in short term administration (24 hours) of 1200 mg/kg
body weight fermented skim camel milk decreased significantly (p < 0.05) from 22
to 36 mmHg and 28 to 32 mmHg, respectively, at four and eight hour of post
administration. On the other hand, the blood pressure of fermented skim camel
milk for long-term (20 days) decreased and affected the heart rate (beats/min).
The lowest record of systolic (41 mmHg) and diastolic blood pressure (19 mmHg)
were at dose of 1200 mg/kg body weight of fermented skim camel milk at 15 days of
administration. Likewise, ACE activity in plasma of SHR administered fermented
skim camel milk decreased significantly (p < 0.05) compared with the control
group. CONCLUSION: The hypotensive effect of fermented skim camel milk by L.
helveticus and S. thermophillus in SHR rats depends on the high dose of fermented
skim camel milk in short and long-term. The ACE activity inhibitory was clear
with fermented skim camel milk.
PMID- 28421800
TI - Prevalence and associated factors of sugar-sweetened beverages intake among
schoolchildren aged 9 to 17 years from Bogota, Colombia: the FUPRECOL Study
AB - Objective: The aim of the present study was to describe the intake of sugar
sweetened beverages and to examine of associated factors among schoolchildren
from Bogota, Colombia.Methods: From a total of 8,136 schoolchildren and
adolescents (age 9-17.9 years) taking part in the FUPRECOL Study. Sugar-sweetened
beverages intake was based on intake from "regular soda", "drink tea" and/or
"concentrated juices". Body weigth, heigth, body mass index (BMI), waist
circumference, and percentage body fat by electrical bioimpedance analysis were
measured such as adiposity markers. Associated factors (sex, age, abdominal
obesity, BMI classification, mothers' and fathers' educational level and
nutritional status by "Krece plus" questionnaire), were collected by structured
questionnaire. Associations were established through a binary logistic
regression. Results: Of the subjects, 58.4% were women. According to sex, boys
response highest intake of "regular soda" daily/weekly frequency of the 70.9% and
21.0%, respectively, followed by "concentrated juices" (64.4% weekly vs.11.3%
daily). In both gender, the prevalence of abdominal obesity was higher in
schoolchildren that responded to intake "regular soda" (23.3%), "concentrated
juices" (13.2%) and "drink tea" daily (9.7%). Age [OR 1.15 (95%CI 1.03 to 1.28)],
mothers' [OR 1.30 (95%CI 1.03 to 1.65)], and fathers' [OR 1.34 (95%CI 1.01 to
1.79) low educational level and nutritional status [OR 2.60 (95%CI 2.09 to
3.25)], were associated with daily intake of "regular soda".Conclusion: Age,
parental education level and dietary patterns were associated with sugar
sweetened beverages in schoolchildren in Bogota, Colombia. We recommended
comprehensive interventions which are involved nutritional and educational
component among children and adolescents from Bogota, Colombia.
PMID- 28421801
TI - Attitudes of Chilean students from different socioeconomic levels at the
beginning of the implementation of the law governing the sale and advertising of
foods high in critical nutrients
AB - Background: On June 27th 2016 the law that regulates sale and advertising of
foods high in critical nutrients was implemented in Chile. This law regulates the
processed food packaging labelling of foods high in calories, saturated fats,
sugars and sodium.Objective: To determine 8-12 year old school children
attitudes, from different socioeconomic levels (SEL) and nutritional status,
toward the new food labelling law.Methods: A previously validated survey was
applied, adding questions regarding the new logos to be added on the packaging of
foods and beverages. A descriptive analysis of the variables being studied was
conducted and differences in relation to the SEL and nutritional status were
determined using the Chi2 test.Results: Statistically significant differences
were not observed for gender or city. Regarding the new logos, 87.3% of the
children from a medium to high SEL and 78.5% from low SEL indicated that they
liked to be informed about the contents of food (p < 0.01). Fifty-three per cent
from medium to high SEL and 48% from low SEL would stop buying the foods with
logos. Fourteen per cent to 22% will continue to consume sweet biscuits, sugary
drinks, chocolates and chips, without a difference in SEL. Children with a normal
nutritional status and medium to high SEL placed more importance on logos high in
calories, saturated fats and sodium, and children of low SEL on logos high in
sugar. Overweight or obese children from medium to high SEL considered all four
logos more important than children of low SEL.Discussion: These results will
facilitate educational and social marketing support to improve the understanding,
compliance and fulfillment of the law.
PMID- 28421802
TI - Psychological capital and its relationship with lifestyle of Mexican university
students
AB - Background: University students don't have a healthy lifestyle so it is necessary
to identify psychosocial variables that can increase it.Objective: To determine
the relationship between the psychological capital (CapPsi) and lifestyle (EV) of
Mexican university students.Method: A cross-sectional and correlational study was
carried out among 320 students of a public university. The sample was non
probabilistic by quotas. To assess the factors of CapPsi were used the General
Scale of Self-efficacy, the Scale of Hope for Adults, Questionnaire of
Resilience, the Life Orientation Test and; to assess the lifestyle was used the
Fantastic questionnaire.Results: The variables of the CapPsi correlated with the
healthy lifestyle; resilience (r = 0.505, p < 0.01); hope (r = 0.432, p < 0.01);
optimism (r = 0.412, p < 0.01); and self-efficacy (r = 0.400, p < 0.01). The 33.3
of the total variance of the lifestyle was explained by the CapPsi (R2 =
0.333).Conclusions: Based on the results, it is assumed that the CapPsi improve
lifestyle; however, further research is necessary to determine if the influence
of CapPsi is in the adoption and / or maintenance of healthy lifestyle and
identify how each one of its factors infl uences it particularly. The CapPsi has
a representative percentage of prediction of healthy lifestyle. It is necessary
that health promotion and prevention programs incorporate the approach of CapPsi
to achieve a healthy lifestyle in the university students.
PMID- 28421803
TI - Risk factors related with lifestyle in patients with musculoskeletal disorders
AB - Background: Musculoskeletal disorders (MSDs) encompass a series of debilitating
diseases with high incidence and prevalence, representing a high economic and
social cost. Prevention is crucial, so is of great interest to determine
modifiable risk factors, such as those related to lifestyle. Methods: A
descriptive cross-sectional study was performed in 91 patients selected by
systematic random sampling and were divided into three experimental groups
according to the cause and evolution of its MSD (neck pain, knee pain and back
pain). A biometric measurement, nutritional assessment, physical and occupational
activity, muscle balance and oxidative status was performed.Results: The female
is the most affected gender by the presence of musculoskeletal injuries such as
neck pain and back pain. Overall, most patients (67.4%) had normal weight,
overweight 24.41% and only 8.1% were obese type I. Patients with neck pain are
the group doing less physical activity and worse muscular balance present.
Oxidative stress was higher in patients with knee pain than in the other groups.
Regarding the consumed diet, differences between experimental groups on the
mineral content (Zn, Mn, Se and I) and vitamins (folate and ascorbic acid) are
observed. Conclusions: Cholecalciferol intake and vitamins A and D is less than
those recommended in all subjects, which promotes muscle disease. Folate intake
was below recommendations, increasing susceptibility to oxidative stress. Obesity
and oxidative stress related to the prevalence of the different types of MSDs
studied.
PMID- 28421804
TI - Composition and diversity of acaroids mites (Acari: Astigmata) community in the
stored rhizomatic traditional Chinese medicinal materials.
AB - OBJECTIVE: To investigate the species and breeding density of ac a roid mites in
the stored rhizomatic traditional Chinese medicinal materials in Anhui province,
China, in order to supply evidences for control and prevention of such species.
METHODS: The stored traditional Chinese medicinal materials of root-stock origins
were collected in 30 herb stores and warehouses in 17 cities across Anhui
province. Mites were collected by using Tullgren funnel and directicopy, and
identified under microscopy. RESULTS: Twenty-two species of acaroid mites,
belonging to 15 genera under 5 families, were identified from the total 47 stored
samples, in which Tyrophagus putrescentiae, Acarus farinae, Carpoglyphus lactis,
and Cologlyplus berlesei were predominant. CONCLUSION: Breeding density of
acaroid mites was high in the stored rhizomatic traditional Chinese medicinal
materials in Anhui province. This indicates that the traditional Chinese
medicinal herbs of root-stock origins in storage are seriously contaminated by
the acaroid mites, and such infestation should be positively controlled to reduce
the potential harm to public health.
PMID- 28421805
TI - Trematode Aspidogastrea found in the freshwater mussels in the Yangtze River
basin.
AB - OBJECTIVE: To investigate the prevalence of trematode Aspidogastrea in the
freshwater mussels in the Yangtze River basin within Anhui province, China.
METHODS: We initially harvested the freshwater mussels living in the Yangtze
River running through Anhui area, and labeled them with corresponding number.
Then the samples were dissected for isolating the flukes, which were identified
by conventional staining. RESULTS: Infection rate of trematode Aspidogastrea in
freshwater mussels in the Yangtze River basin within the territory of Anhui
province was 30.38% (103/339) in general, and a total of 912 flukes of
Aspidogastrea were detected in the 103 mussels, with average infection rate of
8.85 for each mussel. CONCLUSION: Trematode Aspidogastrea is prevalent in the
freshwater bivalves living in the Yangtze River basin running through Anhui area,
and the treamatode was identified as Aspidogaster sp. belong to Aspidogaste under
Aspidogastridae of Aspidogastrea.
PMID- 28421806
TI - Diet and liver apoptosis in rats: a particular metabolic pathway.
AB - INTRODUCTION: Various studies have indicated an association between modifi cation
in dietary macronutrient composition and liver apoptosis. OBJECTIVE: To explain
how changes in metabolic pathways associated with a high-protein, high-fat, and
low-carbohydrate diet causes liver apoptosis. METHODS: Two groups of rats were
compared. An experimental diet group (n = 8) using a high-protein (59.46%), high
fat (31.77%), and low-carbohydrate (8.77%) diet versus a control one (n = 9) with
American Institute of Nutrition (AIN)-93-M diet. Animals were sacrificed after
eight weeks, the adipose tissue weighed, the liver removed for flow cytometry
analysis, and blood collected to measure glucose, insulin, glucagon, IL-6, TNF,
triglycerides, malondialdehyde, and beta-hydroxybutyrate. Statistical analysis
was carried out using the unpaired and parametric Student's t-test and Pearson's
correlation coeffi ents. Significance was set at p < 0.05. RESULTS: Animals from
the experimental group presented less adipose tissue than dose of the control
group. Percentage of nonviable hepatocytes in the experimental group was 2.18
times larger than the control group (p = 0.001). No statistically significant
differences were found in capillary glucose, insulin, glucagon, IL-6, or TNF
alpha between two groups. Plasmatic beta-hydroxybutyrate and malondialdehyde of
the experimental group expressed higher levels and triglycerides lower levels
compared with the control group. The results show a positive and significant
correlation between the percentage of nonviable hepatocytes and malondialdehyde
levels (p = 0.0217) and a statistically significant negative correlation with
triglycerides levels (p = 0.006). CONCLUSION: Results suggest that plasmatic
malondialdehyde and triglyceride levels are probably good predictors of liver
damage associated with an experimental low-carbohydrate diet in rats.
PMID- 28421807
TI - The antioxidants in the process of ocular pathology
AB - Introduction: The influence of antioxidants on ocular processes has taken on a
significant importance in recent years for its effects on visual health.
Oxidative stress is a factor involved in the development of major pathologies
such as cataracts, glaucoma and age-related macular degeneration (AMD).Objective:
To establish the scientific evidence that exists about the different types of
antioxidants and their effects on ocular pathological processes through a
systematic review.Methods: Literature search in MEDLINE, Scielo and Cochrane for
studies evaluating the use of antioxidants in the prevention and/or treatment of
eye diseases. Selected randomized controlled clinical trials over the past 7
years were selected.Results: The relationship between different types of
antioxidants, vitamin E, C, beta carotene, zinc, lutein, anthocyanins and
carotenoids, suggests a positive relationship with the risk and progression of
AMD and glaucoma parameters, indicating a lower risk of the disease due to an
increased consumption of antioxidants in the diet. Initial reports suggest a
potential role for diet modification in the treatment of age-related macular
degeneration and glaucoma primarily, not evidencing for the prevention of
cataract.Conclusions: Promoting adequate consumption of antioxidants in the diet
can prevent and protect against highly prevalent eye diseases. The antioxidants
of the group of vitamins are the most studied so far in the ocular pathologies.
More clinical trials are needed to establish these relationships more precisely.
PMID- 28421808
TI - Body-image dissatisfaction in children and adolescents: a systematic review
AB - Background: The difference in the perception between the perceived silhouette and
the desired silhouette has been defined as body image dissatisfaction
(BID).Objective: To review the type of methods for measuring BID, the frequency
of BID among children and adolescents.Method: We searched studies through
electronic databases (PubMed, Scielo and EBSCOhost), from cross-sectional studies
published in English or Spanish. Eligible studies assessing BID in children and
adolescents published in Spanish and English, from April 2010 to April 2015. Age,
sex, weight and method or scale used to evaluate the BID and the self- perception
of body weight were assessed.Results: Sixteen studies met the inclusion criteria,
and included children and adolescents aged 5 to 19 years. Nine types of
measurement methods of BID were found. In most of the studies, temporal stability
and validity test were performed. In BID studies where frequency was reported,
ranged from 44% to 83% for overweight or obese and 1.7% a 37% for underweight. In
some studies, BID was associated with age and was more frequent among girls. BID
was also present in thin boys.Conclusion: BID was more frequent among girls and
was positively associated with BMI. Despite the variety of methods used, the
results are consistent.
PMID- 28421809
TI - Recommended energy and nutrients intakes in the European Union: 2008-2016
AB - The aim of this document is to refl ect the changes happened in the European
Union legislation and the opinions of the European Food Safety Authority in
relation to the nutritional labeling on food, the reference values for energy,
macronutrients and micronutrients, and the tolerable upper safe levels.The
European legislation in force uses the labeling reference values established by
the Scientific Committee on Food in 2003. There would be advisable an update of
them from the reference values for vitamins and minerals established by the
European Food Safety Authority. Equally, there would be good to include reference
labeling values for polyunsaturated fatty acids, dietary fiber and choline, and
specific reference labeling values for children from 6 to 36 months.For vitamins
and minerals there would be desirable the revision of tolerable upper safe levels
and the establishment of maximum amounts allowed in fortified food and food
supplements in the European Union; its absence might represent a risk in some
population groups for an excessive and unsafe intake of certain minerals and
vitamins.
PMID- 28421810
TI - Catheter traction and gastric outlet obstruction: a repeated complication of
using a Foley catheter for gastrostomy tube replacement.
AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a safe procedure and
major morbidity is unusual. However, the number of PEG fed patients is increasing
all over the world and complications may become more and more frequent. CASE
REPORT: We describe a 73 years old woman with persistent vomit after replacement
of the standard PEG tube with a Foley catheter. An upper GI endoscopy showed the
catheter pulled into the duodenum causing gastric outlet obstruction. It was
removed and replaced by a suitable standard PEG tube, allowing PEG feeding to be
resumed. DISCUSSION: Previous reports pointed the risk of this complication,
almost always associated with insertion of a Foley-type catheter. Replacement of
PEG tubes should be performed by experienced teams using standard PEG tubes and
the use of Foley-type catheters for this purpose should be banned from routine
practice.
PMID- 28421811
TI - Characterization of Ornithobacterium rhinotracheale field isolates from Hungary.
AB - Ornithobacterium rhinotracheale is a widely distributed rod-shaped Gram-negative
bacterium that infects several avian species including chickens and turkeys. It
is associated with respiratory signs, growth retardation, mortality, and reduced
egg production, thus causing severe economic losses to the poultry industries. In
this study, 37 field isolates of O. rhinotracheale, collected from various
locations in Hungary between 1997 and 2015, were identified and characterized by
the analysis of partial 16S rRNA gene sequences, enterobacterial repetitive
intergenic consensus (ERIC)-PCR, and random amplified polymorphic DNA (RAPD) PCR
assays with the OPG11, OPH19, and M13 primers. Most of the field isolates were
serotype A, one was serotype B, and four were serotype D. One isolate could not
be typed with antisera against serotypes A-E. In a phylogenetic analysis of the
16S rRNA sequences, the isolates formed two clusters. Thirteen distinct patterns
were identified with ERIC-PCR, and the RAPD assay with the M13 primer assigned
the isolates to 10 different patterns. The other two RAPD assays were unsuitable
for distinguishing and grouping the isolates. Neither ERIC type nor RAPD pattern
correlated with the place or year of isolation. However, the strains isolated
from chickens were more heterogeneous on ERIC-PCR than the isolates recovered
from turkeys. In this study, ERIC-PCR was the most discriminatory method for
investigating the genetic diversity of O. rhinotracheale isolates.
PMID- 28421812
TI - Frequency of Incidental Findings and Subsequent Evaluation in Low-Dose Computed
Tomographic Scans for Lung Cancer Screening.
AB - RATIONALE: The U.S. Preventive Services Task Force recommends lung cancer
screening with low-dose chest computed tomographic scans (LDCT) for a well
defined high-risk population. Data on the frequency and impact of incidental
findings (IFs) based on LDCT scans performed within a centralized lung cancer
screening program have not been reported. OBJECTIVES: Researchers in previous
studies have reported IFs in the setting of clinical trials. We present our
findings in a real clinical setting where the decision to manage these findings
may depend on factors that are not captured in a research trial such as
disclosing IFs, patient preferences, severity of comorbidities, and physician
expertise. METHODS: We conducted a retrospective chart review of participants in
the Cleveland Clinic Lung Cancer Screening Program from April 1, 2015, to
February 17, 2016. Lung Imaging Reporting and Data System categories and all
reported findings were extracted from the structured radiology report. Downstream
investigations that occurred as a result of the imaging findings were recorded.
Medicare reimbursement rates were documented for all screening-related testing
and treatment. RESULTS: A total of 320 LDCT-screened patients' records were
reviewed. The most commonly reported IFs were pulmonary (69.6%), cardiovascular
(67.5%), and gastrointestinal (25.9%). Fifteen percent of the scans had an IF
that resulted in further evaluation. The majority of patients who underwent
further testing had cardiovascular findings (10.3%); less frequently, they had
thyroid or adrenal nodules (2.1%), hepatic lesions (0.9%), renal masses (0.6%),
or pulmonary disease (0.6%). The most frequently ordered investigations were
echocardiography (n = 9), cardiac stress test (n = 9), and CT angiography (n =
6). Reimbursement for the screening process, evaluation, and treatment of
screening-detected findings averaged $817 per screened patient. CONCLUSIONS:
Clinically significant IFs on LDCT scans for lung cancer screening are common,
and their potential impact should be included in the shared decision-making
process. Screening program staff should develop a standard approach for the
evaluation of these findings and consider the financial impact when seeking
infrastructure support for screening program implementation.
PMID- 28421814
TI - Elevated Monocyte to High-Density Lipoprotein Cholesterol Ratio and Endothelial
Dysfunction in Behcet Disease.
AB - Behcet disease (BD) is a multisystemic disorder characterized by endothelial
dysfunction and inflammation. Monocyte to high-density lipoprotein cholesterol
ratio (MHR) is a recently emerged indicator of inflammation and oxidative stress.
Sixty patients with BD and 50 control individuals were included to investigate
the relationship between MHR and endothelial dysfunction. Endothelial function
was assessed by flow- and nitroglycerin-mediated dilatation technique (FMD and
NMD, respectively). Serum high-sensitivity C-reactive protein (hsCRP) levels were
measured in all study participants. The MHR and hsCRP levels were significantly
higher in patients with active BD than in controls. Brachial artery FMD was
significantly lower in patients with active BD than in controls. Brachial artery
NMD was similar between groups. There was a strong inverse correlation between
MHR and FMD and a strong positive correlation between MHR and serum hsCRP levels.
Thus, elevated MHR may be a useful marker reflecting impaired endothelial
function and systemic inflammation in patients with BD.
PMID- 28421813
TI - Hemin Causes Lung Microvascular Endothelial Barrier Dysfunction by Necroptotic
Cell Death.
AB - Hemin, the oxidized prosthetic moiety of hemoglobin, has been implicated in the
pathogenesis of acute chest syndrome in patients with sickle cell disease by
virtue of its endothelial-activating properties. In this study, we examined
whether hemin can cause lung microvascular endothelial barrier dysfunction. By
assessing transendothelial resistance using electrical cell impedance sensing,
and by directly measuring trans-monolayer fluorescein isothiocyanate-dextran
flux, we found that hemin does cause endothelial barrier dysfunction in a
concentration-dependent manner. Pretreatment with either a Toll-like receptor 4
inhibitor, TAK-242, or an antioxidant, N-acetylcysteine, abrogated this effect.
Increased monolayer permeability was found to be associated with programmed cell
death by necroptosis, as evidenced by Trypan blue staining, terminal
deoxynucleotidyl transferase dUTP nick-end labeling assay, Western blotting for
activated forms of key effectors of cell death pathways, and studies utilizing
specific inhibitors of necroptosis and apoptosis. Further studies examining the
role of endothelial cell necroptosis in promoting noncardiogenic pulmonary edema
during acute chest syndrome are warranted and may open a new avenue of potential
treatments for this devastating disease.
PMID- 28421815
TI - Cross-protection conferred by immunization with an rOmpH-based intranasal fowl
cholera vaccine.
AB - A previous study demonstrated that a recombinant outer membrane protein H (rOmpH)
based intranasal fowl cholera vaccine elicited efficient homologous protection
against the Pasteurella multocida strain X-73 (A:1) in chickens. The present
study aimed to determine the cross-protectivity against heterologous P. multocida
strains. The rOmpH was purified via electroelution and formulated with two kinds
of adjuvants. The vaccine formulations in a total volume of 100 ul were 100 ug
rOmpH with 3 ug of Escherichia coli enterotoxin B or 10 ug of CpG ODN2007.
Chickens were assigned to three experimental groups depending on bacterial strain
challenge exposure as well as three control groups. The chickens were immunized
intranasally three times at three-week intervals. Challenge exposures were
conducted by inoculation with homologous strain X-73 or heterologous strains P
1059 (A:3) or P-1662 (A:4) at four weeks after the final immunization. The
specific antibody against rOmpH was produced in vaccinated birds. Sera IgY and
secretory IgA antibody titres were significantly increased (P < 0.05) post
immunization. The stimulation index values of the vaccinated groups were
significantly different from stimulation index values of the non-vaccinated
groups (P < 0.05). Chicken survival rates after exposure to avian P. multocida
strains ranged from 70% to 100%. There was no significant difference in
protection between two kinds of adjuvants in vaccine formulations. Statistical
analysis indicated no significant differences in protection among avian P.
multocida strains challenge exposure. We conclude that an in-house rOmpH-based
intranasal fowl cholera vaccine produced efficient cross-protectivity against
heterologous strains of P. multocida.
PMID- 28421816
TI - Cytotoxic steroid derivatives from the Vietnamese soft coral Sinularia brassica.
AB - Using various chromatographic separations, six ergostane-type steroids, including
one new compound sinubrassione (1), and two pregnene-type steroid glycosides,
including one new compound sinubrassioside (7), were isolated from methanol
extract of the Vietnamese soft coral Sinularia brassica. The structure
elucidation was confirmed by spectroscopic methods including 1D, 2D NMR and HR
ESI-MS. The cytotoxic activities of all the isolated compounds against three
human cancer cell lines were also evaluated using MTT-based colorimetric assays.
PMID- 28421817
TI - Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after
Whole-Lung Lavage for Pulmonary Alveolar Proteinosis. A Report of Five
Intractable Cases.
AB - Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized
by the excessive accumulation of surfactant proteins within the alveolar spaces
and by higher titers of autoantibodies to granulocyte-macrophage colony
stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The
antibodies inhibit the maturation and phagocytosis of alveolar macrophages.
Although the standard therapy for aPAP has been whole-lung lavage (WLL), this
procedure is invasive and needs to be repeated for several years. GM-CSF
inhalation therapy is a new procedure for treating aPAP and can induce remission
with less invasiveness, although it is generally less effective in severe cases.
We evaluated five cases with remarkable improvement by using sequential GM-CSF
inhalation therapy after WLL; however, the treatment failed when this therapy
preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the
efficiency of WLL in patients with severe aPAP.
PMID- 28421818
TI - Cell Origin Dictates Programming of Resident versus Recruited Macrophages during
Acute Lung Injury.
AB - Two populations of alveolar macrophages (AMs) coexist in the inflamed lung:
resident AMs that arise during embryogenesis, and recruited AMs that originate
postnatally from circulating monocytes. The objective of this study was to
determine whether origin or environment dictates the transcriptional, metabolic,
and functional programming of these two ontologically distinct populations over
the time course of acute inflammation. RNA sequencing demonstrated marked
transcriptional differences between resident and recruited AMs affecting three
main areas: proliferation, inflammatory signaling, and metabolism. Functional
assays and metabolomic studies confirmed these differences and demonstrated that
resident AMs proliferate locally and are governed by increased tricarboxylic acid
cycle and amino acid metabolism. Conversely, recruited AMs produce inflammatory
cytokines in association with increased glycolytic and arginine metabolism.
Collectively, the data show that even though they coexist in the same
environment, inflammatory macrophage subsets have distinct immunometabolic
programs and perform specialized functions during inflammation that are
associated with their cellular origin.
PMID- 28421820
TI - Characteristics associated with physical activity capacity and performance in
children and adolescents with an acquired brain injury.
AB - AIM: To examine characteristics associated with physical activity capacity and
performance in children with acquired brain injury (ABI). METHODS: 58 children
(32 men; age 11 years 11 months +/- 2 years 6 months; Gross motor function
classification system [GMFCS] equivalent I = 29, II = 29) >12 months post ABI
were recruited. Physical activity capacity measures included: (i) combined score
of three 30-second repetition maximum functional strength exercises; (ii) timed
up and go; (iii) 6-minute walk test and (iv) high-level mobility assessment tool
(HiMAT). Physical activity performance determined time spent in sedentary, light
and moderate to vigorous physical activity (MVPA). Full scale intelligence
quotient (FSIQ) was assessed using the Wechsler intelligence scale for Children
IV. Regression models were constructed with functional strength score (n = 56),
activity counts/minutes and time spent in MVPA and sedentary (n = 37). RESULTS:
The HiMAT and FSIQ explained 69% of the variance in functional strength. Age
explained 12% of the variance in counts/min and 14% of the variance in time spent
sedentary. GMFCS explained 10% of the variance in time spent in MVPA.
CONCLUSIONS: The ability to perform functional strength exercises is associated
with mobility beyond independence and adequate intellectual ability for children
with ABI. Age was the most significant factor associated with physical activity
performance, and interventions should target adolescents with ABI.
PMID- 28421819
TI - IL-4 Induces IL17Rb Gene Transcription in Monocytic Cells with Coordinate
Autocrine IL-25 Signaling.
AB - IL-25 and IL-4 signaling in the setting of infection or allergic responses can
drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to
mediate signaling through nuclear factor kappa B (NF-kappaB) transcriptional
activation. Despite the known coexistence of these two cytokines in the Type 2
inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes
is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb
protein in human lung tissue culture, primary alveolar macrophages, and the THP-1
monocytic cell line. IL-4 treatment triggers gene transcription for both IL-25
and IL-17Rb but does not alter the receptor mRNA stability. Genetic antagonism of
the IL-4 second messenger, signal transducer and activator of transcription 6
(STAT6), with small interfering RNA (siRNA) blunts IL-17Rb mRNA induction by IL
4. IL-25 induces signaling through the canonical NF-kappaB pathway, and STAT6 or
NF-kappaB signaling inhibitors prevent IL-17Rb expression. Blockade of IL-25 with
monoclonal antibody suppresses NF-kappaB activation after IL-4 treatment, and IL
4-mediated induction of IL-17Rb is suppressed by IL-25 siRNA. IL-25 and IL-17Rb
promoter regions harbor putative NF-kappaB and STAT6 consensus sites, and
chromatin immunoprecipitation identified these transcription factors in complex
with the IL-17Rb 5' untranslated region. In bronchoalveolar lavage RNA
preparations, IL-25 and IL-17Rb mRNA transcripts are increased in asthmatics
compared with healthy control subjects, and IL-25 transcript abundance correlates
strongly with IL-4 mRNA levels. Thus, these results indicate that IL-4 signaling
up-regulates the IL-25 axis in human monocytic cells, and that IL-25 may provide
autocrine signals in monocytes and macrophages to sustain IL-17Rb expression and
predispose to alternative activation.
PMID- 28421821
TI - Modeling and dynamic simulation of astronaut's upper limb motions considering
counter torques generated by the space suit.
AB - Extravehicular activity (EVA) is an inevitable task for astronauts to maintain
proper functions of both the spacecraft and the space station. Both experimental
research in a microgravity simulator (e.g. neutral buoyancy tank, zero-g aircraft
or a drop tower/tube) and mathematical modeling were used to study EVA to provide
guidance for the training on Earth and task design in space. Modeling has become
more and more promising because of its efficiency. Based on the task analysis,
almost 90% of EVA activity is accomplished through upper limb motions. Therefore,
focusing on upper limb models of the body and space suit is valuable to this
effort. In previous modeling studies, some multi-rigid-body systems were
developed to simplify the human musculoskeletal system, and the space suit was
mostly considered as a part of the astronaut body. With the aim to improve the
reality of the models, we developed an astronauts' upper limb model, including a
torque model and a muscle-force model, with the counter torques from the space
suit being considered as a boundary condition. Inverse kinematics and the Maggi
Kane's method was applied to calculate the joint angles, joint torques and muscle
force given that the terminal trajectory of upper limb motion was known. Also, we
validated the muscle-force model using electromyogram (EMG) data collected in a
validation experiment. Muscle force calculated from our model presented a similar
trend with the EMG data, supporting the effectiveness and feasibility of the
muscle-force model we established, and also, partially validating the joint model
in kinematics aspect.
PMID- 28421822
TI - Deflation of a Rathke cleft cyst triggered rupture of a superior hypophyseal
artery aneurysm: a case report.
AB - A 57-year-old woman was diagnosed as a Rathke cleft cyst (RCC). Endoscopic
transsphenoidal surgery (TSS) was performed uneventfully. She developed
subarachnoid haemorrhage on postoperative day 3. The vessels adhered the cyst had
been pulled into the pituitary fossa, causing an aneurysm.
PMID- 28421823
TI - Tapia syndrome: an unusual complication following posterior cervical spine
surgery.
AB - Tapia syndrome, a rare complication of posterior cervical surgery, characterised
by concurrent paralyses of recurrent laryngeal branch of vagus and hypoglossal
cranial nerves, occurred in a patient after posterior cervical foraminotomies for
radiculopathy. We discuss hypothesised pathophysiology, and diagnostic,
therapeutic and avoidance strategies in relevance to prone neurosurgical
procedures.
PMID- 28421824
TI - Thrombosis of the draining vein causes intracranial haemorrhage in the natural
history of brain arteriovenous malformation: case report.
AB - Rupture of arteriovenous malformations (AVM) may be caused by venous outflow
restriction, but there is no radiographic evidence of this. We report a case
showing only a venous thrombus preceding intracranial haemorrhage from AVM. This
is the first evidence that venous thrombus results in AVM rupture in its natural
history.
PMID- 28421825
TI - Seizures in patients with acute pesticide intoxication, with a focus on
glufosinate ammonium.
AB - The incidence and clinical aspects of seizures remain to be elucidated in
patients with acute pesticide intoxication. The present study included subjects
who ingested pesticide with the intention of committing suicide and were treated
at Soonchunhyang University Hospital (Cheonan, Korea) between January 2011 and
December 2014. We analyzed the incidence and characterized the type and frequency
of seizure, from the medical records of 464 patients with acute pesticide
intoxication, according to the pesticide class. The effect of seizure on the
clinical outcome was assessed. The incidence of seizure was 31.5% in patients who
ingested glufosinate ammonium {2-amino-4-[hydroxyl (methyl) phosphinoyl]
butyrate; ammonium DL-homoalanin-4-yl (methyl) phosphinate}, followed by those
who ingested pyrethroid (5.9%) or glycine derivatives (5.4%). All of the seizures
developed between 12 and 24 h of pesticide ingestion and had ceased by 72 h after
seizure initiation, following treatment with antiseizure medication. Generalized
tonic-clonic seizures were the most commonly observed (85.7% of the cases).
Multivariable logistic regression analysis showed that the effect of seizure on
mortality was not statistically significant. In conclusion, glufosinate ammonium
herbicide is the most common seizurogenic pesticide class. Seizure itself was not
a risk factor for mortality in patients with acute glufosinate ammonium
intoxication.
PMID- 28421826
TI - 6-Gingerol improves testicular function in mice model of chronic ulcerative
colitis.
AB - The persistent inflammation and oxidative stress at the local site in ulcerative
colitis reportedly extend to the testes via systemic circulation resulting in
testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound
isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in
mice was investigated in this study. Chronic ulcerative colitis was induced in
mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles.
Each cycle consisted of 7 consecutive days of exposure to DSS-treated water
followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or
sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination
with DSS-treated water during the three cycles. SZ served as standard reference
drug for colitis in this study. 6G significantly prevented the incidence of
rectal bleeding, decrease in the body weight gain and colon mass index in DSS
exposed mice. 6G significantly prevented colitis-mediated decreases in
luteinizing hormone, follicle-stimulating hormone and testosterone and decreases
oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with
concomitant augmentation of antioxidant enzymes activities, sperm
characteristics, marker enzymes of testicular function and histoarchitecture in
DSS-exposed mice. 6G exerted protective influence against ulcerative colitis
induced testicular damage via mechanisms involving its antioxidant and anti
inflammatory properties.
PMID- 28421827
TI - Pediatric Nandina domestica ingestions reported to poison centers.
AB - Nandina domestica is grown as an ornamental plant in the United States but has
also been reported as an invasive plant in a number of states. Parts of the
plant, particularly the berries, contain cyanogenic glycosides that convert to
hydrogen cyanide when ingested. This investigation characterized N. domestica
ingestions involving patients of age 5 years and less reported to Texas poison
centers during 2000-2015. There were 875 total N. domestica ingestions. A
seasonal pattern was observed with the highest proportion of ingestions occurring
in March (18.5%) and April (14.7%). The patients were male in 55.0% of the cases;
40.8% of the patients were of age 1 and 37.0% of age 2. Berries were specifically
mentioned in 709 ingestions, of which 57.3% involved one berry and 28.5% an
unknown number of berries. The ingestion occurred at the patient's own residence
in 92.9% of the cases, and the patient was managed on site in 97.0%. The most
frequently reported clinical effects were vomiting (3.7%), abdominal pain (1.0%),
diarrhea (0.9%), and nausea (0.7%). In conclusion, N. domestica ingestions among
young children generally do not result in serious outcomes and can be managed
successfully outside of a healthcare facility.
PMID- 28421828
TI - Jasmonic acid changes the composition of essential oil isolated from narrow
leaved lavender propagated in in vitro cultures.
AB - The aim of the present study was to determine the effect of jasmonic acid added
to the culture medium on composition of Lavandula angustifolia essential oils.
The chemical composition was determined by gas chromatography coupled to mass
detector (GC/MS). The experiment was conducted with the use of MS medium
supplemented with increasing concentration of JA (0.2, 0.5, 1, 1.5 mg?dm-3). It
was found that the analysed essential oils varied in terms of chemical
composition depending on the content of JA in the medium. All obtained essential
oils were characterised by a high content of sigma-cadinene (17.06-29.64%),
borneol (6.66-17.47%), caryophyllene oxide (8.30-14.01%), tau-cadinol (4.87
9.16%), beta-caryophyllene (3.54-6.57%), 1.8-cineole (1.94-5.87%), beta-pinene
(1.48-3.05%), geranyl acetate (0.56-2.14%) and myrtenal (0.65-2.14%).
PMID- 28421829
TI - Hydrocephalus and trigeminal neuralgia: exploring the association and management
options.
AB - We report the successful surgical management of three patients with trigeminal
neuralgia and hydrocephalus. MRI revealed no neurovascular contact at the
trigeminal root entry zone. Trigeminal neuralgic symptoms were controlled
following alleviation of hydrocephalus. We hypothesize that trigeminal nerve
traction, secondary to hydrocephalus, as the cause for their trigeminal
neuralgia.
PMID- 28421831
TI - A Novel Automated Slide-Based Technology for Visualization, Counting, and
Characterization of the Formed Elements of Blood: A Proof of Concept Study.
AB - CONTEXT: - A novel automated slide-based approach to the complete blood count and
white blood cell differential count is introduced. OBJECTIVE: - To present proof
of concept for an image-based approach to complete blood count, based on a new
slide preparation technique. A preliminary data comparison with the current flow
based technology is shown. DESIGN: - A prototype instrument uses a proprietary
method and technology to deposit a precise volume of undiluted peripheral whole
blood in a monolayer onto a glass microscope slide so that every cell can be
distinguished, counted, and imaged. The slide is stained, and then multispectral
image analysis is used to measure the complete blood count parameters. Images
from a 600-cell white blood cell differential count, as well as 5000 red blood
cells and a variable number of platelets, that are present in 600 high-power
fields are made available for a technologist to view on a computer screen. An
initial comparison of the basic complete blood count parameters was performed,
comparing 1857 specimens on both the new instrument and a flow-based hematology
analyzer. RESULTS: - Excellent correlations were obtained between the prototype
instrument and a flow-based system. The primary parameters of white blood cell,
red blood cell, and platelet counts resulted in correlation coefficients (r) of
0.99, 0.99, and 0.98, respectively. Other indices included hemoglobin (r = 0.99),
hematocrit (r = 0.99), mean cellular volume (r = 0.90), mean corpuscular
hemoglobin (r = 0.97), and mean platelet volume (r = 0.87). For the automated
white blood cell differential counts, r values were calculated for neutrophils (r
= 0.98), lymphocytes (r = 0.97), monocytes (r = 0.76), eosinophils (r = 0.96),
and basophils (r = 0.63). CONCLUSIONS: - Quantitative results for components of
the complete blood count and automated white blood cell differential count can be
developed by image analysis of a monolayer preparation of a known volume of
peripheral blood.
PMID- 28421830
TI - Sinonasal Inverted Papilloma: Risk Factors for Local Recurrence After Surgical
Resection.
AB - OBJECTIVES: Sinonasal inverted papillomas (SIP) present a potential for
recurrence years after the surgery, but most studies report short-term follow-up,
and risk factors for recurrence are still debated. Furthermore, several
classifications are described, and no consensus exists regarding which one should
be used. The aims of this study were to report our long-term results, investigate
for potential risk factors for recurrence, and compare the existing 8 staging
systems. METHODS: Over a 28-year period, 110 patients with a diagnosis of SIP
were enrolled. The median follow-up time was 55.6 months. RESULTS: In
multivariate Cox regression modeling, history of previous surgery was the only
variable associated with recurrence (hazard ratio = 4.91, 95% CI, 1.80-13.39).
Recurrences occurred up to 60 months after the surgery. Among the 8 staging
systems, none proved to be associated with recurrence. CONCLUSION: The only
factor associated with recurrence of SIP was prior surgery, probably
corresponding to an incomplete initial resection. Due to late recurrences, an
extended follow-up of at least 5 years is mandatory. In the absence of a
classification predicting prognosis, Krouse's staging system should be used to
homogenize studies' report since it is the most widely used.
PMID- 28421832
TI - Experimental induction of chicken amyloid A amyloidosis in white layer chickens
by inoculation with inactivated vaccines.
AB - We investigated the amyloidogenic potential of inactivated vaccines and the
localized production of serum amyloid A (SAA) at the injection site in white
layer chickens. Hens in the treated group were injected intramuscularly three
times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine
and multivalent viral and bacterial inactivated oil-emulsion vaccines at two-week
intervals. Chickens in the control group did not receive any inoculum. In the
treated group, emaciation and granulomas were present, while several chickens
died between 4 and 6 weeks after the first injection. Hepatomegaly was seen at
necropsy, and the liver parenchyma showed inconsistent discolouration with patchy
green to yellowish-brown areas, or sometimes red-brown areas with haemorrhage.
Amyloid deposition in the liver, spleen, duodenum, and at injection sites was
demonstrated using haematoxylin and eosin staining, Congo red, and
immunohistochemistry. The incidence of chicken amyloid A (AA) amyloidosis was 47%
(28 of 60) in the treated group. In addition, RT-PCR was used to identify chicken
SAA mRNA expression in the liver and at the injection sites. Furthermore, SAA
mRNA was detected by in situ hybridization in fibroblasts at the injection sites,
and also in hepatocytes. We believe that this is the first report of the
experimental induction of systemic AA amyloidosis in white layer chickens
following repeated inoculation with inactivated vaccines without the
administration of amyloid fibrils or other amyloid-enhancing factors.
PMID- 28421833
TI - A Multidimensional Study of Vocal Function Following Radiation Therapy for
Laryngeal Cancers.
AB - BACKGROUND: Radiation therapy (XRT) has proven to be an effective curative
modality in the treatment of laryngeal cancers. However, XRT also has deleterious
effects on vocal function. AIM: To demonstrate the multidimensional nature of
deficits in vocal function as a result of radiation therapy for laryngeal cancer.
STUDY DESIGN: Cohort study. METHODOLOGY: Vocal function parameters were chosen
from the 5 domains of voice assessment to complete a multidimensional assessment
battery. Adults irradiated (XRT group) for laryngeal cancers were compared to a
control group of individuals with no history of head and neck cancers or
radiation therapy. The control group was matched in age, sex, and pack years of
smoking. RESULTS: Eighteen participants were recruited for the study. The XRT
group demonstrated significantly worse clinical values as compared to the control
group across select parameters in the each of the 5 domains of voice assessment.
DISCUSSION: Radiation therapy for laryngeal cancers results in multidimensional
deficits in vocal function. Notably, these deficits persist long term. In the
present study sample, multidimensional deficits were persistent 2 to 7 years
following completion of XRT. The observed multidimensional persistent vocal
difficulties highlight the importance of vocal rehabilitation in the irradiated
larynx cancer population.
PMID- 28421835
TI - Symptomatic tension pneumocephalus following Palacos(r) cranioplasty in a shunted
patient.
AB - Tension pneumocephalus is an exceedingly rare complication of cerebrospinal fluid
diversion occurring after surgery, trauma or spontaneous fistula formation. We
report a case in a patient with a ventriculoperitoneal shunt who developed
symptomatic tension pneumocephalus via a skin defect within 24 hours of
undergoing bone cement cranioplasty.
PMID- 28421834
TI - Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk
of Cardiovascular Disease in Men with Hypogonadism: A Real-Life Observational
Registry Study Setting Comparing Treated and Untreated (Control) Groups.
AB - OBJECTIVES: In the absence of large, prospective, placebo-controlled studies of
longer duration, substantial evidence regarding the safety and risk of
testosterone (T) therapy (TTh) with regard to cardiovascular (CV) outcomes can
only be gleaned from observational studies. To date, there are limited studies
comparing the effects of long-term TTh in men with hypogonadism who were treated
or remained untreated with T, for obvious reasons. We have established a registry
to assess the long-term effectiveness and safety of T in men in a urological
setting. Here, we sought to compare the effects of T on a host of parameters
considered to contribute to CV risk in treated and untreated men with
hypogonadism (control group). PATIENTS AND METHODS: Observational, prospective,
cumulative registry study in 656 men (age: 60.7 +/- 7.2 years) with total T
levels <=12.1 nmol/L and symptoms of hypogonadism. In the treatment group, men (n
= 360) received parenteral T undecanoate (TU) 1000 mg/12 weeks following an
initial 6-week interval for up to 10 years. Men (n = 296) who had opted against
TTh served as controls. Median follow-up in both groups was 7 years. Measurements
were taken at least twice a year, and 8-year data were analyzed. Mean changes
over time between the 2 groups were compared by means of a mixed-effects model
for repeated measures, with a random effect for intercept and fixed effects for
time, group, and their interaction. To account for baseline differences between
the 2 groups, changes were adjusted for age, weight, waist circumference, fasting
glucose, blood pressure, and lipids. RESULTS: There were 2 deaths in the T
treated group, none was related to CV events. There were 21 deaths in the
untreated (control) group, 19 of which were related to CV events. The incidence
of death in 10 patient-years was 0.1145 in the control group (95% confidence
interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95%
CI: 0.0023-0.0368; P < .000); the estimated difference between groups was 0.0804
(95% CI: 0.0189-0.3431; P < .001). The estimated reduction in mortality for the T
group was between 66% and 92%. There were also 30 nonfatal strokes and 26
nonfatal myocardial infarctions in the control group and none in the T-treated
group. CONCLUSION: Long-term TU was well tolerated with excellent adherence
suggesting a high level of patient satisfaction. Mortality related to CV disease
was significantly reduced in the T-group.
PMID- 28421836
TI - Analytical confirmation of synthetic cannabinoids in a cohort of 179
presentations with acute recreational drug toxicity to an Emergency Department in
London, UK in the first half of 2015.
AB - CONTEXT: Synthetic cannabinoid receptor agonists are the largest group of new
psychoactive substances reported in the last decade; in this study we
investigated how commonly these drugs are found in patients presenting to the
Emergency Department with acute recreational drug toxicity. METHODS: We conducted
an observational cohort study enrolling consecutive adult patients presenting to
an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with
acute recreational drug toxicity. Residual serum obtained from a serum sample
taken as part of routine clinical care was analyzed using high-resolution
accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum
clinical data were obtained from ED medical records. RESULTS: 18 (10%) of the 179
patient samples were positive for synthetic cannabinoid receptor agonists. The
most common was 5F AKB-48 (13 samples, concentration 50-7600 pg/ml), followed by
5F PB-22 (7, 30-400 pg/mL), MDMB-CHMICA (7, 80-8000 pg/mL), AB-CHMINACA (3, 50
1800 pg/mL), Cumyl 5F-PINACA (1, 800 pg/mL) and BB-22 (1, 60 pg/mL). Only 9/18
(50%) in whom synthetic cannabinoid receptor agonists were detected self-reported
synthetic cannabinoid receptor agonist use. The most common clinical features
were seizures and agitation, both recorded in four (22%) individuals. Fourteen
patients (78%) were discharged from the ED, one of the four admitted to hospital
was admitted to critical care. CONCLUSIONS: Synthetic cannabinoid receptor
agonists were found in 10% of this cohort with acute recreational drug toxicity
but self-reported in only half of these. This suggests that presentations to the
ED with acute synthetic cannabinoid receptor agonist toxicity may be more common
than reported.
PMID- 28421837
TI - Pediatric ingestion of vilazodone compared to other selective serotonin reuptake
inhibitor medications.
AB - BACKGROUND: Unintentional ingestion of selective serotonin reuptake inhibitor
(SSRI) medications is common amongst children <6 years of age. Current evidence
based management guidelines are based on a low incidence of significant medical
outcomes in these children. OBJECTIVE: To describe and compare outcomes of
pediatric exposures to vilazodone with other SSRIs. METHODS: A retrospective
observational case series analysis of both single and polysubstance SSRI
exposures amongst children <6 years old reported to the National Poison Data
System (NPDS). RESULTS: 11,384 SSRI exposures in children <6 years of age
reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone
only accounted for 5.9% of all exposures, but resulted in the highest proportion
of health care facility admission compared to other SSRIs, both in single
substance (165 of 531 (31.1%); OR 9.0 [7.3-11.2]) and polysubstance (57 of 107
(53.3%); OR 4.1 [2.7-6.2]) exposures. Children exposed to vilazodone also have
higher odds of experiencing a major or moderate outcome in single (134 of 531
(25.2%); OR 20.5 [15.5-27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7
9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such
as seizure and coma, were more common among the vilazodone exposures.
CONCLUSIONS: Exposure to vilazodone in this age group results in an increased
rate of hospitalization as well as more severe clinical effects as compared to
other SSRIs. Current evidence-based SSRI exposure management guidelines may not
be appropriate for the management of vilazodone ingestion in this age group.
PMID- 28421838
TI - Self-reported cocaine use is not associated with elevations in high-sensitivity
troponin I.
AB - OBJECTIVE: High-sensitivity troponin (hsTn) assays detect 10 times lower
concentrations of cardiac troponin than conventional assays. We examined the
effects of self-reported cocaine use to determine whether those with acute
cocaine use being evaluated for ACS are more likely to have elevated hsTnI than
those nonusers being evaluated for ACS. METHODS: We conducted a sub-analysis of a
prospective cohort of ED patients evaluated for acute coronary syndrome. Recent
cocaine use was determined by structured patient interviews. High-sensitivity
troponin (Abbott) and conventional troponin I (Abbott, cTnI) were measured on
samples drawn at presentation. Urine toxicology screen for cocaine metabolite was
obtained at the discretion of treating clinicians. RESULTS: Of 1862 patients
enrolled, 444 reported prior cocaine use and 99 reported cocaine use within the
preceding month. Median hsTn in patients with last cocaine use within 24 h, 2-7
days, 1 week-1 month, >1 month, and no prior cocaine use were: 9 (IQR: 3-17)
ng/L, 6 (IQR: 3-24.3) ng/L, 6 (IQR: 3-89.5) ng/L, 3 (IQR: 3-18.5) ng/L and 3
(IQR: 3-17) ng/L, respectively. Urine toxicology assays (UTox) for cocaine were
performed in 640 (34.4%) patients. The median hsTn for those who were UTox+, UTox
- and those without a UTox were: 9 ng/L (IQR: 3-48.5), 9 ng/L (IQR: 3-40) and 3
ng/L (IQR: 3-12), respectively. There were no differences in the prevalence of
new troponin elevations (hsTn >99th percentile but cTnI <99th percentile) in
those with recent cocaine use compared to those without recent cocaine use.
CONCLUSIONS: In this first investigation of hsTn in patients with self-reported
recent cocaine use, we have determined that hsTn does not lead to an increase in
the prevalence of troponin elevation in cocaine users.
PMID- 28421839
TI - Extracorporeal cardiopulmonary resuscitation after brown recluse envenomation.
PMID- 28421840
TI - Limitations of the evidence supporting use of undetectable acetaminophen levels
obtained <4 hours post-ingestion to rule out toxicity.
PMID- 28421841
TI - Adolescent with prolonged toxidrome.
AB - A 13-year-old female was presented to the emergency department following an
intentional ingestion. The patient developed significant toxicity including
multiple, discreet tonic-clonic seizures. Despite appropriate resuscitation and
antidotal management, the patient's symptoms persisted for more than 36 hours
post-ingestion. An upright abdominal radiograph was performed revealing a
radiopacity suggesting a pharmacobezoar. An esophagogastroduodenoscopy was
performed with successful removal of a tennis ball-sized pharmacobezoar. The
patient's symptoms subsequently subsided and she recovered fully with no
neurologic deficits. Diphenhydramine has not been previously identified as a
medication likely to form a pharmacobezoar and has not been shown to be
radiopaque. Though bezoar formation is a rare clinical scenario, it is one that
toxicologists must consider in patients with clinical courses that persist far
beyond expected based on known toxicokinetic principles.
PMID- 28421842
TI - The management of ventricular dysrhythmia in aconite poisoning.
AB - INTRODUCTION: Aconite poisoning is relatively rare but is frequently complicated
by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite
alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to
the presence of an admixture of alkaloids present in all parts of the plant. The
major target of these aconite alkaloids is the fast voltage-gates sodium channel,
where they cause persistent activation. This blockade of the channel in the
activated state promotes automaticity within the ventricular myocardium and the
generation of ventricular arrhythmias. Aconitine-induced arrhythmias: Aconite
alkaloids are known to cause many different types of disturbance of heart rhythm.
However, this focused review specifically looks at ventricular rhythm
disturbances, namely ventricular ectopy, ventricular tachycardia, torsades des
pointes and ventricular fibrillation. OBJECTIVE: The objective of this review was
to identify the outcome of anti-dysrhythmic strategies from animal studies and
case reports in humans in order to guide the management of ventricular
dysrhythmias in aconite poisoning in humans. METHODS: A review of the literature
in English was conducted in PubMed and Google Scholar from 1966 to July 2016
using the search terms "aconite/aconitine"; "aconite/aconitine + poisoning" and
"aconite/aconitine + dysrhythmia". 168 human case-reports and case-series were
identified by these searches, of which 103 were rejected if exposure to aconite
did not result in ventricular dysrhythmias, if it was uncertain as to whether
aconite had been ingested, if other agents were co-ingested, if there was
insufficient information to determine the type of treatments administered or if
there was insufficient information to determine outcome. Thus, 65 case reports of
probable aconite poisoning that resulted in ventricular dysrhythmias were
identified. Toxicokinetic data in aconite poisoning: Data were only available in
three papers; the presence of ventricular rhythm disturbances directly correlated
with the concentration of aconite alkaloids in the plasma. MANAGEMENT: 54 of 65
cases developed ventricular tachycardia, six developed torsades des pointes, 15
patients developed ventricular fibrillation, 10 developed ventricular ectopics
and one developed a broad complex tachycardia not otherwise specified; each
dysrhythmia was regarded as separate and patients may have had more than one
dysrhythmia. 10 patients died, giving a mortality of 15%. In total, 147
treatments were administered to 65 patients. 46 of the interventions were
assessed by the authors as having been associated with successful restoration of
sinus rhythm. Flecainide administration was accompanied by dysrhythmia
termination in six of seven cases. Mexiletine was connected with correcting
dysrhythmias in 3 of 3 cases. Procainamide administration was associated with
return to sinus rhythm in 2 of 2 cases. Prolonged cardio-pulmonary resuscitation
was administered to 15 patients where it was associated with a return to sinus
rhythm in nine of these. Amiodarone was linked to success in correcting
dysrhythmias in 11 of 20 cases. Cardiopulmonary bypass use was associated with a
return to sinus rhythm in four out of six cases. Epinephrine was documented as
being employed on four occasions, and was associated with a restoration of sinus
rhythm on two of these. Magnesium sulphate administration was accompanied by
dysrhythmia termination in two of nine cases. Direct cardioversion was associated
with a return of sinus rhythm in 5 of 30 cases. However, it is not certain
whether the drug treatment influenced the course of the dysrhythmia. CONCLUSIONS:
Based on the evidence available from human case reports, flecainaide or
amiodarone appear to be more associated with a return to sinus rhythm than
lidocaine and/or cardioversion, although it is not established whether the
administration of treatment caused reversion to normal sinus rhythm. The
potential beneficial effects of amiodarone were not observed in animal studies.
This may be due to intra-species differences between ion channels or relate to
the wider cardiovascular toxicity of aconite that extends beyond arrhythmias.
Prolonged cardiopulmonary resuscitation and cardiopulmonary bypass should be
considered as an integral part of good clinical care as "time-buying" strategies
to allow the body to excrete the toxic alkaloids. There may also be a role for
mexiletine, procainamide and magnesium sulphate.
PMID- 28421843
TI - Reply to: Limitations of the evidence supporting use of undetectable
acetaminophen levels obtained <4 hours post-ingestion to rule out toxicity.
PMID- 28421844
TI - Accuracy of the paracetamol-aminotransferase multiplication product to predict
hepatotoxicity in modified-release paracetamol overdose.
AB - CONTEXT: The paracetamol-aminotransferase multiplication product (APAP * ALT) is
a risk predictor of hepatotoxicity that is somewhat independent of time and type
of ingestion. However, its accuracy following ingestion of modified-release
formulations is not known, as the product has been derived and validated after
immediate-release paracetamol overdoses. OBJECTIVE: The aim of this retrospective
cohort study was to evaluate the accuracy of the multiplication product to
predict hepatotoxicity in a cohort of patients with modified-release paracetamol
overdose. METHODS: We assessed all patients with modified-release paracetamol
overdose presenting to our hospital network from October 2009 to July 2016.
Ingestion of a modified-release formulation was identified by patient self-report
or retrieval of the original container. Hepatotoxicity was defined as peak
alanine aminotransferase >=1000 IU/L, and acute liver injury (ALI) as a doubling
of baseline ALT to more than 50 IU/L. RESULTS: Of 1989 paracetamol overdose
presentations, we identified 73 modified-release paracetamol exposures treated
with acetylcysteine. Five patients developed hepatotoxicity, including one who
received acetylcysteine within eight hours of an acute ingestion. No patient with
an initial multiplication product <10,000 mg/L * IU/L developed hepatotoxicity
(sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity
fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L * IU/L. When
calculated within eight hours of ingestion, mild elevations of the multiplication
product fell quickly on repeat testing in patients without ALI or hepatotoxicity.
CONCLUSIONS: In modified-release paracetamol overdose treated with
acetylcysteine, the paracetamol-aminotransferase multiplication product
demonstrated similar accuracy and temporal profile to previous reports involving
mostly immediate-release formulations. Above a cut-point of 10,000 mg/L * IU/L,
it was very strongly associated with the development of acute liver injury and
hepatotoxicity, especially when calculated more than eight hours post-ingestion.
When below 1500 mg/L * IU/L the likelihood of developing hepatotoxicity was very
low. Persistently high serial multiplication product calculations were associated
with the greatest risk of hepatotoxicity.
PMID- 28421845
TI - An alarming increase in local pentobarbital-related suicides.
PMID- 28421846
TI - Clinical toxicology: past and future.
PMID- 28421847
TI - Authors' Response to Letter to the Editor, Part II.
PMID- 28421848
TI - An Evaluation of a Community-Oriented Policing Program in Taiwan.
AB - This study was conducted to evaluate the effect of a community-oriented policing
(COP) by documenting results for 16 quantitative outcome variables, including
crime incidents, crime clearance, residents' subjective feelings regarding police
performance and community safety, and job satisfaction among police officers. The
statistical techniques used to analyze the data involved ARIMA interrupted time
series, t tests, the Wilcoxon paired signed-rank test, and Pearson's correlation.
The quantitative results observed indicated that the program had a positive
effect on resident's perceptions for some police performance outcomes and for job
satisfaction among police officers. However, there was only a minimal program
effect on crime occurrence, crime clearance, and residents' perceptions of crime.
Using a combination of review of prior research and qualitative interview data
collected from 10 local stakeholders, we provided insightful informed actor-based
and temporal contextual explanations for the unexpected quantitative findings.
PMID- 28421849
TI - Infliximab crystal structures reveal insights into self-association.
AB - Aggregation and self-association in protein-based biotherapeutics are critical
quality attributes that are tightly controlled by the manufacturing process.
Aggregates have the potential to elicit immune reactions, including neutralizing
anti-drug antibodies, which can diminish the drug's efficacy upon subsequent
dosing. The structural basis of reversible self-association, a form of non
covalent aggregation in the native state, is only beginning to emerge for many
biologics and is often unique to a given molecule. In the present study, crystal
structures of the infliximab (Remicade) Fc and Fab domains were determined. The
Fab domain structures are the first to be reported in the absence of the antigen
(i.e., tumor necrosis factor), and are consistent with a mostly rigid
complementarity-determining region loop structure and rotational flexibility
between variable and constant regions. A potential self-association interface is
conserved in two distinct crystal forms of the Fab domain, and solution studies
further demonstrate that reversible self-association of infliximab is mediated by
the Fab domain. The crystal structures and corresponding solution studies help
rationalize the propensity for infliximab to self-associate and provide insights
for the design of improved control strategies in biotherapeutics development.
PMID- 28421850
TI - Semen parameters and pregnancy rates after microsurgical varicocelectomy in
primary versus secondary infertile men.
AB - In a prospective study, the outcomes of microsurgical varicocelectomy in men with
primary versus secondary infertility were compared. Ninety-two infertile men with
a varicocele were included. They were classified into those with primary
infertility (n = 57) and secondary infertility (n = 35). Clinical data, semen
parameters and scrotal ultrasound finding were available for all patients and
microsurgical varicocelectomy was performed on all of them. Spontaneous pregnancy
rates and improvement in semen parameters in those men with primary versus
secondary infertility were recorded 1 year after surgery. Preoperatively, there
was no significant difference in the mean semen parameters in both groups (p >
0.05) and the mean semen parameters showed no significant difference between men
with primary and secondary infertility. After microsurgical varicocelectomy, the
mean semen parameters improved significantly in both group (p < 0.05 for each),
but there were no significant difference in mean semen parameters between men
with primary versus secondary infertility (p > 0.05 for each). After adjustment
for patient and partner ages, the pregnancy rate at the end of the follow-up
period did not significantly differ between the primary (24/57, 42.1%) and
secondary (11/35, 31.4%) infertility group (Pearson's Chi-squared = 1.05). We
concluded from this study that semen parameters and pregnancy rates after
microsurgical varicocelectomy were similar between men with primary and secondary
infertility.
PMID- 28421851
TI - Global and multi-focal changes in cerebral blood flow during subthalamic nucleus
stimulation in Parkinson's disease.
AB - Electrical stimulation of subthalamic nuclei (STN) is a widely used therapy in
Parkinson's disease (PD). While deep brain stimulation (DBS) of the STN alters
the neurophysiological activity in basal ganglia, the therapeutic mechanism has
not been established. A positron emission tomography (PET) study of cerebral
blood flow (CBF) during speech production in PD subjects treated with STN-DBS
found significant increases in global (whole-brain) CBF.1 That study utilized a
series of whole-slice regions of interest to obtain global CBF values. The
present study examined this effect using a voxel-based principal component
analysis (PCA) combined with Fisher's linear discriminant analysis (FLDA) to
classify STN-DBS on versus STN-DBS off whole-brain images. The approach yielded
wide-spread CBF changes that classified STN-DBS status with accuracy,
sensitivity, and specificity approaching 90%. The PCA component of the analysis
supported the observation of a global CBF change during STN-DBS. The FLDA
component demonstrated wide-spread multi-focal CBF changes. Further, CBF
measurements related to a number of subject characteristics when STN-DBS was off,
but not when it was on, suggesting that the normal relationship between CBF and
behavior may be disrupted by this form of neuromodulation.
PMID- 28421852
TI - The Priorities of Iranian Male Adolescents Health Needs.
AB - Health in the adolescence period guarantees the next generation's health. The
assessment of health needs is the first stage for the implementation of health
promotion interventions. This study aimed to assess the priorities of male
adolescent's health needs in Tehran, Iran, in year 2015. This cross-sectional
correlational study was conducted with 1,200 male adolescents aged between 13 and
18 years. Single male adolescents studying in public guidance and high schools in
Tehran, Iran, in year 2015 were chosen using a random multistage sampling method.
Data were collected using the male adolescent health need assessment scale. The
data were analyzed using descriptive and inferential statistics. It was found
that while the lowest score was for the domain of sexual health, other domains
had average or higher than average scores. More attention should be paid to the
sexual health needs of male adolescents. Policy makers need to design strategies
that help meet the health needs of male adolescents.
PMID- 28421853
TI - Pentraxin 3 and lipid profile status in pregnancy.
AB - Hyperlipidaemia and hypercholesterolaemia are risk factors of atherosclerosis and
cardiovascular disease. The reference range of lipids during pregnancy has not
yet been clearly set. This study sought to measure lipid parameters and pentraxin
(PTX) 3 levels in low-risk pregnant women. The participants had serial blood
samples taken between their 6th-9th week, 10th-13th week, 14th-19th week, 24th
29th week and 35th-40th week (as long as there were no contractions), during the
labour period, and 2 days after delivery. The same tests were carried out on cord
blood after delivery. There were 116 participants, of which 72 were included in
the study and 44 were excluded. Total-c, HDL-c, LDL-c, TG and PTX3 increased as
the pregnancy progressed. During labour, Total-c, HDL-c, LDL-c and PTX3
increased, but TG decreased. After delivery, TG and PTX3 increased but other
parameters decreased from the value measured during the 35th-40th week. This
study measured changes in lipid profiles and PTX3 during pregnancy, labour and
after delivery, establishing a foundation for future studies.
PMID- 28421854
TI - Reduction of BOLD interference in pseudo-continuous arterial spin labeling:
towards quantitative fMRI.
AB - Fluctuations in blood-oxygenation level dependent (BOLD) signal and perfusion
affect the quantification of changes in cerebral blood flow (CBF), coupled to
neuronal activity, in arterial spin labeling (ASL). Subtraction methods for
control and labeled MR images (i.e. pair-wise, surround subtraction, and
subtraction of sinc-interpolated images), postulated to mitigate this
interference in pseudo-continuous ASL (pCASL), were evaluated by comparison with
quantitative 15O-water PET. At rest, a good agreement in the CBF values was found
between PET and MRI for each of the subtraction methods. Stimulation of the
visual system resulted in a regional CBF increase in the occipital lobe, which
was detectable in both modalities. Bland-Altman analysis showed a systematic
underestimation of the CBF values during activation in MRI. Evaluation of the
relative CBF change induced by neuronal stimulation showed good inter-modality
agreement for the three subtraction methods. Perfusion data obtained with each
subtraction method followed the stimulation paradigm without significant
differences in the correlation patterns or in the time lag between stimulation
and perfusion response. Comparison to the gold standard confirmed the
detectability of a neuronal stimulation pattern by pCASL. The results indicate
that the combined use of background suppression and short TE reduces the BOLD
weighting in the pCASL signal.
PMID- 28421855
TI - Midterm Outcomes After Infrapopliteal Interventions in Patients With Critical
Limb Ischemia Based on the TASC II Classification of Below-the-Knee Arteries.
AB - PURPOSE: To analyze the relationship between the new TransAtlantic Inter-Society
Consensus (TASC II) infrapopliteal classification and limb outcomes among
patients with critical limb ischemia (CLI). METHODS: A single-center
retrospective study was performed on 166 consecutive CLI patients (mean age 71
years; 113 men) undergoing endovascular treatment of 244 infrapopliteal lesions
from 2006 to 2013. Patient, procedural, angiographic, and limb outcomes were
compared for the new TASC A/B vs C/D classification for infrapopliteal lesions.
Binary restenosis was determined by a peak systolic velocity ratio >2.0 by duplex
ultrasound on follow-up at 1, 3, 6, and 12 months. RESULTS: Seventy-two (43.4%)
patients had TASC A/B lesions, while 94 (56.6%) had TASC C/D patterns of
infrapopliteal disease. Baseline demographics and tissue loss (93% vs 94%,
p=0.59) were similar between the groups. TASC A/B lesions were shorter (53+/-35
vs 170+/-83 mm, p<0.001), less severely stenosed (77%+/-24% vs 93%+/-14%,
p<0.001), had a larger target vessel diameter (2.9+/-0.5 vs 2.6+/-0.5 mm,
p<0.001), and were less frequently chronic total occlusions (24% vs 64%, p<0.001)
compared with the TASC C/D group. Three-year freedom from both amputation (85% vs
67%, p=0.02) and major adverse limb events (79% vs 61%, p=0.02) were
significantly higher in the TASC A/B group. Technical success rates (95% vs 80%,
p<0.001) and 1-year primary patency (58% vs 51%, p=0.04) were higher in the A/B
group. Overall 3-year survival was similar between the groups (96% A/B vs 88%
C/D, p=0.2). CONCLUSION: TASC C/D infrapopliteal lesions are associated with
higher amputation and major adverse limb events rates and lower primary patency
compared with TASC A/B infrapopliteal lesions. Further studies are needed to
assess the association between TASC C/D infrapopliteal lesions and clinical
outcomes in patients with CLI.
PMID- 28421856
TI - Evaluation of the simplified acute physiology score (SAPS-OB) in critically ill
obstetric patients.
PMID- 28421857
TI - Risk of solid cancer in low dose-rate radiation epidemiological studies and the
dose-rate effectiveness factor.
AB - PURPOSE: Estimated radiation risks used for radiation protection purposes have
been based primarily on the Life Span Study (LSS) of atomic bomb survivors who
received brief exposures at high dose rates, many with high doses. Information is
needed regarding radiation risks from low dose-rate (LDR) exposures to low linear
energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR
epidemiologic studies that provide dose-response estimates of total solid cancer
risk in adulthood in comparison to corresponding LSS risks, in order to estimate
a dose rate effectiveness factor (DREF). MATERIALS AND METHODS: We identified 22
LDR studies with dose-response risk estimates for solid cancer after minimizing
information overlap. For each study, a parallel risk estimate was derived from
the LSS risk model using matching values for sex, mean ages at first exposure and
attained age, targeted cancer types, and accounting for type of dosimetric
assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR
Gy-1) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta
analysis of the risk ratios was conducted. The reciprocal of the resultant risk
ratio provided an estimate of the DREF. RESULTS: The meta-analysis showed a
LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19
studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts
with only incidence data also were added, implying a DREF with values around 3,
but statistically compatible with 2. However, the analyses were highly dominated
by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk
ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09,
0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta
analyses that included only cohorts in which the mean dose was <100 mGy yielded a
risk ratio of 1.06 (95% CI 0.30, 1.83) for solid cancer mortality and 0.58 (95%
CI 0.10, 1.06) for mortality + incidence data. CONCLUSIONS: The interpretation of
a best estimate for a value of the DREF depends on the appropriateness of
including the Mayak study. This study indicates a range of uncertainty in the
value of DREF between 1 and about 2 after protracted radiation exposure. The LDR
data provide direct evidence regarding risk from exposures at low dose rates as
an important complement to the LSS risk estimates used for radiation protection
purposes.
PMID- 28421858
TI - Multi-step treatment for acquired alexia and agraphia (Part I): efficacy,
generalisation, and identification of beneficial treatment steps.
AB - Reading and writing impairments are common in individuals with post-stroke
aphasia. Treatment typically aims to improve the function of one of these
modalities by strengthening aspects of either lexical or sublexical processing.
In the present study, eight adults with acquired alexia and agraphia were
administered a comprehensive treatment targeting specific lexical and sublexical
processes underlying reading and/or writing. Two participants were trained in
reading and six were trained in writing. Throughout treatment, reading and
writing accuracy were monitored for trained items, as well as untrained but
orthographically and semantically related items. Linear mixed effects models
indicated that the most substantial gains were made on trained items in the
trained modality; generalisation to trained items in the untrained modality and
untrained but related items in both modalities was also observed. Participants
improved significantly on a subset of treatment steps intended to address lexical
access and representations, sublexical conversion mechanisms, and the graphemic
and/or phonological buffer processes in both modalities. These results
demonstrate the efficacy of a novel, comprehensive treatment protocol and suggest
that targeting multiple reading and writing processes in conjunction may
facilitate widespread generalisation.
PMID- 28421860
TI - Abstracts of Presentations at the 2017 Southern Division Meeting.
PMID- 28421859
TI - Water Sensation During Passive Propulsion for Expert and Nonexpert Swimmers.
AB - This study determined whether expert swimmers, compared with nonexperts, have
superior movement perception and physical sensations of propulsion in water.
Expert (national level competitors, n = 10) and nonexpert (able to swim 50 m in >
3 styles, n = 10) swimmers estimated distance traveled in water with their eyes
closed. Both groups indicated their subjective physical sensations in the water.
For each of two trials, two-dimensional coordinates were obtained from video
recordings using the two-dimensional direct linear transformation method for
calculating changes in speed. The mean absolute error of the difference between
the actual and estimated distance traveled in the water was significantly lower
for expert swimmers (0.90 +/- 0.71 meters) compared with nonexpert swimmers (3.85
+/- 0.84 m). Expert swimmers described the sensation of propulsion in water in
cutaneous terms as the "sense of flow" and sensation of "skin resistance."
Therefore, expert swimmers appear to have a superior sense of distance during
their movement in the water compared with that of nonexpert swimmers. In
addition, expert swimmers may have a better perception of movement in water. We
propose that expert swimmers integrate sensations and proprioceptive senses,
enabling them to better perceive and estimate distance moved through water.
PMID- 28421862
TI - Lateral Wall Regeneration and Membrane Repair After Attempted Sinus Augmentation
Using a Non-Resorbable Membrane.
PMID- 28421861
TI - The Plant-Dependent Life Cycle of Thecaphora thlaspeos: A Smut Fungus Adapted to
Brassicaceae.
AB - Smut fungi are globally distributed plant pathogens that infect agriculturally
important crop plants such as maize or potato. To date, molecular studies on
plant responses to smut fungi are challenging due to the genetic complexity of
their host plants. Therefore, we set out to investigate the known smut fungus of
Brassicaceae hosts, Thecaphora thlaspeos. T. thlaspeos infects different
Brassicaceae plant species throughout Europe, including the perennial model plant
Arabis alpina. In contrast to characterized smut fungi, mature and dry T.
thlaspeos teliospores germinated only in the presence of a plant signal. An
infectious filament emerges from the teliospore, which can proliferate as haploid
filamentous cultures. Haploid filaments from opposite mating types mate, similar
to sporidia of the model smut fungus Ustilago maydis. Consistently, the a and b
mating locus genes are conserved. Infectious filaments can penetrate roots and
aerial tissues of host plants, causing systemic colonization along the
vasculature. Notably, we could show that T. thlaspeos also infects Arabidopsis
thaliana. Exploiting the genetic resources of A. thaliana and Arabis alpina will
allow us to characterize plant responses to smut infection in a comparative
manner and, thereby, characterize factors for endophytic growth as well as smut
fungi virulence in dicot plants.
PMID- 28421863
TI - A meta-analysis of task-related influences in prospective memory in traumatic
brain injury.
AB - Prospective memory is the ability to remember to do something in the future and
it is essential to every-day functional independence. Traumatic brain injury is
associated with frequent and persistent prospective memory deficits. This study
presents a review and meta-analysis investigating the effects of task parameters
on prospective memory performance of individuals with TBI. Individual studies
using continuous behavioural measures of prospective memory with a sample of
adults with TBI and matched controls were included. Consistent with previous
research, a random effects meta-analysis indicated that TBI groups demonstrated
lower prospective memory performance than control groups (d = 1.10, SE = 0.12,
95% CI = 0.86-1.34). In addition, we found that type of prospective memory cue,
saliency of cues, and complexity of the ongoing task significantly moderated the
difference in prospective memory performance between TBI and control groups.
These findings suggest that prospective memory task parameters should be
considered in the assessment of prospective memory in individuals with cognitive
impairment. In addition, considering the influence of these task parameters would
be useful to develop effective compensatory strategies to reduce prospective
memory failures.
PMID- 28421864
TI - Selfie: Autoimmunity, boon or bane.
AB - The immune system provides protection to tissues damaged by infectious
microrganisms or physical damage. In autoimmune diseases, the immune system
recognizes and attacks its own tissues, i.e., self-destruction. Various agents
such as genetic factors and environmental triggers are thought to play a major
role in the development of autoimmune diseases. A common feature of all
autoimmune diseases is the presence of autoantibodies and inflammation, including
mononuclear phagocytes, autoreactive T lymphocytes, and autoantibody producing B
cells (plasma cells). It has long been known that B cells produce autoantibodies
and, thereby, contribute to the pathogenesis of many autoimmune diseases.
Autoimmune diseases can be classified as organ-specific or non-organ specific
depending on whether the autoimmune response is directed against a particular
tissue or against widespread antigens as in chronic inflammatory autoimmune
diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis
(RA). Both SLE and RA are characterized by the presence of autoantibodies which
play a major role in their etiopathogenesis. SLE is characterized by circulating
antibodies and immune complex deposition that can trigger an inflammatory damage
in organs. RA is a progressive inflammatory disease in which T cells, B cells,
and pro-inflammatory cytokines play a key role in its pathophysiology.
PMID- 28421865
TI - It's not all about moral reasoning: Understanding the content of Moral Case
Deliberation.
AB - BACKGROUND: Moral Case Deliberation is one form of clinical ethics support
described as a facilitator-led collective moral reasoning by healthcare
professionals on a concrete moral question connected to their practice.
Evaluation research is needed, but, as human interaction is difficult to
standardise, there is a need to capture the content beyond moral reasoning. This
allows for a better understanding of Moral Case Deliberation, which may
contribute to further development of valid outcome criteria and stimulate the
normative discussion of what Moral Case Deliberation should contain. OBJECTIVE:
To explore and compare the content beyond moral reasoning in the dialogue in
Moral Case Deliberation at Swedish workplaces. METHODS: A mixed-methods approach
was applied for analysing audio-recordings of 70 periodic Moral Case Deliberation
meetings at 10 Swedish workplaces. Moral Case Deliberation facilitators and
various healthcare professions participated, with registered nurses comprising
the majority. Ethical considerations: No objection to the study was made by an
Ethical Review Board. After oral and written information was provided, consent to
be recorded was assumed by virtue of participation. FINDINGS: Other than 'moral
reasoning' (median (md): 45% of the spoken time), the Moral Case Deliberations
consisted of 'reflections on the psychosocial work environment' to a varying
extent (md: 29%). Additional content comprised 'assumptions about the patient's
psychosocial situation' (md: 6%), 'facts about the patient's situation' (md: 5%),
'concrete problem-solving' (md: 6%) and 'process' (md: 3%). CONCLUSION: The
findings suggest that a restorative function of staff's wellbeing in Moral Case
Deliberation is needed, as this might contribute to good patient care. This
supports outcome criteria of improved emotional support, which may include relief
of moral distress. However, facilitators need a strategy for how to proceed from
the participants' own emotional needs and to develop the use of their emotional
knowing to focus on the ethically difficult patient situation.
PMID- 28421866
TI - Chronic Pain and Psychological Distress Among Older Adults: A National
Longitudinal Study.
AB - This research examines whether unobserved time-stable influences confound the
association between chronic pain and psychological distress in older adults as
well as how race and ethnicity combine with subjective social status (SSS) to
modify the association. In a nationally representative longitudinal survey,
holistically controlling for unobserved time-stable influences using fixed
effects models substantially reduces the pain-depression relationship and
eliminates the overall pain-anxiety relationship. The association with depression
is stronger for Black and Hispanic elders, illustrating a process of double
jeopardy. Black elders with severe pain experience lower anxiety, as do Black
elders with moderate pain and low SSS, which we suggest may be due to the
enervating effects of undermanaged pain. Black elders at high SSS experience
greater anxiety with moderate pain. This research suggests that undermanagement
of chronic pain among racial and ethnic minorities differentiates the association
between pain and distress in late life and especially creates stronger
associations with depression.
PMID- 28421867
TI - Symptom-related attributional biases in schizophrenia and bipolar disorder.
AB - INTRODUCTION: Biases in causal attributions and evidence integration have been
implicated in delusions, but have not been investigated simultaneously to examine
additive or multiplicative effects. It was hypothesised that paranoid delusions
would correlate with self-serving and personalising biases ("defence" model of
paranoia), particularly when these biases were disconfirmed. METHODS: Constrained
principal component analysis was used to investigate differences between
schizophrenia patients (paranoid vs. non-paranoid), bipolar disorder patients,
and healthy controls, as well as to examine the extent to which psychotic
symptoms could predict patterns of responding on a novel attributional bias task
(Attributional Style BADE, or ASB) that requires integrating contextual
information. RESULTS: Although no group differences were found, disorganisation
and manic symptoms correlated with situation attributions and self-blame when
such attributions were unsupported by the available evidence, and depression and
anxiety correlated with other-person and self attributions (not situation
attributions) when confirmed by the available evidence, regardless of diagnosis.
CONCLUSIONS: While group differences accounted for little variance in responses
on the ASB task, a transdiagnostic association between symptoms of psychosis and
the ASB task was observed. This highlights the importance of considering symptom
profiles rather than diagnostic groupings when investigating cognitive biases and
related non-pharmacological treatments.
PMID- 28421868
TI - RKNNMDA: Ranking-based KNN for MiRNA-Disease Association prediction.
AB - Cumulative verified experimental studies have demonstrated that microRNAs
(miRNAs) could be closely related with the development and progression of human
complex diseases. Based on the assumption that functional similar miRNAs may have
a strong correlation with phenotypically similar diseases and vice versa,
researchers developed various effective computational models which combine
heterogeneous biologic data sets including disease similarity network, miRNA
similarity network, and known disease-miRNA association network to identify
potential relationships between miRNAs and diseases in biomedical research.
Considering the limitations in previous computational study, we introduced a
novel computational method of Ranking-based KNN for miRNA-Disease Association
prediction (RKNNMDA) to predict potential related miRNAs for diseases, and our
method obtained an AUC of 0.8221 based on leave-one-out cross validation. In
addition, RKNNMDA was applied to 3 kinds of important human cancers for further
performance evaluation. The results showed that 96%, 80% and 94% of predicted top
50 potential related miRNAs for Colon Neoplasms, Esophageal Neoplasms, and
Prostate Neoplasms have been confirmed by experimental literatures, respectively.
Moreover, RKNNMDA could be used to predict potential miRNAs for diseases without
any known miRNAs, and it is anticipated that RKNNMDA would be of great use for
novel miRNA-disease association identification.
PMID- 28421869
TI - ALK protein expression in pulmonary adenocarcinoma of Tunisian patients.
AB - BACKGROUND: It is now necessary to determine ALK status in order to use targeted
therapy. AIM: herein, we assess immunohistochemical profile of ALK protein in a
series of Tunisian patients with pulmonary adenocarcinoma. MATERIALS AND METHODS:
ALK protein expression was studied applying the D5F3 antibody with a fully
automated Ventana CDx technique on a series of 19 patients. RESULTS: Positive ALK
expression was found in one case (5.2%) corresponding to a papillary
adenocarcinoma which showed a strong granular and homogenous cytoplasmic
staining. The patient was a 30-years-old woman. CONCLUSION: The frequency of
positive ALK expression based on immunohistochemistry in our series was similar
to that reported in the world literature.
PMID- 28421870
TI - Collaborative study on the effect of grinding on the detection of bones from
processed animal proteins in feed by light microscopy.
AB - Bone fragments are essential structures for the detection of processed animal
proteins (PAPs) in feed by light microscopy for official controls according to
Annex VI of European Union Regulation EC/152/2009. The preparation of samples
submitted for analysis requires a grinding step to make them suitable for
microscopic slide preparation and observation. However, there are no technical
guidelines set down for this step despite the fact that it can lead to an
increase in bone numbers due to fragmentation. This was demonstrated by an in
house study carried out by the Irish National Reference Laboratory (NRL) for
animal protein detection. The present collaborative study investigated the
possible effects of three different grinding conditions on the final result for a
feed adulterated with 0.05 and 0.01% (w/w) of PAP. The microscopic analysis
either combined or not with an Alizarin Red staining was carried out by 10
different laboratories. The results demonstrated that although a large variation
in the numbers of bone fragments was noted, five of the six different
grinding/staining combinations applied at two levels of PAP adulteration did not
significantly (at p = 0.05) differ from one another. The only exception occurred
when grinding the feed containing 0.05% of PAP with a rotor mill equipped with a
0.5-mm sieve and combined with a staining which resulted in a greater number of
bone fragments by forced fragmentation. Overall, the impact of the
grinding/staining combinations on the final results was shown to be negligible
when considering the regulatory limit of detection (LOD) requirement for the
method and the current rules of implementation of the light microscopic method.
From a total of 180 analyses carried out on the feed matrix containing 0.05% of
PAP no false-negative result was observed, and at a level of 0.01% PAP only 10
false-negative results occurred.
PMID- 28421871
TI - Exploring predictors of work competence in schizophrenia: The role of theory of
mind.
AB - In schizophrenia employment rate is dramatically low, also among patients
receiving job support interventions. Recent studies showed a direct relationship
between neurocognitive deficits and work functioning, as well as proving the
benefits of combined neurocognitive and work interventions. Current evidence also
supports a role of Theory of Mind (ToM), on work functioning. However, the effect
of integrated rehabilitation programmes including a social cognitive training on
job outcome is still less explored. The aim of this pilot study is to investigate
the relationship between work competence and clinical factors, neurocognitive and
ToM abilities, as well as to explore the effect of neurocognitive and ToM
treatments combined with work therapy. Thirty-seven outpatients with
schizophrenia were assigned to either a Computer-assisted Cognitive Remediation
(CACR) plus work therapy group (WTG) or to CACR and WTG added to ToM
Intervention, both followed by a job support programme. All patients were
assessed for psychopathology, neurocognition, ToM and work functioning. Work
outcome was significantly predicted by age at onset, neurocognitive abilities and
the degree of ToM improvement after the specific intervention. This study
provides preliminary insight on predictors of work competence in schizophrenia,
highlighting the importance of ToM abilities.
PMID- 28421872
TI - Role of valued living and associations with functional outcome following
traumatic brain injury.
AB - Valued living (VL) is associated with improved enjoyment and engagement with
daily activities despite negative emotional state or ongoing pain. However, the
role of VL in recovery following traumatic brain injury (TBI) has yet to be
investigated. This study aimed to examine changes in VL over the course of
recovery and variables associated with VL. Participants with moderate-to-severe
TBI were recruited from a rehabilitation hospital in three cohorts: "Early" (n =
25), "Mid" (n = 9) and "Late" (n = 36) post-TBI. All participants were assessed
at time of recruitment and 12 months later. The main measure was the Valued
Living Questionnaire. Compared to pre-injury estimates, VL was significantly
reduced at 12 months post-injury. Levels of VL remained reduced between 2 and 3
years and increased between 3 and 6 years post-injury. VL was strongly associated
with improved functional and psychosocial outcomes. Changes in VL occur over at
least 3-5 years post-injury, with 12 months post-TBI a suitable time for
intervention given VL remains low over the next 24 to 36 months post injury.
Targeted intervention to modify values and/or valued activities to be consistent
with post-injury capacity could improve rates of return to pre-injury levels of
VL.
PMID- 28421873
TI - Facial Alveolar Bone Width at the First and Second Maxillary Premolars in Healthy
Patients: A Cone Beam Computed Tomography Study.
AB - The purpose of this study was to analyze the thickness of the facial alveolar
bone at the first and second maxillary premolars and determinate the percentage
of premolars that reached 2 mm in width. A retrospective study was performed,
analyzing cone beam computed tomography scans from the database of the Oral
Surgery Unit of the University of Valencia. Patients with periodontal disease,
orthodontic treatment, absence among the first maxillary molars, premolars with
endodontic treatment, or prosthetic restorations were excluded. The facial
alveolar bone width was measured at 1, 2, 3, and 5 mm apical to the vestibular
bone peak. A total of 44 patients were included in the study, with 72 first
premolars and 72 second premolars analyzed. A descriptive analysis was performed
and the normal means were assessed using the Kolmogorov-Smirnov test. The average
width of the facial alveolar bone at first and second maxillary premolars was
respectively: 1.41 +/- 0.50 and 1.72 +/- 0.56 at 1 mm, 1.68 +/- 0.72 and 2.23 +/-
0.66 at 2 mm, 1.71 +/- 0.89 and 2.43 +/- 0.82 at 3 mm, 1.44 +/- 1.00 and 2.31 +/-
1.06 at 5 mm from the vestibular bone peak. The facial alveolar bone width at the
second maxillary premolars was greater than at the first maxillary premolars at
all points measured. This information should be taken in account when planning
immediate implants. Further studies are needed to analyze bone resorption at
maxillary premolars to better understand facial alveolar bone width influence in
implant treatment.
PMID- 28421874
TI - Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate
mixture/oxycodone transdermal patch system: a Phase I study.
AB - AIM: To characterize the pharmacokinetic profile and evaluate the safety and
tolerability of a transdermal oxycodone patch containing tocopheryl phosphate
mixture (TPM). PATIENTS & METHODS: Eleven healthy subjects received a single
application of three TPM/oxycodone patches applied to the torso for 72 h.
RESULTS: Oxycodone was detected 8.0 +/- 2.7-h postpatch administration, reaching
a mean maximum plasma concentration of 3.41 +/- 1.34 ng/ml at 49.3 +/- 21.2 h.
The safety profile was consistent with the application method and known side
effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation
was observed. CONCLUSION: A 3-day application of the TPM/oxycodone patch
demonstrated an acceptable safety profile and was well tolerated by healthy
subjects, with limited dermal irritation following application.
PMID- 28421875
TI - Three-Dimensional Printing and Its Applications in Otorhinolaryngology-Head and
Neck Surgery.
AB - Objective Three-dimensional (3D)-printing technology is being employed in a
variety of medical and surgical specialties to improve patient care and advance
resident physician training. As the costs of implementing 3D printing have
declined, the use of this technology has expanded, especially within surgical
specialties. This article explores the types of 3D printing available, highlights
the benefits and drawbacks of each methodology, provides examples of how 3D
printing has been applied within the field of otolaryngology-head and neck
surgery, discusses future innovations, and explores the financial impact of these
advances. Data Sources Articles were identified from PubMed and Ovid MEDLINE.
Review Methods PubMed and Ovid Medline were queried for English articles
published between 2011 and 2016, including a few articles prior to this time as
relevant examples. Search terms included 3-dimensional printing, 3 D printing,
otolaryngology, additive manufacturing, craniofacial, reconstruction, temporal
bone, airway, sinus, cost, and anatomic models. Conclusions Three-dimensional
printing has been used in recent years in otolaryngology for preoperative
planning, education, prostheses, grafting, and reconstruction. Emerging
technologies include the printing of tissue scaffolds for the auricle and nose,
more realistic training models, and personalized implantable medical devices.
Implications for Practice After the up-front costs of 3D printing are accounted
for, its utilization in surgical models, patient-specific implants, and custom
instruments can reduce operating room time and thus decrease costs. Educational
and training models provide an opportunity to better visualize anomalies,
practice surgical technique, predict problems that might arise, and improve
quality by reducing mistakes.
PMID- 28421876
TI - Congenital tuberculosis: case report and review of the literature.
AB - Congenital tuberculosis is rare, even where tuberculosis (TB) is endemic. A 14
day-old girl presented with a 3-day history of fever and respiratory distress.
Her mother was diagnosed with a disseminated TB infection immediately after the
delivery which was confirmed by a positive TB-polymerase chain reaction (TB-PCR)
and subsequent culture from ascites and sputum. The infant was separated from her
mother at birth. Her chest radiograph showed bilateral miliary nodules.
Congenital TB was strongly suspected because of the symptoms, signs and maternal
TB history, and was confirmed by TB-PCR and culture from the gastric lavage.
Timely administration of standard anti-TB therapy resulted in a good outcome. The
case highlights the importance of maternal TB history and typical miliary pattern
on chest radiography for early diagnosis of congenital or neonatal TB which in
turn facilitates prompt treatment and the prognosis.
PMID- 28421877
TI - Biomarkers in adult posthemorrhagic hydrocephalus.
AB - Posthemorrhagic hydrocephalus is a severe complication following intracranial
hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity
and mortality and serves as an important clinical predictor of adverse outcomes
after intracranial hemorrhage. Currently, no effective medical intervention
exists to improve functional outcomes in posthemorrhagic hydrocephalus patients
because little is still known about the mechanisms of posthemorrhagic
hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic
hydrocephalus pathogenesis would facilitate development of clinical treatments,
this is an active research area. The purpose of this review is to describe recent
progress in elucidation of molecular mechanisms that cause posthemorrhagic
hydrocephalus. What we are certain of is that the entry of blood into the
ventricular system and subarachnoid space results in release of lytic blood
products which cause a series of physiological and pathological changes in the
brain. Blood components that can be linked to pathology would serve as disease
biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are
known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus
progression. These findings suggest that modulation of biomarker expression or
function may benefit posthemorrhagic hydrocephalus patients.
PMID- 28421878
TI - Cerebrovascular injury in cryptococcal meningitis.
AB - Background Cryptococcal meningitis continues to be one of the common causes of
chronic central nervous system infection worldwide. Individuals with cryptococcal
meningitis can occasionally present with small vessel vasculitis causing infarcts
primarily in the basal ganglia, internal capsule, and thalamus. Literature
regarding patterns of cerebrovascular injury among patients with cryptococcal
meningitis is scanty, and outcome following these vascular involvements is
unknown. Aim To study the clinical profile, imaging findings, and details of
vascular territory involved among patients admitted with cryptococcal meningitis
and central nervous system infarct in a tertiary care center from India. And to
compare the outcomes of patients of cryptococcal meningitis with or without
central nervous system infarcts in terms of mortality and morbidity, Methodology
A total of 151 patients with microbiologically proven cryptococcal meningitis
over a time span of 11 years were retrospectively enrolled into the study. Of
these, 66 patients met the inclusion criteria of having appropriate imaging of
the brain. The presence of infarct in the imaging was analyzed by two independent
radiologists. Patterns of central nervous system involvement and types of
vascular injury were ascertained based on radiological parameters. Clinical
parameters and outcomes of patients with and without infarcts were compared.
Results Twenty (13%) of these patients had evidence of central nervous system
infarcts on imaging. The mean age of patients with and without infarcts was 41
years and 38 years, respectively. Male predominance was present among both the
groups. The presence of fever, neck stiffness, positive blood culture, and
hydrocephalus in central nervous system imaging was similar among patients with
or without infarct. Longer duration of illness, low sensorium at the time of
presentation, low Glasgow Coma Scale score, presence of meningeal inflammation,
cryptococcomas, and basal exudates in imaging were higher in patients with
infarct. All the infarcts were of the lacunar type. Sixty percent of the
cerebrovascular infarcts were acute in nature, 50% of these being multiple.
Unilateral infarcts were seen in 70% of the patients. The most common site of
infarct was the basal ganglia, others being distributed over the thalamus,
frontal, temporal, parieto-occipital regions in the descending order. The
presence of neurovascular involvement in the form of infarcts to the risk of
morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively.
Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare
entity. These tend to present as multiple lacunar infarcts. Mortality and
morbidity associated with these patients is higher when compared to patients who
do not have infarcts. This result suggests that vascular injury plays a role in
predicting outcome of patients with cryptococcal meningitis. Future studies are
needed to understand the mechanism by which vascular events (infarcts) occur and
result in poor outcome.
PMID- 28421879
TI - DNA methylation mechanism of intracellular zinc deficiency-induced injury in
primary hippocampal neurons in the rat brain.
AB - OBJECTIVE: To explore Zn2+ deficiency-induced neuronal injury in relation to DNA
methylation, providing valuable data and basic information for clarifying the
mechanism of Zn2+ deficiency-induced neuronal injury. METHODS: Cultured
hippocampal neurons were exposed to the cell membrane-permeant Zn2+ chelator
N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) (2 MUM), and to TPEN
(2 MUM) plus ZnSO4 (5 MUM) for 24 hours. We analyzed intracellular Zn2+ levels,
neuronal viability, and protein/mRNA levels for DNA (cytosine-5)
methyltransferase 1 (DNMT1), DNA (cytosine-5-) methyltransferase 3 alpha
(DNMT3a), methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor
(BDNF), and growth arrest and DNA-damage-inducible, beta (GADD45b) in the treated
neurons. RESULTS: We found that exposure of hippocampal neurons to TPEN (2 MUM)
for 24 hours significantly reduced intracellular Zn2+ concentration and neuronal
viability. Furthermore, DNMT3a, DNMT1, BDNF, and GADD45b protein levels in TPEN
treated neurons were significantly downregulated, whereas MeCP2 levels were, as
expected, upregulated. In addition, DNMT3a and DNMT1 mRNA levels in TPEN-treated
neurons were downregulated, while MeCP2, GADD45b, and BDNF mRNA were largely
upregulated. Addition of ZnSO4 (5 MUM) almost completely reversed the TPEN
induced alterations. CONCLUSION: Our data suggest that free Zn2+ deficiency
induced hippocampal neuronal injury correlates with free Zn2+ deficiency-induced
changes in methylation-related protein gene expression including
DNMT3a/DNMT1/MeCP2 and GADD45b, as well as BDNF gene expression.
PMID- 28421880
TI - Interactive dynamics among therapist interventions, therapeutic alliance and
metacognition in the early stages of the psychotherapeutic process.
AB - OBJECTIVE: Several authors have identified a bidirectional link between patient
metacognitive functioning and the therapeutic alliance. Specifically,
metacognition might be enhanced by a positive alliance with the clinician,
whereas metacognitive deficits might impede the alliance. Interestingly, the
therapist's technical interventions might influence both therapeutic alliance and
metacognitive functioning. However, little is known about the interactions
between these dimensions. The aim of the present study is to explore these
interactions more fully in the earliest phase of the therapeutic process. METHOD:
Participants included 24 patients and 12 therapists in training. The
Metacognition Assessment Scale-Revised, Collaborative Interaction Scale, and
Psychodynamic Intervention Rating Scale were employed in the first three sessions
of psychotherapy. RESULTS: Sequential analyses revealed that different therapist
interventions co-occurred with three different levels of the therapeutic
alliance: A first level characterized by a positive collaboration, a second
characterized by a neutral collaboration, and a third characterized by ruptures.
Importantly, the patient's metacognitive functioning was found to mediate the
relationship between the therapeutic intervention and the therapeutic alliance in
the positive and neutral levels of collaboration but not in the ruptures one.
CONCLUSIONS: These findings suggest that a specific interdependence exists among
the therapeutic alliance, technical intervention, and metacognitive functioning.
Clinical or methodological significance of this article: From a methodological
standpoint, the originality of the present study lies in the combination of an
interactionist approach, which conceives process factors as interrelated
dimensions interacting in non-additive and often nonlinear ways, with analyses at
both micro- and macro-analytic levels (i.e., sequential and mediation analyses).
From a theoretical standpoint, findings of the present study indicate that
specific therapist's interventions are related to specific levels of the
therapeutic alliance (i.e., positive, neutral and negative), hence providing
crucial insights into the clinical understanding of the psychotherapy process.
PMID- 28421881
TI - Factors pivotal for designing of nanoantimicrobials: an exposition.
AB - Understanding the interplay between bacterial pathogens and antimicrobials is a
key to realize the control over infections causing morbidity and mortality. An
important current issue of contemporary medicine and microbiology is the search
for new strategies for adequate therapy of infectious diseases associated with
rapidly emerging multidrug-resistant (MDR) pathogens. Recently, a great deal of
progress has been made in the field of nanobiotechnology towards the development
of various nanoantimicrobials (NAMs) as novel therapeutic solution. Current
microbiological studies, employing either synthetic antibiotics or natural
antimicrobial, have demonstrated the ability of NAMs to tackle the issue of MDR
by reverting the mechanisms of resistance. The present review critically
discusses the various factors that can contribute to modulate the effects of NAMs
on microbes. It includes essential features of NAMs including but not limited to
composition, surface charge, loading capacity, size, hydrophobicity/philicity,
controlled release and functionalization. In contrast, how microbial structural
differences, biofilm formation, persister cells and intracellular pathogens
contribute towards sensitivity or resistance towards antimicrobials is
comprehensively analysed. These multilateral factors should be considered
earnestly in order to make NAMs a successful alternative of the conventional
antibiotics.
PMID- 28421882
TI - Inhibition of HER3 activation and tumor growth with a human antibody binding to a
conserved epitope formed by domain III and IV.
AB - Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged
as relevant target for antibody-mediated tumor therapy. Here, we describe a novel
human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and
parts of domain IV of the extracellular region of HER3, conserved between HER3
and mouse ErbB3. An affinity of 11 nM was determined for the monovalent
interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with
subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50
values in the low picomolar range (27 - 83 pM). The antibody competed with
binding of heregulin to HER3-expressing cells, efficiently inhibited
phosphorylation of HER3 as well as downstream signaling, and induced receptor
internalization and degradation. Furthermore, IgG 3-43 inhibited heregulin
dependent proliferation of several HER3-positive cancer cell lines and heregulin
independent colony formation of HER2-overexpressing tumor cell lines.
Importantly, inhibition of tumor growth and prolonged survival was demonstrated
in a FaDu xenograft tumor model in SCID mice. These findings demonstrate that by
binding to the membrane-proximal domains III and IV involved in ligand binding
and receptor dimerization, IgG 3-43 efficiently inhibits activation of HER3,
thereby blocking tumor cell growth both in vitro and in vivo.
PMID- 28421883
TI - CTSA Institution Responses to Proposed Common Rule Changes: Did They Get What
They Wanted?
AB - In 2015, the U.S. Department of Health and Human Services (HHS) and 15 other
federal departments and agencies proposed revisions to the Federal Policy for the
Protection of Human Subjects. In this Notice of Proposed Rulemaking (NPRM), the
departments sought to strengthen, modernize, and make more effective human
subjects regulations while reducing administrative burden, delay, and ambiguity.
We reviewed public comments from National Institutes of Health (NIH)-funded
Clinical and Translational Science Awards (CTSA) institutions on key provisions
of the NPRM to understand how the proposed changed were received at research
intensive institutions. CTSA institutions responding to the proposed rule were
predominantly opposed to the major proposals, including proposed changes to the
treatment of de-identified biospecimens, demonstrating a lack of support from
academic medical centers. In January 2017, a Final Rule was issued. We compare
the Final Rule to what was proposed.
PMID- 28421884
TI - Children's Decision-Making Involvement About Research Participation: Associations
With Perceived Fairness and Self-Efficacy.
AB - The primary objective of this study was to examine the associations of children's
involvement in decisions about research participation with their perceptions of
the decision-making process and self-efficacy. Participants were children (ages 8
17) who enrolled in research studies in the prior 2 months. Children completed a
questionnaire that yielded three decision-making involvement subscales:
Researcher Engages Child, Researcher Supports Autonomy, and Child Participates.
Children reported on fairness of the decision-making process and health-related
decision self-efficacy. After adjusting for age, higher scores on Researcher
Engages Child were associated with greater self-efficacy, and higher scores on
Researcher Supports Autonomy were associated with greater perceived fairness.
These data underscore the potential importance of researcher-child interactions
about research participation when assent is sought, including proactively
involving children in the decision by asking for their opinions and communicating
their central role in the decision, which are likely to be more meaningful to
children than receiving information or signing a form.
PMID- 28421885
TI - Recognizing Risk and Vulnerability in Research Ethics: Imagining the "What Ifs?"
AB - Research ethics committees (RECs) may misunderstand the vulnerability of
participants, given their distance from the field. What RECs identify as the
vulnerabilities that were not adequately recognized in protocols and how they
attempt to protect the perceived vulnerability of participants and mitigate risks
were examined using the response letters sent to researchers by three university
based RECs. Using a critical qualitative method informed by feminist ethics, we
identified an overarching theme of recognizing and responding to cascading
vulnerabilities and four subthemes: identifying vulnerable groups, recognizing
potentially risky research, imagining the "what ifs," and mitigating perceived
risks. An ethics approach that is up-close, as opposed to distant, is needed to
foster closer relationships among participants, researchers, and RECs and to
understand participant vulnerability and strength better.
PMID- 28421888
TI - Instructions to Prospective Authors by Indian Biomedical Journals: An Opportunity
to Promote Responsible Conduct of Research.
AB - Journals provide instructions to prospective authors to facilitate the process of
manuscript publication. The information provided under such instructions could be
a potential opportunity to promote responsible conduct of research (RCR). We
analyzed 74 Indian biomedical journals for the type of information provided in
the "instructions to authors" section and adherence to the International
Committee of Medical Journal Editors (ICMJE) recommendations. Among the 71
journals that had an "instructions to authors" section, 53 journals adhered to
ICMJE recommendations. We discuss sections of the ICMJE recommendations detailed
by Indian biomedical journals under the "instructions to authors" section and
emphasize components that require greater exposure.
PMID- 28421887
TI - Preferences for the Return of Individual Results From Research on Pediatric
Biobank Samples.
AB - Discussions about disclosing individual genetic research results include calls to
consider participants' preferences. In this study, parents of Boston Children's
Hospital patients set preferences for disclosure based on disease preventability
and severity, and could exclude mental health, developmental, childhood
degenerative, and adult-onset disorders. Participants reviewed hypothetical
reports and reset preferences, if desired. Among 661 participants who initially
wanted all results (64%), 1% reset preferences. Among 336 participants who
initially excluded at least one category (36%), 38% reset preferences.
Participants who reset preferences added 0.9 categories, on average; and their
mean satisfaction on 0 to 10 scales increased from 4.7 to 7.2 ( p < .001). Only
2% reduced the number of categories they wanted disclosed. Findings demonstrate
the benefits of providing examples of preference options and the tendency of
participants to want results disclosed. Findings also suggest that preference
setting models that do not provide specific examples of results could
underestimate participants' desires for information.
PMID- 28421889
TI - Overall Assessment of Human Research and Ethics Committees in the United Arab
Emirates.
AB - Growing demand for human health research in the United Arab Emirates (UAE) has
prompted the need to develop a robust research ethics oversight. Examination of
the structure, function, and practices of the human research ethics committees
(HRECs), followed by evaluation of standards for measuring research output, was
conducted. Results indicate that among the HRECs, 90% followed International
Council for Harmonization-Good Clinical Practice guidelines, 66.6% have been in
operation for more than 5 years, 95% reviewed proposals within 8 weeks, and 56%
reviewed for scientific merit apart from ethics. However, systems to recognize
accomplishments of researchers, funding transparency, and adverse event reporting
were deployed in less than 30% of all HRECs. Research was incorporated into the
vision and mission statements of many (65%) organizations. Research publications,
collaborations, and recognitions were used to measure research output and report
key performance indicators. In spite, resources to generate research output such
as dedicated budget (20%), support staff (20%), and continuous training and
mentoring program for medical residents (15%) and HREC members (25%) were somehow
lacking. HREC structure and operations in the UAE are similar to other regions of
the world. Systems to conduct research and report outcomes are defined in the
UAE. Regulatory legislation and allocation of resources to support the clinical
research enterprise will not only help to meet growing demand for clinical trials
but also transform the quality of patient care in the UAE. It is anticipated that
the results of this study will benefit investigators, regulators, pharmaceutical
sponsors, and the policy makers in the region.
PMID- 28421890
TI - Inmate Health Care Provided in an Emergency Department.
AB - The United States has the highest rate of incarceration in the world. Many
correctional facilities have outsourced the medical care for this population that
often presents with complex health issues. This study evaluates the reasons that
inmates present to an emergency department (ED) and compares them to the general
population ED visits. The most common presenting complaints were trauma (16.8%),
abdominal pain (13.5%), chest pain (9.0%), and self-injury (8.7%). These
presenting complaints differed significantly from those of the general population
(abdominal pain [8.1%] and chest pain [5.2%]). Inmate-patients seen in the ED
presented with a significantly higher frequency of trauma, 16.8% versus
approximately 1.5%.
PMID- 28421891
TI - Truth Be Told: Evaluation of a Narrative and Skills Intervention in Two Women's
Prisons.
AB - This article describes the evaluation of a narrative and skills intervention to
enable women to come to terms with their offenses, tell the truth, and then work
to deal with the emotions and issues surrounding their offenses, in two southern
U.S. women's prisons. The intervention involved skills building in communication,
community building, creativity, and caring for the self, using narrative writing,
speaking, and movement. There was broad agreement that the intervention had
multiple positive impacts, including insight into factors that lead to
incarceration, comfort with selves and better ability to express themselves,
restorative justice (ability to understand the situation of others, understanding
the impact on themselves and their families), better relationships with other
inmates, and understanding the challenges that may lead to recidivism. Findings
are consistent with the importance of "confession" and the importance of
narrative in traumatic life situations in bringing resolution.
PMID- 28421892
TI - Editor's Letter.
PMID- 28421893
TI - Journal of Correctional Health Care.
PMID- 28421894
TI - How learning analytics can early predict under-achieving students in a blended
medical education course.
AB - AIM: Learning analytics (LA) is an emerging discipline that aims at analyzing
students' online data in order to improve the learning process and optimize
learning environments. It has yet un-explored potential in the field of medical
education, which can be particularly helpful in the early prediction and
identification of under-achieving students. The aim of this study was to identify
quantitative markers collected from students' online activities that may
correlate with students' final performance and to investigate the possibility of
predicting the potential risk of a student failing or dropping out of a course.
METHODS: This study included 133 students enrolled in a blended medical course
where they were free to use the learning management system at their will. We
extracted their online activity data using database queries and Moodle plugins.
Data included logins, views, forums, time, formative assessment, and
communications at different points of time. Five engagement indicators were also
calculated which would reflect self-regulation and engagement. Students who
scored below 5% over the passing mark were considered to be potentially at risk
of under-achieving. RESULTS: At the end of the course, we were able to predict
the final grade with 63.5% accuracy, and identify 53.9% of at-risk students.
Using a binary logistic model improved prediction to 80.8%. Using data recorded
until the mid-course, prediction accuracy was 42.3%. The most important
predictors were factors reflecting engagement of the students and the consistency
of using the online resources. CONCLUSIONS: The analysis of students' online
activities in a blended medical education course by means of LA techniques can
help early predict underachieving students, and can be used as an early warning
sign for timely intervention.
PMID- 28421895
TI - Metastatic Pulmonary Angiosarcoma Presenting With Bilateral Secondary Spontaneous
Pneumothoraces.
AB - BACKGROUND: Spontaneous pneumothorax (SP) is uncommon and can present as a
primary disease process or as a result of underlying lung pathology. Several
parenchymal lung diseases, such as malignancy, are known to cause SP. One such
malignancy, angiosarcoma, has a high propensity to metastasize to the lung and
present as cavitary and cystic lesions. CASE: We present a case of a 76-year-old
male diagnosed with angiosarcoma of the scalp that was found to have extensive
cystic pulmonary metastatic lesions. Soon after his initial diagnosis, he
presented with severe respiratory distress secondary to a spontaneous left-sided
pneumothorax. After intubation and left-sided chest tube placement, the patient
developed a right-sided tension pneumothorax requiring emergent chest tube
placement. CONCLUSION: Cutaneous angiosarcoma is a rare malignancy that
frequently metastasizes the lung. Spontaneous pneumothorax can be the presenting
manifestation of the disease and often results in respiratory failure.
PMID- 28421896
TI - Anosognosia and Its Relation to Psychiatric Symptoms in Early-Onset Alzheimer
Disease.
AB - BACKGROUND: We investigated differences in the prevalence of anosognosia and
neuropsychiatric symptoms (NPSs) characteristics according to disease severity in
patients with early-onset Alzheimer disease (EOAD). METHODS: We recruited 616
patients with EOAD. We subdivided participants into 2 groups based on the
presence or absence of anosognosia and then again by Clinical Dementia Rating
(CDR) scale. We compared the differences in the Neuropsychiatric Inventory (NPI)
scores according to anosognosia and disease severity. RESULTS: The percentage of
patients with anosognosia in each CDR group steadily increased as the CDR rating
increased (CDR 0.5 8.6% vs CDR 1 13.6% vs CDR 2 26.2%). The NPI total score was
significantly higher in patients with anosognosia in the CDR 0.5 and 1 groups; by
contrast, it had no association in the CDR 2 group. Frontal lobe functions were
associated with anosognosia only in the CDR 0.5 and 1 groups. After
stratification by CDR, in the CDR 0.5 group, the prevalence of agitation ( P =
.040) and appetite ( P = .013) was significantly higher in patients with
anosognosia. In the CDR 1 group, patients with anosognosia had a significantly
higher prevalence of delusions ( P = .032), hallucinations ( P = .048), and sleep
disturbances ( P = .047). In the CDR 2 group, we found no statistical difference
in the frequency of symptoms between patients with and without anosognosia.
CONCLUSION: These results confirm that the prevalence of anosognosia as well as
the individual NPS and cognitive functions associated with it differ according to
EOAD severity.
PMID- 28421897
TI - Negative Bias in the Perception and Memory of Emotional Information in Alzheimer
Disease.
AB - BACKGROUND: There is some controversy about the ability of patients with
Alzheimer disease (AD) to experience and remember emotional stimuli. This study
aims to assess the emotional experience of patients with AD and the existence of
emotional enhancement of memory. We also investigated the influence of affective
state on these processes. METHODS: Sixty pictures from the International
Affective Picture System were administered to 106 participants (72 patients with
AD and 54 controls). Participants performed immediate free recall and recognition
tasks. Positive and Negative Affect Schedule was used to assess the participants'
current affect. RESULTS: Patients identified the valence of unpleasant pictures
better than of others pictures and experienced them as more arousing. Patients
and controls recalled and recognized higher number of emotional pictures than of
neutral ones. Patients discriminated better the unpleasant pictures. A mood
congruent effect was observed on emotional experience but not on memory. Positive
affect was associated with better immediate recall and with a more liberal
response bias. CONCLUSION: Patients with AD can identify the emotional content of
the stimuli, especially of the unpleasant ones, and the emotional enhancement of
memory is preserved. Affective state does not explain the differences in the
processing and memory of emotional items between patients and controls.
PMID- 28421899
TI - Prolapse of the bladder through a vesicovaginal fistula.
PMID- 28421900
TI - The magnitude and factors related to facility-based maternal mortality in
Mozambique.
AB - Facility-based maternal mortality remains an important public health problem in
Mozambique. A number of factors associated with health system functioning can be
described behind the occurrence of these deaths. This paper aimed to evaluate the
magnitude of the health facility-based maternal mortality, its geographical
distribution and to assess the health facility factors implicated in the
occurrence of these deaths. A secondary analysis was done on data from the survey
on maternal health needs performed by the Ministry of Health of Mozambique in
2008. During the study period 2.198 maternal deaths occurred out of 312.537
deliveries. According to the applied model the availability of Maternal and Child
Health (MCH) nurses performing Emergency Obstetric Care functions was related to
the reduction of facility-based maternal mortality by 40%. No significant effects
were observed for the availability of medical doctors, surgical technicians and
critical delivery room equipment. Impact statement Is largely known that the
availability of skilled attendants assisting every delivery and providing
Emergency Obstetric Care services during the pregnancy, labor and Childbirth is
key for maternal mortality reduction. This study add the differentiation on the
impact of different cadres of health services providers working on maternal and
child health services on the facility based maternal mortality. In this setting
the study proven the high impact of the midlevel skilled maternal and child
health nurses on the reduction of maternal mortality. Another important add from
this study is the use of facility based maternal mortality data to inform the
management process of maternal healthcare services. The findings from this study
have potential to impact on the decision of staffing prioritization in setting
like the study setting. The findings support the policy choice to improve the
availability of maternal and child health nurses.
PMID- 28421898
TI - Targeting the nuclear RNA exosome: Poly(A) binding proteins enter the stage.
AB - Centrally positioned in nuclear RNA metabolism, the exosome deals with virtually
all transcript types. This 3'-5' exo- and endo-nucleolytic degradation machine is
guided to its RNA targets by adaptor proteins that enable substrate recognition.
Recently, the discovery of the 'Poly(A) tail exosome targeting (PAXT)' connection
as an exosome adaptor to human nuclear polyadenylated transcripts has relighted
the interest of poly(A) binding proteins (PABPs) in both RNA productive and
destructive processes.
PMID- 28421901
TI - BMI at early puerperium: Body image, eating attitudes and mood states.
AB - The present study was aimed to verify if body weight could influence self
perception, in terms of body image, mood states, dissatisfaction with physical
appearance and risk of eating disorders. In particular, we evaluated the
differences between women of normal weight vs. overweight and obese during the
delicate phase of puerperium to verify if there were different emotional
structures, linked to BMI. Thirty-two women, 16 normal-weight and 16 overweight
or obese, belonging to the Department of Obstetrics and Gynaecology of the
University Hospital, were individually interviewed. The Body Uneasiness Test
(BUT), the Eating Disorder Inventory (EDI) and the Profile of Mood States (POMS)
were used for the evaluation. Findings showed that the BMI in puerperium is
significantly correlated to mood states and body perception. Furthermore,
significant differences emerged in eating attitudes and behaviours, in specific
aspects related to the weight gain phobia and the body shape perception, symptoms
classically associated with the risk of developing an eating disorder.
PMID- 28421902
TI - The role of ovarian reserve markers in prediction of clinical pregnancy.
AB - To evaluate the role of ovarian reserve markers in the prediction of clinical
pregnancy and embryo transfer accomplishment among poor responder IVF applicants.
304 female poor responder IVF applicants were included in this prospective cohort
study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF
outcomes were compared in pregnant and non-pregnant groups as well as in ET vs.
non-ET groups. The number of retrieved oocytes was significantly correlated
positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH
and AFC were similar to the rate of pregnancy. Quartiles of AMH (<25%/25-75% and
<25%/>75%) were statistically significant. Mean serum levels for AMH were
significantly lower in the non-ET group. Our findings seem to indicate that day 3
AMH values can predict ET accomplishment with a sensitivity of 96% and a
specificity of 35%. Quartiles of AMH <25% (< 0.21 ng/mL) can predict the IVF
results among poor responder IVF applicants. Impact statement Various cut-off
values have been determined for day 3 serum AMH values. These values help to
determine the groups that are expected to give normal, high or low response to
stimulation and decide the treatment options. In contrast to other groups of
patients, poor responders cannot reach the embryo transfer stage for several
reasons. These are; absence of a mature oocyte after oocyte pick-up,
fertilisation failure without male factor or poor embryo quality. In the present
study; a cut-off value of 0.33 ng/mL for the prediction of ET accomplishment in
poor responder patients was determined with a sensitivity of 96%. Additionally,
clinical pregnancy could not be achieved under the value of 0.21 ng/mL day 3 AMH
values. It is important to clarify the embryo transfer success of poor responder
patients prior to expected treatment success. Pre-treatment counselling for these
patients would lessen the disappointment that may develop after treatment. The
cost-effectiveness of treatments below these AMH values can be determined by
further studies.
PMID- 28421903
TI - Expression of matrix metalloproteinase-9 and its substrate level in patients with
premature rupture of membranes.
AB - In this study, 30 case of patients with full-term premature membrane rupture and
another 30 cases of full-term delivered subject without premature rupture of
membranes (PROM) were selected to explore the relationship between premature
membrane rupture with matrix metalloproteinase 9 (MMP-9) and its substrate level.
Results showed the plasma zinc, MMP-9 in serum and amniotic fluid increased in
patients with PROM; their type IV collagen in serum and foetal membrane
decreased. Increased Zinc ion concentration results in increased concentration of
MMP-9, a zinc-dependent enzyme; the degradation of type IV collagen by MMP-9
might be the potential mechanism of premature rupture of membranes in full-term
pregnant women.
PMID- 28421904
TI - Effects of 1alpha, 25-dihydroxyvitamin D3 on programmed cell death of Ishikawa
endometrial cancer cells through ezrin phosphorylation.
AB - This study investigated the effects of 1alpha, 25-dihydroxyvitamin D3-induced
cell death and its underlying molecular mechanisms in Ishikawa endometrial
carcinoma cells. The effects of 1alpha, 25-dihydroxyvitamin D3 on Ishikawa cells
were examined by 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyl-tetrazolium bromide,
thiazolyl blue (MTT) assay. 1alpha, 25-dihydroxyvitamin D3 was shown to induce
programmed cell death in Ishikawa endometrial carcinoma cells by activation of
caspase-3 and caspase-9, along with elevation of Bcl-2 and Bcl-xL. Cell viability
was reduced by 1alpha, 25-dihydroxyvitamin D3 in a concentration-dependent manner
up to 2.5 MUM. In addition, ezrin phosphorylation increased with the 1alpha, 25
dihydroxyvitamin D3 concentration (0-0.5 MUM). The protein level of caspase-9 was
increased by 1alpha, 25-dihydroxyvitamin D3 up to 0.5 MUM. This is the first
report regarding the efficacy and molecular mechanisms underlying the effects of
1alpha, 25-dihydroxyvitamin D3 in endometrial cancer cells. Our findings indicate
that 1alpha, 25-dihydroxyvitamin D3 induces endometrial cancer cell death in a
concentration-dependent manner. Impact statement Up to date, there is no report
about the efficacy and molecular underlying mechanisms on the effect of vitamin
D3 in endometrial cancer cells. Our findings indicate that 1alpha, 25
dihydroxyvitamin D3. which is an active metabolite of vitamin D3, induces
Ishikawa endometrial cancer cell death in a concentration-dependent manner by
activation of caspase-3 and -9, along with elevation of Bcl-2 and Bcl-xL. In
addition, the same concentration of 1alpha, 25-dihydroxyvitamin D3 that provoked
apoptotic signals caused phosphorylation of ezrin at threonine 567 in a VDR
dependent manner. This study suggests that 1alpha, 25-dihydroxyvitamin D3 within
the optimal range (0.5 uM) would induce apoptosis through Fas-ezrin-caspase-3,
8, -9 signalling axis which may be a critical cell death regulator in Ishikawa
endometrial cancer cell. Further study will be more interesting to address
molecular connections or prove this critical optimal concentration range of
vitamin D.
PMID- 28421905
TI - Ultrasonic elastography exploration of the foetal brain: A case of atypical
choroid plexus papilloma.
PMID- 28421906
TI - The role of para-aortic lymphadenectomy in stage IIIC endometrial cancer: A
single-institute study.
AB - The therapeutic value of para-aortic lymphadenectomy (PAL) in women with
endometrial cancer (EC) remains uncertain. We retrospectively analysed 25
patients with stage IIIc EC (17 stage IIIC1; 8 IIIC2) who were treated in our
institution. All subjects had undergone pelvic lymphadenectomies in which para
aortic nodes were sampled, or removed only when these nodes were enlarged.
Sampling of para-aortic nodes or PAL was performed in all patients with stage
IIIC2 disease and one of 17 with stage IIIC1 disease. Para-aortic lymph nodes
were the most frequent site of recurrence in stage IIIC1 patients, but no such
recurrences occurred in stage IIIC2 patients. Overall survival tended to be
shorter in stage IIIC1 patients than stage IIIC2 patients. Our findings indicate
that PAL improves the outcomes of patients with EC and high risk of para-aortic
lymph node metastasis, such as those with positive pelvic lymph nodes or
enlargement of para-aortic lymph nodes. Impact statement Para-aortic lymph node
(PALN) metastases are important prognostic factors in endometrial cancer. Overall
survival of patients with stage IIIC1 disease is generally longer than for those
with stage IIIC2 disease. Retrospective studies - but no prospective studies -
have suggested that para-aortic lymphadenectomy (PAL) provides a survival
benefit. In our institution, we had performed PAL or para-aortic sampling for
patients with enlarged PALNs; therefore, as most IIIC1 patients had no enlarged
PALNs, they underwent pelvic lymphadenectomy only, whereas all IIIC2 patients had
enlarged PALNs and underwent pelvic lymphadenectomy and PAL or PALN sampling in
addition to pelvic lymphadenectomy. However, under this policy, survival of stage
IIIC1 patients was not better than for stage IIIC2 patients. Our retrospective
study indicates a survival benefit for PAL in patients with pelvic node-positive
or enlarged PALN. PAL warrants a prospective randomised trial to see whether it
should be a standard treatment in these patients.
PMID- 28421907
TI - A review of the open laparoscopic Hasson technique and retrieval of adnexal
specimen via umbilicus.
AB - Laparoscopic entry techniques vary amongst surgeons and gynaecologists, with
gynaecologists favouring Veress needle entry. Recent RCOG/BSGE recommendations
have recommended retrieval of ovarian masses via the umbilical port with
resultant less postoperative pain and a faster retrieval time than with retrieval
through lateral ports of the same size. This is a prospective observational study
reviewing the Hasson entry technique and the introduction of retrieval of
specimens via the umbilicus in patients scheduled for a laparoscopy procedure at
our day surgery unit. We found no immediate or major surgical complications and
all specimens were successfully retrieved through the umbilicus. Pain scores were
low. We recommend the technique for extirpative gynaecological surgery. Impact
Statement This study confirms that conversion from the closed Veress to the open
Hasson technique is achievable in a university hospital setting. Operator
confidence during the learning phase is enhanced by the use of ultrasound to
locate and measure the depth of the umbilical ligament. Retrieval of benign
adnexal specimens through the umbilicus was very satisfactory.
PMID- 28421908
TI - Extravasating uterine pseudoaneurysm: A rare cause of postpartum haemorrhage.
AB - Postpartum haemorrhage (PPH) remains one of the leading causes of maternal death
worldwide and can be classified as either immediate (primary) or delayed
(secondary) according to the onset time - before or after 24 hours postpartum.
Uterine pseudoaneurysm is a rare cause of PPH that has been suggested to arise
from abnormal vascular regression and a recurrent vascular healing state, such as
a vascular stricture and relaxation with thrombin deposits after placental
expulsion. With advances in multidetector computed tomography, 3D-computed
tomography with angiography can aid in identifying the location and originating
vessels of the pseudoaneurysm via fast and clear 3D images. Once a bleeding
pseudoaneurysm is diagnosed as the cause of PPH, conservative management is
frequently unsuccessful in controlling bleeding. Transcatheter uterine arterial
embolisation appears to be the treatment of choice in haemodynamically stable
women.
PMID- 28421909
TI - Management of intra-abdominally translocated contraceptive devices, is surgery
the only way to treat this problem?
AB - This study was a multi-centre retrospective review of patients with uterine
perforation caused by intrauterine contraceptive devices (IUDs). A total of 15
patients were registered, in a seven year period. Among them, five were
asymptomatic and the rest were symptomatic. Asymptomatic patients were managed
conservatively, except in one case in which the patient requested surgery because
she also wanted a tubal ligation. Symptomatic patients all underwent surgery. All
the surgeries were elective and all the surgical procedures were initiated
laparoscopically. There were seven complications in the surgically managed group:
conversion to laparotomy (n = 3), bowel injury (n = 2), bladder injury (n = 1),
and wound infection (n = 1). Mild and severe adhesions (81.8%), and abscess
(18.1%) formation related to translocated IUD (TIUD) were observed during
surgery. All the patients were uneventful at 1 to 5 years of follow-up. A TIUD,
by causing adhesions, complicates future laparoscopic surgery and increases the
likelihood of conversion to laparotomy. While surgery is indicated to prevent
TIUD-induced adhesive complications, it may also be the cause of both adhesions
and complications, resulting in a vicious cycle. Some asymptomatic women,
especially elderly patients with comorbidities, may not need or may be better
managed without treatment. Impact statement In this study we try to find an
answer for the question of "Should removal of a translocated intrauterine
contraceptive device (TIUD) routinely be performed even if patients are
asymptomatic?" From only the theoretical point of view there were some reports
supporting conservative management in asymptomatic patients. The other studies
addressing this issue were case reports including few patients with a short-term
follow-up. The novelties of the present study include multi-centre design,
detailed clinical and surgical information about the patients and the long period
of follow-up. Most clinicians have limited experiences in managing TIUD because
perforation is a rare event. So it can be difficult to know exactly what the
surgeon will encounter intraoperatively. We undertook this study with the aim of
providing a perspective about patients with TIUD for those faced with this
situation. This is a descriptive study reporting 15 cases of TIUDs and
management. Asymptomatic patients were managed conservatively, and symptomatic
patients were operated. There are important implications resulting from this
study that in asymptomatic patients leaving the IUD in place may be a reasonable
option, mostly as the risk of surgical intervention is quite high with a high
rate of complications with surgical management.
PMID- 28421910
TI - Multi-step treatment for acquired alexia and agraphia (part II): a dual-route
error scoring system.
AB - Dual-route neuropsychological models posit two distinct but interrelated pathways
for reading and writing: the lexical and the sublexical. Individuals with
reading/writing deficits often rely on the combined power of the integrated
system to perform print-processing tasks. The resultant errors reflect varying
degrees of lexical and sublexical accuracy in a single production; however, no
system presently exists to analyze errors robustly in both routes. The goal of
this project was to develop a system that simultaneously, quantitatively, and
qualitatively captures changes in lexical and sublexical errors following
treatment. Errors are evaluated hierarchically in both routes according to
proximity to a target. This dual-route error scoring (DRES) system was developed
using data from a novel treatment study for eight patients with acquired
alexia/agraphia; a computerised version of the system was also developed (ADRES).
Repeated-measures multivariate analyses of variance and post hoc analyses
revealed significant dual-route treatment effects. Qualitative analyses revealed
unique patterns of change across participants, reflecting the benefits of error
evaluation beyond a binary correct/incorrect judgment. Finally, categorical error
shifts were observed via group-level analysis. The results of this study indicate
that treatment-induced evolution of reading/writing can be meaningfully and
comprehensively represented by this novel scoring system.
PMID- 28421911
TI - Sleep Habits and Nighttime Texting Among Adolescents.
AB - The aim of this study was to examine sleep habits (i.e., bedtimes and rising
times) and their association with nighttime text messaging in 15- to 17-year-old
adolescents. This cross-sectional study analyzed data from a web-based survey of
adolescent students attending secondary schools in southern Sweden ( N = 278, 50%
female). Less than 8 hr of time in bed during school nights was significantly
associated with more sleep difficulties, wake time variability on school days and
weekends, daytime tiredness, and less enjoyment at school (all ps < .05). Sending
and/or receiving text messages (Short Message Service [SMS]) at night was
significantly associated with later bedtimes, shorter time in bed, daytime
tiredness during school, and irregular sleep habits ( p < .05). These findings
highlight the importance of regular, consistent sleep habits and the problems
associated with sleeping with a cell phone in the bedroom.
PMID- 28421912
TI - A Survey of School Nurse Emergency Preparedness 2014-2015.
AB - Well-prepared school nurses are more likely to handle emergencies properly. Thus,
assessing crisis management preparedness is important. In August 2014, a
questionnaire was sent to 275 nurses in a large Texas school system to collect
data about nurse and school characteristics, emergency frequency and management,
and equipment availability. Completed surveys (201, 73%) were analyzed. Fisher's
exact test was used to evaluate comparisons among nurses' confidence levels,
school characteristics, emergencies, and medical emergency response plans (MERP).
Logistic regression was used to estimate associations between characteristics and
nurses reporting less confidence. Most respondents were experienced nurses.
Shortness of breath was the most common event faced. Odds of less confidence were
significantly higher among nurses with <5 years' experience, working at
elementary schools, schools without a MERP or where it was not practiced, or
caring for <10 schoolchildren weekly. Overall, recommended emergency management
guidelines were met.
PMID- 28421913
TI - Type VI Secretion Systems of Erwinia amylovora Contribute to Bacterial
Competition, Virulence, and Exopolysaccharide Production.
AB - The type VI secretion system (T6SS) plays a major role in mediating
interbacterial competition and might contribute to virulence in plant pathogenic
bacteria. However, the role of T6SS in Erwinia amylovora remains unknown. In this
study, 33 deletion mutants within three T6SS clusters were generated in E.
amylovora strain NCPPB1665. Our results showed that all 33 mutants displayed
reduced antibacterial activities against Escherichia coli as compared with that
of the wild-type (WT) strain, indicating that Erwinia amylovora T6SS are
functional. Of the 33 mutants, 19 exhibited reduced virulence on immature pear
fruit as compared with that of the WT strain. Among them, 6, 1, and 12 genes
belonged to T6SS-1, T6SS-2, and T6SS-3 clusters, respectively. Interestingly,
these 19 mutants also produced less amylovoran or levan or both. These findings
suggest that E. amylovora T6SS play a role in bacterial competition and virulence
possibly by influencing exopolysaccharide production.
PMID- 28421914
TI - Seeing the forest but not the trees: Heterogeneity in community size effects in
Canadian ice hockey players.
AB - The community size effect (or birthplace effect) suggests that high-performance
athletes are less likely to emerge from regions with population sizes that are
very small or very large. However, previous research on elite Canadian ice hockey
players has not considered the influence of intra-national regional variation of
population distributions with respect to community size effects. Therefore, the
purpose of the current study was to test the heterogeneity of the community size
effect between Canadian National Hockey League draftees (2000-2014: n = 1505),
from 7 provincial regions within Canada (i.e., British Columbia, Alberta,
Saskatchewan, Manitoba, Ontario, Quebec and the Atlantic Provinces). The
proportion of athletes in the 9 census population categories were compared to the
national and regional general population distributions in the census categories.
Results suggest variability of community size effects between the 7 provincial
regions within Canada, with only the province of Ontario demonstrating a
community size effect congruent with effects reported in previous research. Using
regional general population distributions as the comparator to athlete
populations changed the direction, meaningfulness and magnitude of community size
effects. In conclusion, elite ice hockey player community size effects may not be
generalisable to all regions within Canada.
PMID- 28421915
TI - Use of a Modified Classic BT Shunt in a Patient With Multiple Conduit
Obstructions With Positive Lupus Anticoagulant.
AB - The use of a right ventricle-to-pulmonary artery conduit has re-emerged as a
popular alternative to a systemic artery-to-pulmonary artery shunt in the Norwood
procedure. Both proximal obstruction secondary to dynamic compression and distal
obstruction at the anastomosis site with the pulmonary arteries are well
described. In an effort to prevent complications, a technique where in the
conduit is placed through the entire full thickness, or dunked, through the RV
free wall has been described. We report a case of a patient with HLHS and
positive lupus anticoagulant who developed recurrent conduit obstructions. The
"Sano" was abandoned in favor of an autologous source of pulmonary blood flow-the
modified Blalock-Taussig shunt using the "turn down" of the carotid artery.
PMID- 28421916
TI - Mucopolysaccharidoses Causing Valvular Heart Disease: Report and Review of
Surgical Management.
AB - Mucopolysaccharidosis type I is a genetic disorder with impaired
glycosaminoglycan degradation. Cardiac pathologic involvement in this subset of
patients is predominantly valvular heart disease. Valvular heart disease seen in
these patients will most likely require surgical intervention in their lifetime.
Only a limited amount of reports are dedicated to the cardiac surgical management
of mucopolysaccharidoses. We present the case of a 32-year-old female with Hurler
Scheie syndrome who required multiple valve replacements due to progression of
valvular dysfunction and decline in the quality of life. Multidisciplinary
evaluation and discussion early are crucial for quality of life optimization in
this cohort of patients.
PMID- 28421918
TI - Number of mature applicants drops dramatically.
AB - The government is storing up problems for the future after it emerged
applications to nursing programmes from mature students have dropped by more than
one quarter, says the RCN.
PMID- 28421917
TI - The money doesn't go round.
AB - I've never felt the need to respond to an article before, but I had to comment on
the story about the NMC not increasing the L120 annual registration fee for
nurses (news, 5 April).
PMID- 28421919
TI - The power of music.
AB - At the end of the first year of my nursing degree I spent my clinical placement
in a hospice, where the majority of patients were admitted for palliative care.
PMID- 28421920
TI - Online bereavement support.
AB - How much difference can a virtual cup of tea make? A surprising amount, says
Elise Hoadley.
PMID- 28421921
TI - London trust enjoys boost in job applicants thanks to television documentary
series.
AB - A major London hospital trust that was the subject of a hit TV documentary series
has seen a surge in nurses and other staff applying to work there.
PMID- 28421922
TI - Student life - Taking a healthy approach to social networking.
AB - It can be difficult for nurses to maintain a good work-life balance, given the
commitments and pressures of their job.
PMID- 28421923
TI - Show you have the right attitude for the job.
AB - The 2013 Francis report into the Mid Staffs care scandal called for 'changes in
attitudes, culture, values and behaviour'. Since then, many NHS trusts have tried
to ensure their staff values align to those of the organisation and reflect the
NHS Constitution.
PMID- 28421925
TI - Get away from it all in the Shetlands.
AB - Fed up with the hustle and bustle of hospital life? A dream job has just come up
on the remote Scottish island of Fair Isle.
PMID- 28421926
TI - A Handbook for Student Nurses Benbow Wendy and Jordan Gill A Handbook for Student
Nurses 256pp L14.99 Lantern Publishing 9781908625373 1906052190 [Formula: see
text].
AB - Social media groups for nursing students are often inundated with excited new
students requesting pre-course reading recommendations. This book should be high
on the list for all new nursing students to have on their bookshelf.
PMID- 28421927
TI - Walking Forward, Looking Back Lantham Dinah Walking Forward, Looking Back 160pp
L8.99 Trobador Books 9781784620844 178462084X [Formula: see text].
AB - The author of Walking Forward, Looking Back is a retired district nurse and
midwife and this book is a heartwarming reflection on her life told as she
recalls past events while out walking her dog.
PMID- 28421928
TI - My Cortisol.
AB - My Cortisol is an app that helps to train parents and carers in how to give life
saving injections to children at risk of adrenal crisis.
PMID- 28421929
TI - The value of doing your best.
AB - Claire Matata is lead nurse for emergency and acute clinical research at
Northumbria Specialist Emergency Care Hospital. She completed her degree in adult
nursing at the University of Liverpool in 2010, and has worked in thoracic
surgery, community and prison nursing and as a specialist research nurse and
senior clinician in urgent care. In 2015, she spent three months in Sierra Leone
during the Ebola crisis.
PMID- 28421931
TI - Back to former Ebola zone.
AB - Pauline Cafferkey is planning to return to Sierra Leone for the first time since
falling seriously ill with the Ebola virus in 2014.
PMID- 28421930
TI - A difficult transition.
AB - More than 700,000 people in the UK are living with an eating disorder. They can
experience physical complications, poor quality of life, disrupted relationships,
emotional distress, social isolation and economic disadvantage. The risk of early
death is one of the highest among patients with psychiatric disorders.
PMID- 28421932
TI - Learning disability nurse numbers heading in the wrong direction.
AB - The UK's record on supporting people with learning disabilities is patchy to say
the least. For decades people were housed in inappropriate institutions where
abuse was rife, and attempts to improve their lives by delivering better services
in the community have come up short because they have not been afforded
sufficient priority.
PMID- 28421933
TI - RCN asks: are you prepared to strike for better pay?
AB - The RCN has opened an online poll on whether members would strike over pay. Some
270,000 RCN members are being asked for their views on NHS pay, two weeks after
governments in England, Scotland and Wales announced the latest below-inflation
pay increases.
PMID- 28421934
TI - Readers' panel - Should NHS staff be pressurised to give up their agency work?
AB - Our experts consider a hot topic of the day.
PMID- 28421935
TI - Health is your wealth - and your responsibility.
AB - What should I do? I mustn't nanny him. He is a grown man with a job. It is his
life, his health, his problem. But still.
PMID- 28421936
TI - British-led research uncovers new details on brain cancer.
AB - Scientists have found 13 new genetic errors associated with an increased risk of
developing glioma, the most common form of brain cancer.
PMID- 28421937
TI - Rules of attraction.
AB - Nottingham University Hospitals NHS Trust is the latest in a small, select band
of UK hospitals working to achieve Magnet hospital accreditation. Along with
Oxford University Hospitals and the Heart of England NHS Foundation Trust in
Birmingham, Nottingham is a key member of the new UK Magnet Alliance, which
brings together UK healthcare organisations interested in pursuing Magnet
recognition.
PMID- 28421938
TI - Agency nursing goes PAYE.
AB - Many agency nurses bill for their services through a limited or personal services
company. In the past, this has reduced the tax they need to pay, allowing some
profits to be taken as dividends. It has also allowed them to offset costs, such
as travel, against their profits.
PMID- 28421939
TI - The NMC wants to communicate in a way that works for you.
AB - Two years ago the Nursing and Midwifery Council (NMC) made a commitment, as part
of our five-year strategy, to be a leading, dynamic regulator. This means
protecting the public by being forward-looking and adapting our approach to
regulation to reflect the circumstances in which nurses and midwives work.
PMID- 28421940
TI - Not a level playing field.
AB - Your news story on the 'Nurse First' fast-track course is interesting (news
online, 31 March). Superficially, the two-year programme appears to be a good way
of recruiting talented and appropriately qualified graduates into a nursing
career.
PMID- 28421941
TI - Nurses need support, too.
AB - Like everyone, I feel for the family of Charlie Gard, the baby who the High Court
ruled last week should be allowed to die.
PMID- 28421944
TI - Awareness of heart failure unchanged in a decade.
AB - Campaigns on the risks of heart failure have failed to raise public awareness,
according to researchers.
PMID- 28421942
TI - The personal touch.
AB - The story on your Facebook page about nurses in Denmark breaking protocol to give
a dying man a glass of wine and a cigarette (11 April) reminded me of the time we
did the same thing for one of our patients on night duty.
PMID- 28421945
TI - Post-traumatic stress symptoms relieved by playing computer game.
AB - Playing the computer game Tetris can prevent post-traumatic stress symptoms,
researchers have found.
PMID- 28421947
TI - Budget cuts will hinder new nurse standards.
AB - The Council of Deans of Health has had more than a year of extensive engagement
with the Nursing and Midwifery Council's standards for future registered nurses.
PMID- 28421946
TI - 'It's a privilege to look after these children'.
AB - Moving from children's to adult services is a daunting time for any young person
and those who care for them, but for those with rare diseases it can be
particularly challenging.
PMID- 28421948
TI - Talk about fertility, even with children, says college.
AB - The RCN is encouraging nurses to talk about preserving fertility with young
people undergoing treatment that could make it difficult for them to conceive.
PMID- 28421949
TI - Vital signs.
AB - A snapshot of the state of health and social care.
PMID- 28421950
TI - Hospital visitors' experiences at the nurses' station.
AB - Aim To investigate participants' experiences of visiting hospitalised friends and
family members in adult acute medical or surgical wards in NHS hospitals in
England, to improve knowledge of hospital visiting practices and to inform future
policy-making and professional practice. Method A review of the contextual
influences and the literature identified that hospital visitors might experience
many of the characteristics of liminality, which is a state of being between two
social structures or ways of being. In 2013, a total of 17 semi-structured,
recorded and transcribed interviews were conducted with participants who had been
hospital visitors in the period 2011-2013. The transcribed interviews underwent a
thematic analysis. Liminality was then used as an analytic lens, and was central
to the theoretical framework that was constructed to further consider the
experiences of hospital visitors. Findings Participants experienced the
hospitalisation of their friend or family member and their subsequent role as
hospital visitors as a suspension of their everyday lives. Liminality was a
predominant and consistent theme of the interviews. Five main themes of
liminality were identified in relation to hospital visitors' experiences: total
obedience; loss of status; ambiguity and being betwixt and between; uncertainty;
and structure and communitas. The findings suggested that nurses consider the
area behind the nurses' station as 'back stage'; a place they can use for
downtime, socialising and computer work. In contrast, hospital visitors perceive
the nurses' station to be a continuation of the ward, where they expect
professional 'front stage behaviour' from staff. Conclusion When hospital
visitors, already discomfited in their liminal status, encounter nurses' 'back
stage behaviour' at the nurses' station, their feelings of marginalisation,
exclusion and mistrust increase. This may lead them to judge that the nurses lack
professionalism and care, which can lead them to make complaints. Increased
awareness of hospital visitors' perceptions might result in fewer complaints, and
enable more NHS resources to be directed at improving patient care.
PMID- 28421951
TI - Mindfulness.
AB - What was the nature of the CPD activity, practice-related feedback and/or event
and/or experience in your practice? The CPD article discussed mindfulness and
self-compassion, and how these concepts can improve nurses' well-being and their
ability to provide compassionate care.
PMID- 28421952
TI - Implementing spiritual care interventions.
AB - This article, the third and final in a series of three, discusses the
implementation of spiritual care interventions by nurses. It describes how nurses
can use clinical reasoning and the nursing process to implement appropriate
spiritual care for patients, and outlines the competencies necessary to identify
spiritual distress and meet the spiritual needs of patients. Spiritual care
interventions are discussed as part of a multidisciplinary team approach to the
provision of holistic care.
PMID- 28421953
TI - Multiple morbidities assessment.
AB - Essential facts Multimorbidity, when a person has two or more long-term health
conditions, is associated with a reduced quality of life, higher mortality,
polypharmacy and high treatment burden, higher rates of adverse drug events, and
much greater health service use.
PMID- 28421954
TI - Poor sleep linked to increased risk of heart attack and stroke.
AB - Insomnia is associated with an increased risk of heart attack and stroke,
according to a study in China. Researchers carried out a meta-analysis of 15
cohort studies to assess the association between insomnia symptoms and incidence
or death from cardiovascular disease and stroke.
PMID- 28421955
TI - Further evidence that taking statins can reduce risk of blood clots.
AB - More evidence has come to light that seems to suggest statins could significantly
reduce the occurrence of blood clots in certain parts of the body.
PMID- 28421956
TI - 'My midwife made childbirth a positive and enjoyable experience'.
AB - I was expecting my first baby. I was nervous and in slow labour. When I called
the maternity unit at Queen Elizabeth Hospital in Gateshead for reassurance over
the phone, midwife Anna Marley was on shift.
PMID- 28421957
TI - What the student saw: sharing placement experiences to improve practice.
AB - When nursing students go on clinical placement they see patient safety practice
in action - good and bad.
PMID- 28421958
TI - Acute limb compartment syndrome in the lower leg following trauma: assessment in
the intensive care unit.
AB - Acute limb compartment syndrome (ALCS) is a serious complication of traumatic
injury. Although ALCS can occur in any limb, it most commonly occurs following
injury to the lower leg, particularly in fractures of the tibia. Practitioners
should recognise and treat ALCS as early as possible to prevent the development
of further, potentially serious, complications. Most of the literature recommends
that patients at risk of ALCS should be carefully monitored, with a focus on pain
as the main symptom. However, patients in the intensive care unit (ICU) who are
unconscious or sedated may be unable to report pain or are unreliable in doing
so, therefore it is necessary to consider alternative assessments for ALCS. This
article provides an overview of the evidence and guidelines in relation to ALCS
in the lower leg and how to undertake an effective assessment for the condition
in patients in the ICU. This will enable practitioners to make evidence-based
clinical decisions to improve practice and patient safety.
PMID- 28421959
TI - Regulator penalises nurse who failed to start CPR.
AB - A nurse has been reprimanded by the Nursing and Midwifery Council (NMC) for
failing to begin cardiopulmonary resuscitation (CPR) on a care home resident that
he believed had already died.
PMID- 28421962
TI - Nurse's key role after Swedish attack.
AB - A nurse has spoken about being one of the first people on the scene of a terror
attack in the Swedish capital Stockholm this month.
PMID- 28421963
TI - Notice board.
AB - Courses, events, grants, and awards to progress your career.
PMID- 28421964
TI - Decline in degree places for learning disability nursing.
AB - The number of places on learning disability nursing undergraduate programmes have
either decreased or remained unchanged at 21 out of 24 universities in England in
the past two academic years, Nursing Standard can reveal.
PMID- 28421965
TI - Reducing premature mortality from non-communicable diseases.
AB - Cardiovascular disease and other non-communicable diseases, such as diabetes,
cancer and chronic respiratory disease, are a leading cause of premature death
and disability worldwide. This article emphasises the importance of prevention in
reducing death and disability from preventable non-communicable diseases,
especially for individuals with established risk factors for these diseases. It
reviews global initiatives to reduce morality rates from these diseases,
identifies opportunities for nurses and other healthcare professionals to discuss
risk factors with patients, and provides practical suggestions on how to provide
advice on healthy lifestyles and enable behaviour change.
PMID- 28421966
TI - Regulatory Forum Review*: Utility of in Vitro Secondary Pharmacology Data to
Assess Risk of Drug-induced Valvular Heart Disease in Humans: Regulatory
Considerations.
AB - Drug-induced valvular heart disease (VHD) is a serious side effect linked to long
term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B)
agonists. Safety assessment for off-target pharmacodynamic activity is a common
approach used to screen drugs for this undesired property. Such studies include
in vitro assays to determine whether the drug is a 5-HT2B agonist, a necessary
pharmacological property for development of VHD. Measures of in vitro binding
affinity (IC50, Ki) or cellular functional activity (EC50) are often compared to
maximum therapeutic free plasma drug levels ( fCmax) from which safety margins
(SMs) can be derived. However, there is no clear consensus on what constitutes an
appropriate SM under various therapeutic conditions of use. The strengths and
limitations of SM determinations and current risk assessment methodology are
reviewed and evaluated. It is concluded that the use of SMs based on Ki values,
or those relative to serotonin (5-HT), appears to be a better predictor than the
use of EC50 or EC50/human fCmax values for determining whether known 5-HT2B
agonists have resulted in VHD. It is hoped that such a discussion will improve
efforts to reduce this preventable serious drug-induced toxicity from occurring
and lead to more informed risk assessment strategies.
PMID- 28421967
TI - Lung Tumor Induction by 26-week Dermal Application of 1,2-Dichloroethane in CB6F1
Tg rasH2 Mice.
AB - Short-term alternatives to traditional 2-year carcinogenic studies in rodents are
being actively pursued. Recently, a 26-week short-term carcinogenicity study
using CB6F1-Tg rasH2@Jcl (rasH2) mice has become a worldwide standard for the
evaluation of chemical carcinogenesis. However, an acceptable short-term
carcinogenic study model for dermally applied products is still lacking. To
investigate the suitability of using the rasH2 mouse to test carcinogenic
potential, 1,2-dichloroethane (1,2-DCE) was dermally applied to rasH2 mice: 1,2
DCE is a known carcinogen that causes lung bronchiolo-alveolar adenomas and
adenocarcinomas when administered topically, orally, or by inhalation exposure;
1,2-DCE at a dose level of 126 mg/mouse in 200 MUl acetone or acetone alone
(vehicle control) was applied to the dorsal skin of 10 mice of each sex 3 times a
week for 26 weeks. As a positive control, 10 mice of each sex received a single
intraperitoneal injection of 75 mg/kg of N-methyl- N-nitrosourea. Bronchiolo
alveolar adenomas and adenocarcinomas were significantly increased in 1,2-DCE
treated rasH2 mice of both sexes, and bronchiolo-alveolar hyperplasias were
significantly increased in female mice. Overall, almost all mice of each sex
developed adenomas and/or adenocarcinomas with 100% of female rasH2 mice
developing bronchiolo-alveolar adenocarcinomas.
PMID- 28421968
TI - Chronic Toxicology Studies of Basal Insulin Peglispro in Rats and Dogs: A Novel,
PEGylated Insulin Lispro Analog with a Prolonged Duration of Action.
AB - Basal insulin peglispro (BIL) consists of insulin lispro with a 20-kDa
polyethylene glycol (PEG) moiety covalently attached to lysine B28. Because
chronic parenteral administration of PEGylated proteins to animals has sometimes
resulted in PEG vacuolation of tissue macrophages, renal tubular cells, and
choroid plexus ependymal cells, we investigated whether chronic subcutaneous (sc)
injection of BIL in rats (52 weeks) and dogs (39 weeks) was associated with
systemic toxicities or other changes, including vacuolation of tissue
macrophages, renal tubular cells, and ependymal cells. Rats and dogs received
daily sc injections of BIL (rats: 0.17, 0.45, or 1.15 mg/kg/d and dogs: 0.025,
0.10, or 0.20 mg/kg/d) and the reference compound, HUMULIN N(r) (neutral
protamine Hagedorn [NPH] human insulin; rats: 0.15 mg/kg/d and dogs: 0.02-0.03
mg/kg/d). Animals were evaluated for standard end points including mortality,
clinical signs, body weights, toxicokinetics, glucodynamics, clinical pathology,
and morphological pathology. Nonadverse injection site lipohypertrophy occurred
for all BIL and NPH doses but more frequently with BIL. No BIL-related
hyperplasia or neoplasia was observed. There was no vacuolation of tissue
macrophages, renal tubular cells, or ependymal cells attributable to PEG. These
studies demonstrate BIL is not associated with tissue vacuolation attributable to
PEG at 4- to 6-fold multiple of the median clinical exposure in patients with
diabetes.
PMID- 28421969
TI - Dystrophic Mineralization of Costal Cartilage in Hartley Guinea Pigs.
AB - Hartley guinea pigs are widely used animal models of disease, particularly in
studies of osteoarthritis. The purpose of this study was to investigate lesions
in the costal cartilage from 16 male, 5- to 6-month-old Hartley guinea pigs.
Routine histological sections from the costal cartilage and costochondral
junction (longitudinal and cross sections) and sternum (for evaluation of bone
marrow) were examined. All 16 (100%) animals had histological lesions involving
the costal cartilage that included matrix degeneration and mineralization,
reduced cellularity, and evidence of chondrocyte necrosis. Of the 16, 4 (25%) of
the lesions contained blood vessels and 3 (19%) contained central osseous
metaplasia. The cartilage lesions were accompanied by degeneration (sometimes
with regeneration and/or fibrosis) in adjacent skeletal muscle in 15 of the 16
(94%) animals. The lesions in the costal cartilage were interpreted as dystrophic
mineralization of unknown cause and appear to be incidental findings, although
they bear some resemblance to lesions occurring in Tietze's disease in humans.
The significance of the lesions in skeletal muscle is unclear. Histological
lesions of cartilage matrix degeneration and mineralization in these sites have
not, to our knowledge, been reported previously.
PMID- 28421970
TI - Management of Fractured Inferior Vena Cava Filters: Outcomes by Fragment
Location.
AB - Purpose To inform the management of fractured inferior vena cava filters on the
basis of results from a tertiary referral center specializing in complex filter
retrieval. Materials and Methods This study had institutional review board
approval and was HIPAA compliant. Retrospective analysis of all patients with
fractured filters and/or filter fragments evaluated for removal in a complex
filter removal program was performed. Removal was attempted when fragments were
intravascular or immediately extravascular by using primarily endobronchial
forceps for caval fragments and snares for cardiac and pulmonary fragments. Data
collected included success rate and complications of filter and fragment removal,
symptoms relating to the filter or fragment, techniques used for removal, and
follow-up of retained fragments. Results Sixty-five patients (12 men, 53 women)
of a total of 222 patients referred for complex retrieval had fractured filters.
Of these patients, two had undergone filter removal elsewhere and had retained
fragments. All 63 filters were removed successfully with forceps (n = 61), a cone
(n = 1), or a snare (n = 1). There were 116 separate filter fragments; removal
was attempted for 78 fragments. Removal was successful for 63 (81%) of 78
fragments and varied by location. All extravascular fragments except one were
retained. In all, 63 (54%) of 116 fragments were removed percutaneously,
rendering 34 (54%) of 63 patients fragment free. Five minor (7.7% [five of 65])
and four major (6.2% [four of 65]) complications occurred. Conclusion
Intravascular filter fragments can be removed safely with success rates that vary
according to location. Because extravascular fragments are not readily accessible
for removal, many patients are not rendered fragment free. (c) RSNA, 2017 Online
supplemental material is available for this article.
PMID- 28421971
TI - [Posttraumatic appendicitis].
AB - BACKGROUND: Posttraumatic appendicitis is an appendicitis that develops as a
consequence of abdominal trauma. Trauma is a relatively rare cause of
appendicitis which is nowadays rarely mentioned in surgical textbooks. CASE
DESCRIPTION: We describe the case of a 12-year-old girl who presented to the
emergency department six days after abdominal trauma caused by a fall from an
electrical bicycle, complaining of fever and abdominal pain. Her symptoms were
caused by a perforated appendicitis. Her recovery after appendectomy was
complicated by abscess formation and subsequent drainage, and the need for
parenteral nutrition CONCLUSION: Abdominal pain and fever several days after an
abdominal trauma may be a sign of posttraumatic appendicitis. The clinical signs
and diagnostic work-up do not differ significantly from that of appendicitis with
a different aetiology. Trauma is not a well-known cause of appendicitis, and this
can cause delay in diagnosis and treatment.
PMID- 28421972
TI - [A tumour mistaken for a scar].
AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare type of cutaneous
soft tissue sarcoma. The tumour metastasises rarely, but the percentage of
recurrences is high and the tumour can be locally very aggressive. CASE
DESCRIPTION: A 50-year-old man was referred to our clinic for a long existing
scar on his back, which had become painful in the last few weeks. In the hospital
we decided to take a biopsy. Based on the histopathological investigation, the
diagnosis DFSP was made. The patient was referred to a tertiary centre
specialising in rare skin malignancies. CONCLUSION: DFSP is clinically
heterogeneous with the consequence that several differential diagnoses can be
made. Histopathological examination is the gold standard diagnostic approach when
there is a possible suspicion of DFSP. Because of the aggressiveness and the high
recurrence rate it is very important to make a timely diagnosis, to allow
appropriate treatment - preferably radical excision - to take place.
PMID- 28421973
TI - [Bitten by an exotic venomous snake].
AB - BACKGROUND: Patients who have been bitten by an exotic venomous snake are at risk
of severe morbidity and a fatal outcome following an incorrect risk-assessment.
Treatment with an antivenom can be necessary and can turn out to be lifesaving.
In the Netherlands there are only a few cases of bites from exotic venomous
snakes each year. CASE DESCRIPTION: A 28-year-old man presented at the emergency
department (ED) after having been bitten by a monocled cobra (Naja kaouthia).
Here he developed severe neurotoxicity with respiratory insufficiency requiring
intubation and mechanical ventilation. The patient was successfully treated with
an antivenom. CONCLUSION: An exotic snakebite victim is always a medical
emergency. With early presentation at the ED, proper assessment, treatment and
the availability of antivenom from the National Serum Depot, this will not
necessarily cause insurmountable problems.
PMID- 28421974
TI - [Epigastric pain caused by a gastric wall abscess].
AB - BACKGROUND: Gastric wall abscesses are rare, but mortality rates from this type
of gastritis are high. A foreign body or mucosal damage is often the cause of the
abscess. Most patients have nonspecific symptoms, including general malaise and
abdominal pain, sometimes accompanied by fever and weight loss. CASE DESCRIPTION:
After various tests a 45-year-old man with epigastric pain was shown to have a
gastric wall abscess. After endoscopic drainage of the abscess, followed by
intravenous antibiotics, he made a complete recovery. CONCLUSION: Gastric wall
abscesses are rare, but should be included in the differential diagnosis in
patients with epigastric pain, because of their high mortality rate. Endoscopic
ultrasonography is the preferred diagnostic method. Endoscopic ultrasound-guided
drainage, with or without placement of a drain, followed by intravenous
antibiotics is the treatment of choice.
PMID- 28421975
TI - [Analysis of variation in the surgical treatment of distal radius fracture].
AB - OBJECTIVE: The optimum treatment of patients with distal radius fracture has not
been entirely clarified resulting in possible major variations between hospitals
in the number of patients undergoing surgical treatment. The objective of this
study was to examine the variation in surgical treatment rates of patients with
distal radius fractures across Dutch hospitals. DESIGN: Retrospective study.
METHOD: Aggregated data for all patients with a distal radius fracture were
obtained for 2012 and 2013 on the basis of reimbursement codes. The surgical rate
across hospitals was corrected for several variables using linear regression
analysis. RESULTS: We analysed a total of 95,754 reimbursements. The operative
rate ranged from 0% to 23%, with a mean of 9.6%. Hospital type, the percentage of
females, the percentage of patients over 65, the mean age, average socioeconomic
status, and the total number of patients treated explained only 2.6% of the
observed differences in operative rate between hospitals in 2012 and 11.6% in
2013. CONCLUSION: Our results suggest that non-scientific factors, such as
surgeon's age, background, and local culture, influence therapeutic decisions in
patients with distal radius fractures.
PMID- 28421976
TI - [Measles after MMR-vaccination].
AB - BACKGROUND: The Dutch national vaccination program provides vaccination for
mumps, measles and rubella (MMR vaccine) for all children. After vaccination with
live attenuated viruses, the virus replicates on a limited scale. Replication may
lead to mild symptoms occurring 5-14 days after MMR-vaccination, including fever,
conjunctivitis and rash. Symptoms are comparable to those of a wildtype measles
infection. CASE DESCRIPTION: A 14-month-old boy was admitted to the hospital with
an impressive rash 13 days after MMR-vaccination. Diagnostic tests were positive
for measles. This test result caused the mother to doubt further vaccination.
CONCLUSION: Within 14 days after MMR-vaccination, a child can present with
symptoms very similar to a wildtype measles virus infection. The low incidence of
wildtype measles infection strongly suggests that these symptoms will likely be a
reaction to vaccination. Elaborate diagnostic procedures may cause the parents a
lot of stress and therefore offering reassurance to parents may be more
appropriate.
PMID- 28421977
TI - [A woman with pink urine and a pink skin].
AB - A 48-year-old woman with fire-related inhalation injury had pink urine and a pink
skin. This was caused by hydroxocobalamin, which was used to treat cyanide
poisoning.
PMID- 28421978
TI - Improving Patient Safety Through Antibiotic Stewardship: The Veterans Health
Administration Leads the Way, Again.
PMID- 28421979
TI - Applying the Horizontal and Vertical Paradigm to Antimicrobial Stewardship.
PMID- 28421981
TI - Validation of MAX Aqueous Extraction on Veratox(r) for Total Aflatoxin ELISA Test
Kit.
AB - Neogen Corp. (Lansing, MI) has developed a common aqueous extraction method for
the detection of mycotoxins in the ELISA or lateral flow format. The Veratox(r)
for Total Aflatoxin ELISA extraction method uses a MAX 2 extraction packet and
water in replacement of traditionally used organic solvents. Veratox for Total
Aflatoxin has a detection range of 5-50 ppb neat or up to 300 ppb with dilution.
The kit development focused on superior cross-reactivity, ability to accurately
detect naturally contaminated samples, and utilization of an aqueous extraction
method. In two separate validation studies, the Veratox for Total Aflatoxin test
kit resulted in average yields of 91-114% in naturally contaminated mycotoxin
reference material corn. The cross-reactivity profiles for aflatoxins B1, B2, G1,
and G2 were 100, 113, 103, and 93%, respectively. This kit is approved by the
Grain Inspection, Packers, and Stockyards Administration.
PMID- 28421980
TI - Guidelines for the recognition and management of mixed depression.
AB - A significant minority of people presenting with a major depressive episode (MDE)
experience co-occurring subsyndromal hypo/manic symptoms. As this presentation
may have important prognostic and treatment implications, the DSM-5 codified a
new nosological entity, the "mixed features specifier," referring to individuals
meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or
to individuals with syndromal mania and subthreshold depressive symptoms. The
mixed features specifier adds to a growing list of monikers that have been put
forward to describe phenotypes characterized by the admixture of depressive and
hypomanic symptoms (e.g., mixed depression, depression with mixed features, or
depressive mixed states [DMX]). Current treatment guidelines, regulatory
approvals, as well the current evidentiary base provide insufficient decision
support to practitioners who provide care to individuals presenting with an MDE
with mixed features. In addition, all existing psychotropic agents evaluated in
mixed patients have largely been confined to patient populations meeting the DSM
IV definition of "mixed states" wherein the co-occurrence of threshold-level
mania and threshold-level MDE was required. Toward the aim of assisting
clinicians providing care to adults with MDE and mixed features, we have
assembled a panel of experts on mood disorders to develop these guidelines on the
recognition and treatment of mixed depression, based on the few studies that have
focused specifically on DMX as well as decades of cumulated clinical experience.
PMID- 28421982
TI - Simultaneous Determination of Volatile Organic Compounds in Commercial Alcoholic
Beverages by Gas Chromatography with Flame Ionization Detection.
AB - A simple and fast method was developed for the determination of volatile organic
compounds in alcoholic beverages. Eleven volatile organic compounds
(acetaldehyde, methanol, 2-propanol, tert-butanol, 1-propanol, ethyl acetate, 2
butanol, isobutanol, 1-butanol, 3-methyl-1butanol, and 2-methyl-1-butanol) in
alcoholic beverages were analyzed with a simple direct-injection method using GC
with flame ionization detection. These compounds should be monitored in the QC of
production processes because they are detrimental to human health. The method was
validated with four types of alcoholic beverages (beers, fruit wines, rice wines,
and spirits) to confirm the versatility of the method. Linearity showed r2 values
from 0.9986 to 0.9995, with LODs ranging from 0.010 to 1.000 mg/L. Precision and
accuracy showed acceptable results, proving the effectiveness of the method. The
developed method was applied to 40 commercial samples representing the four types
of alcoholic beverages, and principal component analysis was performed to
determine profiles of the volatile organic compounds, depending on the type of
alcoholic beverage.
PMID- 28421983
TI - Comparative Study Between Multivariate and Univariate Analysis of Two
Antidiabetic Combinations.
AB - New multivariate and univariate methods were developed for the analysis of two
novel gliptin combinations by manipulating the zero-order and ratio spectra of
empagliflozin and linagliptin in combination, with application on Glyxambi(r)
tablets, and of alogliptin and pioglitazone in combination, with application on
Oseni(r) tablets. Linearity ranges for chemometric approaches using principal
component regression and partial least-squares were found to be 2-10, 2.5-12.5, 5
15, and 5-25 MUg/mL for empagliflozin, linagliptin, alogliptin, and pioglitazone,
respectively, whereas the respective linearity ranges for the spectrophotometric
approaches were found to be 5-15, 2-12, 5-15, and 5-15 MUg/mL. The proposed
spectrophotometric methods included ratio subtraction coupled with extended ratio
subtraction, spectrum subtraction coupled with constant multiplication, and mean
centering. Acceptable LOD and LOQ values were obtained by all methods.
Statistical analysis showed no significant difference between multivariate and
univariate methods in comparison with the reference methods. The optimized
methods provide fast and economic determination of the recently approved
antidiabetic combinations without the complex instrumentation or time-consuming
mobile phase preparations that were used in the chromatographic techniques
reported in the literature.
PMID- 28421984
TI - Stability-Indicating UPLC Method for the Estimation of Nadifloxacin, Terbinafine
Hydrochloride, Mometasone Furoate, Methyl Paraben, and Propyl Paraben in Topical
Pharmaceutical Dosage Form.
AB - A novel and simple ultra-performance LC method was developed for the estimation
of nadifloxacin (NAD), terbinafine hydrochloride (TBH), mometasone furoate (MMF),
methyl paraben (MP), and propyl paraben (PP) in a topical pharmaceutical dosage
formulation. The analysis was carried out on a Waters Acquity UPLC ethylene
bridged hybrid C18 column (50 * 2.1 mm, 1.7 MUm) with a flow rate of 0.4 mL/min
in gradient mode at a wavelength of 255 nm. Elution of all components was
achieved within 9 min. The retention times of MP, NAD, PP, TBH, and MMF were
observed at 1.5, 2.6, 3.4, 6.0, and 6.9 min, respectively. The proposed method
was validated per current International Conference on Harmonization guidelines
for specificity, precision, linearity, accuracy, range, LOD, LOQ, robustness,
filter paper interference, and solution stability parameters. A complete method
study was performed to determine the stability-indicating nature of the developed
method.
PMID- 28421985
TI - Design of a Sensitive and Selective Electrochemical Aptasensor for the
Determination of the Complementary cDNA of miRNA-145 Based on the Intercalation
and Electrochemical Reduction of Doxorubicin.
AB - The aim of this research was the determination of a microRNA (miRNA) using a DNA
electrochemical aptasensor. In this biosensor, the complementary complementary
DNA (cDNA) of miRNA-145 (a sense RNA transcript) was the target strand and the
cDNA of miRNA-145 was the probe strand. Both cDNAs can be the product of the
reverse transcriptase-polymerase chain reaction of miRNA. The proposed
aptasensor's function was based on the hybridization of target strands with
probes immobilized on the surface of a working electrode and the subsequent
intercalation of doxorubicin (DOX) molecules functioning as the electroactive
indicators of any double strands that formed. Electrochemical transduction was
performed by measuring the cathodic current resulting from the electrochemical
reduction of the intercalated molecules at the electrode surface. In the
experiment, because many DOX molecules accumulated on each target strand on the
electrode surface, amplification was inherently easy, without a need for
enzymatic or complicated amplification strategies. The proposed aptasensor also
had the excellent ability to regenerate as a result of the melting of the DNA
duplex. Moreover, the use of DNA probe strands obviated the challenges of working
with an RNA probe, such as sensitivity to RNase enzyme. In addition to the linear
relationship between the electrochemical signal and the concentration of the
target strands that ranged from 2.0 to 80.0 nM with an LOD of 0.27 nM, the
proposed biosensor was clearly capable of distinguishing between complementary
(target strand) and noncomplementary sequences. The presented biosensor was
successfully applied for the quantification of DNA strands corresponding to miRNA
145 in human serum samples.
PMID- 28421986
TI - All-Solid-State, PVC Membrane, and Carbon Paste Ion-Selective Electrodes for
Determination of Donepezil Hydrochloride in Pharmaceutical Formulation.
AB - All-solid-state, polyvinyl chloride (PVC) membrane, and carbon paste
potentiometric ion-selective electrodes (ISEs) were proposed for the
determination of donepezil hydrochloride (DON) in the drug substance and a
pharmaceutical formulation. The potentiometric response toward DON was based on
the existence of donepezil-tetraphenyl borate (DON-TPB) in a PVC membrane or a
carbon paste in the presence of dioctylphthalate. In contrast, the solid-state
electrode was prepared by direct incorporation of DON-TPB into a commercial nail
varnish without external additives. The electrodes exhibited Nernstian slopes of
55.0, 57.0, and 53.0 mV/decade over the concentration ranges of 1 * 10-5 to 1 *
10-3, 1 * 10-4 to 10-2, and 1 * 10-4 to 5 * 10-3 for the solid-state, PVC
membrane, and carbon paste electrodes, respectively. The response of the
electrodes is independent of pH in the range of 2-<=8. The electrodes showed good
selectivity for DON with respect to a number of inorganic cations and amino
acids. The electrodes were used for the determination of DON in pure solution and
in pharmaceutical tablets with high accuracy (+/-2%) and precision (RSD <=2%).
The solid-state electrode is simple, economical, and rapid when compared to the
PVC membrane and carbon paste electrodes.
PMID- 28421987
TI - A New Dispersive Liquid-Liquid Microextraction Method for Preconcentration and
Determination of Aluminum, Iron, Copper, and Lead in Real Water Samples by HPLC.
AB - In this study, dispersive liquid-liquid microextraction coupled with HPLC with
variable-wavelength detection was applied for the simultaneous determination of
Al, Fe, Cu, and Pb in various water samples at trace levels. In the proposed
method, all the system parameters in both the extraction and
separation/determination steps, such as extraction and disperser solvent type and
their volumes, complexing reagent concentration, salt addition, extraction and
centrifugation times, and pH, were optimized to get not only high extraction
efficiency but also lower LODs for the analytes. Hematoxylin was used as a
complexing reagent, and carbon tetrachloride and methanol were chosen as the
extraction and disperser solvents, respectively. Metal complexes were separated
with a reversed-phase C18 column by isocratic elution, with methanol
tetrahydrofuran-water (20 + 12 + 68, v/v/v) as the mobile phase at a flow rate of
1.0 mL/min and detection at 575 nm. The accuracy of the method was checked by a
Standard Reference Material of water (SRM 1643e), and the recovery values for the
analytes were found in the range of 95.6-101.3%. Under the optimum conditions,
the developed method was applied to tap water, bottled mineral water, lake water,
and seawater for the accurate and sensitive determination of the analytes of
interest.
PMID- 28421988
TI - Composite Magnetic Nanoparticles (CuFe2O4) as a New Microsorbent for Extraction
of Rhodamine B from Water Samples.
AB - In this work, novel composite magnetic nanoparticles (CuFe2O4) were synthesized
based on sol-gel combustion in the laboratory. Next, a simple production method
was optimized for the preparation of the copper nanoferrites (CuFe2O4), which are
stable in water, magnetically active, and have a high specific area used as
sorbent material for organic dye extraction in water solution. CuFe2O4
nanopowders were characterized by field-emission scanning electron microscopy
(SEM), FTIR spectroscopy, and energy dispersive X-ray spectroscopy. The size
range of the nanoparticles obtained in such conditions was estimated by SEM
images to be 35-45 nm. The parameters influencing the extraction of CuFe2O4
nanoparticles, such as desorption solvent, amount of sorbent, desorption time,
sample pH, ionic strength, and extraction time, were investigated and optimized.
Under the optimum conditions, a linear calibration curve in the range of 0.75
5.00 MUg/L with R2 = 0.9996 was obtained. The LOQ (10Sb) and LOD (3Sb) of the
method were 0.75 and 0.25 MUg/L (n = 3), respectively. The RSD for a water sample
spiked with 1 MUg/L rhodamine B was 3% (n = 5). The method was applied for the
determination of rhodamine B in tap water, dishwashing foam, dishwashing liquid,
and shampoo samples. The relative recovery percentages for these samples were in
the range of 95-99%.
PMID- 28421989
TI - Application of an HPLC Method for Selective Determination of Phenazopyridine
Hydrochloride: Theoretical and Practical Investigations.
AB - HPLC method was developed for the selective determination of phenazopyridine
hydrochloride (PAP) in the presence of its computationally selected metabolite.
Density functional theory was applied as a computational model to study the
energy of PAP metabolites, and the results revealed that 2,3,6-triaminopyridine
(TAP) is the most stable metabolite. Good resolution and separation of PAP from
TAP was achieved using a reversed-phase BDS Hypersil C18 column with a mobile
phase consisting of acetonitrile-water (75 + 25, v/v) at flow rate of 1 mL/min
and with UV detection at 280 nm. The linear regression analysis data for the
calibration plot of PAP showed a good linear relationship over the concentration
range of 5-45 MUg/mL, with an LOD of 0.773 MUg/mL. Moreover, a theoretical
investigation of the relationship between the stationary phase and the studied
molecules was performed to confirm the experimental results. The proposed method
was successfully applied for the selective determination of PAP in pharmaceutical
formulation. In addition, the obtained results were statistically compared to a
reported method, with no significant differences found between the investigated
method and the reported one with respect to accuracy and precision.
PMID- 28421990
TI - Elevated levels of soluble CD40 ligand are associated with antiphospholipid
antibodies in patients with systemic lupus erythematosus.
AB - OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of
atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were
reported in SLE patients. However, the clinical implication of sCD40L in SLE
remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients
and 37 healthy controls and investigated its association with clinical
manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE
patients were significantly elevated compared with healthy controls (p=0.013) and
positively correlated with levels of soluble P-selectin (gamma=0.336, p<0.001).
SLE patients who experienced arterial thrombosis had a higher level of sCD40L
than those who did not (p=0.029). Plasma sCD40L levels were positively correlated
with the titers of anti-cardiolipin and anti-beta2 glycoprotein I antibodies
(gamma=0.338, p<0.001 and gamma=0.364, p<0.001, respectively). Its levels were
also significantly higher in patients with clinical antiphospholipid syndrome
(APS) than in non-APS patients, irrespective of antiphospholipid antibody (aPL)
positivity. Of those with arterial thrombosis, sCD40L levels were significantly
elevated in patients with positive aPL, compared to those with negative aPL
(p=0.011). Multiple regression analysis revealed that the presence of
hypertension and positive aPL were independently associated with the occurrence
of arterial thrombosis in SLE patients. A parallel analysis showed that sCD40L
was also an independent variable for arterial thrombosis; however, this
association disappeared when aPL, a strong variable, was included in the model
because of collinearity between aPL and sCD40L. CONCLUSIONS: Plasma sCD40L levels
were elevated in SLE patients who had positive aPL and experienced arterial
thrombosis, suggesting that enhanced release of sCD40L through platelet
activation presumably by aPL could contribute to the development of
atherothrombotic disease.
PMID- 28421991
TI - Patterns in use and costs of conventional and biologic disease-modifying anti
rheumatic drugs in Australia.
AB - OBJECTIVES: The aim of this study was to characterise the use and costs of
subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and
biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits
schemes. METHODS: Dispensing and expenditure data on conventional and biologic
DMARDs were extracted from Medicare Australia and temporal trends were analysed.
Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000
population per day (DDD/1,000 population/day). RESULTS: Conventional and biologic
DMARD use increased 74% over the study period (4.86 to 8.46 DDD/1,000
population/day; average annual increase 6.7%). Conventional DMARDs accounted for
the vast majority of total use and increased 55% (4.81 to 7.43 DDD/1,000
population/day), while biologic DMARD use increased 1,784% (0.055 to 1.030
DDD/1,000 population/day). The most frequently used conventional DMARD was
methotrexate (56% total conventional DMARD use) and use increased 95%.
Hydroxychloroquine and leflunomide use increased marginally while sulfasalazine
use declined 4.2%. Etanercept was the most commonly used biologic DMARD in 2004
and adalimumab in 2014. Conventional DMARD expenditure decreased 4.2% to AUD$33.3
million but biologic DMARD expenditure increased 2,089% to AUD$585.4 million.
CONCLUSIONS: The use of conventional and biologic DMARDs increased substantially
over a decade in Australia. Patterns of use of conventional DMARDs have changed,
and costs have decreased. In contrast a significant escalation in both the use
and cost of biologic DMARDs has occurred. Further research is required to address
cost-effectiveness, regulation and quality use of these medicines in clinical
practice.
PMID- 28421992
TI - Reply to comment on: Clinical efficacy of oral alendronate in ankylosing
spondylitis: a randomised placebo-controlled trial.
PMID- 28421994
TI - Reply to: Behcet's disease: an MHC-I-opathy?
PMID- 28421993
TI - Increased expression of interferon-lambda in minor salivary glands of patients
with primary Sjogren's syndrome and its synergic effect with interferon-alpha on
salivary gland epithelial cells.
AB - OBJECTIVES: To investigate the expressions of interferon (IFN)-lambdas and their
receptor, IL28RA, in minor salivary glands (MSG) of pSS patients and their
effects on the salivary gland cells. METHODS: The expressions of IFN-lambdas and
IL28RA were evaluated in MSG by immunohistochemistry in 15 patients with pSS and
in 5 patients with non-SS sicca. Poly(I:C)-induced IL-28A and IL-29 expressions
were determined in immortalized human salivary gland acinar (NS-SV-AC) and ductal
(NS-SV-DC) cell lines. We assessed the effect of IFN-lambdas on the expressions
of typical interferon-inducible genes, B-cell activating factor (BAFF) and
CXCL10, and the synergistic effect of IL-29 and type I or II IFN on their
expressions. The serum IL-29 levels were measured in 44 patients with pSS and 22
healthy controls. RESULTS: IFN-lambdas expression was significantly higher in MSG
from pSS than from non-SS sicca controls. Poly(I:C) treatment led to the
induction of IL-28A and IL-29 in the salivary gland cell lines. In the NS-SV-DC
cells, IFN-lambda significantly increased the levels of BAFF and CXCL10 in a time
and dose-dependent manner. Moreover, there was a synergistic effect between IL-29
and IFN-alpha in the induction of BAFF and CXCL10 expressions by prolonged STAT1
phosphorylation. However, the serum IL-29 levels were not significantly higher in
pSS patients than in healthy controls. CONCLUSIONS: Our results suggest the
possibility for IFN-lambda to play a role by participating local inflammation in
the salivary glands of pSS through direct and indirect regulations of the
expressions of BAFF and CXCL10 in salivary gland epithelium.
PMID- 28421995
TI - Endothelial dysfunction is independent of inflammation and altered CCR7 T cell
expression in patients with ankylosing spondylitis.
AB - OBJECTIVES: The accumulation of CCR7 (chemokine receptor 7) positive cells in the
vessel wall may be involved in endothelial dysfunction and subsequent accelerated
atherogenesis. CCR7 plays a crucial role in T cell and monocyte migration/homing
and in priming of naive T lymphocytes in non-lymphoid tissues in chronic
inflammatory diseases. Our objective was to investigate the endothelial function
and inflammation-driven expression of CCR7 on T lymphocytes in patients with
ankylosing spondylitis (AS). METHODS: We performed flow cytometry to assess the
distribution of peripheral blood T cell subpopulations in the context of serum
inflammatory markers (TNF-alpha, IL-6, sICAM-1) and asymmetric dimethylarginine
(ADMA) in 38 patients with AS with active disease, and in 20 healthy controls.
RESULTS: Patients with AS demonstrated higher ADMA (0.74+/-0.2 MUmol/l vs. 0.64+/
0.15 MUmol/l; p=0.03), as well as elevated inflammatory markers (TNFalpha, IL-6,
sICAM-1) and increased proportions of circulating CCR7-positive lymphocytes
largely attributable to elevated CD8+ naive T cells (47.1+/-17 vs. 34.3+/-13.1%;
p=0.005). However, ADMA did not correlate with either CCR7-positive lymphocytes
or inflammatory markers. CONCLUSIONS: We found an increased percentage of
peripheral CCR7 T cells accompanied by endothelial dysfunction in patients with
AS. The lack of direct associations between ADMA and inflammation may suggest the
presence of other pathogenic mechanisms contributing to accelerated atherogenesis
and increased cardiovascular risk in AS.
PMID- 28421996
TI - Obesity does not diminish the efficacy of IL-6 signalling blockade in mice with
collagen-induced arthritis.
AB - OBJECTIVES: Obese rheumatoid arthritis patients often have higher disease
activity and a poorer response to treatment than do non-obese patients. The
present study aims to clarify the influence of obesity on the action of IL-6 and
to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity.
METHODS: Mice were fed a high-fat diet for 5 weeks, and the influence of this
diet on macrophages and type II collagen-induced arthritis was investigated.
RESULTS: The mice fed the high-fat diet showed greater expression of macrophage
marker F4/80, not only in subcutaneous fat but also in knee synovium and the
calcaneal region, than did the mice fed a normal diet. Furthermore, macrophages
isolated from mice on the high-fat diet tended to show higher expression of
cyclooxygenase-2 following IL-6 stimulation than did macrophages from mice fed
the normal diet. Moreover, mice fed the normal or high-fat diet were immunised
with type II collagen, and were treated with anti-mouse IL-6 receptor antibody
(MR16-1). The anti-arthritis effect of MR16-1 was not reduced in mice fed the
high-fat diet compared to mice fed the normal diet (inhibition ratio: 87% vs.
62%). Furthermore, at the peak of arthritis, cyclooxygenase-2 expression in the
calcaneal region of mice fed the high-fat diet was higher than that in the mice
fed the normal diet. CONCLUSIONS: These results suggested that a high-fat diet
induces inflammatory changes in the synovium. We demonstrated that IL-6
signalling blockade by an anti-IL-6 receptor antibody can be effective in
treating arthritis, even with obesity.
PMID- 28421997
TI - Laser microdissection coupled with RNA-seq reveal cell-type and disease-specific
markers in the salivary gland of Sjogren's syndrome patients.
AB - OBJECTIVES: Little is known about the molecular details regarding the
contribution of different cell types of the salivary gland to the altered gene
expression profile seen in Sjogren's syndrome (SS). METHODS: Using laser
microdissection, tissue samples enriched in acini, ducts and inflammatory foci in
subjects with and without SS were isolated for RNA-seq analysis. Gene expression
profiles were analysed and selected enriched genes were further examined using
real time PCR and by immunofluorescence. RESULTS: RNA-seq analysis of salivary
biopsies from subjects with and without SS revealed marked differences in gene
expression occurring in the ductal and infiltrating cells compared to acinar
cells. Up-regulated genes in the SS ductal cells included C4A complement and the
SLC26A9 ion channel. The inflammatory infiltrate showed the most dramatic
differences in gene expression and contained up-regulated genes associated with T
cells, natural killer, dendritic and basophils/mast cells. qPCR with total
salivary gland mRNA confirmed the differential mRNA expression of several genes
(MMP9, FOL1HB, CCL21, CCR7), thereby validating the approach. Additional
immunofluorescence studies demonstrated high expression and co-localisation of
CCL21 chemokine and CCR7 chemokine receptor within the SS infiltrates.
CONCLUSIONS: Major gene expression changes in the salivary gland of SS were
detected in the ductal and inflammatory cells and not in the acinar cells. Two
chemokines involved in immune cell trafficking to secondary lymphoid tissue, CCR7
and CCL21, showed markedly increased expression and may contribute to the
recruitment of diverse immune cells to the salivary glands, causing inflammation
and loss of secretory function.
PMID- 28421998
TI - Comment on: clinical efficacy of oral alendronate in ankylosing spondylitis: a
randomised placebo-controlled trial.
PMID- 28421999
TI - Use and withdrawal of immunosuppressors in primary Sjogren's syndrome.
AB - OBJECTIVES: To assess the use and causes of withdrawal of glucocorticoids and
immunosuppressors among patients with primary Sjogren's syndrome (pSS) in the
clinical setting. METHODS: We retrospectively reviewed the medical records of 155
pSS patients and registered demographics, glandular/extraglandular features,
serological data, cumulative ESSDAI and SSDDI. A single rheumatologist attributed
the indication and cause of withdrawal of glucocorticoids and immunosuppressors.
RESULTS: 92.2% of the patients were female, mean age 57.4+/-14.7 years and median
follow-up 11 years. One hundred and four (67%) patients received glucocorticoids
and/or immunosuppressors: 3.8% only glucocorticoids, 43.9% only immunosuppressors
and 56.5% their combination. The most used drugs were antimalarials (46.4%),
prednisone (36.7%), azathioprine (AZA) (23.8%) and methotrexate (MTX) (18%). At
the multivariate analysis, the presence of non-erosive arthritis OR 5.02 (95% CI
1.74-14.47, p=0.003) and the median cumulative ESSDAI score OR 1.10 (95% CI 1.03
1.17, p=0.002) were associated with the use of these drugs. The causes of
withdrawal were: 39% improvement, 35.2% patient's own decision, 18.1% toxicity
and 11% lack of efficacy. We found toxicity in 14.2% MTX users, 9.7% for AZA,
9.7% for antimalarials and 7.6% for cyclophosphamide. CONCLUSIONS: More than half
the patients received glucocorticoids and/or immunosuppressors and a not
negligible number decided on their own to suspend them, alerting physicians of
secondary adverse events and tolerability.
PMID- 28422000
TI - Fibromyalgia in 300 adult index patients with primary immunodeficiency.
AB - OBJECTIVES: We sought to determine the prevalence and clinical and laboratory
associations of fibromyalgia in adults with primary immunodeficiency
(immunoglobulin (Ig) G subclass deficiency (IgGSD) and common variable
immunodeficiency (CVID). METHODS: We performed a retrospective analysis of these
observations in 300 non-Hispanic white adult index patients with recurrent/severe
respiratory tract infections and IgGSD or CVID: age; sex; IgGSD; fibromyalgia;
chronic fatigue; autoimmune conditions (ACs); interstitial cystitis (IC);
diabetes; body mass index; serum Ig isotypes; blood lymphocytes and subsets; and
human leukocyte antigen (HLA)-A and -B types and haplotypes. We performed
univariate comparisons, logistic multivariable regressions, and an analysis of
covariance. RESULTS: Mean age was 49 +/- 12 (standard deviation) y. There were
246 women (82.0%). IgGSD was diagnosed in 276 patients (92.0%). Fifty-six
patients had fibromyalgia (18.7%; female:male 13:1). Other characteristics
included: chronic fatigue, 63.0%; aggregate ACs, 35.3%; Sjogren's syndrome, 8.0%;
IC, 3.0%; diabetes, 10.3%; and HLA-A*29, B*44 positivity, 9.7%. Prevalences of
female sex; chronic fatigue; IC; and HLA-A*29, B*44 positivity were greater in
patients with fibromyalgia. Logistic regression on fibromyalgia revealed three
positive associations: chronic fatigue (p=0.0149; odds ratio 2.6 [95% confidence
interval 1.2, 5.6]); Sjogren's syndrome (p=0.0004; 5.2 [2.1, 13.2]); and IC
(p=0.0232; 5.7 [1.3, 25.7]). In an analysis of covariance, there were significant
interactions of chronic fatigue, Sjogren's syndrome, and interstitial cystitis on
fibromyalgia. CONCLUSIONS: Fibromyalgia is common in non-Hispanic white adult
index patients with primary immunodeficiency, especially women. Chronic fatigue,
Sjogren's syndrome, and IC are significantly associated with fibromyalgia after
adjustment for other independent variables.
PMID- 28422001
TI - Microscopic polyangiitis and non-HBV polyarteritis nodosa with poor-prognosis
factors: 10-year results of the prospective CHUSPAN trial.
AB - OBJECTIVES: To analyse the 10-year outcomes of 64 patients with non-HBV
polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) and Five-Factor
Score-defined poor-prognosis factors enrolled (1994-2000) in the prospective,
randomised, open-label CHUSPAN trial. METHODS: The 64 patients were randomised to
receive 12 (33: 23 MPA, 10 PAN) or 6 (31: 17 MPA, 14 PAN) cyclophosphamide (CYC)
pulses combined with glucocorticoids. Ten-year follow-up of these patients
included times to relapse(s), failure(s) and/or deaths calculated from treatment
onset. Data were censored after 120 months of follow-up. RESULTS: Eleven patients
were lost to-follow-up (mean+/-SD follow-up: 61.9+/-35.2 months), with no between
group difference. As previously reported, baseline clinical characteristics and
laboratory values were comparable for the 2 groups. After induction, 53/64 (83%)
entered remission, with comparable percentages for both groups. The regimen was
intensified for 11 initial non-responders: 4 achieved remission and 8 died before
doing so. During extended follow-up, 26 patients experienced >=1 relapse(s): 12
in the 12-pulse group and 14 in the 6-pulse group (p=0.47). At 10 years, overall
and disease-free survival rates were 57.4% and 29.9%, with no between-group
differences (p=0.185 and p=0.367, respectively). Factors associated with shorter
disease-free survival were age >=65 years and alveolar haemorrhage at diagnosis.
CONCLUSIONS: Although the 3-year CHUSPAN trial results indicated the superiority
of 12 vs. 6 CYC pulses, that early advantage progressively declined and became
non-significant by 10 years.
PMID- 28422002
TI - Treatment of psoriasis with ustekinumab improved skin tightening in systemic
sclerosis.
AB - Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by
fibrosis, inflammation and vasculopathy in the skin and internal organs.
Recently, several articles described that Th17 cells, IL-23 and IL-17 levels were
significantly elevated in the peripheral blood or fibrotic sites of SSc. We
report a case of SSc and psoriasis administered ustekinumab, IL-12/IL-23
inhibitor. In this case, the skin tightening was successfully improved and
ustekinumab was more effective, even though oral prednisolone (9-12 mg/day) had
some effect on skin tightening and arthralgia. We consider that inhibition of
Th17 cytokines may lead to therapeutic efficacy against SSc. Ustekinumab has the
potential for a treatment option of SSc.
PMID- 28422003
TI - Efficacy and safety of leflunomide as an adjuvant drug in refractory
dermatomyositis with primarily cutaneous activity.
AB - OBJECTIVES: To evaluate leflunomide as an adjuvant drug in refractory
dermatomyositis (DM) with primarily cutaneous activity. METHODS: A retrospective,
single-centre, cohort study including 18 adult patients with DM (classical or
clinically amyopathic DM) and cutaneous activity from 2001 to 2016 was conducted.
Patients were dependent on glucocorticoid and refractory to at least two full
dose immunosuppressants/immunomodulators or presented previous adverse events
with immunobiological drugs. One immunosuppressant was maintained and leflunomide
added to the treatment. Patients were followed for six consecutive months.
RESULTS: Leflunomide proved effective and safe in 12 (66.6%) out of the 18
patients. There was total control of cutaneous activity and prednisone was
tapered from 17.5 to 6.0 mg/day (p<0.001). In addition, two of these patients
that also had muscle involvement improved muscle strength after leflunomide
treatment. Side effects or inefficacy were observed in six patients. There were
no cases of serious infection or death. CONCLUSIONS: Leflunomide therapy appears
to be effective and safe as an adjuvant drug in refractory DM with primarily
cutaneous activity. Further studies are needed to confirm this data.
PMID- 28422004
TI - Performance of influenza case definitions for influenza community surveillance:
based on the French influenza surveillance network GROG, 2009-2014.
AB - International case definitions recommended by the Centers for Disease Control and
Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC),
and the World Health Organization (WHO) are commonly used for influenza
surveillance. We evaluated clinical factors associated with the laboratory
confirmed diagnosis of influenza and the performance of these influenza case
definitions by using a complete dataset of 14,994 patients with acute respiratory
infection (ARI) from whom a specimen was collected between August 2009 and April
2014 by the Groupes Regionaux d'Observation de la Grippe (GROG), a French
national influenza surveillance network. Cough and fever >= 39 degrees C most
accurately predicted an influenza infection in all age groups. Several other
symptoms were associated with an increased risk of influenza (headache, weakness,
myalgia, coryza) or decreased risk (adenopathy, pharyngitis, shortness of breath,
otitis/otalgia, bronchitis/ bronchiolitis), but not throughout all age groups.
The WHO case definition for influenza-like illness (ILI) had the highest
specificity with 21.4%, while the ECDC ILI case definition had the highest
sensitivity with 96.1%. The diagnosis among children younger than 5 years remains
challenging. The study compared the performance of clinical influenza definitions
based on outpatient surveillance and will contribute to improving the
comparability of data shared at international level.
PMID- 28422005
TI - Blood donor screening for West Nile virus (WNV) revealed acute Usutu virus (USUV)
infection, Germany, September 2016.
AB - Between 1 June and 31 December 2016, 13,023 blood donations from the University
Hospital Aachen in Germany were routinely screened for West Nile virus (WNV) RNA
using the cobas TaqScreen WNV Test. On 28 September 2016, one blood donor was
tested positive. Subsequent analysis revealed an acute Usutu virus (USUV)
infection. During the ongoing USUV epizootics in Germany, blood transfusion
services, public health authorities and clinicians should be aware of increased
human USUV infections.
PMID- 28422006
TI - ECDC Round Table Report and ProMed-mail most useful international information
sources for the Netherlands Early Warning Committee.
AB - The Netherlands Early Warning Committee (NEWC) aims to identify infectious
diseases causing a potential threat to Dutch public health. Threats are assessed
and published as (information) alerts for public health experts. To identify
threats from abroad, the NEWC screens 10 sources reporting disease outbreaks each
week. To identify the sources essential for complete and timely reporting, we
retrospectively analysed 178 international alerts published between 31 January
2013 and 30 January 2014. In addition, we asked the four NEWC coordinators about
the required time to scan the information sources. We documented the date and
source in which the signal was detected. The ECDC Round Table (RT) Report and
ProMED-mail were the most complete and timely sources, reporting 140 of 178 (79%)
and 121 of 178 (68%) threats respectively. The combination of both sources
reported 169 (95%) of all threats in a timely manner. Adding any of the other
sources resulted in minor increases in the total threats found, but considerable
additional time investment per additional threat. Only three potential relevant
threats (2%) would have been missed by only using the ECDC RT Report and ProMed
mail. We concluded that using only the ECDC RT Report and ProMed-mail to identify
threats from abroad maintains a sensitive Early Warning System.
PMID- 28422007
TI - High risk of dengue type 2 outbreak in French Polynesia, 2017.
AB - In French Polynesia, the four serotypes of dengue virus (DENV-1 to -4) have
caused 14 epidemics since the mid-1940s. From the end of 2016, an increasing
number of Pacific Island Countries and Territories have reported DENV-2 outbreaks
and in February 2017, DENV-2 infection was detected in French Polynesia in three
travellers from Vanuatu. As DENV-2 has not been circulating in French Polynesia
since December 2000, there is high risk for an outbreak to occur.
PMID- 28422008
TI - Arabidopsis 14-3-3 epsilon members contribute to polarity of PIN auxin carrier
and auxin transport-related development.
AB - Eukaryotic 14-3-3 proteins have been implicated in the regulation of diverse
biological processes by phosphorylation-dependent protein-protein interactions.
The Arabidopsis genome encodes two groups of 14-3-3s, one of which - epsilon - is
thought to fulfill conserved cellular functions. Here, we assessed the in vivo
role of the ancestral 14-3-3 epsilon group members. Their simultaneous and
conditional repression by RNA interference and artificial microRNA in seedlings
led to altered distribution patterns of the phytohormone auxin and associated
auxin transport-related phenotypes, such as agravitropic growth. Moreover, 14-3-3
epsilon members were required for pronounced polar distribution of PIN-FORMED
auxin efflux carriers within the plasma membrane. Defects in defined post-Golgi
trafficking processes proved causal for this phenotype and might be due to lack
of direct 14-3-3 interactions with factors crucial for membrane trafficking.
Taken together, our data demonstrate a fundamental role for the ancient 14-3-3
epsilon group members in regulating PIN polarity and plant development.
PMID- 28422011
TI - The future of the NHS.
PMID- 28422009
TI - Axon tension regulates fasciculation/defasciculation through the control of axon
shaft zippering.
AB - While axon fasciculation plays a key role in the development of neural networks,
very little is known about its dynamics and the underlying biophysical
mechanisms. In a model system composed of neurons grown ex vivo from explants of
embryonic mouse olfactory epithelia, we observed that axons dynamically interact
with each other through their shafts, leading to zippering and unzippering
behavior that regulates their fasciculation. Taking advantage of this new
preparation suitable for studying such interactions, we carried out a detailed
biophysical analysis of zippering, occurring either spontaneously or induced by
micromanipulations and pharmacological treatments. We show that zippering arises
from the competition of axon-axon adhesion and mechanical tension in the axons,
and provide the first quantification of the force of axon-axon adhesion.
Furthermore, we introduce a biophysical model of the zippering dynamics, and we
quantitatively relate the individual zipper properties to global characteristics
of the developing axon network. Our study uncovers a new role of mechanical
tension in neural development: the regulation of axon fasciculation.
PMID- 28422010
TI - Synaptic input sequence discrimination on behavioral timescales mediated by
reaction-diffusion chemistry in dendrites.
AB - Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key
computational operations, including pattern recognition, event prediction, and
plasticity, involve neural discrimination of spatio-temporal sequences. Here, we
show that synaptically-driven reaction-diffusion pathways on dendrites can
perform sequence discrimination on behaviorally relevant time-scales. We used
abstract signaling models to show that selectivity arises when inputs at
successive locations are aligned with, and amplified by, propagating chemical
waves triggered by previous inputs. We incorporated biological detail using
sequential synaptic input onto spines in morphologically, electrically, and
chemically detailed pyramidal neuronal models based on rat data. Again, sequences
were recognized, and local channel modulation downstream of putative sequence
triggered signaling could elicit changes in neuronal firing. We predict that
dendritic sequence-recognition zones occupy 5 to 30 microns and recognize time
intervals of 0.2 to 5 s. We suggest that this mechanism provides highly parallel
and selective neural computation in a functionally important time range.
PMID- 28422012
TI - Syphilis: an ancient disease in a modern era.
PMID- 28422013
TI - Defunding the UNFPA: sign of the times.
PMID- 28422014
TI - Palliative care in humanitarian crises: always something to offer.
PMID- 28422015
TI - Offline: When The Lancet went to the Vatican.
PMID- 28422016
TI - Syria chemical attacks: preparing for the unconscionable.
PMID- 28422018
TI - Accounting for polio survivors in the post-polio world.
PMID- 28422017
TI - Research needed to prevent MERS coronavirus outbreaks.
PMID- 28422019
TI - Health systems resilience: meaningful construct or catchphrase?
PMID- 28422020
TI - Private water operators' contribution to realising the right to water.
PMID- 28422021
TI - Prevention of early-onset pre-eclampsia.
PMID- 28422022
TI - Maternal deaths and humanitarian crises.
PMID- 28422023
TI - Prevention of early-onset pre-eclampsia - Authors' reply.
PMID- 28422024
TI - Prolonged glucocorticoid treatment in acute respiratory distress syndrome.
PMID- 28422025
TI - Prolonged glucocorticoid treatment in acute respiratory distress syndrome -
Authors' reply.
PMID- 28422026
TI - Beyond ESPAC-4: better surgery and systemic therapy.
PMID- 28422027
TI - Stoop to conquer: preventing stroke and dementia together.
PMID- 28422028
TI - Department of Error.
PMID- 28422029
TI - Interpreting Treatment-Related Changes Using the Tinnitus Questionnaire in
Argstatter H, Grapp M, Plinkert PK, Bolay HV. Heidelberg Neuro-Music Therapy for
Chronic-tonal Tinnitus - Treatment Outline and Psychometric Evaluation. Int
Tinnitus J 2012;17(1):31-41.
PMID- 28422030
TI - Analysis of Hearing and Tinnitus in Workers Exposed to Occupational Noise.
AB - INTRODUCTION: Noise is one of the harmful agents to health that is present in the
various branches of economic activity. Hearing loss and tinnitus are among the
most frequently reported complaints by workers exposed to occupational noise.
OBJECTIVE: To analyze the hearing and tinnitus in normal-hearing workers exposed
to occupational noise. METHODS: This is a cross-sectional analytical trial in
metallurgical industries, in which we evaluated normal-hearing workers through
anamnesis, audiometry and otoacoustic emissions. RESULTS: It was observed high
prevalence of failure of otoacoustic emissions (40%) and tinnitus (66.6%). Both
in the amplitude and in the signal-to-noise ratio, the higher is the frequency of
the sound, the worse the results. Despite having audiometry within normal limits,
the results indicate that workers are suffering the effects of exposure and
reveals association between failure of otoacoustic emissions and tinnitus in this
population (X2 = 6,732). CONCLUSION: It is concluded that failures in DPOAE and
tinnitus are predictors of hearing damage in normal-hearing workers.
PMID- 28422031
TI - The Importance of Labyrinthine Examination in the Prognosis and Therapy for
Balance in Spinocerebellar Ataxia.
AB - INTRODUCTION: Spinocerebellar ataxias (SCAs) are a heterogeneous group of
neurodegenerative diseases that are characterized by the presence of progressive
cerebellar ataxia. OBJECTIVE: Identify vestibular disorders and demonstrate the
importance of labyrinthine examination in the prognosis and therapy for balance
in patients with SCAs. MATERIALS AND METHODS: The study had a retrospective cross
sectional design and evaluated 57 patients, mean age of 41.6 years and standard
deviation of 13 years. Patients underwent the following procedures: anamnesis,
ENT examination and vestibular exam using electronystagmography (ENG). RESULTS:
The most frequent complaints were gait imbalance (71.9%), dysarthria (49.1%),
dizziness (43.8%) and dysphagia (36.8%). 84.2% of the tests showed alterations.
The most common tests with alterations were the caloric test (78.9%), slow
saccades (61.4%) and the rotating chair test (49.1%). CONCLUSION: The clinical
history of the patient and oculomotor alterations in the labyrinthine examination
provide sufficient information for the proper use of virtual rehabilitation
protocols in the treatment of imbalance, making it the most effective therapy
method. It was evident that changes in ENG are related to the severity of the SCA
or the clinical stage of the disease. The labyrinthine examination proved to be
an important concomitant tool to clinical and genetic study.
PMID- 28422032
TI - A Tribute to Robert W. Entenmann (Bob)-12/10/16.
PMID- 28422033
TI - [Values and significances of the XX Century Medicine.]
PMID- 28422034
TI - Endocrine disruptors and prostate cancer.
AB - OBJECTIVES: Although prostate cancer is probably the most frequent cancer in men,
little is known about its etiology. Clear evidence exists about variations in the
incidence of prostate cancer between populations living in different countries.
These variations could be explained by differences in lifestyle and a possible
association with a set of substances that are able to intervene in the origin of
the disease. METHODS: The reason that lifestyle may be the cause of prostate
cancer is related to endocrine disruptors. These are a group of chemical
substances that can mimic or alter hormone signaling. These disruptors are able
to exert their effect at very low doses and act insidiously over the years, even
being able to pass their effect on from one generation to the next. Cholesterol
is an essential precursor in the synthesis of androgens, estrogens and other
substances that are active in prostate cancer. Cholesterol is a central
metabolite in lipid metabolism, the inflammatory response and other elements
involved in the formation and progression of cancer. High cholesterol
concentrations can give rise to the accumulation of androgens in tumor cells.
Additionally, endocrine disruptors have been identified as being responsible for
processes related with fertility, genital malformations and various
hormonedependent cancers. Disruptors already identified include
diethylstilbestrol, dichlorodiphenyltrichloroethane (DDT), polychlorinated
biphenyls and dioxins. RESULTS: Though no clear direct association has yet been
found in humans between most endocrine disruptors and prostate cancer, evidence
suggests that an inadequate diet and contact with certain toxic agents
predisposes to the disease. These disruptors are known to be especially relevant
at particular times, such as during pregnancy, neonatal stages and puberty.
CONCLUSIONS: The problem with these toxic agents is that their peculiarities and
way of acting over time make their study difficult. Nonetheless, research must be
encouraged given their importance.
PMID- 28422035
TI - [New therapeutic schedules of Sunitinib: Current evidence regarding the 2:1
scheme.]
AB - INTRODUCTION: In 2006, sunitinib approval by the FDA was a real revolution for
the treatment of metastatic renal cell carcinoma (mRCC). However, considerable
rates of dose reductions and therapeutic suppressions with the standard regimen
(4:2) have forced the search for new schedule proposals in order to optimize the
balance between side effects and oncologic efficacy. Among these new proposals,
the 2:1 scheme is the one that has generated more expectations. OBJECTIVE: The
objective of this paper is to make a review and critical discussion of current
evidence about the new schedules of treatment with sunitinib. METHODS:
Unstructured review of the literature on the various therapeutic regimens with
sunitinib, making a comparison in terms of progression-free survival (PFS),
overall survival (OS) and toxicity. RESULTS: We summarize the data from all
relevant studies published to date comparing the standard 4:2 schedule versus the
new 2:1. Most patients treated with 2:1 scheme are grouped in three retrospective
observational studies and mostly correspond to patients who were initially
treated with a 4:2 scheme and then moved to 2:1. A phase II randomized clinical
trial comparing 4:2 and 2:1 schemes from the beginning has also been conducted.
None of these studies found significant differences between the two regimens in
terms of PFS or OS. Regarding the toxicity profile, the 2:1 scheme has proved to
be more advantageous than the 4:2. CONCLUSIONS: Despite the still limited amount
of data, current evidence supports the use of a 2:1 schedule, as it provides
patients substantial advantages because of its better tolerability profile,
without a loss in oncological efficacy. Currently, the 2:1 scheme is an
appropriate alternative therapeutic strategy, especially in patients with poor
tolerance to the standard 4:2 regimen.
PMID- 28422036
TI - Physicochemical factors of the urine of children with hypercalciuria.
AB - OBJECTIVE: Hypercalciuria is a common lithogenic risk factor. The aim of this
study was, first, to study the characteristics of urine biochemical factors of
children with hypercalciuria (HC) and compare them with those of children without
hypercalciuria. Second, to analyze the differences between children with HC and
lithiasis (HCL) and children with HC and no lithiasis (HCNL). METHODS: The sample
was composed by 111 cases with HC, divided into 2 groups: HCNL group, consisting
of 93 cases with no personal history of kidney stones, and HCL group, 18 cases
with personal history of kidney stones. As a cohort control group, 113 healthy
children were used. Creatinine, urea, sodium, potassium, chlorine, uric acid,
calcium, phosphorus, magnesium and osmolality: blood and 24-hour urine following
parameters were determined. Oxalate and citrate were determined in urine.
RESULTS: The mean values of natriuresis, uricosuria, phosphaturia, magnesuria,
citraturia, calcium oxalate and calcium phosphate saturation were higher in HCNL
than in control group. The HCL group had phosphaturia, calcium oxalate and
calcium phosphate saturations more elevated compared with the control group.
There were no significant differences in urinary excretion of various parameters
when the groups HCL and HCNL were compared. CONCLUSIONS: Our results show that
children with hypercalciuria without lithiasis associated show an increase in
natriuresis, phosphaturia, uricosuria, magnesuria and citraturia. We found no
differences between these urinary abnormalities when compared hypercalciuric
children without lithiasis with those with hypercalciuria and urolithiasis.
PMID- 28422037
TI - Ureteral meatotomy as an option in the management of primary obstructive
megaureter in neonates and infants.
AB - : Differentiating between the cases of megaureter that require surgery and the
ones in whom treatment can be delayed is challenging. A large number of surgical
techniques for the treatment of POM been proposed aiming mainly to reduce renal
damage by relieving the affected ureter. Resection of the affected ureteral
segment followed by vesicoureteral reimplantation either with or without
reduction ureteroplasty is the classic treatment, however posing a high rate of
complications when performed in patients aged less than one year. Endoscopic
techniques have also been described to avoid external diversion. Recently,
refluxing ureteral reimplantation has been proposed as a temporary treatment for
patients with POM. OBJECTIVE: To describe the ureteral meatotomy technique as an
alternative to the refluxing ureteral reimplantation for POM in patients aged
less than one year. METHOD: Retrospective study of patients with POM undergoing
ureteral meatotomy, aiming to temporarily relieve the ureter. The procedure
consists of a 1.5 cm-long cut made with scissors on the upper edge of the
ureteral ostium at the 12 o'clock position, until the dilated portion of the
ureter was found and abundant urine drainage was observed. The edges of the
incision were sutured, joining together the ureteral mucosa and the bladder
mucosa. RESULT: From 2011 to 2015, three patients with POM underwent ureteral
meatotomy, with four renal units treated altogether. None of the patients
presented complications and, as a sign of obstruction relief, all showed reduced
dilatation at the ultrasound. No patient had complications. CONCLUSIONS: Ureteral
meatotomy is a safe and effective technique in the initial treatment of POM in
patients aged less than one year.
PMID- 28422038
TI - Treatment of urachal disorders: The open and laparoscopic surgery approach.
AB - INTRODUCTION: The present study analyzes cases of urachal abnormalities treated
with laparoscopic approach in our hospital. CASE DESCRIPTION: A retrospective
descriptive study of urachal disorders with laparoscopic surgery approach
performed at our hospital in the period 1999-2015. Patients' clinical data are
presented (radiological findings, surgical data, pathology findings,
complications and a follow-up of each patient). RESULTS: 7 Adults presented
complicated urachal disorders treated laparoscopically. The average age was 43.1
years old (DE +/-11). The mean surgical time of laparoscopic management was 154.2
minutes (range 120-240). Mean hospital stay was 4.9 days (DE +/-1.1). There were
no early or late postoperative complications. CONCLUSION: Laparoscopic removal of
urachal remnants is a safe and reproducible technique.
PMID- 28422039
TI - [Urinary tract lymphoepithelial carcinoma. Report of two cases and bibliographic
review.]
AB - OBJECTIVE: We report two cases of patients diagnosed with lymphoepithelioma-like
carcinomas of the urinary tract. We review the literature of this rare entity.
The objective is to clarify the clinical and therapeutic characteristics.
METHODS: We present a retrospective review of medical records of two patients
diagnosed with lymphoepithelioma-like carcinomas, one in the renal pelvis and the
other in the bladder. We review the epidemiology, diagnosis and therapeutic
alternatives. RESULTS: Case 1: A 74-year-old women with past medical history of
left radical nephrectomy and retroperitoneal lymphadenectomy six years before for
renal pelvis carcinoma type pure lymphoepithelioma-like, stage pT4R0pN1cM0. She
received adjuvant chemotherapy with Cisplatin and Gemcitabine. Five years later,
she presented tumor recurrence in the left ureteral meatus, this lesion was
resected. The pathology reported a high-grade urothelial carcinoma with marked
lymphoid component, stage pT1. At follow-up, one year after the last recurrence,
the patient was asymptomatic. In tomography control, no local or distant
recurrences were objectified. Case 2: A 82-year-old men with diagnosis of
muscleinvasive bladder cancer. The tumor caused right obstructive uropathy
without extracapsular, regional or remote extension. We performed a radical
cystoprostatectomy with bilateral pelvic lymphadenectomy and urinary diversion
type cutaneous transureterostomy. The pathology reported a urothelial bladder
carcinoma type mixed lymphoepithelioma-like, stage pT4aR1pN2cM0. At six months
follow-up, the patient had liver and spleen lesions and retroperitoneal
adenopathic nodes, all suggestive of metastases. He is currently receiving
symptomatic treatment of their disease. CONCLUSIONS: We emphasize the clinical
importance involved in the diagnosis of this entity. The diagnosis influence the
aggressiveness of treatment and disease-specific survival. Therefore, concomitant
transitional cell carcinoma defines the prognosis. The role of
immunohistochemical staining is fundamental, allowing us to confirm the presence
of the epithelial component.
PMID- 28422040
TI - Carcinoma of the penis.
PMID- 28422041
TI - Image diagnosis of emphysematous cystitis.
PMID- 28422042
TI - Synchronous penoscrotal implantation of penile prosthesis and artificial urinary
sphincter after radical prostatectomy.
AB - OBJECTIVES: To evaluate the results of synchronous dual implantation of penile
(PP) and artificial urinary sphincter prosthesis (AUSP) in patients with severe
erectile dysfunction (ED) and urinary incontinence (UI) after radical
prostatectomy (RP). METHODS: Between January 2006 and March 2015, patients who
underwent synchronous dual implantation of PP for severe post-RP ED and AUSP for
moderate to severe post-RP UI in our clinic were screened retrospectively. The
erectile function and the continence status were evaluated by the questionnaires
of IIEF-5 and ICIQ-SF. Results for the preoperative period and for the 1st
postoperative year were revealed from patient charts. Long term results were
evaluated by telephone interviews. Comorbidities, infection rates and
complications were noted. RESULTS: A total of 14 patients underwent synchronous
dual implantation; out of which, 11 had a long enough follow up period for a
sufficient long term evaluation. 3/11 had MPP and 8/11 had two-piece IPP
implantation together with an AUSP. All of the implantations were carried out
through an upper transverse scrotal incision. Mean follow up time was 61.3 +/- 20
months. In 1 patient who had received adjuvant radiotherapy, both of the devices
were removed due to infection and cuff erosion. Mean daily usage of pads
diminished from 4 to 1 while ICIQ-SF score decreased from 19 to 2 and IIEF-5
score increased from 3 to 23. CONCLUSION: Synchronous implantation of PP and AUSP
is a safe and effective treatment option for patients with severe ED and moderate
to severe UI after RP.
PMID- 28422043
TI - Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir,
dasabuvir +/- ribavirin for hepatitis C genotype 1 - final results of the REV1TAL
study.
AB - BACKGROUND: Limited data exist on the outcomes of ritonavir-boosted paritaprevir
with ombitasvir and dasabuvir (PrOD) +/- ribavirin in a real-world setting. The
aim of this study was to compare the efficacy and safety of PrOD-based therapy in
hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre
treatment factors predictive of sustained viral response (SVR) and serious
adverse events (SAEs) on treatment. METHODS: 451 patients with hepatitis C
genotype 1 treated in 20 centres across Australia were included. Baseline
demographic, clinical and laboratory information, on-treatment biochemical,
virological and haematological indices and details on serious adverse events were
collected locally. RESULTS: Cirrhosis was present in 340 patients (75.4%).
Overall SVR was 95.1% with no differences in SVR between the cirrhosis and non
cirrhosis groups (94.7% versus 96.4%). SVR in subgenotypes 1a and 1b was 93.1%
and 99.2%, respectively. On multivariate analysis, baseline bilirubin level and
early treatment cessation predicted SVR. SAEs occurred in 10.9% of patients
including hepatic decompensation (2.7%) and hepatocellular carcinoma (1.8%). On
multivariate analysis of factors predictive of SAEs in the overall group, Child
Turcotte-Pugh (CTP) B was the only significant factor, while in those with
cirrhosis, baseline albumin and creatinine levels were significant. CONCLUSIONS:
In this large real-world cohort of HCV genotype 1 subjects, treatment with PrOD
was highly effective and similar to clinical trials. Important determinants of
reduced SVR include early cessation of therapy and baseline bilirubin
concentration. SAEs were not infrequent with CTP B patients being at greatest
risk.
PMID- 28422044
TI - Design of flexible PANI-coated CuO-TiO2-SiO2 heterostructure nanofibers with high
ammonia sensing response values.
AB - We report a room-temperature ammonia sensor with extra high response values and
ideal flexibility, including polyaniline (PANI)-coated titanium dioxide-silicon
dioxide (TiO2-SiO2) or copper oxide-titanium dioxide-silicon dioxide (CuO-TiO2
SiO2) composite nanofibers. Such flexible inorganic TiO2-SiO2 and CuO-TiO2-SiO2
composite nanofibers were prepared by electrospinning, followed by calcination.
Then, in situ polymerization of aniline monomers was carried out with inorganic
TiO2-SiO2 and CuO-TiO2-SiO2 composite nanofibers as templates. Gas sensing tests
at room temperature indicated that the obtained CuO-TiO2-SiO2/PANI composite
nanofibers had much higher response values to ammonia gas (ca. 45.67-100 ppm)
than most of those reported before as well as the prepared TiO2-SiO2/PANI
composite nanofibers here. These excellent sensing properties may be due to the P
N, P-P heterojunctions and a structure similar to field-effect transistors formed
on the interfaces between PANI, TiO2, and CuO, which is p-type, n-type, and p
type semiconductor, respectively. In addition, the prepared free-standing CuO
TiO2-SiO2/PANI composite nanofiber membrane was easy to handle and possessed
ideal flexibility, which is promising for potential applications in wearable
sensors in the future.
PMID- 28422045
TI - Sequential reduction of the silicon single-electron transistor structure to
atomic scale.
AB - Here we present an original CMOS compatible fabrication method of a single
electron transistor structure with extremely small islands, formed by solitary
phosphorus dopants in the silicon nanobridge. Its key feature is the controllable
size reduction of the nanobridge in sequential cycles of low energy isotropic
reactive ion etching that results in a decreased number of active charge centers
(dopants) in the nanobridge from hundreds to a single one. Electron transport
through the individual phosphorous dopants in the silicon lattice was studied.
The final transistor structure demonstrates a Coulomb blockade voltage of ~30 mV
and nanobridge size estimated as [Formula: see text]. Analysis of current
stability diagrams shows that electron transport in samples after the final
etching stage had a single-electron nature and was carried through three
phosphorus atoms. The fabrication method of the demonstrated structure allows it
to be modified further by various impurities in additional etching and
implantation cycles.
PMID- 28422046
TI - Nanowelding and patterning of silver nanowires via mask-free atmospheric cold
plasma-jet scanning.
AB - Silver nanowire (AgNW) thin film is a promising candidate to replace traditional
indium tin oxide in optoelectronics applications. To date however, the widespread
application of AgNW thin film is limited by the weak point contacts between
individual AgNWs and the lack of facile patterning techniques. Here, we
demonstrate a novel and facile method to not only nanoweld AgNW junctions but
also pattern AgNW thin films via mask-free cold plasma-jet scanning in ambient
conditions. After the plasma-jet nanowelding treatment, the morphology of AgNWs
change substantially and the junctions are welded together. The nanowelded AgNWs
based thin film shows enhanced electrical and mechanical properties. On the other
hand, after the plasma-jet patterning treatment, the AgNWs are etched and
transformed into separated large particles. Different kinds of patterns are
produced via this patterning technique. At last, a simple light emitting diode
circuit is fabricated to demonstrate the suitability of the nanowelded and
patterned AgNW electrodes for flexible electronic devices.
PMID- 28422047
TI - Template for the neural control of directed stepping generalized to all legs of
MantisBot.
AB - We previously developed a neural controller for one leg of our six-legged robot,
MantisBot, that could direct locomotion toward a goal by modulating leg-local
reflexes with simple descending commands from a head sensor. In this work, we
successfully apply an automated method to tune the control network for all three
pairs of legs of our hexapod robot MantisBot in only 90 s with a desktop
computer. Each foot's motion changes appropriately as the body's intended
direction of travel changes. In addition, several results from studies of walking
insects are captured by this model. This paper both demonstrates the broad
applicability of this control method for robots, and suggests neural mechanisms
underlying observations from walking insects.
PMID- 28422048
TI - SAK-HV Decreases the Self-Ubiquitination of MEKK1 to Promote Macrophage
Proliferation via MAPK/ERK and JNK Pathways.
AB - SAK-HV is an anti-atherosclerosis recombinant fusion protein developed by our
lab. Our study determined that SAK-HV promoted macrophage proliferation, of which
the mechanism was explored by both RAW264.7 cells and primary macrophages. Mass
spectrometric analysis and co-immunoprecipitation were combined to screen the SAK
HV-interacting proteins in RAW264.7 cells. Confocal microscopy was adopted to
detect the localization of SAK-HV in cells. The results indicated that SAK-HV
triggered macrophage proliferation via the mitogen-activated protein kinase
(MAPK)/extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases
(JNK) pathways by its SAK-mutant functional domain. We screened out Uba1 as the
SAK-HV-interacting protein in the RAW264.7 cells and discovered their co
localization in the cytoplasm and nucleus. Inhibiting Uba1 significantly
decreased the SAK-HV-induced macrophage proliferation. Thus, we postulated an
attractive model of ubiquitination, in which the interactions between Uba1 and
specific E2 enzymes are blocked by its interaction with SAK-HV. Based on this
model, we detected the decreased self-ubiquitination of MEKK1 after SAK-HV
treatment and concluded that SAK-HV inhibits the self-ubiquitination of MEKK1 via
its SAK-mutant functional domain to activate MAPK/ERK and JNK pathways, promoting
macrophage proliferation. This conclusion highly supported our hypothesized model
of ubiquitination at the level of Uba1, which may represent a novel paradigm to
promote macrophage proliferation by using the E1 enzyme (Uba1) as a switch.
PMID- 28422049
TI - Regulation of Anthocyanin Biosynthesis in Purple Leaves of Zijuan Tea (Camellia
sinensis var. kitamura).
AB - Plant anthocyanin biosynthesis is well understood, but the regulatory mechanism
in purple foliage tea remains unclear. Using isobaric tag for relative and
absolute quantification (iTRAQ), 815 differential proteins were identified in the
leaves of Zijuan tea, among which 20 were associated with the regulation of
anthocyanin metabolism. We found that the abundances of anthocyanin synthesis
related enzymes such as chalcone synthase, chalcone isomerase, dihydroflavonol 4
reductase and anthocyanin synthetase, as well as anthocyanin accumulation-related
UDP-glucosyl transferase and ATP-binding cassette (ABC) transporters in the
purple leaves were all significantly higher than those in the green leaves. The
abundances of the transcription factors bHLH and HY5, regulating anthocyanin
biosynthesis at transcriptional level were also obviously higher in purple leaves
than those in green leaves. In addition, bifunctional 3-dehydroquinate
dehydratase and chorismate mutase in purple leaves were distinctly higher in
abundance compared to green leaves, which provided sufficient phenylalanine
substrate for anthocyanin synthesis. Furthermore, lignin synthesis was found to
be reduced due to the lower abundances of cinnamoyl-CoA reductase 1, peroxidase
15 and laccase-6, which resulted in increase of intermediates flow into
anthocyanin synthesis pathway. The physiological data were consistent with
proteomic results. These four aspects of biosynthetic regulation contribute to
anthocyanin accumulation in purple leaves of Zijuan tea.
PMID- 28422050
TI - K-mer Content, Correlation, and Position Analysis of Genome DNA Sequences for the
Identification of Function and Evolutionary Features.
AB - In genome analysis, k-mer-based comparison methods have become standard tools.
However, even though they are able to deliver reliable results, other algorithms
seem to work better in some cases. To improve k-mer-based DNA sequence analysis
and comparison, we successfully checked whether adding positional resolution is
beneficial for finding and/or comparing interesting organizational structures. A
simple but efficient algorithm for extracting and saving local k-mer spectra
(frequency distribution of k-mers) was developed and used. The results were
analyzed by including positional information based on visualizations as genomic
maps and by applying basic vector correlation methods. This analysis was
concentrated on small word lengths (1 <= k <= 4) on relatively small viral
genomes of Papillomaviridae and Herpesviridae, while also checking its usability
for larger sequences, namely human chromosome 2 and the homologous chromosomes
(2A, 2B) of a chimpanzee. Using this alignment-free analysis, several regions
with specific characteristics in Papillomaviridae and Herpesviridae formerly
identified by independent, mostly alignment-based methods, were confirmed.
Correlations between the k-mer content and several genes in these genomes have
been found, showing similarities between classified and unclassified viruses,
which may be potentially useful for further taxonomic research. Furthermore,
unknown k-mer correlations in the genomes of Human Herpesviruses (HHVs), which
are probably of major biological function, are found and described. Using the
chromosomes of a chimpanzee and human that are currently known, identities
between the species on every analyzed chromosome were reproduced. This
demonstrates the feasibility of our approach for large data sets of complex
genomes. Based on these results, we suggest k-mer analysis with positional
resolution as a method for closing a gap between the effectiveness of alignment
based methods (like NCBI BLAST) and the high pace of standard k-mer analysis.
PMID- 28422053
TI - Erratum: Wong, L.P., et al. The Self-Regulation Model of Illness: Comparison
between Zika and Dengue and Its Application to Predict Mosquito Prevention
Behaviours in Malaysia, a Dengue-Endemic Country Int. J. Environ. Res. Public
Health 2016, 13, 1210.
AB - n/a.
PMID- 28422052
TI - Folic Acid Reduces Tau Phosphorylation by Regulating PP2A Methylation in
Streptozotocin-Induced Diabetic Mice.
AB - High incidence rate of Alzheimer's disease (AD) is observed in patients with type
2 diabetes. Aggregated beta-amyloid (Abeta) and hyperphosphorylated tau are the
hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as
well as in diabetic patients. Folates mediate the transfer of one carbon unit,
required in various biochemical reactions. The effect of folate on tau
phosphorylation in diabetic models still remains unknown. In this study, we
investigated the effect and mechanism of folic acid on hyperphosphorylation of
tau in streptozotocin (STZ)-induced diabetic mice. Diabetic mice induced by STZ,
at the age of 10 weeks, were administered with three levels of folic acid: folic
acid-deficient diet, diet with normal folic acid content, and 120 MUg/kg folic
acid diet for 8 weeks. Levels of serum folate and blood glucose were monitored.
Tau phosphorylation, protein phosphatase 2A (PP2A) methylation, and Glycogen
synthase kinase 3beta (GSK-3beta) phosphorylation were detected using Western
blot. The S-adenosyl methionine:S-adenosyl homocysteine ratio (SAM:SAH) in brain
tissues was also determined. DNA methyltransferase (DNMT) mRNA expression levels
were detected using real-time PCR. Folic acid reduced tau hyperphosphorylation at
Ser396 in the brain of diabetes mellitus (DM) mice. In addition, PP2A methylation
and DNMT1 mRNA expression were significantly increased in DM mice post folic acid
treatment. GSK-3beta phosphorylation was not regulated by folic acid
administration. Folic acid can reduce tau phosphorylation by regulating PP2A
methylation in diabetic mice. These results support that folic acid can serve as
a multitarget neuronal therapeutic agent for treating diabetes-associated
cognitive dysfunction.
PMID- 28422054
TI - Growth Inhibition of Sulfate-Reducing Bacteria in Produced Water from the
Petroleum Industry Using Essential Oils.
AB - Strategies for the control of sulfate-reducing bacteria (SRB) in the oil industry
involve the use of high concentrations of biocides, but these may induce
bacterial resistance and/or be harmful to public health and the environment.
Essential oils (EO) produced by plants inhibit the growth of different
microorganisms and are a possible alternative for controlling SRB. We aimed to
characterize the bacterial community of produced water obtained from a Brazilian
petroleum facility using molecular methods, as well as to evaluate the
antimicrobial activity of EO from different plants and their major components
against Desulfovibrio alaskensis NCIMB 13491 and against SRB growth directly in
the produced water. Denaturing gradient gel electrophoresis revealed the presence
of the genera Pelobacter and Marinobacterium, Geotoga petraea, and the SRB
Desulfoplanes formicivorans in our produced water samples. Sequencing of dsrA
insert-containing clones confirmed the presence of sequences related to D.
formicivorans. EO obtained from Citrus aurantifolia, Lippia alba LA44 and
Cymbopogon citratus, as well as citral, linalool, eugenol and geraniol, greatly
inhibited (minimum inhibitory concentration (MIC) = 78 ug/mL) the growth of D.
alaskensis in a liquid medium. The same MIC was obtained directly in the produced
water with EO from L. alba LA44 (containing 82% citral) and with pure citral.
These findings may help to control detrimental bacteria in the oil industry.
PMID- 28422051
TI - Annexins as Overlooked Regulators of Membrane Trafficking in Plant Cells.
AB - Annexins are an evolutionary conserved superfamily of proteins able to bind
membrane phospholipids in a calcium-dependent manner. Their physiological roles
are still being intensively examined and it seems that, despite their general
structural similarity, individual proteins are specialized toward specific
functions. However, due to their general ability to coordinate membranes in a
calcium-sensitive fashion they are thought to participate in membrane flow. In
this review, we present a summary of the current understanding of cellular
transport in plant cells and consider the possible roles of annexins in different
stages of vesicular transport.
PMID- 28422055
TI - c-MYC-Making Liver Sick: Role of c-MYC in Hepatic Cell Function, Homeostasis and
Disease.
AB - Over 35 years ago, c-MYC, a highly pleiotropic transcription factor that
regulates hepatic cell function, was identified. In recent years, a considerable
increment in the number of publications has significantly shifted the way that
the c-MYC function is perceived. Overexpression of c-MYC alters a wide range of
roles including cell proliferation, growth, metabolism, DNA replication, cell
cycle progression, cell adhesion and differentiation. The purpose of this review
is to broaden the understanding of the general functions of c-MYC, to focus on c
MYC-driven pathogenesis in the liver, explain its mode of action under basal
conditions and during disease, and discuss efforts to target c-MYC as a plausible
therapy for liver disease.
PMID- 28422056
TI - Adiponectin and Intelectin-1: Important Adipokine Players in Obesity-Related
Colorectal Carcinogenesis.
AB - Overweight is believed to be associated with colorectal cancer risk. Adipose
tissue is loose connective tissue composed of adipocytes. It is now recognized as
a major endocrine organ, secreting humoral factors collectively called
adipokines. Aberrant hormonal systems consisting of modulated adipokines and
their receptors are thought to play a role in colorectal carcinogenesis and
cancer progression in obese conditions. However, it is still unclear whether and
how each adipokine relates to colorectal carcinogenesis. Notably, a couple of
molecules that were initially proposed to be obesity-related adipokines were
disqualified by subsequent studies. The adipokines, adiponectin, and intelectin-1
(also known as omentin-1), whose levels are decreased in obesity, act as tumor
suppressor factors in various cancers. Numerous studies have demonstrated a link
between the insufficient expression and function of adiponectin and its receptor,
T-cadherin, in colorectal carcinogenesis. Moreover, our recent study indicated
that loss of TMEM207, which is critical for the proper processing of intelectin-1
in the colon mucosa, leads to insufficient intelectin-1 production, thus
participating in colorectal carcinogenesis. Here, we discuss the recent
understanding of the role of adipokines in colorectal carcinogenesis and
subsequently describe the potent tumor suppressor roles of intelectin-1 and
TMEM207 in colorectal cancer.
PMID- 28422057
TI - Antifungal and Anti-Biofilm Activities of Acetone Lichen Extracts against Candida
albicans.
AB - Candida albicans is a commensal coloniser of the human gastrointestinal tract and
an opportunistic pathogen, especially thanks to its capacity to form biofilms.
This lifestyle is frequently involved in infections and increases the yeast
resistance to antimicrobials and immune defenses. In this context, 38 lichen
acetone extracts have been prepared and evaluated for their activity against C.
albicans planktonic and sessile cells. Minimum inhibitory concentrations of
extracts (MICs) were determined using the broth microdilution method. Anti
biofilm activity was evaluated using tetrazolium salt (XTT) assay as the ability
to inhibit the maturation phase (anti-maturation) or to eradicate a preformed 24
h old biofilm (anti-biofilm). While none of the extracts were active against
planktonic cells, biofilm maturation was limited by 11 of the tested extracts.
Seven extracts displayed both anti-maturation and anti-biofilm activities (half
maximal inhibitory concentrations IC50_mat and IC50_biof <= 100 ug/mL); Evernia
prunastri and Ramalina fastigiata were the most promising lichens (IC50_mat < 4
ug/mL and IC50_biof < 10 ug/mL). Chemical profiles of the active extracts
performed by thin layer chromatography (TLC) and high performance liquid
chromatography (HPLC) have been analyzed. Depsides, which were present in large
amounts in the most active extracts, could be involved in anti-biofilm
activities. This work confirmed that lichens represent a reservoir of compounds
with anti-biofilm potential.
PMID- 28422058
TI - Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases.
AB - Melatonin is a hormone synthesised and secreted by the pineal gland and other
organs. Its secretion, controlled by an endogenous circadian cycle, has been
proven to exert immunological, anti-oxidant, and anti-inflammatory effects that
can be beneficial in the treatment of certain dental diseases. This article is
aimed at carrying out a review of the literature published about the use of
melatonin in the dental field and summarising its potential effects. In this
review article, an extensive search in different databases of scientific journals
was performed with the objective of summarising all of the information published
on melatonin use in dental diseases, focussing on periodontal diseases and dental
implantology. Melatonin released in a natural way into the saliva, or added as an
external treatment, may have important implications for dental disorders, such as
periodontal disease, as well as in the osseointegration of dental implants, due
to its anti-inflammatory and osseoconductive effects. Melatonin has demonstrated
to have beneficial effects on dental pathologies, although further research is
needed to understand the exact mechanisms of this molecule.
PMID- 28422059
TI - Mismatch between Probiotic Benefits in Trials versus Food Products.
AB - Probiotic food products contain a variety of different bacterial strains and may
offer different health effects. The objective was to document the prevalence and
dosage of probiotic strains in the Canadian food supply and to review the
literature investigating these strains in order to understand what health
benefits these products may offer. The Food Label Information Program was used to
identify probiotic-containing products in the food supply. PubMed, Web of
Science, and Embase were searched for randomized controlled trials that tested
the health effects of these strains in humans. There were six probiotic
strains/strain combinations identified in the food supply. Thirty-one studies
investigated these strains and found that they are associated with decreased
diarrhea and constipation, improved digestive symptoms, glycemic control,
antioxidant status, blood lipids, oral health, and infant breastfeeding outcomes,
as well as enhanced immunity and support for Helicobacter pylori eradication.
There were a limited number of studies investigating these strains. Many studies
were funded by the food industry and tested dosages that were up to twenty-five
times the dosage found in most food products. Probiotic food products could have
health benefits not currently reported on their labels. However, many dosages are
too low to provide the benefits demonstrated in clinical trials. Further research
is needed to enable more effective use of these functional foods.
PMID- 28422061
TI - The Effect of Particles on Electrolytically Polymerized Thin Natural MCF Rubber
for Soft Sensors Installed in Artificial Skin.
AB - The aim of this study is to investigate the effect of particles as filler in soft
rubber sensors installed in artificial skin. We examine sensors made of natural
rubber (NR-latex) that include magnetic particles of Ni and Fe3O4 using magnetic
compound fluid (MCF). The 1-mm thickness of the electrolytically polymerized MCF
rubber makes production of comparatively thin rubber sensors feasible. We first
investigate the effect of magnetic particles Ni and Fe3O4 on the curing of MCF
rubber. Next, in order to adjust the electric properties of the MCF rubber, we
adopt Al2O3 dielectric particles. We investigate the effect of Al2O3 particles on
changes in electric current, voltage and temperature of electrolytically
polymerized MCF rubber liquid, and on the electric properties under the
application of normal and shear forces. By adjusting the ratio of Ni, Fe3O4,
Al2O3 and water in MCF rubber with Al2O3, it is possible to change the electric
properties.
PMID- 28422062
TI - Cross Layer Design for Optimizing Transmission Reliability, Energy Efficiency,
and Lifetime in Body Sensor Networks.
AB - High transmission reliability, energy efficiency, and long lifetime are pivotal
issues for wireless body area networks (WBANs. However, these performance metrics
are not independent of each other, making it hard to obtain overall improvements
through optimizing one single aspect. Therefore, a Cross Layer Design Optimal
(CLDO) scheme is proposed to simultaneously optimize transmission reliability,
energy efficiency, and lifetime of WBANs from several layers. Firstly, due to the
fact that the transmission power of nodes directly influences the reliability of
links, the optimized transmission power of different nodes is deduced, which is
able to maximize energy efficiency in theory under the premise that requirements
on delay and jitter are fulfilled. Secondly, a relay decision algorithm is
proposed to choose optimized relay nodes. Using this algorithm, nodes will choose
relay nodes that ensure a balance of network energy consumption, provided that
all nodes transmit with optimized transmission power and the same packet size.
Thirdly, the energy consumption of nodes is still unbalanced even with optimized
transmission power because of their different locations in the topology of the
network. In addition, packet size also has an impact on final performance
metrics. Therefore, a synthesized cross layer method for optimization is
proposed. With this method, the transmission power of nodes with more residual
energy will be enhanced while suitable packet size is determined for different
links in the network, leading to further improvements in the WBAN system. Both
our comprehensive theoretical analysis and experimental results indicate that the
performance of our proposed scheme is better than reported in previous studies.
Relative to the relay selection and power control game (RSPCG) scheme, the CLDO
scheme can enhance transmission reliability by more than 44.6% and prolong the
lifetime by as much as 33.2%.
PMID- 28422063
TI - Tellurite and Tellurate Reduction by the Aerobic Anoxygenic Phototroph
Erythromonas ursincola, Strain KR99 Is Carried out by a Novel Membrane Associated
Enzyme.
AB - Erythromonas ursincola, strain KR99 isolated from a freshwater thermal spring of
Kamchatka Island in Russia, resists and reduces very high levels of toxic
tellurite under aerobic conditions. Reduction is carried out by a constitutively
expressed membrane associated enzyme, which was purified and characterized. The
tellurite reductase has a molecular weight of 117 kDa, and is comprised of two
subunits (62 and 55 kDa) in a 1:1 ratio. Optimal activity occurs at pH 7.0 and 28
degrees C. Tellurite reduction has a Vmax of 5.15 umol/min/mg protein and a Km
of 3.36 mM. The enzyme can also reduce tellurate with a Vmax and Km of 1.08
umol/min/mg protein and 1.44 mM, respectively. This is the first purified
membrane associated Te oxyanion reductase.
PMID- 28422064
TI - Dried Plums, Prunes and Bone Health: A Comprehensive Review.
AB - The 2015-2020 Dietary Guidelines for Americans advocate for increasing fruit
intake and replacing energy-dense foods with those that are nutrient-dense.
Nutrition across the lifespan is pivotal for the healthy development and
maintenance of bone. The National Osteoporosis Foundation estimates that over
half of Americans age 50+ have either osteoporosis or low bone mass. Dried plums,
also commonly referred to as prunes, have a unique nutrient and dietary bioactive
profile and are suggested to exert beneficial effects on bone. To further
elucidate and summarize the potential mechanisms and effects of dried plums on
bone health, a comprehensive review of the scientific literature was conducted.
The PubMed database was searched through 24 January 2017 for all cell, animal,
population and clinical studies that examined the effects of dried plums and/or
extracts of the former on markers of bone health. Twenty-four studies were
included in the review and summarized in table form. The beneficial effects of
dried plums on bone health may be in part due to the variety of phenolics present
in the fruit. Animal and cell studies suggest that dried plums and/or their
extracts enhance bone formation and inhibit bone resorption through their actions
on cell signaling pathways that influence osteoblast and osteoclast
differentiation. These studies are consistent with clinical studies that show
that dried plums may exert beneficial effects on bone mineral density (BMD). Long
term prospective cohort studies using fractures and BMD as primary endpoints are
needed to confirm the effects of smaller clinical, animal and mechanistic
studies. Clinical and prospective cohort studies in men are also needed, since
they represent roughly 29% of fractures, and likewise, diverse race and ethnic
groups. No adverse effects were noted among any of the studies included in this
comprehensive review. While the data are not completely consistent, this review
suggests that postmenopausal women may safely consume dried plums as part of
their fruit intake recommendations given their potential to have protective
effects on bone loss.
PMID- 28422065
TI - Detection of (1,3)-beta-d-Glucan for the Diagnosis of Invasive Fungal Infection
in Liver Transplant Recipients.
AB - Invasive fungal infections (IFI) are complications after liver transplantation
involving high morbidity and mortality. (1,3)-beta-d-glucan (BG) is a biomarker
for IFI, but its utility remains uncertain. This study was designed to evaluate
the impact of BG following their diagnosis. Between January 2013 and May 2016,
271 liver transplants were performed in our institution. Serum samples were
tested for BG (Fungitell(r), Associates Cape Code Inc., Falmouth, MA, USA) at
least weekly between liver transplantation and the discharge of patients.
Nineteen patients (7%) were diagnosed with IFI, including 13 cases of invasive
candidiasis (IC), eight cases of invasive pulmonary aspergillosis, and one case
of septic arthritis due to Scedosporium apiospernum. Using a single BG sample for
the primary analysis of IFI, 95% (21/22) of the subjects had positive BG (>80
pg/mL) at the time of IFI diagnosis. The area under the ROC curves to predict IFI
was 0.78 (95% CI: 0.73-0.83). The sensitivity, specificity, positive predictive
value (PPV) and negative predictive value (NPV) of BG for IFI were 75% (95% CI:
65-83), 65% (62-68), 17% (13-21), and 96% (94-97), respectively. Based on their
high NPV, the BG test appears to constitute a good biomarker to rule out a
diagnosis of IFI.
PMID- 28422066
TI - Diabetogenic Effects of Ochratoxin A in Female Rats.
AB - In this study, the diabetogenic effects of long term Ochratoxin A (OTA)
administration in rats were investigated, and its role in the etiology of
diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these
purposes. The rats were divided into three different study and control groups
according to the duration of the OTA administration. The rats received 45 MUg OTA
daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups
were also used for the same time periods. Blood and pancreatic tissue samples
were collected during the necropsy at the end of the 6, 9 and 24 weeks. The
plasma values of insulin, glucagon and glucose were determined for the study and
control groups. Pancreatic lesions were evaluated via histopathological
examination and insulin and glucagon expression in these lesions was subsequently
determined using immunohistochemical methods. Statistically significant decreases
in insulin levels were observed, in contrast to increases in blood glucagon and
glucose levels. Histopathological examinations revealed slight to moderate
degeneration in Langerhans islet cells in all OTA-treated groups.
Immunohistochemistry of pancreatic tissue revealed decreased insulin and
increased glucagon expression. This study demonstrated that OTA may cause
pancreatic damage in the Langerhans islet and predispose rats to DM.
PMID- 28422060
TI - Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite
Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.
AB - Ghrelin is a hormone predominantly produced in and secreted from the stomach.
Ghrelin is involved in many physiological processes including feeding, the stress
response, and in modulating learning, memory and motivational processes. Ghrelin
does this by binding to its receptor, the growth hormone secretagogue receptor
(GHSR), a receptor found in relatively high concentrations in hypothalamic and
mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can
be explained by the effects of this hormone on regions of the brain that have a
more permeable blood brain barrier (BBB), ghrelin produced within the periphery
demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are
expressed. Therefore, one of the most pressing unanswered questions plaguing
ghrelin research is how GHSRs, distributed in brain regions protected by the BBB,
are activated despite ghrelin's predominant peripheral production and poor
ability to transverse the BBB. This manuscript will describe how peripheral
ghrelin activates central GHSRs to encourage feeding, and how central ghrelin
synthesis and ghrelin independent activation of GHSRs may also contribute to the
modulation of feeding behaviours.
PMID- 28422067
TI - Synthesis, Characterization, Antimicrobial and Antiproliferative Activity
Evaluation of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) Complexes with Isoniazid
Derived Compound.
AB - Hydrazone complexes of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) with N
isonicotinoyl-N'-(3-metoxy-2 hydroxybenzaldehyde)-hydrazone (HL) were synthesized
and characterized by different physico-chemical techniques including elemental
and thermal analysis, magnetic susceptibility measurements, molar electric
conductivity, as well as IR (infrared), 1H-NMR and 13C-NMR (hydrogen and carbon
nuclear magnetic resonance, UV-Vis (ultraviolet-visible), FAB (fast atom
bombardment), EPR (electron paramagnetic resonance), and mass spectroscopies. The
crystal structure of ligand was determined by single crystal X-ray diffraction
studies. Spectral data showed that hydrazone behaves as an ONO tridentate ligand
through the azomethine nitrogen, phenolate and keto oxygen atoms. For the
copper(II) complexes, metal-ligand bonding parameters were evaluated from the EPR
spectra. These parameters indicate the presence of in-plane pi bonding. In
addition, the f values of complexes 1-4 indicate small distortion from planarity.
The effect of these complexes on proliferation of human breast cancer (MCF-7 and
SKBR-3), human melanoma (A375), lung adenocarcinoma cells (NCI-H1573) and their
antibacterial activity against Escherichia coli, Klebsiella pneumoniae,
Staphylococcus aureus and Candida albicans strains were studied and compared with
those of free ligand. The ligand and complexes 1-3 showed significant
antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus
and Candida albicans in comparison to the control drugs. The complexes 2-4 could
be potential antitumor agents, leading to a significant improvement of the
cytotoxic activity when compared with HL.
PMID- 28422068
TI - A Low Cost Bluetooth Low Energy Transceiver for Wireless Sensor Network
Applications with a Front-end Receiver-Matching Network-Reusing Power Amplifier
Load Inductor.
AB - In this work, a low cost Bluetooth Low Energy (BLE) transceiver for wireless
sensor network (WSN) applications, with a receiver (RX)-matching network-reusing
power amplifier (PA) load inductor, is presented. In order to decrease the die
area, only two inductors were used in this work. Besides the one used in the
voltage control oscillator (VCO), the PA load inductor was reused as the RX
impedance matching component in the front-end. Proper controls have been applied
to achieve high transmitter (TX) input impedance when the transceiver is in the
receiving mode, and vice versa. This allows the TRX-switch/matching network
integration without significant performance degradation. The RX adopted a low-IF
structure and integrated a single-ended low noise amplifier (LNA), a current
bleeding mixer, a 4th complex filter and a delta-sigma continuous time (CT)
analog-to-digital converter (ADC). The TX employed a two-point PLL-based
architecture with a non-linear PA. The RX achieved a sensitivity of -93 dBm and
consumes 9.7 mW, while the TX achieved a 2.97% error vector magnitude (EVM) with
9.4 mW at 0 dBm output power. This design was fabricated in a 0.11 MUm
complementary metal oxide semiconductor (CMOS) technology and the front-end
circuit only occupies 0.24 mm2. The measurement results verify the effectiveness
and applicability of the proposed BLE transceiver for WSN applications.
PMID- 28422069
TI - Protein Stability and Unfolding Following Glycine Radical Formation.
AB - Glycine (Gly) residues are particularly susceptible to hydrogen abstraction;
which results in the formation of the capto-dative stabilized Calpha-centered Gly
radical (GLR) on the protein backbone. We examined the effect of GLR formation on
the structure of the Trp cage; tryptophan zipper; and the villin headpiece; three
fast-folding and stable miniproteins; using all-atom (OPLS-AA) molecular dynamics
simulations. Radicalization changes the conformation of the GLR residue and
affects both neighboring residues but did not affect the stability of the Trp
zipper. The stability of helices away from the radical center in villin were also
affected by radicalization; and GLR in place of Gly15 caused the Trp cage to
unfold within 1 us. These results provide new evidence on the destabilizing
effects of protein oxidation by reactive oxygen species.
PMID- 28422070
TI - One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon
Plasma Jet.
AB - Multiple evidence in animal models and in humans suggest a beneficial role of
cold physical plasma in wound treatment. Yet, risk assessment studies are
important to further foster therapeutic advancement and acceptance of cold plasma
in clinics. Accordingly, we investigated the longterm side effects of repetitive
plasma treatment over 14 consecutive days in a rodent full-thickness ear wound
model. Subsequently, animals were housed for 350 days and sacrificed thereafter.
In blood, systemic changes of the proinflammatory cytokines interleukin 1beta and
tumor necrosis factor alpha were absent. Similarly, tumor marker levels of alpha
fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the
expression levels of several cytokines and tumor markers in liver, lung, and skin
were found to be similar in the control and treatment group as well. Likewise,
histological and immunohistochemical analysis failed to detect abnormal
morphological changes and the presence of tumor markers such as carcinoembryonic
antigen, alpha-fetoprotein, or the neighbor of Punc11. Absence of neoplastic
lesions was confirmed by non-invasive imaging methods such as anatomical magnetic
resonance imaging and positron emission tomography-computed tomography. Our
results suggest that the beneficial effects of cold plasma in wound healing come
without apparent side effects including tumor formation or chronic inflammation.
PMID- 28422071
TI - Comparative Analysis of the Complete Chloroplast Genome of Four Endangered
Herbals of Notopterygium.
AB - Notopterygium H. de Boissieu (Apiaceae) is an endangered perennial herb endemic
to China. A good knowledge of phylogenetic evolution and population genomics is
conducive to the establishment of effective management and conservation
strategies of the genus Notopterygium. In this study, the complete chloroplast
(cp) genomes of four Notopterygium species (N. incisum C. C. Ting ex H. T. Chang,
N. oviforme R. H. Shan, N. franchetii H. de Boissieu and N. forrestii H. Wolff)
were assembled and characterized using next-generation sequencing. We
investigated the gene organization, order, size and repeat sequences of the cp
genome and constructed the phylogenetic relationships of Notopterygium species
based on the chloroplast DNA and nuclear internal transcribed spacer (ITS)
sequences. Comparative analysis of plastid genome showed that the cp DNA are the
standard double-stranded molecule, ranging from 157,462 bp (N. oviforme) to
159,607 bp (N. forrestii) in length. The circular DNA each contained a large
single-copy (LSC) region, a small single-copy (SSC) region, and a pair of
inverted repeats (IRs). The cp DNA of four species contained 85 protein-coding
genes, 37 transfer RNA (tRNA) genes and 8 ribosomal RNA (rRNA) genes,
respectively. We determined the marked conservation of gene content and sequence
evolutionary rate in the cp genome of four Notopterygium species. Three genes
(psaI, psbI and rpoA) were possibly under positive selection among the four
sampled species. Phylogenetic analysis showed that four Notopterygium species
formed a monophyletic clade with high bootstrap support. However, the
inconsistent interspecific relationships with the genus Notopterygium were
identified between the cp DNA and ITS markers. The incomplete lineage sorting,
convergence evolution or hybridization, gene infiltration and different sampling
strategies among species may have caused the incongruence between the nuclear and
cp DNA relationships. The present results suggested that Notopterygium species
may have experienced a complex evolutionary history and speciation process.
PMID- 28422072
TI - A Little Bug with a Big Bite: Impact of Hemlock Woolly Adelgid Infestations on
Forest Ecosystems in the Eastern USA and Potential Control Strategies.
AB - Hemlock woolly adelgid (Adelges tsugae Annand, HWA) remains the single greatest
threat to the health and sustainability of hemlock in the eastern USA. The loss
of hemlock trees leads to further negative impacts on the diversity and stability
of ecosystems in the eastern part of North America. It is, therefore, urgent to
develop effective control measures to reduce HWA populations and promote overall
hemlock health. Currently available individual and integrated approaches should
continue to be evaluated in the laboratory and in the field along with the
development of other new and innovative methods.
PMID- 28422074
TI - Recent Developments in Fiber Optics Humidity Sensors.
AB - A wide range of applications such as health, human comfort, agriculture, food
processing and storage, and electronic manufacturing, among others, require fast
and accurate measurement of humidity. Sensors based on optical fibers present
several advantages over electronic sensors and great research efforts have been
made in recent years in this field. The present paper reports the current trends
of optical fiber humidity sensors. The evolution of optical structures developed
towards humidity sensing, as well as the novel materials used for this purpose,
will be analyzed. Well-known optical structures, such as long-period fiber
gratings or fiber Bragg gratings, are still being studied towards an enhancement
of their sensitivity. Sensors based on lossy mode resonances constitute a
platform that combines high sensitivity with low complexity, both in terms of
their fabrication process and the equipment required. Novel structures, such as
resonators, are being studied in order to improve the resolution of humidity
sensors. Moreover, recent research on polymer optical fibers suggests that the
sensitivity of this kind of sensor has not yet reached its limit. Therefore,
there is still room for improvement in terms of sensitivity and resolution.
PMID- 28422075
TI - Multisensory System for the Detection and Localization of Peripheral Subcutaneous
Veins.
AB - This paper proposes a multisensory system for the detection and localization of
peripheral subcutaneous veins, as a first step for achieving automatic robotic
insertion of catheters in the near future. The multisensory system is based on
the combination of a SWIR (Short-Wave Infrared) camera, a TOF (Time-Of-Flight)
camera and a NIR (Near Infrared) lighting source. The associated algorithm
consists of two main parts: one devoted to the features extraction from the SWIR
image, and another envisaged for the registration of the range data provided by
the TOF camera, with the SWIR image and the results of the peripheral veins
detection. In this way, the detected subcutaneous veins are mapped onto the 3D
reconstructed surface, providing a full representation of the region of interest
for the automatic catheter insertion. Several experimental tests were carried out
in order to evaluate the capabilities of the presented approach. Preliminary
results demonstrate the feasibility of the proposed design and highlight the
potential benefits of the solution.
PMID- 28422073
TI - Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current
Status and Future Direction.
AB - A sustained and chronically-inflamed environment is characterized by the presence
of heterogeneous inflammatory cellular components, including neutrophils,
macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth
stimulating mediators (inflammatory cytokines and growth factors), chemotactic
factors (chemokines) and genotoxic substances (reactive oxygen species and
nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic
inflammation serves as an intrinsic niche for carcinogenesis and tumor
progression. In this article, we summarize the up-to-date findings regarding
definitive/possible causes and mechanisms of inflammation-related carcinogenesis
derived from experimental and clinical studies. We also propose 10 strategies, as
well as candidate agents for the prevention of inflammation-related
carcinogenesis.
PMID- 28422076
TI - ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using
Zebrafish.
AB - Toxicity is one of the major attrition causes during the drug development
process. In that line, cardio-, neuro-, and hepatotoxicities are among the main
reasons behind the retirement of drugs in clinical phases and post market
withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming
an important tool to assess the toxicity and efficacy of novel drugs. This animal
model has, from early developmental stages, fully functional organs from a
physiological point of view. Thus, drug-induced organ-toxicity can be detected in
larval stages, allowing a high predictive power on possible human drug-induced
liabilities. Hence, zebrafish can bridge the gap between preclinical in vitro
safety assays and rodent models in a fast and cost-effective manner. ZeGlobalTox
is an innovative assay that sequentially integrates in vivo cardio-, neuro-, and
hepatotoxicity assessment in the same animal, thus impacting strongly in the 3Rs
principles. It Reduces, by up to a third, the number of animals required to
assess toxicity in those organs. It Refines the drug toxicity evaluation through
novel physiological parameters. Finally, it might allow the Replacement of
classical species, such as rodents and larger mammals, thanks to its high
predictivity (Specificity: 89%, Sensitivity: 68% and Accuracy: 78%).
PMID- 28422077
TI - Economic Burden of Obesity: A Systematic Literature Review.
AB - Background: The rising prevalence of obesity represents an important public
health issue. An assessment of its costs may be useful in providing
recommendations for policy and decision makers. This systematic review aimed to
assess the economic burden of obesity and to identify, measure and describe the
different obesity-related diseases included in the selected studies. Methods: A
systematic literature search of studies in the English language was carried out
in Medline (PubMed) and Web of Science databases to select cost-of-illness
studies calculating the cost of obesity in a study population aged >=18 years
with obesity, as defined by a body mass index of >=30 kg/m2, for the whole
selected country. The time frame for the analysis was January 2011 to September
2016. Results: The included twenty three studies reported a substantial economic
burden of obesity in both developed and developing countries. There was
considerable heterogeneity in methodological approaches, target populations,
study time frames, and perspectives. This prevents an informative comparison
between most of the studies. Specifically, there was great variety in the
included obesity-related diseases and complications among the studies.
Conclusions: There is an urgent need for public health measures to prevent
obesity in order to save societal resources. Moreover, international consensus is
required on standardized methods to calculate the cost of obesity to improve
homogeneity and comparability. This aspect should also be considered when
including obesity-related diseases.
PMID- 28422078
TI - Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming.
AB - Antivenom therapy is currently the standard practice for treating neuromuscular
dysfunction in snake envenoming. We reviewed the clinical and experimental
evidence-base for the efficacy and effectiveness of antivenom in snakebite
neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction,
and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging
the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the
nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for
neurotoxicity include rodent lethality tests, which are problematic, and in vitro
pharmacological tests such as nerve-muscle preparation studies, that appear to
provide more clinically meaningful information. We searched MEDLINE (from 1946)
and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded
no randomised placebo-controlled trials of antivenom for neuromuscular
dysfunction. There were several randomised and non-randomised comparative trials
that compared two or more doses of the same or different antivenom, and numerous
cohort studies and case reports. The majority of studies available had
deficiencies including poor case definition, poor study design, small sample size
or no objective measures of paralysis. A number of studies demonstrated the
efficacy of antivenom in human envenoming by clearing circulating venom. Studies
of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.)
and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established
neurotoxicity, but early administration may be associated with decreased severity
or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic
neurotoxins, including some cobra species (Naja spp.), provide preliminary
evidence that neurotoxicity may be reversed with antivenom, but placebo
controlled studies with objective outcome measures are required to confirm this.
PMID- 28422080
TI - Study on Temperature and Synthetic Compensation of Piezo-Resistive Differential
Pressure Sensors by Coupled Simulated Annealing and Simplex Optimized Kernel
Extreme Learning Machine.
AB - As a high performance-cost ratio solution for differential pressure measurement,
piezo-resistive differential pressure sensors are widely used in engineering
processes. However, their performance is severely affected by the environmental
temperature and the static pressure applied to them. In order to modify the non
linear measuring characteristics of the piezo-resistive differential pressure
sensor, compensation actions should synthetically consider these two aspects.
Advantages such as nonlinear approximation capability, highly desirable
generalization ability and computational efficiency make the kernel extreme
learning machine (KELM) a practical approach for this critical task. Since the
KELM model is intrinsically sensitive to the regularization parameter and the
kernel parameter, a searching scheme combining the coupled simulated annealing
(CSA) algorithm and the Nelder-Mead simplex algorithm is adopted to find an
optimal KLEM parameter set. A calibration experiment at different working
pressure levels was conducted within the temperature range to assess the proposed
method. In comparison with other compensation models such as the back-propagation
neural network (BP), radius basis neural network (RBF), particle swarm
optimization optimized support vector machine (PSO-SVM), particle swarm
optimization optimized least squares support vector machine (PSO-LSSVM) and
extreme learning machine (ELM), the compensation results show that the presented
compensation algorithm exhibits a more satisfactory performance with respect to
temperature compensation and synthetic compensation problems.
PMID- 28422079
TI - Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates
Endothelial Transient Receptor Potential Vanilloid-Type 1.
AB - The natural product, rutaecarpine (RUT), is the main effective component of
Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has
vasodilation, anticoagulation, and anti-inflammatory activities. However, further
therapeutic applications are limited by its cytotoxicity. Thus, a derivative of
RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that
showed no cytotoxicity toward RAW264.7 macrophages at 20 MUM. In an anti
inflammation experiment, it inhibited the production of nitric oxide (NO) and
tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated RAW264.7
macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by
LPS were also downregulated. After 24 h of treatment, F-RUT significantly
inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT
promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and
endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced
the inflammation in ovalbumin/alum-challenged mice. These results suggest that
the novel synthetic F-RUT exerts activities against inflammation and
vasodilation, while displaying less toxicity than its lead compound.
PMID- 28422081
TI - Non-Responsive Feeding Practices, Unhealthy Eating Behaviors, and Risk of Child
Overweight and Obesity in Southeast Asia: A Systematic Review.
AB - Childhood obesity is increasing dramatically in many Southeast Asian countries,
and becoming a significant public health concern. This review summarizes the
evidence on associations between parental feeding practices, child eating
behaviors, and the risk of overweight and obesity in Southeast Asian children 2
12 years old. We systematically searched five electronic academic/research
(PubMed, PsycINFO, ProQuest Nursing, Medline, and CINAHL) databases using the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
statement for peer-reviewed studies published in English between January 2000 and
December 2016. Fourteen observational studies met the inclusion criteria and were
reviewed. Reviewed studies were examined separately for preschool- and school
aged children and revealed that non-responsive parental feeding practices and
unhealthy child eating behaviors were associated with a risk of child overweight
and obesity in several Southeast Asian countries. Nonetheless, due to the small
number of identified studies (n = 14) and because only about half of the
Southeast Asian countries (Thailand, Vietnam, Singapore, the Philippines, and
Malaysia) were represented (5/11) in the examined studies, additional research is
needed to further understand the factors associated with childhood obesity among
children in Southeast Asia to develop interventions that are tailored to the
specific needs of Southeast Asian countries and designed to address practices and
behaviors that may promote childhood obesity.
PMID- 28422083
TI - Nasopharyngeal Carriage and Antimicrobial Susceptibility Patterns of
Streptococcus pneumoniae among Children under Five in Southwest Ethiopia.
AB - Nasopharyngeal carriage of Streptococcus pneumoniae is found to play an important
role in the development and transmission of pneumococcal diseases. In this study,
we assessed the nasopharyngeal carriage, antimicrobial susceptibility patterns
and associated risk factors of S. pneumoniae among children under five. A total
of 361 children under five attending the outpatient department of Shanan Gibe
Hospital in Jimma, Southwest Ethiopia were enrolled from June to September 2014.
Nasopharyngeal specimens were collected using sterile plastic applicator rayon
tipped swab and inoculated on tryptone soy agar supplemented with 5% sheep blood
and 5 ug/mL gentamycin. Antimicrobial susceptibility testing was performed using
the modified disk diffusion method. The overall prevalence of S. pneumoniae
carriage was 43.8% (158/361) among children under five. Resistance to
tetracycline, cotrimoxazole, penicillin, chloramphenicol and erythromycin was
observed in 53.2% (84/158), 43.7% (69/158), 36.1% (57/158), 13.3% (21/158) and
8.9% (14/158) of isolates respectively. Multidrug resistance was seen in 17.7%
(28/158) of isolates. In multivariate logistic regression analysis, children
living with sibling(s) < 5 years old (adjusted odds ratio (AOR) = 1.798; 95%
confidence interval (CI), 1.169-2.766) and malnutrition (AOR = 2.065; 95% CI,
1.239-3.443) were significantly associated with S. pneumoniae carriage. A high
nasopharyngeal carriage of S. pneumoniae was observed among children under five
in Southwest Ethiopia. There should be a strategy to prevent S. pneumoniae
nasopharyngeal colonization and identify the appropriate antibiotic to the
individual child.
PMID- 28422082
TI - Molecular Imprinting of Macromolecules for Sensor Applications.
AB - Molecular recognition has an important role in numerous living systems. One of
the most important molecular recognition methods is molecular imprinting, which
allows host compounds to recognize and detect several molecules rapidly,
sensitively and selectively. Compared to natural systems, molecular imprinting
methods have some important features such as low cost, robustness, high
recognition ability and long term durability which allows molecularly imprinted
polymers to be used in various biotechnological applications, such as
chromatography, drug delivery, nanotechnology, and sensor technology. Sensors are
important tools because of their ability to figure out a potentially large number
of analytical difficulties in various areas with different macromolecular
targets. Proteins, enzymes, nucleic acids, antibodies, viruses and cells are
defined as macromolecules that have wide range of functions are very important.
Thus, macromolecules detection has gained great attention in concerning the
improvement in most of the studies. The applications of macromolecule imprinted
sensors will have a spacious exploration according to the low cost, high
specificity and stability. In this review, macromolecules for molecularly
imprinted sensor applications are structured according to the definition of
molecular imprinting methods, developments in macromolecular imprinting methods,
macromolecular imprinted sensors, and conclusions and future perspectives. This
chapter follows the latter strategies and focuses on the applications of
macromolecular imprinted sensors. This allows discussion on how sensor strategy
is brought to solve the macromolecules imprinting.
PMID- 28422084
TI - An Algorithm for Timely Transmission of Solicitation Messages in RPL for Energy
Efficient Node Mobility.
AB - The IPv6 Routing Protocol for Low Power and Lossy Networks (RPL) was proposed for
various applications of IPv6 low power wireless networks. While RPL supports
various routing metrics and is designed to be suitable for wireless sensor
network environments, it does not consider the mobility of nodes. Therefore,
there is a need for a method that is energy efficient and that provides stable
and reliable data transmission by considering the mobility of nodes in RPL
networks. This paper proposes an algorithm to support node mobility in RPL in an
energy-efficient manner and describes its operating principle based on different
scenarios. The proposed algorithm supports the mobility of nodes by dynamically
adjusting the transmission interval of the messages that request the route based
on the speed and direction of the motion of mobile nodes, as well as the costs
between neighboring nodes. The performance of the proposed algorithm and previous
algorithms for supporting node mobility were examined experimentally. From the
experiment, it was observed that the proposed algorithm requires fewer messages
per unit time for selecting a new parent node following the movement of a mobile
node. Since fewer messages are used to select a parent node, the energy
consumption is also less than that of previous algorithms.
PMID- 28422085
TI - Resonant Rectifier ICs for Piezoelectric Energy Harvesting Using Low-Voltage Drop
Diode Equivalents.
AB - Herein, we present the design technique of a resonant rectifier for piezoelectric
(PE) energy harvesting. We propose two diode equivalents to reduce the voltage
drop in the rectifier operation, a minuscule-drop-diode equivalent (MDDE) and a
low-drop-diode equivalent (LDDE). The diode equivalents are embedded in resonant
rectifier integrated circuits (ICs), which use symmetric bias-flip to reduce the
power used for charging and discharging the internal capacitance of a PE
transducer. The self-startup function is supported by synchronously generating
control pulses for the bias-flip from the PE transducer. Two resonant rectifier
ICs, using both MDDE and LDDE, are fabricated in a 0.18 MUm CMOS process and
their performances are characterized under external and self-power conditions.
Under the external-power condition, the rectifier using LDDE delivers an output
power POUT of 564 MUW and a rectifier output voltage VRECT of 3.36 V with a power
transfer efficiency of 68.1%. Under self-power conditions, the rectifier using
MDDE delivers a POUT of 288 MUW and a VRECT of 2.4 V with a corresponding
efficiency of 78.4%. Using the proposed bias-flip technique, the power extraction
capability of the proposed rectifier is 5.9 and 3.0 times higher than that of a
conventional full-bridge rectifier.
PMID- 28422086
TI - Association Between Secretoglobin Family 3A Member 2 (SCGB3A2) Gene Polymorphisms
and Asthma in a Korean Population.
AB - BACKGROUND Secretoglobin family 3A member 2 (SCGB3A2) plays an important role in
secreting lung surfactant protein, which is a downstream target of thyroid
transcription factor. MATERIAL AND METHODS We investigated whether single
nucleotide polymorphisms (SNPs) of SCGB3A2 gene contribute to susceptibility to
asthma. To explore this possible association, 2 promoter SNPs (rs6882292, 659 G/A
and rs1368408, -112 G/A) and missense SNP (rs151333009, stop codon) were tested
in SCGB3A2 gene in 101 asthma patients and 377 healthy control subjects. SNPStats
was used to obtain odds ratio (OR), 95% confidence intervals (CI), and P value
adjusted for age and sex as covariables. Logistic regression method in each model
(dominant, recessive, and log-additive) was applied to analyze genetic data.
RESULTS rs151333009 SNP showed a monomorphic genotype. Two promoter SNPs
(rs6882292, -659 G/A and rs1368408, -112 G/A) showed significant association with
asthma (rs6882292, OR=2.66, 95% CI=1.42-5.01, p=0.0033 in dominant model,
OR=2.45, 95% CI=1.33-4.54, p=0.0055 in log-additive model; rs1368408, OR=1.59,
95% CI=1.02-2.49, p=0.041 in dominant model, OR=3.02, 95% CI=1.15-7.90, p=0.03 in
recessive model, OR=1.63, 95% CI=1.63, 95% CI=1.12-2.37, p=0.012 in log-additive
model). CONCLUSIONS These results suggest that the promoter SNPs (rs6882292 and
rs1368408) of SCGB3A2 gene may contribute to susceptibility to asthma in a Korean
population.
PMID- 28422087
TI - Clinical comparison of patient outcomes following implantation of trifocal or
bifocal intraocular lenses: a systematic review and meta-analysis.
AB - To assess the visual effects of trifocal intraocular lenses (IOLs) compared to
bifocal IOLs in cataract surgery, a meta-analysis of prospective comparative
clinical trials (including 4 randomized controlled trials and 4 cohorts) was
conducted. The defocus curves showed a better distance-corrected intermediate
visual acuity (VA) for the trifocal group (MD -0.07; 95% CI, -0.10 to -0.05; p <
0.00001), while the VA outcomes showed no significant difference in distance VA
(MD -0.03; 95% CI, -0.06 to 0.01; p = 0.13 for uncorrected distance VA and MD
0.00; 95% CI, -0.01 to 0.01; p = 0.78 for distance-corrected distance VA), near
VA (MD -0.01; 95% CI, -0.07 to 0.04; p = 0.68 for uncorrected near VA and MD
0.01; 95% CI, -0.06 to 0.04; p = 0.66 for distance-corrected near VA) or
refraction between the two groups. Contrast sensitivity and subjective visual
quality yielded less conclusive results. Overall, a patient may achieve better
intermediate VA with a trifocal IOL than with a bifocal IOL without any adverse
effect on distance or near VA. The findings on contrast sensitivity and
subjective visual quality were heterogeneous, with no clear results favoring
either option.
PMID- 28422088
TI - Clustering by fast search and merge of local density peaks for gene expression
microarray data.
AB - Clustering is an unsupervised approach to classify elements based on their
similarity, and it is used to find the intrinsic patterns of data. There are
enormous applications of clustering in bioinformatics, pattern recognition, and
astronomy. This paper presents a clustering approach based on the idea that
density wise single or multiple connected regions make a cluster, in which
density maxima point represents the center of the corresponding density region.
More precisely, our approach firstly finds the local density regions and
subsequently merges the density connected regions to form the meaningful
clusters. This idea empowers the clustering procedure, in which outliers are
automatically detected, higher dense regions are intuitively determined and
merged to form clusters of arbitrary shape, and clusters are identified
regardless the dimensionality of space in which they are embedded. Extensive
experiments are performed on several complex data sets to analyze and compare our
approach with the state-of-the-art clustering methods. In addition, we
benchmarked the algorithm on gene expression microarray data sets for cancer
subtyping; to distinguish normal tissues from tumor; and to classify multiple
tissue data sets.
PMID- 28422090
TI - Surgical treatment in Paget's disease with invasive ductal carcinoma: an
observational study based on SEER.
AB - The aim is to analyse the clinical presentation, treatment and outcomes in
patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with
special emphasis on the role of surgical treatment. Using data obtained by the
Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we
investigated the differences in characteristics, overall survival (OS), and
breast cancer-specific mortality (BCSM) between patients with PD-IDC and those
with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD
IDC had a better prognosis and lower mortality in adjusted analyses. In the
multivariate analysis of cases with PD-IDC, history of ALND was significantly
associated with OS while Her2 status were associated with BCSM. Further, subgroup
analysis demonstrated no difference between surgical treatment subgroups for
either OS or BCSM. The results demonstrated that PD-IDC appears to alter the
association between prognosis and Her2 status. Meanwhile, breast-conserving
surgery with radiotherapy may be a feasible treatment alternative and sentinel
lymph node biopsy should be considered as an appropriate treatment for patients
with PD-IDC.
PMID- 28422089
TI - Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport.
AB - Brown and beige adipocytes combust nutrients for thermogenesis and through their
metabolic activity decrease pro-atherogenic remnant lipoproteins in
hyperlipidemic mice. However, whether the activation of thermogenic adipocytes
affects the metabolism and anti-atherogenic properties of high-density
lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in
response to pharmacological stimulation of thermogenesis linked to increased HDL
levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological
thermogenic activation enhances HDL remodelling, which is associated with
specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic
stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces
reverse cholesterol transport in mice. Mechanistically, we show that
intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL
by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in
liver. Our findings corroborate the notion that high metabolic activity of
thermogenic adipocytes confers atheroprotective properties via increased systemic
cholesterol flux through the HDL compartment.
PMID- 28422091
TI - Male African elephants discriminate and prefer vocalizations of unfamiliar
females.
AB - Gaining information about conspecifics via long-distance vocalizations is crucial
for social and spatially flexible species such as the African elephant (Loxodonta
africana). Female elephants are known to discriminate individuals and kin based
on acoustic cues. Specifically, females approached the loudspeaker exclusively
with playbacks of familiar individuals with high association indexes,
intentionally fusing with their affiliates. For males, which are less bonded,
gathering social information via vocalizations could still have important
implications, but little is known about their vocal discrimination skills. We
experimentally tested the ability of male African elephants to discriminate the
social rumbles of familiar (from the same population) versus unfamiliar females.
Male elephants discriminated and preferentially moved towards the rumbles of
unfamiliar females, showing longer attentive reactions and significantly more
orientating (facing and approaching the speaker) behavior. The increased
orientating response of males towards playbacks of unfamiliar females is converse
to the reaction of female subjects. Our results provide evidence that male
elephants extract social information from vocalizations, yet with a different
intention than females. Accordingly, males might use social cues in vocalizations
to assess mating opportunities, which may involve selection to identify
individuals or kin in order to avoid inbreeding.
PMID- 28422093
TI - Quantum Enhanced Inference in Markov Logic Networks.
AB - Markov logic networks (MLNs) reconcile two opposing schools in machine learning
and artificial intelligence: causal networks, which account for uncertainty
extremely well, and first-order logic, which allows for formal deduction. An MLN
is essentially a first-order logic template to generate Markov networks.
Inference in MLNs is probabilistic and it is often performed by approximate
methods such as Markov chain Monte Carlo (MCMC) Gibbs sampling. An MLN has many
regular, symmetric structures that can be exploited at both first-order level and
in the generated Markov network. We analyze the graph structures that are
produced by various lifting methods and investigate the extent to which quantum
protocols can be used to speed up Gibbs sampling with state preparation and
measurement schemes. We review different such approaches, discuss their
advantages, theoretical limitations, and their appeal to implementations. We find
that a straightforward application of a recent result yields exponential speedup
compared to classical heuristics in approximate probabilistic inference, thereby
demonstrating another example where advanced quantum resources can potentially
prove useful in machine learning.
PMID- 28422092
TI - Hierarchical assembly of centriole subdistal appendages via centrosome binding
proteins CCDC120 and CCDC68.
AB - In animal cells, the centrosome is the main microtubule-organizing centre where
microtubules are nucleated and anchored. The centriole subdistal appendages
(SDAs) are the key structures that anchor microtubules in interphase cells, but
the composition and assembly mechanisms of SDAs are not well understood. Here, we
reveal that centrosome-binding proteins, coiled-coil domain containing (CCDC) 120
and CCDC68 are two novel SDA components required for hierarchical SDA assembly in
human cells. CCDC120 is anchored to SDAs by ODF2 and recruits CEP170 and Ninein
to the centrosome through different coiled-coil domains at its N terminus. CCDC68
is a CEP170-interacting protein that competes with CCDC120 in recruiting CEP170
to SDAs. Furthermore, CCDC120 and CCDC68 are required for centrosome microtubule
anchoring. Our findings elucidate the molecular basis for centriole SDA
hierarchical assembly and microtubule anchoring in human interphase cells.
PMID- 28422094
TI - Erratum: Nonlinear detection of secondary isotopic chemical shifts in NMR through
spin noise.
PMID- 28422095
TI - Structure and Variability of the North Equatorial Current/Undercurrent from
Mooring Measurements at 130 degrees E in the Western Pacific.
AB - The mean structure and variability of the North Equatorial Current/Undercurrent
(NEC/NEUC) are investigated with one-year Acoustic Doppler Current Profilers
measurements from 4 subsurface moorings deployed at 10.5 degrees N, 13 degrees N,
15.5 degrees N, and 18 degrees N along 130 degrees E in the western Pacific. The
strong westward flowing NEC ranges from the sea surface down to 400 m, and the
mean zonal velocity of the NEC at 10.5 degrees N is around -30 cm/s at the depth
of 70 m. Eastward flowing NEUC jets are detected below the NEC at 10.5 degrees N
and 13 degrees N, and the depth of the NEUC could reach at least 900 m. The mean
velocity of the NEUC is around 4.2 cm/s at 800 m. No eastward undercurrents are
observed at 15 degrees N and 18 degrees N. The mooring measurements also reveal a
strong intraseasonal variability of the currents at all 4 mooring sites, and the
period is around 70-120 days. The vertical structure of this intraseasonal
variability varies at different latitudes. The variability of the NEUC jets at
10.5 degrees N and 13 degrees N appears to be dominated by subthermocline
signals, while the variability of the currents at 15.5 degrees N and 18 degrees N
is dominated by surface-intensified signals.
PMID- 28422096
TI - Response to Protocol Review Scenario: Teamwork can go a long way.
PMID- 28422097
TI - Design, analysis and reporting of tumor models.
PMID- 28422098
TI - Treating mouse tumors with microglia.
PMID- 28422099
TI - Characterizing the zebrafish synaptic proteome.
PMID- 28422100
TI - Response to Protocol Review Scenario: Before the amendment.
PMID- 28422101
TI - Response to Protocol Review Scenario: More work upfront to avoid last minute
problems.
PMID- 28422102
TI - Shaping up two-photon imaging in vivo.
PMID- 28422103
TI - C. elegans takes out the trash.
PMID- 28422104
TI - Cas9 cuts to the quick in the cortex.
PMID- 28422105
TI - What role should an IACUC play when a PI's manuscript is on the line?
PMID- 28422106
TI - Mouse models move to Asian markets.
PMID- 28422110
TI - Maximizing survival: lung protective ventilation.
PMID- 28422111
TI - Training mouse pathologists: 15 years of workshops on the pathology of mouse
models of human disease.
PMID- 28422112
TI - Accurate and effective multidrug-resistant Mycobacterium tuberculosis detection
method using gap-filling ligation coupled with high-resolution capillary
electrophoresis-based single strand conformation polymorphism.
AB - Tuberculosis (TB) has severely threatened public health via emerging multidrug
resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis
(MTB) strains. For effective TB treatment, rapid, accurate, and multiplex
detection of drug resistance is extremely important. However, conventional
methods for TB diagnosis are time consuming and have a limited effect on
treatment. Nucleic acid-based molecular detection methods have been developed as
an effective MDR/XDR-TB diagnosis technology. Among the nucleic acid-based
methods, ligation-dependent methods are attractive as MDR/XDR-MTB detection
technologies, but multiplex analysis is limited by the detection method. Although
an electrophoresis-based method is considered for multiple target detection
because it is free from the errors pertaining to hybridization-based systems, the
procedure of multiplex analysis is quite complicated owing to the DNA size-based
separation system. In this study, we report an accurate, rapid, and simple
multiple MDR/XDR-MTB detection technology using gap-filling ligation reaction
coupled with high-resolution capillary electrophoresis-based single-strand
conformation polymorphism. Using this system, rapid and accurate MDR/XDR-MTB
detection is feasible via similar length probes without the complicated step of
probe design. We found that this method could accurately and effectively detect
highly polymorphic regions in specific codons associated with drug resistance.
PMID- 28422113
TI - Increased spontaneous MEG signal diversity for psychoactive doses of ketamine,
LSD and psilocybin.
AB - What is the level of consciousness of the psychedelic state? Empirically,
measures of neural signal diversity such as entropy and Lempel-Ziv (LZ)
complexity score higher for wakeful rest than for states with lower conscious
level like propofol-induced anesthesia. Here we compute these measures for
spontaneous magnetoencephalographic (MEG) signals from humans during altered
states of consciousness induced by three psychedelic substances: psilocybin,
ketamine and LSD. For all three, we find reliably higher spontaneous signal
diversity, even when controlling for spectral changes. This increase is most
pronounced for the single-channel LZ complexity measure, and hence for temporal,
as opposed to spatial, signal diversity. We also uncover selective correlations
between changes in signal diversity and phenomenological reports of the intensity
of psychedelic experience. This is the first time that these measures have been
applied to the psychedelic state and, crucially, that they have yielded values
exceeding those of normal waking consciousness. These findings suggest that the
sustained occurrence of psychedelic phenomenology constitutes an elevated level
of consciousness - as measured by neural signal diversity.
PMID- 28422114
TI - Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose
homeostasis.
PMID- 28422115
TI - Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose
homeostasis.
PMID- 28422116
TI - Skin Cancer: Have melanoma and skin cancer finally met their match?
PMID- 28422117
TI - Ultrahigh Responsivity and Detectivity Graphene-Perovskite Hybrid
Phototransistors by Sequential Vapor Deposition.
AB - In this work, graphene-methylammonium lead iodide (MAPbI3) perovskite hybrid
phototransistors fabricated by sequential vapor deposition are demonstrated.
Ultrahigh responsivity of 1.73 * 107 A W-1 and detectivity of 2 * 1015 Jones are
achieved, with extremely high effective quantum efficiencies of about 108% in the
visible range (450-700 nm). This excellent performance is attributed to the ultra
flat perovskite films grown by vapor deposition on the graphene sheets. The
hybrid structure of graphene covered with uniform perovskite has high exciton
separation ability under light exposure, and thus efficiently generates
photocurrents. This paper presents photoluminescence (PL) images along with
statistical analysis used to study the photo-induced exciton behavior. Both
uniform and dramatic PL intensity quenching has been observed over entire
measured regions, consistently demonstrating excellent exciton separation in the
devices.
PMID- 28422118
TI - Nutrient regulation of beta-cell function: what do islet cell/animal studies tell
us?
AB - Diabetes mellitus is widely recognised as one of the most serious metabolic
diseases worldwide, and its incidence in Asian countries is growing at an
alarming rate. Type 2 diabetes (T2DM) is closely associated with age, sedentary
lifestyle and poor diet. In T2DM, beta-cell dysfunction will occur before
hyperglycaemia develops. Excessive levels of glucose, lipid and various
inflammatory factors interact at the level of the pancreatic islet to promote
beta-cell dysfunction. Pancreatic beta-cell lines have been widely utilised since
the early 1980s and have contributed a large volume of important information
regarding molecular, metabolic and genetic mechanisms that regulate insulin
secretion. The purpose of this review is to describe the origin and
characteristics of the most commonly used beta-cell lines and their contribution
to discovery of fundamental regulatory processes that control insulin production
and release. Pancreatic islets obtained from rodents as well as other animals
have additionally provided information on the architecture and three-dimensional
design of this endocrine tissue that allows precise regulation of hormone
release. Understanding the nature of failure of physiologic and metabolic
processes leading to insufficient insulin release and subsequent diabetes has
allowed development of novel anti-diabetic therapeutics, now in common use,
worldwide.
PMID- 28422120
TI - Trends of increases in potential risk factors and prevalence rates of diabetes
mellitus in Thailand.
AB - Over the past three decades, undernutrition in Thailand has drastically reduced
by over seven times. However, since 1995 the number of patients afflicted with
non-communicable diseases, such as diabetes mellitus, has rapidly increased, even
among the young. Unhealthy life styles due to urbanization are a major reason for
this increase. Less physical activity and low consumption of fruits and
vegetables, as well as high consumption of added free sugar, are common. Every
year, the Thai people increase their consumption of energy from fat and protein,
while lowering their intake of energy from complex carbohydrates. Per capita and
on average, a Thai individual consumes up to 20% of total energy from added free
sugar. Barker's hypothesis and Developmental Origins of Health and Disease
hypothesis (DOHaD) can partially explain the increase in diabetes mellitus at
this rapid rate. To alleviate the problem, the main strategy has been consumer
education to reduce diabetes mellitus prevalence. Sugar elimination from infant
formula is mandatory and sugar taxation is being considered. Simplified nutrition
labeling is voluntarily as part of consumer education, as well as encouraging
food industries to produce healthier food products. Currently, a multi-sectoral
approach is used for alleviating diabetes mellitus in Thailand.
PMID- 28422119
TI - Current lifestyle factors that increase risk of T2DM in China.
AB - The Report on the Status of Nutrition and Chronic Diseases of Chinese residents
(2015) indicated that the prevalence of diabetes was 9.7% among adults aged ?18
years, which markedly increased from 2.6% in 2002 within 10 years. In addition to
the social economic factors, transitions in food consumption, behavioral and
lifestyle playing the important roles in the fast increase of type 2 diabetes
mellitus (T2DM). In 2010-2012, the cereal food consumption of Chinese residents
was 337 g/d, vegetables consumption 269 g/d, fruit consumption 41 g/d, legume and
legume products 11 g/d, dairy and dairy products consumption 25 g/d, meat
consumption 90 g/d, edible oil consumption 42 g/d and dietary fiber 10.8 g/d. The
traditional Chinese dietary pattern (high consumption of rice, pork and
vegetables) is shifting towards a dietary pattern with high consumption of meats
and edible oil but low consumption of cereals and vegetables. Smoking, breakfast
omitting and high consumption of sugar-sweetened beverages became popular.
Insufficient physical activity rate was 31.7%. Less sleep duration and poorer
sleep quality was also common for Chinese residents. Concerning early life
factors, residents exposed to the Chinese famine (1959-1961) during fetal life
and childhood had an increased risk of hyperglycemia. As a conclusion, current
unhealthy lifestyle has inversely effect on the incidence and development of
T2DM, especially for the increased intake of fat and carbohydrate, the transition
of dietary pattern, the extension of sedentary time and the increasing rate of
obesity. Lifestyle management should be taken seriously as a part of diabetes
prevention.
PMID- 28422121
TI - A decrease in blood cholesterol after gastrostomy could impact survival in ALS.
AB - Although the global benefits of gastrostomy have been proven in amyotrophic
lateral sclerosis (ALS), the impact on biological parameters has not been
explored yet. The aim of this preliminary work was to evaluate the modification
of biological parameters in patients with ALS undergoing gastrostomy. We
retrospectively collected clinical and biological data from 44 patients having
undergone gastrostomy at three time points (T0, T1 and T2: before, at the time of
and after gastrostomy). We examined the relationship between the biological
parameters and disease progression. Variations of the concentrations of total
cholesterol significantly differed before (T1-T0) vs those after gastrostomy (T2
T1; P=0.0044). The variations of total cholesterol and low-density lipoprotein
cholesterol concentrations after gastrostomy were negatively associated with
survival (P=0.0002). This study showed for the first time that patients with ALS
fed quite exclusively by gastrostomy had decreased blood cholesterol after
gastrostomy. We suggest that a restoration of normal lipid metabolism should be
planned in patients with ALS.
PMID- 28422122
TI - Infant milk fat droplet size and coating affect postprandial responses in healthy
adult men: a proof-of-concept study.
AB - BACKGROUND/OBJECTIVES: Fat droplets in human milk (HM) are larger and surrounded
by a phospholipid membrane compared with infant milk formulas (IMF). Since the
physical structure of fat droplets might affect digestion and postprandial
metabolism, an IMF was developed more mimicking HM lipid structure than current
IMF. SUBJECTS/METHODS: A randomised, double-blind, crossover study was performed
in 29 fasted healthy men (aged 18-25 years, BMI: 18-25 kg/m2) to compare 5-hour
postprandial responses after consumption of an experimental IMF (Concept,
Nuturis) with a current IMF (Control). RESULTS: Postprandial triacylglycerol
(TAG) concentrations tended to increase faster after intake of Concept IMF
(P=0.054), but peaked 3 h after intakes at similar concentrations. ApoB48
increased steadily and peaked 3 h after consumption. Increases in plasma glucose
concentrations were comparable, but peak concentrations were reached faster after
consumption of Concept IMF (P<0.05). Peak insulin concentrations were higher and
reached earlier after intake of Concept IMF, causing a sharper decremental
glucose rebound (P<0.05) and an earlier time to nadir in non-esterified fatty
acid (NEFA) concentrations (P<0.01). Changes in plasma amino acids (AA), apoB100
and apoA1 were comparable. The incremental or decremental areas under-the-curve
did not differ between Concept and Control IMF. Satiety scores and changes in the
satiety hormones ghrelin and peptide YY were comparable, while cholecystokinin
responses were earlier and higher after consumption of Control IMF (P<0.05).
CONCLUSIONS: This proof-of-concept study suggests that fats and carbohydrates
from the Concept IMF with larger and phospholipid-coated fat droplets are more
rapidly absorbed than those from the current IMF.
PMID- 28422123
TI - Role of lifestyle factors in the epidemic of diabetes: lessons learnt from India.
AB - The prevalence of type 2 diabetes (T2D) is increasing steadily globally with the
largest increases occurring in developing countries like India. This is
attributed to the changes in the lifestyle factors, including physical inactivity
and unhealthy diet, both of which are modifiable. Existing evidence suggests that
increasing physical activity reduces the risk of T2D. Improving the built
environment can make it more conducive to people to increase physical activity.
There is also a rapid nutrition transition with consumption of diets with higher
intake of refined grains, higher fat, increased consumption of sugar and
sweetened beverages, and lower intake of fruits and vegetables. A multisectoral
approach promoting healthier diets and increasing physical activity can help in
slowing down the diabetic epidemic. However, this requires political will to make
necessary policy changes, as well as empowerment of the community, if the
preventive measures are to be sustainable and scalable.
PMID- 28422124
TI - Prevalence of type 2 diabetes and its complications in India and economic costs
to the nation.
AB - Diabetes, a major lifestyle disorder, has become a global burden, and the
prevalence rates are rising steeply in developing economies. Rapid socioeconomic
transition with urbanization and industrialization are the main causes for the
global diabetes epidemic. Among developing economies, the highest increase in
number of people with diabetes is in China followed by India. In India, the
epidemic of diabetes continue to increase and is experiencing a shift in diabetes
prevalence from urban to rural areas, the affluent to the less privileged and
from older to younger people. Diabetes is a progressive disorder leading to
complications, which are broadly divided into small vessel or microvascular
disease and large vessel or macrovascular disease. Microvascular complications
affect the inner part of the eye-the retina known as diabetic retinopathy, the
kidney termed as diabetic nephropathy and the peripheral nerves termed as
diabetic neuropathy. The macrovascular complications affect the heart, the brain
and the peripheral arteries termed as cardiovascular disease, cerebrovascular
disease and peripheral vascular disease, respectively. Given the lifelong
expenditure associated with diabetes and its complications, individuals, families
and the society are unable to cope with the economic, emotional and social
disease burden due to diabetes. The economic burden of diabetes can be reduced by
providing universal healthcare coverage, access to affordable medicines and early
detection and treatment of the disorder. This emphasizes the need for a multi
prolonged strategy to minimize the burden of diabetes and its complications.
PMID- 28422125
TI - Running exercise strengthens the intervertebral disc.
AB - There is currently no evidence that the intervertebral discs (IVDs) can respond
positively to exercise in humans. Some authors have argued that IVD metabolism in
humans is too slow to respond anabolically to exercise within the human lifespan.
Here we show that chronic running exercise in men and women is associated with
better IVD composition (hydration and proteoglycan content) and with IVD
hypertrophy. Via quantitative assessment of physical activity we further find
that accelerations at fast walking and slow running (2 m/s), but not high-impact
tasks, lower intensity walking or static positions, correlated to positive IVD
characteristics. These findings represent the first evidence in humans that
exercise can be beneficial for the IVD and provide support for the notion that
specific exercise protocols may improve IVD material properties in the spine. We
anticipate that our findings will be a starting point to better define exercise
protocols and physical activity profiles for IVD anabolism in humans.
PMID- 28422126
TI - Adrenergic-mediated loss of splenic marginal zone B cells contributes to
infection susceptibility after stroke.
AB - Infection is a major complication of acute stroke and causes increased mortality
and morbidity; however, current interventions do not prevent infection and
improve clinical outcome in stroke patients. The mechanisms that underlie
susceptibility to infection in these patients are unclear. Splenic marginal zone
(MZ) B cells are innate-like lymphocytes that provide early defence against
bacterial infection. Here we show experimental stroke in mice induces a marked
loss of MZ B cells, deficiencies in capturing blood-borne antigen and suppression
of circulating IgM. These deficits are accompanied by spontaneous bacterial lung
infection. IgM levels are similarly suppressed in stroke patients. beta
adrenergic receptor antagonism after experimental stroke prevents loss of splenic
MZ B cells, preserves IgM levels, and reduces bacterial burden. These findings
suggest that adrenergic-mediated loss of MZ B cells contributes to the infection
prone state after stroke and identify systemic B-cell disruption as a target for
therapeutic manipulation.
PMID- 28422127
TI - Differential Control of Asexual Development and Sterigmatocystin Biosynthesis by
a Novel Regulator in Aspergillus nidulans.
AB - The filamentous fungus Aspergillus nidulans primarily reproduces by forming
asexual spores called conidia and produces the mycotoxin sterigmatocystin (ST),
the penultimate precursor of aflatoxins. It has been known that asexual
development and ST production are tightly co-regulated by various regulatory
inputs. Here, we report that the novel regulator AslA with a C2H2 domain
oppositely regulates development and ST biosynthesis. Nullifying aslA resulted in
defective conidiation and reduced expression of brlA encoding a key activator of
asexual development, which indicates that AslA functions as an upstream activator
of brlA expression. aslA deletion additionally caused enhanced ST production and
expression of aflR encoding a transcriptional activator for ST biosynthetic
genes, suggesting that AslA functions as an upstream negative regulator of aflR.
Cellular and molecular studies showed that AslA has a trans-activation domain and
is localized in the nuclei of vegetative and developing cells but not in spores,
indicating that AslA is likely a transcription factor. Introduction of the aslA
homologs from distantly-related aspergilli complemented the defects caused by
aslA null mutation in A. nidulans, implying a functional conservancy of AslA. We
propose that AslA is a novel regulator that may act at the split control point of
the developmental and metabolic pathways.
PMID- 28422129
TI - GaAs1-xBix/GaNyAs1-y type-II quantum wells: novel strain-balanced
heterostructures for GaAs-based near- and mid-infrared photonics.
AB - The potential to extend the emission wavelength of photonic devices further into
the near- and mid-infrared via pseudomorphic growth on conventional GaAs
substrates is appealing for a number of communications and sensing applications.
We present a new class of GaAs-based quantum well (QW) heterostructure that
exploits the unusual impact of Bi and N on the GaAs band structure to produce
type-II QWs having long emission wavelengths with little or no net strain
relative to GaAs, while also providing control over important laser loss
processes. We theoretically and experimentally demonstrate the potential of GaAs1
xBix/GaNyAs1-y type-II QWs on GaAs and show that this approach offers optical
emission and absorption at wavelengths up to ~3 um utilising strain-balanced
structures, a first for GaAs-based QWs. Experimental measurements on a prototype
GaAs0.967Bi0.033/GaN0.062As0.938 structure, grown via metal-organic vapour phase
epitaxy, indicate good structural quality and exhibit both photoluminescence and
absorption at room temperature. The measured photoluminescence peak wavelength of
1.72 MUm is in good agreement with theoretical calculations and is one of the
longest emission wavelengths achieved on GaAs to date using a pseudomorphically
grown heterostructure. These results demonstrate the significant potential of
this new class of III-V heterostructure for long-wavelength applications.
PMID- 28422128
TI - Epidemiology of 45,616 suspect cases of Hand, Foot and Mouth Disease in
Chongqing, China, 2011-2015.
AB - Epidemiology and etiology of hand, foot, and mouth disease (HFMD) based on large
sample size or evaluation of detection for more enterovirus serotypes are not
well investigated in Chongqing of China. 45,616 suspect HFMD patients were
prospectively enrolled among whom 21,615 were laboratory confirmed HFMD cases
over a 5-year period (January 2011 to December 2015). Their epidemiological,
clinical, and laboratory data were extracted and stratified by month, age, sex,
disease severity, and enterovirus serotype. Subsequently 292 non-EV-A71/CV-A16
HFMD confirmed cases were randomly selected in three consecutive outbreaks to
detect CV-A6 and CV-A10, using RT-PCR. Results showed that the HFMD epidemic
peaked in early summer and autumn. The median age of onset was 2.45 years with a
male-to-female ratio of 1.54:1, and with children under 5 years of age accounting
for 92.54% of all confirmed cases. EV-A71 and CV-A16 infection accounted for only
36.05% (7793/21615) of total confirmed cases while EV-A71 accounted for 59.64%
(232/389) of severe cases. Importantly, the proportion of EV-A71 infection
generally increased with age which showed rapid growth in severe cases. CV-A6 and
CV-A10 were tested positive in Chongqing, but CV-A6 had greater positive rates of
62.33% while CV-A10 had 4.79% in non-EV-A71/CV-A16 HFMD confirmed cases.
PMID- 28422130
TI - Assessment of metabolic phenotypic variability in children's urine using 1H NMR
spectroscopy.
AB - The application of metabolic phenotyping in clinical and epidemiological studies
is limited by a poor understanding of inter-individual, intra-individual and
temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we
characterised short-term variability in urinary metabolites measured from 20
children aged 8-9 years old. Daily spot morning, night-time and pooled (50:50
morning and night-time) urine samples across six days (18 samples per child) were
analysed, and 44 metabolites quantified. Intraclass correlation coefficients
(ICC) and mixed effect models were applied to assess the reproducibility and
biological variance of metabolic phenotypes. Excellent analytical reproducibility
and precision was demonstrated for the 1H NMR spectroscopic platform (median CV
7.2%). Pooled samples captured the best inter-individual variability with an ICC
of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate,
3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate
exhibited the highest stability with over 50% of variance specific to the child.
The pooled sample was shown to capture the most inter-individual variance in the
metabolic phenotype, which is of importance for molecular epidemiology study
design. A substantial proportion of the variation in the urinary metabolome of
children is specific to the individual, underlining the potential of such data to
inform clinical and exposome studies conducted early in life.
PMID- 28422131
TI - Variants in CPLX1 in two families with autosomal-recessive severe infantile
myoclonic epilepsy and ID.
AB - For a large number of individuals with intellectual disability (ID), the
molecular basis of the disorder is still unknown. However, whole-exome sequencing
(WES) is providing more and more insights into the genetic landscape of ID. In
the present study, we performed trio-based WES in 311 patients with unsolved ID
and additional clinical features, and identified homozygous CPLX1 variants in
three patients with ID from two unrelated families. All displayed marked
developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar
cleft in addition. The encoded protein, complexin 1, is crucially involved in
neuronal synaptic regulation, and homozygous Cplx1 knockout mice have the
earliest known onset of ataxia seen in a mouse model. Recently, a homozygous
truncating variant in CPLX1 was suggested to be causative for migrating epilepsy
and structural brain abnormalities. ID was not reported although it cannot be
completely ruled out. However, the currently limited knowledge on CPLX1 suggests
that loss of complexin 1 function may lead to a complex but variable clinical
phenotype, and our findings encourage further investigations of CPLX1 in patients
with ID, developmental delay and myoclonic epilepsy to unravel the phenotypic
spectrum of carriers of CPLX1 variants.
PMID- 28422132
TI - Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG
and 16q24.3 microdeletion syndromes: 12 new cases.
AB - 16q24 deletion involving the ANKRD11 gene, ranging from 137 kb to 2 Mb, have been
associated with a microdeletion syndrome characterized by variable cognitive
impairment, autism spectrum disorder, facial dysmorphisms with dental anomalies,
brain abnormalities essentially affecting the corpus callosum and short stature.
On the other hand, patients carrying either deletions encompassing solely ANKRD11
or its loss-of-function variants were reported in association with the KBG
syndrome, characterized by a very similar phenotype, including mild-to-moderate
intellectual disability, short stature and macrodontia of upper incisors, with
inter and intrafamilial variability. To assess whether the haploinsufficiency of
ANKRD11-flanking genes, such as ZFPM1, CDH15 and ZNF778, contributed to either
the severity of the neurological impairment or was associated with other clinical
features, we collected 12 new cases with a 16q24.2q24.3 deletion (de novo in 11
cases), ranging from 343 kb to 2.3 Mb. In 11 of them, the deletion involved the
ANKRD11 gene, whereas in 1 case only flanking genes upstream to it were deleted.
By comparing the clinical and genetic features of our patients with those
previously reported, we show that the severity of the neurological phenotype and
the frequency of congenital heart defects characterize the deletions that,
besides ANKRD11, contain ZFPM1, CDH15 and ZNF778 as well. Moreover, the presence
of thrombocytopenia and astigmatism should be taken into account to distinguish
between 16q24 microdeletion syndrome and KBG syndrome. The single patient not
deleted for ANKRD11, whose phenotype is characterized by milder psychomotor
delay, cardiac congenital malformation, thrombocytopenia and astigmatism,
confirms all this data.
PMID- 28422133
TI - Gene-set analysis shows association between FMRP targets and autism spectrum
disorder.
AB - Autism spectrum disorder (ASD) is a heterogeneous group of disorders
characterized by problems with social interaction, communication, and repetitive
and restricted behavior. Despite its high heritability and the substantial
progress made in elucidating genetic associations, the corresponding biological
mechanisms are largely unknown. Our objective is to investigate the contribution
of common genetic variation to biological pathways functionally involved in ASD.
We conducted gene-set analyses to identify ASD-associated functional biological
pathways using the statistical tools MAGMA and INRICH. Gene-set selection was
based on previously reported associations with psychiatric disorders and resulted
in testing of specific synaptic and glial sets, a glutamate pathway gene-set,
mitochondrial gene-sets and gene-sets consisting of fragile X mental retardation
protein (FMRP) targets. In total 32 gene-sets were tested. We used Psychiatric
Genomics Consortium genome-wide association studies summary statistics of ASD.
The study is based on the largest ASD sample to date (N=5305). We found one
significantly associated gene-set consisting of FMRP-targeting transcripts
(MAGMA: p corr.=0.014, INRICH: p corr.=0.031; all competitive P-values). The
results indicate the involvement of FMRP-targeted transcripts in ASD in common
genetic variation. This novel finding is in line with the literature as FMRP has
been linked to fragile X syndrome, ASD and cognitive development in whole-exome
sequencing and copy number variant studies. This gene-set has also been linked to
Schizophrenia suggesting that FMRP-targeted transcripts might be involved in a
general mechanism with shared genetic etiology between psychiatric disorders.
PMID- 28422134
TI - Genetic structure and signatures of selection in grey reef sharks (Carcharhinus
amblyrhynchos).
AB - With overfishing reducing the abundance of marine predators in multiple marine
ecosystems, knowledge of genetic structure and local adaptation may provide
valuable information to assist sustainable management. Despite recent
technological advances, most studies on sharks have used small sets of neutral
markers to describe their genetic structure. We used 5517 nuclear single
nucleotide polymorphisms (SNPs) and a mitochondrial DNA (mtDNA) gene to
characterize patterns of genetic structure and detect signatures of selection in
grey reef sharks (Carcharhinus amblyrhynchos). Using samples from Australia,
Indonesia and oceanic reefs in the Indian Ocean, we established that large
oceanic distances represent barriers to gene flow, whereas genetic
differentiation on continental shelves follows an isolation by distance model. In
Australia and Indonesia differentiation at nuclear SNPs was weak, with coral
reefs acting as stepping stones maintaining connectivity across large distances.
Differentiation of mtDNA was stronger, and more pronounced in females, suggesting
sex-biased dispersal. Four independent tests identified a set of loci putatively
under selection, indicating that grey reef sharks in eastern Australia are likely
under different selective pressures to those in western Australia and Indonesia.
Genetic distances averaged across all loci were uncorrelated with genetic
distances calculated from outlier loci, supporting the conclusion that different
processes underpin genetic divergence in these two data sets. This pattern of
heterogeneous genomic differentiation, suggestive of local adaptation, has
implications for the conservation of grey reef sharks; furthermore, it highlights
that marine species showing little genetic differentiation at neutral loci may
exhibit patterns of cryptic genetic structure driven by local selection.
PMID- 28422136
TI - The relationship between climate change and the endangered rainforest shrub
Triunia robusta (Proteaceae) endemic to southeast Queensland, Australia.
AB - Threatened species in rainforests may be vulnerable to climate change, because of
their potentially narrow thermal tolerances, small population sizes and
restricted distributions. This study modelled climate induced changes on the
habitat distribution of the endangered rainforest plant Triunia robusta, endemic
to southeast Queensland, Australia. Species distribution models were developed
for eastern Australia at 250 m grids and southeast Queensland at 25 m grids using
ground-truthed presence records and environmental predictor data. The species'
habitat distribution under the current climate was modelled, and the future
potential habitat distributions were projected for the epochs 2030, 2050 and
2070. The eastern Australia model identified several spatially disjunct, broad
habitat areas of coastal eastern Australia consistent with the current
distribution of rainforests, and projected a southward and upslope contraction
driven mainly by average temperatures exceeding current range limits. The
southeast Queensland models suggest a dramatic upslope contraction toward
locations where the majority of known populations are found. Populations located
in the Sunshine Coast hinterland, consistent with past rainforest refugia, are
likely to persist long-term. Upgrading the level of protection for less formal
nature reserves containing viable populations is a high priority to better
protect refugial T. robusta populations with respect to climate change.
PMID- 28422135
TI - Genomic evidence of hybridization between two independent invasions of European
green crab (Carcinus maenas) in the Northwest Atlantic.
AB - Invasive species have been associated with significant negative impacts in their
introduced range often outcompeting native species, yet the long-term
evolutionary dynamics of biological invasions are not well understood.
Hybridization, either among waves of invasion or between native and introduced
populations, could alter the ecological and evolutionary impacts of invasions yet
has rarely been studied in marine invasive species. The European green crab
(Carcinus maenas) invaded eastern North America twice from northern and southern
locations in its native range. Here we examine the frequency of hybridization
among these two distinct invasions at locations from New Jersey, USA to
Newfoundland, Canada using restriction-site-associated DNA sequencing (RAD-seq),
microsatellite loci and cytochrome c oxidase subunit I mitochondrial DNA (mtDNA)
sequences. We used Bayesian clustering and hybrid assignment analyses to
investigate hybridization between the northern and southern populations. Of the
samples analyzed, six locations contained at least one hybrid individual, while
two locations were characterized by extensive hybridization, with 95% of
individuals collected from Placentia Bay, Newfoundland being hybrids (mostly F2)
and 90% of individuals from Kejimkujik, Nova Scotia being classified as hybrids,
mostly backcrosses to the northern ecotype. The presence of both F2 hybrids and
backcrossed individuals suggests that these hybrids are viable and introgression
is occurring between invasions. Our results provide insight into the demographic
and evolutionary consequences of hybridization between independent invasions, and
will inform the management of green crabs in eastern North America.
PMID- 28422137
TI - Effective in vivo therapeutic IgG antibody against VP3 of enterovirus 71 with
receptor-competing activity.
AB - Passive immunization is an effective option for treatment against hand, foot and
mouth disease caused by EV71, especially with cross-neutralizing IgG monoclonal
antibodies. In this study, an EV71-specific IgG2a antibody designated 5H7 was
identified and characterized. 5H7 efficiently neutralizes the major EV71
genogroups (A, B4, C2, C4). The conformational epitope of 5H7 was mapped to the
highly conserved amino acid position 74 on VP3 capsid protein using escape
mutants. Neutralization with 5H7 is mediated by the inhibition of viral
attachment, as revealed by virus-binding and post-attachment assays. In a
competitive pull-down assay with SCARB2, 5H7 blocks the receptor-binding site on
EV71 for virus neutralization. Passive immunization of chimeric 5H7 protected
100% of two-week-old AG129 mice from lethal challenge with an EV71 B4 strain for
both prophylactic and therapeutic treatments. In contrast, 10D3, a previously
reported neutralizing antibody that takes effect after virus attachment, could
only confer prophylactic protection. These results indicate that efficient
interruption of viral attachment is critical for effective therapeutic activity
with 5H7. This report documents a novel universal neutralizing IgG antibody for
EV71 therapeutics and reveals the underlying mechanism.
PMID- 28422139
TI - High pesticide risk to honey bees despite low focal crop pollen collection during
pollination of a mass blooming crop.
AB - Honey bees provide critical pollination services for many agricultural crops.
While the contribution of pesticides to current hive loss rates is debated,
remarkably little is known regarding the magnitude of risk to bees and mechanisms
of exposure during pollination. Here, we show that pesticide risk in recently
accumulated beebread was above regulatory agency levels of concern for acute or
chronic exposure at 5 and 22 of the 30 apple orchards, respectively, where we
placed 120 experimental hives. Landscape context strongly predicted focal crop
pollen foraging and total pesticide residues, which were dominated by fungicides.
Yet focal crop pollen foraging was a poor predictor of pesticide risk, which was
driven primarily by insecticides. Instead, risk was positively related to
diversity of non-focal crop pollen sources. Furthermore, over 60% of pesticide
risk was attributed to pesticides that were not sprayed during the apple bloom
period. These results suggest the majority of pesticide risk to honey bees
providing pollination services came from residues in non-focal crop pollen,
likely contaminated wildflowers or other sources. We suggest a greater
understanding of the specific mechanisms of non-focal crop pesticide exposure is
essential for minimizing risk to bees and improving the sustainability of grower
pest management programs.
PMID- 28422138
TI - Abnormal resting-state functional connectivity in the orbitofrontal cortex of
heroin users and its relationship with anxiety: a pilot fNIRS study.
AB - Drug addiction is widely linked to the orbitofrontal cortex (OFC), which is
essential for regulating reward-related behaviors, emotional responses, and
anxiety. Over the past two decades, neuroimaging has provided significant
contributions revealing functional and structural alternations in the brains of
drug addicts. However, the underlying neural mechanism in the OFC and its
correlates with drug addiction and anxiety still require further elucidation. We
first presented a pilot investigation to examine local networks in OFC regions
through resting-state functional connectivity (rsFC) using functional near
infrared spectroscopy (fNIRS) from eight abstinent addicts in a heroin-dependent
group (HD) and seven subjects in a control group (CG). We discovered that the HDs
manifested enhanced interhemispheric correlation and rsFC. Moreover, small
worldness was explored in the brain networks. In addition to the altered rsFC in
the OFC networks, our examinations demonstrated associations in the functional
connectivity between the left inferior frontal gyrus and other OFC regions
related to anxiety in the HDs. The study provides important preliminary evidence
of the complex OFC networks in heroin addiction and suggests neural correlates of
anxiety. It opens a window in application of fNIRS to predict psychiatric
trajectories and may create new insights into neural adaptations resulting from
chronic opiate intake.
PMID- 28422140
TI - The evolutionary history of bears is characterized by gene flow across species.
AB - Bears are iconic mammals with a complex evolutionary history. Natural bear
hybrids and studies of few nuclear genes indicate that gene flow among bears may
be more common than expected and not limited to polar and brown bears. Here we
present a genome analysis of the bear family with representatives of all living
species. Phylogenomic analyses of 869 mega base pairs divided into 18,621 genome
fragments yielded a well-resolved coalescent species tree despite signals for
extensive gene flow across species. However, genome analyses using different
statistical methods show that gene flow is not limited to closely related species
pairs. Strong ancestral gene flow between the Asiatic black bear and the ancestor
to polar, brown and American black bear explains uncertainties in reconstructing
the bear phylogeny. Gene flow across the bear clade may be mediated by
intermediate species such as the geographically wide-spread brown bears leading
to large amounts of phylogenetic conflict. Genome-scale analyses lead to a more
complete understanding of complex evolutionary processes. Evidence for extensive
inter-specific gene flow, found also in other animal species, necessitates
shifting the attention from speciation processes achieving genome-wide
reproductive isolation to the selective processes that maintain species
divergence in the face of gene flow.
PMID- 28422141
TI - Erratum: Maternally expressed NLRP2 links the subcortical maternal complex (SCMC)
to fertility, embryogenesis and epigenetic reprogramming.
PMID- 28422143
TI - Dissecting the genetic architecture of Fusarium verticillioides seed rot
resistance in maize by combining QTL mapping and genome-wide association
analysis.
AB - Fusarium verticillioides can be transmitted via seeds and cause systemic
infection in maize (Zea mays L.); its mycotoxin has harmful effects on animal and
human health. We combined QTL mapping in recombinant inbred line (RIL)
populations with a genome-wide association study (GWAS) of 217 diverse maize
lines using 224,152 single nucleotide polymorphisms (SNPs) under controlled
conditions to determine the genetic architecture of F. verticillioides seed rot
(FSR) resistance. Our study identified 8 quantitative trait loci (QTLs) and 43
genes associated with 57 SNPs that were correlated with FSR resistance through
linkage mapping and GWAS, respectively. Among these, there were three candidate
genes, namely GRMZM2G0081223, AC213654.3_FG004, and GRMZM2G099255, which were
detected in both linkage mapping and GWAS. Furthermore, the near-isogenic lines
(NILs) containing GRMZM2G0081223, which also had a susceptible parent background,
were found to have a significantly improved level of resistance. In addition, the
expression profile of the three candidate genes revealed that they all respond to
the infection following inoculation with F. verticillioides. These genetic
analyses indicate that FSR resistance is controlled by loci with minor effect,
and the polymerization breeding of lines with beneficial alleles and candidate
genes could improve FSR resistance in maize.
PMID- 28422142
TI - G protein-coupled KISS1 receptor is overexpressed in triple negative breast
cancer and promotes drug resistance.
AB - Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor
alpha, progesterone receptor and human epidermal growth factor receptor 2 (HER2).
TNBC patients lack targeted therapies, as they fail to respond to endocrine and
anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and
survival is limited due to the development of resistance to available
chemotherapies and resultant metastases. The mechanisms regulating tumor
resistance are poorly understood. Here we demonstrate that the G protein-coupled
kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells. KISS1R binds
kisspeptins, peptide products of the KISS1 gene and in numerous cancers, this
signaling pathway plays anti-metastatic roles. However, in TNBC, KISS1R promotes
tumor invasion. We show that KISS1 and KISS1R mRNA and KISS1R protein are
upregulated in TNBC tumors, compared to normal breast tissue. KISS1R signaling
promotes drug resistance by increasing the expression of efflux drug transporter,
breast cancer resistance protein (BCRP) and by inducing the activity and
transcription of the receptor tyrosine kinase, AXL. BCRP and AXL transcripts are
elevated in TNBC tumors, compared to normal breast, and TNBC tumors expressing
KISS1R also express AXL and BCRP. Thus, KISS1R represents a potentially novel
therapeutic target to restore drug sensitivity in TNBC patients.
PMID- 28422144
TI - Risk and Prediction of Sudden Cardiac Death and Ventricular Arrhythmias for
Patients with Atrial Fibrillation - A Nationwide Cohort Study.
AB - Sudden cardiac death (SCD) is the most devastating manifestation of ventricular
arrhythmias (VAs), and is the leading cause of mortality among atrial
fibrillation (AF) patients. The goal of the present study was to investigate the
incidence of SCD/VAs amongst patients with and without AF. We also aimed to
identify important risk factors of SCD/VAs among AF patients. Using the "National
Health Insurance Research Database" in Taiwan, a total of 352,656 AF and 352,656
non-AF patients without antecedent SCD/VAs were identified. The annual risk of
SCD/VAs was higher in AF than non-AF groups (0.97% versus 0.47%) with an adjusted
hazard ratio (HR) of 1.64. The increased risk of SCD/VAs in AF patients was
consistently observed in different age strata, various comorbidities and patients
without use of class I/III anti-arrhythmic drugs or digoxin. Among AF patients,
age >=75 years, congestive heart failure, hypertension, diabetes mellitus,
previous stroke/transient ischemic attack, vascular diseases, chronic kidney
disease and chronic obstructive pulmonary disease were important risk factors for
SCD/VAs. In conclusion, the risk of SCD/VAs amongst AF patients was 1.64-fold
higher compared to non-AF patients, which was associated with the number of
clinical risk factors associated with the particular AF patient.
PMID- 28422145
TI - Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal
Markets.
AB - As the most widely used illicit drug worldwide, and as a source of numerous under
studied pharmacologically-active compounds, a precise understanding of
variability in psychological and physiological effects of Cannabis varieties is
essential. The National Institute on Drug Abuse (NIDA) is designated as the sole
legal producer of Cannabis for use in US research studies. We sought to compare
the chemical profiles of Cannabis varieties that are available to consumers in
states that have state-legalized use versus what is available to researchers
interested in studying the plant and its effects. Our results demonstrate that
the federally-produced Cannabis has significantly less variety and lower
concentrations of cannabinoids than are observed in state-legal U.S.
dispensaries. Most dramatically, NIDA's varieties contain only 27% of the THC
levels and as much as 11-23 times the Cannabinol (CBN) content compared to what
is available in the state-legal markets. Research restricted to using the current
range of federally-produced Cannabis thus may yield limited insights into the
chemical, biological and pharmacological properties, and medical potential of
material that is available in the state markets. Investigation is urgently needed
on the full diversity of Cannabis chemotypes known to be available to the public.
PMID- 28422146
TI - A study of the effects of synthesis conditions on Li5FeO4/carbon nanotube
composites.
AB - Li5FeO4/carbon nanotube (LFO/CNT) composites composed of sub-micron sized LFO and
a nanocarbon with high electrical conductivity were successfully synthesized for
the use as lithium ion predoping source in lithium ion cells. The phase of LFO in
the composite was found to be very sensitive to the synthesis conditions, such as
the heat treatment temperature, type of lithium salt, and physical state of the
precursors (powder or pellet), due to the carbothermic reduction of Fe3O4 by CNTs
during high temperature solid state reaction. Under optimized synthesis
conditions, LFO/CNT composites could be synthesized without the formation of
impurities. To the best of our knowledge, this is the first report on the
synthesis and characterization of a sub-micron sized LFO/CNT composites.
PMID- 28422147
TI - Construction of a high-density linkage map and fine mapping of QTLs for growth
and gonad related traits in blunt snout bream.
AB - High-density genetic maps based on SNPs are essential for fine mapping loci
controlling specific traits for fish species. Using restriction-site associated
DNA tag sequencing (RAD-Seq) technology, we identified 42,784 SNPs evenly
distributed across the Megalobrama amblycephala genome. Based on 2 parents and
187 intra-specific hybridization progenies, a total of 14,648 high-confidence
SNPs were assigned to 24 consensus linkage groups (LGs) of maternal and paternal
map. The total length of the integrated map was 3,258.38 cM with an average
distance of 0.57 cM among 5676 effective loci, thereby representing the first
high-density genetic map reported for M. amblycephala. A total of eight positive
quantitative trait loci (QTLs) were detected in QTL analysis. Of that, five QTL
explained >=35% of phenotypic variation for growth traits and three QTL explained
>=16% phenotypic variation for gonad related traits. A total of 176 mapped
markers had significant hits in the zebrafish genome and almost all of the 24
putative-chromosomes of M. amblycephala were in relatively conserved synteny with
chromosomes of zebrafish. Almost all M. amblycephala and zebrafish chromosomes
had a 1:1 correspondence except for putative-chromosome 4, which mapped to two
chromosomes of zebrafish caused by the difference in chromosome numbers between
two species.
PMID- 28422148
TI - Chemical and Bioactive Profiling, and Biological Activities of Coral Fungi from
Northwestern Himalayas.
AB - Ramaria Fr. and Clavaria L. are the two major genera of coral mushrooms within
families Gomphaceae and Clavariaceae, respectively. Besides having important role
in forest ecology, some species of these are reported to possess high
nutraceutical and bioactive potential. There is a hidden diversity of coral
mushrooms in Northwestern Himalayas. Present studies describe the detailed
biochemical profiling and antioxidant, and antibacterial activities of twelve
coral mushroom species. Biochemical profiling of nutrients and nutraceuticals was
done with standard techniques and by using HPLC, UPLC and GC. Experiments were
also conducted to check the toxic metals detection. Antioxidant activities were
calculated using EC50 values from mushroom extracts. Antibacterial activities
were checked on six pathogenic bacterial strains through minimum inhibition
concenterations. Although, differences were observed in the net values of
individual species but all the species were found to be rich in protein, macro
and micro minerals, carbohydrates, unsaturated fatty acids, essential amino
acids, phenolics, tocopherols, anthocynadins and carotenoids. All the species
showed significant antioxidant and antibacterial activities. These species are
reported to free from heavy toxic metals. Present studies will open the way for
their large scale commercial exploitations and use in pharmaceutical industries
as antioxidant, antibacterial and nutraceutical constituents.
PMID- 28422149
TI - Monitoring seasonal influenza epidemics by using internet search data with an
ensemble penalized regression model.
AB - Seasonal influenza epidemics cause serious public health problems in China.
Search queries-based surveillance was recently proposed to complement traditional
monitoring approaches of influenza epidemics. However, developing robust
techniques of search query selection and enhancing predictability for influenza
epidemics remains a challenge. This study aimed to develop a novel ensemble
framework to improve penalized regression models for detecting influenza
epidemics by using Baidu search engine query data from China. The ensemble
framework applied a combination of bootstrap aggregating (bagging) and rank
aggregation method to optimize penalized regression models. Different algorithms
including lasso, ridge, elastic net and the algorithms in the proposed ensemble
framework were compared by using Baidu search engine queries. Most of the
selected search terms captured the peaks and troughs of the time series curves of
influenza cases. The predictability of the conventional penalized regression
models were improved by the proposed ensemble framework. The elastic net
regression model outperformed the compared models, with the minimum prediction
errors. We established a Baidu search engine queries-based surveillance model for
monitoring influenza epidemics, and the proposed model provides a useful tool to
support the public health response to influenza and other infectious diseases.
PMID- 28422150
TI - Elucidation of crystal and electronic structures within highly strained BiFeO3 by
transmission electron microscopy and first-principles simulation.
AB - Crystal and electronic structures of ~380 nm BiFeO3 film grown on LaAlO3
substrate are comprehensively studied using advanced transmission electron
microscopy (TEM) technique combined with first-principles theory. Cross-sectional
TEM images reveal the BiFeO3 film consists of two zones with different crystal
structures. While zone II turns out to have rhombohedral BiFeO3, the crystal
structure of zone I matches none of BiFeO3 phases reported experimentally or
predicted theoretically. Detailed electron diffraction analysis combined with
first-principles calculation allows us to determine that zone I displays an
orthorhombic-like monoclinic structure with space group of Cm (=8). The growth
mechanism and electronic structure in zone I are further discussed in comparison
with those of zone II. This study is the first to provide an experimentally
validated complete crystallographic detail of a highly strained BiFeO3 that
includes the lattice parameter as well as the basis atom locations in the unit
cell.
PMID- 28422151
TI - Determinants of Thermostability in Serine Hydroxymethyltransferase Identified by
Principal Component Analysis.
AB - Protein thermostability has received growing attention in recent years. Little is
known about the determinants of thermal resistance in individual protein
families. However, it is known that the mechanism is family-dependent and not
identical for all proteins. We present a multivariate statistical analysis to
find the determinants of thermostability in one protein family, the serine
hydroxymethyltransferase family. Based on principal component analysis, we
identified three amino acid fragments as the potential determinants of
thermostability. The correlation coefficients between all the putative fragments
and the protein thermostability were significant according to multivariable
linear regression. Within the fragments, four critical amino acid positions were
identified, and they indicated the contributions of Leu, Val, Lys, Asp, Glu, and
Phe to thermostability. Moreover, we analyzed the insertions/deletions of amino
acids in the sequence, which showed that thermophilic SHMTs tend to insert or
delete residues in the C-terminal domain rather than the N-terminal domain. Our
study provided a promising approach to perform a preliminary search for the
determinants of thermophilic proteins. It could be extended to other protein
families to explore their own strategies for adapting to high temperature.
PMID- 28422152
TI - Towards automatic pulmonary nodule management in lung cancer screening with deep
learning.
AB - The introduction of lung cancer screening programs will produce an unprecedented
amount of chest CT scans in the near future, which radiologists will have to read
in order to decide on a patient follow-up strategy. According to the current
guidelines, the workup of screen-detected nodules strongly relies on nodule size
and nodule type. In this paper, we present a deep learning system based on multi
stream multi-scale convolutional networks, which automatically classifies all
nodule types relevant for nodule workup. The system processes raw CT data
containing a nodule without the need for any additional information such as
nodule segmentation or nodule size and learns a representation of 3D data by
analyzing an arbitrary number of 2D views of a given nodule. The deep learning
system was trained with data from the Italian MILD screening trial and validated
on an independent set of data from the Danish DLCST screening trial. We analyze
the advantage of processing nodules at multiple scales with a multi-stream
convolutional network architecture, and we show that the proposed deep learning
system achieves performance at classifying nodule type that surpasses the one of
classical machine learning approaches and is within the inter-observer
variability among four experienced human observers.
PMID- 28422153
TI - Clinical-pharmacogenetic models for personalized cancer treatment: application to
malignant mesothelioma.
AB - Large interindividual differences in treatment outcome are observed in cancer
patients undergoing chemotherapy. Our aim was to develop and validate clinical
pharmacogenetic prediction models of gemcitabine/cisplatin or
pemetrexed/cisplatin treatment outcome and develop an algorithm for genotype
based treatment recommendations in malignant mesothelioma (MM). We genotyped 189
MM patients for polymorphisms in gemcitabine, pemetrexed and cisplatin
metabolism, transport and drug target genes and DNA repair pathways. To build
respective clinical-pharmacogenetic models, pharmacogenetic scores were assigned
by rounding regression coefficients. Gemcitabine/cisplatin model was based on
training group of 71 patients and included CRP, histological type, performance
status, RRM1 rs1042927, ERCC2 rs13181, ERCC1 rs3212986, and XRCC1 rs25487.
Patients with higher score had shorter progression-free (PFS) and overall
survival (P < 0.001). This model's sensitivity was 0.615 and specificity 0.812.
In independent validation group of 66 patients the sensitivity and specificity
were 0.667 and 0.641, respectively. Pemetrexed/cisplatin model was based on 57
patients and included CRP, MTHFD1 rs2236225, and ABCC2 rs2273697. Patients with
higher score had worse response and shorter PFS (P < 0.001). This model's
sensitivity was 0.750 and specificity 0.607. In independent validation group of
20 patients the sensitivity and specificity were 0.889 and 0.500, respectively.
The proposed algorithm based on these models could enable the choice of the most
effective chemotherapy for 85.5% of patients and lead to improved treatment
outcome in MM.
PMID- 28422154
TI - Integration of liver gene co-expression networks and eGWAs analyses highlighted
candidate regulators implicated in lipid metabolism in pigs.
AB - In the present study, liver co-expression networks and expression Genome Wide
Association Study (eGWAS) were performed to identify DNA variants and molecular
pathways implicated in the functional regulatory mechanisms of meat quality
traits in pigs. With this purpose, the liver mRNA expression of 44 candidates
genes related with lipid metabolism was analysed in 111 Iberian x Landrace
backcross animals. The eGWAS identified 92 eSNPs located in seven chromosomal
regions and associated with eight genes: CROT, CYP2U1, DGAT1, EGF, FABP1, FABP5,
PLA2G12A, and PPARA. Remarkably, cis-eSNPs associated with FABP1 gene expression
which may be determining the C18:2(n-6)/C18:3(n-3) ratio in backfat through the
multiple interaction of DNA variants and genes were identified. Furthermore, a
hotspot on SSC8 associated with the gene expression of eight genes was identified
and the TBCK gene was pointed out as candidate gene regulating it. Our results
also suggested that the PI3K-Akt-mTOR pathway plays an important role in the
control of the analysed genes highlighting nuclear receptors as the NR3C1 or
PPARA. Finally, sex-dimorphism associated with hepatic lipid metabolism was
identified with over-representation of female-biased genes. These results
increase our knowledge of the genetic architecture underlying fat composition
traits.
PMID- 28422155
TI - In vitro biocompatibility study of sub-5 nm silica-coated magnetic iron oxide
fluorescent nanoparticles for potential biomedical application.
AB - Magnetic iron oxide nanoparticles (IONPs), for their intriguing properties, have
attracted a great interest as they can be employed in many different biomedical
applications. In this multidisciplinary study, we synthetized and characterized
ultrafine 3 nm superparamagnetic water-dispersible nanoparticles. By a facile and
inexpensive one-pot approach, nanoparticles were coated with a shell of silica
and contemporarily functionalized with fluorescein isothiocyanate (FITC) dye. The
obtained sub-5 nm silica-coated magnetic iron oxide fluorescent (sub-5 SIO-Fl)
nanoparticles were assayed for cellular uptake, biocompatibility and cytotoxicity
in a human colon cancer cellular model. By confocal microscopy analysis we
demonstrated that nanoparticles as-synthesized are internalized and do not
interfere with the CaCo-2 cell cytoskeletal organization nor with their cellular
adhesion. We assessed that they do not exhibit cytotoxicity, providing evidence
that they do not affect shape, proliferation, cellular viability, cell cycle
distribution and progression. We further demonstrated at molecular level that
these nanoparticles do not interfere with the expression of key differentiation
markers and do not affect pro-inflammatory cytokines response in Caco-2 cells.
Overall, these results showed the in vitro biocompatibility of the sub-5 SIO-Fl
nanoparticles promising their safe employ for diagnostic and therapeutic
biomedical applications.
PMID- 28422156
TI - Anticancer properties of a defensin like class IId bacteriocin Laterosporulin10.
AB - Laterosporulin10 (LS10) is a defensin like peptide from Brevibacillus sp. strain
SKDU10 that inhibited microbial pathogens. However, in this study, anticancer
activity of LS10 was examined against different cancer cell lines and compared
with normal cells. LS10 displayed cytotoxicity against cancer cells like MCF-7,
HEK293T, HT1080, HeLa and H1299 at below 10 MUM concentration, but not against
prostate epithelium cells RWPE-1. Additionally, no hemolysis was observed at
significantly higher concentration compared to IC50 values observed for different
cancer cell lines. Release of lactate dehydrogenase from cancer cell lines at 15
MUM concentration upon 120 min treatment indicated the lytic ability of LS10.
Accordingly, electron microscopy experiments also confirmed the necrotic effect
of LS10 at 15 MUM concentration against cancer cells. Furthermore, flow cytometry
analysis of treated cancer cell lines revealed that LS10 induce apoptosis even at
2.5 MUM concentration. Nevertheless, RWPE-1 cells remained viable even at 20 MUM
concentration. These results provide evidence that LS10 is an anticancer
bacteriocin, which causes apoptotic and necrotic death of cancer cells at lower
and higher concentrations, respectively. Taken all results together, the present
study signifies that LS10 is an anticancer peptide that could be further
developed for therapeutic applications.
PMID- 28422157
TI - Detection of a new pyrethroid resistance mutation (V410L) in the sodium channel
of Aedes aegypti: a potential challenge for mosquito control.
AB - The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is
the principal vector of dengue, yellow fever, Zika and Chikungunya viruses.
Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes,
despite the development of pyrethroid resistance in many mosquito populations
worldwide. Here, we report a Brazilian strain of A. aegypti with high levels
(approximately 100-60,000 fold) of resistance to both type I and type II
pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel
from this resistant strain. This study is the first report of the V410L mutation
in mosquitoes. Alone or in combination with the F1534C mutation, the V410L
mutation drastically reduced the sensitivity of mosquito sodium channels
expressed in Xenopus oocytes to both type I and type II pyrethroids. The V410L
mutation presents a serious challenge for the control of A. aegypti and will
compromise the use of pyrethroids for the control of A. aegypti in Brazil;
therefore, early monitoring of the frequency of the V410L mutation will be a key
resistance management strategy to preserve the effectiveness of pyrethroid
insecticides.
PMID- 28422158
TI - Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion
that is highly dependent upon oxidative stress.
AB - Isothiocyanates, such as phenethyl isothiocyanate (PEITC), are formed following
the consumption of cruciferous vegetables and generate reactive oxygen species
(ROS) that lead to the induction of cytoprotective genes such as the UDP
glucuronosyltransferases (UGTs). The induction of ROS activates the Nrf2-Keap 1
pathway leading to the induction of genes through antioxidant response elements
(AREs). UGT1A1, the sole enzyme responsible for the metabolism of bilirubin, can
be induced following activation of Nrf2. When neonatal humanized UGT1 (hUGT1)
mice, which exhibit severe levels of total serum bilirubin (TSB) because of a
developmental delay in expression of the UGT1A1 gene, were treated with PEITC,
TSB levels were reduced. Liver and intestinal UGT1A1 were induced, along with
murine CYP2B10, a consensus CAR target gene. In both neonatal and adult hUGT1/Car
/- mice, PEITC was unable to induce CYP2B10. A similar result was observed
following analysis of UGT1A1 expression in liver. However, TSB levels were still
reduced in hUGT1/Car-/- neonatal mice because of ROS induction of intestinal
UGT1A1. When oxidative stress was blocked by exposing mice to N-acetylcysteine,
induction of liver UGT1A1 and CYP2B10 by PEITC was prevented. Thus, new findings
in this report link an important role in CAR activation that is dependent upon
oxidative stress.
PMID- 28422159
TI - Spastic paraplegia-linked phospholipase PAPLA1 is necessary for development,
reproduction, and energy metabolism in Drosophila.
AB - The human PAPLA1 phospholipase family is associated with hereditary spastic
paraplegia (HSP), a neurodegenerative syndrome characterized by progressive
spasticity and weakness of the lower limbs. Taking advantage of a new Drosophila
PAPLA1 mutant, we describe here novel functions of this phospholipase family in
fly development, reproduction, and energy metabolism. Loss of Drosophila PAPLA1
reduces egg hatchability, pre-adult viability, developmental speed, and impairs
reproductive functions of both males and females. In addition, our work describes
novel metabolic roles of PAPLA1, manifested as decreased food intake, lower
energy expenditure, and reduced ATP levels of the mutants. Moreover, PAPLA1 has
an important role in the glycogen metabolism, being required for expression of
several regulators of carbohydrate metabolism and for glycogen storage. In
contrast, global loss of PAPLA1 does not affect fat reserves in adult flies.
Interestingly, several of the PAPLA1 phenotypes in fly are reminiscent of
symptoms described in some HSP patients, suggesting evolutionary conserved
functions of PAPLA1 family in the affected processes. Altogether, this work
reveals novel physiological functions of PAPLA1, which are likely evolutionary
conserved from flies to humans.
PMID- 28422160
TI - Efficient electrical control of thin-film black phosphorus bandgap.
AB - Recently rediscovered black phosphorus is a layered semiconductor with promising
electronic and photonic properties. Dynamic control of its bandgap can allow for
the exploration of new physical phenomena. However, theoretical investigations
and photoemission spectroscopy experiments indicate that in its few-layer form,
an exceedingly large electric field in the order of several volts per nanometre
is required to effectively tune its bandgap, making the direct electrical control
unfeasible. Here we reveal the unique thickness-dependent bandgap tuning
properties in intrinsic black phosphorus, arising from the strong interlayer
electronic-state coupling. Furthermore, leveraging a 10 nm-thick black
phosphorus, we continuously tune its bandgap from ~300 to below 50 meV, using a
moderate displacement field up to 1.1 V nm-1. Such dynamic tuning of bandgap may
not only extend the operational wavelength range of tunable black phosphorus
photonic devices, but also pave the way for the investigation of electrically
tunable topological insulators and semimetals.
PMID- 28422161
TI - Impact of low-temperature, overcast and rainy weather during the reproductive
growth stage on lodging resistance of rice.
AB - The objectives of this study were to explore the mechanism by which the lodging
resistance of the rice population during the late growth period responds to low
temperature, overcast and rainy weather during the reproductive growth stage.
Field experiments were conducted using indica rice Yliangyou2 (lodging-resistance
variety), IIyou084 (lodging-susceptible variety) and japonica rice Wuyunjing23
(lodging-resistance variety) and W3668 (lodging- susceptible variety) in 2013
(high temperature and strong radiation during the rice reproductive growth
stage), 2012 and 2014 (low temperature and weak radiation during rice
reproductive growth stage). The results showed that the length of the basal
internodes and the height of the gravitational centres were greater in plants
grown in 2014. Dry weight of basal culms, culm diameter, lignin content and total
content of structural carbohydrates (lignin and cellulose) in basal internodes
were reduced in these plants, causing a significant reduction in the bending
stress and lodging resistance of the rice stems. Low-temperature, overcast and
rainy weather had a greater effect on lodging resistance in indica rice compared
with japonica rice. This was reflected in a greater reduction in the lignin
content of the indica rice stems, which yielded a significantly lower breaking
strength and bending stress.
PMID- 28422162
TI - A comparative analysis of human and mouse islet G-protein coupled receptor
expression.
AB - G-protein coupled receptors (GPCRs) are essential for islet function, but most
studies use rodent islets due to limited human islet availability. We have
systematically compared the GPCR mRNA expression in human and mouse islets to
determine to what extent mouse islets can be used as surrogates for human islets
to study islet GPCR function, and we have identified species-specific expression
of several GPCRs. The A3 receptor (ADORA3) was expressed only in mouse islets and
the A3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse
islets, with no effect on human islets. Similarly, mRNAs encoding the galanin
receptors GAL1 (GALR1), GAL2 (GALR2) and GAL3 GALR3) were abundantly expressed in
mouse islets but present only at low levels in human islets, so that it reads
(GALR3) and galanin inhibited insulin secretion only from mouse islets.
Conversely, the sst1 receptor (SSTR1) was abundant only in human islets and its
selective activation by CH 275 inhibited insulin secretion from human islets,
with no effect on mouse islets. Our comprehensive human and mouse islet GPCR
atlas has demonstrated that species differences do exist in islet GPCR expression
and function, which are likely to impact on the translatability of mouse studies
to the human context.
PMID- 28422163
TI - Distorted Immunodominance by Linker Sequences or other Epitopes from a Second
Protein Antigen During Antigen-Processing.
AB - The immune system focuses on and responds to very few representative
immunodominant epitopes from pathogenic insults. However, due to the complexity
of the antigen processing, understanding the parameters that lead to
immunodominance has proved difficult. In an attempt to uncover the determinants
of immunodominance among several dominant epitopes, we utilized a cell free
antigen processing system and allowed the system to identify the hierarchies
among potential determinants. We then tested the results in vivo; in mice and in
human. We report here, that immunodominance of known sequences in a given protein
can change if two or more proteins are being processed and presented
simultaneously. Surprisingly, we find that new spacer/tag sequences commonly
added to proteins for purification purposes can distort the capture of the
physiological immunodominant epitopes. We warn against adding tags and spacers to
candidate vaccines, or recommend cleaving it off before using for vaccination.
PMID- 28422164
TI - On the Role of the Electrical Field in Spark Plasma Sintering of UO2+x.
AB - The electric field has a large effect on the stoichiometry and grain growth of
UO2+x during Spark Plasma Sintering. UO2+x is gradually reduced to UO2.00 as a
function of sintering temperature and time. A gradient in the oxidation state
within the pellets is observed in intermediate conditions. The shape of the
gradient depends unequivocally on the direction of the electrical field. The
positive surface of the pellet shows a higher oxidation state compared to the
negative one. An area with larger grain size is found close to the positive
electrode, but not in contact with it. We interpret these findings with the
redistribution of defects under an electric field, which affect the stoichiometry
of UO2+x and thus the cation diffusivity. The results bear implications for
understanding the electric field assisted sintering of UO2 and non-stoichiometric
oxides in general.
PMID- 28422165
TI - Structural basis of inhibition of lipid-linked oligosaccharide flippase PglK by a
conformational nanobody.
AB - PglK is an ABC transporter that flips a lipid-linked oligosaccharide (LLO) that
serves as a donor in protein N-glycosylation. Previous structures revealed two
inward-facing conformations, both with very large separations of the nucleotide
binding domains (NBDs), and a closed, ADP-bound state that featured an occluded
cavity. To investigate additional states, we developed conformation-sensitive,
single-domain camelid nanobodies (Nb) and studied their effect on PglK activity.
Biochemical, structural, and mass spectrometric analyses revealed that one
inhibitory Nb binds as a single copy to homodimeric PglK. The co-crystal
structure of this Nb and ADP-bound PglK revealed a new, narrowly inward-open
conformation. Rather than inducing asymmetry in the PglK homodimer, the binding
of one Nb results in steric constraints that prevent a second Nb to access the
symmetry-related site in PglK. The Nb performed its inhibitory role by a "sticky
doorstop" mechanism, where inhibition of ATP hydrolysis and LLO flipping activity
occurs due to impaired closing of the NBD interface, which prevents PglK from
converting to an outward-open conformation. This inhibitory mode suggests tight
conformational coupling between the ATPase sites, which may apply to other ABC
transporters.
PMID- 28422166
TI - Identification and characterization of miRNAs in two closely related C4 and C3
species of Cleome by high-throughput sequencing.
AB - Cleome gynandra and Cleome hassleriana, which are C4 and C3 plants, respectively,
are two species of Cleome. The close genetic relationship between C. gynandra and
C. hassleriana provides advantages for discovering the differences in leaf
development and physiological processes between C3 and C4 plants. MicroRNAs
(miRNAs) are a class of important regulators of various biological processes. In
this study, we investigate the differences in the characteristics of miRNAs
between C. gynandra and C. hassleriana using high-throughput sequencing
technology. In total, 94 and 102 known miRNAs were identified in C. gynandra and
C. hassleriana, respectively, of which 3 were specific for C. gynandra and 10
were specific for C. hassleriana. Ninety-one common miRNAs were identified in
both species. In addition, 4 novel miRNAs were detected, including three in C.
gynandra and three in C. hassleriana. Of these miRNAs, 67 were significantly
differentially expressed between these two species and were involved in extensive
biological processes, such as glycol-metabolism and photosynthesis. Our study not
only provided resources for C. gynandra and C. hassleriana research but also
provided useful clues for the understanding of the roles of miRNAs in the
alterations of biological processes in leaf tissues during the evolution of the
C4 pathway.
PMID- 28422167
TI - Biotin-transfer from a trifunctional crosslinker for identification of cell
surface receptors of soluble protein ligands.
AB - Here we describe a novel crosslinker and its application as a biotin-transfer
reagent to identify cell surface receptors of soluble protein ligands on live
cells. This crosslinker contains three functional groups: an aldehyde-reactive
aminooxy group, a sulfhydryl, and a biotin (ASB). It is readily synthesized via a
3-step addition reaction using standard solid-phase peptide synthesis methods and
commercially available intermediates, allowing access to laboratories without
specialized synthetic chemistry capabilities. For the biotin-transfer method, ASB
is linked to a protein ligand through the sulfhydryl group in a two-step process
that allows the introduction of a disulfide bond between the ligand and the
crosslinker. Incubation of the labelled ligand with oxidized live cells leads to
the formation of crosslinks with aldehyde-containing glycans on the cell surface
receptor. Subsequent reduction of the disulfide bond results in biotin transfer
from the ligand to the cell surface receptor. Protein biotinylation that is
mediated by ligand binding to its receptor is differentiated from background
biotinylation events by comparison with a similarly labelled control protein
using comparative proteomic mass spectrometry to quantify streptavidin-bound
proteins. Using this method, we successfully identified the cell surface
receptors of a peptide hormone, a monoclonal antibody, and a single-domain
antibody-Fc fusion construct.
PMID- 28422168
TI - Competitions between prosocial exclusions and punishments in finite populations.
AB - Prosocial punishment has been proved to be a powerful mean to promote
cooperation. Recent studies have found that social exclusion, which indeed can be
regarded as a kind of punishment, can also support cooperation. However, if
prosocial punishment and exclusion are both present, it is still unclear which
strategy is more advantageous to curb free-riders. Here we first study the direct
competition between different types of punishment and exclusion. We find that
pool (peer) exclusion can always outperform pool (peer) punishment both in the
optional and in the compulsory public goods game, no matter whether second-order
sanctioning is considered or not. Furthermore, peer exclusion does better than
pool exclusion both in the optional and in the compulsory game, but the situation
is reversed in the presence of second-order exclusion. Finally, we extend the
competition among all possible sanctioning strategies and find that peer
exclusion can outperform all other strategies in the absence of second-order
exclusion and punishment, while pool exclusion prevails when second-order
sanctioning is possible. Our results demonstrate that exclusion is a more
powerful strategy than punishment for the resolution of social dilemmas.
PMID- 28422169
TI - The role of domestication and experience in 'looking back' towards humans in an
unsolvable task.
AB - A key element thought to have changed during domestication is dogs' propensity to
communicate with humans, particularly their inclination to gaze at them. A
classic test to measure this is the 'unsolvable task', where after repeated
successes in obtaining a reward by object-manipulation, the animal is confronted
with an unsolvable version of the task. 'Looking back' at humans has been
considered an expression of dogs seeking help. While it occurs more in dogs than
in socialized wolves, the level of exposure to human communication also appears
to play a role. We tested similarly raised adult wolves and mixed breed dogs, pet
dogs and free-ranging dogs. Unlike previous studies, as well as species and
levels of socialization, we included 'persistence' in trying to solve the task as
a potential explanatory factor. Wolves were more persistent than all dog groups.
Regardless of socialization or species, less persistent animals looked back
sooner and longer. Free-ranging dogs, despite little exposure to dog-human
communication, behaved similarly to other dogs. Together, results suggest that
basic wolf-dog differences in motivation and exploration may override differences
in human-directed behaviour when animals are equally socialized, and that once
the human is considered a social partner, looking behaviour occurs easily.
PMID- 28422170
TI - Dynamic through-silicon-via filling process using copper electrochemical
deposition at different current densities.
AB - This work demonstrates the dynamic through-silicon-via (TSV) filling process
through staged electrodeposition experiments at different current densities.
Different morphologies corresponding to TSV filling results can be obtained by
controlling the applied current density. Specifically, a low current density (4
mA/cm2) induces seam defect filling, a medium current density (7 mA/cm2) induces
defect-free filling, and a high current density (10 mA/cm2) induces void defect
filling. Analysis of the filling coefficient indicates that the effect of current
density on the TSV filling models is triggered by the coupling effect of
consumption and diffusion of additives and copper ions. Further, the
morphological evolution of plating reveals that the local deposition rate is
affected by the geometrical characteristics of the plating.
PMID- 28422171
TI - Nanoporous Microsphere Assembly of Iodine-Functionalised Silver Nanoparticles as
a Novel Mini-Substrate for Enriching and Sensing.
AB - Herein, debris particulates of nanoporous silver (np-Ag) were synthesised by a
dealloying method, and their integration behaviour and surface-enhanced Raman
scattering (SERS) properties during iodine functionalisation were examined. It
was found that the dealloyed np-Ag debris particulates gradually assembled to
form rigid nanoporous microspheres comprising Ag nano-ligaments due to mechanical
collisions during iodine treatment. High-resolution transmission electron
microscopy and X-ray photoelectron microscopy clearly showed the iodide surface
of np-Ag, which was dotted with iodine or iodide 'nanoislands'. The exceptional,
and unexpected, integration and surface structures result in a highly enhanced
localised surface plasmon resonance. Furthermore, the robust nanoporous
microspheres can be employed individually as as-produced miniaturised electrodes
to electrically enrich target molecules at parts-per-trillion levels, so as to
achieve charge selectivity and superior detectability compared with the ordinary
SERS effect.
PMID- 28422172
TI - Transient elastography as a screening tool for liver fibrosis in a large
hemodialysis population.
AB - Metabolic syndrome, an etiological factor in non-alcoholic fatty liver disease
(NAFLD), is often present in hemodialysis patients. Little is known about the
prevalence of, and factors associated with, liver fibrosis in hemodialysis
populations. We used transient elastography (TE) to investigate these phenomena.
659 patients treated with chronic hemodialysis were enrolled. We excluded those
with excess alcohol intake, liver stiffness measurement (LSM) failure, or
unreliable LSM values. LSM >=8.0 kPa was used as a cutoff suggesting clinically
relevant fibrosis. Controlled attenuation parameter (CAP) >= 232.5 dB/m was used
as a cutoff suggesting steatosis. 333 patients (50.5%) had steatosis, 159 (24.1%)
had hepatitis B or C, and 149 (22.6%) had LSM >=8.0 kPa. In multivariable
analyses, male gender (OR: 2.16; 95% CI: 1.29-3.63; P = 0.004), overweight body
habitus (OR:2.31; 95% CI: 1.35-3.94; P = 0.002), high AST level (OR:1.08; 95% CI:
1.04-1.12; P < 0.001), low albumin level (OR: 0.25; 95% CI: 0.12-0.53; P <
0.001), low creatinine level (OR: 0.89; 95% CI: 0.79-1.00; P = 0.05) and low
platelet count (OR: 0.99; 95% CI: 0.99-1.00; P < 0.001) were associated with LSM
>=8.0 kPa. We thus conclude that hemodialysis patients have a high prevalence of
NAFLD and clinically relevant fibrosis. NAFLD may be an important determinant of
clinically relevant fibrosis in hemodialysis populations.
PMID- 28422173
TI - Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular
similarity between Mowat-Wilson syndrome and Ehlers-Danlos syndrome.
AB - Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo
heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS
patients show multiple anomalies including intellectual disability, a distinctive
facial appearance, microcephaly, congenital heart defects and Hirschsprung
disease. However, the skin manifestation(s) of patients with MOWS has not been
documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers
Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic
scars and joint hypermobility. MOWS patients showed a thinner dermal thickness
and electron microscopy revealed miniaturized collagen fibrils. Notably, mice
with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated
redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to
those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a
decreased expression of extracellular matrix (ECM) molecules, such as collagens,
whereas molecules involved in degradation of the ECM, such as matrix
metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin
fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit
an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to
ZEB2 mutations or deletions.
PMID- 28422174
TI - High expression of matrix metalloproteinases 16 is associated with the aggressive
malignant behavior and poor survival outcome in colorectal carcinoma.
AB - Recent evidence suggested an important role of matrix metalloproteinases 16
(MMP16) in the progression of several cancers. However, the contribution of MMP16
to colorectal cancer (CRC) remains elusive. In this study, we combined analyzed
the MMP16 expression in The Cancer Genome Atlas (TCGA), GSE39582 database and in
house database. In TCGA and GSE39584 database, the log-rank test demonstrated
that overall survival (OS) for patients with low MMP16 expression in tumor
tissues was significantly higher than those with high expression (P < 0.05). In
the validation cohort, high MMP16 expression was significantly correlated with N
stage (P = 0.008) and lymphovascular invasion (P = 0.002). The 5-year OS and
disease free survival (DFS) in high and low MMP16 expression groups were 66.0%
and 80.6%, 54.3% and 72.8%, respectively. Univariate and multivariate analysis
showed that high MMP16 expression was an independently prognosis factor for both
OS and DFS (P < 0.05). Functional study found that silencing MMP16 expression
could inhibit migration and invasion of colon cancer cells. In conclusion, high
expression of MMP16 is associated with the aggressive malignant behavior and poor
survival outcome of CRC patients. MMP16 can serve as an indicator of prognosis as
well as a potential novel target for treatment of CRC patients.
PMID- 28422175
TI - Assessment of China's H5N1 routine vaccination strategy.
AB - In this study, a simulation model was used to assess the epidemiological and
economic impacts of the routine vaccination strategy for H5N1 in China at the
national level. The results of the simulation show that a routine vaccination
strategy at the national level could have a substantial impact on decreasing H5N1
outbreaks; it could therefore markedly reduce the severity and duration of an
H5N1 epidemic at the national level in China. Under a routine vaccination
programme, when a flock is infected, the number of depopulated birds could be
reduced by approximately 91%, the outbreak duration could be reduced by one
fourth, and the probability of an H5N1 outbreak could be reduced to 51.5%.
Although the use of vaccination has obvious benefits, if indirect costs were not
considered, the mean direct cost of simulated disease control without vaccination
was only 1.36% of the cost of the routine vaccination strategy, and this former
approach would have saved 57 billion yuan for all poultry in China from 2004 to
2012. Traditional H5N1 control strategies with culling programmes at the national
level represented a better choice for China.
PMID- 28422177
TI - Microbiota: Diet can protect against type 1 diabetes.
PMID- 28422176
TI - The characteristics of newly diagnosed adult early-onset diabetes: a population
based cross-sectional study.
AB - To investigate the characteristics of newly diagnosed early-onset diabetes in the
Chinese population, 2801 newly diagnosed diabetes participants without known
diabetes or pre-diabetes in a national cross-sectional survey were analysed.
Participants were divided into quartiles (22-43, 44-52, 53-61 and >61 years)
according to age of diabetes onset and the first group were defined as early
onset diabetes group. Early-onset diabetes group had lower systolic blood
pressure (SBP), total cholesterol, low density lipoprotein cholesterol, 2-hour
post prandial blood glucose and urine albumin creatinine ratio. There was no
difference in body mass index, Homeostasis model assessment (HOMA) of beta cell
function and diabetes family history between early-onset diabetes participants
and any other age groups. HOMA of insulin resistance (IR) scores and disposition
index 30 minutes after glucose load (DI30) were increased in early-onset diabetes
participants. The beta cell function declination was more deteriorated in early
onset diabetes participants. Male gender, triglycerides, HOMA-IR and DI30 were
positively associated with an earlier age at diagnosis. In conclusion, patients
diagnosed with diabetes at a younger age are characterized by a similar
cardiovascular risk profile with increased insulin resistance and more severe
beta cell failure than patients diagnosed at a later age.
PMID- 28422178
TI - Enhancing protective immunity to malaria with a highly immunogenic virus-like
particle vaccine.
AB - The leading malaria vaccine in development is the circumsporozoite protein (CSP)
based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of
Plasmodium falciparum infection. It induces modest levels of protective efficacy,
thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance
vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and
therefore developed a next-generation RTS,S-like vaccine, called R21. The major
improvement is that in contrast to RTS,S, R21 particles are formed from a single
CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a
vaccine composed of a much higher proportion of CSP than in RTS,S. We demonstrate
that in BALB/c mice R21 is immunogenic at very low doses and when administered
with the adjuvants Abisco-100 and Matrix-M it elicits sterile protection against
transgenic sporozoite challenge. Concurrent induction of potent cellular and
humoral immune responses was also achieved by combining R21 with TRAP-based viral
vectors and protective efficacy was significantly enhanced. In addition, in
contrast to RTS,S, only a minimal antibody response to the HBsAg carrier was
induced. These studies identify an anti-sporozoite vaccine component that may
improve upon the current leading malaria vaccine RTS,S. R21 is now under
evaluation in Phase 1/2a clinical trials.
PMID- 28422179
TI - Heritability maps of human face morphology through large-scale automated three
dimensional phenotyping.
AB - The human face is a complex trait under strong genetic control, as evidenced by
the striking visual similarity between twins. Nevertheless, heritability
estimates of facial traits have often been surprisingly low or difficult to
replicate. Furthermore, the construction of facial phenotypes that correspond to
naturally perceived facial features remains largely a mystery. We present here a
large-scale heritability study of face geometry that aims to address these
issues. High-resolution, three-dimensional facial models have been acquired on a
cohort of 952 twins recruited from the TwinsUK registry, and processed through a
novel landmarking workflow, GESSA (Geodesic Ensemble Surface Sampling Algorithm).
The algorithm places thousands of landmarks throughout the facial surface and
automatically establishes point-wise correspondence across faces. These landmarks
enabled us to intuitively characterize facial geometry at a fine level of detail
through curvature measurements, yielding accurate heritability maps of the human
face (www.heritabilitymaps.info).
PMID- 28422180
TI - Patterning Graphene Film by Magnetic-assisted UV Ozonation.
AB - Developing an alternative method for fabricating microscale graphene patterns
that overcomes the obstacles of organic contamination, linewidth resolution, and
substrate damaging is paramount for applications in optoelectronics. Here we
propose to pattern chemical vapor deposition grown graphene film through a
stencil mask by magnetic-assisted ultraviolet (UV) ozonation under irradiation of
a xenon excimer lamp. In this process, the paramagnetic oxygen molecules and
photochemically generated oxygen radicals are magnetized and attracted in an
inhomogenous external magnetic field. As a consequence, their random motions
convert into directional, which can greatly modify or enhance the quality of
graphene patterns. Using a ferromagnetic steel mask, an approximately vertical
magnetic-field-assisted UV ozonation (BZ = 0.31 T, ?BZ = 90 T . m-1) has a
capability of patterning graphene microstructures with a line width of 29 MUm and
lateral under-oxidation less than 4 MUm. Our approach is applicable to patterning
graphene field-effect transistor arrays, and it can be a promising solution
toward resist-free, substrate non-damaging, and cost effective microscale
patterning of graphene film.
PMID- 28422181
TI - Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and
their major contributed antioxidant compounds.
AB - The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea
were evaluated, and their major antioxidant compounds contributed to the total
amount of synergy were determined. The antioxidant compounds in O. fragrans
flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The
synergistic antioxidant interactions between O. fragrans flowers with green tea
and their antioxidant compounds were tested using the Prieto's model after the
simulated digestion. The main antioxidant compounds in O. fragrans flowers were
acteoside and salideroside, whereas the main antioxidant compounds in green tea
were caffeine, gallic acid, and L-epicatechin. The significant synergistic effect
between O. fragrans flowers and green tea was observed and among nearly all of
the combinations of their antioxidant compounds. Among the combinations,
acteoside and gallic acid contributed most to the antioxidant synergy between O.
fragrans flowers and green tea. However, the simulated digestion decreased this
antioxidant synergy because it reduced the contents and the antioxidant
capacities of their compounds, as well as the antioxidant synergy among the
compounds.
PMID- 28422182
TI - Carbon nanotube/metal-sulfide composite flexible electrodes for high-performance
quantum dot-sensitized solar cells and supercapacitors.
AB - Carbon nanotubes (CNT) and metal sulfides have attracted considerable attention
owing to their outstanding properties and multiple application areas, such as
electrochemical energy conversion and energy storage. Here we describes a cost
effective and facile solution approach to the preparation of metal sulfides (PbS,
CuS, CoS, and NiS) grown directly on CNTs, such as CNT/PbS, CNT/CuS, CNT/CoS, and
CNT/NiS flexible electrodes for quantum dot-sensitized solar cells (QDSSCs) and
supercapacitors (SCs). X-ray photoelectron spectroscopy, X-ray diffraction, and
transmission electron microscopy confirmed that the CNT network was covered with
high-purity metal sulfide compounds. QDSSCs equipped with the CNT/NiS counter
electrode (CE) showed an impressive energy conversion efficiency (eta) of 6.41%
and remarkable stability. Interestingly, the assembled symmetric CNT/NiS-based
polysulfide SC device exhibited a maximal energy density of 35.39 W h kg-1 and
superior cycling durability with 98.39% retention after 1,000 cycles compared to
the other CNT/metal-sulfides. The elevated performance of the composites was
attributed mainly to the good conductivity, high surface area with mesoporous
structures and stability of the CNTs and the high electrocatalytic activity of
the metal sulfides. Overall, the designed composite CNT/metal-sulfide electrodes
offer an important guideline for the development of next level energy conversion
and energy storage devices.
PMID- 28422183
TI - Enhanced superconductivity accompanying a Lifshitz transition in electron-doped
FeSe monolayer.
AB - The origin of enhanced superconductivity over 50 K in the recently discovered
FeSe monolayer films grown on SrTiO3 (STO), as compared to 8 K in bulk FeSe, is
intensely debated. As with the ferrochalcogenides AxFe2-ySe2 and potassium-doped
FeSe, which also have a relatively high-superconducting critical temperature
(Tc), the Fermi surface (FS) of the FeSe/STO monolayer films is free of hole-like
FS, suggesting that a Lifshitz transition by which these hole FSs vanish may help
increasing Tc. However, the fundamental reasons explaining this increase of Tc
remain unclear. Here we report a 15 K jump of Tc accompanying a second Lifshitz
transition characterized by the emergence of an electron pocket at the Brillouin
zone centre, which is triggered by high-electron doping following in situ
deposition of potassium on FeSe/STO monolayer films. Our results suggest that the
pairing interactions are orbital dependent in generating enhanced
superconductivity in FeSe.
PMID- 28422184
TI - Sea-level proxies in Holocene raised beach ridge deposits (Greenland) revealed by
ground-penetrating radar.
AB - Identification of sea-level proxies is important for reconstruction of past sea
level variation. Methods for reconstructing Holocene relative sea-level curves
are crucial for quantification of the impact of Greenland ice thickness variation
on global sea level and vertical land movement. Arctic beach ridges constitute
important potential archives of sea-level variation. However, their surface
morphology may have undergone modification since deposition due to
freezing/thawing processes and erosion, and their morphology may therefore not be
trustworthy for sea-level reconstruction. Therefore, geophysical imaging is used
to examine the internal structures of the beach ridges and to define a sea-level
proxy unaffected by surface processes. The GPR reflections from study sites in
West and South Greenland show deposition of beachface deposits and upper
shoreface deposits; the contact between steeply dipping beachface reflections and
less-dipping shoreface reflections is used as sea-level proxy. Numerous points
are identified along GPR transects facilitating reconstruction of relative sea
level variation of hitherto unprecedented resolution. Erosional events and
deformation caused by freezing/thawing processes are clearly delineated. The
approach constitutes a solid base for reconstruction of relative sea-level curves
affected by a well-defined vertical land movement history since the studied beach
ridge systems represent long time intervals and only relatively small spatial
extents.
PMID- 28422185
TI - Improved ganoderic acids production in Ganoderma lucidum by wood decaying
components.
AB - Ganoderma lucidum is a legendary Traditional Chinese Medicine (TCM) over a few
thousands of years and one kind of its major active components are Ganoderic
acids (GAs). GAs are largely produced in the mushroom primordium and fruiting
body but much less in mycelium stage. However, little is known on the underlying
regulatory mechanism. As a saprophytic fungus, G. lucidum solely obtains
nutrients by wood decaying. Wood in general contains sophisticated chemical
components with diverse structural units. To explore a strategy that extensively
leads to GAs induction in the submerged liquid fermentation, all chemical
components that might be possibly from the wood decaying were tested individually
as GAs inducers. It was found that GAs production increased 85.96% by 1.5%
microcrystalline cellulose (MCC) and 63.90% by 0.5% D-galactose. The
transcription level of a few rate-limiting or chemically diverting enzymes
responsible for GAs biosynthesis was greatly induced by MCC and D-galactose. The
concentration and time-course titration study indicated that these two chemicals
might not be utilized as carbon sources but they played a comprehensive role in
the secondary metabolites synthesis. Our data indicated that MCC and D-galactose
might be further industrialized for higher GAs production in G. lucidum in
submerged fermentation.
PMID- 28422186
TI - High-fat diet induces systemic B-cell repertoire changes associated with insulin
resistance.
AB - The development of obesity-associated insulin resistance is associated with B
lymphocyte accumulation in visceral adipose tissue (VAT) and is prevented by B
cell ablation. To characterize potentially pathogenic B-cell repertoires in this
disorder, we performed high-throughput immunoglobulin (Ig) sequencing from
multiple tissues of mice fed high-fat diet (HFD) and regular diet (RD). HFD
significantly changed the biochemical properties of Ig heavy-chain
complementarity-determining region-3 (CDRH3) sequences, selecting for IgA
antibodies with shorter and more hydrophobic CDRH3 in multiple tissues. A set of
convergent antibodies of highly similar sequences found in the VAT of HFD mice
but not RD mice showed significant somatic mutation, suggesting a response shared
between mice to a common antigen or antigens. These findings indicate that a
simple high-fat dietary intervention has a major impact on mouse B-cell
repertoires, particularly in adipose tissues.
PMID- 28422187
TI - A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue
reactivation and hypersensitivity in the lung.
AB - Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell
rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification
for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1)
regulates key mechanisms underlying lymphoid tissue biology and its chemical
modulation causes lymphocyte retention in lymph nodes. Given the putative
immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated
whether or not chemical modulation of S1P1 caused lymphocyte retention within
TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically
to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity
pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by
S1P1-positive microvessels. Upon MSS rechallenge, the S1P1 agonist RP001
prevented the pulmonary increase of CXCL13, a chief regulator of B-cell
recruitment in lymphoid tissues. This was associated with a complete inhibition
of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS
specific antibody titers in the lung. Interference with TLT reactivation was
associated with a 77% reduction of neutrophil accumulation and with full
inhibition of protein-rich leakage in the airways. Thus, an S1P1 agonist hinders
TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic
features of experimental hypersensitivity pneumonitis.
PMID- 28422188
TI - Resolvin D1 enhances the resolution of lung inflammation caused by long-term
Pseudomonas aeruginosa infection.
AB - Pseudomonas aeruginosa lung infection is a main cause of disability and mortality
worldwide. Acute inflammation and its timely resolution are crucial for ensuring
bacterial clearance and limiting tissue damage. Here, we investigated protective
actions of resolvin (Rv) D1 in lung infection induced by the RP73 clinical strain
of P. aeruginosa. RvD1 significantly diminished bacterial growth and neutrophil
infiltration during acute pneumonia caused by RP73. Inoculum of RP73, immobilized
in agar beads, resulted in persistent lung infection up to 21 days, leading to a
non resolving inflammation reminiscent of human pathology. RvD1 significantly
reduced bacterial titer, leukocyte infiltration, and lung tissue damage. In
murine lung macrophages sorted during P. aeruginosa chronic infection, RvD1
regulated the expression of Toll-like receptors, downstream genes, and microRNA
(miR)-21 and 155, resulting in reduced inflammatory signaling. In vitro, RvD1
enhanced phagocytosis of P. aeruginosa by neutrophils and macrophages,
recapitulating its in vivo actions. These results unveil protective functions and
mechanisms of action of RvD1 in acute and chronic P. aeruginosa pneumonia,
providing evidence for its potent pro-resolution and tissue protective properties
on airway mucosal tissue during infection.
PMID- 28422189
TI - Exome Analysis of Rare and Common Variants within the NOD Signaling Pathway.
AB - Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder.
This study looks at the burden of common and rare coding mutations within 41
genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106
control samples underwent whole-exome sequencing. We compared the burden of
common, rare and private mutation between these two groups using the SKAT-O test.
An independent replication cohort of 33 cases and 111 controls was used to
validate significant findings. We observed variation in 40 of 41 genes comprising
the NOD signaling pathway. Four genes were significantly associated with disease
in the discovery cohort (BIRC2 p = 0.004, NFKB1 p = 0.005, NOD2 p = 0.029 and
SUGT1 p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041)
and NOD2 (p = 0.045) in an independent validation cohort. A gene based test on
the combined discovery and replication cohort confirmed association for BIRC2 (p
= 0.030). We successfully applied burden of mutation testing that jointly
assesses common and rare variants, identifying two previously implicated genes
(NFKB1 and NOD2) and confirmed a possible role in disease risk in a previously
unreported gene (BIRC2). The identification of this novel gene provides a wider
role for the inhibitor of apoptosis gene family in IBD pathogenesis.
PMID- 28422190
TI - Current carried by the Slc26 family member prestin does not flow through the
transporter pathway.
AB - Prestin in the lateral membrane of outer hair cells, is responsible for
electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin's
voltage sensitivity is influenced by intracellular chloride. A regulator of
intracellular chloride is a stretch-sensitive, non-selective conductance within
the lateral membrane, GmetL. We determine that prestin itself possesses a stretch
sensitive, non-selective conductance that is largest in the presence of
thiocyanate ions. This conductance is independent of the anion transporter
mechanism. Prestin has been modeled, based on structural data from related anion
transporters (SLC26Dg and UraA), to have a 7 + 7 inverted repeat structure with
anion transport initiated by chloride binding at the intracellular cleft.
Mutation of residues that bind intracellular chloride, and salicylate treatment
which prevents chloride binding, have no effect on thiocyanate conductance. In
contrast, other mutations reduce the conductance while preserving NLC. When
superimposed on prestin's structure, the location of these mutations indicates
that the ion permeation pathway lies between the core and gate ring of helices,
distinct from the transporter pathway. The uncoupled current is reminiscent of an
omega current in voltage-gated ion channels. We suggest that prestin itself is
the main regulator of intracellular chloride concentration via a route distinct
from its transporter pathway.
PMID- 28422191
TI - Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification
and treatment.
AB - Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic
malignancies in which blasts show markers of multiple developmental lineages and
cannot be clearly classified as acute myeloid or lymphoblastic leukemias.
Historically, various names and classifications were used for this rare entity
accounting for 2-5% of all acute leukemias depending on the diagnostic criterias
used. The currently valid classification of myeloid neoplasms and acute leukemia
published by the World Health Organization (WHO) in 2016 refers to this group of
diseases as MPAL. Because adverse cytogenetic abnormalities are frequently
present, MPAL is generally considered a disease with a poor prognosis. Knowledge
of its treatment is limited to retrospective analyses of small patient cohorts.
So far, no treatment recommendations verified by prospective studies have been
published. The reported data suggest that induction therapy for acute
lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation
is more effective than induction therapy for acute myeloid leukemia or
consolidation chemotherapy. The establishment of cooperative groups and
international registries based on the recent WHO criterias are required to ensure
further progress in understanding and treatment of MPAL. This review summarizes
current knowledge on the diagnosis, classification, prognosis and treatment of
MPAL patients.
PMID- 28422192
TI - Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic
cleft lip with or without cleft palate risk in the Slovak population.
AB - BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the
most common orofacial birth defect with an aetiology involving both genetic and
environmental factors. Genome-wide association studies (GWAS) have identified
several genomic susceptibility regions for nsCL/P. In the present study, the
three well established single nucleotide polymorphisms (SNPs) identified by GWAS
(rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP
identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were
analysed for an association with nsCL/P in Slovak population. METHODS: Nucleotide
variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All
variants of interest were genotyped using high-resolution melting analysis after
real-time PCR. RESULTS: We found significant differences between patient and
control groups with respect to the allele and genotype frequencies for the SNPs
at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward
association with nsCL/P risk. CONCLUSIONS: The results suggest that SNPs at the
1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.
PMID- 28422193
TI - Challenges in developing direct carbon fuel cells.
AB - A direct carbon fuel cell (DCFC) can produce electricity with both superior
electrical efficiency and fuel utilisation compared to all other types of fuel
cells. Although the first DCFC prototype was proposed in 1896, there was, until
the 1970s, little sustained effort to investigate further, because of technology
development issues. Interest in DCFCs has recently been reinvigorated as a
possible method of replacing conventional coal-fired power plants to meet the
demands for lower CO2 emissions, and indeed for efficient utilisation of waste
derived chars. In this article, recent developments in direct carbon conversion
are reviewed, with the principal emphasis on the materials involved. The
development of electrolytes, anodes and cathodes as well as fuel sources is
examined. The activity and chemical stability of the anode materials are a
critical concern addressed in the development of new materials. Redox media of
molten carbonate or molten metal facilitating the transportation of ions offer
promising possibilities for carbon oxidation. The suitability of different carbon
fuels in various DCFC systems, in terms of crystal structure, surface properties,
impurities and particle size, is also discussed. We explore the influence of a
variety of parameters on the electrochemical performance of DCFCs, with regard to
their open circuit voltage, power output and lifetime. The challenges faced in
developing DCFCs are summarised, and potential prospects of the system are
outlined.
PMID- 28422194
TI - Field induced anomalous spreading, oscillation, ejection, spinning, and breaking
of oil droplets on a strongly slipping water surface.
AB - Application of an electric field on an oil droplet floating on the surface of a
deionized water bath showed interesting motions such as spreading, oscillation,
and ejection. The electric field was generated by connecting a pointed platinum
cathode at the top of the oil droplet and a copper anode coated with polymer at
the bottom of the water layer. The experimental setup mimicked a conventional
electrowetting setup with the exception that the oil was spread on a soft and
deformable water isolator. While at relatively lower field intensities we
observed spreading of the droplet, at intermediate field intensities the droplet
oscillated around the platinum cathode, before ejecting out at a speed as high as
~5 body lengths per second at even stronger field intensities. The experiments
suggested that when the electric field was ramped up abruptly to a particular
voltage, any of the spreading, oscillation, or ejection motions of the droplet
could be engendered at lower, intermediate and higher field intensities,
respectively. However, when the field was ramped up progressively by increasing
by a definite amount of voltage per unit time, all three aforementioned motions
could be generated simultaneously with the increase in the field intensity.
Interestingly, when the aforementioned setup was placed on a magnet, the droplet
showed a rotational motion under the influence of the Lorentz force, which was
generated because of the coupling of the weak leakage current with the externally
applied magnetic field. The spreading, oscillation, ejection, and rotation of the
droplet were found to be functions of the oil-water interfacial tension,
viscosity, and size of the oil droplet. We developed simple theoretical models to
explain the experimental results obtained. Importantly, rotating at a higher
speed broke the droplet into a number of smaller ones, owing to the combined
influence of the spreading due to the centripetal force and the shear at the oil
water interface. While the oscillatory and rotational motions of the
incompressible droplet could be employed as stirrers or impellers inside
microfluidic devices for mixing applications, the droplet ejection could be
employed for futuristic applications such as payload transport or drug delivery.
PMID- 28422195
TI - Inducible epitope imprinting: 'generating' the required binding site in membrane
receptors for targeted drug delivery.
AB - We report an inducible epitope imprinting strategy that as a template, a flexible
peptide chain can have a disordered-to-ordered conformational change by suitable
inducement through a molecular imprinting procedure, and the formed nanoparticles
can, in turn, remold the original peptide into the expected conformation and
specifically bind to the corresponding protein.
PMID- 28422196
TI - Boundary layer friction of solvate ionic liquids as a function of potential.
AB - Atomic force microscopy (AFM) has been used to investigate the potential
dependent boundary layer friction at solvate ionic liquid (SIL)-highly ordered
pyrolytic graphite (HOPG) and SIL-Au(111) interfaces. Friction trace and retrace
loops of lithium tetraglyme bis(trifluoromethylsulfonyl)amide (Li(G4) TFSI) at
HOPG present clearer stick-slip events at negative potentials than at positive
potentials, indicating that a Li+ cation layer adsorbed to the HOPG lattice at
negative potentials which enhances stick-slip events. The boundary layer friction
data for Li(G4) TFSI shows that at HOPG, friction forces at all potentials are
low. The TFSI- anion rich boundary layer at positive potentials is more
lubricating than the Li+ cation rich boundary layer at negative potentials. These
results suggest that boundary layers at all potentials are smooth and energy is
predominantly dissipated via stick-slip events. In contrast, friction at Au(111)
for Li(G4) TFSI is significantly higher at positive potentials than at negative
potentials, which is comparable to that at HOPG at the same potential. The
similarity of boundary layer friction at negatively charged HOPG and Au(111)
surfaces indicates that the boundary layer compositions are similar and rich in
Li+ cations for both surfaces at negative potentials. However, at Au(111), the
TFSI- rich boundary layer is less lubricating than the Li+ rich boundary layer,
which implies that anion reorientations rather than stick-slip events are the
predominant energy dissipation pathways. This is confirmed by the boundary
friction of Li(G4) NO3 at Au(111), which shows similar friction to Li(G4) TFSI at
negative potentials due to the same cation rich boundary layer composition, but
even higher friction at positive potentials, due to higher energy dissipation in
the NO3- rich boundary layer.
PMID- 28422197
TI - Coupling graphene nanomechanical motion to a single-electron transistor.
AB - Graphene-based electromechanical resonators have attracted great interest
recently because of the outstanding mechanical and electrical properties of
graphene and their various applications. However, the coupling between mechanical
motion and charge transport has not been explored in graphene. Herein, we studied
the mechanical properties of a suspended 50 nm wide graphene nanoribbon, which
also acts as a single-electron transistor (SET) at low temperatures. Using the
SET as a sensitive detector, we found that the resonance frequency could be tuned
from 82 MHz to 100 MHz and the quality factor exceeded 30 000. The strong charge
mechanical coupling was demonstrated by observing the SET induced ~140 kHz
resonance frequency shifts and mechanical damping. We also found that the SET can
enhance the nonlinearity of the resonator. Our SET-coupled graphene mechanical
resonator could approach an ultra-sensitive mass resolution of ~0.55 * 10-21 g
and a force sensitivity of ~1.9 * 10-19 N (Hz)-1/2, and can be further improved.
These properties indicate that our device is a good platform for both fundamental
physical studies and potential applications.
PMID- 28422198
TI - Multiplexed gene silencing in living cells and in vivo using a DNAzymes-CoOOH
nanocomposite.
AB - We demonstrate a novel DNAzymes-based nanocomposite that can simultaneously
silence three types of genes in living cells and in vivo. The synergetic strategy
for silencing three different genes can significantly enhance the knockdown
efficacy and effectively inhibit the cancer cells' progression.
PMID- 28422199
TI - Hybridization chain reactions on silica coated Qbeads for the colorimetric
detection of multiplex microRNAs.
AB - A robust Qbead platform that integrated with target-binding, hybridization chain
reaction and staining was developed for the direct multiplexed detection of
endogenous miRNAs by amplified Qbead-colour change.
PMID- 28422200
TI - Enhancing MRI of liver metastases with a zwitterionized biodegradable dendritic
contrast agent.
AB - Metastasis is the main reason for cancer-associated mortality, and accurate
diagnostic imaging of metastases is critical for the clinical administration and
tailoring personalized treatments for metastatic tumors. However, magnetic
resonance imaging of metastases in the liver is impeded by its low sensitivity
because the currently used contrast agents accumulate in hepatocytes and Kupffer
cells instead of cancer cells. Herein, a 4th generation zwitterionized
biodegradable dendritic contrast agent (DCA) with a size of ca. 9 nm and a
longitudinal relaxivity of 15.7 mM-1 s-1 in terms of Gd was synthesized and used
to enhance the MRI of liver metastasis. The DCA could remarkably enhance the MRI
of metastasized tumors in the liver, because it could simultaneously reduce the
background signal in the liver by avoiding uptake by hepatocytes and Kupffer
cells through the zwitterionization and increase the signal in tumors through the
enhanced permeability and retention effect. Moreover, in contrast to non
biodegradable DCA, this DCA showed minimal long-term Gd3+ retention in all organs
and tissues because it could be degraded into small fragments. The significant
capability of enhancing the MRI of metastases in the liver plus its excellent
biodegradability made this DCA a promising CA for metastatic tumor imaging.
PMID- 28422201
TI - Self-exothermic reaction prompted synthesis of single-layered graphene quantum
dots at room temperature.
AB - The easy fabrication of single-layered graphene quantum dots (s-GQDs) still faces
challenge. Herein, we report an efficient route to fabricate s-GQDs within 5 min
at room temperature by introducing a simple self-exothermic reaction. The as
prepared s-GQDs can specifically bind with aluminium ions to produce an
aggregation-induced emission enhancement effect.
PMID- 28422202
TI - Efficient phosphine-mediated formal C(sp3)-C(sp3) coupling reactions of alkyl
halides in batch and flow.
AB - The construction of C(sp3)-C(sp3) bond is an essential chemical transformation in
synthetic chemistry due to its abundance in organic scaffolds. Here we
demonstrate a valuable adaptation of the Wittig-type chemical procedure to
efficiently facilitate C(sp3)-C(sp3) bond formation utilizing a range of alkyl
building blocks. Additionally the method is amenable with flow synthesis to
afford coupled products in good to excellent yields without laborious
purification process.
PMID- 28422203
TI - A nanoporous Ag(i) coordination polymer for selective adsorption of carcinogenic
dye Acid Red 26.
AB - A cationic Ag(i) coordination polymer with 1D nanoporous channels (ca. 1.22 nm
diameter) shows the selective and complete removal of carcinogenic dye Acid Red
26 from aqueous solution upon the size-exclusion and charge-matching effect.
PMID- 28422204
TI - Interface modulation of bacteriogenic Ag/AgCl nanoparticles by boosting the
catalytic activity for reduction reactions using Co2+ ions.
AB - Boosting the low catalytic activity of bacteriogenic Ag/AgCl nanoparticles (NPs)
by adding Co2+ in a model reaction, i.e. p-nitrophenol (PNP) reduction, was
observed. Under optimal conditions, Co-Ag/AgCl NPs show an apparent rate constant
(kapp) of 0.0837 s-1 upon PNP reduction. Considering the trace amount of Co
Ag/AgCl NPs used in catalysis (about 1.2 MUg), the activity parameter kappa
(which is the ratio of kapp and catalyst mass) can reach more than 6.97 * 104 s-1
g-1, which is 214-fold higher than that of pristine Ag/AgCl NPs. Meanwhile, this
kappa value is also the highest value reported to date. In addition, the biogenic
Co-Ag/AgCl NPs exhibit superior catalytic activities over other substrates, such
as m-nitrophenol, o-nitrophenol, methyl orange and rhodamine B. The activity
enhancement mechanism is supposed to be that Co2+ acts as a Lewis acid, and
coordinates with the surface peptides to affect the electric field distribution
at the Ag/AgCl NP interface.
PMID- 28422205
TI - A general strategy for the in situ decoration of porous Mn-Co bi-metal oxides on
metal mesh/foam for high performance de-NOx monolith catalysts.
AB - Owing to their advantages of strong mechanical stability, plasticity, thermal
conductivity and mass transfer ability, metal foam or meshes are considered
promising monolith supports for de-NOx application. In this work, we developed a
facile method for the decoration of porous Mn-Co bi-metal oxides on Fe meshes.
The block-like structure was derived from in situ coating, and simultaneous
nucleation and growth of the Mn-Co hydroxide precursor, while the porous Mn-Co
oxides were formed via the calcination process. Moreover, the decoration of the
high-purity Co2MnO4 spinel could lead to enhanced reducibility and adsorption
behaviors, which are crucial to the catalytic process. Of note is the fact that
the Fe mesh used in the synthesis procedure could be substituted by various metal
supports including Ti mesh, Cu foam and Ni foam. Driven by the above motivations,
metal supports decorated with Mn-Co oxides were evaluated as monolith de-NOx
catalysts for the first time. Inspiringly, these catalysts demonstrate
outstanding low-temperature catalytic activity, desirable stability and excellent
H2O resistance. This work might open up a new path for the design and development
of high performance de-NOx monolith catalysts.
PMID- 28422206
TI - Cage-like B39+ clusters with the bonding pattern of sigma + pi double
delocalization: new members of the borospherene family.
AB - The recently observed cage-like borospherenes D2d B40-/0 and C3/C2 B39- have
attracted considerable attention in chemistry and materials science. Based on
extensive global minimum searches and first-principles theory calculations, we
present herein the possibility of cage-like Cs B39+ (1) and Cs B39+ (2) which
possess five hexagonal and heptagonal faces and one filled hexagon and follow the
bonding pattern of sigma + pi double delocalization with 12 delocalized pi bonds
over a sigma-skeleton, adding two new members to the borospherene family. IR,
Raman, and UV-vis spectra of Cs B39+ (1) and Cs B39+ (2) are computationally
simulated to facilitate their experimental characterization.
PMID- 28422207
TI - Oxygen thermomigration in acceptor-doped perovskite.
AB - The recent proposal of possible oxygen-thermomigration as a plausible mechanism
for unipolar resistive switching of oxide memristors is now widely employed in
modelling or simulating their memristive function on the grounds of the
conventional picture that the mobile component O is always thermophobic, with its
reduced heat-of-transport being equal to its migrational enthalpy (qO* = DeltaHm
> 0). At 1000 degrees C, we measured the thermomigration of mobile-component O
in a prototype memristive perovskite, CaTi0.90Sc0.10O2.95+delta, across its near
stoichiometric regime (delta ~ 0), where oxygen vacancy concentration is
essentially fixed by doping acceptor impurities (i.e., ). It has been found that
the reduced heat-of-transport of mobile O (qO*) varies systematically in the
range of -2 < qO*/eV <= +2, as the composition varies from hypo-(delta < 0) to
hyper-stoichiometry (delta > 0), exhibiting a sign reversal or thermomigration
direction change from thermophilic (qO* < 0) to thermophobic (qO* > 0). This sign
reversal is attributed to the change in the electronic ambipolar company of from
electrons to holes crossing the stoichiometric composition delta = 0. The
numerical data for qO* together with the measurement details are reported.
PMID- 28422208
TI - Encapsulation into complex coacervate core micelles promotes EGFP dimerization.
AB - Complex coacervate core micelles (C3Ms) are colloidal structures useful for
encapsulation of biomacromolecules. We previously demonstrated that enhanced
green fluorescent protein (EGFP) can be encapsulated into C3Ms using the diblock
copolymer poly(2-methyl-vinyl-pyridinium)41-b-poly(ethylene-oxide)205. This
packaging resulted in deviating spectroscopic features of the encapsulated EGFP
molecules. Here we show that for monomeric EGFP variant (mEGFP) micellar
encapsulation affects the absorption and fluorescence properties to a much lesser
extent, and that changes in circular dichroism characteristics are specific for
encapsulated EGFP. Time-resolved fluorescence anisotropy of encapsulated (m)EGFP
established the occurrence of homo-FRET (Forster resonance energy transfer) with
larger transfer correlation times in the case of EGFP. Together, these findings
support that EGFP dimerizes whereas the mEGFP mainly remains as a monomer in the
densely packed C3Ms. We propose that dimerization of encapsulated EGFP causes a
reorientation of Glu222, resulting in a pKa shift of the chromophore, which is
fully reversible after release of EGFP from the C3Ms at a high ionic strength.
PMID- 28422209
TI - Engineering the strongly correlated properties of bulk Ruddlesden-Popper
transition metal oxides via self-doping.
AB - We demonstrate via first-principles calculations a novel method of tuning the
electron-electron interactions in bulk oxide materials via controlling the
cationic layer arrangement. Using the Ruddlesden-Popper oxides LaSrMnO4 and
LaSrTiO4 as examples, our study demonstrates that a self-doping effect can be
induced by changing the stacking of the neutral and charged cationic layers. It
is believed that such a phenomenon is associated with different movements of
apical oxygen atoms, resulting in diverse bandgaps, magnetism and orbital degrees
of freedom in the same stoichiometric strongly-correlated material. This finding
may open up a new direction to engineer the transition metal oxides for practical
applications requiring tunable electronic properties without external doping.
PMID- 28422212
TI - Trends and challenges for microporous polymers.
AB - Microporous polymers are covalently bound, entirely organic materials which
possess very high surface areas. These materials have been intensively studied
within recent years and various interesting properties and possible applications
have been discovered and described. This review article starts with the question,
what makes microporous polymers special and are there certain features which
differentiate them from other microporous materials? Indeed, there are some
special structural and functional features found in microporous polymers which
make them really unique and merit further exploration. We focus here on
microporous polymers which are solution-processable, can be produced as thin
films on electrodes by oxidative polymerizations, are pi-conjugated organic
semiconductors, or which provide the possibility to introduce and exploit
distinct functional groups in an otherwise non-functional highly porous
environment. Emerging applications for these microporous polymers which make
explicit use of these unique features are further presented.
PMID- 28422213
TI - Revisiting the Julia-Colonna enantioselective epoxidation: supramolecular
catalysis in water.
AB - We describe an efficient epoxidation process leading to chiral epoxyketones using
the reusable homo-oligopeptide poly-l-leucine (PLL) in pure water, without any
organic co-solvent. A range of substituted epoxyketones can be accessed with good
conversions and high enantioselectivities. Based on the experimental results and
computational studies, we propose a mechanism that demonstrates the importance of
both the alpha-helical structure and the presence of a hydrophobic groove of the
homo-oligopeptide catalyst for reactivity and selectivity.
PMID- 28422214
TI - (Diisopropylammonium)2MnBr4: a multifunctional ferroelectric with efficient green
emission and excellent gas sensing properties.
AB - Combination of excellent optical properties and ferroelectricity of hybrid
materials leads to high-performance optoelectronic devices. Here we present a new
organic-inorganic hybrid compound (diisopropylammonium)2MnBr4 (DIPA2MnBr4) which
shows high temperature ferroelectricity accompanied by highly efficient green
light emission. DIPA2MnBr4 also exhibits sensitive and selective optical response
to alcohol vapors.
PMID- 28422216
TI - Design and preparation of efficient hydroisomerization catalysts by the formation
of stable SAPO-11 molecular sieve nanosheets with 10-20 nm thickness and
partially blocked acidic sites.
AB - SAPO-11 nanosheets with partially filled micropores (N-SAPO-11) and a thickness
of 10-20 nm were synthesized using polyhexamethylene biguanide hydrochloride
(PHMB) as a mesoporogen and di-n-propylamine (DPA) as a microporous template.
After Pt loading (0.5 wt%), the Pt/N-SAPO-11 catalyst exhibits higher selectivity
for the isomers and lower selectivity for cracking products than conventional
Pt/SAPO-11 catalysts in the hydroisomerization of n-dodecane.
PMID- 28422217
TI - Increased substrate affinity in the Escherichia coli L28R dihydrofolate reductase
mutant causes trimethoprim resistance.
AB - Dihydrofolate reductase (DHFR) is a ubiquitous enzyme with an essential role in
cell metabolism. DHFR catalyzes the reduction of dihydrofolate to
tetrahydrofolate, which is a precursor for purine and thymidylate synthesis.
Several DHFR targeting antifolate drugs including trimethoprim, a competitive
antibacterial inhibitor, have therefore been developed and are clinically used.
Evolution of resistance against antifolates is a common public health problem
rendering these drugs ineffective. To combat the resistance problem, it is
important to understand resistance-conferring changes in the DHFR structure and
accordingly develop alternative strategies. Here, we structurally and dynamically
characterize Escherichia coli DHFR in its wild type (WT) and trimethoprim
resistant L28R mutant forms in the presence of the substrate and its inhibitor
trimethoprim. We use molecular dynamics simulations to determine the
conformational space, loop dynamics and hydrogen bond distributions at the active
site of DHFR for the WT and the L28R mutant. We also report their experimental
kcat, Km, and Ki values, accompanied by isothermal titration calorimetry
measurements of DHFR that distinguish enthalpic and entropic contributions to
trimethoprim binding. Although mutations that confer resistance to competitive
inhibitors typically make enzymes more promiscuous and decrease affinity to both
the substrate and the inhibitor, strikingly, we find that the L28R mutant has a
unique resistance mechanism. While the binding affinity differences between the
WT and the mutant for the inhibitor and the substrate are small, the newly formed
extra hydrogen bonds with the aminobenzoyl glutamate tail of DHF in the L28R
mutant leads to increased barriers for the dissociation of the substrate and the
product. Therefore, the L28R mutant indirectly gains resistance by enjoying
prolonged binding times in the enzyme-substrate complex. While this also leads to
slower product release and decreases the catalytic rate of the L28R mutant, the
overall effect is the maintenance of a sufficient product formation rate.
Finally, the experimental and computational analyses together reveal the changes
that occur in the energetic landscape of DHFR upon the resistance-conferring L28R
mutation. We show that the negative entropy associated with the binding of
trimethoprim in WT DHFR is due to water organization at the binding interface.
Our study lays the framework to study structural changes in other trimethoprim
resistant DHFR mutants.
PMID- 28422218
TI - The nanostructure of a lithium glyme solvate ionic liquid at electrified
interfaces.
AB - Solvate ionic liquids are a subclass of ionic liquids that have the potential to
be used in a range of electrochemical devices. We present molecular dynamics
simulations of the interfacial structure of thin films of one such lithium based
solvate ionic liquid, [Li(G4)][TFSI], an equimolar solution of tetraglyme and
lithium bistriflimide. This solvate ionic liquid is shown to form a novel
interfacial structure at a plane electrode, which differs in a number of ways
from the nanostructure observed for a conventional ionic liquid at similar
interfaces. This paper explores the structural composition of the interfacial
layers of this solvate ionic liquid, including their variation with surface
charge, and the relation between chemical structure and interfacial arrangement.
PMID- 28422219
TI - A nematic to nematic transformation exhibited by a rod-like liquid crystal.
AB - A novel, highly polar rod-like liquid crystal was found to exhibit two distinct
nematic mesophases (N and NX). When studied by microscopy and X-ray scattering
experiments, and under applied electric fields, the nematic phases are
practically identical. However, calorimetry experiments refute the possibility of
an intervening smectic mesophase, and the transformation between the nematic
phases was associated with a weak thermal event. Analysis of measured dielectric
data, along with molecular properties obtained from DFT calculations, applying
the Maier-Meier relationship allowed for the degree of antiparallel pairing of
dipoles in both nematic phases to be quantified. Based on the results, we
conclude that the onset of the lower temperature phase is driven by the formation
of antiparallel molecular associations.
PMID- 28422221
TI - Designing new catalysts for synthetic fuels: general discussion.
PMID- 28422222
TI - Electron transfer in silicon-bridged adjacent chromophores: the source for blue
green emission.
AB - Si-Bridged chromophores have been proposed as sources for blue-green emission in
several technological applications. The origin of this dual emission is to be
found in an internal charge transfer reaction. The current work is an attempt to
describe the details of these processes in these kinds of substances, and to
design a molecular architecture to improve their performance. Nuclear motions
essential for intramolecular charge transfer (ICT) can involve processes from
twisted internal moieties to dielectric relaxation of the solvent. To address
these issues, we studied ICT between adjacent chromophores in a molecular
compound containing N-isopropylcarbazole (CBL) and 1,4-divinylbenzene (DVB)
linked by a dimethylsilylene bridge. In nonpolar solvents emission arises from
the local excited state (LE) of carbazole whereas in solvents of higher polarity
dual emission was detected (LE + ICT). The CT character of the additional
emission band was concluded from the linear dependence of the fluorescence maxima
on solvent polarity. Electron transfer from CBL to DVB resulted in a large
excited-state dipole moment (37.3 D) as determined from a solvatochromic plot and
DFT calculations. Steady-state and picosecond time-resolved fluorescence
experiments in butyronitrile (293-173 K) showed that the ICT excited state arises
from the LE state of carbazole. These results were analyzed and found to be in
accordance with an adiabatic version of Marcus theory including solvent
relaxation.
PMID- 28422225
TI - Layer-independent and layer-dependent nonlinear optical properties of two
dimensional GaX (X = S, Se, Te) nanosheets.
AB - Recently researchers have found that the non-resonant second-harmonic generation
(SHG) intensity of the GaSe monolayer (ML) is the strongest among all two
dimensional (2D) atomic layered crystals. Here we perform a systematic first
principles study of the SHG coefficient of GaX (X = S, Se, Te) monolayers (MLs)
and few-layers. We find that the non-resonant SHG intensity of the GaS ML can be
comparable with that of the GaSe ML, while the non-resonant SHG intensity of the
GaTe ML is much stronger than that of the GaSe ML. Furthermore, the magnitudes of
SHG coefficients of the few-layers exfoliated from bulk epsilon-GaSe and newly
constructed N1-GaSe crystals are very close to that of the GaSe ML, showing no
dependence on the layer number. The magnitude of the SHG coefficient of the
trilayer exfoliated from the bulk beta-GaSe crystals is around 1/3 of that of the
GaSe ML, decreasing rapidly with the layer number. This study indicates that a
strong SHG response can be obtained in a wide range of monolayers and few-layers.
Moreover, we point out that one can identify the layer number and the stacking
sequence of 2D nanosheets by measuring their elastic constants and SHG
coefficients.
PMID- 28422226
TI - Insights into water-mediated ion clustering in aqueous CaSO4 solutions: pre
nucleation cluster characteristics studied by ab initio calculations and
molecular dynamics simulations.
AB - The molecular structure of growth units building crystals is a fundamental issue
in the crystallization processes from aqueous solutions. In this work, a
systematic investigation of pre-nucleation clusters and their hydration
characteristics in aqueous CaSO4 solutions was performed using ab initio
calculations and molecular dynamics (MD) simulations. The results of ab initio
calculations and MD simulations indicate that the dominant species in aqueous
CaSO4 solutions are monodentate ion-associated structures. Compared with charged
ion clusters, neutral clusters are more likely to be present in an aqueous CaSO4
solution. Neutral (CaSO4)m clusters are probably the growth units involved in the
pre-nucleation or crystallization processes. Meanwhile, hydration behavior around
ion associated species in aqueous CaSO4 solutions plays an important role in
related phase/polymorphism selections. Upon ion clustering, the residence of some
water molecules around Ca2+ in ion-associated species is weakened while that of
some bridging waters is enhanced due to dual interaction by Ca2+ and SO42-. Some
phase/polymorphism selections can be achieved in aqueous CaSO4 solutions by
controlling the hydration around pre-nucleation clusters. Moreover, the
association trend between calcium and sulfate is found to be relatively strong,
which hints at the low solubility of calcium sulfate in water.
PMID- 28422229
TI - Dendritic growth of monolayer ternary WS2(1-x)Se2x flakes for enhanced hydrogen
evolution reaction.
AB - Two-dimensional transition-metal dichalcogenides (TMDs) have attracted much
research interest in the hydrogen evolution reaction (HER) due to their superior
electrocatalytic properties. Beyond binary TMDs, ternary TMD alloys, as
electrocatalysts, were also gradually acknowledged for their remarkable
efficiency in HER. Herein, we successfully synthesized monolayer dendritic
ternary WS2(1-x)Se2x flakes possessing abundant active edge sites on a single
crystalline SrTiO3 (STO(100)). And the obtained dendritic WS2(1-x)Se2x flakes
could be transferred intact to arbitrary substrates, for example, SiO2/Si and Au
foils. Intriguingly, the transferred dendritic WS2(1-x)Se2x flakes on Au foil
demonstrate a significant HER performance, reflected by a rather lower Tafel
slope of ~69 mV dec-1 and a much higher exchange current density of ~50.1 MUA cm
2 outshining other CVD-grown two-dimensional TMD flakes. Furthermore, our new
material shows excellent stability in electro-catalyzing the HER, suggestive of
its robustness for being an excellent electrocatalyst. We believe that this work
broadens the outlook for the synthesis of two-dimensional TMDs toward satisfying
the applications in electrocatalysis.
PMID- 28422232
TI - Editorial of the PCCP themed issue on "Physical Chemistry for Life Sciences".
PMID- 28422233
TI - Detection of stiff nanoparticles within cellular structures by contact resonance
atomic force microscopy subsurface nanomechanical imaging.
AB - Detecting stiff nanoparticles buried in soft biological matrices by atomic force
microscopy (AFM) based techniques represents a new frontier in the field of
scanning probe microscopies, originally developed as surface characterization
methods. Here we report the detection of stiff (magnetic) nanoparticles (NPs)
internalized in cells by using contact resonance AFM (CR-AFM) employed as a
potentially non-destructive subsurface characterization tool. Magnetite (Fe3O4)
NPs were internalized in microglial cells from cerebral cortices of mouse embryos
of 18 days by phagocytosis. Nanomechanical imaging of cells was performed by
detecting the contact resonance frequencies (CRFs) of an AFM cantilever held in
contact with the sample. Agglomerates of NPs internalized in cells were
visualized on the basis of the local increase in the contact stiffness with
respect to the surrounding biological matrix. A second AFM-based technique for
nanomechanical imaging, i.e., HarmoniXTM, as well as magnetic force microscopy
and light microscopy were used to confirm the CR-AFM results. Thus, CR-AFM was
demonstrated as a promising technique for subsurface imaging of nanomaterials in
biological samples.
PMID- 28422235
TI - A facile mechanochemical route to a covalently bonded graphitic carbon nitride (g
C3N4) and fullerene hybrid toward enhanced visible light photocatalytic hydrogen
production.
AB - Graphitic carbon nitride (g-C3N4) as an emerging two-dimensional (2D)
nanomaterial has been commonly used as a metal-free photocatalyst with potential
applications in visible light photocatalytic water-splitting. However, the
photocatalytic activity of g-C3N4 is quite low due to its relatively large band
gap and the existence of contact resistance between the nanosheets. Herein we
report for the first time the facile synthesis of a covalently bonded g-C3N4/C60
hybrid via a solid-state mechanochemical route and its application in
photocatalytic hydrogen production under visible light. The g-C3N4/C60 hybrid was
synthesized by ball-milling g-C3N4 and C60 in the presence of lithium hydroxide
(LiOH) as a catalyst. The hybrid nature and conformation of the g-C3N4/C60 hybrid
were confirmed by a series of spectroscopic and morphological studies, featuring
the covalent bonding of C60 onto the edges of g-C3N4 nanosheets via a four
membered ring of azetidine, which has never been reported in fullerene chemistry.
The g-C3N4/C60 hybrid was further applied to metal-free visible light
photocatalytic hydrogen production, affording a H2 production rate of 266 MUmol h
1 g-1 without using any noble metal cocatalyst such as Pt, which is about 4.0
times higher than that obtained for the pristine g-C3N4 photocatalyst.
PMID- 28422239
TI - Electro-osmosis at surfactant-laden liquid-gas interfaces: beyond standard
models.
AB - Electro-osmosis (EO) is a powerful tool to manipulate liquids in micro and
nanofluidic systems. While EO has been studied extensively at liquid-solid
interfaces, the case of liquid-vapor interfaces, found e.g. in foam films and
bubbles, remains to be explored. Here we perform molecular dynamics (MD)
simulations of EO in a film of aqueous electrolyte covered with fluid layers of
ionic surfactants and surrounded by gas. Following the experimental procedure, we
compute the zeta potential from the EO velocity, defined as the velocity
difference between the middle of the liquid film and the surrounding gas. We show
that the zeta potential can be smaller or larger than existing predictions
depending on the surfactant coverage. We explain the failure of previous
descriptions by the fact that surfactants and bound ions move as rigid bodies and
do not transmit the electric driving force to the liquid locally. Considering the
reciprocal streaming current effect, we then develop an extended model, which can
be used to predict the experimental zeta potential of surfactant-laden liquid-gas
interfaces.
PMID- 28422238
TI - 3D single-molecule tracking enables direct hybridization kinetics measurement in
solution.
AB - Single-molecule measurements of DNA hybridization kinetics are mostly performed
on a surface or inside a trap. Here we demonstrate a time-resolved, 3D single
molecule tracking (3D-SMT) method that allows us to follow a freely diffusing
ssDNA molecule in solution for hundreds of milliseconds or even seconds and
observe multiple annealing and melting events taking place on the same molecule.
This is achieved by combining confocal-feedback 3D-SMT with time-domain
fluorescence lifetime measurement, where fluorescence lifetime serves as the
indicator of hybridization. With sub-diffraction-limit spatial resolution in
molecular tracking and 15 ms temporal resolution in monitoring the change of
reporter's lifetime, we have demonstrated a full characterization of annealing
rate (kon = 5.13 * 106 M-1 s-1), melting rate (koff = 9.55 s-1), and association
constant (Ka = 0.54 MUM-1) of an 8 bp duplex model system diffusing at 4.8 MUm2 s
1. As our method completely eliminates the photobleaching artifacts and diffusion
interference, our kon and koff results well represent the real kinetics in
solution. Our binding kinetics measurement can be carried out in a low signal-to
noise ratio condition (SNR ~ 1.4) where ~130 recorded photons are sufficient for
a lifetime estimation. Using a population-level analysis, we can characterize
hybridization kinetics over a wide range (0.5-125 s-1), even beyond the
reciprocals of the lifetime monitoring temporal resolution and the average track
duration.
PMID- 28422240
TI - Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like
phosphorylase Streptomyces coelicolor GlgEI-V279S.
AB - We synthesized and evaluated new zwitterionic inhibitors against glycoside
hydrolase-like phosphorylase Streptomyces coelicolor (Sco) GlgEI-V279S which
plays a role in alpha-glucan biosynthesis. Sco GlgEI-V279S serves as a model
enzyme for validated anti-tuberculosis (TB) target Mycobacterium tuberculosis
(Mtb) GlgE. Pyrrolidine inhibitors 5 and 6 were designed based on transition
state considerations and incorporate a phosphonate on the pyrrolidine moiety to
expand the interaction network between the inhibitor and the enzyme active site.
Compounds 5 and 6 inhibited Sco GlgEI-V279S with Ki = 45 +/- 4 MUM and 95 +/- 16
MUM, respectively, and crystal structures of Sco GlgE-V279S-5 and Sco GlgE-V279S
6 were obtained at a 3.2 A and 2.5 A resolution, respectively.
PMID- 28422241
TI - Super-tough, ultra-stretchable and strongly compressive hydrogels with core-shell
latex particles inducing efficient aggregation of hydrophobic chains.
AB - Toughness, strechability and compressibility for hydrogels were ordinarily
balanced for their use as mechanically responsive materials. For example,
macromolecular microsphere composite hydrogels with chemical crosslinking
exhibited excellent compression strength and strechability, but poor tensile
stress. Here, a novel strategy for the preparation of a super-tough, ultra
stretchable and strongly compressive hydrogel was proposed by introducing core
shell latex particles (LPs) as crosslinking centers for inducing efficient
aggregation of hydrophobic chains. The core-shell LPs always maintained a
spherical shape due to the presence of a hard core even by an external force and
the soft shell could interact with hydrophobic chains due to hydrophobic
interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited
not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20
times, but also an excellent compressive performance of 13.5 MPa at a strain of
90%. The Mullins effect was verified for the validity of core-shell LP-reinforced
hydrogels by inducing aggregation of hydrophobic chains. The novel strategy
strives to provide a better avenue for designing and developing a new generation
of hydrophobic association tough hydrogels with excellent mechanical properties.
PMID- 28422244
TI - Adhesion and friction in polymer films on solid substrates: conformal sites
analysis and corresponding surface measurements.
AB - In this work, we present a statistical mechanical analysis to elucidate the
molecular-level factors responsible for the static and dynamic properties of
polymer films. This analysis, which we term conformal sites theory, establishes
that three dimensionless parameters play important roles in determining
differences from bulk behavior for thin polymer films near to surfaces: a
microscopic wetting parameter, alphawx, defined as the ratio of polymer-substrate
interaction to polymer-polymer interaction; a dimensionless film thickness, H*;
and dimensionless temperature, T*. The parameter alphawx introduced here provides
a more fundamental measure of wetting than previous metrics, since it is defined
in terms of intermolecular forces and the atomic structure of the substrate, and
so is valid at the nanoscale for gas, liquid or solid films. To test this
theoretical analysis, we also report atomic force microscopy measurements of the
friction coefficient (MU), adhesion force (FA) and glass transition temperature
(Tg) for thin films of two polymers, poly(methyl methacrylate) (PMMA) and
polystyrene (PS), on two planar substrates, graphite and silica. Both the
friction coefficient and the glass transition temperature are found to increase
as the film thickness decreases, and this increase is more pronounced for the
graphite than for the silica surface. The adhesion force is also greater for the
graphite surface. The larger effects encountered for the graphite surface are
attributed to the fact that the microscopic wetting parameter, alphawx, is larger
for graphite than for silica, indicating stronger attraction of polymer chains to
the graphite surface.
PMID- 28422248
TI - Umpolung of protons from H2O: a metal-free chemoselective reduction of carbonyl
compounds via B2pin2/H2O systems.
AB - H2O is routinely described as a proton donor, however, in the presence of diboron
compounds, the umpolung reaction of H2O under metal-free conditions was
successfully developed, which could afford hydride species, leading to a highly
efficient and chemoselective reduction of C[double bond, length as m-dash]O
bonds. This strategy exhibits excellent chemoselectivities toward carbonyl groups
in the presence of ester, olefin, halogen, thioether, sulfonyl, cyano as well as
heteroaromatic groups.
PMID- 28422249
TI - Disulfide bond formation of thiols by using carbon nanotubes.
AB - Clarification of the interactions between carbon nanotubes (CNTs) and
proteinogenic amino acids is a key approach to understanding CNT-protein
interactions. Previous studies have addressed the mechanism of the physical
adsorption of amino acids onto CNTs. However, little is known about their
chemical reactions in aqueous solutions. Here, we established dispersant-free
systems to clarify intrinsic CNT-thiol interactions. We demonstrated that the
redox reaction of CNTs with cysteine, containing a thiol group, leads to
disulfide bond formation between cysteine molecules, even under acidic
conditions. The generality of the redox reaction is validated using other thiols
such as dithiothreitol and glutathione. The present results suggest that
structures of proteins and peptides containing free thiol groups are chemically
modified and misfolded on CNT surfaces by this disulfide bond formation in
biological systems.
PMID- 28422250
TI - A novel nanomissile targeting two biomarkers and accurately bombing CTCs with
doxorubicin.
AB - Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer
survivors to develop deadly metastasis at 3-5 years after surgery; the current
chemotherapies can do nothing about these cells. Herein, we synthesized a novel
doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently
conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the
typical surface biomarkers of colorectal CTCs. The nanomissile can specifically
capture the metastasis-prone CTCs spiked in healthy human blood in a competitive
binding manner. The binding not only accurately delivers DOX into the cancer
cells via the biomarker-mediated endocytosis to inhibit CTC viability through the
DOX-dependent mechanism, but also inhibits the adhesion of cancer cells to the
endothelium and the consequent transmembrane migration through the DOX
independent mechanism. The molecular entity of the conjugate and its
pharmaceutical DOX encapsulation-releasing capacity are well-demonstrated via
various physiochemical characterizations including gel electrophoresis, which
proves the >8-hour biostability of the nanomissile in blood, long enough for it
to chase CTCs in mice and synergistically inhibit the CTC-induced lung metastasis
more potently than its single aptamer-conjugated counterparts and DOX itself. The
present strategy may pave a new avenue for safe and effective cancer metastasis
chemoprevention.
PMID- 28422251
TI - "Anti-Michael addition" of Grignard reagents to sulfonylacetylenes: synthesis of
alkynes.
AB - In this work, the addition of Grignard reagents to arylsulfonylacetylenes, which
undergoes an "anti-Michael addition", resulting in their alkynylation under very
mild conditions is described. The simplicity of the experimental procedure and
the functional group tolerance are the main features of this methodology. This is
an important advantage over the use of organolithium at -78 degrees C that we
previously reported. Moreover, the synthesis of diynes and other examples showing
functional group tolerance in this anti-Michael reaction is also presented.
PMID- 28422253
TI - 3D-printed poly(vinylidene fluoride)/carbon nanotube composites as a tunable, low
cost chemical vapour sensing platform.
AB - We report the production of flexible, highly-conductive poly(vinylidene fluoride)
(PVDF) and multi-walled carbon nanotube (MWCNT) composites as filament feedstock
for 3D printing. This account further describes, for the first time, fused
deposition modelling (FDM) derived 3D-printed objects with chemiresistive
properties in response to volatile organic compounds. The typically prohibitive
thermal expansion and die swell characteristics of PVDF were minimized by the
presence of MWCNTs in the composites enabling straightforward processing and
printing. The nanotubes form a dispersed network as characterized by helium ion
microscopy, contributing to excellent conductivity (~3 * 10-2 S cm-1). The
printed composites contain little residual metal particulate relative to parts
from commercial PLA-nanocomposite material visualized by micro-X-ray computed
tomography (MU-CT) and corroborated with thermogravimetric analysis. Printed
sensing strips, with MWCNT loadings up to 15% mass, function as reversible vapour
sensors with the strongest responses arising with organic compounds capable of
readily intercalating and subsequently swelling the PVDF matrix (acetone and
ethyl acetate). A direct correlation between MWCNT concentration and resistance
change was also observed, with larger responses (up to 161% after 3 minutes)
being generated with decreased MWCNT loadings. These findings highlight the
utility of FDM printing in generating low-cost sensors that respond strongly and
reproducibly to target vapours. Furthermore, the sensors can be easily printed in
different geometries, expanding their utility to wearable form factors. The
proposed formulation strategy may be tailored to sense diverse sets of vapour
classes through structural modification of the polymer backbone and/or
functionalization of the nanotubes within the composite.
PMID- 28422254
TI - A dual enzyme-inorganic hybrid nanoflower incorporated microfluidic paper-based
analytic device (MUPAD) biosensor for sensitive visualized detection of glucose.
AB - A novel microfluidic paper-based analytic device (MUPAD) biosensor is developed
for sensitive and visualized detection of glucose. This biosensor is easily
fabricated using the wax printing technique, with a hybrid nanocomplex composed
of dual enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP) and
Cu3(PO4)2 inorganic nanocrystals incorporated in the detection zones. The hybrid
nanocomplex is found to exhibit a flower-like structure, which allows co
immobilization of these two enzymes in a biocompatible environment. These
nanoflowers not only preserve the activity and enhance the stability of the
enzymes, but also facilitate the transport of the substrates between the two
enzymes. The biosensor is demonstrated to enable rapid and sensitive
quantification of glucose in the concentration range of 0.1-10 mM with a limit of
detection (LOD) of 25 MUM. It is also shown to be applicable to colorimetric
quantitative detection of glucose in human serum and whole blood samples,
implying its potential for clinical applications.
PMID- 28422258
TI - Catalyst-free synthesis of novel dimeric beta-carboline derivatives via an
unexpected [2 + 2 + 2] annulation.
AB - We report here an unexpected catalyst-free [2 + 2 + 2] annulation reaction which
allows access to novel complex dimeric beta-carboline derivatives in a single
step. Various substituted ynones could react with dihydro-beta-carboline imines
to deliver interesting [2 + 2 + 2] annulation products in moderate to good
yields. Alkynoates can also be tolerated in this system.
PMID- 28422260
TI - Measuring the porosity and compressibility of liquid-suspended porous particles
using ultrasound.
AB - A key parameter describing the behavior of suspensions is the volume fraction phi
of the solid particles that are dispersed in the liquid. Obtaining accurate
values for phi becomes difficult for porous particles, because they can absorb
some of the liquid. A prime example are the widely used cornstarch suspensions,
for which phi usually is only estimated from the mass fraction of particles. Here
we present a method to measure the effective porosity and compressibility of
porous particles with ultrasound. We obtain the speed of sound in dilute
cornstarch suspensions at multiple particle concentrations and with different
solvent compressibilities. With the measured particle porosity of 0.31 we are
able to calculate the volume fraction of the saturated particles reliably.
PMID- 28422262
TI - Rifamorpholines A-E, potential antibiotics from locust-associated actinobacteria
Amycolatopsis sp. Hca4.
AB - Cultivation of locust associated rare actinobacteria, Amycolatopsis sp. HCa4, has
provided five unusual macrolactams rifamorpholines A-E. Their structures were
determined by interpretation of spectroscopic and crystallographic data.
Rifamorpholines A-E possess an unprecedented 5/6/6/6 ring chromophore,
representing a new subclass of rifamycin antibiotics. The biosynthetic pathway
for compounds 1-5 involves a key 1,6-cyclization for the formation of the
morpholine ring. Compounds 2 and 4 showed potent activities against methicillin
resistant Staphylococcus aureus (MRSA) with MICs of 4.0 and 8.0 MUM,
respectively.
PMID- 28422263
TI - Synthesis of oxazolidinones: rhodium-catalyzed C-H amination of N
mesyloxycarbamates.
AB - N-Mesyloxycarbamates undergo intramolecular C-H amination reactions to afford
oxazolidinones in good to excellent yields in the presence of rhodium(ii)
carboxylate catalysts. The reaction is performed under green conditions and
potassium carbonate is used, forming biodegradable potassium mesylate as a
reaction by-product. This method enables the production of electron-rich,
electron-deficient, aromatic and heteroaromatic oxazolidinones in good to
excellent yields. Conformationally restricted cyclic secondary N
mesyloxycarbamates furnish cis-oxazolidinones in high yields and selectivity; DFT
calculations are provided to account for the observed selectivity. trans
Oxazolidinones were prepared from acyclic secondary N-mesyloxycarbamates using
Rh2(oct)4. The selectivity was reverted with a cytoxazone N-mesyloxycarbamate
precursor using large chiral rhodium(ii) carboxylate complexes, affording the
corresponding cis-oxazolidinone. This orthogonal selectivity was used to achieve
the formal synthesis of (-)-cytoxazone.
PMID- 28422264
TI - Rhodium-catalyzed addition of sulfonyl hydrazides to allenes: regioselective
synthesis of branched allylic sulfones.
AB - A rhodium-catalyzed regioselective addition of sulfonyl hydrazides to allenes is
reported. With Rh(i)/DPEphos/benzoic acid as the catalyst system, branched
allylic sulfones can be obtained, in good to excellent yields and
regioselectivities.
PMID- 28422265
TI - Nanoporous poly(3-hexylthiophene) thin film structures from self-organization of
a tunable molecular bottlebrush scaffold.
AB - The ability to widely tune the design of macromolecular bottlebrushes provides
access to self-assembled nanostructures formed by microphase segregation in melt,
thin film and solution that depart from structures adopted by simple linear
copolymers. A series of random bottlebrush copolymers containing poly(3
hexylthiophene) (P3HT) and poly(d,l-lactide) (PLA) side chains grafted on a
poly(norbornene) backbone were synthesized via ring-opening metathesis
polymerization (ROMP) using the grafting through approach. P3HT side chains
induce a physical aggregation of the bottlebrush copolymers upon solvent removal
by vacuum drying, primarily driven by attractive pi-pi interactions; however, the
amount of aggregation can be controlled by adjusting side chain composition or by
adding linear P3HT chains to the bottlebrush copolymers. Coarse-grained molecular
dynamics simulations reveal that linear P3HT chains preferentially associate with
P3HT side chains of bottlebrush copolymers, which tends to reduce the
aggregation. The nanoscale morphology of microphase segregated thin films created
by casting P3HT-PLA random bottlebrush copolymers is highly dependent on the
composition of P3HT and PLA side chains, while domain spacing of nanostructures
is mainly determined by the length of the side chains. The selective removal of
PLA side chains under alkaline conditions generates nanoporous P3HT structures
that can be tuned by manipulating molecular design of the bottlebrush scaffold,
which is affected by molecular weight and grafting density of the side chains,
and their sequence. The ability to exploit the unusual architecture of
bottlebrushes to fabricate tunable nanoporous P3HT thin film structures may be a
useful way to design templates for optoelectronic applications or membranes for
separations.
PMID- 28422266
TI - Transient Elastography May Improve Detection of Liver Fibrosis in Psoriasis
Patients Treated with Methotrexate.
PMID- 28422267
TI - Cycling in Canada.
AB - This article provides an overview of cycling, including fatalities and bicycle
helmet use, based on data from the 1994/1995 National Population Health Survey,
the 2013/2014 Canadian Community Health Survey and the Vital Statistics-Death
Database. In 2013/2014, an estimated 7.0 million Canadians aged 12 or older (24%)
reported cycling in the previous three months, compared with 6.5 million (29%) in
1994/95. The prevalence of cycling declined with age, and was more common among
males and people living in higher-income and -education households. From 1994
through 2012, 1,408 cyclists were killed, an average of 74 annually, most of whom
were male (84%). In 2013/2014, 45% of those who had cycled in the past three
months reported that they always wore a helmet.
PMID- 28422268
TI - Housing conditions and respiratory hospitalizations among First Nations people in
Canada.
AB - BACKGROUND: Respiratory diseases are among the leading causes of acute care
hospitalization for First Nations people. Poor housing conditions are associated
with respiratory disorders and may be related to the likelihood of
hospitalization. This analysis examines whether First Nations identity is
associated with higher odds of hospitalization for respiratory conditions
relative to non-Aboriginal persons, and whether such differences in
hospitalization rates remain after consideration of housing conditions. DATA AND
METHODS: Data from the 2006 Census linked to the Discharge Abstract Database were
used to analyze differences in hospitalization for respiratory tract infections
and asthma between First Nations and non-Aboriginal people when housing
conditions were taken into account. RESULTS: Rural on-reserve First Nations
people were more likely than non-Aboriginal people to be hospitalized for a
respiratory tract infection (1.5% versus 0.5%) or for asthma (0.2% versus 0.1%).
For respiratory tract infection hospitalizations, adjustment for housing
conditions, household income and residential location reduced differences, but
the odds remained nearly three times higher for on-reserve First Nations people
(OR = 2.83; CI: 2.69 to 2.99) and two times higher for off-reserve First Nations
people (OR = 2.03; CI: 1.87 to 2.21), compared with the non-Aboriginal cohort.
For asthma hospitalizations, adjustment for household income reduced the odds
more than did adjustment for housing conditions. Even with full adjustment, the
odds of asthma hospitalization relative to non-Aboriginal people remained
significantly higher for First Nations people. INTERPRETATION: First Nations
people are significantly more likely than non-Aboriginal people to be
hospitalized for respiratory tract infections and asthma, even when housing
conditions, household income and residential location are taken into account.
While housing conditions are associated with such hospitalizations, household
income may be more important.
PMID- 28422269
TI - Wake and light therapy for moderate-to-severe depression - a randomized
controlled trial.
AB - OBJECTIVE: To examine the efficacy of using wake and light therapy as a
supplement to standard treatment of hospitalized patients with depression.
METHOD: In this randomized, controlled study, 64 patients with moderate-to-severe
depression were allocated to standard treatment or to the intervention, which
additionally consisted of three wake therapy sessions in one week, 30-min daily
light treatment and sleep time stabilization over the entire nine-week study
period. RESULTS: Patients in the wake therapy group had a significant decrease in
depressive symptoms in week one as measured by HAM-D17 , 17.39 (CI 15.6-19.2) vs.
20.19 (CI 18.3-22.09) (P = 0.04), whereas no statistically significant
differences were found between the groups in weeks two to nine. At week nine, the
wake therapy group had a significantly larger increase in general self-efficacy
(P = 0.001), and waking up during nights was a significantly less frequent
problem (1.9 times vs. 3.2) (P = 0.0008). In most weeks, significantly fewer
patients in the wake therapy group slept during the daytime, and if they slept,
their naps were shorter (week three: 66 min vs. 117 min P = 0.02). CONCLUSION:
The antidepressant effect initially achieved could not be maintained during the
nine-week study period. However, sleep and general self-efficacy improved.
PMID- 28422271
TI - A systematic review of left unilateral electroconvulsive therapy.
AB - OBJECTIVE: To systematically review the published clinical trials, case series,
and case reports on left unilateral (LUL) electrode placement for clinical
electroconvulsive therapy (ECT). METHOD: PubMed, Ovid Medline, and the Cochrane
Library were searched for articles concerning LUL ECT. Number of patients,
efficacy, and cognitive outcomes were extracted from the papers that met our
inclusion criteria. RESULTS: A total of 52 articles were included in this review,
consisting of 33 clinical trials, seven case series, and 12 case reports.
CONCLUSION: Overall, the efficacy of LUL electrode placement for the treatment of
depression and psychosis is similar to that of right unilateral (RUL) and
bilateral (BL) electrode placements. Patients receiving LUL ECT tend to
experience more verbal memory impairment than patients receiving RUL ECT, but
less verbal impairment than patients receiving BL ECT. In contrast, patients
receiving LUL ECT tended to experience the least visual and nonverbal memory
impairment, compared to patients receiving RUL or BL ECT.
PMID- 28422270
TI - Characteristics and Incidence of Chronic Illness in Community-Dwelling
Predominantly Male U.S. Veteran Centenarians.
AB - OBJECTIVES: To assess the incidence of chronic illness and its effect on veteran
centenarians. DESIGN: Retrospective longitudinal cohort study. SETTING: United
States Veterans Affairs Corporate Data Warehouse (CDW). PARTICIPANTS: Community
dwelling veterans born between 1910 and 1915 who survived to at least age 80 (N =
86,892; 31,121 octogenarians, 52,420 nonagenarians, 3,351 centenarians).
MEASUREMENTS: The Kaplan-Meier method was used to estimate cumulative incidence
of chronic conditions according to age group. Incidence rates were compared using
the log-rank test. Cox proportional hazards models were used to estimate
unadjusted hazard ratios. RESULTS: Ninety-seven percent of Centenarians were
male, 88.0% were white, 31.8% were widowed, 87.5% served in World War II, and
63.9% did not have a service-related disability. The incidence rates of chronic
illnesses were higher in octogenarians than centenarians (atrial fibrillation,
15.0% vs 0.6%, P < .001; heart failure, 19.3% vs 0.4%, P < .001; chronic
obstructive pulmonary disease, 17.9% vs 0.6%, P < .001; hypertension, 29.6% vs
3.0%, P < .001; end-stage renal disease, 7.2% vs 0.1%, P < .001; malignancy,
14.1% vs 0.6%, P < .001; diabetes mellitus, 11.1% vs 0.4%, P < .001; stroke, 4.6%
vs 0.4%, P < .001) and in nonagenarians than centenarians (atrial fibrillation,
13.2% vs 3.5%, P < .001; heart failure, 15.8% vs 3.3%, P < .001; chronic
obstructive pulmonary disease, 11.8% vs 3.5%, P < .001; hypertension, 27.2% vs
12.8%, P < .001; end-stage renal disease, 11.9% vs 4.5%, P < .001; malignancy,
8.6% vs 2.3%, P < .001; diabetes mellitus, 7.5% vs 2.2%, P < .001; and stroke,
3.5% vs 1.3%, P < .001). CONCLUSION: In a large cohort of predominantly male
community-dwelling elderly veterans, centenarians had a lower incidence of
chronic illness than those in their 80s and 90s, demonstrating similar
compression of morbidity and extension of health span observed in other studies.
PMID- 28422272
TI - Modeling interactions between a beta-O-4 type lignin model compound and 1-allyl-3
methylimidazolium chloride ionic liquid.
AB - Aiming at understanding the molecular mechanism of the lignin dissolution in
imidazolium-based ionic liquids (ILs), this work presents a combined quantum
chemistry (QC) calculation and molecular dynamics (MD) simulation study on the
interaction of the lignin model compound, veratrylglycerol-beta-guaiacyl ether
(VG) with 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The monomer of VG is
shown to feature a strong intramolecular hydrogen bond, and its dimer is
indicated to present important pi-pi stacking and intermolecular hydrogen bonding
interactions. The interactions of both the cation and anion of [Amim]Cl with VG
are shown to be stronger than that between the two monomers, indicating that
[Amim]Cl is capable of dissolving lignin. While Cl- anion forms a hydrogen-bonded
complex with VG, the imidazolium cation interacts with VG via both the pi-pi
stacking and intermolecular hydrogen bonding. The calculated interaction energies
between VG and the IL or its components (the cation, anion, and ion pair)
indicate the anion plays a more important role than the cation for the
dissolution of lignin in the IL. Theoretical results provide help for
understanding the molecular mechanism of lignin dissolution in imidazolium-based
IL. The theoretical calculations on the interaction between the lignin model
compound and [Amim]Cl ionic liquid indicate that the anion of [Amim]Cl plays a
more important role for lignin dissolution although the cation also makes a
substantial contribution.
PMID- 28422273
TI - A Survey of Women's Awareness of and Reasons for Lack of Postfracture
Osteoporotic Care.
AB - OBJECTIVES: To identify women's beliefs and other factors associated with lack of
osteoporosis (OP) pharmacotherapy (OP-RX) during the 6 months after a fragility
fracture, including the woman's perspective on fracture risk, OP, and treatment.
DESIGN: Cross-sectional. SETTING: Group Health Cooperative, a mixed-model
delivery system. PARTICIPANTS: Female Group Health Cooperative enrollees aged 55
and older with an OP-related fracture according to diagnostic and procedure codes
from January 1, 2013, to March 30, 2014 (N = 985). MEASUREMENTS: OP-RX and
participant characteristics were ascertained from electronic health records
including medications dispensed. A mailed survey was used to obtain data on
health behaviors; OP-related history; concern about, knowledge of, and perceived
risk of future fracture; beliefs about OP-RX; sources of information on OP;
postfracture discussions with providers; and provider recommendations. RESULTS:
The response rate was 73%. Of 634 eligible respondents, 84% did not undergo OP-RX
during the 6 months after fracture. Fewer than 20% of women thought that OP
caused their fracture, 52% did not think they were at risk of future fracture,
and 75% did not think or know whether OP-RX reduces risk of fracture. Knowledge
about OP and the benefits of treatment was higher in the 16% of women who
underwent OP-RX after their fracture. Women reported low levels of engagement
with their healthcare providers regarding OP and fracture risk management.
CONCLUSION: These findings suggest low awareness about OP and its contribution to
fracture risk, lack of understanding about the benefits of pharmacotherapy, and
limited discussion about OP with primary care physicians. Information about
individual's beliefs and knowledge gaps can help design targeted patient and
provider education to improve treatment rates.
PMID- 28422274
TI - Efficacy and tolerance of ruxolitinib in refractory sclerodermatous chronic graft
versus-host disease.
PMID- 28422275
TI - Erratum.
PMID- 28422277
TI - Oxidized LDL, Gamma-Glutamyltransferase and Adverse Outcomes in Older Adults.
AB - OBJECTIVES: Gamma-glutamyltransferase (GGT) is a biomarker of liver disease and
oxidative stress which was associated with all-cause and cardiovascular (CV)
mortality in the general population and in patients with high risk conditions.
This study aims at assessing whether oxLDL modifies the relationship between GGT,
all-cause, and CV mortality in elderly individuals from the general population.
DESIGN: Observational longitudinal study. SETTING: Population-based cohort of
older individuals (>65 years) free of liver disease. PARTICIPANTS: One thousand
and thirty-eight individuals from the Invecchiare in Chianti (InCHIANTI) study.
MEASUREMENTS: Serum GGT level, oxidized low-density lipoprotein (oxLDL), CV
comorbidities, all-cause and CV mortality. RESULTS: The median age of the study
population (n = 1,038) was 74 years (inter-quartile range: 69-79), 152
individuals (15%) had past CV events. During a median follow-up of 9 years, 401
individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT
predicted all-cause mortality (HR for 20 U/L increase in serum GGT: 1.11, 95% CI:
1.02-1.21, P = .02) and CV mortality (HR: 1.17, 95% CI: 1.03-1.33; P = .02).
Furthermore, in an analysis for interaction circulating oxLDL amplified the
effect of GGT on all-cause mortality (P = .003). CONCLUSION: Circulating oxLDL
amplifies the effect of GGT on mortality in the elderly. The mechanism for this
association remains unknown and requires further research, including studying the
potential role of GGT in oxidative stress. These results are consistent with the
hypothesis of a causal role of GGT in the CV morbidity and mortality in older
individuals and indicate that oxLDL plays a crucial role in the interpretation of
the link between GGT and the risk of adverse clinical events in this population.
PMID- 28422278
TI - Decipher test impacts decision making among patients considering adjuvant and
salvage treatment after radical prostatectomy: Interim results from the
Multicenter Prospective PRO-IMPACT study.
AB - BACKGROUND: Patients with prostate cancer and their providers face uncertainty as
they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after
undergoing radical prostatectomy. The authors prospectively evaluated the impact
of the Decipher test, which predicts metastasis risk after radical prostatectomy,
on decision making for ART and SRT. METHODS: A total of 150 patients who were
considering ART and 115 who were considering SRT were enrolled. Providers
submitted a management recommendation before processing the Decipher test and
again at the time of receipt of the test results. Patients completed validated
surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa
related anxiety. RESULTS: Before the Decipher test, observation was recommended
for 89% of patients considering ART and 58% of patients considering SRT. After
Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment
recommendations changed in the ART arm, including 31% among high-risk patients;
and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage
arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS)
scores were better after viewing Decipher test results (ART arm: median DCS
before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before
Decipher, 27 and after Decipher, 23 [P<.001]). PCa-specific anxiety changed after
Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa
specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk
patients. Decipher results reported per 5% increase in 5-year metastasis
probability were associated with the decision to pursue ART (odds ratio, 1.48;
95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable
logistic regression analysis. CONCLUSIONS: Knowledge of Decipher test results was
associated with treatment decision making and improved decisional effectiveness
among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. (c)
2017 American Cancer Society.
PMID- 28422279
TI - Efficacy and Safety of Mechanical Thrombectomy in Older Adults with Acute
Ischemic Stoke.
AB - OBJECTIVES: To evaluate the safety and efficacy of endovascular therapy in
elderly adults treated for acute ischemic stroke. DESIGN: Retrospective cohort
study. SETTING: Comprehensive Stroke Center, University of Tor Vergata, Rome,
Italy. PARTICIPANTS: Elderly adults treated for acute ischemic stroke (N = 219).
MEASUREMENTS: Participants were divided into two groups based on their age (n =
62, >=80; n = 157, <80). Baseline and procedural characteristics, safety outcomes
such as intracranial hemorrhage (ICH) and mortality and efficacy outcomes such as
successful reperfusion and 3-month good clinical outcome of the two groups were
compared. Mutivariable analysis was performed to identify predictors of clinical
outcome. RESULTS: Intravenous thrombolysis was more frequent (67.7% vs 52.8%, P =
.04), and onset to reperfusion time was shorter (318.7 +/- 128.7 vs 282 +/- 53.5,
P = .02) in participants aged 80 and older, but no between-group differences were
found in terms of successful reperfusion (69% vs 63%, P = .4), good clinical
outcome (30.6% vs 34.3%, P = .6), any (37% vs 37.5%, P > .99) or symptomatic (11%
vs 14%, P = .6) ICH, or mortality (40.3% vs 29.2%, P = .14). Multivariable
analysis revealed that, in the older group, onset National Institute of Health
Stroke Scale (NIHSS) score (odds ratio (OR) = 0.65, 95% confidence interval (CI)
= 0.44-0.96, P = .03) and 24-hour clinical improvement (OR = 141.13, 95% CI =
2.96-6,720.7, P = .01) were independent predictors of 3-month functional
independence. CONCLUSION: These findings suggest that endovascular treatment for
stroke in selected elderly adults could be safe and effective. Major determinants
of outcome in this subgroup of elderly patients are presentation NIHSS score and
24-hour clinical improvement.
PMID- 28422281
TI - WNK1/HSN2 founder mutation in patients with hereditary sensory and autonomic
neuropathy: A Japanese cohort study.
AB - The clinical and genetic spectrum of hereditary sensory and autonomic neuropathy
(HSAN) is still unknown in Japan. We collected a broad cohort of 33 unrelated
patients with predominant sensory and/or autonomic dysfunctions, who were
referred to our genetic laboratory. A gene panel sequencing targeting 18 HSAN
related genes was performed using a next-generation sequencing system. A
recurrent frame shift mutation in the WNK1/HSN2 gene, c.3237_3238insT
(p.Asp1080*), was detected in 5 patients. This mutation was homozygous in 4 cases
and of a compound heterozygous genotype in 1 case. Geographic and haplotype
analysis of all 5 patients suggested a founder event. In addition, a novel
heterozygous nonsense variant, c.2615C>G (p.Ser872*), was identified. All the 5
patients presented with severe sensory and autonomic dysfunctions at birth or
during adolescence. In 2 patients, an uncommon phenotype of acute pathological
pain presented at ~50 years of age. Here, we present the first founder mutation
of WNK1/HSN2, in addition to French Canadian, which accounts for ~15.2% of
Japanese patients with HSAN in our cohort. We have also reviewed all previously
described mutations in WNK1/HSN2 and reconciled their nomenclature strategy on
the basis of the current longest transcript.
PMID- 28422280
TI - Integrating Frailty Research into the Medical Specialties-Report from a U13
Conference.
AB - Although the field of frailty research has expanded rapidly, it is still a
nascent concept within the clinical specialties. Frailty, conceptualized as
greater vulnerability to stressors because of significant depletion of
physiological reserves, predicts poorer outcomes in several medical specialties,
including cardiology, human immunodeficiency virus care, and nephrology, and in
the behavioral and social sciences. Lack of a consensus definition, proliferation
of measurement tools, inadequate understanding of the biology of frailty, and
lack of validated clinical algorithms for frail individuals hinders incorporation
of frailty assessment and frailty research into the specialties. In 2015, the
American Geriatrics Society, the National Institute on Aging (NIA), and the
Alliance for Academic Internal Medicine held a conference for awardees of the NIA
sponsored Grants for Early Medical/Surgical Specialists Transition into Aging
Research program to review the current state of knowledge regarding frailty in
the subspecialties and to highlight examples of integrating frailty research into
the medical specialties. Research questions to advance frailty research into
specialty medicine are proposed.
PMID- 28422282
TI - Analysis of Circulating miR-1, miR-23a, and miR-26a in Atrial Fibrillation
Patients Undergoing Coronary Bypass Artery Grafting Surgery.
AB - Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery.
From a pathophysiological point of view, a myriad of factors such as trauma,
atrial dilation, ischemia, mechanical myopericarditis, autonomic imbalance, loss
of connexins, AF nest remodeling, inflammation, sutures, and dysfunction caused
by postextracorporeal circulation can contribute to postoperative atrial
fibrillation (POAF) resulting in a longer hospital stay and consequently higher
cost. Recent studies showed that short fragments of RNA, called microRNA (miRNA),
can contribute to the development of several cardiovascular diseases, including
AF. The aim of this study was to evaluate the levels of circulating miRNAs (miR
1, -23a, and -26a) that can be involved in POAF. Patients submitted to coronary
artery bypass graft surgery were grouped in POAF (24 patients) and without POAF
(24 patients). Results showed older age, longer clamp-time, and more days in the
intensive care unit as well as a longer total hospital stay in the POAF group.
Preoperative levels of circulating miRNAs were similar. Analysis of miRNAs
revealed significantly lower circulating levels of miRNA-23a (P = 0.02) and
26a (P = 0.01) in the POAF group during the postoperative period. Receiver
operating characteristic (ROC) analysis showed the area under the ROC curve of
miR-23a and miR-26a for predicting FA was 0.63 (95% confidence interval [CI]:
0.51-0.74; P = 0.02) and 0.66 (95% CI: 0.55-0.77; P = 0.01), respectively.
Our data suggests that circulating miRNA-23a and -26a may be involved in the
underlying biology of postoperative AF development.
PMID- 28422283
TI - Agarose hydrogel induced MCF-7 and BMG-1 cell line progressive 3D and 3D revert
cultures.
AB - 3D culture systems have enhanced the utility of cancer cell lines as they are
considered closer to the in vivo systems. A variety of changes are induced in
cells cultured in 3D systems; an apparent and striking feature being the
spontaneous acquisition of distinct morphological entities. 3D reverts (3DRs) can
be obtained by introducing 3D aggregates in scaffold/matrix-free culture units.
It could be seen that the two cell lines used in this study exhibited differences
in 3DR structures, though both were cultured on agarose hydrogels. Also,
differences in 3DR formation, growth and survival were different. While 3D
aggregates of several cell lines have been reported for a variety of studies,
there are no studies that describe or utilize 3DRs. 3DRs can provide insights
into complex events that can occur in cancer cells; especially as material to
study metastasis, migration, and invasion.
PMID- 28422284
TI - Is a larger refuge always better? Dispersal and dose in pesticide resistance
evolution.
AB - The evolution of resistance against pesticides is an important problem of modern
agriculture. The high-dose/refuge strategy, which divides the landscape into
treated and nontreated (refuge) patches, has proven effective at delaying
resistance evolution. However, theoretical understanding is still incomplete,
especially for combinations of limited dispersal and partially recessive
resistance. We reformulate a two-patch model based on the Comins model and derive
a simple quadratic approximation to analyze the effects of limited dispersal,
refuge size, and dominance for high efficacy treatments on the rate of evolution.
When a small but substantial number of heterozygotes can survive in the treated
patch, a larger refuge always reduces the rate of resistance evolution. However,
when dominance is small enough, the evolutionary dynamics in the refuge
population, which is indirectly driven by migrants from the treated patch, mainly
describes the resistance evolution in the landscape. In this case, for small
refuges, increasing the refuge size will increase the rate of resistance
evolution. Our analysis distils major driving forces from the model, and can
provide a framework for understanding directional selection in source-sink
environments.
PMID- 28422285
TI - Hematopoietic stem/progenitor cell differentiation towards myeloid lineage is
modulated by LIGHT/LIGHT receptor signaling.
AB - The cytokine LT-related inducible ligand that competes for glycoprotein D binding
to herpesvirus entry mediator on T cells (LIGHT) is a member of the tumor
necrosis factor (TNF) superfamily. It is expressed primarily on activated T
lymphocytes, and detectable on monocytes, granulocytes, and immune dendritic
cells. It mainly plays a role in immune regulation including T cell activation
and dendritic cell maturation. We recently reported its role as an inducer in
embryonic stem cell differentiation, but its role in regulation of adult stem
cell has not been defined. In the present study, we examined the expression of
LIGHT receptor in Lin- c-kit+ Sca-1+ hematopoietic stem/progenitor cells
(HSC/HPCs). We found that HSC express HVEM, a LIGHT receptor, on its surface. We
further identified the role of LIGHT in promoting myeloid differentiation of HSCs
driven by granulocyte-monocyte colony stimulating factor (GM-CSF). Further
studies showed that LIGHT enhances both GM-CSF and GM-CSF receptor (GM-CSFR)
expression in HSCs. LIGHT stimulation increases PU.1 expression in HSC/HPCs. In
vivo administration of LIGHT increases the colony-forming unit
granulocyte/monocyte (CFU-GM) colony formation and plasma GM-CSF level.
Altogether, the data suggest LIGHT promote myeloid differentiation of HSC/HPCs.
PMID- 28422286
TI - Isorhapontigenin induced cell growth inhibition and apoptosis by targeting EGFR
related pathways in prostate cancer.
AB - Isorhapontigenin (ISO), a naturally phytopolyphenol compound existing in Chinese
herb, apples, and various vegetables, has attracted extensive interest in recent
years for its diverse pharmacological characteristics. Increasing evidences
reveal that ISO can inhibit cancer cell growth by induced apoptosis, however, the
molecular mechanisms is not fully understood. In this study, we found for the
first time that ISO apparently induced cell growth inhibition and apoptosis by
targeting EGFR and its downstream signal pathways in prostate cancer (PCa) cells
both in vitro and in vivo, whereas no obviously effect on normal prostate cells.
From the results, we found that ISO competitively targeted EGFR with EGF and
inhibited EGFR auto-phosphorylation, and then decreased the levels of p-Erk1/2, p
PI3 K, and p-AKT, and further induced down-regulation of p-FOXO1 and promoted
FOXO1 nuclear translocation; and finally resulted in a significantly up
regulation of Bim/p21/27/Bax/cleaved Caspase-3/cleaved PARP-1 and a markedly down
regulation of Sp1/Bcl-2/XIAP/Cyclin D1. Moreover, our experimental data
demonstrated that treatment of ISO decreased protein level of AR via both
inhibiting the expression of AR gene and promoting the ubiquitination/degradation
of AR proteins in proteasome. In vivo, we also found that ISO inhibited the
growth of subcutaneous xenotransplanted tumor in nude mice by inducing PCa cell
growth inhibition and apoptosis. Taken together, all findings here clearly
implicated that EGFR-related signal pathways, including EGFR-PI3K-Akt and EGFR
Erk1/2 pathways, were involved in ISO-induced cell growth inhibition and
apoptosis in PCa cells, providing a more solid theoretical basis for the
application of ISO to treat patients with prostate cancer in clinic.
PMID- 28422288
TI - General dentists' awareness of how to cope with medical emergencies in paediatric
dental patients.
AB - BACKGROUND: General dentists (GDs) should be aware of the symptoms, signs,
diagnoses and treatment of medical emergencies in paediatric patients. AIM: To
evaluate the knowledge of GDs in coping with medical emergencies, and to identify
whether they are confident to diagnose and treat medical emergencies in
paediatric patients. DESIGN: The questionnaire was conducted immediately before
the beginning of national dental meetings and continuing education seminars in
Croatia, attended by the GDs, in order to obtain a representative sample.
RESULTS: Of a total of 498 GDs who returned the questionnaire with valid data,
51.2% reported that a medical history was regularly taken. A high proportion
(81.3%) of the GDs had never received any basic life support (BLS) training and
education for paediatric patients during their undergraduate studies. After
graduation, this value rose to 86.1% of GDs. However, more than two-thirds
(68.7%) had experienced some emergency situation in their practice. The most
frequent emergency was vasovagal syncope (83.6%) and the most rare was cardiac
arrest (8.2%). One-fifth (20.5%) of GDs experienced some emergency but could not
make a diagnosis. The more BLS training undergone by a GD, the more self
confident s/he felt in an emergency situation. CONCLUSIONS: Most GDs have a lack
of knowledge to cope with medical emergencies in paediatric patients, and do not
feel confident to diagnose and treat emergency situations in children. It is
suggested that adequate training and education should be provided for all GDs to
address this shortcoming.
PMID- 28422287
TI - Genetic variants as potential predictive biomarkers in advanced colorectal cancer
patients treated with oxaliplatin-based chemotherapy.
AB - Chemotherapy regimen containing oxaliplatin is often the first-line treatment for
patient with advanced colorectal cancer. Oxaliplatin binds to DNA, leading to the
formation of crosslinks and bulky adducts. Approximately 50% of patients with CRC
benefit from treatment with oxaliplatin. It is possible that genetic variants in
biological pathways involved in drug transportation, drug metabolism, DNA damage
repair, and cell cycle modulation might affect the activity, or efficacy of
oxaliplatin. Because oxaliplatin resistance may be related to these genetic
variants and may therefore be an important reason for treatment failure, we have
summarized the genetic variations that have been reported to be predictive
markers of the response to oxaliplatin based therapy in patients with advanced
CRC.
PMID- 28422289
TI - Dietary Tuna Dark Muscle Protein Attenuates Hepatic Steatosis and Increases Serum
High-Density Lipoprotein Cholesterol in Obese Type-2 Diabetic/Obese KK-Ay Mice.
AB - Tuna muscle consists of light and dark muscle in approximately equal proportions.
However, besides for the light muscle of tuna, cod, sardine, and salmon, few
researches have assessed the health-promoting functions of fish protein.
Therefore, we evaluated the mechanisms underlying the alteration of lipid storage
and cholesterol metabolism following the intake of tuna dark muscle protein
(TDMP) by obese type-2 diabetic/obese mice. Four-week-old male KK-Ay mice were
separated into 2 dietary groups, with one group receiving a casein-based diet and
the other receiving a diet with the substitution of part of the protein (50%,
w/w) by TDMP (TDMP diet) for 4 wk. The TDMP diet significantly increased the
content of serum high-density lipoprotein cholesterol, partly due to the
reduction of the expression of scavenger receptor class B member 1 in epididymal
white adipose tissue. In addition, dietary TDMP decreased the content of hepatic
triacylglycerol, which could be due to the enhancement of carnitine
palmitoyltransferase-2 activity through the activation of the expression of the
peroxisome proliferative activated receptor-alpha in the liver. These results
suggest that TDMP could have the potential to prevent the development of obesity
related diseases by suppressing the storage of hepatic triacylglycerol and
cholesterol.
PMID- 28422290
TI - Heroin-related Deaths from the Hennepin County Medical Examiner's Office from
2004 Through 2015.
AB - Over the past two decades, prescription and illicit opioid use has led to changes
in public health policy to address the increasing number of opioid-related
deaths. The purpose of this study was to review cases from Hennepin County
Medical Examiner's Office between 2004 through 2015 where heroin was listed as a
significant contributor or as the cause of death. We identified 322 heroin
related deaths, which were predominantly male (255; 79%). 6-Monoacetylmorphine (6
MAM) median (range) concentrations were as follows: blood (n = 7), 0.010 (0.006
0.078) mg/L; urine (n = 30), 0.359 (0.009-1.75) mg/L; and vitreous humor (n =
31), 0.034 (0.004-0.24) mg/L. Free morphine was measurable in 273 cases and the
percent free morphine (range), when grouped by COD, was opioid (n = 124), 28%
(2.2%-92%), and mixed drug toxicity (n = 135), 35.3% (1.5%-100%); (p < 0.01).
Quantitation of 6-MAM in blood and vitreous humor, along with a free to total
morphine ratio >26%, was useful in establishing heroin-related deaths.
PMID- 28422291
TI - Barriers and Facilitators to Integrating Health Service Responses to Intimate
Partner Violence in Low- and Middle-Income Countries: A Comparative Health
Systems and Service Analysis.
AB - This systematic review synthesizes 11 studies of health-sector responses to
intimate partner violence (IPV) in low- and middle-income countries. The services
that were most comprehensive and integrated in their responsiveness to IPV were
primarily in primary health and antenatal care settings. Findings suggest that
the following facilitators are important: availability of clear guidelines,
policies, or protocols; management support; intersectoral coordination with
clear, accessible on-site and off-site referral options; adequate and trained
staff with accepting and empathetic attitudes toward survivors of IPV; initial
and ongoing training for health workers; and a supportive and supervised
environment in which to enact new IPV protocols. A key characteristic of the most
integrated responses was the connection or "linkages" between different
individual factors. Irrespective of their service entry point, what emerged as
crucial was a connected systems-level response, with all elements implemented in
a coordinated manner.
PMID- 28422292
TI - High-theabrownins instant dark tea product by Aspergillus niger via submerged
fermentation: alpha-glucosidase and pancreatic lipase inhibition and antioxidant
activity.
AB - BACKGROUND: Theabrownins (TB) are bioactive components that are usually extracted
from Chinese dark tea, in which they are present at low concentrations. The
present study aimed to produce an instant dark tea high in theabrownins via
submerged fermentation by the fungus Aspergillus niger. Three fermentation
parameters that affect theabrownins content (i.e. inoculum size, liquid-solid
ratio and rotation speed) were optimized using response surface methodology.
RESULT: Optimum fermentation conditions were modeled to be an inoculum of 5.40%
(v/v), a liquid-solid ratio of 27.45 mL g-1 and a rotation speed of 184 rpm and
were predicted to yield 292.99 g kg-1 TB. Under these experimentally conditions,
the TB content of the instant dark tea was 291.93 g kg-1 . The antioxidant
capacity and alpha-glucosidase and pancreatic lipase inhibitory activities of the
high-TB instant black tea were higher than four other typical instant dark tea
products. CONCLUSION: The results of the present study show that careful
management of culture conditions can produce a dark tea high in theabrownins.
Furthermore, high-theabrownins instant dark tea could serve as a source of
bioactive products and be used in functional foods as an ingredient imparting
antioxidant properties and the ability to inhibit pancreatic lipase and alpha
glucosidase. (c) 2017 Society of Chemical Industry.
PMID- 28422293
TI - An autocrine ATP release mechanism regulates basal ciliary activity in airway
epithelium.
AB - KEY POINTS: Extracellular ATP, in association with [Ca2+ ]i regulation, is
required to maintain basal ciliary beat frequency. Increasing extracellular ATP
levels increases ciliary beating in airway epithelial cells, maintaining a
sustained response by inducing the release of additional ATP. Extracellular ATP
levels in the millimolar range, previously associated with pathophysiological
conditions of the airway epithelium, produce a transient arrest of ciliary
activity. The regulation of ciliary beat frequency is dependent on ATP release by
hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of
which may even stop ciliary movement. The force exerted by cilia, measured by
atomic force microscopy, is reduced following extracellular ATP hydrolysis. This
result complements the current understanding of the ciliary beating regulatory
mechanism, with special relevance to inflammatory diseases of the airway
epithelium that affect mucociliary clearance. ABSTRACT: Extracellular
nucleotides, including ATP, are locally released by the airway epithelium and
stimulate ciliary activity in a [Ca2+ ]i -dependent manner after mechanical
stimulation of ciliated cells. However, it is unclear whether the ATP released is
involved in regulating basal ciliary activity and mediating changes in ciliary
activity in response to chemical stimulation. In the present study, we evaluated
ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from
mouse tracheal epithelium, using videomicroscopy and atomic force microscopy
(AFM), respectively. Extracellular ATP levels and [Ca2+ ]i were measured by
luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide
was measured to evaluate hemichannel functionality. We show that hydrolysis of
constitutive extracellular ATP levels with apyrase (50 U ml-1 ) reduced basal CBF
by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by
carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an antagonist used to
block P2X7 receptors, which reduced basal CBF by 85%. Additionally, increasing
extracellular ATP levels (0.1-100 MUm) increased CBF, maintaining a sustained
response that was suppressed in the presence of carbenoxolone. We also show that
high levels of ATP (1 mm), associated with inflammatory conditions, lowered basal
CBF by reducing [Ca2+ ]i and hemichannel functionality. In summary, we provide
evidence indicating that airway epithelium ATP release is the molecular autocrine
mechanism regulating basal ciliary activity and is also the mediator of the
ciliary response to chemical stimulation.
PMID- 28422294
TI - Antiviral activity of exopolysaccharides from Arthrospira platensis against koi
herpesvirus.
AB - Although koi herpesvirus (KHV) has a history of causing severe economic losses in
common carp and koi farms, there are still no treatments available on the market.
Thus, the aim of this study was to test exopolysaccharides (EPS) for its
antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in
common carp brain cells. These substances can be easily extracted from
extracellular algae supernatant and were identified as groups of sulphated
polysaccharides. In order to reach this aim, Arthrospira platensis, which is well
known for its antiviral activity of intra- and extracellular compounds towards
mammalian herpesviruses, was investigated as standard organism and compared to
commercial antiviral drug, ganciclovir, which inhibits the viral DNA
polymerization. The antiviral activity of polysaccharides of A. platensis against
KHV was confirmed in vitro using qualitative assessment of KHV life cycle genes,
and it was found by RT-PCR that EPS, applied at a concentration of >18 MUg mL-1
and a multiplicity of infection (MOI) of 0.45 of KHV, suppressed the viral
replication in common carp brain (CCB) cells even after 22 days post-infection,
entirely. Further, this study presents first data indicating an enormous
potential using polysaccharides as an additive for aquacultures to lower or
hinder the spread of the KHV and koi herpesvirus disease (KHVD) in future.
PMID- 28422295
TI - In vivo and in vitro studies using larval and adult antigens from Neobenedenia
melleni on immune response in yellowtail (Seriola lalandi).
AB - Neobenedenia melleni is a monogenean parasite that causes significant mortality
and economic losses in fish aquaculture. Changes in the antigenic composition of
this parasite occur during its developmental stages. In this study, we evaluated
humoral parameters in serum and transcriptional immune responses of yellowtail
naturally infected with N. melleni. In addition, in vitro assays were performed
to study the stimulatory effects of antigens from larvae and adults on spleen
leucocytes from non-infected fish at 6 and 24 h post-stimulation. The results
showed enhanced total protein, myeloperoxidase and antiprotease activities in N.
melleni-infected fish compared with non-infected ones. The induction of Toll-like
receptors (TLRs) and pro-inflammatory cytokines in spleen leucocytes during
natural infection with N. melleni suggests that these immune-related genes play
an important role in the initiation of the immune defence mechanism for
controlling parasite infection. Interestingly, the magnitude of in vitro
responses of spleen leucocytes was dependent on the parasitic stage. An important
stimulation of gene expression by adult antigens on spleen leucocytes was
observed. Differential expression patterns of TLRs and target cytokines in
yellowtail leucocytes in both in vivo and in vitro studies suggest that the
quality of yellowtail immune response is conditioned by N. melleni development.
PMID- 28422296
TI - Keeping out and getting in: reframing emergency department gatekeeping as
structural competence.
AB - Sociologists have tended to frame medical gatekeeping as an exclusionary social
practice, delineating how practitioners and clerical staff police the moral
boundaries of medicine by keeping out patients who are categorised as 'bad',
'deviant', or otherwise problematic. Yet medical gatekeeping, understood more
broadly, can include not only keeping patients out of particular clinical
settings, but also redirecting them to alternative sources of care. In this
article, I draw on qualitative analysis of audio-recorded patient-provider
interactions in a United States emergency department (ED) to illustrate medical
gatekeeping as a two-step process of, first, categorising certain patient
complaints as unsuitable for treatment within a particular setting, and second,
diverting patients to alternative sites for care. I refer to these as the
restrictive and facilitative components of medical gatekeeping to denote how each
relates to patients' access to care, recognising that both components of medical
gatekeeping are part of a coordinated organisational strategy for managing
resource scarcity. By illustrating how ED providers reveal intimate knowledge of
structural vulnerabilities in diverting socioeconomically disadvantaged patients
with chronic back pain to clinical sites that are better equipped to provide
care, I suggest that we rethink the emphasis on restrictive practices in
sociological accounts of medical gatekeeping.
PMID- 28422297
TI - Piecing together the aggression puzzle: Testing the mediating variables linking
early to later aggression.
AB - Results from several studies show that early aggression predicts later
aggression; however, few studies have examined the mediating mechanisms in these
relations. The paucity of research that has tested mediation found that
aggressive motives and hostile attributions are important causal processes. This
past work is limited by not measuring aggression multiple times throughout the
study to test aggression change over time and the variables that mediate such
change. The current study had participants (N = 90) interact with a same-sex
confederate on a modified version of the Tangram Task-our measure of aggressive
behavior-for three trials. At each trial, participants completed a measure of
aggressive motivations, assigned tangram puzzles for their partner to solve, were
provoked (or not) by their ostensible partner, and then completed an assessment
of aggressive attributions regarding their partner's behavior. Results showed
that, for provoked participants, the relation between Time 1 aggressive
attributions predicted Time 3 aggressive behavior through the following temporal
mediated pathway: Time 2 aggressive attributions, Time 2 aggressive behavior, and
Time 3 aggressive motivations.
PMID- 28422298
TI - Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in
the Quest for the Molecules With Therapeutic and Preventive Potential.
AB - Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age-related amyloid
diseases that affect millions of people worldwide. Broadly supported by
epidemiological data, the higher incidence of AD among type 2 diabetic patients
led to the recognition of T2D as a tangible risk factor for the development of
AD. Indeed, there is now growing evidence on brain structural and functional
abnormalities arising from brain insulin resistance and deficiency, ultimately
highlighting the need for new approaches capable of preventing the development of
AD in type 2 diabetic patients. This review provides an update on overlapping
pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic
events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity,
and even shared genetic background. These events will be presented as puzzle
pieces put together, thus establishing potential therapeutic targets for drug
discovery and development against T2D and diabetes-induced cognitive decline-a
heavyweight contributor to the increasing incidence of dementia in developed
countries. Hoping to pave the way in this direction, we will present some of the
most promising and well-studied drug leads with potential against both
pathologies, including their respective bioactivity reports, mechanisms of
action, and structure-activity relationships.
PMID- 28422299
TI - Incorporation of pre-therapy 18 F-FDG uptake data with CT texture features into a
radiomics model for radiation pneumonitis diagnosis.
AB - PURPOSE: To determine whether the addition of standardized uptake value (SUV)
from PET scans to CT lung texture features could improve a radiomics-based model
of radiation pneumonitis (RP) diagnosis in patients undergoing radiotherapy.
METHODS AND MATERIALS: Anonymized data from 96 esophageal cancer patients (18 RP
positive cases of Grade >= 2) were collected including pre-therapy PET/CT scans,
pre-/post-therapy diagnostic CT scans and RP status. Twenty texture features
(first-order, fractal, Laws' filter and gray-level co-occurrence matrix) were
calculated from diagnostic CT scans and compared in anatomically matched regions
of the lung. Classifier performance (texture, SUV, or combination) was assessed
by calculating the area under the receiver operating characteristic curve (AUC).
For each texture feature, logistic regression classifiers consisting of the
average change in texture feature value and the pre-therapy SUV standard
deviation (SUVSD ) were created and compared with the texture feature as a lone
classifier using ANOVA with correction for multiple comparisons (P < 0.0025).
RESULTS: While clinical parameters (mean lung dose, smoking history, tumor
location) were not significantly different among patients with and without
symptomatic RP, SUV and texture parameters were significantly associated with RP
status. AUC for single-texture feature classifiers alone ranged from 0.58 to 0.81
and 0.53 to 0.71 in high-dose (>= 30 Gy) and low-dose (< 10 Gy) regions of the
lungs, respectively. AUC for SUVSD alone was 0.69 (95% confidence interval: 0.54
0.83). Adding SUVSD into a logistic regression model significantly improved model
fit for 18, 14 and 11 texture features and increased the mean AUC across features
by 0.08, 0.06, and 0.04 in the low-, medium-, and high-dose regions,
respectively. CONCLUSIONS: Addition of SUVSD to a single-texture feature improves
classifier performance on average, but the improvement is smaller in magnitude
when SUVSD is added to an already effective classifier using texture alone. These
findings demonstrate the potential for more accurate assessment of RP using
information from multiple imaging modalities.
PMID- 28422301
TI - Meeting the Reproductive Health Needs of Female Key Populations Affected by HIV
in Low- and Middle-Income Countries: A Review of the Evidence.
AB - Female sex workers and other women at high risk of acquiring HIV have the right
to sexual and reproductive health, including the right to determine the number
and timing of pregnancies. We conducted a literature review to examine the data
that exist regarding the family planning and reproductive health needs of female
key populations, the underlying determinants of these populations' vulnerability
to poor reproductive health outcomes, and the obstacles they face in accessing
high-quality reproductive health services. Findings indicate that female key
populations experience high rates of unmet need for family planning and safer
conception services, unintended pregnancies, sexual violence, and abortion, and
that they practice inconsistent condom use. Restrictive policy environments,
stigma and discrimination in health care settings, gender inequality, and
economic marginalization restrict access to services and undermine the ability to
safely achieve reproductive intentions. We offer recommendations for structural,
health system, community, and individual-level interventions that can mitigate
the effects of these barriers and improve reproductive health outcomes.
PMID- 28422300
TI - Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin
in patients with stable coronary disease before percutaneous coronary
intervention: The STATIPLAT randomized study.
AB - BACKGROUND: The acute effects of statin loading dose (LD) on platelet reactivity
in patients with chronic stable angina (CSA) are not completely clear.
HYPOTHESIS: We hypothesized that LDs of atorvastatin and rosuvastatin have
different pharmacodynamic acute effects on platelet aggregability in CSA patients
with baseline normal platelet reactivity while on dual antiplatelet therapy
(DAPT). METHODS: From September 2011 to February 2014, all consecutive CSA
patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective
percutaneous coronary intervention (PCI). An initial assessment of platelet
reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively,
indicative of the response to clopidogrel and aspirin) was performed with
impedance aggregometry. Patients with high platelet reactivity to ADP test (area
under the curve >47) were excluded. The remaining patients were randomized into 3
treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg;
and Group C, no statin LD (control group). A second assessment of platelet
reactivity was performed >=12 hours after statin LD. RESULTS: 682 patients were
screened and 145 were randomized into the 3 groups. At baseline and after statin
LD, no significant difference was found in platelet reactivity in response to 3
different agonists between the 3 groups. Subgroup analysis showed that platelet
reactivity to ADP test was significantly lower in patients chronically treated
with low-dose statins (n = 94) compared with statin-naive patients (n = 51; 15.32
+/- 1.50 vs 18.59 +/- 1.30; P = 0.007). CONCLUSIONS: Loading dose of atorvastatin
(80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet
reactivity in CSA patients with baseline reduced platelet reactivity as in
chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose
statins and clopidogrel resulted in significantly lower platelet reactivity
compared with clopidogrel alone.
PMID- 28422302
TI - Recombinant PirA-like toxin protects shrimp against challenge with Vibrio
parahaemolyticus, the aetiological agent of acute hepatopancreatic necrosis
disease.
PMID- 28422303
TI - Smoking increased the risk of prostate cancer with grade group >= 4 and
intraductal carcinoma in a prospective biopsy cohort.
AB - OBJECTIVE: To investigate the association between smoking and different prostate
cancer (PCa) pathological subtypes incidence in Chinese men. PATIENTS AND
METHODS: We prospectively included 1795 patients who underwent prostate biopsies
in one tertiary center between March 2013 and April 2016. Clinical data and
biopsy outcomes were collected. Logistic regression was used to evaluate the
association between cigarette smoking and PCa incidence. RESULTS: A total of 737
men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade
group >= 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the
prostate (IDC-P), respectively. Current smokers had a significantly higher risk
of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association
was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61
1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher
risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50,
95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never
smokers (OR = 2.29, 95%CI: 1.14-4.59). CONCLUSION: Among men in this Chinese
biopsy cohort, current smoking was associated with highly malignant PCa
incidence, such as HGPCa and IDC-P. The duration of smoking may be associated
with HGPCa.
PMID- 28422304
TI - Antibiotic treatment of zebrafish mycobacteriosis: tolerance and efficacy of
treatments with tigecycline and clarithromycin.
AB - Zebrafish (Danio rerio) are a popular model organism used in a growing number of
research fields. Maintaining healthy, disease-free laboratory fish is important
for the integrity of many of these studies. Mycobacteriosis is a chronic
bacterial infection caused by several Mycobacterium spp. and is the second most
common disease found in laboratory zebrafish. Current mycobacteriosis control
measures recommend the removal of infected fish and in severe outbreaks,
depopulation. These measures can be effective, but less disruptive measures
should be assessed for controlling mycobacteriosis, particularly when valuable
and rare lines of fish are affected. Here, the in vivo efficacy of two drug
candidates, tigecycline (1 MUg g-1 ) and clarithromycin (4 MUg g-1 ), was tested
in adult zebrafish experimentally infected with Mycobacterium chelonae. We
assessed both short (14 day)- and long-term (30 day) treatments and evaluated
fecundity and pathological endpoints. Fecundity and histology results show that
zebrafish tolerated antibiotics. Antibiotic treatments did not significantly
impact the prevalence of acid-fast granulomas; however, the severity of
infections (acid-fast granuloma intensity) was significantly decreased following
treatments.
PMID- 28422305
TI - New host record and molecular characterization of Dicauda atherinoidi Hoffman &
Walker (Bivalvulida: Myxobolidae): a parasite of the emerald shiner Notropis
atherinoides Rafinesque, 1818 and mimic shiner Notropis vollucellus Cope, 1865.
AB - Updated morphological and histopathological descriptions for Dicauda atherinoidi
(Bivalvulida:Myxobolidae) and an expanded host range are supplemented with the
first molecular data and phylogenetic analyses of the genus. Plasmodia were
located on the head, ventrum/body and fins of infected emerald shiner Notropis
atherinoides Rafinesque, 1818 and mimic shiner Notropis vollucellus Cope, 1865, a
new host species. Myxospores were spherical, ranging 9.3-11.4 MUm (10.5 +/- 0.4)
in length, 9.0-11.0 MUm (9.7 +/- 0.4) in width and 6.6-7.0 MUm (6.8 +/- 0.2)
thick in sutural view, and possessed 2-3 caudal processes (5.3-68.3 MUm, 31.1 +/-
13.6) connected to the spore body at the sutural groove, all of which are
consistent with the genus Dicauda. In the absence of available Dicauda sequence
data, the 18S rDNA sequences from Michigan isolates were most similar to
Myxobolus spp. Phylogenetic analyses clustered these isolates with myxobolid
species from cyprinid fish, suggesting these parasites may represent an
underpopulated group of cyprinid-infecting myxozoans. Histopathology revealed
thin-walled plasmodial pseudocysts in the dermis and associated connective
tissue, where granulomatous inflammation and focal scale atrophy were also
present. Further sampling/sequencing of myxobolids from Notropis spp. should
expand these underrepresented myxozoans and offer further insight into
Myxobolidae host family tropisms.
PMID- 28422307
TI - What is your diagnosis? Fine-needle aspirate of a lung nodule and bronchoalveolar
lavage from a dog.
PMID- 28422306
TI - Development of a novel frailty index to predict mortality in patients with end
stage liver disease.
AB - : Cirrhosis is characterized by muscle wasting, malnutrition, and functional
decline that confer excess mortality not well quantified by the Model for End
Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty
index to capture these extrahepatic complications of cirrhosis and enhance
mortality prediction in patients with cirrhosis. Consecutive outpatients listed
for liver transplantation at a single transplant center without MELD exceptions
were assessed with candidate frailty measures. Best subset selection analyses
with Cox regression identified subsets of frailty measures that predicted
waitlist mortality (=death or delisting because of sickness). We selected the
frailty index by balancing statistical accuracy with clinical utility. The net
reclassification index (NRI) evaluated the %patients correctly reclassified by
adding the frailty index to MELDNa. Included were 536 patients with cirrhosis
with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final
frailty index consisted of: grip strength, chair stands, and balance. The ability
of MELDNa and the frailty index to correctly rank patients according to their 3
month waitlist mortality risk (i.e., concordance-statistic) was 0.80 and 0.76,
respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa
alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P =
0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P <
0.001). Compared to those with robust frailty index scores (<20th percentile),
cirrhotics with poor frailty index scores (>80th percentile) were more impaired
by gait speed, difficulty with Instrumental Activities of Daily Living,
exhaustion, and low physical activity (P < 0.001 for each). CONCLUSION: Our
frailty index for patients with cirrhosis, comprised of three performance-based
metrics, has construct validity for the concept of frailty and improves risk
prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564-574).
PMID- 28422308
TI - Androgen receptor-regulated miRNA-193a-3p targets AJUBA to promote prostate
cancer cell migration.
AB - Background Dysregulation of microRNA (miRNA) expression is implicated in cancer
development and progression by modulating oncogenes or tumor suppressors at the
post-transcriptional level. Methods To investigate the role of miRNAs in prostate
cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in
androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate
cancer (CRPC) C4-2B cells. For functional validation, we specifically
investigated miR-193a-3p, which is highly upregulated in C4-2B cells and
modulated by the androgen receptor (AR). We elucidated the role of miR-193a-3p
and its downstream target gene in PCa cell migration using biochemical
approaches. Results We identified a subset of differentially expressed miRNAs in
C4-2B cells compared to LNCaP cells. Computational analysis shows that the
targets of upregulated miRNAs are significantly associated with downregulated
protein-coding mRNAs in C4-2B cells. Gene Ontology analysis further reveals that
these downregulated mRNAs are significantly enriched in cell-cell adhesion
functions. Downregulation of these miRNA-targeted genes may change PCa cell
motility resulting in the acquisition of metastatic potential. We then focus on
miR-193a-3p and demonstrate overexpression of miR-193a-3p increases cell
migration through downregulating its target AJUBA. AJUBA is a LIM domain protein
and contributes to the formation and stability of cadherin-mediated cell-cell
adhesion. Loss of AJUBA enhances PCa migration and downregulation of AJUBA
expression is observed in metastatic PCa tumors. Conclusions Our results suggest
a novel AR/miR-193a-3p/AJUBA pathway implicated in PCa progression. MiR-193a-3p
is a potential therapeutic target for metastatic PCa.
PMID- 28422309
TI - Necrotizing Sweet syndrome in a patient with myelodysplastic syndrome.
PMID- 28422311
TI - Reply.
PMID- 28422310
TI - Adult-onset cystic fibrosis liver disease: Diagnosis and characterization of an
underappreciated entity.
AB - : Cystic fibrosis (CF) liver disease (CFLD), a leading cause of death in CF, is
mostly described in pediatric populations. Adult-onset CFLD lacks sufficient
characterization and diagnostic tools. A cohort of CF patients without CFLD
during childhood were followed for up to 38 years with serologic testing,
imaging, and noninvasive fibrosis markers. Historical CFLD diagnostic criteria
were compared with newly proposed CFLD criteria. Thirty-six CF patients were
followed for a median of 24.5 years (interquartile range 15.6-32.9). By the last
follow-up, 11 (31%) had died. With conventional criteria, 8 (22%) patients had
CFLD; and by the new criteria, 17 (47%) had CFLD at a median age of 36.6 years
(interquartile range 26.5-43.2). By the new criteria, those with CFLD had higher
median alanine aminotransferase (42 versus 27, P = 0.005), aspartate
aminotransferase (AST; 26 versus 21, P = 0.01), direct bilirubin (0.13 versus
0.1, P = 0.01), prothrombin time (14.4 versus 12.4, P = 0.002), and AST-to
platelet ratio index (0.31 versus 0.23, P = 0.003) over the last 2 years of
follow-up. Subjects with a FibroScan >6.8 kPa had higher alanine aminotransferase
(42 versus 28U/L, P = 0.02), AST (35 versus 25U/L, P = 0.02), AST-to-platelet
ratio index (0.77 versus 0.25, P = 0.0004), and Fibrosis-4 index (2.14 versus
0.74, P = 0.0003) and lower platelet counts (205 versus 293, P = 0.02). One CFLD
patient had nodular regenerative hyperplasia. Longitudinally, mean platelet
counts significantly declined in the CFLD group (from 310 to 230 U/L, P =
0.0005). Deceased CFLD patients had lower platelet counts than those alive with
CFLD (143 versus 258 U/L, P = 0.004) or those deceased with no CFLD (143 versus
327U/L, P = 0.006). CONCLUSION: Adult-onset CFLD may be more prevalent than
previously described, which suggests a later wave of CFLD that impacts morbidity;
routine liver tests, radiologic imaging, noninvasive fibrosis markers, and
FibroScan can be used algorithmically to identify adult CFLD; and further
evaluation in other CF cohorts should be performed for validation. (Hepatology
2017;66:591-601).
PMID- 28422312
TI - What is your diagnosis? Cutaneous ulcerated nodule in a geriatric dog.
PMID- 28422313
TI - Regulome networks and mutational landscape in liver cancer: An informative path
to precision medicine.
PMID- 28422314
TI - Hepatic steatosis, hepatitis C, and human immunodeficiency viruses: A complex
interplay.
PMID- 28422315
TI - Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine
Arginine-Rich Protein ASF/SF2.
AB - Positive transcription elongation factor-b (P-TEFb) is required for the release
of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for
efficient proceeding to the transcription elongation. It consists of two core
subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is
the major and most studied combination. We have previously identified a novel
splice variant of cyclin T1, cyclin T1b, which negatively regulates the
transcription elongation of HIV-1 genes as well as several host genes. In this
study, we revealed the serine-arginine-rich protein, ASF/SF2, as a regulatory
factor of the alternative splicing of cyclin T1 gene. ASF/SF2 promotes the
production of cyclin T1b versus cyclin T1a and regulates the expression of cyclin
T1-depedent genes at the transcription level. We further found that a cis-element
on exon 8 is responsible for the skipping of exon 7 mediated by ASF/SF2.
Collectively, ASF/SF2 is identified as a splicing regulator of cyclin T1, which
contributes to the control of the subsequent transcription events. J. Cell.
Biochem. 118: 4020-4032, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422317
TI - A molecular mechanics and ab initio prediction of the 1 H chemical shifts of
pinanes.
AB - Molecular mechanics calculations plus the application of a refined Karplus
equation gave the conformations of 19 pinanes. These range from a Y-shaped
geometry in the apopinene and alpha-pinene series to a pseudo chair conformation
in beta-pinene, nopinone and verbanone, a flattened chair in pinocarvone and the
pinocarveols and a distorted Y shape for iso-verbanone. These structures were
then used as input to predict the 1 H chemical shifts of these compounds by semi
empirical (1 H-NMR spectra (HSPEC)) and ab initio gauge-invariant atomic orbital
(GIAO) calculations, the latter at the B3LYP hybrid density functional theory
level using 6-31++G** basis set. The two methods gave generally good agreement
with the 184 observed shifts with root mean square (RMS) errors 0.07 ppm (HSPEC)
and 0.10 ppm (GIAO), but the GIAO calculations gave several significant (>0.25
ppm) errors. One was for the H3 proton in apopinenone and other alpha,beta
unsaturated ketones; the others occurred for protons in close proximity to
hydroxyl groups. To provide more information, smaller analogues of known geometry
and chemical shifts were subject to the same analysis. In cyclopentenone, the
Gaussian geometry gave good agreement with the observed shifts, but the MMFF94,
MMX and MM3 geometries all gave errors for different protons. These results show
clearly that the molecular geometries of the alpha,beta unsaturated ketones are
responsible for the errors. The errors for the alcohols were examined using
ethanol as model and were shown to be due to the different possible conformations
of the OH group. Similar GIAO calculations on substituted methanes gave good
agreement for the methyl compounds but poor agreement for di and tri
halosubstituted methanes. The aforementioned method of molecular mechanics plus
GIAO calculations is shown to be a very useful tool for the investigation of
molecular geometries and conformations. However, multihalogen compounds may
require different basis sets for accurate calculations. Copyright (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28422318
TI - Computational Analysis of Breast Cancer GWAS Loci Identifies the Putative
Deleterious Effect of STXBP4 and ZNF404 Gene Variants.
AB - The genome-wide association studies (GWAS) have enabled us in identifying
different breast cancer (BC) susceptibility loci. However, majority of these are
non-coding variants with no annotated biological function. We investigated such
78 noncoding genome wide associated SNPs of BC and further expanded the list to
2,162 variants with strong linkage-disequilibrium (LD, r2 >=0.8). Using multiple
publically available algorithms such as CADD, GWAVA, and FATHAMM, we classified
all these variants into deleterious, damaging, or benign categories. Out of total
2,241 variants, 23 (1.02%) variants were extreme deleterious (rank 1), 70 (3.12%)
variants were deleterious (rank 2), and 1,937 (86.43%) variants were benign (rank
3). The results show 14% of lead or associated variants are under strong negative
selection (GERP++ RS >=2), and ~22% are under balancing selection (Tajima's D
score >2) in CEU population of 1KGP-the regions being positively selected (GERP++
RS <0) in mammalian evolution. The expression quantitative trait loci of highest
deleteriously ranked genes were tested on relevant adipose and breast tissues,
the results of which were extended for protein expression on breast tissues. From
the concordance analysis of ranking system of GWAVA, CADD, and FATHMM, eQTL and
protein expression, we identified the deleterious SNPs localized in STXBP4 and
ZNF404 genes which might play a role in BC development by dysregulating its gene
expression. This simple approach will be easier to implement and to prioritize
large scale GWAS data for variety of diseases and link to the potentially
unrecognized functional roles of genes. J. Cell. Biochem. 118: 4296-4307, 2017.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28422316
TI - Regulatory T cells: tolerance induction in solid organ transplantation.
AB - The concept of regulatory T cell (Treg ) therapy in transplantation is now a
reality. Significant advances in science and technology have enabled us to
isolate human Tregs , expand them to clinically relevant numbers and infuse them
into human transplant recipients. With several Phase I/II trials under way
investigating Treg safety and efficacy it is now more crucial than ever to
understand their complex biology. However, our journey is by no means complete;
results from these trials will undoubtedly provoke both further knowledge and
enquiry which, alongside evolving science, will continue to drive the
optimization of Treg therapy in the pursuit of transplantation tolerance. In this
review we will summarize current knowledge of Treg biology, explore novel
technologies in the setting of Treg immunotherapy and address key prerequisites
surrounding the clinical application of Tregs in transplantation.
PMID- 28422319
TI - Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery.
AB - Exosomes, the natural vehicles of intercellular communication, transfer proteins,
mRNAs, and microRNAs (miRNAs) and mediate many physiological and pathological
processes. It is not clear that whether exosomal miRNAs could regulate gene
expression across species, though some studies suggest interactions of exosomal
miRNAs between cells. In this report, we have isolated exosomes from rat PC12
cells and assessed their internalization by human cancer Hela cells. The
internalized exosomes were located in Hela lysosomes. Human PTEN expression was
significantly deregulated due to miR-21 delivered by rat cell exosomes. Our
results prove that exosomes could incorporate between cells of different species
and could regulate the protein expressions in the recipient cells by delivering
the enclosed miRNAs. Thus our study foreshadows a futuristic treatment approach
of utilizing miRNA enclosed exosome vehicles sans species concerns in combating
various diseases/ regulating abnormal proteins. J. Cell. Biochem. 118: 4267-4274,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422320
TI - miR-34b Modulates Skeletal Muscle Cell Proliferation and Differentiation.
AB - Myogenesis involves myoblast proliferation and differentiation to myocytes,
followed by fusion and hypertrophy to form myotubes during muscle development.
Increasing evidence showed that microRNAs (miRNAs) play important roles in the
regulation of myogenesis. We have previously revealed that miR-34b is steadily
increased during this process. This miRNA regulates differentiation in various
cell types, though its function in myogenesis remains to be elucidated. In this
study, we show that miR-34b represses muscle cell proliferation and promotes
myotube formation. Our quantitative iTRAQ-based proteomic analysis reveals 97
proteins are regulated by miR-34b in mouse myoblast C2C12. We identified that miR
34b targets 14-3-3 protein gamma, adenosylhomocysteinase and nucleolin by binding
to their 3'UTR. Further analysis of these proteins expression patterns show that
nucleolin is a cognate target of miR-34b during myogenic differentiation. Here,
we proved that a moderate reduction of nucleolin in cells enhanced the myotube
formation. However, nucleolin is required for myogenesis, as cells with low
levels of nucleolin reduced cell proliferation rate and are unable to
differentiate. Our data demonstrated that nucleolin regulates myogenesis in a
protein-abundance-dependent manner. J. Cell. Biochem. 118: 4285-4295, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28422321
TI - Aberrantly Expressed Long Non-Coding RNAs In CD8+ T Cells Response to Active
Tuberculosis.
AB - Dysregulated expression of long noncoding RNAs (lncRNAs) has been demonstrated as
being implicated in a variety of human diseases. In the study we aimed to
determine lncRNA profile in CD8+ T cells response to active tuberculosis (TB). We
examined the lncRNA expression by microarray in circulating CD8+ T cells isolated
from patients with active TB and healthy controls. Change predictions to analysis
was used to address functional roles of the deregulated mRNAs. Real-time
quantitative PCR (RT-qPCR) was used to validate the microarray result. In total,
328 lncRNAs and 356 mRNAs were differentially expressed in TB CD8+ T cells.
Upregulated mRNAs were mainly enriched in cAMP signaling pathway, calcium
signaling pathway, and TGF-beta signaling pathway, while downregulated mRNAs were
enriched in antigen processing and presentation and natural killer cell mediated
cytotoxicity in TB CD8+ T cells. Interestingly, we found that heme oxygenase 1
(HMOX1) was decreased in active TB CD8+ T cells, while its nearby lincRNA
XLOC_014219 was upregulated. Subsequent RT-qPCR results confirmed the changes.
This is the first research addressing lncRNA expression profiles in active TB
CD8+ T cells. The aberrantly expressed lncRNAs observed in the study may provide
clues to the dysfunction of CD8+ T cells and so to the pathophysiological
properties of active TB. Further studies should focus on the function of lncRNAs
involved in active TB. J. Cell. Biochem. 118: 4275-4284, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28422323
TI - Validating a Virtual Environment for Sexual Assault Victims.
AB - Virtual reality has shown promising results in the treatment of posttraumatic
stress disorder (PTSD) for some traumatic experiences, but sexual assault has
been understudied. One important question to address is the relevance and safety
of a virtual environment (VE) allowing patients to be progressively exposed to a
sexual assault scenario. The aim of this study was to validate such a VE. Thirty
women (victims and nonvictims of sexual assault) were randomly assigned in a
counter-balanced order to 2 immersions in a virtual bar: a control scenario where
the encounter with the aggressor does not lead to sexual assault and an
experimental scenario where the participant is assaulted. Immersions were
conducted in a fully immersive 6-wall system. Questionnaires were administered
and psychophysiological measures were recorded. No adverse events were reported
during or after the immersions. Repeated-measures analyses of covariance revealed
a significant time effect and significantly more anxiety (Cohen's f = 0.41, large
effect size) and negative affect (Cohen's f = 0.35, medium effect size) in the
experimental scenario than in the control condition. Given the safety of the
scenario and its potential to induce emotions, it can be further tested to
document its usefulness with sexual assault victims who suffer from PTSD.
PMID- 28422322
TI - Pentraxin-3 modulates lipopolysaccharide-induced inflammatory response and
attenuates liver injury.
AB - : Acute-on-chronic liver injury is characterized by an important inflammatory
response frequently associated with endotoxemia. In this context, acute-phase
proteins such as Pentraxin-3 (PTX3) are released; however, little is known about
their role in chronic liver disease. The aim of this study was to elucidate the
role of PTX3 in liver injury. The role of PTX3 was evaluated in cultured human
cells, liver tissue slices, and mice with acute-on-chronic liver injury. PTX3
expression was assessed in tissue and serum samples from 54 patients with
alcoholic hepatitis. PTX3 expression was up-regulated in animal models of liver
injury and strongly induced by lipopolysaccharide (LPS). Liver cell fractionation
showed that macrophages and activated hepatic stellate cells were the main cell
types expressing PTX3 in liver injury. Ex vivo and in vivo studies showed that
PTX3 treatment attenuated LPS-induced liver injury, inflammation, and cell
recruitment. Mechanistically, PTX3 mediated the hepatic stellate cell wound
healing response. Moreover, PTX3 modulated LPS-induced inflammation in human
primary liver macrophages and peripheral monocytes by enhancing a TIR domain
containing adapter-inducing interferon-dependent response and favoring a
macrophage interleukin-10-like phenotype. Additionally, hepatic and plasma PTX3
levels were increased in patients with alcoholic hepatitis, a prototypic acute-on
chronic condition; and its expression correlated with disease severity scores,
endotoxemia, infections, and short-term mortality, thus suggesting that
expression of PTX3 found in patients could be a counterregulatory response to
injury. CONCLUSION: Experimental and human evidence suggests that, in addition to
being a potential biomarker for alcoholic hepatitis, PTX3 participates in the
wound-healing response and attenuates LPS-induced liver injury and inflammation;
therefore, administration of PTX3 could be a promising therapeutic strategy in
acute-on-chronic conditions, particularly those associated with endotoxemia.
(Hepatology 2017;66:953-968).
PMID- 28422324
TI - Optical resolution and mechanism using enantioselective cellulose, sodium
alginate and hydroxypropyl-beta-cyclodextrin membranes.
AB - Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl-beta
cyclodextrin were prepared for chiral dialysis separations. After optimizing the
membrane material concentrations, the membrane preparation conditions and the
feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were
obtained for mandelic acid on the cellulose membrane, p-hydroxy phenylglycine on
the sodium alginate membrane, and p-hydroxy phenylglycine on the hydroxypropyl
beta-cyclodextrin membrane, respectively. To study the optical resolution
mechanism, chiral discrimination by membrane adsorption, solid phase extraction,
membrane chromatography, high-pressure liquid chromatography ultrafiltration were
performed. All of the experimental results showed that the first adsorbed
enantiomer was not the enantiomer that first permeated the membrane. The crystal
structures of mandelic acid and p-hydroxy phenylglycine are the racematic
compounds. We suggest that the chiral separation mechanism of the solid membrane
is "adsorption - association - diffusion," which is able to explain the optical
resolution of the enantioselective membrane. This is also the first report in
which solid membranes of sodium alginate and hydroxypropyl-beta-cyclodextrin were
used in the chiral separation of p-hydroxy phenylglycine.
PMID- 28422325
TI - The way forward in addressing abusive head trauma in infants - current
perspectives from Sweden.
PMID- 28422326
TI - Alveolar ridge dimensional changes following ridge preservation procedure with
novel devices: part 3 - histological analysis in non-human primate model.
AB - OBJECTIVES: This study sought to investigate the histological changes following
tooth extraction, ridge preservation and augmentation, using novel devices
designed to obturate the oral orifice of extraction sockets (SocketKAPTM) and
provide structural support for sockets with defective bony walls (SocketKAGETM)
in a non-human primate model. MATERIAL AND METHODS: Six Macaca fascicularis were
imaged by cone beam computed tomography to register their preoperative alveolar
bone. Three teeth were extracted in each animal, yielding intact socket walls and
were divided into three intervention groups: unassisted healing negative control
(Group A); SocketKAPTM (Group B); filled with anorganic bovine bone mineral
(ABBM) + SocketKAPTM (Group C). Three additional teeth were extracted in each
animal, followed by surgical resection of the entire buccal alveolar bone and
divided into three groups: negative control (Group D); SocketKAPTM + SocketKAGETM
(Group E); ABBM + SocketKAPTM + SocketKAGETM (Group F). Animals were euthanized
after 12 weeks, and treatment sites were examined by histology and
histomorphometric analysis. RESULTS: Control sockets with unassisted healing
(Groups A and D) underwent severe loss of bone width, height and total area
(approximately 40-60% loss). Application of SocketKAPTM in sites with intact
walls, as well as SocketKAPTM plus SocketKAGETM in sites with defective buccal
walls lead to higher preservation of alveolar bone height after 12 weeks post
intervention. Addition of ABBM leads to the highest degree of alveolar bone
dimensional preservation. Control sites with unassisted healing (Groups A and D),
as well as sites treated with extraction socket devices (Groups B and E) without
ABBM yielded higher percentage of vital bone, compared with sites filled with
ABBM (Groups C and F). No adverse histological responses were noted to
SocketKAPTM or SocketKAGETM devices. CONCLUSIONS: SocketKAPTM + SocketKAGETM
devices proved effective in reducing post-extraction alveolar bone resorption
mediating favorable wound healing within sockets. Addition of ABBM was associated
with reduced volumetric loss, although the bone fill was characterized by less
mature as well as more woven bone.
PMID- 28422328
TI - Synthesis of Benzo[c]silole Derivatives Bearing a Tetrasubstituted Exocyclic C=C
Double Bond by Palladium-Catalyzed Domino Reactions.
AB - The synthesis of diversely substituted 2,3-dihydro-benzo[c]siloles through an
unprecedented palladium-catalyzed domino sequence is reported, involving a
cyclocarbopalladation of an internal silylalkyne. This reaction proceeds with
complete stereoselectivity to lead to a fully substituted exocyclic C=C double
bond. Notably, the overall domino sequence appears to be crucial to obtain the
desired cyclic vinylsilanes.
PMID- 28422327
TI - Association between the ulcer status and the risk of delayed bleeding after the
endoscopic mucosal resection of colon.
AB - BACKGROUND AND AIM: Bleeding is the most common adverse event following
colonoscopic endoscopic mucosal resection (EMR). We aimed to assess the clinical
outcomes of a colon EMR according to the post-EMR ulcer status and determine the
risk factors of delayed postpolypectomy bleeding (DPPB) based on the post-EMR
ulcer status. METHODS: The medical records and endoscopic images of patients who
underwent EMR of colon polyps with diameters of >= 5 mm were retrospectively
reviewed by us. If any exposed vessels were observed on the post-EMR ulcer, the
types of exposed vessels were classified into cut and uncut vessels. The
coagulation injuries on the post-EMR ulcer were categorized as grades 1, 2, or 3.
RESULTS: In total, 505 patients with 728 polyps were examined. Exposed vessels
were present in 416 post-EMR ulcers, including cut vessels in 11 (1.5%) and uncut
vessels in 405 (55.6%). With regard to coagulation injury, 113 (15.5%), 443
(60.9%), and 172 (23.6%) post-EMR ulcers had grades 1, 2, and 3 injuries,
respectively. DPPB was observed in 20 lesions (2.7%). Multivariate analysis
indicated that a polyp size > 10 mm (odds ratio [OR], 3.354; 95% confidence
interval [CI], 1.229-9.154), cut vessels (OR, 18.913; 95% CI, 3.106-115.187), and
grade 3 coagulation injury (OR, 16.796; 95% CI, 1.825-154.556) were associated
with DPPB. CONCLUSIONS: Cut vessels and severe coagulation injury on post-EMR
ulcers, as well as larger polyp size, are risk factors for DPPB. Careful
inspection of post-EMR ulcers and prophylactic hemostasis, if necessary, may
improve the clinical outcomes of colonoscopic EMR.
PMID- 28422329
TI - Metal Complexes of a Redox-Active [1]Phosphaferrocenophane: Structures,
Electrochemistry and Redox-Induced Catalysis.
AB - The synthesis and characterisation of several metal complexes of a redox-active,
mesityl(Mes)-substituted [1]phosphaferrocenophane, FcPMes (1), are reported.
Cyclic voltammetry studies on the bimetallic complexes [M(kappa1 P-1)(cod)Cl]
(M=Rh: 2; M=Ir: 4), [Rh(kappa1 P-1)2 (CO)Cl] (3) and [AuCl(kappa1 P-1)] (5), in
conjunction with DFT calculations, provided indications for a good electronic
communication between the metal atoms. To confirm that the ferrocenophane unit
might be able to electrochemically influence the reactivity of the coordinated
transition metal, the rhodium complex 2 was employed as stimuli-responsive
catalyst in the hydrosilylation of terminal alkynes. All reactions were greatly
accelerated with in situ generated 2+ as a catalyst as compared to 2. Even more
importantly, a markedly different selectivity was observed. Both factors were
attributed to different mechanisms operating for 2 and 2+ (alternative Chalk
Harrod and Chalk-Harrod mechanism, respectively). DFT calculations revealed
relatively large differences for the activation barriers for 2 and 2+ in the
reductive elimination step of the classical Chalk-Harrod mechanism. Thus, the key
to the understanding is a cooperative "oxidatively induced reductive elimination"
step, which facilitates both a higher activity and a markedly different
selectivity.
PMID- 28422330
TI - Genetic relationships among female fertility disorders, female fertility traits
and productivity of Holstein dairy cows in the early lactation period.
AB - Fertility health disorders from the early lactation period including retained
placenta (REPLA), metritis (MET), corpus luteum persistence (CLP),
anoestria/acyclia (AOEAC) and ovarial cysts (OC), as well as overall disease
categories (disorders during the postpartal period (DPP), ovary infertility
(OINF), overall trait definition "fertility disorders" (FD)), were used to
estimate genetic (co)variance components with female fertility and test-day
traits. The disease data set comprised 25,142 Holstein cows from parities 1, 2
and 3 resulting in 43,584 lactations. For disease traits, we used the binary
trait definition (sick or healthy) and disease count data reflecting the sum of
treatments for the same disease within lactation or within lactation periods.
Statistical modelling included single and multiple trait repeatability animal
models for all trait combinations within a Bayesian framework. Heritabilities for
binary disease traits ranged from 0.04 (OC) to 0.10 (REPLA) and were slightly
lower for the corresponding sum trait definitions. Correlations between both
trait definitions were almost one, for genetic as well as for permanent
environmental effects. Moderate to high genetic correlations were found among
puerperal disorders DPP, REPLA and MET (0.45-0.98) and among the ovarian
disorders OINF, AOEAC, CLP and OC (0.59-0.99). Genetic correlations between
puerperal and ovarian disorders were close to zero, apart from the REPLA-OC
association (0.55). With regard to fertility disorders and productivity in early
lactation, a pronounced genetic antagonistic relationship was only identified
between OC and protein yield. Genetic correlations between fertility disorders
and test-day SCS were close to zero. OINF and all diseases contributing to OINF
were strongly correlated with the female fertility traits "interval from calving
to first service," "interval from service to pregnancy" and "interval from
calving to pregnancy." The strong correlations imply that fertility disorders
could be included in genetic evaluations of economic fertility traits as
correlated predictors. Vice versa, a breeding focus on female fertility traits
will reduce genetic susceptibility to OC, CLP and AOEAC.
PMID- 28422331
TI - A Metal-Free Oxidative Dehydrogenative Diels-Alder Reaction for Selective
Functionalization of Alkylbenzenes.
AB - Functionalization of C(sp3 )-H bonds under metal-free reaction conditions is a
great challenge due to poor bond reactivity. A novel metal-free oxidative
dehydrogenative Diels-Alder reaction of alkylbenzene derivatives with alkenes
through C(sp3 )-H bond functionalization is described. The developed oxidative
method provides a straightforward approach to biologically relevant 1,4
phenanthraquinone and isoindole derivatives from readily available starting
materials. Furthermore, the synthesis of nitrostyrenes from enylbenzene
derivatives by selective C(sp3 )-H bond functionalization has been demonstrated.
PMID- 28422332
TI - Biofilm dispersal: multiple elaborate strategies for dissemination of bacteria
with unique properties.
AB - In most environments, microorganisms evolve in a sessile mode of growth,
designated as biofilm, which is characterized by cells embedded in a self
produced extracellular matrix. Although a biofilm is commonly described as a
"cozy house" where resident bacteria are protected from aggression, bacteria are
able to break their biofilm bonds and escape to colonize new environments. This
regulated process is observed in a wide variety of species; it is referred to as
biofilm dispersal, and is triggered in response to various environmental and
biological signals. The first part of this review reports the main regulatory
mechanisms and effectors involved in biofilm dispersal. There is some evidence
that dispersal is a necessary step between the persistence of bacteria inside
biofilm and their dissemination. In the second part, an overview of the main
methods used so far to study the dispersal process and to harvest dispersed
bacteria was provided. Then focus was on the properties of the biofilm-dispersed
bacteria and the fundamental role of the dispersal process in pathogen
dissemination within a host organism. In light of the current body of knowledge,
it was suggested that dispersal acts as a potent means of disseminating bacteria
with enhanced colonization properties in the surrounding environment.
PMID- 28422333
TI - Assembling Porphyrins into Extended Network Structures by Employing Aromatic
Dicarboxylates: Synthesis, Metal Exchange, and Heterogeneous Catalytic Studies.
AB - Three new metal-organic porphyrinic framework compounds of zinc and 5,10,15,20
tetrakis(4-pyridyl)porphyrin (TPyP) have been synthesized under solvothermal
conditions. The compounds [Zn5 (C40 H24 N8 )(C8 H4 O4 )2 (NO3 )6 (DMA)2 ] (DMA)3
(H2 O)8 (1; DMA=dimethylacetamide), [Zn3 (C40 H24 N8 )(C8 H4 O4 )2 (DMF)](DMF)5
(H2 O)12 (2), and [Zn3 (C40 H24 N8 )(C12 H6 O4 )2 (DMA)2 ](H2 O)7 (3) have two
(1) and three dimensionally (2 and 3) extended structures. All the three
structures contain porphyrinic units connected through the carboxylate linkers.
The nitrates bind the metal centers and are not hydrogen bonded. The different
binding modes of nitrate in the structure of 1 are observed for the first time in
a porphyrin-based MOF. The openness of the structure allowed us to explore metal
exchange through a room-temperature metathetic route. Compound 2 undergoes 100 %
exchange with copper, whereas compound 3 exchanges 70 % with copper. The copper
exchanged compounds Cu?2 and Cu?3 were observed to be good heterogeneous
catalysts for many important organic reactions. The chemo and regioselective
enamination of beta-ketoesters, preparation of propargylamine derivatives as well
as regioselective cycloadditions of alkyne and azide (click reactions) have been
carried out with good yields and selectivity. All the compounds have been
characterized by PXRD, IR, UV/Vis, atomic absorption spectroscopy (AAS), and
energy-dispersive X-ray spectroscopy (for Cu exchange).
PMID- 28422334
TI - Polymer-Supported Palladium(II) Carbene Complexes: Catalytic Activity,
Recyclability, and Selectivity in C-H Acetoxylation of Arenes.
AB - Heterogeneous catalysts for selective oxidation of C-H bonds were synthesized by
co-polymerization of new N-heterocyclic carbene-palladium(II) (NHC-PdII )
monomers with divinylbenzene. The polymer-supported NHC-PdII -catalysed
undirected C-H acetoxylation of simple and methylated arenes as well as
polyarenes, with similar or superior efficiency compared to their homogeneous
analogues. In particular, the regioselectivity has been improved in the
acetoxylation of biphenyl and naphthalene compared to the best homogeneous
catalysts. The new polymer-supported catalysts maintain the original oxidation
state of PdII after repeated catalytic reactions, and exhibit no significant
leaching of palladium. In addition, the new catalysts have been successfully
recovered and reused without loss of activity over several cycles of reactions.
PMID- 28422335
TI - Effect of Isomeric Structures on Photovoltaic Performance of D-A Copolymers.
AB - Two donor-acceptor copolymers based on isomeric acceptor units, [7,7'
bithieno[2',3':4,5]thieno[2,3-d]thieno[3,2-b]pyridine]-5,5'(4H,4'H)-dione (BTTP)
and [2,2'-bithieno[2',3':4,5]thieno[2,3-d]thieno[3,2-b]pyridine]-5,5'(4H,4'H)
dione (iBTTP), are developed to study the effect of isomeric structures on
photovoltaic performance. Compared with PBDTBTTP, PBDTiBTTP possesses a smaller
bandgap for good light harvesting and a better pi-pi stacking for higher hole
mobility. PBDTiBTTP solar cells present balanced mobilities and good nanoscale
phase separation, giving a power conversion efficiency (PCE) of 6.51%, with
higher short-circuit current (Jsc ) and fill factor (FF).
PMID- 28422336
TI - A Designed ZnO@ZIF-8 Core-Shell Nanorod Film as a Gas Sensor with Excellent
Selectivity for H2 over CO.
AB - The development of H2 gas sensors is important for H2 production as a fuel. In
this work, a ZnO@ZIF-8 core-shell nanorod film is designed and synthesized as a
gas sensor through a facile solution deposition process. This film shows an
excellent selective response for H2 over CO. By fine-tuning the reaction
conditions, a ZnO@ZIF-8 core-shell structure with a thin, fine-grain, porous ZIF
8 shell is obtained. Owing to the facile H2 penetration through the ZIF-8 thin
shell (~110 nm) and the increased oxygen vacancies for the complex film, the
ZnO@ZIF-8 nanorod film shows a higher H2 sensitivity than a raw ZnO nanorod film.
More importantly, the ZnO@ZIF-8 nanorod film shows no response for CO at 200
degrees C. Because of the fine-grain confinement of the porous ZIF-8 shell (<140
nm), the molecular sieving effect is strengthened, which allows the effective
separation of H2 over CO. This work provides a promising strategy for the design
of high-performance H2 sensors.
PMID- 28422337
TI - In vivo validation of a novel algorithm for automatic premature ventricular
contractions recognition.
AB - INTRODUCTION: Template-matching algorithms are routinely used in the catheter
ablation of patients with premature ventricular contractions (PVCs). However,
systematic analysis of the accuracy and spatial resolution of such systems is
lacking. Therefore, the aim of this evaluation was to perform a systematic in
vivo validation of performance of a novel automated template-matching algorithm.
METHODS AND RESULTS: In a porcine model, paced beats simulating PVCs from
different origins were investigated. The ability to discriminate between sinus
rhythm and PVCs was tested by simulating PVCs using sequential pacing from
different cardiac chambers. The accuracy of the algorithm in correctly
classifying PVCs was reviewed by an independent investigator. In addition, the
spatial resolution of pace matching was evaluated by assessing the QRS morphology
discrimination at a distance of 0, 2, 4, and 6 mm of a simulated PVCs focus. The
specificity of the algorithm for recognizing simulated PVCs was 99.6% and the
sensitivity was 85.3%. There was a significant difference in the discrimination
metric discrimination metric (with 0% being a perfect match and 100% being no
correlation) between PVC origin (median 0%, interquartile range (IQR) 0-2%)
versus at 2 mm (5%, IQR 2-7%), 4 mm (16%, IQR 11-21%), and 6 mm (24%, IQR 19-28%,
P < 0.001 for all). The c-statistic for discrimination between PVC origin and a
distance >= 2 mm was 0.93. CONCLUSIONS: Automated template matching had high
specificity and sensitivity, with good spatial discrimination and a pace-mapping
resolution in range of 2 mm. Clinical application of this algorithm may assist in
the interventional treatment of patients with PVCs.
PMID- 28422338
TI - Arene-Inserted Extended Germa[n]pericyclynes: Synthesis, Structure, and
Phosphorescence Properties.
AB - This report describes the synthesis and characterization of arene-inserted
extended (ArEx) germa[n]pericyclynes composed of germanium and 1,4
diethynylbenzene units. These novel cyclic germanium-pi unit materials were
synthesized with diethynylbenzene and germanium dichloride. X-ray
crystallographic analysis revealed their structures, and the planar conformation
of ArEx germa[4]pericyclyne along with the regular aromatic rings. UV/Vis
absorption spectra and fluorescence emission spectra showed considerably unique
and highly improved character compared to previously reported
germa[n]pericyclynes. Even in the absence of transition metal components,
phosphorescence emissions were observed, and the emission lifetimes were
dramatically improved. ArEx germa[n]pericyclynes showed high photoluminescence
quantum yields, whereas low photoluminescence quantum yields were observed for
acyclic compounds. Density functional theory calculations show delocalized
orbitals between skipped alkyne units through a germanium tether, and an increase
in the HOMO energy level, leading to a small HOMO-LUMO energy gap.
PMID- 28422339
TI - Prenatal exposure to beta2-adrenoreceptor agonists and the risk of autism
spectrum disorders in offspring.
AB - PURPOSE: We aimed to examine the risk of autism spectrum disorders (ASDs) in the
offspring who were exposed to maternal use of beta2-adrenoreceptor agonist
(beta2AA) during pregnancy. METHODS: This is a population-based cohort study
including all live singleton births in Denmark from 1 January 1997 to 31 December
2008. Children born to mothers who used beta2AA during pregnancy were categorized
as exposed, and all other children were included in the unexposed group. Cases of
ASDs were identified from the Danish Psychiatric Central Register and the Danish
Patient Register. Incidence rate ratio (IRR) and 95% confidence interval were
estimated by Poisson regression models. RESULTS: Among 751 888 children in the
cohort, 9098 (1.21%) received a diagnosis of ASDs. We observed an increased risk
of ASDs in the exposed children (IRR = 1.28, 1.11-1.47), especially for those who
were exposed during the second trimester period (IRR = 1.38, 1.14-1.67). However,
when extending the exposure time window to 1 year prior to pregnancy, we observed
a similar association in children born to women who received beta2AA treatment
during pregnancy (IRR = 1.33, 1.11-1.59) to that in children born to women who
received beta2AA treatment 1 year prior to pregnancy (IRR = 1.35, 1.17-1.56).
CONCLUSION: Our finding suggested that children born to women who used beta2AA
during pregnancy have an increased risk of ASDs in later life, which is more
likely due to underlying maternal diseases rather than the exposure to beta2AA
itself. However, further study, which would better differentiate the effects
between indication and medicine, is needed to corroborate the finding. Copyright
(c) 2017 John Wiley & Sons, Ltd.
PMID- 28422340
TI - Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium
Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total
Synthesis.
AB - Four new macrolactones, leptolyngbyolides A-D, were isolated from the
cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar
structures of leptolyngbyolides were determined by extensive NMR studies,
although complete assignment of the absolute configuration awaited the catalytic
asymmetric total synthesis of leptolyngbyolide C. The synthesis took advantage of
the catalytic asymmetric thioamide-aldol reaction using copper(I) complexed with
a chiral bidentate phosphine ligand to regulate two key stereochemistries of the
molecule at the outset. The present total synthesis demonstrates the utility of
this reaction for the construction of complex chemical entities. In addition to
the total synthesis, this work reports that leptolyngbyolides depolymerize
filamentous actin (F-actin) both in vitro and in cells. Detailed biological
studies suggest the probable order of F-actin depolymerization and apoptosis
caused by leptolyngbyolides.
PMID- 28422341
TI - Late pubertal growth spurt in a girl with growth hormone deficiency: Is Kaufmann
therapy effective in a girl with short stature who responds poorly to growth
hormone therapy and estrogen-replacement therapy?
AB - A Japanese senior high school girl aged 18 years and 5 months with growth hormone
deficiency was referred for primary amenorrhea. Her height was 1.36 m, and her
bodyweight was 23.5 kg. She had received daily growth hormone therapy from the
age of 5 years. Growth hormone therapy was discontinued at the age of 16 years
and 11 months, and estrogen-replacement therapy (ERT) was started to stimulate
secondary sexual characteristics. Although ERT was performed until the age of 18
years and 11 months, genital bleeding did not occur. ERT was changed to Kaufmann
therapy, and the first genital bleeding occurred 1 year and 4 months later.
Finally, regular medically induced menses occurred at the age of 21 years and 10
months. Her height increased by 9 cm in 1 year after the initiation of menstrual
bleeding. Kaufmann therapy was associated not only with menstrual bleeding but
also with growth spurt.
PMID- 28422342
TI - The Development of Lingualized Occlusion.
AB - This article is a historical review of the development of the lingualized
occlusion concept over the past century. It focuses on the pioneers of
lingualized occlusion and their designs rather than on techniques for achieving a
lingualized complete denture occlusion.
PMID- 28422343
TI - E-MALDI: optimized conditions during electrowetting-enhanced drop drying for
MALDI-MS.
AB - We recently showed that electrowetting-enhanced sample preparation for MALDI-MS
(eMALDI) can increase the intensity of the MALDI signal by 2-25 times compared
with conventional drop drying by concentrating all the dried sample in a single
spot rather than leaving behind a heterogeneous coffee-stain pattern. Here, we
demonstrate that the eMALDI signal enhancement can be further increased to more
than 100 times by systematically optimizing the electrowetting actuation
frequency and amplitude. This enables 30 times signal increase for a peptide
standard. Simultaneously, drop drying times can be reduced approximately five
times by increasing the actuation voltage and/or decreasing the initial drop
volume. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28422344
TI - Use of blood pool agents with steady-state MRI to assess the vascular system.
AB - : Over the past two decades there have been significant advances in the use of
magnetic resonance imaging (MRI) to assess the vascular system. New imaging
sequences and improvements in magnet design have enabled the creation of higher
spatial resolution images. MRI is now a viable alternative imaging modality when
compared to both invasive angiography and computed tomographic angiography. The
use of blood pool agents has further facilitated the use of MR angiography (MRA);
their high molecular weight allows for lower doses of contrast medium
administration while their prolonged presence in the blood stream allows for
repeated high-quality volumetric imaging of both the arterial and venous
circulation. As such, MRA is now no longer constrained by the tight windows for
first-pass arterial and venous enhancement, which has resulted in the ability to
assess and diagnose a large range of vascular pathologies in both arterial and
venous systems. The intent of this review is to highlight MRI findings in common
vascular pathologies including peripheral arterial disease (PAD), abnormalities
of the abdominal aortic branches, postendovascular aortic aneurysm repair (EVAR)
endoleak assessment, popliteal artery entrapment syndrome (PAES), deep venous
thrombosis (DVT), vascular thoracic outlet syndrome (TOS), and vascular
malformations. In addition, the latest MRI techniques currently used to optimally
assess each of these pathologies will be discussed. LEVEL OF EVIDENCE: 5
Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;45:1559-1572.
PMID- 28422345
TI - Therapeutic Efficacy of Twin-Block and Fixed Oral Appliances in Patients with
Obstructive Sleep Apnea Syndrome.
AB - PURPOSE: To compare the efficacy of twin-block (i.e., allows mouth opening) and
fixed (i.e., maintains mouth closure) mandibular advancement splints (MASs) for
the treatment of obstructive sleep apnea-hypopnea syndrome (OSA). MATERIALS AND
METHODS: From 2011 to 2013, 23 patients with OSA in the twin-block group, and
from 2013 to 2015, 29 patients in the fixed MAS group were included. All patients
underwent polysomnography before and after 3 months of treatment. The two sets of
polysomnographic and cephalometric variables were compared. RESULTS: A
significant difference (p < 0.001) was observed in the apnea-hypopnea index
before and after MAS treatment in both groups (twin-block group: 20.6 +/- 11.5
vs. 14.7 +/- 9.4; fixed group: 21.4 +/- 15.2 vs. 11.2 +/- 9.7). In the twin-block
group, 5 patients (21.7%) were complete responders, 9 (39.1%) were fair
responders, and 9 (39.1%) were nonresponders; the corresponding figures for the
fixed group were 14 (48.3%), 9 (31.0%), and 6 (20.7%) patients. A significant
between-group difference was observed in the distribution of responders (p =
0.046). The fixed group showed a significant improvement in the snoring index (p
= 0.003), arousal index (p = 0.036), and desaturation rate (p = 0.012). Finally,
the change in incisal overjet was larger in the fixed group than in the twin
block group (p < 0.001). CONCLUSIONS: These results suggest that fixed oral
appliances are superior in treating OSA, based on their ability to prevent mouth
opening and reduce incisal overjet.
PMID- 28422346
TI - Does limb partitioning and positioning affect acute cardiorespiratory responses
during strength exercises in patients with COPD?
AB - BACKGROUND AND OBJECTIVE: Cardiorespiratory responses and symptoms in response to
endurance exercise in patients with COPD vary with the number and position of
involved limbs. Responses to such variations have never been quantified for
strength exercises. We therefore assessed acute cardiorespiratory responses
during brief bouts of weight lifting exercises. METHODS: We compared double-
versus single-limb leg extensions and arm elevations, as well as arm elevation
done above or below shoulder level in patients with moderate to severe COPD (n =
10, 6 males, 66 (8.1 years), forced expiratory volume on 1 s (FEV1 ) % predicted
= 34% (14%)). Minute ventilation, oxygen uptake, oxygen saturation, heart rate
(HR), blood pressure (BP), rate of perceived exertion (RPE) and recovery time
were collected during single sets of each exercise (10 repetitions at 80% of one
repetition maximum). RESULTS: Ventilatory and gas exchange responses were not
affected by the number of exercising limbs. Changes in HR, BP and RPE scores
during arm elevation above shoulder level were greater after double- compared
with single-arm elevation (P <= 0.001) and greater when exercising above compared
with below shoulder level (P <= 0.01). Double-arm elevation above shoulder level
required 1.5 min longer HR recovery time (P <= 0.041) compared with other
exercises. CONCLUSION: Double-arm elevation above shoulder level appears to be
more challenging than other strength exercise variations. Partitioning exercises
and limb position may reduce perceived exertion during training.
PMID- 28422347
TI - Serum placental growth factor and soluble fms-like tyrosine kinase 1 at mid
gestation in healthy women: Association with small-for-gestational-age neonates.
AB - AIM: This study was performed to determine the associations between serum
placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1)
levels at mid-gestation with the risk of small-for-gestational-age (SGA) neonates
born at gestational week (GW) >= 36 in healthy women. METHODS: PlGF and sFlt-1
concentrations were determined at GW 24-27 in 183 women with births at GW >= 36,
but without gestational diabetes mellitus and hypertension. RESULTS: Thirteen
(7.1%) SGA neonates were born. Median (range) GW at blood sampling was similar
between women with and without SGA (25 [24-25] and 24 [24-27], respectively, P =
0.671). Pre-pregnancy body mass index (BMI) and PlGF levels were significantly
lower in women with than without SGA, while sFlt-1 levels and sFlt-1 : PlGF ratio
(sFlt-1/PlGF) did not differ significantly between the two groups. PlGF and sFlt
1/PlGF, but not BMI or sFlt-1, showed significant correlations with birthweight z
score; the correlation was positive for PlGF and negative for sFlt-1/PlGF. Women
with PlGF level < 10th percentile and those with sFlt-1/PlGF level > 90th
percentile showed significantly increased risk of SGA compared to those with
respective counterpart characteristics; relative risk was 3.8 (95% confidence
interval, 1.3-11.3; 21% [4/19] vs 5.5% [9/164]) for PlGF and 7.9 (95% confidence
interval, 3.0-20.8, 33.3% [6/18] vs 4.2% [7/165]) for sFlt-1/PlGF. CONCLUSION:
Maternal PlGF and sFlt-1/PlGF determined during GW 24-27 were associated with the
risk of SGA neonates born at GW >= 36, even in women with uncomplicated
pregnancies.
PMID- 28422348
TI - Para-Hisian pacing maneuver: A pitfall in the pitfall.
PMID- 28422349
TI - Effects of extrinsic cardiac nerve stimulation on atrial fibrillation
inducibility: The regulatory role of the spinal cord.
AB - OBJECTIVE: To investigate the effect of the mutual regulation of the extrinsic
cardiac nerves on atrial electrophysiology and atrial fibrillation (AF)
vulnerability. METHODS AND RESULTS: Fourteen dogs were randomly divided into two
groups: spinal cord stimulation (SCS) group (n = 7) and spinal cord block (SCB)
group (n = 7). SCS was performed with 90% of the threshold voltage stimulating
the T1 -T2 spinal level, while SCB was performed by injecting 2% lidocaine into
the epidural space at the T2-3 level. The effective refractory period (ERP), ERP
dispersion, and AF inducibility were measured during atrial pacing combined with
different extrinsic cardiac nerve stimulation. ERPs were decreased in the atrium
and pulmonary veins and ERP dispersion was increased from baseline during left
cervical vagus nerve stimulation (VNS) or left stellate ganglion stimulation
(SGS) in the two groups. When combined with SCS, VNS resulted in diminished ERPs
at all recording sites, longer ERP dispersion and more episodes of AF than were
observed during VNS, whereas ERPs were greater and correspondingly fewer episodes
of AF occurred during SCS combined with SGS than SGS. In the SCB group, ERPs were
shortened, ERP dispersion was lengthened, and episodes of AF were increased
during SGS after SCB. SCS enhanced the activity of the left vagus nerve but
attenuated the left stellate ganglion and superior left ganglionated plexus.
CONCLUSION: SCS modulates extrinsic and intrinsic cardiac nerve activity among
the vagus nerve, stellate ganglion, and ganglionated plexus. SCS facilitates the
effect of VNS and attenuates the effect of SGS on atrial electrophysiology.
PMID- 28422350
TI - Electronic g Tensors in UV Complexes-A Computational Study.
AB - The theory and computation of EPR parameters from first principles has seen a
great deal of development over the past two decades. In particular, various
techniques for the computation of the electronic g tensor have been implemented
in many quantum chemistry packages. These methods have been successfully applied
to paramagnetic organic species and transition metal systems. The situation is
less well-understood and established in the case of actinide-containing molecules
and there is a dearth of experimental data available for validation of
computations. In this study quantum chemical techniques have been used to
evaluate the g tensor for UV complexes, for which experimental data are available
for comparison. The g tensors were calculated using relatively simple, state
averaged complete active space self-consistent field (SA-CASSCF) calculations.
This approach is shown to be capable of providing useful accuracy. Aspects of the
computations that should be refined to provide a more quantitative approach are
discussed. The key features of the underlying electronic structure that influence
the computed g values are delineated, providing a simple physical picture of
these subtle molecular properties.
PMID- 28422351
TI - Clinical phenotypes in asthma during childhood.
AB - Asthma is a heterogeneous disease characterized by numerous phenotypes relating
to age of onset, triggers, comorbidities, severity (assessed by multiple
exacerbations, lung function pattern) and finally the inflammatory cells involved
in the pathophysiologic pathway. These phenotypes can vary over time in relation
to changes in the principal triggers involved in the aetiology of the disease.
Nevertheless, in a patient with multiple allergies and early-onset disease
(defined as multiple sensitizations and allergic comorbidities), the prognosis of
asthma is poor with a high risk of persistence and severity of the disease during
childhood. Future research will focus on classifying phenotypes into groups based
on pathophysiologic mechanisms (endotypes) and the biomarkers attached to these
endotypes, which could predict prognosis and lead to targeted therapy. Currently,
these biomarkers are related to inflammatory cells associated with the asthma
endotype, essentially eosinophils and neutrophils (and related cytokines)
attached to Th-2 and non Th-1 pathways, respectively. The most severe asthma
(refractory asthma) is linked to neutrophil-derived inflammation (frequently
associated with female sex, obesity and possibly disorganized airway microbiota)
encountered in very young children or teenagers. Severe asthma is also linked to
or a marked eosinophil inflammatory process (frequently associated with multiple
atopy and, more rarely, with non-atopic hypereosinophilic asthma in children) and
frequently encountered in teenagers. Severe phenotypes of asthma could also play
a role in the origin of chronic obstructive pulmonary disease in adult life.
PMID- 28422353
TI - Comprehensive Review and Comparison of the Disinfection Techniques Currently
Available in the Literature.
AB - The goal of disinfection in the dental office is to prevent the spread of
infection from one patient to another and maintain the safety of the dental care
providers. Prevention of cross infection has significant effect on infection
control. The standard procedure of rinsing impressions under tap water
immediately after removal from the mouth eliminates microorganisms along with
saliva and blood. A broad search on published literature was done using the
keywords impression materials, disinfection method, and sterilization of dental
impression from 1980 to 2016 in Medline, Google Scholar, the internet, and
textbooks. This article critically analyzes the various published methods of
dental impression disinfection in dentistry.
PMID- 28422352
TI - Places and social contexts associated with simultaneous use of alcohol, tobacco
and marijuana among young adults.
AB - INTRODUCTION AND AIMS: Little is known about social-ecological correlates of
simultaneous use of alcohol with other substances. This study examined places and
social contexts associated with simultaneous use of alcohol, tobacco and
marijuana among young adults. DESIGN AND METHODS: We used survey data obtained
from 1538 young adult recent alcohol drinkers (49% male; 18-30 years old) in 24
non-contiguous cities in California. Event-level measures included alcohol,
tobacco and marijuana use, drinking places and social characteristics of the
event. Individual-level measures included alcohol expectancies, depression and
demographics. RESULTS: Bars and restaurants had less alcohol and marijuana use
(odds ratio = 0.34; 95% confidence interval 0.18, 0.62; P < 0.001) and alcohol,
marijuana and tobacco use (odds ratio = 0.27; 95% confidence interval 0.14, 0.54;
P < 0.001) compared with alcohol use only. Perceived percent of intoxicated
people at an event was associated with greater likelihood of using alcohol with
tobacco and marijuana at the event. At the individual level, greater age was
generally associated with increased odds of simultaneous use. Participants who
were male, less educated, more depressed and had positive alcohol expectancies
were more likely to simultaneously co-use alcohol with tobacco and marijuana.
Those with negative expectancies were less likely to simultaneously use these
substances. DISCUSSION AND CONCLUSIONS: Social events in private settings with a
high percentage of people who are intoxicated had increased likelihood of
simultaneous use of alcohol, tobacco and marijuana. Prevention efforts in these
settings may reduce simultaneous use of these substances and related harms.
[Lipperman-Kreda S, Paschall MJ, Saltz RF, Morrison CN. Places and social
contexts associated with simultaneous use of alcohol, tobacco and marijuana among
young adults. Drug Alcohol Rev 2017;00:000-000].
PMID- 28422354
TI - Auditory Verbal Experience and Agency in Waking, Sleep Onset, REM, and Non-REM
Sleep.
AB - We present one of the first quantitative studies on auditory verbal experiences
("hearing voices") and auditory verbal agency (inner speech, and specifically
"talking to (imaginary) voices or characters") in healthy participants across
states of consciousness. Tools of quantitative linguistic analysis were used to
measure participants' implicit knowledge of auditory verbal experiences (VE) and
auditory verbal agencies (VA), displayed in mentation reports from four different
states. Analysis was conducted on a total of 569 mentation reports from rapid eye
movement (REM) sleep, non-REM sleep, sleep onset, and waking. Physiology was
controlled with the nightcap sleep-wake mentation monitoring system. Sleep-onset
hallucinations, traditionally at the focus of scientific attention on auditory
verbal hallucinations, showed the lowest degree of VE and VA, whereas REM sleep
showed the highest degrees. Degrees of different linguistic-pragmatic aspects of
VE and VA likewise depend on the physiological states. The quantity and
pragmatics of VE and VA are a function of the physiologically distinct state of
consciousness in which they are conceived.
PMID- 28422355
TI - New insights into the morphogenesis of the gubernaculum testis and the inguinal
canal.
AB - There is no consensus about the role of the gubernaculum testis (GT). Nineteen
human embryos (Carnegie stages 15-23), 36 fetuses (9 weeks to term), and eight
neonates were examined. All the embryos and 25 fetuses (from weeks 9-16) were
processed for paraffin wax histology and serially sectioned at 10 um thickness.
The remaining 11 fetuses and the eight neonates were fresh specimens that were
dissected under a surgical microscope. The GT appeared during the embryonic
period (stages 17-23) with a horseshoe-shaped mesenchyme condensation of the
superior concavity, which was observed in four different topographical regions
sequentially through development. The GT was not attached at either of its ends
in any of the specimens, not to the gonad or in the scrotal sac. The inguinal
canal differentiates around the inguinal portion of the GT during the late
embryonic period. After stage 21, the GT appears enveloped by an evagination of
the peritoneal cavity. It has few striate muscular fibers and vessels. Although
the GT does not appear to have the role traditionally attributed to it, it is
still an essential structure and indirectly facilitates the descent of the
testes. It contributes to the formation of the inguinal canal and then forges the
pathway that the testes will subsequently take through the inguinal canal as they
migrate from the abdominal cavity into the scrotal sac. Clin. Anat. 30:599-607,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422356
TI - Bilateral femoral neck fractures resulting from pregnancy-associated osteoporosis
showed bone marrow edema on magnetic resonance imaging.
AB - Femoral neck fractures resulting from pregnancy-associated osteoporosis is a rare
condition. Herein, we report an undoubted case of pregnancy-associated
osteoporosis in a 38-year-old primiparous patient with pre-existing anorexia
nervosa who suffered bilateral femoral neck fractures in the third trimester and
early post-partum period. Magnetic resonance imaging revealed femoral neck
fractures as well as diffuse marrow edema involving both femoral heads, which are
considered under ordinary circumstances as characteristic imaging findings of
transient osteoporosis of the hip. Based on our experience, we propose that
pregnancy-associated osteoporosis might be present in femoral neck fractures
attributed to transient osteoporosis of the hip in pregnancy. Conversely, bone
status should be carefully and accurately estimated in cases of potential
transient osteoporosis of the hip in pregnancy to reduce future fracture risk.
PMID- 28422357
TI - Comparative analysis of the merino sheep and Iberian red deer abomasum during
prenatal development.
AB - The aim of this study is to describe differences in the ontogenesis of the
abomasum in sheep (domestic ruminant) and deer (wild ruminant). Histomorphometric
and immunohistochemical analysis were carried out on 50 embryos and fetuses of
the sheep and 50 red deer from the first prenatal stages until birth. To compare
similar periods of gestation in both species, we calculate the percentages of
gestation. The appearance of the abomasum was earlier in the red deer (22%
gestation) than in the sheep (25% gestation). Throughout development the
epithelium happened sequentially, being of the types pseudostratified to simple
cylindrical. This important modification was earlier in the red deer than the
sheep. At 46% gestation in red deer and 50% in sheep, gastric pits were observed
on the surface of abomasal folds. Our studies suggest a close link between the
initial formation of these pseudoglandular structures and the clear separation of
lamina propria and submucosa separated by de muscularis mucosae. At 54% gestation
in red deer and at 60% in sheep, in the bottom of these pits the first outlines
of glands were distinguishable. Finally, the presence of neuroendocrine and glial
cells were detected in deer at earlier stages than in sheep.
PMID- 28422358
TI - Is mean platelet volume a better biomarker in pre-eclampsia?
AB - AIM: Platelet activation and destruction is a well recognized feature of pre
eclampsia, but the current literature is contradictory regarding the role of mean
platelet volume (MPV) in the diagnosis of this condition. We investigated whether
MPV, compared with other routine laboratory markers such as platelet count, is a
more significant biomarker of pre-eclampsia, giving special attention to the
intrapartum period. METHODS: Biochemical and hematological markers along
pregnancy including MPV were compared retrospectively between pre-eclampsia and
matched controls. Laboratory marker data were compared using independent t-test.
A logistic regression model was used to compare the strength of the associations
of MPV and other routine markers such as platelet count with pre-eclampsia.
Receiver operating characteristic curves were plotted. RESULTS: There were a
total of 150 cases of pre-eclampsia and 297 controls. In the pre-eclampsia group,
there were 60 cases of mild pre-eclampsia (40.0%); 84, severe (56.0%); and six of
eclampsia (4.0%). MPV was significantly higher in the pre-eclampsia than in the
control group (11.3 +/- 1.0 vs 10.1 +/- 0.8 fL, P = 0.002). On multivariate
analysis, MPV was the only statistically significant biomarker of pre-eclampsia
(OR, 4.5; 95%CI: 1.5-13.7), and severe pre-eclampsia (OR, 6.2; 95%CI: 1.6-24.6);
performing superiorly to platelet count. CONCLUSIONS: Mean platelet volume is a
more significant biomarker of pre-eclampsia. It is more significantly associated
with this condition than other routinely measured laboratory markers such as
platelet count. MPV is routinely obtained on complete blood cell count and its
utilization in the assessment of pre-eclampsia in a clinical setting should
continue to be evaluated.
PMID- 28422359
TI - Clinical Evaluation of Indirect Particle-Filled Composite Resin CAD/CAM Partial
Crowns after 24 Months.
AB - PURPOSE: Resin-based CAD/CAM compound materials might be promising for single
tooth restorations. Insufficient clinical data are available for this new
material class. The purpose of this study was to describe initial clinical in
vivo results for indirect particle-filled composite resin CAD/CAM restorations
after 24 months. MATERIALS AND METHODS: Indirect particle-filled composite resin
restorations were fabricated with a CAD/CAM method (CEREC Bluecam intraoral
scanner, CEREC MCXL milling unit) by calibrated dental students. Forty-two
partial crown restorations were seated adhesively in 30 patients with caries
lesions or insufficient restorations (baseline). Strict inclusion criteria were
defined for the patient collective. Follow-up evaluation comprised 40
restorations after 12 months and 33 restorations after 24 months. Evaluation
criteria were modified FDI criteria with grades (1) to (5). Rating with FDI
criteria (5) was defined as clinical failure. Statistical analysis was performed
with Wilcoxon-Test (p < 0.05). RESULTS: The success rate of indirect particle
filled composite resin CAD/CAM restorations after 12 months was 95.0% with two
debondings observed. The cumulative success rate for indirect particle-filled
composite resin CAD/CAM restorations after 24 months was 85.7% with two tooth
fractures and one debonding. Statistically significant differences were found for
baseline and 24-month follow-up evaluation for anatomic form and marginal
adaptation criterion examined in respect to FDI criteria guidelines (Wilcoxon
Test, p < 0.05). CONCLUSIONS: This study demonstrates particle-filled composite
resin CAD/CAM restorations having a clinical success rate of 85.7% after 24
months. Adhesive bonding procedures need to be ensured carefully. A longer
clinical evaluation period is necessary to draw further conclusions.
PMID- 28422360
TI - Photoinduced Iron-Based Water-Induced Phase Separable Catalysis (WPSC) ICAR ATRP
of Poly(ethylene glycol) Methyl Ether Methacrylate.
AB - Iron-mediated atom transfer radical polymerization (ATRP) has gained extensive
attention because of the superiority of iron catalysts, such as low toxicity,
abundant reserves, and good biocompatibility. Herein, a practical iron catalyst
recycling system, photoinduced iron-based water-induced phase separable catalysis
ATRP with initiators for continuous activator regeneration, at room temperature
is developed for the first time. In this polymerization system, the
polymerization is conducted in homogenous solvents consisting of p-xylene and
ethanol, using commercially available 5,10,15,20-tetraphenyl-21H,23H-porphine
iron(III) chloride as the iron catalyst, ethyl 2-bromophenylacetate as the ATRP
initiator, 2,4,6-trimethylbenzoyl diphenylphosphine oxide as the photoinitiator,
and poly(ethylene glycol) methyl ether methacrylate as the model hydrophilic
monomer. After polymerization, a certain amount of water is added to induce the
phase separation so that the catalyst can be separated and recycled in p-xylene
phase with very low residual metal complexes (<12 ppm) in the resultant polymers
even after six times recycle experiments.
PMID- 28422361
TI - Risks of thromboembolism associated with hormone contraceptives in Japanese
compared with Western women.
AB - We extracted 581 thromboembolic events associated with combined oral
contraceptives (COC) that occurred between 2004 and 2013 in Japan, from the
Pharmaceuticals and Medical Devices Agency database. The most common
thromboembolic events associated with COC were deep vein thrombosis, pulmonary
embolism and their combination. The reported thromboembolic events increased year
by year, in association with an increase in the quantity of prescribed low-dose
estrogen progestin after approval for health insurance coverage for dysmenorrhea
in 2008 in Japan. The incidence of venous thromboembolism (VTE) in Japanese COC
users is estimated to be lower compared with their Western counterparts. In
contrast, the frequency of all thromboembolic events peaked at 90 days from the
start of COC, as in Western studies. The risk of VTE in the overweight group
(body mass index >= 25 kg/m2 ) was more than twofold higher than in the standard
group, and age-specific incidence rate rose sharply after the age of 40. There
were different VTE risks according to progestin type in Japan as in Western
countries, but a definite conclusion about risk according to progestin type was
not able to be reached at present. As for the risk of arterial embolism and
thrombosis, the difference by progestin type was small, but it became higher at
>=50 years of age. Last, mortality rate caused by thromboembolism is extremely
low among COC users.
PMID- 28422362
TI - Ultrasound diagnosis of intramural pregnancy.
AB - Intramural pregnancy is a rare type of ectopic pregnancy, where the gestational
sac is implanted inside the myometrium instead of the endometrial and fallopian
tubes. Preoperative diagnosis remains very difficult. Ultrasonic findings vary
according to the anatomical location or duration of pregnancy. In this study, we
summarized the ultrasonic characteristics of intramural pregnancy by assessing
three cases. We also propose a set of ultrasonic characteristics to facilitate
differential diagnosis between intramural pregnancy and other types of ectopic
pregnancy.
PMID- 28422363
TI - The occhiolino (occ) mutant Zebrafish, a model for development of the optical
function in the biological lens.
AB - BACKGROUND: Zebrafish visual function depends on quality optics. An F3 screen for
developmental mutations in the Zebrafish nervous system was conducted in wild
type (wt) AB Zebrafish exposed to 3 mM of N-ethyl-N-nitrosourea (ENU). RESULTS:
Mutant offspring, identified in an F3 screen, were characterized by a small
pupil, resulting from retinal hypertrophy or hyperplasia and a small lens.
Deficits in visual function made feeding difficult after hatching at
approximately 5-6 days postfertilization (dpf). Special feeding conditions were
necessary for survival of the occhiolino (occ) mutants after 6 dpf. Optokinetic
response (OKR) tests measured defects in visual function in the occ mutant,
although electroretinograms (ERGs) were normal in the mutant and wt. Consistent
with the ERGs, histology found normal retinal structure in the occ mutant and wt
Zebrafish. However, lens development was abnormal. Multiphoton imaging of the
developmental stages of live embryos confirmed the formation of a secondary mass
of lens cells in the developing eye of the mutant Zebrafish at 3-4 dpf, and
laminin immunohistochemistry indicated the lens capsule was thin and disorganized
in the mutant Zebrafish. CONCLUSIONS: The occ Zebrafish is a novel disease model
for visual defects associated with abnormal lens development. Developmental
Dynamics 246:915-924, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422364
TI - Novel technique for adhesion barrier insertion by using cut-off surgical glove
fingers in laparoscopic surgery.
AB - AIM: Laparoscopic surgery causes fewer postoperative adhesions than laparotomy
and adhesion barriers are used to lessen the chance of adhesion. Sodium
hyaluronate and carboxymethylcellulose (SH-CMC), a bioresorbable membrane, is
effective in preventing adhesions. However, its properties make it difficult to
insert the film into the abdominal cavity and to place it into the target area
during laparoscopic surgeries. Here we report a novel technique for applying SH
CMC during laparoscopic surgeries by using cut-off surgical glove fingers.
METHODS: In our dry-box experiment, we found that SH-CMC became more flexible
after moisturizing for 30 s. Therefore, for this procedure, we moisturizing both
sides of the SH-CMC sheet (7.35 * 6.35 cm) on wet gauze (for 30 s). The film was
rolled into cut-off surgical glove fingers and inserted into the abdominal cavity
through a 12-mm trocar. The film was then removed from the glove finger and
unrolled onto the target area (glove-finger method). RESULTS: The dry-box
experiment revealed that moisturizing both sides of SH-CMC for 30 s/side, 15 min
after package removal, made the film more flexible. Ninety of 96 attempts with SH
CMC were successful among the 24 patients who underwent total laparoscopic
hysterectomy with our glove-finger method. CONCLUSION: Our glove-finger method
can realize the smooth application of SH-CMC to the target area during
laparoscopic surgeries.
PMID- 28422365
TI - Successful vaginal delivery at term after vaginal reconstruction with labium
minus flaps in a patient with vaginal atresia: A rare case report.
AB - We report a case of successful vaginal delivery after vaginal reconstruction with
labium minus flaps in a 23-year-old patient with congenital vaginal atresia. The
patient primarily presented with amenorrhea and cyclic abdominal pain;
transabdominal ultrasonography revealed an enlarged uterus due to hematometra and
absence of the lower segment of the vagina. Eight years ago, she had undergone an
unsuccessful attempt at canalization at a local hospital. Upon referral to our
hospital, she underwent vaginal reconstruction with labium minus flaps. Four
months after this procedure, she became pregnant and, subsequently, successfully
and safely vaginally delivered a healthy female baby weighing 3250 g at 38+1
weeks' gestation. The delivery did not involve perineal laceration by lateral
episiotomy. To the best of our knowledge, this is the first reported case of
successful vaginal delivery at term after vaginal reconstruction with labium
minus flaps in a patient with vaginal atresia.
PMID- 28422366
TI - Oral paracoccidioidomycosis: Retrospective analysis of 55 Brazilian patients.
AB - Paracoccidioidomycosis (PCM) is a rare fungal infection in the world, but endemic
and acquired exclusively in Latin America, with the highest prevalence in South
America and Brazil, particularly. Changes in oral cavity are common and
constitute the first clinical manifestation in many patients. The aim of this
study was to describe the prevalence of oral PCM and analyse the profile of the
disease and patients. Retrospective research, consisting of information present
in the medical records in the period 1998-2015, whose histopathological diagnosis
was oral PCM. Fifty-five oral PCM cases were confirmed. Of these patients, 90.9%
were males and 9.1% were females. The average age was 49.66 years and the most
reported occupation was rural workers. The painful symptomatology was present in
61.82% of patients. Erythematous lesions were predominant in 73% of them. In
single lesions (22 cases), the most common locations were jugal mucosa and
tongue. In multiple involvement (30 cases), the most affected regions were lips,
jugal mucosa and alveolar ridge. Epidemiology of PCM, was similar to several
other studies, especially in Brazil. This is the most important fungal infection
in Latin America and the recognition of oral lesions is extremely important, as
is often the first and in many cases the only manifestation of the disease.
PMID- 28422367
TI - Microtensile Bond Strength of a Resin Cement to Silica-Based and Y-TZP Ceramics
Using Different Surface Treatments.
AB - PURPOSE: To evaluate the effects of different surface treatments on the
microtensile bond strength (MUTBS) of bonding between resin cement and lithia or
zirconia-based ceramics using an in vitro study. MATERIALS AND METHODS: Three
zirconia ceramic blocks (IPS e.max ZirCAD) and three lithium disilicate ceramic
blocks (IPS e.max CAD) were sintered and duplicated in resin composite. The
zirconia specimens underwent various treatments (n = 1): (i) Sandblast + primer
(ZiSa); (ii) sandblast + laser irradiation + primer (ZiSaLa); or (iii) laser
irradiation + primer (ZiLa). The lithium disilicate specimens also underwent
various treatments: (i) sandblast + HF + silane (LiSaE); (ii) sandblast + silane
(LiSa); or (iii) sandblast + laser irradiation + silane (LiSaLa). The ceramic
composite blocks were cemented with resin cement and cut to produce bars with
approx. 1 mm2 bonding areas. The specimens were thermocycled, and bond strength
tests were performed in a universal testing machine. The fracture type was
determined by observing the fractured surface under a stereomicroscope. The mean
bond strengths of the specimens were statistically analyzed using one-way ANOVA
and Duncan's tests (alpha = 0.05). RESULTS: Mean comparison of the MUTBS showed
no significant difference between LiSaE and LiSa (p > 0.05), but significant
differences between LiSaE and other groups (p <= 0.01). No significant
differences were found between the ZiSaLa and ZiSa groups (p > 0.05). The modes
of failure in all groups were mostly adhesive (57% to 80%). The mean bond
strengths in laser-irradiated ceramics were significantly lower than those from
other surface treatments. All ZiLa specimens debonded before testing (pretest
failure). CONCLUSIONS: Lithium disilicate ceramic surface treated with a
combination of sandblasting and silane application provided a bond strength
comparable to that provided by sandblasting in combination with acid etching and
applying silane. Groups treated with laser irradiation had significantly lower
bond strengths than other groups.
PMID- 28422368
TI - Safety and efficacy of pulmonary vein isolation using a surround flow catheter
with contact force measurement capabilities: A multicenter registry.
AB - INTRODUCTION: Pulmonary vein (PV) isolation is the cornerstone of catheter
ablation in patients with atrial fibrillation (AF). Surround flow and contact
force (CF) measurement capabilities might enhance procedure efficacy and safety.
We report on the safety and midterm efficacy of a novel ablation catheter for PV
isolation in patients with AF. METHODS AND RESULTS: Two hundred thirty-three
consecutive patients (57 +/- 11 years, 76% males, 51% with structural heart
disease), referred for paroxysmal (157) or persistent (76) AF, underwent PV
isolation by a surround flow catheter with CF measurement capability in four
centers. Ablation was guided by electroanatomic mapping allowing radiofrequency
(RF) energy delivery in the antral region aiming at PV isolation. Mean overall
procedure time was 100 +/- 42 minutes with a mean fluoroscopy time of 6 +/- 5
minutes. Mean ablation time was 31+/-15 minutes; 99% of the targeted veins were
isolated. The mean CF value during ablation was 13 +/- 4 g. Intraprocedural early
(30 minutes) PV reconnection occurred in 12% PVs, and all PVs were effectively
reisolated. One pericardial effusion and five groin hematomas were reported.
During a mean follow-up of 12 +/- 6 months, 30 (12.9%) (10% paroxysmal AF vs. 18%
persistent AF, P = 0.07) patients had an atrial arrhythmias recurrence.
CONCLUSIONS: In this multicenter registry, RF ablation using a new surround flow
catheter, with CF sensor, resulted as feasible, achieving a high rate of isolated
PVs. Procedural and fluoroscopy times and success rates were comparable with
other techniques with a low complication rate.
PMID- 28422369
TI - What impact do questionnaire length and monetary incentives have on mailed health
psychology survey response?
AB - OBJECTIVES: Response rates to health-related surveys are declining. This study
tested two strategies to improve the response rate to a health psychology survey
mailed through English general practices: (1) sending a shortened questionnaire
and (2) offering a monetary incentive to return a completed questionnaire.
DESIGN: Randomized controlled trial. METHODS: Adults (n = 4,241) aged 45-59
years, from four General Practices in South-East England, were mailed a survey on
attitudes towards bowel cancer screening. Using a 2 * 4 factorial design,
participants were randomized to receive a 'short' (four A4 pages) or a 'long'
(seven A4 pages) questionnaire, and one of four monetary incentives to return a
completed questionnaire - (1) no monetary incentive, (2) L2.50 shop voucher, (3)
L5.00 shop voucher, and (4) inclusion in a L250 shop voucher prize draw. Age,
gender, and area-level deprivation were obtained from the General Practices.
RESULTS: The overall response rate was 41% (n = 1,589). Response to the 'short'
questionnaire (42%) was not significantly different from the 'long' questionnaire
(40%). The L2.50 incentive (43%) significantly improved response rates in
univariate analyses, and remained significant after controlling for age, gender,
area-level deprivation, and questionnaire length. The L5.00 (42%) and L250 prize
draw (41%) incentives had no significant impact on response rates compared to no
incentive (38%). CONCLUSIONS: A small monetary incentive (L2.50) may slightly
increase response to a mailed health psychology survey. The length of the
questionnaire (four pages vs. seven pages) did not influence response. Although
frequently used, entry into a prize draw did not increase response. Achieving
representative samples remains a challenge for health psychology. Statement of
contribution What is already known on this subject Response rates to mailed
questionnaires continue to decline, threatening the representativeness of data.
Prize draw incentives are frequently used but there is little evidence to support
their efficacy. Research on interactions between incentives, questionnaire
length, and demographics is lacking. What does this study add Contrary to
previous findings, questionnaire length did not influence response rate. A L2.50
incentive increased response, while incentives of L5.00 and a L250 prize draw did
not. Achieving representative samples to questionnaires remains a challenge for
health psychology.
PMID- 28422370
TI - Leisure riding horses: research topics versus the needs of stakeholders.
AB - Horses intended for leisure riding do not undergo any selection and most often
retired sports horses or defective horses are chosen, as a low selling price
determines their purchase by a leisure riding center. Unfortunately, horses
bought at low prices usually have low utility value, are difficult to handle,
require a special or individual approach and do not provide satisfaction in
riding. However, neither modern horse breeding nor scientific research address
the need to breed horses for leisure activities. There is no clear definition of
a model leisure horse and criteria or information for its selection are not
readily available in scientific publications. A wide spectrum of research methods
may be used to evaluate various performance traits in horses intended for leisure
activities. The fact that the population of recreational horses and their riders
outnumber sporting horses should attract the special attention of scientific
research. Their utility traits need to be determined with modern technology and
methods in the same way they are for sporting horses. Such a system of evaluation
would be very helpful for riders.
PMID- 28422372
TI - Effect of urine creatinine level during pregnancy on dipstick test.
AB - AIM: Dipstick results for proteinuria are affected by urine concentration, and
thus urine creatinine concentration ([Cr]). This study was performed to determine
whether spot urine [Cr] changes significantly during pregnancy, leading to a
significantly different false-negative rate (FNR) on dipstick test between
trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in
631 spot urine samples with negative/equivocal dipstick from 425 pregnant women.
False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg.
RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3
477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n
= 344), and third (n = 191) trimester urine samples, respectively (P = 0.000,
Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing
gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than
that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third
trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was
47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute
urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining
611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046).
CONCLUSIONS: Urine samples in the second and third trimesters were more likely to
be diluted compared with the first trimester. This was associated with high FNR
in third trimester urine samples.
PMID- 28422371
TI - Effects of M1 and M4 activation on excitatory synaptic transmission in CA1.
AB - Hippocampal networks are particularly susceptible to dysfunction in many
neurodegenerative diseases and neuropsychiatric disorders including Alzheimer's
disease, Lewy body dementia, and schizophrenia. CA1, a major output region of the
hippocampus, receives glutamatergic input from both hippocampal CA3 and
entorhinal cortex, via the Schaffer collateral (SC) and temporoammonic (TA)
pathways, respectively. SC and TA inputs to CA1 are thought to be differentially
involved in the retrieval of previously stored memories versus the encoding of
novel information, and switching between these two crucial hippocampal functions
is thought to critically depend on acetylcholine (ACh) acting at muscarinic
receptors. In this study, we aimed to determine the roles of specific subtypes of
muscarinic receptors in mediating the neuromodulatory effects of ACh on
glutamatergic synaptic transmission in the SC and TA pathways of CA1. Using
selective pharmacological activation of M1 or M4 receptors along with
extracellular and intracellular electrophysiology recordings from adult rat
hippocampal slices, we demonstrate that activation of M1 receptors increases
spontaneous spike rates of neuronal ensembles in CA1 and increases the intrinsic
excitability of pyramidal neurons and interneurons. Selective activation of M4
receptors inhibits glutamate release in the SC pathway, while leaving synaptic
transmission in the TA pathway comparatively intact. These results suggest
specific mechanisms by which M1 and M4 activation may normalize CA1 circuit
activity following disruptions of signaling that accompany neurodegenerative
dementias or neuropsychiatric disorders. These findings are of particular
interest in light of clinical findings that xanomeline, an M1/M4 preferring
agonist, was able to improve cognitive and behavioral symptoms in patients with
Alzheimer's disease or schizophrenia.
PMID- 28422373
TI - Longitudinal recovery of local neuronal activity and consciousness level in
acquired brain injury.
AB - Decreased brain activity in the default mode network, particularly in the
precuneus (PCU), has been consistently shown in acquired brain injury (ABI)
patients. However, it is unclear whether resting-state brain activity recovers
longitudinally in ABI patients and whether functional activity restoration is
associated with improvements in consciousness level. Here, resting-state fMRI
data were acquired from 23 ABI patients and 30 age- and gender-matched controls
with two longitudinal observations for each participant. The fMRI data were
analyzed using amplitude of low-frequency fluctuation (ALFF) to measure the
fluctuation strength of local spontaneous activity, and seed-based functional
connectivity was used to measure functional relationship with the seed region in
the whole brain. The level of consciousness was assessed using the Glasgow Coma
Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) on both scanning days of the
patients. Interaction effect between the two groups and two scans in ALFF was
observed in the PCU, which was driven by restored ALFF in the ABI, while a stable
ALFF in the control group. Moreover, restoration of ALFF in the PCU correlated
with improvements in both the CRS-R and GCS. Specifically, recovery of ALFF in
the PCU primarily reflected the signals of the slow-4 frequency band (0.027-0.073
Hz). Based on the functional connectivity maps of the PCU, we observed a
nonsignificant interaction effect or correlation with consciousness level. These
findings suggest local activity in the PCU but possibly not its functional
connectivity, is related to the longitudinal changes in behavioral responsiveness
in ABI. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422374
TI - Significant curative functions of the mesenchymal stem cells on methotrexate
induced kidney and liver injuries in rats.
AB - Mesenchymal stem cells (MSCs) curative effects on methotrexate (MTX)-induced
kidney and liver injuries remain elusive. Therefore, rats were divided into five
groups, rats received MTX orally (14 mg/kg) as a single dose/week for 2 weeks,
groups 3 and 4 were injected once with 2 * 106 cells bone marrow MSCs and adipose
derived MSCs, respectively. The last group administered dexamethasone (DEX) (0.5
mg/kg, p.o) for 7 days. MTX caused marked increase in malondialdehyde and
nitrite/nitrate concentrations. However, MTX administration decreased reduced
glutathione content plus catalase activity. In addition, MTX caused a significant
increment in kidney and liver biomarkers levels. Moreover, MTX showed renal
tubules vacuolation and necrosis of hepatocytes, as well expression of caspase-3
and nuclear factor kappa beta in kidney and liver tissues were observed. MSCs
treatment alleviated previous side effects induced by MTX. MSCs improved
nephrotoxicity and hepatotoxicity induced by MTX to a better extent as compared
with DEX.
PMID- 28422375
TI - Recurrent ovarian undifferentiated carcinoma resembling hepatoid morphology
treated with pegylated liposomal doxorubicin and bevacizumab.
AB - Hepatoid carcinomas are undifferentiated epithelial carcinomas that are
pathologically similar to hepatocellular carcinoma, but occur in a variety of
organs. Hepatoid carcinomas, as strictly defined, typically produce alpha
fetoprotein. In addition, a standard effective chemotherapy regimen for hepatoid
carcinoma has yet to be established. We present a case of advanced primary
ovarian cancer that was pathologically similar to hepatoid carcinoma without
staining for alpha-fetoprotein or hepatocyte paraffin 1. The primary ovarian,
metastatic, and recurrent tumors shared similar pathological characteristics.
Fourth-line chemotherapy with pegylated liposomal doxorubicin and bevacizumab was
effective in treating the recurrent tumor, even though this disease had recurred
three times.
PMID- 28422376
TI - Spontaneous remission of hepatitis B virus reactivation during direct-acting
antiviral agent-based therapy for chronic hepatitis C.
AB - The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C
virus (HCV) infection has been reported to cause hepatitis B virus (HBV)
reactivation. However, the actual conditions of HBV reactivation and the ideal
timing of medical intervention have not been fully evaluated. We report the cases
of two female patients dually infected with HBV and HCV. Both patients were
inactive HBV carriers. Although the serum HCV RNA levels promptly decreased after
the initiation of DAA-based therapy, the serum HBV DNA levels gradually increased
during DAA-based therapy, with the peak serum HBV DNA levels observed at 16 weeks
after the initiation of DAA-based therapy in both cases. Subsequently, we checked
the serum HBV DNA levels closely every week several times. Fortunately, the serum
HBV DNA levels gradually decreased without medical intervention. Neither case
developed an alanine aminotransferase flare-up. The HCV genotypes were 2a and 1b,
and the DAA-based therapies of Cases 1 and 2 were 12 weeks of
sofosbuvir/ribavirin and ombitasvir/paritaprevir/ritonavir, respectively. The
significance of our case reports is the demonstration of the existence of
spontaneous remission of HBV reactivation that developed during DAA-based
therapy, the avoidance of intervention of nucleot(s)ide analogs by frequent
monitoring of serum HBV DNA levels, and development of HBV reactivation
regardless of the viral genotype or class of DAA. In conclusion, the close
monitoring of serum HBV DNA levels during and after DAA-based therapy is
essential and medical intervention for HBV reactivation should be carefully
considered on an individual basis.
PMID- 28422377
TI - Intraperitoneal gardiquimod protects against hepatotoxicity through inhibition of
oxidative stress and inflammation in mice with sepsis.
AB - Many reports recapitulate the contribution of reactive oxygen species (ROS) over
accumulation to the organ damage; it is of significance to strictly target ROS
production. In this study, we evaluated the potential role of TLR7 agonist
gardiquimod (GDQ) in oxidative stress (OS) in liver injury induced by sepsis.
Here, we observed that intraperitoneal pretreatment with GDQ dramatically
elevated the septic survival rate and effectively attenuated the septic liver
injury. Interestingly, the increased ROS and inflammatory factor IL-6 levels were
reversed after GDQ intervention. Subsequently, Western blot was employed to
determine the definite mechanism. As expected, it was showed that the
upregulation of c-Jun N-terminal kinase (JNK)/c-Jun pathway in liver of septic
animals was considerably suppressed by GDQ pre-exposure. Our current result
highlight that pre-administration of GDQ ameliorated sepsis induced
hepatotoxicity and reduced the generation of IL-6 and OS responses, which was
associated with downregulation of JNK/c-Jun pathway. Our strategies might be
ultimately beneficial in mitigating liver injury symptom.
PMID- 28422378
TI - Cellular retinoic acid bioavailability in various pathologies and its therapeutic
implication.
AB - Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling
molecule in various cell types. We found that RA depletion caused by expression
of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating
CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that
the biological effect of RA on target cells is primarily determined by "cellular
RA bioavailability", which is defined as the RA level in an individual cell,
rather than by the serum concentration of RA. Consistently, stellate cells store
approximately 80% of vitamin A in the body, and the state of cellular RA
bioavailability regulates their function. Based on the similarities between
stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate
tight junction-based endothelial integrity in a paracrine manner. Since diabetic
retinopathy is characterized by increased vascular permeability in its early
pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes,
resulting in suppression of vascular leakiness. RA also attenuated the loss of
the epithelial barrier in murine experimental colitis. The concept of "cellular
RA bioavailability" in various diseases will be directed at understanding various
pathologies caused by RA insufficiency, implying the potential feasibility of a
therapeutic strategy targeting the stellate cell system.
PMID- 28422379
TI - Increased 5-hydroxymethylation levels in the hippocampus of rat extinguished from
cocaine self-administration.
AB - Drug craving and relapse risk during abstinence from cocaine are thought to be
caused by persistent changes in transcription and chromatin regulation. Although
several brain regions are involved in these processes, the hippocampus seems to
play an important role in context-evoked craving and drug-seeking behavior. Only
a few studies have examined epigenetic alterations during a period of cocaine
abstinence. To investigate the effects of cocaine abstinence on DNA methylation
and gene expression, rats that self-administered the drug underwent cocaine
abstinence in two time points with extinction training. During the cocaine
extinction, we observed elevated global 5-hydroxymethylcytosine(5-hmC) levels
with a concurrent increase in Tet3 transcript levels. Moreover, we did not find
significant alterations in the levels of Tet3 mRNA and 5-hmC in rats subjected to
cocaine abstinence without extinction training. Additionally, our findings
demonstrated that the expression of Tet3 target genes was activated. Besides,
altered DNA methylation was detected at promoter regions of miRNAs, such as miR
30d and miR-let7i. Further in silico analysis provided evidence that these two
molecules targeted the 3' UTR region of the Tet3 gene and thus may contribute to
its post-transcriptional regulation. This study has presented novel findings in
the hippocampus of rats that underwent extinction training following cocaine self
administration. The alterations in the Tet3 gene expression and the level of 5
hmC may play an important role in extinction learning and the reduction of
subsequent cocaine seeking.
PMID- 28422380
TI - Comparing the long-acting and short-acting forms of gonadotropin-releasing
hormone agonists in the long protocol of IVF/ICSI Cycles: A retrospective study.
AB - AIM: This study aimed to compare the efficacy of long- and short-acting
gonadotropin-releasing hormone agonist on clinical outcomes of in vitro
fertilization/intracytoplasmic sperm injection (IVF/ICSI) long protocol cycles.
METHODS: In this retrospective study, 478 patients were enrolled from October
2012 to November 2014. The pituitary downregulation result, serum hormone levels,
gonadotropin (Gn) dose during controlled ovarian hyperstimulation, and outcome of
IVF/ICSI-embryo transfer were compared between the two groups. RESULTS: Compared
with the long-acting group, in the short-acting group the duration of
downregulation and stimulation was significantly shorter; the total Gn doses,
cost of an IVF cycle, rate of ovarian hyperstimulation syndrome, superior-quality
embryo rate, and implantation rate were significantly lower; and the serum
luteinizing hormone concentrations on the day of Gn and human chorionic
gonadotropin administration were significantly higher. The serum estradiol level
on the day of human chorionic gonadotropin was higher in the long-acting group.
However, no significant differences were noted in other parameters. CONCLUSION:
The long-acting group was associated with greater amounts of Gn and a longer
duration of use for ovarian stimulation. This increased the cost per IVF cycle
and may have had a detrimental effect on the pregnancy outcome because of a
subsequent increase in the rate of ovarian hyperstimulation syndrome and decrease
in the superior-quality embryo rate and implantation rate.
PMID- 28422381
TI - Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam
commissioning data.
AB - PURPOSE: Commissioning beam data for proton spot scanning beams are compared for
the first two Varian ProBeam sites in the United States, at the Maryland Proton
Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition,
the extent to which beams can be matched between gantry rooms at MPTC is
investigated. METHOD: Beam data for the two sites were acquired with independent
dosimetry systems and compared. Integrated depth dose curves (IDDs) were acquired
with Bragg peak ion chambers in a 3D water tank for pencil beams at both sites.
Spot profiles were acquired at different distances from the isocenter at a gantry
angle of 0 degrees as well as a function of gantry angles. Absolute dose
calibration was compared between SPTC and the gantries at MPTC. Dosimetric
verification of test plans, output as a function of gantry angle, monitor unit
(MU) linearity, end effects, dose rate dependence, and plan reproducibility were
compared for different gantries at MPTC. RESULTS: The IDDs for the two sites were
similar, except in the plateau region, where the SPTC data were on average 4.5%
higher for lower energies. This increase in the plateau region decreased as
energy increased, with no marked difference for energies higher than 180 MeV.
Range in water coincided for all energies within 0.5 mm. The sigmas of the spot
profiles in air were within 10% agreement at isocenter. This difference increased
as detector distance from the isocenter increased. Absolute doses for the
gantries measured at both sites were within 1% agreement. Test plans, output as
function of gantry angle, MU linearity, end effects, dose rate dependence, and
plan reproducibility were all within tolerances given by TG142. CONCLUSION: Beam
data for the two sites and between different gantry rooms were well matched.
PMID- 28422382
TI - Quantum dots-based fluorescence resonance energy transfer biosensor for
monitoring cell apoptosis.
AB - The development of advanced methods for accurately monitoring cell apoptosis has
extensive significance in the diagnostic and pharmaceutical fields. In this
study, we developed a rapid, sensitive and selective approach for the detection
of cell apoptosis by combining the site-specific recognition and cleavage of the
DEVD-peptide with quantum dots (QDs)-based fluorescence resonance energy transfer
(FRET). Firstly, biotin-peptide was conjugated on the surface of AuNPs to form
AuNPs-pep through the formation of an Au-S bond. Then, AuNPs-pep-QDs nanoprobe
was obtained through the connection between AuNPs-pep and QDs. FRET is on and the
fluorescence of QDs is quenched at this point. The evidence of UV-vis spectra,
transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR)
spectroscopy revealed that the connection was successful. Upon the addition of
apoptosis cell lysis solution, peptide was cleaved by caspase-3, and AuNPs was
dissociated from the QDs. At this time, FRET is off, and thus the QDs
fluorescence was recovered. The experimental conditions were optimized in terms
of ratio of peptide to AuNPs, buffer solution, and the temperature of conjugation
and enzyme reaction. The biosensor was successfully applied to distinguishing
apoptosis cells and normal cells within 2 h. This study demonstrated that the
biosensor could be utilized to evaluate anticancer drugs.
PMID- 28422383
TI - Liquid and subcritical fluid chromatographic enantioseparation of Nalpha -Fmoc
proteinogenic amino acids on Quinidine-based zwitterionic and anion-exchanger
type chiral stationary phases. A comparative study.
AB - Stereoselective high-performance liquid chromatographic and subcritical fluid
chromatographic separations of 19 Nalpha -Fmoc proteinogenic amino acid
enantiomers were carried out by using Quinidine-based zwitterionic and anion
exchanger-type chiral stationary phases Chiralpak ZWIX(-) and QD-AX. For
optimization of retention and enantioselectivity, the ratio of bulk solvent
components (MeOH/MeCN, H2 O/MeOH, or CO2 /MeOH) and the nature and concentration
of the acid and base additives (counter- and co-ions) were systematically varied.
The effect of column temperature on the enantioseparation was investigated and
thermodynamic parameters were calculated from the van't Hoff plots ln alpha vs.
1/T. The thermodynamic parameters revealed that the enantioseparations were
enthalpy-driven. The elution sequence was determined in all cases and with the
exception of Fmoc-Cys(Trt)-OH, it was identical on both chiral stationary phases
whereby the L-enantiomers eluted before the D-enantiomers.
PMID- 28422384
TI - Natural antioxidant flavonoids in formalin-induced mice paw inflammation;
inhibition of mitochondrial sorbitol dehydrogenase activity.
AB - Flavonoids have reported to cover interesting multiple pharmacological
properties. This study evaluated the effect of apigenin or silymarin in paw
inflammation induced by formalin in mice. Mice were divided into four groups: I:
positive control group; II: apigenin, 3 mg/kg (i.p.); III: silymarin 50 mg/kg
(p.o.); IV: meloxicam 10 mg/kg (p.o.), the reference drug. Therapies were
administered once a day for 7 days. The curative effects were assessed on
inflammatory, oxidative stress and neurotransmitter biomarkers, and apoptosis.
Both flavonoids induced marked improvement in paw licking time, paw edema %,
malondialdehyde content, superoxide dismutase, and sorbitol dehydrogenase
activities, with slight progress in paw interlukin-1beta. Additionally, silymarin
augmented brain content of dopamine and norepinephrine. Furthermore, flavonoids
induced marked decline in extent of apoptosis. So, the results spotlight on the
good influence of apigenin or silymarin as anti-inflammatory, antioxidant, and
antiapoptotic agents in formalin-induced mice paw inflammation to even a better
extent than meloxicam.
PMID- 28422385
TI - Genital bleeding hemostasis in gynecologic neoplasm with balloon tamponade: New
treatment option.
AB - Genital bleeding is the most common and serious complication in gynecologic
malignancy. Different techniques are available for the control of severe
bleeding, but standard treatment strategies have not been determined. Herein we
report on the successful use of the balloon technique in two cases of genital
bleeding in uterine neoplasm. The first case was of advanced cervical cancer with
massive genital bleeding during radiotherapy. A metreurynter (mini-metro) was
inserted into the vagina and hemostasis was indirectly achieved in the vaginal
hematoma. The other case was of postoperative recurrent bleeding after cervical
conization. A Foley balloon catheter was inserted into the endocervical canal and
balloon tamponade directly stopped the bleeding. This technique is safe for
massive genital bleeding in some cases of gynecological cancer, and can be
conventionally performed regardless of the facility or department. The need for
invasive treatment for fatal bleeding in gynecological cancer in which gauze
packing is ineffective may be avoided by balloon tamponade without serious
complications.
PMID- 28422386
TI - Corticosteroid might reduce serum levels of pro-inflammatory cytokines in
fulminant hepatitis: A case series.
AB - AIM: There are no beneficial therapies except for emergency liver transplantation
for acute liver failure (ALF). However, in Japan, which has a serious problem in
the shortage of donor livers, therapies other than transplantation must be
further investigated for patients with ALF. Pro-inflammatory cytokines promoting
tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS)
influences monocyte/macrophage differentiation, by suppressing pro-inflammatory
genes, indicating CS treatment might be beneficial during the early phase of ALF.
Our aim was to elucidate the efficacy of CS pulse therapy in decreasing pro
inflammatory cytokine levels in the early stage of ALF. METHODS: Ten consecutive
adult Japanese patients with fulminant hepatitis in the early stage, three
treated with artificial liver support (ALS) and CS pulse therapy (ALS + CS group)
and seven treated with ALS (ALS group), were enrolled. Clinical and biochemical
data on admission were matched between the groups and retrospectively analyzed
for serum concentrations of interleukin-6, tumor necrosis factor-alpha, and
interleukin-1beta over a 2-week period. RESULTS: Mean cytokine levels on
admission were not different between the two groups. Tumor necrosis factor-alpha
was significantly reduced on day 7 in patients with CS. Serum levels of pro
inflammatory cytokines tended to be reduced in patients with CS compared to those
without during the observation period, although the differences were not
significant. CONCLUSIONS: It might be possible that introduction of CS pulse
therapy in the early stage of ALF could reduce levels of pro-inflammatory
cytokines, which might inhibit the cascade of progression of ALF.
PMID- 28422387
TI - Should we be putting our scalpels down? Is HIFU the answer to fertility-sparing
fibroid treatment?
PMID- 28422388
TI - Comparison of the effectiveness of two different interventions to reduce
preoperative anxiety: A randomized controlled study.
AB - This study was conducted to determine and compare the effectiveness of nature
sounds and relaxation exercises for reducing preoperative anxiety. A repeated
measures randomized controlled trial design was used. We divided 159 preoperative
patients into three groups: nature sounds (n = 53), relaxation exercises (n =
53), and control groups (n = 53). We evaluated anxiety using the visual analog
scale and state anxiety inventory scores immediately before, immediately after,
and 30 min after interventions in nature sounds and relaxation exercises groups,
and silent rest in the control. We found no differences between the measurement
values in the intervention groups, but we did observe a difference between the
intervention and control groups. The two interventions were similarly effective
in reducing preoperative anxiety. These simple and low-cost interventions can be
used to reduce preoperative anxiety in surgical clinics.
PMID- 28422389
TI - Triosephosphate isomerase tyrosine nitration induced by heme-NaNO2 -H2 O2 or
peroxynitrite: Effects of different natural phenolic compounds.
AB - Peroxynitrite and heme peroxidases (or heme)-H2 O2 -NaNO2 system are the two
common ways to cause protein tyrosine nitration in vitro, but the effects of
antioxidants on reducing these two pathways-induced protein nitration and
oxidation are controversial. Both nitrating systems can dose-dependently induce
triosephosphate isomerase (TIM) nitration, however, heme-H2 O2 -NaNO2 was less
destructive to protein secondary structures and led to more nitrated tyrosine
residue than 3-morpholinosydnonimine hydrochloride (SIN-1, a peroxynitrite
donor). Both of desferrioxamine and catechin could inhibit TIM nitration induced
by heme-H2 O2 -NaNO2 and SIN-1 and protein oxidation induced by SIN-1, but
promoted heme-H2 O2 -NaNO2 -induced protein oxidation. Moreover, the antagonism
of natural phenolic compounds on SIN-1-induced tyrosine nitration was consistent
with their radical scavenging ability, but no similar consensus was found in heme
H2 O2 -NaNO2 -induced nitration. Our results indicated that peroxynitrite and
heme-H2 O2 -NaNO2 -induced protein nitration was different, and the later one
could be a better model for anti-nitration compounds screening.
PMID- 28422390
TI - Naringin abates adverse effects of cadmium-mediated hepatotoxicity: An
experimental study using HepG2 cells.
AB - This study investigated the protective potential of Naringin (NIN) against
cadmium chloride (CdCl2 ) mediated hepatotoxicity using human hepatocellular
carcinoma (HepG2) cells. An optimal concentration of NIN (5 MUM) was potent
enough to confer cytoprotection against CdCl2 (50 MUM) as was observed by MTT
assay. Preconditioning with NIN maintained redox homeostasis, mitochondrial
membrane potential, and reduced apoptosis as marked by decrease in the percentage
sub-G0 /G1 and Annexin V-FITC/propidium iodide positive cells (apoptotic). NIN
pretreatment maintained the levels of protein thiol along with endogenous
activities of Superoxide dismutase, Glutathione S-transferase, and Catalase and
lowered lipid peroxidation. Decreased Bax/Bcl2 ratio along with reduced Caspase 3
cleavage and Cytochrome c release indicated that NIN conditioning blocked
mitochondrial-mediated apoptosis. Increased Nrf2 and metallothionein (MT) acted
as adaptive response in the presence of cadmium. Thus, the protective mechanism
of NIN is attributed to its antioxidant potential which aids in redox homeostasis
and prevents CdCl2 mediated cytotoxicity.
PMID- 28422391
TI - MR elastography detection of early viscoelastic response of the murine
hippocampus to amyloid beta accumulation and neuronal cell loss due to
Alzheimer's disease.
AB - PURPOSE: To investigate in vivo viscoelastic parameters related to early
histopathological changes in the hippocampus and the cortex in early, preclinical
Alzheimer's disease (AD) stages. MATERIALS AND METHODS: Magnetic resonance
elastography (MRE) was applied to female APP23 mice, an established transgenic
mouse model of AD, at three different stages early in disease progression. To
investigate the potential therapeutic effects of physical, cognitive, and social
stimulation on brain viscoelasticity and histopathological characteristics, MRE
was also applied after exposing young APP23 mice to environmentally enriched cage
conditions (ENR), for 1, 12, or 24 weeks, which corresponds to adolescent, young
adult, and adult age at the time of analysis. RESULTS: Viscosity in the
hippocampus of APP23 mice is lower than in controls (CTR) (P = 0.005) and does
not increase with age, as in CTR mice (adolescent vs. young-adult: P = 1.000, vs.
adult: P = 0.493, young-adult vs. adult: P = 1.000). Hippocampal cell numbers
decrease with disease progression in APP23 mice (P < 0.001). Elasticity in the
hippocampus is also reduced in APP23 mice (P = 0.024) but increases (P = 0.027)
with disease progression. ENR in APP23 mice transiently increased hippocampal
cell numbers (P = 0.002) but not viscosity (P = 0.838). CONCLUSION: MRE detects
alterations in viscoelasticity in the hippocampus related to early
histopathological changes in the APP23 mouse model of AD. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:105-114.
PMID- 28422392
TI - Hepatic artery reconstruction in living donor liver transplantation using
surgical loupes: Achieving low rate of hepatic arterial thrombosis in 741
consecutive recipients-tips and tricks to overcome the poor hepatic arterial
flow.
AB - The reconstruction of the hepatic artery (HA) is the most complex step in living
donor liver transplantation (LDLT) because of the smaller diameter of the artery
and the increased risk of HA-related complications. Because of the smaller
diameter of the HA, many centers use a microsurgical technique with interrupted
sutures for arterial anastomosis. The aim of our study was to retrospectively
investigate the outcomes after HA reconstruction performed under magnifying
loupes using the "parachute technique." From August 1, 2002 to August 31, 2016,
LDLT was performed in 766 recipients. HA reconstruction for the initial 25 LDLT
surgeries was performed using a microsurgery technique (era 1). From May 2007
until the end date, HA reconstruction was performed in 741 recipients by a
"parachute technique" under surgical loupes (era 2). HA reconstruction was
performed using surgical loupes in 737 adults (male:female, 526:211) and 4
pediatric patients (male:female, 3:1). The average diameter of the donor graft HA
was 2.8 mm (range, 1-6.5 mm). The most notable factor in this era was the quick
HA anastomosis procedure with a mean time of 10 +/- 5 minutes (range, 5-30
minutes). In era 2, 9 (1.21%) patients developed hepatic artery thrombosis (HAT),
whereas 2 patients developed nonthrombotic HA-related complications. Extra
anatomic HA reconstruction was performed in 14 patients due to either primary HA
anastomosis failure or a poor caliber recipient HA. The use of magnifying
surgical loupes to perform HA reconstruction is safe, feasible, and yields a low
incidence of HA-related complications. The "parachute technique" for HA
reconstruction can achieve a speedy reconstruction without increasing the risk of
HAT. Liver Transplantation 23 887-898 2017 AASLD.
PMID- 28422393
TI - Accuracy and response time of dual biomarker model of insulin-like growth factor
binding protein-1/ alpha fetoprotein (Amnioquick duo+) in comparison to placental
alpha-microglobulin-1 test in diagnosis of premature rupture of membranes.
AB - AIM: The aim of this study was to determine accuracy and response time of duo of
insulin-like growth factor binding protein-1 (IGFBP-1)/alpha-fetoprotein
(Amnioquick duo+) versus placental alpha-microglobulin-1 (PAMG-1) in diagnosing
premature rupture of membranes (PROM). METHODS: A multicenter prospective study
was conducted among women with features suggestive of PROM between 24 and 42
gestational weeks (GW). PROM was confirmed post-delivery based on presence of any
two of these criteria: delivery within 48 h to 7 days, chorioamnionitis,
membranes overtly ruptured at delivery, and adverse perinatal outcomes strongly
correlated with prolonged PROM. Response time analysis was also done. Outcome
measures included specificity, sensitivity, positive predictive value, negative
predictive value, accuracy, and response time for both tests. RESULTS:
Sensitivity, specificity, and accuracy for Amnioquick duo+ were 97.9%, 97.6%, and
97.9%, which were higher than the levels for PAMG-1, of 95.3%, 90.0%, and 95.7%,
respectively (not significant). Accuracy of Amnioquick duo+ versus PAMG-1 in
equivocal (pooling = negative) cases was (98.4% vs 96.8%) at >=34 GW but each was
100.0% at <34 GW (not significant). Overall diagnostic concordance rate of
Amnioquick duo+ and PAMG-1 was 97.0% and both have equal positive predictive
value (99.5%). Response time analysis showed that the overall response time of
PAMG-1 was 4.5% higher than that of Amnioquick duo+. CONCLUSION: This is the
largest study to date to reveal that Amnioquick duo+ and PAMG-1 have a
comparatively high diagnostic accuracy in identifying women with PROM, with a
concordance rate of 97.0%. The diagnostic response time of Amnioquick duo+
appears shorter. In equivocal cases, accuracy of Amnioquick duo+ was equal to
that of the PAMG-1.
PMID- 28422394
TI - Homozygous variant in C21orf2 in a case of Jeune syndrome with severe thoracic
involvement: Extending the phenotypic spectrum.
AB - We previously reported exome sequencing in a short-rib thoracic dystrophy (SRTD)
cohort, in whom recessive mutations were identified in SRTD-associated genes in
10 of 11 cases. A heterozygous stop mutation in the known SRTD gene WDR60 was
identified in the remaining case; no novel candidate gene/s were suggested by
homozygous/compound heterozygous analysis. This case was thus considered
unsolved. Re-analysis following an analysis pipeline update identified a
homozygous mutation in C21orf2 (c.218G > C; p.Arg73Pro). This homozygous variant
was previously removed at the quality control stage by the default GATK parameter
"in-breeding co-efficient." C21orf2 was recently associated with both Jeune
asphyxiating thoracic dystrophy (JATD) and axial spondylometaphyseal dysplasia
(axial SMD); this particular mutation was reported in homozygous and compound
heterozygous state in both conditions. Our case has phenotypic features of both
JATD and axial SMD; and the extent of thoracic involvement appears more severe
than in other C21orf2-positive cases. Identification of a homozygous C21orf2
mutation in this case emphasizes the value of exome sequencing for simultaneously
screening known genes and identifying novel genes. Additionally, it highlights
the importance of re-interrogating data both as novel gene associations are
identified and as analysis pipelines are refined. Finally, the severity of
thoracic restriction in this case adds to the phenotypic spectrum attributable to
C21orf2 mutations.
PMID- 28422395
TI - Chiral determination of cinchonine using an electrochemiluminescent sensor with
molecularly imprinted membrane on the surfaces of magnetic particles.
AB - A novel molecular imprinting electrochemiluminescence sensor for detecting chiral
cinchonine molecules was developed with a molecularly imprinted polymer membrane
on the surfaces of magnetic microspheres. Fe3 O4 @Au nanoparticles modified with
6-mercapto-beta-cyclodextrin were used as a carrier, cinchonine as a template
molecule, methacrylic acid as a functional monomer and N,N'
methylenebisacrylamide as a cross-linking agent. Cinchonine was specifically
recognized by the 6-mercapto-beta-cyclodextrin functional molecularly imprinted
polymer and detected based on enhancement of the electrochemiluminescence
intensity caused by the reaction of tertiary amino structures of cinchonine
molecules with Ru(bpy)32+ . Cinchonine concentrations of 1 * 10-10 to 4 * 10-7
mol/L showed a good linear relationship with changes of the
electrochemiluminescence intensity, and the detection limit of the sensor was
3.13 * 10-11 mol/L. The sensor has high sensitivity and selectivity, and is easy
to renew. It was designed for detecting serum samples, with recovery rates of
98.2% to 107.6%.
PMID- 28422396
TI - A simplified multivisceral transplantation procedure for patients with combined
end-stage liver disease and type 2 diabetes mellitus.
AB - In liver transplant patients with type 2 diabetes mellitus (DM), the disease
worsens after transplantation because of longterm use of diabetogenic
immunosuppressive drugs, making management of those patients a great challenge.
The objective of our study was to evaluate the safety and efficacy of a
simplified multivisceral transplantation (SMT) procedure for the treatment of
patients with end-stage liver disease and concurrent type 2 DM. Forty-four
patients who had pretransplant type 2 DM were included. A total of 23 patients
received SMT, and 21 patients received orthotopic liver transplantation (OLT).
Patient and graft survivals, complications, diabetic control, and quality of life
(QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year
cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the
SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P =
0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from
DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of
biliary complication was significantly higher in the OLT group than that in the
SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the
SMT group than that in the OLT group. In conclusion, the SMT procedure we
described here is a safe and viable option for patients with end-stage live
disease and concurrent type 2 DM. This SMT procedure offers excellent transplant
outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.
PMID- 28422397
TI - A novel radiation protection device based on tungsten functional paper for
application in interventional radiology.
AB - Tungsten functional paper (TFP), which contains 80% tungsten by weight, has
radiation-shielding properties. We investigated the use of TFP for the protection
of operators during interventional or therapeutic angiography. The air kerma rate
of scattered radiation from a simulated patient was measured, with and without
TFP, using a water-equivalent phantom and fixed C-arm fluoroscopy. Measurements
were taken at the level of the operator's eye, chest, waist, and knee, with a
variable number of TFP sheets used for shielding. A Monte Carlo simulation was
also utilized to analyze the dose rate delivered with and without the TFP
shielding. In cine mode, when the number of TFP sheets was varied through 1, 2,
3, 5, and 10, the respective reduction in the air kerma rate relative to no TFP
shielding was as follows: at eye level, 24.9%, 29.9%, 41.6%, 50.4%, and 56.2%; at
chest level, 25.3%, 33.1%, 34.9%, 46.1%, and 44.3%; at waist level, 45.1%, 57.0%,
64.4%, 70.7%, and 75.2%; and at knee level, 2.1%, 2.2%, 2.1%, 2.1%, and 2.1%. In
fluoroscopy mode, the respective reduction in the air kerma rate relative to no
TFP shielding was as follows: at eye level, 24.8%, 30.3%, 34.8%, 51.1%, and
58.5%; at chest level, 25.8%, 33.4%, 35.5%, 45.2%, and 44.4%; at waist level,
44.6%, 56.8%, 64.7%, 71.7%, and 77.2%; and at knee level, 2.2%, 0.0%, 2.2%, 2.8%,
and 2.5%. The TFP paper exhibited good radiation-shielding properties against the
scattered radiation encountered in clinical settings, and was shown to have
potential application in decreasing the radiation exposure to the operator during
interventional radiology.
PMID- 28422398
TI - Do mHealth interventions prevent excessive gestational weight gain?
PMID- 28422399
TI - Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome (CRPS)
Recurrence after Amputation for CRPS, and Failure of Conventional Spinal Cord
Stimulation.
AB - BACKGROUND: Limb amputation is sometimes being performed in long-standing complex
regional pain syndrome (CRPS), although little evidence is available guiding
management decisions, including how CRPS recurrence should be managed. METHODS:
This report details the management of a young soldier with CRPS recurrence 2
years after midtibial amputation for CRPS. RESULTS: Conventional spinal cord
stimulation did not achieve paraesthetic coverage, or pain relief in the stump,
whereas L4 dorsal root ganglion stimulation achieved both coverage and initially
modest pain relief, and over time, substantial pain relief. CONCLUSIONS: Current
evidence does not support the use of amputation to improve either pain or
function in CRPS. Before a decision is made, in exceptional cases, about referral
for amputation, dorsal root ganglion stimulation should be considered as a
potentially effective treatment, even where conventional spinal cord stimulator
treatment has failed to achieve reliable paraesthetic cover. Furthermore, this
treatment may provide pain relief in those patients with CRPS recurrence in the
stump after amputation.
PMID- 28422401
TI - MLC-based penumbra softener of EDW borders to reduce junction inhomogeneities.
AB - Junctions of fields are known to be susceptible to developing cold or hot spots
in the presence of even small geometrical misalignments. Reduction of these dose
inhomogeneities can be accomplished through decreasing the dose gradients in the
penumbra, but currently it cannot be done for enhanced dynamic wedges (EDW). An
MLC-based penumbra softener was developed in the developer mode of TrueBeam
linacs to reduce dose gradients across the side border of EDWs. The movement of
each leaf was individually synchronized with the movement of the dynamic Y jaw to
soften the penumbra in the same manner along the entire field border, in spite of
the presence of the dose gradient of the EDW. Junction homogeneity upon field
misalignment for side-matched EDWs was examined with the MV imager. The fluence
inhomogeneities were reduced from about 30% per mm of shift of the field borders
for the conventional EDW to about 2% per mm for the softened-penumbra plan. The
junction in a four-field monoisocentric breast plan delivered to the Rando
phantom was assessed with film. The dose inhomogeneities across the junction in
the superior-inferior direction were reduced from about 20% to 25% per mm for the
conventional fields to about 5% per mm. The dose near the softened junction of
the breast plan with no shifts did not deviate from the conventional plan by more
than about 4%. The newly-developed softened-penumbra junction of EDW (and/or
open) fields was shown to reduce sensitivity to misalignments without increasing
complexity of the planning or delivery. This methodology needs to be adopted by
the manufacturers for clinical use.
PMID- 28422402
TI - Gypenoside inhibits interleukin-1beta-induced inflammatory response in human
osteoarthritis chondrocytes.
AB - Gypenoside (GP), the main active ingredient of Gynostemma pentaphyllum, possesses
a variety of pharmacological capacities including anti-inflammation, anti
oxidation, and anti-tumor. However, the effects of GP on IL-1beta-stimulated
human osteoarthritis (OA) chondrocytes are still unknown. Therefore, this study
aimed to investigate the anti-inflammatory effects of GP on IL-1beta-stimulated
human OA chondrocytes and explore the possible mechanism. Our results showed that
GP dose-dependently inhibited IL-1beta-induced NO and PGE2 production in human OA
chondrocytes. In addition, treatment of GP inhibited the expression of MMP3 and
MMP13, which was increased by IL-1beta. Finally, we found that pretreatment of GP
obviously suppressed NF-kappaB activation in IL-1beta-stimulated human OA
chondrocytes. Taken together, the results demonstrated that GP has chondro
protective effects, at least in part, through inhibiting the activation of NF
kappaB signaling pathway in human OA chondrocytes. Thus, these findings suggest
that GP may be considered as an alternative therapeutic agent for the management
of OA patients.
PMID- 28422400
TI - Sequence-Specific Covalent Capture Coupled with High-Contrast Nanopore Detection
of a Disease-Derived Nucleic Acid Sequence.
AB - Hybridization-based methods for the detection of nucleic acid sequences are
important in research and medicine. Short probes provide sequence specificity,
but do not always provide a durable signal. Sequence-specific covalent crosslink
formation can anchor probes to target DNA and might also provide an additional
layer of target selectivity. Here, we developed a new crosslinking reaction for
the covalent capture of specific nucleic acid sequences. This process involved
reaction of an abasic (Ap) site in a probe strand with an adenine residue in the
target strand and was used for the detection of a disease-relevant T->A mutation
at position 1799 of the human BRAF kinase gene sequence. Ap-containing probes
were easily prepared and displayed excellent specificity for the mutant sequence
under isothermal assay conditions. It was further shown that nanopore technology
provides a high contrast-in essence, digital-signal that enables sensitive,
single-molecule sensing of the cross-linked duplexes.
PMID- 28422404
TI - Use of resuscitation plans at a tertiary Australian hospital: room for
improvement.
AB - BACKGROUND: The 'Acute Resuscitation Plan' (ARP) is a document for recording the
resuscitation plans of patients at a tertiary hospital for adult patients. The
ARP was introduced at the hospital in September 2014, superseding the 'Not for
Cardiopulmonary Resuscitation (CPR)' form. Unlike the Not for CPR form, the ARP
was relevant to patients with and without resuscitation limits. AIM: To evaluate
the introduction of the ARP. METHODS: This study is a retrospective audit of the
records of all admissions to the hospital from January to June 2014 (Not for CPR
period) and January to June 2015 (ARP period). The main outcomes are the
incidence of resuscitation plans, the proportion of ARP specifying consultation
with the patient (or representative) and with senior medical staff, and the
proportion of ARP among older patients and those with significant comorbidity.
RESULTS: Resuscitation plans were present for 453 of 23 325 (1.9%) admissions in
the Not for CPR period versus 1801 of 24 037 (7.5%) in the ARP period (odds ratio
(OR) 4.1, 95% confidence interval (CI) 3.7-4.5, P < 0.001). A total of 42% of ARP
specified 'care of the dying' in the event of arrest. Acknowledgement of the
views of the patient (or representative) was indicated on 37% of ARP and of a
senior physician on 28%. An ARP was not present for 67% of patients aged >=90
years, 59% from aged care, 90% with metastatic cancer and 64% aged >=80 years and
with a Charlson comorbidity index >=3. CONCLUSIONS: More patients had
resuscitation plans after introducing the ARP. However, patients and senior
physicians were often remote from the consultation process, and an ARP was not
present for many patients likely to have a poor outcome from cardiopulmonary
arrest.
PMID- 28422403
TI - Blood Chimerism in Dizygotic Monochorionic Twins During 5 Years Observation.
AB - Dizygotic monochorionic twin pregnancies can result in blood chimerism due to in
utero twin-to-twin exchange of stem cells. In this case, we examined the
proportion of allogeneic red blood cells by flow cytometry and the proportion of
allogeneic nucleated cells by digital polymerase chain reaction at 7 months and
again at 5 years. We found an increase in the proportion of allogeneic cells from
63% to 89% in one twin, and a similar increase in autologous cells in the other
twin from 57% to 84%. A paradigm for stem cell therapy could be modeled on this
case: induction of tolerance and chimerism by antenatal transfusion of donor stem
cells. The procedure would hold the promise of transplantation and tolerance
induction without myeloablative conditioning for inheritable benign hematological
diseases such as sickle cell disease and thalassemia.
PMID- 28422406
TI - Comparability of three output prediction models for a compact passively double
scattered proton therapy system.
AB - The purpose of this study was to investigate comparability of three output
prediction models for a compact double-scattered proton therapy system. Two
published output prediction models are commissioned for our Mevion S250 proton
therapy system. Model A is a correction-based model (Sahoo et al., Med Phys,
2008;35(11):5088-5097) and model B is an analytical model which employs a
function of r = (R'-M')/M' (Kooy et al., Phys Med Biol, 2005;50:5487-5456) where
R' is defined as depth of distal 100% dose with straggling and M' is the width
between distal 100% dose and proximal 100% dose with straggling instead of the
theoretical definition due to more accurate output prediction. The r is converted
to ((R-0.31)-0.81 * M)/(0.81 * M) with the vendor definition of R (distal 90%
dose) and M (distal 90% dose-to-proximal 95% dose), where R' = R-0.31 (g cm-2 )
and M' = 0.81 * M (g cm-2 ). In addition, a quartic polynomial fit model (model
C) mathematically converted from model B is studied. The outputs of 272 sets of R
and M covering the 24 double scattering options are measured. Each model's
predicted output is compared to the measured output. For the total dataset, the
percent difference between predicted (P) and measured (M) outputs ((P-M)/M *
100%) were within +/-3% using the three different models. The average differences
(+/-standard deviation) were -0.13 +/- 0.94%, -0.13 +/- 1.20%, and -0.22 +/-
1.11% for models A, B, and C, respectively. The p-values of the t-test were 0.912
(model A vs. B), 0.061 (model A vs. C), and 0.136 (model B vs. C). For all the
options, all three models have clinically acceptable predictions. The differences
between models A, B, and C are statistically insignificant; however, model A
generally has the potential to more accurately predict the output if a larger
dataset for commissioning is used. It is concluded that the models can be
comparably used for the compact proton therapy system.
PMID- 28422407
TI - Mutations in TGDS associated with additional malformations of the middle fingers
and halluces: Atypical Catel-Manzke syndrome in a fetus.
AB - Pierre-Robin sequence, radial deviation, and ulnar clinodactyly of the index
fingers due to an additional phalangeal bone, as well as heart defects are the
key features of Catel-Manzke syndrome. Although mutations in TGDS were identified
as the cause of this disorder, the pathogenetic mechanism remains unknown. Here,
we report on a fetus with severe heart defect, nuchal edema, talipes, Pierre
Robin sequence, and bilateral deviation and clinodactyly of the index and middle
fingers. Pregnancy was terminated at the 22nd week of gestation. Postmortem
radiographs showed hypoplasia and V-shaped displacement of the second and third
proximal phalanges of both hands as well as hypoplasia of the first metatarsals
and the phalangeal bones of the halluces. The suggested diagnosis Catel-Manzke
syndrome was confirmed by the detection of two compound heterozygous mutations in
TGDS: The known variant c.298G>T; p.(Ala100Ser) and the so far undescribed
variant c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site
of TGDS. This is the first report on the association of mutations in TGDS with
additional anomalies of the middle fingers and halluces. We provide a detailed
phenotypic characterization of the only fetus with molecularly confirmed Catel
Manzke syndrome, which is relevant for prenatal diagnosis. Our findings widen the
phenotype spectrum caused by TGDS mutations and underline the phenotypic overlap
with Temtamy preaxial brachydactyly syndrome. This improves our understanding of
the prenatal development and the pathogenetic mechanism of Catel-Manzke syndrome.
PMID- 28422408
TI - Prevention of the Osmotic Demyelination Syndrome After Liver Transplantation: A
Multidisciplinary Perspective.
AB - The osmotic demyelination syndrome (ODS) is a serious neurologic condition that
occurs in the setting of rapid correction of hyponatremia. It presents with
protean manifestations, from encephalopathy to the "locked-in" syndrome. ODS can
complicate liver transplantation (LT), and its incidence may increase with the
inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score.
A comprehensive understanding of risk factors for the development of ODS in the
setting of LT, along with recommendations to mitigate the risk of ODS, are
necessary. The literature to date on ODS in the setting of LT was reviewed. Major
risk factors for the development of ODS include severe pretransplant hyponatremia
(serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus
posttransplant, higher positive intraoperative fluid balance, and the presence of
postoperative hemorrhagic complications. Strategies to reduce the risk of ODS
include correcting hyponatremia pretransplant via fluid restriction and/or
ensuring an appropriate rate of increase from the preoperative SNa via close
attention to fluid and electrolyte management both during and after surgery.
Multidisciplinary management involving transplant hepatology, nephrology,
neurology, surgery, and anesthesiology/critical care is key to performing LT
safely in patients with hyponatremia.
PMID- 28422409
TI - Validation of the Japanese Version of the Fremantle Back Awareness Questionnaire
in Patients with Low Back Pain.
AB - BACKGROUND: There is a growing interest in the role of disturbed body perception
in people with persistent pain problems such as chronic low back pain (CLBP). A
questionnaire, the Fremantle Back Awareness Questionnaire (FreBAQ), was recently
developed as a simple and quick way of assessing disturbed perceptual awareness
of the back in people with CLBP and appears to have acceptable psychometric
properties. The aim of the present study was to develop a Japanese version of the
FreBAQ (FreBAQ-J) and evaluate its psychometric properties in a sample of
Japanese people with low back pain (LBP). METHODS: Translation of the FreBAQ into
Japanese was conducted using a forward-backward method. One hundred participants
with LBP completed the resultant FreBAQ-J. A subset of the participants completed
the FreBAQ-J again 2 weeks later. Validity was investigated by examining the
relationship between the FreBAQ-J and clinical valuables. Rasch analysis was used
to assess targeting, category ordering, unidimensionality, person fit, internal
consistency, and differential item functioning. RESULTS: The FreBAQ-J was
significantly correlated with pain in motion, disability, pain-related
catastrophizing, fear of movement, and anxiety symptomatology. The FreBAQ-J had
acceptable internal consistency, a minor departure from unidimensionality, and
good test-retest reliability, and was functional on the category rating scale.
CONCLUSIONS: The FreBAQ-J has acceptable psychometric properties and is suitable
for use in people with LBP. Participants with high levels of disturbed body
perception are well targeted by the scale. The functioning of one item (item 8)
was poor. Further study is warranted to confirm if this item should be excluded.
PMID- 28422410
TI - Reply to Comment on the Article "OPTN/SRTR 2015 Annual Data Report: Pancreas".
PMID- 28422411
TI - Optical properties of Eu2+ /Eu3+ mixed valence phosphor Ca2 SiO2 F2 :Eu2+ /Eu3.
AB - The Eu2+ /Eu3+ mixed valence phosphor Ca2 SiO2 F2 :Eu2+ /Eu3+ was prepared using
a solid-state reaction synthesis method in a CO atmosphere, and the optical
properties were investigated. The spectroscopic properties revealed that Ca2+
ions were occupied by both Eu2+ and Eu3+ ions in Ca2 SiO2 F2 , and both ions were
able to generate their characteristic emissions. A broad 5d -> 4f Eu2+ band at
~470 nm and narrow 4f -> 4f Eu3+ peaks upon excitation with n-UV light were
observed. The ratio between Eu2+ and Eu3+ emissions changed regularly, and the
relative intensity of the red component from Eu3+ became systematically stronger
with increasing overall Eu content. As a result, the emission color of these
phosphors can be tunable from blue to pink under n-UV light excitation.
PMID- 28422412
TI - Histological Evolution of BK Virus-Associated Nephropathy: Importance of
Integrating Clinical and Pathological Findings.
AB - Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are
not available. We studied 206 biopsies (71 patients), followed 3.09 +/- 1.46
years after immunosuppression reduction. The biopsy features (% immunostain for
PyV large T ag + staining and inflammation +/- acute rejection) were correlated
with viral load dynamics and serum creatinine to define the clinicopathological
status (PyVCPS). Incidence of acute rejection was 28% in the second biopsy and
50% subsequently (25% mixed T cell-mediated allograft rejection (TCMR) + antibody
mediated allograft rejection (AMR); rejection overall affected 38% of patients
(>50% AMR). Graft loss was 15.4% (0.8-5.3 years after PyVAN); 76% had complete
viral clearance (mean 28 weeks). The only predictors of graft loss were acute
rejection (TCMR p = 0.008, any type p = 0.07), and increased "t" and "ci" in the
second biopsy (p = 0.006 and 0.048). Higher peak viremia correlated with poorer
viral clearance (p = 0.002). Presumptive and proven PyVAN had similar
presentation, evolution, and outcome. Late PyVAN (>2 years, 9.8%) justifies BK
viremia evaluation at any point with graft dysfunction and/or biopsy evaluation.
This study describes the histological evolution of PyVAN and corresponding
clinicopathological correlations. Although the pathological features overall
reflect the viral and immunological interactions, the PyVAN course remains
difficult to predict based on any single feature. Appropriate clinical management
requires repeat biopsies and determination of the PyVCPS at relevant time points,
for corresponding personalized immunosuppression adjustment.
PMID- 28422413
TI - Essential Oils as Biocides for the Control of Fungal Infections and Devastating
Pest (Tuta absoluta) of Tomato (Lycopersicon esculentum Mill.).
AB - Thymus capitatus and Tetraclinis articulata essential oils as well their major
components (carvacrol and alpha-pinene) were evaluated for their antifungal and
insecticidal activities. Both oils showed good in vitro antifungal activity
against Fusarium oxysporum, Aspergillus niger, Penicillium sp., Alternaria
alternata, and Botrytis cinerea, the fungi causing tomato rot. In vivo results
indicate the efficacies of both essential oils and carvacrol of reduce
postharvest fungal pathogens, such as B. cinerea and Al. alternata that are
responsible of black and gray rot of tomato fruit. Disease incidence of Al.
alternata and B. cinerea decreased on average from 55% to 80% with essential oil
of Th. capitatus and pure carcvacrol, while Te. articulata essential oil
exhibited inhibition of fungal growth of 55% and 25% against Al. alternata and B.
cinerea, respectively, with concentration of 0.4 MUl/l air. The insecticidal
activity of Th. capitatus and Te. articulata essential oils exhibited also a good
insecticidal activity. At the concentration of 0.2 MUl/ml air, the oils caused
mortality over 80% for all larval stages of Tuta absoluta and 100% mortality for
the first-instar after 1.5 h only of exposure. alpha-Pinene presented lower
insecticidal and antifungal activities compared to essential oils of Th.
capitatus, Te. articulata and pure carvacrol. Thus, these essential oils can be
used as a potential source to develop control agents to manage some of the main
pests and fungal diseases of tomato crops.
PMID- 28422415
TI - Impact of hospitalization in an acute geriatric unit on polypharmacy and
potentially inappropriate prescriptions: A retrospective study.
AB - AIM: Polypharmacy is a highly prevalent geriatric syndrome, and hospitalizations
can worsen it. The aim of the present study was to analyze the influence of
hospitalization on polypharmacy and indicators of quality of prescribing, and
their possible association with health outcomes. METHODS: A retrospective study
of 200 patients discharged from an acute geriatric unit was carried out.
Indicators of quality of prescription were registered at admission and discharge:
polypharmacy defined as >=5 medications, hyperpolypharmacy (>=10), potentially
inappropriate prescribing by Beers and Screening Tool of Older Persons'
potentially inappropriate Prescriptions (STOPP) criteria, potentially prescribing
omissions by Screening Tool to Alert doctors to the Right Treatment (START)
criteria, drug interactions and anticholinergic burden measured with the
Anticholinergic Risk Scale. Mortality, emergency room visits and hospital
admissions occurring during 6 months after discharge were also registered.
RESULTS: The total number of drugs increased at discharge (9.1 vs 10.1, P <
0.001), without increasing chronic medications (8.5 vs 8.3, P = 0.699). No
significant variations were observed in the prevalence of polypharmacy (86.5% vs
82.2%), potentially inappropriate prescribing (68.5% vs 71.5%), potential
prescribing omissions (58% vs 58%) or drug interactions (82.5% vs 83.5%).
Patients with anticholinergic drugs tended to increase, not reaching statistical
significance (39.5% vs 44.5%; P = 0.064). Polypharmacy was associated with
emergency room visits (OR 2.62, 95% CI 1.07-6.40; P = 0.034), and
hyperpolypharmacy with hospitalizations (OR 2.49, 95% CI 1.25-4.93; P = 0.009).
CONCLUSIONS: After hospitalization in an acute geriatric unit, the prevalence of
polypharmacy, potentially inappropriate prescribing, potential prescribing
omissions, interactions or anticholinergic drugs is still very high. Polypharmacy
is a risk factor for hospitalization and emergency room visits. Measuring
indicators of quality of prescription might be useful to design interventions to
optimize pharmacotherapy and improve health outcomes in elderly acute patients.
Geriatr Gerontol Int 2017; 17: 2354-2361.
PMID- 28422416
TI - Clot wave analysis and thromboembolic score in liver cirrhosis: two opposing
phenomena.
AB - INTRODUCTION: Prothrombin time (PT) and activated partial thromboplastin time
(aPTT) are abnormal but unreliable in cirrhotic patients to express their risk of
bleeding. However, these patients may also suffer from thrombotic episodes. In
order to investigate the dynamics of the formation of fibrin, the clot waveform
analysis (CWA) of aPTT was studied together with a score for the evaluation of
the thromboembolic risk. METHODS: CWA in terms of velocity (1st derivative),
acceleration (2nd derivatives) and density (Delta) of aPTT and the Padua
Prediction Score (PPS) for venous thromboembolism were studied in 191 cirrhotic
patients. RESULTS: CWA values were lower in the cirrhotic patients when compared
to the control groups. However, Delta, 1st and 2nd derivatives were higher in
cirrhotic patients with elevated PPS in comparison to those with a low PPS. The
1st derivative was significantly associated with a high PPS score (>4): OR: 2.66,
CI: 95% 1.23-5.78. CONCLUSIONS: Two opposing tendencies seem to be present in
cirrhotic disease: the first shows a weakness of clot formation while the second
a predisposition towards thrombosis, identified by the PPS.
PMID- 28422417
TI - Cranial irradiation in childhood mimicking neurofibromatosis type II.
AB - Neurofibromatosis type II (NF2) is a genetic disease characterized by bilateral
vestibular schwannomas (VS) and other nerve system tumors. However, such tumors
may be associated with environmental, rather than a genetic, etiology.
Individuals fulfilling the clinical criteria of NF2 who had been treated by head
ionized irradiation at a young age were compared for disease characteristics and
molecular analysis with non-irradiated sporadic NF2 cases. In the study cohort,
three of 33 sporadic adult cases fulfilling NF2 diagnostic criteria had a history
of early age cranial irradiation exposure. None of the irradiated patients had
bilateral VS compared with 73.3% of the non-irradiated individuals. One of the
irradiated patients had no VS, while none of the non-irradiated NF2 cases had
absence of VS. All of the irradiated individuals had brain meningiomas and
thyroid tumors compared with 47% and 0%, respectively, of the non-irradiated
individuals. Molecular analyses for NF2 mutations in blood of the irradiated
individuals failed to detect disease-causing mutations. This study suggest that
environmental factors may mimic NF2. Identifying such non-genetic cases
fulfilling clinical criteria of the genetic disease may be crucial for the
purposes of genetic counseling and patient management.
PMID- 28422418
TI - Factors associated with mucosal dryness in multiple regions and skin: A web-based
study in women.
AB - AIM: We hypothesized that feeling mucosal dryness in one body region and the skin
may be associated with dryness in other regions and that there are common
background factors for dryness. In an earlier web-based survey, we reported
prevalence figures of dry eyes, nose, mouth, skin, and vagina. In the present
study, additional analyses were made to investigate the factors associated with
dryness in each region, and simultaneous dryness in multiple regions. METHODS: A
web-based questionnaire was completed by 310 Japanese women. The questions
included dryness of the eyes, nose, mouth, vagina, and skin. Menopausal and other
symptoms were also addressed. Multiple logistic regression modeling was performed
to identify factors associated with dryness in each region and in multiple dry
regions. RESULTS: Dry eyes were associated with dryness in the nose and with
headache; dry nose was associated with dryness in the vagina and eyes; dry mouth
was associated with sticky mouth symptom and dryness of the nose; dry skin was
associated with use of xerogenic medications and vaginal discharge; and dryness
of the vagina was associated with vaginal itchiness and dry nose. Vaginal
discharge (odds ratio, 9.64; 95% confidence interval, 3.15-29.51) and sticky
mouth (odds ratio, 6.35; 95% confidence interval, 1.29-31.29) were further
associated with dryness in multiple regions. CONCLUSION: The present results
confirmed our study hypothesis by showing that dryness in one region was clearly
associated with that in another or in multiple regions. The result implies the
need for holistic diagnosis and counseling for patients with dryness complaints.
PMID- 28422419
TI - Carbohydrate Analogue Microarrays for Identification of Lectin-Selective Ligands.
AB - Fifty-five mono- and disaccharide analogues were prepared and used for the
construction of microarrays to uncover lectin-selective ligands. The microarray
study showed that two disaccharide analogues, 28' and 44', selectively bind to
Solanum tuberosum lectin (STL) and wheat germ agglutinin (WGA), respectively.
Cell studies indicated that 28' and 44' selectively block the binding of STL and
WGA to mammalian cells, unlike the natural ligand LacNAc, which suppresses
binding of both STL and WGA to cells.
PMID- 28422420
TI - A study of disseminated intravascular coagulation in acute leukemia reveals
markedly elevated D-dimer levels are a sensitive indicator of acute promyelocytic
leukemia.
AB - INTRODUCTION: While the presence of disseminated intravascular coagulation (DIC)
has been implicated in worse clinical outcome in acute leukemia, the relationship
between different subtypes of acute leukemia and the clinicopathologic features
of DIC has not been systematically well studied. METHODS: In this study, we
retrospectively reviewed 149 cases of newly diagnosed acute leukemia and assessed
the utility of evaluating red blood cell morphologic features, and coagulation
parameters in determining the presence of DIC as well as differentiating subtypes
of acute leukemia. RESULTS: Review of our cohort demonstrates a novel finding,
that elevated D-dimer concentrations >=19 000 ng/mL fibrinogen equivalent units
(FEU) are a sensitive diagnostic indicator of acute promyelocytic leukemia (APL)
with moderate specificity, sensitivity 96%, specificity 92% in acute leukemia
subtyping. Similar to other studies, APL showed an increased incidence of DIC (P
< 0.01) compared to other subtypes of acute leukemia. Surprisingly, the presence
of schistocytes on the peripheral blood smear was not a statistically significant
indicator of DIC, sensitivity of 36% and specificity of 89%. Finally, the
presence of DIC was not a significant indicator of poorer prognosis amongst all
patients with AML. CONCLUSION: Overall we identify elevated D-dimer
concentrations >=19 000 ng/mL FEU are a sensitive indicator of acute
promyelocytic leukemia (APL), with a sensitivity of 96% and specificity of 92% in
the subtyping of acute leukemias, and that the presence of schistocytes in
peripheral blood smears is not a diagnostically sensitive screening test for DIC
with a sensitivity of 36%.
PMID- 28422421
TI - Results of a 10-year survey of workload for 10 treatment vaults at a high
throughput comprehensive cancer center.
AB - The workload for shielding purposes of modern linear accelerators (linacs)
consists of primary and scatter radiation which depends on the dose delivered to
isocenter (cGy) and leakage radiation which depends on the monitor units (MUs).
In this study, we report on the workload for 10 treatment vaults in terms of dose
to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions
(Txs), as well as, use factors (U) and modulation factors (CI) for different
treatment techniques. The survey was performed for the years between 2006 and
2015 and included 16 treatment machines which represent different generations of
Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at
different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6
and 15 MV x-rays). An institutional review board (IRB) approval was acquired to
perform this study. Data regarding patient workload, dose to isocenter, number of
monitor units delivered, beam energies, gantry angles, and treatment techniques
were exported from an ARIA treatment management system (Varian Medical Systems,
Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in
Matlab. The average (+/- std-dev) number of treatment sessions, dose to
isocenter, and number of monitor units delivered per week per machine in 2006 was
119 +/- 39 Txs, (300 +/- 116) * 102 cGys, and (78 +/- 28) * 103 MUs respectively.
In contrast, the workload in 2015 was 112 +/- 40 Txs, (337 +/- 124) * 102 cGys,
and (111 +/- 46) * 103 MUs. 60% of the workload (cGy) was delivered using 6 MV
and 30% using 15 MV while the remaining 10% was delivered using electron beams.
The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (+/- 3.4) and 4.6 (+/-
1.6) respectively. Use factors using 90 degrees gantry angle intervals were
equally distributed (~0.25) but varied considerably among different treatment
techniques. The workload, in terms of dose to isocenter (cGy) and subsequently
monitor units (MUs), has been steadily increasing over the past decade. This
increase can be attributed to increased use of high dose hypo-fractionated
regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require
higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile,
the patient workload in terms of treatment sessions per week remained relatively
constant. The findings of this report show that variables used for shielding
purposes still fall within the recommendation of NCRP Report 151.
PMID- 28422422
TI - Psychopathology and social functioning of 42 subjects from a Danish ultra high
risk cohort.
AB - AIM: To make a thorough characterization of the co-morbidity, psychopathology and
demographics in the first Danish ultra high-risk (UHR) sample. METHOD: Forty-two
UHR subjects went through comprehensive interviews assessing their
psychopathology, psychiatric disorders, substance use and family history of
psychiatric disorders. RESULTS: All UHR subjects met the criteria of at least 1
axis I diagnosis in the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV) and met on average four diagnoses (both axis I and II),
mostly within the areas of depression, anxiety and substance abuse. A total of
48% had schizotypal personality disorder and 19% had borderline personality
disorder. Level of functioning was low with a mean score on the Social and
Occupational Functioning Assessment Scale corresponding to "major impairment in
several areas," and mean scores in the Global Functioning: Social and Role scales
between "moderate impairment in social functioning" and "very serious impairment
independently." Forty-seven percent were unemployed and 29% on sick leave. Fifty
five percent relied financially on public support. CONCLUSION: As seen in
previous UHR populations, Danish UHR subjects had low function socio-economically
and met criteria of several psychiatric diagnoses, suggesting that they require
pharmacological and non-pharmacological psychiatric treatment as well as
vocational and educational guidance and support.
PMID- 28422423
TI - Erratum.
PMID- 28422424
TI - Pregnancy outcomes in women with different doses of corticosteroid
supplementation during labor and delivery.
AB - AIM: The aim of this study was to report the pregnancy outcomes of women who
received different doses of corticosteroid supplementation during labor and
delivery. METHODS: We conducted a retrospective review of 102 pregnant women who
received oral corticosteroid therapy, delivered at Osaka University Hospital, and
were administered intravenous corticosteroid supplementation during labor and
delivery. From January 2008 to May 2012, 47 women were administered a high dose
of corticosteroids (HD group). From June 2012 to December 2016, 55 women were
given a low dose of corticosteroids (LD group). RESULTS: There were no
significant differences in the patient characteristics between the two groups.
The most frequent disease was systemic lupus erythematosus (30/102; 29.4%). Most
women used prednisolone for more than 1 year (91/102; 89.2%) and at a dose of
more than 5 mg/day (88/102; 86.3%). The total intravenous dose of hydrocortisone
during labor and delivery +/- standard deviation was 233.5 +/- 129.4 mg (HD
group) and 143.4 +/- 38.1 mg (LD group), exhibiting a significantly larger dose
in the HD group. No patients suffered an adrenal deficiency and there were no
significant differences in the hemodynamics. There were three cases of puerperal
endometritis, two patients with hyperglycemia, and one wound infection in the HD
group, whereas one case of puerperal endometritis in the LD group. There were no
significant differences in the neonatal outcomes. CONCLUSION: Pregnancy outcomes
did not differ between the high and low doses of corticosteroid supplementation
during labor and delivery.
PMID- 28422425
TI - Negativization of viremia prior to liver transplant reduces early allograft
dysfunction in hepatitis C-positive recipients.
AB - Although early allograft dysfunction (EAD) negatively impacts survival from the
first months following liver transplantation (LT), direct-acting antiviral agents
(DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the
EAD definition best predicting 90-day graft loss and identified EAD risk factors
in HCV-positive recipients. From November 2002 to June 2016, 603 HCV-positive
patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV-negative
donors. The median recipient Model for End-Stage Liver Disease (MELD) score was
15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV
RNA negative; negativization was achieved and maintained by pre-LT antiviral
therapy (61 patients) or pre-LT plus a pre-emptive post-LT course (16 patients);
60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3
different EAD definitions: (1) bilirubin >= 10 mg/dL or international normalized
ratio >= 1.6 on day 7 after LT or aspartate aminotransferase or alanine
aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on
days 2-7 after LT; and (3) MELD >= 19 on day 5 after LT. EAD defined by MELD >=
19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9)
likelihood ratio to predict 90-day graft loss. At 90 days after LT, 9.2% of
recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P <
0.001). At multivariate analysis, considering variables available at LT, MELD at
LT of >25 (OR = 7.4) or 15-25 (OR = 3.2), graft macrovesicular steatosis >= 30%
(OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0),
earlier LT era (OR = 1.8), and cold ischemia time >= 8 hours (OR = 1.8) were
significant risk factors for EAD. In conclusion, in HCV-positive patients, MELD
>= 19 on day 5 after LT best predicts 90-day graft loss. Preventing graft
infection by pre-/peri-LT antiviral therapy reduces EAD incidence and could be
most beneficial in high-MELD patients and recipients of suboptimal grafts. Liver
Transplantation 23 915-924 2017 AASLD.
PMID- 28422426
TI - Dinosaurs, Chameleons, Humans, and Evo-Devo Path: Linking Etienne Geoffroy's
Teratology, Waddington's Homeorhesis, Alberch's Logic of "Monsters," and
Goldschmidt Hopeful "Monsters".
AB - Since the rise of evo-devo (evolutionary developmental biology) in the 1980s, few
authors have attempted to combine the increasing knowledge obtained from the
study of model organisms and human medicine with data from comparative anatomy
and evolutionary biology in order to investigate the links between development,
pathology, and macroevolution. Fortunately, this situation is slowly changing,
with a renewed interest in evolutionary developmental pathology (evo-devo-path)
in the past decades, as evidenced by the idea to publish this special, and very
timely, issue on "Developmental Evolution in Biomedical Research." As all of us
have recently been involved, independently, in works related in some way or
another with evolution and developmental anomalies, we decided to join our
different perspectives and backgrounds in the present contribution for this
special issue. Specifically, we provide a brief historical account on the study
of the links between evolution, development, and pathologies, followed by a
review of the recent work done by each of us, and then by a general discussion on
the broader developmental and macroevolutionary implications of our studies and
works recently done by other authors. Our primary aims are to highlight the
strength of studying developmental anomalies within an evolutionary framework to
understand morphological diversity and disease by connecting the recent work done
by us and others with the research done and broader ideas proposed by authors
such as Etienne Geoffroy Saint-Hilaire, Waddington, Goldschmidt, Gould, and Per
Alberch, among many others to pave the way for further and much needed work
regarding abnormal development and macroevolution.
PMID- 28422427
TI - Is motor imagery different in catatonic schizophrenia?
AB - Catatonic schizophrenia, a rare subtype in this disease group, is characterized
by motor disturbances. The current study investigated the reactivity of
electroencephalographic mu rhythm in a motion imagery task in two single cases of
first-episode catatonic schizophrenia, assuming they would show less mu rhythm
reduction compared to paranoid schizophrenic patients and healthy controls.
PMID- 28422428
TI - Identification of Transthyretin Fibril Formation Inhibitors Using Structure-Based
Virtual Screening.
AB - Transthyretin (TTR) is the primary carrier for thyroxine (T4 ) in cerebrospinal
fluid and a secondary carrier in blood. TTR is a stable homotetramer, but certain
factors, genetic or environmental, could promote its degradation to form amyloid
fibrils. A docking study using crystal structures of wild-type TTR was planned;
our aim was to design new ligands that are able to inhibit TTR fibril formation.
The computational protocol was thought to overcome the multiple binding modes of
the ligands induced by the peculiarity of the TTR binding site and by the
pseudosymmetry of the site pockets, which generally weaken such structure-based
studies. Two docking steps, one that is very fast and a subsequent step that is
more accurate, were used to screen the Aldrich Market Select database. Five
compounds were selected, and their activity toward inhibiting TTR fibril
formation was assessed. Three compounds were observed to be actives, two of which
have the same potency as the positive control, and the other was found to be a
promising lead compound. These results validate a computational protocol that is
able to archive information on the key interactions between database compounds
and TTR, which is valuable for supporting further studies.
PMID- 28422430
TI - AAPM Spring Clinical Meeting - Abstracts.
PMID- 28422429
TI - Development of the headspace Family and Friends Satisfaction Scale: Findings from
a pilot study.
AB - AIMS: The primary aim of this pilot study was to determine the psychometric
properties of the 18-item headspace Family and Friends Satisfaction Scale
(hFAFSS). METHODS: During August 2015, staff from 22 headspace centres approached
family members and friends of young people attending headspace to complete the
hFAFSS. Principal components analysis with oblique Promin rotation and polychoric
correlations were used to assess the factor structure of the hFAFSS. RESULTS:
There were 277 usable responses. Satisfaction was high, resulting in little
variance. Parallel analyses suggested that the scale items tapped a single factor
(68% of variance). CONCLUSIONS: This study is one of the first attempts to
measure the satisfaction of family and friends with primary care-based youth
mental health services. Satisfaction of family members and friends was shown to
be high, but limited variance restricts the usability of the hFAFSS as an
evaluation measure, and revision and further testing is needed.
PMID- 28422431
TI - Effect of Empagliflozin on Tacrolimus-Induced Pancreas Islet Dysfunction and
Renal Injury.
AB - An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in
type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus
(TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced
pancreatic islet dysfunction and renal injury in an experimental model of TAC
induced DM and in vitro. TAC induced a twofold increase in SGLT-2 expression,
while Em decreased SGLT-2 expression and further increased urinary glucose
excretion compared to the TAC group. Em reduced hyperglycemia and increased
plasma insulin level, pancreatic islet size, and glucose-stimulated insulin
secretion compared to the TAC group. In kidney, Em alleviated TAC-induced renal
dysfunction and decreased albumin excretion and histological injury compared with
the TAC group. Increased oxidative stress and apoptotic cell death by TAC was
remarkably decreased with Em in serum and pancreatic and renal tissues. In in
vitro study, TAC decreased cell viability and increased reactive oxygen species
(ROS) production in both insulin-secreting beta-cell derived (INS-1) and human
kidney-2 (HK-2) cell lines. Addition of Em increased cell viability and decreased
ROS production in HK-2 but not in INS-1 cell lines. This suggests that Em is
effective in controlling TAC-induced hyperglycemia and has direct protective
effect on TAC-induced renal injury.
PMID- 28422432
TI - JA but not JA-Ile is the cell-nonautonomous signal activating JA mediated
systemic defenses to herbivory in Nicotiana attenuata.
AB - The whole-plant activation of defense responses to wounding and herbivory
requires systemic signaling in which jasmonates (JAs) play a pivotal role. To
examine the nature of the slower cell-nonautonomous as compared to the rapid cell
autonomous signal in mediating systemic defenses in Nicotiana attenuata,
reciprocal stem grafting-experiments were used with plants silenced for the JA
biosynthetic gene ALLENE OXIDE CYCLASE (irAOC) or plants transformed to create JA
sinks by ectopically expressing Arabidopsis JA-O-methyltransferase (ovJMT). JA
impaired irAOC plants were defective in the cell-nonautonomous signaling pathway
but not in JA transport. Conversely, ovJMT plants abrogated the production of a
graft-transmissible JA signal. Both genotypes displayed unaltered cell-autonomous
signaling. Defense responses (17-hydroxygeranyllinalool diterpene glycosides,
nicotine, and proteinase inhibitors) and metabolite profiles were differently
induced in irAOC and ovJMT scions in response to graft-transmissible signals from
elicited wild type stocks. The performance of Manduca sexta larvae on the scions
of different graft combinations was consistent with the patterns of systemic
defense metabolite elicitations. Taken together, we conclude that JA and possibly
MeJA, but not JA-Ile, either directly functions as a long-distance transmissible
signal or indirectly interacts with long distance signal(s) to activate systemic
defense responses.
PMID- 28422433
TI - Rigid Nonfullerene Acceptors Based on Triptycene-Perylene Dye for Organic Solar
Cells.
AB - Three kinds of nonconjugated rigid perylene bisimide (PBI) derivatives based on a
triptycene core were designed, synthesized and characterized. The unique three
dimensional (3D) conformation of triptycene could enable formation of polymer
with the favorable morphology for organic polymer solar cells (PSCs) by relieving
the self-aggregation of rigid PBI units. The low-lying LUMO energy levels of
these compounds demonstrated that they are very suitable for use as acceptors in
organic solar cells. A higher power conversion efficiency (PCE) of 6.15 % was
obtained for the blend film using the compound with two PBI units (T-2) as the
acceptor and commercial poly[[4,8-bis[5-(2-ethylhexyl)thiophene-2-yl]benzo[1,2
b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4
b]thiophenediyl]] (PCE-10) as the electron donor.
PMID- 28422434
TI - Rat Hindlimb Cryopreservation and Transplantation: A Step Toward "Organ Banking".
AB - In 2016, over 5 million reconstructive procedures were performed in the United
States. The recent successes of clinical vascularized composite
allotransplantations, hand and face transplantations included, established the
tremendous potential of these life-enhancing reconstructions. Nevertheless, due
to limited availability and lifelong immunosuppression, application is limited.
Long-term banking of composite transplants may increase the availability of
esthetically compatible parts with partial or complete HLA matching, reducing the
risk of rejection and the immunosuppressive burden. The study purpose was to
develop efficient protocols for the cryopreservation and transplantation of a
complete rodent limb. Directional freezing is a method in which a sample is
cooled at a constant-velocity linear temperature gradient, enabling precise
control of the process and ice crystal formation. Vitrification is an alternative
cryopreservation method in which the sample solidifies without the formation of
ice crystals. Testing both methods on a rat hindlimb composite tissue
transplantation model, we found reliable, reproducible, and stable ways to
preserve composite tissue. We believe that with further research and development,
cryopreservation may lead to composite tissue "banks." This may lead to a
paradigm shift from few and far apart emergent surgeries to wide-scale, well
planned, and better-controlled elective surgeries.
PMID- 28422435
TI - Blue organic light-emitting diodes based on fluorene-bridged quinazoline and
quinoxaline derivatives.
AB - Two blue emitters based on fluorene-bridged quinazoline and quinoxaline
derivatives were prepared via the Suzuki reaction. Their photoluminescent
properties were investigated. Furthermore, theoretical studies on these materials
using the density functional theory calculation were conducted. To explore their
electroluminescent properties, multilayered organic light-emitting diodes were
fabricated with the following device structure: indium-tin-oxide (180 nm)/4,4'
bis(N-(1-naphthyl)-N-phenylamino)biphenyl (50 nm)/blue emitting materials (1 and
2) (30 nm)/bathophenanthroline (35 nm)/8-hydroxy-quinolinato lithium (2 nm)/Al
(100 nm). Two devices showed efficient blue emission with the external quantum
efficiencies of 1.58% and 1.30%, respectively, at 20 mA/cm2 , and Commission
Internationale dEclairage coordinates of (0.18, 0.24) and (0.19, 0.27) at 6.0 V.
These results suggest that the self-aggregation properties of emitters would have
considerable effects on their photoluminescent and electroluminescent properties.
PMID- 28422437
TI - Prognostic value of Hutchinson's sign for ocular involvement in herpes zoster
ophthalmicus.
PMID- 28422436
TI - Tandem Transformation of Nitro Compounds into N-Methylated Amines: Greener
Strategy for the Utilization of Methanol as a Methylating Agent.
AB - A simple air- and moisture-stable, highly efficient ruthenium NNN pincer complex
is reported for the first time to catalyze the tandem transformation of various
aromatic and aliphatic nitro compounds into the corresponding N-methylated amines
in up to 98 % yield by using methanol as a green methylating agent. Gram-scale
reactions of challenging nitro substrates demonstrated the practical application
aspects of this catalytic system. Importantly, the N-methylamine moiety could be
smoothly introduced to various complex molecular structures without using any
expensive palladium/phosphine/amine-based cross-coupling reactions.
PMID- 28422439
TI - Does touch inhibit visual imagery? A case study on acquired blindness.
AB - In a single-case study of acquired blindness, differential brain activation
patterns for visual imagery of familiar objects with and without tactile
exploration as well as of tactilely explored unfamiliar objects were observed.
Results provide new insight into retrieval of visual images from episodic memory
and point toward a potential tactile inhibition of visual imagery.
PMID- 28422440
TI - Blood parameters of preterm neonates: postnatal evolution according to
gestational age.
AB - INTRODUCTION: The blood count provides qualitative and quantitative essential
information on bloodlines. Reference hematologic parameters have been established
in children and neonates, but few data are available regarding the premature
population during the first month of life. The main objective of this study was
to establish normative values for blood parameters for premature infants born
between 26 and <37 weeks of gestation, during the first month of life, taking
into account gestational and postnatal age and treatments that can impact the
threshold values. METHODS: A single-center retrospective study was conducted
based on the clinical and laboratory data of preterm infants born between January
1, 2012 and December 31, 2013 and hospitalized in the intensive care, neonatal,
and maternity units of University Hospital of Saint Etienne (France). Data were
collected by crossing the PMSI database (date of birth and gestational age), the
administrative patient database (IPP), and the pre-analytical laboratory
database. Anthropometric and clinical data were extracted for both mother and
child. The samples were all made from central or peripheral venous blood. All
blood parameters were taken into account. RESULTS: The degree of prematurity is a
factor greatly influencing the values of the blood parameters at birth. All three
blood lines increase in proportion to gestational age. We were able to highlight
for some blood parameters specific kinetic profiles according to gestational age.
CONCLUSION: Blood parameters of preterm neonates depend on both the degree of
prematurity, postnatal age, and perinatal treatments. A good knowledge of these
physiological variations may help target transfusion or therapeutic indications
in everyday practice.
PMID- 28422438
TI - Moyamoya syndrome in children with neurofibromatosis type 1: Italian-French
experience.
AB - Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children
with neurofibromatosis type 1 (NF1). In this study, we clinically,
radiologically, and genetically examined a cohort that was not previously
described, comprising European children with NF1 and MMS. The NF1 genotyping had
been registered. This study included 18 children. The mean age was 2.93 +/- 3.03
years at the NF1 diagnosis and 7.43 +/- 4.27 years at the MMS diagnosis. In seven
patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was
performed in 10 patients due to clinical symptoms, including headache (n = 6),
cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining
eight children (47%) had MMS diagnosed incidentally. Sixteen children were
characterized molecularly. The features of MMS were similar between patients with
and without NF1. Additionally, the NF1 phenotype and genotype were similar
between children with and without MMS. Interestingly, three children experienced
tumors with malignant histology or behavior. The presence of two first cousins in
our cohort suggested that there may be potential genetic factors, not linked to
NF1, with an additional role respect of NF1 might play a role in MMS
pathogenesis. The incidental diagnosis of MMS, and the observation that, among
children with NF1, those with MMS were clinically indistinguishable from those
without MMS, suggested that it might be worthwhile to add an angiographic
sequence to brain MRIs requested for children with NF1. A MMS diagnosis may
assist in properly addressing an NF1 diagnosis in very young children who do not
fulfill diagnostic criteria.
PMID- 28422441
TI - Recent Advances of Electrospun Nanofibrous Membranes in the Development of
Chemosensors for Heavy Metal Detection.
AB - It is critical to detect and analyze the heavy metal pollutions in environments
and foods. Chemosensors have been widely investigated for fast detection of
analytes such as heavy metals due to their unique advantages. In order to improve
the detection sensitivity of chemosensors, recently electrospun nanofibrous
membranes (ENMs) have been explored for the immobilization of chemosensors or
receptors due to their high surface-to-volume ratio, high porosity, easiness of
fabrication and functionalization, controllability of nanofiber properties, low
cost, easy detection, no obvious pollution to the detection solution, and easy
post-treatment after the detection process. The purpose of this review is to
summarize and guide the development and application of ENMs in the field of
chemosensors for the detection of analytes, especially heavy metals. First, heavy
metals, chemosensors, and four types of preparation methods for ENM-immobilized
chemosensors/receptors are briefly introduced. And then, ENM-immobilized
chemosensors/receptors and their application progresses for optical, electro, and
mass detections of heavy metals are reviewed according to the four types of
preparation methods. Finally, the application of ENM-immobilized
chemosensors/receptors is summarized and an outlook is provided. The review will
provide an instruction to the research and development of ENM-immobilized
chemosensors/receptors for the detection of analytes.
PMID- 28422442
TI - Effect of hepatitis B virus subgenotype on antiviral response in nucleoside
treated hepatitis B envelope antigen-positive patients.
AB - AIM: Previous studies have reported that hepatitis B virus (HBV) genotype is not
a predictor of treatment response with nucleos(t)ide analog therapy. However, the
impact of subgenotype on treatment response is unknown. The aim of this study is
to identify the effect of HBV subgenotype on treatment response. METHODS: In this
retrospective study, the derivation dataset comprised patients from the EFFORT
study (NCT00962533) telbivudine monotherapy group; patients infected with
genotypes B or C from the GLOBE (NCT00057265) and 015 (NCT00131742) studies
formed the validation dataset. The HBV subgenotypes were determined using
phylogenetic analysis based on the surface or overlapping polymerase gene.
Molecular modeling was used to investigate relationships between positions of the
substitutions within reverse transcriptase and genotypic resistance. RESULTS: Of
the patients in the derivation dataset, 110, 24, 162, and 1 patients were
classified as having HBV subgenotypes B2, C1, C2, or other, respectively,
compared to 222, 146, 282, and 51 in the validation dataset, respectively.
Patients infected with subgenotype C1 showed a higher virologic response rate and
hepatitis B envelope antigen seroconversion rate, and lower genotypic resistance
rate than those infected with subgenotypes B2 and C2. Patients with genotypic
resistance to telbivudine with subgenotype C1 showed fewer secondary mutations.
The crystal structure model of reverse transcriptase showed that these secondary
mutations were located around the YMDD motif, which possibly influenced the
chance of mutations at rtM204. CONCLUSION: Hepatitis B virus subgenotype C1 is
associated with better antiviral response to nucleoside analogs in hepatitis B
envelope antigen-positive patients than B2 and C2 subgenotypes. The exact
mechanism needs to be explored further.
PMID- 28422443
TI - Role of CD200 in differential diagnosis of mature B-cell neoplasm.
AB - INTRODUCTION: CD 200 is a type I immunoglobulin super family membrane
glycoprotein, which is expressed in various mature B-cell neoplasm (MBN). This
study aimed at analyzing the expression pattern of CD200 by flow cytometry
immunophenotyping (FCI) and to evaluate its utility in narrowing down the
differential diagnosis of MBN, particularly in low-grade lymphomas. METHODS: A
total of 160 samples were evaluated by FCI over a period of 2 years (July 2014
June 2016), by a panel of antibodies including CD200. The mean fluorescence
intensity (MFI) of CD200 in the neoplastic population was noted and compared
among several groups of MBN. RESULTS: All the 98 cases of chronic lymphocytic
leukemia (CLL), five being CD23-negative, expressed CD200 with moderate-to-bright
intensity (median MFI: 1174). None of the 24 mantle cell lymphoma (MCL) cases,
two being CD23-positive, expressed CD200 (median MFI: 10). All six hairy cell
leukemia (HCL) cases expressed CD200. CD200 expression in HCL was brightest among
all the MBNs, with a median MFI of 5050. Other MBN (n = 32) expressed CD200 in a
proportion of cases and with variable intensity, usually dimmer than CLL.
CONCLUSION: CD200 has a valid role in differentiating CLL from MCL, especially in
the cases with immunophenotypic overlap. HCL has a consistent and brightest
expression of CD200. It would be prudent to include CD200 in the primary panel of
antibodies for MBN analysis.
PMID- 28422444
TI - Validation of the Mandarin Chinese Version of the Pain Sensitivity Questionnaire.
AB - BACKGROUND AND AIM: The Pain Sensitivity Questionnaire (PSQ), a self-reported
scale, has been used to assess the pain sensitivity level in a Caucasian
population. However, a validated Mandarin Chinese version of the PSQ is not
available. This study was aimed to translate the PSQ into Mandarin Chinese (PSQ
C) and validate it to measure pain sensitivity among Chinese people. METHODS: The
English version of the PSQ has been translated into Mandarin Chinese (PSQ-C),
according to the standard steps of cross-cultural adaptation of self-reported
scales. Three of the 17 items were revised owing to cultural adaptation. The
final version was validated on a population of 182 Chinese people in Changsha
City, China, during October to December 2015. The participants underwent
electrical experimental pain testing. The psychometric properties of the PSQ-C
and its subscales were examined. RESULTS: The Cronbach's alpha coefficients for
the PSQ-C-total, PSQ-C-moderate, and PSQ-C-minor were 0.90, 0.86, and 0.81,
respectively. Acceptable test-retest reliability, content validity, and construct
validity were demonstrated. Concurrent validity was shown via significant
positive correlations between PSQ-C scores and perceived pain intensity at pain
threshold and during pain stimulation with a fixed intensity. Convergent validity
was shown via significant positive correlations between Pain Catastrophizing
Scale scores and PSQ-C scores. Known group validity was demonstrated via higher
PSQ-C-total and PSQ-C-moderate scores among those with high neuroticism scores.
These results indicate that the PSQ-C has reasonably good psychometric
properties, similar to the original English and German versions. CONCLUSION: The
PSQ-C is a reliable and useful tool to assess pain sensitivity levels in a
Chinese population.
PMID- 28422445
TI - Transcriptional profiling of SHR/NCrl prefrontal cortex shows hyperactivity
associated genes responsive to amphetamine challenge.
AB - Several studies suggest a strong genetic component of attention
deficit/hyperactivity disorder (ADHD), a complex neurodevelopmental disorder
characterized by inappropriate levels of hyperactivity, impulsivity and
inattention. Determining specific genetic risk variants for each symptom
dimension of ADHD may aid in the identification of the biological risk factors of
the disorder. In this study, we explored the potential genetic underpinnings of
the hyperactive phenotype of ADHD. To this end, we examined differentially
expressed genes (DEGs) in the prefrontal cortex (PFC) of SHR/NCrl, an animal
model of ADHD, compared with its genetic control, the Wistar Kyoto (WKY/NCrl) rat
and the Wistar rat, strain used to represent the 'normal' heterogeneous
population. Relative to WKY/NCrl and Wistar controls, SHR/NCrl showed
hyperactivity in the open-field test. Treatment with the ADHD drug, amphetamine
(AMPH) reduced hyperactivity in SHR/NCrl. Meanwhile, AMPH increased locomotor
activity in WKY/NCrl and Wistar rats. Gene expression analysis found 21 common
upregulated and 36 downregulated genes in the PFC of drug-naive SHR/NCrl when
compared with WKY/NCrl and Wistar rats. Of these DEGs, expression levels of two
genes, Atxn7 and Per2, which are involved in transcription and circadian rhythm,
respectively, were downregulated following AMPH treatment in SHR/NCrl.
Quantitative real-time-polymerase chain reaction analyses verified expression
patterns of these genes in the PFC of drug-naive and AMPH-treated SHR/NCrl. The
present findings indicate genetic risk variants that may be associated with the
hyperactive phenotype in ADHD. Further studies are warranted to establish the
roles of Atxn7 and Per2 in mediating hyperactivity.
PMID- 28422446
TI - Fusion of a family 20 carbohydrate-binding module (CBM20) with cyclodextrin
glycosyltransferase of Geobacillus sp. CHB1 improves catalytic efficiency.
AB - Cyclodextrin glycosyltransferase (CGTase) is an important industrial enzyme for
production of cyclodextrins (CDs) from starch by intramolecular
transglycosylation. CGTase consists of five domains labeled A to E. For
optimizing catalytic activity of CGTase, CGTase of Geobacillus sp. was fused with
the family 20 carbohydrate-binding module (CBM) of the Bacillus circulans strain
251 CGTase. The CBMbc251 that has a low binding free energy with maltohexaose,
was selected by in silico design. Then the fusion enzyme, CGTDeltaE-CBMbc251, was
constructed by fusing the CBMbc251 to the C-terminal region of CGTDeltaE. The
fusion enzyme displayed an even greater enhancement of total alpha-cyclization
activity (40.2%) and gamma-cyclization activity (181.58%). Optimal reaction pH
range was wilder and the thermal stability was better under 50 and 60 degrees C.
Compared to the wild-type CGTase, the fusion enzyme showed a remarkable decrease
in Km and a slight alteration in Vmax. The enhancement of soluble starch
catalytic efficiency might be due to the changes of substrate binding ability in
the critical substrate binding sites between the CBM and starch granule.
PMID- 28422447
TI - LC-MS/MS and chiroptical spectroscopic analyses of multidimensional metabolic
systems of chiral thalidomide and its derivatives.
AB - Enantiomeric thalidomide undergoes various kinds of biotransformations including
chiral inversion, hydrolysis, and enzymatic oxidation, which results in several
metabolites, thereby adding to the complexity in the understanding of the nature
of thalidomide. To decipher this complexity, we analyzed the multidimensional
metabolic reaction networks of thalidomide and related molecules in vitro.
Characteristic patterns in the amount of various metabolites of thalidomide and
related molecules generated during a combination of chiral inversion, hydrolysis,
and hydroxylation were observed using liquid chromatography-tandem mass
spectrometry and chiroptical spectroscopy. We found that monosubstituted
thalidomide derivatives exhibited different time-dependent metabolic patterns
compared with thalidomide. We also revealed that monohydrolyzed and
monohydroxylated metabolites of thalidomide were likely to generate mainly by a C
5 oxidation of thalidomide and subsequent ring opening of the hydroxylated
metabolite. Since chirality was conserved in most of these metabolites during
metabolism, they had the same chirality as that of nonmetabolized thalidomide.
Our findings will contribute toward understanding the significant pharmacological
effects of the multiple metabolites of thalidomide and its derivatives.
PMID- 28422448
TI - Benefits of clinical facilitators on improving stroke care in acute hospitals: a
new programme for Australia.
AB - BACKGROUND: Care gaps for stroke lead to preventable disability and deaths. The
Victorian State Government implemented a programme of employing clinical
Facilitators on a fixed-term basis for up to 3 years (2008-2011) in eight
hospitals to improve stroke care. The Facilitators were to establish stroke units
where absent, implement evidence-based management protocols and provide staff
education within an agreed work plan. AIM: To determine if the Facilitator role
was associated with improved stroke care and to describe factors supporting or
mitigating enhancements to care. METHODS: A mixed methods design was employed
with historical control using patient-level audit data (pre-Facilitator: n = 600;
post-Facilitator: n = 387) and qualitative data from independently conducted
semistructured interviews with hospital staff, including clinicians, executives
and facilitators (n = 10 focus groups; 75 respondents). RESULTS: Stroke units,
clinical pathways and outpatient clinics for managing transient ischaemic attacks
(TIA) were established. Compared with the pre-Facilitator period, significant
increases in patient access to stroke unit care (53% vs 86%, P < 0.001) and
intravenous thrombolysis (2% vs 9%, P < 0.001) were achieved. Hospital staff
reported that the Facilitator was integral to system improvements by fostering
communication, encouraging team motivation and cohesiveness and increasing
interest in stroke care. Ongoing barriers included limited resources to operate
TIA clinics effectively, staff turnover requiring ongoing education,
inconsistency in compliance with protocols and, in some hospitals, the need for
formalised medical leadership. CONCLUSION: Fixed-term employment of Facilitators
was effective in positively influencing stroke care in hospitals through a range
of change management strategies where stroke-specific expertise had been
previously limited.
PMID- 28422449
TI - Enhanced chemiluminescence for trazodone trace analysis based on acidic
permanganate oxidation in concurrent presence of rhodamine 6G.
AB - A new sensitized chemiluminescence method by acidic permanganate oxidation was
developed for the sensitive determination of trazodone. A fluorescent dye as used
rhodamine 6G to increase a chemiluminescence intensity. Under optimum conditions,
the liner range of the calibration curve was obtained for 1-5000 nmol/L. The
limit of detection was calculated from 3sigma of a blank was 0.23 nmol/L. The
coexistent ions and substances had no interference with the chemiluminescence
measurement. The chemiluminescence spectra were measured to elucidate a possible
mechanism for the system. The present method was satisfactorily used in the
determination of the drugs in pharmaceutical samples and animal serums.
PMID- 28422450
TI - Erratum to Prenatal diagnosis of focal dermal hypoplasia: Report of three fetuses
and review of the literature.
PMID- 28422451
TI - Multiunit Sequences in First Language Acquisition.
AB - Theoretical and empirical reasons suggest that children build their language not
only out of individual words but also out of multiunit strings. These are the
basis for the development of schemas containing slots. The slots are putative
categories that build in abstraction while the schemas eventually connect to
other schemas in terms of both meaning and form. Evidence comes from the nature
of the input, the ways in which children construct novel utterances, the
systematic errors that children make, and the computational modeling of
children's grammars. However, much of this research is on English, which is
unusual in its rigid word order and impoverished inflectional morphology. We
summarize these results and explore their implications for languages with more
flexible word order and/or much richer inflectional morphology.
PMID- 28422452
TI - Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan
beads.
AB - S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was
produced using immobilized lipase. The lipase enzyme was immobilized on chitosan
beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order
to find an appropriate support for the hydrolysis reaction of racemic naproxen
methyl ester, the conversion and enantioselectivity for all carriers were
compared. In addition, effects of the volumetric ratio of two phases in different
organic solvents, addition of cosolvent and surfactant, optimum pH and
temperature, reusability, and inhibitory effect of methanol were investigated.
The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to
organic phase. Various water miscible and water immiscible solvents were
examined. Finally, isooctane was chosen as an organic solvent, while 2
ethoxyethanol was added as a cosolvent in the organic phase of the reaction
mixture. The optimum reaction conditions were determined to be 35 degrees C, pH
7, and 24 h. Addition of Tween-80 in the organic phase increased the
accessibility of immobilized enzyme to the reactant. The optimum organic phase
compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80
were 3:7 and 0.1% (v/v/v), respectively. The best conversion and
enantioselectivity of immobilized enzyme using chitosan beads activated by
glutaraldehyde were 0.45 and 185, respectively.
PMID- 28422453
TI - How many roads lead to cohesinopathies?
AB - Genetic mapping studies reveal that mutations in cohesion pathways are
responsible for multispectrum developmental abnormalities termed cohesinopathies.
These include Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), and
Warsaw Breakage Syndrome (WABS). The cohesinopathies are characterized by
overlapping phenotypes ranging from craniofacial deformities, limb defects, and
mental retardation. Though these syndromes share a similar suite of phenotypes
and arise due to mutations in a common cohesion pathway, the underlying
mechanisms are currently believed to be distinct. Defects in mitotic failure and
apoptosis i.e. trans DNA tethering events are believed to be the underlying cause
of RBS, whereas the underlying cause of CdLS is largely modeled as occurring
through defects in transcriptional processes i.e. cis DNA tethering events. Here,
we review recent findings described primarily in zebrafish, paired with
additional studies in other model systems, including human patient cells, which
challenge the notion that cohesinopathies represent separate syndromes. We
highlight numerous studies that illustrate the utility of zebrafish to provide
novel insights into the phenotypes, genes affected and the possible mechanisms
underlying cohesinopathies. We propose that transcriptional deregulation is the
predominant mechanism through which cohesinopathies arise. Developmental Dynamics
246:881-888, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422454
TI - Childhood maltreatment and adulthood poor sleep quality: a longitudinal study.
AB - BACKGROUND: Available evidence from cross-sectional studies suggests that
childhood maltreatment may be associated with a range of sleep disorders.
However, these studies have not controlled for potential individual-, familial-
and environmental-level confounders. AIM: To determine the association between
childhood maltreatment and lower sleep quality after adjusting for potential
confounders. METHODS: Data for the present study were obtained from a pre-birth
cohort study of 3778 young adults (52.6% female) of the Mater Hospital-University
of Queensland Study of Pregnancy follow up at a mean age of 20.6 years. The Mater
Hospital-University of Queensland Study of Pregnancy is a prospective Australian
pre-birth cohort study of mothers consecutively recruited during their first
obstetric clinic visit at Brisbane's Mater Hospital in 1981-1983. Participants
completed the Pittsburgh Sleep Quality Index at the 21-year follow up. We linked
this dataset to agency-recorded substantiated cases of childhood maltreatment. A
series of separate logistic regression models was used to test whether childhood
maltreatment predicted lower sleep quality after adjustment for selected
confounders. RESULTS: Substantiated physical abuse significantly predicted lower
sleep quality in males. Single and multiple forms of childhood maltreatment,
including age of maltreatment and number of substantiations, did not predict
lower sleep quality in either gender in both crude and adjusted models. Not being
married, living in a residential problem area, cigarette smoking and
internalising were significantly associated with lower sleep quality in a fully
adjusted model for the male-female combined sample. CONCLUSIONS: Childhood
maltreatment does not appear to predict young adult poor sleep quality, with the
exception of physical abuse for males. While childhood maltreatment has been
found to predict a range of mental health problems, childhood maltreatment does
not appear to predict sleep problems occurring in young adults. Poor sleep
quality was accounted for by concurrent social disadvantage, cigarette smoking
and internalising.
PMID- 28422455
TI - A decade of leafminer invasion in China: lessons learned.
AB - Liriomyza trifolii (Burgess) is a highly invasive species that has become
established in agricultural and ornamental crops throughout the world. L.
trifolii was first recorded in China in 2005 in Guangdong Province. Subsequently,
its known distribution in China has rapidly expanded to another 11 provinces
(Zhejiang, Jiangsu, Shanghai, Fujian, Guangxi, Shandong, Hainan, Hebei, Henan,
Hubei and Anhui), where it is currently causing considerable damage and economic
losses. Experimental research and field surveys have contributed to our
understanding of the ecology of L. trifolii and particularly the process of
invasion and its interactions with other established, exotic Liriomyza leafminer
species. A number of factors have contributed to the successful establishment of
L. trifolii and displacement of interspecific competitors. In China, L. trifolii
has become a particularly devastating pest in areas with intensive farming with
extensive monocultures and a reliance on insecticide use. Integrated pest
management incorporating judicious applications of insecticide combined with
biological and cultural controls is likely to provide the best long-term
management strategy for L. trifolii. We provide information regarding 10 years of
L. trifolii invasion in China and discuss areas of future research to enhance our
overall understanding of the biology and ecology of L. trifolii and to improve
management programmes for this widespread invasive insect pest. (c) 2017 Society
of Chemical Industry.
PMID- 28422456
TI - Variable phenotype in a novel mutation in PHOX2B.
AB - We evaluated a family with three siblings, two of whom ages 2 years and 19
months, had long segment colonic agangliosis and anisocoria. The mother also had
anisocoria. All three affected family members were mildly dysmorphic with a flat
facial profile, square appearance to the face, depressed nasal bridge, and
anteverted nares. Genetic testing identified a novel heterozygous mutation,
c.234C>G, resulting in a premature stop codon in exon 1 of the PHOX2B gene.
Screening for neural crest tumors was performed in the siblings and to date has
been negative. This family supports a strong association between non polyalanine
tract mutations, autonomic dysfunction, and Hirschsprung disease, but suggests
mutation outside of the polyalanine tract may not dictate severe phenotype with
significant respiratory compromise. A unique finding in this family is the
association of congenital heart disease in two of the affected patients. These
malformations may be a sporadic isolated finding or the result of environmental
factors or a modifying allele. Given the association between congenital heart
disease and aberrant neural crest cell development, however, findings are
suggestive that congenital heart disease may be a rare feature of PHOX2B mutation
which has not been previously reported.
PMID- 28422457
TI - Echoes of the Sarajevo Declaration on integrity and visibility of scholarly
publications.
PMID- 28422458
TI - Publication ethics standards should be the same for all peer-reviewed journals.
PMID- 28422459
TI - The Effect of Use of a Sonic Power Toothbrush and a Manual Toothbrush Control on
Plaque and Gingivitis.
AB - OBJECTIVES: To compare the ability of the Philips Sonicare DiamondClean power
toothbrush and the ADA Reference manual toothbrush to reduce plaque and gingival
inflammation by routine manual toothbrush users. METHODS: This was a randomized,
single-blind, parallel-design study. Eligible subjects were generally healthy non
smokers who exhibited mild to moderate gingivitis upon study entry. Enrolled
subjects were randomly allocated to commence twice-daily home use of either a
Philips Sonicare DiamondClean (DiamondClean) power toothbrush or an ADA reference
manual toothbrush (MTB) for a period of four weeks. Clinical safety and efficacy
were assessed after a two- and four-week period of home use. Statistical analysis
was performed for the modified intent to treat (mITT) population using a mixed
model with the Baseline score as a covariate. RESULTS: A total of 182 volunteers
were screened, 144 (72 per treatment) were randomized, and 142 subjects completed
this study. Following four weeks of use, the Least Square (LS) Mean SE) percent
reduction in surface plaque was 34.9% (1.8) for DiamondClean and 8.0% (1.7) for
MTB, (p < 0.0001). At the same four-week time point, the LS Mean (SE) percent
reduction in gingival inflammation for DiamondClean was 25.5% (1.9) and 19.1%
(1.9) for MTB (p = 0.0213). For gingival bleeding, the LS Mean (SE) percent
reduction in sites with gingival bleeding for DiamondClean was 57.4% (3.06) and
31.4% (3.04) for MTB (p < 0.0001). CONCLUSIONS: The Philips Sonicare DiamondClean
power toothbrush was statistically significantly more effective than a manual
toothbrush in reducing supragingival plaque, gingival inflammation, and gingival
bleeding following a four-week period of home use. Both products were safe for
home use.
PMID- 28422460
TI - An Evaluation of Plaque and Gingivitis Reduction Following Home Use of Sonicare
FlexCare Platinum with Premium Plaque Control Brush Head and a Manual Toothbrush.
AB - OBJECTIVES: To assess the effect of the Philips Sonicare FlexCare Platinum with
Premium plaque control brush head on gingival inflammation, bleeding, and
supragingival plaque reduction following a six-week period of home use compared
to a manual toothbrush. METHODS: This was a randomized, single-blind, parallel
design clinical trial. Subjects included in the study were routine manual
toothbrush users who were generally healthy non-smokers, aged 18-65 years, with
mild to moderate gingivitis. Subjects with advanced periodontal disease,
excessive gingival recession, and heavy deposits of calculus or rampant decay
were excluded from the study. Eligible participants were dispensed either Philips
Sonicare FlexCare Platinum with Premium plaque control brush head (PC), or an ADA
Reference manual toothbrush (MTB) for twice-daily home oral hygiene procedures
for six weeks. Efficacy measures included the Lobene and Soparker Modification of
Quigley and Hein Plaque Index (MPI), the Modified Gingival Index (MGI), and
Gingival Bleeding Index (GBI). Safety was evaluated by oral examination and
subject report. Efficacy and safety were assessed at Baseline, and at two and six
weeks following product home use. RESULTS: Of 154 subjects randomized, 143
subjects completed the study. For the primary endpoint, MGI at Week 2,
statistically significantly larger reductions in MGI were observed for PC versus
MTB, p < 0.0001. The adjusted mean reduction and standard error estimates (SE)
for MGI, expressed as percent reduction versus Baseline to Week 2, were 41.73%
(2.00%) for PC and 7.38% (2.02%) for MTB. Statistically significant differences
were also observed for MPI and GBI at Week 2, and for all metrics at Week 6.
CONCLUSIONS: Philips Sonicare FlexCare Platinum with Premium plaque control brush
head statistically significantly reduces gingival inflammation, gingival
bleeding, and plaque following two and six weeks of home use, compared to manual
tooth brushing alone.
PMID- 28422461
TI - The Effectiveness of Manual versus High-Frequency, High-Amplitude Sonic Powered
Toothbrushes for Oral Health: A Meta-Analysis.
AB - OBJECTIVES: Evaluate the short-term clinical efficacy of high-frequency, high
amplitude sonic powered toothbrushes compared to manual toothbrushes on plaque
removal and gingivitis reduction in everyday use through a meta-analysis of
randomized controlled trials. METHODS: Embase, MEDLINE, BIOSIS, Inspec, PQ
SciTech, Compendex, SciSearch and IADR abstracts databases were searched.
Eligible were clinical trials comparing at least one manual to one sonic powered
toothbrush on plaque or gingivitis reduction over four weeks to three months in
subjects without disability that could affect tooth brushing. Two authors
selected and extracted data from eligible studies. When insufficient information
was available, researchers were contacted. Data were pooled using random-effects
models to compute standardized mean differences (SMD) and 95% confidence
intervals (95% CI) quantifying differences in plaque or gingivitis reduction.
Risk for bias and sources of heterogeneity were assessed. RESULTS: The combined
results of 18 studies comprising 1,870 subjects showed that sonic powered
toothbrushes had statistically significantly greater plaque removal (SMD = -0.89,
95%CI = [-1.27, -0.51]) and gingivitis reduction (-0.67, [-1.01, -0.32]).
Heterogeneity was large and bias was not apparent. CONCLUSIONS: High-frequency,
high-amplitude sonic powered toothbrushes decreased plaque and gingivitis
significantly more effectively than manual toothbrushes in everyday use in
studies lasting up to three months.
PMID- 28422462
TI - A Comparison of the Effect of Two Power Toothbrushes on the Gingival Health and
Plaque Status of Subjects with Moderate Gingivitis.
AB - OBJECTIVES: To compare the effect of the Philips Sonicare DiamondClean plus
Premium plaque control brush head with the Oral-B 7000 plus CrossAction brush
head on gingivitis and supragingival plaque reduction following a 42-day period
of home use. METHODS: This was a randomized, parallel, examiner-blind,
prospective clinical trial conducted on generally healthy subjects. Eligible
subjects met the following eligibility criteria: age 18-65, non-smoker, routine
manual toothbrush user, >= 50 sites of gingival bleeding per the Gingival
Bleeding Index (GBI), and >= 1.8 plaque score per the Modified Plaque Index
(MPI), assessed three to six hours following the last oral hygiene procedure.
Eligible subjects were enrolled in the study and randomly assigned to use either
a Philips Sonicare DiamondClean with Premium plaque control brush head power
toothbrush (SPC) or an Oral-B(r) 7000 with CrossActionTM brush head power
toothbrush (OCA), for twice daily home use over a period of 42 days. All subjects
were dispensed a standard fluoride-containing dentifrice and both toothbrushes
were to be used in their respective Deep Clean modes. Safety and efficacy
evaluations were performed at 14 and 42 days following Baseline. RESULTS: Two
hundred eighty-four subjects completed this trial (142 subjects per treatment
group). Least squares mean (95% CI) estimates for reduction and percent reduction
of gingivitis per Modified Gingival Index (MGI) following 42 days of product use
for the SPC group were 1.17 (1.10, 1.24) and 45.68% (42.95%, 48.40%); for the OCA
group they were 0.69 (0.62, 0.76) and 26.83% (24.10%, 29.56%). The mean
difference (95% CI) between the two treatment groups was 0.48 (0.38, 0.58) and
18.85% (14.99%, 22.70%) for reduction and percent reduction, respectively. The
lower limit of the 95% CI for the difference in Overall score between the two
treatment groups was greater than the predefined non-inferiority margin (i.e.,
0.10 or -5%); therefore SPC was declared non-inferior to OCA. In addition, since
the 95% CI for the difference did not include zero, SPC was declared superior to
OCA in the reduction of gingivitis per MGI at Day 42 (p-value < 0.0001).
Similarly, for MGI at Day 14 and for GBI and MPI at Day 14 and Day 42,
significantly larger reductions were observed for SPC compared to OCA (p-value <
0.0001). CONCLUSIONS: Philips Sonicare DiamondClean with Premium plaque control
brush head (SPC) was statistically superior to the Oral-B 7000 with CrossAction
brush head (OCA) in reducing gingival inflammation, gingival bleeding, and
supragingival plaque following 14 and 42 days of home use. Both products were
safe for use.
PMID- 28422463
TI - Gingival Health and Plaque Regrowth Response Following a Four-Week Interdental
Hygiene Intervention.
AB - OBJECTIVES: To compare the efficacy of three adjunct interproximal cleaning
methods versus a manual toothbrush alone on gingivitis, and demonstrate that the
Philips Sonicare AirflossProTM interproximal (IP) cleaning device provides a
similar reduction in gingivitis and plaque compared to string floss. METHODS: A
randomized, single-blind, parallel-design study was conducted on generally
healthy adults exhibiting mild to moderate gingivitis. Eligible subjects were non
smokers, aged 18-65 years, with >= 0.5 per the Rustogi Modified Navy Plaque Index
(RMNPI) and a Gingival Bleeding Index (GBI) of >= 1 on at least 10 sites.
Eligible subjects were randomly assigned to use one of four oral hygiene
regimens: manual toothbrush (MTB) alone; MTB plus string floss (SF); MTB plus
Philips Sonicare AirflossPro used with Cool Mint Listerine(r) Antiseptic (AFPL);
and MTB plus Philips Sonicare AirflossPro used with BreathRxTM (AFPB). Subjects
were followed over a 28-day home-use period, with follow-up visits for efficacy
and safety conducted at Days 14 and 28. All subjects were instructed to use the
MTB twice daily and perform interproximal cleaning once daily, if assigned. Study
efficacy endpoints included the Modified Gingival Index (MGI), Rustogi Modified
Navy Plaque Index, and the Gingival Bleeding Index. RESULTS: Of 290 randomized
subjects, 287 were followed to Day 14 and 286 were followed to Day 28. For the
primary endpoint at Day 14, significantly larger reductions in MGI were observed
in each of the three IP cleaning groups compared to MTB alone (p < 0.001). The
adjusted mean reductions and standard error estimates (SE) for MGI expressed as a
percent reduction from Baseline at Day 14 were: 0.22% (0.55%) for MTB; 4.30%
(0.44%) for SF; 4.55% (0.45%) for AFPL; and 4.20% (0.44%) for AFPB. A non
inferiority test comparing AirflossPro to SF showed AirflossPro to be non
inferior to SF (p < 0.001). CONCLUSIONS: The addition of interproximal cleaning
to manual tooth brushing statistically significantly reduces gingivitis and
plaque compared to manual tooth brushing alone. Among the adjunct interproximal
cleaning regimens, AirflossPro provides a similar reduction in gingivitis and
plaque to string floss. All study regimens were safe on oral tissues.
PMID- 28422470
TI - Corrigendum.
PMID- 28422471
TI - [Epidemiological surveillance for multidrug-resistant microorganisms in a general
ICU].
AB - OBJECTIVE: Multidrug resistant (MDR) microorganisms represent a threat for
patients admitted in Intensive Care Units (ICUs). The objective of the present
study is to analyse the results of epidemiological surveillance cultures for
these microorganisms in one of these units. METHODS: General ICU. Retrospective
analysis, descriptive statistics. Analysis of epidemiological surveillance
cultures for MDR microorganisms in 2015. Studied microorganisms: Methicillin
resistant Staphylococcus aureus (MRSA), ESBL-and/or carbapenemase-producing
Klebsiella pneumoniae (CESBL-KP) and MDR Acinetobacter baumannii (MDRAB).
RESULTS: One thousand, two hundred and fifty nine patients admitted. A total of
2,234 specimens from 384 patients were analysed (690, 634, 62 and 286 were
rectal, throat, nasal and skin swabs respectively). Global APACHE II was 18.3 +/-
8 versus 21.7 +/- 7.8 in patients colonized/infected on admission. Global
mortality was 19.7% versus 22.3% in patients colonized/infected on admission. The
higher sensitivities achieved with the different samples for the different
microorganism detection were as follows. MRSA: 79% and 90% for nasal and nasal +
throat swabs, respectively. MDRAB: 80% and 95% for throat and throat + rectal
swabs, respectively. CESBL-KP: 95% and 98% for rectal and rectal + throat swabs,
respectively. 94 out of the 384 patients (24.4%) were colonized/infected with MDR
at admission. 134 patients (10.6% of the total patients admitted) were
colonized/infected with a total of 169 MMR during the hospital stay. MRSA has the
earliest colonization/infection (9.2 +/- 6.4days) and ESBL-producing
Enterobacteriaceae, the latest (18.7+/- 16.4 days). CONCLUSIONS: 24.4% of
patients were colonized/infected by MDR at admission. Nasal, throat and rectal
swabs were the most effective specimens for recovering MRSA, MDRAB and CESBL-KP,
respectively. The combination of two specimens improves MDR detection except for
CESBL-KP. Skin swabs are worthless. The most prevalent MDR at admission were ESBL
producing Enterobacteriaceae while the most frequent hospital acquired MDR was
MDRAB..
PMID- 28422472
TI - [Post-vaccination varicella in a patient receiving methotrexate].
PMID- 28422473
TI - [Flu in paediatrics: questions and possibilities].
PMID- 28422474
TI - [Comparison of two pattern for Streptococcus agalactiae screening using Granada
media].
PMID- 28422475
TI - [The significance of identification of Streptococcus agalactiae in urine cultures
for detection of Group B streptococcal colonization in pregnant women].
PMID- 28422476
TI - Origin-Dependent Variations in the Atmospheric Microbiome Community in Eastern
Mediterranean Dust Storms.
AB - Microorganisms carried by dust storms are transported through the atmosphere and
may affect human health and the functionality of microbial communities in various
environments. Characterizing the dust-borne microbiome in dust storms of
different origins or that followed different trajectories provides valuable data
to improve our understanding of global health and environmental impacts. We
present a comparative study on the diversity of dust-borne bacterial communities
in dust storms from three distinct origins (North Africa, Syria and Saudi Arabia)
and compare them with local bacterial communities sampled on clear days, all
collected at a single location: Rehovot, Israel. Storms from different dust
origins exhibited distinct bacterial communities, with signature bacterial taxa.
Dust storms were characterized by a lower abundance of selected antibiotic
resistance genes (ARGs) compared with ambient dust, asserting that the origin of
these genes is local and possibly anthropogenic. With the progression of the
storm, the storm-borne bacterial community showed increasing resemblance to
ambient dust, suggesting mixing with local dust. These results show, for the
first time, that dust storms from different sources display distinct bacterial
communities, suggesting possible diverse effects on the environment and public
health.
PMID- 28422477
TI - Core-Shell NiFe-LDH@NiFe-Bi Nanoarray: In Situ Electrochemical Surface Derivation
Preparation toward Efficient Water Oxidation Electrocatalysis in near-Neutral
Media.
AB - The corrosion issue with acidic and alkaline water electrolyzers can be avoided
by developing water oxidation catalysts performing efficiently under benign
conditions. In this Letter, we report that a NiFe-borate layer can be generated
on a NiFe-layered double hydroxide nanosheet array hydrothermally grown on carbon
cloth via an in situ electrochemical surface derivation process in potassium
borate (K-Bi) solution. The resulting 3D NiFe-LDH@NiFe-Bi nanoarray (NiFe
LDH@NiFe-Bi/CC) demonstrates high activity for water oxidation, demanding
overpotentials of 444 and 363 mV to achieve 10 mA cm-2 in 0.1 and 0.5 M K-Bi (pH:
9.2), respectively, rivaling the performances of most reported non-noble-metal
catalysts in near-neutral media. Notably, this electrode also shows strong
electrochemical durability with a high turnover frequency of 0.54 mol O2 s-1 at
overpotential of 600 mV. All these features promise its use as an efficient earth
abundant catalyst material for water oxidation under eco-friendly conditions.
PMID- 28422478
TI - Reduction of Ammineruthenium(III) by Sulfide Enables In Vivo Electrochemical
Monitoring of Free Endogenous Hydrogen Sulfide.
AB - The discovery of endogenous sulfide in mammalian brain opens up a door to
understanding of the physiological function of hydrogen sulfide (H2S). The
transformation of different forms of sulfide (i.e., S2-, HS-, H2S, bound sulfane
sulfur, et al.) in various physiological conditions hurdles the direct detection
of hydrogen sulfide in vivo. Here, we find that ammineruthenium(III) (Ru(NH3)63+)
can catalyze the electrochemical oxidation of free sulfide including HS- and H2S
in a neutral solution (pH 7.4). This property is used to constitute an
electrochemical mechanism for selective detection of hydrogen sulfide. By
coupling in vivo microdialysis with selective electrochemical detection, we
successfully developed an integrated microchip-based online electrochemical
system (OECS) for continuous monitoring of free endogenous hydrogen sulfide in
the central nervous system (CNS). The microchip-based OECS is well responsive
toward hydrogen sulfide with high stability, sensitivity and selectivity.
Compared with the existing methods, the OECS does not require offline treatment
of brain tissue or adjustment of the detection solutions into acidic or strong
basic atmosphere. These priorities essentially enable the system to accurately
and reliably track dynamics of hydrogen sulfide in the CNS.
PMID- 28422479
TI - On-Demand Gas-to-Liquid Process To Fabricate Thermoresponsive Antimicrobial
Nanocomposites and Coatings.
AB - Antimicrobial material is emerging as a major component of the mitigation
strategy against microbial growth on abiotic surfaces. In this work, a newly
designed process is proposed to fabricate thermoresponsive antimicrobial
nanocomposites (TANs) and coatings (TACs) as an on-demand system.
Thermoresponsive polymer (TRP)-incorporated silver (Ag) nanocomposites with
silica nanoparticles (SNPs) or carbon nanotubes (CNTs; Ag-SNP@TRP or Ag-CNT@TRP)
were produced by a single-pass gas-to-liquid process. The SNPs or CNTs were first
produced by spark ablation and successively injected for dispersal in a liquid
cell containing polydimethylsiloxane, poly(N-isopropylacrylamide), and silver
nitrate under ultrasound irradiation. Suspensions of Ag-SNP@TRP or Ag-CNT@TRP
nanocomposites were then deposited on a touch screen panel (TSP) protection film
via electrohydrodynamic spray to form transparent antibacterial coatings.
Fundamental antibacterial activities of TANs were evaluated against Escherichia
coli and Staphylococcus epidermidis. The TANs showed stronger antibacterial
activities at the higher temperature for all testing conditions. Lower minimum
inhibitory concentrations of Ag-SNP@TRP and Ag-CNT@TRP nanocomposites were
required against the two bacteria at 37 degrees C compared to those at 27
degrees C. The TACs on display showed elevated antimicrobial activity when the
panel was turned on (38.1 degrees C) compared with when the panel was turned off
(23.8 degrees C). This work provides a utilizable concept to continuously
fabricate TANs and TACs, and it specifically offers stimuli-sensitive control of
antimicrobial activity on TSPs, including other frequently touched surfaces.
PMID- 28422480
TI - Chemical Characterization of Gas- and Particle-Phase Products from the Ozonolysis
of alpha-Pinene in the Presence of Dimethylamine.
AB - Amines are recognized as key compounds in new particle formation (NPF) and
secondary organic aerosol (SOA) formation. In addition, ozonolysis of alpha
pinene contributes substantially to the formation of biogenic SOAs in the
atmosphere. In the present study, ozonolysis of alpha-pinene in the presence of
dimethylamine (DMA) was investigated in a flow tube reactor. Effects of amines on
SOA formation and chemical composition were examined. Enhancement of NPF and SOA
formation was observed in the presence of DMA. Chemical characterization of gas-
and particle-phase products by high-resolution mass spectrometric techniques
revealed the formation of nitrogen containing compounds. Reactions between
ozonolysis reaction products of alpha-pinene, such as pinonaldehyde or pinonic
acid, and DMA were observed. Possible reaction pathways are suggested for the
formation of the reaction products. Some of the compounds identified in the
laboratory study were also observed in aerosol samples (PM1) collected at the
SMEAR II station (Hyytiala, Finland) suggesting that DMA might affect the
ozonolysis of alpha-pinene in ambient conditions.
PMID- 28422481
TI - Gold Nanoparticles Induced Endothelial Leakiness Depends on Particle Size and
Endothelial Cell Origin.
AB - The endothelium presents a formidable barrier for cancer nanomedicine, as the
intravenously introduced nanomedicine needs to leave the blood vessel at the
tumor site. Endothelial permeability and retention effect (EPR) is not dependable
since it is derived from tumors. Certain nanoparticles with specific
characteristics are able to induce micrometer sized gaps between endothelial
cells. This effect is called "nanoparticle induced endothelial leakiness"
(NanoEL). NanoEL therefore allows the nanotechnology to control access to the
tumor even in the absence of any EPR effect. Morever, NanoEL can be applicable to
noncancer issues, thereby expanding its usefulness in other subfields of
nanomedicine. In this paper, we have shown that Gold (Au) nanoparticles within
the range of 10-30 nm are good NanoEL inducing particles. As not all endothelial
cells have the same permeability, we found that human mammary endothelial cells
and human skin endothelial cells are sensitive to Au induced NanoEL, while human
umbilical vein endothelial cells are insensitive, reflective of their innate
nature of endothelial permeability. The size window and endothelial cell type
sensitivity then helps the nanotechnologists to design future nanoparticles that
either exploit NanoEL as a nanotechnology driven strategy to access immature
tumors, which do not induce the EPR effect, or avoid NanoEL as a nanotoxic side
effect.
PMID- 28422482
TI - Organosilica Nanoparticles with an Intrinsic Secondary Amine: An Efficient and
Reusable Adsorbent for Dyes.
AB - Nanomaterials are promising tools in water remediation because of their large
surface area and unique properties compared to bulky materials. We synthesized an
organosilica nanoparticle (OSNP) and tuned its composition for anionic dye
removal. The adsorption mechanisms are electrostatic attraction and hydrogen
bonding between the amine on OSNP and the dye, and the surface charge of the OSNP
can be tuned to adsorb either anionic or cationic dyes. Using phenol red as a
model dye, we studied the effect of the amine group, pH, ionic strength, time,
dye concentration, and nanomaterial mass on the adsorption. The theoretical
maximum adsorption capacity was calculated to be 175.44 mg/g (0.47 mmol/g), which
is higher than 67 out of 77 reported adsorbents. The experimental maximum
adsorption capacity is around 201 mg/g (0.53 mmol/g). Furthermore, the
nanoparticles are highly reusable and show stable dye removal and recovery
efficiency over at least 10 cycles. In summary, the novel adsorbent system
derived from the intrinsic amine group within the frame of OSNP are reusable and
tunable for anionic or cationic dyes with high adsorption capacity and fast
adsorption. These materials may also have utility in drug delivery or as a
carrier for imaging agents.
PMID- 28422483
TI - Transparent Flexible Multifunctional Nanostructured Architectures for Non-optical
Readout, Proximity, and Pressure Sensing.
AB - Electronic skins need to be versatile and able to detect multiple inputs beyond
simple pressure and touch while having attributes of transparency and facile
manufacturability. Herein, we demonstrate a versatile nanostructured transparent
sensor capable of detecting wide range of pressures and proximity as well as
novel nonoptical detection of printed patterns. The architecture and fabrication
processes are straightforward and show robustness to repeated cycling and
testing. The sensor displays good sensitivity and stability from 30 Pa to 5 kPa
without the use of microstructuration and is conformal and sensitive to be
utilized as a wrist-based heart-rate monitor. Highly sensitive proximity
detection is shown from a distance of 9 cm. Finally, a unique nonoptical pattern
recognition dependent on the difference in the dielectric constant between ink
and paper is also demonstrated, indicating the multifunctionality of this simple
architecture.
PMID- 28422484
TI - Direct Synthesis of Dextran-Based Antibacterial Hydrogels for Extended Release of
Biocides and Eradication of Topical Biofilms.
AB - Cationic small molecular biocides have been developed as promising antibiofilm
agents because of their tunability in chemical structures and their ability to
disrupt established biofilms. However, the impact of biocides in antibiofilm
treatment is largely limited due to the lack of an effective delivery system that
can ensure sustained release of biocides at the target site. Herein we report a
biocide-encapsulated antibacterial and antibiofilm hydrogel that acts as an
efficient delivery vehicle for the biocide and eradicates matured bacterial
biofilm. The hydrogels are prepared using dextran methacrylate (Dex-MA), a
biocompatible and photopolymerizable polymer, and a nontoxic cationic biocide
with two cationic charges, two nonpeptidic amide bonds, and optimized
amphiphilicity, which is capable of eradicating established bacterial biofilms.
The gels, prepared via direct loading of the biocide and with highly controllable
amounts, display 100% activity against both drug-sensitive and drug-resistant
bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Importantly,
the gels are shown to release the biocide and kill bacteria for an extended
period of time (until day 5). When being treated with the established bacterial
biofilms, the released biocide from the gel is shown to completely eradicate
establishedS. aureus, Escherichia coli, and MRSA biofilms, the most common
biofilm forming bacteria that cause severe infections (e.g., skin infections,
urinary tract infections, etc.) in humans. Moreover, the gels were shown to
annihilate preformed MRSA biofilm with >99.99% bacterial reduction under in vitro
and in vivo conditions in a superficial MRSA infection model in mice. Notably,
when tested, excellent skin compatibility is observed for these materials in
various animal models such as a rat model of acute dermal toxicity, guinea pig
model of skin sensitization, and rabbit model of skin irritation. The
biocompatible antibacterial and antibiofilm hydrogels developed herein thus might
be useful in treating bacterial biofilm associated infections, especially topical
infections.
PMID- 28422485
TI - Fabrication of a Highly Sensitive Single Aligned TiO2 and Gold Nanoparticle
Embedded TiO2 Nano-Fiber Gas Sensor.
AB - In this research, a single-aligned nanofiber of pure TiO2 and gold nanoparticle
(GNP)-TiO2 were fabricated using a novel electro-spinning procedure equipped with
secondary electrostatic fields on highly sharp triangular and rectangular
electrodes provided for gas sensing applications. The sol used for spinning
nanofiber consisted of titanium tetraisopropoxide (C12H28O4Ti), acetic acid
(CH3COOH), ethanol (C2H5OH), polyvinylpyrrolidone (PVP), and gold nanoparticle
solution. FE-SEM, TEM, and XRD were used to characterize the single nanofiber. In
triangular electrodes, the electrostatic voltage for aligning single nanofiber
between electrodes depends on the angle tip of the electrode, which was around
1.4-2.1, 2-2.9, and 3.2-4.1 kV for 30 degrees , 45 degrees , and 60 degrees ,
respectively. However, by changing the shape of the electrodes to rectangular
samples and by increasing distance between electrodes from 100 to 200 MUm,
electro-spinning applied voltage decreased. Response of pure TiO2 single
nanofiber sensor was measured for 30-200 ppb carbon monoxide gas. The triangular
sample revealed better response and lower threshold than the rectangular sample.
Adding appropriate amounts of GNP decreased the operating temperature and
increased the responses. CO concentration threshold for the pure TiO2 and GNP
TiO2 triangular samples was about 5 ppb and 700 ppt, respectively.
PMID- 28422486
TI - Stable Nanocomposite Based on PEGylated and Silver Nanoparticles Loaded Graphene
Oxide for Long-Term Antibacterial Activity.
AB - The increasing occurrence of antibiotic-resistant pathogens, especially
superbugs, is compromising the efficacy of traditional antibiotics. Silver
nanoparticles (AgNPs) loaded graphene oxide (GO) nanocomposite (GO-Ag) has drawn
great interest as a promising alternative antibacterial material. However, GO-Ag
nanocomposite often irreversibly aggregates in physiological solutions, severely
influencing its antibacterial capacity and practical application. Herein, a
PEGylated and AgNPs loaded GO nanocomposite (GO-PEG-Ag) is synthesized through a
facile approach utilizing microwave irradiation, while avoiding extra reducing
agents. Through PEGylation, the synthesized GO-PEG-Ag nanocomposite dispersed
stably over one month in a series of media and resisted centrifugation at 10
000*g for 5 min, which would benefit effective contact between the nanocomposite
and the bacteria. In contrast, GO-Ag aggregated within 1 h of dispersion in
physiological solutions. In comparison with GO-Ag, GO-PEG-Ag showed stronger
bactericidal capability toward not only normal Gram-negative/positive bacteria
such as E. coli and S. aureus (~100% of E. coli and ~95.3% of S. aureus reduction
by 10 MUg/mL nanocomposite for 2.5 h), but also superbugs. Moreover, GO-PEG-Ag
showed lower cytotoxicity toward HeLa cells. Importantly, GO-PEG-Ag presented
long-term antibacterial effectiveness, remaining ~95% antibacterial activity
after one-week storage in saline solution versus <35% for GO-Ag. The
antibacterial mechanisms of GO-PEG-Ag were evidenced as damage to the bacterial
structure and production of reactive oxygen species, causing cytoplasm leakage
and metabolism decrease. The stable GO-PEG-Ag nanocomposite with powerful and
long-term antibacterial capability provides a more practical and effective
strategy for fighting superbugs-including pathogen threats in biomedicine and
public health.
PMID- 28422487
TI - Stepwise Deoxygenation of Nitrite as a Route to Two Families of Ruthenium
Corroles: Group 8 Periodic Trends and Relativistic Effects.
AB - Given the many applications of ruthenium porphyrins, the rarity of ruthenium
corroles and the underdeveloped state of their chemistry are clearly indicative
of an area ripe for significant breakthroughs. The tendency of ruthenium corroles
to form unreactive metal-metal-bonded dimers has been recognized as a key
impediment in this area. Herein, by exposing free-base meso-tris(p-X
phenyl)corroles, H3[TpXPC] (X = CF3, H, Me, and OMe), and [Ru(COD)Cl2]x in
refluxing 2-methoxyethanol to nitrite, we have been able to reliably intercept
the series Ru[TpXPC](NO) in a matter of seconds to minutes and subsequently
RuVI[TpXPC](N), the products of a second deoxygenation, over some 16 h. Two of
the RuVIN complexes and one ruthenium corrole dimer could be crystallographically
analyzed; the Ru-Nnitrido distance was found to be ~1.61 A, consistent with the
triple-bonded character of the RuVIN units and essentially identical with the Os
Nnitrido distance in analogous osmium corroles. Spectroscopic and density
functional theory (DFT) calculations suggest that the RuNO corroles are best
viewed as innocent {RuNO}6 complexes, whereas the analogous FeNO corroles are
noninnocent, i.e., best viewed as {FeNO}7-corrole*2-. Both RuVIN and OsVIN
corroles exhibit sharp Soret bands, suggestive of an innocent macrocycle. A key
difference between the two metals is that the Soret maxima of the OsVIN corroles
are red-shifted some 25 nm relative to those of the RuVIN complexes. Careful time
dependent DFT studies indicate that this difference is largely attributable to
relativistic effects in OsVIN corroles. The availability of two new classes of
mononuclear ruthenium corroles potentially opens the door to new applications, in
such areas as catalysis and cancer therapy.
PMID- 28422488
TI - Pressure-Driven Isostructural Phase Transition in InNbO4: In Situ Experimental
and Theoretical Investigations.
AB - The high-pressure behavior of technologically important visible-light
photocatalytic semiconductor InNbO4, adopting a monoclinic wolframite-type
structure at ambient conditions, was investigated using synchrotron-based X-ray
diffraction, Raman spectroscopic measurements, and first-principles calculations.
The experimental results indicate the occurrence of a pressure-induced
isostructural phase transition in the studied compound beyond 10.8 GPa. The large
volume collapse associated with the phase transition and the coexistence of two
phases observed over a wide range of pressure shows the nature of transition to
be first-order. There is an increase in the oxygen anion coordination number
around In and Nb cations from six to eight at the phase transition. The ambient
pressure phase has been recovered on pressure release. The experimental pressure
volume data when fitted to a Birch-Murnaghan equation of states yields the value
of ambient pressure bulk modulus as 179(2) and 231(4) GPa for the low- and high
pressure phases, respectively. The pressure dependence of the Raman mode
frequencies and Gruneisen parameters was determined for both phases by
experimental and theoretical methods. The same information is obtained for the
infrared modes from first-principles calculations. Results from theoretical
calculations corroborate the experimental findings. They also provide information
on the compressibility of interatomic bonds, which is correlated with the
macroscopic properties of InNbO4.
PMID- 28422489
TI - Generalized Switch Functions in the Multilevel Many-Body Expansion Method and Its
Application to Water Clusters.
AB - The many-body expansion (MBE) method is the basis of many fragment-based methods
and is widely applied to the computation of large molecular systems. To reach
linear-scaling computation, a cutoff must be used to discard those subsystems
with long interfragment distances. However, this leads to a discontinuous
potential energy surface (PES) that would cause various problems in geometry
optimizations and molecular dynamics simulations. To solve this problem, we
present a generalized-switch-function (GSF) approach to smooth the PES computed
by the MBE method with the use of a cutoff distance. The GSFs are naturally
normalized and are permutation invariant. This approach can be applied to
adaptively computing any order of many-body correction energies with multilevel
computational methods and is a dynamic subsystem approach. We have applied the
two versions of our method, GSF-MBE(m)/L1 and GSF-MBE(m)/(L1:L2:L3), to water
clusters. Thorough tests show that our method can indeed give smooth potential
energy surface and is linear scaling but without losing much accuracy for very
large water clusters with appropriately chosen cutoff distances.
PMID- 28422490
TI - Redox-Tagged Carbon Monoxide-Releasing Molecules (CORMs): Ferrocene-Containing
[Mn(C^N)(CO)4] Complexes as a Promising New CORM Class.
AB - This study describes the synthesis and characterization of a new class of
ferrocene-containing carbon monoxide-releasing molecules (CORMs, 1-3). The
ferrocenyl group is both a recognized therapeutically viable coligand and a
handle for informative infrared spectroelectrochemistry. Deoxymyoglobin CO
release assays and in situ infrared spectroscopy confirm compounds 2 and 3 as
photoCORMs and 1 as a thermal CORM, attributed to the increased sensitivity of
the Mn-ferrocenyl bond to protonation in 1. Electrochemical and infrared
spectroelectrochemical experiments confirm a single reversible redox couple
associated with the ferrocenyl moiety with the Mn tetracarbonyl center showing no
redox activity up to +590 mV vs Fc/Fc+, though no concomitant CO release was
observed in association with the redox activity. The effects of linker length on
communication between the Fe and Mn centers suggest that the incorporation of
redox-active ligands into CORMs focuses on the first coordination sphere of the
CORM. Redox-tagged CORMs could prove to be a useful mechanistic probe; our
findings could be developed to use redox changes to trigger CO release.
PMID- 28422491
TI - Discovery of Novel Ligands for TNF-alpha and TNF Receptor-1 through Structure
Based Virtual Screening and Biological Assay.
AB - Tumor necrosis factor alpha (TNF-alpha) is overexpressed in various diseases, and
it has been a validated therapeutic target for autoimmune diseases. All
therapeutics currently used to target TNF-alpha are biomacromolecules, and
limited numbers of TNF-alpha chemical inhibitors have been reported, which makes
the identification of small-molecule alternatives an urgent need. Recent studies
have mainly focused on identifying small molecules that directly bind to TNF
alpha or TNF receptor-1 (TNFR1), inhibit the interaction between TNF-alpha and
TNFR1, and/or regulate related signaling pathways. In this study, we combined in
silico methods with biophysical and cell-based assays to identify novel
antagonists that bind to TNF-alpha or TNFR1. Pharmacophore model filtering and
molecular docking were applied to identify potential TNF-alpha antagonists. In
regard to TNFR1, we constructed a three-dimensional model of the TNF-alpha-TNFR1
complex and carried out molecular dynamics simulations to sample the
conformations. The residues in TNF-alpha that have been reported to play
important roles in the TNF-alpha-TNFR1 complex were removed to form a pocket for
further virtual screening of TNFR1-binding ligands. We obtained 20 virtual hits
and tested them using surface plasmon resonance-based assays, which resulted in
one ligand that binds to TNFR1 and four ligands with different scaffolds that
bind to TNF-alpha. T1 and R1, the two most active compounds with Kd values of 11
and 16 MUM for TNF-alpha and TNFR1, respectively, showed activities similar to
those of known antagonists. Further cell-based assays also demonstrated that T1
and R1 have similar activities compared to the known TNF-alpha antagonist C87.
Our work has not only produced several TNF-alpha and TNFR1 antagonists with novel
scaffolds for further structural optimization but also showcases the power of our
in silico methods for TNF-alpha- and TNFR1-based drug discovery.
PMID- 28422492
TI - A Concise, Efficient and Scalable Total Synthesis of Thapsigargin and
Nortrilobolide from (R)-(-)-Carvone.
AB - A concise, efficient and scalable synthesis of thapsigargin and nortrilobolide
from commercially available (R)-(-)-carvone was developed. Our synthetic strategy
is inspired by nature's carbon-carbon bond formation sequence, which facilitates
the construction of a highly functionalized sesquiterpene lactone skeleton in
five steps via an enantioselective ketone alkylation and a diastereoselective
pinacol cyclization. We envision that this strategy will permit the construction
of other members of the family, structural analogs and provide a practical
synthetic route to these important bioactive agents. In addition, we anticipate
that the prodrug Mipsagargin, which is currently in late-stage clinical trials
for the treatment of cancer, will also be accessible via this strategy. Hence,
the limited availability from natural sources, coupled with an estimated demand
of one metric ton per annum for the prodrug, provides a compelling mandate to
develop practical total syntheses of these agents.
PMID- 28422493
TI - Triazolide Strigolactone Mimics Influence Root Development in Arabidopsis.
AB - Strigolactones are the most recently recognized class of phytohormones, which are
also known to establish plant symbiosis with arbuscular mycorhizal fungi or
induce germination of parasitic plants. Their relatively complex structures and
low stability urgently calls for simple derivatives with maintained biological
function. We have prepared a series of triazolide strigolactone mimics and
studied their ability to affect root development of Arabidopsis thaliana. The
strigolactone mimics significantly induced root elongation and lateral root
formation while resembling the effect of the reference compound GR24.
PMID- 28422494
TI - Genetically Encoded 2-Aryl-5-carboxytetrazoles for Site-Selective Protein Photo
Cross-Linking.
AB - The genetically encoded photo-cross-linkers promise to offer a temporally
controlled tool to map transient and dynamic protein-protein interaction
complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5
carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation
into proteins via amber codon suppression in Escherichia coli and mammalian
cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was
found to give robust and site-selective photo-cross-linking reactivity in E. coli
when placed at an appropriate site at the protein interaction interface. A
comparison study indicated that mPyTK exhibits higher photo-cross-linking
efficiency than a diazirine-based photo-cross-linker, AbK, when placed at the
same location of the interaction interface in vitro. When mPyTK was introduced
into the adapter protein Grb2, it enabled the photocapture of EGFR in a stimulus
dependent manner. The design of mPyTK along with the identification of its
cognate aminoacyl-tRNA synthetase makes it possible to map transient protein
protein interactions and their interfaces in living cells.
PMID- 28422495
TI - Cochliotoxin, a Dihydropyranopyran-4,5-dione, and Its Analogues Produced by
Cochliobolus australiensis Display Phytotoxic Activity against Buffelgrass
(Cenchrus ciliaris).
AB - Buffelgrass (Pennisetum ciliare or Cenchrus ciliaris) is a perennial grass that
has become highly invasive in the Sonoran Desert of southern Arizona. In the
search for novel control strategies against this weed, strains of the foliar
fungal pathogen Cochliobolus australiensis from buffelgrass have been screened
for their ability to produce phytotoxic metabolites that could potentially be
used as natural herbicides in an integrated pest management strategy. A new
phytotoxin, named cochliotoxin, was isolated from liquid culture of this fungus
together with radicinin, radicinol, and their 3-epimers. Cochliotoxin was
characterized, essentially by spectroscopic methods, as 3-hydroxy-2-methyl-7-(3
methyloxiranyl)-2,3-dihydropyrano[4,3-b]pyran-4,5-dione. Its relative
stereochemistry was assigned by 1H NMR techniques, while the absolute
configuration (2S,3S) was determined applying the advanced Mosher's method by
esterification of its hydroxy group at C-3. When bioassayed in a buffelgrass
coleoptile elongation test and by leaf puncture bioassay against the host weed
and two nontarget grasses, cochliotoxin showed strong phytotoxicity. In the same
tests, radicinin and 3-epi-radicinin also showed phytotoxic activity, while
radicinol and 3-epi-radicinol were largely inactive. All five compounds were more
active in leaf puncture bioassays on buffelgrass than on the nontarget grass
tanglehead (Heteropogon contortus), while the nontarget grass Arizona cottontop
(Digitaria californica) was more sensitive to radicinin and 3-epi-radicinin.
Cochliotoxin at low concentration was significantly more active on buffelgrass
than on either native grass, but the difference was small.
PMID- 28422496
TI - The Combined Use of Proteomics and Transcriptomics Reveals a Complex Secondary
Metabolite Network in Peperomia obtusifolia.
AB - Peperomia obtusifolia, an ornamental plant from the Piperaceae family,
accumulates a series of secondary metabolites with interesting biological
properties. From a biosynthesis standpoint, this species produces several
benzopyrans derived from orsellinic acid, which is a polyketide typically found
in fungi. Additionally, the chiral benzopyrans were reported as racemic and/or as
diastereomeric mixtures, which raises questions about the level of enzymatic
control in the cyclization step for the formation of the 3,4-dihydro-2H-pyran
moiety. Therefore, this article describes the use of shotgun proteomic and
transcriptome studies as well as phytochemical profiling for the characterization
of the main biosynthesis pathways active in P. obtusifolia. This combined
approach resulted in the identification of a series of proteins involved in its
secondary metabolism, including tocopherol cyclase and prenyltransferases. The
activity of these enzymes was supported by the phytochemical profiling performed
in different organs of P. obtusifolia. However, the polyketide synthases possibly
involved in the production of orsellinic acid could not be identified, suggesting
that orsellinic acid may be produced by endophytes intimately associated with the
plant.
PMID- 28422497
TI - Mechanistic Study of Arylsilane Oxidation through 19F NMR Spectroscopy.
AB - The mechanism of the oxidation of arylsilanes to phenols has been investigated
using 19F NMR spectroscopy. The formation of silanols in these reactions results
from a rapid background equilibrium between silanol and alkoxysilane; the
relative rates of reaction of these species was evaluated by modeling of
concentration profiles obtained through 19F NMR spectroscopic reaction
monitoring. Combining these results with a study of initial rates of phenol
formation, and of substituent electronic effects, a mechanistic picture involving
rapid and reversible formation of a pentavalent peroxide ate complex, prior to
rate-limiting aryl migration, has evolved.
PMID- 28422498
TI - Selective Oxygenation of Cyclohexene by Dioxygen via an Iron(V)-Oxo Complex
Autocatalyzed Reaction.
AB - An iron complex with a tetraamido macrocyclic ligand, [(TAML)FeIII]-, was found
to be an efficient and selective catalyst for allylic oxidation of cyclohexene by
dioxygen (O2); cyclohex-2-enone was obtained as the major product along with
cyclohexene oxide as the minor product. An iron(V)-oxo complex, [(TAML)FeV(O)]-,
which was formed by activating O2 in the presence of cyclohexene, initiated the
autoxidation of cyclohexene with O2 to produce cyclohexenyl hydroperoxide, which
reacted with [(TAML)FeIII]- to produce [(TAML)FeV(O)]- by autocatalysis. Then,
[(TAML)FeV(O)]- reacted rapidly with [(TAML)FeIII]- to produce a MU-oxo dimer,
[(TAML)FeIV(O)FeIV(TAML)]2-, which was ultimately converted to [(TAML)FeV(O)]-
when [(TAML)FeIII]- was not present in the reaction solution. An induction period
was observed in the autocatalytic production of [(TAML)FeV(O)]-. The induction
period was shortened with increasing catalytic amounts of [(TAML)FeV(O)]- and
cyclohexenyl hydroperoxide, whereas the induction period was prolonged by adding
catalytic amounts of a spin trapping reagent such as 5,5-dimethyl-1-pyrroline N
oxide (DMPO). The allylic oxidation of cycloalkenes was also found to depend on
the allylic C-H bond dissociation energies, suggesting that the hydrogen atom
abstraction from the allylic C-H bonds of cycloalkenes is the rate-determining
radical chain initiation step. In this study, we have shown that an iron(III)
complex with a tetraamido macrocyclic ligand is an efficient catalyst for the
allylic oxidation of cyclohexene via an autocatalytic radical chain mechanism and
that [(TAML)FeV(O)]- acts as a reactive intermediate for the selective
oxygenation of cyclohexene with O2 to produce cyclohex-2-enone predominantly.
PMID- 28422499
TI - Development of a 18F-Labeled Radiotracer with Improved Brain Kinetics for
Positron Emission Tomography Imaging of Translocator Protein (18 kDa) in Ischemic
Brain and Glioma.
AB - We designed four novel acetamidobenzoxazolone compounds 7a-d as candidates for
positron emission tomography (PET) radiotracers for imaging the translocator
protein (18 kDa, TSPO) in ischemic brain and glioma. Among these compounds, 2-(5
(6-fluoropyridin-3-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide
(7d) exhibited high binding affinity (Ki = 13.4 nM) with the TSPO and moderate
lipophilicity (log D = 1.92). [18F]7d was radiosynthesized by [18F]fluorination
of the bromopyridine precursor 7h with [18F]F- in 12 +/- 5% radiochemical yield
(n = 6, decay-corrected). In vitro autoradiography and PET studies of ischemic
rat brain revealed higher binding of [18F]7d with TSPO on the ipsilateral side,
as compared to the contralateral side, and improved brain kinetics compared with
our previously developed radiotracers. Metabolite study of [18F]7d showed 93% of
unchanged form in the ischemic brain at 30 min after injection. Moreover, PET
study with [18F]7d provided a clear tumor image in a glioma-bearing rat model. We
demonstrated that [18F]7d is a useful PET radiotracer for visualizing not only
neuroinflammation but also glioma and will translate this radiotracer to a "first
in-human" study in our facility.
PMID- 28422500
TI - Influence of 13C Isotopic Labeling Location on Dynamic Nuclear Polarization of
Acetate.
AB - Dynamic nuclear polarization (DNP) via the dissolution method has alleviated the
insensitivity problem in liquid-state nuclear magnetic resonance (NMR)
spectroscopy by amplifying the signals by several thousand-fold. This NMR signal
amplification process emanates from the microwave-mediated transfer of high
electron spin alignment to the nuclear spins at high magnetic field and cryogenic
temperature. Since the interplay between the electrons and nuclei is crucial, the
chemical composition of a DNP sample such as the type of free radical used,
glassing solvents, or the nature of the target nuclei can significantly affect
the NMR signal enhancement levels that can be attained with DNP. Herein, we have
investigated the influence of 13C isotopic labeling location on the DNP of a
model 13C compound, sodium acetate, at 3.35 T and 1.4 K using the narrow electron
spin resonance (ESR) line width free radical trityl OX063. Our results show that
the carboxyl 13C spins yielded about twice the polarization produced in methyl
13C spins. Deuteration of the methyl 13C group, while proven beneficial in the
liquid-state, did not produce an improvement in the 13C polarization level at
cryogenic conditions. In fact, a slight reduction of the solid-state 13C
polarization was observed when 2H spins are present in the methyl group.
Furthermore, our data reveal that there is a close correlation between the solid
state 13C T1 relaxation times of these samples and the relative 13C polarization
levels. The overall results suggest the achievable solid-state polarization of
13C acetate is directly affected by the location of the 13C isotopic labeling via
the possible interplay of nuclear relaxation leakage factor and cross-talks
between nuclear Zeeman reservoirs in DNP.
PMID- 28422501
TI - Interfacial Activity of Nonamphiphilic Particles in Fluid-Fluid Interfaces.
AB - Surfactants can adsorb in fluid-fluid interfaces and lower the interfacial
tension. Like surfactants, particles with appropriate wettability can also adsorb
in fluid-fluid interfaces. Despite many studies of particle adsorption at fluid
interfaces, some confusion persists regarding the ability of (simple,
nonamphiphilic) particles to reduce the interfacial tension. In the present work,
the interfacial activity of silica nanoparticles at air-water and hexadecane
water interfaces and of ethyl cellulose particles at the interface of water with
trimethylolpropane trimethacrylate was analyzed through pendant drop tensiometry.
Our measurements strongly suggest that the particles do significantly affect the
interfacial tension provided that they have a strong affinity to the interface by
virtue of their wettability and that no energy barrier to adsorption prevents
them from reaching the interface. A simplistic model that does not explicitly
account for any particle-particle interactions is found to yield surprisingly
good predictions for the effective interfacial tension in the presence of the
adsorbed particles. We further propose that interfacial tension measurements,
when combined with information about the particles' wetting properties, can
provide a convenient way to estimate the packing density of particles in fluid
fluid interfaces. These results may help to understand and control the assembly
of nonamphiphilic nanoparticles at fluid-fluid interfaces, which is relevant to
applications ranging from surfactant-free formulations and food technology to oil
recovery.
PMID- 28422502
TI - Arrays of Ag and Au Nanoparticles with Terpyridine- and Thiophene-Based Ligands:
Morphology and Optical Responses.
AB - The assembly of Ag and Au nanoparticles (NPs) into nanoparticulate arrays
mediated by terpyridine (tpy), 4'-(2-thienyl)terpyridine (T-tpy), and short
alpha,omega-bis(tpy)oligothiophene ligands has been accomplished at the interface
between the Ag or Au NP hydrosol and a solution of the molecular species in
dichloromethane. The relationship between the morphology and the optical
responses of the arrays has been investigated by advanced methods of TEM
(transmission electron microscopy) image analysis and surface plasmon extinction
(SPE) spectra. It has been established that the size of islands of closely spaced
NPs rather than the average interparticle distance affects the extent of
delocalization of the surface plasmon excitations and thus also the SPE spectra.
Furthermore, the structure of surface-adsorbate complexes formed in these arrays
has been investigated by SERS spectral measurements carried out as a function of
the excitation wavelength. Photoinduced charge transfer (CT) transitions from the
neutral Ags0 and Aus0 adsorption sites on metal NPs to antibonding orbitals of
the adsorbates have been identified for Ag/tpy, Ag/T-tpy, Au/tpy, and Au/T-tpy
nanoparticulate arrays. Although the surface-adsorbate complexes displaying a
photoinduced CT are known for Ag NPs, the Aus0 surface complexes with this CT are
newly reported. Bis(tpy)oligothiophenes were found to be attached to both Ag and
Au NPs via the tpy group(s). The match between the interparticle distances within
the NP islands and the lengths of the oligomers molecules indicates that the
molecules act as interparticle linkers. In this case, unequivocal spectral marker
band evidence of the Ags0 as well as Aus0 surface complex formation has not been
obtained.
PMID- 28422503
TI - Predicting Protein Interactions of Concentrated Globular Protein Solutions Using
Colloidal Models.
AB - Protein interactions of alpha-chymotrypsinogen A (aCgn) were quantified using
light scattering from low to high protein concentrations. Static light scattering
(SLS) was used to determine the excess Rayleigh ratio (Rex) and osmotic second
virial coefficients (B22) as a function of pH and total ionic strength (TIS).
Repulsive (attractive) protein-protein interactions (PPI) were observed at pH 5
(pH 7), with decreasing repulsions (attractions) upon increasing TIS. Simple
colloidal potential of mean force models (PMF) that account for short-range
nonelectrostatic attractions and screened electrostatic interactions were used to
fit model parameters from data for B22 vs TIS at both pH values. The parameters
and PMF models from low-concentration conditions were used as the sole input to
transition matrix Monte Carlo simulations to predict high concentration Rex
behavior. At conditions where PPI are repulsive to slightly attractive,
experimental Rex data at high concentrations could be predicted quantitatively by
the simulations. However, accurate predictions were challenging when PPI were
strongly attractive due to strong sensitivity to changes in PMF parameter values.
Additional simulations with higher-resolution coarse-grained molecular models
suggest an approach to qualitatively predict cases when anisotropic surface
charge distributions will lead to overall attractive PPI at low ionic strength,
without assumptions regarding electrostatic "patches" or multipole expansions.
PMID- 28422505
TI - Probing Homogeneous Line Broadening in CdSe Nanocrystals Using Multidimensional
Electronic Spectroscopy.
AB - The finite spectral line width of an ensemble of CdSe nanocrystals arises from
size and shape inhomogeneity and the single-nanocrystal spectrum itself. This
line width directly limits the performance of nanocrystal-based devices, yet most
optical measurements cannot resolve the underlying contributions. We use two
dimensional electronic spectroscopy (2D ES) to measure the line width of the band
edge exciton of CdSe nanocrystals as a function of radii and surface chemistry.
We find that the homogeneous width decreases for increasing nanocrystal radius
and that surface chemistry plays a critical role in controlling this line width.
To explore the hypothesis that unpassivated trap states serve to broaden the
homogeneous line width and to explain its size-dependence, we use 3D ES to
identify the spectral signatures of exciton-phonon coupling to optical and
acoustic phonons. We find enhanced coupling to optical phonon modes for
nanocrystals that lack electron-passivating ligands, suggesting that localized
surface charges enhance exciton-phonon coupling via the Frohlich interaction.
Lastly, the data reveal that spectral diffusion contributes negligibly to the
homogeneous line width on subnanosecond time scales.
PMID- 28422504
TI - Integrated Computational Approach to the Electron Paramagnetic Resonance
Characterization of Rigid 310-Helical Peptides with TOAC Nitroxide Spin Labels.
AB - We address the interpretation, via an integrated computational approach, of the
experimental continuous-wave electron paramagnetic resonance (cw-EPR) spectra of
a complete set of conformationally highly restricted, stable 310-helical peptides
from hexa- to nonamers, each bis-labeled with nitroxide radical-containing TOAC
(4-amino-1-oxyl-2,2,6,6-tetramethylpiperidine-4-carboxylic acid) residues. The
usefulness of TOAC for this type of analysis has been shown already to be due to
its cyclic piperidine side chain, which is rigidly connected to the peptide
backbone alpha-carbon. The TOAC alpha-amino acids are separated by two, three,
four, and five intervening residues. This set of compounds has allowed us to
modulate both the radical...radical distance and the relative orientation
parameters. To further validate our conclusion, a comparative analysis has been
carried out on three singly TOAC-labeled peptides of similar main-chain length.
PMID- 28422506
TI - Extra-Large Pore Mesoporous Silica Nanoparticles for Directing in Vivo M2
Macrophage Polarization by Delivering IL-4.
AB - Over the past decade, mesoporous silica nanoparticles (MSNs) smaller than 200 nm
with a high colloidal stability have been extensively studied for systemic drug
delivery. Although small molecule delivery via MSNs has been successful, the
encapsulation of large therapeutic biomolecules, such as proteins or DNA, is
limited due to small pore size of the conventional MSNs obtained by soft
templating. Here, we report the synthesis of mesoporous silica nanoparticles with
extra-large pores (XL-MSNs) and their application to in vivo cytokine delivery
for macrophage polarization. Uniform, size-controllable XL-MSNs with 30 nm extra
large pores were synthesized using organic additives and inorganic seed
nanoparticles. XL-MSNs showed significantly higher loadings for the model
proteins with different molecular weights compared to conventional small pore
MSNs. XL-MSNs were used to deliver IL-4, which is an M2-polarizing cytokine and
very quickly degraded in vivo, to macrophages and polarize them to anti
inflammatory M2 macrophages in vivo. XL-MSNs induced a low level of reactive
oxygen species (ROS) production and no pro-inflammatory cytokines in bone marrow
derived macrophages (BMDMs) and in mice injected intravenously with XL-MSNs. We
found that the injected XL-MSNs were targeted to phagocytic myeloid cells, such
as neutrophils, monocytes, macrophages, and dendritic cells. Finally, we
demonstrated that the injection of IL-4-loaded XL-MSNs successfully triggered M2
macrophage polarization in vivo, suggesting the clinical potential of XL-MSNs for
modulating immune systems via targeted delivery of various cytokines.
PMID- 28422507
TI - Chemo-, Regio-, and Enantioselective Rhodium-Catalyzed Allylation of
Pyridazinones with Terminal Allenes.
AB - The rhodium-catalyzed addition of pyridazinones to terminal allenes furnished the
corresponding branched N2-allylated products in good yields with high regio- and
enantioselectivities. A broad functional group compatibility was observed, and
assorted synthetic transformations of the N-allylpyridazinones led to the
preparation of a small library of N2-functionalized pyridazinones. Labeling
experiments with deuterated substrates provided insights into the underlying
reaction mechanism.
PMID- 28422509
TI - alpha-Glucosidase Inhibitors from Salvia circinata.
AB - A dried infusion prepared from the aerial parts of Salvia circinata did not
provoke acute toxicity in mice (LD50 > 5 g/kg). This infusion showed poor
hypoglycemic and antihyperglycemic effects (100-570 mg/kg) when tested in normal
and hyperglycemic mice using acute and oral glucose tolerance tests,
respectively. However, this infusion possessed antihyperglycemic action in vivo
during an oral sucrose tolerance test (31.6-316 mg/kg), suggesting the presence
of alpha-glucosidase inhibitors in S. circinata. Fractionation of a nonpolar
extract of the aerial parts of the plant yielded a new biflavone (1) and four new
neoclerodane diterpenoid glucosides (2-5) along with the known compounds
amarisolide (6), pedalitin (7), apigenin-7-O-beta-d-glucoside (8), and the
flavone 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy-7-methoxy-4H-chromen-4-one (9).
Compounds 1 and 6-9 were active against mammalian alpha-glucosidases; 6 and 7
were also active against a recombinant alpha-glucosidase from Ruminococcus obeum
and reduced significantly the postprandial peak during an oral sucrose tolerance
test in healthy mice, consistent with their alpha-glucosidase inhibitory
activity. Molecular docking and dynamic studies revealed that compounds 6 and 7
might bind to alpha-glucosidases at the catalytic center of the enzyme.
PMID- 28422508
TI - Nitrile in the Hole: Discovery of a Small Auxiliary Pocket in Neuronal Nitric
Oxide Synthase Leading to the Development of Potent and Selective 2
Aminoquinoline Inhibitors.
AB - Neuronal nitric oxide synthase (nNOS) inhibition is a promising strategy to treat
neurodegenerative disorders, but the development of nNOS inhibitors is often
hindered by poor pharmacokinetics. We previously developed a class of membrane
permeable 2-aminoquinoline inhibitors and later rearranged the scaffold to
decrease off-target binding. However, the resulting compounds had decreased
permeability, low human nNOS activity, and low selectivity versus human eNOS. In
this study, 5-substituted phenyl ether-linked aminoquinolines and derivatives
were synthesized and assayed against purified NOS isoforms. 5-Cyano compounds are
especially potent and selective rat and human nNOS inhibitors. Activity and
selectivity are mediated by the binding of the cyano group to a new auxiliary
pocket in nNOS. Potency was enhanced by methylation of the quinoline and by
introduction of simple chiral moieties, resulting in a combination of hydrophobic
and auxiliary pocket effects that yielded high (~500-fold) n/e selectivity.
Importantly, the Caco-2 assay also revealed improved membrane permeability over
previous compounds.
PMID- 28422510
TI - Halide Perovskites for Tandem Solar Cells.
AB - Perovskite solar cells have become one of the strongest candidates for next
generation solar energy technologies. A myriad of beneficial optoelectronic
properties of the perovskite materials have enabled superb power conversion
efficiencies (PCE) exceeding 22% for a single-junction device. The high PCE
achievable via low processing costs and relatively high variability in optical
properties have opened new possibilities for perovskites in tandem solar cells.
In this Perspective, we will discuss current research trends in fabricating
tandem perovskite-based solar cells in combination with a variety of mature
photovoltaic devices such as organic, silicon, and Cu(In,Ga)(S,Se)2 (CIGS) solar
cells. Characteristic features and present limitations of each tandem cell will
be discussed and elaborated upon. Finally, key issues for further improvement and
the future outlook will be discussed.
PMID- 28422511
TI - Semiclathrate Hydrates in Tri-n-butylphosphine Oxide (TBPO)-Water and TBPO-Water
Methane Systems.
AB - In the present work, we studied semiclathrate hydrates in the TBPO-H2O and TBPO
H2O-CH4 systems. The stoichiometry, temperature, and enthalpy of dissociation of
TBPO semiclathrate hydrate crystals formed in the TBPO-H2O binary system were
found to be TBPO.33.6 +/- 0.9H2O, 280.0 K, and 253.1 +/- 4.7 J g-1, respectively.
The crystal structure determined by single crystal XRD analysis (150 K) was the
orthorhombic with space group Pbam and unit cell parameters a = 19.9313(8) A, b =
23.4660(7) A, and c = 12.1127(5) A. The structural stoichiometry is TBPO.34.5H2O.
The TBPO guest molecules arrangement within the host water framework has been
refined for the first time. The discrepancy between the analytically measured and
structural stoichiometry is likely to be attributed to the structure defects,
which cannot be revealed by the routine single-crystal XRD analysis. The methane
capacity of TBPO + CH4 double hydrate was measured by the thermovolumetric method
in the range 14.9-55.8 wt % TBPO aqueous solution at a methane pressure of 8.5 +/
0.5 MPa and temperature of 274 +/- 1 and 286 +/- 1 K. The maximum included
methane volumes of 61.6-74.6 mL/g were observed for the TBPO + CH4 double
hydrates synthesized from ~26-30 wt % TBPO aqueous solutions. Powder X-ray
diffraction measurements of the hydrate samples used in the thermovolumetric
experiments revealed that the TBPO + CH4 double hydrate has the same structural
characteristics as the simple TBPO hydrate. The study of the Raman spectra of the
TBPO + CH4 double hydrate and TBPO simple hydrate showed that in the TBPO + CH4
double hydrate CH4 molecules selectively occupy the small D cages. The results of
the present study did not confirm the earlier suggestion of the formation of
several structural types of hydrates in the TBPO-H2O system. The obtained results
indicate that the TBPO-H2O binary system has a potential for application in gas
separation and as cold storage and transportation media.
PMID- 28422512
TI - Ultrafast Spectroscopic Investigation of Energy Transfer in Site-Directed Mutants
of the Fenna-Matthews-Olson (FMO) Antenna Complex from Chlorobaculum tepidum.
AB - Ultrafast transient absorption (TA) and time-resolved fluorescence (TRF)
spectroscopic studies were performed on several mutants of the
bacteriochlorophyll (BChl) a-containing Fenna-Matthews-Olson (FMO) complex from
the green sulfur bacterium Chlorobaculum tepidum. These mutants were generated to
perturb a particular BChl a site and determine its effects on the optical
spectroscopic properties of the pigment-protein complex. Measurements conducted
at 77 K under both oxidizing and reducing conditions revealed changes in the
dynamics of the various spectral components as compared to the data set from wild
type FMO. TRF results show that under reducing conditions all FMO samples decay
with a similar lifetime in the ~2 ns range. The oxidized samples revealed varying
fluorescence lifetimes of the terminal BChl a emitter, considerably shorter than
those recorded for the reduced samples, indicating that the quenching mechanism
in wild-type FMO is still present in the mutants. Global fitting of TA data
yielded similar overall results, and in addition, the lifetimes of early decaying
components were determined. Target analyses of TA data for select FMO samples
generated kinetic models that better simulate the TA data. A comparison of the
lifetime of excitonic components for all samples reveals that the mutations
affect mainly the early kinetic components, but not that of the lowest energy
exciton, which reflects the flexibility of energy transfer in FMO.
PMID- 28422513
TI - Reducing Susceptibility to Courtesy Stigma.
AB - In light of the chronic shortage of health professionals willing to care for
HIV/AIDS patients, and rising epidemics in many Muslim countries, this
qualitative study examined susceptibility and resistance to courtesy stigma as
experienced by nurses, doctors, and social workers in Morocco. Forty-nine in
depth interviews provided rich insights into the process of courtesy stigma and
how it is managed, within the context of interactions with Islam, interactions
within the workplace (patients, other health professionals), and interactions
outside the workplace (the general public, friends, and family). Theoretically,
the findings extend understanding of courtesy stigma and the dirty work
literature. The findings also offer practical suggestions for the development of
culturally appropriate strategies to reduce susceptibility to courtesy
stigmatization. This study represents the first to explore courtesy stigma as a
process experienced by health professionals providing HIV/AIDS care in an Islamic
country.
PMID- 28422515
TI - Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in
Subjects with Asthma.
AB - RATIONALE: Group 2 innate lymphoid cells (ILC2), a major source of type 2
cytokines, initiate eosinophilic inflammatory responses in murine models of
asthma. OBJECTIVES: To investigate the role of ILC2 in allergen-induced airway
eosinophilic responses in subjects with atopy and asthma. METHODS: Using a
diluent-controlled allergen challenge crossover study, where all subjects (n =
10) developed allergen-induced early and late responses, airway eosinophilia, and
increased methacholine airway responsiveness, bone marrow, blood, and sputum
samples were collected before and after inhalation challenge. MEASUREMENTS AND
MAIN RESULTS: ILC2 (lin-FcepsilonRI-CD45+CD127+ST2+) and CD4+T lymphocytes were
enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression.
Steroid sensitivity of ILC2 and CD4+ T cells was investigated in vitro. A
significant increase in total, IL-5+, IL-13+, and CRTH2+ ILC2 was found in
sputum, 24 hours after allergen, coincident with a significant decrease in blood
ILC2. Total, IL-5+, and IL-13+, but not CRTH2+, CD4+ T cells significantly
increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow,
only CD4+ cells demonstrated increased activation after allergen. Airway
eosinophilia correlated with IL-5+ ILC2 at all time points and allergen-induced
changes in IL-5+ CD4+ cells at 48 hours after allergen. Dexamethasone
significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by
both cell types. CONCLUSIONS: Innate and adaptive immune cells are increased in
the airways associated with allergic asthmatic responses. Total and type 2
cytokine-positive ILC2 are increased only within the airways, whereas CD4+ T
lymphocytes demonstrated local and systemic increases. Steroid sensitivity of
both cells may explain effectiveness of this therapy in those with mild asthma.
PMID- 28422514
TI - Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal
Smoking in Pregnancy.
AB - RATIONALE: Infants whose mothers smoked during pregnancy demonstrate lifelong
decreases in pulmonary function. DNA methylation changes associated with maternal
smoking during pregnancy have been described in placenta and cord blood at
delivery, in fetal lung, and in buccal epithelium and blood during childhood. We
demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier,
NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the
impact of maternal smoking on offspring pulmonary function and decrease the
incidence of wheeze at 1 year of age. OBJECTIVES: To determine whether vitamin C
supplementation reduces changes in offspring methylation in response to maternal
smoking and whether methylation at specific CpGs is also associated with
respiratory outcomes. METHODS: Targeted bisulfite sequencing was performed with a
subset of placentas, cord blood samples, and buccal samples collected during the
NCT00632476 trial followed by independent validation of selected cord blood
differentially methylated regions, using bisulfite amplicon sequencing.
MEASUREMENTS AND MAIN RESULTS: The majority (69.03%) of CpGs with at least 10%
methylation difference between placebo and nonsmoker groups were restored (by at
least 50%) toward nonsmoker levels with vitamin C treatment. A significant
proportion of restored CpGs were associated with phenotypic outcome with greater
enrichment among hypomethylated CpGs. CONCLUSIONS: We identified a pattern of
normalization in DNA methylation by vitamin C supplementation across multiple
loci. The consistency of this pattern across tissues and time suggests a systemic
and persistent effect on offspring DNA methylation. Further work is necessary to
determine how genome-wide changes in DNA methylation may mediate or reflect
persistent effects of maternal smoking on lung function.
PMID- 28422516
TI - Exergaming Through the Eyes of Patients with Heart Failure: A Qualitative Content
Analysis Study.
AB - OBJECTIVE: Exergaming appears to be a promising tool to increase exercise
capacity in patients with chronic heart failure (HF). Therefore, it is important
to obtain more in-depth knowledge about preferences, attitudes, use, and
abilities in regard to exergaming. The aim of this study was to describe the
experiences of patients with HF when using an exergame platform at home.
MATERIALS AND METHODS: A qualitative descriptive study using content analysis was
conducted on interviews with 14 patients with HF (6 women, ages ranging between
56 and 81 years). The patients were recruited from three centers in Sweden
included in a randomized controlled study. These patients had access to an
exergame platform at home and were advised to exergame for 30 minutes per day.
RESULTS: The analysis resulted in three categories describing patients'
experience of exergaming: (1) making exergaming work, (2) added value of
exergaming, and (3) low appeal of exergaming. CONCLUSION: This is the first study
that explores how patients with HF experience using an exergame platform at home.
The study provided important information on what aspects to discuss when
initiating an exergame platform at home and following patients who may want to
use an exergame platform at home. The results also revealed that this technology
may be suitable for some patients, while others prefer other kinds of physical
activity.
PMID- 28422517
TI - Neuropathic pain: a narrative review of etiology, assessment, diagnosis, and
treatment for primary care providers.
AB - BACKGROUND: Neuropathic pain (NeP) is a distinct type of chronic pain that is a
direct result of damage to the nervous system itself. Studies have shown that
training on the topic of chronic pain in medical schools is lacking and many
practitioners are not confident in their ability to effectively manage patients
with such pain. AIMS: The purpose of this narrative review is to provide a brief
high-level overview of NeP for primary healthcare providers that includes a
discussion of mechanisms, prevalence, burden, assessment, and treatment. The
information provided here should help primary care providers better understand
this type of chronic pain.
PMID- 28422518
TI - The Moderating Role of Close versus Distal Peer Injunctive Norms and
Interdependent Self-Construal in the Effects of Descriptive Norms on College
Drinking.
AB - Based on the theory of normative social behavior (Rimal & Real, 2005), this study
examined the effects of descriptive norms, close versus distal peer injunctive
norms, and interdependent self-construal on college students' intentions to
consume alcohol. Results of a cross-sectional study conducted among U.S. college
students (N = 581) found that descriptive norms, close, and distal peer
injunctive norms had independent effects on college students' intentions to
consume alcohol. Furthermore, close peer injunctive norms moderated the effects
of descriptive norms on college students' intentions to consume alcohol and the
interaction showed different patterns among students with a strong and weak
interdependent self-construal. High levels of close peer injunctive norms
weakened the relationship between descriptive norms and intentions to consume
alcohol among students with a strong interdependent self-construal but
strengthened the relationship between descriptive norms and intentions to consume
alcohol among students with a weak interdependent self-construal. Implications of
the findings for norms-based research and college drinking interventions are
discussed.
PMID- 28422519
TI - Spontaneous Hedonic Reactions to Social Media Cues.
AB - Why is it so difficult to resist the desire to use social media? One possibility
is that frequent social media users possess strong and spontaneous hedonic
reactions to social media cues, which, in turn, makes it difficult to resist
social media temptations. In two studies (total N = 200), we investigated less
frequent and frequent social media users' spontaneous hedonic reactions to social
media cues using the Affect Misattribution Procedure-an implicit measure of
affective reactions. Results demonstrated that frequent social media users showed
more favorable affective reactions in response to social media (vs. control)
cues, whereas less-frequent social media users' affective reactions did not
differ between social media and control cues (Studies 1 and 2). Moreover, the
spontaneous hedonic reactions to social media (vs. control) cues were related to
self-reported cravings to use social media and partially accounted for the link
between social media use and social media cravings (Study 2). These findings
suggest that frequent social media users' spontaneous hedonic reactions in
response to social media cues might contribute to their difficulties in resisting
desires to use social media.
PMID- 28422520
TI - Improvement of Performance and Reduction of Fatigue With Low-Level Laser Therapy
in Competitive Cyclists.
AB - Evidence indicates that low-level laser therapy (LLLT) minimizes fatigue effects
on muscle performance. However, the ideal LLLT dosage to improve
athletes'performance during sports activities such as cycling is still unclear.
Therefore, the goal of this study was to investigate the effects of different
LLLT dosages on cyclists'performance in time-to-exhaustion tests. In addition,
the effects of LLLT on the frequency content of the EMG signals to assess fatigue
mechanisms were examined. Twenty male competitive cyclists participated in a
crossover, randomized, double-blind, placebo-controlled trial. They performed an
incremental cycling test to exhaustion (on day 1) followed by 4 time-to
exhaustion tests (on days 2-5) at their individual maximal power output. Before
each time-to-exhaustion test, different dosages of LLLT (135, 270, and 405
J/thigh, respectively) or placebo were applied at the quadriceps muscle
bilaterally. Power output and muscle activation from both lower limbs were
recorded throughout the tests. Increased performance in time-to-exhaustion tests
was observed with the LLLT-135 J (~22 s; P < .01), LLLT-270 J (~13 s; P = .03),
and LLLT-405 J (~13 s; P = .02) compared to placebo (149 +/- 23 s). Although LLLT
270 J and LLLT-405 J did not show significant differences in muscle activation
compared with placebo, LLLT-135 J led to an increased high-frequency content
compared with placebo in both limbs at the end of the exhaustion test (P <= .03).
In conclusion, LLLT increased time to exhaustion in competitive cyclists,
suggesting this intervention as a possible nonpharmacological ergogenic agent in
cycling. Among the different dosages, LLLT-135 J seems to promote the best
effects.
PMID- 28422521
TI - Different approaches to the assessment of adherence and persistence with
cardiovascular-disease preventive medications.
AB - OBJECTIVE: To assess suitability and comparability of the most common methods of
treatment adherence and persistence assessment, as applied to the same pharmacy
dataset. METHODS: Data on drugs prescribed for cardiovascular primary prevention
to participants in the Aragon Workers' Health Study (AWHS) were collected from a
regional electronic drug prescription database. Several different approaches were
used to measure treatment adherence (with the medication possession ratio [MPR])
and proportion of days covered [PDC]) and persistence in new users by therapeutic
subgroup. Defined daily dose (DDD) was used as a proxy of the number of days'
supply, or substituted with surrogate daily dose values. RESULTS: Higher mean
adherence values and proportions of adherent patients were obtained using MPR
versus PDC, with additional differences depending on the approach used. The
proportion of adherent patients was lowest for oral antidiabetics (14.4%-30.6%)
and highest for antihypertensives (70.2%-82.1%). The use of surrogate daily dose
values increased adherence for antidiabetics and statins and decreased adherence
for antihypertensives. After a 1 year follow-up, treatment persistence was
observed for 21.1%, 58.7%, and 29.5% of antidiabetic, antihypertensive and statin
users, respectively. CONCLUSIONS: Our findings indicate that use of multiple
measures of treatment adherence and persistence provides a more complete overview
of medication use patterns, and certain limitations associated with DDD for some
drug groups can be overcome with replacement by surrogate doses. The PDC
indicator seems to provide a more accurate reflection of patient behavior and
treatment continuity than the MPR. Any comparison of adherence/persistence should
always consider the method used, variables analyzed, and corresponding data
collection process.
PMID- 28422522
TI - Molecular Genetic Characterization of a Chinese Family with Severe Split
Hand/Foot Malformation.
AB - AIMS: Split hand/foot malformation (SHFM) is a congenital limb malformation
characterized by underdeveloped or absent central digital rays, clefts of the
hands and feet, and variable syndactyly of the remaining digits. SHFM is a
genetically heterogeneous disease; the aim of this study was to identify
pathogenic variations in a Chinese family with SHFM. MATERIALS AND METHODS:
Haplotype analyses with microsatellite markers covering the five SHFM loci were
performed to localize the causative locus. Real-time quantitative polymerase
chain reaction (qPCR) assays and inverse PCR were performed to determine the copy
number variations and to amplify junction breakpoints in affected individuals.
Candidate genes were further screened for mutations through Sanger sequencing.
RESULTS: A potential haplotype in the SHFM3 locus was shared by all affected
individuals. qPCR and inverse PCR showed a microduplication at chromosome 10q24
spanning 488,859 bp and encompassing five entire genes, LBX1, BTRC, POLL, DPCD,
and FBXW4, that co-segregated with the SHFM phenotype. No coding or splice-site
mutations of these genes were found. CONCLUSION: We determined the molecular
basis of SHFM in a Chinese family by haplotype analysis, qPCR, inverse PCR, and
Sanger sequencing. Our work extends the clinical spectrum of SHFM3; provides a
fine-scale delineation of the chromosomal breakpoints helping to narrow the
critical region of SHFM3; and facilitates an understanding of the mechanisms
underlying abnormal limb development and extraskeletal anomalies.
PMID- 28422523
TI - Can the Lamberts and Lambert Submaximal Cycle Test Reflect Overreaching in
Professional Cyclists?
AB - CONTEXT: The Lamberts and Lambert Submaximal Cycle Test (LSCT) consists of 3
stages during which cyclists cycle for 6 min at 60%, 6 min at 80%, and 3 min at
90% of their maximal heart rate, followed by 1-min recovery. PURPOSE: To
determine if the LSCT is able to reflect a state of functional overreaching in
professional female cyclists during an 8-d training camp and the following
recovery days. METHODS: Six professional female cyclists performed an LSCT on
days 1, 5, and 8 of the training camp and 3 d after the training camp. During
each stage of the LSCT, power output and rating of perceived exertion (RPE) were
determined. Training diaries and Profile of Mood States (POMS) were also
completed. RESULTS: At the middle and the end of the training camp, increased
power output during the 2nd and 3rd stages of the LSCT was accompanied with
increased RPE during these stages and/or the inability to reach 90% of maximal
heart rate. All athletes reported increased feelings of fatigue and muscle
soreness, while changes in energy balance, calculated from the POMS, were less
indicative of a state of overreaching. After 3 d of recovery, all parameters of
the LSCT returned to baseline, indicating a state of functional overreaching
during the training camp. CONCLUSION: The LSCT is able to reflect a state of
overreaching in elite professional female cyclists during an 8-d training camp
and the following recovery days.
PMID- 28422524
TI - Straight-Line and Change-of-Direction Intermittent Running in Professional Soccer
Players.
AB - PURPOSE: To investigate the difference between straight-line (STL) and change-of
direction (COD) intermittent-running exercises in soccer players. METHODS:
Seventeen male professional soccer players performed the agility T test and 6
intermittent-running exercises: 10 s at 130% of maximal aerobic speed (MAS)
alternated with 10 s of rest (10-10), 15 s at 120% of MAS alternated with 15 s of
rest (15-15), and 30 s at 110% of MAS alternated with 30 s of rest (30-30) both
in STL and with COD. All exercises were monitored using a global positioning
system. Heart rate was measured during exercises, and rating of perceived
exertion (RPE) was collected postexercise. The difference (Delta) between covered
distance in STL and COD exercises at a similar load was calculated, and
relationships between T test and Delta distance were analyzed. RESULTS: COD
intermittent exercises showed a significantly decreased distance covered and an
increase in the number of accelerations, peak heart rate, and RPE compared with
STL intermittent exercises at a similar load. High relationships were observed
between T-test performance and Delta distance in 10-10 (r = .72, P < .01) and 15
15 (r = .77, P < .01), whereas no significant relationships were observed between
T-test performance and Delta distance in 30-30 (r = -.37, P = .2). CONCLUSION:
Intermittent COD exercises were associated with higher acceleration, peak heart
rate, and RPE than STL during 10-10 and 15-15 exercises. The ability to rapidly
change direction is crucial to perform intense sport-specific running in
professional soccer players.
PMID- 28422525
TI - Soccer Match Play as an Important Component of the Power-Training Stimulus in
Premier League Players.
AB - PURPOSE: Competitive match play is a dominant component of the physical load
completed by soccer players in a training microcycle. Characterizing the temporal
disruption in homeostasis that follows exercise may provide some insight on the
potential for match play to elicit an adaptive response. METHODS: Countermovement
jump (CMJ) performance was characterized 3 d postmatch for 15 outfield players
from an English Premier League soccer team (age 25.8 +/- 4.1 y, stature 1.78 +/-
0.08 m, body mass: 71.7 +/- 9.1 kg) across a season. These players were
classified as either starters (n = 9) or nonstarters (n = 6), according to their
average individual playing time (more or less than 60 min/match). Linear mixed
models were used to investigate the influence of indicators of match activity
(total distance covered [TD] and high-intensity running distance [HI]) on CMJ
height and peak power (PP). RESULTS: Starting players covered much greater TD (ES
= 1.5) and HI (ES = 1.4) than nonstarters. Furthermore, there was a possible
positive effect of HI on CMJ height and PP. This relationship suggests that an
additional 0.6 km of HI would increase CMJ height and PP by slightly more than
the smallest-worthwhile-change values of 0.6 cm and 1.0 W/kg, respectively. This
small yet practically relevant increase in performance may suggest that match
play, more specifically the intense activities that are associated with the
match, provides a physiological stimulus for neuromuscular adaptation.
CONCLUSIONS: These data may have implications for the preparation of soccer
squads, especially the training requirements of starting and nonstarting players.
PMID- 28422526
TI - Acupuncture on Renal Function in Patients with Chronic Kidney Disease: A Single
Blinded, Randomized, Preliminary Controlled Study.
AB - OBJECTIVE: To evaluate the feasibility effect of acupuncture on renal function in
patients with chronic kidney disease (CKD). METHODS: In total, 59 patients with
CKD were randomized into acupuncture (AG; n = 30) and sham acupuncture (CG; n =
29) treatment groups. In the AG, acupuncture was applied to bilateral Hegu (LI4),
Zusanli (ST36), and Taixi (KI3) to obtain qi, and electroacupuncture (2 Hz) was
applied to two acupoint pairs (right Zusanli and Taixi and left Zusanli and
Taixi) once per week for 12 weeks. In the CG, the acupuncture methods were
identical to in the AG, and the acupuncture needle was applied to the
subcutaneous layer at 1.5 cm lateral to the aforementioned acupoints, without
electrical discharge. The levels of serum creatinine and estimated glomerular
filtration rate (eGFR) were measured at 3 months (observation period; O),
immediately before the acupuncture treatment (baseline; B), at 12 weeks (after
treatment completion; T12), and at the 3-month follow-up (postacupuncture
treatment; P). RESULTS: In total, 53 patients (AG, n = 28; CG, n = 25) with CKD
completed the trial. The serum creatinine levels at baseline (B) were 1.45 mg/dL
in the AG and 1.67 mg/dL in the CG (p = 0.1298). Furthermore, the change in serum
creatinine levels after the acupuncture treatment (T12) was 1.41 mg/dL in the AG
and 1.65 mg/dL in the CG (p = 0.0489). The eGFR at baseline was 51.85 mL/min/1.73
m2 in the AG and 42.50 mL/min/1.73 m2 in the CG (p = 0.0855). The change in the
eGFR after the acupuncture treatment was 54.50 mL/min/1.73 m2 in the AG and 43.60
mL/min/1.73 m2 in the CG (p = 0.0470). CONCLUSION: Acupuncture at bilateral Hegu,
Zusanli, and Taixi for 12 weeks reduced creatinine levels and increased eGFR
levels. The study only provided a feasibility method for the treatment of
patients with CKD. However, the results of this preliminary study warrant further
investigation.
PMID- 28422527
TI - Attitudes Toward Stimulant Treatment of Offspring of Adult Patients with
Attention-Deficit/Hyperactivity Disorder.
AB - AIM: The objective of this study was to investigate how adult patients with
attention-deficit/hyperactivity disorder viewed the testing and use of stimulants
in their children. METHODS: Using a qualitative approach, we interviewed 32
outpatients from a special care unit of a university hospital. RESULTS: Emerging
themes centered around concerns about the right age to test children and opinions
about stimulant treatment ranging from unreserved agreement to reluctance, as
well as the need for a shared decision with the child. CONCLUSIONS: Our results
suggest that better psychoeducational programs are needed, especially for adults
with attention-deficit/hyperactivity disorder, in which long-term consequences of
the disorder, areas of impairment, and possible treatment effects in their
children are explained and concerns about unknown side effects and the right time
to test and treat are addressed.
PMID- 28422528
TI - Effect of Psychopharmacotherapy on Body Mass Index Among Children and Adolescents
with Bipolar Disorders.
AB - OBJECTIVE: To assess the long-term effect of all treatment options for pediatric
bipolar disorders on body mass index (BMI) and to explore individual
characteristics associated with less BMI increase during psychotropic medication
exposures. METHODS: A retrospective cohort study was conducted by using the 1995
to 2010 General Electric Electronic Medical Record database. Individuals aged 18
years or younger who had a new bipolar disorder episode were identified.
Treatment exposure was defined based on the medication regimens patients
received, which include atypical antipsychotic (AT) monotherapy, mood stabilizer
(MS) monotherapy, antidepressant (AD) monotherapy, AT+MS polytherapy, AT+AD
polytherapy, MS+AD polytherapy, and no treatment. Both treatment exposure and BMI
were coded as time varying, which could change from month to month. According to
the duration of treatment and the availability of BMI measures, individuals were
followed for up to 3, 6, 9, and 12 months since the treatment initiation.
Repeated-measures mixed models were applied to compare the impact of different
medication regimens and the length of drug exposure on BMI after adjusting for
the baseline BMI, sociodemographic factors, comorbidities, and psychotherapy.
RESULTS: A total of 2299 treated and 4544 untreated children and adolescents who
met the inclusion criteria were identified. Analysis using repeated-measures
mixed models showed that those on AT monotherapy (the reference group) had a
gradually diminished, but statistically significant, monthly increase in BMI
during all durations of drug exposure (3 months: 0.36 kg/m2, 6 months: 0.20
kg/m2, 9 months: 0.17 kg/m2, and 12 months: 0.16 kg/m2). As compared with AT
monotherapy, the magnitude of increase in BMI associated with MS, AD monotherapy,
and no treatment was significantly less at all time points, indicating less steep
slopes of BMI change over time compared with AT monotherapy, especially during
the short-term exposure. The combinations of AT with other psychotropic
medications (ATMS, ATAD) were associated with a similar BMI increase as AT
monotherapy. Individual characteristics found to be associated with a less
increase in BMI during psychotropic medication exposure were being younger and
having a higher baseline BMI. CONCLUSION: The long-term use of atypical
antipsychotics, both as monotherapy or in combination with other psychotropic
medications in children and adolescents with bipolar disorder, was associated
with a steady and cumulative increase in BMI.
PMID- 28422529
TI - Implant compositions for the unidirectional delivery of drugs to the brain.
AB - The overall objective of this study was to design and characterize the properties
of a bioadhesive trilayer sustained-release implant device for the unidirectional
local delivery of anticancer compounds to the brain following the removal of
glioblastoma multiforme tumors. Using acetaminophen as a model drug compound, we
compressed trilayer wafers that contained (i) a bioadhesive layer, (ii) a drug
layer that contained a lipid and a pore-forming hydrophilic polymer, and (iii) a
third layer comprising a lipid substance. To maintain a unidirectional pathway of
drug release from these trilayer wafers, the edges and the surface lipophilic
layer were coated with molten wax followed by cooling of the wafer. These wafers
were subsequently heat cured to promote interlayer adhesion in the device.
Polyethylene oxide was utilized both as the bioadhesive layer and the pore
forming hydrophilic polymer. Glyceryl behenate was employed as the lipid. The
drug release properties of the trilayer wafer were a function of (i) the
molecular weight and concentration of polyethylene oxide in the drug-containing
lipid layer, (ii) the presence of the bioadhesive layer on the wafer, and (iii)
the lipid coating applied to the top and sides of the delivery system. The
unidirectional release of the drug occurred from the device through the
bioadhesive layer, and zero-order release kinetics resulted over a 10-day period
after a 3-day lag time. During this period, <10% of the drug had been released
from the wafer. All of the drug was released by 21 days.
PMID- 28422530
TI - Physiological Changes Following Competition in Male and Female Physique Athletes:
A Pilot Study.
AB - The purpose of the current study was to evaluate changes in body composition,
metabolic rate, and hormones during postcompetition recovery. Data were collected
from natural physique athletes (7 male/8 female) within one week before (T1)
competition, within one week after (T2), and 4-6 weeks after (T3) competition.
Measures included body composition (fat mass [FM] and lean mass [LM] from
ultrasongraphy), resting metabolic rate (RMR; indirect calorimetry), and salivary
leptin, testosterone, cortisol, ghrelin, and insulin. Total body water (TBW;
bioelectrical impedance spectroscopy) was measured at T1 and T2 in a subsample (n
= 8) of athletes. Significant (p < .05) changes were observed for weight (T1 =
65.4 +/- 12.2 kg, T2 = 67.4 +/- 12.6, T3 = 69.3 +/- 13.4; T3 > T2 > T1), LM (T1 =
57.6 +/- 13.9 kg, T2 = 59.4 +/- 14.2, T3 = 59.3 +/- 14.2; T2 and T3 > T1), and FM
(T1 = 7.7 +/- 4.4 kg, T2 = 8.0 +/- 4.4, T3 = 10.0 +/- 6.2; T3 > T1 and T2). TBW
increased from T1 to T2 (Delta=1.9 +/- 1.3 L, p < .01). RMR increased from
baseline (1612 +/- 266 kcal/day; 92.0% of predicted) to T2 (1881 +/- 329, 105.3%;
p < .01) and T3 (1778 +/- 257, 99.6%; p < .001). Cortisol was higher (p < .05) at
T2 (0.41 +/- 0.31 MUg/dL) than T1 (0.34 +/- 0.31) and T3 (0.35 +/- 0.27). Male
testosterone at T3 (186.6 +/- 41.3 pg/mL) was greater than T2 (148.0 +/- 44.6, p
= .04). RMR changes were associated (p <= .05) with change in body fat percent
(DeltaBF%; r = .59) and T3 protein intake (r= .60); male testosterone changes
were inversely associated (p<= .05) with DeltaBF%, DeltaFM, and Deltaweight (r=
0.81--0.88). TBW increased within days of competition. Precompetition RMR
suppression appeared to be variable and markedly reversed by overfeeding, and
reverted toward normal levels following competition. RMR and male testosterone
increased while FM was preferentially gained 4-6 weeks postcompetition.
PMID- 28422531
TI - Femoroacetabular Impingement in Professional Football Players: Return to Play and
Predictors of Career Length After Hip Arthroscopy.
AB - BACKGROUND: Previous studies have shown hip arthroscopy to be a highly effective
treatment for symptomatic femoroacetabular impingement (FAI) in a wide range of
athletes; however, the rate of return to play and length of career after hip
arthroscopy in professional football players are unknown. PURPOSE: To determine
how many athletes returned to professional football and the number of seasons
they played after surgery. STUDY DESIGN: Case series; Level of evidence, 4.
METHODS: Fifty-one professional football players (60 hips) underwent hip
arthroscopy for FAI between 2000 and 2014 by a single surgeon. Return to play was
defined as competing in a preseason or regular season professional football game
after surgery. Data were retrospectively obtained for each player from NFL.com ,
ESPN.com , individual team websites, and/or CFL.ca . RESULTS: We found that 87%
(52/60) of the arthroscopic procedures allowed professional football players to
return to play in a preseason or regular season game. Athletes who returned
played an average of 38 games during 3.2 seasons after arthroscopy, with an
average total career length of 7.4 seasons. Ninety-two percent (48/52) of players
who returned had a minimum total career length of 3 years. When participants were
analyzed by position, linemen were less likely to return after hip arthroscopy
compared with other players (odds ratio 5.6; 95% CI, 1.1-35; P = .04). All
quarterbacks and tight ends returned to play after surgery. No significant
difference in return to play rate was found between athletes who underwent
microfracture and those who did not (25% vs 38%, P = .698). CONCLUSION: Hip
arthroscopy for treatment of FAI and associated pathologic abnormalities in
professional football players resulted in a high rate of return to play. The
study's findings demonstrate that 87% of the arthroscopic procedures allowed
professional football players to return to play, linemen were less likely to
return compared with other positions, and the presence of microfracture did not
significantly affect the return to play rate. These findings support hip
arthroscopy as an effective procedure to treat FAI and related pathologic
abnormalities in the professional football player, and this information is
important for proper counseling of athletes with FAI.
PMID- 28422532
TI - Effects of Postexercise Protein Intake on Muscle Mass and Strength During
Resistance Training: Is There an Optimal Ratio Between Fast and Slow Proteins?
AB - While effects of the two classes of proteins found in milk (i.e., soluble
proteins, including whey, and casein) on muscle protein synthesis have been well
investigated after a single bout of resistance exercise (RE), the combined
effects of these two proteins on the muscle responses to resistance training (RT)
have not yet been investigated. Therefore, the aim of this study was to examine
the effects of protein supplementation varying by the ratio between milk soluble
proteins (fast-digested protein) and casein (slow-digested protein) on the muscle
to a 9-week RT program. In a double-blind protocol, 31 resistance-trained men,
were assigned to 3 groups receiving a drink containing 20g of protein comprising
either 100% of fast protein (FP(100), n = 10), 50% of fast and 50% of slow
proteins (FP(50), n = 11) or 20% of fast protein and 80% of casein (FP(20), n =
10) at the end of training bouts. Body composition (DXA), and maximal strength in
dynamic and isometric were analyzed before and after RT. Moreover, blood plasma
aminoacidemia kinetic after RE was measured. The results showed a higher leucine
bioavailability after ingestion of FP(100) and FP(50) drinks, when compared with
FP(20) (p< .05). However, the RT-induced changes in lean body mass (p < .01),
dynamic (p < .01), and isometric muscle strength (p < .05) increased similarly in
all experimental groups. To conclude, compared with the FP(20) group, the higher
rise in plasma amino acids following the ingestion of FP(100) and FP(50) did not
lead to higher muscle long-term adaptations.
PMID- 28422533
TI - Effect of Resistance Training Systems on Oxidative Stress in Older Women.
AB - The purpose of this study was to investigate the effect of two different
resistance training (RT) systems on oxidative stress biomarkers in older women.
Fifty-nine older women (67.9 +/- 5.0 years) were randomly assigned to one of
three groups. Two training groups performed an 8 week RT program either in
traditional (TD, n = 20) or a pyramid (PR, n = 20) system 3 times per week, or a
control group (CG, n = 19). The TD program consisted of 3 sets of 8-12 RM with
constant load for the 3 sets, whereas the PR training consisted of 3 sets of
12/10/8 RM with incremental loads for each set. As compared with the CG, both TD
and PR achieved upregulation of the antioxidant system as evidenced by higher (p
< .05) values of total radical-trapping antioxidant parameter plasma
concentration after intervention (TD= 930.4 +/- 160.0 umolTrolox, PR= 977.8 +/-
145.2 umolTrolox, CG= 794.4 +/- 130.2 umolTrolox). For the protein oxidation
adducts, TD and PR presented lower (p < .05) scores compared with CG (TD= 91.2 +/
25.0 umol/L, PR= 93.0 +/- 30.3 umol/L, CG= 111.0 +/- 20.4 umol/L). However,
there were no differences (p < .05) between trained groups in the antioxidant
capacity markers and in the protein oxidation adducts markers. The results
suggest that 8 weeks of progressive RT promotes an improvement in markers of
oxidative stress in older women independent of the load-management RT system.
PMID- 28422534
TI - In Situ Sampling of Relative Dust Devil Particle Loads and Their Vertical Grain
Size Distributions.
AB - During a field campaign in the Sahara Desert in southern Morocco, spring 2012, we
sampled the vertical grain size distribution of two active dust devils that
exhibited different dimensions and intensities. With these in situ samples of
grains in the vortices, it was possible to derive detailed vertical grain size
distributions and measurements of the lifted relative particle load. Measurements
of the two dust devils show that the majority of all lifted particles were only
lifted within the first meter (~46.5% and ~61% of all particles; ~76.5 wt % and
~89 wt % of the relative particle load). Furthermore, ~69% and ~82% of all lifted
sand grains occurred in the first meter of the dust devils, indicating the
occurrence of "sand skirts." Both sampled dust devils were relatively small (~15
m and ~4-5 m in diameter) compared to dust devils in surrounding regions;
nevertheless, measurements show that ~58.5% to 73.5% of all lifted particles were
small enough to go into suspension (<31 MUm, depending on the used grain size
classification). This relatively high amount represents only ~0.05 to 0.15 wt %
of the lifted particle load. Larger dust devils probably entrain larger amounts
of fine-grained material into the atmosphere, which can have an influence on the
climate. Furthermore, our results indicate that the composition of the surface,
on which the dust devils evolved, also had an influence on the particle load
composition of the dust devil vortices. The internal particle load structure of
both sampled dust devils was comparable related to their vertical grain size
distribution and relative particle load, although both dust devils differed in
their dimensions and intensities. A general trend of decreasing grain sizes with
height was also detected.
PMID- 28422535
TI - Comparison between normal saline and Ringer's acetate in bipolar transurethral
resection of the prostate.
AB - OBJECTIVE: The standard surgical treatment for benign prostatic hypertrophy (BPH)
is transurethral resection of the prostate (TURP). The aim of this study was to
compare normal saline (NS) (0.9% sodium chloride) and Ringer's acetate (RA) as
irrigation fluid with regard to visibility, resection feasibility, coagulation
and bleeding in bipolar TURP. MATERIALS AND METHODS: Twenty patients (mean age 70
years) who were diagnosed with BPH were recruited to the study. The first three 3
liter bags of irrigation fluid contained either NS or RA and were administered in
a randomized fashion. The surgeon assessed visibility, bleeding, coagulation,
resection efficacy and overall outcome after each 3 liter bag on a scale of 1-10.
RESULTS: The results disclosed only marginal differences between the two fluids
with regard to the recorded parameters. All of the differences lacked statistical
significance (p > .05). CONCLUSION: RA can be used as an irrigation fluid in
bipolar TURP with no obvious difference in comparison with NS.
PMID- 28422536
TI - Impact of Lifestyle Strategies on Longer-Term Physical Activity and Weight.
AB - BACKGROUND: Lifestyle interventions promote increased physical activity (PA) and
weight loss; however, relapse to sedentary behavior and weight regain are common.
METHODS: We analyzed baseline and 24-month data from participants in the Slow the
Adverse Vascular Effects (SAVE) study. SAVE included an 18-month behavioral
intervention. At 24 months, participants completed a survey about lifestyle
strategies used in past 6 months. PA levels were assessed with the Modifiable
Activity Questionnaire. We compared change in weight, BMI, and PA from baseline
to 24 months by use of strategies vs. no use. RESULTS: 214 participants (61%)
completed 24-month visit. 74% were female and 86% were white. At 24 months, 65%
used self-monitoring, 67% group/commercial support, 94% other behavioral skills,
and 27% used professional support within past 6 months. At 24 months,
participants who used self-monitoring (5.2 vs. -0.8 MET-hr/wk; P = .001) and
group/commercial support (4.3 vs. 0 MET-hrs/wk; P = .01) had greater PA increases
compared with those who did not use strategies. Participants who used other
behavioral strategies had a significantly greater percent decrease in weight than
those who did not. CONCLUSIONS: Of the lifestyle strategies used following
intervention, self-monitoring and group/commercial support may be particularly
important in longer-term PA levels.
PMID- 28422538
TI - An Examination of Exercise-Induced Feeling States and Their Association With
Future Participation in Physical Activity Among Older Adults.
AB - Although exercise-induced feeling states may play a role in driving future
behavior, their role in relation to older adults' participation in physical
activity (PA) has seldom been considered. The objectives of this study were to
describe changes in older adults' feeling states during exercise, and examine if
levels of and changes in feeling states predicted their future participation in
PA. Self-reported data on feeling states were collected from 82 older adults
immediately before, during, and after a moderate-intensity exercise session, and
on participation in PA 1 month later. Data were analyzed using latent growth
modeling. Feelings of revitalization, positive engagement, and tranquility
decreased during exercise, whereas feelings of physical exhaustion increased.
Feelings of revitalization immediately before the exercise session predicted
future participation in PA; changes in feeling states did not. This study does
not provide empirical evidence that older adults' exercise-induced feeling states
predict their future participation in PA.
PMID- 28422537
TI - Morbidity and Mortality Associated with Prehospital "Lift-assist" Calls.
AB - INTRODUCTION: When an individual requires assistance with mobilization, emergency
medical services (EMS) may be called. If a patient does not receive treatment on
scene and is not transported to hospital, these are referred to as "Lift Assist"
(LA) calls. It is possible this need for assistance represents a subtle onset of
a disease process or decline in function. Without recognition or treatment, the
patient may be at risk for recurrent falls, repeat EMS visits or worsening
illness. OBJECTIVE: To examine the 14-day morbidity and mortality associated with
LA calls and determine factors that are associated with increased risk of these
outcomes. METHODS: All LA calls from a single EMS agency were collected over a
one year study period (January-December 2013). Calls were linked with hospital
records to determine if LA patients had a subsequent visit to the emergency
department (ED), admission, or death within 14 days of the LA call. Logistic
regression analyses were completed to determine factors predicting ED visit or
hospital admission within 14 days of the LA call. RESULTS: Of 42,055 EMS calls,
804 (1.9%) were LAs. These calls were for 414 individuals; 298 (72%) patients had
1 LA, and 116 (28%) patients had >1 LA call. There were 169 (21%) ED visits, 93
(11.6%) hospital admissions and 9 (1.1%) deaths within 14 days of a LA call.
Patient age (p = 0.025) significantly predicted ED visit. Patient age (p = 0.006)
and an Ambulance Call Record missing at least 1 vital sign (p = 0.038)
significantly predicted hospital admission. CONCLUSIONS: LA calls are associated
with short-term morbidity and mortality. Patient age was found to be associated
with these outcomes. These calls may be early indicators of problems requiring
comprehensive medical evaluation and thus further factors associated with poor
outcomes should be determined.
PMID- 28422540
TI - Evaluating Barriers to Bystander CPR among Laypersons before and after
Compression-only CPR Training.
AB - OBJECTIVE: Bystander CPR is an essential part of out-of-hospital cardiac arrest
(OHCA) survival. EMS and public safety jurisdictions have embraced initiatives to
teach compression-only CPR to laypersons in order to increase rates of bystander
CPR. We examined barriers to bystander CPR amongst laypersons participating in
community compression-only CPR training and the ability of the training to
alleviate these barriers. The barriers analyzed include fear of litigation, risk
of disease transmission, fear of hurting someone as a result of doing CPR when
unnecessary, and fear of hurting someone as a result of doing CPR incorrectly.
METHODS: Laypersons attending community compression-only CPR training were
administered surveys before and after community CPR training. Data were analyzed
via standard statistical analyses. RESULTS: A total of 238 surveys were collected
and analyzed between September 2015 and January 2016. The most common reported
motivation for attending CPR training was "to be prepared/just in case" followed
by "infant or child at home." Respondents reported that they were significantly
more likely to perform CPR on a family member than a stranger in both pre-and
post-training responses. Nevertheless, reported self-confidence in and likelihood
of doing CPR on both family and strangers increased from pre-training to post
training. There was a statistically significant decrease in reported likelihood
of all four barriers to prevent respondents from performing bystander CPR when
pre-training responses were compared to post-training responses. Previous CPR
training and history of having witnessed a sudden cardiac arrest (SCA) were both
associated with decreased barriers to CPR, but previous training had no effect on
reported likelihood of or confidence in performing CPR. CONCLUSION: The training
initiative studied significantly reduced the reported likelihood of all barriers
studied to prevent respondents from performing bystander CPR and also increased
the reported confidence in doing CPR and likelihood of doing CPR on both
strangers and family. However, it did not alleviate the pre-training discrepancy
between likelihood of performing CPR on strangers versus family. Previous CPR
training or certification had no impact on likelihood of or confidence in
performing CPR.
PMID- 28422539
TI - The Effect of Nitrate Supplementation on Cycling Performance in the Heat in Well
Trained Cyclists.
AB - PURPOSE: To determine the effect of [Formula: see text] consumption on measures
of perception, thermoregulation, and cycling performance in hot conditions.
METHODS: In a randomized, double-blind, crossover design, 8 well-trained cyclists
(mean +/- SD age 25 +/- 8 y, [Formula: see text] peak 64 +/- 5 mL . kg-1 . min-1)
performed 2 separate trials in hot (35 degrees C, 60% relative humidity)
environments, having ingested either 140 mL [Formula: see text]-rich beetroot
juice ~8 mmol [Formula: see text] (NIT) or placebo (PLA) daily for 3 d with a 7-d
washout period separating trials. Trials consisted of 2 * 10-min bouts at 40% and
60% peak power output (PPO) to determine physiological and perceptual responses
to the heat, followed by a 4-km cycling time trial. RESULTS: Basal [nitrite] was
substantially elevated in NIT (2.70 +/- 0.98 uM) vs PLA (1.10 +/- 0.61 uM),
resulting in a most likely (ES = 1.58 +/- 0.93) increase after 3 d. There was a
very likely trivial increase in rectal temperature in NIT at 40% (PLA 37.4
degrees C +/- 0.2 degrees C vs NIT 37.5 degrees C +/- 0.3 degrees C, 0.1 degrees
C +/- 0.2 degrees C) and 60% (PLA 37.8 degrees C +/- 0.2 degrees C vs NIT 37.9
degrees C +/- 0.3 degrees C, 0.1 degrees C +/- 0.2 degrees C) PPO. Cycling
performance was similar between trials (PLA 336 +/- 45 W vs NIT 337 +/- 50 W, CV
+/- 95%CL; 0.2% +/- 2.5%). Outcomes for heart rate and perceptual measures were
unclear across the majority of time points. CONCLUSIONS: Three days of [Formula:
see text] supplementation resulted in small increases in rectal temperature
during low- to moderate-intensity exercise, but this did not appear to influence
4-km cycling time-trial performance in hot climates.
PMID- 28422541
TI - Evaluation of the Implementation of the Trauma Triage and Destination Plan on the
Field Triage of Injured Patients in North Carolina.
AB - OBJECTIVE: Timely triage and appropriate destination decision making for injured
patients are central challenges faced by emergency medical services (EMS)
systems. In 2010, North Carolina (NC) adopted a statewide Trauma Triage and
Destination Plan (TTDP) based on the CDC's Field Triage Guidelines to better
address these challenges. We sought to characterize the implementation of these
guidelines by quantifying their effect on multiple metrics of patient care.
METHODS: We employed a retrospective pre-post study design utilizing a statewide
EMS medical record database. We assessed several metrics of patient care
including changes in destination choice, appropriateness of EMS destination,
transit time to first hospital, transit time to definitive care, and others-in a
six-month period in the year before and after the implementation of the
guidelines. RESULTS: We evaluated a total of 190,307 EMS encounters pre- (n =
93,927) and post-implementation (n = 96,380). Among all patients, there was not a
significant difference in the percentage transported to a community hospital or
Level I, II, or III trauma center as their first destination. Among those
patients meeting TTDP guidelines for transport to a trauma center, the number
transported to a Level I or II trauma center decreased 1.0% from 30.6% (n =
2,911) to 29.6% (n = 2,954) (95% CI: -0.2%, 2.2%). Those transported to a Level I
trauma center decreased 0.4% from 21.2% to 20.8% in the post-period (95% CI:
0.7%, 1.5%). There were also no significant changes in EMS scene times (14.0 pre
, 14.1 post-) and transport times (12.9 pre-, 13.0 post-). While scene distance
from a Level I trauma center showed a decreased likelihood of transport to that
center, there was an overall post-implementation increase of 2.5% from 18.0% to
20.5% (95% CI: -3.6%, -1.3%) in transport to a Level I trauma center among
patients meeting anatomic criteria across all distance ranges. CONCLUSIONS: We
found that implementation of region-specific destination plans based on the Field
Triage Guidelines had little effect on selected hospital destination, scene
times, transport times, and other metrics of EMS decision making and
effectiveness. We suspect this is due to delays in information dissemination and
adoption by field providers.
PMID- 28422542
TI - Routine Yoga Practice Impacts Whole Body Protein Utilization in Healthy Women.
AB - Whole body protein utilization (WBPU), which includes flux (Q), protein synthesis
(PS), protein breakdown (PB), and whole body protein balance (WBPB), provides
insight regarding muscle mass, a criterion for sarcopenia. To characterize yoga's
impact on WBPU, body composition and functional measures in healthy (50-65 years)
women. WBPU and functional measures were compared between women who routinely
practiced yoga (YOGA; n = 7) and nonactive counterparts (CON; n = 8). Q (0.61 +/-
0.06 vs. 0.78 +/- 0.07, p = .04), PS (3.07 +/- 0.37 vs. 4.17 +/- 0.40, p = .03),
PB (2.59 +/- 0.48 vs. 3.80 +/- 0.48, p = .05) were lower, and lean body mass
higher (64 +/- 1 vs. 58 +/- 2%, p <= .01) for YOGA vs. CON, respectively. WBPB
and functional measures were similar. Routine yoga practice influenced WBPU in
healthy older women. Study findings are novel and provide a basis for future
investigations evaluating long-term benefits of yoga as an alternative mode of
exercise for maintaining muscle mass in support of active aging.
PMID- 28422544
TI - Effects of Balance-Coordination, Strengthening, and Aerobic Exercises to Prevent
Falls in Postmenopausal Patients With Osteoporosis: A 6-Month Randomized Parallel
Prospective Study.
AB - Osteoporosis is a systemic disease characterized by the increase of bone
fragility and fracture risk. Postmenopausal female osteoporotic patients were
randomized into three groups: balance and coordination, strengthening, and
aerobic exercise. The exercise programs were performed for 12 weeks, 1 hr each
day for 3 days of the week. Patients were followed-up for 12 weeks after the
initial intervention. After the exercise program, patients continued their daily
life activities and were called back to the clinic for additional testing after
12 weeks. Static and dynamic balance measurements and pain and life quality
assessments were performed at enrollment, and at the 12th and 24th weeks.
Significant improvements in both the Timed Up and Go test and Berg Balance Scale
values at the 12th week were only observed in the balance-coordination group.
There were statistically significant improvements in night and daytime pain
visual analog scale scores at the 12th and 24th weeks in the strengthening
exercise group. No patient experienced falling during the 24th week follow-up.
The strengthening exercises were observed to be more effective in pain reduction,
and balance and coordination exercises were found to be more effective in
improvement of static and dynamic balance.
PMID- 28422543
TI - Newer Insights into the Antidiarrheal Effects of Acacia catechu Willd. Extract in
Guinea Pig.
AB - Acacia catechu Willd. is a plant diffused in India and other Asian countries,
where it is used as a traditional medicine for the treatment of several ailments
including diarrhea, one of the most common pathologies worldwide. In this study,
we determined the chemical composition of Acacia catechu Willd. extract (AC) and
evaluated its effect on spontaneous and induced contractility in isolated guinea
pig ileum and proximal colon. Preliminary data about its antimicrobial effect
against some pathogen agents versus some microbiota intestinal strain have been
also reported. Chemical analysis revealed the presence of catechins, such as (-)
Epicatechin and (+)-Catechin. AC extract reduced frequency and amplitude of colon
smooth muscle spontaneous contractility, in a concentration-dependent manner. A
weaker effect of the extract was exerted toward ileum smooth muscle spontaneous
contractility. The observed calcium antagonistic effect was more potent in
proximal colon than in ileum. The extract showed a noncompetitive reversible
antagonism to carbachol, both in proximal colon and ileum, with a higher potency
in proximal colon. The antimicrobial effects of AC extract were observed toward
Campylobacter jejuni, Escherichia coli, and Salmonella spp., while Bifido and
Lactobacillus were not affected by treatment. These effects, however, occurred at
concentrations fivefold higher than those inhibiting ileum and colon
contractility. In conclusion, our results suggest that AC affects intestinal
contractility without affecting intestinal bacterial flora and this may result in
clinical benefits in patients suffering from nonbacterial diarrhea.
PMID- 28422545
TI - Response to Aslankurt et al. re: "Safety Profile of Stromal Hydration of Clear
Corneal Incisions with Cefuroxime in the Mouse Model".
PMID- 28422546
TI - No Compromise of Competition Sleep Compared With Habitual Sleep in Elite
Australian Footballers.
AB - PURPOSE: To assess the impact of match-start time and days relative to match
compared with the habitual sleep characteristics of elite Australian Football
(AF) players. METHODS: 45 elite male AF players were assessed during the
preseason (habitual) and across 4 home matches during the season. Players wore an
activity monitor the night before (-1), night of (0), 1 night after (+1), and 2
nights (+2) after each match and completed a self-reported rating of sleep
quality. A 2-way ANOVA with Tukey post hoc was used to determine differences in
sleep characteristics between match-start times and days relative to the match.
Two-way nested ANOVA was conducted to examine differences between competition and
habitual phases. Effect size +/- 90% confidence interval (ES +/- 90% CI) was
calculated to quantify the magnitude of pairwise differences. RESULTS:
Differences observed in sleep-onset latency (ES = 0.11 +/- 0.16), sleep rating
(ES = 0.08 +/- 0.14), and sleep duration (ES = 0.08 +/- 0.01) between competition
and habitual periods were trivial. Sleep efficiency was almost certainly higher
during competition than habitual, but this was not reflected in the subjective
rating of sleep quality. CONCLUSIONS: Elite AF competition does not cause
substantial disruption to sleep characteristics compared with habitual sleep.
While match-start time has some impact on sleep variables, it appears that the
match itself is more of a disruption than the start time. Subjective ratings of
sleep from well-being questionnaires appear limited in their ability to
accurately provide an indication of sleep quality.
PMID- 28422547
TI - Active Travel Behavior in a Border Region of Texas and New Mexico: Motivators,
Deterrents, and Characteristics.
AB - BACKGROUND: Active travel has been linked with improved transportation and health
outcomes, such as reduced traffic congestion and air pollution, improved
mobility, accessibility, and equity, and increased physical and mental health.
The purpose of this study was to better understand active travel characteristics,
motivators, and deterrents in the El Paso, TX, region. METHODS: A multimodal
transportation survey brought together elements of transportation and health,
with a focus on attitudinal characteristics. The analysis consisted of an initial
descriptive analysis, spatial analysis, and multivariate binary and ordered
response models of walking and bicycling behavior. RESULTS: The motivators and
deterrents of active travel differed for walkers, bicyclists, and noncyclists
interested in bicycling. The link between active travel and life satisfaction was
moderated by age, with a negative association for older travelers. This effect
was stronger for bicycling than it was for walking. CONCLUSIONS: Based on the
findings, several interventions to encourage walking and bicycling were
suggested. These included infrastructure and built environment enhancements,
workplace programs, and interventions targeting specific subpopulations.
PMID- 28422548
TI - Epidemiological Profile and Treatment Outcomes in Young Adults (19-29 Years of
Age) Treated for Cancer in a Tertiary Hospital in Sao Paulo, Brazil.
AB - BACKGROUND: Worldwide, the incidence of cancer in young adults (20-39 years) is
increasing, and represents an important cause of mortality in this age group. A
retrospective study was undertaken to provide information that may lead to
improved treatment outcomes. METHODS: Epidemiological, clinicopathological,
treatment, and survival information were retrieved from the electronic database
registry of a tertiary referral hospital in Sao Paulo, Brazil for patients 19-29
years of age diagnosed with cancer between January 2007 and December 2012.
RESULTS: There were 960 patients with a median age at diagnosis of 26 years;
female patients comprised 59.2%. A previous diagnosis of malignancy was present
in 2.3%; 0.4% had malignant tumors that were radiation-associated; regular
alcohol use was present in 10.4%; 9% of patients reported tobacco use; a family
history of cancer was present in 41.7%. Malignant tumors included carcinomas
(45.7%), germ cell and trophoblastic neoplasms (12.3%), and lymphomas (12.1%).
Median follow-up was 47.7 months (range: 0.62-100.9 months) during which time 111
patients (13.5%) died. Carcinomas (n = 43, 38.7%), soft tissue sarcomas (n = 18,
16.2%), and leukemias (n = 10, 9.0%) were the most common causes of death.
CONCLUSIONS: This study has shown that carcinomas represent the most common
malignancy in adolescents and young adults referred to a tertiary cancer center
in Brazil and are the most common cause of mortality. Because clinical outcome
may be affected by multiple factors in this patient population, further global
studies are needed to characterize this population and improve clinical care.
PMID- 28422549
TI - Obesity is Associated With Altered Plantar Pressure Distribution in Older Women.
AB - Increased plantar pressure has been found to be related with greater risk of
falling. Although there is evidence suggesting that obesity is linked to foot
disorders, the association between obesity and plantar pressure of older adults
has been poorly investigated. The purpose of this study was to examine the
association between obesity and plantar pressure distribution and to explore its
relationship with body fat distribution. Two hundred and eleven older women took
part in this cross-sectional study. Body mass index was taken for obesity
classification. Whole body, android, and gynoid fat percentage was assessed using
dual-energy x-ray absorptiometry. Peak plantar pressure was evaluated during gait
using an Emed AT-4 pressure platform. Obese volunteers generated greater peak
pressure at midfoot (187.26 kPa) compared to both normal weight (128.52 kPa, p <
.001) and overweight (165.74 kPa, p < .001). Peak plantar pressure at midfoot was
also greater in overweight compared to normal weight (p < .001). At forefoot,
peak pressure was higher in the obese (498.15 kPa) compared to normal weight
volunteers (420.41 kPa, p = .007). Additionally, whole body, android, and gynoid
fat percentage were significantly associated with peak pressure at midfoot and
forefoot. Therefore, clinicians dealing with falls should consider the effect of
increased body weight on plantar pressure.
PMID- 28422550
TI - Evaluation of the diagnostic accuracy of UBC(r) Rapid in bladder cancer: a
Swedish multicentre study.
AB - OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of
UBC(r) Rapid - a urine-based marker for bladder cancer - in patients with bladder
cancer and controls, and to compare the test results across risk groups.
MATERIALS AND METHODS: This prospective phase II study was conducted at four
Swedish hospitals. UBC Rapid was evaluated in four groups: A, newly diagnosed
bladder cancer (n = 94); B, follow-up of non-muscle-invasive bladder cancer (n =
75); C, benign urinary tract diseases (n = 51); and D, healthy controls (n = 50).
Tumours were divided into high risk (carcinoma in situ, TaG3, T1, T2 and T3) and
low risk (low malignant potential, TaG1 and TaG2). Urine samples were
quantitatively analysed by UBC Rapid. Sensitivity, specificity, positive
predictive value (PPV) and negative predictive value (NPV) were calculated based
on optimal cut-off (receiver operator characteristics curve analysis). A linear
regression compared the UBC Rapid results in the different risk groups. RESULTS:
The optimal cut-off was 8.1 MUg/l. The median UBC Rapid values were 9.3 MUg/l
[interquartile range (IQR) 30.9] and 4.3 MUg/l (IQR 7.8) in patients with
positive and negative cystoscopy, respectively (p < .001). The value for group A
was 15.6 MUg/l (IQR 37.9), group B 5.6 MUg/l (IQR 8.6), group C 5.1 MUg/l (IQR
9.0) and group D 3.3 MUg/l (IQR 7.1). Sensitivity was 70.8%, specificity 61.4%,
PPV 71.3% and NPV 60.8%. The high-risk group had significantly higher UBC Rapid
values than the low-risk group: 20.5 MUg/l (IQR 42.2), sensitivity 79.2% and
specificity 61.4% versus 7.0 MUg/l (IQR 9.9), sensitivity 60.0% and specificity
61.4% (p = .039). CONCLUSIONS: The UBC Rapid urine-based marker for bladder
cancer gave higher values in patients with positive than in those with negative
cystoscopy. The diagnostic accuracy was better in patients with high-risk than in
those with low-risk tumours, and was better during primary detection than during
surveillance.
PMID- 28422551
TI - Estimation of Gait Independence Using a Tri-Axial Accelerometer in Stroke
Patients.
AB - The purpose of this study was to clarify whether a gait analysis using an
accelerometer could estimate gait independence. Eighty-six stroke patients and 21
healthy control subjects participated in this study. Stroke patients were
identified as dependent or independent based on their gait ability. The
acceleration of the trunk and bilateral thigh was measured using three wireless
sensors during walking. The root mean square, gait regularity, and symmetry were
calculated from the acceleration to estimate gait quality. ANCOVA showed that
gait regularity of the trunk and bilateral thigh were significantly lowest in the
dependent group, regardless of gait velocity. A logistic regression analysis
showed that the regularity and root mean square of the anteroposterior
acceleration of the unaffected thigh were the key factors for estimating gait
independence. This study suggests that an acceleration-based gait analysis
facilities gait independence estimation, and is a useful tool during the
rehabilitation of stroke patients.
PMID- 28422552
TI - Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy in Gilan
Province, Iran.
AB - PURPOSE: To conduct an assessment of avoidable blindness and diabetic retinopathy
(DR) in Gilan, 2014. METHODS: A cross-sectional population-based survey was
performed on a representative sample of urban and rural individuals aged >=50
years of the province. Blindness was defined as presenting visual acuity (PVA)
<3/60 in the better eye. Moderate visual impairment (MVI) and severe visual
impairment (SVI) were defined as 6/60 <= PVA <6/18 and 3/60 <= PVA <6/60 in the
better eye, respectively. Diabetes mellitus (DM) was determined based on random
blood sugar (RBS) levels >=200 mg/dL or a previous diagnosis. We used the
Scottish grading system to grade DR. RESULTS: We invited 2975 individuals from 85
clusters. Age- and sex-adjusted prevalence and 95% confidence interval (CI) of
blindness, SVI, MVI, and DM in 2587 participants (response rate: 86.9%) were 1.5%
(95% CI: 1.1-2.0), 1.5% (95% CI: 0.9-2.0), 11.3% (95% CI: 9.9-12.7) and 21.4%
(95% CI: 19.2-23.7), respectively. The leading causes of blindness were cataract
(47.1%), age-related macular degeneration (14.7%) and DR (8.8%). Cataract surgery
(CS) coverage was 69.3%. The main challenges for CS were cost and unawareness.
The outcome of CS was good in 66.9% of operated eyes. Any DR and/or maculopathy
were observed in 25.3% (95% CI: 21.0-29.5) of subjects including 12.6% (95% CI:
9.7-15.6) sight-threatening DR. In previously known DM cases, 215 (41.7%) had
never undergone an eye examination for DR. CONCLUSION: The proportion of
avoidable blindness and DR is considerable in Gilan Province.
PMID- 28422554
TI - Reply to J. Stenman et al.
PMID- 28422553
TI - Psychometric Properties of the Brazilian Portuguese Version of the PARmed-X for
Pregnancy.
AB - BACKGROUND: The Physical Activity Readiness Medical Examination (PARmed-X) for
Pregnancy aims to facilitate the communication between the health care provider,
the fitness professional and the pregnant woman. The purpose of the current study
was to test the psychometric properties of the Brazilian Portuguese version of
the PARmed-X for Pregnancy. METHODS: Reliability and validity of psychometric
properties of the Brazilian Portuguese version of the PARmed-X for Pregnancy were
tested in 107 women recruited from the Hospital de Clinicas de Porto Alegre.
Participants completed the first page of the instrument twice with a minimal
interval of 1 week for test-retest reliability analysis. The absolute and
relative contraindications to exercise on page 2 of the document were completed
by the obstetrician. RESULTS: Results indicated good evidence of construct
validity. The isolated items in the PARmed-X document presented a large
heterogeneity in kappa coefficients ranging from very low estimates to perfect
estimates. The overall indication of prescription of physical activity,
nonetheless, presented a good kappa coefficient of 0.749. CONCLUSIONS: The
Brazilian Portuguese version of the PARmed-X for Pregnancy can be applied as a
valid tool for medical screening by health care providers to help inform safe
exercise prescription during pregnancy.
PMID- 28422555
TI - Improved Local Control by Extensive Surgery in High-Risk Neuroblastoma May Be
Dependent on Adjuvant Radiotherapy.
PMID- 28422556
TI - The Acute Effects of Breaking Up Seated Office Work With Standing or Light
Intensity Walking on Interstitial Glucose Concentration: A Randomized Crossover
Trial.
AB - BACKGROUND: The aim of this randomized, 3-period, 3-treatment crossover trial was
to examine the acute effects of regularly breaking up seated office work with
short bouts of standing or light-intensity walking on postprandial interstitial
glucose concentration. METHODS: Seventeen middle-aged office workers performed 3
5-hour trial conditions at their workplace in a random order: 1) uninterrupted
sitting, 2) sitting interrupted by 2 minutes of standing every 20 minutes, and 3)
sitting interrupted by 2 minutes of light-intensity walking every 20 minutes.
Participants consumed 2 standardized test drinks at the start of each trial
condition and an iPro2 continuous glucose monitoring system (CGMS) recorded
average interstitial glucose concentration every 5 minutes for the duration of
the study. RESULTS: The 5-hour interstitial glucose incremental area under the
curve (iAUC) was 55.5% lower after sitting interrupted by light-intensity walking
compared with after uninterrupted sitting (95% CI, -104.2% to -6.8%). There was
also a suggestion of a beneficial effect of regular standing breaks, particularly
in overweight men, although they were not as effective as the walking breaks
(mean difference [95% CI], -29.6% [-73.9% to 14.7%]). CONCLUSIONS: Regularly
breaking up prolonged sitting lowers postprandial glycemia in middle-aged adults
without metabolic impairment.
PMID- 28422557
TI - Maximal Aerobic Power in Aging Men: Insights From a Record of 1-Hour
Unaccompanied Cycling.
AB - PURPOSE: To analyze best 1-h unaccompanied performances of master athletes in
ages ranging from 35 to 105 y to estimate the decay of maximal aerobic power
(MAP) across the spectrum of age. METHODS: MAP at the various ages was estimated
by computing the metabolic power ([Formula: see text]) maintained to cover the
distances during best 1-h unaccompanied performances established by master
athletes of different classes of age and by assuming that they were able to
maintain an [Formula: see text] equal to 88% of their MAP during 1 h of
exhaustive exercise. RESULTS: MAP started monotonically decreasing at 47 y of
age. Thereafter, it showed an average rate of decrease of ~14% for the decades up
to 105 y of age, similar to other classes of master athletes. CONCLUSIONS: The
results confirm, by extending the analysis to centennial subjects, that MAP seems
to start declining from the middle of the 5th decade of age, with an average
percentage decay that is faster than that traditionally reported, even when one
maintains a very active lifestyle. The proposed approach may be applied to other
types of human locomotion for which the relationship between speed and [Formula:
see text] is known.
PMID- 28422558
TI - Understanding Transgender Men's Experiences with and Preferences for Cervical
Cancer Screening: A Rapid Assessment Survey.
AB - PURPOSE: Transgender men are less likely than cisgender women to receive cervical
cancer screening. The purpose of the current study was to understand experiences
with and preferences for cervical cancer screening among transgender men.
METHODS: Ninety-one transgender men ages 21-63 completed the survey. The survey
evaluated experiences with and preferences for screening, including opinions
regarding human papillomavirus (HPV) self-sampling as a primary cervical cancer
screening. RESULTS: Half (50.5%) of participants did not have Pap smear screening
within the past 3 years. The majority (57.1%) of participants preferred HPV self
sampling over provider-collected Pap smear screening. Participants who reported
discrimination were more likely to prefer HPV self-sampling (odds ratio = 3.29,
95% confidence interval 1.38-7.84, P = 0.007). CONCLUSION: Primary HPV testing
via HPV self-sampling may improve cervical cancer screening uptake among
transgender men. Future work should pilot this innovative cervical cancer
screening method within this population.
PMID- 28422559
TI - The Influence of Ambulatory Aid on Lower-Extremity Muscle Activation During Gait.
AB - CONTEXT: Foot and ankle injuries are common and often require a nonweight-bearing
period of immobilization for the involved leg. This nonweight-bearing period
usually results in muscle atrophy for the involved leg. There is a dearth of
objective data describing muscle activation for different ambulatory aids that
are used during the aforementioned nonweight-bearing period. OBJECTIVE: To
compare activation amplitudes for 4 leg muscles during (1) able-bodied gait and
(2) ambulation involving 3 different ambulatory aids that can be used during the
acute phase of foot and ankle injury care. DESIGN: Within-subject, repeated
measures. SETTING: University biomechanics laboratory. PARTICIPANTS: Sixteen able
bodied individuals (7 females and 9 males). INTERVENTION: Each participant
performed able-bodied gait and ambulation using 3 different ambulatory aids
(traditional axillary crutches, knee scooter, and a novel lower-leg prosthesis).
MAIN OUTCOME MEASURE: Muscle activation amplitude quantified via mean surface
electromyography amplitude throughout the stance phase of ambulation. RESULTS:
Numerous statistical differences (P < .05) existed for muscle activation
amplitude between the 4 observed muscles, 3 ambulatory aids, and able-bodied
gait. For the involved leg, comparing the 3 ambulatory aids: (1) knee scooter
ambulation resulted in the greatest vastus lateralis activation, (2) ambulation
using the novel prosthesis and traditional crutches resulted in greater biceps
femoris activation than knee scooter ambulation, and (3) ambulation using the
novel prosthesis resulted in the greatest gastrocnemius activation (P < .05).
Generally speaking, muscle activation amplitudes were most similar to able-bodied
gait when subjects were ambulating using the knee scooter or novel prosthesis.
CONCLUSIONS: Type of ambulatory aid influences muscle activation amplitude.
Traditional axillary crutches appear to be less likely to mitigate muscle atrophy
during the nonweighting, immobilization period that often follows foot or ankle
injuries. Researchers and clinicians should consider these results when
recommending ambulatory aids for foot or ankle injuries.
PMID- 28422560
TI - Effect of Physical Activity Intervention in Prediabetes: A Systematic Review With
Meta-analysis.
AB - BACKGROUND: Prediabetes is a strong risk factor for the development of Type2
Diabetes Mellitus (T2DM). Modification in lifestyle plays an important role to
avoid the prognosis of T2DM and its complications in future. The aim of our study
was to focus on the effectiveness of physical activity (PA) intervention program
on different outcome measures in individuals with prediabetes. The effort of the
present review was to contribute to the existing literature by strengthening the
evidence pointing toward the positive impact of physical activity in individuals
with prediabetes. METHODS: Studies have been identified through database like
PubMed, Scopus, and ProQuest. Randomized and nonrandomized controlled trials have
been included. Nineteen articles have been selected for the qualitative analysis
and 08 for meta-analysis. RESULTS: PA intervention showed a favorable effect on
improving oral glucose tolerance (Risk ratio [RR] -0.26, 95% CI -0.06 to 0.07)
and fasting blood sugar (RR -0.05, 95% CI -0.14 to 0.04). It also showed the
favorable effect on glycated hemoglobin (HbA1C), maximum oxygen uptake (VO2max),
and body composition. CONCLUSION: Present review suggests that the PA promotion
and participation can help to slow down the progression of disease in individuals
with prediabetes and thus reduces the morbidity and mortality associated with
T2DM.
PMID- 28422561
TI - Development and Feasibility of a Structured Goals of Care Communication Guide.
AB - BACKGROUND: Discussing goals of care and advance care planning is beneficial, yet
how to best integrate goals of care communication into clinical care remains
unclear. OBJECTIVE: To develop and determine the feasibility of a structured
goals of care communication guide for nurses and social workers.
DESIGN/SETTING/SUBJECTS: Developmental study with providers in an academic and
Veterans Affairs (VA) health system (n = 42) and subsequent pilot testing with
patients with chronic obstructive pulmonary disease or heart failure (n = 15) and
informal caregivers (n = 4) in a VA health system. During pilot testing, the
communication guide was administered, followed by semistructured, open-ended
questions about the content and process of communication. Changes to the guide
were made iteratively, and subsequent piloting occurred until no additional
changes emerged. MEASUREMENTS: Provider and patient feedback to the communication
guide. RESULTS: Iterative input resulted in the goals of care communication
guide. The guide included questions to elicit patient understanding of and
attitudes toward the future of illness, clarify values and goals, identify end-of
life preferences, and agree on a follow-up plan. Revisions to guide content and
phrasing continued during development and pilot testing. In pilot testing,
patients validated the importance of the topic; none said the goals of care
discussion should not be conducted. Patients and informal caregivers liked the
final guide length (~30 minutes), felt it flowed well, and was clear.
CONCLUSIONS: In this developmental and pilot study, a structured goals of care
communication guide was iteratively designed, implemented by nurses and social
workers, and was feasible based on administration time and acceptability by
patients and providers.
PMID- 28422562
TI - From Perception to Action: The Mediating Role of Parental Safety Concerns on
Adolescents' Physical Activity.
AB - BACKGROUND: Parental safety concerns have been recognized as a critical
determinant of adolescents' physical activity. However, it is still uncertain
what factors relate to parental safety concern, and how they, in turn, affect
adolescents' physical activity. This study explored the mediating relationships
of parental safety concern on adolescents' physical activity by considering
personal, social, and built environmental factors. METHODS: This cross-sectional
analysis used the data from Growing Up in Ireland (GUI), a national study (N =
5212). A structural equation model (SEM) was used to evaluate the hypothesized
framework. RESULTS: 50% of the adolescents engaged in at least 6 days of exercise
every 14 days, at a rate of at least 20-minutes per day. Adolescents were more
physically active when parents perceived higher levels of safety. Parents
perceived their children as safe when they lived in areas with easy access to
play spaces. Moreover, adolescents with more close friends and more friends with
whom they could play were more physically active and their parents perceived
higher levels of safety. CONCLUSIONS: Parental safety concerns may profoundly
affect adolescent's physical activity and the resulting health outcomes. Programs
and policies should consider the importance of parental safety concerns in
promoting adolescents' physical activity.
PMID- 28422563
TI - Effects of Anterior Knee Displacement During Squatting on Patellofemoral Joint
Stress.
AB - CONTEXT: Squatting is a common rehabilitation training exercise for
patellofemoral pain syndrome (PFPS). Patellofemoral joint stress (PFJS) during
squatting with more anterior knee displacement has not been systematically
investigated. OBJECTIVE: To compare PFJS during squatting using 2 techniques:
squat while keeping the knees behind the toes (SBT) and squat while allowing the
knees to go past the toes (SPT). SETTING: University research laboratory.
PARTICIPANTS: Twenty-five healthy females (age: 22.69 (0.74) y; height: 169.39
(6.44) cm; mass: 61.55 (9.74) kg) participated. MAIN OUTCOME MEASURES: Three
dimensional kinematic and kinetic data were collected at 180 and 1800 Hz,
respectively. A musculoskeletal model was used to calculate muscle forces through
static optimization. These muscle forces were used in a patellofemoral joint
model to estimate PFJS. RESULTS: The magnitudes of PFJS, reaction force, and
quadriceps force were higher (P < .001) during SPT compared with the SBT
technique. Knee flexion, hip flexion, and ankle dorsiflexion angles were reduced
when using the SBT technique. CONCLUSIONS: Findings provide some general support
for minimizing forward knee translation during squats for patients that may have
patellofemoral pain syndrome.
PMID- 28422564
TI - Evaluation of two in-house immunoenzymatic tests to serodiagnose subclinical
paratuberculisis in a sheep flock in Mexicali valley, Mexico.
AB - Paratuberculosis (PTB) or Johne's disease is a common ruminant infectious disease
caused by Mycobacterium avium subsp. paratuberculosis (MAP). In this study, two
MAP antigens were compared for their diagnostic utility to detect subclinical PTB
in a sheep flock in Mexicali, Mexico. Sheep (n = 31) without clinical signs but
positive on a direct fecal-polymerase chain reaction were tested with two
preabsorbed in-house enzyme linked immunosorbent assays (ELISAs) using: (1) an
ethanol-extracted surface lipid antigen (EVELISA) and (2) a protoplasmic antigen
(ELISA-PPA). Sensitivities of the EVELISA and ELISA-PPA were 84% (95% CI; 66-95%)
and 29% (95% CI; 14-48%), respectively. The EVELISA test could be a fast and
effective way to identify subclinical ovine PTB for severely affected flocks.
PMID- 28422565
TI - Ascorbic acid deficiency in patients with lichen planus.
AB - OBJECTIVES: Recent studies have highlighted the role of oxidative stress in the
pathogenesis of lichen planus (LP). In the present study, the interest of the
authors is focused on the investigation of ascorbic acid status in patients with
LP and identification of parameters that might influence the level of this
vitamin. MATERIAL AND METHOD: We analyzed the level of urinary ascorbic acid
(reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral
LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants
included clinical examination and laboratory and imaging tests. RESULTS: Compared
to the control group (19.82 mg/dl) the level of ascorbic acid was significantly
lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP
(8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of
ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary
concentrations of ascorbic acid were significantly lower in patients with LP
associated with infections compared to patients with LP without infections.
CONCLUSIONS: The urinary ascorbic acid level may be a useful parameter in
identifying patients with LP who are at risk of developing viral or bacterial
infections.
PMID- 28422566
TI - Content uniformity testing for stratified samples via parametric tolerance
interval testing.
AB - Historically in the biopharmaceutical setting, USP<905> has been used to
establish that a batch of drug product has acceptable content uniformity. More
recently, alternative approaches such as the two one-sided parametric tolerance
interval test (PTI-TOST) have been proposed to establish content uniformity.
Traditionally, the PTI-TOST is implemented as a sequential, two-tiered test,
under the generally accepted assumption that the data are independently and
identically distributed. Since the material is sequenced through the
manufacturing process over a period of time, there are conceptually arguable
locations within each batch, for instance: beginning, middle, and end. In such a
situation, a practitioner may wish to evaluate potential effects of these batch
locations, for example, during process validation. If location (stratified)
differences exist within the batch and if multiple samples are taken from each
location, significant within-location correlations may be induced in the data. In
such a case, the traditional PTI-TOST underestimates the total variability,
thereby improperly boosting the power of the test method. When there is reason to
believe that location variances exist, the batch may be evaluated using
stratified sampling, and the location effect may be modeled. In this paper, a two
tiered PTI-TOST that accounts for both between-location and within-location
variance components is introduced. Operating characteristic curves and practical
advice are given to aid the practitioner's uptake of the proposed method.
PMID- 28422567
TI - Evaluation of serotypes 5 and 8 capsular polysaccharides in protection against
Staphylococcus aureus in murine models of infection.
AB - Staphylococcus aureus is the leading cause of nosocomial and community-acquired
infections, including soft tissue and skin infections and bacteremia. However,
efforts to develop an effective vaccine against S. aureus infections have not
been successful. We evaluated serotypes 5 and 8 capsule polysaccharides (CP)
CRM197 conjugates as vaccine candidates in murine models of bacteremia, lethal
sepsis, and skin infection. The conjugate vaccines elicited a good antibody
response, and active immunization of CP5-CRM or CP8-CRM conjugates protected
against staphylococcal bacteremia. In the skin infection model, CP8-CRM but not
CP5-CRM protected against dermonecrosis, and CP8-CRM immunization significantly
decreased the bacterial burden in the lesion. However, neither CP5-CRM nor CP8
CRM protected against mortality in the lethal sepsis model. The results indicate
the capsular vaccines elicit protection against some, but not all, aspects of
staphylococcal infection.
PMID- 28422569
TI - Preparation of a novel antibacterial chitosan-poly(ethylene glycol)
cryogel/silver nanoparticles composites.
AB - Cryogel was synthesized through cryogelation of methacrylated carboxymethyl
chitosan (mCMC) and poly(ethylene glycol) diacrylate (PEGDA) precursors by
photopolymerization. Due to its excellent properties, such as fast swelling
behavior, inter-connective porous structure, high water absorbing capacity,
especially the presence of abundant carboxylmethyl groups on its backbone, the
cryogel not only favored the absorption of silver ions but also was proved to be
a good matrix for the incorporation of silver nanoparticles (AgNPs) by in situ
chemical reduction. The structure, morphology, and swelling behavior of the
cryogel and cryogel/AgNPs composite were characterized. And the results of
inhibition zone test and antibacterial inhibition ratio indicated the
cryogel/AgNPs composite exhibited prominent and durable antibacterial activity
against Gram-negative E. coli and could be utilized as potential antibacterial
materials.
PMID- 28422568
TI - cGAS-STING-TBK1-IRF3/7 induced interferon-beta contributes to the clearing of non
tuberculous mycobacterial infection in mice.
AB - Type I interferons (IFN-I), such as IFN-alpha and IFN-beta are important
messengers in the host response against bacterial infections. Knowledge about the
role of IFN-I in infections by nontuberculous mycobacteria (NTM) is limited. Here
we show that macrophages infected with pathogens of the Mycobacterium avium
complex produced significantly lower amounts of IFN-beta than macrophages
infected with the opportunistic pathogen M. smegmatis. To dissect the molecular
mechanisms of this phenomenon, we focused on the obligate pathogen Mycobacterium
avium ssp paratuberculosis (MAP) and the opportunistic M. smegmatis. Viability of
both bacteria was required for induction of IFN-beta in macrophages. Both
bacteria induced IFN-beta via the cGAS-STING-TBK1-IRF3/7-pathway of IFN-beta
activation. Stronger phosphorylation of TBK1 and higher amounts of extracellular
bacterial DNA in the macrophage cytosol were found in M. smegmatis infected
macrophages than in MAP infected macrophages. After intraperitoneal infection of
mice, a strong Ifnb induction by M. smegmatis correlated with clearance of the
bacteria. In contrast, MAP only induced weak Ifnb expression which correlated
with bacterial persistence and increased number of granulomas in the liver. In
mice lacking the type I interferon receptor we observed improved survival of M.
smegmatis while survival of MAP was similar to that in wildtype mice. On the
other hand, treatment of MAP infected wildtype mice with the IFN-I inducer
poly(I:C) or recombinant IFN-beta impaired the survival of MAP. This indicates an
essential role of IFN-I in clearing infections by MAP and M. smegmatis. The
expression level of IFN-I is decisive for transient versus persistent NTM
infection.
PMID- 28422570
TI - An Induced Adipocyte Sheet Reduces Inflammatory Reactions During Remodeling of
Xenogeneic Scaffolds In Vivo.
AB - Surgical therapy of cardiovascular diseases frequently requires replacement of
diseased tissues with prosthetic devices or grafts. Calcification is the main
reason for the degeneration of implanted grafts. However, some factors reduce
stenosis and attenuate calcification of implanted grafts. In this study, we used
an autologous induced adipocyte cell-sheet (IACS) as a drug delivery system to
determine whether its secretion ability has a beneficial effect on the remodeling
process of grafts in a rat subcutaneous model. IACSs were generated from rat
adipose tissue-derived cells that secreted abundant adiponectin (APN), hepatocyte
growth factor, and vascular endothelial growth factor in vitro. Two types of
grafts were used in the rat subcutaneous model: decellularized and IACS-wrapped
decellularized porcine vascular grafts. Transplanted IACSs secreted APN into the
decellularized porcine vascular graft in rats at 4 weeks. After explanting from
the rat subcutaneous model at 1, 2, 4, and 8 weeks, immunofluorescence staining
showed that IACS-wrapped grafts had a dominant M2 phenotype of macrophages (p <
0.001) at all time points and showed constructive remodeling and less
calcification at 8 weeks. The decellularized graft showed a predominately CCR7+
cell response (M1 phenotype) (p < 0.001) and was characterized by chronic
inflammation and severe calcification at 8 weeks. Furthermore, the IACS-wrapped
side of the graft showed less cell infiltration compared with the other side,
which may have reduced inflammation in the area. Transplantation of IACSs with a
biological scaffold had a profound influence on the macrophage phenotype and
downstream remodeling processes. The method might reduce inflammatory reactions
during remodeling of xenogeneic scaffolds and result in less calcification.
PMID- 28422571
TI - Reliability of Measuring Lower-Limb-Muscle Electromyography Activity Ratio in
Activities of Daily Living With Electrodes Embedded in the Clothing.
AB - CONTEXT: Using technical clothes with electrodes embedded in the clothing makes
it possible to record the electrical activity produced by the activity of the
skeletal muscles in activities of daily living. OBJECTIVE: To investigate the
reliability of measuring lower-limb left-right electromyography (EMG) activity
ratio with smart shorts during stair descent, stair ascent, and repeated unloaded
squats among healthy working-aged subjects. METHODS: Seventeen females (mean age
25.5 y), and 17 males (mean age 29.9 y) participated in this test-retest protocol
carried out twice on the same day. RESULTS: Intraclass correlation coefficient
(ICC) varied from .65 to .80 in the different activities. Mean difference and
limits of agreement (LOA) between the repeated measurements were for descending
stairs -0.8%, LOA -6.2% to 4.7%; for ascending stairs -0.9%, -6.5% to 4.7%; and
for squats -0.2%, -5.4% to 4.9%. The coefficient of repeatability for descending
stairs was 5.6%, for ascending stairs 5.7%, and for squats 5.3%. CONCLUSIONS: Our
study among healthy subjects showed that the left-right EMG activity ratio in
activities of daily living can be reliably measured with smart shorts. In future
research, the feasibility of technical clothes as a follow-up method in
rehabilitation should be investigated in greater detail.
PMID- 28422572
TI - Effect of Comprehensive School Physical Activity Programming on Cardiometabolic
Health Markers in Children From Low-Income Schools.
AB - BACKGROUND: The purpose of this study was to examine the effect of a 36-week
Comprehensive School Physical Activity Program (CSPAP) on cardiometabolic health
markers in children from low-income schools. METHODS: Participants were 217
school-aged children (mean age = 10.1 +/- 1.1 years; 114 girls, 103 boys)
recruited from 5 low-income elementary schools. Cardiometabolic health markers
were collected in a fasted state at 2 time-points, before commencement of the
CSPAP for classroom and school level clustering and the modifying effects of
grade level and sex, there were statistically significant improvements in HDL
cholesterol (Delta = 3.6 mg/dL, 95% CI: 1.4 mg/dL to 5.8 mg/dL, P = .039),
triglycerides (Delta = -14.1 mg/dL, 95% CI: -21.4 mg/dL to -6.8 mg/dL, P = .022),
and mean arterial pressure (Delta = -4.3 mmHg, 95% CI: -8.5 mmHg to -0.1 mmHg, P
= .041) following the 36-week CSPAP intervention. Sixth-grade children showed
decreases in LDL cholesterol (Delta = -15.3 mg/dL, 95% CI: -30.5 mg/dL to -0.1
mg/dL, P = .033). CONCLUSIONS: Improvements in specific cardiometabolic health
markers were found following a 36-week CSPAP in children from low-income schools.
PMID- 28422573
TI - Results From the First French Report Card on Physical Activity for Children and
Adolescents.
AB - BACKGROUND: Many countries publish periodic Report Cards on physical activity for
children and youth. This paper presents the results from the first French Report
Card providing a systematic synthesis and assessment of the national engagements
to facilitate childhood physical activity. METHODS: A search for nationally
representative data on 8 indicators of physical activity was conducted and the
data were assessed by an expert panel according to international procedures.
Whether children across France are achieving specific benchmarks was rated using
an established grading framework [A, B, C, D, F, or INC (incomplete)]. Data were
interpreted, grades assigned and detailed in the 2016 Report Card that was
produced and disseminated. RESULTS: The expert panel awarded the following
grades: Overall Physical Activity: INC; Organized Sport Participation: D; Active
Transportation: D; Sedentary Behaviors: D; Family and Peers: INC; School: B;
Community and the Built Environment: INC; Government Strategies and Investment:
INC. CONCLUSIONS: The grades reveal that efforts must be done to improve youth's
physical activity and that several gaps in the literature still need to be
addressed. Collectively the results highlight that children's physical activity
levels are low and that further national supports and investments are needed to
promote childhood healthy active living in France.
PMID- 28422574
TI - Social-Cognitive and Social-Behavioral Correlates of Suicide Risk in College
Students: Contributions from Interpersonal Theories of Suicide and Depression.
AB - Joiner's interpersonal-psychological theory of suicide (IPTS) is predated by
literature examining maladaptive interpersonal behaviors associated with
depression; however, research has not examined the potential relevance of such
behaviors for the IPTS. The current study aimed to expand understanding of
suicide risk by examining two maladaptive interpersonal behaviors in the context
of Joiner's IPTS model. Structural equation modeling examined associations
between depressive symptoms, social-cognitive predictors of suicide, maladaptive
interpersonal behaviors, and suicide risk in 228 college students (53.9% female;
M = 19.5 years, SD = 1.8). Social-cognitive IPTS variables mediated the relation
between depressive symptoms and maladaptive interpersonal behavior. Both social
cognition and maladaptive interpersonal behavior mediated the effect of
depressive symptoms on suicide risk. Findings have the potential to add to our
understanding of the interplay of social-cognitive factors and interpersonal
behaviors associated with suicide risk. Directions for future research are
discussed.
PMID- 28422575
TI - Cardiovascular Risk Factors of Long-Term Care Workers.
AB - Little is known about long-term care workers' cardiovascular disease (CVD) risk.
Thus, the authors used baseline objective and subjective data from 98 long-term
care staff participating in a worksite health promotion study to provide a
comprehensive CVD assessment. The median age of the sample was 32 years ( SD =
13.38). Nine (12.2%) participants smoked and 27 (37.0%) participants reported
exposure to secondhand smoke. The average nightly hours of sleep was 6.5 ( SD =
1.18), with 24 (32%) participants reporting sleeping at least fairly bad. Sixty
eight participants (73.1%) were overweight or obese. The median aerobic activity
was 0 ( SD = 18.56). Participants ate on average 27 ( SD = 17.34) servings of
high fatty and/or salty foods per week. Although blood pressure and cholesterol
levels were within normal limits, this population demonstrated poor behavioral
CVD risk factors. Given this finding and the young age of the sample, these
workers may be ideal candidates for health promotion efforts before health risk
factors are present.
PMID- 28422576
TI - Mechanisms of Action Contributing to Reductions in Suicide Attempts Following
Brief Cognitive Behavioral Therapy for Military Personnel: A Test of the
Interpersonal-Psychological Theory of Suicide.
AB - Brief cognitive behavioral therapy (BCBT) is associated with significant
reductions in suicide attempts among military personnel. However, the underlying
mechanisms of action contributing to reductions in suicide attempts in effective
psychological treatments remain largely unknown. The present study conducted a
secondary analysis of a randomized controlled trial of BCBT versus treatment as
usual (TAU) to examine the mechanisms of action hypothesized by the interpersonal
psychological theory of suicide (IPT): perceived burdensomeness, thwarted
belongingness, and fearlessness about death. In a sample of 152 active duty U.S.
Army personnel with recent suicide ideation or attempts, there were significantly
fewer suicide attempts in BCBT, but there were no differences between treatment
groups from baseline to 6 months postbaseline on any of the 3 IPT constructs or
their interactions. Tests of the moderated mediation failed to support an
indirect effect for the IPT model, regardless of which IPT variables were
specified as mediators or moderators. Results suggest that the IPT's hypothesized
mechanisms of action do not account for reductions in suicide attempts in BCBT.
Implications for clinical practice and research are discussed.
PMID- 28422577
TI - Enrichment of Zebrafish Danio rerio (Hamilton, 1822) Diet with Polyunsaturated
Fatty Acids Improves Fecundity and Larvae Quality.
AB - The zebrafish is a freshwater fish of the Cyprinidae family, which is frequently
used in scientific research. It owes its popularity to its genome, whose
structure is comparable to the human genome and, for this reason, this species is
often used in human medical research. However, such research requires high
quality material to conduct tests producing repeatable results. This study
examines the effect of providing feed enriched with essential fatty acids,
especially docosahexaenoic acid, to zebrafish spawners on fertility as well as
the survival rate and growth of their offspring. The experiments revealed a
significant (p < 0.05) effect of feeding spawners with feed enriched with
polyunsaturated fatty acids on all tested parameters: their fertility (30% higher
compared to the control group), survival rate, and the posthatching size of
larvae, which were larger by 13% and 4%, respectively, compared to the control
group.
PMID- 28422578
TI - Korean Version of the Mini-Mental State Examination Using Smartphone: A
Validation Study.
AB - BACKGROUND: Stroke often leads to disability, and poststroke survivors often have
limited accessibility to medical facilities. INTRODUCTION: For such patients,
mobile videoconferencing technology offers an opportunity to perform follow-up
assessment and appropriate management of cognitive impairment. We aimed to
determine the validity of the Korean version of the Mini-Mental State Examination
(MMSE-K) when administered using a smartphone. MATERIALS AND METHODS: Thirty
patients with ischemic or hemorrhagic stroke were included in this study (20
males, 10 females; mean age, 69.8 +/- 12.9 years). Both face-to-face and remote
assessments of cognitive function through MMSE-K were performed for each patient
at an interval of at least 3 days. Additionally, an in-person collaborator
evaluated the MMSE-K score during the remote assessment. A smartphone and a
tablet were used by the patient and the examiner, respectively, and remote
connection was mediated using a dedicated videoconferencing application. The MMSE
K scores obtained through face-to-face, remote, and in-person assessments were
compared using the Wilcoxon signed rank test and the Spearman correlation
analysis. RESULTS: There was good agreement between face-to-face and remote
assessments, as well as between remote assessment and in-person collaborator's
evaluation regarding total MMSE-K score and subscores for each MMSE-K domain
(orientation, memory, attention/calculation, language, and visuospatial
function). DISCUSSION: Remote assessment can be a useful clinical evaluation
method, and this study confirmed the validity. CONCLUSIONS: The smartphone
represents a promising tool for the assessment of cognitive function in clinical
practice, but further research into the intra- and inter-rater reliability of
observations is warranted.
PMID- 28422579
TI - Is the Higher Number of Suicide Attempts in Bipolar Disorder vs. Major Depressive
Disorder Attributable to Illness Severity?
AB - The present study represents an early stage investigation into the phenomenon
whereby those with bipolar disorder attempt suicide more frequently than those
with unipolar depression, but do not tend to attempt suicide during mania. Data
for this study were obtained from baseline measurements collected in a randomized
treatment study at a major southwestern United States military medical center. We
demonstrated the rarity of suicide attempts during mania, the higher frequency of
suicide attempts in those with bipolar disorder compared to those with
depression, and the persistence of effects after accounting for severity of
illness. These results provide the impetus for the development and testing of
theoretical explanations.
PMID- 28422580
TI - Glyphosate and Paraquat in Maternal and Fetal Serums in Thai Women.
AB - OBJECTIVES: This longitudinal study measured the glyphosate and paraquat
concentrations found in maternal and umbilical cord serum in 82 pregnant women
who gave birth in three provinces of Thailand. METHODS: Through questionnaires
and biological samples collected at childbirth, factors such as personal
characteristics, family members occupation, agricultural activities, and
herbicide use in agricultural work were evaluated as predictors of glyphosate and
paraquat levels in the pregnant women. Statistical analysis used univariate and
binary multiple logistic regression, where the outcome was the probability of
exposure to paraquat or glyphosate above the limit of detection associated with
occupation and household factors. RESULTS: The glyphosate concentrations in the
pregnant women's serum at childbirth (median: 17.5, range: 0.2-189.1 ng/mL) were
significantly higher (P < .007) than those in the umbilical cord serum (median:
0.2, range: 0.2-94.9 ng/mL). However, the paraquat concentrations in the serum of
the pregnant women at childbirth (83% <=limit of detection [LOD], with maximum of
58.3 ng/mL) were similar to those in the umbilical cord serum (80% LOD in serum at childbirth
were 11.9 times more likely to report work as an agriculturist (P < .001), 3.7
times more likely to live near agricultural areas (P = .006), and 5.9 times more
likely to have a family member who worked in agriculture (P < .001). The only
factors affecting paraquat exposures in pregnant women at childbirth were
reporting the agricultural activity of digging in farm soil and working in the
agricultural fields in the third trimester of pregnancy. CONCLUSIONS: These
results show that pregnant women who work in agriculture or live in families that
work in agriculture have higher exposures to the herbicides glyphosate and
paraquat. The potential for long-term health impacts of these prenatal exposures
to children should be evaluated, and greater regulation of the sale and use of
herbicides should be considered in Thailand.
PMID- 28422581
TI - "Straight from the heavens into your bucket": domestic rainwater harvesting as a
measure to improve water security in a subarctic indigenous community.
AB - BACKGROUND: Black Tickle-Domino is an extremely water-insecure remote Inuit
community in the Canadian subarctic that lacks piped-water. Drinking water
consumption in the community is less than a third of the Canadian national
average. Water insecurity in the community contributes to adverse health,
economic, and social effects and requires urgent action. OBJECTIVES: To test the
ability of domestic rainwater harvesting (DRWH) for the first time in the
subarctic with the goal of improving water access and use in the community.
DESIGN: This project utilised quantitative weekly reporting of water collection
and use, as well as focus group discussions. DRWH units were installed at seven
water-insecure households chosen by the local government. Results were measured
over a 6-week period in 2016. RESULTS: Participants harvested 19.07 gallons of
rainwater per week. General purpose water consumption increased by 17% and water
retrieval efforts declined by 40.92%. Households saved $12.70 CDN per week.
Participants reported perceived improvements to psychological health. Because no
potable water was collected, drinking water consumption did not increase. The
study identified additional water-insecurity impacts. CONCLUSION: DRWH cannot
supply drinking water without proper treatment and filtration; however, it can be
a partial remedy to water insecurity in the subarctic. DRWH is appropriately
scaled, inexpensive, and participants identified several significant benefits.
PMID- 28422582
TI - Combining Activity-Related Behaviors and Attributes Improves Prediction of Health
Status in NHANES.
AB - BACKGROUND: This paper tested whether a physical activity index (PAI) that
integrates PA-related behaviors (ie, moderate-to-vigorous physical activity
[MVPA] and TV viewing) and performance measures (ie, cardiorespiratory fitness
and muscle strength) improves prediction of health status. METHODS: Participants
were a nationally representative sample of US adults from 2011 to 2012 NHANES.
Dependent variables (self-reported health status, multimorbidity, functional
limitations, and metabolic syndrome) were dichotomized. Wald-F tests tested
whether the model with all PAI components had statistically significantly higher
area under the curve (AUC) values than the models with behavior or performance
scores alone, adjusting for covariates and complex survey design. RESULTS: The
AUC (95% CI) for PAI in relation to health status was 0.72 (0.68, 0.76), and PAI
AUC for multimorbidity was 0.72 (0.69, 0.75), which were significantly higher
than the behavior or performance scores alone. For functional limitations, the
PAI AUC was 0.71 (0.67, 0.74), significantly higher than performance, but not
behavior scores, while the PAI AUC for metabolic syndrome was 0.69 (0.66, 0.73),
higher than behavior but not performance scores. CONCLUSIONS: These results
provide empirical support that an integrated PAI may improve prediction of health
and disease. Future research should examine the clinical utility of a PAI and
verify these findings in prospective studies.
PMID- 28422583
TI - Altering the Speed Profiles of Wheelchair Rugby Players With Game-Simulation
Drill Design.
AB - PURPOSE: To examine the speed profiles of elite wheelchair rugby (WCR) players
during game-simulation training drills of differing player number and shot-clock
regulations. A secondary aim was to determine whether the profiles were further
influenced by player classification. METHODS: Eight elite WCR players (low-point
n = 3, high-point n = 5) were monitored using a radio-frequency-based indoor
tracking system during training sessions over a 5-mo period. Speed profiles were
collected for 3 modified game-simulation drills-3-versus-3 drills (n = 8
observations), 30-s shot clock (n = 24 observations), and 15-s shot clock (n = 16
observations)-and were compared with regular game-simulation drills (4 vs 4, 40-s
shot clock; n = 16 observations). Measures included mean and peak speed; exercise
intensity ratios, defined as the ratio of time spent performing at high and low
speeds; and the number of high-speed activities performed. RESULTS: Compared with
regular game-simulation drills, 3-versus-3 drills elicited a moderate increase in
mean speed (6.3%; effect size [ES] = 0.7) and the number of high-speed activities
performed (44.1%; ES = 1.1). Minimal changes in speed profiles were observed
during the 30-s shot clock, although moderate to large increases in all measures
were observed during the 15-s shot-clock drills. Classification-specific
differences were further identified, with increased activity observed for high
point players during the 3-versus-3 drill and for low-point players during the 15
s shot clock. CONCLUSION: By reducing the number of players on court and the shot
clock to 15 s, coaches can significantly increase elite WCR players' speed
profiles during game-simulation drills.
PMID- 28422584
TI - Pre- and post-prostatectomy variables associated with pelvic post-operative
radiotherapy in prostate cancer patients: a national registry-based study.
AB - BACKGROUND: In patients with prostate cancer (PCa), the lack of clear guidelines
on the use of radiotherapy after radical prostatectomy (RP) invites unwanted
variation of this treatment. We describe the hazard ratios and probabilities
related to the use of post-RP radiotherapy. MATERIAL AND METHODS: Data were
collected from the Cancer Registry of Norway and nine radiotherapy units. All
patients were diagnosed with a non-metastatic PCa from January 2004 through June
2011. Adjuvant radiotherapy was defined as pelvic radiotherapy initiated <5
months after RP at a PSA <0.2 ng/ml. All other pelvic radiotherapy series were
categorized as salvage radiotherapy, and, combined with adjuvant radiotherapy
they were termed post-RP radiotherapy. RESULTS: Of 6840 prostatectomized
patients, 1170 (17%) had undergone post-RP radiotherapy, mainly as salvage
radiotherapy. The number of adjuvant radiotherapy series almost tripled from
2009. Based on pre-prostatectomy variables (PSA, Gleason score, and clinical risk
group) and findings in the prostatectomy specimens (status of resection margins,
pathological tumor category and Gleason's score), the probability of post-RP
radiotherapy ranged respectively from 14% to 73%, and from 4% to 83%.
CONCLUSIONS: In our study, post-RP radiotherapy was applied in approximately one
in six patients. Based on the combination of PCa-specific variables routinely
available at the time of diagnosis, a patient's probability of post-RP
radiotherapy can be determined before decision of primary treatment strategy,
followed by probability determination based on histopathological variables
emerging from the prostatectomy specimen.
PMID- 28422585
TI - Validation of the IPAQ Against Different Accelerometer Cut-Points in Older Cancer
Survivors and Adults at Risk of Cancer.
AB - The present study investigated the convergent validity of an interview
administered IPAQ long version (IPAQ-L) in an older population by comparison with
objective accelerometry movement data. Data from 52 participants (mean age 67.9
years, 62% male) were included in the analysis. Treadmill derived (TM-ACC: 1,952
5,724 cpm) and free-living physical activity (PA) derived (FL-ACC: 760-5,724 cpm)
accelerometer cut-points were used as criterion. IPAQ-L measures (total PA,
leisure-time, walking-time, sedentary time) were significantly correlated with
accelerometry (P <= .05). Differences in sex were observed. Bland-Altman Limits
of Agreement analysis showed that the IPAQ-L overestimated PA in relation to
accelerometry. Our results show that an interview-administered IPAQ-L shows low
to moderate convergent validity with objective PA measures in this population but
there may be differences between males and females which should be further
investigated.
PMID- 28422586
TI - Biomechanical Determinants of the Reactive Strength Index During Drop Jumps.
AB - The Reactive Strength Index (RSI) is often used to quantify drop-jump (DJ)
performance; however, not much is known about its biomechanical determinants. The
purpose of this study was to investigate the correlations between the RSI and
several biomechanical variables calculated from DJ performed with different
initial drop heights. Twelve male NCAA Division I basketball players performed
DJs from drop heights of 30, 45, and 60 cm. Force plates were used to calculate
DJ performance parameters (ie, DJ height, contact time, and RSI) and DJ
biomechanical variables (ie, vertical stiffness and eccentric/concentric
energetics). Regression analyses were used to assess the correlations between
variables at each drop height, and ANOVAs were used to assess the differences of
all variables across drop heights. Follow-up analyses used 2 neural networks to
determine if DJ performance and biomechanical data could accurately classify DJ
trials by drop-height condition. Vertical-stiffness values were significantly
correlated with RSI at each height but did not change across drop heights.
Surprisingly, the RSI and other DJ parameters also did not vary across drop
height, which resulted in the inability of these variables to accurately classify
DJ trials. Given that vertical stiffness did not change across drop height and
was highly correlated with RSI at each height, the RSI appears to reflect
biomechanical behavior related to vertical stiffness during DJ. However, the
inability of the RSI to accurately classify drop-height condition questions the
use of RSI profiles established from DJs from different heights.
PMID- 28422587
TI - Comparing Campers' Physical Activity Levels Between Sport Education And
Traditional Instruction in a Residential Summer Camp.
AB - BACKGROUND: To date, studies examining physical activity (PA) levels have largely
been dedicated to the school setting, while there is little known about the
activity levels of children who participate in traditional or summer day camps.
METHODS: Participants were 83 11- to 12-year-old campers who partook in either
Sport Education or traditional instruction at a large residential summer camp.
All lessons were video recorded and coded using the System for Observing Fitness
Instruction Time (SOFIT), which categorizes PA levels as well as contextual
characteristics. RESULTS: Results indicated that campers who participated in
Sport Education spent a higher percentage of time (61.6%) engaged in moderate to
vigorous activity than campers in the traditional activity unit (42.2%). In
addition, campers spent less time idly within Sport Education (27.9%), than its
counterpart (39.5%). CONCLUSIONS: These findings indicate that utilizing the
Sport Education model may provide campers with higher levels of PA within this
context.
PMID- 28422588
TI - Alterations in Redox Homeostasis During Recovery From Unexplained
Underperformance Syndrome in an Elite International Rower.
AB - PURPOSE: To examine a diagnosis of unexplained underperformance syndrome (UUPS,
or overtraining syndrome) in an international rower describing a full recovery
and return to elite competition the same year. METHODS: On diagnosis and 4 and 14
mo postdiagnosis, detailed assessments including physiological, nutritional, and
biomarkers were made. RESULTS: Clinical examination and laboratory results for
hematology, biochemistry, thyroid function, immunology, vitamins, and minerals
were unremarkable and did not explain the presentation and diagnosis. Redox
biomarkers including hydroperoxides, plasma antioxidant capacity, red blood cell
glutathione, superoxide dismutase, coenzyme Q10, vitamin E (alpha- and gamma
tocopherol), and carotenoids (lutein, alpha-carotene, beta-carotene) provided
evidence of altered redox homeostasis. The recovery strategy began with 12 d of
training abstinence and nutritional interventions, followed by 6 wk of modified
training. At 4 mo postintervention, performance had recovered strongly, resulting
in the athlete's becoming European champion that same year. Further improvements
in physiological and performance indices were observed at 14 mo postintervention.
Physiologically relevant increases in concentrations of carotenoids were achieved
at each postintervention time point, exceeding the reported critical-difference
values. CONCLUSIONS: Increasing athlete phytonutrient intake may enhance recovery
and tolerance of training and environmental stressors, reducing the risk of
unexplained UUPS. Alterations in redox homeostasis should be considered as part
of the medical management in UUPS. This is the first reported case study of an
elite athlete with alterations in redox homeostasis in conjunction with a
diagnosis of UUPS.
PMID- 28422589
TI - Energy Expenditure in Vinyasa Yoga Versus Walking.
AB - BACKGROUND: Whether the energy cost of vinyasa yoga meets the criteria for
moderate-to-vigorous physical activity has not been established. PURPOSE: To
compare energy expenditure during acute bouts of vinyasa yoga and 2 walking
protocols. METHODS: Participants (20 males, 18 females) performed 60-minute
sessions of vinyasa yoga (YOGA), treadmill walking at a self-selected brisk pace
(SELF), and treadmill walking at a pace that matched the heart rate of the YOGA
session (HR-Match). Energy expenditure was assessed via indirect calorimetry.
RESULTS: Energy expenditure was significantly lower in YOGA compared with HR
Match (difference = 79.5 +/- 44.3 kcal; P < .001) and SELF (difference = 51.7 +/-
62.6 kcal; P < .001), but not in SELF compared with HR-Match (difference = 27.8
+/- 72.6 kcal; P = .054). A similar pattern was observed for metabolic
equivalents (HR-Match = 4.7 +/- 0.8, SELF = 4.4 +/- 0.7, YOGA = 3.6 +/- 0.6; P <
.001). Analyses using only the initial 45 minutes from each of the sessions,
which excluded the restorative component of YOGA, showed energy expenditure was
significantly lower in YOGA compared with HR-Match (difference = 68.0 +/- 40.1
kcal; P < .001) but not compared with SELF (difference = 15.1 +/- 48.7 kcal; P =
.189). CONCLUSIONS: YOGA meets the criteria for moderate-intensity physical
activity. Thus, YOGA may be a viable form of physical activity to achieve public
health guidelines and to elicit health benefits.
PMID- 28422590
TI - Localized Juvenile Spongiotic Gingival Hyperplasia: Report of Two Cases.
AB - OBJECTIVE: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a
painless gingival swelling that histologically exhibits hyperplasia of the non
keratinized stratified squamous epithelium, intercellular edema and spongiosis of
the spinus layer, and exocytosis of inflammatory cells. LJSGH pathogenesis
remains to be elucidated, while a possible origin from the gingival sulcus
epithelium is nowadays proposed. STUDY DESIGN: We report two cases of LJSGH with
immunohistochemical evaluation of cytokeratins (CKs) 18 and 19. RESULTS: Both
cases concerned 12-year-old boys, who presented with a well-circumscribed bright
red pedunculated papillary swelling on the marginal gingiva of the left maxillary
lateral incisor. With the provisional diagnosis of LJSGH, the lesions were
excised under local anesthesia and histological examination supported the final
diagnosis of LJSGH. In both cases, the lesional epithelium showed intense and
mild positivity for CK19 and CK18, respectively, while the adjacent normal
gingival epithelium expressed CK19, but not CK18, only in the basal cell layer.
The postoperative course was uneventful in both patients and no recurrence has
been reported. CONCLUSION: LJSGH is a recently introduced entity that is worth
attention in the clinical pediatric dentistry. Clinical and histological
examination is required for the final diagnosis, while immunohistochemistry has
shed light to LJSGH pathogenesis.
PMID- 28422591
TI - Effect of Papacarie and Alternative Restorative Treatment on Pain Reaction during
Caries Removal among Children: A Randomized Controlled Clinical Trial.
AB - OBJECTIVE: To compare the effect of Papacarie and Atraumatic Restorative
Treatment (ART) on pain and discomfort during caries removal among children.
STUDY DESIGN: Fifty healthy, 4-8 year-old children were equally and randomly
allocated to Papacarie and ART to remove caries from decayed primary teeth. A
randomized, controlled, blinded, two parallel-arms clinical trial was conducted
in the clinic of the Pediatric Dentistry and Dental Public Health Department,
Alexandria University, Egypt in March 2014. Pain and discomfort were assessed
blindly by two independent investigators watching videotaped treatment sessions
using the Sound, Eye and Motor scale (SEM). Their reliability was assessed using
Kappa statistics. The effect of caries removal methods, time spent to remove
caries and other confounders on SEM score was assessed using regression analysis.
RESULTS: Mean time to remove caries using Papacarie and ART was 5.8 and 4.8
minutes, P= 0.005. Median Paparie and ART scores for the S, E and M components
were 1, 1, 1 and 3, 2, 3. Adjusted mean SEM score= 3.6 and 7.8, P <0.0001. Method
of caries removal was the only factor significantly affecting pain and
discomfort. CONCLUSION: Papacarie is associated with minimal pain during caries
removal from primary teeth compared to ART, although it has longer working time.
PMID- 28422592
TI - Role of Colors in Pediatric Dental Practices.
AB - OBJECTIVE: This study evaluated the association between colors and emotions in a
pediatric dental population. STUDY DESIGN: In this randomized cross-sectional
study, 100 children aged 6-12 years were categorized as non-anxious and anxious
using Corah's Dental Anxiety Scale-Revised. They were then instructed to color
two cartoon faces, one depicting happiness emotion and the other, sadness, with
any of six colors provided. Data obtained were statistically analyzed. RESULTS:
The mean Corah's Dental Anxiety scores were 11.7 and 4.97 for the anxious and non
anxious children, respectively. Both groups expressed the highest preference for
the color yellow for happiness emotion. No significant differences were observed
between color choices in either group (p>0.05), except for black which was not
chosen by any child for happiness (p<0.005). Children in both groups
significantly preferred red for sadness emotion. No significant differences were
observed between color choices in the anxious group (p>0.05). In the non-anxious
group, yellow assumed significant preference over green (p<0.05). CONCLUSIONS:
Yellow was the most-preferred color and black, the least-preferred, for happiness
emotion, whereas, for sadness emotion, red and green were the most- and least
preferred colors, respectively. Color preference was not affected by the presence
of dental anxiety.
PMID- 28422593
TI - Fundamentals in Biostatistics for Investigation in Pediatric Dentistry: Part II
Biostatistical Methods.
AB - The main purpose of the second part of this series was to provide the reader with
some basic aspects of the most common biostatistical methods employed in health
sciences, in order to better understand the validity, significance and
reliability of the results from any article on Pediatric Dentistry. Currently, as
mentioned in the first paper, Pediatric Dentists need basic biostatistical
knowledge to be able to apply it when critically appraise a dental article during
the Evidence-based Dentistry (EBD) process, or when participating in the
development of a clinical study with dental pediatric patients. The EBD process
provides a systematic approach of collecting, review and analyze current and
relevant published evidence about oral health care in order to answer a
particular clinical question; then this evidence should be applied in everyday
practice. This second report describes the most commonly used statistical methods
for analyzing and interpret collected data, and the methodological criteria to be
considered when choosing the most appropriate tests for a specific study. These
are available to Pediatric Dentistry practicants interested in reading or
designing original clinical or epidemiological studies.
PMID- 28422594
TI - Intentional Replantation of an Immature Incisor with a Transverse Root Fracture
and Endo-Perio Condition: 4 Year Follow-Up.
AB - This case report describes the importance of continual examination for dental
trauma and the efficacy of intentional replantation with retrograde root canal
filling for a transverse root fracture in an immature incisor accompanied by
subsequent periodontal-endodontic disease. In the treatment of traumatically
fractured roots in immature incisors, continual examination is indispensable for
the final diagnosis because roots in immature teeth are less calcified, resulting
in less detailed radiological examinations. Thus, common dental trauma
complications such as pulp necrosis may appear months after the initial
examination. Endodontic treatment for transverse root fracture is mainly
determined according to radiographic examination findings; for fractured immature
roots, apexification with calcium hydroxide of the coronal fragment is generally
applied. However, this method requires removal of considerable amounts of enamel
and dentin to allow access to the cavity for preparation, which may increase the
risk of future fractures. In contrast, intentional replantation with retrograde
root canal filling does not require the removal or long-term application of
calcium hydroxide. However, it requires careful extraction of the tooth,
maintenance of root wetness during the extraoral procedure, rigid splinting, and
oral hygiene control. Management of tooth mobility is also important in the post
replantation course.
PMID- 28422595
TI - Microleakage of Sealants after Phosphoric Acid, Er: YAG Laser and Air Abrasion
Enamel Conditioning: Systematic Review and Meta-Analysis.
AB - PURPOSE: The aim of this systematic review and meta-analysis is to answer the
focused question: Does the application of phosphoric acid, Er:YAG laser and air
abrasion enamel conditioning methods previous to the oclusal sealant application
in human permanent molars influence the microleakage? STUDY DESIGN: A literature
research was carried out in the Pubmed Medline, Web of Science, Scopus and
Cochrane databases using with the MeSH terms and keyword search strategy. A
supplemental hand search of the references of retrieved articles was also
performed. Inclusion criteria comprised ex vivo studies (extracted teeth) with
permanent human teeth that used chemical (phosphoric acid) or mechanical (Er:YAG
laser and air abrasion) conditioning methods previous the sealant application.
The studies should evaluate microleakage as an outcome. Meta-analysis pooled plot
were obtained comparing the microleakage after pre-treatment with phosphoric
acid, Er:YAG and air abrasion enamel conditioning for sealant application using
RevMan software. RESULTS: The search resulted in 164 articles, 55 records were
excluded because they were duplicated. The analysis of titles and abstracts
resulted in the exclusion of 105 studies. Four studies were included in the
systematic review and the meta-analysis. According to the risk of bias
evaluation, the four studies were considered low risk of bias. The meta-analysis
showed that phosphoric acid had lower microleakage than Er:YAG laser (p < 0.001)
and air abrasion (p < 0.001), with heterogeinity of I2 = 0% and I2 = 71%,
respectively. It was not found statistical difference when compared phosphoric
acid and phosphoric acid combined with Er:YAG laser and air abrasion (p > 0.05).
CONCLUSION: The evidence supports that the pretreatment with phosphoric acid
leads lower microleakage in oclusal sealants than Er:YAG laser and air abrasion.
PMID- 28422596
TI - Agenesis of Third Molars among Turkish Children between the Ages of 12 and 18
Years: A Retrospective Radiographic Study.
AB - PURPOSE: The aim of this study was to investigate the agenesis of third molars
(M3) in children with permanent dentition in a limited population in the province
of Izmir, Turkey. STUDY DESIGN: The panoramic radiographs of 773 patients (457
females, 316 males) were evaluated retrospectively at the Dental Hospital of
Ministry of Health in Izmir, Turkey. The patients' ages ranged from 12-18 years.
The agenesis of M3 teeth was investigated according to maxilla and mandible and
right and left distribution. RESULTS: In 593 of the patients (76.7%), all of the
M3 teeth were present in the mouth; while in the other 180 (23.3%) patients,
agenesis of a varying number of M3 teeth was identified. In 31 patients (4.0%),
total M3 tooth agenesis was observed. A statistically significant relationship
was not found between gender and M3 teeth (p=0.091). A statistically significant
relationship was found between congenital M3 tooth agenesis and the maxilla
(14.3%) and mandible (9.6%) (p<0.001). However, a statistically significant
difference was not found between the right-left area of the jaw (p=0.100).
CONCLUSION: As a result, while all M3 teeth were present in 76.71% of the
population studied in the province of Izmir, agenesis of one or more than one M3
tooth was found in the other 23.29% of the patients studied.
PMID- 28422597
TI - Post-Discharge Events Occurring after Dental Treatment under Deep Sedation in
Pediatric Patients.
AB - PURPOSE: Deep sedation is often required in dentistry for treating children with
uncooperative behavior. We assessed immediate post-sedation events during the
first 24 hours after dental treatment under deep sedation in children, and
examined correlations to a number of variables. STUDY DESIGN: Information was
collected from medical files for a convenience sample of children between the
ages of 1 and 16, who were treated under deep sedation at one clinic (propofol
alone or combined with a sedative agent). Parents were interviewed by telephone
regarding the first 24 hours following treatment. RESULTS: Among 32 children
under age 6 years, 26 (81.3%) had at least one post sedation complication,
compared to 19/22 (86.4%) aged 6 and older, p>0.05. According to parent report,
13 (59.1%) of the older children had pain, compared to 6 (18.8%) of the younger
ones, p=0.002. For no patient in the younger group compared to 18.2% in the older
group was dizziness reported as a complication, p=0.023. Among those who received
a sedative agent, 93.3% had one or more complications; 26.7% had nausea or
vomiting. The respective rates were 79.5% and 5.1% among those treated only with
propofol. CONCLUSIONS: Though safe, deep sedation poses complications and adverse
events.
PMID- 28422598
TI - The Use of Restorative Materials in Primary Molars among Pediatric Dentists in
Israel.
AB - OBJECTIVES: To assess the current choice of various restoration materials among
Israeli pediatric dentists according to seniority and specialty. STUDY DESIGN:
Participating dentists completed a 23-item questionnaire on their qualifications,
type of practice and preference of restorative material. RESULTS: Seventy-five
dentists (average age 46.27+/-12.6 years, 58 females) participated. Forty-one
were specialist pediatric dentists and 34 were general practitioners. Amalgam was
preferred by 49.3%, followed by composite (41.3%), glass ionomer cement (5.3%)
and compomer (4%). Only 13.3% of the dentists thought amalgam bears environmental
and health hazards, compared to 49.3% for composite. Satisfaction was high for
amalgam and composite, less for glass ionomer cements and least for compomer.
General practitioners preferred amalgam (70.6%) while pediatric dentists
preferred composite (51.2%), P < 0.003. CONCLUSIONS: Amalgam and composite were
the materials of choice among the participating Israeli dentists. Most of them
(86.7%) responded that amalgam does not possess any health issues. Their
satisfaction with the restoration materials was highest for amalgam and
composite, a choice significantly affected by whether they were in general
practice (amalgam) or specialized in pediatric dentistry (composite).
PMID- 28422599
TI - Sleep Bruxism and Anxiety Impacts in Quality of Life Related to Oral Health of
Brazilian Children and their Families.
AB - OBJECTIVE: This study aimed to assess the impact of parent reported sleep
bruxism, trait anxiety and sociodemographic/socioeconomic features on quality of
life related to oral health (OHRQoL) of children and their families. STUDY
DESIGN: Healthy children aged 3-7 years, with (n=34) and without (n=32) bruxism
were select for this study. Data was collected by applying the following
instruments: The Early Childhood Oral Health Scale (B-ECOHIS) and Trait-anxiety
Scale (TAS). The sociodemographic/socioeconomic characteristics were obtained by
interviews with parents. Multiple logistic regression tests were performed to
observe the influence of sociodemographic/socioeconomic characteristics, bruxism
and trait-anxiety on the children's OHRQoL. RESULTS: No association between sleep
bruxism and all evaluated sociodemographic/socioeconomic conditions, with
exception of being the only child (p=0.029), were observed. Mean B-ECOHIS and TAS
scores were different (p<0.05) between children with (3.41 +/- 4.87; 45.09 +/-
15.46, respectively) and without (0.63 +/- 1.28; 29.53 +/- 11.82, respectively)
bruxism. Although an association between bruxism and OHRQoL (p=0.015) was
observed, it was dropped (p=0.336; OR=1.77) in the logistic regression model.
Trait anxiety was the variable responsible for the impact on the OHRQoL of
children (p=0.012; OR=1.05). CONCLUSION: Our results indicated anxiety as the
main factor that interfered in the OHRQoL of children with sleep bruxism.
PMID- 28422600
TI - Effect of a School-Based Supervised Tooth Brushing Program In Mexico City: A
Cluster Randomized Intervention.
AB - : Large-scale school-based programs effectively provide health education and
preventive strategies. SaludARTE is a school-based program, including supervised
tooth brushing, implemented in 51 elementary schools in Mexico City. OBJECTIVES:
To assess the three-month efficacy of supervised tooth brushing in reducing
dental plaque, gingival inflammation, and bleeding on probing in schoolchildren
participating in SaludARTE. STUDY DESIGN: This was a pragmatic cluster randomized
intervention, with two parallel branches. Four randomly selected schools
participating in SaludARTE (n=200) and one control school, which did not
participate in the program (CG) (n=50), were assessed. Clusters were not randomly
allocated to intervention. The main outcomes were as follows: mean percentage
gingival units with no inflammation, dental surfaces with no dental plaque, and
gingival margins with no bleeding. The independent variable was supervised tooth
brushing at school once a day after a meal. Guardians and children responded to a
questionnaire on sociodemographic and oral hygiene practices, and children were
examined dentally. Mean percentage differences were compared (baseline and follow
up). RESULTS: A total of 75% of guardians from the intervention group (IG) and
77% from the CG answered the questionnaire. Of these, 89.3% were women, with a
mean age of 36.9+/-8.5 years. No differences in sociodemographic variables were
observed between groups, and 151 children from the IG and 35 from the CG were
examined at baseline and follow-up. Mean percentage differences for plaque-free
surfaces (8.8+/-28.5%) and healthy gingival units (23.3%+/-23.2%) were
significantly higher in the IG. CONCLUSION: The school-supervised tooth brushing
program is effective in improving oral hygiene and had a greater impact on plaque
and gingivitis than on gingival bleeding. It is necessary to reinforce the oral
health education component of the program.
PMID- 28422601
TI - Degradation of Resin Restorative Materials by Streptococcus Mutans: A Pilot
Study.
AB - OBJECTIVE: To evaluate the degradation of three resin based restorative materials
by S Mutans. STUDY DESIGN: Class I cavity was prepared in extracted premolars and
were randomly divided into 3 groups (Group I - Conventional composite (CC), Group
II - Resin Modified GIC and Group III-Giomer). Teeth were then restored by
respective restorative material and equally divided in two subgroups (Control and
Experimental). Experiment subgroup samples were then incubated in 2 ml of BHI
with 1:10 dilution of SM (MTCC-497) grown overnight in BHI whereas control
subgroup samples were incubated in BHI without SM. The incubation solution was
collected at 2,14 and 30 days interval, and the analysis for identification and
quantification of Bis-HPPP was done by High performance Liquid Chromatography.
RESULTS: Statistical analysis of the collected data revealed a statistically
increased Bis HPPP production in the presence of SM in all the tested materials,
with minimum in Resin Modified GIC and a maximum in Conventional Composite (CC).
CONCLUSION: SM degrades the resin based restorative materials & among the tested
materials Resin Modified GIC appears to be most Biostable.
PMID- 28422602
TI - Does Bonding Approach Influence the Bond Strength of Universal Adhesive to Dentin
of Primary Teeth?
AB - OBJECTIVE: To evaluate the effect of bonding strategy on microtensile bond
strength (MUTBS) of a new universal adhesive system to primary tooth dentin.
STUDY DESIGN: Flat dentin surfaces from 25 primary molars were assigned to 5
groups according to the adhesive and bonding approach: Adper Single Bond 2 (two
step etch-and-rinse adhesive) and Clearfil SE Bond (two-step self-etch system),
as controls; Scotchbond Universal Adhesive-self-etch, dry or wet-bonding etch-and
rinse strategies. Composite buildups were constructed and the teeth were
sectioned to obtain bonded sticks (0.8 mm2) to be tested under tension at
1mm/min. The MUTBS means were analyzed by one-way ANOVA and Tukey's tests (alpha
= 0.05). Failure mode was evaluated using a stereomicroscope (400*). RESULTS:
Universal adhesive applied following both dry and wet-bonding etch-and-rinse
strategies showed similar bond strength compared with control adhesive systems.
Self-etch approach resulted in the lowest MUTBS values. For all groups,
adhesive/mixed failure prevailed. The percentage of premature debonded specimens
was higher when the universal adhesive was used as self-etch mode. CONCLUSION:
The universal adhesive does not share the same versatility of being used in the
etch-and-rinse and self-etch approaches; however, the use of the new adhesive
following either wet or dry-bonding may be a suitable option as alternative to
two-step etch-and-rinse adhesive protocol.
PMID- 28422603
TI - Factors Responsible for Unfavorable Dental Arch Relationship in non Syndromic
Unilateral Cleft Lip and Palate Children.
AB - OBJECTIVES: Multiple factors are whispered to be crucial cause of unfavourable
dental arch relationship in cleft lip and palate (CLP).This study aims to
evaluate the dental arch relationship of Bangladeshi children with non syndromic
unilateral cleft lip and palate (UCLP) following cheiloplasty and palatoplasty.
Also to explore the various congenital (UCLP type, UCLP side, family history of
cleft, family history of class III) and environmental (cheiloplasty,
palatoplasty) factors that affects dental arch relationship of UCLP patients.
STUDY DESIGN: This was a retrospective study where 84 dental models were taken
before orthodontic treatment and alveolar bone grafting. The mean age was 7.69+/-
2.46 (mean+/- SD). The dental arch relationship was assessed by GOSLON (Great
Ormond Street, London and Oslo) Yardstick. According to GOSLON Yardstick, five
categories are rated; named- 1: excellent; 2: good; 3: fair; 4: poor; 5: very
poor. Also the groups have been dichotomized into favorable (category ratings 1
3) and unfavorable (category ratings 4 and 5) groups. Kappa statistics was used
to evaluate the intra- and inter-examiner agreements and logistic regression
analysis was used to explore the responsible factors that affect dental arch
relationship. RESULTS: Total 37 subjects (44% of all subjects) were categorized
into unfavourable group (category rating 4 and 5) using GOSLON yardstick. Intra-
and inter-examiner agreements were very good. The mean GOSLON score was 3.238.
Using crude and stepwise backward regression analysis, significant association
was found between family history of skeletal class III malocclusion (p = 0.015
and p = 0.014 respectively) and unfavourable dental arch relationship. Complete
UCLP (p = 0.054) and left sided UCLP (p = 0.053) also seemed to be correlated but
not significant with unfavourable dental arch relationship using crude and
stepwise backward regression analysis respectively. CONCLUSION: This analysis
suggested that family history of skeletal class III was significantly correlated
with unfavourable dental arch relationship of Bangladeshi UCLP children.
PMID- 28422604
TI - Examination of Intramuscular and Skin Temperature Decreases Produced by the
PowerPlay Intermittent Compression Cryotherapy.
AB - CONTEXT: Previous research has found ice bags are more effective at lowering
intramuscular temperature than gel packs. Recent studies have evaluated
intramuscular temperature cooling decreases with ice bag versus Game Ready and
with the PowerPlay system wetted ice bag inserts; however, intramuscular
temperature decreases elicited by PowerPlay with the standard frozen gel pack
inserts have not been examined. OBJECTIVE: Evaluate the rate and magnitude of
cooling using PowerPlay with frozen gel pack (PP-gel) option, PowerPlay with
wetted ice bag (PP-ice) option, and control (no treatment) on skin and
intramuscular temperature (2 cm subadipose). DESIGN: Repeated-measures
counterbalanced study. SETTING: University research laboratory. PATIENTS OR OTHER
PARTICIPANTS: Twelve healthy college-aged participants (4 men and 8 women; age =
23.08 (1.93) y, height = 171.66 (9.47) cm, mass = 73.67 (13.46) kg, and
subcutaneous thickness = 0.90 (0.35) cm). INTERVENTION(S): PowerPlay (70 mm Hg)
with either wetted ice bag or frozen gel pack was applied to posterior aspect of
nondominant calf for 30 minutes; control lay prone for 30 minutes. Participants
underwent each treatment in counterbalanced order (minimum 4 d, maximum 10 d
between). MAIN OUTCOME MEASURE(S): Muscle temperature was measured via 21-gauge
catheter thermocouple (IT-21; Physitemp Instruments, Inc). Skin temperature was
measured via surface thermocouple (SST-1; Physitemp Instruments, Inc). RESULTS:
Significant treatment-by-time interaction for muscle cooling (F10,80 = 11.262, P
= .01, [Formula: see text], observed beta = 0.905) was observed. PP-ice cooled
faster than both PP-gel and control from minutes 12 to 30 (all Ps < .05); PP-gel
cooled faster than control from minutes 18 to 30 (all Ps < .05). Mean decreases
from baseline: PP-ice = 4.8 degrees C (2.8 degrees C), PP-gel = 2.3 degrees C
(0.8 degrees C), and control = 1.1 degrees C (0.4 degrees C). Significant
treatment-by-time interaction for skin cooling (F10,80 = 23.920, P = .001,
[Formula: see text], observed beta = 0.998) was observed. PP-ice cooled faster
than both PP-gel and control from minutes 6 to 30 (all Ps < .05); PP-gel cooled
faster than control from minutes 12 to 30 (all Ps < .05). Mean decreases from
baseline: PP-ice = 14.6 degrees C (4.8 degrees C), PP-gel = 4.0 degrees C (0.9
degrees C), and control = 1.0 degrees C (1.0 degrees C). CONCLUSIONS: PP-ice
produces clinically and statistically greater muscle and skin cooling compared
with PP-gel and control.
PMID- 28422605
TI - Time to First Cigarette, Physical Activity, and Pulmonary Function in Middle-aged
to Older Adult Smokers.
AB - BACKGROUND: How addiction severity relates to physical activity (PA), and if PA
moderates the relation between PA and lung function among smokers, is unknown.
This study explored the independent and interactive associations of nicotine
addiction severity and PA with lung function. METHODS: The study used cross
sectional data from 343 adult smokers aged 40 to 79 participating in the 2009-10
and 2011-12 National Health and Nutrition Examination Survey. Assessed were the
independent relations of nicotine addiction severity, as measured by the time to
first cigarette (TTFC), and average daily minutes of moderate and vigorous PA
with lung function ratio (FEV1/FVC). Additional analysis examined whether PA
moderated the relationship between addiction severity and lung function. RESULTS:
Greater lung function was independently associated with moderate PA and later
TTFC, but not vigorous PA, when controlling for cigarettes per day (CPD), past
month smoking, ethnicity, years smoked, and gender (P-values < .05). PA did not
moderate the association between addiction severity (TTFC) and lung function (P =
.441). CONCLUSION: Among middle-aged to older smokers, increased PA and lower
addiction severity were associated with greater lung function, independent of
CPD. This may inform research into the protective role of PA and identification
of risk factors for interventions.
PMID- 28422606
TI - Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.
PMID- 28422607
TI - Delusional Disorder Arising From a CNS Neoplasm.
AB - Erotomania arising from a central nervous system (CNS) neoplasm has not been
previously described. Here, we present the first known case, to our knowledge, of
erotomania with associated persecutory delusions arising following diagnosis and
treatment of a left frontal lobe brain tumor.
PMID- 28422608
TI - Six new soil-inhabiting Cladosporium species from plateaus in China.
AB - Cladosporium species are ubiquitous in various environments but are hitherto
rarely isolated from soil. In the present study, six new Cladosporium species
inhabiting the plateau soils of China are described as C. neopsychrotolerans, C.
paralimoniforme, C. prolongatum, C. sinuatum, C. tianshanense, and C.
verruculosum. These species are phylogenetically distinct and morphologically
different from known species. This study increased the number of species
classified in the C. cladosporioides and C. herbarum complexes and revealed
Chinese plateau soil as a rich niche of Cladosporium species diversity.
PMID- 28422610
TI - Joint bent-cable Tobit models for longitudinal and time-to-event data.
AB - In this article, we show how to estimate a transition period for the evolvement
of drug resistance to antiretroviral (ARV) drug or other related treatments in
the framework of developing a Bayesian method for jointly analyzing time-to-event
and longitudinal data. For HIV/AIDS longitudinal data, developmental trajectories
of viral loads tend to show a gradual change from a declining trend after
initiation of treatment to an increasing trend without an abrupt change. Such
characteristics of trajectories are also associated with a time-to-event process.
To assess these clinically important features, we develop a joint bent-cable
Tobit model for the time-to-event and left-censored response variable with
skewness and phasic developments. Random effects are used to determine the
stochastic dependence between the time-to-event process and response process. The
proposed method is illustrated using real data from an AIDS clinical study.
PMID- 28422609
TI - Isotemporal Analysis of the Association of Objectively Measured Physical Activity
With Depressive Symptoms: Results From Hispanic Community Health Study/Study of
Latinos (HCHS/SOL).
AB - BACKGROUND: The burden of depression among Hispanics/Latinos indicates the need
to identify factors related to depressive symptoms. This paper examines the
relationship of physical activity (PA) and sedentary behavior (SB) with
depressive symptoms in Hispanic/Latinos. METHODS: The Hispanic Community Health
Study / Study of Latinos (HCHS/SOL) is a population-based, cohort study of
Hispanic/Latinos in 4 United States metropolitan areas. Objectively measured PA
was coded into: sedentary behavior (SB), light-intensity (LPA), moderate
intensity (MPA), and vigorous-intensity (VPA); and the Center for Epidemiological
Studies Depression Scale-10 assessed depressive symptoms. Multiple regression
analysis utilizing isotemporal substitution, adjusted for relevant covariates,
examined PA as predictors of depressive symptoms. RESULTS: Substitution of 1 hour
of SB with VPA resulted in a significant decrease in depressive symptoms (beta =
1.215, P = .021). Similar decreases were observed when VPA replaced LPA (beta =
1.212, P = .021) and MPA (beta = -1.50 P = .034). MPA and LPA were not associated
with lower depressive symptoms. CONCLUSIONS: Previous research has focused on the
relationship of MVPA on depressive symptoms. Our results suggest these constructs
should be examined separately as they may have unique relationships with
depressive symptoms. The association of SB with greater depressive symptoms
confirms previous reports.
PMID- 28422611
TI - Predictors of Hearing Protection Use Among Industrial Workers.
AB - Promoting the use of hearing protection devices (HPDs) can prevent noise-induced
hearing loss (NIHL) among workers who are exposed to excessive noise. In the
present study, the authors examine factors that may explain HPD use among
industrial workers from 15 manufacturing plants in Thailand. Participants
consisted of 268 randomly selected workers exposed to harmful noise levels for
which routine HPD use was required. Logistic regression analysis of study
variables revealed the most powerful predictors of HPD use were perceived hearing
status ( b = 0.66, p < .001) and interpersonal factors (i.e., role modeling and
interpersonal support; b = 0.20, p < .001). Together, these variables correctly
classified 63.4% of the cases. These findings have implications for interventions
aimed at motivating workers to use HPDs regularly.
PMID- 28422612
TI - Assessing Non-Suicidal Self-Injury in the Laboratory.
AB - The majority of non-suicidal self-injury (NSSI) research has used self- or
clinician-rated measures of behavior which (a) are subject to reporting biases,
or (b) have limited use in experimental designs that could illuminate causal
relationships. Laboratory-based behavioral tasks have therefore been developed to
assess NSSI-related behaviors more directly. We reviewed the behavioral methods
that have been developed to assess NSSI tendencies or behaviors over the past 30
years. Several categories of laboratory analogues were identified: NSSI-related
stimuli (e.g., NSSI pictures, implicit association tasks, guided imagery),
experimenter administered pain stimuli (e.g., cold, heat, pressure, shock, and
blade), and self-selected pain stimuli (e.g., cold and shock). These behavioral
methods assess various aspects of NSSI and all have distinct advantages and
shortcomings. Overall, these approaches have made significant contributions to
the field complementing self- and clinician-ratings.
PMID- 28422613
TI - The Impact of Prospective Telemedicine Implementation in the Management of
Childhood Acute Lymphoblastic Leukemia in Recife, Brazil.
AB - BACKGROUND: A gap in childhood cancer outcomes remains between developed and
developing countries. Persistence of this gap may be caused by financial, social,
or educational disparities. Twinning and distance learning initiatives may
improve such disparities. Integrating telemedicine into pediatric oncology
twinning programs enhances education and facilitates patient-centered capacity
building. MATERIALS AND METHODS: We performed an analysis of Web-based meetings
held from August 2005 through July 2009 between the International Outreach
Program at St. Jude Children's Research Hospital and the Instituto Materno
Infantil de Pernambuco (IMIP) in Recife, Brazil. We determined the effect of
these online conferences on the development and implementation of an innovative
protocol for children with acute lymphoblastic leukemia (ALL) at IMIP. RESULTS:
Meetings occurred in 45 months of the 48-month study period with an average of
two meetings per month. A total of 163 new patients were discussed during the
study period; we retrieved documentation of patient-related discussions for 147
of them, constituting 286 discussions. On average, each patient was discussed 1.9
times (range, 1-15 discussions/patient). Compared with that of the era predating
the online meetings (1993-2005), overall mortality, early death, and relapse of
patients with ALL decreased after the telemedicine program was instituted at
IMIP. DISCUSSION: Personal dedication and institutional support are essential for
successful telemedicine initiatives. Documentation and archival of meetings are
important for accurately measuring outcomes and developing methods for improved
care. CONCLUSIONS: Integration of telemedicine into twinning programs facilitates
communication about interventions, leading to improved outcomes of pediatric
patients with cancer.
PMID- 28422614
TI - Electronic Follow-Up of Developing World Cleft Patients: A Digital Dream?
AB - OBJECTIVE: To identify potential access to telemedicine follow-up of children
with clefts operated on a humanitarian mission. METHODS: A cross-sectional study
of parents of children presenting to a humanitarian cleft lip and palate mission
in a Provincial Hospital in the Philippines. A purpose designed questionnaire was
used to assess access to electronic and digital resources that could be used to
aid follow-up. Forty-five (N = 45) parents of children having primary cleft lip
and or palate surgery participated. There were no interventions. Access to the
Internet was through Parent Perceived Affordability of Internet Access and Parent
Owned Devices. RESULTS: Thirty-one (N = 31) respondents were female. There was
93% mobile phone ownership. The mean distance traveled to the clinic was 187 km.
Majority (56%) were fluent in English. Thirty-one percent accessed the Internet
daily. Sixteen percent reported use of e-mail. Fifty-one percent accessed the
Internet on a mobile device, and short message service use was the most
affordable means of communication. CONCLUSIONS: Due to perceived unaffordability
and low levels of access to devices with cameras and the Internet, as well as
issues with privacy, we cannot recommend relying on electronic follow-up of
patients in the developing world.
PMID- 28422615
TI - Understanding How Sexual and Gender Minority Stigmas Influence Depression Among
Trans Women and Men Who Have Sex with Men in India.
AB - PURPOSE: Few studies have assessed how sexual and gender minority stigmas affect
the mental health of trans women and self-identified men who have sex with men
(MSM) in India, populations with a high HIV burden. We tested whether social
support and resilient coping act as mediators of the effect of sexual and gender
minority stigmas on depression as proposed by Hatzenbuehler's psychological
mediation framework, or as moderators based on Meyer's minority stress theory.
METHODS: We conducted a cross-sectional survey among trans women (n = 300) and
MSM (n = 300) recruited from urban and rural sites in India. Standardized scales
were used to measure depression (outcome variable), transgender identity
stigma/MSM stigma (predictor variables), and social support and resilient coping
(tested as moderators and parallel mediators). The mediation and moderation
models were tested separately for trans women and MSM, using Hayes' PROCESS macro
in SPSS. RESULTS: Participants' mean age was 29.7 years (standard deviation 8.1).
Transgender identity stigma and MSM stigma were significant predictors
(significant total and direct effects) of depression, as were social support and
resilient coping. Among trans women and MSM, social support and resilient coping
mediated (i.e., significant specific indirect effects), but did not moderate, the
effect of stigma on depression, supporting the psychological mediation framework.
CONCLUSION: Sexual and gender minority stigmas are associated with depression,
with social support and resilient coping as mediators. In addition to stigma
reduction interventions at the societal level, future interventions should focus
on improving social support and promoting resilience among trans women and MSM in
India.
PMID- 28422616
TI - To Give Epinephrine or Not to Give Epinephrine-That Is (No Longer) The Question!
AB - It is vital that school nurses be able to assess students who are at risk for
anaphylaxis and that nurses train school staff to identify the symptoms of a life
threatening allergic reaction. When a reaction occurs, school nurses and staff
must be prepared to administer epinephrine immediately.
PMID- 28422617
TI - Hidden Devices in the School Setting: What the Nurse Needs to Know About Shunts.
AB - The role of school nurse today not only includes making a thorough assessment of
the child but also the knowledge and skill to understand hidden medical devices.
As of 2011, there were approximately 14.6 million children in the United States
living with special health care needs. Many of these children could have hidden
medical devices. The Specialized Health Needs Interagency Collaboration (SHNIC)
program at the Kennedy Krieger Institute received requests for in-person training
regarding ventriculoperitoneal (VP) shunts.
PMID- 28422618
TI - School Nurses on the Front Lines of Medicine: Connecting the Dots: SCRIPTS for
Success in the Evaluation of Pediatric Rashes.
AB - Although skin rashes may not necessarily prompt a visit to the school nurse's
office, a rash associated with other systemic symptoms, such as fever, headache,
difficulty swallowing or breathing, weakness, or abdominal pain, may cause a
child to visit your office. This article describes the initial assessment and
management of skin rashes in children and adolescents and delineates reasons that
may prompt the school nurse to transfer a student with a rash to a local
emergency department.
PMID- 28422619
TI - The Role of the School Nurse in the Special Education Process: Part I: Student
Identification and Evaluation.
AB - Every U.S. student is entitled to a free and appropriate education. School
districts must identify and evaluate any child who they find is unable to engage
fully in learning as a participant in the general education curriculum. The
Individuals with Disabilities Education Act of 2004 requires that these students
be assessed by qualified individuals in any areas that may be impacting learning,
including health, vision, hearing, social and emotional status, communicative
status, and motor abilities. The school nurse, as the health expert, has an
important role to play as a member of the special education team in evaluating
whether a student has health concerns that are impacting learning and how health
barriers to learning might be reduced. As part of the full and individual
evaluation, the school nurse composes a written report and makes recommendations
to the team regarding necessary health services and other modifications the
student may need. This article (Part 1 of 2) will outline the school nurse's role
in identification and evaluation of students who may benefit from special
education services.
PMID- 28422620
TI - The Time Has Come for School Nurses and Social Media.
PMID- 28422621
TI - Historic Leadership: One Courageous School Nurse's Heroic Journey-Part 3.
AB - School nursing practice establishes itself in the midst of both education and
nursing philosophies, ethics, standards, laws, and regulations. Treading these
two worlds is difficult at times and requires that a school nurse possess a
strong foundational knowledge base, seek professional collaboration, and navigate
conflicting professional demands in order to promote student and public safety.
This article is Part 3 of a four-part series that recounts the inspiring story of
a school nurse, Ellen Johnsen, who did just that back in the 1980s in Broken
Arrow, Oklahoma. Part 3 describes the publication of the Attorney General's
opinion validating the illegality of the school district's medication
administration policy, the lawsuit Ellen brought against the Broken Arrow Public
Schools, and the appeal of the final decision in that lawsuit. The purpose of
this series is to enhance understanding of the legal parameters governing school
nurse practice, provide examples of ethical decision making, and review the
challenges associated with serving as a leader.
PMID- 28422622
TI - Framework for 21st Century School Nursing Practice: Framing Professional
Development.
AB - The NASN Code of Ethics upholds that it is the responsibility of the school nurse
to maintain competency and pursue personal and professional growth. Designing
professional development activities that are relevant and support the needs of
the school nurse can be a challenge. The Framework for 21st Century School
Nursing Practice provides a model rooted in evidence-based standards of practice
that can be utilized to assess an existing professional development program and
identify gaps in learning opportunities. Nurse leaders can use the Framework for
21st Century Nursing Practice to provide a roadmap toward a professional
development program that will be meaningful to school nurse staff, help restore
or maintain joy in their practice, and allow them to achieve the goal of
advancing the well-being, academic success, and lifelong achievement and health
of students.
PMID- 28422623
TI - Knee stiffness and viscosity: New implementation and perspectives in prosthesis
development.
AB - The pendulum test is a method applied to measure passive resistance of the knee.
A new and simple pendulum test with instrumentation based on infrared camera was
used to evaluate knee stiffness and viscosity on a female human cadaver. The
stiffness and viscosity were calculated based on the kinetic data. During the
measurements, the periarticular and intraarticular soft tissue of the knee was
gradually removed to determine the stiffness and viscosity as a function of the
tissue removal rate. The measurements showed that the removal of tissue around
the joint reduces the damping of leg oscillation, and therefore decreases the
stiffness and viscosity. The contribution to knee joint damping was 10% for the
skin, 20% for ligaments, and 40% for muscles and tendons. Tissue removal has a
very large impact on the knee stiffness and viscosity.
PMID- 28422624
TI - Occupational Therapy's Role in Cancer Survivorship as a Chronic Condition.
AB - Improved medical care has resulted in a documented increase in cancer survivors
in the United States. Cancer survivors face challenges in participation across
all facets of life as a result of the cancer and subsequent cancer treatments.
Long-term and late-term sequelae can result in impairments in neurological
systems, decreased stamina, loss of range of motion, and changes in sensation and
cognition. These impairments are often long lasting, which categorizes cancer
survivorship as a chronic condition. This categorization presents treatment
challenges, especially in creating rehabilitation and habilitation service
options that support cancer survivors. Occupational therapy provides a unique
focus that can benefit cancer survivors as they face limitations in participation
in all aspects of daily living. Research, advocacy, and education efforts are
needed to focus on the specific rehabilitation and habilitation needs of cancer
survivors to increase access to occupational therapy's distinct value.
PMID- 28422625
TI - Characteristics of Students Receiving Occupational Therapy Services in Transition
and Factors Related to Postsecondary Success.
AB - OBJECTIVE: This study had a twofold purpose: (1) identify the characteristics of
people with disabilities who received occupational therapy services during their
transition to adulthood and (2) determine factors associated with their
successful postsecondary transition. METHOD: This study was a secondary analysis
of National Longitudinal Transition Study-2 data. Data analyses include
descriptive statistics, binary logistic regression, and simple linear regression.
RESULTS: Autism, cerebral palsy, and intellectual disability were the most
commonly reported disability classifications. Participation in postsecondary
education was significantly associated with functional use of arms and hands.
Postsecondary employment was significantly associated with verbal comprehension.
Participation in community activities was significantly related to students'
health status, and participation in community service was significantly related
to students' functional use of arms and hands. CONCLUSION: Providing transition
services to students with disabilities remains an emerging area of practice.
Occupational therapy practitioners may contribute to transition teams by
intervening to improve functional abilities and health status.
PMID- 28422626
TI - Navigating the Hidden Curriculum of Higher Education for Postsecondary Students
With Intellectual Disabilities.
AB - Students with intellectual and/or developmental disabilities (IDD) increasingly
pursue postsecondary education (PSE). Navigating the hidden curriculum-including
meeting prerequisites for PSE and employment, using support systems and community
transportation, and carrying out adulthood expectations-is an area of challenge.
This exploratory case study examined experiences of students with IDD attending a
PSE program and stakeholder perspectives. Thirty-two participants (10 students
with IDD, 5 parents or guardians, 4 college administrators, 8 college
instructors, 4 occupational therapists, and a transition specialist) were
interviewed. Conventional content analysis revealed navigating the hidden
curriculum as a key theme and three subthemes: (1) adult-based system navigation,
(2) persisting challenges with adaptive behaviors, and (3) disability awareness
and disclosure. Limited awareness of disability and supports and services needed
for a successful PSE outcome were contributing factors. Occupational therapists
have the skills to support students with IDD in skill acquisition to successfully
transition to and navigate PSE and the hidden curriculum.
PMID- 28422627
TI - Quality of Life Perspectives of People With Amyotrophic Lateral Sclerosis and
Their Caregivers.
AB - This study explored differences in perspectives on quality of life (QOL) between
people affected by amyotrophic lateral sclerosis (ALS) and their caregivers. QOL
is often thought of as related to physical limitations, without consideration of
other factors (e.g., cognitive, emotional) that may be stronger predictors of QOL
in people with long-term degenerative diseases. Because QOL is complex and
influenced by multiple factors, people with ALS and their caregivers may have
different perspectives on what constitutes QOL. This study investigated potential
discrepancies in QOL perspectives between people with ALS and their caregivers.
Thirty dyads from the Augusta University Health ALS Clinic completed a measure of
QOL, and we compared the results and identified patterns. The most prominent
finding was that members of the dyads misunderstood the mental experiences of one
another.
PMID- 28422628
TI - Occupational Performance Coaching for Stroke Survivors: A Pilot Randomized
Controlled Trial.
AB - OBJECTIVE: We examined the feasibility of study procedures and explored the
potential efficacy of Occupational Performance Coaching for stroke survivors (OPC
Stroke), an intervention designed to improve participation after stroke. METHOD:
In this pilot randomized controlled trial, 21 participants were randomized to
receive the intervention or usual care. Recruitment, retention, and outcome
completion rates were calculated. Direction of change and effect sizes were
examined for the outcomes of participation, goal performance and satisfaction,
goal self-efficacy, emotional well-being, and cognition. RESULTS: Rates of
recruitment (66%) and retention (81%) were satisfactory. Participation scores
improved for both groups with different trajectories. Results showed a moderate
effect of OPC-Stroke for goal performance (eta2partial d = .075) and satisfaction
(eta2partial d = .078) and a large effect for cognition (eta2partial d = .167).
Other outcome measures did not change as expected. CONCLUSION: Study procedures
were generally feasible. Preliminary findings support testing to examine the
efficacy of OPC-Stroke.
PMID- 28422629
TI - Development and Alternate Form Reliability of the Complex Task Performance
Assessment (CTPA) for People With Mild Stroke.
AB - Cognitive impairment is a common consequence of mild stroke. Current performance
based assessments for mild stroke can detect mild impairments in executive
function but lack alternate forms to be used as outcome measures. This study
aimed to develop an alternate form of the Complex Task Performance Assessment
(CTPA-Alt), a performance-based assessment of executive function, and to
establish the alternate form reliability of the CTPA-Alt. A repeated-measures
study was conducted with 26 community participants. Participants were screened
for eligibility and administered both forms of the CTPA; administration order was
alternated. Overall performance was significantly correlated (rs = .44, p = .03),
but pattern of scoring differed by CTPA form and order of administration. Our
results indicate that the CTPA forms were similar but that the specific tasks in
each form were different. The CTPA may be used as an ecologically valid outcome
assessment with further considerations.
PMID- 28422630
TI - Feasibility of Pediatric Game-Based Neurorehabilitation Using Telehealth
Technologies: A Case Report.
AB - This case report is the first in a series of reports designed to determine the
feasibility of implementing game-based neurorehabilitation using telehealth
technologies (GbN+TT) for children with cerebral palsy, evaluate the
responsiveness of relevant outcome measures to changes in motor impairment and
activity participation after intervention, and identify technological challenges
associated with implementation of GbN+TT. The participant completed more than 56
hr of game-based neurorehabilitation over 8 wk using the Timocco platform in his
home. The primary measures of motor impairment (Bruininks-Oseretsky Test of Motor
Proficiency, Second Edition) and function (Pediatric Motor Activity Log) were
both sensitive to change. Results indicate that it is feasible to administer
GbN+TT to a child with cerebral palsy and monitor outcomes using standardized
assessments.
PMID- 28422631
TI - Do Neglect Assessments Detect Neglect Differently?
AB - OBJECTIVE: We determined whether various assessment tools detect neglect
differently by administering a battery of assessments to people with stroke.
METHOD: We conducted a case series study and administered five neglect
assessments (paper-and-pencil, functional, virtual reality) to participants
poststroke. RESULTS: Twelve participants (6 men, 6 women) with stroke completed
the assessment battery, which required approximately 2 hr to administer (over one
to two sessions). All participants demonstrated neglect on three or more
assessments. Functional assessments and the virtual reality assessment detected
neglect more frequently than the paper-and-pencil assessments. Participants
performed differently on the paper-and-pencil assessments and functional
assessments. CONCLUSION: Because neglect is complex, detection may depend largely
on the assessment administered.
PMID- 28422632
TI - Somatosensory Discrimination Intervention Improves Body Position Sense and Motor
Performance in Children With Hemiplegic Cerebral Palsy.
AB - OBJECTIVE: This study examined the use of the adult neuroscience-based Sense(c)
intervention with children with hemiplegic cerebral palsy (HCP) to improve upper
limb somatosensory discrimination, motor function, and goal performance. METHOD:
Seventeen children with HCP (9 boys, 8 girls; mean age = 10.2 yr) participated in
this pilot matched-pairs trial with random allocation and 6-mo follow-up
(intervention, n = 7; control, n = 10). The intervention group received Sense
training 3*/wk for 6 wk (18 hr). Outcome measures included Goal Attainment
Scaling, Sense_assess(c) Kids, and the Assisting Hand Assessment. RESULTS: The
intervention group improved in goal performance, proprioception, and bimanual
hand use and maintained improvement at 6-mo follow-up. The control group improved
in occupational performance by 6-mo follow-up. CONCLUSION: This study established
the feasibility of using the Sense intervention in a pediatric setting and adds
preliminary evidence to suggest that improving somatosensory function can improve
motor function and goal performance among children with HCP.
PMID- 28422633
TI - Change in Functional Arm Use Is Associated With Somatosensory Skills After
Sensory Retraining Poststroke.
AB - OBJECTIVE: We investigated changes in functional arm use after retraining for
stroke-related somatosensory loss and identified whether such changes are
associated with somatosensory discrimination skills. METHOD: Data were pooled (N
= 80) from two randomized controlled trials of somatosensory retraining. We used
the Motor Activity Log to measure perceived amount of arm use in daily activities
and the Action Research Arm Test to measure performance capacity. Somatosensory
discrimination skills were measured using standardized modality-specific
measures. RESULTS: Participants' arm use improved after somatosensory retraining
(z = -6.80, p < .01). Change in arm use was weakly associated with
somatosensation (tactile, beta = 0.31, p < .01; proprioception, beta = -0.17, p >
.05; object recognition, beta = 0.13, p < .05). CONCLUSION: Change in daily arm
use was related to a small amount of variance in somatosensory outcomes. Stroke
survivors' functional arm use can increase after somatosensory retraining, with
change varying among survivors.
PMID- 28422634
TI - Functional Brain Stimulation in a Chronic Stroke Survivor With Moderate
Impairment.
AB - OBJECTIVE: To determine the impact of transcranial direct current stimulation
(tDCS) combined with repetitive, task-specific training (RTP) on upper-extremity
(UE) impairment in a chronic stroke survivor with moderate impairment. METHOD:
The participant was a 54-yr-old woman with chronic, moderate UE hemiparesis after
a single stroke that had occurred 10 yr before study enrollment. She participated
in 45-min RTP sessions 3 days/wk for 8 wk. tDCS was administered concurrent to
the first 20 min of each RTP session. RESULTS: Immediately after intervention,
the participant demonstrated marked score increases on the UE section of the Fugl
Meyer Scale and the Motor Activity Log (on both the Amount of Use and the Quality
of Movement subscales). CONCLUSION: These data support the use of tDCS combined
with RTP to decrease impairment and increase UE use in chronic stroke patients
with moderate impairment. This finding is crucial, given the paucity of
efficacious treatment approaches in this impairment level.
PMID- 28422635
TI - Simulated Driving Skills Evaluation of Teenagers With Attention Deficit
Hyperactivity Disorder Before Driving Lessons.
AB - OBJECTIVE: We evaluated the driving skills of teenagers with attention deficit
hyperactivity disorder (ADHD) during simulated driving before starting driving
lessons and observed whether methylphenidate (MPH) affected their performance.
METHOD: Sixty teenagers ages 15-18 yr were included; 29 teenagers with ADHD were
tested with and without MPH, and 31 teenagers (control group) were tested once.
All participants were tested on the STISIM DriveTM simulator. RESULTS: The number
of center-line crossings was higher in the group without MPH treatment than in
the control group and the MPH-treated group. The group without MPH treatment had
more road-edge excursions compared with the control group and drove faster than
the MPH-treated group. CONCLUSION: Adolescents with ADHD without MPH treatment
demonstrated impaired performance more often while driving the simulator,
resembling characteristics found during on-road driving among teenagers with
ADHD. Trainer awareness is a primary intervention before taking driving lessons
to help teenagers achieve safe driving performance.
PMID- 28422636
TI - Impact of PANS and PANDAS Exacerbations on Occupational Performance: A Mixed
Methods Study.
AB - OBJECTIVE: Pediatric acute-onset neuropsychiatric syndrome (PANS) includes
pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections and involves sudden-onset neuropsychiatric symptoms, including
obsessions, compulsions, sensory difficulties, and dysgraphia after infection or
other triggers. Our objective was to identify problems with areas of occupation,
body functions, and performance skills during exacerbations. METHOD: In this
online retrospective study, based on the Occupational Therapy Practice Framework:
Domain and Process (2nd ed.), we surveyed parents of 111 children with PANS.
RESULTS: Activities of daily living, math, handwriting, extracurricular
activities, free play, organized sports, community and family social
participation, higher level thinking, attention, memory, sequencing, emotional
coping, and energy and drive were commonly affected during exacerbations. During
exacerbations, children often required assistance and adaptation to remain
functional or were unable to function at a typical level. CONCLUSION: Children
with PANS present with pervasive occupational performance needs during
exacerbation. Children and families may benefit from accommodations to maximize
function during this turbulent period.
PMID- 28422637
TI - Embedding Questions During Online Lecture Capture to Promote Learning and
Transfer of Knowledge.
AB - We examined the effect of quizzing on students' ability to apply lecture content
to clinical examples on an in-class exam. Fifty-six occupational therapy students
in a graduate-level course completed three online modules that included lectures,
slide presentations, demonstrations, and video clips. Throughout each module,
students were given "Learning Moments," in which they were asked a question
(Question condition); were asked to read a statement confirming the content
presented (Study condition); or were not asked to do anything (Not Asked
condition). The Question condition resulted in better exam performance than the
combined Study and Not Asked conditions (p < .01), whereas performance on Study
and Not Asked questions did not differ (p = .67). Students performed better on
material on which they had been previously quizzed (i.e., testing effect).
Quizzing may be a good strategy to prepare students for clinical practice.
PMID- 28422638
TI - Resource Seeking as Occupation: A Critical and Empirical Exploration.
AB - Occupational therapists and occupational scientists are committed to generating
and using knowledge about occupation, but Western middle-class social norms
regarding particular ways of doing have limited explorations of survival
occupations. This article provides empirical evidence of the ways in which
resource seeking constitutes an occupational response to situations of uncertain
survival. Resource seeking includes a range of activities outside formal
employment that aim to meet basic needs. On the basis of findings from 2
ethnographic studies, we critique the presumption of survival in guiding
occupational therapy documents and the accompanying failure to recognize
occupations that seem at odds with self-sufficiency. We argue that failing to
name resource seeking in occupational therapy documents risks alignment with
social, political, and economic trends that foster occupational injustices. If
occupational therapists truly aim to meet society's occupational needs, they must
ensure that professional documents and discourses reflect the experiences of all
people in society.
PMID- 28422639
TI - Rehabilitation Research at the National Institutes of Health: Moving the Field
Forward (Executive Summary).
AB - Approximately 53 million Americans live with a disability. For decades, the
National Institutes of Health (NIH) has been conducting and supporting research
to discover new ways to minimize disability and enhance the quality of life of
people with disabilities. After the passage of the Americans With Disabilities
Act, NIH established the National Center for Medical Rehabilitation Research,
with the goal of developing and implementing a rehabilitation research agenda.
Currently, 17 institutes and centers at NIH invest more than $500 million per
year in rehabilitation research. Recently, the director of NIH, Francis Collins,
appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research
across institutes and centers. As a follow-up to the work of that panel, NIH
recently organized a conference, "Rehabilitation Research at NIH: Moving the
Field Forward." This report is a summary of the discussions and proposals that
will help guide rehabilitation research at NIH in the near future.
PMID- 28422640
TI - National Institutes of Health Research Plan on Rehabilitation.
AB - One in 5 Americans experiences disability that affects daily function because of
impairments in mobility, impairments in cognitive function, sensory impairment,
or communication impairment. The need for rehabilitation strategies to optimize
function and reduce disability is a clear priority for research to address this
public health challenge. The National Institutes of Health (NIH) recently
published a Research Plan on Rehabilitation that provides a set of priorities to
guide the field over the next 5 years. The plan was developed with input from
multiple institutes and centers within the NIH, the National Advisory Board for
Medical Rehabilitation Research, and the public. This article provides an
overview of the need for this research plan, an outline of its development, and a
listing of six priority areas for research.
PMID- 28422641
TI - Supporting Stroke Motor Recovery Through a Mobile Application: A Pilot Study.
AB - Neuroplasticity and motor learning are promoted with repetitive movement,
appropriate challenge, and performance feedback. ARMStrokes, a smartphone
application, incorporates these qualities to support motor recovery. Engaging
exercises are easily accessible for improved compliance. In a multiple-case,
mixed-methods pilot study, the potential of this technology for stroke motor
recovery was examined. Exercises calibrated to the participant's skill level
targeted forearm, elbow, and shoulder motions for a 6-wk protocol. Visual,
auditory, and vibration feedback promoted self-assessment. Pre- and posttest data
from 6 chronic stroke survivors who used the app in different ways (i.e., to
measure active or passive motion, to track endurance) demonstrated improvements
in accuracy of movements, fatigue, range of motion, and performance of daily
activities. Statistically significant changes were not obtained with this pilot
study. Further study on the efficacy of this technology is supported.
PMID- 28422642
TI - Detection and Treatment of Autism Spectrum Disorder by Occupational Therapy
Practitioners: Addressing Racial Disparity in Diagnosis.
AB - As the prevalence of autism spectrum disorder (ASD) continues to rise, racial
disparities remain in age of diagnosis and initiation of treatment. Therefore,
occupational therapy practitioners should examine cultural perceptions related to
disparities in ASD diagnosis. This article investigates the role that
practitioners may play in this disparity by asking, "Are occupational therapy
practitioners contributing to the late diagnosis of children with ASD who are
members of particular racial or ethnic groups?" Correlations among practitioners'
detection of symptoms, parents' perceptions, and evaluator influences are
investigated. By examining these factors, practitioners may gain better insight
into these disparities and therefore provide more effective advocacy regarding
early diagnosis and treatment access.
PMID- 28422643
TI - Occupational Therapy Interventions for Adults With Traumatic Brain Injury.
AB - This Evidence Connection describes a case report of an adult with traumatic brain
injury (TBI), applying the evidence for intervention from the systematic reviews
on TBI that were conducted in conjunction with the American Occupational Therapy
Association's (AOTA's) Evidence-Based Practice Project. The occupational therapy
assessment and treatment processes for hospital, home, and community settings are
described. Evidence Connection articles provide a clinical application of
systematic reviews developed in conjunction with AOTA's Evidence-Based Practice
Project.
PMID- 28422644
TI - Vision 2025.
PMID- 28422647
TI - EEG-Based Affect and Workload Recognition in a Virtual Driving Environment for
ASD Intervention.
AB - OBJECTIVE: To build group-level classification models capable of recognizing
affective states and mental workload of individuals with autism spectrum disorder
(ASD) during driving skill training. METHODS: Twenty adolescents with ASD
participated in a six-session virtual reality driving simulator-based experiment,
during which their electroencephalogram (EEG) data were recorded alongside
driving events and a therapist's rating of their affective states and mental
workload. Five feature generation approaches including statistical features,
fractal dimension features, higher order crossings (HOC)-based features, power
features from frequency bands, and power features from bins () were applied to
extract relevant features. Individual differences were removed with a two-step
feature calibration method. Finally, binary classification results based on the k
nearest neighbors algorithm and univariate feature selection method were
evaluated by leave-one-subject-out nested cross-validation to compare feature
types and identify discriminative features. RESULTS: The best classification
results were achieved using power features from bins for engagement (0.95) and
boredom (0.78), and HOC-based features for enjoyment (0.90), frustration (0.88),
and workload (0.86). CONCLUSION: Offline EEG-based group-level classification
models are feasible for recognizing binary low and high intensity of affect and
workload of individuals with ASD in the context of driving. However, while
promising the applicability of the models in an online adaptive driving task
requires further development. SIGNIFICANCE: The developed models provide a basis
for an EEG-based passive brain computer interface system that has the potential
to benefit individuals with ASD with an affect- and workload-based individualized
driving skill training intervention.
PMID- 28422646
TI - Coordinated control of terminal differentiation and restriction of cellular
plasticity.
AB - The acquisition of a specific cellular identity is usually paralleled by a
restriction of cellular plasticity. Whether and how these two processes are
coordinated is poorly understood. Transcription factors called terminal selectors
activate identity-specific effector genes during neuronal differentiation to
define the structural and functional properties of a neuron. To study restriction
of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of
ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE
1 results in activation of ASE neuron type-specific effector genes. Once cells
differentiate, their plasticity is restricted and ectopic expression of CHE-1 no
longer results in activation of ASE effector genes. In striking contrast, removal
of the respective terminal selectors of other sensory, inter-, or motor neuron
types now enables ectopically expressed CHE-1 to activate its ASE-specific
effector genes, indicating that terminal selectors not only activate effector
gene batteries but also control the restriction of cellular plasticity. Terminal
selectors mediate this restriction at least partially by organizing chromatin.
The chromatin structure of a CHE-1 target locus is less compact in neurons that
lack their resident terminal selector and genetic epistasis studies with H3K9
methyltransferases suggest that this chromatin modification acts downstream of a
terminal selector to restrict plasticity. Taken together, terminal selectors
activate identity-specific genes and make non-identity-defining genes less
accessible, thereby serving as a checkpoint to coordinate identity specification
with restriction of cellular plasticity.
PMID- 28422648
TI - Fast and Stable Signal Deconvolution via Compressible State-Space Models.
AB - OBJECTIVE: Common biological measurements are in the form of noisy convolutions
of signals of interest with possibly unknown and transient blurring kernels.
Examples include EEG and calcium imaging data. Thus, signal deconvolution of
these measurements is crucial in understanding the underlying biological
processes. The objective of this paper is to develop fast and stable solutions
for signal deconvolution from noisy, blurred, and undersampled data, where the
signals are in the form of discrete events distributed in time and space.
METHODS: We introduce compressible state-space models as a framework to model and
estimate such discrete events. These state-space models admit abrupt changes in
the states and have a convergent transition matrix, and are coupled with
compressive linear measurements. We consider a dynamic compressive sensing
optimization problem and develop a fast solution, using two nested expectation
maximization algorithms, to jointly estimate the states as well as their
transition matrices. Under suitable sparsity assumptions on the dynamics, we
prove optimal stability guarantees for the recovery of the states and present a
method for the identification of the underlying discrete events with precise
confidence bounds. RESULTS: We present simulation studies as well as application
to calcium deconvolution and sleep spindle detection, which verify our
theoretical results and show significant improvement over existing techniques.
CONCLUSION: Our results show that by explicitly modeling the dynamics of the
underlying signals, it is possible to construct signal deconvolution solutions
that are scalable, statistically robust, and achieve high temporal resolution.
SIGNIFICANCE: Our proposed methodology provides a framework for modeling and
deconvolution of noisy, blurred, and undersampled measurements in a fast and
stable fashion, with potential application to a wide range of biological data.
PMID- 28422649
TI - Visual Servoed Three-Dimensional Rotation Control in Zebrafish Larva Heart
Microinjection System.
AB - OBJECTIVE: Zebrafish larva heart microinjection is a widely used technique in
cardiac disease study. Compared with intensively researched rotation control of
spherical or nearly spherical targets with clear structures, such as cells and
embryos, 3-D rotation control of zebrafish larva demands new techniques due to
its nontransparent structures and irregular outlines. METHODS: In this paper, we
present a vision-servo system to automate the rotation process of zebrafish larva
body. A switched control strategy is adopted to rotate zebrafish larva about the
optical axis by using two micropipettes. Precisely rolling about larva body is
performed, which involves a custom-designed rotational micromanipulator. A vision
detection and online tracking algorithm is also developed to meet the requirement
of visual servoing. With designed rotation control strategy, zebrafish larva
heart can be adjusted to a desired orientation, which is often towards the
injection pipette tip. RESULTS: Experimental results show that the designed
system is capable of achieving high success rate of 94% about -axis rotation and
100% about -axis with 50 trails. The system also performs an average speed of 44
s/larva with a satisfied rotation accuracy of 0.5 in the horizontal plane and 2.5
about its roll axis. CONCLUSION: The proposed strategy is effective in flexibly
manipulating larvae in 3-D. SIGNIFICANCE: The developed 3-D rotation control
scheme is able to be applied to injection of various organs in zebrafish larva
body for different experimental requirements.
PMID- 28422650
TI - Joint Magnetic Calibration and Localization Based on Expectation Maximization for
Tongue Tracking.
AB - BACKGROUND: Tongue tracking, which helps researchers gain valuable insights into
speech mechanism, has many applications in speech therapy and language learning.
The wireless localization technique, which involves tracking a small magnetic
tracer within the 3-D oral space, provides a low cost and convenient approach to
capture tongue kinematics. In practice, this technique requires accurate
calibration of three-axial magnetic sensors used in the tracking system. The data
driven calibration depends on the trajectories of magnetic tracer and the ambient
noise, which may change across time and space. METHODS: In this paper, we model
the kinematics of tracer movement and the noisy magnetic measurements in a
Bayesian framework, then present a joint calibration and localization (JCL)
algorithm based on expectation maximization (EM), where the unscented Rauch-Tung
Striebel smoother is employed for tracer localization and the curvilinear search
algorithm is applied for sensor calibration. RESULTS: Based on measurements
conducted on our tongue tracking system with a small magnetic tracer (diameter:
6.05 mm, thickness: 1.25 mm, residual induction: 14 800 G), the JCL algorithm
achieves averaged root mean square error of 0.45 mm for tracer position
estimation and for tracer orientation estimation, which are significantly lower
than those of the separate calibration and localization algorithms. CONCLUSION:
These results show that JCL can help improve the localization accuracy of this
system. SIGNIFICANCE: A potentially high precision tongue tracking method is
demonstrated.
PMID- 28422651
TI - Direct Sparse Odometry.
AB - Direct Sparse Odometry (DSO) is a visual odometry method based on a novel, highly
accurate sparse and direct structure and motion formulation. It combines a fully
direct probabilistic model (minimizing a photometric error) with consistent,
joint optimization of all model parameters, including geometry-represented as
inverse depth in a reference frame-and camera motion. This is achieved in real
time by omitting the smoothness prior used in other direct methods and instead
sampling pixels evenly throughout the images. Since our method does not depend on
keypoint detectors or descriptors, it can naturally sample pixels from across all
image regions that have intensity gradient, including edges or smooth intensity
variations on essentially featureless walls. The proposed model integrates a full
photometric calibration, accounting for exposure time, lens vignetting, and non
linear response functions. We thoroughly evaluate our method on three different
datasets comprising several hours of video. The experiments show that the
presented approach significantly outperforms state-of-the-art direct and indirect
methods in a variety of real-world settings, both in terms of tracking accuracy
and robustness.
PMID- 28422652
TI - Robust Relative Rotation Averaging.
AB - This paper addresses the problem of robust and efficient relative rotation
averaging in the context of large-scale Structure from Motion. Relative rotation
averaging finds global or absolute rotations for a set of cameras from a set of
observed relative rotations between pairs of cameras. We propose a generalized
framework of relative rotation averaging that can use different robust loss
functions and jointly optimizes for all the unknown camera rotations. Our method
uses a quasi-Newton optimization which results in an efficient iteratively
reweighted least squares (IRLS) formulation that works in the Lie algebra of the
3D rotation group. We demonstrate the performance of our approach on a number of
large-scale data sets. We show that our method outperforms existing methods in
the literature both in terms of speed and accuracy.
PMID- 28422653
TI - Learning Compositional Sparse Bimodal Models.
AB - Various perceptual domains have underlying compositional semantics that are
rarely captured in current models. We suspect this is because directly learning
the compositional structure has evaded these models. Yet, the compositional
structure of a given domain can be grounded in a separate domain thereby
simplifying its learning. To that end, we propose a new approach to modeling
bimodal perceptual domains that explicitly relates distinct projections across
each modality and then jointly learns a bimodal sparse representation. The
resulting model enables compositionality across these distinct projections and
hence can generalize to unobserved percepts spanned by this compositional basis.
For example, our model can be trained on red triangles and blue squares; yet,
implicitly will also have learned red squares and blue triangles. The structure
of the projections and hence the compositional basis is learned automatically; no
assumption is made on the ordering of the compositional elements in either
modality. Although our modeling paradigm is general, we explicitly focus on a
tabletop building-blocks setting. To test our model, we have acquired a new
bimodal dataset comprising images and spoken utterances of colored shapes
(blocks) in the tabletop setting. Our experiments demonstrate the benefits of
explicitly leveraging compositionality in both quantitative and human evaluation
studies.
PMID- 28422654
TI - Novel MRI Technique Enables Non-Invasive Measurement of Atrial Wall Thickness.
AB - Knowledge of atrial wall thickness (AWT) has the potential to provide important
information for patient stratification and the planning of interventions in
atrial arrhythmias. To date, information about AWT has only been acquired in post
mortem or poor-contrast computed tomography (CT) studies, providing limited
coverage and highly variable estimates of AWT. We present a novel contrast agent
free MRI sequence for imaging AWT and use it to create personalized AWT maps and
a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol
was used to image ten volunteers and, as proof of concept, two atrial
fibrillation patients. Both atria were manually segmented to create subject
specific AWT maps using an average of nearest neighbors approach. These were then
registered non-linearly to generate an AWT atlas. AWT was 2.4 +/- 0.7 and 2.7 +/-
0.7 mm in the left and right atria, respectively, in good agreement with post
mortem and CT data, where available. AWT was 2.6 +/- 0.7 mm in the left atrium of
a patient without structural heart disease, similar to that of volunteers. In a
patient with structural heart disease, the AWT was increased to 3.1 +/- 1.3 mm.
We successfully designed an MRI protocol to non-invasively measure AWT and create
the first whole-atria AWT atlas. The atlas can be used as a reference to study
alterations in thickness caused by atrial pathology. The protocol can be used to
acquire personalized AWT maps in a clinical setting and assist in the treatment
of atrial arrhythmias.
PMID- 28422655
TI - Validation of a Regression Technique for Segmentation of White Matter
Hyperintensities in Alzheimer's Disease.
AB - Segmentation and volumetric quantification of white matter hyperintensities
(WMHs) is essential in assessment and monitoring of the vascular burden in aging
and Alzheimer's disease (AD), especially when considering their effect on
cognition. Manually segmenting WMHs in large cohorts is technically unfeasible
due to time and accuracy concerns. Automated tools that can detect WMHs robustly
and with high accuracy are needed. Here, we present and validate a fully
automatic technique for segmentation and volumetric quantification of WMHs in
aging and AD. The proposed technique combines intensity and location features
frommultiplemagnetic resonance imaging contrasts and manually labeled training
data with a linear classifier to perform fast and robust segmentations. It
provides both a continuous subject specific WMH map reflecting different levels
of tissue damage and binary segmentations. Themethodwas used to detectWMHs in 80
elderly/AD brains (ADC data set) as well as 40 healthy subjects at risk of AD
(PREVENT-AD data set). Robustness across different scanners was validated using
ten subjects from ADNI2/GO study. Voxel-wise and volumetric agreements were
evaluated using Dice similarity index (SI) and intra-class correlation (ICC),
yielding ICC=0.96 , SI = 0.62+/-0.16 for ADC data set and ICC=0.78 , SI=0.51+/
0.15 for PREVENT-AD data set. The proposed method was robust in the independent
sample yielding SI=0.64+/-0.17 with ICC=0.93 for ADNI2/GO subjects. The proposed
method provides fast, accurate, and robust segmentations on previously unseen
data from different models of scanners, making it ideal to study WMHs in large
scale multi-site studies.
PMID- 28422656
TI - Fast Plane Wave 2-D Vector Flow Imaging Using Transverse Oscillation and
Directional Beamforming.
AB - Several techniques can estimate the 2-D velocity vector in ultrasound.
Directional beamforming (DB) estimates blood flow velocities with a higher
precision and accuracy than transverse oscillation (TO), but at the cost of a
high beamforming load when estimating the flow angle. In this paper, it is
proposed to use TO to estimate an initial flow angle, which is then refined in a
DB step. Velocity magnitude is estimated along the flow direction using cross
correlation. It is shown that the suggested TO-DB method can improve the
performance of velocity estimates compared with TO, and with a beamforming load,
which is 4.6 times larger than for TO and seven times smaller than for
conventional DB. Steered plane wave transmissions are employed for high frame
rate imaging, and parabolic flow with a peak velocity of 0.5 m/s is simulated in
straight vessels at beam-to-flow angles from 45 degrees to 90 degrees . The TO
DB method estimates the angle with a bias and standard deviation (SD) less than 2
degrees , and the SD of the velocity magnitude is less than 2%. When using only
TO, the SD of the angle ranges from 2 degrees to 17 degrees and for the
velocity magnitude up to 7%. Bias of the velocity magnitude is within 2% for TO
and slightly larger but within 4% for TO-DB. The same trends are observed in
measurements although with a slightly larger bias. Simulations of realistic flow
in a carotid bifurcation model provide visualization of complex flow, and the
spread of velocity magnitude estimates is 7.1 cm/s for TO-DB, while it is 11.8
cm/s using only TO. However, velocities for TO-DB are underestimated at peak
systole as indicated by a regression value of 0.97 for TO and 0.85 for TO-DB. An
in vivo scanning of the carotid bifurcation is used for vector velocity
estimations using TO and TO-DB. The SD of the velocity profile over a cardiac
cycle is 4.2% for TO and 3.2% for TO-DB.
PMID- 28422657
TI - Phased Array Ultrasound System for Planar Flow Mapping in Liquid Metals.
AB - Controllable magnetic fields can be used to optimize flows in technical and
industrial processes involving liquid metals in order to improve quality and
yield. However, experimental studies in magnetohydrodynamics often involve
complex, turbulent flows and require planar, two-component (2c) velocity
measurements through only one acoustical access. We present the phased array
ultrasound Doppler velocimeter as a modular research platform for flow mapping in
liquid metals. It combines the pulse wave Doppler method with the phased array
technique to adaptively focus the ultrasound beam. This makes it possible to
resolve smaller flow structures in planar measurements compared with fixed-beam
sensors and enables 2c flow mapping with only one acoustical access via the cross
beam technique. From simultaneously measured 2-D velocity fields, quantities for
turbulence characterization can be derived. The capabilities of this measurement
system are demonstrated through measurements in the alloy gallium-indium-tin at
room temperature. The 2-D, 2c velocity measurements of a flow in a cubic vessel
driven by a rotating magnetic field (RMF) with a spatial resolution of up to 2.2
mm are presented. The measurement results are in good agreement with a
semianalytical simulation. As a highlight, two-point correlation functions of the
velocity field for different magnitudes of the RMF are presented.
PMID- 28422658
TI - Equivalent Magnetic Noise in Magnetoelectric Laminates Comprising Bidomain LiNbO3
Crystals.
AB - The anisotropic direct magnetoelectric (ME) properties of bilayered composites
comprising magnetostrictive metglas foils and single-crystalline piezoelectric
bidomain plates of 127 degrees Y-cut LiNbO3 (LNO) have been studied theoretically
and experimentally. The LNO plates possessed an engineered ferroelectric
macrobidomain structure with opposite spontaneous polarization vectors.
Impedance, ME effect, and equivalent magnetic noise density (EMND) measurements
have been performed under quasi-static and resonant conditions. Whereas the quasi
static ME effect was only two times stronger in the bidomain samples compared to
their unidomain and bonded bimorph counterparts, in the bending resonance mode,
the effect was up to one order of magnitude stronger: ME coefficients of up to
578 V/( [Formula: see text]) were obtained at ca. 30 kHz under resonance using
0.5-mm-thick crystals. EMND measurements yielded values down to 153 pT/Hz 1/2 at
1 kHz and 524 fT/Hz 1/2 under resonant conditions. A further optimization of the
fabrication techniques, laminate geometry, and detection circuit is expected to
allow reducing these values down to at least 10 pT/Hz 1/2 and 250 fT/Hz 1/2 ,
respectively, and the resonance frequency by at least two orders of magnitude.
Such systems may thus find use in simple and sensitive, passive and stable, low
frequency and high-temperature vector magnetic field sensors.
PMID- 28422659
TI - Revisiting Co-Saliency Detection: A Novel Approach Based on Two-Stage Multi-View
Spectral Rotation Co-clustering.
AB - With the goal of discovering the common and salient objects from the given image
group, co-saliency detection has received tremendous research interest in recent
years. However, as most of the existing co-saliency detection methods are
performed based on the assumption that all the images in the given image group
should contain co-salient objects in only one category, they can hardly be
applied in practice, particularly for the large-scale image set obtained from the
Internet. To address this problem, this paper revisits the co-saliency detection
task and advances its development into a new phase, where the problem setting is
generalized to allow the image group to contain objects in arbitrary number of
categories and the algorithms need to simultaneously detect multi-class co
salient objects from such complex data. To solve this new challenge, we decompose
it into two sub-problems, i.e., how to identify subgroups of relevant images and
how to discover relevant co-salient objects from each subgroup, and propose a
novel co-saliency detection framework to correspondingly address the two sub
problems via two-stage multi-view spectral rotation co-clustering. Comprehensive
experiments on two publically available benchmarks demonstrate the effectiveness
of the proposed approach. Notably, it can even outperform the state-of-the-art co
saliency detection methods, which are performed based on the image subgroups
carefully separated by the human labor.
PMID- 28422660
TI - Weak Classifier for Density Estimation in Eye Localization and Tracking.
AB - In this paper, we propose a fast weak classifier that can detect and track eyes
in video sequences. The approach relies on a least-squares detector based on the
inner product detector (IPD) that can stimate a probability density distribution
for a feature's location-which fits naturally with a Bayesian estimation cycle,
such as a Kalman or particle filter. As a least-squares sliding window detector,
it possesses tolerance to small variations in the desired pattern while
maintaining good generalization capabilities and computational efficiency. We
propose two approaches to integrating the IPD with a particle filter tracker. We
use the BioID, FERET, LFPW, and COFW public datasets as well as five manually
annotated high-definition video sequences to quantitatively evaluate the
algorithms' performance. The video data set contains four subjects, different
types of backgrounds, blurring due to fast motion, and occlusions. All code and
data are available.
PMID- 28422661
TI - Correlated Topic Vector for Scene Classification.
AB - Scene images usually involve semantic correlations, particularly when considering
large-scale image data sets. This paper proposes a novel generative image
representation, correlated topic vector, to model such semantic correlations.
Oriented from the correlated topic model, correlated topic vector intends to
naturally utilize the correlations among topics, which are seldom considered in
the conventional feature encoding, e.g., Fisher vector, but do exist in scene
images. It is expected that the involvement of correlations can increase the
discriminative capability of the learned generative model and consequently
improve the recognition accuracy. Incorporated with the Fisher kernel method,
correlated topic vector inherits the advantages of Fisher vector. The
contributions to the topics of visual words have been further employed by
incorporating the Fisher kernel framework to indicate the differences among
scenes. Combined with the deep convolutional neural network (CNN) features and
Gibbs sampling solution, correlated topic vector shows great potential when
processing large-scale and complex scene image data sets. Experiments on two
scene image data sets demonstrate that correlated topic vector improves
significantly the deep CNN features, and outperforms existing Fisher kernel-based
features.
PMID- 28422662
TI - Use of Accelerometers in the Control of Practical Prosthetic Arms.
AB - Accelerometers can be used to augment the control of powered prosthetic arms.
They can detect the orientation of the joint and limb, and the controller can
correct for the amount of torque required to move the limb. They can also be used
to create a platform, with a fixed orientation relative to gravity for the object
held in the hand. This paper describes three applications for this technology, in
a powered wrist and powered arm. By adding sensors to the arm making these data
available to the controller, the input from the user can be made simpler. The
operator will not need to correct for changes in orientation of their body as
they move. Two examples of the correction for orientation against gravity are
described and an example of the system designed for use by a patient. The
controller for all examples is a distributed set of microcontrollers, one node
for each joint, linked with the control area network bus. The clinical arm uses a
version of the Southampton adaptive manipulation scheme to control the arm and
hand. In this control form, the user gives simpler input commands and leaves the
detailed control of the arm to the controller.
PMID- 28422663
TI - A Neural Probe With Up to 966 Electrodes and Up to 384 Configurable Channels in
0.13 $?mu$m SOI CMOS.
AB - In vivo recording of neural action-potential and local-field-potential signals
requires the use of high-resolution penetrating probes. Several international
initiatives to better understand the brain are driving technology efforts towards
maximizing the number of recording sites while minimizing the neural probe
dimensions. We designed and fabricated (0.13- MUm SOI Al CMOS) a 384-channel
configurable neural probe for large-scale in vivo recording of neural signals. Up
to 966 selectable active electrodes were integrated along an implantable shank
(70 MUm wide, 10 mm long, 20 MUm thick), achieving a crosstalk of [Formula: see
text] dB. The probe base (5 * 9 mm 2 ) implements dual-band recording and a 171.6
Mbps digital interface. Measurement results show a total input-referred noise of
6.4 MU V rms and a total power consumption of 49.1 MUW/channel.
PMID- 28422664
TI - Diaper-Embedded Urinary Tract Infection Monitoring Sensor Module Powered by Urine
Activated Batteries.
AB - Urinary tract infection (UTI) is one of the most common infections in humans. UTI
is easily treatable using antibiotics if identified in early stage. However,
without early identification and treatment, UTI can be a major source of serious
complications in geriatric patients, in particular, those suffering from
neurodegenerative diseases. Also, for infants who have difficulty in describing
their symptoms, UTI may lead to serious development of the disease making early
identification of UTI crucial. In this paper, we present a diaper-embedded,
wireless, self-powered, and autonomous UTI monitoring sensor module that allows
an early detection of UTI with minimal effort. The sensor module consists of a
paper-based colorimetric nitrite sensor, urine-activated batteries, a boost dc-dc
converter, a low-power sensor interface utilizing pulse width modulation, and a
Bluetooth low energy module for wireless transmission. Experimental results show
a better detection of nitrite, a surrogate of UTI, than that of conventional
dipstick testing. The proposed sensor module achieves a sensitivity of 1.35
ms/(mg/L) and a detection limit of 4 mg/L for nitrite.
PMID- 28422665
TI - Human Factors and Neurophysiological Metrics in Air Traffic Control: A Critical
Review.
AB - This paper provides a focused and organized review of the research progress on
neurophysiological indicators, also called "neurometrics," to show how they can
effectively address some of the most important human factors (HFs) needs in the
air traffic management (ATM) field. In order to better understand and highlight
available opportunities of such neuroscientific applications, state of the art on
the most involved HFs and related cognitive processes (e.g., mental workload and
cognitive training) are presented together with examples of possible applications
in current and future ATM scenarios. Furthermore, this paper will discuss the
potential enhancements that further research and development activities could
bring to the efficiency and safety of the ATM service.
PMID- 28422666
TI - Efficient kNN Classification With Different Numbers of Nearest Neighbors.
AB - nearest neighbor (kNN) method is a popular classification method in data mining
and statistics because of its simple implementation and significant
classification performance. However, it is impractical for traditional kNN
methods to assign a fixed value (even though set by experts) to all test samples.
Previous solutions assign different values to different test samples by the cross
validation method but are usually time-consuming. This paper proposes a kTree
method to learn different optimal values for different test/new samples, by
involving a training stage in the kNN classification. Specifically, in the
training stage, kTree method first learns optimal values for all training samples
by a new sparse reconstruction model, and then constructs a decision tree
(namely, kTree) using training samples and the learned optimal values. In the
test stage, the kTree fast outputs the optimal value for each test sample, and
then, the kNN classification can be conducted using the learned optimal value and
all training samples. As a result, the proposed kTree method has a similar
running cost but higher classification accuracy, compared with traditional kNN
methods, which assign a fixed value to all test samples. Moreover, the proposed
kTree method needs less running cost but achieves similar classification
accuracy, compared with the newly kNN methods, which assign different values to
different test samples. This paper further proposes an improvement version of
kTree method (namely, k*Tree method) to speed its test stage by extra storing the
information of the training samples in the leaf nodes of kTree, such as the
training samples located in the leaf nodes, their kNNs, and the nearest neighbor
of these kNNs. We call the resulting decision tree as k*Tree, which enables to
conduct kNN classification using a subset of the training samples in the leaf
nodes rather than all training samples used in the newly kNN methods. This
actually reduces running cost of test stage. Finally, the experimental results on
20 real data sets showed that our proposed methods (i.e., kTree and k*Tree) are
much more efficient than the compared methods in terms of classification tasks.
PMID- 28422667
TI - Modeling and Analysis of Beta Oscillations in the Basal Ganglia.
AB - Enhanced beta (12-30 Hz) oscillatory activity in the basal ganglia (BG) is a
prominent feature of the Parkinsonian state in animal models and in patients with
Parkinson's disease. Increased beta oscillations are associated with severe
dopaminergic striatal depletion. However, the mechanisms underlying these
pathological beta oscillations remain elusive. Inspired by the experimental
observation that only subsets of neurons within each nucleus in the BG exhibit
oscillatory activities, a computational model of the BG-thalamus neuronal network
is proposed, which is characterized by subdivided nuclei within the BG. Using
different currents externally applied to the neurons within a given nucleus,
neurons behave according to one of the two subgroups, named "-N" and "-P," where
"-N" and "-P" denote the normal and the Parkinsonian states, respectively. The
ratio of "-P" to "-N" neurons indicates the degree of the Parkinsonian state.
Simulation results show that if "-P" neurons have a high degree of connectivity
in the subthalamic nucleus (STN), they will have a significant downstream effect
on the generation of beta oscillations in the globus pallidus. Interestingly,
however, the generation of beta oscillations in the STN is independent of the
selection of the "-P" neurons in the external segment of the globus pallidus
(GPe), despite the reciprocal structure between STN and GPe. This computational
model may pave the way to revealing the mechanism of such pathological behaviors
in a realistic way that can replicate experimental observations. The simulation
results suggest that the STN is more suitable than GPe as a deep brain
stimulation target.
PMID- 28422668
TI - Sensitivity Analysis for Probabilistic Neural Network Structure Reduction.
AB - In this paper, we propose the use of local sensitivity analysis (LSA) for the
structure simplification of the probabilistic neural network (PNN). Three
algorithms are introduced. The first algorithm applies LSA to the PNN input layer
reduction by selecting significant features of input patterns. The second
algorithm utilizes LSA to remove redundant pattern neurons of the network. The
third algorithm combines the proposed two and constitutes the solution of how
they can work together. PNN with a product kernel estimator is used, where each
multiplicand computes a one-dimensional Cauchy function. Therefore, the smoothing
parameter is separately calculated for each dimension by means of the plug-in
method. The classification qualities of the reduced and full structure PNN are
compared. Furthermore, we evaluate the performance of PNN, for which global
sensitivity analysis (GSA) and the common reduction methods are applied, both in
the input layer and the pattern layer. The models are tested on the
classification problems of eight repository data sets. A 10-fold cross validation
procedure is used to determine the prediction ability of the networks. Based on
the obtained results, it is shown that the LSA can be used as an alternative PNN
reduction approach.
PMID- 28422669
TI - Bioinspired Approach to Modeling Retinal Ganglion Cells Using System
Identification Techniques.
AB - The processing capabilities of biological vision systems are still vastly
superior to artificial vision, even though this has been an active area of
research for over half a century. Current artificial vision techniques integrate
many insights from biology yet they remain far-off the capabilities of animals
and humans in terms of speed, power, and performance. A key aspect to modeling
the human visual system is the ability to accurately model the behavior and
computation within the retina. In particular, we focus on modeling the retinal
ganglion cells (RGCs) as they convey the accumulated data of real world images as
action potentials onto the visual cortex via the optic nerve. Computational
models that approximate the processing that occurs within RGCs can be derived by
quantitatively fitting the sets of physiological data using an input-output
analysis where the input is a known stimulus and the output is neuronal
recordings. Currently, these input-output responses are modeled using
computational combinations of linear and nonlinear models that are generally
complex and lack any relevance to the underlying biophysics. In this paper, we
illustrate how system identification techniques, which take inspiration from
biological systems, can accurately model retinal ganglion cell behavior, and are
a viable alternative to traditional linear-nonlinear approaches.
PMID- 28422670
TI - Observer-Based Robust Coordinated Control of Multiagent Systems With Input
Saturation.
AB - This paper addresses the robust semiglobal coordinated control of multiple-input
multiple-output multiagent systems with input saturation together with dead zone
and input additive disturbance. Observer-based coordinated control protocol is
constructed, by combining the parameterized low-and-high-gain feedback technique
and the high-gain observer design approach. It is shown that, under some mild
assumptions on agents' intrinsic dynamics, the robust semiglobal consensus or
robust semiglobal swarm can be approached for undirected connected multiagent
systems. Then, specific guidelines on the selection of the low-gain parameter,
the high-gain parameter, and the high-gain observer gain have been provided. At
last, numerical simulations are presented to illustrate the theoretical results.
PMID- 28422671
TI - Structured Learning of Tree Potentials in CRF for Image Segmentation.
AB - We propose a new approach to image segmentation, which exploits the advantages of
both conditional random fields (CRFs) and decision trees. In the literature, the
potential functions of CRFs are mostly defined as a linear combination of some
predefined parametric models, and then, methods, such as structured support
vector machines, are applied to learn those linear coefficients. We instead
formulate the unary and pairwise potentials as nonparametric forests-ensembles of
decision trees, and learn the ensemble parameters and the trees in a unified
optimization problem within the large-margin framework. In this fashion, we
easily achieve nonlinear learning of potential functions on both unary and
pairwise terms in CRFs. Moreover, we learn classwise decision trees for each
object that appears in the image. Experimental results on several public
segmentation data sets demonstrate the power of the learned nonlinear
nonparametric potentials.
PMID- 28422672
TI - AIIMDs: An Integrated Framework of Automatic Idiopathic Inflammatory Myopathy
Diagnosis for Muscle.
AB - Idiopathic inflammatory myopathy (IIM) is a common skeletal muscle disease that
relates to weakness and inflammation of muscle. Early diagnosis and prognosis of
different types of IIMs will guide the effective treatment. Interpretation of
digitized images of the cross-section muscle biopsy, which is currently done
manually, provides the most reliable diagnostic information. With the increasing
volume of images, the management and manual interpretation of the digitized
muscle images suffer from low efficiency and high interobserver variabilities. In
order to address these problems, we propose the first complete framework of
automatic IIM diagnosis system for the management and interpretation of digitized
skeletal muscle histopathology images. The proposed framework consists of several
key components: (1) Automatic cell segmentation, perimysium annotation, and
nuclei detection; (2) histogram-based feature extraction and quantification; (3)
content-based image retrieval to search and retrieve similar cases in the
database for comparative study; and (4) majority voting-based classification to
provide decision support for computer-aided clinical diagnosis. Experiments show
that the proposed diagnosis system provides efficient and robust interpretation
of the digitized muscle image and computer-aided diagnosis of IIM.
PMID- 28422673
TI - A Two-Phase Evolutionary Approach for Compressive Sensing Reconstruction.
AB - Sparse signal reconstruction can be regarded as a problem of locating the nonzero
entries of the signal. In presence of measurement noise, conventional methods
such as l1 norm relaxation methods and greedy algorithms, have shown their
weakness in finding the nonzero entries accurately. In order to reduce the impact
of noise and better locate the nonzero entries, in this paper, we propose a two
phase algorithm which works in a coarse-to-fine manner. In phase 1, a
decomposition-based multiobjective evolutionary algorithm is applied to generate
a group of robust solutions by optimizing l1 norm of the solutions. To remove the
interruption of noise, the statistical features with respect to each entry among
these solutions are extracted and an initial set of nonzero entries are
determined by clustering technique. In phase 2, a forward-based selection method
is proposed to further update this set and locate the nonzero entries more
precisely based on these features. At last, the magnitudes of the reconstructed
signal are obtained by the method of least squares. We conduct the comparison of
our proposed method with several state-of-the-art compressive sensing recover
methods, the best result in phase 1 and the approach combining phases 1 and 2
without the statistical features. Experimental results on benchmark signals as
well as randomly generated signals demonstrate that our proposed method
outperforms the above methods, achieving higher recover precision and maintaining
larger sparsity.
PMID- 28422674
TI - Incorporation of Efficient Second-Order Solvers Into Latent Factor Models for
Accurate Prediction of Missing QoS Data.
AB - Generating highly accurate predictions for missing quality-of-service (QoS) data
is an important issue. Latent factor (LF)-based QoS-predictors have proven to be
effective in dealing with it. However, they are based on first-order solvers that
cannot well address their target problem that is inherently bilinear and
nonconvex, thereby leaving a significant opportunity for accuracy improvement.
This paper proposes to incorporate an efficient second-order solver into them to
raise their accuracy. To do so, we adopt the principle of Hessian-free
optimization and successfully avoid the direct manipulation of a Hessian matrix,
by employing the efficiently obtainable product between its Gauss-Newton
approximation and an arbitrary vector. Thus, the second-order information is
innovatively integrated into them. Experimental results on two industrial QoS
datasets indicate that compared with the state-of-the-art predictors, the newly
proposed one achieves significantly higher prediction accuracy at the expense of
affordable computational burden. Hence, it is especially suitable for industrial
applications requiring high prediction accuracy of unknown QoS data.
PMID- 28422675
TI - Finite-Time Synchronization of Coupled Hierarchical Hybrid Neural Networks With
Time-Varying Delays.
AB - This paper is concerned with the finite-time synchronization problem of coupled
hierarchical hybrid delayed neural networks. This coupled hierarchical hybrid
neural networks consist of a higher level switching and a lower level Markovian
jumping. The time-varying delays are dependent on not only switching signal but
also jumping mode. By using a less conservative weighted integral inequality and
stochastic multiple Lyapunov-Krasovskii functional, new finite-time
synchronization criteria are obtained, which makes the state trajectories be kept
within the prescribed bound in a time interval. Finally, an example is proposed
to demonstrate the effectiveness of the obtained results.
PMID- 28422676
TI - Supervised and Unsupervised Aspect Category Detection for Sentiment Analysis with
Co-occurrence Data.
AB - Using online consumer reviews as electronic word of mouth to assist purchase
decision making has become increasingly popular. The Web provides an extensive
source of consumer reviews, but one can hardly read all reviews to obtain a fair
evaluation of a product or service. A text processing framework that can
summarize reviews, would therefore be desirable. A subtask to be performed by
such a framework would be to find the general aspect categories addressed in
review sentences, for which this paper presents two methods. In contrast to most
existing approaches, the first method presented is an unsupervised method that
applies association rule mining on co-occurrence frequency data obtained from a
corpus to find these aspect categories. While not on par with state-of-the-art
supervised methods, the proposed unsupervised method performs better than several
simple baselines, a similar but supervised method, and a supervised baseline,
with an -score of 67%. The second method is a supervised variant that outperforms
existing methods with an -score of 84%.
PMID- 28422677
TI - Learning Sparse Representation for Objective Image Retargeting Quality
Assessment.
AB - The goal of image retargeting is to adapt source images to target displays with
different sizes and aspect ratios. Different retargeting operators create
different retargeted images, and a key problem is to evaluate the performance of
each retargeting operator. Subjective evaluation is most reliable, but it is
cumbersome and labor-consuming, and more importantly, it is hard to be embedded
into online optimization systems. This paper focuses on exploring the
effectiveness of sparse representation for objective image retargeting quality
assessment. The principle idea is to extract distortion sensitive features from
one image (e.g., retargeted image) and further investigate how many of these
features are preserved or changed in another one (e.g., source image) to measure
the perceptual similarity between them. To create a compact and robust feature
representation, we learn two overcomplete dictionaries to represent the
distortion sensitive features of an image. Features including local geometric
structure and global context information are both addressed in the proposed
framework. The intrinsic discriminative power of sparse representation is then
exploited to measure the similarity between the source and retargeted images.
Finally, individual quality scores are fused into an overall quality by a typical
regression method. Experimental results on several databases have demonstrated
the superiority of the proposed method.
PMID- 28422678
TI - Correlation Filter Learning Toward Peak Strength for Visual Tracking.
AB - This paper presents a novel visual tracking approach to correlation filter
learning toward peak strength of correlation response. Previous methods leverage
all features of the target and the immediate background to learn a correlation
filter. Some features, however, may be distractive to tracking, like those from
occlusion and local deformation, resulting in unstable tracking performance. This
paper aims at solving this issue and proposes a novel algorithm to learn the
correlation filter. The proposed approach, by imposing an elastic net constraint
on the filter, can adaptively eliminate those distractive features in the
correlation filtering. A new peak strength metric is proposed to measure the
discriminative capability of the learned correlation filter. It is demonstrated
that the proposed approach effectively strengthens the peak of the correlation
response, leading to more discriminative performance than previous methods.
Extensive experiments on a challenging visual tracking benchmark demonstrate that
the proposed tracker outperforms most state-of-the-art methods.
PMID- 28422679
TI - A Bio-Inspired Approach to Traffic Network Equilibrium Assignment Problem.
AB - Finding an equilibrium state of the traffic assignment plays a significant role
in the design of transportation networks. We adapt the path finding mathematical
model of slime mold Physarum polycephalum to solve the traffic equilibrium
assignment problem. We make three contributions in this paper. First, we propose
a generalized Physarum model to solve the shortest path problem in directed and
asymmetric graphs. Second, we extend it further to resolve the network design
problem with multiple source nodes and sink nodes. At last, we demonstrate that
the Physarum solver converges to the user-optimized (Wardrop) equilibrium by
dynamically updating the costs of links in the network. In addition, convergence
of the developed algorithm is proved. Numerical examples are used to demonstrate
the efficiency of the proposed algorithm. The superiority of the proposed
algorithm is demonstrated in comparison with several other algorithms, including
the Frank-Wolfe algorithm, conjugate Frank-Wolfe algorithm, biconjugate Frank
Wolfe algorithm, and gradient projection algorithm.
PMID- 28422680
TI - A Unified Framework for Tracking Based Text Detection and Recognition from Web
Videos.
AB - Video text extraction plays an important role for multimedia understanding and
retrieval. Most previous research efforts are conducted within individual frames.
A few of recent methods, which pay attention to text tracking using multiple
frames, however, do not effectively mine the relations among text detection,
tracking and recognition. In this paper, we propose a generic Bayesian-based
framework of Tracking based Text Detection And Recognition (T DAR) from web
videos for embedded captions, which is composed of three major components, i.e.,
text tracking, tracking based text detection, and tracking based text
recognition. In this unified framework, text tracking is first conducted by
tracking-by-detection. Tracking trajectories are then revised and refined with
detection or recognition results. Text detection or recognition is finally
improved with multi-frame integration. Moreover, a challenging video text
(embedded caption text) database (USTB-VidTEXT) is constructed and publicly
available. A variety of experiments on this dataset verify that our proposed
approach largely improves the performance of text detection and recognition from
web videos.
PMID- 28422681
TI - Fast Median Filtering for Phase or Orientation Data.
AB - Median filtering is among the most utilized tools for smoothing real-valued data,
as it is robust, edge-preserving, value-preserving, and yet can be computed
efficiently. For data living on the unit circle, such as phase data or
orientation data, a filter with similar properties is desirable. For these data,
there is no unique means to define a median; so we discuss various possibilities.
The arc distance median turns out to be the only variant which leads to robust,
edge-preserving and value-preserving smoothing. However, there are no efficient
algorithms for filtering based on the arc distance median. Here, we propose fast
algorithms for filtering of signals and images with values on the unit circle
based on the arc distance median. For non-quantized data, we develop an algorithm
that scales linearly with the filter size. The runtime of our reference
implementation is only moderately higher than the Matlab implementation of the
classical median filter for real-valued data. For quantized data, we obtain an
algorithm of constant complexity w.r.t. the filter size. We demonstrate the
performance of our algorithms for real life data sets: phase images from
interferometric synthetic aperture radar, planar flow fields from optical flow,
and time series of wind directions.
PMID- 28422682
TI - MRI-Based Medial Axis Extraction and Boundary Segmentation of Cranial Nerves
Through Discrete Deformable 3D Contour and Surface Models.
AB - This paper presents a segmentation technique to identify the medial axis and the
boundary of cranial nerves. We utilize a 3-D deformable one-simplex discrete
contour model to extract the medial axis of each cranial nerve. This contour
model represents a collection of two-connected vertices linked by edges, where
vertex position is determined by a Newtonian expression for vertex kinematics
featuring internal and external forces, the latter of which include attractive
forces toward the nerve medial axis. We exploit multiscale vesselness filtering
and minimal path techniques in the medial axis extraction method, which also
computes a radius estimate along the path. Once we have the medial axis and the
radius function of a nerve, we identify the nerve surface using a two-simplex
deformable model, which expands radially and can accommodate any nerve shape. As
a result, the method proposed here combines the benefits of explicit contour and
surface models, while also achieving a cornerstone for future work that will
emphasize shape statistics, static collision with other critical structures, and
tree-shape analysis.
PMID- 28422684
TI - Visual Analysis of Inclusion Dynamics in Two-Phase Flow.
AB - In single-phase flow visualization, research focuses on the analysis of vector
field properties. In two-phase flow, in contrast, analysis of the phase
components is typically of major interest. So far, visualization research of two
phase flow concentrated on proper interface reconstruction and the analysis
thereof. In this paper, we present a novel visualization technique that enables
the investigation of complex two-phase flow phenomena with respect to the physics
of breakup and coalescence of inclusions. On the one hand, we adapt dimensionless
quantities for a localized analysis of phase instability and breakup, and provide
detailed inspection of breakup dynamics with emphasis on oscillation and its
interplay with rotational motion. On the other hand, we present a parametric
tightly linked space-time visualization approach for an effective interactive
representation of the overall dynamics. We demonstrate the utility of our
approach using several two-phase CFD datasets.
PMID- 28422683
TI - Progressive Dictionary Learning With Hierarchical Predictive Structure for Low
Bit-Rate Scalable Video Coding.
AB - Dictionary learning has emerged as a promising alternative to the conventional
hybrid coding framework. However, the rigid structure of sequential training and
prediction degrades its performance in scalable video coding. This paper proposes
a progressive dictionary learning framework with hierarchical predictive
structure for scalable video coding, especially in low bitrate region. For
pyramidal layers, sparse representation based on spatio-temporal dictionary is
adopted to improve the coding efficiency of enhancement layers with a guarantee
of reconstruction performance. The overcomplete dictionary is trained to
adaptively capture local structures along motion trajectories as well as exploit
the correlations between the neighboring layers of resolutions. Furthermore,
progressive dictionary learning is developed to enable the scalability in
temporal domain and restrict the error propagation in a closed-loop predictor.
Under the hierarchical predictive structure, online learning is leveraged to
guarantee the training and prediction performance with an improved convergence
rate. To accommodate with the state-of-the-art scalable extension of H.264/AVC
and latest High Efficiency Video Coding (HEVC), standardized codec cores are
utilized to encode the base and enhancement layers. Experimental results show
that the proposed method outperforms the latest scalable extension of HEVC and
HEVC simulcast over extensive test sequences with various resolutions.
PMID- 28422685
TI - Outdoor Markerless Motion Capture with Sparse Handheld Video Cameras.
AB - We present a method for outdoor markerless motion capture with sparse handheld
video cameras. In the simplest setting, it only involves two mobile phone cameras
following the character. This setup can maximize the flexibilities of data
capture and broaden the applications of motion capture. To solve the character
pose under such challenge settings, we exploit the generative motion capture
methods and propose a novel model-view consistency that considers both foreground
and background in the tracking stage. The background is modeled as a deformable
2D grid, which allows us to compute the background-view consistency for sparse
moving cameras. The 3D character pose is tracked with a global-local optimization
through minimizing our consistency cost. A novel motion regularizer is also
proposed in the optimization to constrain the solution pose space. The whole
process of the proposed method is simple as frame by frame video segmentation is
not required. Our method outperforms several alternative methods on various
examples demonstrated in the paper.
PMID- 28422686
TI - An Integrated Movement Analysis Framework to Study Upper Limb Function: A Pilot
Study.
AB - The functional capabilities of individuals with upper limb disabilities are
assessed throughout rehabilitation and treatment regimens using functional
outcome measures. For the upper limb amputee population, there are none which
quantitatively take into account the quality of movement while an individual is
performing tasks. In this paper, we demonstrate the use of an integrated movement
analysis framework, based on motion capture and ground reaction force data, to
capture quantitative information about how subjects complete a commonly used
functional outcome measure, the Box and Blocks Test (BBT). In order to test the
usefulness of the integrated movement analysis framework in capturing the quality
of movements during task performance, a motion restriction was induced in able
bodied participants that reproduces some of the limitations imposed by
conventional prosthetics. Each subject performed the BBT under normal conditions
and also under the motion restriction condition. The motion capture and ground
force plates captured movement that significantly differed between the two
conditions, with the largest differences seen in shoulder motion, in the range of
motions of head tilt and elbow flexion, and in the area of the center of pressure
trajectory. These preliminary results show the feasibility of incorporating
standardized, quantitative movement analysis into the assessment of function for
those with an upper limb disability.
PMID- 28422688
TI - Person Reidentification Based on Elastic Projections.
AB - Person reidentification usually refers to matching people in different camera
views in nonoverlapping multicamera networks. Many existing methods learn a
similarity measure by projecting the raw feature to a latent subspace to make the
same target's distance smaller than different targets' distances. However, the
same targets captured in different camera views should hold the same intrinsic
attributes while different targets should hold different intrinsic attributes.
Projecting all the data to the same subspace would cause loss of such an
information and comparably poor discriminability. To address this problem, in
this paper, a method based on elastic projections is proposed to learn a pairwise
similarity measure for person reidentification. The proposed model learns two
projections, positive projection and negative projection, which are both
representative and discriminative. The representability refers to: for the same
targets captured in two camera views, the positive projection can bridge the
corresponding appearance variation and represent the intrinsic attributes of the
same targets, while for the different targets captured in two camera views, the
negative projection can explore and utilize the different attributes of different
targets. The discriminability means that the intraclass distance should become
smaller than its original distance after projection, while the interclass
distance becomes larger on the contrary, which is the elastic property of the
proposed model. In this case, prior information of the original data space is
used to give guidance for the learning phase; more importantly, similar targets
(but not the same) are effectively reduced by forcing the same targets to become
more similar and different targets to become more distinct. The proposed model is
evaluated on three benchmark data sets, including VIPeR, GRID, and CUHK, and
achieves better performance than other methods.
PMID- 28422687
TI - Theoretical Limits on Multiuser Molecular Communication in Internet of Nano-Bio
Things.
AB - In nano-bio networks, multiple transmitter-receiver pairs will operate in the
same medium. Both inter-symbol interference and multi-user interference can cause
saturation at the receiver side, and this effect may cause an outage. Thus, we
propose a tractable framework to calculate the theoretical operating points for
fully absorbing receiver.
PMID- 28422689
TI - A Novel Recurrent Neural Network for Manipulator Control With Improved Noise
Tolerance.
AB - In this paper, we propose a novel recurrent neural network to resolve the
redundancy of manipulators for efficient kinematic control in the presence of
noises in a polynomial type. Leveraging the high-order derivative properties of
polynomial noises, a deliberately devised neural network is proposed to eliminate
the impact of noises and recover the accurate tracking of desired trajectories in
workspace. Rigorous analysis shows that the proposed neural law stabilizes the
system dynamics and the position tracking error converges to zero in the presence
of noises. Extensive simulations verify the theoretical results. Numerical
comparisons show that existing dual neural solutions lose stability when exposed
to large constant noises or time-varying noises. In contrast, the proposed
approach works well and has a low tracking error comparable to noise-free
situations.
PMID- 28422690
TI - Doubly Nonparametric Sparse Nonnegative Matrix Factorization Based on Dependent
Indian Buffet Processes.
AB - Sparse nonnegative matrix factorization (SNMF) aims to factorize a data matrix
into two optimized nonnegative sparse factor matrices, which could benefit many
tasks, such as document-word co-clustering. However, the traditional SNMF
typically assumes the number of latent factors (i.e., dimensionality of the
factor matrices) to be fixed. This assumption makes it inflexible in practice. In
this paper, we propose a doubly sparse nonparametric NMF framework to mitigate
this issue by using dependent Indian buffet processes (dIBP). We apply a
correlation function for the generation of two stick weights associated with each
column pair of factor matrices while still maintaining their respective marginal
distribution specified by IBP. As a consequence, the generation of two factor
matrices will be columnwise correlated. Under this framework, two classes of
correlation function are proposed: 1) using bivariate Beta distribution and 2)
using Copula function. Compared with the single IBP-based NMF, this paper jointly
makes two factor matrices nonparametric and sparse, which could be applied to
broader scenarios, such as co-clustering. This paper is seen to be much more
flexible than Gaussian process-based and hierarchial Beta process-based dIBPs in
terms of allowing the two corresponding binary matrix columns to have greater
variations in their nonzero entries. Our experiments on synthetic data show the
merits of this paper compared with the state-of-the-art models in respect of
factorization efficiency, sparsity, and flexibility. Experiments on real-world
data sets demonstrate the efficiency of this paper in document-word co-clustering
tasks.
PMID- 28422691
TI - Event-Sampled Direct Adaptive NN Output- and State-Feedback Control of Uncertain
Strict-Feedback System.
AB - In this paper, a novel event-triggered implementation of a tracking controller
for an uncertain strict-feedback system is presented. Neural networks (NNs) are
utilized in the backstepping approach to design a control input by approximating
unknown dynamics of the strict-feedback nonlinear system with event-sampled
inputs. The system state vector is assumed to be unknown and an NN observer is
used to estimate the state vector. By using the estimated state vector and
backstepping design approach, an event-sampled controller is introduced. As part
of the controller design, first, input-to-state-like stability for a continuously
sampled controller that has been injected with bounded measurement errors is
demonstrated, and subsequently, an event-execution control law is derived, such
that the measurement errors are guaranteed to remain bounded. Lyapunov theory is
used to demonstrate that the tracking errors, the observer estimation errors, and
the NN weight estimation errors for each NN are locally uniformly ultimately
bounded in the presence bounded disturbances, NN reconstruction errors, as well
as errors introduced by event sampling. Simulation results are provided to
illustrate the effectiveness of the proposed controllers.
PMID- 28422692
TI - Safe Screening Rules for Accelerating Twin Support Vector Machine Classification.
AB - The twin support vector machine (TSVM) is widely used in classification problems,
but it is not efficient enough for large-scale data sets. Furthermore, to get the
optimal parameter, the exhaustive grid search method is applied to TSVM. It is
very time-consuming, especially for multiparameter models. Although many
techniques have been presented to solve these problems, all of them always affect
the performance of TSVM to some extent. In this paper, we propose a safe
screening rule (SSR) for linear-TSVM, and give a modified SSR (MSSR) for
nonlinear TSVM, which contains multiple parameters. The SSR and MSSR can delete
most training samples and reduce the scale of TSVM before solving it. Sequential
versions of SSR and MSSR are further introduced to substantially accelerate the
whole parameter tuning process. One important advantage of SSR and MSSR is that
they are safe, i.e., we can obtain the same solution as the original problem by
utilizing them. Experiments on eight real-world data sets and an imbalanced data
set with different imbalanced ratios demonstrate the efficiency and safety of SSR
and MSSR.
PMID- 28422693
TI - Singularities of Three-Layered Complex-Valued Neural Networks With Split
Activation Function.
AB - There are three important concepts related to learning processes in neural
networks: reducibility, nonminimality, and singularity. Although the definitions
of these three concepts differ, they are equivalent in real-valued neural
networks. This is also true of complex-valued neural networks (CVNNs) with hidden
neurons not employing biases. The situation of CVNNs with hidden neurons
employing biases, however, is very complicated. Exceptional reducibility was
found, and it was shown that reducibility and nonminimality are not the same.
Irreducibility consists of minimality and exceptional reducibility. The
relationship between minimality and singularity has not yet been established. In
this paper, we describe our surprising finding that minimality and singularity
are independent. We also provide several examples based on exceptional
reducibility.
PMID- 28422694
TI - Synchronization Criteria for Discontinuous Neural Networks With Mixed Delays via
Functional Differential Inclusions.
AB - This paper investigates the issue of global exponential synchronization for a
class of general neural networks that contains discontinuous activation functions
and mixed time delays. Functional differential inclusions and nonsmooth analysis
theories are used as bases to design discontinuous controllers, such that the
discontinuous neural networks can be exponential complete synchronized. This
novel approach and its applicability to neural networks with continuous
activations are also easily verified. Several numerical examples demonstrate the
practicality and effectiveness of the design method.
PMID- 28422695
TI - On the Impact of Regularization Variation on Localized Multiple Kernel Learning.
AB - This brief analyzes the effects of regularization variations in the localized
kernel weights on the hypothesis generated by localized multiple kernel learning
(LMKL) algorithms. Recent research on LMKL includes imposing different
regularizations on the localized kernel weights and has led to varying
formulations and solution strategies. Following the stability analysis theory as
presented by Bousquet and Elisseeff, we give stability bounds based on the norm
of the variation of localized kernel weights for three LMKL methods cast in the
support vector machine classification framework, including vector -norm LMKL,
matrix-regularized -norm LMKL, and samplewise -norm LMKL. Further comparison of
these bounds helps to qualitatively reveal the performance differences produced
by these regularization methods, that is, matrix-regularized LMKL achieves
superior performance, followed by vector -norm LMKL and samplewise -norm LMKL.
Finally, a set of experimental results on ten benchmark machine learning UCI data
sets is reported and shown to empirically support our theoretical analysis.
PMID- 28422696
TI - New Conditions for Global Asymptotic Stability of Memristor Neural Networks.
AB - Recent papers in the literature introduced a class of neural networks (NNs) with
memristors, named dynamic-memristor (DM) NNs, such that the analog processing
takes place in the charge-flux domain, instead of the typical current-voltage
domain as it happens for Hopfield NNs and standard cellular NNs. One key
advantage is that, when a steady state is reached, all currents, voltages, and
power of a DM-NN drop off, whereas the memristors act as nonvolatile memories
that store the processing result. Previous work in the literature addressed
multistability of DM-NNs, i.e., convergence of solutions in the presence of
multiple asymptotically stable equilibrium points (EPs). The goal of this paper
is to study a basically different dynamical property of DM-NNs, namely, to
thoroughly investigate the fundamental issue of global asymptotic stability (GAS)
of the unique EP of a DM-NN in the general case of nonsymmetric neuron
interconnections. A basic result on GAS of DM-NNs is established using Lyapunov
method and the concept of Lyapunov diagonally stable matrices. On this basis,
some relevant classes of nonsymmetric DM-NNs enjoying the property of GAS are
highlighted.
PMID- 28422697
TI - Manifold Regularized Correlation Object Tracking.
AB - In this paper, we propose a manifold regularized correlation tracking method with
augmented samples. To make better use of the unlabeled data and the manifold
structure of the sample space, a manifold regularization-based correlation filter
is introduced, which aims to assign similar labels to neighbor samples.
Meanwhile, the regression model is learned by exploiting the block-circulant
structure of matrices resulting from the augmented translated samples over
multiple base samples cropped from both target and nontarget regions. Thus, the
final classifier in our method is trained with positive, negative, and unlabeled
base samples, which is a semisupervised learning framework. A block optimization
strategy is further introduced to learn a manifold regularization-based
correlation filter for efficient online tracking. Experiments on two public
tracking data sets demonstrate the superior performance of our tracker compared
with the state-of-the-art tracking approaches.
PMID- 28422698
TI - Dissipativity-Based Resilient Filtering of Periodic Markovian Jump Neural
Networks With Quantized Measurements.
AB - The problem of dissipativity-based resilient filtering for discrete-time periodic
Markov jump neural networks in the presence of quantized measurements is
investigated in this paper. Due to the limited capacities of network medium, a
logarithmic quantizer is applied to the underlying systems. Considering the fact
that the filter is realized through a network, randomly occurring parameter
uncertainties of the filter are modeled by two mode-dependent Bernoulli
processes. By establishing the mode-dependent periodic Lyapunov function,
sufficient conditions are given to ensure the stability and dissipativity of the
filtering error system. The filter parameters are derived via solving a set of
linear matrix inequalities. The merits and validity of the proposed design
techniques are verified by a simulation example.
PMID- 28422699
TI - Hemorrhage Prediction Models in Surgical Intensive Care: Bedside Monitoring Data
Adds Information to Lab Values.
AB - Hemorrhage is a frequent complication in surgery patients; its identification and
management have received increasing attention as a target for quality improvement
in patient care in the Intensive Care Unit (ICU). The purposes of this work were
1) to find an early detection model for hemorrhage by exploring the range of data
mining methods that are currently available, and 2) to compare prediction models
utilizing continuously measured physiological data from bedside monitors to those
using commonly obtained laboratory tests. We studied 3766 patients admitted to
the University of Virginia Health System Surgical Trauma Burn ICU. Hemorrhage was
defined as three or more units of red blood cells transfused within 24 h without
red blood cell transfusion in the preceding 24 h. 222 patients (5.9%) experienced
a hemorrhage, and multivariate models based on vital signs and their trends
showed good results (AUC = 76.1%). The hematocrit, not surprisingly, had
excellent performance (AUC = 87.7%). Models that included both continuous
monitoring and laboratory tests had the best performance (AUC = 92.2%). The
results point to a combined strategy of continuous monitoring and intermittent
lab tests as a reasonable clinical approach to the early detection of hemorrhage
in the surgical ICU.
PMID- 28422700
TI - Adaptive Fuzzy Control for Nonstrict Feedback Systems With Unmodeled Dynamics and
Fuzzy Dead Zone via Output Feedback.
AB - This paper investigates the problem of observer-based adaptive fuzzy control for
a category of nonstrict feedback systems subject to both unmodeled dynamics and
fuzzy dead zone. Through constructing a fuzzy state observer and introducing a
center of gravity method, unmeasurable states are estimated and the fuzzy dead
zone is defuzzified, respectively. By employing fuzzy logic systems to identify
the unknown functions. And combining small-gain approach with adaptive
backstepping control technique, a novel adaptive fuzzy output feedback control
strategy is developed, which ensures that all signals involved are semi-globally
uniformly bounded. Simulation results are given to demonstrate the effectiveness
of the presented method.
PMID- 28422701
TI - Aperiodic Optimal Linear Estimation for Networked Systems With Communication
Uncertainties.
AB - The aperiodic optimal linear estimator design problem is investigated in this
paper for networked systems with communication uncertainties, including delays
and data losses, where the sampling and estimation are nonuniform and
asynchronous. Based on the idea of measurement fusion, two approaches are
proposed to design the aperiodic estimators, and it is shown that the estimator
is equivalent to that designed by the measurement augmentation method in
performance. Moreover, the estimation performance is improved by using a newly
proposed measurement retransmission scheme as compared with the commonly used
hold-input and zero-input schemes, by which the lost measurements are never used
once they are lost.
PMID- 28422702
TI - Neuronal State Estimation for Neural Networks With Two Additive Time-Varying
Delay Components.
AB - This paper is concerned with the state estimation for neural networks with two
additive time-varying delay components. Three cases of these two time-varying
delays are fully considered: 1) both delays are differentiable uniformly bounded
with delay-derivative bounded by some constants; 2) one delay is continuous
uniformly bounded while the other is differentiable uniformly bounded with delay
derivative bounded by certain constants; and 3) both delays are continuous
uniformly bounded. First, an extended reciprocally convex inequality is
introduced to bound reciprocally convex combinations appearing in the derivative
of some Lyapunov-Krasovskii functional. Second, sufficient conditions are derived
based on the extended inequality for three cases of time-varying delays,
respectively. Third, a linear-matrix-inequality-based approach with two tuning
parameters is proposed to design desired Luenberger estimators such that the
error system is globally asymptotically stable. This approach is then applied to
state estimation on neural networks with a single interval time-varying delay.
Finally, two numerical examples are given to illustrate the effectiveness of the
proposed method.
PMID- 28422703
TI - Differential hemoglobin A sequestration between hemodialysis modalities.
AB - This report evaluates plasma protein patterns, dialysates and protein analysis of
used dialysis membranes from the same patient under hemodialysis in three
separate modalities, using high-flux membranes in concentration-driven transport
(HD), convection-driven hemofiltration (HF) and combined hemodialfiltration
(HDF). The plasma protein changes induced by each of the three dialysis
modalities showed small differences in proteins identified towards our previous
plasma analyses of chronic kidney disease (CKD) patients. The used dialysate
peptide concentrations likewise exhibited small differences among the modalities
and varied in the same relative order as the plasma changes, with protein losses
in the order HD>HDF>HF. The membrane protein deposits allowed quantification of
the relative Hb removal ratios as ~1.7 for HD and ~1.2 for HDF vs. ~1.0 for HF.
Hence, plasma protein alterations, dialysate peptide contents and membrane Hb
deposits all identify HD as the modality with the most extensive filtration
results and exemplifies the accessibility of protein analysis of used membrane
filters for evaluation of dialysis efficiencies.
PMID- 28422704
TI - Influencing factors on high-risk sexual behaviors in young people: an ecological
perspective.
AB - Background In recent years, high-risk sexual behaviors due to their negative
consequences both for the individual and society have received more attention
than other high-risk behaviors. Objective The aim of this study was to review the
influencing factors of high-risk sexual behaviors among young people from an
ecological point of view. Methods This review was conducted through searching
databases including PubMed, Web of Science, Scopus, Google Scholar and the
Cochrane Library with keywords such as sexual risk-taking behavior, high-risk
sex, unprotected sex and unsafe sex. The relevant papers published between 1995
and 2016 were extracted. After reviewing the abstract and full text of the
articles, 45 papers were used to write this article. Results From an ecological
theory approach, factors which influence high-risk sexual behaviors are divided
into three categories - the microsystem, the mesosystem and the macrosystem. The
microsystem includes factors such as age, gender, race, marital status, place of
residence, religion, level of education, personality traits, psychological
problems, childhood experiences, body image and coincidence of high-risk
behaviors; the mesosystem includes factors such as family structure, peers and
sex education; in the macrosystem, the impact of culture and traditions of the
society, economic status and the media are presented. Conclusion Given that high
risk sexual behaviors often have multiple causes, it seems that health
policymakers must consider multi-dimensional interventions to influence high-risk
sexual behaviors based on the ecological approach.
PMID- 28422705
TI - Plasma kisspeptin and ghrelin levels in puberty variant cases.
AB - BACKGROUND: The aim of this study was to determine the serum levels of kisspeptin
and ghrelin (GAH), as well as the relationship of these two peptides with each
other in premature thelarche (PT) and premature adrenarche (PA) cases and to
investigate the possibility of using these peptides as markers in the
differentiation of puberty disorders. METHODS: A PT group aged 1-8 years (n =
40), a PA group aged 1-9 years (n = 23, female/male = 20/3) and control groups
consistent with each of the previous groups in terms of age and gender were
created for the study. Kisspeptin and ghrelin levels were measured with ELISA
methods from blood samples drawn while fasting in the morning. RESULTS: When the
PT group was compared with the controls, the plasma kisspeptin levels of the
cases were significantly higher than the control group (165.47 +/- 15.45 pmol/L,
96.82 +/- 12.33 pmol/L, p = 0.005, respectively). Kisspeptin levels in the PA
group did not show a difference with the control group (121.36 +/- 17.99 pmol/L,
95.52 +/- 11.54 pmol/L, p = 0.249, respectively). No significant difference could
be found when GAH levels in the PT and PA groups were compared with controls. No
significant correlation was found between kisspeptin and GAH levels in the PT and
PA groups. CONCLUSIONS: Our results indicate that kisspeptin plays an important
role in the PT, but GAH is not associated with puberty disorders.
PMID- 28422706
TI - Adult hippocampal neurogenesis: an important target associated with
antidepressant effects of exercise.
AB - Depression is a prevalent devastating mental disorder that affects the normal
life of patients and brings a heavy burden to whole society. Although many
efforts have been made to attenuate depressive/anxiety symptoms, the current
clinic antidepressants have limited effects. Scientists have long been making
attempts to find some new strategies that can be applied as the alternative
antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been
suggested as a therapy that can relieve psychiatric stress. However, how exercise
improves the brain functions and reaches the antidepressant target needs
systematic summarization due to the complexity and heterogeneous feature of
depression. Brain plasticity, especially adult neurogenesis in the hippocampus,
is an important neurophysiology to facilitate animals for neurogenesis can occur
in not only humans. Many studies indicated that an appropriate level of exercise
can promote neurogenesis in the adult brains. In this article, we provide
information about the antidepressant effects of exercise and its implications in
adult neurogenesis. From the neurogenesis perspective, we summarize evidence
about the effects of exercise in enhancing neurogenesis in the hippocampus
through regulating growth factors, neurotrophins, neurotransmitters and
metabolism as well as inflammations. Taken together, a large number of published
works indicate the multiple benefits of exercise in the brain functions of
animals, particularly brain plasticity like neurogenesis and synaptogenesis.
Therefore, a new treatment method for depression therapy can be developed by
regulating the exercise activity.
PMID- 28422707
TI - Factors underlying cognitive decline in old age and Alzheimer's disease: the role
of the hippocampus.
AB - There are many factors that strongly influence the aetiology, development, and
progression of cognitive decline in old age, mild cognitive impairment (MCI), and
Alzheimer's disease (AD). These factors include not only different personality
traits and moods but also lifestyle patterns (e.g. exercise and diet) and
awareness levels that lead to cognitive decline in old age. In this review, we
discuss how personality traits, mood states, and lifestyle impact brain and
behaviour in older adults. Specifically, our review shows that these lifestyle
and personality factors affect several brain regions, including the hippocampus,
a region key for memory that is affected by cognitive decline in old age as well
as AD. Accordingly, appropriate recommendations are presented in this review to
assist individuals in decreasing chances of MCI, dementia, AD, and associated
symptoms.
PMID- 28422708
TI - A brief essay on non-pharmacological treatment of Alzheimer's disease.
AB - Current pharmacological therapies for Alzheimer's disease (AD) do not modify its
course and are not always beneficial. Therefore, the optimization of quality of
life represents the best possible outcome achievable in all stages of the
disease. Cognitive and behavioural rehabilitation represents the main therapeutic
approach for this purpose, also in order to mitigate indirectly the burden of
distress of family caregivers. The aim of this mini-review is to go through this
theme by discussing cognitive activation, virtual reality and neuromodulation
techniques. The practices summarized in this essay are not alternative but,
often, complementary therapies to standardized pharmacological treatment. The
present mini-review has found encouraging results but also the need for more
conclusive evidence for all types of non-invasive/non-pharmacological treatment
of AD.
PMID- 28422709
TI - Preterm birth among women living within 600 meters of high voltage overhead Power
Lines: a case-control study.
AB - AIM: The issue of preterm birth due to exposure to magnetic fields from power
lines is unclear. Exposure to electromagnetic field in uterus has been
hypothesized as possible preterm birth. The aim of the present study was to
determine whether living closer to high voltage power lines increased the risk of
preterm labor. METHODS: In a nested case-control study, 135 cases of singleton
live spontaneous preterm birth in Rohani hospital, Babol, Iran, during the period
between 2013 and 2014 were studied. The 150 control subjects were singleton term
live birth in the same year of birth and city of residence using randomized-digit
dialing. The shortest distance to any of the high voltage power lines to the
maternal residence during pregnancy was measured using ArcGIS software for every
case and control. To test the association between the preterm births and the
residential proximity to power lines, stepwise multiple logistic regression was
used. RESULTS: There were 28 households, 20 cases (14.8%) and 8 controls (5.3%)
situated within 600 meters of high voltage power lines. The adjusted OR for
spontaneous preterm birth and birth defect in women who were living in less than
600 meters from high voltage power lines was higher compared to those living at
farther distance (OR = 3.28, CI: 1.37 to 7.85) and (OR = 5.05, CI: 1.52 to
16.78), respectively. CONCLUSIONS: Therefore, installing overhead power lines and
stations within 600 meters or making overhead underground would be useful in the
prevention of both preterm birth and birth defect.
PMID- 28422710
TI - The role of metabolic tumor volume (MTV) measured by [18F] FDG PET/CT in
predicting EGFR gene mutation status in non-small cell lung cancer.
AB - Many noninvasive methods have been explored to determine the mutation status of
the epidermal growth factor receptor (EGFR) gene, which is important for
individualized treatment of non-small cell lung cancer (NSCLC). We evaluated
whether metabolic tumor volume (MTV), a parameter measured by [18F]
fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT)
might help predict EGFR mutation status in NSCLC. Overall, 87 patients who
underwent EGFR genotyping and pretreatment PET/CT between January 2013 and
September 2016 were reviewed. Clinicopathologic characteristics and metabolic
parameters including MTV were evaluated. Univariate and multivariate analyses
were used to assess the independent variables that predict mutation status to
create prediction models. Forty-one patients (41/87) were identified as having
EGFR mutations. The multivariate analysis showed that patients with lower MTV
(MTV<=11.0 cm3, p=0.001) who were non-smokers (p=0.037) and had a peripheral
tumor location (p=0.033) were more likely to have EGFR mutations. Prediction
models using these criteria for EGFR mutation yielded a high AUC (0.805, 95% CI
0.712-0.899), which suggests that the analysis had good discrimination. In
conclusion, NSCLC patients with EGFR mutations showed significantly lower MTV
than patients with wild-type EGFR. Prediction models based on MTV and
clinicopathologic characteristics could provide more information for the
identification of EGFR mutations.
PMID- 28422711
TI - Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived
tumor xenograft models.
AB - Aberrant activation of histone lysine-specific demethylase (LSD1) increases
tumorigenicity; hence, LSD1 is considered a therapeutic target for various human
cancers. Although melatonin, an endogenously produced molecule, may defend
against various cancers, the precise mechanism involved in its anti-oral cancer
effect remains unclear. Patient-derived tumor xenograft (PDTX) models are
preclinical models that can more accurately reflect human tumor biology compared
with cell line xenograft models. Here, we evaluated the anticancer activity of
melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral
squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we
examined whether aberrant LSD1 overexpression in OSCC is associated with poor
prognosis. We also evaluated the action mechanism of melatonin against OSCC with
lymphatic metastases by using the PDTX models. Our results indicated that
melatonin, at pharmacological concentrations, significantly suppresses cell
proliferation in a dose- and time-dependent manner. The observed suppression of
proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in
oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that
the beneficial effects of melatonin in reducing oral cancer cell proliferation
are associated with reduced LSD1 expression in vivo and in vitro.
PMID- 28422712
TI - Combination analysis of NOS3, ABCB1 and IL23R polymorphisms with alcohol-induced
osteonecrosis of the femoral head risk in Chinese males.
AB - BACKGROUND: Common variants of multiple genes played a crucial role in
osteonecrosis of the femoral head (ONFH) onset which was proved by many previous
reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related
to individual differences in alcohol sensitivity and the development of alcohol
induced ONFH. METHODS: In this case-control study, we evaluated 8 SNPs in three
genes in the Chinese Han population including 355 male cases and 355 healthy male
controls. These SNPs were genotyped by Sequenom MassARRAY RS1000. To identify
their relationship with alcohol-induced ONFH susceptibility using chi2 test and
genetic model analysis. RESULTS: We found an association with alcohol-induced
ONFH susceptibility for 4 SNPs (rs743506, rs3918184, rs13233308 and rs6693831) in
three genes after adjusted by age. The genotype "G/A" of rs743506 in NOS3 gene
acts as a risk factor in genotype (P = 0.003), dominant (P = 0.048), recessive (P
= 0.005) and additive model(P = 0.006); The genotype "T/C" of rs3918184 in NOS3
gene acts as a risk factor in genotype (P = 0.012) and recessive model (P =
0.009); The genotype "T/C" of rs13233308 in ABCB1 gene acts as a risk factor in
genotype (P = 0.038) and additive model(P = 0.041); The genotype "T/C" of
rs6693831 in IL23R gene acts as a protective factor in genotype model (P =
0.046). CONCLUSIONS: This study provides evidence for three alcohol-induced ONFH
susceptibility genes (NOS3, ABCB1 and IL23R) in Chinese males and polymorphisms
of them may be associated with alcohol-induced ONFH risk.
PMID- 28422713
TI - SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of
serine phosphorylation of STAT1 and STAT5 transactivation domains.
AB - Inhibition of oncogenic transcriptional programs is a promising therapeutic
strategy. A substituted tricyclic benzimidazole, SEL120-34A, is a novel inhibitor
of Cyclin-dependent kinase 8 (CDK8), which regulates transcription by associating
with the Mediator complex. X-ray crystallography has shown SEL120-34A to be a
type I inhibitor forming halogen bonds with the protein's hinge region and
hydrophobic complementarities within its front pocket. SEL120-34A inhibits
phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells in vitro.
Consistently, regulation of STATs- and NUP98-HOXA9- dependent transcription has
been observed as a dominant mechanism of action in vivo. Treatment with the
compound resulted in a differential efficacy on AML cells with elevated STAT5
S726 levels and stem cell characteristics. In contrast, resistant cells were
negative for activated STAT5 and revealed lineage commitment. In vivo efficacy in
xenotransplanted AML models correlated with significant repression of STAT5 S726.
Favorable pharmacokinetics, confirmed safety and in vivo efficacy provide a
rationale for the further clinical development of SEL120-34A as a personalized
therapeutic approach in AML.
PMID- 28422714
TI - Toll like receptor 3 as an immunotherapeutic target for KRAS mutated colorectal
cancer.
AB - New therapeutic interventions are essential for improved management of patients
with metastatic colorectal cancer (mCRC). This is especially critical for those
patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all
patients). This patient cohort is excluded from receiving anti-EGFR monoclonal
antibodies that have added a significant therapeutic benefit for KRAS wild type
CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical
development for patients with chemotherapy refractory KRAS mutated tumors. Toll
Like Receptor (TLR) 3, a member of the toll like receptor family of the host
innate immune system is the pattern recognition motif for dsRNA pathogens. Using
TLR3 expressing commercial HEK-BlueTM-hTLR3 cells we confirm that TLR3 is the
host pattern recognition motif responsible for the detection of reovirus.
Further, our investigation with KRAS mutated HCT116 cell line showed that
effective expression of host TLR3 dampens the infection potential of reovirus by
mounting a robust innate immune response. Down regulation of TLR3 expression with
siRNA improves the anticancer activity of reovirus. In vivo experiments using
human CRC cells derived xenografts in athymic mice further demonstrate the
beneficial effects of TLR3 knock down by improving tumor response rates to
reovirus. Strategies to mitigate the TLR3 response pathway can be utilized as a
tool towards improved reovirus efficacy to specifically target the dissemination
of KRAS mutated CRC.
PMID- 28422715
TI - A novel BMX variant promotes tumor cell growth and migration in lung
adenocarcinoma.
AB - The non-receptor tyrosine kinase BMX has been reported in several solid tumors.
However, the alternative splicing of BMX and its clinical relevance in lung
cancer remain to be elucidated. Exon1.0 array was used to identify a novel
alternative splicing of BMX, BMXDeltaN, which was confirmed by rapid
amplification of cDNA ends and reverse transcription-polymerase chain reaction.
BMXDeltaN, resulting from exon skipping with excluding exon 1 to exon 8 of BMX
gene, was found in 12% human lung adenocarcinoma specimens. BMXDeltaN is not
found in paired pathologically normal lungs and positively correlated with EGFR
mutation in lung adenocarcinomas. Moreover, BMXDeltaN increases cell
proliferation, neoplastic transformation, and migratory property of human non
small cell lung cancer cells. The function of BMXDeltaN in lung cancer might be
presumably due to enhanced ERK signaling.
PMID- 28422716
TI - Sequential evaluation of CALR mutant burden in patients with myeloproliferative
neoplasms.
AB - We investigated the variation of CALR-mutant burden during follow-up in 105 CALR
mutant MPN and compared it to the variation of JAK2-mutant burden in 226 JAK2
mutant MPN.The median allele burden at last evaluation was significantly higher
than at first evaluation in essential thrombocythemia (ET) (49.5% vs 45%, P <
.001) but not in primary myelofibrosis (PMF) (52% vs 51%, P 0.398). Median values
of slope were positive both in ET (0.071) and in PMF (0.032). In CALR-mutant ET
there was a difference between natural and therapy-related slope (P 0.006).In the
JAK2-mutated cohort, the median allele burden at last evaluation was not
different respect to that at first evaluation, neither in ET (22.9% vs 23.2%, P =
0.216) nor in PMF (50.5% vs 45.0%, P = 0.809), despite a positive slope.
Multivariate analysis to evaluate the effect of mutation (CALR vs JAK2) on the
slope of mutant burden in not treated pts with a positive slope adjusting for
diagnosis (ET vs PMF) showed a trend toward a higher increase of mutant burden in
CALR vs JAK2 (beta = 0.19, P = 0.061) with no difference between diagnosis (P =
0.419). The findings of this study suggest that clonal expansion in CALR-mutant
MPN is faster than that observed in JAK2-mutant MPN.
PMID- 28422717
TI - C3orf21 ablation promotes the proliferation of lung adenocarcinoma, and its
mutation at the rs2131877 locus may serve as a susceptibility marker.
AB - In this study, we investigated the role of C3orf21 gene polymorphism at the
rs2131877 locus and its contribution to lung adenocarcinoma pathogenesis. Normal
lung and tumor tissue sections were collected from fifteen patients with lung
adenocarcinoma for chromosome 3 open reading frame 21 (C3orf21) genotype
analysis. In addition, a retrospective analysis was performed to assess the
association between C3orf21 genotype and tumor markers from patient samples used
in our previously published study. In parallel, we also manipulated C3orf21 gene
expression either by overexpressing or ablating it in a MSTO-211H human lung
cancer cell line to further understand its contribution to cell proliferation,
apoptosis and migration. Our results indicated that the patients with smoking
history had a significantly increased mutation (rs2131877 T/C+C/C genotype) rate
(p = 0.025), in addition to higher values for the CYF211 and NSE tumor markers (p
= 0.014 and p = 0.031, respectively). The retrospective analysis also confirmed
that the NSE marker value was higher in patients with a C3orf21 rs2131877 T/C+C/C
genotype. Furthermore, our in vitro data indicated that C3orf21 ablation promoted
lung cancer cell proliferation, inhibited apoptosis and accelerated cell
migration. Overall, our study concluded that C30rf21 rs 2131877 T/C+C/C genotype
patients may experience increased nicotine addiction and that C30rf21 can likely
serve as a susceptibility marker for lung adenocarcinoma with a higher degree of
malignancy.
PMID- 28422718
TI - Validation and optimization of the Ion Torrent S5 XL sequencer and Oncomine
workflow for BRCA1 and BRCA2 genetic testing.
AB - In this study, we validated the analytical performance of BRCA1/2 sequencing
using Ion Torrent's new bench-top sequencer with amplicon panel with optimized
bioinformatics pipelines. Using 43 samples that were previously validated by
Illumina's MiSeq platform and/or by Sanger sequencing/multiplex ligation
dependent probe amplification, we amplified the target with the OncomineTM BRCA
Research Assay and sequenced on Ion Torrent S5 XL (Thermo Fisher Scientific,
Waltham, MA, USA). We compared two bioinformatics pipelines for optimal
processing of S5 XL sequence data: the Torrent Suite with a plug-in Torrent
Variant Caller (Thermo Fisher Scientific), and commercial NextGENe software
(Softgenetics, State College, PA, USA). All expected 681 single nucleotide
variants, 15 small indels, and three copy number variants were correctly called,
except one common variant adjacent to a rare variant on the primer-binding site.
The sensitivity, specificity, false positive rate, and accuracy for detection of
single nucleotide variant and small indels of S5 XL sequencing were 99.85%, 100%,
0%, and 99.99% for the Torrent Variant Caller and 99.85%, 99.99%, 0.14%, and
99.99% for NextGENe, respectively. The reproducibility of variant calling was
100%, and the precision of variant frequency also showed good performance with
coefficients of variation between 0.32 and 5.29%. We obtained highly accurate
data through uniform and sufficient coverage depth over all target regions and
through optimization of the bioinformatics pipeline. We confirmed that our
platform is accurate and practical for diagnostic BRCA1/2 testing in a clinical
laboratory.
PMID- 28422719
TI - Fbxw7 haploinsufficiency loses its protection against DNA damage and accelerates
MNU-induced gastric carcinogenesis.
AB - Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein
substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor
suppressor via inducing apoptosis and growth arrest in various kinds of tumors.
To clarify the initiating role in gastric carcinogenesis as well as the
histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we
generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with
chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age. We also
treated mouse embryo fibroblasts (MEFs) from Fbxw7+/- and Fbxw7+/+ mice with MNU
and examined cell DNA damage via comet assay. The protein expression of Fbxw7 and
its substrate c-Myc from mouse tumors, as well as human tumors sampled from six
patients, were detected by Western blot. As results, the tumor incidence was
obviously higher in Fbxw7+/- mice (13/20) than in Fbxw7+/+ mice (6/20) after 35
week observation. Intestinal metaplasia (P = 0.013) and dysplasia (P = 0.036)
were more severe in Fbxw7+/- mice than in Fbxw7+/+ mice. The repair potential of
DNA damage was suppressed in MEFs from Fbxw7+/- mice after MNU exposure.
Increased c-Myc expression was accompanied by decreased Fbxw7 protein expression
in tumor tissues from mouse and patients. In conclusion, Fbxw7 haploinsufficiency
increased the risk of gastric carcinogenesis induced by MNU, which is associated
with the accumulation of DNA damage as well as c-Myc oncoprotein.
PMID- 28422720
TI - Overexpression of NOX4 predicts poor prognosis and promotes tumor progression in
human colorectal cancer.
AB - NADPH oxidase 4 (NOX4), a major source of reactive oxygen species (ROS)
production, has been increasingly reported to be involved in tumorigenesis and/or
tumor progression, but limited data are available regarding the role of NOX4 in
colorectal carcinoma (CRC). We retrieved six independent investigations from
Oncomine database and found that NOX4 is highly expressed in CRC tissues compared
with corresponding normal controls. Similar results were also found in clinical
specimens at both mRNA and protein levels. Immunohistochemical analysis indicated
that NOX4 overexpression was highly correlated with T classification, N
classification, distant metastasis, and poor prognosis of CRC patients, which was
also confirmed by GSE14333 and GSE17536 datasets from the Gene Expression
Omnibus. Furthermore, we demonstrated that when NOX4 expression was knocked down
by siRNAs, cell proliferation, cell-cycle and apoptosis, migration and invasion
were significantly altered in CRC cell lines HCT116 and LOVO. Meanwhile, NOX4
promoted cancer cell proliferation and apoptosis, migration and invasion by
regulating the expression of relevant genes. By these approaches we aim to
elucidate NOX4 may be a reliable prognostic factor or therapeutic target in CRC.
PMID- 28422721
TI - Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for
androgen-insensitive prostate cancer cell invasion.
AB - BACKGROUND: As one of the most common cancers in men, the pathogenesis of
prostate cancer has been widely researched. Aberrant activation of the erb-b2
receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in
metastatic prostate cancer. In our previous study, we demonstrated that
rs61552325 (Pro1140Ala) located in ERBB2 is strongly correlated to prostate
cancer. Therefore, we initially studied the effect of rs61552325 on androgen
independent prostate cancer cell metastasis. RESULTS: Bioinformatic results
demonstrated that the mutant Pro1140Ala likely decrease the stability of the
ERBB2 protein and its interactions. The mean migration rate after 6 h for PC3
minor variant cells which carried the G allele was 1.28-fold higher than major
variant PC3 cells that carried the C allele (P = 0.016). The mean invasion rate
of DU145 putative minor variant cells was 0.40 reducer than negative control
cells (P = 5.9E-04). METHODS: rs61552325 major variant (C allele) and minor
variant (G allele) were produced by site directed mutagenesis and transfected
into DU145 and PC3 cells. A wound healing assay was performed to compare
migration abilities between alleles. After knocking down endogenous ERBB2 and
then expressing the rs61552325 minor variant, invasion abilities were evaluated
with a transwell assay using DU145 and PC3 cells. CONCLUSIONS: Our data showed
that the rs61552325 major variant decreases PC3 cell migration and its minor
variant depresses DU145 cell invasion, suggesting that rs61552325 is likely an
important change during prostate cancer invasion.
PMID- 28422722
TI - The clinical value, regulatory mechanisms, and gene network of the cancer-testis
gene STK31 in pancreatic cancer.
AB - We aimed to identify STK31 as a cancer-testis (CT) gene and to explore its
potential clinical value, regulatory mechanisms, and gene network in pancreatic
cancer (PC). Gene expression data were generated from normal organ samples and
pancreatic cancer samples from three public databases. STK31 expression patterns
in normal and PC tissues were identified, and we explored its regulatory
mechanisms. Gene ontology (GO) and pathway analyses of STK31-related genes were
performed and an STK31 protein-protein interaction (PPI) network was constructed.
STK31 was confirmed as a CT gene in PC and its expression was significantly
higher in patients with new neoplasm compared with patients without new neoplasm
(P = 0.046) and in more advanced pathologic stages than in earlier stages (P =
0.002); methylation level correlated negatively with STK31 expression. In total,
757 STK31-related genes were identified, and were significantly enriched in terms
of polymorphisms and alternative splicings. The PPI network predicted that STK31
was physically associated with the PIWI (originally P-element Induced WImpy
testis in Drosophila) and Tudor families.
PMID- 28422723
TI - Serrated adenocarcinoma morphology in colorectal mucinous adenocarcinoma is
associated with improved patient survival.
AB - Colorectal mucinous adenocarcinoma (MAC) and serrated adenocarcinoma (SAC) share
many characteristics, including right-side colon location, frequent mucin
production, and various molecular features. This study examined the frequency of
SAC morphology in MACs. We assessed the correlation of SAC morphology with
clinicopathological parameters, molecular characteristics, and patient prognosis.
Eighty-eight colorectal MACs were collected and reviewed for SAC morphology
according to Makinen's criteria. We sequenced KRAS and BRAF, assessed CpG island
methylator phenotype (CIMP) frequency, and analyzed DNA mismatch repair enzyme
levels using immunohistochemistry in tumor samples. SAC morphology was observed
in 38% of MACs, and was associated with proximal location (P=0.001), BRAF
mutation (P=0.042), CIMP-positive status (P=0.023), and contiguous traditional
serrated adenoma (P=0.019). Multivariate analysis revealed that MACs without both
SAC morphology and CIMP-positive status exhibited 3.955 times greater risk of
cancer relapse than MACs having both characteristics or either one (P=0.035). Our
results show that two MAC groups with distinct features can be identified using
Makinen's criteria, and suggest a favorable prognostic role for the serrated
neoplastic pathway in colorectal MAC.
PMID- 28422724
TI - Utilizing combinatorial engineering to develop Tie2 targeting antagonistic
angiopoetin-2 ligands as candidates for anti-angiogenesis therapy.
AB - In many human cancers, the receptor tyrosine kinase (RTK) Tie2 plays important
roles in mediating proliferation, survival, migration and angiogenesis. Thus,
molecules that could potently inhibit activation of the Tie2 receptor would have
a significant impact on cancer therapy. Nevertheless, attempts to develop Tie2
targeted inhibitors have met with little success, and there is currently no FDA
approved therapeutic selectively targeting Tie2. We used a combinatorial protein
engineering approach to develop a new generation of angiopoietin (Ang)2-derived
Tie2 antagonists as potential cancer therapeutics and as tools to study
angiogenesis. The construct for designing a yeast surface display (YSD) library
of potential antagonists was an Ang2 binding domain (Ang2-BD) that retains Tie2
binding ability but prevents ligand multimerization and receptor dimerization and
activation. This mutant library was then screened by quantitative high-throughput
flow cytometric sorting to identify Ang2-BD variants with increased expression,
stability and affinity to Tie2. The selected variants were recombinantly
expressed and showed high affinity to soluble and cellular Tie2 and strongly
inhibited both Tie2 phosphorylation and endothelial capillary tube formation and
cell invasion compared to the parental Ang2-BD. The significance of the study
lies in the insight it provides into the sequence-structure-function
relationships and mechanism of action of the antagonistic Ang mutants. The
approach of using a natural protein ligand as a molecular scaffold for
engineering high-affinity agents can be applied to other ligands to create
functional protein antagonists against additional biomedical targets.
PMID- 28422725
TI - MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by
inhibiting mTOR signaling pathway and expression of MDR1.
AB - Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different
human malignancies, however, little is known about miR-199a-3p in
cholangiocarcinoma cells. In this study, we demonstrate the essential role and
mechanism of miR-199a-3p in regulating cisplatin sensitivity in
cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that
expression of miR-199a-3p was positively correlated with cisplatin sensitivity in
cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the
proliferation rate and increase apoptosis of cholangiocarcinoma cells in the
presence of cisplatin, while miR-199a-3p inhibition had the opposite effect.
Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that
miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced
the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue
experiments proved that miR-199a-3p could increase the cisplatin sensitivity of
cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also
found that miR-199a-3p overexpression could reduce cisplatin induced MDR1
expression by decreasing the synthesis and increasing the degradation of MDR1,
thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In
conclusion, miR-199a-3p could increase cisplatin sensitivity of
cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling
pathway and decreasing the expression of MDR1.
PMID- 28422726
TI - Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by
deregulating a c-src/FAK-associated signaling pathway.
AB - Recent studies have shown that increased syndecan-1 (SDC1) expression in human
glioma is associated with higher tumor grades and poor prognoses, but its
oncogenic functions and the underlying molecular mechanisms remain unknown. Here,
we examined SDC1 expression in datasets from The Cancer Genome Atlas and the
National Center for Biotechnology Information Gene Expression Omnibus. Elevated
SDC1 expression in glioma was closely associated with increases in tumor
progression and shorter survival. We also examined SDC1 expression and evaluated
the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown
attenuated proliferation and invasion by glioma cells and markedly decreased PCNA
and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown
suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased
phosphorylation of the c-src/FAK complex and its downstream signaling molecules,
Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic
target in the treatment of glioma.
PMID- 28422727
TI - MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer
cells through a Sp1 negative feedback loop.
AB - MicroRNAs have recently emerged as regulators of many biological processes
including cell proliferation, development and differentiation. This study
identified that miR-22 was statistically decreased in colorectal cancer clinical
specimens and highly metastatic cell lines. Moreover, low miR-22 expression was
associated with tumor metastasis, advanced clinical stage and relapse. Consistent
with clinical observations, miR-22 significantly suppressed the ability of
colorectal cancer cells to growth and metastasize in vitro and in vivo. Sp1 was
validated as a target of miR-22, and ectopic expression of Sp1 compromised the
inhibitory effects of miR-22. In addition, Sp1 repressed miR-22 transcription by
binding to the miR-22 promoter, hence forming a negative feedback loop. Further
study has shown that miR-22 suppresses the activity of PTEN/AKT pathway by Sp1.
Our present results implicate the newly indentified miR-22/Sp1/PTEN/AKT axis
might represent a potential therapeutic target for colorectal cancer.
PMID- 28422728
TI - Antimicrobial peptides with selective antitumor mechanisms: prospect for
anticancer applications.
AB - In the last several decades, there have been significant advances in anticancer
therapy. However, the development of resistance to cancer drugs and the lack of
specificity related to actively dividing cells leading to toxic side effects have
undermined these achievements. As a result, there is considerable interest in
alternative drugs with novel antitumor mechanisms. In addition to the recent
approach using immunotherapy, an effective but much cheaper therapeutic option of
pharmaceutical drugs would still provide the best choice for cancer patients as
the first line treatment. Ribosomally synthesized cationic antimicrobial peptides
(AMPs) or host defense peptides (HDP) display broad-spectrum activity against
bacteria based on electrostatic interactions with negatively charged lipids on
the bacterial surface. Because of increased proportions of phosphatidylserine
(negatively charged) on the surface of cancer cells compared to normal cells,
cationic amphipathic peptides could be an effective source of anticancer agents
that are both selective and refractory to current resistance mechanisms. We
reviewed herein the prospect for AMP application to cancer treatment, with a
focus on modes of action of cationic AMPs.
PMID- 28422729
TI - The relevance of a low JAK2V617F allele burden in clinical practice: a
monocentric study.
AB - Since low JAK2V617F allele burden (AB) has been detected also in healthy
subjects, its clinical interpretation may be challenging in patients with chronic
myeloproliferative neoplasms (MPNs). We tested 1087 subjects for JAK2V617F
mutation on suspicion of hematological malignancy. Only 497 (45.7%) patients were
positive. Here we present clinical and laboratory parameters of a cohort of
35/497 patients with an AB <= 3%.Overall, 22/35 (62.9%) received a WHO-defined
diagnosis of MPN and in 14/35 cases (40%) diagnosis was supported by bone marrow
(BM) histology (''Histology-based'' diagnosis). In patients that were unable or
refused to perform BM evaluation, diagnosis relied on prospective clinical
observation (12 cases, 34.3%) and molecular monitoring (6 cases, 17.1%)
(''Clinical-based'' or ''Molecular-based'' diagnosis, respectively). In 11/35
(31.4%) patients, a low JAK2V617F AB was not conclusive of MPN. The probability
to have a final hematological diagnosis (ET/PV/MF) was higher in patients with
thrombocytosis than in patients with polyglobulia (73.7% vs 57.1%, respectively).
The detection of AB >= 0.8% always corresponded to an overt MPN phenotype. The
repetition of JAK2V617F evaluation over time timely detected the spontaneous
expansion (11 cases) or reduction (4 cases) of JAK2V617F-positive clones and
significantly oriented the diagnostic process.Our study confirms that histology
is relevant to discriminate small foci of clonal hematopoiesis with uncertain
clinical significance from a full blown disease. Remarkably, our data suggest
that a cut-off of AB >= 0.8% is very indicative for the presence of a MPN.
Monitoring of the AB over time emerged as a convenient and non-invasive method to
assess clonal hematopoiesis expansion.
PMID- 28422731
TI - Risk of osteoporosis and pathologic fractures in cancer patients who underwent
hematopoietic stem cell transplantation: a nationwide retrospective cohort study.
AB - BACKGROUND: Long-term data on post-hematopoietic stem cell transplantation (HSCT)
osteoporosis and fracture are limited. This study evaluated the long-term risk of
osteoporosis and fracture in cancer patients who underwent HSCT. RESULTS: The
incidence density rate of osteoporosis was 12.5 per 1000 person-years in the HSCT
group, which was significantly higher than that in the non-HSCT group (5.65 per
1000 person-years) after adjustment for associated factors and consideration of
competing risk factors (adjusted subhazard ratio, 1.48; 95% confidence interval,
1.06-2.07). The incidence density rate of fracture was 4.89 per 1000 person-years
in the HSCT group, and the risk of fracture was 1.40 times higher in the HSCT
group than in the non-HSCT group (95% confidence interval, 0.83-2.40). The
vertebra was the most common site of fracture after HSCT (68.4%). The risk of
osteoporosis and fracture significantly increased in post-HSCT patients with both
hematological malignancies and solid tumors. Both autologous and allogeneic HSCTs
increased the risk of osteoporosis, whereas only autologous HSCT recipients had
an increased risk of fracture. MATERIALS AND METHODS: This nationwide
retrospective cohort study analyzed data from Taiwan's National Health Insurance
Research Database. We identified an HSCT group comprising 1040 cancer patients
who underwent HSCT during 2000-2008 and a non-HSCT group comprising 4160
propensity score-matched cancer patients who did not undergo HSCT. All patients
were followed up until the occurrence of osteoporosis; fracture; December 31,
2011; or withdrawal from the insurance program. CONCLUSIONS: HSCT recipients have
an increased risk of osteoporosis.
PMID- 28422730
TI - miR-133b, a particular member of myomiRs, coming into playing its unique
pathological role in human cancer.
AB - MicroRNAs, a family of single-stranded and non-coding RNAs, play a crucial role
in regulating gene expression at posttranscriptional level, by which it can
mediate various types of physiological and pathological process in normal
developmental progress and human disease, including cancer. The microRNA-133b
originally defined as canonical muscle-specific microRNAs considering their
function to the development and health of mammalian skeletal and cardiac muscles,
but new findings coming from our group and others revealed that miR-133b have
frequently abnormal expression in various kinds of human cancer and its complex
complicated regulatory networks affects the tumorigenicity and development of
malignant tumors. Very few existing reviews on miR-133b, until now, are
principally about its role in homologous cluster (miR-1, -133 and -206s),
however, most of constantly emerging new researches now are focused mainly on one
of them, so In this article, to highlight the unique pathological role of miR
133b playing in tumor, we conduct a review to summarize the current understanding
about one of the muscle-specific microRNAs, namely miR-133b, acting in human
cancer. The review focused on the following four aspects: the overview of miR
133b, the target genes of miR-133b involved in human cancer, the expression of
miR-133b and regulatory mechanisms leading to abnormal expression of miR-133b.
PMID- 28422733
TI - The transcriptional STAT3 is a potential target, whereas transcriptional
STAT5A/5B/6 are new biomarkers for prognosis in human breast carcinoma.
AB - Signal Transducer and Activators of Transcription (STAT) is a set of
transcription factors, involved in diverse cellular functions. Evidences from
cell lines, mouse models and human tissues implicate these transcription factors
in the oncogenesis of breast cancer. However, the diverse expression patterns and
prognostic values of 7 STATs remain to be elucidated. In the current study, we
mined the transcriptional and survival data of STATs in patients with breast
carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and
cBioPortal. It was found that STAT1/2 were up-regulated, whereas STAT3/4/5A/5B
were down-regulated in BC patients compared with the normal tissues. The
expressions of STAT5A/5B/6 were correlated with decreased levels of histological
differentiation. In survival analyses through the Kaplan-Meier plotter database,
high transcription levels of STAT2/4/5A/5B/6 were associated with better relapse
free survival (RFS) in all BC patients. Conversely, high STAT3 predicted shorter
RFS in BC patients, suggesting that STAT3 is potential targets for precision
therapy to BC patients. These data also provided STAT5A/5B/6 as new biomarker for
BC prognosis.
PMID- 28422732
TI - Molecular and serologic markers of HPV 16 infection are associated with local
recurrence in patients with oral cavity squamous cell carcinoma.
AB - Human papillomavirus (HPV) infections predict mortality in Taiwanese patients
with oral cavity squamous cell carcinoma (OCSCC). To address their prognostic
significance for local recurrence (LR), in this retrospective cohort study we
investigated different serologic and molecular markers of HPV 16 infection in 85
consecutive patients with primary OCSCC who received standard treatment and had
their sera stored before treatment. Resected tumor specimens were examined with
PCR-based assays for HPV 16 E6/E7 mRNA expression. Sera were tested with
suspension arrays for the presence of HPV-specific antibodies using synthetic L1
and E6 peptides as well as a synthetic E7 protein. HPV 16 E6/E7 mRNA, anti-L1,
anti-E6, and anti-E7 antibodies tested positive in 12%, 25%, 38%, and 41% of the
study patients, respectively. Multivariate analysis identified pathological
T3/T4, E6/E7 mRNA, and anti-E7 antibodies as independent risk factors for LR,
whereas anti-E6 antibodies were an independent protective factor. In patients
with >= 3 (high-risk group), 2 (intermediate-risk), and <= 1 (low-risk)
independent risk factors (predictors), the 5-year LR rates were 75%, 42%, and 4%,
respectively. Results were validated in an independent cohort. Together, our
preliminary data indicate that HPV 16 infections as well as low and high serum
levels of anti-E6 and anti-E7 antibodies, respectively, can serve as biomarkers
of LR in patients with OCSCC, whereas the clinical usefulness of anti-HPV 16
antibodies for risk stratification of newly diagnosed cases deserves further
scrutiny.
PMID- 28422734
TI - Silencing of karyopherin alpha2 inhibits cell growth and survival in human
hepatocellular carcinoma.
AB - Karyopherin alpha2 (KPNA2), involved in nucleocytoplasmic transport, has been
reported to be upregulated in hepatocellular carcinoma and considered as a
biomarker for poor prognosis. However, comprehensive studies of KPNA2 functions
in hepatocellular carcinogenesis are still lacking. Our study examine the roles
and related molecular mechanisms of KPNA2 in hepatocellular carcinoma
development. Results show that KPNA2 knockdown inhibited the proliferation and
growth of hepatocellular carcinoma cells in vitro and in vivo. KPNA2 knockdown
also inhibited colony formation ability, induced cell cycle arrest and cellular
apoptosis in two hepatocellular carcinoma cell lines, HepG2 and SMMC-7721.
Furthermore, gene expression microarray analysis in HepG2 cells with KPNA2
knockdown revealed that critical signaling pathways involved in cell
proliferation and survival were deregulated. In conclusion, this study provided
systematic evidence that KPNA2 was an essential factor promoting hepatocellular
carcinoma and unraveled potential molecular pathways and networks underlying
KPNA2-induced hepatocellular carcinogenesis.
PMID- 28422736
TI - Identification of MAP kinase pathways as therapeutic targets in gallbladder
carcinoma using targeted parallel sequencing.
AB - The aim of this study was to profile somatic mutation spectrum in gallbladder
cancers (GBCs), and determine the role of MAP kinase pathway in GBC by a series
of in vitro and in vivo studies. We performed targeted massively parallel
sequencing of DNA isolated from GBCs and matched blood from 14 GBC patients to
search for mutations in 504 genes commonly altered in human cancers. We
identified recurrent mutations enriched in several major signaling pathways
including MAP kinase, Wnt/beta-catenin and NF-kappaB pathways.
Immunohistochemistry analysis further validated overactivation of MAP kinase and
Wnt pathways in a panel of GBC samples. By treating GBC cells with MEK inhibitor
trametinib, we found that trametinib not only dramatically inhibited the activity
of MAPK/ERK pathway, but also blocked the Wnt/beta-catenin signaling through
decreasing beta-catenin expression or suppressing nucleus translocation of beta
catenin. Moreover, trametinib inhibited the proliferation of GBC cell in a dose-
and time-dependent manner, induced GBC cell apoptosis, and inhibited GBC cell
migration and invasion. Growth of xenograft tumors derived from GBC cell line NOZ
in nude mice was also significantly inhibited by trametinib. Our data highlight
the critical role of MAP kinase pathways in GBC pathogenesis, and may represent
therapeutic targets for this cancer.
PMID- 28422735
TI - Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as
an indicator for poor clinical outcome and tamoxifen resistance.
AB - The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog,
Bmi1, and Klf4, are known to be associated with stemness, epithelial-mesenchymal
transition and aggressive tumor behavior. This study was designed to evaluate the
clinicopathological significance of their expression in breast cancer.
Immunohistochemistry for Oct4, Sox2, Nanog, Bmi1, and Klf4 was performed in 319
cases of invasive breast cancer. The relationship between the expression of these
markers and clinicopathologic features of the tumors, including breast cancer
stem cell phenotype and epithelial-mesenchymal transition marker expression, and
their prognostic value in breast cancer, were analyzed. Expression of Oct4 and
Sox2 was commonly associated with high histologic grade and high Ki-67 index in
the whole group and in the hormone receptor-positive subgroup. On the other hand,
expression of Nanog, Bmi1, and Klf4 was inversely correlated with aggressive
features of the breast cancer. Oct4 expression was associated with ALDH1
expression but not with epithelial-mesenchymal transition marker expression. In
survival analysis, Oct4 expression was independently associated with poor
prognosis in the whole group and in the hormone receptor-positive subgroup, but
not in hormone receptor-negative subgroup. Particularly, Oct4 expression was
associated with poor clinical outcome in patients with hormone receptor-positive
breast cancer treated with tamoxifen. Our results indicate that Oct4 expression
is associated with aggressive features, ALDH1 expression, tamoxifen resistance
and poor clinical outcomes in hormone receptor-positive breast cancer, and thus
may be useful as a predictive and prognostic marker in this subgroup of breast
cancer.
PMID- 28422737
TI - Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9
mediated genome editing.
AB - Tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are effective
against lung adenocarcinomas harboring epidermal growth factor receptor (EGFR)
mutations. However, cancer cells can develop resistance to these agents with
prolonged exposure; in over 50% of cases, this is attributable to the EGFR T790M
mutation. Moreover, additional resistance mutations can arise with the use of new
drugs. Cancer cell lines with specific mutations can enable the study of
resistance mechanisms. In this study, we introduced the EGFR T790M mutation into
the PC9 human lung cancer cell line-which has a deletion in exon 19 of the EGFR
gene-by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated (Cas)9-mediated genome editing. EGFR pyrosequencing and peptide
nucleic acid clamping revealed that PC9 cells with EGFR T790M generated by
CRISPR/Cas 9 had a higher T790M mutation rate than those with the same mutation
generated by long-term exposure to gefitinib (PC9-G); moreover, resistance to
gefitinib in these clones was higher than that in PC9-G cells. The clones were
also highly sensitive to the 3rd-generation EGFR TKI AZD9291, which is cytotoxic
to lung cancer cells with EGFR T790M. The CRISPR/Cas9 programmable nuclease
system can be used to generate various cancer cell lines with specific mutations
that can facilitate studies on resistance mechanisms and drug efficacy.
PMID- 28422738
TI - Peripheral zone volume ratio (PZ-ratio) is relevant with biopsy results and can
increase the accuracy of current diagnostic modality.
AB - The current diagnostic modality of prostate cancer based on prostate specific
antigen (PSA) and systematic biopsy is far from ideal in terms of over-diagnosing
indolent prostate cancer and missing significant ones. Thus we integrated the
peripheral zone volume ratio (PZ-ratio) for diagnostic refinement. This
retrospective study included 247 consecutive patients who underwent initial
transrectal ultrasound-guided systematic prostate biopsy from April 2014 to
November 2015. Prostate volume was determined by semi-automatic contour on axial
T2 weighted magnetic resonance imaging (MRI). PZ-ratio was inversely correlated
with age (r = -0.36, p <0.0001). Adding PZ-ratio and MRI findings to the current
predictive model (age, PSA density, percent-free PSA) significantly increased
diagnostic accuracy in all patients (AUC: 0.871 vs. 0.812, p = 0.0059), but not
in patient subgroup with PSA 4-10 ng/ml (AUC: 0.863 vs. 0.803, p = 0.12). The new
model also significantly reduced the number of unnecessary biopsies while missing
less significant cancers at a probability threshold of 25%. PZ-ratio is a
potential tool in predicting biopsy results, and when added alone or in
combination with MRI findings, the diagnostic accuracy can be further enhanced.
PMID- 28422739
TI - Diagnostic role of Wnt pathway gene promoter methylation in non small cell lung
cancer.
AB - Wnt signal pathway genes are known to be involved with cancer development. Here
we tested the hypothesis whether DNA methylation of genes part of the Wnt
signaling pathway could help the diagnosis of non-small cell lung cancer (NSCLC).
The methylation levels of SFRP1, SFRP2, WIF1 and PRKCB in 111 NSCLC patients were
evaluated by quantitative methylation-specific PCR (qMSP). Promoter methylation
levels of four candidate genes were significantly higher in tumor tissues
compared with the adjacent tissues. SFRP1, SFRP2 and PRKCB genes were all shown
to be good predictors of NSCLC risk (SFRP1: AUC = 0.711; SFRP2: AUC = 0.631;
PRKCB: AUC = 0.650). The combined analysis showed that the methylation status of
the four genes had a sensitivity of 70.3% and a specificity of 73.9% in the
prediction of NSCLC risk for study cohort. A higher diagnostic value with an AUC
of 0.945 (95% CI: 0.923-0.967, sensitivity: 90.6%, specificity: 93.0%) was found
in TCGA cohort. In addition, SFRP1 and SFRP2 hypermethylation events were
specific to male patients. Further TCGA data mining analysis suggested that
SFRP1_cg15839448, SFRP2_cg05774801, and WIF1_cg21383810 were inversely associated
with the host gene expression. Moreover, GEO database analysis showed that 5'-Aza
deoxycytidine was able to upregulate gene expression in several lung cancer cell
lines. Subsequent dual-luciferase reporter assay showed a crucial regulatory
function of PRKCB promoter. In summary, our study showed that a panel of Wnt
signal pathway genes (SFRP1, SFRP2, WIF1 and PRKCB) had the potential as
methylation biomarkers in the diagnosis of NSCLC.
PMID- 28422740
TI - Involvement of miR-106b in tumorigenic actions of both prolactin and estradiol.
AB - Prolactin promotes a variety of cancers by an array of different mechanisms.
Here, we have investigated prolactin's inhibitory effect on expression of the
cell cycle-regulating protein, p21. Using a miRNA array, we identified a number
of miRNAs upregulated by prolactin treatment, but one in particular that was
strongly induced by prolactin and predicted to bind to the 3'UTR of p21 mRNA, miR
106b. By creating a p21 mRNA 3'UTR-luciferase mRNA construct, we demonstrated
degradation of the construct in response to prolactin in human breast, prostate
and ovarian cancer cell lines. Increased expression of miR-106b replicated, and
anti-miR-106b counteracted, the effects of prolactin on degradation of the 3'UTR
construct, p21 mRNA levels, and cell proliferation in breast (T47D) and prostate
(PC3) cancer cells. Increased expression of miR-106b also stimulated migration of
the very epithelioid T47D cell line. By contrast, anti-miR-106b dramatically
decreased expression of the mesenchymal markers, SNAIL-2, TWIST-2, VIMENTIN, and
FIBRONECTIN. Using signaling pathway inhibitors and the 3'UTR construct,
induction of miR-106b by prolactin was determined to be mediated through the
MAPK/ERK and PI3K/Akt pathways and not through Jak2/Stat5 in both T47D and PC3
cells. Prolactin activation of MAPK/ERK and PI3K/Akt also activates ERalpha in
the absence of an ERalpha ligand. 17beta-estradiol promoted degradation of the
construct in both cell lines and pre-incubation in the estrogen antagonist,
Fulvestrant, blocked the ability of both prolactin and 17beta-estradiol to induce
the construct-degrading activity. Together, these data support a convergence of
the prolactin and 17beta-estradiol miR-106b-elevating signaling pathways at
ERalpha.
PMID- 28422741
TI - Calmodulin promotes matrix metalloproteinase 9 production and cell migration by
inhibiting the ubiquitination and degradation of TBC1D3 oncoprotein in human
breast cancer cells.
AB - The hominoid oncoprotein TBC1D3 enhances growth factor (GF) signaling and GF
signaling, conversely, induces the ubiquitination and subsequent degradation of
TBC1D3. However, little is known regarding the regulation of this degradation,
and the role of TBC1D3 in the progression of tumors has also not been defined. In
the present study, we demonstrated that calmodulin (CaM), a ubiquitous cellular
calcium sensor, specifically interacted with TBC1D3 in a Ca2+-dependent manner
and inhibited GF signaling-induced ubiquitination and degradation of the
oncoprotein in both cytoplasm and nucleus of human breast cancer cells. The CaM
interacting site of TBC1D3 was mapped to amino acids 157~171, which comprises two
1-14 hydrophobic motifs and one lysine residue (K166). Deletion of these motifs
was shown to abolish interaction between TBC1D3 and CaM. Surprisingly, this
deletion mutation caused inability of GF signaling to induce the ubiquitination
and subsequent degradation of TBC1D3. In agreement with this, we identified
lysine residue 166 within the CaM-interacting motifs of TBC1D3 as the actual site
for the GF signaling-induced ubiquitination using mutational analysis. Point
mutation of this lysine residue exhibited the same effect on TBC1D3 as the
deletion mutant, suggesting that CaM inhibits GF signaling-induced degradation of
TBC1D3 by occluding its ubiquitination at K166. Notably, we found that TBC1D3
promoted the expression and activation of MMP-9 and the migration of MCF-7 cells.
Furthermore, interaction with CaM considerably enhanced such effect of TBC1D3.
Taken together, our work reveals a novel model by which CaM promotes cell
migration through inhibiting the ubiquitination and degradation of TBC1D3.
PMID- 28422742
TI - Multi-omics study revealing the complexity and spatial heterogeneity of tumor
infiltrating lymphocytes in primary liver carcinoma.
AB - Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC).
However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which
reflects one dimension of a tumor's spatial heterogeneity, and the relationship
between TIL diversity, local immune response and mutation burden remain
unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene
expression profiling analysis and whole-exome sequencing in parallel on five
regions of each tumor and on matched adjacent normal tissues and peripheral blood
from five PLC patients. A significantly higher cumulative frequency of the top
250 most abundant TIL clones was observed in tumors than in peripheral blood.
Besides, overlap rates of T cell receptor (TCR) repertoire for intratumor
comparisons, significant higher than those for tumor-adjacent normal tissue
comparisons and tumor-blood comparisons, which provide evidence for antigen
driven clonal expansion in PLC. Analysis of the percentage of ubiquitous TCR
sequences, regional frequencies of each clone and TIL diversity suggested TIL
clones varying between distinct regions of the same tumor, which indicated weak
TCR repertoire similarity within a single tumor. Furthermore, correlation
analysis revealed that TIL diversity significantly correlated with the expression
of immune response genes rather than the mutation load. We conclude that
intratumoural T-cell clones are spatially heterogeneous, which can lead to
underestimate the immune profile of PLC from a single biopsy sample and may
present challenge to adoptive cell therapy using autologous TILs. TIL diversity
provides a reasonable explanation for the degree of immune response, implied TIL
diversity can serve as a surrogate marker to monitor the effect of immunotherapy.
PMID- 28422746
TI - Integrating nanohybrid membranes of reduced graphene oxide: chitosan: silica sol
gel with fiber optic SPR for caffeine detection.
AB - Caffeine is the most popular psychoactive drug consumed in the world for
improving alertness and enhancing wakefulness. However, caffeine consumption
beyond limits can result in lot of physiological complications in human beings.
In this work, we report a novel detection scheme for caffeine integrating
nanohybrid membranes of reduced graphene oxide (rGO) in chitosan modified silica
sol gel (rGO: chitosan: silica sol gel) with fiber optic surface plasmon
resonance. The chemically synthesized nanohybrid membrane forming the sensing
route has been dip coated over silver coated unclad central portion of an optical
fiber. The sensor works on the mechanism of modification of dielectric function
of sensing layer on exposure to analyte solution which is manifested in terms of
red shift in resonance wavelength. The concentration of rGO in polymer network of
chitosan and silica sol gel and dipping time of the silver coated probe in the
solution of nanohybrid membrane have been optimized to extricate the supreme
performance of the sensor. The optimized sensing probe possesses a reasonably
good sensitivity and follows an exponentially declining trend within the entire
investigating range of caffeine concentration. The sensor boasts of an
unparalleled limit of detection value of 1.994 nM and works well in concentration
range of 0-500 nM with a response time of 16 s. The impeccable sensor methodology
adopted in this work combining fiber optic SPR with nanotechnology furnishes a
novel perspective for caffeine determination in commercial foodstuffs and
biological fluids.
PMID- 28422745
TI - Targeting of the breast cancer microenvironment with a potent and linkable
oxindole based antiangiogenic small molecule.
AB - The clinical efficacy of antiangiogenic small molecules (e.g., sunitinib) in
breast carcinoma has largely failed with substantial off-target toxicity. We
rationally designed and evaluated preclinically a novel sunitinib analogue, SAP,
with favourable pharmacological properties and the ability to be readily
conjugated to a targeting peptide or antibody for active tumour targeting.SAP was
evaluated in silico and in vitro in order to verify target engagement (e.g.,
VEGFR2). Pharmacokinetic and biodistribution parameters were determined in mice
using LC-MS/MS. SAP efficacy was tested in two breast cancer xenograft and two
syngeneic animal models and pharmacodynamic evaluation was accomplished using
phosphokinase assays and immunohistochemistry. Cardiac and blood toxicity of SAP
were also monitored.SAP retained the antiangiogenic and cytotoxic properties of
the parental molecule with an increased blood exposure and tumor accumulation
compared to sunitinib. SAP proved efficacious in all animal models. Tumors from
SAP treated animals had significantly decreased Ki-67 and CD31 markers and
reduced levels of phosphorylated AKT, ERK and S6 compared to vehicle treated
animals. In mice dosed with SAP there was negligible hematotoxicity, while
cardiac function measurements showed a reduction in the percentage left
ventricular fractional shortening compared to vehicle treated animals.In
conclusion, SAP is a novel rationally designed conjugatable small antiangiogenic
molecule, efficacious in preclinical models of breast cancer.
PMID- 28422747
TI - Controlled multiple neutral planes by low elastic modulus adhesive for flexible
organic photovoltaics.
AB - To protect brittle layers in organic photovoltaic devices, the mechanical neutral
plane strategy can be adopted through placing the brittle functional materials
close to the neutral plane where stress and strain are zero during bending.
However, previous research has been significantly limited in the location and
number of materials to protect through using a single neutral plane. In this
study, multiple neutral planes are generated using low elastic modulus adhesives
and are controlled through quantitative analyses in order to protect the multiple
brittle materials at various locations. Moreover, the protection of multiple
brittle layers at various locations under both concave and convex bending
directions is demonstrated. Multilayer structures that have soft adhesives are
further analyzed using the finite element method analysis in order to propose
guidelines for structural design when employing multiple neutral planes.
PMID- 28422748
TI - Therapeutic inhibition of soluble brain TNF promotes remyelination by increasing
myelin phagocytosis by microglia.
AB - Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which
remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are
important for remyelination in experimental MS models, but it is unknown whether
soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration
processes. Here, we investigated the specific contribution of solTNF to
demyelination and remyelination in the cuprizone model. Treatment with XPro1595,
a selective inhibitor of solTNF that crosses the intact blood-brain barrier
(BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss
and demyelination, but it permitted profound early remyelination due to improved
phagocytosis of myelin debris by CNS macrophages and prevented disease-associated
decline in motor performance. The beneficial effects of XPro1595 were absent in
TNF-deficient mice and replicated in tmTNF-knockin mice, showing that tmTNF is
sufficient for the maintenance of myelin and neuroprotection. These findings
demonstrate that solTNF inhibits remyelination and repair in a cuprizone
demyelination model and suggest that local production of solTNF in the CNS might
be one reason why remyelination fails in MS. These findings also suggest that
disinhibition of remyelination by selective inhibitors of solTNF that cross the
BBB might represent a promising approach for treatment in progressive MS.
PMID- 28422749
TI - Obesity-induced hepatic steatosis is mediated by endoplasmic reticulum stress in
the subfornical organ of the brain.
AB - Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation
of hepatic triglycerides, is a growing health epidemic. While ER stress in the
liver has been implicated in the development of NAFLD, the role of brain ER
stress - which is emerging as a key contributor to a number of chronic diseases
including obesity - in NAFLD remains unclear. These studies reveal that chemical
induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in
mice. Conversely, pharmacological reductions in brain ER stress in diet-induced
obese mice rescued NAFLD independent of body weight, food intake, and adiposity.
Evaluation of brain regions involved revealed robust activation of ER stress
biomarkers and ER ultrastructural abnormalities in the circumventricular
subfornical organ (SFO), a nucleus situated outside of the blood-brain-barrier,
in response to high-fat diet. Targeted reductions in SFO-ER stress in obese mice
via SFO-specific supplementation of the ER chaperone 78-kDa glucose-regulated
protein ameliorated hepatomegaly and hepatic steatosis without altering body
weight, food intake, adiposity, or obesity-induced hypertension. Overall, these
findings indicate a novel role for brain ER stress, notably within the SFO, in
the pathogenesis of NAFLD.
PMID- 28422750
TI - Differential expression of GPR15 on T cells during ulcerative colitis.
AB - G protein-coupled receptor 15 (GPR15) was recently highlighted as a colon-homing
receptor for murine and human CD4+ T cells. The aim of this study was to explore
the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and
effector T cells (Teffs), and to determine whether GPR15 is the driver for the
migration of T cells to the colon during ulcerative colitis (UC). In the
peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell
subsets produced less IFN-gamma and IL-4 but more IL-17 after stimulation and
showed a higher migration activity compared with GPR15-CD4+ T cells. In UC
patients, GPR15 expression was increased on Tregs in the peripheral blood but not
on Teffs. Interestingly, the expression of GPR15 was significantly enhanced on
colonic T cells of UC patients in noninflamed biopsies but not in inflamed
biopsies. The differential expression of GPR15 in UC patients was accompanied by
a significant reduction of bacterial immunoregulatory metabolites in the feces.
In conclusion, GPR15 expression on CD4+ T cells is altered in UC patients, which
may have implications for the development of therapeutic approaches to target T
cell trafficking to the colon.
PMID- 28422751
TI - Twelve-year survival and immune correlates in dendritic cell-vaccinated melanoma
patients.
AB - BACKGROUND: Reports on long-term (>=10 years) effects of cancer vaccines are
missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous
melanoma patients to further explore the immunogenicity of our DC vaccine and to
establish its long-term toxicity and clinical benefit after a planned 10-year
followup. METHODS: Monocyte-derived DCs matured by TNFalpha, IL-1beta, IL-6, and
PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides
were injected intradermally in high doses over 2 years. We performed serial
immunomonitoring in all 53 evaluable patients. RESULTS: Vaccine-specific immune
responses including high-affinity, IFNgamma-producing CD4+ and lytic
polyfunctional CD8+ T cells were de novo induced or boosted in most patients.
Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not
further enhance such immune responses, while keyhole limpet hemocyanin (KLH)
pulsing to provide unspecific CD4+ help promoted CD8+ T cell responses - notably,
their longevity. An unexpected 19% of nonresectable metastatic melanoma patients
are still alive after 11 years, a survival rate similar to that observed in
ipilimumab-treated patients and achieved without any major (>grade 2) toxicity.
Survival correlated significantly with the development of intense vaccine
injection site reactions, and with blood eosinophilia after the first series of
vaccinations, suggesting that prolonged survival was a consequence of DC
vaccination. CONCLUSIONS: Long-term survival in advanced melanoma patients
undergoing DC vaccination is similar to ipilimumab-treated patients and occurs
upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine
injection site reactions occurring after the initial vaccinations. TRIAL
REGISTRATION: ClinicalTrials.gov NCT00053391. FUNDING: European Community, Sixth
Framework Programme (Cancerimmunotherapy LSHC-CT-2006-518234; DC-THERA LSHB-CT
2004-512074), and German Research Foundation (CRC 643, C1, Z2).
PMID- 28422752
TI - T-bet+ B cells are induced by human viral infections and dominate the HIV gp140
response.
AB - Humoral immunity is critical for viral control, but the identity and mechanisms
regulating human antiviral B cells are unclear. Here, we characterized human B
cells expressing T-bet and analyzed their dynamics during viral infections. T
bet+ B cells demonstrated an activated phenotype, a distinct transcriptional
profile, and were enriched for expression of the antiviral immunoglobulin
isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and
vaccinia virus vaccinations and also during early acute HIV infection. Viremic
HIV-infected individuals maintained a large T-bet+ B cell population during
chronic infection that was associated with increased serum and cell-associated
IgG1 and IgG3 expression. The HIV gp140-specific B cell response was dominated by
T-bet-expressing memory B cells, and we observed a concomitant biasing of gp140
specific serum immunoglobulin to the IgG1 isotype. These findings suggest that T
bet induction promotes antiviral immunoglobulin isotype switching and development
of a distinct T-bet+ B cell subset that is maintained by viremia and coordinates
the HIV Env-specific humoral response.
PMID- 28422753
TI - Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary
aldosteronism.
AB - BACKGROUND: Adrenal aldosterone excess is the most common cause of secondary
hypertension and is associated with increased cardiovascular morbidity. However,
adverse metabolic risk in primary aldosteronism extends beyond hypertension, with
increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which
cannot be easily explained by aldosterone excess. METHODS: We performed mass
spectrometry-based analysis of a 24-hour urine steroid metabolome in 174 newly
diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71
bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56
patients with endocrine inactive adrenal adenoma, 104 patients with mild
subclinical, and 47 with clinically overt adrenal cortisol excess. We also
analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing
CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing
adenoma, employing immunohistochemistry with digital image analysis. RESULTS:
Primary aldosteronism patients had significantly increased cortisol and total
glucocorticoid metabolite excretion (all P < 0.001), only exceeded by
glucocorticoid output in patients with clinically overt adrenal Cushing syndrome.
Several surrogate parameters of metabolic risk correlated significantly with
glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression
was significantly associated with the corresponding in vivo glucocorticoid
excretion. Unilateral adrenalectomy resolved both mineralocorticoid and
glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found
in 13 (29%) of 45 consecutively tested patients. CONCLUSION: Our data indicate
that glucocorticoid cosecretion is frequently found in primary aldosteronism and
contributes to associated metabolic risk. Mineralocorticoid receptor antagonist
therapy alone may not be sufficient to counteract adverse metabolic risk in
medically treated patients with primary aldosteronism. FUNDING: Medical Research
Council UK, Wellcome Trust, European Commission.
PMID- 28422754
TI - MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial
infections.
AB - Perforin-2 is a highly conserved pore-forming protein encoded by macrophage
expressed gene 1 (MPEG1). A number of studies have shown that Perforin-2
deficient mice are unable to survive following a bacterial challenge that is
nonlethal in WT mice. There is also recent evidence that Mpeg1+/- heterozygous
mice display an intermediate killing ability compared with Mpeg1 WT and Mpeg1-/-
mice. Despite these in vivo findings, to date, no perforin-2 deficiencies have
been associated with human disease. Here, we report four patients with persistent
nontuberculous mycobacterial infection who had heterozygous MPEG1 mutations. In
vitro, neutrophils, macrophages, and B cells from these patients were unable to
kill Mycobacterium avium as efficiently as normal controls. CRISPR mutagenesis
validated the deleterious antibacterial activity of these mutations. These data
suggest that perforin-2 haploinsufficiency may contribute to human susceptibility
to infections with intracellular bacteria.
PMID- 28422755
TI - beta-Klotho deficiency protects against obesity through a crosstalk between
liver, microbiota, and brown adipose tissue.
AB - beta-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and
FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of
pharmacological FGF21 treatment including stimulation of glucose utilization and
thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on
high-fat diet in order to better understand the consequences of abrogating both
endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly,
Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy
expenditure and BAT activity. Klb-/- mice exhibited not only an increase but also
a shift in bile acid (BA) composition featured by activation of the classical
(neutral) BA synthesis pathway at the expense of the alternative (acidic)
pathway. High hepatic production of cholic acid (CA) results in a large excess of
microbiota-derived deoxycholic acid (DCA). DCA is specifically responsible for
activating the TGR5 receptor that stimulates BAT thermogenic activity. In fact,
combined gene deletion of Klb and Tgr5 or antibiotic treatment abrogating
bacterial conversion of CA into DCA both abolish DIO resistance in Klb-/- mice.
These results suggested that DIO resistance in Klb-/- mice is caused by high
levels of DCA, signaling through the TGR5 receptor. These data also demonstrated
that gut microbiota can regulate host thermogenesis via conversion of primary
into secondary BA. Pharmacologic or nutritional approaches to selectively
modulate BA composition may be a promising target for treating metabolic
disorders.
PMID- 28422756
TI - beta-catenin and PI3Kdelta inhibition expands precursor Th17 cells with
heightened stemness and antitumor activity.
AB - ICOS costimulation generates Th17 cells with durable memory responses to tumor.
Herein, we found that ICOS induces PI3K/p110delta/Akt and Wnt/beta-catenin
pathways in Th17 cells. Coinhibiting PI3Kdelta and beta-catenin altered the
biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed
less RORgammat, which, in turn, reduced their ability to secrete IL-17.
Unexpectedly, these cells were more effective (than uninhibited cells) at
regressing tumor when infused into mice, leading to long-term curative responses.
PI3Kdelta inhibition expanded precursor Th17 cells with a central memory
phenotype that expressed nominal regulatory properties (low FoxP3), while beta
catenin inhibition enhanced Th17 multifunctionality in vivo. Remarkably, upon TCR
restimulation, RORgammat and IL-17 rebounded in Th17 cells treated with PI3Kdelta
and beta-catenin inhibitors. Moreover, these cells regained beta-catenin, Tcf7,
and Akt expression, licensing them to secrete heightened IL-2, persist, and
eradicate solid tumors without help from endogenous NK and CD8 T cells. This
finding shines a light on ways to repurpose FDA-approved drugs to augment T cell
based cancer immunotherapies.
PMID- 28422757
TI - Cross-reactive dengue human monoclonal antibody prevents severe pathologies and
death from Zika virus infections.
AB - Zika virus (ZIKV) infections have been linked with neurological complications and
congenital Zika syndrome. Given the high level of homology between ZIKV and the
related flavivirus dengue virus (DENV), we investigated the level of cross
reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs
showed binding to ZIKV virions, with several exhibiting neutralizing capacities
against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to
recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved
fusion-loop peptide, a conformation-specific epitope on the E monomer, and a
quaternary epitope on the virion surface. The most potent ZIKV-neutralizing mAb
(SIgN-3C) was assessed in 2 type I interferon receptor-deficient (IFNAR-/-) mouse
models of ZIKV infection. Treatment of adult nonpregnant mice with SIgN-3C
rescued mice from virus-induced weight loss and mortality. The SIgN-3C variant
with Leu-to-Ala mutations in the Fc region (SIgN-3C-LALA) did not induce antibody
dependent enhancement (ADE) in vitro but provided similar levels of protection in
vivo. In pregnant ZIKV-infected IFNAR-/- mice, treatment with SIgN-3C or SIgN-3C
LALA significantly reduced viral load in the fetal organs and placenta and
abrogated virus-induced fetal growth retardation. Therefore, SIgN-3C-LALA holds
promise as a ZIKV prophylactic and therapeutic agent.
PMID- 28422758
TI - First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR
antibody cetuximab in advanced cancer patients.
AB - BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti
EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR
sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC).
METHODS: Utilizing a standard 3+3 design, a phase I study was designed to
determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities
(DLTs) of the regorafenib plus cetuximab combination among patients with advanced
cancer including CRC. Comprehensive genomic profiling was performed on the
exceptional responder. RESULTS: Among the 27 patients enrolled the median age was
54 years. None of 19 patients treated at dose level 1 (cetuximab i.v. 200 mg/m2
followed by 150 mg/m2 weekly + regorafenib 80 mg daily) experienced a DLT, and 2
of 5 patients treated at dose level 2 (cetuximab i.v. 200 mg/m2 followed by 150
mg/m2 weekly + regorafenib 120 mg daily) experienced a DLT (grade 3
thrombocytopenia [n = 1] and grade 3 intra-abdominal bleed [n = 1]). Most common
adverse events were grade 1 or 2 rash (20 patients). Of 24 evaluable patients, 11
(46%) patients had clinical benefit (stable disease > 6 cycles or partial
response [PR]) (CRC n = 8, one patient each with head and neck cancer, carcinoma
of unknown primary, and glioblastoma). A CRC patient, who progressed on anti-EGFR
and regorafenib, achieved a PR (46% decrease per RECIST v1.1) lasting 15 months.
Genomic profiling of an exceptional responder with response for over 27 cycles
revealed hypermutated genotype with microsatellite instability (MSI). CONCLUSION:
Regorafenib 80 mg daily plus cetuximab 200 mg/m2 loading dose, followed by 150
mg/m2 every week is the MTD/recommended phase II dose. The combination
demonstrated early signals of activity in wild-type CRC, including 1 exceptional
responder with MSI high. TRIAL REGISTRATION: clinicaltrials.gov
NCT02095054FUNDING. The University of Texas MD Anderson Cancer Center is
supported by the NIH Cancer Center Support Grant CA016672. This work was
supported in part by the Cancer Prevention Research Institute of Texas grant
RP110584 and National Center for Advancing Translational Sciences grant UL1
TR000371 (Center for Clinical and Translational Sciences).
PMID- 28422759
TI - RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces
bradycardia by disturbing the coupled clock pacemaker mechanism.
AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic
arrhythmia that manifests syncope or sudden death in children and young adults
under stress conditions. CPVT patients often present bradycardia and sino-atrial
node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN
function in two CPVT families and in a novel knock-in (KI) mouse model carrying
the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate.
Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was
slower in KI mouse SAN preparations than in WT, without any significant
alteration in the "funny" current (If ). The L-type Ca2+ current was reduced in
KI SAN cells in a [Ca2+]i-dependent way, suggesting that bradycardia was due to
disrupted crosstalk between the "voltage" and "Ca2+" clock, and the mechanisms of
pacemaking was induced by aberrant spontaneous RyR2- dependent Ca2+ release. This
finding was consistent with a higher Ca2+ leak during diastolic periods produced
by long-lasting Ca2+ sparks in KI SAN cells. Our results uncover a mechanism for
the CPVT-causing RyR2 N-terminal mutation R420Q, and they highlight the fact that
enhancing the Ca2+ clock may slow the heart rhythm by disturbing the coupling
between Ca2+ and voltage clocks.
PMID- 28422760
TI - Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of
idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without
effective treatment, highlighting the need for identifying new targets and
treatment modalities. The pathogenesis of IPF is complex, and engaging multiple
targets simultaneously might improve therapeutic efficacy. To assess the role of
the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF
and its interaction with inducible nitric oxide synthase (iNOS) as dual
therapeutic targets, we analyzed lung fibrosis and the status of the
endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary
fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from
patients with IPF, as well as controls. In addition, we investigated the
antifibrotic efficacy in the mouse PF model of an orally bioavailable and
peripherally restricted CB1R/iNOS hybrid inhibitor. We report that increased
activity of the endocannabinoid/CB1R system parallels disease progression in the
lungs of patients with idiopathic PF and in mice with bleomycin-induced PF and is
associated with increased tissue levels of interferon regulatory factor-5.
Furthermore, we demonstrate that simultaneous engagement of the secondary target
iNOS by the hybrid CB1R/iNOS inhibitor has greater antifibrotic efficacy than
inhibition of CB1R alone. This hybrid antagonist also arrests the progression of
established fibrosis in mice, thus making it a viable candidate for future
translational studies in IPF.
PMID- 28422761
TI - Topological length of white matter connections predicts their rate of atrophy in
premanifest Huntington's disease.
AB - We lack a mechanistic explanation for the stereotyped pattern of white matter
loss seen in Huntington's disease (HD). While the earliest white matter changes
are seen around the striatum, within the corpus callosum, and in the posterior
white matter tracts, the order in which these changes occur and why these white
matter connections are specifically vulnerable is unclear. Here, we use diffusion
tractography in a longitudinal cohort of individuals yet to develop clinical
symptoms of HD to identify a hierarchy of vulnerability, where the topological
length of white matter connections between a brain area and its neighbors
predicts the rate of atrophy over 24 months. This demonstrates a new principle
underlying neurodegeneration in HD, whereby brain connections with the greatest
topological length are the first to suffer damage that can account for the
stereotyped pattern of white matter loss observed in premanifest HD.
PMID- 28422762
TI - Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to
myofibroblast transformation.
AB - Secreted modular calcium-binding protein 2 (SMOC2) belongs to the secreted
protein acidic and rich in cysteine (SPARC) family of matricellular proteins
whose members are known to modulate cell-matrix interactions. We report that
SMOC2 is upregulated in the kidney tubular epithelial cells of mice and humans
following fibrosis. Using genetically manipulated mice with SMOC2 overexpression
or knockdown, we show that SMOC2 is critically involved in the progression of
kidney fibrosis. Mechanistically, we found that SMOC2 activates a fibroblast-to
myofibroblast transition (FMT) to stimulate stress fiber formation,
proliferation, migration, and extracellular matrix production. Furthermore, we
demonstrate that targeting SMOC2 by siRNA results in attenuation of TGFbeta1
mediated FMT in vitro and an amelioration of kidney fibrosis in mice. These
findings implicate that SMOC2 is a key signaling molecule in the pathological
secretome of a damaged kidney and targeting SMOC2 offers a therapeutic strategy
for inhibiting FMT-mediated kidney fibrosis - an unmet medical need.
PMID- 28422763
TI - A modifier screen identifies DNAJB6 as a cardiomyopathy susceptibility gene.
PMID- 28422764
TI - 3D pulmospheres serve as a personalized and predictive multicellular model for
assessment of antifibrotic drugs.
PMID- 28422765
TI - Foreign Body Type Nasal Pseudocyst After Augmentation Rhinoplasty:
Histopathologically Mucin-Containing Pseudocyst.
PMID- 28422766
TI - An Immunoscore Using PD-L1, CD68, and Tumor-infiltrating Lymphocytes (TILs) to
Predict Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer.
AB - Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is
partly regulated by the immune microenvironment. We evaluated immune checkpoint
PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and
stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and
correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy
biopsies with >30% TILs were considered lymphocyte-rich IBC. We performed
immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing >1% PD-L1+
immune or tumor cells were considered positive. CD68 was positive if >40% of
tumor stroma contained CD68+ cells or atleast 50% of tumor cells showed
infiltration by CD68+ cells. Residual Cancer burden (RCB) Score of 0/I
represented excellent response to NAC and RCB II or III unfavorable response.
Thirty-five patients had RCB 0/I and 41 pts RCB II/ III. TILs>30% were present in
prechemotherapy biopsies in 19 pts of whom 14 showed RCB 0/I (P=0.0075). Twenty
seven cases were PD-L1+ and 20 had an RCB 0/I (P=0.0003). Twenty-two cases were
CD68+ of whom 18 showed RCB 0/I (P=<0.0001) There was a significant association
between TILs>30%, PD-L1+ and CD68+ expression. Using atleast one of these
immunologic parameters identified 26 of 35 patients with RCB 0/I and showed a
higher sensitivity for response prediction than TILs alone (40% vs. 74.3%). In
conclusion we demonstrate that high numbers of CD68+ monocytic/macrophage cells
and PD-L1 expression in IBC shows significant association with NAC response. An
immune biomarker profile including TILs, PD-LI and CD68 is more sensitive for NAC
response prediction than TILs alone.
PMID- 28422767
TI - Pseudolaric acid B induces endometrial cancer Ishikawa cell apoptosis and
inhibits metastasis through AKT-GSK-3beta and ERK1/2 signaling pathways.
AB - Pseudolaric acid B (PAB) is the most active constituent extracted from the bark
of Pseudolarix kaempferi, which has been used as an antifungal remedy in
traditional Chinese medicine. It is reported to have cytotoxicity to many tumor
cell lines. In this study, we investigated the effects of PAB against human
endometrial cancer Ishikawa cells. We found that PAB inhibited Ishikawa cell
proliferation, and induced cell apoptosis and G2/M phase arrest through a
mechanism involving AKT-GSK-3beta and ERK1/2 signaling pathways. PAB also
suppressed the Ishikawa cell adhesion, invasion, migration, and colony formation
ability by increasing the expression of E-cadherin, Ezrin, and Kiss-1, and
decreasing the expression of matrix metalloproteinase-9 and vascular endothelial
growth factor. Taken together, these data indicated that PAB can be expected to
be a novel treatment agent for endometrial cancer therapy.
PMID- 28422769
TI - Visual Outcomes and Local Control After Fractionated Stereotactic Radiotherapy
for Optic Nerve Sheath Meningioma.
AB - PURPOSE: To review the outcomes of patients with optic nerve sheath meningiomas
(ONSM) treated with fractionated stereotactic radiotherapy. METHODS: Patient
characteristics, treatment, and outcomes were analyzed for all patients with
primary and secondary ONSM treated from 2001 to 2012. Clinically significant
visual acuity change was defined as a 2-line change on the Snellen eye chart from
pre-fractionated stereotactic radiotherapy. RESULTS: Forty-one patients were
treated: 23 patients with primary ONSM and 18 patients with secondary ONSM. The
median age at diagnosis was 56 years. The median visual follow up was 3.8 years
and the median radiologic follow up was 4.4 years. At diagnosis, 36% had normal
vision (20/20-20/40), 10% had mild impairment (<20/40-20/60), 20% had moderate
visual impairment (<20/60-20/200), 27% had severe impairment (<20/200), and 7%
had no light perception. Common acute side effects were headache (32%) and nausea
(15%); 15% of patients required corticosteroids during stereotactic radiotherapy.
Chronic toxicities included retinopathy (7%), pituitary dysfunction (13%),
chronic ocular pain (5%), and cataracts (2%). Visual acuity was stable in 65%,
improved in 27%, and decreased in 8% of patients. Visual fields were stable in
70%, improved in 21%, and reduced in 9%. Actuarial 5-year local control rates
were 100% for primary ONSM and 88% for secondary ONSM. Actuarial 5-year visual
preservation rates were 100% for primary ONSM and 86% for secondary ONSM.
CONCLUSIONS: Fractionated stereotactic radiotherapy for primary and secondary
ONSM was well tolerated and provides excellent local control and visual
preservation. Longer follow up is required to determine the risk of late ocular
and pituitary sequelae.
PMID- 28422770
TI - Technical Alterations during an Incremental Field Test in Elite Male Tennis
Players.
AB - PURPOSE: We investigated technical and physiological responses along with their
relationships during an incremental field test to exhaustion specific to tennis
(TEST) in elite players. METHODS: Twenty male elite tennis players completed
TEST, which consisted of hitting alternatively forehand and backhand strokes at
increasing ball frequency (ball machine) every minute. Ball accuracy (BA), ball
velocity (BV), and tennis performance (TP) index (TP = BA * BV) were determined
by radar and video analysis for each stroke, in addition to cardiorespiratory
responses and blood lactate concentrations. RESULTS: At low intensities (less
than 80% of maximal oxygen uptake [VO2max]), technical performance was steady.
From 80% to 100% of VO2max, significant and steady decreases in BV (-9.0% and
13.3%; P = 0.02 and P = 0.002), BA (-19.4% and -18.4%; both P < 0.001), and TP (
27.4% and -29.15%; both P = 0.002) occurred for forehands and backhands,
respectively. Changes in TP and blood lactate concentration from 60% to 100% of
VO2max were inversely correlated (r = -0.51, P = 0.008). BV was 5.2% higher (P =
0.042) for forehand versus backhand, and there was no difference between strokes
for both BA (P = 0.930) and TP (P = 0.536). CONCLUSION: Technical alterations
(i.e., decrease in BV, BA, and TP) in elite players undergoing TEST only occurred
at high intensity (>80% of VO2max), presumably because of the use of compensatory
strategies to overcome fatigue. Above this intensity, all technical indices
decreased steadily until exhaustion, independently of the stroke nature.
PMID- 28422771
TI - Slow Intermuscular Oscillations are Associated with Cocontraction Steadiness.
AB - PURPOSE: Voluntary muscle contraction often involves low-frequency correlated
neural oscillations across muscles, which may degrade steady cocontraction
between antagonistic muscles with distinct levels of activation per each muscle
(unbalanced cocontraction). The purposes of the study were 1) to determine
whether there is an association between the low-frequency correlated EMG
oscillations and the performance of steady unbalanced cocontraction across
individuals and 2) to determine whether a bout of out-of-phase cocontraction
practice reduces the in-phase low-frequency correlated neural oscillations and
improves the performance of steady unbalanced cocontraction. METHODS: Healthy
young adults were divided into three intervention groups: cocontraction,
contraction, and control. All participants were tested for unbalanced steady
cocontractions with antagonistic muscles about the elbow joint before and after a
bout of intervention with the visual feedback of surface EMG. During the
intervention period, the cocontraction group practiced an out-of-phase
cocontraction, whereas the contraction group practiced agonist contractions.
RESULTS: Mean squared error and variance of EMG amplitude were positively
correlated with low-frequency EMG coherence <3 Hz across subjects, which became
more prevalent after the intervention period. There was no specific effect of the
cocontraction intervention on these variables. CONCLUSION: These findings suggest
that individuals with less low-frequency correlated neural oscillations tend to
perform steady cocontraction more skillfully, and the low-frequency correlated
oscillations may not be acutely modulated by one bout of out-of-phase
cocontraction practice.
PMID- 28422772
TI - Can Ultrasound Imaging Predict the Success of an Experimental Steatofibrosis
Model?
AB - Our goal was to evaluate the role of ultrasound (US) imaging in an experimental 2
hit steatofibrosis rat model. Nineteen female Sprague-Dawley rats were divided
into 2 groups: control group (n = 6) and high-fat diet carbontetrachloride (HFD
CCl4) group (n = 13) that was fed with HFD for 14 weeks. Ultrasound was performed
to evaluate liver steatosis. The HFD-CCl4 group rats were divided further into 2
subgroups: HFD rats with liver steatosis [US (+) group; n = 6] and without
steatosis [US (-) group; n = 7]. All rats in the subgroups were administered with
CCl4. In both US (+) and US (-) subgroups, steatosis score, fibrosis score,
triglyceride, and hydroxyproline contents were markedly higher compared with the
control group. When compared with the US (-) group, triglyceride and
hydroxyproline contents were significantly higher in the US (+) group, whereas
steatosis and fibrosis scores were not different. Ultrasound imaging may be
useful to assess the success of a 2-hit experimental steatofibrosis model.
PMID- 28422773
TI - Infections in rheumatoid arthritis.
AB - PURPOSE OF REVIEW: The purpose of this review is to provide an update concerning
recent advances in the evidence- based study of serious infections in patients
with rheumatoid arthritis (RA) treated with biological drugs or conventional
disease-modifying antirheumatic drugs (DMARDs), concentrating on studies
published in the last 18 months. RECENT FINDINGS: New studies have further
strengthened existing evidence relating the use of biological drugs to serious
infections. The risk does not seem to be any different with short-term or long
term use. There is still a lack of conclusive studies identifying biomarkers, but
it is plausible that the drugs have direct effects on cytokines and cell activity
and then serious infections. SUMMARY: The frequent infections of patients with RA
may be due to the disease itself (altered immunological function, disability,
immobility, joint surgery), extra-articular manifestations or DMARDs,
immunosuppressants and steroids. The use of biological drugs lead to the
development of serious infections including tuberculosis. Patients should be
informed of their increased risk, and physicians need to be aware of these
complications and how to treat them.
PMID- 28422774
TI - Squamous Cellular Carcinoma Antigen Serum Determination as a Biomarker of Barrett
Esophagus and Esophageal Cancer: A Phase III Study.
AB - GOAL: To evaluate the potential role of the determination of the immunocomplexed
form of squamous cell carcinoma antigen [SCCA-immunoglobulin (Ig)M] for the
screening of Barrett esophagus (BE) and esophageal adenocarcinoma (EAC).
BACKGROUND: The cost-effectiveness of surveillance in BE is still debated and the
use of biomarkers in screening and surveillance still not recommended. No
information is available regarding SCCA-IgM determination in BE. STUDY: SCCA-IgM
levels were determined (enzyme-linked immunosorbent assay) in 231 patients
prospectively recruited, 71 with BE, 53 with EAC, and 107 controls, including 42
blood donors and 65 patients with gastroesophageal reflux. SCCA-IgM cutoffs
between BE/EAC and controls and for BE "at risk" versus short nondysplastic BE
were calculated by receiver operating characteristic curves. Immunostaining for
SCCA-IgM was obtained in a subgroup of patients. RESULTS: Median SCCA-IgM values
were significantly higher in BE and EAC than in controls (P=0.0001). Patients
with SCCA-IgM levels above the cutoff had a 33 times higher relative risk of
harboring BE or EAC (P=0.0001). Patients "at risk," with long or dysplastic BE
had SCCA-IgM levels significantly higher than those with short nondysplastic BE
(P=0.035) and patients with SCCA-IgM above the cutoff had a 8 times higher
relative risk of having BE "at risk." SCCA was expressed in Barrett mucosa but
not in cardiac metaplasia. CONCLUSIONS: Serum SCCA-IgM determination allows the
identification of patients at risk for BE/EAC and the stratification of BE
patients in subgroups with different cancer risk. Because of the still limited
number of controls, large, prospective studies are required to confirm this
evidence.
PMID- 28422776
TI - Lower Cranial Nerves Paralysis Following Prone-Position Mechanical Ventilation.
AB - OBJECTIVE: To communicate a complication of prone-position ventilation. DATA
SOURCES: Case history. STUDY SELECTION: Case report. DATA EXTRACTION AND DATA
SYNTHESIS: Clinical information from medical record. CONCLUSIONS: This is a very
infrequent cause of dysphagia following prone-position ventilation.
PMID- 28422775
TI - A Contemporary Assessment of Acute Mechanical Ventilation in Beijing:
Description, Costs, and Outcomes.
AB - OBJECTIVE: To evaluate the contemporary practice, outcomes, and costs related to
mechanical ventilation among ICUs in China. DESIGN: A prospective observational
cohort study. SETTING: Fourteen ICUs among 13 hospitals in Beijing, China.
PATIENTS: Seven hundred ninety-three patients who received at least 24 hours of
mechanical ventilation within the first 48 hours of ICU stay. INTERVENTION: None.
MEASUREMENTS AND RESULTS: The mean age was 64 years. Sixty-three percent were
male. New acute respiratory failure accounted for 85.5% of mechanical ventilation
cases. Only 4.7% of the patients received mechanical ventilation for acute
exacerbation of chronic obstructive pulmonary disease. The most widely used
ventilation mode was the combination of synchronized intermittent mandatory
ventilation and pressure support (43.6%). Use of lung-protective ventilation is
widespread with tidal volumes of 7.1 mL/kg (2.1 mL/kg). The ICU/hospital
mortality was 27.6%/29.3%, respectively (8.5%/9.7% for surgical patients and
41.3%/43.2% for medical patients, respectively). The mean level of ICU/hospital
cost per patient was $15,271 (18,940)/$22,946 (25,575), respectively. The mean
daily ICU cost per patient was $1,212. CONCLUSION: For the first time, we
obtained a preliminary epidemiology data of mechanical ventilation in Beijing,
China, through the study. Compared with the other nations, our patients are
older, predominantly male, and treated according to prevailing international
guidelines yet at a relatively high cost and high mortality. The expanding
elderly population predicts increase demand for mechanical ventilation that must
be met by continuous improvement in quality and efficiency of critical care
services.
PMID- 28422777
TI - Population-Based Epidemiology of Sepsis in a Subdistrict of Beijing.
AB - OBJECTIVE: Information about the epidemiology of sepsis in community residents in
China remains scarce and incomplete. The purpose of this study was to describe
the occurrence rate and outcome of sepsis in Yuetan Subdistrict of Beijing and to
estimate the occurrence rate of sepsis in China. DESIGN: Retrospective cohort
study. SETTING: All public hospitals serving residents in Yuetan Subdistrict,
Beijing. PATIENTS: All patients (n = 1,716) meeting criteria for sepsis based on
American College of Chest Physicians/Society of Critical Care Medicine consensus
definition. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We screened all
adult residents in Yuetan Subdistrict who were hospitalized from July 1, 2012, to
June 30, 2014, and reviewed medical records. Patients with sepsis were included
in the analysis. We enrolled 1,716 patients with sepsis out of 21,191
hospitalized adults screened, among whom severe sepsis developed in 256 patients,
and septic shock developed in 233 patients. The crude annual occurrence rates of
sepsis, severe sepsis, and septic shock in Yuetan Subdistrict were 667, 103, and
91 cases per 100,000 population, corresponding to standardized occurrence rates
of 461, 68, and 52 cases per 100,000 population per year, respectively. Both
occurrence rate and mortality increased significantly with age, although males
had higher age-adjusted occurrence rate and mortality. The occurrence rate of
sepsis also exhibited seasonal variation, peaking in winter season. The overall
hospital mortality rate of sepsis was 20.6%, yielding a standardized mortality
rate of 79 cases per 100,000 population per year. CONCLUSIONS: Sepsis is a common
and frequently fatal syndrome in Yuetan Subdistrict, Beijing. The occurrence rate
and mortality of sepsis are significantly higher in males and elderly people.
PMID- 28422778
TI - Ultrasound as a Screening Tool for Central Venous Catheter Positioning and
Exclusion of Pneumothorax.
AB - OBJECTIVES: Although real-time ultrasound guidance during central venous catheter
insertion has become a standard of care, postinsertion chest radiograph remains
the gold standard to confirm central venous catheter tip position and rule out
associated lung complications like pneumothorax. We hypothesize that a
combination of transthoracic echocardiography and lung ultrasound is noninferior
to chest radiograph when used to accurately assess central venous catheter
positioning and screen for pneumothorax. SETTING: All operating rooms and
surgical and trauma ICUs at the institution. DESIGN: Single-center, prospective
noninferiority study. PATIENTS: Patients receiving ultrasound-guided subclavian
or internal jugular central venous catheters. INTERVENTIONS: During ultrasound
guided central venous catheter placement, correct positioning of central venous
catheter was accomplished by real-time visualization of the guide wire and
positive right atrial swirl sign using the subcostal four-chamber view. After
insertion, pneumothorax was ruled out by the presence of lung sliding and
seashore sign on M-mode. MEASUREMENTS AND MAIN RESULTS: Data analysis was done
for 137 patients. Chest radiograph ruled out pneumothorax in 137 of 137 patients
(100%). Lung ultrasound was performed in 123 of 137 patients and successfully
screened for pneumothorax in 123 of 123 (100%). Chest radiograph approximated
accurate catheter tip position in 136 of 137 patients (99.3%). Adequate subcostal
four-chamber views could not be obtained in 13 patients. Accurate positioning of
central venous catheter with ultrasound was then confirmed in 121 of 124 patients
(97.6%) as described previously. CONCLUSIONS: Transthoracic echocardiography and
lung ultrasound are noninferior to chest x-ray for screening of pneumothorax and
accurate central venous catheter positioning. Thus, the point of care use of
ultrasound can reduce central venous catheter insertion to use time, exposure to
radiation, and improve patient safety.
PMID- 28422779
TI - The Utility of High-Fidelity Simulation for Training Critical Care Fellows in the
Management of Extracorporeal Membrane Oxygenation Emergencies: A Randomized
Controlled Trial.
AB - OBJECTIVE: Although extracorporeal membrane oxygenation volume has increased,
proficiency in the technology requires extensive training. We compared
traditional water-drill-based extracorporeal membrane oxygenation training with
simulation-based extracorporeal membrane oxygenation training with the hypothesis
that simulation-based training is superior. DESIGN: Randomized controlled trial.
SETTING: Academic medical center. SUBJECTS: Pulmonary/critical care fellows.
INTERVENTIONS: Participants had a preintervention simulated extracorporeal
membrane oxygenation emergency (Sim1-recirculation) then randomized into
simulation and traditional groups. Each group participated in three teaching
scenarios, via high-fidelity simulation or via water-drills. After 6 weeks and
after 1 year, participants returned for two simulated extracorporeal membrane
oxygenation emergencies (Sim2-pump failure and Sim3-access insufficiency). Sim2
was a case encountered during teaching, whereas Sim3 was novel. A critical
action, necessary for resolution of each scenario, was preidentified for timing.
MEASUREMENTS AND MAIN RESULTS: Primary outcome was time required to perform
critical actions. Twenty-one fellows participated in the study (simulation, 10;
traditional, 11). Groups had similar scenario scores (p = 0.4) and times to
critical action (p = 0.8) on Sim1. At 6 weeks, both groups had similar scenario
scores on Sim2 (p = 0.5), but the simulation group scored higher on Sim3 (p =
0.03). Times to critical actions were shorter in the simulation group during Sim2
(127 vs 174 s, p = 0.004) and Sim3 (159 vs 300 s; p = 0.04). These findings
persisted at 1 year. CONCLUSIONS: In novice critical care fellows, simulation
based extracorporeal membrane oxygenation training is superior to traditional
training. Benefits transfer to novel scenarios and are maintained over the long
term. Further studies evaluating the utility of simulation in other learner
groups and for maintenance of proficiency are required.
PMID- 28422780
TI - Understanding the Gut Microbiota in Inflammatory and Functional Gastrointestinal
Diseases.
AB - OBJECTIVE: During the last decade, experimental and observational studies have
shown that patients with inflammatory bowel disease (IBD) and irritable bowel
syndrome (IBS) may have an altered intestinal microbial composition compared with
healthy individuals. However, no uniform microbial signature has as yet been
detected for either IBD or IBS. This review summarizes the current knowledge of
microbial dysbiosis and its potential relationship to the pathophysiology in IBD
and IBS. METHODS: A selective review was conducted to summarize the current
knowledge of gut microbiota in the pathophysiology of IBD and IBS. RESULTS:
Experimental and observational studies provide good evidence for intestinal
microbial dysbiosis in subgroups of IBD and IBS. Still, no uniform disease
pattern has been detected. This is most likely due to the heterogeneous nature of
IBD and IBS, in combination with the effects of intrinsic and extrinsic factors.
Such intrinsic factors include genetics, the gastrointestinal environment, and
the host immune system, whereas extrinsic factors include early life diet,
breastfeeding, and method of infant delivery. CONCLUSIONS: Recent and ongoing
work to define microbial dysbiosis in IBD and IBS shows promise, but future well
designed studies with well-characterized study individuals are needed. It is
likely that the microbial dysbiosis in IBD and IBS is dependent on the natural
disease course of IBD and symptom pattern in IBS. Therefore, assessment of the
entire microbiota along the gastrointestinal tract, in relationship to
confounding factors, symptom fluctuations, and other pathophysiological factors,
is needed for further understanding of the etiology of these common diseases.
PMID- 28422782
TI - Editorial introduction.
PMID- 28422783
TI - Lessons learned from humoral responses of HIV patients.
AB - PURPOSE OF REVIEW: Since 2009 many broadly neutralizing antibodies against HIV
have been identified, yet there is still no vaccine capable of inducing such
antibodies in humans. This review considers the early observations of HIV sera
neutralization in light of more recent studies and highlights areas for future
research. RECENT FINDINGS: Large clinical cohort studies using standardized
neutralization assays and pseudoviruses derived from primary isolates have shown
that 10-30% of HIV infections result in some level of serum neutralization
breadth. However, less than 10% of individuals develop a greater breadth of
neutralization and are termed elite neutralizers. SUMMARY: During HIV infection,
many individuals develop strain-specific neutralization against their viral
quasispecies, and similar immunogen-matched activity can now be induced in animal
models. However, only in a minority of infections do broadly neutralizing
antibodies develop. Therefore, understanding how the viral diversity, host immune
environment, and antibody repertoires intersect to support the generation of
neutralization breadth in elite neutralizers could provide guidelines as to how
to improve immunization responses.
PMID- 28422784
TI - B-cell abnormalities and impact on antibody response in HIV infection.
AB - PURPOSE OF REVIEW: The purpose of the present review is to provide an update on
the current development in the field of broadly neutralizing antibodies (bNabs)
and their potential use in the prevention and therapeutic settings, and an
evaluation of the B-cell abnormalities that may impair antibody responses in HIV
infection. RECENT FINDINGS: Major advances have been achieved in the
characterization of bNabs directed against different vulnerable regions of HIV
Envelope (Env). Recent observations have clearly demonstrated the ability of
bNabs to prevent HIV infection in the nonhuman primate model of HIV infection and
to suppress viremia in individuals with chronic HIV infection in the absence of
antiretroviral therapy. Furthermore, substantial advances have also been obtained
in the development of HIV Env proteins and immunization strategies inducing bNabs
in small animal models. Several studies have also shed light on the B-cell
abnormalities associated with the viremic phase of HIV infection that cause
impaired B-cell maturation and antibody responses. Of note, preliminary
observations have provided evidence for a correlation between the expansion of a
specific population of B cells, for example, germinal center B cells, the
expansion of T follicular helper cells (Tfh), and the generation of neutralizing
antibodies. SUMMARY: The recent observations on the antiviral effects of bNabs in
vivo indicate that bNabs may play a central role in both the prevention and the
therapeutic settings. The identification of the role of germinal center B cells
and Tfh cells as critical components of the immune response leading to the
generation of neutralizing antibodies, will allow the development of specific
immunization strategies for the stimulation of germinal center B cells and Tfh
cells. A lot of work still remains to be done for the delineation of B-cell and
Tfh cell biology from human lymphoid tissues and in the development of HIV Env
proteins and immunization strategies leading to the generation of bNabs.
PMID- 28422785
TI - Role of nonneutralizing antibodies in vaccines and/or HIV infected individuals.
AB - PURPOSE OF REVIEW: Increased body of evidence gathered over time indicate that
antibodies are capable of many inhibitory mechanisms, virus neutralization being
just one of them. Nonneutralizing antibodyactivities interfering with HIV
replication can also lead to a decrease in viral load and even in-vivo
protection. RECENT FINDINGS: It was previously believed that neutralizing
antibodies can achieve sterilizing protection mainly by using their
neutralization capacities against the infecting virus directly at the portal of
virus entry. Recent findings show that protection can be obtained by neutralizing
antibodiesat distal sites of virus challenge. In this case, foci of virus
infection that escaped from initial inhibition of virus are eliminated presumably
by additional nonneutralizing antibody activities. These data inexorably
strengthen the diverse functions of antibodies and broaden their role as
antiviral mediator. SUMMARY: The review summarizes the current knowledge and the
difficulties to encompass the numerous functions of antibodies. A complete
understanding of the various facets of antibody functions is required to
efficiently induce them via next-generation vaccine design.
PMID- 28422786
TI - Antibody-mediated immune exclusion of HIV.
AB - PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans
occur through mucosal contact, the induction of mucosal anti-HIV immune responses
has remained understudied. Here we summarize data demonstrating the powerful
protection that is achievable at mucosal frontlines through virus-specific
mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization
with different monoclonal antibody subclasses but identical epitope specificity
(the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1
(dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus
(SHIV) acquisition in rhesus macaques at a higher rate than dIgA2. Both dIgAs
neutralized the challenge SHIV equally well. Protection was linked to better
virion capture and inhibition of cell-free virus transcytosis by dIgA1.
Synergistic interactions at the mucosal level between the IgG1 and dIgA2 versions
of this monoclonal antibody yielded complete protection. Active vaccine
strategies designed to induce mucosal IgA and systemic/mucosal IgG have given
promising data. SUMMARY: This review seeks to highlight the importance of mucosal
IgAs in preventing virus acquisition. Passive immunization gave proof-of-concept
for immune exclusion by mucosally administered monoclonal dIgAs. Unanswered
questions remain regarding the interplay between mucosal IgA and other host
immune defenses, including their induction with active immunization.
PMID- 28422787
TI - How HIV-1 entry mechanism and broadly neutralizing antibodies guide structure
based vaccine design.
AB - PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies
(bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1
entry mechanism is guiding the structure-based design of vaccine immunogens and
immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected
donors has led to an unprecedented understanding of the sites of vulnerability
that these antibodies target on the HIV-1 envelope (Env) as well as of the
immunological pathways that these antibody lineages follow to develop broad and
potent neutralization. Sites of vulnerability, however, reside in the context of
diverse Env conformations required for HIV-1 entry, including a prefusion-closed
state, a single-CD4-bound intermediate, a three-CD4-bound intermediate, a
prehairpin intermediate and postfusion states, and it is not always clear which
structural state optimally presents a particular site of vulnerability in the
vaccine context. Furthermore, detailed knowledge of immunological pathways has
led to debate among vaccine developers as to how much of the natural antibody
developmental pathway immunogens should mimic, ranging from only the recognized
epitope to multiple antigens from the antibody-virus coevolution process.
SUMMARY: A plethora of information on bNAbs is guiding HIV-1-vaccine development.
We highlight consideration of the appropriate structural context from the HIV-1
entry mechanism and extraordinary progress with replicating template B-cell
ontogenies.
PMID- 28422789
TI - Antigp41 membrane proximal external region antibodies and the art of using the
membrane for neutralization.
AB - PURPOSE OF REVIEW: We summarize the latest research on the progress to understand
the neutralizing epitopes present within the membrane proximal external region
(MPER) of the HIV-1 fusion protein subunit gp41. RECENT FINDINGS: The HIV-1
fusion protein subunit gp41 contains a highly conserved sequence that is
essential for membrane fusion and targeted by broadly neutralizing antibodies
such as 2F5, 4E10, Z13e1, and 10E8. These antibodies recognize a linear gp41
epitope with high affinity, but require additional hydrophobic sequences present
in their heavy chain CDR3 for neutralization. Recent structural studies on mAbs
4E10 and 10E8 provide molecular details for specific interactions with lipids and
implicate part of the transmembrane region as the relevant 10E8 epitope. Although
many different approaches have been applied to engineer gp41 immunogens that can
induce broadly neutralizing antibodies directed toward MPER, only modest success
has yet been reported. SUMMARY: The new structural details on the complex gp41
lipidic epitope will spur new approaches to design gp41-MPER immunogens that
might induce broadly neutralizing antibody responses.
PMID- 28422790
TI - Particle-based delivery of the HIV envelope protein.
AB - PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of
suitable antigens that elicit broadly neutralizing antibody responses targeting
HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle
based carriers allows higher avidity interactions and is therefore expected to
efficiently engage B cells, thus leading to affinity maturation that results in
superior antibody responses characterized by improved breadth, potency, and
durability. This review summarizes current work that is evaluating diverse types
of such particulate carriers for Env delivery. RECENT FINDINGS: Various types of
particle scaffolds are being investigated, encompassing group-specific antigen
derived virus-like particles, bacteria-derived proteins that self-assemble into
symmetrical nanoparticles, as well as liposomes assembled from membrane
components and recombinantly produced Env isoforms. Env-derived antigens from
peptides over selected isolates to improved, stabilized next-generation designer
Envs have been attached to such carriers. Immunological evaluation in animal
models showed that these structures often elicit superior humoral immune
responses. SUMMARY: The findings reviewed here emphasize the potential of
particle-based delivery modalities to elicit better antibody responses. Together
with advances in Env antigen design, these approaches may synergistically act
together on the way to obtain vaccine candidates that potentially induce
protective immune responses against HIV.
PMID- 28422788
TI - Stabilized HIV-1 envelope glycoprotein trimers for vaccine use.
AB - PURPOSE OF REVIEW: To provide an update on the latest developments in the field
of HIV-1 antibody-based soluble envelope glycoprotein (Env) trimer design for
vaccine use. RECENT FINDINGS: The development of soluble native-like HIV-1 Env
trimer immunogens has moved the field of antibody-based vaccine design forward
dramatically over the past few years with refinement of various stabilizing
approaches. However, despite this progress, significant challenges remain.
Firstly, although trimers are relatively stable in solution, they nevertheless
sample different conformational states, some of which may be less relevant to
binding and induction of broadly neutralizing antibodies (bNAbs). Secondly, these
trimers expose unwanted immunodominant surfaces that may distract the adaptive
immune response from recognizing more immunorecessive but conserved
neutralization-relevant surfaces on the trimer. The availability of atomic
resolution structural information has allowed guided design of mutations that
have further stabilized trimers and allowed reduced exposure of unwanted
epitopes. Moreover, chemical cross-linking approaches that do not require
structural information have also contributed to trimer stabilization and
selection of particular conformational forms. However, current knowledge suggests
that strategies additional to trimer stabilization will be required to elicit
bNAb, including targeting naive B cell receptors with specific immunogens, and
guiding B cell lineages toward recognizing conserved surfaces on Env with high
affinity. SUMMARY: This review will give a perspective on these challenges, and
summarize current approaches to overcoming them with the aim of developing
immunogens to elicit bNAb responses in humans by active vaccination.
PMID- 28422791
TI - Intrastructural help: improving the HIV-1 envelope antibody response induced by
virus-like particle vaccines.
AB - PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy
of HIV vaccines is increasingly recognized. Although different types of vaccines
were shown to induce antibodies with different Fc-activities, there is no clear
strategy how to raise antibody responses with a desired pattern of Fc-effector
functions. Given the central role of T-helper cells in regulating the germinal
center reaction and the differentiation of B cells in an antigen-specific manner,
the review will discuss whether T-helper cells directed against non-HIV envelope
(Env) antigens could be harnessed to improve the HIV-Env antibody response.
RECENT FINDINGS: Comparing CD4 T-cell responses in HIV-infected individuals with
and without neutralizing antibody breadth suggests that robust Gag-specific CD4 T
cells may provide important T-cell help to Env-specific B cells. In a murine
model, GagPol-specific T-helper cells were shown to provide intrastructural help
for HIV-Env-specific antibody responses after immunization with a virus-like
particle vaccine. GagPol-specific T-helper cells imprinted the IgG subtype ratio
observed for Gag onto the HIV-Env antibody response and modulated the
glycosylation pattern of the HIV Env-specific antibodies. SUMMARY:
Intrastructural help is a promising strategy to improve overall levels and Fc
effector functions of the HIV-Env antibody response.
PMID- 28422792
TI - Progress in HIV-1 antibody research using humanized mice.
AB - PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing
antibodies provide new opportunities to successfully prevent, treat, and
potentially cure HIV-1 infection. To test their activity in vivo, humanized mice
have been shown to be a powerful model and were used to investigate antibody
mediated prevention and therapy approaches. In this review, we will summarize
recent findings in humanized mice that have informed on the potential use of
broadly neutralizing antibodies targeting HIV-1 in humans. RECENT FINDINGS:
Humanized mouse models have been used to demonstrate the antiviral efficacy of
HIV-1 neutralizing antibodies in vivo. It has been shown that a combination of
antibodies can suppress viremia below the limit of detection and targets the HIV
1 reservoir. Moreover, passively administered antibodies and vector-mediated
antibody production protect humanized mice from HIV-1 infection. Finally,
immunization studies in knock-in/transgenic mice carrying human antibody gene
segments have informed on potential vaccination strategies to induce broad and
potent HIV-1 neutralizing antibodies. SUMMARY: Humanized mouse models are of
great value for HIV-1 research. They represent a highly versatile in vivo system
to investigate novel approaches for HIV-1 prevention and therapy and expedite the
critical translation from basic findings to clinical application.
PMID- 28422794
TI - Intrathecal Morphine in Spine Surgery: A Meta-analysis of Randomized Controlled
Trials.
AB - STUDY DESIGN: Meta-analysis of randomized controlled trials (RCTs). OBJECTIVE:
The aim of this study was to evaluate the effectiveness of intrathecal morphine
(ITM) in reducing postoperative pain and opioid analgesic consumption following
spine surgery. SUMMARY OF BACKGROUND DATA: The use of ITM following adult spine
surgery is of particular interest because of the ease of access to the thecal sac
and the potential to provide adequate analgesia at low doses. However, previous
studies of ITM have been limited by small sample sizes and conflicting results.
METHODS: A comprehensive search of PubMed, Web of Science, Clinicaltrials.gov,
and the Cochrane Central Register of Controlled Trials for prospective RCTs was
performed by two independent reviewers. Postoperative opioid consumption, pain
scores, and complications were documented from the identified studies. Standard
mean differences (SMDs) were applied to continuous outcomes and odds ratios were
determined for dichotomous outcomes. RESULTS: Eight RCTs involving 393 subjects
met inclusion criteria and were included in this meta-analysis. Patients
receiving ITM (ITM group) as an adjunct to postoperative opioid analgesic were
compared to patients receiving postoperative opioids only (control group).
Postoperative morphine equivalent consumption was significantly lower during the
first 24 hours postoperative in the ITM group (P < 0.001). Pain scores were
similarly lower in the first 24 hours following spine surgery in those who
received ITM (P < 0.001). In patients administered ITM, a greater percentage
experienced pruritus (P < 0.001). Respiratory depression was solely encountered
in the ITM group (P = 0.25). There were no significant differences between the
ITM and control groups in terms of sedation (P = 0.18), nausea (P = 0.67),
vomiting (P = 0.62), or length of stay (P = 0.13). CONCLUSION: In patients
undergoing spine surgery, use of ITM significantly reduced opioid analgesic
consumption and Visual Analogue Schores pain scores compared to controls within
the first 24 hours postoperatively. High-quality, follow-up RCTs with large
sample sizes are recommended to determine the potential of supplementary ITM in
spine surgery and complete the side effects profile. LEVEL OF EVIDENCE: 1.
PMID- 28422795
TI - Trial Design and Endpoint Evaluation in Clinical Studies Addressing Chronic Back
Pain.
AB - STUDY DESIGN: A review of the literature evaluating clinical trials of chronic
back pain. OBJECTIVE: To assist physicians in assessing the quality of clinical
trial data to make the most informed treatment decisions. SUMMARY OF BACKGROUND
DATA: Chronic pain is a tremendous public health issue, affecting close to 100
million adults in the United States, and costs the American people billions of
dollars. One traditional treatment approach, the long-term use of opiate
medications, has recently come under intense scrutiny for problems with
complications, diversion, abuse, addiction, and lack of efficacy. In addition,
the Centers for Disease Control and Prevention has recognized that
overprescribing opiates has enabled an overdose crisis, and written guidelines
that are intended to limit their use. It is for this reason that physicians must
have a comprehensive understanding of the range of drug-free alternative
therapies available and have the tools needed to rigorously evaluate the chronic
pain literature so they can make appropriate treatment decisions. METHODS: An
evaluation of how clinical trials are designed and ranked, outcome measures, and
costs for a variety of therapies is necessary to determine which treatment option
is the most efficacious for an individual patient. RESULTS: Clinical trial data
demonstrate that spinal cord stimulation (SCS) is a safe and effective treatment
option for many types of chronic pain, including back pain. The last 10 years has
brought tremendous advances in the field of neuromodulation. Today, several
treatment modalities exist for SCS requiring the physician to be able to
critically evaluate and interpret the literature and determine which modality has
the strongest evidence. When evaluating clinical trial data of patients with
chronic back pain, emphasis must be placed on well designed, randomized
controlled trials with long-term follow-up producing level I evidence. These data
are obtained in a rigorous manner and are likely to have less bias when compared
with lower level studies. CONCLUSION: The level I studies performed to date have
provided evidence that treatment with SCS results in sustainable pain reduction
and improvements in scores measuring quality of life and patient functioning in
those patients with chronic intractable back pain. LEVEL OF EVIDENCE: 5.
PMID- 28422793
TI - Engineering antibody-like inhibitors to prevent and treat HIV-1 infection.
AB - PURPOSE OF REVIEW: Here we discuss recently developed HIV-1 entry inhibitors that
can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an
emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than
any single antibody characterized to date. We also discuss the use of recombinant
adeno-associated virus (rAAV) vectors as a platform for long-term expression of
these inhibitors. RECENT FINDINGS: Much of the exterior of HIV-1 Env can be
targeted by broadly neutralizing antibodies (bNAbs). Recent studies combine the
variable regions or Fabs from different bNAbs, often with the receptor-mimetic
components, to create broad, potent, and hard-to-escape inhibitors. rAAV vectors
can express these inhibitors for years in vivo, highlighting their ability to
prevent or treat HIV-1 infection. SUMMARY: By targeting multiple epitopes on Env,
bispecific and antibody-like inhibitors can be broader and more potent than
bNAbs. These inhibitors can provide long-term protection from, and perhaps
suppression of, HIV-1 if they are administered by a delivery platform, like rAAV
vectors, but only after rAAV limitations are addressed.
PMID- 28422796
TI - Waterless Hand Rub Versus Traditional Hand Scrub Methods for Preventing the
Surgical Site Infection in Orthopedic Surgery.
AB - : MINI: Fourteen hundred consecutive patients were investigated for evaluating
the utility of waterless hand rub before orthopaedic surgery. The risk in the
surgical site infection incidence was the same, but costs of liquids used for
hand hygiene were cheaper and the hand hygiene time was shorter for waterless
protocol, compared with traditional hand scrub. STUDY DESIGN: A retrospective
cohort study with prospectively collected data. OBJECTIVE: The aim of this study
was to compare SSI incidences, the cost of hand hygiene agents, and hand hygiene
time between the traditional hand scrub and the waterless hand rub protocols
before orthopedic surgery. SUMMARY OF BACKGROUND DATA: Surgical site infections
(SSI) prolong hospitalization and are a leading nosocomial cause of morbidity and
a source of excess cost. Recently, a waterless hand rub protocol comprising
alcohol based chlorhexidine gluconate for use before surgery was developed, but
no studies have yet examined its utility in orthopedic surgery. METHODS: Fourteen
hundred consecutive patients who underwent orthopedic surgery (spine, joint
replacement, hand, and trauma surgeries) in our hospital since April 1, 2012 were
included. A total of 712 cases underwent following traditional hand scrub between
April 1, 2012 and April 30, 2013 and 688 cases underwent following waterless hand
rub between June 1, 2013 and April 30, 2014. We compared SSI incidences within
all and each subcategory between two hand hygiene protocols. All patients were
screened for SSI within 1 year after surgery. We compared the cost of hand
hygiene agents and hand hygiene time between two groups. RESULTS: The SSI
incidences were 1.3% (9 of 712) following the traditional protocol (2 deep and 7
superficial infections) and 1.1% (8 of 688) following the waterless protocol (all
superficial infections). There were no significant differences between the two
groups. The costs of liquids used for one hand hygiene were about $2 for
traditional hand scrub and less than $1 for waterless hand rub. The mean hand
hygiene time was 264 seconds with the traditional protocol and 160 seconds with
the waterless protocol. CONCLUSION: Waterless hand rub with an alcohol based
chlorhexidine gluconate solution can be a safe, quick, and cost-effective
alternative to traditional hand scrub. LEVEL OF EVIDENCE: 3.
PMID- 28422798
TI - Anterior Versus Posterior Thoracic Discectomy: A Systematic Review.
AB - STUDY DESIGN: Systematic literature review. OBJECTIVE: The aim of this study was
to systematically review the current evidence in the literature on thoracic
discectomies, to compare the clinical outcomes, and to determine whether there is
evidence to support the use of either the anterior or posterior approach. SUMMARY
OF BACKGROUND DATA: Thoracic disc herniations (TDHs) often present with
myelopathy, radiculopathy, or a combination of both. The posterior approach for
thoracic discectomy has been associated with a lower complication rate, but no
systematic review exists comparing the clinical outcomes. METHODS: MEDLINE,
EMBASE, and The Cochrane Library databases were searched in accordance with the
PRISMA guidelines for studies performing an anterior or posterior thoracic
discectomy. The methodological quality was assessed using the Methodological
Index for Non-Randomized Studies checklist. The reported clinical outcomes were
evaluated using risk ratio, with a P < 0.05 being considered statistically
significant. RESULTS: Thirty-seven clinical studies with 1156 patients with 1300
TDHs were included in this review. There was no statistically significant
difference in the total neurological improvement or neurological worsening using
either an anterior approach or a posterior approach (P = 0.02812 and P = 0.5232,
respectively). However, there was a statistically significant higher rate of
total complications in the anterior approach (P = 0.0024). CONCLUSION: The
anterior approach and posterior approach have been shown to be very similar in
terms of neurological outcomes. Although the posterior approach was shown to have
a lower rate of total complications, this was largely because of a decrease in
minor respiratory complications seen in the anterior approach. The optimal
approach may therefore be based on surgeon preference as well as patient factors,
specifically cardiorespiratory with American Society of Anaesthesiologists
grading. LEVEL OF EVIDENCE: 4.
PMID- 28422799
TI - Publication Rates of Abstracts Accepted to the 2010-2012 Annual Meetings of the
North American Spine Society.
AB - : MINI: The publication rate of conference abstract presentations as full-length
manuscripts is a potential measure of meeting quality. 43.8% of abstracts
presented at the 2010-2012 North American Spine Society annual meetings were
published as full-length manuscripts within 3 years. Podium presentations and
"Best" or "Outstanding" paper presentations were more likely to be published.
STUDY DESIGN: Retrospective review of conference abstracts. OBJECTIVE: The aim of
this study was to determine the publication rate of podium and poster
presentations at the 2010-2012 North American Spine Society (NASS) annual
meetings. SUMMARY OF BACKGROUND DATA: Presentations at medical conferences are
utilized to disseminate new clinical information. The orthopedic literature
estimates the rate of publication for abstracts presented at major meetings to be
between 34.0% and 67.1%. However, few studies have analyzed the publication rate
of accepted abstracts to the NASS annual meetings. METHODS: All abstracts
presented at the 2010-2012 NASS annual meetings were reviewed. PubMed and Google
Scholar databases were searched to determine whether each abstract was published
as a full-length manuscript before or up to 3 years after its NASS meeting
presentation. Statistical analyses included descriptive statistics, Poisson
regression with robust error variance, and linear regression. RESULTS: A total of
1045 abstracts were accepted to the 2010-2012 NASS annual meetings. 43.8% were
published before or up to 3 years after their NASS presentation. Podium
presentations were more likely to be published than poster presentations (47.1%
vs. 37.7%, P = 0.005). Abstracts with "Best" or "Outstanding" designations were
also more likely to be published than abstracts without those designations (54.4%
vs. 45.0%, P = 0.034). Presentations designated as "Best" or "Outstanding"
articles had shorter time to publication than presentations without those
designations (369 vs. 486 days, P = 0.002). CONCLUSION: This study suggests that
only 43.8% of abstracts accepted to NASS are published as full-length
manuscripts. As such, practitioners should use caution when altering clinical
practice based solely on conference presentations. Additionally, podium
presentations are more likely to be published than poster presentations. This
trend may be reflective of the higher quality of abstracts accepted as podiums,
or may be associated with a larger number of lower-quality abstracts being
accepted because of the use of the e-poster format. LEVEL OF EVIDENCE: 4.
PMID- 28422800
TI - Evaluation of Water Content in Lumbar Intervertebral Discs and Facet Joints
Before and After Physiological Loading Using T2 Mapping MRI.
AB - STUDY DESIGN: T2 mapping was used to quantify the water content of lumbar spine
intervertebral discs (IVDs) and facet joints before and after physiological
loading. OBJECTIVE: The aim of this study was to clarify the interaction between
lumbar spine IVD and facet joints as load-bearing structures by measuring the
water content of their matrix after physiological loading using T2 mapping
magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: To date, few
reports have functionally evaluated lumbar spine IVD and facet joints, and their
interaction in vivo. T2 mapping may help detect changes in the water content of
IVD and articular cartilage of facet joints before and after physiological
loading, thereby enabling the evaluation of changes in interacted water retention
between IVD and facet joints. METHODS: Twenty asymptomatic volunteers (10 female
and 10 male volunteers; mean age, 19.3 years; age range, 19-20 years) underwent
MRI before and after physiological loading such as lumbar flexion, extension, and
rotation. Each IVD from L1/2 to L5/S1 was sliced at center of the disc space, and
the T2 value was measured at the nucleus pulposus (NP), anterior annulus fibrosus
(AF), posterior AF, and bilateral facet joints. RESULTS: In the NP, T2 values
significantly decreased after exercise at every lumbar spinal level. In the
anterior AF, there were no significant differences in T2 values at any level. In
the posterior AF, T2 values significantly increased only at L4/5. In the
bilateral facet joints, T2 values significantly decreased after exercise at every
level. CONCLUSION: There was a significant decrease in the water content of facet
joints and the NP at every lumbar spinal level after dynamic loading by physical
lumbar exercise. These changes appear to play an important and interactional role
in the maintenance of the interstitial matrix in the IVD NP and cartilage in the
facet joint. LEVEL OF EVIDENCE: 3.
PMID- 28422801
TI - Interrater and Test-Retest Reliability of the Beery Visual-Motor Integration in
Schoolchildren.
AB - PURPOSE: To assess interrater and test-retest reliability of the 6th Edition
Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) and test
retest reliability of the VMI Visual Perception Supplemental Test (VMIp) in
school-age children. METHODS: Subjects were 163 Native American third- to eighth
grade students with no significant refractive error (astigmatism <1.00 D, myopia
<0.75 D, hyperopia <2.50 D, anisometropia <1.50 D) or ocular abnormalities. The
VMI and VMIp were administered twice, on separate days. All VMI tests were scored
by two trained scorers, and a subset of 50 tests was also scored by an
experienced scorer. Scorers strictly applied objective scoring criteria. Analyses
included interrater and test-retest assessments of bias, 95% limits of agreement,
and intraclass correlation analysis. RESULTS: Trained scorers had no significant
scoring bias compared with the experienced scorer. One of the two trained scorers
tended to provide higher scores than the other (mean difference in standardized
scores = 1.54). Interrater correlations were strong (0.75 to 0.88). VMI and VMIp
test-retest comparisons indicated no significant bias (subjects did not tend to
score better on retest). Test-retest correlations were moderate (0.54 to 0.58).
The 95% limits of agreement for the VMI were -24.14 to 24.67 (scorer 1) and
26.06 to 26.58 (scorer 2), and the 95% limits of agreement for the VMIp were
27.11 to 27.34. CONCLUSIONS: The 95% limit of agreement for test-retest
differences will be useful for determining if the VMI and VMIp have sufficient
sensitivity for detecting change with treatment in both clinical and research
settings. Further research on test-retest reliability reporting 95% limits of
agreement for children across different age ranges is recommended, particularly
if the test is to be used to detect changes due to intervention or treatment.
PMID- 28422802
TI - Validity and Repeatability of a Novel Dynamic Visual Acuity System.
AB - PURPOSE: In many sports, athletes rely on visual information from the environment
to perform. Some literature suggests athletes have superior visual abilities to
non-athletes, particularly on tasks representative of the visual demands of their
sport, such as dynamic acuity, eye movement accuracy and speed, and peripheral
vision. Other literature suggests there is no difference between athletes and non
athletes, at least when standard clinical assessments are employed. A limitation
of the literature is that almost none of the research has been conducted with
standardized, validated tools. This is partly caused by a lack of readily
available tools to measure tasks representative of the visual demands of sport,
and available tests have typically not been validated against current clinical
standards. The purpose of this study is to examine the validity and repeatability
of a novel visual acuity system (moV&; V&MP Vision Suite) recently developed in
the Vision & Motor Performance Lab (V&MP). moV& permits the measurement of many
visual function parameters including dynamic visual acuity with predictable,
random, and jittering target motion. METHODS: Twenty-five participants attended
two study visits, separated by a minimum of 2 weeks. At each visit, static and
dynamic visual acuity was measured using Snellen, ETDRS, and moV& charts. Static
visual acuities were compared to determine the validity of moV&, and both static
and dynamic visual acuities were compared between visits to determine the test
retest repeatability. RESULTS: moV& static visual acuities are clinically similar
to visual acuities measured with the ETDRS chart (moV&, -0.09 +/- 0.13; ETDRS,
0.03 +/- 0.11, concordance correlation coefficient 0.726). Additionally, all
static, dynamic, and jitter visual acuities demonstrate good test-retest
repeatability (Lin's concordance correlation coefficient range 0.451-0.953).
CONCLUSIONS: moV& provides good clinical measures of static visual acuity that
are comparable to both Snellen and ETDRS measures. Dynamic visual acuity measures
demonstrate good test-retest repeatability.
PMID- 28422803
TI - Marijuana Use and Self-reported Quality of Eyesight.
AB - PURPOSE: There is increasing use of marijuana among young adults and more states
in the United States are legalizing medical marijuana use. A number of studies
have revealed both the beneficial and harmful effects of marijuana to the human
system. Despite some beneficial effects, studies have shown marijuana to have a
lot of deleterious effects on the visual system, which subsequently reduces the
quality of eyesight. The aim of this study was to investigate if heavy marijuana
smoking is associated with a poor quality of eyesight compared with light/no use
of marijuana. METHODS: The National Longitudinal Survey of Youths (NLSY79), a
nationally representative sample of 12,686 young men and women surveyed in 1979
to 2010 was used for this study. The quality of eyesight of 1304 heavy marijuana
users was compared with 1304 respondents with light or no marijuana use. The t
test, multivariate and weighted logistic regression were used in the data
analysis. RESULTS: There was no statistically significant difference in the self
reported quality of eyesight among heavy marijuana smokers compared with youths
who never used marijuana or are light marijuana users. Among heavy marijuana
smokers, males and high school graduates have decreased odds of reporting a poor
quality of eyesight, whereas blacks have increased odds of reporting a poor
quality of eyesight. CONCLUSIONS: The self-reported quality of eyesight among
marijuana users can aid clinicians and other health practitioners facilitate the
development of sex-, racial/ethnic-, and educational level-informed prevention
and early intervention programs and also help characterize public opinions
regarding cannabis, which are particularly relevant given the ongoing debate
concerning the medicalization and legalization of cannabis in the United States.
PMID- 28422804
TI - A Review of Ocular Graft-Versus-Host Disease.
AB - : Graft-versus-host disease (GVHD) is a major complication that occurs following
allogeneic hematopoietic stem cell transplantation, which is a potential curative
therapy used in a variety of malignant or benign hematological diseases. Graft
versus-host disease primarily occurs in many organs, but most notably in the
skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal
system. Ocular manifestations of GVHD may precede other systemic GVHD findings,
and it may be a poor prognosis for mortality. While all parts of the eye may be
affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or
keratoconjunctivitis sicca is the most common presenting manifestation of chronic
ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which
involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to
tear film deficiency and instability. Depending on the severity of ocular
involvement and response to treatment, ocular GVHD may cause decreased quality of
life. Management of GVHD begins with prevention by understanding risk factors and
by implementing prophylactic treatment after allogeneic hematopoietic stem cell
transplantation. A multidisciplinary approach to the prevention and treatment of
GVHD is important, and there are currently no preventive therapies available for
ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular
surface lubrication and support, tear film stabilization, inflammation reduction,
and surgical intervention. The goal of this review is to define ocular GVHD and
its categorical manifestations, as well as to describe the importance of
comprehensive assessment, diagnosis, and ophthalmologic treatment and management
of ocular GVHD with a multidisciplinary approach.
PMID- 28422805
TI - A Randomized Pilot Study Comparing Ketamine and Methohexital Anesthesia for
Electroconvulsive Therapy in Patients With Depression.
AB - OBJECTIVE: This randomized controlled pilot study examines the differences in
response to electroconvulsive therapy (ECT) as defined by an improvement of
depressive symptoms between ketamine and methohexital as the primary anesthetic
agent. Adverse effects and cognitive tolerability were also examined. METHODS:
Subjects undergoing ECT for unipolar or bipolar depression were randomized to
receive ketamine or methohexital as the anesthetic agent. Primary outcome measure
includes the Hamilton rating scale for depression (17-item). Secondary outcome
measures included the mini-mental status examination and Beck depression
inventory. All ratings were conducted masked to anesthetic agent. Because of
multiple outcome measures obtained over time, mixed models were used to account
for the correlations among the measurements within the subjects. Because outcomes
were either normally distributed or approximately normally distributed, general
linear mixed models were fit with a random intercept specified. RESULTS: A total
of 21 subjects were enrolled, and 16 were randomized (methohexital, n = 8;
ketamine, n = 8). The 2 treatment groups did not differ statistically in any
demographic characteristic. No statistical difference was found between the
ketamine and methohexital groups for an improvement in depressive symptoms (P =
0.6); however, subjects in both groups showed significant improvement in
depression over time (ketamine, P < 0.0001; methohexital, P < 0.0001). Mini
mental status examination results did not differ between groups, and fatigue was
reported more in subjects receiving ketamine (P = 0.03). CONCLUSIONS: The results
of this pilot study are inconclusive because they lack power to support an
advantage of ketamine anesthesia compared with methohexital in ameliorating
depressive symptoms for electroconvulsive therapy.
PMID- 28422806
TI - Improvement of Image Quality in Unenhanced Dual-Layer CT of the Head Using
Virtual Monoenergetic Images Compared With Polyenergetic Single-Energy CT.
AB - OBJECTIVES: The aims of this study were to compare virtual monoenergetic images
and polyenergetic images reconstructed from unenhanced dual-layer detector
computed tomography (DLCT) of the head and to determine kiloelectron volt levels
that optimize image quality, particularly the gray-white matter contrast, and
reduce beam hardening artifacts caused by the skull. MATERIALS AND METHODS:
Institutional review board approval was obtained. Forty patients that received
DLCT were included in this retrospective study; of these patients, 22 were women
and 18 were men. The average age was 61.5 +/- 14.3 years. Virtual monoenergetic
images were reconstructed from spectral base images at 40 keV to 120 keV. To
calculate signal-to-noise ratio and contrast-to-noise ratio, attenuation and
standard deviation of supratentorial gray and white matter were measured in
virtual monoenergetic and polyenergetic images. Beam hardening artifacts were
detected close to the calvarium and in the posterior fossa. Two radiologists
rated the assessment of gray-white matter differentiation and of the subcalvarial
space, as well as the artifacts caused by the skull and image noise. Student t
test and Wilcoxon test were used to determine significance. RESULTS: Compared
with polyenergetic images, superior signal-to-noise ratio and superior contrast
to-noise ratio of gray and white matter were observed in virtual monoenergetic
images at low kiloelectron volt levels (P < 0.0001). Subcalvarial artifacts were
significantly lower at 120 keV (P < 0.02). Artifacts measured in the posterior
fossa were generally lower at high kiloelectron volt levels; however, no
statistical significance was detected. Virtual monoenergetic images were rated
superior to polyenergetic images in regard to all 4 criteria (P < 0.0001). The
observers reported an optimal radiological assessment of gray-white matter
differentiation at 65 keV and optimal assessment of subcalvarial space at 120
keV. CONCLUSIONS: In comparison to polyenergetic images, virtual monoenergetic
images reconstructed from unenhanced DLCT of the head at 65 keV and 120 keV allow
to optimize gray-white matter contrast and reduce beam hardening artifacts caused
by the skull, respectively.
PMID- 28422807
TI - Clinical Robustness of Accelerated and Optimized Abdominal Diffusion-Weighted
Imaging.
AB - OBJECTIVES: The aim of this study was to assess the robustness of an accelerated
and optimized diffusion-weighted sequence in clinical routine abdominal imaging
using the simultaneous multislice (SMS) technique for scan time reduction and 3
dimensional (3D) diagonal diffusion mode to optimize image quality. MATERIALS AND
METHODS: One hundred fifty consecutive patients received clinically indicated
magnetic resonance imaging for abdominal imaging including an optimized SMS
diffusion-weighted sequence (DWIOPT: diffusion mode 3D diagonal; SMS factor 2;
scan time 1:44 minutes). A subgroup of 41 patients additionally received a
standard diffusion-weighted sequence as reference (DWISTD: diffusion mode 4-scan
trace; scan time 2:35 minutes). Qualitative and quantitative image parameters of
DWISTD and DWIOPT were assessed and compared interindividually within the
subgroup using dedicated statistics. RESULTS: In all patients, image quality
ratings in DWIOPT were rated very high (overall image quality, 4.6 [4-5]; contour
sharpness of right/left hepatic lobe, 4.6 [4-5]/4.4 [4-5]; and lesion
conspicuity, 4.5 [4.5-5]). Interindividually, DWIOPT proved superior to DWISTD in
comparison of overall image quality (4.6 [4.6-4.7] vs 4.2 [4.1-4.2]; P = 0.025)
and contour sharpness of the right/left hepatic lobe (4.6 [4.5-4.7]/4.3 [4.0-4.3]
vs 4.3 [4.1-43]/4.0[3.0-4.0]; each P = 0.045); lesion conspicuity was comparable
in DWIOPT and DWISTD (4.0 [4.8-5] vs 4.4 [4-5]; P = 0.461), and apparent
diffusion coefficient (ADC) values showed no statistically significant difference
(ADCOPT vs ADCSTD: right hepatic lobe, P = 0.084; kidney, P = 0.445). Interreader
agreement was substantial with a kappa value of 0.78 (P < 0.001). CONCLUSIONS:
Diffusion-weighted imaging of the abdomen can be considerably accelerated and
optimized integrating the SMS technique and a 3D diagonal diffusion mode. In a
large patient cohort, this approach proved of superior image quality while
maintaining similar ADC values compared with standard DWI. This technique seems
applicable for daily clinical routine.
PMID- 28422808
TI - Diagnosis of Chronic Intestinal Pseudo-obstruction and Megacystis by Sequencing
the ACTG2 Gene.
AB - OBJECTIVES: The diagnosis of chronic intestinal pseudo-obstruction has depended
on clinical features, manometry, and imaging. This report aimed to determine the
efficacy of sequencing the actin gamma-2 (ACTG2) gene for diagnosis. In addition,
the goal was to determine how often a mutation would be found in our randomly
collected cohort of probands and those probands published previously. METHODS:
Whole exome sequencing was performed in 4 probands with chronic intestinal pseudo
obstruction. Subsequently, only the ACTG2 gene was sequenced in another 24
probands (total 28). We analyzed published data of 83 probands and our 28 (total
111) and determined how many had pathogenic variants and the precise genotype.
RESULTS: Whole exome and Sanger sequencing revealed a pathogenic variant in the
ACTG2 gene in 4 out of 28 of our probands and in 45 out of 83 published probands
(49/111 [44.1%]). Moreover, a mutational hotspot in the ACTG2 gene was
recognized. Genetic heterogeneity is evident. CONCLUSIONS: Pooled gene sequencing
results from 1 individual in each of 111 families enabled a precise diagnosis of
an ACTG2 mutation in 49 (44%). The benefit to patients and families of early
confirmation of a motility disorder not only helps avoid unnecessary
intervention, but also enables institution of appropriate treatments and
avoidance of secondary disorders such as malnutrition and poor growth. Knowledge
of a pathogenic variant in a parent, with a 50% risk of recurrence, provides an
opportunity for genetic counseling.
PMID- 28422809
TI - Associations Between Dietary Intake Before 6 Months of Age and Rapid Weight Gain
Among HIV-exposed Uninfected Infants.
AB - INTRODUCTION: HIV-exposed, uninfected (HEU) infants are potentially at risk for
cardiovascular disease due to in utero exposures. Feeding practices of the infant
could compound this risk. Few studies have, however, evaluated dietary intake of
HEU infants. We determined dietary factors associated with rapid weight gain
(RWG) among HEU infants from birth to 6 months followed at the University of
Miami HIV Screening Program. METHODS: In this cross-sectional analysis, logistic
regression was used to determine dietary factors associated with RWG defined as a
>0.67 SD change in weight-for-age z score from birth to assessment (0.3-6
months). Other covariates included demographics, birth, maternal and gestational
characteristics, and antiretroviral exposures. RESULTS: A total of 86 full-term
HEU infants with a mean age of 3.4 months (SD 1.8 months) were included in this
analysis. Fifty-five percent of mothers were obese. Overall, 39.5% of infants
exhibited RWG. A significant association between consumption of infant cereal and
RWG (odds ratio, 3.52; 95% confidence interval, 1.02-12.10) was found after
adjusting for birth weight, current age, and energy intake. Those infants who
consumed the highest tertile of protein were less likely to gain weight rapidly
after adjusting for the same covariates (odds ratio, 0.15; 95% confidence
interval, 0.02-0.94). CONCLUSIONS: Overall differences in weight gain during
early infancy are at least partly explained by means of infant feeding in young
HEU infants in the United States. Dietary counseling for families of HEU should
reinforce current feeding practice recommendations of the American Academy of
Pediatrics.
PMID- 28422812
TI - Randomized Double-blind Trial of Ringer Lactate Versus Normal Saline in Pediatric
Acute Severe Diarrheal Dehydration.
AB - OBJECTIVE: The aim of this study was to compare the effectiveness of Ringer
lactate (RL) versus normal saline (NS) in the correction of pediatric acute
severe diarrheal dehydration, as measured by improvement in clinical status and
pH (>=7.35). METHODS: A total of 68 children ages 1 month to 12 years with acute
severe diarrheal dehydration (World Health Organization [WHO] classification)
were randomized into RL (n = 34) and NS groups (n = 34) and received 100 mL/kg of
the assigned intravenous fluid according to WHO PLAN-C for the management of
diarrheal dehydration. The primary outcome was an improvement in clinical status
and pH (>=7.35) at the end of 6 hours. Secondary outcomes were changes in serum
electrolytes, renal and blood gas parameters, the volume of fluid required for
dehydration correction excluding the first cycle, time to start oral feeding,
hospital stay, and cost-effectiveness analysis. RESULTS: Primary outcome was
achieved in 38% versus 23% (relative risk = 1.63, 95% confidence interval 0.80
3.40) in RL and NS groups, respectively. No significant differences were observed
in secondary outcomes in electrolytes, renal, and blood gas parameters. None
required second cycle of dehydration correction. Median (interquartile range)
time to start oral feeding (1.0 [0.19-2.0] vs 1.5 [0.5-2.0] hours) and hospital
stay (2.0 [1.0-2.0] vs 2.0 [2.0-2.0] days) was similar. The median total cost was
higher in RL than NS group ((Equation is included in full-text article.)120
[(Equation is included in full-text article.)120-(Equation is included in full
text article.)180] vs (Equation is included in full-text article.)55 [(Equation
is included in full-text article.)55-(Equation is included in full-text
article.)82], P <= 0.001). CONCLUSION: In pediatric acute severe diarrheal
dehydration, resuscitation with RL and NS was associated with similar clinical
improvement and biochemical resolution. Hence, NS is to be considered as the
fluid of choice because of the clinical improvement, cost, and availability.
PMID- 28422813
TI - New Approach in Assessing Core Muscle Endurance Using Ratings of Perceived
Exertion.
AB - George, JD, Tolley, JR, Vehrs, PR, Reece, JD, Akay, MF, and Cambridge, EDJ. New
approach in assessing core muscle endurance using ratings of perceived exertion.
J Strength Cond Res 32(4): 1081-1088, 2018-This study sought to develop
regression models to estimate maximal endurance time using data from 4 core
muscle endurance tests. Eighty healthy university students (age: 22.7 +/- 1.9
years) performed the plank, right side-bridge, left side-bridge, and back
extension tests in a random order. Participants were instructed to hold each
static position for a maximal endurance time, while maintaining proper form, and
then rest for 5 minutes between tests. A test administrator recorded
participants' ratings of perceived exertion (RPE; a modified 10-point scale)
every 5 seconds. Based on regression analysis, the elapsed time to reach an RPE
of 8 (RPE8) exhibited statistical significance (p < 0.0001) and the highest
accuracy as compared with lower RPE values. The following univariate regression
models were generated to estimate maximal endurance time across the 4 tests:
plank (r = 0.94; standard error of estimate [SEE] = 17.6 seconds; n = 77) = 23.9
+ (1.110 * RPE8); right side-bridge (r = 0.92; SEE = 11.4 seconds; n = 80) = 18.5
+ (1.022 * RPE8); left side-bridge (r = 0.93; SEE = 10.8 seconds; n = 80) = 16.8
+ (1.062 * RPE8); and back extension (r = 0.93; SEE = 14.2 seconds; n = 79) =
21.5 + (1.027 * RPE8). These results suggest that submaximal protocols based on
elapsed time to reach RPE8 provide strength and conditioning professionals
relatively accurate univariate regression equation estimates of maximal core
muscle endurance time and offer a viable submaximal alternative to maximal
capacity testing when time efficiency, participant safety, or certain educational
objectives may be a priority.
PMID- 28422814
TI - The Effect of Rubric-Guided, Focused, Personalized Coaching Sessions and Video
Recorded Presentations on Teaching Skills Among Fourth-Year Medical Students: A
Pilot Study.
AB - PROBLEM: As medical students become residents, teaching becomes an expected and
integral responsibility. Yet, training-for-teaching opportunities are lacking. In
2014, the authors designed a pilot study using rubric-guided, focused,
personalized coaching sessions and video-recorded presentations to improve
student teaching skills among fourth-year students at Harvard Medical School.
APPROACH: In 2014-2015, the authors recruited students from an elective on how to
tutor preclinical students for the pilot, which consisted of four phases: a
precoaching teaching presentation, a 30- to 45-minute coaching session, a
postcoaching teaching presentation, and blinded reviewer ratings. Students' pre-
and postcoaching presentations were video recorded. Using a scoring rubric for 15
teaching skills, students rated their pre- and postcoaching videos. Blinded
reviewers also rated the pre- and postcoaching presentations using the same
rubric with an additional category to gauge their overall impression. OUTCOMES:
Fourteen students completed all four phases of the pilot. Students' ratings
demonstrated statistically significant improvement in several teaching skills,
including presentation content (P < .001), rate of speech (P = .001), and opening
statement and learning objectives (P = .004). Blinded reviewers' ratings
demonstrated statistically significant improvements in several teaching skills,
including opening statement and learning objectives (P < .001), overall
impression (P = .001), and conclusion and summary of learning objectives (P =
.004). Students provided largely positive comments on the interventions. NEXT
STEPS: The authors will work toward addressing limitations in the rubric, using
coaching in different teaching settings, addressing the interventions'
generalizability, training coaches, and performing additional evaluations.
PMID- 28422815
TI - No Time for Silence: An Urgent Need for Political Activism Among the Medical
Community.
AB - Despite being a major stakeholder in the U.S. health care system, the medical
community has remained relatively mute in the debate over the future of the
Patient Protection and Affordable Care Act (ACA). If the ACA were repealed, tens
of millions of Americans would be in danger of losing their insurance, resulting
in a significant increase in mortality. Because misinformation about the ACA is
rampant, it is imperative that health care providers explain to the public what
exactly the ACA is and how repeal will affect patients. Traditionally, many in
the medical community have abstained from political advocacy for multiple
reasons, including compromising the doctor-patient relationship, financial
incentives, lack of experience with activism due to an absence of training in
that area, and fear of political retaliation. Encouragingly, there are
indications that the medical community is beginning to become more vocal. Medical
students are one example, having formed a grassroots response to repeal. However,
students need more guidance and support from experienced mentors to most
effectively serve as patient advocates. This is no time for silence: On this life
or-death issue, the medical community cannot afford to remain mute.
PMID- 28422816
TI - Why Not Wait? Eight Institutions Share Their Experiences Moving United States
Medical Licensing Examination Step 1 After Core Clinical Clerkships.
AB - The majority of medical students complete the United States Medical Licensing
Examination Step 1 after their foundational sciences; however, there are
compelling reasons to examine this practice. This article provides the
perspectives of eight MD-granting medical schools that have moved Step 1 after
the core clerkships, describing their rationale, logistics of the change,
outcomes, and lessons learned. The primary reasons these institutions cite for
moving Step 1 after clerkships are to foster more enduring and integrated basic
science learning connected to clinical care and to better prepare students for
the increasingly clinical focus of Step 1. Each school provides key features of
the preclerkship and clinical curricula and details concerning taking Steps 1 and
2, to allow other schools contemplating change to understand the landscape. Most
schools report an increase in aggregate Step 1 scores after the change. Despite
early positive outcomes, there may be unintended consequences to later scheduling
of Step 1, including relatively late student reevaluations of their career choice
if Step 1 scores are not competitive in the specialty area of their choice. The
score increases should be interpreted with caution: These schools may not be
representative with regard to mean Step 1 scores and failure rates. Other aspects
of curricular transformation and rising national Step 1 scores confound the data.
Although the optimal timing of Step 1 has yet to be determined, this article
summarizes the perspectives of eight schools that changed Step 1 timing, filling
a gap in the literature on this important topic.
PMID- 28422817
TI - Incidence and Implications of Left Ventricular Distention During Venoarterial
Extracorporeal Membrane Oxygenation Support.
AB - Left ventricular distention (LVD) during venoarterial extracorporeal membrane
oxygenation (VA-ECMO) support is increasingly recognized but seldom reported in
the literature. The current study defined LVD as not present (LVD-); subclinical
(LVD+, evidence of pulmonary edema on chest radiograph AND pulmonary artery
diastolic blood pressure greater than 25 mm Hg within the first 2 hours of
intensive care unit admission); or clinical (LVD++, need for decompression of the
left ventricle immediately following VA-ECMO initiation). Among 226 VA-ECMO
device runs, 121 had sufficient data to define LVD retrospectively. Nine patients
(7%) developed LVD++ requiring immediate decompression, and 27 patients (22%) met
the definition of LVD+. Survival to discharge was similar among groups (LVD++:
44%, LVD+: 41%, LVD-: 44%). However, myocardial recovery appeared inversely
related to the degree of LVD (LVD++: 11%, LVD+: 26%, LVD-: 40%). When death or
transition to device was considered as a composite outcome, event-free survival
was diminished in LVD++ and LVD+ patients compared with LVD-. Multivariable
analysis identified cannulation of VA-ECMO during extracorporeal cardiopulmonary
resuscitation (ECPR) as a risk factor for decompression (odds ratio [OR]: 3.64,
confidence interval [CI]: 1.21-10.98; p = 0.022). Using a novel definition of
LVD, the severity LVD was inversely related to the likelihood of myocardial
recovery. Survival did not differ between groups. Extracorporeal cardiopulmonary
resuscitation was associated with need for mechanical intervention.
PMID- 28422818
TI - Inhibition of Metabotropic Glutamate Receptor Subtype 1 Alters the Excitability
of the Commissural Pyramidal Neuron in the Rat Anterior Cingulate Cortex after
Chronic Constriction Injury to the Sciatic Nerve.
AB - BACKGROUND: Inhibition of the metabotropic glutamate receptor subtype 1 in the
anterior cingulate cortex has an analgesic effect during sustained nociceptive
hypersensitivity. However, the specific changes in different subtypes of anterior
cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of
metabotropic glutamate receptor subtype 1 inhibition on different neuronal
subtypes, have not been well studied. METHODS: Retrograde labeling combined with
immunofluorescence, whole cell clamp recording, and behavioral tests combined
with RNA interference were performed in a rat model of chronic constriction
injury to the sciatic nerve. RESULTS: Commissural layer 5 pyramidal neurons
(projecting to the contralateral cortex) existed in the anterior cingulate
cortex. The voltage-gated potassium channel subunit 2-mediated current in these
neurons were substantially reduced after chronic constriction injury (current
densities at +30 mV for the sham, and chronic constriction injury neurons were
[mean +/- SD] 10.22 +/- 3.42 pA/pF vs. 5.58 +/- 2.71 pA/pF, respectively; n = 11;
P < 0.01), which increased the spike width and fast afterhyperpolarization
potential, resulting in hyperexcitability. Inhibition of metabotropic glutamate
receptor subtype 1 alleviated the down-regulation of voltage-gated potassium
channel subunit 2 currents (current density increased by 8.11 +/- 3.22 pA/pF; n =
7; P < 0.01). Furthermore, knockdown of voltage-gated potassium channel subunit 2
current in the commissural neurons attenuated the analgesic effect of
metabotropic glutamate receptor subtype 1 inhibition (n = 6 rats; P < 0.05).
CONCLUSIONS: The effect of metabotropic glutamate receptor subtype 1 inhibition
on commissural anterior cingulate cortex layer 5 pyramidal neurons is likely
different with the modification of previously studied hyperpolarization
activated/cyclic nucleotide-gated channel-dependent neurons but relies on the
alteration of voltage-gated potassium channel subunit 2 currents. These results
will contribute to a better understanding of the therapeutic role of metabotropic
glutamate receptor subtype 1 in chronic pain.
PMID- 28422819
TI - GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression,
Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery.
AB - BACKGROUND: Angiotensin II receptor type 1-mediated activation of the alpha
subunit of the heterotrimeric Gq protein evokes increased vasoconstriction and
may promote hypertrophy-induced myocardial damage. The authors recently
identified a TT(-695/-694)GC polymorphism in the human Gq promoter, the GC allele
being associated with an increased prevalence of cardiac hypertrophy. In this
article, the authors tested whether the TT(-695/-694)GC polymorphism is
associated with differences in (1) myocardial Gq protein expression, (2) vascular
reactivity, and (3) myocardial damage after coronary artery bypass grafting.
METHODS: Gq protein expression was measured in right atrial muscle from 55
patients undergoing coronary artery bypass grafting as were skin perfusion
changes (n = 18; laser Doppler imaging), saphenous vein ring vascular reactivity
(n = 50, organ bath) in response to angiotensin II, and myocardial damage (227
patients undergoing coronary artery bypass grafting), as assessed by
postoperative cardiac troponin I concentration. RESULTS: Myocardial Gq expression
was greater in GC/GC genotypes (GC/GC vs. TT/TT: 1.27-fold change; P = 0.006).
Skin perfusion after intradermal angiotensin II injection decreased only in GC/GC
genotypes (P = 0.0002). Saphenous vein rings exposed to increasing angiotensin II
concentrations showed an almost doubled maximum contraction in GC/GC compared
with individuals with the TT/TT genotype (P = 0.022). In patients undergoing
coronary artery bypass grafting, baseline cardiac ejection fraction was different
(GC/GC: 55 +/- 13%; GC/TT: 54 +/- 14%; TT/TT: 48 +/- 15%; P = 0.037) and
postoperative peak cardiac troponin I was greater in patients with the GC/GC
(11.5 +/- 13.8 ng/ml) than in patients with the GC/TT (9.2 +/- 9.2 ng/ml) or
patients with the TT/TT genotype (6.6 +/- 4.8 ng/ml, P = 0.015). CONCLUSIONS: The
GC/GC genotype of the TT(-695/-694)GC polymorphism is associated with increased
Gq protein expression, augmented angiotensin II receptor type 1-related
vasoconstriction, and increased myocardial injury after coronary artery bypass
grafting, highlighting the impact of Gq genotype variation.
PMID- 28422820
TI - Comparison of the ETView Single Lumen and Macintosh laryngoscopes for
endotracheal intubation in an airway manikin with immobilized cervical spine by
novice paramedics: A randomized crossover manikin trial.
AB - CONTEXT: Management of the airway of a trauma victim is considered challenging.
Various approaches have been described to achieve airway control in this setup;
many of them include video-assited viewing of the larynx during intubation.
ETView Single Lumen (SL) is a novice single-use endotracheal tube equiped with a
video camera and a light source at its distal tip. Its use was previously
described in seeral clinical and training setups. OBJECTIVE: The aim was to
evaluate the efficacy of the VivaSight SL compared with classic direct
laryngoscopy performed with a Macintosh blade in a manikin-simulated trauma setup
presenting various degrees of airway challenge when performed by inexperienced
physicians. DESIGN, SETTING, PARTICIPANTS: This was prospective, randomized,
crossover, manikin trial. After short training on the ETView system, 67 novice
paramedics attempted to perform oral intubation using both standard direct
laryngoscopy (MAC group) and the VivaSight SL endotracheal tube (ETView group) in
a randomized order on manikins in 3 increasingly more difficult scenarios (simple
intubation, cervical spine manual stabilization, and with cervical collar in
place). OUTCOME MEASURE: Overall success rate, time to intubation, number of
intubation attempts, laryngeal view grade, dental compression, and overall
participant satisfaction were monitored. RESULTS: Duration of intubation and
number of attempts were significantly superior in the ETView group in the latter
2 more challenging scenarios. All other parameters showed superiority to the
ETView group in all 3 scenarios. CONCLUSION: The VivaSight SL system performed
better in a complex scenario of airway management of a trauma victim in need for
cervical spine stabilization performed by novice caregivers compared to standard
direct laryngoscopy and should be considered in this clinical setup.
PMID- 28422821
TI - How the cognitive reserve interacts with beta-amyloid deposition in mitigating
FDG metabolism: An observational study.
AB - This observational study had the aim to assess the interaction between cognitive
reserve (CR) and cerebrospinal fluid beta-amyloid1-42 (Abeta1-42) in modulating
brain [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism
in patients with moderate Alzheimer disease (AD).Twenty-seven patients with
probable AD and 25 neurological normal subjects (NNS) entered the study. All
participants had an FDG-PET scan, and AD patients also received a lumbar puncture
to measure Abeta1-42, 181p-tau, and Tau concentrations. Based on years of formal
education, AD patients were classified as highly educated-AD (years of formal
education >5) or less educated-AD (years of formal education <5). By using a
voxel-wise approach, we first investigated differences in the cerebral glucose
uptake between AD and NNS, then we assessed the interaction between level of
education (a proxy of CR) and cerebrospinal fluid biomarkers on FDG-PET
metabolism in the patient groups.Significantly lower glucose uptake was observed
in the posterior cingulate gyrus, in the precuneus, in the inferior and medial
temporal gyrus, and in the inferior parietal lobule of AD patients compared with
NNS. A significant interaction was found between CR and Abeta1-42 values on brain
metabolism in the inferior and medial temporal gyrus bilaterally.The AD patients
with higher CR level and marked signs of neuropathology showed glucose
hypometabolism in regions typically targeted by AD pathology. This finding
supports the hypothesis that CR partially compensates for the effect of Abeta
plaques on cognitive impairment, helps in patients' clinical staging, and opens
new possibilities for the development of nonpharmacological interventions.
PMID- 28422822
TI - Intraoperative centration during small incision lenticule extraction (SMILE).
AB - To evaluate intraoperative decentration from pupil center and kappa intercept
during small incision lenticule extraction (SMILE) and its impact on visual
outcomes.This was a retrospective noncomparative case series. A total of 164 eyes
that underwent SMILE at the Singapore National Eye Center were included. Screen
captures of intraoperative videos were analyzed. Preoperative and 3 month
postoperative vision and refractive data were analyzed against decentration.The
mean preoperative spherical equivalent (SE) was -5.84 +/- 1.77. The mean
decentration from the pupil center and from kappa intercept were 0.13 +/- 0.06 mm
and 0.47mm +/- 0.25 mm, respectively. For efficacy and predictability, 69.6% and
95.0% of eyes achieved a visual acuity (VA) of 20/20 and 20/30, respectively,
while 83.8% and 97.2% of eyes were within +/-0.5D and +/-1.0D of the targeted SE.
When analyzed across 3 groups of decentration from the pupil center (<0.1 mm, 0.1
0.2 mm, and >0.2 mm), there was no statistically significant association between
decentration, safety, efficacy, and predictability. When analyzed across 4 groups
of decentration from kappa intercept (<0.2 mm, 0.2-<0.4 mm, 0.4-<0.6 mm, and
>=0.6 mm), there was a trend toward higher efficacy for eyes with decentration of
kappa intercept between 0.4 and <0.6 mm (P = .097). A total of 85.4% of eyes in
the 0.4 to <0.6 mm group had unaided distance VA of 20/20 or better, as compared
to only 57.8% of eyes in >=0.6 mm group.Decentration of 0.13 mm from the pupil
center does not result in compromised visual outcomes. Decentration of greater
than 0.6 mm from the kappa intercept may result in compromised visual outcomes.
There was a trend toward better efficacy in eyes which had decentered treatment
from 0.4 to <0.6 mm from the kappa intercept. Patients with a large kappa
intercept (>0.6 mm) should have their lenticule created 0.4 to 0.6 mm from the
kappa intercept and not close to the pupil.
PMID- 28422823
TI - Association between ALDH2 Glu487Lys polymorphism and the risk of esophageal
cancer.
AB - OBJECTIVE: A meta-analysis was carried out to further evaluate the relationship
between ALDH2 Glu487Lys polymorphism and esophageal cancer risk. METHODS: A total
number of 15 studies that included 3812 cases and 7376 controls were identified
for our meta-analysis. RESULTS: Our findings indicated that individuals with the
combination of Glu/Lys and Lys/Lys genotype had an increased risk of getting
esophageal cancer (GA + AA vs. GG: odds ratio [OR] 1.36, 95% confidence interval
[CI] 0.93-2.00, P = 0.113) with a shift pattern. Although Lys/Lys genotype
carriers showed areduced esophageal cancer risk (AA vs. GA + GG: OR 0.41, 95% CI
0.23-0.72, P = 0.002). Similarly, a negative association was observed under
homozygote comparison (AA vs. GG: OR 0.49, 95% CI 0.29-0.85, P = 0.011). In the
China subgroup analysis, the similar results were found. CONCLUSIONS: This meta
analysis concluded that there was a strong association between ALDH2 Glu487Lys
polymorphism and the risk of esophageal cancer. It further confirmed that ALDH2
Glu487Lys polymorphism was a high-risk factor for esophageal cancer.
PMID- 28422824
TI - Pancreatic carcinoids (serotonin-producing pancreatic neuroendocrine neoplasms):
Report of 5 cases and review of the literature.
AB - INTRODUCTION: Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare
tumors representing 1% to 2% of all pancreatic neoplasms. These tumors can
secrete a variety of biologically active substances giving rise to distinct
clinical symptoms or can be clinically nonfunctioning. Apart from insulinomas and
gastrinomas, which constitute the majority of functioning pNENs, some tumors may
secrete serotonin presenting with the features of the carcinoid syndrome. These
so-called pancreatic carcinoids are considered relatively rare tumors and are
associated with increased urinary levels of 5-hydroxyindoleacetic acid (5-HIAA).
It has recently been suggested that the prevalence of such tumors might be
underestimated. CASES: We present a series of 5 patients from our database of 138
pNENs (5/138, 3.62%), harboring serotonin-producing pNENs and describe their
distinctive clinical, biochemical, histopathological features, and response to
treatment along with a review of the relevant available literature. CONCLUSION:
Such tumors are considered rare, although this may be an underestimate as
systematic screening for the presence of serotonin in tissue or elevated urinary
5-HIAA levels in patients with apparently nonfunctioning pNENs is not currently
recommended. In order to reach such a consensus, data from large prospective
studies are needed in order to evaluate the impact of this type of tumors in
survival and clinical outcome, since some studies have suggested a worse
prognosis.
PMID- 28422825
TI - Interdigitating dendritic cell sarcoma presenting in the sigmoid colon mesentery:
A case report and literature review.
AB - RATIONALE: Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare
disease. It commonly occurs in middle-aged males and mainly involves the lymph
nodes. Pathological examination plays an important role in differentiating from
other tumors, but far less published literature focuses on the imaging
characteristics of IDCS. PATIENT CONCERNS: Here, we reported a case of IDCS in a
52-year-old male involving the pelvis with medical imaging and pathologic
findings. DIAGNOSES: Preoperative unenhanced CT scan revealed a 6.0 * 6.3 * 8.0
cm mass with density equal to that of adjacent muscle, located in the pelvis. On
contrast-enhanced CT images, the tumor presented apparent homogeneous
enhancement. CT angiography showed that the tumor was supplied by the branches of
inferior mesenteric artery. Pelvic magnetic resonance imaging manifested a
lobulated solid mass with low signal on T1-weighted and intermediate to high
signal on T2-weighted images. Simultaneously, significantly high signal intensity
was exhibited on the diffusion-weighted images. This patient underwent operative
resection of the tumor. The pathologic diagnosis was IDCS. INTERVENTIONS: This
patient underwent operative resection of the tumor. The resection margins were
negative for the neoplastic proliferation and no distant metastases were found.
The patient did not receive advanced radiotherapy or chemotherapy. OUTCOMES:
Three months after surgery, the follow-up CT scan did not reveal any recurrence
or metastases. LESSONS: This case adds to the experience with IDCS by summarizing
its characteristics as well as reviewing the literature.
PMID- 28422826
TI - Idiopathic hypoparathyroidism with extensive intracranial calcification in
children: First report from Saudi Arabia.
AB - RATIONALE: Pediatric idiopathic hypoparathyroidism with extensive intracranial
calcifications outside the basal ganglia (BG) is extremely rare with less than 10
cases worldwide. PATIENT CONCERNS: An 11-year-old Saudi male child presented with
tetany with otherwise normal neurological and other body system examination
diagnoses severe hypocalcemia for differential diagnosis. INTERVENTIONS: Further
investigations revealed hyperphosphatemia and undetectable serum intact
parathyroid hormone. Brain computed tomography revealed BG and extensive brain
calcifications. He has no dysmorphic features, vitiligo, mucocuataneous
manifestations, or hair loss. He had normal hemoglobin, electroencephalogram, and
skeletal survey, with negative autoantibodies to alpha and omega interferons and
negative genetic testing for Glial Cell Missing 2 (GCM2) and calcium-sensing
receptors (CaSRs) excluding known causes of hypoparathyroidism. OUTCOMES: This
case presents a rare entity of idiopathic hypoparathyroidism with extensive
intracranial calcification, not only in BG but also outside the extrapyramidal
system with normal mentality, development, pubertal achievement, and neurological
examination. To our knowledge, this is the first report from Saudi Arabia in
pediatrics. LESSONS: Idiopathic hypoparathyroidism is a diagnosis of exclusion
after ruling out all known causes of hypoparathyroidism. It is associated with BG
calcifications, but extensive intracranial calcifications outside the BG are
extremely rare.
PMID- 28422827
TI - A case of a resected benign myxoma-like hemorrhagic cyst, which later recurred as
undifferentiated pleomorphic sarcoma in the left atrium.
AB - RATIONALE: An intracardiac cystic mass is a rare type of mass found in the left
atrium. The differential diagnosis of an intracardiac cystic mass includes
hydatid cysts, bronchogenic cysts, intracardiac varices, and hemorrhages in some
tumor types, including myxoma. PATIENT CONCERNS: We present the case of a 68-year
old woman who presented with episodic dyspnea. DIAGNOSES-INTERVENTIONS-OUTCOMES:
Transthoracic echocardiography (TTE) revealed the presence of a left atrial mass
mimicking myxoma. However, in postoperative findings, it was determined that the
mass was actually a hemorrhagic cyst. Eighteen months later, the patient
presented with recurrent exertional dyspnea and TTE revealed the recurrence of a
left atrial mass. Computed tomography showed that the mass extended into the
right atrium, inferior vena cava, and coronary sinus. After re-operation, the
final histological diagnosis was determined to be an undifferentiated pleomorphic
sarcoma in the left atrium. LESSONS: An intracardiac hemorrhagic cyst was
suspected during the operation of a benign-looking LA mass. As such, we recommend
that other rare etiologies be considered and more biopsies be performed when
possible.
PMID- 28422828
TI - Gastrointestinal Mucormycosis of the Jejunum in an Immunocompetent Patient: A
Case Report.
AB - RATIONALE: Gastrointestinal Mucormycosis (GIM) is a kind of opportunistic fungal
infection with poor prognosis. It usually occurs in patients with immune
deficiency. We reported a case of immunocompetent male patient. PATIENT CONCERNS:
This patient was presented as abdominal distension and gastrointestinal bleeding.
DIAGNOSES: A variety of hemostatic methods was ineffective to stop the bleeding.
The patient finally received laparotomy, and the jejunum lesions were found.
INTERVENTIONS: Pathological examination confirmed it to be gastrointestinal
mucormycosis in jejunum. OUTCOMES: However, after systemic anti-fungi therapy,
the patient died of septic shock. LESSONS: The diagnosis mainly relies on
pathological examination. Early diagnosis and early application of systemic
amphotericin B liposome were fundamental for improving the prognosis.
PMID- 28422829
TI - Impact of pain on cognitive functions in primary Sjogren syndrome with small
fiber neuropathy: 10 cases and a literature review.
AB - Primary Sjogren syndrome (pSS) is a chronic systemic autoimmune disease
characterized by xerophthalmia, xerostomia, and potential peripheral or central
neurological involvement. In pSS, the prevalence of cognitive disorders is
generally sparse across literature and the impact of pain on cognitive profile is
unclear. The aim of this study was to determine the relation between pain,
cognitive complaint, and impairment in a very homogenous population of 10 pSS
patients with painful small fiber neuropathy (PSFN) and spontaneous cognitive
complaint. Neurological exam, neuropsychological assessment, clinical evaluation
measuring pain level, fatigue, anxiety, depression, and cognitive complaint were
performed. Our results showed that 100% of patients had cognitive dysfunction
especially in executive domain (80%). The most sensitive test was the Wisconsin
Card Sorting Test (WCST), abnormal in 70% of our population. Moreover, we found
clear cut significant correlations between pain levels and 3 measures of WCST:
the number of errors (R = -0.768, P = .0062), perseverations (R = 0.831, P =
.0042), and categories (R = 0.705, P = .02). In the literature review, the impact
of pain is underexplored and results could be discordant. In a homogeneous cohort
of pSS patients with PSFN, a cognitive complaint seems to be a valid reflection
of cognitive dysfunction marked by a specific executive profile found with the
WCST. In this preliminary study, this profile is linked to the level of pain and
highlights that an appropriate management of pain control and a cognitive
readaptation in patients could improve the quality of life.
PMID- 28422830
TI - Management of the extensive thoracic defects after deep sternal wound infection
with the rectus abdominis myocutaneous flap: A retrospective case series.
AB - Deep sternal wound infection is a severe complication after open heart surgery.
According to the different severity and dimensions of the deep sternal wound
infection, the treatment method is different. In this study, we aimed to describe
our experience with the rectus abdominis myocutaneous flap for large sternal
wound management, especially when 1 or 2 internal mammary arteries were
absent.Between October 2010 and January 2016, a retrospective review of 9
patients who suffered from the extensive thoracic defects after deep sternal
wound infection was conducted. All of these sternal defects encompassed almost
the full length of the sternum after debridement. Defect reconstruction was
achieved by covering with a rectus abdominis myocutaneous flap. When the
ipsilateral or bilateral internal mammary artery had been harvested previously,
we took advantage of the inferior epigastric artery to provide additional blood
supply to the rectus abdominis myocutaneous flap. Thus, this flap had a double
blood supply.There was no recurrent infection in all 9 patients. Three patients
received the rectus abdominis myocutaneous flap with a double blood supply. Flap
complications occurred in 2 patients (22%). One patient who did not have the
double blood supply flap suffered from necrosis on the distal part of the flap,
which was then debrided and reconstructed with a split-skin graft. The other
patient had a seroma at the abdomen donor site and was managed conservatively.
None of the patients died during the hospital stay.This study suggests that the
rectus abdominis myocutaneous flap may be a good choice to repair the entire
length of sternal wound. When 1 or 2 internal mammary arteries have been
harvested, the inferior epigastric artery can be anastomosed to the second
intercostal artery or the internal mammary artery perforator to provide the
rectus abdominis myocutaneous flap with a double blood supply.
PMID- 28422831
TI - Association between diabetes mellitus and subsequent ovarian cancer in women: A
systematic review and meta-analysis of cohort studies.
AB - Epidemiologic studies have suggested that diabetes mellitus (DM) might be
associated with risk of ovarian cancer; however, the results have been
inconsistent. The aim of this study was to determine the relationship between DM
and the incidence of ovarian cancer on the basis of cohort studies.Relevant
studies from PubMed, Embase, and the Cochrane Library until September 2016 were
collected. The summary risk ratio (RR) was used as the effect measure in a random
effects model. Sensitivity analysis, subgroup analysis, and calculation of
publication bias were conducted.Thirteen articles including 14 cohorts comprising
a total of 3708, 313 women and reporting 5534 cases of ovarian cancer were
included. The summary RR suggested that patients with DM had a higher risk of
ovarian cancer than patients without DM (RR: 1.19; 95% confidence interval: 1.06
1.34; P = .004), and no evidence of publication bias was found. The subgroup
analysis indicated a higher incidence of ovarian cancer in patients with DM in
studies published after 2010, studies not conducted in Europe or the United
States, studies that did not adjust for body mass index or smoking status, and
studies with lower Newcastle-Ottawa Scale scores.The present findings indicated
that DM is a risk factor for ovarian cancer, and future large-scale epidemiologic
studies should be performed to evaluate this relation in specific populations.
PMID- 28422832
TI - Two year result of intravitreal bevacizumab for diabetic macular edema using
treat and extend protocol.
AB - To determine the efficacy of the treat and extend (TAE) protocol with
intravitreal bevacizumab (IVB) for managing diabetic macular edema
(DME).Retrospective, single-center study.For this retrospective study, 42 eyes of
42 patients were initially treated with 3 consecutive monthly IVB injections
(loading phase), after which they were selected for different additional
therapies. For the TAE protocol, the baseline treatment interval was selected to
be 8 weeks and was sequentially lengthened by 2 weeks if the central macular
thickness (CMT) was <300 MUm at 2 consecutive examinations.Among the 42 eyes, 8
eyes (19.0%) received the TAE treatment for 2 years. The BCVA was improved
significantly from 0.37 +/- 0.04 before treatment to 0.19 +/- 0.04 logMAR units
at 2 years after the TAE determined IVB injections (P < .05). The ratio of eyes
with a gain of the BCVA by more than 2 lines was 37.5%. The CMT was significantly
reduced from 515.4 +/- 75.5 to 303.6 +/- 45.0 MUm after 2 years (P < .01). The
mean number of TAE injection was 8.8 and the mean injection interval was 11.0
weeks.After the loading phase, 19.0% of patients can be treated with the TAE
protocol. Although significant visual improvements were obtained after the TAE
protocol, it does not apply to every DME case.
PMID- 28422833
TI - Correction of sagittal imbalance in treatment for adult degenerative scoliosis
with thoracic lordosis and lumbar kyphosis: A case report.
AB - RATIONALE: Lumbar degenerative scoliosis (LDS) is a common spinal disease for
senior citizens. However, LDS accompanied with thoracic lordosis and lumbar
kyphosis (LK) is rare in clinic. No reports have reported LDS with thoracic
lordosis and LK. PATIENT CONCERNS: A 54-year-old woman just complained about
sever back pain without any radiculopathy and neurodeficit of low limb for 2
years, Visual Analogue Scale (VAS) for back pain was 9 points and x-ray showed
adult LDS with lordosis angle of 10 degrees from 5th thoracic to 12th thoracic
(T5-T12) and LK angle of 20 degrees . DIAGNOSES: She was diagnosed with adult
degeneration scoliosis (ADS). INTERVENTIONS: The patient underwent posterior
pedicle screw implantation from L1 to S1 levels. OUTCOMES: Two weeks after
surgery, VAS for back pain was 2 points and x-ray showed thoracic lordosis angle
of 6 degrees , lumbar lordosis (LL) of 6 degrees and sagittal vertical axis from
C7 plumb line (SVA) of 77 mm. One year after surgery, VAS for back pain was 1
points and the x-ray showed thoracic lordosis angle of 6 degrees , LL of 20
degrees , and SVA of 36 mm, implying globe spine for this patient tends to
balance. LESSONS: Adult degenerative scoliosis accompanied with thoracic lordosis
and LK is rare. Correcting sagittal imbalance is an effective treatment. The
surgical outcome is satisfactory. Attention should be paid in sagittal balance
for treatment of ADS. We still need further follow-up to observe change of
sagittal parameters.
PMID- 28422834
TI - Feasibility and safety of emergency laparoscopic partial splenectomy: A
retrospective analysis.
AB - The increased awareness of asplenia-related life-threatening complications has
led to the development of parenchyma sparing splenic resections in past few
years. The aim of this study is to retrospectively analyze the feasibility and
safety of laparoscopic partial splenectomy (LPS) in selected emergency
patients.From January 2013 to December 2015, there were 46 emergency patients,
diagnosed with splenic rupture, admitted in our department. Selection criteria
for LPS: (1) Preoperative CT scan revealed single pole rupture without spleen
pedicle injury; (2) BP>90/60 mm Hg and heart rates <120 bpm; (3) No sigh of
multiple organ injury. Eventually, LPS was performed in 21 patients (Group LPS),
while laparoscopic splenectomy (LS) was performed in 20 patients (Group LS).The
main cause of splenic rupture was traffic accident, followed by blunt injury and
high falling injury. Abdominal CT scan showed the mean longitudinal diameter of
spleen of group LPS was 14.2 +/- 1.8 cm (range 12-17 cm), while the size of
remnant spleen was 5.5 +/- 1.2 cm. Between 2 groups, operation time (LPS: 122.6
+/- 17.2 min vs LS: 110.5 +/- 18.7 minutes, P = .117), and intraoperative blood
loss (LPS: 174 +/- 22 mL vs LS: 169 +/- 29 mL, P = .331) were similar. There were
2 patients suffered subsequent unstable vital sign altering during mobilization
when performing LPS. Conversion to LS (2/21, 9.52%) was decided and successfully
completed. Although there was no patient suffered postoperative OPSI or
thrombocytosis events in both groups after 6-month follow-up, the mean platelets
and leukocyte count were significantly lower in group LPS. Splenic regrowth was
evaluated in 20 patients of group LPS. And the mean regrowth of splenic volume
reached 19% (10%-26%).Due to its minimal invasive effect and functional splenic
tissue preservation, LPS may be a safe and feasible approach for emergency
patients. And prospective trials with clear inclusion criteria are needed to
proof the benefit of LPS.
PMID- 28422835
TI - Predictive factors of better outcomes by monotherapy of an antivascular
endothelial growth factor drug, ranibizumab, for diabetic macular edema in
clinical practice.
AB - Intravitreal ranibizumab (IVR) has been approved for treating diabetic macular
edema (DME), and is used in daily clinical practice. However, the treatment
efficacies of IVR monotherapy in real-world clinical settings are not well
known.The medical records of 56 eyes from 38 patients who received their first
IVR for DME between April 2014 and March 2015, and were retreated with IVR
monotherapy as needed with no rescue treatment, such as laser photocoagulation,
were retrospectively reviewed. The clinical course, best-corrected visual acuity
(BCVA), and fundus findings at baseline, before the initial IVR injection, and at
12 months, were evaluated.Twenty-five eyes from 25 patients (16 men; mean age
68.7 +/- 9.8 years) who received IVR in the first eye, or unilaterally, without
any other treatments during follow-up were included. After 12 months, mean
central retinal thickness (CRT), which includes edema, was reduced (P = .003),
although mean BCVA remained unchanged. There was a negative correlation between
individual changes in BCVA (r = -0.57; P = .003) and CRT (r = -0.60; P = .002) at
12 months compared with baseline values. BCVA changes were greater in individuals
with a history of pan-retinal photocoagulation at baseline (P = .026). After
adjusting for age and sex, CRT improvement >100 MUm at 12 months was associated
with a greater CRT at baseline (OR 0.87 per 10 MUm [95% CI 0.72-0.97]; P = .018)
according to logistic regression analyses; however, better BCVA and CRT at 12
months were associated with a better BCVA (r = 0.77; P < .001) and lower CRT (r =
0.41; P = .039) at baseline, respectively, according to linear regression
analyses.IVR monotherapy suppressed DME, and the effects varied according to
baseline conditions. Eyes that had poorer BCVA or greater CRT, or a history of
pan-retinal photocoagulation at baseline, demonstrated greater improvement with
IVR monotherapy. In contrast, to achieve better outcome values, DME eyes should
be treated before the BCVA and CRT deteriorate. These findings advance our
understanding of the optimal use of IVR for DME in daily clinical practice,
although further study is warranted.
PMID- 28422836
TI - Fecal microbiota transplantation is a rescue treatment modality for refractory
ulcerative colitis.
AB - BACKGROUND: Fecal microbial transplantation (FMT) provides to replace beneficial
bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of
the present study was to prospectively investigate the efficacy of FMT by
assessing the clinical and endoscopic response in patients with ulcerative
colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy.
METHODS: In this prospective and uncontrolled study, 30 patients with UC were
included. All medications except mesalazine were stopped 4 weeks before FMT.
Colonoscopy was performed both before and after FMT. To assess the efficacy of
FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL
extracted fresh fecal suspension was administered into the 30 to 40 cm proximal
of terminal ileum of recipients. RESULTS: After FMT, 21 of the (70%) 30 patients
showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and
endoscopic remission at the week 12. Nine patients (30%) were accepted as a
nonresponder at the end of the week 12. There was no significant difference among
donors concerning both the rate of clinical remission and clinical response. No
adverse events were observed in the majority of patients during FMT and 12 weeks
follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea,
vomiting, abdominal pain, diarrhea, and fewer after FMT. CONCLUSION: FMT could be
considered as a promising rescue treatment modality before surgery in patients
with refractory UC. Besides, FMT also appears to be definitely safer and more
tolerable than the immunosuppressive therapy in patients with UC (NCT02575040).
PMID- 28422837
TI - Multilevel cervical disc replacement versus multilevel anterior discectomy and
fusion: A meta-analysis.
AB - BACKGROUND: Cervical disc replacement (CDR) has been developed as an alternative
surgical procedure to anterior cervical discectomy and fusion (ACDF) for the
treatment of single-level cervical degenerative disc disease. However, patients
with multilevel cervical degenerative disc disease (MCDDD) are common in our
clinic. Multilevel CDR is less established compared with multilevel ACDF. This
study aims to compare the outcomes and evaluate safety and efficacy of CDR versus
ACDF for the treatment of MCDDD. METHODS: A meta-analysis was performed for
articles published up until August 2016. Randomized controlled trials (RCTs) and
prospective comparative studies associated with the use of CDR versus ACDF for
the treatment of MCDDD were included in the current study. Two reviewers
independently screened the articles and data following the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis statement. RESULTS: Seven studies
with 702 enrolled patients suffering from MCDDD were retrieved. Patients who
underwent CDR had similar operative times, blood loss, Neck Disability Index
(NDI) scores, and Visual Analog Scale (VAS) scores compared to patients who
underwent ACDF. Patients who underwent CDR had greater overall motion of the
cervical spine and the operated levels than patients who underwent ACDF. Patients
who underwent CDR also had lower rates of adjacent segment degeneration (ASD).
The rate of adverse events was significantly lower in the CDR group. CONCLUSION:
CDR may be a safe and effective surgical strategy for the treatment of MCDDD.
However, there is insufficient evidence to draw a strong conclusion due to
relatively low-quality evidence. Future long-term, multicenter, randomized, and
controlled studies are needed to validate the safety and efficacy of multilevel
CDR.
PMID- 28422838
TI - Opposite chromosome constitutions due to a familial translocation
t(1;21)(q43;q22) in 2 cousins with development delay and congenital anomalies: A
case report.
AB - RATIONALE: Chromosomal rearrangements are the major cause of multiple congenital
abnormalities and intellectual disability. PATIENT CONCERNS AND DIAGNOSIS: We
report 2 first cousins with unbalanced chromosomal aberrations of chromosomes 1
and 21, resulting from balanced familial translocation. Chromosome microarray
analysis revealed 8.5 Mb1q43q44 duplication/21q22.2q22.3 deletion and 6.8 Mb
1q43q44 deletion/21q22.2q22.3 duplication. Among other features, cognitive and
motor development delay and craniofacial anomalies are present in both patients,
whereas congenital heart defect and hearing impairment is only present in patient
carrying 1q43q44 duplication/21q22.2q22.3 deletion. LESSONS: In this report, we
provide detailed analysis of the phenotypic features of both patients as well as
compare our data with previously published reports of similar aberrations and
discuss possible functional effects of AKT3, CEP170, ZBTB18, DSCAM, and TMPRSS3
genes included in the deleted and/or duplicated regions. Partial trisomy
1q/monosomy 21q has only been reported once before, and this is the first report
of partial monosomy 1q/trisomy 21q. The expressed phenotype of mirroring
chromosomal aberrations in our patients supports the previous suggestion that the
dosage effect of some of the genes included in deleted/duplicated regions may
result in opposite phenotypes of the patients.
PMID- 28422839
TI - Unexpected side effect in mCRC: A care-compliant case report of regorafenib
induced hyperammonemic encephalopathy.
AB - RATIONALE: Regorafenib represents a treatment option in heavily pretreated
patients affected by metastatic colorectal cancer (mCRC). Its safety profile is
typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse
events are manageable. PATIENT CONCERNS: A 56 years-old Caucasian man affected by
mCRC with normal hepatic reserve was treated with regorafenib as second-line
treatment. After only 2 days of therapy, the patient presented to the emergency
department due to impairment of both spatial and temporal orientation and motor
function with bradylalia. INTERVENTIONS: Serum ammonia level was 191 mmol/L,
liver function tests and complete blood count were normal. Regorafenib was
withheld and branched chain amino acids and lactulose were administered.
OUTCOMES: Serum ammonia level returned within the normal range, but when
regorafenib was restarted at a lower dose level, a new episode of acute confusion
arised. MAIN LESSON: Discontinuation of regorafenib after confirmation of
hyperammonemia is strongly recommended; reintroduction of the therapy at lower
doses after resolution of symptoms related to hyperammonemic encephalopathy has
to be discouraged.
PMID- 28422840
TI - Case report: A female case of isolated IgG4-related sclerosing cholangitis
mimicking cholangiocarcinoma.
AB - RATIONALE: IgG4-related disease is a newly recognized fibroinflammatory disorder,
characterized by tumefactive lesions, storiform fibrosis and IgG4-positive plasma
cells infiltration. IgG4-related sclerosing cholangitis (IgG4-SC) is the most
common extrapancreatic manifestation of IgG4-related disease, but it is
frequently associated with autoimmune pancreatitis(AIP). Only few case was
reported to be diagnosed with IgG4-SC in the absence of AIP, with a striking male
preponderance. Here we report a female case of isolated IgG4 related sclerosing
cholangitis mimicking cholangiocarcinoma. PATIENT CONCERNS: A 58-year-old woman
complaint of one-month history of jaundice and right upper quadrant discomfort,
and the biliary reconstruction showed full-length wall thickening and segmental
stenosis. DIAGNOSES: Cholangiocarcinoma was then diagnosed. INTERVENTIONS:
Choledochoplasty was performed, followed by Roux-en-Y anastomosis. OUTCOMES:
However, pathological examination revealed IgG4-related sclerosing cholangitis
(IgG4-SC) and the retrospective measurement of serum IgG4 was 346 mg/dL post
operatively. The patient was followed for another nine monthswithout recurrence.
LESSONS: The differential diagnosis between cholangiocarcinoma and IgG4-SC is
challenging due to significant overlap of clinical manifestations, lab tests and
imaging characteristics. However, as an afterthought of this case, typical
cholangiocarcinoma rarely presents full-length wall thickening. What the case
taught us was pre-operative IgG4 measurement for patients with long bile duct
involvement was highly recommended in order to rule out IgG4-SC.
PMID- 28422841
TI - Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with
advanced pancreatic adenocarcinoma.
AB - To evaluate gemcitabine efficacy in advanced pancreatic cancer patients after the
FOLFIRINOX regimen.Patients with locally-advanced or metastatic pancreatic
adenocarcinoma from French and Canadian centers, who were treated with the first
line FOLFIRINOX regimen (FFX L1), followed by gemcitabine monotherapy as a second
line treatment (GEM L2), were retrospectively evaluated. Statistical analyses
were performed on the demographic, toxicity, and response rate data. Overall
survival (OS) and progression-free survival (PFS) were assessed using the Kaplan
Meier method.Seventy-two patients were reviewed (median age of 63.5 years [range,
32-75 years], men [62%], predominantly pancreatic head tumor location [51%] and
metastatic disease [64%] at the time of diagnosis). The objective response rate
to GEM-L2 treatment was 8/72 (11%), and 32 patients (44%) experienced a clinical
benefit from gemcitabine. Four patients had a partial response to GEM-L2,
although they previously showed a progressive response following FFX-L1
treatment. The median OS for the entire cohort was 13.6 months (95% confidence
interval [CI]: 2.0-35). The median PFS of the GEM-L2 group was 2.5 months (95%
CI: 0.2-10.8) with no statistical differences between patients with controlled or
progressive disease on FFX-L1 therapy.Gemcitabine as a second-line treatment for
advanced pancreatic adenocarcinoma after FOLFIRINOX failure showed clinical
benefits in some patients.
PMID- 28422842
TI - The role of renoscintigraphy and surgery in the management of Page kidney: A case
report.
AB - RATIONALE: Page kidney is an uncommon condition that hypertension occurs
secondary to microvascular ischemia and alternation of small-vessel hemodynamics
due to external compression of renal parenchyma and activation of the renin
angiotensin-aldosterone system. There are no specific guidelines for the
management of Page kidney in the literatures. PATIENT CONCERNS: A 17-year-old
teenager who had Fontan procedure for tricuspid and pulmonary atresia in early
childhood suffered from sudden onset of severe left flank pain during cardiac
catheterization procedure. Left renal artery active bleeding with renal
parenchyma compression in association with renin-mediated hypertension led to the
diagnosis of Page kidney. DIAGNOSES: Page kidney was diagnosed in this case.
INTERVENTIONS: Urgent embolization was performed to treat left renal artery
active bleeding. Because of decreased renal function with elevation of serum
creatinine, inadequate blood pressure control with antihypertensive medication,
and poor renal blood flow of left kidney, open drainage of perirenal hematoma was
done 5 days after catheterization procedure. OUTCOMES: After the operation,
glomerular filtration rate improved immediately, and left flank pain and
hypertension resolved at discharge. LESSONS: The choice of the therapies for Page
kidney depended on the clinical presentation of each case. This case pointed out
the significance of renoscintigraphy and surgery in the management of Page
kidney.
PMID- 28422843
TI - Hypoxia-regulated human periodontal ligament cells via Wnt/beta-catenin signaling
pathway.
AB - BACKGROUND: The aim of this study is to investigate the effects of hypoxia on the
proliferation, morphology, migration ability, hypoxia inducible factor (HIF) 1
(HIF-1) expression, and the relationship with Wnt/beta-catenin signaling of human
periodontal ligament cells (hPDLCs) in vitro. METHODS: hPDLCs (4th passage)
cultured by the tissue culture method were randomly assigned to slight (5% O2),
severe hypoxia (1% O2) groups, and the control (21% O2) group, respectively. From
1st to 7th day, the optical density values were detected, and the growth curve
was described. Wound healing assay was done to observe the migration ability of
hPDLCs under various O2 conditions. Then reverse transcription quantitative real
time polymerase chain reaction (RT-qPCR) was used to detect the expression of
cementum-related genes and Wnt signaling pathway-related genes. Further, RT-qPCR,
Western blot, and immunofluorescence staining method were constructed to show HIF
expressions under different O2 concentrations in hPDLCs. RESULTS: The growth rate
of hPDLCs decreased with the reduction of O2 content by degree, and the
morphology of hPDLCs changed in different O2 contents. Besides, hPDLCs migrate
faster in 21% and 5% O2 than in 1% O2, and both the expressions of cementum
related genes and Wnt signaling pathway-related genes were raised under hypoxic
conditions. In addition, with the reduction of O2 concentration, the messenger
RNA and protein level expression of HIF were all increased, and HIF was gradually
transported from cytoplasm into the nucleus and in 1% O2 concentration, it was
mainly expressed in the nucleus. CONCLUSION: This finding demonstrated that
hypoxia was capable of suppressing the proliferation and migration ability,
changing the morphology of hPDLCs, and stabilizing HIF-1alpha against degradation
and promoting its translocation to the nucleus. Meanwhile, hypoxia may regulate
hPDLCs proliferation and cementogenic differentiation via Wnt/beta-catenin
signaling pathway, which may potentially provide a novel insight into the
etiology and treatment of periodontal diseases.
PMID- 28422844
TI - Ultrasound is helpful to differentiate Bethesda class III thyroid nodules: A
PRISMA-compliant systematic review and meta-analysis.
AB - BACKGROUND: Fine-needle aspiration (FNA) is the most dependable tool to triage
thyroid nodules for medical or surgical management. However, Bethesda class III
cytology, namely "follicular lesion of undetermined significance" (FLUS) or
"atypia of undetermined significance" (AUS), is a major limitation of the US-FNA
in assessing thyroid nodules. As the most important imaging method, ultrasound
(US) has a high efficacy in diagnosing thyroid nodules. This meta-analysis aimed
to assess the role of US in evaluating Bethesda class III thyroid nodules.
METHODS: With keywords "Undetermined Significance," "Bethesda Category III,"
"Bethesda system," "Cytological Subcategory," "AUS/FLUS," "Atypia of Undetermined
Significance," and "Ultrasound/US," papers in PubMed, Cochrane Library, Medline,
Web of Science, Embase, and Google Scholar from inception to December 2016 were
searched. A meta-analysis of these trials was then performed for evaluating the
diagnostic value of thyroid ultrasound in Bethesda Category III thyroid nodules.
RESULTS: Fourteen studies including 2405 nodules were analyzed. According to the
criteria for US diagnosis of thyroid nodules in each article, with any one of
suspicious features as indictors of malignancy, US had a pooled sensitivity of
0.75 (95% CI 0.72-0.78) and a pooled specificity of 0.48 (95% CI 0.45-0.50) in
evaluating Bethesda Class III Nodules. The pooled diagnostic odds ratio was 10.92
(95% CI 6.04-19.74). The overall area under the curve was 0.84 and the Q* index
was 0.77. With any 2 or 3 of US suspicious features as indictors of malignancy,
the sensitivity and specificity were 0.77 (95% CI 0.71-0.83) and 0.54 (95% CI
0.51-0.58), 0.66 (95% CI 0.59-0.73) and 0.71 (95% CI 0.68-0.74), respectively.
CONCLUSIONS: US was helpful for differentiating benign and malignant Bethesda
class III thyroid nodules, with the more suspicious features, the more likely to
be malignant.
PMID- 28422845
TI - Response to benzodiazepines and the clinical course in malignant catatonia
associated with schizophrenia: A case report.
AB - BACKGROUND: Malignant catatonia (MC) is a disorder consisting of catatonic
symptoms, hyperthermia, autonomic instability, and altered mental status.
Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a
variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments
providing rapid relief from MC. This case study reports a detailed clinical
course of a case of MC associated with schizophrenia initially diagnosed as NMS
that responded successfully to BZDs but not to dantrolene. CASE PRESENTATION: A
53-year-old man with schizophrenia was admitted to the psychiatric hospital
because of excitement, monologue, muscle rigidity, and insomnia. In the 3 days
before admission, the patient had discontinued his medications after his family
member's death. He presented with hyperthermia, tachycardia, hypertension,
excessive sweating, and an elevated serum creatine phosphokinase (CPK) level. On
the basis of these features, he was suspected to have NMS. The patient was
treated with dantrolene for 7 days without improvement despite having a
normalized serum CPK level. The patient was transferred to our university
hospital for an in-depth examination and treatment of his physical status.
Infection and pulmonary embolism were excluded as possible causes. To treat his
excitement and auditory hallucination, an intravenous drip (IVD) of haloperidol
was initiated, but this treatment increased the patient's catatonic and psychotic
symptoms, although his serum CPK level had remained within a normal range. As a
result, the treatment was changed to diazepam. After an IVD of diazepam, the
patient's symptoms rapidly improved, and the IVD was subsequently replaced with
oral administration of lorazepam. Eventually, the patient was diagnosed with MC
associated with schizophrenia. BZD therapy was dramatically effective.
CONCLUSION: Catatonia, MNS, and MC may be due to a common brain pathophysiology
and these conditions may be in a spectrum, although uncertainty in the boundaries
among conditions, and the BZD treatment may be useful. Most importantly,
catatonia has not been described as a subtype of schizophrenia on the basis of
the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, and
the medications for catatonia and schizophrenia are different. Antipsychotics are
not effective in relieving catatonia, or they may induce NMS, whereas BZDs are
effective for treating both MC and NMS.
PMID- 28422846
TI - Application of remifentanil for conscious sedation and analgesia in short-term
ERCP and EST surgery.
AB - This study aims to observe and evaluate the use of remifentanil in conscious
sedation and analgesia for the safety and comfort of patients undergoing short
term endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic
sphincterotomy (EST).Sixty-eight patients who underwent ERCP and EST were
randomly divided into two groups: research group and control group. Patients in
the research group were intravenously injected with remifentanil (80-2/3* age)
for 1 to 2 minutes, combined with the intravenous injection of propofol (20-30
mg) during the course of treatment. ERCP surgery was performed when Ramsay
sedation scale (RSS) score reached 2-3. During the surgery, patients were closely
monitored for cough symptoms, aspiration, and respiratory and circulatory system
performance, and timely treatment was performed. Sedative drugs were not given in
patients in the control group.In research group, the circulatory and respiratory
depression of patients was mild, only one patient needed to be treated, and there
was no arrhythmia requiring treatment. Five patients had respiratory depression
(blood oxygen saturation decreased to <90%), which was immediately corrected.
There were no interruptions during surgery due to body movement, cough, or
aspiration.The use of remifentanil for conscious sedation and analgesia can be
broadly applied in short-term ERCP, which greatly improves patient comfort during
the surgery. This approach may bear promise for a widespread use in future
clinical practice.
PMID- 28422847
TI - Correlation between Calpain-10 single-nucleotide polymorphisms and obstructive
sleep apnea/hypopnoea syndrome with ischemic stroke in a Chinese population: A
population-based study.
AB - BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common chronic
disorder which is followed by various complications. Calpain-10 belongs to a
commonly expressed member of the Calpain-like cysteine protease family, which
acts as risk marker for some diseases. The purpose of this study is to elucidate
correlation between Calpain-10 single-nucleotide polymorphisms (SNPs) and the
incidence of OSAHS followed by ischemic stroke (IS). METHODS: OSAHS patients were
divided as OSAHS + IS, OSAHS, and control groups, respectively.
Immunohistochemistry was performed for Calpain-10 protein expression, polymerase
chain reaction (PCR)-restriction fragment length polymorphism for detection of
gene polymorphisms of SNP 43 and SNP 19, and PCR-allele specific amplification
for SNP 44. Polysomnography was conducted to check the nocturnal polysomnography
indicators, and also Montreal Cognitive Assessment (MoCA), Scientific Data System
scores cognition and anxiety of patients, respectively. Logistic analysis was
used for the risky factors for OSAHS. RESULTS: Calpain-10 protein expression was
significantly increased in the OSAHS + IS and OSAHS groups compared with the
control group. Significant differences in SNP 43 and SNP 44 genotype, and also
allele frequency were observed in 3 groups, among which the OSAHS + IS group had
higher SNP 43 and SNP 44 allele frequency than the control and OSAHS groups.
There were differences regarding apnea-hypopnea index, minimum fingertip blood
oxygen saturation (LSaO2 [%]), oxygen reduction index (ODI) between patients with
different genotypes of SNP 43 and SNP 44 in OSAHS patients, and also GC and AT
frequency in the OSAHS + IS and OSAHS groups. As compared with the OSAHS group,
the MoCA scores and MoCA subitems in the OSAHS + IS group were declined, whereas
the Scientific Data System scores were elevated. Additionally, GG 43 genotype,
high apnea-hypopnea index, and body mass index were detected as the risk factors
of OSAHS. CONCLUSION: These findings indicate that the Calpain-10 SNP 43 may be
related to OSAHS with IS, with SNP 43 GG genotype as a risk factor for OSAHS with
IS.
PMID- 28422848
TI - Teriparatide as a nonoperative treatment for tibial and femoral fracture
nonunion: A case report.
AB - RATIONALE: Fracture nonunion is a great challenge for orthopedic surgeons. Many
surgical interventions are associated with significant pain and heavy economic
burden. Therefore, our aim was to evaluate the outcomes of a new nonoperative
treatment for fracture nonunion. PATIENT CONCERNS: A 44-year-old man suffered
closed fractures of the right tibia and left femur. Eleven months after surgery,
there was no radiographic healing between fracture fragments. DIAGNOSES: Fracture
nonunion of the right tibia and left femur. INTERVENTIONS: The patient received
systemic treatment with teriparatide (recombinant human Parathyroid Hormone 1-34)
20 MUg/d for 8 months, with further observation at 4 months after
discontinuation. During treatment, bone metabolic markers were measured to
evaluate metabolic activity of osteoblasts and osteoclasts. The Ethics Committee
of Qilu Hospital of Shandong University approved this study. OUTCOMES:
Satisfactory healing of fracture nonunion was obtained without further
intervention. LESSONS: Anabolic treatment with teriparatide showed a positive
effect on healing of fracture nonunion. Evaluation of bone metabolic markers
during treatment is necessary to observe the curative effect. In view of the
positive effect of teriparatide on healing of fracture nonunion in numerous
animal models and clinical studies, it may be a promising alternative treatment
for fracture nonunion in patients who are not suitable for surgical intervention.
PMID- 28422849
TI - Temporal trends in centralization and racial disparities in utilization of high
volume hospitals for lung cancer surgery.
AB - Racial disparities have been suggested in hospital utilization and outcome for
lung cancer surgery, but the effect of hospital centralization on closing this
gap is unknown. We hypothesized that centralization has increased the utilization
of high- or very-high-volume (HV/VHV) hospitals, a proxy for access to high
quality care, over the study period independently from race.Inpatient records
were extracted from the New York Statewide Planning and Research Cooperative
System database (1995-2012) according to Clinical Modification of the
International Classification of Diseases, 9th Revision diagnosis codes 162.* and
165.* and surgical procedure codes 32.2-32.6 (n = 31,931). Patients treated
exclusively with surgery of black or white race with a valid zip code were
included. Logistic models were performed to determine factors associated with
utilization of HV/VHV or low- or very-low-volume (LV/VLV) hospitals; these models
were subsequently stratified by race.The percentage of both black and white
patients utilizing HV/VHV hospitals increased over the study period (+22.7% and
13.9%, respectively). The distance to the nearest HV/VHV hospital and patient
hospital distance were significantly lower in black compared to white patients,
however, blacks were consistently less likely to use HV/VHV than whites (odds
ratioadj: 0.26; 95% confidence interval: 0.23-0.29), and were significantly more
likely to utilize urban, teaching, and lower volume hospitals than whites.
Likelihood of HV/VHV utilization decreased with an increasing distance from a
HV/VHV hospital, overall and separately for black and white patients.Although
centralization has increased the utilization of HV/VHV for both black and white
patients, racial differences in access and utilization of HV hospitals persisted.
PMID- 28422850
TI - Tuberculosis-associated hemophagocytic lymphohistiocytosis with initial
presentation of fever of unknown origin in a general hospital: An analysis of 8
clinical cases.
AB - The study aimed to investigate the clinical features and prognoses of patients
with tuberculosis (TB) who had secondary hemophagocytic lymphohistiocytosis
(HLH).Patients first presenting with fever of unknown origin, who were ultimately
diagnosed with TB-associated secondary HLH, were assessed retrospectively. We
summarized and analyzed clinical manifestations, laboratory examinations,
diagnoses, treatments, and prognoses of patients using clinical data, outpatient
follow-up, and telephone follow-up in combination with literature review.Among
patients admitted to the hospital with fever of unknown origin in the past 10
years, 371 patients were diagnosed with TB. Among them, 8 cases were diagnosed as
tuberculosis-associated HLH (TB-HLH). The proportion of females among TB-HLH
patients was higher than the proportion of females among TB patients. Within the
same time period, 227 cases met the diagnostic criteria for HLH, among which TB
HLH patients accounted for 3.52% of the cases. None of the 8 TB-HLH patients had
underlying diseases, and a majority of them had short symptom durations, rapid
progression, along with multisystem and multiorgan dysfunctions. Their clinical
manifestations were inconsistent with the typical clinical manifestations and
imaging results characteristic of TB. Compared with patients with TB in our
hospital during the same period, the 8 TB-HLH patients had a higher proportion of
blood-disseminated TB and tuberculous meningitis. Apart from this, the
hematological damage in these patients was higher than the common clinical
manifestations of TB, and they also had a high proportion of respiratory failure.
All 8 TB-HLH patients received antitubercular therapy, and 6 of them were also
treated for HLH. However, their morbidity and mortality were significantly higher
than that for reported cases of TB-HLH cases, both domestically and abroad, which
may be attributed to the fever of unknown origin.Patients with TB-HLH had poor
prognoses and no specific clinical manifestations. Therefore, cases of atypical
TB and severe TB should be carefully monitored to achieve early diagnosis and
early intervention.
PMID- 28422851
TI - Relation between serum myokines and phase II cardiac rehabilitation.
AB - Patients with coronary heart disease or acute myocardial infarction after cardiac
catheterization with stenting referred for phase II cardiac rehabilitation (CR)
were grouped according to their preference. Cardio-pulmonary exercise testing
(CPET) was used to determine oxygen uptake ((Equation is included in full-text
article.)) at peak exercise and anaerobic threshold (AT). The control patients
received counseling only while the experiment group received 36 sessions of CR in
3 to 6 months. Exercise physiology parameters and serum myokines (myostatin,
insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) were measured pre-
and postrehabilitation.There were 29 patients in the experiment group and 10 in
the control group, with no significant differences in baseline parameters. The
experiment group had prominent progress in aerobic capacity and body composition
after CR, but their serum myokine concentrations did not change significantly.
Serum myostatin is positively correlated to peak (Equation is included in full
text article.)pre- and post-training, and pretraining AT (Equation is included in
full-text article.), after adjusting for age, sex, and body composition. Serum
IGF-1 is positively correlated with grip strength before training.Serum myostatin
level is positively correlated to aerobic capacity, and IGF-1 level is positively
correlated to grip strength in cardiac patients receiving CR.
PMID- 28422852
TI - Stage I lung adenocarcinoma: the value of quantitative CT in differentiating
pathological subtypes and predicting growth of subsolid nodules.
AB - The aim of this study was to investigate feasibility of quantitative computed
tomography (CT) measurements in predicting invasiveness and growth of nodular
ground glass opacities (nGGOs).A set of 203 patients (group A) with nGGOs that
were confirmed stage-I adenocarcinomas and 79 patients (group B) with nGGOs that
were completely followed up were included. Lesions diameters, volume (VOL),
maximum (MAX), mean (MEN), and standard deviation (STD) of CT attenuation were
measured. P53 labeling index (LI) was evaluated through immunohistochemistry in
group-A patients. Multivariate linear stepwise regressions were performed based
on group-A lesions to calculate P53-LI prediction from CT measurements. The
receiver operating characteristic (ROC) curve analyses were performed to assess
the performance of P53-LI prediction in predicting invasiveness and growth of
nGGOs. The Cox regression analysis was conducted to identify correlation between
P53-LI Prediction and volume doubling time (VDT) of lesions in group B.Diameter,
VOL, MEN, STD, and the P53 LI showed significant differences between lesions of
different pathological invasiveness (P < .01). By multivariate linear
regressions, MEN and STD were identified as independent variables indicating P53
LI (P < .001); thus, an equation was established to calculate P53-LI Prediction
as: P53LI Prediction = 0.013 * MEN + 0.024 * STD + 9.741 (R square = 0.411, P <
.001). The P53-LI Prediction showed good performance, similar as the actual one,
in differentiating pathological invasiveness of nGGOs. In addition, the P53-LI
Prediction demonstrated excellent performance in predicting growth of nGGOs (AUC
= 0.833, P < .001) and independently forecasted VDT of nGGOs (beta = 1.773, P <
.001).The P53-LI Prediction that was calculated from preoperative quantitative CT
measurements of nGGOs indicates lesions' invasiveness and allows for predicting
growth of nGGOs.
PMID- 28422853
TI - Gastritis in patients undergoing sleeve gastrectomy: Prevalence, ethnic
distribution, and impact on glycemic.
AB - Laparoscopic sleeve gastrectomy (LSG) is a therapeutic option in severely obese
patients. The aim of this study was to evaluate the presence of Helicobacter
pylori (HP) gastritis and non-Helicobacter gastritis in the gastrectomy
specimens, and its association to other variables.One hundred six sleeve
gastrectomy specimens were examined histopathologically for the presence of
gastritis and its relation to other factors like ethnicity, glycemic control, and
postoperative complications.Twelve patients had HP gastritis, 39 had non-HP
gastritis, and 55 had normal mucosa. There was a statistical difference between
the Arab and Jewish Israeli patients in our study. Twenty-eight of the Arab
patients had HP gastritis and 48% had non-HP gastritis. In the Jewish population
6% had HP gastritis and 34% had non-HP gastritis. The preoperative glycemic
control was worse in the gastritis group with a mean HbA1c of 8.344% while in the
normal mucosa group the mean HbA1c was 6.55. After operation the glycemic control
reverted to normal in most the diabetic patients. There were few postoperative
complications however, they were not related to HP.There is a high incidence of
gastritis in obese patients. The incidence of gastritis in the Arab population in
our study was higher than that in the Jewish population. The glycemic control
before surgery was worse in patients with gastritis than in the normal mucosa
group. HP bares no risk for postoperative complications after LSG and does not
affect weight loss. However a larger cohort of patients must be studied to arrive
at conclusive results.
PMID- 28422854
TI - Immunohistological analysis of active sacroiliitis in patients with axial
spondyloarthritis.
AB - The sacroiliac joints (SIJs) are one of the most common sites involved in axial
spondyloarthritis (axSpA), and there are few studies on the histopathology of the
SIJ in this group of patients.Mononuclear cell infiltrates in the bone marrow and
fibrous tissue resembling a pannus formation were the pathological features of
early sacroiliitis in our previous study. We undertook a further
immunohistological evaluation of these features in patients with axSpA.Biopsy
specimens from the SIJ of 6 patients with established ankylosing spondylitis (AS)
and 13 patients with nonradiographic axial spondyloarthritis (nr-axSpA) were
analyzed. An immunohistological method was performed to examine the macrophages
(CD163), T cells (CD3), and B cells (CD20).Mononuclear cell infiltrates in the
bone marrow were observed in only 6 patients with nr-axSpA. Fibrous tissue was
observed in all patients with established AS and 9 patients with nr-axSpA.
Macrophage, T cell, and B cell infiltrates could be detected in both the bone
marrow and fibrous tissue. All bone marrow specimens from 6 nr-axSpA patients
exhibited CD163+ macrophage infiltrates; of these, 5 exhibited CD20+ B cell
infiltrates and 3 exhibited CD3+ T cell infiltrates. Among the fibrous tissue
specimens, all exhibited macrophage infiltrates, 9 exhibited B cell infiltrates,
and 4 exhibited T cell infiltrates.In addition to macrophages and T cells, B
cells are also involved in active sacroiliitis in patients with axSpA.
PMID- 28422855
TI - Thymalfasin, a promising adjuvant therapy in small hepatocellular carcinoma after
liver resection.
AB - There is limited information available concerning the effect of thymalfasin
(Talpha1) as an adjuvant therapy in hepatocellular carcinoma (HCC) patient who
received liver resection. The present study aimed to evaluate whether Talpha1 can
improve the prognosis of small HCC patients after liver resection.A total of 206
patients with small HCC who underwent liver resection were analyzed in our
retrospective cohort study. Patients were divided into 2 groups: group A
(resection + Talpha1, n = 44) and group B (resection, n = 162). Clinical data,
overall survival (OS), and recurrence-free survival (RFS) were compared.
Prognostic factors were identified using multivariate analysis.After a median
follow-up of 47.0 months, 134 patients (65%) had recurrence, and 62 patients
(30.09%) died. The 1, 3, and 5-year OS rate of patients in group A was 97.7%,
90.6%, and 82.9%, respectively, and 95.1%, 80.5%, and 62.9%, respectively, for
patients in group B (P = .014). The 1, 3, and 5-year RFS rate of patients in
group A was 70.5%, 56.8%, and 53.3%, respectively, and 65.8%, 41.3%, and 32.1%,
respectively, for patients in group B (P = .015). Multivariate analysis indicated
that Talpha1 was an independent prognostic factor for both OS (P = .015, hazard
ratio 0.349, 95% confidence interval 0.149-0.816) and RFS (P = .019, hazard ratio
0.564, 95% confidence interval 0.349-0.910).Talpha1 as an adjuvant therapy after
liver resection may improve the prognosis of small HCC patients after liver
resection.
PMID- 28422856
TI - A cross-sectional evaluation of meditation experience on electroencephalography
data by artificial neural network and support vector machine classifiers.
AB - To quantitate the meditation experience is a subjective and complex issue because
it is confounded by many factors such as emotional state, method of meditation,
and personal physical condition. In this study, we propose a strategy with a
cross-sectional analysis to evaluate the meditation experience with 2 artificial
intelligence techniques: artificial neural network and support vector machine.
Within this analysis system, 3 features of the electroencephalography alpha
spectrum and variant normalizing scaling are manipulated as the evaluating
variables for the detection of accuracy. Thereafter, by modulating the sliding
window (the period of the analyzed data) and shifting interval of the window (the
time interval to shift the analyzed data), the effect of immediate analysis for
the 2 methods is compared. This analysis system is performed on 3 meditation
groups, categorizing their meditation experiences in 10-year intervals from
novice to junior and to senior. After an exhausted calculation and cross
validation across all variables, the high accuracy rate >98% is achievable under
the criterion of 0.5-minute sliding window and 2 seconds shifting interval for
both methods. In a word, the minimum analyzable data length is 0.5 minute and the
minimum recognizable temporal resolution is 2 seconds in the decision of
meditative classification. Our proposed classifier of the meditation experience
promotes a rapid evaluation system to distinguish meditation experience and a
beneficial utilization of artificial techniques for the big-data analysis.
PMID- 28422857
TI - Serum resistin positively correlates with serum lipids, but not with insulin
resistance, in first-degree relatives of type-2 diabetes patients: an
observational study in China.
AB - To investigate whether serum resistin correlated with hypertension, obesity,
dyslipidemia, or insulin resistance (IR) in Chinese type 2 diabetes mellitus
(T2DM) patients and their first-degree relatives (DFDRs) in a case-control
observational study.We determined the serum levels of resistin, plasma lipids,
glucose, and insulin, and performed clinical assessments of hypertension,
obesity, and IR for 42 T2DM patients, 74 of their DFDRs, and 51 healthy control
participants with no family history of T2DM (NC group). The biochemical and
clinical variables were compared between the 3 groups, and relationships between
serum resistin and the other variables were evaluated using a Pearson correlation
analysis.Significant trends were observed in the triglyceride, HbA1c, and
resistin levels, in which the values observed in the DFDR group were intermediate
to those of the T2DM and NC groups (P < .05 for all). A stratified analysis
revealed significant trends in the resistin level and scores for homeostasis
model assessment (HOMA) indexes for IR and insulin sensitivity in women and in
the HbA1c and resistin levels in men (P < .05 for all), with DFDR subjects
exhibiting intermediate values. The Pearson analysis showed that serum resistin
positively correlated with total cholesterol and low-density lipoprotein
cholesterol in the DFDR group only (P < .05 for both), and that resistin did not
correlate significantly with HOMA indexes, blood glucose, insulin, HbA1c,
triglyceride, high-density lipoprotein cholesterol, BMI, waist or hip
circumference, or blood pressure.Our results suggest that elevated serum resistin
might contribute to an increased risk of hyperlipidemia in DFDRs of Chinese T2DM
patients.
PMID- 28422858
TI - 350-560 MUm gelatin sponge particles combined with transcatheter arterial
chemoembolization for the treatment of elderly hepatocellular carcinoma: The
safety and efficacy.
AB - To retrospectively analyze the safety and efficacy of 350-560 MUm gelatin sponge
particles combined with single-chemotherapy drug transcatheter arterial
chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma
without surgical resection.Thirty elderly hepatocellular carcinoma patients
without surgical resection, who received Gs-TACE in our hospital, were selected.
Slowly injected gelatin sponge particles (350-560 MUm)+ 10 mg lobaplatin
injection into the regional embolization tumor target vessel. The Response
Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response
after intervention surgery.Eighty-nine times of intervention TACE were conducted
on the 30 patients. The average size of tumor was 8.3 cm. The median survival
time was 28 months, and the 1 and 2-year survival rates were 89% and 58%,
respectively. The Response Evaluation Criteria for Solid Tumors was used to
evaluate the tumor response, and found that the complete response, partial
response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after
intervention surgery. The patients were divided into groups: 60 to 65 years age
group (A), >65 to 75 years age group (B), and >75 years age group (C); the median
survival times were 16, 32, and 33 months, respectively, and there was
statistical difference between A group, B group, and C group. The analysis of
prognosis factors showed that there was statistical significance in age,
Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal
protein (AFP), and age was the protective factor.Gelatin sponge particles (350
560 MUm), combined with transcatheter arterial chemoembolization, provide an
alternative method for the treatment of elderly hepatocellular carcinoma without
surgical resection.
PMID- 28422859
TI - The levels of triglyceride and total cholesterol in methamphetamine dependence.
AB - The serum triglyceride (TG) and total cholesterol (TC) levels have been reported
altered in the traditional drug-dependence (such as marijuana and heroin).
However, studies assessing the relationships among serum TC, TG, and
methamphetamine (MA)-dependence have not been described well. In this study, our
aim is to explore the serum TG and TC levels in large sample of MA-dependent
patients. A retrospective study was conducted in 938 MA-dependent patients who
were recruited between February 2, 2008 and March 11, 2013, with social
characteristics and drug-dependence history (duration of MA use, routes of drug
administration, and daily dose were collected). Then, the serum levels of TC, TG,
glucose (GLU), body mass index (BMI), and blood pressure were measured among the
participants. Meanwhile, 985 age- and gender-matched healthy people in the
physical examination center were selected as control group. Compared with the
control group, significant decreases of TC, TG, GLU, and BMI were observed in MA
dependent patients (P < 0.05). Besides, we found that the daily dose of MA use
was associated with TC (beta = -0.079, P = 0.015) and the duration of MA use was
independently related to BMI (beta = -0.071, P = 0.031). This study demonstrated
that the levels of TC, TG, GLU, and BMI factors altered in the MA-dependent
patients. In addition, there is a negative association between MA dependence and
TC and BMI.
PMID- 28422860
TI - Primary spinal glioblastoma multiforme: A case report and review of the
literature.
AB - RATIONALE: Primary spinal glioblastoma multiforme (GBM) is a rare clinical entity
with an aggressive course and an invariably dismal prognosis. Its clinical
characteristics, radiologic and pathologic findings, and treatment protocols have
been discussed in a few cases. PATIENT CONCERNS: A 15-year-old female was
admitted to the neurology department with a chief complaint of progressive
numbness and weakness in her left upper extremity for 3 months and neck pain for
1 month. DIAGNOSES: Spinal magnetic resonance imaging showed an intramedullary
expansile mass localized between C4 and C7. The diagnosis of GBM was determined
on the basis of the histopathological findings after operation. INTERVENTIONS:
Laminotomy and laminoplasty between C4 and C7 were performed, and the tumor was
partially resected. The patient was administered focal adjuvant radiotherapy
concomitantly with oral chemotherapy following the surgery. OUTCOMES: With severe
neurologic deficits at 13 months after the diagnosis, the patient expired.
LESSONS: Although therapeutic options have been improving, the prognosis of the
primary spinal GBM remains poor. The treatment of primary spinal GBM entered into
a central registry and multiple-center cooperation is important in establishing
future therapeutic strategies.
PMID- 28422861
TI - Does long-term efficacy differ between infliximab and adalimumab after 1 year of
continuous administration?: A STROBE-compliant retrospective cohort study.
AB - Although biologics are important inflammatory bowel disease therapies, loss of
response (LOR) remains problematic. We evaluated LOR to biologics in our Crohn
disease (CD) patients receiving biologics. Of 137 biologic-treated CD patients,
68 continuously receiving the same biologic type for at least 1 year were divided
into 2 groups: infliximab (IFX) (n = 39) and adalimumab (ADA) (n = 29). Clinical
courses were compared at biologic introduction and at 1 year. Both groups were
retrospectively analyzed for LOR at and beyond 1 year after biologic introduction
(study endpoint). Patients were then divided into LOR and non-LOR groups to
identify factors predicting LOR. At 1 year after biologic introduction, decreases
in CD activity index were 94 +/- 105 in the IFX and 102 +/- 89 in the ADA group,
not significantly different. Blood test data did not differ between these groups.
LOR occurred in 14 IFX and 5 ADA group patients. Event-free rates at 5 years
after biologic introduction were 62% in the IFX and 61% in the ADA group.
Patients achieving clinical remission 1 year after biologic introduction
accounted for 69% of the IFX and 90% of the ADA group, while respective rates of
secondary LOR at 5 years were 32% and 26%. C-reactive protein (CRP) at biologic
introduction (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.04-2.06; P =
.02) and age at CD onset (OR, 1.1; 95% CI, 1.01-1.20; P = .03) predicted LOR. As
to IFX and ADA efficacies after 1 year of administration, there were no
significant differences in event-free rates for the 5 years after biologic
introduction or the secondary LOR rate. CRP at biologic introduction and age at
CD onset predicted LOR.
PMID- 28422862
TI - Prevalence of abnormally invasive placenta among deliveries in mainland China: A
PRISMA-compliant Systematic Review and Meta-analysis.
AB - BACKGROUND: Abnormally invasive placenta (AIP) or placenta accreta (PA) is
considered numerous adverse maternal and fetal-neonatal complications. There has
been no detailed study to characterize the prevalence of AIP among deliveries in
mainland China. OBJECTIVES: We aimed to fill this gap and obtained overall and
regional estimates of AIP prevalence via a systematic review and meta-analysis.
METHODS: This systematic review and meta-analysis was totally performed following
the Meta-analysis of Observational Studies in Epidemiology guidelines for
systematic reviews of observational studies, and the Preferred Reporting Items
for Systematic reviews and Meta-Analysis statement for reporting systematic
reviews and meta-analysis. RESULTS: A total of 23 articles (including 350,939)
were included. Most studies (22) focused on the placenta increta (PI), only 2
articles in PA, and none in placenta percreta (PP). In this meta-analysis, the
overall prevalence of AIP was 0.22% (95% confidence interval 0.18%-0.27%) in a
heterogeneous set of studies (I = 93.5%). In a subgroup, the prevalence of PA and
PI was 0.48% and 0.23%, respectively. Stratified analyses of PI found that the
prevalence was similar in North (0.23% [0.14%-0.32%]) and South (0.23% [0.15%
0.32%]), and lower in Central (0.20% [0.09-0.31%]); the inlanders (0.17% (0.12%
0.23%]) had a lower prevalence of PI than those living in coastal areas (0.24%
[0.35%-0.63%]). As time goes on, the prevalence, from 0.03% (0.02%-0.04%) in 1970
to 1979 to 0.48% (0.30%-0.66%) in 2010 to present, was higher and higher. The
different prevalence was also found in different in maternal age groups.
CONCLUSIONS: This first systematic review and meta-analysis found that the
prevalence differed among different geographic areas and maternal age groups. The
results would be useful for the design of abnormally invasive placenta planning
and implementation adequate health care systems and treatment programs in
mainland China.
PMID- 28422863
TI - Risk factors and prognosis of pulmonary embolism in patients with lung cancer.
AB - Malignant tumors are often complicated with venous thrombosis and pulmonary
embolism (PE), particularly in lung cancer. However, owing to the limited data
regarding the clinical course about PE in lung cancer patients, the aim of this
study is to analyze the risk factors and prognosis of patients with PE and lung
cancer. We performed a retrospective case-control study, the clinical data of 90
patients in the First Affiliated Hospital of People's Liberation Army General
Hospital between Jan 2010 and Jan 2015 were analyzed, including 30 lung cancer
patients with PE (PE group), 60 lung cancer patients without PE (non-PE group),
treated during the same period. Logistic regression analysis was applied to
explore risk factors of PE. Patient survival was also compared with matched
controls via a log-rank test. The multivariate analysis revealed that
adenocarcinoma, stage III to IV, high D-dimer, and low PaO2 were independent risk
factors. The survival time in patients with PE was remarkably lower than that in
patients without PE (P < .0005). Adenocarcinoma, stage III to IV, high D-dimer
and low PaO2 are important risk factors for lung cancer patients with PE. PE
suggested a poor prognosis in lung cancer patients.
PMID- 28422864
TI - Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does
affect IL-2/IFN-gamma expression of T cells in vitro?: A prospective, randomized,
double-blind study.
AB - BACKGROUND: Ketamine has been used as an analgesic adjuvant with morphine in the
treatment of refractory cancer pain recently. But both morphine and ketamine have
been reported to produce a number of immunomodulatory effects. The current study
was performed to assess whether the concentration of ketamine, as adjuvant
analgesics for patient with refractory cancer pain, was related to its effect on
T cells interleukin-2 (IL-2)/interferon-gamma (IFN-gamma) expression in vitro.
METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from venous
blood of patients with refractory cancer pain over a Ficoll-Hypaque density
gradient. T cells were isolated from by positive selection using anti-CD3 beads.
T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group),
morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1,
MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28.
Then supernatant IL-2 and IFN-gamma protein analysis, quantitative reverse
transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-gamma were
done. RESULTS: There were no significant difference of supernatant IL-2 and IFN
gamma among C group, M group, and MK1 group, but the mRNA of M group and MK1
group were decreased compared with C group (P < .05). Compared with C group, both
of the supernatant protein and the mRNA of MK5 group and MK10 group were all
significantly decreased (P < .01). Compared with M group, both of the supernatant
protein and the mRNA of MK5 group and MK10 group were all decreased (P < .05),
while supernatant IL-2 and the mRNA of MK10 group were significantly decreased (P
< .01). CONCLUSION: In conclusion, we confirmed that just as morphine, ketamine
dose-dependently suppressed IL-2 and IFN-gamma of activated T lymphocyte of
patients with refractory cancer pain in vitro, but the inhibitory action of low
dose ketamine could be neglected.
PMID- 28422865
TI - Crystalglobulinemia manifesting as chronic arthralgia and acute limb ischemia: A
clinical case report.
AB - RATIONALE: Crystalglobulinemia is a rare disease caused by monoclonal
immunoglobulins, characterized by irreversible crystallization on refrigeration.
It causes systemic symptoms including purpura, arthralgia, and vessel occlusive
conditions to be exacerbated by exposure to cold. We report a patient with
crystalglobulinemia associated with monoclonal gammopathy of undetermined
significance (MGUS) manifesting as chronic arthralgia and recurrent acute
arterial occlusion. PRESENTING CONCERNS: A 61-year-old man, who had been
diagnosed with MGUS and who had arthralgia of unknown origin, presented with
recurrent acute limb ischemia after surgical thromboembolectomy. Refrigeration of
his serum formed precipitates that looked like needle-shaped crystals. These
crystals did not dissolve with warming, which is not a characteristic of
cryoglobulins. Skin biopsy results showed crystal-liked eosinophilic bodies in
small vessels and we diagnosed crystalglobulinemia. INTERVENTION AND OUTCOMES:
Although he underwent above-knee amputation, he was treated with a bortezomib and
dexamethasone-based chemotherapeutic regimen, following lenalidomide maintenance
therapy. Finally, he achieved complete remission and serum crystalglobulins
diminished. LESSONS: Monoclonal gammopathy, previously diagnosed as MGUS, can
cause systemic symptoms and thrombotic conditions by producing pathologic
immunoglobulins, such as crystalglobulins. In such situations, MGUS, even when it
has not progressed to multiple myeloma, can be a target of aggressive
chemotherapy. Crystalglobulinemia should be considered for patients with
monoclonal gammopathy manifesting as systemic and thrombotic symptoms exacerbated
by cooling.
PMID- 28422866
TI - The use of anticoagulants for prevention and treatment of osteonecrosis of the
femoral head: A systematic review.
AB - BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive disease,
which mainly affects young adults and often necessitates total hip arthroplasty
(THA), so early interventions are critical to successfully protect hip joint from
THA. In this review, our purpose was to determine the effects of anticoagulants
for preventing and treating the primary and secondary ONFH, respectively, before
the collapse stage or before the pathology of necrosis. METHODS: We searched
PubMed, Embase, Web of Science databases for relevant studies. Any observational
or experimental studies that evaluated anticoagulants and ONFH were our goal of
searching the electric databases. RESULTS: Four studies including a total of 218
hips were identified in this review, 2 of them were prospective studies which
performed by 1 group, 1 was a retrospective study, and the last was a prospective
comparative study. CONCLUSIONS: Our findings supported that the anticoagulants
could be used for primary ONFH. However, anticoagulants cannot play a protective
role on secondary ONFH. Moreover, there were no serious adverse effects reported
in the studies after anticoagulants treatment. Nevertheless, our present study
with some limitations such as the limited sample size only provided limited
quality of evidence; confirmation from further systematic review or meta-analysis
with large-scale, well-designed randomized control trials is required.
PMID- 28422867
TI - A simple scoring algorithm predicting extended-spectrum beta-lactamase producers
in adults with community-onset monomicrobial Enterobacteriaceae bacteremia:
Matters of frequent emergency department users.
AB - The incidence of community-onset bacteremia caused by extended-spectrum-beta
lactamase (ESBL) producers is increasing. The adverse effects of ESBL production
on patient outcome have been recognized and this antimicrobial resistance has
significant implications in the delay of appropriate therapy. However, a simple
scoring algorithm that can easily, inexpensively, and accurately be applied to
clinical settings was lacking. Thus, we established a predictive scoring
algorithm for identifying patients at the risk of ESBL-producer infections among
patients with community-onset monomicrobial Enterobacteriaceae bacteremia
(CoMEB).In a retrospective cohort, multicenter study, adults with CoMEB in the
emergency department (ED) were recruited during January 2008 to December 2013.
ESBL producers were determined based on ESBL phenotype. Clinical information was
obtained from chart records.Of the total 1141 adults with CoMEB, 65 (5.7%) caused
by ESBL producers were identified. Four independent multivariate predictors of
ESBL-producer bacteremia with high odds ratios (ORs)-recent antimicrobial use
(OR, 15.29), recent invasive procedures (OR, 12.33), nursing home residents (OR,
27.77), and frequent ED user (OR, 9.98)-were each assigned +1 point to obtain the
CoMEB-ESBL score. Using the proposed scoring algorithm, a cut-off value of +2
yielded a high sensitivity (84.6%) and an acceptable specificity (92.5%); the
area under the receiver operating characteristic curve was 0.92.In conclusion,
this simple scoring algorithm can be used to identify CoMEB patients with a high
ESBL-producer infection risk. Of note, frequent ED user was firstly demonstrated
to be a crucial predictor in predicting ESBL-producer infections. ED clinicians
should consider adequate empirical therapy with coverage of these pathogens for
patients with risk factors.
PMID- 28422868
TI - Meta-analysis of possible role of cadherin gene methylation in evolution and
prognosis of hepatocellular carcinoma with a PRISMA guideline.
AB - BACKGROUND: Cadherins (CDHs) have been reported to be associated with cancer.
However, the clinical significance of CDH gene methylation in hepatocellular
carcinoma (HCC) remains unclear. METHODS: Based on the preferred reporting items
for systematic reviews and meta-analyses (PRISMA) statement criteria, available
studies were identified from online electronic database. The overall odds ratio
(OR) and the corresponding 95% confidence interval (95% CI) were calculated and
analyzed. RESULTS: A total of 29 eligible studies with 2562 HCC samples and 1685
controls were included. E-cadherin (CDH1) hypermethylation was observed to be
significantly higher in HCC than in benign, adjacent, or normal samples.
Moreover, CDH1 hypermethylation was not associated with gender, tumor grade,
clinical stage, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection in
HCC patients. H-cadherin (CDH13), protocadherin-10 (PCDH10), P-cadherin (CDH3),
and M-cadherin (CDH15) methylation may have an increased risk of HCC in fewer
than 4 studies, and methylated cadherin 8, type 2 (CDH8) and OB-cadherin (CDH11)
had a similar OR in HCC and adjacent samples. When HCC samples were compared with
normal samples, the analysis of sample type revealed a significantly higher OR in
normal blood samples than in normal tissues for hypermethylated CDH1 (50.82 vs
4.44). CONCLUSION: CDH1 hypermethylation may play a key role in the
carcinogenesis of HCC. However, CDH1 hypermethylation was not correlated with
clinicopathological features. Methylated CDH13, PCDH10, CDH3, and CDH15, but not
methylated CDH8 or CDH11, may lead to an increased risk of HCC. Hypermethylated
CDH1 may become a noninvasive blood biomarker. Further studies with more data are
necessary.
PMID- 28422869
TI - Effects of Jianpi Qingchang decoction on the quality of life of patients with
ulcerative colitis: A randomized controlled trial.
AB - This study aims to determine the effects of the Jianpi Qingchang decoction (JQD)
on the quality of life (QOL) of patients with spleen deficiency and dampness-heat
syndrome ulcerative colitis (UC).A total of 120 active UC patients with spleen
deficiency and dampness-heat syndrome were enrolled into this study. These
patients were randomly divided into 2 groups: test group and control group (n =
60, each group). Patients in the test group were treated with JQD, while patients
in control group were treated with 5-amino salicylic acid. After treatment for 8
weeks, differences in inflammatory bowel disease questionnaire (IBDQ) scores,
short form-36 health survey questionnaire (SF-36) scores, and Sutherland Disease
Activity Index (DAI) values were compared between these 2 groups to assess the
QOL of patients.Sutherland DAI scores decreased in both groups after the
treatment, but the difference was not statistically significant (P < .05).
However, the difference in bowel symptoms, systemic symptoms, total scores of the
4 IBDQ dimensions (physical function, bodily pain, vitality, and mental health),
and total scores of the SF-36 questionnaires between these 2 groups were
statistically significant (P < .05).JQD can be used as supplementary and
alternative therapy to relieve clinical symptoms in patients with mild to
moderate active UC, and consequently improve their QOL.
PMID- 28422870
TI - Case report: The first case of Achromobacter xylosoxidans-related tunnel
infection in a patient receiving peritoneal dialysis.
AB - RATIONALE: Achromobacter xylosoxidans infection is mostly reported in
immunocompromised patients. Until now, it is still rarely reported in patients
undergoing peritoneal dialysis. PATIENT CONCERNS: This is the 1st case of A
xylosoxidans infection due to tunnel infection of a Tenckhoff catheter.
DIAGNOSIS: The diagnosis was confirmed by the report of culture. INTERVENTIONS:
Risk factors for this infection in peritoneal dialysis include uremia with an
immunocompromised state, contamination due to inexperienced skills, and aqueous
environment of the dialysate. OUTCOME: We believe that finding the source of A
xylosoxidans contamination is the most important aspect of the overall treatment
of the infection. LESSONS: Environmental investigation of suspected source
contamination is warranted in those with A xylosoxidans infection. Once the
diagnosis is made, removal of the Tenckhoff catheter should not be delayed.
PMID- 28422871
TI - Ultrasound versus fluoroscopy-guided medial branch block for the treatment of
lower lumbar facet joint pain: A retrospective comparative study.
AB - The aim of this study was to compare the mid-term effects and benefits of
ultrasound (US)-guided and fluoroscopy (FL)-guided medial branch blocks (MBBs)
for chronic lower lumbar facet joint pain through pain relief, functional
improvement, and injection efficiency evaluation.Patients with chronic lumbar
facet joint pain who received US (n = 68) or FL-guided MBBs (n = 78) were
included in this retrospective study. All procedures were performed under FL or
US guidance. Complication frequency, therapeutic effects, functional improvement,
and the injection efficiency of MBBs were compared at 1, 3, and 6 months after
the last injection.Both the Oswestry Disability Index (ODI) and the verbal
numeric pain scale (VNS) improved at 1, 3, and 6 months after the last injections
in both groups. Statistical differences were not observed in ODI and VNS between
the groups (P > .05). The proportion of patients who reported successful
treatment outcomes showed no significant differences between the groups at
different time points. Logistic regression analysis showed that sex, pain
duration, injection methods, number of injections, analgesic use, and age were
not independent predictors of a successful outcome. US guidance was associated
with a significantly shorter performance time.US-guided MBBs did not show
significant differences in analgesic effect and functional improvement compared
with the FL-guided approach. Therefore, by considering our data from this
retrospective study, US-guided MBBs warrant consideration in the conservative
management of lower lumbar facet joint pain.
PMID- 28422872
TI - Effect of HSP27 and Cofilin in the injury of hypoxia/reoxygenation on hepatocyte
membrane F-actin microfilaments.
AB - Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate
the ischemia/reperfusion injury of transplanted organ. Through the study of the
molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the
mechanism of F-actin damage induced by ischemia and reperfusion was studied from
the level of cell and molecule.The hypoxic environment of cells in vitro was
simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R
group was subdivided into 3 subgroups: H/R 2, 4, and 6 h. Changes of cell shape
and the growth state, apoptosis, ultrastructural changes, and the changes in F
actin microfilament content were observed. Heat shock protein 27 (HSP27),
Cofilin, and F-actin gene and protein levels were determined by real-time
polymerase chain reaction and western blot assay, respectively.Cells showed
circular adherence growth under normal circumstances, while the spindle cells and
shedding cells were significantly increased in H/R groups. Apoptosis cells in H/R
group were increased significantly with the extension of hypoxia time. The number
of endoplasmic reticulum was decreased significantly in the H/R group, the
mitochondrion hydropic was degenerated and the glycogen was disappeared. The F
actin fibers in the H/R group were disordered, the morphology of the fibers was
obviously decreased, and the fluorescence staining decreased obviously (P < .05).
The transcription and expression levels of HSP27, Cofilin, and F-actin were
significantly lower than those in the control group (P < .05).These results
demonstrate that H/R can affect the correct assembly of F-actin microfilaments
and weakens the normal cycle of F-actin microfilaments through inhibiting the
protein expression and gene transcription of HSP27 and Cofilin in hepatocytes,
thereby changing the skeleton of F-actin microfilaments.
PMID- 28422873
TI - Clinical features of treatment-naive patients with hepatitis B virus infection: A
community-based survey from high- and intermediate-hepatitis B endemicity regions
in Southeast China.
AB - The aim of study was to investigate the clinical features of treatment-naive
patients in 2 regions with high- and intermediate-hepatitis B endemicity level in
Southeast China and provide the baseline data for monitoring health or planning
therapy.This study included 8207 cases of treatment-naive patients with hepatitis
B virus (HBV) infection from Yuhuan (YH, high-hepatitis B endemicity region) and
Shaoxing (SX, intermediate-hepatitis B endemicity region) during 2014-2015.
Clinical data were collected from the patients. Blood samples were kept for
detecting hepatitis B surface antigen, hepatitis B envelope antigen (HBeAg),
hepatitis B envelope antibody, hepatitis B surface antibody, hepatitis B core
antibody, liver function, HBV deoxyribonucleic acid, and alpha-fetoprotein. All
persons underwent B ultrasound to exclude liver cirrhosis or cancer.Of all 8207
HBsAg-positive patients, 52.9% patients were in the low-replication (LR) stage
and 30.3% in the HBeAg-negative chronic hepatitis B (ENH) stage; 8.8% cases were
in the ENH stage with elevated alanine aminotransferase (ALT). More male than
female patients were in immune clearance (IC) or ENH stages with elevated ALT
(10.4% vs 4.8%, 12.1% vs 5.3%, respectively, P < .05). The percentage of patients
in IC and immune tolerant (IT) stages declined with increasing age, whereas the
percentages of ENH with elevated ALT stage were highest in 40 to 60 years.The
percentage of patients in IT and IC stages was higher in YH than in SX (9.4% vs
3.8%, 9.9% vs 4.2%, respectively, P < .05). More patients had HBVDNA>=10 IU/mL in
YH than in SX (24.6% vs 16.0%, P < .05), and more male than female patients had
HBVDNA>=10 IU/mL(24.5% vs 17.9%, P < .05).Clinical features varied in treatment
naive patients with HBV infection between different genders and regions. More
attention should be paid to the surveillance and therapy of patients in YH
especially male patients for the prevention and prognosis of hepatitis B.
PMID- 28422874
TI - CONSORT the effect of intraoperative dexmedetomidine on hemodynamic responses
during emergence from nasotracheal intubation after oral surgery.
AB - BACKGROUND: Dexmedetomidine provides smooth emergence with reduced agitation. The
authors hypothesized low-dose dexmedetomidine infusion might contribute to
hemodynamic stability during and after nasotracheal tube extubation. METHODS:
Ninety-three adult patients scheduled for oral and maxillofacial surgery were
enrolled in this prospective study. Patients were randomly assigned to receive
normal saline (control group, n = 31), dexmedetomidine at 0.2 MUg/kg/h (DEX0.2
group, n = 31), or dexmedetomidine at 0.4 MUg/kg/h (DEX0.4 group, n = 31). Mean
arterial pressure (MAP), heart rate (HR), and response entropy (RE) and state
entropy (SE) were recorded during emergence from anesthesia. RESULTS: Extubation
times were similar in the 3 groups. Mean MAP was significantly lower at eye
opening (T3) and immediately after extubation (T4) in the DEX0.2 (P = .013 and
.003, respectively) and DEX0.4 group (P = .003 and .027, respectively) than in
the control group. At T3 and T4, mean HR was significantly higher in the control
group than in the DEX0.2 (P = .014 and .022, respectively) or DEX0.4 groups (P =
.003 and <.001, respectively). In the postanesthetic care unit, mean MAP and HR
were significantly lower in the DEX0.2 (P = .03 and .022, respectively) and
DEX0.4 groups (P = .027 and <.001, respectively) than in the control group.
CONCLUSION: Intraoperative dexmedetomidine infusion at rates of 0.2 or 0.4
MUg/kg/h during oral and maxillofacial surgery could provide stable hemodynamic
profiles during anesthetic emergence from nasotracheal intubation without
delaying extubation times.
PMID- 28422875
TI - Jagged1 modulated tumor-associated macrophage differentiation predicts poor
prognosis in patients with invasive micropapillary carcinoma of the breast.
AB - OBJECTIVES: Invasive micropapillary carcinoma of the breast (IMPC) constitutes a
unique and aggressive subtype of breast cancer. We aimed to evaluate the
prognostic significance of the Jagged1 (a ligand of the Notch pathway)
expression, and infiltration density of tumor-associated macrophages (TAMs) in
patients with IMPC. METHODS: Jagged1 expression and CD163+, CD68+ macrophage
infiltration were evaluated by immunohistochemistry in 222 tumor samples, and the
clinical significance was analyzed. mRNA level of Jagged1 was analyzed by real
time PCR in tumor tissues. RESULTS: The IMPC patients showed larger tumor size,
more lymphatic invasion, higher expression levels of estrogen receptor (ER),
increased Ki67 index, higher Jagged1 protein level, and denser infiltration of
CD163+ macrophages compared to patients with invasive breast ductal carcinoma. In
the IMPC cohort, positive Jagged1 expression was related to aggressive features
including large tumor size, lymphatic invasion, and Ki67 overexpression.
Statistical significance was found between CD163+ macrophage infiltration and
Jagged1 expression levels. Cox regression analysis revealed that ER negativity,
positive Jagged1 expression, and a high degree of CD163+ macrophage infiltration
were independent prognostic factors for disease-free survival, and positive
Jagged1 expression was an independent prognostic factor for overall survival. The
level of Jagged1 mRNA was higher in tumor tissues of patients with IMPC.
CONCLUSION: Jagged1, by modulating TAMs infiltration, is associated with a less
favorable prognosis for patients with IMPC. Our results have important
implications for therapies targeting Jagged1-Notch signaling and re-educating
TAMs polarization for patients with IMPC.
PMID- 28422876
TI - Low complication rate of elastic stable intramedullary nailing (ESIN) of
pediatric forearm fractures: A retrospective study of 202 cases.
AB - Elastic stable intramedullary nailing (ESIN) has been established as state of the
art treatment for forearm fractures in children, if operative stabilization is
required. Their use has been expanded to single bone shaft fractures, and also
more complex injuries such as Monteggia fractures or Monteggia-like lesions. A
wide range of complications has been reported in the literature, up to 70% in
certain investigations. The purpose of this study was to assess the complication
rate after ESIN treatment of forearm fractures in children and adolescents in a
representative cohort of patients from a level 1 trauma center in Germany.Between
2000 and 2015, we retrospectively analyzed all patients, up to the age of 16
years, with forearm fractures, who were operatively treated using ESIN in our
department of general and trauma surgery. The main outcome measurements were the
rates of postoperative complications after ESIN such as re-fracture, malunion,
nonunion, tendon lesion, wound infection, and limited range of motion.In all, 201
consecutive patients with 202 forearm fractures were included in this study. Age
averaged 9.7 years (range 3-16 years). Fifteen (7.4%) fractures were open.
Fractures were 82.2% diaphyseal both-bone forearm fractures. Follow-up averaged
10.2 months (range 0.7-176.3 months). Complications were 10 re-fractures, 2
malunions, 3 extensor pollicis longus tendon ruptures, 1 superficial wound
infection, and 2 limited range of motions. Fourteen (6.9%) children required a
secondary operative intervention for their complication. Time to implant removal
averaged 3.8 months (range 0.4-16.3 months).Elastic stable intramedullary nailing
is a minimally invasive and reliable technique with a low complication rate. Both
bone forearm fractures and single bone fractures, and also Monteggia and
Monteggia-equivalent fractures can be successfully treated with this method. As a
major complication, re-fractures are frequently seen, even with ESIN in situ.
PMID- 28422877
TI - Suxamethonium induces a prompt increase in the bispectral index.
AB - Upon inducting general anesthesia in the operating room, we have observed a
prompt increase in the bispectral index (BIS) after the intravenous injection of
suxamethonium. We hypothesized that the cause of this BIS increase is muscle
hyperactivity owing to fasciculation. However, no reports have been published
regarding this abrupt increase in the BIS upon the induction of general
anesthesia by suxamethonium. To investigate the degree of change in the BIS in
patients receiving anesthesia with suxamethonium, we performed a prospective
observational study of 63 participants who underwent closed reduction for nasal
bone fracture. Anesthesia was induced by the total intravenous administration of
anesthetics and 1.5 mg kg of suxamethonium was injected intravenously upon
achieving BIS between 45 and 55. Intubation was performed after fasciculation.
Electromyograms and BIS values were recorded from the induction of suxamethonium
until 15 minutes after intubation. The mean BIS values were 95.4, 48.5, and 69.3
before induction, before the intravenous injection of suxamethonium, and
immediately after fasciculation, respectively. The BIS value immediately after
fasciculation (69.3 +/- 10.6) was significantly higher than the cutoff BIS value
of 60 (P < .001). Although fasciculation after the intravenous injection of
suxamethonium resulted in the prompt increase of the BIS to values over 60, none
of the participants was awake during surgery. In conclusion, the administration
of suxamethonium resulted in the postfasciculation increase of the BIS to an
average value of 69.3 without affecting the patient's state of consciousness.
PMID- 28422878
TI - Microsurgical treatment of carotid-ophthalmic aneurysm associated with multiple
anterior and posterior circulation aneurysms: A case report.
AB - BACKGROUND: The clipping of multiple intracranial aneurysms in 1 stage is
uncommon. In this case, we report clipping of an ophthalmic aneurysm associated
with multiple anterior and posterior circulation aneurysms via the Dolenc
approach. METHODS: The main symptoms of the patient are headache, along with
nausea and vomiting. The patient's arteriogram revealed a wide-necked aneurysm of
the right ophthalmic artery, an irregular aneurysm of the anterior communicating
artery, and a basilar artery aneurysm. The surgical intervention for these
aneurysms is a challenge because of the complex anatomical relationship with the
surrounding structures. The 3 aneurysms, which were not amenable to a single
intervention, were successfully clipped in 1 incision. RESULTS: After surgery,
the patient reported feeling well. One year after surgery, the patient had no SAH
recurrence. CONCLUSIONS: Occasionally, surgical treatment was used even for
aneurysms of the carotid-ophthalmic artery with aneurysms of anterior
communicating artery and basilar artery, which are contraindicated for
interventional therapy.
PMID- 28422879
TI - The clinicopathological features of second primary cancer in patients with prior
breast cancer.
AB - Nowadays, the risk of developing second primary cancers among women diagnosed
with prior breast cancer represents a public health issue worldwide.Twenty-eight
cases of the primary breast cancer with the multiple primary cancers (MPC)
between 2008 and 2015 at our hospital were retrospectively analyzed in regards to
age of patients, family history, interval time of the 2 cancers, and survival
time of these patients.A total 28 cases were analyzed, at the mean age of 44.57
years at the diagnosis of the first primary cancer. The most common primary
cancer in these breast cancer patients was contralateral breast cancer. Of 28
patients with breast cancer, 16 developed a second malignant tumor of the
opposite breast, there were no significant difference both median age at first
breast cancer and second breast cancer (P > .05). The difference of interval time
of 2 cancers also had no statistical significance. There was no statistically
significant difference in overall survival between the bilateral primary breast
cancers (BPBC) group and the group of breast cancer patients who diagnosed with
another cancer (P > .05). If we grouped patients age of diagnosed with the first
cancer (<45, >=45 years), no statistical different between 2 groups (P > .05).
However, the survival time with positive-node patients was lower than in patients
with node-negative, the difference had a notable significant difference (P <
.01). And there are 3 cases had a positive family history for malignant tumor in
the form of first-degree relative.Multiple primary carcinoma in patients with
prior breast cancer is not the influencing factor of prognosis. It is crucial to
detect, diagnose, and treat cancers at their early stage for improving the cure
rate of cancer and the survival rate of patients.
PMID- 28422880
TI - The management and surgical intervention timing of enchondromas: A 10-year
experience.
AB - Enchondroma, reportedly the most common primary tumor of the long bones of the
hand, usually develops during the first till fourth decades of life. However,
there has no consensus been reached regarding the surgical intervention timing
for these patients. We aim to evaluate the optimal surgical intervention timing
for the patients with fractures due to enchondromas, investigate the impact of
pathological fractures on the treatment and outcomes in these patients.Medical
records and X-rays of patients treated for enchondroma of the hand from 2005 to
2015 were retrospectively reviewed. We collected 148 cases in total and 92 of
them had complete information including X-rays, medical records, and files of
follow up.There were no significant differences in terms of consolidation time
after surgery, recurrence rate, and DASH scores between the groups with and
without fractures; the treatment costs were higher in the group with fractures
than those without fractures; however, patients without fractures were able to
resume work earlier than those with fractures.The pathological fractures
associated with enchondromas have no significant impact on the treatment outcomes
compared to those with simple nonfractured enchondromas. Although the cost was
more expensive for patients treated primarily with pathological fractures due to
enchondromas, these patients could resume their work normally much earlier than
those treated by delayed surgery. Early surgical intervention is recommended for
better results and no increased risks for patients with pathological fractures
caused by enchondromas.
PMID- 28422881
TI - Comparison of effects of desflurane and sevoflurane on postoperative nausea,
vomiting, and pain in patients receiving opioid-based intravenous patient
controlled analgesia after thyroidectomy: Propensity score matching analysis.
AB - In this study, we aimed to compare the effect of desflurane and sevoflurane on
postoperative nausea and vomiting and pain in patients receiving opioid-based
intravenous patient-controlled analgesia (IV-PCA) after thyroidectomy.We reviewed
the electronic medical records of 1042 patients administered opioid-based IV-PCA
after a thyroidectomy at Chung-Ang University Hospital between January 1, 2010
and June 30, 2016. We classified the patients into 2 groups according to the
inhalation anesthetic used for anesthesia: desflurane versus sevoflurane (groups
D and S, n = 587 and 455, respectively). Then, propensity scoring was used to
select 234 matched subjects between both groups based on their confounding
factors. A propensity score matching method was used to match patients from the 2
groups in a 1:1 ratio.Before the propensity score analysis, there was no
significant difference between the 2 groups. However, after the propensity score
matching, the frequency of complete remission (CR, defined as no nausea and
vomiting) was significantly higher in group S than it was in group D. The number
of patients administered rescue antiemetics on day 0 in group S was lower than
that in group D, although it was not statistically significant.In patients
receiving opioid-based IV-PCA after thyroidectomy, sevoflurane seems to be more
beneficial in achieving CR than desflurane was. However, further randomized
controlled studies are needed to confirm this conclusion.
PMID- 28422882
TI - Hospital mortality after hip fracture surgery in relation to length of stay by
care delivery factors: A database study.
AB - Two hypotheses were offered for the effect of shorter hospital stays on mortality
after hip fracture surgery: worsening the quality of care and shifting death
occurrence to postacute settings.We tested whether the risk of hospital death
after hip fracture surgery differed across years when postoperative stays
shortened, and whether care factors moderated the association.Analysis of acute
hospital discharge abstracts for subgroups defined by hospital type, bed
capacity, surgical volume, and admission time.153,917 patients 65 years or older
surgically treated for first hip fracture.Risk of hospital death.We found a
decrease in the 30-day risk of hospital death from 7.0% (95%CI: 6.6-7.5) in 2004
to 5.4% (95%CI: 5.0-5.7) in 2012, with an adjusted odds ratio [OR] 0.71 (95%CI:
0.63-0.80). In subgroup analysis, only large community hospitals showed the
reduction of ORs by calendar year. No trend was observed in teaching and medium
community hospitals. By 2012, the risk of death in large higher volume community
hospitals was 34% lower for weekend admissions, OR = 0.66 (95%CI: 0.46-0.95) and
39% lower for weekday admissions, OR = 0.61 (95%CI: 0.40-0.91), compared to 2004.
In large lower volume community hospitals, the 2012 risk was 56% lower for
weekend admissions, OR = 0.44 (95%CI: 0.26-0.75), compared to 2004.The risk of
hospital death after hip fracture surgery decreased only in large community
hospitals, despite universal shortening of hospital stays. This supports the
concern of worsening the quality of hip fracture care due to shorter stays.
PMID- 28422883
TI - Transverse rectus abdominis myocutaneous flap for postpneumonectomy
bronchopleural fistula: A case report.
AB - RATIONALE: Numerous types of flap coverage have been reported to prevent or to
repair bronchopleural fistulas. Most of the flaps were harvested from chest area.
However, these pedicled flaps might not be optimal for the patient who has
undergone previous radiotherapy on pulmonary parenchyma because the pedicle
artery of the flap might have been injured by irradiation. Therefore, an
alternative flap outside of the chest area is necessary. PATIENT CONCERNS: A 61
year-old male was diagnosed of squamous cell carcinoma in right upper lobe lung
(cT3N2M0, stage IIIa). After completing the neoadjuvant chemoradiotherapy, he
underwent video-assisted thoracoscopic surgery with right side intrapericardial
pneumonectomy. DIAGNOSIS: Persistent air leak due to postpneumonectomy
bronchopleural fistula. INTERVENTIONS: Pedicled transverse rectus abdominis
myocutaneous (TRAM) flap was used to repair the bronchial stump. OUTCOMES: The
bronchial stump was repaired successfully, the bronchopleural fistula was
obliterated, and the patient was free from air leak after following for 12
months. LESSONS: This case demonstrated that pedicled TRAM flap is a feasible
alternative to repair bronchopleural fistula.
PMID- 28422884
TI - Posterior reversible encephalopathy syndrome in a postpartum hemorrhagic woman
without hypertension: A case report.
AB - RATIONALE: Posterior reversible encephalopathy syndrome (PRES), which diagnosis
is based on clinical symptoms and radiological features, is a neurotoxic disease
characterized by a set of clinical manifestations, such as seizure, headache,
visual, and/or consciousness disturbance. It is the first case of PRES followed
by postpartum hemorrhage (PPH) without underlying disease. PATIENT CONCERNS: A 37
year-old healthy woman had PPH after caesarean section. Six days after delivery,
headache occurred suddenly, followed by episodes of clonus seizure. DIAGNOSES:
Brain computed tomography showed ischemic stroke. However, magnetic resonance
imaging revealed characteristics consistent with PRES. INTERVENTIONS: The patient
received phenytoin for seizure control. OUTCOMES: Seizure was under good control
over the following days. Three months later, repeated magnetic resonance imaging
showed complete remission. LESSONS: PRES may be triggered by PPH and is not
necessarily secondary to typical predisposing factors such as hypertension or
pre/eclampsia. Hormone fluctuation, increased blood pressure variation, and
massive blood transfusion may be contributed to the development of PRES in our
case. Also, it is necessary to rule out those life-threatening diseases, such as
cavernoma hemorrhage, cerebral venous thrombosis, and ischemic stroke before the
diagnosis of PRES.
PMID- 28422885
TI - Cancer of unknown primary: Registered procedures compared with national
integrated cancer pathway for illuminating external validity.
AB - Cancer of unknown primary (CUP) ranges within top 10 cancers in both incidence
and mortality. As primary identification is crucial to choosing treatment,
guidelines on CUP emphasize the diagnostic strategy. Whether guidelines are
complied with, or if they are indeed helpful, is however unclear. We compared
procedures performed in suspected CUP patients with recommendations of national
guidelines to assess external validity of guidelines.The Danish National Patient
Registry (NPR) comprising population data was utilized to identify the suspected
CUP patients during 2009 to 2010 and explore exposure to procedures and patient
survival. The cohort was investigated in terms of validity of diagnosis through
cross-referencing with the Cancer Registry (CR), which served as gold standard
for cancer diagnoses and patients' cancer histories.The NPR cohort consisted of
542 patients (275 males, 264 females) of whom 210 (38.7%) had a CUP diagnosis
confirmed. Within the cohort, 347 patients (64.0%) had a registration in CR
matching with the NPR registration. Exposure to diagnostic procedures included
biopsy (n = 439, 81.0%) and image modalities (n = 532, 98.2%). Survival was poor
with 67 (12.4%) individuals alive after 4 years.The validity of a CUP diagnosis
in NPR was low when using data from CR as reference. More than half the suspected
CUP patients had a previous cancer diagnosis with CUP being the most frequent.
Patients were diagnosed in compliance with guidelines indicating high external
validity, but less than 1 quarter had their primary identified and the 1-year
survival was approximately 20%. Research is needed to develop efficacious methods
for primary detection.
PMID- 28422886
TI - Comparison of T2 and T3 sympathectomy for compensatory sweating on palmar
hyperhidrosis.
AB - BACKGROUND: An otherwise successfully performed endoscopic thoracic sympathectomy
(ETS) to treat palmar hyperhidrosis (PH) often has a serious side effect:
compensatory sweating (CS). This side effect occurs in other parts of the body to
a disturbing extent. The objective of this study is to determine whether there is
a relationship between the level of ETS performed on patients with PH, and the
occurrence and severity of postoperational CS. METHODS: Between January 2014 and
January 2015, ETS procedures were performed on 25 randomly selected consecutive
subjects (group A) at T2 level, and on another 25 subjects (group B) at T3 level,
who all felt severely handicapped due to PH. All subjects were assessed in terms
of their demographic characteristics including gender and age, as well as
postoperative complications, short-term results, side effects, recurrence of
symptoms, and long-term results. RESULTS: The symptoms disappeared in all
subjects in short-term, and no recurrence was seen in their short or long-term
follow-ups. At the end of year one, CS developed at a rate of 12% in group A and
8% in group B, particularly in their back and abdominal regions. The overall
satisfaction with the procedure in year one was 96% in group A and 100% in group
B. CONCLUSION: When an ETS performed at T2 or T3 level for PH involves only the
interruption of the sympathetic chain, with a limitation on the range of
dissection and avoidance of any damage to ganglia, sweating is stopped
completely. No recurrence of PH is encountered, and CS develops only at low rates
and severities.
PMID- 28422887
TI - Epigastric symptoms of gallbladder dyskinesia mistaken for functional dyspepsia:
Retrospective observational study.
AB - Functional dyspepsia (FD) is a constellation of epigastric symptoms originating
in the gastroduodenal region without organic and metabolic cause. However,
similar confounding symptoms can also appear in patients with gallbladder (GB)
dyskinesia. Therefore, symptoms of GB dyskinesia may be mistaken for FD. We aimed
to identify GB dyskinesia as a cause of FD symptoms compatible with the Rome IV
criteria and the need for an evaluation of GB function in patients with FD
symptoms.We investigated information of patients with FD symptoms who underwent a
quantitative Tc-diisoproyl iminodiacetic acid cholescintigraphy (DISIDA scan)
through electronic medical records, and GB dyskinesia was judged to be the cause
of the FD symptoms if the symptoms disappeared as GB function normalized on the
follow-up DISIA scan in patient with decreased GB function on the initial DISIDA
scan.A total of 275 patients underwent a DISIDA scan. Eighteen patients of them
had FD symptoms compatible with the Rome IV criteria. Three were lost after
undergoing a DISIDA scan. Eight had normal GB function, and the other 7 had
decreased GB function on the initial DISIDA scan. In 4 of the 7 patients with GB
dyskinesia, FD symptoms disappeared as GB function normalized. As a result, GB
dyskinesia was the cause of the symptoms in 4 of 18 patients with FD symptoms
compatible with the Rome IV criteria.It is necessary to evaluate GB function in
patients with refractory FD symptoms because the symptoms can be caused by GB
dyskinesia.
PMID- 28422888
TI - 18F-FDG PET/CT for detection of the primary tumor in adults with extracervical
metastases from cancer of unknown primary: A systematic review and meta-analysis.
AB - BACKGROUND: Cancer of unknown primary (CUP) is a heterogeneous group of cancers,
so called when a biopsy from a patient reveals malignancy without giving a clue
to where in the body the primary tumor is located. Whole-body 18-fluorine
fluorodeoxyglucose positron-emission-tomography/computed tomography (18F-FDG
PET/CT) is widely used for diagnosis and staging of most cancers. We hypothesized
that 18F-FDG PET/CT-especially if used early-is suitable for the detection of the
primary tumor in patients with CUP. OBJECTIVE: To assess the ability of 18F-FDG
PET/CT to detect the primary tumor in adult CUP patients. DATA SOURCES:
PubMed/Medline, Embase, and Web of Science. STUDY ELIGIBILITY CRITERIA: Studies
on CUP from extracervical metastases in which every patient had received an 18F
FDG PET/CT scan and at least one 18F-FDG PET/CT-positive finding was confirmed by
biopsy or clinical follow-up. STUDY APPRAISAL: PRISMA and QUADAS-2 were applied.
SYNTHESIS METHODS: The pooled detection rate (DR) of 18F-FDG PET/CT was assessed
with a fixed-effects model. Heterogeneity among studies was assessed with the I
squared statistic. RESULTS: A total of 2953 articles were identified from which N
= 82 were assessed by full text and N = 20, comprising 1942 adult patients, were
included in the study. Median (range) number of patients and DR was N = 72 (21
316) and 36.3% (9.8%-75.3%), respectively. Two-thirds of included studies were
retrospective, and the pooled DR was 40.93% (95% confidence interval: 38.99%
42.87%). There was large heterogeneity between studies (I-squared = 95.9%),
randomization was not applied, CUP diagnosis was not standardized, and workup (if
described) was characterized by multiple testing procedures resulting in a highly
selected, challenging patient group. CONCLUSIONS: Despite great heterogeneity in
diagnostic workup and in studies in general, an overall DR of 40.93% suggests
that upfront application of 18F-FDG PET/CT may have a role in CUP by obviating a
great many futile diagnostic procedures. To what degree 18F-FDG PET/CT used early
in the course of disease may improve the detection rate could not be deducted
from selected articles. A large, prospective, preferably randomized, study on the
potential benefit of using 18F-FDG PET/CT up front in CUP patients is warranted
to judge if and when 18F-FDG PET/CT should be applied in these patients.
PMID- 28422889
TI - An in vitro biomechanical evaluation of an expansive double-threaded bi
directional compression screw for fixation of type II odontoid process fractures:
A SQUIRE-compliant article.
AB - Odontoid process fracture accounts for 5% to 15% of all cervical spine injuries,
and the rate is higher among elderly people. The anterior cannulated screw
fixation has been widely used in odontoid process fracture, but the fixation
strength may still be limited under some circumstances. This study aims to
investigate the biomechanical fixation strength of expansive double-threaded bi
directional compression screw (EDBCS) compared with cannulated lag screw (CLS)
and improved Herbert screw (IHS) for fixation of type II odontoid process
fracture.Thirty fresh cadaveric C2 vertebrae specimens were harvested and
randomly divided into groups A, B, and C. A type II fracture model was simulated
by osteotomy. Then the specimens of the 3 groups were stabilized with a single
CLS, IHS, or EDBCS, respectively. Each specimen was tested in torsion from 0
degrees to 1.25 degrees for 75 s in each of 5 cycles clockwise and 5 cycles
anticlockwise. Shear and tensile forces were applied at the anterior-to-posterior
and proximal-to-distal directions, respectively, both to a maximum load of 45 N
and at a speed of 1 mm/min.The mean torsional stiffness was 0.309 N m/deg for IHS
and 0.389 N m/deg for EDBCS, which were significantly greater compared with CLS,
respectively (0.169 N m/deg) (P < .05 and P < .05). The mean shear stiffness for
the EDBCS was 238 N/mm, which was significantly greater than CLS (150 N/mm) and
IHS (132 N/mm) (P < .05 and P < .05). All 3 screws only partly restored tensile
stiffness, but not significantly.Fixation with the EDBCS can improve the
biomechanical strength for odontoid process fracture compared with CLS and IHS,
especially in terms of torsional and shear stiffness.
PMID- 28422890
TI - An unusual location of gouty panniculitis: A case report.
AB - RATIONALE: Gouty panniculitis, characterised by the deposition of monosodium
urate crystals in subcutaneous tissue, is a rare clinical manifestation of gout.
PATIENT CONCERNS: The case of a 67-year-old man is reported, who presented an
erythematous nodule on the upper part of the right buttock suspicious for an
abscess. This was in the context of chemotherapy for non-Hodgkin's lymphoma.
DIAGNOSES: Histopathologic examination demonstrated gouty panniculitis.
INTERVENTIONS: Because infection was suspected, an incision was performed. The
lesion was found to be densely calcified and friable, without purulent discharge.
Therefore, a surgical en-bloc resection was performed. OUTCOMES: The wound healed
slowly initially due to a combination of malnutrition, chemotherapy and
infection. A wound infection with Enterococcus faecium was treated with
antibiotic therapy (carbapenem for seven days) and local therapy. At 6-week
follow up the wound showed good granulation tissue and was healing well by
secondary intention. The patient was instructed to continue anti-hyperuricaemic
treatment. LESSONS SUBSECTIONS: In patients known to have long-standing
hyperuricaemia and gout with nonspecific subcutaneous erythematous nodules, gouty
panniculitis should be considered.
PMID- 28422892
TI - Efficacy, safety, and cost of surgical versus nonsurgical treatment for carpal
tunnel syndrome: A systematic review and meta-analysis: Retraction.
PMID- 28422891
TI - Relationship and associated mechanisms between ambulatory blood pressure and
clinic blood pressure with prevalent cardiovascular disease in diabetic
hypertensive patients.
AB - The present study was to compare the association between ambulatory blood
pressure (ABP) and clinic BP (CBP) with prevalent cardiovascular diseases (CVD);
and the underlying mechanism would also be investigated concurrently.Diabetic
hypertensive patients were enrolled and divided into 2 groups based on presence
of CVD. Twenty-four hour-ABP monitoring was performed and between-group
differences were evaluated and logistic regression analysis was conducted.A total
of 568 diabetic hypertensive patients were enrolled, and the mean age was 60.8
years, male accounted for 67.8%. Mean durations of diabetes mellitus and
hypertension were 6.1 +/- 2.7 and 5.4 +/- 3.3 years, respectively, and 20.6% had
prevalent CVD. Compared to patients without CVD, patients with CVD had
significantly higher body mass index (BMI), plasma aldosterone concentration
(PAC), and serum sodium level. No significant between-group differences in CBP
were observed. However, 24 hour-SBP, daytime-SBP and nighttime-SBP were all
significantly higher in patients with CVD compared to those without CVD. Pearson
correlation analysis showed that BMI was positively correlated with PAC and serum
sodium level. Logistic regression analyses showed that the association between
clinic SBP and DBP with CVD were progressively attenuated to nonsignificant. In
contrast, both ambulatory SBP and DBP were independently associated with CVD.
However, after being further adjusted for PAC, no significant association was
observed between ambulatory SBP and CVD.In diabetic hypertensive patients, ABP is
superior to CBP in relation to CVD. The association between ambulatory SBP and
CVD may be dependent on aldosterone excess.
PMID- 28422893
TI - Do Concussive Symptoms Really Resolve in Young Children?
AB - OBJECTIVES: To examine the frequency and nature of postconcussive symptoms (PCSs)
and behavioral outcomes in young children following mild traumatic brain injury
(mTBI) or concussion. SETTING: Emergency department. PARTICIPANTS: Children aged
2 to 12 years presenting with either a concussion or minor bodily injury
(control). OUTCOME MEASUREMENT: Parent ratings of PCS were obtained within 72
hours of injury, at 1 week, and 1, 2, and 3 months postinjury using a
comprehensive PCS checklist. Preinjury behavior was examined at baseline using
the Clinical Assessment of Behavior, which was readministered 1 and 3 months
postinjury. RESULTS: PCS burden following mTBI peaked in the acute phase
postinjury but reduced significantly from 1 week to 1 month postinjury. Parents
of children with mTBI reported more persistent PCSs up to 3 months postinjury
than trauma controls, characterized mostly by behavioral and sleep-related
symptoms. Subtle increases in problematic behaviors were observed from baseline
(preinjury) to 1 month postinjury and persisted at 3 months postinjury; however,
scores were not classified as clinically "at risk." CONCLUSIONS: A significant
minority of young children experienced persistent PCS and problematic behavior
following mTBI. Care must be taken when assessing PCS in younger children as
method of PCS assessment may influence parental reporting.
PMID- 28422894
TI - Impact of Telephone-Based Problem-Solving Treatment on the Use of Medical and
Psychological Services in the Military.
AB - OBJECTIVE: To explore the impact of problem-solving treatment (PST) for mild
traumatic brain injury in active duty service members on the use of medical and
psychological services. PARTICIPANTS: Service members who had a mild traumatic
brain injury during their last deployment and enrolled in the CONcussion
Treatment After Combat Trauma (CONTACT) study. DESIGN: Secondary analysis of a
randomized clinical trial. Participants were assigned to telephone-based PST, or
e-mailed or mailed education only over the course of 6 months. MAIN MEASURE: Self
reported health service utilization from months 4 through 6 and 10 through 12
after initiation of treatment, using the Cornell Service Index. RESULTS: In
months 4 to 6, participants receiving PST had 6.17 times the odds of an emergency
department visit or hospitalization than those receiving education only (95%
confidence interval = 1.92-19.8; P value = .0023). These estimates, however, were
not significant using a conservative Bonferroni correction (P value threshold <
.0014). There were no other significant differences for other medical or
psychological services received in months 4 to 6 or 10 to 12. CONCLUSION:
Telephone-based PST was designed to complement clinical care, and this study
showed that it may increase emergency department utilization. Future evaluations
of PST with more accurate and complete measures of health service utilization are
needed.
PMID- 28422895
TI - Diffusion Tensor Tractography for Detection of Concomitant Traumatic Brain Injury
in Patients With Traumatic Spinal Cord Injury.
AB - OBJECTIVES: We investigated concomitant traumatic brain injury in patients with
traumatic spinal cord injury (TSCI) who had head trauma history, using diffusion
tensor tractography (DTT). DESIGN: Retrospective survey. PARTICIPANTS: We
recruited 14 consecutive patients with TSCI and coexisting head trauma history at
the time of TSCI and 30 control subjects. METHODS: The corticospinal tract (CST),
corticoreticulospinal tract (CRT), cingulum, and fornix were reconstructed using
DTT, and DTT parameters (fractional anisotropy and fiber volume) and
configuration were estimated. RESULTS: The values of fractional anisotropy and
fiber volume in the CST, CRT, cingulum, and fornix of the patient group were
significantly lower than those of the control group (P < .05). On configurational
analysis of DTT for each tract, the neural tracts for motor function (the CST and
CRT) had more injury than the neural tracts for cognitive function (the cingulum
and fornix). No association between the severity of TSCI and traumatic brain
injury was observed in terms of DTT parameters. CONCLUSIONS: Using DTT, we found
injury of the neural tracts in patients with head trauma history at the time of
TSCI. Our results suggest that brain evaluation using DTT can be recommended for
the patients with head trauma history at the time of TSCI irrespective of the
results of conventional brain MRI.
PMID- 28422896
TI - Predictors of Sleep Outcomes Following Mild Traumatic Brain Injury in
Preschoolers: Subjective and Objective Assessment of Outcome.
AB - OBJECTIVES: To investigate sleep and its predictors in preschoolers with mild
traumatic brain injury (mTBI). PARTICIPANTS AND PROCEDURE: The sample included
225 children, aged 18 to 60 months, divided into 3 groups: children with
accidental mTBI (n = 85), children with orthopedic injury (n = 58), and typically
developing children (n = 82). Retrospective reports of preinjury sleep and family
functioning were obtained as part of a baseline assessment at the time of
recruitment. Parental ratings of sleep problems were collected 6 months
postinjury on the full sample, and actigraphy data were collected on a subset of
children. Demographic, preinjury, and periinjury factors were examined as
potential predictors of sleep outcomes. RESULTS: No group differences were found
in ratings of sleep problems or for nighttime sleep duration and sleep
efficiency, as measured by actigraphy. Besides, preexisting sleep disturbances
and brain injury resulting in alteration of consciousness were identified as
predictors of poorer sleep in the mTBI group. CONCLUSION: Although mTBI did not
result in group-level sleep disturbances 6 months postinjury, the findings
suggest that premorbid and injury-related factors place some children at risk for
poorer sleep after mTBI. These factors should be documented so clinicians can
intervene early.
PMID- 28422897
TI - Outcomes Associated With Blast Versus Nonblast-Related Traumatic Brain Injury in
US Military Service Members and Veterans: A Systematic Review.
AB - OBJECTIVES: To systematically review the literature on comparative clinical and
functional outcomes following blast-related versus nonblast-related traumatic
brain injury (TBI) among US service members and Veterans. DESIGN: MEDLINE search
(January 2001 to June 2016) supplemented with hand search of reference lists and
input from peer reviewers. RESULTS: Thirty-one studies (in 33 articles) reported
on health outcomes; only 2 were rated low risk of bias. There was variation in
outcomes reported and methods of assessment. Blast and nonblast TBI groups had
similar rates of depression, sleep disorders, alcohol misuse, vision loss,
vestibular dysfunction, and functional status. Comparative outcomes were
inconsistent with regard to posttraumatic stress disorder diagnosis or symptoms,
headache, hearing loss, and neurocognitive function. Mortality, burn, limb loss,
and quality of life were each reported in few studies, most with small sample
sizes. Only 4 studies reported outcomes by blast injury mechanism. CONCLUSIONS:
Most clinical and functional outcomes appeared comparable in military service
members and Veterans with TBI, regardless of blast exposure. Inconsistent
findings and limited outcomes reporting indicate that more research is needed to
determine whether there is a distinct pattern of impairments and comorbidities
associated with blast-related TBI.
PMID- 28422898
TI - Internet and Social Media Use After Traumatic Brain Injury: A Traumatic Brain
Injury Model Systems Study.
AB - OBJECTIVES: To characterize Internet and social media use among adults with
moderate to severe traumatic brain injury (TBI) and to compare demographic and
socioeconomic factors associated with Internet use between those with and without
TBI. SETTING: Ten Traumatic Brain Injury Model Systems centers. PARTICIPANTS:
Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems
National Database and eligible for follow-up from April 1, 2014, to March 31,
2015. DESIGN: Prospective cross-sectional observational cohort study. MAIN
MEASURES: Internet usage survey. RESULTS: The proportion of Internet users with
TBI was high (74%) but significantly lower than those in the general population
(84%). Smartphones were the most prevalent means of Internet access for persons
with TBI. The majority of Internet users with TBI had a profile account on a
social networking site (79%), with more than half of the sample reporting
multiplatform use of 2 or more social networking sites. CONCLUSION: Despite the
prevalence of Internet use among persons with TBI, technological disparities
remain in comparison with the general population. The extent of social media use
among persons with TBI demonstrates the potential of these platforms for social
engagement and other purposes. However, further research examining the quality of
online activities and identifying potential risk factors of problematic use is
recommended.
PMID- 28422899
TI - Variation in Adult Traumatic Brain Injury Outcomes in the United States.
AB - OBJECTIVE: To ascertain the degree of variation, by state of acute care
hospitalization, in outcomes associated with traumatic brain injury (TBI) in an
adult population. SETTING: All acute care hospitals in 21 states in the United
States in the year 2010. PARTICIPANTS: Adult (> 18 years) patients (N = 95 546)
admitted to a hospital with a moderate or severe TBI. DESIGN: Retrospective
cohort study using data from State Inpatient Databases from Agency for Healthcare
Research and Quality's Healthcare Cost and Utilization Project. MAIN MEASURES:
Inpatient mortality and discharge to inpatient rehabilitation. RESULTS: The
adjusted risk of inpatient mortality varied between states by as much as 40%,
with age, severity of injury, and insurance status as significant factors in both
outcomes. The adjusted risk of discharge to inpatient rehabilitation varied
between by more than 100% among the states measured. CONCLUSIONS: There was
clinically significant variation between states in inpatient mortality and
rehabilitation discharge after adjusting for variables known to affect each
outcome. Future efforts should be focused on identifying the causes of this state
to-state variation, how these causes affect patient outcomes, and may serve as a
guide to further standardization of treatment for traumatic brain injury across
the United States.
PMID- 28422900
TI - The Association Between Posttraumatic Stress Disorder and Perceptions of
Deployment-Related Injury in Veterans With and Without Mild Traumatic Brain
Injury.
AB - OBJECTIVES: To examine whether the association between posttraumatic stress
disorder (PTSD) and injury perceptions (ie, consequences, emotional
representations, and coherence) differs for Veterans with mild traumatic brain
injury (mTBI) compared with Veterans with non-TBI (ie, orthopedic). PARTICIPANTS:
Eighty Veterans injured during post-9/11 deployments. DESIGN: Observational, 2*2
factorial design. MAIN MEASURES: Injury histories ascertained using the Ohio
State University TBI-Identification Method and Deployment Injury Questionnaire;
Injury Perception Questionnaire-Revised (injury perceptions); Structured Clinical
Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition (PTSD diagnosis); and PTSD Symptom Checklist-Civilian Version (PTSD
symptoms). RESULTS: The association between PTSD diagnosis and injury perceptions
did not differ between Veterans with mTBI and those with non-TBIs, adjusting for
age, subjective pain, and depressive symptoms. PTSD symptom severity was
significantly associated with injury consequences (P < .0001) and emotional
representations (P < .0001), irrespective of injury type (mTBI vs non-TBI). Only
injury coherence was associated with a significant interaction between PTSD
symptom severity and mTBI (P = .04). CONCLUSION: PTSD symptom severity influences
perceptions about mTBI and non-TBIs sustained during deployment. Altering injury
perceptions may be an important treatment target for Veterans with co-occurring
PTSD and deployment-related injuries.
PMID- 28422901
TI - The Deployment Trauma Phenotype and Employment Status in Veterans of the Wars in
Iraq and Afghanistan.
AB - OBJECTIVES: To determine the prevalence of comorbid mild traumatic brain injury
(mTBI), posttraumatic stress disorder (PTSD), and depression, termed the
deployment trauma phenotype (DTP), and its constituent diagnoses' impact on
unemployment status in a national cohort of veterans. SETTING: Retrospective
analysis of the comprehensive TBI evaluation, a Veterans Affairs-wide protocol
for assessing TBI, employment status, and psychiatric impressions. PARTICIPANTS:
The final data set consisted of 48 821 veterans. MAIN OUTCOMES AND MEASURES:
Frequency of mTBI, PTSD, and depression in isolation and combinations and their
association with unemployment status. RESULTS: Age- and education-adjusted risk
ratios (RRs) showed that the mTBI-only group was the least likely to be
unemployed, RR = 0.65 (0.59-0.71). By contrast, the greatest likelihood of
unemployment was associated with membership in the DTP group, RR = 1.45 (1.36
1.56), and the comorbid PTSD and depression group, RR = 1.39 (1.27-1.52).
Furthermore, the DTP was nearly 3 times more prevalent (16.4%) in this sample
compared with comorbid PTSD and depression (5.7%), indicating that the DTP
conveys risk for unemployment to a significantly greater number of individuals.
CONCLUSIONS AND RELEVANCE: The comorbid and interactive conditions of PTSD,
depression, and mTBI, rather than mTBI in isolation, were linked to significant
risk for unemployment in this veteran cohort. These findings suggest that
multifaceted assessments and interventions to improve postdeployment
reintegration are needed.
PMID- 28422903
TI - Pirates and Predators.
PMID- 28422902
TI - Evaluation of the Osteoinductive Effect of PDGF-BB Associated With Different
Carriers in Bone Regeneration in Bone Surgical Defects in Rats.
AB - PURPOSE: Extensive bone defects in maxillofacial region can be corrected with
autograft. However the disadvantages of this type of therapy lead to the search
for new bone substitutes. Thus, we evaluated the biological behavior and
osteoinductive platelet-derived growth factor type BB (PDGF-BB) associated with
different carriers, by histological analysis and immunohistochemical histometric
critical defects performed in rat calvaria. MATERIALS AND METHODS: Critical
defects were created with 5-mm diameter calvaria of rats. Each defect was
randomly divided into 8 experimental groups, evaluated at 15 and 30 postoperative
days for histomorphometry and immunohistochemistry. RESULTS: The results showed
new bone formation in all groups, independent of postoperative time. At 30 days,
the beta-tricalcium phosphate matrix (TCP) group just did not differ from bone
matrix mineralized bovine (BIO) group in the new bone formation (P = 0.1403). In
none of the groups' analyzed biomaterials, growth factor stimulated increase in
bone formation (P > 0.05). CONCLUSION: With the methodology used, the growth
factor associated with the tested biomaterials did not induce new bone formation.
PMID- 28422904
TI - A comparison of prognosis calculators for geriatric trauma: A Prognostic
Assessment of Life and Limitations After Trauma in the Elderly consortium study.
AB - BACKGROUND: The nine-center Prognostic Assessment of Life and Limitations After
Trauma in the Elderly consortium has validated the Geriatric Trauma Outcome Score
(GTOS) as a prognosis calculator for injured elders. We compared GTOS'
performance to that of the Trauma Injury Severity Score (TRISS) in a multicenter
sample. METHODS: Three Prognostic Assessment of Life and Limitations After Trauma
in the Elderly centers not submitting subjects to the GTOS validation study
identified subjects aged 65 years to 102 years admitted from 2000 to 2013. GTOS
was specified using the formula [GTOS = age + (Injury Severity Score [ISS] * 2.5)
+ 22 (if transfused packed red cells (PRC) at 24 hours)]. TRISS uses the Revised
Trauma Score (RTS), dichotomizes age (<55 years = 0 and >=55 years = 1), and was
specified using the updated 1995 beta coefficients. TRISS Penetrating was
specified as [TRISSP = -2.5355 + (0.9934 * RTS) + (-0.0651 * ISS) + (-1.1360 *
Age)]. TRISS Blunt was specified as [TRISSB = -0.4499 + (0.8085 * RTS Total) + (
0.0835 * ISS) + (-1.7430 * Age)]. Each then became the sole predictor in a
separate logistic regression model to estimate probability of mortality. Model
performances were evaluated using misclassification rate, Brier score, and area
under the curve. RESULTS: Demographics (mean + SD) of subjects with complete data
(N = 10,894) were age, 78.3 years +/- 8.1 years; ISS, 10.9 +/- 8.4; RTS = 7.5 +/-
1.1; mortality = 6.9%; blunt mechanism = 98.6%; 3.1 % of subjects received PRCs.
The penetrating trauma subsample (n = 150) had a higher mortality rate of 20.0%.
The misclassification rates for the models were GTOS, 0.065; TRISSB, 0.051; and
TRISSP, 0.120. Brier scores were GTOS, 0.052; TRISSB, 0.041; and TRISSP, 0.084.
The area under the curves were GTOS, 0.844; TRISSB, 0.889; and TRISSP, 0.897.
CONCLUSION: GTOS and TRISS function similarly and accurately in predicting
probability of death for injured elders. GTOS has the advantages of a single
formula, fewer variables, and no reliance on data collected in the emergency room
or by other observers. LEVEL OF EVIDENCE: Prognostic, level II.
PMID- 28422905
TI - Distance matters: Effect of geographic trauma system resource organization on
fatal motor vehicle collisions.
AB - BACKGROUND: Trauma systems improve outcome; however, it is unclear how geographic
organization of trauma system resources (TSR) affects outcome. Our objective was
to evaluate the relationship of fatal motor vehicle collision (MVC) rates and the
distance from individual MVC locations to the nearest TSR as a measure of the
geographical organization of trauma systems, as well as how theoretical changes
in the distribution of TSR may affect fatal MVC rates. METHODS: All fatal MVC in
Pennsylvania 2013-2014 were mapped from the Fatality Analysis Reporting System
database. Deaths on scene were excluded. TSR including trauma centers and
helicopter bases were mapped. Distance between each fatal MVC and nearest TSR was
calculated. The primary outcome was fatal MVC rate per 100 million vehicle miles
traveled (VMT). Empiric Bayes kriging and hot spot analysis were performed to
evaluate geographic patterns in fatal MVC rates. Association between fatal MVC
rate and distance to the nearest TSR was evaluated with linear regression.
Spatial lag regression evaluated this association while controlling for MVC and
county-level characteristics. RESULTS: We identified 886 fatalities from 863
fatal MVC. Median fatal MVC rate was 0.187 per 100 million VMT. Higher fatal MVC
rates and fatality hot spots occur in locations farther from TSR. The fatal MVC
rate increased 0.141 per 100 million VMT for every 10 miles farther from the
nearest TSR (p < 0.01). When controlling for confounders, the fatal MVC rate
increased by 0.089 per 100 million VMT for every 10 miles farther from the
nearest TSR (p < 0.01). If two helicopters stationed at trauma centers were
relocated into the highest fatality regions, our model predicts a 12.3% relative
reduction in the overall MVC fatality rate. CONCLUSIONS: Increasing distance to
the nearest TSR is associated with increasing fatal MVC rate. The geographic
organization of trauma systems may impact outcome, and geospatial analysis can
allow data-driven changes to potentially improve outcome. LEVEL OF EVIDENCE:
Prognostic/Epidemiologic, level III; Case management, level III.
PMID- 28422906
TI - Risk factors and costs associated with nationwide nonelective readmission after
trauma.
AB - BACKGROUND: Most prior studies of readmission after trauma have been limited to
single institutions, whereas multi-institutional studies have been limited to
single states and an inability to distinguish between elective and nonelective
readmissions. The purpose of this study was to identify the risk factors and
costs associated with nonelective readmission after trauma across the United
States. METHODS: The Nationwide Readmission Database was queried for all patients
with nonelective admissions in 2013 and 2014 with a primary diagnosis of trauma.
Univariate and multivariate logistic regression identified risk factors for 30
day nonelective same- and different-hospital readmission. The diagnosis groups on
readmission were evaluated, and the total cost of readmissions was calculated.
RESULTS: There were 1,180,144 patients admitted for trauma, the 30-day
readmission rate was 9.4%, and 26.4% of readmissions occurred at a different
hospital. The median readmission cost for patients readmitted to the same
hospital was $8,298 (interquartile range, $4,899-$14,911), whereas the median
readmission cost for patients readmitted to a different hospital was $8,568
(interquartile range, $4,935-$16,078; p < 0.01). Multivariate regression revealed
that patients discharged against medical advice were at increased risk of
readmission (odds ratio, 2.79; p < 0.01) and readmission to a different facility
(odds ratio, 1.58; p < 0.01). Home health care was associated with a decreased
risk of readmission to a different hospital (odds ratio, 0.74; p < 0.01).
Septicemia and disseminated infections were the most common diagnoses on
readmission (8.4%) and readmission to a different hospital (8.6%). CONCLUSIONS: A
significant portion of US readmissions occur at different hospitals with
implications for continuity of care, quality metrics, cost, and resource
allocation. Home health care reduces the likelihood of nonelective readmission to
a different hospital. Infection was the most common reason for readmission, with
ramifications for outcomes research and quality improvement. LEVEL OF EVIDENCE:
Care management/epidimeological, level IV.
PMID- 28422907
TI - Adequacy and accuracy of nontrauma center computed tomography: What are we
missing?
AB - BACKGROUND: Timely and appropriate use of computed tomography (CT) scans is
critical to the evaluation of traumatic injuries. The objective of this study was
to assess the adequacy of CT scans performed at nontrauma centers (NTCs) as they
pertain to the management of trauma patients. METHODS: Adult patients transferred
to our ACS-verified Level I trauma center from any NTC between May and December
2012 were enrolled prospectively. Available CT images from NTCs were reviewed in
a blinded fashion by our facility's trauma radiologist; his interpretations were
compared with those from the NTC. Interpretations of the trauma centers (TCs)
images were compared with the NTC interpretations. Means and proportions were
used to summarize the data. RESULTS: A total of 235 consecutive patients with a
complete dataset were included, of which, 203 (86.4%) had a CT scan performed at
an NTC. Additional imaging was obtained at the TC in 76% of patients with outside
CT (154 of 203), with inadequacy of outside CTs for patient workup based on
mechanism of injury (76%) and technical inadequacy of outside images (31%) being
the main, nonexclusive reasons to repeat imaging. Image interpretation by the
trauma radiologist at the TC using NTC images identified missed injuries in 49%
of the patients, and 90% of these missed injuries were deemed clinically
significant, meaning the injury would have altered patient care had they been
identified. When the same body region was imaged at the TC, 54% had missed
injuries, of which 76% were deemed significant. CONCLUSION: This study
demonstrates inaccuracy in the interpretation of NTC images, which can lead to
inappropriate management of trauma patients. Parameters other than imaging need
to be used to identify patients requiring a higher level of care. LEVEL OF
EVIDENCE: Therapeutic and care management study, level V.
PMID- 28422908
TI - The Emergency Surgery Score (ESS) accurately predicts the occurrence of
postoperative complications in emergency surgery patients.
AB - BACKGROUND: The Emergency Surgery Score (ESS) was recently validated as a scoring
system to predict mortality in emergency surgery (ES) patients. We sought to
examine the ability of ESS to predict the occurrence of 30-day postoperative
complications in ES. METHODS: The 2011-2012 American College of Surgeons National
Surgical Quality Improvement Program (ACS-NSQIP) database was screened for all
surgical operations classified as "emergent." Thirty-day postoperative
complications were defined as per ACS-NSQIP (e.g., surgical site infection,
respiratory failure, acute renal failure). Each patient-related ESS was
calculated, and the correlation between ESS and the probability of occurrence of
30-day postoperative complications was assessed by calculating the c-statistic.
Univariate and multivariable models were also created to identify which ESS
components independently predict complications. RESULTS: Of 37,999 cases that
captured all ESS variables, 14,446 (38%) resulted in at least one 30-day
complication. The observed probability of a 30-day complication gradually
increased from 7% to 53% to 91% at scores of 0, 7, and 15, respectively, with a c
statistic of 0.78. For ESS >15, the complication rate plateaued at a mean of 92%.
On multivariable analyses, each of the 22 ESS components independently predicted
the occurrence of postoperative complications. CONCLUSIONS: ESS reliably predicts
postoperative complications in ES patients. Such a score could prove useful for
(1) perioperative patient and family counseling and (2) benchmarking the quality
of ES care. LEVEL OF EVIDENCE: Prognostic, level III.
PMID- 28422909
TI - Multi-institutional, prospective, observational study comparing the Gastrografin
challenge versus standard treatment in adhesive small bowel obstruction.
AB - INTRODUCTION: Existing trials studying the use of Gastrografin for management of
adhesive small bowel obstruction (SBO) are limited by methodological flaws and
small sample sizes. We compared institutional protocols with and without
Gastrografin (GG), hypothesizing that a SBO management protocol utilizing GG is
associated with lesser rates of exploration, shorter length of stay, and fewer
complications. METHODS: A multi-institutional, prospective, observational study
was performed on patients appropriate for GG with adhesive SBO. Exclusion
criteria were internal/external hernia, signs of strangulation, history of
abdominal/pelvic malignancy, or exploration within the past 6 weeks. Patients
receiving GG were compared to patients receiving standard care without GG.
RESULTS: Overall, 316 patients were included (58 +/- 18 years; 53% male). There
were 173 (55%) patients in the GG group (of whom 118 [75%] successfully passed)
and 143 patients in the non-GG group. There were no differences in duration of
obstipation (1.6 vs. 1.9 days, p = 0.77) or small bowel feces sign (32.9% vs.
25.0%, p = 0.14). Fewer patients in the GG protocol cohort had mesenteric edema
on CT (16.3% vs. 29.9%; p = 0.009). There was a lower rate of bowel resection
(6.9% vs. 21.0%, p < 0.001) and exploration rate in the GG group (20.8% vs.
44.1%, p < 0.0001). GG patients had a shorter duration of hospital stay (4 IQR 2
7 vs. 5 days IQR 2-12; p = 0.036) and a similar rate of complications (12.5% vs.
17.9%; p = 0.20). Multivariable analysis revealed that GG was independently
associated with successful nonoperative management. CONCLUSION: Patients
receiving Gastrografin for adhesive SBO had lower rates of exploration and
shorter hospital length of stay compared to patients who did not receive GG.
Adequately powered and well-designed randomized trials are required to confirm
these findings and establish causality. LEVEL OF EVIDENCE: Therapeutic, level
III.
PMID- 28422911
TI - Do vented chest seals differ in efficacy? An experimental evaluation using a
swine hemopneumothorax model.
AB - OBJECTIVE: Airways compromise was the second leading cause of potentially
preventable death among combat casualties. We investigated the ability of five
Food and Drug Administration-approved nonocclusive chest seals (CSs) to seal a
bleeding chest wound and prevent tension hemopneumothorax (HPTX) in a swine
model. METHODS: Following instrumentation, an open chest wound was created in the
left thorax of spontaneously air-breathing anesthetized pigs (n = 26; 43 kg).
Autologous fresh blood (226 mL) was then infused into the pleural cavity to
produce HPTX. The chest wounds were then sealed with CSs. The sealant strength
and venting function of CSs were challenged by infusion of 50 mL more blood
directly into the chest wound and incremental air injections into the pleural
cavity. Tension HPTX was defined as intrapleural (IP) pressure equal to or more
than +1 mm Hg and more than 20% deviation in physiologic measurements. RESULTS:
An open chest wound with HPTX raised IP pressure (~ -0.7 mm Hg) and caused
labored breathing and reductions in PaO2 and SvO2 (p < 0.01). Sealing the wounds
with the CSs restored IP pressure, and improved breathing and oxygenation.
Subsequent blood infusion into the wound and IP air injections produced CS
dependent responses. Chest seals with one-way valves (Bolin and SAM) did not
evacuate the blood efficiently; pooled blood either detached the CSs from skin
and leaked out (75%), or clotted and clogged the valve and led to tension HPTX
(25%). Conversely, CSs with laminar venting channels allowed escape of blood and
air from the pleural cavity and maintained IP pressure and oxygenation near
normal levels. Success rates were 100% for Sentinel and Russell (6/6); 67% for
HyFin (4/6); 25% for SAM (1/4); and 0% for Bolin (0/4) CSs (p = 0.002).
CONCLUSION: The sealant and valve function of vented CS differed widely in the
presence of bleeding chest wounds. Medics should be equipped with more effective
CSs for treating HPTX in the field.
PMID- 28422913
TI - Confessions of a Dinosaur.
PMID- 28422912
TI - Vascular complications from resuscitative endovascular balloon occlusion of the
aorta: Life over limb?
AB - BACKGROUND: Vascular complications from resuscitative endovascular balloon
occlusion of the aorta (REBOA) have been reported in as high as 13% with some
patients requiring lower-extremity amputation. We sought to review our
institution series of REBOA and assess our vascular complications. METHODS:
Retrospective review of all patients undergoing REBOA from October 2011 through
July 2016. Data were gathered from the Memorial Hermann Trauma Registry and the
hospital electronic medical records. Operative details and vascular injuries from
arterial access for REBOA insertion were recorded. RESULTS: Forty-eight patients
underwent REBOA during our study period. Thirty-eight had the 14 Fr. system
placed and 10 had the 7 Fr. system placed. Of the 24 surviving the removal of the
14 Fr. sheath, 19 had primary repair of the arteriotomy without vascular
complication. The other five required additional vascular procedures to repair
arteriotomy with no lower-extremity amputations. There were no vascular
complications of sheath removal with the 7 Fr. system, with no amputations.
CONCLUSION: Implementation of REBOA can be done safely without increased risk of
vascular access complications or limb loss. The 14 Fr. system will more likely
require further vascular procedures to address the access site, whereas the 7 Fr.
system will not. LEVEL OF EVIDENCE: Therapeutic/care management, level II.
PMID- 28422914
TI - Delays to the operating room increase mortality in sick trauma patients.
PMID- 28422915
TI - Enteral tranexamic acid attenuates vasopressor resistance and changes in alpha1
adrenergic receptor expression in hemorrhagic shock.
AB - BACKGROUND: Irreversible hemorrhagic shock is characterized by hyporesponsiveness
to vasopressor and fluid therapy. Little is known, however, about the mechanisms
that contribute to this phenomenon. Previous studies have shown that decreased
intestinal perfusion in hemorrhagic shock leads to proteolytically mediated
increases in gut permeability, with subsequent egress of vasoactive substances
systemically. Maintenance of blood pressure is achieved in part by alpha1
receptor modulation, which may be affected by vasoactive factors; we thus
hypothesized that decreases in hemodynamic stability and vasopressor response in
shock can be prevented by enteral protease inhibition. METHODS: Rats were exposed
to experimental hemorrhagic shock (35 mm Hg mean arterial blood pressure for 2
hours, followed by reperfusion for 2 hours) and challenged with phenylephrine (2
MUg/kg) at discrete intervals to measure vasopressor responsiveness. A second
group of animals received enteral injections with the protease inhibitor
tranexamic acid (TXA) (127 mM) along the small intestine and cecum 1 hour after
induction of hemorrhagic shock. RESULTS: Blood pressure response (duration and
amplitude) to phenylephrine after reperfusion was significantly attenuated in
animals subjected to hemorrhagic shock compared with baseline and control
nonshocked animals and was restored to near baseline by enteral TXA. Arteries
from shocked animals also displayed decreased alpha1 receptor density with
restoration to baseline after enteral TXA treatment. In vitro, rat shock plasma
decreased alpha1 receptor density in smooth muscle cells, which was also
abrogated by enteral TXA treatment. CONCLUSION: Results from this study
demonstrate that experimental hemorrhagic shock leads to decreased response to
the alpha1-selective agonist phenylephrine and decreased alpha1 receptor density
via circulating shock factors. These changes are mitigated by enteral TXA with
correspondingly improved hemodynamics. Proteolytic inhibition in the lumen of the
small intestine improves hemodynamics in hemorrhagic shock, possibly by restoring
alpha1 adrenergic functionality necessary to maintain systemic blood pressure and
perfusion.
PMID- 28422916
TI - Beware of the interval cholecystectomy.
AB - BACKGROUND: Despite limited data regarding the indications and effectiveness of
percutaneous cholecystostomy (PC) in the treatment of acute cholecystitis (AC),
usage has increased by over 500% since 1994. Many of these patients subsequently
undergo interval cholecystectomy (IC), a procedure that has not been rigorously
evaluated. This aim of this study was to quantify the morbidity and mortality
associated with the IC. METHODS: We included all consecutive adult patients (>18
years old) who underwent PC and IC from January 2008 to December 2013. Conversion
rate, length of operation, biliary injury, estimated blood loss, surgical site
infection, length of stay, and mortality were compared with 227 patients who
underwent cholecystectomy for AC during the same time interval. RESULTS: Of
18,501 patients who underwent cholecystectomy, 337 had at least one PC and 177
underwent subsequent IC. Compared with patients undergoing cholecystectomy for
clinically diagnosed AC, patients undergoing IC were older (69.8 vs. 54.9 years;
p < 0.001), thinner (body mass index, 28.7 vs. 31.1; p = 0.002), more complex by
Tokyo grade (1.9 vs. 1.1; p < 0.001), and American Society of Anesthesia
classification (3.0 vs. 2.5; p < 0.001), had longer operative times (120.7 vs.
92.5 minutes; p < 0.0001), more blood loss (30 vs. 15 mL; p = 0.01), and
increased rates of conversion (26.6% vs. 12.8%; p < 0.001), surgical site
infection (12.4% vs. 0.4%; p < 0.001), bowel injury (6.2% vs. 0.4%; p < 0.001),
and 1-year mortality (15.3% vs. 0.4%; p < 0.01). Nonsignificant trends included
significant biliary tract injury (3 vs. 0; p = 0.08) and longer length of stay
(7.3 vs. 4.8 days; p = 0.39). Linear regression identified body mass index (p =
0.03), time from admission to PC (p = 0.03), and American Society of Anesthesia
classification (p = 0.06) as predictors of a difficult IC. CONCLUSION: PC has
been widely adopted with limited description of the subsequent IC. Our data
detail the factors predicting the challenges of IC and document that it is a
difficult operation associated with significant morbidity. LEVEL OF EVIDENCE:
Therapeutic, level IV.
PMID- 28422918
TI - Reassessing the cardiac box: A comprehensive evaluation of the relationship
between thoracic gunshot wounds and cardiac injury.
AB - BACKGROUND: High-energy missiles can cause cardiac injury regardless of entrance
site. This study assesses the adequacy of the anatomic borders of the current
"cardiac box" to predict cardiac injury. METHODS: Retrospective autopsy review
was performed to identify patients with penetrating torso gunshot wounds (GSWs)
2011 to 2013. Using a circumferential grid system around the thorax, logistic
regression analysis was performed to detect differences in rates of cardiac
injury from entrance/exit wounds in the "cardiac box" versus the same for
entrance/exit wounds outside the box. Analysis was repeated to identify regions
to compare risk of cardiac injury between the current cardiac box and other
regions of the thorax. RESULTS: Over the study period, 263 patients (89% men;
mean age, 34 years; median injuries/person, 2) sustained 735 wounds (80% GSWs),
and 239 patients with 620 GSWs were identified for study. Of these, 95 (34%)
injured the heart. Of the 257 GSWs entering the cardiac box, 31% caused cardiac
injury, whereas 21% GSWs outside the cardiac box (n = 67) penetrated the heart,
suggesting that the current "cardiac box" is a poor predictor of cardiac injury
relative to the thoracic non-"cardiac box" regions (relative risk [RR], 0.96; p =
0.82). The regions from the anterior to posterior midline of the left thorax
provided the highest positive predictive value (41%) with high sensitivity (90%)
while minimizing false-positives, making this region the most statistically
significant discriminator of cardiac injury (RR, 2.9; p = 0.01). CONCLUSION: For
GSWs, the current cardiac box is inadequate to discriminate whether a GSW will
cause a cardiac injury. As expected, entrance wounds nearest to the heart are the
most likely to result in cardiac injury, but, from a clinical standpoint, it is
best to think outside the "box" for GSWs to the thorax. LEVEL OF EVIDENCE:
Therapeutic/care management, level IV.
PMID- 28422920
TI - A multiyear assessment of a hospital-school program to promote teen motor vehicle
safety.
AB - BACKGROUND: Motor vehicle crashes are the leading cause of death among teen
drivers. The main goal of this program was to reduce texting while driving among
high school teens through a unique peer-generated anti-texting campaign. METHODS:
The program consisted of two phases. In phase 1, student leaders participated in
a half-day, hospital-based experiential program that emphasized safe teen
driving. In phase 2, these students conceptualized and implemented an anti
texting while driving campaign during the school year. The program enrolled 32
schools with 137 student participants in phase 1.This study uses a prospective
quasi-experimental pre-post design. A presurvey and a follow-up online survey
were used. Response rate was 81%. In phase 2, two rounds of observations of
drivers were made near the participating schools at the beginning and end of the
phase 2 campaign. The results were analyzed using proportion tests. RESULTS:
There was a strong belief (6.49 on a seven-point scale) that texting while
driving could result in a crash. About 58% had texted while driving in the
previous 7 days in the pre-survey. This proportion decreased significantly to 44%
in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing
laws and feeling of empowerment to take action with a teen driver who was texting
improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens)
were observed in the first round, and 13,153 were observed in the second round of
observations. Significant reduction in the proportion of drivers texting while
driving (from 13% to 9%; p < 0.0001) was observed. CONCLUSION: Results of driver
observations support the effectiveness of this program in meeting the key
objective of reducing texting while driving. The program also influenced
teenagers' willingness to take positive steps when faced with a driver who was
texting. Future efforts should aim to influence social and peer norms. LEVEL OF
EVIDENCE: Therapeutic study, level III.
PMID- 28422921
TI - Population-based estimate of trauma-related deaths for law enforcement personnel:
Risks for death are higher and increasing over time.
AB - BACKGROUND: Trauma-related deaths remain an important public health problem. One
group susceptible to death due to traumatic mechanisms is US law enforcement
(LE). We hypothesized that LE officers experienced a higher chance of violent
death compared with the general US population and that risks have increased over
time. METHODS: The National Institute on Occupational Safety and Health National
Occupational Mortality Surveillance is a population-based survey of occupational
deaths. It includes data for workers who died during 1985 to 1998 in one of 30 US
states (EARLY period). Additional deaths were added from 23 US states in 1999,
2003 to 2004, 2007 to 2010 (LATE period). Mortality rates are estimated by
calculating proportionate mortality ratios (PMR). A PMR above 100 is considered
to exceed the average background risk for all occupations. All adults older than
18 years whose primary occupation was listed as "law enforcement worker" were
included in the analysis. RESULTS: Law enforcement personnel were more likely to
die from an injury compared with the general population (Fig. 1). The overall PMR
for injury in EARLY was 111 (95% confidence interval [CI], 108-114; p < 0.01),
and for LATE was 118 (95% CI, 110-127; p < 0.01). Four mechanisms of death
reached statistical significance: motor vehicle traffic (MVT)-driver, MVT-other,
intentional self-harm, and assault/homicide. The highest PMR in EARLY was
associated with firearms (PMR, 272; 95% CI, 207-350; p < 0.01). The highest PMR
in LATE was associated with death due to being a driver in an MVT (PMR, 194; 95%
CI, 169-222; p < 0.01). There were differences in risk of death by race and sex.
White females had the highest PMR due to assault and homicide (PMR, 317; 95% CI,
164-554; p < 0.01). All groups had similar risks of death due to intentional self
harm (PMR, 130-171). CONCLUSION: The risk of death for US LE officers is high and
increasing over time, suggesting an at-risk population that requires further
interventions. Targeted efforts based on risk factors, such as sex and race, may
assist with the development of prevention programs for this population. LEVEL OF
EVIDENCE: Epidemiologic study, level II.
PMID- 28422922
TI - The spatial epidemiology of pediatric trauma: A statewide assessment.
AB - BACKGROUND: Despite significant advances in the prevention and treatment of
pediatric trauma, preventable injuries continue to burden the lives of millions
of children. To target prevention strategies, it is critical to identify areas
with high burdens of pediatric trauma. Therefore, this study analyzed statewide
data from the Ohio Trauma Registry from 2007 to 2012 to identify geographical
patterns in pediatric injury. METHODS: Data from the first hospital of care for
16,330 pediatric trauma patients younger than 16 years were analyzed using the
disease mapping method adaptive spatial filtering to estimate a series of maps
that display age- and sex-adjusted rates of pediatric trauma, severe trauma, and
standardized mortality ratios while controlling for population size to create
stable estimates throughout the study area. The locations of all trauma centers
were mapped to highlight access to trauma care. RESULTS: Areas with significantly
higher than expected rates of severe injury were identified in nonurban areas,
where children lacked timely access to a pediatric trauma center or Level I adult
trauma center. Although highest standardized mortality ratios were in urban
areas, nonurban areas experienced elevated mortality with rates over four times
higher than expected. CONCLUSION: Areas with higher than expected age- and sex
adjusted rates of severe injury and mortality should be further explored to
identify opportunities for injury prevention and appropriate access to timely
care. LEVEL OF EVIDENCE: Epidemiologic study, level III.
PMID- 28422923
TI - A cross-sectional study of emergency care utilization and associated costs of
violent-related (assault) injuries in the United States.
AB - BACKGROUND: Violent-related (assault) injuries are a leading cause of death and
disability in the United States. Many violent injury victims seek treatment in
the emergency department (ED). Our objectives were to (1) estimate rates of
violent-related injuries evaluated in United States EDs, (2) estimate linear
trends in ED visits for violent-related injuries from 2000 to 2010, and (3) to
determine the associated health care and work-loss costs. METHODS: We examined
adults 18 years and older from a nationally representative survey (the National
Hospital Ambulatory Medical Care Survey) of ED visits, from 2000 to 2010. Violent
injury was defined using International Classification of Diseases-9th Rev.
Clinical Modification, diagnosis and mechanism of injury codes. We calculated
rates of ED visits for violent injuries. Medical and work-loss costs accrued by
these injuries were calculated for 2005, inflation-adjusted to 2011 dollars using
the WISQARS Cost of Injury Reports. RESULTS: An annual average of 1.4 million
adults were treated for violent injuries in EDs from 2000 to 2010, comprising
1.6% (95% confidence interval, 1.5%-1.6%) of all US adult ED visits. Young adults
(18-25 years), men, nonwhites, uninsured or publically insured patients, and
those residing in high poverty urban areas were at increased risk for ED visits
for violent injury. The 1-year, inflation-adjusted medical and work-loss cost of
violent-inflicted injuries in adults in the United States was US $49.5 billion.
CONCLUSION: Violent injuries account for over one million ED visits annually
among adults, with no change in rates over the past decade. Young black men are
at especially increased risk for ED visits for violent injuries. Overall, violent
related injuries resulted in substantial financial and societal costs. LEVEL OF
EVIDENCE: Epidemiological study, level III.
PMID- 28422924
TI - "Pay it Forward" Eastern Association for the Surgery of Trauma 2017 Presidential
Address.
PMID- 28422925
TI - Dynamics of B Cell Recovery In Kidney/Bone Marrow Transplant Recipients.
AB - BACKGROUND: Previous studies identified B cell gene signatures and predominance
of specific B cell subsets as a marker of operational tolerance after kidney
transplantation. These findings suggested a role for B cells in the establishment
or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of
whom achieved tolerance after combined kidney/bone marrow transplantation.
METHODS: Peripheral B cell subsets were examined longitudinally by flow
cytometry. Immunoglobulin heavy chain repertoire analysis was performed using
next-generation sequencing. Lastly, the patients' serum reactivity to HLA was
assessed by Luminex. RESULTS: B cell counts recovered approximately 1 year
posttransplant except for 1 subject who experienced delayed reconstitution. This
subject resumed immunosuppression for acute rejection at 10 months posttransplant
and underwent preemptive retransplantation at 3 years for chronic rejection. B
cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional
B cells and a diversified clonal repertoire. However, all 4 subjects showed
prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B
cell counts were still low and the clonal B cell repertoire very limited. The
predominance of memory B cells was also associated with high levels of
somatically mutated immunoglobulin heavy chain variable sequences and transient
serum reactivity to HLA. CONCLUSIONS: Our observations reveal the presence of
memory B cells early posttransplant that likely escaped the preparative regimen
at a time consistent with the establishment of tolerance. Further studies are
warranted to characterize the functional properties of these persisting memory
cells and evaluate their potential contribution to tolerance induction.
PMID- 28422926
TI - Targeting High Calcineurin Inhibitor Levels After Acute Rejection With Less
Tremor: A New Strategy.
PMID- 28422928
TI - Are Nurse Leaders Prepared to Lead Across the Continuum of Care in the New
Paradigm?
AB - The movement toward linking reimbursement with outcomes necessitates providing
care across a continuum of settings, leading to the need for a new healthcare
paradigm. Issues related to shifting to this new paradigm include disagreement
about what this paradigm encompasses, the fragmentation of the healthcare system,
and overreliance on the medical model as a framework for driving health policy
decisions. We advocate for nurse leaders to guide the development of this new
paradigm.
PMID- 28422927
TI - The Relationship Between Specialty Certification of Individual Nurses and
Outcomes: Developing a Standardized Taxonomy for Research.
AB - Specialty certification is an important method to demonstrate that RNs possess
advanced training, knowledge, and competencies required to provide safe, high
quality care for specific populations.
PMID- 28422929
TI - Examining the Educational Experiences and Outcomes of the American Organization
of Nurse Executives Nurse Manager Fellowship Program: A Multiclass Study.
PMID- 28422930
TI - Exploring the Best Practices of Nursing Research Councils in Magnet(r)
Organizations: Findings From a Qualitative Research Study.
AB - OBJECTIVE: The objective of this descriptive qualitative study was to identify
best practices of nursing research councils (NRCs) at Magnet(r)-designated
hospitals. BACKGROUND: Nursing research (NR) is essential, adding to the body of
nursing knowledge. Applying NR to the bedside improves care, enhances patient
safety, and is an imperative for nursing leaders. METHODS: We interviewed NR
designees at 26 Magnet-recognized hospitals about the structure and function of
their NRCs and used structural coding to identify best practices. RESULTS: Most
organizations link NR and evidence-based practice. Council membership includes
leadership and clinical nurses. Councils conduct scientific reviews for nursing
studies, supporting nurse principal investigators. Tracking and reporting of NR
vary widely and are challenging. Councils provide education, sponsor research
days, and collaborate interprofessionally, including with academic partners.
CONCLUSIONS: Findings from this study demonstrate the need to create formal
processes to track and report NR and to develop outcome-focused NR education.
PMID- 28422931
TI - Development and Psychometric Evaluation of the Professional Practice Work
Environment Inventory.
AB - OBJECTIVE: The purpose is to examine the psychometric properties of the
professional practice work environment inventory (PPWEI). BACKGROUND: Derived
from the Professional Practice Environment (PPE) and the Revised PPE scales, the
PPWEI was designed to measure 8 components of the PPE that can be used to assist
nurse administrators in decision-making. METHODS: A psychometric evaluation was
undertaken with 874 nurses who were providing direct care to patients at the
Massachusetts General Hospital and who provided no missing data on the newly
developed 72-item PPWEI. RESULTS: Cronbach's alpha internal consistency
reliability of the total score was .93, with 61 items having factor loadings more
than .50, the factor loading cutoff used to define the component subscales.
Principal component analyses with varimax rotation and Kaiser normalization
demonstrated 8 components, explaining 64.6% of variance. Cronbach's alpha
reliability coefficients of the PPWEI subscales ranged from .82 to .93.
CONCLUSION: The multidimensional PPWEI is a psychometrically sound measure of
several components of the PPE in the acute care setting and sufficiently reliable
and valid for use as independent subscales in healthcare research.
PMID- 28422932
TI - Clarifying the Conundrum: Evidence-Based Practice, Quality Improvement, or
Research?: The Clinical Scholarship Continuum.
AB - Nurses' active involvement in clinical scholarship is necessary to advance the
nursing profession and improve patient outcomes. Yet, definitional confusion and
numerous barriers exist to clinical scholarship in and across academic and
patient care settings. We discuss factors that pose barriers to the continuum of
clinical scholarship and suggest opportunities for clinician-researcher
collaborations that promote nurses' engagement in evidence-based practice,
quality improvement, and research.
PMID- 28422933
TI - Nursing Informatics Competency Assessment for the Nurse Leader: Instrument
Refinement, Validation, and Psychometric Analysis.
AB - OBJECTIVE: The aim of this article is to refine and validate a new instrument,
Nursing Informatics Competency Assessment for the Nurse Leader (NL). BACKGROUND:
Because health information technology rapidly advances, the NL requires greater
levels of informatics knowledge. METHODS: Item reduction and psychometric
analysis methodology RESULTS: A total of 357 national NLs completed the survey.
Exploratory factor analysis resulted in a final 6-factor solution that contained
26 items: (1) strategic implementation management, (2) advanced information
management and education, (3) executive planning, (4) ethical and legal concepts,
(5) information systems concepts, and (6) requirements and system selection.
Cronbach's alpha were .96, .91, .90, .83, .92, .81, respectively. CONCLUSION: We
established a valid and reliable nursing informatics competency assessment
instrument with sufficient specificity to guide NLs to recognize the competencies
required in their role, create solutions to address potential gaps, and enhance
delivery of patient care.
PMID- 28422934
TI - Impact of Professional Nursing Practices on Patient/Nurse Outcomes: Testing the
Essential Professional Nursing Practices Instrument.
AB - Increasing patient and healthcare system complexity and the need to accurately
measure the engagement of clinical nurses (CNs) in holistic, professional nursing
practice indicates that an update to the Essentials of Magnetism instrument is
needed. The purposes of this research were to critique and weight items, assess
the value and psychometric properties of the newly constructed Essential
Professional Nursing Practices (EPNP) instrument, and establish relationships
between EPNPs and CN job, practice, and nurse-assessed patient satisfaction.
PMID- 28422935
TI - The Baptist Health Nurse Retention Questionnaire: A Methodological Study, Part 1.
AB - OBJECTIVE: The purposes of this study were to develop and test the Baptist Health
Nurse Retention Questionnaire (BHNRQ) and examine the importance of nurse
retention factors. BACKGROUND: Multiple factors, including increasing patient
acuity levels, have led to concerns regarding nurse retention. An understanding
of current factors related to retention is limited. METHODS: To establish the
psychometric properties of the BHNRQ, data were collected from 279 bedside nurses
at a 391-bed, Magnet(r) redesignated community hospital. A principal component
analysis was conducted to determine the subscale structure of the BHNRQ.
Additional analyses were conducted related to content validity and test-retest
reliability. RESULTS: The results of the principal components analysis revealed 3
subscales: nursing practice, management, and staffing. Analyses demonstrate that
the BHNRQ is a reliable and valid instrument for measuring nurse retention
factors. CONCLUSION: The BHNRQ was found to be a clinically useful instrument for
measuring important factors related to nurse retention.
PMID- 28422936
TI - Phenotypic Characterization of Adherent Cells Population CD34+ CD90+ CD105+
Derived from Wharton's Jelly.
AB - BACKGROUND Mesenchymal stromal cells, MSCs, show expression of specific antigens
on their surface. The aim of the study is to assess the phenotype of stem cells
like isolated from the umbilical cord with respect to the presence of surface
antigens CD34, CD90, and CD105 and differences in the expression of surface
antigens in cells isolated from freshly sampled material in comparison with the
phenotype of cells from in vitro culture. MATERIAL AND METHODS Stem cells
collected from the umbilical cord from healthy patients and then cultured in
vitro. To assess the phenotype of stem cells, cytometric analysis was carried
out. To assess the phenotype of cells we used fluorescently labelled monoclonal
antibodies: APC Mouse anti-human CD34, PC5 Mouse anti-human CD90 and PE Mouse
anti-human CD105. RESULTS In the case of cells from the umbilical cord and then
cultured in vitro for the period of 10-14 days CD34 expression is lower (69,5%)
in comparison with the group of cells not cultured. Not cultured cells were
demonstrated 37% of cells co-expression of antigens CD34 and CD105, over 21% of
CD34/CD90 cells and over 24% of CD105/CD90. Cultured cells group was showed
higher percentage of CD90, CD105, CD34/CD105, CD34/CD90, CD105/CD90 in comparison
with not cultured cells. CONCLUSIONS Our reults suggested that adherent cells
population from umbilical cord, demonstrate CD34 expression In vivo. Moreover,
the phenotype of MSCs, mainly in the context of CD34 expression, may vary
depending on the place of collection of cells and the length of growing the cell
culture.
PMID- 28422937
TI - Let there be sight.
PMID- 28422938
TI - Corneal repair: a clear vision.
PMID- 28422939
TI - Predictive factors for achieving independent walking in children with Guillain
Barre syndrome.
AB - BackgroundTo determine the predictors of achieving independent walking at 2 and 6
months after onset of weakness in children with Guillain-Barre syndrome
(GBS).MethodsChildren with GBS admitted to the Tabriz Children's Hospital were
studied prospectively. All patients had frequent clinical evaluations until
achieving independent walking. Unaided walking at 2 and 6 months and factors
influencing these outcomes were determined using both univariate and multiple
analyses.ResultsBetween 2003 and 2014, 324 children (mean age: 5.3+/-3.66 years)
were admitted. The mean duration to independent walking was 2.97+/-3.02 months;
90.5% of patients could walk independently at 6 months. In the univariate
analysis, disability score of >3 (P=0.03), autonomic nerve involvement (P=0.003),
cranial nerve involvement (P=0.008), and absent compound muscle action potential
(CMAP; P=0.048) were found to be significantly associated with poor walking
outcome at 6 months. In the multivariate analysis, cranial nerve involvement
(P=0.008) and absence of CMAP (P=0.022) were independently associated with poor
functional outcome.ConclusionDisability score >3, cranial and autonomic nerve
involvement, and absence of CMAP were predictors of independent walking in
childhood GBS in this study; early rehabilitation program may prevent further
impairments secondary to immobility in these patients.
PMID- 28422940
TI - Body composition at birth and height at 2 years: a prospective cohort study among
children in Jimma, Ethiopia.
AB - BACKGROUNDLow birth weight is associated with childhood stunting, but equivalent
associations for birth body composition (BC) remain unknown. The aim of this
study was to assess associations between birth BC and height-for-age z-score
(HAZ) at 2 years of age.METHODSIn a prospective cohort study, fat mass (FM) and
fat-free mass (FFM) were measured using air-displacement plethysmography within
48 h of birth. Linear regression models were applied to study the relationship
between BC at birth and HAZ at 24 +/-3 months.RESULTSA total of 268 children with
height assessment at 2 years were included. Mean+/-SD HAZ at 2 years of age was
1.2+/-1.2, with 25.8% classified as stunted (HAZ <-2SD). FFM at birth was
positively associated with HAZ at 2 years, independent of length at birth. When
adjusted for potential confounders, HAZ at 2 years was 0.73 higher for each
additional kg FFM at birth (beta=0.73, 95% CI: 0.08, 1.38). FM was not associated
with HAZ at 2 years in any model.CONCLUSIONThe FFM component of birth weight,
independent of length at birth, explained variability in HAZ at 2 years. Further
studies are required to explore how changes in early infant BC are associated
with linear growth.
PMID- 28422941
TI - Metabolism-related microRNAs in maternal breast milk are influenced by premature
delivery.
AB - BackgroundMaternal breast milk (MBM) is enriched in microRNAs, factors that
regulate protein translation throughout the human body. MBM from mothers of term
and preterm infants differs in nutrient, hormone, and bioactive-factor
composition, but the microRNA differences between these groups have not been
compared. We hypothesized that gestational age at delivery influences microRNA in
MBM, particularly microRNAs involved in immunologic and metabolic
regulation.MethodsMBM from mothers of premature infants (pMBM) obtained 3-4 weeks
post delivery was compared with MBM from mothers of term infants obtained at
birth (tColostrum) and 3-4 weeks post delivery (tMBM). The microRNA profile in
lipid and skim fractions of each sample was evaluated with high-throughput
sequencing.ResultsThe expression profiles of nine microRNAs in lipid and skim
pMBM differed from those in tMBM. Gene targets of these microRNAs were
functionally related to elemental metabolism and lipid biosynthesis. The microRNA
profile of tColostrum was also distinct from that of pMBM, but it clustered
closely with tMBM. Twenty-one microRNAs correlated with gestational age
demonstrated limited relationships with method of delivery, but not other
maternal-infant factors.ConclusionPremature delivery results in a unique MBM
microRNA profile with metabolic targets. This suggests that preterm milk may have
adaptive functions for growth in premature infants.
PMID- 28422942
TI - Development of tandem mass spectrometry-based creatinine measurement using dried
blood spot for newborn mass screening.
AB - BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are the
most prevalent etiologies of pediatric chronic kidney disease (CKD). However, no
robust mass screening methods have been developed to detect patients with CAKUT,
making early intervention to prevent progressive renal failure
challenging.MethodsWe applied tandem mass spectrometry (MS/MS) to measure the
creatinine (Cr) value from dried blood spot (DBS) analysis, which has been used
for newborn mass screening. Subsequently, we evaluated the correlation between
DBS Cr measured by MS/MS and serum Cr measured by the conventional method in
pediatric patients with CKD. Finally, DBS Cr was measured in 190 full-term,
healthy newborns on days 4-6 after birth.ResultsWe established a system of MS/MS
based measurement of Cr from DBS. Measured DBS Cr in the pediatric patients
showed a strong association with serum Cr (r=0.86; P<0.01). The median DBS Cr
value in newborns was 0.222 (interquartile range: 0.189, 0.269) mg/dl. No
significant correlations were found between DBS Cr values and body weight, Apgar
score, gestational age, and sex in newborns.ConclusionWe successfully established
a method for MS/MS-based measurement of Cr for newborn screening and determined
normal reference values for full-term newborns.
PMID- 28422944
TI - Growth and development in late-preterm infants: what can public policy do?
PMID- 28422943
TI - The effect of prenatal TVOC exposure on birth and infantile weight: the Mothers
and Children's Environmental Health study.
AB - BACKGROUNDVolatile organic compounds (VOCs) might restrict prenatal and postnatal
growth. However, the effect of the exposure of prenatal VOCs on postnatal growth
has not been studied sufficiently. Thus, we investigated the relationship between
the exposure of total volatile organic compounds (TVOCs) during pregnancy and its
effects on postnatal growth.METHODSA total of 383 pregnant participants were
enrolled from 2006 to 2008. We investigated maternal characteristics using a
questionnaire. Personal air samples of TVOCs were obtained in mid or late
pregnancy. After these mothers had given birth, 360 singleton newborns were
selected and postnatal follow-up data were collected at 6, 12, 24, and 36 months,
as well as anthropometric factors including body weight. Multiple general linear
and mixed models were applied for statistical analyses.RESULTSThe mean
concentration of prenatal exposure to TVOCs was 284.2 MUg/m3 and that of
formaldehyde was 81.6 MUg/m3. The birth weight of newborns decreased
significantly with prenatal TVOC exposure (beta=-45.89, P=0.04). The adjusted
mean body weight was 300 g lower in the high-TVOC group (?75th) compared with
that in the low-exposure group (<75th).CONCLUSIONThese results indicate that
elevated exposure to TVOCs during the prenatal period may adversely influence
early postnatal growth.
PMID- 28422945
TI - Growth pattern and final height of very preterm vs. very low birth weight
infants.
AB - BackgroundBoth very preterm (VP; i.e., gestational age <32 weeks) and very low
birth weight (VLBW; i.e., birth weight <1,500 g) are used as inclusion criteria
by studies on preterm birth. We aimed to quantify the impact of these entities on
postnatal growth until final height.MethodsSubjects born VP and/or with VLBW from
the Project On Preterm and Small-for-gestational-age infants cohort were
classified as follows: (1) VP+/VLBW+ (n=495), (2) VP+/VLBW- (n=207), or (3) VP
/VLBW+ (n=296) infants. Anthropometric data were collected at birth, 3, 6, 12,
and 24 months' corrected age, and at 5 and 19 years. At 19 years, 590/998 (59%)
of the subjects enrolled in 1983 were followed up.ResultsBirth size was smallest
in the VP-/VLBW+ group compared with the VP+/VLBW+ and VP+/VLBW- groups. During
childhood, length, weight, and head circumference SD scores increased in the VP
/VLBW+ group, whereas SD scores in the VP+/VLBW+ and VP+/VLBW- groups either
remained stable or decreased. Despite catch-up growth, VP-/VLBW+ infants remained
the shortest and lightest at age 19.ConclusionClassification on the basis of VP
and VLBW impacts growth, causing different growth patterns for infants born
VP+/VLBW+, VP+/VLBW-, or VP-/VLBW+. For future studies, we recommend, at least
for industrialized countries, including preterm infants based on gestational age.
PMID- 28422946
TI - Pediatric Cushing disease: disparities in disease severity and outcomes in the
Hispanic and African-American populations.
AB - BackgroundLittle is known about the contribution of racial and socioeconomic
disparities to severity and outcomes in children with Cushing disease
(CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African
American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study.
A 10-point index for rating severity (CD severity) incorporated the degree of
hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements,
disease duration, and tumor characteristics. Race, ethnicity, age, gender, local
obesity prevalence, estimated median income, and access to care were assessed in
regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group
was worse than that in the non-HW group (4.9+/-2.0 vs. 4.1+/-1.9, P=0.023);
driving factors included higher cortisol levels and larger tumor size. Multiple
regression models confirmed that race (P=0.027) and older age (P=0.014) were the
most important predictors of worse CD severity. When followed up a median of 2.3
years after surgery, the relative risk for persistent CD combined with recurrence
was 2.8 times higher in the HI/AA group compared with that in the non-HW group
(95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving
forces for the discrepancy in severity of CD are older age and race/ethnicity.
Importantly, the risk for persistent and recurrent CD was higher in minority
children.
PMID- 28422947
TI - Factors affecting the cognitive profile of 11-year-old children born very
preterm.
AB - BackgroundPreterm birth is a risk for cognitive development. This study assessed
the cognitive profile of children born very preterm at the age of 11 years as
well as the associated risk factors.MethodsA total of 128 children born very
preterm were included. Magnetic resonance imaging was performed at term age.
Cognitive development was assessed using the full-scale intelligence quotient
(IQ) and four domains of the Wechsler Intelligence Scale for Children, fourth
edition (WISC-IV), Finnish translation. The results were compared with test
norms.ResultsMost study children performed at average (51%) or low average (21%)
levels in the full-scale IQ assessment. The correlation between 5- and 11-year
full-scale IQ was 0.73 (P<0.001). Compared with the normative data, children born
very preterm performed poorer in all domains of the cognitive profile. The only
significant risk factor for poor general cognition was major brain pathology.
When considering all four domains of WISC-IV, low paternal education, male
gender, and low birth weight z score were also found to be significant risk
factors.ConclusionsLess than one-third of the children born very preterm
performed below the low average cognitive level at 11 years of age. Specific
neonatal and sociodemographic risk factors were identified as affecting the
cognitive profile.
PMID- 28422948
TI - Beyond the uterine environment: a nonhuman primate model to investigate maternal
fetal and neonatal outcomes following chronic intrauterine infection.
AB - BackgroundIntrauterine infection is a significant cause of early preterm birth.
We have developed a fetal-neonatal model in the rhesus macaque to determine the
impact of chronic intrauterine infection with Ureaplasma parvum on early neonatal
reflexes and brain development.MethodsTime-mated, pregnant rhesus macaques were
randomized to be inoculated with U. parvum (serovar 1; 105 c.f.u.) or control
media at ~120 days' gestational age (dGA). Neonates were delivered by elective
hysterotomy at 135-147 dGA (term=167d), stabilized, and cared for in our nonhuman
primate neonatal intensive care unit. Neonatal reflex behaviors were assessed
from birth, and fetal and postnatal brain magnetic resonance imaging (MRI) was
performed.ResultsA total of 13 preterm and 5 term macaque infants were included
in the study. Ten preterm infants survived to 6 months of age. U. parvum-infected
preterm neonates required more intensive respiratory support than did control
infants. MRI studies suggested a potential perturbation of brain growth and white
matter maturation with exposure to intra-amniotic infection.ConclusionWe have
demonstrated the feasibility of longitudinal fetal-neonatal studies in the
preterm rhesus macaque after chronic intrauterine infection. Future studies will
examine long-term neurobehavioral outcomes, cognitive development,
neuropathology, and in vivo brain imaging to determine the safety of antenatal
antibiotic treatment for intrauterine infection.
PMID- 28422949
TI - Heparin-binding EGF-like growth factor promotes neuronal nitric oxide synthase
expression and protects the enteric nervous system after necrotizing
enterocolitis.
AB - BackgroundNeonatal necrotizing enterocolitis (NEC) is associated with alterations
of the enteric nervous system (ENS), with loss of neuronal nitric oxide synthase
(nNOS)-expressing neurons in the intestine. The aim of this study was to
investigate the roles of heparin-binding EGF-like growth factor (HB-EGF) in
neural stem cell (NSC) differentiation, nNOS expression, and effects on ENS
integrity during experimental NEC.MethodsThe effects of HB-EGF on NSC
differentiation and nNOS production were determined using cultured enteric NSCs.
Myenteric neuronal subpopulations were examined in HB-EGF knockout mice. Rat pups
were exposed to experimental NEC, and the effects of HB-EGF treatment on nNOS
production and intestinal neuronal apoptosis were determined.ResultsHB-EGF
promotes NSC differentiation, with increased nNOS production in differentiated
neurons and glial cells. Moreover, loss of nNOS-expressing neurons in the
myenteric plexus and impaired neurite outgrowth were associated with absence of
the HB-EGF gene. In addition, administration of HB-EGF preserves nNOS expression
in the myenteric plexus and reduces enteric neuronal apoptosis during
experimental NEC.ConclusionHB-EGF promotes the differentiation of enteric NSCs
into neurons in a nitric oxide (NO)-dependent manner, and protects the ENS from
NEC-induced injury, providing new insights into potential therapeutic strategies
for the treatment of NEC in the future.
PMID- 28422950
TI - Application of high-resolution array comparative genomic hybridization in
children with unknown syndromic microcephaly.
AB - BackroundMicrocephaly can either be isolated or it may coexist with other
neurological entities and/or multiple congenital anomalies, known as syndromic
microcephaly. Although many syndromic cases can be classified based on the
characteristic phenotype, some others remain uncertain and require further
investigation. The present study describes the application of array-comparative
genomic hybridization (array-CGH) as a diagnostic tool for the study of patients
with clinically unknown syndromic microcephaly.MethodsFrom a cohort of 210
unrelated patients referred with syndromic microcephaly, we applied array-CGH
analysis in 53 undiagnosed cases. In all the 53 cases except one, previous
standard karyotype was negative. High-resolution 4 * 180K and 1 * 244K Agilent
arrays were used in this study.ResultsIn 25 out of the 53 patients with
microcephaly among other phenotypic anomalies, array-CGH revealed copy number
variations (CNVs) ranging in size between 15 kb and 31.6 Mb. The identified CNVs
were definitely causal for microcephaly in 11/53, probably causal in 7/53, and
not causal for microcephaly in 7/53 patients. Genes potentially contributing to
brain deficit were revealed in 16/53 patients.ConclusionsArray-CGH contributes to
the elucidation of undefined syndromic microcephalic cases by permitting the
discovery of novel microdeletions and/or microduplications. It also allows a more
precise genotype-phenotype correlation by the accurate definition of the
breakpoints in the deleted/duplicated regions.
PMID- 28422951
TI - Helicobacter pylori infection and serum leptin, obestatin, and ghrelin levels in
Mexican schoolchildren.
AB - BackgroundThere is little information about the possible role of Helicobacter
pylori infection on appetite-regulating peptides in children. This study
evaluated the association between H. pylori infection and serum levels of
ghrelin, leptin, and obestatin in schoolchildren.MethodsOne hundred seventy-eight
schoolchildren, students at boarding schools in Mexico City, participated. H.
pylori infection status was determined every 6 months for 1 year by a breath test
using 13C-urea; schoolchildren with consistently positive or negative results
were selected to participate. Age, sex, and body mass index (BMI) were recorded.
Serum concentrations of total ghrelin, leptin, and obestatin via specific enzyme
linked immunosorbent assays were determined.ResultsSchoolchildren with H. pylori
infection had lower concentration of leptin, -0.54 pg/ml (95% CI: -0.98 to
0.09), compared to the schoolchildren without infection, after adjustment by age,
gender, and BMI. And the children with the infection had a median of obestatin
lower in 0.99 ng/ml (95% CI: -1.93 to -0.06) compared with the uninfected
children after adjustment by BMI.ConclusionAssociation was found between H.
pylori infection and decreased serum concentrations of leptin and obestatin.
These results suggest that in schoolchildren, H. pylori infection affects the
levels of hormones implicated in regulating appetite and energy homeostasis.
PMID- 28422952
TI - When cancer needs what's non-essential.
AB - The non-essential amino acids serine and glycine are critical for proliferative
metabolism. A study in Nature now finds that dietary serine and glycine
deprivation inhibits growth of some tumours. Whether this dietary intervention is
effective depends on both the oncogenic context and tumour tissue of origin.
PMID- 28422953
TI - Great spotted cuckoo nestlings have no antipredatory effect on magpie or carrion
crow host nests in southern Spain.
AB - Host defences against cuckoo parasitism and cuckoo trickeries to overcome them
are a classic example of antagonistic coevolution. Recently it has been reported
that this relationship may turn to be mutualistic in the case of the carrion crow
(Corvus corone) and its brood parasite, the great spotted cuckoo (Clamator
glandarius), given that experimentally and naturally parasitized nests were
depredated at a lower rate than non-parasitized nests. This result was
interpreted as a consequence of the antipredatory properties of a fetid cloacal
secretion produced by cuckoo nestlings, which presumably deters predators from
parasitized host nests. This potential defensive mechanism would therefore
explain the detected higher fledgling success of parasitized nests during
breeding seasons with high predation risk. Here, in a different study population,
we explored the expected benefits in terms of reduced nest predation in naturally
and experimentally parasitized nests of two different host species, carrion crows
and magpies (Pica pica). During the incubation phase non-parasitized nests were
depredated more frequently than parasitized nests. However, during the nestling
phase, parasitized nests were not depredated at a lower rate than non-parasitized
nests, neither in magpie nor in carrion crow nests, and experimental
translocation of great spotted cuckoo hatchlings did not reveal causal effects
between parasitism state and predation rate of host nests. Therefore, our results
do not fit expectations and, thus, do not support the fascinating possibility
that great spotted cuckoo nestlings could have an antipredatory effect for host
nestlings, at least in our study area. We also discuss different possibilities
that may conciliate these with previous results, but also several alternative
explanations, including the lack of generalizability of the previously documented
mutualistic association.
PMID- 28422954
TI - Identification of the contribution of contact and aerial biomechanical parameters
in acrobatic performance.
AB - INTRODUCTION: Teaching acrobatic skills with a minimal amount of repetition is a
major challenge for coaches. Biomechanical, statistical or computer simulation
tools can help them identify the most determinant factors of performance. Release
parameters, change in moment of inertia and segmental momentum transfers were
identified in the prediction of acrobatics success. The purpose of the present
study was to evaluate the relative contribution of these parameters in
performance throughout expertise or optimisation based improvements. The counter
movement forward in flight (CMFIF) was chosen for its intrinsic dichotomy between
the accessibility of its attempt and complexity of its mastery. METHODS: Three
repetitions of the CMFIF performed by eight novice and eight advanced female
gymnasts were recorded using a motion capture system. Optimal aerial techniques
that maximise rotation potential at regrasp were also computed. A 14-segment
multibody-model defined through the Rigid Body Dynamics Library was used to
compute recorded and optimal kinematics, and biomechanical parameters. A stepwise
multiple linear regression was used to determine the relative contribution of
these parameters in novice recorded, novice optimised, advanced recorded and
advanced optimised trials. Finally, fixed effects of expertise and optimisation
were tested through a mixed-effects analysis. RESULTS AND DISCUSSION: Variation
in release state only contributed to performances in novice recorded trials.
Moment of inertia contribution to performance increased from novice recorded, to
novice optimised, advanced recorded, and advanced optimised trials. Contribution
to performance of momentum transfer to the trunk during the flight prevailed in
all recorded trials. Although optimisation decreased transfer contribution,
momentum transfer to the arms appeared. CONCLUSION: Findings suggest that novices
should be coached on both contact and aerial technique. Inversely, mainly
improved aerial technique helped advanced gymnasts increase their performance.
For both, reduction of the moment of inertia should be focused on. The method
proposed in this article could be generalized to any aerial skill learning
investigation.
PMID- 28422955
TI - Low cholesterol level associated with severity and outcome of spontaneous
intracerebral hemorrhage: Results from Taiwan Stroke Registry.
AB - The relationship between cholesterol level and hemorrhagic stroke is
inconclusive. We hypothesized that low cholesterol levels may have association
with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes.
This study used data obtained from a multi-center stroke registry program in
Taiwan. We categorized acute spontaneous ICH patients, based on their baseline
levels of total cholesterol (TC) measured at admission, into 3 groups with <160,
160-200 and >200 mg/dL of TC. We evaluated risk of having initial stroke
severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and
unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality)
after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5+/-14.2
years; 64.2% men) were included in this study and 854 (34.9%) of them had
baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe
neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95%
confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11
1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL
and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR
3.94, 95% CI 1.76-8.80). Prior use of lipid-lowering drugs (2.8% of the ICH
population) was not associated with initial severity and 3-month outcomes. A
total cholesterol level lower than 160 mg/dL was common in patients with acute
ICH and was associated with greater neurological severity on presentation and
poor 3-month outcomes, especially with lower BMI.
PMID- 28422956
TI - Chronic activation of PPARalpha with fenofibrate reduces autophagic proteins in
the liver of mice independent of FGF21.
AB - Autophagy is a catabolic mechanism to degrade cellular components to maintain
cellular energy levels during starvation, a condition where PPARalpha may be
activated. Here we report a reduced autophagic capacity in the liver following
chronic activation of PPARalpha with fenofibrate (FB) in mice. Chronic
administration of the PPARalpha agonist FB substantially reduced the levels of
multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1)
which were associated with a decrease in the light chain LC3II/LC3I ratio and the
accumulation of p62. This was concomitant with an increase in the expression of
lipogenic proteins mSREBP1c, ACC, FAS and SCD1. These effects of FB were
completely abolished in PPARalpha-/- mice but remained intact in mice with global
deletion of FGF21, a key downstream mediator for PPARalpha-induced effects.
Further studies showed that decreased the content of autophagy proteins by FB was
associated with a significant reduction in the level of FoxO1, a transcriptional
regulator of autophagic proteins, which occurred independently of both mTOR and
Akt. These findings suggest that chronic stimulation of PPARalpha may suppress
the autophagy capacity in the liver as a result of reduced content of a number of
autophagy-associated proteins independent of FGF21.
PMID- 28422957
TI - Towards a theory of cortical columns: From spiking neurons to interacting neural
populations of finite size.
AB - Neural population equations such as neural mass or field models are widely used
to study brain activity on a large scale. However, the relation of these models
to the properties of single neurons is unclear. Here we derive an equation for
several interacting populations at the mesoscopic scale starting from a
microscopic model of randomly connected generalized integrate-and-fire neuron
models. Each population consists of 50-2000 neurons of the same type but
different populations account for different neuron types. The stochastic
population equations that we find reveal how spike-history effects in single
neuron dynamics such as refractoriness and adaptation interact with finite-size
fluctuations on the population level. Efficient integration of the stochastic
mesoscopic equations reproduces the statistical behavior of the population
activities obtained from microscopic simulations of a full spiking neural network
model. The theory describes nonlinear emergent dynamics such as finite-size
induced stochastic transitions in multistable networks and synchronization in
balanced networks of excitatory and inhibitory neurons. The mesoscopic equations
are employed to rapidly integrate a model of a cortical microcircuit consisting
of eight neuron types, which allows us to predict spontaneous population
activities as well as evoked responses to thalamic input. Our theory establishes
a general framework for modeling finite-size neural population dynamics based on
single cell and synapse parameters and offers an efficient approach to analyzing
cortical circuits and computations.
PMID- 28422958
TI - Modern alongside traditional taxonomy-Integrative systematics of the genera
Gymnangium Hincks, 1874 and Taxella Allman, 1874 (Hydrozoa, Aglaopheniidae).
AB - We studied the diversity within the former genus Gymnangium in the South West
Indian Ocean by using an integrative approach of both traditional (morphology
based) and modern molecular taxonomy. Nine species were recorded in the material
collected. A total of 97 16S mitochondrial DNA sequences and 54 Calmodulin
nuclear sequences from eight Gymnangium/Taxella species were analyzed. We found
both morphological and molecular differences in the studied Gymnangium species
that make it necessary to split the genus. It is proposed to revalidate the genus
Taxella which is currently regarded as a synonym of Gymnangium. Two species of
the genus Taxella (T. eximia and T. gracilicaulis), until now regarded as
distinct species based on morphological characteristics, cluster together in one
phylogenetic clade. Possible explanations are discussed. Two species from
Madagascar new to science are herein described and rare species from the Indian
Ocean islands are re-described.
PMID- 28422959
TI - Molecular regionalization of the developing amphioxus neural tube challenges
major partitions of the vertebrate brain.
AB - All vertebrate brains develop following a common Bauplan defined by
anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely
conserved differential expression of gene markers. However, it is still unclear
how this Bauplan originated during evolution. We studied the relative expression
of 48 genes with key roles in vertebrate neural patterning in a representative
amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central
nervous system (CNS) from a neural plate that is homologous to that of
vertebrates, allowing direct topological comparisons. The resulting
genoarchitectonic model revealed that the amphioxus incipient neural tube is
unexpectedly complex, consisting of several AP and DV molecular partitions.
Strikingly, comparison with vertebrates indicates that the vertebrate thalamus,
pretectum, and midbrain domains jointly correspond to a single amphioxus region,
which we termed Di-Mesencephalic primordium (DiMes). This suggests that these
domains have a common developmental and evolutionary origin, as supported by
functional experiments manipulating secondary organizers in zebrafish and mice.
PMID- 28422960
TI - Predicting the impact of Lynch syndrome-causing missense mutations from
structural calculations.
AB - Accurate methods to assess the pathogenicity of mutations are needed to fully
leverage the possibilities of genome sequencing in diagnosis. Current data-driven
and bioinformatics approaches are, however, limited by the large number of new
variations found in each newly sequenced genome, and often do not provide direct
mechanistic insight. Here we demonstrate, for the first time, that saturation
mutagenesis, biophysical modeling and co-variation analysis, performed in silico,
can predict the abundance, metabolic stability, and function of proteins inside
living cells. As a model system, we selected the human mismatch repair protein,
MSH2, where missense variants are known to cause the hereditary cancer
predisposition disease, known as Lynch syndrome. We show that the majority of
disease-causing MSH2 mutations give rise to folding defects and proteasome
dependent degradation rather than inherent loss of function, and accordingly our
in silico modeling data accurately identifies disease-causing mutations and
outperforms the traditionally used genetic disease predictors. Thus, in
conclusion, in silico biophysical modeling should be considered for making
genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps
other hereditary diseases.
PMID- 28422961
TI - Characterization of the mechanism of drug-drug interactions from PubMed using
MeSH terms.
AB - Identifying drug-drug interaction (DDI) is an important topic for the development
of safe pharmaceutical drugs and for the optimization of multidrug regimens for
complex diseases such as cancer and HIV. There have been about 150,000
publications on DDIs in PubMed, which is a great resource for DDI studies. In
this paper, we introduced an automatic computational method for the systematic
analysis of the mechanism of DDIs using MeSH (Medical Subject Headings) terms
from PubMed literature. MeSH term is a controlled vocabulary thesaurus developed
by the National Library of Medicine for indexing and annotating articles. Our
method can effectively identify DDI-relevant MeSH terms such as drugs, proteins
and phenomena with high accuracy. The connections among these MeSH terms were
investigated by using co-occurrence heatmaps and social network analysis. Our
approach can be used to visualize relationships of DDI terms, which has the
potential to help users better understand DDIs. As the volume of PubMed records
increases, our method for automatic analysis of DDIs from the PubMed database
will become more accurate.
PMID- 28422963
TI - A large-scale analysis of sex differences in facial expressions.
AB - There exists a stereotype that women are more expressive than men; however,
research has almost exclusively focused on a single facial behavior, smiling. A
large-scale study examines whether women are consistently more expressive than
men or whether the effects are dependent on the emotion expressed. Studies of
gender differences in expressivity have been somewhat restricted to data
collected in lab settings or which required labor-intensive manual coding. In the
present study, we analyze gender differences in facial behaviors as over 2,000
viewers watch a set of video advertisements in their home environments. The
facial responses were recorded using participants' own webcams. Using a new
automated facial coding technology we coded facial activity. We find that women
are not universally more expressive across all facial actions. Nor are they more
expressive in all positive valence actions and less expressive in all negative
valence actions. It appears that generally women express actions more frequently
than men, and in particular express more positive valence actions. However,
expressiveness is not greater in women for all negative valence actions and is
dependent on the discrete emotional state.
PMID- 28422962
TI - Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic
steatohepatitis in obese Ldlr-/- mice.
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major public health
concern in western societies. Nonalcoholic steatohepatitis (NASH), the
progressive form of NAFLD, is characterized by hepatic steatosis, inflammation,
oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and
hepatocellular carcinoma. NASH is predicted to be the leading cause of liver
transplants by 2020. Despite this growing public health concern, there remain no
Food and Drug Administration (FDA) approved NASH treatments. Using Ldlr -/- mice
as a preclinical model of western diet (WD)-induced NASH, we previously
established that dietary supplementation with docosahexaenoic acid (DHA,
22:6,omega3) attenuated WD-induced NASH in a prevention study. Herein, we
evaluated the capacity of DHA supplementation of the WD and a low fat diet to
fully reverse NASH in mice with pre-existing disease. METHODS: Ldlr -/- mice fed
the WD for 22 wks developed metabolic syndrome (MetS) and a severe NASH
phenotype, including obesity, dyslipidemia, hyperglycemia, hepatic steatosis,
inflammation, fibrosis and low hepatic polyunsaturated fatty acid (PUFA) content.
These mice were randomized to 5 groups: a baseline group (WDB, sacrificed at 22
wks) and 4 treatments: 1) WD + olive oil (WDO); 2) WD + DHA (WDD); 3) returned to
chow + olive oil (WDChO); or 4) returned to chow + DHA (WDChD). The four
treatment groups were maintained on their respective diets for 8 wks. An
additional group was maintained on standard laboratory chow (Reference Diet, RD)
for the 30-wk duration of the study. RESULTS: When compared to the WDB group, the
WDO group displayed increased hepatic expression of genes linked to inflammation
(Opn, Il1rn, Gdf15), hepatic fibrosis (collagen staining, Col1A1, Thbs2, Lox)
reflecting disease progression. Mice in the WDD group, in contrast, had increased
hepatic C20-22 omega3 PUFA and no evidence of NASH progression. MetS and NASH
markers in the WDChO or WDChD groups were significantly attenuated and marginally
different from the RD group, reflecting disease remission. CONCLUSION: While
these studies establish that DHA supplementation of the WD blocks WD-induced NASH
progression, DHA alone does not promote full remission of diet-induced MetS or
NASH.
PMID- 28422964
TI - Effect of women's age on embryo morphology, cleavage rate and competence-A
multicenter cohort study.
AB - This multicenter cohort study on embryo assessment and outcome data from 11,744
IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of
women's age on oocyte, zygote, embryo morphology and cleavage parameters, as well
as cycle outcome measures corrected for confounding factors as center, partner's
age and referral diagnosis. Cycle outcome data confirmed the well-known effect of
women's age. Oocyte nuclear maturation and proportion of 2 pro-nuclear (2PN)
zygotes were not affected by age, while a significant increase in 3PN zygotes was
observed in both IVF and ICSI (p<0.0001) with increasing age. Maternal age had no
effect on cleavage parameters or on the morphology of the embryo day 2 post
insemination. Interestingly, initial hCG value after single embryo transfer
followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and
ICSI (p = 0.001) cycles. For the first time, we show that a woman's age does
impose a significant footprint on early embryo morphological development (3PN).
In addition, the developmentally competent embryos were associated with increased
initial hCG values as the age of the women increased. Further studies are needed
to elucidate, if this increase in initial hCG value with advancing maternal age
is connected to the embryo or the uterus.
PMID- 28422965
TI - Diet and condition of mesopredators on coral reefs in relation to shark
abundance.
AB - Reef sharks may influence the foraging behaviour of mesopredatory teleosts on
coral reefs via both risk effects and competitive exclusion. We used a "natural
experiment" to test the hypothesis that the loss of sharks on coral reefs can
influence the diet and body condition of mesopredatory fishes by comparing two
remote, atoll-like reef systems, the Rowley Shoals and the Scott Reefs, in
northwestern Australia. The Rowley Shoals are a marine reserve where sharks are
abundant, whereas at the Scott Reefs numbers of sharks have been reduced by
centuries of targeted fishing. On reefs where sharks were rare, the gut contents
of five species of mesopredatory teleosts largely contained fish while on reefs
with abundant sharks, the same mesopredatory species consumed a larger proportion
of benthic invertebrates. These measures of diet were correlated with changes in
body condition, such that the condition of mesopredatory teleosts was
significantly poorer on reefs with higher shark abundance. Condition was defined
as body weight, height and width for a given length and also estimated via
several indices of condition. Due to the nature of natural experiments,
alternative explanations cannot be discounted. However, the results were
consistent with the hypothesis that loss of sharks may influence the diet and
condition of mesopredators and by association, their fecundity and trophic role.
Regardless of the mechanism (risk effects, competitive release, or other), our
findings suggest that overfishing of sharks has the potential to trigger trophic
cascades on coral reefs and that further declines in shark populations globally
should be prevented to protect ecosystem health.
PMID- 28422966
TI - Taming the late Quaternary phylogeography of the Eurasiatic wild ass through
ancient and modern DNA.
AB - Taxonomic over-splitting of extinct or endangered taxa, due to an incomplete
knowledge of both skeletal morphological variability and the geographical ranges
of past populations, continues to confuse the link between isolated extant
populations and their ancestors. This is particularly problematic with the genus
Equus. To more reliably determine the evolution and phylogeographic history of
the endangered Asiatic wild ass, we studied the genetic diversity and inter
relationships of both extinct and extant populations over the last 100,000 years,
including samples throughout its previous range from Western Europe to Southwest
and East Asia. Using 229 bp of the mitochondrial hypervariable region, an
approach which allowed the inclusion of information from extremely poorly
preserved ancient samples, we classify all non-African wild asses into eleven
clades that show a clear phylogeographic structure revealing their phylogenetic
history. This study places the extinct European wild ass, E. hydruntinus, the
phylogeny of which has been debated since the end of the 19th century, into its
phylogenetic context within the Asiatic wild asses and reveals recent
mitochondrial introgression between populations currently regarded as separate
species. The phylogeographic organization of clades resulting from these efforts
can be used not only to improve future taxonomic determination of a poorly
characterized group of equids, but also to identify historic ranges,
interbreeding events between various populations, and the impact of ancient
climatic changes. In addition, appropriately placing extant relict populations
into a broader phylogeographic and genetic context can better inform ongoing
conservation strategies for this highly-endangered species.
PMID- 28422967
TI - Craniodental and humeral morphology of a new species of Masrasector
(Teratodontinae, Hyaenodonta, Placentalia) from the late Eocene of Egypt and
locomotor diversity in hyaenodonts.
AB - Hyaenodonta is a diverse clade of carnivorous mammals that were part of
terrestrial faunas in the Paleogene of Eurasia and North America, but the oldest
record for the group is Afro-Arabian, making the record there vital for
understanding the evolution of this wide-spread group. Previous studies show an
ancient split between two major clades of hyaenodonts that converged in
hypercarnivory: Hyainailourinae and Hyaenodontinae. These clades are each
supported by cranial characters. Phylogenetic analyses of hyaenodonts also
support the monophyly of Teratodontinae, an Afro-Arabian clade of mesocarnivorous
to hypercarnivorous hyaenodonts. Unfortunately, the cranial anatomy of
teratodontines is poorly known, and aligning the clade with other lineages has
been difficult. Here, a new species of the phylogenetically controversial
teratodontine Masrasector is described from Locality 41 (latest Priabonian, late
Eocene) from the Fayum Depression, Egypt. The hypodigm includes the most complete
remains of a Paleogene teratodontine, including largely complete crania, multiple
dentaries, and isolated humeri. Standard and "tip-dating" Bayesian analyses of a
character-taxon matrix that samples cranial, postcranial, and dental characters
support a monophyletic Masrasector within Teratodontinae, which is consistently
placed as a close sister group of Hyainailouridae. The cranial morphology of
Masrasector provides new support for an expanded Hyainailouroidea (Teratodontinae
+ Hyainailouridae), particularly characters of the nuchal crest, palate, and
basicranium. A discriminant function analysis was performed using measurements of
the distal humerus from a diverse sample of extant carnivorans to infer the
locomotor habits of Masrasector. Masrasector was assigned to the "terrestrial"
locomotor category, a result consistent with the well-defined medial trochlear
ridges, and moderately developed supinator crests of the specimens. Masrasector
appears to have been a fast-moving terrestrial form with a diverse diet. These
specimens considerably improve our understanding of Teratodontinae, an ancient
member of the Afro-Arabian mammalian fauna, and our understanding of hyaenodont
diversity before the dispersal of Carnivora to the continent near the end of the
Paleogene.
PMID- 28422968
TI - The impact of a point-of-care testing device on CVD risk assessment completion in
New Zealand primary-care practice: A cluster randomised controlled trial and
qualitative investigation.
AB - OBJECTIVES: To assess the effect of a point of care (POC) device for testing
lipids and HbA1c in addition to testing by community laboratory facilities (usual
practice) on the completion of cardiovascular disease (CVD) risk assessments in
general practice. METHODS: We conducted a pragmatic, cluster randomised
controlled trial in 20 New Zealand general practices stratified by size and
rurality and randomised to POC device plus usual practice or usual practice alone
(controls). Patients aged 35-79 years were eligible if they met national
guideline criteria for CVD risk assessment. Data on CVD risk assessments were
aggregated using a web-based decision support programme common to each practice.
Data entered into the on-line CVD risk assessment form could be saved pending
blood test results. The primary outcome was the proportion of completed CVD risk
assessments. Qualitative data on practice processes for CVD risk assessment and
feasibility of POC testing were collected at the end of the study by interviews
and questionnaire. The POC testing was supported by a comprehensive quality
assurance programme. RESULTS: A CVD risk assessment entry was recorded for 7421
patients in 10 POC practices and 6217 patients in 10 control practices; 99.5% of
CVD risk assessments had complete data in both groups (adjusted odds ratio 1.02
[95%CI 0.61-1.69]). There were major external influences that affected the trial:
including a national performance target for CVD risk assessment and changes to
CVD guidelines. All practices had invested in systems and dedicated staff time to
identify and follow up patients to completion. However, the POC device was viewed
by most as an additional tool rather than as an opportunity to review practice
work flow and leverage the immediate test results for patient education and CVD
risk management discussions. Shortly after commencement, the trial was halted due
to a change in the HbA1c test assay performance. The trial restarted after the
manufacturing issue was rectified but this affected the end use of the device.
CONCLUSIONS: Performance incentives and external influences were more powerful
modifiers of practice behaviours than the POC device in relation to CVD risk
assessment completion. The promise of combining risk assessment, communication
and management within one consultation was not realised. With shifts in policy
focus, the utility of POC devices for patient engagement in CVD preventive care
may be demonstrated if fully integrated into the clinical setting. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN12613000607774.
PMID- 28422969
TI - A new species of Tometes Valenciennes 1850 (Characiformes: Serrasalmidae) from
Tocantins-Araguaia River Basin based on integrative analysis of molecular and
morphological data.
AB - A new large serrasalmid species of Tometes is described from the Tocantins
Araguaia River Basin. Tometes siderocarajensis sp. nov. is currently found in the
rapids of the Itacaiunas River Basin, and formerly inhabited the lower Tocantins
River. The new species can be distinguished from all congeners, except from T.
ancylorhynchus, by the presence of lateral space between 1st and 2nd premaxillary
teeth, and by the absence of lateral cusps in these two teeth. However, T.
siderocarajensis sp. nov. can be differentiated from syntopic congener T.
ancylorhynchus by an entirely black with mottled red body in live specimens,
densely pigmented pelvic fins with a high concentration of dark chromatophores,
and the presence of 39 to 41 rows of circumpeduncular scales (vs. silvery body
coloration with slightly reddish overtones on middle flank during breeding period
in live specimens, hyaline to slightly pale coloration on distalmost region of
pelvic fins, and 30 to 36 rows of circumpeduncular scales). Additionally,
molecular sequence shows that T. siderocarajensis sp. nov. is reciprocally
monophyletic, and diagnosable from all congeners by having two autapomorphic
molecular characters in the mitochondrial gene COI. The phylogenetic
reconstruction still show that T. siderocarajensis sp. nov. is closely related to
T. trilobatus. This is the first molecular study using an integrative taxonomic
approach based on morphological and molecular sequence data for all described
species of Tometes. These findings increase the number of formally described
species of Tometes to seven. A key to the Tometes species is provided.
PMID- 28422970
TI - The gut microbiota as a modulator of innate immunity during melioidosis.
AB - BACKGROUND: Melioidosis, caused by the Gram-negative bacterium Burkholderia
pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics.
The gut microbiota supports local mucosal immunity and is increasingly recognized
as a protective mediator in host defenses against systemic infection. Here, we
aimed to characterize the composition and function of the intestinal microbiota
during experimental melioidosis. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice
were infected intranasally with B. pseudomallei and sacrificed at different time
points to assess bacterial loads and inflammation. In selected experiments, the
gut microbiota was disrupted with broad-spectrum antibiotics prior to
inoculation. Fecal bacterial composition was analyzed by means of IS-pro, a 16S
23S interspacer region-based profiling method. A marked shift in fecal bacterial
composition was seen in all mice during systemic B. pseudomallei infection with a
strong increase in Proteobacteria and decrease in Actinobacteria, with an
increase in bacterial diversity. We found enhanced early dissemination of B.
pseudomallei and systemic inflammation during experimental melioidosis in
microbiota-disrupted mice compared with controls. Whole-genome transcriptional
profiling of the lung identified several genes that were differentially expressed
between mice with a normal or disrupted intestinal microbiota. Genes involved in
acute phase signaling, including macrophage-related signaling pathways were
significantly elevated in microbiota disrupted mice. Compared with controls,
alveolar macrophages derived from antibiotic pretreated mice showed a diminished
capacity to phagocytose B. pseudomallei. This might in part explain the observed
protective effect of the gut microbiota in the host defense against pneumonia
derived melioidosis. CONCLUSIONS/SIGNIFICANCE: Taken together, these data
identify the gut microbiota as a potential modulator of innate immunity during B.
pseudomallei infection.
PMID- 28422971
TI - Comparison of chemical-use between hydraulic fracturing, acidizing, and routine
oil and gas development.
AB - The potential hazards and risks associated with well-stimulation in
unconventional oil and gas development (hydraulic fracturing, acid fracturing,
and matrix acidizing) have been investigated and evaluated and federal and state
regulations requiring chemical disclosure for well-stimulation have been
implemented as part of an overall risk management strategy for unconventional oil
and gas development. Similar evaluations for chemicals used in other routine oil
and gas development activities, such as maintenance acidizing, gravel packing,
and well drilling, have not been previously conducted, in part due to a lack of
reliable information concerning on-field chemical-use. In this study, we compare
chemical-use between routine activities and the more closely regulated well
stimulation activities using data collected by the South Coast Air Quality
Monitoring District (SCAQMD), which mandates the reporting of both unconventional
and routine on-field chemical-use for parts of Southern California. Analysis of
this data shows that there is significant overlap in chemical-use between so
called unconventional activities and routine activities conducted for well
maintenance, well-completion, or rework. A comparison within the SCAQMD shows a
significant overlap between both types and amounts of chemicals used for well
stimulation treatments included under State mandatory-disclosure regulations and
routine treatments that are not included under State regulations. A comparison
between SCAQMD chemical-use for routine treatments and state-wide chemical-use
for hydraulic fracturing also showed close similarity in chemical-use between
activities covered under chemical disclosure requirements (e.g. hydraulic
fracturing) and many other oil and gas field activities. The results of this
study indicate regulations and risk assessments focused exclusively on chemicals
used in well-stimulation activities may underestimate potential hazard or risk
from overall oil field chemical-use.
PMID- 28422973
TI - Camera trap arrays improve detection probability of wildlife: Investigating study
design considerations using an empirical dataset.
AB - Camera trapping is a standard tool in ecological research and wildlife
conservation. Study designs, particularly for small-bodied or cryptic wildlife
species often attempt to boost low detection probabilities by using non-random
camera placement or baited cameras, which may bias data, or incorrectly estimate
detection and occupancy. We investigated the ability of non-baited, multi-camera
arrays to increase detection probabilities of wildlife. Study design components
were evaluated for their influence on wildlife detectability by iteratively
parsing an empirical dataset (1) by different sizes of camera arrays deployed (1
10 cameras), and (2) by total season length (1-365 days). Four species from our
dataset that represented a range of body sizes and differing degrees of presumed
detectability based on life history traits were investigated: white-tailed deer
(Odocoileus virginianus), bobcat (Lynx rufus), raccoon (Procyon lotor), and
Virginia opossum (Didelphis virginiana). For all species, increasing from a
single camera to a multi-camera array significantly improved detection
probability across the range of season lengths and number of study sites
evaluated. The use of a two camera array increased survey detection an average of
80% (range 40-128%) from the detection probability of a single camera across the
four species. Species that were detected infrequently benefited most from a
multiple-camera array, where the addition of up to eight cameras produced
significant increases in detectability. However, for species detected at high
frequencies, single cameras produced a season-long (i.e, the length of time over
which cameras are deployed and actively monitored) detectability greater than
0.75. These results highlight the need for researchers to be critical about
camera trap study designs based on their intended target species, as
detectability for each focal species responded differently to array size and
season length. We suggest that researchers a priori identify target species for
which inference will be made, and then design camera trapping studies around the
most difficult to detect of those species.
PMID- 28422972
TI - Challenges in enumeration of CTCs in breast cancer using techniques independent
of cytokeratin expression.
AB - INTRODUCTION: Given the current postulated plasticity between epithelial and
mesenchymal states of migratory cancer cells the detection of non-epithelial CTCs
is an important scientific and clinical goal. METHODS: We used the filtration
based ISET technology to enrich circulating tumour cells (CTCs) in early breast
cancer blood samples and identify them using a morphology-based
immunocytochemistry (ICC) approach. RESULTS: We found greater numbers of putative
CTCs by this approach than by the cytokeratin-based CellSearch technology, but a
high number of CTC false positives were identified in healthy volunteer samples
which were not reduced in successive blood draws. Preliminary work using an
oestrogen receptor (ER)-based multiplex ICC method in metastatic breast cancer
ISET samples indicated a low number of ER+ CTCs even at this advanced stage.
CONCLUSIONS: This work highlights the challenges in enumerating CTCs without
conventional epithelial markers.
PMID- 28422974
TI - Variation in benthic long-term data of transitional waters: Is interpretation
more than speculation?
AB - Biological long-term data series in marine habitats are often used to identify
anthropogenic impacts on the environment or climate induced regime shifts.
However, particularly in transitional waters, environmental properties like water
mass dynamics, salinity variability and the occurrence of oxygen minima not
necessarily caused by either human activities or climate change can attenuate or
mask apparent signals. At first glance it very often seems impossible to
interpret the strong fluctuations of e.g. abundances or species richness, since
abiotic variables like salinity and oxygen content vary simultaneously as well as
in apparently erratic ways. The long-term development of major macrozoobenthic
parameters (abundance, biomass, species numbers) and derivative macrozoobenthic
indices (Shannon diversity, Margalef, Pilou's evenness and Hurlbert) has been
successfully interpreted and related to the long-term fluctuations of salinity
and oxygen, incorporation of the North Atlantic Oscillation index (NAO index),
relying on the statistical analysis of modelled and measured data during 35 years
of observation at three stations in the south-western Baltic Sea. Our results
suggest that even at a restricted spatial scale the benthic system does not
appear to be tightly controlled by any single environmental driver and highlight
the complexity of spatially varying temporal response.
PMID- 28422975
TI - Children's weight changes according to maternal perception of the child's weight
and health: A prospective cohort of Peruvian children.
AB - The aim of the study was to estimate the association between maternal perception
of their child's health status and (mis)classification of their child's actual
weight with future weight change. We present cross-sectional and longitudinal
analyses from the Peruvian younger cohort of the Young Lives Study. For cross
sectional analysis, the exposure was maternal perception of child health status
(better, same or worse); the outcome was underestimation or overestimation of the
child's actual weight. Mothers were asked about their perception of their child's
weight (same, lighter or heavier than other children). Actual weight status was
defined with IOTF BMI cut-off points. For longitudinal analysis, the exposure was
(mis)classification of the child's actual weight; the outcome was the
standardized mean difference between follow-up and baseline BMI. A Generalized
Linear Model with Poisson family and log-link was used to report the prevalence
ratio (PR) and 95% confidence intervals (95% CI) for cross-sectional analyses. A
Linear Regression Model was used to report the longitudinal analysis as
coefficient estimates (beta) and 95% CI. Normal weight children who were
perceived as more healthy than other children were more likely to have their
weight overestimated (PR = 2.06); conversely, those who were perceived as less
healthy than other children were more likely to have their weight underestimated
(PR = 2.17). Mean follow-up time was 2.6 (SD: 0.3) years. Overall, underweight
children whose weight was overestimated were more likely to gain BMI (beta =
0.44); whilst overweight children whose weight was considered to be the same of
their peers (beta = -0.55), and those considered to be lighter than other
children (beta = -0.87), lost BMI. Maternal perception of the child's health
status seems to influence both overestimation and underestimation of the child's
actual weight status. Such weight (mis)perception may influence future BMI.
PMID- 28422976
TI - Reactivation or transformation? Motor memory consolidation associated with
cerebral activation time-locked to sleep spindles.
AB - Motor memory consolidation is thought to depend on sleep-dependent reactivation
of brain areas recruited during learning. However, up to this point, there has
been no direct evidence to support this assertion in humans, and the
physiological processes supporting such reactivation are unknown. Here,
simultaneous electroencephalographic and functional magnetic resonance imaging
(EEG-fMRI) recordings were conducted during post-learning sleep to directly
investigate the spindle-related reactivation of a memory trace formed during
motor sequence learning (MSL), and its relationship to overnight enhancement in
performance (reflecting consolidation). We show that brain regions within the
striato-cerebello-cortical network recruited during training on the MSL task, and
in particular the striatum, were also activated during sleep, time-locked to
spindles. Interestingly, the consolidated trace in the striatum was not simply
strengthened, but was transformed/reorganized from rostrodorsal (associative) to
caudoventral (sensorimotor) subregions. Moreover, the degree of the reactivation
was correlated with overnight improvements in performance. Altogether, the
present findings demonstrate that striatal reactivation linked to sleep spindles
in the post-learning night, is related to motor memory consolidation.
PMID- 28422977
TI - Defining the complex phenotype of severe systemic loxoscelism using a large
electronic health record cohort.
AB - OBJECTIVE: Systemic loxoscelism is a rare illness resulting from the bite of the
recluse spider and, in its most severe form, can lead to widespread hemolysis,
coagulopathy, and death. We aim to describe the clinical features and outcomes of
the largest known cohort of individuals with moderate to severe loxoscelism.
METHODS: We performed a retrospective, cross sectional study from January 1,
1995, to December 31, 2015, at a tertiary-care academic medical center, to
determine individuals with clinical records consistent with moderate to severe
loxoscelism. Age-, sex-, and race-matched controls were compared. Demographics,
clinical characteristics, laboratory measures, and outcomes of individuals with
loxoscelism are described. Case and control groups were compared with descriptive
statistics and phenome-wide association study (PheWAS). RESULTS: During the time
period, 57 individuals were identified as having moderate to severe loxoscelism.
Of these, only 33% had an antecedent spider bite documented. Median age of
individuals diagnosed with moderate to severe loxoscelism was 14 years old (IQR
9.0-24.0 years). PheWAS confirmed associations of systemic loxoscelism with 29
other phenotypes, e.g., rash, hemolytic anemia, and sepsis. Hemoglobin level
dropped an average of 3.1 g/dL over an average of 2.0 days (IQR 2.0-6.0). Lactate
dehydrogenase and total bilirubin levels were on average over two times their
upper limit of normal values. Eighteen individuals of 32 tested had a positive
direct antiglobulin (Coombs') test. Mortality was 3.5% (2/57 individuals).
CONCLUSION: Systemic loxoscelism is a rare but devastating process with only a
minority of patients recalling the toxic exposure; hemolysis reaches a peak at 2
days after admission, with some cases taking more than a week before recovery. In
endemic areas, suspicion for systemic loxoscelism should be high in individuals,
especially children and younger adults, presenting with a cutaneous ulcer and
hemolysis or coagulopathy, even in the absence of a bite exposure history.
PMID- 28422978
TI - The ESCRT regulator Did2 maintains the balance between long-distance endosomal
transport and endocytic trafficking.
AB - In highly polarised cells, like fungal hyphae, early endosomes function in both
endocytosis as well as long-distance transport of various cargo including mRNA
and protein complexes. However, knowledge on the crosstalk between these
seemingly different trafficking processes is scarce. Here, we demonstrate that
the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of
Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less
processive long-distance transport and abnormal shuttling of early endosomes.
Importantly, the late endosomal protein Rab7 and vacuolar protease Prc1 exhibit
increased shuttling on these aberrant endosomes suggesting defects in endosomal
maturation and identity. Consistently, molecular motors fail to attach
efficiently explaining the disturbed processive movement. Furthermore, the
endosomal mRNP linker protein Upa1 is hardly present on endosomes resulting in
defects in long-distance mRNA transport. In conclusion, the ESCRT regulator Did2
coordinates precise maturation of endosomes and thus provides the correct
membrane identity for efficient endosomal long-distance transport.
PMID- 28422979
TI - Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in
lung adenocarcinoma.
AB - BACKGROUND: 18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography
(PET) is a functional imaging modality based on glucose metabolism. The
correlation between EGFR or KRAS mutation status and the standardized uptake
value (SUV) of 18F-FDG PET scanning has not been fully elucidated. METHODS:
Correlations between EGFR or KRAS mutation status and clinicopathological factors
including SUVmax were statistically analyzed in 734 surgically resected lung
adenocarcinoma patients. Molecular causal relationships between EGFR or KRAS
mutation status and glucose metabolism were then elucidated in 62 lung
adenocarcinomas using cap analysis of gene expression (CAGE), a method to
determine and quantify the transcription initiation activities of mRNA across the
genome. RESULTS: EGFR and KRAS mutations were detected in 334 (46%) and 83 (11%)
of the 734 lung adenocarcinomas, respectively. The remaining 317 (43%) patients
had wild-type tumors for both genes. EGFR mutations were more frequent in tumors
with lower SUVmax. In contrast, no relationship was noted between KRAS mutation
status and SUVmax. CAGE revealed that 4 genes associated with glucose metabolism
(GPI, G6PD, PKM2, and GAPDH) and 5 associated with the cell cycle (ANLN, PTTG1,
CIT, KPNA2, and CDC25A) were positively correlated with SUVmax, although
expression levels were lower in EGFR-mutated than in wild-type tumors. No similar
relationships were noted with KRAS mutations. CONCLUSIONS: EGFR-mutated
adenocarcinomas are biologically indolent with potentially lower levels of
glucose metabolism than wild-type tumors. Several genes associated with glucose
metabolism and the cell cycle were specifically down-regulated in EGFR-mutated
adenocarcinomas.
PMID- 28422980
TI - Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to
Plasmodium falciparum.
AB - Multiple mechanisms such as genetic and epigenetic variations within a key gene
may play a role in malarial susceptibility and response to anti-malarial drugs in
the population. ABCB1 is one of the well-studied membrane transporter genes that
code for the P-glycoprotein (an efflux protein) and whose effect on malaria
disease predisposition and susceptibility to drugs remains to be understood. We
studied the association of single nucleotide variations in human ABCB1 that
influences its function in subjects with uncomplicated and complicated malaria
caused by Plasmodium falciparum (Pf). Global DNA methylation and ABCB1 DNA
promoter methylation levels were performed along with transcriptional response
and protein expression in subjects with malaria and healthy controls. The
rs2032582 locus was significantly associated with complicated and combined
malaria groups when compared to controls (p < 0.05). Significant DNA methylation
difference was noticed between case and control (p < 0.05). In addition, global
DNA methylation levels of the host DNA were inversely proportional to parasitemia
in individuals with Pf infection. Our study also revealed the correlation between
ABCB1 DNA promoter methylation with rs1128503 and rs2032582 polymorphisms in
malaria and was related to increased expression of ABCB1 protein levels in
complicated malaria group (p < 0.05) when compared to uncomplicated malaria and
control groups. The study provides evidence for multiple mechanisms that may
regulate the role of host ABCB1 function to mediate aetiology of malaria
susceptibility, prognosis and drug response. These may have clinical implications
and therapeutic application for various malarial conditions.
PMID- 28422981
TI - QTL analysis and dissection of panicle components in rice using advanced
backcross populations derived from Oryza Sativa cultivars HR1128 and
'Nipponbare'.
AB - Panicle traits are among the most important agronomic characters which directly
relate to yield in rice. Grain number (GN), panicle length (PL), primary branch
number (PBN), and secondary branch number (SBN) are the major components of rice
panicle structure, and are all controlled by quantitative trait loci (QTLs). In
our research, four advanced backcross overlapping populations (BIL152, BIL196a,
BIL196b, and BIL196b-156) carrying introgressed segments from chromosome 6 were
derived from an indica/japonica cross that used the super-hybrid rice restorer
line HR1128 and the international sequenced japonica cultivar 'Nipponbare' as the
donor and recurrent parents, respectively. The four panicle traits, GN, PL, PBN,
and SBN, were evaluated for QTL effects using the inclusive composite interval
mapping (ICIM) method in populations over two years at two sites. Results showed
that a total of twelve QTLs for GN, PL, PBN, and SBN were detected on chromosome
6. Based on marker loci physical positions, the QTLs were found to be tightly
linked to three important chromosomal intervals described as RM7213 to RM19962,
RM20000 to RM20210, and RM412 to RM20595. Three QTLs identified in this study,
PL6-5, PBN6-1, and PBN6-2, were found to be novel compared with previous studies.
A major QTL (PL6-5) for panicle length was detected in all four populations at
two locations, and its position was narrowed down to a 1.3Mb region on chromosome
6. Near isogenic lines (NILs) carrying PL6-5 will be developed for fine mapping
of the QTL, and our results will provide referable information for gene
excavation of panicle components in rice.
PMID- 28422982
TI - Assessment ecological risk of heavy metal caused by high-intensity land
reclamation in Bohai Bay, China.
AB - The article examines the detailed spatial and temporal distributions of coastal
reclamation in the northwest coast of Bohai Bay experiencing rapid coastal
reclamation in China from 1974 to 2010 in annual intervals. Moreover, soil
elements properties and spatial distribution in reclaimed area and inform the
future coastal ecosystems management was also analyzed. The results shows that
910.7 km2 of coastal wetlands have been reclaimed and conversed to industrial
land during the past 36 years. It covers intertidal beach, shallow sea and island
with a percentage of 76.0%, 23.5% and 0.5%, respectively. The average
concentration of Mn is 686.91mg/kg and the order of concentration of heavy metal
are Cr>Zn>As>Ni>Cu>Pb>Cd>Hg. We used the "space for time substitution" method to
test the soil properties changes after reclamation. The potential ecological risk
of heavy metal is in low level and the risk of Cd and As is relatively higher.
The ecosystem-based coastal protection and management are urgent to support
sustainable coastal ecosystems in Bohai bay in the future.
PMID- 28422983
TI - KIAA1199 promotes migration and invasion by Wnt/beta-catenin pathway and MMPs
mediated EMT progression and serves as a poor prognosis marker in gastric cancer.
AB - BACKGROUND: KIAA1199 was upregulated in diverse cancers, but the association of
KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells
and the related molecular mechanisms remain to be elucidated. METHODS: KIAA1199
expression was analysed by reverse transcription-polymerase chain reaction assay
(RT-PCR) and immunohistochemistry (IHC) in GC patient tissue. The small hairpin
RNA (shRNA) was applied for the knockdown of endogenous KIAA1199 in NCI-N87 and
AGS cells. MTT, colony formation, scratch wounding migration, transwell chamber
migration and invasion assays were employed respectively to investigate the role
of KIAA1199 in GC cells. The potential signaling pathway of KIAA1199 induced
migration and invasion was detected. RESULTS: KIAA1199 was upregulated in GC
tissue and was an essential independent marker for poor prognosis. Knockdown
KIAA1199 suppressed the proliferation, migration and invasion in GC cells.
KIAA1199 stimulated the Wnt/beta-catenin signaling pathway and the enzymatic
activity of matrix metalloproteinase (MMP) family members and thus accelerated
the epithelial-to-mesenchymal transition (EMT) progression in GC cells.
CONCLUSION: These findings demonstrated that KIAA1199 was upregulated in GC
tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as
an oncogene by promoting migration and invasion through the enhancement of
Wnt/beta-catenin signaling pathway and MMPs mediated EMT progression in GC cells.
PMID- 28422984
TI - The impact of atosiban on pregnancy outcomes in women undergoing in vitro
fertilization-embryo transfer: A meta-analysis.
AB - BACKGROUND: Atosiban is administered to women undergoing in vitro fertilization
embryo transfer (IVF-ET) to improve pregnancy outcomes. However, the results of
this treatment were controversial. We conducted this meta-analysis to investigate
whether atosiban improves pregnancy outcomes in the women undergoing in vitro
fertilization (IVF). METHODS: Databases of PubMed, EMBASE, Web of Science, China
BioMedicine, and Google Scholar were systematically searched. Meta-analyses were
performed to investigate whether atosiban improves pregnancy outcomes in the
women undergoing IVF. RESULTS: Our results showed that atosiban was associated
with higher implantation (OR = 1.63, 95% CI: 1.17-2.27; P = 0.004) and clinical
pregnancy (OR = 1.84, 95% CI: 1.31-2.57; P < 0.001) rates. However, atosiban
showed no significant association with the miscarriage, live birth, multiple
pregnancy or ectopic pregnancy rates. When a further subgroup analysis was
performed in the women undergoing repeated implantation failure (RIF),
implantation (OR = 1.93, 95% CI: 1.45-2.57; P < 0.001), clinical pregnancy (OR =
2.48, 95% CI: 1.70-3.64; P <0.001) and the live birth (OR = 2.89, 95% CI: 1.78
4.67; P < 0.001) rates were significantly higher in the case group. Nevertheless,
no significant difference was detected in the miscarriage and multiple pregnancy
rates between the case and control groups. CONCLUSION: Atosiban may be more
appropriate for women undergoing RIF and play only a limited role in improving
pregnancy outcomes in the general population of women undergoing IVF. These
conclusions should be verified in large and well-designed studies.
PMID- 28422985
TI - Revising mtDNA haplotypes of the ancient Hungarian conquerors with next
generation sequencing.
AB - As part of the effort to create a high resolution representative sequence
database of the medieval Hungarian conquerors we have resequenced the entire
mtDNA genome of 24 published ancient samples with Next Generation Sequencing,
whose haplotypes had been previously determined with traditional PCR based
methods. We show that PCR based methods are prone to erroneous haplotype or
haplogroup determination due to ambiguous sequence reads, and many of the
resequenced samples had been classified inaccurately. The SNaPshot method applied
with published ancient DNA authenticity criteria is the most straightforward and
cheapest PCR based approach for testing a large number of coding region SNP-s,
which greatly facilitates correct haplogroup determination.
PMID- 28422986
TI - A critical-like collective state leads to long-range cell communication in
Dictyostelium discoideum aggregation.
AB - The transition from single-cell to multicellular behavior is important in early
development but rarely studied. The starvation-induced aggregation of the social
amoeba Dictyostelium discoideum into a multicellular slug is known to result from
single-cell chemotaxis towards emitted pulses of cyclic adenosine monophosphate
(cAMP). However, how exactly do transient, short-range chemical gradients lead to
coherent collective movement at a macroscopic scale? Here, we developed a
multiscale model verified by quantitative microscopy to describe behaviors
ranging widely from chemotaxis and excitability of individual cells to
aggregation of thousands of cells. To better understand the mechanism of long
range cell-cell communication and hence aggregation, we analyzed cell-cell
correlations, showing evidence of self-organization at the onset of aggregation
(as opposed to following a leader cell). Surprisingly, cell collectives, despite
their finite size, show features of criticality known from phase transitions in
physical systems. By comparing wild-type and mutant cells with impaired
aggregation, we found the longest cell-cell communication distance in wild-type
cells, suggesting that criticality provides an adaptive advantage and optimally
sized aggregates for the dispersal of spores.
PMID- 28422988
TI - Rainfall changes affect the algae dominance in tank bromeliad ecosystems.
AB - Climate change and biodiversity loss have been reported as major disturbances in
the biosphere which can trigger changes in the structure and functioning of
natural ecosystems. Nonetheless, empirical studies demonstrating how both factors
interact to affect shifts in aquatic ecosystems are still unexplored. Here, we
experimentally test how changes in rainfall distribution and litter diversity
affect the occurrence of the algae-dominated condition in tank bromeliad
ecosystems. Tank bromeliads are miniature aquatic ecosystems shaped by the
rainwater and allochthonous detritus accumulated in the bases of their leaves.
Here, we demonstrated that changes in the rainfall distribution were able to
reduce the chlorophyll-a concentration in the water of bromeliad tanks affecting
significantly the occurrence of algae-dominated conditions. On the other hand,
litter diversity did not affect the algae dominance irrespective to the rainfall
scenario. We suggest that rainfall changes may compromise important self
reinforcing mechanisms responsible for maintaining high levels of algae on tank
bromeliads ecosystems. We summarized these results into a theoretical model which
suggests that tank bromeliads may show two different regimes, determined by the
bromeliad ability in taking up nutrients from the water and by the total amount
of light entering the tank. We concluded that predicted climate changes might
promote regime shifts in tropical aquatic ecosystems by shaping their structure
and the relative importance of other regulating factors.
PMID- 28422987
TI - Systematic review and meta-analysis shows a specific micronutrient profile in
people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red
blood cell copper and zinc, and higher salivary calcium and sodium.
AB - Different metabolic profiles as well as comorbidities are common in people with
Down Syndrome (DS). Therefore it is relevant to know whether micronutrient levels
in people with DS are also different. This systematic review was designed to
review the literature on micronutrient levels in people with DS compared to age
and sex-matched controls without DS. We identified sixty nine studies from
January 1967 to April 2016 through main electronic medical databases PubMed,
Scopus, and Web of knowledge. We carried out meta-analysis of the data on four
essential trace elements (Cu, Fe, Se, and Zn), six minerals (Ca, Cl, K, Mg, Na,
and P), and five vitamins (vitamin A, B9, B12, D, and E). People with DS showed
lower blood levels of Ca (standard mean difference (SMD) = -0.63; 95% confidence
interval (CI): -1.16 to -0.09), Se (SMD = -0.99; 95% CI: -1.55 to -0.43), and Zn
(SMD = -1.30; 95% CI: -1.75 to -0.84), while red cell levels of Zn (SMD = 1.88;
95% CI: 0.48 to 3.28) and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57) were higher. They
had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33) and Na
(SMD = 1.04; 95% CI: 0.39 to 1.69). Our findings that micronutrient levels are
different in people with DS raise the question whether these differences are
related to the different metabolic profiles, the common comorbidities or merely
reflect DS.
PMID- 28422989
TI - The lack of BTK does not impair monocytes and polymorphonuclear cells functions
in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin
replacement.
AB - The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect
monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this
study, we show that XLA patients had an increased frequency of the intermediate
monocytes subset and that BTK-deficient monocytes and PMN had a normal expression
of receptors involved in the activation and cellular responses. We demonstrate
that BTK is not required for migration, phagocytosis and the production of
reactive oxygen species (ROS) following engagement of FC gamma receptors
(FcgammaR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent
activation of oxidative burst, suggesting that oxidative burst is less dependent
by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered
also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+
mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti
inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In
monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these
functions remained efficient.
PMID- 28422990
TI - Sensory cortical response to uncertainty and low salience during recognition of
affective cues in musical intervals.
AB - Previous neuroimaging studies have shown an increased sensory cortical response
(i.e., heightened weight on sensory evidence) under higher levels of predictive
uncertainty. The signal enhancement theory proposes that attention improves the
quality of the stimulus representation, and therefore reduces uncertainty by
increasing the gain of the sensory signal. The present study employed functional
magnetic resonance imaging (fMRI) to investigate the neural correlates for
ambiguous valence inferences signaled by auditory information within an emotion
recognition paradigm. Participants categorized sound stimuli of three distinct
levels of consonance/dissonance controlled by interval content. Separate
behavioural and neuroscientific experiments were conducted. Behavioural results
revealed that, compared with the consonance condition (perfect fourths, fifths
and octaves) and the strong dissonance condition (minor/major seconds and
tritones), the intermediate dissonance condition (minor thirds) was the most
ambiguous, least salient and more cognitively demanding category (slowest
reaction times). The neuroscientific findings were consistent with a heightened
weight on sensory evidence whilst participants were evaluating intermediate
dissonances, which was reflected in an increased neural response of the right
Heschl's gyrus. The results support previous studies that have observed enhanced
precision of sensory evidence whilst participants attempted to represent and
respond to higher degrees of uncertainty, and converge with evidence showing
preferential processing of complex spectral information in the right primary
auditory cortex. These findings are discussed with respect to music-theoretical
concepts and recent Bayesian models of perception, which have proposed that
attention may heighten the weight of information coming from sensory channels to
stimulate learning about unknown predictive relationships.
PMID- 28422991
TI - Mortality is associated with inflammation, anemia, specific diseases and
treatments, and molecular markers.
AB - Lifespan is a complex trait, and longitudinal data for humans are naturally
scarce. We report the results of Cox regression and Pearson correlation analyses
using data of the Study of Health in Pomerania (SHIP), with mortality data of
1518 participants (113 of which died), over a time span of more than 10 years. We
found that in the Cox regression model based on the Bayesian information
criterion, apart from chronological age of the participant, six baseline
variables were considerably associated with higher mortality rates: smoking, mean
attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration,
albumin/creatinine ratio, treated gastritis, and medication during the last 7
days. Except for smoking, the causative contribution of these variables to
mortality was deemed inconclusive. In turn, four variables were found to be
associated with decreased mortality rates: treatment of benign prostatic
hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being
female was an undisputed causative variable, the causal role of IFG-1 was deemed
inconclusive, and the treatment effects were deemed protective to the degree that
treated subjects feature better survival than respective controls. Using Cox
modeling based on the Akaike information criterion, diabetes, mean corpuscular
hemoglobin concentration, red blood cell count and serum calcium were also
associated with mortality. The latter two, together with albumin and fibrinogen,
aligned with an"integrated albunemia" model of aging proposed recently.
PMID- 28422992
TI - The evolution of cost-efficiency in neural networks during recovery from
traumatic brain injury.
AB - A somewhat perplexing finding in the systems neuroscience has been the
observation that physical injury to neural systems may result in enhanced
functional connectivity (i.e., hyperconnectivity) relative to the typical network
response. The consequences of local or global enhancement of functional
connectivity remain uncertain and this is particularly true for the overall
metabolic cost of the network. We examine the hyperconnectivity hypothesis in a
sample of 14 individuals with TBI with data collected at approximately 3, 6, and
12 months following moderate and severe TBI. As anticipated, individuals with TBI
showed increased network strength and cost early after injury, but by one-year
post injury hyperconnectivity was more circumscribed to frontal DMN and temporal
parietal attentional control regions. Cost in these subregions was a significant
predictor of cognitive performance. Cost-efficiency analysis in the Power 264
data parcellation suggested that at 6 months post injury the network requires
higher cost connections to achieve high efficiency as compared to the network 12
months post injury. These results demonstrate that networks self-organize to re
establish connectivity while balancing cost-efficiency trade-offs.
PMID- 28422993
TI - Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin
autoinflammation.
AB - IL-1beta is a potent player in cutaneous inflammation and central for the
development of a Th17 micro-milieu in autoinflammatory diseases including
psoriasis. Its production is controlled at the transcriptional level and by
subsequent posttranslational processing via inflammatory caspases. In this study,
we detected inflammatory caspase-5 active in epidermal keratinocytes and in
psoriatic skin lesions. Further, interferon-gamma and interleukin-17A
synergistically induced caspase-5 expression in cultured keratinocytes, which was
dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases
relevant triggers for caspase-5 activity and IL-1beta production remain unknown.
Recently, extranuclear DNA has been identified as danger-signals abundant in the
psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded
(ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and
the release of IL-1beta. Further, interleukin-17A promoted caspase-5 function via
facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered
with the IL-1beta release and suppressed caspase-5 in keratinocytes and in
psoriatic skin lesions. Our data link the disease-intrinsic danger signals
psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in psoriasis
providing potential therapeutic targets in Th17-mediated skin autoinflammation.
PMID- 28422994
TI - The Sheep Grimace Scale as an indicator of post-operative distress and pain in
laboratory sheep.
AB - The EU Directive 2010/63/EU changed the requirements regarding the use of
laboratory animals and raised important issues related to assessing the severity
of all procedures undertaken on laboratory animals. However, quantifiable
parameters to assess severity are rare, and improved assessment strategies need
to be developed. Hence, a Sheep Grimace Scale (SGS) was herein established by
observing and interpreting sheep facial expressions as a consequence of pain and
distress following unilateral tibia osteotomy. The animals were clinically
investigated and scored five days before surgery and at 1, 3, 7, 10, 14 and 17
days afterwards. Additionally, cortisol levels in the saliva of the sheep were
determined at the respective time points. For the SGS, video recording was
performed, and pictures of the sheep were randomized and scored by blinded
observers. Osteotomy in sheep resulted in an increased clinical severity score
from days 1 to 17 post-surgery and elevated salivary cortisol levels one day post
surgery. An analysis of facial expressions revealed a significantly increased SGS
on the day of surgery until day 3 post-surgery; this elevated level was sustained
until day 17. Clinical severity and SGS scores correlated positively with a
Pearson's correlation coefficient of 0.47. Further investigations regarding the
applicability of the SGS revealed a high inter-observer reliability with an
intraclass correlation coefficient of 0.92 and an accuracy of 68.2%. In
conclusion, the SGS represents a valuable approach for severity assessment that
may help support and refine a widely used welfare assessment for sheep during
experimental procedures, thereby meeting legislation requirements and minimizing
the occurrence of unrecognized distress in animal experimentation.
PMID- 28422995
TI - Characterization of rotavirus infection in children with acute gastroenteritis in
Bengo province, Northwestern Angola, prior to vaccine introduction.
AB - BACKGROUND: Rotavirus group A (RVA) is considered the leading cause of pediatric
diarrhea, responsible for the high burden of diarrheal diseases in sub-Saharan
Africa. Despite recent studies, the existent data are scarce for some African
countries like Angola, a country with one of the highest RVA-related death
estimates. The aim of this study was to determine the RVA detection rate and
circulating genotypes in children less than five years of age with acute
gastroenteritis attended at the Bengo General Hospital in Caxito, Bengo province,
Angola, before vaccine introduction. METHODS: Between September 2012 and December
2013, 342 fecal specimens were collected from children enrolled. Positive samples
for RVA by immunochromatographic rapid test were G and P-typed by hemi-nested
type-specific multiplex PCR, and subgrouped for the VP6 gene. VP4 and VP7 genes
from a subset of samples were sequenced for phylogenetic analysis. RESULTS:
During the study period, a high RVA detection rate was registered (25.1%,
86/342). The age group most affected by RVA infection includes children under 6
months of age (p<0.01). Vomiting was highly associated with RVA infection (72.1%;
p<0.001). From the 86 RVA-positive samples, 72 (83.7%) were genotyped. The most
prevalent genotype was G1P[8] (34/72; 47.2%), followed by the uncommon G1P[6]
(21/72; 29.2%), and G2P[4] (9/72; 12.5%). Only two G-types were found: G1 (60/72;
83.3%) and G2 (11/72; 15.3%). Among the P-genotypes, P[8] was the most prevalent
(34/72; 47.2%), followed by P[6] (22/72; 30.6%) and P[4] (9/72; 12.5%). In the
phylogenetic trees, the identified G and P-types clustered tightly together and
with reference sequences in specific monophyletic groups, with highly significant
bootstrap values (>=92%). CONCLUSION: This pre-vaccination study revealed, for
the first time for Bengo province (Angola), the RVA genotype profile, including
phylogenetic relationships, and a high RVA detection rate, supporting the
immediate introduction of a RVA vaccine in the national immunization programme.
PMID- 28422996
TI - Overexpression of an EaZIP gene devoid of transit peptide sequence induced leaf
variegation in tobacco.
AB - Leaf variegation is an ornamental trait that is not only biologically but also
economically important. In our previous study, a Mg-protoporphyrin IX monomethyl
ester cyclase homologue, EaZIP (Epipremnum aureum leucine zipper) was found to be
associated with leaf variegation in Epipremnum aureum (Linden & Andre) G.S.
Bunting. The protein product of this nuclear-encoded gene is targeted back to
chloroplast involving in chlorophyll biosynthesis. Based on a web-based homology
analysis, the EaZIP was found to lack a chloroplast transit peptide (cTP)
sequence. In the present study, we tested if overexpression of the EaZIP cDNA
with or without the cTP sequence could affect leaf variegation. Transgenic
tobacco plants overexpressing EaZIP genes with (EaZIPwcTP) and without
(EaZIPwocTP) cTP sequence were generated. Many plant lines harboring EaZIPwocTP
showed variegated leaves, while none of the plant lines with EaZIPwcTP produced
such a phenotype. Molecular analysis of T0 plants and selfed T1 progeny, as well
as observations of tagged marker GFP (green fluorescent protein) did not show any
other difference in patterns of gene integrity and expression. Results from this
study indicate that transgenic approach for expressing EaZIPwocTP could be a
novel method of generating variegated plants even through the underlying
mechanisms remain to be elucidated.
PMID- 28422998
TI - Reducing DNA context dependence in bacterial promoters.
AB - Variation in the DNA sequence upstream of bacterial promoters is known to affect
the expression levels of the products they regulate, sometimes dramatically.
While neutral synthetic insulator sequences have been found to buffer promoters
from upstream DNA context, there are no established methods for designing
effective insulator sequences with predictable effects on expression levels. We
address this problem with Degenerate Insulation Screening (DIS), a novel method
based on a randomized 36-nucleotide insulator library and a simple, high
throughput, flow-cytometry-based screen that randomly samples from a library of
436 potential insulated promoters. The results of this screen can then be
compared against a reference uninsulated device to select a set of insulated
promoters providing a precise level of expression. We verify this method by
insulating the constitutive, inducible, and repressible promotors of a four
transcriptional-unit inverter (NOT-gate) circuit, finding both that order
dependence is largely eliminated by insulation and that circuit performance is
also significantly improved, with a 5.8-fold mean improvement in on/off ratio.
PMID- 28422997
TI - Promoter hypermethylation as a mechanism for Lamin A/C silencing in a subset of
neuroblastoma cells.
AB - Nuclear lamins support the nuclear envelope and provide anchorage sites for
chromatin. They are involved in DNA synthesis, transcription, and replication. It
has previously been reported that the lack of Lamin A/C expression in lymphoma
and leukaemia is due to CpG island promoter hypermethylation. Here, we provide
evidence that Lamin A/C is silenced via this mechanism in a subset of
neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a
demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth
kinetics and impaired migration, invasion, and anchorage-independent cell growth.
Cytoskeletal restructuring was also induced. In addition, the introduction of
lamin Delta50, known as Progerin, caused senescence in these neuroblastoma cells.
These cells were stiffer and developed a cytoskeletal structure that differed
from that observed upon Lamin A/C introduction. Of relevance, short hairpin RNA
Lamin A/C depletion in unmethylated neuroblastoma cells enhanced the
aforementioned tumour properties. A cytoskeletal structure similar to that
observed in methylated cells was induced. Furthermore, atomic force microscopy
revealed that Lamin A/C knockdown decreased cellular stiffness in the lamellar
region. Finally, the bioinformatic analysis of a set of methylation arrays of
neuroblastoma primary tumours showed that a group of patients (around 3%) gives a
methylation signal in some of the CpG sites located within the Lamin A/C promoter
region analysed by bisulphite sequencing PCR. These findings highlight the
importance of Lamin A/C epigenetic inactivation for a subset of neuroblastomas,
leading to enhanced tumour properties and cytoskeletal changes. Additionally,
these findings may have treatment implications because tumour cells lacking Lamin
A/C exhibit more aggressive behaviour.
PMID- 28422999
TI - Zooming in: From spatially extended traveling waves to localized structures: The
case of the Sine-Gordon equation in (1+3) dimensions.
AB - The Sine-Gordon equation in (1+3) dimensions has N-traveling front ("kink",
"domain wall")- solutions for all N >= 1. A nonlinear functional of the solution,
which vanishes on a single-front, maps multi-front solutions onto sets of
infinitely long, but laterally bounded, rods, which move in space. Each rod is
localized in the vicinity of the intersection of two Sine-Gordon fronts. The rod
systems are solutions of the linear wave equation, driven by a term that is
constructed out of Sine-Gordon fronts. An additional linear operation maps multi
rod systems onto sets of blobs. Each blob is localized in the vicinity of rod
intersection, and moves in space. The blob systems are solutions of the linear
wave equation, driven by a term that is also constructed out of Sine-Gordon
fronts. The temporal evolution of multi-blob solutions mimics elastic collisions
of systems of spatially extended particles.
PMID- 28423000
TI - Inbreeding and selection shape genomic diversity in captive populations:
Implications for the conservation of endangered species.
AB - Captive breeding programs are often initiated to prevent species extinction until
reintroduction into the wild can occur. However, the evolution of captive
populations via inbreeding, drift, and selection can impair fitness, compromising
reintroduction programs. To better understand the evolutionary response of
species bred in captivity, we used nearly 5500 single nucleotide polymorphisms
(SNPs) in populations of white-footed mice (Peromyscus leucopus) to measure the
impact of breeding regimes on genomic diversity. We bred mice in captivity for 20
generations using two replicates of three protocols: random mating (RAN),
selection for docile behaviors (DOC), and minimizing mean kinship (MK). The MK
protocol most effectively retained genomic diversity and reduced the effects of
selection. Additionally, genomic diversity was significantly related to fitness,
as assessed with pedigrees and SNPs supported with genomic sequence data. Because
captive-born individuals are often less fit in wild settings compared to wild
born individuals, captive-estimated fitness correlations likely underestimate the
effects in wild populations. Therefore, minimizing inbreeding and selection in
captive populations is critical to increasing the probability of releasing fit
individuals into the wild.
PMID- 28423001
TI - Pre-hatching embryo-dependent and -independent programming of endometrial
function in cattle.
AB - The bovine pre-implantation embryo secretes bioactive molecules from early
development stages, but effects on endometrial function are reported to start
only after elongation. Here, we interrogated spatially defined regions of the
endometrium transcriptome for responses to a day 7 embryo in vivo. We hypothesize
that exposure to an embryo changes the abundance of specific transcripts in the
cranial region of the pregnant uterine horn. Endometrium was collected from the
uterotubal junction (UTJ), anterior (IA), medial (IM) and posterior (IP) regions
of the uterine horn ipsilateral to the CL 7 days after estrus from sham
inseminated (Con) or artificially inseminated, confirmed pregnant (Preg) cows.
Abundance of 86 transcripts was evaluated by qPCR using a microfluidic platform.
Abundance of 12 transcripts was modulated in the Preg endometrium, including
classical interferon-stimulated genes (ISG15, MX1, MX2 and OAS1Y), prostaglandin
biosynthesis genes (PTGES, HPGD and AKR1C4), water channel (AQP4) and a solute
transporter (SLC1A4) and this was in the UTJ and IA mainly. Additionally, for 71
transcripts, abundance varied according to region of the reproductive tract.
Regulation included downregulation of genes associated with proliferation (IGF1,
IGF2, IGF1R and IGF2R) and extracellular matrix remodeling (MMP14, MMP19 and
MMP2) and upregulation of anti-adhesive genes (MUC1) in the cranial regions of
uterine horn. Physical proximity to the embryo provides paracrine regulation of
endometrial function. Embryo-independent regulation of the endometrial
transcriptome may support subsequent stages of embryo development, such as
elongation and implantation. We speculate that successful early embryo-dependent
and -independent programming fine-tune endometrial functions that are important
for maintenance of pregnancy in cattle.
PMID- 28423002
TI - Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory
signaling in vitro and in vivo.
AB - Serum amyloid A (SAA) is an acute phase protein with cytokine-like and
chemotactic properties, that is markedly up-regulated during various inflammatory
conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B
scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This
study provides new evidence that SR-BII, splice variant of SR-BI, could function
as an SAA receptor mediating its uptake and pro-inflammatory signaling. The
uptake of Alexa Fluor488 SAA was markedly (~3 fold) increased in hSR-BII
expressing HeLa cells when compared with mock-transfected cells. The levels of
SAA-induced interleukin-8 secretion by hSR-BII-expressing HEK293 cells were also
significantly (~3-3.5 fold) higher than those detected in control cells.
Moderately enhanced levels of phosphorylation of all three mitogen-activated
protein kinases, ERK1/2, and p38 and JNK, were observed in hSR-BII-expressing
cells following SAA stimulation when compared with control wild type cells.
Transgenic mice with pLiv-11-directed liver/kidney overexpression of hSR-BI or
hSR-BII were used to assess the in vivo role of each receptor in SAA-induced pro
inflammatory response in these organs. Six hours after intraperitoneal SAA
injection both groups of transgenic mice demonstrated markedly higher (~2-5-fold)
expression levels of inflammatory mediators in the liver and kidney compared to
wild type mice. Histological examinations of hepatic and renal tissue from SAA
treated mice revealed moderate level of damage in the liver of both transgenic
but not in the wild type mice. Activities of plasma transaminases, biomarkers of
liver injury, were also moderately higher in hSR-B transgenic mice when compared
to wild type mice. Our findings identify hSR-BII as a functional SAA receptor
that mediates SAA uptake and contributes to its pro-inflammatory signaling via
the MAPKs-mediated signaling pathways.
PMID- 28423003
TI - HacDivSel: Two new methods (haplotype-based and outlier-based) for the detection
of divergent selection in pairs of populations.
AB - The detection of genomic regions involved in local adaptation is an important
topic in current population genetics. There are several detection strategies
available depending on the kind of genetic and demographic information at hand. A
common drawback is the high risk of false positives. In this study we introduce
two complementary methods for the detection of divergent selection from
populations connected by migration. Both methods have been developed with the aim
of being robust to false positives. The first method combines haplotype
information with inter-population differentiation (FST). Evidence of divergent
selection is concluded only when both the haplotype pattern and the FST value
support it. The second method is developed for independently segregating markers
i.e. there is no haplotype information. In this case, the power to detect
selection is attained by developing a new outlier test based on detecting a
bimodal distribution. The test computes the FST outliers and then assumes that
those of interest would have a different mode. We demonstrate the utility of the
two methods through simulations and the analysis of real data. The simulation
results showed power ranging from 60-95% in several of the scenarios whilst the
false positive rate was controlled below the nominal level. The analysis of real
samples consisted of phased data from the HapMap project and unphased data from
intertidal marine snail ecotypes. The results illustrate that the proposed
methods could be useful for detecting locally adapted polymorphisms. The software
HacDivSel implements the methods explained in this manuscript.
PMID- 28423004
TI - Variations in the interaction of human defensins with Escherichia coli: Possible
implications in bacterial killing.
AB - Human alpha and beta-defensins are cationic antimicrobial peptides characterized
by three disulfide bonds with a triple stranded beta-sheet motif. It is presumed
that interaction with the bacterial cell surface and membrane permeabilization by
defensins is an important step in the killing process. In this study, we have
compared interactions of three human alpha-defensins HNP3, HNP4, HD5 and human
beta-defensins HBD1-4 that are active against Escherichia coli, with its cell
surface and inner membrane as well as negatively charged model membranes. We have
also included the inactive alpha-defensin HD6 in the study. Among the alpha
defensins, HNP4, HD5 and HD6 were more effective in increasing the zeta potential
as compared to HNP3. Among the beta-defensins, HBD1 was the least effective in
increasing the zeta potential. The zeta potential modulation data indicate
variations in the surface charge neutralizing ability of alpha- and beta
defensins. Comparison of E. coli inner membrane and model membrane permeabilizing
abilities indicated that HD5, HD6 and HBD1 do not permeabilize membranes.
Although HBD4 does not permeabilize model membranes, considerable damage to the
inner membrane of E. coli is observed. Our data indicate that mammalian defensins
do not kill E. coli by a simple mechanism involving membrane permeabilization
though their antibacterial potencies are very similar.
PMID- 28423005
TI - An archosauromorph dominated ichnoassemblage in fluvial settings from the late
Early Triassic of the Catalan Pyrenees (NE Iberian Peninsula).
AB - The vertebrate recovery after the end-Permian mass extinction can be approached
through the ichnological record, which is much more abundant than body fossils.
The late Olenekian (Early Triassic) tetrapod ichnoassemblage of the Catalan
Pyrenean Basin is the most complete and diverse of this age from Western Tethys.
This extensional basin, composed of several depocenters, was formed in the latest
phases of the Variscan orogeny (Pangea breakup) and was infilled by braided and
meandering fluvial systems of the red-beds Buntsandstein facies. Abundant and
diverse tetrapod ichnites are recorded in these facies, including Prorotodactylus
mesaxonichnus isp. nov. (tracks possibly produced by euparkeriids), cf.
Rotodactylus, at least two large chirotheriid morphotypes (archosauriform
trackmakers), Rhynchosauroides cf. schochardti, two other undetermined
Rhynchosauroides forms, an undetermined Morphotype A (archosauromorph
trackmakers) and two types of Characichnos isp. (swimming traces, here associated
to archosauromorph trackmakers). The Pyrenean ichnoassemblage suggests a
relatively homogeneous ichnofaunal composition through the late Early Triassic of
Central Pangea, characterized by the presence of Prorotodactylus and
Rotodactylus. Small archosauromorph tracks dominate and present a wide
distribution through the different fluviatile facies of the Triassic Pyrenean
Basin, with large archosaurian footprints being present in a lesser degree.
Archosauromorphs radiated and diversified through the Triassic vertebrate
recovery, which ultimately lead to the archosaur and dinosaur dominance of the
Mesozoic.
PMID- 28423006
TI - Transcriptome and proteome responses in RNAlater preserved tissue of Arabidopsis
thaliana.
AB - Tissue preservation is a minimal requirement for the success of plant RNA and
protein expression studies. The standard of snap-freezing in liquid nitrogen is
not always practical or possible. RNAlater, a concentrated solution of ammonium
and cesium sulfates, has become a standard preservative in the absence of liquid
nitrogen. Here, we demonstrate the effectiveness of RNAlater in preserving both
RNA and proteins in Arabidopsis thaliana tissues for use in RNAseq and LC-MS/MS
analysis of proteins. While successful in preserving plant material, a
transcriptomic and proteomic response is evident. Specifically, 5770 gene
transcripts, 84 soluble proteins, and 120 membrane-bound proteins were found to
be differentially expressed at a log-fold change of +/-1 (P <= 0.05). This
response is mirrored in the abundance of post-translational modifications, with
23 of the 108 (21.3%) phosphorylated proteins showing altered abundance at a log
fold change of +/-1 (P <= 0.05). While RNAlater is effective in preserving
biological information, our findings warrant caution in its use for
transcriptomic and proteomic experiments.
PMID- 28423007
TI - Recombinants from the crosses between amphidiploid and cultivated peanut (Arachis
hypogaea) for pest-resistance breeding programs.
AB - Peanut is a major oilseed crop worldwide. In the Brazilian peanut production,
silvering thrips and red necked peanut worm are the most threatening pests.
Resistant varieties are considered an alternative to pest control. Many wild
diploid Arachis species have shown resistance to these pests, and these can be
used in peanut breeding by obtaining hybrid of A and B genomes and subsequent
polyploidization with colchicine, resulting in an AABB amphidiploid. This
amphidiploid can be crossed with cultivated peanut (AABB) to provide genes of
interest to the cultivar. In this study, the sterile diploid hybrids from A.
magna V 13751 and A. kempff-mercadoi V 13250 were treated with colchicine for
polyploidization, and the amphidiploids were crossed with A. hypogaea cv. IAC OL
4 to initiate the introgression of the wild genes into the cultivated peanut. The
confirmation of the hybridity of the progenies was obtained by: (1) reproductive
characterization through viability of pollen, (2) molecular characterization
using microsatellite markers and (3) morphological characterization using 61
morphological traits with principal component analysis. The diploid hybrid
individual was polyploidized, generating the amphidiploid An 13 (A. magna V 13751
x A. kempff-mercadoi V 13250)4x. Four F1 hybrid plants were obtained from IAC OL
4 * An 13, and 51 F2 seeds were obtained from these F1 plants. Using
reproductive, molecular and morphological characterizations, it was possible to
distinguish hybrid plants from selfed plants. In the cross between A. hypogaea
and the amphidiploid, as the two parents are polyploid, the hybrid progeny and
selves had the viability of the pollen grains as high as the parents. This fact
turns the use of reproductive characteristics impossible for discriminating, in
this case, the hybrid individuals from selfing. The hybrids between A. hypogaea
and An 13 will be used in breeding programs seeking pest resistance, being
subjected to successive backcrosses until recovering all traits of interest of A.
hypogaea, keeping the pest resistance.
PMID- 28423008
TI - Perirenal fat thickness measured with computed tomography is a reliable estimate
of perirenal fat mass.
AB - Deposition of perirenal adipose tissue has been associated with adverse renal and
cardiovascular events. We compared various methods to measure perirenal adipose
tissue using computerized tomography (CT)-scan and performed correlations with
anthropometric measures associated with renal and cardiovascular events.
Voluntary overweight and obese subjects undergoing a CT-scan for diagnostic
purposes were included in the study. Perirenal adipose tissue volume, adipose
tissue area of the renal sinus and perirenal fat thickness were manually measured
bilaterally. The intra- and inter-observer coefficient correlations and the
correlation between the diverse measures of renal adipose tissue, subcutaneous
(SC-)fat and anthropometrics measures were analyzed using Pearson's correlation
tests. The forty included patients (24 men, 16 women) had a mean age of 57.6 +/-
18.1 years and a mean body mass index of 28.9 +/- 2.9 kg/m2. Despite comparable
waist circumference, women had a greater SC-fat thickness compared to men, and
therefore a smaller amount of visceral fat, as well as smaller perirenal fat
volumes. Perirenal fat thickness was better correlated with perirenal fat volume
than adipose area of the renal sinus (p <0.02). The adipose area of the renal
sinus did not correlate with any anthropometric measures. In women, perirenal fat
volume and thickness showed a negative correlation with SC-fat thickness and no
correlation with waist circumference. In men, perirenal fat volume and thickness
showed a positive correlation with waist circumference and no correlation with
subcutaneous fat thickness. In conclusion, perirenal fat thickness measured with
CT-scan at the level of the renal veins is a simple and reliable estimate of
perirenal fat volume, that correlated negatively with SC-fat in women and
positively with waist circumference in men. The adipose area of the renal sinus
did not correlate with any anthropometric measure.
PMID- 28423009
TI - Correction: Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2
Concentrations Are Related to Renal Function in Two Population-Based Cohorts.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166492.].
PMID- 28423010
TI - Correction: The H3K27 demethylase, Utx, regulates adipogenesis in a
differentiation stage-dependent manner.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173713.].
PMID- 28423011
TI - The range of the mange: Spatiotemporal patterns of sarcoptic mange in red foxes
(Vulpes vulpes) as revealed by camera trapping.
AB - Sarcoptic mange is a widely distributed disease that affects numerous mammalian
species. We used camera traps to investigate the apparent prevalence and
spatiotemporal dynamics of sarcoptic mange in a red fox population in
southeastern Norway. We monitored red foxes for five years using 305 camera traps
distributed across an 18000 km2 area. A total of 6581 fox events were examined to
visually identify mange compatible lesions. We investigated factors associated
with the occurrence of mange by using logistic models within a Bayesian
framework, whereas the spatiotemporal dynamics of the disease were analysed with
space-time scan statistics. The apparent prevalence of the disease fluctuated
over the study period with a mean of 3.15% and credible interval [1.25, 6.37],
and our best logistic model explaining the presence of red foxes with mange
compatible lesions included time since the beginning of the study and the
interaction between distance to settlement and season as explanatory variables.
The scan analyses detected several potential clusters of the disease that varied
in persistence and size, and the locations in the cluster with the highest
probability were closer to human settlements than the other survey locations. Our
results indicate that red foxes in an advanced stage of the disease are most
likely found closer to human settlements during periods of low wild prey
availability (winter). We discuss different potential causes. Furthermore, the
disease appears to follow a pattern of small localized outbreaks rather than
sporadic isolated events.
PMID- 28423012
TI - 15-hydroxyprostaglandin dehydrogenase (15-PGDH) prevents lipopolysaccharide (LPS)
induced acute liver injury.
AB - The NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the
oxidation of the 15(S)-hydroxyl group of prostaglandin E2 (PGE2), converting the
pro-inflammatory PGE2 to the anti-inflammatory 15-keto-PGE2 (an endogenous ligand
for peroxisome proliferator-activated receptor-gamma [PPAR-gamma]). To evaluate
the significance of 15-PGDH/15-keto-PGE2 cascade in liver inflammation and tissue
injury, we generated transgenic mice with targeted expression of 15-PGDH in the
liver (15-PGDH Tg) and the animals were subjected to lipopolysaccharide
(LPS)/Galactosamine (GalN)-induced acute liver inflammation and injury. Compared
to the wild type mice, the 15-PGDH Tg mice showed lower levels of alanine
aminotransferase (ALT) and aspartate aminotransferase (AST), less liver tissue
damage, less hepatic apoptosis/necrosis, less macrophage activation, and lower
inflammatory cytokine production. In cultured Kupffer cells, treatment with 15
keto-PGE2 or the conditioned medium (CM) from 15-PGDH Tg hepatocyes inhibited LPS
induced cytokine production, in vitro. Both 15-keto-PGE2 and the CM from15-PGDH
Tg hepatocyes also up-regulated the expression of PPAR-gamma downstream genes in
Kupffer cells. In cultured hepatocytes, 15-keto-PGE2 treatment or 15-PGDH
overexpression did not influence TNF-alpha-induced hepatocyte apoptosis. These
findings suggest that 15-PGDH protects against LPS/GalN-induced liver injury and
the effect is mediated via 15-keto-PGE2, which activates PPAR-gamma in Kupffer
cells and thus inhibits their ability to produce inflammatory cytokines.
Accordingly, we observed that the PPAR-gamma antagonist, GW9662, reversed the
effect of 15-keto-PGE2 in Kupffer cell in vitro and restored the susceptibility
of 15-PGDH Tg mice to LPS/GalN-induced acute liver injury in vivo. Collectively,
our findings suggest that 15-PGDH-derived 15-keto-PGE2 from hepatocytes is able
to activate PPAR-gamma and inhibit inflammatory cytokine production in Kupffer
cells and that this paracrine mechanism negatively regulates LPS-induced necro
inflammatory response in the liver. Therefore, induction of 15-PGDH expression or
utilization of 15-keto-PGE2 analogue may have therapeutic benefits for the
treatment of endotoxin-associated liver inflammation/injury.
PMID- 28423014
TI - Initial systemic inflammatory state perturbs exercise training adaptations in
elite Taekwondo athletes.
AB - PURPOSE: This study examined ten-week TKD-specific training effects on aerobic
capacity, body composition, hormone responses and hematological parameters in
elite TKD athletes with varied initial inflammatory states. METHODS: Twenty-two
elite college TKD athletes were divided into two groups according to their
initial neutrophils-to-lymphocytes ratio (NLR) values: Low NLR (N = 11, 9M/2F,
age: 21.6 +/- 1.0 yrs; NLR: 1.3 +/- 0.2) and High NLR (N = 11, 8M/3F, age: 22.0
+/- 0.7 yrs, NLR: 2.5 +/- 1.3), and participated in a 10-week TKD-specific
training program. Aerobic capacity, body composition, hormonal responses and
hematological parameters were measured at baseline and 10-weeks after TKD
training. RESULTS: VO2max and shuttle run distance were significantly increased
in both groups after training. However, the degree of improvement was greater in
the Low NLR group than in the High NLR group. After 10-weeks of exercise
training, the High NLR group presented markedly higher fat mass percentage and
visceral fat area and significantly lowers DHEA-S to cortisol ratio (D/C ratio)
than the Low NRL group. The post-training NLR was negatively correlated with the
D/C ratio. Neutrophil counts and NLR were still significantly higher in the High
NLR group after training. CONCLUSIONS: This study provides new evidence that
young elite TKD athletes with slightly high baseline systemic inflammatory state
appear to perturb adaptations to exercise training.
PMID- 28423013
TI - Mapping the co-localization of the circadian proteins PER2 and BMAL1 with
enkephalin and substance P throughout the rodent forebrain.
AB - Despite rhythmic expression of clock genes being found throughout the central
nervous system, very little is known about their function outside of the
suprachiasmatic nucleus. Determining the pattern of clock gene expression across
neuronal subpopulations is a key step in understanding their regulation and how
they may influence the functions of various brain structures. Using
immunofluorescence and confocal microscopy, we quantified the co-expression of
the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and
Enkephalin (Enk), expressed in distinct neuronal populations throughout the
forebrain. Regions examined included the limbic forebrain (dorsal striatum,
nucleus accumbens, amygdala, stria terminalis), thalamus medial habenula of the
thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the
olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in
nearly all neurons (~90%), and PER2 was expressed in a slightly lower proportion
of cells. There was no specific correlation to SubP- or Enk- expressing
subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were
expressed in a much smaller percentage of cells, and Enk was rarely found in the
same cells that expressed the clock proteins (SubP was undetectable). These
results indicate that clock genes are not unique to specific cell types, and
further studies will be required to determine the factors that contribute to the
regulation of clock gene expression throughout the brain.
PMID- 28423015
TI - Correction: 16 Weeks of Progressive Barefoot Running Training Changes Impact
Force and Muscle Activation in Habitual Shod Runners.
AB - [This corrects the article DOI: 10.1371/journal.pone.0167234.].
PMID- 28423016
TI - Evaluating the utility of two gestural discomfort evaluation methods.
AB - Evaluating physical discomfort of designed gestures is important for creating
safe and usable gesture-based interaction systems; yet, gestural discomfort
evaluation has not been extensively studied in HCI, and few evaluation methods
seem currently available whose utility has been experimentally confirmed. To
address this, this study empirically demonstrated the utility of the subjective
rating method after a small number of gesture repetitions (a maximum of four
repetitions) in evaluating designed gestures in terms of physical discomfort
resulting from prolonged, repetitive gesture use. The subjective rating method
has been widely used in previous gesture studies but without empirical evidence
on its utility. This study also proposed a gesture discomfort evaluation method
based on an existing ergonomics posture evaluation tool (Rapid Upper Limb
Assessment) and demonstrated its utility in evaluating designed gestures in terms
of physical discomfort resulting from prolonged, repetitive gesture use. Rapid
Upper Limb Assessment is an ergonomics postural analysis tool that quantifies the
work-related musculoskeletal disorders risks for manual tasks, and has been
hypothesized to be capable of correctly determining discomfort resulting from
prolonged, repetitive gesture use. The two methods were evaluated through
comparisons against a baseline method involving discomfort rating after actual
prolonged, repetitive gesture use. Correlation analyses indicated that both
methods were in good agreement with the baseline. The methods proposed in this
study seem useful for predicting discomfort resulting from prolonged, repetitive
gesture use, and are expected to help interaction designers create safe and
usable gesture-based interaction systems.
PMID- 28423017
TI - Auxotonic to isometric contraction transitioning in a beating heart causes myosin
step-size to down shift.
AB - Myosin motors in cardiac ventriculum convert ATP free energy to the work of
moving blood volume under pressure. The actin bound motor cyclically rotates its
lever-arm/light-chain complex linking motor generated torque to the myosin
filament backbone and translating actin against resisting force. Previous
research showed that the unloaded in vitro motor is described with high precision
by single molecule mechanical characteristics including unitary step-sizes of
approximately 3, 5, and 8 nm and their relative step-frequencies of approximately
13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin
essential light chain (ELC) N-terminus actin binding. Step-size and step
frequency quantitation specifies in vitro motor function including duty-ratio,
power, and strain sensitivity metrics. In vivo, motors integrated into the muscle
sarcomere form the more complex and hierarchically functioning muscle machine.
The goal of the research reported here is to measure single myosin step-size and
step-frequency in vivo to assess how tissue integration impacts motor function. A
photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in
the beating heart of a live zebrafish embryo. Detected single GFP emission
reports time-resolved myosin lever-arm orientation interpreted as step-size and
step-frequency providing single myosin mechanical characteristics over the active
cycle. Following step-frequency of cardiac ventriculum myosin transitioning from
low to high force in relaxed to auxotonic to isometric contraction phases
indicates that the imposition of resisting force during contraction causes the
motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in
the near-isometric phase. At peak force, the ATP initiated actomyosin
dissociation is the predominant strain inhibited transition in the native myosin
contraction cycle. The proposed model for motor down-shifting and strain sensing
involves ELC N-terminus actin binding. Overall, the approach is a unique bottom
up single molecule mechanical characterization of a hierarchically functional
native muscle myosin.
PMID- 28423018
TI - Comprehensive analysis of phospholipids and glycolipids in the opportunistic
pathogen Enterococcus faecalis.
AB - Enterococcus faecalis is a Gram-positive, opportunistic, pathogenic bacterium
that causes a significant number of antibiotic-resistant infections in
hospitalized patients. The development of antibiotic resistance in hospital
associated pathogens is a formidable public health threat. In E. faecalis and
other Gram-positive pathogens, correlations exist between lipid composition and
antibiotic resistance. Resistance to the last-resort antibiotic daptomycin is
accompanied by a decrease in phosphatidylglycerol (PG) levels, whereas multiple
peptide resistance factor (MprF) converts anionic PG into cationic lysyl-PG via a
trans-esterification reaction, providing resistance to cationic antimicrobial
peptides. Unlike previous studies that relied on thin layer chromatography and
spectrophotometry, we have performed liquid chromatography-tandem mass
spectrometry (LC-MS/MS) directly on lipids extracted from E. faecalis, and
quantified the phospholipids through multiple reaction monitoring (MRM). In the
daptomycin-sensitive E. faecalis strain OG1RF, we have identified 17 PGs, 8 lysyl
PGs (LPGs), 23 cardiolipins (CL), 3 glycerophospho-diglucosyl-diacylglycerols
(GPDGDAG), 5 diglucosyl-diacylglycerols (DGDAG), 3 diacylglycerols (DAGs), and 4
triacylglycerols (TAGs). We have quantified PG and shown that PG levels vary
during growth of E. faecalis in vitro. We also show that two daptomycin-resistant
(DapR) strains of E. faecalis have substantially lower levels of PG and LPG
levels. Since LPG levels in these strains are lower, daptomycin resistance is
likely due to the reduction in PG. This lipidome map is the first comprehensive
analysis of membrane phospholipids and glycolipids in the important human
pathogen E. faecalis, for which antimicrobial resistance and altered lipid
homeostasis have been intimately linked.
PMID- 28423019
TI - Design, synthesis and structure-activity relationship study of wollamide B; a new
potential anti TB agent.
AB - Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits
activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 MUM). Aiming to
define its structural activity relationship (SAR), optimizing potency and
pharmacokinetic properties, libraries of analogues were synthesized following a
standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial
activities of wollamide B and all the synthesized analogues were tested against
Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and
pharmacokinetic (ADME) profiling was done for the synthesized compounds to
evaluate their drug likeness. Among the 25 synthesized wollamides five of them
showed potent activities with MICs <= 3.1 MUM and found to be nontoxic against
human HepG2 cells up to 100 MUM. The results of the in vitro ADME profiling
revealed the remarkable plasma stability and very good aqueous solubility of the
class in general while the metabolic stability was found to be moderate to low.
Of particular note, compounds 7c (MIC = 1.1 MUM) and 13c (0.6 MUM) that exhibited
good balance of antimycobacterial activity vs. optimal pharmacokinetic properties
could be used as a new lead for further development.
PMID- 28423020
TI - Refractive error change and vision improvement in moderate to severe hyperopic
amblyopia after spectacle correction: Restarting the emmetropization process?
AB - PURPOSE: The aims of the study were to develop guidelines for prescribing
spectacles for patients with moderate to severe hyperopic amblyopia and to
demonstrate how emmetropization progresses. METHODS: Children with hyperopic
amblyopia who had a spherical equivalent of >= +4.0 diopters (D) or more were
included, while those who had astigmatism of > 2.0 D or anisometropia of > 2.0 D
were excluded. The patients were divided into a full correction group and an
under-correction group according to the amount of hyperopia correction applied.
The under-correction group was further subdivided into a fixed under-correction
group and a post-cycloplegic refraction (PCR) under-correction group. The
duration of amblyopia treatment and changes in initial hyperopia were compared
between the groups. RESULTS: In total, 76 eyes of 38 patients were analyzed in
this study. The full correction group and under-correction group were subjected
to 5.5 months and 5.9 months of amblyopia treatment, respectively (P = 0.570).
However, the PCR under-correction group showed more rapid improvement (2.9
months; P = 0.001). In the under-correction group, initial hyperopia was
decreased by -0.28 D and -0.49 D at 6 months and 12 months, respectively, after
initial cycloplegic refraction. Moreover, the amount of hyperopia under
correction was correlated with the amount of hyperopia reduction (P = 0.010).
CONCLUSION: The under-correction of moderate to severe hyperopic amblyopia has
beneficial effects for treating amblyopia and activating emmetropization. PCR
under-correction can more rapidly improve visual acuity, while both fixed under
correction and PCR under-correction can induce emmetropization and effectively
reduce initial hyperopia.
PMID- 28423021
TI - Trait impulsivity components correlate differently with proactive and reactive
control.
AB - The relationship between impulsivity and cognitive control is still unknown. We
hypothesized that trait impulsivity would differentially correlate with specific
cognitive control processes. Trait impulsivity was measured by the Barratt
Impulsiveness Scale, which assesses motor, attention, and non-planning
impulsiveness components. Cognitive control was measured by a hybrid-designed
Stroop task, which distinguishes proactive and reactive control. Thirty-three
participants performed the Stroop task while they were scanned by functional
magnetic resonance imaging. Proactive and reactive control involved increased
activity in the fronto-parietal network, and brain activity was associated with
impulsivity scores. Specifically, higher motor impulsiveness was associated with
a larger proactive control effect in the inferior parietal lobule and a smaller
reactive control effect in the right dorsolateral prefrontal cortex (DLPFC) and
anterior cingulate contex. Higher attention impulsivity was associated with a
smaller proactive control effect in the right DLPFC. Such a correlation pattern
suggests that impulsivity trait components are attributable to different
cognitive control subsystems.
PMID- 28423022
TI - Bioactivity and structure-activity relationship of cinnamic acid esters and their
derivatives as potential antifungal agents for plant protection.
AB - A series of cinnamic acid esters and their derivatives were synthesized and
evaluated for antifungal activities in vitro against four plant pathogenic fungi
by using the mycelium growth rate method. Structure-activity relationship was
derived also. Almost all of the compounds showed some inhibition activity on each
of the fungi at 0.5 mM. Eight compounds showed the higher average activity with
average EC50 values of 17.4-28.6 MUg/mL for the fungi than kresoxim-methyl, a
commercial fungicide standard, and ten compounds were much more active than
commercial fungicide standards carbendazim against P. grisea or kresoxim-methyl
against both P. grisea and Valsa mali. Compounds C1 and C2 showed the higher
activity with average EC50 values of 17.4 and 18.5 MUg/mL and great potential for
development of new plant antifungal agents. The structure-activity relationship
analysis showed that both the substitution pattern of the phenyl ring and the
alkyl group in the alcohol moiety significantly influences the activity. There
exists complexly comprehensive effect between the substituents on the phenyl ring
and the alkyl group in the alcohol moiety on the activity. Thus, cinnamic acid
esters showed great potential the development of new antifungal agents for plant
protection due to high activity, natural compounds or natural compound framework,
simple structure, easy preparation, low-cost and environmentally friendly.
PMID- 28423023
TI - Nanoscale modifications in the early heating stages of bone are heterogeneous at
the microstructural scale.
AB - Nanoscale studies of bone provide key indicators to evidence subtle structural
changes that may occur in the biomedical, forensic and archaeological contexts.
One specific problem encountered in all those disciplines, for which the
identification of nanostructural cues could prove useful, is to properly monitor
the effect of heating on bone tissue. In particular, the mechanisms at work at
the onset of heating are still relatively unclear. Using a multiscale approach
combining Raman microspectroscopy, transmission electron microscopy (TEM),
synchrotron quantitative scanning small-angle X-ray scattering imaging (qsSAXSI)
and polarized light (PL) microscopy, we investigate the ultrastructure of
cortical bovine bone heated at temperatures < 300 degrees C, from the molecular
to the macroscopic scale. We show that, despite limited changes in crystal
structure, the mineral nanoparticles increase in thickness and become strongly
disorganized upon heating. Furthermore, while the nanostructure in distinct
anatomical quadrants appears to be statistically different, our results
demonstrate this stems from the tissue histology, i.e. from the high degree of
heterogeneity of the microstructure induced by the complex cellular processes
involved in bone tissue formation. From this study, we conclude that the analysis
of bone samples based on the structure and organization of the mineral
nanocrystals requires performing measurements at the histological level, which is
an advantageous feature of qsSAXSI. This is a critical aspect that extends to a
much broader range of questions relating to nanoscale investigations of bone,
which could also be extended to other classes of nanostructured heterogeneous
materials.
PMID- 28423024
TI - Interrelationships of VEL1 and ENV1 in light response and development in
Trichoderma reesei.
AB - Sexual development is regulated by a complex regulatory mechanism in fungi. For
Trichoderma reesei, the light response pathway was shown to impact sexual
development, particularly through the photoreceptor ENVOY. Moreover, T. reesei
communicates chemically with a potential mating partner in its vicinity, a
response which is mediated by the velvet family protein VEL1 and its impact on
secondary metabolism. We therefore studied the regulatory interactions of ENV1
and VEL1 with a focus on sexual development. Although individual mutants in both
genes are female sterile under standard crossing conditions (light-dark cycles),
an altered light regime enabled sexual development, which we found to be due to
conditional female sterility of Deltaenv1, but not Deltavel1. Phenotypes of
growth and asexual sporulation as well as regulation of the peptide pheromone
precursors of double mutants suggested that ENV1 and VEL1 balance positive and
negative regulators of these functions. Additionally, VEL1 contributed to the
strong deregulation of the pheromone system observed in env1 mutants. Female
sterility of Deltavel1 was rescued by deletion of env1 in darkness in MAT1-1,
indicating a block of sexual development by ENV1 in darkness that is balanced by
VEL1 in the wild-type. We conclude that ENV1 and VEL1 exert complementing
functions in development of T. reesei. Our results further showed that the
different developmental phenotypes of vel1/veA mutants in T. reesei and
Aspergillus nidulans are not due to the presence or function of ENV1 in the
VELVET regulatory pathway in T. reesei.
PMID- 28423025
TI - Determination of influenza B identity and potency in quadrivalent inactivated
influenza vaccines using lineage-specific monoclonal antibodies.
AB - Co-circulation of two antigenically and genetically distinct lineages of
influenza B virus, represented by prototype viruses B/Victoria/2/1987 and
B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines
that contain two influenza B antigens. The inclusion of two influenza B antigens
presents challenges for the production and regulation of inactivated quadrivalent
vaccines, including the potential for cross-reactivity of the reagents used in
identity and potency assays because of the relative close relatedness of the
hemagglutinin (HA) from the two virus lineages. Monoclonal antibodies (mAbs)
specific for the two lineages of influenza B HA were generated and characterized
and used to set-up simple identity tests that distinguish the influenza B
antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific
mAbs bound well to the HA of influenza B strains included in influenza vaccines
over a period of more than 10 years, suggesting that identity tests using such
lineage-specific mAbs would not necessarily have to be updated with every
influenza B vaccine strain change. These lineage-specific mAbs were also used in
an antibody capture ELISA format to quantify HA in vaccine samples, including
monovalent, trivalent, and quadrivalent vaccine samples from various
manufacturers. The results demonstrated correlation with HA values determined by
the traditional single radial immunodiffusion (SRID) assay. Further, the antibody
capture ELISA was able to distinguish heat-stressed vaccine from unstressed
vaccine, and was similar to the SRID in quantifying the resultant loss of
potency. These mAb reagents should be useful for further development of antibody
based alternative influenza B identity and potency assays.
PMID- 28423026
TI - The relationship between diabetes and colorectal cancer prognosis: A meta
analysis based on the cohort studies.
AB - INTRODUCTION: Though a meta-analysis reported the effect of diabetes on
colorectal prognosis in 2013, a series of large-scale long-term cohort studies
has comprehensively reported the outcome effect estimates on the relationship
between diabetes and colorectal prognosis, and their results were still
consistent. METHODS: We carried out an extensive search strategy in multiple
databases and conducted a meta-analysis on the effect of diabetes on colorectal
prognosis, based on the included 36 cohort studies, which contained 2,299,012
subjects. In order to collect more data, besides conventional methods, we used
the professional software to extract survival data from the Kaplan-Meier curves,
and analyzed both the 5-year survival rate and survival risk in overall survival,
cancer-specific survival, cardiovascular disease-specific survival, disease-free
survival, and recurrence-free survival, to comprehensively reflect the effect of
diabetes on colorectal prognosis. RESULTS: The results found that compared to
patients without diabetes, patients with diabetes will have a 5-year shorter
survival in colorectal, colon and rectal cancer, with a 18%, 19% and 16%
decreased in overall survival respectively. We also found similar results in
cancer-specific survival, cardiovascular disease-specific survival, disease-free
survival, and recurrence-free survival, but not all these results were
significant. We performed the subgroup analysis and sensitivity analysis to find
the source of heterogeneity. Their results were similar to the overall results.
CONCLUSIONS: Our meta-analysis suggested that diabetes had a negative effect on
colorectal cancer in overall survival. More studies are still needed to confirm
the relationship between diabetes and colorectal prognosis in cancer-specific
survival, cardiovascular disease-specific survival, disease-free survival, and
recurrence-free survival.
PMID- 28423027
TI - Comparison of T2*-weighted and QSM contrasts in Parkinson's disease to visualize
the STN with MRI.
AB - The subthalamic nucleus (STN) plays a crucial role in the surgical treatment of
Parkinson's disease (PD). Studies investigating optimal protocols for STN
visualization using state of the art magnetic resonance imaging (MRI) techniques
have shown that susceptibility weighted images, which display the magnetic
susceptibility distribution, yield better results than T1-weighted, T2-weighted,
and T2*-weighted contrasts. However, these findings are based on young healthy
individuals, and require validation in elderly individuals and persons suffering
from PD. Using 7T MRI, the present study set out to investigate which MRI
contrasts yielded the best results for STN visualization in 12 PD patients and
age-matched healthy controls (HC). We found that STNs were more difficult to
delineate in PD as reflected by a lower inter-rater agreement when compared to
HCs. No STN size differences were observed between the groups. Analyses of
quantitative susceptibility mapping (QSM) images showed a higher inter-rater
agreement reflected by increased Dice-coefficients. The location of the center of
mass of the STN was not affected by contrast. Overall, contrast-to-noise ratios
(CNR) were higher in QSM than in T2*-weighted images. This can at least
partially, explain the higher inter-rater agreement in QSM. The current results
indicate that the calculation of QSM contrasts contributes to an improved
visualization of the entire STN. We conclude that QSM contrast is the preferred
choice for the visualization of the STN in persons with PD as well as in aging
HC.
PMID- 28423028
TI - Four human Plasmodium species quantification using droplet digital PCR.
AB - Droplet digital polymerase chain reaction (ddPCR) is a partial PCR based on water
oil emulsion droplet technology. It is a highly sensitive method for detecting
and delineating minor alleles from complex backgrounds and provides absolute
quantification of DNA targets. The ddPCR technology has been applied for
detection of many pathogens. Here the sensitive assay utilizing ddPCR for
detection and quantification of Plasmodium species was investigated. The assay
was developed for two levels of detection, genus specific for all Plasmodium
species and for specific Plasmodium species detection. The ddPCR assay was
developed based on primers and probes specific to the Plasmodium genus 18S rRNA
gene. Using ddPCR for ultra-sensitive P. falciparum assessment, the lower level
of detection from concentrated DNA obtained from a high volume (1 mL) blood
sample was 11 parasites/mL. For species identification, in particular for samples
with mixed infections, a duplex reaction was developed for detection and
quantification P. falciparum/ P. vivax and P. malariae/ P. ovale. Amplification
of each Plasmodium species in the duplex reaction showed equal sensitivity to
singleplex single species detection. The duplex ddPCR assay had higher
sensitivity to identify minor species in 32 subpatent parasitaemia samples from
Cambodia, and performed better than real-time PCR. The ddPCR assay shows high
sensitivity to assess very low parasitaemia of all human Plasmodium species. This
provides a useful research tool for studying the role of the asymptomatic
parasite reservoir for transmission in regions aiming for malaria elimination.
PMID- 28423029
TI - Evaluating dispersal potential of an invasive fish by the use of aerobic scope
and osmoregulation capacity.
AB - Non-indigenous species (NIS) can impact marine biodiversity and ecosystem
structure and function. Once introduced into a new region, secondary dispersal is
limited by the physiology of the organism in relation to the ambient environment
and by complex interactions between a suite of ecological factors such as
presence of predators, competitors, and parasites. Early prediction of dispersal
potential and future 'area of impact' is challenging, but also a great asset in
taking appropriate management actions. Aerobic scope (AS) in fish has been linked
to various fitness-related parameters, and may be valuable in determining
dispersal potential of aquatic invasive species in novel environments. Round
goby, Neogobius melanostomus, one of the most wide-ranging invasive fish species
in Europe and North America, currently thrives in brackish and fresh water, but
its ability to survive in high salinity waters is unknown to date. We show that
AS in round goby is reduced by 30% and blood plasma osmolality increased
(indicating reduced capacity for osmoregulation) at salinities approaching
oceanic conditions, following slow ramping (5 PSU per week) and subsequent long
term acclimation to salinities ranging between 0 and 30 PSU (8 days at final
treatment salinities before blood plasma osmolality measurements, 12-20
additional days before respirometry). Survival was also reduced at the highest
salinities yet a significant proportion (61%) of the fish survived at 30 PSU.
Reduced physiological performance at the highest salinities may affect growth and
competitive ability under oceanic conditions, but to what extent reduced AS and
osmoregulatory capacity will slow the current 30 km year-1 rate of advance of the
species through the steep salinity gradient from the brackish Baltic Sea and into
the oceanic North Sea remains speculative. An unintended natural experiment is in
progress to test whether the rate of advance slows down. At the current rate of
advance the species will reach the oceanic North Sea by 2018/2019, therefore time
for taking preventative action is short.
PMID- 28423030
TI - Molecular characterization of Cryptosporidium and Giardia from the Tasmanian
devil (Sarcophilus harrisii).
AB - The Tasmanian devil (Sarcophilus harrisii) is a carnivorous marsupial found only
in the wild in Tasmania, Australia. Tasmanian devils are classified as endangered
and are currently threatened by devil facial tumour disease, a lethal
transmissible cancer that has decimated the wild population in Tasmania. To
prevent extinction of Tasmanian devils, conservation management was implemented
in 2003 under the Save the Tasmanian Devil Program. This study aimed to assess if
conservation management was altering the interactions between Tasmanian devils
and their parasites. Molecular tools were used to investigate the prevalence and
diversity of two protozoan parasites, Cryptosporidium and Giardia, in Tasmanian
devils. A comparison of parasite prevalence between wild and captive Tasmanian
devils showed that both Cryptosporidium and Giardia were significantly more
prevalent in wild devils (p < 0.05); Cryptosporidium was identified in 37.9% of
wild devils but only 10.7% of captive devils, while Giardia was identified in
24.1% of wild devils but only 0.82% of captive devils. Molecular analysis
identified the presence of novel genotypes of both Cryptosporidium and Giardia.
The novel Cryptosporidium genotype was 98.1% similar at the 18S rDNA to
Cryptosporidium varanii (syn. C. saurophilum) with additional samples identified
as C. fayeri, C. muris, and C. galli. Two novel Giardia genotypes, TD genotype 1
and TD genotype 2, were similar to G. duodenalis from dogs (94.4%) and a Giardia
assemblage A isolate from humans (86.9%). Giardia duodenalis BIV, a zoonotic
genotype of Giardia, was also identified in a single captive Tasmanian devil.
These findings suggest that conservation management may be altering host-parasite
interactions in the Tasmanian devil, and the presence of G. duodenalis BIV in a
captive devil points to possible human-devil parasite transmission.
PMID- 28423031
TI - Comorbidities of rheumatoid arthritis: Results from the Korean National Health
and Nutrition Examination Survey.
AB - This study aimed to evaluate the prevalence of comorbidities in patients with
rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012
Korea National Health and Nutrition Examination Survey (KNHANES), which assesses
the general health status of populations in South Korea using interviews and
basic health assessment, was analyzed retrospectively. Weighted prevalence and
odds ratio (OR) of comorbidities were analyzed in patients with RA compared with
the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was
1.5%. Patients with RA were older and more female predominant than subjects
without RA. The prevalence of living in an urban area, college graduation,
alcohol consumption and smoking was lower in patients with RA than non-RA.
Patients with RA had more comorbidities including hypertension, dyslipidemia,
myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon
cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and
chronic kidney disease. After adjusting socioeconomic and lifestyle
characteristics, RA was associated with an increased prevalence of MI or angina
(OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09,
p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR
1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and
hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA
population. Prevalence of solid cancer was not significantly associated with RA
after adjustment.
PMID- 28423032
TI - Complete study demonstrating the absence of rhabdovirus in a distinct Sf9 cell
line.
AB - A putative novel rhabdovirus (SfRV) was previously identified in a Spodoptera
frugiperda cell line (Sf9 cells [ATCC CRL-1711 lot 58078522]) by next generation
sequencing and extensive bioinformatic analysis. We performed an extensive
analysis of our Sf9 cell bank (ATCC CRL-1711 lot 5814 [Sf9L5814]) to determine
whether this virus was already present in cells obtained from ATCC in 1987.
Inverse PCR of DNA isolated from Sf9 L5814 cellular DNA revealed integration of
SfRV sequences in the cellular genome. RT-PCR of total RNA showed a deletion of
320 nucleotides in the SfRV RNA that includes the transcriptional motifs for
genes X and L. Concentrated cell culture supernatant was analyzed by sucrose
density gradient centrifugation and revealed a single band at a density of 1.14
g/ml. This fraction was further analysed by electron microscopy and showed
amorphous and particulate debris that did not resemble a rhabdovirus in
morphology or size. SDS-PAGE analysis confirmed that the protein composition did
not contain the typical five rhabdovirus structural proteins and LC-MS/MS
analysis revealed primarily of exosomal marker proteins, the SfRV N protein, and
truncated forms of SfRV N, P, and G proteins. The SfRV L gene fragment RNA
sequence was recovered from the supernatant after ultracentrifugation of the 1.14
g/ml fraction treated with diethyl ether suggesting that the SfRV L gene fragment
sequence is not associated with a diethyl ether resistant nucleocapsid.
Interestingly, the 1.14 g/ml fraction was able to transfer baculovirus DNA into
Sf9L5814 cells, consistent with the presence of functional exosomes. Our results
demonstrate the absence of viral particles in ATCC CRL-1711 lot 5814 Sf9 cells in
contrast to a previous study that suggested the presence of infectious
rhabdoviral particles in Sf9 cells from a different lot. This study highlights
how cell lines with different lineages may present different virosomes and
therefore no general conclusions can be drawn across Sf9 cells from different
laboratories.
PMID- 28423033
TI - Can soda ash dumping grounds provide replacement habitats for digger wasps
(Hymenoptera, Apoidea, Spheciformes)?
AB - BACKGROUND: Published sources document a loss of biodiversity at an extreme rate,
mainly because natural and semi-natural ecosystems are becoming fragmented and
isolated, thus losing their biological functions. These changes significantly
influence biological diversity, which is a complex phenomenon that changes over
time. Contemporary ecologists must therefore draw attention to anthropogenic
replacement habitats and increase their conservation status. In our studies we
show the positive role of soda ash dumping grounds as an alternative habitat for
digger wasps, especially the thermophilic species. METHODOLOGY/PRINCIPAL
FINDINGS: In the years 2007-2010 we carried out investigations in postindustrial
soda ash dumping grounds located in Central Poland. We demonstrated that these
areas serve as replacement habitats for thermophilic species of Spheciformes and,
indirectly, for their potential prey. The studies were conducted in three
microhabitat types, varying in soil moisture, salinity and alkalinity, that were
changing in the course of ecological succession. We trapped 2571 specimens
belonging to 64 species of digger wasps. Species typical of open sunny spaces
comprised 73% of the whole inventory. The obtained results suggest that the stage
of succession determines the richness, abundance and diversity of Spheciformes.
The most favorable conditions for digger wasps were observed in habitats at late
successional stages. CONCLUSIONS/SIGNIFICANCE: Our results clearly showed that
these habitats were replacement habitats for thermophilous Spheciformes,
including rare taxa that require genetic, species and ecosystem protection,
according to the Biodiversity Convention. We showed that some types of industry
might play a positive role in the preservation of taxa in the landscape, and that
even degraded industrial wasteland can replace habitats under anthropopressure,
serving as refugia of biological diversity, especially for disturbance-dependent
species.
PMID- 28423034
TI - Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within
tumour from perineural squamous cell carcinoma patients.
AB - Perineural spread of tumour cells along cranial nerves is a severe complication
of primary cutaneous squamous cell carcinomas of the head and neck region. While
surgical excision of the tumour is the treatment of choice, removal of all the
tumour is often complicated by the neural location and recurrence is frequent.
Non-invasive immune treatments such as checkpoint inhibitor blockade may be
useful in this set of tumours although little is understood about the immune
response to perineural spread of squamous cell carcinomas. Immunohistochemistry
studies suggest that perineural tumour contains a lymphocyte infiltrate but it is
difficult to quantitate the different proportions of immune cell subsets and
expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow
cytometry of excised perineural tumour tissue, we show that a T cell infiltrate
is prominent in addition to less frequent B cell, NK cell and NKT cell
infiltrates. CD8 T cells are more frequent than other T cells in the tumour
tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing
cells was significantly greater in the tumour relative to the blood, a pattern
that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using
immunohistochemistry, PD-1 and PD-L1-expression could be detected in close
proximity amongst perineural tumour tissue. The data suggest that perineural SCC
contains a mixture of immune cells with a predominant T cell infiltrate
containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+
and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local
antibody blockade of these checkpoint inhibitors.
PMID- 28423035
TI - Genetic profiling of putative breast cancer stem cells from malignant pleural
effusions.
AB - A common symptom during late stage breast cancer disease is pleural effusion,
which is related to poor prognosis. Malignant cells can be detected in pleural
effusions indicating metastatic spread from the primary tumor site. Pleural
effusions have been shown to be a useful source for studying metastasis and for
isolating cells with putative cancer stem cell (CSC) properties. For the present
study, pleural effusion aspirates from 17 metastatic breast cancer patients were
processed to propagate CSCs in vitro. Patient-derived aspirates were cultured
under sphere forming conditions and isolated primary cultures were further sorted
for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally,
sphere forming efficiency of CSC and non-CSC subpopulations was determined. In
order to genetically characterize the different tumor subpopulations, DNA was
isolated from pleural effusions before and after cell sorting, and compared with
corresponding DNA copy number profiles from primary tumors or bone metastasis
using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells
had a higher potential to form spheres when compared to CSC subpopulations. In
most cases, cell sorting did not yield sufficient cells for copy number analysis.
A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant
copy number profiles similar to the respective primary tumor. However, most
sorted subpopulations showed a balanced profile indicating an insufficient amount
of tumor cells and low sensitivity of the sequencing method. Finally, we were
able to establish a long term cell culture from one pleural effusion sample,
which was characterized in detail. In conclusion, we confirm that pleural
effusions are a suitable source for enrichment of putative CSC. However,
sequencing based molecular characterization is impeded due to insufficient
sensitivity along with a high number of normal contaminating cells, which are
masking genetic alterations of rare cancer (stem) cells.
PMID- 28423036
TI - Metabolic syndrome, serum uric acid and renal risk in patients with T2D.
AB - BACKGROUND AND AIMS: Metabolic Syndrome (Mets) and increased serum uric acid
(SUA), are well known renal risk predictors and often coexist in patients with
type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD
is at present unclear. METHODS AND RESULTS: Within the AMD Annals database we
identified patients with T2D and normal renal function and urine albumin
excretion at baseline and regular follow-up visits during a 4-year period. Blood
pressure, BMI, HDL, triglycerides, and SUA were available in 14,267 patients. The
association between Mets and/or hyperuricemia (HU, top fifth gender specific
quintile) and the occurrence of renal outcomes were evaluated. RESULTS: At
baseline 59% of patients (n = 8,408) showed Mets and 18% (n = 2,584) HU. Over the
4-year follow-up, 14% (n = 1,990) developed low eGFR (i.e. below 60 mL/min/1.73
m2), and 26% (n = 3,740) albuminuria. After adjustment for confounders,
BP>=130/85, low HDL, triglycerides >=150 and HU were independently related to the
development of low eGFR (1.57, P<0.001; 1.13, P = 0.056; 1.18, P = 0.008; 1.26, P
= 0.001) and of albuminuria (1.35, P<0.001; 1.18, P = 0.001; 1.15, P = 0.002;
1.24, P = 0.001), respectively. The incidence of low eGFR was higher in patients
with HU independent of the presence or absence of Mets (21%, OR 1.30, p = 0.009
and 20%, 1.57, p<0.000 respectively), while albuminuria occurred more frequently
in those with Mets and HU (32%, OR 1.25, p = 0.005) as compared to the reference
group. CONCLUSIONS: HU and Mets are independent predictors of CKD and its
individual components in patients with T2D.
PMID- 28423037
TI - Identification of candidate chemosensory genes by transcriptome analysis in
Loxostege sticticalis Linnaeus.
AB - Loxostege sticticalis Linnaeus is an economically important agricultural pest,
and the larvae cause great damage to crops, especially in Northern China.
However, effective and environmentally friendly chemical methods for controlling
this pest have not been discovered to date. In the present study, we performed
HiSeq2500 sequencing of transcriptomes of the male and female adult antennae,
adult legs and third instar larvae, and we identified 54 candidate odorant
receptors (ORs), including 1 odorant receptor coreceptor (Orco) and 5 pheromone
receptors (PRs), 18 ionotropic receptors (IRs), 13 gustatory receptors (GRs), 34
odorant binding proteins (OBPs), including 1 general odorant binding protein
(GOBP1) and 3 pheromone binding proteins (PBPs), 10 chemosensory proteins (CSPs)
and 2 sensory neuron membrane proteins (SNMPs). The results of RNA-Seq and RT
qPCR analyses showed the expression levels of most genes in the antennae were
higher than that in the legs and larvae. Furthermore, PR4, OR1-4, 7-11, 13-15,
23, 29-32, 34, 41, 43, 47/IR7d.2/GR5b, 45, 7/PBP2-3, GOBP1, OBP3, 8 showed female
antennae-biased expression, while PR1/OBP2, 7/IR75d/CSP2 showed male antennae
biased expression. However, IR1, 7d.3, 68a/OBP11, 20-22, 28/CSP9 had larvae
enriched expression, and OBP15, 17, 25, 29/CSP5 were mainly expressed in the
legs. The results shown above indicated that these genes might play a key role in
foraging, seeking mates and host recognition in the L. sticticalis. Our findings
will provide the basic knowledge for further studies on the molecular mechanisms
of the olfactory system of L. sticticalis and potential novel targets for pest
control strategies.
PMID- 28423038
TI - Attentional bias modification training for insomnia: A double-blind placebo
controlled randomized trial.
AB - BACKGROUND: Attentional bias toward sleep-related information is believed to play
a key role in insomnia. If attentional bias is indeed of importance, changing
this bias should then in turn have effects on insomnia complaints. In this double
blind placebo controlled randomized trial we investigated the efficacy of
attentional bias modification training in the treatment of insomnia. METHOD: We
administered baseline, post-test, and one-week follow-up measurements of insomnia
severity, sleep-related worry, depression, and anxiety. Participants meeting DSM
5 criteria for insomnia were randomized into an attentional bias training group
(n = 67) or a placebo training group (n = 70). Both groups received eight
training sessions over the course of two weeks. All participants kept a sleep
diary for four consecutive weeks (one week before until one week after the
training sessions). RESULTS: There was no additional benefit for the attentional
bias training over the placebo training on sleep-related indices/outcome
measures. CONCLUSIONS: The absence of the effect may be explained by the fact
that there was neither attentional bias at baseline nor any reduction in the bias
after the training. Either way, this study gives no support for attentional bias
modification training as a stand-alone intervention for ameliorating insomnia
complaints.
PMID- 28423039
TI - Electricity forecasting on the individual household level enhanced based on
activity patterns.
AB - Leveraging smart metering solutions to support energy efficiency on the
individual household level poses novel research challenges in monitoring usage
and providing accurate load forecasting. Forecasting electricity usage is an
especially important component that can provide intelligence to smart meters. In
this paper, we propose an enhanced approach for load forecasting at the household
level. The impacts of residents' daily activities and appliance usages on the
power consumption of the entire household are incorporated to improve the
accuracy of the forecasting model. The contributions of this paper are threefold:
(1) we addressed short-term electricity load forecasting for 24 hours ahead, not
on the aggregate but on the individual household level, which fits into the
Residential Power Load Forecasting (RPLF) methods; (2) for the forecasting, we
utilized a household specific dataset of behaviors that influence power
consumption, which was derived using segmentation and sequence mining algorithms;
and (3) an extensive load forecasting study using different forecasting
algorithms enhanced by the household activity patterns was undertaken.
PMID- 28423040
TI - Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type
10 (SCA10) expansions.
AB - Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia
disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the
ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion
contains a complex sequence of penta- and heptanucleotide interruption motifs
which is followed by a pure tract of tandem ATCCT repeats of unknown length at
its 3'-end. Intriguingly, expansions that carry these interruption motifs
correlate with an epileptic seizure phenotype and are unstable despite the theory
that interruptions are expected to stabilize expanded repeats. To examine the
apparent contradiction of unstable, interruption-positive SCA10 expansion alleles
and to determine whether the instability originates outside of the interrupted
region, we sequenced approximately 1 kb of the 5'-end of SCA10 expansions using
the ATCCT-PCR product in individuals across multiple generations from four SCA10
families. We found that the greatest instability within this region occurred in
paternal transmissions of the allele in stretches of pure ATTCT motifs while the
intervening interrupted sequences were stable. Overall, the ATCCT interruption
changes by only one to three repeat units and therefore cannot account for the
instability across the length of the disease allele. We conclude that the AT-rich
interruptions locally stabilize the SCA10 expansion at the 5'-end but do not
completely abolish instability across the entire span of the expansion. In
addition, analysis of the interruption alleles across these families support a
parsimonious single origin of the mutation with a shared distant ancestor.
PMID- 28423041
TI - Modeling the shape and composition of the human body using dual energy X-ray
absorptiometry images.
AB - There is growing evidence that body shape and regional body composition are
strong indicators of metabolic health. The purpose of this study was to develop
statistical models that accurately describe holistic body shape, thickness, and
leanness. We hypothesized that there are unique body shape features that are
predictive of mortality beyond standard clinical measures. We developed
algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans
into body thickness and leanness images. We performed statistical appearance
modeling (SAM) and principal component analysis (PCA) to efficiently encode the
variance of body shape, leanness, and thickness across sample of 400 older
Americans from the Health ABC study. The sample included 200 cases and 200
controls based on 6-year mortality status, matched on sex, race and BMI. The
final model contained 52 points outlining the torso, upper arms, thighs, and bony
landmarks. Correlation analyses were performed on the PCA parameters to identify
body shape features that vary across groups and with metabolic risk. Stepwise
logistic regression was performed to identify sex and race, and predict mortality
risk as a function of body shape parameters. These parameters are novel body
composition features that uniquely identify body phenotypes of different groups
and predict mortality risk. Three parameters from a SAM of body leanness and
thickness accurately identified sex (training AUC = 0.99) and six accurately
identified race (training AUC = 0.91) in the sample dataset. Three parameters
from a SAM of only body thickness predicted mortality (training AUC = 0.66,
validation AUC = 0.62). Further study is warranted to identify specific
shape/composition features that predict other health outcomes.
PMID- 28423042
TI - Transforming growth factor beta1 enhances heme oxygenase 1 expression in human
synovial fibroblasts by inhibiting microRNA 519b synthesis.
AB - BACKGROUND: Osteoarthritis (OA) is manifested by synovial inflammation and
cartilage destruction that is directly linked to synovitis, joint swelling and
pain. In the light of the role of synovium in the pathogenesis and the symptoms
of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms
and progression of OA. Transforming growth factor beta 1 (TGF-beta1), a secreted
homodimeric protein, possesses unique and potent anti-inflammatory and immune
regulatory properties in many cell types. Heme oxygenase 1 (HO-1) is an inducible
anti-inflammatory and stress responsive enzyme that has been proven to prevent
injuries caused by many diseases. Despite the similar anti-inflammatory profile
and their involvement in the pathogenesis of arthritic diseases, no studies have
as yet explored the possibility of any association between the expression of TGF
beta1 and HO-1. METHODOLOGY/PRINCIPAL FINDINGS: TGF-beta1-induced HO-1 expression
was examined by HO-1 promoter assay, qPCR, and Western blotting. The siRNAs and
enzyme inhibitors were utilized to determine the intermediate involved in the
signal transduction pathway. We showed that TGF-beta1 stimulated the synthesis of
HO-1 in a concentration- and time-dependent manner, which can be mitigated by
blockade of the phospholipase (PLC)gamma/protein kinase C alpha (PKC)alpha
pathway. We also showed that the expression of miRNA-519b, which blocks HO-1
transcription, is inhibited by TGF-beta1, and the suppression of miRNA 519b could
be reversed via blockade of the PLCgamma/PKCalpha pathway.
CONCLUSIONS/SIGNIFICANCE: TGF-beta1 stimulated the expression of HO-1 via
activating the PLCgamma/PKCalpha pathway and suppressing the downstream
expression of miRNA-519b. These results may shed light on the pathogenesis and
treatment of OA.
PMID- 28423043
TI - Essential neonatal care utilization and associated factors among mothers in
public health facilities of Aksum Town, North Ethiopia, 2016.
AB - BACKGROUND: Globally, neonatal death accounts about 44% of child death in 2013.
Ethiopia is one of the ten countries with the highest number of neonatal death.
Worldwide, more than 43% of deaths among under five year children is contributed
by neonates. Half of the neonatal death occur in the first day of life.
Recommendations about newborn care practices may conflict with local beliefs and
practices. So, it is important to understand the existing newborn care practice
and factors affecting it in order to take interventions so as to decrease
neonatal death. OBJECTIVE: To assess magnitude of essential neonatal care
utilization and associated factors among women visiting public health facilities
in Aksum Town, Tigray, Northern Ethiopia, 2015. METHODS: Facility based cross
sectional study was conducted from December 30, 2015 to January 31, 2016.The
sampled population are 423 women who gave live births within the last 6 months
prior to data collection. Systematic random sampling technique was employed. Data
were entered, coded and cleaned using Epi info version 7, and SPSS Version 21
software was used for analysis. Both bivariable and multivariable logistic
regression models were used to determine factors associated with essential
neonatal care utilization. Variables with P-value <0.2 in the bivariable logistic
regression model were included in to multivariable logistic regression model, and
finally variables with P-value <0.05 were considered as independent factors. Odds
ratio was used to measure strength of association at 95% confidence level.
RESULT: A total of 423 mothers included in the study. Prevalence of safe cord
care, optimal breast feeding, thermal care and baby received Tetracycline eye
ointment and vaccine at birth were 42.8%, 63.1%, 32.6% and 44.7% among the
respondents respectively. Only 113(26.7%) of the participants fulfilled essential
new born care practice. Occupation, parity and counseling on essential new born
care during delivery were significantly associated with utilization of essential
new born care. Employed women (AOR = 7.08; 95% CI (2.21, 12.72), 2-3 number of
deliveries (AOR = 1.84; 95% CI (1.04, 3.26) and received counseling about
essential new born car during delivery (AOR = 3.36; 95% CI (1.86, 6.08) were more
likely to practice essential neonatal care practice than their counterparts.
CONCLUSION AND RECOMMENDATION: Around three-fourth of mothers were not practicing
Essential Newborn Care (ENC). Occupation, parity and essential new born care
counseling during delivery were significantly associated with utilization of ENC.
Promotion of information at community level, women empowerment and staff training
is recommended.
PMID- 28423044
TI - The long term outcome of micturition, defecation and sexual function after spinal
surgery for cauda equina syndrome.
AB - BACKGROUND: Cauda equina syndrome (CES) is a rare neurologic complication of
lumbar herniated disc for which emergency surgical decompression should be
undertaken. Despite the common belief that the restoration of functions that are
affected by CES can take several years postoperatively, follow up seldom exceeds
the first year after surgery. Long term outcome of especially micturition,
defecation and sexual function-which are by definition affected in CES-are
unknown. The aim of this study is to evaluate 1) postoperative long term outcome
of micturition, defecation and sexual function in CES patients 2) attitude of
patients towards received hospital care with regard to (recovery of) these
functions. METHODS: CES patients were selected by screening the records of all
patients operated on lumbar herniated disc in our university hospital between
1995-2010. A questionnaire was sent to the selected CES patients evaluating
current complaints of micturition, defecation and sexual function and attitude
towards delivered care with focus on micturition, defecation and sexual function.
RESULTS: Thirty-seven of 66 eligible CES patients were included (response rate
71%, inclusion rate 56%). Median time after surgery was 13.8 years (range 5.8
21.8 years). Dysfunction at follow up was highly prevalent: 38% micturition
dysfunction, 43% defecation dysfunction and 54% sexual dysfunction. Younger age
at presentation was associated with sexual dysfunction at follow up: for every
year younger at presentation, odds ratio for sexual dysfunction at follow up was
1.11 (p = 0.035). Other associations with outcome were not identified. Two-third
of the CES patients wished their neurosurgeon had given them more prognostic
information about micturition, defecation and sexual function. CONCLUSION: The
presented data demonstrate that dysfunction of micturition, defecation and sexual
function are still highly prevalent in a large number of CES patients even years
postoperatively. These alarming follow up data probably have a devastating effect
on personal perceived quality of life, which should be studied in more detail.
CES patients communicate a clear demand for more prognostic information. The
presented figures enable clinicians to inform their CES patients more
realistically about long term postoperative outcome of micturition, defecation
and sexual function after surgical intervention.
PMID- 28423046
TI - Genetic structure and isolation by altitude in rice landraces of Yunnan, China
revealed by nucleotide and microsatellite marker polymorphisms.
AB - Rice landraces, a genetic reservoir for varietal improvement, are developed by
farmers through artificial selection during the long-term domestication process.
To efficiently conserve, manage, and use such germplasm resources, an
understanding of the genetic structure and differentiation of local rice
landraces is required. In this study, we analyzed 188 accessions of rice
landraces collected from localities across an altitudinal gradient from 425 to 2,
274 m above sea level in Yunnan Province, China using ten target genes and 48 SSR
markers. We detected clear differentiation of the rice landraces into indica and
japonica groups and further separation of the accessions in each group into two
subgroups according to altitude, including a lower altitude subgroup and higher
altitude subgroup. The AMOVA results showed significant genetic differentiation
among altitude zones at SSRs and most genes, except Os1977 and STS22. We further
determined that differentiation among landrace populations followed a model of
isolation by altitude, in which gene flow was higher among populations at similar
altitude levels than across different altitude levels. Our findings demonstrated
that both adaptation to altitude and altitude-dependent gene flow played key
roles in the genetic differentiation of rice landraces in Yunnan, China.
PMID- 28423045
TI - Characterization of antennal sensilla, larvae morphology and olfactory genes of
Melipona scutellaris stingless bee.
AB - There is growing evidence in the literature suggesting that caste differentiation
in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona,
is triggered by environmental signals, particularly a primer pheromone. With the
proper amount of food and a chemical stimulus, 25% of females emerge as queens,
in agreement with a long-standing "two loci/two alleles model" proposed in the
1950s. We surmised that these larvae must be equipped with an olfactory system
for reception of these chemical signals. Here we describe for the first time the
diversity of antennal sensilla in adults and the morphology of larvae of M.
scutellaris. Having found evidence for putative olfactory sensilla in larvae, we
next asked whether olfactory proteins were expressed in larvae. Since the
molecular basis of M. scutellaris is still unknown, we cloned olfactory genes
encoding chemosensory proteins (CSP) and odorant-binding proteins (OBPs) using M.
scutellaris cDNA template and primers designed on the basis CSPs and OBPs
previously reported from the European honeybee, Apis mellifera. We cloned two CSP
and two OBP genes and then attempted to express the proteins encoded by these
genes. With a recombinant OBP, MscuOBP8, and a combinatorial single-chain
variable fragment antibody library, we generated anti-MscuOBP8 monoclonal
antibody. By immunohistochemistry we demonstrated that the anti-MscuOBP8 binds
specifically to the MscuOBP8. Next, we found evidence that MscuOBP8 is expressed
in M. scutellaris larvae and it is located in the mandibular region, thus further
supporting the hypothesis of olfactory function in immature stages. Lastly,
molecular modeling suggests that MscuOBP8 may function as a carrier of primer
pheromones or other ligands.
PMID- 28423047
TI - Impact of body condition on influenza A virus infection dynamics in mallards
following a secondary exposure.
AB - Migratory waterfowl are often viewed as vehicles for the global spread of
influenza A viruses (IAVs), with mallards (Anas platyrhynchos) implicated as
particularly important reservoir hosts. The physical demands and energetic costs
of migration have been shown to influence birds' body condition; poorer body
condition may suppress immune function and affect the course of IAV infection.
Our study evaluated the impact of body condition on immune function and viral
shedding dynamics in mallards naturally exposed to an H9 IAV, and then
secondarily exposed to an H4N6 IAV. Mallards were divided into three treatment
groups of 10 birds per group, with each bird's body condition manipulated as a
function of body weight by restricting food availability to achieve either a
10%, -20%, or control body weight class. We found that mallards exhibit moderate
heterosubtypic immunity against an H4N6 IAV infection after an infection from an
H9 IAV, and that body condition did not have an impact on shedding dynamics in
response to a secondary exposure. Furthermore, body condition did not affect
aspects of the innate and adaptive immune system, including the acute phase
protein haptoglobin, heterophil/lymphocyte ratios, and antibody production.
Contrary to recently proposed hypotheses and some experimental evidence, our data
do not support relationships between body condition, infection and
immunocompetence following a second exposure to IAV in mallards. Consequently,
while annual migration may be a driver in the maintenance and spread of IAVs, the
energetic demands of migration may not affect susceptibility in mallards.
PMID- 28423048
TI - Correction: Impact of self-reported symptoms of allergic rhinitis and asthma on
sleep disordered breathing and sleep disturbances in the elderly with
polysomnography study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173075.].
PMID- 28423049
TI - InMAP: A model for air pollution interventions.
AB - Mechanistic air pollution modeling is essential in air quality management, yet
the extensive expertise and computational resources required to run most models
prevent their use in many situations where their results would be useful. Here,
we present InMAP (Intervention Model for Air Pollution), which offers an
alternative to comprehensive air quality models for estimating the air pollution
health impacts of emission reductions and other potential interventions. InMAP
estimates annual-average changes in primary and secondary fine particle (PM2.5)
concentrations-the air pollution outcome generally causing the largest monetized
health damages-attributable to annual changes in precursor emissions. InMAP
leverages pre-processed physical and chemical information from the output of a
state-of-the-science chemical transport model and a variable spatial resolution
computational grid to perform simulations that are several orders of magnitude
less computationally intensive than comprehensive model simulations. In
comparisons run here, InMAP recreates comprehensive model predictions of changes
in total PM2.5 concentrations with population-weighted mean fractional bias (MFB)
of -17% and population-weighted R2 = 0.90. Although InMAP is not specifically
designed to reproduce total observed concentrations, it is able to do so within
published air quality model performance criteria for total PM2.5. Potential uses
of InMAP include studying exposure, health, and environmental justice impacts of
potential shifts in emissions for annual-average PM2.5. InMAP can be trained to
run for any spatial and temporal domain given the availability of appropriate
simulation output from a comprehensive model. The InMAP model source code and
input data are freely available online under an open-source license.
PMID- 28423050
TI - Correction: Stiffness Effects in Rocker-Soled Shoes: Biomechanical Implications.
AB - [This corrects the article DOI: 10.1371/journal.pone.0169151.].
PMID- 28423051
TI - Biochemical and molecular characterization of the isocitrate dehydrogenase with
dual coenzyme specificity from the obligate methylotroph Methylobacillus
Flagellatus.
AB - The isocitrate dehydrogenase (MfIDH) with unique double coenzyme specificity from
Methylobacillus flagellatus was purified and characterized, and its gene was
cloned and overexpressed in E. coli as a fused protein. This enzyme is
homodimeric,-with a subunit molecular mass of 45 kDa and a specific activity of
182 U mg -1 with NAD+ and 63 U mg -1 with NADP+. The MfIDH activity was dependent
on divalent cations and Mn2+ enhanced the activity the most effectively. MfIDH
exhibited a cofactor-dependent pH-activity profile. The optimum pH values were
8.5 (NAD+) and 6.0 (NADP+).The Km values for NAD+ and NADP+ were 113 MUM and 184
MUM respectively, while the Km values for DL-isocitrate were 9.0 MUM (NAD+), 8.0
MUM (NADP+). The MfIDH specificity (kcat/Km) was only 5-times higher for NAD+
than for NADP+. The purified MfIDH displayed maximal activity at 60 degrees C.
Heat-inactivation studies showed that the MfIDH was remarkably thermostable,
retaining full activity at 50 degrees C and losting ca. 50% of its activity after
one hour of incubation at 75 degrees C. The enzyme was insensitive to the
presence of intermediate metabolites, with the exception of 2 mM ATP, which
caused 50% inhibition of NADP+-linked activity. The indispensability of the N6
amino group of NAD(P)+ in its binding to MfIDH was demonstrated. MfIDH showed
high sequence similarity with bacterial NAD(P)+-dependent type I isocitrate
dehydrogenases (IDHs) rather than with eukaryotic NAD+-dependent IDHs. The unique
double coenzyme specificity of MfIDH potentially resulted from the Lys340, Ile341
and Ala347 residues in the coenzyme-binding site of the enzyme. The discovery of
a type I IDH with double coenzyme specificity elucidates the evolution of this
subfamily IDHs and may provide fundamental information for engineering enzymes
with desired properties.
PMID- 28423052
TI - Inflammation-induced fetal growth restriction in rats is associated with
increased placental HIF-1alpha accumulation.
AB - INTRODUCTION: Hypoxia-inducible factor 1-alpha (HIF-1alpha) is the oxygen
sensitive subunit of the transcription factor HIF-1, and its expression is
increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal
growth restriction (FGR) and PE often share a common pathophysiology; however, it
is unknown whether increased placental HIF-1alpha occurs in FGR. We previously
demonstrated that aberrant maternal inflammation in rats resulted in altered
utero-placental perfusion and FGR, both of which were prevented by administration
of the nitric oxide mimetic glyceryl trinitrate (GTN). Our aim here was to
determine whether abnormal maternal inflammation causing FGR is linked to
placental HIF-1alpha accumulation and whether GTN administration could prevent
increases in placental HIF-1alpha. METHODS: Levels of inflammatory factors in
maternal plasma were measured using a multiplex assay after an injection of low
dose lipopolysaccharide (LPS) to rats on gestational day (GD) 13.5. Following
three additional daily LPS injections from GD14.5-16.5, GD17.5 placentas were
harvested for HIF-1alpha immunolocalisation; serial sections were also stained
for the hypoxia marker pimonidazole. A subset of rats received LPS injections
along with GTN delivered continuously (25 MUg/h via a transdermal patch) on
GD12.5-GD17.5. RESULTS: Within two hours of LPS administration, levels of
maternal pro-inflammatory cytokines were increased compared with saline-treated
controls. GD17.5 placentas of growth-restricted fetuses exhibited increased HIF
1alpha accumulation; however, this did not correlate with pimonidazole staining
for which no differences were observed between groups. Furthermore, the LPS
mediated increases in maternal inflammatory cytokine levels and placental HIF
1alpha accumulation did not occur in rats treated with GTN. DISCUSSION: Our
results demonstrate that inflammation-induced FGR is associated with increased
placental HIF-1alpha accumulation; however, expression of this transcription
factor may not correlate with regions of hypoxia in late-gestation placentas. The
GTN-mediated attenuation of placental HIF-1alpha accumulation in LPS-treated rats
provides insight into the mechanism by which GTN improves inflammation-induced
complications of pregnancy.
PMID- 28423053
TI - "She's a dog at the end of the day": Guide dog owners' perspectives on the
behaviour of their guide dog.
AB - A guide dog is a domestic dog (Canis familiaris) that is specifically educated to
provide mobility support to a blind or visually impaired owner. Current dog
suitability assessments focus on behavioural traits, including: trainability,
reactivity or attention to environmental stimuli, low aggressiveness, fearfulness
and stress behaviour, energy levels, and attachment behaviour. The aim of this
study was to find out which aspects of guide dog behaviour are of key importance
to guide dog owners themselves. Sixty-three semi-structured interview surveys
were carried out with guide dog owners. Topics included the behaviour of their
guide dog both within and outside their working role, and also focused on
examples of behaviour which might be considered outside a guide dog owner's
typical expectations. Both positive and negative examples and situations were
covered. This allowed for the discovery of new perspectives and emerging themes
on living and working with a guide dog. Thematic analysis of the results reveals
that a dog's safe behaviour in the face of traffic was the most important
positive aspect of a guide dog's behaviour and pulling or high tension on the
lead and /or harness was the most discussed negative aspect. Other aspects of
guide dog behaviour were highlighted as particularly pleasing or disappointing by
owners including attentiveness to the task, work, environment and owner;
confidence in work and decision making (with confident dogs resulting in
confident owners) obedience and control; calmness and locating objectives. The
results reveal important areas of behaviour that are not currently considered
priorities in guide dog assessments; these key areas were consistency of
behaviour, the dog's maturity and the dog's behaviour in relation to children.
The survey revealed a large range in what owners considered problematic or
pleasing behaviours and this highlights the heterogeneity in guide dog owners and
the potential multifarious roles of the guide dog. This study contributes to the
literature on which behaviour is considered appropriate or inappropriate in dogs
and on the nature of human-animal interactions.
PMID- 28423054
TI - Sleep duration and quality in relation to chronic kidney disease and glomerular
hyperfiltration in healthy men and women.
AB - BACKGROUND: It is unclear whether sleep duration and quality are associated with
chronic kidney disease (CKD) and glomerular hyperfiltration. The aim of this
study was to examine the association of sleep duration and quality with CKD and
glomerular hyperfiltration in young and middle-aged adults. METHODS: We conducted
a cross-sectional study of men and women who underwent a health checkup
examination, including assessment of sleep duration and quality (n = 241,607).
Chronic kidney disease (CKD) was defined as an estimated glomerular filtration
rate (eGFR) less than 60 ml/min/1.73 m2, and glomerular hyperfiltration was
defined as eGFR above the age-/sex-specific 95th percentile. RESULTS: In a
multinomial logistic regression analysis adjusting for relevant confounders, the
adjusted prevalence ratios for CKD (95% confidence interval) comparing sleep
durations of <= 5, 6, 8, and 9 hours with 7 hours were 1.22 (0.95-1.55), 0.93
(0.75-1.14), 0.97 (0.75-1.26), and 1.56 (1.06-2.30) in men and 0.98 (0.68-1.43),
1.03 (0.72-1.46), 1.39 (0.97-2.00), and 1.31 (0.78-2.22) in women, respectively.
The corresponding prevalence ratios (95% confidence interval) for glomerular
hyperfiltration were 1.00 (0.93-1.08), 0.97 (0.91-1.03), 1.03 (0.94-1.13), and
1.39 (1.13-1.72) in men and 1.04 (0.95-1.14), 0.96 (0.90-1.04), 1.11 (1.02-1.20),
and 1.28 (1.14-1.45) in women, respectively. Poor subjective sleep quality was
associated with glomerular hyperfiltration in men and women. CONCLUSION: In this
large study of young and middle-aged adults, we found that long sleep duration
was associated with CKD and glomerular hyperfiltration. Additionally, poor
subjective sleep quality was associated with increased prevalence of glomerular
hyperfiltration, suggesting the importance of adequate quantity and quality of
sleep for kidney function.
PMID- 28423055
TI - Comparative analysis of the expression level of recombinant ginsenoside
transforming beta-glucosidase in GRAS hosts and mass production of the
ginsenoside Rh2-Mix.
AB - The ginsenoside Rh2, a pharmaceutically active component of ginseng, is known to
have anticancer and antitumor effects. However, white ginseng and red ginseng
have extremely low concentrations of Rh2 or Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2,
and Rh3]. To enhance the production of food-grade ginsenoside Rh2, an edible
enzymatic bioconversion technique was developed adopting GRAS host strains. A
beta-glucosidase (BglPm), which has ginsenoside conversion ability, was expressed
in three GRAS host strains (Corynebacterium glutamicum, Saccharomyces cerevisiae
and Lactococus lactis) by using a different vector system. Enzyme activity in
these three GRAS hosts were 75.4%, 11.5%, and 9.3%, respectively, compared to
that in the E. coli pGEX 4T-1 expression system. The highly expressed BglPm_C in
C. glutamicum can effectively transform the ginsenoside Rg3-Mix [20(S)-Rg3, 20(R)
Rg3, Rk1, Rg5] to Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2, Rh3] using a scaled-up
biotransformation reaction, which was performed in a 10-L jar fermenter at pH
6.5/7.0 and 37 degrees C for 24 h. To our knowledge, this is the first report in
which 50 g of PPD-Mix (Rb1, Rb2, Rb3, Rc, and Rd) as a starting substrate was
converted to ginsenoside Rg3-Mix by acid heat treatment and then 24.5-g Rh2-Mix
was obtained by enzymatic transformation of Rg3-Mix through by BglPm_C.
Utilization of this enzymatic method adopting a GRAS host could be usefully
exploited in the preparation of ginsenoside Rh2-Mix in cosmetics, functional
food, and pharmaceutical industries, thereby replacing the E. coli expression
system.
PMID- 28423056
TI - Hair and stress: A pilot study of hair and cytokine balance alteration in healthy
young women under major exam stress.
AB - Mouse models show that experimental stress mimicking prolonged life-stress
exposure enhances neurogenic inflammation, induces adaptive immunity cytokine
imbalance characterized by a shift to Type 1 T-helper cell cytokines and
increases apoptosis of epithelial cells. This affects hair growth in otherwise
healthy animals. In this study, we investigate whether a prolonged naturalistic
life-stress exposure affects cytokine balance and hair parameters in healthy
humans. 33 (18 exam, 15 comparison) female medical students with comparable
sociobiological status were analyzed during a stressful final examination period,
at three points in time (T) 12 weeks apart. T1 was before start of the learning
period, T2 between the three-day written exam and an oral examination, and T3
after a 12 week rest and recovery from the stress of the examination period.
Assessments included: self-reported distress and coping strategies (Perceived
Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress
[TICS]), COPE), cytokines in supernatants of stimulated peripheral blood
mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis).
Comparison between students participating in the final medical exam at T2 and non
exam students, revealed significantly higher stress perception in exam students.
Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and
hair parameters changed significantly from T1 to T2 in the exam group, but not
the control. However, no group differences were found for cytokine balance or
hair parameters at T2. The study concludes that in humans, naturalistic stress,
as perceived during participation in a major medical exam, has the potential to
shift the immune response to TH1 and transiently hamper hair growth, but these
changes stay within a physiological range. Findings are instructive for patients
suffering from hair loss in times of high stress. Replication in larger and more
diverse sample populations is required, to assess suitability of trichogram
analysis as biological outcome for stress studies.
PMID- 28423058
TI - Accurate phenotyping: Reconciling approaches through Bayesian model averaging.
AB - Genetic research into complex diseases is frequently hindered by a lack of clear
biomarkers for phenotype ascertainment. Phenotypes for such diseases are often
identified on the basis of clinically defined criteria; however such criteria may
not be suitable for understanding the genetic composition of the diseases.
Various statistical approaches have been proposed for phenotype definition;
however our previous studies have shown that differences in phenotypes estimated
using different approaches have substantial impact on subsequent analyses.
Instead of obtaining results based upon a single model, we propose a new method,
using Bayesian model averaging to overcome problems associated with phenotype
definition. Although Bayesian model averaging has been used in other fields of
research, this is the first study that uses Bayesian model averaging to reconcile
phenotypes obtained using multiple models. We illustrate the new method by
applying it to simulated genetic and phenotypic data for Kofendred personality
disorder-an imaginary disease with several sub-types. Two separate statistical
methods were used to identify clusters of individuals with distinct phenotypes:
latent class analysis and grade of membership. Bayesian model averaging was then
used to combine the two clusterings for the purpose of subsequent linkage
analyses. We found that causative genetic loci for the disease produced higher
LOD scores using model averaging than under either individual model separately.
We attribute this improvement to consolidation of the cores of phenotype clusters
identified using each individual method.
PMID- 28423057
TI - Insertion of a ligand to HER2 in gB retargets HSV tropism and obviates the need
for activation of the other entry glycoproteins.
AB - Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL
and gB, activated in a cascade fashion by conformational modifications induced by
cognate receptors and intermolecular signaling. The receptors are nectin1 and
HVEM (Herpes virus entry mediator) for gD, and alphavbeta6 or alphavbeta8
integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to
the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in
gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells,
hence in highly specific non-attenuated oncolytic agents. Here, the scFv to HER2
was inserted in gB (gBHER2). The insertion re-targeted the virus tropism to the
HER2-positive cancer cells. This was unexpected since gB is known to be a
fusogenic glycoprotein, not a tropism determinant. The gB-retargeted recombinant
offered the possibility to investigate how HER2 mediated entry. In contrast to wt
gB, the activation of the chimeric gBHER2 did not require the activation of the
gD and of gH/gL by their respective receptors. Furthermore, a soluble form of
HER2 could replace the membrane-bound HER2 in mediating virus entry, hinting that
HER2 acted by inducing conformational changes to the chimeric gB. This study
shows that (i) gB can be modified and become the major determinant of HSV
tropism; (ii) the chimeric gBHER2 bypasses the requirement for receptor-mediated
activation of other essential entry glycoproteins.
PMID- 28423059
TI - High resolution microscopy reveals significant impacts of ocean acidification and
warming on larval shell development in Laternula elliptica.
AB - Environmental stressors impact marine larval growth rates, quality and sizes.
Larvae of the Antarctic bivalve, Laternula elliptica, were raised to the D-larvae
stage under temperature and pH conditions representing ambient and end of century
projections (-1.6 degrees C to +0.4 degrees C and pH 7.98 to 7.65). Previous
observations using light microscopy suggested pH had no influence on larval
abnormalities in this species. Detailed analysis of the shell using SEM showed
that reduced pH is in fact a major stressor during development for this species,
producing D-larvae with abnormal shapes, deformed shell edges and irregular
hinges, cracked shell surfaces and even uncalcified larvae. Additionally, reduced
pH increased pitting and cracking on shell surfaces. Thus, apparently normal
larvae may be compromised at the ultrastructural level and these larvae would be
in poor condition at settlement, reducing juvenile recruitment and overall
survival. Elevated temperatures increased prodissoconch II sizes. However, the
overall impacts on larval shell quality and integrity with concurrent ocean
acidification would likely overshadow any beneficial results from warmer
temperatures, limiting populations of this prevalent Antarctic species.
PMID- 28423060
TI - Phosphatidylcholine-specific phospholipase C inhibition down- regulates CXCR4
expression and interferes with proliferation, invasion and glycolysis in glioma
cells.
AB - BACKGROUND: The chemokine receptor CXCR4 plays a crucial role in tumors,
including glioblastoma multiforme (GBM), the most aggressive glioma.
Phosphatidylcholine-specific phospholipase C (PC-PLC), a catabolic enzyme of PC
metabolism, is involved in several aspects of cancer biology and its inhibition
down-modulates the expression of growth factor membrane receptors interfering
with their signaling pathways. In the present work we investigated the possible
interplay between CXCR4 and PC-PLC in GBM cells. METHODS: Confocal microscopy,
immunoprecipitation, western blot analyses, and the evaluation of migration and
invasion potential were performed on U87MG cells after PC-PLC inhibition with the
xanthate D609. The intracellular metabolome was investigated by magnetic
resonance spectroscopy; lactate levels and lactate dehydrogenase (LDH) activity
were analyzed by colorimetric assay. RESULTS: Our studies demonstrated that CXCR4
and PC-PLC co-localize and are associated on U87MG cell membrane. D609 reduced
CXCR4 expression, cell proliferation and invasion, interfering with AKT and EGFR
activation and expression. Metabolic analyses showed a decrease in intracellular
lactate concentration together with a decrement in LDH activity. CONCLUSIONS: Our
data suggest that inhibition of PC-PLC could represent a new molecular approach
in glioma biology not only for its ability in modulating cell metabolism, glioma
growth and motility, but also for its inhibitory effect on crucial molecules
involved in cancer progression.
PMID- 28423061
TI - Muscle contributions to medial tibiofemoral compartment contact loading following
ACL reconstruction using semitendinosus and gracilis tendon grafts.
AB - BACKGROUND: The muscle-tendon properties of the semitendinosus (ST) and gracilis
(GR) are substantially altered following tendon harvest for the purpose of
anterior cruciate ligament reconstruction (ACLR). This study adopted a
musculoskeletal modelling approach to determine how the changes to the ST and GR
muscle-tendon properties alter their contribution to medial compartment contact
loading within the tibiofemoral joint in post ACLR patients, and the extent to
which other muscles compensate under the same external loading conditions during
walking, running and sidestep cutting. MATERIALS AND METHODS: Motion capture and
electromyography (EMG) data from 16 lower extremity muscles were acquired during
walking, running and cutting in 25 participants that had undergone an ACLR using
a quadruple (ST+GR) hamstring auto-graft. An EMG-driven musculoskeletal model was
used to estimate the medial compartment contact loads during the stance phase of
each gait task. An adjusted model was then created by altering muscle-tendon
properties for the ST and GR to reflect their reported changes following ACLR.
Parameters for the other muscles in the model were calibrated to match the
experimental joint moments. RESULTS: The medial compartment contact loads for the
standard and adjusted models were similar. The combined contributions of ST and
GR to medial compartment contact load in the adjusted model were reduced by 26%,
17% and 17% during walking, running and cutting, respectively. These deficits
were balanced by increases in the contribution made by the semimembranosus muscle
of 33% and 22% during running and cutting, respectively. CONCLUSION: Alterations
to the ST and GR muscle-tendon properties in ACLR patients resulted in reduced
contribution to medial compartment contact loads during gait tasks, for which the
semimembranosus muscle can compensate.
PMID- 28423062
TI - Filamentous fungal carbon catabolite repression supports metabolic plasticity and
stress responses essential for disease progression.
AB - Aspergillus fumigatus is responsible for a disproportionate number of invasive
mycosis cases relative to other common filamentous fungi. While many fungal
factors critical for infection establishment are known, genes essential for
disease persistence and progression are ill defined. We propose that fungal
factors that promote navigation of the rapidly changing nutrient and structural
landscape characteristic of disease progression represent untapped clinically
relevant therapeutic targets. To this end, we find that A. fumigatus requires a
carbon catabolite repression (CCR) mediated genetic network to support in vivo
fungal fitness and disease progression. While CCR as mediated by the
transcriptional repressor CreA is not required for pulmonary infection
establishment, loss of CCR inhibits fungal metabolic plasticity and the ability
to thrive in the dynamic infection microenvironment. Our results suggest a model
whereby CCR in an environmental filamentous fungus is dispensable for initiation
of pulmonary infection but essential for infection maintenance and disease
progression. Conceptually, we argue these data provide a foundation for
additional studies on fungal factors required to support fungal fitness and
disease progression and term such genes and factors, DPFs (disease progression
factors).
PMID- 28423063
TI - Vitamin D status and its association with insulin resistance among type 2
diabetics: A case -control study in Ghana.
AB - BACKGROUND: Vitamin D plays a major role in physiological processes that modulate
mineral metabolism and immune function with probable link to several chronic and
infectious conditions. Emerging data suggests a possible influence of vitamin D
on glucose homeostasis. This study sought to provide preliminary information on
vitamin D status among Ghanaian type 2 diabetics and assessed its association
with glucose homeostasis. METHODS: In a case control study, 118 clinically
diagnosed Type 2 Diabetes Mellitus (T2DM) patients attending Diabetic Clinic at
the Nkawie Government Hospital were enrolled between October and December 2015.
Hundred healthy non-diabetics living in Nkawie district were selected as
controls. Structured questionnaires were administered to obtain socio-demographic
data. Venous blood samples were taken from both cases and controls to estimate
their FBG, Lipid profile spectrophotometrically and IPTH, 25OHD by ELISA.
Statistical analyses were performed using SPSS v20.0 Statistics. RESULTS: The
average age of the study participants was 58.81years for cases and 57.79year for
controls. There was vitamin D deficiency of 92.4% among T2DM cases and 60.2%
among the non diabetic controls. Vitamin D deficiency did not significantly
associate with HOMA-beta [T2DM: r2 = 0.0209, p = 0.1338 and Control: r2 = 0.0213,
p = 0.2703] and HOMA-IR [T2DM: r2 = 0.0233, p = 0.1132 and Control: r2 = 0.0214,
p = 0.2690] in both the controls and the cases. CONCLUSION: Vitamin D deficiency
is prevalent in both T2DM and non-diabetics. There is no association between
vitamin D deficiency and insulin resistance or beta cell function in our study
population. Vitamin D supplementation among type 2 diabetics is recommended.
PMID- 28423066
TI - Influence of maternal anxiety on child anxiety during dental care: cross
sectional study.
AB - CONTEXT AND OBJECTIVES:: Anxiety is usually classified as a disorder of neurotic
nature and is often related to contexts of stress, which may include worries,
motor tension and autonomic hyperactivity. The aim of this study was to assess
the influence of mothers' anxiety on their children's anxiety during dental care.
DESIGN AND SETTING:: Analytical cross-sectional study conducted at in a private
dentistry school in the south of Brazil. METHODS:: Convenience sampling was used.
All mothers of children undergoing treatment were invited to participate in this
study. Data to investigate anxiety related to dental treatment among the children
were collected through applying the Venham Picture Test (VPT) scale. For the
mothers, the Corah scale was applied. A self-administered sociodemographic
questionnaire with questions about demographic, behavioral, oral health and
dental service variables was also used. RESULTS:: 40 mother-child pairs were
included in the study. The results showed that 40% of the children were anxious
and 60% of the mothers were slightly anxious. Local anesthesia was the procedure
that caused most anxiety among the mothers, making them somewhat uncomfortable
and anxious (60%). Family income higher than R$ 1,577.00 had an influence on
maternal anxiety (75.6%). Maternal anxiety had an influence on child anxiety
(81.3%). CONCLUSION:: Most of the children showed the presence of anxiety, which
ranged from fear of dental care to panic, inferring that maternal anxiety has an
influence on children's anxiety. Dental procedures did not interfere with the
mothers' anxiety, but caused positive feelings, whereas they affected the
children more.
PMID- 28423064
TI - Biochemical evaluation of the anticancer potential of the polyamine-based
nanocarrier Nano11047.
AB - Synthesizing polycationic polymers directly from existing drugs overcomes the
drug-loading limitations often associated with pharmacologically inert
nanocarriers. We recently described nanocarriers formed from a first-generation
polyamine analogue, bis(ethyl)norspermine (BENSpm), that could simultaneously
target polyamine metabolism while delivering therapeutic nucleic acids. In the
current study, we describe the synthesis and evaluation of self-immolative
nanocarriers derived from the second-generation polyamine analogue PG-11047.
Polyamines are absolutely essential for proliferation and their metabolism is
frequently dysregulated in cancer. Through its effects on polyamine metabolism,
PG-11047 effectively inhibits tumor growth in cancer cell lines of multiple
origins as well as in human tumor mouse xenografts. Promising clinical trials
have been completed verifying the safety and tolerance of this rotationally
restricted polyamine analogue. We therefore used PG-11047 as the basis for
Nano11047, a biodegradable, prodrug nanocarrier capable of targeting polyamine
metabolism. Following exposure of lung cancer cell lines to Nano11047, uptake and
intracellular degradation into the parent compound PG-11047 was observed. The
release of PG-11047 highly induced the polyamine catabolic enzyme activities of
spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). By
contrast, the activity of ornithine decarboxylase (ODC), a rate-limiting enzyme
in polyamine biosynthesis and a putative oncogene, was decreased. Consequently,
intracellular levels of the natural polyamines were depleted concurrent with
tumor cell growth inhibition. This availability of Nano11047 as a novel drug form
and potential nucleic acid delivery vector will potentially benefit and encourage
future clinical studies.
PMID- 28423065
TI - Association of body mass index with clinical outcomes for in-hospital cardiac
arrest adult patients following extracorporeal cardiopulmonary resuscitation.
AB - BACKGROUND: Obesity might be associated with disturbance of cannulation in
situation of extracorporeal cardiopulmonary resuscitation (ECPR). However,
limited data are available on obesity in the setting of ECPR. Therefore, we
investigated the association between body mass index (BMI) and clinical outcome
in patients underwent ECPR. METHODS: From January 2004 to December 2013, in
hospital cardiac arrest patients who had ECPR were enrolled from a single-center
registry. We divided patients into four group according to BMI defined with the
WHO classification (underweight, BMI < 18.5, n = 14; normal weight, BMI = 18.5
24.9, n = 118; overweight, BMI = 25.0-29.9, n = 53; obese, BMI >= 30, n = 15).
The primary outcome was survival to hospital discharge. RESULTS: Analysis was
carried out for a total of 200 adult patients (39.5% females). Their median BMI
was 23.20 (interquartile range, 20.93-25.80). The rate of survival to hospital
discharge was 31.0%. There was no significant difference in survival to hospital
discharge among the four groups (underweight, 35.7%; normal, 31.4%; overweight,
30.2%; obese, 26.7%, p = 0.958). Neurologic outcomes (p = 0.85) and procedural
complications (p = 0.40) were not significantly different among the four groups
either. SOFA score, initial arrest rhythm, and CPR to extracorporeal membrane
oxygenation (ECMO) pump on time were significant predictors for survival to
discharge, but not BMI. CONCLUSION: BMI was not associated with in-hospital
mortality who underwent ECPR. Neurologic outcomes at discharge or procedural
complications following ECPR were not related with BMI either.
PMID- 28423067
TI - Isospora albicollis (Apicomplexa: Eimeriidae) in thrushes Turdus spp.
(Passeriformes: Turdidae), in southeastern Brazil.
AB - The aim of the present study was to report and describe Isospora albicollis
Lainson and Shaw, 1989 parasitizing a white-necked thrush Turdus albicollis
Vieillot, 1818 and a pale-breasted thrush Turdus leucomelas Vieillot, 1818 in two
different localities: the Itatiaia National Park and Cacaria, in southeastern
Brazil. The oocysts identified were ovoidal, 24.4 * 19.7 MUm, with a smooth,
bilayered wall, around 1.4 MUm thick. Oocyst residuum was absent, but a micropyle
and a polar granule were present. The sporocysts were ellipsoidal, 15.4 * 10.1
MUm. The Stieda body was knob-like to rounded and the sub-Stieda body was
prominent and wide. Sporocyst residuum was present, usually as a cluster of
granules that appear to be membrane-bounded. The sporozoites were vermiform with
one posterior refractile body and a centrally located nucleus. Besides recording
the new host T. leucomelas, the identification of I. albicollis in the Itatiaia
National Park and Cacaria, in southeastern Brazil, provide records of new
localities for its parasitism, and reveals the wide distribution and dispersion
of this coccidium in Brazil.
PMID- 28423068
TI - Suicide and meteorological factors in Sao Paulo, Brazil, 1996-2011: a time series
analysis.
AB - Objective:: Considering the scarcity of reports from intertropical latitudes and
the Southern Hemisphere, we aimed to examine the association between
meteorological factors and suicide in Sao Paulo. Method:: Weekly suicide records
stratified by sex were gathered. Weekly averages for minimum, mean, and maximum
temperature ( degrees C), insolation (hours), irradiation (MJ/m2), relative
humidity (%), atmospheric pressure (mmHg), and rainfall (mm) were computed. The
time structures of explanatory variables were modeled by polynomial distributed
lag applied to the generalized additive model. The model controlled for long-term
trends and selected meteorological factors. Results:: The total number of
suicides was 6,600 (5,073 for men), an average of 6.7 suicides per week (8.7 for
men and 2.0 for women). For overall suicides and among men, effects were
predominantly acute and statistically significant only at lag 0. Weekly average
minimum temperature had the greatest effect on suicide; there was a 2.28%
increase (95%CI 0.90-3.69) in total suicides and a 2.37% increase (95%CI 0.82
3.96) among male suicides with each 1 degrees C increase. Conclusion:: This
study suggests that an increase in weekly average minimum temperature has a short
term effect on suicide in Sao Paulo.
PMID- 28423069
TI - Trypophobia: an investigation of clinical features.
AB - OBJECTIVE: Trypophobia refers to the fear of, or aversion to, clusters of holes.
We assessed clinical features of trypophobia and investigated whether it most
resembled a specific phobia or obsessive-compulsive disorder. METHODS: An online
survey was conducted to gather information on sociodemographic variables, course
and duration, severity, associated features, comorbid psychiatric diagnoses, and
levels of psychological distress and impairment in individuals with trypophobia.
The survey also explored whether such individuals experienced more fear or
disgust, and whether symptoms showed more resemblance to a specific phobia or to
obsessive-compulsive disorder. Associations of symptom severity and duration with
degree of impairment were investigated. RESULTS: One hundred and ninety-five
individuals completed the questionnaire. Symptoms were chronic and persistent.
The most common associated comorbidities were major depressive disorder and
generalized anxiety disorder. Trypophobia was associated with significant
psychological distress and impairment. The majority of individuals experienced
disgust rather than fear when confronted with clusters of holes, but were more
likely to meet DSM-5 criteria for specific phobia than for obsessive-compulsive
disorder. Symptom severity and duration were associated with functional
impairment. CONCLUSIONS: Given that individuals with trypophobia suffer
clinically significant morbidity and comorbidity, this condition deserves further
attention from clinicians and researchers.
PMID- 28423070
TI - The Extended Log-Logistic Distribution: Properties and Application.
AB - We propose a new four-parameter lifetime model, called the extended log-logistic
distribution, to generalize the two-parameter log-logistic model. The new model
is quite flexible to analyze positive data. We provide some mathematical
properties including explicit expressions for the ordinary and incomplete
moments, probability weighted moments, mean deviations, quantile function and
entropy measure. The estimation of the model parameters is performed by maximum
likelihood using the BFGS algorithm. The flexibility of the new model is
illustrated by means of an application to a real data set. We hope that the new
distribution will serve as an alternative model to other useful distributions for
modeling positive real data in many areas.
PMID- 28423072
TI - Editors of Brazilian journals - a hard life that is getting harder!
PMID- 28423071
TI - On topological groups with an approximate fixed point property.
AB - A topological group G has the Approximate Fixed Point (AFP) property on a bounded
convex subset C of a locally convex space if every continuous affine action of G
on C admits a net ( x i ) , x i ? C , such that x i - g ? x i ? 0 for all g ? G .
In this work, we study the relationship between this property and amenability.
PMID- 28423073
TI - Purification of inulinases by changing the ionic strength of the medium and
precipitation with alcohols.
AB - The present study evaluated the purification of inulinase by changing the ionic
strength of the medium by addition of NaCl and CaCl2 followed by precipitation
with n-propyl alcohol or iso-propyl alcohol. The effects of the concentration of
alcohols and the rate of addition of alcohols in the crude extract on the
purification yield and purification factor were evaluated. Precipitation caused
an activation of enzyme and allowed purification factors up to 2.4-fold for both
alcohols. The purification factor was affected positively by the modification of
the ionic strength of the medium to 0.5 mol.L-1 NaCl before precipitation with
the alcohol (n-propyl or iso-propyl). A purification factor of 4.8-fold and an
enzyme yield of 78.1 % could be achieved by the addition of 0.5 mol.L-1 of NaCl
to the crude extract, followed by the precipitation with 50 % (v/v) of n-propyl
alcohol, added at a flow rate of 19.9 mL/min.
PMID- 28423074
TI - 7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C
chemical shift assignments.
AB - A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a
and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The
structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and
spectral comparison with related compounds, leading to complete assignment of the
1H and 13C NMR spectra.
PMID- 28423075
TI - Glass Microbeads in Analog Models of Thrust Wedges.
AB - Glass microbeads are frequently used in analog physical modeling to simulate weak
detachment zones but have been neglected in models of thrust wedges. Microbeads
differ from quartz sand in grain shape and in low angle of internal friction. In
this study, we compared the structural characteristics of microbeads and sand
wedges. To obtain a better picture of their mechanical behavior, we determined
the physical and frictional properties of microbeads using polarizing and
scanning electron microscopy and ring-shear tests, respectively. We built
shortening experiments with different basal frictions and measured the thickness,
slope and length of the wedges and also the fault spacings. All the microbeads
experiments revealed wedge geometries that were consistent with previous studies
that have been performed with sand. However, the deformation features in the
microbeads shortened over low to intermediate basal frictions were slightly
different. Microbeads produced different fault geometries than sand as well as a
different grain flow. In addition, they produced slip on minor faults, which was
associated with distributed deformation and gave the microbeads wedges the
appearance of disharmonic folds. We concluded that the glass microbeads may be
used to simulate relatively competent rocks, like carbonates, which may be
characterized by small-scale deformation features.
PMID- 28423076
TI - Transmissivity of Aquifer by Capture Zone Method: An Application in the Sete
Lagoas Karst Aquifer, MG, Brazil.
AB - Transmissivity is an important hydraulic parameter to determine the amount of
water passed horizontally across a given saturated thickness of an aquifer. The
techniques to quantify this parameter, such as grain size analyses or pumping
tests, can have limitations of time/spatial scale, viability, or economically.
One technique that can be used, but little adopted, is the capture zone analysis.
In this paper, capture zone analytical equations were used to estimate
transmissivity values in order to verify the effectiveness of this methodology as
alternative in situations where other traditional methods present implementation
difficulties. The results were compared with field data estimated by aquifer
tests conducted in the same region. A sensitivity analysis was also performed to
identify possible discrepancies between the analytical and field data results.
The aquifer studied was the Sete Lagoas Karst Aquifer in the urban region of the
municipality of Sete Lagoas, Brazil. The method proved to be a viable and
economical tool, where the analytical values compared to the aquifer tests showed
similarities, being confirmed by a sensitivity analysis. However, a reliable
potentiometric surface map, which enables the identification of the parameters
for analytical capture zone equations, is needed.
PMID- 28423077
TI - Early Devonian (Late Emsian) shark fin remains (Chondrichthyes) from the Parana
Basin, southern Brazil.
AB - We report on the pioneering discovery of Devonian fish remains in the Parana
Basin, which represents the southernmost record of fishes from that period in
mainland South America. The material comes from an outcrop at the lower portion
of the Sao Domingos Formation, within Sequence C of the Parana-Apucarana sub
basin in Tibagi, State of Parana. Marine invertebrates are abundant in the same
strata. The dark colored fish remains were collected in situ and represent
natural moulds of partially articulated shark fin rays (radials). No elements
such as teeth or prismatic cartilage have been preserved with the fins rays. This
can be attributed to the dissolution of calcium-phosphatic minerals at the early
stages of fossilization due to diagenetic processes possibly linked to strong
negative taphonomic bias. This may have contributed to the fact that fishes
remained elusive in the Devonian strata of this basin, despite substantial
geological work done in the Parana State in recent decades. In addition, the
scarcity of fish fossils may be explained by the fact that the Devonian rock
deposits in this basin originated in a vertebrate impoverished, cold marine
environment of the Malvinokaffric Realm, as previously suspected.
PMID- 28423078
TI - Characterization and bioactivities of a novel polysaccharide obtained from
Gracilariopsis lemaneiformis.
AB - Gracilariopsis lemaneiformis is a type of red alga that contains seaweed
polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide
fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis
lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural
analysis showed that GCP shows triple helical chain conformation when dissolved
in water and has many branches and long side chains. Also, 1->3 linkage is the
major linkage and the sugar structures are galactopyranose configurations linked
by beta-type glycosidic linkages. Two macromolecular substance fractions (GCP-1
and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography.
Moreover, a splenocyte damage assay and splenocyte proliferation assay were used
to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that
polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest
protection rate, that is, 92.8%, which significantly enhanced the splenocyte
proliferation, and GCP showed the highest proliferation rate, 9.30%. The results
suggested that this type of novel non-agar polysaccharide displayed remarkable
antioxidant and immunomodulatory activities and early alkali treatment could
decrease the activities. It may represent a potential material for health food
and clinical medicines.
PMID- 28423079
TI - The partitioning of food resources between two rodents in the subtropical region
of southern Brazil.
AB - The capybara (Hydrochoerus hydrochaeris) and nutria (Myocastor coypus) are
herbivorous semi-aquatic rodents. Although these rodents occur in sympatry in
southern South America, little is known about how the two species interact in
relationship to food resources. In this context, the aim of this study was to
analyze the food resource overlap, the feeding strategy and the diversity of the
diet of capybaras and nutria. A micro-histological analysis of feces was used to
study the diets. A total of 48 plant species belonging to 10 families were
identified in the diet of H. hydrochaeris, and a total of 49 species belonging to
14 families were identified in the diet of M. coypus. According to the Amundsen
graphical method, both rodents adopted a specialized strategy for feeding on
Poaceae and a generalized strategy for other families. The results of a
multivariate analysis of the dietary data showed significant differences between
the two rodent species and among the seasons. These differences between diets may
be related to the different proportions of each food item eaten. However, the
dietary overlap between the two rodents in the Taim wetland was high, suggesting
that partitioning of other resources ensured the coexistence of the species.
PMID- 28423080
TI - S-(+)- and R-(-)-linalool: a comparison of the in vitro anti-Aeromonas hydrophila
activity and anesthetic properties in fish.
AB - Linalool is the main compound of many essential oils and occurs in two isomeric
forms: S-(+)- and R-(-)-linalool. This study aimed to determine if linalool
isomers have different antimicrobial and anesthetic properties in fish. For this
purpose, these compounds were previously isolated from Lippia alba (Mill.)N. E.
Brown and Ocimum americanum L. essential oils. Antimicrobial effects were
evaluated through the microdilution test against Aeromonas hydrophila, an
important fish disease etiologic agent. Induction time until sedation, anesthesia
and recovery time were determined in silver catfish (Rhamdia quelen) through bath
exposure (60, 180, 300 or 500 MUL L-1). The results showed different biological
properties for the isomers being S-(+)-linalool the only active against A.
hydrophila at 3.2 mg mL-1. The sedation was induced without differences between
the compounds, however R-(-)-linalool promoted faster anesthesia. There were no
differences regarding the recovery time of the animals exposed to the linalool
isomers. Although both S-(+)- and R-(-)-linalool can be used for sedative
purposes, their use in A. hydrophila infection is inadvisable due to the high
effective concentration. Considering anesthesia as the main objective, the R-(-)
linalool demonstrated clear advantages at lower concentration.
PMID- 28423081
TI - Long-wavelength sensitive opsin (LWS) gene variability in Neotropical cichlids
(Teleostei: Cichlidae).
AB - Cichlid fishes are an important group in evolutionary biology due to their fast
speciation. This group depends widely of vision for feeding and reproduction.
During the evolutionary process it plays a significant role in interspecific and
intraspecific recognition and in its ecology. The molecular basis of vision is
formed by the interaction of the protein opsin and retinal chromophore. Long
wavelength sensitive opsin (LWS) gene is the most variable among the opsin genes
and it has an ecological significance. Current assay identifies interspecific
variation of Neotropical cichlids that would modify the spectral properties of
the LWS opsin protein and codons selected. Neotropical species present more
variable sites for LWS gene than those of the African lakes species. The LWS
opsin gene in Crenicichla britskii has a higher amino acid similarity when
compared to that in the African species, but the variable regions do not overlap.
Neotropical cichlids accumulate larger amounts of variable sites for LWS opsin
gene, probably because they are spread over a wider area and submitted to a wider
range of selective pressures by inhabiting mainly lotic environments.
Furthermore, the codons under selection are different when compared to those of
the African cichlids.
PMID- 28423082
TI - Comparative analysis of two different models of swimming applied to pregnant rats
born small for pregnant age.
AB - The aim of this study was to compare two models of swimming applied to pregnant
rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult
female rats to develop an inadequate intrauterine environment, leading to birth
of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to
different swimming programs. The exercise program 1 (Ex1) consisted of swimming
for 15 minutes, followed by 15 minutes of rest and another 15 minutes of
swimming, 3 days a week before and during pregnancy. Another program (Ex2) was
applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The
pregnant rats presented no interference on body weight and glycemia. The rats
submitted to Ex2 model showed decreased insulin and blood glucose levels by oral
glucose tolerance test, and reduction in area under curve values. The offspring
from dams submitted to both exercise protocols presented an increased rate of
newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher
of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of
60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth
restricted females. However, this protocol employed at pregnancy leads to
intrauterine growth restriction.
PMID- 28423083
TI - Autophagy protects against neural cell death induced by piperidine alkaloids
present in Prosopis juliflora (Mesquite).
AB - Prosopis juliflora is a shrub that has been used to feed animals and humans.
However, a synergistic action of piperidine alkaloids has been suggested to be
responsible for neurotoxic damage observed in animals. We investigated the
involvement of programmed cell death (PCD) and autophagy on the mechanism of cell
death induced by a total extract (TAE) of alkaloids and fraction (F32) from P.
juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial
cell co-culture. We saw that TAE (30 ug/mL) and F32 (7.5 ug/mL) induced reduction
in ATP levels and changes in mitochondrial membrane potential at 12 h exposure.
Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and
neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized
by decreases of P62 protein level, increase of LC3II expression and increase in
number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of
autophagy by bafilomycin and vinblastine increased the cell death induced by TAE
and autophagy induced by serum deprivation and rapamycin reduced cell death
induced by F32 at 24 h. These results indicate that the mechanism neural cell
death induced by these alkaloids involves PCD via caspase-9 activation and
autophagy, which seems to be an important protective mechanism.
PMID- 28423084
TI - Immune System Dysfunction in the Elderly.
AB - Human aging is characterized by both physical and physiological frailty that
profoundly affects the immune system. In this context aging is associated with
declines in adaptive and innate immunity established as immunosenescence.
Immunosenescence is a new concept that reflects the age-associated restructuring
changes of innate and adaptive immune functions. Thus elderly individuals usually
present chronic low-level inflammation, higher infection rates and chronic
diseases. A study of alterations in the immune system during aging could provide
a potentially useful biomarker for the evaluation of immune senescence treatment.
The immune system is the result of the interplay between innate and adaptive
immunity, yet the impact of aging on this function is unclear. In this article
the function of the immune system during aging is explored.
PMID- 28423085
TI - Molecular survey of Anaplasma platys and Ehrlichia canis in dogs from Campo
Grande, Mato Grosso do Sul, Brazil.
AB - This study investigated the frequency of infection by Anaplasma platys and
Ehrlichia canis in dogs submitted to animal health centers in Campo Grande, state
of Mato Grosso do Sul, Brazil. E. canis and A. platys showed infection
frequencies of 55.75% and 16.96%, respectively. The identity of the two species
was confirmed by DNA sequencing.
PMID- 28423086
TI - Evaluation of cytogenotoxicity, antioxidant and hypoglycemiant activities of
isolate compounds from Mansoa hirsuta D.C. (Bignoniaceae).
AB - Mansoa hirsuta (Bignoniaceae) is a native plant from caatinga in Brazilian
semiarid. This plant has been locally used as antimicrobial and hypoglycemiant
agents, but their action mechanisms and toxicity remain largely unknown.
Therefore, we evaluated the composition and antioxidant, cytoprotective and
hypoglycemiant effects of raw extract, fractions and compounds from leaves of M.
hirsuta. The cytogenotoxic effects of ursolic and oleanolic acids, the main
phytotherapic components of this plant, were assessed. The raw extract and
fractions presented steroids, saponins, flavonols, flavanonols, flavanones,
xanthones, phenols, tannins, anthocyanins, anthocyanidins and flavonoids. The
ethyl acetate fraction inhibited efficiently the cascade of lipid peroxidation
while the hydroalcoholic fraction was richer in total phenols and more efficient
in capturing 2,2-diphenyl-1-picrylhydrazyl (.DPPH) and 2,2'-azino-bis (3
ethylbenzthiazoline-6-sulfonic acid) (ABTS.+) radicals. The isolated fraction of
M. hirsuta also inhibited the alpha-amylase activity. Cytotoxic effects were
absent in both raw extract and fractions while ursolic+oleanolic acids were
efficient in protecting cells after exposure to hydrogen peroxide. Moreover, this
mixture of acid shad no significant interference on the mitotic index and
frequency of nuclear and/or chromosomal abnormalities in Allium cepa test.
Therefore, M. hirsuta represents a potential source of phytochemicals against
inflammatory and oxidative pathologies, including diabetes.
PMID- 28423087
TI - Epidemiological aspects of American cutaneous leishmaniasis (ACL) in an endemic
area of forest extractivist culture in western Brazilian Amazonia.
AB - The study sought to analyze clinical and epidemiological aspects of cutaneous
leishmaniasis (CL) in Xapuri, Acre, Brazil. Data from 2008 to 2014 registered in
the notification records of the disease of the Information System of the
Complaints of Notification (SINAN), and the data of the Information Department of
the Unified Health System (DATASUS) available from 2007 to 2013 were used and
analyzed in the light of the statistics of the temporal series by the Prais
Winsten method and chi-squared test. A total of 906 cases were registered with
60.2% occurring in men and 39.7% in women. The groups from 0 to 4 years of age
(48.0%) and from 5 to 19 years of age (23.3%) were the most affected. Regarding
the clinical forms, 77.7% presented CL and 22.3% mucocutaneous leishmaniasis
(MCL). Among the 896 cases with information on the diagnostic methods used,
Montenegro's skin test predominated (66.4%), with a positive result of 95.8% for
CL and 99.3% for MCL. Treatment with N-methylglucamine antimony was performed in
99.4% of the cases, but discontinuously used in the majority of patients. This
study presents information which may be used as a tool for the epidemiological
surveillance and control of the disease in Xapuri, a region which depends
essentially on forest resources and ecological tourism.
PMID- 28423088
TI - The epidemiology of cryptococcosis and the characterization of Cryptococcus
neoformans isolated in a Brazilian University Hospital.
AB - Cryptococcosis, a systemic disease caused by the fungus Cryptococcus neoformans/
Cryptococcus gattii is more severe in immunocompromised individuals. This study
aimed to analyze the epidemiology of the disease, the molecular characteristics
and the antifungal susceptibility of C. neoformans isolated from patients treated
in a Brazilian university hospital. This retrospective study was conducted in the
Clinical Hospital, Federal University of Uberlandia, and evaluated cases of
cryptococcosis and strains of C. neoformans isolated from 2004 to 2013. We
evaluated 41 patients, 85% of whom were diagnosed with AIDS. The fungus was
isolated from the cerebrospinal fluid (CSF) of 21 patients (51%); 19.5% had
fungemia and in 24% the agent was isolated from the CSF and blood, concurrently.
Meningoencephalitis was the most frequent (75%) manifestation of infection.
Despite adequate treatment, the mortality of the disease was 58.5%. Most isolates
(97.5%) presented the VNI genotype (serotype A, var. grubii) and one isolate was
genotyped as C. gattii (VGI); all the isolates were determined as mating type
MATa and showed susceptibility to the tested antifungals (fluconazole,
voriconazole, amphotericin B and 5-flucytosine). Although AIDS detection rates
remain stable, opportunistic infections such as cryptococcosis remain as major
causes of morbidity and mortality in these patients.
PMID- 28423089
TI - Phenotypic and genotypic detection of Candida albicans and Candida dubliniensis
strains isolated from oral mucosa of AIDS pediatric patients.
AB - The aim of this study was to assess a collection of yeasts to verify the presence
of Candida dubliniensis among strains isolated from the oral mucosa of AIDS
pediatric patients which were initially characterized as Candida albicans by the
traditional phenotypic method, as well as to evaluate the main phenotypic methods
used in the discrimination between the two species and confirm the identification
through genotypic techniques, i.e., DNA sequencing. Twenty-nine samples of C.
albicans isolated from this population and kept in a fungi collection were
evaluated and re-characterized. In order to differentiate the two species,
phenotypic tests (Thermotolerance tests, Chromogenic medium, Staib agar, Tobacco
agar, Hypertonic medium) were performed and genotypic techniques using DNA
sequencing were employed for confirmation of isolated species. Susceptibility and
specificity were calculated for each test. No phenotypic test alone was
sufficient to provide definitive identification of C. dubliniensis or C.
albicans, as opposed to results of molecular tests. After amplification and
sequencing of specific regions of the 29 studied strains, 93.1% of the isolates
were identified as C. albicans and 6.9% as C. dubliniensis. The Staib agar assay
showed a higher susceptibility (96.3%) in comparison with other phenotypic
techniques. Therefore, genotypic methods are indispensable for the conclusive
identification and differentiation between these species.
PMID- 28423090
TI - Scientometrics of zoonoses transmitted by the giant African snail Achatina fulica
Bowdich, 1822.
AB - The dissemination of the giant African snail Achatina fulica in several countries
has triggered a great number of studies on the mollusk, including those on
zoonoses related to health in humans. The current research is a scientific survey
on articles published in four databases, namely, PubMed, Bireme, Scielo and
Lilacs. Results indicate that Brazil has a prominent position in international
scientific production on this subject, with focus on Angiostrongylus cantonensis
occurrences.
PMID- 28423091
TI - An unusual abdominal wall mass in a child.
AB - Abdominal tumors are one of the most common types of pediatric cancer. Therefore,
they should always be included in the differential diagnosis of abdominal masses.
Here, we present the case of a child whose initial hypothesis of diagnosis
contemplated this possibility. Later, it was demonstrated that the abdominal mass
found was secondary to a common parasitosis. A 2-year old, moderately
malnourished and pale white boy was referred with a history of a rapidly growing,
well-limited, middle abdominal mass. The mass was 10 by 3 cm, hard and poorly
movable, apparently involving both abdominal rectus muscles. A complete resection
was performed, revealing an abdominal wall abscess, with intense eosinophilic
proliferation, secondary to a local and intense reaction to innumerous Ascaris
lumbricoides eggs. Extra luminal infestations with Ascaris, that usually form
peritoneal granulomas have been previously described. However, neither external
trauma nor fistula, that could explain the superficial presence of the eggs, was
found. This description reinforces the relevance of infectious diseases within
the differential diagnosis of abdominal masses, particularly in areas with high
prevalence of parasitic infestations.
PMID- 28423092
TI - What to expect from the 2017 yellow fever outbreak in Brazil?
PMID- 28423093
TI - Short and long term evaluation of the efficiency of PermaNet(r) 2.0 bed net
against environmental factors and washing using bioassay tests.
AB - The aim of the present study was to examine the resistance of PermaNet(r) 2.0 bed
nets against repeated washing and environmental factors by using bioassay tests.
After 5, 15 and 21 washings with detergents and by using bioassay tests, the
resistance of 40 PermaNet(r) 2.0 bed nets was compared with that of 40 bed nets
conventionally treated with one K-O tablet. To examine the long-term resistance,
31 PermaNet(r) 2.0 bed nets were also distributed among villagers, and were re
collected to perform bioassay tests after 1, 2 and 5 years. In the first phase of
this study, the insecticidal effect of the conventionally-treated nets
significantly decreased due to repeated washings (P < 0.001); however, it was not
significant regarding PermaNet(r) 2.0 bed nets (P = 0.92 in continuous exposure
and P = 0.12 in mortality tests). In the long-term phase of this study, the time
required for knockdown of PermaNet(r) 2.0 increased over the first 2 years and
then decreased. In addition, the mortality rate decreased over the first 2 years
and then increased. In conclusion, it seems that the technique used by the
manufacturer for impregnation of PermaNet(r) 2.0 bed nets has an acceptable
efficiency in comparison with conventional techniques.
PMID- 28423094
TI - Complications of chronic necrotizing pulmonary aspergillosis: review of published
case reports.
AB - Chronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary
aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons
with underlying pulmonary disease. These conditions are associated with high
morbidity and mortality and often require long-term antifungal treatment. The
long-term prognosis for patients with CNPA and the potential complications of
CNPA have not been well documented. The aim of this study was to review published
papers that report cases of CNPA complications and to highlight risk factors for
development of CNPA. The complications in conjunction associated with CNPA are as
follows: pseudomembranous necrotizing tracheobronchial aspergillosis, ankylosing
spondylarthritis, pulmonary silicosis, acute respiratory distress syndrome,
pulmonary Mycobacterium avium complex (MAC) disease, superinfection with
Mycobacterium tuberculosis, and and pneumothorax. The diagnosis of CNPA is still
a challenge. Culture and histologic examinations of bronchoscopically identified
tracheobronchial mucus plugs and necrotic material should be performed in all
immunocompromised individuals, even when the radiographic findings are unchanged.
Early detection of intraluminal growth of Aspergillus and prompt antifungal
therapy may facilitate the management of these patients and prevent development
of complications.
PMID- 28423095
TI - First reported case of fulminant TB with progression of infection from lungs to
the genitourinary region.
AB - Although tuberculosis (TB) is a curable disease, it continues to be one of the
leading infections associated with death in the world. Extra-pulmonary TB (EPTB)
occurs in approximately 10% of the total cases, presenting with lymph nodes,
pleura, bone and genitourinary tract as the most common locations. Genitourinary
tuberculosis, the second most common EPTB, is very difficult to diagnose unless
there is a high index of suspicion. Isolated TB orchitis or prostatitis without
clinical evidence of renal involvement is a rare entity among genitourinary
tuberculosis. We presented the first reported case of TB prostatitis and orchitis
associated with pulmonary TB and the presence of an acute massive caseous
pneumonia in an immunocompetent man. Despite the anti-TB therapy, the patient
presented a rapid progression of disease and deterioration of general conditions
taking to death, which occurred four days after TB treatment had started.
Disseminated TB is a relatively uncommon cause of acute massive caseous
pneumonia; however, there should always be suspicion of the disease, since it is
a potentially treatable cause. This rare case supports the assertion that TB
should be considered as an important differential diagnosis of genitourinary
tumors irrespective of evidence of active TB elsewhere in the body.
PMID- 28423096
TI - Perspectives on the Zika outbreak: herd immunity, antibody-dependent enhancement
and vaccine.
PMID- 28423097
TI - Guillain-Barre syndrome and dengue-like disease in 2015: temporal relationship in
Piaui state and implications on Zika virus surveillance.
PMID- 28423098
TI - ?
PMID- 28423099
TI - ?
PMID- 28423100
TI - ?
PMID- 28423101
TI - ?
PMID- 28423102
TI - ?
PMID- 28423103
TI - ?
PMID- 28423104
TI - ?
PMID- 28423105
TI - [Adolescense pregnancy in a marginalized rural community in Mexico].
AB - Objective:: To identify objective and subjective conditions in the lives of
pregnant teens within a highly-marginalized community in the state of Puebla,
Mexico. Materials and methods:: Objective and subjective conditions of pregnant
teens were evaluated through a mixed methodology (surveys, observation guides and
a structured interview guide). Results:: The main family characteristic is the
absence of a father due to migration, no desire to study or work and the new
meaning of pregnancy: the initial social stigma for engaging in a sexual activity
and then, the stigma for being a young mother. Conclusions:: Objective conditions
show family disintegration, lack of access to education at the community, high
school and college level as well as unemployment as processes linked to teen
pregnancy; thus, making it practically impossible to develop life goals.
Subjective conditions center around the reproduction of gender stereotypes
related to maternity.
PMID- 28423106
TI - [Comprehensive sexual education in Mexico: an analysis of coverage,
comprehensiveness and continuity of contents in Mexican public and private
schools].
AB - Objective:: To analyze coverage of comprehensive sex education (CSE) in high
schools in Mexico and describe whether it is comprehensive, homogeneous and has
continuity based on student reports of exposure to topics in three dimensions:
reproductive and sexual health, self-efficacy and rights and relations. Materials
and methods:: Within a probabilistic, cross-sectional survey with stratified,
cluster sampling, a nationally representative sample of 3 824 adolescents
attending 45 public and private high-schools in urban and rural areas completed
questionnaires on CSE. Results:: The proportion of adolescents reporting having
received sex education from school personnel varies depending on topics and grade
level. Topics most frequently covered are those related to sexual and
reproductive health while rights and relations are least frequently dealt with.
Most sex education topics are covered during junior high school and much less
frequently in elementary or high school. Conclusions:: CSE needs to be
comprehensive and homogenous in terms of content, ensure inclusion of priority
topics, meet national and international recommendations, ensure continuity and
adapt contents to student age through all education levels.
PMID- 28423107
TI - Health program in a Brazilian school.
AB - Objective:: To analyze the School Health Program (SHP) through the perceptions of
managers and health professionals. Materials and methods:: This was a
descriptive, cross-sectional, and qualitative study that conducted interviews
with 21 individuals using the lexical analysis of Bardin's speech and processed
the data through the Alceste software. Results:: In the interviewees' perception,
verification of blood pressure, visual acuity, weight, height, body mass index,
oral health, preventive actions and educational lectures are recommended in the
program's guidelines. The schools do not have available and adequate space for
the staff to perform the work. The predominant exchange occurs between the health
and education secretaries. The actions that provided opportunities to students
were primarily promotion, prevention, and health education; funding is the
responsibility of the Ministry of Health and Municipal Secretary of Health.
Conclusions:: The structures, exchanges, and available resources were
insufficient for the development of the program.
PMID- 28423108
TI - [Potential health risks from consumption of water with arsenic in Colima,
Mexico].
AB - Objective:: To estimate potential health risks due to chronic ingestion of
arsenic from groundwater in Colima, Mexico. Materials and methods:: Samples were
randomly taken in 36 wells from 10 local aquifers. Analysis was performed by ICP
OES following international standards. Geostatistical interpolation was performed
with ArcGIS, implementing a model weighting inverse distance to estimate arsenic
routes of exposure and consumption on each locality. The Hazard Quotient Ratio
(HQ) and carcinogenic risk (R) for As were estimated. Results:: The weighted
average HQ for arsenic in Colima is 2.41. There are HQ> 1 values indicating
adverse non-cancer health effects by continuous and prolonged intake of water
with arsenic, which could affect 183 832 individuals in the state. The risk of
developing any type of cancer among the population in this study due to high
arsenic concentrations in groundwater (R) is 1.089E-3, which could statistically
cause 446 cases of cancer. Conclusions:: Current levels of arsenic in groundwater
increase carcinogenic and non-carcinogenic human health risks in Colima.
PMID- 28423109
TI - Effects of climatic and social factors on dengue incidence in Mexican
municipalities in the state of Veracruz.
AB - Objective:: To assess links between the social variables and longer-term El Nino
Southern Oscillation (ENSO) related weather conditions as they relate to the week
to-week changes in dengue incidence at a regional level. Materials and methods::
We collected data from 10 municipalities of the Olmeca region in Mexico, over a
10 year period (January 1995 to December 2005). Negative binomial models with
distributed lags were adjusted to look for associations between changes in the
weekly incidence rate of dengue fever and climate variability. Results:: Our
results show that it takes approximately six weeks for sea surface temperatures
(SST -34) to affect dengue incidence adjusted by weather and social variables.
Conclusion:: Such models could be used as early as two months in advance to
provide information to decision makers about potential epidemics. Elucidating the
effect of climatic variability and social variables, could assist in the
development of accurate early warning systems for epidemics like dengue,
Chikungunya and Zika.
PMID- 28423110
TI - ?
AB - Objective:: We aimed to explore organ donation and transplantation in Mexico from
the point of view of transplantation health professionals. Materials and
methods:: A qualitative study was carried out. Twenty six organ transplantation
health professionals from seven states of Mexico participated. Semi-structured
face-to-face interviews were conducted mainly in hospital settings. Critical
discourse analysis was performed. Results:: According to participants, living
organ transplantation offers benefits for recipients as well as for donors.
Several factors influence the field of transplantation negatively, among them the
scarcity of resources that impedes the incorporation of new health personnel, as
well as conflicts between transplantation teams with diverse health professionals
and authorities. Conclusion:: Besides increasing economic resources,
transplantation health personnel should be sensitized to find solutions in order
to avoid conflicts with different health professionals. Studies on organ donation
and transplants also should include other social actors' viewpoint.
PMID- 28423111
TI - [What is purchased, how and from whom by Seguro Popular in Mexico? Experience
with strategic purchasing at national level and in a pioneer institution].
AB - Objective:: To analyze the scope of demand subsidies through strategic purchasing
of health services. Materials and methods:: Interviews and document analyses at
national level and a case study of the state of Hidalgo. Results:: SPSS
explicitly prioritizes interventions to be financed and regulates prices and
expenditure ceilings. Public providers are predominantly funded through the
purchasing of inputs and the contracting of human resources, in the absence of
competition and with a low degree of managerial autonomy. Seguro Popular in
Hidalgo has diversified service providers and payment mechanisms. Conclusions::
SPSS has ample opportunity to extend and deepen strategic purchasing. Greater
decision-making autonomy of payers and providers is required, as well as
regulations to promote provider networks in competitive environments.
PMID- 28423112
TI - Prevalence trends of wood use as the main cooking fuel in Mexico, 1990-2013.
AB - Objective:: To determine prevalence trends of using Wood as the Main Cooking Fuel
(WMCF) in Mexico and household characteristics that predict its use. Materials
and methods:: Estimates were obtained from the 1990, 2000 and 2010 censuses and
from a national survey performed in 2012 and 2013. Results:: In 2012-2013, 9.5%
of the 66 321 surveyed households and 10.9% of their 252 011 residents used WMCF.
Prevalence was higher in rural (40.5%) than urban areas (1.5%), p<0.0001. From
1990 to 2013 wood use decreased by 53% overall and by 28.6% in rural areas, gas
use increased respectively by 17.5 and 52.7%. Predictors of using WMCF were
living in rural or suburban areas and those associated with low socioeconomic
status. Conclusion:: Use of WMCF has decreased substantially in Mexico but at a
slower pace in rural areas. Improving household characteristics and socioeconomic
status may decrease use of WMCF at a higher rate.
PMID- 28423113
TI - Time trends for tobacco and alcohol use in youth-rated films popular in Mexico
and Argentina, from 2004-2012.
AB - Objective:: To examine and compare overall prevalence and time trends in tobacco
and alcohol portrayals and brand appearances in youth-rated US and nationally
produced films that were the most successful in Argentina and Mexico from 2004
2012. Materials and methods:: Top-grossing nationally produced films from
Argentina (n=73), Mexico (n=85) and the US (n=643) were content analyzed.
Logistic regression was used to determine differences between Mexican, Argentine
and US produced films. Linear regression models assessed significant cross
country differences in the mean number of tobacco and alcohol seconds. Results::
Films from Mexico and Argentina were more likely than US films to contain
tobacco, (OR=4.2; p<0.001) and (OR=7.2; p<0.001). Alcohol was present in 93% of
Argentine, 83% in Mexican and 83% US films. Conclusions:: Smoking and alcohol
were highly prevalent in nationally produced films. They may have a significant
impact and should be targeted by policies to reduce youth exposure to portrayals
of risk behaviors.
PMID- 28423114
TI - Human papillomavirus vaccine efficacy in the prevention of anogenital warts:
systematic review and meta-analysis.
AB - Objective:: To review evidence on the efficacy of HPV vaccines in the prevention
of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis
and oral papillomatosis). Materials and methods:: We conducted a systematic
review of randomized trials. We performed random effect models and effects were
reported as relative risks (RR) and their confidence intervals (95%CI) following
both intention to treat (ITT) and per protocol (PP) analyses. Results:: We
included six studies (n=27 078). One study was rated as high risk of bias. One
study could not be included in the meta-analysis because it provided combined
results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR:
0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05,
95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in
women or with low-risk of bias provided similar results. Conclusion:: HPV
quadrivalent vaccine is efficacious in preventing AGW in men and women.
PMID- 28423115
TI - Analysis of cigarette demand in Argentina: the impact of price changes on
consumption and government revenues.
AB - Objective:: To estimate cigarette demand and to simulate a tax policy targeted to
reduce tobacco consumption. Materials and methods:: Demand was estimated using a
vector error correction model. Simulation exercises present the impact of a tax
increase on consumption and revenues. Results:: Changes in real income and the
real price of cigarettes affect the demand for cigarettes in Argentina. The long
term price elasticity is 0.279 (a 10% increase in real prices reduces cigarette
consumption by 2.79% per quarter) and the long term income elasticity is 0.411 (a
10% increase in real income raises consumption by 4.11% per quarter). Even in a
conservative scenario, simulations show that increasing the price of cigarettes
by 100% using excise taxes would maximize revenues and reduce cigarette
consumption. Conclusion:: There is sufficient room to increase taxes, reducing
cigarette consumption, while still increasing tax revenues.
PMID- 28423116
TI - [Experiences of street harassment and associations with perceptions of social
cohesion among women in Mexico City].
AB - Objective:: To document the frequency and forms of street harassment and examine
the association between street harassment experiences and perceptions of social
cohesion. Materials and methods:: Baseline survey data collected among women
seeking care in public health clinics in Mexico City were used for analysis.
Results:: Nearly two-thirds (62.8%) of women reported experiencing some form of
street harassment in the prior month; women with street harassment experiences
reported significantly lower perceived social cohesion (b=-0.46; 95%CI: -0.69,
0.22). Conclusions: : Findings indicate reducing street harassment may have
important implications for improving women's perceived social cohesion and their
safety in Mexico City.
PMID- 28423117
TI - [Recommendations for a multisectorial national policy to promote breastfeeding in
Mexico: position of the National Academy of Medicine].
AB - Evidence strongly supports that to improve breastfeeding practices it is needed
to strengthen actions of promotion, protection and support. To achieve this goal,
it is necessary to establish a multisectoral national policy that includes
elements such as design, implementation, monitoring and evaluation of programs
and policies, funding research, advocacy to develop political willingness, and
the promotion of breastfeeding from the national to municipal level, all
coordinated by a central level. It is until now that Mexico has initiated a
reform process to the establish a National Strategy for Breastfeeding Action.
This strategy, is the result not only of the consistent scientific evidence on
clear and strong benefits of breastfeeding on population health and the
development of human capital, but also for the alarming data of deterioration of
breastfeeding practices in the country. The comprehensive implementation of the
National Strategy for Breastfeeding Action that includes the establishment of a
national committee, intra- and inter-sectoral coordination of actions, setting
clear goals and monitoring the International Code of Marketing of Breast-Milk
Substitutes, is the awaiting responsibility of the public health agenda of the
country.
PMID- 28423118
TI - Obesity and kidney disease: hidden consequences of the epidemic.
AB - Obesity has become a worldwide epidemic and its prevalence has been projected to
grow by 40% in the next decade. This increasing prevalence has implications for
the risk of diabetes, cardiovascular disease and also for chronic kidney disease
(CKD). A high body mass index is one of the strongest risk factors for new-onset
CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to
meet the heightened metabolic demands of the increased body weight. The increase
in intraglomerular pressure can damage the kidneys and raise the risk of
developing CKD in the long-term. The incidence of obesity-related glomerulopathy
has increased ten-fold in recent years. Obesity has also been shown to be a risk
factor for nephrolithiasis, and for a number of malignancies including kidney
cancer. This year, the World Kidney Day will promote education on the harmful
consequences of obesity and its association with kidney disease, advocating
healthy lifestyle and health policy measures that make preventive behaviors an
affordable option.
PMID- 28423119
TI - Importance of SERCA2a on early isolated diastolic dysfunction induced by
supravalvular aortic stenosis in rats.
AB - Cardiac remodeling is defined as changes in shape and function of the heart in
response to aggression (pressure overload). The sarcoplasmic reticulum calcium
ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A
wide spectrum of studies report a decrease in SERCA2a in heart failure, but none
evaluate it's the role in early isolated diastolic dysfunction in supravalvular
aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such
dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and
Sham groups, which were submitted to surgery with or without aorta clipping,
respectively. After 6 weeks, the animals were submitted to echocardiogram and
functional analysis by isolated papillary muscle (IPM) in basal condition,
hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations
of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and
phospholamban detection. Data analysis was carried out with Student's t-test and
ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection
fraction. Basal condition in IPM showed similar increases in developed tension
(DT) and resting tension (RT) in AoS, and hypoxia was similar between groups.
After cyclopiazonic acid blockage, final DT was equally decreased and RT was
similar between groups, but the speed of relaxation was decreased in the AoS
group. Western-blot was uniform in all evaluations. The hypothesis was confirmed,
since functional parameters regarding SERCA2a were changed in the AoS group.
PMID- 28423120
TI - Primary cultures of mouse small intestinal epithelial cells using the
dissociating enzyme type I collagenase and hyaluronidase.
AB - The epithelium is a highly dynamic system, which plays a crucial role in the
homeostasis of the intestinal tract. However, studies on the physiological and
pathophysiological functions of intestinal epithelial cells (IECs) have been
hampered due to lack of normal epithelial cell models. In the present study, we
established a reproducible method for primary culture of mouse IECs, which were
isolated from the viable small intestinal crypts of murine fetuses (on embryonic
day 19), using type I collagenase and hyaluronidase in a short span of time (<=20
min). With this method, continuously growing mouse IECs, which can be subcultured
over a number of passages, were obtained. The obtained cell lines formed a tight
cobblestone-like arrangement, displayed long and slender microvilli, expressed
characteristic markers (cytokeratin 18 and Notch-1), and generated increasing
transepithelial electrical resistance and low paracellular permeability during in
vitro culture. The cells also had enzymatic activities of alkaline phosphatase
and sucrase-isomaltase, and secreted various cytokines (IL-1beta, IL-6, IL-8, and
monocyte chemoattractant protein-1), responding to the stimulation of Escherichia
coli. These results show that the primary-cultured mouse IECs obtained by the
method established here had the morphological and immunological characteristics
of IECs. This culture system can be a beneficial in vitro model for studies on
mucosal immunology and toxicology.
PMID- 28423121
TI - Telomere length analysis in monoclonal B-cell lymphocytosis and chronic
lymphocytic leukemia Binet A.
AB - Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic clinical entity
characterized by the proliferation of monoclonal B cells not meeting the
diagnosis criteria for chronic lymphocytic leukemia (CLL). MBL may precede the
development of CLL, but the molecular mechanisms responsible for disease
progression and evolution are not completely known. Telomeres are usually short
in CLL and their attrition may contribute to disease evolution. Here, we
determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy
volunteers. Twenty-one CLL patients, 11 subjects with high-count MBL, and 6 with
low-count MBL were enrolled. Two hundred and sixty-one healthy volunteers aged 0
to 88 years were studied as controls. After diagnosis confirmation, a flow
cytometry CD19+CD5+-based cell sorting was performed for the study groups.
Telomere length was determined by qPCR. Telomere length was similar in the 3
study groups but shorter in these groups compared to normal age-matched subjects
that had been enrolled in a previous study from our group. These findings suggest
that telomere shortening is an early event in CLL leukemogenesis.
PMID- 28423122
TI - Development and Validation of a Stratification Tool for Predicting Risk of Deep
Sternal Wound Infection after Coronary Artery Bypass Grafting at a Brazilian
Hospital.
AB - Objective: Deep sternal wound infection following coronary artery bypass grafting
is a serious complication associated with significant morbidity and mortality.
Despite the substantial impact of deep sternal wound infection, there is a lack
of specific risk stratification tools to predict this complication after coronary
artery bypass grafting. This study was undertaken to develop a specific
prognostic scoring system for the development of deep sternal wound infection
that could risk-stratify patients undergoing coronary artery bypass grafting and
be applied right after the surgical procedure. Methods: Between March 2007 and
August 2016, continuous, prospective surveillance data on deep sternal wound
infection and a set of 27 variables of 1500 patients were collected. Using binary
logistic regression analysis, we identified independent predictors of deep
sternal wound infection. Initially we developed a predictive model in a subset of
500 patients. Dataset was expanded to other 1000 consecutive cases and a final
model and risk score were derived. Calibration of the scores was performed using
the Hosmer-Lemeshow test. Results: The model had area under Receiver Operating
Characteristic (ROC) curve of 0.729 (0.821 for preliminary dataset). Baseline
risk score incorporated independent predictors of deep sternal wound infection:
obesity (P=0.046; OR 2.58; 95% CI 1.11-6.68), diabetes (P=0.046; OR 2.61; 95% CI
1.12-6.63), smoking (P=0.008; OR 2.10; 95% CI 1.12-4.67), pedicled internal
thoracic artery (P=0.012; OR 5.11; 95% CI 1.42-18.40), and on-pump coronary
artery bypass grafting (P=0.042; OR 2.20; 95% CI 1.13-5.81). A risk
stratification system was, then, developed. Conclusion: This tool effectively
predicts deep sternal wound infection risk at our center and may help with risk
stratification in relation to public reporting and targeted prevention strategies
in patients undergoing coronary artery bypass grafting.
PMID- 28423124
TI - The Importance of Peer-Reviewers. How to Recognize their Merits?
PMID- 28423123
TI - N-acetylcysteine versus Dopamine to Prevent Acute Kidney Injury after Cardiac
Surgery in Patients with Preexisting Moderate Renal Insufficiency.
AB - Objective: Acute kidney injury after cardiac surgery is associated with mortality
and morbidity. Therefore, strategies to prevent acute kidney injury are very
important. The aim of this placebo-controlled randomized double-blind study was
to compare the prophylactic efficacy of N-Acetylcysteine and dopamine
administration in patients with pre-existing moderate renal insufficiency who
were undergoing cardiopulmonary bypass. Methods: This study included 135 patients
with pre-existing moderate renal insufficiency who were scheduled for coronary
artery bypass grafting surgery. Serum creatinine and GFR were recorded
preoperatively and on the first and second postoperative days. Results: On the
first and second postoperative days, the drugs used showed statistically
significant differences among the creatinine groups (P<0.001). According to
Tukey's HSD, on the first and second PO, the creatinine of Group N, D and P were
significantly different (P<0.001). On the first and second PO, the used drugs
showed statistically significant differences among the effects of eGFR (P<0.001).
According to Tukey's HSD on the first postoperative day, the average eGFR score
of Group N compared to D and P were significantly difference (P<0.001). On the
second postoperative day, the eGFR of Group N and D showed no difference
(P=0.37), but P showed a difference (P<0.001). Conclusion: We found that the
prophylactic use of intravenous N-Acetylcysteine had a protective effect on renal
function, whereas the application of renal dose dopamine did not have a
protective effect in patients with pre-existing moderate renal failure.
PMID- 28423126
TI - Chronic Atrial Fibrillation Ablation with Harmonic Scalpel during Mitral Valve
Surgery.
AB - Objective: To evaluate surgical treatment of chronic atrial fibrillation with
ultrasound in patients with mitral valve disease, considering preoperative
clinical characteristics of patients undergoing surgical procedure and follow-up
in the immediate postoperative period, in hospital and up to 60 months after
discharge. Methods: We studied 100 patients with chronic atrial fibrillation and
mitral valve disease who underwent surgical treatment using ultrasound ablation.
Patient data were reviewed by consulting the control reports, including signs and
symptoms, underlying disease, functional class, hospital stay, surgical procedure
time, ablation time, immediate complications, and complications at discharged and
up to 60 months later. Actuarial curve (Kaplan-Meier) was used for the study of
permanence without recurrence after 12, 24, 36, 48 and 60 months. Results: 86% of
the patients had rheumatic mitral valve disease, 14% had degeneration of the
mitral valve, 40% had mitral regurgitation, and 36% had mitral stenosis. Main
symptoms included palpitations related to tachycardia by chronic atrial
fibrillation (70%), congestive heart failure (70%), and previous episodes of
acute pulmonary edema (27%). Early results showed that 94% of the patients
undergoing ultrasound ablation reversed the rate of chronic atrial fibrillation,
86% being in sinus rhythm and 8% in atrioventricular block. At hospital
discharge, maintenance of sinus rhythm was observed in 86% of patients and there
was recurrence of chronic atrial fibrillation in 8% of patients. At follow-up
after 60 months, 83.8% of patients maintained the sinus rhythm. Conclusion:
Surgical treatment of chronic atrial fibrillation with ultrasound concomitant
with mitral valve surgery is feasible and satisfactory, with maintenance of sinus
rhythm in most patients (83.8%) after 60 months of follow-up.
PMID- 28423125
TI - Coronary Arteriovenous Fistulas in Adult Patients: Surgical Management and
Outcomes.
AB - Objective: The aim of this study was to describe the demographic, clinical and
anatomic characteristics of coronary arteriovenous fistulas in adult patients who
underwent open cardiac surgery and to review surgical management and outcomes.
Methods: Twenty-one adult patients (12 female, 9 male; mean age: 56.1+/-7.9
years) who underwent surgical treatment for coronary arteriovenous fistulas were
retrospectively included in this study. Coronary angiography, chest X-ray,
electrocardiography and transthoracic echocardiography were preoperatively
performed in all patients. Demographic and clinical data were also collected.
Postoperative courses of all patients were monitored and postoperative
complications were noted. Results: A total of 25 coronary arteriovenous fistulas
were detected in 21 patients; the fistulas originated mainly from left anterior
descending artery (n=9, 42.8%). Four (19.4%) patients had bilateral fistulas
originating from both left anterior descending and right coronary artery. The
main drainage site of coronary arteriovenous fistulas was the pulmonary artery
(n=18, 85.7%). Twelve (57.1%) patients had isolated coronary arteriovenous
fistulas and 4 (19.4%), concomitant coronary artery disease. Twenty (95.3%) of
all patients were symptomatic. Seventeen patients were operated on with and 4
without cardiopulmonary bypass. There was no mortality. Three patients had
postoperative atrial fibrillation. One patient had pericardial effusion causing
cardiac tamponade who underwent reoperation. Conclusion: The decision of surgical
management should be made on the size and the anatomical location of coronary
arteriovenous fistulas and concomitant cardiac comorbidities. Surgical closure
with ligation of coronary arteriovenous fistulas can be performed easily with on
pump or off-pump coronary artery bypass grafting, even in asymptomatic patients
to prevent fistula related complications with very low risk of mortality and
morbidity.
PMID- 28423127
TI - Evaluation of Anomalous Coronary Arteries from the Pulmonary Artery.
AB - Objective: This study evaluated clinical and diagnostic findings, treatment
methods, and follow-up of cases of anomalous coronary arteries from the pulmonary
artery. Methods: The study included all cases diagnosed with anomalous coronary
arteries from the pulmonary artery between January 2012 and January 2016. Data
from patients' demographic characteristics, electrocardiography,
echocardiography, angiographic findings, operation, intensive care unit stay, and
follow-up were evaluated. Results: The study included 12 patients (8 male, 4
female), 10 with anomalous left coronary artery from the pulmonary artery
(ALCAPA) and 2 with anomalous right coronary artery from the pulmonary artery
(ARCAPA). Median age at diagnosis was 4 months (range, 1 month - 10 years old)
and median weight was 5.5 kg (range, 3-30 kg). The most common complaints were
murmur (n=7) and respiratory distress (n=5). In 4 cases, the initial diagnosis
was dilated cardiomyopathy. Electrocardiographs were pathologic in all cases.
Echocardiographic examination revealed medium to severe mitral valve
regurgitation in 4 cases and reduced (< 40%) ejection fraction in 6 patients. Of
the 12 patients, 8 underwent direct implantation of the left coronary artery into
the aorta, 2 underwent implantation of the right coronary artery into the aorta,
and the remaining 2 underwent a Takeuchi procedure. There were no early
mortalities. Median hospital stay was 20 days (range, 5-35 days). Median follow
up duration was 18 months (range, 5-36 months), and no cases required further
surgery during follow-up. Conclusions: Anomalous coronary arteries from the
pulmonary artery can be successfully repaired providing there is early diagnosis
and effective, appropriate intensive care unit follow-up. Therefore, coronary
artery origins should be evaluated carefully, especially in cases with dilated
cardiomyopathies.
PMID- 28423128
TI - Peratrial Device Closure of Atrial Septal Defect Under Transesophageal
Echocardiographic Guidance without Fluoroscopy Compared to Conventional On-Pump
Surgical Closure.
AB - Objective: This study is designed to evaluate the advantages between peratrial
device closure under transesophageal echocardiographic guidance and open heart
surgery in atrial septal defect. Methods: From November 2011 to September 2014,
28 patients with atrial septal defect were treated. Fourteen patients received
peratrial device closure under transesophageal echocardiographic guidance (TEE
group) and 14 patients received cardiopulmonary bypass (CPB group). Clinical
parameters during intraoperative and postoperative periods were examined.
Results: All patients recovered after surgery without serious complications.
Compared with that in CPB group, clinical observations in TEE group showed
significant decreases in the operation time (193.6+/-35.5 vs. 77.4+/-22.7 min,
P<0.05), periods in intensive care unit (31.6+/-23.3 vs. 17.5+/-8.1 hours,
P<0.05), fluid volume after operation (502.5+/-439.3 vs. 32.5+/-7.3 ml, P<0.05),
postoperative length of hospital stay (8.9+/-2.8 vs. 6.8+/-2.4 days, P<0.05) and
total hospitalization cost (7205.9+/-1617.6 vs. 5882.3+/-441.2 $, P<0.05).
Conclusion: The peratrial device closure of atrial septal defect under
transesophageal echocardiographic guidance is a mini-invasive, simple, safe and
effective intervention. Its use in the clinical practice should be encouraged.
PMID- 28423129
TI - Totally Percutaneous Access Using Perclose Proglide for Endovascular Treatment of
Aortic Diseases.
AB - Objective: To evaluate our experience following the introduction of a
percutaneous program for endovascular treatment of aortic diseases using Perclose
Proglide(r) assessing efficacy, complications and identification of potential
risk factors that could predict failure or major access site complications.
Methods: A retrospective cohort study during a two-year period was performed. All
the patients submitted to totally percutaneous endovascular repair (PEVAR) of
aortic diseases and transcatheter aortic valve implantation since we started the
total percutaneous approach with the preclosure technique from November 2013 to
December 2015 were included in the study. The primary endpoint was major
ipsilateral access complication, defined according to PEVAR trial. Results: In a
cohort of 123 patients, immediate technical success was obtained in 121 (98.37%)
patients, with only two (0.82%) cases in 242 vascular access sites that required
intervention immediately after the procedure. Pairwise comparisons revealed
increased major access complication among patients with >50% common femoral
artery (CFA) calcification vs. none (P=0.004) and > 50% CFA calcification vs. <
50% CFA calcification (P=0.002). Small artery diameter (<6.5 mm) also increased
major access complication compared to bigger diameters (> 6.5 mm) (P=0.027).
Conclusion: The preclosure technique with two Perclose Proglide(r) for PEVAR is
safe and effective. Complications occur more often in patients with unfavorable
access site anatomy and the success rate can be improved with proper patient
selection.
PMID- 28423130
TI - Bovine Pericardial Patch Augmentation of One Insufficient Aortic Valve Cusp with
Twenty-three-year Positive Clinical Follow-up Independent of the Patch
Degeneration.
AB - Scientific progress shall ultimately boost the current acceptance level for
conservative aortic valve surgery. The present text aimed to report the 23-year
long-term follow-up of one patient operated with bovine pericardium cusp
extension. Growing confidence in the efficacy of the operation will allow a more
expeditious indication for surgical treatment, as is already the case in mitral
valve repair. This change of attitude will certainly make it possible for
patients to be sent for operation in mild aortic valve regurgitation. The present
report reinforces the concept and highlights the impression that the aortic
valvoplasty, independent of the progressive bovine pericardium degeneration, may
positively change the natural history of the aortic valve insufficiency.
PMID- 28423131
TI - Thoracoabdominal Aortic Aneurysm in a HIV-positive Patient.
AB - Advent of antiretroviral therapy has increased survival of patients with human
immunodeficiency virus (HIV) infections, with the result that some of these
patients now develop degenerative diseases, such as atherosclerotic aneurysms.
Degenerative thoracoabdominal aortic aneurysm is rare in HIV patients. In this
report, a 63-year-old male patient with HIV submitted to open repair of
thoracoabdominal aortic aneurysm. The patient did not suffer any type of
complication in the perioperative period and remained well in a 28-month follow
up period. In summary, open repair still remains a good alternative for aortic
complex aneurysms even in HIV patients.
PMID- 28423132
TI - Repair of Penetrating Pericardial and Diaphragmatic Injury with Cormatrix(r)
Patch in a Case of Suicide Attempt.
AB - The authors report the case of a suicide attempt. A 59-year-old man with self
inflicted penetrating chest trauma underwent emergency cardiothoracic surgery.
Pre-operative computed tomography scan showed critical proximity between the
blade and the right ventricle. Intraoperative findings showed a pericardial
laceration and a huge diaphragmatic lesion with heart and abdominal organs
integrity. The diaphragm muscle was repaired with a CorMatrix(r) patch, an
acceptable alternative to the traditional synthetic mesh avoiding infection and
repeated herniation.
PMID- 28423133
TI - The Importance of the Proper Definition of Adulthood: What is and What is Not
Included in a Scientific Publication.
PMID- 28423134
TI - Infant mortality by color or race from Rondonia, Brazilian Amazon.
AB - OBJECTIVE: To analyze the quality of records for live births and infant deaths
and to estimate the infant mortality rate for skin color or race, in order to
explore possible racial inequalities in health. METHODS: Descriptive study that
analyzed the quality of records of the Live Births Information System and
Mortality Information System in Rondonia, Brazilian Amazonian, between 2006-2009.
The infant mortality rates were estimated for skin color or race with the direct
method and corrected by: (1) proportional distribution of deaths with missing
data related to skin color or race; and (2) application of correction factors. We
also calculated proportional mortality by causes and age groups. RESULTS: The
capture of live births and deaths improved in relation to 2006-2007, which
required lower correction factors to estimate infant mortality rate. The risk of
death of indigenous infant (31.3/1,000 live births) was higher than that noted
for the other skin color or race groups, exceeding by 60% the infant mortality
rate in Rondonia (19.9/1,000 live births). Black children had the highest
neonatal infant mortality rate, while the indigenous had the highest post
neonatal infant mortality rate. Among the indigenous deaths, 15.2% were due to
ill-defined causes, while the other groups did not exceed 5.4%. The proportional
infant mortality due to infectious and parasitic diseases was higher among
indigenous children (12.1%), while among black children it occurred due to
external causes (8.7%). CONCLUSIONS: Expressive inequalities in infant mortality
were noted between skin color or race categories, more unfavorable for indigenous
infants. Correction factors proposed in the literature lack to consider
differences in underreporting of deaths for skin color or race. The specific
correction among the color or race categories would likely result in exacerbation
of the observed inequalities. OBJETIVO: Analisar a qualidade dos registros de
nascidos vivos e de obitos infantis e estimar a taxa de mortalidade infantil
segundo cor ou raca, a fim de explorar iniquidades etnico-raciais em saude.
METODOS: Estudo descritivo que analisou a qualidade dos registros do Sistema de
Informacoes sobre Nascidos Vivos e do Sistema de Informacoes sobre Mortalidade em
Rondonia, Amazonia brasileira, entre 2006-2009. As taxas de mortalidade infantil
foram estimadas nas categorias de cor ou raca, pelo metodo direto, e corrigidas
por: (1) distribuicao proporcional dos obitos com cor ou raca ignorada; e (2)
aplicacao de fatores de correcao. Efetuou-se tambem o calculo da mortalidade
proporcional por causas e grupos etarios. RESULTADOS: Entre 2008-2009, a captacao
de nascimentos e obitos melhorou em relacao aos anos de 2006-2007, requerendo
fatores de correcao menores para estimar a taxa de mortalidade infantil. O risco
de morte de criancas indigenas (31,3/1.000 nascidos vivos) foi maior que o
registrado nos demais grupos de cor ou raca, excedendo em 60% a mortalidade
infantil media no estado (19,9/1.000 nascidos vivos). As criancas pretas
apresentaram as maiores taxas de mortalidade infantil neonatal, enquanto as
indigenas apresentaram as maiores taxas de mortalidade infantil pos-neonatal.
Observou-se que 15,2% dos obitos indigenas foram por causas mal definidas,
enquanto nos demais grupos nao ultrapassaram 5,4%. A mortalidade infantil
proporcional por doencas infecciosas e parasitarias foi maior entre indigenas, ao
passo que entre criancas pretas, sobressairam as causas externas (8,7%).
CONCLUSOES: Observaram-se expressivas iniquidades na mortalidade infantil entre
as categorias de cor ou raca, com situacao mais desfavoravel as criancas
indigenas. Os fatores de correcao propostos na literatura nao consideram
diferencas na subenumeracao de obitos entre as categorias de cor ou raca. A
correcao especifica entre as categorias de cor ou raca provavelmente resultaria
em exacerbacao das iniquidades observadas.
PMID- 28423135
TI - Childhood cancer and environmental integrity: a commentary and a proposal.
AB - Improvements in the health standards of developed and developing societies depend
primarily on the relationships between economy and environment. Recent long-term
changes in the chemical composition of man-made environments may be linked to
changes in the biology of human beings. Here we argue that children are at the
greatest risk of being affected by the dangerous effects of these changes, with
particular reference to cancer. The concept of cancer risk must be extended to
new contexts. Considering the increasing rates of chemical pollution and its
spreading in the environment, we illustrate a proposal aiming to protect the
human health, in an intra- and intergenerational perspective. A surveillance
system of occupational and residential exposures should be implemented to prevent
cancer risk in embryos and children.
PMID- 28423136
TI - Violence against women, Espirito Santo, Brazil.
AB - OBJECTIVE: To estimate the prevalence and factors associated with psychological,
physical and sexual violence in women victims of intimate partner violence
assisted in the primary care services. METHODS: This is a cross-sectional study,
conducted in 26 health units in Vitoria, State of Espirito Santo, from March to
September 2014. We interviewed 991 women aged 20-59 years. To classify the
psychological, physical and sexual violence, the World Health Organization
instrument on violence against women was used and a questionnaire to investigate
the sociodemographic, behavioral characteristics, and the women's family and life
history was developed. The statistical analyzes used were Poisson regression,
Fisher's exact test and Chi-square. RESULTS: The prevalence we observed were
psychological 25.3% (95%CI 22.6-28.2); physical 9.9% (95%CI 8.1-11.9) and sexual
5.7% (95%CI 4.3-7.3). Psychological violence remained associated with education,
marital status, maternal history of intimate partner violence, sexual violence in
childhood and drug use, while physical assault was related to age, education,
marital status and maternal history of intimate partner violence. Sexual violence
occurred the most among women with low income, and victims of sexual violence in
childhood. CONCLUSIONS: Psychological, physical and sexual violence showed highly
frequency among women assisted by primary care services. Sociodemographic and
behavioral factors, personal experiences, and maternal violence influence the
phenomenon. OBJETIVO: Estimar a prevalencia e os fatores associados as violencias
psicologica, fisica e sexual nas mulheres vitimas de violencia perpetrada pelo
parceiro intimo atendidas nos servicos de atencao primaria. METODOS: Estudo
transversal, realizado em 26 unidades de saude do municipio de Vitoria, no
Espirito Santo, de marco a setembro de 2014. Foram entrevistadas 991 usuarias de
20 a 59 anos. Para classificar as violencias psicologica, fisica e sexual foi
utilizado o instrumento da Organizacao Mundial de Saude sobre violencia contra a
mulher e um questionario foi elaborado para investigar as caracteristicas
sociodemograficas, comportamentais e de historia familiar e de vida da mulher. As
analises estatisticas utilizadas foram: regressao de Poisson, teste exato de
Fisher e Qui-quadrado. RESULTADOS: As prevalencias observadas foram: psicologica
25,3% (IC95% 22,6-28,2); fisica 9,9% (IC95% 8,1-11,9) e sexual 5,7% (IC95% 4,3
7,3). A violencia psicologica manteve-se associada a escolaridade, situacao
conjugal, historico materno de violencia por parceiro intimo, violencia sexual na
infancia e ter feito uso de drogas, enquanto a agressao fisica esteve relacionada
a idade, escolaridade, situacao conjugal e a historia materna de violencia por
parceiro intimo. A violencia sexual foi mais frequente nas mulheres de menor
renda e que sofreram abuso sexual na infancia. CONCLUSOES: As violencias
psicologica, fisica e sexual apresentaram alta magnitude entre as mulheres
usuarias dos servicos de atencao primaria de saude. Fatores sociodemograficos,
comportamentais e experiencias pessoal e materna de violencia influenciam a
ocorrencia do fenomeno.
PMID- 28423137
TI - Psychometric properties of the Vulnerability to Abuse Screening Scale for
screening abuse of older adults.
AB - OBJECTIVE: Adapt and evaluate the psychometric properties of the Vulnerability to
Abuse Screening Scale to identify risk of domestic violence against older adults
in Brazil. METHODS: The instrument was adapted and validated in a sample of 151
older adults from a geriatric reference center in the municipality of Belo
Horizonte, State of Minas Gerais, in 2014. We collected sociodemographic,
clinical, and abuse-related information, and verified reliability by
reproducibility in a sample of 55 older people, who underwent re-testing of the
instrument seven days after the first application. Descriptive and comparative
analyses were performed for all variables, with a significance level of 5%. The
construct validity was analyzed by the principal components method with a
tetrachoric correlation matrix, the reliability of the scale by the weighted
Kappa (Kp) statistic, and the internal consistency by the Kuder-Richardson
estimator formula 20 (KR-20). RESULTS: The average age of the participants was
72.1 years (DP = 6.96; 95%CI 70.94-73.17), with a maximum of 92 years, and they
were predominantly female (76.2%; 95%CI 69.82-83.03). When analyzing the
relationship between the scores of the Vulnerability to Abuse Screening Scale,
categorized by presence (score > 3) or absence (score < 3) of vulnerability to
abuse, with clinical and health conditions, we found statistically significant
differences for self-perception of health (p = 0.002), depressive symptoms (p =
0.000), and presence of rheumatism (p = 0.003). There were no statistically
significant differences between sexes. The Vulnerability to Abuse Screening Scale
acceptably evaluated validity in the transcultural adaptation process,
demonstrating dimensionality coherent with the original proposal (four factors).
In the internal consistency analysis, the instrument presented good results (KR
20 = 0.69) and the reliability via reproducibility was considered excellent for
the global scale (Kp = 0.92). CONCLUSIONS: The Vulnerability to Abuse Screening
Scale proved to be a valid instrument with good psychometric capacity for
screening domestic abuse against older adults in Brazil. OBJETIVO: Adaptar e
avaliar as propriedades psicometricas da Escala Triagem de Vulnerabilidade ao
Abuso (Vulnerability to Abuse Screening Scale - VASS) para identificar risco de
violencia domestica contra idosos no Brasil. METODOS: O instrumento foi adaptado
e validado em uma amostra de 151 idosos de um centro de referencia do idoso, do
municipio de Belo Horizonte, MG, em 2014. Foram coletadas informacoes
sociodemograficas, clinicas e relacionadas a abusos. A confiabilidade via
reprodutibilidade foi verificada em uma amostra de 55 idosos, submetidos ao
reteste do instrumento sete dias apos a primeira aplicacao. Foram realizadas
analises descritivas e comparativas para todas as variaveis, com nivel de
significancia de 5%. A validade de construto foi analisada pelo metodo de
componentes principais com matriz de correlacao tetracorica, a confiabilidade da
escala pela estatistica Kappa ponderado (Kp) e a consistencia interna pelo
estimador Kuder-Richardson formula 20 (KR-20). RESULTADOS: A idade media dos
participantes foi 72,1 anos (DP = 6,96; IC95% 70,94-73,17), com maxima de 92
anos, e o sexo foi predominantemente feminino (76,2%; IC95% 69,82-83,03). Ao
analisar a relacao entre os escores da Escala Triagem de Vulnerabilidade ao
Abuso, categorizados em presenca (indice > 3) ou ausencia (indice < 3) de
vulnerabilidade para abuso, com condicoes clinicas e de saude, encontramos
diferencas estatisticamente significantes para autopercepcao de saude (p =
0,002), sintomas depressivos (p = 0,000) e presenca de reumatismo (p = 0,003). Em
relacao ao sexo, nao houve diferenca estatisticamente significante. A Escala
Triagem de Vulnerabilidade ao Abuso comportou-se de forma aceitavel na avaliacao
da validade no processo de adaptacao transcultural, demonstrando dimensionalidade
coerente com a proposta original (quatro fatores). Na analise da consistencia
interna, o instrumento apresentou bons resultados (KR-20 = 0,69) e a
confiabilidade via reprodutibilidade foi considerara excelente para a escala
global (Kp = 0,92). CONCLUSOES: A Escala Triagem de Vulnerabilidade ao Abuso
mostra-se como instrumento valido e com boas capacidades psicometricas para o
rastreio de abuso domestico contra idosos no contexto brasileiro.
PMID- 28423138
TI - Intimate partner violence and maternal educational practice.
AB - OBJECTIVE: The objective of this study is to analyze the association between
intimate partner violence against women and maternal educational practice
directed to children at the beginning of formal education. METHODS: This is a
cross-sectional study, carried out between 2013 and 2014, with 631 mother/child
pairs, registered in the Family Health Strategy of the Health District II of the
city of Recife, State of Pernambuco, Brazil. It integrates a prospective cohort
study designed to investigate the consequences of exposure to intimate partner
violence in relation to the child who was born between 2005 and 2006. The
maternal educational practice has been assessed by the Parent-Child Conflict
Tactics Scale and the intimate partner violence by a questionnaire adapted from
the Multi-Country Study on Women's Health and Domestic Violence of the World
Health Organization. Intimate partner violence referred to the last 12 months and
was defined by specific acts of psychological, physical, and sexual violence
inflicted to women by the partner. The crude and adjusted prevalence ratios were
estimated for the association studied, using log-binomial regression. RESULTS:
The prevalence of intimate partner violence was 24.4%, and violent maternal
educational practice was 93.8%. The use of non-violent discipline was mentioned
by 97.6% of the women, coexisting with violent strategies of discipline. Children
whose mothers reported intimate partner violence presented a higher chance of
suffering psychological aggression (PR = 2.2; 95%CI 1.0-4.7). CONCLUSIONS: The
violence suffered by the mother interferes in the parental education. The
findings show high prevalence of violent maternal educational practice, pointing
to the need for interventions that minimize the damage of violence in women and
children. OBJETIVO: Analisar a associacao entre a violencia pelo parceiro intimo
contra a mulher e a pratica educativa materna direcionada as criancas no inicio
da escolaridade formal. METODOS: Estudo transversal, realizado entre 2013 e 2014,
com 631 pares mae/crianca, cadastradas na Estrategia de Saude da Familia do
Distrito Sanitario II da cidade do Recife, Pernambuco. Integra o estudo de coorte
prospectivo delineado para investigar as consequencias da exposicao a violencia
pelo parceiro intimo para a crianca que nasceu da gestacao que ocorreu entre 2005
e 2006. A pratica educativa materna foi avaliada pela escala de conflitos Parent
Child Conflict Tactics Scale e a violencia pelo parceiro intimo por um
questionario adaptado do Estudo Multipaises sobre a Saude da Mulher e Violencia
Domestica da Organizacao Mundial da Saude. A violencia pelo parceiro intimo
referiu-se aos ultimos 12 meses e foi definida por atos concretos de violencia
psicologica, fisica e sexual infligidos a mulher pelo parceiro. Foram estimadas
as razoes de prevalencia brutas e ajustadas para a associacao estudada,
utilizando-se a regressao log-binominal. RESULTADOS: A prevalencia da violencia
pelo parceiro intimo foi de 24,4%, e da pratica educativa materna violenta de
93,8%. O uso de disciplina nao violenta foi referido por 97,6% das mulheres,
coexistindo com estrategias violentas de disciplinamento. As criancas cujas maes
relataram violencia pelo parceiro intimo apresentaram maior chance de sofrer
agressao psicologica (RP = 2,2; IC95% 1,0-4,7). CONCLUSOES: A violencia sofrida
pela mae interfere na educacao parental. Os achados demonstram alta prevalencia
de pratica educativa materna que perpassa pela violencia, o que aponta para a
necessidade de intervencoes que minimizem os prejuizos da violencia na mulher e
na crianca.
PMID- 28423139
TI - Trend of leprosy in individuals under the age of 15 in Mato Grosso (Brazil), 2001
2013.
AB - OBJECTIVE: To identify the historical trend of leprosy epidemiological indicators
in individuals under the age of 15 in the state of Mato Grosso. METHODS:
Descriptive study with trend analysis of leprosy indicators in individuals under
the age of fifteen registered in the Mato Grosso's System for Notifiable Diseases
between 2001 and 2013. We used the Prais-Winsten procedure for analyzing
generalized linear regression at a significance level of 5%. We considered as
increasing time series when the annual percent change was positive, decreasing
when negative and stationary when there was no significant difference between its
value and zero. RESULTS: We analyzed 2455 cases of leprosy and the average
detection rate in individuals under the age of fifteen was 22.7 per 100 thousand
inhabitants. The trend of the general coefficient of incidence was decreasing,
with an average annual rate of -5.5% (95%CI -7.5--3.5). Increasing trend was
observed with an increase of 6.7% (95%CI 2.7-10.8) in the proportion of
multibacillary cases, 9.4% (95%CI 4.4-14.7) of cases diagnosed with dimorphic
clinical form and 14% (95%CI 7.9-20.4) of cases with physical disability level 2
at the time of diagnosis. There was an increasing trend in the average proportion
of examined contacts, with a growth of 4.1% (95%CI 1.2-7.1) and average
proportion of healing was precarious (39.7%), with stationary trend. CONCLUSIONS:
The historical trend of leprosy cases in individuals under the age of fifteen
proved to be decreasing in the period, however the trends of epidemiological
indicators such as the proportion of multibacillary cases, physical disability
level 2 and healing, indicate late diagnosis with stay sources of transmission
and consequent worsening of the disease in the state of Mato Grosso. OBJETIVO:
Identificar a tendencia historica dos indicadores epidemiologicos de hanseniase
em menores de 15 anos no estado de Mato Grosso. METODOS: Estudo descritivo com
analise de tendencia dos indicadores de hanseniase em menores de 15 anos
registrados no Sistema Nacional de Agravos de Notificacao de Mato Grosso, no
periodo de 2001 a 2013. Utilizou-se o procedimento de Prais-Winsten para analise
de regressao linear generalizada, adotando-se nivel de significancia de 5%.
Consideraram-se como serie temporal crescente quando a annual percent change era
positiva, decrescente quando negativa e estacionaria quando nao havia diferenca
significante entre seu valor e o zero. RESULTADOS: Foram analisados 2.455 casos
de hanseniase e o coeficiente medio de incidencia em menores de 15 anos foi de
22,7/100 mil habitantes. A tendencia geral do coeficiente de incidencia foi
decrescente, com uma annual percent change de -5,5% (IC95% -7,5-3,5). Observou-se
tendencia de crescimento, com incremento de 6,7% (IC95% 2,7-10,8) na proporcao
dos casos multibacilares, de 9,4% (IC95% 4,4-14,7) nos casos com forma clinica
dimorfa e de 14% (IC95% 7,9-20,4) nos casos com incapacidade fisica grau 2 no
momento do diagnostico da doenca. Verificou-se crescimento na proporcao dos
contatos de casos novos examinados, com incremento de 4,1% (IC95% 1,2-7,1) e
media da proporcao de cura considerada precaria (39,7%) com tendencia
estacionaria. CONCLUSOES: A tendencia historica dos casos de hanseniase em
menores de 15 anos mostrou-se decrescente no periodo. Entretanto, as tendencias
dos indicadores epidemiologicos, como a proporcao de casos multibacilares, de
incapacidade fisica grau 2 e de cura, indicam o diagnostico tardio com
permanencia de fontes de transmissibilidade e consequente agravo da endemia no
estado de Mato Grosso.
PMID- 28423140
TI - Arboviruses emerging in Brazil: challenges for clinic and implications for public
health.
AB - Arboviruses have been emerging in different parts of the world due to genetic
changes in the virus, alteration of the host and vector population dynamics, or
because of anthropogenic environmental factors. These viruses' capacity for
adaptation is notable, as well as the likelihood of their emergence and
establishment in new geographic areas. In Brazilian epidemiologic scenario, the
most common arboviruses are DENV, CHIKV, and ZIKV, although others may spread in
the country. Little is yet known of the impact of viral co-circulation, which
would theoretically result in more intense viremia or other immunological
alterations that could trigger autoimmune diseases, such as Guillain-Barre
syndrome. The impact on morbidity and mortality intensifies as extensive
epidemics lead to a high number of affected individuals, severe cases, and
implications for health services, mainly due to the absence of treatment,
vaccines, and effective prevention and control measures. RESUMO Notifica-se a
emergencia de arboviroses em diferentes regioes do planeta em decorrencia de
mudancas geneticas no virus, alteracao da dinamica populacional de hospedeiros e
vetores ou por fatores ambientais de origem antropogenica. E notavel a capacidade
de adaptacao desses virus e a possibilidade de emergirem e se estabelecerem em
novas areas geograficas. No contexto epidemiologico brasileiro, os arbovirus de
maior circulacao sao DENV, CHIKV e ZIKV, embora existam outros com potencial de
disseminacao no Pais. O impacto da cocirculacao viral ainda e pouco conhecido, a
qual teoricamente resultaria em viremias mais intensas ou outras alteracoes
imunologicas que poderiam ser o gatilho para doencas autoimunes, como a sindrome
de Guillain-Barre. O impacto na morbidade e mortalidade se intensifica a medida
que extensas epidemias pressupoem grande numero de individuos acometidos, casos
graves e implicacoes sobre os servicos de saude, principalmente diante da
ausencia de tratamento, vacinas e medidas efetivas de prevencao e controle.
PMID- 28423142
TI - Performing Percutaneous Coronary Intervention Without On-Site Cardiac Surgery Is
Not a License for Percutaneous Coronary Intervention Instead of Coronary Artery
Bypass Grafting-Reply.
PMID- 28423141
TI - Intimate partner violence and incidence of common mental disorder.
AB - OBJECTIVE: To investigate the association of intimate partner violence against
women reported in the last 12 months and seven years with the incidence of common
mental disorders. METHODS: A prospective cohort study with 390 women from 18 to
49 years, registered in the Family Health Program of the city of Recife, State of
Pernambuco; from July 2013 to December 2014. The Self Reporting Questionnaire-20
(SRQ-20) assessed mental health. Intimate partner violence consists of concrete
acts of psychological, physical or sexual violence that the partner inflicts on
the woman. Poisson regression was used to estimate crude and adjusted relative
risks (RR) of the association between common mental disorders and intimate
partner violence. RESULTS: The incidence of common mental disorders was 44.6%
among women who reported intimate partner violence in the last 12 months and
43.4% among those who reported in the past seven years. Mental disorders remained
associated with psychological violence (RR = 3.0; 95%CI 1.9-4.7 and RR = 1.8;
95%CI 1.0-3.7 in the last 12 months, and seven years, respectively), even in the
absence of physical or sexual violence. When psychological violence were related
to physical or sexual violence, the risk of common mental disorders was even
higher, both in the last 12 months (RR = 3.1; 95%CI 2.1-4.7) and in the last
seven years (RR = 2.5; 95%CI 1.7-3.8). CONCLUSIONS: Intimate partner violence is
associated with the incidence of common mental disorders in women. The treatment
of the consequences of IPV and support for women in seeking protection for
themselves for public services is essential. OBJETIVO: Investigar a associacao da
violencia por parceiros intimos relatada contra as mulheres nos ultimos 12 meses
e ultimos sete anos com a incidencia dos transtornos mentais comuns. METODOS:
Estudo de coorte prospectivo com 390 mulheres de 18 a 49 anos, cadastradas no
Programa Saude da Familia da cidade do Recife, PE, entre julho de 2013 e dezembro
de 2014. A saude mental foi avaliada pelo Self Reporting Questionnaire-20 (SRQ
20). A violencia por parceiro intimo foi definida por atos concretos de violencia
psicologica, fisica ou sexual infligidos a mulher pelo parceiro. A regressao de
Poisson foi utilizada para estimar os riscos relativos (RR) brutos e ajustados da
associacao entre transtorno mental comum e violencia por parceiro intimo.
RESULTADOS: A incidencia dos transtornos mentais comuns foi de 44,6% entre as
mulheres que relataram violencia nos ultimos 12 meses e de 43,4% nas que
relataram violencia nos ultimos sete anos. Os transtornos mentais mantiveram-se
associados a violencia psicologica (RR = 3,0; IC95% 1,9-4,7 e RR = 1,8; IC95% 1,0
3,7 nos ultimos 12 meses, e sete anos, respectivamente), mesmo na ausencia de
violencia fisica ou sexual. Quando a violencia psicologica esteve combinada com
violencia fisica ou sexual, o risco dos transtornos mentais comuns foi ainda mais
elevado, tanto nos ultimos 12 meses (RR = 3,1; IC95% 2,1-4,7) quanto nos ultimos
sete anos (RR = 2,5; IC95% 1,7-3,8). CONCLUSOES: A violencia por parceiro intimo
esta associada a incidencia de transtornos mentais comuns nas mulheres. E
fundamental o tratamento das consequencias da VPI e o apoio as mulheres na busca
de protecao para si pelos servicos publicos.
PMID- 28423143
TI - Leveraging the Benefits of Systemic Therapy to Tailor Surgery.
PMID- 28423144
TI - Efficacy of Catheter Ablation for Nonparoxysmal Atrial Fibrillation.
AB - Clinical Question: Is catheter ablation better than antiarrhythmic drugs for the
prevention of nonparoxysmal atrial fibrillation? Bottom Line: Radiofrequency
catheter ablation was found to be superior to antiarrhythmic drugs in preventing
recurrences of nonparoxysmal atrial fibrillation and reducing hospital
admissions.
PMID- 28423146
TI - Recovery in Patients With Dilated Cardiomyopathy With Loss-of-Function Mutations
in the Titin Gene.
PMID- 28423145
TI - Brief Behavioral Therapy for Pediatric Anxiety and Depression in Primary Care: A
Randomized Clinical Trial.
AB - Importance: Anxiety and depression affect 30% of youth but are markedly
undertreated compared with other mental disorders, especially in Hispanic
populations. Objective: To examine whether a pediatrics-based behavioral
intervention targeting anxiety and depression improves clinical outcome compared
with referral to outpatient community mental health care. Design, Setting, and
Participants: This 2-center randomized clinical trial with masked outcome
assessment conducted between brief behavioral therapy (BBT) and assisted referral
to care (ARC) studied 185 youths (aged 8.0-16.9 years) from 9 pediatric clinics
in San Diego, California, and Pittsburgh, Pennsylvania, recruited from October 6,
2010, through December 5, 2014. Youths who met DSM-IV criteria for full or
probable diagnoses of separation anxiety disorder, generalized anxiety disorder,
social phobia, major depression, dysthymic disorder, and/or minor depression;
lived with a consenting legal guardian for at least 6 months; and spoke English
were included in the study. Exclusions included receipt of alternate treatment
for anxiety or depression, presence of a suicidal plan, bipolar disorder,
psychosis, posttraumatic stress disorder, substance dependence, current abuse,
intellectual disability, or unstable serious physical illness. Interventions: The
BBT consisted of 8 to 12 weekly 45-minute sessions of behavioral therapy
delivered in pediatric clinics by master's-level clinicians. The ARC families
received personalized referrals to mental health care and check-in calls to
support accessing care from master's-level coordinators. Main Outcomes and
Measures: The primary outcome was clinically significant improvement on the
Clinical Global Impression-Improvement scale (score <=2). Secondary outcomes
included the Pediatric Anxiety Rating Scale, Children's Depression Rating Scale
Revised, and functioning. Results: A total of 185 patients were enrolled in the
study (mean [SD] age, 11.3 [2.6] years; 107 [57.8%] female; 144 [77.8%] white;
and 38 [20.7%] Hispanic). Youths in the BBT group (n = 95), compared with those
in the ARC group (n = 90), had significantly higher rates of clinical improvement
(56.8% vs 28.2%; chi21 = 13.09, P < .001; number needed to treat, 4), greater
reductions in symptoms (F2,146 = 5.72; P = .004; Cohen f = 0.28), and better
functioning (mean [SD], 68.5 [10.7] vs 61.9 [11.9]; t156 = 3.64; P < .001; Cohen
d = 0.58). Ethnicity moderated outcomes, with Hispanic youth having substantially
stronger response to BBT (76.5%) than ARC (7.1%) (chi21 = 14.90; P < .001; number
needed to treat, 2). Effects were robust across sites. Conclusions and Relevance:
A pediatric-based brief behavioral intervention for anxiety and depression is
associated with benefits superior to those of assisted referral to outpatient
mental health care. Effects were especially strong for Hispanic participants,
suggesting that the protocol may be a useful tool in addressing ethnic
disparities in care. Trial Registration: clinicaltrials.gov Identifier:
NCT01147614.
PMID- 28423148
TI - Increasing Resident Autonomy Without Compromising Patient Safety.
PMID- 28423147
TI - Adherence to High-Intensity Statins Following a Myocardial Infarction
Hospitalization Among Medicare Beneficiaries.
AB - Importance: High-intensity statins are recommended following myocardial
infarction. However, patients may not continue taking this medication with high
adherence. Objective: To estimate the proportion of patients filling high
intensity statin prescriptions following myocardial infarction who continue
taking this medication with high adherence and to analyze factors associated with
continuing a high-intensity statin with high adherence after myocardial
infarction. Design, Setting, and Participants: Retrospective cohort study of
Medicare patients following hospitalization for myocardial infarction. Medicare
beneficiaries aged 66 to 75 years (n = 29 932) and older than 75 years (n = 27
956) hospitalized for myocardial infarction between 2007 and 2012 who filled a
high-intensity statin prescription (atorvastatin, 40-80 mg, and rosuvastatin, 20
40 mg) within 30 days of discharge. Beneficiaries had Medicare fee-for-service
coverage including pharmacy benefits. Exposures: Sociodemographic, dual
Medicare/Medicaid coverage, comorbidities, not filling high-intensity statin
prescriptions before their myocardial infarction (ie, new users), and cardiac
rehabilitation and outpatient cardiologist visits after discharge. Main Outcomes
and Measures: High adherence to high-intensity statins at 6 months and 2 years
after discharge was defined by a proportion of days covered of at least 80%, down
titration was defined by switching to a low/moderate-intensity statin with a
proportion of days covered of at least 80%, and low adherence was defined by a
proportion of days covered less than 80% for any statin intensity without
discontinuation. Discontinuation was defined by not having a statin available to
take in the last 60 days of each follow-up period. Results: Approximately half of
the beneficiaries were women and fourth-fifths were white. At 6 months and 2
years after discharge among beneficiaries 66 to 75 years of age, 17 633 (58.9%)
and 10 308 (41.6%) were taking high-intensity statins with high adherence, 2605
(8.7%) and 3315 (13.4%) down-titrated, 5182 (17.3%) and 4727 (19.1%) had low
adherence, and 3705 (12.4%) and 4648 (18.8%) discontinued their statin,
respectively. The proportion taking high-intensity statins with high adherence
increased between 2007 and 2012. African American patients, Hispanic patients,
and new high-intensity statin users were less likely to take high-intensity
statins with high adherence, and those with dual Medicare/Medicaid coverage and
more cardiologist visits after discharge and who participated in cardiac
rehabilitation were more likely to take high-intensity statins with high
adherence. Results were similar among beneficiaries older than 75 years of age.
Conclusions and Relevance: Many patients filling high-intensity statins following
a myocardial infarction do not continue taking this medication with high
adherence for 2 years postdischarge. Interventions are needed to increase high
intensity statin use and adherence after myocardial infarction.
PMID- 28423149
TI - Transdiagnostic Behavioral Therapies in Pediatric Primary Care: Looking Ahead.
PMID- 28423150
TI - Typographical Errors and Missing Table Footnote.
PMID- 28423151
TI - Diversity in Dermatology-A Call for Action.
PMID- 28423152
TI - Multiple Facial Trichoepitheliomas and Vulval Cysts: Extending the Phenotypic
Spectrum in CYLD Cutaneous Syndrome.
PMID- 28423153
TI - Heterogeneity in Blood Pressure Transitions Over the Life Course: Age-Specific
Emergence of Racial/Ethnic and Sex Disparities in the United States.
AB - Importance: Many studies have assessed racial/ethnic and sex disparities in the
prevalence of elevated blood pressure (BP) from childhood to adulthood, yet few
have examined differences in age-specific transitions between categories of BP
over the life course in contemporary, multiracial/multiethnic populations.
Objective: To estimate age, racial/ethnic, and sex-specific annual net transition
probabilities between categories of BP using Markov modeling of cross-sectional
data from the National Health and Nutrition Examination Survey. Design, Setting,
and Participants: National probability sample (National Health and Nutrition
Examination Survey in 2007-2008, 2009-2010, and 2011-2012) of 17 747 African
American, white American, and Mexican American participants aged 8 to 80 years.
The data were analyzed from September 2014 to November 2015. Main Outcomes and
Measures: Age-specific American Heart Association-defined BP categories. Results:
Three National Health and Nutrition Examination Survey cross-sectional samples
were used to characterize the ages at which self-reported African American (n =
4973), white American (n = 8886), and Mexican American (n = 3888) populations
transitioned between ideal BP, prehypertension, and hypertension across the life
course. At age 8 years, disparities in the prevalence of ideal BP were observed,
with the prevalence being lower among boys (86.6%-88.8%) compared with girls
(93.0%-96.3%). From ages 8 to 30 years, annual net transition probabilities from
ideal to prehypertension among male individuals were more than 2 times the net
transition probabilities of their female counterparts. The largest net transition
probabilities for ages 8 to 30 years occurred in African American young men,
among whom a net 2.9% (95% CI, 2.3%-3.4%) of those with ideal BP transitioned to
prehypertension 1 year later. Mexican American young women aged 8 to 30 years
experienced the lowest ideal to prehypertension net transition probabilities
(0.6%; 95% CI, 0.3%-0.8%). After age 40 years, ideal to prehypertension net
transition probabilities stabilized or decreased (range, 3.0%-4.5%) for men,
whereas net transition probabilities for women increased rapidly (range, 2.6%
13.0%). Mexican American women exhibited the largest ideal to prehypertension net
transition probabilities after age 60 years. The largest prehypertension to
hypertension net transition probabilities occurred at young ages in boys of white
race/ethnicity and African Americans, approximately age 8 years and age 25 years,
respectively, while net transition probabilities for white women and Mexican
Americans increased over the life course. Conclusions and Relevance:
Heterogeneity in net transition probabilities from ideal BP emerge during
childhood, with associated rapid declines in ideal BP observed in boys and
African Americans, thus introducing disparities. Primordial prevention beginning
in childhood and into early adulthood is necessary to preempt the development of
prehypertension and hypertension, as well as associated racial/ethnic and sex
disparities.
PMID- 28423155
TI - The Role of Genetic Testing in Patients With Breast Cancer: A Review.
AB - Importance: In the United States from 2009 to 2013, the incidence of breast
cancer was the highest of any cancer and the death rate was second to that of
lung cancer. Approximately 5% to 10% of breast cancers are inheritable.
Observations: BRCA1 and BRCA2 germline mutations account for up to 30% of
inheritable breast cancers and are the most commonly assessed mutations in
patients presenting with early-onset breast cancer, triple-negative breast
cancer, bilateral breast cancer, and a family history of breast cancer. Less
common non-BRCA mutations have also been identified and contribute to hereditary
breast cancer syndromes. Although established in BRCA mutations, indications and
interpretations of genetic testing in non-BRCA mutations are not well defined.
Furthermore, costs associated with genetic testing are highly variable and
dependent on laboratory pricing, insurance coverage, and individual risk factors.
Conclusions and Relevance: Genetic testing is a powerful tool that allows for the
detection of BRCA and non-BRCA germline mutations in individuals with high risks
of breast cancer, which in turn aids in the individualization of treatment. Given
the magnitude of this disease, it is of great benefit for physicians, including
general surgeons, to understand the indications, interpretations, and costs
associated with genetic testing in patients with breast cancer. Cost is an
especially important part of the genetic testing process and point of discussion
with patients.
PMID- 28423154
TI - Association of Mental Disorders and Related Medication Use With Risk for Major
Osteoporotic Fractures.
AB - Importance: Osteoporotic fractures are a leading cause of disability, costs, and
mortality. FRAX is a tool used to assess fracture risk in the general population.
Mental disorders and medications to treat them have been reported to adversely
affect bone health, but, to date, they have not been systematically studied in
relation to osteoporotic fractures. Objective: To examine the association of
mental disorders and psychotropic medication use with osteoporotic fracture risk
in routine clinical practice. Design, Setting, and Participants: In this
population-based cohort study, bone mineral density and risk factors were used to
calculate FRAX scores using data from the Manitoba Bone Density Program database
of all women and men 40 years of age or older in Manitoba, Canada, referred for a
baseline dual-energy x-ray absorptiometry scan from January 1, 1996, to March 28,
2013. Population-based health services data were used to identify primary mental
disorders during the 3 prior years, psychotropic medication use during the prior
year, and incident fractures. Cox proportional hazards regression models
estimated the risk for incident fractures based on mental disorders and use of
psychotropic medications. Data analysis was conducted from November 25, 2013, to
October 15, 2016. Main Outcomes and Measures: Incident nontraumatic major
osteoporotic fractures (MOFs) and hip fractures. Results: Of the 68 730
individuals (62 275 women and 6455 men; mean age, 64.2 [11.2] years) in the
study, during 485 322 person-years (median, 6.7 years) of observation, 5750
(8.4%) sustained an incident MOF, 1579 (2.3%) sustained an incident hip fracture,
and 8998 (13.1%) died. In analyses adjusted for FRAX score, depression was
associated with MOF (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.27-1.51; P <
.05) and hip fracture (aHR, 1.43; 95% CI, 1.22-1.69; P < .05) before adjustment
for medication use, but these associations were not significant after adjustment
for medication use. In contrast, the use of selective serotonin reuptake
inhibitors (aHR for MOF, 1.43; 95% CI, 1.27-1.60; P < .05; aHR for hip fracture,
1.48; 95% CI, 1.18-1.85; P < .05), antipsychotics (aHR for MOF, 1.43; 95% CI,
1.15-1.77; P < .05; aHR for hip fracture, 2.14; 95% CI, 1.52-3.02; P < .05), and
benzodiazepines (aHR for MOF, 1.15; 95% CI, 1.04-1.26; P < .05; aHR for hip
fracture, 1.24; 95% CI, 1.05-1.47; P < .05) were each independently associated
with significantly increased risk for both MOF and hip fracture. FRAX
significantly underestimated the 10-year risk of MOF by 29% and of hip fracture
by 51% for those with depression. It also underestimated the 10-year risk of MOF
by 36% for use of selective serotonin reuptake inhibitors, by 63% for use of mood
stabilizers, by 60% for use of antipsychotics, and by 13% for use of
benzodiazepines. FRAX underestimated the 10-year risk of hip fracture by 57% for
use of selective serotonin reuptake inhibitors, by 98% for use of mood
stabilizers, by 171% for use of antipsychotics, and by 31% for use of
benzodiazepines. FRAX correctly estimated fracture risk in people without mental
disorders and those not taking psychotropic medications. Conclusions and
Relevance: Mental disorders and medication use were associated with an increased
risk for fracture, but in simultaneous analyses, only medication use was
independently associated with fracture. Depression and psychotropic medication
use are potential risk indicators that are independent of FRAX estimates.
PMID- 28423156
TI - Creation of an Internal Teledermatology Store-and-Forward System in an Existing
Electronic Health Record: A Pilot Study in a Safety-Net Public Health and
Hospital System.
AB - Importance: External store-and-forward (SAF) teledermatology systems operate
separately from the primary health record and have many limitations, including
care fragmentation, inadequate communication among clinicians, and privacy and
security concerns, among others. Development of internal SAF workflows within
existing electronic health records (EHRs) should be the standard for large health
care organizations for delivering high-quality dermatologic care, improving
access, and capturing other telemedicine benchmark data. Epic EHR software (Epic
Systems Corporation) is currently one of the most widely used EHR system in the
United States, and development of a successful SAF workflow within it is needed.
Objectives: To develop an SAF teledermatology workflow within the Epic system,
the existing EHR system of Parkland Health and Hospital System (Dallas, Texas),
assess its effectiveness in improving access to care, and validate its
reliability; and to evaluate the system's ability to capture meaningful outcomes.
Design, Setting, and Participants: Electronic consults were independently
evaluated by 2 board-certified dermatologists, who provided diagnoses and
treatment plans to primary care physicians (PCPs). Results were compared with in
person referrals from May to December 2013 from the same clinic (a community
outpatient clinic in a safety-net public hospital system). Patients were those 18
years or older with dermatologic complaints who would have otherwise been
referred to dermatology clinic. Main Outcomes and Measures: Median time to
evaluation; percentage of patients evaluated by a dermatologist through either
teledermatology or in-person compared with the previous year. Results: Seventy
nine teledermatology consults were placed by 6 PCPs from an outpatient clinic
between May and December 2014; 57 (74%) were female and their mean (SD) age was
47.0 (12.4) years. Teledermatology reduced median time to evaluation from 70.0
days (interquartile range [IQR], 33.25-83.0 days) to 0.5 days (IQR, 0.172-0.94
days) and median time to treatment from 73.5 to 3.0 days compared with in-person
dermatology visits. Overall, a greater percentage of patients (120 of 144
[83.3%]) were evaluated by a dermatologist through either teledermatology or in
person during the 2014 study period compared with the previous year (111 of 173
[64.2%]). Primary care physicians followed management recommendations 93% of the
time. Conclusions and Relevance: Epic-based SAF teledermatology can improve
access to dermatologic care in a public safety-net hospital setting. We hope that
the system will serve as a model for other health care organizations wanting to
create SAF teledermatology workflows within the Epic EHR system.
PMID- 28423157
TI - Hypertension Disparities: The Hidden Vulnerability of Youth.
PMID- 28423158
TI - Declining Melanoma Rates in New England States.
PMID- 28423159
TI - Performing Percutaneous Coronary Intervention Without On-site Cardiac Surgery Is
Not a License for Percutaneous Coronary Intervention Instead of Coronary Artery
Bypass Grafting.
PMID- 28423160
TI - Sex First-A New View of the Origins of Eukaryotes.
PMID- 28423161
TI - An Unusual Case of Syringocystadenocarcinoma Papilliferum In Situ With Macular
Amyloidosis.
PMID- 28423162
TI - A Pilot Use of Patient-Generated Wound Data to Improve Postdischarge Surgical
Site Infection Monitoring.
PMID- 28423163
TI - Metafrontier frameworks for studying hospital productivity growth and quality
changes.
AB - Objective: The objective of this study was to evaluate productivity growth and
quality changes among different levels of accredited hospitals. Design: This
study used an attribute-incorporating Malmquist productivity index (MPI) under
the metafrontier framework. This is the first attempt to compare productivity
changes among hospitals operating under different production frontiers.
Participants: The data consisted of 20 academic medical centers (AMCs), 61
metropolitan hospitals (MPs) and 112 local community hospitals (LCs) in Taiwan
during the period 2007-2010. Main outcome measures: This study measured
productivity growth and further identified technological gaps and catch-ups in
different groups of hospitals with respect to the metafrontier. At the same time,
comparisons of changes in quality among different levels of hospitals were also
examined. Results: We found that the sample hospitals of AMCs and MPs experienced
productivity improvements mainly due to technological progress, but their
efficiency and technology gap ratio (TGR) deteriorated. As for LCs, progress in
technology along with improvements in their efficiency and TGR led to the highest
productivity upgrade among the three groups of hospitals. We also found that the
sample hospitals among the three groups showed improvements in quality. Moreover,
hospitals in the local community group exhibited greater quality progress than
the AMCs and MPs over the sample period. Conclusion: This paper presents a number
of useful decompositions of the metafrontier MPI, which can provide useful
insights into changes that are due to efficiency, quality improvements and/or
technological changes in the healthcare sector.
PMID- 28423164
TI - Triple Aim in Canada: developing capacity to lead to better health, care and
cost.
AB - Quality problem: Many modern health systems strive for 'Triple Aim' (TA)-better
health for populations, improved experience of care for patients and lower costs
of the system, but note challenges in implementation. Outcomes of applying TA as
a quality improvement framework (QI) have started to be realized with early
lessons as to why some systems make progress while others do not. Initial
assessment: Limited evidence is available as to how organizations create the
capacity and infrastructure required to design, implement, evaluate and sustain
TA systems. Choice of solution: To support embedding TA across Canada, the
Canadian Foundation for Healthcare Improvement supported enrolment of nine
Canadian teams to participate in the Institute for Healthcare Improvement's TA
Improvement Community. Implementation: Structured support for TA design,
implementation, evaluation and sustainability was addressed in a collaborative
programme of webinars and action periods. Teams were coached to undertake and
test small-scale improvements before attempting to scale. Evaluation: A summative
evaluation of the Canadian cohort was undertaken to assess site progress in
building TA infrastructure across various healthcare settings. The evaluation
explored the process of change, experiences and challenges and strategies for
continuous QI. Lessons learned: Delivering TA requires a sustained and
coordinated effort supported by strong leadership and governance, continuous QI,
engaged interdisciplinary teams and partnering within and beyond the healthcare
sector.
PMID- 28423165
TI - A randomized comparison between league tables and funnel plots to inform health
care decision-making.
AB - Objective: Comparison of provider performance is commonly used to inform health
care decision-making. Little attention has been paid to how data presentations
influence decisions. This study analyzes differences in suggested actions by
decision-makers informed by league tables or funnel plots. Design: Decision
makers were invited to a survey and randomized to compare hospital performance
using either league tables or funnel plots for four different measures within the
area of cancer care. For each measure, decision-makers were asked to suggest
actions towards 12-16 hospitals (no action, ask for more information, intervene)
and provide feedback related to whether the information provided had been useful.
Setting: Swedish health care. Participants: Two hundred and twenty-one decision
makers at administrative and clinical levels. Intervention: Data presentations in
the form of league tables or funnel plots. Main outcome measures: Number of
actions suggested by participants. Proportion of appropriate actions. Results:
For all four measures, decision-makers tended to suggest more actions based on
the information provided in league tables compared to funnel plots (44% vs. 21%,
P < 0.001). Actions were on average more appropriate for funnel plots. However,
when using funnel plots, decision-makers more often missed to react even when
appropriate. Conclusions: The form of data presentation had an influence on
decision-making. With league tables, decision-makers tended to suggest more
actions compared to funnel plots. A difference in sensitivity and specificity
conditioned by the form of presentation could also be identified, with different
implications depending on the purpose of comparisons. Explanations and
visualization aids are needed to support appropriate actions.
PMID- 28423166
TI - Leonine Facies, Flushing, and Systemic Symptoms.
PMID- 28423167
TI - What pre-Columbian mummies could teach us about South American leishmaniases?
AB - A recent report on the taxonomic profile of the human gut microbiome in pre
Columbian mummies (Santiago-Rodriguez et al. 2016) gives for the first time
evidence of the presence of Leishmania DNA (sequences similar to Leishmania
donovani according to the authors) that can be reminiscent of visceral
leishmaniasis during the pre-Columbian era. It is commonly assumed that
Leishmania infantum, the etiological agent of American visceral leishmaniasis
(AVL) was introduced into the New World by the Iberian conquest. This finding is
really surprising and must be put into perspective with what is known from an AVL
epidemiological and historical point of view. Beside L. infantum, there are other
species that are occasionally reported to cause AVL in the New World. Among
these, L. colombiensis is present in the region of pre-Columbian mummies studied.
Other explanations for these findings include a more ancient introduction of a
visceral species of Leishmania from the Old World or the existence of a yet
unidentified endemic species causing visceral leishmaniasis in South America.
Unfortunately, very few molecular data are known about this very long pre
Columbian period concerning the circulating species of Leishmania and their
diversity in America.
PMID- 28423168
TI - The significance of Candida in the human respiratory tract: our evolving
understanding.
AB - Candida is an opportunistic pathogen and the most commonly isolated fungal genus
in humans. Though Candida is often detected in respiratory specimens from humans
with and without lung disease, its significance remains undetermined. While
historically considered a commensal organism with low virulence potential, the
status of Candida as an innocent bystander has recently been called into question
by both clinical observations and animal experimentation. We here review what is
currently known and yet to be determined about the clinical, microbiological and
pathophysiological significance of the detection of Candida spp. in the human
respiratory tract.
PMID- 28423169
TI - Innate immune response to lipooligosaccharide: pivotal regulator of the
pathobiology of invasive Neisseria meningitidis infections.
AB - Infections due to Neisseria meningitidis afflict more than one million people
worldwide annually and cause death or disability in many survivors. The clinical
course of invasive infections has been well studied, but our understanding of the
cause of differences in patient outcomes has been limited because these are
dependent on multiple factors including the response of the host, characteristics
of the bacteria and interactions between the host and the bacteria. The
meningococcus is a highly inflammatory organism, and the lipooligosaccharide
(LOS) on the outer membrane is the most potent inflammatory molecule it expresses
due to the interactions of the lipid A moiety of LOS with receptors of the innate
immune system. We previously reported that increased phosphorylation of
hexaacylated neisserial lipid A is correlated with greater inflammatory
potential. Here we postulate that variability in lipid A phosphorylation can tip
the balance of innate immune responses towards homeostatic tolerance or
proinflammatory signaling that affects adaptive immune responses, causing disease
with meningitis only, or septicemia with or without meningitis, respectively.
Furthermore, we propose that studies of the relationship between bacterial
virulence and gene expression should consider whether genetic variation could
affect properties of biosynthetic enzymes resulting in LOS structural differences
that alter disease pathobiology.
PMID- 28423170
TI - US Emergency Department Encounters for Law Enforcement-Associated Injury, 2006
2012.
PMID- 28423171
TI - Identification of Patients With Documented Pathologic Complete Response in the
Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery.
AB - Importance: A pathologic complete response (pCR; no invasive or in situ cancer)
occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative
(TN) breast cancer. The need for surgery if percutaneous biopsy of the breast
after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter
referred to as breast pCR) has been questioned, and appropriate management of the
axilla in such patients is unknown. Objective: To identify patients among
exceptional responders to NCT with a low risk for axillary metastases when breast
pCR is documented who may be eligible for an omission of surgery clinical trial
design. Design, Setting, and Participants: This prospective cohort study at a
single-institution academic national comprehensive cancer center included 527
consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT
followed by standard breast and nodal surgery from January 1, 2010, through
December 31, 2014. Main Outcomes and Measures: Patients who achieved a breast pCR
were compared with patients who did not based on subtype, initial
ultrasonographic findings, and documented pathologic nodal status. Incidence of
positive findings for nodal disease on final pathologic review was calculated for
patients with and without pCR and compared using relative risk ratios with 95%
CIs. Results: The analysis included 527 patients (median age, 51 [range, 23-84]
years). Among 290 patients with initial nodal ultrasonography showing N0 disease,
116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node
metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease,
69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence
of residual nodal disease (P < .01). Patients without a breast pCR had a relative
risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P < .001) compared
with those with a breast pCR. Conclusions and Relevance: Breast pCR is highly
correlated with nodal status after NCT, and the risk for missing nodal metastases
without axillary surgery in this cohort is extremely low. These data provide the
fundamental basis and rationale for management of the axilla in clinical trials
of omission of cancer surgery when image-guided biopsy indicates a breast pCR.
PMID- 28423174
TI - Comparison of Efficacy and Safety Between Propranolol and Steroid for Infantile
Hemangioma: A Randomized Clinical Trial.
AB - Importance: There are limited data from randomized clinical trials comparing
propranolol and steroid medication for treatment of infantile hemangioma (IH).
Objective: To determine the efficacy and safety of propranolol compared with
steroid as a first-line treatment for IH. Design, Setting, and Participants: This
randomized clinical noninferiority trial tested the efficacy and safety of
propranolol vs steroid treatment for IH at a single academic hospital. All
participants were diagnosed with IH between June 2013 and October 2014, had
normal heart function, and had not been previously treated for IH. Interventions:
The participants were randomly assigned to either the propranolol group or the
steroid group. In the propranolol group, the patients were admitted, observed for
adverse effects for 3 days after treatment initiation, and then released and
treated as outpatients for 16 weeks (2 mg/kg/d). In the steroid group, the
patients were seen as outpatients from the beginning and were also treated for 16
weeks (2 mg/kg/d). Main Outcomes and Measures: The primary efficacy variable was
the response to treatment at 16 weeks, which was evaluated by the hemangioma
volume using magnetic resonance imaging before and at 16 weeks after treatment
initiation. While comparing the effect of medication between the groups, we
monitored the adverse effects of both drugs. Results: A total of 34 patients (15
boys, 19 girls; mean age, 3.3 months; range, 0.3-8.2 months) were randomized to
receive either propranolol or steroid treatment (17 in each treatment group).
Guardians for 2 patients in the steroid group withdrew their consent, and 1
patient in the propranolol group did not complete the efficacy test. The
intention-to-treat analysis, applying multiple imputations, found the treatment
response rate in the propranolol group to be 95.65%, and that of the steroid
group was 91.94%. Because the difference in response rate between the groups was
3.71%, propranolol was considered noninferior. We found that there was no
difference between the groups in safety outcomes. Conclusions and Relevance: Our
trial demonstrated that propranolol was not inferior to steroid with respect to
therapeutic effects in IH. Trial Registration: clinicaltrials.gov Identifier:
NCT01908972.
PMID- 28423177
TI - Comparison of Appendectomy Outcomes Between Senior General Surgeons and General
Surgery Residents.
AB - Importance: In some centers, the presence of a senior general surgeon (SGS) is
obligatory in every procedure, including appendectomy, while in others it is not.
There is a relative paucity in the literature of reports comparing the outcomes
of appendectomies performed by unsupervised general surgery residents (GSRs) with
those performed in the presence of an SGS. Objective: To compare the outcomes of
appendectomies performed by SGSs with those performed by GSRs. Design, Setting,
and Participants: A retrospective analysis was performed of all patients 16 years
or older operated on for assumed acute appendicitis between January 1, 2008, and
December 31, 2015. The cohort study compared appendectomies performed by SGSs and
GSRs in the general surgical department of a teaching hospital. Main Outcomes and
Measures: The primary outcome measured was the postoperative early and late
complication rates. Secondary outcomes included time from emergency department to
operating room, length of surgery, surgical technique (open or laparoscopic), use
of laparoscopic staplers, and overall duration of postoperative antibiotic
treatment. Results: Among 1649 appendectomy procedures (mean [SD] patient age,
33.7 [13.3] years; 612 female [37.1%]), 1101 were performed by SGSs and 548 by
GSRs. Analysis demonstrated no significant difference between the SGS group and
the GSR group in overall postoperative early and late complication rates, the use
of imaging techniques, time from emergency department to operating room,
percentage of complicated appendicitis, postoperative length of hospital stay,
and overall duration of postoperative antibiotic treatment. However, length of
surgery was significantly shorter in the SGS group than in the GSR group (mean
[SD], 39.9 [20.9] vs 48.6 [20.2] minutes; P < .001). Conclusions and Relevance:
This study demonstrates that unsupervised surgical residents may safely perform
appendectomies, with no difference in postoperative early and late complication
rates compared with those performed in the presence of an SGS.
PMID- 28423179
TI - Glucan synthase-like 2 is indispensable for paramylon synthesis in Euglena
gracilis.
AB - The phytoflagellate Euglena gracilis produces a large amount of paramylon (PM), a
conglomerate of liner beta-1,3-glucan chains, as a storage polysaccharide. PM is
synthesized from uridine diphosphate-glucose, but its mechanism of formation is
largely unknown. Two enzymes, glucan synthase-like (EgGSL) 1 and EgGSL2 were
previously identified as candidates for PM synthesis in a Euglena transcriptome
analysis. Here, we performed a reverse genetic analysis on these enzymes.
Knockdown of EgGSL2, but not EgGSL1, significantly inhibits PM accumulation in
Euglena cells. Additionally, beta-1,3-glucan synthesis is detected in a PM
associated membrane fraction extracted from Euglena cells. Our findings indicate
that EgGSL2 is the predominant enzyme for PM biosynthesis.
PMID- 28423180
TI - MiR-19 regulates breast cancer cell aggressiveness by targeting profilin 1.
PMID- 28423178
TI - Head-to-head comparison of structurally unrelated dipeptidyl peptidase 4
inhibitors in the setting of renal ischemia reperfusion injury.
AB - BACKGROUND AND PURPOSE: Results regarding protective effects of dipeptidyl
peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are
conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a
model of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized
male rats by renal artery clamping for 30 min. The sham group was
uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given
p.o. once daily on three consecutive days prior to IRI: linagliptin (1.5 mg.kg-1
.day-1 ), vildagliptin (8 mg.kg-1 .day-1 ) and sitagliptin (30 mg.kg-1 .day-1 ).
An additional group received sitagliptin until study end (before IRI: 30 mg.kg-1
.day-1 ; after IRI: 15 mg.kg-1 .day-1 ). KEY RESULTS: Plasma-active glucagon-like
peptide type 1 (GLP-1) increased threefold to fourfold in all DPP4 inhibitor
groups 24 h after IRI. Plasma cystatin C, a marker of GFR, peaked 48 h after IRI.
Compared with the placebo group, DPP4 inhibition did not reduce increased plasma
cystatin C levels. DPP4 inhibitors ameliorated histopathologically assessed
tubular damage with varying degrees of drug-specific efficacies. Renal
osteopontin expression was uniformly reduced by all DPP4 inhibitors. IRI-related
increased renal cytokine expression was not decreased by DPP4 inhibition. Renal
DPP4 activity at study end was significantly inhibited in the linagliptin group,
but only numerically reduced in the prolonged/dose-adjusted sitagliptin group.
Active GLP-1 plasma levels at study end were increased only in the prolonged/dose
adjusted sitagliptin treatment group. CONCLUSIONS AND IMPLICATIONS: In rats with
renal IRI, DPP4 inhibition did not alter plasma cystatin C, a marker of
glomerular function, but may protect against tubular damage.
PMID- 28423181
TI - Mesenteric lymph node CD11b- CD103+ PD-L1High dendritic cells highly induce
regulatory T cells.
AB - Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3+ regulatory T
cells to regulate immune responses to beneficial or non-harmful agents in the
intestine, such as commensal bacteria and foods. Several studies in MLN DCs have
revealed that the CD103+ DC subset highly induces regulatory T cells, and another
study has reported that MLN DCs from programmed death ligand 1 (PD-L1) -deficient
mice could not induce regulatory T cells. Hence, the present study investigated
the expression of these molecules on MLN CD11c+ cells. Four distinct subsets
expressing CD103 and/or PD-L1 were identified, namely CD11b+ CD103+ PD-L1High ,
CD11b- CD103+ PD-L1High , CD11b- CD103+ PD-L1Low and CD11b+ CD103- PD-L1Int .
Among them, the CD11b- CD103+ PD-L1High DC subset highly induced Foxp3+ T cells.
This subset expressed Aldh1a2 and Itgb8 genes, which are involved in retinoic
acid metabolism and transforming growth factor-beta (TGF-beta) activation,
respectively. Exogenous TGF-beta supplementation equalized the level of Foxp3+ T
cell induction by the four subsets whereas retinoic acid did not, which suggests
that high ability to activate TGF-beta is determinant for the high Foxp3+ T-cell
induction by CD11b- CD103+ PD-L1High DC subset. Finally, this subset exhibited a
migratory DC phenotype and could take up and present orally administered
antigens. Collectively, the MLN CD11b- CD103+ PD-L1High DC subset probably takes
up luminal antigens in the intestine, migrates to MLNs, and highly induces
regulatory T cells through TGF-beta activation.
PMID- 28423183
TI - Long-term species loss and homogenization of moth communities in Central Europe.
AB - As global biodiversity continues to decline steeply, it is becoming increasingly
important to understand diversity patterns at local and regional scales. Changes
in land use and climate, nitrogen deposition and invasive species are the most
important threats to global biodiversity. Because land use changes tend to
benefit a few species but impede many, the expected outcome is generally
decreasing population sizes, decreasing species richness at local and regional
scales, and increasing similarity of species compositions across sites (biotic
homogenization). Homogenization can be also driven by invasive species or effects
of soil eutrophication propagating to higher trophic levels. In contrast, in the
absence of increasing aridity, climate warming is predicted to generally increase
abundances and species richness of poikilotherms at local and regional scales. We
tested these predictions with data from one of the few existing monitoring
programmes on biodiversity in the world dating to the 1960s, where the abundance
of 878 species of macro-moths have been measured daily at seven sites across
Hungary. Our analyses revealed a dramatic rate of regional species loss and
homogenization of community compositions across sites. Species with restricted
distribution range, specialized diet or dry grassland habitat were more likely
than others to disappear from the community. In global context, the contrasting
effects of climate change and land use changes could explain why the predicted
enriching effects from climate warming are not always realized.
PMID- 28423182
TI - Crystal structure of the EnvZ periplasmic domain with CHAPS.
AB - Bacteria sense and respond to osmolarity through the EnvZ-OmpR two-component
system. The structure of the periplasmic sensor domain of EnvZ (EnvZ-PD) is not
available yet. Here, we present the crystal structure of EnvZ-PD in the presence
of CHAPS detergent. The structure of EnvZ-PD shows similar folding topology to
the PDC domains of PhoQ, DcuS, and CitA, but distinct orientations of helices and
beta-hairpin structures. The CD and NMR spectra of EnvZ-PD in the presence of
cholate, a major component of bile salts, are similar to those with CHAPS.
Chemical cross-linking shows that the dimerization of EnvZ-PD is significantly
inhibited by the CHAPS and cholate. Together with beta-galactosidase assay, these
results suggest that bile salts may affect the EnvZ structure and function in
Escherichia coli.
PMID- 28423184
TI - The differentiated and conserved roles of Swi5-Sfr1 in homologous recombination.
AB - Homologous recombination (HR) is the process whereby two DNA molecules that share
high sequence similarity are able to recombine to generate hybrid DNA molecules.
Throughout evolution, the ability of HR to identify highly similar DNA sequences
has been adopted for numerous biological phenomena including DNA repair, meiosis,
telomere maintenance, ribosomal DNA amplification and immunological diversity.
Although Rad51 and Dmc1 are the key proteins that promote HR in mitotic and
meiotic cells, respectively, accessory proteins that allow Rad51 and Dmc1 to
effectively fulfil their functions have been identified in all examined model
systems. In this Review, we discuss the roles of the highly conserved Swi5-Sfr1
accessory complex in yeast, mice and humans, and explore similarities and
differences between these species.
PMID- 28423186
TI - The dynamics of searching for meaning and presence of meaning in daily life.
AB - OBJECTIVE: Research on searching for meaning in life has focused on trait-level
relationships rather than within-person relationships. Our goal was to examine
within-person relationships between daily states of searching for meaning in
life, daily states of presence of meaning in life, and daily states of well
being. METHOD: To advance our understanding of searching for meaning in life, we
conducted a daily diary study with two samples in which 254 undergraduate
students (Mage = 18.54, SD = 1.55; 66.9% female) completed daily reports of
presence and search for meaning in life and well-being for 2 weeks (n = 3,288).
RESULTS: Between persons, search was negatively related to presence and well
being. In contrast, within persons, daily search was positively related to
presence and well-being. Relationships between daily search and daily well-being
were mediated by daily presence of meaning in life. Lagged analyses indicated
that greater search on one day led to greater presence the next day. CONCLUSIONS:
The implications of these within-person findings suggest that researchers should
reconsider the potential consequences that occur from searching for meaning in
life, including the possibility that greater searching is associated with
increased well-being.
PMID- 28423187
TI - Characterization of the binding capacity of mercurial species in Lactobacillus
strains.
AB - BACKGROUND: Metal sequestration by bacteria has been proposed as a strategy to
counteract metal contamination in foodstuffs. Lactobacilli can interact with
metals, although studies with important foodborne metals such as inorganic
[Hg(II)] or organic (CH3 Hg) mercury are lacking. Lactobacilli were evaluated for
their potential to bind these contaminants and the nature of the interaction was
assessed by the use of metal competitors, chemical and enzymatical treatments,
and mutants affected in the cell wall structure. RESULTS: Lactobacillus strains
efficiently bound Hg(II) and CH3 Hg. Mercury binding by Lactobacillus casei BL23
was independent of cell viability. In BL23, both forms of mercury were cell wall
bound. Their interaction was not inhibited by cations and it was resistant to
chelating agents and protein digestion. Lactobacillus casei mutants affected in
genes involved in the modulation of the negative charge of the cell wall anionic
polymer lipoteichoic acid showed increased mercury biosorption. In these mutants,
mercury toxicity was enhanced compared to wild-type bacteria. These data suggest
that lipoteichoic acid itself or the physicochemical characteristics that it
confers to the cell wall play a major role in mercury complexation. CONCLUSION:
This is the first example of the biosorption of Hg(II) and CH3 Hg in lactobacilli
and it represents a first step towards their possible use as agents for
diminishing mercury bioaccessibility from food at the gastrointestinal tract. (c)
2017 Society of Chemical Industry.
PMID- 28423185
TI - Functional identification of activity-regulated, high-affinity glutamine
transport in hippocampal neurons inhibited by riluzole.
AB - Glutamine (Gln) is considered the preferred precursor for the neurotransmitter
pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS.
Here, an activity-regulated, high-affinity Gln transport system is described in
developing and mature neuron-enriched hippocampal cultures that is potently
inhibited by riluzole (IC50 1.3 +/- 0.5 MUM), an anti-glutamatergic drug, and is
blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A
transport inhibitor. K+ -stimulated MeAIB transport displays an affinity (Km )
for MeAIB of 37 +/- 1.2 MUM, saturates at ~ 200 MUM, is dependent on
extracellular Ca2+ , and is blocked by inhibition of voltage-gated Ca2+ channels.
Spontaneous MeAIB transport is also dependent on extracellullar Ca2+ and voltage
gated calcium channels, but is also blocked by the Na+ channel blocker
tetrodotoxin, by Glu receptor antagonists, and by GABA indicating its dependence
on intact neural circuits driven by endogenous glutamatergic activity. The
transport of MeAIB itself does not rely on Ca2+ , but on Na+ ions, and is pH
sensitive. Activity-regulated, riluzole-sensitive spontaneous and K+ -stimulated
transport is minimal at 7-8 days in vitro, coordinately induced during the next 2
weeks and is maximally expressed by days in vitro > 20; the known period for
maturation of the Glu/Gln cycle and regulated pre-synaptic Glu release.
Competition analyses with various amino acids indicate that Gln is the most
likely physiological substrate. Activity-regulated Gln/MeAIB transport is not
observed in astrocytes. The functional identification of activity-regulated, high
affinity, riluzole-sensitive Gln/MeAIB transport in hippocampal neurons may have
important ramifications in the neurobiology of activity-stimulated pre-synaptic
Glu release, the Glu/Gln cycle between astrocytes and neurons, and neuronal Glu
induced excitotoxicity. Cover Image for this issue: doi: 10.1111/jnc.13805.
PMID- 28423188
TI - Intertrial interval duration affects error monitoring.
AB - The purpose of this study was to investigate the effect of varying intertrial
interval (ITI) durations on neural signals of error monitoring, given the
importance of the ITI as a time window for engaging in self-evaluation and
cognitive control. In a between-subjects design, 35 participants were assigned to
one of three ITI durations (short: 768 ms; medium: 1,280 ms; long: 1,792 ms) in a
standard Stroop task while EEG was recorded. Participants in the short-ITI group
demonstrated lower performance accuracy, a reduced error-related negativity (even
when correcting for frequency of errors), lower error-related alpha suppression
during the ITI, and increased post-error slowing. Results indicate that fast
paced trial timing can be disruptive to self-monitoring, perhaps due to capacity
limitations or bottlenecks in processing.
PMID- 28423190
TI - The clinical utility of genome-wide non invasive prenatal screening.
AB - OBJECTIVE: In this study, we expanded conventional cell-free fetal DNA (cfDNA)
based non-invasive prenatal testing (NIPT) to cover the entire genome. We aimed
to compare the performance of the two tests in a large general population of
pregnant women, in order to assess the clinical utility of the genome-wide
screening. METHOD: Genome-wide cfDNA analysis was offered to 12 114 pregnant
women undergoing NIPT for common fetal aneuploidy. Sequencing data were analyzed
using an algorithm optimized to identify aneuploidies and subchromosomal
aberrations. RESULTS: Genome-wide screening allowed detection of 12 (7.4%)
potentially viable clinically relevant chromosomal abnormalities, which would
have remained overlooked if only conventional NIPT had been performed. This
resulted in a statistically significant higher sensitivity (100% vs 92.64%, p <
0.001) than did standard screening. This was achieved without sacrificing the
specificity of the test, which resulted similar to that obtained with standard
cfDNA testing (99.87% vs 99.77%, p = 0.064). CONCLUSION: Genome-wide cfDNA
analysis represents an enhanced screening tool for prenatal detection of
chromosomal abnormalities, allowing identification of clinically relevant
imbalances that are not detectable by conventional cfDNA testing. The results of
this study demonstrate the clinical utility of genome-wide cfDNA analysis. This
level of screening provides a significant higher sensitivity compared to standard
screening while maintaining a high specificity, with the potential to improve
overall pregnancy management. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423189
TI - Computed tomography quantification of tracheal abnormalities in COPD and their
influence on airflow limitation.
AB - PURPOSE: To present a method to automatically quantify tracheal morphology
changes during breathing and investigate its contribution to airflow impairment
when adding CT measures of emphysema, airway wall thickness, air trapping and
ventilation. METHODS: Because tracheal abnormalities often occur localized, a
method is presented that automatically determines the most abnormal trachea
section based on automatically computed sagittal and coronal lengths. In this
most abnormal section, trachea morphology is encoded using four equiangular rays
from the center of the trachea and the normalized lengths of these rays are used
as features in a classification scheme. Consequently, trachea measurements are
used as input for classification into GOLD stages in addition to emphysema, air
trapping and ventilation. A database of 200 subjects distributed across all GOLD
stages is used to evaluate the classification with a k nearest neighbour
algorithm. Performance is assessed in two experimental settings: (a) when only
inspiratory scans are taken; (b) when both inspiratory and expiratory scans are
available. RESULTS: Given only an inspiratory CT scan, measuring tracheal shape
provides complementary information only to emphysema measurements. The best
performing set in the inspiratory setting was a combination of emphysema and
bronchial measurements. The best performing feature set in the inspiratory
expiratory setting includes measurements of emphysema, ventilation, air trapping,
and trachea. Inspiratory and inspiratory-expiratory settings showed similar
performance. CONCLUSIONS: The fully automated system presented in this study
provides information on trachea shape at inspiratory and expiratory CT. Addition
of tracheal morphology features improves the ability of emphysema and air
trapping CT-derived measurements to classify COPD patients into GOLD stages and
may be relevant when investigating different aspects of COPD.
PMID- 28423191
TI - Origins and evolution of innate lymphoid cells: Wardens of barrier immunity.
AB - The identification, in the late 2000s, of innate lymphoid cells (ILCs) as a new
class of non-B, non-T lymphocytes has led to global efforts to understand their
functions, plasticity and evolutionary origins and to define their place within
the leucocyte family. Although this work has uncovered striking similarities in
the developmental cues, lineage-specific transcription factors and functional
capacities of innate and adaptive lymphocytes, it has become clear that ILCs play
a unique and defining role as stewards of barrier defence and that this sets them
apart from their adaptive cousins. This review will explore how the dynamic
environment of barrier surfaces has shaped ILC evolution and functionality. We
highlight the critical importance of the microbiome and the unique role of ILCs
as environmental sensors. We reflect on how these factors may have influenced the
development of ILC2s and barrier immunity in the context of exposure to helminth
parasites that have been driving forces of our evolution throughout human
history. Finally, we argue that the plasticity of ILC function reflects their
role as first responders to environmental change.
PMID- 28423192
TI - Systematic Review of the Safety and Efficacy of Palivizumab among Infants and
Young Children with Cystic Fibrosis.
AB - BACKGROUND: Respiratory syncytial virus (RSV) is a common pathogen in infants
with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection
as the standard of care for infants with CF remains controversial. OBJECTIVE: To
evaluate the efficacy of palivizumab in reducing the incidence of RSV
hospitalization in children with CF who are younger than 2 years. METHODS: Four
electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from
inception until January 31, 2017, for clinical studies investigating the use of
palivizumab in infants with CF aged less than 2 years. The primary outcome was
hospitalization rate due to RSV infection. Secondary outcomes included
hospitalization for respiratory illness, length of hospital stay, safety (adverse
effects), and cost-effectiveness of palivizumab prophylaxis. RESULTS: The review
included a total of 10 studies (six cohort studies, two before-and-after studies,
one cross-sectional study, and one randomized controlled trial) involving 3891
patients with CF. Seven studies reported that palivizumab prophylaxis had a
positive impact on the rate of RSV hospitalization. Five studies (n=3404)
reported that palivizumab prophylaxis significantly reduced the rate of
hospitalization due to RSV infection compared to no prophylaxis. One study (n=5)
demonstrated patients with CF who received palivizumab had no RSV
hospitalization. Another study showed infants with CF receiving palivizumab
(n=117) had a lower risk of hospitalization for RSV infection compared with
premature infants (gestational age < 35 completed weeks) who received palivizumab
(n=4880). CONCLUSIONS: Evidence from the literature suggests that palivizumab may
have a potential role in reducing RSV hospitalization in children aged less than
2 years with CF. Given the lack of overall data, additional research is warranted
to better understand the efficacy and safety of prophylactic palivizumab in
infants with CF.
PMID- 28423193
TI - Is the use of differences in the magnitude of CAL gain appropriate for making
conclusions on the efficacy of non-surgical therapeutic means?
PMID- 28423195
TI - Noninvasive imaging of c(RGD)2 -9R as a potential delivery carrier for
transfection of siRNA in malignant tumors.
AB - The purpose of our study was to develop and evaluate a novel integrin alphav
beta3 -specific delivery carrier for transfection of siRNA in malignant tumors.
We adopted arginine-glycine-aspartate (RGD) motif as a tissue target for specific
recognition of integrin alphanu beta3 . A chimaeric peptide was synthesized by
adding nonamer arginine residues (9-arginine [9R]) at the carboxy terminus of
cyclic-RGD dimer, designated as c(RGD)2 -9R, to enable small interfering RNA
(siRNA) binding. To test the applicability of the delivery carrier in vivo,
c(RGD)2 -9R was labeled with radionuclide of technetium-99m. Biodistribution and
gamma-camera imaging studies were performed in HepG2 xenograft-bearing nude mice.
As results, an optimal 10:1 molar ratio of 99m Tc-c(RGD)2 -9R to siRNA was
indicated by the electrophoresis on agarose gels. 99m Tc-c(RGD)2 -9R/siRNA
remained stable under a set of conditions in vitro. For in vivo study, tumor
radioactivity uptake of 99m Tc-c(RGD)2 -9R/siRNA in nude mice bearing HepG2
xenografts was significantly higher than that of control probe (P < .05). The
xenografts were clearly visualized at 4 hours till 6 hours noninvasively after
intravenous injection of 99m Tc-c(RGD)2 -9R/siRNA, while the xenografts were not
visualized at any time after injection of control probe. It was concluded that
c(RGD)2 -9R could be an effective siRNA delivery carrier. Technetium-99m
radiolabeled-delivery carrier represents a potential imaging strategy for RNAi
based therapy.
PMID- 28423196
TI - Melatonin enhances neural stem cell differentiation and engraftment by increasing
mitochondrial function.
AB - Neural stem cells (NSCs) are regarded as a promising therapeutic approach to
protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such
as Parkinson's disease and Alzheimer's disease (PD and AD, respectively).
However, new research suggests that NSC differentiation is required to make this
strategy effective. Several studies have demonstrated that melatonin increases
mature neuronal markers, which reflects NSC differentiation into neurons.
Nevertheless, the possible involvement of mitochondria in the effects of
melatonin during NSC differentiation has not yet been fully established. We
therefore tested the impact of melatonin on NSC proliferation and differentiation
in an attempt to determine whether these actions depend on modulating
mitochondrial activity. We measured proliferation and differentiation markers,
mitochondrial structural and functional parameters as well as oxidative stress
indicators and also evaluated cell transplant engraftment. This enabled us to
show that melatonin (25 MUM) induces NSC differentiation into oligodendrocytes
and neurons. These effects depend on increased mitochondrial mass/DNA/complexes,
mitochondrial respiration, and membrane potential as well as ATP synthesis in
NSCs. It is also interesting to note that melatonin prevented oxidative stress
caused by high levels of mitochondrial activity. Finally, we found that melatonin
enriches NSC engraftment in the ND mouse model following transplantation. We
concluded that a combined therapy involving transplantation of NSCs pretreated
with pharmacological doses of melatonin could efficiently restore neuronal cell
populations in PD and AD mouse models depending on mitochondrial activity
promotion.
PMID- 28423197
TI - Diabetic kidney transplant recipients: Impaired infection control and increased
alloreactivity.
AB - BACKGROUND: Post-transplantation diabetes mellitus (PTDM) has been associated
with inferior patient and allograft outcomes. However, previous studies did not
identify differences in infection control and alloreactivity. METHODS: We studied
449 kidney transplant recipients (KTRs) between 2005 and 2013. Fifty (11.1%) KTRs
were diagnosed with PTDM and 60 (13.4%) KTRs with pre-existing diabetes. Samples
were collected pretransplantation, at +1, +2, +3 months post-transplantation. CMV
specific and alloreactive T cells were quantified by interferon-gamma Elispot
assay. Lymphocyte subpopulations were quantified by flow cytometry. RESULTS: Upon
multivariate analysis, age, obesity, and the use of tacrolimus increased the risk
of PTDM (P<.05). KTRs with pre-existing diabetes/PTDM showed higher rates of
sepsis (P<.01). Total CD3+ and CD4+ T cell counts were significantly lower in
KTRs with PTDM/pre-existing diabetes post-transplantation (P<.05). No differences
were observed for CMV-specific T cells between any group (P>.05). KTRs developing
PTDM showed increased frequencies of alloreactive T-cells post-transplantation
(P<.05). CONCLUSIONS: Our results suggest higher rates of infection in KTRs with
pre-existing diabetes/PTDM that may be attributed to impaired overall immunity.
Higher frequencies of alloreactive T cells contribute to inferior long-term
outcomes. As acute rejection, but not pre-existing diabetes/PTDM, was associated
with inferior allograft survival and function, maintaining adequate
immunosuppression to prevent rejection seems important.
PMID- 28423199
TI - Chemical Synthesis of Modified Hyaluronic Acid Disaccharides.
AB - Herein we report a chemical synthesis towards new modified hyaluronic acid
oligomers by using only commercially available d-glucose and d-glucosamine
hydrochloride. The various protected hyaluronic acid disaccharides were
synthesized bearing new functional groups at C-6 of the beta-d-glucuronic acid
moiety with a view to structure-related biological activity tests. The orthogonal
protecting group pattern allows ready access to the corresponding higher
oligomers. Also, 1 H NMR studies of the new derivatives demonstrated the effect
of the various functional groups on the intramolecular electronic environment.
PMID- 28423198
TI - An estradiol-inducible promoter enables fast, graduated control of gene
expression in fission yeast.
AB - The fission yeast Schizosaccharomyces pombe lacks a diverse toolkit of inducible
promoters for experimental manipulation. Available inducible promoters suffer
from slow induction kinetics, limited control of expression levels and/or a
requirement for defined growth medium. In particular, no S. pombe inducible
promoter systems exhibit a linear dose-response, which would allow expression to
be tuned to specific levels. We have adapted a fast, orthogonal promoter system
with a large dynamic range and a linear dose response, based on beta-estradiol
regulated function of the human oestrogen receptor, for use in S. pombe. We show
that this promoter system, termed Z3 EV, turns on quickly, can reach a maximal
induction of 20-fold, and exhibits a linear dose response over its entire
induction range, with few off-target effects. We demonstrate the utility of this
system by regulating the mitotic inhibitor Wee1 to create a strain in which cell
size is regulated by beta-estradiol concentration. This promoter system will be
of great utility for experimentally regulating gene expression in fission yeast.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423200
TI - CD80CD86 deficiency disrupts regulatory CD4+FoxP3+T cell homoeostasis and induces
autoimmune-like alopecia.
AB - Alopecia areata (AA) is an autoimmune disease that results in spot baldness in
humans. Adequate animal models for AA are currently lacking. The objective of
this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in
C57BL/6.CD80CD86-deficient (B6.CD80CD86-/- ) mice. Incidence and severity of
alopecia were analysed in 58 B6.CD80CD86-/- mice using histological examination,
flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR
and CD25 inhibition test. Both male and female B6.CD80CD86-/- mice showed almost
100% incidence of hair loss at 40 weeks of age. Moreover, CD4+FoxP3+Treg (Treg)
cell population in B6.CD80CD86-/- mice was significantly lower than in B6 mice,
which presumably underlined autoimmune reaction. Histologically, B6.CD80CD86-/-
mice showed CD4+ and CD8+ T-cell infiltration around terminal follicle region and
exhibited hair follicle destruction in the anagen or catagen stage. Negative
correlation between the number of CD4+FoxP3+ Tregs and ALA was confirmed by the
CD25 depletion test in B6 mice, as follicle destruction was similar to that
observed in B6.CD80CD86-/- animals. CD80CD86 deficiency disrupted CD4+FoxP3+ Treg
homoeostasis and prompted the development of ALA. We demonstrated that
B6.CD80CD86-/- mice might have several advantages as an ALA model, because they
exhibited high incidence of disease phenotype and epipathogenesis similar to that
observed in human AA.
PMID- 28423201
TI - Highly Enantioselective Allylation of Ketones: An Efficient Approach to All
Stereoisomers of Tertiary Homoallylic Alcohols.
AB - An optimized protecting group for allylboronates allowed the use of ketones in
order to synthesize all isomers of quaternary homoallylic alcohols with high
enantioselectivities. All symmetric isomers of the allylboronate were prepared in
high yields and diastereoselectivities using Sn 2' reactions. The improved
reactivity of the novel protecting group was verified by following the reaction
kinetics with 1 H NMR spectroscopy. Mechanistic studies using DFT calculations
were conducted to investigate the new findings. Thus, the stereochemical outcome
and enhanced reactivity can be rationalized.
PMID- 28423202
TI - In some places, in some cases, and at some times, harmful algal blooms are the
greatest threat to inland water quality.
PMID- 28423203
TI - Corrigendum.
PMID- 28423204
TI - New Motifs in Deoxydehydration: Beyond the Realms of Rhenium.
AB - The deoxydehydration (DODH) reaction remains one of the most efficient methods of
reducing the oxygen content of biomass while keeping important functionality in
place. This reaction is traditionally catalysed by high-valent oxo-rhenium
species. Recent research into heterogeneous rhenium-based catalysts for DODH
demonstrates their ability to rival and in some cases surpass their homogeneous
counterparts. Furthermore, catalysts based on the metals molybdenum and vanadium
show great potential as inexpensive alternatives to rhenium catalysts. In this
Minireview, we detail the recent developments within the field of DODH with
particular emphasis on discoveries outside the realms of rhenium.
PMID- 28423206
TI - Folic acid - Who does what with methotrexate?
PMID- 28423205
TI - The impact of biogas and fuelwood use on institutional kitchen air quality in
Kampala, Uganda.
AB - Experts have suggested that microscale biogas systems offer a source of renewable
energy that improves indoor air quality, but such impacts have not been directly
measured. This study documented cooking behaviors and measured 2.5-MUm
particulate matter (PM2.5 ), carbon monoxide (CO), and sulfur dioxide (SO2 )
concentrations within 14 institutional kitchens in Kampala, Uganda, that prepare
meals using biogas (n=5), a mixture of biogas and fuelwood (n=3), and fuelwood
(n=6). Small institutions (10-30 people) with biogas kitchens had 99% lower
concentrations of PM2.5 (21 MUg/m3 ) than fuelwood kitchens (3100 MUg/m3 ).
Larger institutions (>100 people) had biogas systems that produced insufficient
gas and relied on fuelwood to meet over 90% of their energy needs. PM2.5
concentrations in these biogas-firewood kitchens were equivalent to
concentrations in fuelwood kitchens. Although concentrations of hydrogen sulfide
(H2 S) in biogas were as high as 2000 ppm, 75% of systems had undetectable H2 S
levels (<100 ppm) in the biogas. Kitchens using biogas with high H2 S had
correspondingly higher SO2 concentrations in the kitchen air. However, even the
highest SO2 concentration in biogas kitchens (150 MUg/m3 ) was lower than SO2
concentration in fuelwood kitchens (390 MUg/m3 ). The results suggest that biogas
systems can offer air quality improvements if sized properly for energy demands.
PMID- 28423207
TI - Nanospray liquid chromatography/tandem mass spectrometry analysis of steroids
from gray whale blubber.
AB - RATIONALE: Analysis of steroids from precious blubber biopsies obtained from
marine mammals, especially endangered species, can provide valuable information
on their endocrine status. Challenges with currently used ELISA methodology
include lack of absolute quantitation and incompatibility with multiple steroids
analysis due to limited biopsy mass. Development of a sensitive, accurate
analytical method for this purpose is critical. METHODS: A nanospray liquid
chromatography/tandem mass spectrometry (nanoLC/MS/MS) method was validated for
sensitive, specific and quantitative analysis of three steroid hormones, without
derivatization, extracted from 50 mg blubber samples. Data was acquired with an
LTQ XL ion trap mass spectrometer in positive ion mode, using single reaction
monitoring. All three steroids were analyzed in a single run. Cholic acid was
used as a surrogate internal standard for quantitation due to its steroidal
structure and lack of measurable endogenous levels in blubber. RESULTS: The
lowest limits of quantitation for progesterone, testosterone, and hydrocortisone
were significantly improved compared to previous studies using conventional
LC/MS/MS. The lowest limit of detection was 7 fg/MUL using a 1 MUL injection
volume. Calibration curves for steroid quantification showed good linearity (r2
>0.99) between 14 and 3620 fg/MUL, and accuracy was <20% for interday and <10%
for intraday. After validation, the method was successfully applied to
quantification of steroids in gray whale blubber samples. CONCLUSIONS: The
nanoLC/MS/MS method is more sensitive than traditional LC/MS/MS for steroid
analysis. It is also compatible with other important biopsy analyses due to its
small blubber mass requirement. This will benefit the reproductive and stress
assessments for all marine mammals, particularly endangered populations.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423208
TI - Combined activity of temozolomide and the mTOR inhibitor temsirolimus in
metastatic melanoma involves DKK1.
AB - The BRAFV600E inhibitor vemurafenib achieves remarkable clinical responses in
patients with BRAF-mutant melanoma, but its effects are limited by the onset of
drug resistance. In the case of resistance, chemotherapy can still be applied as
second line therapy. However, it yields low response rates and strategies are
urgently needed to potentiate its effects. In a previous study, we showed that
the inhibition of the PI3K-AKT-mTOR pathway significantly increases sensitivity
of melanoma cells to chemotherapeutic drugs (J. Invest. Dermatol. 2009, 129,
1500). In this study, the combination of the mTOR inhibitor temsirolimus with the
chemotherapeutic agent temozolomide significantly increases growth inhibition and
apoptosis in melanoma cells compared to temsirolimus or temozolomide alone. The
combination of temozolomide with temsirolimus is not only effective in
established but also in newly isolated and vemurafenib-resistant metastatic
melanoma cell lines. These effects are associated with the downregulation of the
anti-apoptotic protein Mcl-1 and the upregulation of the Wnt antagonist Dickkopf
homologue 1 (DKK1). Knock-down of DKK1 suppresses apoptosis induction by the
combination of temsirolimus and temozolomide. These data suggest that the
inhibition of the mTOR pathway increases sensitivity of melanoma cells towards
temozolomide. Chemosensitisation is associated with enhanced expression of the
Wnt antagonist DKK1.
PMID- 28423209
TI - The R2R3-MYB transcription factor MdMYB73 is involved in malate accumulation and
vacuolar acidification in apple.
AB - Malate, the predominant organic acid in many fruits, is a crucial component of
the organoleptic quality of fruit, including taste and flavor. The genetic and
environmental mechanisms affecting malate metabolism in fruit cells have been
studied extensively. However, the transcriptional regulation of malate
metabolizing enzymes and vacuolar transporters remains poorly understood. Our
previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and
vacuolar acidification by directly activating vacuolar transporters, including
MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a
MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It
was subsequently found that MdMYB73 protein bound directly to the promoters of
MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase
subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating
their expression and thereby enhancing their activities. Analyses of transgenic
apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar
pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon
downstream target genes. These findings help to elucidate how MdMYB73 directly
modulates the vacuolar transport system to affect malate accumulation and
vacuolar pH in apple.
PMID- 28423210
TI - Intrinsic incompatibilities evolving as a by-product of divergent ecological
selection: Considering them in empirical studies on divergence with gene flow.
AB - The possibility of intrinsic barriers to gene flow is often neglected in
empirical research on local adaptation and speciation with gene flow, for example
when interpreting patterns observed in genome scans. However, we draw attention
to the fact that, even with gene flow, divergent ecological selection may
generate intrinsic barriers involving both ecologically selected and other
interacting loci. Mechanistically, the link between the two types of barriers may
be generated by genes that have multiple functions (i.e., pleiotropy), and/or by
gene interaction networks. Because most genes function in complex networks, and
their evolution is not independent of other genes, changes evolving in response
to ecological selection can generate intrinsic barriers as a by-product. A
crucial question is to what extent such by-product barriers contribute to
divergence and speciation-that is whether they stably reduce gene flow. We
discuss under which conditions by-product barriers may increase isolation.
However, we also highlight that, depending on the conditions (e.g., the amount of
gene flow and the strength of selection acting on the intrinsic vs. the
ecological barrier component), the intrinsic incompatibility may actually
destabilize barriers to gene flow. In practice, intrinsic barriers generated as a
by-product of divergent ecological selection may generate peaks in genome scans
that cannot easily be interpreted. We argue that empirical studies on divergence
with gene flow should consider the possibility of both ecological and intrinsic
barriers. Future progress will likely come from work combining population genomic
studies, experiments quantifying fitness and molecular studies on protein
function and interactions.
PMID- 28423211
TI - "Driving to the edge of the cliff": Transgender mental health.
PMID- 28423212
TI - Persistent Radicals of Self-assembled Benzophenone bis-Urea Macrocycles:
Characterization and Application as a Polarizing Agent for Solid-state DNP MAS
Spectroscopy.
AB - UV-irradiation of a self-assembled benzophenone bis-urea macrocycle generates MUm
amounts of radicals that persist for weeks under ambient conditions. High-field
EPR and variable-temperature X-band EPR studies suggest a resonance stabilized
radical pair through H-abstraction. These endogenous radicals were applied as a
polarizing agent for magic angle spinning (MAS) dynamic nuclear polarization
(DNP) NMR enhancement. The field-stepped DNP enhancement profile exhibits a sharp
peak with a maximum enhancement of epsilonon/off =4 superimposed on a nearly
constant DNP enhancement of epsilonon/off =2 over a broad field range. This
maximum coincides with the high field EPR absorption spectrum, consistent with an
Overhauser effect mechanism. DNP enhancement was observed for both the host and
guests, suggesting that even low levels of endogenous radicals can facilitate the
study of host-guest relationships in the solid-state.
PMID- 28423213
TI - Systemic tumor-targeted sodium iodide symporter (NIS) gene therapy of
hepatocellular carcinoma mediated by B6 peptide polyplexes.
AB - BACKGROUND: Nonviral polymer-based gene transfer represents an adaptable system
for tumor-targeted gene therapy because various design strategies of shuttle
systems, together with the mechanistic concept of active tumor targeting, lead to
improved gene delivery vectors resulting in higher tumor specificity, efficacy
and safety. METHODS: Using the sodium iodide symporter (NIS) as a theranostic
gene, nonviral gene delivery vehicles based on linear polyethylenimine (LPEI),
polyethylene glycol (PEG) and coupled to the synthetic peptide B6 (LPEI-PEG-B6),
which specifically binds to tumor cells, were investigated in a hepatocellular
carcinoma xenograft model for tumor selectivity and transduction efficiency.
RESULTS: In vitro incubation of three different tumor cell lines with LPEI-PEG
B6/NIS resulted in significant increase in iodide uptake activity compared to
untargeted and empty vectors. After establishment of subcutaneous HuH7 tumors,
NIS-conjugated nanoparticles were injected intravenously followed by analysis of
radioiodide biodistribution using 123 I-scintigraphy showing significant
perchlorate-sensitive iodide accumulation in tumors of LPEI-PEG-B6/NIS-treated
mice (8.0 +/- 1.5% ID/g 123 I; biological half-life of 4 h). After four cycles of
repetitive polyplex/131 I applications, a significant delay of tumor growth was
observed, which was associated with markedly improved survival in the therapy
group. CONCLUSIONS: These results clearly demonstrate that systemic in vivo NIS
gene transfer using nanoparticle vectors coupled to B6 tumor targeting ligand is
capable of inducing tumor-specific radioiodide uptake. This promising gene
therapy approach opens the exciting prospect of NIS-mediated radionuclide therapy
in metastatic cancer, together with the possibility of combining several
targeting ligands to enhance selective therapeutic efficacy in a broad field of
cancer types with various receptor expression profiles.
PMID- 28423214
TI - Plasmodium falciparum OTU-like cysteine protease (PfOTU) is essential for
apicoplast homeostasis and associates with noncanonical role of Atg8.
AB - The metabolic pathways associated with the mitochondrion and the apicoplast in
Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as
suitable drug targets. In the present study, we have identified functional role
of a novel ovarian tumour unit (OTU) domain-containing cysteine protease of
Plasmodium falciparum (PfOTU). A C-terminal regulatable fluorescent affinity tag
on native protein was utilised for its localization and functional
characterization. Detailed studies showed vesicular localization of PfOTU and its
association with the apicoplast. Degradation-tag mediated knockdown of PfOTU
resulted in abnormal apicoplast development and blocked development of parasites
beyond early-schizont stages in subsequent cell cycle; downregulation of PfOTU
hindered apicoplast protein import. Further, the isoprenoid precursor-mediated
parasite growth-rescue experiments confirmed that PfOTU knockdown specifically
effect development of functional apicoplast. We also provide evidence for a
possible biological function of PfOTU in membrane deconjugation of Atg8, which
may be linked with the apicoplast protein import. Overall, our results show that
the PfOTU is involved in apicoplast homeostasis and associates with the
noncanonical function of Atg8 in maintenance of parasite apicoplast.
PMID- 28423215
TI - Breaking down the stigma of mental health nursing: A qualitative study reflecting
opinions from western australian nurses.
AB - WHAT IS KNOWN ON THE SUBJECT?: The rate of mental illness in the general
population is ever increasing Mental health nurses are ageing, and this is not a
preferred career for new graduates; thus, recruitment and retention of mental
health nurses is declining Stigma is attached to the view of mental illness and
the role of a mental health nurse. If this stigma can be reduced, it may provide
an opportunity for the profession to become more popular and assist recruitment
in this area WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Previous research has
focused on why mental health nurses leave the profession which has not provided
successful results This study adopts a new way of working whereby we gathered
opinions from current mental health nurses focusing on why they originally wanted
to work in mental health WHAT ARE THE IMPLICATIONS FOR PRACTICE?: New findings
presented in this paper will guide improvements in nurse training, policy
development for mental health services and improve recruitment of the next
generation of mental health nurses The findings provide a strong message that in
order to entice others to work in mental health, we need to first address
breaking down the stigma related to mental health nursing ABSTRACT: Introduction
A lack of understanding surrounding the role of mental health nursing is
associated with recruitment and retention challenges. Additional complexities
include stigma related to the role, an ageing workforce and dearth of graduates
keen to pursue this career. Scientific Rational Previous research has focused on
why nurses leave the profession which has not provided necessary solutions. There
is a need to instead explore why nurses originally chose a career in mental
health. Aim of study This qualitative study focused on opinions and experiences
of existing mental health nurses to determine what could be performed to entice
nurses to choose mental health. Methods A cross-sectional design involving a
brief interview was conducted with 192 Western Australian nurses from one public
mental health service. Results Thematic analysis revealed an overarching theme
"breaking down stigma" and additional themes of: "visibility of mental health
nursing" and "growing mental health nursing." Subthemes under "visibility"
included "self-promotion" plus "industry and university promotion," whereas
subthemes related to "growing" focused upon "improving the student experience."
Finally, "recognizing the mental health specialty" was identified for an
attractive career pathway. Discussion This study adds to international evidence
and showcases unique insights from mental health nurses into why they chose a
career in mental health whilst previously replicated research focused on why
nurses chose to leave. Implications for practice Findings suggest that before we
can entice nurses to choose mental health, there is urgency to reduce stigma
related to the role. "Breaking down stigma" will allow the role to become more
visible and be represented in a more positive authentic manner. New findings in
this paper will drive improvements of future nurse education, policy planning and
recruitment design for the next generation of mental health nurses.
PMID- 28423216
TI - Tokenistic or genuinely effective? Exploring the views of voluntary sector staff
regarding the emerging peer support worker role in mental health.
AB - WHAT IS KNOWN ON THE SUBJECT: The introduction of PSWs within mental health
services has grown substantially both internationally and locally; however, no
recognized studies have focused on the evolvement of this role within a Northern
Ireland (NI) context. Research is increasingly focusing on service users' and
PSWs perspectives on mental health service provision. Despite this, few studies
exist which exclusively report staff views in relation to the PSW role. WHAT THE
PAPER ADDS TO EXISTING KNOWLEDGE: Results of the current study identified varying
perspectives on the peer role. Some participants believed that the PSW role was
tokenistic; others opposed these views, highlighting the value of this role.
Clearly defined job descriptions and the importance of ensuring the PSW is a
cohesive part of the team and not an "add on," was identified as imperative to
avoid tokenistic practice. Provision of a flexible working environment, both
sensitive and responsive to the peers' own mental health needs, was identified as
significant in order for the peer to fulfil their role successfully. IMPLICATIONS
FOR PRACTICE: Services introducing PSWs within teams should engage with nursing
staff at all organizational levels in the role development process to minimize
the risk of tokenism, for example, the PSW role not integrated or valued within
teams. Clearly defined job/role specifications for PSWs should be devised to
ensure that both the PSW and the mental health nursing team have a shared
understanding regarding this role. ABSTRACT: Aim Peer support worker (PSW) roles
are gaining recognition internationally as a valuable component in mental health
service delivery. The aim of this study was to explore the views of mental health
voluntary sector staff regarding the emergence of this role. Method A qualitative
research design was used. A purposive sample was employed. Semi-structured
interviews were undertaken with 10 staff members in various positions in two
voluntary mental health organizations. Interview transcripts were analysed
thematically. Results Views varied on the PSW role with some participants stating
that it was tokenistic, whereas others highlighted the value of its contribution.
Participants' expressed concerns regarding professional boundaries and
organizational cultural challenges that PSWs may encounter in their role. The
provision of reasonable adjustments was recommended as an integral support
mechanism. Conclusion Successful integration of the PSW requires careful
consideration of the role, the workplace environment and the unique needs of the
peer, to prevent the role becoming constrained and diluted. Implications for
practice The PSW role may impact the traditional delivery of mental health
nursing services. It is therefore essential that nurses are cognizant of these
potential challenges to successfully facilitate the integration of PSWs in
practice.
PMID- 28423217
TI - In-vitro discrimination of wound associated bacteria by volatile compound
profiling using Selected Ion Flow Tube - Mass Spectrometry.
AB - AIMS: To determine if bacterial species responsible for clinically relevant wound
infection produce specific volatile profiles that would allow their speciation.
METHODS AND RESULTS: Selected-Ion Flow Tube-Mass Spectrometry in full mass scan
mode was used to analyse headspace gases produced by wound-associated bacteria
grown in vitro, so as to enable identification of bacterial volatile product ion
profiles in the resulting mass spectra. Applying multivariate statistical
analysis (hierarchical clustering and principal component analysis) to the
resultant mass spectra enabled clear speciation. Moreover, bacterial volatile
product ions could be detected from artificially contaminated wound dressing
material, although the pattern of product ions detected was influenced by culture
conditions. CONCLUSIONS: Using selected product ions from the SIFT-MS mass
spectra it is possible to discriminate wound-associated bacterial species grown
under specific in vitro culture conditions. This article is protected by
copyright. All rights reserved.
PMID- 28423218
TI - Strain specific variation in plant growth promoting volatile organic compound
production by five different Pseudomonas spp. as confirmed by response of Vigna
radiata seedlings.
AB - AIM: Analysis of blend of volatile organic compounds (VOCs) released by
Pseudomonas spp. with growth promoting effect in Vigna radiata seedlings. METHODS
AND RESULTS: Plant growth promoting activity of VOCs produced by five different
Pseudomonas spp. was investigated by I-plate technique. VOCs produced by
different organisms were extracted by various solvents (methanol, ethyl acetate,
hexane and butanol) were identified by gas chromatography-mass spectrometric (GC
MS) analysis. The major VOCs identified were undecane, nonadecane, hexacosane,
tetradecane, heptacosane, pentadecane, dodecane and tetratetracontane. The
cultural conditions for the production of VOCs with plant growth enhancement
effect were optimized and further confirmed using pure pentadecane as a candidate
VOC. CONCLUSIONS: The study provides insight into plant beneficial effect of VOCs
produced by Pseudomonas spp. Remarkable modulation in production of VOCs with
plant growth promoting effect by rhizobacteria was found to be depend on
bacterial strain and its concentration. This article is protected by copyright.
All rights reserved.
PMID- 28423219
TI - 2017 American Transplant Congress Abstracts.
PMID- 28423220
TI - Gas-phase fragmentations of N-methylimidazolidin-4-one organocatalysts.
AB - N-methylimidazolidin-4-one organocatalysts were studied in the gas phase.
Protonated and sodium-cationized (sodiated) molecules are conveniently accessible
by electrospray mass spectrometry. Protonation enables three different closed
shell paths of ring cleavage leading to iminium ions. The fragmentation pattern
is largely unaffected by exocyclic substituents and thus is valuable to
characterize the substance type as N-methylimidazolidin-4-ones. Sodiated species
show a distinctly different fragmentation that is less useful for
characterization purposes: apart from signal loss due to dissociation of Na+ ,
the observation of benzyl radical loss is by far predominant. Only in absence of
a benzyl substituent, an analogue of the third ring cleavage (loss of [C2 H5 NO])
is observed. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423221
TI - Facial asymmetry in head and neck rhabdomyosarcoma survivors.
AB - INTRODUCTION: Radiotherapy is essential for achieving and maintaining local
control in head and neck rhabdomyosarcoma (HNRMS) patients. However, radiotherapy
may cause outgrowth disturbances of facial bone and soft tissue, resulting in
facial asymmetry. The aim of this study was to develop a method to visualize and
measure facial asymmetry in HNRMS survivors using three-dimensional (3D) imaging
techniques. METHODS: Facial deformity was evaluated in a multidisciplinary
clinical assessment of 75 HNRMS survivors, treated with external beam
radiotherapy (EBRT, n = 26) or Ablative surgery, MOulage brachytherapy, and
REconstruction (AMORE, n = 49). Individual facial asymmetry was measured using 3D
photogrammetry and expressed in a raw asymmetry index and a normalized sex-age
ethnicity-matched asymmetry signature weight. Facial asymmetry was also compared
between British and Dutch controls and between survivors and their matched
controls. RESULTS: Facial asymmetry was more pronounced with increasing age (P <
0.01) in British controls compared with Dutch controls (P = 0.04). Survivors
developed more facial asymmetry than matched controls (P < 0.001). The clinical
assessment of facial deformity correlated with the raw asymmetry index (r = 0.60,
P < 0.001). DISCUSSION: 3D imaging can be used for objective measurement of
facial asymmetry in HNRMS survivors. The raw asymmetry index correlated with a
clinical assessment of facial deformity. Comparisons between treatment groups
seemed inappropriate given the differences in facial asymmetry between British
and Dutch controls. In future studies, pretreatment images could act as matched
controls for posttreatment evaluation.
PMID- 28423222
TI - Persistent and Developing Sleep Problems: A Prospective Cohort Study on the
Relationship to Poor Outcome in Patients Attending a Pain Clinic with Chronic Low
Back Pain.
AB - Sleep problems are common in people with low back pain (LBP); however, the
mechanisms of how sleep influences pain are complex. To date there is a lack of
prospective research on the timing and development of sleep problems in those who
have LBP; such information would be useful to identify individuals at risk for
poor outcomes. Our aims are to investigate the predictive role of sleep problems
on self-report recovery and pain intensity using logistic regression reporting
odds ratios (ORs). An observational cohort of 761 chronic LBP patients recruited
from a pain management clinic participated, and they completed data at baseline
and at 6-month follow-up (n = 682). Results show increased odds for reported
nonrecovery (OR 1.52) and pain intensity (OR 2.69) among those who reported sleep
problems at baseline. Further analysis on the experience of sleep problems
through time showed that those with developing sleep problems (ie, no sleep
problems at baseline but reported sleep problems at follow-up) were at increased
odds for reporting nonrecovery (OR 2.17) and pain intensity (OR 2.95), as were
those who reported sleep problems at both baseline and follow-up, for recovery
(OR 2.88) and pain intensity (OR 3.45). Those with resolving sleep problems (ie,
sleep problems present at baseline but not at follow-up) were at decreased odds
for nonrecovery (OR 0.50) and pain intensity (0.49). Presenting, persistent, and
developing sleep problems have a significant impact on recovery for those with
LBP. Clinicians may wish to consider treatment options that can address sleep
problems.
PMID- 28423223
TI - Implementation and preliminary effectiveness of a real-time pain management
smartphone app for adolescents with cancer: A multicenter pilot clinical study.
AB - BACKGROUND: Pain in adolescents with cancer (12-18 years) is common and
negatively impacts health-related quality of life (HRQL). The Pain Squad+
smartphone app, which provides adolescents with real-time pain self-management
support, was developed to address this issue. This study evaluated the
implementation of the app to inform a future randomized controlled trial (RCT)
and obtain treatment effect estimates for pain intensity, pain interference,
HRQL, and self-efficacy. PROCEDURE: A one-group baseline/poststudy design with 40
adolescents recruited from two pediatric tertiary care centers was used. Baseline
questionnaires were completed and adolescents used the app at least twice daily
for 28 days, receiving algorithm-informed self-management advice depending on
their reported pain. A nurse received alerts in response to sustained pain and
contacted adolescents to assist in pain care. Poststudy questionnaires were
completed. Descriptive analyses, with exploratory inferential testing conducted
on health outcome data, were used to address study aims. RESULTS: Most (40/52;
77%) eligible adolescents participated. Two participants withdrew participation.
Intervention fidelity was impacted by technical difficulties (occurring for 15%
of participants) and a prolonged time for nurse contact in the event of sustained
pain. Adherence to pain reporting was 68.8 +/- 38.1%. Outcome measure completion
rates were high and the intervention was acceptable to participants. Trends in
improvements in pain intensity, pain interference, and HRQL were significant,
with effect sizes of 0.23-0.67. CONCLUSIONS: Implementation of Pain Squad+ is
feasible and the app appears to improve pain-related outcomes for adolescents
with cancer. A multicenter RCT will be undertaken to examine app effectiveness.
PMID- 28423224
TI - Facial and extrafacial involvement of lupus miliaris disseminatus faciei with
Kaposi's sarcoma-like lesions.
PMID- 28423225
TI - Exercise interventions for patients with pediatric cancer during inpatient acute
care: A systematic review of literature.
AB - Physical inactivity has been shown to exacerbate negative side effects
experienced by pediatric patients undergoing cancer therapy. Exercise
interventions are being created in response. This review summarizes current
exercise intervention data in the inpatient pediatric oncology setting. Two
independent reviewers collected literature from three databases, and analyzed
data following the PRISMA statement for systematic reviews and meta-analyses. Ten
studies were included, representing 204 patients. Good adherence, positive trends
in health status, and no adverse events were noted. Common strategies included
individual, supervised, combination training with adaptability to meet
fluctuating patient abilities. We recommend that general physical activity
programming be offered to pediatric oncology inpatients.
PMID- 28423226
TI - RVX 208: A novel BET protein inhibitor, role as an inducer of apo A-I/HDL and
beyond.
AB - Low-density cholesterol (LDL) has been the prime target of currently available
lipid-lowering therapies although current research is expanding the focus beyond
LDL lowering and has included high-density cholesterol (HDL) also as the target.
Bromo and extra-terminal (BET) proteins are implicated in the regulation of
transcription of several regulatory genes and regulation of proinflammatory
pathways. As atherosclerosis is an inflammatory pathway and studies showed that
BET inhibition has a role in inhibiting inflammation, the concept of BET
inhibition came in the field of atherosclerosis. RVX 208 is a novel, orally
active, BET protein inhibitor and the only BET inhibitor currently available in
the field of atherosclerosis. RVX 208 acts primarily by increasing apo A-I
(apolipoprotein A-I) and HDL levels. RVX 208 has a novel action of increasing
larger, more cardio-protective HDL particles. Post hoc analysis of Phase II
trials also showed that RVX 208 reduced major adverse cardiovascular events
(MACE) in treated patients, over and above that of apo A-I/HDL increasing action.
This MACE reducing actions of RVX 208 were largely due to its novel anti
inflammatory actions. Currently, a phase III trial, BETonMACE, is recruiting
patients to look for the effects of RVX 208 in patients with increased risk of
atherosclerotic cardiovascular disease. So BET inhibitors act in multiple ways to
inhibit and modulate atherosclerosis and would be an emerging and potential
option in the management of multifactorial disease like coronary artery disease
by inhibiting a single substrate. But we need long-term phase III trial data's to
look for effects on real-world patients.
PMID- 28423227
TI - A national survey of screening and management of hypogammaglobulinemia in
Canadian transplantation centers.
AB - BACKGROUND: Infection remains one of the most common transplant-related causes of
death in patients undergoing transplantation. Secondary hypogammaglobulinemia
(HGG) as a component of immune suppression and deficiency is associated with both
solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT).
Available data and clinical experience for the supplementation of immunoglobulin
(Ig) in these patients is conflicting, and differing clinical opinion accounts
for non-uniform practice in the use of Ig treatment. We aimed to survey lead
transplant practitioners for current practice around polyvalent Ig use in post
transplant recipients across Canada. METHODS: We performed a survey study using
short questionnaires to estimate rate of screening of HGG, use of polyvalent Ig,
and physician's opinion on Ig treatment and infection prevention. Directors of 24
SOT and 23 HCT centers across Canada were invited to participate in the survey
via an electronic mail. RESULTS: Overall response rate was 63.8%. Twenty percent
of SOT programs routinely measured Ig levels pre-transplant compared to 33% of
allogeneic (allo-) and 21% of autologous (auto-) HCT programs. Post-transplant Ig
levels were measured in 13%, 75%, and 29% in SOT, allo-HCT, and auto-HCT,
respectively. The SOT and auto-HCT groups indicated that they do not prescribe Ig
therapy (100% and 86%), contrary to the allo-HCT group (42%). Of the respondents
in the SOT, allo-HCT, and auto-HCT groups, 60%, 67%, and 36%, respectively,
thought infections could be prevented with intravenous immunoglobulins (IVIg). A
majority of respondents indicated they would be interested in participating in a
randomized controlled trial evaluating the use of IVIg in the SOT and in both HCT
groups (100%, 83%, and 57%, respectively). CONCLUSIONS: Our study shows
significant variation in practice between SOT and HCT centers with respect to
screening and management of HGG. There is willingness to participate in a
randomized controlled trial to address whether Ig treatment reduces infection in
post-transplant recipients.
PMID- 28423228
TI - Targeting DNA-Dependent Protein Kinase for Cancer Therapy.
AB - The catalytic activity of DNA-dependent protein kinase (DNA-PK) is critical to
its ability to repair lethal DNA double-strand breaks (DSBs). This includes
repair of DSB lesions resulting from oxidative stress, oncogene-induced
transcription, or following therapeutic treatment of cancer cells. Armed with
this knowledge, many attempts have been made to identify small-molecule
inhibitors of DNA-PK activity as an approach to induce tumour chemo- and
radiosensitisation. This review examines the structures of known reversible and
irreversible inhibitors, including those based on chromen-4-one, arylmorpholine,
and benzaldehyde scaffolds. DNA-PK catalytic inhibitors, such as VX-984 (8-[(1S)
2-[[6-(4,6-dideuterio-2-methylpyrimidin-5-yl)pyrimidin-4-yl]amino]-1
methylethyl]quinoline-4-carboxamide) and M3814 ((S)-[2-chloro-4-fluoro-5-(7
morpholinoquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol), have now
progressed into clinical development which should help to further advance our
understanding of whether this approach is a promising therapeutic strategy for
the treatment of cancer.
PMID- 28423229
TI - Profile and outcome of first 109 cases of paediatric acute liver failure at a
specialized paediatric liver unit in India: Methodological issues.
PMID- 28423230
TI - Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity
in lung cancer cells.
AB - Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell
proliferation and oncogenesis. Here, we report that GOF p53 induces
tumorigenicity through simultaneous activation of key oncogenic pathways
including those controlling putative tumor-initiating cell functions. We
determined that in cells expressing p53-R273H, GOF p53 simultaneously upregulates
genes from multiple signaling pathways by recognizing promoters containing
distinct transcription factor (TF) binding sites. Our analytical data support a
model in which GOF p53 complexes with two TFs on the promoter-a mediator protein,
Med17, and a histone acetyl transferase, activating histone acetylation-and
enhances gene expression to signal cell proliferation and oncogenesis. Thus,
therapeutic inhibition of one GOF p53-induced pathway would be insufficient to
prevent tumor growth as the oncoprotein activates a multitude of parallel
pathways. This discovery suggests enormous selection advantage for cancer cells
with GOF p53 to induce oncogenic growth, highlighting the problems of cancer
therapy.
PMID- 28423231
TI - Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence
rate in cirrhotic patients with chronic hepatitis C.
AB - BACKGROUND AND AIMS: Arrival of direct-acting antiviral agents against hepatitis
C virus with high-sustained virological response rates and very few side effects
has drastically changed the management of hepatitis C virus infection. The impact
of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after
a first remission in patients with advanced fibrosis remains to be clarified.
METHODS: 68 consecutive hepatitis C virus patients with a first hepatocellular
carcinoma diagnosis and under remission, subsequently treated or not with a
direct-acting antiviral combination, were included. Clinical, biological and
virological data were collected at first hepatocellular carcinoma diagnosis, at
remission and during the surveillance period. RESULTS: All patients were
cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three
patients (34%) were treated with direct-acting antivirals and 96% of them
achieved sustained virological response. Median time between hepatocellular
carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR:
3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start
and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range:
3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs
4.2/100 person-months among untreated patients (P=.008). In multivariate survival
analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct
acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; P<.001).
CONCLUSIONS: Hepatocellular carcinoma recurrence rate was significantly lower
among patients treated with direct-acting antivirals compared with untreated
patients. Given the potential impact of our observation, large-scale prospective
cohort studies are needed to confirm these results.
PMID- 28423232
TI - A psychometric evaluation of the anatomy learning experiences questionnaire and
correlations with learning outcomes.
AB - The Anatomy Learning Experiences Questionnaire (ALEQ) was designed by Smith and
Mathias to explore students' perceptions and experiences of learning anatomy. In
this study, the psychometric properties of a slightly altered 34-item ALEQ (ALEQ
34) were evaluated, and correlations with learning outcomes investigated, by
surveying first- and second-year undergraduate medical students; 181 usable
responses were obtained (75% response rate). Psychometric analysis demonstrated
overall good reliability (Cronbach's alpha of 0.85). Exploratory factor analysis
yielded a 27-item, three-factor solution (ALEQ-27, Cronbach's alpha of 0.86),
described as: (Factor 1) (Reversed) challenges in learning anatomy, (Factor 2)
Applications and importance of anatomy, and (Factor 3) Learning in the dissection
laboratory. Second-year students had somewhat greater challenges and less
positive attitudes in learning anatomy than first-year students. Females reported
slightly greater challenges and less confidence in learning anatomy than males.
Total scores on summative gross anatomy examination questions correlated with
ALEQ-27, Pearson's r = 0.222 and 0.271, in years 1 and 2, respectively, and with
Factor 1, r = 0.479 and 0.317 (all statistically significant). Factor 1 also had
similar correlations across different question types (multiple choice; short
answer or essay; cadaveric; and anatomical models, bones, or radiological
images). In a retrospective analysis, Factor 1 predicted poor end-of-semester
anatomy examination results in year 1 with a sensitivity of 88% and positive
predictive value of 33%. Further development of ALEQ-27 may enable deeper
understanding of students' learning of anatomy, and its ten-item Factor 1 may be
a useful screening tool to identify at-risk students. Anat Sci Educ 10: 514-527.
(c) 2017 American Association of Anatomists.
PMID- 28423233
TI - Ivabradine vs metoprolol in patients with acute inferior wall myocardial
infarction-"Expanding arena for ivabradine".
AB - BACKGROUND: Atrioventricular (AV) blocks are of concern with the use of beta
blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart
rate with a lesser risk of AV blocks. OBJECTIVES: To compare ivabradine with
metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and
efficacy. METHODS: It was a prospective double-blind single-center randomized
controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible
patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol
(group B). Intention to treat analysis of 426 patients (group A-232 and group B
232) was performed. The primary endpoint was 30-day incidence of major adverse
cardiovascular events including death, reinfarction, complete heart block (CHB),
and heart failure. Secondary endpoints included 30 days incidence of recurrent
angina, readmission, first- or second-degree AV block, and tachyarrhythmias.
RESULTS: Both the drugs decreased the mean heart rate to 62.22+/-2.95 (group A)
vs 62.53+/-3.59 (group B) beats per minute (P=0.33). Ejection fraction improved
in both the groups (5.15+/-1.93% in group A vs 5.52+/-2.18% in group B, P=0.065).
The two groups did not differ significantly in their primary endpoints in terms
of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00),
reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00),
heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75,
P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no
significant differences in the secondary endpoints of recurrent angina,
readmission, and tachyarrhythmias except for more first- and second-degree AV
blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002).
CONCLUSIONS: Ivabradine is well tolerated and equally effective as metoprolol in
acute inferior wall ST elevation myocardial infarction patients for lowering the
heart rate with lesser risk of AV blocks.
PMID- 28423234
TI - Pulmonary vein isolation with concomitant renal artery denervation is associated
with reduction in both arterial blood pressure and atrial fibrillation burden:
Data from implantable cardiac monitor.
AB - BACKGROUND: Renal artery denervation (RDN) has provided incremental atrial
fibrillation (AF) suppression after pulmonary vein isolation (PVI) in patients
with AF in the setting of drug-resistant hypertension. OBJECTIVE: To assess the
relationship between changes of mean blood pressure (BP) and AF recurrences/AF
burden after PVI combined with RDN. METHODS: All patients from two randomized
studies with symptomatic paroxysmal AF and/or persistent AF and resistant
hypertension who underwent PVI-only (n=37) or PVI with RDN (n=39), and
implantable cardiac monitor (ICM) implantation were eligible for this study.
Mixed-effects linear models were used to investigate the effect of RDN on mean BP
and mean AF burden and associations between the two during the 12-month follow
up. RESULTS: Concomitant RDN was associated with a significant reduction in both
mean AF burden (2.43 [95% CI: 1.76-3.09] % vs 6.95 [95% CI: 5.44-8.45] %) and
mean BP (104 [95% CI: 103-106] mm Hg vs 112 [95% CI: 110-113] mm Hg). Decrease in
mean BP was positively correlated with decline in mean AF burden: reduction of 5
10 mm Hg was accompanied by a 7.0% decreased mean AF burden, with greater
reduction (up to 20 mm Hg) associated with on average 17.7% lower mean AF burden.
CONCLUSIONS: Renal artery denervation when added to PVI decreases AF recurrences,
AF burden, and mean BP. Reduction in mean BP is associated with both AF burden
and recurrences. Further large-scale studies are needed to define the mechanistic
pathway(s) of the antiarrhythmic effects of RDN.
PMID- 28423235
TI - Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood
acute lymphoblastic leukemia is associated with continuous asparaginase therapy
and mercaptopurine metabolites.
AB - BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of
childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6
thioguanine. The occurrence of several SOS cases after the introduction of
extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society
of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to
hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS
during 6-thioguanine-free maintenance therapy. PROCEDURE: In children with ALL
treated in Denmark according to the NOPHO ALL2008 protocol, we investigated the
risk of SOS during methotrexate (MTX)/6-mercaptopurine (6MP) maintenance therapy
that included PEG-asparaginase until week 33 (randomized to two- vs. six-week
intervals), as well as alternating high-dose MTX or vincristine/dexamethasone
pulses every four weeks. RESULTS: Among 130 children receiving PEG-asparaginase
biweekly, 29 developed SOS (>=2 criteria: hyperbilirubinemia, hepatomegaly,
ascites, weight gain >=2.5%, unexplained thrombocytopenia <75 * 109 l-1 ) at a
median of 30 days (interquartile range [IQR]: 17-66) into maintenance (cumulative
incidence: 27%). SOS cases fulfilling one, two, or three Ponte di Legno criteria
were classified as possible (n = 2), probable (n = 8), or verified (n = 19) SOS,
respectively. Twenty-six cases (90%) occurred during PEG-asparaginase treatment,
including 21 (81%) within 14 days from the last chemotherapy pulse compared with
the subsequent 14 days (P = 0.0025). Cytotoxic 6MP metabolites were significantly
higher on PEG-asparaginase compared to after its discontinuation. Time-dependent
Cox regression analysis showed increased SOS hazard ratio (HR) for erythrocyte
levels of methylated 6MP metabolites (HR: 1.09 per 1,000 nmol/mmol hemoglobin
increase, 95% confidence interval: 1.05-1.14). Six-week PEG-asparaginase
intervals significantly reduced SOS-specific hazards (P < 0.01). CONCLUSIONS: PEG
asparaginase increases cytotoxic 6MP metabolite levels and risk of SOS,
potentially interacting with other chemotherapy pulses.
PMID- 28423236
TI - Improvement in treatment abandonment in pediatric patients with cancer in
Guatemala.
AB - BACKGROUND: Treatment refusal and abandonment are major causes of treatment
failure for children with cancer in low- and middle-income countries (LMICs),
like Guatemala. This study identified risk factors for and described the
intervention that decreased abandonment. METHODS: This was a retrospective study
of Guatemalan children (0-18 years) with cancer treated at the Unidad Nacional de
Oncologia Pediatrica (UNOP), 2001-2008, using the Pediatric Oncology Network
Database. Treatment refusal was a failure to begin treatment and treatment
abandonment was a lapse of 4 weeks or longer in treatment. The impact of medicina
integral, a multidisciplinary psychosocial intervention team at UNOP was
evaluated. Cox proportional hazards analysis identified the effect of demographic
and clinical factors on abandonment. Kaplan-Meier analysis estimated the
survival. RESULTS: Of 1,789 patients, 21% refused or abandoned treatment.
Abandonment decreased from 27% in 2001 to 7% in 2008 following the implementation
of medicina integral. Factors associated with increased risk of refusal and
abandonment: greater distance to the centre (P < 0.001), younger age (P = 0.017)
and earlier year of diagnosis (P < 0.001). Indigenous race/ethnicity (P = 0.002)
was associated with increased risk of abandonment alone. Abandonment correlated
with decreased overall survival: 0.57 +/- 0.02 (survival +/- standard error) for
those who completed therapy versus 0.06 +/- 0.02 for those who abandoned
treatment (P < 0.001) at 8.3 years. CONCLUSION: This study identified distance,
age, year of diagnosis and indigenous race/ethnicity as risk factors for
abandonment. A multidisciplinary intervention reduced abandonment and can be
replicated in other LMICs.
PMID- 28423237
TI - Assessment of vascular response to BiOSS LIM C(r) stents vs Orsiro(r) stents in
the porcine coronary artery model.
AB - AIMS: The optimal treatment strategy for coronary bifurcation lesions is still
unknown. The aim of the study was to assess applicability of the new cobalt
chromium version of the sirolimus-eluting dedicated bifurcation BiOSS(r) LIM C
stent in comparison with regular sirolimus-eluting Orsiro(r) stent in a porcine
coronary model. METHODS: A total of 13 BiOSS(r) LIM C stents and 6 Orsiro(r)
stents were implanted in normal nonatherosclerotic porcine straight coronary
arteries of six animals using 1.2:1.0 stent-to-artery ratio. Stent geometry and
morphology were evaluated by Faxitron imaging. Vascular response was assessed by
quantitative coronary angiography (QCA), optical coherence tomography (OCT), and
histological analyses. RESULTS: OCT performed at 28 days confirmed that all
stents were patent with no signs of thrombus. In morphometric analysis, no
differences between groups regarding stent diameter (P=.141), neointima area
(P=.247), % area stenosis (P=.293), or % diameter stenosis (P=.069) were
observed. Also, no significant differences were noted between groups regarding
their histopathology scores. The injury and inflammation scores were low (mean
grade<1) in all groups. CONCLUSIONS: The novel BiOSS(r) LIM C stent demonstrates
good short-term vascular effects in a porcine coronary bifurcation model which
are comparable with Orsiro(r) stents.
PMID- 28423238
TI - Higher plasma leptin is associated with higher risk of androgenetic alopecia in
men.
AB - In addition to genetics and androgens, novel factors could play a role in
androgenetic alopecia (AGA). This study aims to investigate the association
between plasma leptin level with the risk and severity of AGA in men. Forty-eight
subjects were enrolled including 29 AGA and 19 non-AGA subjects. The plasma
leptin level was significantly higher in AGA subjects, compared to non-AGA
subjects (4.45 vs 2.76 ng/mL, P<.05). A higher plasma leptin levels were
positively correlated with the risk of developing AGA in multivariate logistic
analysis (odds ratio=2.77, P<.05). Leptin from the circulation might impact the
development of AGA.
PMID- 28423239
TI - A novel JAK inhibitor JTE-052 reduces skin inflammation and ameliorates chronic
dermatitis in rodent models: Comparison with conventional therapeutic agents.
AB - Janus kinases (JAKs) are required for several inflammatory cytokine signalling
pathways and are implicated in the pathogenesis of chronic dermatitis, including
atopic dermatitis and psoriasis. JAK inhibitors are therefore promising
therapeutic candidates for chronic dermatitis. In this study, we evaluated the
effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated
with chronic dermatitis, and compared its profile with those of conventional
therapeutic agents in rodent models of chronic dermatitis. JTE-052 inhibited the
Th1-, Th2- and Th17-type inflammatory responses of human T cells and mast cells
in vitro. Oral administration of JTE-052 inhibited skin inflammation in hapten
induced chronic dermatitis in mice, associated with reduced levels of
inflammatory cytokines in the skin and immunoglobulin (Ig) E in serum. In
contrast, although ciclosporin partly inhibited skin inflammation, it did not
reduce interleukin (IL)-4 production in skin, and enhanced IgE production in
serum. Oral administration of JTE-052 also inhibited skin inflammation in mouse
models of atopic dermatitis and psoriasis induced by a mite extract, thymic
stromal lymphopoietin or IL-23. The maximal efficacy of JTE-052 in these
dermatitis models was superior to the conventional therapeutic agents,
ciclosporin and methotrexate. Topical application of JTE-052 ointment ameliorated
hapten-induced chronic dermatitis in rats more effectively than tacrolimus
ointment. Furthermore, JTE-052 ointment did not cause the thinning of normal skin
associated with topical corticosteroids. These results indicate that JTE-052 is a
promising candidate as an anti-inflammatory drug for various types of chronic
dermatitis, with a distinctly different profile from conventional therapy
following either oral or topical application.
PMID- 28423240
TI - Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss
of N-Glycolylneuraminic Acid.
AB - About 2-3 million years ago, Alu-mediated deletion of a critical exon in the CMAH
gene became fixed in the hominin lineage ancestral to humans, possibly through a
stepwise process of selection by pathogen targeting of the CMAH product (the
sialic acid Neu5Gc), followed by reproductive isolation through female anti
Neu5Gc antibodies. Loss of CMAH has occurred independently in some other
lineages, but is functionally intact in Old World primates, including our closest
relatives, the chimpanzee. Although the biophysical and biochemical ramifications
of losing tens of millions of Neu5Gc hydroxy groups at most cell surfaces remains
poorly understood, we do know that there are multiscale effects functionally
relevant to both sides of the host-pathogen interface. Hominin CMAH loss might
also contribute to understanding human evolution, at the time when our ancestors
were starting to use stone tools, increasing their consumption of meat, and
possibly hunting. Comparisons with chimpanzees within ethical and practical
limitations have revealed some consequences of human CMAH loss, but more has been
learned by using a mouse model with a human-like Cmah inactivation. For example,
such mice can develop antibodies against Neu5Gc that could affect inflammatory
processes like cancer progression in the face of Neu5Gc metabolic incorporation
from red meats, display a hyper-reactive immune system, a human-like tendency for
delayed wound healing, late-onset hearing loss, insulin resistance,
susceptibility to muscular dystrophy pathologies, and increased sensitivity to
multiple human-adapted pathogens involving sialic acids. Further studies in such
mice could provide a model for other human-specific processes and pathologies
involving sialic acid biology that have yet to be explored.
PMID- 28423241
TI - [The reasons for the "space" of gerontology: the impact of the movements of the
Earth and Moon on the performance of the human environment].
AB - For future gerontological research specific interest are the research results
obtained at the junction of Geophysics, astronomy, and biology, and existing
links pointing to indicators of living objects with cosmophysical factors. The
paper presents data on basic astronomical factors, potentially on a regular basis
may cause gravitational effects on the biosphere as a living environment. Among
these factors are movement of the Earth and Moon described is known in astronomy
equations: the equation of the equinoxes, equation of time, as well as major
perturbations from the Sun (evection, variation and annual inequality) inferred
from the theory of lunar motion. Based on the amount of major perturbations from
the Sun, the so-called lambdaD-functions that are carried out to study the
relationship between fluctuations of the so-called "computer time", the energy of
solar radiation in the range of 605-607 nm, and the concentration of hemoglobin
and red blood cells with major perturbations from the Sun. The resulting
conclusion about the universal nature of the impact of the movements of the Moon
and the Earth on the biosphere. The tables for the period from 01.01.2015 to
31.12.2016, with the calculated values lambdaD functions that are potentially
important for analyzing their association with temporal changes of various
indicators of the body. The regularities obtained in the comparison of changes in
various biomarkers with the course of values lambdaD functions from tables, can
be predictive in the study of the functioning of humans and the biosphere for
astronomical periods. The research was carried out in Antarctica, where excluded
the influence of artificial electromagnetic fields, st. Vostok (1998-1999) and
st. Novolazarevskaya (2003-2004).
PMID- 28423242
TI - [The gravity field of the Earth: geophysical factor of gerontology (The
Vorobeichikov effect)].
AB - The results of investigations of the growth in vitro of Escherichia coli M-17,
obtained in the processing of V. M. Vorobeichikov observational data during the
movement of the scientific expedition ship "Akademik Fedorov" from St. Petersburg
to Antarctica and back, in the period from 13.11.2002 on 26.05.2003 (48th Russian
Antarctic expedition). The findings based on the growth in vitro of Escherichia
coli from changes in geographical location on a planetary scale, that doesn't
eliminate the dependence of other species of microorganisms from the spatial
position in the gravity field of the Earth. It is established that the duration
of the lag phase of Escherichia coli in the Equatorial zone close to its duration
in the high-latitude zone and Antarctic, however, the duration of the lag phase
at the equator and the Antarctic corresponds to the time of the lag phase at the
time of the Central phase of the lunar Eclipse. The conclusion about high
sensitivity in vitro of Escherichia coli to the field of gravity of the Earth,
and to syzigium events.
PMID- 28423243
TI - [Role of circadian rhythms and cellular clock in aging cancer development].
AB - Almost all the body's functions exhibit circadian rhythm maintained in a cell by
a system of Clock genes and proteins. Failure to synchronize or loss of these
rhythms are found in aged organism and are associated with risk of cancer
development. The article describes data on mechanisms of circadian rhythms
regulation in whole organism and cell, rhythm change during aging and
relationship between rhythm disturbances and tumorigenesis of different
localisations in humans and animals.
PMID- 28423244
TI - [Discontinuity of the annuity curves. II. Variability of annuity curves in
Drosophila melanogaster Canton S strain].
AB - We analyzed "five phase" structure of Drosophila melanogaster annuity curves
described earlier. It did not depend on the sample size and seemed to be stable.
We argue that: 1. there must be strict determination of "five phase" structure;
2. variability of its duration, may be induced by weak unknown signals.
PMID- 28423245
TI - [Shaotic dynamics of cardio-intervals in three age groups of indigenous and non
indigenous population of Ugra].
AB - The problem of life expectancy of indigenous and non-indigenous population of
northern territories of the Russian Federation is considered in terms of economic
growth and industrial development of the northern territories. The importance of
prolonging the period of active working age of non-indigenous population of
Khanty-Mansi Autonomous Okrug-Ugra and Yamalo-Nenets Autonomous Okrug is
increasing. Four directions for possible prolongation of the active life of non
indigenous population were presented. The problem of comparative dynamics of age
related changes of cardiovascular system on three specific age groups of female
indigenous and non-indigenous population is being considered. A decrease in
volume of quasi-attractors in the phase space of states is equivalent to
strengthening of physical activity, which is typical of normal aging. It is
proposed to use the mathematical pattern to reduce these volumes in assessing the
dynamics of human aging in the North.
PMID- 28423246
TI - [PROINFLAMMATORY CYTOKINE GENE POLYMORPHISMS AND THE PLASMA AND SYNOVIAL FLUID
LEVELS OF CYTOKINES IN PATIENTS WITH POST-TRAUMATIC KNEE OSTEOARTHRITIS].
AB - Post-traumatic knee osteoarthritis patients (n=117) and healthy people (n=94)
were investigated to determine the genotypic and allelic frequency distribution
of polymorphic loci T-31S, S+3953T IL-1beta and G-308A TNF-alpha. The plasma and
synovial fluid levels of proinflammatory cytokines IL-1beta and TNF-alpha were
measured in 31 patients. The research demonstrated that the blood and synovial
fluid levels of IL-1beta but not TNF-alpha were increased in patients with post
traumatic knee osteoarthritis. Also, the linkage between TNF-alpha level and
polymorphic locus G-308A TNF-alpha was shown: the presence of allele -308A was
associated with decreased TNF-alpha level. We demonstrated that polymorphic loci
T-31S, S+3953T IL-1beta and G-308A TNF-alpha do not predict the higher risk of
post-traumatic knee osteoarthritis development in Russian population of Rostov-on
Don region.
PMID- 28423247
TI - [COMPARATIVE MORPHOFUNCTIONAL CHARACTERISTICS OF ADULT AND OLD RAT VENTRAL
HIPPOCAMPUS TO COMBINED STRESS INFLUENCE].
AB - Animals were subjected to seven days combined stress in a special chamber (6
isolated compartments of equal area) with removable multi-modal stressors (noise,
vibration, pulsating bright light) every 5 minutes on the stochastic scheme with
restraint and temperature rise in the chamber during 30-minute stressing time
sessions. After exposure to combined stress in the ventral hippocampus of old
rats (24 months) compared with adult animals (12 months) following changes were
revealed: marked dystrophic changes and increased inducible nitric oxide synthase
expression in pyramidal neurons of CA3 field, signs of impaired hemodynamic
disorders in the microvasculature, perivascular edema, decreased endothelial
nitric oxide synthase expression in microvascular endothelial cells, as well as
decreased expression of serine racemase in the neuropil of the radial layer of
CA1 field.
PMID- 28423248
TI - [Disulfiram inhibites the development of cataract in OXYS rats].
AB - Surgical treatment remains the only way to restore vision in patients with
cataract; this disorder is the most common reason for vision decline and vision
loss in people older than 65 years. It is estimated that a 10-year delay in the
development of cataract will reduce the need for surgery twofold. In 2012, Nagai
and colleagues reported an anticataract effect of an inhibitor of acetaldehyde
dehydrogenase-a widely used antialcoholism drug disulfiram (DSF) - in ICR/f rats
with hereditary cataracts. Accordingly, the goal of the present study was to
evaluate the influence of DSF on the cataract in OXYS rats, which develop lens
alterations similar to senile cataract in humans. Instillation of DSF from age
1,5 to 3,5 months did not prevent but significantly slowed the development of
cataracts in OXYS rats. At concentrations of 0,25 % and 0,5 %, DSF reduced the
severity of pathological changes in the lens 1,8-fold and was more effective than
at the concentration 1 %. These data were consistent with the results of
ophthalmoscopic histomorphological examination: the pharmacotherapy strongly
reduced the (typical of cataract) structural damage to the capsule of the lens
epithelium and to organization of its fibers. Thus, disulfiram is a promising
drug for the prevention of senile cataract in humans.
PMID- 28423249
TI - [The investigation of blood cells of middle and old age in patients with
bronchial asthma and chronic obstructive pulmonary disease by atomic force
microscopy. Similarities and differences with the biological animal model].
AB - The investigation of reactive changes of blood cells in such diseases as COPD or
asthma in people of different age groups is the very difficult problem.
Simulating the same conditions in animals that occur in humans with these
diseases can serve as a reliable practical model. It is possible because the
changes which take places at the cellular level in animals might reflect a
similar trend in the human body.
PMID- 28423250
TI - [Association of renal function, telomere length and markers of chronic
inflammation for patients without chronic kidney and cardiovascular diseases].
AB - : Most of people over 60 years of age have decreased renal function and the
velocity of glomerular filtration rate reduction varies greatly. Presumably, one
of the probable mechanisms of accelerated decline of renal function may be a
shortening of telomere length due to chronic inflammation. The main purpose of
research was to appreciate the association of renal function, leukocytes
telomeres length and markers of chronic inflammation in patients without chronic
kidney disease and cardiovascular disease. 253 patients without chronic kidney
diseases and cardiovascular diseases were included in the study. The average age
of patients was 51,5+/-13,3 years. There were 172 women and 81 men. 55 patients
had hypertension of 1-2 degree, 46 patients had normal renal function, 207 had
mild failure of kidney function. Albuminuria was < 30 mg/day in all patients.
Multivariate linear regression analysis revealed statistically significant
correlation between albuminuria level and telomere length (p=0,023), C reactive
protein (p=0,047) and fibrinogen (p=0,001). Glomerular filtration rate, urea and
creatinine were not associated with telomere length and markers of inflammation
but were correlated well with age, p < 0,001. CONCLUSIONS: Albuminuria is mainly
associated with chronic inflammation and telomere length (from all studied
indices of renal function). Albuminuria may be regarded as a marker of
replicative cell senescence and a therapeutic target for the prevention of renal
function reduction.
PMID- 28423252
TI - [THE CHOICE OF SURGICAL TREATMENT OF OBSTRUCTIVE ILEUS IN ELDERLY AND SENILE
PATIENTS].
AB - The article presents results of treatment of 100 patients with elderly colon
cancer complicated by obstructive ileus. Patients were divided into two groups of
50 people. Main group patients for colon surgery performed using laparoscopic
techniques. The efficiency of operations on the colon laparoscopically - fewer
postoperative complications, length of postoperative hospital stay days. Deaths
in the study group was not (control - 6 %).
PMID- 28423251
TI - [ASSOCIATION OF AGE OBESITY AND METABOLIC SYNDROME IN MEN].
AB - The study included 253 men aged 22 to 74 years. Was shown that at the end of the
first period of middle age the accumulation of adipose tissue was enhanced that
was associated with the change of dominance from the gynoid to the android type
of obesity. The most pronounced increase in the frequency of occurrence of
individual components and the overall metabolic syndrome was diagnosed in men in
the second period of middle age with a following decrease in the frequency such
components as hypertriglyceridemia, low HDL cholesterol and hyperglycemia in
elderly age. In the all three age groups the value of the index of visceral
obesity was significantly higher in men with android type of obesity compared
with gynoid. Thus, the men with gynoid compared with android type of obesity have
a lower risk of development metabolic syndrome in all age groups.
PMID- 28423253
TI - [Association of renal function, telomere length and markers of chronic
inflammation for patients without chronic kidney and cardiovascular diseases].
AB - The retrospective analysis of 50 cases of acute myocardial infarction's treatment
in patients older than 90 years old was held. Patients' age ranged from 90 to 101
years old. The average age was 92,1+/-0,7 years. 20 (40 %) patients have had
reperfusion therapy: thrombolytic therapy - 2 (4 %), emergency coronary stenting
18 (36%). The mortality rate was 26 %. Mortality in groups with/without
reperfusion therapy was 20 % and 30 %, respectively. In the subgroup of coronary
stenting, 4 patients died (the mortality rate was 22,2 %). The specialized
medical care for patients over 90 years old with acute myocardial infarction
associated with high mortality (26 %). It was proved statistically that the
reduction (p < 0,05) of mortality is connected with coronary stenting. In cases
with endovascular technical possibilities' presence, even with multivessel
lesions, it is necessary to perform coronary stenting of the infarct/ischemia
responsible coronary artery. It is particularly important in cases complicated by
acute heart failure.
PMID- 28423254
TI - [Optimization of treatment of elderly patientswith diabetic foot syndrome and
mediakaltsinozom arteries].
AB - The objective of the research was to study the effectiveness of the drug
Cytoflavin in the comprehensive treatment of mixed form diabetic foot syndrome
with media calcification arteries in 75 elderly patients with type 2 diabetes.
Depending on the regimen, patients were divided into two groups: control received
basic therapy; main group in addition to the base, received the drug Cytoflavin
10 ml 0,9 % NaCl 200 ml for 10 days, followed by a transition to the tablet form
of the drug - 2 tablets 2 times per day orally for one month. The inclusion of
the drug Cytoflavin in the treatment regimen increased the effectiveness of
treatment, which was shown to improve tissue oxygenation due to the normalization
of the basal oxygen tension, restoring the activity of antioxidant enzymes and,
consequently, in an authentic decrease in the average time of hospital treatment
and a decrease in the number of repeated surgical interventions and reamputatsy
over the next year.
PMID- 28423255
TI - [AGED CARDIOHEMODYNAMICS COMPLICATED BY STROKE].
AB - A new method of arterial piezopulsometry allowed a 12-year study of the
peculiarities of age-related changes in cardiac hemodynamic indices in an aged
man after ischemic stroke. The ob-tained results enable use of these indicators
as prognostic criteria of an individual organism's re-sistance to acceleration
factors of aging, as well as its resistance to the development of the cardi
ovascular pathology caused by the stroke. Simultaneous dual registration of
piezopulsograms al-lowed establishing a significant increase of the augmentation
index of pulse pressure (AIxPP) and the velocity of the pulse wave of blood
pressure propagation through the radial artery (Var) in a paralyzed right arm,
compared to the left hand control (p < 0,05). Range fluctuations in the relative
values of this difference can serve as an objective indicator of the functional
state of a paralyzed arm of a patient during rehabilitation treatment, and a
sharp decrease of this difference and its subsequent stabilization can serve as
an indicator of the beginning of recovery.
PMID- 28423256
TI - [Cardioprotective effect of the new derivative of glutamic acid - glufimet in
acute immobilization-painful stress in animals of different ages].
AB - The effect of the 24-hour immobilization-painful stress on myocardial
contractility of young (6-month), middle-aged (12-month) and old (24-month)
female rats was studied. It was identified a reduction of the functional reserve
of the heart, which showed a smaller growth rates of contraction and relaxation
of the myocardium (+ dP/dt max and -dP/dt max), left ventricular pressure (LVP)
and the maximum intensity of the functioning of the structures (MIFS) under
increased pre- afterload and adrenergic stimulation of the heart, especially
pronounced in the group of 24-month old rats. The animals of all ages treated
before and after stressing glufimet in a dose 29 mg/kg, have higher rates of
growth + dP/dt max, -dP/dt max, LVP and MIFS during load tests, most significant
rates of growth are noticed in older rats compared with the young and middle
aged. Phenibut improves studied parameters equally at 6, 12 and 24-month old
females, subjected to stress.
PMID- 28423257
TI - [Acute myocardial infarction in elderly and senile patients: epidemiology study
according to the who program "registry of acute myocardial infarction].
AB - The article presents results of the epidemiology study of acute myocardial
infarction (AMI) among permanent Tomsk residents older than 60 years. The study
was conducted in 2008-2009 according to the WHO program "Registry of Acute
Myocardial Infarction". Data demonstrated that morbidity and mortality from AMI
was higher in the above mentioned age group than in younger population. Rates of
morbidity and mortality in men exceeded those in women in all age groups except
population older than 80 years. The study showed high in-hospital lethality
caused by high death rates in patients 60 years of age and older who were treated
in non-specialized hospitals. Authors conclude that the severity of epidemiology
situation with AMI is determined by the frequency of this pathology in population
older than 60 years suggesting the necessity of change in the strategy of system
development of medical care for AMI patients with focus on the older age groups.
PMID- 28423258
TI - [OPTIMIZATION OF REPARATIVE OSTEOGENESIS JAWS ON AGING (PRECLINICAL STUDIES)].
AB - The article presents the results of pre-clinical studies of the possibility of
optimization of reparative osteogenesis in postoperative bone cavities of the
jaws in old rats with a peptide bioregulator of Kartalaks. Using histological and
morphometric methods in the experimental study, it is shown that the use of
Kartalaks positive effect on the course of the process of reparative osteogenesis
of the mandible in old rats. The features of the Kartalaks drug investigated for
optimization of reparative osteogenesis jaw during aging. It is found that by
using Kartalaks in old animals to 30 days before the surgical intervention, the
process of reparative osteogenesis standard defect of mandible occurs at early
stages (before 30 days), similar to the control. The deadlines for 60-120 days
from the beginning of the experiment using the peptide bioregulator Kartalaks,
noted the formation of a complex regenerate tissue containing a smaller
proportion of connective tissue and cartilage, as well as more advanced
remodeling of newly formed bone tissue compared with the control group, and older
animals who received the drug after performing surgery.
PMID- 28423259
TI - [Attitudes to elderly people in everyday life: Attitudes to elderly people in
everyday life: conceptual outlines of explanation model].
AB - The article deals with problems related to the third age in contemporary Russia.
It is based on empirical data obtained in unstructured students interviews (N=53)
in Saratov and Moscow in 2007-2014. The author shows that the lack of a
respectful behavior regardless its reasons is often labeled as "disrespect". As a
result a "neutral attitude" is devoid of practical implementation. In reality a
"good attitude" to the third age is often unrealized because of the actions of
older people themselves, as these actions are incompatible with respect
practices. These asymmetrical actions are embodied in intergenerational contacts
and may take form of non-status behavior that disqualifies an elder actor as a
potential object of respect, etc.
PMID- 28423260
TI - [DIAGNOSIS OF EMOTIONAL SPHERE DISORDERS IN ELDERLY].
AB - The article describes the structure of criteria of severity and recommendations
for the diagnosis of emotional sphere disorders in elderly. An algorithm for
diagnosis of emotional sphere is described, which includes four phases: screening
and diagnostic, clinical and patho-psychological, laboratory and instrumental
diagnostic, psycho-diagnostic; it can be applied as to estimate the prevalence of
various forms of emotional disorders, and for their early correction and
prevention at the individual level. The criteria of anxiety expression evaluation
and asthenic disorders are presented. The recommendations can be used in the
activities of somatic practices doctors (therapist, general practitioners,
neurologists).
PMID- 28423261
TI - [Comparative characteristics of depressive tendencies in patients with
tuberculosis and chronic obstructive pulmonary disease].
AB - Chronic obstructive pulmonary disease (COPD) and tuberculosis are socially
significant diseases that can develop at any age, and require long-term,
sometimes lifelong, therapy. Diseases will inevitably cause a deficiency of
oxygen in the body that can cause disorders of the nervous system, from the mood
changes to reduce intelligence, especially in the elderly. According to the
results of the study the majority of patients with COPD and a third of patients
with tuberculosis, there are significant problems of the emotional plane,
especially in older and elderly expressed in the presence of depressive
tendencies (from subdepressive states to real depression), and almost half of the
patients in need of specially organized psychological or medical assistance.
PMID- 28423262
TI - [sRAGE LEVEL AND ITS ASSOCIATION WITH COGNITIVE STATUS OF PATIENTS WITH
ALZHEIMER'S DISEASE AND MIXED VASCULAR-DEGENERATIVE COGNITIVE IMPAIRMENT].
AB - The differences in level of soluble forms of receptor for advanced glycation end
products (sRAGE) in the blood serum of patients with Alzheimer's disease and
mixed vascular-degenerative cognitive impairment were studied. sRAGE in blood
serum of the patients with Alzheimer's disease is lower than that in patients
with mixed vascular-degenerative cognitive impairments. Correlation analysis of
serum sRAGE level and indicators of cognitive status was performed. Low level of
sRAGE is associated with worse memory that is typical for Alzheimer's
neurodegenerative process. This fact confirms the pathogenetic significance of
the studied biomarker.
PMID- 28423263
TI - [EXPERIENCE WITH THE USE OF EPTIFIBATIDE IN ACUTE CORONARY SYNDROME DURING
CORONARY INTERVENTION IN PATIENTS OLDER AGE GROUP].
AB - Acute coronary syndrome is the leading cause of death in patients older age
group. Primary PCI is nearly uncontested revascularization method because of its
efficacy in reperfusion achievement and less hemorrhagic complications compared
to systemic thrombolytic therapy. Nevertheless, the age of the patients is a
significant bleeding risk factor, sophisticating the choice and dosing
antiplatelet and anticoagulant therapy during coronary angioplasty and stenting.
Blocker 2b/3a receptor eptifibatide are used to avoids the development of
ischemic complications and improves myocardial perfusion, but accompanied with
bleeding risk during common infusion (12-18 hours). Combined intracoronary and
intravenous infusion eptifibatide during only coronary intervention enhance
procedure safety.
PMID- 28423264
TI - [INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH AS A MODERN
TOOL FOR ASSESSING QUALITY REHABILITATION OF PATIENTS].
AB - The article used the methods of assessment of knee function, structure and
functional activity in elderly patients with osteoarthritis to represent in terms
of the ICF structure and subsequent evaluation of the rehabilitation patient
profile and effectiveness of medical rehabilitation of patients with
osteoarthritis of the knee. It is shown that the inclusion in the program of
rehabilitation of older patients with osteoarthritis of the knee EHF-IR therapy
provides a more pronounced clinical effect. An analysis of the profile of the
rehabilitation of patients shows positive dynamics of all three components of the
assessment of the rehabilitated patients (function, structure, activity). The
data confirm the possibility of using the ICF in its use as a criterion for the
scientific evaluation of the effectiveness of rehabilitation of patients with
osteoarthritis.
PMID- 28423265
TI - [ADVANCED AND SENILE AGE FOR THE FIRST DAYS AFTER X-RAY ENDOVASCULAR
INTERVENTIONS].
AB - Research of the glomerular filtration rate at the patients of advanced and senile
age who underwent X ray endovascular intervention is conducted. Patients of age
groups are examined: 34-59 years (49,7+/-7,8 years) - 35 people (group of
control), 60-74 years (65,5+/-4,1) - 38 people and 75-82 years (77,5+/-2,5) - 12
people. Methods of screening calculation of the glomerular filtration rate are
compared. The conclusion that regardless of techniques of definition of GFR and
its initial level, the orientation of change of this parameter is characterized
by its decrease at all patients after performance of coronary angiography, but
more at patients of senile age group is drawn. It is expedient to use Cockcroft
Gault's formula for screening determination of speed of the glomerular filtration
rate at people of advanced and senile age, in particular in patients with
ischemic heart disease when carrying out X-ray endovascular interventions.
PMID- 28423266
TI - [THE DYNAMICS AND STRUCTURE OF INDICATORS OF SECONDARY DISABILITY DUE TO
CEREBROVASCULAR DISEASES IN THE ELDERLY IN ST. PETERSBURG IN THE PERIOD 2005
2014].
AB - The article presents data about secondary disability due to cerebrovascular
diseases in the elderly based on results of examination in the Bureau of medical
social expertise of Saint Petersburg in the period from 2005 to 2014. The
analysis revealed a high proportion of the disabled elderly in the structure of
disability due cerebrovascular diseases; and the growth of the share of people
with disabilities elderly in the analyzed period.
PMID- 28423267
TI - [EMPLOYMENT OF THE ELDERLY PEOPLE IN THE EUROPEAN UNION AND UKRAINE: REALITIES,
PROBLEMS AND PROSPECTS].
AB - The study focuses on the issue of older people employment in the European Union
and Ukraine. We analyzed the relationship of employment for older people and
their income, of employment and of the value of index of social capital, life
expectancy and income after retirement. It is shown that the employment rate of
older people increased even during the economic crisis. The author has outlined
the main causes of employment and the fields of activity of retirees. The basic
reasons of employment are financial motives. However, motivation does not come
from financial necessity, but because of work satisfaction in countries such as
Denmark, Austria, Sweden. The main scope of employment of retirees in Ukraine is
the industrial sector, but in the EU working retirees 65+ are engaged in
agriculture, forestry and fishing sector, self-employment widespread among
retirees. The author has outlined the basic directions of pension policy.
PMID- 28423268
TI - [ROLE alpha2-ADRENERGIC RECEPTORS IN REGULATION PLATELET REACTIVITY IN THE
ELDERLY AT CHRONIC OBSTRUCTIVE PYELONEPHRITIS].
AB - Objective of the research was to determine involvement of platelets and the role
of adrenaline in chronic inflammation maintaining and the initiation of acute
inflammatory response in elderly patients with chronic obstructive pyelonephritis
against this background. The study includes 60 patients with chronic obstructive
pyelonephritis (COPN), which are distributed into two groups: basic - 22 elderly
patients (age 73+/-1,5 years) and the comparison group - 38 middle-aged patients
(52,5+/-2,4 years). The study excluded patients who took antiplatelet drugs and
non-selective blockers of alpha adrenergic receptors at least 1 week before the
study. Analysis of platelets adrenoreactivity in vitro was carried out at the
time of hospitalization before the start of conservative therapy. Platelet-rich
plasma was isolated from peripheral blood by centrifuging. ADP and epinephrine
were used in the effective (EC50) and sub-threshold (EC10) concentrations to
stimulate platelets. The formation of platelet-leukocyte aggregates was
reproduced in vitro upon incubation of stimulated platelets (at a concentration
of adrenaline EC50) and intact leukocytes isolated from patient peripheral blood.
The study of platelet reactivity revealed that in elderly patients acute
inflammatory response realization (relapse of COPN) is against optimal
functioning of platelets alpha2 adrenergic receptors. Significant increase in the
number of platelet-leukocyte aggregates is possible. Remission of COPN (the
presence of chronic inflammation) in the examined patients of various ages was
associated with platelet hypoadrenoreactivity. Increased platelet
adrenoreactivity during transition from remission to relapse of COPN in the
elderly patients is possible if adequate synthesis of ADP in platelets and its
secretion from dense granules are preserved. The observed interaction of
adrenaline and ADP with stimulated platelet hyporesponsiveness probably ensures
adaptive response aimed at acute inflammatory response in COPN.
PMID- 28423269
TI - Sensing by Smell: Nanoparticle-Enzyme Sensors for Rapid and Sensitive Detection
of Bacteria with Olfactory Output.
AB - We present here a highly efficient sensor for bacteria that provides an olfactory
output, allowing detection without the use of instrumentation and with a modality
that does not require visual identification. The sensor platform uses
nanoparticles to reversibly complex and inhibits lipase. These complexes are
disrupted in the presence of bacteria, restoring enzyme activity and generating
scent from odorless pro-fragrance substrate molecules. This system provides rapid
(15 min) sensing and very high sensitivity (102 cfu/mL) detection of bacteria
using the human sense of smell as an output.
PMID- 28423270
TI - Bioaccumulation and Biodistribution of Selenium in Metamorphosing Tadpoles.
AB - Selenium is an important macronutrient with a very narrow margin between
essentiality and toxicity. Amphibians are hypothesized to be particularly
sensitive due to the potential for metamorphosis-driven mobilization, which could
transfer or concentrate contaminant burdens within specific organs. We explored
the potential role of tissue degeneration and remodeling during anuran
metamorphosis as a mechanism for altering tissue-specific Se burdens.
Limnodynastes peronii tadpoles were exposed to dissolved 75Se (as selenite) for 7
days and depurated until completion of metamorphosis. Bioaccumulation and
retention kinetics were assessed in whole tadpoles and excised tissues using
gamma spectroscopy, and temporal changes in biodistribution were assessed using
autoradiography. Tadpoles retained Se throughout metamorphosis, and partitioned
the element predominantly within digestive and excretory tissues, including
livers > mesonephros > guts > gallbladder. Importantly, our results demonstrate
that Se biodistribution varies significantly throughout development. This is
indicative of tissue transference, and particularly in tissues developing de novo
after depuration. To the best of our knowledge, this is the first study
demonstrating Se transference during metamorphic tissue remodelling. Further
research is warranted to explore the fate and metabolism of Se (and other metal
and metalloids) during anuran development and the implications of transference
for influencing toxicity.
PMID- 28423271
TI - Vertically Aligned Graphene Sheets Membrane for Highly Efficient Solar Thermal
Generation of Clean Water.
AB - Efficient utilization of solar energy for clean water is an attractive,
renewable, and environment friendly way to solve the long-standing water crisis.
For this task, we prepared the long-range vertically aligned graphene sheets
membrane (VA-GSM) as the highly efficient solar thermal converter for generation
of clean water. The VA-GSM was prepared by the antifreeze-assisted freezing
technique we developed, which possessed the run-through channels facilitating the
water transport, high light absorption capacity for excellent photothermal
transduction, and the extraordinary stability in rigorous conditions. As a
result, VA-GSM has achieved average water evaporation rates of 1.62 and 6.25 kg m
2 h-1 under 1 and 4 sun illumination with a superb solar thermal conversion
efficiency of up to 86.5% and 94.2%, respectively, better than that of most
carbon materials reported previously, which can efficiently produce the clean
water from seawater, common wastewater, and even concentrated acid and/or alkali
solutions.
PMID- 28423272
TI - Distinguishing Lead and Molecule States in Graphene-Based Single-Electron
Transistors.
AB - Graphene provides a two-dimensional platform for contacting individual molecules,
which enables transport spectroscopy of molecular orbital, spin, and vibrational
states. Here we report single-electron tunneling through a molecule that has been
anchored to two graphene leads. Quantum interference within the graphene leads
gives rise to an energy-dependent transmission and fluctuations in the sequential
tunnel-rates. The lead states are electrostatically tuned by a global back-gate,
resulting in a distinct pattern of varying intensity in the measured conductance
maps. This pattern could potentially obscure transport features that are
intrinsic to the molecule under investigation. Using ensemble averaged magneto
conductance measurements, lead and molecule states are disentangled, enabling
spectroscopic investigation of the single molecule.
PMID- 28423273
TI - Conformational Dynamics of Mechanically Compliant DNA Nanostructures from Coarse
Grained Molecular Dynamics Simulations.
AB - Structural DNA nanotechnology, the assembly of rigid 3D structures of complex yet
precise geometries, has recently been used to design dynamic, mechanically
compliant nanostructures with tunable equilibrium conformations and
conformational distributions. Here we use coarse-grained molecular dynamics
simulations to provide insights into the conformational dynamics of a set of
mechanically compliant DNA nanostructures-DNA hinges that use single-stranded DNA
"springs" to tune the equilibrium conformation of a layered double-stranded DNA
"joint" connecting two stiff "arms" constructed from DNA helix bundles. The
simulations reproduce the experimentally measured equilibrium angles between
hinge arms for a range of hinge designs. The hinges are found to be structurally
stable, except for some fraying of the open ends of the DNA helices comprising
the hinge arms and some loss of base-pairing interactions in the joint regions
coinciding with the crossover junctions, especially in hinges designed to exhibit
a small bending angle that exhibit large local stresses resulting in strong kinks
in their joints. Principal component analysis reveals that while the hinge
dynamics are dominated by bending motion, some twisting and sliding of hinge arms
relative to each other also exists. Forced deformation of the hinges reveals
distinct bending mechanisms for hinges with short, inextensible springs versus
those with longer, more extensible springs. Lastly, we introduce an approach for
rapidly predicting equilibrium hinge angles from individual force-deformation
behaviors of its single- and double-stranded DNA components. Taken together,
these results demonstrate that coarse-grained modeling is a promising approach
for designing, predicting, and studying the dynamics of compliant DNA
nanostructures, where conformational fluctuations become important, multiple
deformation mechanisms exist, and continuum approaches may not yield accurate
properties.
PMID- 28423274
TI - Experimental Evidence of Long-Range Intramolecular Vibrational Energy
Redistribution through Eight Covalent Bonds: NIR Irradiation Induced
Conformational Transformation of E-Glutaconic Acid.
AB - Long-range intramolecular vibrational energy redistribution (IVR) driven
conformational changes were investigated in a matrix-isolated open-chain,
asymmetrical dicarboxylic acid, E-glutaconic acid. Although the analysis was
challenging due to the presence of multiple backbone conformers and short
lifetimes of the prepared higher energy cis conformers, it was shown that the
selective excitation of the O-H stretching overtone of one of the carboxylic
groups can induce the conformational change (trans to cis) of the other
carboxylic group, located at the other end of the E-glutaconic acid molecule.
This is a direct proof that the IVR process can act through eight covalent bonds
in a flexible molecule before the excess energy completely dissipates into the
matrix. The lifetime of the prepared higher energy conformers (averaged over the
different backbones) was measured to be 12 s.
PMID- 28423275
TI - Single or Multiple Access Channels to the CYP450s Active Site? An Answer from
Free Energy Simulations of the Human Aromatase Enzyme.
AB - Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical
targets of breast and prostate anticancer therapies, critical players in drug
metabolism, and their overexpression in tumors is associated with drug
resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in
deeply buried active sites accessible only via several grueling channels, whose
exact biological role remains unclear. Gaining direct insights on the mechanism
by which ligands travel in and out is becoming increasingly important given that
channels are involved in the modulation of binding/dissociation kinetics and the
specificity of ligands toward a CYP450. This has profound implications for
enzymatic efficiency and drug efficacy/toxicity. Here, by applying free energy
methods, for a cumulative simulation time of 20 MUs, we provide detailed
atomistic characterization and free energy profiles of the entry/exit routes
preferentially followed by a substrate (androstenedione) and a last-generation
inhibitor (letrozole) to/from the catalytic site of CYP19A1 (the human aromatase
(HA) enzyme), a key clinical target against breast cancer, studied here as
prototypical CYP450. Despite the remarkably different size/shape/hydrophobicity
of the ligands, two channels appear accessible to their entrance, while only one
exit route appears to be preferential. Our study shows that the preferential
paths may be conserved among different CYP450s. Moreover, our results highlight
that, at least in the case of HA, ligand channeling is associated with large
enzyme structural rearrangements. A wise choice of the computational method and
very long simulations are, thus, required to obtain fully converged quantitative
free energy profiles, which might be used to design novel biocatalysts or next
generation cytochrome inhibitors with an in silico tuned Km.
PMID- 28423276
TI - Supramolecular beta-Sheets Stabilized Protein Nanocarriers for Drug Delivery and
Gene Transfection.
AB - Suckerin proteins, recently discovered in the sucker ring teeth of squids,
represent a family of promising structural biomacromolecules that can form
supramolecular networks stabilized by nanoconfined beta-sheets. Exploiting this
feature as well as their specific amino acid composition, we demonstrate that
artificial suckerin-19 (S-19) can be engineered into nanocarriers for efficient
drug delivery and gene transfection in vitro and in vivo. First, we demonstrate
that S-19 self-assembles into beta-sheet stabilized nanoparticles with controlled
particle sizes of 100-200 nm that are able to encapsulate hydrophobic drugs for
pH-dependent release in vitro, and that can effectively inhibit tumor growth in
vivo. We also show that S-19 can complex and stabilize plasmid DNA, with the
complexes stabilized by hydrophobic interactions of the beta-sheet domains as
opposed to electrostatic interactions commonly achieved with cationic polymers,
thus lowering cytotoxicity. The elevated Histidine content of S-19 appears
critical to trigger endosomal escape by the proton sponge effect, thereby
ensuring efficient gene transfection both in vitro and in vivo. Our study
demonstrates that S-19 represents a promising functional protein nanocarrier that
could be used for various drug and gene delivery applications.
PMID- 28423277
TI - Controlling the Intermediate Structure of an Ionic Liquid for f-Block Element
Separations.
AB - Recent research has revealed molecular structure beyond the inner coordination
sphere is essential in defining the performance of separation processes;
nevertheless, such structure remains largely unexplored. Here we apply small
angle neutron scattering (SANS) and X-ray absorption fine structure (XAFS)
spectroscopy to investigate the structure of an ionic liquid system studied for f
block element separations. SANS data reveal dramatic changes in the ionic liquid
microstructure (~150 A) which we demonstrate can be controlled by judicious
selection of counterion. Mesoscale structural features (>500 A) are also observed
as a function of metal concentration. XAFS analysis supports formation of
extended aggregate structures, similar to those observed in traditional solvent
extraction processes, and suggests additional parallels may be drawn from further
study. Achieving precise tunability over the intermediate features is an
important development in controlling mesoscale structure and realizing advanced
new forms of soft matter.
PMID- 28423278
TI - Shapes of Splattered Drops.
AB - Drops that impact and stick to a surface (splattered drops) commonly show
noncircular triple lines. Physical or chemical defects on the surface are known
to pin the triple line in this static metastable state. We report an experimental
study to relate the defect distribution on a surface to the triple-line
microstructure of such drops. Triple lines of an ensemble of splattered drops
have been imaged on a range of surfaces varying in wetting properties. Local
contact angles have been calculated, and the microscale pinning force
distribution has been estimated. We propose a novel method of estimating defect
strength distribution from the pinning forces, using extreme value analysis. From
this analysis, we show that pinning force distributions have finite upper and
lower bounds. We show that most common surfaces show both hydrophobic and
hydrophilic defects, but their strength distributions are asymmetric in relation
to the surface's advancing and receding angles. In addition, we show that the
range of microscopic pinning forces varies linearly with macroscopic contact
angle hysteresis but, surprisingly, with a nonzero intercept. We explain the
intercept by drawing an analogy to static and dynamic friction.
PMID- 28423279
TI - NgMCp+: Noble Gas Bound Half-Sandwich Complexes (Ng = He-Rn, M = Be-Ba, and Cp =
eta5-C5H5).
AB - Structures, bonding, and stability of half-sandwich complexes with general
formula, NgMCp+ (Ng = He-Rn, M = Be-Ba, Cp = eta5-C5H5) are analyzed through ab
initio computation. MCp+ complexes possess remarkable Ng binding ability,
particularly for M = Be and Mg. While for Ar-Rn bound analogues the bond
dissociation energy in the former complex ranges within 17.5-28.0 kcal mol-1, it
becomes 10.4-18.7 kcal mol-1 in the latter complex. In fact, BeCp+ is able to
form a strong bond with the two most inert elements, He and Ne. Although the Ng
binding ability of MCp+ gradually diminishes in moving from Be to Ba, the
corresponding free energy change values show that Kr-Rn bound complexes involving
the heavier congeners of Mg would remain in the bound state avoiding dissociation
into Ng and MCp+. The nature of the Ng-M bond is characterized by natural bond
orbital, electron density and energy decomposition analyses in conjunction with
the natural orbital for chemical valence (EDA-NOCV) analysis. While the electron
density analysis reveals that Ng-Be (Ng = Kr, Xe, Rn) and Ng-Mg (Ng = Xe, Rn)
bonds are partly covalent in nature, the orbital interaction (DeltaEorb) is found
to be the most important term in the Ng-M attractive energy as revealed by the
EDA-NOCV. For all Ngs, the major contribution toward the DeltaEorb energy term
originates from Ng->MCp+ sigma-donation. Additionally, CpBeNgF (Ng = Xe, Rn) and
CpNgF (Ng = Kr-Rn) are found to be viable systems with kinetic protection for the
exergonic dissociation channels, CpBeNgF -> Ng + CpBeF and CpNgF -> Ng + CpF,
respectively, where the activation free energy barrier in the latter systems
(24.1-34.7 kcal mol-1) is significantly larger than that in the former ones (6.6
8.9 kcal mol-1). CpNgF (Ng = Kr-Rn) complexes are predicted to be stable even
above 300 K, whereas CpBeNgF (Ng = Xe, Rn) would be viable up to ~100 K. While
the F-Ng bonds are ionic in nature, the Ng-Be and Ng-C bonds in these complexes
have significant covalent character.
PMID- 28423280
TI - Does a Nitrogen Lone Pair Lead to Two Centered-Three Electron (2c-3e)
Interactions in Pyridyl Radical Isomers?
AB - Each of the three isomeric pyridyl radicals (2-, 3-, and 4-dehydropyridines)
contains a lone pair and an unpaired electron. As a result, a potential two
centered-three electron interaction between the radical electron and the lone
pair through-space (TS) and/or through-bond (TB) can exist that may influence the
stability of the radicals. Due to the change in geometrical positions relative to
each other, the strength of interaction can be varied. In this study, we
investigated the structural and stability aspects of pyridyl radical isomers with
a major emphasis on the interaction of a nitrogen lone pair with the radical
center. In order to obtain evidence for such interactions, protonated and N-oxide
analogues of the corresponding isomeric pyridyl radicals have been considered in
such a way to understand the consequences due to unavailability of the lone pair.
Similarly, electron attachment and detachment energies at the radical center
(vertical detachment energy, VDE, of corresponding anions and vertical ionization
energy, VIE, of radical isomers) have been calculated to find out the interaction
trend upon modification at the radical center. Different levels of theory
including (U)B3LYP/cc-pVTZ, (U)M06/cc-pVTZ, CBS-QB3, single-point energy
calculations at (U)CCSD(T)/cc-pVTZ, and multireference CASSCF/cc-pVTZ methods
have been employed in this regard. A closer inspection of geometries, relative
stability order, spin density, electrostatic potential, molecular orbitals, NBO
analysis, and vibrational analysis have showed a strong and stabilizing TS
interaction between the radical center and the lone pair in the case of the 2
pyridyl radical. On the other hand, the 4-pyridyl radical showed stabilizing
interactions only via TB coupling, whereas the TS interaction is nonexistent.
Despite the presence of both interactions in the case of the 3-pyridyl radical,
their overall influence is less effective toward stability.
PMID- 28423281
TI - An aqueous extract from Moringa oleifera leaves ameliorates hepatotoxicity in
alloxan-induced diabetic rats.
AB - This study was carried out to evaluate the possible mechanisms through which an
aqueous extract from MO leaves demonstrates hepatoprotective effects in alloxan
induced diabetic rats. Eighty albino rats were assigned to 4 groups. The control
group was orally administered sterile saline. The second group was injected with
alloxan (150 mg/kg body mass (b.m.)) by intraperitoneal injection (i.p.). The
third group was given MO (250 mg/kg b.m.) orally, daily. The fourth group was
injected with alloxan, as for the second group, and administrated an aqueous
extract of MO leaves, as for the third group. Alloxan induced degenerative
changes in hepatic and pancreatic tissues, increased hepatic lipid peroxidation,
and increased gene expression of PC and caspase 3. However, it decreased the
activities of hepatic SOD and CAT, and gene expression of GS. In contrast, the MO
extract prevented changes to the histoarchitecture of hepatic and pancreatic
tissues and normalized the reduced hepatic levels of glutathione, as well as the
activities of SOD and CAT, and the gene expression of GS, while reducing blood
glucose levels, hepatic lipid peroxidation, and the gene expression of PC and
caspase 3. This study indicated that an aqueous extract of MO leaves can be a
potent antioxidant and used as an hepatoprotective agent.
PMID- 28423282
TI - Good Riddance to Big Insurance Mergers.
PMID- 28423283
TI - Reply: Controlled Clinical Trials and Real-Life Experience with Pulmonary
Rehabilitation.
PMID- 28423284
TI - Controlled Clinical Trials and Real-Life Experience with Pulmonary
Rehabilitation.
PMID- 28423285
TI - The Epidemiology of High Ankle Sprains in National Collegiate Athletic
Association Sports.
AB - BACKGROUND: Ankle sprains are among the most common injuries experienced by
collegiate athletes. The type of ankle sprain is rarely differentiated in
epidemiological studies. This differentiation is necessary, as each ankle sprain
type has a unique injury mechanism and recovery period. High ankle sprains
commonly result in long recovery periods. Thus, a further examination of the
epidemiology of high ankle sprains is warranted. PURPOSE: To describe the
epidemiology of high ankle sprains in National Collegiate Athletic Association
(NCAA) sports during the 2009/2010-2014/2015 academic years. STUDY DESIGN:
Descriptive epidemiology study. METHODS: NCAA Injury Surveillance Program high
ankle sprain data and athlete-exposures (AEs) from 25 sports were evaluated.
Certified athletic trainers recorded sport-related injury, event, and AE data
during team-sanctioned events. High ankle sprain injury rates per 10,000 AEs were
calculated. Percentage distributions were calculated for the amount of time lost
from sport and percentage of recurrent injuries. Injury rate ratios (RRs) and 95%
CIs compared injury rates by event type, participation restriction time, and sex.
95% CIs not containing 1.00 were considered statistically significant. RESULTS:
The overall high ankle sprain injury rate was 1.00 per 10,000 AEs. Overall, 56.7%
of high ankle sprain injuries occurred during competitions, and 9.8% of high
ankle sprain injuries were recurrent. Men's football (2.42/10,000 AEs), wrestling
(2.11/10,000 AEs), and ice hockey (1.19/10,000 AEs) had the highest high ankle
sprain injury rates. In sex-comparable sports, men had higher injury rates (RR,
1.77; 95% CI, 1.28-2.44). Player contact was the most common injury mechanism
(60.4%), and 69.0% of injuries resulted in >=1 day of participation restriction,
with 47.1% resulting in >=7 days of participation restriction and 15.8% resulting
in >21 days of participation restriction. CONCLUSION: High ankle sprains resulted
in significant participation restriction time from sport participation. The
majority of high ankle sprain injuries resulted from player contact and were
observed in contact/collision sports. The large proportion of high ankle sprains
resulting from player contact, specifically in male contact sports, is worthy of
further investigation. CLINICAL RELEVANCE: The enhanced understanding of the
epidemiology of high ankle sprains provided in our study will aid clinicians in
developing targeted injury prevention strategies to mitigate the negative
consequences of these injuries.
PMID- 28423286
TI - Protective effects of tempol in an experimental ovarian ischemia-reperfusion
injury model in female Wistar albino rats.
AB - The aim of this study was to investigate the antioxidant effects of tempol on
ovarian ischemia-reperfusion (I/R) injury in rats. Forty female Wistar albino
rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I);
Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50
mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia
group and the I/R group than in the sham group. Catalase levels were
significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and
the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower
in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50
mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30
mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group.
The levels of the histopathological parameters were significantly decreased in
the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be
used for reducing ovarian I/R injury.
PMID- 28423287
TI - Microfracture Versus Autologous Chondrocyte Implantation for Articular Cartilage
Lesions in the Knee: A Systematic Review of 5-Year Outcomes.
AB - BACKGROUND: Microfracture (MFx) and autologous chondrocyte implantation (ACI) are
2 surgical treatment options used to treat articular cartilage injuries of the
knee joint. PURPOSE: To compare the midterm to long-term clinical outcomes of MFx
versus ACI for focal chondral defects of the knee. STUDY DESIGN: Systematic
review. METHODS: A systematic review was performed by searching PubMed, the
Cochrane Library, and Embase to locate studies (level of evidence I-III)
comparing the minimum average 5-year clinical outcomes of patients undergoing MFx
versus ACI. Search terms used were "knee," "microfracture," "autologous
chondrocyte implantation," and "autologous chondrocyte transplantation." Patients
were evaluated based on treatment failure rates, magnetic resonance imaging, and
patient-reported outcome scores (Lysholm, Knee Injury and Osteoarthritis Outcome
Score [KOOS], and Tegner scores). RESULTS: Five studies (3 level I evidence, 2
level II evidence) were identified that met the inclusion criteria, including a
total of 210 patients (211 lesions) undergoing MFx and 189 patients (189 lesions)
undergoing ACI. The average follow-up among all studies was 7.0 years. Four
studies utilized first-generation, periosteum-based ACI (P-ACI), and 1 study
utilized third-generation, matrix-associated ACI (M-ACI). Treatment failure
occurred in 18.5% of patients undergoing ACI and 17.1% of patients undergoing MFx
( P = .70). Lysholm and KOOS scores were found to improve for both groups across
studies, without a significant difference in improvement between the groups. The
only significant difference in patient-reported outcome scores was found in the 1
study using M-ACI in which Tegner scores improved to a significantly greater
extent in the ACI group compared with the MFx group ( P = .003). CONCLUSION:
Patients undergoing MFx or first/third-generation ACI for articular cartilage
lesions in the knee can be expected to experience improvement in clinical
outcomes at midterm to long-term follow-up without any significant difference
between the groups.
PMID- 28423288
TI - Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality
Therapy-The Yale Experience.
AB - In the article by Koletsky et al "Second Neoplasms in Patients With Hodgkin's
Disease Following Combined Modality Therapy-The Yale Experience" (Journal of
Clinical Oncology 4:311-317, 1986), an error was made in the footnote on page 311
which described the composition of MVVPP. The corrected footnote appears below.
*MVVPP = nitrogen mustard (0.4 mg/kg on day 1 of cycle); vinblastine (6 mg/m2 on
days 22, 29, and 36); vincristine (1.4 mg/m2, 2 mg maximum dose, on days 1, 8,
and 15); procarbazine (100 mg/d on days 22 through 42); prednisone (40 mg/m2 on
days 1 through 15 for cycles 1, 3, and 5 only).
PMID- 28423289
TI - Reevaluating Eligibility Criteria - Balancing Patient Protection and
Participation in Oncology Trials.
PMID- 28423290
TI - Sickle Cell Disease.
PMID- 28423291
TI - Addressing the Opioid Epidemic - Opportunities in the Postmarketing Setting.
PMID- 28423292
TI - Case 12-2017 - A 34-Year-Old Man with Nephropathy.
PMID- 28423293
TI - Screening for Diabetic Retinopathy.
PMID- 28423294
TI - Screening for Colorectal Neoplasia.
PMID- 28423295
TI - Screening for Colorectal Neoplasia.
PMID- 28423297
TI - Osteopetrosis.
PMID- 28423296
TI - Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia.
AB - BACKGROUND: Acquired aplastic anemia results from immune-mediated destruction of
bone marrow. Immunosuppressive therapies are effective, but reduced numbers of
residual stem cells may limit their efficacy. In patients with aplastic anemia
that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin
receptor agonist, led to clinically significant increases in blood counts in
almost half the patients. We combined standard immunosuppressive therapy with
eltrombopag in previously untreated patients with severe aplastic anemia.
METHODS: We enrolled 92 consecutive patients in a prospective phase 1-2 study of
immunosuppressive therapy plus eltrombopag. The three consecutively enrolled
cohorts differed with regard to the timing of initiation and the duration of the
eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months,
cohort 2 from day 14 to 3 months, and cohort 3 from day 1 to 6 months). The
cohorts were analyzed separately. The primary outcome was complete hematologic
response at 6 months. Secondary end points included overall response, survival,
relapse, and clonal evolution to myeloid cancer. RESULTS: The rate of complete
response at 6 months was 33% in cohort 1, 26% in cohort 2, and 58% in cohort 3.
The overall response rates at 6 months were 80%, 87%, and 94%, respectively. The
complete and overall response rates in the combined cohorts were higher than in
our historical cohort, in which the rate of complete response was 10% and the
overall response rate was 66%. At a median follow-up of 2 years, the survival
rate was 97%; one patient died during the study from a nonhematologic cause.
Marked increases in bone marrow cellularity, CD34+ cell number, and frequency of
early hematopoietic progenitors were noted. Rates of relapse and clonal evolution
were similar to our historical experience. Severe rashes occurred in two
patients, resulting in the early discontinuation of eltrombopag. CONCLUSIONS: The
addition of eltrombopag to immunosuppressive therapy was associated with markedly
higher rates of hematologic response among patients with severe aplastic anemia
than in a historical cohort. (Funded by the National Heart, Lung, and Blood
Institute; ClinicalTrials.gov number, NCT01623167 .).
PMID- 28423298
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28423299
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28423300
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28423301
TI - Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis.
AB - BACKGROUND: Interleukin-23 is thought to be critical to the pathogenesis of
psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal
antibody that inhibits interleukin-23 by specifically targeting the p19 subunit
and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12
and interleukin-23 inhibitor, in patients with moderate-to-severe plaque
psoriasis. METHODS: We randomly assigned a total of 166 patients to receive
subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg
or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to
body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater
reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at
week 12. RESULTS: At week 12, the percentage of patients with a 90% or greater
reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg
and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for
ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the
PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as
compared with 18% in the ustekinumab group. Efficacy was generally maintained up
to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg
and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6
patients (15%), and 3 patients (8%), respectively, had serious adverse events,
including two basal-cell carcinomas and one major cardiovascular adverse event;
there were no serious adverse events in the 180-mg risankizumab group.
CONCLUSIONS: In this phase 2 trial, selective blockade of interleukin-23 with
risankizumab was associated with clinical responses superior to those associated
with ustekinumab. This trial was not large enough or of long enough duration to
draw conclusions about safety. (Funded by Boehringer Ingelheim;
ClinicalTrials.gov number, NCT02054481 ).
PMID- 28423302
TI - "Zombie" Outbreak Caused by Synthetic Cannabinoid.
PMID- 28423303
TI - "Zombie" Outbreak Caused by Synthetic Cannabinoid.
PMID- 28423304
TI - Candida Esophagitis.
PMID- 28423306
TI - Disclosure of newly diagnosed HIV infection and condom use at first sex after
diagnosis: a study of young Black men who have sex with men.
AB - : Background The first purpose of the present study was to determine whether
young Black men who have sex with men (YBMSM) disclose their newly diagnosed HIV
infection to a male or female partner, and to determine whether this disclosure
is related to condom use; the second was to identify correlates of disclosing
newly diagnosed HIV infection to male sex partners, including a measure of
partner-related barriers to condom use. METHODS: A sample of 125 HIV-infected
YBMSM (age 15-29 years) provided cross-sectional data used for both study
purposes. Recruitment occurred in a mid-size city in the southern US experiencing
inordinately high prevalence and incidence rates of HIV among YBMSM. Significance
was defined by an alpha level of <0.05. RESULTS: Eighty-eight YBMSM (70.4%)
indicated disclosing their newly diagnosed HIV status to the first male partner
they had sex with after being diagnosed. Of these, nine (9.1%) reported that
condoms were not used during ensuing sex with that partner. However, of the men
not disclosing, 27.0% reported not using condoms for ensuing sex (P=0.009).
Similar findings were observed relative to sex with females (P=0.057). Regarding
the second study purpose, in addition to a protective effect of advancing age,
men scoring at or above the median on a measure of partner-related barriers to
condom use were 2.4-fold more likely to not disclose compared with men scoring
below the median (P=0.04). CONCLUSION: For YBMSM, a beneficial counselling
objective relative to disclosing newly diagnosed HIV may be to help men resolve
perceptions of partner-related barriers to condom use.
PMID- 28423307
TI - Aspects of phosphorus physiology associated with phosphate-induced polar lipid
remodelling in marine microalgae.
AB - Marine microalgae exhibit a diversified phosphorus physiology and have also been
recently found to show high inter-taxa variability in their phosphate induced
polar lipids' remodelling. Identification of phosphorus physiology aspects that
are more related to lipid remodelling can contribute to better understanding of
such intricate phytoplankton lipid metabolism. Therefore, some aspects of
phosphorus physiology related to its uptake, storage and use were evaluated in a
taxonomically diversified group of nine marine microalgae that was arranged into
three subgroups, each of them including species showing similar polar lipid
responses to phosphate. Luxury phosphate uptake (PU) was the physiological aspect
best associated to microalgal polar lipid metabolism as it was maximal in species
(Picochlorum atomus, Tetraselmis suecica and Nannochloropsis gaditana) that were
able to counterbalance between phospholipids (PL) and betaine lipids (BL).
Cryptophytes (Rhodomonas baltica, Chroomonas placoidea), characterized by their
constitutive BL and flexible PL contents in response to phosphate, had almost no
luxury PU and showed higher phosphorus cell quota (QP) under phosphate
deprivation. Haptophyes (Isochrysis galbana, Diacronema vlkianum), with
constitutive BL contents and permanently minimal PL contents, showed the lowest
QP when deprived of phosphate while their luxury PU was below that for green
microalgae. Induction of alkaline phosphatase activity following phosphate
depletion was maximal in diatoms (Phaeodactylum tricornutum, Chaetoceros
gracilis) and I. galbana but it was unrelated to lipid remodelling. Despite
strong influence of taxonomy, polar lipid remodelling accounted for 38.8% of
total variation when microalgae were ordinated using their physiological
responses to phosphorus as descriptive variables.
PMID- 28423308
TI - How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life
Decrepitude.
AB - The goal of aging research is to extend healthy, active life. For decades, C.
elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutants have
served as a model for extended lifespan and youthfulness. However, a recent
report suggested that their longevity is associated with an undesirable
phenotype: a disproportionately long period of decrepitude at the end of life. In
the human population, such an outcome would be a burden to society, bringing into
question the relevance of daf-2 mutants as a model for life extension. However,
here we report that, following an extended period of movement, daf-2 mutants
survive longer in a decrepit state because of a beneficial trait: they are
resistant to colonization of the digestive tract by dietary bacteria, a condition
that leads to premature death in the wild-type and prevents their manifestation
of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead
both chronologically and proportionately healthier lives relative to the wild
type.
PMID- 28423309
TI - The Natural Product Cavinafungin Selectively Interferes with Zika and Dengue
Virus Replication by Inhibition of the Host Signal Peptidase.
AB - Flavivirus infections by Zika and dengue virus impose a significant global
healthcare threat with no US Food and Drug Administration (FDA)-approved
vaccination or specific antiviral treatment available. Here, we present the
discovery of an anti-flaviviral natural product named cavinafungin. Cavinafungin
is a potent and selectively active compound against Zika and all four dengue
virus serotypes. Unbiased, genome-wide genomic profiling in human cells using a
novel CRISPR/Cas9 protocol identified the endoplasmic-reticulum-localized signal
peptidase as the efficacy target of cavinafungin. Orthogonal profiling in S.
cerevisiae followed by the selection of resistant mutants pinpointed the
catalytic subunit of the signal peptidase SEC11 as the evolutionary conserved
target. Biochemical analysis confirmed a rapid block of signal sequence cleavage
of both host and viral proteins by cavinafungin. This study provides an effective
compound against the eukaryotic signal peptidase and independent confirmation of
the recently identified critical role of the signal peptidase in the replicative
cycle of flaviviruses.
PMID- 28423310
TI - c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to
Coordinate Antibody Responses.
AB - Humoral immune responses are tailored to the invading pathogen through regulation
of key transcription factors and their networks. This is critical to establishing
effective antibody-mediated responses, yet it is unknown how B cells integrate
pathogen-induced signals to drive or suppress transcriptional programs
specialized for each class of pathogen. Here, we detail the key role of the
transcription factor c-Myb in regulating the T-bet-mediated anti-viral program.
Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3
expression by upregulating T-bet, normally suppressed during Th2-cell-mediated
responses. Enhanced expression of T-bet resulted in aberrant plasma cell
differentiation within the germinal center, mediated by CXCR3 expression. These
findings identify a dual role for c-Myb in limiting inappropriate effector
responses while coordinating plasma cell differentiation with germinal center
egress. Identifying such intrinsic regulators of specialized antibody responses
can assist in vaccine design and therapeutic intervention in B-cell-mediated
immune disorders.
PMID- 28423311
TI - Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult
Mammalian Carotid Body.
AB - Adult stem cell plasticity, or the ability of somatic stem cells to cross
boundaries and differentiate into unrelated cell types, has been a matter of
debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a
remarkable plasticity during development. Whether adult populations of NCSCs
retain this plasticity is largely unknown. Herein, we describe that neural-crest
derived adult carotid body stem cells (CBSCs) are able to undergo endothelial
differentiation in addition to their reported role in neurogenesis, contributing
to both neurogenic and angiogenic processes taking place in the organ during
acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is
hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released
vascular cytokines such as erythropoietin. Our data highlight a remarkable
physiological plasticity in an adult population of tissue-specific stem cells and
could have impact on the use of these cells for cell therapy.
PMID- 28423312
TI - HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem
Cells into GAlert.
AB - The activation of quiescent stem cells into the cell cycle is a key step in
initiating the process of tissue repair. We recently reported that quiescent stem
cells can transition into GAlert, a cellular state in which they have an
increased functional ability to activate and participate in tissue repair.
However, the precise molecular signals that induce GAlert in stem cells have
remained elusive. Here, we show that the injury-induced regulation of hepatocyte
growth factor (HGF) proteolytic processing via the systemic protease, hepatocyte
growth factor activator (HGFA), stimulates GAlert in skeletal muscle stem cells
(MuSCs) and fibro-adipogenic progenitors (FAPs). We demonstrate that
administering active HGFA to animals is sufficient to induce GAlert in stem cells
throughout the body and to significantly accelerate the processes of stem cell
activation and tissue repair. Our data suggest that factors that induce GAlert
will have broad therapeutic applications for regenerative medicine and wound
healing.
PMID- 28423314
TI - Cyanobacteria Maintain Constant Protein Concentration despite Genome Copy-Number
Variation.
AB - The cyanobacterium Synechococcus elongatus PCC 7942 has multiple copies of its
single chromosome, and the copy number varies in individual cells, providing an
ideal system to study the effect of genome copy-number variation on cell size and
gene expression. Using single-cell fluorescence imaging, we found that protein
concentration remained constant across individual cells regardless of genome copy
number. Cell volume and the total protein amount from a single gene were both
positively, linearly correlated with genome copy number, suggesting that changes
in cell volume play an important role in buffering genome copy-number variance.
This study provides a quantitative examination of gene expression regulation in
cells with variable genome copies and sheds light on the compensation mechanisms
for variance in genome copy number.
PMID- 28423305
TI - Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes.
AB - BACKGROUND: In patients who have had type 1 diabetes for 5 years, current
recommendations regarding screening for diabetic retinopathy include annual
dilated retinal examinations to detect proliferative retinopathy or clinically
significant macular edema, both of which require timely intervention to preserve
vision. During 30 years of the Diabetes Control and Complications Trial (DCCT)
and its longitudinal follow-up Epidemiology of Diabetes Interventions and
Complications (EDIC) study, retinal photography was performed at intervals of 6
months to 4 years. METHODS: We used retinal photographs from the DCCT/EDIC study
to develop a rational screening frequency for retinopathy. Markov modeling was
used to determine the likelihood of progression to proliferative diabetic
retinopathy or clinically significant macular edema in patients with various
initial retinopathy levels (no retinopathy or mild, moderate, or severe
nonproliferative diabetic retinopathy). The models included recognized risk
factors for progression of retinopathy. RESULTS: Overall, the probability of
progression to proliferative diabetic retinopathy or clinically significant
macular edema was limited to approximately 5% between retinal screening
examinations at 4 years among patients who had no retinopathy, 3 years among
those with mild retinopathy, 6 months among those with moderate retinopathy, and
3 months among those with severe nonproliferative diabetic retinopathy. The risk
of progression was also closely related to mean glycated hemoglobin levels. The
risk of progression from no retinopathy to proliferative diabetic retinopathy or
clinically significant macular edema was 1.0% over 5 years among patients with a
glycated hemoglobin level of 6%, as compared with 4.3% over 3 years among
patients with a glycated hemoglobin level of 10%. Over a 20-year period, the
frequency of eye examinations was 58% lower with our practical, evidence-based
schedule than with routine annual examinations, which resulted in substantial
cost savings. CONCLUSIONS: Our model for establishing an individualized schedule
for retinopathy screening on the basis of the patient's current state of
retinopathy and glycated hemoglobin level reduced the frequency of eye
examinations without delaying the diagnosis of clinically significant disease.
(Funded by the National Institute of Diabetes and Digestive and Kidney Diseases
and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360893 and NCT00360815 .).
PMID- 28423313
TI - Power Grid Protection of the Muscle Mitochondrial Reticulum.
AB - Mitochondrial network connectivity enables rapid communication and distribution
of potential energy throughout the cell. However, this connectivity puts the
energy conversion system at risk, because damaged elements could jeopardize the
entire network. Here, we demonstrate the mechanisms for mitochondrial network
protection in heart and skeletal muscle (SKM). We find that the cardiac
mitochondrial reticulum is segmented into subnetworks comprising many
mitochondria linked through abundant contact sites at highly specific
intermitochondrial junctions (IMJs). In both cardiac and SKM subnetworks, a rapid
electrical and physical separation of malfunctioning mitochondria occurs,
consistent with detachment of IMJs and retraction of elongated mitochondria into
condensed structures. Regional mitochondrial subnetworks limit the cellular
impact of local dysfunction while the dynamic disconnection of damaged
mitochondria allows the remaining mitochondria to resume normal function within
seconds. Thus, mitochondrial network security is comprised of both proactive and
reactive mechanisms in striated muscle cells.
PMID- 28423315
TI - miR-132/212 Modulates Seasonal Adaptation and Dendritic Morphology of the Central
Circadian Clock.
AB - The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day
length information by mechanisms that are not well understood. Here, we report
that genetic ablation of miR-132/212 alters entrainment to different day lengths
and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2
expression in the SCN. SCN neurons from miR-132/212-deficient mice have
significantly reduced dendritic spine density, along with altered methyl CpG
binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day
length regulates spine density on SCN neurons in a melatonin-independent manner,
as well as expression of miR-132, miR-212, and their direct target, MeCP2.
Genetic disruption of Mecp2 fully restores the level of dendritic spines of miR
132/212-deficient SCN neurons. Our results reveal that, by regulating the
dendritic structure of SCN neurons through a MeCP2-dependent mechanism, miR
132/212 affects the capacity of the SCN to encode seasonal time.
PMID- 28423316
TI - Diversity in Excitation-Inhibition Mismatch Underlies Local Functional
Heterogeneity in the Rat Auditory Cortex.
AB - Cortical neurons are heterogeneous in their functional properties. This
heterogeneity is fundamental for the processing of different features of sensory
information. However, functional diversity within a local group of neurons is
poorly understood. Here, we demonstrate that neighboring cortical neurons in
layer 5 but not those of layer 4 of the rat anterior auditory field (AAF)
exhibited a surprisingly high level of diversity in tonal receptive fields. In
vivo whole-cell voltage-clamp recordings revealed that the diversity of frequency
representation was due to a spectral mismatch between synaptic excitation and
inhibition to varying degrees. The spectral distribution of excitation was skewed
at different levels, whereas inhibition was homogeneous and non-skewed, similar
to the summed spiking activity of local neuronal ensembles, which further
enhanced diversity. Our results indicate that AAF in the auditory cortex is
involved in processing auditory information in a highly refined manner that is
important for complex pattern recognition.
PMID- 28423317
TI - Loss of Navbeta4-Mediated Regulation of Sodium Currents in Adult Purkinje Neurons
Disrupts Firing and Impairs Motor Coordination and Balance.
AB - The resurgent component of voltage-gated Na+ (Nav) currents, INaR, has been
suggested to provide the depolarizing drive for high-frequency firing and to be
generated by voltage-dependent Nav channel block (at depolarized potentials) and
unblock (at hyperpolarized potentials) by the accessory Navbeta4 subunit. To test
these hypotheses, we examined the effects of the targeted deletion of Scn4b
(Navbeta4) on INaR and on repetitive firing in cerebellar Purkinje neurons. We
show here that Scn4b-/- animals have deficits in motor coordination and balance
and that firing rates in Scn4b-/- Purkinje neurons are markedly attenuated.
Acute, in vivo short hairpin RNA (shRNA)-mediated "knockdown" of Navbeta4 in
adult Purkinje neurons also reduced spontaneous and evoked firing rates. Dynamic
clamp-mediated addition of INaR partially rescued firing in Scn4b-/- Purkinje
neurons. Voltage-clamp experiments revealed that INaR was reduced (by ~50%), but
not eliminated, in Scn4b-/- Purkinje neurons, revealing that additional
mechanisms contribute to generation of INaR.
PMID- 28423318
TI - Oligodendrocyte Nf1 Controls Aberrant Notch Activation and Regulates Myelin
Structure and Behavior.
AB - The RASopathy neurofibromatosis type 1 (NF1) is one of the most common autosomal
dominant genetic disorders. In NF1 patients, neurological issues may result from
damaged myelin, and mice with a neurofibromin gene (Nf1) mutation show white
matter (WM) defects including myelin decompaction. Using mouse genetics, we find
that altered Nf1 gene-dose in mature oligodendrocytes results in progressive
myelin defects and behavioral abnormalities mediated by aberrant Notch
activation. Blocking Notch, upstream mitogen-activated protein kinase (MAPK), or
nitric oxide signaling rescues myelin defects in hemizygous Nf1 mutants, and
pharmacological gamma secretase inhibition rescues aberrant behavior with no
effects in wild-type (WT) mice. Concomitant pathway inhibition rescues myelin
abnormalities in homozygous mutants. Notch activation is also observed in Nf1+/-
mouse brains, and cells containing active Notch are increased in NF1 patient WM.
We thus identify Notch as an Nf1 effector regulating myelin structure and
behavior in a RASopathy and suggest that inhibition of Notch signaling may be a
therapeutic strategy for NF1.
PMID- 28423319
TI - TAM Receptors Are Not Required for Zika Virus Infection in Mice.
AB - Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection
with the Zika virus (ZIKV), an emerging flavivirus of global public health
concern. To investigate the requirement of TAM receptors for ZIKV infection, we
used several routes of viral inoculation and compared viral replication in wild
type versus Axl-/-, Mertk-/-, Axl-/-Mertk-/-, and Axl-/-Tyro3-/- mice in various
organs. Pregnant and non-pregnant mice treated with interferon-alpha-receptor
(IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed
no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody,
adult female mice challenged intravaginally with ZIKV showed no difference in
mucosal viral titers. Similarly, in young mice that were infected with ZIKV
intracranially or intraperitoneally, ZIKV replication occurred in the absence of
TAM receptors, and no differences in cell tropism were observed. These findings
indicate that, in mice, TAM receptors are not required for ZIKV entry and
infection.
PMID- 28423320
TI - Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+
TCR Repertoires to Immunodominant Viral Antigens.
AB - A diverse T cell receptor (TCR) repertoire is essential for controlling viral
infections. However, information about TCR repertoires to defined viral antigens
is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two
dominant viral epitopes: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL)
of influenza A virus. The highly individualized repertoires (87-5,533 alpha or
beta clonotypes per subject) comprised thousands of unique TCRalpha and TCRbeta
sequences and dozens of distinct complementary determining region (CDR)3alpha and
CDR3beta motifs. However, diversity is effectively restricted by preferential V-J
combinations, CDR3 lengths, and CDR3alpha/CDR3beta pairings. Structures of two
GIL-specific TCRs bound to GIL-HLA-A2 provided a potential explanation for the
lower diversity of GIL-specific versus NLV-specific repertoires. These anti-viral
TCRs occupied up to 3.4% of the CD8+ TCRbeta repertoire, ensuring broad T cell
responses to single epitopes. Our portrait of two anti-viral TCR repertoires may
inform the development of predictors of immune protection.
PMID- 28423321
TI - Hepatocellular Carcinomas Originate Predominantly from Hepatocytes and Benign
Lesions from Hepatic Progenitor Cells.
AB - Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer. However,
its origin remains a debated question. Using human data and various
hepatocarcinogenesis mouse models, we show that, in early stages, transformed
hepatocytes, independent of their proliferation status, activate hepatic
progenitor cell (HPC) expansion. Genetic lineage tracing of HPCs and hepatocytes
reveals that, in all models, HCC originates from hepatocytes. However, whereas in
various models tumors do not emanate from HPCs, tracking of progenitors in a
model mimicking human hepatocarcinogenesis indicates that HPCs can generate
benign lesions (regenerative nodules and adenomas) and aggressive HCCs.
Mechanistically, galectin-3 and alpha-ketoglutarate paracrine signals emanating
from oncogene-expressing hepatocytes instruct HPCs toward HCCs. alpha
Ketoglutarate preserves an HPC undifferentiated state, and galectin-3 maintains
HPC stemness, expansion, and aggressiveness. Pharmacological or genetic blockage
of galectin-3 reduces HCC, and its expression in human HCC correlates with poor
survival. Our findings may have clinical implications for liver regeneration and
HCC therapy.
PMID- 28423322
TI - Intratumoral Cancer Cell Intravasation Can Occur Independent of Invasion into the
Adjacent Stroma.
AB - Intravasation, active entry of cancer cells into the circulation, is often
considered to be a relatively late event in tumor development occurring after
stromal invasion. Here, we provide evidence that intravasation can be initiated
early during tumor development and proceed in parallel to or independent of tumor
invasion into surrounding stroma. By applying direct and unbiased intravasation
scoring methods to two histologically distinct human cancer types in live-animal
models, we demonstrate that intravasation takes place almost exclusively within
the tumor core, involves intratumoral vasculature, and does not involve
vasculotropic cancer cells invading tumor-adjacent stroma and migrating along
tumor-converging blood vessels. Highlighting an additional role for EGFR in
cancer, we find that EGFR is required for the development of an intravasation
sustaining intratumoral vasculature. Intratumoral localization of intravasation
supports the notion that overt metastases in cancer patients could be initiated
much earlier during cancer progression than appreciated within conventional
clinical tumor staging systems.
PMID- 28423323
TI - Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation
to Preferentially Phosphorylate Membrane Substrates.
AB - Protein kinase A (PKA) has diverse functions in neurons. At rest, the subcellular
localization of PKA is controlled by A-kinase anchoring proteins (AKAPs).
However, the dynamics of PKA upon activation remain poorly understood. Here, we
report that elevation of cyclic AMP (cAMP) in neuronal dendrites causes a
significant percentage of the PKA catalytic subunit (PKA-C) molecules to be
released from the regulatory subunit (PKA-R). Liberated PKA-C becomes associated
with the membrane via N-terminal myristoylation. This membrane association does
not require the interaction between PKA-R and AKAPs. It slows the mobility of PKA
C and enriches kinase activity on the membrane. Membrane-residing PKA substrates
are preferentially phosphorylated compared to cytosolic substrates. Finally, the
myristoylation of PKA-C is critical for normal synaptic function and plasticity.
We propose that activation-dependent association of PKA-C renders the membrane a
unique PKA-signaling compartment. Constrained mobility of PKA-C may synergize
with AKAP anchoring to determine specific PKA function in neurons.
PMID- 28423325
TI - Rapid Genome-wide Recruitment of RNA Polymerase II Drives Transcription,
Splicing, and Translation Events during T Cell Responses.
AB - Activation of immune cells results in rapid functional changes, but how such fast
changes are accomplished remains enigmatic. By combining time courses of 4sU-seq,
RNA-seq, ribosome profiling (RP), and RNA polymerase II (RNA Pol II) ChIP-seq
during T cell activation, we illustrate genome-wide temporal dynamics for ~10,000
genes. This approach reveals not only immediate-early and posttranscriptionally
regulated genes but also coupled changes in transcription and translation for
>90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily
mediates transcriptional changes. This coincides with a genome-wide temporary
slowdown in cotranscriptional splicing, even for polyadenylated mRNAs that are
localized at the chromatin. Subsequent splicing optimization correlates with
increasing Ser-2 phosphorylation of the RNA Pol II carboxy-terminal domain (CTD)
and activation of the positive transcription elongation factor (pTEFb). Thus,
rapid de novo recruitment of RNA Pol II dictates the course of events during T
cell activation, particularly transcription, splicing, and consequently
translation.
PMID- 28423324
TI - Resolving Subcellular miRNA Trafficking and Turnover at Single-Molecule
Resolution.
AB - Regulation of microRNA (miRNA) localization and stability is critical for their
extensive cytoplasmic RNA silencing activity and emerging nuclear functions.
Here, we have developed single-molecule fluorescence-based tools to assess the
subcellular trafficking, integrity, and activity of miRNAs. We find that seed
matched RNA targets protect miRNAs against degradation and enhance their nuclear
retention. While target-stabilized, functional, cytoplasmic miRNAs reside in high
molecular-weight complexes, nuclear miRNAs, as well as cytoplasmic miRNAs
targeted by complementary anti-miRNAs, are sequestered stably within
significantly lower-molecular-weight complexes and rendered repression
incompetent. miRNA stability and activity depend on Argonaute protein abundance,
whereas miRNA strand selection, unwinding, and nuclear retention depend on
Argonaute identity. Taken together, our results show that miRNA degradation
competes with Argonaute loading and target binding to control subcellular miRNA
abundance for gene silencing surveillance. Probing single cells for miRNA
activity, trafficking, and metabolism promises to facilitate screening for
effective miRNA mimics and anti-miRNA drugs.
PMID- 28423327
TI - Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression
Level.
PMID- 28423326
TI - Rapid Molecular Profiling of Defined Cell Types Using Viral TRAP.
AB - Translational profiling methodologies enable the systematic characterization of
cell types in complex tissues, such as the mammalian brain, where neuronal
isolation is exceptionally difficult. Here, we report a versatile strategy for
profiling CNS cell types in a spatiotemporally restricted fashion by engineering
a Cre-dependent adeno-associated virus expressing an EGFP-tagged ribosomal
protein (AAV-FLEX-EGFPL10a) to access translating mRNAs by translating ribosome
affinity purification (TRAP). We demonstrate the utility of this AAV to target a
variety of genetically and anatomically defined neural populations expressing Cre
recombinase and illustrate the ability of this viral TRAP (vTRAP) approach to
recapitulate the molecular profiles obtained by bacTRAP in corticothalamic
neurons across multiple serotypes. Furthermore, spatially restricting adeno
associated virus (AAV) injections enabled the elucidation of regional differences
in gene expression within this cell type. Altogether, these results establish the
broad applicability of the vTRAP strategy for the molecular dissection of any CNS
or peripheral cell type that can be engineered to express Cre.
PMID- 28423329
TI - The Dynamic Cytokine Niche.
AB - Immune cells communicate using cytokine signals, but the quantitative rules of
this communication aren't clear. In this issue of Immunity, Oyler-Yaniv et al.
(2017) suggest that the distribution of a cytokine within a lymphatic organ is
primarily governed by the local density of cells consuming it.
PMID- 28423328
TI - Treating Flu with Skin of Frog.
AB - Glands in frog skin secrete substances that possess broad antimicrobial function.
Holthausen et al. mined this soup of natural products and discovered a peptide
that destroys diverse human influenza strains (Holthausen et al., 2017). This
study points the way to the discovery of novel anti-influenza molecules targeting
conserved elements on influenza surface proteins.
PMID- 28423330
TI - The Birds, the Bees, and Innate Immunity.
AB - The cytoplasm is usually a DNA-free zone, but during fertilization, sperm DNA
enters oocyte cytoplasm and could potentially trigger a response. Abe et al.
(2017) identify NLRP14 as a germ-cell-specific negative regulator of DNA sensing
that may be of particular importance during fertilization.
PMID- 28423331
TI - Cell-Intrinsic Defense at the Epithelial Border Wall: Salmonella Pays the Price.
AB - Within the gut, Salmonella-infected enterocytes are expelled into the lumen,
limiting pathogen replication. In this issue of Immunity, Rauch et al. (2017)
expand our understanding of this cell-intrinsic response by characterizing the
genetic determinants that control the expulsion and death of epithelial cells.
PMID- 28423332
TI - Caught in the cROSsfire: GSH Controls T Cell Metabolic Reprogramming.
AB - T cell activation and proliferation critical for protective immunity depend on
appropriate rewiring of cellular metabolism. In this issue of Immunity, Mak et
al. (2017) show that the antioxidant gluthathione (GSH) controls reactive oxygen
species (ROS)-dependent engagement of metabolic signaling pathways that lead to
protective T cell responses.
PMID- 28423333
TI - Hunting Down the HIV-1 Reservoir: A Starring Role for Antibodies?
AB - The persistence of viruses "hidden" in a reservoir of latently infected CD4+ T
cells under antiretroviral therapy is the major obstacle to an HIV-1 cure.
Recently published in Nature, two seminal studies from Descours et al. (2017) and
Nishimura et al. (2017) bring hope for tracking and possibly eradicating the HIV
1 reservoir.
PMID- 28423334
TI - Two Strings in One Bow: PD-1 Negatively Regulates via Co-receptor CD28 on T
Cells.
AB - The identity of PD-1 dependency on other receptors and signaling has been
unclear. In a recent issue of Science, Hui et al. (2017) and Kamphorst et al.
(2017) now show that CD28 expression is a target of PD-1-associated phosphatases
and is needed for T cell expansion in anti-PD-1 immunotherapy.
PMID- 28423335
TI - Regionalized Development and Maintenance of the Intestinal Adaptive Immune
Landscape.
AB - The intestinal immune system has the daunting task of protecting us from
pathogenic insults while limiting inflammatory responses against the resident
commensal microbiota and providing tolerance to food antigens. This role is
particularly impressive when one considers the vast mucosal surface and changing
landscape that the intestinal immune system must monitor. In this review, we
highlight regional differences in the development and composition of the adaptive
immune landscape of the intestine and the impact of local intrinsic and
environmental factors that shape this process. To conclude, we review the
evidence for a critical window of opportunity for early-life exposures that
affect immune development and alter disease susceptibility later in life.
PMID- 28423336
TI - Lung Homeostasis: Influence of Age, Microbes, and the Immune System.
AB - Pulmonary immune homeostasis is maintained by a network of tissue-resident cells
that continually monitor the external environment, and in health, instruct
tolerance to innocuous inhaled particles while ensuring that efficient and rapid
immune responses can be mounted against invading pathogens. Here we review the
multiple pathways that underlie effective lung immunity in health, and discuss
how these may be affected by external environmental factors and contribute to
chronic inflammation during disease. In this context, we examine the current
understanding of the impact of the microbiota in immune development and function
and in the setting of the threshold for immune responses that maintains the
balance between tolerance and chronic inflammation in the lung. We propose that
host interactions with microbes are critical for establishing the immune
landscape of the lungs.
PMID- 28423338
TI - An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing
Influenza Viruses.
AB - Although vaccines confer protection against influenza A viruses, antiviral
treatment becomes the first line of defense during pandemics because there is
insufficient time to produce vaccines. Current antiviral drugs are susceptible to
drug resistance, and developing new antivirals is essential. We studied host
defense peptides from the skin of the South Indian frog and demonstrated that one
of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing
human influenza A viruses. This peptide specifically targeted the conserved stalk
region of H1 hemagglutinin and was effective against drug-resistant H1 influenza
viruses. Using electron microscopy, we showed that this peptide physically
destroyed influenza virions. It also protected naive mice from lethal influenza
infection. Urumin represents a unique class of anti-influenza virucide that
specifically targets the hemagglutinin stalk region, similar to targeting of
antibodies induced by universal influenza vaccines. Urumin therefore has the
potential to contribute to first-line anti-viral treatments during influenza
outbreaks.
PMID- 28423337
TI - Homeostatic Immunity and the Microbiota.
AB - The microbiota plays a fundamental role in the induction, education, and function
of the host immune system. In return, the host immune system has evolved multiple
means by which to maintain its symbiotic relationship with the microbiota. The
maintenance of this dialogue allows the induction of protective responses to
pathogens and the utilization of regulatory pathways involved in the sustained
tolerance to innocuous antigens. The ability of microbes to set the immunological
tone of tissues, both locally and systemically, requires tonic sensing of
microbes and complex feedback loops between innate and adaptive components of the
immune system. Here we review the dominant cellular mediators of these
interactions and discuss emerging themes associated with our current
understanding of the homeostatic immunological dialogue between the host and its
microbiota.
PMID- 28423339
TI - Germ-Cell-Specific Inflammasome Component NLRP14 Negatively Regulates Cytosolic
Nucleic Acid Sensing to Promote Fertilization.
AB - Cytosolic sensing of nucleic acids initiates tightly regulated programs to limit
infection. Oocyte fertilization represents a scenario wherein inappropriate
responses to exogenous yet non-pathogen-derived nucleic acids would have negative
consequences. We hypothesized that germ cells express negative regulators of
nucleic acid sensing (NAS) in steady state and applied an integrated data-mining
and functional genomics approach to identify a rheostat of DNA and RNA sensing
the inflammasome component NLRP14. We demonstrated that NLRP14 interacted
physically with the nucleic acid sensing pathway and targeted TBK1 (TANK binding
kinase 1) for ubiquitination and degradation. We further mapped domains in NLRP14
and TBK1 that mediated the inhibitory function. Finally, we identified a human
nonsense germline variant associated with male sterility that results in loss of
NLRP14 function and hyper-responsiveness to nucleic acids. The discovery points
to a mechanism of nucleic acid sensing regulation that may be of particular
importance in fertilization.
PMID- 28423340
TI - Transforming Growth Factor-beta Signaling in Regulatory T Cells Controls T Helper
17 Cells and Tissue-Specific Immune Responses.
AB - Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue
environments and against many inflammatory insults, yet the tissue-enriched
factor(s) that influence Treg cell phenotype and function remain largely unknown.
We have shown a vital role for transforming growth factor-beta (TGF-beta) signals
in safe-guarding specific Treg cell functions. TGF-beta signals were dispensable
for steady-state Treg cell homeostasis and for Treg cell suppression of T cell
proliferation and T helper-1 (Th1) cell differentiation. However, Treg cells
require TGF-beta signals to appropriately dampen Th17 cells and regulate
responses in the gastrointestinal tract. TGF-beta signaling maintains CD103
expression, promotes expression of the colon-specific trafficking molecule GPR15,
and inhibits expression of GPR174, a receptor for lysophosphatidylserine, on Treg
cells, collectively supporting the accumulation and retention of Treg cells in
the colon and control of colitogenic responses. Thus, we reveal an unrecognized
function for TGF-beta signaling as an upstream factor controlling Treg cell
activity in specific tissue environments.
PMID- 28423341
TI - Glutathione Primes T Cell Metabolism for Inflammation.
AB - Activated T cells produce reactive oxygen species (ROS), which trigger the
antioxidative glutathione (GSH) response necessary to buffer rising ROS and
prevent cellular damage. We report that GSH is essential for T cell effector
functions through its regulation of metabolic activity. Conditional gene
targeting of the catalytic subunit of glutamate cysteine ligase (Gclc) blocked
GSH production specifically in murine T cells. Gclc-deficient T cells initially
underwent normal activation but could not meet their increased energy and
biosynthetic requirements. GSH deficiency compromised the activation of mammalian
target of rapamycin-1 (mTOR) and expression of NFAT and Myc transcription
factors, abrogating the energy utilization and Myc-dependent metabolic
reprogramming that allows activated T cells to switch to glycolysis and
glutaminolysis. In vivo, T-cell-specific ablation of murine Gclc prevented
autoimmune disease but blocked antiviral defense. The antioxidative GSH pathway
thus plays an unexpected role in metabolic integration and reprogramming during
inflammatory T cell responses.
PMID- 28423343
TI - Chitosan as coagulant on cyanobacteria in lake restoration management may cause
rapid cell lysis.
AB - Combining coagulant and ballast to remove cyanobacteria from the water column is
a promising restoration technique to mitigate cyanobacterial nuisance in surface
waters. The organic, biodegradable polymer chitosan has been promoted as a
coagulant and is viewed as non-toxic. In this study, we show that chitosan may
rapidly compromise membrane integrity and kill certain cyanobacteria leading to
release of cell contents in the water. A strain of Cylindrospermopsis raciborskii
and one strain of Planktothrix agardhii were most sensitive. A 1.3 h exposure to
a low dose of 0.5 mg l-1 chitosan already almost completely killed these cultures
resulting in release of cell contents. After 24 h, reductions in PSII
efficiencies of all cyanobacteria tested were observed. EC50 values varied from
around 0.5 mg l-1 chitosan for the two sensitive strains, via about 5 mg l-1
chitosan for an Aphanizomenon flos-aquae strain, a toxic P. agardhii strain and
two Anabaena cylindrica cultures, to more than 8 mg l-1 chitosan for a
Microcystis aeruginosa strain and another A. flos-aquae strain. Differences in
sensitivity to chitosan might be related to polymeric substances that surround
cyanobacteria. Rapid lysis of toxic strains is likely and when chitosan flocking
and sinking of cyanobacteria is considered in lake restoration, flocculation
efficacy studies should be complemented with investigation on the effects of
chitosan on the cyanobacteria assemblage being targeted.
PMID- 28423342
TI - A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via
a Long, Rigidified, and Anionic beta-Hairpin Structure.
AB - Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are
prophylactic and therapeutic agents. Some of the most potent bnAbs target a
quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using
cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145,
in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated
between glycans at the trimer 3-fold axis, to contact peptide residues from all
three Env protomers, and thus explains its highly trimer-specific nature. Somatic
hypermutation in the other CDRs of PGT145 were crucially involved in stabilizing
the structure of the HCDR3, similar to bovine antibodies, to aid in recognition
of a cluster of conserved basic residues hypothesized to facilitate trimer
disassembly during viral entry. Overall, the findings exemplify the creative
solutions that the human immune system can evolve to recognize a conserved motif
buried under a canopy of glycans.
PMID- 28423344
TI - Prolonged dark period modulates the oxidative burst and enzymatic antioxidant
systems in the leaves of salicylic acid-treated tomato.
AB - Salicylic acid (SA) is an important plant growth regulator playing a role in the
hypersensitive reaction (HR) and the induction of systemic acquired resistance.
Since the SA-mediated signalling pathways and the formation of reactive oxygen
species (ROS) are light-dependent, the time- and concentration-specific induction
of oxidative stress was investigated in leaves of tomato plants kept under light
and dark conditions after treatments with 0.1mM and 1mM SA. The application of
exogenous SA induced early superoxide- and H2O2 production in the leaves, which
was different in the absence or presence of light and showed time- and
concentration-dependent changes. 1mM SA, which induced HR-like cell death
resulted in two peaks in the H2O2 production in the light but the first, priming
peak was not detected in the dark. Unlike 0.1mM SA, 1mM SA application induced
NADPH oxidase activity leading to increased superoxide production in the first
hours of SA treatments in the light. Moreover, SA treatments inhibited catalase
(CAT) activity and caused a transient decline in ascorbate peroxidase (APX), the
two main enzymes responsible for H2O2 degradation, which led to a fast H2O2 burst
in the light. Their activity as well as the expression of some isoenzymes of SOD
and APX increased only from the 12th h in the illuminated samples. The activity
of NADPH oxidase and expression SlRBOH1 gene encoding a NADPH oxidase subunit was
much lower in the dark. In spite of low CAT and APX activity after SA treatments
in the dark, the activation of guaiacol-dependent peroxidase (POD) could
partially substitute H2O2 scavenging activity of these enzymes in the dark, which
reduced the ROS burst and development of lesion formation in the leaves.
PMID- 28423348
TI - A neurorestorative approach to Parkinson's disease.
PMID- 28423349
TI - M channels and stress response.
PMID- 28423350
TI - ATXN2 a culprit with multiple facets.
PMID- 28423351
TI - Significance of inflammation-based indices in the prognosis of patients with non
metastatic colorectal cancer.
AB - Previous studies demonstrated that several inflammation-based hematological
indices are closely related to various malignancies, including colorectal cancer
(CRC). In this study, the prognostic value of inflammation-based markers,
including a combination index termed coNLR-PDW, comprising the preoperative
neutrophil-to-lymphocyte ratio (NLR) and the platelet distribution width (PDW),
was evaluated in 206 patients with non-metastatic CRC treated with surgery at a
single medical center. The association of patient demographics, blood chemistry,
and serum biochemical indices with recurrence-free survival (RFS) and overall
survival (OS) were examined through univariate and multivariate analysis.
Receiver operating characteristic curve analysis revealed the optimal cut-off
values of the NLR and lymphocyte-to-monocyte ratio (LMR) to be, respectively, 2.0
and 3.32 for both RFS and OS. For PDW, cut-off values of 17.25% and 17.35% were
defined for RFS and OS, respectively. On univariate analysis, lymph node
involvement, stage, presence of intravascular emboli (IVE), carbohydrate antigen
199 (CA199) >= 35 kU/L, NLR >= 2.0, LMR <= 3.32, elevated PDW, a high coNLR-PDW
score, high blood glucose, and high neutrophil and lymphocyte percentages
correlated with poorer RFS and OS (P < 0.05). On multivariate analysis, lymph
node involvement, IVE, CA199, PDW, and coNLR-PDW correlated with both RFS and OS
(P < 0.05), while NLR correlated only with OS (P = 0.001). These results
highlight the usefulness of the coNLR-PDW index as a prognostic marker of non
metastatic CRC outcome. In clinical practice, its assessment could contribute to
establishing more personalized regimes for patients undergoing tumor resection
surgery.
PMID- 28423352
TI - Prospective serum metabolomic profile of prostate cancer by size and extent of
primary tumor.
AB - Two recent investigations found serum lipid and energy metabolites related to
aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate
whether those metabolomic profiles represent etiologic or tumor biomarker
signals, we prospectively examined serum metabolites of prostate cancer cases by
size and extent of primary tumors in a nested case-control analysis in the ATBC
Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4
(n = 15) disease to controls (n = 200). Time from fasting serum collection to
diagnosis averaged 10 years (range 1-20). LC/MS-GC/MS identified 625 known
compounds, and logistic regression estimated odds ratios (ORs) associated with
one-standard deviation differences in log-metabolites. N-acetyl-3
methylhistidine, 3-methylhistidine and 2'-deoxyuridine were elevated in men with
T2 cancers compared to controls (ORs = 1.38-1.79; 0.0002 <= p <= 0.01). By
contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl
linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and
inositol 1-phosphate (ORs = 0.49-0.60; 0.000017 <= p <= 0.003). Secondary bile
acid lipids, sex steroids and caffeine-related xanthine metabolites were
elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with
T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit
qualitatively different metabolite profiles years in advance of diagnosis that
may represent etiologic factors, molecular patterns reflective of distinct
primary tumors, or a combination of both.
PMID- 28423353
TI - Silencing PRDM14 expression by an innovative RNAi therapy inhibits stemness,
tumorigenicity, and metastasis of breast cancer.
AB - PR domain zinc finger protein 14 (PRDM14) maintains stemness in embryonic stem
cells via epigenetic mechanisms. Although PRDM14 is elevated in several cancers,
it is unclear if and how PRDM14 confers stem cell-like properties and epigenetic
changes to cancer cells. Here, we examined the phenotypic characteristics and
epigenetic and gene expression profiles of cancer cells that differentially
express PRDM14, and assessed the potential of PRDM14-targeted cancer therapy.
PRDM14 expression was markedly increased in many different cancer types and
correlated with poor survival of breast cancer patients. PRDM14 conferred stem
cell-like phenotypes to cancer cells and regulated the expression of genes
involved in cancer stemness, metastasis, and chemoresistance. PRDM14 also reduced
the methylation of proto-oncogene and stemness gene promoters and PRDM14-binding
regions were primarily occupied by histone H3 Lys-4 trimethylation (H3K4me3),
both of which are positively correlated with gene expression. Moreover, strong
PRDM14 binding sites coincided with promoters containing both H3K4me3 and
H3K27me3 histone marks. Using calcium phosphate hybrid micelles as an RNAi
delivery system, silencing of PRDM14 expression by chimera RNAi reduced tumor
size and metastasis in vivo without causing adverse effects. Conditional loss of
PRDM14 function also improved survival of MMTV-Wnt-1 transgenic mice, a
spontaneous model of murine breast cancer. Our findings suggest that PRDM14
inhibition may be an effective and novel therapy for cancer stem cells.
PMID- 28423354
TI - CD54+ rabbit adipose-derived stem cells overexpressing HIF-1alpha facilitate
vascularized fat flap regeneration.
AB - Fat flap transplantation is frequently performed in patients suffering from soft
tissue defects resulting from disease or trauma. This study explored the
feasibility of constructing vascularized fat flaps using rabbit adipose-derived
stem cells (rASCs) and collagen scaffolds in a rabbit model. We evaluated rASCs
proliferation, paracrine function, adipogenesis, vascularization, and CD54
expression, with or without HIF-1alpha transfection in vitro and in vivo. We
observed that adipogenic differentiation potential was greater in rASCs with high
CD54 expression (CD54+rASCs) than in those with low expression (CD54-rASCs), both
in vitro and in vivo. HIF-1alpha overexpression not only augmented this effect,
but also enhanced cell proliferation and paracrine function in vitro. We also
demonstrated that HIF-1alpha-transfected CD54+rASCs showed enhanced paracrine
function and adipogenic capacity, and that paracrine function increases
expression of angiogenesis-related markers. Thus, CD54+rASCs overexpressing HIF
1alpha enhanced large volume vascularized fat flap regeneration in rabbits,
suggesting CD54 may be an ideal candidate marker for ASCs adipogenic
differentiation.
PMID- 28423355
TI - Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells
and promote angiogenesis.
AB - Mesenchymal stem cells (MSCs) have been found to benefit patients with a variety
of ischemic diseases via promoting angiogenesis. It is also well established that
exosomes secreted from MSCs deliver bioactive molecules, including microRNAs
(miRs) to recipient cells. Therefore, we hypothesized that exosomes secreted from
MSCs deliver miRs into endothelial cells and mediate angiogenesis. The pro
angiogenic stimulatory capacity of exosomes was investigated using tube-like
structure formation and spheroid-based sprouting of human umbilical vein
endothelial cells (HUVECs), and in vivo Matrigel plug assay. The secretion of pro
angiogenic miRs (pro-angiomiRs) from MSCs into culture medium and transfer of the
miRs to HUVECs were confirmed using real-time quantitative PCR. Supplementation
of the exosome secretion blocker GW4869 (10 MUM) reduced the pro-angiomiRs in the
MSC-derived conditioned medium (CdMMSC). Addition of exosomes isolated from
CdMMSC could directly 1) promote HUVEC tube-like structure formation in vitro; 2)
mobilize endothelial cells into Matrigel plug subcutaneously transplanted into
mice; and 3) increase blood flow inside Matrigel plug. Fluorescence tracking
showed that the exosomes were internalized rapidly by HUVECs causing an
upregulated expression of pro-angiomiRs in HUVECs. Loss-and-gain function of the
pro-angiomiRs (e.g., miR-30b) in MSCs significantly altered the pro-angiogenic
properties of these MSC-derived exosomes, which could be associated with the
regulation of their targets in HUVECs. These results suggest that exosomal
transfer of pro-angiogenic miRs plays an important role in MSC mediated
angiogenesis and stem cell-to-endothelial cell communication.
PMID- 28423356
TI - Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by
promoting the formation of Apaf-1-caspase-9 complex.
AB - MicroRNAs have been proved to participate in multiple biological processes in
cancers. For developing resistance to cytotoxic drug, cancer cells, especially
the cancer stem cells, usually change their microRNA expression profile to
survive in hostile environments. In the present study, we found that expression
of microRNA-27a was increased in colorectal cancer stem cells. High level of
microRNA-27a was indicated to induce the resistance to TNF-related apoptosis
inducing ligand (TRAIL). Knockdown of microRNA-27a resensitized colorectal cancer
stem cells to TRAIL-induced cell death. Mechanically, the gene of Apaf-1, which
is associated with the mitochondrial apoptosis, was demonstrated to be the target
of microRNA-27a in colorectal cancer stem cells. Knockdown of microRNA-27a
increased the expression level of Apaf-1, thus enhancing the formation of Apaf-1
caspase-9 complex and subsequently promoting the TRAIL-induced apoptosis in
colorectal cancer stem cells. These findings suggested that knockdown of microRNA
27a in colorectal cancer stem cells by the specific antioligonucleotides was
potential to reverse the chemoresistance to TRAIL. It may represent a novel
therapeutic strategy for treating the colorectal cancer more effectively.
PMID- 28423357
TI - MiR-29b inhibits the growth of glioma via MYCN dependent way.
AB - MiR-29b is widely involved in diverse cancers. We plan to study its role in
glioma. The expression of miR-29b was detected by real-time polymerase chain
reaction (PCR) and we found the expression of miR-29b was decreased in glioma.
Cell proliferation was evaluated by cell counting kit (CCK8) and 5-Ethynyl-2'-
deoxyuridine (EdU) and cell apoptosis was assayed with flow cytometry assay
(FCA), which indicated miR-29b can inhibit the proliferation and promote the
apoptosis of glioma cells. The target of miR-29b was predicted using miRanda,
TargetScan and PicTar sofeware and we also found MYCN was a direct target of miR
29b in glioma cells and miR-29b inhibited the proliferation of glioma cells via
MYCN dependent way. Subcutaneous xenotransplantation model was designed to
investigate the affection of miR-29b on glioma growth. The effectiveness of miR
29b for glioma prediction was also performed and we determined miR-29b can stably
exist and may act as a biomarker for the diagnosis of glioma. As a conclusion,
miR-29b inhibits the growth of glioma via MYCN dependent way and can be a
biomarker for the diagnosis of glioma.
PMID- 28423358
TI - Characterization of fusion genes in common and rare epithelial ovarian cancer
histologic subtypes.
AB - Gene fusions play a critical role in some cancers and can serve as important
clinical targets. In epithelial ovarian cancer (EOC), the contribution of
fusions, especially by histological type, is unclear. We therefore screened for
recurrent fusions in a histologically diverse panel of 220 EOCs using RNA
sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to
identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA)
tumors. Associations between fusions and clinical prognosis were evaluated using
Cox proportional hazards regression models. Nine recurrent fusions, defined as
occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most
frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This
fusion was not associated with survival; other recurrent fusions were too rare to
warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique
to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some
evidence that CC tumors harbor more fusions on average than any other EOC
histological type, including high-grade serous (HGS) tumors. CC tumors harbored a
mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC
tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in
endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean =
0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10%
frequency in the CC EOC subtype, but find little evidence for common (> 5%
frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC
tumors.
PMID- 28423359
TI - Epithelial-mesenchymal transition induced by GRO-alpha-CXCR2 promotes bladder
cancer recurrence after intravesical chemotherapy.
AB - Non-muscle invasive bladder cancers (NMIBC) are typically treated by
transurethral resection with intravesical chemotherapy. However, the post
therapeutic incidence of tumor recurrence and progression to muscle invasive
disease is high, and the underlying mechanism(s) remains unknown. In this study,
we observed that recurrent bladder cancer cells exhibit a mesenchymal phenotype,
which is initiated by the autocrine GRO-alpha signaling. Mechanically, the
chemotherapeutic drug epidoxorubicin induces GRO-alpha expression in primary
bladder cancer cells at G1/S phase via p38-dependent activation of NF-kappaB. GRO
alpha phosphorylation of Snail on Ser246 supports Snail's accumulation in the
nucleus, and thereby promotes transcription repression activity of Snail from E
cadherin promoters. In accordance, disrupting the GRO-alpha-Snail axis in NMIBC
represents a promising alternative to prevent post-therapeutic tumor progression
and recurrence.
PMID- 28423360
TI - TIAM1 variants improve clinical outcome in neuroblastoma.
AB - Identification of tumor driver mutations is crucial for improving clinical
outcome using a personalized approach to the treatment of cancer. Neuroblastoma
is a tumor of the peripheral sympathetic nervous system for which only a few
driver alterations have been described including MYCN amplification and ALK
mutations. We assessed 106 primary neuroblastoma tumors by next generation
sequencing using a customized amplicon-based gene panel. Our results reveal that
genetic variants in TIAM1 gene associate with better clinical outcome, suggesting
a role for these TIAM1 variants in preventing progression of this disease. The
detected variants are located within the different domains of TIAM1 that signal
to the upstream regulator RAS and downstream effector molecules MYC and RAC,
which are all implicated in neuroblastoma etiology and progression. Clinical
outcome was improved in tumors where a TIAM1 variant was present concomitantly
with either ALK mutation or MYCN amplification. Given the function of these
signaling molecules in cell survival, proliferation, differentiation and neurite
outgrowth, our data suggest that the TIAM1-mediated network is essential to
neuroblastoma and thus, inhibiting TIAM1 reflects a rational strategy for
improving therapy efficacy in neuroblastoma.
PMID- 28423361
TI - Next-generation sequencing reveals microRNA markers of adrenocortical tumors
malignancy.
AB - BACKGROUND: Adrenocortical carcinoma is a rare finding among common
adrenocortical tumors, but it is highly aggressive and requires early detection
and treatment. Still, the differential diagnosis between benign and malignant
lesions is difficult even for experienced pathologists and there is a significant
need for novel diagnostic methods. In this study we aimed to reveal a complete
set of microRNAs expressed in the adrenal gland and to identify easily
detectable, stable and objective biomarkers of adrenocortical malignancy.
METHODS: We employed next-generation sequencing to analyze microRNA profiles in a
unique set of 51 samples, assigned to either a learning dataset including 7
adrenocortical carcinomas (ACCs), 8 adrenocortical adenomas (AAs) and 8 control
samples (NAs), or a validation dataset including 8 ACCs, 10 AAs and 10 NAs. The
results were validated in real-time Q-PCR. RESULTS: We detected 411 miRNAs
expressed in 1763 length isoforms in the examined samples. Fifteen miRNAs
differentiate between malignant (ACC) and non-malignant (AA + NA) tissue in the
test set of independent samples. Expression levels of 6 microRNAs, miR-503-5p,
miR-483-3p, miR-450a-5p, miR-210, miR-483-5p, miR-421, predict sample status
(malignancy/non-malignancy) with at least 95% accuracy in both datasets. The best
single-gene malignancy marker, miR-483-3p, has been validated by real-time RT
PCR. CONCLUSIONS: As a result of the study we propose clinically valid and easily
detectable biomarkers of adrenocortical malignancy that may significantly
facilitate morphological examination. Since microRNAs can be detected in blood,
the study brings tools for development of non-invasive diagnostics of
adrenocortical carcinomas.
PMID- 28423362
TI - TROP2 promotes proliferation, migration and metastasis of gallbladder cancer
cells by regulating PI3K/AKT pathway and inducing EMT.
AB - The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many
cancers. However, its effect on proliferation, migration and metastasis of
gallbladder cancer remains unclear. In this study, we found that TROP2 was highly
expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor
prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited
the cell proliferation, clone formation, invasion and migration in vitro, while
TROP2 overexpression had opposite effects. In addition, knockdown of TROP2
increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via
PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E
cadherin expression during epithelial-mesenchymal transition (EMT). Moreover,
gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors
in vivo. In consistent with in vitro results, TROP2 inhibition decreased Akt
phosphorylation, increased PTEN expression and postponed EMT of gallbladder
cancer cells in vivo. In conclusion, we revealed that TROP2 promoted the
proliferation, migration and metastasis of gallbladder cancer cells by regulating
PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic
biomarker and therapeutic target for the clinical management of gallbladder
cancer.
PMID- 28423363
TI - Multiple-gene panel analysis in a case series of 255 women with hereditary breast
and ovarian cancer.
AB - As new genes predisposing to breast (BC) and ovarian cancer (OC) are constantly
emerging, the use of panels of genes analyzed by Next-Generation Sequencing (NGS)
is increasing in clinical diagnostics. The identification of a large number of
new germline mutations allows for deeper knowledge of cancer predisposition,
although raising many questions about patient management.BC and OC patients
recruited by our counseling service between 2012-2015 were included in this
study. DNA was extracted from peripheral blood and a panel of 94 genes involved
in hereditary tumors was analyzed by NGS. Patient clinical features of BC and OC
and cancer family history were collected and compared to the patient genetic
profile.A total of 255 women were analyzed, 57 of whom had a pathogenic mutation
in BRCA1/2 genes, and 17 carried pathogenic mutations in other genes, such as
PALB2, ATM, BRIP1, RAD51D, MSH6, PPM1D, RECQL4, ERCC3, TSC2, SLX4 and other
Fanconi anemia genes.Patients with a pathogenic mutation in genes other than
BRCA1 and BRCA2 showed no significant difference from the BRCA1/2-mutated
carriers with respect to age at diagnosis and clinical features, suggesting that
mutations in other genes could pose a high risk of cancer development.These
patients had a much higher percentage of bilateral breast cancer (BBC) and a
lower rate of OC than BRCA-mutated patients and patients with no pathogenic
mutations: as a consequence, the surveillance protocol should be customized to
the patient genetic characteristics.
PMID- 28423364
TI - Increased expression of deleted in malignant brain tumors (DMBT1) gene in
precancerous gastric lesions: Findings from human and animal studies.
AB - Helicobacter pylori infection triggers a cascade of inflammatory stages that may
lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal
metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1)
belongs to the group of secreted scavenger receptor cysteine-rich proteins and is
considered to be involved in host defense by binding to pathogens. Initial
studies showed its deletion and loss of expression in a variety of tumors but the
role of this gene in tumor development is not completely understood. Here, we
examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African
American and Hispanic individuals as well as in the development of gastric
pathology in a mouse model of H. pylori infection. We found that in 3 different
populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in
individuals with dysplasia compared to multifocal atrophic gastritis without
intestinal metaplasia; the increase was also observed in individuals with
advanced gastritis and positive H. pylori infection. In our animal model, H.
pylori infection of Dmbt1-/- mice resulted in significantly higher levels of
gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in
the gastric mucosa compared to H. pylori-infected wild type mice. Our data in the
animal model suggest that in response to H. pylori infection DMBT1 may mediate
mucosal protection reducing the risk of developing gastric precancerous lesions.
However, the increased expression in human gastric precancerous lesions points to
a more complex role of DMBT1 in gastric carcinogenesis.
PMID- 28423365
TI - Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival of
epithelial ovarian cancer: a systematic review and meta-analysis of observational
studies.
AB - Inflammation plays an important role in the development and progression of
epithelial ovarian cancer (EOC). However, no meta-analysis has comprehensively
and quantitatively investigated the prognostic value of the neutrophil-to
lymphocyte ratio (NLR) in EOC patients. Therefore, we performed a meta-analysis
to quantify the prognostic impact of this biomarker. We searched the PubMed and
Web of Science databases from their inception through December 31, 2016, and
examined observational studies evaluating the association of preoperative NLR
with progression-free survival (PFS) and overall survival (OS) of EOC patients. A
random-effects model was used to summarize hazard ratios (HRs) with 95%
confidence intervals (CIs). Twelve retrospective cohort studies including 3,154
EOC patients were identified. Elevated NLR in EOC patients was associated with
worse PFS (summarized HR=1.80; 95% CI = 1.22-2.65; I2 = 79.1%) and OS (summarized
HR = 1.72; 95% CI = 1.18-2.51; I2 = 73.5%) compared with low NLR. No evidence of
publication bias was detected by funnel plot analysis and formal statistical
tests. Although the results were robust in all subgroup analyses, not all results
were statistically significant. We determined that adjustments for CA-125 level
and performance status might be sources of heterogeneity. These combined results
indicate that preoperative NLR is an important predictor of prognosis in EOC
patients. Since the high heterogeneity and retrospective study design of included
studies, these results require further validation with prospective cohort and
trials enrolling larger patient populations and conducting longer follow-up
examinations.
PMID- 28423366
TI - Legume intake and risk of prostate cancer: a meta-analysis of prospective cohort
studies.
AB - Previous studies regarding the relationship between legume intake and risk of
prostate cancer have reported inconsistent results. We conducted a meta-analysis
of prospective cohort studies to summarize evidence on this association. A
systematic literature search of articles published through June 2016 was
performed using PubMed and Web of Science databases. The combined relative risk
(RR) with its 95% confidence interval (CI) for the highest versus the lowest
intake of legumes was calculated with a random-effects model. Dose-response meta
analysis was also performed for the studies that provided at least three levels
of legume consumption. Ten articles (eight cohorts) reporting 281,034 individuals
and 10,234 incident cases were identified. The individuals with high consumption
of legumes compared with the reference group experienced a significantly reduced
risk for developing prostate cancer (RR: 0.85 [95% CI 0.75-0.96], P = 0.010).
Moderate heterogeneity of RRs was observed across these studies (P = 0.064 for
heterogeneity, I2 = 45.8 %). Dose-response meta-analysis indicated that the risk
of prostate cancer reduced by 3.7% (95% CI 1.5%-5.8%) for each 20 grams per day
increment of legume intake. In conclusion, the results from this meta-analysis
suggest that a high intake of legumes is associated with a low incidence of
prostate cancer.
PMID- 28423368
TI - The effects of herbal medicine on epilepsy.
AB - Traditional herbal medicine plays a significant role in the treatment of
epilepsy. Though herbal medicine is widely used in antiepileptic treatment, there
is a lack of robust evidence for efficacy and toxicity of most herbs. Besides,
the herbal medicine should be subject to evidence-based scrutiny. In this
context, we present a review to introduce the effects of herbal medicine on
epilepsy. However, hundreds of herbal medicines have been investigated in the
available studies. Some commonly used herbal medicines for epilepsy have been
listed in our study. The overwhelming majority of these data are based on animal
experiments. The lack of clinical data places constraints on the clinical
recommendation of herbal medicine. Our study may conduct further studies and
provide some insight on the development of anti-epileptic drugs.
PMID- 28423369
TI - MDI 301, a synthetic retinoid, depressed levels of matrix metalloproteinases and
oxidative stress in diabetic dermal fibroblasts.
AB - Diabetic foot ulcerations could result in serious consequences such as
amputations. The up-regulation of matrix metalloproteinases and down-regulation
of TIMP1 were remarked as distinctive biological characteristics in the diabetic
dermal fibroblast. The current study was performed in order to clarify the effect
of high glucose on formation of diabetic dermal fibroblast cell. In addition, the
effect of MDI 301 on ameliorating diabetic fibroblasts was investigated in this
study. The mRNA and protein expression levels of MMPs, TIMP1 and catalase were
evaluated against fibroblasts treated with high glucose (30 mM) using qRT-PCR,
western blotting and zymography assays. Methods were also employed for
investigating the biological effects of MDI 301 on high glucose-induced diabetic
fibroblasts. In this study, we found that the unbalance of oxidative stress
induced by high glucose concentration play an important role in the formation of
diabetic dermal fibroblast from normal cells. In addition, MDI 301, a picolinic
acid-substituted ester of 9-cis retinoic acid was employed in this study in order
to ameliorate symptoms on diabetic dermal fibroblast induced by high glucose
concentration. We found MDI 301 alleviate the effects of high glucose-induced
skin damage by balancing the oxidative stress and regulating the MMPs and TIMP1
levels. Our finding indicated that MDI 301 offers the potential for repairing the
faulty skin function arising from diabetes.
PMID- 28423370
TI - Transarterial chemoembolization combined with Jie-du granule preparation improves
the survival outcomes of patients with unresectable hepatocellular carcinoma.
AB - The aim of the present study was to compare the effectiveness of transarterial
chemoembolization (TACE), TACE combined with Jie-du granules (JD), and TACE
combined with sorafenib (SOR) for treating patients with unresectable
hepatocellular carcinoma (HCC). For this purpose, we conducted a retrospective
analysis of data from 266 consecutive patients with unresectable HCC who
underwent TACE treatment at the Shanghai Hospital and Eastern Hepatic Surgery
Hospital between Jan 2009 and Dec 2010. We prospectively analyzed patient
survival and progression times as well as independent predictors, within a follow
up period of 86 months. Patients were divided into TACE-JD (n = 75), TACE-SOR (n
= 124) and TACE (n = 67) groups. Median overall survival (OS) times being: TACE
JD, 21.43 months; TACE-SOR, 23.23 months; TACE, 13.97 months (TACE-SOR vs TACE, P
< 0.001; TACE-SOR vs TACE-JD, P = 0.852; TACE-JD vs TACE, P < 0.001). The median
times to progression (TTP) were as follows: TACE-JD, 8.67 months; TACE-SOR, 5.37
months; TACE, 4.57 months (TACE-SOR vs TACE, P = 0.479; TACE-SOR vs TACE-JD, P <
0.001; TACE-JD vs TACE, P < 0.001). Independent predictors of OS were treatment
allocation, Child-Pugh class large tumor, albumin and extrahepatic metastasis.
These findings show that patients with unresectable HCC who were administered
TACE-JD survived significantly longer compared with those administered TACE or
TACE-SOR.
PMID- 28423371
TI - Subjective Technology Adaptivity Predicts Technology Use in Old Age.
AB - BACKGROUND: To date, not much is known about the psychological and motivational
factors underlying technology use in late life. What are the interindividual
determinants that lead older adults to invest in using technological innovations
despite the age-related physiological changes that impose challenges on
behavioral plasticity in everyday life? OBJECTIVE: This research explores
interindividual differences in subjective technology adaptivity - a general
technology-related motivational resource that accounts for technology use in late
life. More specifically, we investigate the influence of this factor relative to
demographic characteristics, personality traits, and functional limitations in a
longitudinal sample of community-dwelling older adults. METHODS: We report
results from a paper-and-pencil survey with 136 older adults between 59 and 92
years of age (mean = 71.4, SD = 7.4). Of those participants, 77 participated in a
2-year follow-up. We assessed self-reports of technology use, subjective
technology adaptivity, functional limitations, and the personality traits
openness to new experiences and neuroticism. RESULTS: Higher levels of subjective
technology adaptivity were associated with technology use at the first
measurement as well as increased use over the course of 2 years. CONCLUSIONS:
Subjective technology adaptivity is a significant predictor of technology use in
old age. Our findings contribute to improving the understanding of
interindividual differences when using technological innovation in late life.
Moreover, our findings have implications in the context of user involvement and
may contribute to the successful development of innovative technology for older
adults.
PMID- 28423372
TI - Patterns of Disease in Patients with Middle-Lobe Predominant Bronchiectasis.
AB - BACKGROUND: Middle-lobe predominant bronchiectasis affecting the right middle
lobe and/or lingula (RMLP) is classically described in asthenic, elderly females
with skeletal abnormalities or associated nontuberculous mycobacterial (NTM)
infection. OBJECTIVES: We aimed to evaluate the frequency and clinical
characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed
bronchiectasis patients and determine associations with disease severity.
METHODS: A retrospective observational cross-sectional cohort study of
consecutive bronchiectasis patients in our institution was performed. Data were
collected on baseline variables, microbiology status, lung function, and
radiology according to the modified Bhalla score. Disease severity was assessed
using bronchiectasis severity index (BSI) and FACED severity scores. RESULTS: Of
81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20
(24.7%) had RMLP disease. These patients were significantly younger, female, and
with lower BMIs than patients with the classical bronchiectasis phenotype (p =
0.03, 0.01, and p <0.01, respectively). Fewer symptoms of cough and daily sputum
(p = 0.01 and <0.01), prior exacerbation frequency (p = 0.03), and higher
baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of
NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in
RMLP patients were significantly lower than their counterparts (both p < 0.001).
CONCLUSIONS: The RMLP phenotype is associated with younger patients than
classically described in the literature. An increased rate of NTM infection in
this phenotype was noted, particularly in females, but much lower than previously
described. Lung function and disease severity scores in this patient group are
relatively normal, suggesting a milder phenotype in patients with this form of
the disease.
PMID- 28423373
TI - Distribution of Interstitial Telomeric Sequences in Primates and the Pygmy Tree
Shrew (Scandentia).
AB - It has been hypothesized that interstitial telomeric sequences (ITSs), i.e.,
repeated telomeric DNA sequences found at intrachromosomal sites in many
vertebrates, could be correlated to chromosomal rearrangements and plasticity. To
test this hypothesis, we hybridized a telomeric PNA probe through FISH on
representative species of 2 primate infraorders, Strepsirrhini (Lemur catta,
Otolemur garnettii, Nycticebus coucang) and Catarrhini (Erythrocebus patas,
Cercopithecus petaurista, Chlorocebus aethiops, Colobus guereza), as well as on 1
species of the order Scandentia, Tupaia minor, used as an outgroup for primates
in phylogenetic reconstructions. In almost all primate species analyzed, we found
a telomeric pattern only. In Tupaia, the hybridization revealed many bright ITSs
on at least 11 chromosome pairs, both biarmed and acrocentric. These ITS signals
in Tupaia correspond to fusion points of ancestral human syntenic associations,
but are also present in other chromosomes showing synteny to only a single human
chromosome. This distribution pattern was compared to that of the heterochromatin
regions detected through sequential C-banding performed after FISH. Our results
in the analyzed species, compared with literature data on ITSs in primates,
allowed us to discuss different mechanisms responsible for the origin and
distribution of ITSs, supporting the correlation between rearrangements and ITSs.
PMID- 28423374
TI - Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden
Sensorineural Hearing Loss after Failure of Systemic Steroids.
AB - We evaluated the outcomes of and prognostic factors for idiopathic sudden
sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen
therapy (HBOT). A retrospective review of clinical data was performed for 167
patients with ISSNHL who failed to respond to systemic steroids and were treated
by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical
outcomes, the averaged 5-frequency hearing level after systemic steroids, patient
age, the interval between post-steroids and pre-HBOT, vertigo as a complication,
the presence of diabetes mellitus, smoking history, and hypertension. Overall,
after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with
definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The
overall rate of hearing improvement was higher in the study group (77/167 cases,
46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed
appropriately, HBOT should be able to improve hearing in many cases unresponsive
to initial therapy.
PMID- 28423375
TI - Evaluation of Short-Term Efficacy of Concurrent Chemoradiotherapy in Primary
Fallopian Tube Carcinoma by Diffusion-Weighted Imaging: A Retrospective Study.
AB - BACKGROUND: This study aims to evaluate the short-term efficacy of concurrent
chemoradiotherapy (CCRT) in primary fallopian tube carcinoma (PFTC) using
magnetic resonance diffusion-weighted imaging (MR-DWI). PATIENTS AND METHODS:
Total abdominal irradiation was performed for 61 PFTC patients after surgery, and
paclitaxel and carboplatin were used for CCRT. According to the response
evaluation criteria in solid tumors (RECIST1.1), patients were divided into a
sensitive (n = 36) and a resistant group (n = 25). Pearson correlation analysis
was conducted to assess the correlations of tumor regression rate with apparent
diffusion coefficient (ADC)pre, ADCpost, and ?ADCpost. The efficacy of CCRT in
PFTC using MR-DWI was evaluated by ROC curve, logistic regression analysis,
Kaplan-Meier survival curve, and Cox regression model. RESULTS: The ADCpre in
both the sensitive and the resistant group was negatively associated with the
tumor regression rate (r = -0.508), while the ADCpost (r = 0.454) and ?ADCpost (r
= 0.769) were positively associated with the tumor regression rate (all p <
0.05). Histopathological type, FIGO stage, lymphatic metastasis, tumor regression
rate, ADCpre, ADCpost, and ?ADCpost were confirmed as key factors for CCRT in
PFTC (all p < 0.05). CONCLUSION: Our retrospective study demonstrates the
predictive value of MR-DWI in CCRT for PFTC patients.
PMID- 28423376
TI - Controlled Pressure: The Solution for a High-Pressure Situation - Aetiology and
Techniques for Control of Airway Haemorrhage.
PMID- 28423377
TI - Risk and Survival of Patients with Head and Neck Cutaneous Melanoma: National
Perspective.
AB - OBJECTIVE: Head and neck cutaneous melanoma represents a distinct entity of skin
cancer. We aim to examine management and survival of patients with head and neck
cutaneous melanoma. METHODS: A retrospective cohort study utilizing the National
Cancer Database, 2004-2012. RESULTS: A total of 20,322 (21.2%) head and neck
melanomas and 75,547 (78.8%) melanomas of other sites were included. The median
follow-up time of head and neck melanoma was 41.6 months (interquartile range:
22.9-68.2 months). Patients with melanoma of the head and neck were more likely
to be >=65 years old, male, and/or white (p < 0.001 each). Positive surgical
margin was more prevalent in head and neck melanoma [OR: 2.19, 95% CI: (2.03,
2.37)], and was associated with a lower survival [HR: 1.41, 95% CI: (1.28,
1.57)]. High positive lymph node ratio was associated with a lower survival [HR:
2.00, 95% CI: (1.13, 3.57)]. Adjuvant immunotherapy was associated with an
improved survival [HR: 0.67, 95% CI: (0.57, 0.80)]. CONCLUSION: Head and neck
cutaneous melanoma is associated with certain demographics. Surgical margin
status, lymph node ratio, and immunotherapy are independently associated with
overall survival.
PMID- 28423378
TI - Innovative Treatment Concepts for Cutaneous T-Cell Lymphoma Based on
Microenvironment Modulation.
AB - Cutaneous T-cell lymphomas (CTCL) are a rare and biologically heterogeneous
malignant entity comprising mycosis fungoides and Sezary syndrome as the most
common subtypes. The current treatment outcome is characterized by high rates of
relapse, but survival is usually not significantly shortened in low-stage
disease. This is different in tumor-stage disease or aggressive CTCL subtypes
where survival is significantly reduced. Recent advances have been made on
several levels of tumor biology: Whole genome sequencing has resulted in novel
strategies of NF-kappaB or JAK inhibition, ongoing translational research has
revealed new targets like CD30 or CCR4, and, finally, research focusing on
impaired immunosurveillance has gained more importance. Based on the growing
knowledge about the functional roles of the tumor microenvironment and non
malignant infiltrating cells, current research aims to develop novel CTCL
treatment strategies. This review focuses on the mounting evidence for
efficiently targeting tumor-infiltrating immune cells and thereby modulating the
tumor microenvironment and restoring immunosurveillance.
PMID- 28423379
TI - Excessive Weight Favours Skin Physiology - Up to a Point: Another Expression of
the Obesity Paradox.
AB - BACKGROUND/AIMS: Recently classified as an epidemic by the WHO, obesity (as well
as the state of being overweight) clearly affects significant populations across
all ages. The relationship between obesity and some diseases (e.g. cardiovascular
ones) is known, although many paradoxes remain to be explained. Very little
information is available, however, regarding its impact on skin physiology and
skin disease. This study aims to examine the influence of excessive weight on
epidermal hydration and transepidermal water loss, key variables of skin water
balance and skin biomechanics. METHODS: A convenience sample of 89 healthy female
volunteers was selected and divided into 4 groups, according to their BMI (body
mass index), as normal (control), overweight, obese (I and II), and morbid. Skin
physiology was quantitatively assessed in all individuals in 4 anatomical areas
using non-invasive biometrical analysis by reference instrumentation. Descriptive
and comparative statistics were applied, adopting a confidence level of 95%.
RESULTS: A non-linear alteration for all variables was detected as a function of
BMI. CONCLUSION: Results suggest that excessive weight might favour skin
performance within certain limits, reflecting a particular adaptation of the skin
to the weight gain and body contour.
PMID- 28423380
TI - A Systematic Review of Symptoms and Quality of Life Issues in Pancreatic
Neuroendocrine Tumours.
PMID- 28423381
TI - Self-Administered Tinnitus Pitch Matching versus a Conventional Audiometric
Procedure.
AB - OBJECTIVE: Obtaining an accurate tinnitus pitch match is an initial and critical
requirement for tinnitus evaluation and treatment, particularly for applying
tailor-made notched music training. We investigated whether computer-based self
administered tinnitus pitch matching (CSTPM) is comparable with a conventional
audiometric procedure (CAP). METHODS: In total, 82 patients (mean age 45.52
years; 42 females) with tonal tinnitus participated. The CAP was performed by the
same audiologist using a 2-alternative forced choice method with a frequency
range of 0.25-16 kHz. In the CSTPM, the subjects used personal computer software
with a scrolling slider to select the sound closest to their tinnitus pitch.
After each matching procedure, an octave challenge test was applied. A
multivariate logistic regression was performed to determine factors associated
with the difference between the CSTPM and CAP. RESULTS: The subjects' mean
hearing threshold was 21.25 +/- 17.61 dB HL; the mean tinnitus handicap inventory
score was 35.56 +/- 24.09. The mean pitches measured with the CSTPM and CAP were
6.29 +/- 4.30 and 6.98 +/- 5.33 kHz, respectively. In total, 57 (69.5%) subjects
matched their tinnitus with less than half an octave difference between the
procedures. The results of the 2 methods correlated significantly with each other
(Pearson r = 0.793, p < 0.001). Octave confusion was a significant factor
affecting the difference between the procedures (odds ratio 8.92, p < 0.05).
CONCLUSIONS: The CSTPM appears to be as accurate as the standard audiological
procedure, and may be used instead of the CAP when octave confusion is minimized.
PMID- 28423382
TI - Late Recurrence of Early Stage Cervical Cancer more than 3 Years after Radical
Hysterectomy with Pelvic Node Dissection.
AB - BACKGROUND: The aim of this study was to compare the clinicopathological
characteristics and outcomes of patients who developed late recurrence (> 3
years) of early stage cervical cancer after radical surgery with those of
patients who developed early recurrence (<= 3 years). We also investigated the
risk factors of late recurrence. METHODS: The records of 515 patients with early
stage cervical cancer diagnosed between 1999 and 2015 were reviewed. 53 patients
developed recurrence, 35 early and 18 late, and their clinicopathological
characteristics and outcomes were compared. Of the 515 patients, the records for
307 patients who remained tumor free for at least 3 years after radical surgery
were further examined. RESULTS: No significant differences were found in
clinicopathological characteristics and clinical outcomes between the early and
late recurrence groups with regard to age, stage, histology, tumor size,
lymphovascular space invasion, stromal invasion, parametrial involvement, node
status, vaginal margin, preoperative blood testing, adjuvant therapy, symptom
status at recurrence, site of recurrence and survival after recurrence. Late
recurrence was detected in 18 of the 307 patients (5.9%). Only node status and
deep stromal invasion (DSI) were independently associated with late recurrence.
CONCLUSION: Lymph node metastasis and DSI are risk factors for late recurrence.
Careful long-term follow-up is needed, particularly in cases with lymph node
metastasis and/or DSI.
PMID- 28423383
TI - Remarkable Advances in the Management of Mycosis Fungoides and the Sezary
Syndrome.
PMID- 28423384
TI - Cetuximab-Carboplatin-5-Fluorouracil Regimen in Elderly Patients with Recurrent
or Metastatic Head and Neck Squamous-Cell Carcinoma: A French Retrospective
Survey.
AB - BACKGROUND: The cetuximab plus platinum-based chemotherapy regimen is a standard
of care in the treatment of recurrent or metastatic head and neck squamous-cell
carcinoma (HNSCC). The feasibility in the elderly population is currently
unknown. METHODS: We performed a retrospective study in order to assess the
efficacy and safety of the cetuximab plus platinum-based chemotherapy regimen in
patients >65 years with recurrent or metastatic HNSCC. We performed a
retrospective review of all medical records from recurrent or metastatic HNSCC
patients >65 years treated with the cetuximab plus platinum-based chemotherapy
regimen between September 2008 and December 2013 in our institution (Centre Paul
Strauss, Strasbourg, France). RESULTS: A total of 59 patients were identified.
Carboplatin in combination with 5-fluorouracil (FU) was the only cetuximab
associated chemotherapy regimen used for treating elderly patients. The median
progression-free survival was 4 months (95% confidence interval [CI]: 2.9-4.7),
and the median overall survival was 9.1 months (95% CI: 6.5-13.1). Grade 3 or 4
toxicity adverse events occurred in 52% (n = 31) of the patients (mostly
hematologic toxicities and infections). CONCLUSIONS: This retrospective study
suggests that the cetuximab plus carboplatin-5FU chemotherapy is an effective
treatment option for elderly patients with recurrent or metastatic HNSCC.
PMID- 28423385
TI - Guidelines for the Management of Diabetic Macular Edema by the European Society
of Retina Specialists (EURETINA).
AB - Diabetic retinal disease is envisioned to become the plague of the coming decades
with a steep increase of worldwide diabetes incidence followed by a substantial
rise in retinal disease. Improvements in diagnostic and therapeutic care have to
cope with this dilemma in a clinically and socioeconomically efficient manner.
Laser treatment has found a less destructive competitor in pharmacological
treatments. As a consequence of recent rigorous clinical trials, laser
photocoagulation is no longer recommended for the treatment of diabetic macular
edema (DME), and anti-vascular endothelial growth factor therapy has emerged as
first-line therapy. Steroids have maintained a role in the management of
chronically persistent DME. The paradigm shifts in therapy are accompanied by a
substantial break-through in diagnostics. The following guidance for the
management of DME has been composed from the best updated knowledge of leading
experts in Europe and represents another volume in the series of EURETINA
recommendations for the management of retinal disease.
PMID- 28423386
TI - Early Longitudinal Spectral Domain Optical Coherence Tomography Findings in
Subacute Sclerosing Panencephalitis.
PMID- 28423387
TI - Optical Coherence Tomography Angiography of Retinal Cavernous Hemangioma.
PMID- 28423388
TI - A National Study of the Effect of Race, Socioeconomic Status, and Gender on Burn
Outcomes.
AB - Age, burn size, and inhalation injury are the major contributing variables
related to burn mortality. While the female gender has been linked to higher
mortality, the impact of socioeconomic status has not been well studied. The
interplay between these three factors is also unknown. This study sought to
clarify the effects of these variables on outcomes in a national sample of
patients with burns. A retrospective review of 172,640 patient records of the
National Burn Repository (version 8, 2002-2011) data was conducted. Of those
records, 36,960 (21.4%) patient entries were excluded for duplicate entries,
follow-up visits, readmissions, nonburn injuries, skin diseases, and
incompleteness (missing date of admission, date of discharge, race, or TBSA of
burn or TBSA). Univariate and multivariate analyses were performed to compare
outcomes by race (Caucasian, African-American, and other minority groups). P <
.05 was considered significant. The study group included 135,680 patients and was
predominately Caucasian (59.0% Caucasian, 19.0% African-American, and 22.0% other
minority groups). The African-American race had more females, operations, longer
length of stay, ventilator days, septicemia (all P < .001), and urinary tract
infections (UTIs, P < .01). Caucasians had the largest burns (9.27 +/- 13.22, P
<.001) and were more likely to be older, to be intubated, and to have longer
intensive care unit stays and higher mortality (all P < .001). Other non-African
American minorities (other minority group) had the second largest burn sizes,
most uninsured members, and lowest mortality (P < .001). On multivariate
analysis, mortality was related to African-American race, female gender, TBSA,
full-thickness burn injury, inhalation injury, uninsured status, and burn
mechanism. African-Americans were 50% more likely to have complications (P <
.001), 30% more likely to have UTIs (P = .002), and 41% more likely to get
septicemia (P < .001). Other racial minority groups had more acute respiratory
distress syndrome, pneumonias, septicemia, UTIs, length of stay, and hospital
charges when compared with Caucasian patients. Socioeconomic status was related
to mortality but inconsistently related to other outcomes. Race appears to play a
significant role in burn injury outcomes. Minority groups, especially African
Americans, have a higher risk of morbidity and mortality compared with Caucasian
patients with burns. Socioeconomic status and gender also play a significant role
in burn outcomes. Future studies should focus on delineating the reasons for this
disparity.
PMID- 28423397
TI - Trends in Use of the US Medicare Annual Wellness Visit, 2011-2014.
PMID- 28423398
TI - Treatment Restarting After Discontinuation of Adjuvant Hormone Therapy in Breast
Cancer Patients.
AB - Background: Over half of breast cancer patients discontinue their adjuvant
hormone therapy, permanently or temporarily. We aimed to identify predictors of
treatment restarting after discontinuation of adjuvant hormone therapy and to
test the hypothesis that treatment restarting is associated with better breast
cancer outcomes. Methods: We conducted a population-based cohort study by linking
data from the Stockholm-Gotland Breast Cancer Register, the Swedish Prescribed
Drug Register, and a self-reported questionnaire. We followed women diagnosed
with breast cancer (Stockholm, Sweden, 2005-2008) from their first prescription
of tamoxifen or aromatase inhibitors through January 31, 2015, and categorized
them as continuers (n = 1 607), restarters (n = 953), and nonrestarters (n = 511)
of adjuvant hormone therapy. All statistical tests were two-sided. Results:
Factors that decrease the likelihood of treatment restarting included younger age
(<50 years), higher Charlson Comorbidity Score (>=2), smaller tumor size (<20
mm), human epidermal growth factor receptor 2 negative, lymph node negative,
family history of breast cancer negative, using hormone therapy, using symptom
relieving drugs, and switching therapy between tamoxifen and aromatase
inhibitors. Restarting adjuvant hormone therapy was statistically significantly
associated with prolonged disease-free survival, with an adjusted hazard ratio of
0.61 (95% confidence interval = 0.43 to 0.87, P = .006) for restarters vs
nonrestarters. Conclusions: Our study provides-for the first time to our
knowledge-evidence that restarting adjuvant hormone therapy is associated with
better breast cancer outcomes. Clinicians now have further evidence to encourage
patients to restart their treatment after discontinuation of adjuvant hormone
therapy.
PMID- 28423399
TI - Restarting Adjuvant Hormone Therapy Improves Breast Cancer Outcomes.
PMID- 28423400
TI - RE: Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma:
Survival Analyses of 6908 Cases From the National Cancer Data Base.
PMID- 28423401
TI - Response.
PMID- 28423403
TI - RE: The Association of Dyslipidemia With Chronic Lymphocytic Leukemia: A
Population-Based Study.
PMID- 28423404
TI - Response.
PMID- 28423402
TI - Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer.
AB - Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene
highly mutated in colorectal cancers (CRC). Mutation and inactivation of this
gene is a key and early event almost uniquely observed in colorectal
tumorigenesis. Alterations in the APC gene generate truncated gene products,
leading to activation of the Wnt signaling pathway and deregulation of multiple
other cellular processes. It has been a mystery why most patients with CRC retain
a truncated APC protein, but accumulating evidence suggest that these C
terminally truncated APC proteins may have gain of function properties beyond the
well-established loss of tumor suppressive function. Here, we will review the
evidence for both the loss of function and the gain of function of APC
truncations and how together they contribute to CRC initiation and progression.
PMID- 28423406
TI - The Rise of Radiomics and Implications for Oncologic Management.
AB - Clinical medicine, particularly oncology, is progressing toward personalized
care. Whereas the terms genomics, proteomics, transcriptomics, and metabolomics
have dominated personalized medicine for the past couple decades, the concept of
radiomics was first described in 2012. This nascent concept has major
implications for personalized cancer care and involves extracting hundreds of
standardized and quantifiable imaging characteristics from diagnostic computed
tomography/magnetic resonance imaging images. The central hypothesis of radiomics
is that these libraries of quantitative individual voxel-based variables are more
sensitively associated with various clinical endpoints compared with the more
qualitative radiologic, histopathologic, and clinical data more commonly utilized
today. Because radiomics offers immense potential but has not reached a
mainstream oncologic audience, the authors discuss herein the role of radiomics
in cancer care in the future.
PMID- 28423408
TI - The Patient Knows Best: Incorporating Patient-Reported Outcomes Into Routine
Clinical Care.
PMID- 28423407
TI - Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in
Lung Cancer Patients.
AB - Background: The use of web-based monitoring for lung cancer patients is growing
in interest because of promising recent results suggesting improvement in cancer
and resource utilization outcomes. It remains an open question whether the
overall survival (OS) in these patients could be improved by using a web-mediated
follow-up rather than classical scheduled follow-up and imaging. Methods:
Advanced-stage lung cancer patients without evidence of disease progression after
or during initial treatment were randomly assigned in a multicenter phase III
trial to compare a web-mediated follow-up algorithm (experimental arm), based on
weekly self-scored patient symptoms, with routine follow-up with CT scans
scheduled every three to six months according to the disease stage (control arm).
In the experimental arm, an alert email was automatically sent to the oncologist
when self-scored symptoms matched predefined criteria. The primary outcome was
OS. Results: From June 2014 to January 2016, 133 patients were enrolled and 121
were retained in the intent-to-treat analysis; 12 deemed ineligible after random
assignment were not subsequently followed. Most of the patients (95.1%) had stage
III or IV disease. The median follow-up was nine months. The median OS was 19.0
months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental
and 12.0 months (95% CI = 8.6 to 16.4) in the control arm (one-sided P = .001)
(hazard ratio = 0.32, 95% CI = 0.15 to 0.67, one-sided P = .002). The performance
status at first detected relapse was 0 to 1 for 75.9% of the patients in the
experimental arm and for 32.5% of those in the control arm (two-sided P < .001).
Optimal treatment was initiated in 72.4% of the patients in the experimental arm
and in 32.5% of those in the control arm (two-sided P < .001). Conclusions: A web
mediated follow-up algorithm based on self-reported symptoms improved OS due to
early relapse detection and better performance status at relapse.
PMID- 28423409
TI - Different Breast Cancer Treatment Options Vary Widely in their Cost
Effectiveness.
PMID- 28423410
TI - Analysis of dislocation configurations in a [0 0 1] fcc single crystal by
electron channeling contrast imaging in the SEM.
AB - We have investigated the dislocation configurations in a [0 0 1] single crystal
of a face-centered alloy (316L stainless steel) by the electron channeling
contrast imaging (ECCI) technique in the scanning electron microscope under
controlled diffraction conditions. Specific dislocations such as piled-up
dislocations and Lomer-Cottrell dislocations were characterized by the analysis
of dislocation contrast and dislocation line trace analysis. The ECCI technique
also allows the sound estimation of the local resolved stress acting on gliding
dislocations by the analysis of the radius of curvature following a transmission
electron microscopy-based geometrical approach.
PMID- 28423411
TI - A convenient technique for live-cell observation on the surface of
polytetrafluoroethylene with a phase-contrast microscope.
AB - Phase-contrast microscopy is a convenient technique for live-cell observation on
the surface of materials with high optical transmittance. Here, we demonstrate a
novel technique to observe living cells on the surface of materials with low
optical transmittance, such as polytetrafluoroethylene (PTFE), which are widely
used in biomaterials for blood-contacting devices. The surface of a cover glass
was coated with a thin PTFE layer with sufficient transmittance, thereby enabling
the observation of living cells on the PTFE surface with a phase-contrast
microscope.
PMID- 28423412
TI - Brief presentation enhances various simultaneous contrast effects.
AB - Kaneko and Murakami (2012) demonstrated that simultaneous contrast for brightness
and color (chromatic saturation) were enhanced by flashing the stimulus very
briefly (10 ms). Here we examined whether this effect of duration generalized to
other visual features. Tilt illusion and simultaneous hue contrast were both
shown to be much stronger with a stimulus duration of 10 ms compared with 500 ms.
The similar temporal dynamics for simultaneous contrast across visual features
suggest common underlying principles.
PMID- 28423413
TI - Human perception of subresolution fineness of dense textures based on image
intensity statistics.
AB - We are surrounded by many textures with fine dense structures, such as human hair
and fabrics, whose individual elements are often finer than the spatial
resolution limit of the visual system or that of a digitized image. Here we show
that human observers have an ability to visually estimate subresolution fineness
of those textures. We carried out a psychophysical experiment to show that
observers could correctly discriminate differences in the fineness of hair-like
dense line textures even when the thinnest line element was much finer than the
resolution limit of the eye or that of the display. The physical image analysis
of the textures, along with a theoretical analysis based on the central limit
theorem, indicates that as the fineness of texture increases and the number of
texture elements per resolvable unit increases, the intensity contrast of the
texture decreases and the intensity histogram approaches a Gaussian shape.
Subsequent psychophysical experiments showed that these image features indeed
play critical roles in fineness perception; i.e., lowering the contrast made
artificial and natural textures look finer, and this effect was most evident for
textures with unimodal Gaussian-like intensity distributions. These findings
indicate that the human visual system is able to estimate subresolution texture
fineness on the basis of diagnostic image features correlated with subresolution
fineness, such as the intensity contrast and the shape of the intensity
histogram.
PMID- 28423414
TI - Discovery, Development, and Evaluation of a Horn Fly-Isolated (Diptera: Muscidae)
Beauveria bassiana (Hypocreales: Cordyciptaceae) Strain From Florida, USA.
AB - The horn fly, Haematobia irritans (L.) is an important cattle pest and
traditionally has been managed using insecticides; however, many horn fly
populations are insecticide-resistant in United States. Use of alternative
control techniques has been limited because of the challenges of managing a fly
pest on pastured cattle. After the discovery of a wild horn fly infected with
Beauveria bassiana in Florida, the fungus was cultured and evaluated for efficacy
against laboratory-reared horn flies. This fungal strain was selected for
increased virulence by passage through laboratory-reared horn fly hosts to
shorten interval from infection to fly death and subsequent conidia formation,
properties important to future use of the fungus as a biological control agent
against horn flies. After seven passages through horn fly hosts, fly mortality
was not significantly accelerated as evaluated through LT50 values, but conidia
were readily produced from these killed flies. Although further development is
needed to improve fungal efficacy, this fungal strain holds promise as a
biological control agent for inclusion in horn fly integrated pest management
programs.
PMID- 28423415
TI - The Potential Organ Involved in Cantharidin Biosynthesis in Epicauta chinensis
Laporte (Coleoptera: Meloidae).
AB - Cantharidin, a terpenoid defensive toxin mainly produced by blister beetles, is
among the most widely known insect natural products in the world. However, little
is known about the site of cantharidin biosynthesis in vivo. Our previous
research showed that 3-hydroxy-3-methylglutary-CoA reductase (HMGR) is an
essential enzyme in cantharidin biosynthesis. In this report, we further
investigated cantharidin titer and HMGR mRNA expression levels in different
tissues of male and female Epicauta chinensis, and performed a comparative
analysis of HMGR transcript levels in male Tenebrio molitor, a Tenebrionidae
beetle that cannot produce cantharidin. HMGR transcripts had a positive
correlation with cantharidin production. Furthermore, the specifically high
amounts of HMGR transcript and abundant cantharidin production in fat body of
male E. chinensis indicated the process of cantharidin synthesis may occur in the
fat body.
PMID- 28423416
TI - Beauveria bassiana (Ascomycota: Hypocreales) Introduced as an Endophyte in Corn
Plants and Its Effects on Consumption, Reproductive Capacity, and Food Preference
of Dichroplus maculipennis (Orthoptera: Acrididae: Melanoplinae).
AB - In this study, the effects of strain Beauveria bassiana (LPSC 1067) as an
endophyte in corn plants on consumption, fecundity, and food preference of
Dichroplus maculipennis were examined. We observed that the daily consumption by
grasshoppers fed with control plants was almost twice that of those that were fed
treated plants. Significant differences in fecundity of grasshoppers that were
fed with treated plants compared with those that only fed on control plants were
also observed. The number of eggs laid per female fed with control plants was
27.2, while the number of eggs laid per female that were fed during 15 d with
treated plants was 17.7. Similar results were observed when the number of
embryonated eggs was evaluated. The highest number of embryonated eggs were
recorded in those females that only fed on control plants (96%) while fewer
embryonated eggs were recorded in grasshoppers fed for 15 d with treated plants
only (25%). In relation to food preference the average consumption rate for D.
maculipennis females on control corn plants was 303.8 +/- 24.5 mg while it was
only 25 +/- 2.1 mg on plants treated with B. bassiana as an endophyte. In
summary, we observed that B. bassiana as a corn plant endophyte negatively
affected the daily consumption rate, fecundity and food preference of D.
maculipennis.
PMID- 28423417
TI - Multi-Species Mating Disruption in Cranberries (Ericales: Ericaceae): Early
Evidence Using a Flowable Emulsion.
AB - Pheromone-based mating disruption has proven to be a powerful pest management
tactic in many cropping systems. However, in the cranberry system, a viable
mating disruption program does not yet exist. There are commercially available
pheromones for several of the major pests of cranberries, including the cranberry
fruitworm, Acrobasis vaccinii Riley (Lepidoptera: Pyralidae) and blackheaded
fireworm, Rhopobota naevana (Hubner) (Lepidoptera: Tortricidae). Previous studies
have shown that mating disruption represents a promising approach for R. naevana
management although carrier and delivery technologies have remained unresolved.
The present study examined the suitability of Specialized Pheromone & Lure
Application Technology (SPLAT; ISCA Technologies, Inc., Riverside, CA), a
proprietary wax and oil blend, to serve as a pheromone carrier in the cranberry
system. In 2013 and 2014, we tested a blend of pheromones targeting A. vaccinii
and R. naevana in field-scale, replicated trials. Pheromones were loaded into
SPLAT and the resulting "SPLAT BFW CFW" formulation was deployed in commercial
cranberry marshes. We compared moth trap-catch counts within SPLAT-treated blocks
to those of conventionally managed blocks. In 2013, applications of SPLAT BFW CFW
resulted in highly successful disruption of R. naevana and promising, though
inconsistent, disruption of A. vaccinii. To improve disruption of A. vaccinii,
the pheromone load was increased in 2014, providing 92% and 74% reductions in
trap-catch for R. naevana and A. vaccinii, respectively. Importantly, larval
infestation rates in SPLAT-treated blocks were lower than those of conventionally
managed blocks. These results suggest that a multispecies mating disruption
system (SPLAT BFW CFW) may represent an effective pesticide-alternative for
serious pests of cranberries.
PMID- 28423418
TI - RNA-Seq Validation of RNAi Identifies Additional Gene Connectivity in Tribolium
castaneum (Coleoptera: Tenebrionidae).
AB - RNA interference (RNAi) is a functional genomics tool to correlate genotype and
phenotype by delivering targeted, gene-specific, and complementary dsRNA into a
host via injection, feeding, or other means in order to reduce gene expression.
In the red flour beetle, Tribolium castaneum, RNAi has been successful via
injected dsRNA at all life stages. Traditionally, successful transcript knockdown
has been quantified by qPCR on a gene-by-gene basis, where only expression of the
target gene and normalization genes are evaluated. In this study, RNA-Seq was
used to quantify transcript expression in larvae injected with dsRNA for
aspartate 1-decarboxylase (ADC), which gives a reliable phenotype of an adult
with a black cuticle instead of the wild-type red-brown. ANOVA of control, mock
injected, and ADC-dsRNA injected larvae indicated that target gene expression was
significantly (P = 0.002) reduced 4-fold, and the black phenotype was achieved in
all adults injected with ADC-dsRNA as larvae. In a pairwise analysis, significant
(P < 0.05) differential expression of other genes in ADC-injected larvae
suggested connections between gene pathways. One gene, dopamine receptor 2, was
increased in expression 227-fold (P = 0.025), presumably connected to previous
data that showed a reduction in expression of ADC results in increased levels of
dopamine. To evaluate the hypothesis that increased dopamine levels can affect
mobility, T. castaneum adults injected with ADC-dsRNA as larvae were
significantly impaired in movement tests compared to controls, similar to black
mutants in Drosophila melanogaster. The data demonstrate that RNA-Seq can reveal
gene connectivity and provide more complete data validation and analysis compared
to qPCR.
PMID- 28423419
TI - Temperature-Dependent Biological and Demographic Parameters of Coleomegilla
maculata (Coleoptera: Coccinellidae).
AB - Knowledge of the most suitable environmental conditions for an organism growth
and development is a prerequisite for developing mass rearing technology. The
temperature requirements for development and the optimal range of temperatures
for growth and reproduction of Coleomegilla maculata De Geer were studied. The
development time of individual C. maculata larvae was determined at 18, 21, 24,
27, 30, 33, and 36 degrees C. Development times were converted to development
rates and fitted to a nonlinear temperature-dependent model and to the linear day
degree model. Life and fertility table analysis was used to determine the optimal
temperature for population growth within a range of favorable temperatures
including 24, 25, 26, 27, and 28 degrees C. Nonlinear estimates of thermal
maximum (TM) for the postembryonic development of C. maculata was 35.09 +/- 10.35
degrees C. Estimation of TM based on pupal development was much lower at 27.23
+/- 1.52 degrees C. Linear and nonlinear estimates of low temperature
development threshold were 13.13 +/- and 4.77 +/- 3.03 degrees C for the whole
postembryonic development and 10.95 and 9.18 +/- 1.36 degrees C for the pupal
stage alone, respectively. The most favorable temperature for population growth
was 25 degrees C, where C. maculata showed significantly higher intrinsic rate
of increase (rm = 0.066) and significantly lower doubling time (10.57 d) than the
other favorable temperatures tested. A negative value of rm was obtained at 28
degrees C, indicating population decline occurring at this temperature making it
unfavorable for C. maculata.
PMID- 28423420
TI - Functional Response of Eretmocerus delhiensis on Trialeurodes vaporariorum by
Parasitism and Host Feeding.
AB - The parasitoid wasp, Eretmocerus delhiensis (Hymenoptera, Aphelinidae) is a
thelytokous and syn-ovigenic parasitoid. To evaluate E. delhiensis as a
biocontrol agent in greenhouse, the killing efficiency of this parasitoid by
parasitism and host-feeding, were studied. Killing efficiency can be compared by
estimation of functional response parameters. Laboratory experiments were
performed in controllable conditions to evaluate the functional response of E.
delhiensis at eight densities (2, 4, 8, 16, 32, 64, 100, and 120 third nymphal
stage) of Trialeurodes vaporariorum (Hemiptera, Aleyrodidae) on two hosts
including; tomato and prickly lettuce. The maximum likelihood estimates from
regression logistic analysis revealed type II functional response for two host
plants and the type of functional response was not affected by host plant.
Roger's model was used to fit the data. The attack rate (a) for E. delhiensis was
0.0286 and 0.0144 per hour on tomato and 0.0434 and 0.0170 per hour on prickly
lettuce for parasitism and host feeding, respectively. Furthermore, estimated
handling times (Th) were 0.4911 and 1.4453 h on tomato and 0.5713 and 1.5001 h on
prickly lettuce for parasitism and host feeding, respectively. Based on 95%
confidence interval, functional response parameters were significantly different
between the host plants solely in parasitism. Results of this study opens new
insight in the host parasitoid interactions, subsequently needs further
investigation before utilizing it for management and reduction of greenhouse
whitefly.
PMID- 28423421
TI - Efficacy of Some Wearable Devices Compared with Spray-On Insect Repellents for
the Yellow Fever Mosquito, Aedes aegypti (L.) (Diptera: Culicidae).
AB - The current Zika health crisis in the Americas has created an intense interest in
mosquito control methods and products. Mosquito vectors of Zika are of the genus
Aedes, mainly the yellow fever mosquito, Aedes aegypti. L. The use of repellents
to alter mosquito host seeking behavior is an effective method for the prevention
of mosquito-borne diseases. A large number of different spray-on repellents and
wearable repellent devices are commercially available. The efficacies of many
repellents are unknown. This study focuses on the efficacy of eleven different
repellents in reducing the number of Ae. aegypti female mosquitoes attracted to
human bait. We performed attraction-inhibition assays using a taxis cage in a
wind tunnel setting. One person was placed upwind of the taxis cage and the
mosquito movement towards or away from the person was recorded. The person was
treated with various spray-on repellents or equipped with different mosquito
repellent devices. We found that the spray-on repellents containing N,N-Diethyl
meta-toluamide and p-menthane-3,8-diol had the highest efficacy in repelling
mosquitoes compared to repellents with other ingredients. From the five wearable
devices that we tested, only the one that releases Metofluthrin significantly
reduced the numbers of attracted mosquitoes. The citronella candle had no effect.
We conclude that many of the products that we tested that were marketed as
repellents do not reduce mosquito attraction to humans.
PMID- 28423422
TI - Immunological Responses of Sesamia cretica to Ferula ovina Essential Oil.
AB - The current research was performed aiming to investigate the effects of Ferula
ovina essential oil on the fourth instar larval hemogram of Sesamia cretica. Four
main sorts of circulating hemocytes, including prohemocytes, plasmatocytes,
granulocytes (GRs), and oenocytoides, were identified in the fourth instar
larvae. Treatment of the larvae with the concentration of 1000 ppm of the
essential oil led to an enhancement of the total hemocyte and GR count followed
by a dose-dependent decrease at the concentrations of 2500 and 7000 ppm.
Plasmatocyte numbers declined in all the treatments with more significant effects
at increased doses. The greatest numbers of GRs, plasmatocytes, and total
hemocytes were found after 48 h of treatment. The highest phenol-oxidase activity
was recorded 12 h after treatment at the concentration of 2500 ppm. The highest
effect on nodule formation was exerted by the concentration of 7000 ppm 12 h
after treatment. The results of the present study clearly indicated that the
treatment of larvae by the essential oil of F. ovina decreased the numbers of
total and differential hemocyte counts although phenol-oxidase activity and the
number of nodules showed no decline in the treated larvae. These results
demonstrated that Ferula ovina essential oil has a significant effect on the
immune ability of the studied insect and can be useful and usable for future
research to practical management of this pest.
PMID- 28423423
TI - Invertebrates, Fungal Biomass, and Leaf Breakdown in Pools and Riffles of
Neotropical Streams.
AB - We evaluated fungal biomass (as ergosterol concentration) and invertebrate
colonization during leaf breakdown of Picramnia sellowii Planch. (Picramniaceae)
in pools and riffles of three low-order forested streams in southeastern Brazil.
We hypothesized that leaf breakdown will be higher in riffles due to the high
physical fragmentation and fungal activity. The experiment was carried out during
the dry season of 2012, using 108 litter bags, each containing 3 +/- 0.05 g of
air-dried leaves. After 7, 15, 30, 60, 90, and 120 d of incubation, six litter
bags (riffle = 3 and pool = 3) were removed from each stream. Leaf breakdown rate
(k) was classified as intermediate in pools and fast in riffles. We recorded
similar values of remaining leaf mass in two habitats until 60 d. However, at 90
and 120 d, this process was faster in riffles. The mean fungal biomass was
similar between habitats and showed an increase during the experiment at 90 d.
Fauna composition differed between habitats and across sampling dates, with
Chironomidae most contributing to these differences and being particularly
abundant in riffles and in the initial period of leaf breakdown (until 30 d).
Shredder abundance and biomass were not different between habitats and among
incubation durations. Leaf breakdown (remaining leaf mass) was positively
associated with fungal and shredder biomasses. However, water velocity was not
related to leaf breakdown. These findings emphasize the importance of fungal and
shredder organisms, as well as the low importance of water velocity, on mass loss
in low-order tropical streams.
PMID- 28423424
TI - Field Evaluation of Potential Pheromone Lures for Lygus lineolaris (Hemiptera:
Miridae) in the Mid-South.
AB - Plant bugs (Hemiptera: Miridae) are phytophagous pests of cultivated plants
around the world. In the mid-South region of the United States, Lygus lineolaris
(Palisot de Beauvois) is a primary pest of cotton, and causes economic damage.
Previously published research about the volatiles produced by members of the
genus Lygus, and other closely related groups, indicated that they produce blends
of hexyl butyrate, (E)-2-hexenyl butyrate, and (E)-4-oxo-2-hexenal. Varying
ratios of the three compounds were loaded into pipette tips, and screened in
combination with non-UV white sticky cards for attractiveness to field
populations of L. lineolaris in Mississippi. Field screening indicated that a
lure expressing a ratio of 4:10:7 was the most effective at collecting L.
lineolaris, and collected similar numbers of individuals to those reported in
other studies using traps baited with live virgin insects over a similar period
of time. Availability of a synthetic pheromone usable in the climate of the mid
South will enable broader scale landscape level monitoring for populations of L.
lineolaris before movement into cotton fields and resulting economic damage.
PMID- 28423425
TI - Temporal Resource Partitioning and Interspecific Correlations in a Warm,
Temperate Climate Assemblage of Dung Beetles (Coleoptera: Scarabaeidae).
AB - Guilds of dung dwelling and tunneling dung beetles coexist in local assemblages
in warm temperate regions, despite the tendency of dwellers to be inferior
competitors. A field experiment on the Black Sea coast of Turkey examined the
role of temporal resource partitioning in their coexistence. Standardized dung
pads deposited at 4 h intervals through a 24 h period in summer were collected
12, 24, or 48 h later. Adults from 10 tunneling and seven dung dwelling species
were collected. The tunnelers contributed a high proportion of both total
abundance and biomass. There was a significant effect of dung deposition time and
exposure period on mean tunneler abundance. Mean tunneler abundance was nearly
seven times higher in dung deposited at 06:00 than at 18:00. The dwellers reduced
the potential for competitive interactions with tunnelers by relatively uniform
dispersal across the six dung deposition times. The distinctly different dung use
patterns by dwellers and tunnelers demonstrated temporal resource partitioning.
Interspecific correlation coefficients were also determined because interspecific
relationships are at the core of resource partitioning. Total tunneler and
dweller abundances were not correlated. Overall, there were strong positive
correlations between tunneling species and low correlations between tunneling and
dwelling species, and between dwelling species. The five most abundant tunnelers,
from two tribes and three genera, were strongly positively correlated. There were
substantial size differences among the four most abundant tunnelers that probably
facilitate their coexistence.
PMID- 28423426
TI - The Invasive Liriomyza huidobrensis (Diptera: Agromyzidae): Understanding Its
Pest Status and Management Globally.
AB - Liriomyza huidobrensis (Blanchard) is native to South America but has expanded
its range and invaded many regions of the world, primarily on flowers and to a
lesser extent on horticultural product shipments. As a result of initial invasion
into an area, damage caused is usually significant but not necessarily sustained.
Currently, it is an economic pest in selected native and invaded regions of the
world. Adults cause damage by puncturing abaxial and adaxial leaf surfaces for
feeding and egg laying sites. Larvae mine the leaf parenchyma tissues which can
lead to leaves drying and wilting. We have recorded 365 host plant species from
49 families and more than 106 parasitoid species. In a subset of the Argentinian
data, we found that parasitoid community composition attacking L. huidobrensis
differs significantly in cultivated and uncultivated plants. No such effect was
found at the world level, probably due to differences in collection methods in
the different references. We review the existing knowledge as a means of setting
the context for new and unpublished data. The main objective is to provide an
update of widely dispersed and until now unpublished data, evaluate dispersion of
the leafminer and management strategies in different regions of the world, and
highlight the need to consider the possible effects of climate change on further
regional invasions or expansions.
PMID- 28423427
TI - Influence of Temperature and Relative Humidity on the Insecticidal Efficacy of
Metarhizium anisopliae against Larvae of Ephestia kuehniella (Lepidoptera:
Pyralidae) on Wheat.
AB - A series of laboratory bioassays were conducted for the evaluation of the
insecticidal efficacy of an isolate of Metarhizium anisopliae (Metschnikoff)
Sorokin (Ascomycota: Hypocreales) against larvae of the Mediterranean flour moth,
Ephestia kuehniella Zeller (Lepidoptera: Pyralidae), under various temperature
relative humidity (r.h.) conditions. The fungus was applied at four doses (0, 8 *
106, 8 * 108, and 8 * 1010 conidia ml-1) on wheat and insect mortality was
assessed after exposure of 1, 2, 7, and 14 d. Bioassays were conducted at three
temperatures (20, 25, and 30 degrees C) and two r.h. levels (55 and 75%).
Although complete control was not achieved in any case, the fungus provided a
considerable level of insect control. Mortality of E. kuehniella larvae on wheat
treated with M. anisopliae ranged between 41.1 and 93.3% after 14 d of exposure,
whereas the respective mortality levels in control dishes never exceeded 28.3%.
The increase of temperature resulted in most cases to higher efficacy, indicating
that temperature is an important factor for the performance of the fungus. In
contrast, in most cases r.h. did not significantly affect the efficacy of the
fungus, at least for the humidity levels tested.
PMID- 28423428
TI - Aggregation Behavior and a Putative Aggregation Pheromone in Sugar Beet Root
Maggot Flies (Diptera: Ulidiidae).
AB - Male-biased aggregations of sugar beet root maggot, Tetanops myopaeformis (Roder)
(Diptera: Ulidiidae), flies were observed on utility poles near sugar beet (Beta
vulgaris L. [Chenopodiaceae]) fields in southern Idaho; this contrasts with the
approximately equal sex ratio typically observed within fields. Peak observation
of mating pairs coincided with peak diurnal abundance of flies. Volatiles
released by individual male and female flies were sampled from 08:00 to 24:00
hours in the laboratory using solid-phase microextraction and analyzed using gas
chromatography/mass spectrometry (GC/MS). Eleven compounds were uniquely detected
from males. Three of these compounds (2-undecanol, 2-decanol, and sec-nonyl
acetate) were detected in greater quantities during 12:00-24:00 hours than during
08:00-12:00 hours. The remaining eight compounds uniquely detected from males did
not exhibit temporal trends in release. Both sexes produced 2-nonanol, but males
produced substantially higher (ca. 80-fold) concentrations of this compound than
females, again peaking after 12:00 hours. The temporal synchrony among male
aggregation behavior, peak mating rates, and release of certain volatile
compounds by males suggest that T. myopaeformis flies exhibit lekking behavior
and produce an associated pheromone. Field assays using synthetic blends of the
putative aggregation pheromone showed evidence of attraction in both females and
males.
PMID- 28423429
TI - Modeling Temperature-Dependent Development of Glyphodes pyloalis (Lepidoptera:
Pyralidae).
AB - Development of Glyphodes pyloalis Walker was studied under laboratory conditions
at constant temperatures of 12, 16, 20, 24, 28, 30, 32, and 36 degrees C. No
development occurred at 36 degrees C. Although eggs hatched at 12 oC, no larvae
were capable of developing to adult stage. At 16 oC, survival rate was low (4%)
and prepupal stage lasted 101.68 +/- 11.03 d. Larvae completed development
through six stadia at 16, 30, and 32 degrees C. Developmental time of overall
immature stages varied from 46.62 d at 20 degrees C to 22.04 d at 30 degrees C
and increased at 32 degrees C. The lower temperature thresholds of 10.30 and
11.22 degrees C, and thermal constants of 429.18 and 401.88 DD were estimated by
traditional and Ikemoto-Takai linear models, respectively. The Tmin values
estimated by Analytis, Briere-2, Lactin-2, and Sharpe-Schoolfield-Ikemoto (SSI)
for overall immature stages were 12.40, 12.92, 9.00, and 13.04 degrees C,
respectively. The fastest development temperatures (Tfast) of 31.1, 31.1, 30.8,
and 30.7 degrees C were estimated for overall immature stages based on Analytis,
Briere-2, Lactin-2, and SSI, respectively. The intrinsic optimum temperature
(Topt) estimated from the thermodynamic SSI model for total developmental time
was 24.63 degrees C, in which the maximal active state enzymes involved in
developmental process. The nonlinear models of Analytis, Lactin-2, Briere-2, and
SSI estimated the upper temperature thresholds (Tmax) at 36.66, 35.97, 38.88, and
34.05 degrees C, respectively. These findings could be used to predict the
population dynamics of G. pyloalis for an effective management.
PMID- 28423430
TI - Bioactivity of Novel Botanical Insecticide From Gnidia kaussiana (Thymeleaceae)
Against Callosobruchus maculatus (Coleoptera: Chrysomelidae) in Stored Vigna
subterranea (Fabaceae) Grains.
AB - Hexane, acetone, and methanol extracts from Gnidia kaussiana Meisn
(Thymeleaceae), each at two dosages (0.2 and 1 ml/50 g grains corresponding,
respectively to 1 and 5g/kg), and neem seed oil (NSO), used as standard
insecticide were evaluated for repellence, toxicity to Callosobruchus maculatus
(F.) (Coleoptera: Chrysomelidae) adults, F1 progeny inhibition, persistence and
as grain protectant during storage. Experiments were laid out at complete
randomized design with five replications for repellence test and four for others.
All the extracts were effective in protecting stored Bambara groundnut (Vigna
subterranea (L.) Verdcourt) from insect attack; however, their bioactivities were
inversely correlated with solvent polarity. No adult survival was recorded in
treated grains with hexane extract at 5 g/kg dosage within 2 d exposure. Also at
5 g/kg, all extracts hindered adults emergence, grain damage and weight loss
after 4 months storage. Moreover, hexane extract was more repellent and exhibited
averagely repellency. The insecticidal effectiveness of hexane extract did not
decreased provided that the exposure time of insects to the product was high (7
d). The potency of acetone and methanol extracts decreased with storage time,
although not linearly and remained significantly toxic to C. maculatus up to 60 d
of storage. Therefore, hexane and acetone extracts are good candidates for
incorporation in integrated pest management programs for control of cowpea
weevils in stored grains by poor-resourced farmers and store keepers in Cameroon
and other developing countries.
PMID- 28423431
TI - [Treatment and Secondary Prevention of Venous Thromboembolism - Change in Oral
Anticoagulation].
AB - With the recent approval of the fourth direct non vitamin K dependent oral
anticoagulant (NOAC) edoxaban the range of available NOACs for the treatment of
venous thromboembolism (VTE) has expanded. Shortly thereafter, two updated
guidelines for the prevention and treatment of VTE have been published. In these
NOACs are listed as equal anticoagulants to low-molecular weight heparin (LMWH),
or fondaparinux (FDX), and VKA for the initial or maintenance treatment of VTE.
All NOACs are approved for the maintenance therapy after VTE and two NOACs
(rivaroxaban and apixaban) for the initial treatment in addition in an increased
dose.NOACs differ in their pharmacodynamic and pharmacokinetic properties. In
patients with renal insufficiency the dose of all NOACs should be reduced
similarly to NMH/FDX. In contrast to VKAs, bridging with NOACs in case of
surgical interventions is generally dispensable. Similar to NMHs or FPX renal
function and individual bleeding risk dependent dose intermission is generally
sufficient. Conventional coagulation parameters like aPTT and INR are not
suitable for the monitoring of NOACs. Only in seldom cases, laboratory monitoring
with use of adjusted anti-Xa testing or diluted thrombin time (dabigatran) may be
helpful.
PMID- 28423432
TI - [Clinical and pathological prognostic factors for the long-term survival of
patients with pT1 renal cell carcinoma].
AB - Introduction The incidence of renal cell carcinoma (RCC) has been increasing over
the past few decades. Simultaneously, due to improved imaging, small renal masses
at stage pT1 have been diagnosed more frequently. However, it is known that even
small RCCs may recur and metastasize at a late point of time. This study aimed to
identify easy-to-assess clinical and histopathological prognostic markers for
long-term survival. Patients/Methods We performed a retrospective analysis of
patients who underwent surgical treatment of a pT1 RCC in a single centre between
1993 and 2007. The prognostic impact of clinical and histopathological parameters
was investigated regarding recurrence-free survival (RFS), cancer-specific
survival (CSS) and overall survival (OS). Univariate Kaplan-Meier analysis and
multivariate Cox regression analysis were performed using SPSS 23. Results
Overall, 571 patients were included with a median follow-up of 111 months.
Univariate analysis revealed that higher grading (p = 0.031) and stage pT1b (p <
0.001) were statistically significantly associated with worse RFS. Likewise,
stage pT1b (p = 0.001) and grading G2/3 (p = 0.019) were significantly associated
with shorter CSS. Multivariate analysis revealed that stage pT1b was the only
predictor for reduced RFS (p = 0.001) and CSS (p = 0.009). Total nephrectomy (p =
0.024), and diabetes (p < 0.001) were significantly associated with reduced OS.
Multivariate analysis revealed that multifocal tumours (p = 0.041) and diabetes
(p < 0.001) were the best predictive factors for OS. Conclusion The identified
prognostic parameters may help to provide a risk-adapted after follow-up for
patients with small renal tumours.
PMID- 28423433
TI - [Myositis Ossificans Traumatica in the Craniocervical Junction: A Case Report and
Review of Literature].
AB - Background Myosits ossificans (MO) is a rare but important differential diagnosis
for a heterotrophic bony tumor in the muscles. It is often misdiagnosed as a
malignant tumor. With a previous trauma the diagnosis is myositis ossificans
traumatic (MOT). In most cases, it is benign and predominantly seen in the big
muscles. But there can be malignant etiologies too. Case Description We report a
rare case of MO in the muscle of the craniocervical junction. This 37-year-old
woman had a riding accident years ago. Because of persisting pain and cervical
dysfunction, we did a total resection. Clinical Implications MOT is a benign
tumor that can be treated conservative in most cases. In case of persistent pain
or neurological deficits, and especially for securing diagnosis, surgical
resection is recommended.
PMID- 28423434
TI - [Radiologic Presentation in Subspine Impingement and Correlation with
Intraarticular Impingement in the Hip].
AB - Background Besides the known intraarticular femoroacetabular impingement (FAI),
recently forms of extra-articular impingement of the hip have been increasingly
recognized. Recent studies have described an extra-articular impingement between
a distal extension of the anterior inferior iliac spine (AIIS) and the femoral
neck (AIIS or subspine impingement). Evidently, an association between this
subspine impingement and an intraarticular FAI seems to exist. Little is known
about the incidence of this impingement type and the value of its radiological
diagnostics. The aim of this study was therefore to evaluate the correlation of a
subspine impingement with intraarticular femoroacetabular impingement and
radiological criteria of subspine impingement. Material and Methods In 2013
arthroscopic correction of intra-articular femoroacetabular impingement was
performed in 80 cases. This collective was evaluated for simultaneous
intraoperative findings of subspine impingement. In addition, the patients were
evaluated for radiological signs of subspine impingement in conventional X-ray. A
projection of the AIIS either below the acetabular sourcil or the anterior
acetabular rim in an AP pelvis X-ray was considered as a radiological sign of low
AIIS formation. These radiological findings were compared with the presence of
intraoperative signs for subspine impingement, which are defined as a combination
of focal capsule synovitis, labral ecchymosis close to the AIIS and a decreased
offset between the acetabular rim and the AIIS. The specificity and sensitivity
of the pre-operative radiological signs were calculated. Results A subspine
impingement was found in 17 cases (21 %, 3 female, 14 male, mean age 28 years). A
projection of the AIIS caudal to the acetabular sourcil in the AP pelvis X-ray
was represented in 15 of the 17 cases detected (sensitivity 0.90, specificity
0.88). A projection below the anterior glenoid rim was detectable in 2 cases with
symptomatic AIIS impingement (sensitivity 0.12, specificity 1). Conclusion A
relevant proportion of patients with intraarticular FAI showed intraoperative
signs for an additive extraarticular AIIS impingement. Preoperative pelvic X-rays
are helpful with a sensitivity of 90 % in detecting the presence of a distal
extension of the AIIS in FAI patients. Evaluation of the preoperative AP pelvis x
ray should include the projection of the AIIS. We recommend evaluation for
subspine impingement during routine arthroscopy.
PMID- 28423435
TI - [Pathogen Spectrum of Complex Wounds in Germany from War Zones].
AB - Background Treatment of the injured from war zones with wounds with multi
resistant pathogens is becoming more common in Germany, especially in German
Armed Forces Hospitals. In most cases, the pre-treatment of these patients has
been inadequate and they have a high load of rare pathogens. In Germany,
hospitals have to evaluate these pathogens by law. The aim of this study was to
review current German guidelines and data on the array of pathogens of complex
trauma wounds in Germany and to compare patients with wounds and multi-resistant
pathogens from war zones treated in Germany. Patients and Methods A PubMed search
was performed on all multiresistant pathogens, antibiotic resistance and
guidelines in Germany from 2005 to 2015. The databases and recommendations of the
Robert Koch Institute, the Paul Ehrlich Society and the National Reference Centre
for the Surveillance of Nosocomial Infections were analysed. The screening
results of injured patients from war zones treated in the German Armed Forces
Hospital Ulm were included. Results The array of pathogens for nosocomial
infections has not changed, but the ratios of the pathogens has altered.
Methicilin-resistant Staphylococcus aureus (MRSA) has decreased, but vancomycin
resistant enterococci have increased continuously. Enterococcus faecium (E.
faecium) now make up the largest fraction of VRE. The databases do not yet
provide data on the relatively new classification of multiresistant gramnegative
(MRGN) pathogens. MRGN pathogens play the main role in injured patients from war
zones. Conclusion In the last ten years, there have been changes in the
resistance and ratios of multi-resistant pathogens. MRSA has decreased over the
last ten years, but reserve antibiotics are increasingly needed. VRE are
increasing and even some reserve antibiotics have lost their efficacy because of
the use of modern antibiotics. There are not yet any German datasets available on
3- and 4-MRGN. These pathogens play the main role in injured patients from war
zones treated in Germany: it is crucial to perform routine screening and to take
all precautions, including isolation. Surgical wound therapy is of increasing
importance and uncritical and expensive antibiotic therapy is becoming becomes
less important.
PMID- 28423436
TI - ?
PMID- 28423437
TI - [Expert Assessment of Traumatic Disc Herniations].
AB - In numerous legal areas, expert assessments are needed to clarify the causality
of herniated discs: Was the damage caused by an accident? The literature mentions
specific requirements regarding the trauma mechanism as well as temporal
criteria, which prescribe the causality test. These are essentially high-energy
traumas with immediate functional impairments. Accident-related MRI examinations
are of paramount importance in the expert assessment process to confirm the
primary body harm. In examining the causality constituting liability, competitive
causes must be assessed. Since the legal requirements of the causality test
differ in civil and social law, legal norms need to be taken into account. We
present a test scheme that supports the assessment process through entry,
implementation and decision-making levels.
PMID- 28423438
TI - [Integration of Injured Hands].
AB - : Any injury of a hand more or less disintegrates the injured hand. The
rehabilitation of an alienated hand is prolonged. How can the alienation of the
own but injured hand and the involuntary and unconscious inhibition of its
perception and use be diagnosed, explained, avoided and designated? Medical
observations and interviews with patients and therapists on the occasion of
rehabilitation of hand injuries resulted in the development of a new concept of
biopsychosocial integrating rehabilitation and a creative hand therapy with the
objective of integrating injured and alienated hands. DIAGNOSIS: The inhibition
of the gesture of thinking has been the most revealing sign for the diagnosis of
a disintegration of an injured hand. Explanation: The involuntary inhibition to
recognize and use an injured hand causes and implicates the alienation of the
rested hand. PREVENTION: Information by hand surgeons and hand therapists.
Creative hand therapy guides the attention to complex and pleasing activities. In
complex disintegrations after hand injuries the hand as well as the person need
help. Designation: Hypotheses: Posttraumatic Proportionate Regional
Disintegration while the tissues heal. Posttraumatic Complex Regional
Disintegration, if the disintegration overruns the healing of tissues or if the
person suffers. The Complex Regional Pain Syndrome is distinguished as a rare
exception of a biopsychosocial disintegration. Posttraumatic regional
disintegration seems to be proportionate while the tissues are healing. If the
mentioned sensations of the patients and the visible signs of disintegration
persist, the disorder spreads onto the biopsychosocial unit of the person. This
disorder of hand and person may be designated as a complex disorder. The impact
of a proportionate posttraumatic disintegration as well as the formation and
exacerbation of a complex posttraumatic disintegration may be prevented by the
facilitation of the integration of an injured hand. Scientific prove is needed
for: the guiding impact of the healthy hand for physiotherapy; the impact of the
gesture of thinking to diagnosis and treatment of disintegrations; the
effectivity and the economic efficiency of a biowpsychosocial integrating
rehabilitation and creative hand therapy.
PMID- 28423439
TI - [Reliable Flaps for Congenitally Malformed Hands].
AB - Congenital hand malformations are rare, but hand function and aesthetics cannot
be improved by surgery in every affected child. However, whenever this is
possible, it is important to create an individual surgical plan for each child.
Growth has to be taken into account in the accurate planning of incisions and
local flaps. Just because it is technically possible, not every flap should be
used in the malformed child's hand. In the following article, we present a
collection of reliable flaps in the surgery of the congenitally malformed hand.
PMID- 28423440
TI - [Results After Distal Digital Replantation - Is It Worth The Effort?]
AB - There are only relative indications for distal digital replantation in zones 1
and 2 according to Tamai. In contrast to primary closure for fingertip
amputations, replantation is a complex procedure that requires skills in
supermicrosurgical techniques, as vessels with diameters between 0.3-0.8 mm are
connected. In addition the time spent in hospital and the time off from work are
longer. Distal digital replantation is thus only indicated, if the expected
functional and aesthetic benefits surmount those of primary closure. We
retrospectively analysed all fingertip amputations in zone 1 and 2 according to
Tamai between 9/2009 and 7/2014 where we attempted distal digital replantation.
The success of replantation, wound healing and functional results were evaluated
according to Yamano. We performed 11 distal digital replantations in the study
period. There were 6 total amputations, 4 subtotal amputations and 1 avulsion of
the digital pulp. Revascularisation with long-term reattachment of the amputated
tissues was possible in 8 cases (73%). In 3 cases (27%) secondary amputation
closure was necessary. The mean operating time was 3 h 56 min. 6 patients, which
had a successful replantation, were available for follow-up examinations after a
mean period of 19 months. 5 patients were satisfied with the result and would
again prefer replantation over primary amputation closure. 4 patients reported a
good function of the replanted digits and did not complain about any limitations
in their use. 2 patients complained about restricted function. All patients could
return to their previous places of employment and were free of pain. Of the 12
affected digital nerves 11 nerves had a 2-point discrimination (2-PD) of <=15 mm,
3 of them had a 2-PD between 7 and 10 mm and 4 of them of <6 mm. Soft tissue
atrophy was obvious in 3 replanted digits and nail deformities in 2 patients.
Distal digital replantation is complex and technically challenging. It leads to
high patient satisfaction with only minimal functional limitations, if
successful. Due to the good results that can be obtained by these procedures,
fingertip replantation should be attempted, if operative risks are minimal and if
requested by the patient.
PMID- 28423441
TI - [Thumb Lengthening Following Amputation at the Proximal Phalanx using a
Semicircular Distraction Ring Fixator: Results of 5 Cases].
AB - Traumatic amputation of the thumb at the proximal phalanx or the
metacarpophalangeal joint can be treated by distraction lengthening depending on
the location of the amputation, the patient's age, occupation and functional
demands. We report the results of proximal phalanx lengthening in 5 patients
using a semicircular ring-type external fixator device. This prototype was
developed at our clinic in collaboration with a specialised small company
(Rotomed AG, Allmenstrasse 4, CH-4512 Bellach, www.rotomed.ch) based on the
principles of Ilizarov's external fixator. In all patients, subjective and
objective results were satisfactory (26.2 mm distraction length and an average
Michigan Hand Outcome Score of 82.2%) without any rotational/axial deformities or
complications requiring revision surgery.
PMID- 28423442
TI - [Atypical Lipomatous Tumour of the Hand].
AB - Atypical lipomatous tumours (ALT) are rare semi-malignant adipose tissue tumours
with the potential to transform into sarcomas. They may occur throughout the
body, although the hands are very rarely involved. We present the case of a 49
year-old man with a lipomatous tumour measuring 8*4 cm at the dorsum of the right
thumb. MRI demonstrated an inhomogeneous signal after contrast medium
application. The tumour was excised in its entirety. Since histology confirmed
the diagnosis of an ALT, the thumb was irradiated. The patient remained free of
recurrence. An ALT has to be suspected if a lipomatous tumour is very large. We
recommend an MRI prior to surgery in tumours larger than 5 cm. Excision should
follow oncologic principles.
PMID- 28423443
TI - [The Extended Percutaneous Needle Fasciotomy Technique (PNF+) For Dupuytren's
Contracture].
AB - The extended percutaneous needle fasciotomy (PNF+) is a minimal invasive
technique especially suitable for treating severe Dupuytren's contractures and
recurrences. The familiar needle fasciotomy is complemented by a spontaneous
tearing of the skin and a full-thickness graft to cover the defect. Skin tears in
fingers and palm are not a complication, but an integral part of the PNF+. The
neurovascular bundles remain intact. This surgical procedure may be repeated as
often as required.
PMID- 28423444
TI - [Comment on "The Technique of Enhanced Percutaneous Needle Fasciotomy (PNF+) for
Dupuytren's Contracture"].
PMID- 28423445
TI - [Comment on the Case Report "Atypical Lipomatous Tumour of the Hand"].
PMID- 28423446
TI - [Dorsal Dislocation of the Os Trapezoideum: A Case Report].
PMID- 28423447
TI - [Type I Trichorhinophalangeal Syndrome - Rare, but Catchy].
PMID- 28423448
TI - ?
PMID- 28423449
TI - ?
PMID- 28423450
TI - ?
PMID- 28423451
TI - [Salvage Procedure after Trapeziectomy using Mini TightRope(r)].
PMID- 28423453
TI - Periodontal treatment in private dental practice: a case-based survey.
AB - BACKGROUND: This study aimed to assess the management and referral patterns of
Victorian general dental practitioners based on periodontal diagnosis. METHODS:
Following ethics approval, Victorian general dental practitioners were invited to
complete five randomized text-based periodontitis scenario questionnaires. Based
on their diagnosis, respondents were asked for their management options and asked
to specify who would perform these treatments. Respondents were also asked about
referral procedures. RESULTS: One hundred and thirty-five dentists attempted the
survey. Most were in group practice and based in Melbourne. Of the total
respondents, 22.5% worked in a practice employing a hygienist. The management of
periodontal disease was appropriate, and treatment options increased with
severity. As severity increased, patients were more likely to be referred to a
periodontist. Periodontal services referred by general dentists to dental
hygienists increased with the number of days the hygienists worked within a
practice. Over- and underdiagnosis did not markedly affect management. The
recommendation of antibiotics, mouthwashes and periodontal surgery varied
depending on year and school of graduation. CONCLUSIONS: The general dentists
that completed the survey are managing periodontal conditions appropriately and
according to current guidelines.
PMID- 28423454
TI - UK NEQAS survey of allergen component testing across the United Kingdom and other
European countries.
AB - The clinical utility of molecular diagnostic approaches in allergy investigation
is being recognized increasingly to play a significant role in the management of
allergic patients. Determining the sensitization pattern, which is best achieved
through the use of component resolved diagnostics (CRD), allows effective risk
stratification, appropriate treatment and patient selection for immunotherapy. In
order to assess the diagnostic service provisions for in-vitro allergy testing
across Europe, a survey was carried out via the total immunoglobulin (Ig)E and
specific IgE external quality assurance schemes run by UK National External
Quality Assessment Service (NEQAS) Immunology, Immunochemistry and Allergy. This
survey assessed allergy testing, and in particular allergen components offered by
the laboratories, and found a wide variability in service provision, particularly
between the United Kingdom and other European Union (EU) countries. Furthermore,
there was lack of standardization for acquisition of clinical information to aid
allergen (and component) selection, gating strategy, testing algorithms and
clinical interpretation. Interestingly, a significant proportion of laboratories
(the majority from EU) stated that they 'used' the results for peanut components
for risk stratification. However, the vast majority of participants were unaware
of guidelines relating to the use of allergen component testing, and agreed that
further education would assist in reaching a common platform. Hence, this survey
has highlighted that although CRD has been adopted into routine diagnostics
across Europe, it is potentially compromised by lack of standardized protocols
and guidance sources. Consequently, there is a need for local or national
standards and education through External Quality Assurance services on the
performance and application of CRD into allergy investigation.
PMID- 28423455
TI - Simulation and curriculum design: a global survey in dental education.
AB - BACKGROUND: Curriculum reforms are being driven by globalization and
international standardization. Although new information technologies such as
dental haptic virtual reality (VR) simulation systems have provided potential new
possibilities for clinical learning in dental curricula, infusion into curricula
requires careful planning. METHODS: This study aimed to identify current patterns
in the role and integration of simulation in dental degree curricula
internationally. An original internet survey was distributed by invitation to
clinical curriculum leaders in dental schools in Asia, Europe, North America, and
Oceania (Australia and New Zealand). RESULTS: The results (N = 62) showed Asia,
Europe and Oceania tended towards integrated curriculum designs with North
America having a higher proportion of traditional curricula. North America had
limited implementation of haptic VR simulation technology but reported the
highest number of scheduled simulation hours. Australia and New Zealand were the
most likely regions to incorporate haptic VR simulation technology. CONCLUSIONS:
This survey indicated considerable variation in curriculum structure with
regionally-specific preferences being evident in terms of curriculum structure,
teaching philosophies and motivation for incorporation of VR haptic simulation
into curricula. This study illustrates the need for an improved evidence base on
dental simulations to inform curriculum designs and psychomotor skill learning in
dentistry.
PMID- 28423456
TI - Progesterone resistance in endometriosis: origins, consequences and
interventions.
AB - Endometriosis is a common cause of pelvic pain and affects up to 10% of women of
reproductive age. Aberrant progesterone signaling in the endometrium plays a
significant role in impaired decidualization and establishment of ectopic
endometrial implants. Eutopic endometrial cells from women with endometriosis
fail to downregulate genes needed for decidualization, such as those involved in
cell cycle regulation, leading to unbridled proliferation. Several causes of
progesterone resistance in the endometrium have been postulated, including
congenital "preconditioning", whereby the in utero environment renders infants
susceptible to neonatal uterine bleeding and endometriosis. Progesterone action
is crucial to decreasing inflammation in the endometrium, and deviant
progesterone signaling results in a proinflammatory phenotype. Conversely,
chronic inflammation can induce a progesterone-resistant state. Repetitive
retrograde endometrial shedding begets chronic peritoneal inflammation, which
further exacerbates progesterone resistance. Genetic causes of progesterone
resistance include progesterone receptor gene polymorphisms, altered microRNA
expression, and epigenetic modifications to progesterone receptors and their
targets. Environmental toxins such as dioxin play a possible role in the genesis
of endometriosis by permitting an inflammatory milieu. A consequence of impaired
progesterone action is that hormonal therapy is rendered ineffective for a subset
of women with endometriosis. Synthetic progestins, such as dienogest, may
overcome this phenomenon by increasing progesterone receptor expression and
decreasing proinflammatory cytokines. Other modalities include high dose depot
formulations of progestins, medicated intrauterine devices and the likely advent
of oral GnRH antagonists. Unearthing root causes of progesterone inaction in
endometriosis will aid in the development of novel therapeutics geared toward
prevention and treatment.
PMID- 28423457
TI - Use of Online Health Information by Geriatric and Adult Emergency Department
Patients: Access, Understanding, and Trust.
AB - OBJECTIVE: The objective was to characterize geriatric patients' use of online
health information (OHI) relative to younger adults and assess their comfort ith
OHI compared to health information (HI) from their physician. METHODS: This was a
prospective cross-sectional survey study of adult emergency department (ED)
patients. The survey assessed patients' self-reported use of OHI in the past year
and immediately prior to ED visit and analyzed differences across four age
groups: 18-39, 40-64, 65-74, and 75+. Patients' ability to access, understand,
and trust OHI was assessed using a 7-point Likert scale and compared to parallel
questions regarding HI obtained from their doctor. Patient use of OHI was
compared across age groups. Comfort with OHI and HI obtained from a doctor was
compared across age groups using the Kruskal-Wallis test. Comparisons between
sources of HI were made within age groups using the Wilcoxon signed-rank test.
RESULTS: Of 889 patients who were approached for study inclusion, 723 patients
(81.3%) completed the survey. The majority of patients had used OHI in the past
year in all age groups, but older patients were less likely to have used OHI: age
18-39, 90.3%; 40-64, 85.3%; 65-74, 76.4%; and 75+, 50.7% (p < 0.001). The
youngest patients were most likely to have used OHI prior to coming to the ED,
47.1%, 28.3%, 17.1%, and 8.0% (p < 0.001). Older patients were more likely to
have an established doctor-18-39, 79.4%; 40-64, 91.1%; 65-74, 97.5%; and 75+
97.4% (p < 0.001)-and were more likely to have contacted their doctor prior to
their ED visit: 36.7, 40.2, 46.7, and 53.5% (p = 0.02). The oldest patients were
most likely to find HI more accessible from their doctor than the Internet, while
the youngest patients found HI more accessible on the Internet than from their
doctor. Regardless of age, patients noted that information from their physician
was both easier to understand and more trustworthy than information found on the
Internet. CONCLUSION: Although many older patients used OHI, they were less
likely than younger adults to use the Internet immediately prior to an ED visit.
Despite often using OHI, patients of all age groups found healthcare information
from their doctor easier to understand and more trustworthy than information from
the Internet. As health systems work to efficiently provide information to
patients, addressing these perceived deficiencies may be necessary to build
effective OHI programs.
PMID- 28423458
TI - Dissecting virulence function from recognition: cell death suppression in
Nicotiana benthamiana by XopQ/HopQ1-family effectors relies on EDS1-dependent
immunity.
AB - Many Gram-negative plant pathogenic bacteria express effector proteins of the
XopQ/HopQ1 family which are translocated into plant cells via the type III
secretion system during infection. In Nicotiana benthamiana, recognition of
XopQ/HopQ1 proteins induces an effector-triggered immunity (ETI) reaction which
is not associated with strong cell death but renders plants immune against
Pseudomonas syringae and Xanthomonas campestris pv. vesicatoria strains.
Additionally, XopQ suppresses cell death in N. benthamiana when transiently co
expressed with cell death inducers. Here, we show that representative XopQ/HopQ1
proteins are recognized similarly, likely by a single resistance protein of the
TIR-NB-LRR class. Extensive analysis of XopQ derivatives indicates the
recognition of structural features. We performed Agrobacterium-mediated protein
expression experiments in wild-type and EDS1-deficient (eds1) N. benthamiana
leaves, not recognizing XopQ/HopQ1. XopQ recognition limits multiplication of
Agrobacterium and attenuates levels of transiently expressed proteins.
Remarkably, XopQ fails to suppress cell death reactions induced by different
effectors in eds1 plants. We conclude that XopQ-mediated cell death suppression
in N. benthamiana is due to the attenuation of Agrobacterium-mediated protein
expression rather than the cause of the genuine XopQ virulence activity. Thus,
our study expands our understanding of XopQ recognition and function, and also
challenges the commonly used co-expression assays for elucidation of in planta
effector activities, at least under conditions of ETI induction.
PMID- 28423459
TI - Breaks in MODIS time series portend vegetation change: verification using long
term data in an arid grassland ecosystem.
AB - Frequency and severity of extreme climatic events are forecast to increase in the
21st century. Predicting how managed ecosystems may respond to climatic extremes
is intensified by uncertainty associated with knowing when, where, and how long
effects of extreme events will be manifest in an ecosystem. In water-limited
ecosystems with high inter-annual variability in rainfall, it is important to be
able to distinguish responses that result from seasonal fluctuations in rainfall
from long-term directional increases or decreases in precipitation. A tool that
successfully distinguishes seasonal from directional biomass responses would
allow land managers to make informed decisions about prioritizing mitigation
strategies, allocating human resource monitoring efforts, and mobilizing
resources to withstand extreme climatic events. We leveraged long-term
observations (2000-2013) of quadrat-level plant biomass at multiple locations
across a semiarid landscape in southern New Mexico to verify the use of
Normalized Difference Vegetation Index (NDVI) time series derived from 250-m
Moderate Resolution Imaging Spectroradiometer (MODIS) data as a proxy for changes
in aboveground productivity. This period encompassed years of sustained drought
(2000-2003) and record-breaking high rainfall (2006 and 2008) followed by
subsequent drought years (2011 through 2013) that resulted in a restructuring of
plant community composition in some locations. Our objective was to decompose
vegetation patterns derived from MODIS NDVI over this period into contributions
from (1) the long-term trend, (2) seasonal cycle, and (3) unexplained variance
using the Breaks for Additive Season and Trend (BFAST) model. BFAST breakpoints
in NDVI trend and seasonal components were verified with field-estimated biomass
at 15 sites that differed in species richness, vegetation cover, and soil
properties. We found that 34 of 45 breaks in NDVI trend reflected large changes
in mean biomass and 16 of 19 seasonal breaks accompanied changes in the
contribution to biomass by perennial and/or annual grasses. The BFAST method
using satellite imagery proved useful for detecting previously reported ground
based changes in vegetation in this arid ecosystem. We demonstrate that time
series analysis of NDVI data holds potential for monitoring landscape condition
in arid ecosystems at the large spatial scales needed to differentiate responses
to a changing climate from responses to seasonal variability in rainfall.
PMID- 28423461
TI - Attributes of the complete dental record: a Delphi approach to standards.
AB - BACKGROUND: Adherence to the Dental Board of Australia Guidelines on dental
records is not universal and remediation of deficient practise requires clarity
in the practical application of standards. The aim of this research is to clarify
practical requirements of dental record keeping in New South Wales. METHODS:
Seventeen experts were invited to participate in an electronically administered
series of Delphi questionnaires. Concepts were refined until consensus was
reached. RESULTS: Two rounds were required to achieve a satisfactory level of
consensus (>80%). A high level of consensus was obtained across the two rounds,
with 72% and 86% agreement on propositions in the first and second rounds,
respectively. Consensus criteria were established in 14 domains to establish
attributes of the complete dental record (ACDR). CONCLUSIONS: The ACDR may
supplement existing national guidelines and are likely to be useful in a
remediation context in which clear, unambiguous expectations for conduct are
paramount.
PMID- 28423460
TI - Individual and Neighborhood Characteristics of Children Seeking Emergency
Department Care for Firearm Injuries Within the PECARN Network.
AB - OBJECTIVE: The objective was to describe the characteristics of children seeking
emergency care for firearm injuries within the PECARN network and assess the
influence of both individual and neighborhood factors on firearm-related injury
risk. METHODS: This was a retrospective, multicenter cross-sectional analysis of
children (<19 years old) presenting to 16 pediatric EDs (2004-2008). ICD-9-CM E
codes were used to identify and categorize firearm injuries by mechanism/intent.
Neighborhood variables were derived from home address data. Multivariable
analysis examined the influence of individual and neighborhood factors on firearm
related injuries compared to nonfirearm ED visits. Injury recidivism was
assessed. RESULTS: A total of 1,758 pediatric ED visits for firearm-related
injuries were analyzed. Assault (51.4%, n = 904) and unintentional injury (33.2%,
n = 584) were the most common injury mechanisms. Among children with firearm
injuries, 68.3% were older adolescents (15-19 years old), 82.3% were male, 68.2%
were African American, and 76.3% received public insurance/were uninsured.
Extremity injuries were most common (75.9%), with 20% sustaining injuries to
multiple body regions, 48.1% requiring admission and 1% ED mortality.
Multivariable analysis identified firearm injury risk factors, including
adolescent age (p < 0.001), male sex (p < 0.001), non-Caucasian race/ethnicity (p
< 0.001), public payer/uninsured status (p < 0.001), and higher levels of
neighborhood disadvantage (p < 0.001). Among children with firearm injuries, 12
month ED recidivism for any reason was 22.4%, with < 1% returning for another
firearm injury. CONCLUSION: Among children receiving ED treatment within the
PECARN network, there are distinct demographic and neighborhood factors
associated with firearm injuries. Among younger children (<10 years old),
unintentional injuries predominate, while assault-type injuries were most common
among older adolescents. Overall, among this PECARN patient population, male
adolescents living in neighborhoods characterized by high levels of concentrated
disadvantage had an elevated risk for firearm injury. Public health efforts
should focus on developing and implementing initiatives addressing risk factors
at both the individual and the community level, including ED-based interventions
to reduce the risk for firearm injuries among high-risk pediatric populations.
PMID- 28423462
TI - Geochemical signatures of benthic foraminiferal shells from a heat-polluted
shallow marine environment provide field evidence for growth and calcification
under extreme warmth.
AB - Shallow marine calcifiers play an important role as marine ecosystem engineers
and in the global carbon cycle. Understanding their response to warming is
essential to evaluate the fate of marine ecosystems under global change
scenarios. A rare opportunity to test the effect of warming acting on natural
ecosystems is by investigation of heat-polluted areas. Here, we study growth and
calcification in benthic foraminifera that inhabit a thermally polluted coastal
area in Israel, where they are exposed to elevated temperatures reaching up to
~42 degrees C in summer. Live specimens of two known heat-tolerant species
Lachlanella sp. 1 and Pararotalia calcariformata were collected over a period of
1 year from two stations, representing thermally polluted and undisturbed
(control) shallow hard bottom habitats. Single-chamber element ratios of these
specimens were obtained using laser ablation, and the Mg/Ca of the most recently
grown final chambers were used to calculate their calcification temperatures. Our
results provide the first direct field evidence that these foraminifera species
not only persist at extreme warm temperatures but continue to calcify and grow.
Species-specific Mg/Ca thermometry indicates that P. calcariformata precipitate
their shells at temperatures as high as 40 degrees C and Lachlanella sp. 1 at
least up to 36 degrees C, but both species show a threshold for calcification at
cold temperatures: calcification in P. calcariformata only occurred above 22
degrees C and in Lachlanella sp. 1 above 15 degrees C. Our observations from the
heat-polluted area indicate that under future warming scenarios, calcification in
heat-tolerant foraminifera species will not be inhibited during summer, but
instead the temperature window for their calcification will be expanded
throughout much of the year. The observed inhibition of calcification at low
temperatures indicates that the role of heat-tolerant foraminifera in carbonate
production will most likely increase in future decades.
PMID- 28423463
TI - Temperature regulation of marine heterotrophic prokaryotes increases
latitudinally as a breach between bottom-up and top-down controls.
AB - Planktonic heterotrophic prokaryotes make up the largest living biomass and
process most organic matter in the ocean. Determining when and where the biomass
and activity of heterotrophic prokaryotes are controlled by resource availability
(bottom-up), predation and viral lysis (top-down) or temperature will help in
future carbon cycling predictions. We conducted an extensive survey across
subtropical and tropical waters of the Atlantic, Indian and Pacific Oceans during
the Malaspina 2010 Global Circumnavigation Expedition and assessed indices for
these three types of controls at 109 stations (mostly from the surface to 4,000 m
depth). Temperature control was approached by the apparent activation energy in
eV (ranging from 0.46 to 3.41), bottom-up control by the slope of the log-log
relationship between biomass and production rate (ranging from -0.12 to 1.09) and
top-down control by an index that considers the relative abundances of
heterotrophic nanoflagellates and viruses (ranging from 0.82 to 4.83). We
conclude that temperature becomes dominant (i.e. activation energy >1.5 eV)
within a narrow window of intermediate values of bottom-up (0.3-0.6) and top-down
0.8-1.2) controls. A pervasive latitudinal pattern of decreasing temperature
regulation towards the Equator, regardless of the oceanic basin, suggests that
the impact of global warming on marine microbes and their biogeochemical function
will be more intense at higher latitudes. Our analysis predicts that 1 degrees C
ocean warming will result in increased biomass of heterotrophic prokaryoplankton
only in waters with <26 degrees C of mean annual surface temperature.
PMID- 28423465
TI - Febrile status epilepticus due to respiratory syncytial virus infection.
AB - BACKGROUND: Febrile status epilepticus can have neurological sequelae. The type
of sequelae, however, depend on the etiology, including infection due to viral
agents such as the influenza virus. Respiratory syncytial virus (RSV) infection
in childhood may also contribute to this. The aim of this study was therefore to
characterize febrile status epilepticus associated with RSV infection, and to
determine whether this type of infection is a risk factor for neurological
sequelae in febrile status epilepticus. METHODS: We reviewed the medical records
of children aged <=3 years with febrile status epilepticus who were admitted to a
tertiary hospital between January 2007 and December 2011. The differences between
the RSV-positive and RSV-negative groups were evaluated according to the
demographic and clinical data. RESULTS: A total of 99 patients with febrile
status epilepticus who had been tested for RSV infection were identified. Three
patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n
= 80) presented with bronchiolitis. The incidence of intubation and anti-seizure
drug treatment in the RSV-positive group was significantly higher than in the
negative group. While all of the patients in the RSV-negative group recovered
completely, six patients in the RSV-positive group developed encephalopathy and
profound neurological sequelae. In five of the six patients, diffusion-weighted
magnetic resonance imaging showed subcortical white matter lesions. CONCLUSIONS:
RSV infection in the absence of bronchiolitis can initially present as febrile
status epilepticus and subsequently develop into acute encephalopathy with
profound neurological sequelae.
PMID- 28423464
TI - High clinical suspicion of donor-derived disease leads to timely recognition and
early intervention to treat solid organ transplant-transmitted lymphocytic
choriomeningitis virus.
AB - Despite careful donor screening, unexpected donor-derived infections continue to
occur in organ transplant recipients (OTRs). Lymphocytic choriomeningitis virus
(LCMV) is one such transplant-transmitted infection that in previous reports has
resulted in a high mortality among the affected OTRs. We report a LCMV case
cluster that occurred 3 weeks post-transplant in three OTRs who received
allografts from a common organ donor in March 2013. Following confirmation of
LCMV infection at Centers for Disease Control and Prevention, immunosuppression
was promptly reduced and ribavirin and/or intravenous immunoglobulin therapy were
initiated in OTRs. The liver recipient died, but right kidney recipients survived
without significant sequelae and left kidney recipient survived acute LCMV
infection with residual mental status deficit. Our series highlights how early
recognition led to prompt therapeutic intervention, which may have contributed to
more favorable outcome in the kidney transplant recipients.
PMID- 28423466
TI - Zonulin transgenic mice show altered gut permeability and increased
morbidity/mortality in the DSS colitis model.
AB - Increased small intestinal permeability (IP) has been proposed to be an integral
element, along with genetic makeup and environmental triggers, in the pathogenies
of chronic inflammatory diseases (CIDs). We identified zonulin as a master
regular of intercellular tight junctions linked to the development of several
CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of
CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate
(DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to
C57Bl/6 (wild-type (WT)) mice. IP was measured in vivo and ex vivo, and weight,
histology, and survival were monitored. To mechanistically link zonulin-dependent
impairment of small intestinal barrier function with clinical outcome, Ztm were
treated with the zonulin inhibitor AT1001 added to drinking water in addition to
DSS. We observed increased morbidity (more pronounced weight loss and colitis)
and mortality (40-70% compared with 0% in WT) at 11 days post-DSS treatment in
Ztm compared with WT mice. Both in vivo and ex vivo measurements showed an
increased IP at baseline in Ztm compared to WT mice, which was exacerbated by DSS
treatment and was associated with upregulation of zonulin gene expression
(fourfold in the duodenum, sixfold in the jejunum). Treatment with AT1001
prevented the DSS-induced increased IP both in vivo and ex vivo without changing
zonulin gene expression and completely reverted morbidity and mortality in Ztm.
Our data show that zonulin-dependent small intestinal barrier impairment is an
early step leading to the break of tolerance with subsequent development of CIDs.
PMID- 28423467
TI - Early life antibiotic use and the risk of asthma and asthma exacerbations in
children.
AB - BACKGROUND: The use of antibiotic therapy early in life might influence the risk
of developing asthma. Studies assessing the influence of early life antibiotic
use on the risk of asthma exacerbations are limited, and the results are
inconsistent. Therefore, the aim of this study was to assess the association
between use of antibiotic during the first 3 years of life and the risk of
developing childhood asthma and the occurrence of asthma exacerbations. METHODS:
Data from four large childhood cohorts were used; two population-based cohorts to
study the risk of developing asthma: Generation R (n=7393, The Netherlands) and
SEATON (n=891, Scotland, UK), and two asthma cohorts to assess the risk of asthma
exacerbations: PACMAN (n=668, The Netherlands) and BREATHE (n=806, Scotland, UK).
Odds ratios (ORs) were derived from logistic regression analysis within each
database followed by pooling the results using a fixed- or random-effect model.
RESULTS: Antibiotic use in early life was associated with an increased risk of
asthma in a meta-analysis of the Generation R and SEATON data (OR: 2.18, 95% CI:
1.04-4.60; I2 : 76.3%). There was no association between antibiotic use in early
life and risk of asthma exacerbations later in life in a meta-analysis of the
PACMAN and BREATHE data (OR: 0.93, 95% CI: 0.65-1.32; I2 : 0.0%). CONCLUSION:
Children treated with antibiotic in the first 3 years of life are more likely to
develop asthma, but there is no evidence that the exposure to antibiotic is
associated with increased risk of asthma exacerbations.
PMID- 28423468
TI - Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.
AB - Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other
organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found
in plant foods, have shown protective effects against Cd-induced damage. The
cytoprotective effects of flavonoids against Cd-induced diseases are mainly
attributable to three mechanisms. First, flavonoids clear reactive oxygen
species, thereby reducing lipid peroxide production and improving the activity of
antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the
accumulation of Cd and altering the levels of other essential metal ions in vivo.
Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition,
flavonoids were found to inhibit inflammation and fibrosis and improve
glycometabolism and the secretion of reproductive hormones. We introduce the
daily dosage and absorption rate of flavonoids and then focus on their bioactive
effects against Cd-induced toxicity and reveal the underlying metabolic pathway,
which provides a basis for further study of the nutritional prevention of Cd
induced injury. In particular, a better understanding is needed of the structure
activity relationship of flavonoids against Cd toxicity, which has not yet been
reported.
PMID- 28423469
TI - Cytomegalovirus peritonitis after kidney transplantation diagnosed through
histopathological examination.
AB - Among organ transplant recipients, cytomegalovirus (CMV) commonly results in
various types of infection such as pneumonitis, hepatitis, and enterocolitis.
However, CMV peritonitis is very rare and difficult to diagnose owing to lack of
visible clinical signs. We present a case of a 35-year-old female kidney
recipient who developed abdominal pain and urinary retention caused by CMV
peritonitis. To our knowledge, this is the first case report of CMV peritonitis
after organ transplantation to be diagnosed through histopathological
examination.
PMID- 28423470
TI - Quantification of near-attomole gibberellins in floral organs dissected from a
single Arabidopsis thaliana flower.
AB - There remains a methodological bottleneck in the quantification of ultra-trace
plant hormones in very tiny plant organs at fresh weights below a milligram. The
challenge becomes even more serious in the determination of endogenous
gibberellins (GAs), which are a class of compounds that are difficult to separate
and detect. Herein, a quantification method using ultra-high-performance liquid
chromatography-tandem mass spectrometry was developed, combined with a
derivatization technique in which GAs react with N-(3-dimethylaminopropyl)-N'
ethylcarbodiimide in ethanol. The method was validated as capable of determining
GAs in floral organs (about 80-250 MUg) - pistil, stamens, petals, sepals and
receptacle - which were dissected from only one flower of Arabidopsis thaliana.
Substantially different abundance patterns of GAs were measured from the floral
organs at floral stages 13, 14 and 15 along the non-13-hydroxylation pathway and
the early 13-hydroxylation pathway in plants. This allows sub-flower-level
insights into how GAs affect floral development. The method exhibited excellent
limit of detection and limit of quantification down to 5.41 and 18.0 attomole,
respectively, and offered a fairly wide linear range from 0.01 to 25 femtomole
with linear coefficients above 0.9961. The precision of the method was evaluated
with relative standard deviations below 10.6% for intra-day and 11.4% for inter
day assays, and recoveries ranged from 64.0% to 107%.
PMID- 28423471
TI - Career Cartography: From Stories to Science and Scholarship.
AB - PURPOSE: To present four case scenarios reflecting the process of research career
development using career cartography. ORGANIZING CONSTRUCTS: Career cartography
is a novel approach that enables nurses, from all clinical and academic settings,
to actively engage in a process that maximizes their clinical, teaching,
research, and policy contributions that can improve patient outcomes and the
health of the public. METHODS: Four early-career nurse researchers applied the
career cartography framework to describe their iterative process of research
career development. They report the development process of each of the components
of career cartography, including destination statement, career map, and policy
statement. CONCLUSIONS: Despite diverse research interests and career mapping
approaches, common experiences emerged from the four nurse researchers. Common
lessons learned throughout the career cartography process include: (a) have a
supportive mentorship team, (b) start early and reflect regularly, (c) be brief
and to the point, (d) keep it simple and avoid jargon, (e) be open to change, (f)
make time, and (g) focus on the overall career destination. CLINICAL RELEVANCE:
These four case scenarios support the need for nurse researchers to develop their
individual career cartography. Regardless of their background, career cartography
can help nurse researchers articulate their meaningful contributions to science,
policy, and health of the public.
PMID- 28423472
TI - Simultaneous structural identification of diacylglyceryl-N-trimethylhomoserine
(DGTS) and diacylglycerylhydroxymethyl-N,N,N-trimethyl-beta-alanine (DGTA) in
microalgae using dual Li+ /H+ adduct ion mode by ultra-performance liquid
chromatography/quadrupole time-of-flight mass spectrometry.
PMID- 28423473
TI - Prediction of cashew nut allergy in sensitized children.
PMID- 28423474
TI - Nasal obstructive disorders impair health-related quality of life in adolescents
with persistent allergic rhinitis: A real-life study.
AB - BACKGROUND: We previously reported a higher prevalence of nasal obstructive
disorders (NOD) in pediatric patients with persistent allergic rhinitis (PER) not
responding to medical treatment. The aim of this study was to determine the
impact of NOD on quality of life (QoL) in this population. METHODS: Real-life
prospective study including 142 patients (41 children, 6-11 years old and 101
adolescents, 12-17 years old) with moderate and severe PER. After 2 months of
medical treatment (intranasal steroids and antihistamines), patients were asked
whether their symptoms had improved (yes/no) and classified accordingly in R,
responders and NR, non-responders. Nasal symptoms (visual analog scale, VAS), NOD
(nasal endoscopy), and QoL (PRQLQ, AdolQRLQ) were also assessed. RESULTS: Sixty
nine adolescents and 24 children were included in the NR group. NR presented
worse QoL overall scores in adolescents (3.16+/-1.1 vs 1.63+/-0.99; P=.00001) and
children (2.19+/-0.82 vs 1.51+/-0.77, P=.02). Medical treatment failure was
associated with worse outcomes in QoL (adolescents OR: 1.6, P<.0001; children OR:
1.04, P=.036). Female adolescents presented worse QoL scores than males (3.19 vs
2.36, P=.001). The presence of obstructive septal deviation (OR: 1.02, P=.005),
obstructive turbinate hyperplasia (OR: 1.03, P=.0006), and coexistence of both
(OR=2.06, P=.001) was associated with worse QoL in adolescents. A strong and
highly significant correlation was found between nasal symptoms VAS and QoL.
CONCLUSION: The presence of NOD, particularly in adolescents, is associated with
poor QoL outcomes. Assessment of NOD in pediatric PER should be considered an
essential approach to determine the response to treatment and its impact on
patient's QoL.
PMID- 28423475
TI - Primary lymphocytic hypophysitis: Clinical characteristics and treatment of 50
cases in a single centre in China over 18 years.
AB - OBJECTIVE: Primary lymphocytic hypophysitis (LYH) is rare, and it is often
evaluated in a small case series. This study aimed to describe the diagnosis and
treatment of primary LYH in a larger cohort. DESIGN: A retrospective study of the
diagnosis and treatment of primary LYH was conducted at Peking Union Medical
College Hospital from 1999 to 2016. PATIENTS: Fifty patients (28 histologically
diagnosed and 22 clinically-diagnosed) were eligible for inclusion. MEASUREMENTS:
Clinical, endocrine, pathological and imaging findings; therapies and outcomes
were assessed. Ordinal logistic regression analysis was used to evaluate the
association between the clinical parameters and outcomes (eg, improvements in
pituitary function, regression of lesion size on MRI and disease recurrence).
RESULTS: Central diabetes insipidus (CDI) (72.0%) was the most common endocrine
dysfunction. Hypogonadotropic hypogonadism was the most frequently observed
(60.0%) manifestation of anterior pituitary dysfunction; adrenal insufficiency
was the third most common (26.0%) manifestation; and IGF-1 axis defects were the
least frequent (22.0%). Thickening of the pituitary stalk was the most frequent
(96.0%) imaging finding, and 78.0% of the patients exhibited both intrasellar and
suprasellar expansion. Pharmacological dose of glucocorticoids was identified to
be significantly associated with increased odds of anterior pituitary function
improvement. No observed covariates were significantly associated with
improvement of CDI and recurrence. CONCLUSION: The sequence of anterior pituitary
deficiencies in Chinese primary LYH patients was atypical (LH/FSH>TSH>ACTH>IGF-1
axis deficiency). A pharmacological dose of glucocorticoids was significantly
associated with the improved anterior pituitary insufficiency.
PMID- 28423476
TI - Dietary Patterns and Alcohol Consumption During Pregnancy: Secondary Analysis of
Avon Longitudinal Study of Parents and Children.
AB - BACKGROUND: Large general population surveys show that heavy regular and episodic
alcohol consumption are associated with lower intakes of fruits and vegetables,
and higher intakes of processed and fried meat. This is of particular concern
regarding pregnant women, as both alcohol intake and inadequate maternal
nutrition are independently associated with adverse fetal outcomes. The current
study aimed to determine associations between maternal dietary patterns and
alcohol consumption during pregnancy. METHODS: Women were participating in the
Avon Longitudinal Study of Parents and Children, and provided details of alcohol
consumption at 18 weeks' gestation and diet at 32 weeks' gestation (n = 9,839).
Dietary patterns were derived from the food frequency questionnaire data using
principal components analysis. Associations between alcohol consumption and
dietary patterns were determined using multiple linear regression, adjusted for
various sociodemographic and lifestyle factors. RESULTS: After adjustment,
drinking >=1 unit/d during the first trimester (beta = 0.23 [95% CI: 0.08, 0.38];
p = 0.002) and binge drinking (>=4 units in 1 day) during the first half of
pregnancy (beta = 0.14 [95% CI: 0.07, 0.21]; p < 0.0001) were associated with
greater adherence to the "Processed" dietary pattern (high intakes of processed
meat and low intakes of fruit and vegetables). Light-to-moderate alcohol
consumption (<=1 drink/d) during the first trimester was associated with greater
adherence to the "Health conscious" dietary pattern (high intakes of fruit,
vegetables, whole grains, and fish) (beta = 0.09 [95% CI: 0.04, 0.14]; p <
0.0001). CONCLUSIONS: Two important components of health behavior during
pregnancy appear to be related: greater consumption of processed foods associated
with heavier alcohol consumption, and healthier dietary choices associated with
light-to-moderate alcohol intake. Potential synergistic effects of these
behaviors may have implications for maternal and fetal health and warrant further
investigation. A more holistic approach to addressing health behaviors in women
of reproductive age is required.
PMID- 28423477
TI - Something has shifted: Nursing students' global perspective following
international clinical placements.
AB - AIMS: To examine understandings of global health issues among nursing students
following participation in an international clinical placement during their pre
registration university education. BACKGROUND: Universities use international
clinical placements, especially in developing countries, to develop cultural
awareness in students; however, little is known about the longer term influences
on students' understandings of global nursing. DESIGN: A retrospective cross
sectional design was used, using an exploratory, descriptive qualitative
approach. METHODS: Individual semi-structured interviews were conducted in 2014
with a purposive sample of 25 pre-registration nursing students from four Western
Australian universities who undertook clinical placements across five countries.
Data were analysed using inductive thematic analysis. RESULTS: Findings highlight
that students developed new understandings around health systems including
fragility of resource access, differences in clinical practice and variances in
nursing roles between settings. Students also experienced challenges but were
able to appreciate alternative world viewpoints. CONCLUSION: International
clinical placements can develop greater awareness and help students form
realistic strategies for using their nursing skills globally. Pre-placement
training in cultural awareness and health system realities, along with strong
supervisory support, is critical to success.
PMID- 28423478
TI - A qualitative study of community nurses' decision-making around the anticipatory
prescribing of end-of-life medications.
AB - AIMS: The aim of this study was to explore community nurses' decision-making
processes around the prescribing of anticipatory medications for people who are
dying. BACKGROUND: Community nurses frequently initiate the prescribing of
anticipatory medications to help control symptoms in those who are dying.
However, little is known about their decision-making processes in relation to
when they instigate anticipatory prescribing and their discussions with families
and General Practitioners. DESIGN: A qualitative interpretive descriptive
enquiry. METHODS: A purposive sample of 11 Community Palliative Nurses and
District Nurses working in one geographical area participated. Data were
collected between March and June 2016 via audio recorded semi-structured
interviews and analysed inductively using Braun and Clarke's thematic analysis.
RESULTS: Three themes were identified: (1) Drugs as a safety net. Anticipatory
medications give nurses a sense of control in last days of life symptom
management; (2) Reading the situation. The nurse judges when to introduce
conversations around anticipatory medications, balancing the need for discussion
with the dying person and their family's likely response; (3) Playing the game.
The nurse owns the decision to initiate anticipatory medication prescribing and
carefully negotiates with the General Practitioner. CONCLUSION: Nurses view pain
control through prescribed medication as key to symptom management for dying
people. Consequently, they own the role of ascertaining when to initiate
discussions with families about anticipatory medicines. Nurses believe they
advocate for dying person and their families' needs and lead negotiations with
General Practitioners for medications to go into the home. This nurse led care
alters the traditional boundaries of the General Practitioners-nurse professional
relationship.
PMID- 28423479
TI - Does a Crossover Age Effect Exist for African American and Hispanic Binge
Drinkers? Findings from the 2010 to 2013 National Study on Drug Use and Health.
AB - BACKGROUND: Among general population studies, lower rates of binge drinking tend
to be found among African Americans and Hispanics compared to Whites. However,
among older adult populations, minority groups have been shown to be at higher
risk for binge drinking, suggesting the presence of a crossover effect from low
to high risk as a function of age. To date, limited research has examined the
crossover effect among African American and Hispanic populations compared to non
Hispanic Whites across large developmental time frames or explored variation in
risk based on income or gender. This study aimed to fill these gaps in the
literature. METHODS: Data were compiled from the 2010 to 2013 National Survey on
Drug Use and Health surveys, which provide annual, nationally representative data
on substance use behaviors among individuals aged 12 and older. Hispanic, non
Hispanic African American, and non-Hispanic White respondents were included (N =
205,198) in the analyses. RESULTS: A crossover effect was found for African
American males and females among the lowest income level (i.e., incomes less than
$20,000). Specifically, after controlling for education and marital status,
compared to Whites, risk for binge drinking was lower for African American males
at ages 18 to 24 and for females at ages 18 to 34, but higher for both African
American males and females at ages 50 to 64. No crossover effect was found for
Hispanic respondents. CONCLUSIONS: Although African Americans are generally at
lower risk for binge drinking, risk appears to increase disproportionately with
age among those who are impoverished. Explanatory factors, such as social
determinants of health prevalent within low-income African American communities
(e.g., lower education, violence exposure, housing insecurity) and potential
areas for intervention programming are discussed.
PMID- 28423480
TI - The effect of high-dose vitamin D supplementation on muscular function and
quality of life in postmenopausal women-A randomized controlled trial.
AB - OBJECTIVE: Observational studies have suggested positive associations between
serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and
quality of life. Our aim was to examine whether high-dose vitamin D
supplementation would improve these measures as compared to standard-dose vitamin
D, as well as the possible muscular effects of single nucleotide polymorphisms
(SNPs) in genes encoding vitamin D-related enzymes. DESIGN: A 12-month
randomized, double-blind, controlled trial where the participants received daily
elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the
participants were randomized to receive either capsules with vitamin D3 (20 000
IU) or matching placebos to be taken twice a week. PATIENTS: A total of 297
postmenopausal women with osteopenia or osteoporosis. MEASUREMENTS: Muscle
strength (handgrip and knee extensor strength), balance (tandem test) and quality
of life (EQ-5D) were measured at baseline and after 12 months. The subjects were
genotyped for SNPs related to vitamin D metabolism. RESULTS: Of the 297 included
women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased
in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate
increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L;
P<.01). There was no significant difference between the groups in change in
muscular strength, balance or quality of life over the intervention period.
Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene)
were associated with muscle strength and treatment effects. CONCLUSION: One-year
treatment with high-dose vitamin D had no effect on muscular strength, balance or
quality of life in postmenopausal women with osteopenia or osteoporosis as
compared to standard dose. The association between rs3829251 and muscle strength
needs confirmation in other populations.
PMID- 28423481
TI - Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia.
AB - Background/Aims: Gastric motility abnormalities have been considered to be
pathophysiological features of functional dyspepsia (FD) that are closely related
to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims
of this study are to (1) investigate the prevalence of gastric motility disorders
and (2) evaluate the association between gastric motility abnormalities and
dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. Methods:
Forty healthy subjects and 94 PDS type FD patients were enrolled in the study.
The volunteers and patients ingested a radiolabeled (technetium-99m) solid test
meal, and scintigraphic images were recorded. Gastric accommodation and emptying
were assessed by scintigraphic imaging. The patients' dyspeptic symptoms were
also explored using self-completed symptom questionnaires with 10 variables (4
scales, 0-3 points) at the same time. Results: In 94 Japanese FD patients, the
prevalence of impaired gastric accommodation and delayed emptying were 14.9%
(14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen
in 25.5% (24/94) of FD patients. There was no association between gastric
motility abnormalities and dyspeptic symptoms. Conclusions: Gastric motility
abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there
was no association between gastric motility abnormalities and dyspeptic symptoms
on gastric scintigraphy.
PMID- 28423482
TI - Clerosterol from vinegar-baked radix bupleuri modifies drug transport.
AB - Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when
combined with traditional chemotherapy and data show that this combination may
modify drug transport. We isolated clerosterol from VBRB and studied its effect
on drug transporters in normal or transporter-overexpressing cells. Transporter
activity was assayed using cellular substrate concentration and transporter
expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake
in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also
decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and
Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects
on Mrp1 protein and gene expression. Further study showed clerosterol increased
OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA.
Clerosterol could suppress Pgp overexpression but not by regulating protein and
gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity
in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active
constituent of VBRB and may work against cancer multidrug resistance by
inhibiting Pgp activity.
PMID- 28423483
TI - MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription
factors (EMT-TFs) and inhibits breast cancer cell migration and invasion.
AB - MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and
progression of cancer metastasis. Here, we analyzed the expression, targets and
functional effects of miR-34a on epithelial to mesenchymal transition-inducing
transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT
inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its
correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is
downregulated in human metastatic breast cancers (MBC) compared to normal breast
tissues and is negatively correlated with clinicopathological features of MBC
patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly
inhibits cell migration and invasion, but exhibits no clear effect on BC cell
growth. We found that miR-34a is able to inactivate EMT signaling pathway with
mediatory of NOTCH1, TWIST1, and ZEB1 upon 3'-UTR activity in MBC cell lines, but
has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the
synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression
of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is
able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in
BT-549 cell line, indicating that they might be a promising therapeutic
combination against breast cancer metastasis. Epigenetic inactivation of the EMT
TFs/miR-34a pathway can potentially alter the equilibrium of these regulations,
facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR
34a alone could serve as a potential therapeutic agent for MBC, and together with
TQ, their therapeutic potential is synergistically enhanced.
PMID- 28423484
TI - miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis
hematopoietic stem/progenitor cells by targeting SOCS6.
AB - Primary myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative
neoplasm characterized by hematopoietic stem cell-derived clonal
myeloproliferation, involving especially the megakaryocyte lineage. To better
characterize how the altered expression of microRNAs might contribute to PMF
pathogenesis, we have previously performed the integrative analysis of gene and
microRNA expression profiles of PMF hematopoietic stem/progenitor cells (HSPCs),
which allowed us to identify miR-494-3p as the upregulated microRNA predicted to
target the highest number of downregulated mRNAs.To elucidate the role of miR-494
3p in hematopoietic differentiation, in the present study we demonstrated that
miR-494-3p enforced expression in normal HSPCs promotes megakaryocytopoiesis.
Gene expression profiling upon miR-494-3p overexpression allowed the
identification of genes commonly downregulated both after microRNA overexpression
and in PMF CD34+ cells. Among them, suppressor of cytokine signaling 6 (SOCS6)
was confirmed to be a miR-494-3p target by luciferase assay. Western blot
analysis showed reduced level of SOCS6 protein as well as STAT3 activation in miR
494-3p overexpressing cells. Furthermore, transient inhibition of SOCS6
expression in HSPCs demonstrated that SOCS6 silencing stimulates
megakaryocytopoiesis, mimicking the phenotypic effects observed upon miR-494-3p
overexpression. Finally, to disclose the contribution of miR-494-3p upregulation
to PMF pathogenesis, we performed inhibition experiments in PMF HSPCs, which
showed that miR-494-3p silencing led to SOCS6 upregulation and impaired
megakaryocyte differentiation.Taken together, our results describe for the first
time the role of miR-494-3p during normal HSPC differentiation and suggest that
its increased expression, and the subsequent downregulation of its target SOCS6,
might contribute to the megakaryocyte hyperplasia commonly observed in PMF
patients.
PMID- 28423485
TI - M2 polarization of macrophages facilitates arsenic-induced cell transformation of
lung epithelial cells.
AB - The alterations in microenvironment upon chronic arsenic exposure may contribute
to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play
an important role in mediating the microenvironment in the lungs. Macrophages
carry out their functions after activation. There are two activation status for
macrophages: classical (M1) or alternative (M2); the latter is associated with
tumorigenesis. Our previous work showed that long-term arsenic exposure induces
transformation of lung epithelial cells. However, the crosstalk between
epithelial cells and macrophages upon arsenic exposure has not been investigated.
In this study, using a co-culture system in which human lung epithelial cells are
cultured with macrophages, we determined that long-term arsenic exposure
polarizes macrophages towards M2 status through ROS generation. Co-culture with
epithelial cells further enhanced the polarization of macrophages as well as
transformation of epithelial cells, while blocking macrophage M2 polarization
decreased the transformation. In addition, macrophage M2 polarization decreased
autophagy activity, which may account for increased cell transformation of
epithelial cells with co-culture of macrophages.
PMID- 28423486
TI - Tick-host conflict: immunoglobulin E antibodies to tick proteins in patients with
anaphylaxis to tick bite.
AB - Tick-borne infectious diseases and allergies are a growing problem worldwide.
Tick bite allergy has been associated with the direct effect of immunoglobulin E
(IgE) response to tick salivary antigens, or secondary to the induction of
allergy to red meat consumption through IgE antibodies against the carbohydrate
alpha-Gal (Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R). However, despite the growing
burden of this pathology, the proteins associated with anaphylaxis to tick bite
have not been characterized. To address this question, a comparative proteomics
approach was used to characterize tick proteins producing an IgE antibody
response in a healthy individual with record of tick bites, which had not
resulted in any allergic reactions, and two patients with anaphylactic reactions
to Rhipicephalus bursa or Hyalomma marginatum tick bites. Both patients and the
healthy individual were red meat tolerant. The results supported a patient
specific IgE antibody response to tick species responsible for the anaphylaxis to
tick bite. Both patients and the healthy individual serologically recognized tick
proteins with and without alpha-Gal modifications, with proteins differentially
recognized by patients but not control sera. These proteins could be used as
potential antigens for diagnostics, treatment and prevention of tick bite-induced
allergies.
PMID- 28423487
TI - Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory
T cells in long-term survivors with advanced melanoma.
AB - Ipilimumab has revolutionized malignant melanoma therapy, but a better
understanding of the mechanisms behind treatment response and adverse effects is
needed. In this work, the immune system of ipilimumab treated patients was
monitored to investigate potential mechanisms of action that may correlate with
treatment outcome. Blood samples from 43 advanced melanoma patients were taken
before, during and at the end of treatment. Hematological parameters were
measured and flow cytometry analysis was performed in fresh samples within two
hours of sample collection. Strong differences in markers CD45RA, CCR7, HLA-DR
and CD15 between fresh and cryopreserved samples were observed. Ipilimumab
treatment increased absolute lymphocyte counts, eosinophils, effector T cells and
their activation status, whilst diminishing the suppressive side of the immune
response, acting on regulatory T cells and myeloid derived suppressor cells
(MDSCs). These effects were visible after one ipilimumab infusion and, regarding
eosinophil counts, correlated with onset of adverse events. Monocytic MDSCs were
decreased in response to treatment only in patients with clinical benefit;
additionally, patients with a lower frequency of these cells after the first
ipilimumab infusion experienced increased overall survival. CD8 effector memory T
cell frequencies at the end of treatment were higher in patients with clinical
benefit and positively correlated with survival. These data show that a clinical
response to ipilimumab not only requires reshaping T cell populations, but
additionally involves a reduction in suppressive cells such as monocytic MDSCs.
Our work could provide insight on predicting treatment outcome, assisting
clinicians in offering the best personalized therapeutic approach.
PMID- 28423488
TI - MMP8 polymorphism is associated with susceptibility to osteonecrosis of the
femoral head in a Chinese Han population.
AB - Osteonecrosis of the femoral head (ONFH) is an orthopedic refractory disease that
adversely affects quality of life. Matrix metalloproteinase-8 (MMP-8) produced by
the bone marrow has been implicated in the degradation of collagen during bone
development. We assessed whether MMP8 polymorphisms are associated with ONFH. In
a case-control study, using chi2 tests and genetic model analyses, we genotyped 5
MMP8 single-nucleotide polymorphisms (SNPs) in 585 ONFH patients and 507 healthy
control subjects in a Chinese Han population. The MMP8 rs11225394 SNP was
associated with an increased risk of ONFH in an allele model (OR=1.34; 95% CI,
1.003-1.786, P=0.047). In addition, rs11225394 was associated with an increased
risk of ONFH in a dominant model (OR =1.39, 95% CI, 1.02-1.89, P=0.036), over
dominant model (OR=1.39, 95% CI, 1.02-1.89, P=0.038), and log-additive model (OR
=1.36, 95% CI, 1.01-1.84, P=0.039). After adjusting for age and gender,
rs11225394 was associated with ONFH in a dominant (OR =1.44, 95% CI, 1.05-1.96,
P=0.023), over-dominant (OR =1.44, 95% CI, 1.05-1.98, P=0.022), and log-additive
model (OR =1.40, 95% CI, 1.04-1.90, P=0.027). These results provide the first
evidence that MMP8 SNP at the rs11225394 locus is associated with the increased
risk of ONFH in Chinese Han population.
PMID- 28423489
TI - Target of obstructive sleep apnea syndrome merge lung cancer: based on big data
platform.
AB - Based on our hospital database, the incidence of lung cancer diagnoses was
similar in obstructive sleep apnea Syndrome (OSAS) and hospital general
population; among individual with a diagnosis of lung cancer, the presence of
OSAS was associated with an increased risk for mortality. In the gene expression
and network-level information, we revealed significant alterations of molecules
related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer
cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway
important in hypoxia-conditioned lung cancer cell. Furthermore, we used publicly
available datasets to validate that the late-stage lung adenocarcinoma patients
showed higher expression HK2 and GBE1 than early-stage ones. In terms of
prognostic features, a survival analysis revealed that the high GBE1 and HK2
expression group exhibited poorer survival in lung adenocarcinoma patients. By
analyzing and integrating multiple datasets, we identify molecular convergence
between hypoxia and lung cancer that reflects their clinical profiles and reveals
molecular pathways involved in hypoxic-induced lung cancer progression. In
conclusion, we show that OSAS severity appears to increase the risk of lung
cancer mortality.
PMID- 28423490
TI - Reappraisal of XRCC1 Arg194Trp polymorphism and glioma risk: a cumulative meta
analysis.
AB - The association between XRCC1 Arg194Trp polymorphism and glioma risk were
inconsistent from published meta-analyses and epidemiological studies. Hence, we
performed this updated and cumulative meta-analysis to reappraisal this
relationship. PubMed, Embase, CBM (Chinese Biomedical Database), and CNKI (China
National Knowledge Internet) databases were comprehensively searched up to August
13, 2016 (updated on December 22, 2016). After study selection and data
extraction from eligible studies, the association was evaluated by odds ratios
(ORs) and its 95% confidence intervals (95%CIs) using Comprehensive Meta-Analysis
software. Finally 16 case-control studies involving 7011 patients and 9519
healthy controls were yielded. The results indicated that XRCC1 Arg194Trp
polymorphism was significantly correlated with the increased risk of glioma [Trp
vs. Arg: OR = 1.18(1.05-1.34); TrpTrp vs. ArgArg: OR = 1.66(1.31-2.12); ArgTrp
vs. ArgArg: OR = 1.34(1.02-1.77); TrpTrp vs. ArgArg+ArgTrp: OR = 1.47(1.26-1.72);
TrpTrp+ArgTrp vs. ArgArg: OR = 1.17(1.01-1.35)]. Cumulative analysis showed the
results changed from non-significant to significant when new studies accumulated,
and sensitivity analysis indicated the results were stable. Subgroup analysis
showed the significant association existed in Asians but not in Caucasians.
Current evidence indicated that XRCC1 Arg194Trp polymorphism was associated with
increased risk for glioma, especially in Asians; however, relevant studies
involving other ethnic groups are required to validate our findings in further.
PMID- 28423491
TI - The miR-25-93-106b cluster regulates tumor metastasis and immune evasion via
modulation of CXCL12 and PD-L1.
AB - The stromal microenvironment controls response to injury and inflammation, and is
also an important determinant of cancer cell behavior. However, our understanding
of its modulation by miRNA (miR) and their respective targets is still sparse.
Here, we identified the miR-25-93-106b cluster and two new target genes as
critical drivers for metastasis and immune evasion of cancer cells. Using miR-25
93-106b knockout mice or antagomiRs, we demonstrated regulation of the production
of the chemoattractant CXCL12 controlling bone marrow metastasis. Moreover, we
identified the immune checkpoint PD-L1 (CD274) as a novel miR-93/106b target
playing a central role in diminishing tumor immunity. Eventually, upregulation of
miR-93 and miR-106b via miR-mimics or treatment with an epigenetic reader domain
(BET) inhibitor resulted in diminished expression of CXCL12 and PD-L1. These data
suggest a potential new therapeutic rationale for use of BET inhibitors for dual
targeting of cancers with strong immunosuppressive and metastatic phenotypes.
PMID- 28423492
TI - ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer
cells.
AB - ONC201 was previously identified as a first-in-class antitumor agent and small
molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing
ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile
and is currently in phase II clinical trials for the treatment of various
malignancies. In the current study, we examine the effect of ONC201 on triple
negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive
to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC
cells that have developed acquired TRAIL resistance. However, TNBC cells that
have developed acquired ONC201 resistance are cross-resistant to TRAIL.
Mechanistically, ONC201 triggers an integrated stress response (ISR) involving
the activation of the transcription factor ATF4. Knockdown of ATF4 impairs ONC201
induced apoptosis of TNBC cells. Importantly, the activation of ATF4 is
compromised in ONC201-resistant TNBC cells. Thus, our results indicate that
ONC201 induces an ISR to cause TNBC cell death and suggest that TNBC patients may
benefit from ONC201-based therapies.
PMID- 28423493
TI - Clinical significance of detecting circulating tumor cells in colorectal cancer
using subtraction enrichment and immunostaining-fluorescence in situ
hybridization (SE-iFISH).
AB - Circulating tumor cells (CTC) are useful in early detection of colorectal cancer.
This study described a newly developed platform, integrated subtraction
enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to
assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44
preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%,
which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033).
No significant association was found between tumor stage, survival and
preoperative CTC number. CTCs were detected in 10 colorectal cancer patients one
week after surgery; seven patients with decreased CTC numbers (compared with
preoperative CTC number) were free of recurrence; whereas two of the three
patients with increased CTC numbers had tumor recurrence. Moreover, CTCs were
detected in 34 colorectal cancer patients three months after surgery; patients
with CTC<2 at three months after surgery had significantly longer Progression
Free Survival than those with CTC>=2 (P=0.019); patients with decreased CTC
number (compared with preoperative CTC number) had significantly longer
Progression Free Survival than those with increased CTC number (P=0.003). In
conclusion, CTCs could be detected in various stages of colorectal cancer using
SE-iFISH. Dynamic monitoring of CTC numbers could predict recurrence and
prognosis.
PMID- 28423494
TI - Control of long-distance cell-to-cell communication and autophagosome transfer in
squamous cell carcinoma via tunneling nanotubes.
AB - Tunneling nanotubes (TnTs) are thin channels that temporally connect nearby cells
allowing the cell-to-cell trafficking of biomolecules and organelles. The
presence or absence of TnTs in human neoplasms and the mechanisms of TnT assembly
remains largely unexplored. In this study, we have identified TnTs in tumor cells
derived from squamous cell carcinomas (SCC) cultured under bi-dimensional and tri
dimensional conditions and also in human SCC tissues. Our study demonstrates that
TnTs are not specific of epithelial or mesenchymal phenotypes and allow the
trafficking of endosomal/lysosomal vesicles, mitochondria, and autophagosomes
between both types of cells. We have identified focal adhesion kinase (FAK) as a
key molecule required for TnT assembly via a mechanism involving the MMP-2
metalloprotease. We have also found that the FAK inhibitor PF-562271, which is
currently in clinical development for cancer treatment, impairs TnT formation.
Finally, FAK-deficient cells transfer lysosomes/autophagosomes to FAK-proficient
cells via TnTs which may represent a novel mechanism to adapt to the stress
elicited by impaired FAK signaling. Collectively, our results strongly suggest a
link between FAK, MMP-2, and TnT, and unveil new vulnerabilities that can be
exploited to efficiently eradicate cancer cells.
PMID- 28423495
TI - Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting
cancer stem cells.
AB - The dismal prognosis of locally advanced and metastatic squamous cell carcinoma
of the head and neck (HNSCC) is primarily due to the development of resistance to
chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor
(EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival,
cancer stem cells (CSCs), and resistance to CRT. Here we investigated the
radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro
and in vivo. Our results showed strong antiproliferative effects of afatinib in
HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial
cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects
with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in
vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to
epithelial transition, G1 cell cycle arrest, and the attenuating ionizing
radiation (IR)-induced activation of DNA double strand break repair (DSB)
ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on
tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and
decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we
observed that a combination of afatinib with IR significantly reduced SCC1
xenograft tumors (median weight of 168.25 +/- 20.85 mg; p = 0.05) compared to
afatinib (280.07 +/- 20.54 mg) or IR alone (324.91 +/- 28.08 mg).
Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation
of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated
gammaH2AX by afatinib. Overall, afatinib reduces tumorigenicity and
radiosensitizes HNSCC cells. It holds promise for future clinical development as
a novel radiosensitizer by improving CSC eradication.
PMID- 28423496
TI - mTOR inhibitors activate PERK signaling and favor viability of gastrointestinal
neuroendocrine cell lines.
AB - mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently
activated in cancer cells. The mTOR pathway has been shown to be up-regulated in
most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known
about the UPR status in neoplastic neuroendocrine cells. However, these hormone
producing cells are likely to present distinctive adaptations of this pathway, as
other secretory cells. We therefore analyzed the status of the three axes of UPR
and their relation to mTOR pathway in two gastrointestinal neuroendocrine tumors
(GI-NET) cell lines STC-1 and GluTag. At baseline, pharmacological inducers
activate the three arms of UPR: PERK, ATF6 and IRE1. Although hypoxia stimulates
the PERK, ATF6 and IRE-1 pathways in both cell lines, glucose depletion activates
UPR only in STC-1 cell line. Strikingly, P-p70S6K1 increases concomitantly to P
PERK and BiP in response to thapsigargin treatment, glucose depletion or hypoxia.
We found that different mTOR inhibitors activate the PERK signaling pathway. To
confirm that mTOR inhibition modulates PERK activation, we inhibited PERK and
showed that it decreased cell viability when associated to mTOR inhibition,
indicating that mTOR drives a PERK-dependent survival pathway. In conclusion, in
GI-NET cell lines, UPR signaling is functional and PERK arm is induced by mTOR
inhibition. These observations open up new perspectives for therapeutic
strategies: the crosstalk between mTOR and UPR might contribute to the resistance
to mTOR inhibitors and could be targeted by mTOR and PERK inhibitors in
combination therapy.
PMID- 28423497
TI - Drp1-dependent mitophagy protects against cisplatin-induced apoptosis of renal
tubular epithelial cells by improving mitochondrial function.
AB - Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients.
There is increasing evidence that mitochondrial dysfunction plays an important
role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is
carried out by mitophagy. Although mitophagy is considered of particular
importance in protecting against AKI, little is known of the precise role of
mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity.
Also, evidence that activation of mitophagy improved mitochondrial function is
lacking. Furthermore, several evidences have shown that mitochondrial fission
coordinates with mitophagy. The aim of this study was to investigate whether
activation of mitophagy protects against mitochondrial dysfunction and renal
proximal tubular cells injury during cisplatin treatment. The effect of
mitochondrial fission on mitophagy was also investigated. In cultured human renal
proximal tubular cells, we observed that 3-methyladenine, a pharmacological
inhibitor of autophagy, blocked mitophagy and exacerbated cisplatin-induced
mitochondrial dysfunction and cells injury. In contrast, autophagy activator
rapamycin enhanced mitophagy and protected against the harmful effects of
cisplatin on mitochondrial function and cells viability. Suppression of
mitochondrial fission by knockdown of its main regulator dynamin-related protein
1 (Drp1) decreased cisplatin-induced mitophagy. Meanwhile, Drp1 suppression
protected against cisplatin-induced cells injury by inhibiting mitochondrial
dysfunction. Our results provide evidence that Drp1-depedent mitophagy has
potential as renoprotective targets for the treatment of cisplatin-induced AKI.
PMID- 28423498
TI - The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid
invasiveness.
AB - Tumor metastasis profoundly reduces the survival of breast cancer patients, but
the mechanisms underlying breast cancer invasiveness and metastasis are
incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts
in a sumoylation-dependent manner to suppress the invasive behavior of MDA-MB-231
human breast cancer cell-derived organoids. We also find that the SUMO E3 ligase
PIAS3 inhibits the invasive growth of breast cancer cell-derived organoids. In
mechanistic studies, PIAS3 maintains breast cancer organoids in a non-invasive
state via sumoylation of Smurf2. Importantly, the E3 ubiquitin ligase activity is
required for sumoylated Smurf2 to suppress the invasive growth of breast cancer
cell derived organoids. Collectively, our findings define a novel role for the
PIAS3-Smurf2 sumoylation pathway in the suppression of breast cancer cell
invasiveness. These findings lay the foundation for the development of novel
biomarkers and targeted therapeutic approaches in breast cancer.
PMID- 28423499
TI - Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic
fibrosis via Akt-Nrf2-Smad2/3 signaling pathway.
AB - Liver fibrosis is a global health problem and its relationship with imidazoline
I2 receptor has not been reported. This study aimed to investigate the effects
and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan
(IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver
fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight
weeks, and in vitro studies were performed on activated LX2 cells treated with
transforming growth factor-beta (TGF-beta). Our results showed that IDA
significantly improved liver inflammation, ameliorated hepatic stellate cells
activation and reduced collagen accumulation by suppressing the pro-fibrogenic
signaling of TGF-beta/Smad. Further investigation showed that IDA significantly
balanced oxidative stress through improving the expressions and activities of
anti-oxidant and detoxifying enzymes and activating Nrf2-the key defender against
oxidative stress with anti-fibrotic potentials. Even more impressively, knock out
of Nrf2 or suppression of Akt by perifosine (PE) eliminated the anti-oxidant and
anti-fibrotic effects of IDA in vivo and in vitro, suggesting that Akt/Nrf2
constitutes a critical component of IDA's protective functions. Taken together,
IDA exhibits potent effects against liver fibrosis via Akt-Nrf2-Smad2/3 signaling
pathway, which suggests that specifically targeting I2R may be a potentially
useful therapeutic strategy for liver fibrosis.
PMID- 28423500
TI - The role of hesperetin on osteogenesis of human mesenchymal stem cells and its
function in bone regeneration.
AB - Hesperetin has been suggested to be involved in bone strength. We aimed to
investigate the effects of hesperetin on the osteogenic differentiation of human
mesenchymal stem cells and its related mechanisms. We showed that hesperetin
promoted osteogenic differentiation of human mesenchymal stem cells in vitro. It
potentially exerts its effects via the ERK and Smad signaling pathways. Using a
rat osteotomy model, we showed that human mesenchymal stem cells combined with a
hesperetin/gelatin sponge scaffold resulted in accelerated fracture healing in
vivo. Due to the low cost of hesperetin, it could be used as a growth factor for
bone tissue engineering or surgical fracture treatment.
PMID- 28423501
TI - Epigenetic silencing of miR-520c leads to induced S100A4 expression and its
mediated colorectal cancer progression.
AB - The S100 calcium-binding protein A4 (S100A4) induces epithelial mesenchymal
transition, migration, invasion, angiogenesis and metastasis. Its induced
expression in several cancer types correlates with poor prognosis. Apart from the
functional and transcriptional regulatory aspects of S100A4, its post
transcriptional regulation is not yet clearly elucidated. In this study, we show
that microRNAs (miR) miR-505-5p and miR-520c-3p target the 3'-UTR of S100A4 and
inhibits its expression and its mediated migration and invasion. 5-Aza treatment
significantly increased miR-520c-3p expression and reduced the S100A4 protein
amounts. The upstream promoter region of miR-520c is hypermethylated irrespective
of the metastasis status of colorectal cancer (CRC) patient tissues and in all
analyzed CRC cell lines. Moreover, in a cohort of CRC patient specimen (n = 59),
miR-520c-3p was significantly downregulated. miR-520c-3p stably expressing HCT116
cells showed a reduced metastasis formation in livers after implanting in mice
spleen. Taken together, our findings demonstrate that S100A4 is post
transcriptionally regulated by tumor suppressor miRs, miR-505c-5p and miR-520c
3p, and particularly miR-520c-3p expression is epigenetically silenced in CRC.
PMID- 28423502
TI - Acute lymphoblastic leukemia cells are sensitive to disturbances in protein
homeostasis induced by proteasome deubiquitinase inhibition.
AB - The non-genotoxic nature of proteasome inhibition makes it an attractive
therapeutic option for the treatment of pediatric malignancies. We recently
described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase
(DUB) activity that induces proteotoxic stress and apoptosis in cancer cells.
Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive
to treatment with VLX1570, resulting in the accumulation of polyubiquitinated
proteasome substrates and loss of cell viability. VLX1570 treatment increased the
levels of a number of proteins, including the chaperone HSP70B', the oxidative
stress marker heme oxygenase-1 (HO-1) and the cell cycle regulator p21Cip1.
Unexpectedly, polybiquitin accumulation was found to be uncoupled from ER stress
in ALL cells. Thus, increased phosphorylation of eIF2alpha occurred only at supra
pharmacological VLX1570 concentrations and did not correlate with polybiquitin
accumulation. Total cellular protein synthesis was found to decrease in the
absence of eIF2alpha phosphorylation. Furthermore, ISRIB (Integrated Stress
Response inhibitor) did not overcome the inhibition of protein synthesis. We
finally show that VLX1570 can be combined with L-asparaginase for additive or
synergistic antiproliferative effects on ALL cells. We conclude that ALL cells
are highly sensitive to the proteasome DUB inhibitor VLX1570 suggesting a novel
therapeutic option for this disease.
PMID- 28423503
TI - Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of
adriamycin in a gold nanoshell-based drug/gene co-delivery system.
AB - Rap2b is a novel p53 target we have identified recently. Knockdown of Rap2b
sensitizes HCT116 cells to adriamycin-induced apoptosis, indicating that Rap2b
promotes adriamycin resistance in cancer cells. In the present study, we designed
a nanostructure-based drug/gene delivery system to evaluate the potential of
Rap2b siRNA as a therapeutic agent against human cancers. Specifically, after co
incubated with HCT116 cells, adriamycin- and Rap2b siRNA-loaded gold nanoshells
were internalized. Subsequent laser irradiation promoted release of adriamycin
and Rap2b siRNA from the nanoparticles. The laser-induced release of Rap2b siRNA
decreased cellular expression of Rap2b and significantly enhanced the anticancer
therapeutic efficacy of adriamycin in vitro and in vivo. In addition, laser
irradiation of the nanoparticles might exert an additional thermal killing effect
on cancer cells and further improved the anticancer efficacy of adriamycin. In
summary, Rap2b siRNA is a potential enhancing agent for adriamycin-based
anticancer therapeutics and the gold nanoshell-based drug/gene delivery system
carrying both adriamycin and Rap2b siRNA provides a promising anticancer
therapeutic strategy.
PMID- 28423504
TI - Variations in the bitterness perception-related genes TAS2R38 and CA6 modify the
risk for colorectal cancer in Koreans.
AB - Bitterness perception is known to be an important factor in individuals' dietary
behaviors and is also associated with the sensing of nutritious/noxious molecules
for subsequent metabolic responses in multiple organs. Therefore, the genetic
variation in bitterness sensing may be associated with diet-related diseases,
including colorectal cancer (CRC). We investigated the influence of variations in
the bitterness-sensing genes taste receptor type 2 member 38 (TAS2R38) and
carbonic anhydrase 6 (CA6) on the consumption of food, tobacco and alcohol and
the risk of CRC in Koreans. The study population consisted of 681 cases and 1361
controls, and their intake of vegetables, fruits, fiber, fat-food and sweets was
analyzed. The genotypes for TAS2R38 A49P, V262A and I296V and CA6 rs2274333 A/G
were assessed using the MassArray technique. Our findings suggested that the
TAS2R38 diplotype, CA6 rs2274333 and their combined genotype had a negligible
influence on dietary and alcohol intake. The combined TAS2R38-CA6 AVI/AVI-AA
genotype was associated with higher tobacco consumption than the other genotypes
in CRC cases only. However, the genetic variations were a significant risk factor
for CRC. The TAS2R38 AVI/AVI diplotype and CA6 G allele were associated with a
reduced risk of CRC. Moreover, when the combined genotypes of the subjects were
analyzed, possessing both the variant diplotype/variant allele (AVI/AVI+G*) was
associated with a greater reduction in the risk of CRC (adjusted OR = 0.49;
95%CI: 0.34-0.74). In summary, variations in the bitterness perception genes
TAS2R38 and CA6 did not influence the examined food intake in Koreans. However,
those genetic variants were a decisive modifying factor of CRC susceptibility.
PMID- 28423505
TI - Identification and analysis of mutational hotspots in oncogenes and tumour
suppressors.
AB - BACKGROUND: The key to interpreting the contribution of a disease-associated
mutation in the development and progression of cancer is an understanding of the
consequences of that mutation both on the function of the affected protein and on
the pathways in which that protein is involved. Protein domains encapsulate
function and position-specific domain based analysis of mutations have been shown
to help elucidate their phenotypes. RESULTS: In this paper we examine the domain
biases in oncogenes and tumour suppressors, and find that their domain
compositions substantially differ. Using data from over 30 different cancers from
whole-exome sequencing cancer genomic projects we mapped over one million
mutations to their respective Pfam domains to identify which domains are enriched
in any of three different classes of mutation; missense, indels or truncations.
Next, we identified the mutational hotspots within domain families by mapping
small mutations to equivalent positions in multiple sequence alignments of
protein domainsWe find that gain of function mutations from oncogenes and loss of
function mutations from tumour suppressors are normally found in different domain
families and when observed in the same domain families, hotspot mutations are
located at different positions within the multiple sequence alignment of the
domain. CONCLUSIONS: By considering hotspots in tumour suppressors and oncogenes
independently, we find that there are different specific positions within domain
families that are particularly suited to accommodate either a loss or a gain of
function mutation. The position is also dependent on the class of mutation.We
find rare mutations co-located with well-known functional mutation hotspots, in
members of homologous domain superfamilies, and we detect novel mutation hotspots
in domain families previously unconnected with cancer. The results of this
analysis can be accessed through the MOKCa database
(http://strubiol.icr.ac.uk/extra/MOKCa).
PMID- 28423506
TI - Granulocyte colony-stimulating factor enhances the therapeutic efficacy of bone
marrow mesenchymal stem cell transplantation in rats with experimental acute
pancreatitis.
AB - INTRODUCTION: Acute pancreatitis (AP) is one of the most common diseases
involving necrotic inflammation. Bone marrow mesenchymal stem cells (BMMSCs) have
the potential of multi-directional differentiation and self-renewal for tissue
repair. It remains less clear if granulocyte colony-stimulating factor (G-CSF)
can improve the therapeutic effect of BMMSC transplant in AP. Therefore, we
explored this issue in a rat model of experimental AP. RESULTS: Transplanted
PKH26-positive BMMSCs were present in the injured pancreatic tissue, with some
cells co-expressed pancreatic cellular markers, including Pax-4, Ngn3 and Nkx-6.
Pathological, biochemical and serological data suggested an improvement in
histological and functional recovery in these animals relative to control.
Overall, the AP model rats received BMMSCs and G-CSF co-treatment showed better
recovery in terms of tissue regeneration and blood biochemical levels relative to
other groups. MATERIALS AND METHODS: BMMSCs from donor rats were labeled with the
fluorescent dye PKH26 and transfused into recipient rats with AP induced by L
arginine. The animals were divided into a control group, and groups treated with
BMMSCs, G-CSF, and BMMSCs together with G-CSF. Therapeutic effects were evaluated
histologically with immunohistochemistry and immunofluorescence, together with
biochemical measurement of pancreatic markers. CONCLUSION: G-CSF therapy with
BMMSC transplantation improves histological and functional outcomes in rats with
experimental AP.
PMID- 28423507
TI - TGF-beta-independent CTGF induction regulates cell adhesion mediated drug
resistance by increasing collagen I in HCC.
AB - Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutic
agents and remains an unmet medical need. Here, we demonstrate a mechanism of
cell adhesion-mediated drug resistance using a variety of HCC spheroid models to
overcome environment-mediated drug resistance in HCC. We classified spheroids
into two groups, tightly compacted and loosely compacted aggregates, based on
investigation of dynamics of spheroid formation. Our results show that
compactness of HCC spheroids correlated with fibroblast-like characteristics,
collagen 1A1 (COL1A1) content, and capacity for chemoresistance. We also showed
that ablation of COL1A1 attenuated not only the capacity for compact-spheroid
formation, but also chemoresistance. Generally, connective tissue growth factor
(CTGF) acts downstream of transforming growth factor (TGF)-beta and promotes
collagen I fiber deposition in the tumor microenvironment. Importantly, we found
that TGF-beta-independent CTGF is upregulated and regulates cell adhesion
mediated drug resistance by inducing COL1A1 in tightly compacted HCC spheroids.
Furthermore, losartan, which inhibits collagen I synthesis, impaired the
compactness of spheroids via disruption of cell-cell contacts and increased the
efficacy of anticancer therapeutics in HCC cell line- and HCC patient-derived
tumor spheroids. These results strongly suggest functional roles for CTGF-induced
collagen I expression in formation of compact spheroids and in evading anticancer
therapies in HCC, and suggest that losartan, administered in combination with
conventional chemotherapy, might be an effective treatment for liver cancer.
PMID- 28423508
TI - Annexin A13 promotes tumor cell invasion in vitro and is associated with
metastasis in human colorectal cancer.
AB - PURPOSE: Aberrantly upregulated expression of selected members of annexin, a
group of calcium- and membrane-binding proteins, have been found to be associated
with metastasis, poor prognosis, and other clinical characteristics in colorectal
cancer (CRC), the third most diagnosed cancer. However, ANXA13 (encoding protein
annexin A13), the original founder gene of the annexin A family, has not been
studied carefully as a potential prognostic biomarker in CRC. METHODS: The
protein level of annexin A13 was determined by western blot in a panel of CRC
cell lines. Tumor cell invasion was determined by a Matrigel in vitro invasion
assay in selected CRC cells with either upregulated (via plasmid transfection) or
downregulated (via siRNA treatment) expression of ANXA13. The clinicopathological
features and prognostic values associated with ANXA13 expression were also
evaluated in a group of 125 CRC patients. RESULTS: ANXA13 was expressed at a high
level in HCT116 and HT29 cells but undetected or at a lower level in SW620, SW48,
and Rko cells. CRC cell invasion was promoted by ANXA13 overexpression in SW620
or Rko cells and was reduced by ANXA13 downregulation in HCT116 or HT29 cells. In
CRC patients, ANXA13 expression levels correlated with lymph node metastasis and
were associated with poor overall survival. CONCLUSIONS: ANXA13 is associated
with CRC cell invasion in vitro, and with lymph node metastasis and poor survival
in CRC patients. Our results indicate that ANXA13 can be exploited as a biomarker
for its diagnostic and prognostic values.
PMID- 28423509
TI - Histone lysine methyltransferase G9a is a novel epigenetic target for the
treatment of hepatocellular carcinoma.
AB - Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone
lysine methyltransferase G9a and is associated with the repression of
transcription. However, both the role of G9a and the significance of H3K9me2 in
hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted
loss-of-function assay of G9a using short-hairpin RNA and pharmacological
interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell
growth and sphere formation. However, transforming growth factor beta1-induced
epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown.
Combined analyses of chromatin immunoprecipitation followed by sequencing and RNA
sequencing led to successful identification of 96 candidate epigenetic targets of
G9a. Pharmacological inhibition of G9a by BIX-01294 resulted in both cell growth
inhibition and induction of apoptosis in HCC cells. Intraperitoneal
administration of BIX-01294 suppressed the growth of xenograft tumors generated
by implantation of HCC cells in non-obese diabetic/severe combined
immunodeficient mice. Immunohistochemical analyses revealed high levels of G9a
and H3K9me2 in 36 (66.7%) and 35 (64.8%) primary HCC tissues, respectively. G9a
expression levels were significantly positively correlated with H3K9me2 levels in
tumor tissues. In contrast, in non-tumor tissues, G9a and H3K9me2 were only
observed in biliary epithelial cells and periportal hepatocytes. In conclusion,
G9a inhibition impairs anchorage-dependent and -independent cell growth, but not
EMT in HCC cells. Our data indicate that pharmacological interference of G9a
might be a novel epigenetic approach for the treatment of HCC.
PMID- 28423510
TI - Genistein inhibits the growth and regulates the migration and invasion abilities
of melanoma cells via the FAK/paxillin and MAPK pathways.
AB - Genistein is one of the main components of soy-based foods, which are widely
known for their many benefits, including anti-cancer, anti-inflammatory, and
antioxidant effects. In this study, we investigated the anti-metastasis effects
of genistein on B16F10 melanoma cells. Our results showed that genistein strongly
inhibited B16F10 cell proliferation and induced apoptosis in time- and
concentration-dependent manners. Genistein altered the morphology of B16F10 cells
to an elongated shape with slim pseudopodia-like protrusions. Moreover, genistein
inhibited the invasion and migration abilities of B16F10 cells in a dose
dependent manner. On one hand, a high concentration of genistein (100 MUM)
significantly inhibited cell adhesion and migration, as shown by wound healing
assays and transwell-migration and invasion assays. Furthermore, the expression
levels of p-FAK, p-paxillin, tensin-2, vinculin, and alpha-actinin were decreased
by genistein. As a result, genistein is believed to strongly downregulate the
migration and invasion abilities of B16F10 cells via the FAK/paxillin pathway.
Moreover, p-p38, p-ERK, and p-JNK levels were also dramatically decreased by
treatment with genistein. Finally, genistein significantly decreased the gene
expression of FAK, paxillin, vimentin, and epithelial-to-mesenchymal transition
related transcription factor Snail, as shown by real-time PCR (qPCR) analysis. On
the other hand, a lower concentration of genistein (12.5 MUM) significantly
promoted both invasion and migration by activating the FAK/paxillin and MAPK
signaling cascades. Taken together, this study showed for the first time that
genistein exerts dual functional effects on melanoma cells. Our findings suggest
that genistein regulates the FAK/paxillin and MAPK signaling pathways in a highly
concentration-dependent manner. Patients with melanoma should therefore be
cautious of consuming soy-based foods in their diets.
PMID- 28423511
TI - ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression
and autophagy.
AB - The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition
in cancer therapy is tempered by the identification of new emerging functions of
ATM, which suggests that the role of this protein in cancer progression is
complex. We recently demonstrated that this tumor suppressor gene could act as
tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2)
positive breast cancer. Herein we put in evidence that ATM expression sustains
the proportion of cells with a stem-like phenotype, measured as the capability to
form mammospheres, independently of HER2 expression levels. Transcriptomic
analyses revealed that, in mammospheres, ATM modulates the expression of cell
cycle-, DNA repair- and autophagy-related genes. Among these, the silencing of
the autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs
mammosphere formation similarly to ATM depletion. Conversely, ATG4C ectopic
expression in cells silenced for ATM expression, rescues mammospheres growth.
Finally, tumor array analyses, performed using public data, identify a
significant correlation between ATM and ATG4C expression levels in all human
breast cancer subtypes, except for the basal-like one.Overall, we uncover a new
connection between ATM kinase and autophagy regulation in breast cancer. We
demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of
mammosphere formation, suggesting that their targeting may improve current
approaches to eradicate breast cancer cells with a stem-like phenotype.
PMID- 28423512
TI - Kinase analysis of penile squamous cell carcinoma on multiple platforms to
identify potential therapeutic targets.
AB - Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly
understood biology and suboptimal systemic therapy. Given that kinases may be
drivers and readily actionable, we performed comprehensive multiplatform analysis
of kinases in PSCC tumor and normal tissue. Fresh frozen tumors were collected
from 11 patients with PSCC. After macrodissection to demarcate tumor from normal
tissue, the samples underwent multiplatform analysis of kinases. Next Generation
Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture
and run on the Illumina MiSeq at PE150bp. The NanoString nCounter(r) platform
analyzed the expression of 519 kinase genes. Kinase activity of tissue lysates
was measured using PamStation(r)12 high-content phospho-peptide substrate
microarray system. Network mapping was done with GeneGo MetaCoreTM and upstream
kinase prediction was performed with BioNavigator and the Kinexus database.
Ingenuity pathway analysis was performed to integrate elevated kinase activity
and gene over-expression with coexisting missense mutations at DNA level. Top
pathways upregulated in both the kinase activity and gene expression platforms
were PTEN, STAT3, GNRH, IL-8 and B cell receptor signaling. Potentially relevant
missense mutations were seen in 176 kinase genes, with the top altered pathways
overlapping with gene overexpression being GNRH, NF-kB and STAT3 signaling.
ERBB2, ERBB3 and SYK were altered on NGS and also exhibited elevated kinase
activity. To summarize, multiplatform comprehensive analysis of kinases
discovered potential drivers of PSCC and actionable therapeutic targets.
Translational studies are necessary to validate the functional relevance of our
data to make advances in this rare malignancy.
PMID- 28423513
TI - miR-503-5p confers drug resistance by targeting PUMA in colorectal carcinoma.
AB - The development of multidrug-resistance (MDR) is a major contributor to death in
colorectal carcinoma (CRC). Here, we investigated the possible role of microRNA
(miR)-503-5p in drug resistant CRC cells. Unbiased microRNA array screening
revealed that miR-503-5p is up-regulated in two oxaliplatin (OXA)-resistant CRC
cell lines. Overexpression of miR-503-5p conferred resistance to OXA-induced
apoptosis and inhibition of tumor growth in vitro and in vivo through down
regulation of PUMA expression. miR-503-5p knockdown sensitized chemoresistant CRC
cells to OXA. Our studies indicated that p53 suppresses miR-503-5p expression and
that deletion of p53 upregulates miR-503-5p expression. Inhibition of miR-503-5p
in p53 null cells increased their sensitivity to OXA treatment. Importantly,
analysis of patient samples showed that expression of miR-503-5p negatively
correlates with PUMA in CRC. These results indicate that a p53/miR-503-5p/PUMA
signaling axis regulates the CRC response to chemotherapy, and suggest that miR
503-5p plays an important role in the development of MDR in CRC by modulating
PUMA expression.
PMID- 28423514
TI - Mitotic read-out genes confer poor outcome in luminal A breast cancer tumors.
AB - Luminal breast tumors have been classified into A and B subgroups, with the
luminal A being associated with a more favorable clinical outcome. Unfortunately,
luminal A tumors do not have a universally good prognosis. We used transcriptomic
analyses using public datasets to evaluate the differential expression between
normal breast tissue and breast cancer, focusing on upregulated genes included in
cell cycle function. Association of selected genes with relapse free survival
(RFS) and overall survival (OS) was performed using the KM Plotter Online Tool
(http://www.kmplot.com). Seventy-seven genes were differentially expressed
between normal and malignant breast tissue. Only five genes were associated with
poor RFS and OS. The mitosis-related genes GTSE1, CDCA3, FAM83D and SMC4 were
associated with poor outcome specifically in Luminal A tumors. The combination of
FAM83D and CDCA3 for RFS and GTSE1 alone for OS showed the better prediction for
clinical outcome. CDCA3 was amplified in 3.4% of the tumors, and FAM83D and SMC4
in 2.3% and 2.2%, respectively. In conclusion, we describe a set of genes that
predict detrimental outcome in Luminal A tumors. These genes may have utility for
stratification in trials of antimitotic agents or cytotoxic chemotherapy, or as
candidates for direct target inhibition.
PMID- 28423515
TI - Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual
PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma.
AB - Glioblastoma (GBM) is an ideal candidate disease for signal transduction targeted
therapy because the majority of these tumors harbor genetic alterations that
result in aberrant activation of growth factor signaling pathways. Loss of
heterozygosity of chromosome 10, mutations in the tumor suppressor gene PTEN, and
PI3K mutations are molecular hallmarks of GBM and indicate poor prognostic
outcomes in many cancers. Consequently, inhibiting the PI3K pathway may provide
therapeutic benefit in these cancers. PI3K inhibitors generally block
proliferation rather than induce apoptosis. To restore the sensitivity of GBM to
apoptosis induction, targeted agents have been combined with conventional
therapy. However, the molecular heterogeneity and infiltrative nature of GBM make
it resistant to traditional single agent therapy. Our objectives were to test a
dual PI3K/mTOR inhibitor that may cross the blood-brain barrier (BBB) and provide
the rationale for using this inhibitor in combination regimens to chemotherapy
induced synergism in GBM. Here we report the preclinical potential of a novel,
orally bioavailable PI3K/mTOR dual inhibitor, DS7423 (hereafter DS), in in-vitro
and in-vivo studies. DS was tested in mice, and DS plasma and brain
concentrations were determined. DS crossed the BBB and led to potent suppression
of PI3K pathway biomarkers in the brain. The physiologically relevant
concentration of DS was tested in 9 glioma cell lines and 22 glioma-initiating
cell (GIC) lines. DS inhibited the growth of glioma tumor cell lines and GICs at
mean 50% inhibitory concentration values of less than 250 nmol/L. We found that
PI3K mutations and PTEN alterations were associated with cellular response to DS
treatment; with preferential inhibition of cell growth in PI3KCA-mutant and PTEN
altered cell lines. DS showed efficacy and survival benefit in the U87 and GSC11
orthotopic models of GBM. Furthermore, administration of DS enhanced the
antitumor efficacy of temozolomide against GBM in U87 glioma models, which shows
that PI3K/mTOR inhibitors may enhance alkylating agent-mediated cytotoxicity,
providing a novel regimen for the treatment of GBM. Our present findings
establish that DS can specifically be used in patients who have PI3K pathway
activation and/or loss of PTEN function. Further studies are warranted to
determine the potential of DS for glioma treatment.
PMID- 28423516
TI - The addition of celecoxib improves the antitumor effect of cetuximab in
colorectal cancer: role of EGFR-RAS-FOXM1-beta- catenin signaling axis.
AB - Here we showed that the addition of the COX-2 inhibitor celecoxib improved the
antitumor efficacy in colorectal cancer (CRC) of the monoclonal anti-EGFR
antibody cetuximab. The addition of celecoxib augmented the efficacy of cetuximab
to inhibit cell proliferation and to induce apoptosis in CRC cells. Moreover, the
combination of celecoxib and cetuximab was more effective than either treatment
alone in reducing the tumor volume in a mouse xenograft model. The combined
treatment enhanced the inhibition of EGFR signaling and altered the subcellular
distribution of beta-catenin. Moreover, knockdown of FOXM1 showed that this
transcription factor participates in this enhanced antitumoral response. Besides,
the combined treatment decreased beta-catenin/FOXM1 interaction and reduced the
cancer stem cell subpopulation in CRC cells, as indicated their diminished
capacity to form colonospheres. Notably, the inmunodetection of FOXM1 in the
nuclei of tumor cells in human colorectal adenocarcinomas was significantly
associated with response of patients to cetuximab. In summary, our study shows
that the addition of celecoxib enhances the antitumor efficacy of cetuximab in
CRC due to impairment of EGFR-RAS-FOXM1-beta-catenin signaling axis. Results also
support that FOXM1 could be a predictive marker of response of mCRC patients to
cetuximab therapy.
PMID- 28423517
TI - Next generation sequencing of extraskeletal myxoid chondrosarcoma.
AB - Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated
soft tissue sarcoma with a high propensity for metastases. Using a clinical
sequencing approach, we genomically profiled patients with metastatic EMC to
elucidate the molecular biology and identify potentially actionable mutations. We
also evaluated potential predictive factors of benefit to sunitinib, a multi
targeted tyrosine kinase inhibitor with reported activity in a subset of EMC
patients. Between January 31, 2012 and April 15, 2016, six patients with EMC
participated in the clinical sequencing research study. High quality DNA and RNA
was isolated and matched normal samples underwent comprehensive next generation
sequencing (whole or OncoSeq capture exome of tumor and normal, tumor PolyA+ and
capture transcriptome). The expression levels of sunitinib targeted-kinases were
measured by transcriptome sequencing for KDR, PDGFRA/B, KIT, RET, FLT1, and FLT4.
The previously reported EWSR1-NR4A3 translocation was identified in all patient
tumors; however, other recurring genomic abnormalities were not detected. RET
expression was significantly greater in patients with EMC relative to other types
of sarcomas except for liposarcoma (p<0.0002). The folate receptor was
overexpressed in two patients. Our study demonstrated that similar to other
translocation-associated sarcomas, the mutational profile of metastatic EMC is
limited beyond the pathognomonic translocation. The clinical significance of RET
expression in EMC should be explored. Additional pre-clinical investigations of
EMC may help elucidate molecular mechanisms contributing to EMC tumorigenesis
that could be translated to the clinical setting.
PMID- 28423518
TI - A novel pathogenic splice acceptor site germline mutation in intron 14 of the APC
gene in a Chinese family with familial adenomatous polyposis.
AB - Familial adenomatous polyposis (FAP) is an autosomal dominant precancerous
condition, clinically characterized by the presence of multiple colorectal
adenomas or polyps. Patients with FAP has a high risk of developing colorectal
cancer (CRC) from these colorectal adenomatous polyps by the mean age of
diagnosis at 40 years. Germline mutations of the APC gene cause familial
adenomatous polyposis (FAP). Colectomy has recommended for the FAP patients with
significant polyposis. Here, we present a clinical molecular study of a four
generation Chinese family with FAP. Clinical diagnosis of FAP has been done
according to the phenotype, family history and medical records. Patient's blood
samples were collected and genomic DNA was extracted. In order to identify the
pathogenic mutation underlying the disease phenotype targeted next-generation
sequencing and confirmatory sanger sequencing has undertaken. Targeted next
generation sequencing identified a novel heterozygous splice-acceptor site
mutation [c.1744-1G>A] in intron 14 of APC gene, which is co-segregated with the
FAP phenotypes in the proband and amongst all the affected family members. This
mutation is not present in unaffected family members and in normal healthy
controls of same ethnic origin. According to the LOVD database for Chinese
colorectal cancer patients, in Chinese population, 60% of the previously reported
APC gene mutations causes FAP, are missense mutations. This novel splice-acceptor
site mutation causing FAP in this Chinese family expands the germline mutation
spectrum of the APC gene in the Chinese population.
PMID- 28423519
TI - Vitamin D and VDR in cancer cachexia and muscle regeneration.
AB - Low circulating levels of vitamin D were associated with decreased muscle
strength and physical performance. Along this line, the present study was aimed
to investigate: i) the therapeutic potential of vitamin D in cancer-induced
muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in
tumor-bearing animals.Rats bearing the AH130 hepatoma showed decreased
circulating vitamin D compared to control rats, while muscle vitamin D receptor
(VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression
increased after vitamin D administration, without exerting appreciable effects on
body weight and muscle mass.The effects of vitamin D on muscle cells were studied
in C2C12 myocytes. Vitamin D-treated myoblasts did not differentiate properly,
fusing only partially and forming multinucleated structures with aberrant shape
and low myosin heavy chain content. Vitamin D treatment resulted in VDR
overexpression and myogenin down-regulation. Silencing VDR expression in C2C12
cultures abrogated the inhibition of differentiation exerted by vitamin D
treatment.These data suggest that VDR overexpression in tumor-bearing animals
contributes to muscle wasting by impairing muscle regenerative program. In this
regard, attention should be paid when considering vitamin D supplementation to
patients affected by chronic pathologies where muscle regeneration may be
involved.
PMID- 28423520
TI - Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor
infiltrating lymphocytes in testicular germ cell tumors.
AB - PURPOSE: Testicular germ cell tumors (TGCTs) are nearly universally curable
malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative
in a small subgroup of patients. Previously, we showed that PD-L1 overexpression
is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes
(TILs) are prognostic in different types of cancer. This study aimed to evaluate
the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. RESULTS: PD-L1
positive TILs were found significantly more often in seminomas (95.9% of
patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%),
choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with
high infiltration of PD-L1 positive TILs (HS >= 160) had significantly better
progression-free survival (HR = 0.17, 95% CI 0.09 - 0.31, p = 0.0006) and overall
survival (HR = 0.08, 95% CI 0.04 - 0.16, p = 0.001) opposite to patients with
lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in
TGCTs. MATERIALS AND METHODS: Surgical specimens from 240 patients with primary
TGCTs were included into this translational study. The PD-1 and PD-L1 expression
on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti
PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted
histoscore (HS) method. CONCLUSIONS: The prognostic value of PD-L1 expressing
TILs in TGCTs was demonstrated for the first time.
PMID- 28423521
TI - Therapeutic sensitivity to Rac GTPase inhibition requires consequential
suppression of mTORC1, AKT, and MEK signaling in breast cancer.
AB - Rac GTPases have oncogenic roles in cell growth, survival, and migration. We
tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell
lines. EHT1864-induced growth inhibition was associated with dual inhibition of
the PI3K/AKT/mTORC1 and MEK/ERK pathways. Breast cancer cells harboring PIK3CA
mutations or HER2 overexpression were most sensitive to Rac inhibition,
suggesting that such oncogenic alterations link Rac activation with
PI3K/AKT/mTORC1 and MEK/ERK signaling. Interestingly, EHT1864 decreased
activation of the mTORC1 substrate p70S6K earlier than AKT inhibition, suggesting
that Rac may activate mTORC1/p70S6K independently of AKT. Comparison of the
growth-inhibitory profile of EHT1864 to 137 other anti-cancer drugs across 656
cancer cell lines revealed significant correlation with the p70S6K inhibitor PF
4708671. We confirmed that Rac complexes contain MEK1/2 and ERK1/2, but also
contain p70S6K; these interactions were disrupted by EHT1864. Pharmacokinetic
profiles revealed that EHT1864 was present in mouse plasma at concentrations
effective in vitro for approximately 1 h after intraperitoneal administration.
EHT1864 suppressed growth of HER2+ tumors, and enhanced response to anti-estrogen
treatment in ER+ tumors. Further therapeutic development of Rac inhibitors for
HER2+ and PIK3CA-mutant cancers is warranted.
PMID- 28423522
TI - PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast.
AB - OBJECTIVE: Serine protease 3 (PRSS3) is an isoform of trypsinogen, and plays an
important role in the development of many malignancies. The objective of this
study was to determine PRSS3 mRNA and protein expression levels in invasive
ductal carcinoma of the breast and normal surrounding tissue samples. RESULTS:
Both PRSS3 mRNA and protein levels were significantly higher in invasive ductal
carcinoma of the breast tissues than in normal or benign tissues (all P < 0.05).
High PRSS3 protein levels were associated with patients' age, histological grade,
Her-2 expression level, ki-67 expression, and the 5.0-year survival rate. These
high protein levels are independent prognostic markers in invasive ductal
carcinoma of the breast. MATERIALS AND METHODS: We used real-time quantitative
polymerase chain reactions (N = 40) and tissue microarray immunohistochemistry
analysis (N = 286) to determine PRSS3 mRNA and protein expression, respectively.
PRSS3 protein levels in invasive ductal carcinoma of the breast tissues were
correlated with the clinical characteristics of patients with invasive ductal
carcinoma of the breast and their 5.0-year survival rate. CONCLUSIONS: PRSS3 acts
as an oncogene in invasive ductal carcinoma of the breast development and
progression. This finding implies that detection of PRSS3 expression can be a
useful prognosis marker and the targeting of PRSS3 can potentially represent a
new strategy for invasive ductal carcinoma of the breast treatment.
PMID- 28423523
TI - miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like
phenotype by activating Wnt/beta-catenin signalling.
AB - PURPOSE: To examine the role of miR-106b-5p in regulating the cancer stem-cell
like phenotype in clear cell renal cell carcinomas (ccRCC). EXPERIMENTAL DESIGN:
Real-time PCR was performed to evaluate miR-106b-5p levels in ccRCC cell lines
and patients specimens. A series of in vivo and in vitro assays were performed to
confirm the effect of miR-106b-5p on ccRCC stemness phenotype. RESULTS: ccRCC
cells and tissues expressed more miR-106b-5p than normal controls. Gain- and loss
of-function studies demonstrated that overexpression of miR-106b-5p in ccRCC
cells increased the spheres formation ability and the proportion of side
population cells. Ectopic expression of miR-106b-5p in ccRCC cells increased
tumour growth rates and the number of metastatic colonies in the lungs by using
an orthotopic kidney cancer model and a tail vein injection model, respectively.
Mechanistic studies revealed that, miR-106b-5p has an activating effect on
Wnt/beta-catenin signalling. miR-106p-5p overexpression simultaneously targets
multiple negative regulators of the Wnt/beta-catenin pathway, namely, LZTFL1,
SFRP1 and DKK2. In addition, we also confirmed that miR-106b-5p and its targets
expression correlates with the overall-survival of ccRCC patients from TCGA.
CONCLUSIONS: These findings suggest that miR-106b-5p mediates the constitutive
activation of Wnt/beta-catenin signalling, likely serving as a potential
therapeutic target for ccRCC.
PMID- 28423524
TI - Critically short telomeres and toxicity of chemotherapy in early breast cancer.
AB - Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy,
fatigue) compromises long-term administration. Preclinical data suggest that the
burden of critically short telomeres (< 3 kilobases, CSTs), but not average
telomere length by itself, accounts for limited tissue renewal and turnover
capacity. The impact of this parameter (which can be modified with different
therapies) in chemotherapy-derived toxicity has not been studied.Blood from 115
treatment-naive patients from a clinical trial in early HER2-negative breast
cancer that received weekly paclitaxel (80 mg/m2 for 12 weeks) either alone or in
combination with nintedanib and from 85 healthy controls was prospectively
obtained and individual CSTs and average telomere lenght were determined by HT Q
FISH (high-throughput quantitative FISH). Toxicity was graded according to NCI
common toxicity criteria for adverse events (NCI CTCAE V.4.0). The variable under
study was "number of toxic episodes" during the 12 weeks of therapy.The
percentage of CSTs ranged from 6.5%-49.4% and was directly associated with the
number of toxic events (R2 = 0.333; P < 0.001). According to a linear regression
model, each 18% increase in the percentage of CSTs was associated to one
additional toxic episode during the paclitaxel cycles; this effect was
independent of the age or treatment arm. Patients in the upper quartile (> 21.9%
CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019)
episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average
telomere length was unrelated to the incidence of side effects.The percentage of
CSTs, but not the average telomere size, is associated with weekly paclitaxel
derived toxicity.
PMID- 28423525
TI - The combination of circulating long noncoding RNAs AK001058, INHBA-AS1, MIR4435
2HG, and CEBPA-AS1 fragments in plasma serve as diagnostic markers for gastric
cancer.
AB - BACKGROUND: Suitable diagnostic markers for cancers are urgently required in
clinical practice. Long non-coding RNAs, which have been reported in many cancer
types, are a potential new class of biomarkers for tumor diagnosis. RESULTS: Five
lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were
validated to be increased in gastric cancer tissues. Furthermore, we found that
plasma level of these five lncRNAs were significantly higher in gastric cancer
patients compared with normal controls. By receiver operating characteristic
analysis, we found that the combination of plasma lncRNAs with the area under the
curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is
a better indicator of gastric cancer than their individual levels or other lncRNA
combinations. Simultaneously, we found that the expression levels of a series of
MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of
them higher than that in healthy control plasma samples. MATERIALS AND METHODS:
LncRNA gene expression profiles were analyzed in two pairs of human gastric
cancer and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer
associated lncRNAs were selected and assessed by quantitative real-time
polymerase chain reaction in gastric tissues, and 5 of them were further analyzed
in gastric cancer patients' plasma. CONCLUSIONS: Our results demonstrate that
certain lncRNAs, such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are
enriched in human gastric cancer tissues and significantly elevated in the plasma
of patients with gastric cancer. These findings indicate that the combination of
these four lncRNAs might be used as diagnostic or prognostic markers for gastric
cancer patients.
PMID- 28423526
TI - CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and
prognosis of Kazakh esophageal squamous cell carcinoma.
AB - M2 macrophages was domesticated by tumor microenvironment to produce some
angiogenic molecules and protease, facilitating angiogenesis and matrix
breakdown, promoting tumor invasive and metastasis. However, The function of M2
macrophages to progression of eophageal carcinoma, especially Kazakh esophageal
carcinoma is still dimness. This study aims to investigate M2 macrophages
correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and
the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163
and CD34 as the marker of M2 macrophages and endothelial cells, were used to
identify the M2 macrophages density and microvessel density, respectively.
Immunohistochemistry staining was evaluated the expression of MMP9. The number of
infiltrated CD163-positive M2 macrophages in tumor islets and stroma was
significantly higher than in cancer adjacent normal tissues. The increased of M2
macrophages and microvessel density were significantly correlated with more
malignant phenotypes including lymph node metastasis and clinical stage
progression. Meanwhile, the expression of MMP9 showed much higher level in
esophageal squamous cell carcinoma than that in cancer adjacent normal tissues,
and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was
significantly associated with age, depth of tumor invasion, lymph node
metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor
stroma was positively associated with microvessel density and the expression of
MMP9, and as an independent poorly prognostic factor for overall survival time of
Kazakh esophageal squamous cell carcinoma. These findings suggest the increased
number of M2 macrophages correlated with high expression of MMP9 and high
microvessel density may contribute to the tumor aggressiveness and angiogenesis,
promoting the progression of Kazakh esophageal squamous cell carcinoma.
PMID- 28423527
TI - HES1 promotes extracellular matrix protein expression and inhibits proliferation
and migration in human trabecular meshwork cells under oxidative stress.
AB - Glaucoma is the leading cause of irreversible blindness. The most prevalent form
of glaucoma is primary open-angle glaucoma (POAG). Oxidative stress is one of the
major pathogenic factors of the POAG, and can elicit molecular and functional
changes in trabecular meshwork cells, causing increased aqueous humor outflow
resistance and elevated intraocular pressure. However, the regulatory mechanisms
underlying oxidative stress-induced cell phenotypic changes remain elusive.
Herein, we exposed primary human trabecular meshwork cells to the oxidative
stress induced by 300 MUM H2O2 for 2 h, and found significantly up-regulated
expression of extracellular matrix proteins and a transcription factor, hairy and
enhancer of split-1 (HES1). The cell functions, including migration and
proliferation, were impaired by the oxidative stress. Furthermore, HES1 shRNA
abrogated the extracellular matrix protein up-regulation and rescued the
functional defects caused by the oxidative stress; conversely, HES1
overexpression resulted in the molecular and functional changes similar to those
induced by H2O2. These results suggest that HES1 promotes extracellular matrix
protein expression and inhibits proliferative and migratory functions in the
trabecular meshwork cells under oxidative stress, thereby providing a novel
pathogenic mechanism underlying and a potential therapeutic target to the POAG.
PMID- 28423528
TI - Level of FACT defines the transcriptional landscape and aggressive phenotype of
breast cancer cells.
AB - Although breast cancer (BrCa) may be detected at an early stage, there is a
shortage of markers that predict tumor aggressiveness and a lack of targeted
therapies. Histone chaperone FACT, expressed in a limited number of normal cells,
is overexpressed in different types of cancer, including BrCa. Recently, we found
that FACT expression in BrCa correlates with markers of aggressive BrCa, which
prompted us to explore the consequences of FACT inhibition in BrCa cells with
varying levels of FACT.FACT inhibition using a small molecule or shRNA caused
reduced growth and viability of all BrCa cells tested. Phenotypic changes were
more severe in "high- FACT" cells (death or growth arrest) than in "low-FACT"
cells (decreased proliferation). Though inhibition had no effect on the rate of
general transcription, expression of individual genes was changed in a cell
specific manner. Initially distinct transcriptional profiles of BrCa cells became
similar upon equalizing FACT expression. In "high-FACT" cells, FACT supports
expression of genes involved in the regulation of cell cycle, DNA replication,
maintenance of an undifferentiated cell state and regulated by the activity of
several proto-oncogenes. In "low-FACT" cells, the presence of FACT reduces
expression of genes encoding enzymes of steroid metabolism that are
characteristic of differentiated mammary epithelia.Thus, we propose that FACT is
both a marker and a target of aggressive BrCa cells, whose inhibition results in
the death of BrCa or convertion of them to a less aggressive subtype.
PMID- 28423529
TI - PIF* promotes brain re-myelination locally while regulating systemic inflammation
clinically relevant multiple sclerosis M.smegmatis model.
AB - Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis
(MS) is a demyelinating autoimmune disease with few clinical forms and uncertain
etiology. Current studies suggest that it is likely caused by infection(s)
triggering a systemic immune response resulting in antigen/non-antigen-related
autoimmune response in central nervous system (CNS). New therapeutic approaches
are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a
local and systemic immunity regulatory role. Synthetic PIF (PIF) duplicates
endogenous peptide's protective effect in pre-clinical autoimmune and
transplantation models. PIF protects against brain hypoxia-ischemia by directly
targeting microglia and neurons. In chronic experimental autoimmune encephalitis
(EAE) model PIF reverses paralysis while promoting neural repair. Herein we
report that PIF directly promotes brain re-myelination and reverses paralysis in
relapsing remitting EAE MS model. PIF crosses the blood-brain barrier targeting
microglia. Systemically, PIF decreases pro-inflammatory IL23/IL17 cytokines,
while preserving CNS-specific T-cell repertoire. Global brain gene analysis
revealed that PIF regulates critical Na+/K+/Ca++ ions, amino acid and glucose
transport genes expression. Further, PIF modulates oxidative stress, DNA
methylation, cell cycle regulation, and protein ubiquitination while regulating
multiple genes. In cultured astrocytes, PIF promotes BDNF-myelin synthesis
promoter and SLC2A1 (glucose transport) while reducing deleterious E2F5, and
HSP90ab1 (oxidative stress) genes expression. In cultured microglia, PIF
increases anti-inflammatory IL10 while reducing pro-inflammatory IFNgamma
expression. Collectively, PIF promotes brain re-myelination and neuroprotection
in relapsing remitting EAE MS model. Coupled with ongoing, Fast-Track FDA
approved clinical trial, NCT#02239562 (immune disorder), current data supports
PIF's translation for neurodegenerative disorders therapy.
PMID- 28423530
TI - Patterns of failure and clinical outcomes of definitive radiotherapy for cervical
esophageal cancer.
AB - PURPOSE: Because of the scarcity of cervical esophageal cancer (CEC), data for
this disease entity is limited. We aim to evaluate the outcomes, prognostic
factors and failure patterns of CEC treated by contemporary radiotherapy (RT).
METHODS: We retrospectively analyzed 86 CEC patients consecutively treated
between 2007 and 2015 by definitive RT with or without concurrent chemotherapy.
RT was mainly delivered with Intensity Modulated Irradiation Therapy (IMRT) or
Volumetric-Modulated Arc Therapy (VMAT). Statistical analyses were performed on
survival, prognostic factors and failure patterns. RESULTS: The median follow-up
time was 19.4 months. The 3-year overall survival (OS), local regional failure
free survival (LRFFS), distant metastatic free survival (DMFS), and progression
free survival (PFS) were 53.6%, 57.9%, 81.5% and 41.5%, respectively. Independent
predictors for poorer OS were N stage, hoarseness and recurrent laryngeal nerve
lymph node (RLN) involvement, and predictors for LRFFS were N stage and EQD2
(equivalent dose in 2 Gy fraction) to gross tumor volume (GTV), with >= 66Gy
achieving local control of 94.7%. Patients receiving elective nodal irradiation
(ENI) had better nodal regional control than those receiving involved field
irradiation (IFI). 31 (36%) patients had treatment failure and 15 (17.4%), 8
(9.3%) and 14 (16.2%) patients had local, regional, and distant failure,
respectively. 86.7% (13/15) local failures were within GTV, and supraclavicular
region (62.5%, 5/8) was the most common regional failure site. No severe
toxicities were observed. CONCLUSIONS: Our results seem to indicate that good
locoregional control might be achieved for CEC with adequate radiation dose and
treatment planning approaches.
PMID- 28423531
TI - Epigenetic inactivation of HOXA11, a novel functional tumor suppressor for renal
cell carcinoma, is associated with RCC TNM classification.
AB - Epigenetic inactivation of HOXA11, a putative tumor suppressor, is frequently
observed in a number of solid tumors, but has not been described in RCC (renal
cell carcinoma). In this study, we investigated the expression, epigenetic
changes and the function of HOXA11 in human renal cell carcinoma (RCC). HOXA11
was silenced or down-regulated in RCC cell lines and tissues. Methylation
specific PCR (MSP) and bisulfite genomic sequencing (BGS) revealed that the
HOXA11 promoter was hypermethylated in 5/6 RCC cell lines. Demethylation
treatment resulted in demethylation of the promoter and increased HOXA11
expression in these cell lines. HOXA11 methylation was also detected in 68/95
(70.5%) primary RCC tumors, but only rare adjacent non-malignant renal tissues
(13%, 3/23) showed hypermethylation of promoter. We also found that the
methylation of HOXA11 was associated with higher TNM classification of RCC
(p<0.05). Ectopic expression of HOXA11 led to significant inhibition of
proliferation, colony formation, migration and invasion abilities and induced RCC
cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling. Thus, our
study demonstrated that HOXA11 function as a tumor suppressor in RCC, while it is
frequently silenced by promoter methylation in RCC.
PMID- 28423532
TI - Implication of vascular endothelial growth factor A and C in revealing diagnostic
lymphangiogenic markers in node-positive bladder cancer.
AB - Several lymphangiogenic factors, such as vascular endothelial growth factors
(VEGFs), have been found to drive the development of lymphatic metastasis in
bladder cancer (BCa).Here, we have analyzed the gene expression of
lymphangiogenic factors in tissue specimens from 12 non-muscle invasive bladder
cancers (NMIBC) and 11 muscle invasive bladder cancers (MIBC), considering tumor
and tumor-adjacent normal bladder areas obtained from the same organs. We then
compared the results observed in patients with those obtained after treating
human primary bladder microvascular endothelial cells (MEC) with either direct
stimulation with VEGF-A or VEGF-C or by co-culturing (trans-well assay) MEC with
bladder cancer cell lines varying in VEGF-A and VEGF-C production based on tumor
grade.The genes of three markers of lymphatic endothelial commitment and
development (PDPN, LYVE-1 and SLP-76) were significantly overexpressed in tissues
of MIBC patients showing positive lymphovascular invasion (LVI+), lymph node
metastasis (Ln+) and tumor progression. Their expression was also significantly
enhanced either after direct stimulation of MEC by VEGF-A and VEGF-C or in the
trans-well assay with each bladder cancer cell line.SLP-76 showed the highest
gene expression. Both VEGF-A and VEGF-C also enhanced the expression of SLP-76
protein in MEC. However, a correlation between increase of SLP-76 gene expression
and the ability of MEC to migrate could only be seen after induction by VEGF
C.The significant expression of SLP-76 in LVI+/Ln+ progressive MIBC and its
overexpression in MEC after VEGF-A and VEGF-C stimulation suggest the need to
develop this regulator of developmental lymphangiogenesis as a diagnostic tool in
BCa.
PMID- 28423533
TI - SPC24 is critical for anaplastic thyroid cancer progression.
AB - In the past 2 decades, the incidence of thyroid cancer has been rapidly
increasing worldwide. Anaplastic thyroid cancer (ATC) is the most lethal of all
thyroid cancers and one of the most aggressive human carcinomas. SPC24 is an
important component of the mitotic checkpoint machinery in the tumorigenesis and
high levels of SPC24 have been found in colorectal and hepatocellular carcinomas,
but its role in anaplastic thyroid cancer is still unclear. Our results showed
that SPC24 was high expressed in human thyroid cancer samples. In addition,
knockingdown endogenous SPC24 could repress cell growth, inhibit cell invasive
ability and promote apoptosis in different ATC cells. Next, in vivo xenograft
studies indicated that the SPC24 knockdown cells has decreased tumor size
compared to the controls. This conclusion is also endorsed by our studies using
human thyroid cancer samples. Taken together, our data demonstrates that SPC24
can serve as a promising prognostic biomarker of ATC cells and it is a novel
strategy which could be developed by targeting SPC24 in future.
PMID- 28423534
TI - Estrogen deficiency is associated with hippocampal morphological remodeling of
early postmenopausal mice.
AB - Estrogen (E2) deficiency is reported to involve in the impairment of cognition in
postmenopausal women. However, the morphological basis is still unclear. In the
present study, using transmission electron microscopy (TEM), we observed the
ultrastructure of hippocampus in female C57BL/6 mice at the age of 18 months (18
M) which is considered as the early stage of postmenopause (n = 8). Compared with
control mice aged 6 M (n = 8), we identified that the morphological changes in
the hippocampus of these menopausal mice were mitochondrial damage, lipofuscin
deposition and microtubule degradation. Notably, after E2 was subcutaneously
injected into mice aged 16 M with a dosage of 3.5 MUg/kg every three days for two
months in the 18 M + E2 group (n = 8), mitochondrial damage and lipofuscin
deposition in the DG region of hippocampus were prevented, but the degraded
microtubules in the hippocampus of postmenopausal mice were failed to restore.
These data suggest that hippocampal ultrastructure remodeling in mice can be
initiated at the early stage of postmenopause, E2 supplementation could only have
an effect on mitochondrial damage and lipofuscin increase.
PMID- 28423535
TI - Overall survival with crizotinib and next-generation ALK inhibitors in ALK
positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide
cohort retrospective study.
AB - Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi)
crizotinib in a large population of unselected patients with ALK-positive non
small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with
crizotinib in unselected ALK-positive NSCLC patients and whether post-progression
systemic treatments affect survival outcomes.ALK-positive NSCLC patients
receiving crizotinib in French expanded access programs or as approved drug were
enrolled. We collected clinical and survival data, RECIST-defined progressive
disease (PD) and post-PD systemic treatment efficacy. We performed multivariable
analysis of OS from crizotinib initiation and PD under crizotinib.At time of
analysis, 209 (65.7%) of the 318 included patients had died. Median OS with
crizotinib was 16.6 months. The line of crizotinib therapy did not impact
survival outcomes. Of the 263 patients with PD, 105 received best supportive
care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation
ALKi. Next-generation ALKi treatment correlated with better survival outcomes in
multivariate analysis. These patients had a median post-PD survival of 25.0
months and median OS from metastatic disease diagnosis of 89.6 months.Unselected
ALK-positive NSCLC patients achieve good survival outcomes with crizotinib
therapy. Next-generation ALKi may provide survival improvement after PD under
crizotinib.
PMID- 28423536
TI - JMJD3 suppresses stem cell-like characteristics in breast cancer cells by
downregulation of Oct4 independently of its demethylase activity.
AB - Epigenetic regulator JMJD3 plays an important role in both tumor progression and
somatic cell reprogramming. Here, we explored the effect of JMJD3 on the stem
cell-like characteristics of breast cancer and its underlying mechanism involving
stemness-related transcription factor Oct4. Our data revealed that, in breast
cancer cells lines and an orthotopic xenograph mouse model of breast cancer,
ectopic overexpression of JMJD3 suppressed stem cell-like characteristics of
breast cancer cells, whereas knockdown of JMJD3 promoted these characteristics.
Oct4 mediated the suppressive effects of JMJD3 on the stemness of breast cancer
cells. The inhibitory effect of JMJD3 on Oct4 was independent of demethylase
activity, but mediated via degradation of PHF20. Furthermore, we applied an
agonist of the vitamin D receptor, paricalcitol, and found that it induced JMJD3
in breast cancer cells. Our data showed that administration of paricalcitol
suppressed stem cell-like characteristics and Oct4 expression. Taken together,
JMJD3 inhibits the stem cell-like characteristics in breast cancer by suppression
of stemness factor Oct4 in a PHF20-dependent manner. Administration of
paricalcitol leads to upregulation of JMJD3 that suppresses Oct4 expression and
the stem cell-like characteristics in breast cancer.
PMID- 28423537
TI - Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with
Ki67 in estrogen receptor-positive HER2-negative breast cancer.
AB - PAM50/Prosigna gene expression-based assay identifies three categorical risk of
relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal
patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative
(HER2-) early breast cancer. Low risk patients might not need adjuvant
chemotherapy since their risk of distant relapse at 10-years is below 10% with
endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2-
and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A
tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however,
the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0
10% group was 42.7% (with tumor sizes <=2 cm) and 33.9% (with tumor sizes > 2
cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or
ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low
risk outcome patients or Luminal A disease in the clinical setting is unreliable.
In the absence of a well-validated prognostic gene expression-based assay, the
optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A
disease remains at 14%.
PMID- 28423538
TI - Gene regulatory pattern analysis reveals essential role of core transcriptional
factors' activation in triple-negative breast cancer.
AB - BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer
subtype. Genome-scale molecular characteristics and regulatory mechanisms that
distinguish TNBC from other subtypes remain incompletely characterized. RESULTS:
By combining gene expression analysis and PANDA network, we defined three
different TF regulatory patterns. A core TNBC-Specific TF Activation Driven
Pattern (TNBCac) was specifically identified in TNBC by computational analysis.
The essentialness of core TFs (ZEB1, MZF1, SOX10) in TNBC was highlighted and
validated by cell proliferation analysis. Furthermore, 13 out of 35 co-targeted
genes were also validated to be targeted by ZEB1, MZF1 and SOX10 in TNBC cell
lines by real-time quantitative PCR. In three breast cancer cohorts, non-TNBC
patients could be stratified into two subgroups by the 35 co-targeted genes along
with 5 TFs, and the subgroup that more resembled TNBC had a worse prognosis.
METHODS: We constructed gene regulatory networks in breast cancer by Passing
Attributes between Networks for Data Assimilation (PANDA). Co-regulatory modules
were specifically identified in TNBC by computational analysis, while the
essentialness of core translational factors (TF) in TNBC was highlighted and
validated by in vitro experiments. Prognostic effects of different factors were
measured by Log-rank test and displayed by Kaplan-Meier plots. CONCLUSIONS: We
identified a core co-regulatory module specifically existing in TNBC, which
enabled subtype re-classification and provided a biologically feasible view of
breast cancer.
PMID- 28423539
TI - Interplay between DeltaNp63 and miR-138-5p regulates growth, metastasis and
stemness of oral squamous cell carcinoma.
AB - TP63 acts as a master regulator in epithelia development and in the progression
of various cancers, but its role in oral cancer pathogenesis remains unknown.
This study aimed to explore the role of TP63 in the progression of oral squamous
cell carcinoma (OSCC). This study shows that DeltaNp63, the predominant isoform
of TP63, is significantly upregulated in OSCC tissues and cell lines compared
with their normal counterparts, and its expression is closely correlated with
pathological differentiation, lymph node metastasis and clinical stage in
patients with OSCC. The overexpression of DeltaNp63 promotes growth, metastasis
and stem-like properties in OSCC cells, and DeltaNp63 depletion significantly
represses OSCC cellular phenotypes in vitro and in vivo. The DeltaNp63 isoform
transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p
expression partially abolishes the effect of upregulating DeltaNp63. This study
also demonstrates that miR-138-5p directly targets DeltaNp63, resulting in
crosstalk with DeltaNp63. The correlation between DeltaNp63 and miR-138-5p was
further validated in OSCC tissues and was found to be significantly associated
with the prognosis of patients with OSCC. Therefore, our data reveal that the
interplay between DeltaNp63 and miR-138-5p promotes OSCC progression by
regulating cell growth, metastasis and stemness.
PMID- 28423540
TI - Correlations between intravoxel incoherent motion (IVIM) parameters and
histological findings in rectal cancer: preliminary results.
AB - Our purpose was to correlate different intravoxel incoherent motion (IVIM),
histopathological and clinical parameters in rectal cancer. 17 patients with
histologically proven rectal cancer investigated on a 3.T device were included
into the study. DWI was performed using a multi-slice single-shot echo-planar
imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm.2 A polygonal
region of interest was drawn within the tumors on every b image. The following
parameters were retrieved from IVIM: apparent diffusion coefficient (ADC), true
diffusion (D), pseudo diffusion coefficient (D*), perfusion factor (f), and
relative perfusion f.D*. In every case, cell count, nucleic areas, proliferation
index KI 67, and microvessel density were estimated on histopathological
specimens. Pearson's correlation coefficient was used to analyze the association
between the parameters. ADC correlated well with KI 67 index and D tended to
correlate with cell count and KI 67. ADC and D tended to correlate with total
nucleic area. The perfusion factor f correlated well with stained vessel area,
total vessel area, and vessel count. D* and fD* correlated with mean vessel
diameter. Distant metastasized tumors had higher D* and fD* values. IVIM
parameter reflected different clinical and histopathological features in rectal
cancer.
PMID- 28423541
TI - RNA sequencing analysis reveals protective role of kruppel-like factor 3 in
colorectal cancer.
AB - The Kruppel-like factor (KLF) family of transcription factors plays an important
role in embryonic formation and cancer progression. This study was performed to
determine the clinical importance of the KLF family in colorectal cancer (CRC).
In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were
used to comprehensively study the role of the KLF family in CRC. The results were
then further validated using an in-house cohort (n=194). Univariate and
multivariate Cox proportional hazards models were used to assess the risk factors
for survival. In the TCGA cohort, KLF3 (hazard ratio [HR], 0.501; 95% confidence
interval [CI], 0.272-0.920; P=0.025), KLF14 (HR, 1.454; 95% CI, 1.059-1.995;
P=0.020), and KLF17 (HR, 1.241; 95% CI, 1.030-1.494, P=0.023) were identified as
potential biomarkers in the univariate analysis, but after Cox proportional
hazards analysis, only KLF3 (HR, 0.473; 95% CI, 0.230-0.831; P=0.012) was shown
to be independently predictive of overall survival in patients with CRC. This
finding was validated in our in-house cohort, which demonstrated that KLF3
expression was an independent predictor of both overall survival (HR, 0.628; 95%
CI, 0.342-0.922; P=0.035) and disease-free survival (HR, 0.421; 95% CI, 0.317
0.697, P=0.016). KLF3 expression was inversely correlated with the N stage
(P=0.015) and lymphovascular invasion (P=0.020). Collectively, loss of KLF3 was
correlated with aggressive phenotypes and poor survival outcomes. KLF3 might be a
potential new predictor and therapeutic target for CRC. Further study is needed
for a more detailed understanding of the role of KLF3 in CRC.
PMID- 28423542
TI - DNA methylation intratumor heterogeneity in localized lung adenocarcinomas.
AB - Cancers are composed of cells with distinct molecular and phenotypic features
within a given tumor, a phenomenon termed intratumor heterogeneity (ITH).
Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas;
however, the nature of methylation ITH in lung cancers has not been well
investigated. In this study, we generated methylation profiles of 48 spatially
separated tumor regions from 11 localized lung adenocarcinomas and their matched
normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip
array. We observed methylation ITH within the same tumors, but to a much less
extent compared to inter-individual heterogeneity. On average, 25% of all
differentially methylated probes compared to matched normal lung tissues were
shared by all regions from the same tumors. This is in contrast to somatic
mutations, of which approximately 77% were shared events amongst all regions of
individual tumors, suggesting that while the majority of somatic mutations were
early clonal events, the tumor-specific DNA methylation might be associated with
later branched evolution of these 11 tumors. Furthermore, our data showed that a
higher extent of DNA methylation ITH was associated with larger tumor size
(average Euclidean distance of 35.64 (> 3cm, median size) versus 27.24 (<= 3cm),
p = 0.014), advanced age (average Euclidean distance of 34.95 (above 65) verse
28.06 (below 65), p = 0.046) and increased risk of postsurgical recurrence
(average Euclidean distance of 35.65 (relapsed patients) versus 29.03 (patients
without relapsed), p = 0.039).
PMID- 28423543
TI - MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down
regulating the expression of MCL-1.
AB - Cancer stem cells are considered as the cell population which is responsible for
chemoresistance and treatment failure in breast cancer patients. Therefore, it is
urgent to explore the mechanism by which cancer stem cells survive under the
treatment of chemotherapeutic drugs such as cisplatin. In this paper, we
demonstrated significant decrease of miR-519d in breast cancer stem cells by
quantitative RT-PCR analysis. Furthermore, we found the enforced expression of
miR-519d in T-47D-cancer stem cells significantly increased their sensitivity to
cisplatin through the apoptosis pathway. In addition, the gene of MCL-1, which is
a member of pro-apoptotic Bcl-2 family, was found to be the target of miR-519d in
T-47D-cancer stem cells. Our date demonstrated that enforced miR-519d expression
enhanced the cisplatin-induced apoptosis through the MCL-1 dependent mitochondria
pathway in breast cancer stem cells. Taken together, the present study suggests
that miR-519d reduces chemoresistance in breast cancer stem cells, and
understanding of miR-519d may be helpful for increasing the efficacy of
chemotherapy.
PMID- 28423544
TI - Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx
assay: better prognostic indicator than Hans algorithm.
AB - Diffuse large B-cell lymphomas (DLBCLs) are clinically heterogeneous and need a
biomarker that can predict the outcome of treatments accurately. To assess the
prognostic significance of the cell-of-origin type for DLBCLs, we applied the
Lymph2Cx assay using a NanoString gene expression platform on formalin-fixed
paraffin wax-embedded pretreatment tissues obtained from 82 patients with de novo
DLBCL, not otherwise specified. All patients were treated with rituximab plus
cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first
line of chemotherapy. Based on the expression levels of Bcl-6, CD10, and MUM-1
measured by immunohistochemistry, cases were subdivided into germinal center B
cell (GCB) and non-GCB types according to the Hans algorithm. NanoString assay
was performed on 82 cases. The Lymph2Cx assay successfully classified 82 cases
into three categories: activated B-cell (ABC), GCB, and unclassified types. The
concordance rate between the Lymph2Cx assay and the Hans algorithm was 73.6%. The
Lymph2Cx-defined ABC type had significantly poorer outcomes compared with the GCB
type (5-year overall survival, GCB vs. ABC, 96.6% vs. 77.1%, P = 0.020; 5-year
disease-free survival, GCB vs. ABC, 96.6% vs. 79.2%, P = 0.018). In contrast, no
significant differences were observed in survival between the two patient
subgroups with DLBCL types classified by the Hans algorithm. The Lymph2Cx assay
is a robust, reliable method for predicting the outcome of patients with DLBCL
treated with R-CHOP chemotherapy.
PMID- 28423545
TI - Hobnail variant of papillary thyroid carcinoma: molecular profiling and
comparison to classical papillary thyroid carcinoma, poorly differentiated
thyroid carcinoma and anaplastic thyroid carcinoma.
AB - BACKGROUND: As a rare but aggressive papillary thyroid carcinoma (PTC) variant,
the genetic changes of hobnail variant of PTC (HVPTC) are still unclear. RESULTS:
The prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort.
73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were
successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven
mutation variant types were identified among 11 genes. BRAF V600E mutation was
the most common mutation, which is present in almost all HVPTC samples (16/17,
94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT
promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and
TP53 mutation are almost exclusively present among ATC and PDTC samples although
TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations
were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The
only patient who died of disease progression harbored concomitant TERT C228T
mutation, BRAF V600E mutation and TP53 mutation. METHODS: HVPTC cases were
identified from a group of 1062 consecutive surgical specimens diagnosed as PTC
between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to
investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC),
poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma
(ATC). CONCLUSION: As an aggressive variant of PTC, HVPTC has relatively specific
molecular features, which is somewhat different from both CPTC and ATC/PDTC and
may underlie its relatively aggressive behavior.
PMID- 28423546
TI - Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of
colorectal cancer.
AB - Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human
colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided
significant efficiency for immunotherapy in CRC pre-clinical models. We therefore
evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2.
Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was
restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with
111In or 177Lu with radiochemical purities >95%, specific activity ranging from
300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of
[111In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a
high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3;
SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific
absorbed dose calculations for [177Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing
the feasibility of using radioimmunotherapy of CRC with this radiolabeled
antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice
treated with [177Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo
experiments revealed specific DNA double strand breaks associated with cell
apoptosis in [177Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we
provide a proof-of-concept for the use of [111In/177Lu]DOTA-Ts29.2 that
specifically target in vivo aggressive TSPAN8-positive cells in CRC.
PMID- 28423547
TI - Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian
tumors: implications for HMGA2 expression.
AB - The High-mobility group AT-hook 2 protein (HMGA2) is involved in different
processes during tumorigenesis. High expression levels of HMGA2 are found in
various types of cancer, with recent studies highlighting the important role of
miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian
tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas)
analyzed for HMGA2 expression as well as the expression of two miRNAs targeting
this gene, let-7a and miR-30c. We also evaluated the expression of the fragile
histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to
be an enhancer of miR-30c expression and a repressor of let-7a, respectively.
HMGA2 was found expressed at high levels in most samples analyzed, with clear
cell carcinomas as the only exception. let-7a and miR-30c were highly deregulated
in all tumor types. LIN28A and FHIT were found overexpressed in all examined
tumor types. The chromosomal imbalances that might lead to loss of the genes
expressing let-7a and miR-30c could be evaluated on the basis of previously
generated karyotypic and high resolution comparative genomic hybridization (CGH)
data on 103 tumors. 76% of the samples with an imbalanced genome had at least one
chromosomal aberration leading to a deletion of a miRNA cluster for let-7a and
miR-30c. FISH using locus specific probes for these clusters validate the
aberrations at the gene level. Our study shows that genomic imbalances are
involved in miR-30c and let-7a deregulation. One can reasonably assume that
dysregulation of these miRNAs is a cause leading to HMGA2 upregulation in ovarian
tumors.
PMID- 28423548
TI - Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma.
AB - Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers.
LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D
binding to herpesvirus entry mediator on T cells) is a ligand that induces robust
anti-tumor immunity by enhancing the recruitment and activation of effector
immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T
lymphoma cells that stably overexpressed Axl also showed high expression of
LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT
expression was upregulated through activation of the PI3K/AKT signaling pathway
and transcriptional induction by Sp1. The lytic activity of cytotoxic T
lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition,
tumor volume and growth were markedly reduced due to enhanced apoptotic cell
death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed
upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral
infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl
bearing mice as compared to mock controls. These data strongly suggested that Axl
exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the
tumor microenvironment of T lymphoma.
PMID- 28423549
TI - HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde
trafficking route and forces cells to enter apoptosis.
AB - Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody
as a targeting module and fragment of Pseudomonas exotoxin A as an effector
(toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer
cells overexpressing HER2 receptor in vitro and on HER2-positive experimental
tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of
particular importance in the case of targeted therapeutic agent aimed at
personalizing treatment of disease in relation to molecular genetic
characteristics of each patient. After specific binding to HER2 on the cell
surface and clathrin-mediated endocytosis the immunotoxin passes through
retrograde trafficking route. During this route the immunotoxin molecule is
supposed to undergo enzymatic processing that ends in separation of C-terminal
and N-terminal fragments of the immunotoxin. Finally, C-terminal functionally
active fragment of 4D5scFv-PE40 arrests protein synthesis in cytoplasm followed
by cell death via apoptosis.
PMID- 28423550
TI - Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins
in platelet-derived growth factor b signaling pathway.
AB - Gastric cancer is one of the most common cancers in Asian countries. Searching
for reliable biomarkers involving the development of gastric cancer is important
for clinical practice. Quantitative proteomics has become an important method
contributed to the discovery of novel diagnostic or therapeutic targets for the
management of cancer. Here, we identified differently expressed proteins in
gastric cancer and normal gastric tissues by using the high resolution mass
spectrometer. Among the total of 2280 identified proteins, 87 were differentially
expressed between gastric cancer and normal gastric tissues. Notably, several
significant proteins are in the PDGF-B signaling pathway, including
peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which
were validated by western blot. Furthermore, upstream regulators including PDGF
B, PDGFR-beta, Akt, eIF4E and p70s6K were found significantly increased in the
gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the
proliferation of gastric cancer cells in vitro. The administration of exogenous
PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B
knockdown cells. Taken together, our findings suggested that PDGF-B signaling
pathway plays an important role in the regulation of gastric cancer proliferation
and the inhibition of this pathway may be a potential approach for treatment of
gastric cancer.
PMID- 28423551
TI - Metabolic reprogramming of the premalignant colonic mucosa is an early event in
carcinogenesis.
AB - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related
mortality in the United States. There is an increasing need for the
identification of biomarkers of pre-malignant and early stage CRC to improve risk
stratification and screening recommendations. In this study, we investigated the
possibility of metabolic and mitochondrial reprogramming early in the pre
malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients
undergoing screening colonoscopy, and gene expression of metabolic and
mitochondrial markers were assessed using real time quantitative PCR. Validation
studies were performed in two different animal models of colon carcinogenesis:
Pirc rats and AOM-treated rats. RESULTS: We found evidence of a Warburg effect in
the normal-appearing rectal mucosa of patients harboring precancerous lesions
elsewhere in the colon compared to control patients, with a significant increase
in HIF1alpha, SLC2A1 (referred to as GLUT1), PKM2, and LDHA. We also found
evidence of early mitochondrial changes in the colorectal field of patients
harboring pre-cancerous lesions, with significantly increased mitochondrial gene
expression of DRP1 (fission), OPA1 (fusion), PGC1-alpha (biogenesis), UCP2
(uncoupling) and mtND1 (copy number). Similar results were observed in the two
different animal models. CONCLUSIONS: These results demonstrate for the first
time evidence of early Warburg-like metabolic changes as well as changes in
mitochondrial function, dynamics and mtDNA copy number in endoscopically normal
premalignant colorectal mucosal field. These findings provide an opportunity for
the development of metabolic biomarkers that could be used for improving
screening recommendations and risk-stratification. This also provides a potential
target for novel chemopreventive strategies in the pre-malignant colorectal
field.
PMID- 28423552
TI - Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with
avelumab, an anti-PD-L1 antibody.
AB - The combined therapeutic potential of an immunocytokine designed to deliver IL-12
to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts
the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple
murine tumor models. The murine version of the immunocytokine, NHS-muIL12,
consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with
two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA,
NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer
plasma half-life and better antitumor efficacy against murine tumors than
recombinant murine IL-12. It is shown here that NHS-muIL12, in an IFN
gammaa??dependent mechanism, upregulates mPD-L1 expression on mouse tumors, which
could be construed as an immunosuppressive action. Yet concurrent therapy with
NHS-muIL12 and an anti-PD-L1 antibody resulted in additive/synergistic antitumor
effects in PD-L1a??expressing subcutaneously transplanted tumors (MC38, MB49) and
in an intravesical bladder tumor model (MB49). Antitumor efficacy correlated with
(a) with a higher frequency of tumor antigen-specific splenic CD8+ T cells and
(b) enhanced T cell activation over a wide range of NHS-muIL12 concentrations.
These findings suggest that combining NHS-muIL12 and an anti-PD-L1 antibody
enhances T cell activation and T cell effector functions within the tumor
microenvironment, significantly improving overall tumor regression. These results
should provide the rationale to examine the combination of these agents in
clinical studies.
PMID- 28423554
TI - uPAR directed-imaging of head-and-neck cancer.
PMID- 28423553
TI - Low vitamin D status is associated with inflammation in patients with prostate
cancer.
AB - Vitamin D deficiency has been associated with increased risks of prostate cancer.
Nevertheless, the mechanisms remain unclear. The aim of this study was to analyze
the association among prostate cancer, vitamin D status and inflammation. Sixty
patients with newly diagnosed prostate cancer and 120 age-matched controls were
recruited for this study. Vitamin D status was evaluated and serum inflammatory
molecules were measured. Serum 25-(OH)D was lower in patients with prostate
cancer. Moreover, serum 25(OH)D was lower in patients with severe prostate cancer
than patients with mild and moderate prostate cancer. By contrast, serum C
reactive protein (CRP) and interleukin (IL)-8, two inflammatory molecules, were
elevated in patients with prostate cancer. Serum 25-(OH)D was negatively
correlated with serum CRP and IL-8 in patients with prostate cancer. Additional
analysis showed that the percentage of vitamin D receptor positive nucleus in the
prostate was reduced in patients with prostate cancer. By contrast, the
percentage of nuclear factor kappa B p65-positive nucleus was elevated in
patients with prostate cancer. Our results provide evidence that there is an
association among prostate cancer, vitamin D deficiency and inflammatory
signaling. Inflammation may be an important mediator for prostate cancer
progression in patients with low vitamin D status.
PMID- 28423555
TI - HSP90 proteins in the scenario of tumor complexity.
PMID- 28423556
TI - Unwanted acquired mutations in Ba/F3 transformation assays.
PMID- 28423557
TI - Correction: Protective role of p53 in skin cancer: Carcinogenesis studies in mice
lacking epidermal p53.
PMID- 28423558
TI - Biological basis and clinical study of glycogen synthase kinase- 3beta-targeted
therapy by drug repositioning for glioblastoma.
AB - BACKGROUND: Glycogen synthase kinase (GSK)-3beta has emerged as an appealing
therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic
effect of the current approved drugs against GBM via inhibition of GSK3beta
activity both, in experimental setting and in a clinical study for recurrent GBM
patients by repositioning existent drugs in combination with temozolomide (TMZ).
MATERIALS AND METHODS: Progression-free and overall survival rates were compared
between patients with low or high expression of active GSK3beta in the primary
tumor. GBM cells and a mouse model were examined for the effects of GSK3beta
inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and
efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ
were tested in the mouse model and in a clinical study for recurrent GBM
patients. RESULTS: Activation of GSK3beta in the tumor inversely correlated with
patient survival as an independent prognostic factor. CLOVA cocktail
significantly inhibited cell invasion and proliferation. The patients treated
with CLOVA cocktail in combination with TMZ showed increased survival compared to
the control group treated with TMZ alone. CONCLUSIONS: Repositioning of the
GSK3beta-inhibitory drugs improved the prognosis of refractory GBM patients with
active GSK3beta in tumors. Combination of CLOVA cocktail and TMZ is a promising
approach for recurrent GBM.
PMID- 28423559
TI - Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma.
AB - Adrenocortical carcinoma (ACC) is a rare, but aggressive endocrine malignancy
with a generally poor clinical outcome. There is no effective therapy for
advanced and metastatic ACC. In our study, we found that an existing drug
(rottlerin) exerted its tumour-suppressive function in ACC. Specifically,
rottlerin inhibited cellular proliferation of ACC cell lines (NCI-H295R and SW
13) in a dose- and time-dependent manner. We also found that rottlerin induced
cell apoptosis and promoted G0/G1 cell cycle arrest in ACC cell lines. The
cellular migration and invasion of ACC cell lines were decreased after treatment
with rottlerin. Further, the molecular expression of lipoprotein receptor related
protein 6 (LRP6) and beta-catenin were down-regulated in rottlerin-treated ACC
cells, which indicated that Wnt/beta-catenin signaling was involved in the tumour
suppressive function of rottlerin. To further confirm the anti-tumour function of
rottlerin, a nude mouse ACC xenograft model was used. The xenograft growth curves
and TUNEL assays demonstrated that rottlerin inhibited proliferation and induced
apoptosis in the ACC xenograft model. Furthmore, we verified that rottlerin down
regulated the expression of LRP6 and beta-catenin in vivo. The ACC cell line and
xenograft mouse model data indicated that rottlerin significantly inhibited
proliferation and induced apoptosis of ACC cells, likely via suppression of the
Wnt/beta-catenin signaling pathway. Our study indicated the potential therapeutic
utility of rottlerin as a novel and potential chemotherapeutic agent for ACC.
PMID- 28423560
TI - Geraniin attenuates LPS-induced acute lung injury via inhibiting NF-kappaB and
activating Nrf2 signaling pathways.
AB - Geraniin, a typical ellagitannin isolated from Phyllanthusurinaria Linn, has been
reported to have anti-inflammatory effect. The aim of the study is to investigate
the therapeutic effects of geraniin on LPS-induced acute lung injury (ALI) in
mice. The mice were intranasal adminisration of LPS for 12 h. Geraniin was intra
peritoneal injection 1 h after LPS treatment. The results showed that geraniin
significantly attenuated LPS-induced pathological changes in the lung. Geraniin
also inhibited LPS-induced macrophages and neutrophils infiltration in the lung.
Geraniin significantly attenuated LPS-induced elevation of MPO level. LPS-induced
TNF-alpha, IL-6 and IL-1beta production were markedly suppressed by treatment of
geraniin. Furthermore, geraniin inhibited NF-kappaB activation in LPS-induced
ALI. In addition, geraniin was found to up-regulate the expression of Nrf2 and HO
1. In conclusion, these data suggested that geraniin had therapeutic effects in
LPS-induced ALI by inhibiting NF-kappaB and activating Nrf2 signaling pathways.
PMID- 28423561
TI - Dermis, acellular dermal matrix, and fibroblasts from different layers of pig
skin exhibit different profibrotic characteristics: evidence from in vivo study.
AB - To explore the profibrotic characteristics of the autografted dermis, acellular
dermal matrix, and dermal fibroblasts from superficial/deep layers of pig skin,
93 wounds were established on the dorsa of 7 pigs. 72 wounds autografted with the
superficial/deep dermis and acellular dermal matrix served as the
superficial/deep dermis and acellular dermal matrix group, respectively, and were
sampled at 2, 4, and 8 weeks post-wounding. 21 wounds autografted with/without
superficial/deep dermal fibroblasts served as the superficial/deep dermal
fibroblast group and the control group, respectively, and were sampled at 2 weeks
post-wounding. The hematoxylin and eosin staining showed that the wounded skin
thicknesses in the deep dermis group (superficial acellular dermal matrix group)
were significantly greater than those in the superficial dermis group (deep
acellular dermal matrix group) at each time point, the thickness of the cutting
plane in the deep dermal fibroblast group was significantly greater than that in
the superficial dermal fibroblast group and the control group. The western blots
showed that the alpha-smooth muscle actin expression in the deep dermis group
(superficial acellular dermal matrix group) was significantly greater than that
in the superficial dermis group (deep acellular dermal matrix group) at each time
point. In summary, the deep dermis and dermal fibroblasts exhibited more
profibrotic characteristics than the superficial ones, on the contrary, the deep
acellular dermal matrix exhibited less profibrotic characteristics than the
superficial one.
PMID- 28423562
TI - Circulating tumor cells in early stage lung adenocarcinoma: a case series report
and literature review.
AB - PURPOSE: The study aimed to monitor circulating tumor cells (CTCs) in early stage
lung adenocarcinoma patients. RESULTS: CTCs were characterized and classified to
epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-)
CTCs, as per epithelial-mesenchymal transition(EMT) biomarkers. CTCs could not be
found in healthy controls. However, in cohort A, CTCs were found in 17 (17/18)
cases. Detection rate of E-CTCs was lower (5/18) compared with M-CTC (10/18) or
E&M-CTC (14/18). Highly abundant M-CTCs were prone to being in the tumors > 2 cm.
In cohorts A and B, CTCs count increased significantly in all patients with tumor
progression (7/7). Higher CTCs level or change range could be found
postoperatively in the patients with tumor progression, as compared with patients
with disease free survival (P < 0.01). Additionally, CTCs detected by CanPatrolTM
could be validated by CytoploRare or Pep@MNPs. MATERIALS AND METHODS: We included
four cohorts of patients and 20 healthy controls. In cohort A, CTCs were detected
by a newly established approach, i.e., CanPatrolTM, prior to anesthesia and
monitored after operation longitudinally. In cohort B, CTCs were not assessed
prior to operation, but were longitudinally detected after operation. For
validation, we detected FOLR(+)-CTCs by using CytoploRare and EPCAM(+)-CTCs by
using Pep@MNPs prior to operation, in cohorts C and D, respectively. CONCLUSION:
CTCs can be detected in early stage lung adenocarcinoma, even in adenocarcinoma
in situ, and CTCs detection can effectively monitor tumor progression. The
distinguishing of biomarkers of highly invasive and aggressive CTCs warrants
further robust study.
PMID- 28423563
TI - Regulation of p53wt glioma cell proliferation by androgen receptor-mediated
inhibition of small VCP/p97-interacting protein expression.
AB - The incidence of glioma in men is higher than that in women; however, little is
known about the expression and basic function of the androgen receptor (AR) in
gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the
transcriptional level was previously reported. The present study shows that the
protein level of AR is highly expressed in cell lines of the nervous system.
Moreover, the AR expression is increased while SVIP expression is decreased in
tumor tissue of glioma patients, which is in agreement with the progressing WHO
grades. A statistically significant increase in serum testosterone level of
glioma patients compared with that of non-cancer patients was also detected.
Furthermore, it has been proved that SVIP is down-regulated as well as AR is up
regulated in glioma cell lines with R1881 treatment. Interestingly, the depletion
of SVIP using siRNA facilitated cell proliferation and decreased p53 expression.
In addition, overexpression of SVIP increased cell death only in p53wt cell
lines. Moreover, U87MG cells, p53wt cell line was susceptible to AR antagonists
in vitro and in vivo. The current study provides insight into the biological role
of AR in suppressing SVIP and p53 and promoting the progression of glioma as well
as the clinical treatment of glioma patients.
PMID- 28423564
TI - Hypermethylation of the CHRDL1 promoter induces proliferation and metastasis by
activating Akt and Erk in gastric cancer.
AB - CHRDL1 (Chordin-like 1) is a secreted protein that acts as an antagonist of bone
morphogenetic protein (BMP). BMP plays a role as an activator of BMP receptor II
(BMPR II), which mediates extracellular to intracellular signal transmission and
is involved in carcinogenesis and metastasis. Herein, we report that CHRDL1
expression was significantly down-regulated in gastric cancer tissues and
associated with poor survival. Clinic-pathological parameters demonstrated a
close relationship between low CHRDL1 expression and metastasis. In vitro, CHRDL1
knockdown promoted tumor cell proliferation and migration through BMPR II by
activating Akt, Erk and beta-catenin. Furthermore, we observed the
hypermethylation of the CHRDL1 promoter in gastric cancer, which induced low
expression of CHRDL1 and decreased its secretion to the supernatant. Finally, in
vivo experiments confirmed that CHRDL1 acted as a tumor suppressor gene in
suppressing tumor growth and metastasis.
PMID- 28423565
TI - Identification and characterization of L1-specific endo-siRNAs essential for
early embryonic development in pig.
AB - Small noncoding RNAs (sncRNAs) play important roles in RNA interference (RNAi).
In addition to microRNA (miRNA) and Piwi-interacting RNA (piRNA), one key member
of sncRNAs group is endogenous small interfering RNA (endo-siRNA). Some studies
do show the role of endo-siRNAs in Dicer and/or Ago mutants, however, the
biological functions of specific endo-siRNAs remains mostly unanswered. In the
study, we have performed a comparative analysis of endo-siRNAs present in porcine
sperms, oocytes and zygotes, identified by deep sequencing and bioinformatics
analysis. Further, we observe a large amount of endo-siRNAs specific binding on
ORF2 and 3' UTR of porcine L1 (L1-siRNAs). And, 9 L1-siRNAs generated from a
dsRNA formed between L1 transcript and a newly identified an antisense noncoding
RNA was characterized. We show the L1-siRNAs regulate early embryonic development
by inhibiting the activity of L1 retrotransposition. This work can contribute to
understanding the functional role of abundant endo-siRNAs in embryonic
development.
PMID- 28423566
TI - The diagnostic role of microRNA-34a in breast cancer: a systematic review and
meta-analysis.
AB - BACKGROUND: MicroRNA-34a (miR-34a) is a master regulator of tumor suppression in
breast cancer (BC). This systematic review aims to analyze the diagnostic
accuracy of miR-34a in the detection of BC as a biomarker. RESULTS: A total of
1858 BC cases and 494 controls from thirteen eligible studies reported in 9
publications were included. The overall pooled sensitivity, specificity, negative
likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds
ratio (DOR) were 85.50% (95% CI: 83.80-87.00%), 70.00% (95% CI: 65.80-74.10%),
0.29 (95% CI: 0.19-0.43), 2.58 (95% CI: 1.91-3.43), and 9.39 (95% CI: 5.47
16.12), respectively. Similarly, the overall area under the curve (AUC) of the
summary receiver operating characteristic (SROC) was 0.80, indicating the high
conservation of miR-34a as a biomarker. Furthermore, subgroup analysis suggested
that the use of miR-34a as a biomarker is more accurate in tissue-based sample of
invasive BC. We also indicated that miR-34a is a capable biomarker in diagnosing
BC in people of Caucasian descent. MATERIALS AND METHODS: A systematic search was
conducted for eligible publications that address miR-34a expression level in BC
cases and noncancerous controls. Diagnostic capacity of miR-34a for BC was
assessed using pooled sensitivity and specificity, DOR, and AUC of SROC. PLR and
NLR were verified to estimate the miR-34a diagnostic accuracy in clinical level.
The quality of the included studies was assessed by QUADAS-2. CONCLUSIONS: These
findings suggest miR-34a is a promising non-invasive biomarker in diagnosing BC.
Well-designed cohort studies should be implemented to warrant the diagnostic
value of miR-34a in clinical purposes.
PMID- 28423567
TI - CXCR1/2 pathways in paclitaxel-induced neuropathic pain.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain
that represents a frequent and serious consequence of chemotherapy agents. Over
the last years, significant progress has been achieved in elucidating the
underlying pathogenesis of CIPN. The interference of taxanes with microtubule has
been proposed as a mechanism that leads to altered axonal transport and to
permanent neurological damages. The inflammatory process activated by
chemotherapeutic agents has been considered as a potential trigger of nociceptive
process in CIPN.In this study we investigated the effect of reparixin, an
inhibitor of CXCR1/CXCR2, in suppressing the development of paclitaxel-induced
nociception in rats. Moreover, reparixin activity in reversing the neurotoxic
effects induced by paclitaxel or GRO/KC in F11 cells was also analyzed.Reparixin
administered by continuous infusion ameliorated paclitaxel-induced mechanical and
cold allodynia in rats. In F11 cells, reparixin was able to inhibit the increase
of acetyladed alpha-tubulin induced both by paclitaxel and GRO/KC. The subsequent
experiments were performed in order to dissect the signal transduction pathways
under GRO/KC control, eventually modulated by paclitaxel and/or reparixin. To
this aim we found that reparixin significantly counteracted p-FAK, p-JAK2/p
STAT3, and PI3K-p-cortactin activation induced either by paclitaxel or
GRO/KC.Overall the present results have identified IL-8/CXCR1/2 pathway as a
mechanism involved in paclitaxel-induced peripheral neuropathy. In particular,
the obtained data suggest that the inhibition of CXCR1/2 combined with standard
taxane therapy, in addition to potentiating the taxane anti-tumor activity can
reduce chemotherapy-induced neurotoxicity, thus giving some insight for the
development of novel treatments.
PMID- 28423568
TI - Sepia ink oligopeptide induces apoptosis and growth inhibition in human lung
cancer cells.
AB - Sepia ink oligopeptide (SIO), as a tripeptide extracted from Sepia ink, could be
used as an inducer of apoptosis in human prostate cancer cells. We designed a
cyclo-mimetic peptide of SIO by introducing a disulfide bond to stabilize the
native peptide into beta turn structure, and produced a peptide with higher cell
permeability and stability. Through labeling an FITC to the N-terminus of the
peptide, the cell permeability was examined. Stabilized peptide showed enhanced
cellular uptake than linear tripeptide as indicated by flow cytometry and cell
fluorescent imaging. The high intracellular delivery of stable SIO could more
efficiently inhibit cell proliferation and induce apoptosis. Furthermore, the
expression of the anti-apoptotic protein Bcl-2 was down-regulated, whereas pro
apoptotic proteins P53 and caspase-3 were up-regulated by stable SIO. In
conclusion, our study is the first to use stable SIO to induce apoptosis in two
lung cancer cells A549 and H1299.
PMID- 28423569
TI - Accurate prediction of protein-protein interactions by integrating potential
evolutionary information embedded in PSSM profile and discriminative vector
machine classifier.
AB - Identification of protein-protein interactions (PPIs) is of critical importance
for deciphering the underlying mechanisms of almost all biological processes of
cell and providing great insight into the study of human disease. Although much
effort has been devoted to identifying PPIs from various organisms, existing high
throughput biological techniques are time-consuming, expensive, and have high
false positive and negative results. Thus it is highly urgent to develop in
silico methods to predict PPIs efficiently and accurately in this post genomic
era. In this article, we report a novel computational model combining our newly
developed discriminative vector machine classifier (DVM) and an improved Weber
local descriptor (IWLD) for the prediction of PPIs. Two components, differential
excitation and orientation, are exploited to build evolutionary features for each
protein sequence. The main characteristics of the proposed method lies in
introducing an effective feature descriptor IWLD which can capture highly
discriminative evolutionary information from position-specific scoring matrixes
(PSSM) of protein data, and employing the powerful and robust DVM classifier.
When applying the proposed method to Yeast and H. pylori data sets, we obtained
excellent prediction accuracies as high as 96.52% and 91.80%, respectively, which
are significantly better than the previous methods. Extensive experiments were
then performed for predicting cross-species PPIs and the predictive results were
also pretty promising. To further validate the performance of the proposed
method, we compared it with the state-of-the-art support vector machine (SVM)
classifier on Human data set. The experimental results obtained indicate that our
method is highly effective for PPIs prediction and can be taken as a
supplementary tool for future proteomics research.
PMID- 28423570
TI - Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as
novel biomarkers for systemic lupus erythematosus.
AB - Despite increasing evidence that long non-coding RNAs (lncRNAs) widely take part
in human diseases, the role of lncRNAs in systemic lupus erythematosus (SLE) is
largely unknown. In this study, we performed a two-stage study to explore the
plasma levels of five lncRNAs (GAS5, linc0949, linc0597, HOTAIRM1 and lnc-DC) and
their potential as SLE biomarkers. Compared with healthy controls, plasma levels
of GAS5 and lnc-DC were significantly decreased (P < 0.001 and P = 0.002,
respectively) while linc0597 were overexpressed in SLE patients (P < 0.001). When
SLE patients were divided into SLE without nephritis and lupus nephritis (LN),
the levels of lnc-DC were significantly higher in LN compared with SLE without
nephritis (P = 0.018), but no significant difference in levels of GAS5 and
linc0597 were found between LN and SLE without nephritis; plasma linc0949 level
showed no significant difference in all comparisons. Further evaluation on
potential biomarkers showed that GAS5, linc0597 and lnc-DC may specifically
identify patients with SLE, the combination of GAS5 and linc0597 provided better
diagnostic accuracy; lnc-DC may discriminate LN from SLE without nephritis. In
summary, GAS5, linc0597 and lnc-DC in plasma could be potential biomarkers for
SLE.
PMID- 28423571
TI - Predictive analysis of long non-coding RNA expression profiles in diffuse large B
cell lymphoma.
AB - Long non-coding RNAs (lncRNAs) are implicated in many tumors. To find novel
targets for study of diffuse large B-cell lymphoma (DLBCL), our team performed
genome-wide analyses of lncRNA expression in 5 DLBCL cell lines using the 4*180K
Agilent lncRNA Chip system, and in normal B cells. Five lncRNAs were validated by
quantitative reverse transcription polymerase chain reaction. The differentially
expressed lncRNAs and mRNAs were identified via false discovery rate and fold
change filtering. Potential targets correlated with DLBCL were recognized via
gene ontology and pathway analysis. Establishment of the co-expression network
was done using Cytoscape. In total, 1053 lncRNAs and 4391 mRNAs were dysregulated
in DLBCL cells, being comparing with normal B cells. The results suggested that
the expressions of the 5 lncRNAs were consistent with the chip results. Several
terms including the cell cycle, apoptosis, B cell receptor and NF-kappaB
signaling pathways were important in the progression of DLBCL. The chromosome
locations of a few lncRNAs and the associated coexpressed genes were demonstrated
by cis-regulatory gene analyses. The results of trans-analyses showed that
multiple transcription factors regulated lncRNA and gene expression. Those
outstanding lncRNAs in each group were implicated in the regulation of the TF
lncRNA-target gene network. Our study identified a set of lncRNAs differentially
expressed in DLBCL cells.
PMID- 28423572
TI - Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific
marker of breast and colorectal cancer.
AB - Changes in blood epigenetic age have been associated with several pathological
conditions and have recently been described to anticipate cancer development. In
this work, we analyze a publicly available leukocytes methylation dataset to
evaluate the relation between DNA methylation age and the prospective development
of specific types of cancer. We calculated DNA methylation age acceleration using
five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and
two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the
EPIC-Italy project and we compared 424 samples that remained cancer-free over the
approximately ten years of follow-up with 235 and 166 subjects who developed
breast and colorectal cancer, respectively. We show that the epigenetic age
estimated from blood DNA methylation data is statistically significantly
associated to future breast and male colorectal cancer development. These results
are corroborated by survival analysis that shows significant association between
age acceleration and cancer incidence suggesting that the chance of developing
age-related diseases may be predicted by circulating epigenetic markers, with a
dependence upon tumor type, sex and age estimator. These are encouraging results
towards the non-invasive and perspective usage of epigenetic biomarkers.
PMID- 28423573
TI - Involvement of AF1q/MLLT11 in the progression of ovarian cancer.
AB - The functional role of AF1q/MLLT11, an oncogenic factor involved in a
translocation t(1;11)(q21;q23) responsible for acute myeloid leukaemia, has been
investigated in hematological and solid malignancies and its expression was found
to be linked to tumor progression and poor clinical outcome. In addition to its
oncogenic function, AF1q has been shown to play a role in the onset of basal and
drug-induced apoptosis in cancer cells of different histotypes, including ovarian
cancer. Through in vitro, ex vivo, and in silico approaches, we demonstrated here
that AF1q is also endowed with protumorigenic potential in ovarian cancer. In
ovarian cancer cell lines, stable AF1q overexpression caused activation of
epithelial-to-mesenchymal transition and increased motility/migratory/invasive
abilities accompanied by gene expression changes mainly related to Wnt signaling
and to signaling pathways involving in ERK/p38 activation. The potential role of
AF1q in ovarian cancer progression was confirmed by immunohistochemical and in
silico analyses performed in ovarian tumor specimens which revealed that the
protein was absent in normal ovarian epithelium and became detectable when
atypical proliferation was present. Moreover, AF1q was significantly lower in
borderline ovarian tumors (i.e., tumors of low malignant potential without
stromal invasion) than in invasive tumors, thus corroborating the association
between high AF1q expression and increased migratory/invasive cell behavior and
confirming its potential role in ovarian cancer progression. Our findings
demonstrated, for the first time, that AF1q is endowed with protumorigenic
activity in ovarian cancer, thus highlighting a dual behavior (i.e.,
protumorigenic and proapoptotic functions) of the protein in the malignancy.
PMID- 28423574
TI - Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular
carcinoma.
AB - Drug resistance to sorafenib is common in patients with hepatocellular
carcinoma(HCC). We examined the effects of a combination of sorafenib and
fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced
apoptosis and reduced cellular viability in HCC more effectively than either drug
alone. The combination treatment also inhibited activation of hepatic stellate
cells, whereas single drug treatments did not. On a molecular level, combined
treatment inhibited activation of the MAPK and NF-kappaB pathways via Toll-like
receptor 4 in HCC cells. Combined treatment also inhibited expression of stromal
cell-derived factor 1alpha in HCC cells, which further inhibited the MAPK pathway
in hepatic stellate cells. These results suggest that a combination of sorafenib
and fluvastatin may be a promising therapeutic strategy for patients with
advanced HCC.
PMID- 28423575
TI - Activated Notch signaling augments cell growth in hepatocellular carcinoma via up
regulating the nuclear receptor NR4A2.
AB - Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional
therapies are limited due to the human liver being such a unique organ and easily
showing side-effects. The unclear molecular mechanisms are tough challenges for
scientists searching for new and effective anti-HCC targeting drugs. We
identified that the nuclear receptor NR4A2 is a novel oncogene in HCC
progression. In this study, we show that NR4A2 and the notch recceptor Notch1
were expressed highly in primary HCC tissues and immortal HCC cells by using
qPCR, western blot and immuno-histochemistry assays. Both genes were observed to
stimulate HCC cell proliferation, anti-apoptosis and cell cycle arrest by using
cell proliferation assays and FACS assays. We also observed that the four notch
receptor subtypes (Notch1-4) displayed different effects on HCC cell growth. The
over-expression of Notch1 by transiently transfecting the intracellular domain of
Notch1 (ICN1, Notch1 active form) increased the expression of NR4A2, with the
knockdown of Notch1 decreasing NR4A2. This indicates that NR4A2 is one of the
Notch-mediated downstream genes. Moreover, both NR4A2 and Notch1 suppressed the
expression of tumor suppressors p21 and p63. These findings support that
Notch1/NR4A2 co-regulate HCC cell functions by playing oncogenic roles and
regulating the associated downstream signaling pathways. Novel Notch1/NR4A2
mediated oncogenic signaling may provide us a great opportunity for anti-HCC drug
development.
PMID- 28423576
TI - Solitary ground-glass opacity nodules of stage IA pulmonary adenocarcinoma:
combination of 18F-FDG PET/CT and high-resolution computed tomography features to
predict invasive adenocarcinoma.
AB - To investigate the performance of combined 18F-FDG Positron Emission
Tomography/Computed Tomography with high-resolution CT for differentiating
invasive adenocarcinoma from adenocarcinoma in situ (pre-invasive lesion) or
minimally invasive adenocarcinoma in stage IA lung cancer patients with solitary
ground-glass opacity nodules. This retrospective study enrolled 58 consecutive
stage IA pulmonary adenocarcinoma patients with solitary ground-glass opacity
nodules. The characteristics and measurements of the ground-glass opacity nodules
as pure ground-glass opacity nodules and mixed ground-glass opacity nodules in
the pre-invasive or minimally invasive adenocarcinoma and invasive adenocarcinoma
groups on Positron Emission Tomography/Computed Tomography and high-resolution CT
were compared and analyzed. Ground-glass opacity nodules in the pre-invasive or
minimally invasive adenocarcinoma group preferentially manifested as pure ground
glass opacity nodule (p < 0.01) compared to the invasive adenocarcinoma group.
While cystic appearance was more common in the invasive adenocarcinoma group (p <
0.05). Significant differences were found in the diameter of the ground-glass
opacity nodule itself and its solid component, and consolidation/tumor ratio
between the two groups. The sensitivity in predicting invasive adenocarcinoma was
higher with a combined consolidation/tumor ratio > 0.38 and SUVmax > 1.46 in
mixed ground-glass opacity nodule when compared to those of SUVmax > 0.95 alone
or consolidation/tumor ratio> 0.39 alone (both p > 0.05). For a mixed ground
glass opacity nodule combined consolidation/tumor ratio > 0.38 and SUVmax > 1.46
appears to better predict invasive adenocarcinoma in stage IA lung cancer
patients with solitary ground-glass opacity nodules.
PMID- 28423577
TI - The cyclin-like protein, SPY1, regulates the ERalpha and ERK1/2 pathways
promoting tamoxifen resistance.
AB - The Ras/Raf/MEK/ERK pathway conveys growth factor and mitogen signalling to
control the phosphorylation of a plethora of substrates regulating proliferation,
survival, and migration. The Ras signalling pathway is frequently associated with
poor prognosis and drug resistance in various cancers including those of the
blood, breast and prostate. Activation of the downstream effector ERK does not
always occur via a linear cascade of events; complicating the targeting of this
pathway therapeutically. This work describes a novel positive feedback loop where
the cell cycle regulatory factor Spy1 (RINGO; gene SPDYA) activates ERK1/2 in a
MEK-independent fashion. Spy1 was originally isolated for the ability to
stimulate Xenopus oocyte maturation via a MAPK-signalling pathway and is known to
override apoptosis triggered by the DNA damage response. We demonstrate that
mammalian Spy1-mediated ERK activation increases ligand-independent
phosphorylation and activation of estrogen receptor alpha, correlating with a
decrease in tamoxifen sensitivity. This could define a novel druggable mechanism
driving proliferation and resistance in select cancers.
PMID- 28423578
TI - Endothelial microparticles delivering microRNA-155 into T lymphocytes are
involved in the initiation of acute graft-versus-host disease following
allogeneic hematopoietic stem cell transplantation.
AB - Endothelial microparticles (EMPs) upregulation has been observed in acute graft
versus-host disease (aGVHD) after allogeneic hematopoietic stem cell
transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found
that EMPs derived from TNF-alpha-stimulated human umbilical vein endothelial
cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal
cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice
were remarkably elevated and significantly higher than the levels in plasma.
Moreover, the rising peak of miR-155 in MPs occurred significantly prior to the
peak in T lymphocytes. Additionally, we observed fluorescently-labeled miR-155 in
EMPs actively transported into recipient T lymphocytes. Inhibition of miR-155 in
EMPs by antagomir-155 did not influence the proliferation and apoptosis of T
lymphocytes, but induced defective differentiation toward Th1, Th9 and Th17 cells
and skewed differentiation toward Th2 and Treg cells. Furthermore, intravenous
injection of miR-155-deficient-EMPs into aGVHD mice significantly attenuated the
exacerbation of aGVHD manifestations and abnormal T lymphocytes differentiation
induced by high concentration EMPs. Taken together, these data provide a
mechanistic framework in which miR-155 delivered by EMPs is involved in aGVHD
pathogenesis by activating specific T lymphocytes functions. The results may
provide new therapeutic approaches for aGVHD while preserving graft-versus
leukemia (GVL) effect.
PMID- 28423579
TI - Systematic review with network meta-analysis: comparative efficacy of different
enteral immunonutrition formulas in patients underwent gastrectomy.
AB - OBJECTIVES: Optimal enteral immunonutrition (EIN) regime for gastric cancer (GC)
patients underwent gastrectomy remains uncertainty. To assess comparative
efficacy of different EIN formulas in GC patients underwent gastrectomy, we
performed network meta-analysis. RESULTS: We included 11 RCTs enrolling 840
patients. Pairwise meta-analysis indicated that EIN (RR 0.56, 95% CI 0.36-0.86;
MD -0.42, 95% CI -0.74-0.10), Arg+RNA+omega-3-FAs (RR 0.37, 95% CI 0.22-0.63; MD
0.42, 95% CI -0.75-0.07), Arg+Gln+omega-3-FAs (RR 0.22, 95% CI 0.05-0.94; MD
0.69, 95% CI -1.22-1.07) reduced ICs and LOS. Network meta-analysis confirmed the
potential of Arg+RNA+omega-3-FAs for ICs (OR 0.27, 95% Crl 0.12-0.49) and
Arg+Gln+omega-3-FAs for CIs (OR 0.22, 95% Crl 0.02-0.84) and LOS (SMD -0.63, 95%
Crl -1.07-0.13), and indicated that Arg+RNA+omega-3-FAs was superior to Arg+RNA
and Arg+Gln for ICs as well. MATERIALS AND METHODS: We performed direct and
network meta-analyses for randomized controlled trials comparing EIN formulas
with each other or standard enteral nutrition (SEN) in reducing infectious
complications (ICs), noninfectious complications (NICs) and length of hospital
stay (LOS), through January 2016. The surface under the cumulative ranking curve
(SCURA) and Grading of Recommendations Assessment, Development and Evaluation
(GRADE) were used to rank regimes and rate qualities of evidences respectively.
CONCLUSIONS: As for GC patients underwent gastrectomy, Arg+RNA+omega-3-FAs and
Arg+Gln+omega-3-FAs are the optimal regimes of reducing ICs and LOS.
PMID- 28423580
TI - Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes hypoxia-induced glioma
migration and invasion.
AB - Poor prognosis of glioblastoma multiforme is strongly associated with the ability
of tumor cells to invade the brain parenchyma, which is believed to be the major
factor responsible for glioblastoma recurrence. Therefore, identifying the
molecular mechanisms driving invasion may lead to the development of improved
therapies for glioblastoma patients. Here, we investigated the role of
procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing
collagen cross-linking, in the biology of glioblastoma invasion. PLOD2 mRNA was
significantly overexpressed in glioblastoma compared to low-grade tumors based on
the Oncomine datasets and REMBRANDT database for human gliomas. Kaplan-Meier
estimates based on the TCGA dataset demonstrated that high PLOD2 expression was
associated with poor prognosis. In vitro, hypoxia upregulated PLOD2 protein in
U87 and U251 human glioma cell lines. siRNA knockdown of endogenous HIF-1alpha or
treatment of cells with the HIF-1alpha inhibitor PX-478 largely abolished the
hypoxia-mediated PLOD2 upregulation. Knockdown of PLOD2 in glioma cell lines led
to decreases in migration and invasion under normoxia and hypoxia. In addition,
levels of phosphorylated FAK (Tyr 397), an important kinase mediating cell
adhesion, were reduced in U87-shPLOD2 and U251-shPLOD2 cells, particularly under
hypoxic conditions. Finally, orthotopic U251-shPLOD2 xenografts were
circumscribed rather than locally invasive. In conclusion, the results indicated
that PLOD2 was a gene of clinical relevance with implications in glioblastoma
invasion and treatment strategies.
PMID- 28423581
TI - DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal
squamous cell carcinoma.
AB - Oropharyngeal squamous cell carcinomas (OPSCC) are common, have poor outcomes,
and comprise two biologically and clinically distinct diseases. While OPSCC that
arise from human papillomavirus infections (HPV+) have better overall survival
than their HPV- counterparts, the incidence of HPV+ OPSCC is increasing
dramatically, affecting younger individuals which are often left with life-long
co-morbidities from aggressive treatment. To identify patients which do poorly
versus those who might benefit from milder regimens, risk-stratifying biomarkers
are now needed within this population. One potential marker is the DEK
oncoprotein, whose transcriptional upregulation in most malignancies is
associated with chemotherapy resistance, advanced tumor stage, and worse
outcomes. Herein, a retrospective case study was performed on DEK protein
expression in therapy-naive surgical resections from 194 OPSCC patients. We found
that DEK was associated with advanced tumor stage, increased hazard of death, and
interleukin IL6 expression in HPV16+ disease. Surprisingly, DEK levels in HPV16-
OPSCC were not associated with advanced tumor stage or increased hazard of death.
Overall, these findings mark HPV16- OPSCC as an exceptional malignancy were DEK
expression does not correlate with outcome, and support the potential prognostic
utility of DEK to identify aggressive HPV16+ disease.
PMID- 28423582
TI - Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B
Raf/MAPK/Erk pathway.
AB - Non-small cell lung cancer (NSCLC), one type of lung cancer, owns high rates of
morbidity and mortality. B-Raf is one of the promising oncogenic drivers of
NSCLC. Parthenolide, a natural product, is mainly extracted from the herbal plant
Tanacetum parthenium. The effect of parthenolide on NSCLC cells and its potential
as B-Raf inhibitor were studied in this study. It's shown that parthenolide
exhibited the strong cytotoxicity against NSCLC cells with IC50 ranging from 6.07
+/- 0.45 to 15.38 +/- 1.13 MUM. Parthenolide was also able to induce apoptosis,
suppress proliferation and invasion in NSCLC cells. In terms of the involved
mechanism, parthenolide suppressed GLC-82 cell response via targeting on B-Raf
and inhibiting MAPK/Erk pathway signaling. The effect of parthenolide on B-Raf
and MAPK/Erk pathway was further confirmed by RNA interference of B-Raf.
Decreased expression of c-Myc in protein and mRNA level was also discovered,
which is considered as the further downstream of the MAPK/Erk pathway. In
addition, STAT3 activity inhibition by parthenolide contributed to its effect on
GLC-82 cells, which is independent of PI3K pathway signaling and GSK3. All above
provide an insight to understand the action of parthenolide as a potential B-Raf
inhibitor in treatment of NSCLC.
PMID- 28423583
TI - The protection of meloxicam against chronic aluminium overload-induced liver
injury in rats.
AB - The present study was designed to observe the protective effect and mechanisms of
meloxicam on liver injury caused by chronic aluminium exposure in rats. The
histopathology was detected by hematoxylin-eosin staining. The levels of
prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were
detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases
2, prostaglandin E2 receptors and protein kinase A were measured by western
blotting and immunohistochemistry. Our experimental results showed that aluminium
overload significantly damaged the liver. Aluminium also significantly increased
the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine
monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and
the levels of inflammation and oxidative stress, while significantly decreased
the EP3 expression in liver. The administration of meloxicam significantly
improved the impairment of liver. The contents of prostaglandin E2 and cyclic
adenosine monophosphate were significantly decreased by administration of
meloxicam. The administration of meloxicam also significantly decreased the
expressions of cyclooxygenases-2 and protein kinase A and the levels of
inflammation and oxidative stress, while significantly increased the EP1,2,3,4
expressions in rat liver. Our results suggested that the imbalance of
cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved
in the injury of chronic aluminium-overload rat liver. The protective mechanism
of meloxicam on aluminium-overload liver injury is attributed to reconstruct the
balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.
PMID- 28423584
TI - Hepatocyte growth factor is a prognostic marker in patients with colorectal
cancer: a meta-analysis.
AB - Hepatocyte growth factor (HGF) is a crucial factor associated with development,
progression and metastasis of colorectal cancer (CRC). However, its prognostic
value remains unclear. Thus studies referring to the correlation between HGF and
CRC patients' prognosis were included to explore the role of HGF in CRC. At last
nine articles were included. The results showed that the over-expression of HGF
was associated with a poor prognosis, presented through overall survival (OS,
Hazard ratio (HR) = 2.50, 95% confidence interval (CI): 2.12-2.96) and disease
free survival (DFS, HR = 1.99, 95% CI: 1.59-2.50). Subgroup analysis indicated
that no significant difference was found between the Asian countries (OS: HR =
2.37; DFS: HR = 2.02) and the non-Asian countries (OS: HR = 3.15; DFS: HR =
1.87), between the studies that used univariate analyses (OS: HR = 2.51; DFS: HR
= 2.07) and those that used multivariate analyses (OS: HR = 2.65; DFS: HR =
1.78), and between metastatic CRC (OS: HR = 2.26; DFS: HR = 2.06) and stage I-IV
CRC (OS: HR = 3.08; DFS: HR = 0.70). Our meta-analysis has shown that the over
expression of HGF is valuable in CRC prognosis evaluation. This conclusion should
be further confirmed by large-sample cohort studies.
PMID- 28423585
TI - The rs1550117 A>G variant in DNMT3A gene promoter significantly increases non
small cell lung cancer susceptibility in a Han Chinese population.
AB - In this study, we conducted a case-control study to explore the association
between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung
cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of
rs1550117 A>G variant was performed by polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of
rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals
carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA
genotype carriers. Further stratified analysis showed that rs1550117 A>G was
significantly related to age (> 60 years), male, smoking and drinking. In vivo
detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays
consistently showed that the allele G significantly decreased DNMT3A
transcription. Additional functional analysis revealed that the increased binding
affinity of transcription repressor SP1, which was associated with allele G of
rs1550117, led to the significant decreased expression of DNMT3A. Collectively,
our results propose a suppression role of DNMT3A in NSCLC development and
emphasize the dual roles of DNMT3A in tumorigenesis.
PMID- 28423586
TI - The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of
ovarian cancer cells.
AB - PUMA is a member of the "BH3-only" branch of the BCL-2 family. Our previous study
suggests a therapeutic potential of PUMA in treating ovarian cancer, however, the
action mechanism of PUMA remains elusive. In this work, we found that in PUMA
adenovirus-infected A2780s ovarian cancer cells, exogenous PUMA was partially
accumulated in the cytosol and mainly located to the mitochondria. We further
showed that PUMA induces mitochondrial dysfunction-mediated apoptosis and ROS
generation through functional BAX in a ROS generating enzyme- and caspase
independent manner irrespective of their p53 status, and results in activation of
Nrf2/HO-1 pathway. Furthermore, PUMA induces DNA breaks in gamma-H2AX staining,
and causes activation of DNA damage-related kinases including ATM, ATR, DNA-PKcs,
Chk1 and Chk2, which are correlated with the apoptosis. PUMA also results in ROS
triggered JNK activation. Intriguingly, JNK plays a dual role in both DNA damage
response and apoptosis, and has an additional contribution to apoptosis. Taken
together, we have provided new insight into the action mechanism by which
elevated PUMA first induces ROS generation then results in DNA damage response
and JNK activation, ultimately contributing to apoptosis in ovarian cancer cells.
PMID- 28423587
TI - The correlation between programmed death-ligand 1 expression and driver gene
mutations in NSCLC.
AB - OBJECTIVES: This study aimed to evaluate the correlation between positive PD-L1
expression and driver gene mutations in NSCLC and to seek preliminary evidence in
favor of the strategy of PD-L1 inhibitors plus targeted agents. RESULTS: The
overall analyses revealed that positive PD-L1 expression had a significant
relationship with KRAS status (RR = 1.26; 95% CI, 1.06-1.50, P = 0.010), but no
correlation with clinical characteristics (gender, smoking status, histological
types), driver gene status (EGFR, ALK) and overall survival (OS): male versus
female (RR = 1.16; 95% CI, 0.95-1.42; P = 0.15), never smoking versus
former/current smoking (RR = 0.79; 95% CI, 0.56-1.11; P = 0.17), adenocarcinoma
versus non-adenocarcinoma (RR = 0.94; 95% CI, 0.63-1.41; P = 0.77), EGFR mutation
versus EGFR wild type (RR = 0.74; 95% CI, 0.52-1.06; P = 0.10), ALK positive
versus ALK negative (RR = 1.02; 95% CI, 0.75-1.38; P = 0.91), OS of positive PD
L1 expression versus that of negative PD-L1 expression (HR = 1.31, 95% CI, 0.90
1.90; P = 0.15), respectively. Noteworthily, subgroup analyses exhibited that in
Chinese cohort studies, positive PD-L1 expression was significantly correlated
with OS (HR = 1.75, 95% CI, 1.36-2.24, P < 0.0001); and in the studies using PD
L1 monoclonal antibodies (McAbs), positive PD-L1 expression was significantly
correlated with KRAS mutation (RR = 1.32, 95% CI, 1.06-1.65, P = 0.01) and EGFR
mutation (RR = 0.51, 95% CI, 0.28-0.93, P = 0.03). MATERIALS AND METHODS: After
thoroughly searching PubMed, EMBASE and Cochrane Library databases, 11 relevant
studies incorporating 3128 cases were identified. The pooled data were analyzed
via Review manager 5.3 software. CONCLUSIONS: PD-L1 inhibitors probably was a
potential promising option to manage advanced NSCLC harboring KRAS mutation.
PMID- 28423588
TI - Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated
increase in CA916798.
AB - The tyrosine phosphatase Shp2 is associated with tumorigenesis in small cell lung
cancer (SCLC). However, the relationship between Shp2 and resistance to
chemotherapy remains unclear. Here, we show that Shp2 plays an important role in
inducing resistance to cisplatin-based chemotherapy via the SHP2-AKT-CA916798
pathway. In an SCLC cell line, overexpression of Shp2 induced cisplatin
resistance and the increased expression of AKT, pAKT, pmTOR, and CA916798.
Conversely, depletion of Shp2 in a cisplatin-resistant cell line via RNA
interference increased cisplatin sensitivity and decreased AKT, pAKT, pmTOR, and
CA916798 expression levels. Activation of AKT stimulated CA916798 expression and
altered the level of Shp2. A mouse xenograft model verified the results obtained
from the in vitro experiments. In addition, we collected and analyzed clinical
SCLC specimens and found that Shp2 levels correlated with CA916798 expression in
tumor tissues. Importantly, higher levels of Shp2 or CA916798 were associated
with a poorer prognosis in SCLC patients who received chemotherapy. Together, our
findings indicate that Shp2 induces cisplatin resistance in SCLC patients via the
SHP2-AKT-CA916798 pathway. Therefore, Shp2 and CA916798 may be promising
biomarkers for predicting resistance to chemotherapy and may function as targets
for enhancing treatments.
PMID- 28423589
TI - Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by
targeting PDCD4 gene.
AB - This study aims to explore the effects of microRNA-21 (miR-21) on
radiosensitivity in non-small cell lung cancer (NSCLC) by targeting programmed
cell deanth 4 (PDCD4) and regulating PI3K/AKT/mTOR signaling pathway. Cancer
tissues and adjacent normal tissues were collected from 97 NSCLC patients who
received a standard radiotherapy regimen. TUNEL assay was applied to determine
cell apoptosis in tissues. The qRT-PCR assay was used to detect the expressions
of miR-21 expression and PDCD4 mRNA. The protein expressions of PDCD4 and
PI3K/AKT/mTOR signaling pathway-related proteins were determined by Western
blotting. Colony formation assay was used to observe the sensitivity to
radiotherapy of NSCLC cells. Flow cytometry was adopted to testify cell
apoptosis. Compared with adjacent normal tissues, miR-21 expression was
significantly increased and the mRNA and protein expressions of PDCD4 were
decreased in NSCLC tissues. Higher miR-21 expression was associated with
attenuated radiation efficacy and shorter median survival time. PDCD4 was the
target gene of miR-21. The miR-21 mimics and siRNA-PDCD4 decreased the
sensitivity to radiotherapy and cell apoptosis of A549 and H1299 cells and
activated PI3K/AKT/mTOR pathway. The sensitivity of A549 and H1299 cells was
strengthened in the miR-21 inhibitors group and the PI3K/AKT/mTOR inhibitors
group. The siRNA-PDCD4 could reverse the effects of miR-21 inhibitors on
sensitivity to radiotherapy and cell apoptosis of NSCLC cells. Our findings
provide strong evidence that miR-21 could inhibit PDCD4 expression and activate
PI3K/AKT/mTOR signaling pathway, thereby affecting the radiation sensitivity of
NSCLC cells.
PMID- 28423590
TI - Neutralization of interleukin-17 suppresses allergic rhinitis symptoms by
downregulating Th2 and Th17 responses and upregulating the Treg response.
AB - Allergic rhinitis (AR) has long been considered to predominantly involve the
actions of Th2 cells, with relatively small contributions from Th1 cells. In
recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered
the Th1/Th2 balance paradigm more complex and expanded our understanding of the
pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to
induce allergen-specific Th2 cell activation, eosinophil and neutrophil
accumulation, and serum IgE production in asthma; all of these features may play
important roles in AR. To the best of our knowledge, only a few studies have
assessed the feasibility of using IL-17 antagonists to treat AR. Thus, the
principal objectives of the present study were, first, to determine the status of
Th17 and Treg cells in the nasal mucosa of a mouse model of AR, and, second, to
investigate the effects of IL-17 on such cells and the therapeutic efficacy of
anti-IL-17 antibodies (Abs) in the context of AR. Anti-IL-17 Abs were given
intranasally during the re-challenge of BALB/c mice with ovalbumin (OVA)-induced
AR. We measured the numbers of nasal rubbing motions and sneezes, eosinophil and
neutrophil levels, Th1, Th2, Th17, and Treg parameters in the nasal mucosa. Anti
IL-17 Abs markedly reduced the number of nasal rubbing motions and sneezes,
decreased eosinophil and neutrophil infiltration, reduced Th2 and Th17 responses,
and increased the Treg response. Anti-IL-17 Ab treatment protects against AR.
These results will improve our understanding of AR pathogenesis and may lead to
the development of novel therapeutic approaches for management of the condition.
PMID- 28423591
TI - PIK3CA mutation and colorectal cancer precision medicine.
PMID- 28423592
TI - Protective effect of hydrogen sulphide against myocardial hypertrophy in mice.
AB - Cardiac hypertrophy is a critical component of phenotype in the failing heart.
Recently, increasing evidence has demonstrated that oxidative stress plays an
important role in the pathogenesis of myocardial hypertrophy. In the present
study, we generated a mouse model of transverse aortic constriction (TAC) to
investigate whether hydrogen sulfide (H2S) has protective effects against cardiac
hypertrophy. Left ventricular structure was analyzed by two-dimensional
echocardiography. Oxidative stress was evaluated by measuring malondialdehyde,
superoxide dismutase, glutathione peroxidase and reactive oxygen specie in the
myocardium. Angiotensin II (Ang-II) was used to induce cardiomyocyte hypertrophy.
Neonatal rat cardiomyocytes pretreated with H2S donor sodium hydrosulfide prior
to Ang-II exposure were used to determine the involvement of Nrf2 and PI3K/Akt
pathway in the antioxidant effects of H2S. Our findings showed that H2S could
protect against cardiac hypertrophy by attenuating oxidative stress. The
antioxidant roles of H2S in myocardial hypertrophy probably depend on the
activation of PI3K/Akt signaling, which consequently increases Nrf2 activity and
HO-1 and GCLM expression. In summary, H2S may exert antioxidant effect on cardiac
hypertrophy via PI3K/Akt-dependent activation of Nrf2 pathway.
PMID- 28423593
TI - Anti-cancer effect of novel PAK1 inhibitor via induction of PUMA-mediated cell
death and p21-mediated cell cycle arrest.
AB - Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human
cancer and speculated as a target of novel anti-tumor drug. In previous, we also
showed that PAK1 is highly activated in the Smad4-deficient condition and
suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding
and phosphorylation. On the basis of this result, we have tried to find novel
PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library
screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA),
which selectively blocks the PAK1-PUMA binding and also suppresses cell
proliferation via PUMA-dependent manner. Indeed, in PUMA-deficient cells, this
chemical did not show anti-proliferating effect. This chemical possessed very
strong PAK1 inhibition activity that it suppressed BAD (Bcl-2-asoociated death
promoter) phosphorylation and meta-phase arrest via Aurora kinase inactivation in
lower concentration than that of previous PAK1 kinase, FRAX486 and AG879.
Moreover, our chemical obviously induced p21/WAF1/CIP1 (Cyclin-dependent kinase
inhibitor 1A) expression by releasing from Bcl-2 (B-cell lymphoma-2) and by
inhibition of AKT-mediated p21 suppression. Considering our result, IPP-14 and
its derivatives would be possible candidates for PAK1 and p21 induction targeted
anti-cancer drug.
PMID- 28423594
TI - The hypoxia-activated prodrug evofosfamide in combination with multiple regimens
of radiotherapy.
AB - The promising treatment combination of ionizing radiation (IR) with a hypoxia
activated prodrug (HAP) is based on biological cooperation. Here we investigated
the hypoxia-activated prodrug evofosfamide in combination with different
treatment regimens of IR against lung A549- and head&neck UT-SCC-14-derived tumor
xenografts. DNA damage-related endpoints and clonogenic cell survival of A549 and
UT-SCC-14 carcinoma cells were probed under normoxia and hypoxia.Evofosfamide (TH
302) induced DNA-damage and a dose-dependent antiproliferative response in A549
cells on cellular pretreatment under hypoxia, and supra-additively reduced
clonogenic survival in combination with IR. Concomitant treatment of A549-derived
tumor xenografts with evofosfamide and fractionated irradiation induced the
strongest treatment response in comparison to the corresponding neoadjuvant and
adjuvant regimens. Adjuvant evofosfamide was more potent than concomitant and
neoadjuvant evofosfamide when combined with a single high dose of IR. Hypoxic UT
SCC-14 cells and tumor xenografts thereof were resistant to evofosfamide alone
and in combination with IR, most probably due to reduced P450 oxidoreductase
expression, which might act as major predictive determinant of sensitivity to
HAPs.In conclusion, evofosfamide with IR is a potent combined treatment modality
against hypoxic tumors. However, the efficacy and the therapeutic outcome of this
combined treatment modality is, as indicated here in preclinical tumor models,
dependent on scheduling parameters and tumor type, which is most probably related
to the status of respective HAP-activating oxidoreductases. Further biomarker
development is necessary for the launch of successful clinical trials.
PMID- 28423595
TI - dUTPase inhibition augments replication defects of 5-Fluorouracil.
AB - The antimetabolite 5-Fluorouracil (5-FU) is used in the treatment of various
forms of cancer and has a complex mode of action. Despite 6 decades in clinical
application the contribution of 5-FdUTP and dUTP [(5-F)dUTP] and 5-FUTP
misincorporation into DNA and RNA respectively, for 5-FU-induced toxicity is
still under debate.This study investigates DNA replication defects induced by 5
FU treatment and how (5-F)dUTP accumulation contributes to this effect. We reveal
that 5-FU treatment leads to extensive problems in DNA replication fork
progression, causing accumulation of cells in S-phase, DNA damage and ultimately
cell death. Interestingly, these effects can be reinforced by either depletion or
inhibition of the deoxyuridine triphosphatase (dUTPase, also known as DUT),
highlighting the importance of (5-F)dUTP accumulation for cytotoxicity.With this
study, we not only extend the current understanding of the mechanism of action of
5-FU, but also contribute to the characterization of dUTPase inhibitors. We
demonstrate that pharmacological inhibition of dUTPase is a promising approach
that may improve the efficacy of 5-FU treatment in the clinic.
PMID- 28423596
TI - Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus
replication and enhances anti-apoptotic signaling responses.
AB - Viral infection activates a host's cellular phosphatidylinositol 3-kinase
(PI3K)/Akt signaling pathway, which is involved in cell differentiation, growth,
survival, and apoptosis. To elucidate molecular mechanisms in the pathogenesis of
Newcastle disease virus (NDV), we demonstrated that NDV transiently activates the
PI3K/Akt pathway in chicken cells at an early phase of infection. Its activation
was observed as early as 15 min post-infection and gradually weakened after 24 h.
Incubating cells with a PI3K inhibitor, LY294002 or wortmannin, prior to NDV
infection decreased NDV progeny yields and suppressed Akt phosphorylation at
early times post-infection. Akt activation is triggered by NDV-GM or NDV-F48E9
and is abolished by methyl beta-cyclodextrin and chlorpromazine. Treatment
following NDV-La Sota infection had no obvious effect. However, inhibiting PI3K
activation promoted apoptotic responses during an early stage of NDV infection.
The pan caspase inhibitor ZVAD-FMK mitigated the reduction in Akt phosphorylation
by inhibiting PI3K activation, which indicates the signaling pathway promotes
cell survival and, in turn, facilitates viral replication. By suppressing
premature apoptosis upon NDV infection, the PI3K/Akt pathway enhances the anti
apoptotic response.
PMID- 28423597
TI - HRD1 sensitizes breast cancer cells to Tamoxifen by promoting S100A8 degradation.
AB - Estrogen receptor alpha positive (ER+) of breast cancer could develop resistance
to antiestrogens including Tamoxifen. Our previous study showed that the E3
ubiquitin ligase HRD1 played an important role in anti-breast cancer. However,
its role in chemotherapy resistance hasn't been reported. In this study, we found
that HRD1 expression was downregulated in Tamoxifen-resistant breast cancer cell
line MCF7/Tam compared to the Tamoxifen sensitive cell line MCF7. Moreover,
S100A8 is the direct target of HRD1 by proteome analysis. Our data showed that
HRD1 decreased the protein level of S100A8 through ubiquitination while HRD1 was
regulated by acetylation of histone. More importantly, HRD1 knockdown
significantly increased the cell survival of MCF7 cells to the Tamoxifen
treatment. HRD1 overexpression sensitized MCF7/Tam cells to the Tamoxifen
treatment in vitro and in vivo. In conclusion, the decrease of HRD1 expression
contributed to Tamoxifen resistance in breast cancer.
PMID- 28423598
TI - Next generation mapping reveals novel large genomic rearrangements in prostate
cancer.
AB - Complex genomic rearrangements are common molecular events driving prostate
carcinogenesis. Clinical significance, however, has yet to be fully elucidated.
Detecting the full range and subtypes of large structural variants (SVs), greater
than one kilobase in length, is challenging using clinically feasible next
generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new
technology that allows for the interrogation of megabase length DNA molecules
outside the detection range of single-base resolution NGS. In this study, we
sought to determine the feasibility of using the Irys (Bionano Genomics Inc.)
nanochannel NGM technology to generate whole genome maps of a primary prostate
tumor and matched blood from a Gleason score 7 (4 + 3), ETS-fusion negative
prostate cancer patient. With an effective mapped coverage of 35X and sequence
coverage of 60X, and an estimated 43% tumor purity, we identified 85 large
somatic structural rearrangements and 6,172 smaller somatic variants,
respectively. The vast majority of the large SVs (89%), of which 73% are
insertions, were not detectable ab initio using high-coverage short-read NGS.
However, guided manual inspection of single NGS reads and de novo assembled
scaffolds of NGM-derived candidate regions allowed for confirmation of 94% of
these large SVs, with over a third impacting genes with oncogenic potential. From
this single-patient study, the first cancer study to integrate NGS and NGM data,
we hypothesise that there exists a novel spectrum of large genomic rearrangements
in prostate cancer, that these large genomic rearrangements are likely early
events in tumorigenesis, and they have potential to enhance taxonomy.
PMID- 28423599
TI - Re-expression of miR-200c suppresses proliferation, colony formation and in vivo
tumor growth of murine claudin-low mammary tumor cells.
AB - Claudin-low breast cancer is a relatively rare breast cancer subtype. These
cancers are typically ER-/PR-/HER2- and express high levels of mesenchymal genes
as well as genes associated with inflammation, angiogenesis and stem cell
function. In addition to alterations in gene expression, it was recently
demonstrated that claudin-low breast cancers express very low levels of the miR
200 family of miRNAs. Given that each miRNA can regulate tens, hundreds or even
thousands of genes, miRNAs are being evaluated as therapeutic targets. In this
study we show that mammary tumors from MTB-IGFIR transgenic mice and cell lines
derived from these tumors represent a model of human claudin-low breast cancer
and murine claudin-low mammary tumors and cell lines express only very low levels
of all five members of the miR-200 family. Reduced miR-200 family expression
appears to be regulated via methylation as cells and tumors expressing low levels
of miR-200 family members had higher levels of CpG methylation in a putative
promoter region than tumors and cells expressing high levels of miR-200 family
members. Re-expression of miR-200c in murine claudin-low mammary tumor cells
inhibited tumor cell proliferation and colony formation in vitro and tumor growth
in vivo. With respect to tumor growth in vivo, re-expression of miR-200c was
associated with a reduction in tumor vasculature and expression of Flt1 and
Vegfc. Therefore, miR-200c is an important regulator of mesenchymal tumor cell
growth.
PMID- 28423600
TI - Systematic screening of isogenic cancer cells identifies DUSP6 as context
specific synthetic lethal target in melanoma.
AB - Next-generation sequencing has dramatically increased genome-wide profiling
options and conceptually initiates the possibility for personalized cancer
therapy. State-of-the-art sequencing studies yield large candidate gene sets
comprising dozens or hundreds of mutated genes. However, few technologies are
available for the systematic downstream evaluation of these results to identify
novel starting points of future cancer therapies.We improved and extended a site
specific recombination-based system for systematic analysis of the individual
functions of a large number of candidate genes. This was facilitated by a novel
system for the construction of isogenic constitutive and inducible gain- and loss
of-function cell lines. Additionally, we demonstrate the construction of isogenic
cell lines with combinations of the traits for advanced functional in vitro
analyses. In a proof-of-concept experiment, a library of 108 isogenic melanoma
cell lines was constructed and 8 genes were identified that significantly reduced
viability in a discovery screen and in an independent validation screen. Here, we
demonstrate the broad applicability of this recombination-based method and we
proved its potential to identify new drug targets via the identification of the
tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell
lines with BRAF V600E mutations and high DUSP6 expression.
PMID- 28423601
TI - A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity.
AB - The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), many
of which are emerging as critical regulators of cell fate. However, their
functions as well as their transcriptional regulation are only partially
understood. The E2F1 transcription factor induces both proliferation and
apoptosis, and is a critical downstream target of the tumor suppressor, RB. Here,
we provide evidence that a novel lncRNA named GASL1 is transcriptionally
regulated by E2F1; GASL1 levels are elevated upon activation of exogenous E2F1 or
endogenous E2Fs. Inhibition of GASL1 expression induced cell cycle progression,
and in particular, G1 exit. Moreover, GASL1 silencing enhanced cell
proliferation, while, conversely, its ectopic expression inhibited proliferation.
Knockdown of GASL1 also enhanced E2F1-induced apoptosis, suggesting the existence
of an E2F/GASL1 negative feedback loop. In agreement with this notion, silencing
of GASL1 led to increased levels of phosphorylated pRB and loss of Rb impaired
the effect of GASL1 silencing on G1 exit. Importantly, xenograft experiments
demonstrated that GASL1 deletion enhances tumor growth. Moreover, low levels of
GASL1 are associated with decreased survival of liver cancer patients. Taken
together, our data identify GASL1 as a novel lncRNA regulator of cell cycle
progression and cell proliferation with a potential role in cancer.
PMID- 28423602
TI - Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients
with urothelial carcinoma.
AB - Galectine-4 (gal-4), encoded by the LGALS4 gene, was recently shown to exhibit a
tumor suppressive effect in colorectal carcinoma and pancreatic adenocarcinoma,
although how the expression of this gene is regulated remains unknown. No reports
describe the significance of gal-4 in the malignant potential of urothelial
tumors. Thus, we analyzed LGALS4 methylation and gene expression and their
clinical relevance and biological function in urothelial carcinoma (UC). LGALS4
methylation was initially identified as a progression biomarker for UC patients
through genome-wide DNA methylation profiling of 16 tumor samples. Bisulfite
sequencing PCR and immunohistochemistry were performed to validate the promoter
methylation and expression of LGALS4. We used quantitative methylation-specific
PCR to determine the methylation levels of LGALS4 normalized to ACTB in the tumor
samples of 79 UC patients and compared the levels between patients with different
clinicopathological characteristics. The association with survival probability
was analyzed with the Kaplan-Meier method and Cox regression analysis. The
ectopic expression of gal-4 in cancer cell lines was used to address its
biological function in UC in vitro. The promoter hypermethylation of LGALS4
(>2.51, log10 scale) revealed a positive correlation with high levels of both
histological grade and tumor T category and with lymph node metastasis (all
P<=0.001). In addition, LGALS4 hypermethylation was an independent predictor of
inferior survival in UC patients (P<0.05). The ectopic expression studies
demonstrated that gal-4 suppressed urothelial cancer cell growth, migration, and
invasion. Thus, LGALS4 may function as a tumor suppressor gene in UC progression.
Our findings provide evidence that methylation-mediated LGALS4 gene repression
may be involved in urothelial tumor progression.
PMID- 28423603
TI - Adipose-derived mesenchymal stem cells promote osteosarcoma proliferation and
metastasis by activating the STAT3 pathway.
AB - Osteosarcoma is the most common primary bone malignancy in children and young
adults, but the role of adipose-derived mesenchymal stem cells (ADSCs) in the
rapid progression of osteosarcoma is still unclear. Here, we found that ADSCs
promoted tumour growth and invasion by increasing matrix metalloproteinase 2/9
(MMP2/9) expression in tumour cells. The persistent activation of signal
transducer and activator of transcription 3 (STAT3) has been shown to directly
promote tumour growth by mediating a wide spectrum of cellular responses, and
STAT3 activation was detected in osteosarcoma cells co-cultured with ADSCs or
treated with ADSC-conditioned medium. Furthermore, siRNA-mediated STAT3
inhibition in osteosarcoma cells decreased cell proliferation and invasion and
down-regulated MMP2/9 expression. In addition, a nude mouse model of osteosarcoma
was established by injecting luciferase-labelled MG63 cells into the tibia. As
shown in in vivo bioluminescence images, ADSCs promoted tumour cell
proliferation, invasion progression and metastasis. STAT3 inhibition attenuated
tumour growth and metastasis and prolonged the survival of these mice. After the
siRNA treatment, the MMP2, MMP9 and Ki67 levels decreased. Based on these data,
stromal ADSCs promote osteosarcoma progression by increasing STAT3 signalling
mediated MMP2/9 expression.
PMID- 28423604
TI - Clinicopathologic and prognostic characteristics of alpha-fetoprotein-producing
gastric cancer.
AB - Alpha-fetoprotein-producing gastric cancer (AFPGC) accounts for 1.5%-7.1% of all
gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more
aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor
prognosis. To improve understanding of AFPGC we reviewed a consecutive series of
82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC
among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed
with metastasis at the time of presentation, mainly liver metastasis. The serum
AFP level of patients with AFPGC was significantly associated with tumor
differentiation. Histologically, these AFPGC patients were composed of 34.55%
hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like
type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren
classification, and number of metastatic lymph nodes showed significant
differences among these four subtypes. The overall survival time was 42.02 months
and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee
on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and
surgery were prognostic factors for overall survival; however, TNM stage was the
only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare,
unique, and heterogeneous entity, and its proper identification and treatment
remain a challenge. More attention should be paid to AFPGC to improve patient
care and the dismal prognosis.
PMID- 28423605
TI - Pregnancy at early age is associated with a reduction of progesterone-responsive
cells and epithelial Wnt signaling in human breast tissue.
AB - BACKGROUND: Pregnancy at early age is the most significant modifiable factor
which consistently decreases lifetime breast cancer risk. However, the underlying
mechanisms haven't been conclusively identified. Studies in mice suggest a
reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a
downregulation of the Wnt signaling pathway as being one of the main mechanisms
for the protective effect of early pregnancy. The aim of our study was to
validate these findings in humans. METHODS: We collected benign breast tissue of
125 women who had been stratified according to age at first pregnancy and the
occurrence of subsequent breast cancer, and performed immunohistochemistry for
PR, Wnt4 and the Wnt-target Versican. RESULTS: The number of PR positive
epithelial cells was significantly lower in the group of women with early
pregnancy and no subsequent breast cancer compared to the group of nulliparous
women with subsequent invasive breast cancer (p = 0.0135). In women with early
pregnancy, expression of Versican and Wnt4 was significantly lower compared to
nulliparous women (p = 0.0036 and p = 0.0241 respectively), and Versican
expression was also significant lower compared to women with late pregnancy (p <
0.0001). DISCUSSION: Our results confirm prior observations in mice and suggest a
role of downregulation of epithelial Wnt signaling in the protective effect of
early pregnancy in humans. This results in a decreased proliferation of
stem/progenitor cells; therefore, the Wnt signaling pathway may represent a
potential target for breast cancer prevention in humans.
PMID- 28423607
TI - Cancer and neurodegeneration: two sides, same coin?
PMID- 28423606
TI - Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the
dependence receptor EphA4.
AB - EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR)
by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as
conditional tumor suppressors, engaging cell death based on ligand availability;
this mechanism is bypassed by overexpression of DRs ligands in some aggressive
cancers. The pair EphA4/Ephrin-B3 favors survival of neuronal progenitors of the
brain subventricular zone, an area where glioblastoma multiform (GBM) are thought
to originate. Here, we report that Ephrin-B3 is highly expressed in human
biopsies and that it inhibits EphA4 pro-apoptotic activity in tumor cells.
Angiogenesis is directly correlated with GBM aggressiveness and we demonstrate
that Ephrin-B3 also supports the survival of endothelial cells in vitro and in
vivo. Lastly, silencing of Ephrin-B3 decreases tumor vascularization and growth
in a xenograft mice model. Interference with EphA4/Ephrin-B3 interaction could
then be envisaged as a relevant strategy to slow GBM growth by enhancing EphA4
induced cell death.
PMID- 28423609
TI - Glial phenotype modulators.
PMID- 28423608
TI - Anthracyclines suppress pheochromocytoma cell characteristics, including
metastasis, through inhibition of the hypoxia signaling pathway.
AB - Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine
tumors derived from adrenal or extra-adrenal chromaffin cells, respectively.
Metastases are discovered in 3-36% of patients at the time of diagnosis.
Currently, only suboptimal treatment options exist. Therefore, new therapeutic
compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we
investigated if anthracyclines were able to suppress the progression of
metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells
using in vitro and in vivo models, and demonstrated that anthracyclines,
particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the
binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia
response element (HRE) sites on DNA. This resulted in reduced transcriptional
activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate
kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate
dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which
consequently inhibited the growth of metastatic PHEO. Additionally, IDA
downregulated hypoxia signaling by interfering with the transcriptional
activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the
dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our
results indicate that anthracyclines are prospective candidates for inclusion in
metastatic PHEO/PGL therapy, especially in patients with gene mutations involved
in the hypoxia signaling pathway.
PMID- 28423610
TI - Targeting glutamate transporter-1 in neurological diseases.
PMID- 28423612
TI - Correction: Nebivolol, a beta1-adrenergic blocker, protects from peritoneal
membrane damage induced during peritoneal dialysis.
PMID- 28423611
TI - The stem cell/cancer stem cell marker ALDH1A3 regulates the expression of the
survival factor tissue transglutaminase, in mesenchymal glioma stem cells.
AB - Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and
acyltransferase activities, has been implicated in the survival and chemotherapy
resistance of aggressive cancer cells and cancer stem cells, including glioma
stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs
referred to as proneural (PN) and mesenchymal (MES), we find that the
phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively
express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and
survival of these cells was sensitive to treatment with tTG inhibitors, with a
benefit being observed when combined with the standard of care for high grade
gliomas (i.e. radiation or temozolomide). Efforts to understand the molecular
drivers of tTG expression in MES GSCs revealed an unexpected link between tTG and
a common marker for stem cells and cancer stem cells, Aldehyde dehydrogenase 1A3
(ALDH1A3). ALDH1A3, as well as other members of the ALDH1 subfamily, can function
in cells as a retinaldehyde dehydrogenase to generate retinoic acid (RA) from
retinal. We show that the enzymatic activity of ALDH1A3 and its product, RA, are
necessary for the observed expression of tTG in MES GSCs. Additionally, the
ectopic expression of ALDH1A3 in PN GSCs is sufficient to induce the expression
of tTG in these cells, further demonstrating a causal link between ALDH1A3 and
tTG. Together, these findings ascribe a novel function for ALDH1A3 in an
aggressive GSC phenotype via the up-regulation of tTG, and suggest the potential
for a similar role by ALDH1 family members across cancer types.
PMID- 28423613
TI - Secreted GRP78 activates EGFR-SRC-STAT3 signaling and confers the resistance to
sorafeinib in HCC cells.
AB - Acquired resistance is a common phenomenon for HCC patients who undergone
sorafenib treatment, however the mechanism by which acquired resistance develops
remains elusive. In this study, we found that GRP78 could be detected in the
serum samples of HCC patients and the conditional medium of multiple HCC cell
lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed
that secreted GRP78 facilitated the proliferation and inhibited the apoptosis
induced by sorafenib both in HCC cell lines and in tumor xenografts. We further
found that secreted GRP78 could interact physically with EGFR, therefore
activates EGFR signaling pathway. knockdown of EGFR decreased secreted GRP78
induced phosphorylation of SRC and STAT3. By contrast, overexpression of EGFR
further enhanced the phosphorylation of SRC and STAT3 induced by secreted GRP78,
suggesting the critical role of EGFR in secreted GRP78 conferred resistance to
sorafeinib. Moreover, inhibition of SRC by PP2 antagonized the resistance to
sorafenib and inhibited the activation of STAT3 conferred by secreted GRP78.
Taken together, our results showed that secreted GRP78 could interact with EGFR,
activate EGFR-SRC-STAT3 signaling, conferring the resistance to sorafenib.
PMID- 28423614
TI - Marriage is a dependent risk factor for mortality of colon adenocarcinoma without
a time-varying effect.
AB - BACKGROUND: It has been well recognized that the effects of many prognostic
factors could change during long-term follow-up. Although marriage has been
proven to be a significant prognostic factor for the survival of colon cancer,
whether the effect of marriage is constant with time remain unknown. This study
analyzed the impact of marital status on the mortality of colon cancer patients
with an extended Cox model that allowed for time-varying effects. METHODS: We
identified 71,955 patients who underwent colectomy between 2004 and 2009 to treat
colon adenocarcinoma from the Surveilance, Epidemiology and End Results Database.
The multivariate extended Cox model was used to evaluate the effect of marital
status on all-cause mortality, while the Fine-Gray competing risks model was used
for colon cancer-specific mortality, with death from other causes as the
competing risk. RESULTS: The unmarried patients carried a 1.37-fold increased
risk of all-cause mortality compared with the married patients (95%CI: 1.33-1.40;
p<0.001), and the hazard ratio remained constant over time. Being unmarried was
at a higher risk of death from colon adenocarcinoma as well as death from other
causes. Four variables including tumor site, tumor grade, sex and TNM stage were
proved to have time-varying effects on survival. CONCLUSIONS: Marriage is a
dependent prognosis factor for survival of surgically treated colon
adenocarcinoma patients. Psychological interventions are suggested to improve
receipt of treatment among unmarried patients, as their poor survival may be due
to the inefficient treatment.
PMID- 28423615
TI - EXOC3L2 rs597668 variant contributes to Alzheimer's disease susceptibility in
Asian population.
AB - Recent genome-wide association studies have established the association between
EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population.
However, recent studies reported inconsistent results in Asian population. Here,
we performed a systematic review and meta-analysis to evaluate the impact of
rs597668 on AD risk in Asian population using a total of 8686 samples including
2855 cases and 5831 controls. Meanwhile, we selected 17,008 AD cases and 37,154
controls in European population to evaluate the potential heterogeneity between
East Asian and European populations. In East Asian population, we identified no
potential heterogeneity with P=0.31 and I2 = 15.8%. By meta-analysis, we
identified positive association between rs597668 and AD risk with P=0.023,
OR=0.93, 95% CI 0.87-0.99. We further found significant heterogeneity in pooled
Asian and European populations with P<0.0001 and I2 = 87.7%. The meta-analysis
indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11. In
summary, all these findings indicate that rs597668 C allele is a risk factor for
AD in European population with OR=1.18 and P=2.49E-13. However the rs597668 C
allele played a protective role in AD with OR=0.93 and P=0.023 in East Asian
population.
PMID- 28423616
TI - Suppression of microRNA-16 protects against acute myocardial infarction by
reversing beta2-adrenergic receptor down-regulation in rats.
AB - microRNA-16 (miR-16) has been shown to be up-regulated in ischemic heart. Beta2
adrenoreceptor (beta2-AR) exerts cardioprotective property in ischemic injury.
This study aims to determine the effect of miR-16 in cardiac injury in rats and
the possible involvement of beta2-AR in this process. Acute myocardial infarction
(AMI) model in rats was induced by ligation of left coronary artery. Neonatal rat
ventricular cells (NRVCs) were cultured in vitro tests. The cardiomyocyte model
of oxidative injury was mimicked by hydrogen peroxide. The expression of miR-16
was obviously up-regulated and beta2-AR was remarkably down-regulated in both AMI
rats and NRVCs under oxidative stress. miR-16 over-expression in NRVCs reduced
cell viability and increased apoptosis. Conversely, inhibition of endogenous miR
16 with its specific inhibitor reversed these changes. Over-expression of miR-16
using an miR-16 lentivirus in AMI rats markedly increased cardiac infarct area,
lactate dehydrogenase and creatine kinase activity, and exacerbated cardiac
dysfunction. Lentivirus-mediated knockdown of miR-16 alleviated acute cardiac
injury. Moreover, miR-16 over-expression significantly suppressed beta2-AR
protein expression in both cultured NRVCs and AMI rats, while inhibition of miR
16 displayed opposite effect on beta2-AR protein expression. Luciferase assay
confirmed that miR-16 could directly target the 3'untranslated region of beta2-AR
mRNA. miR-16 is detrimental to the infarct heart and suppression of miR-16
protects rat hearts from ischemic injury via up-regulating of beta2-AR by binding
to the 3'untranslated region of beta2-AR gene. This study indicates that
targeting miR-16/beta2-AR axis may be a promising strategy for ischemic heart
disease.
PMID- 28423617
TI - The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates
pancreatic cancer.
AB - AIM: To determine the regulation and function of the neural precursor cell
expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to
determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT
signaling. METHODS: We investigated the expression of NEDD4 and the tumor
suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line
and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether
RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and
migration. We subsequently determined the crosstalk between NEDD4 expression and
the PTEN/PI3K/AKT signaling pathway. Finally, we determined the mechanism behind
differential NEDD4 protein expression in pancreatic cancer. RESULTS: The
expression of NEDD4 was heterogeneous in PDAC cells, but was significantly higher
compared to normal pancreatic ductal epithelial cells. Analogically, PTEN was
decreased in the PDAC cells. A combination of MTT assay, wound healing migration
assay, and transwell invasion assays confirmed that depletion of NEDD4 decreased
the proliferation and migration ability of PDAC cells. Western blot and
immunofluorescence results revealed that NEDD4 could affect PTEN/PI3K/AKT
signaling pathway in PDAC cells. Polysomal profiling revealed that higher NEDD4
protein expression in PDAC cells was due to undefined mechanism involving
translational activation. CONCLUSIONS: Our results reveal a novel mechanism of
upregulation of NEDD4 expression in PDAC. Our findings indicate that NEDD4
potentially plays a critical role in activating the PI3K/AKT signaling pathway by
negatively regulating PTEN levels in PDAC cells, which promotes pancreatic cancer
cell proliferation and metastasis. Therefore, NEDD4 may be a potential
therapeutic target in PDAC.
PMID- 28423618
TI - miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma.
AB - Increasing evidence suggests that microRNAs play key roles in lung cancer. Our
previous study demonstrated that microRNA 363-3p (miR-363-3p) is downregulated in
lung cancer tissues. In this study, we demonstrated that overexpression of miR
363-3p inhibits the proliferation and colony formation of A549 and H441 cells,
while silencing of miR-363-3p has the converse effects. The anti-oncogenic
function of miR-363-3p was verified in a mouse tumor xenograft model.
Furthermore, cell cycle analysis showed miR-363-3p can induce S phase arrest by
downregulating Cyclin-D1 and upregulating Cyclin-dependent kinase-2 in lung
adenocarcinoma cells. Additionally, miR-363-3p enhances cell apoptosis, whereas
miR-363-3p inhibitor prevents apoptosis and leads to downregulation of Bax and
Bak expression. The anti-proliferative function of miR-363-3p toward lung cancer
cells may be explained by its ability to inhibit the activation of the mTOR and
ERK signaling pathways. Using target prediction software and luciferase reporter
assays, we identified PCNA as a specific target of miR-363-3p. miR-363-3p can
decreased the accumulation of endogenous PCNA in lung adenocarcinoma cells.
Moreover, exogenous expression of PCNA relieve the inhibition of miR-363-3p on
cell proliferation, colony formation and mTOR and ERK signaling pathways. Taken
together, our data indicate that miR-363-3p suppresses tumor growth by targeting
PCNA in lung adenocarcinoma.
PMID- 28423619
TI - CDCA2 promotes lung adenocarcinoma cell proliferation and predicts poor survival
in lung adenocarcinoma patients.
AB - Cell division cycle associated 2(CDCA2) is overexpressed in neuroblastoma and
oral squamous cell carcinoma, and its overexpression positively correlates to
tumor progression. However, the biological and clinical significance of CDCA2 in
lung adenocarcinoma(LAC) has never been investigated. We determined the
expression profile and clinical significance of CDCA2 using The Cancer Genome
Atlas(TCGA) and tissue microarray(TMA). Furthermore, we explored the biological
function of CDCA2 both in vitro and in vivo. A great upregulation of CDCA2 was
observed in LAC tissues compared with adjacent normal tissues. Importantly, Cox
regression analysis indicated that high level of CDCA2 was an independent risk
factor for overall survival(OS) in LAC patients (TCGA: HR = 1.720, p = 0.004;
TMA: HR = 1.971, p = 0.023). Inhibition of CDCA2 suppressed the proliferation of
LAC cells via G1 phase arrest by downregulating cyclin E1(CCNE1), while
overexpression of CDCA2 promoted LAC cells proliferation by upregulating CCNE1.
Moreover, the oncogenic activity of CDCA2 was also confirmed in vivo. In
conclusion, CDCA2 promotes proliferation of LAC cells and predicts poor prognosis
in LAC patients. CDCA2 might play a significant role in LAC progression.
PMID- 28423620
TI - Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a
possible role for exosomal disposal of tumor suppressor miRNAs.
AB - Exosomes have emerged as important mediators of diverse biological functions
including tumor suppression, tumor progression, invasion, immune escape and cell
to-cell communication, through the release of molecules such as mRNAs, miRNAs,
and proteins. Here, we identified differentially expressed exosomal miRNAs
between normal epithelial ovarian cell line and both resistant and sensitive
ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from
SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is
associated with better survival in patients with ovarian serous
cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony
formation, invasion, and migration and triggered G0/G1 cell cycle arrest and
apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth
in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly
targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein
levels. Following this inhibition, the expression of proteins downstream of SRC,
such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest
that OC cells secrete the tumor-suppressive miR-940 into the extracellular
environment via exosomes, to maintain their invasiveness and tumorigenic
phenotype.
PMID- 28423621
TI - Epstein-Barr virus encoded microRNA BART7 regulates radiation sensitivity of
nasopharyngeal carcinoma.
AB - Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very
sensitive to radiotherapy. To date, the underlying mechanism remains poorly
understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7
(ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by
targeting GFPT1/TGFbeta1 signaling. GFPT1 is the the key rate-limiting enzyme of
the hexosamine signaling pathway and governs TGFbeta1 production. TGFbeta1, a
pleotropic cytokine with the potency to trigger self-renewal and damage-repair
machinery in somatic cells. TGFbeta1 can protect zebrafish embryo from the lethal
effects of radiation treatment. In silico analysis showed that ebv-miR-BART7
could target GFPT1 transcript. Correlation analysis on primary NPC tissues
suggested that ebv-miR-BART7 and GFPT1 have negative expression correlation.
Expression of GFPT1 and TGFbeta1 were inducible by radiation in NPC cell with ebv
miR-BART7 expression. Further, suppressing endogenous GFPT1 expression inhibited
TGFbeta1 which subsequently increased the responsiveness of NPC to radiation
treatment. Taken together, our results demonstrated that ebv-miR-BART7 controls
TGFbeta1 production by targeting GFPT1. Detection of ebv-miR-BART7 may provide
useful indicator for monitoring NPC progression and predict therapeutic outcomes.
PMID- 28423622
TI - HnRNPK/miR-223/FBXW7 feedback cascade promotes pancreatic cancer cell growth and
invasion.
AB - Several studies have identified miR-223 critically involved in various types of
cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action
and regulatory mechanisms in PDAC remains largely unclear. In this study, we
found that the expression levels of miR-223 were increased in clinical samples
with PDAC (81.6%). The upregulation of miR-223 increases the proliferation,
migration, and invasive abilities of PDAC cells in vitro and in vivo.
Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7
reverted miR-223- induced drastic proliferation in PDAC cells. Interestingly, miR
223 promoter was found to form a coprecipitable complex with hnRNPK, and siRNA
knockdown of hnRNPK in PDAC cells reduced the levels of miR-223. These results
show that hnRNPK is a cellular protein that binds and affects the accumulation of
miR-223 in PDAC. Furthermore, FBXW7 interacts with hnRNPK and promotes its
degradation, which requires phosphorylation of hnRNPK at threonine 1695 by GSK3.
Consistently, we observed an inverse expression pattern between FBXW7 and miR
223, whereas a positive expression pattern between miR-223 and hnRNPK was found
in human PDAC tissues. These data unveiled an important new miR-223/FBXW7/HnRNPK
feedback cascade in human PDAC.
PMID- 28423623
TI - Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell
mediated killing through matrix-metalloproteinases secretion.
AB - Cancer-associated fibroblasts (CAFs) play a central role in the complex process
of tumor-stroma interaction and promote tumor growth. Emerging evidences also
suggest that these fibroblasts are involved in the alteration of the anti-tumor
immune response by impacting several immune cell populations, especially through
their secretion of pro-inflammatory and immunosuppressive factors in the tumor
microenvironment. However, the underlying immuno-modulating mechanisms triggered
by these fibroblasts are still only partially defined. In this study, we provide
evidence that melanoma-associated fibroblasts decrease the susceptibility of
melanoma tumor cells to NK-mediated lysis through the secretion of active matrix
metalloproteinases. This secretion reduces the expression of the two NKG2D
ligands, MICA/B, at the surface of tumor cells and consequently decreases the
NKG2D-dependent cytotoxic activity of NK cells against melanoma tumor cells.
Together, our data demonstrate that the modification of tumor cell susceptibility
to killer cells is an important determinant of the anti-tumor immune response
alteration triggered by CAFs.
PMID- 28423624
TI - Assessment of female breast dose for thoracic cone-beam CT using MOSFET
dosimeters.
AB - OBJECTIVE: To assess the breast dose during a routine thoracic cone-beam CT
(CBCT) check with the efforts to explore the possible dose reduction strategy.
MATERIALS AND METHODS: Metal oxide semiconductor field-effect transistor (MOSFET)
dosimeters were used to measure breast surface doses during a thorax kV CBCT scan
in an anthropomorphic phantom. Breast doses for different scanning protocols and
breast sizes were compared. Dose reduction was attempted by using partial arc
CBCT scan with bowtie filter. The impact of this dose reduction strategy on image
registration accuracy was investigated. RESULTS: The average breast surface doses
were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with
filtration, respectively. This indicates a dose reduction of 41.8% by use of
bowtie filter. It was found 220 degrees partial arc scanning significantly
reduced the dose to contralateral breast (44.4% lower than ipsilateral breast),
while the image registration accuracy was not compromised. CONCLUSIONS: Breast
dose reduction can be achieved by using ipsilateral 220 degrees partial arc scan
with bowtie filter. This strategy also provides sufficient image quality for
thorax image registration in daily patient positioning verification.
PMID- 28423625
TI - Inhibition activity of a disulfide-stabilized diabody against basic fibroblast
growth factor in lung cancer.
AB - The over-expression of basic fibroblast growth factor (bFGF) plays a crucial role
in the development, invasion and metastasis of lung cancer. Therefore,
neutralizing antibodies against bFGF may inhibit the growth of lung cancer. In
this study, a Disulfide-stabilized diabody (ds-Diabody) against bFGF was
constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the
position of VH44 and VL100 in the scFv. The ds-Diabody was constructed and
expressed in Pichia pastoris. We found that the ds-Diabody against bFGF could
efficiently suppress the proliferation, migration and invasion of human lung
cancer A549 cells in vitro. Moreover, in A549 cells, the ds-Diabody against bFGF
could inhibit bFGF-induced activation of downstream signaling regulators, such as
phospho-Akt and phospho-MAPK. In the nude mouse xenograft model of lung cancer,
the ds-Diabody against bFGF could significantly inhibit tumor growth and decrease
the densities of micro-vessels and lymphatic vessels in tumor tissue. Our data
indicate that the ds-Diabody against bFGF could effectively suppress the lung
cancer growth through blockade of bFGF signaling pathway and inhibition of tumor
angiogenesis, which may make it a potential therapeutic candidate antibody drug
for human lung cancer therapy.
PMID- 28423627
TI - Platelet distribution width correlates with prognosis of gastric cancer.
AB - BACKGROUND: Activated platelets promote tumor cell growth, aberrant angiogenesis,
and invasion. However, the value of platelet indices for predicting survival in
gastric cancer remains unknown. The goal of this study was to investigate the
predictive significance of platelet indices in gastric cancer. RESULT: Reduced
platelet distribution width (PDW) was significantly correlated with age,
carcinoembryonic antigen, tumor stage, nodule stage, and tumor-nodule-metastases
stage. Moreover, decreased PDW correlated with a shorter overall survival in
gastric cancer. Multivariate analysis identified PDW as an independent prognostic
factor for overall survival (hazard ratio: 0.493, 95% confidence interval: 0.319
0.761, p = 0.001). METHOD: A total of 294 patients with gastric cancer were
retrospectively analyzed between January 2009 and December 2009. The association
between platelet indices and overall survival were evaluated. The prognostic
analysis was carried out with Cox regression model. CONCLUSION: PDW is easily
available with routine blood counts. Our data revealed that reduced PDW is
unfavorable prognostic factor in gastric cancer. Further studies are warranted.
PMID- 28423626
TI - Prognostic value of loss of heterozygosity and sub-cellular localization of SMAD4
varies with tumor stage in colorectal cancer.
AB - BACKGROUND: Although loss of heterozygosity (LOH) at chromosome location 18q21
and decreased expression of SMAD4 in invasive colorectal cancers (CRCs) correlate
with poor patient survival, the prognostic value of LOH at 18q21 and sub-cellular
localization of SMAD4 have not been evaluated in relation to tumor stage.
METHODS: Genomic DNA samples from 209 formalin-fixed, paraffin-embedded sporadic
CRC tissues and their matching controls were analyzed for 18q21 LOH, and
corresponding tissue sections were evaluated by immunohistochemistry for
expression of SMAD4 and assessed for its sub-cellular localization (nuclear vs.
cytoplasmic). In addition, 53 frozen CRCs and their matching control tissues were
analyzed for their mutational status and mRNA expression of SMAD4. The phenotypic
expression pattern and LOH status were evaluated for correlation with patient
survival by the use of Kaplan-Meier and Cox regression models. RESULTS: LOH of
18q21 was detected in 61% of the informative cases. In 8% of the cases, missense
point mutations were detected in Smad4. In CRCs, relative to controls, there was
increased SMAD4 staining in the cytoplasm (74%) and decreased staining in the
nuclei (37%). LOH of 18q21 and high cytoplasmic localization of SMAD4 were
associated with shortened overall survival of Stage II patients, whereas low
nuclear expression of SMAD4 was associated with worse survival, but only for
patients with Stage III CRCs. CONCLUSIONS: LOH of 18q21 and high cytoplasmic
localization of SMAD4 in Stage II CRCs and low nuclear SMAD4 in Stage III CRCs
are predictors of shortened patient survival.
PMID- 28423628
TI - Benzyl isothiocyanate induces reactive oxygen species-initiated autophagy and
apoptosis in human prostate cancer cells.
AB - Benzyl isothiocyanate (BITC) in cruciferous plants, which are part of the human
diet, has been shown to induce apoptosis in various types of cancer. In this
study, we show that BITC effectively suppresses the growth of cultured human
prostate cancer cells (CRW-22Rv1 and PC3) by causing mitochondrial membrane
potential loss, caspase 3/7 activation and DNA fragmentation. Furthermore, BITC
induces ROS generation in these cells. The induction of apoptosis by BITC was
significantly attenuated in the presence of N-acetylcysteine (NAC) and catalase
(CAT), well-studied ROS scavengers. The induction of autophagy in BITC-treated
cells were also diminished by the application of NAC or CAT. In addition, BITC
induced apoptosis and autophagy were both enhanced by the pretreatment of
catalase inhibitor, 3-Amino-1,2,4-triazole (3-AT). Pretreatment with specific
inhibitors of autophagy (3-methyladenine or bafilomycin A1) or apoptosis (Z-VAD
FMK) reduced BITC-induced autophagy and apoptosis, respectively, but did not
abolish BITC-induced ROS generation. In conclusion, the present study provides
evidences that BITC caused prostate cancer cell death was dependent on the ROS
status, and clarified the mechanism underlying BITC-induced cell death, which
involves the induction of ROS production, autophagy and apoptosis, and the
relationship between these three important processes.
PMID- 28423629
TI - Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene
and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han
population.
AB - AIMS: To investigate the association of telomerase reverse transcriptase (TERT)
gene polymorphisms and additional gene-gene and gene- environment interaction
with gastric cancer (GC) risk. RESULTS: GC risk was significantly higher in
carriers of G allele of rs2736100 than those with TT genotype (TG+ GG versus TT),
adjusted OR (95%CI) =1.68 (1.26-2.17), and higher in carriers of G allele of
rs2853669 than those with AA genotype (AG+ GG versus AA), adjusted OR (95%CI) =
1.72 (1.19-2.33). We also found that interaction between rs2736100 and smoking
was associated with higher GC risk. Smokers with TG or GG of rs2736100 genotype
have elevated GC risk, compared to never- smokers with TT of rs2736100 genotype,
OR (95%CI) = 3.12 (1.82 -4.61). Pairwise linkage equilibrium (LD) analysis
between SNPs was measured and the D' value between rs2736100 and rs2736109 was
more than 0.8. A haplotype containing the rs2736100- G and rs2736109- A alleles
was associated with a statistically increased GC risk (OR= 2.66, 95%CI= 1.28 -
4.12, p<0.0001). MATERIALS AND METHODS: A total of 1088 participants (686 males,
402 females) were selected, including 360 GC patients and 728 normal
participants. Logistic regression was performed to investigate association
between single nucleotide polymorphisms (SNPs) within TERT gene and GC
susceptibility. Generalized multifactor dimensionality reduction (GMDR) model was
used to screen gene- gene and gene- environment interaction combinations.
CONCLUSIONS: We found that G allele of rs2736100 and G allele of rs2853669 in
TERT gene, interaction between rs2736100 and smoking, and haplotype containing
the rs2736100- G and rs2736109- A alleles were all associated with increased GC
risk.
PMID- 28423631
TI - Why isn't the angiotensin type 1 receptor a target in cancer?
PMID- 28423630
TI - Insufficient hypothalamic angiotensin-converting enzyme 2 is associated with
hypertension in SHR rats.
AB - Angiotensin-Converting Enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin
system (RAS), which is implicated in the pathogenesis of hypertension and other
cardiovascular diseases. In this study we investigated the expression of ACE2 in
the hypothalamus and pituitary tissues and its relationship to hypertension by
comparing them in male WKY and SHR rats. We observed that the plasma levels of
corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and
aldosterone (ALD) were all lower in SHR than WKY rats (P<0.05), whereas plasma
angiotensin II (AngII) levels were higher in SHR rats (P<0.05). Levels of ACE
mRNA and protein were higher in the hypothalamus of SHR than WKY rats (P<0.05).
By contrast, hypothalamic expression of ACE2 protein was lower in SHR rats
(P<0.05), despite comparable mRNA levels in SHR and WKY rats. There were no
differences in the expression levels of ACE, ACE2, AT1 or Mas mRNA in the
pituitaries of SHR and WKY rats (P>0.05). These results suggest that
insufficiency of hypothalamic ACE2 is associated with hypertension in SHR rats.
PMID- 28423632
TI - The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and
CE(A)F chemotherapy response to breast cancer and clinical outcomes.
AB - The PI3K/PTEN/AKT pathway play a critical role in balancing cell growth and
death. Epidemiologic studies suggested that mutations of the PI3K/PTEN/AKT
pathway genes are associated with cancer risk, yet no data are available for PTEN
rs701848, PIK3CA rs2699887, and AKT1 rs2494752 polymorphism and breast cancer(BC)
risk. A case-control study was performed in 920 BC patients and 908 healthy
controls using the TaqMan assay method. Overall, individuals with PTEN rs701848
TC, CC and TC/CC genotypes showed significant increased BC risk (P=0.043,
P=0.002, P=0.008, respectively), and the C allele carriers had a 1.224-fold
significantly increased risk of developing BC (P= 0.003). Moreover, a higher
frequency of AKT rs2494752 AG genotype was observed among cases (P=0.045).
Individuals harboring rs2494752 AG/AA genotype had a vital increased
susceptibility to BC in the dominant model (P=0.039). More importantly, AKT1
rs2494752 GG genotype showed significantly rates of response to NCT chemotherapy
(P=0.048). Furthermore, AKT1 rs2494752 AG genotype carriers showed significantly
shorter DFS time, and GG genotype as the independent prognostic factor (DFS:
adjusted HR=1.523, 95% CI=1.012-2.293, P=0.044; OS: adjusted HR=2.321, 95%
CI=1.281-4.204, P=0.005). Moreover, MDR analysis consistently revealed that the
combination of 3 selected SNPs and 7 known risk factors represented the best
model to predicting BC prognosis. The luciferase assay showed that the G allele
of rs2494752 significantly increased AKT1 promoter activity. These results
suggest that PTEN rs701848 and AKT1 rs2494752 polymorphisms might be a candidate
pharmacogenomic factor to assess the susceptibility of BC and response and
prognosis prediction for interindividualized CE(A)F chemotherapy in BC patients.
PMID- 28423633
TI - Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer.
AB - Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior,
and prognostic biomarkers are needed to stratify patients for appropriate
management. We sought to determine whether long intergenic non-coding RNAs
(lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were
identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data
on 466 ccRCC cases (randomized into discovery and validation sets) annotated for
~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival
predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and
validated in an independent University of Tokyo cohort (P=0.004). In
multivariable analysis, SLINKY expression predicted overall survival independent
of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P < 0.001; Tokyo HR=8.4 (CI,
1.8-40.2), P = 0.007], and by decision tree, ROC and decision curve analysis,
added independent prognostic value. In ccRCC cell lines, SLINKY knockdown reduced
cancer cell proliferation (with cell-cycle G1 arrest) and induced transcriptome
changes enriched for cell proliferation and survival processes. Notably, the
genes affected by SLINKY knockdown in cell lines were themselves prognostic and
correlated with SLINKY expression in the ccRCC patient samples. From a screen for
binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear
Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown
phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it
functions possibly together with HNRNPK in cancer cell proliferation.
PMID- 28423634
TI - Early assessment of tumor response to photodynamic therapy using combined diffuse
optical and diffuse correlation spectroscopy to predict treatment outcome.
AB - Photodynamic therapy (PDT) of cancer involves the use of a photosensitizer that
can be light-activated to eradicate tumors via direct cytotoxicity, damage to
tumor vasculature and stimulating the body's immune system. Treatment outcome may
vary between individuals even under the same regime; therefore a non-invasive
tumor response monitoring system will be useful for personalization of the
treatment protocol. We present the combined use of diffuse optical spectroscopy
(DOS) and diffuse correlation spectroscopy (DCS) to provide early assessment of
tumor response. The relative tissue oxygen saturation (rStO2) and relative blood
flow (rBF) in tumors were measured using DOS and DCS respectively before and
after PDT with reference to baseline values in a mouse model. In complete
responders, PDT-induced decreases in both rStO2 and rBF levels were observed at 3
h post-PDT and the rBF remained low until 48 h post-PDT. Recovery of these
parameters to baseline values was observed around 2 weeks after PDT. In partial
responders, the rStO2 and rBF levels also decreased at 3 h post PDT, however the
rBF values returned toward baseline values earlier at 24 h post-PDT. In contrast,
the rStO2 and rBF readings in control tumors showed fluctuations above the
baseline values within the first 48 h. Therefore tumor response can be predicted
at 3 to 48 h post-PDT. Recovery or sustained decreases in the rBF at 48 h post
PDT corresponded to long-term tumor control. Diffuse optical measurements can
thus facilitate early assessment of tumor response. This approach can enable
physicians to personalize PDT treatment regimens for best outcomes.
PMID- 28423636
TI - Traumatic brain injury and hyperglycemia.
PMID- 28423635
TI - Quantification of HER2 and estrogen receptor heterogeneity in breast cancer by
single-molecule RNA fluorescence in situ hybridization.
AB - Intra-tumor heterogeneity is a pervasive property of human cancers that poses a
major clinical challenge. Here, we describe the characterization, at the
transcriptional level, of the intra-tumor topography of two prominent breast
cancer biomarkers and drug targets, epidermal growth factor receptor 2 (HER2) and
estrogen receptor 1 (ER) in 49 archival breast cancer samples. We developed a
protocol for single-molecule RNA FISH in formalin-fixed, paraffin-embedded tissue
sections (FFPE-smFISH), which enabled us to simultaneously detect and perform
absolute quantification of HER2 and ER mature transcripts in single cells and
multiple tumor regions. We benchmarked our method with standard diagnostic
techniques, demonstrating that FFPE-smFISH is able to correctly classify breast
cancers into well-established molecular subgroups. By counting transcripts in
thousands of single cells, we identified different expression modes and levels of
inter-cellular variability. In samples expressing both HER2 and ER, many cells co
expressed both genes, although expression levels were typically uncorrelated.
Finally, we applied diversity metrics from the field of ecology to assess the
intra-tumor topography of HER2 and ER gene expression, revealing that the spatial
distribution of these key biomarkers can vary substantially even among breast
cancers of the same subtype. Our results demonstrate that FFPE-smFISH is a
reliable diagnostic assay and a powerful method for quantification of intra-tumor
transcriptional heterogeneity of selected biomarkers in clinical samples.
PMID- 28423637
TI - Apigenin inhibits renal cell carcinoma cell proliferation.
AB - Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor
activity in several cancer types. The present study evaluated the effects and
mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found
that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose
and time-dependent manner. A comet assay suggested that apigenin caused DNA
damage in ACHN cells, especially at higher doses, and induced G2/M phase cell
cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)
mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53
dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell
xenograft mouse model. Apigenin treatment reduced tumor growth and volume in
vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors
derived from apigenin-treated mice. These findings suggest that apigenin exposure
induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis,
which collectively suppress ACHN RCC cell proliferation in vitro and in vivo.
Given its antitumor effects and low in vivo toxicity, apigenin is a highly
promising agent for treatment of RCC.
PMID- 28423638
TI - HER inhibitor promotes BRAF/MEK inhibitor-induced redifferentiation in papillary
thyroid cancer harboring BRAFV600E.
AB - Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with
radioiodine represents a good choice for radioiodine-refractory differentiated
thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound
caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance
mechanism, and combination with HER inhibitor to prevent MAPK rebound may
sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To
evaluate if inhibiting both BRAF/MEK and HER can produce stronger
redifferetiation effect, we tested the effects of BRAF/MEK inhibitor
dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on
the expression and function of iodine- and glucose-handling genes in BRAFV600E
positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement
as control. Herein, we showed that lapatinib prevented MAPK rebound and
sensitized BRAFV600E-positive papillary thyroid cancer cells to BRAF/MEK
inhibitors. Dabrafenib/selumetinib alone increased iodine-uptake and toxicity and
suppressed glucose-metablism in BRAFV600E-positive papillary thyroid cancer
cells. When lapatinib was added, more significant effects on iodine- and glucose
handling gene expression, cell membrane location of sodium/iodine symporter as
well as radioiodine uptake and toxicity were observed. Thus, combined therapy
using HER inhibitor and BRAF/MEK inhibitor presented more significant
redifferentiation effect on papillary thyroid cancer cells harboring BRAFV600E
than BRAF/MEK inhibitor alone. In vivo and clinical studies assessing such
combined targeted redifferentiation strategy were warranted.
PMID- 28423639
TI - M2 microglia promotes neurogenesis and oligodendrogenesis from neural
stem/progenitor cells via the PPARgamma signaling pathway.
AB - Neural stem/progenitor cells (NSPCs) are an important source of cells for cell
replacement therapy after nerve injury. How to induce NSPCs differentiation
towards neurons and oligodendrocytes is a challenging issue in neuroscience
research. In the present study, we polarized microglia into M1 and M2 phenotype,
used their supernatants to induce NSPCs differentiation, and investigated the
effects of different microglia phenotypes on NSPCs differentiation and their
mechanisms. We discovered that, after exposure to M1 phenotype supernatant, NSPCs
differentiated into fewer Tuj-1+ and Olig2+ cells, but more GFAP+ cells.
Meanwhile, a significantly increased number of Tuj-1+ and Olig2+ cells and
smaller number of GFAP+ cells were generated by M2 microglia supernatant-induced
NSPCs differentiation. We also observed that 15d-PGJ2, an endogenous ligand of
PPARgamma, was elevated in M2 phenotype supernatant and could activate PPARgamma
expression in NSPCs, whereas use of the PPARgamma inhibitor GW9662, could reduce
the percentage of differentiated neurons and oligodendrocytes. Our study results
confirm that M2 microglia supernatant can activate the PPARgamma signaling
pathway and promote neurogenesis and oligodendrogenesis from NSPCs
differentiation. The present study provides a further theoretical basis for
induction of NSPCs oriented differentiation.
PMID- 28423641
TI - The autophagy process.
PMID- 28423640
TI - The rostromedial tegmental nucleus and alcohol addiction.
PMID- 28423642
TI - Correction: Estrogen-dependent downregulation of hypoxia-inducible factor (HIF)
2alpha in invasive breast cancer cells.
PMID- 28423643
TI - POLE and POLD1 screening in 155 patients with multiple polyps and early-onset
colorectal cancer.
AB - Germline mutations in POLE and POLD1 have been shown to cause predisposition to
colorectal multiple polyposis and a wide range of neoplasms, early-onset
colorectal cancer being the most prevalent. In order to find additional mutations
affecting the proofreading activity of these polymerases, we sequenced its
exonuclease domain in 155 patients with multiple polyps or an early-onset
colorectal cancer phenotype without alterations in the known hereditary
colorectal cancer genes. Interestingly, none of the previously reported mutations
in POLE and POLD1 were found. On the other hand, among the genetic variants
detected, only two of them stood out as putative pathogenic in the POLE gene,
c.1359 + 46del71 and c.1420G > A (p.Val474Ile). The first variant, detected in
two families, was not proven to alter correct RNA splicing. Contrarily, c.1420G >
A (p.Val474Ile) was detected in one early-onset colorectal cancer patient and
located right next to the exonuclease domain. The pathogenicity of this change
was suggested by its rarity and bioinformatics predictions, and it was further
indicated by functional assays in Schizosaccharomyces pombe. This is the first
study to functionally analyze a POLE genetic variant outside the exonuclease
domain and widens the spectrum of genetic changes in this DNA polymerase that
could lead to colorectal cancer predisposition.
PMID- 28423644
TI - Disulfide bond disrupting agents activate the unfolded protein response in EGFR-
and HER2-positive breast tumor cells.
AB - Many breast cancer deaths result from tumors acquiring resistance to available
therapies. Thus, new therapeutic agents are needed for targeting drug-resistant
breast cancers. Drug-refractory breast cancers include HER2+ tumors that have
acquired resistance to HER2-targeted antibodies and kinase inhibitors, and
"Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets
Estrogen Receptor, Progesterone Receptor, and HER2. A significant fraction of
TNBCs overexpress the HER2 family member Epidermal Growth Factor Receptor (EGFR).
Thus agents that selectively kill EGFR+ and HER2+ tumors would provide new
options for breast cancer therapy. We previously identified a class of compounds
we termed Disulfide bond Disrupting Agents (DDAs) that selectively kill EGFR+ and
HER2+ breast cancer cells in vitro and blocked the growth of HER2+ breast tumors
in an animal model. DDA-dependent cytotoxicity was found to correlate with
downregulation of HER1-3 and Akt dephosphorylation. Here we demonstrate that DDAs
activate the Unfolded Protein Response (UPR) and that this plays a role in their
ability to kill EGFR+ and HER2+ cancer cells. The use of breast cancer cell lines
ectopically expressing EGFR or HER2 and pharmacological probes of UPR revealed
all three DDA responses: HER1-3 downregulation, Akt dephosphorylation, and UPR
activation, contribute to DDA-mediated cytotoxicity. Significantly, EGFR
overexpression potentiates each of these responses. Combination studies with DDAs
suggest that they may be complementary with EGFR/HER2-specific receptor tyrosine
kinase inhibitors and mTORC1 inhibitors to overcome drug resistance.
PMID- 28423645
TI - Low forced vital capacity predicts poor prognosis in gastric cancer patients.
AB - Preoperative pulmonary function assessment is used to select surgical candidates
and predict the occurrence of postoperative complications. The present study
enrolled 1210 gastric cancer patients (949 males and 261 females). Forced vital
capacity (FVC) and maximal voluntary ventilation (MVV) were measured as a percent
of predicted values. We then analyzed associations between patient pulmonary
function and both prognosis and postoperative complications. Patient 1-, 3- and 5
year overall survival rates were 88.8%, 65.7% and 53.0%, respectively. FVC and
MVV optimal cutoff values were 87.0 (P=0.003) and 83.6 (P=0.026), respectively.
Low FVC and low MVV were associated with higher rates of postoperative fever
(23.8% vs. 13.9%, P<0.001; 17.8% vs. 13.3%, P=0.049, respectively) and poor
patient prognosis (5-year overall survival: 43.5% vs. 57.6%, P=0.003; 51.8% vs.
54.3%, P=0.026, respectively). Only low FVC was an independent prognostic
predictor for gastric cancer (P=0.012). In subgroup analyses, FVC was not
associated with stage I or II gastric cancer patient prognoses (P>0.05), but low
FVC was an independent risk factor for poor prognosis in stage III gastric cancer
cases (P=0.004). These findings indicate that low FVC is predictive of poorer
prognosis and higher risk of postoperative fever in gastric cancer patients.
PMID- 28423646
TI - TIM-3 is a potential prognostic marker for patients with solid tumors: A
systematic review and meta-analysis.
AB - Accumulated studies have demonstrated the important role of T cell immunoglobulin
and mucin-domain-containing molecule-3 (TIM-3) in various solid tumors and
indicated its correlation with patients' survival. To further verify the
prognostic significance of TIM-3 in cancer patients and its correlation with
tumor, we performed this meta-analysis including seven studies searched from
PubMed, Web of Science, and Embase till July 2016. A total of 869 patients were
used to analyze the association between TIM-3 expression and patients' overall
survival (OS). The pooled results showed that higher expression of TIM-3 was
significantly correlated to shorter OS (7 studies, HR=1.89; 95% CI: 1.38-2.57; P<
0.001). In addition, higher TIM-3 expression was associated with advanced tumor
stage (3 studies, III/IV vs. I/II, RR=2.02; 95% CI: 1.45-2.81; P< 0.001). In
conclusion, our study highlights the role of TIM-3 as a potential prognostic
marker and a promising therapeutic target in solid tumors.
PMID- 28423647
TI - Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and
progression of epithelial ovarian carcinoma by regulating activity of ATG3.
AB - Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to
be associated with the pathogenesis of multiple malignancies. However, little is
known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this
study, we found that the expression of Meg3 was lower in epithelial ovarian
carcinoma, and has potential to be considered as a biomarker for ovarian cancer.
After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3,
phenotypic changes and autophagy-related molecules were examined. Upregulation of
Meg3 inhibited cell proliferation, plate colony formation, induced cell cycle
arrest in G2 phases, and promoted apoptosis. Observation of autophagosomes was
performed by transmission electron microscopy. The expression levels of LC3-II,
ATG3, LAMP1 were elevated, while SQSTM1/p62 expression declined. Upregulated
expression of Meg3 also suppressed tumorigenesis in vivo in a xenograft mouse
model through upregulating ATG3 expression. RIP (ribonucleoprotein
immunoprecipitation) and RNA pull-down assays showed that Meg3 was co
immunoprecipitated with ATG3. In addition, Meg3 protected ATG3 mRNA from
degradation following treatment with actinomycin D. Overall, our results suggest
that the lncRNA Meg3 acts as a tumor suppressor in EOC by regulating ATG3
activity and inducing autophagy.
PMID- 28423648
TI - Polyisoprenylated cysteinyl amide inhibitors disrupt actin cytoskeleton
organization, induce cell rounding and block migration of non-small cell lung
cancer.
AB - The malignant potential of Non-Small Cell Lung Cancer (NSCLC) is dependent on
cellular processes that promote metastasis. F-actin organization is central to
cell migration, invasion, adhesion and angiogenesis, processes involved in
metastasis. F-actin remodeling is enhanced by the overexpression and/or hyper
activation of some members of the Rho family of small GTPases. Therefore, agents
that mitigate hyperactive Rho proteins may be relevant for controlling
metastasis. We previously reported the role of polyisoprenylated cysteinyl amide
inhibitors (PCAIs) as potential inhibitors of cancers with hyperactive small
GTPases. In this report, we investigate the potential role of PCAIs against NSCLC
cells and show that as low as 0.5 MUM PCAIs significantly inhibit 2D and 3D NCI
H1299 cell migration by 48% and 45%, respectively. PCAIs at 1 MUM inhibited 2D
and 3D NCI-H1299 cell invasion through Matrigel by 50% and 85%, respectively.
Additionally, exposure to 5 MUM of the PCAIs for 24 h caused at least a 66% drop
in the levels of Rac1, Cdc42, and RhoA and a 38% drop in F-actin intensity at the
cell membrane. This drop in F-actin was accompanied by a 73% reduction in the
number of filopodia per cell. Interestingly, the polyisoprenyl group of the PCAIs
is essential for these effects, as NSL-100, a non-farnesylated analog, does not
elicit similar effects on F-actin assembly and organization. Our findings
indicate that PCAIs disrupt F-actin assembly and organization to suppress cell
motility and invasion. The PCAIs may be an effective therapy option for NSCLC
metastasis and invasion control.
PMID- 28423649
TI - Stellettin B induces apoptosis in human chronic myeloid leukemia cells via
targeting PI3K and Stat5.
AB - Novel agents are still urgently expected for therapy of chronic myeloid leukemia
(CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a
triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562
and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell
proliferation with IC50 as 0.035 MUM and 0.95 MUM respectively. While no obvious
cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B
treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with
increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9. In
addition, dose-dependent increase of reactive oxygen species (ROS) and loss of
mitochondrial membrane potential (MMP) occurred. Meanwhile, Stel B inhibited
phosphorylation of Stat5, expression of 4 PI3K catalytic isoforms, and
phosphorylation of the downstream effectors including PDK1 and Akt, suggesting
that inhibition against Stat5 and PI3K might be involved in the apoptosis
inducing effect. Combination of Stel B with Imatinib with ratio as IC50 Stel B :
5*IC50 Imatinib led to synergistic effect. Stel B might become a promising
candidate for CML therapy alone or together with Imatinib.
PMID- 28423650
TI - MiR-425-5p promotes invasion and metastasis of hepatocellular carcinoma cells
through SCAI-mediated dysregulation of multiple signaling pathways.
AB - MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC)
progression and are key determinants of prognosis. In this study, we found that
miR-425-5p was elevated in HCC and correlated with poor prognostic
clinicopathological features and low post-operative long-term survival.
Multivariate survival analysis indicated that miR-425-5p expression was an
independent risk factor for overall and disease-free survival. Interestingly, miR
425-5p promoted invasion and metastasis by HCC cells, but not HCC cell
proliferation or apoptosis in vitro. SCAI and PTEN were determined to be
downstream targets of miR-425-5p. miR-425-5p-mediated effects were inhibited by
ectopic expression of SCAI, and PTEN exhibited a smaller inhibitory effect. SCAI
also suppressed PTEN expression. In addition, miR-425-5p promoted epithelial-to
mesenchymal transition (EMT), which was antagonized by SCAI. miR-425-5p also
promoted HCC cell invasion and metastasis via SCAI-mediated dysregulation of
integrin beta1-Fak/Src-RhoA/CDC42, PTEN-AKT, and TIMP2-MMP2/MMP9 signaling.
Finally, miR-425-5p promoted metastasis in a xenograft mouse model of HCC. These
results indicate that miR-425-5p facilitates EMT and extracellular matrix
degradation and promotes HCC metastasis through SCAI-mediated dysregulation of
multiple signaling pathways. MiR-425-5p is therefore a potential prognostic
biomarker and novel therapeutic target in HCC.
PMID- 28423651
TI - Succinate dehydrogenase B-deficient cancer cells are highly sensitive to
bromodomain and extra-terminal inhibitors.
AB - Mutations in succinate dehydrogenase B (SDHB) gene are frequently observed in
several tumors and associated with poor prognosis in these tumors. Therefore,
drugs effective for SDHB-deficient tumors could fulfill an unmet medical need. In
addition, such drugs would have an advantage in that selection of patients with
SDHB-mutant cancer could increase the probability of success in clinical trials.
Currently, however, the characteristics of SDHB-deficient cancers are not
completely understood. Here, we established SDHB knockout cancer cell lines from
human colon cancer HCT116 cells using the clustered regularly interspaced short
palindromic repeat (CRISPR)/Cas9 knockout system, and clarified its metabolic
characteristics.In the SDHB knockout cells, succinate was accumulated and
fumarate was decreased. The oxygen consumption rate was decreased while the
extracellular acidification rate was increased in the SDHB knockout cells.
Accordingly, an enhanced glycolysis pathway in the SDHB knockout cells was
demonstrated by metabolomics analysis. Tracer experiments showed bidirectional
metabolic flow in the tricarboxylic acid (TCA) cycle, possibly to maintain the
necessary amounts of metabolites in the SDHB knockout cells. The proliferation of
SDHB knockout cells was suppressed by a glycolysis inhibitor but not by a
mitochondrial inhibitor. Additionally, partial dependence on glutaminolysis was
observed in the SDHB knockout cells. Compound screening revealed that a
bromodomain and extra-terminal (BET) inhibitor, which downregulated c-Myc,
suppressed the growth of the SDHB knockout cells more potently than that of
control cells. These findings provide an understanding of the metabolic
characteristics of SDHB-deficient cancer and its vulnerabilities, which may lead
to new therapeutic options.
PMID- 28423652
TI - Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer
through SPIN1 regulation.
AB - MiR-29 family dysregulation occurs in various cancers including breast cancers.
We investigated miR-29b-1 functional role in human triple negative breast cancer
(TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was
downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1
5p correlated with TNBC regenerative potential, we evaluated cancer stem cell
enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20
produced primary, secondary and tertiary mammospheres, which were progressively
enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression
inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic
overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness
and paclitaxel resistance repressing WNT/betacatenin and AKT signaling pathways
and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b
1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell
lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed
that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1
mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue
by SPIN1miScript protector, determined the reversal of the molecular effects
produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation
impacts on multiple oncogenic features of TNBC cells and their renewal potential,
acting, at least partly, through SPIN1, and suggest that both these factors
should be evaluated as new possible therapeutic targets against TNBC.
PMID- 28423653
TI - A novel microRNA signature predicts survival in stomach adenocarcinoma.
AB - Recent microRNA (miRNA) expression profiling studies suggest the clinical use of
miRNAs as potential prognostic biomarkers in various malignancies. In this study,
aiming to identify microRNAs with prognostic value for overall survival (OS) in
stomach adenocarcinoma (STAD) patients, we analyzed the miRNA expression profiles
and the associated clinical characteristics in 380 STAD samples from The Cancer
Genome Atlas (TCGA) dataset. An eight-miRNA signature for predicting OS in STAD
patients was identified and self-validated by survival analysis and semi
supervised principal components method. We developed a linear prognostic model
composed of these miRNAs to divide patients into high- and low-risk groups
according to the calculated prognostic scores. Kaplan-Meier analysis demonstrated
that patients in the high-risk group had worse OS compared with patients in the
low-risk group. Notably, this miRNA prognostic model showed prognostic
significance to the STAD patients in early stages and the chemo-resistant
patients, who would potentially benefit from additional medical interventions.
Finally, this eight-miRNA signature is an independent prognostic biomarker and
demonstrates a good predictive performance for 5-year survival. Thus, this
signature may serve as a novel biomarker for predicting survival as well as
chemotherapy response in STAD patients.
PMID- 28423654
TI - Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced
senescence.
AB - Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers
and is believed to enhance tumorigenic potential and chemotherapy resistance
through the inhibition of apoptosis and senescence. We previously reported that
Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its
ability to prevent reactive oxygen species (ROS) generation. In this report, we
demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically
mitochondrial ROS, and that these events are upstream of activation of the DNA
damage response, another necessary step toward senescence. Mcl-1's anti
senescence activity also involves the unique ability to inhibit ROS formation by
preventing the upregulation of pro-oxidants. Specifically, we found that NADPH
oxidases (NOXs) are regulated by Mcl-1 and that NOX4 expression in particular is
a required step for CIS induction that is blocked by Mcl-1. Lastly, we illustrate
that by preventing expression of NOX4, Mcl-1 limits its availability in the
mitochondria, thereby lowering the production of mitochondrial ROS during CIS.
Our studies not only define the essential role of Mcl-1 in chemoresistance, but
also for the first time link a key pro-survival Bcl-2 family member with the NOX
protein family, both of which have significant ramifications in cancer
progression.
PMID- 28423655
TI - Sequence-based predictive modeling to identify cancerlectins.
AB - Lectins are a diverse type of glycoproteins or carbohydrate-binding proteins that
have a wide distribution to various species. They can specially identify and
exclusively bind to a certain kind of saccharide groups. Cancerlectins are a
group of lectins that are closely related to cancer and play a major role in the
initiation, survival, growth, metastasis and spread of tumor. Several
computational methods have emerged to discriminate cancerlectins from non
cancerlectins, which promote the study on pathogenic mechanisms and clinical
treatment of cancer. However, the predictive accuracies of most of these
techniques are very limited. In this work, by constructing a benchmark dataset
based on the CancerLectinDB database, a new amino acid sequence-based strategy
for feature description was developed, and then the binomial distribution was
applied to screen the optimal feature set. Ultimately, an SVM-based predictor was
performed to distinguish cancerlectins from non-cancerlectins, and achieved an
accuracy of 77.48% with AUC of 85.52% in jackknife cross-validation. The results
revealed that our prediction model could perform better comparing with published
predictive tools.
PMID- 28423657
TI - Identification and characterization of RASSF1C piRNA target genes in lung cancer
cells.
AB - RASSF1C up-regulates important genes involved in lung cancer cell growth,
including a stem cell self-renewal gene, piwil1. In this article, we report the
identification of small noncoding PIWI-interacting RNAs (piRNAs) in lung cancer
cells over-expressing RASSF1C. A piRNA microarray screen was performed using RNA
isolated from the lung cancer cell line H1299 stably over-expressing RASSF1C and
corresponding control. The piRNA microarray screen identified several piRNAs that
are regulated by RASSF1C and we have validated the expression of two up-regulated
piRNAs (piR-34871 and piR-52200) and two down-regulated piRNAs (piR-35127 and piR
46545) in lung cancer cells with silenced and over-expressed RASSF1C using RT
PCR. We also assessed the expression of these four piRNAs in lung tumor and
matched normal tissues (n = 12). We found that piR-34871 and piR-52200 were up
regulated in 58% and 50%, respectively; while piR-35127 and piR-46545 were down
regulated in 50% in lung tumor tissues tested. The expression of piR-35127 was
inversely correlated with RASSF1C expression in 10/12 tumor tissues. Over
expression of piR-35127 and piR-46545 and knock-down of piR-34871 and piR-52200
significantly reduced normal lung and breast epithelial cell proliferation and
cell colony formation as well as proliferation of lung cancer cell lines (A549
and H1299) and breast cancer cell lines (Hs578T and MDA-MB-231). This suggests
that these novel piRNAs may potentially be involved in regulating lung cell
transformation and tumorigenesis. RASSF1C may potentially modulate the expression
of its piRNA target genes through attenuation of the AMPK pathway, as over
expression of RASSF1C resulted in reduction of p-AMPK, p21, and p27 protein
levels.
PMID- 28423656
TI - Effect of Y6, an epigallocatechin gallate derivative, on reversing doxorubicin
drug resistance in human hepatocellular carcinoma cells.
AB - Cancer cells can acquire resistance to a wide variety of diverse and unrelated
drugs, this phenomenon is termed multidrug resistance (MDR). Multidrug resistance
has been an obstacle to the success of cancer chemotherapy. The present study
investigated the reversal effect of Y6, a new compound obtained by chemically
modifying the structure of epigallocatechin-3-gallate (EGCG) extracted from green
tea. Y6 was proven to be effective in inhibiting cell proliferation and reversing
drug resistance in doxorubicin (DOX) resistant human hepatocellular carcinoma
cells (BEL-7404/DOX). BEL-7404/DOX cells were treated with either doxorubicin
combination regimen (doxorubicin plus Y6 or epigallocatechin-3-gallate or
verapamil separately) or doxorubicin alone. The results showed that cell
proliferation was inhibited and late cell apoptosis increased in the combination
treatment group, especially in the group treated with doxorubicin plus Y6.
Further analysis revealed that the expressions of hypoxia-inducible factor-1alpha
and multidrug resistance 1/P-glycoprotein decreased at both messenger RNA and
protein levels by treatments with combined drugs compared to doxorubicin alone.
Our results indicated that Y6, as a drug resistance reversal agent, increased the
sensitivity of drug resistant cells to doxorubicin. The mechanisms of actions of
Y6 in reversal effect were associated with the decreased expression of hypoxia
inducible factor-1alpha and multidrug resistance 1/P-glycoprotein.
PMID- 28423658
TI - Correlation between polymorphisms in microRNA-regulated genes and cervical cancer
susceptibility in a Xinjiang Uygur population.
AB - We explored the correlation between single nucleotide polymorphisms (SNPs) and
susceptibility to cervical cancer (CC) in a Xinjiang Uygur population. Ten SNPs
in eight miRNA-regulated genes were selected for analysis. Odds ratios (ORs) and
95% confidence intervals (95% CIs) were calculated using unconditional logistic
regression analysis. Multivariate logistic regression analysis was used to detect
correlations between SNPs and CC. We found that minor allele "C" of rs512715 in
NEAT1 was associated with an increased risk of CC in the allele, codominant,
dominant, overdominant and log-additive models. Minor allele "C" of rs4777498 in
CELF6 was associated with an increased risk of CC in the recessive model. Minor
allele "C" of rs3094 in RNASE4 was associated with increased risk of CC in the
allele, dominant and log-additive models. In clinical stage III/IV CC patients,
minor allele "C" of rs3094 in RNASE4 and minor allele "C" of rs8004334 in JDP2
were associated with increased risk. In subtype squamous carcinoma CC patients,
minor allele "C" of rs512715 in NEAT1 and minor allele "C" of rs3094 in RNASE4
were associated with increased risk. In subtype adenocarcinoma CC patients, minor
allele "C" of rs3094 in RNASE was associated with increased risk.
PMID- 28423659
TI - Targeting HOX/PBX dimers in cancer.
AB - The HOX and PBX gene families encode transcription factors that have key roles in
establishing the identity of cells and tissues in early development. Over the
last 20 years it has become apparent that they are also dysregulated in a wide
range of solid and haematological malignancies and have a predominantly pro
oncogenic function. A key mode of transcriptional regulation by HOX and PBX
proteins is through their interaction as a heterodimer or larger complex that
enhances their binding affinity and specificity for DNA, and there is growing
evidence that this interaction is a potential therapeutic target in malignancies
that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma,
and acute myeloid leukaemia. This review summarizes the roles of HOX and PBX
genes in cancer and assesses the therapeutic potential of HOX/PBX dimer
inhibition, including the availability of biomarkers for its application in
precision medicine.
PMID- 28423660
TI - Progerin impairs vascular smooth muscle cell growth via the DNA damage response
pathway.
AB - Mutations of the lamin A gene cause various premature aging syndromes, including
Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner syndrome. In HGPS
(but not atypical Werner syndrome), extensive loss of vascular smooth muscle
cells leads to myocardial infarction with premature death. The underlying
mechanisms how single gene mutations can cause various phenotypes are largely
unknown. We performed an interactome analysis using mutant forms of lamin A
involved in progeroid syndromes. We found that the mutant lamin A responsible for
HGPS, known as progerin, could not bind to proteins related to the DNA damage
response, including DNA-dependent protein kinase (DNA-PK). In contrast, wild-type
lamin A and lamin A mutants causing atypical Werner syndrome were able to bind to
these molecules. We also found that forced expression of progerin in vascular
smooth muscle cells led to activation of DNA-PK and cellular growth arrest, while
knockdown of DNA-PK attenuated this. Deletion of p53 also improved the inhibition
of cell growth due to forced expression of progerin. These findings suggested
that progerin activates the DNA damage response pathway and that dysregulation of
this pathway may be responsible for the development of cardiovascular pathology
in patients with HGPS.
PMID- 28423661
TI - Examining the association between anthropometric parameters and telomere length
and mortality risk.
AB - A shorter telomere length is associated with several systemic disorders. Telomere
length may be an informative biomarker for the maintenance of the overall health
status and mortality. There are a limited number of empirical studies concerning
the effect of anthropometric parameters on telomere length. The data are derived
from the National Health and Nutrition Examination Survey from 1999 to 2002. The
primary outcomes of this study were to examine the potential relationships
between the anthropometric indices and the telomere length, while secondary
outcomes of this study was to investigate the association between different
anthropometric indices and mortality risk. A significant positive correlation was
noted between the mean telomere length and the thigh circumference (TC) and calf
circumference (CC) in all designed models. Participants in the highest TC and CC
quartiles tended to have a longer telomere length and lowered the hazards for all
cause mortality to 43% and 57%, respectively. Notably, the anthropometric indices
involving the CC with higher values seemed to be surrogate markers for the
reduction of the risk of all-cause, cardiovascular and malignancy-related
mortality (all P < 0.05). The CCmay be a valuable tool to guide public health
policy and a clinical prognostic indicator for the risk of mortality.
PMID- 28423662
TI - Comparative analysis of HPV16 gene expression profiles in cervical and in
oropharyngeal squamous cell carcinoma.
AB - Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of
a fraction of oropharyngeal carcinoma. Few studies compared the viral expression
profiles in the two types of tumor. We analyzed HPV genotypes and viral load as
well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene
expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study
included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC,
along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic
tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found
higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell)
compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well
as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in
oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical
SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression
pattern showed statistically significant higher levels of E6*I versus E6*II
isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I
versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II
and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal
SCC suggesting different carcinogenic mechanisms in the two types of HPV-related
cancers.
PMID- 28423665
TI - IL-33-induced alternatively activated macrophage attenuates the development of
TNBS-induced colitis.
AB - Accumulated data have shown that alternatively activated macrophage exerts a
modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a
critical modulator in adaptive and innate immune, has been implicated in
autoimmunity and inflammation. Previously, we have reported that IL-33 functions
as a protective modulator in TNBS-induced colitis, which is closely related to a
Th1-to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33
primes macrophage into alternatively activated macrophages (AAM) in TNBS-induced
colitis. The strong polarized effect of IL-33 was tightly associated with the
markedly increased induction of Th2-type cytokines. To confirm the beneficial
effects of AAM induced by IL-33, peritoneal AAMs isolated from IL-33-treated mice
were transferred to recipient mice with TNBS colitis. The adoptive transfer
resulted in prominent inhibition of disease activity and inflammatory cytokines
in the TNBS-treated mice. In conclusion, our data provide clear evidence that IL
33 plays a protective role in TNBS-induced colitis, which is closely related to
AAM polarization.
PMID- 28423666
TI - Negative LC3b immunoreactivity in cancer cells is an independent prognostic
predictor of prostate cancer specific death.
AB - BACKGROUND: Autophagy is a catabolic cellular process used for degradation of
cytoplasmic organelles and preservation of cell viability. In this study we aimed
to analyse the level of autophagy markers in benign and malignant prostate tissue
and to evaluate the prognostic properties for patients with prostate cancer
(PCa). RESULTS: LC3b expression was significantly upregulated in PCa, especially
in metastatic and castration-resistant PCa samples compared to benign prostate
tissue (p<0.001). Evaluation of expression in malignant radical prostatectomy
specimens revealed an inverse association with preoperative serum PSA levels
(p=0.02) and Gleason Score (p=0.07). LC3b immunoreactivity was identified as a
novel predictor of PCa specific death after radical prostatectomy, independent of
Gleason score, tumour stage, and surgical margin status in a multivariable cox
regression analysis (hazard ratio 0.09, 95% confidence interval 0.01-0.69,
p=0.021). A significant association of ATG-5 and Beclin 1 with LC3b expression
could be noticed (p<0.001), but no link with other clincopathologic parameters
was observed. METHODS: A Tissue microarray containing 468 formalin-fixed,
paraffin-embedded prostate tissue cores was stained immunohistochemically for
major autophagy proteins LC3b, ATG5 and Beclin 1. Immunoreactivity was
semiquantitatively scored and correlated with pathologic and clinical parameters,
including tumour stage, Gleason score, preoperative PSA level, biochemical
recurrence rate and survival. The median clinical follow-up was 132 months.
CONCLUSION: LC3b was significantly overexpressed in malignant compared to benign
prostate tissue. However, positive LC3b immunoreactivity in PCa, as a marker of
increased autophagy, was independently associated with a reduced disease-specific
mortality.
PMID- 28423667
TI - Saline is a more appropriate solution for microvesicles for flow cytometric
analyses.
AB - Microvesicles (MVs) are carriers of molecular and oncogenic signatures present in
subsets of tumor cells and tumor-associated stroma, and a focus of cancer
research. Although methods to detect MVs are mature, we were concerned that the
buffer used could lead to false results when quantitating MVs by flow cytometry.
In this work,we detected MVs by flow cytometry withthree different solutions:
water, saline, and phosphate-buffered saline (PBS). The results demonstrated that
PBS, when reacted with annexin V binding buffer, produced nano-sized vesicles
even when there were no MVs in the sample. No similar events occurred in the
saline and water groups (P < 0.01). Annexin V positive rate increased
significantly when PBS was used as the buffer, compared to saline and water.
These false negative results were also observed when we quantified some markers
of MVs such as CD3 and CD19. A probable explanation for these findings is the
production of insoluble Ca(H2PO4)2 or Ca3PO4 from calcium in the binding buffer
and phosphate in PBS. Thus, considering the osmotic pressure of water, we suggest
that saline is a more suitable buffer when counting MVs by flow cytometry.
PMID- 28423668
TI - AHNAK2 is a potential prognostic biomarker in patients with PDAC.
AB - BACKGROUND: AHNAK nucleoprotein 2 (AHNAK2) belongs to the AHNAK protein family.
The studies of AHNAK2 are limited. A recent study reported that AHNAK2 might be a
biomarker for pancreatic ductal adenocarcinoma (PDAC); however, tissue-based
experiments have not been conducted. The aim of this study was to determine the
tissue expression of AHNAK2 and to find the correlation between AHNAK2 and
overall survival rate in PDAC. RESULTS: AHNAK2 is highly expressed in PDAC (n=79)
compared with adjacent normal tissues (n=64, P<0.001). Overexpression of AHNAK2
showed a significant relationship with a lower overall survival rate (P=0.033) in
PDAC patients. The predictive value of increased expression of AHNAK2 remains
relevant in patients with AJCC grade above II (n=43, P=0.006) or lymph node
metastasis (n=32, P=0.004). Cox regression analysis showed that AHNAK2 expression
(P=0.003) and pathology grade (P<0.001) are independent prognostic factors for
PDAC. The nomogram model was performed to predict the 1- and 3-year survival
rates based on Cox regression. The C-index was 0.61. The calibration curves were
also made to show the association between the observed and predicted probability
of the overall survival rates. MATERIALS AND METHODS: AHNAK2 expression was
performed in tissue microarrays by immunohistochemistry. The overall survival
rate analysis was performed using the Kaplan-Meier method, Cox proportional
hazards regression, and a nomogram model. CONCLUSIONS: AHNAK2 is overexpressed in
PDAC tissues and is an independent prognostic factor in patients with PDAC.
PMID- 28423669
TI - The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the
stemness and radiation response of glioma stem cells.
AB - Despite advances in novel therapeutic approaches for the treatment of
glioblastoma (GBM), the median survival of 12-14 months has not changed
significantly. Therefore, there is an imperative need to identify molecular
mechanisms that play a role in patient survival. Here, we analyzed the expression
and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of
E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression
was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM
with poor prognosis, in GBM specimens derived from short-term survivors and in
glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell
proliferation and arrested the cells in the G1?S phase of the cell cycle in
various cancer cell lines. In addition, silencing of TALNEC2 decreased the self
renewal and mesenchymal transformation of GSCs, increased sensitivity of these
cells to radiation and prolonged survival of mice bearing GSC-derived xenografts.
Using miRNA array analysis, we identified specific miRNAs that were altered in
the silenced cells that were associated with cell-cycle progression,
proliferation and mesenchymal transformation. Two of the downregulated miRNAs,
miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and
mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1
regulated lncRNA that is highly expressed in GBM and in tumors from patients of
short-term survival. The expression of TALNEC2 is associated with the increased
tumorigenic potential of GSCs and their resistance to radiation. We conclude that
TALNEC2 is an attractive therapeutic target for the treatment of GBM.
PMID- 28423670
TI - Invasive Fusobacterium nucleatum activates beta-catenin signaling in colorectal
cancer via a TLR4/P-PAK1 cascade.
AB - The underlying mechanism of Fusobacterium nucleatum (Fn) in the carcinogenesis of
colorectal cancer (CRC) is poorly understood. Here, we examined Fn abundance in
CRC tissues, as well as beta-catenin, TLR4 and PAK1 protein abundance in Fn
positive and Fn negative CRCs. Furthermore, we isolated a strain of Fn (F01) from
a CRC tissue and examined whether Fn (F01) infection of colon cancer cells
activated beta-catenin signaling via the TLR4/P-PAK1/P-beta-catenin S675 cascade.
Invasive Fn was abundant in 62.2% of CRC tissues. TLR4, PAK1 and nuclear beta
catenin proteins were more abundant within Fn-positive over Fn-negative CRCs (P <
0.05). Fn and its lipopolysaccharide induced a significant increase in TLR4/P
PAK1/P-beta-catenin S675/C-myc/CyclinD1 protein abundance, as well as in the
nuclear translocation of beta-catenin. Furthermore, inhibition of TLR4 or PAK1
prior to challenge with Fn significantly decreased protein abundance of P-beta
catenin S675, C-myc and Cyclin D1, as well as nuclear beta-catenin accumulation.
Inhibition of TLR4 significantly decreased P-PAK1 protein abundance, and for the
first time, we observed an interaction between TLR4 and P-PAK1 using
immunoprecipitation. Our data suggest that invasive Fn activates beta-catenin
signaling via a TLR4/P-PAK1/P-beta-catenin S675 cascade in CRC. Furthermore, TLR4
and PAK1 could be potential pharmaceutical targets for the treatment of Fn
related CRCs.
PMID- 28423671
TI - Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic
cancer.
AB - Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United
States with a five-year patient survival rate of only 6%. Early detection and
treatment of this disease is hampered due to lack of reliable diagnostic and
prognostic markers. Recent studies have shown that dynamic changes in the global
DNA methylation and gene expression patterns play key roles in the PC
development; hence, provide valuable insights for better understanding the
initiation and progression of PC. In the current study, we used DNA methylation,
gene expression, copy number, mutational and clinical data from pancreatic
patients. We independently investigated the DNA methylation and differential gene
expression profiles between normal and tumor samples and correlated methylation
levels with gene expression patterns. We observed a total of ~23-thousand
differentially methylated CpG sites (Deltabeta>=0.1) between normal and tumor
samples, where majority of the CpG sites are hypermethylated in PC, and this
phenomenon is more prominent in the 5'UTRs and promoter regions compared to the
gene bodies. Differential methylation is observed in genes associated with the
homeobox domain, cell division and differentiation, cytoskeleton, epigenetic
regulation and development, pancreatic development and pancreatic signaling and
pancreatic cancer core signaling pathways. Correlation analysis suggests that
methylation in the promoter region and 5'UTR has mostly negative correlations
with gene expression while gene body and 3'UTR associated methylation has
positive correlations. Regulatory element analysis suggests that HOX cluster and
histone core proteins are upstream regulators of hypomethylation, while SMAD4,
STAT4, STAT5B and zinc finger proteins (ZNF) are upstream regulators of
hypermethylation. Non-negative matrix factorization (NMF) clustering of
differentially methylated sites generated three clusters in PCs suggesting the
existence of distinct molecular subtypes. Cluster 1 and cluster 2 showed samples
enriched with clinical phenotypes like neoplasm histological grade and pathologic
T-stage T3, respectively, while cluster 3 showed the enrichment of samples with
neoplasm histological grade G1. To the best of our knowledge, this is the first
genome-scale methylome analysis of PC data from TCGA. Our clustering analysis
provides a strong basis for future work on the molecular subtyping of epigenetic
regulation in pancreatic cancer.
PMID- 28423672
TI - alpha2,3-sialyltransferase type I regulates migration and peritoneal
dissemination of ovarian cancer cells.
AB - Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic
cancers due to advanced stage presentation, peritoneal dissemination, and
refractory ascites at diagnosis. We investigated the role of alpha2,3
sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and
human EOC tissue arrays. We found that high expression of ST3GalI was associated
with advanced stage EOC. Transwell migration and cell invasion assays showed that
high ST3GalI expression enhanced migration of EOC cells. We also observed that
there was a linear relation between ST3GalI expression and epidermal growth
factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI
expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation
experiments demonstrated that ST3GalI and EGFR were present in the same protein
complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I
(SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse
model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the
anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that
ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via
EGFR signaling. This suggests alpha2,3-linked sialylation inhibitors in
combination with EGFR inhibitors could be effective agents for the treatment of
EOC.
PMID- 28423673
TI - Ceruloplasmin as a prognostic marker in patients with bile duct cancer.
AB - BACKGROUND AND AIMS: Bile duct cancer is one of the lethal cancers, presenting
difficulties in early diagnosis and limited treatment modalities. Despite current
advances in biomarker research, most studies have been performed in Western
populations. Therefore, the purpose of this study was to determine a prognostic
marker for bile duct cancer, especially in Korean patients, whose incidence of
bile duct cancer is high. RESULTS: Comparing cancer and normal bile duct tissue,
we identified 29091 differentially expressed genes. CP, SCEL, and MUC16 had
positive coefficients with a log2 ratio >1 for advanced T, N stage and perineural
invasion cancer tissue. Strong immunohistochemical expression of ceruloplasmin
was dominant in tumors with advanced T stage (p>0.999) and perineural invasion
(p=0.316). PATIENTS AND METHODS: We performed tissue microarray experiment with
79 bile duct cancer tissue samples and 21 normal bile duct tissue samples.
Candidate genes that has positive correlation with T, N stage and perineural
invasion were drawn with multivariate analysis. Tissue expression of the genes
was evaluated with an immunohistochemical study. CONCLUSIONS: Ceruloplasmin is
supposed to be related with advanced T stage and perineural invasion, having a
possibility as a candidate prognostic marker for bile duct cancer.
PMID- 28423674
TI - A single center clinical analysis of children with high-risk neuroblastoma.
AB - : The current multidisciplinary treatment for patients with high-risk
neuroblastoma (NB) is the common census. However, protocols and opinions are
different in different regions and institutions. We aimed to assess the protocol
formulated by Chinese Children's Cancer Group study in 2009, and the impact of
surgery extent was highlightly evaluated. METHODS: This study enrolled patients
with high-risk neuroblastoma between 2009 and 2014 in Department of Pediatric
Oncology of Tianjin Medical University Cancer Institute and Hospital. The
clinical characteristics of patients were illustrated and surgery extent was
evaluated by the impact on survival rate. RESULTS: The 3-year overall survival
(OS) and progression-free survival (PFS) were 56.2% and 50.5%, respectively. LDH
(P<0.001), bone marrow metastasis at time of diagnosis (P=0.001), bone marrow
negative after neoadjuvant chemotherapy (P<0.001), radiotherapy (P<0.001) were
significant predictors of OS and PFS. And surgery extent had no impact on the
enhancement of high-risk neuroblastoma patients in short time. CONCLUSIONS: This
study showed no substantial survival benefit in patients with high-risk NB
undergoing gross total tumor resection. Multidisciplinary intensive treatment was
essential, especially for patients received subtotal tumor resection. Longer term
follow-up is needed to survey complications in surviving patients who received
intensive chemotherapy and radiotherapy.
PMID- 28423675
TI - miR-219-5p targets CaMKIIgamma to attenuate morphine tolerance in rats.
AB - Morphine tolerance is a clinical challenge in pain management. Emerging evidence
suggests that microRNA (miRNA) plays a regulatory role in the development of
morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein
kinase II gamma (CaMKIIgamma) to activate central pain sensitization via N-methyl
D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p
attenuates morphine tolerance by targeting CaMKIIgamma. We found that the
expression of miR-219-5p was decreased significantly after chronic morphine
treatment. Overexpression of miR-219-5p by lentivirus injection prevents the
development of morphine tolerance. CaMKIIgamma, the target gene of miR-219-5p was
downregulated by overexpression of miR-219-5p both in vivo and in vitro.
Furthermore, we found that lentiviral-mediated miR-219-5p decreased the
expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine
tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in
alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway.
Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine
tolerance.
PMID- 28423676
TI - Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial
mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation.
AB - Tumor-associated macrophages (TAMs) are key components of tumor microenvironment
(TME) during tumorigenesis and progression. However, the role of TAMs in lung
adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism
underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT)
of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer
sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it
plays critical role in the invasion and metastasis. Here, we found that in lung
adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and
LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through
the transforming growth factor-beta1(TGF-beta1)/Smad2/3 signaling pathway.
FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and
EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the
phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages
induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through
the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed
that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma
through FUT4/LeY- mediated fucosylation. Targeting this newly identified
signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.
PMID- 28423677
TI - Identifying the structure-activity relationship of leelamine necessary for
inhibiting intracellular cholesterol transport.
AB - Leelamine is an anticancer chemotherapeutic agent inhibiting intracellular
cholesterol transport. Cell death mediated by leelamine occurs due to the
lysosomotropic property of the compound, its accumulation in the lysosome, and
inhibition of cholesterol transport leading to lack of availability for key
processes required for functioning of cancer cells. The present study dissects
the structure-activity-relationship of leelamine using synthesized derivatives of
leelamine and abietic acid, a structurally similar compound, to identify the
moiety responsible for anti-cancer activity. Similar to leelamine, all active
derivatives had an amino group or a similar moiety that confers a lysosomotropic
property to the compound enabling its accumulation in the lysosome. Active
derivatives inhibited intracellular cholesterol transport and hindered
xenografted melanoma tumor development without obvious systemic toxicity. In
silico studies suggested that active derivatives accumulating in lysosomes bound
to NPC1, a protein responsible for cholesterol export from the lysosome, to
inhibit its activity that then caused accumulation, and lack of cholesterol
availability for other key cellular activities. Thus, active derivatives of
leelamine or abietic acid maintained lysosomotropic properties, bound to NPC1,
and disrupted cellular cholesterol transport as well as availability to retard
tumor development.
PMID- 28423678
TI - Influence of ipilimumab on expanded tumour derived T cells from patients with
metastatic melanoma.
AB - INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy
(ACT) is a promising treatment for patients with advanced melanoma. Retrospective
studies suggested an association between previous treatment with anti-CTLA-4
antibodies and long term survival after subsequent ACT. Thus, we hypothesized
that treatment with anti-CTLA-4 antibodies can induce favourable changes to be
detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had
a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG
3. In addition, broader and more frequent T cell responses against common tumour
antigens were detected in patients treated with Ipilimumab as compared to anti
CTLA-4 naive patients. MATERIALS AND METHODS: Expanded TILs were obtained from
patients with advanced melanoma who had received Ipilimumab in the previous six
months, or had not received any type of anti-CTLA-4 antibody. T cell specificity
and expression of phenotypic and exhaustion markers were scrutinized as well as
functional properties. CONCLUSIONS: Ipilimumab may induce tumor-infiltration of T
cells of a more naive phenotype expressing markers related to activation or
exhaustion. Additionally, Ipilimumab may increase the frequency of T cells
recognizing common tumour associated antigens.
PMID- 28423679
TI - Association of IL-1A and IL-1B polymorphisms with ankylosing spondylitis among
the Chinese Han population: a case-control study.
AB - Ankylosing spondylitis (AS) is a complex and chronic inflammatory disease with a
high heritage. Previous study has shown that IL-1A and IL-1B involved in
inflammatory reaction. But little is known about single nucleotide polymorphisms
(SNPs) of IL-1A and IL-1B associated with AS. We conducted a case-control study
among 267 AS cases and 297 healthy controls from China. In the genetic model
analysis, we found the "T" genotype of rs3783550 was associated with decreased AS
risk in the dominant model (p = 0.044) and log-additive model (p = 0.023); the
"C" genotype of rs3783546 was significantly associated with decreased AS risk
based in the dominant model (p = 0.044) and log-additive model (p = 0.023).
Additionally, the minor allele "A" of rs2853550 may also reduce the risk of AS in
dominant (p = 0.025) and log-additive model (p = 0.024). Our results suggested
that the polymorphisms of IL-1A and IL-1B are associated with the AS
susceptibility in the Chinese Han population. Further studies are needed to
characterize the functional sequences that cause AS.
PMID- 28423680
TI - A bioartificial dermal regeneration template promotes skin cell proliferation in
vitro and enhances large skin wound healing in vivo.
AB - A novel bioartificial dermal regeneration template has been developed using
platelet-rich plasma and acellular animal skin collagen sponge for the treatment
of larger area and full thickness skin wounds. This platelet-rich plasma-collagen
sponge keeps native skin structure and contains huge amounts of growth factors.
The effect of this bioartificial dermal regeneration template was tested in vitro
and in vivo via a mimic poor wound healing process by adding collagenase I into
cell culture medium or the wound area. The in vitro experimental results
indicated that the rat skin cells grew faster and produced more collagen in
platelet-rich plasma-collagen sponge with collagenase than those treated either
with collagen sponge plus collagenase, or collagenase, or control group without
treatment. The in vivo experiments were performed by large rat skin wounds, 1.5
cm diameter, treated either with collagenase, or collagenase plus collagen
sponge, or collagenase plus platelet-rich plasma-collagen sponge. The wound
without treatment was used as a control. The wounds treated with collagenase
containing platelet-rich plasma-collagen sponge healed 4 times faster than the
untreated wounds, 6 times faster than the collagenase treated wounds, 2.4 times
faster than collagenase-containing collagen sponge treated wounds. The
immunostaining indicated that the healed tissues in the wound areas treated with
collagenase-containing platelet-rich plasma-collagen sponge were composed of
collagen type I and collagen III with blood vessels and hair follicles. The
results demonstrated that this collagenase-containing platelet-rich plasma
collagen sponge works as a bioartificial dermal regeneration template. The
application of this collagenase-containing platelet-rich plasma-collagen sponge
promotes the traumatic skin wound healing and permits the reconstitution of the
inherent barrier functions of the skin.
PMID- 28423681
TI - Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism
targeted approach.
AB - The clinical course for both early and late stage Bladder Cancer (BC) continues
to be characterized by significant patient burden due to numerous occurrences and
recurrences requiring frequent surveillance strategies, intravesical drug
therapies, and even more aggressive treatments in patients with locally advanced
or metastatic disease. For these reasons, BC is also the most expensive cancer to
treat. Fortunately, BC offers an excellent platform for chemoprevention
interventions with potential to optimize the systemic and local exposure of
promising agents to the bladder mucosa. However, other than smoking cessation,
there is a paucity of research that systematically examines agents for
chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism
based approach, the goal of this review is to summarize epidemiological, in
vitro, and preclinical studies, including data regarding the safety,
bioavailability, and efficacy of agents evaluated for bladder cancer
chemoprevention. Based on the available studies, phytochemicals, specifically
isothiocyanates such as sulforaphane, present in Brassicaceae or "cruciferous"
vegetables in the precursor form of glucoraphanin are: (a) available in
standardized formulations; (b) bioavailable- both systemically and in the
bladder; (c) observed to be potent inhibitors of BC carcinogenesis through
multiple mechanisms; and (d) without toxicities at these doses. Based on
available evidence from epidemiological, in vitro, preclinical, and early phase
trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane
(SFN) represent a promising potential chemopreventitive agent in bladder cancer.
PMID- 28423682
TI - RIP3 deficiency ameliorates inflammatory response in mice infected with influenza
H7N9 virus infection.
AB - Influenza H7N9 virus infection causes an acute, highly contagious respiratory
illness that triggers cell death of infected cells and airway epithelial
destruction. RIP3 is a key regulator of cell death responses to a growing number
of viral and microbial agents. This study aimed to investigate the role of RIP3
in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-)
mice and littermate wild type mice were infected intranasally with influenza H7N9
virus (A/Fujian/S03/2015) to determine the contribution of RIP3 to the
inflammatory response of influenza H7N9 virus infection. It was found that RIP3-/
mice infected with H7N9 virus showed higher survival and less weight loss,
compared with wild type littermate mice. In addition, RIP3-/- mice had fewer
regions of edema, infiltration with inflammatory cells, and alvelolar collapses,
and the secretions of IL-1beta, IL-6, RANTES and MIP-1 in BALF were significantly
decreased on days 3 and 7 p.i. when compared with WT mice. Moreover, caspase
1/IL1beta signaling was found to be invovled in RIP3 associated imflammation of
influenza H7N9 virus, but not RIP3/MLKL dependent necrosis. In the conclusion,
our results indicated that RIP3 deficiency can protect mice from the infection of
influenza H7N9 virus by downregulating caspase 1/IL1beta signaling, which
provided edivence of the RIP3 invovled necroptosis independent manner.
PMID- 28423683
TI - The potential roles of aquaporin 4 in malignant gliomas.
AB - Aquaporin 4 (AQP4) is the major water channel expressed in the central nervous
system and is primarily expressed in astrocytes. Recently, accumulated evidence
has pointed to AQP4 as a key molecule that could play a critical role in glioma
development. Discoveries of the role of AQP4 in cell migration suggest that AQP4
could be a significant factor regarding glioma malignancies. However, the AQP4
expression levels in glioma have not been fully elucidated; furthermore, the
correlation of AQP4 expression with glioma malignancy remains controversial.
Here, we review the expression pattern and predictive significance of AQP4 in
malignant glioma. The molecular mechanism of AQP4 as it pertains to the migration
and invasion of human glioma cells has been summarized. In addition, the
important roles of AQP4 in combating drug resistance as well as potential
pharmacological blockers of AQP4 have been systematically discussed. More
research should be conducted to elucidate the potential roles of AQP4 in
malignant glioma for identifying the tumor type, progression stages and optimal
treatment strategies. The observed experimental results strongly emphasize the
importance of this topic for future investigations.
PMID- 28423685
TI - Tumor-fibroblast interactions stimulate tumor vascularization by enhancing
cytokine-driven production of MMP9 by tumor cells.
AB - Advance-stage breast carcinomas include significant amounts of fibroblasts and
infiltrating immune cells which have been implicated in tumor growth, recurrence,
and response to therapy. The present study investigated the contribution of
fibroblasts to tumor growth using direct tumor-fibroblast co-cultures and tumor
xenograft models. Our findings revealed that fibroblasts enhance breast carcinoma
growth by promoting the tumor vasculature via the MMP9-dependent mechanism. In
tumor-fibroblast co-cultures, fibroblasts increased expression of TGF-beta, TNF,
and IL-1beta cytokines in tumor cells. These cytokines cooperatively induced
expression of matrix metalloproteinase MMP9 in tumor cells. Knockdown of MMP9 by
shRNA significantly reduced tumor vascularization induced by fibroblasts.
Mechanistically, our findings argue that expression of MMP9 in tumor cellsis
regulated by crosstalk of TGF-beta with TNF and/or IL-1beta cytokines. The
mechanism of this cooperative response did not involve cross-activation of the
canonical signaling pathways as TGF-beta did not activate RELA/p65 signaling,
while TNF did not affect SMAD signaling. Instead, TGF-beta and TNF cytokines co
stimulated MAP kinases and expression of JUN and JUNB, AP1 transcription factor
subunits, which together with RELA/p65 were essential for the regulation of MMP9.
Depletion of JUN and JUNB or RELA in tumor cells blocked the cooperative
induction of MMP9 by the cytokines. Thus, our studies uncovered a previously
unappreciated role of tumor-fibroblast interactions in the stimulation of tumor
angiogenesis, and an essential role of the MAPK-AP1 axis in the cooperative up
regulation of the angiogenic driver MMP9 by cytokine crosstalk.
PMID- 28423688
TI - MicroRNAs in biofluids are novel tools for bladder cancer screening.
AB - MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in basic
cellular processes, including differentiation, proliferation, apoptosis and
autophagy. They are also involved in various stages of tumorigenesis and play key
roles in bladder cancer initiation and progression. Notably, the altered
expression of miRNAs in the tumors is reflected in body fluids, including blood
and urine, which opens avenues for non-invasive diagnosis and prognosis. Many
studies have demonstrated that epigenetic changes extensively alter tumoral
microRNA expression. The high reproducibility, specificity and sensitivity of
miRNA levels in body fluids suggest their potential use as biomarkers for cancer
screening and diagnosis. For example, recent technological advances have made it
possible to detect miRNAs in urine for bladder cancer screening. In this review,
we focus mainly on the current knowledge and future challenges for incorporating
miRNAs in body fluids, like urine and blood, for making clinical diagnoses and
assessing prognoses in bladder cancer.
PMID- 28423690
TI - PreImplantation factor (PIF) protects cultured embryos against oxidative stress:
relevance for recurrent pregnancy loss (RPL) therapy.
AB - Recurrent pregnancy loss (RPL) affects 2-3% of couples. Despite a detailed work
up, the etiology is frequently undefined, leading to non-targeted therapy. Viable
embryos and placentae express PreImplantation Factor (PIF). Maternal circulating
PIF regulates systemic immunity and reduces circulating natural killer cells
cytotoxicity in RPL patients. PIF promotes singly cultured embryos' development
while anti-PIF antibody abrogates it. RPL serum induced embryo toxicity is
negated by PIF. We report that PIF rescues delayed embryo development caused by
<3 kDa RPL serum fraction likely by reducing reactive oxygen species (ROS). We
reveal that protein disulfide isomerase/thioredoxin (PDI/TRX) is a prime PIF
target in the embryo, rendering it an important ROS scavenger. The 16F16-PDI/TRX
inhibitor drastically reduced blastocyst development while exogenous PIF
increased >2 fold the number of embryos reaching the blastocyst stage.
Mechanistically, PDI-inhibitor preferentially binds covalently to oxidized PDI
over its reduced form where PIF avidly binds. PIF by targeting PDI/TRX at a
distinct site limits the inhibitor's pro-oxidative effects. The >3kDa RPL serum
increased embryo demise by three-fold, an effect negated by PIF. However, embryo
toxicity was not associated with the presence of putative anti-PIF antibodies.
Collectively, PIF protects cultured embryos both against ROS, and higher
molecular weight toxins. Using PIF for optimizing in vitro fertilization embryos
development and reducing RPL is warranted.
PMID- 28423692
TI - The relationship between members of the canonical NF-kappaB pathway, components
of tumour microenvironment and survival in patients with invasive ductal breast
cancer.
AB - The aim of the present study was to examine the relationship between tumour NF
kappaB activation, tumour microenvironment including local inflammatory response
(LIR) and cancer-specific survival in patients with operable ductal breast
cancer.Immunohistochemistry (tissue microarray of 376 patients) and western
blotting (MCF7 and MDA-MB-231 breast cancer cells) was performed to assess
expression of key members of the canonical NF-kappaB pathway (inhibitory kappa B
kinase (IKKbeta) and phosphorylated p65 Ser-536 (p-p65)). Following silencing of
IKKbeta, cell viability and apoptosis was assessed in both MCF7 and MDA-MB-231
cell lines.P-p65 was associated with cancer-specific survival (CSS) (nuclear
P=0.042 and total P=0.025). High total p-p65 was associated with increase grade
tumour grade (P=0.010), ER positivity (P=0.023), molecular subtype (P=0.005),
lower Klintrup-Makinen grade (P=0.013) and decreased CD138 count (P=0.032). On
multivariate analysis, total p-p65 expression independently associated with
poorer CSS (P=0.020). In vitro work demonstrated that the canonical NF-kappaB
pathway was inducible by exposure to TNFalpha in ER-positive MCF7 cells and to a
lesser extent in ER-negative MDA-MB-231 cells. Reduction of IKKbeta expression by
siRNA transfection increased levels of apoptosis and reduced cell viability in
both MCF7 (P=<0.001, P=<0.001, respectively) and MDA-MB-231 cells (P=>0.001,
P=0.002, respectively). This is consistent with the hypothesis that canonical
IKKbeta-NF-kappaB signalling drives tumour survival.These results suggest that
activation of the canonical NF-kappaB pathway is an important determinant of poor
outcome in patients with invasive ductal breast cancer.
PMID- 28423693
TI - Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to
BAFF in treating human papillomavirus-associated cancer.
AB - B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that
not only stimulates B and T cells but also counteracts immune tolerance. BAFF is
also a type II membrane protein, which is secreted through the endoplasmic
reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance
the presentation of major histocompatibility complex class I molecules. These
characteristics represent an opportunity to enhance the antitumor effects of DNA
vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA
vaccine and evaluated its antitumor effects. We found that this vaccine increased
E7-specific CD8+ T-cell immune responses, engendered major antitumor effects
against E7-expressing tumors, and prolonged the survival of the immunized mice.
Interestingly, vaccinating B-cell-deficient mice with BAFF-E7 revealed
considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do
not contribute to this immune response. Image analysis through confocal
fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to
the ER, but not BAFF lacking 128 N-terminal residues that generated a lower
number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated
that the ER-targeting characteristic of BAFF is the main factor improving the
potency of DNA vaccines.
PMID- 28423694
TI - Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor
prognosis of head and neck carcinomas.
AB - BACKGROUND: Epstein-Barr virus (EBV) is the main cause of nasopharyngeal
carcinoma (NPC), also found in other head and neck carcinomas (HNSCCs) where its
role remains controversial. RESULTS: EBV was found in 80% and 21% of the samples
with PCR and ISH (in cancer cells), respectively. Eight of ISH-positive samples
were not NPCs. EBER-RNA detection in carcinoma cells was associated with worse
prognosis, whether or not NPCs were included. HPV/EBV and HSV/HPV coinfections
associated with a shorter survival. LMP-1 expression, positive in 51% of samples
did not correlate with the disease outcome. MATERIALS AND METHODS: We analyzed
EBV in 73 HNSCC samples with a known HPV and HSV-1 status, using in situ
hybridization (ISH) and immunohistochemistry (IHC) for EBV-early transcripts
(EBER) and LMP-1 protein, respectively. EBV-DNA was detected with a Luminex-based
method. The results were correlated with HPV-status and disease outcome.
CONCLUSIONS: EBV is transcriptionally active in NPC cells but also in a subgroup
of other HNSCCs.
PMID- 28423695
TI - NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the
mitochondria in breast cancer.
AB - Chemo-resistance presents a difficult challenge for the treatment of breast
cancer. Our previous study showed that N-Myc downstream-regulated gene 2 (NDRG2)
is involved in p53-mediated apoptosis induced by chemotherapy, through a
mechanism that has so far remained obscure. Here, we explored the role of NDRG2
in chemo-resistance with a focus on Adriamycin (ADR) and found that NDRG2
expression decreased in ADR resistance breast cancer cells. Interestingly, NDRG2
can promote ADR sensitivity by inhibiting proliferation, enhancing cellular
damage responses, and promoting apoptosis in a p53-dependent manner. We also
found that NDRG2 could upregulate Bad expression by increasing its half-life,
which is associated with p53 to mitochondria. Hence, our collective data provided
the first evidence that NDRG2 promoting sensitivity of breast cancer is dependent
on p53 by preventing p53 from entering the nucleus rather than changing its
expression.
PMID- 28423696
TI - Improvement of dexamethasone sensitivity by chelation of intracellular Ca2+ in
pediatric acute lymphoblastic leukemia cells through the prosurvival kinase
ERK1/2 deactivation.
AB - Previous studies have demonstrated that glucocorticoid hormones, including
dexamethasone, induced alterations in intracellular calcium homeostasis in acute
lymphoblastic leukemia (ALL) cells. However, the mechanism by which intracellular
calcium homeostasis participates in dexamethasone sensitivity and resistance on
ALL cells remains elusive. Here, we found that treatment of cells with
dexamethasone resulted in increased intracellular calcium concentrations through
store-operated calcium entry stimulation, which was curtailed by store-operated
calcium channel blockers. We show that BAPTA-AM, an intracellular Ca2+ chelator,
synergistically enhances dexamethasone lethality in two human ALL cell lines and
in three primary specimens. This effect correlated with the inhibition of the
prosurvival kinase ERK1/2 signaling pathway. Chelating intracellular calcium with
Bapta-AM or inhibiting ERK1/2 with PD98059 significantly potentiated
dexamethasone-induced mitochondrial membrane potential collapse, reactive oxygen
species production, cytochrome c release, caspase-3 activity, and cell death.
Moreover, we show that thapsigargin elevates intracellular free calcium ion
level, and activates ERK1/2 signaling, resulting in the inhibition of
dexamethasone-induced ALL cells apoptosis. Together, these results indicate that
calcium-related ERK1/2 signaling pathway contributes to protect cells from
dexamethasone sensitivity by limiting mitochondrial apoptotic pathway. This
report provides a novel resistance pathway underlying the regulatory effect of
dexamethasone on ALL cells.
PMID- 28423697
TI - Essential role of endogenous prolactin and CDK7 in estrogen-induced upregulation
of the prolactin receptor in breast cancer cells.
AB - Our early studies have shown that Estradiol (E2)/Estrogen Receptor alpha (ER) in
a non-DNA dependent manner through complex formation with C/EBPbeta/SP1 induced
transcriptional activation of the generic hPIII promoter and expression of the
Prolactin Receptor (PRLR) receptor in MCF-7 cells. Subsequent studies
demonstrated effects of unliganded ERalpha with requisite participation of
endogenous PRL on the activation of PRLR transcription. Also, EGF/ERBB1 in the
absence of PRL and E2 effectively induced upregulation of the PRLR. In this study
we have delineated the transcriptional mechanism of upregulation of PRLR receptor
induced by E2 incorporating knowledge of the various transcriptional upregulation
modalities from our previous studies. Here, we demonstrate an essential
requirement of STAT5a induced by PRL via PRLR receptor which associates at the
promoter and its interaction with phoshoERalpha S118. Knock-down of PRL by siRNA
significantly reduced E2-induced PRLR promoter activity, mRNA and protein
expression, recruitment of ERalpha to the complex at promoter, C/EBPbeta
association to its DNA site and productive complex formation at hPIII promoter.
The specific CDK7 inhibitor (THZ1) that attenuates E2-induced ERalpha
phosphorylation at S118 abrogated E2-induced PRLR promoter activation. Further
studies demonstrated that E2 induced cell migration was inhibited by PRL siRNA
and THZ1 indicating its dependence on PRL/PRLR and CDK7, respectively. Our
studies have demonstrated the essential role of endogenous PRL and CDK7 in the
upregulation of PRLR by E2 and provide insights for therapeutic approaches that
will mitigate the transcription/expression of PRLR and its participation in
breast cancer progression fueled by E2 and PRL via their cognate receptors.
PMID- 28423698
TI - Parameters of simultaneous 18F-FDG-PET/MRI predict tumor stage and several
histopathological features in uterine cervical cancer.
AB - The purpose of this study was to analyze associations between apparent diffusion
coefficient (ADC) and standardized uptake values (SUV) values and different
histopathological parameters in uterine cervical cancer. 21 patients with primary
uterine cervical cancer were involved into the study. All patients underwent a
whole body simultaneous18F-FDG PET/MRI. Mean and maximum SUV were noted (SUVmean
and SUVmax). In all tumors minimal, mean, and maximal ADC values (ADCmin,
ADCmean, and ADCmax) were estimated. Combined parameters were calculated:
SUVmax/SUVmean, ADCmin/ ADCmean, SUVmax/ADCmin and SUVmax/ADCmean. In all cases
the diagnosis was confirmed histopathologically by tumor biopsy. Histological
slices were stained by hematoxilin and eosin, MIB 1 monoclonal antibody, and p16.
All histopathological images were digitalized and analyzed by using a ImageJ
software 1.48v. The following parameters were estimated: cell count,
proliferation index KI 67, total and average nucleic areas, epithelial and
stromal areas. Spearman's correlation coefficient was used to analyze
associations between ADC and SUV values and histological parameters. P values <=
0.05 were considered as statistically significant. ADCmin and ADCmin/ ADCmean
were statistically significant lower in N positive tumors. KI 67 correlated
statistically significant with SUVmax (r = 0.59, p = 0.005), SUVmean (0.45, p =
0.04), ADCmin (r = -0.48, p = 0.03), SUVmax/ADCmin (r = 0.71, p = 0.001),
SUVmax/ADCmean (0.75, p = 0.001). SUVmax correlated well with epithelial area (r
= 0.71, p = 0.001) and stromal areas (r = -0.71, p = 0.001). SUV values, ADCmin,
SUVmax/ADCmin and SUVmax/ADCmean correlated statistically significant with KI 67
and can be used to estimate the proliferation potential of tumors. SUV values
correlated strong with epithelial area of tumor reflected metabolic active areas.
PMID- 28423699
TI - Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small
lung cancer and regulates cell proliferation via epigenetically repressing p21
and p57 expression.
AB - Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key
roles in regulating cellular processes, such as proliferation, invasion, and
metastasis. These lncRNAs have been shown to be abnormally expressed in
tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non
small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the
expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to
non-tumor tissues, and its expression was associated with tumor size, tumor-node
metastasis (TNM) stage and overall survival (OS). Further experiments showed that
LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo.
Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest.
We further demonstrated that LUCAT1 was associated with polycomb repressor
complexes (PRC2) and that this association was required for epigenetically
repression of p21 and p57, thus contributing to the regulation of NSCLC cell
cycle and proliferation. In summary, our results show that LUCAT1 could regulate
tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.
PMID- 28423700
TI - HLA class I loss in metachronous metastases prevents continuous T cell
recognition of mutated neoantigens in a human melanoma model.
AB - T lymphocytes against tumor-specific mutated neoantigens can induce tumor
regression. Also, the size of the immunogenic cancer mutanome is supposed to
correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied
the susceptibility of tumor cell lines from lymph node metastases occurring in a
melanoma patient over several years towards blood-derived, neoantigen-specific
CD8+ T cells. In contrast to a cell line established during early stage III
disease, all cell lines generated at later time points from stage IV metastases
exhibited partial or complete loss of HLA class I expression. Whole exome and
transcriptome sequencing of the four tumor lines and a germline control were
applied to identify expressed somatic single nucleotide substitutions (SNS),
insertions and deletions (indels). Candidate peptides encoded by these variants
and predicted to bind to the patient's HLA class I alleles were synthesized and
tested for recognition by autologous mixed lymphocyte-tumor cell cultures
(MLTCs). Peptides from four mutated proteins, HERPUD1G161S, INSIG1S238F,
MMS22LS437F and PRDM10S1050F, were recognized by MLTC responders and MLTC-derived
T cell clones restricted by HLA-A*24:02 or HLA-B*15:01. Intracellular peptide
processing was verified with transfectants. All four neoantigens could only be
targeted on the cell line generated during early stage III disease. HLA loss
variants of any kind were uniformly resistant. These findings corroborate that,
although neoantigens represent attractive therapeutic targets, they also
contribute to the process of cancer immunoediting as a serious limitation to
specific T cell immunotherapy.
PMID- 28423701
TI - Identification of protein clusters predictive of tumor response in rectal cancer
patients receiving neoadjuvant chemo-radiotherapy.
AB - Preoperative neoadjuvant chemoradiotherapy (nCRT) is the gold standard in locally
advanced rectal cancer, only 10-30% of patients achieving benefits. Currently,
there is a need of a reliable selection of markers for the identification of poor
or non-responders prior to therapy. In this work, we compared protein profiles
before therapy of patients differing in their responses to nCRT to find novel
predictive markers of response to therapy. Patients were grouped into 3 groups
according to their tumor regression grading (TRG) after surgery: 'TRG 1-2', good
responders, 'TRG 3' and 'TRG 4', poor responders. Paired surgical specimens of
rectal cancer and healthy (histologically confirmed) rectal tissues from 15
patients were analysed before nCRT by two dimensional difference in gel
electrophoresis followed by mass spectrometry. Thirty spots were found as
differentially expressed (p < 0.05). Among them, 3 spots (spots 471, 683 and 684)
showed an increased amount of protein in poor responders compared with good
responders, and they were more tumor associated compared with healthy tissues.
Proteins of these spots were identified as fibrinogen beta chain fragment D,
actin isoforms, B9 and B5 serpins, cathepsin D isoforms and peroxiredoxin-4. In
an independent validation set of 20 rectal carcinomas we validated the increased
fibrinogen beta chain abundance before nCRT in poor responders by immunoblotting.
In conclusion, we propose a risk-stratification tool in predicting the response
to nCRT treatment in rectal cancer based on the quantity of these proteins.
PMID- 28423702
TI - Experience with precision genomics and tumor board, indicates frequent target
identification, but barriers to delivery.
AB - BACKGROUND: The ability to analyze the genomics of malignancies has opened up new
possibilities for off-label targeted therapy in cancers that are refractory to
standard therapy. At Mayo Clinic these efforts are organized through the Center
for Individualized Medicine (CIM). RESULTS: Prior to GTB, datasets were analyzed
and integrated by a team of bioinformaticians and cancer biologists.
Therapeutically actionable mutations were identified in 65% (92/141) of the
patients tested with 32% (29/92) receiving genomically targeted therapy with FDA
approved drugs or in an independent clinical trial with 45% (13/29) responding.
Standard of care (SOC) options were continued by 15% (14/92) of patients tested
before exhausting SOC options, with 71% (10/14) responding to treatment. Over 35%
(34/92) of patients with actionable targets were not treated with 65% (22/34)
choosing comfort measures or passing away. MATERIALS AND METHODS: Patients (N =
165) were referred to the CIM Clinic between October 2012 and December 2015. All
patients received clinical genomic panel testing with selected subsets receiving
array comparative genomic hybridization and clinical whole exome sequencing to
complement and validate panel findings. A genomic tumor board (GTB) reviewed
results and, when possible, developed treatment recommendations. CONCLUSIONS:
Treatment decisions driven by tumor genomic analysis can lead to significant
clinical benefit in a minority of patients. The success of genomically driven
therapy depends both on access to drugs and robustness of bioinformatics
analysis. While novel clinical trial designs are increasing the utility of
genomic testing, robust data sharing of outcomes is needed to optimize clinical
benefit for all patients.
PMID- 28423703
TI - Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent
apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer
cells.
AB - Artocarpin has been shown to exhibit cytotoxic effects on different cancer cells,
including non-small cell lung carcinoma (NSCLC, A549). However, the underlying
mechanisms remain unclear. Here, we explore both p53-dependent and independent
apoptosis pathways in artocarpin-treated NSCLC cells. Our results showed that
artocarpin rapidly induced activation of cellular protein kinases including
Erk1/2, p38 and AktS473. Inhibition of these protein kinases prevented artocarpin
induced cell death. Moreover, artocarpin-induced phosphorylation of these protein
kinases and apoptosis were mediated by induction of reactive oxygen species
(ROS), as pretreatment with NAC (a ROS scavenger) and Apocynin (a Nox-2
inhibitor) blocked these events. Similarly, transient transfection of p47Phox or
p91Phox siRNA attenuated artocarpin-induced NADPH oxidase activity and cell
death. In addition, p53 dependent apoptotic proteins including PUMA, cytochrome
c, Apaf-1 and caspase 3 were activated by artocarpin, and these effects can be
abolished by antioxidants, MAPK inhibitors (U0126 and SB202190), but not by PI3K
inhibitor (LY294002). Furthermore, we found that artocarpin-induced Akt
phosphorylation led to increased NF-kappaB activity, which may act as an upstream
regulator in the c-Myc and Noxa pathway. Therefore, we propose that enhancement
of both ERK/ p38/ p53-dependent or independent AktS473/NF-kappaB/c-Myc/Noxa
cascade by Nox-derived ROS generation plays an important role in artocarpin
induced apoptosis in NSCLC cells.
PMID- 28423704
TI - Prognostic and clinicopathological role of long non-coding RNA UCA1 in various
carcinomas.
AB - Urothelial cancer associated 1 (UCA1) as an oncogenic long non-coding RNA
(LncRNA) was aberrantly upregulated in various solid tumors. Numerous studies
have demonstrated overexpression of UCA1 is an unfavorable prognostic indicator
in cancer patients. This study aimed to further explore the prognosis role and
clinical significance of UCA1 in cancer. Eligible studies were recruited by a
systematic search in PubMed, Embase, Cochrane Library and Web of Science
databases. A total of 19/16 studies with 1587/1291 cancer patients were included
to evaluate the association between UCA1 expression and overall survival (OS) and
clinicopathological factors of malignancies by computing hazard ratio (HR), odds
ratios (OR) and confidence interval (CI). The meta-analysis indicated
overexpression of UCA1 was significantly correlated with unexpected OS in
patients with cancer (pooled HR = 1.85, 95% CI 1.62-2.10, p < 0.001). There was
also a significantly negative association between high level of UCA1 and poor
grade cancer (pooled OR = 2.74, 95% CI 2.04-3.70, p < 0.001) and positive
lymphatic metastasis (pooled OR = 2.43, 95% CI 1.72-3.41, p < 0.001). In
conclusion, our study suggested that UCA1 was correlated with more advanced
clinicopathological features and poor prognosis as a novel predictive biomarker
of patients with various tumors.
PMID- 28423706
TI - Identification of Ras suppressor-1 (RSU-1) as a potential breast cancer
metastasis biomarker using a three-dimensional in vitro approach.
AB - Breast cancer (BC) is the most common malignant disease in women, with most
patients dying from metastasis to distant organs, making discovery of novel
metastasis biomarkers and therapeutic targets imperative. Extracellular matrix
(ECM)-related adhesion proteins as well as tumor matrix stiffness are important
determinants for metastasis. As traditional two-dimensional culture does not take
into account ECM stiffness, we employed 3-dimensional collagen I gels of
increasing concentration and stiffness to embed BC cells of different
invasiveness (MCF-7, MDA-MB-231 and MDA-MB-231-LM2) or tumor spheroids. We tested
the expression of cell-ECM adhesion proteins and found that Ras Suppressor-1 (RSU
1) is significantly upregulated in increased stiffness conditions. Interestingly,
RSU-1 siRNA-mediated silencing inhibited Urokinase Plasminogen Activator, and
metalloproteinase-13, whereas tumor spheroids formed from RSU-1-depleted cells
lost their invasive capacity in all cell lines and stiffness conditions. Kaplan
Meier survival plot analysis corroborated our findings showing that high RSU-1
expression is associated with poor prognosis for distant metastasis-free and
remission-free survival in BC patients. Taken together, our results indicate the
important role of RSU-1 in BC metastasis and set the foundations for its
validation as potential BC metastasis marker.
PMID- 28423707
TI - Tropomyosin-related kinase B mediated signaling contributes to the induction of
malignant phenotype of gallbladder cancer.
AB - This study aims to demonstrate the clinical and biological significance of Brain
derived neurotrophic factor (BDNF)/Tropomyosin-related kinase B (TrkB) signaling
in gallbladder cancer (GBC) through a series of in vitro and in vivo experiments.
TrkB expression was detected in 63 (91.3%) out of 69 surgically resected primary
GBC specimens by immunohistochemistry. TrkB expression in the invasive front
correlated with T factor (p=0.0391) and clinical staging (p=0.0391). Overall
survival was lower in patients with high TrkB expression in the invasive front
than in those with low TrkB expression (p=0.0363). In vitro experiment, we used
five TrkB-expressing GBC cell lines with or without K-ras mutation. TrkB-mediated
signaling increased proliferation and the invasiveness by inducing epithelial
mesenchymal transition, and activating matrix metalloproteinases-2 (MMP-2) and
MMP-9. Inhibition of TrkB-mediated signaling also decreased hypoxia-inducible
factor-1alpha, vascular endothelial growth factor A (VEGF-A), VEGF-C, and VEGF-D
expression. In vivo experiment, inhibition of TrkB-mediated signaling suppressed
tumorigenicity and tumor growth in GBC. These findings demonstrate that TrkB
mediated signaling contributes to the induction of malignant phenotypes
(proliferation, invasiveness, angiogenesis, lymphangiogenesis, and tumorigenesis)
in GBC, and could be a promising therapeutic target regardless of K-ras mutation
status.
PMID- 28423709
TI - Prognostic values of clinicopathological characteristics and survival outcomes in
prostate infiltrating ductal carcinoma: a population-based study.
AB - Infiltrating ductal carcinoma (IDC) is a rare histologic subtype of prostate
cancer. We investigated the clinicopathological features and prognosis of IDC
compared with acinar cell carcinoma (ACC). We identified 3814 men diagnosed with
prostate cancer between 2004 to and 2013 in the Surveillance, Epidemiology, and
End Results database, including 511 IDC and 3303 ACC cases. Prostate cancer
specific survival (PCSS) was compared using univariate and multivariate Cox
proportional hazards models. Generally, IDC occurred in older men (>= 65 years
old) and presented with larger sizes, and higher grades, American Joint Committee
on Cancer (AJCC) stages, AJCC T stages, lymph node positive rates and metastasis
rates. Men with IDC were less likely to undergo radical prostatectomy, but more
likely to be treated with adjuvant radiation than men with ACC. Five-year PCSS
rates were significantly worse in IDC. In the multivariate analysis, patients
with ACC had a better PCSS than patients with IDC. In conclusion, IDC has unique
clinicopathological characteristics and has worse prognosis than ACC.
Multivariable Cox regression analysis showed that age over 85 years, higher grade
and T stage, and metastasis at diagnosis were independent prognostic factors of
worse survival outcomes, whereas radical prostatectomy was an independent
prognostic factor of better survival outcomes.
PMID- 28423708
TI - Targeting the centriolar replication factor STIL synergizes with DNA damaging
agents for treatment of ovarian cancer.
AB - Advanced ovarian cancer is an incurable disease. Thus, novel therapies are
required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA
screen performed in 42 ovarian cancer cell lines identified the centriolar
replication factor STIL as an essential gene for ovarian cancer cells. This was
verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion
by administration of siRNA in neutral liposomes resulted in robust anti-tumor
effect that was further enhanced in combination with cisplatin. Consistent with
this finding, STIL depletion enhanced the extent of DNA double strand breaks
caused by DNA damaging agents. This was associated with centrosomal depletion,
ongoing genomic instability and enhanced formation of micronuclei. Interestingly,
the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we
observed that depletion of STIL enhanced canonical homologous recombination
repair and increased BRCA1 and RAD51 foci in response to DNA double strand
breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA
damaging chemotherapeutic drugs in treatment of ovarian cancer.
PMID- 28423710
TI - Phospholipase Cdelta1 suppresses cell migration and invasion of breast cancer
cells by modulating KIF3A-mediated ERK1/2/beta- catenin/MMP7 signalling.
AB - Phospholipase C delta1 (PLCD1) encodes an enzyme involved in energy metabolism,
calcium homeostasis and intracellular movement. It is located at 3p22 in a region
that is frequently deleted in multiple cancers, and the PLCD1 enzyme is a
potential tumour suppressor in breast cancer that inhibits matrix metalloprotease
(MMP) 7, but the detailed mechanism remains elusive. In this study, we found that
PLCD1 was downregulated in breast cancers, and the gain-or-loss functional assay
revealed that PLCD1 inhibited cell migration and invasion in vitro via the
ERK1/2/beta-catenin/MMP7 signalling pathway. Furthermore, KIF3A was identified as
a downstream mediator of PLCD1, and there was an inverse correlation between the
expression of PLCD1 and KIF3A. Knockdown of KIF3A expression alone suppressed
cell migration and invasion, and attenuated ERK1/2/beta-catenin/MMP7 signalling
that was reactivated by knocking down PLCD1 in vitro. Collectively, our findings
suggest that PLCD1 acts as a tumour suppressor, by KIF3A-mediated suppression of
ERK1/2/beta-catenin/MMP7 signalling, at least in part, in breast cancer.
PMID- 28423711
TI - The antitumor activity and preliminary modeling on the potential mechanism of
action of human peroxiredoxin-5.
AB - Goat peroxiredoxin-5 (gPRDX5) was verified as a good anti-cancer bioactive
peptide (ACBP) against different tumor cell lines. Considering the immunogenicity
between species for further therapeutic application, it is necessary to similarly
investigate the antitumor activity of human peroxiredoxin-5 (hPRDX5) with 89%
similarity in sequence to gPRDX5. In order to evaluate its antitumor activity,
the potential anti-neoplastic effect of hPRDX5 on a mouse model was observed
directly. The results of its in vivo antitumor activity suggested that hPRDX5
could resist immunosuppression by promoting lymphocyte proliferation and up
regulating the levels of serum cytokines. Meanwhile, PD-L1 was speculated as one
of the targets of hPRDX5 to inhibit tumor by enhancing the immune activity
according to a preliminary molecular docking study on the interactions between
hPRDX5 and PD-L1. The modeling provides a basis for structural modification on
hPRDX5/PD-L1 for further biological and biochemical study on the pathway blocking
mechanism of hPRDX5. In this work, the results demonstrate that hPRDX5 displays
efficient antitumor and immunoregulatory properties in the colon cancer
C26/BALB/c and melanoma B16/C57Bl/6 mice tumor models, and suggest the potential
of developing peptides from hPRDX5 as low molecular weight drug candidates for
corresponding cancer immunotherapy.
PMID- 28423712
TI - Model-based unsupervised learning informs metformin-induced cell-migration
inhibition through an AMPK-independent mechanism in breast cancer.
AB - We demonstrate that model-based unsupervised learning can uniquely discriminate
single-cell subpopulations by their gene expression distributions, which in turn
allow us to identify specific genes for focused functional studies. This method
was applied to MDA-MB-231 breast cancer cells treated with the antidiabetic drug
metformin, which is being repurposed for treatment of triple-negative breast
cancer. Unsupervised learning identified a cluster of metformin-treated cells
characterized by a significant suppression of 230 genes (p-value < 2E-16). This
analysis corroborates known studies of metformin action: a) pathway analysis
indicated known mechanisms related to metformin action, including the citric acid
(TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value <
1E-9); b) 70% of these 230 genes were functionally implicated in metformin
response; c) among remaining lesser functionally-studied genes for metformin
response was CDC42, down-regulated in breast cancer treated with metformin.
However, CDC42's mechanisms in metformin response remained unclear. Our
functional studies showed that CDC42 was involved in metformin-induced inhibition
of cell proliferation and cell migration mediated through an AMPK-independent
mechanism. Our results points to 230 genes that might serve as metformin response
signatures, which needs to be tested in patients treated with metformin and,
further investigation of CDC42 and AMPK-independence's role in metformin's
anticancer mechanisms.
PMID- 28423713
TI - Systematic analysis of gene expression alterations and clinical outcomes of
adenylate cyclase-associated protein in cancer.
AB - Adenylate Cyclase-associated protein (CAP) is an evolutionarily conserved protein
that regulates actin dynamics. Our previous study indicates that CAP1 is
overexpressed in NSCLC tissues and correlated with poor clinical outcomes, but
CAP1 in HeLa cells actually inhibited migration and invasion, the role of CAP was
discrepancy in different cancer types. The present study aims to determine
whether CAP can serve as a prognostic marker in human cancers. The CAP expression
was assessed using Oncomine database to determine the gene alteration during
carcinogenesis, the copy number alteration, or mutations of CAP using cBioPortal,
International Cancer Genome Consortium, and Tumorscape database investigated, and
the association between CAP expression and the survival of cancer patient using
Kaplan-Meier plotter and PrognoScan database evaluated. Therefore, the functional
correlation between CAP expression and cancer phenotypes can be established;
wherein CAP might serve as a diagnostic marker or therapeutic target for certain
types of cancers.
PMID- 28423714
TI - Usefulness of the MRP2 promoter to overcome the chemoresistance of
gastrointestinal and liver tumors by enhancing the expression of the drug
transporter OATP1B1.
AB - Tumor response to chemotherapy is often limited by drug export through ABC
proteins. To overcome this problem, here we have investigated the usefulness of
inducing the expression of the multidrug uptake transporter OATP1B1 under the
control of the MRP2 promoter (MRP2pr). Human hepatoma cells (Alexander) were
transfected with MRP2pr fragments of different length fused to the firefly
luciferase ORF in order to select the shortest fragment with the highest response
to dexamethasone, which was subsequently used to generate the chimeric construct
MRP2pr-OATP1B1-V5. Hepatoma cells transduced with MRP2pr-OATP1B1-V5 resulted in
dexamethasone-sensitive inducible OATP1B1 expression and enhanced selective
antitumor response to OATP1B1 substrates (paclitaxel, Bamet-R2 and Bamet-UD2). In
human colon cancer cells LS174T/R, used as a model of endogenous chemoresistance
due to MRP2 overexpression, MRP2pr-OATP1B1 induced OATP1B1 expression together
with chemosensitivity to OATP1B1 substrates. In nude mice, xenografted tumors
formed by LS174T/R cells transduced with MRP2pr-OATP1B1 plus treatment with
dexamethasone were markedly sensitized to Bamet-UD2. In conclusion, the induced
expression of anticancer drug uptake transporters, under the control of promoters
of ABC proteins involved in chemoresistance, constitutes an interesting approach
to overcome the poor response of cancer to chemotherapy due to reduced drug
uptake and/or enhanced drug export.
PMID- 28423715
TI - A functional variant at the miRNA binding site in HMGB1 gene is associated with
risk of oral squamous cell carcinoma.
AB - Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally
associated with both hereditary and acquired factors. The high mobility group box
1 (HMGB1) gene plays an important role as a DNA chaperone to help maintain
nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide
range of pathological processes, including inflammation and cancer. The present
study explores the impact of HMGB1 gene polymorphisms, combined with
environmental risks regarding susceptibility to oral tumorigenesis. Four single
nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825,
rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772
patients with OSCC. We found an association between the wild-type allele of
rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and
AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics
analysis was used to characterize the functional relevance of these variants for
the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3'-UTR
and promoter regions. Moreover, in considering behavioral exposure to
environmental carcinogens, the presence of the four HMGB1 SNPs, combined
with/without betel quid chewing and smoking showed, profoundly synergistic
effects on the risk of OSCC. In conclusion, we present a potential clinical
relevance for HMGB1 variants in OSCC, as well as associations between HMGB1
polymorphisms, haplotypes and environmental risk factors. The finding may help in
development of optimal therapeutic approaches for OSCC patients.
PMID- 28423716
TI - Oncogenic features of neuromedin U in breast cancer are associated with NMUR2
expression involving crosstalk with members of the WNT signaling pathway.
AB - Neuromedin U (NMU) has been shown driving the progression of various tumor
entities, including breast cancer. However, the expression pattern of NMU and its
receptors in breast cancer tissues as well as systematic insight into mechanisms
and downstream targets of the NMU-driven signaling pathways are still elusive.
Here, NMU expression was found up-regulated in all breast cancer subtypes when
compared to healthy breast tissue. Using an in silico dataset comprising 1,195
samples, high NMU expression was identified as an indicator of poor outcome in
breast tumors showing strong NMUR2 expression. Next, the biological impact of NMU
on breast cancer cells in relation to NMUR2 expression was analyzed. Ectopic NMU
expression reduced colony growth while promoting a motile phenotype in NMUR2
positive SKBR3 but not NMUR2-negative Hs578T cells. To uncover signaling pathways
and key molecules affected by NMU in SKBR3 cells, Affymetrix microarray analysis
was applied. Forced NMU expression affected molecules involved in WNT receptor
signaling among others. As such we demonstrated enhanced activation of the
WNT/planar cell polarity (PCP) effector RAC1 and down-regulation of canonical WNT
targets such as MYC. In summary, NMU might contribute to progression of NMUR2
positive breast cancer representing a potential druggable target for future
personalized strategies.
PMID- 28423717
TI - Non-homologous end joining induced alterations in DNA methylation: A source of
permanent epigenetic change.
AB - In addition to genetic mutations, epigenetic revision plays a major role in the
development and progression of cancer; specifically, inappropriate DNA
methylation or demethylation of CpG residues may alter the expression of genes
that promote tumorigenesis. We hypothesize that DNA repair, specifically the
repair of DNA double strand breaks (DSB) by Non-Homologous End Joining (NHEJ) may
play a role in this process. Using a GFP reporter system inserted into the genome
of HeLa cells, we are able to induce targeted DNA damage that enables the cells,
after successfully undergoing NHEJ repair, to express WT GFP. These GFP+ cells
were segregated into two expression classes, one with robust expression (Bright)
and the other with reduced expression (Dim). Using a DNA hypomethylating drug
(AzadC) we demonstrated that the different GFP expression levels was due to
differential methylation statuses of CpGs in regions on either side of the break
site. Deep sequencing analysis of this area in sorted Bright and Dim populations
revealed a collection of different epi-alleles that display patterns of DNA
methylation following repair by NHEJ. These patterns differ between Bright and
Dim cells which are hypo- and hypermethylated, respectively, and between the post
repair populations and the original, uncut cells. These data suggest that NHEJ
repair facilitates a rewrite of the methylation landscape in repaired genes,
elucidating a potential source for the altered methylation patterns seen in
cancer cells, and understanding the mechanism by which this occurs could provide
new therapeutic targets for preventing this process from contributing to
tumorigenesis.
PMID- 28423718
TI - iTRAQ-based quantitative proteomic analysis of Yamanaka factors reprogrammed
breast cancer cells.
AB - Cancer cells had been developed to be reprogrammed into embryonic stem like cells
by induced pluripotent stem cells (iPSCs) technology, however, the tumor
differentiation/dedifferentiation mechanisms had not yet been analyzed on a
genome-wide scale. Here, we inserted the four stem cell transcription factor
genes OCT4, SOX2, C-MYC and KLF4 into MCF cells (MCFs), represented a female
breast cancer cell type, and obtained iPSCs (Mcfips) in about 3 weeks. By using
the LC MS/MS iTRAQ technology, we analyzed the proteomic changes between MCFs and
Mcfips. Of identified 4,616 proteins totally, 247 and 142 differentially
expressed (DE) proteins were found in Mcfips compared with human induce
pluripotent stem cells (Hips) and MCFs, respectively. 35 co-up and 10 co-down
regulated proteins were recognized in DE proteins. Above DE proteins were
categorized with GO functional classification annotation and KEGG metabolic
pathway analysis into biological processes. In the protein interaction network,
we found 37 and 39 hubs interacted with more than one protein in Mcfips comparing
to Hips, in addition, 25 and 9 hubs were identified in Mcfips comparing to MCFs.
Importantly, the mitochondria, ribosome and tumor suppressor proteins were found
to be core regulators of tumor reprogramming, which might contribute to
understand the mechanisms in relation to the occurrences and progression of a
tumor. Thus, our study provided a valuable data for exploring the possibility to
normalize the malignant phenotype.
PMID- 28423719
TI - AMPKalpha phosphatase Ppm1E upregulation in human gastric cancer is required for
cell proliferation.
AB - Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer
strategy. In the current study, we tested expression and potential function of
Ca2+/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKalpha
phosphatase, in human gastric cancers. Ppm1E expression was elevated in human
gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p
AMPKalpha, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation.
Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in
human gastric cancer cell lines (AGS, HGC-27, and SNU601). Intriguingly, Ppm1E
knockdown by shRNA induced AMPK activation, mTORC1 inactivation, and
proliferation inhibition in AGS cells. On the other hand, forced over-expression
of Ppm1E induced further AMPK inhibition and mTORC1 activation to enhance AGS
cell proliferation. Remarkably, microRNA-135b-5p ("miR-135b-5p"), an anti-Ppm1E
microRNA, was downregulated in both human gastric cancer tissues and cells.
Reversely, miR-135b-5p exogenous expression caused Ppm1E depletion, AMPK
activation, and AGC cell proliferation inhibition. Together, Ppm1E upregulation
in human gastric cancer is important for cell proliferation, possible via
regulating AMPK-mTOR signaling.
PMID- 28423720
TI - Meta-analysis of oxaliplatin-based versus fluorouracil-based neoadjuvant
chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer.
AB - A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil
based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally
advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched
for relevant randomized controlled trials (RCTs) until January 31 2017. Review
Manager (version 5.3) was used to analyze the data. Dichotomous data were
calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8
RCTs with 6103 stage II or III rectal cancer patients were analyzed, including
2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with
fluorouracil alone regimen. Compared with fluorouracil-based regimen group,
oxaliplatin-based regimen group attained higher pathologic complete response (OR
= 1.29, 95% CI: 1.12-1.49, P = 0.0005) and 3-year disease-free survival (OR =
1.15, 95% CI: 0.93-1.42, P = 0.21), but suffered greater toxicity (OR = 2.07, 95%
CI: 1.52-2.83, P < 0.00001). Also, there were no significant differences between
two regimens in sphincter-sparing surgery rates (OR = 0.94, 95% CI: 0.83-1.06, P
= 0.33), 5-year disease-free survival (OR = 1.15, 95% CI: 0.93-1.42, P = 0.21)
and overall survival (3-year, OR = 1.14, 95% CI: 0.98-1.34, P = 0.09; 5-year, OR
= 1.06, 95% CI: 0.78-1.44, P = 0.70). In conclusion, the benefits of adding
oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant
chemotherapy for locally advanced rectal cancer remains controversial, and cannot
be considered a standard approach.
PMID- 28423721
TI - Downregulation of phosphorylated MKK4 is associated with a poor prognosis in
colorectal cancer patients.
AB - Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N
terminal kinase signaling and influences malignant metastasis. Here, we used
immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine
their association with the clinicopathological features of a pilot set of patient
samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and
colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation
set of CRC cases with accompanying follow-up data to confirm their
clinicopathological and prognostic significance. pMKK4 levels, which were high in
79.17% of NCM samples, were downregulated in 33.33% of CA and 63.54% of CRC
samples. pMKK4 downregulation was associated with metastasis, especially to the
liver. In the validation set, pMKK4 downregulation was associated with increases
in invasive depth, lymph node metastasis, distant metastasis, and TNM stage.
Univariate analysis indicated that pMKK4 score, tumor differentiation, and TNM
stage were correlated with disease-free survival and overall survival.
Multivariate analysis indicated that decreased pMKK4 expression was an
independent risk factor for disease-free survival in CRC patients. These results
suggest that CRC patients with low pMKK4 immunochemistry scores should be
monitored carefully for early detection of possible recurrences, especially liver
metastasis.
PMID- 28423722
TI - The importance of the genomic landscape in Waldenstrom's Macroglobulinemia for
targeted therapeutical interventions.
AB - The Literature has recently reported on the importance of genomics in the field
of hematologic malignancies, including B-cell lymphoproliferative disorders such
as Waldenstrom's Macrolgobulinemia (WM). Particularly, whole exome sequencing has
led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in
WM, occurring in about 90% and 30% of the patients, respectively. Subsequently,
functional studies have demonstrated their functional role in supporting WM
pathogenesis and disease progression, both in vitro and in vivo, thus providing
the pre-clinical evidences for extremely attractive targets for novel therapeutic
interventions in WM. Of note, recent evidences have also approached and defined
the transcriptome profiling of WM cells, revealing a signature that mirrors the
somatic aberrations demonstrated within the tumor clone. A parallel research
field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of
miRNA-155 in WM. In the present review, we focus on the latest reports on
genomics and miRNAs in WM, providing an overview of the clinical relevance of the
latest acquired knowledge about genomics and miRNA aberrations in WM.
PMID- 28423723
TI - Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects
the heart from doxorubicin-induced cardiomyopathy in mice.
AB - Doxorubicin is the chemotherapeutic drug of choice for a wide variety of cancers,
and cardiotoxicity is one of the major side effects of doxorubicin treatment. One
of the main cellular targets of doxorubicin in the heart is mitochondria.
Mitochondrial sirtuin, SIRT3 has been shown to protect against doxorubicin
induced cardiotoxicity. We have recently identified honokiol (HKL) as an
activator of SIRT3, which protects the heart from developing pressure overload
hypertrophy. Here, we show that HKL-mediated activation of SIRT3 also protects
the heart from doxorubicin-induced cardiac damage without compromising the tumor
killing potential of doxorubicin. Doxorubicin-induced cardiotoxicity is
associated with increased ROS production and consequent fragmentation of
mitochondria and cell death. HKL-mediated activation of SIRT3 prevented
Doxorubicin induced ROS production, mitochondrial damage and cell death in rat
neonatal cardiomyocytes. HKL also promoted mitochondrial fusion. We also show
that treatment with HKL blocked doxorubicin-induced cardiac toxicity in mice.
This was associated with reduced mitochondrial DNA damage and improved
mitochondrial function. Furthermore, treatments of mice, bearing prostrate tumor
xenografts, with HKL and doxorubicin showed inhibition of tumor growth with
significantly reduced cardiac toxicity. Our results suggest that HKL-mediated
activation of SIRT3 protects the heart from doxorubicin-induced cardiotoxicity
and represents a potentially novel adjunct for chemotherapy treatments.
PMID- 28423727
TI - Paclitaxel synergizes with exposure time adjusted CD22-targeting immunotoxins
against B-cell malignancies.
AB - CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or
acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL)
patients. The goal was to enhance rIT efficacy in vivo and to define a strong
combination treatment. Activity of Moxetumomab pasudotox (Moxe) and LR combined
with paclitaxel was tested against MCL cell lines in vitro and as bolus doses or
continuous infusion in xenograft models. In the KOPN-8 ALL xenograft, Moxe or
paclitaxel alone was active, but all mice died from leukemia; when combined, 60%
of the mice achieved a sustained complete remission. Against MCL cells in vitro,
LR was more active than Moxe and the cells had to be exposed to rIT for more than
24 hours for them to die. To maintain high blood levels in vivo, LR was
administered continuously by 7-day pumps achieving a well-tolerated steady plasma
concentration of 45 ng/ml. In JeKo-1 xenografts, continuously administered LR was
14-fold more active than bolus doses and the combination with paclitaxel
additionally improved responses by 135-fold. Maintaining high rIT-plasma levels
greatly improves responses in the JeKo-1 model and paclitaxel substantially
enhances bolus and continuously infused rIT, supporting a clinical evaluation
against B-cell malignancies.
PMID- 28423728
TI - MiR-590-3p suppresses epithelial-mesenchymal transition in intrahepatic
cholangiocarcinoma by inhibiting SIP1 expression.
AB - The functional roles and clinical significances of miR-590-3p in ICC remain
unclear. In the current study, we investigated the expression of miR-590-3p in
tissues and sera of ICC by real-time quantitative polymerase chain reaction. We
found miR-590-3p was significantly down-regulated in the sera and tissues of ICC
patients, especially in those patients with lymph node metastasis or distant
metastasis. AUC curves and Cox proportional hazards mode revealed serum miR-590
3p could be novel diagnostic and prognostic biomarker for ICC patients. MiR-590
3p dramatically suppressed epithelial-mesenchymal transition, cell migration, and
invasion of ICC cells. SIP1 was identified as direct and functional target of miR
590-3p in ICC cells by luciferase assays. Finally, we found SIP1 expression was
inversely correlated with miR-590-3p and closely related to diminished survival
in ICC patients. These findings reveal functional and mechanistic roles of miR
590-3p and EMT activator SIP1 in the pathogenesis of ICC.
PMID- 28423729
TI - Digitalis use and risk of gastrointestinal cancers: A nationwide population-based
cohort study.
AB - BACKGROUND: Gastrointestinal cancers are characterized by a male predominance,
suggesting a role of sex hormones. We hypothesized that digitalis medication, due
to its estrogenic properties, decreases the risk of male-predominated
gastrointestinal cancers. RESULTS: Long -term digitalis use (>=2 years) was
followed by decreased risk for several gastrointestinal cancers, but associations
were statistically significant only for liver cancer (hazard ratio [HR]=0.40, 95%
confidence interval (CI) 0.16-0.98). Short-term (<1 year) use was associated with
an increased risk of esophageal squamous cell carcinoma (HR=1.79, 95% CI 1.01
3.17), colorectal cancer (HR=1.72, 95% CI 1.57-1.89), gallbladder cancer
(HR=1.93, 95% CI 1.04-3.59), and pancreatic cancer (HR=1.33, 95% CI 1.00-1.76),
but no such increase was found among long-term users. METHODS: We performed a
nationwide population-based cohort study in Sweden. Participants included 156,385
individuals using digitalis and a reference group of 551,933 users of organic
nitrates between 2005 and 2013, who were identified in the Swedish Prescribed
Drug Register. New diagnoses of gastrointestinal cancers were identified from the
Swedish Cancer Register. Hazard ratios of gastrointestinal cancers in digitalis
users compared to users of organic nitrates were calculated from Cox proportional
hazards regression with adjustment for sex, age, municipality of residence and
comorbidity. CONCLUSIONS: This study suggests a decreased risk of male
predominated gastrointestinal cancers, particularly of liver cancer, in long-term
users of digitalis. Short-term use may be associated with an increased risk of
esophageal squamous cell carcinoma, colorectal cancer, gallbladder cancer, and
pancreatic cancer.The use of digitalis as preventive or therapeutic agents
remains to be fully evaluated.
PMID- 28423730
TI - The SCLtTAxBCR-ABL transgenic mouse model closely reflects the differential
effects of dasatinib on normal and malignant hematopoiesis in chronic phase-CML
patients.
AB - The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically
approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute
lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was
shown to impact on normal hematopoiesis and cells of the immune system.Due to the
fact that the murine in vivo studies so far have not been performed in a chronic
phase CML model under steady-state conditions, our aim was to study the
hematopoietic effects of dasatinib (20 mg/kg p.o.) in BCR-ABL expressing
SCLtTAxBCR-ABL double transgenic (dtg) mice. Dasatinib robustly antagonized the
CML phenotype in vivo in our transgenic mouse model, and this effect included
both mature and immature cell populations. However, similar to patients with CML,
the fraction of LinnegSca-1+KIT+CD48negCD150+ hematopoietic stem cells was not
reduced by dasatinib treatment, suggesting that these cells are not oncogene
addicted. Moreover, we observed differential effects of dasatinib in these
animals as compared to wild-type (wt) animals: while granulocytes were
significantly reduced in dtg animals, they were increased in wt mice. And Ter119+
erythrocytic and B220+ B cells were increased in dtg mice but decreased in wt
mice. Finally, while dasatinib induced a shift from CD49b/NK1.1 positive NK cells
from the bone marrow to the spleen in wt animals, there was no change in dtg
mice. In conclusion, the present mouse model provides a useful tool to study
mechanisms of TKI resistance and dasatinib-associated beneficial effects and
adverse events.
PMID- 28423731
TI - A multifunctional lipid nanoparticle for co-delivery of paclitaxel and curcumin
for targeted delivery and enhanced cytotoxicity in multidrug resistant breast
cancer cells.
AB - The objective of the work was to develop a multifunctional nanomedicine based on
a folate-conjugated lipid nanoparticles loaded with paclitaxel and curcumin. The
novel system combines therapeutic advantageous of efficient targeted delivery via
folate and timed-release of curcumin and paclitaxel via 2-hydroxypropyl-beta
cyclodextrin, thereby overcoming multidrug resistance in breast cancer cells (MCF
7/ADR). The faster release of curcumin from the folate-conjugated curcumin and
paclitaxel-loaded lipid nanoparticles enables sufficient p-glycoprotein
inhibition, which allows increased cellular uptake and cytotoxicity of
paclitaxel. In western blot assay, curcumin can efficiently inhibit the
expression of p-glycoprotein, conformed the enhancement of cytotoxicity by
paclitaxel. Furthermore, folate-conjugated curcumin and paclitaxel-loaded lipid
nanoparticles exhibited increased uptake of paclitaxel and curcumin into MCF
7/ADR cells through the folate receptor-mediated internalization. Taken together,
these results indicate that folate-conjugated curcumin and paclitaxel-loaded
lipid nanoparticles enables the enhanced, folate-targeted delivery of multiple
anticancer drugs by inhibiting the multi-drug resistance efficiently, which may
also serve as a useful nano-system for co-delivery of other anticancer drugs.
PMID- 28423733
TI - Nanocrystals of a new camptothecin derivative WCN-21 enhance its solubility and
efficacy.
AB - WCN-21 is a new camptothecin derivative we synthesized and has desirable anti
tumor efficacy, but its aqueous solubility is very low and hurdles the further
evaluation and development. In this study, we prepared nanocrystals of WCN-21
through a bottom-up approach to enhance its solubility and obtained WCN-21
nanorods (WND) and nanospheres (WNP). We investigated the crystallization of WND
and WNP in different temperature and solvents and found that both temperature and
solvents affect the crystal shapes and sizes. We prepared WND at 50 degrees C and
DMSO : H2O 1: 50 and WNP at 25 degrees C and DMSO : H2O 1: 100 and found they
were dispersed evenly in water with average hydrodynamic diameters 337 and 231
nm, respectively. WND and WNP increased the solubility of WCN-21 from extreme
insolubility to more than 9 and 11 mM in H2O or PBS, respectively. In vitro
studies showed that WND and WNP enhanced the uptake of WCN-21 in tumor cells by 3
and 9 folds, and increased cytotoxicity of WCN-21 in comparison with free WCN-21
by 5 and 6 folds, respectively. In xenograft tumor mice, intravenous injection of
WND and WNP enhanced the accumulation of WCN-21 in tumor tissues and improved the
anti-tumor efficacy. In addition, WND and WNP did not increase the toxicity of
WCN-21 in mice. Therefore, nanocrystal is a robust tool to improve the solubility
of insoluble drugs and holds a great potential in the application of drug
development.
PMID- 28423732
TI - Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer
metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5.
AB - Metastasis of cancer cells is a key impediment to favorable outcomes of cancer
treatment. Functional roles of long noncoding RNAs in several biological
processes, including metastasis, have recently been discovered. In our previous
work, we reported a positive correlation of increased expression of linc00673 in
NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased
proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we
demonstrate that ectopic expression of linc00673 promotes migration and invasion
of NSCLC cells. Furthermore, our results indicate that linc00673 could silence
HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter
regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC
cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the
first time identified the role of lin00673 in promoting invasion and migration of
NSCLC cells. Insights from this study may help to identify novel therapeutic
targets for NSCLC.
PMID- 28423734
TI - GATA3 and TRPS1 are distinct biomarkers and prognostic factors in breast cancer:
database mining for GATA family members in malignancies.
AB - GATA transcription factors are zinc finger DNA binding proteins that activate
transcription during development and cell differentiation. To date, 7 members of
GATA family have been reported. However, the expression patterns and the exact
roles of distinct GATA family members contributing to tumorigenesis and
progression of breast cancer (BC) remain to be elucidated. Here, we studied the
expression of GATA transcripts in a variety of tumor types compared with the
normal controls using the ONCOMINE and GOBO databases, along with their
corresponding expression profiles in an array of cancer cell lines through CCLE
analysis. Based on Kaplan-Meier plotter, we further investigated the prognostic
values of GATA members specifically high expressed in BC patients. It was found
that, when compared with normal tissues, GATA3 and TRPS1 were distinctly high
expressed in BC patients among all GATA members. GATA3 expression was
significantly associated with ESR1, while TRPS1 was correlated with ERBB2. In
survival analysis, GATA3 and TRPS1 mRNA high expressions were correlated to
better survival in BC patients, and TRPS1 high expression was significantly
associated with longer RFS in patients who have received chemotherapy. These
results suggest that GATA3 and TRPS1 are distinct biomarkers and essential
prognostic factors for breast cancer.
PMID- 28423736
TI - Laminarin promotes anti-cancer immunity by the maturation of dendritic cells.
AB - This research evaluates the effects of laminarin on the maturation of dendritic
cells and on the in vivo activation of anti-cancer immunity. In vivo treatment of
C56BL/6 mice with laminarin increased the expression levels of co-stimulatory
molecules and the production of pro-inflammatory cytokines in spleen dendritic
cells. Laminarin enhanced ovalbumin antigen presentation in spleen dendritic
cells and promoted the proliferation of OT-I and OT-II T cells. Laminarin also
induced the maturation of dendritic cells in tumor-draining lymph nodes and
protected interferon-gamma and tumor necrosis factor-alpha and proliferation of
OT-I and OT-II T cells in tumors. The combination treatment of laminarin and
ovalbumin inhibited B16-ovallbumin melanoma tumor growth and its liver metastasis
by antigen-specific immune activation, including cytotoxic T lymphocyte
activation and interferon-gamma production. Thus, these data demonstrated the
potential of laminarin as a new and useful immune stimulatory molecule for use in
cancer immunotherapy.
PMID- 28423735
TI - The long non-coding RNA NONHSAG026900 predicts prognosis as a favorable biomarker
in patients with diffuse large B-cell lymphoma.
AB - Long non-coding RNAs are known to be involved in cancer progression, but their
biological functions and prognostic values are still largely unexplored in
diffuse large B-cell lymphoma. In this study, long non-coding RNAs expression was
characterized in 1,403 samples including normal and diffuse large B-cell lymphoma
by repurposing 7 microarray datasets. Compared with any stage of normal B cells,
NONHSAG026900 expression was significantly decreased in tumor samples. And in
germinal center B-cell subtype, the significantly higher expression of
NONHSAG026900 indicated it was a favorable prognosis biomarker. Then the
prognostic power of NONHSAG026900 was validated with another independent dataset
and NONHSAG026900 improved the predictive power of International Prognostic Index
as an independent factor. Moreover, functional prediction and validation
demonstrated that NONHSAG026900 could inhibit cell cycle activity to restrain
tumor proliferation. These findings identified NONHSAG026900 as a novel
prognostic biomarker and offered a new therapeutic target for diffuse large B
cell lymphoma patients.
PMID- 28423737
TI - RMP promotes epithelial-mesenchymal transition through NF-kappaB/CSN2/Snail
pathway in hepatocellular carcinoma.
AB - Epithelial-mesenchymal transition (EMT) is a significant risk factor for
metastasis in hepatocellular carcinoma (HCC) patients and with poor prognosis. In
this study, we demonstrate the key role of RPB5-mediating protein (RMP) in EMT of
HCC cells and the mechanism by which RMP promote EMT. RMP increases migration,
invasion, and the progress of EMT of HCC cells, which facilitates the
accumulation of Snail, a transcriptional repressor involved in EMT initiation. NF
kappaB is activated by RMP, which directly promotes the expression of COP9
signalosome 2 (CSN2) to repress the degradation of Snail. Pulmonary metastases
mouse model demonstrates that RMP induces metastasis in vivo. Immunohistochemical
analysis of human HCC tissues confirms the correlation of RMP with the expression
of E-cadherin, p65, CSN2 and Snail in vivo. Collectively, these findings indicate
that RMP promotes EMT and HCC metastasis through NF-kappaB/CSN2/Snail pathway.
These results suggest that RMP and p65 may serve as potential candidates of the
targets in the treatment of metastatic HCC.
PMID- 28423738
TI - LncRNA Snhg1, a non-degradable sponge for miR-338, promotes expression of proto
oncogene CST3 in primary esophageal cancer cells.
AB - Competing endogenous RNA (ceRNA) is a newly proposed mechanism that describes a
crosstalk among lncRNAs, mRNAs and their shared miRNAs. In this study, the role
of miR-338-3p (miR-338) in the progression of esophageal cancer and its involve
in the ceRNA regulatory circuit lncRNA-Snhg1/CST3 were explored. MiR-338
displayed a 30% decreased expression in esophageal squamous cell carcinoma
tissues compared with the adjacent. Then, proto-oncogene CST3 was predicted and
validated as a target gene of miR-338. Gain-and-loss-function experiments
indicated that miR-338 suppressed expression of CST3 protein (also Cystatin C,
CysC), promoted expression of apoptotic proteins caspase-8/3, attenuated
esophageal carcinoma cell growth and induced its apoptosis. In addition, lncRNA
Snhg1 was significantly upregulated in esophageal carcinoma tissues and promoted
esophageal carcinoma cell growth. Furthermore, our results from bioinformatics,
luciferase reporter gene and RNA pull-down assays indicated that Snhg1 could be
directly bound by miR-338. Snhg1 acted as a non-degradable sponge to relieve the
suppression on CST3 caused by miR-338. In conclusion, lncRNA-Snhg1 promoted cell
proliferation by acting as a non-degradable sponge for the tumor suppressor miR
338 in esophageal cancer cells.
PMID- 28423740
TI - Prognosis of surgery combined with different adjuvant therapies in esophageal
cancer treatment: a network meta-analysis.
AB - : This network meta-analysis was conducted to assess whether the efficacy of
surgery with adjuvant therapies, including radiotherapy (RT+S), chemotherapy
(CT+S), and chemoradiotherapy (CRT+S) have better performance in esophageal
cancer treatment and management. PubMed and EMBASE were used to search for
relevant trials. Both conventional pair-wise and network meta-analyses were
carried out. The surface under the cumulative ranking curve (SUCRA) was used to
rank interventions based on the efficacy of the treatment method. As for 3-year
overall survival (OS), CRT+S showed the highest efficacy (CRT+S vs. SURGERY:
HR=0.81, 95% CrI =0.73-0.90; CRT+S vs. CT+S: HR=0.82, 95% CrI =0.70-0.95; CRT+S
vs. RT+S: HR=0.77, 95% CrI =0.62-0.95). For disease-free survival, CRT+S showed
efficacy over CT+S ((HR =0.70, 95% CrI =0. 59-0.83). In conclusion, CRT+S showed
a better performance for survival outcomes and ranks best among all therapies.
The results of our study can provide guidance for medical decisions and treatment
options that may help clinical practitioners improve the efficacy of EC
treatment.
PMID- 28423741
TI - Lenalidomide and the risk of serious infection in patients with multiple myeloma:
a systematic review and meta-analysis.
AB - The immunomodulatory drug lenalidomide is highly effective against newly
diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even
fatal infections have been associated with its use. In this meta-analysis, we
assessed the overall risk of infection to MM patients treated with lenalidomide.
Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected
from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial
Registration website, and from meeting abstracts and virtual presentations at the
American Society of Clinical Oncology. Main outcome measures were overall
incidence, relative risk (RR), and 95% confidence intervals (CIs) of reported
infection events. Fixed-effect or random-effect models were used in the
statistical analyses, depending on the between-study heterogeneity. The overall
incidence of high-grade infection was 14.32% (95% CI: 12.08%-16.90%) and high
grade infection's pooled RR was 2.23 (95% CI: 1.71-2.91, P < 0.0001) for all 11
studies evaluated. No evidence of publication bias for the incidence of high
grade infection was detected using Begg's funnel plot and Egger's test (P = 0.2;
95% CI: -1.70, 1.23). From this meta-analysis, it appears lenalidomide use is
associated with an increased risk of high-grade infection. Moreover, fatal
infection events occurred only in patients treated with lenalidomide; no
infection-related deaths were observed among controls. These data indicate that
accurate diagnosis and optimal management of infection in MM patients treated
with lenalidomide could be critical for treatment efficacy.
PMID- 28423743
TI - 1. Connected and Digital Health.
PMID- 28423744
TI - Design and Validation of a Platform to Evaluate mHealth Apps.
AB - Emerging technologies show great potential in the field of patient care. One such
technology is mobile heath applications (mhealth apps), which have exploded in
number and variety in recent years, and offer great promise in the ability to
collect and monitor patient health data. Despite their apparent success in
proliferation and user adoption, these applications struggle to integrate into
the primary care system and there is scant information regarding their efficacy
to effect patient behavior and consequently health outcomes. In this paper we
investigate the potential of a promising clinical evaluation methodology,
response adaptive randomized clinical trials, to rapidly and effectively evaluate
the efficacy and effectiveness of mhealth apps and to personalize mhealth app
selection to individualize patient benefit. Diabetes prevention provides the use
case for evaluating the case for and against response-adaptive randomized trials.
PMID- 28423745
TI - Reasoning and Data Representation in a Health and Lifestyle Support System.
AB - Case-based reasoning and data interpretation is an artificial intelligence
approach that capitalizes on past experience to solve current problems and this
can be used as a method for practical intelligent systems. Case-based data
reasoning is able to provide decision support for experts and clinicians in
health systems as well as lifestyle systems. In this project we were focusing on
developing a solution for healthy ageing considering daily activities, nutrition
as well as cognitive activities. The data analysis of the reasoner followed state
of the art guidelines from clinical practice. Guidelines provide a general
framework to guide clinicians, and require consequent background knowledge to
become operational, which is precisely the kind of information recorded in
practice cases; cases complement guidelines very well and helps to interpret
them. It is expected that the interest in case-based reasoning systems in the
health.
PMID- 28423742
TI - Novel potential predictive markers of sunitinib outcomes in long-term responders
versus primary refractory patients with metastatic clear-cell renal cell
carcinoma.
AB - BACKGROUND: Several potential predictive markers of efficacy of targeted agents
in patients with metastatic renal cell carcinoma (mRCC) have been identified.
Interindividual heterogeneity warrants further investigation. PATIENTS AND
METHODS: Multicenter, observational, retrospective study in patients with clear
cell mRCC treated with sunitinib. Patients were classified in two groups: long
term responders (LR) (progression-free survival (PFS)>=22 months and at least
stable disease), and primary refractory (PR) (progressive disease within 3-months
of sunitinib onset). Objectives were to compare baseline clinical factors in both
populations and to correlate tumor expression of selected signaling pathways
components with sunitinib PFS. RESULTS: 123 patients were analyzed (97 LR, 26
PR). In the LR cohort, overall response rate was 79% and median duration of best
response was 30 months. Median PFS and overall survival were 43.2 (95% confidence
intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At
baseline PR patients had a significantly lower proportion of nephrectomies,
higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time
to and higher presence of metastases, and increased Fuhrman grade. Higher levels
of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated
populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of
hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged
survival. No statistical significant associations between hsa-miR-23b or hsa-miR
27b and the expression of c-Met were found. CONCLUSIONS: Certain mRCC patients
treated with sunitinib achieve extremely long-term responses. Favorable baseline
hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa
miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers
of sunitinib response.
PMID- 28423746
TI - Feasibility of Representing a Danish Microbiology Model Using FHIR.
AB - Achieving interoperability in health is a challenge and requires standardization.
The newly developed HL7 standard: Fast Healthcare Interoperability Resources
(FHIR) promises both flexibility and interoperability. This study investigates
the feasibility of expressing a Danish microbiology message model content in FHIR
to explore whether complex in-use legacy models can be migrated and what
challenges this may pose. The Danish microbiology message model (the DMM) is used
as a case to illustrate challenges and opportunities accosted with applying the
FHIR standard. Mapping of content from DMM to FHIR was done as close as possible
to the DMM to minimize migration costs except when the structure of the content
did not fit into FHIR. From the DMM a total of 183 elements were mapped to FHIR.
75 (40.9%) elements were modeled as existing FHIR elements and 96 (52.5%)
elements were modeled as extensions and 12 (6.6%) elements were deemed
unnecessary because of build-in FHIR characteristics. In this study, it was
possible to represent the content of a Danish message model using HL7 FHIR.
PMID- 28423747
TI - Establishment of Requirements and Methodology for the Development and
Implementation of GreyMatters, a Memory Clinic Information System.
AB - INTRODUCTION: The aim of the paper is to establish the requirements and
methodology for the development process of GreyMatters, a memory clinic system,
outlining the conceptual, practical, technical and ethical challenges, and the
experiences of capturing clinical and research oriented data along with the
implementation of the system. METHODS: The methodology for development of the
information system involved phases of requirements gathering, modeling and
prototype creation, and 'bench testing' the prototype with experts. The standard
Institute of Electrical and Electronics Engineers (IEEE) recommended approach for
the specifications of software requirements was adopted. An electronic health
record (EHR) standard, EN13606 was used, and clinical modelling was done through
archetypes and the project complied with data protection and privacy legislation.
RESULTS: The requirements for GreyMatters were established. Though the initial
development was complex, the requirements, methodology and standards adopted made
the construction, deployment, adoption and population of a memory clinic and
research database feasible. The electronic patient data including the assessment
scales provides a rich source of objective data for audits and research and to
establish study feasibility and identify potential participants for the clinical
trials. CONCLUSION: The establishment of requirements and methodology, addressing
issues of data security and confidentiality, future data compatibility and
interoperability and medico-legal aspects such as access controls and audit
trails, led to a robust and useful system. The evaluation supports that the
system is an acceptable tool for clinical, administrative, and research use and
forms a useful part of the wider information architecture.
PMID- 28423748
TI - Nurses' Perspectives on In-Home Monitoring of Elderlies's Motion Pattern.
AB - In-home monitoring systems have been proposed to support aging in place and
facilitate home care service. Through a qualitative approach the study explores
nurses' existing challenges and perspectives of an in-home monitoring system.
Results indicate that nurses base care decisions on multiple, and sometimes,
unreliable information sources. However, access to information about elderlies'
physical motion could support the care planning process by reducing ambiguity and
raising attention. Hence, a simple and affordable system that largely relies on
nurses to interpret the sensed data could bring additional value.
PMID- 28423749
TI - Monitoring Activities Related to Medication Adherence in Ambient Assisted Living
Environments.
AB - A recent trend in healthcare is to motivate patients to self-manage their health
conditions in home-based settings. Medication adherence is an important aspect in
disease self-management since sub-optimal medication adherence by the patient can
lead to serious healthcare costs and discomfort for the patient. In order to
alleviate the limitations of self-reported medication adherence, we can use
ambient assistive living (AAL) technologies in smart environments. Activity
recognition services allow to retrieve self-management information related to
medication adherence in a less intrusive way. By remotely monitor compliance with
medication adherence, self-management program's interventions can be tailored and
adapted based on the observed patient's behaviour. To address this challenge, we
present an AAL framework that monitor activities related to medication adherence.
PMID- 28423750
TI - Design, Implementation and Operation of a Reading Center Platform for Clinical
Studies.
AB - Clinical reading centers provide expertise for consistent, centralized analysis
of medical data gathered in a distributed context. Accordingly, appropriate
software solutions are required for the involved communication and data
management processes. In this work, an analysis of general requirements and
essential architectural and software design considerations for reading center
information systems is provided. The identified patterns have been applied to the
implementation of the reading center platform which is currently operated at the
Center of Ophthalmology of the University Hospital of Tubingen.
PMID- 28423751
TI - Web Validation Service for Ensuring Adherence to the DICOM Standard.
AB - The DICOM Standard has been fundamental for ensuring the interoperability of
Picture Archive and Communications Systems (PACS). By compiling rigorously to the
standard, medical imaging equipment and applications from different vendors can
share their data, and create integrated workflows which contributes to better
quality healthcare services. However, DICOM is a complex, flexible and very
extensive standard. Thus, it is difficult to attest the conformity of data
structures produced by DICOM applications resulting in unexpected behaviors,
errors and malfunctions. Those situations may be critical for regular PACS
operation, resulting in serious losses to the healthcare enterprise. Therefore,
it is of paramount importance that application vendors and PACS administrators
are confident that their applications follow the standard correctly. In this
regard, we propose a method for validating the compliance of PACS application
with the DICOM Standard. It can capture the intricate dependency structure of
DICOM modules and data elements using a relatively simple description language.
The modular nature of our method allows describing each DICOM module, their
attributes, and dependencies on a re-usable basis. As a result, our validator is
able to encompass the numerous modules present in DICOM, as well as keep up with
the emergence of new ones.
PMID- 28423752
TI - A Decision Support System for Cardiac Disease Diagnosis Based on Machine Learning
Methods.
AB - This paper proposes a decision support system for screening pediatric cardiac
disease in primary healthcare centres relying on the heart sound time series
analysis. The proposed system employs our processing method which is based on the
hidden Markov model for extracting appropriate information from the time series.
The binary output resulting from the method is discriminative for the two classes
of time series existing in our databank, corresponding to the children with heart
disease and the healthy ones. A total 90 children referrals to a university
hospital, constituting of 55 healthy and 35 children with congenital heart
disease, were enrolled into the study after obtaining the informed consent.
Accuracy and sensitivity of the method was estimated to be 86.4% and 85.6%,
respectively, showing a superior performance than what a paediatric cardiologist
could achieve performing auscultation. The method can be easily implemented using
mobile and web technology to develop an easy-to-use tool for paediatric cardiac
disease diagnosis.
PMID- 28423753
TI - Severity Summarization and Just in Time Alert Computation in mHealth Monitoring.
AB - Mobile health is fast evolving into a practical solution to remotely monitor high
risk patients and deliver timely intervention in case of emergencies. Building
upon our previous work on a fast and power efficient summarization framework for
remote health monitoring applications, called RASPRO (Rapid Alerts Summarization
for Effective Prognosis), we have developed a real-time criticality detection
technique, which ensures meeting physician defined interventional time. We also
present the results from initial testing of this technique.
PMID- 28423754
TI - Towards Safe and Efficient Child Primary Care - Gaps in the Use of Unique
Identifiers in Europe.
AB - In order to provide for best possible child health care, timely access to all
relevant medical data is of vital importance. The aim of this study is to
investigate the use of unique identifiers, a key instrument in this regard, in
the countries of Europe. A survey was carried out in all 28 European Member
States plus 2 European Economic Area countries in 2015, and refreshed in 2016. In
23 countries unique identifiers are used to link children's health records. Five
countries indicated they currently do not link child health records, and two have
no such plans. There is variety as regards the type of number and the issuing
process.
PMID- 28423755
TI - Why Are Children's Interests Invisible in European National E-Health Strategies?
AB - Harnessing the power of IT solutions in child primary care requires strategic
thought at national level, and good health care delivery needs this support. The
aim of this study was to investigate whether children's needs are considered in
national e-health strategies in Europe. In 2016, a survey was carried out in all
28 European Member States plus 2 European Economic Area countries. Sixteen
countries fail to mention children's needs at all. Only eleven of 27 countries
mention children and adolescents in their national e-health strategy documents
ranging from mere data protection concerns to comprehensive IT approaches for the
improvement of child primary care.
PMID- 28423756
TI - Shared Decision Making via Personal Health Record Technology for Routine Use of
Diabetic Youth: A Study Protocol.
AB - Engaging patients in the self-management decision-making provides opportunities
for positive health outcomes. The process of shared decision making (SDM) is
touted as the pinnacle of patient-centred care, yet it has been difficult to
implement in practice. Access to tools resulting from the integration of all
health data and clinical evidence, and an ease of communications with care
providers are needed to engage patients in decision making. Personal health
record (PHR) technology is a promising approach for overcoming such barriers. Yet
there is a scarcity of studies on system design for SDM via PHR. This paper
describes a study protocol to identify functional requirements of PHR for
facilitating SDM and factors that would influence the embedding of the proposed
system in clinical practice.
PMID- 28423757
TI - A Medication Reminder Mobile App: Does It Work for Different Age Ranges.
AB - Successful medication adherence particularly in elderly with chronic diseases
will improve their self-management. Medication reminder systems could be useful
to improve this adherence. This study consists of two phases, designing a mobile
medical app based on Android platform and then its evaluation. To develop this
application, first, the use case scenarios have been hypothesized in partnership
with health professionals and patients used to take medications daily. Unified
Modeling Language was used to model the use cases. The evaluation was performed
with usability testing and efficacy testing. The results show that the app was
well accepted both in young people and older adults. Engaging target users and
health professionals in the conception and development of a health-related app
could have better results in the usability and the efficacy of the app.
PMID- 28423758
TI - Internet of Things in Health Trends Through Bibliometrics and Text Mining.
AB - Recently a new buzzword has slowly but surely emerged, namely the Internet of
Things (IoT). The importance of IoT is identified worldwide both by organisations
and governments and the scientific community with an incremental number of
publications during the last few years. IoT in Health is one of the main pillars
of this evolution, but limited research has been performed on future visions and
trends. Thus, in this study we investigate the longitudinal trends of Internet of
Things in Health through bibliometrics and use of text mining. Seven hundred
seventy eight (778) articles were retrieved form The Web of Science database from
1998 to 2016. The publications are grouped into thirty (30) clusters based on
abstract text analysis resulting into some eight (8) trends of IoT in Health.
Research in this field is obviously obtaining a worldwide character with specific
trends, which are worth delineating to be in favour of some areas.
PMID- 28423759
TI - Developing the Safety Case for MediPi: An Open-Source Platform for Self
Management.
AB - mHealth and Telehealth technologies are increasingly used to provide
personalised, interactive and timely access to health data, thereby helping
patients take a more active role in their care process. However, similar to any
intervention, the use of these technologies has to be assured to justify that
they do not compromise patient safety. In this paper, we discuss the development
of a safety case for MediPi; a research prototype for a low-cost open-source
digital platform that collects physiological data from patients, at home, and
makes it available to decision-support systems used by clinicians. We identify
potential hazardous failures associated with the use of MediPi and examine
current risk controls. We also explore the modular structure of the overall
safety case of the platform. We conclude with a discussion of patient safety
challenges related to the unsupervised nature of the care setting and the use of
commercial off-the-shelf personal devices.
PMID- 28423760
TI - UK Health and Social Care Case Studies: Iterative Technology Development.
AB - As a result of increasing demand in the face of reducing resources, technology
has been implemented in many social and health care services to improve service
efficiency. This paper outlines the experiences of deploying a 'Software as a
Service' application in the UK social and health care sectors. The case studies
demonstrate that every implementation is different, and unique to each
organisation. Technology design and integration can be facilitated by ongoing
engagement and collaboration with all stakeholders, flexible design, and
attention to interoperability to suit services and their workflows.
PMID- 28423762
TI - Predicting the Pathogenic Impact of Sequence Variation in the Human Genome.
AB - Sequencing data will become widely available in clinical practice within the near
future. Uptake of sequence data is currently being stimulated within the UK
through the government-funded 100,000 genomes project (Genomics England), with
many similar initiatives being planned and supported internationally. The
analysis of the large volumes of data derived from sequencing programmes poses a
major challenge for data analysis. In this paper we outline progress we have made
in the development of predictors for estimating the pathogenic impact of single
nucleotide variants, indels and haploinsufficiency in the human genome. The
accuracy of these methods is enhanced through the development of disease-specific
predictors, trained on appropriate data, and used within a specific disease
context. We outline current research on the development of disease-specific
predictors, specifically in the context of cancer research.
PMID- 28423763
TI - Learning Healthcare System for the Prescription of Genetic Testing in the
Gynecological Cancer Risk.
AB - Clinical evidence demonstrates that BRCA 1 and BRCA2 mutations can develop a
gynecological cancer but genetic testing has a high cost to the healthcare
system. Besides, several studies in the literature indicate that performing these
genetic tests to the population is not cost-efficient. Currently, our physicians
do not have a system to provide them the support for prescribing genetic tests. A
Decision Support System for prescribing these genetic tests in BRCA1 and BRCA2
and preventing gynecological cancer risks has been designed, developed and
deployed in the Virgen del Rocio University Hospital (VRUH). The technological
architecture integrates a set of open source tools like Mirth Connect,
OpenClinica, OpenCDS, and tranSMART in addition to several interoperability
standards. The system allows general practitioners and gynecologists to classify
patients as low risk (they do not require a specific treatment) or high risk
(they should be attended by the Genetic Council). On the other hand, by means of
this system we are also able to standardize criteria among professionals to
prescribe these genetic tests. Finally, this system will also contribute to
improve the assistance for this kind of patients.
PMID- 28423764
TI - An Automatic Approach for Analyzing Treatment Effectiveness Based on Medication
Hierarchy - The Myocardial Infarction Case Study.
AB - Treatment effectiveness plays a fundamental role in patient therapies. In most
observational studies, researchers often design an analysis pipeline for a
specific treatment based on the study cohort. To evaluate other treatments in the
data set, much repeated and multifarious work including cohort construction,
statistical analysis need to be done. In addition, as treatments are often with
an intrinsic hierarchical relationship, many rational comparable treatment pairs
can be derived as new treatment variables besides the original single treatment
one from the original cohort data set. In this paper, we propose an automatic
treatment effectiveness analysis approach to solve this problem. With our
approach, clinicians can assess the effect of treatments not only more
conveniently but also more thoroughly and comprehensively. We applied this method
to a real world case of estimating the drug effectiveness on Chinese Acute
Myocardial Infarction (CAMI) data set and some meaningful results are obtained
for potential improvement of patient treatments.
PMID- 28423765
TI - Evaluation of Machine Learning Methods to Predict Coronary Artery Disease Using
Metabolomic Data.
AB - Metabolomic data can potentially enable accurate, non-invasive and low-cost
prediction of coronary artery disease. Regression-based analytical approaches
however might fail to fully account for interactions between metabolites, rely on
a priori selected input features and thus might suffer from poorer accuracy.
Supervised machine learning methods can potentially be used in order to fully
exploit the dimensionality and richness of the data. In this paper, we
systematically implement and evaluate a set of supervised learning methods (L1
regression, random forest classifier) and compare them to traditional regression
based approaches for disease prediction using metabolomic data.
PMID- 28423766
TI - Dermatology Disease Prediction Based on Two Step Cascade Genetic Algorithm
Optimization of ANFIS Parameters.
AB - The aim of this study is to present novel algorithms for prediction of
dermatological disease using only dermatological clinical features and diagnoses
collected in real conditions. A combination of the Adaptive Neuro-Fuzzy Inference
Systems (ANFIS) and Genetic algorithm (GA) for ANFIS subtractive clustering
parameter optimization has been suggested for the first level of fuzzy model
optimization. After that, a genetic optimized ANFIS fuzzy structure is used as
input in GA for the second level of fuzzy model optimization. We used double 2
fold Cross validation for generating different validation sets for model
improvements. Our approach is performed in the MATLAB environment. We compared
results with the other studies. The results confirm that the proposed model
achieves accuracy rates which are higher than the one with the previous model.
PMID- 28423767
TI - Querying EHRs with a Semantic and Entity-Oriented Query Language.
AB - While the digitization of medical documents has greatly expanded during the past
decade, health information retrieval has become a great challenge to address many
issues in medical research. Information retrieval in electronic health records
(EHR) should also reduce the difficult tasks of manual information retrieval from
records in paper format or computer. The aim of this article was to present the
features of a semantic search engine implemented in EHRs. A flexible, scalable
and entity-oriented query language tool is proposed. The program is designed to
retrieve and visualize data which can support any Conceptual Data Model. The
search engine deals with structured and unstructured data, for a sole patient
from a caregiver perspective, and for a number of patients (e.g. epidemiology).
Several types of queries on a test database containing 2,000 anonymized patients
EHRs (i.e. approximately 200,000 records) were tested. These queries were able to
accurately treat symbolic, textual, numerical and chronological data.
PMID- 28423768
TI - Evaluation of the Terminology Coverage in the French Corpus LiSSa.
AB - Extracting concepts from medical texts is a key to support many advanced
applications in medical information retrieval. Entity recognition in French texts
is moreover challenged by the availability of many resources originally developed
for English texts. This paper proposes an evaluation of the terminology coverage
in a corpus of 50,000 French articles extracted from the bibliographic database
LiSSa. This corpus was automatically indexed with 32 health terminologies,
published in French or translated. Then, the terminologies providing the best
coverage of these documents were determined. The results show that major
resources such as the NCI and SNOMED CT thesauri achieve the largest annotation
of the corpus while specific French resources prove to be valuable assets.
PMID- 28423769
TI - Linked Data Applications Through Ontology Based Data Access in Clinical Research.
AB - Clinical care and research data are widely dispersed in isolated systems based on
heterogeneous data models. Biomedicine predominantly makes use of connected
datasets based on the Semantic Web paradigm. Initiatives like Bio2RDF created
Resource Description Framework (RDF) versions of Omics resources, enabling
sophisticated Linked Data applications. In contrast, electronic healthcare
records (EHR) data are generated and processed in diverse clinical subsystems
within hospital information systems (HIS). Usually, each of them utilizes a
relational database system with a different proprietary schema. Semantic
integration and access to the data is hardly possible. This paper describes ways
of using Ontology Based Data Access (OBDA) for bridging the semantic gap between
existing raw data and user-oriented views supported by ontology-based queries.
Based on mappings between entities of data schemas and ontologies data can be
made available as materialized or virtualized RDF triples ready for querying and
processing. Our experiments based on CentraXX for biobank and study management
demonstrate the advantages of abstracting away from low level details and
semantic mediation. Furthermore, it becomes clear that using a professional
platform for Linked Data applications is recommended due to the inherent
complexity, the inconvenience to confront end users with SPARQL, and scalability
and performance issues.
PMID- 28423770
TI - Epidemiological Models Lacking Process Noise Can Be Overconfident.
AB - Mathematic models of epidemics are the key tool for predicting future course of
disease in a population and analyzing the effects of possible intervention
policies. Typically, models that produce deterministic are applied for making
predictions and reaching decisions. Stochastic modeling methods present an
alternative. Here, we demonstrate by example why it is important that stochastic
modeling be used in population health decision support systems.
PMID- 28423771
TI - Disentangling Prognostic and Predictive Biomarkers Through Mutual Information.
AB - We study information theoretic methods for ranking biomarkers. In clinical
trials, there are two, closely related, types of biomarkers: predictive and
prognostic, and disentangling them is a key challenge. Our first step is to
phrase biomarker ranking in terms of optimizing an information theoretic
quantity. This formalization of the problem will enable us to derive rankings of
predictive/prognostic biomarkers, by estimating different, high dimensional,
conditional mutual information terms. To estimate these terms, we suggest
efficient low dimensional approximations. Finally, we introduce a new
visualisation tool that captures the prognostic and the predictive strength of a
set of biomarkers. We believe this representation will prove to be a powerful
tool in biomarker discovery.
PMID- 28423772
TI - IntegrIT - Towards Utilizing the Swedish National Health Information Exchange
Platform for Clinical Research.
AB - This paper describes how the Swedish national Health Information Exchange
platform can be used to facilitate clinical research in the future. Different e
services for different user groups are being developed using a user-centered
design approach. The main user groups are study participants, clinical
researchers and healthcare professionals. The different e-services are based on
an in-depth analysis of the clinical research process, and the main identified
needs relate to recruitment of study participants, access to clinical data from
different sources as well as improved tools for patients' self-reporting. The
national Swedish HIE platform has the potential to enable a seamless connection
between patients/citizens as study participants, health care professionals and
everyday clinical work and clinical researchers in both academia and industry.
PMID- 28423773
TI - Introducing a Method for Transformation of Paper-Based Research Data into Concept
Based Representation with openEHR.
AB - Combining research data and clinical routine data is a chance for medical
research. We present our method for the transformation of paper-based research
data into a concept-based representation. With this representation the study data
from research projects can be combined with data from clinical tools with less
integration effort. We applied and verified our method using data from a current
research study. In this paper we also show our main challenges and lessons
learned. Clinical assessment data and study diaries from a long term study (n=24,
3 months observation time each, 17 different clinical assessments) stored on
paper were used as the data set. An openEHR-based electronical health record
platform was adapted for acquisition and representation of the research data. To
avoid transcription errors, the data was entered twice by different student
assistants. A third compared and corrected both data sets. Content models (17
archetypes and five templates from openEHR concept) based on clinical assessments
were created manually. Web forms for data entry were created automatically on the
basis of this concept-based content models. Additionally, form functionalities to
support data entry and comparison were implemented. In total, 829 compositions
were entered by the student assistants. With our developed method, we are able to
represent the study data in a clinical concept-based platform, which means less
integration effort for access and processing of research and clinical data. Some
minor difficulties occurred during the process. All in all, adapting routine
tools, like the EHR platform, seems to be convenient to deal with research data.
PMID- 28423774
TI - The 'PEARL' Data Warehouse: Initial Challenges Faced with Semantic and Syntactic
Interoperability.
AB - Data about patients are available from diverse sources, including those routinely
collected as individuals interact with service providers, and those provided
directly by individuals through surveys. Linking these data can lead to a more
complete picture about the individual, to inform either care decision making or
research investigations. However, post-linkage, differences in data recording
systems and formats present barriers to achieving these aims. This paper
describes an approach to combine linked GP records with study observations, and
reports initial challenges related to semantic and syntactic interoperability
issues.
PMID- 28423775
TI - Combining Different Privacy-Preserving Record Linkage Methods for Hospital
Admission Data.
AB - Record linkage (RL) is the process of identifying pairs of records that
correspond to the same entity, for example the same patient. The basic approach
assigns to each pair of records a similarity weight, and then determines a
certain threshold, above which the two records are considered to be a match.
Three different RL methods were applied under privacy-preserving conditions on
hospital admission data: deterministic RL (DRL), probabilistic RL (PRL), and
Bloom filters. The patient characteristics like names were one-way encrypted
(DRL, PRL) or transformed to a cryptographic longterm key (Bloom filters). Based
on one year of hospital admissions, the data set was split randomly in 30
thousand new and 1,5 million known patients. With the combination of the three RL
methods, a positive predictive value of 83 % (95 %-confidence interval 65 %-94 %)
was attained. Thus, the application of the presented combination of RL-methods
seem to be suited for other applications of population-based research.
PMID- 28423776
TI - Application of Correspondence Analysis to Graphically Investigate Associations
Between Foods and Eating Locations.
AB - This paper presents the application of correspondence analysis (CA) for
investigating associations using confidence regions (CRs) with a focus on
facilitating mining the data and hypothesis generation. We study the relationship
between locations and "less-healthy" food consumption by UK teenagers. CA allows
for a quick visual inspection of the various association structures that exist
between the categories of cross-classified variables in large datasets derived
with varying study designs. The hypotheses generated by the visual display can
then be independently tested using suitable regression models. CA makes use of
readily available software tools and of robust statistical tests amenable to
interpretation.
PMID- 28423777
TI - Data Driven Quality Improvement of Health Professions Education: Design and
Development of CLUE - An Interactive Curriculum Data Visualization Tool.
AB - Curriculum Mapping and dynamic visualization is quickly becoming an integral
aspect of quality improvement in support of innovations which drive curriculum
quality assurance processes in medical education. CLUE (Curriculum Explorer) a
highly interactive, engaging and independent platform was developed to support
curriculum transparency, enhance student engagement, and enable granular search
and display. Reflecting a design based approach to meet the needs of the school's
varied stakeholders, CLUE employs an iterative and reflective approach to drive
the evolution of its platform, as it seeks to accommodate the ever-changing needs
of our stakeholders in the fast pace world of medicine and medical education
today. CLUE exists independent of institutional systems and in this way, is
uniquely positioned to deliver a data driven quality improvement resource, easily
adaptable for use by any member of our health care professions.
PMID- 28423778
TI - Developing Healthcare Data Analytics APPs with Open Data Science Tools.
AB - Recent advances in big data analytics provide more flexible, efficient, and open
tools for researchers to gain insight from healthcare data. Whilst many tools
require researchers to develop programs with programming languages like Python, R
and so on, which is not a skill set grasped by many researchers in the healthcare
data analytics area. To make data science more approachable, we explored existing
tools and developed a practice that can help data scientists convert existing
analytics pipelines to user-friendly analytics APPs with rich interactions and
features of real-time analysis. With this practice, data scientists can develop
customized analytics pipelines as APPs in Jupyter Notebook and disseminate them
to other researchers easily, and researchers can benefit from the shared notebook
to perform analysis tasks or reproduce research results much more easily.
PMID- 28423779
TI - Fast and Efficient Feature Engineering for Multi-Cohort Analysis of EHR Data.
AB - We present a framework for feature engineering, tailored for longitudinal
structured data, such as electronic health records (EHRs). To fast-track feature
engineering and extraction, the framework combines general-use plug-in
extractors, a multi-cohort management mechanism, and modular memoization. Using
this framework, we rapidly extracted thousands of features from diverse and large
healthcare data sources in multiple projects.
PMID- 28423780
TI - Development and Evaluation of a Case-Based Retrieval Service.
AB - Identifying similar patients might greatly facilitate the treatment of a given
patient, enabling to observe the response and outcome to a particular treatment.
Case-based retrieval services dealing with natural language processing are of
major importance to deal with the significant amount of unstructured clinical
data. In this paper, we present the development and evaluation of a case-based
retrieval (CBR) service tested on a collection of Italian pediatric cardiology
cases. Cases are indexed and a search engine is proposed. Search functionalities,
such as interactive MeSH normalization and relevance feedback, are proposed.
While the qualitative evaluation aims to provide feedback and recommendations,
the quantitative evaluation enables to estimate the precision of the system. In
more than half of the cases and for up to two thirds of them, the system is able
to suggest a similar episode of care at first rank. With an improvement of the
feedback relevance strategy, we can expect an improvement of the precision. The
CBR can be expanded to multilingual EHR and other fields.
PMID- 28423781
TI - Learning Differentially Expressed Gene Pairs in Microarray Data.
AB - To identify differentially expressed genes (DEGs) in analysis of microarray data,
a majority of existing filter methods rank gene individually. Such a paradigm
could overlook the genes with trivial individual discriminant powers but
significant powers of discrimination in their combinations. This paper proposed
an impurity metric in which the number of split intervals for each feature is
considered as a parameter to be optimized for gaining maximal discrimination. The
proposed method was first evaluated by applying to a synthesized noisy
rectangular grid dataset, in which the significant feature pair which forms a
rectangular grid pattern was successfully recognized. Furthermore, applying to
the identification of DEGs on colon microarray data, the proposed method
demonstrated that it could become an alternative to Fisher's test for the
prescreening of genes which led to better performance of the SVM-RFE method.
PMID- 28423782
TI - Developing a Manually Annotated Corpus of Clinical Letters for Breast Cancer
Patients on Routine Follow-Up.
AB - This paper introduces the annotation schema and annotation process for a corpus
of clinical letters describing the disease course and treatment of oestrogen
receptor positive breast cancer patients, after completion of primary surgery and
radiotherapy treatment. Concepts related to therapy, clinical signs, and
recurrence, as well as relationships linking these, are identified and annotated
in 200 letters. This corpus will provide the basis for development of natural
language processing tools for automatic extraction of key clinical factors from
such letters.
PMID- 28423783
TI - Automated Diagnosis Coding with Combined Text Representations.
AB - Automated diagnosis coding can be provided efficiently by learning predictive
models from historical data; however, discriminating between thousands of codes
while allowing a variable number of codes to be assigned is extremely difficult.
Here, we explore various text representations and classification models for
assigning ICD-9 codes to discharge summaries in MIMIC-III. It is shown that the
relative effectiveness of the investigated representations depends on the
frequency of the diagnosis code under consideration and that the best performance
is obtained by combining models built using different representations.
PMID- 28423784
TI - Using Statistics and Data Mining Approaches to Analyze Male Sexual Behaviors and
Use of Erectile Dysfunction Drugs Based on Large Questionnaire Data.
AB - The prevalence of erectile dysfunction (ED) has been extensively studied
worldwide. Erectile dysfunction drugs has shown great efficacy in preventing male
erectile dysfunction. In order to help doctors know drug taken preference of
patients and better prescribe, it is crucial to analyze who actually take
erectile dysfunction drugs and the relation between sexual behaviors and drug
use. Existing clinical studies usually used descriptive statistics and regression
analysis based on small volume of data. In this paper, based on big volume of
data (48,630 questionnaires), we use data mining approaches besides statistics
and regression analysis to comprehensively analyze the relation between male
sexual behaviors and use of erectile dysfunction drugs for unravelling the
characteristic of patients who take erectile dysfunction drugs. We firstly
analyze the impact of multiple sexual behavior factors on whether to use the
erectile dysfunction drugs. Then, we explore to mine the Decision Rules for
Stratification to discover patients who are more likely to take drugs. Based on
the decision rules, the patients can be partitioned into four potential groups
for use of erectile dysfunction: high potential group, intermediate potential-1
group, intermediate potential-2 group and low potential group. Experimental
results show 1) the sexual behavior factors, erectile hardness and time length to
prepare (how long to prepares for sexual behaviors ahead of time), have bigger
impacts both in correlation analysis and potential drug taking patients
discovering; 2) odds ratio between patients identified as low potential and high
potential was 6.098 (95% confidence interval, 5.159-7.209) with statistically
significant differences in taking drug potential detected between all potential
groups.
PMID- 28423785
TI - Automated Identification of National Health Survey Research Topics in the
Academic Literature.
AB - National health surveys are routinely conducted to provide value data about a
country's health status and the health services being consumed by the population.
This information is used for surveillance, research, and the planning of
healthcare services at local and national levels. Although these national health
surveys are viewed as important resources for public and population health, there
is limited information as to the type of research being conducted with these
surveys. This study investigates, through the use of automated text data mining,
an approach to identify and collate the type of academic literature being
published using national health surveys.
PMID- 28423786
TI - Prevalence Estimation of Protected Health Information in Swedish Clinical Text.
AB - Obscuring protected health information (PHI) in the clinical text of health
records facilitates the secondary use of healthcare data in a privacy-preserving
manner. Although automatic de-identification of clinical text using machine
learning holds much promise, little is known about the relative prevalence of PHI
in different types of clinical text and whether there is a need for domain
adaptation when learning predictive models from one particular domain and
applying it to another. In this study, we address these questions by training a
predictive model and using it to estimate the prevalence of PHI in clinical text
written (1) in different clinical specialties, (2) in different types of notes
(i.e., under different headings), and (3) by persons in different professional
roles. It is demonstrated that the overall PHI density is 1.57%; however,
substantial differences exist across domains.
PMID- 28423787
TI - IT Infrastructure of an Oncological Trial Where Xenografts Inform Individual
Second Line Treatment Decision.
AB - Translational clinical research is often characterized by a unidirectional
information flow from clinical to molecular data by using phenotypes to elucidate
molecular disease processes. Here we present the RESIST study which uses
xenograft information for individual treatment decisions after resistance to a
specific anticancer treatment establishing a bidirectional information flow
between patient and molecular biology. The paper discusses the specific
challenges related to the IT infrastructure for such bidirectional translational
projects and proposes solutions. A specific focus is the safeguarding genomic
privacy.
PMID- 28423788
TI - Medical and Healthcare Curriculum Exploratory Analysis.
AB - In the recent years, medical and healthcare higher education institutions compile
their curricula in different ways in order to cover all necessary topics and
sections that the students will need to go through to success in their future
clinical practice. A medical and healthcare curriculum consists of many
descriptive parameters, which define statements of what, when, and how students
will learn in the course of their studies. For the purpose of understanding a
complicated medical and healthcare curriculum structure, we have developed a web
oriented platform for curriculum management covering in detail formal metadata
specifications in accordance with the approved pedagogical background, namely
outcome-based approach. Our platform provides a rich database that can be used
for innovative detailed educational data analysis. In this contribution we would
like to present how we used a proven process model as a way of increasing
accuracy in solving individual analytical tasks with the available data.
Moreover, we introduce an innovative approach on how to explore a dataset in
accordance with the selected methodology. The achieved results from the selected
analytical issues are presented here in clear visual interpretations in an
attempt to visually describe the entire medical and healthcare curriculum.
PMID- 28423789
TI - Using Electronic Health Records to Assess Depression and Cancer Comorbidities.
AB - Comorbid diseases are an important concern in oncology since they can affect the
choice and effectiveness of treatment. What is particularly relevant is the fact
that the diagnosis of depression in cancer patients has an important impact on
the quality of life of these patients. Although there is no consensus about a
specific relationship of depression with certain cancer types, some authors have
proposed that depression constitutes a risk factor for cancer. The objective of
this study is to identify the presence of comorbidities in a massive EHR system,
between depression and the 10 most common cancers in women and men and to
determine if there is a preferred temporal ordering in the co-occurrence of these
diseases. All the cancers studied showed a significant co-occurrence with
depression, more specifically, twice more frequent than what could be expected by
chance. A preferred directionality was identified between some of the comorbid
diseases, such as breast cancer followed by depression, and depression followed
by either stomach cancer, colorectal cancer or lung cancer. Future work will
address other potential factors that have an influence on the likelihood of
suffering from depression in patients with cancer, such as drug therapies
received, exposure to substance of abuse or other comorbidities.
PMID- 28423790
TI - Improving Terminology Mapping in Clinical Text with Context-Sensitive Spelling
Correction.
AB - The mapping of unstructured clinical text to an ontology facilitates meaningful
secondary use of health records but is non-trivial due to lexical variation and
the abundance of misspellings in hurriedly produced notes. Here, we apply several
spelling correction methods to Swedish medical text and evaluate their impact on
SNOMED CT mapping; first in a controlled evaluation using medical literature text
with induced errors, followed by a partial evaluation on clinical notes. It is
shown that the best-performing method is context-sensitive, taking into account
trigram frequencies and utilizing a corpus-based dictionary.
PMID- 28423791
TI - Medical Text Classification Using Convolutional Neural Networks.
AB - We present an approach to automatically classify clinical text at a sentence
level. We are using deep convolutional neural networks to represent complex
features. We train the network on a dataset providing a broad categorization of
health information. Through a detailed evaluation, we demonstrate that our method
outperforms several approaches widely used in natural language processing tasks
by about 15%.
PMID- 28423792
TI - Acronym Disambiguation in Spanish Electronic Health Narratives Using Machine
Learning Techniques.
AB - Electronic Health Records (EHRs) are now being massively used in hospitals what
has motivated current developments of new methods to process clinical narratives
(unstructured data) making it possible to perform context-based searches. Current
approaches to process the unstructured texts in EHRs are based in applying text
mining or natural language processing (NLP) techniques over the data. In
particular Named Entity Recognition (NER) is of paramount importance to retrieve
specific biomedical concepts from the text providing the semantic type of the
concept retrieved. However, it is very common that clinical notes contain lots of
acronyms that cannot be identified by NER processes and even if they are
identified, an acronym may correspond to several meanings, so disambiguation of
the found term is needed. In this work we provide an approach to perform acronym
disambiguation in Spanish EHR using machine learning techniques.
PMID- 28423793
TI - Automated Classification of Semi-Structured Pathology Reports into ICD-O Using
SVM in Portuguese.
AB - Pathology reports are a main source of information regarding cancer diagnosis and
are commonly written following semi-structured templates that include tumour
localisation and behaviour. In this work, we evaluated the efficiency of support
vector machines (SVMs) to classify pathology reports written in Portuguese into
the International Classification of Diseases for Oncology (ICD-O), a biaxial
classification of cancer topography and morphology. A partnership program with
the Brazilian hospital A.C. Camargo Cancer Center provided anonymised pathology
reports and structured data from 94,980 patients used for training and
validation. We employed SVMs with tf-idf weighting scheme in a bag-of-words
approach and report F1 score of 0.82 for 18 sites and 0.73 for 49 morphology
classes. With the largest dataset ever used in such a task, our work provides
reliable estimates for the classification of pathology reports in Portuguese and
agrees with a few similar studies published in the same kind of data in other
languages.
PMID- 28423794
TI - Informative Observation in Health Data: Association of Past Level and Trend with
Time to Next Measurement.
AB - In routine health data, risk factors and biomarkers are typically measured
irregularly in time, with the frequency of their measurement depending on a range
of factors - for example, sicker patients are measured more often. This is termed
informative observation. Failure to account for this in subsequent modelling can
lead to bias. Here, we illustrate this issue using body mass index measurements
taken on patients with type 2 diabetes in Salford, UK. We modelled the
observation process (time to next measurement) as a recurrent event Cox model,
and studied whether previous measurements in BMI, and trends in the BMI, were
associated with changes in the frequency of measurement. Interestingly, we found
that increasing BMI led to a lower propensity for future measurements. More
broadly, this illustrates the need and opportunity to develop and apply models
that account for, and exploit, informative observation.
PMID- 28423795
TI - Multivariate and Longitudinal Health System Indicators.
AB - Within population health information systems, indicators are commonly presented
as independent, cross-sectional measures, neglecting the multivariate,
longitudinal nature of disease progression, health care use, and profiles of
performance. We use administrative claims data of Montreal, Canada to identify
patterns across indicators and over time in chronic obstructive pulmonary disease
patients. We first cluster regions based on four health service indicators. Our
second approach discovers individual-level trajectories based on a hidden Markov
model using the same four indicators. Both approaches offer additional insights
by facilitating the discovery and interpretation of indicators, such as a dual
interpretation of low use of general practitioner services. These approaches to
the analysis and visualization of health indicators can provide a foundation for
information displays that will help decision makers identify areas of concern,
predict future disease burden, and implement appropriate policies.
PMID- 28423796
TI - Personalized Guideline-Based Treatment Recommendations Using Natural Language
Processing Techniques.
AB - Clinical guidelines and clinical pathways are accepted and proven instruments for
quality assurance and process optimization. Today, electronic representation of
clinical guidelines exists as unstructured text, but is not well-integrated with
patient-specific information from electronic health records. Consequently,
generic content of the clinical guidelines is accessible, but it is not possible
to visualize the position of the patient on the clinical pathway, decision
support cannot be provided by personalized guidelines for the next treatment
step. The Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT)
provides common reference terminology as well as the semantic link for combining
the pathways and the patient-specific information. This paper proposes a model
based approach to support the development of guideline-compliant pathways
combined with patient-specific structured and unstructured information using
SNOMED CT. To identify SNOMED CT concepts, a software was developed to extract
SNOMED CT codes out of structured and unstructured German data to map these with
clinical pathways annotated in accordance with the systematized nomenclature.
PMID- 28423797
TI - HTP-NLP: A New NLP System for High Throughput Phenotyping.
AB - Secondary use of clinical data for research requires a method to quickly process
the data so that researchers can quickly extract cohorts. We present two advances
in the High Throughput Phenotyping NLP system which support the aim of truly high
throughput processing of clinical data, inspired by a characterization of the
linguistic properties of such data. Semantic indexing to store and generalize
partially-processed results and the use of compositional expressions for
ungrammatical text are discussed, along with a set of initial timing results for
the system.
PMID- 28423799
TI - Global eHealth, Social Business and Citizen Engagement.
AB - The UNSW WHO Collaborating Centre (WHOCC) in eHealth was established in 2013. Its
designated activities are: mHealth and evidence-based evaluation, including use
case analyses. The UNSW Yunus Social Business Health Hub (YSBHH), established in
2015 to build on the Yunus Centre/Grameen Bank eHealth initiatives, added social
business and community participation dimensions to the UNSW global eHealth
program. The Grameen Bank is a social business built around microcredit, which
are small loans to poor people to enable them to "produce something, sell
something, earn something to develop self-reliance and a life of dignity". The
vision revolves around global partnerships for development, Millennium
Development Goals (MDGs) and Sustainable Development Goals (SDGs). The scope
includes mHealth implementation and evaluation in the context of the Internet of
Things (IoT), with a growing focus on social business and citizen engagement
approaches. This paper summarises a critical case study of the UNSW WHOCC
(eHealth) designated activities in collaboration with Bangladesh institutions
(International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDRB) and
Yunus Centre). Issues and challenges are highlighted.
PMID- 28423800
TI - Project PEACH at UCLH: Student Projects in Healthcare Computing.
AB - A collaboration between clinicians at UCLH and the Dept of Computer Science at
UCL is giving students of computer science the opportunity to undertake real
healthcare computing projects as part of their education. This is enabling the
creation of a significant research computing platform within the Trust, based on
open source components and hosted in the cloud, while providing a large group of
students with experience of the specific challenges of health IT.
PMID- 28423801
TI - Monitoring of Students' Interaction in Online Learning Settings by Structural
Network Analysis and Indicators.
AB - Learning as a constructive process works best in interaction with other learners.
Support of social interaction processes is a particular challenge within online
learning settings due to the spatial and temporal distribution of participants.
It should thus be carefully monitored. We present structural network analysis and
related indicators to analyse and visualize interaction patterns of participants
in online learning settings. We validate this approach in two online courses and
show how the visualization helps to monitor interaction and to identify activity
profiles of learners. Structural network analysis is a feasible approach for an
analysis of the intensity and direction of interaction in online learning
settings.
PMID- 28423802
TI - A Lens for Evaluating Genetic Information Governance Models: Balancing Equity,
Efficiency and Sustainability.
AB - This paper draws from the literature on collective action and the governance of
the commons to address the governance of genetic data on variants of specific
genes. Specifically, the data arrangements under study relate to the BRCA genes
(BRCA1 and BRCA2) which are linked to breast and ovarian cancer. These data are
stored in global genetic data repositories and accessed by researchers and
clinicians, from both public and private institutions. The current BRCA data
arrangements are fragmented and politicized as there are multiple tensions around
data ownership and sharing. Three key principles are proposed for forming and
evaluating data governance arrangements in the field. These principles are:
equity, efficiency and sustainability.
PMID- 28423803
TI - Business Rules to Improve Secondary Data Use of Electronic Healthcare Systems.
AB - The 'fit for purpose' paradigm used for data quality assessment in electronic
healthcare record (EHR) systems is not so fit when assessed in the light of
secondary data use. An analysis of the difficulties encountered in trying to use
existing EHR data for cohort identification for prospective clinical trials and
retrograde data analytics, revealed the root causes to fall in three categories:
(1) issues in workflow and data registration, (2) preventable inadequacies in
software configuration and personalization and (3) software development issues on
the side of the vendor. By reviewing secondary data use requirements and
formulating value adding business rules, development and data collection
practices can be steered towards greater value in secondary data consumption.
PMID- 28423804
TI - Facilitators and Barriers of Electronic Health Record Patient Portal Adoption by
Older Adults: A Literature Study.
AB - Patient portal usage by older adults, patients aged 50 years old and above, is
intended to improve their access and quality of care. Acceptance of patient
portals by this target group is low. This paper discusses the results of a
literature review to determine the facilitators and barriers that drive or
inhibit older patients to adopt patient portals. Articles were included when they
described an acceptance, adoption or usability evaluation study of a patient
portal. From a total of 245 potentially relevant articles, 8 articles were
finally included. We used the Unified Theory of Acceptance and Use of Technology
(UTAUT) as a classification model to analyze factors influencing older adults'
acceptance of patient portals. Main facilitators for acceptance were 'performance
expectancy' and 'voluntariness of use' related to a higher level of education and
experienced health. Main barriers were limited health literacy and motivation
related to involuntariness to use a patient portal. Poor facilitation conditions
(limited technology access and no prior knowledge on existence of a patient
portal) hampered access to a portal. More thorough insight into the latter is
needed to improve the reach and effectiveness of patient portals among older
patients.
PMID- 28423805
TI - Preventing Unintended Disclosure of Personally Identifiable Data Following
Anonymisation.
AB - Errors and anomalies during the capture and processing of health data have the
potential to place personally identifiable values into attributes of a dataset
that are expected to contain non-identifiable values. Anonymisation focuses on
those attributes that have been judged to enable identification of individuals.
Attributes that are judged to contain non-identifiable values are not considered,
but may be included in datasets that are shared by organisations. Consequently,
organisations are at risk of sharing datasets that unintendedly disclose
personally identifiable values through these attributes. This would have ethical
and legal implications for organisations and privacy implications for individuals
whose personally identifiable values are disclosed. In this paper, we formulate
the problem of unintended disclosure following anonymisation, describe the
necessary steps to address this problem, and discuss some key challenges to
applying these steps in practice.
PMID- 28423806
TI - Protecting Privacy of Genomic Information.
AB - The ISO/IEC committee in charge of standardizing the well-known MPEG audiovisual
standards has launched, in cooperation with the ISO committee on Biotechnology, a
new activity for efficient compressed storage and transmission of genomic
information. The paper presents proposals for adding privacy and security to such
in-progress standards.
PMID- 28423807
TI - Clinical Data Warehouse Watermarking: Impact on Syndromic Measure.
AB - Watermarking appears as a promising tool for the traceability of shared medical
databases as it allows hiding the traceability information into the database
itself. However, it is necessary to ensure that the distortion resulting from
this process does not hinder subsequent data analysis. In this paper, we present
the preliminary results of a study on the impact of watermarking in the
estimation of flu activities. These results show that flu epidemics periods can
be estimated without significant perturbation even when considering a moderate
watermark distortion.
PMID- 28423808
TI - Security Policy and Infrastructure in the Context of a Multi-Centeric Information
System Dedicated to Autism Spectrum Disorder.
AB - Autism spectrum disorders (ASD) are complex neuro-developmental disorders
affecting children in their early age. The diagnosis of ASD relies on
multidisciplinary investigations, in psychiatry, neurology, genetics,
electrophysiology, neuro-imagery, audiology and ophthalmology. In order to
support clinicians, researchers and public health decision makers, we designed an
information system dedicated to ASD, called TEDIS. TEDIS was designed to manage
systematic, exhaustive and continuous multi-centric patient data collection via
secured Internet connections. In this paper, we present the security policy and
security infrastructure we developed to protect ASD' patients' clinical data and
patients' privacy. We tested our system on 359 ASD patient records in a local
secured intranet environment and showed that the security system is functional,
with a consistent, transparent and safe encrypting-decrypting behavior. It is
ready for deployment in the nine ASD expert assessment centers in the Ile de
France district.
PMID- 28423809
TI - Use of a Nationwide Personally Controlled Electronic Health Record by Healthcare
Professionals and Patients: A Case Study with the French DMP.
AB - If the wide adoption of electronic health records (EHRs) is necessary to address
health information sharing and care coordination issues, it is not sufficient. In
order to address health information sharing, some countries, among which, France,
have implemented a centralized framework with "new" nationwide care records. The
French DMP is a centralized, nationally shared, electronic medical record,
created according to the opt-in model. More than five years after the launching
of the DMP project, DMPs have been created for 1.5% of the target population,
which demonstrates the poor adoption of the tool by healthcare professionals.
Among the 583,997 existing DMPs in June 2016, 41% were empty, and 24% of non
empty DMPs were actually accessed. If these "active" DMPs were equally accessed
by both healthcare professionals and patients, patients accessed DMP documents
four times more than healthcare professionals.
PMID- 28423810
TI - Use and Adaptation of Open Source Software for Capacity Building to Strengthen
Health Research in Low- and Middle-Income Countries.
AB - Health research capacity strengthening is of importance to reach health goals.
The ARCADE projects' aim was to strengthen health research across Africa and Asia
using innovative educational technologies. In the four years of the EU funded
projects, challenges also of technical nature were identified. This article
reports on a study conducted within the ARCADE projects. The study focused on
addressing challenges of video conferencing in resource constrained settings and
was conducted using action research. As a result, a plugin for the open source
video conferencing system minisip was implemented and evaluated. The study showed
that both the audio and video streams could be improved by the introduced plugin,
which addressed one technical challenge.
PMID- 28423811
TI - Connecting the Links: Narratives, Simulations and Serious Games in Prehospital
Training.
AB - Due to rapid and substantial changes in the health sector, collaboration and
supporting technologies get more into focus. Changes in education and training
are also required. Simulations and serious games (SSG) are often advocated as
promising technologies supporting training of many and in the same manner, or
increasing the skills necessary to deal with new, dangerous, complex or
unexpected situations. The aim of this paper is to illustrate and discuss
resources needed for planning and performing collaborative contextual training
scenarios. Based on a practical study involving prehospital nurses and different
simulator technologies the often-recurring activity chains in prehospital
training were trained. This paper exemplifies the benefit of using narratives and
SSGs for contextual training contributing to higher user experiences. The
benefits of using simulation technologies aligned by processes can be easier
defined by narratives from practitioners. While processes help to define more
efficient and effective training, narratives and SSGs are beneficial to design
scenarios with clues for higher user experiences. By discussing illustrative
examples, the paper contributes to better understanding of how to plan simulation
technology rich training scenarios.
PMID- 28423812
TI - Designing an E-Learning Platform for Postoperative Arthroplasty Adverse Events.
AB - This paper presents a mobile software application development for e-learning
based on the adverse events data within the field of arthroplasty. The
application aims at providing a learning platform for physicians, patients, and
medical students. Design of user interface aims to meet requirements of several
user groups concerned with the adverse events of the knee and hip implants.
Besides the clinical patient data, the platform wants to include even electronic
patient data as a result of self-monitoring. Two different modules were created,
one for medical staff and one for patients, both divided into the knee and hip
areas. Knowledge is represented in forms of statistics, treatment options, and
detailed, actual adverse event reports. Patients are given a choice of
recommendation for two main situations: 'about your diagnosis', and 'what if you
get a problem' as advice and guidance during the postoperative rehabilitation.
Expert evaluation resulted in acceptance of the concept and provided feedback
ideas. The patient evaluation has also been positive. Implementation will mean
that a high-fidelity prototype will be developed and tested in larger user groups
(medical staff, patients).
PMID- 28423813
TI - Understanding the Context of Learning in an Online Social Network for Health
Professionals' Informal Learning.
AB - Online social networks (OSN) enable health professionals to learn informally, for
example by sharing medical knowledge, or discussing practice management
challenges and clinical issues. Understanding the learning context in OSN is
necessary to get a complete picture of the learning process, in order to better
support this type of learning. This study proposes critical contextual factors
for understanding the learning context in OSN for health professionals, and
demonstrates how these contextual factors can be used to analyse the learning
context in a designated online learning environment for health professionals.
PMID- 28423814
TI - Ubiquitous Adoption of Innovative and Supportive Information and Communications
Technology Across Health and Social Care Needs Education for Clinicians.
AB - The paper presents the development, use and evaluation of an on-line
undergraduate module delivering an academic-led programme of eHealth learning
within nursing, midwifery, allied health professional and social work courses.
The health information technology competency frameworks are explored along with
an overview of the resulting module. The need for an academically led module will
be made along with a description of the management required to maintain validity
of content materials. A review of student evaluations will be presented. In
conclusion the positive change in attitude and understanding of academic staff
members towards health information technology through the inclusion of the module
across all of the undergraduate courses will be explored.
PMID- 28423815
TI - Mobile Medical Apps and mHealth Devices: A Framework to Build Medical Apps and
mHealth Devices in an Ethical Manner to Promote Safer Use - A Literature Review.
AB - This paper presents a preliminary literature review in the area of ethics in the
development of Mobile Medical Apps and mHealth. The review included both direct
health apps and also apps marketed under the area of well-being in addition to
mHealth devices. The following words and combinations of them were used to carry
out the search for publications, mHealth, Apps, Ethics. The search engines used
were Google Scholar, and PubMed. The paper is restricted to publications since
2012. The total number of papers found was 1,920 of which 84 were reviewed. The
reason for so few being reviewed was that the majority only considered security.
The search revealed many papers dealing with security for all types of apps and
mHealth devices but there are very few papers dealing with the ethical issues
related to Apps or mHealth devices in the area. It is noted however that the
number of apps is increasing in number exponentially and therefore it is argued
that it is necessary to pay attention to the ethical aspects. There are now
estimated to be 165,000 apps available in this area. How ethics are addressed in
health and well-being apps is important as they can have an effect on the health
of the individual using them. In a similar way, the need for addressing ethical
issues for development of well-being apps is evident. In a study [1] it was noted
that even though Electronic Health Record (EHR) was the highest ranked tablet
related task only one third of clinicians said that EHR was optimized for
smartphones. When apps are integrated with the EHR they fully optimize
productivity. In the same study the significant challenges identified included
the method of evaluation and selection of mobile health solutions in order to
ensure that clinical outcomes, care and efficiency are included. Security is
mentioned but again wider ethical issues were not a consideration. From the
literature review it is clear that there is a need for guidelines for how
developers of medical ad well-being apps and mHealth devices should address
ethical issues during development, and the generation of these guidelines is the
subject of ongoing research by the authors.
PMID- 28423816
TI - A Method for Co-Designing Theory-Based Behaviour Change Systems for Health
Promotion.
AB - A methodology was defined and developed for designing theory-based behaviour
change systems for health promotion that can be tailored to the individual.
Theories from two research fields were combined with a participatory action
research methodology. Two case studies applying the methodology were conducted.
During and between group sessions the participants created material and designs
following the behaviour change strategy themes, which were discussed, analysed
and transformed into a design of a behaviour change system. Theories in
behavioural change and persuasive technology guided the data collection, data
analyses, and the design of a behaviour change system. The methodology has strong
emphasis on the target group's participation in the design process. The different
aspects brought forward related to behaviour change strategies defined in
literature on persuasive technology, and the dynamics of these are associated to
needs and motivation defined in literature on behaviour change. It was concluded
that the methodology aids the integration of theories into a participatory action
research design process, and aids the analyses and motivations of design choices.
PMID- 28423817
TI - Persona Development and Educational Needs to Support Informal Caregivers.
AB - Informal caregivers are playing an increasing role in community based care
delivery. Research is needed that looks at the educational needs of informal
caregivers as a precursor to HIT design to support community care delivery. A
challenge is informal caregivers have very diverse educational needs. Personas
are an approach to describe user characteristics as part of systems design and
this approach could be used to understand and categorize the various educational
needs of informal caregivers. This paper addresses this research need and
provides a method for persona development and the identification of educational
needs for informal caregivers.
PMID- 28423818
TI - An Approach for Enhancing Adoption, Use and Utility of Shared Digital Health
Records in Rural Australian Communities.
AB - Internationally, shared digital health records are considered an important
addition to improving modern health care provision. Australia launched its
version, My Health Record (MyHR), in 2012 but has experienced low adoption and
challenges in practical implementation and evaluation. Individuals living with
complex and chronic conditions in rural and remote communities often experience
challenges in obtaining equitable access to health care provision. They are also
supposed to face additional barriers to adopting and using eHealth services. This
paper reports on research investigating adoption, use and utility of MyHR, in
rural remote Australian community settings. Based on this research an approach
for improving national roll out of MyHR is presented. The approach highlights a
means to understand and engage communities with complex care needs, to support
their adoption and use of digital tools. It also draws attention to holistic
methods for evaluating and assessing impact at individual, community and health
care provision levels.
PMID- 28423819
TI - Exploring Innovation Capabilities of Hospital CIOs: An Empirical Assessment.
AB - Hospital CIOs play a central role in the adoption of innovative health IT. Until
now, it remained unclear which particular conditions constitute their capability
to innovate in terms of intrapersonal as well as organisational factors. An
inventory of 20 items was developed to capture these conditions and examined by
analysing data obtained from 164 German hospital CIOs. Principal component
analysis resulted in three internally consistent components that constitute large
portions of the CIOs innovation capability: organisational innovation culture,
entrepreneurship personality and openness towards users. Results were used to
build composite indicators that allow further evaluations.
PMID- 28423820
TI - The Invisibility of Disadvantage: Why Do We Not Notice?
AB - Personal health records (PHRs) offer tantalising benefits for patients and
healthcare providers, including improvements in patient-provider communication,
patient empowerment, and access to data and information. A suspicion that
disadvantaged patients are less likely to use or benefit from PHRs stimulated a
research agenda that included: (a) a literature review; and (b) empirical
analysis of eight years' hospital admission and discharge data linked to measures
of patient social disadvantage. The results demonstrated an association between
disadvantage, increased use of public hospital services and barriers to PHR use.
These findings may appear self-evident, but dramatically highlight how
disadvantaged patients continue to be overlooked in many e-health design
processes, and are rarely a focus of user centred design. The paper concludes by
briefly considering the implications of this invisibility.
PMID- 28423821
TI - Using Healthcare Work Process Modelling in Hospitals to Increase the Fit Between
the Healthcare Workflow and the Electronic Medical Record.
AB - As with other organizations, hospitals tend to promote unrealistic expectations
related to software implementaton. Quite often the real issue is a misfit between
the software and organizational factors. Our paper shows how work process
modelling within the hospital can reduce this misfit according to the vision
developped by the ergonomics and the management of information systems. This idea
is supported by two cases in two different University Hospitals in France, in
which using work process modelling lead to identification of problems and their
causes, and solutions. Modelling requires time, which may be considered costly by
senior hospital managers, but also should be considered as an investment in order
to achieve expected goals.
PMID- 28423823
TI - Reference Architecture Model Enabling Standards Interoperability.
AB - Advanced health and social services paradigms are supported by a comprehensive
set of domains managed by different scientific disciplines. Interoperability has
to evolve beyond information and communication technology (ICT) concerns,
including the real world business domains and their processes, but also the
individual context of all actors involved. So, the system must properly reflect
the environment in front and around the computer as essential and even defining
part of the health system. This paper introduces an ICT-independent system
theoretical, ontology-driven reference architecture model allowing the
representation and harmonization of all domains involved including the
transformation into an appropriate ICT design and implementation. The entire
process is completely formalized and can therefore be fully automated.
PMID- 28423824
TI - Querying Archetype-Based Electronic Health Records Using Hadoop and Dewey
Encoding of openEHR Models.
AB - Archetype-based Electronic Health Record (EHR) systems using generic reference
models from e.g. openEHR, ISO 13606 or CIMI should be easy to update and
reconfigure with new types (or versions) of data models or entries, ideally with
very limited programming or manual database tweaking. Exploratory research (e.g.
epidemiology) leading to ad-hoc querying on a population-wide scale can be a
challenge in such environments. This publication describes implementation and
test of an archetype-aware Dewey encoding optimization that can be used to
produce such systems in environments supporting relational operations, e.g. RDBMs
and distributed map-reduce frameworks like Hadoop. Initial testing was done using
a nine-node 2.2 GHz quad-core Hadoop cluster querying a dataset consisting of
targeted extracts from 4+ million real patient EHRs, query results with sub
minute response time were obtained.
PMID- 28423825
TI - HEMIC Project: Design of a Clinical Information Modelling Tool Based on ISO13972
Technical Specification.
AB - The Andalusian Health Service is the public healthcare provider for 8.302.923
inhabitants in the South Spain. This organization coordinates primary and
specialized care with an IT infrastructure composed by multiple Electronic Health
Record Systems. According to the large volume of healthcare professionals
involved, there is a need for providing a consistent management of information
through multiple locations and systems. The HEMIC project aims to address this
need developing and validating a methodology based on a software tool for
standardizing information contained within EHR systems. The developed tool has
been designed for supporting the participation of healthcare professionals the
establishment of mechanisms for information governance. This research presents
the requirements and designs for of a software tool focused on the adoption of
recognized best practice in clinical information modeling. The designed tool has
a Service Oriented Architecture that will be able to integrate terminology
servers and repositories of clinical information models as part of the modeling
process. Moreover, the defined tool organizes clinicians, IT developers and
terminology experts involved in the modeling process in three levels to promote
their coordination in the definition, specialization and validation of clinical
information models. In order to ensure the quality of the developed clinical
information models, the defined tool is based on the requirements defined in the
ISO13972 Technical Specification.
PMID- 28423826
TI - Combining Archetypes, Ontologies and Formalization Enables Automated Computation
of Quality Indicators.
AB - ArchMS is a framework that represents clinical information and knowledge using
ontologies in OWL, which facilitates semantic interoperability and thereby the
exploitation and secondary use of clinical data. However, it does not yet support
the automated assessment of quality of care. CLIF is a stepwise method to
formalize quality indicators. The method has been implemented in the CLIF tool
which supports its users in generating computable queries based on a patient data
model which can be based on archetypes. To enable the automated computation of
quality indicators using ontologies and archetypes, we tested whether ArchMS and
the CLIF tool can be integrated. We successfully automated the process of
generating SPARQL queries from quality indicators that have been formalized with
CLIF and integrated them into ArchMS. Hence, ontologies and archetypes can be
combined for the execution of formalized quality indicators.
PMID- 28423827
TI - Parallel Design of Browsing Scheme and Data Model for Multi-Level Hierarchical
Application Devoted to Management of Patient with Infectious Disease in Primary
Care.
AB - Many decision systems are based on a hierarchical approach, enriching the known
context used to finally choose the right potential action. Designing the scheme
for browsing the clinical guidelines is a task devoted to expert in infectious
diseases. Designing the data model is a task devoted to the expert in data
modeling. As a consequence, browsing scheme and data model generally differ in
terms of abstraction levels. While the browsing scheme proposes to navigate into
depth, the data model stays flat. We propose here a novel method to design in
parallel the browsing scheme and the data model so that both of them reflect the
different abstraction levels in decision process.
PMID- 28423828
TI - Preliminary Analysis of the OBO Foundry Ontologies and Their Evolution Using
OQuaRE.
AB - The biomedical community has now developed a significant number of ontologies.
The curation of biomedical ontologies is a complex task as they evolve rapidly,
being new versions regularly published. Therefore, methods to support ontology
developers in analysing and tracking the evolution of their ontologies are
needed. OQuaRE is an ontology evaluation framework based on quantitative metrics
that permits to obtain normalised scores for different ontologies. In this work,
OQuaRE has been applied to 408 versions of the eight OBO Foundry member
ontologies. The OBO Foundry member ontologies are supposed to have been built by
applying the OBO Foundry principles. Our results show that this set of ontologies
is actually following principles such as the naming convention, and that the
evolution of the OBO Foundry member ontologies is generating ontologies with
higher OQuaRE quality scores.
PMID- 28423829
TI - Ontological Realism for the Research Domain Criteria for Mental Disorders.
AB - At the heart of the Research Domain Criteria for Mental Disorders is a matrix in
which functional aspects of behavior are related to genotypic and (endo
)phenotypic research findings, and the various techniques through which they can
been observed. The matrix is work in progress. As such it currently suffers from
several shortcomings, the resolution of which, we contend, are essential to
success of NIMH's goal of fostering translational science on mental disorders.
Using well-established criteria for assessing the terminological and ontological
quality of biomedical representations we identified the major problems to be (1)
the abundant presence of terms that lack face value, (2) the absence of what the
exact nature of the represented relationships are, and (3) referential
imprecision with respect to the intended granularity of what the terms denote. We
propose to eliminate these shortcomings by resorting to definitions and formal
representations under the umbrella of Ontological Realism as they already have
been developed in the areas of mental health, anatomy and biological functions.
PMID- 28423830
TI - Bridging the Semantic Gap Between Diagnostic Histopathology and Image Analysis.
AB - With the wider acceptance of Whole Slide Images (WSI) in histopathology domain,
automatic image analysis algorithms represent a very promising solution to
support pathologist's laborious tasks during the diagnosis process, to create a
quantification-based second opinion and to enhance inter-observer agreement. In
this context, reference vocabularies and formalization of the associated
knowledge are especially needed to annotate histopathology images with labels
complying with semantic standards. In this work, we elaborate a sustainable
triptych able to bridge the gap between pathologists and image analysis
scientists. The proposed paradigm is structured along three components: i)
extracting a relevant semantic repository from the College of American
Pathologists (CAP) organ-specific Cancer Checklists and associated Protocols
(CC&P); ii) identifying imaging formalized knowledge issued from effective
histopathology imaging methods highlighted by recent Digital Pathology (DP)
contests and iii) proposing a formal representation of the imaging concepts and
functionalities issued from major biomedical imaging software (MATLAB, ITK,
ImageJ). Since the first step i) has been the object of a recent publication of
our team, this study focuses on the steps ii) and iii). Our hypothesis is that
the management of available semantic resources concerning the histopathology
imaging tasks associated with effective methods highlighted by the recent DP
challenges will facilitate the integration of WSI in clinical routine and support
new generation of DP protocols.
PMID- 28423831
TI - The BioTop Family of Upper Level Ontological Resources for Biomedicine.
AB - BioTop is a domain upper level ontology for the life sciences, based on OWL DL,
introduced ten years ago. This paper provides an update of the current state of
this resource, with a special focus on BioTop's top level, BioTopLite, which
currently contains 55 classes, 37 object properties and 247 description logics
axioms. A bridging file allows harmonising BioTopLite with the classes of Basic
Formal Ontology BFO2. The updated OWL resources are available at
http://purl.org/biotop. They build the core of several upper level ontological
artefacts including bridging ontologies to other upper level resources.
PMID- 28423832
TI - Building SNOMED CT Post-Coordinated Expressions from Annotation Groups.
AB - SNOMED CT supports post-coordination, a technique to combine clinical concepts to
ontologically define more complex concepts. This technique follows the validity
restrictions defined in the SNOMED CT Concept Model. Pre-coordinated expressions
are compositional expressions already in SNOMED CT, whereas post-coordinated
expressions extend its content. In this project we aim to evaluate the
suitability of existing pre-coordinated expressions to provide the patterns for
composing typical clinical information based on a defined list of sets of
interrelated SNOMED CT concepts. The method produces a 9.3% precision and a 95.9%
recall. As a consequence, further investigations are needed to develop heuristics
for the selection of the most meaningful matched patterns to improve the
precision.
PMID- 28423833
TI - HL7 FHIR: Ontological Reinterpretation of Medication Resources.
AB - "A solid ontology-based analysis with a rigorous formal mapping for correctness"
is one of the ten reasons why the HL7 standard Fast Healthcare Interoperability
Resources (FHIR) is advertised to be better than other standards for EHR
interoperability. In this paper, we aim at contributing to this formal analysis
by proposing an RDF representation of a subset of FHIR resources based on a
highly constrained top-level ontology and guided by the use of a set of Content
Ontology Design Patterns (Content ODPs) for representing clinical information. We
exemplify this by reinterpreting FHIR medication resources. Although a manual
task now, we foresee a possible automatic translation by using RDF shapes.
PMID- 28423834
TI - Communication of Children Symptoms in Emergency: Classification of the
Terminology.
AB - The significant part of non-urgent visits to the emergency highlight the
necessity to advise people on the actions to take according to their symptoms.
Although information sources are accessible through different channels their
content often employs medical terminologies that are difficult to understand by
laypersons. Our goal is to provide a terminology of the most common symptoms in
pediatric emergency adapted to laypersons. This terminology is organized in a
hierarchy by the mean of a card-sorting study. The resulting classification
separates the symptoms into two main categories: "accident" and "illness" that
are subdivided in 9 and 10 sub-categories. The study also revealed that some
symptoms were not understood by the participants and had to be reformulated,
confirming the importance of user-centered method. The classification resulting
from this study will be evaluated through a tree-test.
PMID- 28423835
TI - SNOMED CT as Reference Terminology in the Danish National Home Care Documentation
Standard.
AB - In Danish home care, multiple professions deliver services to citizens. FSIII is
a national home care documentation standard, where one of the goals is to share
documentation to improve coordination between these professional groups and avoid
double documentation. The aim of this study was to develop a SNOMED-CT based
navigation hierarchy to ensure that professions could preserve their
documentation practice, to help avoid double documentation, and to ensure that
the technical implementation did not require sophisticated semantic tools. The
method involved mapping of non-SNOMED-CT content to SNOMED CT, visualization of
merged graphs, identification of reference concepts, relating reference concepts
to the documentation models of each profession, and representation of the
navigation hierarchy in a reference set. The navigation hierarchy ensures that
citizen conditions appear in a relevant context, regardless of which profession
entered the data. Our approach paves the way for incremental standardization
projects, where an implementation artefact, such as the navigation hierarchy,
highlights the semantic features of SNOMED CT that can be used to reach specific
business goals; in this case, sharing data across professional groups.
PMID- 28423836
TI - Piloting a Collaborative Web-Based System for Testing ICD-11.
AB - BACKGROUND: The 11th revision of the International Classification of
Diseases (ICD-11), for the first time in ICD history, deployed web-based
collaboration of experts and ICT tools. To ensure that ICD-11 is working well, it
needs to be systematically field tested in different settings, across the world.
This will be done by means of a number of experiments. In order to support its
implementation, a web-based system (ICDfit) has been designed and developed. The
present paper illustrates the current prototype of the system and its technical
testing. METHODS: the system has been designed according to WHO requirements, and
implemented using PHP and MySQL. Then, a preliminary technical test has been
designed and run in January 2016, involving 8 users. They had to carry out double
coding, that is, coding case summaries with both ICD-10 and ICD-11, and answering
quick questions on the coding difficulty. RESULTS: the 8 users coded 632 cases
each, spending an average of 163 seconds per case. While we found an issue in the
mechanism used to record coding times, no further issues were found. CONCLUSION:
the proposed system seems to be technically adequate for supporting future ICD-11
testing.
PMID- 28423838
TI - Computable Information Governance Contracts.
AB - The risks of relinquishing control of electronic healthcare data for re-use in
research are mitigated by the use of data sharing agreements and information
governance procedures. These exist as legal, or quasi-legal, textual documents
exchanged between data owners. Their existence outside of the digital realm leads
to a situation where breaches of an agreement can only be detected and acted on
post-hoc. We introduce the design of a system of computable contracts, specified
formally, that can enforce the rules of data sharing agreements within the bounds
of electronic health care systems.
PMID- 28423837
TI - A Terminology in General Practice/Family Medicine to Represent Non-Clinical
Aspects for Various Usages: The Q-Codes.
AB - The hereby proposed terminology called "Q-Codes" can be defined as an extension
of the International Classification of Primary Care (ICPC-2). It deals with non
clinical concepts that are relevant in General Practice/Family Medicine (GP/FM).
This terminology is a good way to put an emphasis on underestimated topics such
as Teaching, Patient issues or Ethics. It aims at indexing GP/FM documents such
as congress abstracts and theses to get a more comprehensive view about the GP/FM
domain. The 182 identified Q-Codes have been very precisely defined by a college
of experts (physicians and terminologists) from twelve countries. The result is
available on the Health Terminology/Ontology Portal (http://www.hetop.org/Q) and
formatted in OWL-2 for further semantic considerations and will be used to index
the 2016 WONCA World congress communications.
PMID- 28423839
TI - A Semantic Framework for Logical Cross-Validation, Evaluation and Impact Analyses
of Population Health Interventions.
AB - Most chronic diseases are a result of a complex web of causative and correlated
factors. As a result, effective public health or clinical interventions that
intend to generate a sustainable change in these diseases most often use a
combination of strategies or programs. To optimize comparative effectiveness
evaluations and select the most efficient intervention(s), stakeholders (i.e.
public health institutions, policy-makers and advocacy groups, practitioners,
insurers, clinicians, and researchers) need access to reliable assessment
methods. Building on the theory of Evidence-Based Public Health (EBPH) we
introduce a knowledge-based framework for evaluating the consistency and
effectiveness of public health programs, interventions, and policies. We use a
semantic inference model that assists decision-makers in finding inconsistencies,
identifying selection and information biases, and with identifying confounding
and hidden dependencies in different public health programs and interventions.
The use of formal ontologies for automatic evaluation and assessment of public
health programs improves program transparency to stakeholders and decision
makers, which in turn increases buy-in and acceptance of methods, connects
multiple evaluation activities, and strengthens cost analysis.
PMID- 28423840
TI - Discovering Central Practitioners in a Medical Discussion Forum Using Semantic
Web Analytics.
AB - The aim of this paper is to investigate semantic web based methods to enrich and
transform a medical discussion forum in order to perform semantics-driven social
network analysis. We use the centrality measures as well as semantic similarity
metrics to identify the most influential practitioners within a discussion forum.
The centrality results of our approach are in line with centrality measures
produced by traditional SNA methods, thus validating the applicability of
semantic web based methods for SNA, particularly for analyzing social networks
for specialized discussion forums.
PMID- 28423841
TI - Towards an Open Infrastructure for Relating Scholarly Assets.
AB - Discovery of useful relationships between scholarly assets on the web is
challenging, both in terms generating the right metadata around the assets, and
in connecting all relevant digital entities in chain of provenance accessible to
the whole community. This paper reports the development of a framework and tools
enabling scholarly asset relationships to be expressed in a standard and open
way, illustrated with use-cases of discovering new knowledge across cohort
studies. The framework uses Research Objects for aggregation, distributed
databases for storage, and distributed ledgers for provenance. Our proposal
avoids management by a single central platform or organization, instead
leveraging the use of existing resources and platforms across natural
partnerships. Our proposed infrastructure will support a wide range of users from
system administrators to researchers.
PMID- 28423842
TI - Architecture and Initial Development of a Digital Library Platform for Computable
Knowledge Objects for Health.
AB - Throughout the world, biomedical knowledge is routinely generated and shared
through primary and secondary scientific publications. However, there is too much
latency between publication of knowledge and its routine use in practice. To
address this latency, what is actionable in scientific publications can be
encoded to make it computable. We have created a purpose-built digital library
platform to hold, manage, and share actionable, computable knowledge for health
called the Knowledge Grid Library. Here we present it with its system
architecture.
PMID- 28423843
TI - An Approach for the Support of Semantic Workflows in Electronic Health Records.
AB - With the unprecedented increase of healthcare data, technologies need to be both,
highly efficient for the meaningful utilization of accessible data and flexible
to adapt to future challenges and individual preferences. The OntoHealth system
makes use of semantic technologies to enable flexible and individual interaction
with Electronic Health Records (EHR) for physicians. This is achieved by the
execution of formally modelled clinical workflows and the composition of Semantic
Web Services (SWS). Several seamless components provide a service-oriented
structure defined by individual designed EHR-workflows. This work gives an
overview of the planned architecture and its main components. The architecture
constitutes the basis for the prototype implementation of all components. With
its highly dynamic structure based on SWS, the architecture will be able to cope
with both, the individual users' needs as well as the quick evolving healthcare
domain.
PMID- 28423844
TI - Identifying Emerging Trends in Medical Informatics: A Synthesis Approach.
AB - Medical informatics is a young and rapidly evolving field, influenced by and
impacting on many different knowledge domains. Recent contributions on scoping
the associated body of knowledge are confounded both by variations in popular use
of terminology for established areas, and by the advent of new areas without yet
established terminology. Determining the scope of a topic through online
bibliographic search filters is a well-established approach in scientific
research and has been developed as a human-directed task. Establishing the best
approach and automating the process has proved a difficult problem. This paper
explores the use of text analysis of bibliographic information using available
search engines and NVIVO text analysis tools to test the potential for dynamic
word based filters based on data mining. Results show that word searches of
abstracts are more effective than topic searches for identifying health
informatics papers, however more work is required to refine search terms to
improve generalisability. Using data mining to track changes in word use in
medical informatics journals, may make it possible to establish a more dynamic
search filter to match the evolving nature of the field of health informatics.
PMID- 28423845
TI - Appraising Healthcare Delivery Provision: A Framework to Model Business
Processes.
AB - Children are dependent on a reliable healthcare system, especially for the
delivery of care which crosses the primary/secondary care boundary. A methodology
based on UML has been developed to capture and single out meaningful parts of the
child healthcare pathways in order to facilitate comparison among 30 EU countries
within the MOCHA project. A first application of this methodology has been
reported considering asthma management as an example.
PMID- 28423846
TI - A Case Study on Sepsis Using PubMed and Deep Learning for Ontology Learning.
AB - We investigate the application of distributional semantics models for
facilitating unsupervised extraction of biomedical terms from unannotated
corpora. Term extraction is used as the first step of an ontology learning
process that aims to (semi-)automatic annotation of biomedical concepts and
relations from more than 300K PubMed titles and abstracts. We experimented with
both traditional distributional semantics methods such as Latent Semantic
Analysis (LSA) and Latent Dirichlet Allocation (LDA) as well as the neural
language models CBOW and Skip-gram from Deep Learning. The evaluation conducted
concentrates on sepsis, a major life-threatening condition, and shows that Deep
Learning models outperform LSA and LDA with much higher precision.
PMID- 28423847
TI - Acquisition of Expert/Non-Expert Vocabulary from Reformulations.
AB - Technical medical terms are complicated to be correctly understood by non
experts. Vocabulary, associating technical terms with layman expressions, can
help in increasing the readability of technical texts and their understanding.
The purpose of our work is to build this kind of vocabulary. We propose to
exploit the notion of reformulation following two methods: extraction of
abbreviations and of reformulations with specific markers. The segments
associated thanks to these methods are aligned with medical terminologies. Our
results allow to cover over 9,000 medical terms and show precision of extractions
between 0.24 and 0.98. The results and analyzed and compared with the existing
work.
PMID- 28423849
TI - Design of a Visual Interface for Comparing Antibiotics Using Rainbow Boxes.
AB - Non-optimal prescriptions of antibiotics have a negative impact on patients and
population. Clinical practice guidelines are not always followed by doctors
because the rationale of the recommendations is not always clear and can be
difficult to understand. In this paper, we propose a new approach consisting in
presenting the properties of antibiotics for allowing doctors to compare them and
choose the most appropriate one. For that, we used and extended rainbow boxes, a
new technique for overlapping set visualization. We tested our approach on 11
clinical situations related to urinary infections, and assessed the simplicity,
the interest and utility with 11 doctors. 10 of them found that this approach was
interesting and useful in clinical practice. Further studies are needed to
confirm this preliminary work.
PMID- 28423850
TI - A Method for Estimating the Risk Associated with Delaying Initial Treatment in
Breast Cancer.
AB - Over the past twenty-five years the time from diagnosis of breast cancer to the
initiation of therapy has steadily grown. In this note we present a mechanism to
give a ballpark estimate of the risk associated with delaying therapy given a
specific set of presenting patient data.
PMID- 28423851
TI - A Standardized and Data Quality Assessed Maternal-Child Care Integrated Data
Repository for Research and Monitoring of Best Practices: A Pilot Project in
Spain.
AB - We present the results of a pilot project of the Spanish Ministry of Health,
Social Services and Equality, envisaged to the development of a national
integrated data repository of maternal-child care information. Based on health
information standards and data quality assessment procedures, the developed
repository is aimed to a reliable data reuse for (1) population research and (2)
the monitoring of healthcare best practices. Data standardization was provided by
means of two main ISO 13606 archetypes (composed of 43 sub-archetypes), the first
dedicated to the delivery and birth information and the second about the infant
feeding information from delivery up to two years. Data quality was assessed by
means of a dedicated procedure on seven dimensions including completeness,
consistency, uniqueness, multi-source variability, temporal variability,
correctness and predictive value. A set of 127 best practice indicators was
defined according to international recommendations and mapped to the archetypes,
allowing their calculus using XQuery programs. As a result, a standardized and
data quality assessed integrated data respository was generated, including 7857
records from two Spanish hospitals: Hospital Virgen del Castillo, Yecla, and
Hospital 12 de Octubre, Madrid. This pilot project establishes the basis for a
reliable maternal-child care data reuse and standardized monitoring of best
practices based on the developed information and data quality standards.
PMID- 28423852
TI - Using the MRC Framework for Complex Interventions to Develop Clinical Decision
Support: A Case Study.
AB - The Medical Research Council (MRC) framework for complex interventions provides
useful guidance to assist with the development and evaluation of health
technology interventions such as decision support. In this paper we briefly
summarise a project that focused on designing a decision support intervention to
assist with the recognition, assessment and management of pain in patients with
dementia in an acute hospital setting. We reflect on our experience of using the
MRC framework to guide our study design, and highlight the importance of
considering decision support interventions as complex interventions.
PMID- 28423853
TI - Square2 - A Web Application for Data Monitoring in Epidemiological and Clinical
Studies
AB - Valid scientific inferences from epidemiological and clinical studies require
high data quality. Data generating departments therefore aim to detect data
irregularities as early as possible in order to guide quality management
processes. In addition, after the completion of data collections the obtained
data quality must be evaluated. This can be challenging in complex studies due to
a wide scope of examinations, numerous study variables, multiple examiners,
devices, and examination centers. This paper describes a Java EE web application
used to monitor and evaluate data quality in institutions with complex and
multiple studies, named Square2. It uses the Java libraries Apache MyFaces 2,
extended by BootsFaces for layout and style. RServe and REngine manage calls to R
server processes. All study data and metadata are stored in PostgreSQL. R is the
statistics backend and LaTeX is used for the generation of print ready PDF
reports. A GUI manages the entire workflow. Square2 covers all steps in the data
monitoring workflow, including the setup of studies and their structure, the
handling of metadata for data monitoring purposes, selection of variables, upload
of data, statistical analyses, and the generation as well as inspection of
quality reports. To take into account data protection issues, Square2 comprises
an extensive user rights and roles concept.
PMID- 28423854
TI - Exploring the Notion of Hazards for Health IT.
AB - Safety analysis is centred on identifying a set of hazards that form the basis of
risk assessment. In healthcare, hazards are potential sources of harm to patients
and as such the risk of these has to be assessed and managed. With the increased
reliance on Health IT systems in health and social care settings, some of these
hazards are associated with the development and use of these systems. In this
paper we examine current practices in hazard identification, focusing on how
clinicians and engineers approach this task within the Health IT safety assurance
process. We highlight certain technical and organisational challenges and discuss
approaches to improving current practices and promoting learning initiatives.
PMID- 28423855
TI - EHR Improvement Using Incident Reports.
AB - This paper discusses reactive improvement of clinical software using methods for
incident analysis. We used the "Five Whys" method because we had only descriptive
data and depended on a domain expert for the analysis. The analysis showed that
there are two major root causes for EHR software failure, and that they are
related to human and organizational errors. A main identified improvement is
allocating more resources to system maintenance and user training.
PMID- 28423856
TI - Improving Handovers Between Hospitals and Primary Care: Implementation of E
Messages and the Importance of Training.
AB - The transfer of information and responsibility for care of a patient from one
healthcare provider to another is referred to as a handover. While some handovers
are effective and achieve high quality communication, others represent a barrier
to continuity of care. To increase the patient safety, Norway decided to replace
handovers with an electronic e-message system (EMS). This paper refers to a
quantitative study of this implementation and examines the opinions of first-line
leaders and nurses (N = 108) on how organisational factors were taken into
account and how the implementation might be improved. The findings indicate that
such factors generally did not receive very much attention in the implementation
of the EMS, and less for the nurses than for the first-line leaders.
Particularly, the factor most prominently identified by both groups as warranted
improvement, was the training.
PMID- 28423857
TI - The Association Between the STOPP/START Criteria and Gastro-Intestinal Track
Bleedings in Elderly Patients.
AB - Potentially inappropriate prescribing is a common problem, especially in elderly
care. To tackle this problem, Irish medical experts have developed a list of
criteria when medication should be added or omitted based upon the patient's
physical condition and medication use, known as the STOPP and START criteria. The
STOPP and START criteria have been formulated to identify the prescribing of
potentially inappropriate medicines (PIMs) and potential prescribing omissions
(PPOs). One of the most common problems of inappropriate prescribing is gastro
intestinal track bleedings. For this purpose, nine of the 87 STOPP and START
criteria are designed to prevent this. However, the prevalence of gastro
intestinal track bleedings has not been established when these nine STOPP and
START criteria are violated. The database contained 182,000 patients belonging to
49 general practitioners in the region of Amsterdam, The Netherlands. We
estimated both the incidence of PIMs and PPOs and whether harm, in this case a
gastro-intestinal track bleeding, occurred. We found that although violation of
the nine STOPP or START criteria were possibly associated with harm (OR = 1.30),
this association was not statistically significant (p = 0.323). Searching for
evidence for harm informs decision support design aimed at improving quality of
medication prescription as it prioritizes the many suggested criteria based on
their relevance.
PMID- 28423858
TI - Needles in a Haystack: Screening and Healthcare System Evidence for Homelessness.
AB - Effectiveness of screening for homelessness in a large healthcare system was
evaluated in terms of successfully referring and connecting patients with
appropriate prevention or intervention services. Screening and healthcare
services data from nearly 6 million U.S. military veterans were analyzed.
Veterans either screened positive for current or risk of housing instability, or
negative for both. Current living situation was used to validate results of
screening. Administrative evidence for homelessness-related services was
significantly higher among positive-screen veterans who accepted a referral for
services compared to those who declined. Screening for current or risk of
homelessness led to earlier identification, which led to earlier and more
extensive service engagement.
PMID- 28423859
TI - Evidence for Busines Intelligence in Health Care: A Literature Review.
AB - This paper outlines a systematic literature review undertaken to establish
current evidence regarding the impact of Business Intelligence (BI) on health
system decision making and organizational performance. The review also examined
BI implementation factors contributing to these constructs. Following the
systematic review, inductive content analysis was used to categorize themes
within the eight articles identified. This study demonstrated there is little
evidence based literature focused on BI impact on organizational decision making
and performance within health care. There was evidence found that BI does improve
decision making. Implementation success was found to be dependent on several
factors, many of which relate to broader organizational culture and readiness.
PMID- 28423860
TI - Development of a Web-Based Quality Dashboard Including a Toolbox to Improve Pain
Management in Dutch Intensive Care.
AB - Audit and feedback (A&F) is a common strategy to improve quality of care. Meta
analyses have indicated that A&F may be more effective in realizing desired
change when baseline performance is low, it is delivered by a supervisor or
colleague, it is provided frequently and in a timely manner, it is delivered in
both verbal and written formats, and it includes specific targets and an action
plan. However, there is little information to guide operationalization of these
factors. Researchers have consequently called for A&F interventions featuring
well-described and carefully justified components, with their theoretical
rationale made explicit. This paper describes the rationale and development of a
quality dashboard including an improvement toolbox for four previous developed
pain indicators, guided by Control Theory.
PMID- 28423861
TI - A Digital Framework to Support Providers and Patients in Diabetes Related
Behavior Modification.
AB - We present Diabetes Web-Centric Information and Support Environment (D-WISE) that
features: (a) Decision support tool to assist family physicians to administer
Behavior Modification (BM) strategies to patients; and (b) Patient BM application
that offers BM strategies and motivational interventions to engage patients. We
take a knowledge management approach, using semantic web technologies, to model
the social cognition theory constructs, Canadian diabetes guidelines and BM
protocols used locally, in terms of a BM ontology that drives the BM decision
support to physicians and BM strategy adherence monitoring and messaging to
patients. We present the qualitative analysis of D-WISE usability by both
physicians and patients.
PMID- 28423864
TI - Adsorption of Uranyl Ions at the Nano-hydroxyapatite and Its Modification.
AB - Nano-hydroxyapatite and its modification, hydroxyapatite with the excess of
phosphorus (P-HAP) and hydroxyapatite with the carbon ions built into the
structure (C-HAP), were prepared by the wet method. They were studied by means of
XRD, accelerated surface area and porosimetry (ASAP), and SEM. The size of
crystallites computed using the Scherrer method was nano-hydroxyapatite (HAP) =
20 nm; P-HAP-impossible to determine; C-HAP = 22 nm; nano-HAP/U(VI) = 13.7 nm; P
HAP/U(VI)-impossible to determine, C-HAP/U(VI) = 11 nm. There were determined
basic parameters characterizing the double electrical layer at the nano
HAP/electrolyte and P-HAP/electrolyte, C-HAP/electrolyte inter faces: density of
the surface charge and zeta potential. The adsorption properties of nano-HAP
sorbent in relation to U(VI) ions were studied by the batch technique. The
adsorption processes were rapid in the first 60 min and reached the equilibrium
within approximately 120 min (for P-HAP) and 300 min (for C-HAP and nano-HAP).
The adsorption process fitted well with the pseudo-second-order kinetics. The
Freundlich, Langmuir-Freundlich, and Dubinin-Radushkevich models of isotherms
were examined for their ability to the equilibrium sorption data. The maximum
adsorption capabilities (q m ) were 7.75 g/g for P-HAP, 1.77 g/g for C-HAP, and
0.8 g/g for HAP at 293 K.
PMID- 28423865
TI - PEALD-Grown Crystalline AlN Films on Si (100) with Sharp Interface and Good
Uniformity.
AB - Aluminum nitride (AlN) thin films were deposited on Si (100) substrates by using
plasma-enhanced atomic layer deposition method (PEALD). Optimal PEALD parameters
for AlN deposition were investigated. Under saturated deposition conditions, the
clearly resolved fringes are observed from X-ray reflectivity (XRR) measurements,
showing the perfectly smooth interface between the AlN film and Si (100). It is
consistent with high-resolution image of the sharp interface analyzed by
transmission electron microscope (TEM). The highly uniform thickness throughout
the 2-inch size AlN film with blue covered surface was determined by
spectroscopic ellipsometry (SE). Grazing incident X-ray diffraction (GIXRD)
patterns indicate that the AlN films are polycrystalline with wurtzite structure
and have a tendency to form (002) preferential orientation with increasing of the
thickness. The obtained AlN films could open up a new approach of research in the
use of AlN as the template to support gallium nitride (GaN) growth on silicon
substrates.
PMID- 28423866
TI - Relaxation behavior of polyethylene welded joints.
AB - The paper presents results of the investigation of structure relaxation and
thermal properties of PE-80 and PE-100 polyethylene hot-tool butt welds. It was
found that a weld with the re-crystallized crystalline structure is formed during
the welding of dissimilar types of polyethylene. It is shown that within a long
period (1 year) the relaxation occurs not only in amorphous but also in the
crystalline phase (crystalline alpha-form transforms into mixed alphabeta-form),
with respective changes in polyethylene properties.
PMID- 28423867
TI - High Efficiency, Low Power-Consumption DFB Quantum Cascade Lasers Without Lateral
Regrowth.
AB - Very low power-consumption distributed feedback (DFB) quantum cascade lasers
(QCLs) at the wavelength around 4.9 MUm were fabricated by conventional process
without lateral regrowth of InP:Fe or using sidewall grating. Benefitted from the
optimized materials and low waveguide loss, very low threshold current density of
0.5 kA/cm2 was obtained for a device with cavity length of 2 mm. Combined with
the partial-high-reflection coating, the 1-mm-long DFB QCL achieved low power
consumption continuous wave (CW) operation up to 105 degrees C. The CW threshold
power-consumptions were 0.72 and 0.78 W at 15 and 25 degrees C, respectively.
The maximum CW output power was over 110 mW at 15 degrees C and still more than
35 mW at 105 degrees C. At 15 degrees C, wall-plug efficiency of 5.5% and slope
efficiency of 1.8 W/A were deduced, which were very high for low power
consumption DFB QCLs.
PMID- 28423868
TI - Genetic parameters of calving ease using sire-maternal grandsire model in Korean
Holsteins.
AB - OBJECTIVE: Calving ease (CE) is a complex reproductive trait of economic
importance in dairy cattle. This study was aimed to investigate the genetic
merits of CE for Holsteins in Korea. METHODS: A total of 297,614 field records of
CE, from 2000 to 2015, from first parity Holstein heifers were recorded
initially. After necessary data pruning such as age at first calving (18 to 42
mo), gestation length, and presence of sire information, final datasets for CE
consisted of 147,526 and 132,080 records for service sire calving ease (SCE) and
daughter calving ease (DCE) evaluations, respectively. The CE categories were
ordered and scores ranged from CE1 to CE5 (CE1, easy; CE2, slight assistance;
CE3, moderate assistance; CE4, difficult calving; CE5, extreme difficulty
calving). A linear transformation of CE score was obtained on each category using
Snell procedure, and a scaling factor was applied to attain the spread between 0
(CE5) and 100% (CE1). A sire-maternal grandsire model analysis was performed
using ASREML 3.0 software package. RESULTS: The estimated direct heritability
(h2) from SCE and DCE evaluations were 0.11+/-0.01 and 0.08+/-0.01, respectively.
Maternal h2 estimates were 0.05+/-0.02 and 0.04+/-0.01 from SCE and DCE
approaches, respectively. Estimates of genetic correlations between direct and
maternal genetic components were -0.68+/-0.09 (SCE) and -0.71+/-0.09 (DCE). The
average direct genetic effect increased over time, whereas average maternal
effect was low and consistent. The estimated direct predicted transmitting
ability (PTA) was desirable and increasing over time, but the maternal PTA was
undesirable and decreasing. CONCLUSION: The evidence on sufficient genetic
variances in this study could reflect a possible selection improvement over time
regarding ease of calving. It is expected that the estimated genetic parameters
could be a valuable resource to formulate sire selection and breeding plans which
would be directed towards the reduction of calving difficulty in Korean
Holsteins.
PMID- 28423869
TI - Protective effects of Bacillus subtilis against Salmonella infection in the
microbiome of Hy-Line Brown layers.
AB - OBJECTIVE: This study investigated the effects of Bacillus subtilis CSL2 (B.
subtilis CSL2) administration before Salmonella challenge on the fecal microbiota
and microbial functionality of Hy-line Brown (HLB) laying hens. METHODS: Fecal
samples were collected from control (CON), Salmonella-infected (SAL) and
Salmonella-infected, probiotic-treated (PRO) groups before and after Salmonella
challenge for microbiome analysis using 16S rRNA gene pyrosequencing. RESULTS:
Infection with Salmonella led to decreased microbial diversity in hen feces;
diversity was recovered with Bacillus administration. In addition, Salmonella
infection triggered significant alterations in the composition of the fecal
microbiota. The abundance of the phylum Firmicutes decreased while that of
Proteobacteria, which includes a wide variety of pathogens, increased
significantly. Bacillus administration resulted in normal levels of abundance of
Firmicutes and Proteobacteria. Analysis of bacterial genera showed that
Salmonella challenge decreased the population of Lactobacillus, the most abundant
genus, and increased populations of Pseudomonas and Flavobacterium genera by a
factor of 3 to 5. On the other hand, Bacillus administration caused the abundance
of the Lactobacillus genus to recover to control levels and decreased the
population of Pseudomonas significantly. Further analysis of operational
taxonomic units revealed a high abundance of genes associated with two-component
systems and secretion systems in the SAL group, whereas the PRO group had more
genes associated with ribosomes. CONCLUSION: The results of this study indicate
that B. subtilis CSL2 administration can modulate the microbiota in HLB laying
hens, potentially acting as a probiotic to protect against Salmonella Gallinarum
infection.
PMID- 28423870
TI - Effects of physically effective neutral detergent fiber content on dry matter
intake, digestibility, and chewing activity in Korean native goats (Capra hircus
coreanae) fed with total mixed ration.
AB - OBJECTIVE: This experiment was to determine proper physical traits in the diet
for goats by investigating the effects of physically effective neutral detergent
fiber (peNDF) content on dry matter intake (DMI), digestibility, and chewing
activity in black goats fed with total mixed ration (TMR). METHODS: Six growing
wethers of Korean native black goats (Capra hircus coreanae) aged 8 months and
weighing between 26.9 kg and 27.1 kg (27.03+/-5.05 kg) were used in this
experiment. Three diets of varying peNDF content were obtained by original TMR
(T1), 12,000 rpm grinding (T2), and 15,500 rpm grinding (T3) of the same TMR
diet. The peNDF1.18 content of the experimental diets was 23.85%, 21.71%, and
16.22% for T1, T2, and T3, respectively. RESULTS: Average daily gain (ADG) was
higher in T2 group compared to those of the control and T3 groups, but ADG and
DMI were not affected by the dietary particle size and peNDF content. Also, there
was no difference between apparent nutrient digestibility of dry matter, crude
fiber, ether extract, neutral detergent fiber, and acid detergent fiber. Although
there was no significant difference, rumination and total chewing time were
associated with decreased peNDF content. CONCLUSION: The feeding of peNDF-based
TMR showed no impact on apparent nutrient digestibility and nitrogen balance.
Further studies are required with a wider range of dietary peNDF level and
particle size to better identify the effect of dietary peNDF and particle size on
chewing activity and performance in goats.
PMID- 28423871
TI - Behavioral characteristics of Hanwoo (Bos taurus coreanae) steers at different
growth stages and seasons.
AB - OBJECTIVE: This research analyzed behavioral characteristics of Hanwoo (Bos
taurus coreanae) steers during each season and growth stage to enable measurement
of the animals' welfare level for precision livestock farming. METHODS: A hundred
eight beef steers were divided into three equal groups at a Hanwoo farm according
to their growth stage: growing stage (GS), 8 months; early-fattening stage (EFS),
19 months; and late-fattening stage (LFS), 30 months. Twelve behavioral
categories were continuously recorded for 13 day-time hours in each four seasons
with three replications. RESULTS: Time spent standing was found to be
significantly longer in summer at all growth stages (p<0.05). Hanwoos at the GS
spent significantly longer standing time in spring and summer than those at the
EFS and LFS (p<0.05). Lying time in summer was the shortest for all growth stages
(p<0.05). Steers at the LFS spent significantly longer lying time than that at
the GS (p<0.05) in summer. For GS and EFS, time spent eating in spring and autumn
were longer than in summer and winter (p<0.05). Eating time was the longest for
the GS in spring, autumn, and winter, excluding for the LFS in winter (p<0.05).
Regarding ruminating, steers at the LFS spent significantly shorter time than
those at other stages in all seasons (p<0.05). GS and EFS steers showed the
longest walking time in summer compared with other seasons (p<0.05). At GS and
LFS, drinking time in summer was the longest of all seasons (p<0.05). Sleeping
time was significantly shorter in summer compared with the other seasons
(p<0.05). Self-grooming time was the longest in winter for all growth stages
(p<0.05). CONCLUSION: Steers were found to have more variable behavioral patterns
during summer and the GS and less active behaviors during the LFS, thus extra
care seems necessary during the GS, LFS, and summer period.
PMID- 28423872
TI - Potential antioxidant and lipid peroxidation inhibition of Phyllanthus acidus
leaf extract in minced pork.
AB - OBJECTIVE: This study investigated the effect of extraction solvents on
antioxidant bio-active compounds as well as potential antioxidant and lipid
peroxidation inhibition of Phyllanthus acidus (P. acidus) leaf extract in minced
pork. METHODS: The effect of various solvent systems of water, 25%, 50%, 75%
(v/v) ethanol in water and absolute ethanol on the extraction crude yield, total
phenolic content, total flavonoid content and in vitro antioxidant activities of
P. acidus leaves was determined. In addition, antioxidant activities of the
addition of crude extract from P. aciuds leaves at 2.5 and 5 g/kg in minced pork
on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2'-Azino-bis(3
ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation
decolorization, reducing power and inhibition of lipid peroxidation
(thiobarbituric acid reactive substances; TBARS) were determined. Moreover,
sensory evaluation of the samples was undertaken by using a 7-point hedonic
scale. RESULTS: The results showed that the highest crude yield (2.8 g/100 g dry
weight) was obtained from water which also had the highest recovery yield for
total phenolic content, total flavonoid content and the strongest antioxidant
activity. The addition of crude water extract from P. acidus leaves was more
effective in retarding lipid peroxidation and higher antioxidant activity than
control and butylated hydroxytoluene in minced pork. In particular, the samples
containing P. acidus extract had no significant effect on the sensory scores of
overall appearance, color, odor, texture, flavor, and overall acceptability
compared to the control. CONCLUSION: Water solvent was an optimally appropriate
solvent for P. acidus leaf extraction because of its ability to yield the highest
amount of bio-active compounds and in vitro antioxidant property. Particularly,
P. acidus crude water extract also strongly expressed the capacity to retard
lipid oxidation, radical scavenging, radical cation decolorization and reducing
power in minced pork. The results of this study indicated that P. acidus leaf
extract could be used as natural antioxidant in the pork industry.
PMID- 28423873
TI - Replacing groundnut cake with gluten meals of rice and maize in diets for growing
Sahiwal cattle.
AB - OBJECTIVE: This experiment investigated the effect of isonitrogenous replacement
of groundnut cake (GNC) by rice gluten meal (RGM) and maize gluten meal (MGM) at
75% level on nutrient intake, apparent digestibility, growth performance and
related blood constituents in growing Sahiwal cattle. METHODS: Eighteen Sahiwal
calves were divided into three groups, based on average body weight (87.24 kg)
and age (6 to 12 mo), and treatments were assigned to the different groups
randomly. The first group (GP-I) was kept as control and received GNC-based
concentrate mixture. In second (GP-II) and third (GP-III) groups, 750 g/kg
nitrogen (N) of GNC was substituted by RGM and MGM respectively, with similar
forage:concentrate ratio (56:44). RESULTS: The 90 days of experimental feeding
revealed that intake of dry matter, crude protein and digestibility coefficients
for all nutrients did not differ among groups. Furthermore, although N balance
was greater (p<=0.05) for GP-III than GP-I and GP-II, average daily gain was
similar between GP-I and GP-II but greater (p<=0.05) for GP-III. In addition,
feed efficiency and related haematological variables did not differ due to
treatments. CONCLUSION: Nutritional worth of GNC and RGM was highly comparable in
terms of intake, digestibility and growth in growing calves. However, MGM was
found to be more efficacious in improving growth rate than RGM at 75% replacement
level of GNC protein.
PMID- 28423874
TI - The relationship between the variants in the 5'-untranslated regions of equine
chorionic gonadotropin genes and serum equine chorionic gonadotropin levels.
AB - OBJECTIVE: An experiment was conducted to study the association between the
single nucleotide polymorphisms (SNPs) in 5'-untranslated regions (5'-UTR) of
equine chorionic gonadotropin (eCG) genes and the serum eCG levels. METHODS: SNPs
in 5'-UTR of eCG genes were screened across 10 horse breeds, including 7 Chinese
indigenous breeds and 3 imported breeds using iPLEX chemistry, and the
association between the serum eCG levels of 174 pregnant Da'an mares and their
serum eCG levels (determined with ELISA) was analyzed. RESULTS: Four SNPs were
identified in the 5'-UTR of the eCGalpha gene, and one of them was unique in the
indigenous breeds. There were 2 SNPs detected at the 5' end of the eCGbeta
subunit gene, and one of them was only found in the Chinese breeds. The SNP
g.39948246T>C at the 5'-UTR of eCGalpha was associated significantly with eCG
levels of 75-day pregnant mare serum (p<0.05) in Da'an mares. Prediction analysis
on binding sites of transcription factors showed that the g.39948246T>C mutation
causes appearance of the specific binding site of hepatocyte nuclear factor 3
forkhead homolog 2 (HFH-2), which is a transcriptional repressor belonging to the
forkhead protein family of transcription factors. CONCLUSION: The SNP
g.39948246T>C at the 5'-UTR of eCGalpha is associated with eCG levels of 75-day
pregnant mare serum (p<0.05).
PMID- 28423875
TI - Adaptive selection at agouti gene inferred breed specific selection signature
within the indigenous goat populations.
AB - Objective: The aim of this study was to calculate selection signatures at
possible loci leading to population differentiation, as well as pattern of
selection of agouti gene within the local goat breeds and its correlation among
other animal species to reveal molecular evolution. Methods: The high Fst outlier
method corresponding to Fst distribution was used to identify the loci subject to
positive selection. According to the empirical distribution of Fst estimates, we
selected the SNPs having high Fst outlier corresponded to the upper 1% of the
distribution as the loci under selection. In five goat populations 14 SNPs were
determined from 14 genes to be subjected to natural or artificial selection. The
selective pressures were measured with the non-synonymous to synonymous
substitution rate ratio omega (dN/dS), where omega=1, omega<1 and omega>1
correspond to neutral, purifying and positive selection, respectively. Results:
The loci were analyzed for positive selection and the most locus undergone
positive selection was Agouti-2. Positive selection of agouti gene was analyzed
with FDIST analysis using outlier approach, agouti gene showed a significant
positive selection in the outlier area as there was a strong evidence of positive
selection for this locus because of its low heterozygosity. Analysis showed that
previously agouti gene was initially under purified selection, but now is under
adaptive positive selection. The data was explored by two sets of nested models
(M1-M2; M7-M8) and LRT was concluded by using likelihood estimates. The
nucleotide sequence of goat agouti gene showed closer coding sequence similarity
to agouti gene of sheep (99.3%), buffalo (98.3%) cattle (98%), and wild yak
(95.3%) and human (85.5%). Conclusion: This study provides strong evidence of
breed specific selection of the agouti gene within the indigenous goat breeds. We
also demonstrate comprehensive approaches formulating systemic searches for
genes; that have undergone positive selection in lineages.
PMID- 28423876
TI - Effects of confinement on physiological and psychological responses and
expression of interleukin 6 and brain derived neurotrophic factor mRNA in
primiparous and multiparous weaning sows.
AB - OBJECTIVE: The present study aimed to investigate whether the long-lasting,
recurrent restricting of sows leads to the physiological and psychological
reaction of discomfort. METHODS: Sows (Large White) that had experienced
restricting for about 0.5 or 3 years and age-matched sows kept in a group housing
system (loose sows) were compared. Pupillary light reflex parameters were
measured at the weaning stage. Immediately after slaughter, blood samples were
taken to measure serum cortisol levels, and the brain was dissected, gene
expression in the hippocampus, frontal cortex and hypothalamus was analyzed.
RESULTS: The serum cortisol levels were higher in the confined sows than in the
loose sows. The full maturity, but not the young adolescent, confined sows had
longer latency time in the onset of pupil constriction than their loose
counterparts. Real-time polymerase chain reaction analyses revealed an increased
expression of interleukin 6 mRNA in the hippocampus and decreased expression of
brain derived neurotrophic factor mRNA in hippocampus and hypothalamus and to a
lesser extent in the frontal cortex of the full maturity confined sows, compared
with the full maturity loose sows. CONCLUSION: Taken together, these data
indicated that recurrent restricting stress in full maturity sows leads to the
physiological and psychological reaction of discomfort.
PMID- 28423877
TI - Identification of Polymorphisms and Association of Five KAP Genes with Sheep Wool
Traits.
AB - Objective: The objective of this study was to detect and evaluate the
associations of possible polymorphisms of six exon regions within five KAP genes
(KAP6.1, KAP8.1, KAP8.2, KRTAP9-2 and KAP16.4 [KAP16.4-1 and KAP16.4-2]) with
wool traits in 418 Chinese Merino (Xinjiang type) (CMXT) sheep. Methods: The PCR
SSCP (polymerase chain reaction-based single-strand conformation polymorphism),
DNA sequencing, and the gene pyramiding effect methods were used to detect the
polymorthisms and the association analysis. Results: We detected 21 mutation loci
(single-nucleotide polymorphisms) within the five KAP genes. Of these loci, three
(EX_33-35insA, EX_45-47insA, and EX_61-63insT) were indel mutations, four
mutation loci (EX_54-56delA, EX_52-54delC, EX_45-47delA, and EX_34-36delA) were
deletion mutations, and 14 (EX_C35A, EX_G132C, EX_C54T, EX_G162A, EX_C166A,
EX_A167T, EX_C85A, EX_A133C, EX_G89A, EX_G137A, EX_G188A, EX_A190C, EX_A196T, and
EX_G78C) were silent mutations. Association analysis indicated that different
genotypes of six primer (P1-P6) fragments were significantly associated with
traits, (P < 0.05) in CMXT sheep. Analysis of the gene pyramiding effect between
the different genotypes of the gene sites KAP6.1 and KRTAP9-2, KAP8.1 and KAP8.2,
and KAP16.4-1 and KAP16.4-2, each genotype in a gene site was combined with all
the genotypes of another gene site and formed the different combined genotypes in
each pair of combined site, indicated a total of 36 types of possible combined
genotypes in the analyzed population. Compared with the other combined genotypes,
the combinations AAEE, GGII, and KKNN at gene sites KAP6.1-KRTAP9-2, KAP8.1
KAP8.2, and KAP16.4-1-KAP16.4-2, respectively, had a greater effect on wool
traits (P < 0.05). Conclusion: Our results indicate that the single-nucleotide
polymorphisms and combined genotypes have a significant effect on the wool traits
of CMXT individuals, and could be used as candidate markers for sheep wool traits
in sheep breeding programs.
PMID- 28423878
TI - Effects of alfalfa flavonoids on the production performance, immune system, and
ruminal fermentation of dairy cows.
AB - OBJECTIVE: The objective of this study was to examine the effects of alfalfa
flavonoids on the production performance, immunity, and ruminal fermentation of
dairy cows. METHODS: The experiments employed four primiparous Holstein cows
fitted with ruminal cannulas, and used a 4*4 Latin square design. Cattle were fed
total mixed ration supplemented with 0 (control group, Con), 20, 60, or 100 mg of
alfalfa flavonoids extract (AFE) per kg of dairy cow body weight (BW). RESULTS:
The feed intake of the group receiving 60 mg/kg BW of AFE were significantly
higher (p<0.05) than that of the group receiving 100 mg/kg BW. Milk yields and
the fat, protein and lactose of milk were unaffected by AFE, while the total
solids content of milk reduced (p = 0.05) linearly as AFE supplementation was
increased. The somatic cell count of milk in group receiving 60 mg/kg BW of AFE
was significantly lower (p<0.05) than that of the control group. Apparent total
tract digestibility of neutral detergent fiber and crude protein showed a
tendency to increase (0.050.05), but changes in bacterial composition were
found. CONCLUSION: From the present study, it is inferred that EW is beneficial
for rumen fermentation, and weaning when the feed intake of the starter reached
750 g showed much better results.
PMID- 28423880
TI - Effects of vertebral number variations on carcass traits and genotyping of
Vertnin candidate gene in Kazakh sheep.
AB - OBJECTIVE: The vertebral number is associated with body length and carcass
traits, which represents an economically important trait in farm animals. The
variation of vertebral number has been observed in a few mammalian species.
However, the variation of vertebral number and quantitative trait loci in sheep
breeds have not been well addressed. METHODS: In our investigation, the
information including gender, age, carcass weight, carcass length and the number
of thoracic and lumbar vertebrae from 624 China Kazakh sheep was collected. The
effect of vertebral number variation on carcass weight and carcass length was
estimated by general linear model. Further, the polymorphic sites of Vertnin
(VRTN) gene were identified by sequencing, and the association of the genotype
and vertebral number variation was analyzed by the one-way analysis of variance
model. RESULTS: The variation of thoracolumbar vertebrae number in Kazakh sheep
(18 to 20) was smaller than that in Texel sheep (17 to 21). The individuals with
19 thoracolumbar vertebrae (T13L6) were dominant in Kazakh sheep (79.2%). The
association study showed that the numbers of thoracolumbar vertebrae were
positively correlated with the carcass length and carcass weight, statistically
significant with carcass length. To investigate the association of thoracolumbar
vertebrae number with VRTN gene, we genotyped the VRTN gene. A total of 9
polymorphic sites were detected and only a single nucleotide polymorphism (SNP)
(rs426367238) was suggested to associate with thoracic vertebral number
statistically. CONCLUSION: The variation of thoracolumbar vertebrae number
positively associated with the carcass length and carcass weight, especially with
the carcass length. VRTN gene polymorphism of the SNP (rs426367238) with
significant effect on thoracic vertebral number could be as a candidate marker to
further evaluate its role in influence of thoracolumbar vertebral number.
PMID- 28423881
TI - Effects of calcium propionate on the fermentation quality and aerobic stability
of alfalfa silage.
AB - OBJECTIVE: To assess the potency of calcium propionate (CAP) used as silage
additive, an experiment was carried out to evaluate the effect of CAP on the
nitrogen transformation, fermentation quality and aerobic stability of alfalfa
silages. METHODS: Alfalfa was ensiled with four levels of CAP (5, 10, 15, and 20
g/kg of fresh weight [FW]) in laboratory silos for 30 days. After opening, the
silages were analyzed for the chemical and microbiological characteristics, and
subjected to an aerobic stability test. RESULTS: The increasing proportion of CAP
did not affect pH, lactic acid (LA) concentrations and yeast counts, while
linearly decreased counts of enterobacteria (p = 0.029), molds (p<0.001) and
clostridia (p<0.001), and concentrations of acetic acid (p<0.001), propionic acid
(p<0.001), butyric acid (p<0.001), and ethanol (p = 0.007), and quadratically (p
= 0.001) increased lactic acid bacteria counts. With increasing the proportion of
CAP, the dry matter (DM) loss (p<0.001), free amino acid N (p<0.001), ammonia N
(p = 0.004), and non-protein N (p<0.001) contents were linearly reduced, whereas
DM (p = 0.048), water soluble carbohydrate (p<0.001) and peptide N (p<0.001)
contents were linearly increased. The highest Flieg's point was found in CAP10
(75.9), represented the best fermentation quality. All silages treated with CAP
improved aerobic stability as indicated by increased stable hours compared with
control. CONCLUSION: The addition of CAP can suppress the undesirable
microorganisms during ensiling and exposure to air, thereby improving the
fermentation quality and aerobic stability as well as retarding the proteolysis
of alfalfa silage. It is suggested that CAP used as an additive is recommended at
a level of 10 g/kg FW.
PMID- 28423882
TI - Various levels of rapeseed meal in weaning pig diets from weaning to finishing
periods.
AB - OBJECTIVE: This experiment was conducted to investigate the influence of rapeseed
meal (RSM) supplementation in weaning pig diet on growth performance, blood
profile, carcass characteristics and economic analysis on weaning to finishing
pigs. METHODS: A total of 120 cross bred ([Yorkshire*Landrace]*Duroc) weaning
pigs were allotted to 5 treatments in a randomized complete block design. Each
treatment had 4 replications with 6 pigs per pen. Five different levels of RSM
(0%, 2%, 4%, 6%, and 8%) were used as dietary treatments. RESULTS: Overall, no
treatment showed significant differences in growth performance with increased
dietary RSM levels. The concentration of blood urea nitrogen (BUN) decreased as
dietary RSM levels increased in 6 weeks (linear response, p<0.01). Total
cholesterol, high density lipoprotein cholesterol, low density lipoprotein
cholesterol, triiodothyronine, and thyroxine showed no significant differences,
neither were there any significant differences in the immune response (IgG and
IgA). As the dietary RSM levels of weaning pig diet were increased, no
differences were found among dietary treatments upon performing proximate
analyses of the pork after finishing. The influence of RSM supplementation on
nutrient digestibility and nitrogen retention were not affected by dietary RSM
levels either. With increased dietary RSM levels in the weaning pig diet, no
differences among dietary treatments were found after performing proximate
analyses of the pork's physiochemical properties. In addition, there were no
significant differences observed in pork colors, pH levels, and economic
benefits. CONCLUSION: Consequently, this experiment demonstrated that weaning
pig's diet containing RSM influenced BUN concentration, but there were no
detrimental effects on the growth performance of weaning pigs with up to 8% RSM
in the diet.
PMID- 28423883
TI - Comparison of growth performance of Berkshire purebreds and crossbreds sired by
Hereford and Tamworth breeds raised in alternative production system.
AB - OBJECTIVE: The objective of the present study was to compare growth performance
of Berkshire purebred pigs (BB), Hereford (HB) and/or Tamworth (TB) sired
Berkshire crossbred pigs reared in a hoop structure in two experiments. METHODS:
In the first experiment, BB was compared to TB while HB and TB were compared in
the second. Body weights (BW) were recorded at 3 days of age and every 28 days
from birth until 140 days of age. There was no significant difference between the
BW of BB and TB, but HB was heavier than TB by 84 days of age. Least square means
of average daily gain (ADG) were evaluated using one-way analysis of variance.
RESULTS: The mean parity (+/-standard deviation) of the sows was 3.42+/-2.14 and
a total of 45 farrowing occurred from year 2012 to 2014. The mean number of total
born, number born alive, number of mummies, and number weaned were 9.23+/-2.52,
7.87+/-2.53, 0.04+/-0.21, and 5.94+/-2.74, respectively. Parity did not have a
significant effect on the growth performance of the pigs. For BB and TB, there
was only one time frame in which there was a significant difference in the ADG:
between 28 and 56 days of age. For HB and TB, the overall ADG of HB was
significantly greater than the total ADG of TB. CONCLUSION: The breed of the sire
did not affect the growth performance of the progeny between Berkshire purebreds
and Tamworth*Berkshire crossbreds. The breed of the sire did have an effect
between Hereford and Tamworth sired Berkshire crossbreds (p<0.05). The Hereford
sired pigs were found to have increased growth performance compared to Tamworth
sired.
PMID- 28423884
TI - Integrating market chain assessments with zoonoses risk analysis in two cross
border pig value chains in Lao PDR.
AB - OBJECTIVE: Lao PDR's recent accession to the World Trade Organization
necessitates a greater understanding of the patterns and risk of livestock
production in order to better align national policy with the Agreement on the
Application of Sanitary and Phytosanitary Measures. This eco-health study was
conducted to improve understanding of the interrelations between market chains
and zoonotic infection risks at two strategic cross border points between Lao
PDR, Thailand and Viet Nam. METHODS: Information gained from smallholder
farmer/trader interviews was integrated with serological surveys for pig
associated zoonoses-including hepatitis E virus (HEV), Taenia solium (T. solium)
and trichinella-to identify potential linkages between disease risk and pig
production and slaughter in low input systems common across the country. RESULTS:
Trichinella and HEV exposure was high in both humans and pigs in both study
areas, significantly associated with pig slaughter and the subsequent consumption
and handling of raw pork products. T. solium demonstrated a strong geographical
and ethnic association with the northern study area bordering Vietnam. With the
right knowledge and accessible, affordable inputs, the majority of smallholder
farmers indicated a willingness to invest more in pig production, which could
simultaneously improve livelihoods and decrease exposure to HEV, Trichinella, and
T. solium through increased access to formal markets and an improved slaughter
processes. CONCLUSION: The linkages identified when assessing disease risk in the
context of potential economic and cultural drivers of transmission highlight the
importance of a systems-based approach for the detection and control of zoonotic
disease, and contributes to an improved understanding of the Lao PDR livestock
sector.
PMID- 28423885
TI - Effect of fermented biogas residue on growth performance, serum biochemical
parameters, and meat quality in pigs.
AB - OBJECTIVE: This study investigated the effect of fermented biogas residue (FBR)
of wheat on the performance, serum biochemical parameters, and meat quality in
pigs. METHODS: We selected 128 pigs (the mean initial body weight was 40.24+/
3.08 kg) and randomly allocated them to 4 groups (1 control group and 3 treatment
groups) with 4 replicates per group and 8 pigs per pen in a randomized complete
block design based on initial body weight and sex. The control group received a
corn-soybean meal-based diet, the treatment group fed diets containing 5%, 10%,
and 15% FBR, respectively (abbreviated as FBR5, FBR10, and FBR15, respectively).
Every group received equivalent-energy and nitrogen diets. The test lasted 60
days and was divided into early and late stages. Blood and carcass samples were
obtained on 60 d. Meat quality was collected from two pigs per pen. RESULTS:
During the late stage, the average daily feed intake and average daily gain of
the treatment groups was greater than that of the control group (p<0.05). During
the entire experiment, the average daily gain of the treatment groups was higher
than that of the control group (p<0.05). Fermented biomass residue did not
significantly affect serum biochemical parameters or meat quality, but did affect
amino acid profiles in pork. The contents of Asp, Arg, Tyr, Phe, Leu, Thr, Ser,
Lys, Pro, Ala, essential amino acids, non-essential amino acids, and total amino
acids in pork of FBR5 and FBR10 were greater than those of the control group
(p<0.05). CONCLUSION: These combined results suggest that feeding FBR could
increase the average daily gain and average daily feed intake in pigs and the
content of several flavor-promoting amino acids.
PMID- 28423886
TI - Adiponectin induced AMP-activated protein kinase impairment mediates insulin
resistance in Bama mini-pig fed high-fat and high-sucrose diet.
AB - OBJECTIVE: Adipose tissue is no longer considered as an inert storage organ for
lipid, but instead is thought to play an active role in regulating insulin
effects via secretion adipokines. However, conflicting reports have emerged
regarding the effects of adipokines. In this study, we investigated the role of
adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs.
METHODS: An obesity model was established in Bama mini-pigs, by feeding with high
fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry
levels were measured, and intravenous glucose tolerance test was performed.
Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor
necrosis factor alpha (TNF-alpha), and glucose-induced insulin secretion were
also examined by radioimmunoassay. AMP-activated protein kinase (AMPK)
phosphorylation in skeletal muscle, which is a useful insulin resistance marker,
was examined by immunoblotting. Additionally, associations of AMPK
phosphorylation with plasma adipokines and homeostasis model assessment of
insulin resistance (HOMA-IR) index were assessed by Pearce's correlation
analysis. RESULTS: Obese pigs showed hyperglycemia, high triglycerides, and
insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and
IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and
adipose tissue, corroborating data from obese mice and humans. However,
circulating resistin and TNF-alpha showed no difference, while the values of TNF
alpha in adipose tissue were significantly higher in obese pigs, also in
agreement with data from obese humans but not rodent models. Moreover, strong
associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and
HOMA-IR index were obtained. CONCLUSION: AMPK impairment induced by adiponectin
decrease mediates insulin resistance in high-fat and high-sucrose diet induction.
In addition, Bama mini-pig has the possibility of a conformable model for human
metabolic diseases.
PMID- 28423887
TI - The effect of lactation number, stage, length, and milking frequency on milk
yield in Korean Holstein dairy cows using automatic milking system.
AB - OBJECTIVE: The aim of the current study was to describe the relationship between
milk yield and lactation number, stage, length and milking frequency in Korean
Holstein dairy cows using an automatic milking system (AMS). METHODS: The
original data set consisted of observations from April to October 2016 of 780
Holstein cows, with a total of 10,751 milkings. Each time a cow was milked by an
AMS during the 24 h, the AMS management system recorded identification numbers of
the AMS unit, the cow being milking, date and time of the milking, and milk yield
(kg) as measured by the milk meters installed on each AMS unit, date and time of
the lactation, lactation stage, milking frequency (NoM). Lactation stage is
defined as the number of days milking per cows per lactation. Milk yield was
calculated per udder quarter in the AMS and was added to 1 record per cow and
trait for each milking. Milking frequency was measured the number of milkings per
cow per 24 hour. RESULTS: From the study results, a significant relationship was
found between the milk yield and lactation number (p<0.001), with the maximum
milk yield occurring in the third lactation cows. We recorded the highest milk
yield, in a greater lactation length period of early stage (55 to 90 days) at a
4* milking frequency/d, and the lowest milk yield was observed in the later stage
(>201 days) of cows. Also, milking frequency had a significant influence on milk
yield (p<0.001) in Korean Holstein cows using AMS. CONCLUSION: Detailed knowledge
of these factors such as lactation number, stage, length, and milking frequency
associated with increasing milk yield using AMS will help guide future
recommendations to producers for maximizing milk yield in Korean Dairy
industries.
PMID- 28423888
TI - Effects of two litter amendments on air NH3 levels in broiler closed-houses.
AB - OBJECTIVE: High NH3 emissions from poultry houses are reported to have negative
impacts on health, welfare and safety of birds and humans, and on the
environment. Objective of the present study was to determine the effects of two
litter amendments on the NH3 levels in broiler closed houses under hot-humid
conditions. METHODS: Giving a completely randomize design, nine closed houses,
each housed 32,500 birds on paddy husk litter, were randomly allocated into two
treatment (Mizuho; a bacterial culture mix and Rydall OE; an enzymatic
biocatalyst) and control groups. NH3 levels were determined thrice a day (0600,
1200, and 1800 h), at three heights from the litter surface (30, 90, and 150 cm),
at 20 predetermined locations of a house, from day 1 to 41. RESULTS: Rydall
significantly reduced the NH3 level compared to control and Mizuho. NH3 levels at
30 cm were significantly higher than that of 90 and 150 cm. The NH3 levels at 30
cm height were higher than 25 ppm level from day 9, 11, and 13 in Mizuho,
control, and Rydall groups, respectively to day 41. NH3 levels at 150 cm height
were higher than maximum threshold limit of 50 ppm for human exposure from day
12, 14, and 15 in Mizuho, control, and Rydall groups, respectively to day 33.
Being significantly different among each other, the NH3 level was highest and
lowest at 0600 and 1800 h. Litter amendments had no significant effects on growth
performance. Rydall significantly increased the litter N content on day 24.
CONCLUSION: It was concluded that the NH3 levels of closed house broiler
production facilities under tropical condition are so high that both birds and
workers are exposed to above recommended levels during many days of the growing
period. Compared to microbial culture, the enzymatic biocatalyst was found to be
more effective in reducing NH3 level.
PMID- 28423889
TI - WITHDRAWN:Polymorphism Of Bola-DRB3 gene and its association with embryo
development after in vitro fertilization in Slovak spotted x Holstein-Fresian
crossbred cattle.
AB - Ahead of Print article withdrawn by publisher.
PMID- 28423890
TI - Physicochemical characteristics and fatty acid profiles of muscle tissues from
Hanwoo steers fed a total mixed ration supplied with medicinal plant by-products.
AB - OBJECTIVE: Using medicinal plant by-products (MPBP) as feed additives may be an
eco-friendly option as substitutes for feedstuffs and may assist in reducing the
improper disposal of MPBP. Therefore, this study was conducted to evaluate the
influences of MPBP on the meat quality of Hanwoo steers fed a total mixed ration
(TMR). METHODS: Twenty seven steers (body weight = 573+/-57 kg) were randomly
divided into three treatments with a control group and two tested groups as
follows: control, 1,000 g/kg TMR; treatment 1 (MPBP30), 970 g/kg TMR and 30 g/kg
MPBP; treatment 2 (MPBP50), 950 g/kg TMR and 50 g/kg MPBP. RESULTS: Average daily
gain, feed conversion ratio and the Commission Internationale de l'Eclairage L*
of muscle were improved (p<0.05, respectively) by MPBP30. Stearic acid (C18:0)
was decreased (linear effect, p = 0.012), while oleic acid (C18:1) was increased
(linear effect, p = 0.055) by MPBP level. Saturated fatty acid (SFA) and
polyunsaturated fatty acid (PUFA) were decreased for MPBP50 while unsaturated
fatty acid (USFA) and monounsaturated fatty acid (MUFA) were increased for MPBP
50. USFA and SFA ratio was increased for MPBP50 as well. CONCLUSION: These
results indicated that MPBP supplementation in Hanwoo steers fed a TMR increased
feed efficiency and meat color (lightness) with altering fatty acid proportions.
Therefore, MPBP may be successfully used in ruminant feeding.
PMID- 28423891
TI - Effective Thermal Inactivation of the Spores of Bacillus cereus Biofilms Using
Microwave.
AB - Microwave sterilization was performed to inactivate the spores of biofilms of
Bacillus cereus involved in foodborne illness. The sterilization conditions, such
as the amount of water and the operating temperature and treatment time, were
optimized using statistical analysis based on 15 runs of experimental results
designed by the Box-Behnken method. Statistical analysis showed that the optimal
conditions for the inactivation of B. cereus biofilms were 14 ml of water, 108
degrees C of temperature, and 15 min of treatment time. Interestingly, response
surface plots showed that the amount of water is the most important factor for
microwave sterilization under the present conditions. Complete inactivation by
microwaves was achieved in 5 min, and the inactivation efficiency by microwave
was obviously higher than that by conventional steam autoclave. Finally, confocal
laser scanning microscopy images showed that the principal effect of microwave
treatment was cell membrane disruption. Thus, this study can contribute to the
development of a process to control food-associated pathogens.
PMID- 28423892
TI - O2 Plasma Etching and Antistatic Gun Surface Modifications for CNT Yarn
Microelectrode Improve Sensitivity and Antifouling Properties.
AB - Carbon nanotube (CNT) based microelectrodes exhibit rapid and selective detection
of neurotransmitters. While different fabrication strategies and geometries of
CNT microelectrodes have been characterized, relatively little research has
investigated ways to selectively enhance their electrochemical properties. In
this work, we introduce two simple, reproducible, low-cost, and efficient surface
modification methods for carbon nanotube yarn microelectrodes (CNTYMEs): O2
plasma etching and antistatic gun treatment. O2 plasma etching was performed by a
microwave plasma system with oxygen gas flow and the optimized time for treatment
was 1 min. The antistatic gun treatment flows ions by the electrode surface; two
triggers of the antistatic gun was the optimized number on the CNTYME surface.
Current for dopamine at CNTYMEs increased 3-fold after O2 plasma etching and 4
fold after antistatic gun treatment. When the two treatments were combined, the
current increased 12-fold, showing the two effects are due to independent
mechanisms that tune the surface properties. O2 plasma etching increased the
sensitivity due to increased surface oxygen content but did not affect surface
roughness while the antistatic gun treatment increased surface roughness but not
oxygen content. The effect of tissue fouling on CNT yarns was studied for the
first time, and the relatively hydrophilic surface after O2 plasma etching
provided better resistance to fouling than unmodified or antistatic gun treated
CNTYMEs. Overall, O2 plasma etching and antistatic gun treatment improve the
sensitivity of CNTYMEs by different mechanisms, providing the possibility to tune
the CNTYME surface and enhance sensitivity.
PMID- 28423893
TI - The Least Stable Isomer of BN Naphthalene: Toward Predictive Trends for the
Optoelectronic Properties of BN Acenes.
AB - The least stable isomer of the parental BN naphthalene series has been
synthesized in a simple four-step sequence. Its experimental electronic structure
characterization via UV-PES, cyclic voltammetry, and UV-vis spectroscopy in
direct comparison with three other known BN naphthalene isomers has established
two guiding principles for predicting the electronic structures of BN acene
compounds: (1) Orientational BN isomers have similar HOMO-LUMO gaps. (2) For each
pair of orientational BN isomers, the more thermodynamically stable compound has
the lower HOMO energy. Furthermore, we demonstrate that BN/CC isosterism in the
context of BN-9,1-Naph can impact crystal packing to favor a cofacial pi-stack
motif.
PMID- 28423894
TI - Stratification and Size Segregation of Ternary and Polydisperse Colloidal
Suspensions during Drying.
AB - We investigate the drying process of three-component and polydisperse colloidal
suspensions using Brownian dynamics simulations. We have previously reported
(Phys. Rev. Lett. 2016, 116, 118301) on the drying of binary mixtures. For binary
mixtures, we found that a gradient of colloidal osmotic pressure develops during
drying and that this leads to the final film being stratified with a layer of
smaller particles on top of a layer of larger particles. Here, we find that
stratification by size is very general and also occurs in ternary and
polydisperse mixtures. We name the segregation effect colloidal diffusiophoresis.
In particular, we show that by changing the composition of a ternary mixture,
different stratification morphologies can be achieved and hence the film
properties can be tuned. In polydisperse spheres, colloidal diffusiophoresis
leads to enrichment in the large particles at the bottom part of the film,
whereas the top part is enriched with smaller particles. This segregation means
that in the final film, the particle size distribution depends on height. Thus,
the properties of the film will then depend on height. We propose a model that
predicts a power-law dependence of the phoretic velocity on particle size.
Results from the model and simulation show a good agreement.
PMID- 28423895
TI - Supramolecularly Engineered pi-Amphiphile.
AB - This article describes self-assembly of supramolecularly engineered naphthalene
diimide (NDI)-derived amphiphiles NDI-1 and NDI-2. They have the same
hydrophobic/hydrophilic balance but merely differ by a single functional group,
amide or ester. They exhibit distinct self-assembly in water; NDI-1 forms
hydrogel, which upon aging forms crystals, whereas NDI-2 forms micelles as
revealed by in-depth structural analysis using cryo-TEM, dynamic light
scattering, and small-angle X-ray scattering studies. These results suggest that
the H-bonding among the amide groups fully regulates the self-assembly by
overruling the packing parameters. Further, the present study elucidates sharp
lower critical solution temperature exhibited by these pi-amphiphiles, which has
been extensively studied for many important applications of water-soluble
polymers but hardly known in the literature of small-molecule surfactants.
Control experiments with the same water-soluble hydrophilic wedge did not show
such a property, confirming this to be a consequence of the supramolecular
polymerization by extended amide-amide H-bonding and not inherent to the
structure of the hydrophilic wedge containing oligo-oxyethylene chains.
PMID- 28423896
TI - Synthesis, Structure, and Catalysis of Palladium Complexes Bearing a Group 13
Metalloligand: Remarkable Effect of an Aluminum-Metalloligand in Hydrosilylation
of CO2.
AB - Efficient synthesis and catalysis of a series of palladium complexes having a
group 13 metalloligand (Al, Ga, In) are reported utilizing 6,6"
bis(phosphino)terpyridine as a new scaffold for Pd-E bonds (E = Al, Ga, In).
Systematic investigation revealed unique characteristics of the Al-metalloligand
in both structure and reactivity, which exhibited the highest catalytic activity
for hydrosilylation of CO2 ever reported (TOF = 19 300 h-1). This study
demonstrated fine-tuning of catalyst activity by the precisely designed
metalloligand is a promising approach for new catalyst development in synthetic
organometallic chemistry.
PMID- 28423897
TI - Orders of Magnitude Reduction of Rapid Coagulation Rate with Decreasing Size of
Silica Nanoparticles.
AB - The modification of the classical Smoluchowski theory for the rapid coagulation
rate of colloidal particles, which takes account of the effect of the squeezing
flow between colliding particles, has been widely accepted because it predicts
experimental results adequately. However, it is not clear whether the modified
theory, in which the coagulation rate is independent of the particle size, is
applicable even to nanoparticles in solutions. In the present study, the rapid
coagulation rates of silica particles in various 2 M chloride and 1 M potassium
solutions were measured by using a low-angle light-scattering apparatus, and the
dependence of rapid coagulation rate on the particle diameter, Dp, was
investigated extensively. It was clearly shown that the rapid coagulation rate of
spherical silica particles reduces by the orders of magnitude with decreasing
particle size at Dp <= 300 nm, whereas it coincides with the value predicted by
the modified theory at Dp >= 300 nm. A possible mechanism is proposed, and an
analytical equation, which predicts the dramatic reduction in the rapid
coagulation rate with decreasing particle size, is derived.
PMID- 28423898
TI - Spotlights: Volume 8, Issue 8.
PMID- 28423899
TI - Viewpoints on the 2017 Pacific Conference on Spectroscopy and Dynamics.
PMID- 28423901
TI - Estimation of Nanodiamond Surface Charge Density from Zeta Potential and
Molecular Dynamics Simulations.
AB - Molecular dynamics simulations of nanoparticles (NPs) are increasingly used to
study their interactions with various biological macromolecules. Such simulations
generally require detailed knowledge of the surface composition of the NP under
investigation. Even for some well-characterized nanoparticles, however, this
knowledge is not always available. An example is nanodiamond, a nanoscale diamond
particle with surface dominated by oxygen-containing functional groups. In this
work, we explore using the harmonic restraint method developed by Venable et al.,
to estimate the surface charge density (sigma) of nanodiamonds. Based on the Gouy
Chapman theory, we convert the experimentally determined zeta potential of a
nanodiamond to an effective charge density (sigmaeff), and then use the latter to
estimate sigma via molecular dynamics simulations. Through scanning a series of
nanodiamond models, we show that the above method provides a straightforward
protocol to determine the surface charge density of relatively large (> ~100 nm)
NPs. Overall, our results suggest that despite certain limitation, the above
protocol can be readily employed to guide the model construction for MD
simulations, which is particularly useful when only limited experimental
information on the NP surface composition is available to a modeler.
PMID- 28423902
TI - Tribute to Klaus Schulten.
PMID- 28423900
TI - Methodology for the Simulation of Molecular Motors at Different Scales.
AB - Millisecond-scale conformational transitions represent a seminal challenge for
traditional molecular dynamics simulations, even with the help of high-end
supercomputer architectures. Such events are particularly relevant to the study
of molecular motors-proteins or abiological constructs that convert chemical
energy into mechanical work. Here, we present a hybrid-simulation scheme
combining an array of methods including elastic network models, transition path
sampling, and advanced free-energy methods, possibly in conjunction with
generalized-ensemble schemes to deliver a viable option for capturing the
millisecond-scale motor steps of biological motors. The methodology is already
implemented in large measure in popular molecular dynamics programs, and it can
leverage the massively parallel capabilities of petascale computers. The
applicability of the hybrid method is demonstrated with two examples, namely
cyclodextrin-based motors and V-type ATPases.
PMID- 28423903
TI - Biography of Klaus Schulten.
PMID- 28423904
TI - Colleagues of Klaus Schulten.
PMID- 28423905
TI - Abbreviated Curriculum Vitae of Klaus Schulten.
PMID- 28423906
TI - Selected Publications of Klaus Schulten.
PMID- 28423907
TI - Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human
DNA Polymerase eta.
AB - Human DNA polymerase eta (Pol eta) plays a vital role in protection against skin
cancer caused by damage from ultraviolet light. This enzyme rescues stalled
replication forks at cyclobutane thymine-thymine dimers (TTDs) by inserting
nucleotides opposite these DNA lesions. Residue R61 is conserved in the Pol eta
enzymes across species, but the corresponding residue, as well as its neighbor
S62, is different in other Y-family polymerases, Pol iota and Pol kappa. Herein,
R61 and S62 are mutated to their Pol iota and Pol kappa counterparts. Relative
binding free energies of dATP to mutant Pol eta*DNA complexes with and without a
TTD were calculated using thermodynamic integration. The binding free energies of
dATP to the Pol eta*DNA complex with and without a TTD are more similar for all
of these mutants than for wild-type Pol eta, suggesting that these mutations
decrease the ability of this enzyme to distinguish between a TTD lesion and
undamaged DNA. Molecular dynamics simulations of the mutant systems provide
insights into the molecular level basis for the changes in relative binding free
energies. The simulations identified differences in hydrogen-bonding, cation-pi,
and pi-pi interactions of the side chains with the dATP and the TTD or thymine
thymine (TT) motif. The simulations also revealed that R61 and Q38 act as a clamp
to position the dATP and the TTD or TT and that the mutations impact the balance
among the interactions related to this clamp. Overall, these calculations suggest
that R61 and S62 play key roles in the specificity and effectiveness of Pol eta
for bypassing TTD lesions during DNA replication. Understanding the basis for
this specificity is important for designing drugs aimed at cancer treatment.
PMID- 28423909
TI - Ripping RNA by Force Using Gaussian Network Models.
AB - Using force as a probe to map the folding landscapes of RNA molecules has become
a reality thanks to major advances in single molecule pulling experiments.
Although the unfolding pathways under tension are complicated to predict, studies
in the context of proteins have shown that topology is the major determinant of
the unfolding landscapes. By building on this finding we study the responses of
RNA molecules to force by adapting Gaussian network model (GNM) that represents
RNAs using a bead-spring network with isotropic interactions. Cross-correlation
matrices of residue fluctuations, which are analytically calculated using GNM
even upon application of mechanical force, show distinct allosteric communication
as RNAs rupture. The model is used to calculate the force-extension curves at
full thermodynamic equilibrium, and the corresponding unfolding pathways of four
RNA molecules subject to a quasi-statically increased force. Our study finds that
the analysis using GNM captures qualitatively the unfolding pathway of T.
ribozyme elucidated by the optical tweezers measurement. However, the simple
model cannot capture features, such as bifurcation in the unfolding pathways or
the ion effects, in the forced-unfolding of RNAs.
PMID- 28423908
TI - Dependence of the Enzymatic Velocity on the Substrate Dissociation Rate.
AB - Enzymes are biological catalysts that play a fundamental role in all living
systems by supporting the selectivity and the speed for almost all cellular
processes. While the general principles of enzyme functioning are known, the
specific details of how they work at the microscopic level are not always
available. Simple Michaelis-Menten kinetics assumes that the enzyme-substrate
complex has only one conformation that decays as a single exponential. As a
consequence, the enzymatic velocity decreases as the dissociation (off) rate
constant of the complex increases. Recently, Reuveni et al. [ Proc. Natl. Acad.
Sci. USA 2014 , 111 , 4391 - 4396 ] showed that it is possible for the enzymatic
velocity to increase when the off rate becomes higher, if the enzyme-substrate
complex has many conformations which dissociate with the same off rate constant.
This was done using formal mathematical arguments, without specifying the nature
of the dynamics of the enzyme-substrate complex. In order to provide a physical
basis for this unexpected result, we derive an analytical expression for the
enzymatic velocity assuming that the enzyme-substrate complex has multiple states
and its conformational dynamics is described by rate equations with arbitrary
rate constants. By applying our formalism to a complex with two conformations, we
show that the unexpected off rate dependence of the velocity can be readily
understood: If one of the conformations is unproductive, the system can escape
from this "trap" by dissociating, thereby giving the enzyme another chance to
form the productive enzyme-substrate complex. We also demonstrate that the
nonmonotonic off rate dependence of the enzymatic velocity is possible not only
when all off rate constants are identical, but even when they are different. We
show that for typical experimentally determined rate constants, the nonmonotonic
off rate dependence can occur for micromolar substrate concentrations. Finally,
we discuss the relation of this work to the problem of optimizing the flux
through singly occupied membrane channels and transporters.
PMID- 28423910
TI - Conformational Preference of Serogroup B Salmonella O Polysaccharide in Presence
and Absence of the Monoclonal Antibody Se155-4.
AB - Salmonella infection is a major public health problem worldwide. Antibodies
directed toward the O polysaccharide (OPS) of S. Typhimurium, a serogroup B
nontyphoidal Salmonella serovar, have protected against fatal infection in animal
models. The OPS is known to undergo O-acetylation, though the impact of these
modifications on antibody binding is poorly understood. Using molecular
simulations, we assessed the conformational properties and antigen-antibody
interactions of deacetylated and O-acetylated S. Typhimurium OPS when bound by
monoclonal anti-OPS IgG Se155-4. Our findings indicate that (i) the alpha-d
abequose (8) monosaccharide makes important interactions with Se155-4, (ii) the
deacetylated form binds to the antibody in two conformations, (iii) the acetyl
group at alpha-l-rhamnose (5) traps the acetylated O-antigenic saccharide in one
of those two conformations when bound to the antibody; (iv) the dominant
conformation sampled by both unbound saccharides only occurs in the deacetylated
antibody complex; and (v) both unbound saccharides sample the second bound
conformation to a small extent (2-4%). These observations provide insights into
the conformational preference of an antigenic saccharide when bound to a well
characterized specific monoclonal antibody, and suggest possible important
properties of vaccine induced antibodies following immunization with live
attenuated and OPS-based subunit vaccines.
PMID- 28423911
TI - Token Economy: A Systematic Review of Procedural Descriptions.
AB - The token economy is a well-established and widely used behavioral intervention.
A token economy is comprised of six procedural components: the target
response(s), a token that functions as a conditioned reinforcer, backup
reinforcers, and three interconnected schedules of reinforcement. Despite decades
of applied research, the extent to which the procedures of a token economy are
described in complete and replicable detail has not been evaluated. Given the
inherent complexity of a token economy, an analysis of the procedural
descriptions may benefit future token economy research and practice. Articles
published between 2000 and 2015 that included implementation of a token economy
within an applied setting were identified and reviewed with a focus on evaluating
the thoroughness of procedural descriptions. The results show that token economy
components are regularly omitted or described in vague terms. Of the articles
included in this analysis, only 19% (18 of 96 articles reviewed) included
replicable and complete descriptions of all primary components. Missing or vague
component descriptions could negatively affect future research or applied
practice. Recommendations are provided to improve component descriptions.
PMID- 28423912
TI - Antifungal activity of cinnamic acid and benzoic acid esters against Candida
albicans strains.
AB - Candida albicans is an important opportunistic fungal pathogen capable of
provoking infection in humans. In the present study, we evaluated the antifungal
effect of 23 ester derivatives of the cinnamic and benzoic acids against 3 C.
albicans strains (ATCC-76645, LM-106 and LM-23), as well as discuss their
Structure-Activity Relationship (SAR). The antifungal assay results revealed that
the screened compounds exhibited different levels of activity depending on
structural variation. Among the ester analogues, methyl caffeate (5) and methyl 2
nitrocinnamate (10) were the analogues that presented the best antifungal effect
against all C. albicans strains, presenting the same MIC values (MIC = 128
MUg/mL), followed by methyl biphenyl-2-carboxylate (21) (MIC = 128, 128 and 256
MUg/mL for C. albicans LM-106, LM-23, and ATCC-76645, respectively). Our results
suggest that certain molecular characteristics are important for the antifungal
action.
PMID- 28423913
TI - Application of IATA - A case study in evaluating the global and local performance
of a Bayesian network model for skin sensitization.
AB - The information characterizing key events in an Adverse Outcome Pathway (AOP) can
be generated from in silico, in chemico, in vitro and in vivo approaches.
Integration of this information and interpretation for decision making are known
as integrated approaches to testing and assessment (IATA). One such IATA was
published by Jaworska et al., which describes a Bayesian network model known as
ITS-2. The current work evaluated the performance of ITS-2 using a stratified
cross-validation approach. We also characterized the impact of replacing the most
significant component of the network, output from the expert system TIMES-SS,
with structural alert information from the OECD Toolbox and Toxtree. Lack of
structural alerts or TIMES-SS predictions yielded a sensitization potential
prediction of 79%. If the TIMES-SS prediction was replaced by a structural alert
indicator, the network predictivity increased up to 87%. The original network's
predictivity was 89%. The local applicability domain of the original ITS-2
network was also evaluated using reaction mechanistic domains to understand what
types of chemicals ITS-2 was able to make the best predictions for. We found that
the original network was successful at predicting which chemicals would be
sensitizers, but not at predicting their potency.
PMID- 28423914
TI - Current views on neuropeptide Y and diabetes-related atherosclerosis.
AB - Diabetes-induced atherosclerotic cardiovascular disease is the leading cause of
death of diabetic patients. Neuronal regulation plays a critical role in glucose
metabolism and cardiovascular function under physiological and pathological
conditions, among which, neurotransmitter neuropeptide Y has been shown to be
closely involved in these two processes. Elevated central neuropeptide Y level
promotes food intake and reduces energy expenditure, thereby increasing
adiposity. Neuropeptide Y is co-localized with noradrenaline in central and
sympathetic nervous systems. As a major peripheral vascular contractive
neurotransmitter, through interactions with its receptors, neuropeptide Y has
been implicated in the pathology and progression of diabetes, by promoting the
proliferation of endothelial cells and vascular fibrosis, which may contribute to
diabetes-induced cardiovascular disease. Neuropeptide Y also participates in the
pathogenesis of atherosclerosis, the major form of cardiovascular disease, via
aggravating endothelial dysfunction, growth of vascular smooth muscle cells,
formation of foam cells and platelets aggregation. This review highlights the
causal role of neuropeptide Y and its receptor system in the development of
diabetes mellitus and one of its complications: atherosclerotic cardiovascular
disease. The information from this review provides both critical insights onto
the mechanisms underlying the pathogenesis of atherosclerosis and evidence for
the development of therapeutic strategies.
PMID- 28423915
TI - Isolation of flavonoids from apple peel using novel graphene oxide cotton fiber.
AB - A novel graphene oxide cotton fibre (GOF) was used to adsorb flavonoids from
crude ethanol extracts derived from apple peels. Ultra-high pressure liquid
chromatography-mass spectrometry was used to analyse polyphenol content, and the
resulting data demonstrated that GOF-based flash chromatography can be used to
efficiently separate polyphenols from sugars and can facilitate the removal of
95% of the sugar content. Flavonoids can be easily separated from phenolic acids.
Chalcones and flavonols were eluted with 100% methanol and subsequently flavan-3
ols can be eluted with 0.04 M sodium hydroxide. The novel GOF has the potential
to be used in the isolation of flavonoids.
PMID- 28423916
TI - Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and
Evidence-Based Management.
AB - OBJECTIVE: To review the incidence, risk factors, and management of pegfilgrastim
induced bone pain (PIBP). DATA SOURCES: PubMed was searched from 1980 to March
31, 2017, using the terms pegfilgrastim and bone pain. STUDY SELECTION AND DATA
EXTRACTION: English-language, human studies and reviews assessing the incidence,
risk factors, and management of PIBP were incorporated. DATA SYNTHESIS: A total
of 3 randomized, prospective studies and 2 retrospective studies evaluated
pharmacological management of PIBP. Naproxen compared with placebo demonstrated a
reduction in the degree, incidence, and duration of bone pain secondary to
pegfilgrastim. Loratadine was not effective in reducing the incidence of bone
pain prophylactically, but a retrospective study evaluating dual antihistamine
blockade with loratadine and famotidine demonstrated a decreased incidence in
bone pain when administered before pegfilgrastim. CONCLUSION: Naproxen is
effective at managing PIBP. Although commonly used, antihistamines have a paucity
of data supporting their use. Dose reductions of pegfilgrastim and opioids may
also be potential management options; however, data supporting these treatment
modalities are scarce.
PMID- 28423917
TI - Management of Opioid-Induced Constipation in Hospice Patients.
AB - BACKGROUND: Constipation is a common symptom in patients with advanced disease
taking opioids. Opioid-induced constipation (OIC) is commonly treated with
laxatives and stool softeners. Recently, newer agents have come to market which
broaden options for patients in whom first-line therapies are not effective.
OBJECTIVE: To determine what pharmacologic regimens are currently used in hospice
programs to prevent and treat OIC, whether those regimens have changed with the
introduction of newer agents and evidence discouraging the use of docusate, and
whether hospice programs are standardizing the management of OIC. METHODS: An
online 10-item questionnaire was disseminated by the National Hospice and
Palliative Care Organization. Questions addressed demographics; first-, second-
and third-line pharmacologic treatments included in bowel protocols; whether
prescribing practices have changed in the last 5 years; and percentage of
patients receiving specific constipation therapies. RESULTS: The majority of
organizations (68.8%) responded that at least 90% of patients were prescribed a
bowel regimen on admission to hospice and 84.4% stated that they have a guideline
or protocol for managing OIC. The most commonly used preparations for the
treatment of OIC for patients during their length of stay in hospice were senna
plus docusate, senna alone, docusate alone, bisacodyl, polyethylene glycol 3350,
and lactulose. Over 75% of hospice organizations claimed they never used
methylnaltrexone, linaclotide, lubiprostone, or naloxegol. CONCLUSION: This
survey provides insight into recent practices of hospice organizations in the
treatment of OIC. As more agents come to market, it is likely that management of
OIC will continue to evolve.
PMID- 28423919
TI - Joint attention difficulties in autistic adults: An interactive eye-tracking
study.
AB - Joint attention - the ability to coordinate attention with a social partner - is
critical for social communication, learning and the regulation of interpersonal
relationships. Infants and young children with autism demonstrate impairments in
both initiating and responding to joint attention bids in naturalistic settings.
However, little is known about joint attention abilities in adults with autism.
Here, we tested 17 autistic adults and 17 age- and nonverbal intelligence
quotient-matched controls using an interactive eye-tracking paradigm in which
participants initiated and responded to joint attention bids with an on-screen
avatar. Compared to control participants, autistic adults completed fewer trials
successfully. They were also slower to respond to joint attention bids in the
first block of testing but performed as well as controls in the second block.
There were no group differences in responding to spatial cues on a non-social
task with similar attention and oculomotor demands. These experimental results
were mirrored in the subjective reports given by participants, with some
commenting that they initially found it challenging to communicate using eye
gaze, but were able to develop strategies that allowed them to achieve joint
attention. Our study indicates that for many autistic individuals, subtle
difficulties using eye-gaze information persist well into adulthood.
PMID- 28423918
TI - Expanding the Palliative Care Domains to Meet the Needs of a Community-Based
Supportive Care Model.
AB - BACKGROUND: Whole person care is appropriate for seriously ill persons. The
current framework of palliative care domains in the National Consensus Project
(NCP) Guidelines for Quality Palliative Care offers an opportunity to reassess
the domains of care delivered at home, earlier in the course of illness.
OBJECTIVE: This qualitative study was used to test the applicability of a
proposed, expanded set of domains. The results were used to inform a home-based,
upstream model of supportive care for serious illness. METHODS: Quotes relating
to the experience of late-life serious illness were derived from transcripts of
12 semi-structured group interviews conducted with patients, family, and
professionals. Quotes originally coded to the NCP domains of palliative care were
then coded to the proposed domain set, which included new categories of
family/caregiver, legal/financial, and legacy/bereavement domains. RESULTS: A
total of 489 quotes were assigned to the proposed expanded set of domains. One
hundred one (19%) coded to the family/caregiver domain, 28 (5%) to the
legacy/bereavement domain, and 27 (5%) to the legal/financial domain. Ninety
seven (87%) of the 111 quotes coded to family/caregiver had been initially coded
to the NCP social aspects of care. Family/caregiver themes included challenges,
rewards, insights, and family growth. CONCLUSION: The preponderance of family
related issues suggests that including the family domain may promote recognition
and support of family caregivers and the services they provide. Although this
study provides some support for including the legacy/bereavement and
legal/financial domains, additional research is needed to determine whether there
is a basis for including them in the domain structure.
PMID- 28423920
TI - 'Medical' marijuana is incompatible with mental health promotion.
PMID- 28423921
TI - Phytochemical investigations and evaluation of antimutagenic activity of the
alcoholic extract of Glycosmis pentaphylla and Tabernaemontana coronaria by Ames
test.
AB - Chemical investigation of root bark of Glycosmis pentaphylla and stem bark of
Tabernaemontana coronaria led to the isolation of three carbazole alkaloids
glycozoline, glycozolidine and methyl carbazole 3-carboxylate, two furoquinoline
alkaloids skimmianine and dictamine, an acridone alkaloid arborinine, three
monomeric indole alkaloids coronaridine, 10-methoxy coronaridine and
tabernaemontanine, and two dimeric indole alkaloids voacamine and
tabernaelegantine B. Their structures were established by detailed spectral
analysis. Mutagenic and antimutagenic potential of methanol extract of both plant
materials were evaluated by Ames test against known positive mutagens 2
aminofluorine, 4-nitro-O-phenylenediamine and sodium azide using Salmonella
typhimurium TA 98 and TA 100 bacterial strains both in the presence and absence
of S9. Both the extracts were non-mutagenic in nature. Both the extracts of G.
pentaphylla and T. coronaria exhibited significant antimutagenic activity against
NPD and sodium azide for S. typhimurium TA98 and TA100 strains. The results
indicated that the extracts could counteract the mutagenicity induced by
different genotoxic compounds.
PMID- 28423922
TI - Activation of GPR15 and its involvement in the biological effects of smoking.
AB - Smoking is one of the most significant modifiable environmental risk factors for
many diseases. Smoking causes excessive mortality worldwide. Despite decades of
long research, there has not been a clear understanding regarding the molecular
mechanism that makes smoking harmful to health. Some recent studies have found
that smoking influences most significantly the expression and methylation of
GPR15. GPR15 is an orphan receptor that is involved in the regulation of the
innate immunity and the T-cell trafficking in the intestinal epithelium. Further
studies have confirmed that GPR15 is very strongly involved in smoking and
smoking-induced molecular changes. Therefore, the altered expression and
epigenetic regulation of GPR15 could have a significant role in the health impact
of smoking. Impact statement The review describes an orphan receptor GPR15 that
has recently been found to be influenced by smoking. This makes GPR15 very
sensitive and adequate biomarker for smoking and smoking studies. Also,
activation of GPR15 by smoking could help to explain its effects on health.
PMID- 28423923
TI - A new wortmannine derivative from a Tripterygium wilfordii endophytic fungus
Talaromyces wortmannii LGT-4.
AB - A new wortmannine derivative named wortmannine E (1) was isolated from
Talaromyces wortmannii LGT-4, an endophytic fungus of Tripterygium wilfordii. Its
structure was established by 1D and 2D NMR spectra.
PMID- 28423924
TI - Advances in siRNA delivery in cancer therapy.
AB - RNA interference (RNAi)-based therapeutic approaches are under vibrant
scrutinisation to seek cancer cure. siRNA suppress expression of the carcinogenic
genes by targeting the mRNA expression. However, in vivo systemic siRNA therapy
is hampered by the barriers such as poor cellular uptake, instability under
physiological conditions, off-target effects and possible immunogenicity. To
overcome these challenges, systemic siRNA therapy warrants the development of
clinically suitable, safe, and effective drug delivery systems. Herein, we review
the barriers, potential siRNA drug delivery systems, and application of siRNA in
clinical trials for cancer therapy. Further research is required to harness the
full potential of siRNA as a cancer therapeutic.
PMID- 28423925
TI - Antioxidant and alpha-glucosidase inhibitory activities of isoflavonoids from the
rhizomes of Ficus tikoua Bur.
AB - A new unique isoflavone derivatives with a cyclic-monoterpene-substituent,
ficusin C (1), together with five known compounds (2-6), were isolated from the
rhizomes of Ficus tikoua. Their structures were elucidated on the basis of
spectroscopic data interpretation, mass spectrometric analysis and comparison
with literature data of related compounds. Antioxidant and alpha-glucosidase
inhibitory activities of these compounds were evaluated by 1,1-diphenyl-2
picryhydrazyl (DPPH) radical-scavenging assay and alpha-glucosidase inhibitory
experiment, respectively.
PMID- 28423926
TI - Antibacterial activity of a triterpenoid saponin from the stems of Caesalpinia
pulcherrima Linn.
AB - A new compound 1 was isolated from the methanolic extract of the stems of the
Caesalpinia pulcherrima Linn. along with a reported compound (2) 3-O-beta-D
glucopyranosyl-(1->4)-beta-D-xylopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)
alpha-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D
glucopyranosyl ester. The new compound 1 has m.p. 272-274 degrees C, m.f.
C46H74O17, [M]+ m/z 898. It was characterised as 3-O-beta-D-glucopyranosyl-(1->4)
alpha-L-arabinopyranosyl hederagenin 28-O-beta-D- xylopyranosyl ester by various
colour reactions, chemical degradations and spectral analyses. Antibacterial
activity of compound 1 was screened against various Gram-positive and Gram
negative bacteria and showed significant results.
PMID- 28423927
TI - The Nation's Disaffected and Workplace Health Promotion.
PMID- 28423928
TI - Engaging Parents to Promote Children's Nutrition and Health.
AB - PURPOSE: Using the Academy of Nutrition and Dietetics benchmarks as a framework,
this study examined childcare providers' (Head Start [HS], Child and Adult Care
Food Program [CACFP] funded, and non-CACFP) perspectives regarding communicating
with parents about nutrition to promote children's health. DESIGN: Qualitative.
SETTING: State-licensed center-based childcare programs. PARTICIPANTS: Full-time
childcare providers (n = 18) caring for children 2 to 5 years old from varying
childcare contexts (HS, CACFP funded, and non-CACFP), race, education, and years
of experience. METHODS: In-person interviews using semi-structured interview
protocol until saturation were achieved. Thematic analysis was conducted.
RESULTS: Two overarching themes were barriers and strategies to communicate with
parents about children's nutrition. Barriers to communication included-(a)
parents are too busy to talk with providers, (b) parents offer unhealthy foods,
(c) parents prioritize talking about child food issues over nutrition, (d)
providers are unsure of how to communicate about nutrition without offending
parents, and (e) providers are concerned if parents are receptive to nutrition
education materials. Strategies for communication included-(a) recognize the
benefits of communicating with parents about nutrition to support child health,
(b) build a partnership with parents through education, (c) leverage policy
(federal and state) to communicate positively and avoid conflict, (d) implement
center-level practices to reinforce policy, and (e) foster a respectful
relationship between providers and parents. CONCLUSION: Policy and environmental
changes were recommended for fostering a respectful relationship and building a
bridge between providers and parents to improve communication about children's
nutrition and health.
PMID- 28423930
TI - The Art of Health Promotion ideas for improving health outcomes.
PMID- 28423931
TI - Comparative Effectiveness of Two Walking Interventions on Participation, Step
Counts, and Health.
AB - PURPOSE: To (1) compare the effects of two worksite-based walking interventions
on employee participation rates; (2) compare average daily step counts between
conditions, and; (3) examine the effects of increases in average daily step
counts on biometric and psychologic outcomes. DESIGN: We conducted a cluster
randomized trial in which six employer groups were randomly selected and randomly
assigned to condition. SETTING: Four manufacturing worksites and two office-based
worksite served as the setting. SUBJECTS: A total of 474 employees from six
employer groups were included. INTERVENTION: A standard walking program was
compared to an enhanced program that included incentives, feedback, competitive
challenges, and monthly wellness workshops. MEASURES: Walking was measured by
self-reported daily step counts. Survey measures and biometric screenings were
administered at baseline and 3, 6, and 9 months after baseline. ANALYSIS:
Analysis used linear mixed models with repeated measures. RESULTS: During 9
months, participants in the enhanced condition averaged 726 more steps per day
compared with those in the standard condition (p < .001). A 1000-step increase in
average daily steps was associated with significant weight loss for both men (
3.8 lbs.) and women (-2.1 lbs.), and reductions in body mass index (-0.41 men,
0.31 women). Higher step counts were also associated with improvements in mood,
having more energy, and higher ratings of overall health. CONCLUSIONS: An
enhanced walking program significantly increases participation rates and daily
step counts, which were associated with weight loss and reductions in body mass
index.
PMID- 28423932
TI - Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor
Tendon Repairs.
AB - BACKGROUND: The aim of the study was to compare biomechanical strength, repair
times, and repair values for zone II core flexor tendon repairs. METHODS: A total
of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index
through small finger and randomized into one of 5 repair groups: 4-stranded cross
stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double
Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double
stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided
suture). Repairs were measured in situ and their repair times were measured.
Tendons were linearly loaded to failure and multiple biomechanical values were
measured. The repair value was calculated based on operating room costs, repair
times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc
statistical analysis were used to compare repair data. RESULTS: The braided
cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the
4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to
perform. The total repair value was the highest for braided cruciate ( P > .05)
compared with all other repairs. Barbed suture did not outperform any repairs in
any categories. CONCLUSIONS: The braided cruciate was the strongest of the tested
flexor tendon repairs. The 2-mm gapping and maximum load to failure for this
repair approached similar historical strength of other 6- and 8-stranded repairs.
In this study, suture cost was negligible in the overall repair cost and should
be not a determining factor in choosing a repair.
PMID- 28423933
TI - Phytochemical composition and biological activities of Artemisia quettensis
Podlech ethanolic extract.
AB - The present study aim to investigate the phytochemical composition,
antibacterial, antioxidant and anticancer activities of the ethanolic extract
from aerial parts of Artemisia quettensis Podlech. The aerial part of A.
quettensis Podlech extract was used for Gas chromatography-mass spectrometry (GC
MS) analysis, antioxidant, antibacterial and anticancer activities. GC/MS
analysis of extract from this plant showed 23 major components and the most
dominant components were acetic acid, [4-(1-hydroxy-1-methylethyl) cyclohex-1
enyl] methyl ester (13.88%), trans-Phytol (10.06%) and 2,6-Dimethyl-2,6-octadiene
1,8-diol diacetate (6.8%). The extract had significant antibacterial and
anticancer effects. The highest percentage of antioxidant activity was 78.46% at
2 mg/mL concentration of extract. Moreover, the highest antibacterial effects of
extract were against to gram-positive bacteria and the IC50 cell cytotoxicity
value on HT29 cell line in 24 h, 48 h and 72 h were 31.54, 6.08 and 2.96 mg/mL,
respectively. From this study, A. quettensis Podlech could be considered as a
promising source for novel drug compounds.
PMID- 28423934
TI - Estimating Dementia and Receipt of Informal Care Using Behavioral Risk Factor
Surveillance System Data.
AB - INTRODUCTION: Estimates of US adults with dementia differ widely and don't
distinguish adults living in the community. METHODS: Behavioral Risk Factor
Surveillance System data from 120 485 households in 21 states that used a
cognitive decline module in 2011 were used. Data for both respondents and other
adults with subjective cognitive decline (SCD) were included through proxy
responses. Using responses to questions about the receipt of informal care for
their SCD and diagnosed dementia, estimates were made for each state. RESULTS:
Overall, 2.9% (range: 1.5% in Tennessee to 5.3% in Arkansas) of all
noninstitutionalized adults in these states received informal care for their SCD
and 0.9% (range: 0.5% in Tennessee to 2.0% in Arkansas) were estimated to have
dementia. Limiting results to respondents reduced estimates significantly.
DISCUSSION: Combined results for respondents and nonrespondents from a
representative telephone survey provide varying estimates of SCD-related measures
across states, highlighting the need for state-specific estimates.
PMID- 28423935
TI - Supporting Simple Activity Engagement in Persons With Moderate to Severe
Alzheimer's Disease Through a Technology-Aided Program.
AB - OBJECTIVES: These 2 studies assessed a technology-aided program to support mild
physical exercise or simple occupational activity in participants with moderate
to severe Alzheimer's disease. METHODS: Study 1 included 11 participants who were
to perform a leg-raising response. Study 2 included 10 participants who were to
sort objects into different containers. The program ensured that they received
positive stimulation contingent on the responses and reminders/prompts after
periods of nonresponding. Each study was carried out according to a nonconcurrent
multiple baseline design across participants. RESULTS: The program was successful
in supporting mild physical exercise and activity with objects in the 2 groups of
participants, respectively. The participants also showed signs of positive
involvement (eg, smiles and verbalizations) during the sessions. Moreover, staff
personnel rated the program and its impact positively. CONCLUSION: The program
may be considered a practical resource for supporting positive engagement in
persons with moderate to severe Alzheimer's disease.
PMID- 28423936
TI - Relationship Quality and Distress in Caregivers of Persons With Dementia: A Cross
Sectional Study.
AB - This cross-sectional study aimed to investigate the relationship between
caregivers and care receivers, defined as home-dwelling family members with
dementia. We used a self-rating questionnaire, the Felt Expressed Emotion Rating
Scale (FEERS; 6 simple questions), to measure caregiver perceptions of the care
receiver's criticisms (CCs) and emotional overinvolvement (EOI) toward the
caregiver. We performed factor analyses to rank single items on the FEERS
pertaining to CC and EOI. We included 208 caregiver/care receiver pairs. Logistic
regression analyses tested associations between FEERS items and caregiver and
care receiver variables. The main contributors to caregiver perceptions of CC
were the caregiver's own distress and the amount of time spent with the care
receiver. Socially distressed caregivers perceived the care receiver as
emotionally overinvolved. When offering a psychosocial intervention, a tailored
program should target the caregiver's perceived relationship with the family
member and the caregiver's distress. The program should also endeavor to give the
caretaker more opportunities for leisure time.
PMID- 28423937
TI - Concordance of Several Subcellular Interactions Initiates Alzheimer's Dementia:
Their Reversal Requires Combination Treatment.
AB - The pathogenesis of Alzheimer's disease involves multiple pathways that, at the
macrolevel, include decreased proliferation plus increased loss affecting
neurons, astrocytes, and capillaries and, at the subcellular level, involve
several elements: amyloid/amyloid precursor protein, presenilins, the unfolded
protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the
Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented
show the intimate, anatomical interactions between neurons, astrocytes, and
capillaries; the interactions between the several subcellular factors affecting
those cells; and the treatments that are currently available and that might
correct dysfunctions in the subcellular factors. Available treatments include
lithium, valproate, pioglitazone, erythropoietin, and prazosin. Since the
subcellular pathogenesis involves multiple interacting elements, combination
treatment would be more effective than administration of a single drug directed
at only 1 element. The overall purpose of this presentation is to describe the
pathogenesis in detail and to explain the proposed treatments.
PMID- 28423938
TI - Validation of the Turkish Version of the Quick Mild Cognitive Impairment Screen.
AB - BACKGROUND: The objective of this study was to validate the Turkish version of
the Quick Mild Cognitive Impairment (Q mci-TR) screen. METHODS: In total, 100
patients aged >=65 years referred to a geriatric outpatient clinic with memory
loss were included. The Q mci was compared to the Turkish versions of the
standardized Mini-Mental State Examination and the Montreal Cognitive Assessment
(MoCA). RESULTS: The Q mci-TR had higher accuracy than the MoCA in discriminating
subjective memory complaints (SMCs) from cognitive impairment (mild cognitive
impairment [MCI] or dementia), of borderline significance after adjusting for age
and education ( P = .06). The Q mci-TR also had higher accuracy than the MoCA in
differentiating MCI from SMC, which became nonsignificant after adjustment ( P =
.15). A similar pattern was shown for distinguishing MCI from dementia. Test
reliability for the Q mci-TR was strong. CONCLUSION: The Q mci-TR is a reliable
and useful screening tool for discriminating MCI from SMC and dementia in a
Turkish population.
PMID- 28423939
TI - Erratum: "The Inhibitory Effect of Abietic Acid on Melanoma Cancer Metastasis and
Invasiveness In Vitro and In Vivo".
PMID- 28423940
TI - Preoperative Risk Factors for Complications in Elective Ankle and Hindfoot
Reconstruction.
AB - BACKGROUND: The purpose of this study was to examine medical, social, and
psychological factors associated with complications and reoperation after foot
and ankle reconstruction. METHODS: A retrospective chart review was conducted of
132 patients (135 feet; 139 operative cases) who had elective foot and ankle
reconstruction. Medical, social, and psychological variables were documented.
Primary outcomes included complications and reoperations. RESULTS: The overall
complication rate was 28% (39/139), and the reoperation rate was 17% (24/139).
Alcohol use (P = .03) and preoperative narcotic use (P = .02) were risk factors
for complications, with delayed wound healing more frequent in alcohol users (P =
.03) and deep infection (P = .045) and nonunion (P = .046) more frequent
preoperative narcotic use. Deep infection also was more frequent in tobacco users
(P < .01). Older patients were less likely to undergo reoperation (risk of
reoperation increased with age). Other variables were not associated with
increased complications. CONCLUSION: Patients who consumed alcohol or had been
prescribed any amount of narcotic within 3 months preoperatively were at
increased risk for complications. Patients who smoked were more likely to have a
wound infection. Surgeons should be aware of these factors and counsel patients
before surgery. LEVELS OF EVIDENCE: Level III: Retrospective comparative study.
PMID- 28423941
TI - Guide Pin Placement Technique for Total Ankle Replacement in Patients Who Had
Ipsilateral Total Knee Arthroplasty.
AB - : We describe a simple technique for guide pin placement for total ankle
replacement in patients who underwent previous ipsilateral total knee
arthroplasty. LEVELS OF EVIDENCE: Level V.
PMID- 28423942
TI - Natural gums of plant origin as edible coatings for food industry applications.
AB - Natural plant-based gums and their derivatives are widely utilized in food
industries, however, their applications as edible coatings to extend fresh fruits
and vegetable shelf-life has been explored recently. These natural polymeric
polysaccharides have many advantages as compared to synthetic polymers, because
they are biodegradable, nontoxic, economical and easily available in the
environment. Natural gums can also be semi synthetically modified to produce
derivatives, which can easily compete with the synthetic preservatives available
on the food market. In this review, the recent developments in the use of natural
gums and their derivatives as edible coatings have been explored and discussed.
PMID- 28423943
TI - High value added lipids produced by microorganisms: a potential use of sugarcane
vinasse.
AB - This review aims to present an innovative concept of high value added lipids
produced by heterotrophic microorganisms, bacteria and fungi, using carbon
sources, such as sugars, acids and alcohols that could come from sugarcane
vinasse, which is the main byproduct from ethanol production that is released in
the distillation step. Vinasse is a rich carbon source and low-cost feedstock
produced in large amounts from ethanol production. In 2019, the Brazilian
Ministry of Agriculture, Livestock and Food Supply estimates that growth of
ethanol domestic consumption will be 58.8 billion liters, more than double the
amount in 2008. This represents the annual production of more than 588 billion
liters of vinasse, which is currently used as a fertilizer in the sugarcane crop,
due to its high concentration of minerals, mainly potassium. However, studies
indicate some disadvantages such as the generation of Greenhouse Gas emission
during vinasse distribution in the crop, as well as the possibility of
contaminating the groundwater and soil. Therefore, the development of programs
for sustainable use of vinasse is a priority. One profitable alternative is the
fermentation of vinasse, followed by an anaerobic digester, in order to obtain
biomaterials such as lipids, other byproducts, and methane. Promising high value
added lipids, for instance carotenoids and polyunsaturated fatty acids (PUFAS),
with a predicted market of millions of US$, could be produced using vinasse as
carbon source, to guide an innovative concept for sustainable production. Example
of lipids obtained from the fermentation of compounds present in vinasse are
vitamin D, which comes from yeast sucrose fermentation and Omega 3, which can be
obtained by bacteria and fungi fermentation. Additionally, several other
compounds present in vinasse can be used for this purpose, including sucrose,
ethanol, lactate, pyruvate, acetate and other carbon sources. Finally, this paper
illustrates the potential market and microbial processes, using microorganisms,
for lipid production.
PMID- 28423944
TI - Emerging roles of long non-coding RNAs in plant response to biotic and abiotic
stresses.
AB - Spectacular progress in high-throughput transcriptome sequencing and expression
profiling using next-generation sequencing technologies have recently
revolutionized molecular biology and allowed massive advances in identifying the
genomic regions and molecular mechanisms underlying transcriptional regulation of
growth, development, and stress response. Through recent research, non-coding
RNAs, in particular long non-coding RNAs, have emerged as key regulators of
transcription in eukaryotes. Long non-coding RNAs are vastly heterogeneous groups
of RNAs that execute a broad range of essential roles in various biological
processes at the epigenetic, transcriptional, and post-transcriptional levels.
They modulate transcription through diverse mechanisms. Recently, numerous
lncRNAs have been identified to be associated with defense responses to biotic
and abiotic stresses. These have been suggested to perform indispensable roles in
plant immunity and adaptation to environmental conditions. However, only a few
lncRNAs have been functionally characterized in plants. In this paper, we
summarize the present knowledge of lncRNAs, review the recent advances in
understanding regulatory functions of lncRNAs, and highlight the emerging roles
of lncRNAs in regulating immune responses in plants.
PMID- 28423945
TI - On-line soft sensing in upstream bioprocessing.
AB - This review provides an overview and a critical discussion of novel possibilities
of applying soft sensors for on-line monitoring and control of industrial
bioprocesses. Focus is on bio-product formation in the upstream process but also
the integration with other parts of the process is addressed. The term soft
sensor is used for the combination of analytical hardware data (from sensors,
analytical devices, instruments and actuators) with mathematical models that
create new real-time information about the process. In particular, the review
assesses these possibilities from an industrial perspective, including sensor
performance, information value and production economy. The capabilities of
existing analytical on-line techniques are scrutinized in view of their
usefulness in soft sensor setups and in relation to typical needs in
bioprocessing in general. The review concludes with specific recommendations for
further development of soft sensors for the monitoring and control of upstream
bioprocessing.
PMID- 28423946
TI - Tween 80 surfactant-enhanced bioremediation: toward a solution to the soil
contamination by hydrophobic organic compounds.
AB - The occurrence of hydrophobic organic compounds (HOCs) in the soil has become a
highly significant environmental issue. This problem has been exacerbated by the
strong sorption of HOCs to the soils, which makes them unavailable for most
remediation processes. More and more works show that surfactant-enhanced
biological technologies offer a great potential to clear up HOCs-contaminated
soils. This article is a critical review of HOCs removal from soils using Tween
80 (one of the mostly used nonionic surfactants) aided biological remediation
technologies. The review begins with a discussion of the fundamentals of Tween 80
enhanced desorption of HOCs from contaminated soils, with special emphasis on the
biotoxicity of Tween 80. Successful results obtained by Tween 80-enhanced
microbial degradation and phytoremediation are documented and discussed in
section 3 and section 4, respectively. Results show Tween 80-enhanced
biotechnologies are promising for treating HOCs-contaminated soils. However,
considering the fact that most of these scientific studies have only been
conducted at the laboratory-scale, many improvements are required before these
technologies can be scaled up to the full-scale level. Moreover, further research
on mechanisms related to the interaction of Tween 80 with degrading
microorganisms and the plants is in high demand.
PMID- 28423947
TI - Metabolic engineering strategies for acetoin and 2,3-butanediol production:
advances and prospects.
AB - Acetoin and 2,3-butanediol (2,3-BD) have a large number of industrial
applications. The production of acetoin and 2,3-BD has traditionally relied on
oil supplies. Microbial production of acetoin and 2,3-BD will alleviate the
dependence on oil. Acetoin and 2,3-BD are neighboring metabolites in the 2,3-BD
metabolic pathway of bacteria. This review summarizes metabolic engineering
strategies for improvement of microbial acetoin and 2,3-BD production. We also
propose enhancements to current acetoin and 2,3-BD production strategies, by
offering a metabolic engineering approach that is guided by systems biology and
synthetic biology.
PMID- 28423948
TI - Fermentation at non-conventional conditions in food- and bio-sciences by the
application of advanced processing technologies.
AB - The interest in improving the yield and productivity values of relevant microbial
fermentations is an increasingly important issue for the scientific community.
Therefore, several strategies have been tested for the stimulation of microbial
growth and manipulation of their metabolic behavior. One promising approach
involves the performance of fermentative processes during non-conventional
conditions, which includes high pressure (HP), electric fields (EF) and
ultrasound (US). These advanced technologies are usually applied for microbial
inactivation in the context of food processing. However, the approach described
in this study focuses on the use of these technologies at sub-lethal levels,
since the aim is microbial growth and fermentation under these stress conditions.
During these sub-lethal conditions, microbial strains develop specific genetic,
physiologic and metabolic stress responses, possibly leading to fermentation
products and processes with novel characteristics. In some cases, these
modifications can represent considerable improvements, such as increased yields,
productivities and fermentation rates, lower accumulation of by-products and/or
production of different compounds. Although several studies report the successful
application of these technologies during the fermentation processes, information
on this subject is still scarce and poorly understood. For that reason, the
present review paper intends to assemble and discuss the main findings reported
in the literature to date, and aims to stimulate interest and encourage further
developments in this field.
PMID- 28423949
TI - Intranasal chitosan-g-HPbetaCD nanoparticles of efavirenz for the CNS targeting.
AB - Incompetence of antiretrovirals (ARV) in complete eradication of HIV from the CNS
is the biggest issue in neuro-AIDS treatment. The ineffectiveness is largely due
to the poor penetration of ARV. Hence, the present study is attempted to enhance
the CNS uptake of efavirenz (EFV) by designing intranasal EFV nanoparticles (EFV
NPs). EFV-NPs were fabricated using chitosan-g-HPbetaCD by ionic gelation method
and optimized using quadratic response surface methodology (RSM) employing two
factor, five-level circumscribed central composite design. NPs containing drug:
polymer ratio (1.25:0.79) were spherical with 198 +/- 4.4 nm size, 23.28 +/- 1.5%
drug loading and 38 +/- 1.43% entrapment efficiency. NPs showed sustained drug
release (99.03 +/- 0.30% in 8 h) and followed Fickian diffusion mechanism. It
gave 4.76 times greater permeability than plain drug solution through porcine
nasal mucosa. Enhanced CNS bioavailability (12.40-fold that of i.v solution) of
EFV, high drug-targeting percentage (99.24%) and drug-targeting index (141.3)
post-intranasal administration of NPs was observed. These results are
corroborated by gamma scintigraphy images, which revealed high CNS uptake. NPs
appeared histocompatible with porcine nasal mucosa and non-toxic to L929 cell
line. Thus, CS-g-HPbetaCD served as a potential carrier in developing intranasal
mucoadhesive EFV-NPs for the CNS targeting.
PMID- 28423951
TI - Preparation, characterization and dynamical mechanical properties of dextran
coated iron oxide nanoparticles (DIONPs).
AB - Dextran-coated iron oxide nanoparticles (DIONPs) with appropriate surface
chemistry exhibit many interesting properties that can be exploited in a variety
of biomedical applications such as magnetic resonance imaging (MRI) contrast
enhancement, tissue repair, hyperthermia, drug delivery and in cell separation.
This paper reports the experimental detail for preparation, characterization and
investigation of thermal and dynamical mechanical characteristics of the dextran
coated Fe3O4 magnetic nanoparticles. In our work, DIONPs were prepared in a 1:2
ratio of Fe(II) and Fe(III) salt in the HCl solution with NaOH at given
temperature. The obtained dextran-coated iron-oxide nanoparticles structure
property correlation was characterized by spectroscopic methods; attenuated total
reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and XRD. Coating
dextran on the iron-oxide proof of important peaks can be seen from the ATR-FTIR.
Dramatic crystallinity increment can be observed from the XRD pattern of the iron
oxide dextran nanoparticles. The thermal analysis was examined by differential
scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and differential
thermal analysis (DTA). Dynamical mechanical properties of dextran nanoparticles
were analysed by dynamic mechanical analysis (DMA). Thermal stability of the iron
oxide dextran nanoparticles is higher than that of the dextran.
PMID- 28423950
TI - Hepatoprotective and free radical scavenging actions of quercetin nanoparticles
on aflatoxin B1-induced liver damage: in vitro/in vivo studies.
AB - The objective of present study was in vitro and in vivo evaluation of
hepatoprotective and antioxidant activity of Quercetin nanoparticles (Q NPs)
against toxicity induced by aflatoxin B1. The Q NPs were prepared using
precipitation method. Hepatocytes were prepared by the method of collagenase
enzyme perfusion via portal vein. The NPs were characterized in terms of size and
morphology using dynamic light scattering (DLS) and transmission electron
microscopy (TEM), respectively. The level of parameters, such as cell death, ROS
formation, lipid peroxidation, mitochondrial membrane potential and cellular
glutathione (GSH) content, in the aflatoxin B1-treated and non-treated
hepatocytes were determined and the mentioned markers were assessed in the
presence of Q NPs. The prepared NPs showed particle size of 52.70 nm with
polydispersity index (PDI) of 0.18. In contrast to free Q, the administration of
Q NPs more efficiently decreased the rate of ROS formation, lipid peroxidation
and improved cell viability, mitochondrial membrane potential and glutathione
level and showed a significant hepatoprotective efiect by reducing levels of
aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. It
is suggested that the Q NPs is a promising candidate for drug delivery, which
enhances the hepatoprotective effect of Q against the cytotoxic effects of
aflatoxin B1.
PMID- 28423952
TI - Advances in the research of celery, an important Apiaceae vegetable crop.
AB - Celery (Apium graveolens L.), one of the most important vegetables in Apiaceae
family, is cultivated worldwide and utilized in food and cosmetic industries
because it is an excellent source of vitamins, phenolic compounds, volatile oils
and other nutrients. Celery extracts possess various medicinal properties, such
as antibacterial, anti-inflammatory and lowering blood glucose and serum lipid
levels. With the rapid advancements in molecular biology and sequencing
technology, studies on celery have been performed. Numerous molecular markers and
regulatory genes have been discovered and applied to improve celery. Research
advances, including genetic breeding, genomics research, function genes and
chemical composition, regarding celery are reviewed in this paper. Further
exploration and application trends are briefly described. This review provides a
reference for basic and applied research on celery, an important Apiaceae
vegetable crop.
PMID- 28423953
TI - Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal
tablets prepared by direct compression.
AB - The purpose of the present work was to evaluate polyvinyl alcohols (PVAs) as a
mucoadhesive polymer for mucoadhesive buccal tablets prepared by direct
compression. Various polymerization degree and particle diameter PVAs were
investigated for their usability. The tensile strength, in vitro adhesive force,
and water absorption properties of the tablets were determined to compare the
various PVAs. The highest values of the tensile strength and the in vitro
adhesive force were observed for PVAs with a medium viscosity and small particle
size. The optimal PVA was identified by a factorial design analysis. Mucoadhesive
tablets containing the optimal PVA were compared with carboxyvinyl polymer and
hydroxypropyl cellulose formulations. The optimal PVA gives a high adhesive
force, has a low viscosity, and resulted in relatively rapid drug release.
Formulations containing carboxyvinyl polymer had high tensile strengths but short
disintegration times. Higher hydroxypropyl cellulose concentration formulations
had good adhesion forces and very long disintegration times. We identified the
optimal characteristics of PVA, and the usefulness of mucoadhesive buccal tablets
containing this PVA was suggested from their formulation properties.
PMID- 28423954
TI - The design and scale-up of spray dried particle delivery systems.
AB - INTRODUCTION: The rising demand for pharmaceutical particles with tailored
physicochemical properties has opened new markets for spray drying especially for
solubility enhancement, improving inhalation medicines and stabilization of
biopharmaceuticals. Despite this, the spray drying literature is scattered and
often does not address the principles underpinning robust development of
pharmaceuticals. It is therefore necessary to present clearer picture of the
field and highlight the factors influencing particle design and scale-up. Areas
covered: The review presents a systematic analysis of the trends in development
of particle delivery systems using spray drying. This is followed by exploring
the mechanisms governing particle formation in the process stages. Particle
design factors including those of equipment configurations and feed/process
attributes were highlighted. Finally, the review summarises the current
industrial approaches for upscaling pharmaceutical spray drying. Expert opinion:
Spray drying provides the ability to design particles of the desired
functionality. This greatly benefits the pharmaceutical sector especially as
product specifications are becoming more encompassing and exacting. One of the
biggest barriers to product translation remains one of scale-up/scale-down. A
shift from trial and error approaches to model-based particle design helps to
enhance control over product properties. To this end, process innovations and
advanced manufacturing technologies are particularly welcomed.
PMID- 28423955
TI - Double ovarian stimulation (DuoStim) protocol for fertility preservation in
female oncology patients.
AB - This article describes a revised ovarian stimulation protocol (DuoStim) for
fertility preservation in female oncology patients which aims to maximise the
number of gametes obtained with subsequent improvement in cumulative birth rate,
without delaying cancer treatment. Ten patients diagnosed with malignancy between
September 2014 and October 2015 were included. The patients were treated with the
DuoStim protocol, undergoing two consecutive ovarian stimulation cycles and two
oocyte retrievals. The primary outcome was the number of oocytes collected and
vitrified during each oocyte retrieval and in total. The protocol was evaluated
regarding medical risk and patients' feedback. During the first oocyte collection
81 oocytes (61 metaphase II) were retrieved (mean = 8.1; range = 1-13) and during
the second oocyte collection 82 oocytes (67 metaphase II) were retrieved (mean=
8.2; range = 1-19). A total of 163 oocytes (128 metaphase II) were collected
(mean = 16.3; range = 6-32) and cancer treatment was not delayed for any of these
patients. There were no cases of ovarian hyperstimulation syndrome recorded. More
patients and long-term follow-up is needed to assess the efficacy and safety of
the DuoStim protocol. However, these early results are encouraging, demonstrating
an increase in number of mature oocytes retrieved during ovarian stimulation for
oncology patients, without delaying cancer treatment.
PMID- 28423956
TI - Statement of Retraction.
PMID- 28423957
TI - Trends in culprit drugs and clinical entities in cutaneous adverse drug
reactions: a retrospective study.
AB - PURPOSE: Morbidity due to cutaneous adverse drug reactions (CADRs) is quite
common. The specific culprit drugs change over time and clinicians must be kept
informed with updated knowledge, thus preventing potential CADRs. This
retrospective study is a survey of CADRs encountered in a hospital-based
population in Southern China during three time intervals, from 1984 to 2015.
MATERIALS AND METHODS: The clinical records were review of 306 patients with
CADRs who were admitted to our hospital from 2011 to 2015. These data were
compared with patients visiting our hospital during 1984-1994 and 2003-2010.
RESULTS: From 2011 to 2015, the most common CADRs were exanthematous reactions
(40.8%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; 17.0%).
There were eight cases (2.6%) of CADRs related to targeted therapy in oncology.
In the 205 CADR cases that were due to single medications, the most common
offending drugs were allopurinol (21.5%), cephalosporins (10.7%) and
carbamazepine (10.2%). The percentages of CADR cases due to allopurinol,
carbamazepine, or epidermal growth factor receptor inhibitors were significantly
higher from 2011 to 2015 compared with 1984-1994 or 2003-2010. The rate of
SJS/TEN occurrence was significantly higher in the two recent periods compared
with 1984-1994. CONCLUSIONS: Changes in drug prescriptions are a major factor
that affects the CADRs seen in clinical records. Newer drugs can be culpable for
CADRs, and more CADRs are now documented with increased severity at clinical
presentation. Reliable screening tests for specific drugs are urgently required
to eliminate possible fatalities.
PMID- 28423958
TI - Strategies and perspectives of assembling multi-enzyme systems.
AB - Multi-enzyme complexes have the potential to achieve high catalytic efficiency
for sequence reactions due to their advantages in eliminating product inhibition,
facilitating intermediate transfer and in situ regenerating cofactors.
Constructing functional multi-enzyme systems to mimic natural multi-enzyme
complexes is of great interest for multi-enzymatic biosynthesis and cell-free
synthetic biotransformation, but with many challenges. Currently, various
assembly strategies have been developed based on the interaction of
biomacromolecules such as DNA, peptide and scaffolding protein. On the other
hand, chemical-induced assembly is based on the affinity of enzymes with small
molecules including inhibitors, cofactors and metal ions has the advantage of
simplicity, site-to-site oriented structure control and economy. This review
summarizes advances and progresses employing these strategies. Furthermore,
challenges and perspectives in designing multi-enzyme systems are highlighted.
PMID- 28423959
TI - Diabetic pregnancy, maternal and fetal docosahexaenoic acid: a review of existing
evidence.
AB - OBJECTIVE: Docosahexaenoic acid (DHA) is vital for fetal development especially
during the third trimester of gestation when the speed of fetal brain growth is
at its peak. Diabetes modifies the maternal fatty acid profile, which may in turn
change the quantity and/or quality of lipids transferred to the fetus. Neonates
born to diabetic mothers might be more vulnerable to DHA deficiency leading to
lower cognitive scores together with lower overall intellectual quotients when
compared to control. We reviewed the influence of type 1 or type 2 pre
gestational (PGD) and gestational diabetes mellitus (GDM) on maternal and fetal
DHA levels. METHOD: We searched MEDLINE articles about PGD and/or GDM and DHA
published before October 2016. RESULTS: Maternal blood DHA level seems higher in
those with diabetes than those without diabetes. However, DHA in cord plasma of
neonates born to PGD and/or GDM mothers seem lower compared to neonates born to
nondiabetic mothers. CONCLUSIONS: Altogether, these results suggest that the
transfer of DHA from the mother to the fetus may be deficient or dysregulated in
diabetic pregnancies. What remains to be understood is how placental lipid
transport is regulated and whether there is a link with clinical
neurodevelopmental phenotypes in the newborns.
PMID- 28423960
TI - The role of molecular diagnostic testing in the management of thyroid nodules.
AB - INTRODUCTION: Fine needle aspiration (FNA) with cytologic examination remains the
standard of care for investigation of thyroid nodules. However, as many as 30% of
FNA samples are cytologically indeterminate for malignancy, which confounds
clinical management. To reduce the burden of repeat diagnostic testing and
unnecessary surgery, there has been extensive investigation into molecular
markers that can be detected on FNA specimens to more accurately stratify a
patient's risk of malignancy. Areas covered: In this review, the authors discuss
recent evidence and progress in molecular markers used in the diagnosis of
thyroid cancer highlighting somatic gene alterations, molecular technologies and
microRNA analysis. Expert commentary: The goal of molecular markers is to improve
diagnostic accuracy and aid clinicians in the preoperative management of thyroid
lesions. Modalities such as direct mutation analysis, mRNA gene expression
profiling, next-generation sequencing, and miRNA expression profiling have been
explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no
perfect test has been discovered, molecular diagnostic testing has revolutionized
the management of thyroid nodules.
PMID- 28423962
TI - The utility of fecal calprotectin in predicting the need for escalation of
therapy in inflammatory bowel disease.
AB - BACKGROUND AND AIMS: Fecal calprotectin is an important biomarker used in the
evaluation of inflammatory bowel disease. It has proven to be an effective tool
in initial screening as well monitoring response to therapy. The aim of this
study is to examine the utility of fecal calprotectin both as a predictor for the
escalation of therapy in established inflammatory bowel disease and as a
predictor of de novo diagnosis. METHODS: Patients with signs and symptoms
concerning for inflammatory bowel disease presenting to outpatient clinics were
recruited to provide fecal calprotectin stool samples prior to endoscopic
evaluation. Patients were followed up for at least one year and monitored
clinically for any change in symptomatology, escalation of therapy or development
of IBD, confirmed endoscopically. RESULTS: A total of 126 patients, of whom 72
were known to have underlying inflammatory bowel disease, were included in the
final analysis. Among the patients with elevated fecal calprotectin levels and
known inflammatory bowel disease, 66% (33/50) went on to have escalation of
therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels
were in the normal range (p < .0001). For the remaining patients who at baseline
did not have inflammatory bowel disease and a normal endoscopic evaluation,
elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the
next 12 months. CONCLUSIONS: Fecal calprotectin is a useful test for predicting
escalation of therapy in established inflammatory bowel disease.
PMID- 28423964
TI - Corrigendum.
PMID- 28423963
TI - Patient perceptions of environmental control units: experiences of Veterans with
spinal cord injuries and disorders receiving inpatient VA healthcare.
AB - PURPOSE: To assess patients' perceptions of environmental control units (ECUs) at
Veterans Affairs Spinal Cord Injury Centers. MATERIALS AND METHODS: A brief
questionnaire was conducted with patients in real-time while they were
hospitalised ("on-the-spot questionnaire"); a survey was mailed to patients who
had recently been discharged from a hospital stay ("discharge survey"). Data were
analysed using descriptive statistics. RESULTS: Seventy on-the-spot
questionnaires and 80 discharge surveys were collected. ECU features used most
frequently were comparable in responses from both surveys: watching TV/movies
(81%, 85%), calling the nurse (68%, 61%), turning lights on/off (63%, 52%),
adjusting the bed (53%, 33%), and playing games (39%, 24%). Many on-the-spot
questionnaire respondents felt the ECU met their need for independence a great
deal (42%). Most respondents to both surveys were satisfied with the ECU (71%,
57%). Areas for improvement included user training, improved functionality of the
device and its features, and device design. CONCLUSIONS: ECUs were well-accepted
by persons with spinal cord injuries/disorders (SCI/D) in the inpatient setting,
and increased patients' perceptions of independence. To maximise usability and
satisfaction, facilities should ensure that comprehensive training on ECU use and
features available is offered to all patients, and resources are available for
timely troubleshooting and maintenance. Implications for rehabilitation An
environmental control unit (ECU) is a form of assistive technology that allows
individuals with disabilities (such as spinal cord injuries and disorders
[SCI/D]) to control functional and entertainment-related aspects of their
environment. ECU use can increase functioning, independence and psychosocial well
being among individuals with SCI/D, by allowing users to reclaim control over day
to-day activities that are otherwise limited by their disability. Our study
results indicate that, among persons with SCI/D, ECUs are well-accepted and
increase perceptions of independence. To maximise usability and patient
satisfaction, facilities should ensure that comprehensive training on how to use
ECUs and what features are available is offered to all patients, and resources
are available for timely troubleshooting and maintenance.
PMID- 28423965
TI - Historical mitochondrial diversity in African leopards (Panthera pardus) revealed
by archival museum specimens.
AB - Once found throughout Africa and Eurasia, the leopard (Panthera pardus) was
recently uplisted from Near Threatened to Vulnerable by the International Union
for the Conservation of Nature (IUCN). Historically, more than 50% of the
leopard's global range occurred in continental Africa, yet sampling from this
part of the species' distribution is only sparsely represented in prior studies
examining patterns of genetic variation at the continental or global level. Broad
sampling to determine baseline patterns of genetic variation throughout the
leopard's historical distribution is important, as these measures are currently
used by the IUCN to direct conservation priorities and management plans. By
including data from 182 historical museum specimens, faecal samples from ongoing
field surveys, and published sequences representing sub-Saharan Africa, we
identify previously unrecognized genetic diversity in African leopards. Our mtDNA
data indicates high levels of divergence among regional populations and strongly
differentiated lineages in West Africa on par with recent studies of other large
vertebrates. We provide a reference benchmark of genetic diversity in African
leopards against which future monitoring can be compared. These findings
emphasize the utility of historical museum collections in understanding the
processes that shape present biodiversity. Additionally, we suggest future
research to clarify African leopard taxonomy and to differentiate between
delineated units requiring monitoring or conservation action.
PMID- 28423966
TI - Linear energy transfer distributions in the brainstem depending on tumour
location in intensity-modulated proton therapy of paediatric cancer.
AB - BACKGROUND: For tumours near organs at risk, there is concern about unintended
increase in biological dose from elevated linear energy transfer (LET) at the
distal end of treatment fields. The objective of this study was therefore to
investigate how different paediatric posterior fossa tumour locations impact LET
and biological dose to the brainstem during intensity-modulated proton therapy
(IMPT). MATERIAL AND METHODS: Multiple IMPT plans were generated for four
different simulated tumour locations relative to the brainstem for a five-year
old male patient. A prescribed dose of 59.4 Gy(RBE) was applied to the planning
target volumes (PTVs). Plans with two lateral and one posterior non-coplanar
fields were created, along with plans with modified field arrangements. The dose
averaged LET (LETd) and the physical dose * RBELET (D * RBELET), where RBELET=1+c
* LETd, were calculated using the FLUKA Monte Carlo code. A scaling parameter c
was applied to make the RBELET represent variations in the biological effect due
to LET. RESULTS: High LETd values surrounded parts of the PTV and encompassed
portions of the brainstem. Mean LETd values in the brainstem were 3.2-6.6
keV/MUm. The highest absolute brainstem LETd values were seen with the tumour
located most distant from the brainstem, whereas lower and more homogeneous LETd
values were seen when the tumour invaded the brainstem. In contrast, the highest
mean D * RBELET values were found in the latter case (54.0 Gy(RBE)), while the
case with largest distance between tumour and brainstem had a mean D * RBELET of
1.8 Gy(RBE). CONCLUSIONS: Using IMPT to treat posterior fossa tumours may result
in high LETd values within the brainstem, particularly if the tumour volume is
separated from the brainstem. However, the D * RBELET was greater for tumours
that approached or invaded the brainstem. Changing field angles showed a
reduction of LETd and D * RBELET in the brainstem.
PMID- 28423967
TI - Identifying selectively important amino acid positions associated with
alternative habitat environments in fish mitochondrial genomes.
AB - Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to
develop genetic adaptations to alternative environment factors, especially
salinity. Functional consequences of the protein variations associated with
habitat environments in fish mitochondrial genomes have not yet received much
attention. We analyzed 829 complete fish mitochondrial genomes and compared the
amino acid differences of 13 mitochondrial protein families between FW and SW
fish groups. We identified 47 specificity determining sites (SDS) that associated
with FW or SW environments from 12 mitochondrial protein families. Thirty-two
(68%) of the SDS sites are hydrophobic, 13 (28%) are neutral, and the remaining
sites are acidic or basic. Seven of those SDS from ND1, ND2 and ND5 were scored
as probably damaging to the protein structures. Furthermore, phylogenetic tree
based Bayes Empirical Bayes analysis also detected 63 positive sites associated
with alternative habitat environments across ten mtDNA proteins. These signatures
could be important for studying mitochondrial genetic variation relevant to fish
physiology and ecology.
PMID- 28423968
TI - Penetrating brain injury with a metal bar and a knife: Report of two interesting
cases.
AB - Introduction Penetrating brain injury (PBI) is uncommon among the civilian
population. Here, we report two interesting cases of PBI. Case presentation The
first patient was a 20-year-old male who sustained a penetrating head injury with
a metal bar during an accident at work. The patient underwent early surgical
intervention, and related meningitis was treated with antibiotics. The patient
was discharged 45 days later with no deficit. The second patient was a 34-year
old male who was the victim of a violence attack and was admitted to hospital. He
was struck by a knife to his right temporal bone. A brain computed tomography
scan and magnetic resonance imaging (MRI) demonstrated the tract of the knife
within the brain parenchyma. The patient underwent conservative treatment. After
several weeks, the patient was discharged in good health. Conclusion Although
severe PBI has a poorer prognosis than a blunt brain injury, in treating of these
patients, aggressive and timely surgical intervention, proper wide-spectrum
antibiotic administration, stringent and diligent care in the intensive-care unit
and careful management of the associated complications are mandated.
PMID- 28423970
TI - Recent advances on topical antimicrobials for skin and soft tissue infections and
their safety concerns.
AB - Antimicrobial resistance of disease-related microorganisms is considered a
worldwide prevalent and serious issue which increases the failure of treatment
outcomes and leads to high mortality. Considering that the increased resistance
to systemic antimicrobial therapy often needs of the use of more toxic agents,
topical antimicrobial therapy emerges as an attractive route for the treatment of
infectious diseases. The topical antimicrobial therapy is based on the absorption
of high drug doses in a readily accessible skin surface, resulting in a reduction
of microbial proliferation at infected skin sites. Topical antimicrobials retain
the following features: (a) they are able to escape the enzymatic degradation and
rapid clearance in the gastrointestinal tract or the first-pass metabolism during
oral administration; (b) alleviate the physical discomfort related to intravenous
injection; (c) reduce possible adverse effects and drug interactions of systemic
administrations; (d) increase patient compliance and convenience; and (e) reduce
the treatment costs. Novel antimicrobials for topical application have been
widely exploited to control the emergence of drug-resistant microorganisms. This
review provides a description of antimicrobial resistance, common microorganisms
causing skin and soft tissue infections, topical delivery route of
antimicrobials, safety concerns of topical antimicrobials, recent advances,
challenges and future prospective in topical antimicrobial development.
PMID- 28423969
TI - Process Evaluation of the Type 2 Diabetes Mellitus PULSE Program Randomized
Controlled Trial: Recruitment, Engagement, and Overall Satisfaction.
AB - BACKGROUND: Men are underrepresented in weight loss and type 2 diabetes mellitus
(T2DM) prevention studies. PURPOSE: To determine the effectiveness of
recruitment, and acceptability of the T2DM Prevention Using LifeStyle Education
(PULSE) Program-a gender-targeted, self-administered intervention for men.
METHODS: Men (18-65 years, high risk for T2DM) were randomized to intervention (
n = 53) or wait-list control groups ( n = 48). The 6-month PULSE Program
intervention focused on weight loss, diet, and exercise for T2DM prevention. A
process evaluation questionnaire was administered at 6 months to examine
recruitment and selection processes, and acceptability of the intervention's
delivery and content. Associations between self-monitoring and selected outcomes
were assessed using Spearman's rank correlation. RESULTS: A pragmatic recruitment
and online screening process was effective in identifying men at high risk of
T2DM (prediabetes prevalence 70%). Men reported the trial was appealing because
it targeted weight loss, T2DM prevention, and getting fit, and because it was
perceived as "doable" and tailored for men. The intervention was considered
acceptable, with men reporting high overall satisfaction (83%) and engagement
with the various components. Adherence to self-monitoring was poor, with only 13%
meeting requisite criteria. However, significant associations were observed
between weekly self-monitoring of weight and change in weight ( rs = -.47, p =
.004) and waist circumference ( rs = -.38, p = .026). Men reported they would
have preferred more intervention contact, for example, by phone or email.
CONCLUSIONS: Gender-targeted, self-administered lifestyle interventions are
feasible, appealing, and satisfying for men. Future studies should explore the
effects of additional non-face-to-face contact on motivation, accountability,
self-monitoring adherence, and program efficacy.
PMID- 28423971
TI - Intrauterine infection, immune system and premature birth.
AB - Preterm birth accounts for nearly one million deaths among children under five
years of age, and although its etiopathogenesis is not fully elucidated,
ascending intrauterine infection and fetal inflammatory response seem to be the
main triggers. The intense inflammatory response mediated by IL-1beta, TNF-alpha,
PAF, IFN-gamma and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage
and rupture, increased uterine contractions and biochemical and structural
changes in the cervix. Furthermore, preterm neonates have deficient innate and
adaptive immune responses characterized by reduced levels of IgG, opsonization
and phagocytosis, as well as increased activation of Th1 cells in relation to Th2
cells. Therefore, this triad is favors the occurrence of neonatal complications,
such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of
prematurity and bronchopulmonary dysplasia. Due to serious maternal and child
health complications of intrauterine infection, several studies have tried to
identify biomarkers for the early diagnosis of this entity. This literature
review aims to discuss the main scientific findings regarding the association
between ascending intrauterine infection, immune system and preterm birth.
PMID- 28423972
TI - Sexual Function and Testosterone Level in Men With Conservatively Treated Chronic
Kidney Disease.
AB - Sexual dysfunctions are common, but underrecognized, in patients with chronic
kidney disease (CKD) and are inversely associated with the glomerular filtration
rate (GFR). Sexual dysfunctions may affect quality of life in males with CKD. The
aim of this study was to analyze the relationship among sex hormones, sexual
function, and sexual satisfaction in a group of men between 18 and 50 years of
age with CKD Stages 1 to 5 not treated with hemodialysis or peritoneal dialysis.
Fasting blood samples for hemoglobin, testosterone, prolactin, and luteinizing
hormone and questionnaire surveys (Sexual Complaints Screener for Men,
International Index of Erectile Function, and Aging Male Symptom scale) were
evaluated in 100consecutive men. Higher CKD stage (i.e., lower renal function)
had a statistically significant ( p < .01) correlation with lower total
testosterone, free testosterone, and hemoglobin levels, and higher luteinizing
hormone and prolactin levels. Sexual function/dysfunctions were not significantly
associated with CKD stage, even after adjustment for age and serum testosterone.
The results indicate that CKD stage is a factor affecting testosterone levels in
combination with age in men between 18 and 50 years of age at different stages of
CKD but not treated with hemodialysis or peritoneal dialysis. Sexual dysfunctions
are common but not strongly correlated to testosterone levels, prolactin levels,
and survey (Sexual Complaints Screener for Men, International Index of Erectile
Function, and Aging Male Symptom scale) responses in patients with CKD.
PMID- 28423973
TI - Neurological involvement of IgG4-related disease: description of a case and
review of the literature.
AB - IgG4-related disease is a recently discovered pathological entity, histologically
characterised by fibrosis and IgG4-positive plasma cell infiltration. This
condition may virtually involve every site of the organism, with a various range
of clinical presentations. The most commonly affected organ is the pancreatic
gland, but it can also involve the biliary tract, salivary and lacrimal glands,
kidneys, orbital tissues, lymph nodes, lungs and many others. More recently, IgG4
related disease has been demonstrated to involve, in rare cases, also the central
nervous system, with a pattern mainly characterised by hypertrophic
pachymeningitis. In this paper we evaluated the clinical and magnetic resonance
imaging features of the IgG4-related disease in the central nervous system,
reporting a case of brain and spinal cord involvement. In our case, in fact, a 62
year-old man complaining of paresthesia, burning dysesthesia and severe
hyposthenia in the lower limbs presented with inflammatory pseudotumour with
orbital involvement and focal dural and spinal root thickening.
PMID- 28423974
TI - Competitive bass anglers: a new concern in sports medicine.
AB - OBJECTIVE: Competitive bass angling involves sport fishing against other anglers
while targeting a species of fish known as the black basses. Due to the rapidly
growing popularity of high school competitive bass angling in Alabama and the
nature of the casting motion similar to that of overhead athletes, we sought to
examine the prevalence of sports type injuries in this population. METHODS: In
spring 2016, an anonymous survey was distributed across two large scale
competitive high school fishing tournaments, allowing for a broad sampling of
anglers throughout the state of Alabama. Survey items included demographic
information, relevant past medical history, and various pains associated with the
shoulder, elbow and wrist. Results were recorded and analyzed electronically
using Microsoft Excel and IBM SPSS statistical software. RESULTS: A total of 257
surveys were recorded. The response rate was 61%. The mean age of participating
anglers was 15 +/- 1.61 years. The majority (42%) of anglers fished year round.
On average, anglers casted nearly 1,000 more times while competing versus fishing
recreationally. Approximately 15% of anglers experienced shoulder, elbow, and
wrist pain. The most common factors associated with pain included higher
tournament cast counts, number of competitive years, number of tournaments/year,
number of tournaments, and use of light weight lures. CONCLUSION: A large portion
of high school competitive anglers experience upper extremity pain. Knowledge of
angling factors associated with pain allow for the creation of a modifiable
routine to help reduce pain in affected anglers and prevent pain in healthy
anglers.
PMID- 28423976
TI - Screening for Dyslexia in French-Speaking University Students: An Evaluation of
the Detection Accuracy of the Alouette Test.
AB - Developmental dyslexia is a lifelong impairment affecting 5% to 10% of the
population. In French-speaking countries, although a number of standardized tests
for dyslexia in children are available, tools suitable to screen for dyslexia in
adults are lacking. In this study, we administered the Alouette reading test to a
normative sample of 164 French university students without dyslexia and a
validation sample of 83 students with dyslexia. The Alouette reading test is
designed to screen for dyslexia in children, since it taps skills that are
typically deficient in dyslexia (i.e., phonological skills). However, the test's
psychometric properties have not previously been available, and it is not
standardized for adults. The results showed that, on the Alouette test, dyslexic
readers were impaired on measures of accuracy, speed, and efficiency
(accuracy/reading time). We also found significant correlations between the
Alouette reading efficiency and phonological efficiency scores. Finally, in terms
of the Alouette test, speed-accuracy trade-offs were found in both groups, and
optimal cutoff scores were determined with receiver operator characteristic
curves analysis, yielding excellent discriminatory power, with 83.1% sensitivity
and 100% specificity for reading efficiency. Thus, this study supports the
Alouette test as a sensitive and specific screening tool for adults with
dyslexia.
PMID- 28423975
TI - Turning Points in the Lives of Youth of With/Without ADHD: Are They Linked to
Changes in Substance Use?
AB - OBJECTIVE: This study examines the behavior beliefs, social supports, and turning
points in individuals with/without ADHD related to their substance use/abuse
(SU/A) decisions. METHOD: The coded interviews from 60 participants with/without
ADHD were compared for their SU/A decisions and precipitants with these decisions
among abstainers, persisters, and desisters. RESULTS: ADHD participants reported
fewer social advantages to avoid SU/A than non-ADHD participants. Desisters and
persisters reported more social advantages of using drugs than abstainers.
Persisters reported both more negative and positive psychological/physiological
effects of SU/A. ADHD participants reported fewer positive role models in their
lives. Non-ADHD patients reported more positive turning points than ADHD
participants, regardless of SU/A status. CONCLUSION: ADHD individuals face
challenges in making healthy decisions about SU/A due to lack of positive role
models. Reinforcing accurate behavioral beliefs may be important to change
behaviors in individuals with SU/A or to prevent SU/A initiation in ADHD
individuals.
PMID- 28423977
TI - Age-associated differences in motor output variability and coordination during
the simultaneous dorsiflexion of both feet.
AB - Older adults are more variable than young adults on tasks that demand the
simultaneous control of more than one effector, and the difference between age
groups may be related to their different capacity of coordinating the force
output of the involved effectors. The goal of this study was to determine whether
age-associated differences in motor output variability during tasks involving the
simultaneous dorsiflexion of two feet can be partially explained by differences
in coordination and possibly attenuated by physical training. Ten young and 22
old adults (10 trained and 12 untrained old adults) volunteered to participate in
the study. Trained older adults had experience in a high-intensity mixed modality
training (MMT) regime for a minimum of 1 year. Volunteers performed successive
trials of a constant force task and a goal-directed task, with and without visual
feedback. Within- and between-trial variability were calculated and coordination
was quantified using the uncontrolled manifold (UCM) approach (i.e., co-variation
of the force outputs of both feet were used to quantify a motor synergy index).
Older adults exhibited greater variability and lower synergy (p < .05),
independently of physical training status, than young adults. Removal of visual
feedback caused greater variability and lower synergy for all groups (p < .05).
Our results suggest that older adults exhibit greater motor output variability in
tasks involving the simultaneous dorsiflexion of both feet possibly due to a lack
of coordination between the feet.
PMID- 28423978
TI - Reward Processing Deficits During a Spatial Attention Task in Patients With ADHD:
An fMRI Study.
AB - OBJECTIVE: In this study, we aimed to explore how cues signaling rewards and
feedbacks about rewards are processed in ADHD. METHOD: Inside the scanner, 16
healthy children and 19 children with ADHD completed a spatial attention paradigm
where cues informed about the availability of reward and feedbacks were provided
about the earned reward. RESULTS: In ventral anterior thalamus (VA), the controls
exhibited greater activation in response to reward-predicting cues, as compared
with no-reward cues, whereby in the ADHD group, the reverse pattern was observed
(nonreward > reward). For feedbacks; absence of rewards produced greater
activation than presence in the left caudate and frontal eye field for the
control group, whereas for the ADHD group, the reverse pattern was again observed
(reward > nonreward). DISCUSSION: The present findings indicate that ADHD is
associated with difficulty integrating reward contingency information with the
orienting and regulatory phases of attention.
PMID- 28423979
TI - Pregnancy-associated plasma protein-A truncation limits in antenatal screening
for trisomy 18.
AB - Upper and lower truncation limits are commonly applied to quantitative markers
used in medical screening tests. We here examine data on 375 trisomy 18 and
522,081 unaffected singleton pregnancies, to determine if the lower truncation
limit should be set below the previously specified 0.2 multiples of the median. A
lower truncation limit of 0.15 would reduce the underestimation of the risk of
having a trisomy 18 pregnancy in about 50% of affected pregnancies and would lead
to an estimated 10 percentage point increase in the detection rate, with only a
very small increase in the false-positive rate.
PMID- 28423980
TI - Multiple myeloma of the spine.
AB - Radiology provides a crucial clinical adjunct in patients with plasma cell
disorders, in particular multiple myeloma, and its uses are evolving and
expanding. This pictorial review illustrates the role of imaging throughout the
patient's clinical course, with specific reference to recently updated
international diagnostic criteria. At presentation, imaging optimises
characterisation and staging of the plasma-cell disorder, while later in the
course of the disease, its roles include the monitoring of disease progression,
assessment of post-treatment response and the investigation of clinical
deterioration.
PMID- 28423981
TI - Post-partum follow-up of women with gestational diabetes mellitus: effectiveness,
determinants, and barriers.
AB - BACKGROUND: Despite the recommendations for postpartum blood glucose monitoring
post gestational diabetes mellitus (GDM); scientific evidence reveals that these
recommendations may not be fully complied to. This study aimed to follow-up women
up to 2 years post-delivery with pregnancies complicated by GDM and healthy
controls to assess this fact. METHODS: Women with GDM (n = 78) and normal glucose
tolerant (n = 89) delivered in 2014 were followed up for 2 years. They were
informed and enquired via telephone about their blood glucose screening, physical
activity, postpartum complications, and current weight status of mother and baby.
RESULTS: Women with previous GDM were older and reported higher body weight 2
years post-delivery. At the 2 year follow-up, n = 11 (14.1%) participants had
developed diabetes, all with previous GDM. Both weight at birth (3.8 +/- 0.5 kg)
and at 2-year (10.7 +/- 2.3 kg) for the babies born to GDM mothers was
significantly higher than the NGT group babies (2.6 +/- 0.63 and 7.1 +/- 1.4 kg;
p < .05). Only 27 women regularly opted for T2DM screening via monitoring blood
glucose or HbA1c levels postpartum. The top reason for failed screening included:
believing that GDM would disappear after delivery, and being occupied with the
baby. CONCLUSIONS: The high incidence of T2DM in women with previous GDM is an
alarming finding. Given this trend, systematic follow-up programs are needed to
reduce obesity and diabetes risk.
PMID- 28423982
TI - From Data to Improved Decisions: Operations Research in Healthcare Delivery.
AB - BACKGROUND: The Operations Research Interest Group (ORIG) within the Society of
Medical Decision Making (SMDM) is a multidisciplinary interest group of
professionals that specializes in taking an analytical approach to medical
decision making and healthcare delivery. ORIG is interested in leveraging
mathematical methods associated with the field of Operations Research (OR) to
obtain data-driven solutions to complex healthcare problems and encourage
collaborations across disciplines. This paper introduces OR for the non-expert
and draws attention to opportunities where OR can be utilized to facilitate
solutions to healthcare problems. METHODS: Decision making is the process of
choosing between possible solutions to a problem with respect to certain metrics.
OR concepts can help systematically improve decision making through efficient
modeling techniques while accounting for relevant constraints. Depending on the
problem, methods that are part of OR (e.g., linear programming, Markov Decision
Processes) or methods that are derived from related fields (e.g., regression from
statistics) can be incorporated into the solution approach. This paper highlights
the characteristics of different OR methods that have been applied to healthcare
decision making and provides examples of emerging research opportunities.
EXAMPLES: We illustrate OR applications in healthcare using previous studies,
including diagnosis and treatment of diseases, organ transplants, and patient
flow decisions. Further, we provide a selection of emerging areas for utilizing
OR. CONCLUSIONS: There is a timely need to inform practitioners and policy makers
of the benefits of using OR techniques in solving healthcare problems. OR methods
can support the development of sustainable long-term solutions across disease
management, service delivery, and health policies by optimizing the performance
of system elements and analyzing their interaction while considering relevant
constraints.
PMID- 28423984
TI - Congenital amelanotic melanoma in a crossbred heifer calf.
AB - A large, pedunculated cutaneous mass protruding from the left flank fold and an
enlarged left prefemoral lymph node were found on examination of a 3-d-old
crossbred Aberdeen Angus heifer. The calf was asymptomatic aside from peripheral
lymphadenopathy, and the mass, along with the left prefemoral lymph node, was
surgically excised. Histologic examination of the mass and the lymph node
revealed a homogeneous population of neoplastic cells that stained positively
with immunohistochemical stains S100 and melan A, supporting a diagnosis of
congenital amelanotic melanoma with nodal metastasis. Two months later, the calf
became acutely recumbent and was euthanized after clinical examination revealed
widespread metastasis. Gross autopsy revealed widely disseminated metastases that
involved vertebral bodies, spinal cord, heart, kidneys, lungs, oral mucosa,
multiple lymph nodes, and the marrow cavity of several long bones. Our case
serves as a reminder that, although rare, congenital neoplasms occur in bovids
and have the potential for aggressive, metastatic behavior.
PMID- 28423985
TI - Anesthetic Approach for Endoscopic Repair of Acquired Tracheoesophageal Fistula.
AB - Tracheoesophageal fistula develops in 5 % to 15 % of patients with esophageal
cancer. Metal stent placement can be used for treatment. Stent placement can
result in aspiration, hemorrhage, perforation, migration, and pneumonia. Patients
may present for medical attention with unanticipated worsening of the fistula and
stent displacement requiring special anesthetic care. We discuss the
perianesthetic management of a patient with malignant tracheoesophageal fistula
and stent migration who presented for endoscopic esophageal stent replacement.
PMID- 28423986
TI - Global longitudinal strain from resting echocardiogram is associated with long
term adverse cardiac outcomes in patients with suspected coronary artery disease.
AB - PURPOSE: Measuring myocardial strain using two-dimensional speckle tracking
echocardiography has emerged as a new tool to identify subclinical ventricular
dysfunction. Abnormal strain has been shown to have superior sensitivity compared
with dobutamine stress echocardiography for viability assessment; however, there
is a paucity of data regarding the prediction of long-term major adverse cardiac
events. We compared the prognostic ability of both global longitudinal strain
(GLS) from resting echocardiograms to regional wall motion score index (WMSI)
from stress echocardiograms in their ability to predict long-term major adverse
cardiac events. METHODS: Patients referred for stress echocardiography, who also
underwent coronary angiography within 3 months of stress echo (n=122), were
enrolled. Patients with reduced ejection fractions (<40%) were excluded. Patients
were followed for a median of 3.4 years for major adverse cardiac events,
readmissions and repeat cardiac testing. RESULTS: Patients with abnormal GLS (GLS
<16.8%) from the resting echocardiogram obtained as part of the exercise
echocardiogram experienced a significantly shorter time to major adverse cardiac
events (p=0.026), first cardiovascular hospitalization and repeat cardiac testing
(p=0.0011) compared to those with normal GLS. Abnormal GLS appears to be a better
predictor than abnormal WMSI in predicting major adverse cardiac events (p=0.174)
and time to first cardiovascular hospitalization or repeat cardiac testing
(p=0.0093). CONCLUSION: GLS may be a better predictor of long-term major adverse
cardiac events, readmissions and repeat cardiac testing than WMSI in patients
undergoing stress echocardiography.
PMID- 28423987
TI - Reproducibility of upper leg EMG frequency content during cycling.
AB - Reproducibility of frequency content from surface electromyography (sEMG) signals
has not been assessed and it is unknown if incremental load testing design could
affect sEMG in cycling. The goals of this study were to assess the
reproducibility of measures from sEMG frequency content between sessions and to
compare these frequency components between a ramp and a step incremental cycling
test. Eighteen cyclists performed four incremental load cycling tests to
exhaustion. Two tests were performed using a step increment (load started at 100
W for 3 min followed by increments of 30 W every 3 min) and two were performed
using a ramp increment (load started at 100 W for 1 min followed by increments of
30 W.min-1). sEMG was monitored bilaterally for the rectus femoris and vastus
lateralis throughout the tests and converted into overall activation (whole
signal bandwidth), high- and low-frequency contents. The reproducibility of the
frequency content ranged from none to strong (ICC = 0.07-0.90). Vastus lateralis
activation was larger at the step compared to the ramp test (P < 0.01), without
differences for rectus femoris (P = 0.22-0.91) and for the high-frequency (P =
0.28-0.95) and low-frequency contents (P = 0.13-0.94). sEMG from vastus lateralis
and rectus femoris presented none to strong reproducibility. Vastus lateralis is
more activated in step test design.
PMID- 28423988
TI - Tumor collision of uterine adenocarcinoma and leiomyosarcoma in a goat.
AB - An aged mixed-breed goat doe was presented with a 9-mo history of serosanguineous
vaginal discharge. Vaginal speculum examination revealed serosanguineous
discharge but otherwise no abnormalities. Transrectal ultrasonography showed
normal ovaries and multifocal cystic lesions within the uterus.
Ovariohysterectomy was recommended because of a strong suspicion of neoplasia.
Multiple, non-resectable masses were noted in and around the uterus
intraoperatively, and euthanasia was elected. Autopsy revealed multiple masses
within the uterus, cervix, and lung parenchyma. Histologically, the masses within
the uterus represented a likely collision tumor of primary adenocarcinoma and
leiomyosarcoma. Our report highlights the importance of obtaining biopsy samples
of all masses because the lesions described showed significantly different
biological behavior. This information is vital to guide treatment and prognosis.
PMID- 28423989
TI - Outbreaks of bovine herpesvirus 2 infections in calves causing ear and facial
skin lesions.
AB - We describe 3 outbreaks of superficial dermatitis caused by bovine herpesvirus 2
(BoHV-2) in dairy breed calves. Clinically, all of the affected calves were 12-26
d of age, had alopecia and crusts on the face and ears, and were non-pruritic and
afebrile. Affected animals recovered spontaneously without any treatment within 2
4 wk after onset of clinical signs based on 1 herd with follow up. Histologic
examination of all skin crust or tissue samples identified neutrophilic
inflammation, mild hyperkeratosis, multinucleate syncytial cells, and
intranuclear inclusion bodies in the syncytial cells. Real-time PCR testing on
affected surface crusts or tissue provided evidence of BoHV-2, and testing, where
performed, was negative for parapoxvirus including bovine papular stomatitis
virus and the ovine form of malignant catarrhal fever tested in EDTA blood
samples. Bovine viral diarrhea virus also was negative by ELISA, as well as
bovine herpesvirus 1 by immunohistochemistry. Direct electron microscopy of
infected tissues in the first outbreak revealed herpesvirus-like particles.
PMID- 28423990
TI - Self-assembled nanogel of cholesterol-bearing xyloglucan as a drug delivery
nanocarrier.
AB - Xyloglucan (XG) is a multibranched polysaccharide consisting of a main chain beta
1,4-glucan with xylose and galactose side chains. In this study, cholesterol
bearing XG (CHXG) was synthesized by the reaction of XG with cholesteryl N-(6
isocyanatohexyl) carbamate. The CHXG molecules self-assembled in water to form
nanogels consisting of about 100 molecules of XG, and were characterized using
light scattering and transmission electron microscopy. The number of cholesteryl
groups per physical cross-linking site was estimated using a fluorescence
quenching method. The resulting CHXG nanogels could be complexed with molecules
of low molecular weight, such as iodine and paclitaxel, making the nanogels
useful as drug carriers. The CHXG nanogels could also be specifically
internalized by hepatocytes via the galactose receptors on their cell surface.
CHXG self-assembled nanogels may be suitable as novel drug nanocarriers with
galactose-specific targetability.
PMID- 28423991
TI - Changes in body mass, stature and BMI in South African elite U18 Rugby players
from different racial groups from 2002-2012.
AB - The purpose of this study was to determine whether there are differences between
racial groups for body mass, stature and body mass index (BMI) in South African
elite U18 rugby players and whether there were significant changes in these
measurements between 2002 and 2012. Self-reported body mass and stature were
obtained from U18 players (n = 4007) who attended the national tournament during
this period. BMI was calculated for each player.White players were 9.8 kg heavier
than black players, who were 2.3 kg heavier than coloured players (P < 0.0001).
The body mass of all groups increased from 2002 to 2012 (P < 0.0001). White
players were 7.0 cm taller than black players who were 0.5 cm taller than
coloured players (P < 0.0001). Players' stature measurements did not change
significantly during the study period. The average BMI of white players was 0.9
kg.m-2 greater than black players who were on average 0.7 kg.m-2 greater than
coloured players (P < 0.0001). The BMI of all groups changed similarly over the
study period. The body mass, stature and BMI of elite under-18 rugby players in
South Africa were significantly different between racial groups. This has
implications for transforming the game to make it representative of the South
African population.
PMID- 28423992
TI - Secrecy, empowerment and protection: positioning PrEP in KwaZulu-Natal, South
Africa.
AB - The release of World Health Organisation guidelines recommending the prophylactic
use of daily Truvada(r) for all populations at high risk of acquiring HIV opens
the way for implementation of oral pre-exposure prophylaxis (PrEP). The impact of
new prevention technologies is, however, dependent on demand creation strategies
such as user awareness, acceptability and access, which in turn are influenced by
sociocultural and gender norms. This study was conducted in three locations in
KwaZulu-Natal, urban, rural and peri-urban, with six participatory workshops.
Knowledge, desirable features of a product and demand positioning for PrEP were
assessed using a participatory action media research process which included art
based activities and group discussion using a semi-structured interview schedule.
The data were analysed using thematic analysis. The key themes that emerged in
relation to product adoption were: ability to maintain secrecy of product use;
the need for agency with personal choices around HIV prevention; and an increased
desire for HIV protection. Findings reaffirm the influence of user engagement in
understanding the sociocultural dynamics that influence demand creation for PrEP
adoption.
PMID- 28423993
TI - Lateralization of motor reactions and formation of behavioural tactics during
learning in the eight-arm radial maze in adolescent and adult rats.
AB - The problem of motor lateralization in ontogenesis is important for understanding
adaptation development. In our experiment adolescent (P28-P30) and adult (P120)
rats were trained in an eight-arm radial maze and their motor behaviour compared
during training. During learning, the adult rats typically started by moving
either left or right direction in the central arena in choosing the way in the
maze. The adult rats also developed behavioural tactics to enter maze arms at 45
degrees or 90 degrees relative to the previously visited arm. The adolescent
rats showed no directional preference and no clear behavioural tactics when
entering maze arms. Based on our findings, we propose that motor lateralization
increases the efficacy of food search and leads to the elaboration of behavioural
tactics. Data obtained may reflect the fact that motor behaviour specialization
develops gradually during ontogenesis and is helpful for adaptation to the
environment.
PMID- 28423994
TI - Seasonal variation in sports participation.
AB - This study explores indicators describing socio-demographics, sports
participation characteristics and motives which are associated with variation in
sports participation across seasons. Data were drawn from the German Socio
Economic Panel which contains detailed information on the sports behaviour of
adults in Germany. Overall, two different measures of seasonal variation are
developed and used as dependent variables in our regression models. The first
variable measures the coefficient of (seasonal) variation in sport-related energy
expenditure per week. The second variable measures whether activity drops below
the threshold as defined by the World Health Organization (WHO). Results suggest
that the organisational setting, the intensity and number of sports practised,
and the motive for participation are strongly correlated with the variation
measures used. For example, both, participation in a sports club and a commercial
facility, are associated with reduced seasonal variation and a significantly
higher probability of participating at a volume above the WHO threshold across
all seasons. These findings give some impetus for policymaking and the planning
of sports programmes as well as future research directions.
PMID- 28423995
TI - Harvesting nutrients from source-separated urine using powdered rice straw.
AB - As a principle of resource-oriented sanitation practice, urine should be
separated from the source and utilized for other purposes such as producing
fertilizer. This is because urine is rich in nutrients; therefore, sending it
directly to wastewater treatment plants causes problems in the regular treatment
process. The addition of solid additives such as powdered rice straw can help
with harvesting nutrients from urine. In this study, the procedure and efficiency
of using powdered rice straw for nutrient harvesting were investigated by
tracking the reductions in ammonia, phosphate, magnesium, and calcium ions, and
the harvested nutrients were identified using crystallography methods. Results
show that the ammonia, phosphate, and magnesium ions showed similar reduction
trends. However, the reduction process was limited by the magnesium and phosphate
availability, which reduced the nutrient harvesting efficiency. The nutrients
harvested with the rice straw were identified to be mostly struvite. Balancing
the phosphate and magnesium ions with ammonia is recommended to improve the
efficiency of nutrient harvesting. The treated powdered rice straw can serve as a
good solid fertilizer, while the remaining urine, which includes fewer nutrients,
can be utilized for irrigation or sent to wastewater treatment plants.
PMID- 28423996
TI - Assessing user acceptance towards automated and conventional sink use for hand
decontamination using the technology acceptance model.
AB - Hand hygiene (HH) prevents harmful contaminants spreading in settings including
domestic, health care and food handling. Strategies to improve HH range from
behavioural techniques through to automated sinks that ensure hand surface
cleaning. This study aimed to assess user experience and acceptance towards a new
automated sink, compared to a normal sink. An adapted version of the technology
acceptance model (TAM) assessed each mode of handwashing. A within-subjects
design enabled N = 46 participants to evaluate both sinks. Perceived Ease of Use
and Satisfaction of Use were significantly lower for the automated sink, compared
to the conventional sink (p < 0.005). Across the remaining TAM factors, there was
no significant difference. Participants suggested design features including jet
strength, water temperature and device affordance may improve HH technology. We
provide recommendations for future HH technology development to contribute a
positive user experience, relevant to technology developers, ergonomists and
those involved in HH across all sectors. Practitioner Summary: The need to
facilitate timely, effective hand hygiene to prevent illness has led to a rise in
automated handwashing systems across different contexts. User acceptance is a key
factor in system uptake. This paper applies the technology acceptance model as a
means to explore and optimise the design of such systems.
PMID- 28423997
TI - Do lipid microemboli induce acute kidney injury during cardiopulmonary bypass?
AB - BACKGROUND: Acute kidney injury (AKI) following cardiopulmonary bypass affects 5%
of patients, representing significant postoperative morbidity and mortality.
Animal models have shown an increased uptake of lipid microemboli (LME) into the
renal vasculature, potentially indicating ischaemic causation. This study tested
a new lipid filtration system (RemoweLL) against a conventional system with no
lipid-depleting capacity to determine the efficacy of the filtration system and
its effects on renal function. METHODS: Thirty consecutive patients underwent
coronary artery bypass graft surgery using either the RemoweLL filtration system
(15 patients) or a conventional cardiopulmonary bypass circuit (15 patients).
Renal function was assessed using cystatin C concentrations as a surrogate marker
of glomerular injury, as well as perioperative glomerular filtration rate (GFR)
and serum creatinine concentrations. Patients were defined as having acute renal
injury if there was an increase in absolute serum creatinine ?3 mg/dL (26.4
umol/L) or 1.5-fold increase from baseline as categorised using the AKIN
criteria. RESULTS: Postoperative differences in LME count between the two groups
were highly significant [p<0.001]. Analysis of peak cystatin C concentrations
showed significantly lower levels in the LME filtration group on the 2nd
postoperative morning [p=0.04]. Two-factor ANOVA revealed a trend towards
interaction, but this failed to reach significance [p=0.06]. There were no
differences throughout the study period in serum creatinine or GFR [p>0.05].
There were no differences in any of the serum or urinary electrolytes.
CONCLUSIONS: This study has shown a trend towards improved cystatin C removal
with LME filtration; with significantly lower peak concentrations, although no
further evidence of renoprotection could be demonstrated. Further research is
warranted to establish possible renal benefits of LME filtration in patients
undergoing cardiac surgery.
PMID- 28423998
TI - Preexisting lesions associated with complete diaphyseal fractures of the third
metacarpal bone in 12 Thoroughbred racehorses.
AB - We characterized features of complete diaphyseal fractures of third metacarpal
bones in Thoroughbred racehorses. Given that stress fractures are known to occur
in the third metacarpal bone, an additional aim was to determine if complete
fractures are associated with signs of a preexisting incomplete stress fracture.
Bilateral metacarpi from 12 Thoroughbred racehorses euthanized because of
complete unilateral metacarpal diaphyseal fracture were examined visually and
radiographically. Open, comminuted, transverse or short oblique fractures
occurred in the middle of the diaphysis or supracondylar region. Periosteal
surface discoloration and bone callus formation contiguous with the fracture line
were present in fractured bones. All contralateral intact metacarpi had gross
anatomic lesions, and 10 had radiographic abnormalities similar to those observed
on fractured metacarpi. Catastrophic metacarpal fractures occurred in racehorses
with bilateral evidence of preexisting bone injury.
PMID- 28423999
TI - Toe brachial index measured by automated device compared to duplex
ultrasonography for detecting peripheral arterial disease in older people.
AB - Introduction To investigate the diagnostic accuracy of an automated toe blood
pressure device for detecting peripheral arterial disease in older people.
Methods Ninety participants underwent toe and brachial blood pressure
measurements and colour duplex ultrasonography of the right lower limb.
Peripheral arterial disease was diagnosed if > 50% arterial obstruction was
identified in any lower limb vessel using colour duplex ultrasonography. A
receiver operating characteristic curve was analysed and the sensitivity and
specificity of commonly used toe brachial index and toe blood pressure values
were determined. Results The optimum toe brachial index threshold value for
diagnosing peripheral arterial disease was 0.72 (sensitivity 76.2%, specificity
75%). The area under the curve was 0.829 (95% CI 0.743 to 0.915, p < 0.0001)
suggesting fair diagnostic accuracy. A toe blood pressure of 70 mmHg was found to
have excellent specificity (97.92%) for detecting PAD but poor sensitivity
(42.86%). Conclusions The accuracy of automated toe blood pressure and TBI
measurements was determined to be good when using colour duplex ultrasound as the
reference standard for the non-invasive diagnosis of peripheral arterial disease.
Results should be interpreted in the context of all clinical signs and symptoms.
PMID- 28424000
TI - Heavy metals and PAHs in canned fish supplies on the Serbian market.
AB - The aim of this study was to determine the level of heavy metals and polycyclic
aromatic hydrocarbons (PAHs) in 57 samples of canned tuna, 25 samples of canned
sardines, and 16 samples of canned smoked sprouts, collected from supermarkets in
Serbia. Heavy metal levels (lead, cadmium, mercury, arsenic, iron, copper, and
zinc) were determined using an inductive coupled plasma mass spectrometry method.
Sixteen analysed PAHs were determined using a gas chromatography-mass
spectrometry method. The trace elements in canned fish were in the range (mg kg
1) of 0.01-0.28 for lead, 0.003-0.08 for cadmium, 0.007-0.64 for mercury, 0.17
3.73 for arsenic, 3.88-52.2 for iron, 0.2-5.95 for copper, and 1.35-44.5 for
zinc. Total PAH levels reached 17.67 ug kg-1 in canned tuna and 15.12 ug kg-1 in
sardines, whereas in smoked sprouts it amounted to 57.19 ug kg-1. Some of the
samples contained cadmium, arsenic, copper, and benzo(a)pyrene above the limits
as set by the European and Serbian legislation.
PMID- 28424001
TI - Corrigendum.
PMID- 28424002
TI - Enzyme-linked immunosorbent assays for coproantigen detection of Ancylostoma
caninum and Toxocara canis in dogs and Toxocara cati in cats.
AB - We report the development and field validation of 2 ELISAs for the detection of
Ancylostoma caninum or Toxocara canis coproantigens in the feces of dogs with
experimental and natural infections, and evidence of cross-reactivity with
respective feline counterparts. A. caninum-specific coproantigens were detected
in feces of experimentally infected dogs starting at 9 d post-infection (dpi),
whereas eggs were not seen until 23 dpi. T. canis-specific coproantigens were
detected in 3 of 5 experimentally infected dogs by 31 dpi, and 4 of the 5 animals
by 38 dpi. T. canis eggs were seen in feces of 4 of the 5 animals by 38 dpi. One
dog had delayed coproantigen detection and low egg output. Additionally, 817
canine and 183 feline fecal samples from naturally infected animals tested by
flotation were subjected to coproantigen ELISA testing. Of these 1,000 canine and
feline samples, 13 and 23 samples, respectively, were positive for "hookworm" or
"roundworm" eggs; 19 and 26 samples were ELISA positive, respectively. The T.
canis ELISA detected T. cati coproantigen in cat fecal samples. Discrepant ELISA
and flotation results were obtained for 16 hookworm- and 13 roundworm-positive
samples. Re-examination of the egg-positive, ELISA-negative samples indicated
several instances of possible misidentification or coprophagy, whereas detection
of antigen in samples without egg observations is likely a reflection of true
infection status with egg shedding below detection levels. There is good
indication, based on accumulated field data, that these antigen tests also detect
other hookworm and ascarid species.
PMID- 28424003
TI - Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by
Mutations in STT3A.
AB - STT3A encodes the catalytic subunit of the oligosaccharyltransferase complex. A
congenital disorder of glycosylation caused by mutations in STT3A has only been
reported in one family to date, associated with a Type I congenital disorder of
glycosylation pattern of transferrin glycoforms. The authors describe a further 5
related individuals with a likely pathogenic variant in STT3A, 2 of whom also had
variants in TUSC3. Common phenotypic features in all symptomatic individuals
include developmental delay, intellectual disability, with absent speech and
seizures. Two individuals also developed episodic hypothermia and altered
consciousness. The family were investigated by autozygosity mapping, which
revealed both a homozygous region containing STT3A and, in addition, a homozygous
deletion of TUSC3 in one child. A likely pathogenic variant in STT3A was
confirmed on Sanger sequencing of all affected individuals: the authors discuss
the molecular findings in detail and further delineate the clinical phenotype of
this rare disorder.
PMID- 28424004
TI - Segmental Diffusion Properties of the Corticospinal Tract and Motor Outcome in
Hemiparetic Children With Perinatal Stroke.
AB - Perinatal stroke injures developing motor systems, resulting in hemiparetic
cerebral palsy. Diffusion tensor imaging can explore structural connectivity. We
used diffusion tensor imaging to assess corticospinal tract diffusion in
hemiparetic children with perinatal stroke. Twenty-eight children (6-18 years)
with unilateral stroke underwent diffusion tensor imaging. Four corticospinal
tract assessments included full tract, partial tract, minitract and region of
interest. Diffusion characteristics (fractional anisotropy, mean, axial, and
radial diffusivity) were calculated. Ratios (lesioned/nonlesioned) were compared
across segments and to validated long-term motor outcomes (Pediatric Stroke
Outcome Measure, Assisting Hand Assessment, Melbourne Assessment). Fractional
anisotropy and radial diffusivity ratios decreased as tract size decreased, while
mean diffusivity showed consistent symmetry. Poor motor outcomes were associated
with lower fractional anisotropy in all segments and radial diffusivity
correlated with both Assisting Hand Assessment and Melbourne Assessment.
Diffusion imaging of segmented corticospinal tracts is feasible in hemiparetic
children with perinatal stroke. Correlations with disability support clinical
relevance and utility in model development for personalized rehabilitation.
PMID- 28424007
TI - Anesthetic-Related Neurotoxicity and Neuroimaging in Children: A Call for
Conversation.
AB - Each year millions of young children undergo procedures requiring sedation or
general anesthesia. An increasing proportion of the anesthetics used are provided
to optimize diagnostic imaging studies such as magnetic resonance imaging.
Concern regarding the neurotoxicity of sedatives and anesthetics has prompted the
US Food and Drug Administration to change labeling of anesthetics and sedative
agents warning against repeated or prolonged exposure in young children. This
review aims to summarize the risk of anesthesia in children with an emphasis on
anesthetic-related neurotoxicity, acknowledge the value of pediatric
neuroimaging, and address this call for conversation.
PMID- 28424008
TI - Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses.
AB - Olfactory axons project from nasal epithelium to the primitive telencephalon
before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ
but arrive via the rostral migratory stream. Synaptic glomeruli and concentric
laminar architecture are unlike other cortices. Fetal olfactory maturation of
neuronal differentiation, synaptogenesis, and myelination remains incomplete at
term and have a protracted course of postnatal development. The olfactory
ventricular recess involutes postnatally but dilates in congenital hydrocephalus.
Olfactory bulb, tract and epithelium are repositories of progenitor stem cells in
fetal and adult life. Diverse malformations of the olfactory bulb can be
diagnosed by clinical examination, imaging, and neuropathologically. Cellular
markers of neuronal differentiation and synaptogenesis demonstrate immaturity of
the olfactory system at birth, previously believed by histology alone to occur
early in fetal life. Immaturity does not preclude function.
PMID- 28424010
TI - Olfactory Development, Part 1: Function, From Fetal Perception to Adult Wine
Tasting.
AB - Discrimination of odorous molecules in amniotic fluid occur after 30 weeks'
gestation; fetuses exhibit differential responses to maternal diet. Olfactory
reflexes enable reliable neonatal testing. Olfactory bulbs can be demonstrated
reliably by MRI after 30 weeks' gestation, and their hypoplasia or aplasia also
documented by late prenatal and postnatal MRI. Olfactory axons project from nasal
epithelium to telencephalon before olfactory bulbs form. Fetal olfactory
maturation remains incomplete at term for neuronal differentiation,
synaptogenesis, myelination, and persistence of the transitory fetal ventricular
recess. Immaturity does not signify nonfunction. Olfaction is the only sensory
system without thalamic projection because of its own intrinsic thalamic
equivalent. Diverse malformations of the olfactory bulb can be diagnosed by
clinical examination, imaging, and neuropathology. Some epileptic auras might be
primarily generated in the olfactory bulb. Cranial nerve 1 should be tested in
all neonates and especially in patients with brain malformations,
endocrinopathies, chromosomopathies, and genetic/metabolic diseases.
PMID- 28424011
TI - Endovascular treatment evolution for pure intraorbital arteriovenous fistula:
Three case reports and literature review.
AB - Background and importance Intraorbital arteriovenous fistulas (IOAVFs) are rare
and cause eye redness, exophthalmos, blurry vision and bruit. Whereas in the past
they were treated conservatively, surgically or transarterially, recent
developments in transvenous embolization have improved their treatment. In this
paper the authors report three cases of IOAVFs treated endovascularly and review
the evolution of treatment options. Methods Three cases of purely IOAVF enrolled
in our center were reported and a PubMed literature search was performed using
"pure intraorbital arteriovenous fistula" and "arteriovenous fistula of the optic
nerve sheath." A total of 21 papers were reviewed in full, focusing primarily on
the treatment and outcomes. Results A total of 26 patients were obtained,
including our three patients and 23 patients reported in the literature. In nine
patients treated conservatively, four spontaneous occlusions, one visual
deterioration and four cases with unknown outcome were reported. In another 18
patients, 29 therapies (including five surgical treatment, 11 transarterial
embolizations and 13 transvenous embolizations) were attempted and resulted in 12
cures, five visual deteriorations and one without reported outcome. More
recently, transvenous embolization has become the mainstay of IOAVF treatment. Of
the 21 patients assessed between 2000 and 2013, a transvenous approach was
attempted in 13 patients; nine patients were cured without any adverse events.
Conclusion Development and improvement of transvenous techniques are found to be
safe and effective for patients with IOAVF.
PMID- 28424012
TI - Internal carotid artery agenesis: A case report and review of literature.
AB - Congenital agenesis of the internal carotid artery is a very rare anomaly.
Intracranial circulation in the involved internal carotid artery territory is
maintained by collateral circulation from the contralateral internal carotid
artery through the anterior communicating artery and from the vertebrobasilar
system through the posterior communicating artery. Usually, patients with
internal carotid artery agenesis are asymptomatic due to collateral circulation,
but they may present with headache, seizures, or transient ischemic attack.
Aneurysms have also been reported to be associated with this entity. Computed
tomography angiography, magnetic resonance angiography, and digital subtraction
angiography are commonly used modalities to make the diagnosis. Unenhanced skull
base computed tomography will show the absence of carotid canal, thus
differentiating from carotid hypoplasia. We report on a case of right internal
carotid artery agenesis with discussion of embryogenesis, clinical presentation,
and imaging findings.
PMID- 28424013
TI - Anterior spinal artery aneurysm in aortic stenosis of different etiology: Report
of three cases.
AB - Isolated aneurysms of spinal arteries are rare. Spinal artery aneurysms are
commonly found in association with spinal cord arteriovenous malformation and
coarctation of aorta and rarely with aortic arch interruption and Klippel
Trenaunay syndrome. Spinal angiograms are the gold standard for diagnosing these
spinal artery aneurysms but with the advances in computed tomography technology
these aneurysms can also be very well demonstrated in computed tomography
angiograms. We describe three cases of anterior spinal artery aneurysm, those are
flow related aneurysms, associated with coarctation of aorta and with Takayasu
arteritis.
PMID- 28424014
TI - Semi-quantitative analysis of cerebral FDG-PET reveals striatal hypermetabolism
and normal cortical metabolism in a case of VGKCC limbic encephalitis.
AB - In the context of delayed autoimmune encephalitis antibody results, functional
imaging can support the diagnosis of limbic encephalitis associated with anti
voltage-gated potassium channel complex (VGKCC) antibodies. Here we present a
typical case of VGKCC encephalitis in a 69-year-old woman whose symptoms
responded to plasmapheresis. A cerebral 18F-fluoro-2-deoxy-d-glucose positron
emission tomography (FDG-PET) scan performed prior to commencing treatment
revealed striatal hypermetabolism assessed qualitatively and semi-quantitatively,
with normal uptake in the cortex and cerebellum when analysed semi
quantitatively. Repeat FDG-PET imaging performed three months later revealed
normalisation of striatal hypermetabolism. Previous case reports have described
striatal hypermetabolism and/or cortical hypometabolism in patients with VGKCC
encephalitis. However, most of these descriptions were based on qualitative
analyses only and may represent the relative change in cortical metabolism
compared with striatal metabolism. We recommend semi-quantitative analysis of
cerebral FDG-PET, in addition to reporting the qualitative FDG-PET images.
PMID- 28424015
TI - Susceptibility weighted imaging in acute cerebral ischemia: review of emerging
technical concepts and clinical applications.
AB - Susceptibility weighted imaging (SWI) is an essential magnetic resonance imaging
sequence in the assessment of acute ischemic stroke. In this article, we discuss
the physics principals and clinical application of conventional SWI and multi
echo SWI sequences. We review the research evidence and practical approach of SWI
in acute ischemic stroke by focusing on the detection and characterization of
thromboembolism in the cerebral circulation. In addition, we discuss the role of
SWI in the assessment of neuroparenchyma by depiction of asymmetric hypointense
cortical veins in the ischemic territory (surrogate tissue perfusion), detection
of existing microbleeds before stroke treatment and monitoring for hemorrhagic
transformation post-treatment. In conclusion, the SWI sequence complements other
parameters in the stroke magnetic resonance imaging protocol and understanding of
the research evidence is vital for practising stroke neurologists and
neuroradiologists.
PMID- 28424016
TI - Acute brain injury following illicit drug abuse in adolescent and young adult
patients: spectrum of neuroimaging findings.
AB - The use of illicit drugs is currently a major medical problem among adolescents.
Several illicit drugs have a high abuse potential and can be neurotoxic causing
high morbidity and mortality. The clinical manifestation of adolescents with
acute drug-induced neurotoxicity is often characterized by non-specific symptoms
and findings. Early diagnosis is important to prevent death and permanent long
term neurological impairments. We report on clinical and neuroimaging findings in
five adolescents with acute brain imaging following illicit drug intoxication to
highlight the role of neuroimaging findings in the diagnostic work-up of
pediatric acute drug-induced neurotoxicity. Our patients reveal two main
neuroimaging patterns of brain injury: diffuse symmetric subcortical white matter
injury with preferential cerebellar involvement (leukoencephalopathy pattern) or
multiple foci of ischemic infarctions in a non-arterial territory distribution
(ischemic pattern). Familiarity with these two neuroimaging patterns of findings
in the evaluation of magnetic resonance imaging studies in adolescents with
acutely altered mental status may suggest the correct diagnosis, narrow the
differential diagnosis, and consequently allow early initiation of targeted
laboratory investigations and treatment, potentially improving outcome.
PMID- 28424017
TI - Computed tomography perfusion-based selection of endovascularly treated acute
ischaemic stroke patients - Are there lessons to be learned from the pre-evidence
era?
AB - Introduction Some of the latest groundbreaking trials suggest that noncontrast
cranial computed tomography and computed tomography-angiography are sufficient
tools for patient selection within six hours of symptom onset. Before
endovascular stroke therapy became the standard of care, patient selection was
one of the most useful tools to avoid futile reperfusions. We report the outcomes
of endovascularly treated stroke patients selected with a perfusion-based
paradigm and discuss the implications in the current era of endovascular
treatment. Material and methods After an interdisciplinary meeting in September
2012 we agreed to select thrombectomy candidates primarily based on computed
tomography perfusion with a cerebral blood volume Alberta Stroke Program Early
Computed Tomography Scale (CBV-ASPECTS) of <7 being a strong indicator of futile
reperfusion. In this study, we retrospectively screened all patients with an M1
thrombosis in our neurointerventional database between September 2012 and
December 2014. Results In 39 patients with a mean age of 69 years and a median
admission National Institute of Health Stroke Scale of 17 the successful
reperfusion rate was 74% and the favourable outcome rate at 90 days was 56%.
Compared to previously published data from our database 2007-2011, we found that
a two-point increase in median CBV-ASPECTS was associated with a significant
increase in favourable outcomes. Conclusion Computed tomography perfusion imaging
as an additional selection criterion significantly increased the rate of
favourable clinical outcome in patients treated with mechanical thrombectomy.
Although computed tomography perfusion has lost impact within the six-hour
period, we still use it in cases beyond six hours as a means to broaden the
therapeutic window.
PMID- 28424018
TI - Correction to: Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI)
in rats: identification of urinary metabolites.
PMID- 28424019
TI - Primary trauma care: a 20-year review.
AB - This year marks the 20th anniversary of the Primary Trauma Care Foundation (PTC),
which provides a course aimed at providing a systematic approach to trauma and
the unwell patient in low- and middle-income countries. The course is based on
the original 36-page PTC manual and a key ethos of being appropriate to the
target audience, affordable to those who need it, adaptable to the needs of each
local area and sustainable to perpetuate itself. The concept is simple: a two-day
course for candidates, followed by a one-day instructor course, and finally a
first course delivered to local healthcare staff by the first cohort. Now in its
20th year, its reach spans 76 countries, is ingrained in the syllabus of many
healthcare systems and continues to reach new territories with a programme shown
to produce a measurable improvement in the care delivered.
PMID- 28424020
TI - The utility of an obesity-specific small for gestational age standard for
pregnancies complicated by maternal obesity.
AB - INTRODUCTION: An obesity-specific standard for small for gestational age (SGA)
pregnancies may help identify additional at risk pregnancies. METHODS: This was a
retrospective cohort study of all non-anomalous singleton neonates born in Texas
from 2006-2011. Analysis was limited to births between 34 and 42 weeks gestation.
Two SGA birth weight standards (birth weight <=10th centile) were generated, one
using the entire population (SGApop) and another using obese pregnancies
(SGAcust). The outcomes of interest included: risks of stillbirth, neonatal
death, 5-minute Apgar score below 7, NICU admission, and assisted ventilation >6
h. RESULTS: Using the population standard, the prevalence of SGA complicated by
obesity was 8.1%, compared with 10.3% using the obesity-specific standard. 10,457
additional pregnancies were identified as SGA. Compared to obese AGA pregnancies,
the aHR for stillbirth was 5.45 [4.28, 6.94] for SGApop, and 1.21 [0.54, 2.74]
for SGAcust-pop. The risks for the following neonatal complications were slightly
higher for SGAcust-pop group compared to AGA group: neonatal death aOR 1.40
[1.05, 1.87], low 5-minute Apgar 1.31 [1.09, 1.57], and NICU admission 1.13
[1.03, 1.25]. These risks were lower than SGApop. CONCLUSIONS: Using an obesity
specific SGA standard, a subgroup of pregnancies with marginally increased risk
for neonatal complications was identified.
PMID- 28424021
TI - Air in intravenous lines: a need to review old opinions.
PMID- 28424022
TI - Analytical validation of an automated assay for ferric-reducing ability of plasma
in dog serum.
AB - We performed analytical validation of an automated ferric-reducing ability of
plasma (FRAP) assay in the serum of dogs. Intra- and interassay precision,
accuracy, detection limit, and effects of hemolysis and lipemia were evaluated.
Intra- and interassay coefficients of variation were <1% and <13%, respectively.
The assay showed a high correlation with a FRAP assay described previously, and
results were linear when serial sample dilutions were tested. The detection limit
was lower than the values observed in sera from healthy dogs; decreased serum
FRAP was found in dogs with leishmaniosis. Lipemia and hemolysis caused a
significant increase in the results of the assay.
PMID- 28424023
TI - Erratum.
PMID- 28424024
TI - Molecular profiling and bioactive potential of an endophytic fungus Aspergillus
sulphureus isolated from Sida acuta: a medicinal plant.
AB - CONTEXT: Sida acuta Burm.f. (Malvaceae) extracts are reported to have
applications against malaria, diuretic, antipyretic, nervous and urinary
diseases. No fungal endophytes of S. acuta are reported. OBJECTIVE: Isolation,
identification and evaluation of antibacterial, antioxidant, anticancer and
haemolytic potential of fungal endophytes from the ethnomedcinal plant S. acuta.
MATERIALS AND METHODS: Sida acuta stem segments were placed on PDA medium to
isolate endophytic fungi. The fungus was identified by genomic DNA analysis and
phylogenetic tree was constructed using ITS sequences (GenBank) to confirm
species. The antibacterial efficacy of Aspergillus sulphureus MME12 ethyl acetate
extract was tested against Gram-positive and Gram-negative pathogenic bacteria.
DPPH free radical scavenging activity, anticancer and DNA fragmentation against
EAC cells, and direct haemolytic activity (100-500 MUg/mL) using human
erythrocytes were determined. RESULTS AND DISCUSSION: The ethyl acetate extract
of A. sulphureus (Fresen.) Wehmer (Trichocomaceae) demonstrated significant
antibacterial potential against Staphylococcus aureus, Bacillus subtilis,
Escherichia coli and Salmonella typhi compared to streptomycin. MIC against test
pathogens was in the range of 15.6-62.5 MUg/mL. The antioxidant results revealed
significant RSA from 12.43% to 62.02% (IC50 = 350.4 MUg/mL, p <= 0.05). MME12
offered considerable inhibition of EAC proliferation (23% to 84%, IC50 = 216.7
MUg/mL, p <= 0.05) supported by DNA fragmentation studies. The extract also
offered insignificant haemolysis (5.6%) compared to Triton X-100. CONCLUSIONS: A
single endophytic fungus, A. sulphureus MME12 was isolated and identified using
molecular profiling. The above-mentioned findings support the pharmacological
application of A. sulphureus MME12 extract and demand for purification of the
active principle(s).
PMID- 28424025
TI - Selective reminding of prospective memory in Multiple Sclerosis.
AB - OBJECTIVE: Multiple sclerosis (MS) is associated with prospective memory (PM)
deficits, which may increase the risk of poor functional/health outcomes such as
medication non-adherence. This study examined the potential benefits of selective
reminding to enhance PM functioning in persons with MS. METHOD: Twenty-one
participants with MS and 22 healthy adults (HA) underwent a neuropsychological
battery including a Selective Reminding PM (SRPM) experimental procedure.
Participants were randomly assigned to either: (1) a selective reminding
condition in which participants learn (to criterion) eight prospective memory
tasks in a Selective Reminding format; or (2) a single trial encoding condition
(1T). RESULTS: A significant interaction was demonstrated, with MS participants
receiving greater benefit than HAs from the SR procedure in terms of PM
performance. Across diagnostic groups, participants in the SR conditions (vs. 1T
conditions) demonstrated significantly better PM performance. Individuals with MS
were impaired relative to HAs in the 1T condition, but performance was
statistically comparable in the SR condition. CONCLUSIONS: This preliminary study
suggests that selective reminding can be used to enhance PM cue detection and
retrieval in MS. The extent to which selective reminding of PM is effective in
naturalistic settings and for health-related behaviours in MS remains to be
determined.
PMID- 28424026
TI - Walking ability following Hybrid Assistive Limb treatment for a patient with
chronic myelopathy after surgery for cervical ossification of the posterior
longitudinal ligament.
AB - CONTEXT: The hybrid assistive limb (HAL) (the wearable robot) can assist kinesis
during voluntary control of hip and knee joint motion by detecting the wearer's
bioelectric signals on the surface of their skin. The purpose of this study was
to report on walking ability following the wearable robot treatment in a patient
with chronic myelopathy after surgery for cervical ossification of the posterior
longitudinal ligament (OPLL). FINDINGS: The patient was a 66-year-old woman with
cervical OPLL who was able to ambulate independently with the aid of bilateral
crutches. The wearable robot treatment was received once every 2 weeks for ten
sessions beginning approximately 14 years after surgery. Improvements were
observed in gait speed (BL 22.5; post 46.7 m/min), step length (BL 0.36; post
0.57 m), and cadence (BL 61.9; post 81.6 m/min) based on a 10-m walk test and a 2
minute walk test (BL 63.4; post 103.7 m) assessing total walking distance. The
improvements in walking ability were maintained after the wearable robot
treatment for 6 months. CONCLUSION: We report the functional recovery in the
walking ability of a patient with chronic cervical myelopathy following the
wearable robot treatment, suggesting that as a rehabilitation tool, the wearable
robot has the potential to effectively improve functional ambulation in chronic
cervical myelopathy patients whose walking ability has plateaued, even many years
after surgery.
PMID- 28424027
TI - The value of European exchange programs for early career family doctors.
AB - The Hippokrates Exchange programme (HEP) is designed to give early career General
Practitioners (Associates in Training (AITs)/First5s) first-hand experience into
concepts of a primary healthcare system outside of their host country. The aim is
to improve GP knowledge and skills, inspire professional development and promote
a global approach to primary care. Although an increasing number are taking up
this opportunity, their views and experiences of international exchanges are not
well described. The aim of the study was to explore the experiences of
AITs/First5s following their HEP exchanges. This qualitative study analysed 16
post-exchange reports of UK participants visiting 10 European countries via the
HEP, using a thematic approach. Participants were unanimously positive about
their exchange experiences. The themes that emerged were (1) Comparison of
primary care practice (2) Infrastructure of host primary care (3) Motivation and
experience of exchanges and (4) Learning and reflection. Participants displayed
considerable benefits from these exchanges by broadening their experience in
different primary care systems and identifying improvements to be incorporated
into their UK practice.
PMID- 28424028
TI - Church-Based Recruitment to Reach Korean Immigrants: An Integrative Review.
AB - Although the Korean church has been frequently used to recruit Korean immigrants
in research, little is known about the specific strategies and process. The
purpose of this integrative review was to describe recruitment strategies in
studies of Korean immigrants and to identify the process of Korean church-based
recruitment. Thirty-three studies met inclusion criteria. Four stages of church
based recruitment were identified: initiation, endorsement, advertisement, and
implementation. This review identified aspects of the church-based recruitment
process in Korean immigrants, which are different from the Black and Hispanic
literature, due to their hierarchical culture and language barriers. Getting
permission from pastors and announcing the study by pastors at Sunday services
were identified as the key components of the process. Using the church newsletter
to advertise the study was the most effective strategy for the advertisement
stage. Despite several limitations, church-based recruitment is a very feasible
and effective way to recruit Korean immigrants.
PMID- 28424029
TI - Baseline executive control ability and its relationship to language therapy
improvements in post-stroke aphasia: a systematic review.
AB - PURPOSE: To review current evidence on the relationship between executive control
(EC) and post-treatment language gains in adults with post-stroke aphasia.
METHOD: Electronic databases (CINAHL, Cochrane Trials, Embase, MEDLINE, MEDLINE
in-Process and PsycINFO) were systematically searched (year 2000 - present).
Abstracts and full-text articles were reviewed by two independent raters against
pre-specified criteria: original research with N > 2; at least 90% adults with
stroke, all undergoing treatment for acquired aphasia; pre-treatment EC abilities
were compared to language gains post-treatment across studies. Critical appraisal
was conducted using the Cochrane group and Single-Case Experimental Design (SCED)
methods. Data were extracted and summarised descriptively. RESULTS: Search
results yielded 2272 unique citations; ultimately 15 studies were accepted for
review. Both pre-treatment EC and language abilities appear to be important
indicators of treatment success, especially in moderate-severe aphasia. This
relationship emerged when EC was measured using specific (e.g., divided
attention), as opposed to broad (e.g., reasoning) tasks, and primarily when
naming therapy was administered; intensive constraint-induced therapy did not
correlate with treatment success. CONCLUSIONS: EC is a promising prognostic
variable regarding language recovery, but further research is required using a
priori declared theoretical EC models, along with properly powered samples,
standardised EC tasks and treatment protocols.
PMID- 28424030
TI - Expanded dengue syndrome: three concomitant uncommon presentations in the same
patient.
AB - We report a case of expanded dengue syndrome, where three uncommon presentations
occurred concomitantly. A patient with dengue haemorrhagic fever presented
initially with acute acalculous cholecystitis along with acute pancreatitis, but
later on, during resolution of pancreatitis and cholecystitis, developed
pancytopenia, most likely due to haemophagocytic syndrome. Such presentations,
besides being rare themselves, have not been reported to occur concomitantly, in
the same patient, during the same disease process.
PMID- 28424032
TI - The onslaught of infectious disease.
PMID- 28424031
TI - Yellow fever from Angola and Congo: a storm gathers.
AB - In common with Zika, Chikungunya and Dengue, Yellow Fever (YF) is an arthropod
borne flavivirus. It is transmitted between humans and from monkeys by mosquitoes
of the Aedes aegypti (its principal vector), haemogogus and albopictus varieties.
Three cycles of transmission may occur: urban; sylvatic; and intermediate.
Recently, sub-Saharan Africa has seen the resurgence of this neglected disease.
The current YF outbreak in Angola began in December 2015 in the capital Luanda
and by October 2016 there had been > 4300 suspected cases, with 376 deaths (case
fatality rate = 8.8%). A total of 884 were laboratory confirmed but it is likely
that case numbers may be seriously underestimated. YF has subsequently quickly
spread to neighbouring Congo and further afield to Kenya and also China, this
being of grave concern as this was a first introduction of YF to Asia. YF has
recently hit Brazil, with 555 suspected cases and 107 deaths reported by the end
of January 2017. Extremely rapid unplanned urban migration in Africa by non
immune rural populations to already densely populated cities, where high
densities of mosquitoes co-exist with city dwellers in makeshift flimsy
accommodation, poses a ready recipe for an epidemic of massive proportion. In
such conditions, with enormously strained public services existing among the most
needy and vulnerable populations, mosquito control programmes are nearly
impossible. YF in Congo is a tempest barely restrained. However, it is one that
can be controlled by focused and committed international collaboration, by
intense and united political will and by the marriage of old and trusted
techniques: a vaccine almost a century old and some of the most modern
technologies available to man.
PMID- 28424033
TI - A MELAS phenotype is not necessarily MELAS.
PMID- 28424034
TI - Clinical and laboratory factors associated with mortality in dengue.
AB - Dengue is endemic in more than 100 countries, giving rise to an increased number
of deaths in the last five years in the South-East Asian region. We report our
findings from a retrospective study of adults admitted with confirmed dengue at
our institution. We studied the clinical and laboratory parameters associated
with mortality in these patients. Of the 172 hospitalised patients studied, 156
(90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered
sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum
creatinine, higher serum transaminase and lower serum albumin levels to be
significantly associated with mortality in dengue. Further, using stepwise
multivariate logistic regression, altered sensorium ( P = 0.006) and
hypoalbuminemia ( P = 0.013) were identified as independent predictors of
mortality in dengue. Identification of these parameters early in the course of
disease should prompt intensification of treatment in dengue cases.
PMID- 28424035
TI - Coexistence of tuberculosis and malignancy: a mere coincidence or a causal
association.
AB - Tuberculosis (TB) and malignancy are among the most important current global
health problems. Many authors suggest that their coexistence is a chance
association owing to their high prevalence. There is, however, enough evidence
that one condition may predispose the other. In our retrospective report of two
cases, TB in draining lymph nodes was discovered incidentally on histopathology,
following surgical resection for malignancy. The possibility of coexistent
lesions, especially in regions endemic for TB, mandate a detailed
histopathological examination to prevent the chances of diagnostic failure and
thus therapeutic error.
PMID- 28424037
TI - Aortic Customized Stent-Graft Treatment of Postnephrectomy Renal Pedicle
Arteriovenous Fistula.
AB - A postnephrectomy renal acquired arteriovenous fistula (AVF) is a rare clinical
entity that may cause high-output heart failure. Most of the cases are identified
time along after surgery. We present a case of a postnephrectomy renal AVF
treated with aortic customized stent-graft.
PMID- 28424038
TI - A Novel Method for the Treatment of Bilateral Hypogastric Aneurysms Using Hybrid
Polytetrafluoroethylene Graft.
AB - Open aortic aneurysm repair in the setting of bilateral hypogastric aneurysms is
technically challenging. We present a novel technique for open surgical repair
for bilateral hypogastric aneurysms using the Gore hybrid vascular graft (GVHG;
W. L. Gore and Associates Inc, Flagstaff, Arizona). The GVHG is an expanded
polytetrafluoroethylene graft with a nitinol stent at 1 end designed for
hemodialysis access. The GVHG has been also been used for aortic debranching and
treatment of occlusive disease. We describe the first report using GVHG to repair
hypogastric aneurysms.
PMID- 28424039
TI - Endovascular Treatment of Ischemic Stroke: An Updated Meta-Analysis of Efficacy
and Safety.
AB - BACKGROUND: Recent randomized trials demonstrated the superiority of the
mechanical thrombectomy over the best medical treatment in patients with acute
ischemic stroke due to an occlusion of arteries of proximal anterior circulation.
In this updated meta-analysis, we aimed to summarize the total clinical effects
of the treatment, including the last trials. METHODS: We performed literature
search of Randomized Crontrolled Trials (RCTs) published between 2010 and October
2016, comparing endovenous thrombolysis plus mechanical thrombectomy
(intervention group) with best medical care alone (control group). We identified
8 trials. Primary outcomes were reduced disability at 90 days from the event and
symptomatic intracranial hemorrhage. Statistical analysis was performed pooling
data into the 2 groups, evaluating outcome heterogeneity. The Mantel-Haenszel
method was used to calculate odds ratios (ORs). RESULTS: We analyzed data for
1845 patients (interventional group: 911; control group: 934). Mechanical
thrombectomy contributed to a significant reduction in disability rate compared
to the best medical treatment alone (OR: 2.087; 95% confidence interval [CI]:
1.718-2.535; P < .001). We calculated that for every 100 treated patients, 16
more participants have a good outcome as a result of mechanical treatment. No
significant differences between groups were observed concerning the occurrence of
symptomatic hemorrhage (OR: 1.021; 95% CI: 0.641-1.629; P = .739). CONCLUSION:
Mechanical thrombectomy contributes to significantly increase the functional
benefit of endovenous thrombolysis in patients with acute ischemic stroke caused
by arterial occlusion of proximal anterior circulation, without reduction in
safety. These findings are relevant for the optimization of the acute stroke
management, including the implementation of networks between stroke centers.
PMID- 28424040
TI - Challenges of Takayasu Arteritis in Pregnancy: A Case Report.
AB - Takayasu arteritis is a rare, chronic vasculitis of unknown etiology
characterized by inflammation of the aorta and its main branches. Although
Takayasu arteritis mostly affects women of childbearing age, there is a paucity
in the literature on pregnancy associated with Takayasu arteritis. Pregnant
patients are at increased risk of cardiovascular complications, including
hypertension and congestive heart failure, which may jeopardize both maternal and
fetal outcomes. Furthermore, optimal management has not yet been established for
pregnant patients with Takayasu arteritis, posing a clinical challenge. We
present a case of a young woman with Takayasu arteritis whose symptoms and
disease activity improved during 2 pregnancies. Although her first pregnancy was
complicated with preeclampsia, gestational diabetes, and preterm vaginal
delivery, her second pregnancy was uneventful. This case provides a rare glimpse
of Takayasu arteritis in pregnancy and highlights the challenges of medical
management in gravid patients.
PMID- 28424041
TI - Endovascular Treatment of Massive Axillary Artery Aneurysm for Palliation.
AB - Atherosclerotic axillary artery aneurysms are rare. We report a case of a ninety
six year old female who presented with a pulsatile left breast mass causing her
intractable pain. She was diagnosed with a massive axillary artery aneurysm which
was treated with and endovascular aneurysm repair for palliation of her symptoms.
PMID- 28424042
TI - The Effect of a New Angiographic Imaging Technology on Radiation Dose in Visceral
Embolization Procedures.
AB - PURPOSE: To evaluate the impact of a new angiographic imaging technology on
radiation dose during visceral embolization procedures involving both fluoroscopy
and digital subtraction angiography. MATERIAL AND METHODS: A retrospective
analysis from a single-center consecutive series of patients was performed
comparing 2 angiographic imaging systems. The AlluraClarity (CIQ; Philips
Healthcare, Best, the Netherlands) was used in 100 patients (n = 59 male, mean
age: 70.6 years) from July 2013 to April 2014 and compared to the former
AlluraXper (AX) technology used in 139 patients (n = 71 male, mean age: 70.1
years) from May 2011 to June 2013. Patients were categorized according to body
mass index (BMI [kg/m2])-group 1: BMI <25, group 2: BMI >=25 and <30, and group
3: BMI >=30. Fluoroscopy time, the total dose of iodinated contrast administered,
and procedural AirKerma (Ka, r [mGy]) were obtained. RESULTS: Mean BMI was 26.4
+/- 5.0 kg/m2 in the CIQ and 26.4 +/- 7.1 kg/m2 in the AX group ( P = .93).
Fluoroscopy time and the amount of contrast media were equally distributed. Ka, r
was 1342.9 mGy versus 2214.8 mGy ( P < .001, t test) when comparing CIQ to AX.
Comparing CIQ to AX, BMI subgroup analysis revealed a mean Ka, r of 970.1 to
1586.1 mGy ( P = .003, t test), 1484.7 to 2170.1 mGy ( P = .02, t test), and
1848.8 to 3348.9 mGy ( P = .001, t test) in BMI groups 1, 2, and 3, respectively.
CONCLUSION: The CIQ technology significantly reduced mean radiation dose by 39.4%
for visceral embolization procedures when compared to fluoroscopy time and
contrast media dose. This dose relationship was consistent across all BMI groups.
PMID- 28424043
TI - Nutcracker Syndrome: Case Report on the Management of Recurrent Stenosis After
Stenting.
AB - Nutcracker syndrome is a clinical entity leading to renal venous hypertension due
to extrinsic compression of the left renal vein by the superior mesenteric
artery. Current surgical therapy involves placement of an oversized renal vein
stent with partial protrusion into the inferior vena cava (IVC) to relieve
stenosis and prevent stent migration. Here, we present a patient with intractable
pain and hematuria secondary to nutcracker syndrome who underwent left renal vein
stent placement and developed recurrent symptoms due to flow-limiting kinking at
the left renal hilum, with partial obstruction of the IVC from pseudointimal
hyperplasia. This was treated with stent excision and construction of a left
neorenal vein bypass. Thus, given these complications, we should perhaps revisit
the recommendations for oversizing of the stent.
PMID- 28424044
TI - Emergent Carotid Thromboendarterectomy for Acute Symptomatic Occlusion of the
Extracranial Internal Carotid Artery.
AB - BACKGROUND: Strokes secondary to acute internal carotid artery (ICA) occlusion
are associated with an extremely poor prognosis. The best treatment approach in
this setting is still unknown. The aim of our study was to evaluate the efficacy,
safety, and outcomes of emergent surgical revascularization of acute extracranial
ICA occlusion in patients with minor to severe ischemic stroke. METHODS: A
retrospective analysis was performed using prospectively collected data of
consecutive patients who underwent carotid thromboendarterectomy for symptomatic
acute ICA occlusion during the period from January 2013 to December 2015. Primary
outcomes were disability at 90 days assessed by the modified Rankin Scale (mRS)
and neurological deficit at discharge assessed using the National Institute of
Health Stroke Scale (NIHSS). Secondary outcomes were the recanalization rate, 30
day overall mortality, and any intracerebral bleeding. RESULTS: During the study
period, a total of 6 patients (5 men and 1 woman) with a median age of 64 years
(range: 58-84 years) underwent emergent reconstruction for acute symptomatic ICA
occlusion within a median of 5.4 hours (range: 2.9-12.0 hours) after symptoms
onset. The median presenting NIHSS score was 10.5 points (range: 4-21). Before
surgery, 4 patients (66.7%) had been treated by systemic recombinant tissue
plasminogen activator lysis. The median time interval between initiation of
intravenous thrombolysis and carotid thromboendarterectomy was 117.5 minutes
(range: 65-140 minutes). Patency of the ICA was achieved in all patients. On
discharge, the median NIHSS score was 2 points (range: 0-11 points). There was no
postoperative intracerebral hemorrhage and zero 30-day mortality rate. At 3
months, 5 patients (83.3%) had a good clinical outcome (mRS <= 2). CONCLUSION:
Patients presenting with minor to severe ischemic stroke syndromes due to
isolated extracranial ICA occlusion may benefit from emergent carotid
revascularization. Thorough preoperative neuroimaging is essential to aid in
selecting eligible candidates for acute surgical intervention.
PMID- 28424045
TI - A modified Mediterranean dietary intervention for adults with major depression:
Dietary protocol and feasibility data from the SMILES trial.
AB - BACKGROUND: The SMILES trial was the first randomized controlled trial (RCT)
explicitly designed to evaluate a dietary intervention, conducted by qualified
dietitians, for reducing depressive symptomatology in adults with clinical
depression. OBJECTIVES: Here we detail the development of the prescribed diet
(modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive
disorders (MDDs) that was designed specifically for the SMILES trial. We also
present data demonstrating the extent to which this intervention achieved
improvements in diet quality. METHODS: The ModiMedDiet was designed using a
combination of existing dietary guidelines and scientific evidence from the
emerging field of nutritional psychiatric epidemiology. Sixty-seven community
dwelling individuals (Melbourne, Australia) aged 18 years or over, with current
poor quality diets, and MDDs were enrolled into the SMILES trial. A retention
rate of 93.9 and 73.5% was observed for the dietary intervention and social
support control group, respectively. The dietary intervention (ModiMedDiet)
consisted of seven individual nutrition counselling sessions delivered by a
qualified dietitian. The control condition comprised a social support protocol
matched to the same visit schedule and length. RESULTS: This manuscript details
the first prescriptive individualized dietary intervention delivered by
dietitians for adults with major depression. Significant improvements in dietary
quality were observed among individuals randomized to the ModiMedDiet group.
These dietary improvements were also found to be associated with changes in
depressive symptoms. DISCUSSION/CONCLUSION: The ModiMedDiet, a novel and
individually tailored intervention designed specifically for adults with major
depression, can be effectively implemented in clinical practice to manage this
highly prevalent and debilitating condition. TRIAL REGISTRATION: Australia and
New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered 29
February 2012.
PMID- 28424046
TI - Perspectives of policy-makers and stakeholders about health care waste management
in community-based care in South Africa: a qualitative study.
AB - BACKGROUND: In South Africa, a new primary health care (PHC) re-engineering
initiative aims to scale up the provision of community-based care (CBC). A
central element in this initiative is the use of outreach teams comprising nurses
and community health workers to provide care to the largely poor and marginalised
communities across the country. The provision of care will inevitably lead to an
increase in the amount of health care waste (HCW) generated in homes and suggests
the need to pay more attention to the HCW that emanates from homes where there is
care of a patient. CBC in South Africa is guided by the home-based care policy.
However, this policy does not deal with issues about how HCW should be managed in
CBC. This study sought to explore health care waste management (HCWM) in CBC in
South Africa from the policy-makers' and stakeholders' perspective. METHODS: Semi
structured interviews were conducted with 9 policy-makers and 21 stakeholders
working in 29 communities in Durban, South Africa. Interviews were conducted in
English; were guided by an interview guide with open-ended questions. Data was
analysed thematically. RESULTS: The Durban Solid waste (DSW) unit of the
eThekwini municipality is responsible for overseeing all waste management
programmes in communities. Lack of segregation of waste and illegal dumping of
waste were the main barriers to proper management practices of HCW at household
level while at the municipal level, corrupt tender processes and inadequate
funding for waste management programmes were identified as the main barriers. In
order to address these issues, all the policy-makers and stakeholders have taken
steps to collaborate and develop education awareness programmes. They also liaise
with various government offices to provide resources aimed at waste management
programmes. CONCLUSIONS: HCW is generated in CBC and it is poorly managed and
treated as domestic waste. With the rollout of the new primary health care model,
there is a greater need to consider HCWM in CBC. There is need for the Department
of Health to work together with the municipality to ensure that they devise
measures that will help to deal with improper HCWM in the communities.
PMID- 28424047
TI - Deciphering mechanisms underlying the genetic variation of general production and
liver quality traits in the overfed mule duck by pQTL analyses.
AB - BACKGROUND: The aim of this study was to analyse the mechanisms that underlie
phenotypic quantitative trait loci (QTL) in overfed mule ducks by identifying co
localized proteomic QTL (pQTL). The QTL design consisted of three families of
common ducks that were progeny-tested by using 294 male mule ducks. This
population of common ducks was genotyped using a genetic map that included 334
genetic markers located across 28 APL chromosomes (APL for Anas platyrhynchos).
Mule ducks were phenotyped for 49 traits related to growth, metabolism,
overfeeding ability and meat and fatty liver quality, and 326 soluble fatty liver
proteins were quantified. RESULTS: One hundred and seventy-six pQTL and 80
phenotypic QTL were detected at the 5% chromosome-wide significance threshold.
The great majority of the identified pQTL were trans-acting and localized on a
chromosome other than that carrying the coding gene. The most significant pQTL
(1% genome-wide significance) were found for alpha-enolase on APL18 and fatty
acid synthase on APL24. Some proteins were associated with numerous pQTL (for
example, 17 and 14 pQTL were detected for alpha-enolase and apolipoprotein A1,
respectively) and pQTL hotspots were observed on some chromosomes (APL18, 24, 25
and 29). We detected 66 co-localized phenotypic QTL and pQTL for which the
significance of the two-trait QTL (2t-QTL) analysis was higher than that of the
strongest QTL using a single-trait approach. Among these, 16 2t-QTL were
pleiotropic. For example, on APL15, melting rate and abundance of two alpha
enolase spots appeared to be impacted by a single locus that is involved in the
glycolytic process. On APLZ, we identified a pleiotropic QTL that modified both
the blood level of glucose at the beginning of the force-feeding period and the
concentration of glutamate dehydrogenase, which, in humans, is involved in
increased glucose absorption by the liver when the glutamate dehydrogenase 1 gene
is mutated. CONCLUSIONS: We identified pleiotropic loci that affect metabolic
pathways linked to glycolysis or lipogenesis, and in the end to fatty liver
quality. Further investigation, via transcriptomics and metabolomics approaches,
is required to confirm the biomarkers that were found to impact the genetic
variability of these phenotypic traits.
PMID- 28424048
TI - Phylogeny, divergence time and historical biogeography of Laetiporus
(Basidiomycota, Polyporales).
AB - BACKGROUND: The aim of this study was to characterize the molecular relationship,
origin and historical biogeography of the species in important brown rot fungal
genus Laetiporus from East Asia, Europe, Pan-America, Hawaii and South Africa. We
used six genetic markers to estimate a genus-level phylogeny including (1) the
internal transcribed spacer (ITS), (2) nuclear large subunit rDNA (nrLSU), (3)
nuclear small subunit rDNA (nrSSU), (4) translation elongation factor 1-alpha (EF
1alpha), (5) DNA-directed RNA polymerase II subunit 2 (RPB2), and (6)
mitochondrial small subunit rDNA (mtSSU). RESULTS: Results of multi-locus
phylogenetic analyses show clade support for at least seventeen species-level
lineages including two new Laetiporus in China. Molecular dating using BEAST
estimated the present crown group diverged approximately 20.16 million years ago
(Mya) in the early Miocene. Biogeographic analyses using RASP indicated that
Laetiporus most likely originated in temperate zones with East Asia and North
America having the highest probability (48%) of being the ancestral area.
CONCLUSIONS: Four intercontinental dispersal routes and a possible concealed
dispersal route were established for the first time.
PMID- 28424049
TI - Findings in young adults at colonoscopy from a hospital service database audit.
AB - BACKGROUND: Colorectal cancer (CRC) diagnosed at <50 years is predominantly
located in the distal colon and rectum. Little is known about which lesion
subtypes may serve as CRC precursors in young adults. The aim of this work was to
document the prevalence and histological subtype of lesions seen in patients aged
<50 years, and any associated clinical features. METHODS: An audit of the
colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia
over a 12-month period was undertaken. Findings were recorded from both
colonoscopy reports and corresponding histological examination of excised
lesions. RESULTS: Data were extracted from colonoscopies in 2064 patients. Those
aged <50 comprised 485 (24%) of the total. CRC precursor lesions (including
sessile serrated adenoma/polyps (SSA/P), traditional serrated adenomas, tubular
adenomas >=10 mm or with high-grade dysplasia, and conventional adenomas with
villous histology) were seen in 4.3% of patients aged <50 and 12.9% of patients
aged >=50 (P <0.001). Among colonoscopies yielding CRC precursor lesions in
patients under 50 years, SSA/P occurred in 52% of procedures (11/21), compared
with 27% (55/204) of procedures in patients aged 50 and older (P = 0.02). SSA/P
were proximally located in (10/11) 90% of patients aged under 50, and 80% (43/54)
of those aged 50 and older (P = 0.46). CONCLUSIONS: SSA/P were the most
frequently observed CRC precursor lesions in patients aged <50. Most CRCs in this
age group are known to arise in the distal colon and rectum suggesting that
lesions other than SSA/P may serve as the precursor for the majority of early
onset CRC.
PMID- 28424050
TI - In the quest for degenerative lumbar spinal stenosis etiology: the Schmorl's
nodes model.
AB - BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) is a common health problem
in the elderly and usually associated with three-joint complex degeneration.
Schmorl's nodes (SNs) are described as vertical herniation of the disc into the
vertebral body through a weakened part of the end plate that can lead to disc
degeneration. Since SNs can harm the spine unit stability, the association
between DLSS and SNs is expected. The aim of this study is to shed light on the
relationship between degenerative lumbar spinal stenosis and SNs. METHODS: Two
groups of individuals were studied: the first included 165 individuals with DLSS
(age range: 40-88, sex ratio: 80 M/85 F) and the second 180 individuals without
spinal stenosis related symptoms (age range: 40-99, sex ratio: 90 M/90 F). The
presence or absence of SNs on the cranial and caudal end plate surfaces at the
lumbosacral region (from L1 to S1 vertebra) was recorded, using CT images
(Brilliance 64 Philips Medical System, Cleveland Ohio, thickness of the sections
was 1-3 mm and MAS, 80-250). Chi-Square test was taken to compare the prevalence
of SNs between the study groups (control and stenosis) by lumbar disc level, for
each gender separately. Multivariable logistic regression analysis was also used
to determine the association between DLSS and SNs. RESULTS: The prevalence rate
of SNs was significantly greater in the stenosis males (L1-2 to L5-S1) and
females (L4-5 and L4-S1) compared to their counterparts in the control (P <
0.001). In addition, the presence of SNs in both males and females was found to
increase the likelihood for DLSS. CONCLUSIONS: Our results indicate that SNs
prevalence is significantly greater in the DLSS group compared to the control.
Furthermore, SNs are strongly associated with DLSS.
PMID- 28424051
TI - Erratum to: Population seroprevalence of antibody to influenza A(H7N9) virus,
Guangzhou, China.
PMID- 28424052
TI - Using implementation facilitation to foster clinical practice quality and
adherence to evidence in challenged settings: a qualitative study.
AB - BACKGROUND: We evaluated a facilitation strategy to help clinical sites likely to
experience challenges implement evidence-based Primary Care-Mental Health
Integration (PC-MHI) care models within the context of a Department of Veterans
Affairs (VA) initiative. This article describes our assessment of whether
implementation facilitation (IF) can foster development of high quality PC-MHI
programs that adhere to evidence, are sustainable and likely to improve clinical
practices and outcomes. METHODS: Utilizing a matched pair design, we conducted a
qualitative descriptive evaluation of the IF strategy in sixteen VA primary care
clinics. To assess program quality and adherence to evidence, we conducted one
hour structured telephone interviews, at two time points, with clinicians and
leaders who knew the most about the clinics' programs. We then created structured
summaries of the interviews that VA national PC-MHI experts utilized to rate the
programs on four dimensions (overall quality, adherence to evidence,
sustainability and level of improvement). RESULTS: At first assessment, seven of
eight IF sites and four of eight comparison sites had implemented a PC-MHI
program. Our qualitative assessment suggested that experts rated IF sites'
programs higher than comparison sites' programs with one exception. At final
assessment, all eight IF but only five comparison sites had implemented a PC-MHI
program. Again, experts rated IF sites' programs higher than their matched
comparison sites with one exception. Over time, all ratings improved in five of
seven IF sites and two of three comparison sites. CONCLUSIONS: Implementing
complex evidence-based programs, particularly in settings that lack
infrastructure, resources and support for such efforts, is challenging. Findings
suggest that a blend of external expert and internal regional facilitation
strategies that implementation scientists have developed and tested can improve
PC-MHI program uptake, quality and adherence to evidence in primary care clinics
with these challenges. However, not all sites showed these improvements. To be
successful, facilitators likely need at least a moderate level of leaders'
support, including provision of basic resources. Additionally, we found that IF
and strength of leadership structure may have a synergistic effect on ability to
implement higher quality and evidence-based programs.
PMID- 28424053
TI - Stress induced nuclear granules form in response to accumulation of misfolded
proteins in Caenorhabditis elegans.
AB - BACKGROUND: Environmental stress can affect the viability or fecundity of an
organism. Environmental stressors may affect the genome or the proteome and can
cause cellular distress by contributing to protein damage or misfolding. This
study examines the cellular response to environmental stress in the germline of
the nematode, C. elegans. RESULTS: Salt stress, oxidative stress, and starvation,
but not heat shock, induce the relocalization of ubiquitin, proteasome, and the
TIAR-2 protein into distinct subnuclear regions referred to as stress induced
nuclear granules (SINGs). The SINGs form within 1 h of stress initiation and do
not require intertissue signaling. K48-linked polyubiquitin chains but not K63
chains are enriched in SINGs. Worms with a mutation in the conjugating enzyme,
ubc-18, do not form SINGs. Additionally, knockdown of ubc-20 and ubc-22 reduces
the level of SING formation as does knockdown of the ubiquitin ligase chn-1, a
CHIP homolog. The nuclear import machinery is required for SING formation.
Stressed embryos containing SINGs fail to hatch and cell division in these
embryos is halted. The formation of SINGs can be prevented by pre-exposure to a
brief period of heat shock before stress exposure. Heat shock inhibition of SINGs
is dependent upon the HSF-1 transcription factor. CONCLUSIONS: The heat shock
results suggest that chaperone expression can prevent SING formation and that the
accumulation of damaged or misfolded proteins is a necessary precursor to SING
formation. Thus, SINGs may be part of a novel protein quality control system. The
data suggest an interesting model where SINGs represent sites of localized
protein degradation for nuclear or cytosolic proteins. Thus, the physiological
impacts of environmental stress may begin at the cellular level with the
formation of stress induced nuclear granules.
PMID- 28424054
TI - An unusual delusion of duplication in a patient affected by Dementia with Lewy
bodies.
AB - BACKGROUND: Dementia with Lewy bodies (DLB) is the second most frequent diagnosis
of progressive degenerative dementia in older people. Delusions are common
features in DLB and, among them, Capgras syndrome represents the most frequent
disturbance, characterized by the recurrent and transient belief that a familiar
person, often a close family member or caregiver, has been replaced by an
identical-looking imposter. However, other delusional conditions near to
misidentification syndromes can occur in DLB patients and may represent a major
psychiatric disorder, although rarely studied systematically. CASE PRESENTATION:
We reported on a female patient affected by DLB who presented with an unusual
delusion of duplication. Referring to the female professional caregiver engaged
by her relatives for her care, the patient constantly described the presence of
two different female persons, with a disorder framed in the context of a delusion
of duplication. A brain 99Tc-hexamethylpropyleneamineoxime SPECT was performed
showing moderate hypoperfusion in both occipital lobes, and associated with
marked decreased perfusion in parieto-fronto-temporal lobes bilaterally.
CONCLUSIONS: An occipital hypoperfusion was identified, although in association
with a marked global decrease of perfusion in the remaining lobes. The role of
posterior lobes is certainly important in all misidentification syndromes where a
natural dissociation between recognition and identification is present. Moreover,
the concomitant presence of severe attentional and executive deficits evocative
for a frontal syndrome and the marked global decrease of perfusion in the
remaining lobes at the SPECT scan also suggest a possible dysfunction in an
abnormal connectivity between anterior and posterior areas.
PMID- 28424055
TI - How participation in surgical mortality audit impacts surgical practice.
AB - BACKGROUND: Surgical mortality audit is an important tool for quality assurance
and professional development but little is known about the impact of such
activity on professional practice at the individual surgeon level. This paper
reports the findings of a survey conducted with a self-selected cohort of
surgeons in Queensland, Australia, on their experience of participating in the
audit and its impact on their professional practice, as well as implications for
hospital systems. METHODS: The study used a descriptive cross-sectional survey
design. All surgeons registered in Queensland in 2015 (n = 919) were invited to
complete an anonymous online questionnaire between September and October 2015.
184 surgeons completed and returned the questionnaire at a response rate of 20%.
RESULTS: Thirty-nine percent of the participants reported that involvement in the
audit process affected their clinical practice. This was particularly the case
for surgeons whose participation included being an assessor. Thirteen percent of
the participants had perceived improvement to hospital practices or advancement
in patient care and safety as a result of audit recommendations. Analysis of the
open-ended responses suggested the audit experience had led surgeons to become
more cautious, reflective in action and with increased confidence in best
practice, and recognise the importance of effective communication and clear
documentation. CONCLUSIONS: This is the first study to examine the impact of
participation in a mortality audit process on the professional practice of
surgeons. The findings offer evidence for surgical mortality audit as an
effective strategy for continuous professional development and for improving
patient safety initiatives.
PMID- 28424056
TI - Use of multi-trait and random regression models to identify genetic variation in
tolerance to porcine reproductive and respiratory syndrome virus.
AB - BACKGROUND: A host can adopt two response strategies to infection: resistance
(reduce pathogen load) and tolerance (minimize impact of infection on
performance). Both strategies may be under genetic control and could thus be
targeted for genetic improvement. Although there is evidence that supports a
genetic basis for resistance to porcine reproductive and respiratory syndrome
(PRRS), it is not known whether pigs also differ genetically in tolerance. We
determined to what extent pigs that have been shown to vary genetically in
resistance to PRRS also exhibit genetic variation in tolerance. Multi-trait
linear mixed models and random regression sire models were fitted to PRRS Host
Genetics Consortium data from 1320 weaned pigs (offspring of 54 sires) that were
experimentally infected with a virulent strain of PRRS virus to obtain genetic
parameter estimates for resistance and tolerance. Resistance was defined as the
inverse of within-host viral load (VL) from 0 to 21 (VL21) or 0 to 42 (VL42) days
post-infection and tolerance as the slope of the reaction-norm of average daily
gain (ADG21, ADG42) on VL21 or VL42. RESULTS: Multi-trait analysis of ADG
associated with either low or high VL was not indicative of genetic variation in
tolerance. Similarly, random regression models for ADG21 and ADG42 with a
tolerance slope fitted for each sire did not result in a better fit to the data
than a model without genetic variation in tolerance. However, the distribution of
data around average VL suggested possible confounding between level and slope
estimates of the regression lines. Augmenting the data with simulated growth
rates of non-infected half-sibs (ADG0) helped resolve this statistical
confounding and indicated that genetic variation in tolerance to PRRS may exist
if genetic correlations between ADG0 and ADG21 or ADG42 are low to moderate.
CONCLUSIONS: Evidence for genetic variation in tolerance of pigs to PRRS was weak
when based on data from infected piglets only. However, simulations indicated
that genetic variance in tolerance may exist and could be detected if comparable
data on uninfected relatives were available. In conclusion, of the two defense
strategies, genetics of tolerance is more difficult to elucidate than genetics of
resistance.
PMID- 28424057
TI - Personalized medicine in Europe: not yet personal enough?
AB - BACKGROUND: Personalized medicine has the potential to allow patients to receive
drugs specific to their individual disease, and to increase the efficiency of the
healthcare system. There is currently no comprehensive overview of personalized
medicine, and this research aims to provide an overview of the concept and
definition of personalized medicine in nine European countries. METHODS: A
targeted literature review of selected health databases and grey literature was
conducted to collate information regarding the definition, process, use, funding,
impact and challenges associated with personalized medicine. In-depth qualitative
interviews were carried out with experts with health technology assessment,
clinical provisioning, payer, academic, economic and industry experience, and
with patient organizations. RESULTS: We identified a wide range of definitions of
personalized medicine, with most studies referring to the use of diagnostics and
individual biological information such as genetics and biomarkers. Few studies
mentioned patients' needs, beliefs, behaviour, values, wishes, utilities,
environment and circumstances, and there was little evidence in the literature
for formal incorporation of patient preferences into the evaluation of new
medicines. Most interviewees described approaches to stratification and
segmentation of patients based on genetic markers or diagnostics, and few
mentioned health-related quality of life. CONCLUSIONS: The published literature
on personalized medicine is predominantly focused on patient stratification
according to individual biological information. Although these approaches are
important, incorporation of environmental factors and patients' preferences in
decision making is also needed. In future, personalized medicine should move from
treating diseases to managing patients, taking into account all individual
factors.
PMID- 28424058
TI - Family members of deceased palliative care patients receiving bereavement
anniversary cards: a survey on the recipient's reactions and opinions.
AB - BACKGROUND: Bereavement support is part of palliative care. Sending out
bereavement anniversary cards is one intervention of follow-up support for the
bereaved. This study evaluated the suitability of bereavement anniversary cards
as an appropriate method in bereavement care. METHODS: A questionnaire was sent
to each card recipient since the starting point of this practice (October 2014
June 2015). Data was analyzed descriptively. RESULTS: 24 of 68 deliverable
questionnaires were returned (response rate 35%). 22 out of 24 recipients felt
pleased receiving the card. No participant felt annoyed on receiving the
bereavement anniversary card; every participant agreed to at least one positive
reaction (i.e. pleased, grateful or consoled). CONCLUSIONS: The participants'
reactions and opinions about receiving the anniversary card were decidedly
positive and indicate the continuation of this practice. Those few less pleased
reactions may be related to timing and the first anniversary of the patients'
death and therefore an expression of grief rather than a dissatisfaction with
bereavement anniversary cards, as such.
PMID- 28424059
TI - Insight into human pubertal growth by applying the QEPS growth model.
AB - BACKGROUND: Computerized mathematical models describing absolute and relative
individual growth during puberty in both cm and standard deviation (SD)-scores
are lacking. The present study aimed to fill this gap, by applying the QEPS-model
that delineates mathematically the specific pubertal functions of the total
growth curve. METHODS: Study population used was the individual growth curves of
the longitudinally followed cohort GrowUp1974 Gothenburg (n = 2280). The QEPS
model describes total height as (T)otal-function: a combination of four shape
invariant growth functions, modified by time-scale and height-scale parameters: a
(Q)uadratic-function for the continuous growth from fetal life to adulthood; a
negative (E)xponential-function adds the rapid, declining fetal/infancy growth; a
(P)ubertal-function the specific pubertal growth spurt; a (S)top-function the
declining growth until adult height. A constructed variable, MathSelect, was
developed for assessing data-quality. CIs and SD-scores for growth estimates were
calculated for each individual. QEPS-model estimates used for pubertal growth;
from the T-function: onset of puberty as minimal height velocity (AgeT ONSET );
mid-puberty as peak height velocity (AgeT PHV ); end of puberty as height
velocity decreased to 1 cm/year (AgeT END ); duration of different intervals and
gain (AgeT ONSET-END and Tpubgain); from the P-function: onset of puberty,
estimated as growth at 1% or 5% (AgeP1 , AgeP5); mid-puberty as 50% (AgeP50) and
PHV (AgeP PHV ); end of pubertal growth at 95 or 99% (AgeP95, AgeP99); duration
of different intervals and pubertal gain (Ppubgain; P max ); from the QES
function: gain (QESpubgain) . RESULTS: Application of these mathematical
estimates for onset, middle and end of puberty of P-function, QES-function, and T
function during puberty showed: the later the onset of puberty, the greater the
adult height; pubertal gain due to the P-function growth was independent of age
at onset of puberty; boys had higher total gain during puberty due to P-function
growth than to QES-function growth; for girls it was reversed. CONCLUSIONS: QEPS
is the first growth model to provide individualized estimates of both the
specific pubertal growth function and the total growth during puberty, with
accompanying SD-scores and Cis for each individual. These QEPS-derived estimates
enable more in-depth analysis of different aspects of pubertal growth than
previously possible.
PMID- 28424060
TI - Effects of a combination treatment of KD5040 and L-dopa in a mouse model of
Parkinson's disease.
AB - BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l
dopa) remains the gold standard pharmacological therapy for patients with
Parkinson's disease (PD), long-term treatment with this drug has been known to
result in several adverse effects, including l -dopa-induced dyskinesia (LID).
Recently, our group reported that KD5040, a modified herbal remedy, had
neuroprotective effects in both in vitro and in vivo models of PD. Thus, the
present study investigated whether KD5040 would have synergistic effects with l
dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects
of KD5040 and l -dopa on motor function, expression levels of substance P (SP)
and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor
cortex were assessed using behavioral assays, immunohistochemistry, Western blot
analyses, and liquid chromatography tandem mass spectrometry in a mouse model of
PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition,
the antidyskinetic effects of KD5040 on pathological movements triggered by l
dopa were investigated by testing abnormal involuntary movements (AIMs) and
measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa
(DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response
element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically
improved the motor function when low-dose l -dopa (LL) was co-administered. In
addition, it significantly reversed MPTP-induced lowering of SP, improved ENK
levels in the basal ganglia, and ameliorated abnormal reduction in glutamate
content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and
controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced
by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa
and alleviated LID. These findings suggest that KD5040 may be used as an adjunct
therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in
patients with PD.
PMID- 28424061
TI - Young people, mental health practitioners and researchers co-produce a Transition
Preparation Programme to improve outcomes and experience for young people leaving
Child and Adolescent Mental Health Services (CAMHS).
AB - BACKGROUND: In the UK young people attending child and adolescent mental health
services (CAMHS) are required to move on, either through discharge or referral to
an adult service, at age 17/18, a period of increased risk for onset of mental
health problems and other complex psychosocial and physical changes. CAMHS
transitions are often poorly managed with negative outcomes for young people.
Better preparation may improve outcomes and experience. This study aimed to co
produce, with young people who had transitioned or were facing transition from
CAMHS, a CAMHS Transition Preparation Programme (TPP), deliverable in routine NHS
settings. METHODS: Eighteen young people, aged 17-22, from three UK National
Health Service (NHS) mental health foundation trusts participated in creative,
participatory research workshops. Seven parents completed short questionnaires.
Thirty clinical staff from two trusts took part in workshops to ensure
deliverability of young people's ideas. Young people were offered co-research
opportunities. RESULTS: Most young people felt anxious, fearful and uncertain on
leaving CAMHS and perceived mental health services as uncaring. Participants
outlined transition procedures and drafted a range of preparation activities,
centred around dedicated Transition Peer Support and a transition booklet, which
should be offered to all CAMHS leavers, irrespective of discharge or transfer to
an adult service. Preparation should aim to build confidence to help young people
take responsibility for themselves and flourish in the adult world: coping or
getting through it was not enough. Some clinicians also felt anxious at
transition and recognised the potential impact on young people of poor
communication and lack of understanding between services. Parents would
appreciate help to support their offspring during the transition period.
Clinicians cited lack of funding and inflexible NHS procedures and policies as
potential barriers to the implementation of young people's ideas. Nine young
people took up co-research opportunities. CONCLUSIONS: Mental health services
underestimate the anxiety of CAMHS leavers. Young people have clear ideas about
the preparation they require to leave CAMHS with the confidence to take
responsibility for their own health care. Close collaboration of NHS staff and
researchers facilitates the implementation of research findings.
PMID- 28424062
TI - Health system factors influencing management of multidrug-resistant tuberculosis
in four European Union countries - learning from country experiences.
AB - BACKGROUND: In the European Union and European Economic Area only 38% of
multidrug-resistant tuberculosis patients notified in 2011 completed treatment
successfully at 24 months' evaluation. Socio-economic factors and patient factors
such as demographic characteristics, behaviour and attitudes are associated with
treatment outcomes. Characteristics of healthcare systems also affect health
outcomes. This study was conducted to identify and better understand the
contribution of health system components to successful treatment of multidrug
resistant tuberculosis. METHODS: We selected four European Union countries to
provide for a broad range of geographical locations and levels of treatment
success rates of the multidrug-resistant tuberculosis cohort in 2009. We
conducted semi-structured interviews following a conceptual framework with
representatives from policy and planning authorities, healthcare providers and
civil society organisations. Responses were organised according to the six
building blocks of the World Health Organization health systems framework.
RESULTS: In the four included countries, Austria, Bulgaria, Spain, and the United
Kingdom, the following healthcare system factors were perceived as key to
achieving good treatment results for patients with multidrug-resistant
tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems
that ensure access to a full course of treatment and support for multidrug
resistant tuberculosis patients; patient-centred approaches with strong
intersectoral collaboration that address patients' emotional and social needs;
motivated and dedicated healthcare workers with sufficient mandate and means to
support patients; and cross-border management of multidrug-resistant tuberculosis
to secure continuum of care between countries. CONCLUSION: We suggest that the
following actions may improve the success of treatment for multidrug-resistant
tuberculosis patients: deployment of rapid molecular diagnostic tests;
development of context-specific treatment guidance and criteria for hospital
admission and discharge in the European context; strengthening patient-centred
approaches; development of collaborative mechanisms to ensure cross-border care,
and development of long-term sustainable financing strategies.
PMID- 28424063
TI - Clinical and cost-effectiveness analysis of early detection of patients at
nutrition risk during their hospital stay through the new screening method CIPA:
a study protocol.
AB - BACKGROUND: Malnutrition is highly prevalent in hospitalized patients and results
in a worsened clinical course as well as an increased length of stay, mortality,
and costs. Therefore, simple nutrition screening systems, such as CIPA (control
of food intake, protein, anthropometry), may be implemented to facilitate the
patient's recovery process. The aim of this study is to evaluate the
effectiveness and cost-effectiveness of implementing such screening tool in a
tertiary hospital, consistent with the lack of similar, published studies on any
hospital nutrition screening system. METHODS: The present study is carried out as
an open, controlled, randomized study on patients that were admitted to the
Internal Medicine and the General and Digestive Surgery ward; the patients were
randomized to either a control or an intervention group (n = 824, thereof 412
patients in each of the two study arms). The control group underwent usual
inpatient clinical care, while the intervention group was evaluated with the CIPA
screening tool for early detection of malnutrition and treated accordingly. CIPA
nutrition screening was performed upon hospital admission and classified positive
when at least one of the following parameters was met: 72 h food intake control <
50%, serum albumin < 3 g/dL, body mass index < 18.5 kg/m2 (or mid-upper arm
circumference <= 22.5 cm). In this case, the doctor decided on whether or not
providing nutrition support. The following variables will be evaluated: hospital
length of stay (primary endpoint), mortality, 3-month readmission, and in
hospital complications. Likewise, the quality of life questionnaires EQ-5D-5 L
are being collected for all patients at hospital admission, discharge, and 3
months post-discharge. Analysis of cost-effectiveness will be performed by
measuring effectiveness in terms of quality-adjusted life years (QALYs). The cost
per patient will be established by identifying health care resource utilization;
cost-effectiveness will be determined through the incremental cost-effectiveness
ratio (ICER). We will calculate the incremental cost per QALY gained with respect
to the intervention. DISCUSSION: This ongoing trial aims to evaluate the cost
effectiveness of implementing the malnutrition screening tool CIPA in a tertiary
hospital. TRIAL REGISTRATION: Clinical Trial.gov ( NCT02721706 ). First
receivevd: March 1, 2016 Last updated: April 8, 2017 Last verified: April 2017.
PMID- 28424064
TI - Effectiveness of triple therapy with direct-acting antivirals for hepatitis C
genotype 1 infection: application of propensity score matching in a national HCV
treatment registry.
AB - BACKGROUND: Observational studies are used to measure the effectiveness of an
intervention in non-experimental, real world scenarios at the population level
and are recognised as an important component of the evidence pyramid. Such data
can be accrued through prospective cohort studies and a patient registry is a
proven method for this type of study. The national hepatitis C (HCV) registry was
established in Ireland in 2012 with the aim of monitoring the clinical and
economic outcomes from new, high cost regimens for the treatment of HCV
infection. A sustained virological response (SVR) 24 weeks following completion
of therapy with interferon-containing regimens is considered a cure. Non
randomisation in these studies can result in confounding or selection bias.
Propensity score (PS) matching is one of a number of statistical tools that can
be used to mitigate the effects of confounding in observational studies. METHODS:
We analysed the data of 309 patients who underwent triple therapy treatment with
telaprevir (TPV) in combination with pegylated-interferon and ribavirin (PR) or
boceprevir (BOC)/PR between June 2012 and December 2014. The decision to initiate
treatment and the selection of the treatment regimen was at the discretion of the
physician. To adjust for confounding, three approaches to propensity score
matching were assessed Adjusted sustained-virological response rates (SVR), odds
ratios, p-values and 95% confidence intervals were calculated from the three PS
matched dataset. RESULTS: Prior to matching, the unadjusted sustained virological
response rates 24 weeks after treatment complete (SVR24) were 74% (n = 158/215)
and 61% (n = 57/94) for telaprevir/PR and boceprevir/PR, respectively. After
matching, adjusted SVR24 rates were between 73-74% and 60-61% for telaprevir/PR
and boceprevir/PR, respectively. CONCLUSION: Efficacy rates were comparable with
those reported in pivotal clinical trials and real world studies. After adjusting
for confounding, we conclude that there was no difference in treatment effect
after PS matching. The small sample size limits the conclusions that can be made
about the effect of PS matching. Propensity score adjustment remains a tool that
can be applied to future analysis, however, we suggest, where possible, using a
larger sample size in order to reduce the uncertainty around the outcomes.
PMID- 28424065
TI - Efficacy of irreversible EGFR-TKIs for the uncommon secondary resistant EGFR
mutations L747S, D761Y, and T854A.
PMID- 28424066
TI - Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA
methylation and lung function decrements among urban children.
AB - BACKGROUND: Both short and long-term exposure to traffic-related air pollutants
have been associated with asthma and reduced lung function. We hypothesized that
short-term indoor exposure to fine particulate matter <2.5 MUm (PM2.5) and
vanadium (V) would be associated with altered buccal cell DNA methylation of
targeted asthma genes and decreased lung function among urban children in a
nested subcohort of African American and Dominican children. METHODS: Six day
integrated levels of air pollutants were measured from children's homes (age 9
14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected
repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4
(IL4), interferon gamma (IFNgamma), inducible nitric oxide synthase (NOS2A),
arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. RESULTS:
Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4
and IFNgamma. In exploratory analyses, V levels were associated with lower
methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or
obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V,
appeared associated with lower lung function (i.e., reduced z-scores for forced
expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and
forced expiratory flow at 25-75% of FVC [FEF25-75]). CONCLUSIONS: Exposure to V
was associated with altered DNA methylation of allergic and proinflammatory
asthma genes implicated in air pollution related asthma. However, short-term
exposure to PM2.5, but not V, appeared associated with decrements in lung
function among urban children.
PMID- 28424067
TI - Preventing parastomal hernias with systematic intraperitoneal specifically
designed mesh.
AB - BACKGROUND: Parastomal hernia is a very common complication after stoma
formation. Current surgical techniques for repairing parastomal hernia have
unsatisfactory results. We aim to assess our preliminary experience with
prophylactic mesh placement at the time of stoma formation. METHODS: Data were
prospectively recorded. A specifically designed mesh made of polyvinyl fluoride
with central conduit (Dynamesh IPST(r)) was fixed using an intra-peritoneal onlay
technique. Safety was evaluated by means of surgical data and frequency of mesh
related complications, efficacy by the rate of parastomal hernias. RESULTS:
Thirty-four patients were included in the study. Three of them died before a year
of follow up (not related to the stoma), so they were excluded. The other 31
patients (11 women and 20 men) were prospectively followed up after different
pathologies resulting in a permanent colostomy. Twelve months after surgery CT
Scan imaging revealed two (6.4%) parastomal hernias, one of them already
clinically suspected. During the follow up, 29% of the patients (n = 9) developed
another type of hernia (incisional, inguinal or both). In five patients (16.1%) a
light stomal retraction of the otherwise slightly prominent ostomy was observed.
Median clinical follow-up was 17.5 months (range 12-34). CONCLUSION: Prophylactic
parastomal mesh placement might be a safe and effective procedure with a
potential to reduce the risk of parastomal hernia. Routine use of this technique
should be further analysed.
PMID- 28424068
TI - Efficacy of a Transdiagnostic internet-based treatment for emotional disorders
with a specific component to address positive affect: Study protocol for a
randomized controlled trial.
AB - BACKGROUND: Emotional disorders (ED) are among the most prevalent mental
disorders. However, less than 50% of people suffering from ED receive the
appropriate treatment. This situation has led to the development of new
intervention proposals based on the transdiagnostic perspective, which tries to
address the underlying processes common to ED. Most of these programs focus
primarily on down-regulating negative affectivity, rather than increasing
strengths and up-regulating positive affectivity. The data suggest the existence
of disturbances in positive affectivity in these disorders, and so new
interventions focusing on these problems are greatly needed. It is also essential
to provide assistance to all the people in need. Information and Communication
Technologies can be very useful. This study aims to evaluate the efficacy of a
transdiagnostic Internet-based treatment for ED in a community sample. The
protocol includes traditional CBT components, as well as a specific component to
address positive affect. We intend to test this protocol, including this specific
component or not, versus a waiting list control group. Moreover, we aim to test
the differential effect of this specific component, and study the effectiveness
(in terms of patients' acceptance) of using a self-applied Internet-based
program. This paper presents the study protocol. METHODS: The study is a
randomized controlled trial. 207 participants will be randomly assigned to:
a)Transdiagnostic Internet-based protocol (TIBP), b)Transdiagnostic Internet
based protocol + positive affect component (TIBP + PA), or c)a Waiting List
control group (WL). Primary outcomes measures will be the BDI-II, the BAI, and
the PANAS. Secondary outcomes will include diagnosis-specific measures of the
principal disorder. Participants' treatment acceptance will also be measured.
Participants will be assessed at pre-, post-treatment, and 3- and 12- month
follow-ups. The data will be analyzed based on the Intention-to-treat principle.
Per protocol analyses will also be performed. DISCUSSION: To the best of our
knowledge, this is the first study of a transdiagnostic Internet-based treatment
for ED with a specific component to up-regulate positive affectivity. This
intervention could contribute to improve the efficiency and effectiveness of
current treatment programs for ED, promote the dissemination of EBTs, and help to
decrease the high prevalence of ED. TRIAL REGISTRATION: ClinicalTrial.gov:
NCT02578758 . Registered 15 October 2015.
PMID- 28424069
TI - AnkPlex: algorithmic structure for refinement of near-native ankyrin-protein
docking.
AB - BACKGROUND: Computational analysis of protein-protein interaction provided the
crucial information to increase the binding affinity without a change in basic
conformation. Several docking programs were used to predict the near-native poses
of the protein-protein complex in 10 top-rankings. The universal criteria for
discriminating the near-native pose are not available since there are several
classes of recognition protein. Currently, the explicit criteria for identifying
the near-native pose of ankyrin-protein complexes (APKs) have not been reported
yet. RESULTS: In this study, we established an ensemble computational model for
discriminating the near-native docking pose of APKs named "AnkPlex". A dataset of
APKs was generated from seven X-ray APKs, which consisted of 3 internal domains,
using the reliable docking tool ZDOCK. The dataset was composed of 669 and 44,334
near-native and non-near-native poses, respectively, and it was used to generate
eleven informative features. Subsequently, a re-scoring rank was generated by
AnkPlex using a combination of a decision tree algorithm and logistic regression.
AnkPlex achieved superior efficiency with >=1 near-native complexes in the 10 top
rankings for nine X-ray complexes compared to ZDOCK, which only obtained six X
ray complexes. In addition, feature analysis demonstrated that the van der Waals
feature was the dominant near-native pose out of the potential ankyrin-protein
docking poses. CONCLUSION: The AnkPlex model achieved a success at predicting
near-native docking poses and led to the discovery of informative characteristics
that could further improve our understanding of the ankyrin-protein complex. Our
computational study could be useful for predicting the near-native poses of
binding proteins and desired targets, especially for ankyrin-protein complexes.
The AnkPlex web server is freely accessible at http://ankplex.ams.cmu.ac.th .
PMID- 28424070
TI - Antidepressant use and cognitive decline in community-dwelling elderly people -
The Three-City Cohort.
AB - BACKGROUND: Cognitive impairment is very common in late-life depression,
principally affecting executive skills and information processing speed. The aim
of the study was to examine the effect of antidepressant treatment on cognitive
performances over a 10-year period. METHODS: The community-based cohort included
7381 participants aged 65 years and above. Five cognitive domains (verbal
fluency, psychomotor speed, executive function, visuospatial skills and global
cognition) were assessed up to five times over 10 years of follow-up. Treatment
groups included participants under a specific antidepressant class at both
baseline and the first follow-up and their follow-up cognitive data were
considered until the last consecutive follow-up with a report of antidepressant
use of the same class. Linear mixed models were used to compare baseline
cognitive performance and cognitive decline over time according to antidepressant
treatment. The models were adjusted for multiple confounders including residual
depressive symptoms assessed by the Center for Epidemiologic Studies-Depression
scale. RESULTS: At baseline, 4.0% of participants were taking antidepressants.
Compared to non-users, tricyclic antidepressant users had lower baseline
performances in verbal fluency, visual memory and psychomotor speed, and
selective serotonin reuptake inhibitor users in verbal fluency and psychomotor
speed. For the two other cognitive abilities, executive function and global
cognition, no significant differences were found at baseline irrespective of the
antidepressant class. Regarding changes over time, no significant differences
were observed in comparison with non-users whatever the cognitive domain, except
for a slight additional improvement over the follow-up in verbal fluency skills
for tricyclic antidepressant users. CONCLUSIONS: In this large elderly general
population cohort, we found no evidence for an association between antidepressant
use and post-treatment cognitive decline over 10 years of follow-up in various
cognitive domains.
PMID- 28424071
TI - Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a
proof-of-concept study in the preoperative window period (ImPACCT).
AB - BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of
colorectal cancer forms a new paradigm for the design and evaluation of subtype
directed therapeutic strategies. The most aggressive subtype - CMS4 - has the
highest chance of disease recurrence. Novel adjuvant therapies for patients with
CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by
expression of mesenchymal and stem-like genes. Previous pre-clinical work has
shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the
related KIT receptor with imatinib is potentially effective against mesenchymal
type colon cancer. In the present study we aim to provide proof for the concept
that imatinib can reduce the aggressive phenotype of primary CMS4 colon cancer.
METHODS: Tumour biopsies from patients with newly diagnosed stage I-III colon
cancer will be analysed with a novel RT-qPCR test to pre-select patients with
CMS4 tumours. Selected patients (n = 27) will receive treatment with imatinib
(400 mg per day) starting two weeks prior to planned tumour resection. To assess
treatment-induced changes in the aggressive CMS4 phenotype, RNA sequencing will
be performed on pre- and post-treatment tissue samples. DISCUSSION: The
development of effective adjuvant therapy for primary colon cancer is hindered by
multiple factors. First, new drugs that may have value in the prevention of
(early) distant recurrence are almost always first tested in patients with
heavily pre-treated metastatic disease. Second, measuring on-target drug effects
and biological consequences in tumour tissue is not commonly a part of the study
design. Third, due to the lack of patient selection tools, clinical trials in the
adjuvant setting require large patient populations. Finally, the evaluation of
recurrence-prevention requires a long-term follow-up. In the ImPACCT trial these
issues are addressed by including newly diagnosed pre-selected patients with CMS4
tumours prior to primary tumour resection, rather than non-selected patients with
late-stage disease. By making use of the pre-operative window period, the
biological effect of imatinib treatment on CMS4 tumours can be rapidly assessed.
Delivering proof-of-concept for drug action in early stage disease should form
the basis for the design of future trials with subtype-targeted therapies in
colon cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02685046 .
Registration date: February 9, 2016.
PMID- 28424072
TI - Prevalence of intimate partner violence and its association with symptoms of
depression; a cross-sectional study based on a female population sample in
Sweden.
AB - BACKGROUND: Intimate Partner Violence (IPV) is the most common type of violence
targeting women. IPV includes acts of physical aggression, sexual coercion,
psychological abuse and controlling behaviors and these forms of violence often
coexist in the same relationship. Living with IPV is associated with serious
mental health outcomes such as depression and depressive symptoms. Few population
based studies from Sweden have investigated the relationship between different
forms of IPV and women's depressive symptoms and even fewer used controlling
behavior as an independent variable in such studies. The aim of this study was
therefore to assess the prevalence of exposure to IPV in terms of controlling
behavior, sexual, and physical violence and their association with self-reported
symptoms of depression in a female population based sample. METHODS: The cross
sectional, population based sample contained 573 women aged 18-65 years randomly
selected in Sweden. Five self-reported symptoms that define depression in the
Diagnostic and Statistical Manual of Mental Disorders were assessed. Physical and
sexual violence were inquired about using the World Health Organization's (WHO)
Violence Against Women Instrument (VAWI), while controlling behavior was assessed
with the Controlling Behavior Scale (CBS). Associations between different forms
of IPV and symptoms of depression were estimated by crude and adjusted odds ratio
(OR) with 95% confidence intervals (CI). RESULTS: Bivariable associations
revealed that women exposed to controlling behavior, had higher OR of depressive
symptoms compared to unexposed women (OR 2.43; 95% CI 1.63-3.63). Women exposed
to physical and sexual violence had also a higher OR of depressive symptoms (OR
3.78; 95% CI 1.99-7.17 and OR 5.10; 95% CI 1.74-14.91 respectively). After
adjusting for socio-demographic and psychosocial covariates, all three forms of
IPV showed statistically significant associations with self-reported symptoms of
depression. CONCLUSIONS: A strength with this study is the analysis of
controlling behavior and its association with self-reported symptoms of
depression in a female population based sample. Exposure to controlling behavior,
physical and sexual violence by an intimate partner were clearly associated with
women's self-reported symptoms of depression.
PMID- 28424073
TI - Systematic review with network meta-analysis: dual therapy for high-risk bleeding
peptic ulcers.
AB - BACKGROUND: Adding a second endoscopic therapy to epinephrine injection might
improve hemostatic efficacy in patients with high-risk bleeding ulcers but the
optimum modality remains unknown. We aimed to estimate the comparative efficacy
of different dual endoscopic therapies for the management of bleeding peptic
ulcers through random-effects Bayesian network meta-analysis. METHODS: Different
databases were searched for controlled trials comparing dual therapy versus
epinephrine monotherapy or epinephrine combined with another second modality
until September, 30 2016. We estimated the ORs for rebleeding, surgery and
mortality among different treatments. Adverse events were also evaluated.
RESULTS: Seventeen eligible articles were included in the network meta-analysis.
The addition of mechanical therapy (OR 0.19, 95% CrI 0.07-0.52 and OR 0.10, 95%
CrI 0.01-0.50, respectively) after epinephrine injection significantly reduced
the probability of rebleeding and surgery. Similarly, patients who received
epinephrine plus thermal therapy showed a significantly decreased rebleeding rate
(OR 0.30, 95% CrI 0.10-0.91), as well as a non-significant reduction in surgery
(OR 0.47, 95% CrI 0.16-1.20). Although differing, epinephrine plus mechanical
therapy did not provide a significant reduction in rebleeding (OR 0.62, 95% CrI
0.19-2.22) and surgery (OR 0.21, 95% CrI 0.03-1.73) compared to epinephrine plus
thermal therapy. Sclerosant failed to confer further benefits and was ranked
highest among the 5 treatments in relation to adverse events. CONCLUSIONS:
Mechanical therapy was the most appropriate modality to add to epinephrine
injection. Epinephrine plus thermal coagulation was effective for controlling
high risk bleeding ulcers. There was no further benefit with sclerosants with
regard to rebleeding or surgery, and sclerosants were also associated with more
adverse events than any other modality.
PMID- 28424074
TI - Implementation and adaptation of the Re-Engineered Discharge (RED) in five
California hospitals: a qualitative research study.
AB - BACKGROUND: Project Re-Engineered Discharge (RED) is an evidence-based strategy
to reduce readmissions disseminated and adapted by various health systems across
the country. To date, little is known about how adapting Project RED from its
original protocol impacts RED implementation and/or sustainability. The goal of
this study was to identify and characterize contextual factors influencing how
five California hospitals adapted and implemented RED and the subsequent impact
on RED program sustainability. METHODS: Participant observation and key informant
and focus group interviews with 64 individuals at five California hospitals
implementing RED in 2012 and 2013 were conducted. These involved hospital
leadership, personnel responsible for Project RED implementation, hospital staff,
and clinicians. Interview transcripts were coded and analyzed using a modified
grounded theory approach and constant comparative analysis. RESULTS: Both
internal and external contextual factors were identified that influenced
hospitals' decisions on RED adaptation and implementation. These also impacted
RED sustainability. External factors included: impending federal penalties for
hospitals with high readmission rates targeting specific diagnoses, and access to
external funding and technical support to help hospitals implement RED. Internal
or organizational level contextual factors included: committed leadership
prioritizing Project RED; RED adaptations; depth, accountability and influence of
the implementation team; sustainability planning; and hospital culture. Only
three of the five hospitals continued Project RED beyond the implementation
period. CONCLUSIONS: The sustainability of RED in participating hospitals was
only possible when hospitals approached RED implementation as a transformational
process rather than a patient safety project, maintained a high level of fidelity
to the RED protocol, and had leadership and an implementation team who embraced
change and failure in the pursuit of better patient care and outcomes. Hospitals
who were unsuccessful in implementing a sustainable RED process lacked all or
most of these components in their approach.
PMID- 28424075
TI - Computational modeling of airway instability and collapse in tracheomalacia.
AB - BACKGROUND: Tracheomalacia (TM) is a condition of excessive tracheal collapse
during exhalation. Both acquired and congenital forms of TM are believed to
result from morphological changes in cartilaginous, fibrous and/or smooth muscle
tissues reducing airway mechanical properties to a degree that precipitates
collapse. However, neither the specific amount of mechanical property reduction
nor the malacic segment lengths leading to life threatening airway collapse in TM
are known. Furthermore, the specific mechanism of collapse is still debated.
METHODS: Computational nonlinear finite element models were developed to
determine the effect of malacic segment length, tracheal diameter, and reduction
in tissue nonlinear elastic properties on the risk for and mechanism of airway
collapse. Cartilage, fibrous tissue, and smooth muscle nonlinear elastic
properties were fit to experimental data from preterm lambs from the literature.
These elastic properties were systematically reduced in the model to simulate TM.
RESULTS: An intriguing finding was that sudden mechanical instability leading to
complete airway collapse occurred in airways when even a 1 cm segment of
cartilage and fibrous tissue properties had a critical reduction in material
properties. In general, increased tracheal diameter, increased malacic segment
length coupled with decreased nonlinear anterior cartilage/fibrous tissue
nonlinear mechanical properties increased the risk of sudden airway collapse from
snap through instability. CONCLUSION: Modeling results support snap through
instability as the mechanism for life threatening tracheomalacia specifically
when cartilage ring nonlinear properties are reduced to a range between fibrous
tissue nonlinear elastic properties (for larger diameter airways > 10 mm) to
mucosa properties (for smaller diameter airways < 6 mm). Although reducing
posterior tracheal smooth muscle properties to mucosa properties decreased
exhalation area, no sudden instability leading to collapse was seen in these
models.
PMID- 28424076
TI - Caregiver's quality of life and its positive impact on symptomatology and quality
of life of patients with schizophrenia.
AB - BACKGROUND: Although the quality of life (QoL) experienced by patients with
schizophrenia has been recognized, few studies have assessed the relationship
between the caregivers' QoL and patients' QoL. METHODS: The study included 253
stabilized outpatients with schizophrenia and their caregivers from 3 Mental
Health Services in Bolivia (N = 83), Chile (N = 85) and Peru (N = 85).
Caregivers' and patients' QoL were respectively assessed using two specific QoL
questionnaires (S-CGQoL and S-QoL 18). We collected socio-demographic information
and clinical data. Multiple linear regressions were performed to determine which
variables were associated with patient's QoL. We tested the following hypothesis
using structural equation modeling (SEM): caregivers' QoL may have an indirect
effect on patients' QoL mediated by their influence of the severity of psychotic
symptoms. RESULTS: In the multivariate analysis, the caregivers' QoL was not
significantly associated with the patients' QoL, except for one QoL dimension
about relationship with family (Beta = 0.23). Among patients' characteristics,
being a woman and Aymara, having lower educational level, unemployment and
severity of symptoms was significantly associated to a lower QoL. The SEM
revealed a moderate significant association between caregivers' QoL and psychotic
symptoms severity (path coefficient = -0.32) and a significant association
between psychotic symptoms severity and patients QoL (path coefficient = -0.40).
The indirect effect of caregivers' QoL on patients' QoL was significant (mediated
effect coefficient = 0.13). CONCLUSION: Improvement of caregiver's QoL may have a
direct impact on the psychotic symptoms of patients and indirectly on patient's
QoL, confirming the need for ongoing family interventions in these regions.
PMID- 28424077
TI - Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia.
AB - BACKGROUND: Metabolomics is a tool that has been used for the diagnosis and
prognosis of specific diseases. The purpose of this study was to examine if
metabolomics could be used as a potential diagnostic and prognostic tool for H1N1
pneumonia. Our hypothesis was that metabolomics can potentially be used early for
the diagnosis and prognosis of H1N1 influenza pneumonia. METHODS: 1H nuclear
magnetic resonance spectroscopy and gas chromatography-mass spectrometry were
used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated
control subjects in the intensive care unit (ICU), and 30 culture-positive plasma
samples from patients with bacterial community-acquired pneumonia drawn within
the first 24 h of hospital admission for diagnosis and prognosis of disease.
RESULTS: We found that plasma-based metabolomics from samples taken within 24 h
of hospital admission can be used to discriminate H1N1 pneumonia from bacterial
pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover,
metabolomics is a highly sensitive and specific tool for the 90-day prognosis of
mortality in H1N1 pneumonia. CONCLUSIONS: This study demonstrates that H1N1
pneumonia can create a quite different plasma metabolic profile from bacterial
culture-positive pneumonia and ventilated control subjects in the ICU on the
basis of plasma samples taken within 24 h of hospital/ICU admission, early in the
course of disease.
PMID- 28424079
TI - Erratum to: Rhodococcus erythropolis as a host for expression, secretion and
glycosylation of Mycobacterium tuberculosis proteins.
PMID- 28424078
TI - Interleukin-6 displays lung anti-inflammatory properties and exerts protective
hemodynamic effects in a double-hit murine acute lung injury.
AB - BACKGROUND: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in
patients with acute respiratory distress syndrome (ARDS). However, its acute
pulmonary hemodynamic effects and role in lung injury have not been investigated
in a clinically relevant murine model of ARDS. METHODS: We used adult C57Bl6 wild
type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous
recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal
lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical
ventilation (MV) for 5 h. Before sacrifice, right ventricular systolic pressure
and cardiac output were measured and total pulmonary resistance was calculated.
After sacrifice, lung inflammation, edema and injury were assessed with
bronchoalveolar lavage (BAL) and histology. In other experiments, right
ventricular systolic pressure was recorded during hypoxic challenges in uninjured
WT mice pretreated with rHuIL-6 or rHuIL-6 + non-selective nitric oxide synthase
inhibitor L-NAME or vehicle. RESULTS: IL-6KO(LPS+MV) mice showed a faster
deterioration of lung elastic properties and more severe bronchoalveolar cellular
inflammation as compared to WT(LPS+MV). Treatment with rHuIL-6 partially
prevented this lung deterioration. Total pulmonary resistance was higher in IL
6KO(LPS+MV) mice and this increase was abolished in rHuIL-6-treated IL-6KO mice.
Finally, rHuIL-6 reduced hypoxic pulmonary vasoconstriction in uninjured WT mice,
an effect that was abolished by co-treatment with L-NAME. CONCLUSIONS: In a
double-hit murine model of ARDS, IL-6 deficient mice experienced more severe
bronchoalveolar cellular inflammation as compared to wild-type littermates.
Furthermore, IL-6 deficiency caused marked acute pulmonary hypertension, which
may be, at least partially, due to vasoactive mechanisms. A dysregulation of
nitric oxide synthase may account for this observation, a hypothesis that will
need to be investigated in future studies.
PMID- 28424080
TI - Erratum to: HDAC6 activity is a non-oncogene addiction hub for inflammatory
breast cancers.
PMID- 28424081
TI - Menu-engineering in restaurants - adapting portion sizes on plates to enhance
vegetable consumption: a real-life experiment.
AB - BACKGROUND: The aim of this research was to investigate whether increased portion
sizes of vegetables and decreased portion sizes of meat on main dishes increased
the amount of vegetables consumed in a real-life restaurant setting without
affecting customer satisfaction. The participants were unaware of the experiment.
METHODS: A cross-over design was used in which three restaurants were randomly
assigned to a sequence of an intervention and control condition. In the
intervention period, the vegetable portion sizes on the plates of main dishes
were doubled (150 g of vegetables instead of 75 g) and the portion sizes of meat
on the plates were reduced by an average of 12.5%. In the control period, the
portion sizes of the main dishes were maintained as usual. In total, 1006
observations and questionnaires were included. RESULTS: Vegetable consumption
from plates was significantly higher during the intervention period (M = 115.5 g)
than during the control period (M = 61.7 g). Similarly, total vegetable
consumption (including side dishes) was significantly higher during the
intervention period (M = 178.0 g) than during the control period (M = 137.0 g).
Conversely, meat consumption was significantly lower during the intervention
period (M = 183.1 g) than during the control period (M = 211.1 g). Satisfaction
with the restaurant visit did not differ between the intervention period (M =
1.27) and control period (M = 1.35). Satisfaction with the main dish was
significantly lower during the intervention period (M = 1.25) than during the
control period (M = 1.38), although in both cases, the scores indicated that
participants remained (very) satisfied with their main dish. CONCLUSIONS: This
study showed that increasing vegetable portions in combination with decreasing
meat portions (unknowingly to the consumer) increased the amount of vegetables
consumed and decreased the amount of meat consumed. Furthermore, despite the
changes in portion sizes, participants remained satisfied with their restaurant
visit and main dish. The findings of this study suggest that modifying portion
size in restaurants is an effective tool for stimulating vegetable consumption
and consequently healthy and sustainable diets.
PMID- 28424083
TI - Erratum to: The impact of co-infections on fish: a review.
PMID- 28424082
TI - Subventricular zones: new key targets for glioblastoma treatment.
AB - BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic
factors of survival and patterns of recurrence among patients with glioblastoma.
METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our
Cancer Center between 2006 and 2010 were identified. All patients received
surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral
(iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively
segmented and radiation dose-volume histograms were generated. Multivariate
analysis using the Cox proportional hazards model was assessed to examine the
relationship between prognostic factors and time to progression (TTP) or overall
survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up,
OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5
26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate
analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs
41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose
bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a
significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation
dose coverage was compatible with an hippocampal sparing. On multivariate
analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor
prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047,
respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as
insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor
prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest
for optimizing glioblastoma treatment.
PMID- 28424084
TI - Durable complete remission with aromatase inhibitor therapy in a patient with
metastatic uterine carcinosarcoma with poor performance status and coagulation
disorders: a case report.
AB - BACKGROUND: Chemotherapy is considered the most appropriate treatment for
metastatic uterine sarcoma, despite its limited efficacy. No other treatment has
been conclusively proved to be a real alternative, but some reports suggest that
anti-hormonal therapy could be active in a small subset of patients. We report
the case of a patient with metastatic uterine carcinosarcoma with positive
hormonal receptors and a complete pathological response. CASE PRESENTATION: A 54
year-old white woman presented to our emergency room with hypovolemic shock and
serious vaginal bleeding. After stabilization, she was diagnosed as having a
locally advanced uterine carcinosarcoma with lymph nodes and bone metastatic
disease. In order to control the bleeding, palliative radiotherapy was
administered. Based on the fact that positive hormone receptors were found in the
biopsy, non-steroidal aromatase inhibitor therapy with letrozole was started. In
the following weeks, her general status improved and restaging imaging tests
demonstrated a partial response of the primary tumor. Ten months after initiating
aromatase inhibitor therapy, she underwent a radical hysterectomy and the
pathological report showed a complete response. After completing 5 years of
treatment, aromatase inhibitor therapy was stopped. She currently continues free
of disease, without further therapy, and maintains a normal and active life.
CONCLUSIONS: This case shows that patients with uterine carcinosarcoma and
positive hormone receptors may benefit from aromatase inhibitor therapy. A
multidisciplinary strategy that includes local therapies such as radiation and/or
surgery should be considered the mainstay of treatment. Systemic therapies such
as hormone inhibitors should be taken into consideration and deserve further
clinical research in the era of precision medicine.
PMID- 28424086
TI - Questioning the application of risk of bias tools in appraising evidence from
natural experimental studies: critical reflections on Benton et al., IJBNPA 2016.
AB - We recently read the article by Benton et al. which reviewed risk of bias in
natural experimental studies investigating the impact of the built environment on
physical activity (Benton et al., 2016; Int J Behav Nutr Phys Act 13:107). As a
technical exercise in assessing risk of bias to understand study quality, we
found the results of this study both interesting and potentially useful. However,
it prompted a number of concerns with the use of risk of bias tools for assessing
the quality of evidence from studies exploiting natural experiments. As we
discuss in this commentary, the rigid application of such tools could have
adverse effects on the uptake and use of natural experiments in population health
research and practice.
PMID- 28424085
TI - The within-host population dynamics of Mycobacterium tuberculosis vary with
treatment efficacy.
AB - BACKGROUND: Combination therapy is one of the most effective tools for limiting
the emergence of drug resistance in pathogens. Despite the widespread adoption of
combination therapy across diseases, drug resistance rates continue to rise,
leading to failing treatment regimens. The mechanisms underlying treatment
failure are well studied, but the processes governing successful combination
therapy are poorly understood. We address this question by studying the
population dynamics of Mycobacterium tuberculosis within tuberculosis patients
undergoing treatment with different combinations of antibiotics. RESULTS: By
combining very deep whole genome sequencing (~1000-fold genome-wide coverage)
with sequential sputum sampling, we were able to detect transient genetic
diversity driven by the apparently continuous turnover of minor alleles, which
could serve as the source of drug-resistant bacteria. However, we report that
treatment efficacy has a clear impact on the population dynamics: sufficient drug
pressure bears a clear signature of purifying selection leading to apparent
genetic stability. In contrast, M. tuberculosis populations subject to less drug
pressure show markedly different dynamics, including cases of acquisition of
additional drug resistance. CONCLUSIONS: Our findings show that for a pathogen
like M. tuberculosis, which is well adapted to the human host, purifying
selection constrains the evolutionary trajectory to resistance in effectively
treated individuals. Nonetheless, we also report a continuous turnover of minor
variants, which could give rise to the emergence of drug resistance in cases of
drug pressure weakening. Monitoring bacterial population dynamics could therefore
provide an informative metric for assessing the efficacy of novel drug
combinations.
PMID- 28424087
TI - Heroes of peer review: Robert Lowe.
AB - In the second of our series of articles celebrating peer reviewers, we talk to
Robert Lowe, who is a Lecturer in computational biology at Queen Mary University
of London, UK, and a valued reviewer for Genome Biology.
PMID- 28424088
TI - Research Exploring Physical Activity in Care Homes (REACH): study protocol for a
randomised controlled trial.
AB - BACKGROUND: As life expectancy increases and the number of older people,
particularly those aged 85 years and over, expands there is an increase in demand
for long-term care. A large proportion of people in a care home setting spend
most of their time sedentary, and this is one of the leading preventable causes
of death. Encouraging residents to engage in more physical activity could deliver
benefits in terms of physical and psychological health, and quality of life. This
study is the final stage of a programme of research to develop and preliminarily
test an evidence-based intervention designed to enhance opportunities for
movement amongst care home residents, thereby increasing levels of physical
activity. METHODS/DESIGN: This is a cluster randomised feasibility trial, aiming
to recruit at least 8-12 residents at each of 12 residential care homes across
Yorkshire, UK. Care homes will be randomly allocated on a 1:1 basis to receive
either the intervention alongside usual care, or to continue to provide usual
care alone. Assessment will be undertaken with participating residents at
baseline (prior to care home randomisation) and at 3, 6, and 9 months post
randomisation. Data relating to changes in physical activity, physical function,
level of cognitive impairment, mood, perceived health and wellbeing, and quality
of life will be collected. Data at the level of the home will also be collected
and will include staff experience of care, and changes in the numbers and types
of adverse events residents experience (for example, hospital admissions, falls).
Details of National Health Service (NHS) usage will be collected to inform the
economic analysis. An embedded process evaluation will obtain information to test
out the theory of change underpinning the intervention and its acceptability to
staff and residents. DISCUSSION: This feasibility trial with embedded process
evaluation and collection of health economic data will allow us to undertake
detailed feasibility work to inform a future large-scale trial. It will provide
valuable information to inform research procedures in this important but
challenging area. TRIAL REGISTRATION: ISRCTN registry, ISRCTN16076575 .
Registered on 25 June 2015.
PMID- 28424089
TI - Feasibility of uterine preservation in the management of early-stage uterine
adenosarcomas: a single institute experience.
AB - BACKGROUND: We aimed to evaluate the efficacy and the safety of uterine
preservation in patients with early-stage uterine adenosarcoma who want to
preserve future fertility. METHODS: We performed a retrospective review of
patients with stage I uterine adenosarcoma diagnosed and treated at a single
institute from 1998 through 2014. RESULTS: Among the total of 31 patients,
uterine preservation surgery was performed in 7 of the nulliparas. Of the 7
patients receiving uterine preservation surgery, 3 showed no evidence of disease
(NED), 2 had persistent disease confined to the uterus, and 2 were alive with
disease (AWD) after recurrence. One patient with an NED status had a vaginal
delivery at term. In the uterine preservation group, 1 patient had sarcomatous
overgrowth at the time of diagnosis and experienced disease recurrence. In the
hysterectomy group, 3 of 24 patients had tumor recurrence. Of the five patients
with tumor recurrence, four (80%) had sarcomatous overgrowth at diagnosis and it
was significantly associated with recurrence by univariate analysis (OR 13.3, p =
0.027). CONCLUSIONS: Uterine preservation represents a possible treatment option
for young female patients who want to maintain fertility. However, a detailed
explanation of the risk of recurrence is necessary, especially in patients with
sarcomatous overgrowth, which seems to be associated with a higher risk of
recurrence. TRIAL REGISTRATION: Retrospectively registered.
PMID- 28424090
TI - Targeted endomyocardial biopsy guided by real-time cardiovascular magnetic
resonance.
AB - BACKGROUND: Endomyocardial biopsies (EMB) are an important diagnostic tool for
myocarditis and other infiltrative cardiac diseases. Routinely, biopsies are
obtained under fluoroscopic guidance with a substantial radiation burden. Despite
procedural success, there is a large sampling error caused by missing the
affected myocardium. Therefore, multiple (>6) biopsies are taken in the clinical
setting. In cardiovascular magnetic resonance (CMR), late gadolinium enhancement
(LGE) depicts areas of affected myocardium in myocarditis or in other
infiltrative cardiomyopathies. Thus, targeted biopsy under real-time CMR image
guidance might reduce the problem of sampling error. METHODS: Seven minipigs of
the Goettingen strain underwent radiofrequency ablation in the left ventricle. At
least two focal lesions were induced on the lateral wall in five and the apex in
two animals. Each ablation lesion was created by two consecutive 30 sec ablations
(max. 30 W, temperature 60-64 degrees C). Biopsies were taken immediately after
lesion induction using a commercially available 7 F conventional bioptome under
fluoroscopic guidance at the ablation site. Afterwards the animals underwent CMR
and lesion visualization by LGE at 3T. The lesions were then targeted and
biopsied under CMR-guidance using a MR-conditional bioptome guided by a steerable
catheter. Interactive real-time (RT) visualization of the intervention on an in
room monitor was based on radial FLASH with nonlinear inverse reconstruction
(NLINV) at a temporal resolution of 42 ms. All samples underwent a standard
histological evaluation. RESULTS: Radiofrequency ablation was successful in all
animals. Fluoroscopy-guided biopsies were performed with a success rate of 6/6
minipigs - resulting in a nonlethal pericardial effusion in one animal.
Visualization of radiofrequency lesions by CMR was successful in 7/7 minipig,
i.e. at least one lesion was clearly visible. Localization and tracking of the
catheters and the bioptome using interactive control of the imaging plane was
achieved in 6/6 MP; however in the animal with a large pericardial effusion after
EMB under fluoroscopy no further EMB was attempted for safety reasons. Biopsies
under interactive RT-CMR guidance were successfully performed in 5/6 animals, in
one animal the bioptome reached the lesion, however the forceps did not cut out a
sample. Specimens obtained under CMR guidance contained part of the lesion in
6/15 (40%) myocardial specimens and in 4/5 (80%) animals in which samples were
achieved. Conventional biopsies revealed ablation lesions in 4/17 (23.5%)
specimens in 3/6 minipigs (50%). CONCLUSION: Focal lesions induced by
radiofrequency ablation in a minipig model are a useful tool for CMR-guided
biopsy studies. In contrast to fluoroscopy, CMR provides excellent visualization
of lesions. Interactive real-time CMR allows excellent passive tracking of the
instruments and EMB provides significantly superior sampling accuracy compared to
fluoroscopy-guided biopsies. Nonetheless, further improvements of MR-compatible
bioptomes and guiding catheters are essential before applying this method in a
clinical setting.
PMID- 28424091
TI - Investigations into the association between soil-transmitted helminth infections,
haemoglobin and child development indices in Manufahi District, Timor-Leste.
AB - BACKGROUND: Timor-Leste has a high prevalence of soil-transmitted helminth (STH)
infections. High proportions of the population have been reported as being
anaemic, and extremely high proportions of children as stunted or wasted. There
have been no published analyses of the contributions of STH to these morbidity
outcomes in Timor-Leste. METHODS: Using baseline cross-sectional data from 24
communities (18 communities enrolled in a cluster randomised controlled trial,
and identically-collected data from six additional communities), analyses of the
association between STH infections and community haemoglobin and child
development indices were undertaken. Stool samples were assessed for STH using
qPCR and participant haemoglobin, heights and weights were measured.
Questionnaires were administered to collect demographic and socioeconomic data.
Intensity of infection was categorised using correlational analysis between qPCR
quantification cycle values and eggs per gram of faeces equivalents, with
algorithms generated from seeding experiments. Mixed-effects logistic and
multinomial regression were used to assess the association between STH infection
intensity classes and anaemia, and child stunting, wasting and underweight.
RESULTS: Very high stunting (60%), underweight (60%), and wasting (20%) in
children, but low anaemia prevalence (15%), were found in the study communities.
STH were not significantly associated with morbidity outcomes. Male children and
those in the poorest socioeconomic quintile were significantly more likely to be
moderately and severely stunted. Male children were significantly more likely
than female children to be severely underweight. Increasing age was also a risk
factor for being underweight. Few risk factors emerged for wasting in these
analyses. CONCLUSIONS: According to World Health Organization international
reference standards, levels of child morbidity in this population constitute a
public health emergency, although the international reference standards need to
be critically evaluated for their applicability in Timor-Leste. Strategies to
improve child development and morbidity outcomes, for example via nutrition and
iron supplementation programmes, are recommended for these communities. Despite
the apparent lack of an association from STH in driving anaemia, stunting,
wasting and underweight, high endemicity suggests a need for STH control
strategies. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
Registry ACTRN12614000680662 ; retrospectively registered.
PMID- 28424092
TI - Analyzing the association between fish consumption and osteoporosis in a sample
of Chinese men.
AB - BACKGROUND: The main purpose of this study was to estimate the associations
between frequency of fish food consumption and osteoporosis (OP) in general
Chinese men. METHODS: We conducted a large-scale, community-based, cross
sectional study to investigate the associations by using self-report
questionnaire to access frequency of fish food intake. A total of 1092 men were
available for data analysis in this study. Multiple regression models controlling
for confounding factors to include frequency of fish food consumption variable
were performed to investigate the relationships for OP. RESULTS: Positive
correlations between frequency of fish food consumption and T score were reported
(beta = 0.084, P value = 0.025). Multiple regression analysis indicated that the
frequency of fish food consumption was significantly associated with OP (P < 0.05
for model 1 and model 2). The men with high frequency of fish food consumption
had a lower prevalence of OP. CONCLUSIONS: The findings indicated that frequency
of fish food consumption was independently and significantly associated with OP.
The prevalence of OP was less frequent in Chinese men preferring fish food
habits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02451397
retrospectively registered 28 May 2015.
PMID- 28424093
TI - A survey of national and multi-national registries and cohort studies in juvenile
idiopathic arthritis: challenges and opportunities.
AB - BACKGROUND: To characterize the existing national and multi-national registries
and cohort studies in juvenile idiopathic arthritis (JIA) and identify
differences as well as areas of potential future collaboration. METHODS: We
surveyed investigators from North America, Europe, and Australia about existing
JIA cohort studies and registries. We excluded cross-sectional studies. We
captured information about study design, duration, location, inclusion criteria,
data elements and collection methods. RESULTS: We received survey results from 18
studies, including 11 national and 7 multi-national studies representing 37
countries in total. Study designs included inception cohorts, prevalent disease
cohorts, and new treatment cohorts (several of which contribute to
pharmacosurveillance activities). Despite numerous differences, the data elements
collected across the studies was quite similar, with most studies collecting at
least 5 of the 6 American College of Rheumatology core set variables and the data
needed to calculate the 3-variable clinical juvenile disease activity score. Most
studies were collecting medication initiation and discontinuation dates and were
attempting to capture serious adverse events. CONCLUSION: There is a wide-range
of large, ongoing JIA registries and cohort studies around the world. Our survey
results indicate significant potential for future collaborative work using data
from different studies and both combined and comparative analyses.
PMID- 28424094
TI - Electrical control of calcium oscillations in mesenchymal stem cells using
microsecond pulsed electric fields.
AB - BACKGROUND: Human mesenchymal stem cells are promising tools for regenerative
medicine due to their ability to differentiate into many cellular types such as
osteocytes, chondrocytes and adipocytes amongst many other cell types. These
cells present spontaneous calcium oscillations implicating calcium channels and
pumps of the plasma membrane and the endoplasmic reticulum. These oscillations
regulate many basic functions in the cell such as proliferation and
differentiation. Therefore, the possibility to mimic or regulate these
oscillations might be useful to regulate mesenchymal stem cells biological
functions. METHODS: One or several electric pulses of 100 MUs were used to induce
Ca2+ spikes caused by the penetration of Ca2+ from the extracellular medium,
through the transiently electropermeabilized plasma membrane, in human adipose
mesenchymal stem cells from several donors. Attached cells were preloaded with
Fluo-4 AM and exposed to the electric pulse(s) under the fluorescence microscope.
Viability was also checked. RESULTS: According to the pulse(s) electric field
amplitude, it is possible to generate a supplementary calcium spike with
properties close to those of calcium spontaneous oscillations, or, on the
contrary, to inhibit the spontaneous calcium oscillations for a very long time
compared to the pulse duration. Through that inhibition of the oscillations, Ca2+
oscillations of desired amplitude and frequency could then be imposed on the
cells using subsequent electric pulses. None of the pulses used here, even those
with the highest amplitude, caused a loss of cell viability. CONCLUSIONS: An easy
way to control Ca2+ oscillations in mesenchymal stem cells, through their
cancellation or the addition of supplementary Ca2+ spikes, is reported here.
Indeed, the direct link between the microsecond electric pulse(s) delivery and
the occurrence/cancellation of cytosolic Ca2+ spikes allowed us to mimic and
regulate the Ca2+ oscillations in these cells. Since microsecond electric pulse
delivery constitutes a simple technology available in many laboratories, this new
tool might be useful to further investigate the role of Ca2+ in human mesenchymal
stem cells biological processes such as proliferation and differentiation.
PMID- 28424095
TI - Safety and effectiveness of oral propranolol for infantile hemangiomas started
before 5 weeks and after 5 months of age: an Italian multicenter experience.
AB - BACKGROUND: Despite not being licensed for the treatment of infantile hemangiomas
(IH) in infants younger than 5 weeks or older than 5 months, propranolol is often
used in these age groups to prevent or to treat potentially severe complications.
The objective of the present study was to review the experience of 8 Italian
pediatric and dermatologic centers regarding propranolol treatment for IH started
before 5 weeks or after 5 months of age. METHODS: We retrospectively reviewed the
records of patients followed up for IH, on propranolol treatment started before 5
weeks or after 5 months of age, and collected information on sociodemographic
data, treatment indications, IH involution, IH relapse, and treatment side
effects. RESULTS: A total of 343 patients were enrolled; 15 were started on
propranolol before 5 weeks (group 1), 328 were started after 5 months of age
(group 2). The most frequent indications were permanent aesthetical disfigurement
(91.8%) and function threatening complications (42.6%). In most cases, the
treatment was effective. The involution was partial in 67.7% of patients. In
11.8% of cases a relapse was observed. No relapse was observed in group 1.
Treatment complications were reported in 15.8% of children, most frequently sleep
disorders (6.6%), followed by irritability (5.1%) and diarrhea (2.2%). Only a
case of mild constipation was observed in group 1. CONCLUSION: The safety and
effectiveness profile of propranolol in infants younger than 5 weeks or older
than 5 months may be acceptable. Taking in account propranolol's potential in
preventing severe complications, further studies should assess the acceptability
of propranolol treatment, especially in the <5-week age group .
PMID- 28424096
TI - Metabolic and proteomic analyses of product selectivity and redox regulation in
Clostridium pasteurianum grown on glycerol under varied iron availability.
AB - BACKGROUND: Clostridium pasteurianum as an emerging new microbial cell factory
can produce both n-butanol (BuOH) and 1,3-propanediol (1,3-PDO), and the pattern
of product formation changes significantly with the composition of the culture
medium. Among others iron content in the medium was shown to strongly affect the
products selectivity. However, the mechanism behind this metabolic regulation is
still unclear. For a better understanding of such metabolic regulation and for
process optimization, we carried out fermentation experiments under either iron
excess or iron limitation conditions, and performed metabolic, stoichiometric and
proteomic analyses. RESULTS: 1,3-PDO is most effectively produced under iron
limited condition (Fe-), whereas 1,3-PDO and BuOH were both produced under iron
rich condition (Fe+). With increased iron availability the BuOH/1,3-PDO ratio
increased significantly from 0.27 mol/mol (at Fe-) to 1.4 mol/mol (at Fe+).
Additionally, hydrogen production was enhanced significantly under Fe+ condition.
Proteomic analysis revealed differentiated expression of many proteins including
several ones of the central carbon metabolic pathway. Among others, pyruvate:
ferredoxin oxidoreductase, hydrogenases, and several electron transfer
flavoproteins was found to be strongly up-regulated under Fe+ condition, pointing
to their strong involvement in the regeneration of the oxidized form of
ferredoxin, and consequently their influences on the product selectivity in C.
pasteurianum. Of particular significance is the finding that H2 formation in C.
pasteurianum is coupled to the ferredoxin-dependent butyryl-CoA dehydrogenase
catalyzed reaction, which significantly affects the redox balance and thus the
product selectivity. CONCLUSIONS: The metabolic, stoichiometric and proteomic
results clearly show the key roles of hydrogenases and ferredoxins dependent
reactions in determining the internal redox balance and hence product
selectivity. Not only the NADH pool but also the regulation of the ferredoxin
pool could explain such product variation under different iron conditions.
PMID- 28424097
TI - Unusual course of generalized lymph node primary plasmacytoma in a patient with
Sjogren's syndrome: a case report.
AB - BACKGROUND: Primary lymph node plasmacytoma is a rare disease that typically
involves lymph nodes of the neck. In only 15% of cases is the disease
generalized. Here, we present a case of generalized lymph node plasmacytoma in a
patient with Sjogren's syndrome with an unusual course. CASE PRESENTATION: A 48
year-old white woman presented to our hospital with enlargement of groups of
lymph nodes, liver, and spleen. Her medical history was consistent with a 12-year
course of Sjogren's syndrome. Blood and urine immunochemistry showed a massive
(72 g/l) M-gradient formed from immunoglobulin Akappa in the serum and monoclonal
free kappa-type light chains in her urine. A skeletal X-ray revealed no bone
destruction. Cytological and histological bone marrow assays showed no signs of
plasma cell infiltration. The microarchitecture of her neck and inguinal lymph
nodes was destroyed. Only small remnants of B cell follicles were found, while
the interfollicular areas were expanded and infiltrated by CD138, MuM1, CD43, and
IgAkappa-positive plasma cells. After nine cycles of doxorubicin,
cyclophosphamide, vincristine, and prednisolone chemotherapy, complete remission
was achieved. However, the lymphoma relapsed 3 months later, with histological
verification in her femoral lymph node. Despite the absence of subsequent
adequate therapy, she gradually achieved complete remission of plasmacytoma with
the disappearance of paraproteins. CONCLUSIONS: Currently, primary lymph node
plasmacytoma is generally considered a nodal marginal zone lymphoma with an
extensive plasmacytic differentiation. In our case, despite the critical
histological and immunohistochemical evaluation of three lymph node biopsies from
different anatomical areas at different times, no signs of nodal marginal zone
lymphoma were found. An 18-year follow-up of our patient with primary lymph node
plasmacytoma demonstrated an extremely unusual clinical course. Initially,
primary lymph node plasmacytoma was refractory to chemotherapy. However,
subsequently, she underwent a complete spontaneous remission of plasmacytoma.
PMID- 28424098
TI - Identification of odorant-binding protein genes in Galeruca daurica (Coleoptera:
Chrysomelidae) and analysis of their expression profiles.
AB - Odorant-binding proteins (OBPs) play a fundamental role in insect olfaction. In
recent years, Galeruca daurica (Joannis) (Coleoptera: Chrysomelidae) has become
one of the most important insect pests in the Inner Mongolian grasslands of
China. This pest only feeds on the species of Allium plants, implying the central
role of olfaction in its search for specific host plants. However, the olfaction
related proteins have not been investigated in this beetle. In this study, we
identified 29 putative OBP genes, namely GdauOBP1-29, from the transcriptome
database of G. daurica assembled in our laboratory by using RNA-Seq. All 29 genes
had the full-length open reading frames except GdauOBP29, encoding proteins in
length from 119 to 202 amino acids with their predicted molecular weights from 12
to 22 kDa with isoelectric points from 3.88 to 8.84. Predicted signal peptides
consisting of 15-22 amino acid residues were found in all except GdauOBP6,
GdauOBP13 and GdauOBP29. The amino acid sequence identity between the 29 OBPs
ranged 8.33-71.83%. GdauOBP1-12 belongs to the Classic OBPs, while the others
belong with the Minus-C OBPs. Phylogenetic analysis indicated that GdauOBPs are
the closest to CbowOBPs from Colaphellus bowringi. RT-PCR and qRT-PCR analyses
showed that all GdauOBPs were expressed in adult antennae, 11 of which with
significant differences in their expression levels between males and females.
Most GdauOBPs were also expressed in adult heads (without antennae), thoraxes,
abdomens, legs and wings. Moreover, the expression levels of the GdauOBPs varied
during the different development stages of G. daurica with most GdauOBPs
expressed highly in the adult antennae but scarcely in eggs and pupae. These
results provide insights for further research on the molecular mechanisms of
chemical communications in G. daurica.
PMID- 28424099
TI - Influence of opacification in the frontal recess on frontal sinusitis.
AB - OBJECTIVES: This study aimed to radiologically evaluate the influence of
inflammatory changes in frontal recess cells on frontal sinusitis. METHODS: A
total of 93 patients (186 sides) who underwent primary sinonasal surgery at Hyogo
College of Medicine were enrolled in 2015 and 2016. Opacification of agger nasi,
fronto-ethmoidal, ethmoid bulla, suprabullar and frontal bulla cells was
determined by pre-operative computed tomography and its influence on frontal
sinusitis was investigated. RESULTS: In all, 42 per cent of 186 sides were
affected by frontal sinusitis. Agger nasi, ethmoid bulla, fronto-ethmoidal,
suprabullar and frontal bulla cells were identified in 99 per cent, 100 per cent,
38 per cent, 69 per cent, and 16 per cent of sides, respectively. The presence of
frontal recess cells and frontal ostium size did not significantly influence
frontal sinusitis development. However, opacification of agger nasi, type 1
fronto-ethmoidal and suprabullar cells significantly influenced frontal sinusitis
development. CONCLUSION: Frontal sinusitis is caused by inflammatory changes in
frontal recess cells.
PMID- 28424100
TI - Out-patient flexible carbon dioxide laser surgery for benign laryngopharyngeal
pathologies via transnasal flexible laryngo-oesophagoscopy.
AB - OBJECTIVE: To assess the feasibility and outcomes of flexible carbon dioxide
laser surgery in a clinic-based setting. METHODS: A prospective study was
conducted in a tertiary centre. Clinical indications, clinical outcomes and
patient satisfaction were assessed in patients treated with flexible carbon
dioxide laser surgery via transnasal endoscopy and followed up over a period of
up to nine months. Patients who were not fit for general anaesthesia or those
with lesions that cannot be accessed by micro-laryngoscopy were included.
RESULTS: A total of 13 patients (14 procedures) were included. Clinical
indications for surgery were small-to-medium sized benign pathologies in the
upper aero-digestive tract. Patient satisfaction was assessed using a validated
questionnaire. CONCLUSION: Early data suggest that flexible carbon dioxide laser
is a versatile and feasible instrument with potential applications for a range of
benign pathologies in the upper aero-digestive tract.
PMID- 28424101
TI - Limited impacts of truck-based ultra-low-volume applications of mosquito
adulticides on mortality in honey bees (Apis mellifera).
AB - Adulticides applied against mosquitoes can reduce vector populations during times
of high arbovirus transmission. However, impacts of these insecticides on
pollinators and other non-target organisms are of concern to mosquito control
professionals, beekeepers and others. We evaluated mortality of Culex
quinquefasciatus and Apis mellifera when caged insects were exposed to low and
high label rates of four common adulticides (Aqua-PursuitTM [permethrin], Duet(r)
[prallethrin + sumithrin], Fyfanon(r) [malathion] and Scourge(r) [resmethrin]) at
six distances up to 91.4 m from a truck-mounted ultra-low-volume sprayer. Honey
bee mortality was both absolutely low (61 m had limited impacts on honey bee
mortality while providing effective mosquito control.
PMID- 28424102
TI - Gaining insights into the ecological role of the New Zealand sole (Peltorhamphus
novaezeelandiae) through parasites.
AB - Despite the fact that tapeworms comprise the bulk of parasite communities of
sharks in marine ecosystems, little is known about their life cycles and, more
specifically, about the potential intermediate hosts they utilize as transmission
routes. In the absence of morphological features required for specific
identification of larval tapeworms from potential intermediate hosts, recent
molecular advances have contributed to linking larval and adult parasites and, in
some instances, uncovering unknown trophic links. Host-parasite checklists are
often the first source of information consulted to assess the diversity and host
specificity of parasites, and provide insights into parasite identification.
However, these host-parasite checklists are only useful if they encompass the
full spectrum of associations between hosts and parasites. A checklist of New
Zealand fishes and their parasites has been published, but recent parasitological
examinations of commercial fish species reveal that the checklist appears to be
far from complete. We focused our current study on a comprehensive survey of
macroparasites of a commercial species, the New Zealand sole (Peltorhamphus
novaezeelandiae) off the coast of Otago, New Zealand. Specifically, we were
expecting to recover marine tapeworms using sharks as their definitive hosts that
are generally underreported in parasite surveys. The parasites recovered included
tapeworms, flukes, round worms and thorny-headed worms. Surprisingly, a large
proportion of the non-tapeworm parasites we recovered were not previously
reported from this fish species. A discussion on the potential ecological roles
played by this fish species in the transmission of parasites is included.
PMID- 28424103
TI - Olfactory disturbances in ageing with and without dementia: towards new
diagnostic tools.
AB - BACKGROUND: Olfactory disorders increase with age and often affect elderly people
who have pre-dementia or dementia. Despite the frequent occurrence of olfactory
changes at the early stages of neurodegenerative disorders such as Alzheimer's
disease, olfactory disorders are rarely assessed in daily clinical practice,
mainly due to a lack of standardised assessment tools. The aims of this review
were to (1) summarise the existing literature on olfactory disorders in ageing
populations and patients with neurodegenerative disorders; (2) present the
strengths and weaknesses of current olfactory disorder assessment tools; and (3)
discuss the benefits of developing specific olfactory tests for neurodegenerative
diseases. METHODS: A systematic review was performed of literature published
between 2000 and 2015 addressing olfactory disorders in elderly people with or
without Alzheimer's disease or other related disorders to identify the main tools
currently used for olfactory disorder assessment. RESULTS: Olfactory disorder
assessment is a promising method for improving both the early and differential
diagnosis of Alzheimer's disease. However, the current lack of consensus on which
tests should be used does not permit the consistent integration of olfactory
disorder assessment into clinical settings. CONCLUSION: Otolaryngologists are
encouraged to use olfactory tests in older adults to help predict the development
of neurodegenerative diseases. Olfactory tests should be specifically adapted to
assess olfactory disorders in Alzheimer's disease patients.
PMID- 28424104
TI - Assessing the impact of conversational overlap in content on child language
growth.
AB - When engaged in conversation, both parents and children tend to re-use words that
their partner has just said. This study explored whether proportions of maternal
and/or child utterances that overlapped in content with what their partner had
just said contributed to growth in mean length of utterance (MLU), developmental
sentence score, and vocabulary diversity over time. We analyzed the New England
longitudinal corpus from the CHILDES database, comprising transcripts of mother
child conversations at 14, 20, and 32 months, using the CHIP command to compute
proportions of utterances with overlapping content. Rates of maternal overlap,
but not child overlap, at earlier time-points predicted child language outcomes
at later time-points, after controlling for earlier child MLU. We suggest that
maternal overlap plays a formative role in child language development by
providing content that is immediately relevant to what the child has in mind.
PMID- 28424105
TI - Specific impact of stimulant, alcohol and cannabis use disorders on first-episode
psychosis: 2-year functional and symptomatic outcomes.
AB - BACKGROUND: Many studies have concluded that cannabis use disorder (CUD)
negatively influences outcomes in first-episode psychosis (FEP). However, few
have taken into account the impact of concurrent misuse of other substances.
METHODS: This 2-year, prospective, longitudinal study of FEP patients, aged
between 18 and 30 years, admitted to early intervention programs in Montreal,
Quebec, Canada, examined the specific influence of different substance use
disorders (SUD) (alcohol, cannabis, cocaine, amphetamines) on service
utilization, symptomatic and functional outcomes in FEP. RESULTS: Drugs and
alcohol were associated with lower functioning, but drugs had a greater negative
impact on most measures at 2-year follow-up. Half of CUD patients and more than
65% of cocaine or amphetamine abusers presented polysubstance use disorder (poly
SUD). The only group that deteriorated from years 1 to 2 (symptoms and
functioning) were patients with persistent CUD alone. Outcome was worse in CUD
than in the no-SUD group at 2 years. Cocaine, amphetamines and poly-SUD were
associated with worse symptomatic and functional outcomes from the 1st year of
treatment, persisting over time with higher service utilization
(hospitalization). CONCLUSION: The negative impact attributed to CUD in previous
studies could be partly attributed to methodological flaws, like including
polysubstance abusers among cannabis misusers. However, our investigation
confirmed the negative effect of CUD on outcome. Attention should be paid to
persistent cannabis misusers, since their condition seems to worsen over time,
and to cocaine and amphetamine misusers, in view of their poorer outcome early
during follow-up and high service utilization.
PMID- 28424106
TI - Early developmental influences on self-esteem trajectories from adolescence
through adulthood: Impact of birth weight and motor skills.
AB - While the trajectory of self-esteem from adolescence to adulthood varies from
person to person, little research has examined how differences in early
developmental processes might affect these pathways. This study examined how
early motor skill development interacted with preterm birth status to predict
self-esteem from adolescence through the early 30s. We addressed this using the
oldest known, prospectively followed cohort of extremely low birth weight (<1000
g) survivors (N = 179) and normal birth weight controls (N = 145) in the world,
born between 1977 and 1982. Motor skills were measured using a performance-based
assessment at age 8 and a retrospective self-report, and self-esteem was reported
during three follow-up periods (age 12-16, age 22-26, and age 29-36). We found
that birth weight status moderated the association between early motor skills and
self-esteem. Stable over three decades, the self-esteem of normal birth weight
participants was sensitive to early motor skills such that those with poorer
motor functioning manifested lower self-esteem, while those with better motor
skills manifested higher self-esteem. Conversely, differences in motor skill
development did not affect the self-esteem from adolescence to adulthood in
individuals born at extremely low birth weight. Early motor skill development may
exert differential effects on self-esteem, depending on whether one is born at
term or prematurely.
PMID- 28424108
TI - A systematic review of early modelling studies of Ebola virus disease in West
Africa - CORRIGENDUM.
PMID- 28424109
TI - The Impact of Gender on Complications and Outcomes of Pelvic Fracture.
PMID- 28424107
TI - Early maturation and substance use across adolescence and young adulthood: A
longitudinal study of Finnish twins.
AB - Early maturation, indexed by pubertal development (PD), has been associated with
earlier initiation and greater frequency of adolescent substance use, but this
relationship may be biased by confounding factors and effects that change across
development. Using a population-based Finnish twin sample (N = 3,632
individuals), we conducted twin modeling and multilevel structural equation
modeling of the relationship between PD and substance use at ages 12-22. Shared
environmental factors contributed to early PD and heavier substance use for
females. Biological father absence was associated with early PD for boys but not
girls, and did not account for the relationship between PD and substance use. The
association between early PD and heavier substance use was partially due to
between-family confounds, although early PD appeared to qualitatively alter long
term trajectories for some substances (nicotine), but not others (alcohol).
Mediation by peer and parental factors did not explain this relationship within
families. However, higher peer substance use and lower parental monitoring were
themselves associated with heavier substance use, strengthening the existing
evidence for these factors as targets for prevention/intervention efforts. Early
maturation was not supported as a robust determinant of alcohol use trajectories
in adolescence and young adulthood, but may require longer term follow-up. Subtle
effects of early PD on nicotine and illicit drug use trajectories throughout
adolescence and adulthood merit further investigation.
PMID- 28424110
TI - Native Americans Have an Increased Risk of Major Bile Duct Injury during
Laparoscopic Cholecystectomy: Results from a Statewide Analysis.
PMID- 28424111
TI - Management of Recurrent Invasive Ductal Carcinoma in Transrectus Abdominis
Myocutaneous Flap and Lymphatic Remodeling to the Contralateral Axilla.
PMID- 28424112
TI - Upregulation of CA 19-9 in Complicated Cholecystitis.
PMID- 28424113
TI - Vicarious Contrast Excretion with Prolonged Retention Causing Biliary Colic.
PMID- 28424114
TI - Retroversus Implantation of a Situs Solitus Deceased Donor Liver into a Situs
Inversus Totalis Recipient.
PMID- 28424115
TI - Continuous Abdominal Irrigation for Treatment of Tertiary Peritonitis in the
Immunosuppressed Patient after Solid Organ Transplant: A Novel Approach.
PMID- 28424116
TI - Hyponatremia on Initial Presentation Correlates with Suboptimal Outcomes after
Traumatic Brain Injury.
PMID- 28424117
TI - Damage Control Surgery and the Management of a Cholecystocolic Fistula.
PMID- 28424118
TI - Intussusception in the Adult Population: A Challenge to Surgeons.
PMID- 28424119
TI - The Changing Epidemiology of Diverticulitis in the United States.
PMID- 28424121
TI - Gallbladder Polyps in Children: A Painful Inflammatory Process.
PMID- 28424122
TI - Vascular Complications in Pediatric Port Removal.
PMID- 28424123
TI - A Case of Ingested Dental Prosthesis with Sharp Clasps Successfully Removed
Through Anus Using Part of a Plastic Glove.
PMID- 28424124
TI - Acute Respiratory Distress Syndrome Incidence, But Not Mortality, Has Decreased
Nationwide: A National Trauma Data Bank Study.
AB - Acute respiratory distress syndrome (ARDS) incidence is reported to have
decreased in recent years. However, no large-scale study to date has exclusively
examined ARDS in the critically injured. We sought to examine the national
incidence of ARDS and its associated outcomes exclusively in adult trauma
patients. The National Trauma Data Bank (NTDB) was queried to evaluate the
incidence of ARDS and associated outcomes over a 6-year study period (2007-2012).
Included patients were >=18 years old, with at least one ventilator day, and
complications recorded. ARDS-associated outcomes and complications were also
analyzed. Mean age increased over the study period (48.1-51.4 years, P < 0.003).
ARDS incidence decreased from 21.5 to 8.5 per cent (P < 0.001). Length of stay
(LOS), intensive care unit LOS (ICU LOS), and ventilator days decreased over
time. Mortality increased from 21.3 to 24.9 per cent (P < 0.002). Incidence of
pneumonia and acute kidney injury increased marginally (39.5-40.9% and 11.4
12.3%, respectively). Sepsis trended down from 2007 to 2010, after which
comparable NTDB data were not available. ARDS incidence in mechanically
ventilated adult trauma patients has decreased significantly in recent years. We
theorize this is likely attributable to improved critical care strategies. Unlike
ARDS incidence, mortality in this patient population has not improved despite
these advancements.
PMID- 28424125
TI - Thromboelastography Utilization in Delayed Recurrent Coagulopathy after Severe
Eastern Diamondback Rattlesnake Envenomation.
AB - Venomous snakebites are fairly common in the United States and can present with a
wide range of symptoms. A 48-year-old man presented after Eastern Diamondback
rattlesnake envenomation. His hospital course was complicated by right leg
compartment syndrome and delayed recurrent coagulopathy, requiring multiple doses
of Crotalidae Polyvalent Immune Fab (CroFab) antivenom and transfusions.
Thromboelastography was used as an adjunct to standard coagulation studies in
monitoring his delayed recurrent coagulopathy.
PMID- 28424126
TI - The Novel Use of Resuscitative Endovascular Balloon Occlusion of the Aorta to
Explore a Retroperitoneal Hematoma in a Hemodynamically Unstable Patient.
AB - Balloon occlusion of the aorta was first described by C.W. Hughes in 1954, when
it was used as a tamponade device for three wounded soldiers during the Korean
War suffering from intra-abdominal hemorrhage. Currently, the device is indicated
in trauma patients as a surrogate for resuscitative thoracotomy. Brenner et al.
reported a case series describing the use of resuscitative endovascular balloon
occlusion of the aorta (REBOA) in advanced hemorrhagic shock. Their conclusion
was that "it is a feasible method for proximal aortic control." We describe the
novel use of REBOA before retroperitoneal hematoma exploration in a
hemodynamically unstable patient. Reported is a 19-year-old blunt trauma victim
where REBOA was successfully deployed as a means for proximal arterial control
before a Zone 1 retroperitoneal hematoma exploration. The source of the patient's
hemorrhagic shock was multifactorial: grade V hepatic injury, retrohepatic
inferior vena cava laceration, and right renal vein avulsion with Zone 1
retroperitoneal hematoma. Immediate return of perfusion pressure, as systolic
pressures increased from 50 to 150 mm Hg. Hemodynamic improvements were
accompanied by decreased transfusion and vasopressor requirements. In addition,
the surgeons were able to enter the retroperitoneal hematoma under controlled
conditions. REBOA is an attractive new tool to gain proximal aortic control in
select patients with hemorrhagic shock. It is less morbid, possibly more
efficient, and appears to be more effective than resuscitative thoracotomy. REBOA
is certainly feasible for proximal aortic control before retroperitoneal
exploration, and should be considered in select patients.
PMID- 28424127
TI - Analysis of Mortality in Traumatically Injured Patients Based on Body Mass Index
and Mechanism Reveals Highest Mortality among the Underweight in Comparison with
the Ideal Weight Patients.
AB - The purpose of this study was to evaluate the effect of body mass index (BMI) on
mortality after traumatic injury. The records of patients from 2012 to 2015 were
retrospectively reviewed. The patients were stratified into the following groups
based on admission BMI (kg/m2): underweight (UW) (BMI <19), ideal weight (IW)
(BMI = 19-24.9), overweight (OW) (BMI = 25-29.9), obese (OB) (BMI = 30-39.9), and
morbid obese (MO) (BMI >40). The groups were well matched with no significant
differences in demographics and Injury Severity Score. Morality for the IW group
was compared with the remaining BMI groups. A total of 6049 patients were
identified. In comparison with IW group, the UW mortality was significantly
higher (IW vs UW, 4.1% vs 8.8%, P = 0.001); however, the there was no significant
difference with remaining groups. There was also no significant difference in
mortality between IW and the remaining groups for patients that went directly to
the operating room or for patients that had penetrating trauma (stab wounds and
gunshot wounds). However, for blunt trauma, the mortality was significantly
higher for UW (IW vs UW, 4.3% vs 9.4%, P = 0.001), no different for IW vs OW
(4.3% vs 3.7%, P = 0.3), and significantly lower for IW vs OB (4.3% vs 2.8%, P =
0.04) and for IW vs MO (4.3% vs 1.0%, P = 0.03). After traumatic injuries, it is
the underweight patients (BMI <19) and not the obese, that are at a significantly
higher risk for overall mortality; this difference is especially evident after
blunt trauma where obesity may actually confer a protective role.
PMID- 28424128
TI - Analysis of All-Terrain Vehicle Trauma Data: Implications for Increased
Regulation and Injury Prevention.
AB - To determine the incidence and severity of all-terrain vehicle crashes (ATVCs)
compared with motorcycle crashes (MCCs) in all critically injured patients.
Prospective data were retrospectively reviewed on 1840 patients involved in ATVCs
and MCCs admitted to a rural level one trauma center over 16 years. ATVC patients
(n = 655) were younger (25 vs 38, P < 0.0001), more likely female (20% vs 11%, P
< 0.001), less severely injured (13.5 vs 16, P < 0.0001), had similar Glasgow
Coma Score (13.3 vs 13.4, p = NS), less helmet use (6% vs 69%, P < 0.0001), more
closed head injuries (59.7% vs 54.3%, P < 0.05), more facial injuries (16.9%vs
12.5%, P < 0.05), and lower mortality rate (2.8% vs 5.9%, P < 0.01) compared with
MCC patients (n = 1172). Pediatric patients involved in ATVC were more common
(29.8% vs 4.8%, P < 0.001), had decreased helmet use (12% vs 59%, P < 0.001) and
decreased mortality (3.5% vs 14.3%, P < 0.01). Further injury prevention efforts
regarding helmet use and increased regulations regarding ATVCs are needed to
decrease the morbidity associated with these recreational vehicles.
PMID- 28424129
TI - Hospital Characteristics Affect Consent and Conversion Rates for Potential Organ
Donors.
AB - Consent and conversion rates of potential organ donors in the United States need
to be maximized to match the number of individuals awaiting organ donation.
Studies to date have not focused on characteristics of centers with better
outcomes. We performed an 8-year (2006-2014) retrospective study of our local
organ procurement organization database. We categorized hospitals in our region
as academic centers versus nonacademic centers, trauma centers versus nontrauma
centers, and large (>=400 beds) centers versus small (<400 beds) centers. We also
compared trauma centers with Level I designation to all other centers. Primary
outcomes included consent and conversion rates for potential organ donors. There
were 22,732 referrals to our organ procurement organization that resulted in
1,057 eligible deaths. When comparing academic to nonacademic hospitals, academic
hospitals had higher consent (71% vs 59%, P < 0.0001) and conversion (73% vs 64%,
P = 0.008) rates. Level I trauma centers had better consent and conversion rates
when compared to all other hospitals, 73 versus 55 per cent and 76 versus 61 per
cent respectively, P < 0.0001 for both. The small, academic, trauma centers had
the highest consent and conversion rates, 77 and 78 per cent, respectively, P <
0.0001 for both. Hospital characteristics such as academic involvement, Level I
trauma designation, and size impact consent and conversion rates for potential
organ donors. Small (<400 bed), academic, trauma centers have the highest consent
rates and conversion rates. Factors for success in these institutions should be
examined and applied to assist in improving donor rates across all types of
hospitals.
PMID- 28424130
TI - Invasive Pleomorphic Lobular Histology Is an Adverse Prognostic Factor on
Survival in Patients with Breast Cancer.
AB - Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and
different subtype of classical invasive lobular carcinoma (ILC). This special
variant is characterized by significant cytological atypia and pleomorphism which
differs from the cytological uniformity of ILC. IPLC has been shown to have some
poor prognostic factors such as axillary node metastasis and higher histological
grade which may lead to poor clinical courses including a short relapse time,
increased risk of recurrence and a decreased survival. The aim of this study is
to investigate the clinicopathological characteristics and prognosis of IPLC in
comparison with ILC and also to evaluate if IPLC is a different clinical entity
compared to ILC. A total number of 4418 breast cancer patients treated between
1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively
analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients
diagnosed with pure IPLC. In this present study, clinicopathological
characteristics, disease free survival (DFS) and overall survival (OS) of
patients with ILC and IPLC were compared. This study design is one of the rare
face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased
rate of higher histologic grade, extracapsular extension, lymphovascular invasion
and lower percentage of hormone positivity than those of patients with ILC.
During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence,
5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic
patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of
death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC
group. Patients with IPLC had a worse DFS and OS duration than patients with ILC
(P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a
special breast cancer subtype. This study suggests that IPLC is a distinct
clinical entity with an advanced stage and more aggressive clinical course.
Patients with IPLC reveal poorer prognostic factors such as higher histological
grade, relative lower percentages of hormone positivity, and increased rate of
recurrences resulting in poor clinical outcomes and worse survival. Nowadays, it
is observed that current treatment methods for IPLC do not seem as successful as
in ILC and failed to be effective. Thence, individual therapies including more
aggressive surgery and adjuvant or neoadjuvant chemotherapy even in the earlier
stages of breast cancer should be performed for this distinct variant.
PMID- 28424131
TI - Postoperative Complications Predict 30-Day Readmission in Geriatric General
Surgery Patients.
AB - The Affordable Care Act has placed unplanned patient readmissions under more
scrutiny than ever. Geriatric patients, in particular, suffer a disproportionate
amount of complications from any kind of hospitalization, including readmissions.
This study seeks to identify risk factors in this population that predispose them
to an unplanned readmission within 30 days after index surgery. The National
Surgical Quality Improvement Program database was used to select patients 65
years and older, who underwent general surgery procedures in 2012. Patient
demographics, comorbidities, complications, and readmissions were analyzed. A Cox
regression survivorship model was used for multivariate analysis. A total of 7712
patients were reviewed; 617 patients (8.0%) had an unplanned readmission within
30 days of their operation. Cox regression revealed five different independent
predictors of unplanned readmission within 30 days. They are age [P = 0.009,
hazard ratio (HR) = 1.016, 95% confidence interval (CI) = 1.01-1.03], American
Society of Anesthesiologists Class >2 (P = 0.037, HR = 1.22, CI = 1.024-1.475),
operation time (minutes) (P = 0.001, HR = 1.001, CI = 1.00-1.002), any
complication (P = 0.03, HR = 1.449, CI = 1.33-1.852), and deep vein thrombosis (P
= 0.03, HR = 1.87, CI = 1.31-3.85). Using Cox regression to adjust for patient
length of stay, age, American Society of Anesthesiologists class, any
complication, operation time, and venous thromboembolism all independently
increased the rate of unplanned readmissions. Patients who suffer any
complication or a venous thromboembolism postoperatively are at a particularly
high risk of readmission. These patients should be targeted for increased
inpatient monitoring and included in preventable readmission programs after
discharge.
PMID- 28424132
TI - Outcomes of Recreational Activity-Associated Trauma in Elderly Persons on Blood
Thinning Medications.
AB - With increasing life expectancy, the elderly are participating in recreational
activities traditionally pursued by younger persons. Elderly patients have many
reasons for worse outcomes after trauma, one of which may be the rising use of
anticoagulant and/or antiplatelet medications. This study aimed to determine
whether preinjury use of these agents yielded worse outcomes in geriatric
patients injured during high-impact recreational activities. The National Trauma
Data Bank was reviewed from 2007 to 2010 for patients >=65 years admitted to
Level I or II trauma centers with ICD-9 E-codes for specific mechanisms of
injury. These included motorcycles, bicycles, snowmobiles, all-terrain vehicles,
equestrian, water and alpine skiing, snowboarding, and others. Patients with
preinjury bleeding disorder (BD), including warfarin and clopidogrel use, were
compared with controls via a coarsened exact matching analysis. BD patients (294)
were compared with 3929 controls. Although increased in BD patients, no
significant mortality differences were observed in unmatched or matched analyses.
BD patients yielded greater hospital length of stay (5 vs 4 days, P = 0.020) with
increased odds of receiving five units or more of blood (7.0% vs 2.1%, odds ratio
= 4.7, P < 0.001) and of deep vein thrombosis (7.6% vs 3.8%, odds ratio = 2.1, P
= 0.018). Elderly patients with BD, including warfarin or clopidogrel use, do not
seem to have significantly increased mortality after injury during specified
recreational activities. BD patients had greater hospital length of stay,
transfusion requirements, and deep vein thrombosis rates. These findings may
inform counseling for those taking such medications as to the potential for
adverse outcomes.
PMID- 28424133
TI - Carotid Duplex Ultrasonography: Additional Imaging Is Rarely Necessary for
Appropriate Treatment Planning for Carotid Artery Disease.
AB - This study was conducted to determine the utility of multiple imaging studies (CT
angiography, magnetic resonance angiography, and/or conventional angiography), in
addition to duplex ultrasonography (DU), in evaluating patients with carotid
stenosis. A retrospective case series was conducted of patients with carotid
stenosis who underwent DU alone or DU plus additional imaging. Concordance
between DU and additional imaging and the effect on treatment plan was evaluated.
Two hundred patients with carotid stenosis were evaluated. Sixty-four had DU plus
additional imaging. Sixty-two of the patients (96.9%) had no change in treatment
due to additional imaging. Only 2 of the 64 patients (3.1%) with additional
imaging had a change in treatment plan. In conclusion, additional imaging, beyond
DU, is rarely necessary for treatment planning in patients with carotid disease.
PMID- 28424134
TI - Six-Year Experience of Outpatient Total and Completion Thyroidectomy at a Single
Academic Institution.
AB - Outpatient thyroidectomy has become slowly accepted with various published
reports predominantly examining partial or subtotal thyroidectomy. Concerns
regarding the safety of outpatient total and completion thyroidectomy remain,
especially with regard to vocal fold paralysis, hypocalcemia, and catastrophic
hematoma. We aimed to evaluate the safety of outpatient thyroid surgery in a
large cohort by retrospectively comparing outcomes in those who underwent
outpatient (n = 251) versus inpatient (n = 291) completion or total thyroidectomy
between February 2009 and February 2015. Outpatient completion and total
thyroidectomy had lower rates of temporary hypocalcemia (6% vs 24.4%; P < 0.001)
and no significant difference in rates of return to emergency department (1.2% vs
1.4%), hematoma formation (0.8% vs 0.7%), temporary (2% vs 4.1%) or permanent
(0.4% vs 0.7%) vocal fold paralysis, or permanent hypocalcemia (0.4% vs 0%)
compared with the inpatient group. Outpatients requiring calcium replacement had
shorter duration of postoperative calcium supplementation (44.4 +/- 59.3 days vs
63.3 +/- 94.4 days; P < 0.001). Our data demonstrate similar safety in outpatient
and inpatient total and completion thyroidectomy.
PMID- 28424135
TI - Bladder Fill after Laparoscopic Inguinal Hernia Repair Reduces Time to Discharge.
AB - Laparoscopic inguinal herniorrhaphy (LIH) has a relatively high risk of urinary
retention. Bladder dysfunction may delay discharge after LIH. We hypothesized
that filling the bladder before Foley catheter removal decreases time to
discharge (TTD) after LIH. A secondary aim was to determine incidence of
postoperative urinary retention (POUR) after bladder fill (BF). We reviewed a
consecutive series of total extraperitoneal and transabdominal preperitoneal LIH
procedures performed by a single surgeon at our institution from 2010 to 2013.
All patients were catheterized during LIH, and selected patients received a 200
mL saline BF before Foley catheter removal. Patients were required to void >250
mL before discharge. TTD and incidence of POUR were compared between the BF and
no-BF groups. A total of 161 LIH cases were reviewed. BF was performed in 89/161
(55%) of cases. TTD was significantly shorter in the BF versus the no-BF group
(222 vs 286 minutes, respectively; P < 0.01). Patient and operative
characteristics were similar between the BF and no-BF groups (P > 0.05).
Incidence of POUR in the BF and the no-BF group was 10.1 and 16.7 per cent,
respectively; however, this difference was not significant (P = 0.22). No
postoperative urinary tract infection occurred in either group. In conclusions,
postoperative BF significantly reduces TTD after LIH. Further studies may help to
determine whether shorter postanesthesia care unit time and lower POUR rates
associated with BF can lower LIH procedural costs and increase patient
satisfaction.
PMID- 28424136
TI - The Role of Doctors and Patients in Appendicitis Perforation.
AB - In this study, we aimed to determine factors that cause appendix perforations and
to identify the role of physicians and patients in contributing to the cause of
these perforations. This study was conducted between April 2010 and May 2015 and
included 64 patients with perforated appendicitis. Patients' medical records were
examined for factors that might have contributed to perforation, and the roles of
patients and physicians in perforation appendicitis were evaluated. The
perforation rate of patients with appendicitis was 16.0 per cent. The average
duration from symptom onset to hospital admission was 4.4 days (29 patients were
admitted to hospital within two days, 35 were admitted later). In total, 38
patients had visited a different hospital before admission. Furthermore, six out
of 26 patients who had not visited any other hospital had consumed analgesics.
Factors contributing to appendix perforation included misdiagnosis at the
patient's initial visit (56.0%), delayed admission to hospital (11.0%), and use
of analgesics (9.0%). The cause of perforation was mostly physician-related in
children and adults, and patient-related in older adults.
PMID- 28424137
TI - Improvement of Treatment Outcomes after Implementation of a Massive Transfusion
Protocol: A Level I Trauma Center Experience.
AB - We assessed the effectiveness of the implementation of an institutional massive
transfusion protocol (MTP) for resuscitation with a 1:1:1 transfusion ratio of
packed red blood cell (PRBC), fresh frozen plasma, and platelet units. In a Level
I trauma center database, all trauma admissions (2004-2012) that received massive
transfusions (>=10 units PRBCs in the first 24 hours) were reviewed
retrospectively. Demographic data, transfusion ratios, and outcomes were compared
before (PRE) and after (POST) MTP implementation in May 2008. Age, sex, and
mechanism of injury were similar between 239 PRE and 208 POST trauma patients
requiring massive transfusion. Transfusion ratios of fresh frozen plasma:PRBC and
platelet:PRBC increased after MTP implementation. Among survivors, MTP
implementation shortened hospital length of stay from 31 to 26 days (P = 0.04)
and intensive care unit length of stay from 31 to 26 days (P = 0.02). Linear
regression identified treatment after (versus before) implementation of MTP as an
independent predictor of decreased ventilator days after adjusting for age,
Glasgow Coma Scale, and chest Abbreviated Injury Score (P < 0.0001). Modest
improvement in ratios likely does not account for all significant improvements in
outcomes. Implementing a standardized protocol likely impacts automation,
efficiency, and/or timeliness of product delivery.
PMID- 28424138
TI - Comparative Analysis of the Paravertebral Analgesic Pump Catheter with the
Epidural Catheter in Elderly Trauma Patients with Multiple Rib Fractures.
AB - Presently, trauma guidelines recommend epidural analgesia as the optimal modality
of pain relief from rib fractures. They are not ideally suited for elderly trauma
patients and have disadvantages including bleeding risk. The paravertebral
analgesic pump (PVP) eliminates such disadvantages and includes ease of placement
in the trauma setting. This study compares pain control in patients treated by
EPI versus PVP. This is a retrospective, historical cohort study comparing two
methods of pain management in the trauma setting. Before 2010, patients who had
epidural catheters (EPI) placed for pain control were compared with patients
after 2010 in which the PVP was used. All patients had multiple rib fractures as
diagnosed by CT scan. Analysis was adjusted for age, number of fractures, and
comorbid conditions. Multiple linear regression analysis was conducted to compare
average reported pain. A total of 110 patients, 31 PVP and 79 epidural catheters,
were included in the study. Overall mean age was 65 years. The mean Injury
Severity Score was 12.0 (EPI) and 11.1 (PVP). Mean number rib fractures was 4.29
(EPI) and 4.71 (PVP). PVP was associated with a 30 per cent greater decrease in
pain than that seen with EPI (6.0-1.9 vs 6.4-3.4). After controlling for age,
Injury Severity Score, and number of rib fractures, there were no differences in
intensive care unit or total length of stay (P = 0.35) or in pain score (3.76 vs
3.56, P = 0.64). In conclusion, the PVP compares well with epidural analgesia in
older trauma patients yet is safe, well tolerated, and easily inserted.
PMID- 28424139
TI - Lethal Trauma Pulmonary Embolism Is a Black Swan Event in Patients at Risk for
Deep Vein Thrombosis: An Evidence-Based Review.
AB - We delineated the incidence of trauma patient pulmonary embolism (PE) and risk
conditions by performing a systematic literature review of those at risk for deep
vein thrombosis (DVT). The PE proportion was 1.4 per cent (95% confidence
interval = 1.2-1.6) in at-risk patients. Of 10 conditions, PE was only associated
with increased age (P < 0.01) or leg injury (P < 0.01; risk ratio = 1.6). As
lower extremity DVT (LEDVT) proportions increased, mortality proportions (P =
0.02) and hospital stay (P = 0.0002) increased, but PE proportions did not (P =
0.13). LEDVT was lower with chemoprophylaxis (CP) (4.9%) than without CP (19.1%;
P < 0.01). PE was lower with CP (1.0%) than without CP (2.2%; P = 0.0004).
Mortality was lower with CP (6.6%) than without CP (11.6%; P = 0.002). PE was
similar with (1.2%) and without (1.9%; P = 0.19) mechanical prophylaxis (MP).
LEDVT was lower with MP (8.5%) than without MP (12.2%; P = 0.0005). PE
proportions were similar with (1.3%) and without (1.5%; P = 0.24) LEDVT
surveillance. Mortality was higher with LEDVT surveillance (7.9%) than without
(4.8%; P < 0.01). A PE mortality of 19.7 per cent (95% confidence interval = 18
22) * a 1.4 per cent PE proportion yielded a 0.28 per cent lethal PE proportion.
As PE proportions increased, mortality (P = 0.52) and hospital stay (P = 0.13)
did not. Of 176 patients with PE, 76 per cent had no LEDVT. In trauma patients at
risk for DVT, PE is infrequent, has a minimal impact on outcomes, and death is a
black swan event. LEDVT surveillance did not improve outcomes. Because PE was not
associated with LEDVT and most patients with PE had no LEDVT, preventing,
diagnosing, and treating LEDVT may be ineffective PE prophylaxis.
PMID- 28424140
TI - Impact of Multimodality Pain Regimens on Elective Colorectal Surgery Outcomes.
AB - Trials of enhanced recovery programs suggest that multimodality pain regimens
improve outcomes after colorectal surgery. We sought to determine whether
patients receiving postoperative multimodality pain regimens would have shorter
lengths of stay without an associated increase in readmission rate as compared to
those receiving opioid-based pain regimens. Retrospective cohort study of adults
who underwent elective colorectal surgery between January 1, 2006, and December
31, 2012, in a national hospital network participating in the Premier Perspective
database. Patients were grouped into multimodality or opioid-based using
postoperative medication charges. Primary outcome measures included length of
stay and 30-day readmission rate. Among 91,936 patients, 38 per cent received
multimodality pain regimens and 61 per cent received opioid-based regimens. After
adjustment for patient and surgical characteristics, there was no difference in
length of stay or cost, odds of readmission were 1.2 (95% confidence interval =
1.2-1.3, P < 0.001), and odds of mortality were 0.8 (95% confidence interval =
0.6-0.9, P < 0.001) in the multimodality group compared to nonopioid sparing. Our
results were consistent in secondary analyses using propensity matching. Fewer
than half of patients undergoing elective colorectal surgery in our cohort
received multimodality pain regimens, and receipt of these medications was
associated with mixed benefits in terms of length of stay, readmission, and
mortality.
PMID- 28424141
TI - Can Parathormon Levels after Ipsilateral Lobectomy Predict Postoperative
Hypocalcemia in Patients Undergoing Total Thyroidectomy?
AB - The purpose of this study was to investigate the relationship between the serum
parathormone (PTH) levels measured after completion of hemithyroidectomy on the
first side during total thyroidectomy and the postoperative hypocalcemia. The
patients were divided into two groups, as those who demonstrated a decrease in
PTH levels measured after completion of hemithyroidectomy of the first side
(Group 1, n = 43) and those who did not demonstrate a decrease in PTH levels
(Group 2, n = 24). The serum PTH levels were measured just before the incision
(PTHi), when the hemithyroidectomy stage had been completed (PTHht), at the end
of the operation (PTHtt), and at the postoperative 24th hour (PTH24hr). The serum
total calcium (Ca2+) levels were also measured. The median percentage differences
in PTHtt levels based on basal PTHi levels of Groups 1 and 2 were -60.6 and -15.7
per cent, respectively, P = 0.001. The frequency of postoperative biochemical
hypocalcemia was higher in Group 1, P < 0.05. It was determined that a 10 per
cent or higher decrease in PTHht levels in Group 1 could predict biochemical
hypocalcemia at the postoperative 24th hour. In conclusions, postoperative
hypocalcemia is seen more frequent in patients with a decrease of PTHht during
total thyroidectomy. A decrease of 10 per cent in PTHht levels measured after
ipsilateral lobectomy and a 62 per cent or higher decrease in PTHtt levels
measured in the end of the total thyroidectomy could be helpful for prediction of
postoperative hypocalcemia in these patients.
PMID- 28424142
TI - Advance care planning, culture and religion: an environmental scan of Australian
based online resources.
AB - Objectives Culture and religion are important in advance care planning (ACP), yet
it is not well understood how this is represented in ACP online resources. The
aim of the present study was to identify the availability of Australian-based ACP
websites and online informational booklets containing cultural and religious
information. Methods An environmental scanning framework was used with a Google
search conducted from 30 June 2015 to 5 July 2015. Eligible Australian-based ACP
websites and online informational booklets were reviewed by two analysts (APS &
PM) for information pertaining to at least one culture or religion. Common
characteristics were agreed upon and tabulated with narrative description.
Results Seven Australian-based ACP websites were identified with varying degrees
of cultural and religious information. Seven Australian-based ACP informational
booklets were identified addressing culture or religion, namely of Aboriginal and
Torres Strait Islander (n=5), Sikh (n=1) and Italian (n=1) communities. Twenty
one other online resources with cultural and religious information were
identified, developed within the context of health and palliative care.
Conclusions There is no comprehensive Australian-based ACP website or
informational booklet supporting ACP across several cultural and religious
contexts. Considering Australia's multicultural and multifaith population, such a
resource may be beneficial in increasing awareness and uptake of ACP. What is
known about the topic? Health professionals and consumers frequently use the
Internet to find information. Non-regulation has resulted in the proliferation of
ACP online resources (i.e. ACP websites and online informational booklets).
Although this has contributed to raising awareness of ACP, the availability of
Australian-based ACP online resources with cultural and religious information is
not well known. What does this paper add? This paper is the first to use an
environmental scanning methodology to identify Australian-based ACP websites and
online informational booklets with cultural and religious information. What are
the implications for practitioners? The results of this environmental scan
present the availability of Australian-based ACP websites and online
informational booklets containing cultural and religious information. A thorough
understanding may assist in identifying gaps for future ACP project planning and
policy objectives, consistent with meeting cultural and religious needs. This may
be beneficial for health professionals, consumers, health associations,
organisations and government policy makers concerned with ACP.
PMID- 28424143
TI - Correlates of sexually transmissible infection testing among a sample of at-risk
young Australians.
AB - Annual chlamydia testing is recommended for all sexually active Australians aged
15-29 years; however, the testing rate is below recommended levels. Three surveys
at a Melbourne music festival were conducted over 2012-14 to identify correlates
of sexually transmissible infection (STI) testing among young people at risk of
STIs. In total, 3588 participants were recruited; 72% reported having sex in the
past year. Based on sexual behaviours, 38% of sexually active participants were
classified as at risk of contracting STIs. In the past year, at-risk participants
had significantly higher odds of reporting a STI test (37%) than participants
classified as not at risk (24%) (OR=1.9; CI=1.6-2.3). Among at-risk participants,
correlates of STI testing in the past year included being aged 20-24 years,
visiting a GP, higher knowledge levels, earlier sexual debut and reporting more
than five lifetime partners. Testing rates in our sample did not meet levels
required to reduce chlamydia prevalence. However, the testing rate was higher in
at-risk participants than participants who were not at risk. Future programs
aiming to increase chlamydia testing should improve knowledge and promote the
importance of testing after risk exposure, particularly among 16- to 19-year
olds.
PMID- 28424144
TI - Expertise and infrastructure capacity impacts acute coronary syndrome outcomes.
AB - Objective Effective translation of evidence to practice may depend on systems of
care characteristics within the health service. The present study evaluated
associations between hospital expertise and infrastructure capacity and acute
coronary syndrome (ACS) care as part of the SNAPSHOT ACS registry. Methods A
survey collected hospital systems and process data and our analysis developed a
score to assess hospital infrastructure and expertise capacity. Patient-level
data from a registry of 4387 suspected ACS patients enrolled over a 2-week period
were used and associations with guideline care and in-hospital and 6-, 12- and 18
month outcomes were measured. Results Of 375 participating hospitals, 348 (92.8%)
were included in the analysis. Higher expertise was associated with increased
coronary angiograms (440/1329; 33.1%), 580/1656 (35.0%) and 609/1402 (43.4%) for
low, intermediate and high expertise capacity respectively; P<0.001) and the
prescription of guideline therapies observed a tendency for an association with
(531/1329 (40.0%), 733/1656 (44.3%) and 603/1402 (43.0%) for low, intermediate
and high expertise capacity respectively; P=0.056), but not rehabilitation
(474/1329 (35.7%), 603/1656 (36.4%) and 535/1402 (38.2%) for low, intermediate
and high expertise capacity respectively; P=0.377). Higher expertise capacity was
associated with a lower incidence of major adverse events (152/1329 (11.4%),
142/1656 (8.6%) and 149/149 (10.6%) for low, intermediate and high expertise
capacity respectively; P=0.026), as well as adjusted mortality within 18 months
(low vs intermediate expertise capacity: odds ratio (OR) 0.79, 95% confidence
interval (CI) 0.58-1.08, P=0.153; intermediate vs high expertise capacity: OR
0.64, 95% CI 0.48-0.86, P=0.003). Conclusions Both higher-level expertise in
decision making and infrastructure capacity are associated with improved evidence
translation and survival over 18 months of an ACS event and have clear healthcare
design and policy implications. What is known about the topic? There are
comprehensive guidelines for treating ACS patients, but Australia and New Zealand
registry data reveal substantial gaps in delivery of best practice care across
metropolitan, regional, rural and remote health services, raising questions of
equity of access and outcome. Greater mortality and morbidity gains can be
achieved by increasing the application of current evidence-based therapies than
by developing new therapy innovations. Health service system characteristics may
be barriers or enablers to the delivery of best practice care and need to be
identified and evaluated for correlations with performance indicators and
outcomes in order to improve health service design. What does this paper add?
This study measures two system characteristics, namely expertise and
infrastructure, evaluating the relationship with ACS guideline application and
clinical outcomes in a large and diverse cohort of Australian and New Zealand
hospitals. The study identifies decision-making expertise and infrastructure
capacity, to a lesser degree, as enabling characteristics to help improve patient
outcomes. What are the implications for practitioners? In the design of health
services to improve access and equity, expertise must be preserved. However, it
is difficult to have experienced personnel at the bedside no matter where the
health service, and engineering innovative systems and processes of care to
facilitate delivery of expertise should be considered.
PMID- 28424145
TI - 'We didn't have to dance around it': opt-out HIV testing among homeless and
marginalised patients.
AB - This study explored opt-out HIV testing in an Australian general practice. The
aims were to: (1) determine the effect of the opt-out approach on the number of
HIV tests performed; and (2) explore the acceptability of opt-out HIV testing
from the healthcare providers' perspective. A prospective mixed-methods study of
opt-out HIV testing over a 2-year period (March 2014-March 2016) was conducted.
Implementation was based on a theoretical framework that was developed
specifically for this study. The setting was Homeless Healthcare, a health
service in Perth, Western Australia. The number of HIV tests conducted during the
control year (usual practice) was compared with the intervention year (opt-out
testing). After the intervention, the healthcare providers (n=8) were interviewed
about their experiences with opt-out HIV testing. Directed content analysis was
used to explore the qualitative data. HIV testing rates were low during both the
control year and the intervention year (315 HIV tests (12% of the patient cohort)
and 344 HIV tests (10%) respectively). Opt-out HIV testing was feasible and
acceptable to the participating healthcare providers. Other health services could
consider opt-out HIV testing for their patients to identify people with
undiagnosed infections and sustain Australia's low HIV prevalence.
PMID- 28424146
TI - Excess all-cause and influenza-attributable mortality in Europe, December 2016 to
February 2017.
AB - Since December 2016, excess all-cause mortality was observed in many European
countries, especially among people aged >= 65 years. We estimated all-cause and
influenza-attributable mortality in 19 European countries/regions. Excess
mortality was primarily explained by circulation of influenza virus A(H3N2). Cold
weather snaps contributed in some countries. The pattern was similar to the last
major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in
line with the early influenza season start.
PMID- 28424147
TI - Treatment of Leukoencephalopathy With Calcifications and Cysts With Bevacizumab.
AB - BACKGROUND: Leukoencephalopathy with calcifications and cysts is a rare,
autosomal recessive cerebral microangiopathy that causes progressive white matter
disease, calcifications, and cysts within the brain. It is typically associated
with slowly progressive psychomotor regression, seizures, and movement disorders.
Although leukoencephalopathy with calcifications and cysts affects only the
central nervous system, it demonstrates remarkable neuropathologic and radiologic
overlap with Coats plus, a disorder of small vessels of the brain, eyes,
gastrointestinal tract, and bone. Coats disease without extraocular involvement,
a genetically distinct disorder from Coats plus, is characterized by retinal
telangiectasias and exudative retinopathy, accompanied by neovascularization.
Inhibition of vascular endothelial growth factor (VEGF) signaling with the
monoclonal anti-VEGF antibody bevacizumab can improve retinal edema and exudates
in Coats disease. Given these observations, we reasoned that VEGF inhibition
might also be effective in treating leukoencephalopathy with calcifications and
cysts and Coats plus, neither of which has any known therapy. METHODS: We treated
an 18-year-old man with leukoencephalopathy with calcifications and cysts using
biweekly infusions of the VEGF inhibitor bevacizumab for more than one year and
performed clinical examinations and brain imaging at three month intervals.
RESULTS: After treatment for more than one year, the patient showed improved
bradykinesia and range of motion, and brain magnetic resonance imaging
demonstrated a marked reduction in cyst volume and white matter lesions.
CONCLUSIONS: Further studies in a cohort of patients are warranted to investigate
the efficacy of VEGF inhibition as a treatment for leukoencephalopathy with
calcifications and cysts.
PMID- 28424148
TI - Evidence-based deprescribing of proton pump inhibitors in long-term care.
PMID- 28424151
TI - Parents against prohibition: campaigning for drug law reform.
PMID- 28424149
TI - Comparative Safety of Sulfonylurea and Metformin Monotherapy on the Risk of Heart
Failure: A Cohort Study.
AB - BACKGROUND: Medications that impact insulin sensitivity or cause weight gain may
increase heart failure risk. Our aim was to compare heart failure and
cardiovascular death outcomes among patients initiating sulfonylureas for
diabetes mellitus treatment versus metformin. METHODS AND RESULTS: National
Veterans Health Administration databases were linked to Medicare, Medicaid, and
National Death Index data. Veterans aged >=18 years who initiated metformin or
sulfonylureas between 2001 and 2011 and whose creatinine was <1.4 (females) or
1.5 mg/dL (males) were included. Each metformin patient was propensity score
matched to a sulfonylurea initiator. The outcome was hospitalization for acute
decompensated heart failure as the primary reason for admission or a
cardiovascular death. There were 126 867 and 79 192 new users of metformin and
sulfonylurea, respectively. Propensity score matching yielded 65 986 per group.
Median age was 66 years, and 97% of patients were male; hemoglobin A1c 6.9% (6.3,
7.7); body mass index 30.7 kg/m2 (27.4, 34.6); and 6% had heart failure history.
There were 1236 events (1184 heart failure hospitalizations and 52 cardiovascular
deaths) among sulfonylurea initiators and 1078 events (1043 heart failure
hospitalizations and 35 cardiovascular deaths) among metformin initiators. There
were 12.4 versus 8.9 events per 1000 person-years of use (adjusted hazard ratio
1.32, 95%CI 1.21, 1.43). The rate difference was 4 heart failure hospitalizations
or cardiovascular deaths per 1000 users of sulfonylureas versus metformin
annually. CONCLUSIONS: Predominantly male patients initiating treatment for
diabetes mellitus with sulfonylurea had a higher risk of heart failure and
cardiovascular death compared to similar patients initiating metformin.
PMID- 28424152
TI - Acute appendicitis.
PMID- 28424155
TI - Active commuting is beneficial for health.
PMID- 28424154
TI - Association between active commuting and incident cardiovascular disease, cancer,
and mortality: prospective cohort study.
AB - Objective To investigate the association between active commuting and incident
cardiovascular disease (CVD), cancer, and all cause mortality.Design Prospective
population based study. Setting UK Biobank.Participants 263 450 participants (106
674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The
exposure variable was the mode of transport used (walking, cycling, mixed mode v
non-active (car or public transport)) to commute to and from work on a typical
day.Main outcome measures Incident (fatal and non-fatal) CVD and cancer, and
deaths from CVD, cancer, or any causes.Results 2430 participants died (496 were
related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile
range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In
maximally adjusted models, commuting by cycle and by mixed mode including cycling
were associated with lower risk of all cause mortality (cycling hazard ratio
0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76,
0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001;
mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling
0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001).
Commuting by cycling and walking were associated with a lower risk of CVD
incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99,
P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45
to 0.91, P=0.01). No statistically significant associations were observed for
walking commuting and all cause mortality or cancer outcomes. Mixed mode
commuting including walking was not noticeably associated with any of the
measured outcomes.Conclusions Cycle commuting was associated with a lower risk of
CVD, cancer, and all cause mortality. Walking commuting was associated with a
lower risk of CVD independent of major measured confounding factors. Initiatives
to encourage and support active commuting could reduce risk of death and the
burden of important chronic conditions.
PMID- 28424156
TI - Kiran Patel: Eyes on the front line.
PMID- 28424157
TI - Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and
young adults in Sweden.
AB - Objective To examine the relation between childhood adversity, the role of school
performance, and childhood psychopathology and the risk of suicide.Design Cohort
study of register based indicators of childhood adversity (at ages 0-14)
including death in the family (suicide analysed separately), parental substance
abuse, parental psychiatric disorder, substantial parental criminality, parental
separation/single parent household, receipt of public assistance, and residential
instability.Setting Swedish medical birth register and various Swedish population
based registers.Participants 548 721 individuals born 1987-91.Main outcome
measures Estimates of suicide risk at ages 15-24 calculated as incidence rate
ratios adjusted for time at risk and confounders.Results Adjusted incidence rate
ratios for the relation between childhood adversity and suicide during
adolescence and young adulthood ranged from 1.6 (95% confidence interval 1.1 to
2.4) for residential instability to 2.9 (1.4 to 5.9) for suicide in the family.
There was a dose-response relation between accumulating childhood adversity and
risk: 1.1 (0.9 to 1.4) for those exposed to one adversity and 1.9 (1.4 to 2.5)
and 2.6 (1.9 to 3.4) for those exposed to two and three or more adversities,
respectively. The association with increased risk of suicide remained even after
adjustment for school performance and childhood psychopathology.Conclusion
Childhood adversity is a risk factor for suicide in adolescence and young
adulthood, particularly accumulated adversity. These results emphasise the
importance of understanding the social mechanisms of suicide and the need for
effective interventions early in life, aiming to alleviate the risk in
disadvantaged children.
PMID- 28424158
TI - Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping.
AB - Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in
mice and other model organisms. Modifications of traditional gene trap cassettes,
including addition of conditional features in the form of Flip-excision (FlEx)
arrays to enable directional gene trap cassette inversions by Cre and Flpe site
specific recombinases, greatly enhanced their experimental potential. By taking
advantage of these conditional gene trap cassettes, we developed a generic
strategy for generating conditional mutations and validated this strategy in mice
carrying a multipurpose allele of the Prdm16 transcription factor gene. We
demonstrate that the gene trap insertion creates a null mutation replicating the
Pierre Robin sequence-type cleft palate phenotype of other Prdm16 mutant mice.
Consecutive breeding to Flpe and Emx1IREScre deleter mice spatially restricted
Prdm16 loss to regions of the forebrain expressing the homeobox gene Emx1,
demonstrating the utility of the technology for the analysis of tissue-specific
gene functions.
PMID- 28424159
TI - Prolonged Elimination of Negative Feedback Control Mechanisms Along the Insulin
Signaling Pathway Impairs beta-Cell Function In Vivo.
AB - Cellular stress and proinflammatory cytokines induce phosphorylation of insulin
receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-I
signaling. We therefore examined the effects of mutation of five "inhibitory" Ser
phosphorylation sites on IRS2 function in transgenic mice that overexpress,
selectively in pancreatic beta-cells, either wild-type (WT) or a mutated IRS2
protein (IRS25A). Islets size, number, and mRNA levels of catalase and superoxide
dismutase were increased, whereas those of nitric oxide synthase were decreased,
in 7- to 10-week-old IRS25A-beta mice compared with IRS2WT-beta mice. However,
glucose homeostasis and insulin secretion in IRS25A-beta mice were impaired when
compared with IRS2WT-beta mice or to nontransgenic mice. This was associated with
reduced mRNA levels of Glut2 and islet beta-cell transcription factors such as
Nkx6.1 and MafA Similarly, components mediating the unfolded protein response
were decreased in islets of IRS25A-beta mice in accordance with their decreased
insulin secretion. The beneficial effects of IRS25A on beta-cell proliferation
and beta-cell transcription factors were evident only in 5- to 8-day-old mice.
These findings suggest that elimination of inhibitory Ser phosphorylation sites
of IRS2 exerts short-term beneficial effects in vivo; however, their sustained
elimination leads to impaired beta-cell function.
PMID- 28424160
TI - Heterogeneous Nuclear Ribonucleoprotein F Stimulates Sirtuin-1 Gene Expression
and Attenuates Nephropathy Progression in Diabetic Mice.
AB - We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP
F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db).
Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans
with T2D were also studied. The db/db mice developed hyperglycemia, oxidative
stress, and nephropathy at age 20 weeks compared with their db/m littermates.
These abnormalities, with the exception of hyperglycemia, were attenuated in
db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their
RPTCs. Sirtuin-1, Foxo3alpha, and catalase expression were significantly
decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In
vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3alpha with
downregulation of acetylated p53 expression and prevented downregulation of
Sirtuin-1 and Foxo3alpha expression in IRPTCs by high glucose plus palmitate.
Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of
Foxo3alpha and downregulation of acetylated p53 expression. hnRNP F stimulated
Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter.
Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F,
SIRTUIN-1, and FOXO3alpha than nondiabetic kidneys. Our results demonstrate that
hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation
of Sirtuin-1 expression and signaling in diabetes.
PMID- 28424161
TI - Response and progression on midostaurin in advanced systemic mastocytosis: KIT
D816V and other molecular markers.
AB - In advanced systemic mastocytosis (advSM), disease evolution is often triggered
by KIT mutations (D816V in >80% of cases) and by additional mutations (eg, in
SRSF2, ASXL1, and/or RUNX1 [S/A/Rpos in >60% of cases]). In a recently reported
phase 2 study, midostaurin, a multikinase/KIT inhibitor, demonstrated an overall
response rate (ORR) of 60% in advSM but biomarkers predictive of response are
lacking. We evaluated the impact of molecular markers at baseline and during
follow-up in 38 midostaurin-treated advSM patients. The median overall survival
(OS) was 30 months (95% confidence interval, 6-54) from start of midostaurin. ORR
and OS were significantly different between S/A/Rneg (n = 12) and S/A/Rpos (n =
23) patients (ORR: 75% vs 39%, P = .04; OS: P = .01, HR 4.5 [1.3-16.2]).
Depending on the relative reduction of the KIT D816V expressed allele burden
(EAB) at month 6, patients were classified as KIT responders (>=25%, n = 17) or
KIT nonresponders (<25%, n = 11). In univariate analyses at month 6, reduction of
KIT D816V EAB >=25%, tryptase >=50%, and alkaline phosphatase >=50% were
significantly associated with improved OS. In multivariate analysis, only KIT
D816V EAB reduction >=25% remained an independent on-treatment marker for
improved OS (P = .004, HR 6.8 [1.8-25.3]). Serial next-generation sequencing
analysis of 28 genes in 16 patients revealed acquisition of additional mutations
or increasing variant allele frequency in K/NRAS, RUNX1, IDH2, or NPM1 associated
with progression in 7 patients. In midostaurin-treated advSM patients, the
complexity and dynamics of mutational profiles significantly affect response,
progression, and prognosis.
PMID- 28424162
TI - Pembrolizumab in patients with CLL and Richter transformation or with relapsed
CLL.
AB - Chronic lymphocytic leukemia (CLL) patients progressed early on ibrutinib often
develop Richter transformation (RT) with a short survival of about 4 months.
Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to
inhibit immune surveillance in CLL. This phase 2 study was designed to test the
efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a
dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five
patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell
lymphoma) patients were enrolled, and 60% received prior ibrutinib. Objective
responses were observed in 4 out of 9 RT patients (44%) and in 0 out of 16 CLL
patients (0%). All responses were observed in RT patients who had progression
after prior therapy with ibrutinib. After a median follow-up time of 11 months,
the median overall survival in the RT cohort was 10.7 months, but was not reached
in RT patients who progressed after prior ibrutinib. Treatment-related grade 3 or
above adverse events were reported in 15 (60%) patients and were manageable.
Analyses of pretreatment tumor specimens from available patients revealed
increased expression of PD-ligand 1 (PD-L1) and a trend of increased expression
in PD-1 in the tumor microenvironment in patients who had confirmed responses.
Overall, pembrolizumab exhibited selective efficacy in CLL patients with RT. The
results of this study are the first to demonstrate the benefit of PD-1 blockade
in CLL patients with RT, and could change the landscape of therapy for RT
patients if further validated. This trial was registered at
www.clinicaltrials.gov as #NCT02332980.
PMID- 28424163
TI - Clinical significance of somatic mutation in unexplained blood cytopenia.
AB - Unexplained blood cytopenias, in particular anemia, are often found in older
persons. The relationship between these cytopenias and myeloid neoplasms like
myelodysplastic syndromes is currently poorly defined. We studied a prospective
cohort of patients with unexplained cytopenia with the aim to estimate the
predictive value of somatic mutations for identifying subjects with, or at risk
of, developing a myeloid neoplasm. The study included a learning cohort of 683
consecutive patients investigated for unexplained cytopenia, and a validation
cohort of 190 patients referred for suspected myeloid neoplasm. Using granulocyte
DNA, we looked for somatic mutations in 40 genes that are recurrently mutated in
myeloid malignancies. Overall, 435/683 patients carried a somatic mutation in at
least 1 of these genes. Carrying a somatic mutation with a variant allele
frequency >=0.10, or carrying 2 or more mutations, had a positive predictive
value for diagnosis of myeloid neoplasm equal to 0.86 and 0.88, respectively.
Spliceosome gene mutations and comutation patterns involving TET2, DNMT3A, or
ASXL1 had positive predictive values for myeloid neoplasm ranging from 0.86 to
1.0. Within subjects with inconclusive diagnostic findings, carrying 1 or more
somatic mutations was associated with a high probability of developing a myeloid
neoplasm during follow-up (hazard ratio = 13.9, P < .001). The predictive values
of mutation analysis were confirmed in the independent validation cohort. The
findings of this study indicate that mutation analysis on peripheral blood
granulocytes may significantly improve the current diagnostic approach to
unexplained cytopenia and more generally the diagnostic accuracy of myeloid
neoplasms.
PMID- 28424164
TI - Hypoxic adaptation of leukemic cells infiltrating the CNS affords a therapeutic
strategy targeting VEGFA.
PMID- 28424167
TI - Rethinking the regulation of l-carnitine transport in skeletal muscle cells.
Focus on "Multiple AMPK activators inhibit l-carnitine uptake in C2C12 skeletal
muscle myotubes".
PMID- 28424165
TI - Suppression of B-cell development genes is key to glucocorticoid efficacy in
treatment of acute lymphoblastic leukemia.
AB - Glucocorticoids (GCs), including dexamethasone (dex), are a central component of
combination chemotherapy for childhood B-cell precursor acute lymphoblastic
leukemia (B-ALL). GCs work by activating the GC receptor (GR), a ligand-induced
transcription factor, which in turn regulates genes that induce leukemic cell
death. Which GR-regulated genes are required for GC cytotoxicity, which pathways
affect their regulation, and how resistance arises are not well understood. Here,
we systematically integrate the transcriptional response of B-ALL to GCs with a
next-generation short hairpin RNA screen to identify GC-regulated "effector"
genes that contribute to cell death, as well as genes that affect the sensitivity
of B-ALL cells to dex. This analysis reveals a pervasive role for GCs in
suppression of B-cell development genes that is linked to therapeutic response.
Inhibition of phosphatidylinositol 3-kinase delta (PI3Kdelta), a linchpin in the
pre-B-cell receptor and interleukin 7 receptor signaling pathways critical to B
cell development (with CAL-101 [idelalisib]), interrupts a double-negative
feedback loop, enhancing GC-regulated transcription to synergistically kill even
highly resistant B-ALL with diverse genetic backgrounds. This work not only
identifies numerous opportunities for enhanced lymphoid-specific combination
chemotherapies that have the potential to overcome treatment resistance, but is
also a valuable resource for understanding GC biology and the mechanistic details
of GR-regulated transcription.
PMID- 28424166
TI - Applying fluid biomarkers to Alzheimer's disease.
AB - Alzheimer's disease (AD) is a common neurodegenerative disease that starts with a
clinically silent phase of a decade or more during which brain pathologies
accumulate predominantly in the medial temporal lobe but also elsewhere in the
brain. Network dysfunction and clinical symptoms typically appear when senile
plaque (amyloid-beta) and neurofibrillary tangle (tau) pathologies meet in the
brain parenchyma, producing synapse and neuronal loss. For plaque and tangle
pathologies, reliable fluid biomarkers have been developed. These require
sampling of cerebrospinal fluid. Reliable blood tests for plaque and tangle
pathologies are currently lacking, but blood tests for general neurodegeneration
have recently been developed. In AD, plaques and tangles often coexist with other
pathologies, including Lewy bodies, and to what extent these contribute to
symptoms is currently unknown. There are also important differential diagnoses
that may be possible to distinguish from AD with the aid of biomarkers. The scope
of this review is fluid biomarkers for AD and related pathologies. The purpose is
to provide the reader with an updated account of currently available fluid
biomarkers for AD and clinically relevant differential diagnoses.
PMID- 28424168
TI - MiR-9-5p promotes MSC migration by activating beta-catenin signaling pathway.
AB - Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages,
but the very limited number of cells that migrate to the damaged region strongly
restricts their therapeutic applications. Full understanding of mechanisms
regulating MSC migration will help to improve their migration ability and
therapeutic effects. Increasing evidence shows that microRNAs play important
roles in the regulation of MSC migration. In the present study, we reported that
miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs
with high migration ability. Overexpression of miR-9-5p promoted MSC migration,
whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate
the underlying mechanism, we screened the target genes of miR-9-5p and report for
the first time that CK1alpha and GSK3beta, two inhibitors of beta-catenin
signaling pathway, were direct targets of miR-9-5p in MSCs and that
overexpression of miR-9-5p upregulated beta-catenin signaling pathway. In line
with these data, inhibition of beta-catenin signaling pathway by FH535 decreased
the miR-9-5p-promoted migration of MSCs, while activation of beta-catenin
signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR
9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as
well as the reorganization of F-actin were affected by the expression of miR-9
5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration
by upregulating beta-catenin signaling pathway, shedding light on the
optimization of MSCs for cell replacement therapy through manipulating the
expression level of miR-9-5p.
PMID- 28424169
TI - Identification of the fatty acid activation site on human ClC-2.
AB - Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl
channel activators. Molecular and cellular mechanisms underlying this activation
were examined. Role of a four-amino acid PKA activation site, RGET691, of hClC-2
was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2
expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP
concentration ([cAMP]i), EP2, or EP4 receptor agonist activity. All fatty acids
[lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and
elaidic acid] caused significant rightward shifts in concentration-dependent Cl-
current activation (increasing EC50s) with mutant compared with WT hClC-2
channels, without changing time and voltage dependence, current-voltage
rectification, or methadone inhibition of the channel. As with lubiprostone,
cobiprostone activation of hClC-2 occurred with PKA inhibitor (myristoylated
protein kinase inhibitor) present or when using double PKA activation site
(RRAA655/RGEA691) mutant. Cobiprostone did not activate human CFTR. Fatty acids
did not increase [cAMP]i in hClC-2/293EBNA or T84 cells. Using T84 CFTR knockdown
cells, cobiprostone increased hClC-2 Cl- currents without increasing [cAMP]i,
while PGE2 and forskolin-IBMX increased both. Fatty acids were not agonists of
EP2 or EP4 receptors. L-161,982, a supposed EP4-selective inhibitor, had no
effect on lubiprostone-activated hClC-2 Cl- currents but significantly decreased
T84 cell barrier function measured by transepithelial resistance and fluorescent
dextran transepithelial movement. The present findings show that RGET691 of hClC
2 (possible binding site) plays an important functional role in fatty acid
activation of hClC-2. PKA, [cAMP]i, and EP2 or EP4 receptors are not involved.
These studies provide the molecular basis for fatty acid regulation of hClC-2.
PMID- 28424170
TI - ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF
signaling and angiogenesis.
AB - Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria
play a critical role in growth factor-induced switch from a quiescent to an
angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible
ROS produced from different sources can coordinate to stimulate VEGF signaling
and drive the angiogenic process remains unknown. Using the cytosol- and
mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging,
here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP
oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min,
which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression
of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine
phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and
proliferation at the similar extent. Exogenous hydrogen peroxide (H2O2) or
overexpression of Nox4, which produces H2O2, increases mitochondrial ROS (mtROS),
which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H2O2
to promote mtROS production. Mechanistically, H2O2 increases S36 phosphorylation
of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by
siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation
defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC
migration, and proliferation. In summary, Nox4-derived H2O2 in part activates
Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and
angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS
induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which
drives sustained activation of angiogenesis signaling program.
PMID- 28424173
TI - Association between estimated glomerular filtration rate and outcomes in patients
with diabetic foot ulcers: a 3-year follow-up study.
AB - OBJECTIVE: End-stage renal disease and dialysis have been proven to be associated
with poor prognoses in diabetic foot ulcers (DFUs). However, it has rarely been
reported whether and to what extent milder renal insufficiency affects the
prognosis. The purpose of this study was to investigate the categorized impact of
estimated glomerular filtration (eGFR) on the outcomes of patients with DFU.
DESIGN AND METHODS: Three hundred and sixty-six DFU patients hospitalized in a
Chinese tertiary hospital were recruited and classified into 4 groups according
to the eGFRs as follows: normal (>=90), mildly reduced (60-89), moderately
reduced (30-59), and severely reduced (<30). These patients were followed-up for
an average of 37 months to observe the outcomes, including ulcer healing,
amputation, ulcer recurrence, cardiac or cerebrovascular events and death. The
associations between eGFR and the outcomes were analysed by Cox proportional
hazards models. RESULTS: Compared to patients with normal eGFR, patients with
moderately reduced eGFR had higher risk of healing failure (hazard ratio (HR) =
2.08, 95% confidence interval (CI): 1.13-3.82), cardiac events (HR = 5.25, 95%
CI: 2.17-12.89) and death (HR = 3.54, 95% CI: 1.36-9.20). Severely reduced eGFR
was associated with higher incidence of healing failure (HR = 2.84, 95% CI: 1.25
6.49) and death (HR = 4.45, 95% CI: 1.23-16.07). The impact of eGFR on ulcer
recurrence and cerebrovascular events was not observed in all groups.
CONCLUSIONS: Moderately and severely reduced eGFR in patients with DFU were
independent predictors for poor prognoses of both the limbs and the patients.
PMID- 28424174
TI - The clinical value of regular thyroid function tests during amiodarone treatment.
AB - OBJECTIVE: Amiodarone is used for the maintenance of sinus rhythm in patients
with arrhythmias, but thyroid dysfunction (amiodarone-induced thyrotoxicosis
(AIT) or amiodarone-induced hypothyroidism (AIH)) is a common adverse effect. As
the onset of AIT and AIH may be unpredictable, the value of long-term regular
monitoring of amiodarone treated patients for thyroid dysfunction is still
uncertain. DESIGN: We retrospectively documented the frequency at which overt
thyroid dysfunction was preceded by subclinical thyroid dysfunction. METHODS: We
included 303 patients treated with amiodarone between 1984 and 2007. AIT was
defined as a lowered TSH level with an elevated free thyroxine (FT4) and AIH was
defined as an elevated TSH level with a decreased or subnormal FT4. Subclinical
AIT was defined as a lowered TSH level with a normal FT4 and subclinical AIH as
an elevated TSH level with a normal FT4. RESULTS: 200 men and 103 women, aged 62
+/- 12.0 years, suffering from atrial (260) or ventricular (43) arrhythmias, were
evaluated. During a median follow-up of 2.8 (1.0-25) years, 44 patients developed
AIT and 33 AIH. In 42 (55%) patients who developed AIT/AIH, earlier thyroid
function tests showed no subclinical AIT or subclinical AIH. In 35 (45%)
patients, AIT/AIH was preceded by subclinical AIT or subclinical AIH (16/44 for
AIT and 19/33 for AIH). CONCLUSIONS: In a considerable proportion of patients who
developed AIT/AIH, earlier thyroid function tests showed no subclinical AIT/AIH.
Less than half of the patients with a subclinical event subsequently developed
overt AIT/AIH. This study provides data to reconsider the yield of regular
testing of thyroid function to predict overt thyroid dysfunction in amiodarone
treated patients.
PMID- 28424171
TI - European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition -
Chapter 2: Classification and terminologySupported by the EGS Foundation: Part 1:
Foreword; Introduction; Glossary; Chapter 2 Classification and Terminology.
PMID- 28424175
TI - Correction.
PMID- 28424176
TI - Archivist: Is appendicectomy really necessary?
PMID- 28424178
TI - Archivist: Joint injections and methotrexate in JIA: better together?
PMID- 28424177
TI - Developmental and behavioural associations of burns and scalds in children: a
prospective population-based study.
AB - OBJECTIVE: To investigate child developmental and behavioural characteristics and
risk of burns and scalds. DESIGN: Data on burns in children up to 11 years from
12 966 participants in the Avon Longitudinal Study of Parents and Children were
linked to developmental profiles measured before the burn injury. MEASURES:
Preinjury profiles of the children derived from maternal questionnaires completed
in pregnancy, and at 6, 18, 42, 47 and 54 months. Injury data collected by
questionnaire at 6, 15 and 24 months and 3.5, 4.5, 5.5, 6.5, 8.5 and 11 years of
age. RESULTS: Incidence: Burn rates were as follows: birth-2 years
71.9/1000/year; 2-4.5 years 42.2/1000/year; 5-11 years 14.3/1000/year. Boys <2
years were more likely to sustain burns, and girls had more burns between age 5
and 11 years. Medical attention was sought for 11% of burn injuries. Development:
Up to age 2 years, burns were more likely in children with the most advanced
gross motor developmental scores and the slowest fine motor development. Children
with coordination problems at 4.5 years of age had increased risk of burns
between 5 and 11 years. No associations were observed with cognitive skills.
Behaviour: At 3.5 years, the Strengths and Difficulties Questionnaire scores and
reported frequent temper tantrums predicted subsequent burns in primary school
age. After adjustment for confounders, burns in the preschool period were related
to gender and motor development, and in school-aged children, to frequent temper
tantrums, hyperactivity and coordination difficulties. CONCLUSION: Child factors
associated with increased risk of burns were male gender in infancy and female
gender at school age, advanced gross motor development, coordination
difficulties, hyperactivity and problems with emotional regulation.
PMID- 28424181
TI - Variability in the cardiometabolic effects of omega-3 long-chain PUFAs:
background diet, timing, and genetics.
PMID- 28424182
TI - Human milk oligosaccharides vary among populations.
PMID- 28424183
TI - Biomarker-calibrated nutrient intake and healthy diet index associations with
mortality risks among older and frail women from the Women's Health Initiative.
AB - Background: Although studies to date have confirmed the association between
nutrition and frailty, the impact of dietary intake and dietary patterns on
survivorship in those with frailty is yet to be examined in a well-powered cohort
with validated frailty status. Moreover, previous studies were limited by
measurement error from dietary self-reports.Objective: We derived biomarker
calibrated dietary energy and protein intakes to address dietary self-report
error. Using these data, we then evaluated the association of mortality in older
women with frailty and dietary intake and healthy diet indexes, such as the
alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension
(DASH) score, and the Dietary Inflammatory Index (DII).Design: The analytic
sample included 10,034 women aged 65-84 y with frailty and complete dietary data
from the Women's Health Initiative Observational Study. Frailty was assessed with
modified Fried's criteria. Dietary data were collected by food-frequency
questionnaire.Results: Over a mean follow-up period of 12.4 y, 3259 (31%) deaths
occurred. The HRs showed progressively decreased rates of mortality in women with
higher calibrated dietary energy intakes (P-trend = 0.003), higher calibrated
dietary protein intakes (P-trend = 0.03), higher aMED scores (P-trend = 0.006),
and higher DASH scores (P-trend = 0.02). Although the adjusted point estimates of
HRs (95% CIs) for frail women scoring in the second, third, and fourth quartiles
on DII measures were 1.15 (1.03, 1.27), 1.28 (1.15, 1.42), and 1.24 (1.12, 1.38),
respectively, compared with women in the first quartile, no overall effect was
observed across quartiles (P-trend = 0.35). Subgroup analyses by chronic
morbidity or smoking status or by excluding women with early death did not
substantially change these findings.Conclusions: The current study highlights the
importance of nutrition in older, frail women. Diet quality and quantity should
be considered in managing persons with frailty.
PMID- 28424184
TI - Demographic, lifestyle, and genetic determinants of circulating concentrations of
25-hydroxyvitamin D and vitamin D-binding protein in African American and
European American women.
AB - Background: Vitamin D may have anticancer activities. The high prevalence of
vitamin D deficiency in African Americans (AAs) may be a contributing factor to
the cancer health disparities between AAs and European Americans
(EAs).Objectives: We compared concentrations of 25(OH)D and vitamin D-binding
protein (VDBP) in AA and EA women and investigated determinants of the vitamin D
biomarker concentrations in both populations.Design: We used data and
biospecimens from 909 AA and 847 EA healthy control subjects from the Carolina
Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS) in the
African American Breast Cancer Epidemiology and Risk Consortium. We measured
plasma 25(OH)D and VDBP concentrations in all participants and genotyped 67
vitamin D-related genes in AA women only.Results: AA women had lower 25(OH)D
concentrations than did EA women (mean +/- SD: 14.2 +/- 8.1 compared with 21.1 +/
11.5 ng/mL, respectively; P < 0.0001) but similar concentrations of VDBP (mean
+/- SD: 344 +/- 133 compared with 336 +/- 124 MUg/mL, respectively; P = 0.25).
With VDBP and other factors controlled for, the observed racial difference in
25(OH)D concentrations did not diminish. Relations of demographic and lifestyle
factors with 25(OH)D were similar between AA and EA women. Although none of the
genetic variants that have been identified in previous genome-wide association
studies of 25(OH)D concentrations in EAs were significant (P > 0.05) in AAs, AA
women who carried the allele of a functional single nucleotide polymorphism
rs4988235, which has been previously associated with lactase expression and
lactose tolerance, had higher dietary vitamin D intake and higher measured
25(OH)D concentrations.Conclusions: AA women have lower concentrations of total
25(OH)D than EA women do, but both groups have similar VDBP concentrations,
suggesting that there are lower concentrations of free 25(OH)D in AAs. Although
demographic and lifestyle determinants of 25(OH)D concentrations are similar
between the 2 groups, genetic determinants may be ethnicity specific. Larger
studies in AAs will be needed to fully elucidate the underlying determinants of
low vitamin D concentrations in AA populations.
PMID- 28424185
TI - Very-long-chain omega-3 fatty acid supplements and adipose tissue functions: a
randomized controlled trial.
AB - Background: Increased omega-3 (n-3) fatty acid consumption is reported to benefit
patients with metabolic syndrome, possibly due to improved adipose tissue
function.Objective: We tested the effects of high-dose, very-long-chain omega-3
fatty acids on adipose tissue inflammation and insulin regulation of
lipolysis.Design: A double-blind, placebo-controlled study compared 6 mo of 3.9 g
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/d (4.2 g total omega
3/d; n = 12) with a placebo (4.2 g oleate/d; n = 9) in insulin-resistant adults.
Before and after treatment, the volunteers underwent adipose tissue biopsies to
measure the total (CD68+), pro- (CD14+ = M1), and anti- (CD206+ = M2)
inflammatory macrophages, crown-like structures, and senescent cells, as well as
a 2-step pancreatic clamping with a [U-13C]palmitate infusion to determine the
insulin concentration needed to suppress palmitate flux by 50%
(IC50(palmitate)f).Results: In the omega-3 group, the EPA and DHA contributions
to plasma free fatty acids increased (P = 0.0003 and P = 0.003, respectively), as
did the EPA and DHA content in adipose tissue (P < 0.0001 and P < 0.0001,
respectively). Despite increases in adipose and plasma EPA and DHA in the omega-3
group, there were no significant changes in the IC50(palmitate)f (19 +/- 2
compared with 24 +/- 3 MUIU/mL), adipose macrophages (total: 31 +/- 2/100
adipocytes compared with 33 +/- 2/100 adipocytes; CD14+: 13 +/- 2/100 adipocytes
compared with 14 +/- 2/100 adipocytes; CD206+: 28 +/- 2/100 adipocytes compared
with 29 +/- 3/100 adipocytes), crown-like structures (1 +/- 0/10 images compared
with 1 +/- 0/10 images), or senescent cells (4% +/- 1% compared with 4% +/- 1%).
There were no changes in these outcomes in the placebo group.Conclusions: Six
months of high-dose omega-3 supplementation raised plasma and adipose omega-3
fatty acid concentrations but had no beneficial effects on adipose tissue
lipolysis or inflammation in insulin-resistant adults. This trial was registered
at clinicaltrials.gov as NCT01686568.
PMID- 28424187
TI - A Mediterranean diet lowers blood pressure and improves endothelial function:
results from the MedLey randomized intervention trial.
AB - Background: The consumption of a Mediterranean diet (MedDiet) is associated with
a lower risk of cardiovascular disease. However, its impact on blood pressure and
endothelial function is not clear.Objective: We sought to determine the effects
of adhering to the consumption of a MedDiet for 6 mo on blood pressure and
endothelial function in older, healthy Australians.Design: A total of 166 men and
women aged >64 y were allocated via minimization to consume either a MedDiet (n =
85) or their habitual diet (HabDiet; control: n = 81) for 6 mo. The MedDiet
comprised mainly plant foods, abundant extra-virgin olive oil, and minimal red
meat and processed foods. A total of 152 participants commenced the study, and
137 subjects completed the study. Home blood pressure was measured on 5
consecutive days at baseline (n = 149) and at 3 and 6 mo. Endothelial function (n
= 82) was assessed by flow-meditated dilatation (FMD) at baseline and 6 mo.
Dietary intake was monitored with the use of 3-d weighed food records. Data were
analyzed with the use of linear mixed-effects models to determine adjusted
between-group differences.Results: The MedDiet adherence score increased
significantly in the MedDiet group but not in the HabDiet group (P < 0.001). The
MedDiet, compared with the HabDiet, resulted in lower systolic blood pressure (P
diet * time interaction = 0.02) [mean: -1.3 mm Hg (95% CI: -2.2, -0.3 mm Hg; P =
0.008) at 3 mo and -1.1 mm Hg (95% CI: -2.0, -0.1 mm Hg; P = 0.03) at 6 mo]. At 6
mo, the percentage of FMD was higher by 1.3% (95% CI: 0.2%, 2.4%; P = 0.026) in
the MedDiet group.Conclusion: Australian men and women who consumed a MedDiet for
6 mo had small but significantly lower systolic blood pressure and improved
endothelial function. This trial was registered at www.anzctr.org.au as
ACTRN12613000602729.
PMID- 28424186
TI - Circulating concentrations of biomarkers and metabolites related to vitamin
status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and
Australian populations.
AB - Background: Circulating concentrations of biomarkers that are related to vitamin
status vary by factors such as diet, fortification, and supplement use. Published
biomarker concentrations have also been influenced by the variation across
laboratories, which complicates a comparison of results from different
studies.Objective: We robustly and comprehensively assessed differences in
biomarkers that are related to vitamin status across geographic regions.Design:
The trial was a cross-sectional study in which we investigated 38 biomarkers that
are related to vitamin status and one-carbon and tryptophan metabolism in serum
and plasma from 5314 healthy control subjects representing 20 cohorts recruited
from the United States, Nordic countries, Asia, and Australia, participating in
the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized
laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'
phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and
alpha-tocopherol as well as combined vitamin scores that were based on these
nutrients showed that the general B-vitamin concentration was highest in the
United States and that the B vitamins and lipid soluble vitamins were low in
Asians. Conversely, circulating concentrations of metabolites that are inversely
related to B vitamins involved in the one-carbon and kynurenine pathways were
high in Asians. The high B-vitamin concentration in the United States appears to
be driven mainly by multivitamin-supplement users.Conclusions: The observed
differences likely reflect the variation in intake of vitamins and, in
particular, the widespread multivitamin-supplement use in the United States. The
results provide valuable information about the differences in biomarker
concentrations in populations across continents.
PMID- 28424188
TI - Nutritional profile of Supplemental Nutrition Assistance Program household food
and beverage purchases.
AB - Background: The Supplemental Nutrition Assistance Program (SNAP), which is the
largest federal nutrition assistance program in the United States, serves nearly
1 of 7 Americans. To date, few studies have examined food and beverage purchase
behaviors in SNAP participants with the use of electronic purchase
data.Objective: In this cross-sectional study, we examined household store
purchases of key food, beverage, and nutrient groups in SNAP participants and
nonparticipants.Design: Using a data set of US households' (n = 98,256 household
by-quarter observations) packaged food and beverage purchases and SNAP status
[current participant, income-eligible nonparticipant (income <=130% of the
Federal Poverty Level [FPL]), and higher-income nonparticipants (income >130% of
the FPL)] from 3 quarters during 2012-2013, we estimated pooled ordinary least
squares models, clustered at the household level, to examine the association
between SNAP status and purchases while controlling for sociodemographic
characteristics. We examined purchases of health- and policy-relevant food and
beverage groups [e.g., fruit and sugar-sweetened beverages (SSBs)] and nutrients
(e.g., total calories and sodium).Results: Regardless of SNAP status, households
had low mean purchases of fruit, vegetables, and fiber and high mean purchases of
junk foods, saturated fat, and sodium. After adjustment for multiple comparisons
and demographic characteristics, we found significant differences by SNAP status
of purchases of fruit, processed meat, salty snacks, sweeteners and toppings,
SSBs, and total calories, fiber, sugar, and sodium. Several of these differences
were clinically important. For example, compared with income-eligible and higher
income nonparticipants, SNAP participants purchased an additional ~15-20 kcal .
person-1 . d-1 from SSBs (P < 0.0001) and ~174-195 mg total Na . person-1 . d-1
(P <0.0001). Results were robust to corrections for sample-selection bias and to
the exclusion of observations with potentially misreported SNAP
status.Conclusions: American households, including SNAP households, show room for
improvement in the nutritional quality of store purchases. New interventions and
policies may be needed to improve food and beverage purchases in both SNAP and
non-SNAP households.
PMID- 28424189
TI - Diagnostic criteria for severe acute malnutrition among infants aged under 6 mo.
AB - Background: There is an increasing recognition of malnutrition among infants
under 6 mo of age (U6M). Current diagnosis criteria use weight-for-length z
scores (WLZs), but the 2006 WHO standards exclude infants shorter than 45 cm. In
older children, midupper arm circumference (MUAC) predicts mortality better than
does WLZ. Outcomes may also be influenced by exposure to HIV and size or
gestational age at birth. Diagnostic thresholds for WLZ, MUAC, and other indexes
have not been fully evaluated against mortality risk among U6M infants.Objective:
The aim was to determine the association of anthropometric indexes with risks of
inpatient and postdischarge mortality among U6M infants recruited at the time of
hospitalization.Design: We analyzed data from a cohort of U6M infants admitted to
Kilifi County Hospital (2007-2013), Kenya. The primary outcomes were inpatient
death and death during follow-up over 1 y after discharge. We calculated adjusted
RRs for inpatient mortality and HRs for postdischarge mortality for different
anthropometric measures and thresholds. Discriminatory value was assessed by
using receiver operating characteristic curves.Results: A total of 2882 infants
were admitted: 140 (4.9%) died in the hospital and 1405 infants were followed up
after discharge. Of these, 75 (5.3%) died within 1 y during 1318 child-years of
observation. MUAC and weight-for-age z score (WAZ) predicted inpatient and
postdischarge mortality better than did WLZ (P < 0.0001). A single MUAC threshold
of <11.0 cm performed similarly to MUAC thresholds that varied with age (all P >
0.05) and performed better than WLZ <-3 for both inpatient and postdischarge
mortality (both P < 0.001). Reported small size at birth did not reduce the risk
of death associated with anthropometric indexes.Conclusions: U6M infants at the
highest risk of death are best targeted by using MUAC or WAZ. Further research
into the effectiveness of potential interventions is required.
PMID- 28424191
TI - The D-lemma: narrow-band UV type B radiation versus vitamin D supplementation
versus sunlight for cardiovascular and immune health.
PMID- 28424190
TI - Odd-chain fatty acids as a biomarker for dietary fiber intake: a novel pathway
for endogenous production from propionate.
AB - Background: The risk of type 2 diabetes is inversely correlated with plasma
concentrations of odd-chain fatty acids [OCFAs; pentadecanoic acid (15:0) and
heptadecanoic acid (17:0)], which are considered as biomarkers for dairy fat
intake in humans. However, rodent studies suggest that OCFAs are synthesized
endogenously from gut-derived propionate. Propionate increases with dietary fiber
consumption and has been shown to improve insulin sensitivity.Objective: We
hypothesized that OCFAs are produced in humans from dietary fibers by a novel
endogenous pathway.Design: In a randomized, double-blind crossover study, 16
healthy individuals were supplemented with cellulose (30 g/d), inulin (30 g/d),
or propionate (6 g/d) for 7 d. In addition, human hepatoma cells were incubated
with different propionate concentrations. OCFAs were determined in plasma
phospholipids and hepatoma cells by gas chromatography.Results: Cellulose did not
affect plasma OCFA levels, whereas inulin and propionate increased pentadecanoic
acid by ~17% (P < 0.05) and 13% (P = 0.05), respectively. The effect on
heptadecanoic acid was even more pronounced, because it was elevated in almost
all participants by inulin (11%; P < 0.01) and propionate (13%; P < 0.001).
Furthermore, cell culture experiments showed a positive association between
propionate and OCFA levels (R2 = 0.99, P < 0.0001), whereas palmitate (16:0) was
negatively correlated (R2 = 0.83, P = 0.004).Conclusions: Our data show that gut
derived propionate is used for the hepatic synthesis of OCFAs in humans. The
association of OCFAs with a decreased risk of type 2 diabetes may therefore also
relate to dietary fiber intake and not only dairy fat. This trial was registered
at www.germanctr.de as DRKS00010121.
PMID- 28424192
TI - Sodium, sugar, and fat content of complementary infant and toddler foods sold in
the United States, 2015.
AB - Background: As part of a healthy diet, limiting intakes of excess sodium, added
sugars, saturated fat, and trans fat has been recommended. The American Heart
Association recommends that children aged <2 y should avoid added
sugars.Objective: We sought to determine commercial complementary infant-toddler
food categories that were of potential concern because of the sodium, added
sugar, saturated fat, or trans fat content.Design: Nutrition label information
(e.g., serving size, sodium, saturated fat, trans fat) for 1032 infant and
toddler foods was collected from manufacturers' websites and stores from May to
July 2015 for 24 brands, which accounted for >95% of infant-toddler food sales.
The presence of added sugars was determined from the ingredient list. Reference
amount customarily consumed (RACC) categories were used to group foods and
standardize serving sizes. A high sodium content was evaluated on the basis of
the Upper Intake Level for children aged 1-3 y and the number of potential
servings per day ([i.e., 1500 mg/7 servings (>210 mg/RACC)], a sodium amount >200
mg/100 g, or a mean sodium density >1000 mg/1000 kcal.Results: In 2015, most
commercial infant-only vegetables, fruit, dinners, and cereals were low in
sodium, contained no saturated fat, and did not contain added sugars. On average,
toddler meals contained 2233 mg Na/1000 kcal, and 84% of the meals had >210 mg
Na/RACC (170 g), whereas 69% of infant-toddler savory snacks had >200 mg Na/100
g. More than 70% of toddler meals, cereal bars and breakfast pastries, and infant
toddler grain- or dairy-based desserts contained >=1 sources of added sugar.
Approximately 70% of toddler meals contained saturated fat (mean: 1.9 g/RACC),
and no commercial infant-toddler foods contained trans fats.Conclusion: Most
commercial toddler meals, cereal bars and breakfast pastries, and infant-toddler
snacks and desserts have high sodium contents or contain added sugars, suggesting
a need for continued public health efforts to support parents in choosing
complementary foods for their infants and toddlers.
PMID- 28424193
TI - Study Suggests Treatment Approaches for Cholangiocarcinomas.
AB - A comprehensive genome profile of cholangiocarcinoma reveals that the tumors fall
into four molecular classes. The study suggests that patients with IDH1/2
mutations could benefit from drugs that inhibit oxidative phosphorylation or that
target mutations in chromatin remodeling genes. The work also shows that some
liver cancers are closely related to cholangiocarcinomas.
PMID- 28424194
TI - Common care practices among effective community-based specialist palliative care
teams: a qualitative study.
AB - OBJECTIVE: Evidence has shown that, despite wide variation in models of care,
community-based specialist palliative care teams can improve outcomes and reduce
acute care use at end of life. The goal of this study was to explore similarities
in care practices among effective and diverse specialist teams to inform the
development of other community-based teams. METHODS: Interviews with 78 providers
and administrators from 11 distinct community-based specialist palliative care
teams from Ontario, Canada were conducted. Interviews were audio-recorded,
transcribed and analysed using an inductive approach to identify common themes.
RESULTS: 3 key themes across all teams emerged. First, the distinct models of
care were generally summarised into 3 models: primary care and specialist
providers either collaborated by transferring, sharing or consulting in care.
Second, teams explicitly or implicitly followed 7 common care practices related
to: specialised expertise 24/7; intrateam communication; timeliness; physical
symptom and psychosocial-spiritual management; education; peace and fulfilment;
and advocacy for patient preferences. Third, all teams emphasised the importance
of team building, even more than using clinical tools and processes. CONCLUSIONS:
Despite wide variation in models of care among community-based specialist
palliative care teams, this large qualitative study identified several common
themes in care practices that can guide the development of other teams.
PMID- 28424195
TI - Thyroid skeletal metastasis: pain management with verteblation.
AB - The combination of percutaneous vertebroplasty with radiofrequency ablation
(verteblation) has not shown to be an effective measure of pain management in
patients with metastatic lesions of the spine. The use of this novel technique
has not been previously described in metastatic disease from thyroid cancer. We
would like to report our experience after treating a patient affected by a
thyroid carcinoma and an osteolytic spine metastasis. The patient suffered from
life-limiting pain and was successfully treated with a combination of
vertebroplasty and radiofrequency ablation. This case shows that the indications
of verteblation may be expanded in the palliative treatment of metastatic disease
from thyroid carcinoma.
PMID- 28424199
TI - Further research supports association between antidepressant use and elevated
risk of postpartum haemorrhage.
PMID- 28424198
TI - Pneumococcal Capsular Polysaccharide Immunity in the Elderly.
AB - Immunity to pneumococcal infections is impaired in older people, and current
vaccines are poorly protective against pneumococcal disease in this population.
Naturally acquired immunity to pneumococcal capsular polysaccharides develops
during childhood and is robust in young adults but deteriorates with advanced
age. In particular, antibody levels and function are reduced in older people.
Pneumococcal vaccines are recommended for people >65 years old. However, the
benefits of polysaccharide and protein-conjugated vaccines in this population are
small, because of both serotype replacement and incomplete protection against
vaccine serotype pneumococcal disease. In this review, we overview the immune
mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular
polysaccharide immunity declines with age, including altered colonization
dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired
mucosal immunity.
PMID- 28424200
TI - Whole-Exome Sequencing of Metaplastic Breast Carcinoma Indicates Monoclonality
with Associated Ductal Carcinoma Component.
AB - Purpose: Although most human cancers display a single histology, there are
unusual cases where two or more distinct tissue types present within a primary
tumor. One such example is metaplastic breast carcinoma, a rare but aggressive
cancer with a heterogeneous histology, including squamous, chondroid, and spindle
cells. Metaplastic carcinomas often contain an admixed conventional ductal
invasive or in situ mammary carcinoma component, and are typically triple
negative for estrogen receptor, progesterone receptor, and HER-2
amplification/overexpression. An unanswered question is the origin of metaplastic
breast cancers. While they may arise independently from their ductal components,
their close juxtaposition favors a model that postulates a shared origin, either
as two derivatives from the same primary cancer or one histology as an outgrowth
of the other. Understanding the mechanism of development of these tumors may
inform clinical decisions.Experimental Design: We performed exome sequencing for
paired metaplastic and adjacent conventional invasive ductal carcinomas in 8
patients and created a pipeline to identify somatic variants and predict their
functional impact, without having normal tissue. We then determined the genetic
relationships between the histologically distinct compartments.Results: In each
case, the tumor components have nearly identical landscapes of somatic mutation,
implying that the differing histologies do not derive from genetic clonal
divergence.Conclusions: A shared origin for tumors with differing histologies
suggests that epigenetic or noncoding changes may mediate the metaplastic
phenotype and that alternative therapeutic approaches, including epigenetic
therapies, may be required for metaplastic breast cancers. Clin Cancer Res;
23(16); 4875-84. (c)2017 AACR.
PMID- 28424201
TI - PIK3CA Mutations Contribute to Acquired Cetuximab Resistance in Patients with
Metastatic Colorectal Cancer.
AB - Purpose: Mutations in KRAS are considered to be the main drivers of acquired
resistance to epidermal growth factor receptor (EGFR) blockade in patients with
metastatic colorectal cancer (mCRC). However, the potential role of other genes
downstream of the EGFR signaling pathway in conferring acquired resistance has
not been extensively investigated.Experimental Design: Using circulating tumor
DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we
developed a targeted amplicon ultra-deep sequencing method to screen for low
abundance somatic mutations in a panel of genes that encode components of the
EGFR signaling pathway. Mutations with significantly increased variant
frequencies upon disease progression were selected by using quartile analysis.
The functional consequences of the identified mutations were validated in
cultured cells.Results: We analyzed 32 patients with acquired cetuximab
resistance in a development cohort. Of them, seven (22%) carried five novel
PIK3CA mutations, whereas eight (25%) carried previously reported KRAS mutations.
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N,
p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of
cetuximab. Only one novel PIK3CA mutation (p.K944N) was verified in one of the 27
patients with acquired resistance in a validation cohort, simultaneous KRAS and
PIK3CA hotspot mutations were detected in two patients. Among the above 59
acquired resistance patients, those with PIK3CA or RAS mutations detected in
ctDNA showed a pronounced decrease in progression-free survival than patients
with no mutation.Conclusions: The PIK3CA mutations may potentially contribute to
acquired cetuximab resistance in patients with mCRC. Clin Cancer Res; 23(16);
4602-16. (c)2017 AACR.
PMID- 28424203
TI - Relationships between the timing of budburst, plant traits, and distribution of
24 coexisting woody species in a warm-temperate forest in Japan.
AB - PREMISE OF THE STUDY: Timing of budburst (DBB) may be related to the functional
traits and distributions of woody species in temperate regions. Although many
previous studies have investigated DBB in a number of temperate species, it has
seldom been linked to multiple plant trait relationships. METHODS: DBB and plant
traits were investigated for 24 woody species for 2 years in a warm-temperate
secondary forest in Japan. Particular attention was paid to differences in trait
relationships between coexisting deciduous and evergreen broad-leaved species.
KEY RESULTS: DBB was correlated with plant traits in deciduous but not evergreen
broad-leaved species; DBB was later for deciduous species with greater leaf mass,
leaf area, vessel diameter, and leaf nitrogen content per unit mass. In addition,
DBB was later for species with more northern distributions in deciduous and
evergreen species. CONCLUSIONS: Clear differences in the trait relationships
between deciduous and evergreen broad-leaved species might be caused by different
selection pressures on DBB; selection is expected to be more severe in deciduous
species. Overall, the continuous variable of vessel diameter might be used as a
simple and effective trait to predict DBB of deciduous species regardless of wood
anatomy; however, no such traits were detected as effective predictors of DBB in
evergreen species at this study site. In addition, DBB was earlier for the
species of more southern distributions, suggesting that such species benefit more
from warming.
PMID- 28424202
TI - Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic
Cysts.
AB - Purpose: Pancreatic cysts are estimated to be present in 2%-3% of the adult
population. Unfortunately, current diagnostics do not accurately distinguish
benign cysts from those that can progress into invasive cancer. Misregulated
pericellular proteolysis is a hallmark of malignancy, and therefore, we used a
global approach to discover protease activities that differentiate benign
nonmucinous cysts from premalignant mucinous cysts.Experimental Design: We
employed an unbiased and global protease profiling approach to discover protease
activities in 23 cyst fluid samples. The distinguishing activities of select
proteases was confirmed in 110 samples using specific fluorogenic substrates and
required less than 5 MUL of cyst fluid.Results: We determined that the activities
of the aspartyl proteases gastricsin and cathepsin E are highly increased in
fluid from mucinous cysts. IHC analysis revealed that gastricsin expression was
associated with regions of low-grade dysplasia, whereas cathepsin E expression
was independent of dysplasia grade. Gastricsin activity differentiated mucinous
from nonmucinous cysts with a specificity of 100% and a sensitivity of 93%,
whereas cathepsin E activity was 92% specific and 70% sensitive. Gastricsin
significantly outperformed the most widely used molecular biomarker,
carcinoembryonic antigen (CEA), which demonstrated 94% specificity and 65%
sensitivity. Combined analysis of gastricsin and CEA resulted in a near perfect
classifier with 100% specificity and 98% sensitivity.Conclusions: Quantitation of
gastricsin and cathepsin E activities accurately distinguished mucinous from
nonmucinous pancreatic cysts and has the potential to replace current diagnostics
for analysis of these highly prevalent lesions. Clin Cancer Res; 23(16); 4865-74.
(c)2017 AACR.
PMID- 28424204
TI - A species on a tightrope: Establishment limitations of an endangered lichen in a
fragmented Mediterranean landscape.
AB - PREMISE OF THE STUDY: Habitat loss and forest fragmentation affect the dispersal
and establishment of species. Furthermore, populations growing far from the
species' optimal climate might be less viable because good-quality habitat can be
scarce and easily altered by smaller changes. The lichen Pectenia plumbea has
oceanic climatic requirements, so in the Mediterranean region it needs the
humidity provided by well-preserved forests to thrive, but most of this habitat
has disappeared and the remnants are fragmented. In central Spain, this species
occupies only a small proportion of the existing forests, so we aimed to
determine whether this scattered distribution is due to limitations on dispersal
or establishment. METHODS: We selected a Mediterranean fragmented forest surface
in central Spain and extracted environmental variables from 371 plots. We modeled
the presence and abundance of P. plumbea and developed species distribution
models (SDMs) to detect all the suitable habitats inside the Cabaneros National
Park area. KEY RESULTS: Pectenia plumbea was present in most of the habitats
predicted as good-quality and was generally absent from the poor-quality zones
(85.9% overall success). The abundance correlated fairly well with that predicted
by the SDM (67%). Both models show that P. plumbea is linked to high temperature
and precipitation. CONCLUSIONS: Good-quality habitat requirements for P. plumbea
that are similar to oceanic conditions are found only in specific forested, stony
slopes derived from historical land management. This habitat is scarce, but P.
plumbea has successfully tracked all of these scattered areas via its high
dispersal capacity.
PMID- 28424205
TI - The use of soil pollen to determine the sex of overhead individuals of a
temperate dioecious shrub.
AB - PREMISE OF THE STUDY: In dioecious species, determining the sex of individual
plants from one-time phenological observations is rarely feasible when some
individuals capable of reproducing are not flowering or fruiting at the time of
observation. Currently, sexing those individuals requires long-term phenological
data on individuals and populations, but such data are rarely available or
feasible to collect. We tested the hypothesis that differences in soil pollen
concentrations beneath the crowns of female and male plants would exist and be
sufficient to reliably determine the sex of the individual plant overhead in a
dioecious species. We predicted that soil pollen concentrations beneath male
plants would be significantly higher than beneath female plants because only
males produce pollen and pollen should accumulate in the soil underneath the male
plants over repeated flowering events. METHODS: We collected samples from surface
soil under both sexes of the insect-pollinated dioecious shrub, Aucuba japonica
(Garryaceae). KEY RESULTS: Pollen grains were present in surface soil in both Oe
and A horizons, and mean pollen concentration under males was significantly
higher than under females. Pollen concentrations beneath males were positively
correlated with male plant height, potentially reflecting greater pollen
production by larger individuals. CONCLUSIONS: Considering the small plant size
and relatively low pollen production of A. japonica, this method may hold promise
for sexing other dioecious species in the absence of direct phenological data.
Our phenology-free and relatively low-cost method for sexing dioecious plants may
be especially useful in tropical forests where many species are dioecious.
PMID- 28424206
TI - Extending the fossil record of Polytrichaceae: Early Cretaceous Meantoinea
alophosioides gen. et sp. nov., permineralized gametophytes with gemma cups from
Vancouver Island.
AB - PREMISE OF THE STUDY: Diverse in modern ecosystems, mosses are dramatically
underrepresented in the fossil record. Furthermore, most pre-Cenozoic mosses are
known only from compression fossils, lacking detailed anatomical information.
When preserved, anatomy vastly improves resolution in the systematic placement of
fossils. Lower Cretaceous deposits at Apple Bay (Vancouver Island, British
Columbia, Canada) contain a diverse anatomically preserved flora that includes
numerous bryophytes, many of which have yet to be characterized. Among them is a
polytrichaceous moss that is described here. METHODS: Fossil moss gametophytes
preserved in four carbonate concretions were studied in serial sections prepared
using the cellulose acetate peel technique. KEY RESULTS: We describe Meantoinea
alophosioides gen. et sp. nov., a polytrichaceous moss with terminal gemma cups
containing stalked, lenticular gemmae. Leaves with characteristic costal anatomy,
differentiated into sheathing base and free lamina and bearing photosynthetic
lamellae, along with a conducting strand in the stem, place Meantoinea in family
Polytrichaceae. The bistratose leaf lamina with an adaxial layer of mamillose
cells, short photosynthetic lamellae restricted to the costa, and presence of
gemma cups indicate affinities with basal members of the Polytrichaceae, such as
Lyellia, Bartramiopsis, and Alophosia. CONCLUSIONS: Meantoinea alophosioides
enriches the documented moss diversity of an already-diverse Early Cretaceous
plant fossil assemblage. This is the third moss described from the Apple Bay
plant fossil assemblage and represents the first occurrence of gemma cups in a
fossil moss. It is also the oldest unequivocal record of Polytrichaceae,
providing a hard minimum age for the group of 136 million years.
PMID- 28424207
TI - A distributed solute model: an extended two-pore model with application to the
glomerular sieving of Ficoll.
AB - One of the many unresolved questions regarding the permeability of the glomerular
filtration barrier is the reason behind the marked difference in permeability
between albumin and polysaccharide probe molecules such as Ficoll and dextran of
the same molecular size. Although the differences in permeability have been
mainly attributed to charge effects, we have previously shown that this would
require a highly charged filtration barrier, having a charge density that is ~10
times more than that on the albumin molecule. In this article, the classic two
pore model was extended by introducing size distributions on the solute
molecules, making them conformationally flexible. Experimental sieving data for
Ficoll from the rat glomerulus and from precision-made silicon nanopore membranes
were analyzed using the model. For the rat glomerulus a small-pore radius of 36.2
A and a geometric standard deviation (gSD) for the Ficoll size-distribution of
1.16 were obtained. For the nanopore membranes, a gSD of 1.24 and a small-pore
radius of 43 A were found. Interestingly, a variation of only ~16% in the size of
the polysaccharide molecule is sufficient to explain the difference in
permeability between albumin and Ficoll. Also, in line with previous data, the
effects of applying a size distribution on the solute molecule are only evident
when the molecular size is close to the pore size. Surely there is at least some
variation in the pore radii, and, likely, the gSD obtained in the current study
is an overestimation of the "true" variation in the size of the Ficoll molecule.
PMID- 28424208
TI - Architecture of the rat nephron-arterial network: analysis with micro-computed
tomography.
AB - Among solid organs, the kidney's vascular network stands out, because each
nephron has two distinct capillary structures in series and because
tubuloglomerular feedback, one of the mechanisms responsible for blood flow
autoregulation, is specific to renal tubules. Tubuloglomerular feedback and the
myogenic mechanism, acting jointly, autoregulate single-nephron blood flow. Each
generates a self-sustained periodic oscillation and an oscillating electrical
signal that propagates upstream along arterioles. Similar electrical signals from
other nephrons interact, allowing nephron synchronization. Experimental
measurements show synchronization over fields of a few nephrons; simulations
based on a simplified network structure that could obscure complex interactions
predict more widespread synchronization. To permit more realistic simulations, we
made a cast of blood vessels in a rat kidney, performed micro-computed tomography
at 2.5-MUm resolution, and recorded three-dimensional coordinates of arteries,
afferent arterioles, and glomeruli. Nonterminal branches of arcuate arteries form
treelike structures requiring two to six bifurcations to reach terminal branches
at the tree tops. Terminal arterial structures were either paired branches at the
tops of the arterial trees, from which 52.6% of all afferent arterioles
originated, or unpaired arteries not at the tree tops, yielding the other 22.9%;
the other 24.5% originated directly from nonterminal arteries. Afferent
arterioles near the corticomedullary boundary were longer than those farther
away, suggesting that juxtamedullary nephrons have longer afferent arterioles.
The distance separating origins of pairs of afferent arterioles varied randomly.
The results suggest an irregular-network tree structure with vascular nodes,
where arteriolar activity and local blood pressure interact.
PMID- 28424209
TI - The sulfilimine cross-link of collagen IV contributes to kidney tubular basement
membrane stiffness.
AB - Basement membranes (BMs), a specialized form of extracellular matrix, underlie
nearly all cell layers and provide structural support for tissues and interact
with cell surface receptors to determine cell behavior. Both macromolecular
composition and stiffness of the BM influence cell-BM interactions. Collagen IV
is a major constituent of the BM that forms an extensively cross-linked
oligomeric network. Its deficiency leads to BM mechanical instability, as
observed with glomerular BM in Alport syndrome. These findings have led to the
hypothesis that collagen IV and its cross-links determine BM stiffness. A
sulfilimine bond (S = N) between a methionine sulfur and a lysine nitrogen cross
links collagen IV and is formed by the matrix enzyme peroxidasin. In peroxidasin
knockout mice with reduced collagen IV sulfilimine cross-links, we find a
reduction in renal tubular BM stiffness. Thus this work provides the first direct
experimental evidence that collagen IV sulfilimine cross-links contribute to BM
mechanical properties and provides a foundation for future work on the
relationship of BM mechanics to cell function in renal disease.
PMID- 28424210
TI - UCP2 attenuates apoptosis of tubular epithelial cells in renal ischemia
reperfusion injury.
AB - Uncoupling protein-2 (UCP2) plays critical roles in energy metabolism and cell
survival. Previous investigations showed that UCP2 regulated the production of
extracellular matrix and renal fibrosis. However, little is known about UCP2 in
acute kidney injury (AKI). Here, we used Ucp2 knockout mice to investigate the
role of UCP2 in an AKI model generated by renal ischemia-reperfusion (I/R)
injury. The Ucp2 global knockout mice were born and grew normally without kidney
histological abnormality or renal dysfunction. Compared with littermates,
deletion of Ucp2 exacerbated I/R-induced AKI whereas increase of UCP2 by
conjugated linoleic acid (CLA) attenuated I/R injury. Tubular cell apoptosis and
autophagy were induced by I/R. After injury, more tubular cell apoptosis and less
autophagy were identified in the kidneys of knockout mice compared with their
littermates, and less apoptosis and more autophagy were observed in mice fed with
CLA. In vitro rotenone, an inhibitor of electron transport chain complex I, was
applied to induce energy depletion in cultured tubular epithelial cells. As
expected, rotenone-recovery (R/R) treatment induced tubular cell apoptosis and
autophagy. UCP2 plasmid transfection reduced cell apoptosis and facilitated
autophagy after R/R treatment, whereas UCP2 small interfering RNA (siRNA)
transfection sensitized cell apoptosis but reduced autophagy induced by R/R
treatment. Interference of autophagy by treatment with autophagy inhibitor 3
methyladenine or autophagy initiation protein Beclin-1 siRNA transfection
resulted in tubular cell apoptosis. Thus UCP2 attenuates I/R-induced AKI,
probably by reducing cell apoptosis through protection of autophagy.
PMID- 28424211
TI - Connecting tubule glomerular feedback mediates tubuloglomerular feedback
resetting after unilateral nephrectomy.
AB - Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure
(PGC) that can cause significant glomerular injury in the remnant kidney. PGC is
controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance.
Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1)
tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to
increased NaCl in the macula densa; and 2) connecting tubule glomerular feedback
(CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport
in the connecting tubule via the epithelial sodium channel (ENaC). Resetting of
TGF post-UNx can allow systemic pressure to be transmitted to the glomerulus and
cause renal damage, but the mechanism behind this resetting is unclear. Since
CTGF is an Af-Art dilatory mechanism, we hypothesized that CTGF is increased
after UNx and contributes to TGF resetting. To test this hypothesis, we performed
UNx in Sprague-Dawley (8) rats. Twenty-four hours after surgery, we performed
micropuncture of individual nephrons and measured stop-flow pressure (PSF). PSF
is an indirect measurement of PGC. Maximal TGF response at 40 nl/min was 8.9 +/-
1.24 mmHg in sham-UNx rats and 1.39 +/- 1.02 mmHg in UNx rats, indicating TGF
resetting after UNx. When CTGF was inhibited with the ENaC blocker benzamil (1
MUM/l), the TGF response was 12.29 +/- 2.01 mmHg in UNx rats and 13.03 +/- 1.25
mmHg in sham-UNx rats, indicating restoration of the TGF responses in UNx. We
conclude that enhanced CTGF contributes to TGF resetting after UNx.
PMID- 28424213
TI - Magnesium improves cisplatin-mediated tumor killing while protecting against
cisplatin-induced nephrotoxicity.
AB - Approximately 30% of all cancer patients treated with cisplatin, a widely used
broad-spectrum chemotherapeutic agent, experience acute kidney injury (AKI).
Almost all patients receiving cisplatin have magnesium (Mg) losses, which are
proposed to aggravate AKI. Currently, there are no methods to successfully treat
or prevent cisplatin-AKI. Whereas Mg supplementation has been shown to reduce AKI
in experimental models and several small clinical trials, the effects of Mg
status on tumor outcomes in immunocompetent tumor-bearing mice and humans have
not been investigated. The purpose of this study was to further examine the
effects of Mg deficiency (+/-Mg supplementation) on cisplatin-mediated AKI and
tumor killing in immunocompetent mice bearing CT26 colon tumors. Using a model
where cisplatin alone (20 mg/kg cumulative dose) produced minimal kidney injury,
Mg deficiency significantly worsened cisplatin-mediated AKI, as determined by
biochemical markers (blood urea nitrogen and plasma creatinine) and histological
renal changes, as well as markers of renal oxidative stress, inflammation, and
apoptosis. By contrast, Mg supplementation blocked cisplatin-induced kidney
injury. Using LLC-PK1 renal epithelial cells, we observed that Mg deficiency or
inhibition of Mg uptake significantly enhanced cisplatin-induced cytotoxicity,
whereas Mg supplementation protected against cytotoxicity. However, neither Mg
deficiency nor inhibition of Mg uptake impaired cisplatin-mediated killing of
CT26 tumor cells in vitro. Mg deficiency was associated with significantly larger
CT26 tumors in BALB/c mice when compared with normal-fed control mice, and Mg
deficiency significantly reduced cisplatin-mediated tumor killing in vivo.
Finally, Mg supplementation did not compromise cisplatin's anti-tumor efficacy in
vivo.
PMID- 28424212
TI - PDGF receptor-beta uses Akt/mTORC1 signaling node to promote high glucose-induced
renal proximal tubular cell collagen I (alpha2) expression.
AB - Increased expression of PDGF receptor-beta (PDGFRbeta) has been shown in renal
proximal tubules in mice with diabetes. The core molecular network used by high
glucose to induce proximal tubular epithelial cell collagen I (alpha2) expression
is poorly understood. We hypothesized that activation of PDGFRbeta by high
glucose increases collagen I (alpha2) production via the Akt/mTORC1 signaling
pathway in proximal tubular epithelial cells. Using biochemical and molecular
biological techniques, we investigated this hypothesis. We show that high glucose
increases activating phosphorylation of the PDGFRbeta, resulting in
phosphorylation of phosphatidylinositol 3-kinase. A specific inhibitor, JNJ
10198409, and small interfering RNAs targeting PDGFRbeta blocked this
phosphorylation without having any effect on MEK/Erk1/2 activation. We also found
that PDGFRbeta regulates high glucose-induced Akt activation, its targets tuberin
and PRAS40 phosphorylation, and finally, mTORC1 activation. Furthermore,
inhibition of PDGFRbeta suppressed high glucose-induced expression of collagen I
(alpha2) in proximal tubular cells. Importantly, expression of constitutively
active Akt or mTORC1 reversed these processes. As a mechanism, we found that JNJ
and PDGFRbeta knockdown inhibited high glucose-stimulated Hif1alpha expression.
Furthermore, overexpression of Hif1alpha restored expression of collagen I
(alpha2) that was inhibited by PDGFRbeta knockdown in high glucose-stimulated
cells. Finally, we show increased phosphorylation of PDGFRbeta and its
association with Akt/mTORC1 activation, Hif1alpha expression, and elevated
collagen I (alpha2) levels in the renal cortex of mice with diabetes. Our results
identify PDGFRbeta as a driver in activating Akt/mTORC1 nexus for high glucose
mediated expression of collagen I (alpha2) in proximal tubular epithelial cells,
which contributes to tubulointerstitial fibrosis in diabetic nephropathy.
PMID- 28424215
TI - Medical Marijuana Laws May Be Associated With A Decline In The Number Of
Prescriptions For Medicaid Enrollees.
AB - In the past twenty years, twenty-eight states and the District of Columbia have
passed some form of medical marijuana law. Using quarterly data on all fee-for
service Medicaid prescriptions in the period 2007-14, we tested the association
between those laws and the average number of prescriptions filled by Medicaid
beneficiaries. We found that the use of prescription drugs in fee-for-service
Medicaid was lower in states with medical marijuana laws than in states without
such laws in five of the nine broad clinical areas we studied. If all states had
had a medical marijuana law in 2014, we estimated that total savings for fee-for
service Medicaid could have been $1.01 billion. These results are similar to
those in a previous study we conducted, regarding the effects of medical
marijuana laws on the number of prescriptions within the Medicare population.
Together, the studies suggest that in states with such laws, Medicaid and
Medicare beneficiaries will fill fewer prescriptions.
PMID- 28424214
TI - Functional Conservation and Divergence among Homoeologs of TaSPL20 and TaSPL21,
Two SBP-Box Genes Governing Yield-Related Traits in Hexaploid Wheat.
AB - Maintaining high and stable yields has become an increasing challenge in wheat
breeding due to climate change. Although Squamosa-promoter binding protein (SBP)
box genes have important roles in plant development, very little is known about
the actual biological functions of wheat SBP-box family members. Here, we dissect
the functional conservation, divergence, and exploitation of homoeologs of two
paralogous TaSPL wheat loci during domestication and breeding. TaSPL20 and
TaSPL21 were highly expressed in the lemma and palea. Ectopic expressions of
TaSPL20/21 in rice exhibited similar functions in terms of promoting panicle
branching but had different functions during seed development. We characterized
all six TaSPL20/21 genes located across the three homoeologous (A, B, and D)
genomes. According to the functional analysis of naturally occurring variants in
20 environments, four favorable haplotypes were identified. Together, they
reduced plant height by up to 27.5%, and TaSPL21-6D-HapII increased 1000-grain
weight by 9.73%. Our study suggests that TaSPL20 and TaSPL21 homoeologs underwent
diversification in function with each evolving its own distinctive
characteristics. During domestication and breeding of wheat in China, favorable
haplotypes of each set were selected and exploited to varying degrees due to
their large effects on plant height and 1000-grain weight.
PMID- 28424216
TI - White coat.
PMID- 28424217
TI - Use of life jackets and other types of flotation for in-water recreation in
designated swim areas in Washington State.
AB - : Most fatal drownings worldwide occur in open water. Flotation devices may
protect swimmers. Their use by those recreating in water has not been described.
METHODS: Observational survey of swimmers and waders at designated swim sites at
lakes and rivers evaluated them by age group, sex, type of flotation used (life
jacket vs substandard flotation, eg, water wings, noodles, inflatables) and, for
children <6 years, being within arm's reach of an adult. RESULTS: Of 1967
swimmers/waders observed, 37% used some type of flotation device. Use rates,
especially of life jackets, decreased with increasing age. Children <6 years had
the highest use of some type of flotation (140/212, 66%) and the highest use of
life jackets (50.5%). Children <13 years were more likely to use flotation
devices and life jackets than teens (RR 6.78, 3.62 to 12.71); boys were more
likely than girls to wear life jackets (RR 1.47, 1.18 to 1.83). While teenagers
and adults used flotation (29.5% and 23.5%), they rarely used life jackets (2
3%). Boys <6 years who were further than arm's length of an adult were more
likely to wear life jackets than girls. Substandard flotation use did not differ
among age groups (15.5-26.5%) but their use was greater among females in most age
groups. CONCLUSIONS: Flotation devices were frequently used for recreational
wading and swimming in open water by all age groups. Life jacket use was limited
to children. Promoting use of flotation devices with safety standards that
provide protection as well as fun could potentially decrease open water drowning
rates.
PMID- 28424218
TI - GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in
C. elegans.
AB - Apoptotic cells generated by programmed cell death are engulfed by phagocytes and
enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes
involves a series of membrane-remodeling events that are governed by the
sequential actions of Rab GTPases and lead to formation of phagolysosomes, where
cell corpses are degraded. Here we identified gop-1 as a novel regulator of
apoptotic cell clearance in Caenorhabditis elegans Loss of gop-1 affects
phagosome maturation through the RAB-5-positive stage, causing defects in
phagosome acidification and phagolysosome formation, phenotypes identical to and
unaffected by loss of unc-108, the C. elegans Rab2 GOP-1 transiently associates
with cell corpse-containing phagosomes, and loss of its function abrogates
phagosomal association of UNC-108. GOP-1 interacts with GDP-bound and nucleotide
free UNC-108/Rab2, disrupts GDI-UNC-108 complexes, and promotes activation and
membrane recruitment of UNC-108/Rab2 in vitro. Loss of gop-1 also abolishes
association of UNC-108 with endosomes, causing defects in endosome and dense core
vesicle maturation. Thus, GOP-1 is an activator of UNC-108/Rab2 in multiple
processes.
PMID- 28424219
TI - Downregulation of RBO-PI4KIIIalpha Facilitates Abeta42 Secretion and Ameliorates
Neural Deficits in Abeta42-Expressing Drosophila.
AB - Phosphoinositides and their metabolizing enzymes are involved in Abeta42
metabolism and Alzheimer's disease pathogenesis. In yeast and mammals, Eighty
five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO),
forms a plasma membrane-localized protein complex with phosphatidylinositol-4
kinase Type IIIalpha (PI4KIIIalpha) and a scaffold protein to tightly control the
level of plasmalemmal phosphatidylinositol-4-phosphate (PI4P). Here, we report
that RBO binds to Drosophila PI4KIIIalpha, and that in an Abeta42-expressing
Drosophila model, separate genetic reduction of PI4KIIIalpha and RBO, or
pharmacological inhibition of PI4KIIIalpha ameliorated synaptic transmission
deficit, climbing ability decline, premature death, and reduced neuronal
accumulation of Abeta42 Moreover, we found that RBO-PI4KIIIa downregulation
increased neuronal Abeta42 release and that PI4P facilitated the assembly or
oligomerization of Abeta42 in/on liposomes. These results indicate that RBO
PI4KIIIa downregulation facilitates neuronal Abeta42 release and consequently
reduces neuronal Abeta42 accumulation likely via decreasing Abeta42 assembly
in/on plasma membrane. This study suggests the RBO-PI4KIIIalpha complex as a
potential therapeutic target and PI4KIIIalpha inhibitors as drug candidates for
Alzheimer's disease treatment.SIGNIFICANCE STATEMENT Phosphoinositides and their
metabolizing enzymes are involved in Abeta42 metabolism and Alzheimer's disease
pathogenesis. Here, in an Abeta42-expressing Drosophila model, we discovered and
studied the beneficial role of downregulating RBO or its interacting protein
PI4KIIIalpha-a protein that tightly controls the plasmalemmal level of PI4P
against the defects caused by Abeta42 expression. Mechanistically, RBO
PI4KIIIalpha downregulation reduced neuronal Abeta42 accumulation, and
interestingly increased neuronal Abeta42 release. This study suggests the RBO
PI4KIIIalpha complex as a novel therapeutic target, and PI4KIIIalpha inhibitors
as new drug candidates.
PMID- 28424220
TI - GABABR-Induced EGFR Transactivation Promotes Migration of Human Prostate Cancer
Cells.
AB - G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in
concert to regulate cell growth, proliferation, survival, and migration.
Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory
neurotransmitter GABA in the central nervous system. Increased expression of
GABABR has been detected in human cancer tissues and cancer cell lines, but the
role of GABABR in these cells is controversial and the underlying mechanism
remains poorly understood. Here, we investigated whether GABABR hijacks RTK
signaling to modulate the fates of human prostate cancer cells. RTK array
analysis revealed that the GABABR-specific agonist baclofen selectively induced
the transactivation of EGFR in PC-3 cells. EGFR transactivation resulted in the
activation of ERK1/2 by a mechanism that is dependent on Gi/o protein and that
requires matrix metalloproteinase-mediated proligand shedding. Positive
allosteric modulators (PAMs) of GABABR, such as CGP7930, rac-BHFF, and GS39783,
can function as PAM agonists to induce EGFR transactivation and subsequent ERK1/2
activation. Moreover, both baclofen and CGP7930 promoted cell migration and
invasion through EGFR signaling. In summary, our observations demonstrated that
GABABR transactivated EGFR in a ligand-dependent mechanism to promote prostate
cancer cell migration and invasion, thus providing new insights into developing a
novel strategy for prostate cancer treatment by targeting neurotransmitter
signaling.
PMID- 28424221
TI - Association Between Fetal Congenital Heart Defects and Maternal Risk of
Hypertensive Disorders of Pregnancy in the Same Pregnancy and Across Pregnancies.
AB - BACKGROUND: Both pregnant women carrying fetuses with heart defects and women
with hypertensive disorders of pregnancy often exhibit angiogenic imbalances,
suggesting that the same mechanisms are involved in the pathogenesis of the
former and the pathophysiology of the latter. We conducted a register-based
cohort study to determine whether offspring congenital heart defects are
associated with an increased risk of hypertensive disorders of pregnancy and
whether the mechanisms driving any association are primarily maternal or fetal.
METHODS: Among singleton pregnancies without chromosomal abnormalities lasting
>=20 weeks in Denmark from 1978 to 2011 (n= 1 972 857), we identified pregnancies
complicated by offspring congenital heart defects or early preterm preeclampsia,
late preterm preeclampsia, term preeclampsia, and gestational hypertension. We
used polytomous logistic regression to estimate odds ratios (ORs) for
associations between offspring congenital heart defects and maternal hypertensive
disorders of pregnancy overall and for specific heart defects. RESULTS: Offspring
congenital heart defects were strongly associated with early preterm preeclampsia
(OR, 7.00; 95% confidence interval [CI], 6.11-8.03) and late preterm preeclampsia
(OR, 2.82; 95% CI, 2.38-3.34) in the same pregnancy and weakly associated with
term preeclampsia (OR, 1.16; 95% CI, 1.06-1.27), but they were not associated
with gestational hypertension (OR, 1.07; 95% CI, 0.92-1.25). Association
strengths were consistent across heart defect types. Offspring congenital heart
defects in a previous pregnancy were also strongly associated with preterm
preeclampsia in subsequent pregnancies (early preterm preeclampsia: OR, 2.37; 95%
CI, 1.68-3.34; late preterm preeclampsia: OR, 2.04; 95% CI, 1.52-2.75) but were
only modestly associated with term preeclampsia and not associated with
gestational hypertension. Similarly, preterm preeclampsia in a previous
pregnancy, but not term preeclampsia or gestational hypertension, was associated
with offspring congenital heart defects in later pregnancies (early preterm
preeclampsia: OR, 7.91; 95% CI, 6.06-10.3; late preterm preeclampsia: OR, 2.83;
95% CI, 2.11-3.79; term preeclampsia: OR, 0.98; 95% CI, 0.88-1.10; gestational
hypertension: OR, 1.13; 95% CI, 0.92-1.38). CONCLUSIONS: Linked
pathophysiological mechanisms may be involved in some congenital heart defects
and preterm preeclampsia. The strong associations across pregnancies support a
predominantly maternal origin of effect.
PMID- 28424222
TI - Randomized Comparison of Paclitaxel-Eluting Balloon and Stenting Versus Plain
Balloon Plus Stenting Versus Directional Atherectomy for Femoral Artery Disease
(ISAR-STATH).
AB - BACKGROUND: Atherosclerosis in the superficial femoral artery is common in
patients suffering from peripheral artery disease. Paclitaxel-eluting balloon
(PEB) angioplasty, stenting, and directional atherectomy (DA) have provided new
options for the treatment of superficial femoral artery disease; however, the
comparative efficacy of these interventional strategies remains uncertain.
METHODS: One hundred and fifty-five patients with symptomatic peripheral artery
disease due to de novo superficial femoral artery stenotic or occlusive lesions
were randomized to treatment with plain balloon angioplasty (BA) followed by PEB
angioplasty and stenting (n=48), BA and stenting (n=52), or DA with distal
protection and bailout stenting (n=55). The primary end point of the study was
percentage diameter stenosis after 6 months measured by angiography. Other end
points included target lesion revascularization, thrombosis, ipsilateral
amputation, binary restenosis, and all-cause mortality at 6 and 24 months.
RESULTS: Baseline and lesion characteristics were comparable in all groups with a
mean lesion length of 65.9+/-46.8 mm and 56% total occlusions. At 6 months
angiography, the percent diameter stenosis was significantly lower in patients
treated by PEB angioplasty and stenting (34+/-31%) as compared with BA
angioplasty and stenting (56+/-29%, P=0.009) or DA (55+/-29%, P=0.007).
Similarly, binary restenosis was significantly lower after treatment with PEB and
stenting as compared with BA and stenting or DA. Clinical follow-up at 24 months
revealed a lower risk for target lesion revascularization after PEB angioplasty
and stenting as compared with BA and stenting or DA. We found no difference in
terms of target lesion thrombosis and mortality among groups, and no patient
underwent amputation. CONCLUSIONS: Treatment of de novo superficial femoral
artery lesions with PEB angioplasty and stenting is superior to BA angioplasty
and stenting or DA in terms of angiographic diameter stenosis at 6 months and
target lesion revascularization at 24 months. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00986752.
PMID- 28424224
TI - Novel Strategies to Reduce Femoropopliteal Restenosis: Low-Dose Paclitaxel-Coated
Balloons and Paclitaxel-Coated Balloons Plus Stenting.
PMID- 28424223
TI - Low-Dose Paclitaxel-Coated Versus Uncoated Percutaneous Transluminal Balloon
Angioplasty for Femoropopliteal Peripheral Artery Disease: One-Year Results of
the ILLUMENATE European Randomized Clinical Trial (Randomized Trial of a Novel
Paclitaxel-Coated Percutaneous Angioplasty Balloon).
AB - BACKGROUND: Numerous studies have reported favorable outcomes using drug-coated
balloons (DCBs) for treatment of symptomatic peripheral artery disease of the
superficial femoral and popliteal arteries. However, the treatment effect
compared with an uncoated balloon has differed greatly among the randomized
trials, with better outcomes observed with higher-dose DCBs. This European trial
was designed to assess the safety and effectiveness of a next-generation low-dose
(2-ug/mm2 surface dose of paclitaxel) DCB. METHODS: This was a prospective,
randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to
treatment with a low-dose DCB or an uncoated percutaneous transluminal
angioplasty (PTA) balloon. The primary safety end point was a composite of
freedom from device- and procedure-related death through 30 days after the
procedure and freedom from target limb major amputation and clinically driven
target lesion revascularization through 12 months after the procedure. The
primary effectiveness end point was primary patency at 12 months. RESULTS:
Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or
uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation.
Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented
total occlusions, respectively. The primary safety end point was met, and
superiority was demonstrated; freedom from a primary safety event was 94.1% (193
of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95%
confidence interval, 0.9%-23.0%). The primary effectiveness end point was met,
and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40
of 66]; P<0.001). Outcomes with DCB were also superior to PTA per the Kaplan
Meier estimate for primary patency (89.0% versus 65.0% at 365 days; log-rank
P<0.001) and for rates of clinically driven target lesion revascularization (5.9%
versus 16.7%; P=0.014). CONCLUSIONS: Superiority with a low-dose DCB for
femoropopliteal interventions was demonstrated over PTA for both the safety and
effectiveness end points. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01858363.
PMID- 28424225
TI - Quantitative Assessment of Airway Pathology in Subjects With COPD Using Low-Dose
High-Resolution Computed Tomography.
AB - BACKGROUND: The purpose of this study was to correlate airway parameters of COPD
determined by low-dose high-resolution computed tomography (HRCT) with pulmonary
function testing (PFT) results. METHODS: PFT data were collected for subjects
with COPD and healthy controls. All subjects received inspiratory and expiratory
phase low-dose HRCT. Bronchi in the apical segment of the right upper lobe (RB1),
posterior segment of the right lower lobe (RB6), and lower lingual segment of the
left upper lobe (LB5) were the target bronchi. Software automatically calculated
airway wall area, inner area, and airway wall area percentage (percentage wall
area for bronchial external area). RESULTS: A total of 75 COPD and 20 control
subjects were included. The subjects with COPD were classified according to COPD
stage, with 20 grade I, II, and III subjects, respectively, and 15 grade IV
subjects. In COPD grade II, residual volume/total lung capacity was negatively
correlated with airway wall area in LB5 (r = -0.51). In COPD grade III, FVC was
negatively correlated with airway wall area percentage in LB5 (r = -0.49) but
positively correlated with airway wall area in RB6 (r = 0.52); percent-of
predicted FEV1 was negatively correlated with airway wall area percentage in RB1
(r = -0.49); residual volume was negatively correlated with airway wall area (r =
-0.47), and total lung capacity was negatively correlated with airway wall area
in RB1 (r = -0.52) (all, P < .001). CONCLUSIONS: The results of this study
suggest that airway parameters in different COPD grades have no uniform tendency
of correlation with PFT, but some HRCT parameters are correlated to some PFT
parameters.
PMID- 28424226
TI - Objective Measurement of Adherence to Out-Patient Airway Clearance Therapy by
High-Frequency Chest Wall Compression in Cystic Fibrosis.
AB - BACKGROUND: Objective measures of adherence to high-frequency chest wall
compression (HFCWC), a form of airway clearance therapy for patients with cystic
fibrosis, are lacking. We used a novel electronic monitoring device integrated
into an HFCWC vest to measure adherence compared with self-reported adherence. We
determined factors that influenced adherence and how adherence correlated with
baseline pulmonary function and pulmonary exacerbations. METHODS: Data were
collected by direct measurement of date, time of day, and duration of HFCWC use
to determine the number of daily treatments and daily duration of treatments.
Chart review provided prescribed airway clearance therapy treatment and
demographic and clinical information. Subject and caregiver report of the daily
number of airway clearance therapy treatments was obtained by telephone
interviews. Analysis used 2-sample and paired t test, analysis of variance, and
linear regression. RESULTS: Average adherence was 69%. Adherence was highest in
children (82%, P = .02) and those receiving assistance with treatment (82%, P <
.001). Subjects overestimated therapy duration from a mean +/- SD of 127 +/- 169%
by adults to 19.2 +/- 26.3% by parents or guardians of children. Average
adherence decreased with increasing prescribed therapy time (P = .02). Average
daily therapy time and adherence had significant positive associations with
baseline FEV1 percent of predicted (P = .02 and P = .02, respectively) and
negative associations with pulmonary exacerbations during the pre-study period
and at baseline (P = .044 and P = .02, respectively). CONCLUSIONS: Greater
adherence to HFCWC measured directly by a novel recorder was associated with
better baseline pulmonary function and fewer exacerbations in the pre-study and
baseline period. Adherence decreased with age and prescribed therapy time and
increased with therapy assistance. Self-report overestimation is large and thus
not an accurate measure of adherence.
PMID- 28424227
TI - ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple
Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms.
AB - Breast cancer is a major cause of cancer-related death. TNF-related apoptosis
inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a
subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small
molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has
entered clinical trials in advanced cancers. Here, we show that ONC201 is
efficacious against both TNBC and non-TNBC cells (n = 13). A subset of TNBC and
non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines,
ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by
TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to
in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested
(6/8), ONC201 has an antiproliferative effect but does not induce apoptosis.
ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the
G1 phase of the cell cycle. pRb expression is associated with sensitivity to the
antiproliferative effects of ONC201, and the compound synergizes with taxanes in
less sensitive cells. All non-TNBC cells (n = 5) are growth inhibited following
ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n = 2)
shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL
independent. Our data demonstrate that ONC201 has potent antiproliferative and
proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL
dependent and TRAIL-independent mechanisms. These findings develop a preclinical
rationale for developing ONC201 as a single agent and/or in combination with
approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290-8. (c)2017
AACR.
PMID- 28424228
TI - Pseudomonas doesn't mind a dunking.
AB - A new study explains Pseudomonas aeruginosa's strong resistance to osmotic down
shock.
PMID- 28424230
TI - A quiet revolution in organ transplant ethics.
AB - A quiet revolution is occurring in the field of transplantation. Traditionally,
transplants have involved solid organs such as the kidney, heart and liver which
are transplanted to prevent recipients from dying. Now transplants are being done
of the face, hand, uterus, penis and larynx that aim at improving a recipient's
quality of life. The shift away from saving lives to seeking to make them better
requires a shift in the ethical thinking that has long formed the foundation of
organ transplantation. The addition of new forms of transplants requires doctors,
patients, regulators and the public to rethink the risk and benefit ratio
represented by trade-offs between saving life, extending life and risking the
loss of life to achieve improvements in the quality of life.
PMID- 28424229
TI - Tension-activated channels in the mechanism of osmotic fitness in Pseudomonas
aeruginosa.
AB - Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional
ability to adapt to a range of environments. Part of its adaptive potential is
the ability to survive drastic osmolarity changes. Upon a sudden dilution of
external medium, such as during exposure to rain, bacteria evade mechanical
rupture by engaging tension-activated channels that act as osmolyte release
valves. In this study, we compare fast osmotic permeability responses in
suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow
experiments and provide electrophysiological descriptions of osmotic-release
channels in PA. Using osmotic dilution experiments, we first show that PA
tolerates a broader range of shocks than EC. We record the kinetics of cell
equilibration reported by light scattering responses to osmotic up- and down
shocks. PA exhibits a lower water permeability and faster osmolyte release rates
during large osmotic dilutions than EC, which correlates with better survival. To
directly characterize the PA tension-activated channels, we generate giant
spheroplasts from this microorganism and record current responses in excised
patches. Unlike EC, which relies primarily on two types of channels, EcMscS and
EcMscL, to generate a distinctive two-wave pressure ramp response, PA exhibits a
more gradual response that is dominated by MscL-type channels. Genome analysis,
cloning, and expression reveal that PA possesses one MscL-type (PaMscL) and two
MscS-type (PaMscS-1 and 2) proteins. In EC spheroplasts, both PaMscS channels
exhibit a slightly earlier activation by pressure compared with EcMscS. Unitary
currents reveal that PaMscS-2 has a smaller conductance, higher anionic
preference, stronger inactivation, and slower recovery compared with PaMscS-1. We
conclude that PA relies on MscL as the major valve defining a high rate of
osmolyte release sufficient to curb osmotic swelling under extreme shocks, but it
still requires MscS-type channels with a strong propensity to inactivation to
properly terminate massive permeability response.
PMID- 28424231
TI - Mroh1, a lysosomal regulator localized by WASH-generated actin.
AB - The steps leading to constitutive exocytosis are poorly understood. In
Dictyostelium WASH complex mutants, exocytosis is blocked, so cells that take up
fluorescent dextran from the medium retain it and remain fluorescent. Here, we
establish a FACS-based method to select cells that retain fluorescent dextran,
allowing identification of mutants with disrupted exocytosis. Screening a pool of
random mutants identified members of the WASH complex, as expected, and multiple
mutants in the conserved HEAT-repeat-containing protein Mroh1. In mroh1 mutants,
endosomes develop normally until the stage where lysosomes neutralize to
postlysosomes, but thereafter the WASH complex is recycled inefficiently, and
subsequent exocytosis is substantially delayed. Mroh1 protein localizes to
lysosomes in mammalian and Dictyostelium cells. In Dictyostelium, it accumulates
on lysosomes as they mature and is removed, together with the WASH complex,
shortly before the postlysosomes are exocytosed. WASH-generated F-actin is
required for correct subcellular localization; in WASH complex mutants, and
immediately after latrunculin treatment, Mroh1 relocalizes from the cytoplasm to
small vesicles. Thus, Mroh1 is involved in a late and hitherto undefined actin
dependent step in exocytosis.
PMID- 28424232
TI - Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during
Drosophila wound healing.
AB - Cell-cell fusion is widely observed during development and disease, and imposes a
dramatic change on participating cells. Cell fusion should be tightly controlled,
but the underlying mechanism is poorly understood. Here, we found that the
JAK/STAT pathway suppressed cell fusion during wound healing in the Drosophila
larval epidermis, restricting cell fusion to the vicinity of the wound. In the
absence of JAK/STAT signaling, a large syncytium containing a 3-fold higher
number of nuclei than observed in wild-type tissue formed in wounded epidermis.
The JAK/STAT ligand-encoding genes upd2 and upd3 were transcriptionally induced
by wounding, and were required for suppressing excess cell fusion. JNK (also
known as Basket in flies) was activated in the wound vicinity and activity peaked
at ~8 h after injury, whereas JAK/STAT signaling was activated in an adjoining
concentric ring and activity peaked at a later stage. Cell fusion occurred
primarily in the wound vicinity, where JAK/STAT activation was suppressed by
fusion-inducing JNK signaling. JAK/STAT signaling was both necessary and
sufficient for the induction of betaPS integrin (also known as Myospheroid)
expression, suggesting that the suppression of cell fusion was mediated at least
in part by integrin protein.
PMID- 28424233
TI - CLUH couples mitochondrial distribution to the energetic and metabolic status.
AB - Mitochondrial dynamics and distribution are critical for supplying ATP in
response to energy demand. CLUH is a protein involved in mitochondrial
distribution whose dysfunction leads to mitochondrial clustering, the metabolic
consequences of which remain unknown. To gain insight into the role of CLUH on
mitochondrial energy production and cellular metabolism, we have generated CLUH
knockout cells using CRISPR/Cas9. Mitochondrial clustering was associated with a
smaller cell size and with decreased abundance of respiratory complexes,
resulting in oxidative phosphorylation (OXPHOS) defects. This energetic
impairment was found to be due to the alteration of mitochondrial translation and
to a metabolic shift towards glucose dependency. Metabolomic profiling by mass
spectroscopy revealed an increase in the concentration of some amino acids,
indicating a dysfunctional Krebs cycle, and increased palmitoylcarnitine
concentration, indicating an alteration of fatty acid oxidation, and a dramatic
decrease in the concentrations of phosphatidylcholine and sphingomyeline,
consistent with the decreased cell size. Taken together, our study establishes a
clear function for CLUH in coupling mitochondrial distribution to the control of
cell energetic and metabolic status.
PMID- 28424234
TI - BRAF V600 mutation detection in melanoma: a comparison of two laboratory testing
methods.
AB - AIMS: The assessment of B-raf proto-oncogene, serine/threonine kinase (BRAF) gene
status is now standard practice in patients diagnosed with metastatic melanoma
with its presence predicting a clinical response to treatment with BRAF
inhibitors. The gold standard in determining BRAF status is currently by DNA
based methods. More recently, a BRAF V600E antibody has been developed. We aim to
investigate whether immunohistochemical detection of BRAF mutation is a suitable
alternative to molecular testing by polymerase chain reaction (PCR). METHODS: We
assessed the incidence of BRAF mutation in our cohort of 132 patients, as
determined by PCR, as well as examining clinical and histopathological features.
We investigated the sensitivity and specificity of the anti-BRAF V600E VE1 clone
antibody in detecting the presence of the BRAF V600E mutation in 122 cases deemed
suitable for testing. RESULTS: The incidence of BRAF mutation in our cohort was
28.8% (38/132). Patients with the BRAF mutation were found to be significantly
younger at age of diagnosis. BRAF-mutated melanomas tended to be thinner and more
mitotically active. The antibody showed a sensitivity of 86.1% with a specificity
of 96.9%. The positive predictive value was 96.9%; the negative predictive value
was 94.4%. The concordance rate between PCR and immunohistochemical BRAF status
was 95.1% (116/122). CONCLUSIONS: The rate of BRAF mutation in our cohort (28.8%)
was lower than international published rates of 40%-60%. This may reflect ethnic
or geographic differences within population cohorts. The high concordance rate of
PCR and immunohistochemical methods in determining BRAF status suggests that
immunohistochemistry is potentially a viable, cost-effective alternative to PCR
testing and suitable as a screening test for the BRAF mutation.
PMID- 28424235
TI - Increased alloimmunisation and transfusion reaction reporting in patients with
solid-phase panreactivity.
AB - BACKGROUND: Automated solid-phase antibody screening uses red blood cell (RBC)
membranes immobilised on polystyrene test wells to detect RBC specific
antibodies. Despite its time-saving and labour-saving benefits, this method
produces a higher rate of nonspecific reactivity compared with manual screening.
Solid-phase panreactivity (SPP) is characterised by panreactivity (ie, all test
cells reacting) in solid-phase testing accompanied by a negative autocontrol and
a lack of reactivity when the same screening cells are tested in tube. The
mechanisms underlying SPP and its clinical significance remain unclear. The goals
of this study were to describe the prevalence of SPP at our institution and
determine the alloimmunisation and transfusion reaction rates within this
population. METHODS: Data were collected on all patients undergoing type and
screen testing over a 6-year period. Study patients undergoing subsequent
transfusion were evaluated for reported transfusion reactions and development of
new alloantibodies. RESULTS: Of the 76 051 patients studied, 0.7% demonstrated
SPP of which 11% developed new alloantibodies. The transfusion reaction reporting
rate among patients with SPP was 2%. CONCLUSIONS: Our data suggest that patients
with SPP have higher rates of reported transfusion reactions and alloantibody
development compared with those without SPP.
PMID- 28424236
TI - Hyalinizing trabecular tumour of the thyroid: fine-needle aspiration cytological
diagnosis and correlation with histology.
AB - Hyalinizing trabecular tumour (HTT) is a rare thyroid neoplasm of follicular cell
origin characterised by a trabecular growth pattern and prominent intratrabecular
and intertrabecular hyalinisation. These peculiar histological features allow the
prompt recognition of this neoplasm in surgical specimens. However, cytological
diagnosis of HTT remains elusive and misleading because of overlapping
characteristics with other thyroid tumours, particularly papillary thyroid
carcinoma (PTC), medullary thyroid carcinoma (MTC) and the newly described non
invasive follicular thyroid neoplasm with papillary-like nuclear features
(NIFTP). Nevertheless, the proper recognition of this neoplasm on preoperative
cytological preparations is important to avoid unnecessary overtreatment of this
indolent lesion. A thorough review of the literature has revealed that the
correct diagnosis of HTT in cytological smears is achieved in only 8% of cases.
In a further 6% of cases, diagnostic doubt has been indicated. Sixty percent of
published cases of HTT have been misdiagnosed as suggestive, suspicious or
positive for PTC. These findings underline the difficulties of a cytological
based diagnosis of such entity. In this article we review the cytomorphological
features of HTT and their correlation to histological features to provide the
reader with the tools to improve diagnostic performance in the identification of
HTT on preoperative cytology.
PMID- 28424237
TI - Absence of SMAD9v90m mutation in juvenile polyposis syndrome.
PMID- 28424238
TI - IL-20 Signaling in Activated Human Neutrophils Inhibits Neutrophil Migration and
Function.
AB - Neutrophils possess multiple antimicrobial mechanisms that are critical for
protection of the host against infection with extracellular microbes, such as the
bacterial pathogen Staphylococcus aureus Recruitment and activation of
neutrophils at sites of infection are driven by cytokine and chemokine signals
that directly target neutrophils via specific cell surface receptors. The IL-20
subfamily of cytokines has been reported to act at epithelial sites and
contribute to psoriasis, wound healing, and anti-inflammatory effects during S.
aureus infection. However, the ability of these cytokines to directly affect
neutrophil function remains incompletely understood. In this article, we show
that human neutrophils altered their expression of IL-20R chains upon migration
and activation in vivo and in vitro. Such activation of neutrophils under
conditions mimicking infection with S. aureus conferred responsiveness to IL-20
that manifested as modification of actin polymerization and inhibition of a broad
range of actin-dependent functions, including phagocytosis, granule exocytosis,
and migration. Consistent with the previously described homeostatic and anti
inflammatory properties of IL-20 on epithelial cells, the current study provides
evidence that IL-20 directly targets and inhibits key inflammatory functions of
neutrophils during infection with S. aureus.
PMID- 28424239
TI - AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality.
AB - The absent in melanoma 2 (AIM2) inflammasome plays an important role in many
viral and bacterial infections, but very little is known about its role in RNA
virus infection, including influenza A virus (IAV). In this study, we have
designed in vivo and in vitro studies to determine the role of AIM2 in infections
with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV
infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase
1 activation and release of cleaved IL-1beta in the lung, which was significantly
reduced in AIM2-deficient mice. Interestingly, AIM2 deficiency did not affect the
transcription of caspase-1 and IL-1beta. In addition, AIM2-deficient mice
exhibited attenuated lung injury and significantly improved survival against IAV
challenges, but did not alter viral burden in the lung. However, AIM2 deficiency
did not seem to affect adaptive immune response against IAV infections.
Furthermore, experiments with AIM2-specific small interfering RNA-treated and
AIM2-deficient human and mouse lung alveolar macrophages and type II cells
indicated a macrophage-specific function of AIM2 in regulation of IAV-stimulated
proinflammatory response. Collectively, our results demonstrate that influenza
infection activates the AIM2 inflammasome, which plays a critical role in IAV
induced lung injury and mortality. AIM2 might serve as a therapeutic target for
combating influenza-associated morbidity and mortality without compromising the
host antiviral responses.
PMID- 28424240
TI - The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation.
AB - Histone acetyltransferases (HATs) regulate inducible transcription in multiple
cellular processes and during inflammatory and immune response. However, the
functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily
conserved HAT from yeast to human, in immune regulation remain unappreciated. In
this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene)
specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and
demonstrated that Gcn5 plays important roles in multiple stages of T cell
functions including development, clonal expansion, and differentiation. Loss of
Gcn5 functions impaired T cell proliferation, IL-2 production, and Th1/Th17, but
not Th2 and regulatory T cell differentiation. Gcn5 is recruited onto the il-2
promoter by interacting with the NFAT in T cells upon TCR stimulation.
Interestingly, instead of directly acetylating NFAT, Gcn5 catalyzes histone H3
lysine H9 acetylation to promote IL-2 production. T cell-specific suppression of
Gcn5 partially protected mice from myelin oligodendrocyte glycoprotein-induced
experimental autoimmune encephalomyelitis, an experimental model for human
multiple sclerosis. Our study reveals previously unknown physiological functions
for Gcn5 and a molecular mechanism underlying these functions in regulating T
cell immunity. Hence Gcn5 may be an important new target for autoimmune disease
therapy.
PMID- 28424241
TI - Microbiota-Induced Antibodies Are Essential for Host Inflammatory Responsiveness
to Sterile and Infectious Stimuli.
AB - The indigenous intestinal microbiota is frequently considered an additional major
organ of the human body and exerts profound immunomodulating activities. Germ
free (GF) mice display a significantly different inflammatory responsiveness
pattern compared with conventional (CV) mice, and this was dubbed a
"hyporesponsive phenotype." Taking into account that the deposition of immune
complexes is a major event in acute inflammation and that GF mice have a distinct
Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig
repertoire interferes with the inflammatory responsiveness of GF mice. We found
that serum transfer from CV naive mice was capable of reversing the inflammatory
hyporesponsiveness of GF mice in sterile inflammatory injury induced by
intestinal ischemia and reperfusion, as well as in a model of lung infection by
Klebsiella pneumoniae Transferring serum from Ig-deficient mice to GF animals did
not alter their response to inflammatory insult; however, injecting purified Abs
from CV animals restored inflammatory responsiveness in GF mice, suggesting that
natural Abs present in serum were responsible for altering GF responsiveness.
Mechanistically, injection of serum and Ig from CV mice into GF animals restored
IgG deposition, leukocyte influx, NF-kappaB activation, and proinflammatory gene
expression in inflamed tissues and concomitantly downregulated annexin-1 and IL
10 production. Thus, our data show that microbiota-induced natural Abs are
pivotal for host inflammatory responsiveness to sterile and infectious insults.
PMID- 28424242
TI - mTORC1 Promotes T-bet Phosphorylation To Regulate Th1 Differentiation.
AB - CD4+ T cells lacking the mTORC1 activator Rheb fail to secrete IFN-gamma under
Th1 polarizing conditions. We hypothesized that this phenotype is due to defects
in regulation of the canonical Th1 transcription factor T-bet at the level of
protein phosphorylation downstream of mTORC1. To test this hypothesis, we
employed targeted mass-spectrometry proteomic analysis-multiple reaction
monitoring mass spectrometry. We used this method to detect and quantify
predicted phosphopeptides derived from T-bet. By analyzing activated murine wild
type and Rheb-deficient CD4+ T cells, as well as murine CD4+ T cells activated in
the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to
identify six T-bet phosphorylation sites. Five of these are novel, and four sites
are consistently dephosphorylated in both Rheb-deficient CD4+ T cells and T cells
treated with rapamycin, suggesting mTORC1 signaling controls their
phosphorylation. Alanine mutagenesis of each of the six phosphorylation sites was
tested for the ability to impair IFN-gamma expression. Single phosphorylation
site mutants still support induction of IFN-gamma expression; however,
simultaneous mutation of three of the mTORC1-dependent sites results in
significantly reduced IFN-gamma expression. The reduced activity of the triple
mutant T-bet is associated with its failure to recruit chromatin remodeling
complexes to the Ifng gene promoter. These results establish a novel mechanism by
which mTORC1 regulates Th1 differentiation, through control of T-bet
phosphorylation.
PMID- 28424243
TI - Nutrition and High-Flow Nasal Cannula Respiratory Support in Children With
Bronchiolitis.
AB - OBJECTIVES: No guidelines are available regarding initiation of enteral nutrition
in children with bronchiolitis on high-flow nasal cannula (HFNC) support. We
hypothesized that the incidence of feeding-related adverse events (AEs) would not
be associated with HFNC support. METHODS: This retrospective study included
children <=24 months old with bronchiolitis receiving HFNC in a PICU from
September 2013 through April 2014. Data included demographics, respiratory
support during feeding, and feeding-related AEs. Feeding-related AEs were
extracted from nursing documentation and defined as respiratory distress or
emesis. Feed route and maximum HFNC delivery were recorded in 8-hour shifts (6 am
2 pm, 2 pm-10 pm, and 10 pm-6 am). RESULTS: 70 children were included, with a
median age of 5 (interquartile range [IQR] 2-10) months. HFNC delivery at feed
initiation varied widely, and AEs related to feeding occurred rarely. Children
were fed in 501 of 794 (63%) of nursing shifts, with AEs documented in only 29 of
501 (5.8%) of those shifts. The incidence of AEs at varying levels of respiratory
support did not differ (P = .092). Children in the "early feeding" (fed within
first 2 shifts) group (n = 22) had a shorter PICU length of stay (2.2 days [IQR
1.4-3.9] vs 3.2 [IQR 2.5-5.3], P = .006) and shorter duration of HFNC use (26.0
hours [IQR 15.8-57.0] vs 53.5 [IQR 37.0-84.8], P = .002), compared with children
in the "late feeding" group (n = 48). CONCLUSIONS: In this small, single
institution patient cohort, feeding-related AEs were rare and not related to the
delivered level of respiratory support.
PMID- 28424244
TI - Children With Bronchiolitis on High-Flow Nasal Cannula: To Feed or Not Feed, That
Is Not the Only Question.
PMID- 28424245
TI - Oral Nutrition in Children With Bronchiolitis on High-Flow Nasal Cannula Is Well
Tolerated.
AB - OBJECTIVES: To determine the incidence of aspiration-related respiratory failure
and nutrition interruptions in children with bronchiolitis on high-flow nasal
cannula (HFNC) receiving enteral nutrition. METHODS: We performed a single
center, prospective, observational cohort study within a 313-bed tertiary medical
center from January through December 2015. We included term children 1 month to 2
years of age without comorbid bacterial pneumonia or chronic medical conditions
who were diagnosed with bronchiolitis while receiving HFNC and enteral nutrition.
Primary outcomes were incidence of aspiration-related respiratory failure and
nutrition interruptions. Secondary outcomes were duration of HFNC therapy, length
of stay, and nutrition characteristics. RESULTS: Of the 344 children admitted
with bronchiolitis, 132 met the inclusion criteria. Ninety-seven percent received
enteral nutrition by mouth and 3% by nasogastric tube. HFNC flow rates at the
time of nutrition initiation ranged between 4 and 13 L per minute (0.3-1.9 L/kg
per minute) and respiratory rates from 18 to 69 breaths per minute. One (0.8%)
subject had aspiration-related respiratory failure and 12 (9.1%) experienced
nutrition interruptions. Children with interruptions in nutrition had a longer
length of stay by 2.5 days (P < .01) and received an additional day of HFNC
therapy (P < .01). By discharge, 55 (42%) children achieved all nutritional
goals: caloric, volume, and protein. Children admitted overnight had an increased
incidence of delay to nutrition initiation (30% vs 11%; P < .01). CONCLUSIONS: We
observed a low incidence of aspiration-related respiratory failure in term
children with bronchiolitis on HFNC receiving enteral nutrition. Oral nutrition
was tolerated across a range of HFNC flow and respiratory rates, suggesting the
practice of withholding nutrition in this population is unsupported.
PMID- 28424247
TI - Location in the spleen dictates the function of murine neutrophils.
AB - In this issue of JEM, Deniset et al. (https://doi.org/10.1084/jem.20161621)
provide new data that extend our knowledge on the mechanisms whereby
Streptococcus pneumoniae is cleared by the spleen. The authors identify novel
populations of murine splenic neutrophils that localize in the red pulp and the
marginal zone. During the acute phases of S. pneumoniae infection, these
populations of splenic neutrophils act in concert with specialized macrophage and
B cell populations to provide very rapid innate immune protection.
PMID- 28424246
TI - Enteropathy-associated T cell lymphoma subtypes are characterized by loss of
function of SETD2.
AB - Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common,
neoplastic complication of celiac disease. Here, we defined the genetic landscape
of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most
frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the
most frequently mutated pathway, with frequent mutations in STAT5B as well as
JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT
Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell
lymphoma) had highly overlapping genetic alterations indicating shared mechanisms
underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by
developing a T cell-specific knockout mouse. These mice manifested an expansion
of gammadelta T cells, indicating novel roles for SETD2 in T cell development and
lymphomagenesis. Our data render the most comprehensive genetic portrait yet of
this uncommon but lethal disease and may inform future classification schemes.
PMID- 28424248
TI - Splenic Ly6Ghigh mature and Ly6Gint immature neutrophils contribute to
eradication of S. pneumoniae.
AB - The spleen plays an integral protective role against encapsulated bacterial
infections. Our understanding of the associated mechanisms is limited to thymus
independent (TI) antibody production by the marginal zone (MZ) B cells, leaving
the contribution of other splenic compartments such as the red pulp (RP) largely
unexplored despite asplenic patients succumbing to the infection in the first 24
h, suggesting important antibody-independent mechanisms. In this study, using
time-lapse intravital imaging of the spleen, we identify a tropism for
Streptococcus pneumoniae in this organ mediated by tissue-resident MZ and RP
macrophages and a protective role for two distinct splenic neutrophil populations
(Ly6Ghi and Ly6Gintermediate) residing in the splenic RP. Splenic mature
neutrophils mediated pneumococcal clearance in the spleen by plucking bacteria
off the surface of RP macrophages that caught the majority of bacteria in a
complement-dependent manner. This neutrophil phagocytic capacity was further
enhanced after TI antibody production. Resident immature neutrophils
(Ly6Gintermediate) in the spleen undergo emergency proliferation and mobilization
from their splenic niche after pneumococcal stimulation to increase the effector
mature neutrophil pool. We demonstrate that splenic neutrophils together with two
macrophage populations and MZ B cells regulate systemic S. pneumoniae clearance
through complementary mechanisms.
PMID- 28424249
TI - Lignocellulose pretreatment in a fungus-cultivating termite.
AB - Depolymerizing lignin, the complex phenolic polymer fortifying plant cell walls,
is an essential but challenging starting point for the lignocellulosics
industries. The variety of ether- and carbon-carbon interunit linkages produced
via radical coupling during lignification limit chemical and biological
depolymerization efficiency. In an ancient fungus-cultivating termite system, we
reveal unprecedentedly rapid lignin depolymerization and degradation by combining
laboratory feeding experiments, lignocellulosic compositional measurements,
electron microscopy, 2D-NMR, and thermochemolysis. In a gut transit time of under
3.5 h, in young worker termites, poplar lignin sidechains are extensively cleaved
and the polymer is significantly depleted, leaving a residue almost completely
devoid of various condensed units that are traditionally recognized to be the
most recalcitrant. Subsequently, the fungus-comb microbiome preferentially uses
xylose and cleaves polysaccharides, thus facilitating final utilization of easily
digestible oligosaccharides by old worker termites. This complementary symbiotic
pretreatment process in the fungus-growing termite symbiosis reveals a previously
unappreciated natural system for efficient lignocellulose degradation.
PMID- 28424250
TI - Unifying mechanism for different fibrotic diseases.
AB - Fibrotic diseases are not well-understood. They represent a number of different
diseases that are characterized by the development of severe organ fibrosis
without any obvious cause, such as the devastating diseases idiopathic pulmonary
fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable
with endstage cancer and are uncurable. Given the phenotypic differences, it was
assumed that the different fibrotic diseases also have different pathomechanisms.
Here, we demonstrate that many endstage fibrotic diseases, including IPF;
scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and
nonalcoholic steatohepatosis converge in the activation of the AP1 transcription
factor c-JUN in the pathologic fibroblasts. Expression of the related AP1
transcription factor FRA2 was restricted to pulmonary artery hypertension.
Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple
organs and steatohepatosis, which was dependent on sustained c-Jun expression.
Single cell mass cytometry revealed that c-Jun activates multiple signaling
pathways in mice, including pAkt and CD47, which were also induced in human
disease. alphaCD47 antibody treatment and VEGF or PI3K inhibition reversed
various organ c-Jun-mediated fibroses in vivo. These data suggest that c-JUN is a
central molecular mediator of most fibrotic conditions.
PMID- 28424251
TI - Nuclear Shp2 directs normal embryo implantation via facilitating the ERalpha
tyrosine phosphorylation by the Src kinase.
AB - Estrogen and progesterone coupled with locally produced signaling molecules are
essential for embryo implantation. However, the hierarchical landscape of the
molecular pathways that governs this process remains largely unexplored. Here we
show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK
signaling, is predominately localized in the nuclei in the periimplantation mouse
uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor
(PR) expression and progesterone resistance, which derails normal uterine
receptivity, leading to complete implantation failure in mice. Notably, the PR
expression defects are attributed to the limited estrogen receptor alpha
(ERalpha) activation in uterine stroma. Further analysis reveals that nuclear
Shp2, rather than cytosolic Shp2, promotes the ERalpha transcription activity.
This function is achieved by enhancing the Src kinase-mediated ERalpha tyrosine
phosphorylation, which facilitates ERalpha binding to Pgr promoter in an ERK
independent manner in periimplantation uteri. Besides uncovering a regulatory
mechanism, this study could be clinically relevant to dysfunctional ERalpha
caused endometrial disorders in women.
PMID- 28424252
TI - Comparison of Saramis 4.12 and IVD 3.0 Vitek MS Matrix-Assisted Laser Desorption
Ionization-Time of Flight Mass Spectrometry for Identification of Mycobacteria
from Solid and Liquid Culture Media.
AB - During the last decade, many investigators have studied matrix-assisted laser
desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for
identification of mycobacteria. Diverse and contradictory results indicated that
optimal level for routine testing has not been reached yet. This work aimed to
assess Vitek MS through two distinct versions, Saramis v4.12 RUO and the IVD
v3.0, under conditions close to routine laboratory practice. Overall, 111
mycobacterial isolates were subjected to protein extraction and same spectra were
matched against both databases. The IVD v3.0 database proved to be superior to
Saramis v4.12 and its identification rates remarkably increased, from 67% to 94%
for isolates grown on Middlebrook 7H10 solid medium and from 62% to 91% for
isolates grown on mycobacterial growth indicator tube (MGIT) liquid medium. With
this new version, IVD v3.0, MALDI-TOF MS might be integrated into routine
clinical diagnostics, although molecular techniques remain mandatory in some
cases.
PMID- 28424253
TI - Identification of Acute HIV-1 Infection by Hologic Aptima HIV-1 RNA Qualitative
Assay.
AB - The Hologic Aptima HIV-1 Qualitative RNA assay was used in a rigorous screening
approach designed to identify individuals at the earliest stage of HIV-1
infection for enrollment into subsequent studies of cellular and viral events in
early infection (RV 217/Early Capture HIV Cohort [ECHO] study). Volunteers at
high risk for HIV-1 infection were recruited from study sites in Thailand,
Tanzania, Uganda, and Kenya with high HIV-1 prevalence rates among the
populations examined. Small-volume blood samples were collected by finger stick
at twice-weekly intervals and tested with the Aptima assay. Participants with
reactive Aptima test results were contacted immediately for entry into a more
comprehensive follow-up schedule with frequent blood draws. Evaluation of the
Aptima test prior to use in this study showed a detection sensitivity of 5.5
copies/ml (50%), with all major HIV-1 subtypes detected. A total of 54,306
specimens from 1,112 volunteers were examined during the initial study period
(August 2009 to November 2010); 27 individuals were identified as converting from
uninfected to infected status. A sporadic reactive Aptima signal was observed in
HIV-1-infected individuals under antiretroviral therapy. Occasional false
reactive Aptima results in uninfected individuals, or nonreactive results in HIV
1-infected individuals not on therapy, were observed and used to calculate assay
sensitivity and specificity. The sensitivity and specificity of the Aptima assay
were 99.03% and 99.23%, respectively; positive and negative predictive values
were 92.01% and 99.91%, respectively. Conversion from HIV-1-uninfected to
infected status was rapid, with no evidence of a prolonged period of intermittent
low-level viremia.
PMID- 28424254
TI - European Multicenter Study on Analytical Performance of Veris HIV-1 Assay.
AB - The analytical performance of the Veris HIV-1 assay for use on the new, fully
automated Beckman Coulter DxN Veris molecular diagnostics system was evaluated at
10 European virology laboratories. The precision, analytical sensitivity,
performance with negative samples, linearity, and performance with HIV-1
groups/subtypes were evaluated. The precision for the 1-ml assay showed a
standard deviation (SD) of 0.14 log10 copies/ml or less and a coefficient of
variation (CV) of <=6.1% for each level tested. The 0.175-ml assay showed an SD
of 0.17 log10 copies/ml or less and a CV of <=5.2% for each level tested. The
analytical sensitivities determined by probit analysis were 19.3 copies/ml for
the 1-ml assay and 126 copies/ml for the 0.175-ml assay. The performance with
1,357 negative samples demonstrated 99.2% with not detected results. Linearity
using patient samples was shown from 1.54 to 6.93 log10 copies/ml. The assay
performed well, detecting and showing linearity with all HIV-1 genotypes tested.
The Veris HIV-1 assay demonstrated analytical performance comparable to that of
currently marketed HIV-1 assays. (DxN Veris products are Conformite Europeenne
[CE]-marked in vitro diagnostic products. The DxN Veris product line has not been
submitted to the U.S. FDA and is not available in the U.S. market. The DxN Veris
molecular diagnostics system is also known as the Veris MDx molecular diagnostics
system and the Veris MDx system.).
PMID- 28424255
TI - Analysis of Milk from Mothers Who Delivered Prematurely Reveals Few Changes in
Proteases and Protease Inhibitors across Gestational Age at Birth and Infant
Postnatal Age.
AB - Background: Peptidomics research has demonstrated that protease activity is
higher in breast milk from preterm-delivering mothers than from term-delivering
mothers. However, to our knowledge, the effect of the degree of prematurity and
postnatal age on proteases and protease inhibitors in human milk remains
unknown.Objective: We aimed to determine the change of proteases and protease
inhibitors in milk from mothers who delivered prematurely across gestational age
(GA) and postnatal age.Methods: Milk samples were collected from 18 mothers aged
26-40 y who delivered preterm infants and who lacked mastitis. For analysis,
samples were separated into 2 groups: 9 from early GA (EGA) (24-26 wk GA)
delivering mothers and 9 from late GA (LGA) (27-32 wk GA)-delivering mothers.
Within the 9 samples in each group, the collection time ranged from postnatal
days 2 to 47. The activity and predicted activity of proteases in preterm milk
were determined with the use of fluorometric and spectrophotometric assays and
peptidomics, respectively. Protease and protease inhibitor concentrations were
determined with the use of ELISA. Linear mixed models were applied to compare
enzymes across GA and postnatal age.Results: Carboxypeptidase B2, kallikrein,
plasmin, elastase, thrombin, and cytosol aminopeptidase were present and active
in the milk of preterm-delivering mothers. Most milk protease and antiprotease
concentrations did not change with GA or postnatal age. However, the
concentration and activity of kallikrein, the most abundant and active protease
in preterm milk, increased by 25.4 ng . mL-1 . d-1 and 0.454 MUg . mL-1 . d-1
postnatally, respectively, in EGA milk samples while remaining stable in LGA milk
samples.Conclusions: This research demonstrates that proteases are active in
human milk and begin to degrade milk protein within the mammary gland before
consumption by infants. Proteases and protease inhibitors in milk from mothers of
premature infants mostly did not vary substantially across GA and postnatal age.
PMID- 28424256
TI - Dietary Patterns and Type 2 Diabetes: A Systematic Literature Review and Meta
Analysis of Prospective Studies.
AB - Background: Different methodologic approaches for constructing dietary patterns
and differences in their composition limit conclusions on healthful patterns for
diabetes prevention.Objective: We summarized evidence from prospective studies
that examined associations of dietary patterns with type 2 diabetes by
considering different methodologic approaches.Methods: The literature search
(MEDLINE and Web of Science) identified prospective studies (cohorts or trials)
that associated dietary patterns with diabetes incidence in nondiabetic and
apparently healthy participants. We summarized evidence by meta-analyses and
distinguished different methodologic approaches.Results: The search resulted in
48 articles comprising 16 cohorts. Adherence to the Mediterranean diet (RR for
comparing extreme quantiles: 0.87; 95% CI: 0.82, 0.93), Dietary Approaches to
Stop Hypertension (DASH) (RR: 0.81; 95% CI: 0.72, 0.92), and Alternative Healthy
Eating Index (AHEI) (RR: 0.79; 95% CI: 0.69, 0.90) was associated with
significant risk reductions of incident diabetes. Patterns from exploratory
factor and principal component analyses characterized by red and processed meat,
refined grains, high-fat dairy, eggs, and fried products ("mainly unhealthy")
were positively associated with diabetes (RR: 1.44; 95% CI: 1.27, 1.62), whereas
patterns characterized by vegetables, legumes, fruits, poultry, and fish ("mainly
healthy") were inversely associated with diabetes (RR: 0.84; 95% CI: 0.77, 0.91).
Reduced rank regression (RRR) used diabetes-related biomarkers to identify
patterns. These patterns were characterized by high intakes of refined grains,
sugar-sweetened soft drinks, and processed meat and were all significantly
associated with diabetes risk.Conclusions: Our meta-analysis suggests that diets
according to the Mediterranean diet, DASH, and AHEI have a strong potential for
preventing diabetes, although they differ in some particular components.
Exploratory dietary patterns were grouped based on concordant food groups and
were significantly associated with diabetes risk despite single-component foods
having limited evidence for an association. Still, they remain population
specific observations. Consistent positive associations with diabetes risk were
observed for 3 RRR patterns.
PMID- 28424257
TI - An Animal-Source Food Supplement Increases Micronutrient Intakes and Iron Status
among Reproductive-Age Women in Rural Vietnam.
AB - Background: Few studies have examined the impact of local animal-source foods
(ASFs) on the nutritional status of reproductive-age women in developing
countries.Objective: We hypothesized that a midmorning snack of local ASF for 6
mo would reduce dietary micronutrient deficiencies [usual intake less than the
estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc,
and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural
Vietnam.Methods: One hundred seventeen women, 18-30 y old, were randomly assigned
to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 MUg retinoic
acid equivalent vitamin A, and 5.5 MUg vitamin B-12) or a control snack (mean:
150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 MUg retinoic acid equivalent vitamin A, and 0
MUg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by
repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and
6 mo. Because of the relation between nutritional status and inflammation, serum
C-reactive protein, alpha-1-acid-glycoprotein, and urinary tract infections
(UTIs) were also monitored.Results: Eighty-nine women (47 in the ASF group and 42
controls) completed the study. In the ASF group, intakes of iron and vitamins A
and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake
was reduced to 9.6% compared with 64.7% in controls (P < 0.001). At 6 mo, a
modest increase (P < 0.05) in hemoglobin and iron status occurred in the ASF
group compared with the control group, but plasma zinc, retinol, and serum
vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 (P < 0.05)
among women assigned to the ASF group who had a low whole-body iron status at
baseline.Conclusions: Adding a small amount of locally produced ASF to the diets
of reproductive-age Vietnamese women improved micronutrient intakes and iron
status. However, the increased UTI incidence in women in the ASF group with
initially lower iron stores warrants further investigation.
PMID- 28424258
TI - Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron
Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia.
AB - Background: Antenatal anemia is a risk factor for adverse maternal and fetal
outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal
anemia is considered responsive to iron; identifying women in need of iron may
help target interventions. Iron absorption is governed by the iron-regulatory
hormone hepcidin.Objective: We sought to characterize changes in hepcidin and its
associations with indexes of iron stores, erythropoiesis, and inflammation at
weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential
as an index of iron deficiency.Methods: We measured hemoglobin and serum
hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein
(CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women
recruited to a randomized controlled trial. Associations with hepcidin were
measured by using linear regression, and hepcidin's diagnostic test accuracy
[area under the receiver operating characteristic curve (AUCROC), sensitivity,
specificity, cutoffs] for iron deficiency at each time point was
analyzed.Results: The prevalence of anemia increased from 34.6% at 14 wk of
gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study
enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of
gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP
declined over pregnancy. The AUCROC values for hepcidin to detect iron deficiency
(defined as ferritin <15 MUg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk,
respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of
iron deficiency.Conclusions: In Gambian pregnant women, hepcidin appears to be a
useful diagnostic test for iron deficiency and may enable the identification of
cases for whom iron would be beneficial. Hepcidin suppression in the second
trimester suggests a window for optimal timing for antenatal iron interventions.
Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial
was registered at www.isrctn.com as ISRCTN49285450.
PMID- 28424259
TI - Maternal Vitamin D Insufficiency Early in Pregnancy Is Associated with Increased
Risk of Preterm Birth in Ethnic Minority Women in Canada.
AB - Background: Maternal vitamin D insufficiency (plasma 25-hydroxyvitamin D
[25(OH)D] <75 nmol/L) may play a role in ethnic disparities in rates of preterm
and spontaneous preterm births.Objective: We explored the relation between
maternal plasma 25(OH)D concentration in the first trimester (8-14 wk of
gestation) and the risk of preterm and spontaneous preterm births (<37 wk of
gestation) by ethnicity.Methods: We designed a case-control study that included
120 cases of preterm birth (<37 wk of gestation) and 360 term controls (>=37 wk
of gestation) of singleton pregnancies from the 3D cohort, a multicenter study in
2456 pregnant women in Quebec, Canada. Plasma 25(OH)D was measured by LC-mass
spectrometry. We compared the distribution of vitamin D status between cases and
controls for 8 ethnic minority subgroups. We explored the association between
maternal plasma 25(OH)D concentration and preterm and spontaneous preterm births
with the use of splines in logistic regression by ethnicity.Results: The
distributions of maternal vitamin D status (<50, 50-75, and >75 nmol/L) were
different in preterm and spontaneous preterm birth cases compared with controls
but only in women of ethnic minority (P-trend = 0.003 and 0.024, respectively).
Among ethnic subgroups, sub-Saharan Africans (P-trend = 0.030) and Arab-West
Asians (P-trend = 0.045) showed an inverse relation between maternal vitamin D
status and the risk of preterm birth. Maternal plasma 25(OH)D concentrations of
30 nmol/L were associated with 4.05 times the risk of preterm birth in the total
ethnic minority population (95% CI: 1.16, 14.12; P = 0.028) relative to
participants with a concentration of 75 nmol/L. In contrast, there was no such
association among nonethnic women (OR: 0.94; 95% CI: 0.48, 1.82; P = 0.85). There
was no association when we considered only spontaneous preterm births in the
total ethnic minority population (OR: 1.75; 95% CI: 0.39, 7.79; P =
0.46).Conclusion: Vitamin D insufficiency is associated with an increased risk of
preterm birth in ethnic minority women in Canada.
PMID- 28424260
TI - Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for
Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and
Early Lactation.
AB - Background: Estimated physiologic requirements (PRs) for zinc increase in late
pregnancy and early lactation, but the effect on dietary zinc requirements is
uncertain.Objective: The aim of this study was to determine changes in daily
fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of
differing phytate contents in relation to physiologic zinc requirements during
pregnancy and lactation.Methods: This was a prospective observational study of
zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3)
and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of
childbearing age whose major food staple was maize and who had been randomly
assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate
maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary
zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined
from duplicate diets and fractional absorption (FAZ) by dual isotope ratio
technique (TAZ = TDZ * FAZ). All variables were examined longitudinally and by
group and compared with PRs. TAZ values at later phases were compared with phase
1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating
(NPNL) women.Results: TAZ was greater in the LP group than in the C group at all
phases. All variables increased from phase 1 to phases 2 and 3 and declined at
phase 4. TAZ increased by 1.25 mg/d (P = 0.045) in the C group and by 0.81 mg/d
(P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d
(P = 0.002) in the C group and 2.28 mg/d (P = 0.0004) in the LP group, compared
with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values
in phases 2-4.Conclusions: Upregulation of zinc absorption in late pregnancy and
early lactation matches increases in PRs of pregnant and lactating women,
regardless of dietary phytate, which has implications for dietary zinc
requirements of pregnant and lactating women.
PMID- 28424261
TI - Zinc Absorption from Milk Is Affected by Dilution but Not by Thermal Processing,
and Milk Enhances Absorption of Zinc from High-Phytate Rice in Young Dutch Women.
AB - Background: Milk has been suggested to increase zinc absorption. The effect of
processing and the ability of milk to enhance zinc absorption from other foods
has not been measured directly in humans.Objective: We aimed to assess zinc
absorption from 1) milk undergoing various processing and preparatory steps and
2) from intrinsically labeled high-phytate rice consumed with milk or
water.Methods: Two randomized crossover studies were conducted in healthy young
women [age:18-25 y; body mass index (in kg/m2): 20-25]: 1) a milk study (n = 19)
comparing the consumption of 800 mL full-fat ultra-high temperature (UHT) milk
[heat-treated milk (HTM)], full-fat UHT milk diluted 1:1 with water [heat-treated
milk and water (MW)], water, or unprocessed (raw) milk (UM), each extrinsically
labeled with 67Zn, and 2) a rice study (n = 18) comparing the consumption of 90 g
intrinsically 67Zn-labeled rice with 600 mL of water [rice and water (RW)] or
full-fat UHT milk [rice and milk (RM)]. The fractional absorption of zinc (FAZ)
was measured with the double-isotope tracer ratio method. In vitro, we assessed
zinc extraction from rice blended into water, UM, or HTM with or without
phytate.Results: FAZ from HTM was 25.5% (95% CI: 21.6%, 29.4%) and was not
different from UM (27.8%; 95% CI: 24.2%, 31.4%). FAZ from water was higher
(72.3%; 95% CI: 68.7%, 75.9%), whereas FAZ from MW was lower (19.7%; 95% CI:
17.5%, 21.9%) than HTM and UM (both P < 0.01). FAZ from RM (20.7%; 95% CI: 18.8%,
22.7%) was significantly higher than from RW (12.8%; 95% CI: 10.8%, 14.6%; P <
0.01). In vitro, HTM and UM showed several orders of magnitude higher extraction
of zinc from rice with HTM than from rice with water at various phytate
concentrations.Conclusions: Milk enhanced human FAZ from high-phytate rice by 62%
compared with water. Diluting milk with water decreases its absorption-enhancing
proprieties, whereas UHT processing does not. This trial was registered at the
Dutch trial registry as NTR4267
(http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4267).
PMID- 28424262
TI - Magnesium Reduces Hepatic Lipid Accumulation in Yellow Catfish (Pelteobagrus
fulvidraco) and Modulates Lipogenesis and Lipolysis via PPARA, JAK-STAT, and AMPK
Pathways in Hepatocytes.
AB - Background: Magnesium influences hepatic lipid deposition in vertebrates, but the
underlying mechanism is unknown.Objective: We used yellow catfish and their
isolated hepatocytes to test the hypothesis that magnesium influences lipid
deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow
catfish (mean +/- SEM weight: 3.43 +/- 0.02 g, 3 mo old, mixed sex) were fed a
0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary
hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or
without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C). Growth
performance, cell viability, triglyceride (TG) concentrations, and expression of
enzymes and genes involved in lipid metabolism were measured. Results: Compared
with fish fed low magnesium, those fed intermediate or high magnesium had lower
hepatic lipids (18%, 22%) and 6-phosphogluconate dehydrogenase (6PGD; 3.7%, 3.8%)
and malic enzyme (ME; 35%, 48%) activities and greater mRNA levels of the
lipolytic genes adipose triacylglyceride lipase (atgl; 82% and 1.7-fold) and
peroxisome proliferator-activated receptor (ppara; 18% and 1.0-fold),
respectively (P < 0.05). Relative mRNA levels of AMP-activated protein kinase
(ampk) a1, ampka2, ampkb1, ampkb2, ampkg1a, ampkg1b, Janus kinase (jak) 2a,
jak2b, and signal transducers and activators of transcription (stat) 3 in fish
fed high magnesium were higher (24% to 3.1-fold, P < 0.05) than in those fed low
or intermediate magnesium. Compared with cells incubated with MgSO4 alone, those
incubated with MgSO4 and pretreated with AG490, GW6471, or Compound C had greater
TG concentrations (42%, 31%, or 56%), g6pd (98%, 59%, or 51%), 6pgd (68%, 73%, or
32%) mRNA expression, and activities of G6PD (35%, 45%, or 16%) and ME (1.5-fold,
1.3-fold, or 13%), and reduced upregulation (61%, 25%, or 45%) of the lipolytic
gene, atgl (P < 0.05).Conclusions: Magnesium reduced hepatic lipid accumulation
in yellow catfish and the variation might be attributed to inhibited lipogenesis
and increased lipolysis. PPARA, JAK-STAT, and AMPK pathways mediated the
magnesium-induced changes in lipid deposition and metabolism. These results offer
new insight into magnesium nutrition in vertebrates.
PMID- 28424263
TI - The kielin/chordin-like protein (KCP) attenuates high-fat diet-induced obesity
and metabolic syndrome in mice.
AB - Obesity and its associated complications such as insulin resistance and non
alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF
beta superfamily is implicated in the regulation of white and brown adipose
tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted
regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and
activin signals while enhancing bone morphogenetic protein (BMP) signaling.
However, KCP's effects on metabolism and obesity have not been studied in animal
models. Therefore, we examined the effects of KCP loss or gain of function in
mice that were maintained on either a regular or a high-fat diet. KCP loss
sensitized the mice to obesity and associated complications such as glucose
intolerance and adipose tissue inflammation and fibrosis. In contrast, transgenic
mice that expressed KCP in the kidney, liver, and adipose tissues were resistant
to developing high-fat diet-induced obesity and had significantly reduced white
adipose tissue. Moreover, KCP overexpression shifted the pattern of SMAD
signaling in vivo, increasing the levels of phospho (P)-SMAD1 and decreasing P
SMAD3. Adipocytes in culture showed a cell-autonomous effect in response to added
TGF-beta1 or BMP7. Metabolic profiling indicated increased energy expenditure in
KCP-overexpressing mice and reduced expenditure in the KCP mutants with no effect
on food intake or activity. These findings demonstrate that shifting the TGF-beta
superfamily signaling with a secreted protein can alter the physiology and
thermogenic properties of adipose tissue to reduce obesity even when mice are fed
a high-fat diet.
PMID- 28424264
TI - Identification of a multienzyme complex for glucose metabolism in living cells.
AB - Sequential metabolic enzymes in glucose metabolism have long been hypothesized to
form multienzyme complexes that regulate glucose flux in living cells. However,
it has been challenging to directly observe these complexes and their functional
roles in living systems. In this work, we have used wide-field and confocal
fluorescence microscopy to investigate the spatial organization of metabolic
enzymes participating in glucose metabolism in human cells. We provide compelling
evidence that human liver-type phosphofructokinase 1 (PFKL), which catalyzes a
bottleneck step of glycolysis, forms various sizes of cytoplasmic clusters in
human cancer cells, independent of protein expression levels and of the choice of
fluorescent tags. We also report that these PFKL clusters colocalize with other
rate-limiting enzymes in both glycolysis and gluconeogenesis, supporting the
formation of multienzyme complexes. Subsequent biophysical characterizations with
fluorescence recovery after photobleaching and FRET corroborate the formation of
multienzyme metabolic complexes in living cells, which appears to be controlled
by post-translational acetylation on PFKL. Importantly, quantitative high-content
imaging assays indicated that the direction of glucose flux between glycolysis,
the pentose phosphate pathway, and serine biosynthesis seems to be spatially
regulated by the multienzyme complexes in a cluster-size-dependent manner.
Collectively, our results reveal a functionally relevant, multienzyme metabolic
complex for glucose metabolism in living human cells.
PMID- 28424265
TI - Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell
surface interactions.
AB - GNE (UDP-GlcNAc 2-epimerase/ManNAc kinase) myopathy is a rare muscle disorder
associated with aging and is related to sporadic inclusion body myositis, the
most common acquired muscle disease of aging. Although the cause of sporadic
inclusion body myositis is unknown, GNE myopathy is associated with mutations in
GNE. GNE harbors two enzymatic activities required for biosynthesis of sialic
acid in mammalian cells. Mutations to both GNE domains are linked to GNE
myopathy. However, correlation between mutation-associated reductions in sialic
acid production and disease severity is imperfect. To investigate other potential
effects of GNE mutations, we compared sialic acid production in cell lines
expressing wild type or mutant forms of GNE. Although we did not detect any
differences attributable to disease-associated mutations, lectin binding and mass
spectrometry analysis revealed that GNE deficiency is associated with
unanticipated effects on the structure of cell-surface glycans. In addition to
exhibiting low levels of sialylation, GNE-deficient cells produced distinct N
linked glycan structures with increased branching and extended poly-N
acetyllactosamine. GNE deficiency may affect levels of UDP-GlcNAc, a key
metabolite in the nutrient-sensing hexosamine biosynthetic pathway, but this
modest effect did not fully account for the change in N-linked glycan structure.
Furthermore, GNE deficiency and glucose supplementation acted independently and
additively to increase N-linked glycan branching. Notably, N-linked glycans
produced by GNE-deficient cells displayed enhanced binding to galectin-1,
indicating that changes in GNE activity can alter affinity of cell-surface
glycoproteins for the galectin lattice. These findings suggest an unanticipated
mechanism by which GNE activity might affect signaling through cell-surface
receptors.
PMID- 28424266
TI - Disease-associated extracellular loop mutations in the adhesion G protein-coupled
receptor G1 (ADGRG1; GPR56) differentially regulate downstream signaling.
AB - Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as
GPR56) underlie the neurological disorder bilateral frontoparietal
polymicrogyria. Disease-associated mutations in G1 studied to date are believed
to induce complete loss of receptor function through disruption of either
receptor trafficking or signaling activity. Given that N-terminal truncation of
G1 and other adhesion G protein-coupled receptors has been shown to significantly
increase the receptors' constitutive signaling, we examined two different
bilateral frontoparietal polymicrogyria-inducing extracellular loop mutations
(R565W and L640R) in the context of both full-length and N-terminally truncated
(DeltaNT) G1. Interestingly, we found that these mutations reduced surface
expression of full-length G1 but not G1-DeltaNT in HEK-293 cells. Moreover, the
mutations ablated receptor-mediated activation of serum response factor
luciferase, a classic measure of Galpha12/13-mediated signaling, but had no
effect on G1-mediated signaling to nuclear factor of activated T cells (NFAT)
luciferase. Given these differential signaling results, we sought to further
elucidate the pathway by which G1 can activate NFAT luciferase. We found no
evidence that DeltaNT activation of NFAT is dependent on Galphaq/11-mediated or
beta-arrestin-mediated signaling but rather involves liberation of Gbetagamma
subunits and activation of calcium channels. These findings reveal that disease
associated mutations to the extracellular loops of G1 differentially alter
receptor trafficking, depending on the presence of the N terminus, and
differentially alter signaling to distinct downstream pathways.
PMID- 28424267
TI - Using a novel data resource to explore heart rate during mountain and road
running.
AB - Online, accessible performance and heart rate data from running competitions are
posted publicly or semi-publicly to social media. We tested the efficacy of one
such data resource- Strava- as a tool in exercise physiology investigations by
exploring heart rate differences in mountain racing and road racing running
events. Heart rate and GPS pace data were gathered from Strava activities posted
by 111 males aged 21-49, from two mountain races (Mt. Washington Road Race and
Pike's Peak Ascent) and two road race distances (half marathon and marathon).
Variables of interest included race finish time, average heart rate, time to
complete the first half (by distance) of the race, time to complete the second
half, average heart rate for both the first and second half, estimated maximal
heart rate, and competitiveness (finish time as percentage of winning time).
Mountain runners on average showed no change in heart rate in the second versus
first half of the event, while road racers at the half marathon and marathon
distances showed increased second-half heart rate. Mountain runners slowed
considerably more in the second half than road runners. Heart rate increases in
road races were likely reflective of cardiac drift. Altitude and other demands
specific to mountain racing may explain why this was not observed in mountain
races. Strava presents enormous untapped opportunity for exercise physiology
research, enabling initial inquiry into physiological questions that may then be
followed by targeted laboratory studies.
PMID- 28424268
TI - Favorable outcome in patients with intracranial hemorrhage due to ruptured brain
AVM.
PMID- 28424269
TI - Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course
analysis of CHANCE.
AB - OBJECTIVE: To investigate the short-term time course risks and benefits of
clopidogrel with aspirin in minor ischemic stroke or TIA. METHODS: Data were
derived from the Clopidogrel in High-Risk Patients with Acute Nondisabling
Cerebrovascular Events (CHANCE) trial. The primary outcome was a new ischemic
stroke. Safety outcomes included any bleeding and moderate to severe bleeding.
Time course analyses were performed for the outcomes of both stroke and bleeding.
RESULTS: A total of 145 (71.1%), 13 (6.4%), and 12 (5.9%) of 204 new ischemic
strokes in the clopidogrel-aspirin group vs 223 (75.6%), 19 (6.4%), and 8 (2.7%)
of 295 in the aspirin alone group occurred at the first, second, and third week,
respectively. A total of 23 (38.3%), 15 (25.0%), and 9 (15.0%) of 60 bleeding
cases in the clopidogrel-aspirin group vs 15 (36.6%), 8 (19.5%), and 3 (7.3%) of
41 in the aspirin alone group occurred at the first, second, and third week,
respectively. Clopidogrel-aspirin treatment numerically reduced the risk of
ischemic stroke within the first 2 weeks. From the 10th day, the number of any
bleeding cases caused by dual antiplatelets outweighed that of new stroke reduced
by dual antiplatelets. CONCLUSIONS: Clopidogrel-aspirin treatment may have a
benefit of reducing stroke risk outweighing the potential risk of increased
bleeding especially within the first 2 weeks compared with aspirin alone in
patients with minor stroke or TIA. CLINICALTRIALSGOV IDENTIFIER: NCT00979589.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for
patients with minor stroke or TIA, the reduction of stroke risk from clopidogrel
plus aspirin within the first 2 weeks outweighs the risk of bleeding compared
with aspirin alone.
PMID- 28424271
TI - Nrf2, cellular redox regulation, and neurologic implications.
PMID- 28424270
TI - Significance of circadian rhythms in severely brain-injured patients: A clue to
consciousness?
AB - OBJECTIVE: To investigate the relationship between the presence of a circadian
body temperature rhythm and behaviorally assessed consciousness levels in
patients with disorders of consciousness (DOC; i.e., vegetative
state/unresponsive wakefulness syndrome or minimally conscious state). METHODS:
In a cross-sectional study, we investigated the presence of circadian temperature
rhythms across 6 to 7 days using external skin temperature sensors in 18 patients
with DOC. Beyond this, we examined the relationship between behaviorally assessed
consciousness levels and circadian rhythmicity. RESULTS: Analyses with Lomb
Scargle periodograms revealed significant circadian rhythmicity in all patients
(range 23.5-26.3 hours). We found that especially scores on the arousal subscale
of the Coma Recovery Scale-Revised were closely linked to the integrity of
circadian variations in body temperature. Finally, we piloted whether bright
light stimulation could boost circadian rhythmicity and found positive evidence
in 2 out of 8 patients. CONCLUSION: The study provides evidence for an
association between circadian body temperature rhythms and arousal as a necessary
precondition for consciousness. Our findings also make a case for circadian
rhythms as a target for treatment as well as the application of diagnostic and
therapeutic means at times when cognitive performance is expected to peak.
PMID- 28424272
TI - Trends in dementia prevalence, incidence, and survival rate in a Japanese
community.
AB - OBJECTIVE: To investigate secular trends in the prevalence, incidence, and
survival rate of dementia in a Japanese elderly population in a comprehensive
manner. METHODS: Five cross-sectional surveys of dementia were conducted among
residents of a Japanese community, aged >=65 years, in 1985, 1992, 1998, 2005,
and 2012. We also established 2 cohorts consisting of the residents of this age
group without dementia in 1988 (n = 803) and 2002 (n = 1,231), and each was
followed for 10 years. RESULTS: The age-standardized prevalence of all-cause
dementia and Alzheimer disease (AD) increased with time (for all-cause dementia:
6.8% in 1985, 4.6% in 1992, 5.3% in 1998, 8.4% in 2005, and 11.3% in 2012, p for
trend <0.01; for AD: 1.5%, 1.4%, 2.4%, 3.9%, and 7.2%, respectively, p for trend
<0.01), while no secular change was observed for vascular dementia (VaD) (2.4%,
1.6%, 1.5%, 2.4%, and 2.4%, respectively, p for trend = 0.59). The age- and sex
adjusted incidence of all-cause dementia and AD, but not VaD, increased from the
1988 cohort to the 2002 cohort (for all-cause dementia: adjusted hazard ratio
[aHR] 1.68, 95% confidence interval [CI] 1.38-2.06; for AD: aHR 2.07, 95% CI 1.59
2.70; for VaD: aHR 1.18, 95% CI 0.83-1.69). The 5-year survival rate of all-cause
dementia and AD improved from the 1988 cohort to the 2002 cohort (for all-cause
dementia: 47.3% to 65.2%; for AD: 50.7% to 75.1%; all p < 0.01). CONCLUSIONS: The
increased incidence and improved survival rate of AD could have resulted in the
steep increase in AD prevalence in the Japanese elderly.
PMID- 28424273
TI - Certainty of genuine treatment increases drug responses among intellectually
disabled patients.
AB - OBJECTIVE: To determine the placebo component of treatment responses in patients
with intellectual disability (ID). METHODS: A statistical meta-analysis comparing
bias-corrected effect sizes (Hedges g) of drug responses in open-label vs placebo
controlled clinical trials was performed, as these trial types represent
different certainty of receiving genuine treatment (100% vs 50%). Studies in
fragile X, Down, Prader-Willi, and Williams syndrome published before June 2015
were considered. RESULTS: Seventeen open-label trials (n = 261, 65% male; mean
age 23.6 years; mean trial duration 38 weeks) and 22 placebo-controlled trials (n
= 721, 62% male; mean age 17.1 years; mean trial duration 35 weeks) were
included. The overall effect size from pre to post treatment in open-label
studies was g = 0.602 (p = 0.001). The effect of trial type was statistically
significant (p = 0.001), and revealed higher effect sizes in studies with 100%
likelihood of getting active drug, compared to both the drug and placebo arm of
placebo-controlled trials. We thus provide evidence for genuine placebo effects,
not explainable by natural history or regression toward the mean, among patients
with ID. CONCLUSIONS: Our data suggest that clinical trials in patients with
severe cognitive deficits are influenced by the certainty of receiving genuine
medication, and open-label design should thus not be used to evaluate the effect
of pharmacologic treatments in ID, as the results will be biased by an enhanced
placebo component.
PMID- 28424274
TI - Copeptin and NT-proBNP for prediction of all-cause and cardiovascular death in
ischemic stroke.
AB - OBJECTIVE: To evaluate long-term mortality in patients with acute ischemic stroke
(AIS) by exploring the correlation between death and plasma concentrations of
copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a cohort
study. METHODS: In a prospective, multicenter observational study of 4,215
patients with AIS, copeptin and NT-proBNP levels were measured with a
standardized method when patients were admitted to hospital. The primary endpoint
was all-cause mortality or cardiovascular disease (CVD) mortality within 1 year.
RESULTS: During a follow-up period, 906 patients (20.1%, 95% confidence interval
[CI] 18.9-21.2) died, including 589 cases of CVD mortality (13.1%, 95% CI 12.1
14.0). With the use of a multivariate analysis, both markers were found to have
prognostic value in the same model (CVD mortality: odds ratio [OR] for fourth
quartile of copeptin and NT-proBNP 1.68 and 2.58, 95% CI 1.22-2.49 and 1.76-4.05,
respectively; all-cause mortality: OR for fourth quartile of copeptin and NT
proBNP 1.48 and 2.47, 95% CI 1.22-2.03 and 1.68-3.95, respectively). In a
receiver operating characteristics analysis of CVD mortality, the area under the
curve varied from 0.80 to 0.83 (95% CI 0.79-0.87) when the index of NT-proBNP was
added and increased to 0.86 (95% CI 0.83-0.90) when both markers were added.
CONCLUSIONS: Copeptin and NT-proBNP may be useful independent prognostic markers
of all-cause or CVD mortality in Chinese patients with AIS.
PMID- 28424275
TI - Outcomes after intracerebral hemorrhage from arteriovenous malformations.
AB - OBJECTIVE: To compare outcomes after intracerebral hemorrhage (ICH) from cerebral
arteriovenous malformation (AVM) rupture and other causes of ICH. METHODS: We
performed a retrospective population-based study using data from the Nationwide
Inpatient Sample. We used standard diagnosis codes to identify ICH cases from
2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were
inpatient mortality and home discharge. We used logistic regression to compare
outcomes between patients with ICH with and without AVM while adjusting for
demographics, comorbidities, and hospital characteristics. In a confirmatory
analysis using a prospective cohort of patients hospitalized with ICH at our
institution, we additionally adjusted for hematoma characteristics and the
Glasgow Coma Scale score. RESULTS: Among 619,167 ICH hospitalizations, the 4,485
patients (0.7%, 95% confidence interval [CI] 0.6-0.8) with an AVM were younger
and had fewer medical comorbidities than patients without AVM. After adjustment
for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5,
95% CI 0.4-0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4-3.0) than
patients without AVM. In a confirmatory analysis of 342 patients with ICH at our
institution, the 34 patients (9.9%, 95% CI 7.2-13.6) with a ruptured AVM had
higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4-13.1)
compared to patients without AVM. CONCLUSIONS: Patients with ICH due to ruptured
AVM have more favorable outcomes than patients with ICH from other causes.
PMID- 28424276
TI - Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor Dependent.
AB - Nephrotic syndrome is characterized by massive proteinuria and injury of
specialized glomerular epithelial cells called podocytes. Studies have shown
that, whereas low-concentration thrombin may be cytoprotective, higher thrombin
concentrations may contribute to podocyte injury. We and others have demonstrated
that ex vivo plasma thrombin generation is enhanced during nephrosis, suggesting
that thrombin may contribute to nephrotic progression. Moreover, nonspecific
thrombin inhibition has been shown to decrease proteinuria in nephrotic animal
models. We thus hypothesized that thrombin contributes to podocyte injury in a
protease-activated receptor-specific manner during nephrosis. Here, we show that
specific inhibition of thrombin with hirudin reduced proteinuria in two rat
nephrosis models, and thrombin colocalized with a podocyte-specific marker in rat
glomeruli. Furthermore, flow cytometry immunophenotyping revealed that rat
podocytes express the protease-activated receptor family of coagulation receptors
in vivo High-concentration thrombin directly injured conditionally immortalized
human and rat podocytes. Using receptor-blocking antibodies and activation
peptides, we determined that thrombin-mediated injury depended upon interactions
between protease-activated receptor 3 and protease-activated receptor 4 in human
podocytes, and between protease-activated receptor 1 and protease-activated
receptor 4 in rat podocytes. Proximity ligation and coimmunoprecipitation assays
confirmed thrombin-dependent interactions between human protease-activated
receptor 3 and protease-activated receptor 4, and between rat protease-activated
receptor 1 and protease-activated receptor 4 in cultured podocytes. Collectively,
these data implicate thrombinuria as a contributor to podocyte injury during
nephrosis, and suggest that thrombin and/or podocyte-expressed thrombin receptors
may be novel therapeutic targets for nephrotic syndrome.
PMID- 28424278
TI - Detection of HPV subtypes by mass spectrometry in FFPE tissue specimens: a
reliable tool for routine diagnostics.
AB - AIMS: Human papilloma virus (HPV) infection is a causative agent for
approximately 5% of all new cancer cases in humans. The virus is detected in
cervical, anal, vaginal, penile, vulvar and head and neck cancers and has
prognostic implications. Thus, test systems are required to detect high-risk but
also low-risk HPV subtypes with high specificity and sensitivity in a time
effective and cost-effective manner. In the present study we developed a new mass
spectrometry (MS)-based test system for the detection of HPV infections in
formalin-fixed paraffin-embedded (FFPE) tissue samples. METHODS: A high
throughput matrix-assisted laser desorption ionisation time of flight MS-based
assay was applied to genotype 19 HPV types in FFPE tissue specimens (n=46). The
results from the MS assay were compared with the results obtained from two
hybridisation-based test systems: the HPV 3.5 LCD-array kit and the EuroArrayHPV
system. RESULTS: In 36 out of 46 (78%) tissue samples, a HPV infection could be
detected by the MS-based HPV assay. In 16 samples (44%) only one and in 20
samples (56%) two to six HPV subtypes were identified. The overall agreement of
all three assays was almost perfect (Cohen's k value: 0.83). CONCLUSIONS: The MS
based assay is highly sensitive, reliable as well as cost-effective and
represents a suitable technology for the detection of HPV infections in FFPE
tissue material.
PMID- 28424277
TI - Janus Kinase 2 Regulates Transcription Factor EB Expression and Autophagy
Completion in Glomerular Podocytes.
AB - The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a
promising therapeutic target for the treatment of CKD. However, being
ubiquitously expressed in the adult, JAK2 is also likely to be necessary for
normal organ function. Here, we investigated the phenotypic effects of JAK2
deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an
elevation in urine albumin excretion that was accompanied by increased podocyte
autophagosome fractional volume and p62 aggregation, which are indicative of
impaired autophagy completion. In cultured podocytes, knockdown of JAK2 similarly
impaired autophagy and led to downregulation in the expression of lysosomal genes
and decreased activity of the lysosomal enzyme, cathepsin D. Because
transcription factor EB (TFEB) has recently emerged as a master regulator of
autophagosome-lysosome function, controlling the expression of several of the
genes downregulated by JAK2 knockdown, we questioned whether TFEB is regulated by
JAK2. In immortalized mouse podocytes, JAK2 knockdown decreased TFEB promoter
activity, expression, and nuclear localization. In silico analysis and chromatin
immunoprecipitation assays revealed that the downstream mediator of JAK2
signaling STAT1 binds to the TFEB promoter. Finally, overexpression of TFEB in
JAK2-deficient podocytes reversed lysosomal dysfunction and restored albumin
permselectivity. Collectively, these observations highlight the homeostatic
actions of JAK2 in podocytes and the importance of TFEB to autophagosome-lysosome
function in these cells. These results also raise the possibility that
therapeutically modulating TFEB activity may improve podocyte health in
glomerular disease.
PMID- 28424279
TI - Phosphorylation Induces Structural Changes in the Autographa californica
Nucleopolyhedrovirus P10 Protein.
AB - Baculoviruses encode a variety of auxiliary proteins that are not essential for
viral replication but provide them with a selective advantage in nature. P10 is a
10-kDa auxiliary protein produced in the very late phase of gene transcription by
Autographa californica multiple nucleopolyhedrovirus (AcMNPV). The P10 protein
forms cytoskeleton-like structures in the host cell that associate with
microtubules varying from filamentous forms in the cytoplasm to aggregated
perinuclear tubules that form a cage-like structure around the nucleus. These P10
structures may have a role in the release of occlusion bodies (OBs) and thus
mediate the horizontal transmission of the virus between insect hosts. Here,
using mass spectrometric analysis, it is demonstrated that the C terminus of P10
is phosphorylated during virus infection of cells in culture. Analysis of P10
mutants encoded by recombinant baculoviruses in which putative phosphorylation
residues were mutated to alanine showed that serine 93 is a site of
phosphorylation. Confocal microscopy examination of the serine 93 mutant
structures revealed aberrant formation of the perinuclear tubules. Thus, the
phosphorylation of serine 93 may induce the aggregation of filaments to form
tubules. Together, these data suggest that the phosphorylation of serine 93
affects the structural conformation of P10.IMPORTANCE The baculovirus P10 protein
has been researched intensively since it was first observed in 1969, but its role
during viral infection remains unclear. It is conserved in the alphabaculoviruses
and expressed at high levels during virus infection. Producing large amounts of a
protein is wasteful for the virus unless it is advantageous for the survival of
its progeny, and therefore, P10 presents an enigma. As P10 polymerizes to form
organized cytoskeletal structures that colocalize with host cell microtubules,
the structural relationship of the protein with the host cell may present a key
to help understand the function and importance of this protein. This study
addresses the importance of the structural changes in P10 during infection and
how they may be governed by phosphorylation. The P10 structures affected by
phosphorylation are closely associated with the viral progeny and thus may
potentially be responsible for its dissemination and survival.
PMID- 28424280
TI - The Major Envelope Glycoprotein of Murid Herpesvirus 4 Promotes Sexual
Transmission.
AB - Gammaherpesviruses are important human and animal pathogens. Infection control
has proven difficult because the key process of transmission is ill understood.
Murid herpesvirus 4 (MuHV-4), a gammaherpesvirus of mice, is transmitted
sexually. We show that this depends on the major virion envelope glycoprotein
gp150. gp150 is redundant for host entry, and in vitro, it regulates rather than
promotes cell binding. We show that gp150-deficient MuHV-4 reaches and replicates
normally in the female genital tract after nasal infection but is poorly released
from vaginal epithelial cells and fails to pass from the female to the male
genital tract during sexual contact. Thus, we show that the regulation of virion
binding is a key component of spontaneous gammaherpesvirus
transmission.IMPORTANCE Gammaherpesviruses are responsible for many important
diseases in both animals and humans. Some important aspects of their life cycle
are still poorly understood. Key among these is viral transmission. Here we show
that the major envelope glycoprotein of murid herpesvirus 4 functions not in
entry or dissemination but in virion release to allow sexual transmission to new
hosts.
PMID- 28424281
TI - Distinct Roles of Vaccinia Virus NF-kappaB Inhibitor Proteins A52, B15, and K7 in
the Immune Response.
AB - Poxviruses use a complex strategy to escape immune control, by expressing
immunomodulatory proteins that could limit their use as vaccine vectors. To test
the role of poxvirus NF-kappaB pathway inhibitors A52, B15, and K7 in immunity,
we deleted their genes in an NYVAC (New York vaccinia virus) strain that
expresses HIV-1 clade C antigens. After infection of mice, ablation of the A52R,
B15R, and K7R genes increased dendritic cell, natural killer cell, and neutrophil
migration as well as chemokine/cytokine expression. Revertant viruses with these
genes confirmed their role in inhibiting the innate immune system. To different
extents, enhanced innate immune responses correlated with increased HIV Pol- and
Gag-specific polyfunctional CD8 T cell and HIV Env-specific IgG responses induced
by single-, double-, and triple-deletion mutants. These poxvirus proteins thus
influence innate and adaptive cell-mediated and humoral immunity, and their
ablation offers alternatives for design of vaccine vectors that regulate immune
responses distinctly.IMPORTANCE Poxvirus vectors are used in clinical trials as
candidate vaccines for several pathogens, yet how these vectors influence the
immune system is unknown. We developed distinct poxvirus vectors that express
heterologous antigens but lack different inhibitors of the central host-cell
signaling pathway. Using mice, we studied the capacity of these viruses to induce
innate and adaptive immune responses and showed that these vectors can distinctly
regulate the magnitude and quality of these responses. These findings provide
important insights into the mechanism of poxvirus-induced immune response and
alternative strategies for vaccine vector design.
PMID- 28424282
TI - Formation of a Viral Replication Focus in Sulfolobus Cells Infected by the
Rudivirus Sulfolobus islandicus Rod-Shaped Virus 2.
AB - Viral factories are compartmentalized centers for viral replication and assembly
in infected eukaryotic cells. Here, we report the formation of a replication
focus by prototypical archaeal Sulfolobus islandicus rod-shaped virus 2 (SIRV2)
in the model archaeon Sulfolobus This rod-shaped virus belongs to the viral
family Rudiviridae, carrying linear double-stranded DNA (dsDNA) genomes, which
are very common in geothermal environments. We demonstrate that SIRV2 DNA
synthesis is confined to a focus near the periphery of infected cells. Moreover,
viral and cellular replication proteins are recruited to, and concentrated in,
the viral replication focus. Furthermore, we show that of the four host DNA
polymerases (DNA polymerase I [Dpo1] to Dpo4), only Dpo1 participates in viral
DNA synthesis. This constitutes the first report of the formation of a viral
replication focus in archaeal cells, suggesting that organization of viral
replication in foci is a widespread strategy employed by viruses of the three
domains of life.IMPORTANCE The organization of viral replication in foci or viral
factories has been mostly described for different eukaryotic viruses and for
several bacteriophages. This work constitutes the first report of the formation
of a viral replication center by a virus infecting members of the Archaea domain.
PMID- 28424283
TI - Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary
Lymphoid Organs Is Associated with Robust CXCL10 Expression in
Monocyte/Macrophage Subsets.
AB - Glycosylation of Env defines pathogenic properties of simian immunodeficiency
virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live
attenuated, quintuple deglycosylated Env mutant (Delta5G) virus target CD4+ T
cells residing in different tissues during acute infection. SIVmac239 and Delta5G
preferentially infected distinct CD4+ T cells in secondary lymphoid organs (SLOs)
and within the lamina propria of the small intestine, respectively (C. Sugimoto
et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here,
we studied the host responses relevant to SIV targeting of CXCR3+ CCR5+ CD4+ T
cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized
inflammatory responses, defined by expression of CXCR3 chemokines, were
distinctly induced in the SIVmac239-infected animals. Consistent with robust
expression of CXCL10, CXCR3+ T cells were depleted from blood in the SIVmac239
infected animals. We also discovered that elevation of CXCL10 expression in blood
and SLOs was secondary to the induction of CD14+ CD16+ monocytes and MAC387+
macrophages, respectively. Since the significantly higher levels of SIV infection
in SLOs occurred with a massive accumulation of infiltrated MAC387+ macrophages,
T cells, dendritic cells (DCs), and residential macrophages near high endothelial
venules, the results highlight critical roles of innate/inflammatory responses in
SIVmac239 infection. Restricted infection in SLOs by Delta5G also suggests that
glycosylation of Env modulates innate/inflammatory responses elicited by cells of
monocyte/macrophage/DC lineages.IMPORTANCE We previously demonstrated that a
pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Delta5G
virus infected distinct CD4+ T cell subsets in SLOs and the small intestine,
respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012,
https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239,
but not with Delta5G, deplete CXCR3+ CCR5+ CD4+ T (Th1) cells during the primary
infection, thereby compromising the cellular immune response. Thus, we
hypothesized that distinct host responses are elicited by the infections with two
different viruses. We found that SIVmac239 induced distinctly higher levels of
inflammatory Th1 responses than Delta5G. In particular, SIVmac239 infection
elicited robust expression of CXCL10, a chemokine for CXCR3+ cells, in CD14+
CD16+ monocytes and MAC387+ macrophages recently infiltrated in SLOs. In
contrast, Delta5G infection elicited only modest inflammatory responses. These
results suggest that the glycosylation of Env modulates the inflammatory/Th1
responses through the monocyte/macrophage subsets and elicits marked differences
in SIV infection and clinical outcomes.
PMID- 28424284
TI - A Novel Type of Polyhedral Viruses Infecting Hyperthermophilic Archaea.
AB - Encapsidation of genetic material into polyhedral particles is one of the most
common structural solutions employed by viruses infecting hosts in all three
domains of life. Here, we describe a new virus of hyperthermophilic archaea,
Sulfolobus polyhedral virus 1 (SPV1), which condenses its circular double
stranded DNA genome in a manner not previously observed for other known viruses.
The genome complexed with virion proteins is wound up sinusoidally into a
spherical coil which is surrounded by an envelope and further encased by an outer
polyhedral capsid apparently composed of the 20-kDa virion protein. Lipids
selectively acquired from the pool of host lipids are integral constituents of
the virion. None of the major virion proteins of SPV1 show similarity to
structural proteins of known viruses. However, minor structural proteins, which
are predicted to mediate host recognition, are shared with other
hyperthermophilic archaeal viruses infecting members of the order Sulfolobales
The SPV1 genome consists of 20,222 bp and contains 45 open reading frames, only
one-fifth of which could be functionally annotated.IMPORTANCE Viruses infecting
hyperthermophilic archaea display a remarkable morphological diversity, often
presenting architectural solutions not employed by known viruses of bacteria and
eukaryotes. Here we present the isolation and characterization of Sulfolobus
polyhedral virus 1, which condenses its genome into a unique spherical coil. Due
to the original genomic and architectural features of SPV1, the virus should be
considered a representative of a new viral family, "Portogloboviridae."
PMID- 28424285
TI - Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8+ T and
CD21+ B Lymphocytes but Not for Glandular Epithelium at the Primary Site of
Persistent Infection in the Stallion Reproductive Tract.
AB - Equine arteritis virus (EAV) has a global impact on the equine industry as the
causative agent of equine viral arteritis (EVA), a respiratory, systemic, and
reproductive disease of equids. A distinctive feature of EAV infection is that it
establishes long-term persistent infection in 10 to 70% of infected stallions
(carriers). In these stallions, EAV is detectable only in the reproductive tract,
and viral persistence occurs despite the presence of high serum neutralizing
antibody titers. Carrier stallions constitute the natural reservoir of the virus
as they continuously shed EAV in their semen. Although the accessory sex glands
have been implicated as the primary sites of EAV persistence, the viral host cell
tropism and whether viral replication in carrier stallions occurs in the presence
or absence of host inflammatory responses remain unknown. In this study, dual
immunohistochemical and immunofluorescence techniques were employed to
unequivocally demonstrate that the ampulla is the main EAV tissue reservoir
rather than immunologically privileged tissues (i.e., testes). Furthermore, we
demonstrate that EAV has specific tropism for stromal cells (fibrocytes and
possibly tissue macrophages) and CD8+ T and CD21+ B lymphocytes but not glandular
epithelium. Persistent EAV infection is associated with moderate, multifocal
lymphoplasmacytic ampullitis comprising clusters of B (CD21+) lymphocytes and
significant infiltration of T (CD3+, CD4+, CD8+, and CD25+) lymphocytes, tissue
macrophages, and dendritic cells (Iba-1+ and CD83+), with a small number of
tissue macrophages expressing CD163 and CD204 scavenger receptors. This study
suggests that EAV employs complex immune evasion mechanisms that warrant further
investigation.IMPORTANCE The major challenge for the worldwide control of EAV is
that this virus has the distinctive ability to establish persistent infection in
the stallion's reproductive tract as a mechanism to ensure its maintenance in
equid populations. Therefore, the precise identification of tissue and cellular
tropism of EAV is critical for understanding the molecular basis of viral
persistence and for development of improved prophylactic or treatment strategies.
This study significantly enhances our understanding of the EAV carrier state in
stallions by unequivocally identifying the ampullae as the primary sites of viral
persistence, combined with the fact that persistence involves continuous viral
replication in fibrocytes (possibly including tissue macrophages) and T and B
lymphocytes in the presence of detectable inflammatory responses, suggesting the
involvement of complex viral mechanisms of immune evasion. Therefore, EAV
persistence provides a powerful new natural animal model to study RNA virus
persistence in the male reproductive tract.
PMID- 28424286
TI - Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are
Consistent with Intersubtype Differences in HIV-1 Disease Progression.
AB - There are marked differences in the spread and prevalence of HIV-1 subtypes
worldwide, and differences in clinical progression have been reported. However,
the biological reasons underlying these differences are unknown. Gag-protease is
essential for HIV-1 replication, and Gag-protease-driven replication capacity has
previously been correlated with disease progression. We show that Gag-protease
replication capacity correlates significantly with that of whole isolates (r =
0.51; P = 0.04), indicating that Gag-protease is a significant contributor to
viral replication capacity. Furthermore, we investigated subtype-specific
differences in Gag-protease-driven replication capacity using large well
characterized cohorts in Africa and the Americas. Patient-derived Gag-protease
sequences were inserted into an HIV-1 NL4-3 backbone, and the replication
capacities of the resulting recombinant viruses were measured in an HIV-1
inducible reporter T cell line by flow cytometry. Recombinant viruses expressing
subtype C Gag-proteases exhibited substantially lower replication capacities than
those expressing subtype B Gag-proteases (P < 0.0001); this observation remained
consistent when representative Gag-protease sequences were engineered into an HIV
1 subtype C backbone. We identified Gag residues 483 and 484, located within the
Alix-binding motif involved in virus budding, as major contributors to subtype
specific replicative differences. In East African cohorts, we observed a
hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C < D <
intersubtype recombinants (P < 0.0029), which is consistent with reported
intersubtype differences in disease progression. We thus hypothesize that the
lower Gag-protease-driven replication capacity of subtypes A and C slows disease
progression in individuals infected with these subtypes, which in turn leads to
greater opportunity for transmission and thus increased prevalence of these
subtypes.IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there
are reported differences in their rates of disease progression and epidemic
spread. The biological determinants underlying these differences have not been
fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication
capacity correlates with the replication capacity of whole virus isolates. We
further show that subtype B displays a significantly higher Gag-protease-mediated
replication capacity than does subtype C, and we identify a major genetic
determinant of these differences. Moreover, in two independent East African
cohorts we demonstrate a reproducible hierarchy of Gag-protease-driven
replicative capacity, whereby recombinants exhibit the greatest replication,
followed by subtype D, followed by subtypes A and C. Our data identify Gag
protease as a major determinant of subtype differences in disease progression
among HIV-1 subtypes; furthermore, we propose that the poorer viral replicative
capacity of subtypes A and C may paradoxically contribute to their more efficient
spread in sub-Saharan Africa.
PMID- 28424287
TI - Protective Efficacies of Formaldehyde-Inactivated Whole-Virus Vaccine and
Antivirals in a Murine Model of Coxsackievirus A10 Infection.
AB - Coxsackievirus A10 (CVA10) is one of the major pathogens associated with hand,
foot, and mouth disease (HFMD). CVA10 infection can cause herpangina and viral
pneumonia, which can be complicated by severe neurological sequelae. The
morbidity and mortality of CVA10-associated HFMD have been increasing in recent
years, particularly in the pan-Pacific region. There are limited studies,
however, on the pathogenesis and immunology of CVA10-associated HFMD infections,
and few antiviral drugs or vaccines have been reported. In the present study, a
cell-adapted CVA10 strain was employed to inoculate intramuscularly 5-day-old ICR
mice, which developed significant clinical signs, including reduced mobility,
lower weight gain, and quadriplegia, with significant pathology in the brain,
hind limb skeletal muscles, and lungs of infected mice in the moribund state. The
severity of illness was associated with abnormally high expression of the
proinflammatory cytokine interleukin 6 (IL-6). Antiviral assays demonstrated that
ribavirin and gamma interferon administration could significantly inhibit CVA10
replication both in vitro and in vivo In addition, formaldehyde-inactivated CVA10
whole-virus vaccines induced immune responses in adult mice, and maternal
neutralizing antibodies could be transmitted to neonatal mice, providing
protection against CVA10 clinical strains. Furthermore, high-titer antisera were
effective against CVA10 and could relieve early clinical symptoms and improve the
survival rates of CVA10-challenged neonatal mice. In summary, we present a novel
murine model to study CVA10 pathology that will be extremely useful in developing
effective antivirals and vaccines to diminish the burden of HFMD-associated
disease.IMPORTANCE Hand, foot, and mouth disease cases in infancy, arising from
coxsackievirus A10 (CVA10) infections, are typically benign, resolving without
any significant adverse events. Severe disease and fatalities, however, can occur
in some children, necessitating the development of vaccines and antiviral
therapies. The present study has established a newborn-mouse model of CVA10 that,
importantly, recapitulates many aspects of human disease with respect to the
neuropathology and skeletal muscle pathology. We found that high levels of the
proinflammatory cytokine interleukin 6 correlated with disease severity and that
ribavirin and gamma interferon could decrease viral titers in vitro and in vivo
Whole-virus vaccines produced immune responses in adult mice, and immunized
mothers conferred protection on neonates against challenge from CVA10 clinical
strains. Passive immunization with high-titer antisera could also improve
survival rates in newborn animals.
PMID- 28424288
TI - Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of
Dendritic Cells.
AB - Viral protein R (Vpr) is an HIV-1 accessory protein whose function remains poorly
understood. In this report, we sought to determine the requirement of Vpr for
facilitating HIV-1 infection of monocyte-derived dendritic cells (MDDCs), one of
the first cell types to encounter virus in the peripheral mucosal tissues. In
this report, we characterize a significant restriction of Vpr-deficient virus
replication and spread in MDDCs alone and in cell-to-cell spread in MDDC-CD4+ T
cell cocultures. This restriction of HIV-1 replication in MDDCs was observed in a
single round of virus replication and was rescued by the expression of Vpr in
trans in the incoming virion. Interestingly, infections of MDDCs with viruses
that encode Vpr mutants unable to interact with either the DCAF1/DDB1 E3
ubiquitin ligase complex or a host factor hypothesized to be targeted for
degradation by Vpr also displayed a significant replication defect. While the
extent of proviral integration in HIV-1-infected MDDCs was unaffected by the
absence of Vpr, the transcriptional activity of the viral long terminal repeat
(LTR) from Vpr-deficient proviruses was significantly reduced. Together, these
results characterize a novel postintegration restriction of HIV-1 replication in
MDDCs and show that the interaction of Vpr with the DCAF1/DDB1 E3 ubiquitin
ligase complex and the yet-to-be-identified host factor might alleviate this
restriction by inducing transcription from the viral LTR. Taken together, these
findings identify a robust in vitro cell culture system that is amenable to
addressing mechanisms underlying Vpr-mediated enhancement of HIV-1
replication.IMPORTANCE Despite decades of work, the function of the HIV-1 protein
Vpr remains poorly understood, primarily due to the lack of an in vitro cell
culture system that demonstrates a deficit in replication upon infection with
viruses in the absence of Vpr. In this report, we describe a novel cell infection
system that utilizes primary human dendritic cells, which display a robust
decrease in viral replication upon infection with Vpr-deficient HIV-1. We show
that this replication difference occurs in a single round of infection and is due
to decreased transcriptional output from the integrated viral genome. Viral
transcription could be rescued by virion-associated Vpr. Using mutational
analysis, we show that domains of Vpr involved in binding to the DCAF1/DDB1/E3
ubiquitin ligase complex and prevention of cell cycle progression into mitosis
are required for LTR-mediated viral expression, suggesting that the
evolutionarily conserved G2 cell cycle arrest function of Vpr is essential for
HIV-1 replication.
PMID- 28424290
TI - Skin-derived precursors from human subjects with Type 2 diabetes yield
dysfunctional vascular smooth muscle cells.
AB - : Objective: Few methods enable molecular and cellular studies of vascular aging
or Type 2 diabetes (T2D). Here, we report a new approach to studying human
vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs
differentiated from progenitors found in skin. Approach and results: Skin-derived
precursors (SKPs) were cultured from biopsies (N=164, ~1 cm2) taken from the
edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7 +/-
13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at
high efficiency (>80% yield). The number of SKPs isolated from subjects with T2D
was ~50% lower than those without T2D (cells/g: 0.18 +/- 0.03, N=58 versus 0.40
+/- 0.05, N=100, P<0.05). Importantly, SKP-derived VSMCs from subjects with T2D
had higher Fluo-5F-determined baseline cytosolic Ca2+ concentrations (AU: 1,968
+/- 160, N=7 versus 1,386 +/- 170, N=13, P<0.05), and a trend toward greater Ca2+
cycling responses to norepinephrine (NE) (AUC: 177,207 +/- 24,669, N=7 versus
101,537 +/- 15,881, N=20, P<0.08) despite a reduced frequency of Ca2+ cycling
(events s-1 cell-1: 0.011 +/- 0.004, N=8 versus 0.021 +/- 0.003, N=19, P<0.05)
than those without T2D. SKP-derived VSMCs from subjects with T2D also manifest
enhanced sensitivity to phenylephrine (PE) in an impedance-based assay (EC50 nM:
72.3 +/- 63.6, N=5 versus 3,684 +/- 3,122, N=9, P<0.05), and impaired wound
closure in vitro (% closure: 21.9 +/- 3.6, N=4 versus 67.0 +/- 10.3, N=4,
P<0.05). Compared with aortic- and saphenous vein-derived primary VSMCs, SKP
derived VSMCs are functionally distinct, but mirror defects of T2D also exhibited
by primary VSMCs. CONCLUSION: Skin biopsies from older adults yield sufficient
SKPs to differentiate VSMCs, which reveal abnormal phenotypes of T2D that survive
differentiation and persist even after long-term normoglycemic culture.
PMID- 28424289
TI - Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of
Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68.
AB - Coxsackievirus A16 (CV-A16), CV-A6, and enterovirus D68 (EV-D68) belong to the
Picornaviridae family and are major causes of hand, foot, and mouth disease
(HFMD) and pediatric respiratory disease worldwide. The biological
characteristics of these viruses, especially their interplay with the host innate
immune system, have not been well investigated. In this study, we discovered that
the 3Cpro proteins from CV-A16, CV-A6, and EV-D68 bind melanoma differentiation
associated gene 5 (MDA5) and inhibit its interaction with MAVS. Consequently,
MDA5-triggered type I interferon (IFN) signaling in the retinoic acid-inducible
gene I-like receptor (RLR) pathway was blocked by the CV-A16, CV-A6, and EV-D68
3Cpro proteins. Furthermore, the CV-A16, CV-A6, and EV-D68 3Cpro proteins all
cleave transforming growth factor beta-activated kinase 1 (TAK1), resulting in
the inhibition of NF-kappaB activation, a host response also critical for Toll
like receptor (TLR)-mediated signaling. Thus, our data demonstrate that
circulating HFMD-associated CV-A16 and CV-A6, as well as severe respiratory
disease-associated EV-D68, have developed novel mechanisms to subvert host innate
immune responses by targeting key factors in the RLR and TLR pathways. Blocking
the ability of 3Cpro proteins from diverse enteroviruses and coxsackieviruses to
interfere with type I IFN induction should restore IFN antiviral function,
offering a potential novel antiviral strategy.IMPORTANCE CV-A16, CV-A6, and EV
D68 are emerging pathogens associated with hand, foot, and mouth disease and
pediatric respiratory disease worldwide. The pathogenic mechanisms of these
viruses are largely unknown. Here we demonstrate that the CV-A16, CV-A6, and EV
D68 3Cpro proteins block MDA5-triggered type I IFN induction. The 3Cpro proteins
of these viruses bind MDA5 and inhibit its interaction with MAVS. In addition,
the CV-A16, CV-A6, and EV-D68 3Cpro proteins cleave TAK1 to inhibit the NF-kappaB
response. Thus, our data demonstrate that circulating HFMD-associated CV-A16 and
CV-A6, as well as severe respiratory disease-associated EV-D68, have developed a
mechanism to subvert host innate immune responses by simultaneously targeting key
factors in the RLR and TLR pathways. These findings indicate the potential merit
of targeting the CV-A16, CV-A6, and EV-D68 3Cpro proteins as an antiviral
strategy.
PMID- 28424291
TI - Comparison of optomotor and optokinetic reflexes in mice.
AB - During animal locomotion or position adjustments, the visual system uses image
stabilization reflexes to compensate for global shifts in the visual scene. These
reflexes elicit compensatory head movements (optomotor response, OMR) in
unrestrained animals or compensatory eye movements (optokinetic response, OKR) in
head-fixed or unrestrained animals exposed to globally rotating striped patterns.
In mice, OMR are relatively easy to observe and find broad use in the rapid
evaluation of visual function. OKR determinations are more involved
experimentally but yield more stereotypical, easily quantifiable results. The
relative contributions of head and eye movements to image stabilization in mice
have not been investigated. We are using newly developed software and apparatus
to accurately quantitate mouse head movements during OMR, quantitate eye
movements during OKR, and determine eye movements in freely behaving mice. We
provide the first direct comparison of OMR and OKR gains (head or eye
velocity/stimulus velocity) and find that the two reflexes have comparable
dependencies on stimulus luminance, contrast, spatial frequency, and velocity.
OMR and OKR are similarly affected in genetically modified mice with defects in
retinal ganglion cells (RGC) compared with wild-type, suggesting they are driven
by the same sensory input (RGC type). OKR eye movements have much higher gains
than the OMR head movements, but neither can fully compensate global visual
shifts. However, combined eye and head movements can be detected in unrestrained
mice performing OMR, suggesting they can cooperate to achieve image
stabilization, as previously described for other species.NEW & NOTEWORTHY We
provide the first quantitation of head gain during optomotor response in mice and
show that optomotor and optokinetic responses have similar psychometric curves.
Head gains are far smaller than eye gains. Unrestrained mice combine head and eye
movements to respond to visual stimuli, and both monocular and binocular fields
are used during optokinetic responses. Mouse OMR and OKR movements are
heterogeneous under optimal and suboptimal stimulation and are affected in mice
lacking ON direction-selective retinal ganglion cells.
PMID- 28424292
TI - Loss and recovery of functional connectivity in cultured cortical networks
exposed to hypoxia.
AB - In the core of a brain infarct, loss of neuronal function is followed by neuronal
death within minutes. In an area surrounding the core (penumbra), some perfusion
remains. Here, neurons initially remain structurally intact, but massive synaptic
failure strongly reduces neural activity. Activity in the penumbra may eventually
recover or further deteriorate toward massive cell death. Besides activity
recovery, return of brain functioning requires restoration of connectivity.
However, low activity has been shown to initiate compensatory mechanisms that
affect network connectivity. We investigated the effect of transient hypoxia and
compensatory mechanisms on activity and functional connectivity using cultured
cortical networks on multielectrode arrays. Networks were exposed to hypoxia of
controlled depth (10-90% of normoxia) and duration (6-48 h). First, we determined
how hypoxic depth and duration govern activity recovery. Then, we investigated
connectivity changes during and after hypoxic incidents, mild enough for activity
to recover. Shortly after hypoxia onset, activity and connectivity decreased.
Following 4-6 h of ongoing hypoxia, we observed partial recovery. Only if the
hypoxic burden was limited did connectivity show further recovery upon return to
normoxia. Partial recovery during hypoxia was dominated by restored baseline
connections, rather than newly formed ones. Baseline strengths of surviving
(persisting or recovered) and lost connections did not differ nor did baseline
activity at their "presynaptic" electrodes. However, "postsynaptic" electrodes of
surviving connections were significantly more active during baseline than those
of lost connections. This implies that recovery during hypoxia reflects an
effective mechanism to restore network activity, which does not necessarily
conserve prehypoxia connectivity.NEW & NOTEWORTHY Hypoxia reduced the firing
rates of cultured neurons. Depending on hypoxic depth and duration, activity
recovered during hypoxia and upon return to normoxia. Recovery (partial) during
hypoxia was associated with restored baseline connections rather than newly
formed ones. Predominantly, baseline connections with most active postsynaptic
electrodes recovered, supporting the notion of effective activity homeostasis.
This compensatory mechanism remained effective during ~20 h of hypoxia. Beyond 20
h of compensation, loss of activity and connectivity became irreversible.
PMID- 28424293
TI - Prediction suppression and surprise enhancement in monkey inferotemporal cortex.
AB - Exposing monkeys, over the course of days and weeks, to pairs of images presented
in fixed sequence, so that each leading image becomes a predictor for the
corresponding trailing image, affects neuronal visual responsiveness in area TE.
At the end of the training period, neurons respond relatively weakly to a
trailing image when it appears in a trained sequence and, thus, confirms
prediction, whereas they respond relatively strongly to the same image when it
appears in an untrained sequence and, thus, violates prediction. This effect
could arise from prediction suppression (reduced firing in response to the
occurrence of a probable event) or surprise enhancement (elevated firing in
response to the omission of a probable event). To identify its cause, we compared
firing under the prediction-confirming and prediction-violating conditions to
firing under a prediction-neutral condition. The results provide strong evidence
for prediction suppression and limited evidence for surprise enhancement.NEW &
NOTEWORTHY In predictive coding models of the visual system, neurons carry signed
prediction error signals. We show here that monkey inferotemporal neurons exhibit
prediction-modulated firing, as posited by these models, but that the signal is
unsigned. The response to a prediction-confirming image is suppressed, and the
response to a prediction-violating image may be enhanced. These results are
better explained by a model in which the visual system emphasizes unpredicted
events than by a predictive coding model.
PMID- 28424294
TI - GABA and primary motor cortex inhibition in young and older adults: a multimodal
reliability study.
AB - The effects of healthy aging on gamma-aminobutyric acid (GABA) within primary
motor cortex (M1) remain poorly understood. Studies have reported contrasting
results, potentially due to limitations with the common assessment technique. The
aim of the present study was to investigate the effect of healthy aging on M1
GABA concentration and neurotransmission using a multimodal approach. Fifteen
young and sixteen older adults participated in this study. Magnetic resonance
spectroscopy (MRS) was used to measure M1 GABA concentration. Single-pulse and
threshold-tracking paired-pulse transcranial magnetic stimulation (TMS) protocols
were used to examine cortical silent period duration, short- and long-interval
intracortical inhibition (SICI and LICI), and late cortical disinhibition (LCD).
The reliability of TMS measures was examined with intraclass correlation
coefficient analyses. SICI at 1 ms was reduced in older adults (15.13 +/- 2.59%)
compared with young (25.66 +/- 1.44%; P = 0.002). However, there was no age
related effect for cortical silent period duration, SICI at 3 ms, LICI, or LCD
(all P > 0.66). The intersession reliability of threshold-tracking measures was
good to excellent for both young (range 0.75-0.96) and older adults (range 0.88
0.93). Our findings indicate that extrasynaptic inhibition may be reduced with
advancing age, whereas GABA concentration and synaptic inhibition are maintained.
Furthermore, MRS and threshold-tracking TMS provide valid and reliable assessment
of M1 GABA concentration and neurotransmission, respectively, in young and older
adults.NEW & NOTEWORTHY gamma-Aminobutyric acid (GABA) in primary motor cortex
was assessed in young and older adults using magnetic resonance spectroscopy and
threshold-tracking paired-pulse transcranial magnetic stimulation. Older adults
exhibited reduced extrasynaptic inhibition (short-interval intracortical
inhibition at 1 ms) compared with young, whereas GABA concentration and synaptic
inhibition were similar between age groups. We demonstrate that magnetic
resonance spectroscopy and threshold-tracking provide valid and reliable
assessments of primary motor cortex GABA concentration and neurotransmission,
respectively.
PMID- 28424295
TI - The sensorimotor system minimizes prediction error for object lifting when the
object's weight is uncertain.
AB - A reliable mechanism to predict the heaviness of an object is important for
manipulating an object under environmental uncertainty. Recently, Cashaback et
al. (Cashaback JGA, McGregor HR, Pun HCH, Buckingham G, Gribble PL. J
Neurophysiol 117: 260-274, 2017) showed that for object lifting the sensorimotor
system uses a strategy that minimizes prediction error when the object's weight
is uncertain. Previous research demonstrates that visually guided reaching is
similarly optimized. Although this suggests a unified strategy of the
sensorimotor system for object manipulation, the selected strategy appears to be
task dependent and subject to change in response to the degree of environmental
uncertainty.
PMID- 28424298
TI - Stress-Related Memory Impairments Are Modulated by the Synergistic Action of
Stress Hormones: Implications for PTSD.
PMID- 28424297
TI - Magnitude and behavior of cross-talk effects in multichannel electrophysiology
experiments.
AB - Modern neurophysiological experiments frequently involve multiple channels
separated by very small distances. A unique methodological concern for multiple
electrode experiments is that of capacitive coupling (cross-talk) between
channels. Yet the nature of the cross-talk recording circuit is not well known in
the field, and the extent to which it practically affects neurophysiology
experiments has never been fully investigated. Here we describe a simple
electrical circuit model of simultaneous recording and stimulation with two or
more channels and experimentally verify the model using ex vivo brain slice and
in vivo whole-brain preparations. In agreement with the model, we find that cross
talk amplitudes increase nearly linearly with the impedance of a recording
electrode and are larger for higher frequencies. We demonstrate cross-talk
contamination of action potential waveforms from intracellular to extracellular
channels, which is observable in part because of the different orders of
magnitude between the channels. This contamination is electrode impedance
dependent and matches predictions from the model. We use recently published
parameters to simulate cross-talk in high-density multichannel extracellular
recordings. Cross-talk effectively spatially smooths current source density (CSD)
estimates in these recordings and induces artefactual phase shifts where
underlying voltage gradients occur; however, these effects are modest. We show
that the effects of cross-talk are unlikely to affect most conclusions inferred
from neurophysiology experiments when both originating and receiving electrode
record signals of similar magnitudes. We discuss other types of experiments and
analyses that may be susceptible to cross-talk, techniques for detecting and
experimentally reducing cross-talk, and implications for high-density probe
design.NEW & NOTEWORTHY We develop and experimentally verify an electrical
circuit model describing cross-talk that necessarily occurs between two channels.
Recorded cross-talk increased with electrode impedance and signal frequency. We
recorded cross-talk contamination of spike waveforms from intracellular to
extracellular channels. We simulated high-density multichannel extracellular
recordings and demonstrate spatial smoothing and phase shifts that cross-talk
enacts on CSD measurements. However, when channels record similar-magnitude
signals, effects are modest and unlikely to affect most conclusions.
PMID- 28424299
TI - Adult Neural Stem Cell Multipotency and Differentiation Are Directed by the
Methyl-CpG-Binding Protein MBD1.
PMID- 28424296
TI - Cell type-specific changes in retinal ganglion cell function induced by rod death
and cone reorganization in rats.
AB - We have determined the impact of rod death and cone reorganization on the
spatiotemporal receptive fields (RFs) and spontaneous activity of distinct
retinal ganglion cell (RGC) types. We compared RGC function between healthy and
retinitis pigmentosa (RP) model rats (S334ter-3) at a time when nearly all rods
were lost but cones remained. This allowed us to determine the impact of rod
death on cone-mediated visual signaling, a relevant time point because the
diagnosis of RP frequently occurs when patients are nightblind but daytime vision
persists. Following rod death, functionally distinct RGC types persisted; this
indicates that parallel processing of visual input remained largely intact.
However, some properties of cone-mediated responses were altered ubiquitously
across RGC types, such as prolonged temporal integration and reduced spatial RF
area. Other properties changed in a cell type-specific manner, such as temporal
RF shape (dynamics), spontaneous activity, and direction selectivity. These
observations identify the extent of functional remodeling in the retina following
rod death but before cone loss. They also indicate new potential challenges to
restoring normal vision by replacing lost rod photoreceptors.NEW & NOTEWORTHY
This study provides novel and therapeutically relevant insights to retinal
function following rod death but before cone death. To determine changes in
retinal output, we used a large-scale multielectrode array to simultaneously
record from hundreds of retinal ganglion cells (RGCs). These recordings of large
scale neural activity revealed that following the death of all rods, functionally
distinct RGCs remain. However, the receptive field properties and spontaneous
activity of these RGCs are altered in a cell type-specific manner.
PMID- 28424301
TI - Patient confidentiality and autonomy: how do we account for coercive control?
PMID- 28424302
TI - Assessing the safety culture of care homes: a multimethod evaluation of the
adaptation, face validity and feasibility of the Manchester Patient Safety
Framework.
AB - BACKGROUND: Understanding the cultural characteristics of healthcare
organisations is widely recognised to be an important component of patient
safety. A growing number of vulnerable older people are living in care homes but
little attention has been paid to safety culture in this sector. In this study,
we aimed to adapt the Manchester Patient Safety Framework (MaPSaF), a commonly
used tool in the health sector, for use in care homes and then to test its face
validity and preliminary feasibility as a tool for developing a better
understanding of safety culture in the sector. METHODS: As part of a wider
improvement programme to reduce the prevalence of common safety incidents among
residents in 90 care homes in England, we adapted MaPSaF and carried out a
multimethod participatory evaluation of its face validity and feasibility for
care home staff. Data were collected using participant observation, interviews,
documentary analysis and a survey, and were analysed thematically. RESULTS:
MaPSaF required considerable adaptation in terms of its length, language and
content in order for it to be perceived to be acceptable and useful to care home
staff. The changes made reflected differences between the health and care home
sectors in terms of the local context and wider policy environment, and the
expectations, capacity and capabilities of the staff. Based on this preliminary
study, the adapted tool, renamed 'Culture is Key', appears to have reasonable
face validity and, with adequate facilitation, it is usable by front-line staff
and useful in raising their awareness about safety issues. CONCLUSIONS: 'Culture
is Key' is a new tool which appears to have acceptable face validity and
feasibility to be used by care home staff to deepen their understanding of the
safety culture of their organisations and therefore has potential to contribute
to improving care for vulnerable older people.
PMID- 28424303
TI - Distribution of genotype network sizes in sequence-to-structure genotype
phenotype maps.
AB - An essential quantity to ensure evolvability of populations is the navigability
of the genotype space. Navigability, understood as the ease with which
alternative phenotypes are reached, relies on the existence of sufficiently large
and mutually attainable genotype networks. The size of genotype networks (e.g.
the number of RNA sequences folding into a particular secondary structure or the
number of DNA sequences coding for the same protein structure) is astronomically
large in all functional molecules investigated: an exhaustive experimental or
computational study of all RNA folds or all protein structures becomes impossible
even for moderately long sequences. Here, we analytically derive the distribution
of genotype network sizes for a hierarchy of models which successively
incorporate features of increasingly realistic sequence-to-structure genotype
phenotype maps. The main feature of these models relies on the characterization
of each phenotype through a prototypical sequence whose sites admit a variable
fraction of letters of the alphabet. Our models interpolate between two limit
distributions: a power-law distribution, when the ordering of sites in the
prototypical sequence is strongly constrained, and a lognormal distribution, as
suggested for RNA, when different orderings of the same set of sites yield
different phenotypes. Our main result is the qualitative and quantitative
identification of those features of sequence-to-structure maps that lead to
different distributions of genotype network sizes.
PMID- 28424304
TI - Giant axonal neuropathy alters the structure of keratin intermediate filaments in
human hair.
AB - Giant axonal neuropathy (GAN) follows an autosomal recessive genetic inheritance
and impedes the peripheral and central nervous system due to axonal swellings
that are packed with neurofilaments. The patients display a number of phenotypes,
including hypotonia, muscle weakness, decreased reflexes, ataxia, seizures,
intellectual disability, pale skin and often curled hair. We used X-ray
diffraction and tensile testing to determine potential changes to the structure
of keratin intermediate filaments (IFs) in the hair of patients with GAN. A
statistically significant decrease in the 47 and the 27 A diffraction signals
were observed. Tensile tests determined that the hair was slightly stiffer,
stronger and more extensible in GAN patients. These results suggest that the
structure of keratin IFs in hair is altered in GAN, and the findings are
compatible with an increased positional disorder of the keratin tetramers within
the hair fibres.
PMID- 28424306
TI - Sociable crayfish get drunk more easily than loners.
PMID- 28424305
TI - Numerical simulation of haemodynamics and low-density lipoprotein transport in
the rabbit aorta and their correlation with atherosclerotic plaque thickness.
AB - Two mechanisms of shear stress and mass transport have been recognized to play an
important role in the development of localized atherosclerosis. However, their
relationship and roles in atherogenesis are still obscure. It is necessary to
investigate quantitatively the correlation among low-density lipoproteins (LDL)
transport, haemodynamic parameters and plaque thickness. We simulated blood flow
and LDL transport in rabbit aorta using computational fluid dynamics and
evaluated plaque thickness in the aorta of a high-fat-diet rabbit. The numerical
results show that regions with high luminal LDL concentration tend to have
severely negative haemodynamic environments (HEs). However, for regions with
moderately and slightly high luminal LDL concentration, the relationship between
LDL concentration and the above haemodynamic indicators is not clear cut. Point
by-point correlation with experimental results indicates that severe
atherosclerotic plaque corresponds to high LDL concentration and seriously
negative HEs, less severe atherosclerotic plaque is related to either moderately
high LDL concentration or moderately negative HEs, and there is almost no
atherosclerotic plaque in regions with both low LDL concentration and positive
HEs. In conclusion, LDL distribution is closely linked to blood flow transport,
and the synergetic effects of luminal surface LDL concentration and wall shear
stress-based haemodynamic indicators may determine plaque thickness.
PMID- 28424308
TI - Spinner dolphin SCUBA tanks develop no faster.
PMID- 28424307
TI - Archer fish jump as well as shoot.
PMID- 28424309
TI - Painkillers relieve zebrafish larvae discomfort.
PMID- 28424310
TI - Heart rate regulation in diving sea lions: the vagus nerve rules.
AB - Recent publications have emphasized the potential generation of morbid cardiac
arrhythmias secondary to autonomic conflict in diving marine mammals. Such
conflict, as typified by cardiovascular responses to cold water immersion in
humans, has been proposed to result from exercise-related activation of cardiac
sympathetic fibers to increase heart rate, combined with depth-related changes in
parasympathetic tone to decrease heart rate. After reviewing the marine mammal
literature and evaluating heart rate profiles of diving California sea lions
(Zalophus californianus), we present an alternative interpretation of heart rate
regulation that de-emphasizes the concept of autonomic conflict and the risk of
morbid arrhythmias in marine mammals. We hypothesize that: (1) both the
sympathetic cardiac accelerator fibers and the peripheral sympathetic vasomotor
fibers are activated during dives even without exercise, and their activities are
elevated at the lowest heart rates in a dive when vasoconstriction is maximal,
(2) in diving animals, parasympathetic cardiac tone via the vagus nerve dominates
over sympathetic cardiac tone during all phases of the dive, thus producing the
bradycardia, (3) adjustment in vagal activity, which may be affected by many
inputs, including exercise, is the primary regulator of heart rate and heart rate
fluctuations during diving, and (4) heart beat fluctuations (benign arrhythmias)
are common in marine mammals. Consistent with the literature and with these
hypotheses, we believe that the generation of morbid arrhythmias because of
exercise or stress during dives is unlikely in marine mammals.
PMID- 28424311
TI - Mechanics of the thorax in flies.
AB - Insects represent more than 60% of all multicellular life forms, and are easily
among the most diverse and abundant organisms on earth. They evolved functional
wings and the ability to fly, which enabled them to occupy diverse niches.
Insects of the hyper-diverse orders show extreme miniaturization of their body
size. The reduced body size, however, imposes steep constraints on flight
ability, as their wings must flap faster to generate sufficient forces to stay
aloft. Here, we discuss the various physiological and biomechanical adaptations
of the thorax in flies which enabled them to overcome the myriad constraints of
small body size, while ensuring very precise control of their wing motion. One
such adaptation is the evolution of specialized myogenic or asynchronous muscles
that power the high-frequency wing motion, in combination with neurogenic or
synchronous steering muscles that control higher-order wing kinematic patterns.
Additionally, passive cuticular linkages within the thorax coordinate fast and
yet precise bilateral wing movement, in combination with an actively controlled
clutch and gear system that enables flexible flight patterns. Thus, the study of
thoracic biomechanics, along with the underlying sensory-motor processing, is
central in understanding how the insect body form is adapted for flight.
PMID- 28424312
TI - Archer fish jumping prey capture: kinematics and hydrodynamics.
AB - Smallscale archer fish, Toxotes microlepis, are best known for spitting jets of
water to capture prey, but also hunt by jumping out of the water to heights of up
to 2.5 body lengths. In this study, high-speed imaging and particle image
velocimetry were used to characterize the kinematics and hydrodynamics of this
jumping behavior. Jumping used a set of kinematics distinct from those of in
water feeding strikes and was segmented into three phases: (1) hovering to sight
prey at the surface, (2) rapid upward thrust production and (3) gliding to the
prey once out of the water. The number of propulsive tail strokes positively
correlated with the height of the bait, as did the peak body velocity observed
during a jump. During the gliding stage, the fish traveled ballistically; the
kinetic energy when the fish left the water balanced with the change in potential
energy from water exit to the maximum jump height. The ballistic estimate of the
mechanical energy required to jump was comparable with the estimated mechanical
energy requirements of spitting a jet with sufficient momentum to down prey and
subsequently pursuing the prey in water. Particle image velocimetry showed that,
in addition to the caudal fin, the wakes of the anal, pectoral and dorsal fins
were of nontrivial strength, especially at the onset of thrust production. During
jump initiation, these fins were used to produce as much vertical acceleration as
possible given the spatial constraint of starting directly at the water's surface
to aim.
PMID- 28424313
TI - Reduction in activity by noxious chemical stimulation is ameliorated by immersion
in analgesic drugs in zebrafish.
AB - Research has recently demonstrated that larval zebrafish show similar molecular
responses to nociception to those of adults. Our study explored whether
unprotected larval zebrafish exhibited altered behaviour after exposure to
noxious chemicals and screened a range of analgesic drugs to determine their
efficacy to reduce these responses. This approach aimed to validate larval
zebrafish as a reliable replacement for adults as well as providing a high
throughput means of analysing behavioural responses. Zebrafish at 5 days post
fertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and
0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each was
recorded and analysed using novel tracking software that measures time spent
active in 25 larvae at one time. Subsequently, the efficacy of aspirin,
lidocaine, morphine and flunixin as analgesics after exposure to 0.1% acetic acid
was tested. Larvae exposed to 0.1% and 0.25% acetic acid spent less time active,
whereas those exposed to 0.01% acetic acid and 0.1-5% citric acid showed an
increase in swimming activity. Administration of 2.5 mg l-1 aspirin, 5 mg l-1
lidocaine and 48 mg l-1 morphine prevented the behavioural changes induced by
acetic acid. These results suggest that larvae respond to a noxious challenge in
a similar way to adult zebrafish and other vertebrates and that the effect of
nociception on activity can be ameliorated by using analgesics. Therefore,
adopting larval zebrafish could represent a direct replacement of a protected
adult fish with a non-protected form in pain- and nociception-related research.
PMID- 28424314
TI - Muscle biochemistry of a pelagic delphinid (Stenella longirostris longirostris):
insight into fishery-induced separation of mothers and calves.
AB - The length of time required for postnatal maturation of the locomotor muscle
(longissimus dorsi) biochemistry [myoglobin (Mb) content and buffering capacity]
in marine mammals typically varies with nursing duration, but it can be
accelerated by species-specific behavioral demands, such as deep-diving and sub
ice transit. We examined how the swimming demands of a pelagic lifestyle
influence postnatal maturation of Mb and buffering capacity in spinner dolphins
(Stenella longirostris longirostris). Mb content of newborn (1.16+/-0.07 g Mb per
100 g wet muscle mass, n=6) and juvenile (2.77+/-0.22 g per 100 g, n=4) spinner
dolphins were only 19% and 46% of adult levels (6.00+/-0.74 g per 100 g, n=6),
respectively. At birth, buffering capacity was 52.70+/-4.48 slykes (n=6) and
increased to 78.53+/-1.91 slykes (n=6) once a body length of 141 cm was achieved,
representing 1.6- to 2.0-year-old dolphins. Based on the age of weaning (1.3-1.6
years post-partum), muscle maturation occurred just after weaning as described
for coastal bottlenose dolphins (Tursiops truncatus). Thus, a pelagic lifestyle
does not promote rapid maturation of muscle biochemistry. Rather, it promotes
enhanced muscle biochemistry: newborn and adult spinner dolphins had four- and
two-times greater Mb contents than newborn and adult bottlenose dolphins,
respectively. Indeed, adult levels rivaled those of deep-diving cetaceans.
Nonetheless, the relatively underdeveloped muscle biochemistry of calves likely
contributes to documented mother-calf separations for spinner dolphins chased by
the tuna purse-seine fishery.
PMID- 28424315
TI - Prior social experience affects the behavioral and neural responses to acute
alcohol in juvenile crayfish.
AB - The effects of alcohol on society can be devastating, both as an immediate
consequence of acute intoxication and as a powerful drug of abuse. However, the
neurocellular mechanisms of alcohol intoxication are still elusive, partly
because of the complex interactions between alcohol and nervous system function.
We found that juvenile crayfish are behaviorally sensitive to acute alcohol
exposure and progress through stages that are strikingly similar to those of most
other intoxicated organisms. Most surprisingly, we found that the social history
of the animals significantly modified the acute effects of alcohol. Crayfish
taken from a rich social environment became intoxicated more rapidly than animals
that were socially isolated before alcohol exposure. In addition, we found that
the modulation of intoxicated behaviors by prior social experience was paralleled
on the level of individual neurons. These results significantly improve our
understanding of the mechanisms underlying the interplay between social
experience, alcohol intoxication and nervous system function.
PMID- 28424316
TI - Correction: Lombard effect onset times reveal the speed of vocal plasticity in a
songbird.
PMID- 28424317
TI - The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and
social anxiety in a healthy population.
AB - The neurohormone oxytocin plays a central role in human social behaviour and
cognition, and oxytocin dysregulation may contribute to psychiatric disorders.
However, genetic factors influencing individual variation in the oxytocinergic
system remain poorly understood. We genotyped 169 healthy adults for a functional
polymorphism in GTF2I (general transcription factor II-I), a gene associated with
high prosociality and reduced social anxiety in Williams syndrome, a condition
reported to involve high oxytocin levels and reactivity. Participants' salivary
oxytocin levels were measured before and after watching a validated empathy
inducing video. Oxytocin reactivity, defined as pre- to post-video percentage
change in salivary oxytocin, varied substantially and significantly between
individuals with different GTF2I genotypes, with, additionally, a trend towards
an interaction between genotype and sex. Individuals with more oxytocin-reactive
genotypes also reported significantly lower social anxiety. These findings
suggest a model whereby GTF2I has a continuum of effects on human sociality, from
the extreme social phenotypes and oxytocin dysregulation associated with gene
deletion in Williams syndrome, to individual differences in oxytocin reactivity
and sociality associated with common polymorphisms in healthy populations.
PMID- 28424318
TI - Infection dynamics of Mycoplasma hyorhinis in three commercial pig populations.
AB - Mycoplasma hyorhinis is one of the causative agents of polyserositis and
arthritis inpostweaning pigs. Knowledge regarding colonisation frequency and age
distribution inmodern pig production is lacking. The objective of this study was
to estimate the prevalenceof M hyorhinis colonisation in different age groups
across three commercial pig populations.Nasal swabs were collected from sows,
piglets and nursery pigs of different ages. Oral fluidswere collected from
nursery pigs. Necropsies were performed to assess the presence ofM hyorhinis
associated disease. M hyorhinis was detected in 5/60 sows in herd A, 3/60 inherd
B and none in herd C. In herd A and B, the prevalence was low in preweaning
piglets(~8 per cent) and high in postweaning pigs (~98 per cent). A total of 7/8
oral fluids testedPCR positive in herds A and B, while 1/8 tested positive in
herd C. In herd C, the preweaningand postweaning prevalence was low. In herds A
and B, necropsied pigs had polyserositislesions where M hyorhinis was detected by
PCR. This study showed that prevalence ofM hyorhinis colonisation varies with pig
age and across farms. Information generated will aidin the design and
implementation of control and prevention strategies.
PMID- 28424319
TI - A survey on antimicrobial resistant Escherichia coli isolated from unpasteurised
cows' milk in Northern Ireland.
PMID- 28424321
TI - The Drosophila ZO-1 protein Polychaetoid suppresses Deltex-regulated Notch
activity to modulate germline stem cell niche formation.
AB - The developmental signalling protein Notch can be proteolytically activated
following ligand-interaction at the cell surface, or can be activated
independently of its ligands, following Deltex (Dx)-induced Notch endocytosis and
trafficking to the lysosomal membrane. The means by which different pools of
Notch are directed towards these alternative outcomes remains poorly understood.
We found that the Drosophila ZO-1 protein Polychaetoid (Pyd) suppresses
specifically the Dx-induced form of Notch activation both in vivo and in cell
culture assays. In vivo we confirmed the physiological relevance and direction of
the Pyd/Dx interaction by showing that the expanded ovary stem cell niche
phenotypes of pyd mutants require the presence of functional Dx and other
components that are specific to the Dx-induced Notch activation mechanism. In S2
cells we found that Pyd can form a complex with Dx and Notch at the cell surface
and reduce Dx-induced Notch endocytosis. Similar to other known activities of ZO
1 family proteins, the action of Pyd on Dx-induced endocytosis and signalling was
found to be cell density dependent. Thus, together, our results suggest an
alternative means by which external cues can tune Notch signalling through Pyd
regulation of Dx-induced Notch trafficking.
PMID- 28424322
TI - Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS): A Rare but Potentially
Treatable Condition.
AB - Kaposi sarcoma inflammatory cytokine syndrome (KICS) is a newly-described
condition affecting individuals who are HIV-positive and are infected with human
herpesvirus 8 (HHV-8). This is a syndrome that in some ways mimics severe sepsis
with associated acute respiratory distress syndrome, possibly requiring a
ventilator and vasopressor support. However, unlike severe sepsis, antibiotics
provide no benefit. Management of KICS has not been fully elucidated because of
its high mortality rate. However, the syndrome has been successfully treated in
some cases with immunomodulatory therapy. It is crucial for oncologists to be
able to recognize this syndrome and to institute the appropriate therapy. The
Oncologist 2017;22:623-625.
PMID- 28424320
TI - TRPA1 expression and its functional activation in rodent cortex.
AB - TRPA1 is a non-selective cation channel involved in pain sensation and neurogenic
inflammation. Although TRPA1 is well established in a number of organs including
the nervous system, its presence and function in the mammalian cortex remains
unclear. Here, we demonstrate the expression of TRPA1 in rodent somatosensory
cortex through immunostaining and investigate its functional activation by whole
cell electrophysiology, Ca2+ imaging and two-photon photoswitching. Application
of TRPA1 agonist (AITC) and antagonist (HC-030031) produced significant
modulation of activity in layer 5 (L5) pyramidal neurons in both rats and mice;
AITC increased intracellular Ca2+ concentrations and depolarized neurons, and
both effects were blocked by HC-030031. These modulations were absent in the
TRPA1 knockout mice. Next, we used optovin, a reversible photoactive molecule, to
activate TRPA1 in individual L5 neurons of rat cortex. Optical control of
activity was established by applying a tightly focused femtosecond-pulsed laser
to optovin-loaded neurons. Light application depolarized neurons (n = 17) with
the maximal effect observed at lambda = 720 nm. Involvement of TRPA1 was further
confirmed by repeating the experiment in the presence of HC-030031, which
diminished the light modulation. These results demonstrate the presence of TRPA1
in L5 pyramidal neurons and introduce a highly specific approach to further
understand its functional significance.
PMID- 28424323
TI - Dosing Three-Drug Combinations That Include Targeted Anti-Cancer Agents: Analysis
of 37,763 Patients.
AB - BACKGROUND: Combining targeted and cytotoxic agents has the potential to improve
efficacy and attenuate resistance for metastatic cancer. Information regarding
safe starting doses for clinical trials of novel three-drug combinations is
lacking. MATERIALS AND METHODS: Published phase I-III adult oncology clinical
trials of three-drug combinations involving a targeted agent were identified by
PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was
calculated to compare the dose used in combination to the single agent
recommended dose: (U.S. Food and Drug Administration-approved/recommended phase
II dose/maximum tolerated dose). The additive dose percentage was the sum of the
dose percentages for each drug in the combination. RESULTS: A total of 37,763
subjects and 243 drug combinations were included. Only 28% of studies could give
each of the three agents at 100%. For combinations involving two targeted agents
and a cytotoxic agent, the lowest starting additive dose percentage was 133%,
which increased to 250% if two antibodies were included. For combinations of one
targeted agent and two cytotoxic agents, the lowest additive safe dose percentage
was 137%. When both cytotoxic agents were held at 100%, as occurred in 56% of
studies (which generally used cytotoxic doublets with known combination safety
dosing), the lowest safe dose percentage was 225% (providing that a histone
deacetylase inhibitor was not the targeted agent). CONCLUSION: These findings
serve as a safe starting point for dosing novel three-drug combinations involving
a targeted agent in clinical trials and practice. The Oncologist 2017;22:576-584
IMPLICATIONS FOR PRACTICE: Targeted and cytotoxic drug combinations can improve
efficacy and overcome resistance. More knowledge of safe starting doses would
facilitate use of combinations in clinical trials and practice. Analysis of
37,763 subjects (243 combinations) showed three drugs could be safely
administered, but less than 30% of combinations could include all three drugs at
full dose. Dose reductions to 45% of the dose of each single agent may be
required. Combinations involving two antibodies required fewer dose reductions,
and the use of established cytotoxic doublets made initial dose assignment
easier.
PMID- 28424324
TI - Preventing Venous Thromboembolism in Ambulatory Cancer Patients: The ONKOTEV
Study.
AB - BACKGROUND: The efficacy of risk model scores to predict venous thromboembolism
(VTE) in ambulatory cancer patients is under investigation, aiming to stratify on
an individual risk basis the subset of the cancer population that could mostly
benefit from primary thromboprophylaxis. MATERIALS AND METHODS: We prospectively
assessed 843 patients with active cancers, collecting clinical and laboratory
data. We screened all the patients with a duplex ultrasound (B-mode imaging and
Doppler waveform analysis) of the upper and lower limbs to evaluate the right
incidence of VTE (both asymptomatic and symptomatic). The efficacy of the
existing Khorana risk model in preventing VTE was also explored in our
population. Several risk factors associated with VTE were analyzed, leading to
the construction of a risk model. The Fine and Gray model was used to account for
death as a competing risk in the derivation of the new model. RESULTS: The risk
factors significantly associated with VTE at univariate analysis and further
confirmed in the multivariate analysis, after bootstrap validation, were the
presence of metastatic disease, the compression of vascular/lymphatic structures
by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent
receiving operating characteristic (ROC) curve analysis showed a significant
improvement in the area under the curve of the new score over the Khorana model
at 3 months (71.9% vs. 57.9%, p = .001), 6 months (75.4% vs. 58.6%, p < .001),
and 12 months (69.8% vs. 58.3%, p = .014). CONCLUSION: ONKOTEV score steps into
history of cancer-related-VTE as a promising tool to drive the decision about
primary prophylaxis in cancer outpatients. The validation represents the goal of
the prospective ONKOTEV-2 study, endorsed and approved by the European
Organization for Research and Treatment of Cancer Young Investigators Program.
The Oncologist 2017;22:601-608 IMPLICATIONS FOR PRACTICE: Preventing venous
thromboembolism in cancer outpatients with a risk model score will drive
physicians' decision of starting thromboprophylaxis in high-risk patients.
PMID- 28424325
TI - FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive
Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.
AB - : Until recently in the United States, no products were approved for second-line
treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and
Drug Administration approved atezolizumab for the treatment of patients with
locally advanced or metastatic urothelial carcinoma whose disease progressed
during or following platinum-containing chemotherapy or within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and
represents the first approved product directed against PD-L1. This accelerated
approval was based on results of a single-arm trial in 310 patients with locally
advanced or metastatic urothelial carcinoma who had disease progression after
prior platinum-containing chemotherapy. Patients received atezolizumab 1,200 mg
intravenously every 3 weeks until disease progression or unacceptable toxicity.
Key efficacy measures were objective response rate (ORR), as assessed by
Independent Review per RECIST 1.1, and duration of response (DoR). With a median
follow-up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all
treated patients. Median DoR was not reached and response durations ranged from
2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response
for >= 6 months. The most common adverse reactions (>=20%) were fatigue,
decreased appetite, nausea, urinary tract infection, pyrexia, and constipation.
Infection and immune-related adverse events also occurred, including pneumonitis,
hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit-risk
assessment was favorable to support accelerated approval. The observed clinical
benefits need to be verified in confirmatory trial(s). IMPLICATIONS FOR PRACTICE:
This accelerated approval of atezolizumab for second-line use in advanced
urothelial carcinoma provides patients with an effective, novel treatment option
for the management of their disease. This represents the first immunotherapy
approved in this disease setting.
PMID- 28424326
TI - Anti-tau antibody administration increases plasma tau in transgenic mice and
patients with tauopathy.
AB - Tauopathies are a group of disorders in which the cytosolic protein tau
aggregates and accumulates in cells within the brain, resulting in
neurodegeneration. A promising treatment being explored for tauopathies is
passive immunization with anti-tau antibodies. We previously found that
administration of an anti-tau antibody to human tau transgenic mice increased the
concentration of plasma tau. We further explored the effects of administering an
anti-tau antibody on plasma tau. After peripheral administration of an anti-tau
antibody to human patients with tauopathy and to mice expressing human tau in the
central nervous system, there was a dose-dependent increase in plasma tau. In
mouse plasma, we found that tau had a short half-life of 8 min that increased to
more than 3 hours after administration of anti-tau antibody. As tau transgenic
mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid
tau decreased. Administration of anti-tau antibody to tau transgenic mice that
had decreased brain soluble tau and interstitial fluid tau resulted in an
increase in plasma tau, but this increase was less than that observed in tau
transgenic mice without these brain changes. Tau transgenic mice subjected to
acute neuronal injury using 3-nitropropionic acid showed increased interstitial
fluid tau and plasma tau. These data suggest that peripheral administration of an
anti-tau antibody results in increased plasma tau, which correlates with the
concentration of extracellular and soluble tau in the brain.
PMID- 28424328
TI - Toward off-the-shelf adoptive T cell therapies.
AB - Artificial thymic organoids may enable more efficient engineered T cell
production for immunotherapy.
PMID- 28424327
TI - RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and
immune-mediated tissue injury.
AB - The molecular pathways that regulate the tissue repair function of type I
interferon (IFN-I) during acute tissue damage are poorly understood. We describe
a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute
tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein
(MAVS) were more sensitive to total body irradiation- and chemotherapy-induced
intestinal barrier damage. These mice developed worse graft-versus-host disease
(GVHD) in a preclinical model of allogeneic hematopoietic stem cell
transplantation (allo-HSCT) than did wild-type mice. This phenotype was not
associated with changes in the intestinal microbiota but was associated with
reduced gut epithelial integrity. Conversely, targeted activation of the RIG-I
pathway during tissue injury promoted gut barrier integrity and reduced GVHD.
Recombinant IFN-I or IFN-I expression induced by RIG-I promoted growth of
intestinal organoids in vitro and production of the antimicrobial peptide
regenerating islet-derived protein 3 gamma (RegIIIgamma). Our findings were not
confined to RIG-I/MAVS signaling because targeted engagement of the STING
(stimulator of interferon genes) pathway also protected gut barrier function and
reduced GVHD. Consistent with this, STING-deficient mice suffered worse GVHD
after allo-HSCT than did wild-type mice. Overall, our data suggest that
activation of either RIG-I/MAVS or STING pathways during acute intestinal tissue
injury in mice resulted in IFN-I signaling that maintained gut epithelial barrier
integrity and reduced GVHD severity. Targeting these pathways may help to prevent
acute intestinal injury and GVHD during allogeneic transplantation.
PMID- 28424329
TI - A paternal diet for offspring success?
AB - Supplementation of the diet of male mice with methyl donors, such as methionine
and folic acid, prior to mating impaired learning, memory, and metabolic
functions in the offspring.
PMID- 28424330
TI - Combination of an oncolytic virus with PD-L1 blockade keeps cancer in check.
AB - An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade
significantly reduces tumor burden and improves survival in murine cancer models.
PMID- 28424331
TI - Filtering more than light in the developing retina.
AB - Restricting transcytosis is essential for blood-retinal barrier formation.
PMID- 28424333
TI - Clinical chemoproteomics-Opportunities and obstacles.
AB - Chemoproteomics is the large-scale study of proteins using chemical methods.
Although chemoproteomic techniques are becoming commonplace in preclinical
research, few examples have found clinical utility. We explore the prospects for
advancing chemoproteomics into the clinical setting to understand drug-target
interactions and to identify new therapeutically relevant targets.
PMID- 28424335
TI - A Conversation with Raghu Kalluri.
PMID- 28424332
TI - Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.
AB - Exome and whole-genome sequencing are becoming increasingly routine approaches in
Mendelian disease diagnosis. Despite their success, the current diagnostic rate
for genomic analyses across a variety of rare diseases is approximately 25 to
50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA
seq)] as a complementary diagnostic tool in a cohort of 50 patients with
genetically undiagnosed rare muscle disorders. We describe an integrated approach
to analyze patient muscle RNA-seq, leveraging an analysis framework focused on
the detection of transcript-level changes that are unique to the patient compared
to more than 180 control skeletal muscle samples. We demonstrate the power of RNA
seq to validate candidate splice-disrupting mutations and to identify splice
altering variants in both exonic and deep intronic regions, yielding an overall
diagnosis rate of 35%. We also report the discovery of a highly recurrent de novo
intronic mutation in COL6A1 that results in a dominantly acting splice-gain
event, disrupting the critical glycine repeat motif of the triple helical domain.
We identify this pathogenic variant in a total of 27 genetically unsolved
patients in an external collagen VI-like dystrophy cohort, thus explaining
approximately 25% of patients clinically suggestive of having collagen VI
dystrophy in whom prior genetic analysis is negative. Overall, this study
represents a large systematic application of transcriptome sequencing to rare
disease diagnosis and highlights its utility for the detection and interpretation
of variants missed by current standard diagnostic approaches.
PMID- 28424334
TI - Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue
defective wound healing in mice.
AB - Excessive production of inflammatory chemokines can cause chronic inflammation
and thus impair cutaneous wound healing. Capturing chemokine signals using wound
dressing materials may offer powerful new treatment modalities for chronic
wounds. Here, a modular hydrogel based on end-functionalized star-shaped
polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG)
heparin was customized for maximal chemokine sequestration. The material is shown
to effectively scavenge the inflammatory chemokines MCP-1 (monocyte
chemoattractant protein-1), IL-8 (interleukin-8), and MIP-1alpha (macrophage
inflammatory protein-1alpha) and MIP-1beta (macrophage inflammatory protein
1beta) in wound fluids from patients suffering from chronic venous leg ulcers and
to reduce the migratory activity of human monocytes and polymorphonuclear
neutrophils. In an in vivo model of delayed wound healing (db/db mice), starPEG
GAG hydrogels outperformed the standard-of-care product Promogran with respect to
reduction of inflammation, as well as increased granulation tissue formation,
vascularization, and wound closure.
PMID- 28424336
TI - A Conversation with Karen Cichowski.
PMID- 28424337
TI - Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell
Invasion, Migration, and Metastasis.
AB - Cancer metastasis requires the invasion of tumor cells into the stroma and the
directed migration of tumor cells through the stroma toward the vasculature and
lymphatics where they can disseminate and colonize secondary organs. Physical and
biochemical gradients that form within the primary tumor tissue promote tumor
cell invasion and drive persistent migration toward blood vessels and the
lymphatics to facilitate tumor cell dissemination. These microenvironment cues
include hypoxia and pH gradients, gradients of soluble cues that induce
chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to
the concentration, organization, and stiffness of the extracellular matrix that
produce haptotactic, alignotactic, and durotactic gradients. These gradients form
through dynamic interactions between the tumor cells and the resident
fibroblasts, adipocytes, nerves, endothelial cells, infiltrating immune cells,
and mesenchymal stem cells. Malignant progression results from the integrated
response of the tumor to these extrinsic physical and chemical cues. Here, we
first describe how these physical and chemical gradients develop, and we discuss
their role in tumor progression. We then review assays to study these gradients.
We conclude with a discussion of clinical strategies used to detect and inhibit
these gradients in tumors and of new intervention opportunities. Clarifying the
role of these gradients in tumor evolution offers a unique approach to target
metastasis.
PMID- 28424338
TI - A Conversation with David Lyden.
PMID- 28424339
TI - Discovery of Double-Stranded Genomic DNA in Circulating Exosomes.
AB - It is becoming increasingly clear that small vesicles released from cells
(extracellular vesicles [EVs]) represent a heterogeneous population implicated in
cell-to-cell communication. The classifications and nomenclature of EVs are
evolving as enrichment strategies and specific characteristics are being
unraveled. At present, physical properties of EVs-namely, size, shape, and
density-are often used to identify subpopulations of EVs. A distinct group of
EVs, termed exosomes, largely defined by their small size (~40-150 nm) and
proposed subcellular origin, has been extensively studied in several aspects of
cancer biology. Exosomes are implicated in modulating behavior of cancer cells as
well as the immune and angiogenic responses in tumors, possibly contributing to
cancer progression locally and systemically. Most intriguingly, the nucleic acid
content of exosomes has been proposed to play a role in oncogenic transformation
and transfer of cancer-specific genome to promote cancer pathogenesis. Here, we
specifically focus on the discovery of exosomal DNA, studies related to the
origin of genomic DNA in exosomes, and its utility in cancer diagnosis and
disease monitoring.
PMID- 28424340
TI - A Conversation with Valerie Weaver.
PMID- 28424341
TI - Alterations in Three-Dimensional Organization of the Cancer Genome and Epigenome.
AB - The structural and functional basis of the genome is provided by the three
dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer
elements and promoter regions are brought into close spatial proximity to ensure
proper, cell type-specific gene expression. In cancer, genetic and epigenetic
processes can deregulate the transcriptional program. To investigate whether the
3D chromatin state is also disrupted in cancer we performed Hi-C chromosome
conformation sequencing in normal and prostate cancer cells and compared the
chromatin interaction maps with changes to the genome and epigenome. Notably, we
find that additional topologically associated domain (TAD) boundaries are formed
in cancer cells resulting in smaller TADs and altered gene expression profiles.
The new TAD boundaries are commonly associated with copy-number changes observed
in the cancer genome. We also identified new cancer-specific chromatin loops
within TADs that are enriched for enhancers and promoters. Finally, we find that
many of the long-range epigenetically silenced (LRES) and long-range
epigenetically active (LREA) regions in cancer are characterized by differential
chromatin interactions. Together our data provide a new insight into charting
alterations in higher-order structure and the relationship with genetic,
epigenetic, and transcriptional changes across the cancer genome.
PMID- 28424342
TI - Individual variation in local interaction rules can explain emergent patterns of
spatial organization in wild baboons.
AB - Researchers have long noted that individuals occupy consistent spatial positions
within animal groups. However, an individual's position depends not only on its
own behaviour, but also on the behaviour of others. Theoretical models of
collective motion suggest that global patterns of spatial assortment can arise
from individual variation in local interaction rules. However, this prediction
remains untested. Using high-resolution GPS tracking of members of a wild baboon
troop, we identify consistent inter-individual differences in within-group
spatial positioning. We then apply an algorithm that identifies what number of
conspecific group members best predicts the future location of each individual
(we call this the individual's neighbourhood size) while the troop is moving. We
find clear variation in the most predictive neighbourhood size, and this
variation relates to individuals' propensity to be found near the centre of their
group. Using simulations, we show that having different neighbourhood sizes is a
simple candidate mechanism capable of linking variation in local individual
interaction rules-in this case how many conspecifics an individual interacts with
to global patterns of spatial organization, consistent with the patterns we
observe in wild primates and a range of other organisms.
PMID- 28424343
TI - Interactive effects of temperature, food and skeletal mineralogy mediate
biological responses to ocean acidification in a widely distributed bryozoan.
AB - Marine invertebrates with skeletons made of high-magnesium calcite may be
especially susceptible to ocean acidification (OA) due to the elevated solubility
of this form of calcium carbonate. However, skeletal composition can vary
plastically within some species, and it is largely unknown how concurrent changes
in multiple oceanographic parameters will interact to affect skeletal mineralogy,
growth and vulnerability to future OA. We explored these interactive effects by
culturing genetic clones of the bryozoan Jellyella tuberculata (formerly
Membranipora tuberculata) under factorial combinations of dissolved carbon
dioxide (CO2), temperature and food concentrations. High CO2 and cold temperature
induced degeneration of zooids in colonies. However, colonies still maintained
high growth efficiencies under these adverse conditions, indicating a
compensatory trade-off whereby colonies degenerate more zooids under stress,
redirecting energy to the growth and maintenance of new zooids. Low-food
concentration and elevated temperatures also had interactive effects on skeletal
mineralogy, resulting in skeletal calcite with higher concentrations of
magnesium, which readily dissolved under high CO2 For taxa that weakly regulate
skeletal magnesium concentration, skeletal dissolution may be a more widespread
phenomenon than is currently documented and is a growing concern as oceans
continue to warm and acidify.
PMID- 28424344
TI - Mutualistic cleaner fish maintains high escape performance despite privileged
relationship with predators.
AB - Predatory reef fishes regularly visit mutualistic cleaner fish (Labroides
dimidiatus) to get their ectoparasites removed but show no interest in eating
them. The concept of compensated trait loss posits that characters can be lost if
a mutualistic relationship reduces the need for a given trait. Thus, selective
pressures on escape performance might have relaxed in L. dimidiatus due to its
privileged relationship with predators. However, the cost of failing to escape a
predatory strike is extreme even if predation events on cleaners are
exceptionally rare. Additionally, cleaners must escape from non-predatory clients
that regularly punish them for eating mucus instead of parasites. Therefore,
strong escape capabilities might instead be maintained in cleaner fish because
they must be able to flee when in close proximity to predators or dissatisfied
clients. We compared the fast-start escape performance of L. dimidiatus with that
of five closely related wrasse species and found that the mutualistic
relationship that cleaners entertain with predators has not led to reduced escape
performance. Instead, conflicts in cleaning interactions appear to have
maintained selective pressures on this trait, suggesting that compensated trait
loss might only evolve in cases of high interdependence between mutualistic
partners that are not tempted to cheat.
PMID- 28424345
TI - Floaters may buffer the extinction risk of small populations: an empirical
assessment.
AB - The high extinction risk of small populations is commonly explained by reductions
in fecundity and breeder survival associated with demographic and environmental
stochasticity. However, ecological theory suggests that population extinctions
may also arise from reductions in the number of floaters able to replace the lost
breeders. This can be particularly plausible under harsh fragmentation scenarios,
where species must survive as small populations subjected to severe effects of
stochasticity. Using a woodpecker study in fragmented habitats (2004-2016), we
provide here empirical support for the largely neglected hypothesis that floaters
buffer population extirpation risks. After controlling for population size, patch
size and the intrinsic quality of habitat, populations in patches with floaters
had a lower extinction probability than populations in patches without floaters
(0.013 versus 0.131). Floaters, which often replace the lost breeders, were less
likely to occur in small and low-quality patches, showing that population
extirpations may arise from unnoticed reductions in floater numbers in poor
quality habitats. We argue that adequate pools of the typically overlooked
floaters may buffer extirpation risks by reducing the detrimental impacts of
demographic and environmental stochasticity. However, unravelling the influence
of floaters in buffering stochastic effects and promoting population stability
require additional studies in an ample array of species and stochastic scenarios.
PMID- 28424346
TI - The 'male escape hypothesis': sex-biased metamorphosis in response to climatic
drivers in a facultatively paedomorphic amphibian.
AB - Paedomorphosis is a major evolutionary process that bypasses metamorphosis and
allows reproduction in larvae. In newts and salamanders, it can be facultative
with paedomorphs retaining gills and metamorphs dispersing. The evolution of
these developmental processes is thought to have been driven by the costs and
benefits of inhabiting aquatic versus terrestrial habitats. In this context, we
aimed at testing the hypothesis that climatic drivers affect phenotypic
transition and the difference across sexes because sex-ratio is biased in natural
populations. Through a replicated laboratory experiment, we showed that
paedomorphic palmate newts (Lissotriton helveticus) metamorphosed at a higher
frequency when water availability decreased and metamorphosed earlier when
temperature increased in these conditions. All responses were sex-biased, and
males were more prone to change phenotype than females. Our work shows how
climatic variables can affect facultative paedomorphosis and support theoretical
models predicting life on land instead of in water. Moreover, because males
metamorphose and leave water more often and earlier than females, these results,
for the first time, give an experimental explanation for the rarity of male
paedomorphosis (the 'male escape hypothesis') and suggest the importance of sex
in the evolution of paedomorphosis versus metamorphosis.
PMID- 28424347
TI - Long-term fitness consequences of early environment in a long-lived ungulate.
AB - Cohort effects can be a major source of heterogeneity and play an important role
in population dynamics. Silver-spoon effects, when environmental quality at birth
improves future performance regardless of the adult environment, can induce
strong lagged responses on population growth. Alternatively, the external
predictive adaptive response (PAR) hypothesis predicts that organisms will adjust
their developmental trajectory and physiology during early life in anticipation
of expected adult conditions but has rarely been assessed in wild species. We
used over 40 years of detailed individual monitoring of bighorn ewes (Ovis
canadensis) to quantify long-term cohort effects on survival and reproduction. We
then tested both the silver-spoon and the PAR hypotheses. Cohort effects involved
a strong interaction between birth and current environments: reproduction and
survival were lowest for ewes that were born and lived at high population
densities. This interaction, however, does not support the PAR hypothesis because
individuals with matching high-density birth and adult environments had reduced
fitness. Instead, individuals born at high density had overall lower lifetime
fitness suggesting a silver-spoon effect. Early-life conditions can induce long
term changes in fitness components, and their effects on cohort fitness vary
according to adult environment.
PMID- 28424348
TI - Tobacco: a threat to development?
PMID- 28424349
TI - Worldwide news and comment.
PMID- 28424350
TI - Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the
ventral tegmental area and reduction of transcription factor orthodenticle
homeobox 2 expression.
AB - Homozygous tau knockout (Mapt-/-) mice develop age-dependent dopaminergic (DA)
neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA),
supporting an important function of tau in maintaining the survival of midbrain
dopaminergic neurons (mDANs) during aging. However, it remains to be determined
whether the microtubule-associated protein tau regulates the differentiation and
survival of mDANs during embryonic developmental stages. Here, we show that tau
haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt+/-) pups, but not a
complete loss of tau in the Mapt-/- littermates, led to a significant reduction
of DA neurons in the VTA. This selective loss of DA neurons correlated with a
similar reduction in orthodenticle homeobox 2 (Otx2), which is restricted to VTA
neurons at the postmitotic stage and selectively controls the neurogenesis and
survival of specific neuronal subtypes of VTA. Moreover, the prenatal
developmental cell death in the Mapt+/- VTA specifically increased, and the
expression of microtubule-associated protein (MAP)-1A was significantly up
regulated in the P0 Mapt-/- , but not the Mapt+/- , pups. These results suggest
that tau haploinsufficiency, without the compensation effect of MAP1A, induces
reduction of Otx2 expression, increases prenatal cell death, and accordingly
leads to selective loss of VTA DA neurons in the early postnatal stage. Our
findings highlight the impact of tau haploinsufficiency on the survival of mDANs
and indicate that tau may participate in midbrain development in a dose-dependent
way.-Zheng, M., Jiao, L., Tang, X., Xiang, X., Wan, X., Yan, Y., Li, X., Zhang,
G., Li, Y., Jiang, B., Cai, H., Lin, X. Tau haploinsufficiency causes prenatal
loss of dopaminergic neurons in the ventral tegmental area and reduction of
transcription factor orthodenticle homeobox 2 expression.
PMID- 28424351
TI - miR-191 suppresses angiogenesis by activation of NF-kappaB signaling.
AB - MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes.
However, the function of most miRNAs in angiogenesis remains elusive. In this
study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel
development. Transfection of human dermal microvascular endothelial cells with
miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube
formation. Moreover, vascular sprouting of miR-191m-transfected mouse aortic
rings was significantly reduced when compared with controls. Transfection with
miR-191 inhibitor (miR-191i) induced proangiogenic effects. The anti- and
proangiogenic activities of miR-191m and -191i were further demonstrated in vivo
Additional molecular biologic analyses revealed that miR-191m activates NF-kappaB
signaling by up-regulating the mRNA expression of p65. miR-191 also increased the
mRNA levels of the antiangiogenic factors p21 and tissue inhibitor of
metalloproteinase-1 and reduced the expression of the proangiogenic factors eNOS
and matrix metalloproteinase-1 and -9. Blockade of NF-kappaB activation with Bay
11-7082 reversed the antiangiogenic effects of miR-191m. These findings indicate
that miR-191 effectively suppresses angiogenesis by activation of the NF-kappaB
signaling pathway.-Gu, Y., Ampofo, E., Menger, M. D., Laschke, M. W. miR-191
suppresses angiogenesis by activation of NF-kappaB signaling.
PMID- 28424352
TI - Chromatin module inference on cellular trajectories identifies key transition
points and poised epigenetic states in diverse developmental processes.
AB - Changes in chromatin state play important roles in cell fate transitions. Current
computational approaches to analyze chromatin modifications across multiple cell
types do not model how the cell types are related on a lineage or over time. To
overcome this limitation, we developed a method called Chromatin Module INference
on Trees (CMINT), a probabilistic clustering approach to systematically capture
chromatin state dynamics across multiple cell types. Compared to existing
approaches, CMINT can handle complex lineage topologies, capture higher quality
clusters, and reliably detect chromatin transitions between cell types. We
applied CMINT to gain novel insights in two complex processes: reprogramming to
induced pluripotent stem cells (iPSCs) and hematopoiesis. In reprogramming,
chromatin changes could occur without large gene expression changes, different
combinations of activating marks were associated with specific reprogramming
factors, there was an order of acquisition of chromatin marks at pluripotency
loci, and multivalent states (comprising previously undetermined combinations of
activating and repressive histone modifications) were enriched for CTCF. In the
hematopoietic system, we defined critical decision points in the lineage tree,
identified regulatory elements that were enriched in cell-type-specific regions,
and found that the underlying chromatin state was achieved by specific erasure of
preexisting chromatin marks in the precursor cell or by de novo assembly. Our
method provides a systematic approach to model the dynamics of chromatin state to
provide novel insights into the relationships among cell types in diverse cell
fate specification processes.
PMID- 28424353
TI - Constrained release of lamina-associated enhancers and genes from the nuclear
envelope during T-cell activation facilitates their association in chromosome
compartments.
AB - The 3D organization of the genome changes concomitantly with expression changes
during hematopoiesis and immune activation. Studies have focused either on lamina
associated domains (LADs) or on topologically associated domains (TADs), defined
by preferential local chromatin interactions, and chromosome compartments,
defined as higher-order interactions between TADs sharing functionally similar
states. However, few studies have investigated how these affect one another. To
address this, we mapped LADs using Lamin B1-DamID during Jurkat T-cell
activation, finding significant genome reorganization at the nuclear periphery
dominated by release of loci frequently important for T-cell function. To assess
how these changes at the nuclear periphery influence wider genome organization,
our DamID data sets were contrasted with TADs and compartments. Features of
specific repositioning events were then tested by fluorescence in situ
hybridization during T-cell activation. First, considerable overlap between TADs
and LADs was observed with the TAD repositioning as a unit. Second, A1 and A2
subcompartments are segregated in 3D space through differences in proximity to
LADs along chromosomes. Third, genes and a putative enhancer in LADs that were
released from the periphery during T-cell activation became preferentially
associated with A2 subcompartments and were constrained to the relative proximity
of the lamina. Thus, lamina associations influence internal nuclear organization,
and changes in LADs during T-cell activation may provide an important additional
mode of gene regulation.
PMID- 28424356
TI - The direct and indirect influence of own mother's milk on bronchopulmonary
dysplasia and costs.
PMID- 28424354
TI - Less effective selection leads to larger genomes.
AB - The evolutionary origin of the striking genome size variations found in
eukaryotes remains enigmatic. The effective size of populations, by controlling
selection efficacy, is expected to be a key parameter underlying genome size
evolution. However, this hypothesis has proved difficult to investigate using
empirical data sets. Here, we tested this hypothesis using 22 de novo
transcriptomes and low-coverage genomes of asellid isopods, which represent 11
independent habitat shifts from surface water to resource-poor groundwater. We
show that these habitat shifts are associated with higher transcriptome-wide
[Formula: see text] After ruling out the role of positive selection and
pseudogenization, we show that these transcriptome-wide [Formula: see text]
increases are the consequence of a reduction in selection efficacy imposed by the
smaller effective population size of subterranean species. This reduction is
paralleled by an important increase in genome size (25% increase on average), an
increase also confirmed in subterranean decapods and mollusks. We also control
for an adaptive impact of genome size on life history traits but find no
correlation between body size, or growth rate, and genome size. We show instead
that the independent increases in genome size measured in subterranean isopods
are the direct consequence of increasing invasion rates by repeat elements, which
are less efficiently purged out by purifying selection. Contrary to selection
efficacy, polymorphism is not correlated to genome size. We propose that recent
demographic fluctuations and the difficulty of observing polymorphism variation
in polymorphism-poor species can obfuscate the link between effective population
size and genome size when polymorphism data are used alone.
PMID- 28424357
TI - Thin-for-gestational age infants are at increased risk of neurodevelopmental
delay at 2 years.
AB - BACKGROUND: Infants born small-for-gestational age (SGA) are at increased risk of
developmental difficulties. Identifying those most at risk is challenging. We
examined the effect of neonatal body composition and customised birthweight
centiles on neurocognitive and behavioural outcomes at age 2. STUDY DESIGN:
Prospective cohort study of term infants from the Cork BASELINE Birth Cohort
Study classified into the following exposure groups: a birth weight <10th
customised centile (SGA, n=51); body fat percentage at birth <10th centile (thin
for-gestational age (TGA, n=51)) or both SGA and TGA infants (small- and thin-for
gestational age (STGA), n=13). The SGA, TGA and STGA groups were compared with a
reference (unexposed) group of appropriate-for-gestational age (AGA, n=189)
infants. Outcome was assessed at 24 months using the Bayley Scales of Infant
Development Version III and the Child Behaviour Checklist. RESULTS: Outcomes in
the SGA infants did not differ significantly from the AGA group. TGA infants had
significantly lower scores across all three domains, with a 0.35, 0.38 and 0.41
SD reduction in language, cognitive and motor scale scores, respectively. STGA
infants had poorer cognitive outcome with a median cognitive scale score of 90
(IQR 85-95) compared with 95 (IQR 90-100) in the AGA reference group, p=0.005.
The adjusted OR of developmental delay at 2 years was 5.00 (95% CI 1.46 to 17.13,
p=0.010) in the STGA group. CONCLUSION: TGA infants, in particular those born
STGA, are at increased risk of developmental delay at 2 years compared with the
AGA infants.
PMID- 28424358
TI - Ultrasound assessment of umbilical venous catheter migration in preterm infants:
a prospective study.
AB - OBJECTIVES: To evaluate the umbilical venous catheter (UVC) tip position by
ultrasound and compare it with standard radiograph findings and to examine the
catheter tip migration rates during the first week of life. DESIGN: Prospective
observational study of inborn preterm infants who had an UVC placed and its
position radiographically confirmed. The first ultrasound was done on UVC
placement at median (IQR) age of 2 hours (1-4) and follow-up scans at a median
(IQR) age of 34 hours (27-44 hours), 77 hours (70-94 hours) and 6 days (5-7 days)
after insertion. Catheter tip was considered in optimum position if tip was lying
in the inferior vena cava up to the right atrium opening. RESULTS: We studied 65
infants at a mean (+/-SD) gestational age and birth weight of 26.4 (+/-2.1) weeks
and 808 (+/-289) g, respectively. Ultrasound confirmed optimum position of UVC
tip in 25/65 (38.5%) infants. Majority (38/40) of the malpositioned catheters
were located inside the heart with 15 reaching the left atrium. Catheter tip
migration occurred in 29 of 58 infants (50%) at any time during the first week.
The proportions of UVC migration were found to be 17%, 31% and 29% on subsequent
ultrasound with a trend to outward movement over time. CONCLUSION: UVC tip
localisation by standard radiography is very imprecise, and catheter tip
migration occurs in a significant proportion of infants during first weeks of
age. We suggest ultrasound as the best modality to assist localisation and follow
up of UVC tip in preterm infants.
PMID- 28424359
TI - Effects of combined tiotropium/olodaterol on inspiratory capacity and exercise
endurance in COPD.
AB - Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and
2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and
exercise endurance time in patients with moderate to severe chronic obstructive
pulmonary disease.For each patient, four of five treatments were administered
once daily for 6 weeks, with a 21-day washout between treatments:
tiotropium/olodaterol 2.5/5 ug or 5/5 ug, tiotropium 5 ug, olodaterol 5 ug or
placebo, all via the Respimat inhaler. Primary outcomes were inspiratory capacity
prior to exercise and exercise endurance time during constant work-rate cycle
ergometry to symptom limitation at 75% of peak incremental work rate after 6
weeks (2 h post-dose).295 and 291 patients were treated in MORACTO 1 and 2,
respectively. Tiotropium/olodaterol 2.5/5 and 5/5 ug provided significant
improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001),
and significant improvements in exercise endurance time versus placebo
(p<0.0001). Intensity of breathing discomfort was reduced following both doses of
tiotropium/olodaterol versus placebo (p<0.0001).Once-daily tiotropium/olodaterol
yielded improvements in lung hyperinflation versus placebo and statistically
significant improvements versus monotherapies. Tiotropium/olodaterol also showed
improvements in dyspnoea and exercise tolerance versus placebo but not
consistently versus monotherapies.
PMID- 28424360
TI - Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance
through adipose tissue inflammation.
AB - Obstructive sleep apnoea (OSA) is increasingly associated with insulin
resistance. The underlying pathophysiology remains unclear but intermittent
hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose
tissue has been hypothesised to play a key role.We tested this hypothesis
employing a comprehensive translational approach using a murine IH model of lean
and diet-induced obese mice, an innovative IH system for cell cultures and a
tightly controlled patient cohort.IH led to the development of insulin resistance
in mice, corrected for the degree of obesity, and reduced insulin-mediated
glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin
signalling pathway and downregulation of insulin-receptor substrate-1 mRNA.
Providing mechanistic insight, IH induced a pro-inflammatory phenotype of
visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation
correlating with the severity of insulin resistance. Complimentary in vitro
analysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages.
In subjects without comorbidities (n=186), OSA was independently associated with
insulin resistance. Furthermore, we found an independent correlation of OSA
severity with the M1 macrophage inflammatory marker sCD163.This study provides
evidence that IH induces a pro-inflammatory phenotype of the adipose tissue,
which may be a crucial link between OSA and the development of insulin
resistance.
PMID- 28424361
TI - Computed tomographic findings in subjects who died from respiratory disease in
the National Lung Screening Trial.
AB - We evaluated the prevalence of significant lung abnormalities on computed
tomography (CT) in patients who died from a respiratory illness other than lung
cancer in the National Lung Screening Trial (NLST).In this retrospective case
control study, NLST participants in the CT arm who died of respiratory illness
other than lung cancer were matched for age, sex, pack-years and smoking status
to a surviving control. A chest radiologist and a radiology resident blinded to
the outcome independently scored baseline CT scans visually and qualitatively for
the presence of emphysema, airway wall thickening and fibrotic lung disease. The
prevalence of CT abnormalities was compared between cases and controls by using
chi-squared tests.In total, 167 participants died from a respiratory cause other
than lung cancer. The prevalence of severe emphysema, airway wall thickening and
fibrotic lung disease were 28.7% versus 4.8%, 26.9% versus 13.2% and 18.6% versus
0.5% in cases and controls, respectively. Radiological findings were
significantly more prevalent in deaths compared with controls (all p<0.001).CT
diagnosed severe emphysema, airway wall thickening and fibrosis were much more
common in NLST participants who died from respiratory disease, and CT may provide
an additional means of identifying these diseases.
PMID- 28424362
TI - Effect of the cooling sensation induced by olfactory stimulation by L-menthol on
dyspnoea: a pilot study.
PMID- 28424363
TI - Yield of tuberculosis screening in asylum-seekers by country of origin: analysis
of screening data in a German federal state (2002-2015).
PMID- 28424364
TI - Time to take CT screening to the next level?
PMID- 28424365
TI - Language discordance between tuberculosis patients and healthcare providers
challenging universal access.
PMID- 28424366
TI - Sleep apnoea, insulin resistance and diabetes: the first step is in the fat.
PMID- 28424367
TI - Chronic obstructive pulmonary disease: inhale deeply and start to exercise.
PMID- 28424368
TI - Spatial intensity distribution analysis quantifies the extent and regulation of
homodimerization of the secretin receptor.
AB - Previous studies have indicated that the G-protein-coupled secretin receptor is
present as a homodimer, organized through symmetrical contacts in transmembrane
domain IV, and that receptor dimerization is critical for high-potency signalling
by secretin. However, whether all of the receptor exists in the dimeric form or
if this is regulated is unclear. We used measures of quantal brightness of the
secretin receptor tagged with monomeric enhanced green fluorescent protein
(mEGFP) and spatial intensity distribution analysis to assess this. Calibration
using cells expressing plasma membrane-anchored forms of mEGFP initially allowed
us to demonstrate that the epidermal growth factor receptor is predominantly
monomeric in the absence of ligand and while wild-type receptor was rapidly
converted into a dimeric form by ligand, a mutated form of this receptor remained
monomeric. Equivalent studies showed that, at moderate expression levels, the
secretin receptor exists as a mixture of monomeric and dimeric forms, with little
evidence of higher-order complexity. However, sodium butyrate-induced up
regulation of the receptor resulted in a shift from monomeric towards oligomeric
organization. In contrast, a form of the secretin receptor containing a pair of
mutations on the lipid-facing side of transmembrane domain IV was almost entirely
monomeric. Down-regulation of the secretin receptor-interacting G-protein Galphas
did not alter receptor organization, indicating that dimerization is defined
specifically by direct protein-protein interactions between copies of the
receptor polypeptide, while short-term treatment with secretin had no effect on
organization of the wild-type receptor but increased the dimeric proportion of
the mutated receptor variant.
PMID- 28424369
TI - Dietary capsaicin and its anti-obesity potency: from mechanism to clinical
implications.
AB - Obesity is a growing public health problem, which has now been considered as a
pandemic non-communicable disease. However, the efficacy of several approaches
for weight loss is limited and variable. Thus, alternative anti-obesity
treatments are urgently warranted, which should be effective, safe, and widely
available. Active compounds isolated from herbs are similar with the practice of
Traditional Chinese Medicine, which has a holistic approach that can target to
several organs and tissues in the whole body. Capsaicin, a major active compound
from chili peppers, has been clearly demonstrated for its numerous beneficial
roles in health. In this review, we will focus on the less highlighted aspect, in
particular how dietary chili peppers and capsaicin consumption reduce body weight
and its potential mechanisms of its anti-obesity effects. With the widespread
pandemic of overweight and obesity, the development of more strategies for the
treatment of obesity is urgent. Therefore, a better understanding of the role and
mechanism of dietary capsaicin consumption and metabolic health can provide
critical implications for the early prevention and treatment of obesity.
PMID- 28424370
TI - Multi-site binding of epigallocatechin gallate to human serum albumin measured by
NMR and isothermal titration calorimetry.
AB - The affinity of epigallocatechin gallate (EGCG) for human serum albumin (HSA) was
measured in physiological conditions using NMR and isothermal titration
calorimetry (ITC). NMR estimated the Ka (self-dissociation constant) of EGCG as
50 mM. NMR showed two binding events: strong (n1=1.8 +/- 0.2; Kd1 =19 +/- 12 MUM)
and weak (n2~20; Kd2 =40 +/- 20 mM). ITC also showed two binding events: strong
(n1=2.5 +/- 0.03; Kd1 =21.6 +/- 4.0 MUM) and weak (n2=9 +/- 1; Kd2 =22 +/- 4 mM).
The two techniques are consistent, with an unexpectedly high number of bound
EGCG. The strong binding is consistent with binding in the two Sudlow pockets.
These results imply that almost all EGCG is transported in the blood bound to
albumin and explains the wide tissue distribution and chemical stability of EGCG
in vivo.
PMID- 28424371
TI - Comprehensive assessment of cavernosography with 320-row dynamic volume CT versus
conventional cavernosography in erectile dysfunction patients caused by venous
leakage.
AB - The present study aims to investigate and compare the diagnostic and prognostic
value of cavernosography with 320-row dynamic volume computed tomography (DVCT)
versus conventional cavernosography in men with erectile dysfunction (ED) caused
by venous leakage. A total of 174 patients diagnosed with ED were enrolled and
received cavernosography with 320-row DVCT (DVCT group) and conventional
cavernosography scans (control group) respectively. The diagnosis, complications,
and prognosis of patients were evaluated. The DVCT group provided high-resolution
images with less processing and testing time, as well as lowered radiological
agent and contrast agent compared with the control group. In the DVCT group, 89
patients who were diagnosed with venous ED had six various venous leakage, namely
superficial venous leakage, profundus venous leakage, the mixed type, cavernosal
venous leakage, crural venous leakage, and also venous leakage between the penis
and urethra cavernosum (9, 21, 32, 6, 18, and 3 cases respectively). Similarly,
74 patients out of the 81 who suffered from venous ED were classified to have
superficial venous leakage (11), profundus venous leakage (14), the mixed type
venous leakage (26), and middle venous leakage (23). Six out of 25 patients in
the DVCT group, had improvements in ED while the remaining 19 achieved full
erectile function recovery with no penile fibrosis and erectile pain.
Cavernosography with 320-row DVCT is a reliable system that can be used to
diagnose ED caused by venous leakage. This is especially useful in accurately
determining the type of venous and allows for a better prognosis and direction of
treatment.
PMID- 28424372
TI - Effects of drought stress on global gene expression profile in leaf and root
samples of Dongxiang wild rice (Oryza rufipogon).
AB - Drought is a serious constraint to rice production throughout the world, and
although Dongxiang wild rice (Oryza rufipogon, DXWR) possesses a high degree of
drought resistance, the underlying mechanisms of this trait remains unclear. In
the present study, cDNA libraries were constructed from the leaf and root tissues
of drought-stressed and untreated DXWR seedlings, and transcriptome sequencing
was performed with the goal of elucidating the molecular mechanisms involved in
drought-stress response. The results indicated that 11231 transcripts were
differentially expressed in the leaves (4040 up-regulated and 7191 down
regulated) and 7025 transcripts were differentially expressed in the roots (3097
up-regulated and 3928 down-regulated). Among these differentially expressed genes
(DEGs), the detection of many transcriptional factors and functional genes
demonstrated that multiple regulatory pathways were involved in drought
resistance. Meanwhile, the DEGs were also annotated with gene ontology (GO) terms
and key pathways via functional classification and Kyoto Encyclopedia of Gene and
Genomes (KEGG) pathway mapping, respectively. A set of the most interesting
candidate genes was then identified by combining the DEGs with previously
identified drought-resistant quantitative trait loci (QTL). The present work
provides abundant genomic information for functional dissection of the drought
resistance of DXWR, and findings will further help the current understanding of
the biological regulatory mechanisms of drought resistance in plants and
facilitate the breeding of new drought-resistant rice cultivars.
PMID- 28424373
TI - Statins, PCSK9 inhibitors and cholesterol homeostasis: a view from within the
hepatocyte.
AB - Statins and PCSK9 inhibitors dramatically lower plasma LDL levels and
dramatically increase LDL receptor number within hepatocyte cell membranes. It
seems self-evident that total clearance of LDL particles from plasma and total
delivery of cholesterol to the liver must increase in consequence. However, based
on the results of stable isotope tracer studies, this analysis demonstrates the
contrary to be the case. Statins do not change the production rate of LDL
particles. Accordingly, at steady state, the clearance rate cannot change.
Because LDL particles contain less cholesterol on statin therapy, the delivery of
cholesterol to the liver must, therefore, be reduced. PCSK9 inhibitors reduce the
production of LDL particles and this further reduces cholesterol delivery to the
liver. With both agents, a larger fraction of a smaller pool is removed per unit
time. These findings are inconsistent with the conventional model of cholesterol
homeostasis within the liver, but are consistent with a new model of regulation,
the multi-channel model, which postulates that different lipoprotein particles
enter the hepatocyte by different routes and have different metabolic fates
within the hepatocyte. The multi-channel model, but not the conventional model,
may explain how statins and PCSK9 inhibitors can produce sustained increases in
LDL receptor number.
PMID- 28424374
TI - Mechanisms of vascular disease in dementia: what does industry want to know?
AB - Despite recent advances in basic and clinical science, dementia remains an area
of high unmet medical need. The role of cerebrovascular mechanisms in the
pathogenesis and progression of cognitive and functional impairment in dementia
is being revived. In order to facilitate the development of therapeutic
approaches, it is critical that a number of fundamental elements are integrated
into research strategies investigating cerebrovascular pathologies as these will
maximize the opportunity of bringing medicines to patients in a timely manner.
PMID- 28424375
TI - Mitochondria: a central target for sex differences in pathologies.
AB - It is increasingly acknowledged that a sex and gender specificity affects the
occurrence, development, and consequence of a plethora of pathologies.
Mitochondria are considered as the powerhouse of the cell because they produce
the majority of energy-rich phosphate bonds in the form of adenosine tri
phosphate (ATP) but they also participate in many other functions like steroid
hormone synthesis, reactive oxygen species (ROS) production, ionic regulation,
and cell death. Adequate cellular energy supply and survival depend on
mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics,
and quality control via mitophagy. It appears that mitochondria are the place of
marked sexual dimorphism involving mainly oxidative capacities, calcium handling,
and resistance to oxidative stress. In turn, sex hormones regulate mitochondrial
function and biogenesis. Mutations in genes encoding mitochondrial proteins are
the origin of serious mitochondrial genetic diseases. Mitochondrial dysfunction
is also an important parameter for a large panel of pathologies including
neuromuscular disorders, encephalopathies, cardiovascular diseases (CVDs),
metabolic disorders, neuropathies, renal dysfunction etc. Many of these
pathologies present sex/gender specificity. Here we review the sexual dimorphism
of mitochondria from different tissues and how this dimorphism takes part in the
sex specificity of important pathologies mainly CVDs and neurological disorders.
PMID- 28424377
TI - Sex differences in micro- and macro-vascular complications of diabetes mellitus.
AB - Vascular complications are a leading cause of morbidity and mortality in both men
and women with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus, however the
prevalence, progression and pathophysiology of both microvascular (nephropathy,
neuropathy and retinopathy) and macrovascular [coronary heart disease (CHD),
myocardial infarction, peripheral arterial disease (PAD) and stroke] disease are
different in the two sexes. In general, men appear to be at a higher risk for
diabetic microvascular complications, while the consequences of macrovascular
complications may be greater in women. Interestingly, in the absence of diabetes,
women have a far lower risk of either micro- or macro-vascular disease compared
with men for much of their lifespan. Thus, the presence of diabetes confers
greater risk for vascular complications in women compared with men and some of
the potential reasons, including contribution of sex hormones and sex-specific
risk factors are discussed in this review. There is a growing body of evidence
that sex hormones play an important role in the regulation of cardiovascular
function. While estrogens are generally considered to be cardioprotective and
androgens detrimental to cardiovascular health, recent findings challenge these
assumptions and demonstrate diversity and complexity of sex hormone action on
target tissues, especially in the setting of diabetes. While some progress has
been made toward understanding the underlying mechanisms of sex differences in
the pathophysiology of diabetic vascular complications, many questions and
controversies remain. Future research leading to understanding of these
mechanisms may contribute to personalized- and sex-specific treatment for
diabetic micro- and macro-vascular disease.
PMID- 28424376
TI - SerpinC1/Antithrombin III in kidney-related diseases.
AB - The gene SerpinC1 encodes a serine protease inhibitor named antithrombin III
(ATIII). This protease demonstrates both anticoagulant and anti-inflammatory
action. ATIII is the most important coagulation factor inhibitor, and even minor
changes in ATIII can significantly alter the risk of thromboembolism. ATIII can
also suppress inflammation via a coagulation-dependent or -independent effect.
Moreover, apart from ATIII deficiency, ATIII and its gene SerpinC1 may also be
related to many diseases (e.g. hypertension, kidney diseases). The present review
summarizes how ATIII affects the progress of kidney disease and its mechanism.
Further studies are required to investigate how ATIII affects renal function and
the treatment.
PMID- 28424378
TI - [Recognition, care and prevention of suicidal behaviour in adults].
AB - : Suicide is a major public health problem everywhere in the world and in the WHO
European Region suicide accounts for over 120,000 deaths per year. 1. Recognition
and diagnosis: An underlying psychiatric disorder is present in up to 90% of
people who completed suicide. Comorbidity with depression, anxiety, substance
abuse and personality disorders is high. In order to achieve successful
prevention of suicidality, adequate diagnostic procedures and appropriate
treatment for the underlying disorder are essential. 2. Treatment and care: Acute
intervention should start immediately in order to keep the patient alive.
Existing evidence supports the efficacy of pharmacological treatment and
cognitive behavioural therapy (including dialectical behavior therapy and problem
solving therapy) in preventing suicidal behaviour. Some other psychological
treatments are promising, but the supporting evidence is currently insufficient.
Studies show that antidepressant and mood stabilizer treatments decrease the risk
for suicidality among responders in mood disorder patients. However, the risk of
suicidal behaviour in depressed patients treated with antidepressants exists
during the first 10-14 days of treatment, which requires careful monitoring.
Short-term supplementary medication with anxiolytics and hypnotics in the case of
anxiety and insomnia is recommended. Treatment with antidepressants of children
and adolescents should only be given under supervision of a specialist. Long-term
treatment with lithium has been shown to be very effective in preventing both
suicide and attempted suicide in patients with unipolar and bipolar depression.
Treatment with clozapine is effective in reducing suicidal behaviour in patients
with schizophrenia. Other atypical antipsychotics are promising but more evidence
is required. 3. Family and social support: The suicidal person should always be
motivated to involve family in the treatment. Psychosocial treatment and support
is recommended, as the majority of suicidal patients have problems with
relationships, work, school and lack functioning social networks. 4. SAFETY: A
secure home, public and hospital environment, without access to suicidal means is
a necessary strategy in suicide prevention. Each treatment option, prescription
of medication and discharge of the patient from hospital should be carefully
evaluated against the involved risks. 5. Education of treatment team: Training of
general practitioners is effective in the prevention of suicide. It improves
treatment of depression and anxiety, quality of the provided care and attitudes
towards suicide. Continuous training including discussions about ethical and
legal issues is necessary for psychiatrists and other mental health
professionals. Multidisciplinary treatment teams including psychiatrist and other
professionals such as psychologist, social worker, and occupational therapist are
always preferable, as integration of pharmacological, psychological and social
rehabilitation is recommended especially for patients with chronic suicidality.
6. Public aspects: Not only the health care workers are responsible for suicide
prevention. All members of our society (including community/political leaders as
well as religious and civil organizations) have their own task with more or less
competence and responsibility.
PMID- 28424379
TI - [Risk factors of eating disorders in the narratives of fashion models].
AB - INTRODUCTION: The risk of eating disorders is high in populations who are exposed
to slimness ideal, so among fashion models. The present qualitative study
evaluates the risk factors of eating disorders in a group of fashion models with
semistructured interview. Moreover, the aim of the study was to examine the
impact of professional requirements on the health of models. METHODS: The study
group was internationally heterogeneous. The models were involved by personal
professional relationship. A semistructured questionnaire was used by e-mail
containing anthropometric data and different aspects of the model profession.
RESULTS: 29 female and three male models, three agents, two designers, three
fotographers, one personal trainer and one stylist answered the questionnaire.
Transient bulimic symptoms were reported by six female models (21%). Moreover,
five female models fulfilled the DSM-5 criteria of anorexia nervosa or bulimia
nervosa. Four of them were anorexic (body mass index: 13.9-15.3), one was
bulimic. The symptoms of three persons began before the model career, those of
two models after it. 17 models reported that the model profession intensively
increased the bodily preoccupations. CONCLUSION: The study corroborates the
effect of the model profession on the increase of the risk for eating disorders.
In the case of the models, whose eating disorder began after stepping into the
model profession, the role of the representants of the fashion industry can be
suggested as a form of psychological abuse. As the models or in the case of
underages their parents accepted the strong requirement of slimness, an
unconscious collusion is probable. Our date highlight the health impact of
cultural ideals, and call the attention to prevention strategies.
PMID- 28424380
TI - [Schizotypy: detachment or magical fusion].
AB - Nowadays, both in the clinical population, and in general communities, we tend to
encounter an increasing number of personality disorder patients, whose social
adjustment, partnerships and efficient life management is made difficult by the
disorder. The ideas of borderline personality disorder patients, who fluctuate
between farfetched expectations and fears of their selves being demolished,
schizoid patients, who close their selves in their own alienating prison,
avoidant patients, who try to escape difficulties, which would enhance their self
esteem, OCD patients, who build their own mythic superstitious world, and
antisocial patients who tend to ignore and aggressively override others'
interests are all important in the development of cultures with insecure
identities. Taking into consideration the symptoms enlisted in the diagnostic
system of DSM-5, it is the task of experts of cultural anthropology, psychology,
psychopathology and cognitive neuroscience to explore the referring ways of
personality development, relationships and of conflict management.
Notwithstanding, avoiding the psychopathological terminology, rather pointing at
population characteristics, we need to identify personal functionings of the
general features of perception, cognition and world views, which in the long run,
may modify personal developmental possibilities, individual approaches to
information technology, and emotional, family or professional motivations. Based
on the respective literature and clinical experience, below we intend to explore
the different aspects of schizotypy, which contribute to the formation of
schizoid personality disorder. We analyze the interrelations of avoiding
relationships and empathy toward relationship building.
PMID- 28424381
TI - [The relationship between physical activity and executive functions among
children with attention-deficit hyperactivity disorder].
AB - The connection between physical activity and executive functions has recently
started to emerge as a new focus of research within the field of attention
deficit-hyperactivity-disorder (ADHD). In the present paper we summarise the
major findings of these studies concentrating specifically on paediatric
population. We present the results of six studies that focus on the connection
between acute physical activity and executive functions and seven others that
examine the relationship between chronic physical activity and executive
functions in children with ADHD. The forms of physical activity as well as the
executive functions measured show great variability within the studies reviewed.
Four out of the six studies using acute physical activity, and all of the studies
using chronic physical activity have found evidence of improvement in at least
some areas of executive functioning. Further studies are needed to confirm the
applicability of acute as well as chronic physical activity as a potential
additional treatment in ADHD. Also, clarifying the optimal parameters (i.e. type,
intensity, duration, frequency) of physical activity while also taking into
consideration the individual characteristics (i.e. gender, age, physical
fittness, type of ADHD, comorbidity) of children with ADHD could be important
aims of future studies.
PMID- 28424382
TI - [Near miss outcomes in gambling games].
AB - BACKGROUND: Games of chance operate with an intermittent reinforcement schedule
in which the number of games takes the player to win differ in each turn thus
they can not predict when the next positive reinforcement arrives. The near miss
outcome (close to winning but actually a losing outcome) can be interpreted as a
secondary (built in) reinforcement within variable ratio reinforcement schedule
that presumably contribute to the development and maintanance of gambling
addiction. METHODS: The aim of this publication would be to introduce near miss
outcomes and to summarize and critically analyze literature connected to this
issue.We searched internet datebases using word "near miss" and analyse articles
focusing on gambling games. RESULTS: Based on numerous authors' results a near
miss rate set at around 30% increases the desire to continue playing among
gamblers and players who have no former gambling experience as well. CONCLUSIONS:
Some studies have demonstrated that this effect might be related to the extent
the player has the situation under control during the gambling session. The
hypothetical inhibiting effect of a 45% near miss ratio has not yet been proven.
Neurobiological researches show middle-cerebral activity during near miss
outcomes furthermore similar physiological patterns have been discovered
following a near miss and winning outcomes. Regarding the connection between
intrapsychic variables (cognitive and personality factors) and near misses there
are very few studies. The fact that different authors interpret near miss
outcomes differently even when studying the same game leads to problems in
interpreting their results. It follows from the foregoing empirical results that
near miss outcomes contribute to the development and maintanance of pathological
gambling but we have little information on the factors implementing this effect.
PMID- 28424383
TI - [Long-acting injection - four-times-a-year. Review of the 3-monthly paliperidone
palmitate injection].
AB - Continuous maintenance antipsychotic treatment is one of the most important
factor in the long-term course of schizophrenia. Among the therapeutic options
available today, the long-acting injectable antipsychotics are those that are
able to efficiently provide an optimal treatment strategy required for continuous
maintenance treatment. Three-monthly paliperidone palmitate (TREVICTA) is an
important milestone in this therapeutic approach, since it is the first and only
antipsychotic treatment for patients with schizophrenia, which provides the
yearly maintenance therapeutic dose by four injections. Clinical studies have
shown that compared to the placebo, TREVICTA significantly delays time to
relapse, reduces relapse rate, and its effect is equivalent to the well-known
monthly paliperidone palmitate. Data on safety have revealed that TREVICTA was
well tolerated and safe, and the rare side effects were consistent with that of
paliperidone previously described. In conclusion, TREVICTA is a new and unique
treatment option for patients who respond well to paliperidone treatment.
PMID- 28424384
TI - Minor physical anomalies and dermatoglyphic signs in affective disorders: A
systematic review.
AB - The increased prevalence of minor physical anomalies (MPAs) and the abnormalities
of dermatoglyphic patterns may be physical manifestations of neurodevelopmental
disruption in affective disorders. This paper aims to review the current state of
knowledge on the frequency of MPAs and dermatoglyphic abnormalities in mood
disorders. A MEDLINE, PsychInfo and Web of Science search was carried out to
collect all publications on the frequency of MPAs and on dermatoglyphic traits in
bipolar disorder and unipolar depression. 24 studies on MPAs, 19 on
dermatoglyphics, and 5 dealing with both were found with discrepant findings. The
relative contribution of neurodevelopmental retardation to the aetiology of
affective disorders remains undetermined, the field is open for further research.
Increased recognition of neurodevelopmental processes in the origin of affective
disorders may allow for earlier and more effective intervention and prevention.
PMID- 28424385
TI - [Korbinian Brodmann's Scientific Profile, and Academic Works].
AB - Brodmann's map is one of the best known maps of the human cerebral cortex.
However, Korbinian Brodmann's 1909 monograph, containing the first map, has not
been widely read by neurologists. Following the publication of the first map,
Brodmann reproduced the map in 1910, and again in 1914, with several important
differences. The latter map is also characterized by the exclusion of Brodmann
area numbers, "12-16, and 48-51;" contrastingry numbers "1-52" have been
described in the animal brain. Here, we provide a detailed explanation of the
versions of Brodmann's maps, and review his academic profile and works.
PMID- 28424386
TI - [Touch: Brodmann Areas 3, 1, and 2].
AB - A brief history of cytoarchitectonic studies of Brodmann areas 3, 1, and 2 is
presented here. Results of neurophysiological studies, i.e., recordings of single
neuronal activities in these three cytoarchitectonic areas of the monkey brain
are described and interpreted on the basis of a hierarchial schema model of
information processing. Finally, recent studies on the human postcentral gyrus
are reviewed and compared with the results of the aforementioned monkey studies.
PMID- 28424387
TI - [Cortical Areas for Controlling Voluntary Movements].
AB - The primary motor cortex is located in Brodmann area 4 at the most posterior part
of the frontal lobe. The primary motor cortex corresponds to an output stage of
motor signals, sending motor commands to the brain stem and spinal cord. Brodmann
area 6 is rostral to Brodmann area 4, where multiple higher-order motor areas are
located. The premotor area, which is located in the lateral part, is involved in
planning and executing action based on sensory signals. The premotor area
contributes to the reaching for and grasping of an object to achieve a behavioral
goal. The supplementary motor area, which occupies the mesial aspect, is involved
in planning and executing actions based on internalized or memorized signals. The
supplementary motor area plays a central role in bimanual movements, organizing
multiple movements, and switching from a routine to a controlled behavior. Thus,
Brodmann areas 4 and 6 are considered as central motor areas in the cerebral
cortex, in which the idea of an action is transformed to an actual movement in a
variety of contexts.
PMID- 28424388
TI - [Interface Between Brain and Outside].
AB - Areas 5 and 7 are the association cortices which are located in the parietal lobe
and process somatosensory and visual information, respectively. The location of
area 7 differ in the Brodmann's human and monkey brain map, in the human brain
map area 7 is located in the superior parietal lobe, while it is in the inferior
parietal lobe in the monkey brain map. Thus, it is difficult to discuss the
function of these areas.
PMID- 28424389
TI - [Brodmann Areas 8 and 9 Including the Frontal Eye Field].
AB - Based on cytoarchitectonic analyses, Brodmann assigned numbers 8 and 9 to certain
areas of the dorsal and medial prefrontal cortex (PFC) in humans and monkeys.
Petrides and Pandya re-analyzed the cytoarchitectures of the human and monkey
PFCs, and proposed slightly different brain maps for both species. They assigned
numbers 8, 9 and 9/46 to the areas that were originally named areas 8 and 9.
Areas 8 and 9 have both lateral and medial regions respectively. The lateral area
8 is important for conditional discrimination learning. The frontal eye field
which occupies the most caudal region of area 8, is responsible for visual
attention and control of eye movements. The lateral area 9 and area 9/46 are
functionally similar to area 46 and play important roles in executive control.
The dorsomedial prefrontal cortex (DMPFC) comprises the medial regions of areas 8
and 9 and is related to "Theory of Mind" and social cognition. The DMPFC is also
known to show "default mode of brain activity" (i.e., more activity during rest
than during cognitive task).
PMID- 28424390
TI - [Area 10, 38: Prospective Functions in BA10 and Semantic Hub in BA38].
AB - This paper reviews the structural specificities and functional roles in Brodmann
areas 10 and 38. A number of studies have focused on both areas through various
approaches including neuropsychology, neuroimaging, psychiatry, neurology, and
neurosurgery. Both areas 10 and 38 may have a substantially very complex higher
order cognitive functions, which are quite hard to disentangle. Here, I picked up
some fundamental perspectives for reviewing previous studies, to provide
efficient research orientations for the elucidation of functions in both areas.
PMID- 28424391
TI - [Brodmann Areas 11, 46, and 47: Emotion, Memory, and Empathy].
AB - Brodmann area 11 is one of the main constituent of the orbitofrontal cortex, and
area 46 is that of the dorsolateral prefrontal cortex. The main function of
Brodmann area 11 is the processing of emotion and value, whereas the main
function of Brodmann area 46 is the processing of cognitive information,
including working memory. In comparison, the function of area 47 is more complex.
This area is related to the feeling of empathy towards the story contents of
others, which is thought to be the emotional aspect of this area, while this area
is also activated during automated action. This is in contrast with the function
of area 46, which is involved in willed action. In addition, area 47 in the left
hemisphere plays an important role in syntax processing.
PMID- 28424392
TI - [The Role of Brodmann Area 12: Taste, Social Cognition, and Mental Time].
AB - Broadman area 12, together with area 11, is located in the orbitofrontal area. A
voxel-based morphometric (VBM) study revealed the association between bilateral
brodmann areas 12/47 and taste disturbance in individuals with frontotemporal
lobar degeneration (FTLD). In our VBM study in patients with Parkinson's disease,
decision-making impairments were associated with atrophy of the bilateral
Brodmann area 12, indicating that this area may play an important role in social
cognitive function. Our recent study also demonstrated that this area may serve
as time order judgement or mental time travel.
PMID- 28424393
TI - [Regulation of Behavior Based on Interoception].
AB - It is well known that the insular cortex (Brodmann areas 13, 14, 15, and 16)
located deep inside the Sylvian fissure is associated with mental functions such
as perception, language, cognition, affect, and movement. In particular, the
insular cortex has been linked to interoception, which is the representation of
bodily physiological states that is used to regulate bodily states and mental
functions. Recently, a common principle to explain such functions of the insular
cortex has been proposed. The principle posits that the anterior insula generates
predictions of future bodily states, computes the error by comparing the
prediction with the actual sensory signals, and integrates the body with the mind
by minimizing the prediction error. This article describes the functions of the
insular cortex, and discusses the possibility that an error-minimizing function
can affect decision-making to regulate behaviors.
PMID- 28424394
TI - [Brodmann Areas 17, 18, and 19 in the Human Brain: An Overview].
AB - Brodmann areas 17, 18, and 19 in the human brain are visual cortices of the
occipital lobe. Each area has its own retinotopic representations, particulary
area 19, which has many small retinotopic areas representing half or all of the
contralateral visual field, several functional areas, and nine cytoarchitectonic
areas. Several fasciculi are known as occipital fiber connections, but their
precise endpoints are not clear. Lesions in the visual cortices cause several
visual disorders including visual field defect, visual hallucinations,
metamorphopsia, and different kinds of visual agnosia.
PMID- 28424395
TI - [Brodmann Areas 20, 21, and 22 in the Cerebral Cortex].
AB - The 20, 21, and 22 areas in the temporal lobe as classified by Brodmann are
almost identical with Economo and Koskinas's TA, TE1, and TE2, and, generally,
with the gyrus, middle temporal gyrus, and inferior temporal gyrus according to
brain anatomy. Before Brodmann's classification, Flechsig published his book
"Soul and Brain" in 1897, in which primary, secondary, and association areas in
the brain were classified. More recently, results from research using magnetic
resonance imaging (MRI) and fMRI support the parcellation of the cerebral cortex
proposed by Flechsig, Brodmann, and Economo more than one century ago.
PMID- 28424396
TI - [The Center of Sadness, Pain, and Recognition].
AB - The posterior cingulate cortex (Brodmann area, BA 23) is the hub of the default
mode network (DMN). Moreover, its network connectivity decreases early in
Alzheimer disease. The anterior cingulate cortex (BA 24) is connected to networks
such as the DMN, working memory network (WMN), and salience network (SN) and
plays a role in network coordination. The subgenual anterior cingulate cortex
(sgACC) on the rostral region of the anterior cingulated cortex is suggested to
be associated with depression.
PMID- 28424397
TI - [Spatial Cognition and Episodic Memory Formation in the Limbic Cortex].
AB - The limbic lobe defined by Broca is a cortical region with highly diverse
structure and functions, and comprises the paleo-, archi-, and neocortices as
well as their transitional zones. In the limbic lobe, Brodmann designated areas
27, 28, 34, 35, and 36 adjacent to the hippocampus, and areas 23, 24, 25, 26, 29,
30, 31, 32, and 33 around the corpus callosum. In the current literature, areas
27 and 28 correspond to the presubiculum and entorhinal cortex, respectively.
Area 34 represents the cortico-medial part of the amygdaloid complex. Areas 35
and 36 roughly cover the perirhinal and parahippocampal cortices. Areas 24, 25,
32, and 33 belong to the anterior cingulate gyrus, while areas 23, 26, 29, 30,
and 31 to the posterior cingulate gyrus. Areas 25, 32, and the anteroinferior
portion of area 24 are deeply involved in emotional responses, particularly in
their autonomic functions, through reciprocal connections with the amygdaloid
complex, anterior thalamus and projections to the brainstem and spinal visceral
centers. Areas 29 and 30 have dense reciprocal connections with areas 23 and 31,
the dorsolateral prefrontal areas, and the regions related to the hippocampus.
They play pivotal roles in mediating spatial cognition, working memory
processing, and episodic memory formation.
PMID- 28424398
TI - [Brodmann Areas 27, 28, 36 and 37: The Parahippocampal and the Fusiform Gyri].
AB - First, Brodmann areas 27, 28, 36 and 37, were anatomically defined in the
beginning of this review. These areas exist in the parahippocampal or fusiform
gyrus of the ventral temporal lobe in humans. Subsequently, the current
understanding of their functions was summarized on the basis of recent findings
mainly through human functional neuroimaging studies and animal studies. Rodent
studies have shown the existence of neuronal activities for representing space,
such as those involving head-direction cells or grid cells, in areas 27 (the
parasubicular cortex) and 28 (the ventral entorhinal cortex). Recent human
neuroimaging studies have provided support for the idea that grid cells may also
exist in the human entorhinal cortex. Many previous animal studies have shown
that area 36 (the lateral perirhinal cortex) is crucial for various types of
associative learning. Earlier human neuroimaging studies have also indicated that
faces, bodies and visual word forms are represented in different regions of area
37 in the posterior fusiform gyrus. Recent neuroimaging studies in humans have
shown substantial functional differentiation between face-related regions in
areas 37 and 36, which is similar to that seen in macaque monkeys, as shown
through their face patches. This implies the crucial involvement of both areas in
face processing.
PMID- 28424399
TI - [Recent Advancements in Understanding Hippocampal Functions].
AB - The hippocampal formation located in the medial temporal lobe of the brain has
been studied extensively for several decades, both in in vitro slice preparations
and in vivo living animals. Recent advancements in large-scale recording
techniques, such as multisite silicon probes and tetrodes, enable us to examine
the detailed characteristics of temporal spiking patterns of tens or hundreds of
neurons in the hippocampal circuit. Here, we introduce how such tools contribute
to our understanding of the hippocampal network dynamics and review several
hippocampal functions for information processing in the brain, including pattern
separation and completion, spatial representation, and encoding of positive and
negative valence.
PMID- 28424400
TI - [Brodmann Areas 39 and 40: Human Parietal Association Area and Higher Cortical
Function].
AB - The anatomy and function of the angular gyrus (Brodmann Area 39) and
supramarginal gyrus (Brodmann Area 40) are described here. Both gyri constitute
the inferior part of the parietal lobe. Association fibers from the angular gyrus
project to the dorsolateral prefrontal cortex via the superior longitudinal
fasciculus (SLF) II/arcuate fasciculus (AF), whereas those from the supramarginal
gyrus project to the ventrolateral prefrontal cortex via SLF III/AF. Damage to
the left angular gyrus causes kanji agraphia (lexical agraphia) and mild anomia,
whereas damage to the left supramarginal gyrus causes kana alexia (phonological
dyslexia) and kana agraphia (phonological agraphia). Damage to either gyrus
causes Gerstmann's syndrome (finger agnosia, left-right disorientation, agraphia
and acalculia) and verbal short-term memory impairment. "Angular alexia with
agraphia" results from damage to the middle occipital gyrus posterior to the
angular gyrus. Alexia and agraphia, with lesions in the angular or supramarginal
gyrus, are characterized by kana transposition errors in reading words, which
suggests the impairment of sequential phonological processing.
PMID- 28424401
TI - [The Map of Auditory Function].
AB - Brodmann areas 41 and 42 are located in the superior temporal gyrus and regarded
as auditory cortices. The fundamental function in audition is frequency analysis;
however, the findings on tonotopy maps of the human auditory cortex were not
unified until recently when they were compared to the findings on inputs and
outputs of the monkey auditory cortex. The auditory cortex shows plasticity after
conditioned learning and surgery of cochlear implant. It is also involved in
speech perception, music appreciation, and auditory hallucination in
schizophrenia through interactions with other brain areas, such as the thalamus,
frontal cortex, and limbic systems.
PMID- 28424402
TI - [Syntactic Processing in Broca's Area: Brodmann Areas 44 and 45].
AB - Brodmann areas 44 and 45 are known as Broca's area; however, their true
functional roles are still unknown. Recent developments in neuroimaging
techniques revealed the structures and functions of Broca's area in detail. More
specifically regarding language functions, sufficient evidence has been
accumulated that this region subserves the center of syntactic processing, not
necessarily motor functions. Here, we review a role of Broca's area as the
grammar center, including other roles in nonlinguistic functions.
PMID- 28424403
TI - [Non-Convulsive Status Epilepticus Caused by Hyponatremia in an Elderly Woman: A
Case Report].
AB - We report the case of a 67-year-old woman with non-convulsive status epilepticus
(NCSE) due to hyponatremia. She had a history of psychogenic polydipsia but not
epilepsy. She was admitted to our hospital with dysbulia. On admission, she was
confused and disoriented (Glasgow Coma Scale: 6, E1V1M4). Magnetic resonance
imaging of the brain showed no abnormalities. Laboratory test showed hyponatremia
(Na+ level: 115 mEq/L). The electroencephalography (EEG) showed a
generalized slow wave of 5 Hz during recording. The slow wave was promptly
suppressed by diazepam and levetiracetam administered intravenously and orally,
respectively. After the hyponatremia was treated the seizures stopped and did not
reoccur, even after cessation of the anticonvulsant drugs. The patient was
discharged with no neurological deficits. Few reports have described this
condition. Here we discuss the diagnosis and treatment of NCSE due to
hyponatremia. (Received May 31, 2016; Accepted December 12, 2016; Published April
1, 2017).
PMID- 28424404
TI - Upregulation of minichromosome maintenance complex component 3 during epithelial
to-mesenchymal transition in human prostate cancer.
AB - Metastasis is often associated with epithelial-to-mesenchymal transition (EMT).
To understand the molecular mechanisms of this process, we conducted proteomic
analysis of androgen-repressed cancer of the prostate (ARCaP), an experimental
model of metastatic human prostate cancer. The protein signatures of epithelial
(ARCaPE) and mesenchymal (ARCaPM) cells were consistent with their phenotypes.
Importantly, the expression of mini-chromosome maintenance 3 (MCM3) protein, a
crucial subunit of DNA helicase, was significantly higher in ARCaPM cells than
that of ARCaPE cells. This increased MCM3 protein expression level was verified
using Western blot analysis of the ARCaP cell lineages. Furthermore,
immunohistochemical analysis of MCM3 protein levels in human prostate tissue
specimens showed elevated expression in bone metastasis and advanced human
prostate cancer tissue samples. Subcutaneous injection experiments using ARCaPE
and ARCaPM cells in a mouse model also revealed increased MCM3 protein levels in
mesenchymal-derived tumors. This study identifies MCM3 as an upregulated molecule
in mesenchymal phenotype of human prostate cancer cells and advanced human
prostate cancer specimens, suggesting MCM3 may be a new potential drug target for
prostate cancer treatment.
PMID- 28424405
TI - The Bruton's tyrosine kinase inhibitor ibrutinib exerts immunomodulatory effects
through regulation of tumor-infiltrating macrophages.
AB - The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising
efficacy in a variety of hematologic malignancies. However, the precise mechanism
of action of the drug remains to be fully elucidated. Tumor-infiltrating
macrophages presented in the tumor microenvironment have been shown to promote
development and progression of B-cell lymphomas through crosstalk mediated by
secreted cytokines and chemokines. Because Btk has been implicated in Toll-like
receptor (TLR) signaling pathways that regulate macrophage activation and
production of proinflammatory cytokines, we investigated the immunomodulatory
effects of Btk inhibitor on macrophages. Our results demonstrate that Btk
inhibition efficiently suppresses production of CXCL12, CXCL13, CCL19, and VEGF
by macrophages. Furthermore, attenuated secretion of homeostatic chemokines from
Btk inhibitor-treated macrophages significantly compromise adhesion, invasion,
and migration of lymphoid malignant cells and even those not driven by Btk
expression. The supernatants from Btk inhibitor-treated macrophages also impair
the ability of endothelial cells to undergo angiogenic tube formation.
Mechanistic analysis revealed that Btk inhibitors treatment downregulates
secretion of homeostatic chemokines and cytokines through inactivation of Btk
signaling and the downstream transcription factors, NF-kappaB, STAT3, and AP-1.
Taken together, these results suggest that the encouraging therapeutic efficacy
of Btk inhibitor may be due to both direct cytotoxic effects on malignant B cells
and immunomodulatory effects on macrophages present in the tumor
microenvironment. This novel mechanism of action suggests that, in addition to B
cell lymphomas, Btk inhibitor may also have therapeutic value in lymphatic
malignancies and solid tumors lacking Btk expression.
PMID- 28424406
TI - Targeting CCR2 with its antagonist suppresses viability, motility and invasion by
downregulating MMP-9 expression in non-small cell lung cancer cells.
AB - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which
is the leading cancer killer in the world. Despite the recent advances in its
diagnosis and therapy, the prognosis of NSCLC patients remains very poor, mainly
due to the development of drug resistance and metastasis. Both the chemokine
network and the matrix metalloproteinase (MMP) system play important roles in
cancer cell metastasis. The disruption of CCL2/CCR2 chemokine signaling has been
shown to suppress cancer cellviability and metastasis. CCL2-neutralizing
antibodies, which have shown promising therapeutic efficacy in several cancer
models, are not widely used due to technical issues. CCR2 antagonism has thus
become an alternative method for cancer treatment. However, the effect of CCR2
antagonists on NSCLC progression remains poorly understood. Here, we investigated
the effect of CCR2 antagonist (CAS445479-97-0) on the proliferation, migration
and invasion of human lung adenocarcinoma A549 cells by using WST-1 cell
viability assay, transwell migration assay, wound healing scratch assay and
Matrigel invasion assay. We demonstrated that CCL2 treatment promoted A549 cell
viability, motility and invasion by upregulating MMP-9 expression and that this
induction was significantly suppressed by CAS 445479-97-0. Taken together, our
data suggested that the CCR2 antagonist would be a potential drug for treating
CCR2-positive NSCLC patients.
PMID- 28424407
TI - The expression of histone deacetylase HDAC1 correlates with the progression and
prognosis of gastrointestinal malignancy.
AB - Gastrointestinal malignancy is a severe public health threat worldwide, and
survival for most types of gastrointestinal cancer is very poor. Therefore,
finding better cancer biomarkers to diagnose gastrointestinal malignancy and
predict patient survival is essential. HDAC1 has been reported to be closely
associated with several types of cancer, but the precise role of HDAC1 in
gastrointestinal cancer is not clear. Recently, quite a few studies have
investigated the correlation between HDAC1 expression and clinical features or
prognosis in multiple types of gastrointestinal malignancies, but the results
were inconsistent. In this study, we systematically reviewed the association
between HDAC1 and gastrointestinal malignancy using meta-analysis methods, and 28
eligible studies were analyzed. We found that the expression level of HDAC1 in
gastrointestinal malignancies, especially in colorectal cancer (OR = 10.84, 95%
CI = 5.33-22.07, P< 0.00001), was higher than that in noncancerous tissue, and
HDAC1 expression was closely associated with some clinical features of
gastrointestinal cancer patients, such as tumor stage (OR = 1.62, 95% CI = 1.28
2.05, P < 0.0001) and tumor grade (OR = 1.75, 95% CI = 1.03-2.95, P = 0.04). In
addition, we also found that patients with low HDAC1 expression showed better
overall survival than those with high HDAC1 expression in gastrointestinal
malignancy, especially in gastric cancer (HR = 1.88, 95% CI = 1.14-3.12, P =
0.01). Our results strongly suggest that HDAC1 may serve as a good diagnostic and
prognostic marker for gastrointestinal malignancy.
PMID- 28424408
TI - Synthetic lethality of glutaminolysis inhibition, autophagy inactivation and
asparagine depletion in colon cancer.
AB - Cancer cells reprogram metabolism to coordinate their rapid growth. They addict
on glutamine metabolism for adenosine triphosphate generation and macromolecule
biosynthesis. In this study, we report that glutamine deprivation retarded cell
growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine
significantly enhanced glutamine starvation induced growth inhibition and
apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth
inhibition induced by glutamine starvation and autophagy blockage. Similar to
glutamine starvation, inhibition of glutamine metabolism with a chemical
inhibitor currently under clinical evaluation was synthetically lethal with
chloroquine and L-asparaginase, drugs approved for the treatment of malaria and
leukemia, respectively. In conclusion, inhibiting glutaminolysis was
synthetically lethal with autophagy inhibition and asparagine depletion.
Therefore, targeting glutaminolysis could be a promising approach for colorectal
cancer treatment.
PMID- 28424409
TI - Clinical genomic profiling to identify actionable alterations for investigational
therapies in patients with diverse sarcomas.
AB - BACKGROUND: There are currently no United States Food and Drug Administration
approved molecularly matched therapies for sarcomas except gastrointestinal
stromal tumors. Complicating this is the extreme diversity, heterogeneity, and
rarity of these neoplasms. Few therapeutic options exist for relapsed and
refractory sarcomas. In clinical practice many oncologists refer patients for
genomic profiling hoping for guidance on treatment options after standard
therapy. However, a systematic analysis of actionable mutations has yet to be
completed. We analyzed genomic profiling results in patients referred to MD
Anderson Cancer Center with advanced sarcomas to elucidate the frequency of
potentially actionable genomic alterations in this population. METHODS: We
reviewed charts of patients with advanced sarcoma who were referred to
investigational cancer therapeutics department and had CLIA certified
comprehensive genomic profiling (CGP) of 236 or 315 cancer genes in at least 50ng
of DNA. Actionable alterations were defined as those identifying anti-cancer
drugs on the market, in registered clinical trials, or in the Drug-Gene
Interaction Database. RESULTS: Among the 102 patients analyzed median age was
45.5 years (range 8-76), M: F ratio 48:54. The most common subtypes seen in our
study were leiomyosarcoma (18.6%), dedifferentiated liposarcoma (11%),
osteosarcoma (11%), well-differentiated liposarcoma (7%), carcinosarcoma (6%),
and rhabdomyosarcoma (6%). Ninety-five out of 102 patients (93%) had at least one
genomic alteration identified with a mean of six mutations per patient. Of the 95
biopsy samples with identifiable genomic alterations, the most commonly affected
genes were TP53 (31.4%), CDK4 (23.5%), MDM2 (21.6%), RB1 (18.6%), and CDKN2A/B
(13.7%). Notable co-segregating amplifications included MDM2-CDK4 and FRS2-FGF.
Sixteen percent of patients received targeted therapy based on CGP of which 50%
had at least stable disease. CONCLUSIONS: Incorporating CGP into sarcoma
management may allow for more precise diagnosis and sub-classification of this
diverse and rare disease, as well as personalized matching of patients to
targeted therapies such as those available in basket clinical trials.
PMID- 28424411
TI - Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-,
and Hsp90-inhibition of glioblastoma cells with different invasive capacities.
AB - High invasiveness and resistance to chemo- and radiotherapy of glioblastoma
multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment
strategies for preventing migration and invasion of GBM cells are needed. Using
two different migration assays, Western blotting, conventional and super
resolution (dSTORM) fluorescence microscopy we examine the effects of the dual
PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP
AUY922 and/or irradiation on the migration, expression of marker proteins, focal
adhesions and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19)
markedly differing in their invasive capacity. Both lines were found to be
strikingly different in morphology and migration behavior. The less invasive DK
MG cells maintained a polarized morphology and migrated in a directionally
persistent manner, whereas the highly invasive SNB19 cells showed a multipolar
morphology and migrated randomly. Interestingly, a single dose of 2 Gy
accelerated wound closure in both cell lines without affecting their migration
measured by single-cell tracking. PI-103 inhibited migration of DK-MG (p53 wt,
PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells probably due to aberrant
reactivation of the PI3K pathway in SNB19 cells treated with PI-103. In contrast,
NVP-AUY922 exerted strong anti-migratory effects in both cell lines. Inhibition
of cell migration was associated with massive morphological changes and
reorganization of the actin cytoskeleton. Our results showed a cell line-specific
response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude that
anti-migratory agents warrant further preclinical investigation as potential
therapeutics for treatment of GBM.
PMID- 28424412
TI - FBXW7 missense mutation: a novel negative prognostic factor in metastatic
colorectal adenocarcinoma.
AB - BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant
oncogenic proteins and commonly mutates in colorectal cancer. Data suggest
missense mutations lead to greater loss of FBXW7 function than other gene
aberrations do. However, the clinicopathologic factors and outcomes associated
with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not
been described. METHODS: Data were obtained from mCRC patients whose tumors were
evaluated by next-generation sequencing for hotspot mutations at The University
of Texas MD Anderson Cancer Center. Alterations in FBXW7 were identified, and
their associations with clinicopathologic features and overall survival (OS) were
evaluated. RESULTS: Of 855 mCRC patients, 571 had data on FBXW7 status; 43 (7.5%)
had FBXW7 mutations, including 37 with missense mutations. R465C mutations in
exon 9 were the most common missense mutations (18.6%). PIK3CA mutations were
associated with FBXW7 missense mutations (p=0.012). On univariate analysis,
patients with FBXW7 missense mutations had significantly worse OS (median 28.7
mo) than those with wild-type FBXW7 (median 46.6 mo; p=0.003). On multivariate
analysis including other known prognostic factors such as BRAF mutations, FBXW7
missense mutations were the strongest negative prognostic factor for OS (hazard
ratio 2.0; p=0.003). CONCLUSIONS: In the largest clinical dataset of mCRC to
date, FBXW7 missense mutations showed a strong negative prognostic association.
PMID- 28424413
TI - The SNAIL/miR-128 axis regulated growth, invasion, metastasis, and epithelial-to
mesenchymal transition of gastric cancer.
AB - miR-128 is expressed in various tumors, but its expression and function in
gastric cancer have not been defined. Thus, the goal of this study was to
characterize miR-128 in gastric cancer. We found first that miR-128 is down
regulated in gastric cancer cell lines and tissues, and this dysregulation is
correlated with DNA methylation and the transcription factor SNAIL. Using
prediction tools, western blotting, and luciferase reporter assays, we found that
Bmi-1 was the direct target of miR-128. Additionally, overexpression of miR-128
inhibited gastric cancer cell migration, invasion, and proliferation by targeting
Bmi-1 in vitro and in vivo. We also documented, with receiver operating
characteristic curves and Kaplan-Meier survival analysis, that miR-128 and Bmi-1
may be useful markers for diagnosing and estimating the prognosis of gastric
cancer patients. As the epithelial-to-mesenchymal transition is an important
mechanism associated with cancer invasion and metastasis, we inferred that miR
128 could regulate this mechanism in gastric cancer. In fact, we found that miR
128 could reverse epithelial-to-mesenchymal transition induced by Bmi-1 via the
PI3K/AKT pathway. Because SNAIL also acts as a mesenchymal marker, our findings
identified a novel positive feedback loop in which the transcription factor SNAIL
curbs the expression of miR-128, and then down-regulated miR-128 promotes the
expression of Bmi-1; finally, overexpression of Bmi-1 drives the epithelial-to
mesenchymal transition process via the PI3K/AKT pathway, and the expression of
SNAIL is up-regulated.
PMID- 28424414
TI - Integrated analysis of promoter methylation and expression of telomere related
genes in breast cancer.
AB - Telomeres at the ends of eukaryotic chromosomes play a critical role in
tumorgenesis. Using microfluidic PCR and next-generation bisulfite sequencing
technology, we investigated the promoter methylation of 29 telomere related genes
in paired tumor and normal tissues from 184 breast cancer patients. The
expression of significantly differentially methylated genes was quantified using
qPCR method.We observed that the average methylation level of the 29 telomere
related genes was significant higher in tumor than that in normal tissues (P =
4.30E-21). A total of 4 genes (RAD50, RTEL, TERC and TRF1) showed significant
hyper-methylation in breast tumor tissues. RAD51D showed significant methylation
difference among the four breast cancer subtypes. The methylation of TERC showed
significant association with ER status of breast cancer. The expression profiles
of the 4 hyper-methylated genes showed significantly reduced expression in tumor
tissues. The integration analysis of methylation and expression of these 4 genes
showed a good performance in breast cancer prediction (AUC = 0.947).Our results
revealed the methylation pattern of telomere related genes in breast cancer and
suggested a novel 4-gene panel might be a valuable biomarker for breast cancer
diagnosis.
PMID- 28424415
TI - Clinicopathological features and outcome of chronic lymphocytic leukaemia in
Chinese patients.
AB - Chronic lymphocytic leukaemia (CLL) is uncommon in Chinese population and its
biology, genetics and treatment outcome in Chinese patients have not been
comprehensively investigated. In this study, we studied the clinicopathological
features and outcome of 212 Chinese patients with newly diagnosed CLL in Hong
Kong and Singapore. The median age at diagnosis was 64 years. The majority of
patients presented with early-stage disease (Binet stage A, 56.1%). Del(13)(q14)
was the most frequent abnormality (41.7%) detected by fluorescence in situ
hybridization (FISH) analysis. Del(17p) and TP53 gene mutations were detected in
7.8% and 8.2% of patients, respectively. MYD88 mutations were found at a higher
frequency (11.5%) than expected. CLL with unmutated variable region of the
immunoglobulin heavy chain genes (IGHV) occurred in only 31.2% of cases, and was
associated with advanced-stage disease (p <0.01) and adverse FISH abnormalities
(p<0.01). With a median follow-up of 39 months, the median overall survival (OS)
was 108 months. The presence of del(17p) or TP53 mutations was associated with a
significantly shorter time to first treatment and an inferior OS (p <0.01).
Unmutated IGHV was also associated with a significantly shorter time to treatment
(p <0.01). Among patients who required treatment, the median OS and progression
free survival (PFS) were 107 and 23 months, respectively. The presence of
del(17p) was associated with a significantly inferior OS and PFS (p <0.01). In
summary, Chinese CLL patients had similar genetic aberrations at diagnosis
compared with those of Western populations. FISH abnormalities are major factors
affecting outcome.
PMID- 28424416
TI - Loss of thyroid hormone receptor interactor 13 inhibits cell proliferation and
survival in human chronic lymphocytic leukemia.
AB - BACKGROUND: The genetic regulation of apoptosis and cell proliferation plays a
role in the growth of chronic lymphocytic leukemia (CLL), the most common form of
leukemia in the Western hemisphere. Although thyroid hormone receptor interactors
(TRIPs) are known to play roles in cell cycle, the potential involvement of the
novel family member TRIP13 in CLL has not yet been investigated. METHODS:
Quantitative PCR (qPCR) was used to detect expression of TRIP13 in 36 CLL
patients and 33 healthy donors CD19+ B cells. Loss-of-function (siRNA) assays
were used to alter TRIP13 expression levels. The effect of TRIP13 on cell
proliferation and apoptosis was measured by MTT, Annexin V-based flow cytometry
and Caspase 3/7 activity assay. Affymetrix GeneChip and Ingenuity Pathway
Analysis (IPA) were used to describe an overview of TRIP13 potential biological
function and downstream pathways. Dual-luciferase reporter assay was performed to
assess the promoting effect of c-MYC on TRIP13 transcription. RESULTS: The qPCR
data showed that TRIP13 is significantly over-expressed in CLL patients.
Microarray analyses indicated that the biological function of TRIP13 in CLL is
majorly cell apoptosis and cell proliferation associated. TRIP13 siRNA expressing
cells exhibited a slower cell proliferation rate and underwent apoptosis compared
with control cells. TRIP13 knockdown induced CLL cells apoptosis through PUMA
independent of p53. TRIP13 up-regulation is induced by c-MYC dependent
transcriptional activation. CONCLUSION: Overall, our data suggest the bio
function of TRIP13 in CLL cell for the first time, and that this gene might be a
therapeutic target for CLL.
PMID- 28424417
TI - Mesenchymal stem cells differentially affect the invasion of distinct
glioblastoma cell lines.
AB - Glioblastoma multiforme are an aggressive form of brain tumors that are
characterized by distinct invasion of single glioblastoma cells, which infiltrate
the brain parenchyma. This appears to be stimulated by the communication between
cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the
glioblastoma microenvironment, and their 'cross-talk' with glioblastoma cells is
still poorly understood. Here, we examined the effects of bone marrow-derived
MSCs on two different established glioblastoma cell lines U87 and U373. We
focused on mutual effects of direct MSC/glioblastoma contact on cellular invasion
in three-dimensional invasion assays in vitro and in a zebrafish embryo model in
vivo. This is the first demonstration of glioblastoma cell-type-specific
responses to MSCs in direct glioblastoma co-cultures, where MSCs inhibited the
invasion of U87 cells and enhanced the invasion of U373. Inversely, direct cross
talk between MSCs and both of glioblastoma cell lines enhanced MSC motility. MSC
enhanced invasion of U373 cells was assisted by overexpression of proteases
cathepsin B, calpain1, uPA/uPAR, MMP-2, -9 and -14, and increased activities of
some of these proteases, as determined by the effects of their selective
inhibitors on invasion. In contrast, these proteases had no effect on U87 cell
invasion under MSC co-culturing. Finally, we identified differentially expressed
genes, in U87 and U373 cells that could explain different response of these cell
lines to MSCs. In conclusion, we demonstrated that MSC/glioblastoma cross-talk is
different in the two glioblastoma cell phenotypes, which contributes to tumor
heterogeneity.
PMID- 28424418
TI - The aryl hydrocarbon receptor is required for induction of p21cip1/waf1
expression and growth inhibition by SU5416 in hepatoma cells.
AB - The aryl hydrocarbon receptor (AhR) is a potential clinical target for cancer and
autoimmune dysfunction. Identifying selective AhR modulators that produce
desirable clinical outcomes represents an opportunity for developing new anti
cancer agents. Repurposing clinically-used drugs with established safety profiles
that activate the AhR represents a good starting place to pursue this goal. In
this study, we characterized the AhR-dependent effects of SU5416 (Semaxanib)
following its identification in a small-molecule library screen. SU5416 potently
activated AhR-dependent reporter genes, induced AhR nuclear localization,
facilitated AhR-DNA binding, and increased, expression of its endogenous target
genes. SU5416 significantly inhibited proliferation of Hepa1 hepatoma cells in an
AhR-dependent manner, but did not induce apoptosis. SU5416 also inhibited the
growth of human HepG2 liver cancer cells. The effects of SU5416 correlated with
an increased G1 population and increased expression of cell cycle inhibitor
p21cip1/waf1 at both the mRNA and protein level. Increased expression of
p21cip1/waf1 by SU5416 required expression of both AhR and Arnt. In addition,
evidence for long-term activation of the AhR in vivo by a single dose of SU5416
was identified by analyzing published microarray data. Our results provide
support for continued investigation of the AhR as therapeutic for cancers such as
hepatocellular carcinoma. In addition, our findings raise the possibility that
some of the previously observed anti-proliferative effects of SU5416 may be due
to activation of the AhR.
PMID- 28424419
TI - Integrated analysis of genes associated with poor prognosis of patients with
colorectal cancer liver metastasis.
AB - Colorectal cancer (CRC) is one of the most common malignances in the gut. Liver
is the most common metastasis site of CRC. This study focuses on the primary CRC
and its liver metastasis, aiming to discover several liver metastasis related
genes and provide therapeutic candidates. We compared gene expression patterns
among the groups of normal colorectal mucosa, primary tumor and the liver
metastasis using a CRC gene expression dataset. 84 genes were found to be
upregulated in both primary tumor and liver metastases. Function enrichment
analysis indicated that these genes are enriched in pathways such as chemotaxis,
coagulation and lipid metabolism which are crucial in multi-step cancer
metastasis. Gene network analysis identified several important hub genes that may
be involved in carcinogenesis and liver metastasis. Then we used a validation
dataset containing 562 CRC samples with detailed clinical information, to screen
prognostic biomarkers for overall survival (OS) and relapse free survival (RFS).
Finally, overexpression of THBS2 (thrombospondin 2), INHBB (inhibin, beta B) and
BGN (biglycan) were proved to be correlated with poor OS and RFS. In conclusion,
this study indicated that chemotaxis, coagulation and lipid metabolism might play
critical roles in the processes of carcinogenesis and liver metastasis. THBS2,
INHBB and BGN are prognostic markers and potential therapeutic targets for CRC.
PMID- 28424420
TI - Vitexin protects against hypoxic-ischemic injury via inhibiting Ca2+/Calmodulin
dependent protein kinase II and apoptosis signaling in the neonatal mouse brain.
AB - Neonatal hypoxic-ischemic is a major cause of death and disability in neonates.
In this study, we suggest for the first time that pretreatment with vitexin may
suppress a pro-apoptotic signaling pathway in hypoxic-ischemic neuronal injury in
neonates by inhibition of the phosphorylation of Ca2+/Calmodulin-dependent
protein kinase II. Here we found that vitexin pretreatment reduced brain infarct
volume in a dose-dependent manner. In addition, vitexin decreased the number of
TUNEL-positive cells and brain atrophy. Furthermore, vitexin improved
neurobehavioral outcomes. Vitexin also reduced oxygen glucose deprivation-induced
neuronal injury and calcium entry. Vitexin pretreatment increased the Bcl-2/Bax
protein ratio and decreased phosphorylation of Ca2+/Calmodulin-dependent protein
kinase II and NF-kappaB, cleaved caspase-3 protein expression 24 hours after
injury. Our data indicate that pretreatment with vitexin protects against
neonatal hypoxic-ischemic brain injury and thus has potential as a treatment for
hypoxic-ischemic brain injury.
PMID- 28424421
TI - The soy-derived peptide Lunasin inhibits invasive potential of melanoma
initiating cells.
AB - Lunasin is a 44 amino acid peptide with multiple functional domains including an
aspartic acid tail, an RGD domain, and a chromatin-binding helical domain. We
recently showed that Lunasin induced a phenotype switch of cancer initiating
cells (CIC) out of the stem compartment by inducing melanocyte-associated
differentiation markers while simultaneously reducing stem-cell-associated
transcription factors. In the present study, we advance the hypothesis that
Lunasin can reduce pools of melanoma cells with stem cell-like properties, and
demonstrate that Lunasin treatment effectively inhibits the invasive potential of
CICs in vitro as well as in vivo in a mouse experimental metastasis model. Mice
receiving Lunasin treatment had significantly reduced pulmonary colonization
after injection of highly metastatic B16-F10 melanoma cells compared to mice in
the control group. Mechanistic studies demonstrate that Lunasin reduced
activating phosphorylations of the intracellular kinases FAK and AKT as well as
reduced histone acetylation of lysine residues in H3 and H4 histones. Using
peptides with mutated activity domains, we functionally demonstrated that the RGD
domain is necessary for Lunasin uptake and its ability to inhibit oncosphere
formation by CICs, thus confirming that Lunasin's ability to affect CICs is at
least in part due to the suppression of integrin signaling. Our studies suggest
that Lunasin represents a unique anticancer agent that could be developed to help
prevent metastasis and patient relapse by reducing the activity of CICs which are
known to be resistant to current chemotherapies.
PMID- 28424422
TI - Limited impact of intratumour heterogeneity on molecular risk assignment in
endometrial cancer.
AB - INTRODUCTION: Individual prediction of tumour behaviour based on molecular
markers may refine adjuvant treatment strategies in endometrial cancer (EC). As
these molecular alterations are determined in a small tumour fraction, high
intratumour heterogeneity may interfere with correct risk prediction. This study
aimed to investigate to which extent intratumour heterogeneity exists for
molecular markers and whether it affects the molecular risk assignment in EC.
METHODS: Forty-nine ECs (three tumour blocks/case) were selected with alterations
in POLE (n=10), CTNNB1 (n=8), p53 (n=10), mismatch repair (n=11), L1CAM (n=10),
and ECs without any of these markers (n=9). Nine ECs carried more than one
molecular marker. All 147 blocks were analysed for POLE exonuclease domain and
CTNNB1 exon 3 mutations, and for p53, mismatch repair and L1CAM protein
expression. All blocks were assigned to a favourable, intermediate or
unfavourable risk group, based on a molecular risk assignment. RESULTS:
Concordance between the three tumour blocks for POLE and CTNNB1 mutational
status, and p53, mismatch repair and L1CAM protein expression was found in 100%
(48/48), 95.9% (47/49), 93.9% (46/49), 98.0% (48/49), and 91.8% (45/49) of
tumours, respectively. These discordances were found in a total of nine cases
(18.4%). The intratumour heterogeneity impacted the risk assignment in five cases
(10.2%). CONCLUSION: Intratumour heterogeneity of prognostic molecular markers in
EC without morphologic heterogeneity is uncommon among three tumour fractions,
affecting the molecular risk allocation in a limited number of cases. This low
intratumour heterogeneity facilitates the implementation of the molecular risk
assignment, advocating its use in clinical decision making.
PMID- 28424423
TI - The antidepressant-like effect of trans-astaxanthin involves the serotonergic
system.
AB - The antidepressant-like effect of trans-astaxanthin, a compound present rich in
algae, was evaluated through behavioral and neurochemical methods. Results showed
that trans-astaxanthin treatment significantly decreased the immobility time in
force swim test and tail suspension test, but did not influence locomotor
activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia
and ptosis induced by reserpine. However, pre-treatment with para
chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in
force swim and tail suspension test. These results suggested that the mechanism
of antidepressant-like effect of trans-astaxanthin may involve the serotonergic
system, but not noradrenaline system. This hypothesis was confirmed by
neurochemical assays which showed that trans-astaxanthin increased serotonin
levels in the hippocampus, frontal cortex, striatum and hypothalamus.
Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3
dioxygenase activity in the hippocampus, frontal cortex and hypothalamus.
Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the
kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these
brain regions. Taken together, these findings indicate that the antidepressant
like effect of trans-astaxanthin involves the serotonergic system.
PMID- 28424424
TI - Leukocyte telomere length-related genetic variants in ACYP2 contribute to the
risk of esophageal carcinoma in Chinese Han population.
AB - BACKGROUND: Short leukocyte telomere length has been associated with
significantly increased risk of esophageal carcinoma. A previous genome-wide
association study demonstrated that ACYP2 was associated with leukocyte telomere
length. However, the role of ACYP2 genetic variants on esophageal carcinoma
susceptibility is still unknown. Therefore, we investigated whether ACYP2
polymorphisms have impact on the risk of esophageal carcinoma in Chinese.
MATERIALS AND METHODS: We conducted a case-control study among 386 cases and 495
healthy controls from northwest China. 14 SNPs in ACYP2 were selected and
genotyped using Sequenom MassARRAY technology. Odds ratios (OR) and 95%
confidence intervals (CIs) were calculated by unconditional logistic regression
adjusting for age and gender. RESULTS: We found that 1.34-fold increased risk of
esophageal carcinoma is associated with the rs11125529 A allele compared with the
rs11125529 C allele (OR=1.29, 95%CI: 1.02-1.62, p=0.030) under the additive
model, after adjusted by age and gender. We also found rs11896604 and rs17045754
loci increased the esophageal carcinoma risk under the additive model
(rs11896604: OR=1.34, 95%CI: 1.03-1.76, p=0.032; rs17045754: OR=1.36, 95%CI: 1.03
1.80, p=0.028). One main linkage block was observed across the locus. This block
was comprised of seven closely linked SNPs: rs1682111, rs843752, rs10439478,
rs843645, rs11125529, rs843711 and rs11896604. The haplotype analysis detected
that haplotype "TTCTATG" increased the risk of esophageal carcinoma (OR=1.38,
95%CI: 1.04-1.82, p=0.025). CONCLUSION: In conclusion, ACYP2 gene may be
associated with an increased risk of esophageal carcinoma in Chinese Han
populations. Future studies to address the biological function of this
polymorphism in the development of esophageal carcinoma are warranted.
PMID- 28424426
TI - Circular RNA hsa-circ-0016347 promotes proliferation, invasion and metastasis of
osteosarcoma cells.
AB - Circular RNAs (circRNAs) are a novel class of non-coding RNA which have recently
shown huge capabilities in the regulation of gene expression at the post
transcriptional level. Growing evidence has indicated that circRNAs could serve
as competing endogenous RNAs (ceRNAs) to bind with microRNAs (miRNAs) and to
inhibit the activity and function of the targeted miRNAs. Here, we demonstrated
that circ-0016347 acted as a positive regulator in osteosarcoma cells
proliferation and invasion. Moreover, circ-0016347 was identified as a sponge of
miR-214 that upregulated the expression of caspase-1, which is the functional
target of miR-214. Our study provides novel insight into the regulatory mechanism
of circ-0016347 and its downstream targets in proliferation, invasion and
metastasis of osteosarcoma cells, which will facilitate further development in
the therapy of osteosarcoma.
PMID- 28424427
TI - NOS2 expression in glioma cell lines and glioma primary cell cultures:
correlation with neurosphere generation and SOX-2 expression.
AB - Nitric oxide has been implicated in biology and progression of glioblastoma (GBM)
being able to influence the cellular signal depending on the concentration and
duration of cell exposure. NOS2 (inducible nitric oxide synthase) have been
proposed as a component of molecular profile of several tumors, including glioma,
one of the most aggressive primary brain tumor featuring local cancer stem cells
responsible for enhanced resistance to therapies and for tumor recurrence. Here,
we investigated the NOS2 mRNA expression by reverse transcription-PCR in human
glioma primary cultures at several grade of malignancy and glioma stem cell (GSC)
derived neurospheres. Glioma cell lines were used as positive controls both in
terms of stemness marker expression that of capacity of generating neurospheres.
NOS2 expression was detected at basal levels in cell lines and primary cultures
and appeared significantly up-regulated in cultures kept in the specific medium
for neurospheres. The immunofluorescence analysis of all cell cultures to
evaluate the levels of SOX-2, a stemness marker aberrantly up-regulated in GBM,
was also performed. The potential correlation between NOS2 expression and ability
to generate neurospheres and between NOS2 and SOX-2 levels was also verified. The
results show that the higher NOS2 expression is detected in all primary cultures
able to arise neurosphere. A high and significant correlation between NOS2
expression and SOX-2 positive cells (%) in all cell cultures maintained in
standard conditions has been observed. The results shed light on the potential
relevance of NOS2 as a prognostic factor for glioma malignancy and recurrence.
PMID- 28424429
TI - The volatile molecule signature of four mycobacteria species.
AB - Mycobacteria are the leading cause of death from infectious disease worldwide and
limitations in current diagnostics are hampering control efforts. In recent
years, the use of small volatile molecules as diagnostic biomarkers for
mycobacteria has shown promise for use in the rapid analysis of in vitro cultures
as well as ex vivo diagnosis using breath or sputum. In this study, 18 strains
from four mycobacteria species (Mycobacterium avium, M. bovis BCG, M.
intracellulare and M. xenopi) were analyzed for the first time using two
dimensional gas chromatography time-of-flight mass spectrometry (GC * GC-TOFMS).
This study represents the first time volatile molecules associated with M.
intracellulare and M. xenopi have ever been reported. A total of 217
chromatographic features were identified and 58 features were selected that
discriminate between these four species. Putative identifications are provided
for 17 of the 58 discriminatory features, three of which have been reported
previously in mycobacteria. The identification of mycobacteria-associated
volatile biomarker suites could reduce the time-to-diagnosis for mycobacterial
infections, either from in vitro cultures prior to the visualization of colonies
or directly from ex vivo specimens, thereby shortening the empiric treatment
window and potentially improving outcomes.
PMID- 28424428
TI - Global miRNA expression profiling of domestic cat livers following acute
Toxoplasma gondii infection.
AB - Although microRNAs (miRNAs) play an important role in liver homeostasis, the
extent to which they can be altered by Toxoplasma gondii infection is unknown.
Here, we utilized small RNA sequencing and bioinformatic analyses to characterize
miRNA expression profiles in the liver of domestic cats at 7 days after oral
infection with T. gondii (Type II) strain. A total of 384 miRNAs were identified
and 82 were differentially expressed, of which 33 were up-regulated and 49 down
regulated. Also, 5690 predicted host gene targets for the differentially
expressed miRNAs were identified using the bioinformatic algorithm miRanda. Gene
ontology analysis revealed that the predicted gene targets of the dysregulated
miRNAs were significantly enriched in apoptosis. Kyoto Encyclopedia of Genes and
Genomes analysis showed that the predicted gene targets were involved in several
pathways, including acute myeloid leukemia, central carbon metabolism in cancer,
choline metabolism in cancer, estrogen signaling pathway, fatty acid degradation,
lysosome, nucleotide excision repair, progesterone-mediated oocyte maturation,
and VEGF signaling pathway. The expression level of 6 upregulated miRNAs (mmu-miR
21a-5p, mmu-miR-20a-5p, mmu-miR-17-5p, mmu-miR-30e-3p, mmu-miR-142a-3p, and mmu
miR-106b-3p) was confirmed by stem-loop quantitative reverse transcription PCR,
which yielded results consistent with the sequencing data. These findings expand
our understanding of the regulatory mechanisms of miRNAs underlying T. gondii
pathogenesis and contribute new database information on cat miRNAs, opening a new
perspective on the prevention and treatment of T. gondii infection.
PMID- 28424430
TI - Exploring non-stationarity patterns in schizophrenia: neural reorganization
abnormalities in the alpha band.
AB - OBJECTIVE: The aim of this paper was to characterize brain non-stationarity
during an auditory oddball task in schizophrenia (SCH). The level of non
stationarity was measured in the baseline and response windows of relevant tones
in SCH patients and healthy controls. APPROACH: Event-related potentials were
recorded from 28 SCH patients and 51 controls. Non-stationarity was estimated in
the conventional electroencephalography frequency bands by means of Kullback
Leibler divergence (KLD). Relative power (RP) was also computed to assess a
possible complementarity with KLD. MAIN RESULTS: Results showed a widespread
statistically significant increase in the level of non-stationarity from baseline
to response in all frequency bands for both groups. Statistically significant
differences in non-stationarity were found between SCH patients and controls in
beta-2 and in the alpha band. SCH patients showed more non-stationarity in the
left parieto-occipital region during the baseline window in the beta-2 band. A
leave-one-out cross validation classification study with feature selection based
on binary stepwise logistic regression to discriminate between SCH patients and
controls provided a positive predictive value of 72.73% and negative predictive
value of 78.95%. SIGNIFICANCE: KLD can characterize transient neural
reorganization during an attentional task in response to novelty and relevance.
Our findings suggest anomalous reorganization of neural dynamics in SCH during an
oddball task. The abnormal frequency-dependent modulation found in SCH patients
during relevant tones is in agreement with the hypothesis of aberrant salience
detection in SCH. The increase in non-stationarity in the alpha band during the
active task supports the notion that this band is involved in top-down
processing. The baseline differences in the beta-2 band suggest that
hyperactivation of the default mode network during attention tasks may be related
to SCH symptoms. Furthermore, the classification improved when features from both
KLD and RP were used, supporting the idea that these measures can be
complementary.
PMID- 28424431
TI - [2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: What is new?]
PMID- 28424432
TI - [Prevalence of HIV infection in Turkey and importance of cardiovascular disease].
PMID- 28424433
TI - [Investigating the role of ceramide metabolism-associated CERS5 (LASS5) gene in
atherosclerosis pathogenesis in endothelial cells].
AB - OBJECTIVE: Ceramide, the backbone of sphingolipids, is the key component
affecting atherosclerotic changes through its important second-messenger role.
Previous studies have demonstrated protective role of AMP-activated protein
kinase (AMPK) genes in regulating atherosclerosis and hypertension. Ceramide
synthase 5 (LASS5 or CERS5) gene has function in de novo synthesis of ceramide,
and has indirect effect on AMPK gene. Aim of the present study was to identify
role of LASS5 gene in atherosclerosis. METHODS: LASS5 gene-specific small
interfering RNA (siRNA)-mediated gene silencing was performed in human umbilical
vein endothelial cells (HUVEC) and differential expression of LASS5, AMPK-alpha
and AMPK-alpha target genes were analyzed. HUVEC cells were then treated with
AMPK activator in order to examine relationship of change in gene expression
levels to AMPK activity. RESULTS: Novel physiological function of LASS5 was
identified. Downregulation of LASS5 was found to attenuate ceramide production
and increase expression of some AMPK target genes in HUVEC. CONCLUSION: This is
the first study to demonstrate that LASS5 was involved in negative regulation of
atherosclerosis-related genes, such as AMPK-alpha. These preliminary findings
provide insight into molecular mechanism of atherosclerosis and are important for
development of potential therapeutic agents in the treatment of atherosclerosis.
PMID- 28424434
TI - High-dose bolus tirofiban versus low-dose bolus in patients with acute coronary
syndrome undergoing percutaneous coronary intervention.
AB - OBJECTIVE: Aim of the present study was to determine effects of high-dose versus
low-dose intravenous (IV) bolus tirofiban on angiographic measures, ST
resolution, enzymatic infarct size, and clinical outcomes in patients with acute
coronary syndrome (ACS) who were undergoing percutaneous coronary intervention
(PCI) and received current pharmacoinvasive therapy. METHODS: Acute coronary
syndrome patients (n=271, 85.6% male; mean age: 57.9+/-12.6 years) from between
2009 and 2015 who received IV tirofiban therapy following PCI were
retrospectively analyzed. All patients had received maintenance tirofiban
infusion (0.15 ug/kg/min) after bolus dose and 600 mg clopidogrel. Percentage of
patients undergoing drug eluting stent implantation procedure was 33.5%.
Tirofiban was administered to all patients in bailout situation or for thrombotic
complication after PCI. RESULTS: High-dose IV bolus group (25 ug/kg; n=140) was
associated with greater ST segment resolution (66% vs. 50%, p=0.013) and reduced
peak troponin release [12.4 ng/dL (range: 6.5-21.5 ng/dL) vs. 16.4 ng/dL (range:
10.1-27.4 ng/dL), p=0.001] compared with low-dose bolus group (10 ug/kg, n=131).
Cardiovascular event rates were similar between groups at in-hospital, 1-month,
and 6-month follow-up (p=1.000, 1.000, and 0.287, respectively). Percentage of
patients with post-procedural Thrombolysis in Myocardial Infarction (TIMI) grade
III flow, major, and minor bleeding were similar (p=0.085, 1.000, and 0.965,
respectively). CONCLUSION: Use of high-dose IV bolus tirofiban in addition to
aspirin and high-dose clopidogrel improves ST segment resolution, reduces infarct
size, and does not increase bleeding events in patients with ACS undergoing PCI
compared with low-dose bolus. Angiographic measures and clinical endpoints were
similar between groups.
PMID- 28424435
TI - [EUROASPIRE-IV: European Society of Cardiology study of lifestyle, risk factors,
and treatment approaches in patients with coronary artery disease: Data from
Turkey].
AB - OBJECTIVE: Data from EUROASPIRE-IV Turkey report investigating risk factors and
adherence to guidelines in patients hospitalized for coronary artery disease are
presented and results are compared with those of EUROASPIRE-III Turkey and
EUROASPIRE-IV Europe. METHODS: Study was performed in 24 European countries,
including Turkey (17 centers). Patients (18-80 years old) hospitalized for
coronary (index) event during preceding 3 years were identified from hospital
records and interviewed >=6 months later. Patient information regarding index
event was acquired from hospital records. Anamnesis was obtained during the
interview, and physical examination and laboratory analyses were performed.
RESULTS: Median age at the index coronary event was 58.8 years, and it was
significantly decreased compared with last EUROASPIRE-III study (60.5 years),
which was conducted at the same centers 6 years earlier (p=0.017). Of all
patients, 19.3% were under 50 years of age and mean age was lower than that of
EUROASPIRE-IV Europe (62.5 years). Comparing EUROASPIRE-IV Turkey with EUROASPIRE
III Turkey, rate of smokers increased to 25.5% from 23.1% (p=0.499), obesity
increased to 40.7% from 35.5% (p=0.211), total cholesterol level increased to
49.6% from 48.3% (p=0.767), and diabetes rate increased to 39.7% from 33.6%
(p=0.139), however none of the differences reached a level of statistical
significance. Only 11.7% of the smokers quit after coronary event. Rates for
these factors were lower in EUROASPIRE-IV Europe (16% for smoking, 37.6% for
obesity, and 26.8% for diabetes). CONCLUSION: EUROASPIRE-IV Turkey data revealed
that secondary prevention was unsatisfactory and had progressed unfavorably
compared with last EUROASPIRE study, some risk factors were more uncontrolled
than overall European average, and coronary artery events at young age remain an
important problem.
PMID- 28424436
TI - [Dyslipidemia and cardiovascular risk assessment in HIV-positive patients].
AB - OBJECTIVE: Dyslipidemia is a major complication of antiretroviral treatment. Aim
of the present study was to screen baseline lipid levels and cardiovascular
disease risk in HIV-positive patients and analyze change in those parameters
after initiation of antiretroviral treatment (ART). METHODS: HIV-positive
patients who presented at our clinic between April 2011 and August 2012 were
included. Study included 19 female (22.1%) and 67 male (77.9%) patients (mean age
39.5+/-10.3 years). Blood pressure, smoking habit, alcohol consumption, serum
total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low
density lipoprotein (LDL), glucose level, and antiretroviral treatment status
data were reviewed retrospectively. Changes in lipid profile and lifetime risk
for atherosclerotic cardiovascular disease (ASCVD) according to the American
College of Cardiology guidelines were compared with baseline data and analyzed.
RESULTS: At baseline, 13 (15.1%) patients were already receiving ART and 73
(84.9%) patients were treatment-naive or had stopped therapy >=3 months prior to
enrollment. At last visit, 73 (84.9%) patients were taking ART. Results of
baseline and final visit TC levels were 175.5 mg/dL (range: 90-346 mg/dL) and
196.5 mg/dL (range: 104-317 mg/dL), respectively (p=0.001). HDL levels were 40
mg/dL (range: 21-81 mg/dL) and 35 mg/dL (range: 10-75 mg/dL; p=0.001), and LDL
levels were 101.5 mg/dL (range: 32-191 mg/dL) and 120.5 mg/dL (range: 32-250
mg/dL; p<0.001). TG levels were 145.5 mg/dL (range: 43-2580 mg/dL and 152.5 mg/dL
(range: 67-884 mg/dL; p=0.102). Baseline ASCVD risk score was 46% (range: 5-69%)
while last visit ASCVD risk score was 50% (range: 5-69%; p<0.001). CONCLUSION:
HIV infection has adverse effects on lipid profiles and cardiovascular risk of
HIV-positive patients. Therefore, patients should be closely monitored for
lifestyle interventions and lipid-lowering agents.
PMID- 28424437
TI - [The effects of coronary artery disease severity on left atrial deformation
parameters in patients with stable coronary artery disease].
AB - OBJECTIVES: Aim of the present study was to investigate correlation between left
atrial (LA) deformation parameters assessed using 2-dimensional (2D) speckle
tracking echocardiography (STE) and complexity of coronary artery disease
according to SYNTAX score (SXscore) in patients with stable coronary artery
disease (SCAD). STUDY DESIGN: Total of 60 moderate-risk SCAD patients (40 men, 20
women) who underwent coronary angiography and 30 healthy controls were included.
Measurements of conventional echocardiographic parameters as well as peak LA
strain during ventricular systole (LA-RES), peak LA strain during atrial systole
(LA-PUMP), peak LA strain rate during ventricular systole (LA-SRS), peak LA
strain rate during early diastole (LA-SRE), and peak LA strain rate during atrial
systole (LA-SRA) were obtained. RESULTS: Patients were categorized into 2 groups:
low SXscore of <20 (Group I) and high SXscore of >=20 (Group II). Left
ventricular (LV) diastolic functions were significantly impaired and LV filling
pressure was significantly higher in high SXscore group. LA-RES (Control Group:
42.3+/-7.9, Group I: 36.4+/-8.2, Group II: 27.5+/-8.1; p<0.001) and LA-PUMP
(Control Group: 17.6+/-3.4, Group I: 15.7+/-2.5, Group II: 13.1+/-3.2; p<0.001)
were significantly lower in high SXscore group compared with low SXscore group.
There was no statistical difference in LA-SRS, LA-SRE, or LA-SRA between the 3
groups. Correlation analysis indicated negative correlation between SXscore level
and LA-RES function (r=-0.49; p<0.001). CONCLUSION: 2D-STE-based LA deformation
parameters are significantly impaired in patients with SCAD who have high
SXscore. In addition, evaluation of LA-RES and LA-PUMP functions might be useful
in estimating severity of disease in patients with SCAD.
PMID- 28424438
TI - Using cardiovascular imaging modalities to determine cardiac disorders before
starting sports activities.
AB - OBJECTIVE: We re-examined children who had previously been declared eligible to
participate in competitive sports activities for cardiac disorders, using cardiac
investigation protocol. METHODS: Total of 250 children (224 males [89.6%], and 26
females [10.4%]) between the ages of 8 and 17 years who had just started or were
already engaged in sports activities were included in the study. Participants had
detailed physical examination evaluated by a pediatric cardiologist. Those with
findings suggesting cardiac disorder in their history and/or physical
examinations, and/or 12-channel electrocardiography (ECG) were examined with
echocardiography (ECHO), 24-hour Holter monitoring, and exercise test. RESULTS:
Mean duration of participation in sports activities was 13 months. Among all,
10.4% of the children had abnormalities on ECG. ECHO demonstrated cardiomyopathy
in 1, mitral valve prolapse in 2, tricuspid insufficiency in 2, and mitral
insufficiency in 1 participant. Holter monitoring revealed non-sustained
ventricular tachycardia attacks in 1, and supraventricular tachycardia in another
child. Three were ultimately disqualified from partaking in competitive sports.
CONCLUSION: Sports and medical communities must work together to establish study
protocols to prevent sudden death related to sports and to make these activities
safer for athletes. Pediatric cardiology consultation for young athletes before
they start sports activities is needed.
PMID- 28424439
TI - Management of immediate partial bioresorbable vascular scaffold stent thrombosis.
AB - Bioresorbable vascular scaffold (BVS) stents have been proposed recently as an
elegant technique for treatment of coronary artery disease. However, perspective
that these "dissolvable" stents will replace conventional metallic stents in
broad spectrum of clinical conditions and patient categories in the near future
has been moderated by non-negligible incidence of stent thrombosis (ST).
Mechanical factors, such as strut thickness and malapposition have been
implicated in increased risk of BVS ST. Presently described is case of immediate
partial BVS ST in a young male related to technical procedural problem, rather
than mechanical problem. Glycoprotein IIb/IIIa inhibitors associated with
anticoagulation resulted in complete resolution of thrombus and facilitated
successful patient outcome.
PMID- 28424440
TI - Gemcitabine-induced coronary vasospasm: A case report.
AB - Gemcitabine is a chemotherapy drug. It is a nucleoside analogue that is usually
well tolerated by patients, with myelosuppression (especially thrombocytopenia)
as dose-limiting side effect. Other mild to moderate side effects include
alopecia, vomiting, nausea, rash, and fever. Coronary ischemia is the most common
cardiotoxic effect of gemcitabine, which is due to its antimetabolites. While
underlying cause of coronary ischemia following use of gemcitabine is uncertain,
endothelial dysfunction and coronary thrombosis are potential explanations. To
our knowledge, there are few published case reports of adverse cardiovascular
side effects associated with gemcitabine. Presently described is case of acute
inferior myocardial infarction in a female patient caused by gemcitabine.
PMID- 28424441
TI - Spontaneous echocardiographic contrast due to ductus venosus.
AB - Spontaneous echocardiographic contrast is defined as a phenomenon of discrete
reflections appearing in the cardiac chambers or great vessels. It has been
associated with several conditions leading to microbubble formation or low blood
flow. This is a report of a neonate with spontaneous echocardiographic contrast
related to patent ductus venosus.
PMID- 28424442
TI - Clinical improvement and no further need of transplant after closure of PDA with
transcatheter approach in an end-stage heart failure patient with
hypertrabeculation.
AB - Although heart failure is managed medically most of the time, heart
transplantation is still last resort for selected end-stage heart failure
patients with noncompaction cardiomyopathy. Presently described for the first
time is case of pediatric patient with noncompaction cardiomyopathy who was
initially referred to our hospital for heart transplant but underwent PDA repair
and improved clinically without need for heart transplant.
PMID- 28424443
TI - Case report of a rarely seen long-segment middle aortic syndrome.
AB - Middle aortic syndrome (MAS) follows a course with distal thoracic and abdominal
aorta stenosis. It is a rare disease that is usually diagnosed after the first
decade of life. Clinical reflection of MAS is often in the form of hypertension
and claudication in the lower extremities. Its etiology is unclear, but is known
to be associated with congenital or acquired diseases. This pathology, which is
accompanied by malignant hypertension, often does not respond to medical
treatment. In patients with MAS, surgical treatment is first line recommendation
to prevent complications such as hypertension, heart failure, intracranial
bleeding, or aortic rupture. In order to draw attention to this disease,
presently described is case of high blood pressure detected during routine
examination of a child who had no complaint, and discovery of long-segment
stenosis in the abdominal aorta identified with echocardiography and conventional
angiography.
PMID- 28424444
TI - A successful cesarean delivery without fetal or maternal morbidity in an
Eisenmenger patient with cor triatriatum sinistrum, double-orifice mitral valve,
large ventricular septal defect, and single ventricle who was under long-term
bosentan treatment.
AB - Presently described is successful cesarean delivery in a pregnancy superimposed
on long-term bosentan treatment in an Eisenmenger syndrome patient with cor
triatriatum sinistrum, double-orifice mitral valve, and large ventricular septal
defect resulting in single functioning ventricle with double outlets. Cesarean
delivery was performed at 27th week of gestation without maternal or fetal
morbidity. The infant had no congenital cardiovascular abnormality or any
probable teratogenic effect of bosentan treatment during pregnancy.
PMID- 28424445
TI - Management of tachyarrhythmia during pregnancy.
AB - Maternal tachyarrhythmia is a common complication during pregnancy due to
hormonal changes that enhance pre-existing arrhythmias or induce new arrhythmias
in the presence of congenital heart defects in pregnant females. Presence of
tachyarrhythmia during pregnancy poses risk to the mother and fetus, calling for
proper treatment with medications. Use of antiarrhythmic drugs in cases of
maternal tachyarrhythmia must give due consideration of potential teratogenic
side effects. Utilization of antiarrhythmic drugs during pregnancy has been well
studied; some result in minimal fetal harm or none at all. New techniques, such
as cardiac ablation, have also been implemented with minimal or no radiation
exposure to the fetus or mother. Pregnant women with tachyarrhythmia have been
successfully treated with little to no impact on the developing fetus as result
of increasing experience with antiarrhythmic drugs and progress of new procedural
techniques.
PMID- 28424446
TI - Speckle tracking strain imaging: Practical approach for application.
PMID- 28424447
TI - Case images: Detection and management of ICD lead implanted in middle cardiac
vein.
PMID- 28424448
TI - Case images: Treatment of thrombotic subclavian artery stenosis involving
vertebral artery ostium with maximum protection.
PMID- 28424449
TI - Case images: Electrical isolation of superior vena cava as well as pulmonary vein
isolation with cryoballoon technique in a young patient with persistent atrial
fibrillation.
PMID- 28424450
TI - Case images: A rare complication of infective endocarditis: Ruptured
pseudoaneurysm of mitral-aortic interventricular fibrosa.
PMID- 28424451
TI - Prognostic impact of NOTCH1, MYD88, and SF3B1 mutations in Polish patients with
chronic lymphocytic leukemia.
AB - INTRODUCTION Currently available prognostic factors determining the course of
chronic lymphocytic leukemia (CLL) are not fully efficient, especially for newly
diagnosed patients. Investigation of molecular changes may help clarify the
reasons for the heterogeneity of the disease. Apart from already confirmed TP53
mutations, the novel candidates: NOTCH1, SF3B1, and MYD88 might represent
clinically relevant biomarkers. OBJECTIVES The aim of this study was to
evaluate the mutational status of NOTCH1, MYD88, and SF3B1 and to compare the
results with confirmed prognostic factors: ZAP-70, CD38, and immunoglobulin heavy
chain variable region (IGHV) mutation in CLL. The study assessed also prognostic
significance in terms of the time to first treatment (TTFT) and subset analysis.
PATIENTS AND METHODS The study was conducted on samples of 370 newly diagnosed
patients with CLL. The analysis was performed using high-resolution melting,
Sanger sequencing, and polymerase chain reaction methods. RESULTS Patients
harboring the NOTCH1 mutation were significantly more often found among patients
with an unmutated IGHV gene status and high expression of CD38 and ZAP-70. The
MYD88 mutation was equally distributed in patients with mutated and unmutated
IGHV status (5 vs 7 patients). For MYD88 and SF3B1, there were no significant
differences in the levels of CD38 and ZAP-70 expression. The tendency for lower
median TTFT was revealed in patients with mutated SF3B1 (P = 0.08). The analysis
showed the presence of 14 different types of the subsets of IGHV in 50 of 345
patients (14.5%). The most frequent were subsets #1 and #2. CONCLUSIONS The
NOTCH1 and SF3B1 mutations accompany biological markers of unfavorable prognosis
in patients with CLL. The mutations may contribute to the identification of
patients with high-risk CLL.
PMID- 28424452
TI - Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C
Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined
Signaling Route Would Induce Alternative Consideration to Previous Conceptions.
AB - BACKGROUND Parathyroid hormone (PTH) is an effective anti-osteoporosis agent,
after binding to its receptor PTHR1, several signaling pathways, including
cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are
initiated through G proteins; with the cAMP/PKA pathway as the major pathway.
Earlier studies have reported that PTHR1 might also activate PKC via a PLC
independent mechanism, but this pathway remains unclear. MATERIAL AND METHODS In
HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with
fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In
MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then
assays for cell apoptosis, cell differentiation, alkaline phosphatase activity,
and mineralization were performed. RESULTS The FRET analysis found that PTH(1
34), [G1,R19]PTH(1-34) (GR(1-34), and [G1,R19]PTH(1-28) (GR(1-28) were all
activated by PKC. The PKC activation ability of GR(1-28) was blocked by cAMP
inhibitor (Rp-cAMP) and rescued with the addition of active PKA-alpha and PKA
beta. The PKC activation ability of GR(1-34) was partially inhibited by Rp-cAMP.
In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was
regulated by GR(1-28) were significantly changed by the pan-PKC inhibitor Go6983.
After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG
were differentially regulated by GR(1-28) or GR(1-34), and the difference was
blunted by Go6983. PTH(1-34), GR(1-28), and GR(1-34) significantly decreased
early apoptosis and augmented osteoblastic differentiation in accordance with the
activities of PKA and PKC. CONCLUSIONS PLC-independent PKC activation induced by
PTH could be divided into two potential mechanisms: one was PKA-dependent and
associated with PTH(1-28); the other was PKA-independent and associated with
PTH(29-34). We also found that PTH could activate PLC-independent PKC via PKA
dependent mechanisms.
PMID- 28424453
TI - Comorbid Human Immunodeficiency Virus (HIV) and Muscle-Specific Kinase (MuSK)
Myasthenia Gravis: A Case Report and Literature Review.
AB - BACKGROUND HIV infections with concomitant immunologically-mediated disorders
have been frequently described but there has been little research on the
association between HIV and myasthenia gravis. MuSK myasthenia gravis coexisting
with HIV is an even a rarer entity and can occur as a part of immune restoration
disease. We report the case of a patient with asymptomatic HIV infection who
presented with new-onset MuSK myasthenia gravis. CASE REPORT A 44-year-old
African-American woman with HIV since 2004 and on highly active antiretroviral
therapy (HAART) presented to the ED with complains of double vision and
difficulty swallowing for 2 weeks. The patient was intermittently on HAART
therapy. On examination, she had bilateral ptosis, weak orbicularis oris and
orbicularis oculi, along with mild lateral gaze palsy of the left eye. Her CD4
count was 383 and the viral load was undetectable. An MRI of the brain produced
normal results and a CT chest did not show thymus enlargement. Due to worsening
symptoms and high suspicion for myasthenia gravis, she was started on IVIG at 0.4
mg/kg/day for 5 days, and her symptoms markedly improved. She was found to have
strongly positive MuSK antibody and negative Ach receptor antibody. Repetitive
nerve stimulation showed a 13% decrease in the right median nerve, which
confirmed the diagnosis. She was subsequently discharged to home on
pyridostigmine. Azathioprine was added at clinic follow-up. The patient continues
to improve. CONCLUSIONS As the use of antiretroviral therapy increases, immune
reconstitution syndromes have become more common. Rare associations like HIV and
MuSK myasthenia gravis are being increasingly reported. The use of
immunosuppressants in the treatment of these conditions should be carefully
evaluated.
PMID- 28424454
TI - Inference of the infection status of individuals using longitudinal testing data
from cryptic populations: Towards a probabilistic approach to diagnosis.
AB - Effective control of many diseases requires the accurate detection of infected
individuals. Confidently ascertaining whether an individual is infected can be
challenging when diagnostic tests are imperfect and when some individuals go for
long periods of time without being observed or sampled. Here, we use a multi
event capture-recapture approach to model imperfect observations of true
epidemiological states. We describe a method for interpreting potentially
disparate results from individuals sampled multiple times over an extended
period, using empirical data from a wild badger population naturally infected
with Mycobacterium bovis as an example. We examine the effect of sex, capture
history and current and historical diagnostic test results on the probability of
being truly infected, given any combination of diagnostic test results. In doing
so, we move diagnosis away from the traditional binary classification of
apparently infected versus uninfected to a probability-based interpretation which
is updated each time an individual is re-sampled. Our findings identified
temporal variation in infection status and suggest that capture probability is
influenced by year, season and infection status. This novel approach to combining
ecological and epidemiological data may aid disease management decision-making by
providing a framework for the integration of multiple diagnostic test data with
other information.
PMID- 28424455
TI - Flow virometry analysis of envelope glycoprotein conformations on individual HIV
virions.
AB - HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a
correct trimeric conformation, Env mediates virus-cell binding and fusion.
Malfunctioning of this machinery renders virions incapable of infecting cells.
Each HIV-1 virion carries 10-14 Envs, and therefore a defective Env may not
necessarily render a HIV virion non-infectious, since other Env on the same
virion may still be functional. Alternatively, it is possible that on a given
virion either all the spikes are defective or all are functional. Here, we
investigate Env conformations on individual virions using our new nanotechnology,
"flow virometry", and a panel of antibodies that discriminate between various Env
conformations. We found that the majority of HIV-1 virions carry either only
trimeric ("functional") or only defective spikes. The relatively small
subfraction of virions that carry both functional and nonfunctional Envs
contributes little to HIV infection of human lymphoid tissue ex vivo. The
observation that the majority of virions exclusively express either functional or
nonfunctional forms of Env has important implications for understanding the role
of neutralizing and non-neutralizing antibodies in the immune control of HIV
infection as well as for the development of effective prophylactic strategies.
PMID- 28424456
TI - Paraquat poisoning induced pulmonary epithelial mesenchymal transition through
Notch1 pathway.
AB - Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ
poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved
in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch
signaling is required for EMT. In this study, we investigated whether Notch1 and
TGF-beta1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated
that A549 cells underwent EMT after treated with PQ at dose of 300 MUmol/L for 6
days, charactered by increasing expression of mesenchymal marker alpha-SMA and
decreasing expression of epithelial marker E-cadherin. We found that there was an
apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process.
EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a
gamma-secretase inhibitor. Our data also showed that the expression of TGF
beta1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1
significantly induced SMA expression, and this induction was completely inhibited
by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was
important in EMT induced by PQ, and TGF-beta1/Smad3 signaling partly plays a role
as the downstream of Notch1.
PMID- 28424457
TI - Vertex coloring of graphs via phase dynamics of coupled oscillatory networks.
AB - While Boolean logic has been the backbone of digital information processing,
there exist classes of computationally hard problems wherein this paradigm is
fundamentally inefficient. Vertex coloring of graphs, belonging to the class of
combinatorial optimization, represents one such problem. It is well studied for
its applications in data sciences, life sciences, social sciences and technology,
and hence, motivates alternate, more efficient non-Boolean pathways towards its
solution. Here we demonstrate a coupled relaxation oscillator based dynamical
system that exploits insulator-metal transition in Vanadium Dioxide (VO2) to
efficiently solve vertex coloring of graphs. Pairwise coupled VO2 oscillator
circuits have been analyzed before for basic computing operations, but using
complex networks of VO2 oscillators, or any other oscillators, for more complex
tasks have been challenging in theory as well as in experiments. The proposed VO2
oscillator network harnesses the natural analogue between optimization problems
and energy minimization processes in highly parallel, interconnected dynamical
systems to approximate optimal coloring of graphs. We further indicate a
fundamental connection between spectral properties of linear dynamical systems
and spectral algorithms for graph coloring. Our work not only elucidates a
physics-based computing approach but also presents tantalizing opportunities for
building customized analog co-processors for solving hard problems efficiently.
PMID- 28424458
TI - Light penetration-coupled photoisomerization modeling for photodeformation of
diarylethene single crystal: upscaling isomerization to macroscopic deformation.
AB - Diarylethene is one of the photo-responsive materials that show rapid and
reversible changes in their color/electrochemical properties and macroscopic
deformations in the crystalline phase by light irradiation. Photoisomerization is
the main cause of the photo reactivity of diarylethene, and we established a
statistical model based on the density matrix formalism, which predicts
quantitative isomerization progress as a population term. The model reflects
photo-switching properties of the target molecule, which were characterized by
first principle calculations, and external stimulus factors (light irradiation
conditions and temperature). By merging light penetration physics with the model,
we derived light penetration depth dependent isomerization progress to
theoretically investigate photodeformation of single crystal. The model well
reproduced in-plane shear deformation under ultraviolet light irradiation which
would provide guideline for photoactuator design. In addition, the statistical
model addressed crucial findings (primary stimuli and molecular design parameter
for increasing the isomerization rate, external stimuli enhancing fluorescence
performance) itself.
PMID- 28424459
TI - Development and outcomes of a primary care-based sleep assessment service in
Canterbury, New Zealand.
AB - : Prior to 2007, increasing demand for sleep services, plus inability to
adequately triage severity, led to long delays in sleep assessment and accessing
continuous positive airway pressure. We established a community sleep assessment
service carried out by trained general practices using a standardised tool and
overnight oximetry. All cases were discussed at a multi-disciplinary meeting,
with four outcomes: severe obstructive sleep apnoea treated with continuous
positive airway pressure; investigation with more complex studies; sleep
physician appointment; no or non-severe sleep disorder for general practitioner
management. Assessment numbers increased steadily (~400 in 2007 vs. 1400 in
2015). Median time from referral to assessment and multi-disciplinary meeting was
28 and 48 days, respectively. After the first multi-disciplinary meeting, 23% of
cases were assessed as having severe obstructive sleep apnoea. More complex
studies (mostly flow based) were required in 49% of patients, identifying severe
obstructive sleep apnoea in a further 13%. Thirty-seven percent of patients had
obstructive sleep apnoea severe enough to qualify for funded treatment. Forty
eight percent of patients received a definitive answer from the first multi
disciplinary meeting. Median time from referral to continuous positive airway
pressure for 'at risk' patients with severe obstructive sleep apnoea, e.g.,
commercial drivers, was 49 days, while patients with severe obstructive sleep
apnoea but not 'at risk' waited 261 days for continuous positive airway pressure.
Ten percent of patients required polysomnography, and 4% saw a sleep specialist.
In conclusion, establishment of a community sleep assessment service and sleep
multi-disciplinary meeting led to significantly more assessments, with short
waiting times for treatment, especially in high-risk patients with severe
obstructive sleep apnoea. Most patients can be assessed without more complex
studies or face-to-face review by a sleep specialist. SLEEP DISORDERS: MORE
ASSESSMENTS, SHORTER WAITS WITH COMMUNITY SLEEP SERVICE: A community-based
service for common sleep disorders can provide rapid and easily accessed sleep
assessment and treatment. A team led by Michael Hlavac and Michael Epton from
Christchurch Hospital describe the creation of a sleep assessment service within
the Canterbury district of New Zealand, in which initial assessments are
conducted throughout the community by general practice teams under guidance and
advice from sleep specialists at the region's largest hospital. Before the
service, there were around 300 sleep assessments per year in all of Canterbury, a
region with a population of around 510,000. Now, that number has more than
tripled, with shorter waiting times for treatment, especially for people with
severe sleep apnoea. The authors conclude that most patients can be assessed for
a suspected sleep disorder without needing to visit a hospital's sleep unit.
PMID- 28424460
TI - Generation of heritable germline mutations in the jewel wasp Nasonia vitripennis
using CRISPR/Cas9.
AB - The revolutionary RNA-guided endonuclease CRISPR/Cas9 system has proven to be a
powerful tool for gene editing in a plethora of organisms. Here, utilizing this
system we developed an efficient protocol for the generation of heritable
germline mutations in the parasitoid jewel wasp, Nasonia vitripennis, a rising
insect model organism for the study of evolution, development of axis pattern
formation, venom production, haplo-diploid sex determination, and host-symbiont
interactions. To establish CRISPR-directed gene editing in N. vitripennis, we
targeted a conserved eye pigmentation gene cinnabar, generating several
independent heritable germline mutations in this gene. Briefly, to generate these
mutants, we developed a protocol to efficiently collect N. vitripennis eggs from
a parasitized flesh fly pupa, Sarcophaga bullata, inject these eggs with
Cas9/guide RNA mixtures, and transfer injected eggs back into the host to
continue development. We also describe a flow for screening mutants and
establishing stable mutant strains through genetic crosses. Overall, our results
demonstrate that the CRISPR/Cas9 system is a powerful tool for genome
manipulation in N. vitripennis, with strong potential for expansion to target
critical genes, thus allowing for the investigation of several important
biological phenomena in this organism.
PMID- 28424461
TI - A lack of coordination between sister-chromatids segregation and cytokinesis in
the oocytes of B6.YTIR (XY) sex-reversed female mice.
AB - The B6.YTIR (XY) mouse develops bilateral ovaries despite the expression of the
testis-determining gene Sry during gonadal differentiation. We reported that the
oocytes of the XY female are defective in their cytoplasm, resulting in a failure
in the second meiotic division after activation or fertilization in vitro.
However, the mechanism of meiotic failure or the cause of infertility remained to
be clarified. In the present study, we obtained mature oocytes from XY females by
superovulation and confirmed that these oocytes also fail in zygotic development.
By using confocal microscopy 3D-analysis, we demonstrated that meiotic spindles
were properly positioned and oriented in the MII-oocytes from XY females. After
parthenogenic activation, fewer oocytes from XY females extruded the second polar
body, and in those oocytes, sister-chromatids were often separated but neither
set entered the second polar body. ARP2, F-actin, and ORC4, known to play roles
in asymmetric meiotic division, were initially localized along the ooplasmic
membrane and concentrated over the MII-spindle but lost their cortical polarity
after activation while the sister-chromatids moved away from the oolemma in the
oocytes from XY females. Our results indicate that the second polar body
extrusion is uncoupled from the sister-chromatids separation in the oocytes from
XY female mouse.
PMID- 28424462
TI - Dietary behaviour of man-eating lions as revealed by dental microwear textures.
AB - Lions (Panthera leo) feed on diverse prey species, a range that is broadened by
their cooperative hunting. Although humans are not typical prey, habitual man
eating by lions is well documented. Fathoming the motivations of the Tsavo and
Mfuwe man-eaters (killed in 1898 in Kenya and 1991 in Zambia, respectively) may
be elusive, but we can clarify aspects of their behaviour using dental microwear
texture analysis. Specifically, we analysed the surface textures of lion teeth to
assess whether these notorious man-eating lions scavenged carcasses during their
depredations. Compared to wild-caught lions elsewhere in Africa and other large
feliforms, including cheetahs and hyenas, dental microwear textures of the man
eaters do not suggest extreme durophagy (e.g. bone processing) shortly before
death. Dental injuries to two of the three man-eaters examined may have induced
shifts in feeding onto softer foods. Further, prompt carcass reclamation by
humans likely limited the man-eaters' access to bones. Man-eating was likely a
viable alternative to hunting and/or scavenging ungulates due to dental disease
and/or limited prey availability.
PMID- 28424463
TI - Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free
Bioassays.
AB - Spectral overlaps among the multiple optical readouts commonly cause optical
contamination in fluorescence and bioluminescence. To tackle this issue, we
created five-different lineages of coelenterazine (CTZ) analogues designed to
selectively illuminate a specific luciferase with unique luciferase selectivity.
In the attempt, we found that CTZ analogues with ethynyl or styryl groups display
dramatically biased bioluminescence to specific luciferases and pHs by modifying
the functional groups at the C-2 and C-6 positions of the imidazopyradinone
backbone of CTZ. The optical contamination-free feature was exemplified with the
luciferase-specific CTZ analogues, which illuminated anti-estrogenic and
rapamycin activities in a mixture of optical probes. This unique bioluminescence
platform has great potential for specific and high throughput imaging of multiple
optical readouts in bioassays without optical contamination.
PMID- 28424464
TI - [18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo
imaging in a sodium iodide symporter-expressing tumor model.
AB - Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in
vivo cancer cell tracking in spontaneously metastasizing tumor models still poses
a challenge requiring highest sensitivity and excellent contrast. The goal of
this study was to evaluate if the recently introduced PET radiotracer
[18F]tetrafluoroborate ([18F]BF4-) is useful for sensitive and specific
metastasis detection in an orthotopic xenograft breast cancer model expressing
the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was
complemented by ex vivo fluorescence microscopy and gamma-counting of harvested
tissues. Radionuclide imaging with [18F]BF4- (PET/CT) was compared to the
conventional tracer [123I]iodide (sequential SPECT/CT). We found that [18F]BF4-
was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster
and more complete clearance from circulation. [18F]BF4--PET was also highly
specific as in all detected tissues cancer cell presence was confirmed
microscopically. Undetected comparable tissues were similarly found to be free of
metastasis. Metastasis detection by routine metabolic imaging with [18F]FDG-PET
failed due to low standard uptake values and low contrast caused by adjacent
metabolically active organs in this model. [18F]BF4--PET combined with NIS
expressing disease models is particularly useful whenever preclinical in vivo
cell tracking is of interest.
PMID- 28424465
TI - Predicting the potential distribution in China of Euwallacea fornicates
(Eichhoff) under current and future climate conditions.
AB - Euwallacea fornicatus (Eichhoff) is an important forest pest that has caused
serious damage in America and Vietnam. In 2014, it attacked forests of Acer
trialatum in the Yunnan province of China, creating concern in China's Forestry
Bureau. We used the CLIMEX model to predict and compare the potential
distribution for E. fornicates in China under current (1981-2010) and projected
climate conditions (2011-2040) using one scenario (RCP8.5) and one global climate
model (GCM), CSIRO-Mk3-6-0. Under both current and future climate conditions, the
model predicted E. fornicates to be mainly distributed in the south of China.
Comparing distributions under both climate conditions showed that the area of
potential distribution was projected to increase (mainly because of an increase
in favourable habitat) and shift to the north. Our results help clarify the
potential effect of climate change on the range of this forest pest and provide a
reference and guide to facilitate its control in China.
PMID- 28424466
TI - The role of the brown adipose tissue in beta3-adrenergic receptor activation
induced sleep, metabolic and feeding responses.
AB - Brown adipose tissue (BAT) is regulated by the sympathetic nervous system via
beta3-adrenergic receptors (beta3-AR). Here we tested the hypothesis that
pharmacological stimulation of beta3-ARs leads to increased sleep in mice and if
this change is BAT dependent. In wild-type (WT) animals, administration of CL
316,243, a selective beta3-AR agonist, induced significant increases in non-rapid
eye movement sleep (NREMS) lasting for 4-10 h. Simultaneously,
electroencephalographic slow-wave activity (SWA) was significantly decreased and
body temperature was increased with a delay of 5-6 h. In uncoupling protein 1
(UCP-1) knockout mice, the middle and highest doses of the beta3-AR agonist
increased sleep and suppressed SWA, however, these effects were significantly
attenuated and shorter-lasting as compared to WT animals. To determine if
somnogenic signals arising from BAT in response to beta3-AR stimulation are
mediated by the sensory afferents of BAT, we tested the effects of CL-316,243 in
mice with the chemical deafferentation of the intra-scapular BAT pads. Sleep
responses to CL-316,243 were attenuated by ~50% in intra-BAT capsaicin-treated
mice. Present findings indicate that the activation of BAT via beta3-AR leads to
increased sleep in mice and that this effect is dependent on the presence of UCP
1 protein and sleep responses require the intact sensory innervation of BAT.
PMID- 28424467
TI - The Time Course of Spatial Attention Shifts in Elementary Arithmetic.
AB - It has been proposed that elementary arithmetic induces spatial shifts of
attention. However, the timing of this arithmetic-space association remains
unknown. Here we investigate this issue with a target detection paradigm.
Detecting targets in the right visual field was faster than in the left visual
field when preceded by an addition operation, while detecting targets in the left
visual field was faster than in the right visual field when preceded by a
subtraction operation. The arithmetic-space association was found both at the end
of the arithmetic operation and during calculation. In contrast, the processing
of operators themselves did not induce spatial biases. Our results suggest that
the arithmetic-space association resides in the mental arithmetic operation
rather than in the individual numbers or the operators. Moreover, the temporal
course of this effect was different in addition and subtraction.
PMID- 28424468
TI - Effect of handgrip on coronary artery disease and myocardial infarction: a
Mendelian randomization study.
AB - Observational studies have reported an association of handgrip strength with risk
of cardiovascular disease. However, residual confounding and reverse causation
may have influenced these findings. A Mendelian randomization (MR) study was
conducted to examine whether handgrip is causally associated with cardiovascular
disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were
used as the genetic instruments for handgrip. The effect of each SNP on coronary
artery disease/myocardial infarction (CAD/MI) was weighted by its effect on
handgrip strength, and estimates were pooled to provide a summary measure for the
effect of increased handgrip on risk of CAD/MI. MR analysis showed that higher
grip strength reduces risk for CAD/MI, with 1-kilogram increase in genetically
determined handgrip reduced odds of CAD by 6% (odds ratio (OR) = 0.94, 95%
confidence interval (CI) 0.91-0.99, P = 0.01), and reduced odds of MI by 7% (OR =
0.93, 95% CI 0.89-0.98, P = 0.003). No association of grip strength with type 2
diabetes, body mass index, LDL- and HDL-cholesterol, triglycerides and fasting
glucose was found. The inverse causal relationship between handgrip and the risk
of CAD or MI suggests that promoting physical activity and resistance training to
improve muscle strength may be important for cardiovascular health.
PMID- 28424469
TI - Thermally Triggered Mechanically Destructive Electronics Based On Electrospun
Poly(epsilon-caprolactone) Nanofibrous Polymer Films.
AB - Electronics, which functions for a designed time period and then degrades or
destructs, holds promise in medical implants, reconfigurable electronic devices
and/or temporary functional systems. Here we report a thermally triggered
mechanically destructive device, which is constructed with an ultra-thin
electronic components supported by an electrospun poly(epsilon-caprolactone)
nanofibrous polymer substrate. Upon heated over the melting temperature of the
polymer, the pores of the nanofibers collapse due to the nanofibers' microscopic
polymer chain relaxing and packing. As a result, the polymer substrate exhibits
approximately 97.5% area reduction. Ultra-thin electronic components can
therefore be destructed concurrently. Furthermore, by integrating a thin
resistive heater as the thermal trigger of Joule heating, the device is able to
on-demand destruct. The experiment and analytical results illustrate the
essential aspects and theoretical understanding for the thermally triggered
mechanical destructive devices. The strategy suggests a viable route for
designing destructive electronics.
PMID- 28424470
TI - Atom size electron vortex beams with selectable orbital angular momentum.
AB - The decreasing size of modern functional magnetic materials and devices cause a
steadily increasing demand for high resolution quantitative magnetic
characterization. Transmission electron microscopy (TEM) based measurements of
the electron energy-loss magnetic chiral dichroism (EMCD) may serve as the needed
experimental tool. To this end, we present a reliable and robust electron-optical
setup that generates and controls user-selectable single state electron vortex
beams with defined orbital angular momenta. Our set-up is based on a standard
high-resolution scanning TEM with probe aberration corrector, to which we added a
vortex generating fork aperture and a miniaturized aperture for vortex selection.
We demonstrate that atom size probes can be formed from these electron vortices
and that they can be used for atomic resolution structural and spectroscopic
imaging - both of which are prerequisites for future atomic EMCD investigations.
PMID- 28424471
TI - Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at
the LH and LH/CG Receptors.
AB - Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) have been
considered biologically equivalent because of their structural similarities and
their binding to the same receptor; the LH/CGR. However, accumulating evidence
suggest that LH/CGR differentially responds to the two hormones triggering
differential intracellular signaling and steroidogenesis. The mechanistic basis
of such differential responses remains mostly unknown. Here, we compared the
abilities of recombinant rhLH and rhCG to elicit cAMP, beta-arrestin 2
activation, and steroidogenesis in HEK293 cells and mouse Leydig tumor cells
(mLTC-1). For this, BRET and FRET technologies were used allowing quantitative
analyses of hormone activities in real-time and in living cells. Our data
indicate that rhLH and rhCG differentially promote cell responses mediated by
LH/CGR revealing interesting divergences in their potencies, efficacies and
kinetics: rhCG was more potent than rhLH in both HEK293 and mLTC-1 cells.
Interestingly, partial effects of rhLH were found on beta-arrestin recruitment
and on progesterone production compared to rhCG. Such a link was further
supported by knockdown experiments. These pharmacological differences demonstrate
that rhLH and rhCG act as natural biased agonists. The discovery of novel
mechanisms associated with gonadotropin-specific action may ultimately help
improve and personalize assisted reproduction technologies.
PMID- 28424472
TI - Temperature-dependent folding allows stable dimerization of secretory and virus
associated E proteins of Dengue and Zika viruses in mammalian cells.
AB - Dengue and Zika are two of the most important human viral pathogens worldwide. In
both cases, the envelope glycoprotein E is the main target of the antibody
response. Recently, new complex quaternary epitopes were identified which are the
consequence of the arrangement of the antiparallel E dimers on the viral surface.
Such epitopes can be exploited to develop more efficient cross-neutralizing
vaccines. Here we describe a successful covalent stabilization of E dimers from
Dengue and Zika viruses in mammalian cells. Folding and dimerization of secretory
E was found to be strongly dependent on temperature but independent of PrM co
expression. In addition, we found that, due to the close relationship between
flaviviruses, Dengue and Zika viruses E proteins can form heterodimers and
assemble into mosaic viral particles. Finally, we present new virus-free
analytical platforms to study and screen antibody responses against Dengue and
Zika, which allow for differentiation of epitopes restricted to specific domains,
dimers and higher order arrangements of E.
PMID- 28424473
TI - Highly gate-tuneable Rashba spin-orbit interaction in a gate-all-around InAs
nanowire metal-oxide-semiconductor field-effect transistor.
AB - III-V semiconductors have been intensively studied with the goal of realizing
metal-oxide-semiconductor field-effect transistors (MOSFETs) with high mobility,
a high on-off ratio, and low power consumption as next-generation transistors
designed to replace current Si technology. Of these semiconductors, a narrow band
gap semiconductor InAs has strong Rashba spin-orbit interaction, thus making it
advantageous in terms of both high field-effect transistor (FET) performance and
efficient spin control. Here we report a high-performance InAs nanowire MOSFET
with a gate-all-around (GAA) structure, where we simultaneously control the spin
precession using the Rashba interaction. Our FET has a high on-off ratio
(104~106) and a high field-effect mobility (1200 cm2/Vs) and both values are
comparable to those of previously reported nanowire FETs. Simultaneously, GAA
geometry combined with high- kappa dielectric enables the creation of a large and
uniform coaxial electric field (>107 V/m), thereby achieving highly controllable
Rashba coupling (1 * 10-11 eVm within a gate-voltage swing of 1 V), i.e. an
operation voltage one order of magnitude smaller than those of back-gated
nanowire MOSFETs. Our demonstration of high FET performance and spin
controllability offers a new way of realizing low-power consumption nanoscale
spin MOSFETs.
PMID- 28424474
TI - Molecular epidemiology and azole resistance mechanism study of Candida
guilliermondii from a Chinese surveillance system.
AB - We studied the molecular epidemiology and mechanism of azole resistance of 164 C.
guilliermondii isolates from a nationwide multi-center surveillance program. The
isolates were identified by ITS gene sequencing, and the in vitro susceptibility
to fluconazole and voriconazole was determined by broth microdilution method. The
14-alpha-demethylase gene ERG11 was amplified and sequenced, and microsatellite
analysis was performed to study the genetic relatedness of the isolates. Amongst
the 164 C. guilliermondii isolates, 15 (9.1%) and 17 (10.4%) isolates were
assigned to be non-wild type (non-WT) to fluconazole and voriconazole,
respectively. Sixteen sequence types (STs) were detected by comparing the amino
acid sequence polymorphisms of the ERG11 gene. Fifteen isolates of STs 9, 10, 12,
13, 14, 15 and 16, were all assigned to be non-WT to fluconazole and
voriconazole. By microsatellite analysis, 40 different genotypes were identified.
Thirty-seven isolates from one hospital (Z1) shared the same ERG11 sequence type
(ST 2), microsatellite genotype (PU40) and drug resistance pattern. In
conclusion, this is the first molecular epidemiology study of C. guilliermondii
in China. The rate of non-WT isolates to azoles was high and the accurate
contribution of ERG11 gene mutations to azole resistance need be confirmed by
further studies.
PMID- 28424475
TI - Achieving unlimited recording length in interference lithography via broad-beam
scanning exposure with self-referencing alignment.
AB - Large-area holographic gratings are of great importance in diverse fields
including long-range interference metrology, high-resolution astronomical
telescopes, and chirped-pulse-amplification systems. However, in conventional
interference lithography, the recording length is limited by the aperture of the
collimating lenses. Here we propose broad-beam scanning exposure which employs
the latent grating generated continuously during scanning for real-time dynamic
fringe locking and thus achieves unlimited recording length. This method is
experimentally proved to make high-quality gratings, and is expected to be a new
type of interference lithography.
PMID- 28424477
TI - Warming impact on herbivore population composition affects top-down control by
predators.
AB - Understanding warming impact on herbivores facilitates predicting plant/crop
dynamics in natural/agricultural systems. However, it remains unclear how warming
will affect herbivore population size and population composition, consequently
altering herbivore colonization in a tri-trophic system (plant-herbivore-predator
or crop-pest-biocontrol agent). We studied a soybean-aphid-lady beetle system, by
conducting (1) a laboratory warming experiment to examine warming impact (+2
degrees C or +4 degrees C) on the aphid population size and composition (alate
proportion), and (2) a field colonization experiment to examine whether the
warming-induced effect subsequently interacts with predators (lady beetles) in
affecting aphid colonization. The results showed that warming affected the
initial aphid population composition (reduced alate proportion) but not
population size; this warming-induced effect strengthened the top-down control by
lady beetles and slowing aphid colonization. In other words, biocontrol on crop
pests by predators could improve under 2-4 degrees C warming. Furthermore, aphid
colonization was affected by an interaction between the alate proportion and
predator (lady beetle) presence. This study suggests that warming affects
herbivore population composition and likely mediates top-down control on
herbivore colonization by predators. This mechanism may be crucial but
underappreciated in climate change ecology because population composition (wing
form, sex ratio, age/body size structure) shifts in many species under
environmental change.
PMID- 28424476
TI - Neurons Export Extracellular Vesicles Enriched in Cysteine String Protein and
Misfolded Protein Cargo.
AB - The fidelity of synaptic transmission depends on the integrity of the protein
machinery at the synapse. Unfolded synaptic proteins undergo refolding or
degradation in order to maintain synaptic proteostasis and preserve synaptic
function, and buildup of unfolded/toxic proteins leads to neuronal dysfunction.
Many molecular chaperones contribute to proteostasis, but one in particular,
cysteine string protein (CSPalpha), is critical for proteostasis at the synapse.
In this study we report that exported vesicles from neurons contain CSPalpha.
Extracellular vesicles (EV's) have been implicated in a wide range of functions.
However, the functional significance of neural EV's remains to be established.
Here we demonstrate that co-expression of CSPalpha with the disease-associated
proteins, polyglutamine expanded protein 72Q huntingtinex degrees n1 or
superoxide dismutase-1 (SOD-1G93A) leads to the cellular export of both 72Q
huntingtinex degrees n1 and SOD-1G93A via EV's. In contrast, the inactive
CSPalphaHPD-AAA mutant does not facilitate elimination of misfolded proteins.
Furthermore, CSPalpha-mediated export of 72Q huntingtinex degrees n1 is reduced
by the polyphenol, resveratrol. Our results indicate that by assisting local
lysosome/proteasome processes, CSPalpha-mediated removal of toxic proteins via
EVs plays a central role in synaptic proteostasis and CSPalpha thus represents a
potential therapeutic target for neurodegenerative diseases.
PMID- 28424478
TI - The prevalence of thalassemia in mainland China: evidence from epidemiological
surveys.
AB - Comprehensive data regarding the epidemiology and prevalence of thalassemia in
mainland China are lacking. To assess the prevalence of thalassemia, we performed
a meta-analysis including 16 articles published from 1981 to 2015. The overall
prevalence of alpha-thalassemia, beta-thalassemia and alpha + beta-thalassemia
was 7.88%, 2.21% and 0.48%, respectively. Trends in thalassemia prevalence in
mainland China were not steady; a prevalence map based on a geographic
information system (GIS) showed that the geographic distribution of thalassemia
was highest in the south of China and decreased from south to north.
Additionally, the most common alpha- and beta-globin gene mutation was --SEA and
CD41/42, respectively. The current study provides valuable information regarding
epidemiology and intervention and supports the planning, implementation and
management of prevention programmes for public health.
PMID- 28424479
TI - Wnt-beta Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis
and Dysfunction of the External Anal Sphincter.
AB - Wnt-beta catenin is an important signaling pathway in the genesis of fibrosis in
many organ systems. Our goal was to examine the role of Wnt pathway in the
external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New
Zealand White female rabbits were subjected to surgical EAS myotomy and
administered local injections of either a Wnt antagonist (sFRP-2; daily for 7
days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured
for 15 weeks after which the animals were sacrificed. Anal canal was harvested
and processed for histochemical studies (Masson trichrome stain), molecular
markers of fibrosis (collagen and transforming growth factor-beta) and
immunostaining for beta catenin. Surgical myotomy of the EAS resulted in
significant impairment in anal canal pressure and EAS muscle L-T function.
Following myotomy, the EAS muscle was replaced with fibrous tissue.
Immunostaining revealed beta catenin activation and molecular studies revealed
1.5-2 fold increase in the levels of markers of fibrosis. Local injection of sFRP
2 attenuated the beta catenin activation and fibrosis. EAS muscle content and
function was significantly improved following sFRP-2 treatment. Our studies
suggest that upregulation of Wnt signaling is an important molecular mechanism of
injury related EAS muscle fibrosis and sphincter dysfunction.
PMID- 28424480
TI - Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex
III deficiency caused by a Bcs1l mutation.
AB - Mitochondrial disorders are among the most prevalent inborn errors of metabolism
but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate
ketogenic diets (KDs) have shown beneficial effects in mouse models of
mitochondrial myopathies, with induction of mitochondrial biogenesis as the
suggested main mechanism. We fed KD to mice with respiratory chain complex III
(CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII
assembly factor. The mutant mice became persistently ketotic and tolerated the KD
for up to 11 weeks. Liver disease progression was attenuated by KD as shown by
delayed fibrosis, reduced cell death, inhibition of hepatic progenitor cell
response and stellate cell activation, and normalization of liver enzyme
activities. Despite no clear signs of increased mitochondrial biogenesis in the
liver, CIII assembly and activity were improved and mitochondrial morphology in
hepatocytes normalized. Induction of hepatic glutathione transferase genes and
elevated total glutathione level were normalized by KD. Histological findings and
transcriptome changes indicated modulation of liver macrophage populations by the
mutation and the diet. These results reveal a striking beneficial hepatic
response to KD in mice with mitochondrial hepatopathy and warrant further
investigations of dietary modification in the management of these conditions in
patients.
PMID- 28424481
TI - The first genome-wide association study identifying new susceptibility loci for
obstetric antiphospholipid syndrome.
AB - Antiphospholipid syndrome (APS) is the most important treatable cause of
recurrent pregnancy loss. The live birth rate is limited to only 70-80% in
patients with APS undergoing established anticoagulant therapy. Lupus
anticoagulant (LA), but not anticardiolipin antibody (aCL), was found to predict
adverse pregnancy outcome. Recent genome-wide association studies (GWAS) of APS
focusing on aCL have shown that several molecules may be involved. This is the
first GWAS for obstetric APS focusing on LA. A GWAS was performed to compare 115
Japanese patients with obstetric APS, diagnosed according to criteria of the
International Congress on APS, and 419 healthy individuals. Allele or genotype
frequencies were compared in a total of 426 344 single-nucleotide polymorphisms
(SNPs). Imputation analyses were also performed for the candidate regions
detected by the GWAS. One SNP (rs2288493) located on the 3'-UTR of TSHR showed an
experiment-wide significant APS association (P=7.85E-08, OR=6.18) under a
recessive model after Bonferroni correction considering the number of analyzed
SNPs. Another SNP (rs79154414) located around the C1D showed a genome-wide
significant APS association (P=4.84E-08, OR=6.20) under an allelic model after
applying the SNP imputation. Our findings demonstrate that a specific genotype of
TSHR and C1D genes can be a risk factor for obstetric APS.
PMID- 28424482
TI - Logistic Bayesian LASSO for genetic association analysis of data from complex
sampling designs.
AB - Detecting gene-environment interactions with rare variants is critical in
dissecting the etiology of common diseases. Interactions with rare haplotype
variants (rHTVs) are of particular interest. At the same time, complex sampling
designs, such as stratified random sampling, are becoming increasingly popular
for designing case-control studies, especially for recruiting controls. The US
Kidney Cancer Study (KCS) is an example, wherein all available cases were
included while the controls at each site were randomly selected from the
population by frequency matching with cases based on age, sex and race. There is
currently no rHTV association method that can account for such a complex sampling
design. To fill this gap, we consider logistic Bayesian LASSO (LBL), an existing
rHTV approach for case-control data, and show that its model can easily
accommodate the complex sampling design. We study two extensions that include
stratifying variables either as main effects only or with additional modeling of
their interactions with haplotypes. We conduct extensive simulation studies to
compare the complex sampling methods with the original LBL methods. We find that,
when there is no interaction between haplotype and stratifying variables, both
extensions perform well while the original LBL methods lead to inflated type I
error rates. However, when such an interaction exists, it is necessary to include
the interaction effect in the model to control the type I error rate. Finally, we
analyze the KCS data and find a significant interaction between (current) smoking
and a specific rHTV in the N-acetyltransferase 2 gene.
PMID- 28424483
TI - Magnetic moment of inertia within the torque-torque correlation model.
AB - An essential property of magnetic devices is the relaxation rate in magnetic
switching which strongly depends on the energy dissipation. This is described by
the Landau-Lifshitz-Gilbert equation and the well known damping parameter, which
has been shown to be reproduced from quantum mechanical calculations. Recently
the importance of inertia phenomena have been discussed for magnetisation
dynamics. This magnetic counterpart to the well-known inertia of Newtonian
mechanics, represents a research field that so far has received only limited
attention. We present and elaborate here on a theoretical model for calculating
the magnetic moment of inertia based on the torque-torque correlation model.
Particularly, the method has been applied to bulk itinerant magnets and we show
that numerical values are comparable with recent experimental measurements. The
theoretical analysis shows that even though the moment of inertia and damping are
produced by the spin-orbit coupling, and the expression for them have common
features, they are caused by very different electronic structure mechanisms. We
propose ways to utilise this in order to tune the inertia experimentally, and to
find materials with significant inertia dynamics.
PMID- 28424484
TI - The tandem Agenet domain of fragile X mental retardation protein interacts with
FUS.
AB - The tandem Agenet domain (TAD) of fragile X mental retardation protein (FMRP)
protein is considered to be a member of the methyl-lysine-binding Tudor domain
"Royal family". Several groups have reported that the TAD binds with methylated
histones and plays a role in DNA damage responses. FMRP is a RNA-binding protein
predominantly resident in cytoplasm. Therefore, in this study, we identified
DDX5, FUS, EWSR1 and LSM14A as TAD-interacting proteins sensitive to F32L and/or
Y96L mutation by pull-down assays and mass spectrometry. We also showed that the
interaction is potentially mediated by RGG/RG motifs. Furthermore, when FMRP was
knocked-down, translocation of exogenously expressed wild-type FUS and disease
related mutant R514G was observed. This study may provide a novel insight into
FMRP involvement in the intracellular localization of FUS and pathology of FUS
related amyotrophic lateral sclerosis.
PMID- 28424485
TI - In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the
trigeminal ganglia.
AB - The ability to genetically manipulate trigeminal ganglion (TG) neurons would be
useful in the study of the craniofacial nervous system and latent
alphaherpesvirus infections. We investigated adeno-associated virus (AAV) vectors
for gene delivery to the TG after intradermal whiskerpad delivery in mice. We
demonstrated that AAV vectors of serotypes 1, 7, 8, and 9 trafficked from the
whiskerpad into TG neurons and expressed transgenes within cell bodies and axons
of sensory neurons in all three branches of the TG. Gene expression was highest
with AAV1, and steadily increased over time up to day 28. Both constitutive and
neuronal-specific promoters were able to drive transgene expression in TG
neurons. Levels of vector genomes in the TG increased with input dose, and
multiple transgenes could be co-delivered to TG neurons by separate AAV vectors.
In conclusion, AAV1 vectors are suitable for gene delivery to TG sensory neurons
following intradermal whiskerpad injection.
PMID- 28424486
TI - Meta-analysis Reveals the Prognostic Value of Circulating Tumour Cells Detected
in the Peripheral Blood in Patients with Non-Metastatic Colorectal Cancer.
AB - Detecting circulating tumour cells (CTCs) is considered as effective and
minimally invasive technique to predict the prognosis of patients with metastatic
colorectal cancer (CRC), but its clinical validity is still conflicting in
patients without metastasis. We performed this meta-analysis to evaluate whether
detection of CTCs in the peripheral blood can be used as a prognostic marker for
patients with non-metastatic CRC. We performed a comprehensive search of the
EMBASE, PubMed, and Web of Science databases (up to September 2016). Meta
analyses were conducted using a random-effects model with the hazard ratio (HR)
and 95% confidence interval (95% CI) as the effect measures. Twenty studies
including 3,687 patients were eligible for inclusion. Overall analyses
demonstrated that the presence of CTCs was significantly associated with
aggressive disease progression (HR = 2.57, 95% CI = 1.64-4.02, P heterogeneity <
0.001, I 2 = 81.0%) and reduced disease survival (HR = 2.41, 95% CI = 1.66-3.51,
P heterogeneity = 0.002, I 2 = 59.7%). Subgroup analyses further supported the
prognostic effect of CTCs based on different subsets, including sampling time,
detection method and cancer type. Our findings suggest that detection of CTCs in
the peripheral blood has the clinical utility to indicate poor prognosis in
patients with non-metastatic CRC.
PMID- 28424487
TI - Power Flow in a Large-Core Multimode Fiber under External Perturbation and its
Applications.
AB - Large core optical multimode fiber provides benefits such as a large light
coupling tolerance, easy handling, and delivery of higher light power without
undesirable nonlinear effects. In this research, we exploit the effects of
external perturbation on the power flow within the large core fiber and present
two relevant applications, namely a perturbation sensor and a doughnut beam
tuner. Since conventional multimode fiber power flow model does not take into
consideration the perturbation effect, we modify the power flow model so that the
influence of time varying perturbation can be theoretically analyzed. Based on
our theory, we further conduct the numerical simulation and experiments on these
two applications. For the fiber vibration sensor, the proposed numerical model
shows that the sensor sensitivity depends on the intensity profile of the
launched beam and also the higher-order harmonics that were not reported
previously can become interferences to affect the signal. For the beam tuner
application, we prove both theoretically and experimentally that the doughnut
intensity profile at the fiber output can be tuned in real-time by applying
external perturbations to the fiber. We expect that the results can be useful to
further exploit the external perturbation on large core fiber in various
applications.
PMID- 28424488
TI - Improving superconductivity in BaFe2As2-based crystals by cobalt clustering and
electronic uniformity.
AB - Quantum materials such as antiferromagnets or superconductors are complex in that
chemical, electronic, and spin phenomena at atomic scales can manifest in their
collective properties. Although there are some clues for designing such
materials, they remain mainly unpredictable. In this work, we find that
enhancement of transition temperatures in BaFe2As2-based crystals are caused by
removing local-lattice strain and electronic-structure disorder by thermal
annealing. While annealing improves Neel-ordering temperature in BaFe2As2 crystal
(T N = 132 K to 136 K) by improving in-plane electronic defects and reducing
overall a-lattice parameter, it increases superconducting-ordering temperature in
optimally cobalt-doped BaFe2As2 crystal (T c = 23 to 25 K) by precipitating-out
the cobalt dopants and giving larger overall a-lattice parameter. While annealing
improves local chemical and electronic uniformity resulting in higher T N in the
parent, it promotes nanoscale phase separation in the superconductor resulting in
lower disparity and strong superconducting band gaps in the dominant crystal
regions, which lead to both higher overall T c and critical-current-density, J c
.
PMID- 28424489
TI - Porous Graphene Sponge Additives for Lithium Ion Batteries with Excellent Rate
Capability.
AB - Rate capability as well as power performance of lithium ion batteries (LiBs) is
becoming more and more important, especially as the application targets of LiBs
move from mobile devices to transportation, such as EVs and HEVs. In this
research, we report porous graphene sponge additives for both anode and cathode
materials for better rate performance. The charge capacity retention improved
from 56% to 77% at 6C and from 7% to 45% at 10C with 0.5 wt% added to the anode,
while the discharge capacity retention at the 6C rate improved from 43% to 76%
and the 10C rate discharge improved from 16% to 40% with the same amount of MG
added to the cathode. The cyclability at high rate was also improved with the MG
additive. Moreover, preparation of the MG was facile, cost-effective, and
compatible with commercially available active materials. These results
demonstrate the suitability of MG for use with LiB additives to ensure better
rate capability and high rate cyclability.
PMID- 28424490
TI - Direct recognition of LPS drive TLR4 expressing CD8+ T cell activation in
patients with rheumatoid arthritis.
AB - Aberrant immune responses characterize autoimmune disorders like Rheumatoid
Arthritis (RA) wherein lymphocytes are recognized as key players. Role of CD8+ T
cells in RA has been less defined however we found that these cells are activated
in RA patients with increased expression of cytolytic granules and inflammatory
mediators thereby modulating immune responses contributing to disease severity.
Though unconventional expression of different Toll Like Receptors (TLRs) on CD8+
T cells has been proposed but their expression and role in T cell activation and
differentiation in RA still remains obscure. Herein we report, for the first
time, an increased expression of TLR4 on peripheral CD8+ T cells of RA patients
and its role in skewing CD8+ T cells towards activated and inflammatory phenotype
thereby playing a significant role in pathogenesis and progression of RA. We
found that the surface expression of TLR4 on CD8+ T cells directly correlates
with disease severity. Moreover, these CD8+ T cells respond to the TLR4 ligand
LPS and express robust amounts of cytotolytic and inflammatory molecules
including TNFalpha and IFNgamma. Our study hence identifies an important role for
CD8+ T cells in orchestrating RA through TLR4 mediated activation and
differentiation.
PMID- 28424491
TI - Understanding the ion-induced elongation of silver nanoparticles embedded in
silica.
AB - In this work we have studied the elongation of silver nanoparticles irradiated
with 40 MeV Bromine ions by means of in situ optical measurements, transmission
electron microscopy and molecular dynamics simulations. The localized surface
plasmon resonance of silver nanoparticles has a strong dependence on the particle
shape and size, which allowed us to obtain the geometrical parameters with
remarkable accuracy by means of a fit of the optical spectra. Optical results
have been compared with transmission electron microscopy images and molecular
dynamics simulations and the agreement is excellent in both cases. An important
advantage of in situ measurements is that they yield an extremely detailed
information of the full elongation kinetics. Final nanoparticle elongation
depends on a complex competition between single-ion deformation, Ostwald ripening
and dissolution. Building and validating theoretical models with the data
reported in this work should be easier than with the information previously
available, due to the unprecedented level of kinetic details obtained from the in
situ measurements.
PMID- 28424492
TI - TestSTORM: Versatile simulator software for multimodal super-resolution
localization fluorescence microscopy.
AB - Optimization of sample, imaging and data processing parameters is an essential
task in localization based super-resolution microscopy, where the final image
quality strongly depends on the imaging of single isolated fluorescent molecules.
A computational solution that uses a simulator software for the generation of
test data stacks was proposed, developed and tested. The implemented advanced
physical models such as scalar and vector based point spread functions,
polarization sensitive detection, drift, spectral crosstalk, structured
background etc., made the simulation results more realistic and helped us
interpret the final super-resolved images and distinguish between real structures
and imaging artefacts.
PMID- 28424493
TI - Regulation of intraocular pressure by microRNA cluster miR-143/145.
AB - Glaucoma is a major cause of irreversible blindness worldwide. Elevated
intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion
cell death, is the primary risk factor for blindness in glaucoma patients. IOP is
controlled by the balance between aqueous humor secretion from the ciliary body
(CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs)
regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143
and miR-145 expression is enriched in the smooth muscle and trabecular meshwork
in the eye. Targeted deletion of miR-143/145 in mice results in significantly
reduced IOP, consistent with an ~2-fold increase in outflow facilities. However,
aqueous humor production in the same mice appears to be normal based on a
microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145
regulates actin dynamics and the contractility of TM cells, consistent with its
regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well
as myosin light chain kinase (MLCK) in these cells. Our data establish miR
143/145 as important regulators of IOP, which may have important therapeutic
implications in glaucoma.
PMID- 28424494
TI - Predictable phenotypic, but not karyotypic, evolution of populations with
contrasting initial history.
AB - The relative impact of selection, chance and history will determine the
predictability of evolution. There is a lack of empirical research on this
subject, particularly in sexual organisms. Here we use experimental evolution to
test the predictability of evolution. We analyse the real-time evolution of
Drosophila subobscura populations derived from contrasting European latitudes
placed in a novel laboratory environment. Each natural population was sampled
twice within a three-year interval. We study evolutionary responses at both
phenotypic (life-history, morphological and physiological traits) and karyotypic
levels for around 30 generations of laboratory culture. Our results show (1)
repeatable historical effects between years in the initial state, at both
phenotypic and karyotypic levels; (2) predictable phenotypic evolution with
general convergence except for body size; and (3) unpredictable karyotypic
evolution. We conclude that the predictability of evolution is contingent on the
trait and level of organization, highlighting the importance of studying multiple
biological levels with respect to evolutionary patterns.
PMID- 28424495
TI - Significance of genetic polymorphisms in long non-coding RNA AC079767.4 in
tuberculosis susceptibility and clinical phenotype in Western Chinese Han
population.
AB - Recent studies have implicated long non-coding RNA, AC079767.4, as a highly
susceptible gene in tuberculosis. The aim of the study was to preliminarily
explore the possible association of single nucleotide polymorphisms (SNPs) in
AC079767.4 gene with clinical phenotypes and TB susceptibility in Western Chinese
Han population. The improved multiplex ligation detection reaction (iMLDR) method
was employed to genotype 4 SNPs in AC079767.4 in 554 tuberculosis patients and
561 healthy individuals. In subgroup analysis, only the C allele for rs12477677
was associated with the decreased susceptibility to pulmonary TB with a p-value
of 0.026, but p-value was 0.103 after Bonferroni correction. In total samples,
haplotype [ACAC], representing four AC079767.4 variants, was found to slightly
decrease TB risk (p = 0.045). Furthermore, patients with the CC genotype of
rs12477677 were correlated with fewer occurrences of fever (p = 0.016), while
patients carrying the T allele were associated with lower levels of ESR in the
dominant model of rs1055229 (p = 0.021). For the first time, we reported the
potential susceptibility and clinical traits of tuberculosis with lncRNA variants
in the Western Han Chinese population. Our data indicate AC079767.4 polymorphisms
may potentially act as novel biomarkers for tuberculosis diagnostic and
therapeutic purposes.
PMID- 28424496
TI - The Chemical Characterization of Nigerian Propolis samples and Their Activity
Against Trypanosoma brucei.
AB - Profiling of extracts from twelve propolis samples collected from eight regions
in Nigeria was carried out using high performance liquid chromatography (LC)
coupled with evaporative light scattering (ELSD), ultraviolet detection (UV) and
mass spectrometry (MS), gas chromatography mass spectrometry (GC-MS) and nuclear
magnetic resonance spectroscopy (NMR). Principal component analysis (PCA) of the
processed LC-MS data demonstrated the varying chemical composition of the
samples. Most of the samples were active against Trypanosoma b. brucei with the
highest activity being in the samples from Southern Nigeria. The more active
samples were fractionated in order to isolate the component(s) responsible for
their activity using medium pressure liquid chromatography (MPLC). Three
xanthones, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, 1,3,7-trihydroxy
4,8-di-(3-methylbut-2-enyl)xanthone a previously undescribed xanthone and three
triterpenes: ambonic acid, mangiferonic acid and a mixture of alpha-amyrin with
mangiferonic acid (1:3) were isolated and characterised by NMR and LC-MS. These
compounds all displayed strong inhibitory activity against T.b. brucei but none
of them had higher activity than the crude extracts. Partial least squares (PLS)
modelling of the anti-trypanosomal activity of the sample extracts using the LC
MS data indicated that high activity in the extracts, as judged from LCMS2 data,
could be correlated to denticulatain isomers in the extracts.
PMID- 28424497
TI - The glycogen synthase kinase MoGsk1, regulated by Mps1 MAP kinase, is required
for fungal development and pathogenicity in Magnaporthe oryzae.
AB - Magnaporthe oryzae, the causal agent of blast disease, is one of the most
destructive plant pathogens, causing significant yield losses on staple crops
such as rice and wheat. The fungus infects plants with a specialized cell called
an appressorium, whose development is tightly regulated by MAPK signaling
pathways following the activation of upstream sensors in response to
environmental stimuli. Here, we show the expression of the Glycogen synthase
kinase 3 (GSK3) MoGSK1 in M. oryzae is regulated by Mps1 MAP kinase, particularly
under the stressed conditions. Thus, MoGSK1 is functionally characterized in this
study. MoGsk1 is functionally homologues to the Saccharomyces cerevisiae GSK3
homolog MCK1. Gene replacement of MoGSK1 caused significant delay in mycelial
growth, complete loss of conidiation and inability to penetrate the host surface
by mycelia-formed appressorium-like structures, consequently resulting in loss of
pathogenicity. However, the developmental and pathogenic defects of Deltamogsk1
are recovered via the heterologous expression of Fusarium graminearum GSK3
homolog gene FGK3, whose coding products also shows the similar cytoplasmic
localization as MoGsk1 does in M. oryzae. By contrast, overexpression of MoGSK1
produced deformed appressoria in M. oryzae. In summary, our results suggest that
MoGsk1, as a highly conservative signal modulator, dictates growth, conidiation
and pathogenicity of M. oryzae.
PMID- 28424498
TI - Efficacy and safety of a newly developed polylactic acid microsphere as an
injectable bulking agent for penile augmentation: 18-months follow-up.
AB - Polylactic acid (PLA) fillers are widely used for cosmetic volume augmentation.
But, no study has evaluated the use of PLA filler in penile augmentation (PA No.
4). We evaluated the efficacy and safety of a newly developed PLA filler for PA
during a 18-month follow-up period. A total of 23 healthy adult men were
prospectively enrolled between June and November 2012. Penile girth was measured
at proximal-, mid- and distal-shaft at baseline, 3, 6, 12 and 18 months following
injection. Subjects' satisfaction was assessed with visual analogue scale (VAS).
Adverse events (AEs) were also reported. Mean injected volume was 20 ml. The
circumference of proximal-, mid-, and distal-shaft increased by a mean of 2.2+/
0.2, 2.7+/-1.0 and 2.7+/-1.0 cm at 3 months, respectively (each P<0.001). No
significant differences were noted in girth circumference between 3 and 18 months
post-injection (each P>0.05). VAS score increased from 51.6+/-14.7 at baseline to
64.8+/-19.3 and 74.3+/-14.6 at 3 and 6 months, respectively (each P<0.05). Six
cases of mild, transient treatment-emergent AEs were reported in 5 subjects.
Serious AEs were not reported. In conclusion, penile injection of a newly
developed PLA filler led to significant penile augmentative effects for up to 18
months and was well tolerated without serious AEs.
PMID- 28424499
TI - Tamsulosin for treatment of lower urinary tract symptoms in women: a systematic
review and meta-analysis.
AB - Tamsulosin has been used for the off-label treatment of lower urinary tract
symptoms (LUTS) in women. Over the past few years, several randomized controlled
trials (RCTs) have reported the clinical effectiveness and safety of tamsulosin
for LUTS in women. Therefore, the aim of the present study was to perform a meta
analysis to evaluate the safety and efficacy of tamsulosin in treating LUTS in
women, which may resolve some of the current controversies over use of the drug
and provide more reliable evidence for the use of tamsulosin. A literature review
was performed to identify all published RCTs of tamsulosin for the treatment of
LUTS in women. The search included the following databases: PUBMED, EMBASE, the
Cochrane Controlled Trail Register of Controlled Trials, Chinese Biomedical
Literature Database, China National Knowledge Infrastructure, Chinese Science and
Technique Journals Database (VIP) and Wanfang Database. A systematic review and
meta-analysis were conducted. Six RCTs studies involving 764 female participants
were included in the analysis. Four out of the six RCTs compared tamsulosin with
placebo, one RCT compared tamsulosin with prazosin and the other study compared
tamsulosin with tamsulosin combined with tolterodine. Two RCTs evaluated total
International Prostate Symptom Score (IPSS) and improved total IPSS compared with
the placebo (standardized mean difference=-4.08, 95% confidence interval=-5.93 to
-2.23, P<0.00001). IPSS (storage symptom score), IPSS (voiding symptom score) and
quality-of-life score also showed the similar effects. In addition, tamsulosin
improved the Overactive Bladder Questionnaire score when compared with placebo in
only one RCT. For urodynamic parameters, tamsulosin improved the average flow
rate and the post-void residual volume when compared with prazosin and
tolterodine combined with tamsulosin, respectively. Beyond that, the other
parameters showed no significant difference between the treatment and control
groups. On the basis of the present evidence, tamsulosin is an effective
treatment for the relief of LUTS in women when compared with placebo. However,
the safety of the tamsulosin remains unknown. Further, well-conducted trials that
examine long-term outcomes are required.
PMID- 28424500
TI - Percutaneous transluminal coronary angioplasty for acute myocardial infarction:
the impact on sexual function in men.
AB - The aim of this study was to evaluate changes in men's sexual function after
percutaneous transluminal coronary angioplasty (PTCA) treatment for acute
myocardial infarction (MI). Sixty men aged 18-70 years old were included in the
study. All patients had acute MI and underwent PTCA. They underwent two post PCTA
visits: 3 days and between 4 and 6 months after PTCA. During the first and second
visit a standard medical interview was carried out and sexual function data
collected using Changes in Sexual Functioning Questionnaire and International
Index of Erectile Function (IIEF-15). The results showed no statistical
differences in IIEF and CSQF scores before and after PTCA. However, when cutoff
points were used, a significant decrease in severe erectile dysfunction (ED)
prevalence according to IIEF (25.0% vs 16.7%; P=0.02) was observed. Based on the
results, we concluded that sexual function significantly improved in the subset
of men with severe ED who underwent PTCA as a treatment for acute MI, 4-6 months
after the procedure.
PMID- 28424501
TI - Translation and validation of the Greek version of the female sexual function
index questionnaire.
AB - The clinical evaluation of female sexual dysfunctions should be supplemented by
validated questionnaires; however, there is no specific instrument available in
Greek language. The study was designed to linguistically validate the Greek
version of Female Sexual Function Index (FSFI). Ninety-nine healthy women and
eighteen women with a sexual dysfunction were recruited through a survey and were
asked to voluntarily complete the FSFI questionnaire in Greek (FSFI-Gr) at
baseline and after 2 weeks. We assessed validity, internal consistency
reliability and test-retest reliability of the FSFI greek version. Subscales of
the FSFI showed good internal consistency reliability (Cronbach's=0.92, P<0.01).
Test-retest reliability median 14 days apart was excellent with intraclass
coefficient 0.91 (P<0.01). The FSFI-Gr discriminated between women with and
without sexual dysfunction with an optimal cutoff score 26 (sensitivity 71.4%,
specificity 92.2%). The Greek version of the FSFI is a reliable tool for the
assessment of female sexual dysfunction. The results show that it is comparable
to the outcome of studies in English-speaking countries.
PMID- 28424502
TI - Significance of serum endothelial cell specific molecule-1 (Endocan) level in
patients with erectile dysfunction: a pilot study.
AB - This study aimed to measure the serum endocan level of patients with erectile
dysfunction (ED) and to investigate the possible association between the
Endothelial-specific molecule-1 (Endocan) level and ED. Twenty healthy and sixty
four male patients included in the study were divided into four groups: severe ED
(19 patients), moderate ED (24 patients), mild ED (21 patients) and control group
(20 healthy men). The erectile function of all the patients was evaluated using
the International Index of Erectile Function-5 (IIEF-5) questionnaire. The body
mass index (BMI) of each participant was determined, together with levels of
fasting blood glucose, total testosterone, low- and high-density lipoprotein
cholesterol, triglyceride and endocan in serum samples. No significant difference
was found between the three ED groups and the control group in terms of the mean
age, BMI and the levels of cholesterol and fasting blood glucose (P>0.05). The
mean serum endocan level was found to 1.076+/-0.5, 0.674+/-0.40 and 0.671+/-0.3
ng ml-1 in the severe, moderate and mild ED groups, respectively. This indicated
that the highest value was obtained from the severe ED group, and the difference
between the severe ED group and the other groups was statistically significant.
In the control group, the serum endocan level was 0.73+/-0.46 ng ml-1, which was
significantly higher compared to the moderate and mild ED groups (P<0.05). The
significant difference between the control and ED groups in terms of the serum
endocan level can assist in the evaluation of endothelial pathologies in the
etiology ED.
PMID- 28424503
TI - Sexuality education in Japanese medical schools.
AB - The present study aimed to investigate current sexuality education in Japanese
medical schools and the impact of position title in the Japanese Society for
Sexual Medicine (JSSM). Questionnaires were mailed to urology departments in all
Japanese medical schools. The responses were evaluated according to four factors:
the number of lecture components, curriculum hours, degree of satisfaction with
the components and degree of satisfaction with the curriculum hours. We also
investigated differences in these four factors among three groups: Directors,
Council members and non-members of the JSSM. The medians of curriculum hours and
the number of the lecture components were 90.0 min and 7.0, respectively. The
curriculum hours of the Directors (140.0 min) were significantly longer than
those of the non-members (90.0 min; P<0.05). The number of lecture components
taught by Directors (9.5) was significantly higher than that of the Council (4.0;
P<0.01) and non-members (7.0; P<0.05). More than half of the faculties were not
satisfied with the lecture components and curriculum hours. This is the first
study on sexuality education in Japanese medical schools. It showed the
inadequacy of both curriculum hours and lecture components, and that the position
title of department chair affects sexuality education in medical schools.
PMID- 28424504
TI - Prevalence and factors associated with erectile dysfunction in patients with
chronic kidney disease on conservative treatment.
AB - Population with chronic kidney disease (CKD) has had many problems, and some of
these have arisen from sexual disorders. The present study intends to determine
the prevalence and the associated factors with erectile dysfunction (ED) among
patients with CKD on conservative treatment (CKDCT). This transversal study was
conducted from May 2013 to December 2015. The tools used were: medical records
and the International Index of Erectile Function. Data were analyzed by
univariate and multivariate logistic regression analysis. Among 245 patients that
have participated of this study, ED was present in 71.02% and it was severe in
36.73%. Age greater than 50 years, body mass index lower than 25, diabetes
mellitus, stages IV/V of CKD, cardiac conduction disturbances, benign prostatic
hyperplasia, smoking, alcohol use, albumin <3.5 g per 100 ml and creatinine
clearance between 15 and 29 ml min-1 per 1.73 m2 were associated with ED. Time
of CKD was the only variable associated with ED independent of the presence of
other factors. ED prevalence in patients with CKDCT is high and it is severe in
more than half of them. Several factors are associated with ED in this population
but the principal one is the time of CKD.
PMID- 28424505
TI - Usefulness of serum fetuin-A level as a marker of erectile dysfunction.
AB - This study aimed to evaluate the correlation between serum levels of fetuin-A and
the presence and severity of erectile dysfunction (ED) in Egyptian population.
The study was performed on 60 ED patients and 20 age-matched healthy controls. A
comprehensive medical history and complete physical examination were obtained and
performed in all participants. ED and its severity were assessed via
International Index of Erectile Function (IIEF-5). Doppler ultrasound, fasting
blood glucose level, complete lipid profile, serum total testosterone (TT) and
serum fetuin-A were performed. Our results revealed that there were no
statistically significant differences between the ED group and the controls
regarding body mass index, fetal bovine serum, cholesterol, low-density
lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG). However,
IIEF-5 and serum TT levels were significantly lower in ED patients than controls.
Regarding serum fetuin-A, our data demonstrated that ED patients had
significantly lower serum fetuin-A levels than controls. In addition, patients
with severe ED had lower fetuin-A levels than moderate and mild ED (P<0.001).
Serum fetuin-A levels are positively correlated with cholesterol, LDL, TG and
IIEF-5 and negatively correlated with HDL. In conclusion, serum fetuin-A level
could be a potentially useful and sensitive biomarker for ED diagnosis.
PMID- 28424506
TI - Long-term outcomes of AMS Spectra(r) penile prosthesis implantation and
satisfaction rates.
AB - The aim of this study was to evaluate the surgical implantation techniques of AMS
Spectra malleable penile prosthesis, its intraoperative and postoperative
complications, and the rates of patient and partner satisfaction. Forty-six
patients on whom AMS Spectra malleable penile prosthesis implantation was
performed between 2009 and 2014 were retrospectively examined. Any complications
seen intraoperatively and postoperatively were determined. International Index of
Erectile Function (IIEF)-5, total IIEF erectile function domain scores were
calculated preoperatively. IIEF-5, total IIEF erectile function domain and
Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were
calculated in the postoperative third, sixth and twelfth months. The mean age of
the patients was 63.6+/-7.28 (38-80) years. The mean erectile dysfunction period
was 4.29+/-2.51 years, and the mean follow-up period was 3.19+/-1.6 years. The
mean IIEF-5 score was 5.86+/-0.92 before surgery, and it was 22.5+/-0.62 at the
end of the follow-up. The mean total IIEF erectile function domain score was
6.02+/-1.09 before surgery, and it was 26.02+/-0.21 at the end of the follow-up.
The mean EDITS score was 71.06+/-3.16 at the end of the follow-up. The mean EDITS
score of the patients partners was 65.08+/-4.34 at the end of the follow-up. The
overall satisfaction rates were 96.2% for the patients and 84.6% for the
partners. As a result of this study, the AMS Spectra penile prosthesis
implantation is an effective, reliable and economic method. It can be used in the
treatment of erectile dysfunction in selected patient groups offering high
patient and partner satisfaction rates.
PMID- 28424507
TI - Heat Stress in Dairy Cattle Alters Lipid Composition of Milk.
AB - Heat stress, potentially affecting both the health of animals and the yield and
composition of milk, occurs frequently in tropical, sub-tropical and temperate
regions. A simulated acute heat stress experiment was conducted in controlled
climate chambers and milk samples collected before, during and after the heat
challenge. Milk lipid composition, surveyed using LC-MS, showed significant
changes in triacylglycerol (TAG) and polar lipid profiles. Heat stress
(temperature-humidity index up to 84) was associated with a reduction in TAG
groups containing short- and medium-chain fatty acids and a concomitant increase
in those containing long-chain fatty acids. The abundance of five polar lipid
classes including phosphatidylethanolamine, phosphatidylserine,
phosphatidylcholine, lysophosphatidylcholine and glucosylceramide, was found to
be significantly reduced during heat stress. Lysophosphatidylcholine, showing the
greatest reduction in concentration, also displayed a differential response
between heat tolerant and heat susceptible cows during heat stress. This
phospholipid could be used as a heat stress biomarker for dairy cattle. Changes
in TAG profile caused by heat stress are expected to modify the physical
properties of milk fat, whereas the reduction of phospholipids may affect the
nutritional value of milk. The results are discussed in relation to animal
metabolism adaptation in the event of acute heat stress.
PMID- 28424508
TI - Temperature warming strengthens the mutualism between ghost ants and invasive
mealybugs.
AB - Although the exogenous forces that directly affect the mutualisms between ants
and honeydew-producing hemipterans have been well documented, few studies have
been focused on the impacts of environmental warming on ant-hemipteran
interactions. Here, we investigated how temperature warming affects the mutualism
between ghost ant Tapinoma melanocephalum and invasive mealybug Phenacoccus
solenopsis by experimental manipulation of temperature. We found that higher
temperatures have significant direct effects on the growth rate of mealybug
colony, and the positive effect of ant tending on mealybug colony growth is
temperature-dependent. Honeydew excretion by mealybugs was affected by ant
tending and temperature warming, and was significantly increased under higher
temperature. The effect of ant tending on percentage parasitism was also
influenced by temperature warming. Ant performance including tending level,
aggression, activity, and honeydew consumption was enhanced by temperature
warming, which may provide superior protection to the mealybugs. Our results show
that ghost ant-mealybug mutualism is strengthened in a warmer environment. These
findings may facilitate the prediction of how each partner in the ant-hemipteran
enemy interactions responds to increasing temperature.
PMID- 28424509
TI - Evolution of crystal structures in GeTe during phase transition.
AB - We investigated changes in the crystal structure of GeTe during its phase
transition. Using density functional theory (DFT) calculations, four possible
crystal structures were identified: R3m, P1, Cm, and Fm3m. Among these, P1 and Cm
were examined here for the first time. By calculating the internal energy of the
crystal volume change, we verified that P1, R3m, and Cm can coexist in
crystalline GeTe. The X-ray diffraction spectra of annealed and laser-irradiated
GeTe films revealed coexisting P1 or R3m and Cm. In addition, we confirmed that
Cm transforms into P1 or R3m after laser irradiation. The presence of these new
structures was revealed in the crystal Raman spectra. Many of the Raman peaks in
the crystalized GeTe could be explained by the coexistence of various structures.
By calculating the band gaps of these structures, we also found that a structural
transformation induces a change in the crystal resistance, owing to differences
in the band gaps of individual structures. The generation of new crystal
structures suggests a facile phase change and instability during the structural
transformation.
PMID- 28424510
TI - The effect of slow-loaded breathing training on the blood pressure response to
handgrip exercise in patients with isolated systolic hypertension.
AB - Isolated systolic hypertension (ISH) is the most common form of hypertension in
older people. It is characterized by increased resting systolic blood pressure
(sBP) and increased sBP in response to exercise. It has previously been shown
that slow breathing training reduces resting sBP, and the objective of the
present study was to determine whether it also reduced the blood pressure
response to static handgrip exercise. ISH patients aged between 60 and 74 years
were randomly divided into a control group (10 subjects, 4 of which were male)
that breathed normally and a trained group (10 subjects, 4 of which were male)
that trained daily for 8 weeks by slow breathing against an inspiratory
resistance of 18 cmH2O. Before and immediately after training, subjects underwent
a 2-min handgrip test (30% max) followed by 2 min of post-exercise circulatory
occlusion (PECO) to assess metaboreflex activity. Training reduced sBP by 10.6 mm
Hg (95% confidence interval (CI), -16 to -5 mm Hg, P=0.004), but changes were not
observed in the control group. The peak exercise sBP was reduced by 23 mm Hg (95%
CI, -16 to -31 mm Hg, P<0.001), while the increase in the sBP above resting was
reduced by 12.6 mm Hg (95% CI, -6.9 to -18.2 mm Hg, P=0.002). The sBP during PECO
was reduced by 8.9 mm Hg (95% CI, -4 to -14 mm Hg, P=0.008), which is indicative
of reduced metaboreflex activity; no such change was observed in the control
group. The results demonstrate that conventional treatment of older patients with
ISH may be improved in two ways by slow breathing training: resting sBP may be
reduced by 10 mm Hg, more than can be achieved by conventional pharmacological
therapies, while the response to static exercise may be reduced by approximately
twice this value.
PMID- 28424511
TI - Response of peanut Arachis hypogaea roots to the presence of beneficial and
pathogenic fungi by transcriptome analysis.
AB - Entomopathogenic fungus Metarhizium anisopliae obtain survival benefit meanwhile
promote the nutrient absorption of root as an endophyte. However, little is known
concerning molecular mechanisms in the process. We performed the transcriptome
sequencing of A. hypogaea roots inoculated M. anisopliae and pathogenic Fusarium
axysporum, respectively. There were 81323 unigenes from 132023 transcripts. Total
203 differentially expressed genes (DEGs) respond to the two fungi, including
specific 76 and 34 DEGs distributed respectively in M. anisopliae and F.
axysporum treatment. KEGG pathway enrichment for DEGs showed the two top2 were
signal transductions of plant-pathogen interaction and plant hormone. By qRT-PCR,
the mRNA level of 26 genes involved in plant-fungus interaction confirmed the
reliability of the RNA-Seq data. The expression pattern of the key DEGs on
jasmonic acid (JA) or salicylic acid (SA) signaling pathway presented regulating
consistency with JA or SA concentration detected by HPLC-MS. Those significantly
stronger down-regulated DEGs by M. anisopliae thanby F. axysporum linking to
hypersensitive response and negative regulation of defense, and those specific up
regulated genes in M. anisopliae treatment may predict that the less immunity is
conducive to symbiosis F. axysporum may trigger JA-mediated defense regulated by
ERF branch of JA signaling pathway, whereas M. anisopliae does not.
PMID- 28424512
TI - Human umbilical cord plasma proteins revitalize hippocampal function in aged
mice.
AB - Ageing drives changes in neuronal and cognitive function, the decline of which is
a major feature of many neurological disorders. The hippocampus, a brain region
subserving roles of spatial and episodic memory and learning, is sensitive to the
detrimental effects of ageing at morphological and molecular levels. With
advancing age, synapses in various hippocampal subfields exhibit impaired long
term potentiation, an electrophysiological correlate of learning and memory. At
the molecular level, immediate early genes are among the synaptic plasticity
genes that are both induced by long-term potentiation and downregulated in the
aged brain. In addition to revitalizing other aged tissues, exposure to factors
in young blood counteracts age-related changes in these central nervous system
parameters, although the identities of specific cognition-promoting factors or
whether such activity exists in human plasma remains unknown. We hypothesized
that plasma of an early developmental stage, namely umbilical cord plasma,
provides a reservoir of such plasticity-promoting proteins. Here we show that
human cord plasma treatment revitalizes the hippocampus and improves cognitive
function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood
borne factor enriched in human cord plasma, young mouse plasma, and young mouse
hippocampi, appears in the brain after systemic administration and increases
synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion
experiments in aged mice revealed TIMP2 to be necessary for the cognitive
benefits conferred by cord plasma. We find that systemic pools of TIMP2 are
necessary for spatial memory in young mice, while treatment of brain slices with
TIMP2 antibody prevents long-term potentiation, arguing for previously unknown
roles for TIMP2 in normal hippocampal function. Our findings reveal that human
cord plasma contains plasticity-enhancing proteins of high translational value
for targeting ageing- or disease-associated hippocampal dysfunction.
PMID- 28424513
TI - Super-multiplex vibrational imaging.
AB - The ability to visualize directly a large number of distinct molecular species
inside cells is increasingly essential for understanding complex systems and
processes. Even though existing methods have successfully been used to explore
structure-function relationships in nervous systems, to profile RNA in situ, to
reveal the heterogeneity of tumour microenvironments and to study dynamic
macromolecular assembly, it remains challenging to image many species with high
selectivity and sensitivity under biological conditions. For instance,
fluorescence microscopy faces a 'colour barrier', owing to the intrinsically
broad (about 1,500 inverse centimetres) and featureless nature of fluorescence
spectra that limits the number of resolvable colours to two to five (or seven to
nine if using complicated instrumentation and analysis). Spontaneous Raman
microscopy probes vibrational transitions with much narrower resonances (peak
width of about 10 inverse centimetres) and so does not suffer from this problem,
but weak signals make many bio-imaging applications impossible. Although surface
enhanced Raman scattering offers high sensitivity and multiplicity, it cannot be
readily used to image specific molecular targets quantitatively inside live
cells. Here we use stimulated Raman scattering under electronic pre-resonance
conditions to image target molecules inside living cells with very high
vibrational selectivity and sensitivity (down to 250 nanomolar with a time
constant of 1 millisecond). We create a palette of triple-bond-conjugated near
infrared dyes that each displays a single peak in the cell-silent Raman spectral
window; when combined with available fluorescent probes, this palette provides 24
resolvable colours, with the potential for further expansion. Proof-of-principle
experiments on neuronal co-cultures and brain tissues reveal cell-type-dependent
heterogeneities in DNA and protein metabolism under physiological and
pathological conditions, underscoring the potential of this 24-colour (super
multiplex) optical imaging approach for elucidating intricate interactions in
complex biological systems.
PMID- 28424514
TI - Observed quantization of anyonic heat flow.
AB - The quantum of thermal conductance of ballistic (collisionless) one-dimensional
channels is a unique fundamental constant. Although the quantization of the
electrical conductance of one-dimensional ballistic conductors has long been
experimentally established, demonstrating the quantization of thermal conductance
has been challenging as it necessitated an accurate measurement of very small
temperature increase. It has been accomplished for weakly interacting systems of
phonons, photons and electronic Fermi liquids; however, it should theoretically
also hold in strongly interacting systems, such as those in which the fractional
quantum Hall effect is observed. This effect describes the fractionalization of
electrons into anyons and chargeless quasiparticles, which in some cases can be
Majorana fermions. Because the bulk is incompressible in the fractional quantum
Hall regime, it is not expected to contribute substantially to the thermal
conductance, which is instead determined by chiral, one-dimensional edge modes.
The thermal conductance thus reflects the topological properties of the
fractional quantum Hall electronic system, to which measurements of the
electrical conductance give no access. Here we report measurements of thermal
conductance in particle-like (Laughlin-Jain series) states and the more complex
(and less studied) hole-like states in a high-mobility two-dimensional electron
gas in GaAs-AlGaAs heterostructures. Hole-like states, which have fractional
Landau-level fillings of 1/2 to 1, support downstream charged modes as well as
upstream neutral modes, and are expected to have a thermal conductance that is
determined by the net chirality of all of their downstream and upstream edge
modes. Our results establish the universality of the quantization of thermal
conductance for fractionally charged and neutral modes. Measurements of anyonic
heat flow provide access to information that is not easily accessible from
measurements of conductance.
PMID- 28424515
TI - Structure and allosteric inhibition of excitatory amino acid transporter 1.
AB - Human members of the solute carrier 1 (SLC1) family of transporters take up
excitatory neurotransmitters in the brain and amino acids in peripheral organs.
Dysregulation of the function of SLC1 transporters is associated with
neurodegenerative disorders and cancer. Here we present crystal structures of a
thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1
(EAAT1), with and without allosteric and competitive inhibitors bound. The
structures reveal architectural features of the human transporters, such as intra
and extracellular domains that have potential roles in transport function,
regulation by lipids and post-translational modifications. The coordination of
the allosteric inhibitor in the structures and the change in the transporter
dynamics measured by hydrogen-deuterium exchange mass spectrometry reveal a
mechanism of inhibition, in which the transporter is locked in the outward-facing
states of the transport cycle. Our results provide insights into the molecular
mechanisms underlying the function and pharmacology of human SLC1 transporters.
PMID- 28424517
TI - Molecular genetics: Chaperone protein gets personal.
PMID- 28424516
TI - SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1
integrin.
AB - Cancer cells elude anti-tumour immunity through multiple mechanisms, including
upregulated expression of ligands for inhibitory immune checkpoint receptors.
Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic
blockade of signal regulatory protein (SIRP)-alpha, an inhibitory receptor on
macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour
cell elimination in vitro and in vivo, suggesting that blockade of the SIRPalpha
CD47 checkpoint could be useful in treating human cancer. However, the pro
phagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely
unknown. Here we find that macrophages are much more efficient at phagocytosis of
haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in
response to SIRPalpha-CD47 blockade. Using a mouse lacking the signalling
lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell
specific receptors, we determined that phagocytosis of haematopoietic tumour
cells during SIRPalpha-CD47 blockade was strictly dependent on SLAM family
receptors in vitro and in vivo. In both mouse and human cells, this function
required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319),
expressed on macrophages and tumour cell targets. In contrast to most SLAM
receptor functions, SLAMF7-mediated phagocytosis was independent of signalling
lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it
depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18, 19,
20) and utilize signals involving immunoreceptor tyrosine-based activation
motifs. These findings elucidate the mechanism by which macrophages engulf and
destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor
independent function for a SLAM receptor. Lastly, they suggest that patients with
tumours expressing SLAMF7 are more likely to respond to SIRPalpha-CD47 blockade
therapy.
PMID- 28424518
TI - The genetic basis of parental care evolution in monogamous mice.
AB - Parental care is essential for the survival of mammals, yet the mechanisms
underlying its evolution remain largely unknown. Here we show that two sister
species of mice, Peromyscus polionotus and Peromyscus maniculatus, have large and
heritable differences in parental behaviour. Using quantitative genetics, we
identify 12 genomic regions that affect parental care, 8 of which have sex
specific effects, suggesting that parental care can evolve independently in males
and females. Furthermore, some regions affect parental care broadly, whereas
others affect specific behaviours, such as nest building. Of the genes linked to
differences in nest-building behaviour, vasopressin is differentially expressed
in the hypothalamus of the two species, with increased levels associated with
less nest building. Using pharmacology in Peromyscus and chemogenetics in Mus, we
show that vasopressin inhibits nest building but not other parental behaviours.
Together, our results indicate that variation in an ancient neuropeptide
contributes to interspecific differences in parental care.
PMID- 28424519
TI - Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure.
AB - Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter
chromatin structure and nucleosome positions to allow regulatory proteins access
to DNA. Here we report the cryo-electron microscopy structure of chromatin
remodeller Switch/sucrose non-fermentable (SWI2/SNF2) from Saccharomyces
cerevisiae bound to the nucleosome. The structure shows that the two core domains
of Snf2 are realigned upon nucleosome binding, suggesting activation of the
enzyme. The core domains contact each other through two induced Brace helices,
which are crucial for coupling ATP hydrolysis to chromatin remodelling. Snf2
binds to the phosphate backbones of one DNA gyre of the nucleosome mainly through
its helicase motifs within the major domain cleft, suggesting a conserved
mechanism of substrate engagement across different remodellers. Snf2 contacts the
second DNA gyre via a positively charged surface, providing a mechanism to anchor
the remodeller at a fixed position of the nucleosome. Snf2 locally deforms
nucleosomal DNA at the site of binding, priming the substrate for the remodelling
reaction. Together, these findings provide mechanistic insights into chromatin
remodelling.
PMID- 28424520
TI - Decarboxylative alkenylation.
AB - Olefin chemistry, through pericyclic reactions, polymerizations, oxidations, or
reductions, has an essential role in the manipulation of organic matter. Despite
its importance, olefin synthesis still relies largely on chemistry introduced
more than three decades ago, with metathesis being the most recent addition. Here
we describe a simple method of accessing olefins with any substitution pattern or
geometry from one of the most ubiquitous and variegated building blocks of
chemistry: alkyl carboxylic acids. The activating principles used in amide-bond
synthesis can therefore be used, with nickel- or iron-based catalysis, to extract
carbon dioxide from a carboxylic acid and economically replace it with an
organozinc-derived olefin on a molar scale. We prepare more than 60 olefins
across a range of substrate classes, and the ability to simplify retrosynthetic
analysis is exemplified with the preparation of 16 different natural products
across 10 different families.
PMID- 28424522
TI - Animal behaviour: How to build a better dad.
PMID- 28424521
TI - Visualizing multistep elevator-like transitions of a nucleoside transporter.
AB - Membrane transporters move substrates across the membrane by alternating access
of their binding sites between the opposite sides of the membrane. An emerging
model of this process is the elevator mechanism, in which a substrate-binding
transport domain moves a large distance across the membrane. This mechanism has
been characterized by a transition between two states, but the conformational
path that leads to the transition is not yet known, largely because the available
structural information has been limited to the two end states. Here we present
crystal structures of the inward-facing, intermediate, and outward-facing states
of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we
determined the structures of multiple intermediate conformations, in which the
transport domain is captured halfway through its elevator motion. Our structures
present a trajectory of the conformational transition in the elevator model,
revealing multiple intermediate steps and state-dependent conformational changes
within the transport domain that are associated with the elevator-like motion.
PMID- 28424523
TI - Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl.
AB - Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and
cohesin into chromatin loops and topologically associated domains, which have
important roles in gene regulation and recombination. By binding to specific
sequences, CTCF defines contact points for cohesin-mediated long-range
chromosomal cis-interactions. Cohesin is also present at these sites, but has
been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops
until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites,
according to this or other models, is unknown. Here we show that the distribution
of cohesin in the mouse genome depends on transcription, CTCF and the cohesin
release factor Wings apart-like (Wapl). In CTCF-depleted fibroblasts, cohesin
cannot be properly recruited to CTCF sites but instead accumulates at
transcription start sites of active genes, where the cohesin-loading complex is
located. In the absence of both CTCF and Wapl, cohesin accumulates in up to 70
kilobase-long regions at 3'-ends of active genes, in particular if these converge
on each other. Changing gene expression modulates the position of these 'cohesin
islands'. These findings indicate that transcription can relocate mammalian
cohesin over long distances on DNA, as previously reported for yeast cohesin,
that this translocation contributes to positioning cohesin at CTCF sites, and
that active genes can be freed from cohesin either by transcription-mediated
translocation or by Wapl-mediated release.
PMID- 28424524
TI - HqiA, a novel quorum-quenching enzyme which expands the AHL lactonase family.
AB - The screening of a metagenomic library of 250,000 clones generated from a
hypersaline soil (Spain) allowed us to identify a single positive clone which
confers the ability to degrade N-acyl homoserine lactones (AHLs). The sequencing
of the fosmid revealed a 42,318 bp environmental insert characterized by 46 ORFs.
The subcloning of these ORFs demonstrated that a single gene (hqiA) allowed AHL
degradation. Enzymatic analysis using purified HqiA and HPLC/MS revealed that
this protein has lactonase activity on a broad range of AHLs. The introduction of
hqiA in the plant pathogen Pectobacterium carotovorum efficiently interfered with
both the synthesis of AHLs and quorum-sensing regulated functions, such as
swarming motility and the production of maceration enzymes. Bioinformatic
analyses highlighted that HqiA showed no sequence homology with the known
prototypic AHL lactonases or acylases, thus expanding the AHL-degrading enzymes
with a new family related to the cysteine hydrolase (CHase) group. The complete
sequence analysis of the fosmid showed that 31 ORFs out of the 46 identified were
related to Deltaproteobacteria, whilst many intercalated ORFs presented high
homology with other taxa. In this sense, hqiA appeared to be assigned to the
Hyphomonas genus (Alphaproteobacteria), suggesting that horizontal gene transfer
had occurred.
PMID- 28424525
TI - Genome-wide detection of copy number variation in Chinese indigenous sheep using
an ovine high-density 600 K SNP array.
AB - Copy number variants (CNVs) represent a form of genomic structural variation
underlying phenotypic diversity. In this study, we used the Illumina Ovine SNP
600 K BeadChip array for genome-wide detection of CNVs in 48 Chinese Tan sheep. A
total of 1,296 CNV regions (CNVRs), ranging from 1.2 kb to 2.3 Mb in length, were
detected, representing approximately 4.7% of the entire ovine genome (Oar_v3.1).
We combined our findings with five existing CNVR reports to generate a composite
genome-wide dataset of 4,321 CNVRs, which revealed 556 (43%) novel CNVRs.
Subsequently, ten novel CNVRs were randomly chosen for further quantitative real
time PCR (qPCR) confirmation, and eight were successfully validated. Gene
functional enrichment revealed that these CNVRs cluster into Gene Ontology (GO)
categories of homeobox and embryonic skeletal system morphogenesis. One CNVR
overlapping with the homeobox transcription factor DLX3 and previously shown to
be associated with curly hair in sheep was identified as the candidate CNV for
the special curly fleece phenotype in Tan sheep. We constructed a Chinese
indigenous sheep genomic CNV map based on the Illumina Ovine SNP 600 K BeadChip
array, providing an important addition to published sheep CNVs, which will be
helpful for future investigations of the genomic structural variations underlying
traits of interest in sheep.
PMID- 28424526
TI - The impact of host sex on the outcome of co-infection.
AB - Males and females vary in many characteristics that typically underlie how well a
host is able to fight infection, such as body-size, immune capacity, or energy
availability. Although well studied in the context of sexual signalling, there is
now growing recognition that these differences can influence aspects of pathogen
evolution as well. Here we consider how co-infection between multiple pathogen
strains is shaped by male-female differences. In natural populations, infections
by more than one pathogen strain or species are believed to be a widespread
occurrence. Using the water flea, Daphnia magna, we exposed genetically identical
males and females to replicated bacterial co-infections. We found that pathogen
transmission and virulence were much higher in females. However, males did not
simply lower average pathogen fitness, but rather the influence of co-infection
was more varied and less defined than in females. We discuss how pathogens may
have more fitness benefits to gain, and consequently to lose, when infecting one
sex over the other.
PMID- 28424527
TI - Unified Alignment of Protein-Protein Interaction Networks.
AB - Paralleling the increasing availability of protein-protein interaction (PPI)
network data, several network alignment methods have been proposed. Network
alignments have been used to uncover functionally conserved network parts and to
transfer annotations. However, due to the computational intractability of the
network alignment problem, aligners are heuristics providing divergent solutions
and no consensus exists on a gold standard, or which scoring scheme should be
used to evaluate them. We comprehensively evaluate the alignment scoring schemes
and global network aligners on large scale PPI data and observe that three
methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically
and biologically coherent alignments. We study the collective behaviour of
network aligners and observe that PPI networks are almost entirely aligned with a
handful of aligners that we unify into a new tool, Ulign. Ulign enables complete
alignment of two networks, which traditional global and local aligners fail to
do. Also, multiple mappings of Ulign define biologically relevant soft
clusterings of proteins in PPI networks, which may be used for refining the
transfer of annotations across networks. Hence, PPI networks are already well
investigated by current aligners, so to gain additional biological insights, a
paradigm shift is needed. We propose such a shift come from aligning all
available data types collectively rather than any particular data type in
isolation from others.
PMID- 28424528
TI - Elucidation of quantitative structural diversity of remarkable rearrangement
regions, shufflons, in IncI2 plasmids.
AB - A multiple DNA inversion system, the shufflon, exists in incompatibility (Inc) I1
and I2 plasmids. The shufflon generates variants of the PilV protein, a minor
component of the thin pilus. The shufflon is one of the most difficult regions
for de novo genome assembly because of its structural diversity even in an
isolated bacterial clone. We determined complete genome sequences, including
those of IncI2 plasmids carrying mcr-1, of three Escherichia coli strains using
single-molecule, real-time (SMRT) sequencing and Illumina sequencing. The
sequences assembled using only SMRT sequencing contained misassembled regions in
the shufflon. A hybrid analysis using SMRT and Illumina sequencing resolved the
misassembled region and revealed that the three IncI2 plasmids, excluding the
shufflon region, were highly conserved. Moreover, the abundance ratio of whole
shufflon structures could be determined by quantitative structural variation
analysis of the SMRT data, suggesting that a remarkable heterogeneity of whole
shufflon structural variations exists in IncI2 plasmids. These findings indicate
that remarkable rearrangement regions should be validated using both long-read
and short-read sequencing data and that the structural variation of PilV in the
shufflon might be closely related to phenotypic heterogeneity of plasmid-mediated
transconjugation involved in horizontal gene transfer even in bacterial clonal
populations.
PMID- 28424529
TI - Surface-dependent scenarios for dissolution-driven motion of growing droplets.
AB - Nano-droplets on a foreign substrate have received increasing attention because
of their technological possible applications, for instance to catalyse the growth
of nanowires. In some cases the droplets can move as a result of a reaction with
the substrate. In this work we show that the substrate orientation, the surface
morphology and the shape of the pits etched in the substrate by the droplets
affect the droplet motion, so that a single mechanism (droplet-induced substrate
dissolution) may lead to several unexpected droplet dynamics. The experiments are
carried out by low energy electron microscopy on Au-Si and Au-Ge, which are model
systems for studying liquid droplet alloys. Studying in-situ the behaviour of Au
droplets on various Si and Ge surfaces, we describe a subtle interplay between
the substrate orientation, the surface defects, and the droplet motion. Our
observations allow a deep understanding of the interfacial mechanisms at the
origin of the alloy formation and the associated droplet motion. These mechanisms
are based on events of substrate dissolution/recrystallization. The outcomes of
this work highlight the importance of the etching anisotropy on the droplet
substrate behaviours, and are essential in the perspective of positioning liquid
alloy droplets used for instance as nanowire catalysts.
PMID- 28424530
TI - Molecular diagnostic assays based on cpn60 UT sequences reveal the geographic
distribution of subgroup 16SrXIII-(A/I)I phytoplasma in Mexico.
AB - Geographically diverse samples from strawberry exhibiting symptoms of Strawberry
Green Petal (SbGP), periwinkle plants with virescence, and blackberry, blueberry,
and raspberry plants displaying yellowing and inedible fruits, were assayed for
the presence of phytoplasma DNA. PCR targeting the 16S rRNA-encoding gene and
chaperonin-60 (cpn60) showed that the plants were infected with phytoplasma
subgroup16SrXIII-(A/I)I (SbGP/MPV). To examine the geographic distribution of
this pathogen in Mexico, we designed an array of cpn60-targeted molecular
diagnostic assays for SbGP/MPV phytoplasma. A fluorescent microsphere
hybridization assay was designed that was capable of detecting SbGP/MPV
phytoplasma in infected plant tissues, successfully differentiating it from other
known phytoplasma cpn60 UT sequences, while identifying a double infection with
SbGP/MPV and aster yellows (16SrI) phytoplasma. Two quantitative assays,
quantitative real-time PCR (qRT-PCR) and droplet digital PCR (ddPCR), gave
similar results in infected samples. Finally, a loop-mediated isothermal
amplification (LAMP) assay provided rapid detection of SbGP/MPV phytoplasma DNA.
Application of these assays revealed that SbGP/MPV phytoplasma is widely
distributed in Central Mexico, with positive samples identified from eleven
localities within three states separated by hundreds of kilometres. These results
also provide tools for determining the presence and geographic distribution of
this pathogen in plant and insect samples in other localities.
PMID- 28424531
TI - Silicon Derived from Glass Bottles as Anode Materials for Lithium Ion Full Cell
Batteries.
AB - Every year many tons of waste glass end up in landfills without proper recycling,
which aggravates the burden of waste disposal in landfill. The conversion from un
recycled glass to favorable materials is of great significance for sustainable
strategies. Recently, silicon has been an exceptional anode material towards
large-scale energy storage applications, due to its extraordinary lithiation
capacity of 3579 mAh g-1 at ambient temperature. Compared with other quartz
sources obtained from pre-leaching processes which apply toxic acids and high
energy-consuming annealing, an interconnected silicon network is directly derived
from glass bottles via magnesiothermic reduction. Carbon-coated glass derived
silicon (gSi@C) electrodes demonstrate excellent electrochemical performance with
a capacity of ~1420 mAh g-1 at C/2 after 400 cycles. Full cells consisting of
gSi@C anodes and LiCoO2 cathodes are assembled and achieve good initial cycling
stability with high energy density.
PMID- 28424533
TI - The Radical Flank Effect and Cross-occupational Collaboration for Technology
Development during a Power Shift.
AB - This 12-month ethnographic study of an early entrant into the U.S. car-sharing
industry demonstrates that when an organization shifts its focus from developing
radical new technology to incrementally improving this technology, the shift may
spark an internal power struggle between the dominant engineering group and a
challenger occupational group such as the marketing group. Analyzing 42 projects
in two time periods that required collaboration between engineering and marketing
during such a shift, we show how cross-occupational collaboration under these
conditions can be facilitated by a radical flank threat, through which the
bargaining power of moderates is strengthened by the presence of a more-radical
group. In the face of a strong threat by radical members of a challenger
occupational group, moderate members of the dominant engineering group may change
their perceptions of their power to resist challengers' demands and begin to
distinguish between the goals of radical versus more-moderate challengers. To
maintain as much power as possible and prevent the more-dramatic change in
engineering occupational goals demanded by radical challengers, moderate
engineers may build a coalition with moderate challengers and collaborate for
incremental technology development.
PMID- 28424532
TI - Stemness and differentiation potential-recovery effects of sinapic acid against
ultraviolet-A-induced damage through the regulation of p38 MAPK and NF-kappaB.
AB - Ultraviolet A (UVA) irradiation exerts negative effects on stemness and
differentiation potential of stem cells. This study aimed to explore the effect
of sinapic acid on UVA-irradiation-induced damages to stemness and
differentiation potential of human-adipose-tissue-derived mesenchymal stem cells
(hAMSCs) and its UVA-antagonist mechanisms. Sinapic acid attenuated UVA-induced
reduction in the proliferative potential and stemness by upregulating OCT4, SOX2,
and NANOG. In addition, sinapic acid significantly recovered UVA-induced
reduction in expression level of hypoxia-inducible factor (HIF)-1alpha. The
antagonist effect of sinapic acid against stemness damage was mediated by
reduceing PGE2 production through inhibition of p38 MAPK and NF-kappaB. Moreover,
sinapic acid attenuated UVA-induced reduction in differentiation potential by
downregulating the expression of macrophage migration inhibitory factor (MIF) and
Kruppel-like factor (KLF) 2 gene while activating AMP-activated protein kinase
(AMPK). UVA-induced inhibition of adipogenic differentiation was mediated by
reducing MIF production through suppression of NF-kappaB. Taken together, these
findings suggest that sinapic acid may ameliorate UVA-irradiation-induced reduced
stemness and differentiation potential of hAMSCs. Therefore, sinapic acid might
have potential as an antagonist agent to attenuate damages caused by UVA.
PMID- 28424534
TI - Corneal flap thickness with the Moria M2 single-use head 90 microkeratome in 72
consecutive LASIK procedures.
AB - PURPOSE: This study aimed to evaluate the accuracy and consistency of corneal
flap thickness in laser-assisted in situ keratomileusis (LASIK) with the Moria M2
single-use head 90 microkeratome. METHODS: The central corneal thickness of 72
(37 right, 35 left) eyes of 37 patients was measured by ultrasonic pachymetry
preoperatively and intraoperatively after flap cut. The Moria M2 single-use head
90 microkeratome was used to create a superior hinged flap in all eyes. The right
eyes were always operated on before the left eyes in each patient, using the same
blade in all bilateral cases. All patients underwent LASIK for myopia and/or
myopic astigmatism using VISX Star S4 platform. RESULTS: The mean preoperative
spherical equivalent refraction was -3.55+/-2.30 D (range: -0.625 to -11.00 D),
preoperative central corneal thickness by ultrasonic pachymetry was 541+/-26.82
um (490-600 um) and steepest K was 44.08+/-1.49 D (40-46.75 D) in all eyes. The
mean flap thickness was 136.97+/-20.07 um (106-192 um), 131.2+/-19.5 um (91-192
um), and 134.16+/-19.85 um (91-192 um) in the right, left, and both eyes,
respectively. A positive significant relationship was found between flap
thickness and preoperative ultrasonic pachymetry thickness. No significant
relationship was found between flap thickness and the age, preoperative spherical
equivalent, and preoperative steepest K. The difference between the first and
second eyes was not significant. There were no major intraoperative and
postoperative complications in all eyes. CONCLUSION: The Moria M2 single-use head
90 microkeratome cut relatively thicker flaps than were intended. The flap
thickness range was quite wide. This was a disadvantage for the accuracy and
consistency of corneal flap thickness.
PMID- 28424535
TI - Human papillomavirus (HPV): systemic treatment with Gene-Eden-VIR/Novirin safely
and effectively clears virus.
AB - PURPOSE: This paper reports the results of a clinical study that tested the
effect of systemic treatment with the botanical product Gene-Eden-VIR/Novirin on
the clearance rate (also called time to clearance) of the human papillomavirus
(HPV). The study compared the clearance rate in treated and untreated individuals
suffering from a symptomatic HPV infection. The data on the untreated individuals
were obtained by reverse engineering of the Kaplan-Meier figures in five
published papers. MATERIALS AND METHODS: The study included 59 treated
participants. All participants were suffering from a symptomatic HPV infection
prior to the commencement of treatment. The treatment was one to four capsules of
Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-12 months. The
study included five groups of external controls with diverse characteristics.
RESULTS: The mean time to clearance in Gene-Eden-VIR/Novirin-treated individuals
was 5.1 months or 151.5 days (95% CI: 4.2-5.9 months or 95% CI: 125.7-177.3 days,
respectively). The median time to clearance was 3.5 months. The mean time to
clearance in the five untreated groups ranged from 6.9 to 20.0 months (P<0.0001
for the difference between treatment group and each untreated group). Also, 100%
of the participants in the treatment group were HPV free at the end of 12 months
vs 53%, 52%, 65%, 20%, and 77% in the untreated control groups. The treated
participants reported no adverse experiences. CONCLUSION: This clinical study has
two major contributions. First, it showed that systemic treatment with the
natural Gene-Eden-VIR/Novirin decreased the time to HPV clearance, increased the
percentage of HPV-free individuals, and caused no adverse experiences in
individuals suffering from a symptomatic HPV infection. Since there are no other
systemic treatments for symptomatic HPV infections, this study presents highly
valuable information on the clinical effects of the first treatment in this
category. Second, the study presents a new method for conducting clinical studies
that addresses one of the major deficiencies associated with the practice of the
randomized controlled trial method.
PMID- 28424536
TI - Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of
cavitary pulmonary tuberculosis: preparation and in vitro characterization.
AB - In this study, we aimed to design controlled-release microspheres for the
treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor
drug delivery and short duration maintained at effective drug concentration
during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid
loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in
water emulsion solvent evaporation method and assessed their in vitro release as
well as the bronchial mucosal retention characteristics. The microspheres are
spherical in shape with a circular concave on the surface. The particle size of
RLPMs was 27.38+/-1.28 MUm. The drug loading of rifapentine and linezolid was
18.51+/-0.26 and 8.42%+/-0.24%, respectively, while the encapsulation
efficiencies were 55.53+/-0.78 and 16.87%+/-0.47%, respectively (n=3). During the
burst release phase of the in vitro release test, 21.37%+/-0.68% rifapentine was
released in 3 days and 43.56%+/-2.54% linezolid was released in 1 day. Then, both
the drugs entered the sustained release phase. Finally, the cumulative percentage
release of rifapentine and linezolid in 14 days was 27.61+/-1.52 and 51.01%+/
3.31%, respectively (n=3). Bronchoscopic observation revealed that the controlled
release microspheres could slowly release the drugs and retain them on the
surface of bronchial mucosa of canines for 20 days. These results indicated that
the fabricated microspheres exhibited a significant sustained release effect and
could effectively retain the drugs on the surface of bronchial mucosa. Therefore,
this study provides a theoretical and practical foundation for the development of
fabricated microspheres loaded with multiple anti-TB drugs in the bronchoscopic
interventional therapy of cavity pulmonary TB.
PMID- 28424537
TI - Awake craniotomy anesthetic management using dexmedetomidine, propofol, and
remifentanil.
AB - INTRODUCTION: Awake craniotomy allows continuous monitoring of patients'
neurological functions during open surgery. Anesthesiologists have to sedate
patients in a way so that they are compliant throughout the whole surgical
procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently,
the use of alpha2-receptor agonist dexmedetomidine as the primary hypnotic
sedative medication is increasing. METHODS: Nine patients undergoing awake
craniotomy were treated with refined monitored anesthesia care (MAC) protocol
consisting of a combination of local anesthesia without scalp block, low-dose
infusion of dexmedetomidine, propofol, and remifentanil, without the need of
airways management. RESULTS: The anesthetic protocol applied in our study has the
advantage of decreasing the dose of each drug and thus reducing the occurrence of
side effects. All patients had smooth and rapid awakenings. The brain remained
relaxed during the entire procedure. CONCLUSION: In our experience, this protocol
is safe and effective during awake brain surgery. Nevertheless, prospective
randomized trials are necessary to confirm the optimal anesthetic technique to be
used.
PMID- 28424538
TI - Metal complexes in cancer therapy - an update from drug design perspective.
AB - In the past, metal-based compounds were widely used in the treatment of disease
conditions, but the lack of clear distinction between the therapeutic and toxic
doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg
in 1960, a milestone in the history of metal-based compounds used in the
treatment of cancers was witnessed. This forms the foundation for the modern era
of the metal-based anticancer drugs. Platinum drugs, such as cisplatin,
carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the
treatment of cancer, but the delay in the therapeutic accomplishment of other
metal-based compounds hampered the progress of research in this field. Recently,
however, there has been an upsurge of activities relying on the structural
information, aimed at improving and developing other forms of metal-based
compounds and nonclassical platinum complexes whose mechanism of action is
distinct from known drugs such as cisplatin. In line with this, many more metal
based compounds have been synthesized by redesigning the existing chemical
structure through ligand substitution or building the entire new compound with
enhanced safety and cytotoxic profile. However, because of increased emphasis on
the clinical relevance of metal-based complexes, a few of these drugs are
currently on clinical trial and many more are awaiting ethical approval to join
the trial. In this review, we seek to give an overview of previous reviews on the
cytotoxic effect of metal-based complexes while focusing more on newly designed
metal-based complexes and their cytotoxic effect on the cancer cell lines, as
well as on new approach to metal-based drug design and molecular target in cancer
therapy. We are optimistic that the concept of selective targeting remains the
hope of the future in developing therapeutics that would selectively target
cancer cells and leave healthy cells unharmed.
PMID- 28424539
TI - beta3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2
cells, which might further promote cholesterol efflux from macrophage foam cells.
AB - OBJECTIVE: The aim of this study was to explore the effects of beta3-adrenoceptor
(beta3-AR) activation on HepG2 cells and its influence on cholesterol efflux from
macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and
treated with the beta3-AR agonist, BRL37344, and antagonist, SR52390A, and the
expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and beta3-AR in the
supernatants and cells was determined. The expression of peroxisome proliferator
activated receptor (PPAR) gamma and PPARalpha in the HepG2 cells was also
assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed
the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol
content of the foam cells was also measured, and the cholesterol efflux from the
macrophages was examined by determining 3H-labeled cholesterol levels. Expression
of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam
cells was also assessed. RESULTS: beta3-AR activation increased ApoA-I expression
in both the HepG2 cells and the supernatants; PPARgamma expression was
upregulated, but PPARalpha expression was not. Treatment with GW9662 abolished
the increased expression of ApoA-I induced by the beta3-AR agonist. The HepG2
cell supernatants decreased the lipid accumulation and increased the cholesterol
efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1
expression, increased in the macrophage foam cells treated with BRL37344-treated
HepG2 cell supernatants. CONCLUSION: Activation of beta3-AR in HepG2 cells
upregulates ApoA-I expression, which might further promote cholesterol efflux
from macrophage foam cells. PPARgamma might be required for the induction of ApoA
I expression.
PMID- 28424540
TI - MC-PPEA as a new and more potent inhibitor of CLP-induced sepsis and pulmonary
inflammation than FK866.
AB - Our previous study indicated that overexpression of nicotinamide
phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown
of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found
that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which
the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed
a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the
effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced
sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP
induced mortality, serum tumor necrosis factor alpha (TNFalpha) levels, pulmonary
myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1beta
messenger RNA levels. In vitro cell permeability and electric cell-substrate
impedance sensing assays demonstrated that MC4 inhibited TNFalpha- and thrombin
mediated pulmonary endothelial cell permeability better than FK866. MC4 also
exerted more potent effects than FK866, at concentrations as low as 0.3 nM, to
attenuate TNFalpha-mediated intracellular cytokine expression, nicotinamide
adenine dinucleotide (NAD+) and its reduced form NADH levels, and nuclear factor
kappa B p65 phosphorylation and nuclear translocation in A549 cells. Our results
strongly suggest that the newly developed MC4 is a more potent suppressor of CLP
induced pulmonary inflammation and sepsis than FK866, with potential clinical
application as a new treatment agent for sepsis and inflammation.
PMID- 28424541
TI - Physician's recommendation and explanation is important in the initiation and
maintenance of allergen immunotherapy.
AB - BACKGROUND: Allergen immunotherapy (AIT) is currently the only immune-modifying
treatment for allergic disease. The clinical efficacy of AIT for the treatment of
allergic rhinitis and bronchial asthma is well documented. However, many factors
including inconvenience, cost, side effects, and adherence influence the
initiation and persistence of AIT, and patients lack knowledge and have
misconceptions about the treatment. OBJECTIVE: We evaluated the knowledge,
attitude, and satisfaction of patients who received AIT. METHODS: We conducted a
retrospective analysis of medical records of 167 patients who received AIT, and
compared the clinical characteristics between conventional immunotherapy (CIT)
and rush immunotherapy (RIT). Ninety-nine patients completed a questionnaire
survey. RESULTS: Of the total 167 patients, 65.9% (n=110) were treated with CIT
and 34.1% (n=57) with RIT. More than half of the patients (68.7%) initiated AIT
according to their physician's recommendation. Frequent hospital visits were the
main barrier for persistence of AIT. RIT patients were younger and started AIT
earlier than CIT patients. The majority (77%) of patients who received AIT were
satisfied, with no significant difference between CIT and RIT groups. RIT and
fewer allergens used in AIT were related with preference for AIT to
pharmacotherapy. The longer duration of AIT was associated with higher treatment
satisfaction. CONCLUSION: A majority of patients initiated AIT by the physician's
recommendation and were satisfied with treatment regardless of CIT or RIT
schedule. Adequate patient education and a strict patient-physician relationship
in early AIT period could improve the effectiveness and compliance of AIT.
PMID- 28424542
TI - Why do psychiatric patients stop antipsychotic medication? A systematic review of
reasons for nonadherence to medication in patients with serious mental illness.
AB - BACKGROUND: Antipsychotic medication reduces the severity of serious mental
illness (SMI) and improves patient outcomes only when medicines were taken as
prescribed. Nonadherence to the treatment of SMI increases the risk of relapse
and hospitalization and reduces the quality of life. It is necessary to
understand the factors influencing nonadherence to medication in order to
identify appropriate interventions. This systematic review assessed the published
evidence on modifiable reasons for nonadherence to antipsychotic medication in
patients with SMI. METHODS: Articles published between January 1, 2005, and
September 10, 2015, were searched on MEDLINE through PubMed. Abstracts were
independently screened by 2 randomly assigned authors for inclusion, and
disagreement was resolved by another author. Selected full-text articles were
divided among all authors for review. RESULTS: A qualitative analysis of data
from 36 articles identified 11 categories of reasons for nonadherence. Poor
insight was identified as a reason for nonadherence in 55.6% (20/36) of studies,
followed by substance abuse (36.1%, 13/36), a negative attitude toward medication
(30.5%, 11/36), medication side effects (27.8%, 10/36), and cognitive impairments
(13.4%, 7/36). A key reason directly associated with intentional nonadherence was
a negative attitude toward medication, a mediator of effects of insight and
therapeutic alliance. Substance abuse was the only reason consistently associated
with unintentional nonadherence, regardless of type and stage of SMI. DISCUSSION:
Although adherence research is inherently biased because of numerous
methodological limitations and specific reasons under investigation, reasons for
nonadherence consistently identified as significant across studies likely reflect
valid existing associations with important clinical implications. CONCLUSION:
This systematic review suggests that a negative attitude toward medication and
substance abuse are consistent reasons for nonadherence to antipsychotic
medication among people with SMI. Adherence enhancement approaches that
specifically target these reasons may improve adherence in a high-risk group.
However, it is also important to identify drivers of poor adherence specific to
each patient in selecting and implementing intervention strategies.
PMID- 28424543
TI - Patient perceptions of a comprehensive telemedicine intervention to address
persistent poorly controlled diabetes.
AB - OBJECTIVE: We studied a telemedicine intervention for persistent poorly
controlled diabetes mellitus (PPDM) that combined telemonitoring, self-management
support, and medication management. The intervention was designed for practical
delivery using existing Veterans Affairs (VA) telemedicine infrastructure. To
refine the intervention and inform the delivery of the intervention in other
settings, we examined participants' experiences. METHODS: We conducted
semistructured interviews with 18 Veterans who completed the intervention. We
analyzed interview text using directed content analysis and categorized themes by
hemoglobin A1c (HbA1c) improvement (<1% or >=1%). RESULTS: Participants generally
reported greater awareness of their blood glucose levels; however, they described
dissatisfaction with the telemonitoring interface and competing demands during
the intervention. Participants with <1% HbA1c improvement reported that these
challenges interfered with their engagement. Participants with >=1% HbA1c
improvement reported new self-management routines despite challenges. CONCLUSION:
Despite competing demands and frustration with the telemonitoring interface, many
participants demonstrated intervention engagement and substantial improvement in
HbA1c ($1%). Differences in engagement may reflect differing capacity to manage
treatment burden. Because it relies on existing infrastructure, this intervention
is a promising model for addressing PPDM within VA. Future work should focus on
optimizing systems' telemedicine infrastructure; while reliance on existing
infrastructure may facilitate practical delivery, and it may also limit
intervention engagement by excessively contributing to treatment burden.
PMID- 28424544
TI - Association of genetic variations in the mitochondrial DNA control region with
presbycusis.
AB - BACKGROUND: The prominent role of mitochondria in the generation of reactive
oxygen species, cell death, and energy production contributes to the importance
of this organelle in the intracellular mechanism underlying the progression of
the common sensory disorder of the elderly, presbycusis. Reduced mitochondrial
DNA (mtDNA) gene expression and coding region variation have frequently been
reported as being associated with the development of presbycusis. The mtDNA
control region regulates gene expression and replication of the genome of this
organelle. To comprehensively understand of the role of mitochondria in the
progression of presbycusis, we compared variations in the mtDNA control region
between subjects with presbycusis and controls. METHODS: A total of 58
presbycusis patients and 220 control subjects were enrolled in the study after
examination by the otolaryngologist and audiology tests. Variations in the mtDNA
control region were investigated by polymerase chain reaction and Sanger
sequencing. RESULTS: A total of 113 sequence variants were observed in mtDNA, and
variants were detected in 100% of patients, with 84% located in hypervariable
regions. The frequencies of the variants, 16,223 C>T, 16,311 T>C, 16,249 T>C, and
15,954 A>C, were significantly different between presbycusis and control
subjects. CONCLUSION: The statistically significant difference in the frequencies
of four nucleotide variants in the mtDNA control region of presbycusis patients
and controls is in agreement with previous experimental evidence and supports the
role of mitochondria in the intracellular mechanism underlying presbycusis
development. Moreover, these variants have potential as diagnostic markers for
individuals at a high risk of developing presbycusis. The data also suggest the
possible presence of changes in the mtDNA control region in presbycusis, which
could alter regulatory factor binding sites and influence mtDNA gene expression
and copy number.
PMID- 28424545
TI - Efficacy and safety of alcohol septal ablation in patients over 65 years old with
obstructive hypertrophic cardiomyopathy.
AB - BACKGROUND: The performance of alcohol septal ablation (ASA) in elderly
symptomatic patients with drug-refractory obstructive hypertrophic cardiomyopathy
is still to be confirmed. The objective of this study was to compare the efficacy
and safety of ASA in patients under and over 65 years old. METHODS AND RESULTS:
Fifty-one consecutive patients with obstructive hypertrophic cardio-myopathy who
underwent ASA were retrospectively included and reviewed for in-hospital major
acute cardiac events and follow-up. Twenty-eight patients were over 65 years old.
Left ventricular outflow tract obstruction at rest, use of diuretic and average
dose of diuretic were higher in patients over 65 years old. There was no
difference in hospital stay between patients under and over 65 years old. Among
patients over 65 years old, 2 (7%) died before being discharged. Major acute
cardiac events were more frequent in patients over 65 years old in comparison
with younger patients (43% versus 9%, respectively, P=0.007). The average follow
up duration was 16+/-15 months. There was no difference between patients under
and over 65 years old regarding the efficacy of the procedure with a decrease of
the New York Heart Association class of 1.3+/-0.6 and 1.4+/-0.7 (P=0.510) and the
maximum left ventricular outflow tract gradient of 86+/-57 and 81+/-36 mmHg
(P=0.733), respectively. CONCLUSION: Elderly patients have the same benefits as
younger patients after ASA but have more complications including mortality
events.
PMID- 28424546
TI - Perspectives of older people living in long-term care facilities and of their
family members toward advance care planning discussions: a systematic review and
thematic synthesis.
AB - OBJECTIVE: We aimed to search and synthesize qualitative studies exploring the
perspectives of older people living in long-term care facilities and of their
family members about advance care planning (ACP) discussions. METHODS: The
enhancing transparency in reporting the synthesis of qualitative research
(ENTREQ) framework was used to guide the review and report its results. PubMed,
CINAHL, and PsycINFO were searched for studies published between January 2000 and
November 2015. All included studies were assessed for comprehensiveness of
reporting, and a thematic synthesis of their results was performed. RESULTS: The
nine included studies differed in terms of qualitative method used,
comprehensiveness of reporting, and geographical origin. The thematic synthesis
led to the identification of four main themes: 1) plans already made; 2) end-of
life care and decision-making; 3) opinions and attitudes toward ACP; and 4) how,
when, about what, and with whom to do ACP. CONCLUSION: Despite their willingness
to be involved in a shared decision-making process, older residents and their
families still have little experience with ACP. PRACTICAL IMPLICATIONS: In view
of implementing ACP for elders living in long-term care facilities, it would be
important to rethink ACP and also to incorporate their nonmedical preferences,
according to their own priorities.
PMID- 28424547
TI - Omega-3 fatty acid supplementation can improve both symptoms and signs of dry eye
disease.
PMID- 28424548
TI - Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related
to emphysema associated with chronic obstructive pulmonary disease.
AB - BACKGROUND: Cigarette smoking-induced oxidant-antioxidant imbalance is a factor
that contributes to the pathogenesis of COPD through epithelial cell apoptosis.
Irisin is a skeletal muscle cell-derived myokine associated with physical
activity. Irisin is also known to decrease oxidant-induced apoptosis in patients
with diabetes mellitus. However, the correlation between irisin and emphysema in
COPD and its role in epithelial cell apoptosis remains unknown. SUBJECTS AND
METHODS: Forty patients with COPD were enrolled in this study. Pulmonary function
tests and measurements of the percentage of low-attenuation area on high
resolution computed tomography images were performed, and the results were
evaluated for correlation with serum irisin levels. The effect of irisin on
cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a
transcription factor for antioxidants, was also examined in vitro. RESULTS: Serum
irisin levels were significantly correlated with lung diffusing capacity for
carbon monoxide divided by alveolar volume (r=0.56, P<0.01) and percentage of low
attenuation area (r=-0.79, P<0.01). Moreover, irisin significantly enhanced Nrf2
expression (P<0.05) and reduced cigarette-smoke extract-induced A549 cell
apoptosis (P<0.05). CONCLUSION: Decreased serum irisin levels are related to
emphysema in patients with COPD and involved in epithelial apoptosis, resulting
in emphysema. Irisin could be a novel treatment for emphysema in patients with
COPD.
PMID- 28424549
TI - Seasonal variability in clinical care of COPD outpatients: results from the
Andalusian COPD audit.
AB - OBJECTIVES: Clinical practice in chronic obstructive pulmonary disease (COPD) can
be influenced by weather variability throughout the year. To explore the
hypothesis of seasonal variability in clinical practice, the present study
analyzes the results of the 2013-2014 Andalusian COPD audit with regard to
changes in clinical practice according to the different seasons. METHODS: The
Andalusian COPD audit was a pilot clinical project conducted from October 2013 to
September 2014 in outpatient respiratory clinics of hospitals in Andalusia, Spain
(8 provinces with more than 8 million inhabitants) with retrospective data
gathering. For the present analysis, astronomical seasons in the Northern
Hemisphere were used as reference. Bivariate associations between the different
COPD guidelines and the clinical practice changes over the seasons were explored
by using binomial multivariate logistic regression analysis with age, sex,
Charlson comorbidity index, type of hospital, and COPD severity by forced
expiratory volume in 1 second as covariates, and were expressed as odds ratio
(OR) with 95% confidence intervals (CIs). RESULTS: The Andalusian COPD audit
included 621 clinical records from 9 hospitals. After adjusting for covariates,
only inhaler device satisfaction evaluation was found to significantly differ
according to the seasons with an increase in winter (OR, 3.460; 95% CI, 1.469
8.151), spring (OR, 4.215; 95% CI, 1.814-9.793), and summer (OR, 3.371; 95% CI,
1.391-8.169) compared to that in autumn. The rest of the observed differences
were not significant after adjusting for covariates. However, compliance with
evaluating inhaler satisfaction was low. CONCLUSION: The various aspects of
clinical practice for COPD care were found to be quite homogeneous throughout the
year for the variables evaluated. Inhaler satisfaction evaluation, however,
presented some significant variation during the year. Inhaler device satisfaction
should be evaluated during all clinical visits throughout the year for improved
COPD management.
PMID- 28424551
TI - Interprofessional education for internationally educated health professionals: an
environmental scan.
AB - OBJECTIVE: The objective of this environmental scan was to identify Western
Canadian interprofessional education (IPE) resources that currently exist for
internationally educated health professionals (IEHPs). METHODOLOGY: A web-based
search was conducted to identify learning resources meeting defined inclusion
criteria with a particular focus on the resources available in the Western
Canadian provinces. Information was extracted using a standardized template, and
we contacted IEHP programs for additional information if necessary. Members of
the research team reviewed preliminary findings, identified missing information
from their respective provinces, and contacted organizations to fill in any gaps.
RESULTS: The scan identified 26 learning resources for IEHPs in Western Canadian
provinces and 15 in other provinces focused on support for IEHPs to meet their
profession-specific licensing requirements and to acquire knowledge and
competencies relevant to working in the Canadian health care system. Most
learning resources, such as those found in bridging programs for IEHPs, included
an orientation to the Canadian health care system, components of cultural
competence, and at least one aspect of interprofessional competence (eg,
communication skills). None of the 41 learning resources provided comprehensive
training for IEHPs to cover the six interprofessional competency domains defined
in the Canadian Interprofessional Health Collaborative (CIHC) National
Interprofessional Competency Framework. CONCLUSION: The IEHPs learning resources
in Western Canada do not cover all of the interprofessional competencies. This
review points to the value of developing a comprehensive IPE curriculum, based on
the six domains identified in the CIHC National Interprofessional Competency
Framework.
PMID- 28424550
TI - Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with
chitosan/alginate by layer by layer technology for antitumor applications.
AB - Natural polyelectrolyte multilayers of chitosan (CHI) and alginate (ALG) were
alternately deposited on doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid)
(PLGA) nanoparticles (NPs) with layer by layer self-assembly to control drug
release for antitumor activity. Numerous factors which influenced the multilayer
growth on nano-colloidal particles were studied: polyelectrolyte concentration,
NaCl concentration and temperature. Then the growth regime of the CHI/ALG
multilayers was elucidated. The coated NPs were characterized by transmission
electron microscopy, atomic force microscopy, X-ray diffraction and a zeta
potential analyzer. In vitro studies demonstrated an undesirable initial burst
release of DOX-loaded PLGA NPs (DOX-PLGA NPs), which was relieved from 55.12% to
5.78% through the use of the layer by layer technique. The release of DOX
increased more than 40% as the pH of media decreased from 7.4 to 5.0. More
importantly, DOX-PLGA (CHI/ALG)3 NPs had superior in vivo tumor inhibition rates
at 83.17% and decreased toxicity, compared with DOX-PLGA NPs and DOX in solution.
Thus, the presently formulated PLGA-polyelectrolyte NPs have strong potential
applications for numerous controlled anticancer drug release applications.
PMID- 28424552
TI - Prognostic value of circulating tumor cells in the peripheral blood of patients
with esophageal squamous cell carcinoma.
AB - OBJECTIVE: Circulating tumor cells (CTCs) of patients with malignant tumors can
be used as a prognostic marker. However, there are few relevant reports to date
on esophageal squamous cell carcinoma (ESCC). Our study assesses the clinical
significance of CTCs in ESCC patients. PATIENTS AND METHODS: CTCs were detected
in 103 peripheral blood (PB) samples from 59 ESCC patients. Correlation between
CTCs and clinical parameters was analyzed using the chi2 test or Fisher's exact
test. Overall survival (OS) and progression-free survival (PFS) were analyzed
using Kaplan-Meier analysis and univariate and multivariate methods. RESULTS: The
CTC detection rate was 79.7% (47/59) at baseline. The frequency of CTC-positive
patients increased as the disease stage advanced (88.0% in stages III-IV, 58.9%
in stages I-II). CTC counts >=0/7.5 mL of PB were correlated with the degree of
tumor differentiation, tumor infiltration, and lymph node and distant metastases.
Overall, the OS and PFS of patients with CTC counts >=3 or >=5/7.5 mL of PB
before surgery were significantly shorter than those of patients with CTC counts
<3 or <5/7.5 mL. Multivariate analysis showed CTC counts >=5/7.5 mL of PB to be a
strong prognostic indicator of OS (hazard ratio [HR] 12.478; 95% confidence
interval [CI], 8.2-34.3; P<0.05) and PFS (HR 6.524; 95% CI, 1.2-34.3; P<0.05) in
ESCC patients. Patients in whom CTCs changed from positive at baseline to a
negative value after surgery had an excellent prognosis. CONCLUSION: CTCs might
serve as a reference indicator for the prognosis and monitoring of disease
progression and treatment effects in ESCC.
PMID- 28424553
TI - The world of targeted therapies in kidney cancers: pitfalls, tips and tricks.
AB - In the past few years, metastatic renal cell carcinoma prognosis was improved by
the development of molecular targeted therapies (TTs). At the metastatic stage,
the tolerance to treatment is a major concern, not only because of the challenge
of the efficacy/toxicity ratio improvement but also because of the importance of
an optimal adherence to oral treatments. The present case series relates the
issues of dealing with uncommon and sometimes never described side effects of
sunitinib and sorafenib. The first case report deals with grade 3 vomiting during
hemodialysis with concurrent administration of sunitinib. The second case is an
iterative gout attack induced by sunitinib. The third case presents a grade 3
scalp dysesthesia with sorafenib. The fourth case includes an astonishing
efficacy of metronomic (ie, low doses during a long period of time) bevacizumab
in monotherapy. Multidisciplinary management and systematic reporting of
unexpected efficacies and toxicities are needed to better understand TTs real
therapeutic index. Although TTs revolutionized metastatic renal cell cancer
prognosis, they also brought about previously unknown side effects.
Identification and management of these off-target effects may be tricky, and
therefore, comedication must be wisely chosen. As the physiopathology of these
side effects is still unclear, multidisciplinary management and systematic
reporting of toxicities are essential.
PMID- 28424554
TI - Arterial stiffness in hematologic malignancies.
AB - Malignant and cardiovascular disorders are the top causes of mortality worldwide.
This article reviews the main literature data and mechanisms linking hematologic
malignancies and arterial stiffness, focusing on recent experimental and clinical
results. Several links were found in hematologic malignancies between complete
blood count and arterial stiffness. Chemotherapy, especially anthracyclines,
cyclophosphamide and tyrosine kinase inhibitors, as well as radiotherapy and
hematopoietic stem cell transplantation are the main known causes of arterial
stiffness increase in hematologic malignancies. The mechanisms of arterial
stiffness elevation in hematologic malignancies include an increased oxidative
stress, impaired vascular wall homeostasis, endothelial dysfunction and apoptosis
of endothelial cells, overexpression of inflammatory cytokines, accelerated
atherosclerosis, increased blood viscosity and unstable platelet aggregates.
Guidelines regarding cardiovascular health screening and cardiovascular risk
scores are necessary for hematologic cancer survivors in order to improve
prognosis and quality of life of the patients.
PMID- 28424555
TI - HMGB1 is negatively correlated with the development of endometrial carcinoma and
prevents cancer cell invasion and metastasis by inhibiting the process of
epithelial-to-mesenchymal transition.
AB - High-mobility group box protein 1 (HMGB1), a nuclear protein that plays a
significant role in DNA architecture and transcription, was correlated with the
progression of some types of cancer. However, the role of HMGB1 in endometrial
cancer cell invasion and metastasis remains unexplored. HMGB1 expression was
initially assessed by immunohistochemistry and reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) in normal endometrial tissue and endometrial
carcinoma tissue. High expressions of HMGB1 protein were detected in normal
endometrial tissues; however, in endometrial cancer tissues, the expressions of
HMGB1 were found to be very weak. Furthermore, HMGB1 expressions were negatively
correlated with advanced stage and lymph node metastasis in endometrial cancer.
Then by RT-qPCR, Western blot and immunocytochemistry, HMGB1 was also detected in
primary cultured endometrial cells and four kinds of endometrial cancer cell
lines (Ishikawa, HEC-1A, HEC-1B and KLE). We found that the expression of HMGB1
was much higher in normal endometrial cells than in endometrial cancer cells, and
reduced expression levels of HMGB1 were observed especially in the highly
metastatic cell lines. Using lentivirus transfection, HMGB1 small hairpin RNA was
constructed, and this infected the lowly invasive endometrial cancer cell lines,
Ishikawa and HEC-1B. HMGB1 knockdown significantly enhanced the proliferation,
invasion and metastasis of endometrial cancer cells and induced the process of
epithelial-to-mesenchymal transition. These results can contribute to the
development of a new potential therapeutic target for endometrial cancer.
PMID- 28424556
TI - Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role
for the androgen receptor pathway?
AB - The epidemic of insulin resistance, obesity, and metabolic syndrome has led to
the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of
liver disease in the US. Patients with NASH are at an increased risk for hepatic
disease-related morbidity and death, and chronic inflammation in NASH patients
can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in
males than in females, and genetic studies have identified androgen and androgen
receptors (ARs) as partially responsible for the gender disparity in the
development of liver disease and HCC. Although many factors are known to play
important roles in the progression of inflammation in NASH patients, the role of
androgen and AR in the progression of NASH to HCC has been understudied. This
review summarizes the evidence for a potential role of androgen and the AR
pathway in the development of NASH-related HCC and in the treatment of HCC. It
has been proposed that AR plays a role in the progression of HCC: inhibitory
roles in early stages of hepatocarcinogenesis and tumor-promoting roles in
advanced stages. AR can be activated by several pathways, even in the absence of
androgen. While AR has been explored as a potential therapeutic target in HCC,
several clinical trials have failed to demonstrate a clinical benefit of
antiandrogen drugs in HCC. This review discusses the potential reason for these
observations and discuss the potential future trials design in this important
setting.
PMID- 28424557
TI - Vedolizumab: toward a personalized therapy paradigm for people with ulcerative
colitis.
AB - Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory bowel
disease, with a characteristic leukocytic infiltration of the mucosa.
Immunosuppression including anti-TNF-alpha therapy is a mainstay of treatment for
many; however, systemic immunosuppression is not universally effective and is
associated with potential side effects. The gut-tropic integrin alpha4beta7,
which is expressed on leukocytes, mediates migration from the circulation to the
intestinal mucosa. Vedolizumab is a monoclonal antibody which blocks the egress
of leukocytes via alpha4beta7, preventing accumulation in the mucosa, and
attenuating inflammation without systemic immunosuppression. Vedolizumab has been
evaluated in UC in a phase III trial, demonstrating efficacy as both an induction
and a maintenance agent. In this article, we review the clinical trial data and
also explore the growing body of "real-world" effectiveness data, investigating
response and remission rates of vedolizumab in clinical practice. In addition, we
review the increasing volume of data supporting the reassuring safety profile
associated with vedolizumab.
PMID- 28424558
TI - Parents' relationship to pain during children's cancer treatment - a preliminary
validation of the Pain Flexibility Scale for Parents.
AB - OBJECTIVES: Pain is one of the most frequent and burdensome symptoms for children
with cancer. Psychological acceptance has been shown to be beneficial in chronic
pain. Acceptance-based interventions for experimentally induced pain have been
shown to predict increased pain tolerance and decreased pain intensity. An
acceptance-based pilot study for children with cancer experiencing pain has shown
promising results. Further, parental acceptance has been shown to predict
decreased child distress. To date, no instruments measuring acceptance in the
context of acute pain in children are available. The aim of this study was to
develop and evaluate an instrument to measure acceptance in parents of children
experiencing pain during cancer treatment. METHODS: A test version of the Pain
Flexibility Scale for Parents (PFS-P) was sent to parents of all children
undergoing cancer treatment in Sweden at the time of the study. Exploratory
factor analysis (n=243) examined numerous solutions. Internal consistency, test
retest reliability and convergent validity were calculated. RESULTS: A three
factor Promax solution best represented the data. The subscales were pain
resistance, valued action and pain fusion. Internal consistency was good
(alpha=0.81-0.93), and the total scale and the subscales demonstrated temporal
stability (r=0.76-0.87) and good convergent validity (-0.40 to -0.84).
DISCUSSION: The PFS-P measuring acceptance in parents of children experiencing
pain during cancer treatment is now available, enabling evaluation of acceptance
in the context of acute pain in children. The scale shows good psychometric
properties but needs further validation.
PMID- 28424559
TI - Evidence of both systemic inflammation and neuroinflammation in fibromyalgia
patients, as assessed by a multiplex protein panel applied to the cerebrospinal
fluid and to plasma.
AB - In addition to central hyperexcitability and impaired top-down modulation,
chronic inflammation probably plays a role in the pathophysiology of fibromyalgia
(FM). Indeed, on the basis of both animal experiments and human studies involving
the analysis of cytokines and other inflammation-related proteins in different
body fluids, neuroinflammatory mechanisms are considered to be central to the
pathophysiology of many chronic pain conditions. However, concerning FM, previous
human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked
only at a few predetermined cytokine candidates. Instead of analyzing only a few
substances at a time, we used a new multiplex protein panel enabling simultaneous
analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and
plasma inflammatory profiles of 40 FM patients compared with CSF from healthy
controls (n=10) and plasma from blood donor controls (n=46). Using multivariate
data analysis by projection, we found evidence of both neuroinflammation (as
assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two
groups of proteins (one for CSF and one for plasma) highly discriminating between
patients and controls are presented. Notably, we found high levels of CSF
chemokine CX3CL1 (also known as fractalkine). In addition, previous findings
concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first
time that such an extensive inflammatory profile has been described for FM
patients. Hence, FM seems to be characterized by objective biochemical
alterations, and the lingering characterization of its mechanisms as essentially
idiopathic or even psychogenic should be seen as definitively outdated.
PMID- 28424561
TI - Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine
plus atazanavir, with or without ritonavir, for 144 weeks.
AB - PURPOSE: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir
Induction with Epzicom Study (ARIES) were stratified by gender to compare
treatment responses. METHODS: A total of 369 HIV-infected, antiretroviral-naive
subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r)
whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to
maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within
treatment gender-related efficacy and safety differences were analyzed. RESULTS:
Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline
median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198
cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25
females/155 males) and most other demographics were similar between groups; more
females than males were black (65% vs 25%) and fewer females had baseline HIV-1
RNA >=100,000 copies/mL (41% vs 58%). At week 144, no significant differences
between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL
(ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r,
68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response
analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r,
+344 vs +301 cells/mm3); proportion with treatment-related grade 2-4 adverse
events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to
144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid
changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and
proportions completing the study were similar during the extension phase. Primary
withdrawal reasons were loss to follow-up and pregnancy for females and loss to
follow-up and other for males. CONCLUSION: Over 144 weeks, no significant gender
differences were observed in efficacy, safety, or fasting lipid changes with
abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r.
PMID- 28424560
TI - An exploratory study of host polymorphisms in genes that clinically characterize
breast cancer tumors and pretreatment cognitive performance in breast cancer
survivors.
AB - PURPOSE: Inspired by the hypothesis that heterogeneity in the biology of breast
cancers at the cellular level may account for cognitive dysfunction symptom
variability in survivors, the current study explored relationships between host
single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate
genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2,
ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4,
RRM2, and SCUBE2), identified from clinically relevant prognostic multigene
expression profiles for breast cancer, and pretreatment cognitive performance.
PATIENTS AND METHODS: The sample (n=220) was comprised of 138 postmenopausal
women newly diagnosed with early stage breast cancer and 82 postmenopausal age-
and education-matched healthy controls without breast cancer. Cognitive
performance was assessed after primary surgery but prior to initiation of
adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of
neuropsychological tests encompassing eight cognitive function composite domains:
attention, concentration, executive function, mental flexibility, psychomotor
speed, verbal memory, visual memory, and visual working memory. In total, 131
SNPs were included in the analysis. Standard and robust multiple linear
regression modeling was used to examine relationships between each domain and the
presence or absence of one or more minor alleles for each SNP. Genetic
risk/protection scores (GRSs) were calculated for each domain to evaluate the
collective effect of possession of multiple risk/protective alleles. RESULTS:
With the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main
effect and/or SNP by future prescribed treatment group interactions were observed
for every gene between at least one domain and one or more SNPs. All GRSs were
found to be significantly (P<0.001) associated with each respective domain score.
CONCLUSION: Associations between host SNPs and computed GRSs and variability in
pretreatment cognitive function performance support the study hypothesis, and
warrant further investigations to identify biomarkers for breast cancer-related
cognitive dysfunction.
PMID- 28424562
TI - Immunological and hematological reference intervals among HIV-seronegative
pregnant women in northwest Ethiopia.
AB - BACKGROUND: Pregnancy is a state characterized by profound physiological
hematological changes. However, hematological reference intervals being used in
clinical practice in Ethiopia are derived from nonlocal general populations,
despite the significant variations reported previously. The aim of this study was
to determine the immunological and hematological reference intervals in healthy
pregnancy among HIV-seronegative pregnant women in northwest Ethiopia. MATERIALS
AND METHODS: A total of 200 healthy, HIV-seronegative pregnant women were
enrolled from February 2015 to June 2015 in a cross-sectional study setting at
Gondar University Hospital. Sociodemographic and obstetric data were collected
using a structured questionnaire. Blood samples collected from each participant
were used to define the immunological and hematological parameters. The mean,
median, and 95% interval values were calculated for the immunological and
hematological parameters. P-value <0.05 was considered statistically significant
for all variables. RESULTS: This study found that there were changes in CD4+ T
cell count, platelet count, and hematocrit (HCT) values as pregnancy advances.
The calculated combined reference intervals for the absolute CD4+ T-cell count
and platelet count were 712.47-760.67 and 221.25-240.14, respectively. A
progressive decline in the platelet count was observed as pregnancy advanced,
with 95% intervals of 224.53-253.21, 209.50-237.38, and 213.70-247.86 in the
first, second, and third trimesters, respectively (P=0.27). There was a
statistically significant increase in mean (+/-standard deviation [SD]) HCT with
gestational age, being 39.18+/-6.70, 41.96+/-3.70, and 40.53+/-3.77 in the first,
second, and third trimesters, respectively (P=0.03). The overall 95% interval for
hemoglobin (HB) concentration was 12.99-13.36 g/dL, HCT 40.19%-41.49%, mean
corpuscular volume (MCV) 93.33-94.63 fL, and mean corpuscular hemoglobin (MCH)
28.88-34.81 pg. Compared with the reference ranges derived from other studies, we
found considerable variations in CD4+T-cell count, HB, HCT, and MCV values.
CONCLUSION: The findings of this study highlight the differences in
immunohematological profile among pregnant women and nonpregnant women from
Ethiopia and other countries, in addition to suggesting the need for such
establishment of local reference values for different populations.
PMID- 28424563
TI - Traumatic reopening of macular hole following successful surgical repair.
AB - A 75-year-old Caucasian female with a full-thickness macular hole underwent a
successful surgical repair. Vision improved from 20/400 to 20/30 after surgery.
Two years later, the patient presented with a decreased vision after a fall onto
her face with a reopened full-thickness macular hole. Vision decreased to 20/400
and then she underwent a second surgery with an internal limiting membrane
peeling, which resulted in a second successful closure of her macular hole.
Vision following the second surgery was 20/100. Reopening of a surgically
repaired macular hole commonly follows cataract surgery, epiretinal membrane
formation, and development of cystoid macular edema. This case demonstrates that
surgically repaired macular holes may reopen after trauma as well.
PMID- 28424564
TI - New developments in the management of narcolepsy.
AB - Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%
0.18% of the US and Western European populations. Genetic predisposition is
suspected because of narcolepsy's strong association with HLA DQB1*06-02, and
genome-wide association studies have identified polymorphisms in T-cell receptor
loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin
producing neurons; an autoimmune etiology possibly triggered by some
environmental agent may precipitate hypocretin neuronal loss. Current treatment
modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and
cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic
hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of gamma
hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help
sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various
antidepressant medications including norepinephrine serotonin reuptake
inhibitors, selective serotonin reuptake inhibitors, and tricyclic
antidepressants are second-line agents for treating cataplexy. In addition to
SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line
agents for EDS are stimulants such as methylphenidate and extended-release
amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin
based treatments, and immunotherapy to prevent hypocretin neuronal death. Non
hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649,
tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP
386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release
formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical
trials are investigating efficacy and safety of SXB, modafinil, and armodafinil
in children. gamma-amino butyric acid (GABA) modulation with GABAA receptor
agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs
investigated include GABAB agonists (baclofen), melanin-concentrating hormone
antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based
therapies include hypocretin peptide replacement administered either through an
intracerebroventricular route or intranasal route. Hypocretin neuronal transplant
and transforming stem cells into hypothalamic neurons are also discussed in this
article. Immunotherapy to prevent hypocretin neuronal death is reviewed.
PMID- 28424565
TI - Invasive Pneumococcal Disease: Still Lots to Learn and a Need for Standardized
Data Collection Instruments.
AB - Background. Large studies of invasive pneumococcal disease (IPD) are frequently
lacking detailed clinical information. Methods. A population-based 15-year study
of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years
formed the study group. Males outnumbered females and Aboriginal and homeless
persons were overrepresented. High rates of smoking, excessive alcohol use, and
illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had
functional limitations prior to admission. Bacteremia, pneumonia, and meningitis
were the most common major manifestations of IPD. Almost half of the patients had
alteration of mental status at the time of admission and 22% required mechanical
ventilation. Myocardial infarction, pulmonary embolism, and new onset stroke
occurred in 1.7, 1.3, and 1.1% of the patients, respectively; of those who had
echocardiograms, 35% had impaired ventricular function. The overall in-hospital
mortality was 15.6%. Conclusions. IPD remains a serious infection in adults. In
addition to immunization, preventative measures need to consider the
sociodemographic features more carefully. A standard set of data need to be
collected so that comparisons can be made from study to study. Future
investigations should target cardiac function and pulmonary embolism prevention
in this population.
PMID- 28424566
TI - Influence of organic molecules on the aggregation of TiO2 nanoparticles in acidic
conditions.
AB - Engineered nanoparticles released into the environment may interact with natural
organic matter (NOM). Surface complexation affects the surface potential, which
in turn may lead to aggregation of the particles. Aggregation of synthetic TiO2
(anatase) nanoparticles in aqueous suspension was investigated at pH 2.8 as a
function of time in the presence of various organic molecules and Suwannee River
fulvic acid (SRFA), using dynamic light scattering (DLS) and high-resolution
transmission electron microscopy (TEM). Results showed that the average
hydrodynamic diameter and zeta-potential were dependent on both concentration and
molecular structure of the organic molecule. Results were also compared with
those of quantitative batch adsorption experiments. Further, a time study of the
aggregation of TiO2 nanoparticles in the presence of 2,3-dihydroxybenzoic acid
(2,3-DHBA) and SRFA, respectively, was performed in order to observe changes in
zeta-potential and particle size over a time period of 9 months. In the 2,3-DHBA
TiO2 system, zeta-potentials decreased with time resulting in charge
neutralization and/or inversion depending on ligand concentration. Aggregate
sizes increased initially to the micrometer size range, followed by
disaggregation after several months. No or very little interaction between SRFA
and TiO2 occurred at the lowest concentrations tested. However, at the higher
concentrations of SRFA, there was an increase in both aggregate size and the
amount of SRFA adsorbed to the TiO2 surface. This was in correlation with the
zeta-potential that decreased with increased SRFA concentration, leading to
destabilization of the system. These results stress the importance of performing
studies over both short and long time periods to better understand and predict
the long-term effects of nanoparticles in the environment.
PMID- 28424567
TI - Access Barriers to Services by Immigrant Mothers of Children with Autism in
Canada.
AB - Equal access for autism services remains suboptimal for diverse groups. In
Canada, little is known about the barriers immigrant mothers face accessing
services and support for their children with developmental disabilities. In this
qualitative study, 21 immigrant mothers of children with Autism, from a diverse
ethno cultural background, were interviewed in Toronto, Canada. We apply House's
(1981) four domains of social support to analyze findings. Structural support
challenges, such as delays in diagnosis, fragmented and dispersed services were
common, followed by instrumental challenges due to loss of social ties and
stigma. Lack of expected support from partners, and negative perceptions of
services, were identified as emotional and perceptive challenges. Focused
attention is required to address inequalities within the context of current
access pathways for autism.
PMID- 28424568
TI - Teacher Awareness and Attitudes Regarding Adolescent Risk Behaviours: a Sample of
Finnish Middle and High School Teachers.
AB - Empirical evidence has shown that youth gamble on both regulated and unregulated
games, despite legislative prohibitions. This study assesses middle and high
school teachers' awareness and attitudes regarding adolescent gambling and other
potentially high-risk behaviours in Finland. A convenience sample of teachers (N
= 157) from 13 provinces participated in the survey. The results suggest that
teachers in Finland were more knowledgeable of the age limits of other adolescent
high-risk behaviours than the legal age for gambling. Teachers were somewhat
familiar with the behaviours and consequences associated with adolescent
gambling. All other risk behaviours were perceived as being more important than
gambling. Teachers' awareness about gambling prevention material in Finnish
schools was limited. Results suggest that initiatives are required to enhance
teachers' knowledge of adolescent problem gambling and its harmful short- and
long-term consequences. School policies and guidelines including gambling
behavior should be implemented in middle and high schools globally.
PMID- 28424570
TI - NANOTECHNOLOGY, NANOMEDICINE; ETHICAL ASPECTS.
AB - Nanotechnology is a field that we often hear of its name nowadays. Altough what
we know about it is soo poor, we admire this field of technlogy, moreover some
societies even argues that nanotechnology will cause second endustrial
revolution. In addition, nanotechnology makes our basic scientific knowledge
upside down and is soo powerfull that it is potent in nearly every scientific
field. Thereby, it is imposible to say that nanotechnology; which is soo
effective on human and human life; will not cause social and ethical outcomes. In
general, the definition of nanotechnology is the reconfiguration of nanomaterials
by human; there also are different definitions according to the history of
nanotechnology and different point of views. First of all, in comparison to the
other tehnology fields, what is the cause of excellence of nanotechnology, what
human can do is to foresee the advantages and disadvantages of it, what are the
roles of developed and developping countries for the progression of
nanotechnology, what is the attitude of nanoethics and what is view of global
politics to nanotechological research according to international regulations are
all the focus of interests of this study. Last but not least, our apprehension
capacity of nanotechnology, our style of adoption and evaluation of it and the
way that how we locate nanotechnology in our lifes and ethical values are the
other focus of interests.
PMID- 28424569
TI - Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine)
as a medicinal plant species: a review on the bioactive components,
pharmacological properties, analytical and biotechnological studies.
AB - Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been
well known in Far Eastern medicine for a long time. However, schisandra seems to
be a plant still underestimated in contemporary therapy still in the countries of
East Asia. The article presents latest available information on the chemical
composition of this plant species. Special attention is given to dibenzo
cyclooctadiene lignans. In addition, recent studies of the biological activity of
dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated.
The paper gives a short resume of their beneficial effects in biological systems
in vitro, in animals, and in humans, thus underlining their medicinal potential.
The cosmetic properties are depicted, too. The analytical methods used for
assaying schisandra lignans in the scientific studies and also in industry are
also presented. Moreover, special attention is given to the information on the
latest biotechnological studies of this plant species. The intention of this
review is to contribute to a better understanding of the huge potential of the
pharmacological relevance of S. chinensis.
PMID- 28424572
TI - Functional Sensitivity of 2D Simultaneous Multi-Slice Echo-Planar Imaging:
Effects of Acceleration on g-factor and Physiological Noise.
AB - Accelerated data acquisition with simultaneous multi-slice (SMS) imaging for
functional MRI studies leads to interacting and opposing effects that influence
the sensitivity to blood oxygen level-dependent (BOLD) signal changes. Image
signal to noise ratio (SNR) is decreased with higher SMS acceleration factors and
shorter repetition times (TR) due to g-factor noise penalties and saturation of
longitudinal magnetization. However, the lower image SNR is counteracted by
greater statistical power from more samples per unit time and a higher temporal
Nyquist frequency that allows for better removal of spurious non-BOLD high
frequency signal content. This study investigated the dependence of the BOLD
sensitivity on these main driving factors and their interaction, and provides a
framework for evaluating optimal acceleration of SMS-EPI sequences. functional
magnetic resonance imaging (fMRI) data from a scenes/objects visualization task
was acquired in 10 healthy volunteers at a standard neuroscience resolution of 3
mm on a 3T MRI scanner. SMS factors 1, 2, 4, and 8 were used, spanning TRs of
2800 ms to 350 ms. Two data processing methods were used to equalize the number
of samples over the SMS factors. BOLD sensitivity was assessed using g-factors
maps, temporal SNR (tSNR), and t-score metrics. tSNR results show a dependence on
SMS factor that is highly non-uniform over the brain, with outcomes driven by g
factor noise amplification and the presence of high frequency noise. The t-score
metrics also show a high degree of spatial dependence: the lower g-factor noise
area of V1 shows significant improvements at higher SMS factors; the moderate
level g-factor noise area of the parahippocampal place area shows only a trend of
improvement; and the high g-factor noise area of the ventral-medial pre-frontal
cortex shows a trend of declining t-scores at higher SMS factors. This spatial
variability suggests that the optimal SMS factor for fMRI studies is region
dependent. For task fMRI studies done with similar parameters as were used here
(3T scanner, 32-channel RF head coil, whole brain coverage at 3 mm isotropic
resolution), we recommend SMS accelerations of 4x (conservative) to 8x
(aggressive) for most studies and a more conservative acceleration of 2x for
studies interested in anterior midline regions.
PMID- 28424573
TI - Global Sensory Qualities and Aesthetic Experience in Music.
AB - A well-known tradition in the study of visual aesthetics holds that the
experience of visual beauty is grounded in global computational or statistical
properties of the stimulus, for example, scale-invariant Fourier spectrum or self
similarity. Some approaches rely on neural mechanisms, such as efficient
computation, processing fluency, or the responsiveness of the cells in the
primary visual cortex. These proposals are united by the fact that the
contributing factors are hypothesized to be global (i.e., they concern the
percept as a whole), formal or non-conceptual (i.e., they concern form instead of
content), computational and/or statistical, and based on relatively low-level
sensory properties. Here we consider that the study of aesthetic responses to
music could benefit from the same approach. Thus, along with local features such
as pitch, tuning, consonance/dissonance, harmony, timbre, or beat, also global
sonic properties could be viewed as contributing toward creating an aesthetic
musical experience. Several such properties are discussed and their neural
implementation is reviewed in the light of recent advances in neuroaesthetics.
PMID- 28424574
TI - Present Molecular Limitations of ON-Bipolar Cell Targeted Gene Therapy.
AB - Recent studies have demonstrated the safety and efficacy of ocular gene therapy
based on adeno-associated viral vectors (AAVs). Accordingly, a surge in promising
new gene therapies is entering clinical trials, including the first optogenetic
therapy for vision restoration. To date, optogenetic therapies for vision
restoration target either the retinal ganglion cells (GCs) or presynaptic ON
bipolar cells (OBCs). Initiating light responses at the level of the OBCs has
significant advantages over optogenetic activation of GCs. For example, important
neural circuitries in the inner retina, which shape the receptive fields of GCs,
remain intact when activating the OBCs. Current drawbacks of AAV-mediated gene
therapies targeting OBCs include (1) a low transduction efficiency, (2) off
target expression in unwanted cell populations, and (3) a poor performance in
human tissue compared to the murine retina. Here, we examined side-by-side the
performance of three state-of-the art AAV capsid variants, AAV7m8, AAVBP2, and
AAV7m8(Y444F) in combination with the 4xGRM6-SV40 promoter construct in the
healthy and degenerated mouse retina and in human post-mortem retinal explants.
We find that (1) the 4xGRM6-SV40 promoter is not OBC specific, (2) that all AAV
variants possess broad cellular transduction patterns, with differences between
the transduction patterns of capsid variants AAVBP2 and AAV7m8 and, most
importantly, (3) that all vectors target OBCs in healthy tissue but not in the
degenerated rd1 mouse model, potentially limiting the possibilities for an OBC
targeted optogenetic therapy for vision restoration in the blind.
PMID- 28424571
TI - Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma.
AB - Axons can be several orders of magnitude longer than neural somas, presenting
logistical difficulties in cargo trafficking and structural maintenance. Keeping
the axon compartment well supplied with energy also presents a considerable
challenge; even seemingly subtle modifications of metabolism can result in
functional deficits and degeneration. Axons require a great deal of energy, up to
70% of all energy used by a neuron, just to maintain the resting membrane
potential. Axonal energy, in the form of ATP, is generated primarily through
oxidative phosphorylation in the mitochondria. In addition, glial cells
contribute metabolic intermediates to axons at moments of high activity or
according to need. Recent evidence suggests energy disruption is an early
contributor to pathology in a wide variety of neurodegenerative disorders
characterized by axonopathy. However, the degree to which the energy disruption
is intrinsic to the axon vs. associated glia is not clear. This paper will review
the role of energy availability and utilization in axon degeneration in glaucoma,
a chronic axonopathy of the retinal projection.
PMID- 28424575
TI - Contribution of Autonomic Reflexes to the Hyperadrenergic State in Heart Failure.
AB - Heart failure (HF) is a complex syndrome representing the clinical endpoint of
many cardiovascular diseases of different etiology. Given its prevalence,
incidence and social impact, a better understanding of HF pathophysiology is
paramount to implement more effective anti-HF therapies. Based on left ventricle
(LV) performance, HF is currently classified as follows: (1) with reduced
ejection fraction (HFrEF); (2) with mid-range EF (HFmrEF); and (3) with preserved
EF (HFpEF). A central tenet of HFrEF pathophysiology is adrenergic hyperactivity,
featuring increased sympathetic nerve discharge and a progressive loss of
rhythmical sympathetic oscillations. The role of reflex mechanisms in sustaining
adrenergic abnormalities during HFrEF is increasingly well appreciated and
delineated. However, the same cannot be said for patients affected by HFpEF or
HFmrEF, whom also present with autonomic dysfunction. Neural mechanisms of
cardiovascular regulation act as "controller units," detecting and adjusting for
changes in arterial blood pressure, blood volume, and arterial concentrations of
oxygen, carbon dioxide and pH, as well as for humoral factors eventually released
after myocardial (or other tissue) ischemia. They do so on a beat-to-beat basis.
The central dynamic integration of all these afferent signals ensures
homeostasis, at rest and during states of physiological or pathophysiological
stress. Thus, the net result of information gathered by each controller unit is
transmitted by the autonomic branch using two different codes: intensity and
rhythm of sympathetic discharges. The main scope of the present article is to (i)
review the key neural mechanisms involved in cardiovascular regulation; (ii)
discuss how their dysfunction accounts for the hyperadrenergic state present in
certain forms of HF; and (iii) summarize how sympathetic efferent traffic reveal
central integration among autonomic mechanisms under physiological and
pathological conditions, with a special emphasis on pathophysiological
characteristics of HF.
PMID- 28424576
TI - Defensive Vocalizations and Motor Asymmetry Triggered by Disinhibition of the
Periaqueductal Gray in Non-human Primates.
AB - Rapid and reflexive responses to threats are present across phylogeny. The neural
circuitry mediating reflexive defense reactions has been well-characterized in a
variety of species, for example, in rodents and cats, the detection of and
species-typical response to threats is mediated by a network of structures
including the midbrain tectum (deep and intermediate layers of the superior
colliculus [DLSC]), periaqueductal gray (PAG), and forebrain structures such as
the amygdala and hypothalamus. However, relatively little is known about the
functional architecture of defense circuitry in primates. We have previously
reported that pharmacological activation of the DLSC evokes locomotor asymmetry,
defense-associated vocalizations, cowering behavior, escape responses, and attack
of inanimate objects (Holmes et al., 2012; DesJardin et al., 2013; Forcelli et
al., 2016). Here, we sought to determine if pharmacological activation of the PAG
would induce a similar profile of responses. We activated the PAG in three awake,
behaving macaques by microinfusion of GABA-A receptor antagonist, bicuculline
methiodide. Activation of PAG evoked defense-associated vocalizations and
postural/locomotor asymmetry, but not motor defense responses (e.g., cowering,
escape behavior). These data suggest a partial dissociation between the role of
the PAG and the DLSC in the defense network of macaques, but a general
conservation of the role of PAG in defense responses across species.
PMID- 28424577
TI - Investigation of Endocytic Pathways for the Internalization of Exosome-Associated
Oligomeric Alpha-Synuclein.
AB - Misfolding and aggregation of alpha-synuclein (alphasyn) resulting in
cytotoxicity is a hallmark of Parkinson's disease (PD) and related
synucleinopathies. The recent body of evidence indicates that alphasyn can be
released from neuronal cells by nonconventional exocytosis involving
extracellular vesicles (EVs) such as exosomes. The transfer of alphasyn between
cells has been proposed to be an important mechanism of disease propagation in
PD. To date, exosome trafficking mechanisms, including release and cell-cell
transmission, have not been fully described. To gain insight into the mechanisms
involved, exosomes were purified from conditioned media of stable cells secreting
alphasyn oligomers. A novel bimolecular protein complementation assay was used to
detect exosomes containing alphasyn oligomers. Recipient cells were treated with
exosomes containing alphasyn oligomers or "free" non-exosome-associated alphasyn
oligomers and internalization was monitored. We demonstrate that cell-derived
exosome-associated alphasyn oligomers can be efficiently internalized by
recipient cells. Interestingly exosome-free alphasyn oligomers isolated from
conditioned medium were not internalized but remained bound to the extracellular
surface. To investigate the endocytic pathway(s) required for the exosome uptake
different pharmacological inhibitors of caveolin-dependent, clathrin-dependent,
and macropinocytosis pathways were utilized. Surprisingly, none of these pathways
appear to play a significant role in the internalization of exosome-associated
alphasyn oligomers. Finally, the role of heparin sulfate proteoglycans (HSPGs) in
exosome-associated alphasyn internalization was investigated using genetic
approach. Despite previous studies showing HSPGs can modulate internalization of
fibrillar alphasyn, genetic manipulations did not attenuate internalization of
exosome-associated alphasyn oligomers in our hands, suggesting that exosome
associated alphasyn is internalized via an alternative endocytic pathway(s) that
has yet to be elucidated.
PMID- 28424578
TI - The CRB1 Complex: Following the Trail of Crumbs to a Feasible Gene Therapy
Strategy.
AB - Once considered science fiction, gene therapy is rapidly becoming scientific
reality, targeting a growing number of the approximately 250 genes linked to
hereditary retinal disorders such as retinitis pigmentosa and Leber's congenital
amaurosis. Powerful new technologies have emerged, leading to the development of
humanized models for testing and screening these therapies, bringing us closer to
the goal of personalized medicine. These tools include the ability to
differentiate human induced pluripotent stem cells (iPSCs) to create a "retina-in
a-dish" model and the self-formed ectodermal autonomous multi-zone, which can
mimic whole eye development. In addition, highly specific gene-editing tools are
now available, including the CRISPR/Cas9 system and the recently developed
homology-independent targeted integration approach, which allows gene editing in
non-dividing cells. Variants in the CRB1 gene have long been associated with
retinopathies, and more recently the CRB2 gene has also been shown to have
possible clinical relevance with respect to retinopathies. In this review, we
discuss the role of the CRB protein complex in patients with retinopathy. In
addition, we discuss new opportunities provided by stem cells and gene-editing
tools, and we provide insight into how the retinal therapeutic pipeline can be
improved. Finally, we discuss the current state of adeno-associated virus
mediated gene therapy and how it can be applied to treat retinopathies associated
with mutations in CRB1.
PMID- 28424580
TI - The Role of MicroRNA in the Modulation of the Melanocortinergic System.
AB - The central control of energy balance involves a highly regulated neuronal
network within the hypothalamus and the dorsal vagal complex. In these
structures, pro-opiomelanocortin (POMC) neurons are known to reduce meal size and
to increase energy expenditure. In addition, leptin, a peripheral signal that
relays information regarding body fat content, modulates the activity of
melanocortin pathway neurons including POMC-, Agouti-related peptide
(AgRP)/Neuropeptide Y (NPY)-, melanocortin receptors (MC3R and MC4R)-expressing
neurons. MicroRNAs (miRNAs) are short non-coding RNAs of 22-26 nucleotides that
post-transcriptionally interfere with target gene expression by binding to their
mRNAs. Evidence has demonstrated that miRNAs play important roles in the central
regulation of energy balance. In this context, different studies identified
miRNAs including miR-200 family, miR-103, or miR-488 that could target the genes
of melanocortin pathway. More precisely, these different miRNAs can modulate
energy homeostasis by affecting leptin transduction pathway in the POMC, or
AgRP/NPY neurons. This article reviews the role of identified miRNAs in the
modulation of melanocortin pathway in the context of energy homeostasis.
PMID- 28424579
TI - GRP78 at the Centre of the Stage in Cancer and Neuroprotection.
AB - The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a
multifunctional protein with activities far beyond its well-known role in the
unfolded protein response (UPR) which is activated after endoplasmic reticulum
(ER) stress in the cells. Most of these newly discovered activities depend on its
position within the cell. GRP78 is located mainly in the ER, but it has also been
observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane,
and secreted, although it is dedicated mostly to engage endogenous cytoprotective
processes. Hence, GRP78 may control either UPR and macroautophagy or may
activated phosphatidylinositol 3-kinase (PI3K)/AKT pro-survival pathways. GRP78
influences how tumor cells survive, proliferate, and develop chemoresistance. In
neurodegeneration, endogenous mechanisms of neuroprotection are frequently
insufficient or dysregulated. Lessons from tumor biology may give us clues about
how boosting endogenous neuroprotective mechanisms in age-related
neurodegeneration. Herein, the functions of GRP78 are revealed at the center of
the stage of apparently opposite sites of the same coin regarding cytoprotection:
neurodegeneration and cancer. The goal is to give a comprehensive and critical
review that may serve to guide future experiments to identify interventions that
will enhance neuroprotection.
PMID- 28424582
TI - Hypothalamic Neurogenesis as an Adaptive Metabolic Mechanism.
AB - In the adult brain, well-characterized neurogenic niches are located in the
subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone
(SGZ) of the hippocampus. In both regions, neural precursor cells (NPCs) share
markers of embryonic radial glia and astroglial cells, and in vitro clonal
expansion of these cells leads to neurosphere formation. It has also been more
recently demonstrated that neurogenesis occurs in the adult hypothalamus, a brain
structure that integrates peripheral signals to control energy balance and
dietary intake. The NPCs of this region, termed tanycytes, are ependymal-glial
cells, which comprise the walls of the infundibular recess of the third ventricle
and contact the median eminence. Thus, tanycytes are in a privileged position to
detect hormonal, nutritional and mitogenic signals. Recent studies reveal that in
response to nutritional signals, tanycytes are capable of differentiating into
orexigenic or anorexigenic neurons, suggesting that these cells are crucial for
control of feeding behavior. In this review, we discuss evidence, which suggests
that hypothalamic neurogenesis may act as an additional adaptive mechanism in
order to respond to changes in diet.
PMID- 28424581
TI - Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric
Neuroimaging.
AB - Type 2 diabetes mellitus is associated with accelerated cognitive decline and
various cerebral abnormalities visible on MRI. The exact pathophysiological
mechanisms underlying cognitive decline in diabetes still remain to be
elucidated. In addition to conventional images, MRI offers a versatile set of
novel contrasts, including blood perfusion, neuronal function, white matter
microstructure, and metabolic function. These more-advanced multiparametric MRI
contrasts and the pertaining parameters are able to reveal abnormalities in type
2 diabetes, which may be related to cognitive decline. To further elucidate the
nature of the link between diabetes, cognitive decline, and brain abnormalities,
and changes over time thereof, biomarkers are needed which can be provided by
advanced MRI techniques. This review summarizes to what extent MRI, especially
advanced multiparametric techniques, can elucidate the underlying neuronal
substrate that reflects the cognitive decline in type 2 diabetes.
PMID- 28424583
TI - A Rodent Model of Dynamic Facial Reanimation Using Functional Electrical
Stimulation.
AB - Facial paralysis can be a devastating condition, causing disfiguring facial
droop, slurred speech, eye dryness, scarring and blindness. This study
investigated the utility of closed-loop functional electric stimulation (FES) for
reanimating paralyzed facial muscles in a quantitative rodent model. The right
buccal and marginal mandibular branches of the rat facial nerve were transected
for selective, unilateral paralysis of whisker muscles. Microwire electrodes were
implanted bilaterally into the facial musculature for FES and electromyographic
(EMG) recording. With the rats awake and head-fixed, whisker trajectories were
tracked bilaterally with optical micrometers. First, the relationship between EMG
and volitional whisker movement was quantified on the intact side of the face.
Second, the effect of FES on whisker trajectories was quantified on the paralyzed
side. Third, closed-loop experiments were performed in which the EMG signal on
the intact side triggered FES on the paralyzed side to restore symmetric
whisking. The results demonstrate a novel in vivo platform for developing control
strategies for neuromuscular facial prostheses.
PMID- 28424584
TI - Hif-1alpha Overexpression Improves Transplanted Bone Mesenchymal Stem Cells
Survival in Rat MCAO Stroke Model.
AB - Bone mesenchymal stem cells (BMSCs) death after transplantation is a serious
obstacle impacting on the outcome of cell therapy for cerebral infarction. This
study was aimed to investigate whether modification of BMSCs with hypoxia
inducible factor 1alpha (Hif-1alpha) could enhance the survival of the implanted
BMSCs. BMSCs were isolated from Wistar rats, and were infected with Hif-1alpha
GFP lentiviral vector or Hif-1alpha siRNA. The modified BMSCs were exposed to
oxygen-glucose deprivation (OGD) condition, cellular viability and apoptosis were
then assessed. An inhibitor of AMPK (compound C) was used to detect whether AMPK
and mTOR were implicated in the functions of Hif-1alpha on BMSCs survival.
Besides, ultrastructure of BMSCs was observed and the expression of autophagy
markers was measured. The modified BMSCs were transplanted into middle cerebral
artery occlusion (MCAO) model of rats, and the cerebral infarction volume and
neurological function was assessed. The results indicated that Hif-1alpha
overexpression protected OGD induced injury by promoting cellular viability and
inhibiting apoptosis. AMPK was activated while mTOR was inactivated by Hif-1alpha
overexpression, and that might be through which Hif-1alpha functioned BMSCs
survival. Hif-1alpha overexpression promoted autophagy; more important, compound
C abolished the induction of Hif-1alpha on autophagy. Transplantation of the
overexpressed Hif-1alpha of BMSCs into the MCAO rats reduced brain infarct volume
and improved neurobehavioral outcome; besides, it inhibited pro-inflammatory
cytokines generation while promoted neurotrophin secretion. In conclusion, Hif
1alpha might be contributed in the survival of BMSCs by regulating the activation
of AMPK and mTOR, as well as by promoting autophagy.
PMID- 28424585
TI - Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after
Hair Cell Loss.
AB - Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of
cochlear hair cells and subsequent progressive degeneration of spiral ganglion
neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein
conserved from yeast to human, and knockout of Efr3a was reported to facilitate
the survival of hippocampal newborn neurons in adult mice. Previously, we found
Efr3a expression in the auditory neural pathway is upregulated soon after the
destruction of hair cells. Here we conducted a time-course analysis of drug
caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice
(Efr3a-/+, Efr3a KD) and their wild type littermates. Functional examination
showed that both groups of mice suffered from serious hearing loss with a higher
level of severity in wild type (WT) mice. Morphologic observation following drugs
administration showed that both WT and Efr3a KD mice went through progressive
loss of hair cells and SGNs, in association with degenerative changes in the
perikarya, intracellular organelles, cell body conformation in SGNs, and the
changes of SGNs in WT mice were more severe than in Efr3a KD mice. These
beneficial effects of Efr3a KD could be ascribed to an increase in the expression
of some neurotrophic factors and their receptors in Efr3a KD mice. Our results
indicate that Efr3a insufficiency suppresses drug-caused SNHL neurodegeneration
in association with an increase in the expression of some neurotrophic factors
and their receptors, which may be targeted in the treatment of neurodegeneration.
PMID- 28424587
TI - Interactions of the Mechanosensitive Channels with Extracellular Matrix,
Integrins, and Cytoskeletal Network in Osmosensation.
AB - Life is maintained in a sea water-like internal environment. The homeostasis of
this environment is dependent on osmosensory system translation of hydromineral
information into osmotic regulatory machinery at system, tissue and cell levels.
In the osmosensation, hydromineral information can be converted into cellular
reactions through osmoreceptors, which changes thirst and drinking, secretion of
antidiuretic vasopressin (VP), reabsorption of water and salt in the kidneys at
systemic level as well as cellular metabolic activity and survival status at
tissue level. The key feature of osmosensation is the activation of
mechanoreceptors or mechanosensors, particularly transient receptor potential
vallinoid (TRPV) and canonical (TRPC) family channels, which increases cytosolic
Ca2+ levels, activates osmosensory cells including VP neurons and triggers a
series of secondary reactions. TRPV channels are sensitive to both hyperosmotic
and hyposmotic stimuli while TRPC channels are more sensitive to hyposmotic
challenge in neurons. The activation of TRP channels relies on changes in cell
volume, membrane stretch and cytoskeletal reorganization as well as hydration
status of extracellular matrix (ECM) and activity of integrins. Different
families of TRP channels could be activated differently in response to
hyperosmotic and hyposmotic stimuli in different spatiotemporal orders, leading
to differential reactions of osmosensory cells. Together, they constitute the
osmosensory machinery. The activation of this osmoreceptor complex is also
associated with the activity of other osmolarity-regulating organelles, such as
water channel protein aquaporins, Na-K-2Cl cotransporters, volume-sensitive anion
channels, sodium pump and purinergic receptors in addition to intercellular
interactions, typically astrocytic neuronal interactions. In this article, we
review our current understandings of the composition of osmoreceptors and the
processes of osmosensation.
PMID- 28424586
TI - APP Protein Family Signaling at the Synapse: Insights from Intracellular APP
Binding Proteins.
AB - Understanding the molecular mechanisms underlying amyloid precursor protein
family (APP/APP-like proteins, APLP) function in the nervous system can be
achieved by studying the APP/APLP interactome. In this review article, we focused
on intracellular APP interacting proteins that bind the YENPTY internalization
motif located in the last 15 amino acids of the C-terminal region. These
proteins, which include X11/Munc-18-interacting proteins (Mints) and FE65/FE65Ls,
represent APP cytosolic binding partners exhibiting different neuronal functions.
A comparison of FE65 and APP family member mutant mice revealed a shared function
for APP/FE65 protein family members in neurogenesis and neuronal positioning.
Accumulating evidence also supports a role for membrane-associated APP/APLP
proteins in synapse formation and function. Therefore, it is tempting to
speculate that APP/APLP C-terminal interacting proteins transmit APP/APLP
dependent signals at the synapse. Herein, we compare our current knowledge of the
synaptic phenotypes of APP/APLP mutant mice with those of mice lacking different
APP/APLP interaction partners and discuss the possible downstream effects of APP
dependent FE65/FE65L or X11/Mint signaling on synaptic vesicle release, synaptic
morphology and function. Given that the role of X11/Mint proteins at the synapse
is well-established, we propose a model highlighting the role of FE65 protein
family members for transduction of APP/APLP physiological function at the
synapse.
PMID- 28424588
TI - Chaperones as Suppressors of Protein Misfolded Oligomer Toxicity.
AB - Chaperones have long been recognized to play well defined functions such as to:
(i) assist protein folding and promote formation and maintenance of multisubunit
complexes; (ii) mediate protein degradation; (iii) inhibit protein aggregation;
and (iv) promote disassembly of undesired aberrant protein aggregates. In
addition to these well-established functions, it is increasingly clear that
chaperones can also interact with aberrant protein aggregates, such as pre
fibrillar oligomers and fibrils, and inhibit their toxicity commonly associated
with neurodegenerative diseases without promoting their disassembly. In
particular, the evidence collected so far in different labs, exploiting different
experimental approaches and using different chaperones and client aggregated
proteins, indicates the existence of two distinct mechanisms of action mediated
by the chaperones to neutralize the toxicity of aberrant proteins oligomers: (i)
direct binding of the chaperones to the hydrophobic patches exposed on the
oligomer/fibril surface, with resulting shielding or masking of the moieties
responsible for the aberrant interactions with cellular targets; (ii) chaperone
mediated conversion of aberrant protein aggregates into large and more innocuous
species, resulting in a decrease of their surface-to-volume ratio and
diffusibility and in deposits more easily manageable by clearance mechanisms,
such as autophagy. In this review article we will describe the in vitro and in
vivo evidence supporting both mechanisms and how this results in a suppression of
the detrimental effects caused by protein misfolded aggregates.
PMID- 28424589
TI - The Calcium Channel C-Terminal and Synaptic Vesicle Tethering: Analysis by Immuno
Nanogold Localization.
AB - At chemical synapses the incoming action potential triggers the influx of Ca2+
through voltage-sensitive calcium channels (CaVs, typically CaV2.1 and 2.2) and
the ions binds to sensors associated with docked, transmitter filled synaptic
vesicles (SVs), triggering their fusion and discharge. The CaVs and docked SVs
are located within the active zone (AZ) region of the synapse which faces a
corresponding neurotransmitter receptor-rich region on the post-synaptic cell.
Evidence that the fusion of a SV can be gated by Ca2+ influx through a single CaV
suggests that the channel and docked vesicle are linked by one or more molecular
tethers (Stanley, 1993). Short and long fibrous SV-AZ linkers have been
identified in presynaptic terminals by electron microscopy and we recently imaged
these in cytosol-vacated synaptosome 'ghosts.' Using CaV fusion proteins combined
with blocking peptides we previously identified a SV binding site near the tip of
the CaV2.2 C-terminal suggesting that this intracellular channel domain
participates in SV tethering. In this study, we combined the synaptosome ghost
imaging method with immunogold labeling to localize CaV intracellular domains.
L45, raised against the C-terminal tip, tagged tethered SVs often as far as 100
nm from the AZ membrane whereas NmidC2, raised against a C-terminal mid-region
peptide, and C2Nt, raised against a peptide nearer the C-terminal origin,
resulted in gold particles that were proportionally closer to the AZ.
Interestingly, the observation of gold-tagged SVs with NmidC2 suggests a novel SV
binding site in the C-terminal mid region. Our results implicate the CaV C
terminal in SV tethering at the AZ with two possible functions: first, capturing
SVs from the nearby cytoplasm and second, contributing to the localization of the
SV close to the channel to permit single domain gating.
PMID- 28424590
TI - Geometrical Determinants of Neuronal Actin Waves.
AB - Hippocampal neurons produce in their early stages of growth propagative, actin
rich dynamical structures called actin waves. The directional motion of actin
waves from the soma to the tip of neuronal extensions has been associated with
net forward growth, and ultimately with the specification of neurites into axon
and dendrites. Here, geometrical cues are used to control actin wave dynamics by
constraining neurons on adhesive stripes of various widths. A key observable, the
average time between the production of consecutive actin waves, or mean inter
wave interval (IWI), was identified. It scales with the neurite width, and more
precisely with the width of the proximal segment close to the soma. In addition,
the IWI is independent of the total number of neurites. These two results suggest
a mechanistic model of actin wave production, by which the material conveyed by
actin waves is assembled in the soma until it reaches the threshold leading to
the initiation and propagation of a new actin wave. Based on these observations,
we formulate a predictive theoretical description of actin wave-driven neuronal
growth and polarization, which consistently accounts for different sets of
experiments.
PMID- 28424591
TI - Bcl11b-A Critical Neurodevelopmental Transcription Factor-Roles in Health and
Disease.
AB - B cell leukemia 11b (Bcl11b) is a zinc finger protein transcription factor with a
multiplicity of functions. It works as both a genetic suppressor and activator,
acting directly, attaching to promoter regions, as well as indirectly, attaching
to promoter-bound transcription factors. Bcl11b is a fundamental transcription
factor in fetal development, with important roles for the differentiation and
development of various neuronal subtypes in the central nervous system (CNS). It
has been used as a specific marker of layer V subcerebral projection neurons as
well as striatal interneurons. Bcl11b also has critical developmental functions
in the immune, integumentary and cardiac systems, to the extent that Bcl11b
knockout mice are incompatible with extra-uterine life. Bcl11b has been
implicated in a number of disease states including Huntington's disease,
Alzheimer's disease, HIV and T-Cell malignancy, amongst others. Bcl11b is a
fascinating protein whose critical roles in the CNS and other parts of the body
are yet to be fully explicated. This review summarizes the current literature on
Bcl11b and its functions in development, health, and disease as well as future
directions for research.
PMID- 28424593
TI - Phospholipase A2 of Peroxiredoxin 6 Plays a Critical Role in Cerebral
Ischemia/Reperfusion Inflammatory Injury.
AB - Microglia-mediated inflammation is an important step in the progression of
cerebral ischemia/reperfusion injury and the associated production of receptors
of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6
(Prdx6) has been demonstrated as the endogenous antioxidant protein for its
peroxidase properties. However, the role of the independent phospholipase A2
(iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we
evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and
inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33)
would have a critical effect on inflammatory brain damage. We conducted oxygen
glucose deprivation (OGD)/recovery (R) in vitro and middle cerebral artery
occlusion (MCAO) in vivo in a microglia/neuron co-culture system and in rats. In
vitro, we found that Prdx6-iPLA2 activity was associated with the secretion of
neurotoxic inflammatory mediators interleukin1beta (IL-1beta), interleukin-17 (IL
17) and interleukin-23 (IL-23) and elevated expression of Toll-like receptor 2/4
(TLR2/4), leading to the formation of nuclear factor-kappa B (NF-kappaB),
inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglial
cells. In vivo, combined treatment with Prdx6-iPLA2 activity inhibitor MJ33
showed a greater diminution in neurologic deficits, cerebral infarction, brain
water content and inflammatory molecules than Prdx6-siRNA treatment alone. Our
findings provide new insight into Prdx6-iPLA2 function in the brain. Inhibition
of Prdx6-iPLA2 activity by gene therapy and/or pharmacology may constitute a
promising new therapeutic approach to the treatment of stroke.
PMID- 28424594
TI - Overexpression of Human SOD1 Leads to Discrete Defects in the Cerebellar
Architecture in the Mouse.
AB - The human superoxide dismutase 1 (SOD1) gene is responsible for neutralizing
supercharged oxygen radicals within the cell. Mutation in SOD1 gene causes
amyotrophic lateral sclerosis (ALS). Recent studies have shown involvement of the
cerebellum in ALS, although the cerebellar contribution in SOD1 transgenic mice
remains unclear. Using immunohistopathology, we investigated the Purkinje cell
phenotype in the vermis of the SOD1 transgenic mice cerebellum. Calbindin 1
(Calb1) and three well-known zone and stripe markers, zebrin II, HSP25, and
PLCbeta4 have been used to explore possible alteration in zone and stripe. Here
we show that Calb1 expression is significantly reduced in a subset of the
Purkinje cells that is almost aligned with the cerebellar zones and stripes
pattern. The Purkinje cells of SOD1 transgenic mice display a pattern of Calb1
down-regulation, which seems to proceed to Purkinje cell degeneration as the mice
age. The onset of Calb1 down-regulation in Purkinje cells begins from the central
zone and continues into the nodular zone, however it has not been observed in the
anterior and posterior zones. In a subgroup of SOD1 transgenic mice in which gait
unsteadiness was apparent, down-regulation of Calb1 is seen in a subset of
PLCbeta4+ Purkinje cells in the anterior zone. These observations suggest that
the Calb1- subset of Purkinje cells in the anterior zone, which receives
somatosensory input, causes unsteady gait. Our data suggest that human SOD1
overexpression leads to Calb1 down-regulation in the zone and strip pattern and
raise the question of whether SOD1 overexpression leads to Purkinje cells
degeneration.
PMID- 28424595
TI - Gray Matter Atrophy Is Primarily Related to Demyelination of Lesions in Multiple
Sclerosis: A Diffusion Tensor Imaging MRI Study.
AB - Objective: Cortical pathology, periventricular demyelination, and lesion
formation in multiple sclerosis (MS) are related (Hypothesis 1). Factors in the
cerebrospinal fluid close to these compartments could possibly drive the parallel
processes. Alternatively, the cortical atrophy could be caused by remote axonal
transection (Hypothesis 2). Since MRI can differentiate between demyelination and
axon loss, we used this imaging modality to investigate the correlation between
the pattern of diffusion parameter changes in the periventricular- and deep white
matter and the gray matter atrophy. Methods: High-resolution T1-weighted, FLAIR,
and diffusion MRI images were acquired in 52 RRMS patients and 50 healthy, age
matched controls. We used EDSS to estimate the clinical disability. We used Tract
Based Spatial Statistics to compare diffusion parameters (fractional anisotropy,
mean, axial, and radial diffusivity) between groups. We evaluated global brain,
white, and gray matter atrophy with SIENAX. Averaged, standard diffusion
parameters were calculated in four compartment: periventricular lesioned and
normal appearing white matter, non-periventricular lesioned and normal appearing
white matter. PLS regression was used to identify which diffusion parameter and
in which compartment best predicts the brain atrophy and clinical disability.
Results: In our diffusion tensor imaging study compared to controls we found
extensive alterations of fractional anisotropy, mean and radial diffusivity and
smaller changes of axial diffusivity (maximal p > 0.0002) in patients that
suggested demyelination in the lesioned and in the normal appearing white matter.
We found significant reduction in total brain, total white, and gray matter
(patients: 718.764 +/- 14.968, 323.237 +/- 7.246, 395.527 +/- 8.050 cm3,
controls: 791.772 +/- 22.692, 355.350 +/- 10.929, 436.422 +/- 12.011 cm3; mean +/
SE), (p < 0.015; p < 0.0001; p < 0.009; respectively) of patients compared to
controls. The PLS analysis revealed a combination of demyelination-like diffusion
parameters (higher mean and radial diffusivity in patients) in the lesions and in
the non-lesioned periventricular white matter, which best predicted the gray
matter atrophy (p < 0.001). Similarly, EDSS was best predicted by the radial
diffusivity of the lesions and the non-lesioned periventricular white matter, but
axial diffusivity of the periventricular lesions also contributed significantly
(p < 0.0001). Interpretation: Our investigation showed that gray matter atrophy
and white matter demyelination are related in MS but white matter axonal loss
does not significantly contribute to the gray matter pathology.
PMID- 28424592
TI - New Implications for the Melanocortin System in Alcohol Drinking Behavior in
Adolescents: The Glial Dysfunction Hypothesis.
AB - Alcohol dependence causes physical, social, and moral harms and currently
represents an important public health concern. According to the World Health
Organization (WHO), alcoholism is the third leading cause of death worldwide,
after tobacco consumption and hypertension. Recent epidemiologic studies have
shown a growing trend in alcohol abuse among adolescents, characterized by the
consumption of large doses of alcohol over a short time period. Since brain
development is an ongoing process during adolescence, short- and long-term brain
damage associated with drinking behavior could lead to serious consequences for
health and wellbeing. Accumulating evidence indicates that alcohol impairs the
function of different components of the melanocortin system, a major player
involved in the consolidation of addictive behaviors during adolescence and
adulthood. Here, we hypothesize the possible implications of melanocortins and
glial cells in the onset and progression of alcohol addiction. In particular, we
propose that alcohol-induced decrease in alpha-MSH levels may trigger a cascade
of glial inflammatory pathways that culminate in altered gliotransmission in the
ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate
dopaminergic drive in the NAc, contributing to increase the vulnerability to
alcohol dependence and addiction in the adolescence and adulthood.
PMID- 28424596
TI - Non-Interfering Effects of Active Post-Encoding Tasks on Episodic Memory
Consolidation in Humans.
AB - So far, studies that investigated interference effects of post-learning processes
on episodic memory consolidation in humans have used tasks involving only complex
and meaningful information. Such tasks require reallocation of general or
encoding-specific resources away from consolidation-relevant activities. The
possibility that interference can be elicited using a task that heavily taxes our
limited brain resources, but has low semantic and hippocampal related long-term
memory processing demands, has never been tested. We address this question by
investigating whether consolidation could persist in parallel with an active,
encoding-irrelevant, minimally semantic task, regardless of its high resource
demands for cognitive processing. We distinguish the impact of such a task on
consolidation based on whether it engages resources that are: (1)
general/executive, or (2) specific/overlapping with the encoding modality. Our
experiments compared subsequent memory performance across two post-encoding
consolidation periods: quiet wakeful rest and a cognitively demanding n-Back
task. Across six different experiments (total N = 176), we carefully manipulated
the design of the n-Back task to target general or specific resources engaged in
the ongoing consolidation process. In contrast to previous studies that employed
interference tasks involving conceptual stimuli and complex processing demands,
we did not find any differences between n-Back and rest conditions on memory
performance at delayed test, using both recall and recognition tests. Our results
indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for
episodic memory consolidation; and (2) post-encoding cognitive engagement does
not interfere with memory consolidation when task-performance has minimal
semantic and hippocampally-based episodic memory processing demands. We discuss
our findings with reference to resource and reactivation-led interference
theories.
PMID- 28424598
TI - Editorial: Bridging the Theories of Affordances and Limb Apraxia.
PMID- 28424597
TI - Working Memory after Traumatic Brain Injury: The Neural Basis of Improved
Performance with Methylphenidate.
AB - Traumatic brain injury (TBI) often results in cognitive impairments for patients.
The aim of this proof of concept study was to establish the nature of
abnormalities, in terms of activity and connectivity, in the working memory
network of TBI patients and how these relate to compromised behavioral outcomes.
Further, this study examined the neural correlates of working memory improvement
following the administration of methylphenidate. We report behavioral, functional
and structural MRI data from a group of 15 Healthy Controls (HC) and a group of
15 TBI patients, acquired during the execution of the N-back task. The patients
were studied on two occasions after the administration of either placebo or 30 mg
of methylphenidate. Between group tests revealed a significant difference in
performance when HCs were compared to TBI patients on placebo [F(1, 28) = 4.426,
p < 0.05, eta p2 = 0.136]. This difference disappeared when the patients took
methylphenidate [F(1, 28) = 3.665, p = 0.66]. Patients in the middle range of
baseline performance demonstrated the most benefit from methylphenidate. Changes
in the TBI patient activation levels in the Left Cerebellum significantly and
positively correlated with changes in performance (r = 0.509, df = 13, p = 0.05).
Whole-brain connectivity analysis using the Left Cerebellum as a seed revealed
widespread negative interactions between the Left Cerebellum and parietal and
frontal cortices as well as subcortical areas. Neither the TBI group on
methylphenidate nor the HC group demonstrated any significant negative
interactions. Our findings indicate that (a) TBI significantly reduces the levels
of activation and connectivity strength between key areas of the working memory
network and (b) Methylphenidate improves the cognitive outcomes on a working
memory task. Therefore, we conclude that methylphenidate may render the working
memory network in a TBI group more consistent with that of an intact working
memory network.
PMID- 28424599
TI - Electrophysiological Sequelae of Hemispherotomy in Ipsilateral Human Cortex.
AB - Objectives: Hemispheric disconnection has been used as a treatment of medically
refractory epilepsy and evolved from anatomic hemispherectomy to functional
hemispherectomies to hemispherotomies. The hemispherotomy procedure involves
disconnection of an entire hemisphere with limited tissue resection and is
reserved for medically-refractory epilepsy due to diffuse hemispheric disease.
Although it is thought to be effective by preventing seizures from spreading to
the contralateral hemisphere, the electrophysiological effects of a
hemispherotomy on the ipsilateral hemisphere remain poorly defined. The objective
of this study was to evaluate the effects of hemispherotomy on the
electrophysiologic dynamics in peri-stroke and dysplastic cortex. Methods:
Intraoperative electrocorticography (ECoG) was recorded from ipsilateral cortex
in 5 human subjects with refractory epilepsy before and after hemispherotomy.
Power spectral density, mutual information, and phase-amplitude coupling were
measured from the ECoG signals. Results: Epilepsy was a result of remote
perinatal stroke in three of the subjects. In two of the subjects, seizures were
a consequence of dysplastic tissue: one with hemimegalencephaly and the second
with Rasmussen's encephalitis. Hemispherotomy reduced broad-band power spectral
density in peri-stroke cortex. Meanwhile, hemispherotomy increased power in the
low and high frequency bands for dysplastic cortex. Functional connectivity was
increased in lower frequency bands in peri-stroke tissue but not affected in
dysplastic tissue after hemispherotomy. Finally, hemispherotomy reduced band
specific phase-amplitude coupling in peristroke cortex but not dysplastic cortex.
Significance: Disconnecting deep subcortical connections to peri-stroke cortex
via a hemispherotomy attenuates power of oscillations and impairs the transfer of
information from large-scale distributed brain networks to the local cortex.
Hence, hemispherotomy reduces heterogeneity between neighboring cortex while
impairing phase-amplitude coupling. In contrast, dysfunctional networks in
dysplastic cortex lack the normal connectivity with distant networks. Therefore
hemispherotomy does not produce the same effects.
PMID- 28424601
TI - Editorial: Trends in Neuroergonomics.
PMID- 28424600
TI - Systems, Subjects, Sessions: To What Extent Do These Factors Influence EEG Data?
AB - Lab-based electroencephalography (EEG) techniques have matured over decades of
research and can produce high-quality scientific data. It is often assumed that
the specific choice of EEG system has limited impact on the data and does not add
variance to the results. However, many low cost and mobile EEG systems are now
available, and there is some doubt as to the how EEG data vary across these newer
systems. We sought to determine how variance across systems compares to variance
across subjects or repeated sessions. We tested four EEG systems: two standard
research-grade systems, one system designed for mobile use with dry electrodes,
and an affordable mobile system with a lower channel count. We recorded four
subjects three times with each of the four EEG systems. This setup allowed us to
assess the influence of all three factors on the variance of data. Subjects
performed a battery of six short standard EEG paradigms based on event-related
potentials (ERPs) and steady-state visually evoked potential (SSVEP). Results
demonstrated that subjects account for 32% of the variance, systems for 9% of the
variance, and repeated sessions for each subject-system combination for 1% of the
variance. In most lab-based EEG research, the number of subjects per study
typically ranges from 10 to 20, and error of uncertainty in estimates of the mean
(like ERP) will improve by the square root of the number of subjects. As a
result, the variance due to EEG system (9%) is of the same order of magnitude as
variance due to subjects (32%/sqrt(16) = 8%) with a pool of 16 subjects. The two
standard research-grade EEG systems had no significantly different means from
each other across all paradigms. However, the two other EEG systems demonstrated
different mean values from one or both of the two standard research-grade EEG
systems in at least half of the paradigms. In addition to providing specific
estimates of the variability across EEG systems, subjects, and repeated sessions,
we also propose a benchmark to evaluate new mobile EEG systems by means of ERP
responses.
PMID- 28424602
TI - Assessing the Driver's Current Level of Working Memory Load with High Density
Functional Near-infrared Spectroscopy: A Realistic Driving Simulator Study.
AB - Cognitive overload or underload results in a decrease in human performance which
may result in fatal incidents while driving. We envision that driver assistive
systems which adapt their functionality to the driver's cognitive state could be
a promising approach to reduce road accidents due to human errors. This research
attempts to predict variations of cognitive working memory load levels in a
natural driving scenario with multiple parallel tasks and to reveal predictive
brain areas. We used a modified version of the n-back task to induce five
different working memory load levels (from 0-back up to 4-back) forcing the
participants to continuously update, memorize, and recall the previous 'n' speed
sequences and adjust their speed accordingly while they drove for approximately
60 min on a highway with concurrent traffic in a virtual reality driving
simulator. We measured brain activation using multichannel whole head, high
density functional near-infrared spectroscopy (fNIRS) and predicted working
memory load level from the fNIRS data by combining multivariate lasso regression
and cross-validation. This allowed us to predict variations in working memory
load in a continuous time-resolved manner with mean Pearson correlations between
induced and predicted working memory load over 15 participants of 0.61 [standard
error (SE) 0.04] and a maximum of 0.8. Restricting the analysis to prefrontal
sensors placed over the forehead reduced the mean correlation to 0.38 (SE 0.04),
indicating additional information gained through whole head coverage. Moreover,
working memory load predictions derived from peripheral heart rate parameters
achieved much lower correlations (mean 0.21, SE 0.1). Importantly, whole head
fNIRS sampling revealed increasing brain activation in bilateral inferior frontal
and bilateral temporo-occipital brain areas with increasing working memory load
levels suggesting that these areas are specifically involved in workload-related
processing.
PMID- 28424603
TI - Commentary: Predictions and the brain: how musical sounds become rewarding.
PMID- 28424604
TI - Mapping Critical Language Sites in Children Performing Verb Generation: Whole
Brain Connectivity and Graph Theoretical Analysis in MEG.
AB - A classic left frontal-temporal brain network is known to support language
processes. However, the level of participation of constituent regions, and the
contribution of extra-canonical areas, is not fully understood; this is
particularly true in children, and in individuals who have experienced early
neurological insult. In the present work, we propose whole-brain connectivity and
graph-theoretical analysis of magnetoencephalography (MEG) source estimates to
provide robust maps of the pediatric expressive language network. We examined
neuromagnetic data from a group of typically-developing young children (n = 15,
ages 4-6 years) and adolescents (n = 14, 16-18 years) completing an auditory verb
generation task in MEG. All source analyses were carried out using a linearly
constrained minimum-variance (LCMV) beamformer. Conventional differential
analyses revealed significant (p < 0.05, corrected) low-beta (13-23 Hz) event
related desynchrony (ERD) focused in the left inferior frontal region (Broca's
area) in both groups, consistent with previous studies. Connectivity analyses
were carried out in broadband (3-30 Hz) on time-course estimates obtained at the
voxel level. Patterns of connectivity were characterized by phase locking value
(PLV), and network hubs identified through eigenvector centrality (EVC). Hub
analysis revealed the importance of left perisylvian sites, i.e., Broca's and
Wernicke's areas, across groups. The hemispheric distribution of frontal and
temporal lobe EVC values was asymmetrical in most subjects; left dominant EVC was
observed in 20% of young children, and 71% of adolescents. Interestingly, the
adolescent group demonstrated increased critical sites in the right cerebellum,
left inferior frontal gyrus (IFG) and left putamen. Here, we show that whole
brain connectivity and network analysis can be used to map critical language
sites in typical development; these methods may be useful for defining the
margins of eloquent tissue in neurosurgical candidates.
PMID- 28424605
TI - White Matter Integrity and Treatment-Based Change in Speech Performance in
Minimally Verbal Children with Autism Spectrum Disorder.
AB - We investigated the relationship between imaging variables for two
language/speech-motor tracts and speech fluency variables in 10 minimally verbal
(MV) children with autism. Specifically, we tested whether measures of white
matter integrity-fractional anisotropy (FA) of the arcuate fasciculus (AF) and
frontal aslant tract (FAT)-were related to change in percent syllable-initial
consonants correct, percent items responded to, and percent syllable insertion
errors (from best baseline to post 25 treatment sessions). Twenty-three MV
children with autism spectrum disorder (ASD) received Auditory-Motor Mapping
Training (AMMT), an intonation-based treatment to improve fluency in spoken
output, and we report on seven who received a matched control treatment. Ten of
the AMMT participants were able to undergo a magnetic resonance imaging study at
baseline; their performance on baseline speech production measures is compared to
that of the other two groups. No baseline differences were found between groups.
A canonical correlation analysis (CCA) relating FA values for left- and right
hemisphere AF and FAT to speech production measures showed that FA of the left AF
and right FAT were the largest contributors to the synthetic independent imaging
related variable. Change in percent syllable-initial consonants correct and
percent syllable-insertion errors were the largest contributors to the synthetic
dependent fluency-related variable. Regression analyses showed that FA values in
left AF significantly predicted change in percent syllable-initial consonants
correct, no FA variables significantly predicted change in percent items
responded to, and FA of right FAT significantly predicted change in percent
syllable-insertion errors. Results are consistent with previously identified
roles for the AF in mediating bidirectional mapping between articulation and
acoustics, and the FAT in its relationship to speech initiation and fluency. They
further suggest a division of labor between the hemispheres, implicating the left
hemisphere in accuracy of speech production and the right hemisphere in fluency
in this population. Changes in response rate are interpreted as stemming from
factors other than the integrity of these two fiber tracts. This study is the
first to document the existence of a subgroup of MV children who experience
increases in syllable- insertion errors as their speech develops in response to
therapy.
PMID- 28424606
TI - Bifurcation Analysis on Phase-Amplitude Cross-Frequency Coupling in Neural
Networks with Dynamic Synapses.
AB - We investigate a discrete-time network model composed of excitatory and
inhibitory neurons and dynamic synapses with the aim at revealing dynamical
properties behind oscillatory phenomena possibly related to brain functions. We
use a stochastic neural network model to derive the corresponding macroscopic
mean field dynamics, and subsequently analyze the dynamical properties of the
network. In addition to slow and fast oscillations arising from excitatory and
inhibitory networks, respectively, we show that the interaction between these two
networks generates phase-amplitude cross-frequency coupling (CFC), in which
multiple different frequency components coexist and the amplitude of the fast
oscillation is modulated by the phase of the slow oscillation. Furthermore, we
clarify the detailed properties of the oscillatory phenomena by applying the
bifurcation analysis to the mean field model, and accordingly show that the
intermittent and the continuous CFCs can be characterized by an aperiodic orbit
on a closed curve and one on a torus, respectively. These two CFC modes switch
depending on the coupling strength from the excitatory to inhibitory networks,
via the saddle-node cycle bifurcation of a one-dimensional torus in map (MT1SNC),
and may be associated with the function of multi-item representation. We believe
that the present model might have potential for studying possible functional
roles of phase-amplitude CFC in the cerebral cortex.
PMID- 28424607
TI - Multivariate Analysis of 18F-DMFP PET Data to Assist the Diagnosis of
Parkinsonism.
AB - An early and differential diagnosis of parkinsonian syndromes still remains a
challenge mainly due to the similarity of their symptoms during the onset of the
disease. Recently, 18F-Desmethoxyfallypride (DMFP) has been suggested to increase
the diagnostic precision as it is an effective radioligand that allows us to
analyze post-synaptic dopamine D2/3 receptors. Nevertheless, the analysis of
these data is still poorly covered and its use limited. In order to address this
challenge, this paper shows a novel model to automatically distinguish idiopathic
parkinsonism from non-idiopathic variants using DMFP data. The proposed method is
based on a multiple kernel support vector machine and uses the linear version of
this classifier to identify some regions of interest: the olfactory bulb,
thalamus, and supplementary motor area. We evaluated the proposed model for both,
the binary separation of idiopathic and non-idiopathic parkinsonism and the
multigroup separation of parkinsonian variants. These systems achieved accuracy
rates higher than 70%, outperforming DaTSCAN neuroimages for this purpose. In
addition, a system that combined DaTSCAN and DMFP data was assessed.
PMID- 28424608
TI - Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and
Iron Metabolism in Parkinson' Disease.
AB - Disrupted iron metabolism has been implicated in the pathogenesis of Parkinson's
disease (PD), a progressive neurodegenerative disorder that severely affects
movement and coordination, yet the molecular mechanisms underlying this
association remain unknown. To this end, we performed a transcriptomic meta
analysis of four blood microarrays in PD. We observed a significant
downregulation of genes related to hemoglobin including, hemoglobin delta (HBD),
alpha hemoglobin stabilizing protein (ASHP), genes implicated in iron metabolism
including, solute carrier family 11 member 2 (SLC11A2), ferrochelatase (FECH),
and erythrocyte-specific genes including erythrocyte membrane protein (EPB42),
and 5'-aminolevulinate synthase 2 (ALAS2). Pathway and network analysis
identified enrichment in processes related to mitochondrial membrane, oxygen
transport, oxygen and heme binding, hemoglobin complex, erythrocyte development,
tetrapyrrole metabolism and the spliceosome. Collectively, we identified a
subnetwork of genes in blood that may provide a molecular explanation for the
disrupted hemoglobin and iron metabolism in the pathogenesis of PD.
PMID- 28424609
TI - A Neurochemical Basis for Phenotypic Differentiation in Alzheimer's Disease?
Turing's Morphogens Revisited.
PMID- 28424610
TI - Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild
Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential
Biomarker.
AB - The presence and pattern of iron accumulation in subcortical vascular mild
cognitive impairment (svMCI) and their effects on cognition have rarely been
investigated. We aimed to examine brain iron deposition in svMCI subjects using
quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the
correlation between brain iron deposition and the severity of cognitive
impairment as indicated by z-scores. We recruited 20 subcortical ischemic
vascular disease (SIVD) patients who fulfilled the criteria for svMCI. The
control group comprised 19 SIVD patients without cognitive impairment. The SIVD
and control groups were matched based on age, gender, and years of education.
Both groups underwent QSM using a 3.0T MRI system. Susceptibility maps were
reconstructed from in vivo data, which were acquired with a three-dimensional
spoiled gradient recalled sequence. Then, regions of interest were drawn manually
on the map of each subject. The inter-group differences of susceptibility values
were explored in deep gray matter nuclei, including the bilateral pulvinar
nucleus of the thalamus, head of caudate nucleus, globus pallidus, putamen,
hippocampus, substantia nigra, and red nucleus. The correlations between regional
iron deposition and composite z-score, memory z-score, language z-score,
attention-executive z-score and visuospatial z-score were assessed using partial
correlation analysis, with patient age and gender as covariates. Compared with
the control, the svMCI group had elevated susceptibility values within the
bilateral hippocampus and right putamen. Furthermore, the susceptibility value in
the right hippocampus was negatively correlated with memory z-score and
positively correlated with language z-score. The susceptibility value in the
right putamen was negatively correlated with attention-executive z-score in the
svMCI group. However, composite z-score were unrelated to susceptibility values.
Our results suggest that brain iron deposition has clinical relevance as a
biomarker for cognition. In addition, our results highlight the importance of
iron deposition in understanding svMCI-associated cognitive deficits in addition
to conventional MRI markers.
PMID- 28424611
TI - Modafinil-Induced Changes in Functional Connectivity in the Cortex and Cerebellum
of Healthy Elderly Subjects.
AB - In the past few years, cognitive enhancing drugs (CEDs) have gained growing
interest and the focus of investigations aimed at exploring their use to
potentiate the cognitive performances of healthy individuals. Most of this
exploratory CED-related research has been performed on young adults. However,
CEDs may also help to maintain optimal brain functioning or compensate for subtle
and or subclinical deficits associated with brain aging or early-stage dementia.
In this study, we assessed effects on resting state brain activity in a group of
healthy elderly subjects undergoing acute administration of modafinil, a
wakefulness-promoting agent. To that aim, participants (n = 24) were investigated
with resting state functional Magnetic Resonance Imaging (rs-fMRI) before and
after the administration of a single dose (100 mg) of modafinil. Effects were
compared to age and size-matched placebo group. Rs-fMRI effects were assessed,
employing a graph-based approach and Eigenvector Centrality (EC) analysis, by
taking in account topological changes occurring in functional brain networks. The
main finding of the study is that modafinil promotes enhanced centrality, a
measure of the importance of nodes within functional networks, of the bilateral
primary visual (V1) cortex. EC analysis also revealed that modafinil-treated
subjects show increased functional connectivity between the V1 and specific
cerebellar (Crus I, Crus II, VIIIa lobule) and frontal (right inferior frontal
sulcus and left middle frontal gyrus) regions. Present findings provide
functional data supporting the hypothesis that modafinil can modulate the cortico
cerebellar connectivity of the aging brain.
PMID- 28424612
TI - An Examination of Brain Abnormalities and Mobility in Individuals with Mild
Cognitive Impairment and Alzheimer's Disease.
AB - Background: Mobility changes are concerning for elderly patients with cognitive
decline. Given frail older individuals' vulnerability to injury, it is critical
to identify contributors to limited mobility. Objective: To examine whether
structural brain abnormalities, including reduced gray matter volume and white
matter hyperintensities, would be associated with limited mobility among
individuals with cognitive impairment, and to determine whether cognitive
impairment would mediate this relationship. Methods: Thirty-four elderly
individuals with mild cognitive impairment (MCI) and Alzheimer's disease
underwent neuropsychological evaluation, mobility assessment, and structural
brain neuroimaging. Linear regression was conducted with predictors including
gray matter volume in six regions of interest (ROI) and white matter
hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower
gray matter volume in caudate nucleus was associated with slower speed on a
functional mobility task. Higher cerebellar volume was also associated with
slower functional mobility. White matter hyperintensity burden was not
significantly associated with mobility. Conclusion: Our findings provide evidence
for associations between subcortical gray matter volume and speed on a functional
mobility task among cognitively impaired individuals.
PMID- 28424613
TI - The Relationship between Cerebral Small Vessel Disease, Hippocampal Volume and
Cognitive Functioning in Patients with COPD: An MRI Study.
AB - The neural correlates of cognitive impairment in chronic obstructive pulmonary
disease (COPD) are not yet understood. Structural brain abnormalities could
possibly be associated with the presence of cognitive impairment through
cigarette smoke, inflammation, vascular disease, or hypoxemia in these patients.
This study aimed to investigate whether macrostructural brain magnetic resonance
imaging (MRI) features of cerebral small vessel disease (SVD) and hippocampal
volume (HCV) are related to cognitive performance in patients with COPD. A
subgroup of cognitively high and low-performing COPD patients of the COgnitive-PD
study, underwent a brain 3T MRI. SVD as a marker of vascular damage was assessed
using qualitative visual rating scales. HCV as a marker of neurodegeneration was
assessed using the learning embedding for atlas propagation (LEAP) method.
Features of SVD and HCV were compared between cognitively high and low-performing
individuals using Mann Whitney U tests and independent samples t-tests,
respectively. No group differences were reported between 25 high-performing (mean
age 60.3 (standard deviation [SD] 9.7) years; 40.0% men; forced expiratory volume
in first second [FEV1] 50.1% predicted) and 30 low-performing patients with COPD
(mean age 60.6 (SD 6.8) years; 53.3% men; FEV1 55.6% predicted) regarding
demographics, clinical characteristics, comorbidities and the presence of the SVD
features and HCV. To conclude, the current study does not provide evidence for a
relationship between cerebral SVD and HCV and cognitive functioning in patients
with COPD. Additional studies will be needed to determine other possible
mechanisms of cognitive impairment in patients with COPD, including
microstructural brain changes and inflammatory-, hormonal-, metabolic- and
(epi)genetic factors.
PMID- 28424614
TI - Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring
of Patients with Late-onset Alzheimer's Disease.
AB - Early neuropathological changes characteristic of late-onset Alzheimer's disease
(LOAD) involve brain stem and limbic structures that regulate neurovegetative
functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging
biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized
that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O
LOAD) would display a series of circadian rhythm abnormalities prior to the onset
of objective cognitive alterations. We tested 31 children of patients with LOAD
(O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease
(control subjects, CS) with basic tests of cognitive function, as well as
actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily
temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in
verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 +/-
0.4 vs. 8.6 +/- 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's
vocabulary 51.4 +/- 1.3 vs. 44.3 +/- 1.5, t = 2.49, df = 49, p < 0.001) compared
to CS, even though all participants had results within the clinically normal
range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 +/- 0.47 h
vs. 3.8 +/- 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O
LOAD was associated with a series of cardiac autonomic sleep-wake variables;
specifically indicators of greater sympathetic activity at night were related to
poorer cognition. The present results suggest sleep pattern deserves further
study as a potential neurobiological signature in LOAD, even in middle-aged, at
risk individuals.
PMID- 28424615
TI - HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by
Regulating Bile Acids Metabolism Homeostasis.
AB - Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical
usage is often limited by the induction of severe gastrointestinal (GI) toxicity,
especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the
treatment of GI ailments, has been proved could significantly ameliorate the
intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced
toxicity and the modulation effects of HQD, a previous untargeted metabolomics
study was performed and the results indicated that HQD may protect the GI tract
by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted
assays are often less sensitive and/or efficient. In order to further confirm our
previous findings, here in this paper, serum and tissues metabolic profiles of 17
BAs were analyzed using liquid chromatography-tandem mass spectrometry based
targeted metabolomics. The results indicated that serum and tissues levels of
most BAs were significantly decreased after CPT-11 administration, except some
hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI
toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that
the BAs pool size remained unchanged, the balance of BAs had shifted leading to
decreased toxicity after HQD treatment. The present study demonstrated for the
first time that the precise interaction between HQD, CPT-11-induced intestinal
toxicity and BAs' homeostasis.
PMID- 28424616
TI - Whole Blood Cytokine Response to Local Traffic-Related Particulate Matter in
Peruvian Children With and Without Asthma.
AB - This study sought to investigate if acute phase immune responses of whole blood
from Peruvian children with controlled and uncontrolled asthma differed from
children without asthma, following exposure to traffic-related particulate matter
(TRPM). TRPM, including particulate matter from diesel combustion, has been shown
to stimulate acute airway inflammation in individuals with and without asthma.
For this study, a whole blood assay (WBA) was used to test peripheral whole blood
samples from 27 children with asthma, and 12 without asthma. Participant blood
samples were stimulated, ex vivo, for 24-h with an aqueous extract of TRPM that
was collected near study area highways in Lima, Peru. All participant blood
samples were tested against the same TRPM extract, in addition to purified
bacterial endotoxin and pyrogen-free water, which served as positive and negative
WBA controls, respectively. The innate and adaptive cytokine responses were
evaluated in cell-free supernatants of the whole blood incubations. Comparatively
similar levels were recorded for nine out of the 10 cytokines measured [e.g., -
Interleukin (IL)-1beta, IL-6, IL-10], regardless of study participant asthma
status. However, IL-8 levels in TRPM-stimulated blood from children with
uncontrolled asthma were diminished, compared to subjects without asthma (633
pg/ml vs. 1,023 pg/ml, respectively; p < 0.01); IL-8 responses for subjects with
controlled asthma were also reduced, but to a lesser degree (799 pg/ml vs. 1,023
pg/ml, respectively; p = 0.10). These relationships were present before, and
after, adjusting for age, sex, obesity/overweight status, C-reactive protein
levels, and residential proximity to the study area's major roadway. For tests
conducted with endotoxin, there were no discernible differences in cytokine
response between groups, for all cytokines measured. The WBA testing conducted
for this study highlighted the capacity of the TRPM extract to potently elicit
the release of IL-8 from the human whole blood system. Although the small sample
size of the study limits the capacity to draw definitive conclusions, the IL-8
responses suggest that that asthma control may be associated with the regulation
of a key mediator in neutrophil chemotaxis, at a systemic level, following
exposure to PM derived from traffic-related sources.
PMID- 28424617
TI - Targeting Bile Acid Receptors: Discovery of a Potent and Selective Farnesoid X
Receptor Agonist as a New Lead in the Pharmacological Approach to Liver Diseases.
AB - Bile acid (BA) receptors represent well-defined targets for the development of
novel therapeutic approaches to metabolic and inflammatory diseases. In the
present study, we report the generation of novel C-3 modified 6-ethylcholane
derivatives. The pharmacological characterization and molecular docking studies
for the structure-activity rationalization, allowed the identification of 3beta
azido-6alpha-ethyl-7alpha-hydroxy-5beta-cholan-24-oic acid (compound 2), a potent
and selective FXR agonist with a nanomolar potency in transactivation assay and
high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen
assay. In vitro, compound 2 was completely inactive towards common off-targets
such as the nuclear receptors PPARalpha, PPARgamma, LXRalpha, and LXRbeta and the
membrane G-coupled BA receptor, GPBAR1. This compound when administered in vivo
exerts a robust FXR agonistic activity increasing the liver expression of FXR
target genes including SHP, BSEP, OSTalpha, and FGF21, while represses the
expression of CYP7A1 gene that is negatively regulated by FXR. Collectively these
effects result in a significant reshaping of BA pool in mouse. In summary,
compound 2 represents a promising candidate for drug development in liver and
metabolic disorders.
PMID- 28424618
TI - Pharmacological and Biochemical Characterization of TLQP-21 Activation of a
Binding Site on CHO Cells.
AB - VGF is a propeptide of 617 amino acids expressed throughout the central and the
peripheral nervous system. VGF and peptides derived from its processing have been
found in dense core vesicles and are released from neuronal and neuroendocrine
cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP
21 (VGF556-576) has raised a huge interest and is one of most studied. TLQP-21 is
a multifunctional neuropeptide involved in the control of several physiological
functions, potentially including energy homeostasis, pain modulation, stress
responsiveness and reproduction. Although little information is available about
its receptor and the intracellular mechanisms mediating its biological effects,
recent reports suggest that TLQP-21 may bind to the complement receptors C3aR1
and/or gC1qR. The first aim of this study was to ascertain the existence and
nature of TLQP-21 binding sites in CHO cells. Secondly, we endeavored to
characterize the ligand binding to these sites by using a small panel of VGF
derived peptides. And finally, we investigated the influence of TLQP-21 on
selected intracellular signaling pathways. We report that CHO cells express a
single class of saturable and specific binding sites for TLQP-21 with an affinity
and capacity of Kd = 0.55 +/- 0.05 * 10-9 M and Bmax = 81.7 +/- 3.9 fmol/mg
protein, respectively. Among the many bioactive products derived from the C
terminal region of VGF that we tested, TLQP-21 was the most potent in stimulating
intracellular calcium mobilization in CHO cells; this effect is primarily due to
its C-terminal fragment (HFHH-10). TLQP-21 induced rapid and transient
dephosphorylation of phospholipase Cgamma1 and phospholipase A2. Generation of
IP3 and diacylglycerol was crucial for TLQP-21 bioactivity. In conclusion, our
results suggest that the receptor stimulated by TLQP-21 belongs to the family of
the Gq-coupled receptors, and its activation first increases membrane-lipid
derived second messengers which thereby induce the mobilization of Ca2+ from the
endoplasmic reticulum followed by a slower store-operated Ca2+ entry from outside
the cell.
PMID- 28424620
TI - Relations between Effects and Structure of Small Bicyclic Molecules on the
Complex Model System Saccharomyces cerevisiae.
AB - The development of compounds able to modify biological functions largely took
advantage of parallel synthesis to generate a broad chemical variance of
compounds to be tested for the desired effect(s). The budding yeast Saccharomyces
cerevisiae is a model for pharmacological studies since a long time as it
represents a relatively simple system to explore the relations among chemical
variance and bioactivity. To identify relations between the chemical features of
the molecules and their activity, we delved into the effects of a library of
small compounds on the viability of a set of S. cerevisiae strains. Thanks to the
high degree of chemical diversity of the tested compounds and to the measured
effect on the yeast growth rate, we were able to scale-down the chemical library
and to gain information on the most effective structures at the substituent
level. Our results represent a valuable source for the selection, rational
design, and optimization of bioactive compounds.
PMID- 28424619
TI - Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo
Animal and Human Study.
AB - Age related macular degeneration (AMD) is the leading cause of blindness among
people aged 50 and over. Retinal deposition of amyloid-beta (Abeta) aggregates in
AMD patients has suggested a potential link between AMD and Alzheimer's disease
(AD). We have evaluated the differential retinal expression profile of miRNAs in
a rat model of AMD elicited by Abeta. A serum profile of miRNAs in AMD patients
has been also assessed using single TaqMan assay. Analysis of retina from rats
intravitreally injected with Abeta revealed that miR-27a, miR-146a, and miR-155
were up-regulated in comparison to control rats. Seven miRNA (miR-9, miR-23a, miR
27a, miR-34a, miR-126, miR-146a, and miR-155) have been found to be dysregulated
in serum of AMD patients in comparison to control group. Analysis of pathways has
revealed that dysregulated miRNAs, both in the AMD animal model and in AMD
patients, can target genes regulating pathways linked to neurodegeneration and
inflammation, reinforcing the hypothesis that AMD is a protein misfolding disease
similar to AD. In fact, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have
been found to be dysregulated both in AMD and AD. In conclusion, we suggest that
miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 represent potential
biomarkers and new pharmacological targets for AMD.
PMID- 28424621
TI - Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in
Cisplatin-induced Acute Kidney Injury.
AB - Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle
(Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and
antitumor properties. Here, we showed that silybin protected against cisplatin
induced acute kidney injury (AKI) by improving mitochondrial function through the
regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO)
mice were administered a single intraperitoneal (i.p.) injection of cisplatin
with or without treatment with silybin. Moreover, cultured HK2 cells were used to
evaluate mitochondrial morphology and function. Our data suggested that silybin
enhanced SIRT3 expression after cisplatin administration both in vivo and in
vitro. Silybin treatment improved mitochondrial function and bioenergetics in
wild-type, but not SIRT3-defective, cells and mice. Moreover, we demonstrated
that silybin markedly attenuated cisplatin-induced AKI and tubular cell apoptosis
and improved cell regeneration in a SIRT3-dependent manner. Collectively, these
results suggest that silybin is a pharmacological activator of SIRT3 capable of
protecting against cisplatin-induced tubular cell apoptosis and AKI by improving
mitochondrial function. Thus, silybin could serve as a potential clinical
renoprotective adjuvant treatment in cisplatin chemotherapy.
PMID- 28424622
TI - Pravastatin Chronic Treatment Sensitizes Hypercholesterolemic Mice Muscle to
Mitochondrial Permeability Transition: Protection by Creatine or Coenzyme Q10.
AB - Statins are efficient cholesterol-lowering medicines utilized worldwide. However,
10% of patients suffer from adverse effects specially related to skeletal muscle
function. Pro- or anti-oxidant effects of statins have been reported. Here we
hypothesized that statins induce muscle mitochondrial oxidative stress leading to
mitochondrial permeability transition (MPT) which may explain statin muscle
toxicity. Thus, our aims were to investigate the effects of statin chronic
treatment on muscle mitochondrial respiration rates, MPT and redox state
indicators in the context of hypercholesterolemia. For this purpose, we studied
muscle biopsies of the hypercholesterolemic LDL receptor knockout mice (LDLr-/-)
treated with pravastatin during 3 months. Plantaris, but not soleus muscle of
treated mice showed significant inhibition of respiration rates induced by ADP (
14%), oligomycin (-20%) or FCCP (-40%). Inhibitions of respiratory rates were
sensitive to EGTA (Ca2+ chelator), cyclosporin A (MPT inhibitor), ruthenium red
(inhibitor of mitochondria Ca2+ uptake) and coenzyme Q10 (antioxidant),
indicating that pravastatin treatment favors Ca2+ induced MPT. Diet
supplementation with creatine (antioxidant) also protected treated mice against
pravastatin sensitization to Ca2+ induced MPT. Among several antioxidant enzymes
analyzed, only catalase activity was increased by 30% in plantaris muscle of
pravastatin treated mice. Oxidized lipids, but not proteins biomarkers were
identified in treated LDLr-/- plantaris muscle. Taken together, the present
results suggest that chronic pravastatin administration to a model of familial
hypercholesterolemia promotes mitochondrial dysfunctions in plantaris muscle that
can be counteracted by antioxidants administered either in vitro (CoQ10) or in
vivo (creatine). Therefore, we propose that inhibition of muscle mitochondrial
respiration by pravastatin leads to an oxidative stress that, in the presence of
calcium, opens the permeability transition pore. This mitochondrial oxidative
stress caused by statin treatment also signals for cellular antioxidant system
responses such as catalase upregulation. These results suggest that the
detrimental effects of statins on muscle mitochondria could be prevented by co
administration of a safe antioxidant such as creatine or CoQ10.
PMID- 28424623
TI - Notch Signaling in Ischemic Damage and Fibrosis: Evidence and Clues from the
Heart.
AB - Notch signaling is a major intercellular coordination mechanism highly conserved
throughout evolution. In vertebrates, Notch signaling is physiologically involved
in embryo development, including mesenchymal cell commitment, formation of heart
tissues and angiogenesis. In post-natal life, Notch signaling is maintained as a
key mechanism of cell-cell communication and its dysregulations have been found
in pathological conditions such as ischemic and fibrotic diseases. In the heart,
Notch takes part in the protective response to ischemia, being involved in pre-
and post-conditioning, reduction of reperfusion-induced oxidative stress and
myocardial damage, and cardiomyogenesis. Conceivably, the cardioprotective
effects of Notch may depend on neo-angiogenesis, thus blunting lethal myocardial
ischemia, as well as on direct stimulation of cardiac cells to increase their
resistance to injury. Another post-developmental adaptation of Notch signaling is
fibrosis: being involved in the orientation of mesenchymal cell fate, Notch can
modulate the differentiation of pro-fibrotic myofibroblasts, e.g., by reducing
the effects of the profibrotic cytokine TGF-beta. In conclusion, Notch can
regulate the interactions between heart muscle and stromal cells and switch
cardiac repair from a pro-fibrotic default pathway to a pro-cardiogenic one.
These features make Notch signaling a suitable target for new cardiotropic
therapies.
PMID- 28424624
TI - Commentary: A BK (Slo1) channel journey from molecule to physiology.
PMID- 28424626
TI - A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model
for Bed Rest?
AB - Bed rest has been an established treatment in the past prescribed for critically
illness or convalescing patients, in order to preserve their body metabolic
resource, to prevent serious complications and to support their rapid path to
recovery. However, it has been reported that prolonged bed rest can have
detrimental consequences that may delay or prevent the recovery from clinical
illness. In order to study disuse-induced changes in muscle and bone, as observed
during prolonged bed rest in humans, an innovative new model of muscle disuse for
rodents is presented. Basically, the animals are confined to a reduced space
designed to restrict their locomotion movements and allow them to drink and eat
easily, without generating physical stress. The animals were immobilized for
either 7, 14, or 28 days. The immobilization procedure induced a significant
decrease of food intake, both at 14 and 28 days of immobilization. The reduced
food intake was not a consequence of a stress condition induced by the model
since plasma corticosterone levels -an indicator of a stress response- were not
altered following the immobilization period. The animals showed a significant
decrease in soleus muscle mass, grip force and cross-sectional area (a measure of
fiber size), together with a decrease in bone mineral density. The present model
may potentially serve to investigate the effects of bed-rest in pathological
states characterized by a catabolic condition, such as diabetes or cancer.
PMID- 28424627
TI - Blood Pressure Increase during Oxygen Supplementation in Chronic Kidney Disease
Patients Is Mediated by Vasoconstriction Independent of Baroreflex Function.
AB - Renal hypoxia is thought to be an important pathophysiological factor in the
progression of chronic kidney disease (CKD) and the associated hypertension. In a
previous study among CKD patients, supplementation with 100% oxygen reduced
sympathetic nerve activity (SNA) and lowered blood pressure (BP). We aimed to
assess the underlying haemodynamic modulation and hypothesized a decreased
systemic vascular resistance (SVR). To that end, 19 CKD patients were studied
during 15-min intervals of increasing partial oxygen pressure (ppO2) from room
air (0.21 ATA) to 1.0 ATA and further up to 2.4 ATA, while continuously measuring
finger arterial blood pressure (Finapres). Off-line, we derived indexes of SVR,
cardiac output (CO) and baroreflex sensitivity from the continuous BP recordings
(Modelflow). During oxygen supplementation, systolic, and diastolic BP both
increased dose-dependently from 128 +/- 24 and 72 +/- 19 mmHg respectively at
baseline to 141 +/- 23 (p < 0.001) and 80 +/- 21 mmHg (p < 0.001) at 1.0 ATA
oxygen. Comparing baseline and 1.0 ATA oxygen, SVR increased from 1440 +/- 546 to
1745 +/- 710 dyn.s/cm5 (p = 0.009), heart rate decreased from 60 +/- 8 to 58 +/-
6 bpm (p < 0.001) and CO from 5.0 +/- 1.3 to 4.6 +/- 1.1 L/min (p = 0.02).
Baroreflex sensitivity remained unchanged (13 +/- 13 to 15 +/- 12 ms/mmHg). These
blood pressure effects were absent in a negative control group of eight young
healthy subjects. We conclude that oxygen supplementation in CKD patients causes
a non-baroreflex mediated increased in SVR and blood pressure.
PMID- 28424625
TI - Role of Mitochondrial Retrograde Pathway in Regulating Ethanol-Inducible
Filamentous Growth in Yeast.
AB - In yeast, ethanol is produced as a by-product of fermentation through glycolysis.
Ethanol also stimulates a developmental foraging response called filamentous
growth and is thought to act as a quorum-sensing molecule. Ethanol-inducible
filamentous growth was examined in a small collection of wine/European strains,
which validated ethanol as an inducer of filamentous growth. Wine strains also
showed variability in their filamentation responses, which illustrates the
striking phenotypic differences that can occur among individuals. Ethanol
inducible filamentous growth in Sigma1278b strains was independent of several of
the major filamentation regulatory pathways [including fMAPK, RAS-cAMP, Snf1,
Rpd3(L), and Rim101] but required the mitochondrial retrograde (RTG) pathway, an
inter-organellar signaling pathway that controls the nuclear response to defects
in mitochondrial function. The RTG pathway regulated ethanol-dependent
filamentous growth by maintaining flux through the TCA cycle. The ethanol
dependent invasive growth response required the polarisome and transcriptional
induction of the cell adhesion molecule Flo11p. Our results validate established
stimuli that trigger filamentous growth and show how stimuli can trigger highly
specific responses among individuals. Our results also connect an inter
organellar pathway to a quorum sensing response in fungi.
PMID- 28424628
TI - Branchial Pathomorphology of Southern Bluefin Tuna Thunnus maccoyii (Castelnau,
1872) Infected by Helminth and Copepodan Parasites.
AB - Three metazoan parasites, a monogenean Hexostoma thynni and two species of
copepods Pseudocycnus appendiculatus and Euryphorus brachypterus are known to
parasitize the gills of ranched southern bluefin tuna (SBT) and other tuna
species. However, there is no detailed information describing the pathological
response to infection by these parasites in this species. Wild southern bluefin
tuna Thunnus maccoyii (approximately 3 years of age), captured and towed to a
grow-out site in the waters immediately south of Port Lincoln, South Australia
were subsequently sampled (n = 10) monthly from March until August 2004 during
commercial harvest operations. Longitudinal sections of gill hemibranchs with
attached parasites were excised and fixed for routine histology and
immunohistochemistry. Reference samples were also collected from fish displaying
no signs of parasitism or other grossly observable anomalies. Two morphologically
distinct granulocytes were observed and putatively identified as eosinophils and
mast cells. Pathology was localized to filaments upon and immediately adjacent to
parasite attachment sites. Branchial cellular responses, adjunct to the
attachment of H. thynni by its opisthaptoral clamps, included hyperplasia and
inflammation resulting in structural remodeling of branchial tissues.
Inflammatory infiltrates were often dominated by putative eosinophils and
lymphocytes when parasitized by H. thynni and P. appendiculatus. Gill associated
lymphoid tissue infiltrated the lamellar regions particularly in response to
helminth infection. A variable response ranging from hemorrhage with minor
hyperplasia or fibroplasia and eosinophilic inflammation to a barely discernible
change was seen for gill sections harboring P. appendiculatus and E.
brachypterus. The magnitude of the host response to attachment by the latter was
congruent with attachment proximity and parasite load. On the basis of the host
responses reported here and the low intensity of infection observed in other
associated studies these gill ectoparasites are currently considered a low risk
for wild and ranched adult SBT.
PMID- 28424630
TI - Hippo Pathway and Skeletal Muscle Mass Regulation in Mammals: A Controversial
Relationship.
AB - Skeletal muscle mass reflects a dynamic turnover between net protein synthesis
and degradation. In addition, satellite cell inclusion may contribute to increase
muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a
few studies looked at the involvement of the newly discovered Hippo pathway in
the regulation of muscle mass. In line with its roles in other organs, it has
been hypothesized that the Hippo pathway could play a role in different
regulatory mechanisms in skeletal muscle as well, namely proliferation and
renewal of satellite cells, differentiation, death, and growth of myogenic cells.
While the Hippo components have been identified in skeletal muscle, their role in
muscle mass regulation has been less investigated and conflicting results have
been reported. Indeed, the first studies described both atrophic and hypertrophic
roles of the Hippo pathway and its effectors Yap/Taz using different biochemical
approaches. Further, investigation is therefore warranted to determine the role
of the Hippo pathway in the regulation of skeletal muscle mass. New components of
the pathway will probably emerge and unsuspected roles will likely be discovered
due to its numerous interactions with different cellular processes. This mini
review aims to summarize the current literature concerning the roles of the Hippo
pathway in the regulation of muscle mass and to develop the hypothesis that this
pathway could contribute to muscle mass adaptation after exercise.
PMID- 28424629
TI - Molecular and Cellular Mechanisms of Apoptosis during Dissociated
Spermatogenesis.
AB - Apoptosis is a tightly controlled process by which tissues eliminate unwanted
cells. Spontaneous germ cell apoptosis in testis has been broadly investigated in
mammals that have an associated spermatogenesis pattern. However, the mechanism
of germ cell apoptosis in seasonally breeding reptiles following a dissociated
spermatogenesis has remained enigmatic. In the present study, morphological
evidence has clearly confirmed the dissociated spermatogenesis pattern in
Pelodiscus sinensis. TUNEL and TEM analyses presented dynamic changes and
ultrastructural characteristics of apoptotic germ cells during seasonal
spermatogenesis, implying that apoptosis might be one of the key mechanisms to
clear degraded germ cells. Furthermore, using RNA-Seq and digital gene expression
(DGE) profiling, a large number of apoptosis-related differentially expressed
genes (DEGs) at different phases of spermatogenesis were identified and
characterized in the testis. DGE and RT-qPCR analysis revealed that the critical
anti-apoptosis genes, such as Bcl-2, BAG1, and BAG5, showed up-regulated patterns
during intermediate and late spermatogenesis. Moreover, the increases in
mitochondrial transmembrane potential in July and October were detected by JC-1
staining. Notably, the low protein levels of pro-apoptotic cleaved caspase-3 and
CytC in cytoplasm were detected by immunohistochemistry and western blot
analyses, indicating that the CytC-Caspase model might be responsible for the
effects of germ cell apoptosis on seasonal spermatogenesis. These results
facilitate understanding the regulatory mechanisms of apoptosis during
spermatogenesis and uncovering the biological process of the dissociated
spermatogenesis system in reptiles.
PMID- 28424631
TI - Mechanisms Underlying the Emergence of Post-acidosis Arrhythmia at the Tissue
Level: A Theoretical Study.
AB - Acidosis has complex electrophysiological effects, which are associated with a
high recurrence of ventricular arrhythmias. Through multi-scale cardiac computer
modeling, this study investigated the mechanisms underlying the emergence of post
acidosis arrhythmia at the tissue level. In simulations, ten Tusscher-Panfilov
ventricular model was modified to incorporate various data on acidosis-induced
alterations of cellular electrophysiology and intercellular electrical coupling.
The single cell models were incorporated into multicellular one-dimensional (1D)
fiber and 2D sheet tissue models. Electrophysiological effects were quantified as
changes of action potential profile, sink-source interactions of fiber tissue,
and the vulnerability of tissue to the genesis of unidirectional conduction that
led to initiation of re-entry. It was shown that acidosis-induced sarcoplasmic
reticulum (SR) calcium load contributed to delayed afterdepolarizations (DADs) in
single cells. These DADs may be synchronized to overcome the source-sink mismatch
arising from intercellular electrotonic coupling, and produce a premature
ventricular complex (PVC) at the tissue level. The PVC conduction can be
unidirectionally blocked in the transmural ventricular wall with altered
electrical heterogeneity, resulting in the genesis of re-entry. In conclusion,
altered source-sink interactions and electrical heterogeneity due to acidosis
induced cellular electrophysiological alterations may increase susceptibility to
post-acidosis ventricular arrhythmias.
PMID- 28424632
TI - Pro-angiogenic Role of Insulin: From Physiology to Pathology.
AB - The underlying molecular mechanisms involve in the regulation of the angiogenic
process by insulin are not well understood. In this review article, we aim to
describe the role of insulin and insulin receptor activation on the control of
angiogenesis and how these mechanisms can be deregulated in human diseases.
Functional expression of insulin receptors and their signaling pathways has been
described on endothelial cells and pericytes, both of the main cells involved in
vessel formation and maturation. Consequently, insulin has been shown to regulate
endothelial cell migration, proliferation, and in vitro tubular structure
formation through binding to its receptors and activation of intracellular
phosphorylation cascades. Furthermore, insulin-mediated pro-angiogenic state is
potentiated by generation of vascular growth factors, such as the vascular
endothelial growth factor, produced by endothelial cells. Additionally, diseases
such as insulin resistance, obesity, diabetes, and cancer may be associated with
the deregulation of insulin-mediated angiogenesis. Despite this knowledge, the
underlying molecular mechanisms need to be elucidated in order to provide new
insights into the role of insulin on angiogenesis.
PMID- 28424633
TI - Psychopathological Aspects in Childhood Hematopoietic Stem Cell Transplantation
(HSCT): The Perception of Parents and Adolescents.
AB - Background: Data about psychosocial sequelae of childhood Hematopoietic Stem Cell
Transplantation (HSCT) are limited and the association with a specific donor type
or other medical factors is largely unknown (Chang et al., 2012). The aim of the
present study was to compare the psychological aspects of pediatric HSCT
survivors with healthy peers. A secondary aim was to detect whether parents and
children differed in the perception of mental health status. The influence of
medical factors on psychological status was also examined. Method: Thirty seven
HSCT survivors (23 males) with a mean age of 14.4 years (SD = 3.03; range 8.16
18.33) were recruited. Twenty-six patients underwent an allogenic HSCT (matched
unrelated donor, n = 20; matched sibling donor, n = 6) and 11 patients received
an autologous HSCT. The children psychological aspects were assessed using the
Youth Self Report (YSR) (Achenbach and Rescorla, 2001) and compared to a group of
matched healthy peers. At the same time, parents were requested to complete the
Child Behavior Checklist 6-18 (Achenbach and Rescorla, 2001). Medical and socio
demographic data were also collected. Results: HSCT survivors reported
significantly higher levels of somatic complains (t27 = 3.14; p = 0.004; mean =
3.1) when compared to healthy peers (mean = 1.5). The parent CBCL scores on
"child total competence" exceeded the normative clinical cutoff in 48.6% cases.
Inter-rater agreement between parent and patient reports was present only in
three scales: total competence score (K = 0.06, p = 0.002), somatic complaints (K
= 0.21, p = 0.003) and attention problems (k = 0.13; p = 0.02). According to
Ancova models, internalizing problems were more frequent in HSCT from family
donors (F2 = 3.13; p = 0.06) or in the presence of acute complications (F1 =
11.95; p = 0.003). Conclusion: In contrast to the perception of parents,
pediatric HSCT survivors reported good psychological health. However, they
complained about more somatic problems as compared with healthy peers. Medical
aspects such as donor source and the presence of acute complications should be
taken into consideration for the psychological approach in order to improve
pediatric HSCT survivor care.
PMID- 28424634
TI - When the Second Language Takes the Lead: Neurocognitive Processing Changes in the
First Language of Adult Attriters.
AB - Although research on multilingualism has revealed continued neuroplasticity for
language-learning beyond what was previously expected, it remains controversial
whether and to what extent a second language (L2) acquired in adulthood may
induce changes in the neurocognitive processing of a first language (L1). First
language (L1) attrition in adulthood offers new insight on neuroplasticity and
the factors that modulate neurocognitive responses to language. To date,
investigations of the neurocognitive correlates of L1 attrition and of factors
influencing these mechanisms are still scarce. Moreover, most event-related
potential (ERP) studies of second language processing have focused on L1
influence on the L2, while cross-linguistic influence in the reverse direction
has been underexplored. Using ERPs, we examined the real-time processing of
Italian relative-clauses in 24 Italian-English adult migrants with predominant
use of English since immigration and reporting attrition of their native-Italian
(Attriters), compared to 30 non-attriting monolinguals in Italy (Controls). Our
results showed that Attriters differed from Controls in their acceptability
judgment ratings and ERP responses when relative clause constructions were
ungrammatical in English, though grammatical in Italian. Controls' ERP responses
to unpreferred sentence constructions were consistent with garden path effects
typically observed in the literature for these complex sentences. In contrast,
due to L2-English influence, Attriters were less sensitive to semantic cues than
to word-order preferences, and processed permissible Italian sentences as
outright morphosyntactic violations. Key factors modulating processing
differences within Attriters were the degree of maintained L1 exposure, length of
residence in the L2 environment and L2 proficiency - with higher levels of L2
immersion and proficiency associated with increased L2 influence on the L1. To
our knowledge, this is the first demonstration that high levels of L2 proficiency
and exposure may render a grammatical sentence in one's native language
ungrammatical. These group differences strongly point to distinct processing
strategies and provide evidence that even a "stabilized" L1 grammar is subject to
change after a prolonged period of L2 immersion and reduced L1 use, especially in
linguistic areas promoting cross-linguistic influence.
PMID- 28424635
TI - Preferential Processing of Social Features and Their Interplay with Physical
Saliency in Complex Naturalistic Scenes.
AB - According to so-called saliency-based attention models, attention during free
viewing of visual scenes is particularly allocated to physically salient image
regions. In the present study, we assumed that social features in complex
naturalistic scenes would be processed preferentially irrespective of their
physical saliency. Therefore, we expected worse prediction of gazing behavior by
saliency-based attention models when social information is present in the visual
field. To test this hypothesis, participants freely viewed color photographs of
complex naturalistic social (e.g., including heads, bodies) and non-social (e.g.,
including landscapes, objects) scenes while their eye movements were recorded. In
agreement with our hypothesis, we found that social features (especially heads)
were heavily prioritized during visual exploration. Correspondingly, the presence
of social information weakened the influence of low-level saliency on gazing
behavior. Importantly, this pattern was most pronounced for the earliest
fixations indicating automatic attentional processes. These findings were further
corroborated by a linear mixed model approach showing that social features
(especially heads) add substantially to the prediction of fixations beyond
physical saliency. Taken together, the current study indicates gazing behavior
for naturalistic scenes to be better predicted by the interplay of social and
physically salient features than by low-level saliency alone. These findings
strongly challenge the generalizability of saliency-based attention models and
demonstrate the importance of considering social influences when investigating
the driving factors of human visual attention.
PMID- 28424637
TI - Listening Niches across a Century of Popular Music.
AB - This article investigates the contexts, or "listening niches", in which people
hear popular music. The study spanned a century of popular music, divided into 10
decades, with participants born between 1940 and 1999. It asks about whether they
know and like the music in each decade, and their emotional reactions. It also
asks whether the music is associated with personal memories and, if so, with whom
they were listening, or whether they were listening alone. Finally, it asks what
styles of music they were listening to, and the music media they were listening
with, in different periods of their lives. The results show a regular progression
through the life span of listening with different individuals (from parents to
children) and with different media (from records to streaming services). A number
of effects found in previous studies were replicated, but the study also showed
differences across the birth cohorts. Overall, there was a song specific age
effect with preferences for music of late adolescence and early adulthood;
however, this effect was stronger for the older participants. In general, music
of the 1940s, 1960s, and 1980s was preferred, particularly among younger
participants. Music of these decades also produced the strongest emotional
responses, and the most frequent and specific personal memories. When growing up,
the participants tended to listen to the older music on the older media, but
rapidly shifted to the new music technologies in their late teens and early 20s.
Younger listeners are currently listening less to music alone than older
listeners, suggesting an important role of socially sharing music, but they also
report feeling sadder when listening to music. Finally, the oldest listeners had
the broadest taste, liking music that they had been exposed to during their
lifetimes in different listening niches.
PMID- 28424636
TI - The Neural Basis of Speech Perception through Lipreading and Manual Cues:
Evidence from Deaf Native Users of Cued Speech.
AB - We present here the first neuroimaging data for perception of Cued Speech (CS) by
deaf adults who are native users of CS. CS is a visual mode of communicating a
spoken language through a set of manual cues which accompany lipreading and
disambiguate it. With CS, sublexical units of the oral language are conveyed
clearly and completely through the visual modality without requiring hearing. The
comparison of neural processing of CS in deaf individuals with processing of
audiovisual (AV) speech in normally hearing individuals represents a unique
opportunity to explore the similarities and differences in neural processing of
an oral language delivered in a visuo-manual vs. an AV modality. The study
included deaf adult participants who were early CS users and native hearing users
of French who process speech audiovisually. Words were presented in an event
related fMRI design. Three conditions were presented to each group of
participants. The deaf participants saw CS words (manual + lipread), words
presented as manual cues alone, and words presented to be lipread without manual
cues. The hearing group saw AV spoken words, audio-alone and lipread-alone. Three
findings are highlighted. First, the middle and superior temporal gyrus
(excluding Heschl's gyrus) and left inferior frontal gyrus pars triangularis
constituted a common, amodal neural basis for AV and CS perception. Second,
integration was inferred in posterior parts of superior temporal sulcus for audio
and lipread information in AV speech, but in the occipito-temporal junction,
including MT/V5, for the manual cues and lipreading in CS. Third, the perception
of manual cues showed a much greater overlap with the regions activated by CS
(manual + lipreading) than lipreading alone did. This supports the notion that
manual cues play a larger role than lipreading for CS processing. The present
study contributes to a better understanding of the role of manual cues as support
of visual speech perception in the framework of the multimodal nature of human
communication.
PMID- 28424638
TI - The Acquisition of Orthographic Knowledge: Evidence from the Lexicality Effects
on N400.
AB - This study aimed to understand how reading ability shapes the lexicality effects
on N400. Fifty-three typical developing children from the second to the sixth
grades were asked to perform the pronounceability judgment task on a set of
Chinese real characters (RC), pseudocharacters (PC) and non-characters (NC), as
ERPs were recorded. The cluster-based permutation analysis revealed that children
with low- to medium-reading ability showed greater negativity to NCs than to RCs
and PCs in frontal sites from 300 to 450 ms, while children with high ability
group showed a greater positivity to NCs than both RCs and PCs at central to
posterior sites. Furthermore, the linear mixed model (LMM) analysis was applied
to investigate the relationship between lexicality effects on N400 and reading
related behavioral assessments on a set of standardized tests (including
character recognition, vocabulary size, phonological awareness, and working
memory). The results found that in children with lower reading ability, the N400
elicited by NCs becomes more negative in the frontal sites. For children with
higher reading ability, the N400 elicited by NCs became more positive than that
elicited by RCs or PCs in the posterior sites. These findings demonstrate the
developmental changes in the lexicality effects on N400 as children become more
advanced readers and suggested that the lexicality effects on N400 can serve as
neural markers for the evaluation of orthographic proficiency in reading
development.
PMID- 28424640
TI - Redefining Critical Thinking: Teaching Students to Think like Scientists.
PMID- 28424639
TI - Inconsistent Effect of Arousal on Early Auditory Perception.
AB - Mood has been shown to influence cognitive performance. However, little is known
about the influence of mood on sensory processing, specifically in the auditory
domain. With the current study, we sought to investigate how auditory processing
of neutral sounds is affected by the mood state of the listener. This was tested
in two experiments by measuring masked-auditory detection thresholds before and
after a standard mood-induction procedure. In the first experiment (N = 76), mood
was induced by imagining a mood-appropriate event combined with listening to mood
inducing music. In the second experiment (N = 80), imagining was combined with
affective picture viewing to exclude any possibility of confounding the results
by acoustic properties of the music. In both experiments, the thresholds were
determined by means of an adaptive staircase tracking method in a two-interval
forced-choice task. Masked detection thresholds were compared between
participants in four different moods (calm, happy, sad, and anxious), which
enabled differentiation of mood effects along the dimensions arousal and
pleasure. Results of the two experiments were analyzed both in separate analyses
and in a combined analysis. The first experiment showed that, while there was no
impact of pleasure level on the masked threshold, lower arousal was associated
with lower threshold (higher masked sensitivity). However, as indicated by an
interaction effect between experiment and arousal, arousal did have a different
effect on the threshold in Experiment 2. Experiment 2 showed a trend of arousal
in opposite direction. These results show that the effect of arousal on auditory
masked sensitivity may depend on the modality of the mood-inducing stimuli. As
clear conclusions regarding the genuineness of the arousal effect on the masked
threshold cannot be drawn, suggestions for further research that could clarify
this issue are provided.
PMID- 28424641
TI - Are Individuals Luck Egalitarians? - An Experiment on the Influence of Brute and
Option Luck on Social Preferences.
AB - According to luck egalitarianism, inequalities should be deemed fair as long as
they follow from individuals' deliberate and fully informed choices (i.e., option
luck) while inequalities should be deemed unfair if they follow from choices over
which the individual has no control (i.e., brute luck). This study investigates
if individuals' fairness preferences correspond with the luck egalitarian
fairness position. More specifically, in a laboratory experiment we test how
individuals choose to redistribute gains and losses that stem from option luck
compared to brute luck. A two-stage experimental design with real incentives was
employed. We show that individuals (n = 226) change their action associated with
re-allocation depending on the underlying conception of luck. Subjects in the
brute luck treatment equalized outcomes to larger extent (p = 0.0069). Thus,
subjects redistributed a larger amount to unlucky losers and a smaller amount to
lucky winners compared to equivalent choices made in the option luck treatment.
The effect is less pronounced when conducting the experiment with third-party
dictators, indicating that there is some self-serving bias at play. We conclude
that people have fairness preference not just for outcomes, but also for how
those outcomes are reached. Our findings are potentially important for
understanding the role citizens assign individual responsibility for life
outcomes, i.e., health and wealth.
PMID- 28424642
TI - Response: Commentary: Incubation and Intuition in Creative Problem Solving.
PMID- 28424643
TI - Oral Storytelling as Evidence of Pedagogy in Forager Societies.
AB - Teaching is reportedly rare in hunter-gatherer societies, raising the question of
whether it is a species-typical trait in humans. A problem with past studies is
that they tend to conceptualize teaching in terms of Western pedagogical
practices. In contrast, this study proceeds from the premise that teaching
requires the ostensive manifestation of generalizable knowledge: the teacher must
signal intent to share information, indicate the intended recipient, and transmit
knowledge that is applicable beyond the present context. Certain features of
human communication appear to be ostensive in function (e.g., eye contact,
pointing, contingency, prosodic variation), and collectively serve as "natural
pedagogy." Tellingly, oral storytelling in forager societies typically employs
these and other ostensive behaviors, and is widely reported to be an important
source of generalizable ecological and social knowledge. Despite this, oral
storytelling has been conspicuously overlooked in studies of teaching in
preliterate societies. Accordingly, this study presents evidence that oral
storytelling involves the use of ostension and the transmission of generic
knowledge, thereby meeting the criteria of pedagogy.
PMID- 28424644
TI - The Association between Parenting Behavior and Executive Functioning in Children
and Young Adolescents.
AB - Executive functioning (EF) is associated with various aspects of school
achievement and cognitive development in children and adolescents. There has been
substantial research investigating associations between EF and other factors in
young children, such as support processes and parenting, but less research has
been conducted about external factors relating to EF in older children and
adolescents. Therefore, the present study investigates one possible factor that
could correlate with EF in school-age children and adolescents: parenting
behavior. The cross-sectional study design gathered data from 169 children in
primary schools, middle-schools, and Gymnasien, and their corresponding parents.
All children underwent a standardized task to measure EF, the computer-based
Erikson Flanker task, which evaluates EF as a function of error rates and
response time. A self-report questionnaire was used to assess parenting behavior.
Multilevel analysis was implemented to test the effects of parenting behavior on
EF in school-age children. The results show significant associations between
various parenting behaviors and children's EF: High scores on parental
involvement or parental responsibility are associated with low error rates on the
Erikson Flanker task, whereas high parental scores on inconsistent discipline are
associated with high error rates. These correlations between parenting behavior
and EF remained significant despite controlling for child age, maternal
education, family income, and baseline performance (i.e., congruent trials on the
Erikson Flanker task). No associations were found between parental behavior and
reaction time on the Erikson Flanker task. These results indicate the important
association between parenting behaviors and EF skills in school-age children, and
foster the necessity to inform parents about ways in which they can optimally
support their children's cognitive development.
PMID- 28424645
TI - Cerebellar tDCS Does Not Enhance Performance in an Implicit Categorization
Learning Task.
AB - Background: Transcranial Direct Current Stimulation (tDCS) is a form of non
invasive electrical stimulation that changes neuronal excitability in a polarity
and site-specific manner. In cognitive tasks related to prefrontal and cerebellar
learning, cortical tDCS arguably facilitates learning, but the few studies
investigating cerebellar tDCS, however, are inconsistent. Objective: We
investigate the effect of cerebellar tDCS on performance of an implicit
categorization learning task. Methods: Forty participants performed a
computerized version of an implicit categorization learning task where squares
had to be sorted into two categories, according to an unknown but fixed rule that
integrated both the size and luminance of the square. Participants did one round
of categorization to familiarize themselves with the task and to provide a
baseline of performance. After that, 20 participants received anodal tDCS (20
min, 1.5 mA) over the right cerebellum, and 19 participants received sham
stimulation and simultaneously started a second session of the categorization
task using a new rule. Results: As expected, subjects performed better in the
second session than in the first, baseline session, showing increased accuracy
scores and reduced reaction times. Over trials, participants learned the
categorization rule, improving their accuracy and reaction times. However, we
observed no effect of anodal tDCS stimulation on overall performance or on
learning, compared to sham stimulation. Conclusion: These results suggest that
cerebellar tDCS does not modulate performance and learning on an implicit
categorization task.
PMID- 28424646
TI - Duration Aftereffect Depends on the Duration of Adaptation.
AB - It has been widely demonstrated that a prolonged adaptation to a relatively long
or short stimulus leads to a robust repulsive duration aftereffect. However,
little is known about the rapid adaptation to stimulus duration. In this study,
we investigated whether the duration aftereffect could also be induced by short
term adaptation to stimuli of both sub- and supra-second durations. To control
for the internal reference for duration judgment, participants were adapted to a
stimulus of medium duration, and then tested with both longer and shorter
stimuli. We found that the duration aftereffect was only observed after long-term
adaptation to stimuli of both sub- and supra-second durations, which suggests
that the exposure time to the adaptor is a fundamental factor in determining the
duration aftereffect. Our findings offer further evidence of the duration
aftereffect, which in this study was dissociated from the anchor effect and high
level aftereffects.
PMID- 28424648
TI - Effects of Outcome Predictability on Human Learning.
PMID- 28424647
TI - Bringing Back the Balance: Domain-General Processes Are Also Important in
Numerical Cognition.
PMID- 28424649
TI - Connections of Grasping and Horizontal Hand Movements with Articulation in Czech
Speakers.
AB - We have recently shown in Finnish speakers that articulation of certain vowels
and consonants has a systematic influence on simultaneous grasp actions as well
as on forward and backward hand movements. Here we studied whether these effects
generalize to another language, namely Czech. We reasoned that if the results
generalized to another language environment, it would suggest that the effects
arise through other processes than language-dependent semantic associations.
Rather, the effects would be likely to arise through language-independent
interactions between processes that plan articulatory gestures and hand
movements. Participants were presented with visual stimuli specifying
articulations to be uttered (e.g., A or I), and they were required to produce a
manual response concurrently with the articulation. In Experiment 1 they
responded with a precision or a power grip, whereas in Experiment 2 they
responded with a forward or a backward hand movement. The grip congruency effect
was fully replicated: the consonant [k] and the vowel [alpha] were associated
with power grip responses, while the consonant [t] and the vowel [i] were
associated with precision grip responses. The forward/backward congruency effect
was replicated with vowels [alpha], [o], which were associated with backward
movement and with [i], which was associated with forward movement, but not with
consonants [k] and [t]. These findings suggest that the congruency effects mostly
reflect interaction between processes that plan articulatory gestures and hand
movements with an exception that the forward/backward congruency effect might
only work with vowel articulation.
PMID- 28424651
TI - Racial Assumptions Color the Mental Representation of Social Class.
AB - We investigated the racial content of perceivers' mental images of different
socioeconomic categories. We selected participants who were either high or low in
prejudice toward the poor. These participants saw 400 pairs of visually noisy
face images. Depending on condition, participants chose the face that looked like
a poor person, a middle income person, or a rich person. We averaged the faces
selected to create composite images of each social class. A second group of
participants rated the stereotypical Blackness of these images. They also rated
the face images on a variety of psychological traits. Participants high in
economic prejudice produced strongly class-differentiated mental images. They
imagined the poor to be Blacker than middle income and wealthy people. They also
imagined them to have less positive psychological characteristics. Participants
low in economic prejudice also possessed images of the wealthy that were
relatively White, but they represented poor and middle class people in a less
racially differentiated way. We discuss implications for understanding the
intersections of race and class in social perception.
PMID- 28424650
TI - The Role of the Left Anterior Temporal Lobe for Unpredictable and Complex
Mappings in Word Reading.
AB - The anterior temporal lobes (ATLs) have been consistently associated with
semantic processing which, in turn, has a key role in reading aloud single words.
This study aimed to investigate (1) the reading abilities in patients with the
semantic variant of primary progressive aphasia (svPPA), and (2) the relationship
between gray matter (GM) volume of the left ATL and word reading performance
using voxel-based morphometry (VBM). Three groups of participants (svPPA,
Alzheimer's Disease, AD and healthy elderly adults) performed a reading task with
exception words, regular words and pseudowords, along with a structural magnetic
resonance imaging scan. For exception words, the svPPA group had a lower accuracy
and a greater number of regularization errors as compared to the control groups
of healthy participants and AD patients. Similarly, for regular words, svPPA
patients had a lower accuracy in comparison with AD patients, and a greater
number of errors related to complex orthography-to-phonology mappings (OPM) in
comparison to both control groups. VBM analyses revealed that GM volume of the
left ATL was associated with the number of regularization errors. Also, GM volume
of the left lateral ATL was associated with the number of errors with complex OPM
during regular word reading. Our results suggest that the left ATL might play a
role in the reading of exception words, in accordance with its role in semantic
processing. Results further support the involvement of the left lateral ATL in
combinatorial processes, including the integration of semantic and phonological
information, for both exception and regular words.
PMID- 28424652
TI - Quantitative Electroencephalographic Biomarkers in Preclinical and Human Studies
of Huntington's Disease: Are They Fit-for-Purpose for Treatment Development?
AB - A major focus in development of novel therapies for Huntington's disease (HD) is
identification of treatments that reduce the burden of mutant huntingtin (mHTT)
protein in the brain. In order to identify and test the efficacy of such
therapies, it is essential to have biomarkers that are sensitive to the effects
of mHTT on brain function to determine whether the intervention has been
effective at preventing toxicity in target brain systems before onset of clinical
symptoms. Ideally, such biomarkers should have a plausible physiologic basis for
detecting the effects of mHTT, be measureable both in preclinical models and
human studies, be practical to measure serially in clinical trials, and be
reliably measurable in HD gene expansion carriers (HDGECs), among other features.
Quantitative electroencephalography (qEEG) fulfills many of these basic criteria
of a "fit-for-purpose" biomarker. qEEG measures brain oscillatory activity that
is regulated by the brain structures that are affected by mHTT in premanifest and
early symptom individuals. The technology is practical to implement in the
laboratory and is well tolerated by humans in clinical trials. The biomarkers are
measureable across animal models and humans, with findings that appear to be
detectable in HDGECs and translate across species. We review here the literature
on recent developments in both preclinical and human studies of the use of qEEG
biomarkers in HD, and the evidence for their usefulness as biomarkers to help
guide development of novel mHTT lowering treatments.
PMID- 28424653
TI - Disentangling Stigma from Functional Neurological Disorders: Conference Report
and Roadmap for the Future.
AB - A multidisciplinary expert review of key issues and future directions from the
conference "Controversial labels and clinical uncertainties: psychogenic
disorders, conversion disorder, and functional symptoms." On October 9 and 10,
2015, a conference entitled "Controversial labels and clinical uncertainties:
psychogenic disorders, conversion disorder, and functional symptoms" was held at
the Center for Ethics, Emory University, Atlanta, GA, USA. This conference
brought together a select group of 30 distinguished thought leaders and
practitioners, including ethicists, researchers, clinicians, humanities scholars,
and advocates to discuss the unique challenges and controversies related to the
diagnosis, treatment, and stigma for patients with what is currently recognized
as functional ("psychogenic") neurological disorders. Our group of experts
explored the conflicts and ethical tensions within health care that must be
addressed in order to advance care for these disorders. What follows is a
reflection on the conversations between conference attendees outlining key
challenges and value conflicts in the diagnosis and treatment of patients with
functional disorders. With this report, we aim to provide a roadmap for reducing
stigma and improving care for functional neurological disorders (FND). A path
forward would involve (1) setting a multifactorial research agenda that equally
prioritized access to effective psychotherapy as well as identification of novel
biomarkers; (2) empowering patients with FND to be heard and to drive changes in
care; and (3) reducing isolation for clinicians by providing formal training and
setting up multidisciplinary care teams and support networks.
PMID- 28424654
TI - Emerging Approaches for Validating and Managing Multiple Sclerosis Relapse.
AB - The autoimmune disease multiple sclerosis (MS) is characterized by relapses in
the majority of patients. A definitive clinical diagnosis of relapse in MS can be
complicated by the presence of an infection or comorbid disorder. In this mini
review, we describe efforts to develop enhanced imaging techniques and biomarker
detection as future tools for relapse validation. There is emerging evidence of
roles for meningeal inflammation, sex hormones, comorbid metabolic or mood
disorders, and a dysregulated immune profile in the manifestation and severity of
relapse. Specific subsets of immune cells likely drive the pathophysiology of
relapse, and identification of a patient's unique immunological signature of
relapse may help guide future diagnosis and treatment. Finally, these studies
highlight the diversity in terms of relapse presentation, immunological
signature, and response in patients with MS, indicating that going forward the
best approach to assessment and treatment of relapse will be multifactorial and
highly personalized.
PMID- 28424656
TI - Empirical Comparison of Diffusion Kurtosis Imaging and Diffusion Basis Spectrum
Imaging Using the Same Acquisition in Healthy Young Adults.
AB - As diffusion tensor imaging gains widespread use, many researchers have been
motivated to go beyond the tensor model and fit more complex diffusion models, to
gain a more complete description of white matter microstructure and associated
pathology. Two such models are diffusion kurtosis imaging (DKI) and diffusion
basis spectrum imaging (DBSI). It is not clear which DKI parameters are most
closely related to DBSI parameters, so in the interest of enabling comparisons
between DKI and DBSI studies, we conducted an empirical survey of the
interrelation of these models in 12 healthy volunteers using the same diffusion
acquisition. We found that mean kurtosis is positively associated with the DBSI
fiber ratio and negatively associated with the hindered ratio. This was primarily
driven by the radial component of kurtosis. The axial component of kurtosis was
strongly and specifically correlated with the restricted ratio. The joint spatial
distributions of DBSI and DKI parameters are tissue-dependent and stable across
healthy individuals. Our contribution is a better understanding of the biological
interpretability of the parameters generated by the two models in healthy
individuals.
PMID- 28424655
TI - Sustained and Transient Vestibular Systems: A Physiological Basis for
Interpreting Vestibular Function.
AB - Otolithic afferents with regular resting discharge respond to gravity or low
frequency linear accelerations, and we term these the static or sustained
otolithic system. However, in the otolithic sense organs, there is anatomical
differentiation across the maculae and corresponding physiological
differentiation. A specialized band of receptors called the striola consists of
mainly type I receptors whose hair bundles are weakly tethered to the overlying
otolithic membrane. The afferent neurons, which form calyx synapses on type I
striolar receptors, have irregular resting discharge and have low thresholds to
high frequency (e.g., 500 Hz) bone-conducted vibration and air-conducted sound.
High-frequency sound and vibration likely causes fluid displacement which
deflects the weakly tethered hair bundles of the very fast type I receptors.
Irregular vestibular afferents show phase locking, similar to cochlear afferents,
up to stimulus frequencies of kilohertz. We term these irregular afferents the
transient system signaling dynamic otolithic stimulation. A 500-Hz vibration
preferentially activates the otolith irregular afferents, since regular afferents
are not activated at intensities used in clinical testing, whereas irregular
afferents have low thresholds. We show how this sustained and transient
distinction applies at the vestibular nuclei. The two systems have differential
responses to vibration and sound, to ototoxic antibiotics, to galvanic
stimulation, and to natural linear acceleration, and such differential
sensitivity allows probing of the two systems. A 500-Hz vibration that
selectively activates irregular otolithic afferents results in stimulus-locked
eye movements in animals and humans. The preparatory myogenic potentials for
these eye movements are measured in the new clinical test of otolith function
ocular vestibular-evoked myogenic potentials. We suggest 500-Hz vibration may
identify the contribution of the transient system to vestibular controlled
responses, such as vestibulo-ocular, vestibulo-spinal, and vestibulo-sympathetic
responses. The prospect of particular treatments targeting one or the other of
the transient or sustained systems is now being realized in the clinic by the use
of intratympanic gentamicin which preferentially attacks type I receptors. We
suggest that it is valuable to view vestibular responses by this sustained
transient distinction.
PMID- 28424657
TI - Magnetic Vestibular Stimulation (MVS) As a Technique for Understanding the Normal
and Diseased Labyrinth.
AB - Humans often experience dizziness and vertigo around strong static magnetic
fields such as those present in an MRI scanner. Recent evidence supports the idea
that this effect is the result of inner ear vestibular stimulation and that the
mechanism is a magnetohydrodynamic force (Lorentz force) that is generated by the
interactions between normal ionic currents in the inner ear endolymph and the
strong static magnetic field of MRI machines. While in the MRI, the Lorentz force
displaces the cupula of the lateral and anterior semicircular canals, as if the
head was rotating with a constant acceleration. If a human subject's eye
movements are recorded when they are in darkness in an MRI machine (i.e., without
fixation), there is a persistent nystagmus that diminishes but does not
completely disappear over time. When the person exits the magnetic field, there
is a transient aftereffect (nystagmus beating in the opposite direction) that
reflects adaptation that occurred in the MRI. This magnetic vestibular
stimulation (MVS) is a useful technique for exploring set-point adaptation, the
process by which the brain adapts to a change in its environment, which in this
case is vestibular imbalance. Here, we review the mechanism of MVS, how MVS
produces a unique stimulus to the labyrinth that allows us to explore set-point
adaptation, and how this technique might apply to the understanding and treatment
of vestibular and other neurological disorders.
PMID- 28424658
TI - beta- and alpha2-Adrenoceptor Control of Vascular Tension and Catecholamine
Release in Female Normotensive and Spontaneously Hypertensive Rats.
AB - As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower
blood pressure than male SHR. In male, normotensive rats (WKY), alpha2- and
beta1+2-adrenoceptors (AR) reciprocally controlled catecholamine release and
vascular smooth muscle tension. This interaction was malfunctioning in male SHR.
The present study analyzed if a favorable shift in the alpha2/beta1+2AR
interaction may represent an antihypertensive protection in females. Female SHR
(early hypertension, 12-14 weeks) and age-matched WKY were infused with tyramine
(15 min) to stimulate norepinephrine (NE) release through the reuptake
transporter, consequently preventing reuptake. Presynaptic control of vesicular
release was therefore reflected as differences in overflow to plasma. The
released NE increased total peripheral vascular resistance (TPR). The results
showed that beta1>2AR facilitated tyramine-stimulated NE release in both strains,
also in the presence of alpha2AR-antagonist (L-659,066). betaAR-antagonist
(atenolol-beta1, ICI-118551-beta2, nadolol-beta1+2) had no effect on the
increased secretion of epinephrine after L-659,066 in WKY, but beta1>2AR
antagonist augmented the L-659,066-induced increase in the secretion of
epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater
effect in WKY than SHR, whereas beta1or2-selective antagonists did not. One
betaAR-subtype may therefore substitute for the other. When both beta1+2AR were
blocked, alpha2AR-antagonist still reduced the TPR response in WKY but not SHR.
Thus, alpha2/beta1+2AR reciprocally controlled catecholamine release, with a
particular negative beta1AR-influence on alpha2AR-auto-inhibition of epinephrine
secretion in SHR. Moreover, in these female rats, beta1/2AR-independent alpha2AR
mediated vasoconstriction was seen in WKY but not SHR, but beta1/2AR-mediated
vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also
in SHR.
PMID- 28424659
TI - Online Measurement of Microembolic Signal Burden by Transcranial Doppler during
Catheter Ablation for Atrial Fibrillation-Results of a Multicenter Trial.
AB - INTRODUCTION: Left atrial pulmonary vein isolation (PVI) is an accepted treatment
option for patients with symptomatic atrial fibrillation (AF). This procedure can
be complicated by stroke or silent cerebral embolism. Online measurement of
microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for
characterizing thromboembolic burden during PVI. In this prospective multicenter
trial, we investigated the burden, characteristics, and composition of MES during
left atrial catheter ablation using a variety of catheter technologies. MATERIALS
AND METHODS: PVI was performed in a total of 42 patients using the circular
shaped multielectrode pulmonary vein ablation catheter (PVAC) technology in 23,
an irrigated radiofrequency (IRF) in 14, and the cryoballoon (CB) technology in 5
patients. TCD was used to detect the total MES burden and sustained
thromboembolic showers (TESs) of >30 s. During TES, the site of ablation within
the left atrium was registered. MES composition was classified manually into
"solid," "gaseous," or "equivocal" by off-line expert assessment. RESULTS: The
total MES burden was higher when using IRF compared to CB (2,336 +/- 1,654 vs.
593 +/- 231; p = 0.007) and showed a tendency toward a higher burden when using
IRF compared to PVAC (2,336 +/- 1,654 vs. 1,685 +/- 2,255; p = 0.08). TES
occurred more often when using PVAC compared to IRF (1.5 +/- 2 vs. 0.4 +/- 1.3; p
= 0.04) and most frequently when ablation was performed close to the left
superior pulmonary vein (LSPV). Of the MES, 17.004 (23%) were characterized as
definitely solid, 13.204 (18%) as clearly gaseous, and 44.366 (59%) as equivocal.
DISCUSSION: We investigated the burden and characteristics of MES during left
atrial catheter ablation for AF. All ablation techniques applied in this study
generated a relevant number of MES. There was a significant difference in total
MES burden using IRF compared to CB and a tendency toward a higher burden using
IRF compared to PVAC. The highest TES burden was found in the PVAC group,
particularly during ablation close to the LSPV. The composition of thromboembolic
particles was balanced. The impact of MES, TES, and composition of thromboembolic
particles on neurological outcome needs to be evaluated further. (Clinical Trial
Registration: Deutsches Register Klinischer Studien, https://drks-neu.uniklinik
freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003465.
DRKS00003465.).
PMID- 28424660
TI - CCL2/Monocyte Chemoattractant Protein 1 and Parathyroid Hormone Action on Bone.
AB - Chemokines are small molecules that play a crucial role as chemoattractants for
several cell types, and their components are associated with host immune
responses and repair mechanisms. Chemokines selectively recruit monocytes,
neutrophils, and lymphocytes and induce chemotaxis through the activation of G
protein-coupled receptors. Two well-described chemokine families (CXC and CC) are
known to regulate the localization and trafficking of immune cells in cases of
injury, infection, and tumors. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is
one of the important chemokines from the CC family that controls migration and
infiltration of monocytes/macrophages during inflammation. CCL2 is profoundly
expressed in osteoporotic bone and prostate cancer-induced bone resorption. CCL2
also regulates physiological bone remodeling in response to hormonal and
mechanical stimuli. Parathyroid hormone (PTH) has multifaceted effects on bone,
depending on the mode of administration. Intermittent PTH increases bone in vivo
by increasing the number and activity of osteoblasts, whereas a continuous
infusion of PTH decreases bone mass by stimulating a net increase in bone
resorption. CCL2 is essential for both anabolic and catabolic effects of PTH. In
this review, we will discuss the pharmacological role of PTH and involvement of
CCL2 in the processes of PTH-mediated bone remodeling.
PMID- 28424661
TI - Gonadotropin-Inhibitory Hormone Plays Roles in Stress-Induced Reproductive
Dysfunction.
AB - Physical and psychological stressors suppress hypothalamic-pituitary-gonadal axis
activity and sexual behavior and consequently induce reproductive dysfunction.
Recently, it has been shown that gonadotropin-inhibitory hormone (GnIH), also
called RFamide-related peptide 3 (RFRP) in mammals, which is a potent inhibitory
regulator of gonadotropin-releasing hormone (GnRH) and gonadotropin, is involved
in stress-induced reproductive dysfunction. GnIH/Rfrp (the gene coding RFRP-3)
expression and activity are increased by psychological and immune stress, and
this alteration suppresses GnRH and gonadotropin secretion. Glucocorticoid acts
as a mediator that interacts between stress and hypothalamic GnIH/RFRP-3.
GnIH/RFRP-3 also plays important roles in stress-induced suppression of sexual
behavior and infertility, and genetic silencing of GnIH/Rfrp completely recovers
sexual behavior and fertility. This review summarizes what is currently known
about the roles of GnIH in stress-induced reproductive dysfunction.
PMID- 28424662
TI - Untangling Genomes of Novel Planctomycetal and Verrucomicrobial Species from
Monterey Bay Kelp Forest Metagenomes by Refined Binning.
AB - The kelp forest of the Pacific temperate rocky marine coastline of Monterey Bay
in California is a dominant habitat for large brown macro-algae in the order of
Laminariales. It is probably one of the most species-rich, structurally complex
and productive ecosystems in temperate waters and well-studied in terms of
trophic ecology. However, still little is known about the microorganisms thriving
in this habitat. A growing body of evidence suggests that bacteria associated
with macro-algae represent a huge and largely untapped resource of natural
products with chemical structures that have been optimized by evolution for
biological and ecological purposes. Those microorganisms are most likely
attracted by algae through secretion of specific carbohydrates and proteins that
trigger them to attach to the algal surface and to form biofilms. The algae might
then employ those bacteria as biofouling control, using their antimicrobial
secondary metabolites to defeat other bacteria or eukaryotes. We here analyzed
biofilm samples from the brown macro-algae Macrocystis pyrifera sampled in
November 2014 in the kelp forest of Monterey Bay by a metagenomic shotgun and
amplicon sequencing approach, focusing on Planctomycetes and Verrucomicrobia from
the PVC superphylum. Although not very abundant, we were able to find novel
Planctomycetal and Verrucomicrobial species by an innovative binning approach.
All identified species harbor secondary metabolite related gene clusters,
contributing to our hypothesis that through inter-species interaction,
microorganisms might have a substantial effect on kelp forest wellbeing and/or
disease-development.
PMID- 28424663
TI - Antimicrobial Photodynamic Therapy against Endodontic Enterococcus faecalis and
Candida albicans Mono and Mixed Biofilms in the Presence of Photosensitizers: A
Comparative Study with Classical Endodontic Irrigants.
AB - Endodontic biofilms eradication from the infected root canal system remains as
the primary focus in endodontic field. In this study, it was assessed the
efficacy of antimicrobial Photodynamic Therapy (aPDT) with the Zn(II)chlorin e6
methyl ester (Zn(II)e6Me) activated by red light against monospecies and mixed
biofilms of Enterococcus faecalis and Candida albicans. The results were compared
with the ones obtained with Rose Bengal (RB), Toluidine Blue-O (TBO), the
synthetic tetracationic porphyrin (TMPyP) as well as classical endodontic
irrigants (3% NaOCl, 17% EDTA and 2% CHX). The antimicrobial efficacy of aPDT
toward monospecies and mixed biofilms was quantified resorting to safranin red
method. The changes of biofilm organization and of cellular ultrastructure were
evaluated through several microscopy techniques (light, laser confocal and
transmission electron microscopy). Zn(II)e6Me once activated with light for 60 or
90 s was able to remove around 60% of the biofilm's biomass. It was more
efficient than TBO and RB and showed similar efficiency to TMPyP and classical
irrigants, CHX and EDTA. As desirable in a PS, Zn(II)e6Me in the dark showed
smaller activity than TMPyP. Only NaOCl revealed higher efficiency, with 70-90%
of the biofilm's biomass removal. The organization of biofilms and the normal
microbial cell ultrastructure were extensively damaged by the presence of
Zn(II)e6Me. aPDT with Zn(II)e6Me showed to be an efficient antimicrobial strategy
deserving further studies leading to a future clinical usage in endodontic
disinfection.
PMID- 28424664
TI - Spotted Fever: Epidemiology and Vector-Rickettsia-Host Relationship in Rio de
Janeiro State.
AB - The eco-epidemiological scenario of spotted fever (SF), a tick-borne disease that
affects humans and other animals in several countries around the world, was
analyzed in Rio de Janeiro (RJ) State, Brazil. During the last 34 years, 990 SF
cases were reported in RJ (the Brazilian state with the highest population
density), including 116 cases confirmed by serology (RIFI) or PCR, among 42.39%
of the municipalities with reported cases of SF. The epidemiologic dynamics of SF
in RJ State are very heterogeneous in time and space, with outbreaks, high
mortality rates and periods of epidemiological silence (no SF cases reported).
Furthermore, it exhibited a changing epidemiological profile from being rural to
becoming an urban disease. This study identified arthropods infected with
Rickettsia felis, R. bellii and R. rickettsii, and found that the abundance of
ectoparasites was associated with specific hosts. The R. rickettsii-vector-host
relationship was most evident in species-specific parasitism. This suggests that
the association between dogs, cattle, horses, capybaras and their main
ectoparasites, Rhipicephalus sanguineus and Ctenocephalides felis, Rhipicephalus
microplus, Dermacentor nitens, and Amblyomma dubitatum, respectively, has a key
role in the dynamics of R. rickettsii transmission in enzootic cycles and the
maintenance of carrier ectoparasites, thus facilitating the existence of endemic
areas with the ability to produce epidemic outbreaks of SF in RJ. This study
found confirmed human infections for only the R. rickettsii carrier Amblyomma
sculptum, which reinforces the importance of this species as a vector of the
pathogen in Brazil. This study can be adapted to different eco-epidemiological
scenarios of spotted fever throughout the Americas.
PMID- 28424665
TI - Ca. Similichlamydia in Epitheliocystis Co-infection of Gilthead Seabream Gills:
Unique Morphological Features of a Deep Branching Chlamydial Family.
AB - The Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) bacterial superphylum
constitutes a broad range of organisms with an intriguing array of
ultrastructural morphologies, including intracellular membranes and compartments
and their corresponding complex genomes encoding these forms. The phylum
Chlamydiae are all obligate intracellular bacteria and, although much is already
known of their genomes from various families and how these regulate the various
morphological forms, we know remarkably little about what is likely the deepest
rooting clade of this phylum, which has only been found to contain pathogens of
marine and fresh water vertebrates. The disease they are associated with is
called epitheliocystis; however, analyses of the causative agents is hindered by
an inability to cultivate them for refined in vitro experimentation. For this
reason, we have developed tools to analyse both the genomes and the
ultrastructures of bacteria causing this disease, directly from infected tissues.
Here we present structural data for a member of the family Ca.
Similichlamydiaceae from this deep-rooted clade, which we have identified using
molecular tools, in epitheliocystis lesions of gilthead seabream (Sparus aurata)
in Greece. We present evidence that the chlamydial inclusions appear to develop
in a perinuclear location, similar to other members of the phylum and that a
chlamydial developmental cycle is present, with chlamydial forms similar to
reticular bodies (RBs) and elementary bodies (EBs) detected. Division of the RBs
appeared to follow a budding process, and larger RBs with multiple condensed
nucleoids were detected using both transmission electron microscopy (TEM) and by
focused-ion beam, scanning electron microscopy (FIB-SEM). As model hosts, fish
offer many advantages for investigation, and we hope by these efforts to
encourage others to explore the biology of fish pathogens from the PVC.
PMID- 28424667
TI - Editorial: Plant Immunity against Viruses.
PMID- 28424666
TI - NapA Mediates a Redox Regulation of the Antioxidant Response, Carbon Utilization
and Development in Aspergillus nidulans.
AB - The redox-regulated transcription factors (TFs) of the bZIP AP1 family, such as
yeast Yap1 and fission yeast Pap1, are activated by peroxiredoxin proteins (Prxs)
to regulate the antioxidant response. Previously, Aspergillus nidulans mutants
lacking the Yap1 ortholog NapA have been characterized as sensitive to H2O2 and
menadione. Here we study NapA roles in relation to TFs SrrA and AtfA, also
involved in oxidant detoxification, showing that these TFs play different roles
in oxidative stress resistance, catalase gene regulation and development, during
A. nidulans life cycle. We also uncover novel NapA roles in repression of sexual
development, normal conidiation, conidial mRNA accumulation, and carbon
utilization. The phenotypic characterization of DeltagpxA, DeltatpxA, and
DeltatpxB single, double and triple peroxiredoxin mutants in wild type or
DeltanapA backgrounds shows that none of these Prxs is required for NapA function
in H2O2 and menadione resistance. However, these Prxs participate in a minor NapA
independent H2O2 resistance pathway and NapA and TpxA appear to regulate
conidiation along the same route. Using transcriptomic analysis we show that
during conidial development NapA-dependent gene expression pattern is different
from canonical oxidative stress patterns. In the course of conidiation, NapA is
required for regulation of at least 214 genes, including ethanol utilization
genes alcR, alcA and aldA, and large sets of genes encoding proteins involved in
transcriptional regulation, drug detoxification, carbohydrate utilization and
secondary metabolism, comprising multiple oxidoreductases, membrane transporters
and hydrolases. In agreement with this, DeltanapA mutants fail to grow or grow
very poorly in ethanol, arabinose or fructose as sole carbon sources. Moreover,
we show that NapA nuclear localization is induced not only by oxidative stress
but also by growth in ethanol and by carbon starvation. Together with our
previous work, these results show that SakA-AtfA, SrrA and NapA oxidative stress
sensing pathways regulate essential aspects of spore physiology (i.e., cell cycle
arrest, dormancy, drug production and detoxification, and carbohydrate
utilization).
PMID- 28424668
TI - Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its
Breakdown in Early Resuscitation Phase.
AB - Under gradual acidification of growth medium resulting in the formation of
dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in
dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64%
of total organic substances in the dormant cell extract was represented by
trehalose whilst the trehalose content in an extract of active cells taken from
early stationary phase was not more than 15%. Trehalose biosynthesis during
transition to the dormant state is provided by activation of genes involved in
the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the
concentration of free trehalose in dormant cells by expression of MSMEG_4535
coding for trehalase we found that cell viability depends on trehalose level:
cells with a high amount of trehalose survive much better than cells with a low
amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose
and an increase in glucose concentration occurred in the early period of
resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes
place at this time as a transient increase in trehalase activity was observed
between 1 and 3 h of resuscitation. Activation of trehalase was not due to de
novo biosynthesis but because of self-activation of the enzyme from the inactive
state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents
self-activation of trehalase in vitro and after activation the enzyme is still
sensitive to ATP we suggest that the transient character of trehalase activation
in cells is due to variation in intracellular ATP concentration found in the
early resuscitation period. The negative influence of the trehalase inhibitor
validamycin A on the resuscitation of dormant cells proves the importance of
trehalase for resuscitation. These experiments demonstrate the significance of
free trehalose accumulation for the maintenance of dormant mycobacterial
viability and the involvement of trehalose breakdown in early events leading to
cell reactivation similar to yeast and fungal spores.
PMID- 28424669
TI - Inferring Microbial Interactions in the Gut of the Hong Kong Whipping Frog
(Polypedates megacephalus) and a Validation Using Probiotics.
AB - The concerted activity of intestinal microbes is crucial to the health and
development of their host organisms. Investigation of microbial interactions in
the gut should deepen our understanding of how these micro-ecosystems function.
Due to advances in Next Generation Sequencing (NGS) technologies, various
bioinformatic strategies have been proposed to investigate these microbial
interactions. However, due to the complexity of the intestinal microbial
community and difficulties in monitoring their interactions, at present there is
a gap between the theory and biological application. In order to construct and
validate microbial relationships, we first induce a community shift from simple
to complex by manipulating artificial hibernation (AH) in the treefrog
Polypedates megacephalus. To monitor community growth and microbial interactions,
we further performed a time-course screen using a 16S rRNA amplicon approach and
a Lotka-Volterra model. Lotka-Volterra models, also known as predator-prey
equations, predict the dynamics of microbial communities and how communities are
structured and sustained. An interaction network of gut microbiota at the genus
level in the treefrog was constructed using Metagenomic Microbial Interaction
Simulator (MetaMIS) package. The interaction network obtained had 1,568
commensal, 1,737 amensal, 3,777 mutual, and 3,232 competitive relationships,
e.g., Lactococcus garvieae has a commensal relationship with Corynebacterium
variabile. To validate the interacting relationships, the gut microbe composition
was analyzed after probiotic trials using single strain (L. garvieae, C.
variabile, and Bacillus coagulans, respectively) and a combination of L.
garvieae, C. variabile, and B. coagulans, because of the cooperative relationship
among their respective genera identified in the interaction network. After a 2
week trial, we found via 16S rRNA amplicon analysis that the combination of
cooperative microbes yielded significantly higher probiotic concentrations than
single strains, and the immune response (interleukin-10 expression) also
significantly changed in a manner consistent with improved probiotic effects. By
taking advantage of microbial community shift from simple to complex, we thus
constructed a reliable microbial interaction network, and validated it using
probiotic strains as a test system.
PMID- 28424670
TI - Azathioprine, Mercaptopurine, and 5-Aminosalicylic Acid Affect the Growth of IBD
Associated Campylobacter Species and Other Enteric Microbes.
AB - Campylobacter concisus is a bacterium that is associated with inflammatory bowel
disease (IBD). Immunosuppressive drugs including azathioprine (AZA) and
mercaptopurine (MP), and anti-inflammatory drug such as 5-aminosalicylic acid (5
ASA) are commonly used to treat patients with IBD. This study aimed to examine
the effects of AZA, MP, and 5-ASA on the growth of IBD-associated bacterial
species and to identify bacterial enzymes involved in immunosuppressive drug
metabolism. A total of 15 bacterial strains of five species including 11 C.
concisus strains, Bacteroides fragilis, Bacteroides vulgatus, Enterococcus
faecalis, and Escherichia coli were examined. The impact of AZA, MP, and 5-ASA on
the growth of these bacterial species was examined quantitatively using a plate
counting method. The presence of enzymes involved in AZA and MP metabolism in
these bacterial species was identified using bioinformatics tools. AZA and MP
significantly inhibited the growth of all 11 C. concisus strains. C. concisus
strains were more sensitive to AZA than MP. 5-ASA showed inhibitory effects to
some C. concisus strains, while it promoted the growth of other C. concisus
strains. AZA and MP also significantly inhibited the growth of B. fragilis and B.
vulgatus. The growth of E. coli was significantly inhibited by 200 MUg/ml of AZA
as well as 100 and 200 MUg/ml of 5-ASA. Bacterial enzymes related to AZA and MP
metabolism were found, which varied in different bacterial species. In
conclusion, AZA and MP have inhibitory effects to IBD-associated C. concisus and
other enteric microbes, suggesting an additional therapeutic mechanism of these
drugs in the treatment of IBD. The strain dependent differential impact of 5-ASA
on the growth of C. concisus may also have clinical implication given that in
some cases 5-ASA medications were found to cause exacerbations of colitis.
PMID- 28424671
TI - Functional Characterization and Conditional Regulation of the Type VI Secretion
System in Vibrio fluvialis.
AB - Vibrio fluvialis is an emerging foodborne pathogen of increasing public health
concern. The mechanism(s) that contribute to the bacterial survival and disease
are still poorly understood. In other bacterial species, type VI secretion
systems (T6SSs) are known to contribute to bacterial pathogenicity by exerting
toxic effects on host cells or competing bacterial species. In this study, we
characterized the genetic organization and prevalence of two T6SS gene clusters
(VflT6SS1 and VflT6SS2) in V. fluvialis. VflT6SS2 harbors three "orphan" hcp-vgrG
modules and was more prevalent than VflT6SS1 in our isolates. We showed that
VflT6SS2 is functionally active under low (25 degrees C) and warm (30 degrees C)
temperatures by detecting the secretion of a T6SS substrate, Hcp. This finding
suggests that VflT6SS2 may play an important role in the survival of the
bacterium in the aquatic environment. The secretion of Hcp is growth phase
dependent and occurs in a narrow range of the growth phase (OD600 from 1.0 to
2.0). Osmolarity also regulates the function of VflT6SS2, as evidenced by our
finding that increasing salinity (from 170 to 855 mM of NaCl) and exposure to
high osmolarity KCl, sucrose, trehalose, or mannitol (equivalent to 340 mM of
NaCl) induced significant secretion of Hcp under growth at 30 degrees C.
Furthermore, we found that although VflT6SS2 was inactive at a higher temperature
(37 degrees C), it became activated at this temperature if higher salinity
conditions were present (from 513 to 855 mM of NaCl), indicating that it may be
able to function under certain conditions in the infected host. Finally, we
showed that the functional expression of VflT6SS2 is associated with anti
bacterial activity. This activity is Hcp-dependent and requires vasH, a
transcriptional regulator of T6SS. In sum, our study demonstrates that VflT6SS2
provides V. fluvialis with an enhanced competitive fitness in the marine
environment, and its activity is regulated by environmental signals, such as
temperature and osmolarity.
PMID- 28424672
TI - Isolation and Identification of the Indigenous Yeast Population during
Spontaneous Fermentation of Isabella (Vitis labrusca L.) Grape Must.
AB - Grape must harbors a complex community of yeast species responsible for
spontaneous alcoholic fermentation. Although there are detailed studies on the
microbiota of Vitis vinifera L. grapes, less is known about the diversity and
behavior of yeast communities present on fermenting grape must from other species
of Vitis. In this work, we used a culture-dependent method to study the identity
and dynamics of the indigenous yeast population present during the spontaneous
fermentation of Isabella (Vitis labrusca L.) grape must. Alcoholic fermentation
was conducted using standard enological practices, and the associated non
Saccharomyces and S. cerevisiae yeast community was analyzed using selective
growth media and 5.8-ITS DNA sequencing. Candida californica, Candida hellenica,
Starmerella bacillaris (synonym Candida zemplinina), Hanseniaspora uvarum, and
Hanseniaspora vineae were the main non-Saccharomyces species identified on
Isabella fermenting must. Issatchenkia hanoiensis, a yeast species rarely found
on Vitis vinifera L. grapes, was also recognized on Isabella grape must. Candida
azymoides, Candida californica and Pichia cecembensis, identified in this work on
Isabella fermenting must, have not previously been found on Vitis vinifera L.
grape must. Interestingly, C. azymoides, I. hanoiensis and P. cecembensis have
recently been isolated from the surface of Vitis labrusca L. grapes from
vineyards in the Azores archipelago, suggesting that specific Vitis-yeast species
associations are formed independently of geographic origin. We suggest that C.
azymoides, C. californica, and P. cecembensis are yeast species preferentially
associated with Vitis labrusca L. grapes. Specific biological interactions
between grapevines and yeast species may underlie the assembly of differential
Vitis-microbial communities.
PMID- 28424673
TI - Genome-Scale Reconstruction of the Metabolic Network in Oenococcus oeni to Assess
Wine Malolactic Fermentation.
AB - Oenococcus oeni is the main responsible agent for malolactic fermentation in
wine, an unpredictable and erratic process in winemaking. To address this, we
have constructed and exhaustively curated the first genome-scale metabolic model
of Oenococcus oeni, comprising 660 reactions, 536 metabolites and 454 genes. In
silico experiments revealed that nutritional requirements are predicted with an
accuracy of 93%, while 14 amino acids were found to be essential for the growth
of this bacterial species. When the model was applied to determine the non-growth
associated maintenance, results showed that O. oeni grown at 12% ethanol
concentration spent 30 times more ATP to stay alive than in the absence of
ethanol. Most of this ATP is employed for extruding protons outside of the cell.
A positive relationship was also found between specific consumption rates of
fructose, amino acids, oxygen, and malic acid and the specific production rates
of erythritol, lactate, and acetate, according to the ethanol content of the
medium. The metabolic model reconstructed here represents a unique tool to
predict the successful completion of wine malolactic fermentation carried out
either by different strains of Oenococcus oeni, as well as at any particular
physico-chemical composition of wine. It will also allow the development of
consortium metabolic models that could be applied to winemaking to simulate and
understand the interactions between O. oeni and other microorganisms that share
this ecological niche.
PMID- 28424675
TI - Safety, Protective Immunity, and DIVA Capability of a Rough Mutant Salmonella
Pullorum Vaccine Candidate in Broilers.
AB - Salmonella enterica subsp. enterica serovar Gallinarum biovar Pullorum
(Salmonella Pullorum) is highly adapted to chickens causing an acute systemic
disease that results in high mortality. Vaccination represents one approach for
promoting animal health, food safety and reducing environmental persistence in
Salmonella control. An important consideration is that Salmonella vaccination in
poultry should not interfere with the salmonellosis monitoring program. This is
the basis of the DIVA (Differentiation of Infected and Vaccinated Animals)
program. In order to achieve this goal, waaL mutant was developed on a spiC
mutant that was developed previously. The safety, efficacy, and DIVA features of
this vaccine candidate (Salmonella Pullorum DeltaspiCDeltawaaL) were evaluated in
broilers. Our results show that the truncated LPS in the vaccine strain has a
differentiating use as both a bacteriological marker (rough phenotype) and also
as a serological marker facilitating the differentiation between infected and
vaccinated chickens. The rough mutant showed adequate safety being avirulent in
the host chicks and showed increased sensitivity to environmental stresses.
Single intramuscular immunization of day-old broiler chicks with the mutant
confers ideal protection against lethal wild type challenge by significantly
stimulating both humoral and cellular immune responses as well as reducing the
colonization of the challenge strain. Significantly lower mean pathology scores
were observed in the vaccination group compared to the control group.
Additionally, the mutant strain generated cross-protection against challenge with
the wild type Salmonella Gallinarum thereby improving survival and with the wild
type Salmonella Enteritidis thereby reducing colonization. These results suggest
that the double-mutant strain may be a safe, effective, and cross-protective
vaccine against Salmonella infection in chicks while conforming to the
requirements of the DIVA program.
PMID- 28424674
TI - Global Fecal and Plasma Metabolic Dynamics Related to Helicobacter pylori
Eradication.
AB - Background:Helicobacter pylori colonizes the gastric mucosa of more than half of
the world's population. There is increasing evidence H. pylori protects against
the development of obesity and childhood asthma/allergies in which the
development of these diseases coincide with transient dysbiosis. However, the
mechanism underlying the association of H. pylori eradication with human
metabolic and immunological disorders is not well-established. In this study, we
aimed to investigate the local and systemic effects of H. pylori eradication
through untargeted fecal lipidomics and plasma metabolomics approaches by liquid
chromatography mass spectrometry (LC-MS). Results: Our study revealed that
eradication of H. pylori eradication (i.e., loss of H. pylori and/or H. pylori
eradication therapy) changed many global metabolite/lipid features, with the
majority being down-regulated. Our findings primarily show that H. pylori
eradication affects the host energy and lipid metabolism which may eventually
lead to the development of metabolic disorders. Conclusion: These predictive
metabolic signatures of metabolic and immunological disorders following H. pylori
eradication can provide insights into dynamic local and systemic metabolism
related to H. pylori eradication in modulating human health.
PMID- 28424676
TI - Seasonal Fluctuations of Microbial Aerosol in Live Poultry Markets and the
Detection of Endotoxin.
AB - Microbial aerosol whose species and concentrations are closely related to human
health is ubiquitous. The effect of microbes on human and animal health and
production performance is, in many cases, caused by the spreading of air. Samples
in this experiment were from a live poultry market (LPM) in Tai'an, China,
collected three times a day (8 am, 14 pm, and 20 pm) over three consecutive days
each month for 11 months (Original sampling plan was a year, the government due
to the environmental protection, the was LPM closed). The main indicators of the
test were concentrations of cultural airborne bacteria, airborne fungi, and Gram
negative bacteria. At the same time the species of Gram-negative bacteria and the
concentration of endotoxin were tested. Temperature and humidity were recorded in
the process of each sampling. The results showed that the diurnal variation of
the concentration of bacteria, fungi, and Gram-negative bacteria is higher in the
morning and evening, but lower at noon. The concentrations of airborne bacteria
and Gram-negative bacteria increased in earlier months and decreased in later
months, with the peak appearing in the autumn. The concentration of fungi showed
a decrease first and then tended to stabilize, with the peak occurring in the
spring. The concentration peak of endotoxin occurred in the summer. Endotoxin
levels were significantly correlated with humidity (r = 0.90, p < 0.01). Most
bacteria were distributed at the third and fourth stages (2.1-4.7 MUm) in the
ANDERSEN-6 sampler. The dominant species of Gram-negative bacteria during the
four seasons were Pseudomonas aeruginosa, Acinetobacter, Klebsiella pneumoniae,
and Salmonella. In China, people have a habit of eating fresh poultry, LPM
distribution is widespread, stream of people and traffic flow are large, easily
caused the spread of bacteria and viruses, so the LPM microbial aerosol research
have significant public health implications.
PMID- 28424677
TI - Responses of the Housefly, Musca domestica, to the Hytrosavirus Replication:
Impacts on Host's Vitellogenesis and Immunity.
AB - Hytrosaviridae family members replicate in the salivary glands (SGs) of their
adult dipteran hosts and are transmitted to uninfected hosts via saliva during
feeding. Despite inducing similar gross symptoms (SG hypertrophy; SGH),
hytrosaviruses (SGHVs) have distinct pathobiologies, including sex-ratio
distortions in tsetse flies and refusal of infected housefly females to copulate.
Via unknown mechanism(s), SGHV replication in other tissues results in reduced
fecundity in tsetse flies and total shutdown of vitellogenesis and sterility in
housefly females. We hypothesized that vitellogenesis shutdown was caused by
virus-induced modulation of hormonal titers. Here, we used RNA-Seq to investigate
virus-induced modulation of host genes/pathways in healthy and virus-infected
houseflies, and we validated expression of modulated genes (n = 23) by RT-qPCR.
We also evaluated the levels and activities of hemolymph AMPs, levels of
endogenous sesquiterpenoids, and impacts of exogenous hormones on ovarian
development in viremic females. Of the 973 housefly unigenes that were
significantly modulated (padj <= 0.01, log2FC <= -2.0 or >= 2.0), 446 and 527
genes were downregulated and upregulated, respectively. While the most
downregulated genes were related to reproduction (embryogenesis/oogenesis), the
repertoire of upregulated genes was overrepresented by genes related to non-self
recognition, ubiquitin-protease system, cytoskeletal traffic, cellular
proliferation, development and movement, and snRNA processing. Overall, the
virus, Musca domestica salivary gland hytrosavirus (MdSGHV), induced the
upregulation of various components of the siRNA, innate antimicrobial immune, and
autophagy pathways. We show that MdSGHV undergo limited morphogenesis in the
corpora allata/corpora cardiaca (CA/CC) complex of M. domestica. MdSGHV
replication in CA/CC potentially explains the significant reduction of hemolymph
sesquiterpenoids levels, the refusal to mate, and the complete shutdown of egg
development in viremic females. Notably, hormonal rescue of vitellogenesis did
not result in egg production. The mechanism underlying MdSGHV-induced sterility
has yet to be resolved.
PMID- 28424678
TI - Microbial and Isotopic Evidence for Methane Cycling in Hydrocarbon-Containing
Groundwater from the Pennsylvania Region.
AB - The Pennsylvania region hosts numerous oil and gas reservoirs and the presence of
hydrocarbons in groundwater has been locally observed. However, these methane
containing freshwater ecosystems remain poorly explored despite their potential
importance in the carbon cycle. Methane isotope analysis and analysis of low
molecular weight hydrocarbon gases from 18 water wells indicated that active
methane cycling may be occurring in methane-containing groundwater from the
Pennsylvania region. Consistent with this observation, multigenic qPCR and gene
sequencing (16S rRNA genes, mcrA, and pmoA genes) indicated abundant populations
of methanogens, ANME-2d (average of 1.54 * 104mcrA gene per milliliter of water)
and bacteria associated with methane oxidation (NC10, aerobic methanotrophs,
methylotrophs; average of 2.52 * 103pmoA gene per milliliter of water). Methane
cycling therefore likely represents an important process in these hydrocarbon
containing aquifers. The microbial taxa and functional genes identified and
geochemical data suggested that (i) methane present is at least in part due to
methanogens identified in situ; (ii) Potential for aerobic and anaerobic methane
oxidation is important in groundwater with the presence of lineages associated
with both anaerobic an aerobic methanotrophy; (iii) the dominant methane
oxidation process (aerobic or anaerobic) can vary according to prevailing
conditions (oxic or anoxic) in the aquifers; (iv) the methane cycle is closely
associated with the nitrogen cycle in groundwater methane seeps with methane
and/or methanol oxidation coupled to denitrification or nitrate and nitrite
reduction.
PMID- 28424679
TI - Linking Diet to Colorectal Cancer: The Emerging Role of MicroRNA in the
Communication between Plant and Animal Kingdoms.
AB - Environmental and lifestyle factors, including diet and nutritional habits have
been strongly linked to colorectal cancer (CRC). Of note, unhealthy dietary
habits leading to adiposity represent a main risk factor for CRC and are
associated with a chronic low-grade inflammatory status. Inflammation is a
hallmark of almost every type of cancer and can be modulated by several food
compounds exhibiting either protective or promoting effects. However, in spite of
an extensive research, the underlying mechanisms by which dietary patterns or
bioactive food components may influence tumor onset and outcome have not been
fully clarified yet. Growing evidence indicates that diet, combining beneficial
substances and potentially harmful ingredients, has an impact on the expression
of key regulators of gene expression such as the non-coding RNA (ncRNA). Since
the expression of these molecules is deranged in chronic inflammation and cancer,
modulating their expression may strongly influence the cancer phenotype and
outcomes. In addition, the recently acquired knowledge on the existence of
intricate inter-kingdom communication networks, is opening new avenues for a
deeper understanding of the intimate relationships linking diet to CRC. In this
novel scenario, diet-modulated ncRNA may represent key actors in the interaction
between plant and animal kingdoms, capable of influencing disease onset and
outcome. In this review, we will summarize the studies demonstrating a link
between bioactive food components, including food-derived, microbiota-processed,
secondary metabolites, and host ncRNA. We will focus on microRNA, highlighting
how this plant/animal inter-kingdom cross-talk may have an impact on CRC
establishment and progression.
PMID- 28424680
TI - Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside
Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in
Lipid Nanoparticle (LNP).
AB - RNA-based vaccine represents an irresistible and safe immunization strategy with
decreasing theoretical risks of genomic integration and malignant cell
transformation. To our knowledge, however, there is no report about development
of RNA vaccine against Toxoplasma gondii infection. We have previously
demonstrated that the recombinant T. gondii nucleoside triphosphate hydrolase-II
(NTPase-II) protein is able to provide protective Th1 cell-mediated immunity
against T. gondii. Herein, we evaluated the immunogenic potential of a self
amplifying RNA vaccine-encoding T. gondii NTPase-II gene, RREP-NTPase-II,
delivered by a synthetic lipid nanoparticle (LNP). Immunization of mice with
naked RREP-NTPase-II induced a strong cellular and humoral immune response with
high-IgG antibody titers and IFN-gamma production. The immunized mice displayed
significantly prolonged survival time and reduction in brain parasite load
(46.4%) compared with control group. Furthermore, mice vaccinated with RREP
NTPase-II-encapsulated LNP displayed significantly enhanced protection against
acute infection as well as chronic infection with PRU cyst, which shows 62.1%
reduction in brain cyst burden in comparison to control group. These results
suggest that the combination of self-amplifying RNA and LNP ion would be
beneficial to the development of a safe and long-acting vaccine against
toxoplasmosis.
PMID- 28424681
TI - The Spontaneous Autoimmune Neuromyopathy in ICOSL-/- NOD Mice Is CD4+ T-Cell and
Interferon-gamma Dependent.
AB - Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of
diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the
development of a spontaneous autoimmune neuromyopathy. At the pathological level,
ICOSL-/- NOD mice show stronger protection from insulitis than their ICOS-/-
counterparts. Also, the ICOSL-/- NOD model carries a limited C57BL/6 region
containing the Icosl nul mutation, but, in contrast to ICOS-/- NOD mice, no gene
variant previously reported as associated to NOD diabetes. Therefore, we aimed at
providing a detailed characterization of the ICOSL-/- NOD model. The phenotype
observed in ICOSL-/- NOD mice is globally similar to that observed in ICOS-/- and
ICOS-/-ICOSL-/- double-knockout NOD mice, manifested by a progressive locomotor
disability first affecting the front paws as observed by catwalk analysis and a
decrease in grip test performance. The pathology remains limited to peripheral
nerve and striated muscle. The muscle disease is characterized by myofiber
necrosis/regeneration and an inflammatory infiltrate composed of CD4+ T-cells,
CD8+ T-cells, and myeloid cells, resembling human myositis. Autoimmune
neuromyopathy can be transferred to NOD.scid recipients by CD4+ but not by CD8+ T
cells isolated from 40-week-old female ICOSL-/- NOD mice. The predominant role of
CD4+ T-cells is further demonstrated by the observation that neuromyopathy does
not develop in CIITA-/-ICOSL-/- NOD in contrast to beta2microglobulin-/-ICOSL-/-
NOD mice. Also, the cytokine profile of CD4+ T-cells infiltrating muscle and
nerve of ICOSL-/- NOD mice is biased toward a Th1 pattern. Finally, adoptive
transfer experiments show that diabetes development requires expression of ICOSL,
in contrast to neuromyopathy. Altogether, the deviation of autoimmunity from the
pancreas to skeletal muscles in the absence of ICOS/ICOSL signaling in NOD mice
is strictly dependent on CD4+ T-cells, leads to myofiber necrosis and
regeneration. It provides the first mouse model of spontaneous autoimmune
myopathy akin to human myositis.
PMID- 28424683
TI - Novel Strategy to Expand Super-Charged NK Cells with Significant Potential to
Lyse and Differentiate Cancer Stem Cells: Differences in NK Expansion and
Function between Healthy and Cancer Patients.
AB - Natural killer (NK) cells are known to target cancer stem cells and
undifferentiated tumors. In this paper, we provide a novel strategy for expanding
large numbers of super-charged NK cells with significant potential to lyse and
differentiate cancer stem cells and demonstrate the differences in the dynamics
of NK cell expansion between healthy donors and cancer patients. Decline in
cytotoxicity and lower interferon (IFN)-gamma secretion by osteoclast (OC)
expanded NK cells from cancer patients correlates with faster expansion of
residual contaminating T cells within purified NK cells, whereas healthy donors'
OCs continue expanding super-charged NK cells while limiting T cell expansion for
up to 60 days. Similar to patient NK cells, NK cells from tumor-bearing BLT
humanized mice promote faster expansion of residual T cells resulting in
decreased numbers and function of NK cells, whereas NK cells from mice with no
tumor continue expanding NK cells and retain their cytotoxicity. In addition,
dendritic cells (DCs) in contrast to OCs are found to promote faster expansion of
residual T cells within purified NK cells resulting in the decline in NK cell
numbers from healthy individuals. Addition of anti-CD3 mAb inhibits T cell
proliferation while enhancing NK cell expansion; however, expanding NK cells have
lower cytotoxicity but higher secretion of IFN-gamma. Expansion and functional
activation of super-charged NK cells by OCs is dependent on interleukin (IL)-12
and IL-15. Thus, in this report, we not only provide a novel strategy to expand
super-charged NK cells, but also demonstrate that rapid and sustained expansion
of residual T cells within the purified NK cells during expansion with DCs or OCs
could be a potential mechanism by which the numbers and function of NK cells
decline in cancer patients and in BLT-humanized mice.
PMID- 28424684
TI - Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates
KIR2DS1 Recognition by Natural Killer Cells.
AB - The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human
leukocyte antigen (HLA) class I molecules has been characterized in detail. By
contrast, activating members of the KIR family, although closely related to
inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1
is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA
C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell
reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a
modified DAP12 adaptor protein. KIR2DS1 reporter cells were not activated upon
coculture with 721.221 cells transfected with different HLA-C molecules, or with
interferon-gamma stimulated primary dermal fibroblasts. However, KIR2DS1 reporter
cells and KIR2DS1+ primary natural killer (NK) cells were activated by C2-HLA-C
homozygous human fetal foreskin fibroblasts (HFFFs) but only after infection with
specific clones of a clinical strain of human cytomegalovirus (HCMV). Active
viral gene expression was required for activation of both cell types. Primary
NKG2A-KIR2DS1+ NK cell subsets degranulated after coculture with HCMV-infected
HFFFs. The W6/32 antibody to HLA class I blocked the KIR2DS1 reporter cell
interaction with its ligand on HCMV-infected HFFFs but did not block interaction
with KIR2DL1. This implies a differential recognition of HLA-C by KIR2DL1 and
KIR2DS1. The data suggest that modulation of HLA-C by HCMV is required for a
potent KIR2DS1-mediated NK cell activation.
PMID- 28424685
TI - Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients
with Autoimmune Atypical Hemolytic Uremic Syndrome.
AB - INTRODUCTION: In autoimmune atypical hemolytic uremic syndrome (aHUS), the
complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of
the patients carry a homozygous deletion of its homolog complement FH-related
protein 1 (CFHR1). The functional consequence of FH-blockade is widely
established; however, the molecular basis of autoantibody binding and the role of
CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope
mapping of FH to provide structural insight in the autoantibody recruitment on FH
and potentially CFHR1. METHODS: Eight anti-FH positive aHUS patients were
enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we
located the amino acids (aa) involved in binding of acute and convalescence stage
autoantibodies. We confirmed the location of the mapped epitopes using
recombinant FH domains 19-20 that carried single-aa substitutions at the
suspected antibody binding sites in three of our patients. Location of the linear
epitopes and the introduced point mutations was visualized using crystal
structures of the corresponding domains of FH and CFHR1. RESULTS: We identified
three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one
on CFHR1 (aa276-290) that are recognized both in the acute and convalescence
stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS
specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our
patients being deficient for CFHR1. Epitope mapping with the domain constructs
validated the location of the linear epitopes on FH with a distinct autoantibody
binding motif within aa1183-1198 in line with published observations. SUMMARY:
According to the results, the linear epitopes we identified are located close to
each other on the crystal structure of FH domains 19-20. This tertiary
configuration contains the amino acids reported to be involved in C3b and sialic
acid binding on the regulator, which may explain the functional deficiency of FH
in the presence of autoantibodies. The data we provide identify the exact
structures involved in autoantibody recruitment on FH and confirm the presence of
an autoantibody binding epitope on CFHR1.
PMID- 28424682
TI - Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis:
Lessons Learned from Autoimmune Diseases.
AB - The classical paradigm of tuberculosis (TB) immunity, with a central protective
role for Th1 responses and IFN-gamma-stimulated cellular responses, has been
challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1
immunity. Moreover, preclinical TB models have shown that increasing IFN-gamma
responses in the lungs is more damaging to the host than to the pathogen. Type 1
interferon signaling and altered Th17 responses have also been associated with
active TB, but their functional roles in TB pathogenesis remain to be
established. These two host responses have been studied in more detail in
autoimmune diseases (AID) and show functional interactions that are of potential
interest in TB immunity. In this review, we first identify the role of type 1
interferons and Th17 immunity in TB, followed by an overview of interactions
between these responses observed in systemic AID. We discuss (i) the effects of
GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii)
convergence of IL-17 and type 1 interferon signaling on stimulating B-cell
activating factor production and the central role of neutrophils in this process;
and (iii) synergy between IL-17 and type 1 interferons in the generation and
function of tertiary lymphoid structures and the associated follicular helper T
cell responses. Evaluation of these autoimmune-related pathways in TB
pathogenesis provides a new perspective on recent developments in TB research.
PMID- 28424686
TI - Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1-2 Co
Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens.
AB - Consecutive cases of human infection with H7N9 influenza viruses since 2013 in
China have prompted efforts to develop an effective treatment. Subunit vaccines
introduced by intranasal administration can block an infection at its primary
site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent
adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein
consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused
with Salmonella typhimurium fliC. In the present study, we investigated its
effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9
influenza subunit vaccine. Mice immunized intranasally with HA1-2-fliC and HA1-2
PEI showed higher HA1-2-specific immunoglobulin (Ig)G and IgA titers in serum,
nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation
and proliferation and the number of HA1-2-specific interferon (IFN)-gamma- and
interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and
PEI groups; in the latter, there were more cells secreting IL-4 than IFN-gamma,
suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and
PEI induced Th2-biased responses, consistent with the serum antibody isotype
pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a
chicken model. The results showed that chickens receiving fliC and PEI adjuvant
vaccine exhibited robust immune responses leading to a significant reduction in
viral loads of throat and cloaca compared to chickens receiving only HA1-2. These
findings provide a basis for the development of H7N9 influenza HA1-2 mucosal
subunit vaccines.
PMID- 28424687
TI - CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident
Memory Transcriptional Profile.
AB - During chronic infection, memory T cells acquire a unique phenotype and become
dependent on different survival signals than those needed for memory T cells
generated during an acute infection. The distinction between the role of effector
and memory T cells in an environment of persistent antigen remains unclear. Here,
in the context of chronic Toxoplasma gondii infection, we demonstrate that a
population of CD8 T cells exhibiting a tissue-resident memory (TRM) phenotype
accumulates within the brain. We show that this population is distributed
throughout the brain in both parenchymal and extraparenchymal spaces.
Furthermore, this population is transcriptionally distinct and exhibits a
transcriptional signature consistent with the TRM observed in acute viral
infections. Finally, we establish that the CD103+ TRM population has an intrinsic
capacity to produce both IFN-gamma and TNF-alpha, cytokines critical for parasite
control within the central nervous system (CNS). The contribution of this
population to pro-inflammatory cytokine production suggests an important role for
TRM in protective and ongoing immune responses in the infected CNS. Accession
number: GSE95105.
PMID- 28424689
TI - Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during
Inflammatory Gum Disease.
AB - Periodontal inflammation is one of the most common chronic inflammatory
conditions in humans. Despite recent advances in identifying and characterizing
oral microbiota dysbiosis in the pathogenesis of gum disease, just how host
factors maintain a healthy homeostatic oral microbial community or prevent the
development of a pathogenic oral microbiota remains poorly understood. An
important determinant of microbiota fate is local antimicrobial proteins. Here,
we report that chemoattractant protein chemerin, which we recently identified as
a potent endogenous antimicrobial agent in body barriers such as the skin, is
present in the oral cavity under homeostatic and inflammatory conditions.
Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against
select bacteria strategically positioned in dental biofilm. Gingival crevicular
samples from patients with gingivitis but not periodontitis contain abundant
bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration.
Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin.
Together, these data suggest that as an antimicrobial agent and leukocyte
chemoattractant, chemerin likely contributes to antimicrobial immune defense in
the oral cavity.
PMID- 28424688
TI - Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New
Perspectives of Antimicrobial Peptide-Based Therapies.
AB - While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there
are concerns regarding possible side effects related to the unwanted suppression
of antimicrobial immunity leading to an increased risk of infection. Conversely,
recent data show that MSCs exert strong antimicrobial effects through indirect
and direct mechanisms, partially mediated by the secretion of antimicrobial
peptides and proteins (AMPs). In fact, MSCs have been reported to increase
bacterial clearance in preclinical models of sepsis, acute respiratory distress
syndrome, and cystic fibrosis-related infections. This article reviews the
current evidence regarding the direct antimicrobial effector function of MSCs,
focusing mainly on the role of MSCs-derived AMPs. The strategies that might
modulate the expression and secretion of these AMPs, leading to enhanced
antimicrobial effect, are highlighted. Furthermore, studies evaluating the
presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as
perspective opportunities to develop new drug delivery tools. The antimicrobial
potential of MSCs-derived EVs can also be heightened through cell conditioning
and/or drug loading. Finally, improving the pharmacokinetics and delivery, in
addition to deciphering the multi-target drug status of AMPs, should
synergistically lead to key advances against infections caused by drug-resistant
strains.
PMID- 28424690
TI - Bacillus subtilis Improves Immunity and Disease Resistance in Rabbits.
AB - Probiotics such as Lactobacillus and Bifidobacterium have been successfully used
to promote growth and prevent diseases. Previous reports have demonstrated that
Bacillus subtilis (B. subtilis) was a potential probiotic for animals. In this
research, 180 B. subtilis were isolated from the soil, identified, and
investigated in vitro. Furthermore, five B. subtilis were selected and mixed to
investigate their effect on growth performance, immune response, intestine
microbiota, and disease resistance in rabbits. Rabbits with a diet of 106 CFU g-1
mixed B. subtilis exhibited the best growth performance and higher serum IgG and
IgA than controls (P < 0.05). Moreover, dairy with B. subtilis can promote the
balance of intestinal flora. The major proinflammatory factor and beta-defensin
were upregulated compared with the controls. After 7 weeks of feeding, the
survival rate of the rabbits fed with B. subtilis was significantly higher than
those in the control groups postinfected with Escherichia coli. At the same time,
this study detected higher expression of beta-defensin and reduced bacteria
contents of the heart and cecal contents from the diet mixed with B. subtilis
compared with the control groups. In conclusion, dietary supplementation with B.
subtilis for rabbits could improve growth performance, intestinal homeostasis,
and immune organ index and enhance innate immune response as well as disease
resistance. These findings showed that the induction of beta-defensin by B.
subtilis might be an interesting new therapeutic strategy to strengthen innate
defense mechanisms.
PMID- 28424691
TI - Increased Autophagy-Related 5 Gene Expression Is Associated with Collagen
Expression in the Airways of Refractory Asthmatics.
AB - BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a
challenge for treating asthmatic individuals. At present, no drugs can remove or
reduce excessive collagen in asthmatic airways. Hence, the identification of
pathways involved in collagen deposition would help to generate therapeutic
targets to interfere with the airway remodeling process. Autophagy, a cellular
degradation process, has been shown to be dysregulated in various fibrotic
diseases, and genetic association studies in independent human populations have
identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis.
Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic
airways. OBJECTIVE: This study aimed to determine if (1) collagen deposition in
asthmatic airways is associated with ATG5 expression and (2) ATG5 protein
expression is associated with asthma per se and severity. METHODS: Gene
expression of transforming growth factor beta 1, various asthma-related collagen
types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III,
alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and
ATG5 were measured using mRNA isolated from bronchial biopsies of refractory
asthmatic subjects and assessed for pairwise associations. Protein expression of
ATG5 in the airways was measured and associations were assessed for asthma per
se, severity, and lung function. MAIN RESULTS: In refractory asthmatic
individuals, gene expression of ATG5 was positively associated with COL5A1 in the
airways. No association was detected between ATG5 protein expression and asthma
per se, severity, and lung function. CONCLUSION AND CLINICAL RELEVANCE: Positive
correlation between the gene expression patterns of ATG5 and COL5A1 suggests that
dysregulated autophagy may contribute to subepithelial fibrosis in the airways of
refractory asthmatic individuals. This finding highlights the therapeutic
potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat
refractory asthmatic individuals.
PMID- 28424693
TI - Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation.
AB - Evolution of melanoma from a primary tumor to widespread metastasis is crucially
dependent on lymphatic spread. The mechanisms regulating the initial step in
metastatic dissemination via regional lymph nodes remain largely unknown;
however, evidence supporting the establishment of a pre-metastatic niche is
evolving. We have previously described a dysfunctional immune profile including
reduced expression of dendritic cell (DC) maturation markers in the first node
draining from the primary tumor, the sentinel lymph node (SLN). Importantly, this
phenotype is present prior to evidence of nodal metastasis. Herein, we evaluate
melanoma-derived extracellular vesicles (EVs) as potential mediators of the
premetastatic niche through cargo-specific polarization of DCs. DCs matured in
vitro in the presence of melanoma EVs demonstrated significantly impaired
expression of CD83 and CD86 as well as decreased expression of Th1 polarizing
chemokines Flt3L and IL15 and migration chemokines MIP-1alpha and MIP-1beta
compared to liposome-treated DCs. Profiling of melanoma EV cargo identified
shared proteomic and RNA signatures including S100A8 and S100A9 protein cargo,
which in vitro compromised DC maturation similar to melanoma EVs. Early evidence
demonstrates that similar EVs can be isolated from human afferent lymphatic fluid
ex vivo. Taken together, here, we propose melanoma EV cargo as a mechanism by
which DC maturation is compromised warranting further study to consider this as a
potential mechanism enabled by the primary tumor to establish the premetastatic
niche in tumor-draining SLNs of patients.
PMID- 28424692
TI - T Cells in Osteoarthritis: Alterations and Beyond.
AB - Although osteoarthritis (OA) has been traditionally regarded as a non
inflammatory disease, reports increasingly suggest that it is inflammatory, at
least in certain patients. OA patients often exhibit inflammatory infiltration of
synovial membranes by macrophages, T cells, mast cells, B cells, plasma cells,
natural killer cells, dendritic cells, granulocytes, etc. Although previous
reviews have summarized the knowledge of inflammation in the pathogenesis of OA,
as far as we know, no report review our current understanding about T cells,
especially, each T cell subtype, in the biology of OA. This review highlights the
current understanding of the role of T cells in the pathogenesis of OA, with
attention to Th1 cells, Th2 cells, Th9 cells, Th17 cells, Th22 cells, regulatory
T cells, follicular helper T cells, cytotoxic T cells, T memory cells, and even
unconventional T cells (e.g., gammadelta T cells and cluster of differentiation 1
restricted T cells). The findings highlight the importance of T cells to the
development and progression of OA and suggest new therapeutic approaches for OA
patients based on the manipulation of T-cell responses.
PMID- 28424694
TI - Immune Responses in the Central Nervous System Are Anatomically Segregated in a
Non-Human Primate Model of Human Immunodeficiency Virus Infection.
AB - The human immunodeficiency virus (HIV) accesses the central nervous system (CNS)
early during infection, leading to HIV-associated cognitive impairment and
establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory
responses in different CNS regions in simian immunodeficiency virus (SIV)
infected macaques, a model for HIV infection. We found increased expression of
inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV
infected macaques. Conversely, the frontal lobe showed downregulation of
inflammatory genes associated with interferon-gamma and interleukin-6 pathways,
and absence of perivascular cuffing. These immunologic alterations were not
accompanied by differences in SIV transcriptional activity within the tissue.
Altered expression of genes associated with neurotoxicity was observed in both
midbrain and frontal lobe. The segregation of inflammatory responses to specific
regions of the CNS may both account for HIV-associated neurological symptoms and
constitute a critical hurdle for HIV eradication by shielding the CNS viral
reservoir from antiviral immunity.
PMID- 28424695
TI - B Cell Tolerance to Deiminated Histones in BALB/c, C57BL/6, and Autoimmune-Prone
Mouse Strains.
AB - Deimination, a posttranslational modification of arginine to citrulline carried
out by peptidylarginine deiminases, may compromise tolerance of self-antigens.
Patients with connective tissue autoimmunity, particularly rheumatoid arthritis
(RA), systemic lupus erythematosus (SLE), or Felty's syndrome, present with
autoantibodies to deiminated histones (dH), which thus form a category of
antibodies to citrullinated protein antigens (ACPA). In general, ACPA are a
sensitive diagnostic for RA and may form in response to the release of nuclear
chromatin (DNA plus dH) from granulocytes, usually referred to as neutrophil
extracellular traps. The aim of this study was to examine spontaneously
autoimmune mice for autoantibodies and T cell responses to dH. We compared IgG
binding to deiminated and non-deiminated histones (nH) by ELISA and Western
blotting in spontaneously autoimmune strains of (NZB * NZW) F1 and NZM2410
together with their derivative congenic strains, C57BL/6.Sle1 and
C57BL/6.Sle1.Sle3, which display profound autoreactivity against nuclear self
antigens. The splenocyte proliferation against the two antigens was determined in
the spontaneously autoimmune (NZB * NZW) F1 strain from which other autoimmune
strains used in the study were derived. Immunizations with dH and nH were
attempted in BALB/c mice to assess their splenocyte response. Splenocytes from
BALB/c mice and from autoimmune mice at the time of conversion to autoimmunity
proliferated strongly in response to dH, yet serum IgG from autoimmune (NZB *
NZW) F1, NZM2410, and C57BL/6.Sle1.Sle3 mice displayed a remarkable bias against
binding to dH. At the time of seroconversion, the antibodies already exhibited
preference for nH, and only nH were recovered from circulating immune complexes.
Analysis of histone deimination showed constitutive deimination in thymic
extracts from C57BL/6 and C57BL/6.Sle1.Sle2.Sle3 triply congenic mice and in
spleens of autoimmune triply congenic mice. Our study demonstrates that tolerance
mechanisms against dH are intact in BALB/c and C57BL/6 mice and continue to be
effective in mice with overt autoimmunity to nH. We conclude that, in contrast to
human RA and SLE patients, where we frequently observe autoantibodies against dH,
autoimmune mice maintain strong tolerance mechanisms to prevent the development
of autoantibodies to dH.
PMID- 28424698
TI - Editorial: Immuno-Metabolism in Tumor Microenvironment.
PMID- 28424696
TI - Spirochetal Lipoproteins and Immune Evasion.
AB - Spirochetes are a major threat to public health. However, the exact pathogenesis
of spirochetal diseases remains unclear. Spirochetes express lipoproteins that
often determine the cross talk between the host and spirochetes. Lipoproteins are
pro-inflammatory, modulatory of immune responses, and enable the spirochetes to
evade the immune system. In this article, we review the modulatory effects of
spirochetal lipoproteins related to immune evasion. Understanding lipoprotein
induced immunomodulation will aid in elucidating innate pathogenesis processes
and subsequent adaptive mechanisms potentially relevant to spirochetal disease
vaccine development and treatment.
PMID- 28424697
TI - Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions
with Diverse Ligands and Alterations in Splice Variant Expression.
AB - The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44,
and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and
are encoded by the ncr1, ncr2, and ncr3 genes, respectively. NCRs have
classically been defined as activating receptors that trigger cytotoxicity and
cytokine responses by NK cells upon engaging with ligands on tumor cells. Several
new findings, however, have challenged this model and identified alternative
mechanisms regulating the function of NCRs. Recent reports indicate that ligand
matters, since the interaction of NKp44 with distinct ligands on target cells can
either activate or inhibit NK cells. Also, the NCRs have been found to interact
with distinct specificities to various heparan sulfate glycosaminoglycans, which
are complex polysaccharides found in extracellular matrix or on cell surface
heparan sulfate proteoglycans (HSPGs). The NCRs can engage with HSPGs in trans as
a co-ligand on the target cells or in cis on the NK cell surface to regulate
receptor-ligand interactions and NK cell activation. A number of splice variants
of ncr2 and ncr3 have also been identified, and a predominant expression of
certain variants results in inhibitory signaling through NKp44 and NKp30. Several
recent studies have found that the selective expression of some of these
inhibitory splice variants can significantly influence outcome in the contexts of
cancer, infection, and pregnancy. These findings establish that NCR functions are
more diverse than originally thought, and better understanding of their splice
variant expression profiles and ligand interactions are needed to establish their
functional regulation in the context of human health.
PMID- 28424699
TI - Patient's Experience in Pediatric Primary Immunodeficiency Disorders:
Computerized Classification of Questionnaires.
AB - INTRODUCTION: Primary immunodeficiency disorders (PIDs) are a heterogeneous group
of more than 200 rare diseases. Timely diagnosis is of uttermost importance.
Therefore, we aimed to develop a diagnostic questionnaire with computerized
pattern-recognition in order to support physicians to identify suspicious patient
histories. MATERIALS AND METHODS: Standardized interviews were conducted with
guardians of children with PID. The questionnaire based on parental observations
was developed using Colaizzis' framework for content analysis. Answers from 64
PID patients and 62 controls were analyzed by data mining methods in order to
make a diagnostic prediction. Performance was evaluated by k-fold stratified
cross-validation. RESULTS: The diagnostic support tool achieved a diagnostic
sensitivity of up to 98%. The analysis of 12 interviews revealed 26 main
phenomena observed by parents in the pre-diagnostic period. The questions were
systematically phrased and selected resulting in a 36-item questionnaire. This
was answered by 126 patients with or without PID to evaluate prediction. Item
analysis revealed significant questions. DISCUSSION: Our approach proved suitable
for recognizing patterns and thus differentiates between observations of PID
patients and control groups. These findings provide the basis for developing a
tool supporting physicians to consider a PID with a questionnaire. These data
support the notion that patient's experience is a cornerstone in the diagnostic
process.
PMID- 28424700
TI - Grand Challenges in Immunological Memory.
PMID- 28424701
TI - Clinical Overlapping in Autoinflammatory Diseases: The Role of Gene Duplication.
PMID- 28424704
TI - DRACO-STEM: An Automatic Tool to Generate High-Quality 3D Meshes of Shoot Apical
Meristem Tissue at Cell Resolution.
AB - Context: The shoot apical meristem (SAM), origin of all aerial organs of the
plant, is a restricted niche of stem cells whose growth is regulated by a complex
network of genetic, hormonal and mechanical interactions. Studying the
development of this area at cell level using 3D microscopy time-lapse imaging is
a newly emerging key to understand the processes controlling plant morphogenesis.
Computational models have been proposed to simulate those mechanisms, however
their validation on real-life data is an essential step that requires an adequate
representation of the growing tissue to be carried out. Achievements: The tool we
introduce is a two-stage computational pipeline that generates a complete 3D
triangular mesh of the tissue volume based on a segmented tissue image stack.
DRACO (Dual Reconstruction by Adjacency Complex Optimization) is designed to
retrieve the underlying 3D topological structure of the tissue and compute its
dual geometry, while STEM (SAM Tissue Enhanced Mesh) returns a faithful
triangular mesh optimized along several quality criteria (intrinsic quality,
tissue reconstruction, visual adequacy). Quantitative evaluation tools measuring
the performance of the method along those different dimensions are also provided.
The resulting meshes can be used as input and validation for biomechanical
simulations. Availability: DRACO-STEM is supplied as a package of the open-source
multi-platform plant modeling library OpenAlea (http://openalea.github.io/)
implemented in Python, and is freely distributed on GitHub
(https://github.com/VirtualPlants/draco-stem) along with guidelines for
installation and use.
PMID- 28424702
TI - Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance.
AB - Fas-mediated apoptosis contributes to physiological and pathological cellular
processes, such as differentiation and survival. In particular, the roles of Fas
in immune cells are complex and critical for the maintenance of immune tolerance.
The precise pathways and unique functions associated with Fas/FasL-mediated
signaling in the immune system are known. The dual character of Fas/FasL-mediated
immune regulation that induces beneficial or harmful effects is associated with
the onset or development of immune disorders. Studies on mutations in genes
encoding Fas and FasL gene of humans and mice contributed to our understanding of
the pathogenesis of autoimmune diseases. Here, we review the opposing functions
of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells,
and complex pathogenesis of autoimmunity mediated by Fas/FasL.
PMID- 28424705
TI - Contemporary Understanding of miRNA-Based Regulation of Secondary Metabolites
Biosynthesis in Plants.
AB - Plant's secondary metabolites such as flavonoids, terpenoids, and alkaloids etc.
are known for their role in the defense against various insects-pests of plants
and for medicinal benefits in human. Due to the immense biological importance of
these phytochemicals, understanding the regulation of their biosynthetic pathway
is crucial. In the recent past, advancement in the molecular technologies has
enabled us to better understand the proteins, enzymes, genes, etc. involved in
the biosynthetic pathway of the secondary metabolites. miRNAs are magical, tiny,
non-coding ribonucleotides that function as critical regulators of gene
expression in eukaryotes. Despite the accumulated knowledge of the miRNA-mediated
regulation of several processes, the involvement of miRNAs in regulating
secondary plant product biosynthesis is still poorly understood. Here, we
summarize the recent progress made in the area of identification and
characterizations of miRNAs involved in regulating the biosynthesis of secondary
metabolites in plants and discuss the future perspectives for designing the
viable strategies for their targeted manipulation.
PMID- 28424703
TI - Immune Responses to Bacillus Calmette-Guerin Vaccination: Why Do They Fail to
Protect against Mycobacterium tuberculosis?
AB - Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is
the current leading cause of death due to a single infectious organism. Although
curable, the broad emergence of multi-, extensive-, extreme-, and total-drug
resistant strains of M.tb has hindered eradication efforts of this pathogen.
Furthermore, computational models predict a quarter of the world's population is
infected with M.tb in a latent state, effectively serving as the largest
reservoir for any human pathogen with the ability to cause significant morbidity
and mortality. The World Health Organization has prioritized new strategies for
improved vaccination programs; however, the lack of understanding of
mycobacterial immunity has made it difficult to develop new successful vaccines.
Currently, Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only vaccine
approved for use to prevent TB. BCG is highly efficacious at preventing meningeal
and miliary TB, but is at best 60% effective against the development of pulmonary
TB in adults and wanes as we age. In this review, we provide a detailed summary
on the innate immune response of macrophages, dendritic cells, and neutrophils in
response to BCG vaccination. Additionally, we discuss adaptive immune responses
generated by BCG vaccination, emphasizing their specific contributions to
mycobacterial immunity. The success of future vaccines against TB will directly
depend on our understanding of mycobacterial immunity.
PMID- 28424706
TI - Evaluation of Yield and Drought Using Active and Passive Spectral Sensing Systems
at the Reproductive Stage in Wheat.
AB - Active and passive sensors are available for ground-based, high-throughput
phenotyping in the field. However, these sensor systems have seldom been compared
with respect to their determination of plant water status and water use
efficiency related parameters under drought conditions. In this study, five
passive and active reflectance sensors, including a hyperspectral passive sensor,
an active flash sensor (AFS), the Crop Circle, and the GreenSeeker, were
evaluated to assess drought-related destructive and non-destructive
morphophysiological parameters (ground cover, relative leaf water content, leaf
temperature, and carbon isotope discrimination of leaves and grain) and grain
yield of twenty wheat (Triticum aestivum L.) cultivars. Measurements were
conducted in a 2-year study, including a drought stress and a control environment
under field conditions. A comparison of the active sensors at the heading,
anthesis and grain-filling stages indicated that the Crop Circle provided the
most significant and robust relationships with drought-related parameters
(relative leaf water content and leaf and grain carbon isotope discrimination).
In comparison with the passive sensor, the five water and normalized water
indices (WI and NWI-1 to 4), which are only provided by the passive sensor,
showed the strongest relationships with the drought stress-related parameters (r
= -0.49 to -0.86) and grain yield (r = -0.88) at anthesis. This paper indicates
that precision phenotyping allows the integration of water indices in breeding
programs to rapidly and cost-effectively identify drought-tolerant genotypes.
This is supported by the fact that grain yield and the water indices showed the
same heritability under drought conditions.
PMID- 28424708
TI - Quantitative Trait Locus Mapping for Verticillium wilt Resistance in an Upland
Cotton Recombinant Inbred Line Using SNP-Based High Density Genetic Map.
AB - Verticillium wilt (VW) caused by Verticillium dahlia Kleb is one of the most
destructive diseases of cotton. Numerous efforts have been made to improve the
resistance of upland cotton against VW, with little progress achieved due to the
paucity of upland cotton breeding germplasms with high level of resistance to VW.
Gossypium barbadense was regarded as more resistant compared to upland cotton;
however, it is difficult to apply the resistance from G. barbadense to upland
cotton improvement because of the hybrid breakdown and the difficulty to fix
resistant phenotype in their interspecific filial. Here we reported QTLs related
to VW resistance identified in upland cotton based on 1 year experiment in
greenhouse with six replications and 4 years investigations in field with two
replications each year. In total, 119 QTLs of disease index (DI) and of disease
incidence (DInc) were identified on 25 chromosome of cotton genome except
chromosome 13 (c13). For DI, 62 QTLs explaining 3.7-12.2% of the observed
phenotypic variations were detected on 24 chromosomes except c11 and c13. For
DInc, 59 QTLs explaining 2.3-21.30% of the observed PV were identified on 19
chromosomes except c5, c8, c12-c13, c18-c19, and c26. Seven DI QTLs were detected
to be stable in at least environments, among which six have sGK9708 alleles,
while 28 DInc QTLs were detected to be stable in at least environments. Eighteen
QTL clusters containing 40 QTLs were identified on 13 chromosomes (c1-c4, c6-c7,
c10, c14, c17 c20-c22, and c24-c25). Most of the stable QTLs aggregated into
these clusters. These QTLs and clusters identification can be an important step
toward Verticillium wilt resistant gene cloning in upland cotton and provide
useful information to understand the complex genetic bases of Verticillium wilt
resistance.
PMID- 28424709
TI - Evolutionary Analysis of Snf1-Related Protein Kinase2 (SnRK2) and Calcium Sensor
(SCS) Gene Lineages, and Dimerization of Rice Homologs, Suggest Deep Biochemical
Conservation across Angiosperms.
AB - Members of the sucrose non-fermenting related kinase Group2 (SnRK2) subclasses
are implicated in both direct and indirect abscisic acid (ABA) response pathways.
We have used phylogenetic, biochemical, and transient in vivo approaches to
examine interactions between Triticum tauschii protein kinase 1 (TtPK1) and an
interacting protein, Oryza sativa SnRK2-calcium sensor (OsSCS1). Given that TtPK1
has 100% identity with its rice ortholog, osmotic stress/ABA-activated protein
kinase (OsSAPK2), we hypothesized that the SCS and TtPK1 interactions are present
in both wheat and rice. Here, we show that SnRK2s are clearly divided into four
pan-angiosperm clades with those in the traditionally defined Subclass II
encompassing two distinct clades (OsSAPK1/2 and OsSAPK3), although OsSAPK3 lacks
an Arabidopsis ortholog. We also show that SCSs are distinct from a second
lineage, that we term SCSsister, and while both clades pre-date land plants, the
SCSsister clade lacks Poales representatives. Our Y2H assays revealed that the
removal of the OsSCS1 C-terminal region along with its N-terminal EF-hand
abolished its interaction with the kinase. Using transient in planta bimolecular
fluorescence complementation experiments, we demonstrate that TtPK1/OsSCS1
dimerization co-localizes with DAPI-stained nuclei and with FM4-64-stained
membranes. Finally, OsSCS1- and OsSAPK2-hybridizing transcripts co-accumulate in
shoots/coleoptile of drying seedlings, consistent with up-regulated kinase
transcripts of PKABA1 and TtPK1. Our studies suggest that interactions between
homologs of the SnRK2 and SCS lineages are broadly conserved across angiosperms
and offer new directions for investigations of related proteins.
PMID- 28424707
TI - New Insights on Leucine-Rich Repeats Receptor-Like Kinase Orthologous
Relationships in Angiosperms.
AB - Leucine-Rich Repeats Receptor-Like Kinase (LRR-RLK) genes represent a large and
complex gene family in plants, mainly involved in development and stress
responses. These receptors are composed of an LRR-containing extracellular domain
(ECD), a transmembrane domain (TM) and an intracellular kinase domain (KD). To
provide new perspectives on functional analyses of these genes in model and non
model plant species, we performed a phylogenetic analysis on 8,360 LRR-RLK
receptors in 31 angiosperm genomes (8 monocots and 23 dicots). We identified 101
orthologous groups (OGs) of genes being conserved among almost all monocot and
dicot species analyzed. We observed that more than 10% of these OGs are absent in
the Brassicaceae species studied. We show that the ECD structural features are
not always conserved among orthologs, suggesting that functions may have diverged
in some OG sets. Moreover, we looked at targets of positive selection footprints
in 12 pairs of OGs and noticed that depending on the subgroups, positive
selection occurred more frequently either in the ECDs or in the KDs.
PMID- 28424710
TI - Identification and Characterization of microRNA319a and Its Putative Target Gene,
PvPCF5, in the Bioenergy Grass Switchgrass (Panicum virgatum).
AB - Due to its high biomass yield, low environmental impact, and widespread
adaptability to poor soils and harsh conditions, switchgrass (Panicum virgatum
L.), a warm-region perennial herbaceous plant, has attracted much attention in
recent years. However, little is known about microRNAs (miRNAs) and their
functions in this bioenergy grass. Here, we identified and characterized a miRNA
gene, Pvi-MIR319a, encoding microRNA319a in switchgrass. Transgenic rice lines
generated by overexpressing the Pvi-MIR319a precursor gene exhibited broader
leaves and delayed flowering compared with the control. Gene expression analysis
indicated at least four putative target genes were downregulated. Additionally,
we cloned a putative target gene (PvPCF5) of Pvi-MIR319a from switchgrass.
PvPCF5, a TCP transcription factor, is a nuclear-localized protein with
transactivation activity and control the development of leaf. Our results suggest
that Pvi-MIR319a and its target genes may be used as potential genetic regulators
for future switchgrass genetic improvement.
PMID- 28424711
TI - Genomic, Molecular Evolution, and Expression Analysis of Genes Encoding Putative
Classical AGPs, Lysine-Rich AGPs, and AG Peptides in Brassica rapa.
AB - Arabinogalactan proteins (AGPs) belong to a class of Pro/Hyp-rich glycoproteins
and are some of the most complex types of macromolecules found in plants. In the
economically important plant species, Brassica rapa, only chimeric AGPs have been
identified to date. This has significantly limited our understanding of the
functional roles of AGPs in this plant. In this study, 64 AGPs were identified in
the genome of B. rapa, including 33 classical AGPs, 28 AG peptides and three lys
rich AGPs. Syntenic gene analysis between B. rapa and A. thaliana suggested that
the whole genome triplication event dominated the expansion of the AGP gene
family in B. rapa. This resulted in a high retained proportion of the AGP family
in the B. rapa genome, especially in the least fractionated subgenome.
Phylogenetic and motif analysis classified the classical AGPs into six clades and
three orphan genes, and the AG peptides into three clades and five orphan genes.
Classical AGPs has a faster rate of molecular evolution than AG peptides revealed
by estimation of molecular evolution rates. However, no significant differences
were observed between classical AGPs and lys-rich AGPs. Under control conditions
and in response to phytohormones treatment, a complete expression profiling
experiment has identified five anther-specific AGPs and quite a number of AGPs
responding to abscisic acid, methyl jasmonate and/or gibberellin. In this study,
we presented a bioinformatics approach to identify important types of AGPs.
Moreover, the association between their function and their protein structure, as
well as the evolution and the expression of AGP genes were investigated, which
might provide fundamental information for revealing the roles of AGPs in B. rapa.
PMID- 28424713
TI - Comprehensive Genomic Identification and Expression Analysis of the Phosphate
Transporter (PHT) Gene Family in Apple.
AB - Elemental phosphorus (Pi) is essential to plant growth and development. The
family of phosphate transporters (PHTs) mediates the uptake and translocation of
Pi inside the plants. Members include five sub-cellular phosphate transporters
that play different roles in Pi uptake and transport. We searched the Genome
Database for Rosaceae and identified five clusters of phosphate transporters in
apple (Malus domestica), including 37 putative genes. The MdPHT1 family contains
14 genes while MdPHT2 has two, MdPHT3 has seven, MdPHT4 has 11, and MdPHT5 has
three. Our overview of this gene family focused on structure, chromosomal
distribution and localization, phylogenies, and motifs. These genes displayed
differential expression patterns in various tissues. For example, expression was
high for MdPHT1;12, MdPHT3;6, and MdPHT3;7 in the roots, and was also increased
in response to low-phosphorus conditions. In contrast, MdPHT4;1, MdPHT4;4, and
MdPHT4;10 were expressed only in the leaves while transcript levels of MdPHT1;4,
MdPHT1;12, and MdPHT5;3 were highest in flowers. In general, these 37 genes were
regulated significantly in either roots or leaves in response to the imposition
of phosphorus and/or drought stress. The results suggest that members of the PHT
family function in plant adaptations to adverse growing environments. Our study
will lay a foundation for better understanding the PHT family evolution and
exploring genes of interest for genetic improvement in apple.
PMID- 28424712
TI - A Functional Approach towards Understanding the Role of the Mitochondrial
Respiratory Chain in an Endomycorrhizal Symbiosis.
AB - Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able
to provide several ecosystem services for crop production. Current economic,
social and legislative contexts should drive the so-called "second green
revolution" by better exploiting these beneficial microorganisms. Many challenges
still need to be overcome to better understand the mycorrhizal symbiosis, among
which (i) the biotrophic nature of AMF, constraining their production, while (ii)
phosphate acts as a limiting factor for the optimal mycorrhizal inoculum
application and effectiveness. Organism fitness and adaptation to the changing
environment can be driven by the modulation of mitochondrial respiratory chain,
strongly connected to the phosphorus processing. Nevertheless, the role of the
respiratory function in mycorrhiza remains largely unexplored. We hypothesized
that the two mitochondrial respiratory chain components, alternative oxidase
(AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal
behavior. For this, a complex approach was developed. At the pre-symbiotic phase
(axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare
spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid
(SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid -
ABA and gibberellic acid - Ga3). At the symbiotic phase, we analyzed phenotypic
and transcriptomic (genes involved in respiration, transport, and fermentation)
responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse
conditions): we monitored the effects driven by ABA, and explored the modulations
induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM
inhibited in vitro spore germination while ABA and Ga3 induced differential spore
germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong
arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA
treated plants, R. irregulare induced down-regulation of StAOX gene isoforms and
up-regulation of genes involved in plant COX pathway. In all phosphorus (P)
concentrations, blocking AOX or COX induced opposite mycorrhizal patterns in
planta: KCN induced higher Arum-type arbuscule density, positive MGD but lower
root colonization compared to SHAM, which favored Paris-type formation and
negative MGD. Following our results and current state-of-the-art knowledge, we
discuss metabolic functions linked to respiration that may occur within
mycorrhizal behavior. We highlight potential connections between AOX pathways and
fermentation, and we propose new research and mycorrhizal application
perspectives.
PMID- 28424714
TI - Relationships between Root Pathogen Resistance, Abundance and Expression of
Pseudomonas Antimicrobial Genes, and Soil Properties in Representative Swiss
Agricultural Soils.
AB - Strains of Pseudomonas that produce antimicrobial metabolites and control
soilborne plant diseases have often been isolated from soils defined as disease
suppressive, i.e., soils, in which specific plant pathogens are present, but
plants show no or reduced disease symptoms. Moreover, it is assumed that
pseudomonads producing antimicrobial compounds such as 2,4-diacetylphloroglucinol
(DAPG) or phenazines (PHZ) contribute to the specific disease resistance of
suppressive soils. However, pseudomonads producing antimicrobial metabolites are
also present in soils that are conducive to disease. Currently, it is still
unknown whether and to which extent the abundance of antimicrobials-producing
pseudomonads is related to the general disease resistance of common agricultural
soils. Moreover, virtually nothing is known about the conditions under which
pseudomonads express antimicrobial genes in agricultural field soils. We present
here results of the first side-by-side comparison of 10 representative Swiss
agricultural soils with a cereal-oriented cropping history for (i) the resistance
against two soilborne pathogens, (ii) the abundance of Pseudomonas bacteria
harboring genes involved in the biosynthesis of the antimicrobials DAPG, PHZ, and
pyrrolnitrin on roots of wheat, and (iii) the ability to support the expression
of these genes on the roots. Our study revealed that the level of soil disease
resistance strongly depends on the type of pathogen, e.g., soils that are highly
resistant to Gaeumannomyces tritici often are highly susceptible to Pythium
ultimum and vice versa. There was no significant correlation between the disease
resistance of the soils, the abundance of Pseudomonas bacteria carrying DAPG,
PHZ, and pyrrolnitrin biosynthetic genes, and the ability of the soils to support
the expression of the antimicrobial genes. Correlation analyses indicated that
certain soil factors such as silt, clay, and some macro- and micronutrients
influence both the abundance and the expression of the antimicrobial genes. Taken
together, the results of this study suggests that pseudomonads producing DAPG,
PHZ, or pyrrolnitrin are present and abundant in Swiss agricultural soils and
that the soils support the expression of the respective biosynthetic genes in
these bacteria to various degrees. The precise role that these pseudomonads play
in the general disease resistance of the investigated agricultural soils remains
elusive.
PMID- 28424715
TI - Temporal Petal Closure Benefits Reproductive Development of Magnolia denudata
(Magnoliaceae) in Early Spring.
AB - The Magnoliaceae shows strong phylogenetic niche conservatism, in which temporal
petal closure has been extensively reported. However, it is yet elusive whether
temporal petal closure is an idle floral character inherited from their ancestors
or an adaptive trait to their habitats. Here, we monitored the process of
temporal floral closure and re-opening in a thermogenic plant, Magnolia denudata
(Magnoliaceae). Furthermore, we artificially interrupted temporal petal closure
and investigated its effects on development of female and male gametophytes.
Intriguingly, we found considerable anatomical changes in the anthers shortly
after temporal closure of petals: disintegration of tapeta, crack of anther
walls, and release of matured pollens. In comparison with normal flowers,
artificially interrupted flowers (no petal closure) showed delayed anther
development and slower pollen germination on stigmas, while little difference in
embryo morphology was observed during the early stage of embryo development.
Moreover, seed set and quality were significantly decreased when petal closure
was prevented. In addition, we found pollination accelerated floral closure in M.
denudata. Taken together, temporal floral closure benefits reproduction of M.
denudata in early spring by promoting anther development and pollen function,
which suggests that it is an adaptive floral trait to its specific habitat.
PMID- 28424716
TI - Growth Stimulatory Effects and Genome-Wide Transcriptional Changes Produced by
Protein Hydrolysates in Maize Seedlings.
AB - Protein hydrolysates are an emerging class of crop management products utilized
for improving nutrient assimilation and mitigating crop stress. They generally
consist of a mixture of peptides and free amino acids derived from the hydrolysis
of plant or animal sources. The present work was aimed at studying the effects
and the action mechanisms of a protein hydrolysate derived from animal residues
on maize root growth and physiology in comparison with the effects induced by
either free amino acids or inorganic N supply. The application of the protein
hydrolysate caused a remarkable enhancement of root growth. In particular, in the
protein hydrolysate-treated plants the length and surface area of lateral roots
were about 7 and 1.5 times higher than in plants treated with inorganic N or free
amino acids, respectively. The root growth promoting effect of the protein
hydrolysate was associated with an increased root accumulation of K, Zn, Cu, and
Mn when compared with inorganic N and amino acids treatments. A microarray
analysis allowed to dissect the transcriptional changes induced by the different
treatments demonstrating treatment-specific effects principally on cell wall
organization, transport processes, stress responses and hormone metabolism.
PMID- 28424717
TI - Expression of the Maize Dof1 Transcription Factor in Wheat and Sorghum.
AB - Nitrogen is essential for plant growth and development. Improving the ability of
plants to acquire and assimilate nitrogen more efficiently is a key agronomic
parameter that will augment sustainability in agriculture. A transcription factor
approach was pursued to address improvement of nitrogen use efficiency in two
major commodity crops. To this end, the Zea mays Dof1 (ZmDof1) transcription
factor was expressed in both wheat (Triticum aestivum) and sorghum (Sorghum
bicolor) either constitutively, UBI4 promoter from sugarcane, or in a tissue
specific fashion via the maize rbcS1 promoter. The primary transcription
activation target of ZmDof1, phosphoenolpyruvate carboxylase (PEPC), is observed
in transgenic wheat events. Expression ZmDof1 under control of the rbcs1 promoter
translates to increase in biomass and yield components in wheat. However,
constitutive expression of ZmDof1 led to the down-regulation of genes involved in
photosynthesis and the functional apparatus of chloroplasts, and an outcome that
negatively impacts photosynthesis, height, and biomass in wheat. Similar patterns
were also observed in sorghum transgenic events harboring the constitutive
expression cassette of ZmDof1. These results indicate that transcription factor
strategies to boost agronomic phenotypic outcomes in crops need to consider
expression patterns of the genetic elements to be introduced.
PMID- 28424718
TI - Comparative Performance of Multivariable Agro-Physiological Parameters for
Detecting Salt Tolerance of Wheat Cultivars under Simulated Saline Field Growing
Conditions.
AB - Field-based trials are crucial for successfully achieving the goals of plant
breeding programs aiming to screen and improve the salt tolerance of crop
genotypes. In this study, simulated saline field growing conditions were designed
using the subsurface water retention technique (SWRT) and three saline irrigation
levels (control, 60, and 120 mM NaCl) to accurately appraise the suitability of a
set of agro-physiological parameters including shoot biomass, grain yield, leaf
water relations, gas exchange, chlorophyll fluorescence, and ion accumulation as
screening criteria to establish the salt tolerance of the salt-tolerant (Sakha
93) and salt-sensitive (Sakha 61) wheat cultivars. Shoot dry weight and grain
yield per hectare were substantially reduced by salinity, but the reduction was
more pronounced in Sakha 61 than in Sakha 93. Increasing salinity stress caused a
significant decrease in the net photosynthesis rate and stomatal conductance of
both cultivars, although their leaf turgor pressure increased. The accumulation
of toxic ions (Na+ and Cl-) was higher in Sakha 61, but the accumulation of
essential cations (K+ and Ca2+) was higher in Sakha 93, which could be the reason
for the observed maintenance of the higher leaf turgor of both cultivars in the
salt treatments. The maximum quantum PSII photochemical efficiency (Fv/Fm) and
the PSII quantum yield (PhiPSII) decreased with increasing salinity levels in
Sakha 61, but they only started to decline at the moderate salinity condition in
Sakha 93. The principle component analysis successfully identified the
interrelationships between all parameters. The parameters of leaf water relations
and toxic ion concentrations were significantly related to each other and could
identify Sakha 61 at mild and moderate salinity levels, and, to a lesser extent,
Sakha 93 at the moderate salinity level. Both cultivars under the control
treatment and Sakha 93 at the mild salinity level were identified by most of the
other parameters. The variability in the angle between the vectors of parameters
explained which parameters could be used as individual, interchangeable, or
supplementary screening criteria for evaluating wheat salt tolerance under
simulated field conditions.
PMID- 28424719
TI - Comparative Analysis of Root Traits and the Associated QTLs for Maize Seedlings
Grown in Paper Roll, Hydroponics and Vermiculite Culture System.
AB - Root system architecture (RSA) plays an important role in the acquisition of both
nitrogen (N) and phosphorus (P) from the environment. Currently RSA is rarely
considered as criteria for selection to improve nutrient uptake efficiency in
crop breeding. Under field conditions roots can be greatly influenced by
uncontrolled environment factors. Therefore, it is necessary to develop fast
selection methods for evaluating root traits of young seedlings in the lab which
can then be related to high nutrient efficiency of adult plants in the field.
Here, a maize recombination inbred line (RILs) population was used to compare the
genetic relationship between RSA and nitrogen and phosphorous efficiency traits.
The phenotypes of eight RSA-related traits were evaluated in young seedlings
using three different growth systems (i.e., paper roll, hydroponics and
vermiculite), and then subjected to correlation analysis with N efficiency and P
efficiency related traits measured under field conditions. Quantitative trait
loci (QTL) of RSA were determined and QTL co-localizations across different
growth systems were further analyzed. Phenotypic associations were observed for
most of RSA traits among all three culture systems. RSA-related traits in
hydroponics and vermiculite weakly correlated with Nitrogen (NupE) uptake
efficiency (r = 0.17-0.31) and Phosphorus (PupE) uptake efficiency (r = 0.22
0.34). This correlation was not found in the paper roll growth system. A total of
14 QTLs for RSA were identified in paper rolls, 18 in hydroponics, and 14 in
vermiculite. Co-localization of QTLs for RSA traits were identified in six
chromosome regions of bin 1.04/1.05, 1.06, 2.04/2.05, 3.04, 4.05, and 5.04/5.05.
The results suggest the problem of using the phenotype from one growth system to
predict those in another growth system. Assessing RSA traits at the seedling
stage using either hydroponics or a vermiculite system appears better suited than
the paper roll system as an important index to accelerate the selection of high N
and P efficient genotypes for maize breeding programs.
PMID- 28424720
TI - Arbuscular Mycorrhizal Fungus Rhizophagus irregularis Increased Potassium Content
and Expression of Genes Encoding Potassium Channels in Lycium barbarum.
AB - Potassium in plants accounts for up to 10% dry weight, and participates in
different physiological processes. Under drought stress, plant requires more
potassium but potassium availability in soil solutes is lowered by decreased soil
water content. Forming symbiosis with arbuscular mycorrhizal (AM) fungi not only
enlarges exploration range of plant for mineral nutrients and water in soil, but
also improves plant drought tolerance. However, the regulation of AM fungi on
plant root potassium uptake and translocation from root to shoot was less
reported. In current study, the effect of an AM fungus (Rhizophagus irregularis),
potassium application (0, 2, and 8 mM), and drought stress (30% field capacity)
on Lycium barbarum growth and potassium status was analyzed. Ten weeks after
inoculation, R. irregularis colonized more than 58% roots of L. barbarum
seedlings, and increased plant growth as well as potassium content. Potassium
application increased colonization rate of R. irregularis, plant growth,
potassium content, and decreased root/shoot ratio. Drought stress increased
colonization rate of R. irregularis and potassium content. Expression of two
putative potassium channel genes in root, LbKT1 and LbSKOR, was positively
correlated with potassium content in root and leaves, as well as the colonization
rate of R. irregularis. The increased L. barbarum growth, potassium content and
genes expression, especially under drought stress, suggested that R. irregularis
could improve potassium uptake of L. barbarum root and translocation from root to
shoot. Whether AM fungi could form a specific mycorrhizal pathway for plant
potassium uptake deserves further studies.
PMID- 28424721
TI - miRNA and Degradome Sequencing Reveal miRNA and Their Target Genes That May
Mediate Shoot Growth in Spur Type Mutant "Yanfu 6".
AB - The spur-type growth habit in apple trees is characterized by short internodes,
increased number of fruiting spurs, and compact growth that promotes flowering
and facilitates management practices, such as pruning. The molecular mechanisms
responsible for regulating spur-type growth have not been elucidated. In the
present study, miRNAs and the expression of their potential target genes were
evaluated in shoot tips of "Nagafu 2" (CF) and spur-type bud mutation "Yanfu 6"
(YF). A total of 700 mature miRNAs were identified, including 202 known apple
miRNAs and 498 potential novel miRNA candidates. A comparison of miRNA expression
in CF and YF revealed 135 differentially expressed genes, most of which were
downregulated in YF. YF also had lower levels of GA, ZR, IAA, and ABA hormones,
relative to CF. Exogenous applications of GA promoted YF shoot growth. Based on
the obtained results, a regulatory network involving plant hormones, miRNA, and
their potential target genes is proposed for the molecular mechanism regulating
the growth of YF. miRNA164, miRNA166, miRNA171, and their potential targets, and
associated plant hormones, appear to regulate shoot apical meristem (SAM) growth.
miRNA159, miRNA167, miRNA396, and their potential targets, and associated plant
hormones appear to regulate cell division and internode length. This study
provides a foundation for further studies designed to elucidate the mechanism
underlying spur-type apple architecture.
PMID- 28424722
TI - The Role of Auxin-Ethylene Crosstalk in Orchestrating Primary Root Elongation in
Sugar Beet.
AB - It is well-established in Arabidopsis and other species that ethylene inhibits
root elongation through the action of auxin. In sugar beet (Beta vulgaris L.)
ethylene promotes root elongation in a concentration dependent manner. However,
the crosstalk between ethylene and auxin remains unknown during sugar beet
seedling development. Our experiments have shown that exogenously applied auxin
(indole-3-acetic acid; IAA) also stimulates root elongation. We also show that
auxin promotes ethylene biosynthesis leading to longer roots. We have further
demonstrated that the auxin treatment stimulates ethylene production by
redirecting the pool of available 1-aminocyclopropane-1-carboxylic acid (ACC)
toward ethylene instead of malonyl-ACC (MACC) resulting in a prolonged period of
high rates of ethylene production and subsequently a longer root. On the other
hand we have also shown that endogenous IAA levels were not affected by an ACC
treatment during germination. All together our findings suggest that the general
model for auxin-ethylene crosstalk during early root development, where ethylene
controls auxin biosynthesis and transport, does not occur in sugar beet. On the
contrary, we have shown that the opposite, where auxin stimulates ethylene
biosynthesis, is true for sugar beet root development.
PMID- 28424723
TI - Evidence, Mechanism and Alternative Chemical Seedbank-Level Control of Glyphosate
Resistance of a Rigid Ryegrass (Lolium rigidum) Biotype from Southern Spain.
AB - Rigid ryegrass (Lolium rigidum) is one of the most troublesome weeds in different
crops in the Mediterranean region. A rigid ryegrass biotype from an olive grove
in Jaen province (Andalusia, southern Spain), potentially resistant to glyphosate
(RG), was tested for its resistance level through dose-response assays using a
susceptible biotype (SG). To test the hypothesis of a non-target-site-based
resistance, as point mutations are far less common mechanisms of glyphosate
resistance, studies were also conducted to elucidate whether resistance was
associated with biochemical, metabolism, molecular and/or physiological
mechanisms. Alternative herbicide-based control options, including single
herbicide or herbicide mixtures with glyphosate, applied at seedling, tillering
or full heading stages, were tested in field experiments for 2 years for their
efficacy against rigid ryegrass plants and their effects on the soil seed bank.
Resistance levels of the RG biotype were 23- (LD50) and 7-fold (GR50) higher
compared to the SG biotype. The SG biotype exhibited a significantly greater
shikimic acid accumulation than the RG one. At 96 HAT, 58 and 89% of applied 14C
glyphosate was up taken by leaves of RG and SG biotype plants, respectively, and,
at this time, a significantly higher proportion of the glyphosate taken up by the
treated leaf remained in its tissue in RG plants compared to the SG ones. The RG
biotype did not reveal any point mutation in the glyphosate target site EPSP
synthase. Overall, results confirmed reduced glyphosate uptake and translocation
as being the mechanism involved in glyphosate resistance in the RG biotype. RG
biotype responses to the alternative treatments tested in situ indicated that
herbicide applications at the later growth stage tended to be less effective in
terms of immediate effects on population size than earlier applications, and that
only in some cases, the removal of at least 85% of the RG biotype was achieved.
However, with few exceptions, the alternative treatments tested appeared to be
highly effective in reducing the seed bank irrespective of the growth stage. The
frequency of the resistant phenotype in the progeny of surviving plants of the RG
biotype was dependent on treatment. Results suggest that a potential exists for
effective management of glyphosate-resistant rigid ryegrass in olive groves in
southern Spain.
PMID- 28424724
TI - Soluble Starch Synthase III-1 in Amylopectin Metabolism of Banana Fruit:
Characterization, Expression, Enzyme Activity, and Functional Analyses.
AB - Soluble starch synthase (SS) is one of the key enzymes involved in amylopectin
biosynthesis in plants. However, no information is currently available about this
gene family in the important fruit crop banana. Herein, we characterized the
function of MaSSIII-1 in amylopectin metabolism of banana fruit and described the
putative role of the other MaSS family members. Firstly, starch granules, starch
and amylopectin content were found to increase during banana fruit development,
but decline during storage. The SS activity started to increase later than
amylopectin and starch content. Secondly, four putative SS genes were cloned and
characterized from banana fruit. Among them, MaSSIII-1 showed the highest
expression in banana pulp during fruit development at transcriptional levels.
Further Western blot analysis suggested that the protein was gradually increased
during banana fruit development, but drastically reduced during storage. This
expression pattern was highly consistent with changes in starch granules,
amylopectin content, and SS activity at the late phase of banana fruit
development. Lastly, overexpression of MaSSIII-1 in tomato plants distinctly
changed the morphology of starch granules and significantly increased the total
starch accumulation, amylopectin content, and SS activity at mature-green stage
in comparison to wild-type. The findings demonstrated that MaSSIII-1 is a key
gene expressed in banana fruit and responsible for the active amylopectin
biosynthesis, this is the first report in a fresh fruit species. Such a finding
may enable the development of molecular markers for banana breeding and genetic
improvement of nutritional value and functional properties of banana fruit.
PMID- 28424726
TI - Size-Mediated Interaction between a Cushion Species and Other Non-cushion Species
at High Elevations of the Hengduan Mountains, SW China.
AB - Arenaria polytrichoides (Caryophyllaceae) is a common cushion plant occurring at
high elevations in the Himalaya-Hengduan Mountains, SW China. It frequently has
other non-cushion species growing within its canopy, forming a contrast with the
surrounding areas because it creates patches of higher diversity and greater
biomass. In this study, we examined the relationship between the cushions and
associated non-cushion species along a gradient of cushion size. A total of 200
A. polytrichoides individuals were selected to fit four size classes. Field
measurements were carried out to assess canopy structure, functional traits
relevant to growth and reproduction, and soil quality below cushions along the
size gradient. Furthermore, the size effect of cushions on the richness and
abundance of species and biomass production was also examined. All the
morphological variables examined exhibited a positive correlation with cushion
size, as did the nutrients under cushions. Large and compact cushions were
associated with higher soil nutrient contents compared with small and loose
cushions. As a result of these biogenic environmental changes, there was a
stronger facilitation effect performed by large cushions. Data pertaining to
functional traits revealed that large cushions benefit from the enhanced
resources within their compact structure and exhibit greater fitness and a higher
reproductive output than small cushions. Our data indicated that interactions
occur between cushion species and other plants depending on the size of the
cushions, probably because of the greater heterogeneity of conditions beneath
larger cushions. These findings provide a clear demonstration of the generally
overlooked importance of the traits of nurse plants, such as size and age, in
terms of their facilitative effects.
PMID- 28424725
TI - A Genome-Scale Analysis of the PIN Gene Family Reveals Its Functions in Cotton
Fiber Development.
AB - The PIN-FORMED (PIN) protein, the most important polar auxin transporter, plays a
critical role in the distribution of auxin and controls multiple biological
processes. However, characterizations and functions of this gene family have not
been identified in cotton. Here, we identified the PIN family in Gossypium
hirsutum, Gossypium arboreum, and Gossypium raimondii. This gene family was
divided into seven subgroups. A chromosomal distribution analysis showed that
GhPIN genes were evenly distributed in eight chromosomes and that the whole
genome and dispersed duplications were the main duplication events for GhPIN
expansion. qRT-PCR analysis showed a tissue-specific expression pattern for
GhPIN. Likely due to the cis-element variations in their promoters, transcripts
of PIN6 and PIN8 genes from the At (tetraploid genome orginated from G. arboreum)
subgenome and PIN1a from the Dt (tetraploid genome orginated from G. raimondii)
subgenome in G. hirsutum was significantly increased compared to the transcripts
in the diploids. The differential regulation of these PIN genes after the
polyploidization may be conducive to fiber initiation and elongation. Exogenously
applied auxin polar transport inhibitor significantly suppressed fiber growth,
which is consistent with the essential function of these PIN genes for regulating
cotton fiber development. Furthermore, the overexpression of GhPIN1a_Dt,
GhPIN6_At, and GhPIN8_At in Arabidopsis promoted the density and length of
trichomes in leaves.
PMID- 28424727
TI - Host-Induced Silencing of Two Pharyngeal Gland Genes Conferred Transcriptional
Alteration of Cell Wall-Modifying Enzymes of Meloidogyne incognita vis-a-vis
Perturbed Nematode Infectivity in Eggplant.
AB - The complex parasitic strategy of Meloidogyne incognita appears to involve
simultaneous expression of its pharyngeal gland-specific effector genes in order
to colonize the host plants. Research reports related to effector crosstalk in
phytonematodes for successful parasitism of the host tissue is yet underexplored.
In view of this, we have used in planta effector screening approach to understand
the possible interaction of pioneer genes (msp-18 and msp-20, putatively involved
in late and early stage of M. incognita parasitism, respectively) with other
unrelated effectors such as cell-wall modifying enzymes (CWMEs) in M. incognita.
Host-induced gene silencing (HIGS) strategy was used to generate the transgenic
eggplants expressing msp-18 and msp-20, independently. Putative transformants
were characterized via qRT-PCR and Southern hybridization assay. SiRNAs specific
to msp-18 and msp-20 were also detected in the transformants via Northern
hybridization assay. Transgenic expression of the RNAi constructs of msp-18 and
msp-20 genes resulted in 43.64-69.68% and 41.74-67.30% reduction in M. incognita
multiplication encompassing 6 and 10 events, respectively. Additionally,
transcriptional oscillation of CWMEs documented in the penetrating and developing
nematodes suggested the possible interaction among CWMEs and pioneer genes. The
rapid assimilation of plant-derived carbon by invading nematodes was also
demonstrated using 14C isotope probing approach. Our data suggests that HIGS of
msp-18 and msp-20, improves nematode resistance in eggplant by affecting the
steady-state transcription level of CWME genes in invading nematodes, and
safeguard the plant against nematode invasion at very early stage because
nematodes may become the recipient of bioactive RNA species during the process of
penetration into the plant root.
PMID- 28424728
TI - Landscape Population Genomics of Forsythia (Forsythia suspensa) Reveal That
Ecological Habitats Determine the Adaptive Evolution of Species.
AB - Understanding the genetic mechanisms of adaptation to environmental variables is
a key concern in molecular ecology and evolutionary biology. Determining the
adaptive evolutionary direction and evaluating the adaptation status of species
can improve our understanding of these mechanisms. In this study, we sampled 20
populations of Forsythia suspensa to infer the relationship between environmental
variables and adaptive genetic variations. Population structure analysis revealed
that four genetic groups of F. suspensa exist resulting from divergent selection
driven by seven environmental variables. A total of 26 outlier loci were
identified by both BayeScan and FDIST2, 23 of which were environment-associated
loci (EAL). Environmental association analysis revealed that the environmental
variables related to the ecological habitats of F. suspensa are associated with
high numbers of EAL. Results of EAL characterization in F. suspensa are
consistent with the hypothesis that ecological habitats determine the adaptive
evolution of this species. Moreover, a model of species adaptation to
environmental variables was proposed in this study. The adaptation model was used
to further evaluate the adaptation status of F. suspensa to environmental
variables. This study will be useful to help us in understanding the adaptive
evolution of species in regions lacking strong selection pressure.
PMID- 28424729
TI - Genome-Wide Identification and Analyses of Calmodulins and Calmodulin-like
Proteins in Lotus japonicas.
AB - L. japonicus, a model plant of legumes plants, is widely used in symbiotic
nitrogen fixation. A large number of studies on it have been published based on
the genetic, biochemical, structural studies. These results are secondhand
reports that CaM is a key regulator during Rhizobial infection. In plants, there
are multiple CaM genes encoding several CaM isoforms with only minor amino acid
differences. Moreover, the regulation mechanism of this family of proteins during
rhizobia infection is still unclear. In the current study, a family of genes
encoding CaMs and CMLs that possess only the Ca2+-binding EF-hand motifs were
analyzed. Using ML and BI tree based on amino acid sequence similarity, seven
loci defined as CaMs and 19 CMLs, with at least 23% identity to CaM, were
identified. The phylogenetics, gene structures, EF hand motif organization, and
expression characteristics were evaluated. Seven CaM genes, encoding only 4
isoforms, were found in L. japonicus. According to qRT-PCR, four LjCaM isoforms
are involved in different rhizobia infection stages. LjCaM1 might be involved in
the early rhizobia infection epidermal cells stage. Furthermore, additional
structural differences and expression behaviors indicated that LjCMLs may have
different potential functions from LjCaMs.
PMID- 28424730
TI - Melatonin Improves Waterlogging Tolerance of Malus baccata (Linn.) Borkh.
Seedlings by Maintaining Aerobic Respiration, Photosynthesis and ROS Migration.
AB - Waterlogging, one of the notorious abiotic stressors, retards the growth of apple
plants and reduces their production. Thus, it is an urgent agenda for scientists
to identify the suitable remedies for this problem. In the current study, we
found that melatonin significantly improved the tolerance of apple seedlings
against waterlogging stress. This was indicated by the reduced chlorosis and
wilting of the seedlings after melatonin applications either by leaf spray or
root irrigation. The mechanisms involve in that melatonin functions to maintain
aerobic respiration, preserves photosynthesis and reduces oxidative damage of the
plants which are under waterlogging stress. Melatonin application also enhances
the gene expression of its synthetic enzymes (MbT5H1, MbAANAT3, MbASMT9) and
increases melatonin production. This is the first report of a positive feedback
that exogenous melatonin application promotes the melatonin synthesis in plants.
A post-transcriptional regulation apparently participated in this regulation.
When exogenous melatonin meets the requirement of the plants it is found that the
protein synthesis of MbASMT9 was suppressed. Taken together, the results showed
that melatonin was an effective molecule to protect plant, particularly apple
plant, against waterlogging stress.
PMID- 28424731
TI - Identification of TIFY Family Genes and Analysis of Their Expression Profiles in
Response to Phytohormone Treatments and Melampsora larici-populina Infection in
Poplar.
AB - The TIFY domain contains approximately 36 conserved amino acids that form the
core motif TIF[F/Y]XG, and they were reported to play important roles in plant
growth, tissue development and defense regulation. Moreover, more and more
evidence has shown that some members of the TIFY gene family perform their
functions by modulating plant hormone signaling pathways. Poplar trees are found
worldwide, and they comprise approximately 30 species. Benefit from the
importance of poplar and its advanced platform, this tree is considered to be the
model perennial plant. Here, we conducted a genome-wide identification of TIFY
genes in poplar, and 24 TIFY genes were found. These 24 TIFY genes were assigned
to different subfamilies according to the presence or absence of domains and
motifs that they harbored. Careful analyses of their locations, structures,
evolution and duplication patterns revealed an overview of this gene family in
poplar. The expression profiles of these 24 TIFY genes were then analyzed in
different tissues using publicly available expression data; their expression
profiles following different JA/SA treatments and infection with leaf rust
pathogen were also carefully examined by qRT-PCR assays. Based on their
expression profiles, the functions of a number of TIFY genes could be predicted.
By performing this study, we have provided valuable information for further
functional characterisation of TIFY genes in poplar and candidate genes for the
improvement of poplar disease resistance.
PMID- 28424732
TI - Evidence for Loss in Identity, De-Differentiation, and Trans-Differentiation of
Islet beta-Cells in Type 2 Diabetes.
AB - The two main types of diabetes mellitus have distinct etiologies, yet a similar
outcome: loss of islet beta-cell function that is solely responsible for the
secretion of the insulin hormone to reduce elevated plasma glucose toward
euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by
autoimmune-mediated beta-cell death leading to insulin-dependence, whereas type 2
diabetes (T2D) has hallmarks of peripheral insulin resistance, beta-cell
dysfunction, and cell death. However, a growing body of evidence suggests that,
especially during T2D, key components of beta-cell failure involves: (1) loss of
cell identity, specifically proteins associated with mature cell function (e.g.,
insulin and transcription factors like MAFA, PDX1, and NKX6.1), as well as (2) de
differentiation, defined by regression to a progenitor or stem cell-like state.
New technologies have allowed the field to compare islet cell characteristics
from normal human donors to those under pathophysiological conditions by single
cell RNA-Sequencing and through epigenetic analysis. This has revealed a
remarkable level of heterogeneity among histologically defined "insulin-positive"
beta-cells. These results not only suggest that these beta-cell subsets have
different responses to insulin secretagogues, but that defining their unique gene
expression and epigenetic modification profiles will offer opportunities to
develop cellular therapeutics to enrich/maintain certain subsets for correcting
pathological glucose levels. In this review, we will summarize the recent
literature describing how beta-cell heterogeneity and plasticity may be
influenced in T2D, and various possible avenues of therapeutic intervention.
PMID- 28424734
TI - Influence of Teeth Preparation Finishing on the Adaptation of Lithium Disilicate
Crowns.
AB - The polishing step of teeth preparations for crowns is a step often performed, so
that there is an increased time during the clinical procedure. The aim of this
study is to evaluate the marginal and internal adaptation of all-ceramic CAD/CAM
lithium disilicate crowns in polished preparations for crown and nonpolished
preparations for crowns. For this purpose, 20 first molars were selected, which
were divided into two groups (n = 10) G1, teeth that received surface roughening
similar to preparation without polishing, and G2 (control), polished
preparations. After the preparations were completed the teeth were scanned (Cerec
Bluecam, Sirona, Bensheim, Germany), and the crowns were designed and machined
using CAD/CAM technology (Sirona, Bensheim, Germany). The adaptation of the
pieces was evaluated using polyvinyl siloxane replicas and stereomicroscope
photographs with 70x magnifications. The normality test indicated a nonnormal
result, so a Man-Whitney nonparametric test was performed. One out of the 24
measured regions showed a statistically significant difference (p = 0.0494). With
this study it can be concluded that crowns fabricated by CAD/CAM technology
performed on unpolished preparations are not influenced by the internal marginal
adaptation and the ceramic part and are different from polished preparations.
PMID- 28424733
TI - Combined Implant and Tooth Support: An Up-to-Date Comprehensive Overview.
AB - Objectives. This article presents a review on the concerned topics and some
considerations related to the concept of splinting teeth and implants in the
rehabilitation of partial edentulism. Study Selection. An electronic
PubMed/MEDLINE and manual search of identified articles and reviews as well as
clinical, laboratory, and finite element studies was performed in this project.
Due to the shortage in within-subject, long term, randomized, controlled clinical
trials regarding the subject a meta-analysis was not possible. Results. Although
surrounded with some controversy, joining teeth and implants during the
rehabilitation of partial edentulism provides the clinicians with more treatment
options where proprioception and bone volume are maintained and distal
cantilevers and free end saddles are eliminated. It makes the treatment less
complex, of less cost, and more acceptable for the patient. Conclusions. Whenever
suitable and justified, combining implant and tooth support might be recommended
as an alternative during rehabilitation of partial edentulism. Based on the
literature, clinical tips and suggestions were recommended to increase the
success of this treatment.
PMID- 28424735
TI - Tongue Necrosis Secondary to Giant Cell Arteritis: A Case Report and Literature
Review.
AB - Giant cell arteritis is a form of vasculitis involving the medium- and large
sized arteries that chiefly affects older people. Clinical findings are headache,
jaw claudication, fever, pain, and thickening of the temporal artery. The most
feared complication is visual loss due to impairment of the ophthalmic artery and
posterior ciliary arteries. This a case report of an 85-year-old male presenting
with headache and jaw pain, who was admitted with tongue necrosis as an initial
manifestation of giant cell arteritis. The necrotic area detached spontaneously
after two weeks of therapy with corticosteroids and methotrexate. Reviewing the
literature, our patient presented with clinical symptoms consistent with most
reports, except for the fact of being male. Although unusual as an initial
manifestation, tongue necrosis is an important alert for diagnosing giant cell
arteritis. Early diagnosis and treatment of this atypical manifestation may
reduce morbidity.
PMID- 28424736
TI - A Case of Xanthogranulomatous Pyelonephritis Associated with Renoduodenal
Fistula.
AB - Xanthogranulomatous pyelonephritis (XGP) is a rare form of pyelonephritis
associated with repeated infection, chronic inflammation, and obstruction.
Various fistulas, including those to the intestine, are a known association with
XGP. Here, a 55-year-old woman with a history of multiple previous renal calculi
presented with dysuria and back pain. Contrast-enhanced computed tomography (CT)
revealed a soft tissue density in her renal pelvis and perirenal space consistent
with XGP along with a tract connecting the upper pole of her right kidney to the
second portion of the duodenum. This finding was subsequently confirmed during
percutaneous nephrostomy placement, stent placement, a small bowel follow-through
study, and upper endoscopy. She was diagnosed with XGP with associated
renoduodenal fistula, eventually treated by open nephrectomy with fistula
takedown. Histopathologic analysis was consistent with the diagnosis of XGP with
no malignant or infectious cause of the fistula. XGP should be considered in the
diagnosis of patients with dysuria and back pain, especially when a history of
obstruction or chronic inflammation. Associated fistulas should also be
considered prior to surgical management to prevent complications.
PMID- 28424737
TI - GC-MS Based Metabolite Profiling, Antioxidant and Antimicrobial Properties of
Different Solvent Extracts of Malaysian Plectranthus amboinicus Leaves.
AB - This study evaluates the phytochemistry, antioxidant, and antimicrobial effects
of Plectranthus amboinicus leaves extracted in different solvents. The methanol
extract contained the highest total phenolic (94.37 +/- 1.24 mg GAE/g) and
flavonoid contents (26.90 +/- 1.35 mg RE/g) and exhibited the highest DPPH
scavenging activity (90.13 +/- 3.32%) followed by the acetone extract (80.23 +/-
3.26%) at 500 MUg/mL concentration. Similarly, the highest ferric ion reduction
potential (849.63 +/- 30.95 MUM of Fe (II)/g dry weight) was exhibited by the
methanol extract followed by the acetone extract (695.92 +/- 25.44 MUM of Fe
(II)/g dry weight). The methanol extract showed greater antimicrobial activity
against all the tested pathogens (Bacillus subtilis, Methicillin-resistant
Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida
albicans). However, both hexane and acetone extracts failed to inhibit E. coli.
S. aureus and C. albicans were more susceptible to all the extracts. Further, GC
MS analysis confirmed the occurrence of a total 46 phytocompounds in different
solvent extracts. Some of the major compounds included carvacrol (37.7%),
tetracontane (16.6%), squalene (15.6%), tetrapentacontane (13.7%), and Phytol
(12.9%). In conclusion, extraction solvents influenced the recovery of
phytocompounds and the highest pharmacological activities of the methanol extract
could be correlated to the presence of additional bioactive compounds.
PMID- 28424738
TI - Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced
Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-kappaB
Pathway.
AB - Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat
inflammatory and infectious diseases including inflammatory lung diseases. The
present study was aimed at evaluating the potential therapeutic effects and
potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-)
induced acute lung injury (ALI). In this study, the mice were orally pretreated
with LFXY or dexamethasone (positive drug) before the intratracheal instillation
of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate
of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung
histopathology impairment, suppressed the excessive inflammatory responses via
decreasing the expression of proinflammatory cytokines (TNF-alpha, IL-1beta, and
IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and
repressed oxidative stress through the inhibition of MPO and MDA contents and the
upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment
with LFXY significantly prevented LPS-induced TLR4 expression and NF-kappaB (p65)
phosphorylation. Overall, the present study suggests that LFXY protected mice
from acute lung injury induced by LPS via inhibition of TLR4/NF-kappaB p65
activation and upregulation of antioxidative enzymes and it may be a potential
preventive and therapeutic agent for ALI in the clinical setting.
PMID- 28424739
TI - Rapid Screening of Potential Phosphodiesterase Inhibitors from the Roots of Ilex
pubescens Hook. et Arn. Using a Combination of Ultrafiltration and LC-MS.
AB - The cyclic nucleotide phosphodiesterase (PDE) plays an important role in
regulating the levels of second messenger molecules cAMP and cGMP. Various PDE
inhibitors have been successfully developed into drugs for targeted diseases. In
addition, PDE inhibitors can also be found in different foods and natural
medicines. In this study, ultrafiltration liquid chromatography-diode-array
detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry
(ultrafiltration LC-DAD-ESI-IT-TOF-MS) was applied to screen PDE inhibitors from
the roots of Ilex pubescens Hook. et Arn. As a result, 11 major compounds were
identified in I. pubescens roots, with nine compounds as potential PDE
inhibitors, among which five were further confirmed to be active against PDEI and
PDE5A dose-dependently in vitro, with ilexsaponin A1 and ilexsaponin B2 being the
strongest. HPLC quantification of these bioactive compounds suggested that they
are major components in the plant. The results demonstrate that ultrafiltration
LC-DAD-ESI-IT-TOF-MS is an efficient method for rapid screening of PDE inhibitors
from natural medicines.
PMID- 28424740
TI - Essential role of long non-coding RNAs in de novo chromatin modifications: the
genomic address code hypothesis.
AB - The epigenome, i.e., the whole of chromatin modifications, is transferred from
mother to daughter cells during cell differentiation. When de novo chromatin
modifications (establishment or erasure of, respectively, new or pre-existing DNA
methylations and/or histone modifications) are made in a daughter cell, however,
it has a different epigenome than its mother cell. Although de novo chromatin
modification is an important event that comprises elementary processes of cell
differentiation, its molecular mechanism remains poorly understood. We argue, in
this letter, that a key to solving this problem lies in understanding the role of
long non-coding RNAs (lncRNAs), a type of RNA that is becoming increasingly
prominent in epigenetic studies. Many studies show that lncRNAs form
ribonucleoprotein complexes in the nucleus and are involved in chromatin
modifications. However, chromatin-modifying enzymes lack the information about
genomic positions on which they act. It is known, on the other hand, that a
single-stranded RNA in general can bind to a double-stranded DNA to form a triple
helix. If each lncRNA forms a ribonucleoprotein complex with chromatin-modifying
enzymes on one hand and, at the same time, a triple helix with a genomic region
based on its specific nucleotide sequence on the other hand, it can induce de
novo chromatin modifications at specific sites. Thus, the great variety of
lncRNAs can be explained by the requirement for the diversity of "genomic address
codes" specific to their cognate genomic regions where de novo chromatin
modifications take place.
PMID- 28424742
TI - FRET from single to multiplexed signaling events.
AB - Forster resonance energy transfer (FRET) is a powerful tool for the visualization
of molecular signaling events such as protein activities and interactions in
cells. In its different implementations, FRET microscopy has been mainly used for
monitoring single events. Recently, there has been a trend of extending FRET
imaging towards the simultaneous detection of multiple events and interactions.
The concomitant increase in experimental complexity requires a deeper
understanding of the biophysical background of FRET. The presence of multiple
acceptors for one donor affects the well-known formalism for FRET between two
molecules, increasing distance sensitivity through mechanisms that have become
known as the 'antenna' and 'surplus' effect. We will discuss the nature of these
effects and present the imaging methods that have been used to unravel the
combined transfer rates in the multi-protein interactions of multiplexed FRET
experiments. Multiplexing strategies are becoming invaluable analytical tools for
the elucidation of biological complexes and for the visualization of decision
points in cellular signaling networks in physiological and pathological
conditions.
PMID- 28424741
TI - Catalytic robustness and torque generation of the F1-ATPase.
AB - The F1-ATPase is the catalytic portion of the FoF1 ATP synthase and acts as a
rotary molecular motor when it hydrolyzes ATP. Two decades have passed since the
single-molecule rotation assay of F1-ATPase was established. Although several
fundamental issues remain elusive, basic properties of F-type ATPases as motor
proteins have been well characterized, and a large part of the reaction scheme
has been revealed by the combination of extensive structural, biochemical,
biophysical, and theoretical studies. This review is intended to provide a
concise summary of the fundamental features of F1-ATPases, by use of the well
described model F1 from the thermophilic Bacillus PS3 (TF1). In the last part of
this review, we focus on the robustness of the rotary catalysis of F1-ATPase to
provide a perspective on the re-designing of novel molecular machines.
PMID- 28424743
TI - Towards Bi-Inclusive Policies: Suggestions Based on Research on Dutch Same-Sex
Attracted Young People.
AB - Dutch national LGBT policies are not bi-inclusive and this study provides
suggestions for improvement, based on empirical research. Attention for
bisexuality in policy appears simply to pay lip service and to endorse the
construction of sexual orientation as a hetero/homo binary. The outcomes of our
survey (n = 1449) and in-depth interviews (n = 38) of Dutch same-sex attracted
young people suggest that special attention for bisexual people is warranted.
Compared to exclusively same-sex attracted participants, the equally both-sex
attracted participants scored worse on openness about their sexual attraction,
visibility discomfort, perceived acceptance, and suicide attempts. Unique issues
for bisexual-identified young people were identified as follows: marginalization
of bisexuality; difficulty expressing bisexuality, particularly in relationships;
and a lack of bisexual or bi-inclusive communities. These issues were all related
to the hetero/homo binary and mononormativity. Suggested implications for more bi
inclusive policies focus on awareness of marginalization and invisibility of
bisexuality, biphobia, community and capacity building, and comprehensive
sexuality and gender education. Furthermore, rather than policies focusing on
sameness, a comprehensive diversity perspective on sexuality and gender offers
more space for bisexuality. This may be particularly relevant for young people
who are exploring their sexuality and developing a sense of their sexual self.
PMID- 28424744
TI - Oxidative Stress in Retinal Diseases.
PMID- 28417000
TI - hackseq: Catalyzing collaboration between biological and computational scientists
via hackathon.
AB - hackseq ( http://www.hackseq.com) was a genomics hackathon with the aim of
bringing together a diverse set of biological and computational scientists to
work on collaborative bioinformatics projects. In October 2016, 66 participants
from nine nations came together for three days for hackseq and collaborated on
nine projects ranging from data visualization to algorithm development. The
response from participants was overwhelmingly positive with 100% (n = 54) of
survey respondents saying they would like to participate in future hackathons. We
detail key steps for others interested in organizing a successful hackathon and
report excerpts from each project.
PMID- 28424745
TI - Distinguishing the Unique Neuropathological Profile of Blast Polytrauma.
AB - Traumatic brain injury sustained after blast exposure (blast-induced TBI) has
recently been documented as a growing issue for military personnel. Incidence of
injury to organs such as the lungs has decreased, though current epidemiology
still causes a great public health burden. In addition, unprotected civilians
sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to
moderate cases of PBLI are survivable with medical intervention, which creates a
growing population of survivors of blast-induced polytrauma (BPT) with symptoms
from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical
models simulating BPT, which is crucial to identifying unique injury mechanisms
of BPT and its management. To meet this need, our group characterized a rodent
model of BPT and compared results to a blast-induced mTBI model. Open field (OF)
performance trials were performed on rodents at 7 days after injury.
Immunohistochemistry was performed to evaluate cellular outcome at day seven
following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3
expression), and vascular damage (SMI-71) were significantly elevated in BPT
compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1alpha and
VEGF) were higher only after BPT. This study highlights the need for unique
therapeutics and prehospital management when handling BPT.
PMID- 28424747
TI - Association between Optic Nerve Head Microcirculation and Macular Ganglion Cell
Complex Thickness in Eyes with Untreated Normal Tension Glaucoma and a Hemifield
Defect.
AB - Purpose. We evaluated the association between optic nerve head (ONH)
microcirculation and macular ganglion cell complex (mGCC) thickness in patients
with untreated normal tension glaucoma (NTG) and a hemifield defect. Methods. The
medical records of 47 patients with untreated NTG were retrospectively reviewed.
Laser speckle flowgraphy was used to obtain mean blur rate (MBR), a relative
measure of blood flow. Average total deviation (TD), mGCC, and the
circumpapillary retinal nerve fiber layer (cpRNFL) thickness were also analyzed.
Results. All parameters corresponding to the defective hemifield were
significantly lower than those corresponding to the normal hemifield. In the
defective hemifield, MBR was correlated with TD, mGCC, and cpRNFL thickness. In
the normal hemifield, MBR was only correlated with mGCC thickness, and multiple
regression analysis showed that mGCC thickness was a significant contributing
factor of the MBR. Conclusion. MBR was well correlated with mGCC thickness in
eyes with untreated NTG and a hemifield defect. In the normal hemifield, mGCC
thickness was a contributing factor of the MBR indicating that ONH circulatory
dysfunction may be associated with retinal structural changes in the early stages
of glaucoma. A reduction in ONH microcirculation may be an early indicator of the
presence and progression of glaucoma.
PMID- 28424748
TI - Immigrant Arrival and Tuberculosis among Large Immigrant- and Refugee-Receiving
Countries, 2005-2009.
AB - Objective. Tuberculosis control in foreign-born populations is a major public
health concern for Australia, Canada, New Zealand, United Kingdom, and the United
States, large immigrant- and refugee-receiving countries that comprise the
Immigration and Refugee Health Working Group (IRHWG). Identifying and comparing
immigration and distribution of foreign-born tuberculosis cases are important for
developing targeted and collaborative interventions. Methods. Data stratified by
year and country of birth from 2005 to 2009 were received from these five
countries. Immigration totals, tuberculosis case totals, and multidrug-resistant
tuberculosis (MDR TB) case totals from source countries were analyzed and
compared to reveal similarities and differences for each member of the group.
Results. Between 2005 and 2009, there were a combined 31,785,002 arrivals, 77,905
tuberculosis cases, and 888 MDR TB cases notified at the federal level in the
IRHWG countries. India, China, Vietnam, and the Philippines accounted for 41.4%
of the total foreign-born tuberculosis cases and 42.7% of the foreign-born MDR
tuberculosis cases to IRHWG. Interpretation. Collaborative efforts across a small
number of countries have the potential to yield sizeable gains in tuberculosis
control for these large immigrant- and refugee-receiving countries.
PMID- 28424749
TI - Development of Asymmetric Facial Depigmentation in a Patient Treated with
Dasatinib with New-Onset Hypovitaminosis D: Case Report and Review of the
Literature.
AB - Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat
imatinib-resistant chronic myelogenous leukemia (CML), as well as other
Philadelphia chromosome-positive lymphoproliferative disorders. While the most
commonly reported cutaneous side effects with this therapy include a morbilliform
eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have
also been observed, albeit much more rarely. We present the case of a 72-year-old
South Asian male with CML who presented with new-onset hypopigmentation of his
face and scalp three years after a dose increase of dasatinib therapy, in the
setting of newly discovered borderline hypovitaminosis D. Dasatinib and the other
TKIs are believed to induce dyschromias via modulation of the c-kit receptor and
its associated signaling pathway, which is involved in melanocyte survival,
proliferation, and migration.
PMID- 28424750
TI - Celiac Disease Presenting with Immune Thrombocytopenic Purpura.
AB - Celiac disease (CD) is an immunological disorder. Clinical manifestations occur
as a result of intestinal mucosa damage and malabsorption. CD is also associated
with extraintestinal manifestations and autoimmune disorders. The coexistence of
CD and autoimmune diseases has been described before. In this article, a patient
with CD presenting with thrombocytopenia is discussed.
PMID- 28424751
TI - Levodopa Responsive Parkinsonism in Patients with Hemochromatosis: Case
Presentation and Literature Review.
AB - Hemochromatosis is an autosomal recessive disorder which leads to abnormal iron
deposition in the parenchyma of multiple organs causing tissue damage.
Accumulation of iron in the brain has been postulated to be associated with
several neurodegenerative diseases including Parkinson's disease. The excess iron
promotes Parkin and alpha-synuclein aggregation in the neurons. Excess iron has
also been noted in substantia nigra on MRI especially using susceptibility
weighted imaging in patients with Parkinson's disease. We present a case of a
young male with alleles for both C282Y and H63D who presented with signs of
Parkinsonism and demonstrated significant improvement with levodopa treatment.
PMID- 28424752
TI - Cocaine-Like Discriminative Stimulus Effects of Mephedrone and Naphyrone in Mice.
AB - BACKGROUND: In recent years, commercial bath salts products containing synthetic
cathinone analogues have emerged as illicit drugs of abuse. These cathinones are
structurally similar to the psychostimulants 3,4-methylenedioxymethamphetamine
(MDMA) and methamphetamine (METH), and produce their effects via interactions
with monoamine transporters, where smaller compounds (e.g., mephedrone) are
amphetamine-like monoamine releasers, while the structurally larger compounds
(e.g., naphyrone) are cocaine-like monoamine reuptake inhibitors. Individual
cathinones also differ from one another with respect to selectivity among the
three monoamine transporters. STATEMENT OF PURPOSE OF STUDY: This study was
designed to assess the cocaine-like interoceptive effects of synthetic cathinone
analogues functioning as passive monoamine reuptake inhibitors (naphyrone) or as
releasers (mephedrone) in mice in order to compare effectiveness (degree of
substitution) and potency with positive control psychostimulants cocaine, METH,
and MDMA. PROCEDURES: In the present study, mice were trained to discriminate 10
mg/kg cocaine from saline, and substitutions with METH, MDMA, mephedrone,
naphyrone, and morphine were performed. MAIN FINDINGS: Mice reliably
discriminated the cocaine training dose from saline, and METH, MDMA, mephedrone,
and naphyrone all elicited full cocaine-like responding, while morphine did not.
Potency differences were observed such that METH was most potent, while
mephedrone, cocaine, MDMA, and naphyrone exhibited roughly equivalent potency.
PRINCIPAL CONCLUSIONS: These data confirm that interaction with DAT is an
important component of cocaine-like discriminative stimulus effects, and suggest
that synthetic cathinones likely elicit psychostimulant-like abuse-related
effects.
PMID- 28424753
TI - Image-Guided High Intensity Focused Ultrasound System for Large Animal Nerve
Ablation Studies.
AB - High intensity focused ultrasound (HIFU) is a form of thermal ablation technique,
which can treat a variety of medical afflictions. One promising therapeutic use
is the permanent destruction of nerves non-invasively in patients with severe
spasticity or certain types of pain (e.g., phantom limb pain). To this end, HIFU
requires ultrasound guidance, which allows the non-invasive, target-specific
deposition of thermal energy to the targeted nerve, thereby blocking axonal
conduction. In this paper, a composite system comprising both ultrasound-imaging
and HIFU therapy was developed and used to induce localized non-invasive nerve
blockage in an in vivo large animal study. Five pigs were used with the femoral
nerve as the target. Calibrated needle thermocouples inserted at the target site
were employed to monitor the target tissue temperature. The degree of nerve
blockage was assessed by measuring compound action potential (CAP) signal with a
clinical nerve electrophysiology system before and after HIFU exposures. An
average CAP signal amplitude reduction of 49% of baseline with a standard
deviation of 9% was observed after 20-30 min post exposure. These results
demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a
potential non-invasive nerve ablation method.
PMID- 28424754
TI - Considerations of temperature in the context of the persistence classification in
the EU.
AB - Simulation degradation studies for industrial chemicals, biocidal products and
plant protection products are required in the EU to estimate half-lives in soil,
water and sediment for the comparison to persistence criteria for hazard (P/vP)
assessment, and for use in exposure assessments. There is a discrepancy between
European regulatory approaches regarding the temperature at which degradation
half-lives should be (1) measured in simulation degradation testing of
environmental compartments, and (2) compared to the P/vP criteria. In this paper,
an opinion is provided on the options for the experimental temperature and
extrapolation to other conditions. A review of the historical development of
persistence criteria did not give conclusive evidence of the temperature at which
the half-lives that underpin the P-criteria were measured, but room temperature
is likely. Half-lives measured at 20 degrees C are in line with the intentions
of some international agreements, but in the EU there is a continued political
debate regarding the relevant temperature for comparison with persistence
criteria. Measuring degradation at 20 degrees C has the advantage that
metabolites/transformation products can be identified with greater accuracy, and
that kinetic fits to determine half-lives for parent compounds and metabolites
carry less uncertainty. Extrapolation of half-lives to lower temperatures is
possible for assessing environmental exposure, but the uncertainty of the
persistence classification is smaller when measured half-lives are used for
direct comparison with P/vP criteria, without extrapolation. Model simulations
demonstrate the pattern of concentrations that can be expected for realistic
worst case climate scenarios in the EU based on the half-life of 120 days in soil
at 20 degrees C and of 40 days in water at 20 degrees C, and their temporal and
spatial variability.
PMID- 28424755
TI - Rapid, low cost prototyping of transdermal devices for personal healthcare
monitoring.
AB - The next generation of devices for personal healthcare monitoring will comprise
molecular sensors to monitor analytes of interest in the skin compartment.
Transdermal devices based on microneedles offer an excellent opportunity to
explore the dynamics of molecular markers in the interstitial fluid, however good
acceptability of these next generation devices will require several technical
problems associated with current commercially available wearable sensors to be
overcome. These particularly include reliability, comfort and cost. An essential
pre-requisite for transdermal molecular sensing devices is that they can be
fabricated using scalable technologies which are cost effective. We present here
a minimally invasive microneedle array as a continuous monitoring platform
technology. Method for scalable fabrication of these structures is presented. The
microneedle arrays were characterised mechanically and were shown to penetrate
human skin under moderate thumb pressure. They were then functionalised and
evaluated as glucose, lactate and theophylline biosensors. The results suggest
that this technology can be employed in the measurement of metabolites,
therapeutic drugs and biomarkers and could have an important role to play in the
management of chronic diseases.
PMID- 28424756
TI - Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.
AB - Retroviral vector gene therapy is a promising approach to treating HIV-1.
However, integrated vectors are mutagens with the potential to dysregulate nearby
genes and cause severe adverse side effects. Leukemia has already been a
documented severe adverse event in gene therapy clinical trials for the treatment
of primary immunodeficiencies. These side effects will need to be reduced or
avoided if retroviral vectors are to be used clinically for HIV-1 treatment. The
addition of chromatin insulators to retroviral vectors is a potential strategy
for reducing adverse side effects. Insulators have already been effectively used
in retroviral vectors to reduce genotoxicity in pre-clinical studies. Here, we
will review how insulators function, genotoxicity in gene therapy clinical
trials, the design of insulated retroviral vectors, promising results from
insulated retroviral vector studies, and considerations for the development of
insulated retroviral treatment vectors for HIV-1 gene therapy.
PMID- 28424757
TI - The Emerging Role of Targeted Therapy and Immunotherapy in the Management of
Brain Metastases in Non-Small Cell Lung Cancer.
AB - Lung cancer is the worldwide leading cause of cancer-related mortality in men and
second leading in women. Brain metastases (BM) account for 10% of non-small cell
lung cancer (NSCLC) patients at initial presentation, with another 25-40%
developing BM during the course of their disease. In the last decade, the field
of precision oncology has led to the discovery of a multitude of heterogenous
molecular abnormalities within NSCLC as well as the development of tyrosine
kinase inhibitors that target them. In this review, the focus will be on targeted
therapy and immunotherapy that show efficacy in BM rather than conventional
treatment for multiple BM (such as surgical resection, WBRT, or stereotactic
radiosurgery).
PMID- 28424758
TI - Redox-Related Epigenetic Mechanisms in Glioblastoma: Nuclear Factor (Erythroid
Derived 2)-Like 2, Cobalamin, and Dopamine Receptor Subtype 4.
AB - Glioblastoma is an exceptionally difficult cancer to treat. Cancer is universally
marked by epigenetic changes, which play key roles in sustaining a malignant
phenotype, in addition to disease progression and patient survival. Studies have
shown strong links between the cellular redox state and epigenetics. Nuclear
factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription
factor that upregulates endogenous antioxidant production, and is aberrantly
expressed in many cancers, including glioblastoma. Methylation of DNA and
histones provides a mode of epigenetic regulation, and cobalamin-dependent
reactions link the redox state to methylation. Antagonists of dopamine receptor
subtype 4 (D4 receptor) were recently shown to restrict glioblastoma stem cell
growth by downregulating trophic signaling, resulting in inhibition of functional
autophagy. In addition to stimulating glioblastoma stem cell growth, D4 receptors
have the unique ability to catalyze cobalamin-dependent phospholipid methylation.
Therefore, D4 receptors represent an important node in a molecular reflex pathway
involving Nrf2 and cobalamin, operating in conjunction with redox status and
methyl group donor availability. In this article, we describe the redox-related
effects of Nrf2, cobalamin metabolism, and the D4 receptor on the regulation of
the epigenetic state in glioblastoma.
PMID- 28424759
TI - Antiangiogenesis for Advanced Non-Small-Cell Lung Cancer in the Era of
Immunotherapy and Personalized Medicine.
AB - Over the past decade, patients with advanced non-small-cell lung cancer (NSCLC)
have witnessed substantial advances in regards to therapeutic alternatives. Among
newly developed agents, angiogenesis inhibitors were extensively tested in
different settings and have produced some favorable outcomes despite several
shortcomings. Bevacizumab is the most examined agent in this context and has
demonstrated significant survival benefits when combined with standard
chemotherapy in eligible patients. Preliminary results on the addition of
bevacizumab to erlotinib in patients with EGFR-mutated NSCLC seem promising.
Other antiangiogenic agents were also tested, but ramucirumab and nintedanib are
the only agents with a positive impact on survival. More recently, immune
checkpoint inhibitors (ICIs) have had considerable success due to their prolonged
durations of response, yet response rates are still deemed suboptimal, and
various combination therapies are being tested in an effort to improve efficacy.
Preclinical evidence suggests an immunosuppressive effect of pro-angiogenic
factors, which sets up a plausible rationale for combining ICIs and
antiangiogenic agents. Herein, we review the landmark data supporting the success
of angiogenesis inhibitors, and we discuss the potential for combination with
immunotherapy and targeted agents.
PMID- 28424760
TI - Insights into Local Tumor Microenvironment Immune Factors Associated with
Regression of Cutaneous Melanoma Metastases by Mycobacterium bovis Bacille
Calmette-Guerin.
AB - Mycobacterium bovis bacille Calmette-Guerin (BCG) is listed as an intralesional
(IL) therapeutic option for inoperable stage III in-transit melanoma in the
National Comprehensive Cancer Network Guidelines. Although the mechanism is
unknown, others have reported up to 50% regression of injected lesions, and 17%
regression of uninjected lesions in immunocompetent patients after direct
injection of BCG into metastatic melanoma lesions in the skin. BCG and other
mycobacteria express ligands capable of stimulating the gamma9delta2 T cells.
Therefore, we hypothesized that gamma9delta2 T cells play a role in promoting BCG
mediated antitumor immunity in patients treated with IL-BCG for in-transit
cutaneous melanoma metastases. Indeed, we found gamma9delta2 T cell infiltration
in melanoma skin lesions during the course of IL-BCG treatment. Gene expression
analysis revealed that BCG injection elicits the expression of a vast array of
chemokines in tumor lesions, including strong expression of CXCL9, 10, and 11, a
set of chemokines that attract T cells expressing the CXCR3 chemokine receptor.
In corroboration with our hypothesis, approximately 85% of gammadelta T cells
express high levels of CXCR3 on their surface. Importantly, the injected tumor
lesions also express genes whose protein products are the antigenic ligands for
gammadelta T cells (BTN3A1 and MICB), and the cytokines that are the typical
products of activated gammadelta T cells. Interestingly, we also found that
gammadelta T cells infiltrate the regressed lesions that did not receive BCG
injections. Our study suggests that gamma9delta2 T cells may contribute to
melanoma regression induced by IL-BCG treatment.
PMID- 28424761
TI - Sequencing of blaIMP-Carrying IncN2 Plasmids, and Comparative Genomics of IncN2
Plasmids Harboring Class 1 Integrons.
AB - This work presents the complete nucleotide sequences of p0801-IMP from Klebsiella
pneumoniae, p7121-IMP from K. oxytoca, and p17285-IMP from Citrobacter freundii,
which are recovered from three different cases of nosocomial infection. These
three plasmids represent the first fully sequenced blaIMP-carrying IncN2
plasmids. Further comparative genomics analysis of all the five integron-carrying
IncN2 plasmids p0801-IMP, p7121-IMP, p17285-IMP, pJIE137, and p34983-59.134kb
indicates that they possess conserved IncN2 backbones with limited genetic
variations with respect to gene content and organization. Four class 1 integrons
(blaIMP-1-carrying In1223 in p0801-IMP/p7121-IMP, blaIMP-8-carrying In655 in
p17285-IMP, In27 in pJIE137, and In1130 in p34983-59.134kb), two insertion
sequence-based transposition units (ISEcp1-orfRA1-14 in p17285-IMP, and ISEcp1
blaCTX-M-62-Deltaorf477-orfRA1-14 in pJIE137), and a novel Tn1696-related
transposon Tn6325 carrying In1130 in p34983-59.134kb are indentified in the
plasmid accessory regions. In1223 and In655 represent ancestral Tn402-associated
integrons, while In27 and In1130 belong to complex class 1 integrons. The
relatively small IncN2 backbones are able to integrate different mobile elements
which carry various resistance markers, promoting the accumulation and spread of
antimicrobial resistance genes among enterobacterial species.
PMID- 28424762
TI - Assessment of Sensory Processing Characteristics in Children between 3 and 11
Years Old: A Systematic Review.
AB - The assessment of sensory perception, discrimination, integration, modulation,
praxis, and other motor skills, such as posture, balance, and bilateral motor
coordination, is necessary to identify the sensory and motor factors influencing
the development of personal autonomy. The aim of this work is to study the
assessment tools currently available for identifying different patterns of
sensory processing. There are 15 tests available that have psychometric
properties, primarily for the US population. Nine of them apply to children in
preschool and up to grade 12. The assessment of sensory processing is a process
that includes the use of standardized tests, administration of caregiver
questionnaires, and clinical observations. The review of different studies using
PRISMA criteria or Osteba Critical Appraisal Cards reveals that the most commonly
used tools are the Sensory Integration and Praxis Test, the Sensory Processing
Measure, and the Sensory Profile.
PMID- 28424763
TI - Airway Problems in Neonates-A Review of the Current Investigation and Management
Strategies.
AB - Airway problems in the neonatal population are often life threatening and raise
challenging issues in diagnosis and management. The airway problems can result
from congenital or acquired lesions and can be broadly classified into those
causing obstruction or those due to an abnormal "communication" in the airway.
Many different investigations are now available to identify the diagnosis and
quantify the severity of the problem, and these tests can be simple or invasive.
Bronchography and bronchoscopy are essential to determine the extent and severity
of the airway problem and to plan treatment strategy. Further imaging techniques
help to delineate other commonly associated abnormalities. Echocardiography is
also important to confirm any associated cardiac abnormality. In this review, the
merits and disadvantages of the various investigations now available to the
clinician will be discussed. The current therapeutic strategies are discussed,
and the review will focus on the most challenging conditions that cause the
biggest management conundrums, specifically laryngotracheal cleft, congenital
tracheal stenosis, and tracheobronchomalacia. Management of acquired stenosis
secondary to airway injury from endotracheal intubation will also be discussed as
this is a common problem. Slide tracheoplasty is the preferred surgical option
for long-segment tracheal stenosis, and results have improved significantly.
Stents are occasionally required for residual or recurrent stenosis following
surgical repair. There is sufficient evidence that a multidisciplinary team
approach for managing complex airway issues provides the best results for the
patient. There is ongoing progress in the field with newer diagnostic tools as
well as development of innovative management techniques, such as biodegradable
stents and stem cell-based tracheal transplants, leading to a much better
prognosis for these children in the future.
PMID- 28424766
TI - The Need for Hematology Nurse Education in Low- and Middle-Income Countries: A
Community Case Study in Tanzania.
AB - Hematology-related diseases, such as anemia, malaria, sickle cell disease (SCD),
and blood cancers, have differing rates of survival between high-income and low-
and middle-income countries (LMICs). Nurses in LMICs have an unmet need for
specialty training and education to address hematology and hemato-oncology
disorders. A gap in the literature exists about hematology nurse education and
clinical service demands in LMICs. This community case study documents a
collaborative hematology and basic hemato-oncology education program to
sustainably strengthen nurse capacity at a national referral hospital and
university in Tanzania. The goal of the intervention was to provide culturally
competent nurse training in pediatric and adult hematology. A certified pediatric
nurse practitioner with hematology and oncology experience provided culturally
competent training and staff development to nurses over two weeks to meet this
goal. Prior to development of a training schedule, nurses confidentially
identified five of their top learning needs. Main hematology and basic oncology
educational needs identified by nurses were the management of anemia, safe
handling of cytotoxic agents, and treatment of SCD. The format of the education
varied from bedside teaching to formal presentations to one-on-one individual
discussions. Overall, nurses expressed satisfaction with the education and
verbalized appreciation for teaching and training activities tailored to meet
their needs. Specialized training in hematology and hemato-oncology has the
potential to increase nurses' confidence, respect, and participation in
interprofessional team decision-making. Lessons learned from the impact of
collaborative nurse education and partnership in Tanzania can be generalized to
other LMICs. This community case study highlights the importance of specialty
nurse education, interprofessional development, and global partnerships needed to
improve patient outcomes.
PMID- 28424765
TI - Community Health Volunteers in Primary Healthcare in Rural Uganda: Factors
Influencing Performance.
AB - INTRODUCTION: Community health volunteers (CHVs) play an integral role in primary
healthcare. Several countries rely on CHV programs as a major element in
improving access to care and attaining universal health coverage. However, their
performance has been heterogeneous and at times context-specific, and influenced
by multiple factors. We describe the socio-demographic and workplace
characteristics affecting CHVs' performance in a public health program in rural
western Uganda. METHODS: This was a cross-sectional study based on routine
program data of CHVs serving the catchment of Bwindi Community Hospital, Kanungu
District, South Western Uganda, in 2014 and 2015. Information was collected on
individual socio-demographic and workplace characteristics of the CHVs. To assess
their work output, we defined study-specific targets in terms of attendance at
monthly CHVs' meetings with community health nurses, households followed-up and
reported, children screened for malnutrition, immunization coverage, and health
facility deliveries. Frequencies and proportions are reported for characteristics
and outputs and odds ratios for study-specific factors associated with overall
performance. RESULTS: Of the 508 CHVs, 65% were women, 48% were aged 35 years and
below, and 37% took care of more than the recommended 20-30 households. Seventy
eight percent of the CHVs had >=80% of pregnant women under their care delivering
in health units, 71% had >=95% of the children on schedule for routine
immunization, while 27% screened >=75% of the children under 5 years for
malnutrition. More refresher trainings was associated with better overall
performance [adjusted odds ratio (aOR): 12.2, 95% confidence interval (CI): 1.6
93.6, P = 0.02] while overseeing more than the recommended 20-30 households
reduced overall performance (aOR: 0.6, 95% CI: 0.4-0.9, P = 0.02). CONCLUSION:
Being in-charge of more than the recommended households was associated with
reduced performance of CHVs, while more refresher trainings were associated with
improved performance. If the CHVs are to remain a strategic pillar in universal
health coverage, it is imperative to address those factors known to impact on
their performance.
PMID- 28424764
TI - Diffusion Tensor Imaging Colour Mapping Threshold for Identification of
Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm
Lambs.
AB - PURPOSE: The aim of this study is to examine whether advanced magnetic resonance
imaging (MRI) techniques can detect early brain injury caused by intrauterine
inflammation and inappropriate initial respiratory support in preterm lambs.
HYPOTHESIS: Neuropathology caused by intrauterine inflammation is exacerbated by
mechanical ventilation at birth and is detectable with advanced MRI techniques.
METHODS: Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) 7 days
prior to delivery at ~125 days of gestation (85% of gestation), whereupon lambs
were delivered and randomised to receive an injurious (LPS + INJ, n = 6) or
protective (LPS + PROT, n = 6) ventilation strategy. MRI of the brain was
conducted 90 min after preterm delivery, using structural, diffusion tensor
imaging (DTI), and magnetic resonance spectroscopy (MRS) techniques. A colour map
threshold technique was utilised to compare distributions of low diffusivity
voxels in the brains of LPS-exposed lambs with those not exposed to LPS (PROT, n
= 7 PROT and INJ, n = 10). RESULTS: No overt cerebral injury was identified on
structural MRI images of any lamb. However, on DTI, axial diffusivity, radial
diffusivity, and mean diffusivity values were lower and significantly more
heterogeneous in specific brain regions of lambs in the LPS + INJ group compared
to the LPS + PROT group. Colour mapping revealed lower diffusivity in the
thalamus, periventricular white matter, internal capsule, and frontal white
matter in the LPS + INJ group compared to LPS + PROT group. The MRS peak area
ratios of lactate, relative to those for the metabolites creatine, choline, and N
acetylaspartate, were not different between LPS-exposed groups. Lambs exposed to
LPS had lower diffusivity within the white matter regions assessed than non-LPS
treated control lambs. CONCLUSION: DTI colour map threshold techniques detected
early brain injury in preterm lambs exposed to intrauterine inflammation and
detected differences between injurious and protective ventilation strategies. DTI
mapping approaches are potentially useful for early detection of subtle brain
injury in premature infants.
PMID- 28424767
TI - Direct and Indirect Costs of Asthma Management in Greece: An Expert Panel
Approach.
AB - OBJECTIVE: Asthma is a major cause of morbidity and mortality and is associated
with significant economic burden worldwide. The objectives of this study were to
map current resource use associated with the disease management and to estimate
the annual direct and indirect costs per adult patient with asthma. METHODS: A
Delphi panel with seven leading pulmonologists was conducted. A semistructured
questionnaire was developed to elicit data on resource use and treatment
patterns. Unit costs from official, published sources were subsequently assigned
to resource use to estimate direct medical costs. Indirect costs were estimated
as number of work loss days. Cost base year was 2015, and the perspective adopted
was that of the National Organization of Health Care Services Provision, as well
as the societal. RESULTS: Patients with asthma are mainly managed by
pulmonologists (71.4%) and secondarily by general practitioners and internists
(28.6%). The annual cost of managing exacerbations was estimated at ?273.1, while
maintenance costs were estimated at ?1,100.2 per year. Total costs of managing
asthma per patient per year were estimated at ?2,281.8, 64.4% of which
represented direct medical costs. Of the direct costs, pharmaceutical treatment
was the key driver, accounting for 63.9 and 41.2% of direct and total costs,
respectively. Direct non-medical costs (patient travel and waiting time) were
estimated at ?152.3. Indirect costs accounted for 28.9% of total costs.
CONCLUSION: Asthma is a chronic condition, the management of which constrains the
already limited Greek health care resources. The increasing prevalence of the
disease raises concerns as it could translate per patient costs into a
significant burden for the Greek health care system. Thus, the prevention, self
management, and improved quality of care for asthma should find a place in the
health policy agenda in Greece.
PMID- 28424768
TI - Model-Based Policymaking: A Framework to Promote Ethical "Good Practice" in
Mathematical Modeling for Public Health Policymaking.
AB - Mathematical models are increasingly relied upon as decision support tools, which
estimate risks and generate recommendations to underpin public health policies.
However, there are no formal agreements about what constitutes professional
competencies or duties in mathematical modeling for public health. In this
article, we propose a framework to evaluate whether mathematical models that
assess human and animal disease risks and control strategies meet standards
consistent with ethical "good practice" and are thus "fit for purpose" as
evidence in support of policy. This framework is derived from principles of
biomedical ethics: independence, transparency (autonomy), beneficence/non
maleficence, and justice. We identify ethical risks associated with model
development and implementation and consider the extent to which scientists are
accountable for the translation and communication of model results to
policymakers so that the strengths and weaknesses of the scientific evidence base
and any socioeconomic and ethical impacts of biased or uncertain predictions are
clearly understood. We propose principles to operationalize a framework for
ethically sound model development and risk communication between scientists and
policymakers. These include the creation of science-policy partnerships to
mutually define policy questions and communicate results; development of
harmonized international standards for model development; and data stewardship
and improvement of the traceability and transparency of models via a searchable
archive of policy-relevant models. Finally, we suggest that bespoke ethical
advisory groups, with relevant expertise and access to these resources, would be
beneficial as a bridge between science and policy, advising modelers of potential
ethical risks and providing overview of the translation of modeling advice into
policy.
PMID- 28424770
TI - Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs.
AB - There is a growing demand for alternative fabrication approaches to develop
tissues and organs as conventional techniques are not capable of fabricating
constructs with required structural, mechanical, and biological complexity. 3D
bioprinting offers great potential to fabricate highly complex constructs with
precise control of structure, mechanics, and biological matter [i.e., cells and
extracellular matrix (ECM) components]. 3D bioprinting is an additive
manufacturing approach that utilizes a "bioink" to fabricate devices and
scaffolds in a layer-by-layer manner. 3D bioprinting allows printing of a cell
suspension into a tissue construct with or without a scaffold support. The most
common bioinks are cell-laden hydrogels, decellulerized ECM-based solutions, and
cell suspensions. In this mini review, a brief description and comparison of the
bioprinting methods, including extrusion-based, droplet-based, and laser-based
bioprinting, with particular focus on bioink design requirements are presented.
We also present the current state of the art in bioink design including the
challenges and future directions.
PMID- 28424769
TI - Folates in Plants: Research Advances and Progress in Crop Biofortification.
AB - Folates, also known as B9 vitamins, serve as donors and acceptors in one-carbon
(C1) transfer reactions. The latter are involved in synthesis of many important
biomolecules, such as amino acids, nucleic acids and vitamin B5. Folates also
play a central role in the methyl cycle that provides one-carbon groups for
methylation reactions. The important functions fulfilled by folates make them
essential in all living organisms. Plants, being able to synthesize folates de
novo, serve as an excellent dietary source of folates for animals that lack the
respective biosynthetic pathway. Unfortunately, the most important staple crops
such as rice, potato and maize are rather poor sources of folates. Insufficient
folate consumption is known to cause severe developmental disorders in humans.
Two approaches are employed to fight folate deficiency: pharmacological
supplementation in the form of folate pills and biofortification of staple crops.
As the former approach is considered rather costly for the major part of the
world population, biofortification of staple crops is viewed as a decent
alternative in the struggle against folate deficiency. Therefore, strategies,
challenges and recent progress of folate enhancement in plants will be addressed
in this review. Apart from the ever-growing need for the enhancement of
nutritional quality of crops, the world population faces climate change
catastrophes or environmental stresses, such as elevated temperatures, drought,
salinity that severely affect growth and productivity of crops. Due to immense
diversity of their biochemical functions, folates take part in virtually every
aspect of plant physiology. Any disturbance to the plant folate metabolism leads
to severe growth inhibition and, as a consequence, to a lower productivity.
Whereas today's knowledge of folate biochemistry can be considered very profound,
evidence on the physiological roles of folates in plants only starts to emerge.
In the current review we will discuss the implication of folates in various
aspects of plant physiology and development.
PMID- 28424772
TI - Putting Cells into Context.
PMID- 28424771
TI - PTK7 Faces the Wnt in Development and Disease.
AB - PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane
receptor regulating various processes in embryonic development and tissue
homeostasis. On a cellular level PTK7 affects the establishment of cell polarity,
the regulation of cell movement and migration as well as cell invasion. The PTK7
receptor has been shown to interact with ligands, co-receptors, and intracellular
transducers of Wnt signaling pathways, pointing to a function in the fine-tuning
of the Wnt signaling network. Here we will review recent findings implicating
PTK7 at the crossroads of Wnt signaling pathways in development and disease.
PMID- 28424773
TI - Septins Focus Cellular Growth for Host Infection by Pathogenic Fungi.
AB - One of the key challenges faced by microbial pathogens is invasion of host
tissue. Fungal pathogens adopt a number of distinct strategies to overcome host
cell defenses, including the development of specialized infection structures, the
secretion of proteins that manipulate host responses or cellular organization,
and the ability to facilitate their own uptake by phagocytic mechanisms. Key to
many of these adaptations is the considerable morphogenetic plasticity displayed
by pathogenic species. Fungal pathogens can, for example, shift their growth
habit between non-polarized spores, or yeast-like cells, and highly polarized
hyphal filaments. These polarized filaments can then elaborate differentiated
cells, specialized to breach host barriers. Septins play fundamental roles in the
ability of diverse fungi to undergo shape changes and organize the F-actin
cytoskeleton to facilitate invasive growth. As a consequence, septins are
increasingly implicated in fungal pathogenesis, with many septin mutants
displaying impairment in their ability to cause diseases of both plants and
animals. In this mini-review, we show that a common feature of septin mutants is
the emergence of extra polar outgrowths during morphological transitions, such as
emergence of germ tubes from conidia or branches from hyphae. We propose that
because septins detect and stabilize membrane curvature, they prevent extra polar
outgrowths and thereby focus fungal invasive force, allowing substrate invasion.
PMID- 28424774
TI - Cardiac Radionuclide Imaging in Rodents: A Review of Methods, Results, and
Factors at Play.
AB - The interest around small-animal cardiac radionuclide imaging is growing as
rodent models can be manipulated to allow the simulation of human diseases. In
addition to new radiopharmaceuticals testing, often researchers apply well
established probes to animal models, to follow the evolution of the target
disease. This reverse translation of standard radiopharmaceuticals to rodent
models is complicated by technical shortcomings and by obvious differences
between human and rodent cardiac physiology. In addition, radionuclide studies
involving small animals are affected by several extrinsic variables, such as the
choice of anesthetic. In this paper, we review the major cardiac features that
can be studied with classical single-photon and positron-emitting
radiopharmaceuticals, namely, cardiac function, perfusion and metabolism, as well
as the results and pitfalls of small-animal radionuclide imaging techniques. In
addition, we provide a concise guide to the understanding of the most frequently
used anesthetics such as ketamine/xylazine, isoflurane, and pentobarbital. We
address in particular their mechanisms of action and the potential effects on
radionuclide imaging. Indeed, cardiac function, perfusion, and metabolism can all
be significantly affected by varying anesthetics and animal handling conditions.
PMID- 28424775
TI - Second-line Treatment of Non-Small Cell Lung Cancer: Focus on the Clinical
Development of Dacomitinib.
AB - Dacomitinib is a second-generation, irreversible, covalent pan-HER tyrosine
kinase inhibitor (TKI). It showed potent EGFR signaling inhibition in
experimental models, including first-generation TKI-resistant non-small cell lung
cancer (NSCLC) cell lines. This preclinical efficacy did not translate into
clinically meaningful treatment benefits for advanced, pretreated, molecularly
unselected NSCLC patients enrolled in two parallel phase III trials. Dacomitinib
and erlotinib showed overlapping efficacy data in chemotherapy-pretreated EGFR
wild-type (WT) patients in the ARCHER 1009 trial. Similarly, it failed to
demonstrate any survival benefits as compared to placebo in EGFR WT subsets
progressing on chemotherapy and at least one previous first-generation TKI
(erlotinib or gefitinib) in the BR.26 trial. In the case of EGFR-mutant NSCLCs, a
pooled analysis of the ARCHER 1009 and ARCHER 1028 trials comparing the efficacy
of dacomitinib vs. erlotinib in chemotherapy-pretreated, EGFR TKI-naive patients
showed a trend to a longer progression-free survival (PFS) and overall survival
in favor of dacomitinib that did not reach statistical significance, with a
higher rate of treatment related adverse events (mainly skin rash, paronychia,
and gastrointestinal toxicities). On the other hand, the clinical activity in
patients with EGFR-mutant NSCLCs with acquired TKI resistance that were included
in phase II/III trials was equally poor (response rate <10%; PFS 3-4 months).
Therefore, with the results of the ARCHER 1050 trial (NCT01774721) still pending,
the current clinical development of dacomitinib is largely focused on EGFR
mutant, TKI-naive patients. Here, we review the most relevant clinical data of
dacomitinib in advanced NSCLC. We discuss the potential role of dacomitinib in
pretreated EGFR WT and EGFR-mutant (TKI-naive and TKI-resistant) patients.
Finally, we briefly comment the available clinical data of dacomitinib in HER2
mutant NSCLC patients.
PMID- 28424776
TI - Socially Responsible Surgery: Building Recognition and Coalition.
AB - IMPORTANCE: Socially responsible surgery (SRS) integrates surgery and public
health, providing a framework for research, advocacy, education, and clinical
practice to address the social barriers of health that decrease surgical access
and worsen surgical outcomes in underserved patient populations. These patients
face disparities in both health and in health care, which can be effectively
addressed by surgeons in collaboration with allied health professionals.
OBJECTIVE: We reviewed the current state of surgical access and outcomes of
underserved populations in American rural communities, American urban
communities, and in low- and middle-income countries. EVIDENCE REVIEW: We
searched PubMed using standardized search terms and reviewed the reference lists
of highly relevant articles. We reviewed the reports of two recent global surgery
commissions. CONCLUSION: There is an opportunity for scholarship in rural
surgery, urban surgery, and global surgery to be unified under the concept of
SRS. The burden of surgical disease and the challenges to management demonstrate
that achieving optimal health outcomes requires more than excellent perioperative
care. Surgeons can and should regularly address the social determinants of health
experienced by their patients. Formalized research and training opportunities are
needed to meet the growing enthusiasm among surgeons and trainees to develop
their practice as socially responsible surgeons.
PMID- 28424777
TI - Influence of Cellular Composition and Exogenous Activation on Growth Factor and
Cytokine Concentrations in Canine Platelet-Rich Plasmas.
AB - OBJECTIVE: The purposes of this study were to (1) evaluate correlations among
platelet, leukocyte, growth factor, and cytokine concentrations in canine
platelet-rich plasmas (PRPs) produced from five different canine PRP
concentrating systems and (2) compare the effects of different activation
protocols on platelet activation and growth factor release from one of these
PRPs. METHODS: PRP was made using blood from 15 dogs and each of 5 different PRP
systems in a cross-over design. Complete blood counts were performed to quantify
platelet and leukocyte concentrations. PRPs were activated, or not, according to
manufacturer instructions, and transforming growth factor-beta1 (TGF-beta1),
platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor,
and tumor necrosis factor-alpha (TNF-alpha) were quantified. Differences among
platelet, leukocyte, and growth factor concentration were compared among the
different systems. Correlations between platelet and anabolic growth factor
concentrations were assessed. Subsequently, PRP was made from 12 additional dogs
using one of the devices. Each PRP was divided into three aliquots that were
activated with calcium chloride (CaCl2), human gamma-thrombin (HGT), or not
activated. Expression of CD62P and platelet-bound fibrinogen (CAP1) was
quantified for each activation group. Concentrations of TGF-beta1, PDGF-BB, and
TNF-alpha were also quantified for each activation group and a fourth group that
was frozen/thawed. Differences among activation groups were assessed by a
Friedman test. RESULTS: There were statistically significant differences among
the PRPs made with difference devices with regard to platelet, leukocyte, TGF
beta1, and PDGF-BB concentrations (p < 0.0001). There were weak to moderate
correlations (R2 = 0.07-0.58) between platelet and anabolic growth factor
concentrations but it appeared that activation had a greater effect on growth
factor concentration than did cellular composition. Intentional platelet
activation significantly increased CD62P and CAP1 expression as well as TGF-beta1
and PDGF-BB concentrations in the one PRP in which all activation methods were
assessed. Activation with HGT resulted in the greatest platelet activation, and
CaCl2 and freeze/thaw elicited moderate increases in either growth factor release
or CD62P and CAP1 expression. CONCLUSION: There are positive correlations between
platelet and anabolic growth factor concentrations in canine PRPs. However,
intentional platelet activation has a greater effect on growth factor delivery
than platelet concentration. Thrombin provides more robust activation than CaCl2.
PMID- 28424778
TI - Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and
Respiratory Syndrome across Different Regions and Production Systems of the US.
AB - Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most
impactful disease for the North American swine industry, due to its known
considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors
and reports weekly new PRRS cases in 766 sow herds across the US. The time
dependent reproduction number (TD-R) is a measure of a pathogen's
transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at
the regional and system levels. The primary objective of the study here was to
estimate the TD-R values for PRRSV using regional and system-level PRRS data, and
to contrast it with commonly used metrics of disease, such as incidence estimates
and space-time clusters. The second objective was to test whether the estimated
TD-Rs were homogenous across four US regions. Retrospective monthly incidence
data (2009-2016) were available from the SHMP. The dataset was divided into four
regions based on location of participants, and demographic and environmental
features, namely, South East (North Carolina), Upper Midwest East (UME,
Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma
panhandle). Generation time distributions were fit to incidence data for each
region, and used to calculate the TD-Rs. The Kruskal-Wallis test was used to
determine whether the median TD-Rs differed across the four areas. Furthermore,
we used a space-time permutation model to assess spatial-temporal patterns for
the four regions. Results showed TD-Rs were right skewed with median values close
to "1" across all regions, confirming that PRRS has an overall endemic nature.
Variation in the TD-R patterns was noted across regions and production systems.
Statistically significant periods of PRRSV spread (TD-R > 1) were identified for
all regions except UME. A minimum of three space-time clusters were detected for
all regions considering the time period examined herein; and their overlap with
"spreader events" identified by the TD-R method varied according to region. TD-Rs
may help to measure PRRS spread to understand, in quantitative terms, disease
spread, and, ultimately, support the design, implementation, and monitoring of
interventions aimed at mitigating the impact of PRRSV spread in the US.
PMID- 28424779
TI - The Effectiveness of Various Salacca Vinegars as Therapeutic Agent for Management
of Hyperglycemia and Dyslipidemia on Diabetic Rats.
AB - The aim of this study was to explore the potency of salacca vinegar made from
various Indonesian salacca fruit extracts as therapeutic agent for hyperglycemia
and dyslipidemia for STZ-induced diabetic rats. The rats were grouped into
untreated rats, STZ-induced diabetic rats without treatment, and STZ-induced
diabetic rats treated with Pondoh salacca vinegar, Swaru salacca vinegar, Gula
Pasir salacca vinegar, Madu salacca vinegar, or Madura salacca vinegar. Parameter
observed included blood glucose, total cholesterol (TC), high density lipoprotein
(HDL), low density lipoprotein (LDL), triglyceride (TG), malondialdehyde (MDA),
superoxide dismutase (SOD), and pancreas histopathology of the samples. The
results demonstrated that all salacca vinegars were capable of reducing blood
sugar (from 25.1 to 62%) and reducing LDL (from 9.5 to 14.8 mg/dL), TG (from 58.3
to 69.5 mg/dL), MDA (from 1.1 to 2.2 mg/dL), and TC (from 56.3 to 70.5 mg/dL) as
well as increasing HDL blood sugar of STZ-induced diabetic Wistar rats (from 52.3
to 60 mg/dL). Various salacca vinegars were also capable of regenerating
pancreatic cells. Nevertheless, the ability of Swaru salacca vinegar to manage
hyperglycemia and dyslipidemia appeared to be superior to other salacca vinegars.
Swaru salacca vinegar is a potential therapeutic agent to manage hyperglycemia
and dyslipidemia of STZ-induced diabetic rats.
PMID- 28424780
TI - Corrigendum to "Influence of a 10-Day Mimic of Our Ancient Lifestyle on
Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of
Origin"".
AB - [This corrects the article DOI: 10.1155/2016/6935123.].
PMID- 28424781
TI - Postembedding Decalcification of Mineralized Tissue Sections Preserves the
Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals.
AB - Bone histology of decalcified or undecalcified samples depends on the
investigation. However, in research each method provides different information to
answer the scientific question. Decalcification is the first step after sample
fixation and governs what analysis is later feasible on the sections. Besides,
decalcification is favored for immunostaining and in situ hybridization.
Otherwise, sample decalcification can be damaging to bone biomaterials implants
that contains calcium or strontium. On the other hand, after decalcification
mineralization cannot be assessed using histology or imaging mass spectrometry.
The current study provides a solution to the hardship caused by material presence
within the bone tissue. The protocol presents a possibility of gaining sequential
and alternating decalcified and undecalcified sections from the same bone sample.
In this manner, investigations using histology, protein signaling, in situ
hybridization, and mass spectrometry on the same sample can better answer the
intended research question. Indeed, decalcification of sections and grindings
resulted in well-preserved sample and biomaterials integrity. Immunostaining was
comparable to that of classically decalcified samples. The study offers a novel
approach that incites correlative analysis on the same sample and reduces the
number of processed samples whether clinical biopsies or experimental animals.
PMID- 28424782
TI - Clinical Significance of Preoperative Albumin and Globulin Ratio in Patients with
Gastric Cancer Undergoing Treatment.
AB - Background. The pretreatment albumin and globulin ratio (AGR) was an inflammation
associated factor which was related to the overall survival in various
malignancies. The aim of this study was to evaluate the prognostic value of AGR
in patients with gastric cancer. Method. This retrospective study included 862
cases pathologically diagnosed with gastric cancer. All patients were randomly
divided into the testing group (431 cases) and validation group (431 cases). The
relationships of AGR with clinicopathologic characteristics and prognosis were
analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing
group, the median overall survival was 26.90 months and the cutoff value of AGR
was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was
correlated with poorer overall survival. Multivariate analysis demonstrated that
AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI
= 0.351-0.973, and p = 0.039). In the validation group, the median overall
survival was 24.10 months. Lower AGR (<=1.50) also had a significantly poorer
overall survival by Kaplan-Meier analysis. According to multivariate analysis,
the AGR was also confirmed to be an independent prognostic factor for overall
survival (HR: 0.578, 95% CI = 0.373-0.897, and p = 0.015). Conclusions. Our study
suggested that the pretreatment AGR could be a prognostic biomarker for overall
survival in patients with gastric cancer.
PMID- 28424783
TI - Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP
alpha and PPAR-gamma Expression in 3T3-L1 Adipocytes.
AB - Many studies have comprehensively examined the venom of Ophiophagus hannah snake.
Its venom comprises different compounds exhibiting a wide range of
pharmacological activities. In this investigation, four peptide fractions (PFs),
ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O.
hannah were separated by HPLC and investigated for their inhibitory activity on
adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further
purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two
peptides on 3T3-L1 adipocytes, it was revealed that, at 10 MUg/mL, pOh2 was able
to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without
affecting cell viability. Furthermore, the pOh2 downregulated the gene expression
of important transcription factors C/EBP-alpha and PPAR-gamma. In addition, aP2
and GPDH adipocyte-specific markers were also significantly reduced compared to
untreated differentiated cells. Taken together, pOh2 inhibited the expression of
key transcription factors C/EBP-alpha and PPAR-gamma and their target genes, aP2
and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this
novel class of peptide might have potential for in vivo antiobesity effects.
PMID- 28424784
TI - Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected
to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation.
AB - Connexin 43 (Cx43) is the major component protein in astrocytic gap junction
communication. Recent studies have shown the cellular processes of gap junction
internalization and degradation, but many details remain unknown. This study
investigated the distribution of Cx43 and its mechanism after ischemic insult.
Astrocyte culture system and a model of ischemia/reperfusion (IR) or oxygen
glucose deprivation and reoxygenation (OGDR) were established. Cx43 distribution
was observed by laser scanning confocal microscopy under different cultivation
conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and
MAPRE1 (microtubule-associated protein RP/EB family member 1) expression at
different time points. The total number of Cx43 was unchanged in the normal and
IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were
significantly greater than that of the normal group. Particles in the cytoplasm
were significantly fewer after endocytosis was blocked by dynasore. There was no
difference among the groups at each time point regarding protein or gene
expression of MAPRE1. We concluded that internalization of Cx43 into the
cytoplasm occurred during ischemia, which was partially mediated through
endocytosis, not by the change of Cx43 quantity. Moreover, internalization was
not related to microtubule transport.
PMID- 28424785
TI - The Impact of Homocysteine, Vitamin B12, and Vitamin D Levels on Functional
Outcome after First-Ever Ischaemic Stroke.
AB - We explored the relationship between acute ischaemic stroke (IS) early functional
outcome and serum levels of homocysteine, vitamin B12, and D in a
noninterventional prospective clinical study. We enrolled 50 patients with first
ever IS and performed laboratory tests and functional assessment at three time
points: on admission and three and six months after stroke. Modified Rankin Scale
(mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all
participants by trained examiner blinded to laboratory data. Patients did not
receive treatment that might alter laboratory data. Admission NIHSS correlated
with homocysteine levels (r = 0.304, p < 0.05), B12 level (r = -0.410, p < 0.01),
and vitamin D levels (r = -0.465, p < 0.01). Functional outcome measures (BI and
mRS) did not significantly correlate with homocysteine and vitamin D3 levels at 3
and 6 months. However, a positive correlation with vitamin B12 levels was
detected for BI both at 3 and 6 months and mRS at 6 months. Higher serum vitamin
B12 levels were associated with better functional outcome at follow-up.
PMID- 28424786
TI - Immunocytochemistry Improving the Diagnosis of Trichomonas vaginalis Infections.
AB - The aim of this study was to evaluate the immunocytochemistry (ICC) to diagnose
trichomoniasis, particularly asymptomatic infections. By culture serial
dilutions, ICC was able to detect 1 trophozoite/mL, while the culture was
positive up to 100 trophozoites/mL. The ICC in vivo detection capability was
assessed in vaginal secretions of mice experimentally infected and in vaginal
swabs from asymptomatic HIV-positive pregnant women compared with culture. All
vaginal secretion samples from mice were positive according to both methods.
Swabs from fifty-five asymptomatic women were positive in four (7.27%) of them by
culture. Beyond these four, another ten (25.45%) women were positive by
immunocytochemistry, proving their higher sensitivity (p = 0.002), noticing 3.5
times more positives. ICC had better performance in both successive dilutions as
in asymptomatic women, showing higher sensitivity and specificity. In this way,
its facility of execution and cost-effectiveness support its practicality, as a
routine procedure to diagnose trichomoniasis not only when the parasite load is
lower but probably in all clinical scenarios.
PMID- 28424787
TI - Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System
Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei
Jianpi Formula in Treating COPD.
AB - In previous work, we identified 145 active compounds from Bufei Jianpi formula
(BJF) by system pharmacology and found that BJF showed short-term effect on
chronic obstructive pulmonary disease (COPD) rats. Here, we applied the
transcriptomic, proteomic, and metabolomics approaches to illustrate the long
term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD
effect through decreasing inflammatory cytokines level, preventing protease
antiprotease imbalance and collagen deposition on week 32 by continuous oral
administration to rats from weeks 9 to 20. Subsequently, applying the
transcriptomic, proteomic, and metabolomics techniques, we detected a number of
regulated genes, proteins, and metabolites, mainly related to antioxidant
activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF
treated rats. Afterwards, we integrated system pharmacology target, transcript,
protein, and metabolite data sets and found that many genes, proteins, and
metabolites in rats BJF-treated group and the target proteins of BJF were mainly
attributed to lipid metabolism, inflammatory response, oxidative stress, and
focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably
by system regulation of the lipid metabolism, inflammatory response pathways
oxidative stress, and focal adhesion.
PMID- 28424788
TI - Fully Automated Robust System to Detect Retinal Edema, Central Serous
Chorioretinopathy, and Age Related Macular Degeneration from Optical Coherence
Tomography Images.
AB - Maculopathy is the excessive damage to macula that leads to blindness. It mostly
occurs due to retinal edema (RE), central serous chorioretinopathy (CSCR), or age
related macular degeneration (ARMD). Optical coherence tomography (OCT) imaging
is the latest eye testing technique that can detect these syndromes in early
stages. Many researchers have used OCT images to detect retinal abnormalities.
However, to the best of our knowledge, no research that presents a fully
automated system to detect all of these macular syndromes is reported. This paper
presents the world's first ever decision support system to automatically detect
RE, CSCR, and ARMD retinal pathologies and healthy retina from OCT images. The
automated disease diagnosis in our proposed system is based on multilayered
support vector machines (SVM) classifier trained on 40 labeled OCT scans (10
healthy, 10 RE, 10 CSCR, and 10 ARMD). After training, SVM forms an accurate
decision about the type of retinal pathology using 9 extracted features. We have
tested our proposed system on 2819 OCT scans (1437 healthy, 640 RE, and 742 CSCR)
of 502 patients from two different datasets and our proposed system correctly
diagnosed 2817/2819 subjects with the accuracy, sensitivity, and specificity
ratings of 99.92%, 100%, and 99.86%, respectively.
PMID- 28424789
TI - Cognitive-Behavioral Coping, Illness Perception, and Family Adaptability in
Oncological Patients with a Family History of Cancer.
AB - Aim. The study investigated the differences between patients with and without a
family history of cancer regarding coping strategies, illness perception, and
family adaptability to the disease. Material and Methods. A total of 124 patients
diagnosed with cancer were included in the research (55 of them with a family
history of cancer). The Cognitive Emotion Regulation Questionnaire, the Strategic
Approach to Coping Scale, the Family Adaptability and Cohesion Scale, and the
Illness Perception Questionnaire were applied. The data were processed using the
SPSS 21 software. Results. Patients with previous records of cancer in the family
get significantly higher scores for the illness coherence factor. Family
satisfaction is significantly higher for patients with a genetic risk, compared
to the one reported by patients who suffer from the disease but have no genetic
risk. Cognitive-behavioral coping strategies and family cohesion are factors that
correlate with an adaptive perception of the illness in the case of patients with
a family history of cancer. Conclusion. Results are important for the
construction of strategies used for patients with a family history of cancer.
PMID- 28424790
TI - Development of Isothermal Recombinase Polymerase Amplification Assay for Rapid
Detection of Porcine Circovirus Type 2.
AB - Porcine circovirus virus type II (PCV2) is the etiology of postweaning
multisystemic wasting syndrome (PMWS), porcine dermatitis, nephropathy syndrome
(PDNS), and necrotizing pneumonia. Rapid diagnosis tool for detection of PCV2
plays an important role in the disease control and eradication program.
Recombinase polymerase amplification (RPA) assays using a real-time fluorescent
detection (PCV2 real-time RPA assay) and RPA combined with lateral flow dipstick
(PCV2 RPA LFD assay) were developed targeting the PCV2 ORF2 gene. The results
showed that the sensitivity of the PCV2 real-time RPA assay was 102 copies per
reaction within 20 min at 37 degrees C and the PCV2 RPA LFD assay had a detection
limit of 102 copies per reaction in less than 20 min at 37 degrees C. Both assays
were highly specific for PCV2, with no cross-reactions with porcine circovirus
virus type 1, foot-and-mouth disease virus, pseudorabies virus, porcine
parvovirus, porcine reproductive and respiratory syndrome virus, and classical
swine fever virus. Therefore, the RPA assays provide a novel alternative for
simple, sensitive, and specific identification of PCV2.
PMID- 28424791
TI - Antifatigue Effects of Antrodia cinnamomea Cultured Mycelium via Modulation of
Oxidative Stress Signaling in a Mouse Model.
AB - Antrodia cinnamomea, a folk medicinal mushroom, has numerous biological effects.
In this study, we aim to assess whether the antifatigue effects of A. cinnamomea
mycelia (AC) and its underlying mechanisms are related to oxidative stress
signaling using behavioral mouse models and biochemical indices detection. Mice
were orally treated with AC at doses of 0.1, 0.3, and 0.9 g/kg for three weeks.
AC had no effect on the spontaneous activities of mice indicating its safety on
central nervous system. Furthermore, results obtained from weight-loaded forced
swimming test, rotary rod test, and exhausted running test confirmed that AC
significantly enhanced exercise tolerance of mice. Biochemical indices levels
showed that these effects were closely correlated with inhibiting the depletion
of glycogen and adenosine triphosphate stores, regulating oxidative stress
related parameters (superoxide dismutase, glutathione peroxidase, reactive oxygen
species, and malondialdehyde) in serum, skeletal muscle, and liver of mice.
Moreover, the effects of AC may be related with its regulation on the activations
of AMP-activated protein kinase, protein kinase B, and mammalian target of
rapamycin in liver and skeletal muscle of mice. Altogether, our data suggest that
the antifatigue properties of AC may be one such modulation mechanism via
oxidative stress-related signaling in mice.
PMID- 28424793
TI - A Model-Based Meta-Analysis Evaluating Gender Differences on Blood Flow Responses
to Brachial Artery Infusions of Acetylcholine, Albuterol, ATP, Bradykinin,
Estradiol, Glyceryl Trinitrate, L-NMMA, Nevibolol, Norepinephrine, Sodium
Nitroprusside, Substance P, and Verapamil.
AB - INTRODUCTION: Numerous studies have emerged over the course of several decades
describing the properties of drugs eliciting vasodilatory or vasoconstrictor
responses in the human vasculature. During drug development, decisions to move
forward with testing with a new chemical entity are very costly. To fund or not
to fund development, go or no-go, decisions are often limited by efficacy
comparisons with the current products on the market. The primary aim of this
paper is to use dose-response modeling and simulations to quantify differences in
blood flow to Acetylcholine, Albuterol, ATP, Bradykinin, 17beta-Estradiol,
Glyceryl Trinitrate, L-NMMA, Nevibolol, Norepinephrine, Sodium Nitroprusside,
Substance P, and Verapamil. METHODS: Five studies were identified in the
literature that included a total of 12 compounds. Infusion doses were normalized
to nmol/min and forearm blood flow values were normalized and scaled to the
percent increase or decrease in forearm blood flow from baseline resting values.
The original published studies were mathematically modeled using the Emax model
or Sigmoid Emax model equation parameters. Lastly, dose-response simulations of
higher doses using a virtual population were produced to account for population
variability. RESULTS: The gender difference between the Emax estimates,
interpreted as the %Change from Baseline resting forearm blood flow, were found
to be: Albuterol 253%, Acetylcholine 231%, Substance P 159%, Verapamil 145%,
Bradykinin 42%, Sodium Nitroprusside 41%, and Glyceryl Trinitrate 26%.
Contrastingly, Norepinephrine and L-NMMA Emax gender difference resulted in a 6%
and 7% difference, respectively. CONCLUSION: These results provide insight into
the differences in men and women seen in anti-hypertensive patient management.
Further, the modeling estimates provide pharmacometricians evaluating new
compounds with mathematical parameters for comparative efficacy studies through
the various phases of drug development.
PMID- 28424792
TI - Sustained High Levels of Both Total and High Molecular Weight Adiponectin in
Plasma during the Convalescent Phase of Haemorrhagic Fever with Renal Syndrome
Are Associated with Disease Severity.
AB - Haemorrhagic fever with renal syndrome (HFRS) is characterised by an uncontrolled
immune response that causes vascular leakage. Adiponectin (APN) is an
adipocytokine involved in prorevascularisation and immunomodulation. To
investigate the possible effects of APN in the pathogenesis of HFRS, total and
high molecular weight (HMW) APN levels in the plasma of patients with HFRS were
quantified using enzyme-linked immunosorbent assay (ELISA). Compared with those
in healthy controls, the plasma total and HMW APN levels in patients were
elevated to different degrees from the fever onset and remained high at the
convalescent phase. Consistent with these results, western blot analysis
additionally showed that low molecular weight (LMW), middle molecular weight
(MMW), and HMW APN levels were all elevated and contributed to the elevation of
the total APN level. Importantly, sustained high levels of total and HMW APN at
the convalescent phase were significantly higher in patients with critical
disease than those in patients with mild or moderate disease. Moreover, total and
HMW APN levels negatively correlated with white blood cell count and positively
correlated with platelet count and serum albumin level. These results may provide
insights into understanding the roles of total and HMW APN in the pathogenesis of
HFRS.
PMID- 28424794
TI - Study design and baseline results of an open-label cluster randomized community
intervention trial to assess the effectiveness of a modified mass deworming
program in reducing hookworm infection in a tribal population in southern India.
AB - INTRODUCTION: Hookworm infection is a leading cause of iron deficiency anemia and
malnutrition in resource-poor settings. Periodic mass deworming with
anthelminthic drugs remains the cornerstone of hookworm control efforts
worldwide. Reinfection following treatment occurs, reflecting the human host's
inability to acquire immunity following exposure to an untreated reservoir of
infection. This cluster randomized trial will evaluate the effectiveness of a
modified, population-based, mass deworming strategy in reducing hookworm
infection in an endemic southern Indian population. METHODS: Forty five tribal
villages were randomized into three groups: one received annual treatment; the
second received two rounds of treatment at 1-month intervals; and the third
received four rounds of treatment - two rounds 1 month apart at the beginning,
followed by another two after 6 months. Stool samples collected through cross
sectional parasitological surveys pre- and post-intervention, and at 3-monthly
intervals for a period of 1 year were tested for presence of hookworm ova. Long
term effectiveness of treatment will be assessed through another survey conducted
2 years after the last treatment cycle. RESULTS: From a population of 11,857
individuals, 8681 (73.2%) were found to be eligible and consented to participate,
out-migration being the primary reason for non-participation. Baseline stool
samples were obtained from 2082 participants, with 18.5% having hookworm
infection, although majority were low intensity infections (<2000 eggs per gram
of feces). DISCUSSION: This study will help identify the optimal mass deworming
strategy that can achieve the greatest impact in the shortest period of time,
particularly in settings where long-term program sustainability is a challenge.
PMID- 28424795
TI - An open-label cluster randomised trial to evaluate the effectiveness of a
counselling intervention on linkage to care among HIV-infected patients in
Uganda: Study design.
AB - INTRODUCTION: Home-based HIV counselling & testing (HBHCT) is highly acceptable
and has the potential to increase HIV testing uptake in sub-Saharan Africa.
However, data are lacking on strategies that can effectively link HIV-positive
individuals identified through HBHCT to care. This trial was designed to assess
the effectiveness of two brief home-based counselling sessions on linkage to
care, provided subsequent to referral for care among HIV-positive patients
identified through HBHCT in a rural community in Masaka district, Uganda.
METHODS: 28 communities (clusters) were randomly allocated to control (referral
only) and intervention (referral and follow-up counselling) arms (n = 14
clusters/arm). Randomisation was stratified on distance from the district capital
(<=10 km vs > 10 km) and cluster size (larger single village vs combined small
villages), and restricted to ensure balance on selected cluster characteristics.
A list of possible allocations was generated and one randomly selected at a
public ceremony. HBHCT is being offered to all adults (>=18 years), and HIV
positive individuals not yet in care are eligible for enrolment. The intervention
is provided at one and two months post-enrolment. Primary outcomes, assessed 6
months after enrolment, are: the proportion of individuals linking to HIV care
within 6 months of HIV diagnosis and time to linkage. The primary analysis will
be based on individual-level data. DISCUSSION: This study will provide evidence
on the impact of a counselling intervention on linkage to care among adults
identified with HIV infection through HBHCT. Interpretation of the trial outcomes
will be aided by results from an on-going qualitative sub-study.
PMID- 28424796
TI - External data required timely response by the Trial Steering-Data Monitoring
Committee for the NALoxone InVEstigation (N-ALIVE) pilot trial.
AB - The prison-based N-ALIVE pilot trial had undertaken to notify the Research Ethics
Committee and participants if we had reason to believe that the N-ALIVE pilot
trial would not proceed to the main trial. In this paper, we describe how
external data for the third year of before/after evaluation from Scotland's
National Naloxone Programme, a related public health policy, were anticipated by
eliciting prior opinion about the Scottish results in the month prior to their
release as official statistics. We summarise how deliberations by the N-ALIVE
Trial Steering-Data Monitoring Committee (TS-DMC) on N-ALIVE's own interim data,
together with those on naloxone-on-release (NOR) from Scotland, led to the
decision to cease randomization in the N-ALIVE pilot trial and recommend to local
Principal Investigators that NOR be offered to already-randomized prisoners who
had not yet been released.
PMID- 28424798
TI - Hospital Readmissions - Independent Predictors of 30-day Readmissions derived
from a 10 year Database.
AB - Unplanned medical 30 day readmissions place a burden on the provision of acute
hospital services and are increasingly used as quality indicators to assess
quality of care in hospitals. Multivariable logistic regression of a 10 year
database showed that four factors were most strongly associated with early
readmission: Charlson comorbidity index >=1, respiratory disease as a principal
diagnosis, liver disease and alcohol-related illness as an additional diagnosis,
and the number of previous readmissions. Disease and patient-related factors
beyond control of the hospital are the factors most strongly associated with 30
day readmission to hospital, suggesting that this may not be an appropriate
quality indicator.
PMID- 28424799
TI - Role of Psychological Resilience on Health-Outcomes in Hospitalized Patients with
Acute Illness: A Scoping Review.
AB - Recovery from Acute Illness is dependent on severity of illness. We aimed to
investigate whether resilience as the 'ability to bounce back' might also affect
recovery. We conducted a scoping review to identify gaps in the existing
literature. We used emergency care, intensive care, critical care and trauma as
surrogates for acute illness. We mapped synonyms for resilience and selected
'resilience' and 'robustness'. The search was limited to adult patients admitted
to hospitals. We found strong evidence for psychological sequelae of acute
illness but no research focusing specifically on the concepts of resilience or
robustness and no interventional studies in the acute hospital setting. The
concept of resilience might be applicable to unscheduled admissions to hospital.
Measurements and potential interventions require further research.
PMID- 28424800
TI - Progressing care in the Medical High Dependency Unit: unit configurations,
staffing, standards, and daily routine.
AB - There are currently various models of care for provision of high dependency care
for acutely ill medical patients across the UK. Acute Physicians are integral to
the development and progression of this both challenging and rewarding area of
medicine. This article outlines current standards, best evidence, and our own
experience of both setting up and developing a medical high dependency unit
(MHDU).
PMID- 28424797
TI - Magnetoencephalography as a Tool in Psychiatric Research: Current Status and
Perspective.
AB - The application of neuroimaging to provide mechanistic insights into circuit
dysfunctions in major psychiatric conditions and the development of biomarkers
are core challenges in current psychiatric research. We propose that recent
technological and analytic advances in magnetoencephalography (MEG), a technique
that allows measurement of neuronal events directly and noninvasively with
millisecond resolution, provides novel opportunities to address these fundamental
questions. Because of its potential in delineating normal and abnormal brain
dynamics, we propose that MEG provides a crucial tool to advance our
understanding of pathophysiological mechanisms of major neuropsychiatric
conditions, such as schizophrenia, autism spectrum disorders, and the dementias.
We summarize the mechanisms underlying the generation of MEG signals and the
tools available to reconstruct generators and underlying networks using advanced
source-reconstruction techniques. We then surveyed recent studies that have used
MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This was
followed by links with preclinical research that has highlighted possible
neurobiological mechanisms, such as disturbances in excitation/inhibition
parameters, that could account for measured changes in neural oscillations.
Finally, we discuss challenges as well as novel methodological developments that
could pave the way for widespread application of MEG in translational research
with the aim of developing biomarkers for early detection and diagnosis.
PMID- 28424801
TI - Problem-based review: Immune-mediated complications of 'Checkpoint Inhibitors'
for the Acute Physician.
AB - Immunotherapy with 'checkpoint-inhibitors' has significantly improved outcomes
for patients with a range of malignancies. However, significant immune-mediated
toxicities of these therapies are well-described. These immune-mediated
toxicities can affect virtually all organ systems and are potentially fatal. The
timing of onset of the adverse effects is dependent on the organ system affected
and can occur after completion of the treatment. The increasing utilisation of
'checkpoint-inhibitors' means that Acute Physicians are likely to see a number of
immune-mediated complications presenting to the AMU. The fundamental principles
of management of immune-mediated toxicities are early recognition, supportive
treatment, escalating steroid therapy (dependent on the severity of the
toxicity), close liaison with Oncology and specialist organ team input. Research
into the optimal strategies and pathways for the management of immune-mediated
toxicity, as well as increased collaboration between Acute Physicians and
Oncologists, will be necessary.
PMID- 28424802
TI - Evolving sepsis definitions and their impact on Acute Medical Units.
AB - BACKGROUND: There are currently several different definitions for sepsis. This
study looked at what proportion of acute medical admissions were identified by
the different definitions, what correlation they have, and how many patients
would require a review with results in 1 hour. METHODS: Data on 212 admissions
was collected, on time of admission and review, and number of patients with
sepsis by each diagnostic criteria calculated. RESULTS: The NICE criteria
identified 69% of admissions as requiring review within one hour, compared to 6%
with qSOFA and 18% with previous sepsis definitions. The mean time to review was
1hr 18min, and only 50% of patients meeting the NICE criteria were reviewed
within one hour. CONCLUSIONS: The proposed NICE guidance will be challenging to
implement with current resources.
PMID- 28424803
TI - Use of a flumazenil infusion to treat chlordiazepoxide toxicity.
AB - "Alcohol detox" is a common presentation to acute medical services and is usually
managed via standardised guidelines and protocols. We present a case of
chlordiazepoxide toxicity, requiring repeated bolus doses and subsequently 24
hours of an intravenous infusion of flumazenil in response to guideline directed
management of an alcohol withdrawal state. The use of prolonged flumazenil
infusions to treat benzodiazepine toxicity is infrequently described.
Chlordiazepoxide is metabolised in the hepatic microsomal pathway and hepatic
impairment can lead to accumulation of toxic metabolites, which may have been the
explanation for toxicity in this case. In patients at risk of liver dysfunction
we advise the use of benzodiazepines not requiring phase 1 oxidative metabolism,
such as lorazepam or oxazepam.
PMID- 28424804
TI - Acute Medicine Finishing School: Preparing for the next step.
AB - The transition from registrar to consultant in medicine is one that trainees feel
ill prepared for and can be extremely stressful. We devised the concept of an
Acute Medicine "Finishing School" for senior trainees in London training
programmes and ran sessions on CV writing, a simulated consultant interview,
consultant job planning, responding to complaints and an out of hospital
emergency scenario. Our feedback survey indicated that our delegates' confidence
levels in all of the above aspects increased following the sessions. Both formal
and informal feedback highlighted the need and appetite for such a course. By
ensuring trainees are trained and supported through this transition process, we
can ensure the process is a less stressful one.
PMID- 28424805
TI - Cruising through the journey without getting drowned: The saga of a PhD student
in the Netherlands.
AB - Young medical trainees all over the world are encouraged to investigate unknown
areas of medicine that need clarification. This often leads them to undertake a
PhD (Doctor of Philosophy). Being curious, critical, and creative are necessary
competences which enable us to engender scientific research within acute
(internal) medicine. Worldwide, huge numbers of professionals are pursuing a PhD,
with the aim of receiving a 'Doctor'-title. These PhD trajectories vary
distinctly between countries. Since the distances in the scientific world are
getting smaller and it is becoming more easy to work with each other across
borders, it might be interesting to know what it requires to become an academic
'doctor' overseas. Hereby, we provide a concise insight in to the differences
between doing PhD in (acute) medicine in the Netherlands and in the UK.
PMID- 28424818
TI - Dose requirements for idarucizumab reversal of dabigatran in a lethal porcine
trauma model with continuous bleeding.
AB - Idarucizumab is licensed for emergency reversal of dabigatran. A single 5 g dose
is usually sufficient, but higher doses may sometimes be required and optimum
dosing has not been defined. It was the aim of this study to investigate the
effect of idarucizumab, given once or as a split dose, after double trauma in
pigs anticoagulated with dabigatran. Dabigatran etexilate (30 mg/kg bid) was
given to 18 male pigs orally for 3 days. On day 4, animals were randomised 1:1:1
to receive idarucizumab 60+0, 60+60 or 120+0 mg/kg. Doses were administered 15
and 75 minutes after initial liver trauma. At 60 minutes, a second liver injury
was undertaken. Animals were monitored for 5 hours after initial trauma or until
death. Blood loss during the first hour was 990 +/- 109 ml, 988 +/- 84 ml and 964
+/- 75 ml in the 60+0, 60+60 and 120+0 groups, respectively. In the 120+0 and
60+60 groups, total blood loss was 1659 +/- 346 and 1426 +/- 106 ml,
respectively, and survival at 5 hours was 100 %. However, in the 60+0 group,
total blood loss was 3561 +/- 770 ml and survival was 50 %. Analysis of
dabigatran plasma concentrations showed that equimolar concentrations of
idarucizumab are necessary to bind all dabigatran and achieve sufficient thrombin
generation. At sufficient doses, idarucizumab rapidly reduced blood loss and
improved survival in this lethal porcine model of double trauma with dabigatran
anticoagulation. In clinical practice, should bleeding continue after initial
treatment with the approved 5 g dose of idarucizumab, a second dose may
potentially be effective to control bleeding caused by redistribution of unbound
dabigatran.
PMID- 28424819
TI - Plasma microRNAs characterising patients with immune thrombocytopenic purpura.
AB - Altered microRNA (miRNA) expression has been reported in patients with immune
thrombocytopenic purpura (ITP). However, the detailed expression profiling of
cell-free circulating miRNAs in ITP patients has not been fully investigated. In
this study, we aimed to examine plasma miRNAs in ITP patients and evaluate their
diagnostic values. Plasma samples from 74 ITP patients and 58 healthy controls
were obtained and allocated into discovery, validation, and therapy-response
sets. Initial screen with a miRNA microarray assay identified 23 miRNAs with
different levels between ITP patients and healthy controls (>1.5-fold changes;
p<0.01). Subsequent quantitative real-time PCR confirmed eight up-regulated
miRNAs (miR-320c, miR-642b-3p, miR-1275, miR-3141, miR-4270, miR-4499, miR-4739
and miR-6126) and three down-regulated miRNAs (miR-144-3p, miR-1281 and miR-3162
3p) in ITP patients. The levels of these circulating miRNAs varied, depending on
ITP subtypes, i.e. newly-diagnosed, persistent and chronic ITP, and between
treatment responders and non-responders. In receiver operator characteristic
analysis, 10 miRNAs had positive diagnostic values (p<0.05) when tested
individually. The diagnostic value improved when the miRNAs were analysed as a
panel or together with the analysis of anti-platelet autoantibodies. Plasma miR
3162-3p levels were also found to positively correlate with platelet counts in
ITP patients (r=0.338, p=0.01). Our results indicate that plasma miRNA profiles
are altered in ITP patients and that the differentially expressed miRNAs may be
used as biomarkers to improve the diagnosis of ITP.
PMID- 28424820
TI - Microparticles during long-term follow-up after acute myocardial infarction.
Association to atherosclerotic burden and risk of cardiovascular events.
AB - Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs)
and monocytes (MMPs), and in acute myocardial infarction (MI), there is an
increase of MPs in the culprit artery. In this study MPs were evaluated in whole
blood in 105 patients with MI at five time-points during a two-year follow-up
(FU). Patients with non-ST-elevated MI had higher concentrations of CD41+MPs
compared to ST-elevated MI patients (p=0.024). The concentrations of PMPs in
whole blood increased during the time period (p<0.001), but no significant change
over time was found for EMPs and MMPs. CD62P+MP counts were higher in MI patients
with diabetes (p=0.020), and patients with hypertension had increased levels of
CD14+MPs (p=0.004). The amount of CD62P+TF+MPs increased significantly during FU
(p<0.001). Patients with atherosclerosis in three arterial beds, i. e. coronary,
carotid and peripheral arteries, had lower concentrations of CD62P+TF+MPs
(p=0.035) and CD144+TF+MPs (p=0.004) compared to patients with atherosclerosis in
one or two arterial beds. Higher concentrations of CD62P+MPs early after MI were
associated with an increased risk of cardiovascular events during FU, hazard
ratio 3.32 (95 %CI1.20-9.31). Only small variations in PMP, EMP and MMP
concentrations were found during long-term FU after MI and their levels seem to
reflect the underlying cardiovascular disease rather than the acute MI. PMPs
expressing P-selectin might be a promising biomarker for predicting future
cardiovascular events, but further studies are needed to confirm these results.
PMID- 28424821
TI - NOACs for treatment of venous thromboembolism in clinical practice.
AB - Randomised controlled trials have provided important information on the efficacy
and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) for
treatment of venous thromboembolism (VTE), leading to registration and increasing
use in clinical practice. Many questions remain to be answered, and observational
studies are often more suitable for answering "real-world" questions than
randomised controlled trials. Patient satisfaction, quality of life, and
adherence and persistence in clinical practice with the drug regimen can only be
assessed with an open-label design. Evaluation of risk for long-term sequelae of
the disease requires much longer follow-up than is possible in registration
trials. Treatment patterns and utilisation of health care resources can be
assessed from observations in the clinical practice setting. We will review
published as well as currently active observational studies with NOACs in VTE,
with or without a comparator anticoagulant. These studies are based on cohorts of
different sizes, registries, or administrative health care databases. We will
also discuss some limitations in analysis and interpretation of observational
studies.
PMID- 28424822
TI - Rapid non-contrast magnetic resonance imaging for post appendectomy intra
abdominal abscess in children.
AB - BACKGROUND: Acute appendicitis, especially if perforated at presentation, is
often complicated by postoperative abscess formation. The detection of a
postoperative abscess relies primarily on imaging. This has traditionally been
done with contrast-enhanced computed tomography. Non-contrast magnetic resonance
imaging (MRI) has the potential to accurately detect intra-abdominal abscesses,
especially with the use of diffusion-weighted imaging (DWI). OBJECTIVE: To
evaluate our single-center experience with a rapid non-contrast MRI protocol
evaluating post-appendectomy abscesses in children with persistent postsurgical
symptoms. MATERIALS AND METHODS: In this retrospective, institutional review
board-approved study, all patients underwent a clinically indicated non-contrast
1.5- or 3-Tesla abdomen/pelvis MRI consisting of single-shot fast spin echo,
inversion recovery and DWI sequences. All MRI studies were reviewed by two
blinded pediatric radiologists to identify the presence of a drainable fluid
collection. Each fluid collection was further characterized as accessible or not
accessible for percutaneous or transrectal drainage. Imaging findings were
compared to clinical outcome. RESULTS: Seven of the 15 patients had a clinically
significant fluid collection, and 5 of these patients were treated with
percutaneous drain placement or exploratory laparotomy. The other patients had a
phlegmon or a clinically insignificant fluid collection and were discharged home
within 48 h. CONCLUSION: Rapid non-contrast MRI utilizing fluid-sensitive and DWI
sequences can be used to identify drainable fluid collections in post
appendectomy patients. This protocol can be used to triage patients between
conservative management vs. abscess drainage without oral/intravenous contrast or
exposure to ionizing radiation.
PMID- 28424823
TI - [Coma in the emergency room].
AB - Coma of unknown origin (CUO) is a frequent unspecific emergency symptom
associated with a high mortality. A fast diagnostic work-up is essential given
the wide spectrum of underlying diagnoses that are made up of approximately 50%
primary central nervous system (CNS) pathologies and approximately 50%
extracerebral, almost exclusively internal medical causes. Despite the high
mortality associated with this symptom, there are currently no generally accepted
management guidelines for adult patients presenting with CUO. We propose an
interdisciplinary standard operating procedure (SOP) for patients with acute CUO
as has been established in our maximum care hospital. The SOP is triggered by
simple triage criteria that are sufficient to identify CUO patients before
arrival in hospital. The in-hospital response team is led by a neurologist.
Collaboration with nursing staff, internal medicine, anesthesiology, neurosurgery
and trauma surgery is organized along structured pathways that include
standardized laboratory tests, including cerebrospinal fluid (CSF), toxicology,
computed tomography (CT) and CT angiography imaging (CTA). Our data suggest that
neurologists and internists need to be placed at the beginning of the diagnostic
work-up. Imaging should not just be carried out depending on the clinical
syndrome because sensitivity, specificity and inter-rater reliability of the
latter are not sufficient and because in many cases, multiple pathologies can be
detected that could each explain CUO alone. Clinical examination, imaging and
laboratory testing should be regarded as components of an integrative diagnostic
approach and the final aetiological classification should only be made after the
diagnostic work-up is complete.
PMID- 28424824
TI - Resistin and NGAL are associated with inflammatory response, endothelial
activation and clinical outcomes in sepsis.
AB - OBJECTIVE AND DESIGN: Resistin and neutrophil gelatinase-associated lipocalin
(NGAL) are upregulated in circulating leucocytes in sepsis, but the significance
of this is uncertain. We evaluated associations between Resistin and NGAL with
endothelial cell activation and clinical outcomes in a prospective observational
study in the Emergency Department (ED). METHODS: Serum levels of Resistin, NGAL,
inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules
(VCAM-1, ICAM-1) were measured at defined time points up to 24 h. Patterns and
relationships between markers were investigated using linear mixed regression
models. Predictive values for clinical outcomes for markers at enrollment were
assessed by logistic regression and receiver operator characteristic (ROC)
curves. RESULTS: 186 participants (89 septic-shock, 69 sepsis, 28 uncomplicated
infection) were compared with 29 healthy controls. Median Resistin and NGAL were
higher in uncomplicated infection compared to controls, and in septic shock
compared to non-shock sepsis. Resistin and NGAL correlated with IL-6 and IL-10,
with VCAM-1 and ICAM-1, and with organ failure. Resistin and NGAL were associated
with septic shock but had limited predictive utility for mortality. CONCLUSION:
Resistin and NGAL correlate with expression of endothelial cell adhesion
molecules in sepsis. Further evaluation of the role of Resistin and NGAL in
sepsis pathogenesis is warranted.
PMID- 28424825
TI - A Magnetized Nanoparticle Based Solid-Phase Extraction Procedure Followed by
Inductively Coupled Plasma Atomic Emission Spectrometry to Determine Arsenic,
Lead and Cadmium in Water, Milk, Indian Rice and Red Tea.
AB - A sensitive and simple method using magnetic multi-walled carbon nanotube (MWCNTs
Fe3O4 MNP), as the adsorbent, has been successfully developed for extraction and
pre-concentration of arsenic, lead and cadmium with detection by inductively
coupled plasma-atomic emission spectroscopy (ICP-AES). The nanosorbent was
characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray
diffraction pattern (XRD), vibrating sample magnetometer (VSM) and transmission
electron microscopy (TEM). The key factors affecting the signal intensity such as
pH, adsorbent amount, etc. were investigated. Under optimal conditions, the
limits of detection (three-time of signal to noise ratio, S/N 3) were 0.3, 0.6,
0.3 ng/mL for arsenic, lead and cadmium, respectively. Application of the
adsorbent was investigated by the analysis of water, milk, Indian rice and red
tea. The experimental data was analyzed and obeyed Langmuir and Freundlich
adsorption models. The kinetic data was fitted to the pseudo-second-order model.
Thermodynamic studies revealed the feasibility and exothermic nature of the
system.
PMID- 28424826
TI - Synergizing 13C Metabolic Flux Analysis and Metabolic Engineering for Biochemical
Production.
AB - Metabolic engineering of industrial microorganisms to produce chemicals, fuels,
and drugs has attracted increasing interest as it provides an environment
friendly and renewable route that does not depend on depleting petroleum sources.
However, the microbial metabolism is so complex that metabolic engineering
efforts often have difficulty in achieving a satisfactory yield, titer, or
productivity of the target chemical. To overcome this challenge, 13C Metabolic
Flux Analysis (13C-MFA) has been developed to investigate rigorously the cell
metabolism and quantify the carbon flux distribution in central metabolic
pathways. In the past decade, 13C-MFA has been widely used in academic labs and
the biotechnology industry to pinpoint the key issues related to microbial-based
chemical production and to guide the development of the appropriate metabolic
engineering strategies for improving the biochemical production. In this chapter
we introduce the basics of 13C-MFA and illustrate how 13C-MFA has been applied to
synergize with metabolic engineering to identify and tackle the rate-limiting
steps in biochemical production.
PMID- 28424828
TI - [On the treatment of candiduria and nitroxoline sensitivity of Candida isolates].
PMID- 28424827
TI - Fluorescence Spectroscopy for the Monitoring of Food Processes.
AB - Different analytical techniques have been used to examine the complexity of food
samples. Among them, fluorescence spectroscopy cannot be ignored in developing
rapid and non-invasive analytical methodologies. It is one of the most sensitive
spectroscopic approaches employed in identification, classification,
authentication, quantification, and optimization of different parameters during
food handling, processing, and storage and uses different chemometric tools.
Chemometrics helps to retrieve useful information from spectral data utilized in
the characterization of food samples. This contribution discusses in detail the
potential of fluorescence spectroscopy of different foods, such as dairy, meat,
fish, eggs, edible oil, cereals, fruit, vegetables, etc., for qualitative and
quantitative analysis with different chemometric approaches.
PMID- 28424829
TI - [MRI of the prostate].
AB - New clinical and technological advances in the field of magnetic resonance
imaging (MRI) and targeted image-guided biopsy techniques have significantly
improved the detection, localization and staging as well as active surveillance
of prostate cancer in recent years. Multiparametric MRI (mpMRI) is currently the
main imaging technique for the detection, characterization and diagnostics of
metastasizing prostate cancer and is of high diagnostic importance for local
staging within the framework of the detection of prostate cancer.
PMID- 28424830
TI - [When is a nonsurgical approach possible for metastatic primary tumors and lymph
node metastases of the urinary bladder and prostate?]
AB - For metastatic carcinomas of the urinary bladder and prostate, systemic therapy
is of primary importance. Due to technological advances in radiation oncology
such as stereotactic radiotherapy, intensity-modulated radiotherapy, interstitial
radiotherapy, and the combination of radiotherapy and chemotherapy, pelvic
irradiation can nowadays be carried out effectively and without the risk of major
side effects. New data from other tumor entities and retrospective analyses
suggest that the use of these technologies can lead to a clinical benefit in
terms of improvement in quality of life, local control, and overall survival. For
the time being, the decision to administer radiotherapy to the pelvic region
should be made on an individual basis. Retrospective analyses of data from
prostate carcinomas in particular are currently being planned. This review
article introduces potential indications which are supported with real patient
examples and discusses future developments giving an overview of the literature
and referring to data from prospective randomized trials.
PMID- 28424831
TI - [Recurrent and catheter-associated urinary tract infections : Prophylaxis and
prevention].
AB - Urinay tract infection (UTI) as one of the most frequent bacterial infections in
humans is of utmost relevance. Because of the rising prevalence of antimicrobial
resistance, urinalysis should always include urine culture and a resistogram in
order to avoid an unspecific selection and overuse of antibiotics. Prevention of
recurrent UTI must first of all rule out predisposing uropathogenic conditions.
Nowadays, a great variety of drugs, behavioral, and supportive treatment options
can effectively minimize UTI recurrence. The growing importance of vaccines
(immunotherapy), probiotics (lactobacilli), and standardized herbal preparations
meets the need of reducing antibiotic use and the development of antimicrobial
resistance. Around 80% of all nosocomial UTIs (nUTIs) are associated with
indwelling urinary catheters. It is estimated that up to 70% of all nUTIs
occurring in Germany may be avoided by using appropriate preventative measures.
Therefore, profound knowledge about the basics of catheter-associated nUTIs and
the correct management of urinary catheters are of utmost individual and
socioeconomic importance.
PMID- 28424832
TI - Setting up a community-based cervical screening service in a low-income country:
a pilot study from north-western Tanzania.
AB - OBJECTIVES: To report the results of a pilot study for a service for cervical
cancer screening and diagnosis in north-western Tanzania. METHODS: The pilot
study was launched in 2012 after a community-level information campaign. Women
aged 15-64 years were encouraged to attend the district health centres. Attendees
were offered a conventional Pap smear and a visual inspection of the cervix with
acetic acid (VIA). RESULTS: The first 2500 women were evaluated. A total of 164
women (detection rate 70.0/1000) were diagnosed with high-grade cervical
intraepithelial neoplasia and invasive cervical cancer. The performance of VIA
was comparable to that of Pap smear. The district of residence, a history of
untreated sexually transmitted disease, an HIV-negative status (inverse
association), and parity were independently associated with the detected
prevalence of disease. The probability of invasive versus preinvasive disease was
lower in HIV-positive women and in women practicing breast self-examination.
CONCLUSIONS: The diagnostic procedure had an acceptable level of quality. Factors
associated with the detected prevalence of disease will allow for a more targeted
promotion of the service. Cervical screening should be coordinated with sexually
transmitted disease and HIV infection control activities.
PMID- 28424833
TI - Cannabis-related hippocampal volumetric abnormalities specific to subregions in
dependent users.
AB - RATIONALE: Cannabis use is associated with neuroanatomical alterations in the
hippocampus. While the hippocampus is composed of multiple subregions, their
differential vulnerability to cannabis dependence remains unknown. OBJECTIVES:
The objective of the study is to investigate gray matter alteration in each of
the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields
CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence.
METHODS: A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and
39 dependent (CB-dep) cannabis users were recruited. We investigated group
differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep
users. We further explored the association between CB use variables (age of onset
of regular use, monthly use, lifetime use) and hippocampal subregions in CB
nondep and CB-dep users separately. RESULTS: The CA1, CA2/3, CA4/DG, as well as
total hippocampal gray matter were reduced in volume in CB-dep but not in CB
nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also
negatively associated with lifetime cannabis use in CB-dep users. CONCLUSIONS:
Our results suggest a regionally and dependence-specific influence of cannabis
use on the hippocampus. Hippocampal alteration in cannabis users was specific to
the CA and DG regions and confined to dependent users.
PMID- 28424834
TI - Effect of prior foot shock stress and Delta9-tetrahydrocannabinol, cannabidiolic
acid, and cannabidiol on anxiety-like responding in the light-dark emergence test
in rats.
AB - RATIONALE: Cannabis is commonly used by humans to relieve stress. OBJECTIVES AND
METHODS: Here, we evaluate the potential of intraperitoneally (i.p.) administered
Delta9-tetrahydrocannabiol (THC) and cannabidiolic acid (CBDA, the precursor of
cannabidiol [CBD]) to produce dose-dependent effects on anxiety-like responding
in the light-dark (LD) emergence test of anxiety-like responding in rats, when
administered acutely or chronically (21 days). As well, we evaluate the potential
of THC, CBDA, and CBD to reduce anxiogenic responding produced by foot shock (FS)
stress 24 h prior to the LD test. RESULTS: In the absence of the explicit FS
stressor, THC (1 and 10 mg/kg) produced anxiogenic-like responding when
administered acutely or chronically, but CBDA produced neither anxiogenic- nor
anxiolytic-like responding. Administration of FS stress 24 h prior to the LD test
enhanced anxiogenic-like responding (reduced time spent and increased latency to
enter the light compartment) in rats pretreated with either vehicle (VEH) or THC
(1 mg/kg); however, administration of CBDA (0.1-100 MUg/kg) or CBD (5 mg/kg)
prevented the FS-induced anxiogenic-like responding (an anxiolytic-like effect).
The 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist, WAY100635, reversed
CBDA's anxiolytic effect (1 MUg/kg). Combining an anxiolytic dose of CBDA (1
MUg/kg) or CBD (5 mg/kg) with an anxiogenic dose of THC (1 mg/kg) did not modify
THC's anxiogenic effect. CONCLUSION: These results suggest the anxiolytic effects
of CBDA and CBD may require the presence of a specific stressor.
PMID- 28424835
TI - [Future of emergency medicine in Germany 2.0].
AB - In 2003 an article on the future of prehospital emergency medicine in Germany was
published in the journal Der Anaesthesist. Emergency medicine in Germany, which
at that time was almost exclusively defined as prehospital emergency rescue, has
evolved and now in-hospital domains have increasingly moved into the focus. At
that time, the primary goal was to connect prehospital management with a smooth
transition to hospital admission and further care in the hospital and to further
optimize the rescue chain from the actual emergency through to causative
treatment. Now after 15 years, the authors have critically assessed the
development postulated in 2003 and reevaluated it. Which aspects could be
developed further and become firmly established, what is still open and which
questions in preclinical and clinical emergency treatment of the population will
occupy us in the coming 15 years? With a critical eye to the past, the present
contribution aims to capture the essential and new topics and open questions and
provide a fresh perspective for the future of emergency medicine. Regulation at
the state level or even lower levels of government often stand in contrast to
more sweeping and economically effective approaches at the federal level.
Prehospital emergency medicine in Germany is on the whole well-positioned with
respect to facilities and personnel; however, as far as the economic situation
and the utilization of available systems are concerned, there is still
substantial room for improvement.
PMID- 28424836
TI - [On the occasion of Swen Malte John's 60th birthday].
PMID- 28424837
TI - Arsenic, Cadmium, Chromium, Lead, Mercury and Selenium Concentrations in Pine
Snakes (Pituophis melanoleucus) from the New Jersey Pine Barrens.
AB - Top trophic level predators are at risk from bioaccumulation of heavy metals from
their prey. Using nondestructively collected tissues as a method of assessing
metal concentrations in snakes is useful for populations that are threatened or
declining. This paper reports concentrations of arsenic (As), cadmium (Cd),
chromium (Cr), lead (Pb), mercury (Hg), and selenium (Se) in tissues of Northern
pine snakes (Pituophis melanoleucus) from the New Jersey Pine Barrens, a
relatively pristine, undisturbed habitat. We also determined if skin is an
appropriate indicator of internal concentrations and identified the factors
(tissue, year of collection, length, sex) that might explain variations in metal
concentrations. Because they can grow to 2-m long and live for 25 years, we
suggest that these snakes might accumulate heavy metals. Multiple regression
models were significant, explaining 16% (lead) to 61% (mercury) of variation by
tissue type. For mercury and chromium, size also was significant. The highest
concentrations were in liver and kidney for all metals, except chromium and lead.
Mercury concentrations in tissues were within the range reported for other snakes
and were below effects concentrations in reptiles. The concentrations in skin
were correlated with all internal tissues for mercury and for all internal
tissues except heart for cadmium. These data show that shed skin can be used as
an indicator of metals in pine snakes and that, at present, concentrations of
heavy metals in this population are within the range of those found in other
snake species from uncontaminated sites.
PMID- 28424838
TI - Improved oncologic outcome with chemoradiotherapy followed by surgery in
unresectable intrahepatic cholangiocarcinoma.
AB - PURPOSE: To investigate the ability of chemoradiotherapy (CRT) to down-stage
unresectable intrahepatic cholangiocarcinoma (IHCC) to resectable lesions, as
well as the factors associated with achieving such down-staging. METHODS: The
study cohort comprised 120 patients diagnosed with stage I-IVA IHCC between 2001
and 2012. Of these patients, 56 underwent surgery and 64 received CRT as their
initial treatment. The rate of curative resections for patients who received CRT
was assessed, and the locoregional failure-free survival (LRFFS) and overall
survival (OS) rates of these patients were compared to those of patients who
underwent CRT alone. RESULTS: Median follow-up was 36 months. A partial response
after CRT was observed in 25% of patients, whereas a biologic response (a >70%
decrease of CA19-9) was observed in 35%. Eight patients (12.5%) received curative
resection after CRT and showed significantly improved LRFFS and OS compared to
those treated with CRT alone (3-year LRFFS: 50 vs. 15.7%, respectively, p = 0.03;
3-year OS: 50 vs. 11.2%, respectively, p = 0.012); these rates were comparable to
those of patients who received initial surgery. Factors associated with curative
surgery after CRT were gemcitabine administration, higher radiotherapy dose
(biological effective dose >=55 Gy with alpha/beta = 10), and a >70% reduction of
CA19-9. CONCLUSION: Upfront CRT could produce favorable outcomes by converting
unresectable lesions to resectable tumors in selected patients. Higher
radiotherapy doses and gemcitabine-based chemotherapy yielded a significant
reduction of CA19-9 after CRT; patients with these characteristics had a greater
chance of curative resection and improved OS.
PMID- 28424839
TI - Reirradiation of recurrent node-positive non-small cell lung cancer after
previous stereotactic radiotherapy for stage I disease : A multi-institutional
treatment recommendation.
AB - BACKGROUND: Practice guidelines have been developed for early-stage and locally
advanced non-small cell lung cancer (NSCLC). However, many common clinical
scenarios still require individualized decision making. This is true for
locoregional relapse after initial stereotactic radiotherapy (stereotactic body
radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an
increasingly utilized curative treatment option for stage I NSCLC. METHODS: A
consortium of expert radiation oncologists was established with the aim of
providing treatment recommendations. In this scenario, a case was distributed to
six radiation oncologists who provided their institutions' treatment
recommendations. In this case, a patient developed local and mediastinal relapse
after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage
IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion
was developed. RESULTS: Three institutions recommended evaluation for surgery. If
the patient was not a surgical candidate, and/or refused surgery, definitive
chemoradiation was recommended, including retreating the primary to full dose.
European participants were more in favor of a non-surgical approach. None of the
participants were reluctant to prescribe reirradiation, but two institutions
prescribed doses lower than 60 Gy. Platinum-based doublets together with
intensity-modulated radiotherapy were preferred. CONCLUSION: The institutional
recommendations reflect the questions and uncertainties discussed in current
stage III guidelines. All institutions agreed that previous SABR is not a
contraindication for salvage chemoradiation. In the absence of high-quality
prospective trials for recurrent NSCLC, all treatment options recommended in
current guidelines for stage III disease can be considered in clinical scenarios
such as this.
PMID- 28424840
TI - Reirradiation for recurrent head and neck cancers using charged particle or
photon radiotherapy.
AB - OBJECTIVE: To examine the outcomes of reirradiation for recurrent head and neck
cancers using different modalities. METHODS: This retrospective study included 26
patients who received charged particle radiotherapy (CP) and 150 who received
photon radiotherapy (117 CyberKnife radiotherapy [CK] and 36 intensity-modulated
radiotherapy [IMRT]). Inverse probability of treatment weighting (IPTW) involving
propensity scores was used to reduce background selection bias. RESULTS: Higher
prescribed doses were used in CP than photon radiotherapy. The 1-year overall
survival (OS) rates were 67.9% for CP and 54.1% for photon radiotherapy (p =
0.15; 55% for CK and 51% for IMRT). In multivariate Cox regression, the
significant prognostic factors for better survival were nasopharyngeal cancer,
higher prescribed dose, and lower tumor volume. IPTW showed a statistically
significant difference between CP and photon radiotherapy (p = 0.04). The local
control rates for patients treated with CP and photon radiotherapy at 1 year were
66.9% (range 46.3-87.5%) and 67.1% (range 58.3-75.9%), respectively. A total of
48 patients (27%) experienced toxicity grade >=3 (24% in the photon radiotherapy
group and 46% in the CP group), including 17 patients with grade 5 toxicity.
Multivariate analysis revealed that younger age and a larger planning target
volume (PTV) were significant risk factors for grade 3 or worse toxicity.
CONCLUSION: CP provided superior survival outcome compared to photon
radiotherapy. Tumor volume, primary site (nasopharyngeal), and prescribed dose
were identified as survival factors. Younger patients with a larger PTV
experienced toxicity grade >=3.
PMID- 28424841
TI - Dosimetric predictors of radiation-induced pericardial effusion in esophageal
cancer.
AB - PURPOSE: To evaluate the dose-volume parameters of the pericardium and heart in
order to reduce the risk of radiation-induced pericardial effusion (PE) and
symptomatic PE (SPE) in esophageal cancer patients treated with concurrent
chemoradiotherapy. METHODS: In 86 of 303 esophageal cancer patients, follow-up CT
was obtained at least 24 months after concurrent chemoradiotherapy. Correlations
between clinical factors, including risk factors for cardiac disease, dosimetric
factors, and the incidence of PE and SPE after radiotherapy were analyzed using
Cox proportional hazard regression analysis. Significant dosimetric factors with
the highest hazard ratios were investigated using zones separated according to
their distance from esophagus. RESULTS: PE developed in 49 patients. Univariate
analysis showed the mean heart dose, heart V5-V55, mean pericardium dose, and
pericardium V5-V50 to all significantly affect the incidence of PE. Additionally,
body surface area was correlated with the incidence of PE in multivariate
analysis. Grade 3 and 4 SPE developed in 5 patients. The pericardium V50 and
pericardium D10 significantly affected the incidence of SPE. The pericardium V50
in patients with SPE ranged from 17.1 to 21.7%. Factors affecting the incidence
of SPE were the V50 of the pericardium zones within 3 cm and 4 cm of the
esophagus. CONCLUSION: A wide range of radiation doses to the heart and
pericardium were related to the incidence of PE. A pericardium V50 <= 17% is
important to avoid symptomatic PE in esophageal cancer patients treated with
concurrent chemoradiotherapy.
PMID- 28424842
TI - WY-14643 and 9-cis-retinoic acid induce IRS-2/PI 3-kinase signalling pathway and
increase glucose transport in human skeletal muscle cells: differential effect in
myotubes from healthy subjects and Type 2 diabetic patients.
AB - AIMS/HYPOTHESIS: To determine the effects of peroxisome proliferator-activated
receptor alpha (PPARalpha) and retinoid X receptor (RXR) agonists on insulin
action, we investigated the effects of Wy-14643 and 9-cis-retinoic acid (9-cis
RA) on insulin signalling and glucose uptake in human myotubes. METHODS: Primary
cultures of differentiated human skeletal muscle cells, established from healthy
subjects and Type 2 diabetic patients, were used to study the effects of Wy-14643
and 9-cis-RA on the expression and activity of proteins involved in the insulin
signalling cascade. Glucose transport was assessed by measuring the rate of [3H]2
deoxyglucose uptake. RESULTS: Wy-14643 and 9-cis-RA increased IRS-2 and p85alpha
phosphatidylinositol 3-kinase (PI 3-kinase) mRNA and protein expression in
myotubes from non-diabetic and Type 2 diabetic subjects. This resulted in
increased insulin stimulation of protein kinase B phosphorylation and increased
glucose uptake in cells from control subjects. Myotubes from diabetic patients
displayed marked alterations in the stimulation by insulin of the IRS-1/PI 3
kinase pathway. These alterations were associated with blunted stimulation of
glucose transport. Treatment with Wy-14643 and 9-cis-RA did not restore these
defects but increased the basal rate of glucose uptake.
CONCLUSIONS/INTERPRETATION: These results demonstrate that PPARalpha and RXR
agonists can directly affect insulin signalling in human muscle cells. They also
indicate that an increase in the IRS-2/PI 3-kinase pathway does not overcome the
impaired stimulation of the IRS-1-dependent pathway and does not restore insulin
stimulated glucose uptake in myotubes from Type 2 diabetic patients.
PMID- 28424843
TI - EASD News Section July 2004.
PMID- 28424844
TI - Microbial reductive dehalogenation of trihalomethanes by a Dehalobacter
containing co-culture.
AB - Trihalomethanes such as chloroform and bromoform, although well-known as a
prominent class of disinfection by-products, are ubiquitously distributed in the
environment due to widespread industrial usage in the past decades. Chloroform
and bromoform are particularly concerning, of high concentrations detected and
with long half-lives up to several hundred days in soils and groundwater. In this
study, we report a Dehalobacter- and Desulfovibrio-containing co-culture that
exhibits dehalogenation of chloroform (~0.61 mM) to dichloromethane and bromoform
(~0.67 mM) to dibromomethane within 10-15 days. This co-culture was further found
to dechlorinate 1,1,1-trichloroethane (1,1,1-TCA) (~0.65 mM) to 1,1
dichloroethane within 12 days. The Dehalobacter species present in this co
culture, designated Dehalobacter sp. THM1, was found to couple growth with
dehalogenation of chloroform, bromoform, and 1,1,1-TCA. Strain THM1 harbors a
newly identified reductive dehalogenase (RDase), ThmA, which catalyzes
chloroform, bromoform, and 1,1,1-TCA dehalogenation. Additionally, based on the
sequences of thmA and other identified chloroform RDase genes, ctrA, cfrA, and
tmrA, a pair of chloroform RDase gene-specific primers were designed and
successfully applied to investigate the chloroform dechlorinating potential of
microbial communities. The comparative analysis of chloroform RDases with
tetrachloroethene RDases suggests a possible approach in predicting the substrate
specificity of uncharacterized RDases in the future.
PMID- 28424845
TI - The regulatory role of the transcription factor Crz1 in stress tolerance,
pathogenicity, and its target gene expression in Metarhizium acridum.
AB - In fungi, the Ca2+/calcineurin signaling pathway is critical in mediating growth,
morphology, stress responses, and pathogenicity. Crz1 is a calcineurin-responsive
zinc finger transcription factor. Here, MaCrz1 was identified and functionally
characterized in the entomopathogenic fungus Metarhizium acridum by
characterization of a targeted gene knockout strain. Conidia of the DeltaMacrz1
mutant were aberrant in cell surface features and lacked the characteristic
hydrophobic rodlet layer, and the mutant displayed increased sensitivity to
oxidative stress, cell wall perturbing agents, heat stress, and ultraviolet
irradiation as compared to the wild-type and complemented strains. Insect
bioassay using locusts revealed decreased virulence for the DeltaMaCrz1 mutant,
with defects in the ability of the mutant to penetrate the host cuticle. The
DeltaMaCrz1 mutant also showed greatly reduced chitin and beta-1,3-glucan level
in the cell wall. Transcriptomic profiling revealed genes involved in cell wall
synthesis, conidiation, stress tolerance, and calcium transport that were
downregulated in the DeltaMaCrz1 mutant. Our results demonstrate that MaCrz1
plays important roles in stress susceptibility and pathogenicity, and provides
clues as to the genes and pathways targeted by the transcription factor.
PMID- 28424846
TI - Summary of the preservation techniques and the evolution of the anammox bacteria
characteristics during preservation.
AB - The anaerobic ammonium oxidation (anammox) process is a promising wastewater
treatment method for biological nitrogen removal. A sufficient amount of active
anammox sludge as a seed is crucial to the fast establishment and stability of
the anammox process. Anammox bacteria is a kind of microorganism which is
sensitive to the environmental conditions, e.g., oxygen, temperature. The optimum
temperature and pH for the growth of the anammox bacteria are 30-40 degrees C
and 6.7-8.3. A proper preservation technique allows fast start-up of the anammox
process, overcoming the long doubling time of anammox biomass. The preservation
of the anammox sludge is influenced by various factors, e.g., preservation
techniques, duration, temperature, substrates, and protective agents. During
preservation, the characteristics of the anammox biomass, including the
bioactivity, heme c content, extracellular polymeric substances (EPS), and sludge
morphology, change with time. The optimum preservation technique is not
invariable and it depends on the purpose of preservation (precedence of
bioactivity or quantity), the bacterial community, and other parameters. It is
important for the preserved anammox biomass to achieve reactivation so that
stable anammox reactors can be established as soon as possible. However, because
the preservation process is complicated, the knowledge regarding preservation is
far from complete, and much future work will be required to increase the
understanding of preservation.
PMID- 28424847
TI - Characterization of microtubule buckling in living cells.
AB - Microtubules are filamentous biopolymers involved in essential biological
processes. They form key structures in eukaryotic cells, and thus it is very
important to determine the mechanisms involved in the formation and maintenance
of the microtubule network. Microtubule bucklings are transient and localized
events commonly observed in living cells and characterized by a fast bending and
its posterior relaxation. Active forces provided by molecular motors have been
indicated as responsible for most of these rapid deformations. However, the
factors that control the shape amplitude and the time scales of the rising and
release stages remain unexplored. In this work, we study microtubule buckling in
living cells using Xenopus laevis melanophores as a model system. We tracked
single fluorescent microtubules from high temporal resolution (0.3-2 s) confocal
movies. We recovered the center coordinates of the filaments with 10-nm precision
and analyzed the amplitude of the deformation as a function of time. Using
numerical simulations, we explored different force mechanisms resulting in
microtubule bending. The simulated events reproduce many features observed for
microtubules, suggesting that a mechanistic model captures the essential
processes underlying microtubule buckling. Also, we studied the interplay between
actively transported vesicles and the microtubule network using a two-color
technique. Our results suggest that microtubules may affect transport indirectly
besides serving as tracks of motor-driven organelles. For example, they could
obstruct organelles at microtubule intersections or push them during filament
mechanical relaxation.
PMID- 28424848
TI - Glycemic control, mortality, secondary infection, and hypoglycemia in critically
ill pediatric patients: a systematic review and network meta-analysis of
randomized controlled trials.
PMID- 28424849
TI - Ultrasound evaluation of the ulnar collateral ligament of the elbow: Which method
is most reproducible?
AB - INTRODUCTION: The ulnar collateral ligament (UCL) is an important medial
stabilizer of the elbow, particularly in overhead-throwing athletes. However,
there is no universally accepted method for evaluating UCL thickness with
ultrasound (US). OBJECTIVE: To assess reproducibility of previously published
methods, as well as a modified technique, for evaluating the UCL via US. We
hypothesize that a modified technique would show greater reproducibility.
MATERIAL AND METHODS: Using US, the thickness of the UCL in 50 volunteers was
measured by two musculoskeletal trained radiologists using two different
measurement techniques. The techniques utilized were as described by Nazarian and
Jacobson/Ward (JW). Technique measurements were evaluated using interclass
correlation coefficients (ICC) to determine the reproducibility of each method.
Twenty-eight of the subjects also underwent measurement via a modified JW
technique, measured perpendicular to the ligament rather than the frame of
imaging. This technique was also evaluated with ICC values. RESULTS: The ICC
value for the Nazarian technique was 0.82 (very good) and 0.51 (moderate) for the
JW technique. When using the modified JW technique, we found an ICC value of 0.84
(very good). Mean ligament thickness was greatest with the Nazarian technique,
6.41 mm, with the JW technique measuring 1.86 mm and the modified technique
measuring 1.38 mm. CONCLUSION: US assessment of UCL thickness by all three
measurement techniques are reproducible. The JW technique had less interobserver
agreement when compared to the Nazarian method, whereas the modified JW technique
had greater reproducibility compared to the JW technique and similar to the
Nazarian technique.
PMID- 28424850
TI - Incidence and MRI characterization of the spectrum of posterolateral corner
injuries occurring in association with ACL rupture.
AB - OBJECTIVE: To determine the incidence and MRI characteristics of the spectrum of
posterolateral corner (PLC) injuries occurring in association with anterior
cruciate ligament (ACL) rupture. MATERIALS AND METHODS: We carried out a level
IV, retrospective case series study. All patients clinically diagnosed with an
ACL rupture between July 2015 and June 2016 who underwent MRI of the knee were
included in the study. In addition to standard MRI knee reporting, emphasis was
placed on identifying injury to the PLC and a description of involvement of these
structures by two musculoskeletal radiologists. Association with PLC involvement
was sought with concomitant injuries using correlation analysis and logistic
regression. RESULTS: One hundred sixty-two patients with MRI following ACL
rupture were evaluated. Thirty-two patients (19.7%) had an injury to at least one
structure of the PLC, including the inferior popliteomeniscal fascicle (n = 28),
arcuate ligament (n = 20), popliteus tendon (n = 20), superior popliteomeniscal
fascicle (n = 18), lateral collateral ligament (n = 8), popliteofibular ligament
(n = 7), biceps tendon (n = 4), iliotibial band (n = 3), and fabellofibular
ligament (n = 1). Seventy-five percent of all patients with combined ACL and PLC
injuries had bone contusions involving the lateral compartment of the knee. The
presence of these contusions strongly correlated with superior popliteomeniscal
fascicle lesions (p < 0.05). There was no correlation between injuries to other
structures of the PLC and other intra-articular lesions. CONCLUSION: Missed
injuries of the PLC lead to considerable morbidity. The relevance of this study
is to highlight that these injuries occur more frequently than previously
described and that an appropriate index of suspicion, clinical examination, and
MRI are all required to reduce the risk of missed diagnoses. The results of this
study support previous suggestions that the rate of concomitant PLC injury in the
ACL-deficient knee is under-reported. The rate of combined injuries in this
series was 19.7%. The key message of this paper is that PLC injury is common in
the presence of ACL injury and should be sought both clinically and
radiologically.
PMID- 28424851
TI - Vascularized fibular medialization for reconstruction of the tibial defects
following tumour excision.
AB - PURPOSE: The purpose of this study was to evaluate the functional and oncologic
results of fibular medialization when used alone as a single-stage reconstructive
technique after wide excision of malignant tumours of the proximal, middle, or
distal tibia. METHODS: Between December 2010 and May 2015, 14 patients (six males
and eight females) with primary malignant tumours of the tibia (eight proximal,
four diaphyseal, two distal) were treated by wide excision. The mean age of the
patients at the time of surgery was 23.2 years (11-38). The fibula was mobilized
medially with its vascular pedicle to fill the defect and was fixed by a long
plate and screws bypassing the graft. The average size of the defects
reconstructed was 19.5 cm (18-22). Patients were evaluated functionally using the
Musculoskeletal Tumour Society (MSTS) scoring system. RESULTS: The mean follow-up
period was 31.3 months (range, 17-54). The average time for complete union was
7.6 months (range, 6-9). At final follow-up all patients had fully united grafts;
11 walked without aids. Chest metastases developed in one patient, superficial
wound infection in two patients and leg length discrepancy in four patients; one
case had LLD of more than 3 cm. The mean MSTS score was 23/30 points (76.5%). The
minimum score was 40% (12/30) and the maximum was 90% (27/30). CONCLUSIONS:
Ipsilateral pedicled vascularized fibular centralisation or medialization is a
durable reconstruction for tibial defects after wide excision of bone tumours
with an acceptable functional outcome. Stable osteosynthesis is the key to union.
PMID- 28424852
TI - Clinical application of bone morphogenetic proteins for bone healing: a
systematic review.
AB - PURPOSE: This paper documents the existing evidence on bone morphogenetic
proteins (BMPs) use for the treatment of bone fractures, non-union, and
osteonecrosis, through a review of the clinical literature, underlying potential
and limitations in terms of cost effectiveness and risk of complications.
METHODS: A systematic review was performed on the PubMed database using the
following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone
regeneration) including papers from 2000 to 2016. The search focused on clinical
trials dealing with BMPs application to favor bone regeneration in bone
fractures, non-union, and osteonecrosis, in English language, with level of
evidence I, II, III, and IV. Relevant data (type of study, number of patients,
BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were
extracted and analyzed. RESULTS: Forty-four articles met the inclusion criteria:
10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series,
and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures,
and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found
among RCTs and comparative papers: 11 reported positive results for BMPs
augmentation, 3 obtained no significant effects, and 2 showed negative results.
The only study comparing the two BMPs showed a better outcome with rhBMP-2 for
non-union treatment. CONCLUSION: Clinical evidence on BMPs use for the treatment
of fractures, non-union, and osteonecrosis is still controversial, with the few
available reports being mainly of low quality. While positive findings have been
described in many studies, mixed results are still present in the literature in
terms of efficacy and adverse events. The difficulties in drawing clear
conclusions are also due to the studies heterogeneity, mainly in terms of
different BMPs applied, with different concomitant treatments for each bone
pathology. Therefore, further research with well-designed studies is needed in
order to understand the real potential of this biological approach to favour bone
healing.
PMID- 28424853
TI - Long-term results of ankle arthrodesis in children and adolescents with
haemophilia.
AB - INTRODUCTION: Ankle arthrodesis in patients with haemophilia is a joint-non
preserving treatment option often resulting in substantial pain relief and
termination of haemarthrosis by osseous consolidating of the joint. However,
limited data are available regarding ankle arthrodesis in young patients. AIM:
The aim of this study was to evaluate the long-term clinical and radiographic
results with a minimum follow-up of ten years in children with haemophilia who
underwent ankle arthrodesis. METHODS: We retrospectively reviewed the results of
ankle fusions performed in young haemophiliacs in our department between 1980 and
2006. The Meary procedure was used for arthrodesis, performed on patients with
closed growth plates. Only one patient had no fixation, due to being only six
years old. The modified American Orthopaedic Foot & Ankle Society (AOFAS)
hindfoot score was calculated at last follow-up, and standard radiographic
evaluations were performed. RESULTS: A total of 22 ankles were analysed from 17
patients. The mean follow-up was 19.7 +/- 8 years. The mean age of the patients
was 15.5 (6-23) years at the time of index surgery. There were no intra-operative
or peri-operative complications related to ankle arthrodesis. The mean modified
AOFAS score at last follow-up was 83 +/- 10.5. Radiographic assessment
demonstrated solid osseous fusion at the arthrodesis site, with no axis
deformities. Two patients developed secondary subtalar arthrosis, treated by
subtalar arthrodesis six years after initial ankle arthrodesis in one case.
CONCLUSION: In our study, tibiotalar arthrodesis in young patients with
haemophilia resulted in good long-term functional outcome with a low surgery
related complication rate.
PMID- 28424854
TI - The effectiveness of narrative enhancement and cognitive therapy: a randomized
controlled study of a self-stigma intervention.
AB - PURPOSE: Stigma has been proposed to be one of the most serious obstacles to
successful treatment, rehabilitation and inclusion in society of people with
severe mental illness. An aspect of stigma which has been increasingly discussed
is self-stigma, which refers to the internalization of negative stereotypes among
people with severe mental illness. The aim of the present study was to
investigate the effectiveness of a group-based anti self-stigma intervention,
narrative enhancement and cognitive therapy (NECT) as an add-on to treatment as
usual, with regard to changes in self-stigma, self-esteem, and subjective quality
of life. METHOD: After screening for eligibility 106 participants were included
in a randomized controlled trial using a wait-list control group, of which 87
completed the study. Assessments were made at baseline, at termination of the
intervention, and at a 6-month follow-up (intervention group only). RESULTS: The
results showed that NECT was effective in reducing self-stigma and improving self
esteem compared to treatment as usual only. No differences were shown regarding
subjective quality of life. Changes shown in the intervention group at
termination of intervention were stable at the 6-month follow-up. A regression
analysis showed that there was a positive relationship between exposure to the
intervention and reduction of self-stigma. CONCLUSIONS: The conclusion of the
present study is that, using a sample size with adequate power, NECT seems to be
an effective intervention with regard to diminishing self-stigma and improving
self-esteem, and that these improvements were stable at a 6-month follow-up.
There was a distinct relationship between number of sessions attended and
improvements in self-stigma and self-esteem controlling for confounding factors.
This puts attention to the importance of creating a group climate which
facilitate and encourage participation through the various phases of the
intervention.
PMID- 28424855
TI - Analysis of multiple soybean phytonutrients by near-infrared reflectance
spectroscopy.
AB - Improvement of the nutritional quality of soybean is usually facilitated by a
vast range of soybean germplasm with enough information about their multiple
phytonutrients. In order to acquire this essential information from a huge number
of soybean samples, a rapid analytic method is urgently required. Here, a
nondestructive near-infrared reflectance spectroscopy (NIRS) method was developed
for rapid and accurate measurement of 25 nutritional components in soybean
simultaneously, including fatty acids palmitic acid, stearic acid, oleic acid,
linoleic acid, and linolenic acid, vitamin E (VE), alpha-VE, gamma-VE, delta-VE,
saponins, isoflavonoids, and flavonoids. Modified partial least squares
regression and first, second, third, and fourth derivative transformation was
applied for the model development. The 1 minus variance ratio (1-VR) value of the
optimal model can reach between the highest 0.95 and lowest 0.64. The predicted
values of phytonutrients in soybean using NIRS technology are comparable to those
obtained from using the traditional spectrum or chemical methods. A robust NIRS
can be adopted as a reliable method to evaluate complex plant constituents for
screening large-scale samples of soybean germplasm resources or genetic
populations for improvement of nutritional qualities. Graphical Abstract ?.
PMID- 28424856
TI - Homogenous assay for protein detection based on proximity DNA hybridization and
isothermal circular strand displacement amplification reaction.
AB - This work proposed a homogenous fluorescence assay for proteins, based on the
target-triggered proximity DNA hybridization in combination with strand
displacement amplification (SDA). It benefited from target-triggered proximity
DNA hybridization to specifically recognize the target and SDA making recycling
signal amplification. The system included a molecular beacon (MB), an extended
probe (EP), and an assistant probe (AP), which were not self-assembly in the
absence of target proteins, due to the short length of the designed complementary
sequence among MB, EP, and AP. Upon addition of the target proteins, EP and AP
are bound to the target proteins, which induced the occurrence of proximity
hybridization between MB, EP, and AP and followed by strand displacement
amplification. Through the primer extension, a tripartite complex of probes and
target was displaced and recycled to hybridize with another MB, and the more
opened MB enabled the detection signal to amplify. Under optimum conditions, it
was used for the detection of streptavidin and thrombin. Fluorescence intensity
was proportional to the concentration of streptavidin and thrombin in the range
of 0.2-30 and 0.2-35 nmol/L, respectively. Furthermore, this fluorescent method
has a good selectivity, in which the fluorescence intensity of thrombin was ~37
fold or even larger than that of the other proteins at the same concentration. It
is a new and simple method for SDA-involved target protein detection and
possesses a great potential for other protein detection in the future. Graphical
abstract A homogenous assay for protein detection is based on proximity DNA
hybridization and strand displacement amplification reaction.
PMID- 28424857
TI - Extraction of cell-free DNA from urine, using polylysine-coated silica particles.
AB - DNA analysis is used for a variety of purposes, including disease diagnosis and
DNA profiling; this involves extracting DNA from living organisms. In this study,
we prepared polycationic silica particles to extract DNA that has the negatively
charged phosphate backbone from solution. The coated particles were prepared by
mixing conventional silica gel particles and poly-Lys; these particles could
efficiently extract 1.3 MUg of cell-free DNA from 50 mL of (male) urine. It is
expected that these easily prepared particles (just a mixture of two commercially
available chemicals) can be used as a noninvasive diagnostic tool for genetic
disorders such as cancer, diabetes, and hypertension. Graphical abstract
Effective extraction method of cfDNA from urine was developed that used
commercially available silica gel particles and poly-Lys.
PMID- 28424858
TI - Electrochemical simulation of biotransformation reactions of citrinin and
dihydroergocristine compared to UV irradiation and Fenton-like reaction.
AB - Mycotoxins occur widely in foodstuffs and cause a variety of mold-related health
risks to humans and animals. Elucidation of the metabolic fate of mycotoxins and
the growing number of newly discovered mycotoxins have enhanced the demand for
fast and reliable simulation methods. The viability of electrochemistry coupled
with mass spectrometry (EC/ESI-MS), Fenton-like oxidation, and UV irradiation for
the simulation of oxidative phase I metabolism of the mycotoxins citrinin (CIT)
and dihydroergocristine (DHEC) was investigated. The specific reaction products
are compared with metabolites produced by human and rat liver microsomes in
vitro. Depending on the applied potential between 0 and 2000 mV vs. Pd/H2 by
using a flow-through cell, CIT and DHEC are oxidized to various products. Besides
dehydrogenation and dealkylation reactions, several hydroxylated DHEC and CIT
species are produced by EC and Fenton-like reaction, separated and analyzed by LC
MS/MS and ESI-HRMS. Compared to reaction products from performed microsomal
incubations, several mono- and dihydroxylated DHEC species were found to be
similar to the reaction products of EC, Fenton-like reaction, and UV-induced
oxidation. Consequentially, nonmicrosomal efficient and economic simulation
techniques can be useful in early-stage metabolic studies, even if one-to-one
simulation is not always feasible.
PMID- 28424859
TI - Investigation of carbon-based nanomaterials as sorbents for headspace in-tube
extraction of polycyclic aromatic hydrocarbons.
AB - Carbon-based nanomaterials (CNM) represent promising materials for the
application as sorbents in micro- and other extraction devices. In this work, we
investigate the applicability of five different CNM (multi-walled carbon
nanotubes (MWCNTs), fullerenes, carboxylic acid functionalized multi-walled
carbon nanotubes (MWCNTs-COOH), graphene platelets, and carbon nanohorns) for
their performance on PAH extraction from the aqueous phase by headspace in-tube
extraction (HS-ITEX). Optimal extraction parameters for HS-ITEX were determined
using a Box-Behnken experimental design. From the extraction yield response,
central point analysis, fullerenes showed the best extraction properties for the
eight selected headspace compatible PAHs (naphthalene, acenaphthylene,
acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, and pyrene).
Fullerenes were used for a further method validation including the linear range,
limit of detection, precision, as well as recovery. Finally, extraction yields
were compared to a commercial material (Tenax GR), demonstrating that fullerene
represents a better option as sorbent in ITEX for PAH analysis. Method detection
limits for the PAH on fullerene ranged from 10 to 300 ng L-1, with recoveries
between 45 and 103%.
PMID- 28424860
TI - Influence of tibial hybrid fixation on graft tension and stability in ACL double
bundle reconstruction.
AB - PURPOSE: Initial graft tension in anterior cruciate ligament (ACL) reconstruction
affects stability and tension loss at follow-up. This study investigated the
influence of hybrid tibial fixation in 3-tunnel double-bundle ACL reconstruction
on initial graft tension and tension change and stability under anterior and
combined rotatory loads. METHODS: Eleven fresh-frozen cadaveric knees were
reconstructed with an ACL double bundle using a 3-tunnel technique. Grafts were
tightened to 80 N in 60 degrees (AM bundle) and 15 degrees (PL bundle) of
flexion. Anterior tibial translation under 134 N of anterior shear load and
translation under combined rotatory and valgus loads (10 Nm valgus stress, 4 Nm
internal tibial torque) were determined at 0 degrees , 30 degrees , 60 degrees ,
and 90 degrees flexion. In addition, graft tension under continuous passive
motion was determined. Intact, ACL-resected and ACL-reconstructed joints with
either tibial extracortical graft fixation or extracortical plus supplemental
aperture graft fixation (hybrid fixation) were tested. RESULTS: Hybrid fixation
did not increase graft tension in either bundle during fixation or in motion
without additional load. AM-bundle tension increased (p < 0.05) at 0 degrees
under combined rotatory and valgus loads and at 30 degrees and 60 degrees under
both loading conditions without decreasing the anterior tibial translation. PL
bundle tension increased (p < 0.05) only at 90 degrees under combined rotatory
and valgus loads. CONCLUSIONS: Tibial hybrid fixation in 3-tunnel double-bundle
ACL reconstruction increases time-zero AM- and PL-bundle tensions under loading
conditions, generating greater construct stiffness. This could lead to a longer
preservation of ACL-graft stability in clinical follow-up before bony
incorporation.
PMID- 28424861
TI - S -ketamine compared to etomidate during electroconvulsive therapy in major
depression.
AB - Objective of the study was to compare two commonly used anesthetic drugs, S
ketamine and etomidate, regarding their influence on seizure characteristics,
safety aspects, and outcome of electroconvulsive therapy (ECT) in major
depression. Treatment data of 60 patients who underwent a total number of 13 ECTs
(median) because of the severe or treatment-resistant major depressive disorder
(DSM-IV) were analyzed. Etomidate, mean dosage (SD) = 0.25 (0.04) mg/kg, was used
for anesthesia in 29 participants; 31 patients received S-ketamine, mean dosage
(SD) = 0.96 (0.26) mg/kg. Right unilateral brief pulse ECTs were performed. The
number of ECTs was individually adjusted to clinical needs, mean (SD) = 13.0
(4.3). Seizure characteristics, adverse events, and the clinical global
impression (CGI) scores were compared between the both groups during ECT series.
In the S-ketamine group, a lower initial seizure threshold (p = 0.014),
stimulation charge (p < 0.001), higher postictal suppression (p < 0.001), EEG
ictal amplitude (p = 0.04), EEG coherence (p < 0.001) and maximum heart rate (p =
0.015) were measured. Etomidate was associated with more frequent abortive
seizures (p = 0.02) and restimulations (p = 0.01). The CGI scores, the number of
sessions within an ECT series, and the incidence of adverse events did not differ
between groups. Due to its lower initial seizure threshold, S-ketamine might hold
a potential to become a clinically favorable anesthetic agent during ECT.
However, the current findings should be interpreted with caution, and further
prospective randomized clinical trials are required. Also, specific adverse
effects profile of S-ketamine, especially with regard to the cardiovascular risk,
needs to be taken into account.
PMID- 28424862
TI - Laparoscopic management of choledochal cysts: is a keyhole view missing the big
picture?
AB - In recent years, numerous articles have promoted laparoscopic surgical treatment
of choledochal cysts in children. Most of these reports assert that laparoscopic
excision and biliary reconstruction are as safe as open surgery and achieve
equivalent or better results. However, these conclusions are based on
retrospective analyses with median follow-up periods that rarely exceed 5 years.
Closer scrutiny of the laparoscopic literature indicates that the optimum
procedure for treating type I and most type IVa choledochal cysts, namely radical
excision of the extrahepatic bile ducts and reconstruction by wide hilar
hepaticoenterostomy, preferably hepaticojejunostomy, is not being carried out in
most cases. Performing a less radical excision exposes patients to a greater long
term risk of a bilioenteric stricture and its complications and malignant change
in residual extrahepatic bile ducts. Currently, the long-term outcomes of surgery
for choledochal cysts are being eclipsed by the short-term gains of laparoscopic
techniques. The prime objective in the surgical management of choledochal cysts
is the long-term health of the patient; laparoscopic techniques are simply
another method of performing the surgery and they should not become the standard
of care unless long-term outcomes are similar to best practice open surgery.
PMID- 28424863
TI - Current practice regarding timing of patent processus vaginalis ligation for
idiopathic hydrocele in young boys: a survey of UK surgeons.
AB - PURPOSE: The aim of this study was to determine the current UK practice regarding
timing of surgical repair of hydroceles in young boys. METHODS: Through a
validated, online survey, participants were asked their preferred management
option in five different clinical scenarios across five age ranges. RESULTS: 71
responses were included in the analysis. The most common age to offer surgical
intervention for a congenital hydrocele that is stable or increasing in size, or
a hydrocele of the cord is 24-36 months. For a stable hydrocele presenting after
12 months of age, the most common age to offer repair is between 36 and 48
months. Approximately 1/4 of respondents defer surgery until 4 years of age for
any stable hydrocele. For a congenital hydrocele that is decreasing in size, the
majority of respondents (57%) do not offer surgical intervention even over 4
years of age. The majority of respondents (61%) do not differentiate between
communicating and non-communicating hydroceles when considering age for repair.
CONCLUSION: These results suggest that there is uncertainty regarding the optimum
age for PPV ligation and adequate underlying variability in practice to support a
prospective study of the optimum age for hydrocele repair and the natural history
of PPV closure.
PMID- 28424864
TI - Loss of chromosome Y (LOY) in blood cells is associated with increased risk for
disease and mortality in aging men.
AB - Recent discoveries have shown that harboring cells without the Y chromosome in
the peripheral blood is associated with increased risk for all-cause mortality
and disease such as different forms of cancer, Alzheimer's disease, as well as
other conditions in aging men. In the entire world, the life expectancy of men is
shorter compared to women, a sex difference that has been known for centuries,
but the underlying mechanism(s) are not well understood. As a male-specific
genetic risk factor, an increased risk for pathology and mortality associated
with mosaic loss of chromosome Y (LOY) in blood cells could help to explain that
men on average live shorter lives compared to women. This review primarily
focuses on observed associations between LOY in blood and various diseases in
aging men. Other topics covered are known risk factors for LOY, methods to detect
LOY, and a discussion regarding mechanisms such as immunosurveillance, that could
possibly explain how an acquired mutation in blood cells can be associated with
disease processes in other organs.
PMID- 28424865
TI - Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological
diagnosis of congenital and acquired isolated hypoganglionosis.
AB - Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two
subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the
rarity of the disease and the lack of defining histological criteria, the concept
of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens
from 79 patients diagnosed with Hirschsprung's disease (HD) (n = 49), CIHG (n =
25), and AIHG (n = 5) collected between January 1996 and December 2015.
Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin
and eosin staining and immunohistochemical staining using Hu C/D and CD56. We
evaluated (immuno)histopathological findings, counted the number of ganglion
cells, and measured the size of Auerbach's plexus. Hu C/D labeled neuronal cell
bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion
cells in Auerbach's plexus in the normoganglionic segment (NGS) were
immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were
replaced by CD56-positive extrinsic nerve fibers and bundles. The number of
ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p
< 0.05). Auerbach's plexus was significantly smaller in CIHG (p < 0.05) but in
AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56
is useful for definitive histopathological diagnosis of IHG.
PMID- 28424866
TI - Histopathological findings of extra-ileal manifestations at initial diagnosis of
Crohn's disease-related ileitis.
PMID- 28424867
TI - J-shaped relationship between habitual coffee consumption and 10-year (2002-2012)
cardiovascular disease incidence: the ATTICA study.
AB - PURPOSE: The purpose of this work was to evaluate the association between coffee
consumption and 10-year cardiovascular disease (CVD) incidence in the ATTICA
study, and whether this is modified by the presence or absence of metabolic
syndrome (MetS) at baseline. METHODS: During 2001-2002, 3042 healthy adults (1514
men and 1528 women) living in the greater area of Athens were voluntarily
recruited to the ATTICA study. In 2011-2012, the 10-year follow-up was performed
in 2583 participants (15% of the participants were lost to follow-up). Coffee
consumption was assessed by a validated food-frequency questionnaire at baseline
(abstention, low, moderate, heavy). Incidence of fatal or non-fatal CVD event was
recorded using WHO-ICD-10 criteria and MetS was defined by the National
Cholesterol Education Program Adult Treatment panel III (revised) criteria.
RESULTS: Overall, after controlling for potential CVD risk factors, the
multivariate analysis revealed a J-shaped association between daily coffee
drinking and the risk for a first CVD event in a 10-year period. Particularly,
the odds ratio for low (<150 ml/day), moderate (150-250 ml/day) and heavy coffee
consumption (>250 ml/day), compared to abstention, were 0.44 (95% CI 0.29-0.68),
0.49 (95% CI 0.27-0.92) and 2.48 (95% CI 1.56-1.93), respectively. This inverse
association was also verified among participants without MetS at baseline, but
not among participants with the MetS. CONCLUSIONS: These data support the
protective effect of drinking moderate quantities of coffee (equivalent to
approximately 1-2 cups daily) against CVD incidents. This protective effect was
only significant for participants without MetS at baseline.
PMID- 28424868
TI - Non-invasive measurements of the dynamic changes in the ciliary muscle,
crystalline lens morphology, and anterior chamber during accommodation with a
high-resolution OCT.
AB - PURPOSE: The purpose of the study was to assess non-invasively the changes in the
anterior chamber eye, crystalline lens morphology, and ciliary muscle during
accommodation by means of an anterior chamber optical coherence tomographer
(OCT), and correlate them with vergence. METHODS: Twenty-five eyes of twenty-five
healthy subjects, whose mean age was 29.9+/-7.1 years, were included and measured
with an anterior chamber OCT. The central corneal thickness (CCT), anterior
chamber depth (ACD), anterior crystalline lens radius of curvature (ALRC),
crystalline lens thickness (CLT), and ciliary muscle area (CMA) were measured for
each participant at 0, -1, -2, and -3 D of target vergence. A linear model was
used to assess the correlation of each eye parameter with the vergence demand.
RESULTS: The mean CCT showed no change for all the accommodative stimuli. The
mean ACD and ALRC decreased with the vergence, about 4.5 and 30 % at -3 D,
respectively. On the contrary, the CLT and CMA showed an opposite tendency, where
the mean CLT was increased by 4.0 % and the mean CMA was done by 26% at -3 D.
Statistical significant differences (p < 0.001) were obtained among all vergences
for each eye metric, except for the CCT (p = 0.76). CONCLUSION: The ACD and ALRC
decreased about 2 and 10 % per dioptre of accommodation, respectively; whereas
the CLT and CMA increased about 2 and 9 %, respectively. These results add
knowledge regarding the understanding of accommodation and give new perspectives
for biomechanics and biometry.
PMID- 28424869
TI - Review on diagnosis and management of urolithiasis in pregnancy: an ESUT
practical guide for urologists.
AB - PURPOSE: Management of urolithiasis in pregnancy can be challenging for most
urologists with diagnostic and treatment dilemma to ensure the best outcome for
both mother and fetus. We wanted to review the literature for urolithiasis in
pregnancy with a practical management guide for urologists. METHODS: A non
systematic review of literature was carried out for all English language
literature using Medline. To ensure a more comprehensive search, the review of
diagnosis and management of pregnant patients with urolithiasis was carried out
separately, by two authors independently. Due to diagnostic complexity,
investigations (US, CT, MRI) carried out were assessed separately. RESULTS: Our
search included diagnostic studies such as US, CT and MRI (73, 20 and 27
articles, respectively) and management studies (55 articles in total). Details on
etiology, radiation risk, safety of various diagnostic modalities, medications
and treatment options are covered through an evidence-based approach. We provide
a practical guide for urologists in what is clearly a stressful situation for
patient and physician alike. CONCLUSIONS: Urolithiasis in pregnancy needs a
careful multidisciplinary management to achieve good outcomes for both mother and
baby. Our review shows that a balanced approach for diagnosis and treatment seems
to achieve the best outcomes in pregnancy.
PMID- 28424870
TI - High intensity interval training does not impair strength gains in response to
resistance training in premenopausal women.
AB - PURPOSE: To compare the increases in upper- and lower-body muscle strength in
premenopausal women performing resistance training (RT) alone or alongside
concurrent high-intensity interval training (CT). METHODS: Sixteen women (26-40
years) were randomly assigned into two groups that performed either RT or CT.
Both groups performed the same RT program; however, CT performed additional high
intensity interval training (HIIT) on a bicycle ergometer before RT. The study
lasted 8 weeks and the participants were tested for ten repetition maximum (10RM)
load in elbow flexion (barbell biceps curl) and knee extension exercises pre- and
post-intervention. RT was performed with 10-12 repetitions to self-determined
repetition maximum in the first four weeks and then progressed to 8-10. During
CT, HIIT was performed before RT with six 1-min bouts at 7-8 of perceived
subjective exertion (RPE) and then progressed to eight bouts at 9-10 RPE.
RESULTS: Analysis of variance revealed significant increases in upper and lower
body strength for both the RT and CT groups. Biceps barbell curl 10RM load
increased from 12.9 +/- 3.2 kg to 14 +/- 1.5 kg in CT (p < 0.05) and from 13 +/-
1.8 kg to 15.9 +/- 2.5 kg in RT (p < 0.05), with no significant between-groups
differences. Knee extension 10RM increase from 31.9 +/- 11.6 kg to 37.5 +/- 8.5
kg for CT (p < 0.05) and from 30.6 +/- 8.6 kg to 41.2 +/- 7.4 kg for RT (p <
0.05). CONCLUSION: In conclusion, performing HIIT on a cycle ergometer before
resistance training does not seem to impair muscle strength increases in the knee
extensors or elbow flexors of pre-menopausal women. This information should be
considered when prescribing exercise sessions, since both activities may be
combined without negative effects in muscle strength.
PMID- 28424872
TI - Percutaneous endoscopic sigmoidopexy using T-fasteners for management of sigmoid
volvulus.
AB - BACKGROUND: Sigmoid volvulus (SV) is the third leading cause of large bowel
obstruction after colonic neoplasms and diverticular disease. SV has
traditionally been managed via endoscopic detorsion and decompression followed by
non-emergent surgical resection owing to the high risk of recurrence. Most cases
of SV occur in elderly debilitated patients with multiple comorbidities and may
not be candidates for surgical resection. Endoscopic sigmoidopexy has been
described as an alternative to surgical resection. Here, we describe our
experience with endoscopic sigmoidopexy using T-fasteners. METHODS: Three
patients with recurrent SV that were identified as poor surgical candidates by
our colorectal surgery team underwent endoscopic sigmoidopexy. The patients
received preoperative bowel preparation. A colonoscope was inserted and the site
of the volvulus was visualized and assessed for adequate decompression.
Subsequently, four points of fixation were identified and T-fasteners were
deployed. RESULTS: Two patients underwent successful sigmoidopexy without any
complications or recurrence on follow-up. One patient developed post procedure
pneumoperitoneum that was successfully treated conservatively; however, he passed
away from their underlying comorbidities. CONCLUSION: Overall, preliminary
results for sigmoidopexy using T-fasteners have been promising, offering a
potential option to prevent recurrence in high risk patients unsuitable for
surgical intervention.
PMID- 28424871
TI - Final analysis of the randomised PEAK trial: overall survival and tumour
responses during first-line treatment with mFOLFOX6 plus either panitumumab or
bevacizumab in patients with metastatic colorectal carcinoma.
AB - PURPOSE: To report planned final overall (OS) and progression-free survival (PFS)
analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with
previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer
(mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary
endpoint was PFS; secondary endpoints included OS, objective response rate,
duration of response (DoR), time to response, resection and safety. Treatment
effect by tumour RAS status was a prespecified objective. Exploratory analyses
included early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: One
hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS
was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months;
hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029)
and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p =
0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab
was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3
versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and
RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR =
0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were
improved in the panitumumab group. More panitumumab patients experienced >=30%
ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No
new safety signals occurred. CONCLUSIONS: First-line panitumumab + mFOLFOX6
increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.
PMID- 28424873
TI - The changes in the reproductive barrier between hexaploid wheat (Triticum
aestivum L.) and rye (Secale cereale L.): different states lead to different
fates.
AB - MAIN CONCLUSION: The changes in the reproductive barrier between hexaploid wheat
( Triticum aestivum L.) and rye ( Secale cereale L.) can be induced using in situ
embryo rescue of abnormal embryos, yielding stable fertile amphidiploid plants.
In intergeneric crosses between hexaploid wheat (Triticum aestivum L.) and rye
(Secale cereale L.), postzygotic barriers may occur at different stages of hybrid
development. One such mechanism is embryo lethality, which is genetically
determined by the interaction and expression of two incompatible genes in wheat
(Eml-A1) and rye (Eml-R1). Using in vitro culture methods as stressors, we
overcame this hybrid lethality. Normal and abnormal embryos were observed to
build embryogenic calli and produce regenerated plantlets in a similar manner.
The high regenerative capacity of the abnormal embryos led us to conclude that
the reproductive barrier in these intergeneric hybrids may have an epigenetic
origin that can be easily overcome by culturing immature embryos via callus
induction. After colchicine treatment during callus culture, amphidiploid plants
were obtained. However, most of these plants did not produce seeds, due mainly to
sterility of the pollen but also of the embryo sacs. These findings demonstrate
that hybrid sterility affects both male and female gametophytes in plants
obtained from abnormal embryos. The key roles of double fertilization and stress
factors in the implementation of the apical meristem formation program in embryos
from incompatible intergeneric crosses between hexaploid wheat and rye during in
vitro culture are discussed. We also propose a hypothetical model for a wheat-rye
lethality system involving differential expression of incompatible wheat Eml-A1
and rye Eml-R1b alleles in an identical genetic background.
PMID- 28424875
TI - Erratum to: Neuropsychological improvement after posterior fossa arachnoid cyst
drainage.
PMID- 28424874
TI - Identification of OsMYC2-regulated senescence-associated genes in rice.
AB - MAIN CONCLUSION: The jasmonic acid (JA)-responsive transcription factor OsMYC2
acts as a positive regulator of leaf senescence by direct regulation of some
senescence-associated genes in rice. OsMYC2, a transcription factor (TF), acts as
a positive regulator of jasmonic acid (JA) signaling involved in development and
defense in rice. Here, we report that OsMYC2 plays an important role in leaf
senescence under dark-induced senescence (DIS) conditions. Overexpression of
OsMYC2 significantly promoted leaf senescence, indicated by reduction of
chlorophyll content under DIS conditions in rice. Leaf senescence under the DIS
conditions was negatively regulated by OsJAZ8, a rice jasmonate ZIM-domain
protein involved in the JA signaling pathway. OsMYC2 upregulated the expression
of some senescence-associated genes (SAGs) and selectively bound to the G-box/G
box-like motifs in the promoters of some SAGs in vivo. These results suggest that
OsMYC2 acts as a positive regulator of leaf senescence by direct- or indirect
regulation of SAGs in rice.
PMID- 28424876
TI - Extent of surgical resection and adjuvant temozolomide improves survival in
pediatric GBM: a single center experience.
AB - BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance
of concurrent and adjuvant temozolomide is not known in this subset of patients.
METHODS: We retrospectively analyzed our database between 2000 and 2015. All
patients were treated with maximally safe surgical resection. This was followed
by a uniform treatment schedule of post-operative radiation with concurrent daily
temozolomide at 75 mg/m2. Radiation dose was 60 Gy in 30 fractions planned by 3
dimensional conformal radiotherapy. Concurrent and adjuvant temozolomide was used
in all patients treated after 2007. Four weeks later, adjuvant temozolomide was
started at 150 mg/m2, day 1 to 5 every 28 days and escalated to 200 mg/m2 from
the second cycle onwards if well tolerated. Log-rank test was used to compare
survival distribution. The data was analyzed using SPSS (version 16). RESULTS:
Fifty-one patients were analyzed. Median age was 14 years (range: 5 to 21 years).
Thirty-five males and 16 females were noted. Median symptom duration was 4
months. Twenty-eight patients underwent a gross total resection (GTR) while 17
underwent a subtotal resection; six patients underwent decompression. Thirty
three patients received concurrent chemotherapy while 27 received adjuvant
chemotherapy. Median progression-free survival (PFS) was 15.1 months. One- and 3
year PFS was 54.4% and 3-year PFS was 24.6.7%. The median overall survival was
17.4 months. In univariate analysis survival was better for gross total resection
(17.4 months vs. 11.5 months; p = 0.037), and significance maintained after
multivariate analysis p = 0.026, HR 3.069, 95% CI 1.14-8.23. In univariate
analysis, survival was better for patients receiving temozolomide but did not
achieve significance. However, in multivariate analysis, use of temozolomide was
associated with significantly improved survival p = 0.036, HR 3.315, 95% CI 1.07
10.19. CONCLUSIONS: GTR improves survival significantly in pGBM. Adjuvant
temozolomide may improve survival in pGBM.
PMID- 28424877
TI - [Fuchs uveitis].
AB - Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation,
which is associated with a gradual onset of decreased visual acuity. The clinical
manifestation of the triad of heterochromia, cataract and glaucoma varies
considerably. This explains the often delayed diagnosis. Although the aetiology
and pathogenesis of the changes are still unclear, there is no doubt that
infections play a significant role. Intraocular antibodies directed against
rubella viruses show a high association with the disease pattern, and their
detection can even be used to support the diagnosis. The treatment of FU is
limited to symptomatic measures. Corticosteroids are usually only moderately
effective and should be used with caution due to adverse effects, with
progression of cataract and secondary glaucoma. The prognosis of the disease can
be regarded as favourable and depends essentially on the secondary changes.
PMID- 28424878
TI - Oral health in patients with renal disease: a longitudinal study from predialysis
to kidney transplantation.
AB - OBJECTIVES: The aim of this longitudinal study was to compare the oral health of
chronic kidney disease patients at the predialysis (baseline) and post
transplantation (follow-up) stages and to investigate differences in oral health
between diabetic nephropathy and other kidney disease patients at follow-up.
MATERIALS AND METHODS: Fifty-three kidney disease patients (34 men) aged 31-86
years were followed up to 157 months. Clinical and radiological oral
examinations, salivary and laboratory analyses, and oral health behavior
questionnaires were conducted at the predialysis and follow-up stages at Helsinki
University Hospital, Finland. Oral inflammatory burden was estimated by
calculating deep periodontal pockets, periodontal inflammatory burden (PIBI),
decayed, missing, and filled teeth (DMFT), and total dental indices (TDI).
Results were analyzed using cross-tabulation Pearson chi-square or Fisher's exact
test and the Mann-Whitney U test, and the McNemar and Wilcoxon signed-rank test.
RESULTS: At the predialysis stage, patients more often had calculus and deep
periodontal pockets; TDI, PIBI, number of teeth, and salivary flow rates were
also statistically significantly higher compared to follow-up. At follow-up,
diabetic nephropathy patients more often had Candida growth, more plaque, and
used more drugs and had lower stimulated salivary flow than patients with other
kidney diseases. CONCLUSION: Oral health was better at follow-up than at the
predialysis stage; however, attention should be given to the lower salivary flow
rate and higher number of drugs used at that stage. CLINICAL RELEVANCE: This
study confirms the importance of treating oral infectious foci at the predialysis
stage in order to prevent adverse outcomes after kidney transplantation.
PMID- 28424879
TI - Drinking Water Management and Governance in Canada: An Innovative Plan-Do-Check
Act (PDCA) Framework for a Safe Drinking Water Supply.
AB - Drinking water management in Canada is complex, with a decentralized, three
tiered governance structure responsible for safe drinking water throughout the
country. The current approach has been described as fragmented, leading to
governance gaps, duplication of efforts, and an absence of accountability and
enforcement. Although there have been no major waterborne disease outbreaks in
Canada since 2001, a lack of performance improvement, especially in small
drinking water systems, is evident. The World Health Organization water safety
plan approach for drinking water management represents an alternative
preventative management framework to the current conventional, reactive drinking
water management strategies. This approach has seen successful implementation
throughout the world and has the potential to address many of the issues with
drinking water management in Canada. This paper presents a review and strengths
weaknesses-opportunities-threats analysis of drinking water management and
governance in Canada at the federal, provincial/territorial, and municipal
levels. Based on this analysis, a modified water safety plan (defined as the plan
do-check-act (PDCA)-WSP framework) is proposed, established from water safety
plan recommendations and the principles of PDCA for continuous performance
improvement. This proposed framework is designed to strengthen current drinking
water management in Canada and is designed to fit within and incorporate the
existing governance structure.
PMID- 28424880
TI - Herbicide Toxicity Testing with Non-Target Boreal Plants: The Sensitivity of
Achillea millefolium L. and Chamerion angustifolium L. to Triclopyr and Imazapyr.
AB - Terrestrial plant toxicity tests were conducted to determine the sensitivity of
two boreal plants, yarrow (Achillea millefolium L.) and fireweed (Chamerion
angustifolium L.), to the herbicides imazapyr and triclopyr. Both plants are
common non-target species on northern powerline rights-of-way where the impacts
of proposed herbicide applications are of concern. In the vegetative vigour test,
triclopyr foliar spray caused extensive damage to A. millefolium at <50% of the
maximum field application rate (inhibition concentration (IC)50 = 1443.8 g a.i.
ha-1) and was lethal to C. angustifolium at the lowest dose tested (1210.9 g a.i.
ha-1). Both species demonstrated extremely high sensitivity to imazapyr foliar
spray: IC50s = 8.29 g a.i. ha-1 and 4.82 g a.i. ha-1 (<1.5% of the maximum field
rate). The seedling emergence and seedling growth tests were conducted in the
organic horizon of five boreal soils. Few differences in herbicide
bioavailability between soils were detected. Triclopyr limited growth of A.
millefolium, C. angustifolium and standard test species Calamagrostis canadensis
at low levels (most IC50 estimates between 2-20 ug g-1). For imazapyr, IC50
estimates could not be calculated as there was >75% inhibition of endpoints at
the lowest doses of ~2 ug g-1. A foliar application of triclopyr or imazapyr for
woody species control would likely cause significant damage to boreal non-target
plants. The high sensitivity of both species to herbicide residues in soil
indicates long term impacts are dependent on herbicide degradation rates in
northern conditions. A. millefolium performed well and is recommended for use in
toxicity testing relevant to boreal regions.
PMID- 28424881
TI - Screening of commercial enzymes for poly(ethylene terephthalate) (PET) hydrolysis
and synergy studies on different substrate sources.
AB - Poly(ethylene terephthalate) (PET) is one of the most consumed plastics in the
world. The development of efficient technologies for its depolymerization for
monomers reuse is highly encouraged, since current recycling rates are still very
low. In this study, 16 commercial lipases and cutinases were evaluated for their
abilities to catalyze the hydrolysis of two PET samples. Humicola insolens
cutinase showed the best performance and was then used in reactions on other PET
sources, solely or in combination with the efficient mono(hydroxyethyl
terephthalate)-converting lipase from Candida antarctica. Synergy degrees of the
final titers of up to 2.2 (i.e., more than double of the concentration when both
enzymes were used, as compared to their use alone) were found, with increased
terephthalic acid formation rates, reaching a maximum of 59,989 umol/L (9.36
g/L). These findings open up new possibilities for the conversion of post
consumer PET packages into their minimal monomers, which can be used as drop in
at existing industrial facilities.
PMID- 28424882
TI - Effectiveness of dry needling and high-volume image-guided injection in the
management of chronic mid-portion Achilles tendinopathy in adult population: a
literature review.
AB - Achilles tendinopathy is a common overuse condition affecting the adult
population. The incidence is on the rise because of greater participation of
people in recreational or competitive sporting activities. There are several
treatment options available both non-operative and operative. Ultrasound-guided
dry needling and high-volume image-guided injection is relatively a new
procedure. The aim of this study was to find out the effectiveness of dry
needling and HVIGI in the management of mid-portion chronic Achilles tendinopathy
by performing a literature review. Search strategy was devised to find the
suitable articles for critical appraisal using the electronic databases. Four
articles were selected for critical appraisal, and these papers showed good short
to long-term results of image-guided high-volume injection in the management of
Achilles tendinopathy. We conclude that high-volume image-guided injection is
effective in the management of Achilles tendinopathy. It provides good short- and
medium-term relief of symptoms. It should be considered as one of the many
options available for this condition.
PMID- 28424883
TI - Acute basophilic leukemia with add(3)(q12) accompanied by histamine excess
symptoms.
PMID- 28424884
TI - Principle and basic property of the sequential flow pump.
AB - In the emergency care field, early treatment of acute heart or respiratory
failure has been a global concern. In severe cases, patients are frequently
required to be on an extracorporeal membrane oxygenator (ECMO) life support. To
make the ECMO system more compact and portable, we proposed a sequential flow
type centrifugal pump named the sequential flow pump (SFP). In this study,
principle and basic properties of this novel blood pump were examined by
computational fluid dynamic (CFD) analysis and an experimental model. In the SFP,
fluid is given centrifugal force sequentially twice with a single closed
impeller. This sequential pressurization mechanism enables high-pressure output
without high impeller speed. To realize easy integration of a blood pump with an
artificial lung, the inlet and outlet ports are located at lateral side and
center of the pump, respectively, which is the reverse configuration of
conventional centrifugal pumps. The computational model was composed for CFD
analysis and the experimental model was developed for the experiment of the
actual pump. For both models, dimension of the impeller and volute was designed
to be equal. In the CFD analysis, the SFP could generate higher performance than
the single pressurization model with the same rotational speed of the impeller.
Basic property of the experimental model was very similar to that of the
computational model. The results showed the possibility that the SFP would be
more suitable for the compact ECMO system than conventional centrifugal pumps.
PMID- 28424885
TI - Bedside repositioning of a dislocated Avalon-cannula in a running veno-venous
ECMO.
AB - We report a repositioning maneuver of a dislocated Avalon Elite dual lumen
catheter during ongoing veno-venous ECMO support. The inferior tip of the
catheter dislocated into a liver vein, which was accompanied by a dramatic
decrease in pump flow. After standard repositioning maneuvers under transthoracic
echocardiographic guidance had failed, a special guiding sheath was inserted into
the main lumen through a Y-connector with a valve. Over this valve, a stiff wire
could be placed into the inferior vena cava to help guiding the catheter back
into the correct position.
PMID- 28424886
TI - Detection of koi herpesvirus (KHV) using a monoclonal antibody against Cyprinus
carpio IgM.
AB - Koi herpesvirus disease (KHVD) is associated with high mortality in both common
carp and koi carp (Cyprinus carpio L.) worldwide. The indirect detection of fish
viruses based on the identification of antibodies has emerged as a practical and
reliable means of diagnosis. Thus, it is important to create monoclonal
antibodies (MAbs) against carp IgM. By using hybridoma-monoclonal antibody
technology, one hybridoma cell line secreting MAbs against IgM from carp was
established. In western blot analysis, the secreted MAb from cell line A5-E10
recognized the heavy chain of IgM from common carp or koi but did not react with
immunoglobulins from three different fish species: grass carp (Ctenopharyngodon
idella), tilapia (Oreochromis mossambicus) and Mandarin fish (Siniperca chuatsi).
These results demonstrated that this MAb is highly specific for the IgM of carp
and suggested that it can be used for monitoring the immunity level of carp, for
example for indirect KHV diagnosis by antibody ELISA. We therefore established an
indirect ELISA, which was tested using 200 serum samples from koi from three
farms. The final results showed that 147 (73.5%) samples were confirmed to be KHV
antibody negative and 53 (26.5%) were definitely positive, containing antibodies
against KHV.
PMID- 28424887
TI - A metagenomics study for the identification of respiratory viruses in mixed
clinical specimens: an application of the iterative mapping approach.
AB - Metagenomic approaches to detect viral genomes and variants in clinical samples
have various challenges, including low viral titers and bacterial and human
genome contamination. To address these limitations, we examined a next-generation
sequencing (NGS) and iterative mapping approach for virus detection in clinical
samples. We analyzed 40 clinical specimens from hospitalized children diagnosed
with acute bronchiolitis, croup, or respiratory tract infections in which virus
identification by viral culture or polymerase chain reaction (PCR) was
unsuccessful. For our NGS data analysis pipeline, clinical samples were pooled
into two NGS groups to reduce sequencing costs, and the depth and coverage of
assembled contigs were effectively increased using an iterative mapping approach.
PCR was individually performed for each specimen according to the NGS-predicted
viral type. We successfully detected previously unidentified respiratory viruses
in 26 of 40 specimens using our proposed NGS pipeline. Two dominant populations
within the detected viruses were human rhinoviruses (HRVs; n = 14) and human
coronavirus NL63 (n = 8), followed by human parainfluenza virus (HPIV), human
parechovirus, influenza A virus, respiratory syncytial virus (RSV), and human
metapneumovirus. This is the first study reporting the complete genome sequences
of HRV-A101, HRV-C3, HPIV-4a, and RSV, as well as an analysis of their genetic
variants, in Taiwan. These results demonstrate that this NGS pipeline allows to
detect viruses which were not identified by routine diagnostic assays, directly
from clinical samples.
PMID- 28424888
TI - Posttraumatic growth and well-being among adolescents and young adults (AYAs)
with cancer: a longitudinal study.
AB - PURPOSE: This study examines posttraumatic growth (PTG) among adolescents and
young adults (AYAs) with cancer, as well as its correlates and trajectories over
time. The study also explores the buffering role of PTG on the associations
between posttraumatic stress (PTS), health-related quality of life (HRQoL), and
psychological distress. METHODS: A multicenter, longitudinal, prospective study
was conducted among AYA cancer patients aged 14-39 years. One hundred sixty-nine
patients completed a self-report measure of PTG (PTGI) and PTS (PDS) 6, 12, and
24 months after baseline (within the first 4 months of diagnosis). At 24-month
follow-up, HRQoL (SF-36) and psychological distress (BSI-18) were also assessed.
RESULTS: Among participants, 14% showed increasing PTG, 45% remained at a stable
high PTG level, 14% showed decreasing PTG, and 27% remained at a stable low PTG
level. AYAs who remained high on PTG were more often younger, female, and
received chemotherapy. PTG level at 6-month follow-up was predictive of mental
HRQoL (beta = 0.19; p = 0.026) and psychological distress (beta = -0.14; p =
0.043) at 24-month follow-up when corrected for PTS and sociodemographic and
clinical covariates. No relationship between PTG and physical HRQoL was found.
The interactive effects of PTS and PTG on outcomes were not significant,
indicating that buffering did not take place. CONCLUSION: This study indicates
that PTG is dynamic and predicts mental well-being outcomes but does not buffer
the effects of PTS. Psychosocial interventions should focus on promoting PTG and
reducing PTS in order to promote the adjustment of AYAs diagnosed with cancer.
PMID- 28424889
TI - Quality of life with biweekly docetaxel and capecitabine in advanced gastro
oesophageal cancer.
AB - PURPOSE: This study aimed to evaluate the feasibility and tolerability of
biweekly docetaxel with capecitabine as first-line treatment in advanced gastro
oesophageal cancer. METHODS: Fifty-three patients at median age of 61 years with
advanced gastric cancer were included in this prospective, non-randomized,
multicentre phase II trial to receive intravenous docetaxel 50 mg/m2 on days 1
and 15, and oral capecitabine 1250 mg/m2 every 12 h, on days 1-7 and 15-21 of
each 28-day cycle. QOL was assessed using EORTC QLQ-C30, together with the
gastric module (QLQ-STO 22). RESULTS: Forty-six patients were evaluable for QOL
analyses. No deterioration in global health status was found. Social functioning
scores improved, and eating difficulties and pain were alleviated during
treatment. The most common grade 3 or 4 toxicity was neutropenia (47%), whereas
neutropenic fever was uncommon (6%). The clinical benefit rate was 60%, including
complete and partial responses as well as stabilized disease. Median overall
survival was 8.8 months (95% CI 5.8-11.9 months), and median time to progression
was 6.2 months (95% CI 4.9-7.5 months). CONCLUSIONS: Biweekly docetaxel with
capecitabine is a feasible treatment in AGC, delivered on an outpatient basis,
with no need for central venous access device. No deterioration of global health
status was reported. In addition, pain and eating difficulties were alleviated
during study treatment. This trial is registered at ClinicalTrials.gov , number
NCT00669370.
PMID- 28424890
TI - Left atrial electromechanical conduction time predicts atrial fibrillation in
patients with mitral stenosis: a 5-year follow-up speckle-tracking
echocardiography study.
AB - Prolonged left atrial electromechanical conduction time is related with atrial
electrical remodeling, and is predictive of the development of atrial
fibrillation. The aim of our study was to examine whether left atrial
electromechanical conduction time (EMT) and left atrial strain as measured by
speckle tracking echocardiography (STE) are predictors for the development of
atrial fibrillation (AF) in patients with mitral stenosis (MS) at 5-year follow
up. A total of 81 patients (61% females; mean age 38.1 +/- 12.1 years) with mild
or moderate MS of rheumatic origin according to ACC/AHA guidelines who were in
sinus rhythm, and were asymptomatic or have NYHA class 1 symptom were included in
the study. AF was searched by 12-lead electrocardiograms or 24-h Holter
recordings during follow-up period. Atrial electromechanical conduction time
(EMT), peak atrial longitudinal strain (PALS) and peak atrial contraction strain
(PACS) were measured by STE. EMTs was defined as the interval between the onset
of P-wave to the peak late diastolic longitudinal strain in the basal lateral and
septal wall. During the follow-up period of 5 years (mean follow-up duration,
48.2 +/- 13.3 months), 30 patients (37%) developed AF on standard 12-lead ECG or
at their 24-h Holter recording. At follow-up, patients who developed AF were
older than patients without AF (42.4 +/- 11.3 vs. 35.6 +/- 11.9, p = 0.014).
Mitral valve area (MVA) (1.39 +/- 0.14 vs. 1.48 +/- 0.18, p = 0.03), PALS (13.4
+/- 4.6 vs. 19 +/- 5.2, p < 0.001) and PACS (6 +/- 2.7 vs. 8.4 +/- 3.8, p =
0.004), were lower in patients who developed AF than in patients who did not
develop. However, EMTs-Septal (208.2 +/- 28.4 vs. 180.2 +/- 38, p = 0.001), and
EMTs-Lateral (247.1 +/- 27.6 vs. 213.3 +/- 43.5, p < 0.001) were longer in
patients with AF than in patients without. In multivariate Cox regression
analysis, PALS and left atrial EMTs-Lateral were independent predictors for
development of AF at follow-up. In patients with mitral stenosis, left atrial
strain and electromechanical conduction time in the lateral wall during the long
term follow-up period are predictive for the development of atrial fibrillation.
Speckle tracking echocardiography is a basic and easily-implemented method based
on left atrial parameters which may be helpful for early detection of atrial
fibrillation in patients with mitral stenosis.
PMID- 28424892
TI - Bayesian characterization of uncertainty in species interaction strengths.
AB - Considerable effort has been devoted to the estimation of species interaction
strengths. This effort has focused primarily on statistical significance testing
and obtaining point estimates of parameters that contribute to interaction
strength magnitudes, leaving the characterization of uncertainty associated with
those estimates unconsidered. We consider a means of characterizing the
uncertainty of a generalist predator's interaction strengths by formulating an
observational method for estimating a predator's prey-specific per capita attack
rates as a Bayesian statistical model. This formulation permits the explicit
incorporation of multiple sources of uncertainty. A key insight is the
informative nature of several so-called non-informative priors that have been
used in modeling the sparse data typical of predator feeding surveys. We
introduce to ecology a new neutral prior and provide evidence for its superior
performance. We use a case study to consider the attack rates in a New Zealand
intertidal whelk predator, and we illustrate not only that Bayesian point
estimates can be made to correspond with those obtained by frequentist
approaches, but also that estimation uncertainty as described by 95% intervals is
more useful and biologically realistic using the Bayesian method. In particular,
unlike in bootstrap confidence intervals, the lower bounds of the Bayesian
posterior intervals for attack rates do not include zero when a predator-prey
interaction is in fact observed. We conclude that the Bayesian framework provides
a straightforward, probabilistic characterization of interaction strength
uncertainty, enabling future considerations of both the deterministic and
stochastic drivers of interaction strength and their impact on food webs.
PMID- 28424891
TI - A phase I dose-escalation study of Selumetinib in combination with Erlotinib or
Temsirolimus in patients with advanced solid tumors.
AB - : Background Combinations of molecularly targeted agents may provide optimal anti
tumor activity and improve clinical outcomes for patients with advanced cancers.
Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective,
allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which
is constitutively activated in many cancers. We investigated the safety,
tolerability, and pharmacokinetics (PK) of selumetinib in combination with
molecularly targeted drugs erlotinib or temsirolimus in patients with advanced
solid tumors. Methods Two-part study: dose escalation, to determine the maximum
tolerated dose (MTD) of selumetinib in combination with erlotinib 100 mg once
daily (QD) or temsirolimus 25 mg once weekly, followed by dose expansion at the
respective combination MTDs to further investigate safety and anti-tumor effects.
Results 48 patients received selumetinib plus erlotinib and 32 patients received
selumetinib plus temsirolimus. The MTD with erlotinib 100 mg QD was selumetinib
100 mg QD, with diarrhea being dose limiting. The most common all grade adverse
events (AEs): diarrhea, rash, nausea, and fatigue. Four (8.3%) patients had >=12
weeks stable disease. The MTD with temsirolimus 25 mg once weekly was selumetinib
50 mg twice daily (BID), with mucositis and neutropenia being dose limiting. The
most commonly reported AEs: nausea, fatigue, diarrhea, and mucositis. Ten (31.3%)
patients had >=12 weeks stable disease. The combination PK profiles were
comparable to previously observed monotherapy profiles. Conclusions MTDs were
established for selumetinib in combination with erlotinib or temsirolimus.
Overlapping toxicities prevented the escalation of selumetinib to its recommended
phase II monotherapy dose of 75 mg BID. TRIAL REGISTRATION: ClinicalTrials.gov
NCT00600496; registered 8 July 2009.
PMID- 28424893
TI - Diversity in growth patterns among strains of the lethal fungal pathogen
Batrachochytrium dendrobatidis across extended thermal optima.
AB - The thermal sensitivities of organisms regulate a wide range of ecological
interactions, including host-parasite dynamics. The effect of temperature on
disease ecology can be remarkably complex in disease systems where the hosts are
ectothermic and where thermal conditions constrain pathogen reproductive rates.
Amphibian chytridiomycosis, caused by the pathogen Batrachochytrium dendrobatidis
(Bd), is a lethal fungal disease that is influenced by temperature. However,
recent temperature studies have produced contradictory findings, suggesting that
our current understanding of thermal effects on Bd may be incomplete. We
investigated how temperature affects three different Bd strains to evaluate
diversity in thermal responses. We quantified growth across the entire thermal
range of Bd, and beyond the known thermal limits (T max and T min). Our results
show that all Bd strains remained viable and grew following 24 h freeze (-12
degrees C) and heat shock (28 degrees C) treatments. Additionally, we found that
two Bd strains had higher logistic growth rates (r) and carrying capacities (K)
at the upper and lower extremities of the temperature range, and especially in
low temperature conditions (2-3 degrees C). In contrast, a third strain
exhibited relatively lower growth rates and carrying capacities at these same
thermal extremes. Overall, our results suggest that there is considerable
variation among Bd strains in thermal tolerance, and they establish a new thermal
sensitivity profile for Bd. More generally, our findings point toward important
questions concerning the mechanisms that dictate fungal thermal tolerances and
temperature-dependent pathogenesis in other fungal disease systems.
PMID- 28424894
TI - The integrity of the nucleus of the lateral olfactory tract is essential for the
normal functioning of the olfactory system.
AB - The nucleus of the lateral olfactory tract (nLOT) is a relatively small component
of the cortical pallial amygdala, with peculiar neurogenic, neurochemical and
connectivity patterns. Although it has been suggested that it might be involved
in non-pheromonal olfactory-guided behaviors, particularly feeding, the
functional implications of the nLOT have never been investigated. In view of this
fact, we have tackled this subject by performing a series of behavioral tests and
by quantifying biological and biochemical parameters in sexually naive adult male
rats that were submitted to bilateral excitotoxic lesions of the nLOT. nLOT
lesioned rats had severe olfactory deficits with inability to detect and
discriminate between odors. Additionally, they did not display innate behavioral
responses to biologically relevant chemosignals. Specifically, nLOT-lesioned rats
did not show avoidance towards predator odors or aggressive behaviors towards
intruders, and had severely impaired sexual behavior. In fact, nLOT lesions
abolished preference for odors of receptive females, reduced chemoinvestigatory
behavior and eliminated mounting behavior. nLOT-lesioned rats had normal
circulating levels of testosterone, did not display anxiety- or depressive-like
behaviors, and had unimpaired cognitive functions and fear acquisition and
memory. Altogether, our results suggest that the nLOT integrity is required for
the normal functioning of the olfactory system.
PMID- 28424895
TI - Risk and protective factors for structural brain ageing in the eighth decade of
life.
AB - Individuals differ markedly in brain structure, and in how this structure
degenerates during ageing. In a large sample of human participants (baseline n =
731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the
magnitude of mean change and variability in changes in MRI measures of brain
macrostructure (grey matter, white matter, and white matter hyperintensity
volumes) and microstructure (fractional anisotropy and mean diffusivity from
diffusion tensor MRI). All indices showed significant average change with age,
with considerable heterogeneity in those changes. We then tested eleven
socioeconomic, physical, health, cognitive, allostatic (inflammatory and
metabolic), and genetic variables for their value in predicting these differences
in changes. Many of these variables were significantly correlated with baseline
brain structure, but few could account for significant portions of the
heterogeneity in subsequent brain change. Physical fitness was an exception,
being correlated both with brain level and changes. The results suggest that only
a subset of correlates of brain structure are also predictive of differences in
brain ageing.
PMID- 28424896
TI - Maximum Tongue Pressure is Associated with Swallowing Dysfunction in ALS
Patients.
AB - Maximum tongue pressure (MTP) measurement is a convenient, less invasive
assessment that has been developed to quantify tongue strength; however, it is
unclear whether MTP is useful for the detection of swallowing disorders in
amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to
clarify the relationship between MTP and the characteristics of swallowing
disorders on videofluorography and to determine the usefulness of tongue pressure
measurement for the assessment of swallowing function in ALS patients. Twenty
five ALS patients were evaluated according to the ALS functional rating scale
revised (ALSFRS-R), and their ability to swallow yogurt was observed via
videofluorography. MTP was measured using a device (TPM-01, JMS, Hiroshima)
equipped with a balloon probe. Then, the relationships between the ALSFRS-R
score, swallowing function, and MTP were analyzed. MTP was significantly lower in
the subjects with reduced tongue function (p = 0.002) or with pharyngeal residue
(p = 0.006) than in the subjects with normal characteristics. Bolus formation and
oral transit time and pharyngeal transit time were significantly prolonged among
those with reduced MTP. MTP at a cut-off value of 21.0 kPa was associated with a
full score on the bulbar-related items of the ALSFRS-R. MTP may serve as a new
diagnostic tool for the early detection of swallowing dysfunction in ALS
patients, because of its good relationship with their swallowing characteristics.
PMID- 28424897
TI - First Step in Telehealth Assessment: A Randomized Controlled Trial to Investigate
the Effectiveness of an Electronic Case History Form for Dysphagia.
AB - The need for developing effective telehealth tools for dysphagia management is
high not only for people who live in rural areas, but also for individuals with
mobility/access limitations. We aimed to develop an electronic case History
Tool/form (thereafter, e-HiT) for dysphagia, and compare its effectiveness with
its paper-based version (PBV) on completion time, completeness, independence, and
patient perceptions/satisfaction. Secondarily, we examined associations between
the aforementioned variables and predictor variables, such as age, cognition, and
computer/internet use. Forty adults who expressed concerns with eating/swallowing
participated. To compare both versions, a randomized, controlled two-period
crossover design was used. In Visit 1, Group A completed the e-HiT and Group B
completed the PBV. In Visit 2, Group A completed the PBV and Group B completed
the e-HiT. A satisfaction survey was completed post visits. There were no
statistically significant differences for completion time (p = 0.743),
completeness (p = 0.486), and independence (p = 0.738). Patient
perception/satisfaction was significantly higher with the e-HiT (p = 0.004). In
addition, a significant association was found between completion time and age (p
= 0.0063). Our results indicate that completing the e-HiT is as time efficient as
completing the PBV and that both forms elicit the same amount of information with
no or minimal support. Also, completion of the e-HiT yielded significantly higher
satisfaction responses. This is the first study documenting the effectiveness of
the e-HiT for outpatients with dysphagia, providing evidence that the first step
of a swallowing assessment-case history completion-can be effectively completed
via telehealth by individuals with reliable internet connection and basic
computer literacy skills.
PMID- 28424898
TI - Patient Experiences of Swallowing Exercises After Head and Neck Cancer: A
Qualitative Study Examining Barriers and Facilitators Using Behaviour Change
Theory.
AB - Poor patient adherence to swallowing exercises is commonly reported in the
dysphagia literature on patients treated for head and neck cancer. Establishing
the effectiveness of exercise interventions for this population may be undermined
by patient non-adherence. The purpose of this study was to explore the barriers
and facilitators to exercise adherence from a patient perspective, and to
determine the best strategies to reduce the barriers and enhance the
facilitators. In-depth interviews were conducted on thirteen patients. We used a
behaviour change framework and model [Theoretical domains framework and COM-B
(Capability-opportunity-motivation-behaviour) model] to inform our interview
schedule and structure our results, using a content analysis approach. The most
frequent barrier identified was psychological capability. This was highlighted by
patient reports of not clearly understanding reasons for the exercises,
forgetting to do the exercises and not having a system to keep track. Other
barriers included feeling overwhelmed by information at a difficult time (lack of
automatic motivation) and pain and fatigue (lack of physical capability). Main
facilitators included having social support from family and friends, the desire
to prevent negative consequences such as long-term tube feeding (reflective
motivation), having the skills to do the exercises (physical capability), having
a routine or trigger and receiving feedback on the outcome of doing exercises
(automatic motivation). Linking these findings back to the theoretical model
allows for a more systematic selection of theory-based strategies that may
enhance the design of future swallowing exercise interventions for patients with
head and neck cancer.
PMID- 28424899
TI - A polysomnographic study in parkinsonian patients treated with intestinal
levodopa infusion.
AB - Sleep disorders are very common in advanced Parkinson's disease (PD) and have a
significant negative impact on the quality of life of patients. Questionnaire
based studies suggest that sleep quality might improve following levodopa
carbidopa intestinal gel (LCIG) infusion. The objective of this study was to
evaluate the impact of LCIG infusion and subsequent oral medication changes on
polysomnography (PSG) and sleep symptoms in advanced PD patients. Eleven PD
patients underwent PSG at baseline and after 3.8 +/- 1.2 months of LCIG
treatment. LCIG infusion therapy was halted during PSG. Patients were assessed
with the Unified-PD-rating-Scale and completed the PD-Sleep-Scale-version-2 (PDSS
2), the Epworth Sleepiness Scale and the RBD single question. Subjective sleep
quality improved in all patients. PSG showed a reduction of the number of
awakenings in sleep, a trend towards a lower apnea-hypopnea index and no change
in sleep latency, total sleep time and sleep efficiency. There was a positive
correlation between the number of awakenings and PDSS-2 scores for "difficulty
staying asleep", "muscle cramps of arms or legs" and "urge to move arms or legs".
Motor complications and activities of daily living improved with LCIG. Subjective
sleep quality improved significantly and the PSG study showed a less fragmented
sleep pattern in advanced PD patients treated with LCIG infusion.
PMID- 28424900
TI - Seasonal variation in multiple sclerosis relapse.
AB - Relapses are a characteristic clinical feature of multiple sclerosis (MS), but an
appreciation of factors that cause them remains elusive. In this study, we have
examined seasonal variation of relapse in a large population-based MS cohort and
correlated observed patterns with age, sex, disease course, and climatic factors.
Relapse data were recorded prospectively in 2076 patients between 2005 and 2014.
3902 events were recorded in 1158 patients (range 0-24). There was significant
seasonal variation in relapse rates (p < 0.0001) and this was associated with
monthly hours of sunshine (odds ratio OR 1.08, p = 0.02). Relapse rates were
highest in patients under the age of 30 (OR 1.42, p = 0.0005) and decreased with
age. There was no evidence of different relapse rates for males compared to
females (OR 0.90, p = 0.19). Identification of potentially modifiable
environmental factors associated with temporal variation in relapse rates may
allow alteration of risk on a population basis and alteration of outcome of
established disease once established. Future epidemiological studies should
examine dynamic environmental factors with serial prospective measurements and
biological sampling. Significant seasonal differences in relapse rates highlight
the importance of environmental factors in disease expression and should be taken
into account when planning clinical trials in which relapse frequency is an
outcome. In addition, identification of potentially modifiable factors associated
with this variation may offer unique opportunities for alteration of risk of
relapse and long-term outcome on a population level, and suggest putative
biological mechanisms for relapse initiation.
PMID- 28424901
TI - Driving with a neurodegenerative disorder: an overview of the current literature.
AB - Driving is important for employment, social activities, and for the feeling of
independence. The decision to cease driving affects the quality of life and has
been associated with reduced mobility, social isolation, and sadness. Patients
with neurodegenerative disorders can experience difficulties while driving due to
their cognitive, motor, and behavioral impairments. The aim of this review is to
summarize the available literature on changes in driving competence and behavior
in patients with neurodegenerative disorders, with a particular focus on
Huntington's (HD), Parkinson's (PD), and Alzheimer's disease (AD). A systematic
literature search was conducted in the PubMed/Medline database. Studies using on
road or simulated driving assessments were examined in this review. In addition,
studies investigating the association between cognitive functioning and driving
were included. The review identified 70 studies. Only a few publications were
available on HD (n = 7) compared to PD (n = 32) and AD (n = 31). This review
revealed that driving is impaired in patients with neurodegenerative disorders on
all levels of driving competence. The errors most commonly committed were on the
tactical level including lane maintenance and lane changing. Deficits in
executive functioning, attention, and visuospatial abilities can partially
predict driving competence, and the performance on neuropsychological tests might
be useful when discussing potential driving cessation. Currently, there is no
gold standard to assess driving ability using clinical measures such as
neuropsychological assessments, so more studies are necessary to detect valid
screening tools and develop useful and reliable evidence-based guidelines.
PMID- 28424902
TI - Physical and psychosocial aspects of adolescent and young adults after allogeneic
hematopoietic stem-cell transplantation: results from a prospective multicenter
trial.
AB - PURPOSE: Allogeneic hematopoietic stem-cell transplantation (alloHSCT) is
physically and psychosocially demanding. Among transplant recipients, adolescent
and young adults (AYA) represent a special group, as disease occurs early in
life, resulting in the prospect of long survival time and high burden of alloHSCT
sequelae. However, data focusing on AYA undergoing alloHSCT are rare. METHODS:
Data resulting from a prospective multicenter trial initially focusing on graft
versus-host disease (GvHD) after alloHSCT were reused to analyse the differences
between AYA and elderly patients. In total, data of 205 alloHSCT recipients were
evaluated. Patients completed the FACT-BMT, HAP, SF-36, 24-AM, LOT-R, BSSS, HADS,
and GvHD questionnaires. RESULTS: Median age of AYA and non-AYA patients was 29
and 52 years. Using 24-AM-Test, evaluating personality traits, non-AYA reported
to be more conscientious (p = 0.033). However, AYA described higher quality of
life regarding physical role functioning (p = 0.001), physical functioning (p =
0.002), bodily pain (p = 0.023), and emotional role function (p = 0.027) in the
SF-36. General health perception, vitality, social role functioning, and mental
health were comparable among both groups. On HAP scale, AYA reported higher
maximum (p = 0.003) and adjusted activity scores (p = 0.002), but showed similar
restrictions regarding activity, self-supply, and self-determination. CONCLUSION:
AYA represent a particular group characterized by higher physical well-being and
activity scores, and significantly vary from non-AYA patients in psychosocial
aspects. Studies covering distinctive features of AYA undergoing alloHSCT are
warranted to improve awareness of the special needs of this group.
PMID- 28424903
TI - ZCCHC12, a novel oncogene in papillary thyroid cancer.
AB - PURPOSE: Thyroid cancer is the most common endocrine malignancy worldwide. The
molecular mechanisms underlying thyroid tumorigenesis remain unclear. Some
studies suggested that the ZCCHC12 gene correlates with certain diseases.
However, the function of ZCCHC12 in thyroid cancer has yet to be determined. This
study investigated the role of the ZCCHC12 gene in papillary thyroid cancer
(PTC). METHODS: We conducted a comprehensive analysis of massively parallel whole
transcriptome resequencing of matched PTC tumors and normal tissues in 19
patients. Results showed that the expression of ZCCHC12 was significantly
upregulated in thyroid cancer. qRT-PCR was performed to confirm previous results.
The functions of the ZCCHC12 gene in PTC cell lines (TPC1 and BCPAP) transfected
with small interfering RNA were determined through cell colony formation assay,
migration assay, and invasion assay. RESULTS: The ZCCHC12 gene was remarkably
upregulated in primary PTC tumors in both validated cohort (T:N = 1.80 +/-
2.58:0.23 +/- 0.50, P < 0.01) and TCGA cohort (T:N = 7.63 +/- 3.25:1.55 +/- 1.71,
P < 0.01). We also achieved area under the curve (AUC of ROC) of 87.9% for the
validated cohort while 91.4% for the TCGA cohort to classify PTC tumors and
normal tissues. ZCCHC12 overexpression correlated with lymph node metastasis in
both cohorts (P < 0.05). In in vitro experiments, ZCCHC12 downregulation
significantly inhibited the colony formation, migration, and invasion of PTC
cells. CONCLUSION: Our study indicated that ZCCHC12 gene has important biological
functions and acts as a metastasis-related oncogene in PTC.
PMID- 28424904
TI - Nanoindentation response of cortical bone: dependency of subsurface voids.
AB - Nanoindentation test results in the axial direction of mouse femurs were the
basis for the current study. Although the majority of the nanoindentation curves
showed a reasonable consistency, some curves showed a significantly softer
response. Detailed investigation, using focused ion beam-scanning electron
microscopy, provided that the softer response is due to subsurface cavities such
as lacunae. Finite element models were developed to simulate the nanoindentation
of mice femur cortical bone samples with and without the incorporation of a
single lacuna underneath the bone surface. Based on the material parameters
determined for the cavity-free tissue, numerical simulations were run for
different cases of cavity size, shape, and location. Spherical cavities with
different size were considered at different distances from the surface. The
results showed that subsurface cavities can lead to 50% higher indentation
compared to an indentation in cavity-free material. Continuing with ellipsoidal
cavities with the center located on the load axis, the results showed a nonlinear
dependency of ellipsoid shape. Hence, the shape of the cavity is important for
the nanoindentation response. The influence of horizontal and vertical offsets of
spherical cavities was studied, thereby the results showed that an increasing
horizontal offset caused a decreasing influence of the vertical distance from the
surface. In perspective, the present study provides information that may help to
get deeper knowledge of nanoindentation load-displacement mechanism taking place
in samples with subsurface cavities.
PMID- 28424905
TI - Association of STAT4 rs7574865 and PTPN22 rs2476601 polymorphisms with rheumatoid
arthritis and non-systemically reacting antibodies in Egyptian patients.
AB - The aim of this study was to investigate association of protein tyrosine
phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and
activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid
arthritis (RA) susceptibility and to assess potential association with the status
of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)
antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and
neopterin were assayed in serum of 100 unrelated RA patients and 114 controls.
STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the
TaqMan allelic discrimination method. The frequency of STAT4 variant allele was
significantly higher in RA patients than in controls (p = 0.01), while the
variant allele of PTPN22 was identified in only two RA patients, in a
heterozygous form and in none of control subjects. The frequency of STAT4 variant
allele carrier genotypes (GT+TT) was significantly higher among RA patients than
in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and
dominant models. The frequency of RF and anti-CCP positivity was significantly
higher among RA patients carrying T allele genotypes compared to patients
carrying wild genotype (P = 0.02 and 0.04, respectively). No significant
associations between STAT4 variant and serum neopterin or disease activity
parameters were identified. Our study confirmed the association of STAT4
rs7574865 polymorphism with RA and was the first to indicate an association with
RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role
in susceptibility to RA in Egyptian patients.
PMID- 28424906
TI - Prevalence and features of metabolic syndrome in childhood-onset systemic lupus
erythematosus.
AB - To estimate the prevalence and features of metabolic syndrome (MetS) in childhood
onset systemic lupus erythematosus (cSLE), we performed a cross-sectional study
of 76 consecutive cSLE patients and 54 healthy controls, age and sex matched. All
individuals were assessed for anthropometric and MetS features according to World
Health Organization (WHO), NCEP Adult Treatment Panel III (NCEP-ATP III), and
International Diabetes Federation (IDF) criteria. The cSLE patients were further
assessed for clinical and laboratory manifestations, disease activity (Systemic
Lupus Erythematosus Disease Activity Index), cumulative damage (Systemic Lupus
International Collaborating Clinics (SLICC)), and current and cumulative drug
exposures. Sixty-nine (90.8%) patients were female with mean age of 16.8 years
[standard deviation (SD) +/-4.0 years]. Mean disease duration was 4.8 years (SD
+/- 4.1). Based on the WHO MetS criteria, MetS was observed in two (2.6%) cSLE
patients. We observed high prevalence of the MetS in cSLE patients according to
NCEP-ATP III MetS criteria (18.4%) (p = 0.002) and according to IDF MetS criteria
(17.1%) (p = 0.003). We did not observe MetS in the control group. No difference
in cSLE patients <18 and >=18 years was observed. We observed an association
between the presence of MetS and SLICC scores in cSLE <18 years and cumulative
corticosteroid dose adjusted by weight in cSLE >=18 years. This study showed that
MetS is frequently observed in cSLE using NCEP-ATP III MetS criteria and IDF MetS
criteria. The identification of MetS is important to indicate cardiovascular
morbidity and mortality in cSLE.
PMID- 28424907
TI - The added value of synovial fluid centrifugation for monosodium urate and calcium
pyrophosphate crystal detection.
AB - The aim of the study was to assess the added value of synovial fluid (SF)
centrifugation for microscopic monosodium urate (MSU) and calcium pyrophosphate
(CPP) crystal detection in patients with arthritis. This is a prospective
observational study using SF samples from joints of patients undergoing joint
arthrocentesis. Two blinded observers assessed the SF smears by polarized light
microscopy for the presence of crystals before as well as after centrifugation.
SF samples were collected from 98 patients with arthritis. After exclusion, 87
samples were eligible for inclusion. Of each sample, 2 smears before and after
centrifugation were prepared and microscopically examined, resulting in 348
smears per observer. Observer 1 identified MSU crystals in 18.4% and CPP in 9.2%
of the smears before as well as after centrifugation. No extra MSU crystal
positive smears were identified after centrifugation. However, centrifugation
yielded 4 additional CPP crystal-positive smears. Observer 2 identified MSU
crystals in 15.5% and CPP crystals in 6.3% of the smears before as well as after
centrifugation. Centrifugation yielded 2 additional MSU crystal-positive smears
and 4 CPP crystal-positive smears. Monosodium urate crystals were well recognized
without centrifugation. Centrifugation of SF had limited additional value for
increasing the amount of MSU-positive smears. However, CPP crystals were
identified in a higher number of smears after centrifugation than before.
Therefore, centrifugation may be of additional value in selected patients with
suspected calcium pyrophosphate deposition disease and to a lesser extent for
gout.
PMID- 28424908
TI - Delayed closure of open abdomen in septic patients treated with negative pressure
wound therapy and dynamic fascial suture: the long-term follow-up study.
AB - INTRODUCTION: Negative pressure wound therapy (NPWT) is widely used in the
treatment of open abdomen (OA). The use of dynamic fascial sutures (DFS)
increases the rate of successful delayed closure by reducing fascial
lateralization. We recently published a prospective controlled trial including 87
patients undergoing abdominal surgery for secondary peritonitis between 2007 and
2012. Patients were treated with NPWT and DFS for approximation of fascial edges.
The present study represents a follow-up assessment of these patients 5-9 years
after OA treatment with NPWT and DFS. METHODS: The 39 patients still alive were
included in the recent study according to the protocol of our last study in 2013.
All patients received a questionnaire regarding long-term complications after OA
treatment between 2007 and 2012. Mean follow-up was 5-9 years. Analyzed
parameters included pain, the presence of incisional hernia, and subsequent
surgical interventions. Results were analyzed quantitatively. RESULTS: One
patient had deceased since the last publication in 2013, and hence 38 patients
were included in the current study. The median age was 60.9 (25.2-86.1) years,
and 17 (44.7%) were females. Overall 56.3% of the original 87 patients had died
during the long-term follow-up period. 21 patients (55.3%) answered the
questionnaire. Six (28.6%) declared that they suffered from pain in the previous
operating field, five (23.8%) at rest, and three (14.3%) during exercise. In five
patients (23.8%), pain lasted for more than 3 months. One patient (4.8%) still
requires analgesic treatment. Among the 21 patients, seven (33.3%) were found to
have incisional hernias. Three hernias (42.9%) were treated by surgery.
CONCLUSION: Incisional hernia rates after OA treatment remain high, but are
accompanied by little pain. The ideal technique of fascial closure after NPWT
should be investigated in further research.
PMID- 28424909
TI - Comparison of clinical outcomes and quality of life between laparoscopic and open
central pancreatectomy with pancreaticojejunostomy.
AB - BACKGROUND: The studies comparing laparoscopic and open central pancreatectomy
with pancreaticojejunostomy are limited. This study aimed to compare clinical
outcomes and quality of life of patients undergoing laparoscopic and open central
pancreatectomy with pancreaticojejunostomy. METHODS: Between December 1997 and
December 2015, patients who underwent central pancreatectomy with
pancreaticojejunostomy were reviewed. Patients were divided into 2 groups as
laparoscopic central pancreatectomy (LCP) and open central pancreatectomy (OCP).
Data considered for comparison analysis were patient demographics, intraoperative
variables, morbidity, postoperative hospital stay, mortality, pathologic
findings, and quality of life (SF-36 questionnaire). RESULTS: Thirty-six patients
(17 LCP and 19 OCP) were included in the final analysis. Baseline characteristics
were similar in the 2 groups. The operating time (280.4 +/- 33.6 vs. 290.5 +/-
62.5 min, p = 0.455) were similar between two groups. LCP group showed
significantly lower estimated blood loss (76.4 +/- 70.3 vs. 390.3 +/- 279.0 ml, p
= 0.001), shorter first flatus time (2.4 +/- 0.9 vs. 3.9 +/- 1.3 days, p =
0.001), and shorter diet start time (4.1 +/- 2.2 vs. 6.1 +/- 2.4 days, p =
0.030). However, the postoperative hospital stay was not significantly different
between two groups (15.6 +/- 12.1 vs. 24.0 +/- 27.5 days, p = 0.347).
Postoperative outcomes, including morbidity (58.8 vs. 52.6%, p = 0.749),
pancreatic fistula rates (>=grade B: 17.6 vs. 36.8%, p = 0.106), and mortality,
were similar in the 2 groups. The median follow-up period was 45 months (range 4
216 months). No local recurrence or distant metastasis was detected in either
group. On the follow-up survey, the total quality of life score (702.9 +/- 47.9
vs. 671.8 +/- 94.1), physical health score (353.9 +/- 24.8 vs. 326.6 +/- 67.6)
and mental health score (349.0 +/- 26.5 vs. 345.2 +/- 34.6) were higher in the
LCP group compared with the OCP group. However, these differences were not
statistically significant (p > 0.05). The score in role physical (100 vs. 73.1 +/
4.8, p = 0.042) was significantly higher in LCP group, and not statistically
significant in other areas (p > 0.05). CONCLUSIONS: LCP with
pancreaticojejunostomy is safe and feasible for benign or borderline malignant
lesions in the pancreatic neck and proximal body. Compared to OCP, LCP is
associated with lower estimated blood loss, faster recovery, and better quality
of life.
PMID- 28424910
TI - Erratum to: Laparoscopic image-based navigation for microwave ablation of liver
tumors: A multi-center study.
PMID- 28424911
TI - Long-term outcomes of endoscopic resection of gastric GISTs.
AB - OBJECTIVE: Although the endoscopic treatment of gastric stromal tumors is a
recently accepted therapy, the long-term outcomes of this approach remain
unknown. The aims of this study were to assess the long-term effectiveness and
safety of endoscopic resection for gastric GISTs. METHODS: A total of 60
consecutive patients undergoing endoscopic resection of gastric GISTs were
enrolled in a retrospective single-center study. Clinical data, perioperative
complications, histopathologic characteristics of the tumors, and long-term
outcomes were recorded. RESULTS: Sixty patients successfully underwent complete
resection of lesions, including 25 cases of endoscopic submucosal dissection
(ESD) and 35 cases of endoscopic full-thickness resection (EFTR), with an average
tumor size of 1.76 +/- 1.55 cm (range 0.5-7.6 cm). The average operation time was
43.97 +/- 26.95 min (range 11.7-138.9 min). Two cases were observed with an
intraoperative hemorrhage of 200 mL, which were successfully managed by
hemostatic forceps. Perforations of 2-11 mm of ESD occurred in four cases (4/25)
and were well closed with endoclips, with no conversions to surgical operation.
Mucosal laceration of esophagus occurred in 1 case, when a large tumor was
removed. The average length of hospitalization was 6.50 +/- 3.06 days (range 3-21
days). Out of a total of 60 patients, 44 (73.3%) were at very low risk, 10
(16.7%) were at low risk, 5 (8.3%) were at intermediate risk, and 1 (1.7%) was at
high risk. All patients were followed-up for 36.15 +/- 12.92 months (range 14-73
months). Primary tumor recurrence occurred in 1 patient who underwent a second
operation after 32 months, and no other cases were observed to have either tumor
recurrence or metastasis. CONCLUSIONS: For long-term outcomes, endoscopic
resection of ESD or EFTR is a safe and effective approach for removing gastric
stromal tumors (<5 cm), and it can be a resection technique for them with no
metastasis.
PMID- 28424912
TI - Rescue EUS-guided intrahepatic biliary drainage for malignant hilar biliary
stricture after failed transpapillary re-intervention.
AB - BACKGROUND: Treatment of unresectable malignant hilar biliary stricture (UMHBS)
is challenging, especially after failure of repeated transpapillary endoscopic
stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS
IBD) is a recent technique for intrahepatic biliary decompression, but
indications for its use for complex hilar strictures have not been well studied.
The aim of this study was to assess the feasibility and safety of EUS-IBD for
UMHBS after failed transpapillary re-intervention. METHODS: Retrospective
analysis of all consecutive patients with UMHBS of Bismuth II grade or higher
who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated
transpapillary interventions. The technical success, clinical success, and
complication rates were evaluated. Factors associated with clinical
ineffectiveness of EUS-IBD were explored. RESULTS: A total of 30 patients (19
women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the
study period. Hilar biliary stricture morphology was classified as Bismuth II,
III, or IV in 5, 13, and 12 patients, respectively. The median number of
preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required
because the following procedures failed: duodenal scope insertion (n = 4),
accessing the papilla after duodenal stent insertion (n = 5), or achieving
desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD
was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22
of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was
managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no
procedure-related mortality. On multivariable analysis, Bismuth IV stricture
predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P =
0.035). CONCLUSIONS: EUS-IBD may be a feasible and effective rescue alternative
with few major complications after failed transpapillary endoscopic re
intervention in patients with UMHBS, particularly for Bismuth II or III
strictures.
PMID- 28424913
TI - Can further gastrectomy be avoided in patients with incomplete endoscopic
resection?
AB - BACKGROUND: Endoscopic resection (ER) is a widely accepted treatment for patients
with early gastric cancer (EGC) with no lymph node metastasis. Occasionally,
however, additional surgery is needed due to an incomplete resection. The purpose
of this study was to detect clinical factors which might identify patients at
greater risk of additional surgery after ER and to suggest an alternative
treatment strategy for these patients. METHODS: This study retrospectively
analyzed 350 patients with gastric cancer who underwent radical gastrectomy and
lymphadenectomy after ER in a single institution between July 2004 and July 2014.
Risk factors for incomplete resection were identified using binary logistic
multiple regression tests and a classification and regression tree analysis.
RESULTS: Residual cancer cells were found in the remnant stomach or lymph node in
96 patients (27.4%). In multivariate analysis, lymphovascular invasion (p <
0.001, odds ratio [OR] 5.619) and depth of invasion greater than the second
submucosal layer (SM2) (p < 0.01, OR 3.224) were independent risk factors for
lymph node metastasis. Positive resection margin (p < 0.001, OR 7.565), depth of
invasion to mucosa (M) and the first submucosal layer (SM1) (p < 0.001, OR
4.219), and size over 3 cm (p < 0.029, OR 2.306) were significant risk factors
for residual tumor in the remnant stomach. Of 106 patients who had invasion of
the M or SM1 without lymphatic invasion at the time of ER, residual cancer was
found in 53 patients. Of these 53 patients, 50 (94.3%) had residual cancer in the
mucosal layer and only one had lymph node metastasis. CONCLUSION: In patients
with EGC with M or SM1 invasion without lymphovascular invasion at the time of
ER, who had an incomplete resection, additional endoscopic treatment or close
monitoring can be performed instead of additional surgery, especially in patients
who are unable to tolerate gastrectomy, for example elderly patients or those
with comorbidities.
PMID- 28424914
TI - Association of femoral head and acetabular fractures on computerized tomography:
correlation with the Judet-Letournel classification.
AB - PURPOSE: Tha aims of this study were to identify the incidence of femoral head
fractures in the setting of acetabular fractures and to determine the
relationship between acetabular fracture pattern, the degree of acetabular
fracture displacement, and the incidence of femoral head fractures. MATERIALS AND
METHODS: This is a retrospective cross-sectional study of 274 patients with 300
acetabular fractures diagnosed on pelvic CT. Acetabular fractures were
categorized using the Judet-Letournel classification system. RESULTS: Femoral
head fractures were present in 18.0% of acetabular fractures. Fracture patterns
with a posterior wall component had a very high (56.3%) incidence of femoral head
fracture. Anterior column and anterior column with posterior hemitransverse
fractures have a very low (3.4%) incidence of femoral head fracture. Anterior hip
dislocation had a 66.7% incidence of femoral head fracture, while posterior
dislocation had a 71.9% incidence. Acetabular fractures displaced by more than 5
mm had a 26.9% incidence of femoral head fracture, while acetabular fracture
displaced less than 5 mm had only 4.2% incidence of femoral head fracture.
CONCLUSION: Femoral head fractures are a very common associated finding in
patients presenting with acetabular fractures. In patients with a posterior wall
component of the fracture or associated hip dislocation, a femoral head fracture
is more likely than not present. Conversely, in acetabular fractures with less
than 5 mm displacement or anterior column fractures without posterior acetabular
involvement, femoral head fractures are very unlikely in the absence of a
dislocation event.
PMID- 28424915
TI - Optimal eye movement strategies: a comparison of neurosurgeons gaze patterns when
using a surgical microscope.
AB - BACKGROUND: Previous studies have consistently demonstrated gaze behaviour
differences related to expertise during various surgical procedures. In micro
neurosurgery, however, there is a lack of evidence of empirically demonstrated
individual differences associated with visual attention. It is unknown exactly
how neurosurgeons see a stereoscopic magnified view in the context of micro
neurosurgery and what this implies for medical training. METHOD: We report on an
investigation of the eye movement patterns in micro-neurosurgery using a state-of
the-art eye tracker. We studied the eye movements of nine neurosurgeons while
performing cutting and suturing tasks under a surgical microscope. Eye-movement
characteristics, such as fixation (focus level) and saccade (visual search
pattern), were analysed. RESULTS: The results show a strong relationship between
the level of microsurgical skill and the gaze pattern, whereas more expertise is
associated with greater eye control, stability, and focusing in eye behaviour.
For example, in the cutting task, well-trained surgeons increased their fixation
durations on the operating field twice as much as the novices (expert, 848 ms;
novice, 402 ms). CONCLUSIONS: Maintaining steady visual attention on the target
(fixation), as well as being able to quickly make eye jumps from one target to
another (saccades) are two important elements for the success of neurosurgery.
The captured gaze patterns can be used to improve medical education, as part of
an assessment system or in a gaze-training application.
PMID- 28424916
TI - Bilateral pallidotomy for Meige syndrome.
AB - Meige syndrome (MS) is usually described as a combination of blepharospasm with
oromandibular dystonia. There are a large number of case reports of deep brain
stimulation (DBS) of the globus pallidus internus (GPI) for MS and only one
report of unilateral pallidotomy (PT). We report the first case of staged
bilateral PT for treatment of a patient with MS using intraoperative high
frequency stimulation in order to predict and prevent postoperative deficit.
There was a significant improvement of the Burk-Fahn-Marsden dystonia rating
scale from 26 to 3. There were no adverse postoperative neurological and
neuropsychological events.
PMID- 28424917
TI - Cubital tunnel syndrome caused by ganglion cysts: a review of 59 cases.
AB - BACKGROUND: Cubital tunnel syndrome caused by ganglion cysts is rare and reports
are few. This study aimed to review a patient cohort with ganglion cysts in the
cubital tunnel and identify prognostic factors. METHODS: Fifty-seven patients (59
extremities; McGowan grade I, 4; IIa, 4; IIb, 3; III, 48) were evaluated
retrospectively with a minimum follow-up of 2 years. Extraneural cysts were
excised completely, while intraneural cysts were incised and drained. All cases
underwent subcutaneous transposition. Spearman's rank correlation and the ordinal
logistic regression model were used to assess the effect of independent variables
on the postoperative McGowan grade. RESULTS: VAS pain and weakness, 2-PD, key
pinch strength, grip strength, first dorsal interosseous muscle strength,
Wartenberg sign, and claw hand all improved significantly. DASH scores improved
from an average of 43.8 points preoperatively to 10.7 points postoperatively.
According to the modified Bishop scoring system, 55 extremities (93.2%) were
graded good or excellent. At the last follow-up, 29 hands (49.2%) returned to
normal, and improvement by at least one McGowan grade was reached in 51 cases
(86.4%). Older age, smoking, and shorter postoperative follow-up were associated
with a higher postoperative McGowan grade. CONCLUSIONS: Satisfactory surgical
outcomes could be expected in these patients following subcutaneous transposition
with excision of extraneural cysts and draining of intraneural cysts. Older age,
smoking, and shorter postoperative follow-up were found to be independent risk
factors for poor outcomes.
PMID- 28424918
TI - Risk factors for surgical site infections among 1,772 patients operated on for
lumbar disc herniation: a multicentre observational registry-based study.
AB - BACKGROUND: There are no previous studies evaluating risk factors for surgical
site infections (SSIs) and the effectiveness of prophylactic antibiotic treatment
(PAT), specifically for patients operated on for lumbar disc herniation. METHOD:
This observational multicentre study comprises a cohort of 1,772 consecutive
patients operated on for lumbar disc herniation without laminectomy or fusion at
23 different surgical units in Norway. The patients were interviewed about SSIs
according to a standardised questionnaire at 3 months' follow-up. RESULTS: Three
months after surgery, 2.3% of the patients had an SSI. Only no PAT (OR = 5.3, 95%
CI = 2.2-12.7, p< 0.001) and longer duration of surgery than the mean time (68
min) (OR = 2.8, 95% CI = 1.2-6.6, p = 0.02) were identified as independent risk
factors for SSI. Numbers needed to have PAT to avoid one SSI was 43. CONCLUSIONS:
In summary, this study clearly lends support to the use of PAT in surgery for
lumbar disc herniation. Senior surgeons assisting inexperienced colleagues to
avoid prolonged duration of surgery could also reduce the occurrence of SSI.
PMID- 28424919
TI - Nerve enlargement in an unusual case of inflammatory neuropathy and new gene
mutation-morphology is the key.
PMID- 28424920
TI - Epidemiological information of dementia with Lewy bodies.
PMID- 28424921
TI - Evolution of psychological condition in caregivers of patients with disorders of
consciousness: a longitudinal study.
AB - The aim of this study is to evaluate mood disorders and needs in caregivers of
disorders of consciousness (DOC) patients during the admission to
Neurorehabilitation Unit. A total of 80 caregivers was enrolled and divided in
two groups (caregivers of vegetative state-VS patients and caregivers of
minimally conscious state-MCS patients). Paired sample t tests were carried out
to test differences between baseline observation (T0) and after 6 months (T1).
Caregivers of VS patients showed an improvement between T0 and T1 especially, in
vitality, mean health, Beck Depression Inventory (BDI-II), Spielberger State
Trait Anxiety Inventory-Y (STAI-Y), Prolonged Grief Disorder (PG 12) and
Caregiver Needs Assessment (CNA). On the other hand, caregivers of MCS patients
showed a significant improvement in: BDI II, STAI Y and CNA. These data confirmed
that the presence of psychological problems, the quality of life and the
psychological wellbeing of caregivers of DOC patients improved over the time.
PMID- 28424922
TI - Assistive technology for ultrasound-guided central venous catheter placement.
AB - This study evaluated the existing technology used to improve the safety and ease
of ultrasound-guided central venous catheterization. Electronic database searches
were conducted in Scopus, IEEE, Google Patents, and relevant conference databases
(SPIE, MICCAI, and IEEE conferences) for related articles on assistive technology
for ultrasound-guided central venous catheterization. A total of 89 articles were
examined and pointed to several fields that are currently the focus of
improvements to ultrasound-guided procedures. These include improving needle
visualization, needle guides and localization technology, image processing
algorithms to enhance and segment important features within the ultrasound image,
robotic assistance using probe-mounted manipulators, and improving procedure
ergonomics through in situ projections of important information. Probe-mounted
robotic manipulators provide a promising avenue for assistive technology
developed for freehand ultrasound-guided percutaneous procedures. However, there
is currently a lack of clinical trials to validate the effectiveness of these
devices.
PMID- 28424923
TI - Shear wave velocity of the healthy thyroid gland in children with acoustic
radiation force impulse elastography.
AB - PURPOSE: Acoustic radiation force impulse imaging is a kind of shear wave
elastography that can be used in children for differentiating thyroid
pathologies. Possible changes in the healthy thyroid gland in children may create
difficulties in the use of shear wave velocities (SWV) in thyroid pathologies.
The aim of this study was to define the normal values of SWV for the healthy
thyroid gland in children, elucidate the correlation of the SWV values with
potential influencing factors, and evaluate intra-operator reproducibility of the
SWV. METHODS: Between January 2015 and December 2015, a total of 145 healthy
children (81 girls, 64 boys; mean age, 10.5 +/- 3.14 years; range 6-17 years)
were enrolled in the study. The SWV and volume of the thyroid gland were
determined. RESULTS: The mean shear wave velocity of the thyroid gland was 1.22
+/- 0.20 m/s. There was no correlation between age and the mean SWV of the
thyroid gland (Spearman Rho = 0.049, p = 0.556). There was also no correlation
between the thyroid gland volume or BSA and the mean SWV. The only correlation
detected was between BSA and total thyroid gland volume (p < 0.001). CONCLUSION:
In the present study, the SWV of the healthy thyroid gland in children was
determined. There was no correlation between the SWV of the thyroid gland and
age, BSA, or thyroid gland volume.
PMID- 28424924
TI - Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1)
analog fusion protein, on CHO recombinant cells and BKS-db mice.
AB - AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes
mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which
limits its clinical application. The purpose of this study was to evaluate the
effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by
linking the human GLP-1 analog C-terminus to the N-terminus of human serum
albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether
GW002 can activate the GLP-1 receptor in cells, the level of luciferase
expression was evaluated in vitro. In vivo, body weight, food intake, non-fasting
and fasting blood glucose, oral glucose tolerance test, blood glucose and insulin
levels, liver histology, liver function parameters and antibody levels in BKS-db
mice were investigated to evaluate the effects of GW002. Albiglutide was chosen
as a positive comparator. RESULTS: Cyclic adenosine monophosphate levels were
increased in a dose-dependent manner in cells. In vivo studies demonstrated that
GW002 lowers non-fasting and fasting blood glucose levels and improves glucose
tolerance and insulin secretion in BKS-db mice. The degree of hepatic steatosis
and hepatic biochemical indexes was also decreased. In this study, the mice body
weight was not reduced significantly. CONCLUSIONS: The above results showed that
the efficacy of GW002 in BKS-db mice displayed a significant hypoglycemic effect,
which indicated that GW002 might be a potential candidate for the treatment of
T2DM.
PMID- 28424925
TI - Cross Vertical Mattress Suturing with Basilar Tightening During the Correction of
Inverted Nipple in 30 Cases.
AB - OBJECTIVE: To investigate the efficacy of cross vertical mattress suturing with
basilar tightening during the correction of inverted nipple. METHODS: Thirty
patients with inverted nipples underwent cross vertical mattress suturing with
basilar tightening. The postoperative results were recorded. RESULTS: All the
patients were followed up for 6 months to 2 years. The results of 28 cases were
satisfactory, and there was no recurrence. Two patients relapsed, and a mild
depression was formed. They were satisfied with the results after the second
correction. CONCLUSION: The method of cross vertical mattress suturing with
basilar tightening has been applied to treat inverted nipple, with minimal
trauma, which provides a reliable guarantee for a long-term effect. It is worthy
to be widely used in clinical practice. LEVEL OF EVIDENCE IV: This journal
requires that authors assign a level of evidence to each article. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 28424926
TI - Erratum to: Co2/Erbium:YAG/Dye Laser Combination: An Effective and Successful
Treatment for Angiofibromas in Tuberous Sclerosis.
PMID- 28424927
TI - Development of new extra-glandular manifestations or associated auto-immune
diseases after establishing the diagnosis of primary Sjogren's syndrome : A long
term study of the Antonius Nieuwegein Sjogren (ANS) cohort.
AB - To investigate in a long-term study, the development of new extra-glandular
manifestations (EGM) or associated auto-immune diseases (AID) from 1 year after
establishing the diagnosis of primary Sjogren's syndrome (pSS). The primary goal
was to examine the frequency and type of these manifestations and to find out
which demographic, clinical and serological profile was most at risk. All
outpatients diagnosed with primary Sjogren's syndrome were included in a
retrospective study, with at least one check-up per year, from June 1991 until
August 2015. Patients also fulfilling the criteria for concomitant connective
tissue disorders were excluded. Data were collected with respect to the
cumulative prevalence of a new EGM or associated AID. 140 patients were included
in the final analysis. After 10 years of follow-up, the cumulative incidence of a
new EGM or associated AID was 30.7%. The most frequent events were
polyneuropathy, interstitial lung disease, (poly)arthritis, discoid lupus
erythematosus (LE)/subacute cutaneous LE and Hashimoto's disease. Non-Hodgkin
lymphoma was not diagnosed during the follow-up. Patients without chronic benign
pain syndrome (CBP) (HR 2.13; 95% CI [0.94-4.76]; p = 0.061), but in particular
those with cryoglobulins (HR 2.87; 95% CI [1.20-6.86]; p = 0.013), developed more
events. Age at diagnosis, gender, the presence of ANA, anti-Ro/SSA, anti-La/SSB,
IgM-RF, decreased levels of C3 or C4, or hypergammaglobulinaemia did not show any
statistically significant differences. The burden of disease in pSS is higher
than expected due to the development of EGM or associated AID. Therefore, we
recommend long-term follow-up of all pSS patients, particularly those with
cryoglobulinaemia.
PMID- 28424928
TI - Metal-metal bonding in 1st, 2nd and 3rd row transition metal complexes: a
topological analysis.
AB - A topological analysis based on density functional electronic and spin densities
of the bonding characteristics in a series of Fe, Ru, Os, Tc and Rh dimers and
trimers bridged, respectively, by MU-1,8-naphthyridine (nap) and MU-2,2'
dipyridylamine (dpa) is presented. By this simple qualitative analysis, we were
able to determine the electronic ground state and correlated bonding order for a
number of complexes potentially involved in extended metal atom chains (EMAC).
Furthermore, we showed in the Ru dimer that it was possible to control the spin
state simply by changing the bonded counter-anion. Graphical Abstract Electron
localization analysis of the bonding properties in [M2(nap)4Cl2]2+ and
[M3(dpa)4(Cl2] complexes.
PMID- 28424929
TI - Assessment of TDDFT- and CIS-based methods for calculating fluorescence spectra
of (dibenzoylmethanato)boron difluoride exciplexes with aromatic hydrocarbons.
AB - The applicabilities of various CIS- and TDDFT-based procedures to the calculation
of the fluorescence spectra of DBMBF2 exciplexes with aromatic hydrocarbons are
analyzed. It is shown that a reasonable agreement between the calculated and
experimental fluorescence spectra is obtained when a combined procedure is used.
In this combined procedure, the geometries of the exciplexes are optimized
beforehand using the CIS method with an empirical dispersion correction, while
the exciplex transition energies are calculated at the optimized geometries using
the CIS(D) method or the TDDFT approach with double-hybrid B2PLYP and mPW2PLYP
functionals.
PMID- 28424930
TI - Comparison of laparoscopic hernia repair and open herniotomy in children: a
retrospective cohort study.
AB - BACKGROUND: Laparoscopic hernia repair in infancy and childhood is still
debatable. The objective of this study is to compare laparoscopic-assisted hernia
repair (LH) versus open herniotomy (OH) as regards operative time, postoperative
complications, recurrence rate, and contralateral metachronous hernia rate.
METHODS: We analyzed all the patients with inguinal hernia who underwent surgery
in our hospital from January 1, 2015 to December 31, 2015. There were 1125
patients, of which 202 patients received laparoscopic inguinal hernia repair
(group A) and 923 patients received open herniotomy (group B). We recalled all
the patients' records to identify operative time, postoperative hydrocele
formation, and contralateral patent processus vaginalis (CPP) detection; we
recalled all the patients' parents to identify the ipsilateral and contralateral
recurrence and the testis position. RESULTS: During the study period, the lost to
follow-up rate is 9.9% in group A and 14.1% in group B. The mean follow-up period
was about 10.1 months. The mean operative time for females with bilateral hernia
in group A was much shorter than that for those in group B (P = 0.001). The
postoperative hydrocele formation rate in group A was 1.5%, compared with 8.2% in
group B (P = 0.001). The recurrence rate was 0.64% in group A, whereas in group B
the recurrence rate was 0.46%. Of patients with unilateral hernia, none in group
A experienced a contralateral metachronous hernia (MH) compared with 10.1% in
group B (P < 0.001) and 65% MH appeared in 3 months after the first hernia
repair. Females and patients with initial left-sided hernia tended to have a
contralateral MH after the first open hernia repair. CONCLUSION: Laparoscopic
hernia repair in children is safe and effective, especially for female patients
and patients with initial left-sided hernia. We recommend repairing the CPP
simultaneously when performing laparoscopic procedures.
PMID- 28424931
TI - Contemporary engagement with social media amongst hernia surgery specialists.
AB - PURPOSE: Healthcare professional engagement is increasing. This study aims to
identify levels of adoption and engagement of several social media platforms by a
large international cohort of hernia surgery specialists. METHODS: Hernia
specialists attending the 38th International Congress of the European Hernia
Society were identified. A manual search was then performed on Twitter,
ResearchGate, and LinkedIn to identify those who had named accounts. Where
accounts were identified, data on markers of utilisation were assessed. RESULTS:
759 surgeons (88.5% male) from 57 countries were identified. 334 surgeons (44%)
engaged with a social media platform. 39 (5.1%) had Twitter accounts, 189 (24.9%)
had ResearchGate accounts and 265 (34.9%) had LinkedIn accounts. 137 surgeons
(18.1%) had accounts on 2 or more social media platforms. There was no gender
association with social media account ownership (p > 0.05). Engagement in one
social media platform was associated with increased engagement and utilisation on
other platforms; LinkedIn users were more likely to have Twitter accounts (p <
0.001) and ResearchGate profiles (p < 0.001). Surgeons on all three SM platforms
were more likely to have high markers of engagement across all SM platforms
(multiple outcomes, p < 0.05). Geographical variation was noted with UK and South
American Surgeons being more likely to be present on Twitter than their
counterparts (p = 0.031). CONCLUSIONS: The level of engagement with social media
amongst Hernia surgeons is similar to other surgical specialities. Geographical
variation in SM engagement is seen. Engagement with one SM platform is associated
with presence on multiple platforms.
PMID- 28424932
TI - Inverse relationship of Ca2+-dependent flagellar response between animal sperm
and prasinophyte algae.
AB - Symmetry/asymmetry conversion of eukaryotic flagellar waveform is caused by the
changes in intracellular Ca2+. Animal sperm flagella show symmetric or asymmetric
waveform at lower or higher concentration of intracellular Ca2+, respectively. In
Chlamydomonas, high Ca2+ induces conversion of flagellar waveform from asymmetric
to symmetry, resulting in the backward movement. This mirror image relationship
between animal sperm and Chlamydomonas could be explained by the distinct calcium
sensors used to regulate the outer arm dyneins (Inaba 2015). Here we analyze the
flagellar Ca2+-response of the prasinophyte Pterosperma cristatum, which shows
backward movement by undulating four flagella, the appearance similar to animal
sperm. The moving path of Pterosperma shows relatively straight in artificial
seawater (ASW) or ASW in the presence of a Ca2+ ionophore A23187, whereas it
becomes circular in a low Ca2+ solution. Analysis of flagellar waveform reveals
symmetric or asymmetric waveform propagation in ASW or a low Ca2+ solution,
respectively. These patterns of flagellar responses are completely opposite to
those in sperm flagella of the sea urchin Anthocidaris crassispina, supporting
the idea previously proposed that the difference in flagellar response to Ca2+
attributes to the evolutional innovation of calcium sensors of outer arm dynein
in opisthokont or bikont lineage.
PMID- 28424933
TI - Fact and controversies when assessing fluid responsiveness.
PMID- 28424934
TI - Synthesis, antioxidant and antimicrobial activities of novel thiopyrano[2,3
d]thiazoles based on aroylacrylic acids.
AB - Here it is described the synthesis, antioxidant and antimicrobial activity
determination of novel rel-([Formula: see text])-6-benzoyl-7-phenyl-2-oxo-3,5,6,7
tetrahydro-2H-thiopyrano[2,3-d]thiazole-5-carboxylic acids. The target compounds
were obtained in good yields from 5-arylidene-4-thioxo-2-thiazolidinones and
[Formula: see text]-aroylacrylic acids via regio- and diastereoselective hetero
Diels-Alder reaction. The stereochemistry of the cycloaddition was confirmed by
NMR spectra. The antioxidant and antimicrobial activity screening identified 7
compounds (3c, 3e, 3f, 3g, 3k, 3l, 3p) with a high level of free radical
scavenging (43-77% DPPH assay), and compounds with significant influence on
Staphylococcus aureus, Bacillus subtilis and Candida albicans (MIC 3.13-6.25
[Formula: see text]), but slight effect on Escherichia coli.
PMID- 28424935
TI - A Ratiometric and near-Infrared Fluorescent Probe for Imaging Cu2+ in Living
Cells and Animals.
AB - We have rationally constructed a novel ratiometric and near-infrared Cu2+
fluorescent probe based on a tricarbocyanine chromophore. The new probe NIR-Cu
showed a ratiometric fluorescent response to Cu2+ with a large emission
wavelength shift (up to 142 nm) in the far-red to near-infrared region. The probe
also displayed a large variation in the fluorescence ratio (I636/I778) to Cu2+
species with high sensitivity and selectivity. Additionally, the developed probe
NIR-Cu was suitable for fluorescence imaging of Cu2+ in living cells and mice.
PMID- 28424936
TI - Preoperative Chemoradiotherapy Versus Perioperative Chemotherapy for Patients
With Resectable Esophageal or Gastroesophageal Junction Adenocarcinoma.
AB - BACKGROUND: This study compares neoadjuvant chemoradiotherapy (nCRT) with
perioperative chemotherapy (pCT) for patients with resectable esophageal or
gastroesophageal junction (GEJ) adenocarcinoma in terms of toxicity,
postoperative complications, pathologic response, and survival. METHODS: This
study retrospectively analyzed and compared 313 patients with resectable
esophageal or GEJ adenocarcinoma treated with either nCRT (carboplatin/paclitaxel
41.4 Gy, n = 176) or pCT (epirubicin, cisplatin and capecitabine, n = 137).
RESULTS: The baseline and tumor characteristics were similar in both groups. The
ability to deliver all planned preoperative cycles was greater in the nCRT group
(92.0 vs. 76.6%). Whereas nCRT was associated with a higher rate of grades 3 and
4 esophagitis, pCT was associated with a higher rate of grades 3 and 4
thromboembolic events, febrile neutropenia, nausea, vomiting, diarrhea, hand-foot
syndrome, mucositis, cardiac complications, and electrolyte imbalances. Two
patients in the pCT group died during neoadjuvant treatment due to febrile
neutropenia. More postoperative cardiac complications occurred in the nCRT group.
All other postoperative complications and the in-hospital mortality rate (nCRT,
4.7%; pCT, 2.3%) were comparable. The pathologic complete response (pCR) rate was
15.1% after nCRT and 6.9% after pCT. Radicality of surgery was comparable (R0:
93.0 vs. 91.6%). The median overall survival was 35 months after nCRT versus 36
months after pCT. CONCLUSION: For patients with esophageal or GEJ adenocarcinoma,
chemoradiotherapy with paclitaxel, carboplatin and concurrent radiotherapy, and
perioperative chemotherapy with epirubicin, cisplatin, and capecitabin lead to
equal oncologic outcomes in terms of radical resection rates, lymphadenectomy,
patterns of recurrent disease, and (disease-free) survival. However, neoadjuvant
chemoradiotherapy is associated with a considerably lower level of severe adverse
events and should therefore be the preferred protocol until a well-powered
randomized controlled trial provides different insights.
PMID- 28424937
TI - Model to Predict Cause-Specific Mortality in Patients with Head and Neck Adenoid
Cystic Carcinoma: A Competing Risk Analysis.
AB - PURPOSE: The main objective of this study was to evaluate the cumulative
incidence of cause-specific death and other causes of death for patients with
head and neck adenoid cystic carcinoma (ACC). The secondary aim was to model the
probability of cause-specific death and build a competing risk nomogram to
predict cause-specific mortality for this disease. METHODS: Data were extracted
from the US National Cancer Institute's Surveillance Epidemiology, and End
Results (SEER)-18 dataset. The study cohort included patients with a diagnosis of
primary head and neck ACC during the period 2004-2013. We calculated the
cumulative incidence function (CIF) for cause-specific death and other causes of
death, and constructed the Fine and Gray's proportional subdistribution hazard
model, as well as a competing-risk nomogram based on Fine and Gray's model, to
predict the probability of cause-specific death for patients with head and neck
ACC. RESULTS: After data selection, 1435 cases were included for analysis. Five
year cumulative incidence of cause-specific death was 17.4% (95% confidence
interval [CI] 15.1-19.8%) and cumulative incidence of other causes of death was
5.8% (95% CI 4.4-7.4%). Predictors of cause-specific death for head and neck ACC
included age, tumor size, advanced T stage, positive lymph node, distant
metastasis, and surgery. The nomogram was well-calibrated, and had good
discriminative ability. CONCLUSION: The large sample allowed us to construct a
reliable predictive model for rare malignancy. The model performance was good,
with a concordance index of 0.79, and the nomogram can provide useful
individualized predictive information for patients with head and neck ACC.
PMID- 28424938
TI - Characterization and Genome Sequence of Marine Alteromonas gracilis Phage PB15
Isolated from the Yellow Sea, China.
AB - A novel marine Alteromonas gracilis siphovirus, phage PB15, was isolated from the
surface water of the Yellow Sea in August 2015. It has a head diameter of 58 +/-
5 nm head and a contractile tail approximately 105 +/- 10 nm in length, and
overall, the morphology suggests that PB15 belongs to the family Siphoviridae.
PB15 phage is stable at over the temperature range 0-60 degrees C. The best MOI
of these phage was 0.1, and infectivity decreased above 60 degrees C. The
results suggest that phage is stable at pH value ranging between 3.0 and 11.0.
Chloroform test shows that PB15 is not a lipid-containing phage. A one-step
growth curve with a strain of A. gracilis gave a latent period of 16 min and rise
period of 24 min and burst size of 60 PFU/cell. Genomic analysis of PB15 reveals
a genome size of 37,333 bp with 45.52% G+C content, and 61 ORFs. ORF sequences
accounted for 30.36% of the genome sequence. There is no obvious similarity
between PB15 and other known phages by genomic comparison using the BLASTN tool
in the NCBI database.
PMID- 28424939
TI - Characterization and Complete Genome Sequence of a Novel Siphoviridae
Bacteriophage BS5.
AB - A novel Siphoviridae family Phage BS5, which infects Pseudoalteromonas atlantica,
was isolated from the surface waters of the Yellow Sea. Morphological study by
transmission electron microscopy revealed that the novel phage belongs to
Siphoviridae. The complete genome sequence of PBS5 contained a linear, double
strand 39949-bp DNA molecule with a G + C content of 40.6% and 65 putative open
reading frames. Twelve conserved domains were detected by BLASTP in NCBI, and of
these the functions of 5 were known. The genome was grouped into four modules as
follows: phage structure, phage packaging, DNA replication and regulation, and
some additional functions.16 S rDNA sequence analysis was also applied to
identify the host bacteria. After initial characterization of bacteriophage PBS5,
it was found that the optimal pH was 7.0, the optimal temperature was 30 degrees
C, and the burst size was about 95 virions per cell. This information will
provide an important benchmark for further research on the interaction between
bacteriophages and their hosts.
PMID- 28424940
TI - Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of
Escherichia coli Mutants.
AB - Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has
become of great concern. The effect of some widely used food additives such as
sucralose on bacteria in the gut and the environment has also drawn increasing
attention. In this study, we investigated the interaction between antimicrobials
and sucralose impacting antimicrobial resistance and mutation of Escherichia coli
(E. coli). To examine antimicrobial resistance and mutation frequency, different
subinhibitory concentrations of sucralose were added to cultures of E.coli
BW25113 that were then treated with antimicrobials, oxolinic acid, or
moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of
mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of
E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose
increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of
sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72
h, while rifampicin-resistant mutation rate was increased when co-treated with
1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can
increase the antimicrobial resistance and mutation frequency of E.coli to some
antimicrobials.
PMID- 28424941
TI - Isolation and Complete Genome Sequence of a Novel Pseudoalteromonas Phage PH357
from the Yangtze River Estuary.
AB - Phage PH357, a novel lytic Pseudoalteromonas lipolytica phage belonging to the
Myoviridae family was isolated from the Yangtze River estuary. The
microbiological characterization demonstrated that phage PH357 is stable from -20
to 60 degrees C and the optimal pH 7. The one-step growth curve showed a latent
period of 20 min, a rise period of 20 min, and the average burst size was about
85 virions per cell. Complete genome of phage PH357 was determined. Genome of
phage PH357 consisted of a linear, double-stranded 136,203 bp DNA molecule with
34.58% G + C content, and 242 putative open reading frames (ORFs) without tRNA.
All the predicted ORFs were classified into eight functional groups, including
DNA replication, regulation and nucleotide metabolism, transcription,
translation, phage packaging, phage structure, lysis, host or phage interactions,
and hypothetical protein. A phylogenetic analysis showed that phage PH357 had
similarity to the previously published Pseudoalteromonas phage PH101 and Vibrio
phages. Furthermore, the study of phage PH357 genome will provide useful
information for further research on the interaction between phages and their
hosts.
PMID- 28424942
TI - Serratia bozhouensis sp. nov., Isolated from Sewage Samples of a Dairy Farm.
AB - A Gram-negative, rod-shaped, salt-tolerant, non-pigmented, and non-spore-forming
bacterium, designated strain W1T (type strain CICC 23797 = CGMCC1.14949), was
isolated from sewage samples of a dairy farm in Bozhou, Anhui, China. Strain W1
was resistant to lincomycin, troleandomycin, rifamycin, and vancomycin. Sequence
analysis of the 16S rDNA gene revealed that the strain showed sequence similarity
of 98.2% with the closest related species Serratia quinivorans CP6aT. The genomic
DNA G+C content of the isolate was 52.8 mol%. The biochemical characteristics of
strain W1T assessed by the API 20E and Biolog GEN III analysis were different
from those of the members of the genus Serratia. On the basis of the phenotypic
and genotypic differences, strain W1 was proposed to be a novel Serratia species,
Serratia bozhouensis sp. nov W1T.
PMID- 28424944
TI - Indirect interactions between arbuscular mycorrhizal fungi and Spodoptera exigua
alter photosynthesis and plant endogenous hormones.
AB - Peanut (Arachis hypogaea Linn. cv: Luhua 11) and tomato (Lycopersicon esculentum
Mill. cv: Zhongshu 4) were inoculated with arbuscular mycorrhizal fungi (AMF)
Funneliformis mosseae BEG167 (Fm), Rhizophagus intraradices BEG141 (Ri), and
Glomus versiforme Berch (Gv), and/or Spodoptera exigua (S. exigua) under
greenhouse conditions. Results indicated that feeding by S. exigua had little
influence on colonization of peanut plants by AMF, but improved colonization of
tomato by Fm and Gv. Feeding by S. exigua had little influence on leaf net
photosynthetic rate, transpiration rate, and stomatal conductance of
nonmycorrhizal peanut plants but significantly improved net photosynthetic rate
and transpiration rate of mycorrhizal plants of both hosts. AMF with or without
S. exigua inoculation improved host plant photosynthetic characteristics, growth,
and hormone status. Fm showed maximum beneficial effects, followed by Gv. The
concentrations and ratios of phytohormones abscisic acid (ABA), indole-3-acetic
acid (IAA), gibberellin (GA), zeatin riboside (ZR), and jasmonic acid (JA) in the
leaves of the host plants were changed due to the interaction between AMF and S.
exigua. Generally, AMF with or without S. exigua inoculation increased the
concentrations of GA, ZR, and JA and the ratios of IAA/ABA, GA/ABA, ZR/ABA, and
IAA + GA + ZR/ABA, while feeding by S. exigua on nonmycorrhizal plants showed the
opposite effect. The concentration of JA in the leaves of peanut and tomato
inoculated with Fm or Fm + S. exigua was 1.9 and 1.9 times and 2.5 and 2.7 times,
respectively, greater than that of the controls inoculated with neither. There
was a negative correlation between the JA concentration and the survival
percentage of S. exigua larva. We conclude that indirect interactions between AMF
and insect herbivores changed the photosynthetic and hormone characteristics, and
ratios of phytohormones, thereby revealing mechanisms of belowground-aboveground
interactions.
PMID- 28424943
TI - Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in
Mice.
AB - BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role
in the activation of inflammatory pathways in the liver and in the pathogenesis
of alcoholic liver disease. The intestinal brush-border enzyme intestinal
alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory
factors and also functions to preserve gut barrier function. The aim of this
study was to investigate whether oral IAP supplementation could protect against
alcohol-induced liver disease. METHODS: Mice underwent acute binge or chronic
ethanol exposure to induce alcoholic liver injury and steatosis +/- IAP
supplementation. Liver tissue was assessed for biochemical, inflammatory, and
histopathological changes. An ex vivo co-culture system was used to examine the
effects of alcohol and IAP treatment in regard to the activation of hepatic
stellate cells and their role in the development of alcoholic liver disease.
RESULTS: Pretreatment with IAP resulted in significantly lower serum alanine
aminotransferase compared to the ethanol alone group in the acute binge model.
IAP treatment attenuated the development of alcohol-induced fatty liver, lowered
hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol
induced gut barrier dysfunction. Finally, IAP ameliorated the activation of
hepatic stellate cells and prevented their lipogenic effect on hepatocytes.
CONCLUSIONS: IAP treatment protected mice from alcohol-induced hepatotoxicity and
steatosis. Oral IAP supplementation could represent a novel therapy to prevent
alcoholic-related liver disease in humans.
PMID- 28424945
TI - Date palm waste biochars alter a soil respiration, microbial biomass carbon, and
heavy metal mobility in contaminated mined soil.
AB - A 30-day incubation experiment was conducted using a heavy metal-contaminated
mined soil amended with date palm feedstock (FS) and its derivative biochars
(BCs) at three pyrolysis temperatures of 300 (BC-300), 500 (BC-500), and 700
degrees C (BC-700) with different application rates (0.0, 5, 15, and 30 g kg-1)
to investigate their short-term effects on soil respiration (CO2-C efflux),
microbial biomass carbon (MBC), soil organic carbon (SOC), mobile fraction of
heavy metals (Cd, Cu, Pb, Zn, Mn, and Fe), pH, and electrical conductivity (EC).
The results showed that FS and BC-300 with increasing addition rate significantly
reduced soil pH, whereas SOC, CO2-C efflux, and soil MBC were increased compared
to the control. On the contrary, BC-500 and BC-700 increased soil pH at early
stage of incubation and have small or no effects on SOC, CO2-C efflux, and MBC.
Based on the results, the date palm biochars exhibited much lower cumulative CO2
C efflux than feedstock, even with low-temperature biochar, indicating that BCs
have C sequestration potential. Applying BC-700 at 15 and 30 g kg-1 significantly
reduced cumulative CO2-C efflux by 21.8 and 45.4% compared to the control,
respectively. The incorporation of FS into contaminated soil significantly
increased the mobile content of Cd and Mn, but decreased the mobile content of
Cu. However, BC-300 significantly reduced the mobile content of Cd, Cu, Pb, and
Zn. It could be concluded that low-temperature biochar could be used as a soil
amendment for reducing heavy metal mobility in mining contaminated soil in
addition to minimize soil CO2-C efflux.
PMID- 28424946
TI - Preparation and corrosion resistance of magnesium phytic acid/hydroxyapatite
composite coatings on biodegradable AZ31 magnesium alloy.
AB - In this work, a magnesium phytic acid/hydroxyapatite composite coating was
successfully prepared on AZ31 magnesium alloy substrate by chemical conversion
deposition technology with the aim of improving its corrosion resistance and
bioactivity. The influence of hydroxyapatite (HA) content on the microstructure
and corrosion resistance of the coatings was investigated. The results showed
that with the increase of HA content in phytic acid solution, the cracks on the
surface of the coatings gradually reduced, which subsequently improved the
corrosion resistance of these coated magnesium alloy. Electrochemical
measurements in simulated body fluid (SBF) revealed that the composite coating
with 45 wt.% HA addition exhibited superior surface integrity and significantly
improved corrosion resistance compared with the single phytic acid conversion
coating. The results of the immersion test in SBF showed that the composite
coating could provide more effective protection for magnesium alloy substrate
than that of the single phytic acid coating and showed good bioactivity.
Magnesium phytic acid/hydroxyapatite composite, with the desired bioactivity, can
be synthesized through chemical conversion deposition technology as protective
coatings for surface modification of the biodegradable magnesium alloy implants.
The design idea of the new type of biomaterial is belong to the concept of "third
generation biomaterial". Corrosion behavior and bioactivity of coated magnesium
alloy are the key issues during implantation. In this study, preparation and
corrosion behavior of magnesium phytic acid/hydroxyapatite composite coatings on
magnesium alloy were studied. The basic findings and significance of this paper
are as follows: 1. A novel environmentally friendly, homogenous and crack-free
magnesium phytic acid/hydroxyapatite composite coating was fabricated on AZ31
magnesium alloy via chemical conversion deposition technology with the aim of
enhancing its corrosion resistance and bioactivity. The chemical conversion
coatings, which are formed through the reaction between the substrate and the
environment, have attracted increasing attention owing to the relative low
treatment temperature, favorable bonding to substrate and simple implementation
process. 2. With the increasing of hydroxyapatite (HA) content, the crack width
in the composite coatings and the thickness of the coatings exhibit obviously
decreased. The reason is probably that when adding HA into the phytic acid
solution, the amount of active hydroxyl groups in the phytic acid are reduced via
forming the coordination bond between P-OH groups from phytic acid and P-OH
groups from the surface of HA, thus decreasing the coating thickness and hydrogen
formation, as well as avoiding coating cracking. 3. By adjusting the HA content
to 45 wt.%, a dense and relatively smooth composite coating with ~1.4 MUm
thickness is obtained on magnesium alloy, and exhibits high corrosion resistance
and good bioactivity when compared with the single phytic acid conversion
coating.
PMID- 28424947
TI - Neurodevelopmental Effects of Antiepileptic Drugs.
AB - Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs)
during critical periods of development may induce transient or long-lasting
neurodevelopmental deficits across cognitive, motor and behavioral domains. The
developing nervous system may endure prolonged chronic exposure to AEDs during
pregnancy (in utero) or during childhood, which can lead to neurodevelopmental
defects such as congenital neural tube defects, lower IQ, language deficits,
autism and ADHD. To date, valproate is the most widely recognized AED to
significantly negatively affect neurodevelopment, and demonstrates greater
adverse effects than any other AEDs that have been assessed. Although some AEDs
appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been
implicated in a variety of studies detailed below, and many AEDs have not been
adequately assessed. The purpose of this review article is to summarize our
current understanding of the neurodevelopmental effects of AEDs.
PMID- 28424948
TI - 14-3-3 Isoforms Differentially Regulate NFkappaB Signaling in the Brain After
Ischemia-Reperfusion.
AB - Mammalian 14-3-3 isoforms exist predominantly in the brain and are heavily
involved in neurological diseases. However, the isoform-specific role of 14-3-3
proteins in the brain remains largely unclear. Here, we investigated the role of
14-3-3 isoforms in rat brains after transient middle cerebral artery occlusion
and reperfusion. 14-3-3beta, eta, gamma and zeta but not epsilon or tau were
selectively upregulated in cerebral cortical neurons after ischemia-reperfusion
(I/R). Selectively, 14-3-3beta, gamma and zeta were translocated from cytoplasm
into the nuclei of neurons after I/R. 14-3-3 bound to p65 and suppressed p65
expression in N2a cells. In the brain, 14-3-3 could either colocalize with p65 in
the nuclei of neurons or segregate from p65 expression in cortical neurons after
I/R. All evidence together suggests that 14-3-3 isoforms are differentially
induced to enter into the nuclei of neurons after I/R, which might regulate
NFkappaB signaling directly or indirectly. Since 14-3-3 proteins are essential
for cell survival and NFkappaB is a key transcriptional factor, our data suggest
that the 14-3-3/p65 signaling pathway might be a potential therapeutic target for
stroke.
PMID- 28424950
TI - Estimated work ability in warm outdoor environments depends on the chosen heat
stress assessment metric.
AB - With a view to occupational effects of climate change, we performed a simulation
study on the influence of different heat stress assessment metrics on estimated
workability (WA) of labour in warm outdoor environments. Whole-day shifts with
varying workloads were simulated using as input meteorological records for the
hottest month from four cities with prevailing hot (Dallas, New Delhi) or warm
humid conditions (Managua, Osaka), respectively. In addition, we considered the
effects of adaptive strategies like shielding against solar radiation and
different work-rest schedules assuming an acclimated person wearing light work
clothes (0.6 clo). We assessed WA according to Wet Bulb Globe Temperature (WBGT)
by means of an empirical relation of worker performance from field studies
(Hothaps), and as allowed work hours using safety threshold limits proposed by
the corresponding standards. Using the physiological models Predicted Heat Strain
(PHS) and Universal Thermal Climate Index (UTCI)-Fiala, we calculated WA as the
percentage of working hours with body core temperature and cumulated sweat loss
below standard limits (38 degrees C and 7.5% of body weight, respectively)
recommended by ISO 7933 and below conservative (38 degrees C; 3%) and liberal
(38.2 degrees C; 7.5%) limits in comparison. ANOVA results showed that the
different metrics, workload, time of day and climate type determined the largest
part of WA variance. WBGT-based metrics were highly correlated and indicated
slightly more constrained WA for moderate workload, but were less restrictive
with high workload and for afternoon work hours compared to PHS and UTCI-Fiala.
Though PHS showed unrealistic dynamic responses to rest from work compared to
UTCI-Fiala, differences in WA assessed by the physiological models largely
depended on the applied limit criteria. In conclusion, our study showed that the
choice of the heat stress assessment metric impacts notably on the estimated WA.
Whereas PHS and UTCI-Fiala can account for cumulative physiological strain
imposed by extended work hours when working heavily under high heat stress, the
current WBGT standards do not include this. Advanced thermophysiological models
might help developing alternatives, where not only modelling details but also the
choice of physiological limit criteria will require attention. There is also an
urgent need for suitable empirical data relating workplace heat exposure to
workability.
PMID- 28424949
TI - Aggressive Crosstalk Between Fatty Acids and Inflammation in Macrophages and
Their Influence on Metabolic Homeostasis.
AB - From the immunological point of view, macrophages are required to maintain
metabolic homeostasis. Recently, there has been an increased focus on the
influence of macrophage phenotypes in adipose tissue on the maintenance of
metabolic homeostasis in healthy conditions because dysregulated metabolic
homeostasis causes metabolic syndrome. This review notes several types of
inflammatory and anti-inflammatory mediators in metabolic homeostasis. M1
macrophage polarization mediates inflammation, whereas M2 macrophage polarization
mediates anti-inflammation. Fatty acids and their related factors mediate both
inflammatory and anti-inflammatory responses. Saturated fatty acids and
polyunsaturated fatty acids mediate inflammation, whereas marine-derived n-3
fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, mediate anti
inflammation. In this review, we discuss the current understanding of the
crosstalk between fatty acids and inflammation in macrophages and their influence
on metabolic homeostasis.
PMID- 28424951
TI - Influence of Genetic Counseling Graduate Program Websites on Student Application
Decisions.
AB - This study investigated how genetic counseling educational program websites
affect application decisions via an online survey sent to current students and
recent graduates. Program leadership: directors, assistant directors, associate
directors, were also surveyed to determine where their opinions coincided or
differed from those reported by students and recent graduates. Chi square
analysis and t-tests were used to determine significance of results. A two-sample
t-test was used to compare factors students identified as important on a 5-point
Likert scale with those identified by directors. Thematic analysis revealed three
major themes students consider important for program websites: easy navigation,
website content, and website impression. Directors were interested in how
prospective students use their program website and what information they found
most useful. Students indicated there were specific programs they chose not to
apply to due to the difficulty of using the website for that program. Directors
significantly underestimated how important information about application
requirements was to students in making application decisions. The information
reported herein will help individual genetic counseling graduate programs improve
website functionality and retain interested applicants.
PMID- 28424952
TI - Preadolescents' Emotional and Prosocial Responses to Negative TV News:
Investigating the Beneficial Effects of Constructive Reporting and Peer
Discussion.
AB - Watching news is important for preadolescents, but it may also harm their well
being. This study examined whether applying insights from positive psychology to
news production can reduce this potential harm, by reducing negative emotional
responses and enhancing positive emotional responses to negative news, and by
encouraging prosocial intentions. Moreover, we explored whether peer discussion
strengthened these effects. Preadolescents (n = 336; 9-13 years old; 48.5%
female) were exposed to either constructive (solution-based news including
positive emotions) or nonconstructive news. Subsequently, half of the children
assigned to the constructive and the nonconstructive condition participated in a
peer discussion. The findings showed that exposure to constructive news resulted
in more positive emotional responses and less negative emotional responses as
compared to nonconstructive news. Moreover, discussing the news with peers led to
more positive and less negative emotional responses among preadolescents who
watched the nonconstructive newscast, and to more prosocial intentions among
preadolescents who watched constructive news. In all, constructive news reporting
and peer discussion could function as tools to make negative news less harmful
for preadolescents.
PMID- 28424954
TI - Trendiness in human ARTs as technology transits from the macro to nano.
PMID- 28424955
TI - Erratum to: Study of plasma off-gas treatment from spent ion exchange resin
pyrolysis.
PMID- 28424953
TI - Treatment Update of Chronic Migraine.
AB - PURPOSE OF REVIEW: Although chronic migraine (CM) is a common disorder that
severely impacts patient functioning and quality of life, it is usually
underdiagnosed, and treatment responses often remain poor even after diagnosis.
In addition, effective treatment options are limited due to the rarity of
randomized controlled trials (RCTs) involving patients with CM. In the present
review, we discuss updated pharmacological, non-pharmacological, and
neurostimulation treatment options for CM. RECENT FINDINGS: Pharmacological
treatments include both acute and preventive measures. While acute treatment
options are similar between CM and episodic migraine (EM), preventive treatment
with topiramate and botulinum toxin A exhibited efficacy in more than two RCTs.
In addition, several studies have revealed that behavioral interventions such as
cognitive behavioral therapy, biofeedback, and relaxation techniques are
associated with significant improvements in symptoms. Thus, these treatment
options are recommended for patients with CM, especially for refractory cases.
Neurostimulation procedures, such as occipital stimulation, supraorbital
transcutaneous stimulation, non-invasive vagal nerve stimulation, and
transcranial direct current stimulation, have shown promising results in the
treatment of CM. However, current studies on neurostimulation suffer from small
sample size, no replication, or negative results. Although CM is less responsive
to treatment compared to EM, recent advance in pharmacological, non
pharmacological, and neurostimulation treatments may provide more chance for
successful treatment of CM.
PMID- 28424956
TI - Removal of selected pesticides from groundwater by membrane distillation.
AB - The removal of five selected pesticide compounds in a brackish model groundwater
solution was examined using a bench scale direct contact membrane distillation
(DCMD) system. It was found that the rejection rate of the pesticides in DCMD is
mainly influenced by its properties. Compounds with low hydrophobic
characteristics and low vapour pressure showed a high rejection rate (70-99%),
whereas compounds with a high vapour pressure or high hydrophobicity (LogD)
showed a reduced rejection (30-50%) at a water recovery of 75%. The influence of
groundwater feed solution contents such as the presence of organics (humic acid)
and inorganic ions (Na+, Ca2+, Mg2+, Cl- and SO42-) as well as feed temperature
(40, 55 and 70 degrees C) on the rejection of the pesticides in DCMD operation
was also evaluated. The results showed that the presence of inorganic ions and
organics in the feed solution influences the pesticides rejection in DCMD
operation to a minor degree. In contrast, reduced rejection of pesticides with
high vapour pressure was observed. A rapid small-scale column test (RSSCT) was
carried out to study the removal of any remaining substances in the permeate by
adsorption onto granular activated carbon (GAC). RSSCT showed promising
performance of GAC as a post-treatment option.
PMID- 28424957
TI - Assessing PAHs pollution in Shandong coastal area (China) by combination of
chemical analysis and responses of reproductive toxicity in crab Portunus
trituberculatus.
AB - The concentrations of PAHs in seawater and sediments were measured at three
selected sites (S1, S2, and S3) along the coastal area of Shandong (China) in
April, May, and June, 2015, which ranged from 29.72 to 123.88 ng/L and 82.62 to
232.63 ng/g, respectively. Meanwhile, the reproductive toxicity responses in crab
Portunus trituberculatus were also evaluated to assess the pollution of PAHs
during the sampling period. Chemical analysis showed that S3 was the most PAH
contaminated area while S1 was the least, and the biochemical parameters
concerned with reproduction were efficiently responded to the three sites,
especially in S3 (p < 0.05). Moreover, the principal component analyses (PCA)
showed that parameters for DNA alkaline unwinding, protein carbonyl content, and
lipid peroxidation levels in two genders, 17beta-estradiol in female,
testosterone and TESK2 gene expression in male crabs, were closely correlated
with the concentrations of PAHs (2 + 3 rings, 4 rings, and 5 + 6 rings), which
were considered to be good candidate indicators to assess the environmental
pollutions resulting from PAHs in the coastal area of Shandong, China.
PMID- 28424958
TI - Effectiveness of waste prevention program in primary students' schools.
AB - Even though reducing waste is at the top of the waste hierarchy, no real
decoupling between waste generation and consumption has been demonstrated.
Several waste directives had been published from EU, but they have only brought
minor changes within the key objective of reducing waste generation. Most efforts
have been targeted towards greater amounts of recycling and better management of
waste disposal. While these are necessary and socially beneficial goals, they are
not adequate for the achievement of long-term sustainability goals. The purpose
of this study is to understand students' knowledge, attitudes and behavioural
changes in relation to the water plastic bottle of 500 ml. Understanding waste
prevention behaviour (WPB) could enable schools' principals, local authorities
and committees as well as decision makers to design and implement more effective
policies for reducing the amount of specific waste streams that is generated.
Students in a daily base bring their own water containers of 500 ml or buy water
from the school as they do not feel safe to use other sources of water. Nine
hundred ninety-eight refilling stainless steel water refilling bottles (SSWRB-of
600 ml) were shared to the students in four primary schools. The results
indicated that the students are presented with different behaviours from class to
class for many reasons; most of them are related with what their parents believe,
and how themselves or the synergies between them reacts and affected.
PMID- 28424959
TI - Non-essential element concentrations in brown grain rice: Assessment by advanced
data mining techniques.
AB - The concentrations of 17 non-essential elements (Al, As, Ba, Be, Cd, Ce, Cr, Hg,
La, Li, Pb, Sb, Sn, Sr, Th, Ti, and Tl) were determined in brown grain rice
samples of two varieties: Fortuna and Largo Fino. The samples were collected from
the four main producing regions of Corrientes province (Argentina). Quantitative
determinations were performed by inductively coupled plasma mass spectrometry
(ICP-MS), using a validated method. The contents of As, Be, Cd, Ce, Cr, Hg, Pb,
Sb, Sn, Th, and Tl were very low or not detected in most samples. The non
essential element levels detected were in line with studies conducted in rice
from different parts of the world. In order to characterize the influence of
geographical origin in the samples, the following classification methods were
carried out: linear discriminant analysis (LDA), k-nearest neighbors (k-NN),
partial least squares discriminant analysis (PLS-DA), support vector machine
(SVM) and random forests (RF). The best performance was obtained by using RF
(96%) and SVM (96%). The results reported here showed the variation in the non
essential element profiles in rice grain depending on the geographical origin.
PMID- 28424960
TI - Selenium for the mitigation of toxicity induced by lead in chicken testes through
regulating mRNA expressions of HSPs and selenoproteins.
AB - Lead (Pb) is a toxic element and environmental pollutant. Pb toxicity and
antagonistic effect of selenium (Se) on Pb have been deeply studied in mammals.
The testis is one of the target organs of Pb in birds. The aim of this study was
to investigate the mitigating effect of Se on Pb toxicity in chicken testes by
determining messenger RNA (mRNA) expressions of 5 heat shock proteins (HSPs) and
25 selenoproteins. Sixty male chickens (7-day-old) were randomly divided into the
control group, the Se group, the Pb group, and the Pb + Se group, and were fed
for 90 days. The feeding methods of chickens were as follows: The control group
was fed drinking water and commercial diet (0.49 mg/kg Se). Lead acetate was
added into the drinking water (350 mg/L Pb). Sodium selenite was added into the
commercial diet (1 mg/kg Se). Multivariate correlation analysis and principal
component analysis (PCA) were used to define the relationships among all the
measured factors and the most important parameters that could be used as key
factors, respectively. The results indicated that Se decreased the increase of
mRNA expressions of all the HSPs and increased the decrease of mRNA expressions
of all the selenoproteins induced by Pb in the chicken testes. HSP70 may be a
biomarker of Pb poisoning in the chicken testes. Se alleviated Pb-induced
toxicity in the chicken testes through regulating mRNA expressions of HSPs and
selenoproteins.
PMID- 28424961
TI - Tillandsia usneoides: A successful alternative for biomonitoring changes in air
quality due to a new highway in Sao Paulo, Brazil.
AB - Tillandsia usneoides is an aerial epiphytic bromeliad that absorbs water and
nutrients directly from the atmosphere by scales covering its surface. We
expanded the use of this species as a broader biomonitor based on chemical and
structural markers to detect changes in air quality. The usefulness of such
comprehensive approach was tested during the construction and opening of a
highway (SP-21) in Sao Paulo State, Brazil. The biomonitoring study was performed
from 2009 to 2012, thus comprising the period during construction and after the
highway inauguration. Metal accumulation and structural alterations were
assessed, in addition to microscopy analyses to understand the metal chelation in
plant tissues and to assess the causes of alterations in the number and shape of
scale cells. Altogether, our analyses support the use of this species as a wide
biomonitor of air quality in urbanized areas.
PMID- 28424962
TI - Phase I dose-escalation study of milciclib in combination with gemcitabine in
patients with refractory solid tumors.
AB - BACKGROUND: This phase I trial evaluated the safety and tolerability of
milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin
receptor kinase A, in combination with gemcitabine in patients with refractory
solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib
at three dose levels (45 mg/m2/day, n = 3; 60 mg/m2/day, n = 3; and 80 mg/m2/day,
n = 10) with a fixed dose of gemcitabine (1000 mg/m2/day). Milciclib was
administered orally once daily for 7 days on/7 days off in a 4-week cycle, and
gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle.
RESULTS: All 16 enrolled patients were evaluable for safety and toxicity. Dose
limiting toxicities, which occurred in only one out of nine patients treated at
the maximum dose tested (milciclib 80 mg/m2/day and gemcitabine 1000 mg/m2/day),
consisted of Grade 4 thrombocytopenia, Grade 3 ataxia and Grade 2 tremors in the
same patient. Most frequent treatment-related AEs were neutropenia and
thrombocytopenia. Among 14 evaluable patients, one NSCLC patient showed partial
response and 4 patients (one each with thyroid, prostatic, pancreatic carcinoma
and peritoneal mesothelioma) showed long-term disease stabilization (>6-14
months). Pharmacokinetics of the orally administered milciclib (~t1/2 33 h) was
not altered by concomitant treatment with gemcitabine. CONCLUSION: The
combination treatment was well tolerated with manageable toxicities. The
recommended phase II dose was 80 mg/m2/day for milciclib and 1000 mg/m2/day for
gemcitabine. This combination treatment regimen showed encouraging clinical
benefit in ~36% patients, including gemcitabine refractory patients. These
results support further development of combination therapies with milciclib in
advanced cancer patients.
PMID- 28424963
TI - Pharmacokinetics and safety of carfilzomib in patients with relapsed multiple
myeloma and end-stage renal disease (ESRD): an open-label, single-arm, phase I
study.
AB - PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in
multiple myeloma patients with varying degrees of renal impairment (normal, mild,
moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20
mg/m2. This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m2 in
normal renal function and ESRD patients. METHODS: Patients received carfilzomib
on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m2 (cycle 1
day 1-2), escalated to 27 mg/m2 on cycle 1 day 8; if tolerated, 56 mg/m2 starting
cycle 2 day 1. The primary objective was PK assessment with safety/tolerability
and response rate as secondary and exploratory objectives, respectively. RESULTS:
26 patients were enrolled (15 normal, 11 ESRD). There was a trend toward higher
area under the concentration time curve (AUC) and maximum concentration in ESRD
versus normal renal function patients; however, high interpatient PK variability
was discerned. Relative to patients with normal renal function, ESRD patients
showed 33% higher AUC. Overall response rate was 43% for the normal renal
function and 60% for the ESRD groups. Safety findings were generally similar
between the two groups and consistent with the known safety profile of
carfilzomib in multiple myeloma patients. CONCLUSION: There were no meaningful
differences in PK between patients with normal renal function and ESRD in light
of carfilzomib exposure-response relationships. These results continue to support
dosing recommendation that no starting dose adjustment of carfilzomib appears
warranted in patients with baseline renal impairment.
PMID- 28424964
TI - Pharmacodynamic effects in the cerebrospinal fluid of rats after intravenous
administration of different asparaginase formulations.
AB - PURPOSE: Asparaginase (ASNase) is used to treat various hematological
malignancies for its capacity to deplete asparagine (ASN) in serum and
cerebrospinal fluid (CSF). Since the biological mechanisms underlying CSF
asparagine depletion in humans are not yet fully elucidated, this study compared,
for the first time, the pharmacological properties of three clinically used
ASNase formulations in a rodent model. METHODS: Male Wistar rats were treated
with E.coli-ASNase, PEG-ASNase, or ERW-ASNase at different doses. Serum and CSF
amino-acid levels and ASNase activities were evaluated at 1 and 24 h after the
intravenous administration of different ASNase doses. RESULTS: All the ASNase
formulations showed higher activities in serum after 1 h than 24 h and completely
deplete ASN. Mean ASNase activity in the CSF at 1 h was higher with ERW-ASNase
compared to PEG-ASNase (36 +/- 29 vs 8 +/- 7 U/L, p < 0.037) and similar to
E.coli-ASNase (21 +/- 9 U/L, ns). ERW-ASNase and E.coli-ASNase at the highest
doses were able to deplete ASN in the CSF after 1 h. This effect was transient
and not evident at 24 h after treatment. CONCLUSIONS: Together with the ASN
depletion in serum and CSF, a never before demonstrated transient penetration of
ASNases into the CSF, more evident for non-pegylated formulations, was detected
when the ASNases were administered at high dose.
PMID- 28424965
TI - Assessment of drug-drug interaction potential between ceritinib and proton pump
inhibitors in healthy subjects and in patients with ALK-positive non-small cell
lung cancer.
AB - PURPOSE: The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK)
and efficacy of ceritinib was evaluated. METHODS: A healthy subject drug-drug
interaction (DDI) study was conducted to assess the effect of esomeprazole on the
PK of a single 750 mg dose of ceritinib. To further investigate the impact of
PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two
subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state
trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant
use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2
evaluated ceritinib single-dose and steady-state AUC0-24h and C max by
concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage
similar to that used in the healthy subject study. RESULTS: In the healthy
subject study, co-administration of a single 750 mg dose of ceritinib with
esomeprazole 40 mg for 6 days decreased ceritinib AUC0-infinity by 76% and C max
by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss
and ORR regardless of concomitant PPI usage. Based on analysis 2, co
administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients
suggested less effect on ceritinib exposure than that observed in healthy
subjects as AUC0-24h decreased by 30% and C max decreased by 25%. No clinically
meaningful effect on steady-state exposure was observed after daily dosing.
CONCLUSIONS: Long-term administration of ceritinib with PPIs does not adversely
affect the PK and efficacy of ceritinib in ALK-positive cancer patients.
PMID- 28424966
TI - Transcriptomic analysis of molecular responses in Malus domestica 'M26' roots
affected by apple replant disease.
AB - KEY MESSAGE: Gene expression studies in roots of apple replant disease affected
plants suggested defense reactions towards biotic stress to occur which did not
lead to adequate responses to the biotic stressors. Apple replant disease (ARD)
leads to growth inhibition and fruit yield reduction in replanted populations and
results in economic losses for tree nurseries and fruit producers. The etiology
is not well understood on a molecular level and causal agents show a great
diversity indicating that no definitive cause, which applies to the majority of
cases, has been found out yet. Hence, it is pivotal to gain a better
understanding of the molecular and physiological reactions of the plant when
affected by ARD and later to overcome the disease, for example by developing
tolerant rootstocks. For the first time, gene expression was investigated in
roots of ARD affected plants employing massive analysis of cDNA ends (MACE) and
RT-qPCR. In reaction to ARD, genes in secondary metabolite production as well as
plant defense, regulatory and signaling genes were upregulated whereas for
several genes involved in primary metabolism lower expression was detected. For
internal verification of MACE data, candidate genes were tested via RT-qPCR and a
strong positive correlation between both datasets was observed. Comparison of
apple 'M26' roots cultivated in ARD soil or gamma-irradiated ARD soil suggests
that typical defense reactions towards biotic stress take place in ARD affected
plants but they did not allow responding to the biotic stressors attack
adequately, leading to the observed growth depressions in ARD variants.
PMID- 28424967
TI - Disparities of Selected Metal Levels in the Blood and Scalp Hair of Ischemia
Heart Disease Patients and Healthy Subjects.
AB - Imbalances in the concentrations of trace metals have become an increasingly
recognized source of infirmity worldwide particularly in the development of
ischemia heart disease (IHD). Present study is intended to analyze the
concentrations of Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Pb, Sr, and Zn in
the blood and scalp hair of the patients and counterpart controls by flame atomic
absorption spectrometry after wet-acid digestion. On the average, Cd, Co, Cr, Fe,
K, Li, Mn, Na, and Pb revealed significantly elevated concentrations in the blood
of the patients compared with the controls (p < 0.05), whereas mean levels of Ca,
Cd, Fe, K, Li, Pb, and Sr in the scalp hair were significantly higher in the
patients than the controls (p < 0.05). Most of the metals exhibited noticeable
disparities in their concentrations based on gender, abode, dietary/smoking
habits, and occupations of both donor groups. The correlation study and
multivariate statistical analyses revealed some significantly divergent
associations and apportionment of the metals in both donor groups. Overall,
comparative variations of the metal contents in blood/scalp hair of the patients
were significantly different than the controls; thus, evaluation of trace metals
status may be indicative of pathological disorders, such as IHD.
PMID- 28424968
TI - Visualization of reticulophagy in living cells using an endoplasmic reticulum
targeted p62 mutant.
AB - Reticulophagy is a type of selective autophagy in which protein aggregate
containing and/or damaged endoplasmic reticulum (ER) fragments are engulfed for
lysosomal degradation, which is important for ER homeostasis. Several chemical
drugs and mutant proteins that promote protein aggregate formation within the ER
lumen can efficiently induce reticulophagy in mammalian cells. However, the exact
mechanism and cellular localization of reticulophagy remain unclear. In this
report, we took advantage of the self-oligomerization property of p62/SQSTM1, an
adaptor for selective autophagy, and developed a novel reticulophagy system based
on an ER-targeted p62 mutant to investigate the process of reticulophagy in
living cells. LC3 conversion analysis via western blot suggested that p62 mutant
aggregate-induced ER stress triggered a cellular autophagic response. Confocal
imaging showed that in cells with moderate aggregation conditions, the aggregates
of ER-targeted p62 mutants were efficiently sequestered by autophagosomes, which
was characterized by colocalization with the autophagosome precursor marker
ATG16L1, the omegasome marker DFCP1, and the late autophagosomal marker LC3/GATE
16. Moreover, time-lapse imaging data demonstrated that the LC3- or DFCP1
positive protein aggregates are tightly associated with the reticular structures
of the ER, thereby suggesting that reticulophagy occurs at the ER and that
omegasomes may be involved in this process.
PMID- 28424969
TI - Values and limitations of the comparing thyroid radiofrequency and microwave
ablation using propensity score.
PMID- 28424970
TI - Neighborhood Environments and Sexual Risk Behaviors for HIV Infection Among U.S.
Women: A Systematic Review.
AB - Empirical evidence indicates that aspects of the neighborhood environment may
affect HIV prevention efforts. Therefore, the neighborhood environment should be
considered when implementing prevention interventions. However, much of the
empirical evidence is derived from studies conducted among drug users, men, or
adolescents. Such evidence may not be as applicable to adult women whose primary
risk for HIV infection is via heterosexual sexual behavior. Therefore, a
systematic review examining the relationship between neighborhood environments
and HIV sexual risk behaviors among adult U.S. women was conducted. Three
databases were searched for articles published in English in peer-reviewed
journals between 1/1/1980 and 12/31/2016 meeting relevant criteria. Seven
articles identified from the three databases or additional hand searches met
inclusion criteria and were summarized. Findings were mixed with several studies
indicating associations between neighborhood environments and HIV sexual risk
behaviors. However, all summarized studies were cross-sectional. Longitudinal
studies conducted among women are needed.
PMID- 28424971
TI - High Frequency of Illegal Drug Use Influences Condom Use Among Female Transgender
Sex Workers in Argentina: Impact on HIV and Syphilis Infections.
AB - The high prevalence of HIV and syphilis found among female transgender sex
workers (FTSWs) in Argentina calls for the study of factors leading to negative
health consequences. Given the particular characteristics observed in this
population (high marginalization, school dropout, and low adherence to healthcare
services), we explored the association of several socio-demographic
characteristics with syphilis and HIV infections, and the determinants of condom
use. This study revealed that FTSWs from Argentina were exposed to several risk
factors decreasing thus their ability to negotiate condom use and leading to
increased risk for transmission of HIV and other sexually transmitted infections
(STIs). Strategies to reduce HIV and syphilis in this population should consider
interventions aimed at decreasing violence and substance use which appear to be
the most important determinants. Results of this study will contribute to the
global information among FTSWs.
PMID- 28424972
TI - Biosimilars in the United States: Emerging Issues in Litigation.
AB - Many first-generation biologics will lose their patent protection by 2020. The
biosimilars market is not only attractive but also competitive and tough. The
United States (US) is the world's largest pharmaceutical market and is critical
to the success of most drugs. However, unclear regulatory requirements and
confusing patent resolution procedures create hurdles to market entry of
biosimilars. Trade secret exposure and scant exclusivity and adoption also limit
the market access of biosimilars. Both biologics and biosimilar developers should
closely follow the regulatory and litigation landscape to successfully navigate
through the challenges. Focusing on the US landscape, this article provides a
brief review of the regulatory framework for biosimilar products, market
exclusivities, and patent issues under the Biologics Price Control and Innovation
Act (BPCIA), analyzes emerging issues in the biosimilar litigation landscape, and
provides recommendations for companies entering the biosimilars market.
PMID- 28424973
TI - PCSK9 Inhibitors in Hyperlipidemia: Current Status and Clinical Outlook.
AB - The clinical reality of residual risk despite statin (HMG-CoA reductase
inhibitor) therapy and emergence of statin intolerance support the need to
develop additional lipid-lowering strategies. Proprotein convertase subtilisin
kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and
clinical studies that have revealed its pivotal role in the regulation of
cholesterol homeostasis. Monoclonal antibodies have been developed targeting
PCSK9, which have been demonstrated to produce profound low-density lipoprotein
cholesterol (LDL-C) lowering when provided as monotherapy or in combination with
statins. With the reports that the PCSK9 inhibitor evolocumab has a favorable
impact on both plaque progression and cardiovascular outcomes, these findings
begin to translate the benefits of PCSK9 inhibition from lipids to the vessel
wall and ultimately to clinical outcomes. The clinical implications for the use
of these agents are reviewed in this article.
PMID- 28424974
TI - Transposable elements in the Anopheles funestus transcriptome.
AB - Transposable elements (TEs) are present in most of the eukaryotic genomes and
their impact on genome evolution is increasingly recognized. Although there is
extensive information on the TEs present in several eukaryotic genomes, less is
known about the expression of these elements at the transcriptome level. Here we
present a detailed analysis regarding the expression of TEs in Anopheles
funestus, the second most important vector of human malaria in Africa. Several
transcriptionally active TE families belonging both to Class I and II were
identified and characterized. Interestingly, we have identified a full-length
putative active element (including the presence of full length TIRs in the
genomic sequence) belonging to the hAT superfamily, which presents active members
in other insect genomes. This work contributes to a comprehensive understanding
of the landscape of transposable elements in A. funestus transcriptome. Our
results reveal that TEs are abundant and diverse in the mosquito and that most of
the TE families found in the genome are represented in the mosquito
transcriptome, a fact that could indicate activity of these elements.The vast
diversity of TEs expressed in A. funestus suggests that there is ongoing
amplification of several families in this organism.
PMID- 28424975
TI - ETV-2 activated proliferation of endothelial cells and attenuated acute hindlimb
ischemia in mice.
AB - Ischemia is the reduction of blood flow to tissues by injury of blood vessels.
Depending on the sites of tissues and grade of ischemia, ischemia can cause many
serious complications. This study aimed to evaluate the effects of the E-twenty
six (ETS) factor Ets variant 2 (ETV2) gene expression in angiogenesis and the
effect of ETV2 gene therapy in a mouse model of hindlimb ischemia. The role of
ETV2 on endothelial cell proliferation was evaluated in vitro. Knockdown of ETV2
expression was done using short hairpin RNA (shRNA) lentiviral viral particles.
The ETV2 viral vector was injected into the skeletal muscles at the ligated and
burned sites of the hindlimb and evaluated for its efficacy as a gene therapy
modality for ischemia. Vascular regeneration in mice was indirectly evaluated by
changes in mouse survival, necrotic grades of the leg, normal blood oxygen
saturation level (SpO2), and blood flow by trypan blue injection assay.
Preliminary data showed that ETV2 expression played a role in angiogenesis of
endothelial cells. ETV2 overexpression could trigger and stimulate proliferation
of skeletal endothelial cells. In vivo knockdown of ETV2 expression inhibited the
auto-recovery of ischemic hindlimb, while overexpression of ETV2 helped to rescue
leg loss and reduce necrosis, significantly improving angiogenesis in hindlimb
ischemia. Our findings demonstrate that ETV2 gene therapy is a potentially
effective modality for vascular regeneration.
PMID- 28424976
TI - The Involvement of NR2B and tau Protein in MG132-Induced CREB Dephosphorylation.
AB - Transcription factor cAMP response element-binding protein (CREB) plays a
critical role in memory formation. Ubiquitin-proteasome system-dependent protein
degradation affects the upstream signaling pathways which regulate CREB activity.
However, the molecular mechanisms of proteasome inhibition on reductive CREB
activity are still unclear. The current study demonstrated that MG132-inhibited
proteasome activity resulted in a dose dependence of CREB dephosphorylation at
Ser133 as well as decreased phosphorylation of N-methyl-D-aspartate (NMDA)
receptor subunit NR2B (Tyr1472) and its tyrosine protein kinase Fyn (Tyr416).
These dephosphorylations are probably caused by disturbance of expression and
post-translational modifications of tau protein since tau siRNA decreased the
activity of Fyn, NR2B, and CREB. To further confirm this perspective, HEK293
cells stably expressing human tau441 protein were treated with MG132 and
dephosphorylations of CREB and NR2B were observed. The current research provides
an alternative pathway, tau/Fyn/NR2B signaling, regulating CREB activity.
PMID- 28424977
TI - Restless legs syndrome and tension-type headache: a population-based study.
AB - BACKGROUND: Recent studies have shown a significant association between restless
legs syndrome (RLS) and primary headache disorders. Nevertheless, information
regarding the association between tension-type headache (TTH) and RLS is limited.
This study aimed to investigate the association between RLS and TTH in a
population-based sample. METHODS: We selected a stratified random population
sample of Koreans aged 19-69 years and assessed them using a semi-structured
interview designed to identify RLS, headache type, and clinical characteristics
of TTH. We determined the prevalence and clinical impact of RLS in participants
with TTH. RESULTS: Of the 2695 participants, 570 (21.2%) and 142 (5.3%) were
classified as having TTH and RLS, respectively. Among the 570 individuals with
TTH, 113 (19.8%) also met the criteria for probable migraine (PM). The prevalence
of RLS was significantly higher among individuals with TTH than among those with
non-headache (6.0% vs 3.6%, p = 0.018). The prevalence of RLS was significantly
higher in subjects with TTH who fulfilled PM criteria than in those with non
headache participants (8.0% vs. 3.6%, p = 0.018). However, RLS prevalence in
individuals with TTH who did not fulfil PM criteria did not differ from that of
participants with non-headache (5.5% vs. 3.6%, p = 0.063). TTH participants with
RLS had higher visual analogue scale scores for headache intensity (5.1 +/- 2.0
vs. 4.3 +/- 1.8, p = 0.038), and higher prevalence of anxiety (20.6% vs. 8.8%, p
= 0.022) and depression (14.7% vs. 3.5%, p = 0.002) than TTH participants without
RLS. Multivariable analyses revealed that headache aggravation by movement (odds
ratio [OR] = 2.4, 95% confidence interval [CI] = 1.1-5.2) and depression (OR =
3.5, 95% CI = 1.1-11.4) were significant indicators of RLS among individuals with
TTH. CONCLUSIONS: The prevalence of RLS was higher among individuals with TTH
than among those with non-headache. Some clinical presentations varied in
accordance with the presence of RLS among participants with TTH.
PMID- 28424978
TI - The Physicochemical Investigation of 17beta-Estradiol Crystalline Prepared by In
Situ pH-Dependent Solubility Technique with Polyvinylpyrrolidone.
AB - Micro-particles of 17beta-estradiol (ED) were prepared with polyvinylpyrrolidone
(PVP) by in situ pH-dependent solubility technique. Products were characterized
using multiple instruments, and molecular interactions between ED and PVP were
explored. Powder X-ray diffraction and thermal analysis revealed crystalline ED
in the micro-particles is hemihydrated. PVP was also present in the micro
particles. Laser particle size analysis and scanning electron microscopy revealed
thin slice morphology, which might have resulted from the influence of PVP.
Moreover, the results of contact angle, specific surface area, and dynamic vapor
sorption showed that the surface properties of products were improved. These
physicochemical properties of the micro-particles resulted in an obvious
improvement in dissolution rate. Fourier transform infrared spectroscopy and 1H
nuclear magnetic resonance revealed hydrogen bonding between ED and PVP. A method
was established for the preparation of micro-particles through the addition of
PVP during the reaction process.
PMID- 28424979
TI - Studies on Core-Shell Nanocapsules of Felodipine: In Vitro-In Vivo Evaluations.
AB - The present study aimed for in vitro-in vivo-in silico simulation studies of
experimentally designed (32-factorial) Capmul PG-8-cored, Eudragit RSPO-Lutrol F
127 nanocapsules to ferry felodipine using GastroPlusTM. The in silico parameter
sensitivity analysis for pharmacokinetic parameters was initially assessed to
justify the preparation of felodipine-loaded nanocapsules (FLNs) with enhanced
solubility to overcome the bioavailability issues of felodipine. The overall
integrated desirability ranged between 0.8187 and 0.9488 for three optimized FLNs
when analyzed for mean particle size, zeta potential, encapsulation efficiency,
and in vitro dissolution parameters. The morphological evaluation (SEM, TEM, and
AFM) demonstrated spherical nanoparticles (200-300 nm). Validated LC-MS/MS
analysis demonstrated enhanced relative bioavailability (13.37-fold) of optimized
FLN as compared to suspension. The simulated regional absorption of the FLN
presented significant absorption from the cecum (26.3%) and ascending colon
(20.1%) with overall absorption of 67.4% from the GIT tract. Furthermore, in
vitro-in vivo correlation demonstrated the Wagner-Nelson method as the preferred
model as compared to mechanistic and numerical deconvolution on the basis of
least mean absolute prediction error, least standard error of prediction, least
mean absolute error, and maximum correlation coefficient (r 2 = 0.920). The study
demonstrated enhanced oral absorption of felodipine-loaded nanocapsules, and
GastroPlusTM was found to be an efficient simulation tool for in vitro-in vivo-in
silico simulations.
PMID- 28424980
TI - Capsule Commentary on Patel el al., Using Active Choice Within the Electronic
Health Record to Increase Influenza Vaccination Rates.
PMID- 28424981
TI - Capsule Commentary on Pololi et al., Assessing the Culture of Residency Using the
C-Change Resident Survey: Validity Evidence in 34 US Residency Programs.
PMID- 28424982
TI - Finding Common Ground: Educating General Psychiatry Residents About Forensic
Psychiatry.
PMID- 28424983
TI - The Effect of Gastrostomy Placement on Gastric Function in Children: a
Prospective Cohort Study.
AB - BACKGROUND: A gastrostomy placement is frequently performed in pediatric patients
who require long-term enteral tube feeding. Unfortunately, postoperative
complications such as leakage, feeding intolerance, and gastroesophageal reflux
frequently occur. These complications may be due to postoperative gastric
dysmotility. Our aim was to evaluate the effect of gastrostomy placement on
gastric emptying in children. METHODS: A prospective study was performed
including 50 children undergoing laparoscopic gastrostomy. Before and 3 months
after gastrostomy, assessment was performed using the 13C-octanoic acid breath
test, 24-h pH monitoring, and reflux symptom questionnaires. RESULTS: Gastric
half-emptying time significantly increased from the 57th to the 79th percentile
(p < 0.001) after gastrostomy (p < 0.001). Fifty percent of patients with normal
preoperative gastric emptying develop delayed gastric emptying (DGE, P > 95)
after gastrostomy (p = 0.01). Most patients (>=75%) with leakage and/or feeding
intolerance after gastrostomy had DGE after operation. A decrease in gastric
emptying was associated with an increase in esophageal acid exposure time (r =
0.375, p < 0.001). CONCLUSION: Gastrostomy placement in children causes a
significant delay in gastric emptying. Postoperative DGE was associated with
gastroesophageal reflux and was found in most patients with postoperative leakage
and feeding intolerance. These negative physiologic effects should be taken into
account when considering gastrostomy placement in children.
PMID- 28424984
TI - Management of Ingested Hijab-Pin.
AB - BACKGROUND AND STUDY AIMS: Accidental swallowing of hijab (or turban) pin was
reported mainly among adolescent girls. Current guidelines indicate emergent
intervention endoscopy in case a long sharp object is found in the
gastrointestinal tract. The aims of the current study are to present the results
of an observational approach and to assess the need for intervention. PATIENTS
AND METHODS: A retrospective cohort study was conducted including all 5-18-year
old patients who presented with hijab-pin ingestion between 2003 and 2014. The
need for intervention was assessed using both univariable and multivariable
statistical analyses. RESULTS: Two hundred three cases of hijab-pin ingestion
were documented. In the majority of cases, the pin was observed in the stomach
(137/203, 67.4%) upon arrival. Most pins that were located at the upper
gastrointestinal tract (proximal to the ligament of Treitz) ejected spontaneously
(120/169, 71%, Pv = 0.005). The absence of pin progression in an X-ray performed
12 h following presentation was significantly more frequent in the intervention
group (46/51, 90%, Pv = 0.001). CONCLUSIONS: In most cases, the outcome is
spontaneous ejection from the digestive tract. However, if needle location
remains unchanged on two consecutive X-rays, an endoscopic intervention is
recommended.
PMID- 28424985
TI - Postoperative Complications and Functional Outcome after Esophageal Atresia
Repair: Results from Longitudinal Single-Center Follow-Up.
AB - BACKGROUND: Esophageal atresia (EA) and tracheoesophageal fistula (TEF) represent
major therapeutic challenges, frequently associated with serious morbidities
following surgical repair. The aim of this longitudinal study was to assess
temporal changes in morbidity and mortality of patients with EA/TEF treated in a
tertiary-level center, focusing on postoperative complications and their impact
on long-term gastroesophageal function. METHODS: One hundred nine consecutive
patients with EA/TEF born between 1975 and 2011 were followed for a median of 9.6
years (range, 3-27 years). Comparative statistics were used to evaluate temporal
changes between an early (1975-1989) and late (1990-2011) study period. RESULTS:
Gross types of EA were A (n = 6), B (n = 5), C (n = 89), D (n = 7), and E (n =
2). Seventy (64.2%) patients had coexisting anomalies, 13 (11.9%) of whom died
before EA correction was completed. In the remaining 96 infants, surgical repair
was primary (n = 66) or delayed (n = 25) anastomosis, closure of TEF in EA type E
(n = 2), and esophageal replacement with colon interposition (n=2) or gastric
transposition (n=1). Long-gap EA was diagnosed in 23 (24.0%) cases. Postoperative
mortality was 4/96 (4.2%). Overall survival increased significantly between the
two study periods (42/55 vs. 50/54; P = 0.03). Sixty-nine (71.9%) patients
presented postoperatively with anastomotic strictures requiring a median of 3
(range, 1-15) dilatations. Revisional surgery was required for anastomotic
leakage (n = 5), recurrent TEF with (n = 1) or without (n=9) anastomotic
stricture, undetected proximal TEF (n = 4), and refractory anastomotic strictures
with (n = 1) or without (n = 2) fistula. Normal dietary intake was achieved in 89
(96.7%) patients, while 3 (3.3%) remained dependent on gastrostomy feedings.
Manometry showed esophageal dysmotility in 78 (84.8%) infants at 1 year of age,
increasing to 100% at 10-year follow-up. Fifty-six (60.9%) patients suffered from
dysphagia with need for endoscopic foreign body removal in 12 (13.0%) cases. Anti
reflux medication was required in 43 (46.7%) children and 30 (32.6%) underwent
fundoplication. The rate of gastroesophageal reflux increased significantly
between the two study periods (29/42 vs. 44/50; P = 0.04). Twenty-two (23.9%)
cases of endoscopic esophagitis and one Barrett's esophagus were identified.
CONCLUSIONS: Postoperative complications after EA/TEF repair are common and
should be expertly managed to reduce the risk of long-term morbidity. Regular
multidisciplinary surveillance with transitional care into adulthood is
recommended in all patients with EA/TEF.
PMID- 28424986
TI - Extremely Giant Liver Hemangioma (50 cm) with Kasabach-Merritt Syndrome.
AB - A 33-year-old male has been found with a giant liver hemangioma of initial size
29 cm for 5 years. He received arterial embolization twice in order to shrink the
tumor; however, no effect was obtained. The tumor had rapidly grown to 50 cm and
caused abnormalities in the hematological and coagulative systems. Preoperative
computed tomography revealed that the right hepatic vein, right hepatic artery,
and right portal vein were not involved by the hemangioma. Resection of the giant
liver hemangioma was successfully performed after intraoperative intentional
bloodletting with concurrent blood salvage. All hematological and coagulative
abnormalities had returned to normal after the procedure.
PMID- 28424987
TI - Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for
Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System.
AB - INTRODUCTION: The role of routine lymphadenectomy for intrahepatic
cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition
recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal
staging. We sought to define outcome and risk of death among patients who were
staged with >=6 HLNs versus <6 HLNs. MATERIALS AND METHODS: Patients undergoing
hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary
centers were identified. RESULTS: Among 1154 patients undergoing hepatectomy for
ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients
had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN).
Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did
not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was
associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged
according the AJCC eighth edition staging system, N1 patients had a 3-fold
increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001).
CONCLUSION: Only one fourth of patients undergoing hepatectomy for ICC had
adequate nodal staging according to the AJCC eighth edition. While the six HLN
cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN
was associated with long-term survival of N1 patients.
PMID- 28424989
TI - T-lymphocyte-derived enkephalins reduce Th1/Th17 colitis and associated pain in
mice.
AB - BACKGROUND: Endogenous opioids, including enkephalins, are fundamental regulators
of pain. In inflammatory conditions, the local release of opioids by leukocytes
at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia.
Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins
released by colitogenic CD4+ T lymphocytes relieve inflammation-induced visceral
pain. The present study aims to investigate whether mucosal T-cell-derived
enkephalins also exhibit a potent anti-inflammatory activity as described for
exogenous opioid drugs in Th1/Th17-associated colitis. METHODS: The anti
inflammatory effects of endogenous opioids were investigated in both Th1/Th17
associated (transfer of CD4+CD45RBhigh T lymphocytes) and Th2-associated
(oxazolone) colitis models in mice. Inflammation-induced colonic damage and CD4+
T cell subsets were compared in mice treated or not treated with naloxone
methiodide, a peripheral antagonist of opioid receptors. The anti-inflammatory
activity of T-cell-derived enkephalins was further estimated by comparison of
colitis severity in immunodeficient mice into which naive CD4+CD45RBhigh T
lymphocytes originating from wild-type or enkephalin-knockout mice had been
transferred. RESULTS: Peripheral opioid receptor blockade increases the severity
of Th1/Th17-induced colitis and attenuates Th2 oxazolone colitis. The opposite
effects of naloxone methiodide treatment in these two models of intestinal
inflammation are dependent on the potency of endogenous opioids to promote a Th2
type immune response. Accordingly, the transfer of enkephalin-deficient
CD4+CD45RBhigh T lymphocytes into immunodeficient mice exacerbates inflammation
induced colonic injury. CONCLUSIONS: Endogenous opioids, including T-cell-derived
enkephalins, promote a Th2-type immune response, which, depending on the context,
may either attenuate (Th1/Th17-associated) or aggravate (Th2-associated)
intestinal inflammation.
PMID- 28424988
TI - Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis
proteins (IAPs).
AB - Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant
role in the control of programmed cell death (PCD). PCD is essential to maintain
healthy cell turnover within tissue but also to fight disease or infection.
Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression.
Therefore, it is unsurprising that cancer cells demonstrate significantly
elevated expression levels of IAPs, resulting in improved cell survival, enhanced
tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has
garnered substantial scientific interest and as resistance to anti-cancer agents
becomes more prevalent, targeting IAPs has become an increasingly attractive
strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies
and TRAIL therapy. Antagonism strategies to modulate the actions of XIAP, cIAP1/2
and survivin are the central focus of current research and this review highlights
advances within this field with particular emphasis upon the development and
specificity of second mitochondria-derived activator of caspase (SMAC) mimetics
(synthetic analogs of endogenously expressed inhibitors of IAPs SMAC/DIABLO).
While we highlight the potential of SMAC mimetics as effective single agent or
combinatory therapies to treat cancer we also discuss the likely clinical
implications of resistance to SMAC mimetic therapy, occasionally observed in
cancer cell lines.
PMID- 28424990
TI - Proteomic Analysis of the Hippocampus in Mouse Models of Trigeminal Neuralgia and
Inescapable Shock-Induced Depression.
AB - To investigate the behavioral and biomolecular similarity between neuralgia and
depression, a trigeminal neuralgia (TN) mouse model was established by
constriction of the infraorbital nerve (CION) to mimic clinical trigeminal
neuropathic pain. A mouse learned helplessness (LH) model was developed to
investigate inescapable foot-shock-induced psychiatric disorders like depression
in humans. Mass spectrometry was used to assess changes in the biomolecules and
signaling pathways in the hippocampus from TN or LH mice. TN mice developed not
only significant mechanical allodynia but also depressive-like behaviors (mainly
behavioral despair) at 2 weeks after CION, similar to LH mice. MS analysis
demonstrated common and distinctive protein changes in the hippocampus between
groups. Many protein function families (such as cell-to-cell signaling and
interaction, and cell assembly and organization,) and signaling pathways (e.g.,
the Huntington's disease pathway) were involved in chronic neuralgia and
depression. Together, these results demonstrated that the LH and TN models both
develop depressive-like behaviors, and revealed the involvement of many
psychiatric disorder-related biomolecules/pathways in the pathogenesis of TN and
LH.
PMID- 28424991
TI - Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root
Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and
Regulation by Paclitaxel.
AB - Voltage-gated sodium channels (Navs) play an important role in human pain
sensation. However, the expression and role of Nav subtypes in native human
sensory neurons are unclear. To address this issue, we obtained human dorsal root
ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed
Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of
total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse
DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1.7 (~18%).
To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary
cultures with paclitaxel (0.1-1 MUmol/L) for 24 h. Paclitaxel increased the
Nav1.7 but not Nav1.8 expression and also increased the transient Na+ currents
and action potential firing frequency in small-diameter (<50 MUm) hDRG neurons.
Thus, the hDRG provides a translational model in which to study "human pain in a
dish" and test new pain therapeutics.
PMID- 28424993
TI - Performing corneal crosslinking under local anaesthesia in patients with Down
syndrome.
AB - PURPOSE: To report on the ability to perform corneal crosslinking (CXL) under
local anaesthesia for the treatment of keratoconus in patients with Down
syndrome. METHODS: Nine eyes of seven patients with both keratoconus and Down
syndrome were scheduled for an epithelium-off CXL procedure under local
anaesthesia. Exclusion criteria were a corneal thickness under 400 um and the
presence of corneal scars. A standardized clinical decision tool was used to
estimate patient cooperation and the likelihood for a successful procedure under
local rather than general anaesthesia. RESULTS: In seven eyes, the CXL was
completed successfully. The treatment was aborted in two eyes due to insufficient
corneal thickness (<400 um) prior to ultraviolet-A irradiation, even after
employing hypoosmolar riboflavin. No adverse events occurred post-operatively,
except for one case of delayed epithelial healing (23 days). CONCLUSIONS: With a
proper patient selection, CXL under local anaesthesia can be achieved in patients
with Down syndrome.
PMID- 28424992
TI - Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to
punctate inner choroidopathy.
AB - PURPOSE: To assess the outcome of patients with choroidal neovascularization
(CNV) secondary to punctate inner choroidopathy (PIC) receiving intravitreal anti
VEGF (vascular endothelial growth factor) injections. METHODS: Sixteen eyes of 16
patients diagnosed with CNV secondary to PIC were retrospectively assessed.
RESULTS: Eleven women and five men with a mean age of 35 years (SD 11, range 16
56 years) received intravitreal anti-VEGF for PIC-related CNV. On average, 3.5
injections (SD 2.7, range 1-9) were given per eye. Thirteen eyes were treated
with bevacizumab, two eyes with ranibizumab and one eye received both substances.
The mean follow-up was 15 months (SD 11, range 6-40 months). BCVA improved in
eight eyes (mean Delta +2.8 lines), remained stable in four eyes and decreased in
four eyes (mean Delta -4.3 lines). CONCLUSIONS: CNV development is a frequent
complication of PIC. Intravitreal anti-VEGF therapy seems to be safe and
effective for PIC-related CNV.
PMID- 28424994
TI - Modulation of gastrointestinal motility beyond metoclopramide and domperidone :
Pharmacological and clinical evidence for phytotherapy in functional
gastrointestinal disorders.
AB - The prokinetic cisapride, an important therapeutic option in functional
gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due
to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP)
and domperidone in functional GI disorders (FGID) was restricted, consequently
leaving a therapeutic gap in clinical practice. A systematic review revealed that
the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent
to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in
randomized controlled clinical trials (RCTs) in functional dyspepsia and
irritable bowel syndrome, based on its multitarget effect on numerous etiological
factors. Due to an outstanding favorable safety profile, STW 5 allows an
effective and safe use in FGID without a limitation of the duration of the
treatment.
PMID- 28424995
TI - The emergence of vancomycin-resistant Staphylococcus aureus in an intensive care
unit in Kerman, Iran.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a global threat to public
health. This study is the first report of the emergence of vancomycin-resistant
MRSA in Kerman, Iran. During a period of 15 months, a total of 205 clinical
isolates of S. aureus were collected from three university hospitals affiliated
with the Kerman University of Medical Science, Kerman, Iran. Screening of
methicillin and vancomycin resistance was carried out by phenotypic methods. The
resistance and virulence genes of vancomycin-resistant isolates were detected by
polymerase chain reaction (PCR). Staphylococcal cassette chromosome mec (SCCmec)
and spa typing were used for molecular typing of vancomycin-resistant isolates.
Two S. aureus isolates were considered vancomycin-resistant by phenotypic and
genotypic methods. Both isolates showed a minimum inhibitory concentration (MIC)
>= 64 ug/ml and belonged to SCCmec III and spa type t030. Finding vancomycin
resistant S. aureus (VRSA) isolates represents a serious problem. More stringent
infection control policies are recommended to prevent transmission of such life
threatening isolates in the hospital setting.
PMID- 28424996
TI - [Quality assurance of pain care in Austria : Classification of management
facilities].
AB - In Austria there is no nationwide coverage of pain management, which meets even
approximately international criteria. At present there are about 30
interdisciplinary pain management offices and clinics providing care according to
a concept of the Austrian Pain Society (OSG), about 10 other outpatient pain
clinics are located in district and country hospitals. A few years ago, there
still were about 50 pain clinics. Yet closure of outpatient clinics and cost
cutting measures in the health sector jeopardize adequate pain relief for
patients with chronic pain conditions.Hence, the supply of care for approx. 1.8
mio. Austrians with chronic pain is not guaranteed due to lack of a comprehensive
demand planning of pain care facilities. Furthermore, existing structures such as
specialized clinics or emergency services in hospitals are primarily based on the
personal commitment of individuals. At present, the various centres for pain
management in Austria are run with very different operating times, so that for
74% of the chronic pain patients the desired requirements for outpatient pain
management are not met and about 50 full-time pain clinics are missing.Under the
patronage of the Austrian Pain Society, various national specialist societies
have defined the structure and quality criteria for pain management centres in
Austria, include, among others, proof of training, cooperation in
interdisciplinary teams or minimum number of new patients per year, depending on
the classification of the institution.This stepwise concept of care provision for
pain patients is intended as first step to help improve the care of pain patients
in Austria!
PMID- 28424997
TI - Changing Places, Changing Plates? A Binational Comparison of Barriers and
Facilitators to Healthful Eating Among Central American Communities.
AB - To understand the process by which immigrants adopt dietary practices, this study
offers a binational comparison of factors that predispose, enable, and reinforce
healthful eating in the sending and receiving countries. Data are from two
qualitative studies that examined barriers and facilitators to healthful eating
in El Salvador (four focus groups, n = 28 adults) and in the US (30 in-depth
interviews n = 15 mothers recently migrated from Central America). There was a
strong emphasis on hygiene and vitamin-content of foods among participants in El
Salvador. In both settings, participants perceived that their respective
community food environments (schools, food stores) exposed their families to
highly processed, unhealthful foods. In both settings, they described similar
struggles to encourage their families to eat foods healthfully (traditional, home
made foods). These results underscore the importance of acknowledging the
changing food environment in sending countries where people may already be
exposed to processed foods.
PMID- 28424998
TI - Correlates and Predictors of Mobility Limitation in Community-Dwelling Hispanic
Older Adults in the United States: A Systematic Review.
AB - This article presents a systematic review of the literature on
correlates/predictors of mobility limitation among community-dwelling U.S.
Hispanic older adults. A search of scientific databases (PubMed, CINAHL, and
PsycINFO) was conducted. After abstract and full text review, 20 epidemiologic
studies that met all eligibility criteria were included. The theoretical
framework of mobility was used to categorize factors related to mobility
limitation. The majority of the studies reviewed (n = 17) examined some aspect of
physical factors in relation to mobility limitation. Several factors emerged as
important influences on mobility outcomes: diabetes mellitus, stroke, obesity,
arthritis, and depression. None examined the influence of built environment. This
review suggests that multilevel factors can impact both mobility limitations and
disability among U.S. Hispanic older adults. However, the study findings were
inconsistent, with some studies showing significant relationships or effects and
others demonstrating no associations or mixed findings.
PMID- 28424999
TI - Alcohol use Exacerbates Acculturative Stress Among Recently Immigrated, Young
Adult Latinas.
AB - Associations between theorized sociocultural factors and acculturative stress
were examined among Latina immigrants (aged 18-23 years) during their initial
months in the US. Participants' quantity of alcohol use was hypothesized to be
linked with more acculturative stress. Using respondent-driven sampling, 530
Latinas who recently immigrated to Miami-Dade County, Florida, were recruited
from community activities, Latino health fairs, advertisements at community
agencies, and online postings. A path analysis revealed associations between
acculturative stress and more time in the US and greater commitment to ethnic
identity. Marianismo gender role beliefs differentially related with
acculturative stress. Quantity of alcohol use moderated the positive association
between time in US and acculturative stress, such that women in the US for less
time who drank more alcohol experienced higher levels of acculturative stress
than their peers. Findings suggest quantity of alcohol use may exacerbate
acculturative stress during some Latina young adult immigrants' initial months in
the US.
PMID- 28425000
TI - Medical Care, Screening and Regularization of Sub-Saharan Irregular Migrants
Affected by Hepatitis B in France and Italy.
AB - Both in France and in Italy hepatitis B is present mostly among the migrant
population coming from sub-Saharan Africa and mainly among those migrants having
a poor socio-economic background. This article is aimed at assaying the impact of
public policies adopted by France and Italy for migrants' health on the treatment
of migrants with HBV. The article is based on semi-structured interviews
conducted with 30 immigrant adults taken into care by two associations dealing
with medical, psychological and social issues of immigrants applying for a
residence permit, mainly asylum seekers. The results of this study bring to light
specific difficulties relating to national contexts, to the type of HBV (inactive
or active) and to the administrative situation of the migrants. In France
irregular migrants are screened in humanitarian associations. In Italy the
screening is done in public hospitals. In both countries, only migrants suffering
from chronic hepatitis B obtain a residence permit for medical reasons. More
migrants in Italy than in France abandon HBV treatment. This study describes how
specific national immigration and health policies impact in a different way the
therapeutic and social path of migrants suffering from hepatitis B. The analysis
provides useful material for the development of strategies to prevent and control
hepatitis B among the migrant population. It also shows how social determinants
affect migrants' health more than values or cultural factors do.
PMID- 28425002
TI - Beyond study participants: a framework for engaging patients in the selection or
development of clinical outcome assessments for evaluating the benefits of
treatment in medical product development.
AB - BACKGROUND: Patients are participating more actively in health care decision
making with regard to their health, as well as in the broader realm of assessing
the value of medical products and influencing decisions about their registration
and reimbursement. There is an increasing trend to include patients' perspectives
throughout the stages of medical product development by broadening the
traditional study-participant role to that of an active partner throughout the
process. Including patients in the selection and development of clinical outcome
assessments (COAs) to evaluate the benefit of treatment is particularly
important. Still, despite widespread enthusiasm, there is substantial uncertainty
regarding how and when to engage patients in this process. PURPOSE: This
manuscript proposes a methodological framework for engaging patients at varying
levels in the selection and development of COAs for medical product development.
FRAMEWORK: The framework builds on the Food and Drug Administration's roadmap for
patient-focused COA. Methods for engaging patients across each stage in this
roadmap are summarized by levels of engagement. Opportunities and examples of
patient engagement (PE) in the selection and/or development of COAs are
summarized, together with best practices and practical considerations.
CONCLUSION: This paper offers a framework for understanding, planning, and
implementing methods to advance PE in the selection and/or development of COAs
for evaluating the benefit of medical products. The intent is to further this
important discussion and enhance the process and outcome of PE in this context.
PMID- 28425003
TI - Validation of the Persian version of the Daily Spiritual Experiences Scale (DSES)
in Pregnant Women: A Proper Tool to Assess Spirituality Related to Mental Health.
AB - Assessing spirituality in healthy pregnant women may lead to supportive
interventions that will improve their care. A psychometrically valid measure such
as the Daily Spiritual Experiences Scale (DSES) may be helpful in this regard.
The current study sought to adapt a Persian version of DSES for use in pregnancy.
A total of 377 pregnant women were recruited from three general hospitals located
in Tehran, Iran. Administered scales were the DSES, Duke University Religion
Index, Santa Clara Strength of Religious Faith scale, and Depression Anxiety
Stress Scale, as well as demographic measures. Reliability of the DSES was tested
using Cronbach's alpha for internal consistency and the intraclass correlation
coefficient (ICC) for test-retest stability. Scale validity was assessed by
criterion-related tests, known-groups comparison, and exploratory factor
analysis. Participant's mean age was 27.7 (4.1), and most were nulliparous (70%).
The correlation coefficient between individual items on the scale and the total
score was greater than 0.30 in most cases. Cronbach's alpha for the scale was
0.90. The ICC for 2-week test-retest reliability was high (0.86). Relationships
between similar and dissimilar scales indicated acceptable convergent and
divergent validity. The factor structure of the scale indicated a single factor
that explained 59% of the variance. The DSES was found to be a reliable and valid
measure of spirituality in pregnant Iranian women. This scale may be used to
examine the relationship between spirituality and health outcomes, research that
may lead to supportive interventions in this population.
PMID- 28425004
TI - On the Inner Life of Physicians: Analysis of Family Medicine Residents' Written
Reflections.
AB - This qualitative study introduces the broad and inclusive concept of the "inner
life of physicians" and analyzes the written reflections (N = 756) of family
medicine residents (N = 33) during their residency as indicative of the
physicians' inner lives. Residents completed reflective entries without specific
prompts. Researchers describe unsolicited emergent categorical themes indicative
of a robust inner life of the physician. Nurturing physicians' inner life through
reflection allows physicians to recognize, identify, and respond to daily
emotional events. Reflections about the state of physicians' inner lives can
formulate and express fundamental human questions that concern: (a) troubling
human experiences (e.g., suffering, death, luck, destiny, and death); (b)
questions that surface in practicing their profession; (c) spiritually explicit
questions on their beliefs and practices. Physicians' inner lives can become a
"place" where physicians look for answers and explore options for dealing with
their human and professional challenges, thus enhancing the humanistic aspects of
medical practice.
PMID- 28425005
TI - Is Spiritual Well-Being Among Adolescents Associated with a Lower Level of
Bullying Behaviour? The Mediating Effect of Perceived Bullying Behaviour of
Peers.
AB - The aim of this study was to explore the association between spiritual well-being
and bullying among Slovak adolescents, and whether perceived bullying behaviour
of peers mediated this relationship. Data from the Health Behaviour in School
aged Children study conducted in 2014 in Slovakia were used. Data were obtained
from 9250 adolescents with a mean age of 13.48 years. The final sample consisted
of 762 adolescents aged 15 years old (52.2% boys). We used logistic regression
models and the Sobel test. Adolescents who reported a higher level of spiritual
well-being were at lower risk of reporting that some or more schoolmates bully
others or that they themselves bully others. These relationships were partially
mediated by perceived norms about the bullying behaviour of schoolmates.
Spiritual well-being was found to be negatively associated with bullying; in
addition, a mediating role of perceived bullying behaviour of peers in this
relationship was confirmed.
PMID- 28425006
TI - Religiosity, Gender, and Natural Disasters: A Qualitative Study of Disaster
Stricken Regions in Iran.
AB - While religiosity is emerging as one of the more important subjects in disaster
management, identifying gender differences in using religion as a coping method
has attracted very little attention. The aim of this study was to explore the
effects of religiosity on disaster-affected women and men in the setting of Iran.
A field-based investigation using a qualitative approach was carried out to
achieve the study's purpose. Data were collected using in-depth unstructured
interviews with 25 participants who had been damaged by recent disasters. Two
themes, negative and positive effects of religiosity, and five categories were
extracted from the data. Women may be influenced by religion more than men, and
thus, they can play key roles in strengthening the positive effects of
religiosity.
PMID- 28425007
TI - "No More Buzz": A Qualitative Study of the Current Response to HIV in the
Anglican Church in the Western Cape, South Africa.
AB - Using a triangulation design combining participant observation, survey results,
and interviews, this paper studies the current form of the response to HIV in the
local Anglican Church in the Western Cape, South Africa. The results show that
people are generally aware of HIV. The "buzz" around HIV has, however, subsided.
The local church does not directly engage HIV anymore, and HIV is more mentioned
than talked about. HIV stigma continues to pose a challenge. To work towards the
prevention of HIV, the local church needs to put HIV back on the agenda and
continue to speak about the virus.
PMID- 28425008
TI - Reversible Activation of Halophilic beta-lactamase from Methanol-Induced Inactive
Form: Contrast to Irreversible Inactivation of Non-Halophilic Counterpart.
AB - Effects of a water-miscible organic solvent, methanol, on the structure and
activity of halophilic beta-lactamase derived from Chromohalobacter sp.560
(HaBla), were investigated by means of circular dichroism (CD) measurement and
enzymatic activity determination. Beta-lactamase activity was enhanced about 1.2
fold in the presence of 10-20% methanol. CD measurement of HaBla revealed
different structures depending on the methanol concentration: native-like active
form (Form I) in 10-20% methanol and methanol-induced inactive form at higher
concentration (Form II in 40-60% and Form III in 75-80% methanol). Incubation of
HaBla with 40% methanol led to the complete loss of activity within ~80 min
accompanied by the formation of Form II, whose activity was recovered promptly up
to ~80% of full activity upon dilution of the methanol concentration to 10%. In
addition, when the protein concentration was sufficiently high (e.g., 0.7 mg/ml),
HaBla activity of Form III in 75% methanol could be recovered in the same way
(with slightly slower recovery rate), upon dilution of the methanol
concentration. In contrast, non-halophilic beta-lactamase from Escherichia coli
K12 strain MG1655 (EcBla) was irreversibly denatured in the presence of 40%
methanol. HaBla showed remarkable ability to renature from the methanol-induced
inactive states.
PMID- 28425009
TI - The Molecular Genetic Expression as a Novel Biomarker in the Evaluation and
Monitoring of Patients With Osteosarcoma-Subtype Bone Cancer Disease.
AB - One of the leading causes of death among patients with malignancies is
represented by bone cancer. According to current studies, the leading cause of
death among these patients is represented by late diagnosis, poor response to
therapy, and the lack of accuracy in terms of clinical evaluation. In this
regard, there have been developed a series of methods of diagnosis and
evaluation, the most investigated being represented by miRNA expression. In this
updated work, we want to present a series of changes in the expression of miRNAs
in bone cancer. Moreover, we want to present the implications of miRNAs in
targeted therapy in such patients. Studies available in scientific databases such
as PubMed and Scopus were examined. The studies were searched using the keywords
"miRNAs expression", "bone cancer", "genetic therapy" and "genetic biomarkers."
For the evaluation and monitoring of bone cancer, the expression of miRNAs can be
successfully used due to increased specificity. Using miRNAs as gene therapy can
be also considered a therapeutic method of the future, mainly due to selective
and targeted response of the body.
PMID- 28425010
TI - A novel fibrinogen variant: dysfibrinogenemia associated with gammaAsp185Asn
substitution.
AB - To identify the pathogenesis of a Chinese woman diagnosed with dysfibrinogenemia.
A patient from Nanjing presented with a low plasma concentration of fibrinogen
and a normal level of antigen of fibrinogen. This abnormality was also detected
in her son. To detect whether the genetic mutation was responsible for the
dysfibrinogenemia, genomic DNA was extracted and amplified by polymerase chain
reaction, and DNA sequencing was performed on the purified PCR products.
Restriction fragment length polymorphism (RFLP), molecular modeling and
homologous sequences alignment were performed. Two heterozygous missense
variants, AalphaArg16His and gammaAsp185Asn, were discovered in the proband. Only
the former was detected in her son. AalphaArg16His had been reported by other
teams, and gammaAsp185Asn was identified first in our study as a novel variant.
RFLP was performed and indicated that the novel failed to be found in normal
subjects. Furthermore, it was suggested to be responsible for dysfibrinogenemia
depending on the molecular modeling and homologous sequence alignment. The
heterozygous AalphaArg16His and gammaAsp185Asn identified in the study probably
underlie the dysfibrinogenemia in this pedigree, with the latter being identified
for the first time.
PMID- 28425011
TI - Pregnancy-related myocardial infarction.
AB - INTRODUCTION: The risk of acute myocardial infarction in young women is low, but
increases during pregnancy due to the physiological changes in pregnancy,
including hypercoagulability. Ischaemic heart disease during pregnancy is not
only associated with increased maternal morbidity and mortality, but also with
high neonatal complications. Advancing maternal age and other risk factors for
cardiovascular diseases may further increase the risk of ischaemic heart disease
in young women. METHODS: We searched the coronary angiography database of a Dutch
teaching hospital to identify women with acute myocardial infarction who
presented during pregnancy or postpartum between 2011 and 2013. RESULTS: We found
two cases. Both women were in their early thirties and both suffered from
myocardial infarction in the postpartum period. Acute myocardial infarction was
due to coronary stenotic occlusion in one patient and due to coronary artery
dissection in the other patient. Coronary artery dissection is a relatively
frequent cause of myocardial infarction during pregnancy. Both women were treated
by percutaneous coronary intervention and survived. CONCLUSION: Physicians should
be aware of the increased risk of myocardial infarction when encountering
pregnant or postpartum women presenting with chest pain.
PMID- 28425013
TI - Cannabinoids as Modulators of Cell Death: Clinical Applications and Future
Directions.
AB - Endocannabinoids are bioactive lipids that modulate various physiological
processes through G-protein-coupled receptors (CB1 and CB2) and other putative
targets. By sharing the activation of the same receptors, some phytocannabinoids
and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids.
In recent years, a growing interest has been dedicated to the study of
cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and
neuroprotective effects. In addition to these well-recognized effects, various
studies suggest that cannabinoids may affect cell survival, cell proliferation or
cell death. These observations indicate that cannabinoids may play an important
role in the regulation of cellular homeostasis and, thus, may contribute to
tissue remodelling and cancer treatment. For a long time, the study of
cannabinoid receptor signalling has been focused on the classical adenylyl
cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not
totally explain the wide array of biological responses to cannabinoids. In
addition, the diversity of receptors and signalling pathways that
endocannabinoids modulate offers an interesting opportunity for the development
of specific molecules to disturb selectively the endogenous system. Moreover,
emerging evidences suggest that cannabinoids ability to limit cell proliferation
and to induce tumour-selective cell death may offer a novel strategy in cancer
treatment. This review describes the main properties of cannabinoids in cell
death and attempts to clarify the different pathways triggered by these compounds
that may help to understand the complexity of respective molecular mechanisms and
explore the potential clinical benefit of cannabinoids use in cancer therapies.
PMID- 28425012
TI - A study of the damage of the intestinal mucosa barrier structure and function of
Ctenopharyngodon idella with Aeromonas hydrophila.
AB - The aim of this study is to explore the effect of Aeromonas hydrophila on the
intestinal mucosal barrier structure and intestinal permeability in grass carp
(Ctenopharyngodon idella). Histopathological examinations showed that A.
hydrophila induced severe intestinal lesions, including inflammatory cell
infiltration and intestinal villus fusion and swelling. Messenger RNA (mRNA)
expression of the inflammatory cytokines TNF-alpha, IL-1beta, IL-8, IL-10 and
MyD88 was significantly increased after infection with A. hydrophila. The
permeability of intestinal mucosa was determined using Evans blue (EB) and D
lactic acid. The results indicated that the levels of EB and serum D-lactic acid
were significantly increased after infection with A. hydrophila (p < 0.05). Our
results also indicated that the intestinal mucosal barrier injury induced by A.
hydrophila infection was closely associated with the expression of the tight
junction (TJ) protein zonula occludens-1 (ZO-1), occludin, claudin b and claudin
c as well as the activity of Na+, K+-ATPase and Ca2+, Mg2+-ATPase. Lower mRNA
levels of occludin and lower Na+, K+-ATPase and Ca2+, Mg2+-ATPase activity in the
intestines were observed after challenge. ZO-1 and claudin c were significantly
increased 24 h after infection with A. hydrophila. The most interesting finding
was that claudin b also significantly increased 24 h after challenge and then
decreased to lower levels at 72, 120 and 168 h post-infection compared to the PBS
treated control group. The results demonstrated that grass carp infection with A.
hydrophila induced intestinal inflammation and impaired the structure and
function of the intestinal mucosal barrier.
PMID- 28425014
TI - Clinicopathological and prognostic significance of Ki-67 immunohistochemical
expression of distant metastatic lesions in patients with metastatic breast
cancer.
AB - BACKGROUND: Surgical biopsy of metastatic lesions followed by pathological
confirmation for the investigation of biomarkers is occasionally proposed as an
effective strategy in the treatment of metastatic breast cancer. However, few
reports have examined Ki-67 immunohistochemical expression in distant metastatic
lesions of breast cancer patients. This study aimed to investigate the
clinicopathological significance of subtypes and Ki-67 immunohistochemical
expression in metastatic breast cancer lesions. METHODS: We retrospectively
studied surgical specimens of primary breast cancer tumors and their
corresponding metastatic lesions from patients (n = 68) who underwent surgery for
primary breast cancer tumors between December 1977 and March 2013. Tissue
microarrays were constructed using primary and metastatic lesions, and were
stained with antibodies against estrogen receptor, progesterone receptor, human
epidermal growth factor receptor 2, and Ki-67. We also examined the
clinicopathological characteristics and outcome measures of patients with
metastatic breast cancer using primary and paired metastatic lesions. RESULTS:
Compared with the primary lesions, there was no significant difference in
subtypes in the metastatic lesions according to metastatic sites. Metastatic
lesions of the brain, viscera, and bone exhibited slightly higher levels of Ki-67
immunohistochemical expression compared with primary lesions. A Cox proportional
hazards model using multivariate analysis demonstrated that high Ki-67
immunohistochemical expression in distant metastatic lesions was associated with
poorer overall survival outcomes after biopsy of recurrence lesion (hazard ratio
2.307; 95% confidence interval 1.207-4.407, P = 0.011). CONCLUSIONS: High Ki-67
immunohistochemical expression levels in distant metastatic lesions were
independently associated with poorer overall survival outcomes after biopsy of
recurrence lesion in breast cancer patients.
PMID- 28425015
TI - The New Classification of Seizures by the International League Against Epilepsy
2017.
AB - PURPOSE OF REVIEW: This review presents the newly developed International League
Against Epilepsy (ILAE) 2017 classification of seizure types. RECENT FINDINGS:
The fundamental distinction is between seizures that begin focally in one
hemisphere of the brain, generalized onset seizures that apparently originate in
both hemispheres, and seizures of unknown onset. Focal seizures optionally can be
subclassified according to whether awareness (a surrogate marker for
consciousness) is intact or impaired. The next level of classification for focal
seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms,
hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior
arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic.
Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic,
myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms)
and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The
classification allows new types of focal seizures and a few new generalized
seizures, and clarifies terms used to name seizures.
PMID- 28425016
TI - A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the
differentiation between non-significant and significant fibrosis in patients with
chronic hepatitis C.
AB - INTRODUCTION: A simple non-invasive score (Fibrofast, FIB-5) was developed using
five routine laboratory tests (ALT, AST, alkaline phosphatase, albumin and
platelets count) for the detection of significant hepatic fibrosis in patients
with chronic hepatitis C. The FIB-4 index is a non-invasive test for the
assessment of liver fibrosis, and a score of <=1.45 enables the correct
identification of patients who have non-significant (F0-1) from significant
fibrosis (F2-4), and could avoid liver biopsy. The aim of this study was to
compare the performance characteristics of FIB-5 and FIB-4 to differentiate
between non-significant and significant fibrosis. METHOD: A cross-sectional study
included 604 chronic HCV patients. All liver biopsies were scored using the
METAVIR system. Both FIB-5 and FIB-4 scores were measured and the performance
characteristics were calculated using the ROC curve. RESULTS: The performance
characteristics of FIB-5 at >=7.5 and FIB-4 at <=1.45 for the differentiation
between non-significant fibrosis and significant fibrosis were: specificity
94.4%, PPV 85.7%, and specificity 54.9%, PPV 55.7% respectively. CONCLUSION: FIB
5 score at the new cutoff is superior to FIB-4 index for the differentiation
between non-significant and significant fibrosis.
PMID- 28425017
TI - Spineless cactus associated with Tifton hay or sugarcane bagasse may replace corn
silage in sheep diets.
AB - The effect of the replacement of corn silage with spineless cactus associated
with Tifton 85 hay or sugarcane bagasse was evaluated on the performance, body
weight components and sheep meat quality. Twenty-one Santa Ines male sheep with
initial body weight of 22.9 +/- 2.9 kg were used. They were confined in
individual stalls for 74 days receiving the following diets: corn silage +
concentrate (CS); spineless cactus + Tifton 85 hay + concentrate (TH); spineless
cactus + sugarcane bagasse + concentrate (SB). After the feedlot period, the
animals were slaughtered and their body components were weighed and sampled. Data
were submitted to Tukey's test at 5% probability. The average daily gain (0.25 vs
0.14 kg), cold carcass weight (13.3 vs 13.7 kg), loin muscularity (0.6 vs 0.4 kg)
and liver weight (0.7 vs. 0.5 kg) were higher (P < 0.05) for the TH diet when
compared to that for the CS. The physical-chemical parameters of meat were not
influenced (P > 0.05) by the treatments and presented about 20.1% of crude
protein, 6.1% of crude fat and shear force of 2.0 kgf/cm2. In complete diets for
sheep, Tifton 85 hay associated with spineless cactus provides greater weight
gain, cold carcass muscularity and organ weight when compared to those for
animals fed with corn silage as exclusive roughage. Sugarcane bagasse associated
with spineless cactus may replace corn silage in complete diets for sheep.
PMID- 28425018
TI - Hepatocellular Carcinoma and Liver Transplantation: Changing Patterns and
Practices.
AB - OPINION STATEMENT: Benefits of liver transplantation (LT) for patients with
hepatocellular carcinoma (HCC) are well established. However, there is debate
regarding optimal and equitable selection of patients best served by LT,
particularly in the face of limited organ availability. Herein, we discuss topics
regarding LT selection criteria for patients with HCC. Recent change in UNOS
policy currently mandates a 6-month observation period prior to priority listing
and institutes a cap of 34 MELD exception points for patients with HCC.
Additionally, two further proposed changes to UNOS policy include (1) requiring
locoregional therapy for those with small (2-3 cm) unifocal HCC prior to applying
for exception points and (2) allowing downstaging in select patients with UNOS T3
lesions. These policies move beyond simply using tumor burden to using markers of
tumor biology for selecting patients who have the lowest risk of post-transplant
recurrence and best chance at long-term post-transplant survival. Given
increasing time on transplant waiting lists and shortage of donor grafts, LT
should be reserved for patients who may achieve significant benefit compared to
non-transplant therapies. Potential benefit to HCC patients must be weighed
against the harm from delaying or precluding LT for non-HCC patients on the
waiting list, particularly in regions with limited donor availability. The
relative benefit of LT in patients with small (<3 cm) HCC is likely limited;
surgical resection (in absence of portal hypertension) and local ablative therapy
(if portal hypertension present) are both efficacious and more cost-effective and
should likely be regarded as first line therapies for these patients. Salvage LT
can be considered as a rescue option for those with recurrent disease.
Downstaging for selected patients with UNOS T3 lesions may identify those with
good tumor biology and acceptable post-transplant outcomes; however, current
studies have had a wide variation in reported outcomes. While awaiting more data,
a standardized downstaging protocol including a priori inclusion criteria and a
mandatory waiting time prior to LT to observe tumor biology likely yields the
best outcomes.
PMID- 28425019
TI - Posttraumatic Stress Disorder Symptoms and Problematic Overeating Behaviors in
Young Men and Women.
AB - BACKGROUND: Posttraumatic stress disorder (PTSD) is a risk factor for obesity,
but the range of behaviors that contribute to this association are not known.
PURPOSE: The purpose of this study was to examine associations between self
reported PTSD symptoms in 2007, with and without comorbid depression symptoms,
and three problematic overeating behaviors in 2010, and to estimate the
associations of PTSD-related overeating behaviors with obesity. METHODS: Cross
sectional and longitudinal analyses included 7438 male (n = 2478) and female (n =
4960) participants from the Growing Up Today Study (mean age 22-29 years in
2010). Three eating behavior outcomes were assessed: binge eating (eating a large
amount of food in a short period of time with loss of control), top quartile of
coping-motivated eating (from the Motivations to Eat scale), and top quartile of
disinhibited eating (from the Three-Factor Eating Questionnaire). RESULTS: PTSD
symptoms were associated with two- to threefold increases in binge eating and top
quartile coping-motivated eating; having >=4 PTSD symptoms, relative to no PTSD
symptoms, was associated with covariate-adjusted RRs of 2.7 (95% CI 2.1, 3.4) for
binge eating, 2.1 (95% CI 1.9, 2.4) for the top quartile of coping-motivated
eating, and 1.5 (95% CI 1.3, 1.7) for the top quartile of disinhibited eating.
There was a trend toward PTSD symptoms in 2007 predicting new onset binge eating
in 2010. Having depression symptoms comorbid with PTSD symptoms further increased
risk of binge eating and coping-motivated eating. All eating behaviors were
associated with obesity. CONCLUSION: Clinicians treating patients with PTSD
should know of potential comorbid problematic eating behaviors that may
contribute to obesity.
PMID- 28425020
TI - Acoustic Properties of Cries in 12-Month Old Infants at High-Risk of Autism
Spectrum Disorder.
AB - There is preliminary evidence that infant siblings of children with Autism
Spectrum Disorder (ASD) have an atypical pattern of cry, characterized by higher
fundamental frequency and increased dysphonation. This prospective study
collected multiple cry samples of 12-month old siblings of children with ASD (n =
22, 'high-risk' group) and 12-month olds with no family history of ASD (n = 27,
'low risk' group). While there was no difference between groups in the
fundamental frequency or degree of phonation of the cry samples, the duration of
each cry unit was significantly shorter in the high-risk siblings (p < .05). The
six infant siblings who received a diagnosis of ASD at age two had amongst the
shortest recorded cry durations.
PMID- 28425021
TI - Is the Autism-Spectrum Quotient a Valid Measure of Traits Associated with the
Autism Spectrum? A Rasch Validation in Adults with and Without Autism Spectrum
Disorders.
AB - The Autism-Spectrum Quotient (AQ) is among the most widely used scales assessing
autistic traits in the general population. However, some aspects of the AQ are
questionable. To test its scale properties, the AQ was translated into Swedish,
and data were collected from 349 adults, 130 with autism spectrum disorder (ASD)
and 219 without ASD, and analysed with Rasch. Several scale properties of the AQ
were satisfactory but it did not meet the criterion of a unidimensional measure
of autistic traits. The Rasch analysis showed that the 50-item AQ could be
reduced to a 12-item subset with little loss of explanatory power, with the
potential to efficiently measure the degree to which adults with and without ASD
show autistic traits.
PMID- 28425022
TI - Social Motor Synchronization: Insights for Understanding Social Behavior in
Autism.
AB - Impairments in social interaction and communication are critical features of ASD
but the underlying processes are poorly understood. An under-explored area is the
social motor synchronization that happens when we coordinate our bodies with
others. Here, we explored the relationships between dynamical measures of social
motor synchronization and assessments of ASD traits. We found (a) spontaneous
social motor synchronization was associated with responding to joint attention,
cooperation, and theory of mind while intentional social motor synchronization
was associated with initiating joint attention and theory of mind; and (b) social
motor synchronization was associated with ASD severity but not fully explained by
motor problems. Findings suggest that objective measures of social motor
synchronization may provide insights into understanding ASD traits.
PMID- 28425023
TI - Challenges and Opportunities in Global Mental Health: a Research-to-Practice
Perspective.
AB - PURPOSE OF REVIEW: Globally, the majority of those who need mental health care
worldwide lack access to high-quality mental health services. Stigma, human
resource shortages, fragmented service delivery models, and lack of research
capacity for implementation and policy change contribute to the current mental
health treatment gap. In this review, we describe how health systems in low- and
middle-income countries (LMICs) are addressing the mental health gap and further
identify challenges and priority areas for future research. RECENT FINDINGS:
Common mental disorders are responsible for the largest proportion of the global
burden of disease; yet, there is sound evidence that these disorders, as well as
severe mental disorders, can be successfully treated using evidence-based
interventions delivered by trained lay health workers in low-resource community
or primary care settings. Stigma is a barrier to service uptake. Prevention,
though necessary to address the mental health gap, has not solidified as a
research or programmatic focus. Research-to-practice implementation studies are
required to inform policies and scale-up services. Four priority areas are
identified for focused attention to diminish the mental health treatment gap and
to improve access to high-quality mental health services globally: diminishing
pervasive stigma, building mental health system treatment and research capacity,
implementing prevention programs to decrease the incidence of mental disorders,
and establishing sustainable scale up of public health systems to improve access
to mental health treatment using evidence-based interventions.
PMID- 28425024
TI - Lesinurad: A Review in Hyperuricaemia of Gout.
AB - Lesinurad (Zurampic(r)) is an oral selective inhibitor of the URAT1 and OAT4 uric
acid (UA) transporters of the kidney, via which it inhibits UA reabsorption and
thus increases renal UA excretion and lowers serum UA (sUA) levels. Lesinurad 200
mg once daily is indicated for use in combination with a xanthine oxidase
inhibitor (XOI) to treat hyperuricaemia in adults with gout who have not achieved
target sUA levels with an XOI alone. Approval was based on three 12-month phase 3
trials that evaluated lesinurad in combination with allopurinol in adults with
gout inadequately responsive to allopurinol (CLEAR 1 and 2) and in combination
with febuxostat in adults with tophaceous gout (CRYSTAL). The target sUA level of
<6 mg/dL at 6 months (primary endpoint) was achieved by significantly more
lesinurad plus allopurinol than placebo plus allopurinol recipients in the CLEAR
trials. In CRYSTAL (which enrolled patients regardless of prior XOI experience,
and included 3 weeks of febuxostat before randomization), the proportion of
patients who achieved an sUA target of <5 mg/dL did not reach statistical
significance between lesinurad plus febuxostat and placebo plus febuxostat at 6
months (primary endpoint), although significantly favoured the lesinurad plus
febuxostat group at 12 months. Notably, the sUA target of <5 mg/dL at 6 months
was met with lesinurad plus febuxostat in the CRYSTAL subgroup that had
uncontrolled hyperuricaemia at baseline, despite having received febuxostat pre
randomization. Lesinurad plus XOI regimens were generally not associated with
improvements in flares and tophi in these trials, although clinical benefit
became more apparent in 12-month extension studies; the regimens were also
generally well tolerated. Thus, lesinurad, in combination with an XOI, is an
emerging option for the treatment of hyperuricaemia in adults with gout who have
not achieved target sUA levels with an XOI alone.
PMID- 28425025
TI - Light-induced formation of dimeric LHCII.
AB - It emerges from numerous experiments that LHCII, the major photosynthetic antenna
complex of plants, can appear not only in the trimeric or monomeric states but
also as a dimer. We address the problem whether the dimeric form of the complex
is just a simple intermediate element of the trimer-monomer transformation or if
it can also be a physiologically relevant molecular organization form? Dimers of
LHCII were analyzed with application of native electrophoresis, time-resolved
fluorescence spectroscopy, and fluorescence correlation spectroscopy. The results
reveal the appearance of two types of LHCII dimers: one formed by the
dissociation of one monomer from the trimeric structure and the other formed by
association of monomers into a distinctively different molecular organizational
form, characterized by a high rate of chlorophyll excitation quenching. The
hypothetical structure of such an energy quencher is proposed. The high light
induced LHCII dimerization is discussed as a potential element of the
photoprotective response in plants.
PMID- 28425026
TI - Photosynthetic responses to temperature across leaf-canopy-ecosystem scales: a 15
year study in a Californian oak-grass savanna.
AB - Ecosystem CO2 fluxes measured with eddy-covariance techniques provide a new
opportunity to retest functional responses of photosynthesis to abiotic factors
at the ecosystem level, but examining the effects of one factor (e.g.,
temperature) on photosynthesis remains a challenge as other factors may confound
under circumstances of natural experiments. In this study, we developed a data
mining framework to analyze a set of ecosystem CO2 fluxes measured from three
eddy-covariance towers, plus a suite of abiotic variables (e.g., temperature,
solar radiation, air, and soil moisture) measured simultaneously, in a
Californian oak-grass savanna from 2000 to 2015. Natural covariations of
temperature and other factors caused remarkable confounding effects in two
particular conditions: lower light intensity at lower temperatures and drier air
and soil at higher temperatures. But such confounding effects may cancel out. At
the ecosystem level, photosynthetic responses to temperature did follow a
quadratic function on average. The optimum value of photosynthesis occurred
within a narrow temperature range (i.e., optimum temperature, T opt): 20.6 +/-
0.6, 18.5 +/- 0.7, 19.2 +/- 0.5, and 19.0 +/- 0.6 degrees C for the oak canopy,
understory grassland, entire savanna, and open grassland, respectively. This
paradigm confirms that photosynthesis response to ambient temperature changes is
a functional relationship consistent across leaf-canopy-ecosystem scales.
Nevertheless, T opt can shift with variations in light intensity, air dryness, or
soil moisture. These findings will pave the way to a direct determination of
thermal optima and limits of ecosystem photosynthesis, which can in turn provide
a rich resource for baseline thresholds and dynamic response functions required
for predicting global carbon balance and geographic shifts of vegetative
communities in response to climate change.
PMID- 28425027
TI - 10-year results of On-X bileaflet mechanical heart valve in the aortic position:
low target INR regimen in Japanese.
AB - OBJECTIVES: This study was designed to establish clinical outcomes after aortic
valve replacement (AVR) with On-X bileaflet mechanical heart valve. METHODS:
Between 2006 and 2014, AVR was performed to 686 patients. Of them, 78 patients
using On-X valve were enrolled. The mean age was 65 +/- 11 years (ranged 33-85);
65% were men; and 81% were in sinus rhythm preoperatively. Calcific or
degenerative tricuspid aortic valve was present in 73%. Concomitant procedures
included coronary artery bypass grafting (22%), Bentall (8%), mitral valve
procedure (3%) and other (9%). They postoperatively received lower dose warfarin
[international normalized ratio (INR), 1.5-2.0] and 100 mg aspirin daily. The
follow-up duration averaged 5 years (386.6 patient-years). The follow-up rate was
97.3%. RESULTS: In-hospital mortality rates were 3.8% (n = 3). Late mortality
rates were 2.6% per patient-years (n = 10). Five-year Kaplan-Meier survival rates
were 84%. Freedom from major adverse valve-related stroke and cerebral bleeding
events was 93.3% (n = 5, 1.29% per patient-years) and 98.6% (n = 1, 0.26% per
patient-years, mild subdural hematoma). The incidence of stroke was two patients
of transient ischemic attack, two patients of paralytic event, one patient of
asymptomatic stroke (self-interruption of anticoagulation). The median INR was
1.92 +/- 0.53, ranged from 1.00 to 8.98 (n = 1181) and 51% of all measured INR
values were in the therapeutic range of 1.5-2.0. CONCLUSIONS: AVR using On-X
valve with low target INR regimen and low-dose aspirin resulted in a
significantly low risk of bleeding.
PMID- 28425028
TI - Energy harvesting from cerebrospinal fluid pressure fluctuations for self-powered
neural implants.
AB - In this paper, a novel method to generate electrical energy by converting
available mechanical energy from pressure fluctuations of the cerebrospinal fluid
within lateral ventricles of the brain is presented. The generated electrical
power can be supplied to the neural implants and either eliminate their battery
need or extend the battery lifespan. A diaphragm type harvester comprised of
piezoelectric material is utilized to convert the pressure fluctuations to
electrical energy. The pressure fluctuations cause the diaphragm to bend, and the
strained piezoelectric materials generate electricity. In the framework of this
study, an energy harvesting structure having a diameter of 2.5 mm was designed
and fabricated using microfabrication techniques. A 1:1 model of lateral
ventricles was 3D-printed from raw MRI images to characterize the harvester.
Experimental results show that a maximum power of 0.62 nW can be generated from
the harvester under similar physical conditions in lateral ventricles which
corresponds to energy density of 12.6 nW/cm2. Considering the available area
within the lateral ventricles and the size of harvesters that can be built using
microfabrication techniques it is possible to amplify to power up to 26 nW. As
such, the idea of generating electrical energy by making use of pressure
fluctuations within brain is demonstrated in this work via the 3D-printed model
system.
PMID- 28425029
TI - Comparison of a Novel Formulation of Abiraterone Acetate vs. the Originator
Formulation in Healthy Male Subjects: Two Randomized, Open-Label, Crossover
Studies.
AB - BACKGROUND AND OBJECTIVE: Abiraterone acetate is approved for the treatment of
metastatic castration-resistant prostate cancer. The originator abiraterone
acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic
variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is
a proprietary formulation (using SoluMatrix Fine Particle TechnologyTM) designed
to increase the oral bioavailability of abiraterone acetate. Here, we report on
two phase I studies in healthy male subjects aged 18-50 years. METHODS: In Study
101, 20 subjects were randomized in a crossover design to single doses of AAFP
100, 200, or 400 mg or OAA 1000 mg taken orally under fasting conditions. Results
suggested that AAFP 500 mg would be bioequivalent to OAA 1000 mg in the fasted
state. To confirm the bioequivalence hypothesis and to further expand the AAFP
dose range, in Study 102, 36 subjects were randomized in a crossover design to
single doses of AAFP 125, 500, or 625 mg or OAA 1000 mg. Both studies included a
7-day washout period between administrations. RESULTS: Dose-dependent increases
in the area under the plasma concentration-time curve and maximum plasma
concentration with AAFP were observed in both studies. The AAFP 500-mg
bioavailability relative to OAA 1000 mg measured by the geometric mean ratio for
area under the plasma concentration-time curve from time zero to the time of the
last quantifiable concentration was 93.4% (90% confidence interval 85.3-102.4),
area under the plasma concentration-time curve from time zero to infinity was
91.0% (90% confidence interval 83.3-99.4), and maximum plasma concentration was
99.8% (90% confidence interval 86.3-115.5). Dose proportionality was seen across
all AAFP dose levels (100-625 mg). Abiraterone acetate fine particle was found to
be safe and well tolerated in this study. CONCLUSION: Abiraterone acetate fine
particle 500 mg was demonstrated to be bioequivalent to OAA 1000 mg in healthy
volunteers under fasted conditions.
PMID- 28425030
TI - Hand-eye calibration for surgical cameras: a Procrustean Perspective-n-Point
solution.
AB - PURPOSE: Surgical cameras are prevalent in modern operating theatres often used
as surrogates for direct vision. A surgical navigational system is a useful
adjunct, but requires an accurate "hand-eye" calibration to determine the
geometrical relationship between the surgical camera and tracking markers.
METHODS: Using a tracked ball-tip stylus, we formulated hand-eye calibration as a
Perspective-n-Point problem, which can be solved efficiently and accurately using
as few as 15 measurements. RESULTS: The proposed hand-eye calibration algorithm
was applied to three types of camera and validated against five other widely used
methods. Using projection error as the accuracy metric, our proposed algorithm
compared favourably with existing methods. CONCLUSION: We present a fully
automated hand-eye calibration technique, based on Procrustean point-to-line
registration, which provides superior results for calibrating surgical cameras
when compared to existing methods.
PMID- 28425031
TI - The cytokine expression in synovial membrane and the relationship with pain and
pathological findings at hip arthroscopy.
AB - BACKGROUND: Synovial membrane inflammation is the most common finding presenting
during hip arthroscopy, and may play a role in hip pain. We sought to determine
the relationships between synovial cytokine levels, hip pain, and arthroscopic
findings of the hip joint. METHODS: We prospectively included 33 patients who
underwent arthroscopic hip surgery (34 hips). For all patients, radiographs and
severity of pain were evaluated preoperatively. During arthroscopy, we classified
the chondral injury and synovitis, noted the incidence of labral tear and its
instability, and a sample of the synovial membrane was harvested for quantitative
PCR to determine levels of TNFalpha, IL1beta, IL6, ADAMTS4, MMP1, and MMP3. The
relationships between the levels of these cytokines, severity of hip pain, and
the pathological findings during arthroscopy were examined. RESULTS: Pain
intensity and cytokine levels were not significantly different between patients
with labral tear or instability and those without. By contrast, the expression of
TNFalpha, IL1beta, IL6, and MMP1 mRNA was significantly higher in patients with
diffuse synovitis than in patients with focal synovitis. VAS score during rest
showed significant positive correlation with IL6 (r = 0.45, p < 0.01), while VAS
score on walking showed a positive correlation with TNFalpha (r = 0.47, p <
0.01), and ADAMTS4 (r = 0.51, p < 0.01). The modified Harris Hip pain score
showed a negative correlation with TNFalpha (r = -0.38, p = 0.04) and IL6 (r =
0.58, p < 0.01). CONCLUSIONS: The severity of synovitis and chondral injury are
considered to be more important in the pathology of hip pain than labral tear or
instability. Inflammatory cytokines, especially TNFalpha and IL6 might play an
important role in the pathogenesis of pain in patients indicated for hip
arthroscopy, possibly depending on the severity of synovitis.
PMID- 28425032
TI - Parenting in On/Off Relationships: The Link Between Relationship Churning and
Father Involvement.
AB - Family systems theory points to the interconnected nature of dyadic relationships
within the family unit, arguing for attention to how the parental relationship
shapes their ties to and interactions with their children. Grounded in family
systems theory, we consider how relationship churning-defined as being in an on
again/off-again relationship with the same partner-is associated with father
involvement. We use data from the Fragile Families and Child Wellbeing Study to
examine how father involvement among relationship churners compares with father
involvement among those in three other relationship types (measured during the
first five years of the focal child's life): stably together relationships,
stably broken-up relationships, and repartnered relationships. First, we find
that churning fathers remain more involved with their 9-year-old children than do
parents who stably break up or repartner, but they are less involved than those
who are stably together. Second, lower relationship quality among churners-and,
to a lesser extent, repartnering and childbearing with a new partner-explains
some of the differences in father involvement between churners and the stably
together. Third, these differences are most apparent among parents not living
together when father involvement is measured. Taken together, the focus on
relationship churning extends prior research on the association between
relationship transitions and father involvement by separating relationship
instability from partner change.
PMID- 28425033
TI - Strengths and Limitations of Using the Polypill in Cardiovascular Prevention.
AB - PURPOSE OF REVIEW: Polypill and its role in cardiovascular disease (CVD)
prevention has been extensively discussed and debated since the inception of the
concept in 2003. This article reviews the subsequent accumulated research in this
area. RECENT FINDINGS: Several short and intermediate to long-term studies with
different brands of polypills have analysed the impact of polypill in phase II
and III trials. The strengths of polypill that have emerged include better
adherence, equivalent or better risk factor control and quality of life among
polypill users as compared to usual care. The lurking limitations include
difficulty with dose adjustment to targets, fear of mass medicalisation and low
acceptability among physicians. The current literature supports polypill use in
reducing blood pressure and cholesterol levels for CVD prevention with
improvement in adherence to medication. However, the long-term outcome of
polypill on CVD events and mortality are unavailable and are currently being
studied in clinical trials.
PMID- 28425035
TI - A new ascaridid nematode, Mammalakis zambiensis n. sp. (Heterakoidea:
Kiwinematidae), from the mole rat Fukomys anselli (Burda, Zima, Scharff, Macholan
& Kawalika) (Rodentia: Bathyergidae) in Zambia.
AB - Mammalakis zambiensis n. sp. is described from the large intestine and caecum of
Fukomys anselli (Burda, Zima, Scharff, Macholan & Kawalika), a bathyergid rodent
endemic to Zambia. Morphological data for comparison with its three congeners, M.
macrospiculum (Ortlepp, 1939), M. spalacis (Marcu, 1930) and M. spalaxi (Kozlov &
Jangolenko, 1962) are provided. Based on studies of the type-material,
observations of hitherto undescribed morphological characters of M.
macrospiculum, a parasite of Bathyergus suillus (Schreber) (Hystricomorpha:
Bathyergidae) in South Africa, are presented. To date, the generic diagnosis of
Mammalakis Inglis, 1991 is based largely on characters of its type-species, M.
macrospiculum. In having three rounded lips, not set-off from the body, a stout
oesophagus with a flask-shaped posterior bulb, lateral alae that broaden on the
level of the precloacal sucker and cloaca, and mature eggs with a smooth shell,
M. zambienis n. sp. corresponds to the characters of the genus. However, the
presence of lips with anterior flanges that were observed in M. zambiensis n.
sp., and also for the first time in M. macrospiculum, are in contrast with the
current diagnosis of Mammalakis. Further studies will be needed to determine if
an amendment of the generic diagnosis is indicated.
PMID- 28425034
TI - The molluscum contagiosum virus death effector domain containing protein MC160
RxDL motifs are not required for its known viral immune evasion functions.
AB - The molluscum contagiosum virus (MCV) uses a variety of immune evasion strategies
to antagonize host immune responses. Two MCV proteins, MC159 and MC160, contain
tandem death effector domains (DEDs). They are reported to inhibit innate immune
signaling events such as NF-kappaB and IRF3 activation, and apoptosis. The RxDL
motif of MC159 is required for inhibition of both apoptosis and NF-kappaB
activation. However, the role of the conserved RxDL motif in the MC160 DEDs
remained unknown. To answer this question, we performed alanine mutations to
neutralize the arginine and aspartate residues present in the MC160 RxDL in both
DED1 and DED2. These mutations were further modeled against the structure of the
MC159 protein. Surprisingly, the RxDL motif was not required for MC160's ability
to inhibit MAVS-induced IFNbeta activation. Further, unlike previous results with
the MC159 protein, mutations within the RxDL motif of MC160 had no effect on the
ability of MC160 to dampen TNF-alpha-induced NF-kappaB activation. Molecular
modeling predictions revealed no overall changes to the structure in the MC160
protein when the amino acids of both RxDL motifs were mutated to alanine (DED1 =
R67A D69A; DED2 = R160A D162A). Taken together, our results demonstrate that the
RxDL motifs present in the MC160 DEDs are not required for known functions of the
viral protein.
PMID- 28425036
TI - Lobocapillaria austropacifica n. g., n. sp. (Nematoda: Capillariidae) from the
obtuse barracuda Sphyraena obtusata Cuvier (Sphyraenidae, Perciformes) off
eastern Australia.
AB - Based on light and scanning electron microscopical studies, a new nematode
parasite, Lobocapillaria austropacifica n. sp. (Capillariidae), is described from
the gall-bladder of the marine fish (obtuse barracuda) Sphyraena obtusata Cuvier
(Perciformes: Sphyraenidae) from off the eastern Pacific coast of Australia, for
which a new genus Lobocapillaria n. g. is established. This new genus is mainly
characterised by a single row of stichocytes, the presence of two large,
conspicuously elongated lateral caudal lobes and a pair of subventral papillae at
their base in males, a flat spicule distended laterally towards its proximal end
and provided with superficial rough transverse grooves, a spicular canal and a
very long, aspinose spicular sheath with a conspicuous expansion near its
proximal end when evaginated. Capillaria sphyraeni Parukhin, 1971 is transferred
to Lobocapillaria as L. sphyreni (Parukhin, 1971) n. comb. A key to capillariid
genera containing species parasitic in fishes is provided.
PMID- 28425037
TI - A new species of Caryospora Leger, 1904 (Apicomplexa: Eimeriidae) from the
Guanabara spotted night snake Siphlophis pulcher (Raddi) (Reptilia: Dipsadidae)
in the Atlantic Forest, Brazil.
AB - A new coccidian species of the genus Caryospora Leger, 1904 (Apicomplexa,
Eimeriidae) is described based on material from the Guanabara spotted night snake
Siphlophis pulcher (Raddi) (Reptilia: Dipsadidae) in a coastal area of the
Atlantic Forest in Ilha Grande Island, state of Rio de Janeiro, southeastern
Brazil. Caryospora ceadsensis n. sp. possesses spheroidal to slightly
subspheroidal oocysts measuring 17-24 * 17-24 (22.1 * 22.0) um, with a c.1.3 um
thick bi-layered wall (inner layer smooth, outer layer slightly striated),
length/width (L/W) ratio of 1.0-1.1 (1.0) and a highly refractive polar granule.
Sporocysts are ellipsoidal, 11-17 * 10-13 (14.7 * 11.2) um, with a L/W ratio of
1.0-1.5 (1.3), with a nipple-like Stieda body (1.1 um high and 2.9 um wide) and a
large, bubble-shaped sub-Stieda body 1.7 um high and 3.8 um wide (1.0-2.0 * 3.0
4.5 um). Sporocyst residuum composed of granules of differing sizes. Sporozoites
with striations. This is the sixth record of a species of Caryospora in snakes of
the family Dipsadidae in Brazil.
PMID- 28425038
TI - A new species Selenonycha insperata n. sp. (Acariformes: Syringophilidae) from
the bare-faced ibis Phimosus infuscatus (Lichtenstein) (Pelecaniformes:
Threskiornithidae) as an example of host-switching event.
AB - A new quill mite species of the family Syringophilidae (Acariformes: Prostigmata:
Cheyletoidea) is described from Phimosus infuscatus (Lichtenstein)
(Pelecaniformes: Threskiornithidae) in Argentina. Selenonycha insperata n. sp.
differs from other species of the genus Selenonycha Kethley, 1970 by the presence
of wing-like cuticular projections of coxal fields III-IV situated in front of
trochanters (vs absence). An unexpected finding of this species on a bird of the
family Threskiornithidae (Pelecaniformes) is discussed as an example of host
shift. Additionally, a key to the species of the genus is provided.
PMID- 28425039
TI - Disaggregation Following Agonist-Induced Platelet Activation in Patients on Dual
Antiplatelet Therapy.
AB - Disaggregation as the difference between maximal and final platelet aggregation
by light transmission aggregometry indicates the stability of platelet
aggregates. We evaluated the extent of disaggregation after platelet stimulation
with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine,
and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual
antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel
(group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent
elective angioplasty and stenting, whereas all patients included in groups 2 and
3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent
PCI. Significant differences between maximal and final platelet aggregation were
observed with all agonists throughout the groups (all p<0.001). Disaggregation
was highest using AA (clopidogrel 36.5%; prasugrel/ticagrelor 100%) and ADP
(clopidogrel 21.7%; prasugrel/ticagrelor 100%). In contrast, low disaggregation
was observed after platelet stimulation with collagen and TRAP-6 in clopidogrel
treated patients, and after platelet stimulation with collagen and epinephrine in
prasugrel- and ticagrelor-treated patients. In conclusion, pathways of platelet
activation that are not inhibited by standard antiplatelet therapy allow
persisting platelet aggregation and may at least in part be responsible for
adverse ischemic events.
PMID- 28425040
TI - Schiff base complexes of copper and zinc as potential anti-colitic compounds.
AB - The design, synthesis and activity of polymodal compounds for the treatment of
inflammatory bowel disease are reported. The compounds, being based on a metal
Schiff base motif, are designed to degrade during intestinal transit to release
the bioactive components in the gut. The compounds have been developed sequential
with the biomodal compounds combining copper or zinc with a salicylaldehyde
adduct. These compounds were tested in a formalin induced colonic inflammation
model in BK:A mice. From these studies a trimodal compound based on a zinc Schiff
base analogue of sulfasalazine was designed. This was tested against a
trinitrobenzenesulfonic acid (TNB) induced colitic model in Wistar rats. The use
of two models allows us to test our compounds in both an acute and a chronic
model. The trimodal compound reported is observed to provide anticolitic
properties in the chronic TNB induced colitis model commensurate with that of
SASP. However, the design of trimodal compound still has the capacity for further
development. This the platform reported may offer a route into compounds which
can markedly outperform the anti-colitic properties of SASP.
PMID- 28425041
TI - Familial amyloid cardiomyopathy masquerading as chronic Guillain-Barre syndrome:
things are not always what they seem.
AB - Familial amyloid cardiomyopathy is a challenging condition that mimics many other
diseases, particularly in patients with pronounced neurological presentations and
unexplained or equivocal cardiac abnormalities. In this case, a 57-year-old man
was admitted for outpatient cardiological evaluation of progressive right heart
failure and limb paraesthesias. The patient presented with hypertension, chronic
Guillain-Barre syndrome, and sick sinus syndrome. Transthoracic echocardiograms
showed a thickened ventricular wall and enlarged atrium. Tissue Doppler showed a
restrictive filling pattern. Transthyretin (TTR)-associated amyloidosis, which
was revealed by abdominal fat-pad biopsy and DNA analysis, explained the
concurrence of independent pathological features, including neuropathy and
cardiac involvement. Genetic testing identified a G > T mutation in exon 4 of the
transthyretin (TTR) gene. This mutation resulted in the alanine-to-serine
substitution at amino acid position 117. Moreover, genetic testing confirmed that
the patient's asymptomatic son carried the same amyloidogenic TTR mutation. Given
these findings, the diagnosis of familial amyloid cardiomyopathy, which was
misdiagnosed as chronic Guillain-Barre syndrome, was proposed.
PMID- 28425042
TI - Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL
patient: a case report.
AB - Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic
sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined
with all-trans-retinotic acid (ATRA), ATO has become the first-line induction
therapy in treating acute promyelocytic leukemia (APL). The most common side
effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium
retention, and nervous system damage. In this report, we present a rare side
effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with
ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath,
myodynia, elevated creatine kinase, and acute renal insufficiency. This report
describes the first case of ATO-induced rhabdomyolysis.
PMID- 28425043
TI - Innovative development path of ethnomedicines: a case study.
AB - Innovative development extends the vitality of ethnomedicines. Developing
ethnomedicines is not only beneficial to the public but also to the related
industry and transforms economic growth, driving local social and economic
development further. Its economic benefit can be used to optimize and promote the
hardware and software of the platform, as well as support the sustainable
development of ethnomedicines. Apart from research and discussion on the
innovative development of ethnomedicines on the basis of theory and regulations,
this series of articles also summarizes cases that are conducive to the overall
understanding of the necessity and feasibility of the innovative development. In
terms of industrial development, large enterprises and products, such as Yunnan
Baiyao, Guizhou Miao ethnomedicines, Cheezheng Tibetan Medicine, products
developed from Dengzhanhua (Erigeron breviscapus), the Gold series of Yi
ethnomedicines, and products developed from Sanqi (Panax notoginseng), in China
are introduced and summarized, focusing on resource superiority, sustainable
innovation, standard research and development, and production, as well as
intellectual property protection.
PMID- 28425044
TI - Systematic review for geo-authentic Lonicerae Japonicae Flos.
AB - In traditional Chinese medicine, Lonicerae Japonicae Flos is commonly used as
anti-inflammatory, antiviral, and antipyretic herbal medicine, and geo-authentic
herbs are believed to present the highest quality among all samples from
different regions. To discuss the current situation and trend of geo-authentic
Lonicerae Japonicae Flos, we searched Chinese Biomedicine Literature Database,
Chinese Journal Full-text Database, Chinese Scientific Journal Full-text
Database, Cochrane Central Register of Controlled Trials, Wanfang, and PubMed. We
investigated all studies up to November 2015 pertaining to quality assessment,
discrimination, pharmacological effects, planting or processing, or ecological
system of geo-authentic Lonicerae Japonicae Flos. Sixty-five studies mainly
discussing about chemical fingerprint, component analysis, planting and
processing, discrimination between varieties, ecological system, pharmacological
effects, and safety were systematically reviewed. By analyzing these studies, we
found that the key points of geo-authentic Lonicerae Japonicae Flos research were
quality and application. Further studies should focus on improving the quality by
selecting the more superior of all varieties and evaluating clinical
effectiveness.
PMID- 28425045
TI - Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential
biomarker for the diagnosis of infectious diseases.
AB - Sensitive and useful biomarkers for the diagnosis and prognosis of infectious
diseases have been widely developed. An example of these biomarkers is triggering
receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor
expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation
by activating the TREM-1/DAP12 pathway. This pathway is triggered by the
interaction of TREM-1 with ligands or stimulation by bacterial
lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are
secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be
directly tested in human body fluids and well-known biomarker for infectious
diseases. sTREM-1 level can be potentially used for the early diagnosis and
prognosis prediction of some infectious diseases, including infectious pleural
effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g.,
Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g.,
Aspergillus infection), and burn-related infections. sTREM-1 is a more sensitive
and specific biomarker than traditional indices, such as C-reactive protein and
procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a
feasible biomarker for the targeted therapy and rapid and early diagnosis of
infectious diseases.
PMID- 28425046
TI - MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT.
AB - Glioblastoma is one of the most frequent and aggressive brain tumors.
Accumulating evidence indicates that microRNAs are involved in glioma
proliferation, invasion and drug resistance. Previous studies showed that miR-198
is downregulated in glioblastoma. However, the function of miR-198 in
glioblastoma is still unclear. In this study, we report that miR-198 levels were
greatly downregulated in glioblastoma specimens and decreased expression of miR
198 was associated with poor prognosis in patients with glioblastoma. And
overexpression of miR-198 increased chemosensitivity to temozolomide in vitro and
in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct
target of miR-198, and miR-198 overexpression prevented the protein translation
of MGMT. Furthermore, overexpression of MGMT restored miR-198-induced
chemosensitivity to temozolomide. Moreover, the protein levels of MGMT were
upregulated in clinical glioblastoma specimens and inversely correlated with miR
198 levels. In conclusion, our studies revealed that MiR-198 induces
chemosensitivity in glioblastoma by targeting MGMT and that miR-198 may be used
as a new diagnostic marker and therapeutic target for glioblastoma in the future.
PMID- 28425047
TI - Can anti-vascular endothelial growth factor antibody reverse radiation necrosis?
A preclinical investigation.
AB - Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising
new treatment for late time-to-onset radiation-induced necrosis (RN). We sought
to evaluate and validate the response to anti-VEGF antibody in a mouse model of
RN. Mice were irradiated with the Leksell Gamma Knife PerfexionTM and then
treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN
progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR.
Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry
staining were used to validate the response to treatment. After treatment, both
post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased
(P < 0.001), while the lesion volumes for the control group increased. The
abnormally high apparent diffusion coefficient (ADC) for RN also returned to the
ADC range for normal brain following treatment (P < 0.001). However, typical RN
pathology was still present histologically. Large areas of focal calcification
were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia
inducible factor 1-alpha (HIF-1alpha) were continually upregulated in both the
anti-VEGF and control groups. Despite improvements observed radiographically
following anti-VEGF treatment, lesions were not completely resolved
histologically. The subsequent calcification and the continued upregulation of
VEGF and HIF-1alpha merit further preclinical/clinical investigation.
PMID- 28425049
TI - Erratum to: Successful Management of Zoon's Balanitis with Topical Mupirocin
Ointment: A Case Report and Literature Review of Mupirocin-Responsive Balanitis
Circumscripta Plasmacellularis.
PMID- 28425048
TI - Biopsy targeting with dynamic contrast-enhanced versus standard neuronavigation
MRI in glioma: a prospective double-blinded evaluation of selection benefits.
AB - Current biopsy planning based on contrast-enhanced T1W (CET1W) or FLAIR sequences
frequently delivers biopsy samples that are not in concordance with the gross
tumor diagnosis. This study investigates whether the quantitative information of
transfer constant Ktrans maps derived from T1W dynamic contrast-enhanced MRI (DCE
MRI) can help enhance the quality of biopsy target selection in glioma. 28
patients with suspected glioma received MRI including DCE-MRI and a standard
neuronavigation protocol of 3D FLAIR- and CET1W data sets (0.1 mmol/kg
gadobutrol) at 3.0 T. After exclusion of five cases with no Ktrans-elevation, 2-6
biopsy targets were independently selected by a neurosurgeon (samples based on
standard imaging) and a neuroradiologist (samples based on kinetic parameter
Ktrans) per case and tissue samples corresponding to these targets were collected
by a separate independent neurosurgeon. Standard technique and Ktrans-based
samples were rated for diagnostic concordance with the gross tumor resection
reference diagnosis (67 WHO IV; 24 WHO III and II) by a neuropathologist blinded
for selection mode. Ktrans-based sample targets differed from standard technique
sample targets in 90/91 cases. More Ktrans-based than standard imaging-based
samples could be extracted. Diagnoses from Ktrans-based samples were more
frequently concordant with the reference gross tumor diagnoses than those from
standard imaging-based samples (WHO IV: 30/39 vs. 11/20; p = 0.08; WHO III/II:
12/13 vs. 6/11; p = 0.06). In 4/5 non-contrast-enhancing gliomas, Ktrans-based
selection revealed significantly more accurate samples than standard technique
sample-selection (10/12 vs. 2/8 samples; p = 0.02). If Ktrans elevation is
present, Ktrans-based biopsy targeting provides significantly more diagnostic
tissue samples in non-contrast-enhancing glioma than selection based on CET1W and
FLAIR-weighted images alone.
PMID- 28425050
TI - Oxidative protein modification alters proteostasis under acute hypobaric hypoxia
in skeletal muscles: a comprehensive in vivo study.
AB - While numerous maladies are associated with hypobaric hypoxia, muscle protein
loss is an important under studied topic. Hence, the present study was designed
to investigate the mechanism of muscle protein loss at HH. SD rats were divided
into normoxic rats, while remaining rats were exposed to simulated hypoxia
equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at
25 degrees C for 6, 12, and 24 h. Post-exposure rats were sacrificed and
analysis was performed. Ergo, muscle loss-related changes were observed at 12 and
24 h post-HH exposure. An increased reactive oxygen species production and
decreased thiol content was observed in HH-exposed rats. This disturbance caused
substantial protein oxidative modification in the form of protein carbonyl
content and advanced oxidation protein products. The analysis showed increase
levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate
with MDA, protein hydroperoxide, and protein-MDA product. These changes were also
in agreement with increase in lipid hydroperoxides and MDA content. HSP-70 and
HSP-60 were upregulated significantly, and this finding is corroborated with
increase in ER stress biomarker, GRP-78. Overloading of cells with misfolded
proteins further activated degradative machinery. Consequently, pro-apoptotic
signaling cascade, caspase-3, and C/EBP homologous protein were also activated in
24-h HH exposure. Release of tryptophan and tyrosine was also increased with 24-h
HH exposure, indicated protein degradation. Elevation in resting intracellular
calcium ion, [Ca2+]i, was also observed at 12- and 24-h HH exposure. The present
study provides a detailed mechanistic representation of muscle protein loss
during HH exposure.
PMID- 28425051
TI - Upregulation and phosphorylation of HspB1/Hsp25 and HspB5/alphaB-crystallin after
transient middle cerebral artery occlusion in rats.
AB - Ischemic stroke leads to cellular dysfunction, cell death, and devastating
clinical outcomes. The cells of the brain react to such a cellular stress by a
stress response with an upregulation of heat shock proteins resulting in
activation of endogenous neuroprotective capacities. Several members of the
family of small heat shock proteins (HspBs) have been shown to be
neuroprotective. However, yet no systematic study examined all HspBs during
cerebral ischemia. Here, we performed a comprehensive comparative study
comprising all HspBs in an animal model of stroke, i.e., 1 h transient middle
cerebral artery occlusion followed by 23 h of reperfusion. On the mRNA level out
of the 11 HspBs investigated, HspB1/Hsp25, HspB3, HspB4/alphaA-crystallin,
HspB5/alphaB-crystallin, HspB7/cvHsp, and HspB8/Hsp22 were significantly
upregulated in the peri-infarct region of the cerebral cortex of infarcted
hemispheres. HspB1 and HspB5 reached the highest mRNA levels and were also
upregulated at the protein level, suggesting that these HspBs might be
functionally most relevant. Interestingly, in the infarcted cortex, both HspB1
and HspB5 were mainly allocated to neurons and to a lesser extent to glial cells.
Additionally, both proteins were found to be phosphorylated in response to
ischemia. Our data suggest that among all HspBs, HspB1 and HspB5 might be most
important in the neuronal stress response to ischemia/reperfusion injury in the
brain and might be involved in neuroprotection.
PMID- 28425052
TI - DMSO Assisted Electrospray Ionization for the Detection of Small Peptide Hormones
in Urine by Dilute-and-Shoot-Liquid-Chromatography-High Resolution Mass
Spectrometry.
AB - The mobile phase additive (DMSO) has been described as a useful tool to enhance
electrospray ionization (ESI) of peptides and proteins. So far, this technique
has mainly been used in proteomic/peptide research, and its applicability in a
routine clinical laboratory setting (i.e., doping control analysis) has not been
described yet. This work provides a simple, easy to implement screening method
for the detection of doping relevant small peptides (GHRPs, GnRHs, GHS, and
vasopressin-analogues) with molecular weight less than 2 kDa applying DMSO in the
mobile phase. The gain in sensitivity was sufficient to inject the urine samples
after a 2-fold dilution step omitting a time consuming sample preparation. The
employed analytical procedure was validated for the qualitative determination of
36 compounds, including 13 metabolites. The detection limits (LODs) ranged
between 50 and 1000 pg/mL and were compliant with the 2 ng/mL minimum detection
level required by the World Anti-Doping Agency (WADA) for all the target
peptides. To demonstrate the feasibility of the work, urine samples obtained from
patients who have been treated with desmopressin or leuprolide and urine samples
that have been declared as adverse analytical findings were analyzed. Graphical
Abstract ?.
PMID- 28425053
TI - What Demographic and Clinical Characteristics Correlate With Expectations With
Trapeziometacarpal Arthritis?
AB - BACKGROUND: Pretreatment variables have been shown to be associated with the
fulfillment of patient expectations, yet in treating thumb trapeziometacarpal
osteoarthritis (OA) it remains unclear how patient expectations correlate with
the effectiveness of treatment. An increased understanding of the variables that
affect patient expectations enables tailored patient education and patient
provider communication. QUESTIONS/PURPOSES: (1) Is there a correlation between
patient demographics and clinical characteristics, and the expectations the
patients have when seeking treatment for trapeziometacarpal OA? (2) What factors
are independently associated with the total expectations score and frequency of
expecting "back to normal" among patients treated for trapeziometacarpal OA?
METHODS: Between March 2011 and October 2013, 89 patients of all 96 eligible
patients seeking treatment for trapeziometacarpal OA were approached and agreed
to participate in this study. Participants completed a validated expectations
survey measuring the number of expectations and the degree of improvement
expected. Comparative analysis of demographic and clinical characteristics and
multivariate regression analysis against patients' expectations were performed to
assess and identify factors that correlate with the number and degree of
expectations. Sample size was determined with an a priori power analysis (with
80% power and statistical significance set at p < 0.05), which showed that 88
patients were needed to detect the minimal clinical difference of 12 points in
the Michigan Hand Questionnaire; we then increased this by 10% to allow for
potential dropouts. RESULTS: After controlling for potential confounding
variables such as age, hand dominance, and work status, the following factors
were associated with a higher expectations score: choice of surgery (beta = 11.5;
95% CI, 0.7-23.8; p = 0.044), female gender (beta = 19.0; 95% CI, 5.3-32.7; p =
0.007), and dominant side affected (beta = -41.6; 95% CI, -63.7 to -19.5; p <
0.001). For the frequency of "back to normal" responses, surgical treatment (beta
= 7.4; 95% CI, 2.3-12.4; p = 0.005) and history of previous injury (beta = 8.2;
95% CI, 0.1-16.3; p = 0.047) were independently associated factors after
controlling for confounding variables. There were no independent associations
with age, marital status, work status, depression or anxiety, or prior
contralateral surgery. CONCLUSIONS: Patients whose dominant side was affected,
were female, and chose surgical treatment, had higher total expectations.
Patients who reported an antecedent injury and chose surgical treatment more
frequently expected a return to normal. With identification of these factors,
orthopaedic surgeons can recognize patients who are prone to higher expectations,
and, thus, have the opportunity to implement efficient pretreatment education. In
addition, identification of specific factors enables a focused measure of the
effect of these factors on the fulfillment of expectations. LEVEL OF EVIDENCE:
Level II, prognostic study.
PMID- 28425054
TI - Can a Three-Component Prosthesis be Used for Conversion of Painful Ankle
Arthrodesis to Total Ankle Replacement?
AB - BACKGROUND: In patients with painful ankle arthrodesis, the surgical treatment is
challenging, and may include takedown of ankle arthrodesis and conversion to a
total ankle replacement (TAR). This procedure is technically demanding given the
altered anatomy after arthrodesis. Few studies have evaluated TAR in the setting
of prior arthrodesis. QUESTIONS/PURPOSES: (1) What intraoperative and
perioperative complications were observed in patients who underwent conversion of
an ankle arthrodesis to a TAR? (2) Was durable fixation achieved at short term,
and what was the alignment of the components? (3) What subsequent surgical
procedures were performed, including revisions? (4) What improvements were
observed in pain, tibiotalar range of motion (ROM), and quality of life? METHODS:
Between January 2007 and December 2014, 18 patients with a painful ankle
arthrodesis underwent conversion to TAR at our tertiary referral center. During
this period, the indications for conversion of ankle arthrodesis to TAR were
tibiotalar nonunion or malunion after attempted arthrodesis in patients who
declined revision ankle arthrodesis. The goal of revision surgery was to help
patients regain hindfoot mobility and to decrease pain. During the study period,
all patients who met indications were treated with a conversion procedure. Of the
18 patients included, 14 were men and four were women. The mean age of the
patients was 51 +/- 7 years. The mean followup was 54 +/- 27 months, with no loss
to follow up observed. The initial ankle arthrodesis was performed 6 +/- 3.5
years before conversion to TAR. In all patients, the conversion to TAR was
performed using a nonconstrained cementless three-component prosthesis.
Intraoperative and postoperative complications, revision procedures, and
prosthesis component loosening were evaluated. Weightbearing radiographs were
used to determine the angular alignment of the tibial and talar components using
alpha/beta/gamma angles and to analyze the bone-implant interface.
Osseointegration was defined as visible trabecular structures at the bone-implant
interface without radiolucent lines. The criteria for radiographic loosening was
defined as subsidence or migration of prosthesis components and/or a cystic
lesion with a diameter at least 2 mm. Clinical assessment included pain
evaluation, measurement of ankle ROM, and quality of life. RESULTS: Two of the 18
patients sustained an intraoperative medial malleolar fracture. In three
patients, delayed wound healing was observed. At latest followup, four patients
had incomplete osseointegration (posterior quarter of the bone-prosthesis
interface on the tibial side). None of the 18 patients had prosthesis loosening.
In all patients, both components were neutrally aligned. Two patients had painful
arthrofibrosis with reduced ROM, which we treated with an open arthrolysis and
exchange of mobile-bearing inlay; one other patient is considering a revision for
substantial tibial component medial tilt with collapse of the medial arch. At the
latest followup, the mean dorsiflexion and plantar flexion were 8.5 degrees +/-
3 degrees and 15 degrees +/- 5 degrees , respectively. The mean visual analog
scale (VAS) score decreased from 9 +/- 0.8 to 1.7 +/- 1.6 (p < 0.001). The Short
Form Health Survey questionnaire (SF-36) physical and mental outcome scores
improved from 34 +/- 5 to 74 +/- 11 (p < 0.001) and from 49 +/- 4 to 75.5 +/- 7
(p < 0.001). CONCLUSIONS: Conversion of an ankle arthrodesis to a TAR is a
technically challenging procedure. In this small series, it was associated with
frequent complications including arthrofibrosis, and functional outcomes
including postoperative ROM were lower than reported for primary TAR. However,
pain and function did improve. Further studies are necessary to address long-term
clinical and radiographic outcomes in this patient cohort. LEVEL OF EVIDENCE:
Level IV, therapeutic study.
PMID- 28425055
TI - What are the Oncologic and Functional Outcomes After Joint Salvage Resections for
Juxtaarticular Osteosarcoma About the Knee?
AB - BACKGROUND: Joint salvage surgery for patients with juxtaarticular osteosarcoma
remains challenging, especially when the tumor invades the epiphysis. Because
patients are surviving longer with current chemotherapy regimens, it is
advantageous to retain native joints if possible, especially in young patients.
However, the results using joint-preserving tumor resections in this context have
not been well characterized. QUESTIONS/PURPOSES: (1) What are the functional
outcomes after limb salvage surgery at a minimum of 3 years? (2) What are the
oncologic outcomes? (3) Is joint salvage surgery for epiphyseal tumors associated
with an increased risk of local recurrence compared with metaphyseal tumors not
invading the epiphysis? (4) What are the complications associated with joint
salvage surgery? METHODS: Between 2004 and 2013, we treated 117 patients with
juxtaarticular osteosarcoma; of those, 43 (38%) were treated with joint salvage
surgery, and 41 (95%) of the 43 patients are included in our study. The other two
(5%) were lost to followup before 3 years (mean, 4.4 years; range, 3-11 years,).
During the period in question, we generally performed joint salvage surgery in
these patients when they had a favorable response to chemotherapy, did not have a
pathologic fracture or extrusion of the tumor into the joint, and did not have a
whole-epiphyseal osteolytic lesion, a large mass, or obvious neurovascular
involvement. This report is a followup of an earlier study; the current study
includes an additional nine patients, and additional followup of a mean of 19
months for the patients included in the earlier report. We ascertained overall
survival and survival free from local recurrence which was estimated using the
Kaplan-Meier method, functional status of the limb which was evaluated using the
Musculoskeletal Tumor Society (MSTS)-93 scoring system, and recorded
reconstructive complications including infection, fracture, skin necrosis, and
nonunion. We compared oncologic and functional outcomes between patients with (n
= 28) and without tumor extension to epiphysis (n =13). We also compared
oncologic and functional outcomes among patients with different adjuvant
treatments including microwave ablation (n = 11), cryoablation (n = 12), and
navigation-assisted osteotomy (n = 5). Complications were tallied using records
from our institutional database. RESULTS: The overall Kaplan-Mayer survival rate
was 82% (95% CI, 104-128 months) at 5 years. The overall Kaplan-Meier
survivorship from local recurrence was 91% at 5 years (95% CI, 115-133 months).
Three patients had a local recurrence, but none had local recurrence in or close
to the remaining epiphysis. The MSTS scores ranged from 22 to 30 points, with a
median of 28. There were no differences in survival rate, local recurrence, or
MSTS scores between patients with a tumor that did not invade the epiphysis and
those in whom the tumor did invade the epiphysis. There were differences in MSTS
scores among patients with epiphyseal tumor extension in which different adjuvant
techniques, including microwave ablation, cryoablation, and navigation-assisted
osteotomy, were used. Additional surgical procedures were recorded for 10
patients (24%). Osteonecrosis of the residual epiphysis was detected 13 patients
(31%). CONCLUSIONS: Our findings suggest it is possible to salvage joints in
selected patients with juxtaarticular osteosarcoma around the knee. The patients
who have a favorable response to chemotherapy are the best candidates for this
approach. Future studies might explore the role of adjuvant techniques of
microwave ablation and cryoablation, particularly when the tumor invades the
epiphysis, and whether resections can be facilitated with navigation. LEVEL OF
EVIDENCE: Level IV, therapeutic study.
PMID- 28425057
TI - Quantifying synergies in two-versus-one situations in team sports: An example
from Rugby Union.
AB - Collective behaviors in team sports result in players forming interpersonal
synergies that contribute to performance goals. Because of the huge amount of
variables that continuously constrain players' behavior during a game, the way
that these synergies are formed remain unclear. Our aim was to quantify
interpersonal synergies in the team sport of Rugby Union. For that purpose we
used the Uncontrolled Manifold Hypothesis (UCM) to identify interpersonal
synergies that are formed between ball carrier and support player in two-versus
one situations in Rugby Union. The inter-player angle close to the moment of the
pass was used as a performance variable and players running lines velocities as
task-relevant elements. Interpersonal synergies (UCM values above 1) were found
in 19 out of 55 trials under analysis, which means that on 34% of the trials, the
players' running line velocities contribute to stabilizing the inter-player angle
close the moment of the pass. The strength of the synergy fluctuates over time
indicating the existence of a location effect during attack phases in Rugby
Union. UCM analysis shows considerable promise as a performance analysis tool in
team sports to discriminate between skilled sub-groups of players.
PMID- 28425056
TI - Ischemic Heart Disease: Special Considerations in Cardio-Oncology.
AB - OPINION STATEMENT: The interplay and balance between the competing morbidity and
mortality of cardiovascular diseases and cancer have a significant impact on both
short- and long-term health outcomes of patients who survived cancer or are being
treated for cancer. Ischemic heart disease in patients with cancer or caused by
cancer therapy is a clinical problem of emerging importance. Prompt recognition
and optimum management of ischemic heart disease mean that patients with cancer
can successfully receive therapies to treat their malignancy and reduce morbidity
and mortality due to cardiovascular disease. In this sense, the presence of
cancer and cancer-related comorbidities (e.g., thrombocytopenia, propensity to
bleed, thrombotic status) substantially complicates the management of
cardiovascular diseases in cancer patients. In this review, we will summarize the
current state of knowledge on the management strategies for ischemic disease in
patients with cancer, focusing on the challenges encountered when addressing
these complexities.
PMID- 28425058
TI - Finding the traces of behavioral and cognitive processes in big data and
naturally occurring datasets.
AB - Today, people generate and store more data than ever before as they interact with
both real and virtual environments. These digital traces of behavior and
cognition offer cognitive scientists and psychologists an unprecedented
opportunity to test theories outside the laboratory. Despite general excitement
about big data and naturally occurring datasets among researchers, three "gaps"
stand in the way of their wider adoption in theory-driven research: the
imagination gap, the skills gap, and the culture gap. We outline an approach to
bridging these three gaps while respecting our responsibilities to the public as
participants in and consumers of the resulting research. To that end, we
introduce Data on the Mind ( http://www.dataonthemind.org ), a community-focused
initiative aimed at meeting the unprecedented challenges and opportunities of
theory-driven research with big data and naturally occurring datasets. We argue
that big data and naturally occurring datasets are most powerfully used to
supplement-not supplant-traditional experimental paradigms in order to understand
human behavior and cognition, and we highlight emerging ethical issues related to
the collection, sharing, and use of these powerful datasets.
PMID- 28425059
TI - GraphCom: A multidimensional measure of graphic complexity applied to 131 written
languages.
AB - We report a new multidimensional measure of visual complexity (GraphCom) that
captures variability in the complexity of graphs within and across writing
systems. We applied the measure to 131 written languages, allowing comparisons of
complexity and providing a basis for empirical testing of GraphCom. The measure
includes four dimensions whose value in capturing the different visual properties
of graphs had been demonstrated in prior reading research-(1) perimetric
complexity, sensitive to the ratio of a written form to its surrounding white
space (Pelli, Burns, Farell, & Moore-Page, 2006); (2) number of disconnected
components, sensitive to discontinuity (Gibson, 1969); (3) number of connected
points, sensitive to continuity (Lanthier, Risko, Stolz, & Besner, 2009); and (4)
number of simple features, sensitive to the strokes that compose graphs (Wu,
Zhou, & Shu, 1999). In our analysis of the complexity of 21,550 graphs, we (a)
determined the complexity variation across writing systems along each dimension,
(b) examined the relationships among complexity patterns within and across
writing systems, and (c) compared the dimensions in their abilities to
differentiate the graphs from different writing systems, in order to predict
human perceptual judgments (n = 180) of graphs with varying complexity. The
results from the computational and experimental comparisons showed that GraphCom
provides a measure of graphic complexity that exceeds previous measures in its
empirical validation. The measure can be universally applied across writing
systems, providing a research tool for studies of reading and writing.
PMID- 28425061
TI - Gray matter and white matter changes in non-demented amyotrophic lateral
sclerosis patients with or without cognitive impairment: A combined voxel-based
morphometry and tract-based spatial statistics whole-brain analysis.
AB - The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that
patients show structural changes within but also beyond the motor cortex and
corticospinal tract and furthermore outside the frontal lobes, even if frank
dementia is not detected. The aim of the present study was to investigate both
gray matter (GM) and white matter (WM) changes in non-demented amyotrophic
lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor
and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy
controls (HC) underwent 3D-T1-weighted and 30-directional diffusion-weighted
imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial
statistics analysis were performed to examine GM volume (GMV) changes and WM
differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD,
respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal
and cerebellar areas and increased GMV in right supplementary motor area, while
ALS-plus patients showed diffuse GMV reduction in primary motor cortex
bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor
patients had increased GMV in left precuneus compared to ALS-plus patients. We
also found decreased FA and increased RD in the corticospinal tract bilaterally,
the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased
FA and increased AD and RD in motor and several WM tracts in ALS-plus patients,
compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM
abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and
identifies early extra-motor brain pathology in ALS patients without cognitive
impairment (ALS-motor).
PMID- 28425060
TI - Positron emission tomography assessment of cerebral glucose metabolic rates in
autism spectrum disorder and schizophrenia.
AB - Several models have been proposed to account for observed overlaps in clinical
features and genetic predisposition between schizophrenia and autism spectrum
disorder. This study assessed similarities and differences in topological
patterns and vectors of glucose metabolism in both disorders in reference to
these models. Co-registered 18fluorodeoxyglucose PET and MRI scans were obtained
in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to
map cortical and subcortical regions of interest. Metabolic rates were compared
between three diagnostic groups using univariate and multivariate repeated
measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects
were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus,
amygdala and medial thalamic nuclei; rates were increased in the occipital
cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects
metabolic rates were decreased in the parietal lobe, frontal premotor and eye
fields areas, and amygdala; rates were increased in the posterior cingulate,
occipital cortex, hippocampus and basal ganglia. In relation to controls,
subjects with ASD and schizophrenia showed opposite changes in metabolic rates in
the primary motor and somatosensory cortex, anterior cingulate and hypothalamus;
similar changes were found in prefrontal and occipital cortices, inferior
parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD
appear to be associated with a similar pattern of metabolic abnormalities in the
social brain. Divergent maladaptive trade-offs, as postulated by the diametrical
hypothesis of their evolutionary relationship, may involve a more circumscribed
set of anterior cingulate, motor and somatosensory regions and the specific
cognitive functions they subserve.
PMID- 28425062
TI - Patients' Lived Experiences of Nocturia: A Qualitative Study of the Evening, the
Night, and the Next Day.
AB - BACKGROUND: Nocturia, waking to urinate two or more times during the night, is a
chronic condition associated with significant patient burden due to sleep
disruption. This study aimed to explore the lived experiences of patients with
nocturia in terms of the disruption to their lives during the night and day.
METHODS: Adult patients in the US diagnosed with nocturia were recruited for face
to-face qualitative interviews. Thematic analysis of patients' narratives, taking
a phenomenological interpretative approach, summarised their experiences
throughout the night and day, including any apparent contrasts between patients.
RESULTS: Twenty patients (10 male, 10 female) aged between 39 and 80 years,
averaging three night-time voids, were interviewed. Analysis revealed that
nocturia has a substantial impact on sleep quality and quantity, with the
frequency of night-time voids a key driver of this. In addition to night-time
phenomena, patients faced various difficulties the next day, including day-time
tiredness, lack of energy and concerns related to emotional wellbeing, social
functioning and cognitive functioning. All of these limited patients' capacity to
work, perform daily activities or fulfil role responsibilities. Patients'
lifestyles influenced experience, where younger patients in employment more
readily emphasised the day-time physical and psychosocial burdens. Patients
employed coping behaviours in an attempt to lessen the severity of nocturia and
its impact, which were both physician-led and self-taught. CONCLUSIONS: While the
symptom of nocturia only occurs during the night, the impact is longer lasting,
affecting functioning and wellbeing throughout the following day. Patients'
circumstances can affect the extent of their burden; recognising this can improve
effective delivery of patient-centred care.
PMID- 28425063
TI - Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and
Metabolism on Stem Cell Potency Loss and Miscarriage.
AB - Data from in vitro and in vivo models suggest that malnutrition and stress
trigger adaptive responses, leading to small for gestational age (SGA)
blastocysts with fewer cell numbers. These stress responses are initially
adaptive, but become maladaptive with increasing stress exposures. The common
stress responses of the blastocyst-derived stem cells, pluripotent embryonic and
multipotent placental trophoblast stem cells (ESCs and TSCs), are decreased
growth and potency, and increased, imbalanced and irreversible differentiation.
SGA embryos may fail to produce sufficient antiluteolytic placental hormone to
maintain corpus luteum progesterone secretion that provides nutrition at the
implantation site. Myriad stress inputs for the stem cells in the embryo can
occur in vitro during in vitro fertilization/assisted reproductive technology
(IVF/ART) or in vivo. Paradoxically, stresses that diminish stem cell growth lead
to a higher level of differentiation simultaneously which further decreases ESC
or TSC numbers in an attempt to functionally compensate for fewer cells. In
addition, prolonged or strong stress can cause irreversible differentiation.
Resultant stem cell depletion is proposed as a cause of miscarriage via a "quiet"
death of an ostensibly adaptive response of stem cells instead of a reactive,
violent loss of stem cells or their differentiated progenies.
PMID- 28425065
TI - Changes in perfusion and diffusion in the endplate regions of degenerating
intervertebral discs: a DCE-MRI study.
PMID- 28425066
TI - Maverick total disc replacement in a real-world patient population: a
prospective, multicentre, observational study.
PMID- 28425067
TI - Answer to the Letter to the Editor of A. Agarwal et al. concerning "Rod fracture
lengthening intervals in traditional growing rods: is there a relationship?" by
P. Hosseini et al. Eur Spine J (2016); doi:10.1007/s00586-016-4786-8.
PMID- 28425064
TI - A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip
Platforms.
AB - Metastasis accounts for most cancer-related deaths. The majority of solid
cancers, including those of the breast, colorectum, prostate and skin,
metastasize at significant levels to the liver due to its hemodynamic as well as
tumor permissive microenvironmental properties. As this occurs prior to detection
and treatment of the primary tumor, we need to target liver metastases to improve
patients' outcomes. Animal models, while proven to be useful in mechanistic
studies, do not represent the heterogeneity of human population especially in
drug metabolism lack proper human cell-cell interactions, and this gap between
animals and humans results in costly and inefficient drug discovery. This
underscores the need to accurately model the human liver for disease studies and
drug development. Further, the occurrence of liver metastases is influenced by
the primary tumor type, sex and race; thus, modeling these specific settings will
facilitate the development of personalized/targeted medicine for each specific
group. We have adapted such all-human 3D ex vivo hepatic microphysiological
system (MPS) (a.k.a. liver-on-a-chip) to investigate human micrometastases. This
review focuses on the sources of liver resident cells, especially the iPS cell
derived hepatocytes, and examines some of the advantages and disadvantages of
these sources. In addition, this review also examines other potential challenges
and limitations in modeling human liver.
PMID- 28425068
TI - Analysis of cervical sagittal alignment change following correction of thoracic
and thoracolumbar Scheuermann's kyphosis.
AB - PURPOSE: To analyse pre-operative and post-operative changes of cervical sagittal
alignment (CSA) in Scheuermann's kyphosis (SK) patients. METHODS: 64 SK and 33
control patients were retrospectively reviewed. Whole spine X-rays obtained at
pre-op, 3 months post-op and at latest follow-up were reviewed and ten separate
CSA radiological parameters were measured. Patients were divided in three groups:
thoracic SK (TK group, apex T6-T9, n = 40), thoracolumbar SK (TLK group, apex T10
T12, n = 24), and controls. RESULTS: Pre-operative C2-C7 lordosis was 21.1
degrees +/- 8.1 degrees (TK), 6.1 degrees +/- 5.0 degrees (TLK), and 11.4
degrees +/- 8.3 degrees in control group and correlated significantly with T1
slope in both SK groups (r = 0.640, r = 0.772). Pre-operative T1 slope was
dependent on deformity type, thoracic kyphosis (TK, beta = 0.445), and lumbar
lordosis (LL, beta = -0.354). At final follow-up C2-C7 lordosis decreased to 15.7
degrees +/- 5.5 degrees in TK, and increased to 12.1 degrees +/- 4.1 degrees
in TLK group. C2-C7 lordosis changes linearly correlated with T1 slope changes
post-operatively (r = 0.721). Post-operative T1 slope showed linear correlation
with post-operative changes in TK (beta = 0.728) and pelvic tilt (PT, beta =
0.539) in TK, and LL (beta = -0.669), thoracolumbar kyphosis (TLK, beta =
0.434), and PT (beta = 0.760) in TLK group. CONCLUSIONS: Our study suggests that
SK is not a homogenous group of patients. Two patterns of pre- and post-operative
CSA are demonstrated in TK and TLK groups. T1 slope is the most important
parameter in determining pre-operative CSA and correlates with other regional
anatomical parameters (TK and LL). Post-operative CSA adaptations also correlate
with T1 slope post-operative changes. However, post-surgical T1 slope correlates
with different parameters in the two SK groups (TK and PT in TK group; TLK, LL,
and PT in TLK group).
PMID- 28425069
TI - A prospective serial MRI study following acute traumatic cervical spinal cord
injury.
AB - PURPOSE: In acute traumatic cervical spinal cord injury (SCI) patients, we sought
to characterize how objective MRI measures of injury change during the first 3
week post-injury. METHODS: Six MRI scans each were planned in 19 cervical SCI
patients within the first 3 week post-injury. Length of cord edema, maximum
spinal cord compression, maximum canal compromise, and presence and length of
hematoma were measured. RESULTS: Length of spinal cord edema increased in the
first 48 h after SCI, followed by a gradual decrease in the 3 weeks after injury.
This was predominantly seen in the more severe grades of SCI. Hematoma in the
spinal cord was seen in all AIS-A and B patients. CONCLUSION: This study
demonstrates the dynamic nature of imaging changes on MRI in the first weeks
after injury and highlights the importance of taking into account the timing of
imaging when interpreting objective measures of damage.
PMID- 28425070
TI - H emibagrus sp. as a potential bioindicator of hazardous metal pollution in
Selangor River.
AB - The spatial distributions of Na, Mg, K, Ca, Cr, Fe, Ni, Cu, Zn, As, Se and Pb in
Hemibagrus sp. from Selangor River and a reference site were determined with
inductively coupled plasma-mass spectrometer, in comparison to the levels in
their surrounding water body and sediments. The results demonstrated significant
differences in elemental accumulation pattern in different fish tissues
originated from both sites. The variations observed were mainly subjected to
their metabolic activities, and also the influence of the surrounding medium. In
general, the liver tends to accumulate higher concentration of metals followed by
the gills, and muscle tissues. The data also indicate associations between the
concentrations of metal contaminants measured in the fish and the levels observed
at the sites. The concentrations of hazardous metals As, Se and Pb in all the
studied tissues reflect the influence of anthropogenic inputs. This suggests the
potential utility of widely available Hemibagrus sp. as a valuable bioindicator
of metal pollution in environmental monitoring and assessment.
PMID- 28425071
TI - Micro-spatial variation of elemental distribution in estuarine sediment and their
accumulation in mangroves of Indian Sundarban.
AB - This work describes the micro-spatial variation of elemental distribution in
estuarine sediment and bioaccumulation of those elements in different mangrove
species of the Indian Sundarbans. The potential ecological risk due to such
elemental load on this mangrove-dominated habitat is also discussed. The
concentrations of elements in mangrove leaves and sediments were determined using
energy-dispersive X-ray fluorescence spectroscopy. Sediment quality and potential
ecological risks were assessed from the calculated indices. Our data reflects
higher concentration of elements, e.g., Al, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn,
and Pb, in the sediment, as compared to that reported by earlier workers.
Biological concentration factors for K, Ca, Mn, Fe, Cu, and Zn in different
mangroves indicated gradual elemental bioaccumulation in leaf tissues (0.002
1.442). Significant variation was observed for elements, e.g., Ni, Mn, and Ca, in
the sediments of all the sites, whereas in the plants, significant variation was
found for P, S, Cl, K, Ca, Mn, Fe, Cu, and Zn. This was mostly due to the
differences in uptake and accumulation potential of the plants. Various sediment
quality indices suggested the surface sediments to be moderately contaminated and
suffering from progressive deterioration. Cu, Cr, Zn, Mn, and Ni showed higher
enrichment factors (0.658-1.469), contamination factors (1.02-2.7), and geo
accumulation index (0.043-0.846) values. The potential ecological risk index
values considering Cu, Cr, Pb, and Zn were found to be within "low ecological
risk" category (20.04-24.01). However, Cr and Ni in the Sundarban mangroves
exceeded the effect range low and probable effect level limits. Strong
correlation of Zn with Fe and K was observed, reflecting their similar
transportation and accumulation process in both sediment and plant systems. The
plant-sediment elemental correlation was found to be highly non-linear,
suggesting role of some physiological and edaphic factors in the accumulation
process. Overall, the study of micro-spatial distribution of elements can act as
a useful tool for determining health of estuarine ecosystem.
PMID- 28425072
TI - Comment on: "Evaluation of Facebook and Twitter Monitoring to Detect Safety
Signals for Medical Products: An Analysis of Recent FDA Safety Alerts".
PMID- 28425073
TI - Molecular therapy of primary hyperoxaluria.
AB - During the last few decades, the molecular understanding of the mechanisms
involved in primary hyperoxalurias (PHs) has set the stage for novel therapeutic
approaches. The availability of PH mouse models has facilitated preclinical
studies testing innovative treatments. PHs are autosomal recessive diseases where
the enzymatic deficit plays a central pathogenic role. Thus, molecular therapies
aimed at restoring such deficit or limiting the consequences of the metabolic
derangement could be envisioned, keeping in mind the specific challenges posed by
the cell-autonomous nature of the deficiency. Various molecular approaches like
enzyme replacement, substrate reduction, pharmacologic chaperones, and gene and
cell therapies have been explored in cells and mouse models of disease. Some of
these proof-of-concept studies have paved the way to current clinical trials on
PH type 1, raising hopes that much needed treatments will become available for
this severe inborn error of metabolism.
PMID- 28425074
TI - LincRNa-p21: function and mechanism in cancer.
AB - In view of the rapid development of gene chips and high-throughput sequencing
technology, noncoding RNAs (ncRNas) form a high percentage of the mammalian
genome. Two major subgroups of ncRNAs that have been identified are the long
ncRNAs (lncRNas) and the microRNAs. A number of studies in the past few years
have showed crucial functions for lncRNas in cancer. LincRNa-p21 as a p53
dependent transcriptional target gene and a potential diagnostic marker is
involved in proliferation, cell cycle, metabolism and reprogramming. In addition,
more researches revealed that lincRNa-p21 is associated with cancer progression
and contributed to the treatment and prognosis of cancer. In this review, we
briefly summarize the function and molecular mechanisms of lincRNa-p21 in cancer
and its regulation for the genes expression .
PMID- 28425075
TI - Technical note: real-time web-based wireless visual guidance system for
radiotherapy.
AB - Describe a Web-based wireless visual guidance system that mitigates issues
associated with hard-wired audio-visual aided patient interactive motion
management systems that are cumbersome to use in routine clinical practice. Web
based wireless visual display duplicates an existing visual display of a
respiratory-motion management system for visual guidance. The visual display of
the existing system is sent to legacy Web clients over a private wireless
network, thereby allowing a wireless setting for real-time visual guidance. In
this study, active breathing coordinator (ABC) trace was used as an input for
visual display, which captured and transmitted to Web clients. Virtual reality
goggles require two (left and right eye view) images for visual display. We
investigated the performance of Web-based wireless visual guidance by quantifying
(1) the network latency of visual displays between an ABC computer display and
Web clients of a laptop, an iPad mini 2 and an iPhone 6, and (2) the frame rate
of visual display on the Web clients in frames per second (fps). The network
latency of visual display between the ABC computer and Web clients was about 100
ms and the frame rate was 14.0 fps (laptop), 9.2 fps (iPad mini 2) and 11.2 fps
(iPhone 6). In addition, visual display for virtual reality goggles was
successfully shown on the iPhone 6 with 100 ms and 11.2 fps. A high network
security was maintained by utilizing the private network configuration. This
study demonstrated that a Web-based wireless visual guidance can be a promising
technique for clinical motion management systems, which require real-time visual
display of their outputs. Based on the results of this study, our approach has
the potential to reduce clutter associated with wired-systems, reduce space
requirements, and extend the use of medical devices from static usage to
interactive and dynamic usage in a radiotherapy treatment vault.
PMID- 28425076
TI - Monoclonal gammopathy of renal significance (MGRS): the characteristics and
significance of a new meta-entity.
AB - Monoclonal gammopathy of renal significance (MGRS) is a new nosological group of
entities (meta-entity) defined in 2012, whose pathogenesis depends on monoclonal
immunoglobulins (Ig) secreted by low-grade lymphoproliferative disorders, which
belong to M-protein-related diseases. Renal damage is the result of monoclonal Ig
deposit or its activity as autoantibodies, which can compromise any nephronal
area. MGRS does not include kidney diseases produced by high-grade
lymphoproliferative disorders as well as those whose pathogenesis are independent
of monoclonal Ig (such as drug toxicity or metabolic disorders). The importance
of this hemato-nephrological meta-entity is based on two aspects: First, it is
associated with increased morbidity and mortality, including recurrence in post
renal transplant or its appearance as "de novo" after it; and second, it usually
improves after treating the plasmocyte or lymphocyte clone responsible, leading
to the elimination of M-protein. Between low-grade lymphoproliferative disorders,
monoclonal gammopathy of undetermined significance (MGUS) requires special
consideration for two reasons: First, it is the disorder most related to MGRS;
second, when MGUS progresses to MGRS, effective treatment against toxic underline
clone should be performed taking into account the nephrological perspective.
PMID- 28425077
TI - Unexpected and striking effect of heparin-free dialysis on cytokine release.
AB - Heparin (both unfractionated and low molecular weight) is not only a potent
anticoagulant but also has many pleiotropic effects, some of which are mediated
by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin
as an anticoagulant and without systemic anticoagulation (heparin-grafted
membrane-Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1),
endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed
with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured
after such a dialysis. During HD with Evodial, the intradialytic levels of all
three cytokines were 2-3 folds lower. The between-anticoagulant differences were
significant over time for all three cytokines: MCP-1 (P < 0.001), ES (P < 0.001)
and Act-A (P < 0.001). This striking effect of heparin-free dialysis with Evodial
membrane may be beneficial not only because it reduces the possibility of
bleeding complications but also because it might reduce proinflammatory cytokine
concentration and therefore contribute to the improvement in endothelial
function. Further studies are needed to determine whether it has a positive
effect on morbidity and mortality of maintenance HD patients.
PMID- 28425079
TI - Outcome of patients with septic shock and high-dose vasopressor therapy.
AB - BACKGROUND: Despite the dissemination of international guidelines, mortality from
septic shock remains high. Norepinephrine is recommended as first-line
vasopressor therapy with a target mean arterial pressure of 65 mmHg. High-dose
vasopressor (HDV) may also be required. This study aimed to assess survival in
patients with septic shock requiring HDV. We conducted a retrospective study of
patients admitted between January 2008 and December 2013 to a 13-bed ICU for
septic shock and receiving high-dose vasopressor therapy (defined by a dose >1
ug/kg/min). Primary outcome was 28-day mortality (D28). Secondary outcomes were
90-day mortality (D90), organ failure score (SOFA), duration of organ failure,
duration and dosage of vasopressor agent and ischemic complications. RESULTS: In
our cohort of 106 patients, mortality reached 60.4% at D28 and 66.3% at D90. One
in two patients died before D10. The weight-based mean dose of vasopressor (WMD)
represented the best prognostic factor. Using a cutoff of 0.75 ug/kg/min, WMD was
associated with mortality with a sensitivity of 73% and specificity of 74%. The
mortality rate reached 86.4% when WMD was above the cutoff value and associated
with a SOFA score >10. Digital or limb necrosis was documented in 6 patients
(5.7%). CONCLUSIONS: In total, 40% of septic shock patients receiving high-dose
vasopressor therapy survived at day 28 after admission. A WMD cutoff value of
0.75 ug/kg/min, associated with a >10 SOFA score, was a strong predictor of
death. These results provide insights into outcome of refractory septic shock,
showing that administration of high-dose vasopressor may indeed be useful in
these patients.
PMID- 28425080
TI - Monitoring of Paternal Mitochondrial Degradation in Caenorhabditis elegans.
AB - In Caenorhabditis elegans embryos, paternally inherited mitochondria and their
mitochondrial DNA are degraded via selective autophagy called allophagy
(allogeneic organelle autophagy). This is a developmentally programmed autophagy
and combined with C. elegans genetics and in vivo imaging provides a unique
opportunity to analyze selective autophagy under physiological conditions.
PMID- 28425078
TI - Involvement of interstitial cells of Cajal in bladder dysfunction in mice with
experimental autoimmune encephalomyelitis.
AB - BACKGROUND: Bladder dysfunction is an important symptom of experimental
autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced
upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4
(EP4) in the bladder was accompanied by bladder dysfunction. Although many other
studies have evaluated the lower urinary tract symptoms in multiple sclerosis,
the mechanism remains unclear. OBJECTIVES: To investigate the effects of
interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic
bladder model induced by experimental autoimmune encephalomyelitis. MATERIALS AND
METHODS: The EAE model was induced by a previously established method, and
bladder functions in mice were evaluated. Bladders were harvested for the
analysis of ICCs and the genes associated with bladder mechanosensation including
pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and
western blotting. The stem cell factor cytokine (SCF) was intraperitoneally
injected at the beginning of EAE onset. RESULTS: EAE mice developed profound
bladder dysfunction characterized by significant urine retention, increased
micturition and decreased urine output per micturition. EAE induced a significant
decrease in c-Kit expression and ICCs number. EAE also induced a significant
increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of
these pathological changes. CONCLUSIONS: ICCs and stem cell factor play an
important role in EAE-induced bladder dysfunction, which may be used as
therapeutic options in treating patients with multiple sclerosis-related bladder
dysfunction.
PMID- 28425081
TI - Perisinusoidal bone marrow involvement by lymphoma.
PMID- 28425082
TI - Discriminating between positional and non-positional obstructive sleep apnea
using some clinical characteristics.
AB - PURPOSE: The primary objective of this paper was to identify significant factors
associated with positional Obstructive Sleep Apnea (POSA) and to provide a
clinical tool for discriminating non positional from POSA. Secondary objectives
were about estimating the prevalence of POSA, comparing the polysomnographic
variables across POSA and non-POSA patients. METHODS: This was a cross sectional
study on 278 patients who completed an overnight sleep study for OSA assessment.
Patients were aged over 18 years, without central sleep apnea or narcolepsy and
slept no less than 20 min in a non-supine position. POSA was defined as a total
apnea/hypopnea index (AHI) >=5 and a ratio supine AHI/non-supine AHI >=2. The
binary logistic regression was used for modeling the likelihood for OSA patient
to be positional, and the LASSO method was used for selecting the optimal set of
clinical characteristics associated with POSA. RESULTS: Overall, 53% of patients
had POSA. These patients were younger (p = 0.005), had lower BMI (p < 0.0001),
lower prevalence of hypertension (p = 0.006), lower Berlin (p = 0.01), and lower
STOP (p = 0.001) scores compared to non-POSA patients. Neck and waist
circumference were higher in non-POSA (p = 0.005, p = 0.009, respectively)
patients. Age, BMI, DBP, Mallampati, and Berlin scores were found to be the best
clinical characteristics associated with POSA with an area under the ROC curve
(AUC) of 0.71 (95% CI [0.63, 0.78]). CONCLUSIONS: Half of patients referred for
the sleep study had POSA. Age, BMI, DBP, Mallampati, and Berlin scores, put
together, were shown to act as good clinical characteristics to discriminate
between POSA and non-POSA patients.
PMID- 28425083
TI - Restless legs syndrome/Willis-Ekbom disease prevalence in beta thalassemia
patients.
AB - PURPOSE: Both beta thalassemia and restless legs syndrome (RLS) patients share
some common pathophysiological characteristics related to iron handling. In the
present study, the aim was to explore the prevalence of RLS as well as to explore
potential association between the syndrome and various quality of life-related
parameters in a sample of beta thalassemia patients. METHODS: One hundred
fourteen (age 40 +/- 11 yr, 59 M/55F) beta thalassemia patients participated in
this cross-sectional descriptive study. Patients were screened for RLS based on
the international RLS study group diagnostic criteria as well as a battery of
validated questionnaires. RESULTS: The prevalence of RLS in this sample of beta
thalassemia patients was zero. The quality of life score was low (78 +/- 18).
Iron levels were within normal range (191 +/- 66 mcg/dL) while ferritin levels
were high as expected (1836 +/- 225 ng/dL). CONCLUSIONS: Our sample of patients
comes from central Greece where the prevalence of RLS in the general population
is 4% while in renal failure patients is 27%. To our surprise, there was no
presence of RLS among this sample of beta thalassemia patients. The adequate
levels of iron and ferritin often seen in these patients could be the reason of
the absence of RLS symptoms.
PMID- 28425084
TI - Independent dose verification for brain stereotactic radiotherapy using different
add-on micro multi-leaf collimators.
AB - An add-on micro multi-leaf collimator (mMLC) is used for stereotactic
radiosurgery (SRS) and brain stereotactic radiotherapy (SRT), in which rotational
radiotherapy may make more complex and time-consuming. We performed a
retrospective study of an independent dose calculation verification for brain SRS
and SRT in two institutions to show the accuracy of the verification system and
propose a tolerance value for the verification. Several comparisons of static
plans and patients' plans were conducted using a phantom measurement, and
patients' plans using the patients' own computed tomography image. We evaluated
the accuracy of the Clarkson-based dose calculation based on either the
equivalent square field formed by the mMLC or by the collimator jaws to determine
the collimator scatter factor (S c). The results for the static plans showed good
agreement (<1%), except when we used a 1 cm2 field size (<4%). The phantom
measurements for the patients' plans showed deviations of 0.1 +/- 2.3 and 1.2 +/-
1.6% (2 SD) for the treatment planning system and the verification system,
respectively. The patients' plans showed a deviation of 2.0 +/- 2.1% (2 SD).
Depending on the mMLC system, the S c was calculated using the equivalent field
size formed by the mMLC. In this study, we suggest a tolerance level for the
brain SRS and SRT of 2-3.5%. However, beam modeling in the treatment planning
system would affect the deviation. The S c should be computed according to the
size of the collimator fitted to the MLC.
PMID- 28425086
TI - The clinical benefits of denosumab for prophylaxis of steroid-induced
osteoporosis in patients with pulmonary disease.
AB - : Previous reports demonstrated that bone density decreased rapidly during the
initial few months of steroid therapy and continued decreasing at a rate of 2 to
4% annually. Our data indicates that denosumab can also play a role in the
treatment of osteoporosis in the steroid-taking population. INTRODUCTION:
Respiratory physicians are often faced with the dilemma that long-term steroid
use will deteriorate bone mineral density and quality. Previous reports
demonstrated that bone density decreased 8 to 12% during the initial few months
of steroid therapy then continued decreasing at a rate of 2 to 4% annually.
Several prospective trials revealed that denosumab increased bone density in
patients with osteoporosis [2-4] and decreased the rate of occurrence of
fractures. The long-term efficacy of denosumab for glucocorticoid-induced
osteoporosis, however, has not yet been proven. MATERIALS: This has been an
ongoing prospective study since 2014. In our respiratory centre, the first
preventative measure used to combat glucocorticoid-induced osteoporosis (GIO) is
oral bisphosphonates. Thirty-six patients were enlisted, and their treatment
courses were changed from oral bisphosphonate, if administered, to the
subcutaneous injection of denosumab 60 mg every 6 months, combined with a daily
oral intake of DENOTAS(r) chewable combination tablets. The primary efficacy
measures were changes in lumbar spine (LS) bone mineral density (BMD) and femoral
BMD from baseline at 4, 8, 12 and 28 months. RESULTS: At the 12-month follow-up,
bone mineral density in the lumbar spine area of these patients increased by
3.2%, while bone mineral density in the hip area showed no significant increase.
At the 28-month follow-up, 25 patients were still included in this study. Femoral
BMD at 28 months increased significantly from the 12-month follow-up (P =
0.0259), though the first 12 months showed no significant increase. LS BMD
continued to increase through the 28-month period. CONCLUSIONS: Very little is
known regarding the active prevention of GIO. Our data indicates that denosumab
can play a promising role in the treatment of GIO.
PMID- 28425088
TI - Commentary on: Zhou C, Byard RW. Septic ketoacidosis-a potentially lethal entity
with renal tubular epithelial vacuolization. J Forensic Sci 2017;62(1):122-5.
PMID- 28425087
TI - Peer Connect for African American breast cancer survivors and caregivers: a train
the-trainer approach for peer support.
AB - Racial disparities in breast cancer survivorship are a major concern nationally.
How survivors cope with cancer and re-frame their lives is a critical part of
survivorship. Community-academic research partnerships may facilitate access to
much-needed psychosocial support for African American survivors and caregivers in
rural areas, but drivers of successful intervention implementation are not well
understood. The purpose of this study was to describe the training and evaluation
of Community Coaches and Guides (i.e., peer supporters) using the Peer Connect
program for African American breast cancer survivors and caregivers. Community
engagement strategies were used to implement the training component of Peer
Connect, an evidence-based program grounded in the Diffusion of Innovation Theory
utilizing motivational interviewing techniques (MI) and a "train-the-trainer"
model. Quantitative and qualitative methods examined implementation outcomes of
feasibility, MI fidelity, and acceptability-precursor outcomes that must be
achieved before examining intervention impact vis-a-vis changes in support care.
Training was feasible to implement and replicable by the trained Community
Coaches. Beyond feasibility and replicability, success was modest regarding MI
fidelity. Benefits (e.g., serving as role models and having safe sources of
support) and lessons learned (e.g., need for additional quality control) were
identified as both facilitators and barriers to implementation and as factors
that could impact the effectiveness of community-engaged programs to improve
survivorship outcomes. Peer Connect, like other programs that employ community
engagement strategies, holds promise to meet the psychosocial support needs of
diverse rural cancer survivor populations.
PMID- 28425085
TI - UK clinical guideline for the prevention and treatment of osteoporosis.
AB - INTRODUCTION: In 2008, the UK National Osteoporosis Guideline Group (NOGG)
produced a guideline on the prevention and treatment of osteoporosis, with an
update in 2013. This paper presents a major update of the guideline, the scope of
which is to review the assessment and management of osteoporosis and the
prevention of fragility fractures in postmenopausal women and men age 50 years or
over. METHODS: Where available, systematic reviews, meta-analyses and randomised
controlled trials were used to provide the evidence base. Conclusions and
recommendations were systematically graded according to the strength of the
available evidence. RESULTS: Review of the evidence and recommendations are
provided for the diagnosis of osteoporosis, fracture-risk assessment, lifestyle
measures and pharmacological interventions, duration and monitoring of
bisphosphonate therapy, glucocorticoid-induced osteoporosis, osteoporosis in men,
postfracture care and intervention thresholds. CONCLUSION: The guideline, which
has received accreditation from the National Institute of Health and Care
Excellence (NICE), provides a comprehensive overview of the assessment and
management of osteoporosis for all healthcare professionals who are involved in
its management.
PMID- 28425089
TI - High diagnostic yield of clinically unidentifiable syndromic growth disorders by
targeted exome sequencing.
AB - BACKGROUND: As syndromic short stature and overgrowth are heterogeneous and the
list of causative genes is rapidly expanding, there is an unmet need for
identifying genetic causes based on conventional gene testing or karyotyping.
Early diagnosis leads to the proper management of the patient and providing
genetic counseling for family members at risk in a timely manner. MATERIALS AND
METHODS: We conducted targeted exome sequencing to identify the genetic causes of
undiagnosed syndromic short stature or overgrowth in 15 pediatric patients from
13 families in Korea. We applied targeted exome sequencing using the Next Seq
platform and a TruSight One panel. RESULTS: Among the 13 families, 6 different
disorders in 8 patients with short stature or overgrowth were identified, and the
diagnostic yield was 46.2%. One boy with overgrowth had a TGFB3 gene mutation. In
the short stature group, Coffin-Lowry syndrome (CLS), trichorhinophalangeal
syndrome, DYRK1A haploinsufficiency syndrome, short stature with optic atrophy
and Pelger-Huet anomaly syndrome with recurrent hepatitis, and type 4 Meier
Gorlin syndrome were identified. One CLS patient had a co-existing monogenic
disease, congenital glaucoma, caused by the compound heterozygote mutations of
the CYP1B1 gene. CONCLUSION: Targeted exome sequencing is a powerful method for
diagnosing syndromic growth disorders. It enables us to understand molecular
pathophysiology and investigate new treatments for growth disorders.
PMID- 28425090
TI - Determinants of the postpericardiotomy syndrome: a systematic review.
AB - BACKGROUND: Postpericardiotomy syndrome (PPS) is a common complication following
cardiac surgery; however, the exact pathogenesis remains uncertain. Identifying
risk factors of PPS might help to better understand the syndrome. The aim of this
study was to provide an overview of existing literature around determinants of
PPS in adult cardiac surgery patients. MATERIAL AND METHODS: Two independent
investigators performed a systematic search in MEDLINE, EMBASE and the Cochrane
Central Register. The search aimed to identify studies published between January
1950 and December 2015, in which determinants of PPS were reported. RESULTS: A
total of 19 studies met the selection criteria. In these studies, 14 different
definitions of PPS were used. The median incidence of PPS was 16%. After quality
assessment, seven studies were considered eligible for this review. Lower
preoperative interleukin-8 levels and higher postoperative complement conversion
products were associated with a higher risk of PPS. Among other clinical factors,
a lower age, transfusion of red blood cells and lower preoperative platelet and
haemoglobin levels were associated with a higher risk of PPS. Colchicine use
decreased the risk of PPS. CONCLUSION: We found that both the inflammatory
response and perioperative bleeding and coagulation may play a role in the
development of PPS, suggesting a multifactorial aetiology of the syndrome. Due to
a lack of a uniform definition of PPS in the past, study comparability was poor
across the studies.
PMID- 28425091
TI - Marine Bioluminescence: Measurement by a Classical Light Sensor and Related
Foraging Behavior of a Deep Diving Predator.
AB - Bioluminescence is produced by a broad range of organisms for defense, predation
or communication purposes. Southern elephant seal (SES) vision is adapted to low
intensity light with a peak sensitivity, matching the wavelength emitted by
myctophid species, one of the main preys of female SES. A total of 11 satellite
tracked female SESs were equipped with a time-depth-light 3D accelerometer (TDR10
X) to assess whether bioluminescence could be used by SESs to locate their prey.
Firstly, we demonstrated experimentally that the TDR10-X light sensor was
sensitive enough to detect natural bioluminescence; however, we highlighted a low
distance detection of the sensor. Then, we linked the number of prey capture
attempts (PCAs), assessed from accelerometer data, with the number of detected
bioluminescence events. PCA was positively related to bioluminescence, which
provides strong support that bioluminescence is involved in predator-prey
interactions for these species. However, the limitations of the sensor did not
allow us to discern whether bioluminescence (i) provided remote indication of the
biological richness of the area to SES, (ii) was emitted as a mechanic reaction
or (iii) was emitted as a defense mechanism in response to SES behavior.
PMID- 28425092
TI - Coffee consumption and the risk of colorectal cancer by anatomical subsite in
Japan: Results from the HERPACC studies.
AB - Consumption of coffee, a popular beverage worldwide, has been associated with
lower colorectal cancer (CRC) risk. Although CRC exhibits different biological
characteristics by anatomical subsite, the possibly heterogeneous impact of
coffee on CRC by anatomical subsite has remained unclear. Here, we conducted two
case-control studies to examine the association between coffee consumption and
CRC risk as well as risk by anatomic subsite among Japanese using data from the
Hospital-based Epidemiological Research Program at Aichi Cancer Center I and II
(HERPACC-I and II). Subjects were enrolled in HERPACC-I between 1988 and 2000 and
in HERPACC-II between 2001 and 2005. Coffee consumption was measured with a self
administered questionnaire. A conditional logistic regression model was used to
calculate odds ratios (ORs) of CRC with coffee consumption, adjusted for
potential confounders of age, smoking, alcohol drinking, red meat intake, BMI,
exercise, family history of CRC, and diabetes mellitus history. We estimated
summary ORs by pooling study-specific ORs with a fixed effects model. In total,
2,696 CRC cases and 13,480 non-cancer outpatients as controls were included.
Overall, compared to non-drinkers, ORs of less than 1 cup/day, 1-2 cups/day and 3
or more cups/day for CRC were 0.88 (95% CI: 0.77-1.00), 0.90 (95% CI: 0.80-1.01)
and 0.78 (95% CI: 0.65-0.92), respectively (trend-p = 0.009). Subsite-specific
analysis revealed a significant inverse linear trend between coffee consumption
and distal colon cancer (p-trend = 0.048), and a tendency toward a lower risk of
rectal cancer (p-trend = 0.068). These findings suggest that coffee consumption
might impact the prevention of CRC, especially distal colon cancer.
PMID- 28425093
TI - Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and
Meta-analysis.
AB - OBJECTIVES: To investigate whether low-dose aspirin (<300 mg/d) can influence the
onset of cognitive impairment or dementia in observational studies and improve
cognitive test scores in randomized controlled trials (RCTs) in participants
without dementia. DESIGN: Systematic review and meta-analysis. SETTING:
Observational and interventional studies. PARTICIPANTS: Individuals with no
dementia or cognitive impairment initially. MEASUREMENTS: Odds ratios (ORs) and
95% confidence intervals (CIs), adjusted for the maximum number of covariates
from each study, were used to summarize data on the incidence of dementia and
cognitive impairment in observational studies. Standardized mean differences
(SMDs) were used for cognitive test scores in RCTs. RESULTS: Of 2,341 potentially
eligible articles, eight studies were included and provided data for 36,196
participants without dementia or cognitive impairment at baseline (mean age 66,
63% female). After adjusting for a median of three potential confounders over a
median follow-up period of 6 years, chronic use of low-dose aspirin was not
associated with onset of dementia or cognitive impairment (5 studies, N = 26,159;
OR = 0.82, 95% CI = 0.55-1.22, P = .33, I2 = 67%). In three RCTs (N = 10,037;
median follow-up 5 years), the use of low-dose aspirin was not associated with
significantly better global cognition (SMD=0.005, 95% CI=-0.04-0.05, P = .84, I2
= 0%) in individuals without dementia. Adherence was lower in participants taking
aspirin than in controls, and the incidence of adverse events was higher.
CONCLUSION: This review found no evidence that low-dose aspirin buffers against
cognitive decline or dementia or improves cognitive test scores in RCTs.
PMID- 28425094
TI - Fatal Acute Hemorrhagic Bowel Infarction Caused by Mesenteric Venous Thrombosis.
AB - Acute mesenteric venous thrombosis (MVT) is a rare, but life-threatening medical
phenomenon. MVT is normally characterized by insidious onset, with nonspecific
signs and symptoms. A high index of clinical suspicion is required for diagnosis,
and emergency surgery is necessary to optimize the chances of patient survival,
especially in the people aged more than 70 years. Surprisingly, based on my
review of the literature, no fatal acute MVT case has been reported in the
forensic literature. All reported such cases have been documented in medical
literature, and most of them have been associated with underlying risk factors
for venous thrombosis, such as hypercoagulable state, certain cancers, and stasis
of the blood flow. Here, I report the case of a sudden unexpected death due to
extensive intestinal ischemia and infarction with massive abdominal hemorrhage
caused by acute MVT in a 72-year-old man without known underlying risk factors.
PMID- 28425095
TI - Psychomotor Tremor and Proprioceptive Control Problems in Current and Former
Stimulant Drug Users: An Accelerometer Study of Heavy Users of Amphetamine, MDMA,
and Other Recreational Stimulants.
AB - The recreational use of various stimulant drugs has been implicated in the
development of movement disorders through dysregulation of the dopaminergic and
serotoninergic neurotransmitter systems. The present study investigated
psychomotor differences in current and former recreational stimulant drug users
compared with nonusing controls. Sixty participants comprised 3 groups: 20
current stimulant drug users (CSUs; 11 men, aged 31.4 +/- 9.1 years), 20 former
stimulant drug users (FSUs; 5 men, aged 39.1 +/- 8.5 years), and 20 nonuser
controls (NUCs; 5 men, aged 35.7 +/- 6.4 years). Psychomotor arm steadiness for
each participant was assessed with a wrist-attached accelerometer during 5 arm
positions with eyes open and then eyes closed. Arm-drop of arm position was
indicated by the arm longitudinal rotation axis (ALoRA), and tremor was indicated
by the overall vector of dynamic body acceleration (VeDBA). Overall, CSUs
performed the most poorly on ALoRA (P < .05) and VeDBA indices (P < .05), and
FSUs perform almost as poorly on VeDBA indices (P < .05) compared with NUCs. It
was concluded that stimulant drug use, primarily MDMA and amphetamines, may
result in acute stimulant-induced tremor as well as long-term proprioceptive
deficits in terms of arm-droop.
PMID- 28425096
TI - Influence of coral cover and structural complexity on the accuracy of visual
surveys of coral-reef fish communities.
AB - Using manipulated patch reefs with combinations of varying live-coral cover (low,
medium and high) and structural complexity (low and high), common community
metrics (abundance, diversity, richness and community composition) collected
through standard underwater visual census techniques were compared with
exhaustive collections using a fish anaesthetic (clove oil). This study showed
that reef condition did not influence underwater visual census estimates at a
community level, but reef condition can influence the detectability of some small
and cryptic species and this may be exacerbated if surveys are conducted on a
larger scale.
PMID- 28425098
TI - Authors' Response.
PMID- 28425099
TI - Network analysis of adhesion/growth-regulatory galectins and their binding sites
in adult chicken retina and choroid.
AB - The highly ordered multilayered organization of the adult chicken retina is a
suitable test model for examining zonal distribution of the members of a
bioeffector family. Based on the concept of the sugar code, the functional
pairing of glycan epitopes with cognate receptors (lectins) is emerging as a
means to explain the control of diverse physiological activities. Having recently
completed the biochemical characterization of all seven adhesion/growth
regulatory galectins present in chicken, it was possible to establish how the
individual characteristics of their expression profiles add up to shape the
galectin network, which until now has not been defined at this level of
complexity. This information will also have relevance in explaining the region
specific presence of glycan determinants in the retina, as illustrated in the
first part of this study using a panel of nine plant/fungal agglutinins. The
following systematic monitoring of the galectins yielded patterns for which
quantitative and qualitative differences were detected. Obviously, positivity in
distinct layers is not confined to a single protein of this family, e.g. CG-1A,
CG-3 or CG-8. These results underline the requirement for network analysis for
these proteins that can functionally interact in additive or antagonistic modes.
Labeling of the tissue galectins facilitated profiling of their accessible
binding sites. It also revealed differences among the galectin family members,
highlighting the ability of this method to define binding properties on the level
of tissue sections. Methodologically, the detection of endogenous lectins
intimates that cognate glycans can become inaccessible, a notable caveat for
lectin histochemical studies.
PMID- 28425097
TI - Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a
mouse model of temporal lobe epilepsy.
AB - Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be
difficult to treat effectively. It can develop after brain injuries that damage
the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal
dentate gyrus have been proposed. This study evaluated a mouse model of temporal
lobe epilepsy to test which pathological changes in the dentate gyrus correlate
with seizure frequency and help prioritize potential mechanisms for further
study. FVB mice (n = 127) that had experienced status epilepticus after systemic
treatment with pilocarpine 31-61 days earlier were video-monitored for
spontaneous, convulsive seizures 9 hr/day every day for 24-36 days. Over 4,060
seizures were observed. Seizure frequency ranged from an average of one every 3.6
days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain,
Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial
fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in
situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods
were used to measure hilar ectopic granule cells, mossy cells, mossy fiber
sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not
significantly correlated with the generation of hilar ectopic granule cells, the
number of mossy cells, the extent of mossy fiber sprouting, the extent of
astrogliosis, or the number of GABAergic interneurons in the molecular layer or
hilus. Seizure frequency significantly correlated with the loss of GABAergic
interneurons in or adjacent to the granule cell layer, but not with the loss of
parvalbumin-positive interneurons. These findings prioritize the loss of granule
cell layer interneurons for further testing as a potential cause of temporal lobe
epilepsy.
PMID- 28425100
TI - Mass spectrometry analysis and in silico prediction of allergenicity of peptides
in tryptic hydrolysates of the proteins from Ruditapes philippinarum.
AB - BACKGROUND: Ruditapes philippinarum is nutrient-rich and widely-distributed, but
little attention has been paid to the identification and characterization of the
bioactive peptides in the bivalve. In the present study, we evaluated the
peptides of the R. philippinarum that were enzymolysised by trypsin using a
combination of ultra-performance liquid chromatography separation and
electrospray ionization quadrupole time-of-flight tandem mass spectrometry,
followed by data processing and sequence-similarity database searching. The
potential allergenicity of the peptides was assessed in silico. RESULTS: The
enzymolysis was performed under the conditions: E:S 3:100 (w/w), pH 9.0, 45
degrees C for 4 h. After separation and detection, the Swiss-Prot database and a
Ruditapes philippinarum sequence database were used: 966 unique peptides were
identified by non-error tolerant database searching; 173 peptides matching 55
precursor proteins comprised highly conserved cytoskeleton proteins. The
remaining 793 peptides were identified from the R. philippinarum sequence
database. The results showed that 510 peptides were labeled as allergens and 31
peptides were potential allergens; 425 peptides were predicted to be
nonallergenic. CONCLUSION: The abundant peptide information contributes to
further investigations of the structure and potential function of R.
philippinarum. Additional in vitro studies are required to demonstrate and ensure
the correct production of the hydrolysates for use in the food industry with
respect to R. philippinarum. (c) 2017 Society of Chemical Industry.
PMID- 28425102
TI - Fatal Overdose of Gamma-hydroxybutyrate Acid After Ingestion of 1,4-Butanediol.
AB - We report a case of fatal intoxication from 1,4-butanediol (1,4-BD), which was
ingested by a young and "naive" gamma-hydroxybutyrate (GHB) consumer during a
party with the co-ingestion of alcohol, cannabis, and methylene-dioxy
methamphetamine. The following drug concentrations were found using gas
chromatography coupled with mass spectrometry on autopsy samples and on a cup and
a glass found at the scene: 20,350 mg/L (bottle) for 1,4-BD; 1020 mg/L (femoral
blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L
(vitreous humor) for GHB. The concentration of GHB is difficult to interpret in
forensic cases due to the possibility of an endogenous production of GHB. The
variable tolerance of the user may also modify the peri- and postmortem GHB
concentrations. This case underscores the need to have many different sources of
toxicology samples analyzed to avoid the hypothesis of endogenous production of
GHB.
PMID- 28425103
TI - Remains of care: opioid substitution treatment in the post-welfare state.
AB - This article examines how the amplified role of pharmaceutical substances in
addiction treatment affects the everyday realisation of care, particularly the
relationship between workers and patients, in so called austere environments.
Theoretically the article draws firstly on the literature that links
pharmaceuticalisation to the neoliberal undoing of central public structures and
institutions of care, and secondly on Anne-Marie Mol's concept of the logic of
care. Based on an ethnographic analysis of the everyday life at a Finnish opioid
substitution treatment clinic we show the mechanisms through which the
realisation of pharmacotherapy can, in the current political climate, result in a
very narrow understanding of drug problems and minimal human contact between
patients and professionals. Our analysis manifests an important shift in the
logic of addiction treatment and health-care policy more broadly; namely, a
growing tendency to emphasise the need for patients to care for themselves and
make good choices with limited help from formal care institutions and
professionals. We call this new ethos the logic of austerity.
PMID- 28425104
TI - Inactivation kinetics and residual activity of CYP3A4 after treatment with
erythromycin.
AB - This study aimed to characterize the inactivation kinetics of cytochrome P450 3A4
(CYP3A4) by erythromycin, which involves mechanism-based inhibition (MBI), in
detail. In addition to an MBI assay based on the conventional method in which
erythromycin and recombinant CYP3A4 were pre-incubated for 15 min, the study also
evaluated the long-term MBI kinetics of this reaction by pre-incubation for 120
min. Mechanism-based inhibition profiles were obtained using three typical
substrates, testosterone, midazolam and nifedipine. In the long-term assay,
erythromycin evoked a time-dependent biphasic reduction in enzyme activity, but
some residual activity (alpha) was detected in the terminal phase. The
inactivation rate constant obtained in the presence of 30 MUm erythromycin using
nifedipine as a substrate was 1.44-fold higher than that acquired using
testosterone, while there was no difference among the alpha values obtained with
the three substrates. In the short-term assay, time-dependent monophasic
inactivation was observed. To extrapolate these data to in vivo, the extent of
the increase in the area under the curve (AUC ratio) induced by erythromycin was
estimated from the results of the conventional short-term experiment and the long
term experiment examining residual activity. The AUC ratio estimated from the
long-term kinetics (2.92) was closer to the clinically reported values (3.3
4.42). In conclusion, the relatively long-term evaluation of the kinetics of
CYP3A4 inactivation revealed that the enzyme was not fully inactivated by
erythromycin. To improve the estimation of the extent of the drug-drug
interactions induced by MBI from in vitro data, longer-term investigations of the
target enzyme's inactivation profile might be necessary.
PMID- 28425105
TI - The incidence of anterior pituitary hormone deficiencies in patients with
microprolactinoma and idiopathic hyperprolactinaemia.
AB - INTRODUCTION: Patients with microprolactinoma and idiopathic hyperprolactinaemia
are not generally considered to be at risk of hypopituitarism and are therefore
not routinely screened for this abnormality. In our clinical practice, we have
observed a number of patients with nonmacroadenomatous hyperprolactinaemia to
have anterior pituitary hormone deficits. AIMS: We aimed to establish the
frequency and clinical significance of anterior pituitary hormone deficiencies,
comparing patients with radiologically proven microprolactinomas and patients
with idiopathic hyperprolactinaemia. STUDY DESIGN: We retrospectively examined
the casenotes of 206 patients with hyperprolactinaemia from our centre. Patients
who did not fit the profile of surgically naive microprolactinoma or idiopathic
hyperprolactinaemia or who had incomplete data were excluded, resulting in a
study group of 56 patients. RESULTS: A total of 35 patients with MRI evidence of
microprolactinoma were identified, three (8.57%) of whom had one or more anterior
pituitary hormone deficiencies. A total of 21 patients with MRI-negative
idiopathic hyperprolactinaemia were identified, nine (42%) of whom had one or
more anterior pituitary hormone deficiencies (P<.01). Only one patient in the MRI
positive group had deficiency that required hormone replacement, in contrast six
patients in the MRI-negative group had deficiencies that were of clinical
significance and which required hormone replacement. SUMMARY: This study shows a
clinically significant incidence of anterior pituitary hormone deficiency in
patients with idiopathic hyperprolactinaemia. The authors recommend that dynamic
pituitary assessment should be considered routinely in this patient group. A
prospective study would be required to assess the underlying cause for these
abnormalities, as they suggest a nontumour pan-pituitary process.
PMID- 28425106
TI - The concept of medicalisation reassessed: a response to Joan Busfield.
PMID- 28425107
TI - Metastatic Urothelial Carcinoma Presenting as Carcinoma Erysipeloides.
PMID- 28425108
TI - Coexistence of psoriasis and epidermolysis bullosa acquisita: Evaluation of the
integrity of the basement membrane.
PMID- 28425109
TI - Alcoholic Cardiomyopathy: Disrupted Protein Balance and Impaired Cardiomyocyte
Contractility.
AB - Alcoholic cardiomyopathy (ACM) can develop after consumption of relatively large
amounts of alcohol over time or from acute binge drinking. Of the many factors
implicated in the etiology of ACM, chronic perturbation in protein balance has
been strongly implicated. This review focused on recent contributions (since
2010) in the area of protein metabolism and cardiac function related to ACM. Data
reviewed include that from in vitro and preclinical in vivo animal studies where
alcohol or an oxidative metabolite was studied and outcome measures in either
cardiomyocytes or whole heart pertaining to protein synthesis or degradation were
reported. Additionally, studies on the contractile properties of cardiomyocytes
were also included to link signal transduction with function. Methodological
differences including the potential impact of sex, dosing, and duration/timing of
alcohol administration are addressed. Acute and chronic alcohol consumption
decreases cardiac protein synthesis and/or activation of proteins within the
regulatory mammalian/mechanistic target of rapamycin complex pathway. Albeit
limited, evidence suggests that myocardial protein degradation via the ubiquitin
pathway is not altered, while autophagy may be enhanced in ACM. Alcohol impairs
ex vivo cardiomyocyte contractility in relation to its metabolism and expression
of proteins within the growth factor pathway. Dysregulation of protein
metabolism, including the rate of protein synthesis and autophagy, may contribute
to contractile deficits and is a hallmark feature of ACM meriting additional sex
inclusive, methodologically consistent studies.
PMID- 28425110
TI - Neural tube defects: Risk factors and preventive measures.
AB - For the last 25 years, it has been proven that the occurrence or recurrence of
neural tube defects can be prevented with the administration of folic acid before
and early pregnancy. At present, over 80 countries in the world, except Japan,
have mandated the fortification of wheat flour and/or rice with folic acid, which
has resulted in a significant reduction in the prevalence of neural tube defects.
In 2000, the Japanese government recommended folic acid 400 MUg daily for young
women of childbearing age and women who are planning to conceive. In 2002, the
government started to present information about the importance of folic acid in
the development of fetuses in the Mother-Child Health Booklet annually. Despite
these endeavors, the prevalence of neural tube defects has remained unchanged. We
discuss the risk factors of neural tube defects and propose preventive measures
to decrease the number of neonates with neural tube defects. We believe that the
government should implement the fortification of staple food with folic acid very
soon, which will eventually decrease not only the neonatal mortality and
morbidity, but also the economic burden on our health care system.
PMID- 28425111
TI - "Nails Only" Phenotype and Partial Dominance of p.Glu170Lys Mutation in a Family
with Epidermolysis Bullosa Simplex.
AB - Epidermolysis bullosa (EB) is a heterogeneous group of rare, chronic, inherited
skin disorders characterized by marked mechanical fragility of epithelial
tissues, with blistering and erosions after minor trauma. We present the first
report of a nails-only phenotype in two patients with epidermolysis bullosa
simplex (EBS) and a heterozygous pGlu170Lys mutation and the second reported case
of EBS associated with a homozygous p.Glu170Lys mutation in the KRT5 gene. Our
findings may be relevant for genetic counseling and for understanding the
inheritance pattern of EBS.
PMID- 28425112
TI - Beyond guidelines: discretionary practice in face-to-face triage nursing.
AB - This article draws on ethnographic data from a Norwegian emergency primary care
clinic (EPCC) to explore nurses' discretionary application of guidelines.
Specifically, it analyses nurses' discretionary use of the Manchester Triage
System (MTS) when performing face-to-face triage, that is, assessing the urgency
of patients' complaints. The analysis shows how nurses assessed patients at odds
with MTS prescriptions by collecting supplementary data, engaging in differential
diagnostic and holistic reasoning, relying on emotion and intuition, and allowing
colleagues and patients to influence their reasoning. The findings also show how
nurses' reasoning led them to override guidelines both overtly and covertly.
Based on this evidence, it is argued that nurses' assessments relied more on
internalised 'triage mindlines' than on codified triage guidelines, although the
MTS did function as a support system, checklist and system for supervisory
control. The study complements existing research on standardisation in nursing by
providing an in-depth analysis of nurses' methods for navigating guidelines and
by detailing how deviations from those guidelines spring from their clinical
reasoning. The challenges of imposing a managerial logic on professional labour
are also highlighted, which is of particular relevance in light of the drive
towards standardisation in modern healthcare.
PMID- 28425113
TI - Environmental perfluorooctane sulfonate exposure drives T cell activation in
bottlenose dolphins.
AB - Perfluoroalkyl acids (PFAAs) are highly stable compounds that have been
associated with immunotoxicity in epidemiologic studies and experimental rodent
models. Lengthy half-lives and resistance to environmental degradation result in
bioaccumulation of PFAAs in humans and wildlife. Perfluorooctane sulfonate
(PFOS), the most prevalent PFAA detected within the environment, is found at high
levels in occupationally exposed humans. We have monitored the environmental
exposure of dolphins in the Charleston, SC region for over 10 years and levels of
PFAAs, and PFOS in particular, were significantly elevated. As dolphins may serve
as large mammal sentinels to identify the impact of environmental chemical
exposure on human disease, we sought to assess the effect of environmental PFAAs
on the cellular immune system in highly exposed dolphins. Herein, we utilized a
novel flow cytometry-based assay to examine T cell-specific responses to
environmental PFAA exposure ex vivo and to exogenous PFOS exposure in vitro.
Baseline PFOS concentrations were associated with significantly increased CD4+
and CD8+ T cell proliferation from a heterogeneous resident dolphin population.
Further analysis demonstrated that in vitro exposure to environmentally relevant
levels of PFOS promoted proinflammatory cytokine production and proliferation in
a dose-dependent manner. Collectively, these findings indicate that PFOS is
capable of inducing proinflammatory interferon-gamma, but not immunoregulatory
interleukin-4 production in T cells, which may establish a state of chronic
immune activation known to be associated with susceptibility to disease. These
findings suggest that PFOS directly dysregulates the dolphin cellular immune
system and has implications for health hazards. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28425114
TI - A multi-institutional joint study of contact dermatitis related to hair colouring
and perming agents in Japan.
AB - BACKGROUND: In Japan, allergic contact dermatitis caused by hair colouring agents
is a considerable problem for those occupationally exposed and also for
consumers. Over the last 20 years, p-phenylenediamine (PPD) has been a common
allergen, with ~7% positive patch test reactions. OBJECTIVES: To investigate
which ingredients caused allergic contact dermatitis related to hair dye and
perming solutions in Japan, to assess whether PPD is suitable for screening for
hair dye allergy, and to propose allergens for a Japanese hairdresser series.
METHODS: We selected 19 hair cosmetic allergens, including PPD, Bandrowski's
base, cysteamine HCl, and ammonium thioglycolate. Altogether 203 patients (26
males and 177 females) with suspected contact allergy to hair colouring or
perming solutions at 14 hospitals in Japan were included. RESULTS: The highest
prevalence of positive reactions (35.1%) was for PPD. p-Methylaminophenol and o
aminophenol were often positive, both in the PPD-positive and in the PPD-negative
patients. Moreover, cysteamine HCl often yielded positive test reactions.
CONCLUSIONS: PPD is insufficient to diagnose contact allergy caused by to hair
dyes. We recommend 13 allergens to be included in a Japanese hairdresser series.
PMID- 28425115
TI - 'It seems like you're going around in circles': recurrent biographical disruption
constructed through the past, present and anticipated future in the narratives of
young adults with inflammatory bowel disease.
AB - Biographical disruption and related concepts continue to be widely drawn upon in
explaining how individuals experience chronic illness. Through in-depth
examination of the narrative experiences of two young adults with inflammatory
bowel disease (IBD), this article aims to contribute to the continuing
theoretical elaboration of biographical disruption, and in turn offer new
insights into how young adults experience this condition. The cases are analysed
from an interaction-based, constructionist perspective, through which it is
argued that the relapse-remission nature of IBD can give rise to a particular
form of recurrent biographical disruption, constructed in narrative through a
complex configuration of past, present and anticipated future experiences. The
two young adults are found to give different meaning to this recurrent disruption
in terms of its significance and consequences - whilst Samuel represents an
ongoing cycle of profound disruption and biographical reinstatement, Edith
normalises the cycle of disruption and its role in her ongoing biography.
Therefore, moving beyond the notion of 'normal illness' observed in previous
research literature, the concept of 'normal recurrent disruption' is proposed.
Finally, it is argued that this recurrent biographical disruption may be
experienced particularly severely in young adulthood owing to the unique
pressures and expectations of this lifestage.
PMID- 28425116
TI - Dynamic probability control limits for risk-adjusted CUSUM charts based on
multiresponses.
AB - For a patient who has survived a surgery, there could be several levels of
recovery. Thus, it is reasonable to consider more than two outcomes when
monitoring surgical outcome quality. The risk-adjusted cumulative sum (CUSUM)
chart based on multiresponses has been developed for monitoring a surgical
process with three or more outcomes. However, there is a significant effect of
varying risk distributions on the in-control performance of the chart when
constant control limits are applied. To overcome this disadvantage, we apply the
dynamic probability control limits to the risk-adjusted CUSUM charts for
multiresponses. The simulation results demonstrate that the in-control
performance of the charts with dynamic probability control limits can be
controlled for different patient populations because these limits are determined
for each specific sequence of patients. Thus, the use of dynamic probability
control limits for risk-adjusted CUSUM charts based on multiresponses allows each
chart to be designed for the corresponding patient sequence of a surgeon or a
hospital and therefore does not require estimating or monitoring the patients'
risk distribution. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425118
TI - Engaging conceptions of identity in a context of medical pluralism: explaining
treatment choices for everyday illness in Niger.
AB - This article uses ethnographic research to reflect upon how the treatment of
'everyday' illnesses in Niger engages concepts of social identity. Inspired by
Bourdieu's concept of social distinction, as well as Appadurai's edited volume on
the 'social lives' of 'things', I present an analysis of how medications are
understood by their users in terms of social and ideological meaning in one rural
Hausa village. Decisions about medication choice were framed by three main
themes: belonging to the 'modern' world, 'traditional' Hausa culture, and
religious identity. This article does not argue that these notions of identity
fully explain medication use, nor necessarily predict treatment choices. The
purpose of this paper is to reflect on the dynamic meanings given to treatment
decisions after they have been made, attributed to the medications themselves and
negotiated through their circulation in a context where multiple medical systems
are drawn from to manage illness. Producers and sellers of medication also engage
these meaning-centred concepts, which have theoretical and practical interest for
the social sciences and public health. A virtual abstract for this paper can be
viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA.
PMID- 28425117
TI - Dream homes and dead ends in the city: a photo essay experiment.
AB - Research focused on the relationship between place and health demonstrates that
it is complex and shifting, as overlapping social, historical, institutional and
political and economic processes continually transform the landscapes in which
lived experiences are embedded. Understanding this relationship requires
knowledge of the situated meanings and local worlds that ethnographic methods are
well suited to investigate. However, even conventional ethnographic methods can
be inadequate to capture the embodied, lived experience of place - experiences in
which the sensory and inner processes of memory and imagination are often
privileged. Accessing these experiences and processes can require more
experimental methodological approaches. In this article, I present work from a
series of photo essays created between 2011 and 2016 by 15 young people who
inhabit the social, spatial and economic margins of Vancouver, Canada, and
discuss some of the challenges and opportunities presented by this methodology.
Created over 5 years, and broadly focused on how they understood, experienced and
navigated their 'place' in the city in the midst of poverty, addiction, violence
and physical and mental health crises, the photo essays young people produced are
embedded with personal biographies and trajectories, as well as shared
experiences of geography, precarity and possibility in Vancouver.
PMID- 28425119
TI - Mean-intercept anisotropy analysis of porous media. I. Analytic formulae for
anisotropic Boolean models.
AB - PURPOSE: Structure-property relations, which relate the shape of the
microstructure to physical properties such as transport or mechanical properties,
need sensitive measures of structure. What are suitable fabric tensors that
quantify the shape of anisotropic heterogeneous materials? The mean intercept
length is among the most commonly used characteristics of anisotropy in porous
media, for example, of trabecular bone in medical physics. METHODS: We analyze
the orientation-biased Boolean model, a versatile stochastic model that
represents microstructures as overlapping grains with an orientation bias towards
a preferred direction. This model is an extension of the isotropic Boolean model,
which has been shown to truthfully reproduce multi-functional properties of
isotropic porous media. We explain the close relationship between the concept of
intersections with test lines to the elaborate mathematical theory of queues, and
how explicit results from the latter can be directly applied to characterize
microstructures. RESULTS: In this series of two papers, we provide analytic
formulas for the anisotropic Boolean model and demonstrate often overlooked
conceptual shortcomings of this approach. Queuing theory is used to derive simple
and illustrative formulas for the mean intercept length. It separates into an
intensity-dependent and an orientation-dependent factor. The global average of
the mean intercept length can be expressed by local characteristics of a single
grain alone. CONCLUSIONS: We thus identify which shape information about the
random process the mean intercept length contains. The connection between global
and local quantities helps to interpret observations and provides insights into
the possibilities and limitations of the analysis. In the second paper of this
series, we discuss, based on the findings in this paper, short-comings of the
mean intercept analysis for (bone-)microstructure characterization. We will
suggest alternative and better defined sensitive anisotropy measures from
integral geometry.
PMID- 28425120
TI - Unravelling Swedish informal caregivers' Generalised Resistance Deficits.
AB - In salutogenic theory, individual/contextual, immaterial/material characteristics
enabling movements towards health are labelled Specific and Generalised
Resistance Resources, SRRs/GRRs, and characteristics counteracting such movements
Specific and Generalised Resistance Deficits, SRDs/GRDs. The aim of this paper
was to present SRDs and GRDs described by caregivers as stemming from themselves
and their care recipient. Guided by salutogenic theory, an explorative design was
used to collect data through interviews with 32 Swedish informal caregivers.
During the theory-driven analysis, SRDs were unravelled using within-case
approaches. To be able to unite them as GRDs across cases, a serviceable GRD
definition was developed from the existing theoretical GRR definition. In
findings, SRDs are visualised in citations and GRDs described in detail.
Caregivers' experiences of SRDs/GRDs are presented as themes: 'Experiencing
personal deficiencies', when stemming from themselves; and 'Struggling with an
uncooperative co-worker', when stemming from their care recipients. Findings
indicate that if these themes dominate a caregiver's view of life, she/he seems
to have reached the 'breaking point' when caregiving ends due to lack of usable
SRRs/GRRs. To prolong the time until this occurs, support, making otherwise
unusable SRRs/GRRs usable, is needed. When designing this type of 'salutogenic'
support, it seems essential to involve the target group (e.g. caregivers, care
recipients), to ascertain what their SRRs/GRRs and SRDs/GRDs may consist of. Such
knowledge regarding SRRs/SRDs could be used to design individualised support, and
regarding GRRs/GRDs to design generalised support at group level. This study
suggests how such new knowledge regarding resistance resources and deficits could
be acquired.
PMID- 28425122
TI - Mean-intercept anisotropy analysis of porous media. II. Conceptual shortcomings
of the MIL tensor definition and Minkowski tensors as an alternative.
AB - PURPOSE: Structure-property relations, which relate the shape of the
microstructure to physical properties such as transport or mechanical properties,
need sensitive measures of structure. What are suitable fabric tensors to
quantify the shape of anisotropic heterogeneous materials? The mean intercept
length is among the most commonly used characteristics of anisotropy in porous
media, e.g., of trabecular bone in medical physics. Yet, in this series of two
papers we demonstrate that it has conceptual shortcomings that limit the validity
of its results. METHODS: We test the validity of general assumptions regarding
the properties of the mean-intercept length tensor using analytical formulas for
the mean-intercept lengths in anisotropic Boolean models (derived in part I of
this series), augmented by numerical simulations. We discuss in detail the
functional form of the mean intercept length as a function of the test line
orientations. RESULTS: As the most prominent result, we find that, at least for
the example of overlapping grains modeling porous media, the polar plot of the
mean intercept length is in general not an ellipse and hence not represented by a
second-rank tensor. This is in stark contrast to the common understanding that
for a large collection of grains the mean intercept length figure averages to an
ellipse. The standard mean intercept length tensor defined by a least-square fit
of an ellipse is based on a model mismatch, which causes an intrinsic lack of
accuracy. CONCLUSIONS: Our analysis reveals several shortcomings of the mean
intercept length tensor analysis that pose conceptual problems and limitations on
the information content of this commonly used analysis method. We suggest the
Minkowski tensors from integral geometry as alternative sensitive measures of
anisotropy. The Minkowski tensors allow for a robust, comprehensive, and
systematic approach to quantify various aspects of structural anisotropy. We show
the Minkowski tensors to be more sensitive, in the sense, that they can quantify
the remnant anisotropy of structures not captured by the mean intercept length
analysis. If applied to porous tissue and microstructures, this improved
structure characterization can yield new insights into the relationships between
geometry and material properties.
PMID- 28425123
TI - A 5-Year Follow-Up of a Cohort of Italian Alcoholics: Hospital Admissions and
Overall Survival.
AB - BACKGROUND: Alcohol use disorders (AUDs), including alcohol dependence and
alcohol abuse defined according to specific DSM-IV and ICD-10 criteria, can be
potentially lethal, because they are associated with several medical and
psychiatric conditions. This study aimed to describe the causes of
hospitalization of a large cohort of subjects with alcohol dependence
(alcoholics) enrolled in Florence (Italy) over a 5-year follow-up period and to
evaluate the effect of hospitalization on overall survival. METHODS: One thousand
one hundred and thirty alcoholics, newly diagnosed from 1997 to 2001, were linked
to the Regional Mortality Registry for update of vital status as of December 31,
2006, and to the Hospital Discharge electronic archives of the Regional Health
System of Tuscany to verify hospital admissions (HAs) during the 5-year
postcohort enrollment follow-up. Kaplan-Meier survival and Cox regression
analyses were performed to evaluate any association of HA with overall survival.
RESULTS: A total of 3,916 new hospitalizations occurred during the 5-year follow
up. Most alcoholics (70.6%) reported at least 1 new hospitalization, with a first
hospitalization rate of 61.7 per 100 person-years in the first year of follow-up.
The mean number of hospitalizations per admitted subject was 4.87 (SD 7.4), and
mean length of hospital stay was 8.5 days (SD 11.3). The main causes of
hospitalization were mental disorders and diseases of the digestive system, as
well as accidents or violence. Among those alcoholics alive after 1 year of
follow-up, a significantly increased risk of dying in the following years could
be predicted by early hospitalization in the 12 months preceding (hazard ratio
[HR] 1.73; 95% confidence interval [CI] 1.15 to 2.60) or following (HR 3.59; 95%
CI 2.31 to 5.61) enrollment in the cohort. CONCLUSIONS: Our results confirm the
association of AUDs with several serious medical conditions. This fact may be
responsible for a high impact on health resource utilization and high social
costs. Early hospitalization significantly predicts vital status at 5 years.
PMID- 28425121
TI - Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational Effects of
Ethanol.
AB - Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor
(KOR) system contribute to various psychiatric disorders, including anxiety,
depression, and addiction. More recently, this endogenous opioid system has
received increased attention as a potential therapeutic target for treating
alcohol use disorders. In this review, we provide an overview and synthesis of
preclinical studies examining the influence of alcohol (ethanol [EtOH]) exposure
on DYN/KOR expression and function, as well as studies examining the effects of
DYN/KOR manipulation on EtOH's rewarding and aversive properties. We then
describe work that has characterized effects of KOR activation and blockade on
EtOH self-administration and EtOH dependence/withdrawal-related behaviors.
Finally, we address how the DYN/KOR system may contribute to stress-EtOH
interactions. Despite an apparent role for the DYN/KOR system in motivational
effects of EtOH, support comes from relatively few studies. Nevertheless, review
of this literature reveals several common themes: (i) rodent strains genetically
predisposed to consume more EtOH generally appear to have reduced DYN/KOR tone in
brain reward circuitry; (ii) acute and chronic EtOH exposure typically up
regulate the DYN/KOR system; (iii) KOR antagonists reduce behavioral indices of
negative affect associated with stress and chronic EtOH exposure/withdrawal; and
(iv) KOR antagonists are effective in reducing EtOH consumption, but are often
more efficacious under conditions that engender high levels of consumption, such
as dependence or stress exposure. These results support the contention that the
DYN/KOR system plays a significant role in contributing to dependence- and stress
induced elevation in EtOH consumption. Overall, more comprehensive analyses (on
both behavioral and mechanistic levels) are needed to provide additional insight
into how the DYN/KOR system is engaged and adapts to influence the motivation
effects of EtOH. This information will be critical for the development of new
pharmacological agents targeting KORs as promising novel therapeutics for alcohol
use disorders and comorbid affective disorders.
PMID- 28425124
TI - Is pyridoxine effective and safe for post-partum lactation inhibition? A
systematic review.
AB - WHAT IS KNOWN AND OBJECTIVE: It has been suggested that pyridoxine has an
antilactogenic effect. Studies of the efficacy of pyridoxine in suppressing
lactation have reported conflicting results. The aim of this review was to
evaluate the effectiveness and safety of high-dose pyridoxine in post-partum
lactation inhibition. METHODS: This systematic review included published trials
that compared the efficacy and/or safety of pyridoxine to placebo or to other
pharmacological agents for the inhibition of post-partum lactation. We searched
PubMed, Embase, ScienceDirect, CINAHL, AMED, the Cochrane library and the
clinical trials registry to identify relevant literature. No limit was imposed on
the year of publication of the studies, and the review included studies published
until 15 January 2016. Two reviewers independently extracted data and assessed
the risk of bias. RESULTS AND DISCUSSION: Seven studies were included, with a
total of 1155 women, of which 471 women received pyridoxine. Three studies were
randomized controlled trials, whereas the remaining four studies were non
randomized controlled trials. All of the included studies were relatively small
(n=18-482). The studies compared pyridoxine with placebo, bromocriptine and/or
stilboestrol. Pyridoxine was given orally, with a total daily dose of 450-600 mg
for 5-7 days. Two trials (n=349 participants) indicated that pyridoxine was
effective in inhibiting lactation in approximately 95% of the enrolled patients.
All other studies failed to demonstrate pyridoxine efficacy through either
clinical assessment or prolactin level measurements. Pyridoxine safety was
assessed by two trials in which no serious untoward side effects were reported.
Overall, the risk of bias for most of the studies was low to moderate. WHAT IS
NEW AND CONCLUSION: Current evidence supporting the effectiveness of high-dose
pyridoxine in the inhibition of post-partum lactation is inconsistent and
insufficient. Larger randomized trials are needed to confirm the efficacy of
pyridoxine in post-partum lactation inhibition.
PMID- 28425125
TI - N-Methyl-4-pyridinium Tetrazolate Zwitterion-Based Photochromic Materials.
AB - N,N'-Disubstituted bipyridinium (viologen) and N-monosubstituted bipyridinium
compounds are well known for their electron-transfer (ET) photochromic behavior.
Their modification has exclusively focused on the N-substituents to date. For the
first time, we have studied the photochromic behavior when one pyridyl ring of
the bipyridinium is substituted with a multifunctional azole group, and have
found that two new coordination compounds based on N-methyl-4-pyridinium
tetrazolate (mptz) zwitterion, [Zn(mptz)2 Br2 ] (1) and [Cd3 (mptz)2 Cl6 ]n ?4n
H2 O (2), exhibit typical ET photochromic behavior owing to photoinduced ET from
halogen anion to the mptz ligand. This work demonstrates a new simple, neutral
photoactive molecule with electron-accepting ability, which may act as a
photoactive component for materials with potential photoswitching and
photocatalysis applications.
PMID- 28425127
TI - Manipulation of glyoxalase pathway confers tolerance to multiple stresses in
rice.
AB - Crop plants face a multitude of diverse abiotic and biotic stresses in the
farmers' fields. Although there now exists a considerable knowledge of the
underlying mechanisms of response to individual stresses, the crosstalk between
response pathways to various abiotic and biotic stresses remains enigmatic. Here,
we investigated if the cytotoxic metabolite methylglyoxal (MG), excess of which
is generated as a common consequence of many abiotic and biotic stresses, may
serve as a key molecule linking responses to diverse stresses. For this, we
generated transgenic rice plants overexpressing the entire two-step glyoxalase
pathway for MG detoxification. Through assessment of various morphological,
physiological and agronomic parameters, we found that glyoxalase-overexpression
imparts tolerance towards abiotic stresses like salinity, drought and heat and
also provides resistance towards damage caused by the sheath blight fungus
(Rhizoctonia solani) toxin phenylacetic acid. We show that the mechanism of
observed tolerance of the glyoxalase-overexpressing plants towards these diverse
abiotic and biotic stresses involves improved MG detoxification and reduced
oxidative damage leading to better protection of chloroplast and mitochondrial
ultrastructure and maintained photosynthetic efficiency under stress conditions.
Together, our findings indicate that MG may serve as a key link between abiotic
and biotic stress response in plants.
PMID- 28425126
TI - Novel sequence variants in the LIPH and LPAR6 genes underlies autosomal recessive
woolly hair/hypotrichosis in consanguineous families.
AB - Autosomal-recessive woolly hair/hypotrichosis (ARWH/H) is a rare genetic disorder
of hair caused by variants in the LIPH and LPAR6 genes. The disease is
characterized by congenital tightly curled hair leading to sparse hair later in
life. In the present report genetic characterization of three consanguineous
families of Pakistani origin, displaying clinical features of ARWH/H, was
performed. Haplotype and DNA sequence analysis of the LIPH gene revealed a novel
homozygous nonsense variant (c.688C > T; p.Gln230*) in family A. In two other
families, B and C, sequence analysis of the LPAR6 gene revealed a novel
homozygous frameshift variant (c.68_69dupGCAT; p.Phe24Hisfs*29) and a previously
reported missense variant (c.188A > T; p.Asp63Val), respectively. Taken together,
our findings will expand the spectrum of variants reported in the LIPH and LPAR6
genes.
PMID- 28425128
TI - Understanding the effects of different social data on selecting priority
conservation areas.
AB - Conservation success is contingent on assessing social and environmental factors
so that cost-effective implementation of strategies and actions can be placed in
a broad social-ecological context. Until now, the focus has been on how to
include spatially explicit social data in conservation planning, whereas the
value of different kinds of social data has received limited attention. In a
regional systematic conservation planning case study in Australia, we examined
the spatial concurrence of a range of spatially explicit social values and land
use preferences collected using a public participation geographic information
system and biological data. We used Zonation to integrate the social data with
the biological data in a series of spatial-prioritization scenarios to determine
the effect of the different types of social data on spatial prioritization
compared with biological data alone. The type of social data (i.e., conservation
opportunities or constraints) significantly affected spatial prioritization
outcomes. The integration of social values and land-use preferences under
different scenarios was highly variable and generated spatial prioritizations 1.2
51% different from those based on biological data alone. The inclusion of
conservation-compatible values and preferences added relatively few new areas to
conservation priorities, whereas including noncompatible economic values and
development preferences as costs significantly changed conservation priority
areas (48.2% and 47.4%, respectively). Based on our results, a multifaceted
conservation prioritization approach that combines spatially explicit social data
with biological data can help conservation planners identify the type of social
data to collect for more effective and feasible conservation actions.
PMID- 28425129
TI - Role of sialyl 6-sulfo Lewis X in antitumor immunity against oral squamous cell
carcinoma.
AB - BACKGROUND: Tumor-infiltrating lymphocytes (TILs) reportedly play a pivotal role
in antitumor immunity against oral squamous cell carcinoma (OSCC); however,
mechanisms governing TIL recruitment to OSCC tissues remain to be clarified. This
study was undertaken to assess a potential association between TILs and high
endothelial venule (HEV)-like vessels that express sialyl 6-sulfo Lewis X (LeX).
METHODS: OSCC tissue sections (n=41) were subjected to immunohistochemistry for
sialyl 6-sulfo LeX and CD34 to allow quantitation of HEV-like vessels. Triple
immunohistochemistry for sialyl 6-sulfo LeX and either CD3 and CD20 or CD4 and
CD8 was conducted to determine which lymphocyte subset is more closely associated
with HEV-like vessels. RESULTS: HEV-like vessels expressing sialyl 6-sulfo LeX
were detected in 27 of 41 (65.9%) OSCC cases, and these vessels were more
frequently found in early disease (T1/T2 stages) compared with advanced (T3/T4)
stages. The number of T cells attached to the inner surface of these HEV-like
vessels was significantly greater than that of B cells, while the number of CD4+
helper T cells and CD8+ cytotoxic T cells did not differ significantly.
Interestingly, sialyl 6-sulfo LeX was also expressed on the membrane of a
fraction of OSCC cells, and CD8+ cytotoxic T cells were almost exclusively found
attached to these carcinoma cells. CONCLUSIONS: Sialyl 6-sulfo LeX is displayed
not only on HEV-like vessels but also on OSCC cells and may potentially function
in antitumor immunity against OSCC.
PMID- 28425131
TI - Garlic Dermatitis on the Neck of an Infant Treated for Nasal Congestion.
AB - The health benefits of garlic (Allium sativum) as a naturopathic remedy have been
well documented, but topical application of garlic has been linked to allergic
and irritant contact dermatitis. We present a case of severe irritant contact
dermatitis due to application of a fresh garlic necklace to the neck of infant
for treatment of nasal congestion.
PMID- 28425130
TI - Histological grading based on poorly differentiated clusters is predictive of
tumour response and clinical outcome in rectal carcinoma treated with neoadjuvant
chemoradiotherapy.
AB - AIMS: The clinical outcome of patients with locally advanced rectal cancer who
undergo neoadjuvant chemoradiotherapy (CRT) is influenced by the tumour response
to treatment, which is reflected by tumour regression grade and post-treatment
(y) TNM stage. Little is known about the prognostic value of pretreatment
histopathological features of the tumour that may be useful to discriminate
potential non-responders and to design tailored therapeutic strategies. In this
study, we aimed to investigate the prognostic role of poorly differentiated
clusters (PDCs) of neoplastic cells in pretreatment biopsies of patients with
rectal cancer treated with neoadjuvant CRT. METHODS AND RESULTS: Grading based on
PDC counting was retrospectively applied to 204 pretreatment endoscopic biopsies
of rectal carcinomas from patients treated with neoadjuvant CRT and surgery.
Interobserver agreement in the assessment of PDC grade was good. High PDC grade
was significantly associated with high yT stage (P = 0.044), yM+ status (P =
0.0004), and unchanged TNM stage or TNM upstaging (P = 0.032). In addition, high
PDC grade was a significant and independent prognostic factor for cancer-specific
survival. CONCLUSIONS: PDC grade may be assessed in preoperative biopsies of
rectal cancer with good reproducibility. High PDC grade in a pretreatment tumour
is significantly associated with a poor response to therapy. Hence, we suggest
that PDC grading might be used as a significant predictive and prognostic factor
in patients with locally advanced rectal cancer who are treated with neoadjuvant
CRT, and to identify high-risk patients who need surgery and adjuvant
chemotherapy.
PMID- 28425132
TI - Early postoperative management after lung transplantation: Results of an
international survey.
AB - INTRODUCTION: Little data exist regarding optimal therapeutic strategies
postoperatively after lung transplant (LTx). Current practice patterns rely on
expert opinion and institutional experience resulting in nonuniform postoperative
care. To better define current practice patterns, an international survey of LTx
clinicians was conducted. METHODS: A 30-question survey was sent to transplant
clinicians via email to the International Society of Heart and Lung
Transplantation open forum mailing list and directly to the chief transplant
surgeon and pulmonologist of all LTx centers in the United States. RESULTS: Fifty
two clinicians representing 10 countries responded to the survey. Sedatives use
patterns included: opiates + propofol (57.2%), opiates + dexmedetomidine (18.4%),
opiates + intermittent benzodiazepines (14.3%), opiates + continuous
benzodiazepines (8.2%), and opiates alone (2%). About 40.4% reported no formal
sedation scale was followed and 13.5% of programs had no formal policy on
sedation and analgesia. A lung protective strategy was commonly employed, with
13.8%, 51.3%, and 35.9% of respondents using tidal volumes of <6 mL/kg ideal body
weight (IBW), 6 mL/kg IBW, and 8 mL/kg IBW, respectively. CONCLUSION: Practice
patterns in the early postoperative care of lung transplant recipients differ
considerably among centers. Many of the reported practices do not conform to
consensus guidelines on management of critically ill patients.
PMID- 28425133
TI - Fecal microbiota signatures of adult patients with different types of short bowel
syndrome.
AB - BACKGROUND AND AIM: Short bowel syndrome (SBS) is a common cause of intestinal
failure and can be divided into three types depending on intestinal anatomy. Gut
dysbiosis has been observed in pediatric SBS patients and is associated with
impaired outcome. Little is known about the changes in gut microbiota of adult
SBS patients. Therefore, we aim to characterize the fecal microbiota of adult
patients with different types of SBS. METHODS: Fifteen fecal samples from healthy
controls and adult patients with type II or type III SBS were collected (five in
each group). Fecal microbial compositions were determined by high-throughput
sequencing, and functional potential was predicted by Phylogenetic Investigation
of Communities by Reconstruction of Unobserved States. RESULTS: Bacterial alpha
diversity significantly decreased in SBS patients and positively correlated to
the remaining small bowel length. SBS II patients were enriched with
Proteobacteria but deficient in Firmicutes and Bacteroidetes. Whereas
Lactobacillus and Prevotella dominated the microbiomes of SBS III patients,
commensal bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae
declined in SBS patients. The parenteral nutrition duration of SBS patients was
positively related to the proportion of Enterobacteriaceae but negatively related
to Lactobacillus. Functional pathways of citrate cycle and branched-chain and
aromatic amino acid biosynthesis were abundant in SBS II patients, while
functional profiles of pyrimidine and purine metabolism were dominant in SBS III
patients. CONCLUSIONS: Short bowel syndrome patients have a marked intestinal
dysbiosis with type II SBS characterized by Proteobacteria and type III SBS
featured by Lactobacillus, resulting in altered functional profiles of fecal
microbiomes.
PMID- 28425134
TI - Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster
Hydroxylation Catalysis.
AB - Tyrosinase model systems pinpoint pathways to translating Nature's synthetic
abilities for useful synthetic catalysts. Mostly, they use N-donor ligands which
mimic the histidine residues coordinating the two copper centres. Copper
complexes with bis(pyrazolyl)methanes with pyridinyl or imidazolyl moieties are
already reported as excellent tyrosinase models. Substitution of the pyridinyl
donor results in the new ligand HC(3-tBuPz)2 (4-CO2 MePy) which stabilises a room
temperature stable MU-eta2 :eta2 -peroxide dicopper(II) species upon oxygenation.
It reveals highly efficient catalytic activity as it hydroxylates 8
hydroxyquinoline in high yields (TONs of up to 20) and much faster than all other
model systems (max. conversion within 7.5 min). Stoichiometric reactions with
para-substituted sodium phenolates show saturation kinetics which are nearly
linear for electron-rich substrates. The resulting Hammett correlation proves the
electrophilic aromatic substitution mechanism. Furthermore, density functional
theory (DFT) calculations elucidate the influence of the substituent at the
pyridinyl donor: the carboxymethyl group adjusts the basicity and nucleophilicity
without additional steric demand. This substitution opens up new pathways in
reactivity tuning.
PMID- 28425135
TI - Image editing for pathologists.
PMID- 28425136
TI - Molecularisation and metaphor.
AB - This article explores the molecularisation of medicine thesis by investigating
reports on genetics and molecular medicine in the New England Journal of
Medicine. While there has indeed been a large increase in the number of
references to molecules in the context of genetics over the last few decades
these are mostly embedded in a framework of explanatory metaphors, namely (gene)
expressivity, penetrance, regulation and pathways. As most of these metaphors are
drawn from the social world it would appear that the molecularisation thesis -
that social life is becoming dominated by the molecular - needs to be tempered by
the ways in which understanding of that molecular world is itself a reflection of
social life.
PMID- 28425137
TI - Three-Dimensional Printing: An Aid to Epidural Access for Neuromodulation.
AB - OBJECTIVE: The case report details to use of three-dimensional (3D) printing as
an aid to neuromodulation. METHODS: A patient is described in whom previous
attempts at spinal neuromodulation had failed due to lack of epidural or
intrathecal access, and the use of a 3D printed model allowed for improved
planning and ultimately, success. RESULTS: Successful spinal cord stimulation was
achieved with the plan developed by access to a 3D model of the patient's spine.
CONCLUSION: Neuromodulation techniques can provide the optimal analgesic
techniques for individual patients. At times these can fail due to lack of access
to the site for intervention, in this case epidural access. 3D printing may
provide additional information to improve the likelihood of access when anatomy
is distorted and standard approaches prove difficult.
PMID- 28425138
TI - Delivering dignified care: A realist synthesis of evidence that promotes
effective listening to and learning from older people's feedback in acute care
settings.
AB - AIMS AND OBJECTIVES: To explore effective mechanisms for listening to and
learning from feedback from older people in the context of acute care.
BACKGROUND: Maintaining the dignity of older people in acute care has become an
issue of international concern. In the United Kingdom, recommendations for care
improvement have led to the formation of an implementation group, the "Listening
and Learning Hospitals Pilot Project." This literature review forms phase 1 of
the project. DESIGN: Realist synthesis was used to explore and synthesise wide
ranging evidence. METHODS: Using 12 databases, literature was scoped to propose
four principles that underpin the context, mechanism and outcomes (CMO) of
effective relation-based interventions with older people and their care partners
in the acute care setting. A search was carried out in order to synthesise data
to refute or support each principle. A total of 137 studies and 11 sources of
grey literature were appraised and included. A final synthesis of evidence across
all principles identified key mechanisms for effective relation-based
interventions. RESULTS: Eight essential mechanisms support effective care
interventions. CONCLUSIONS: This review adds depth and breadth to current nursing
knowledge in this field through the process of realist synthesis. Acute care
organisations need to make a commitment to supporting relational care at
organisation and unit levels. Additionally, they need to value and support the
well-being of the nurses delivering it so that interventions to improve care for
older people can succeed. RELEVANCE TO CLINICAL PRACTICE: Essential mechanisms
synthesised from the review, together with other suggested interventions for
improving dignified care of older people in acute care by listening to them and
learning from their feedback, may contribute towards practice development in
acute care.
PMID- 28425139
TI - Dissecting Cellulitis of the Scalp with Excellent Response to Isotretinoin.
AB - An 18-year-old man presented for evaluation of a 1-year history of painful
nodules on the scalp with associated hair loss. Physical examination revealed
multiple confluent, fluctuant, boggy nodules on the scalp with overlying alopecic
patches. Based on these findings, a diagnosis of dissecting cellulitis of the
scalp was made and the patient was successfully treated with oral isotretinoin
therapy.
PMID- 28425140
TI - Response of parasitoid egg load to host dynamics and implications for egg load
evolution.
AB - A theoretical debate about whether parasitoids should be time or egg limited now
recognizes both as feasible, and interest has turned to determining the
circumstances under which each might arise in the field, and their implications
for parasitoid behaviour and evolution. Egg loads of parasitoids sampled from the
field are predicted to show a negative response to host availability, but
empirical support for this relationship is scarce. We measured how a parasitoid's
egg load responded to seasonal fluctuations in host population density and
recorded the predicted correlation. In early summer, parasitoids were at high
risk of time limitation due to low host availability, and in late summer, their
offspring were at greater risk of egg limitation due to high host availability.
Despite clear seasonal changes in selection pressures on egg load and lifespan,
the parasitoid showed no evidence of seasonal variation in its reproductive
strategy. We made minor modifications to a previously published model to explore
the effects of seasonal variation in host availability on optimal investments in
eggs and lifespan and obtained several new results. In particular, under
circumstances analogous to some of those observed in our field study, temporal
stochasticity in reproductive opportunities can cause investments in eggs to
increase, rather than decrease as previously predicted. Our model results helped
to explain the parasitoid's lack of a seasonally varying reproductive strategy.
Understanding the evolution of parasitoid egg load would benefit from a shift of
research emphasis from purely stochastic variation in parasitoid reproductive
opportunities to greater consideration of host dynamics.
PMID- 28425141
TI - Efficacy of Helicobacter pylori eradication therapies in Korea: A systematic
review and network meta-analysis.
AB - BACKGROUND: The efficacy of Helicobacter pylori eradication regimens may depend
on the country where the studies were performed because of the difference in
antibiotic resistance. We aimed to analyze the efficacy of H. pylori eradication
regimens in Korea where clarithromycin resistance rate is high. METHODS: We
searched for all relevant randomized controlled trials published until November
2016 that investigated the efficacy of H. pylori eradication therapies in Korea.
A network meta-analysis was performed to calculate the direct and indirect
estimates of efficacy among the eradication regimens. RESULTS: Forty-three
studies were identified through a systematic review, of which 34 studies,
published since 2005, were included in the meta-analysis. Among 21 included
regimens, quinolone-containing sequential therapy for 14 days (ST-Q-14) showed
the highest eradication rate (91.4% [95% confidence interval [CI], 86.9%-94.4%]
in the intention-to-treat [ITT] analysis). The eradication rate of the
conventional triple therapy for 7 days, standard sequential therapy for 10 days,
hybrid therapy for 10-14 days, and concomitant therapy for 10-14 days was 71.1%
(95% CI, 68.3%-73.7%), 76.2% (95% CI, 72.8%-79.3%), 79.4% (95% CI, 75.5%-82.8%),
and 78.3% (95% CI, 75.3%-80.9%), respectively, in the ITT analysis. In the
network meta-analysis, ST-Q-14 showed a better comparative efficacy than the
conventional triple therapy, standard sequential therapy, hybrid therapy, and
concomitant therapy. In addition, tolerability of ST-Q-14 was comparable to those
regimens. CONCLUSION: In Korea, ST-Q-14 showed the highest efficacy in terms of
eradication and a comparable tolerability, compared to the results reported for
the conventional triple therapy, standard sequential therapy, hybrid therapy, and
concomitant therapy.
PMID- 28425143
TI - What would Dr. James Parkinson think today? parcelling out the circuitry of
levodopa-induced dyskinesias.
PMID- 28425142
TI - Signaling complexes control the chemotaxis kinase by altering its apparent rate
constant of autophosphorylation.
AB - Autophosphorylating histidine kinase CheA is central to signaling in bacterial
chemotaxis. The kinase donates its phosphoryl group to two response regulators,
CheY that controls flagellar rotation and thus motility and CheB, crucial for
sensory adaptation. As measured by coupled CheY phosphorylation, incorporation
into signaling complexes activates the kinase ~1000-fold and places it under
control of chemoreceptors. By the same assay, receptors modulate kinase activity
~100-fold as a function of receptor ligand occupancy and adaptational
modification. These changes are the essence of chemotactic signaling. Yet, the
enzymatic properties affected by incorporation into signaling complexes, by
chemoreceptor ligand binding or by receptor adaptational modification are largely
undefined. To investigate, we performed steady-state kinetic analysis of
autophosphorylation using a liberated kinase phosphoryl-accepting domain,
characterizing kinase alone, in isolated core signaling complexes and in small
arrays of core complexes assembled in vitro with receptors contained in isolated
native membranes. Autophosphorylation in signaling complexes was measured as a
function of ligand occupancy and adaptational modification. Activation by
incorporation into signaling complexes and modulation in complexes by ligand
occupancy and adaptational modification occurred largely via changes in the
apparent catalytic rate constant (kcat ). Changes in the autophosphorylation kcat
accounted for most of the ~1000-fold kinase activation in signaling complexes
observed for coupled CheY phosphorylation, and the ~100-fold inhibition by ligand
occupancy or modulation by adaptational modification. Our results indicate no
more than a minor role in kinase control for simple sequestration of the
autophosphorylation substrate. Instead they indicate direct effects on the active
site.
PMID- 28425144
TI - Association between endoscopic findings related to colonic diverticula and bowel
habits: A multicenter study in Japan.
AB - BACKGROUND AND AIM: Few studies have shown the associations between colonic
diverticula and endoscopic findings such as location, inflammation, number of
diverticula, sigmoid colon rigidity, and bowel habits. METHODS: Japanese subjects
who underwent total colonoscopies at six centers in Japan from November 2015 to
October 2016 were analyzed. Bowel habits were evaluated using the
Gastrointestinal Symptom Rating Scale. Location and number of diverticula,
inflammation, and sigmoid colon rigidity were evaluated from endoscopy results.
RESULTS: A total of 762 subjects (486 men and 276 women [ratio, 1.76:1]) whose
mean age was 65.5 +/- 11.4 years were evaluated. In multivariate analysis,
presence of constipation was associated with a significantly lower likelihood of
left-sided colonic diverticula (odds ratio = 0.40, 95% confidence interval 0.20
0.82, P = 0.012), whereas right-sided and bilateral-sided colonic diverticula,
multiple colonic diverticula, inflammation findings, and sigmoid colon rigidity
were not related to bowel habits. CONCLUSIONS: Among endoscopic findings related
to colonic diverticula and bowel habits, only left-sided colonic diverticula were
inversely associated with constipation, whereas inflammation findings, multiple
diverticula, and sigmoid colon rigidity were not related to bowel habits.
However, the association of inflammation findings with colonic diverticula and
bowel habits should be further studied. Investigation of changes in left-sided
colonic diverticula may lead to new treatments for constipation.
PMID- 28425145
TI - Prevalence of Gastroesophageal Reflux in Cats During Anesthesia and Effect of
Omeprazole on Gastric pH.
AB - BACKGROUND: Gastroesophageal reflux (GER) is poorly characterized in anesthetized
cats, but can cause aspiration pneumonia, esophagitis, and esophageal stricture
formation. OBJECTIVE: To determine whether pre-anesthetic orally administered
omeprazole increases gastric and esophageal pH and increases serum gastrin
concentrations in anesthetized cats, and to determine the prevalence of GER using
combined multichannel impedance and pH monitoring. ANIMALS: Twenty-seven healthy
cats undergoing elective dental procedures. METHODS: Prospective, double-masked,
placebo-controlled, randomized clinical trial. Cats were randomized to receive 2
PO doses of omeprazole (1.45-2.20 mg/kg) or an empty gelatin capsule placebo 18
24 hours and 4 hours before anesthetic induction. Blood for measurement of serum
gastrin concentration was collected during anesthetic induction. An esophageal
pH/impedance catheter was utilized to continuously measure esophageal pH and
detect GER throughout anesthesia. RESULTS: Mean gastric pH in the cats that
received omeprazole was 7.2 +/- 0.4 (range, 6.6-7.8) and was significantly higher
than the pH in cats that received the placebo 2.8 +/- 1.0 (range, 1.3-4.1; P <
.001). Omeprazole administration was not associated with a significant increase
in serum gastrin concentration (P = .616). Nine of 27 cats (33.3%) had >=1
episode of GER during anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Pre
anesthetic administration of 2 PO doses of omeprazole at a dosage of 1.45-2.20
mg/kg in cats was associated with a significant increase in gastric and
esophageal pH within 24 hours, but was not associated with a significant increase
in serum gastrin concentration. Prevalence of reflux events in cats during
anesthesia was similar to that of dogs during anesthesia.
PMID- 28425147
TI - Liver retransplantation: Recurrent primary sclerosing cholangitis may provide
better outcomes.
PMID- 28425146
TI - A Deep Nasopharyngeal Swab Versus Nonendoscopic Bronchoalveolar Lavage for
Isolation of Bacterial Pathogens from Preweaned Calves With Respiratory Disease.
AB - BACKGROUND: Nonendoscopic bronchoalveolar lavage (BAL) is a practical alternative
for a deep nasopharyngeal swab (DNS) to sample the airways of a large number of
calves in a short period of time. The extent of commensal overgrowth and
agreement of BAL with DNS culture results in preweaned calves are unknown.
OBJECTIVES: To compare commensal overgrowth and bacterial culture results between
DNS and BAL samples. ANIMALS: A total of 183 preweaned calves (144 with bovine
respiratory disease and 39 healthy animals). METHODS: Cross-sectional study. Deep
nasopharyngeal swab and BAL samples were taken from each calf and cultured to
detect Pasteurellaceae and Mycoplasma bovis. Agreement and associations between
culture results of DNS and BAL samples were determined by kappa statistics and
logistic regression. RESULTS: Bronchoalveolar lavage samples were less often
polymicrobial, more frequently negative and yielded more pure cultures compared
to DNS, leading to a clinically interpretable culture result in 79.2% of the
cases compared to only in 31.2% of the DNS samples. Isolation rates were lower in
healthy animals, but not different between DNS and BAL samples. Only Histophilus
somni was more likely to be isolated from BAL samples. In clinical cases, a
polymicrobial DNS culture result did not increase the probability of a
polymicrobial BAL result by >=30%, nor did it influence the probability of a
negative culture. A significant herd effect was noted for all observed
relationships. CONCLUSIONS AND CLINICAL RELEVANCE: Nonendoscopic BAL samples are
far less overgrown by bacteria compared to DNS samples under the conditions of
this study, facilitating clinical interpretation and resulting in a higher return
on investment in bacteriologic culturing.
PMID- 28425148
TI - Counting the publications that count.
PMID- 28425149
TI - Bayes' theorem and the rule of 100: a commentary on 'Validity of administrative
data for identification of obstructive sleep apnea'.
PMID- 28425151
TI - Split liver grafts can benefit both pediatric and adult liver transplant
recipients and programs.
PMID- 28425150
TI - Genetic basis for soma is present in undifferentiated volvocine green algae.
AB - Somatic cellular differentiation plays a critical role in the transition from
unicellular to multicellular life, but the evolution of its genetic basis remains
poorly understood. By definition, somatic cells do not reproduce to pass on genes
and so constitute an extreme form of altruistic behaviour. The volvocine green
algae provide an excellent model system to study the evolution of
multicellularity and somatic differentiation. In Volvox carteri, somatic cell
differentiation is controlled by the regA gene, which is part of a tandem
duplication of genes known as the reg cluster. Although previous work found the
reg cluster in divergent Volvox species, its origin and distribution in the
broader group of volvocine algae has not been known. Here, we show that the reg
cluster is present in many species without somatic cells and determine that the
genetic basis for soma arose before the phenotype at the origin of the family
Volvocaceae approximately 200 million years ago. We hypothesize that the
ancestral function was involved in regulating reproduction in response to stress
and that this function was later co-opted to produce soma. Determining that the
reg cluster was co-opted to control somatic cell development provides insight
into how cellular differentiation, and with it greater levels of complexity and
individuality, evolves.
PMID- 28425152
TI - NMR structures and molecular dynamics simulation of hylin-a1 peptide analogs
interacting with micelles.
AB - Antimicrobial peptides are recognized candidates with pharmaceutical potential
against epidemic emerging multi-drug resistant bacteria. In this study, we use
nuclear magnetic resonance spectroscopy and molecular dynamics simulations to
determine the unknown structure and evaluate the interaction with
dodecylphosphatidylcholine (DPC) and sodium dodecylsulphate (SDS) micelles with
three W6 -Hylin-a1 analogs antimicrobial peptides (HyAc, HyK, and HyD). The HyAc,
HyK, and HyD bound to DPC micelles are all formed by a unique alpha-helix
structure. Moreover, all peptides reach the DPC micelles' core, which thus
suggests that the N-terminal modifications do not influence the interaction with
zwiterionic surfaces. On the other hand, only HyAc and HyK peptides are able to
penetrate the SDS micelle core while HyD remains always at its surface. The
stability of the alpha-helical structure, after peptide-membrane interaction, can
also be important to the second step of peptide insertion into the membrane
hydrophobic core during permeabilization. Copyright (c) 2017 European Peptide
Society and John Wiley & Sons, Ltd.
PMID- 28425153
TI - Nursing students' preferences for clinical placements in the residential aged
care setting.
AB - AIMS AND OBJECTIVES: To examine nursing student placement preferences submitted
as online comments to a university's placement management system, to inform
strategies for positive residential aged care experiences. BACKGROUND: There are
predicted shortages of nurses to service an ageing population. Clinical
placements undertaken by undergraduate nursing students help shape their
attitudes and are a key determinant of career decision-making, yet there is
little research about why students prefer particular placement areas. DESIGN:
Analysis of qualitative data from a placement management system. METHODS: Of
6,610 comments received between 2007-2014, 607 related to aged care and were
coded according to preferences for being placed in a residential aged care
facility, with reasons for this preference thematically coded and quantified.
RESULTS: Four hundred and one comments (66.1%) related to students requesting not
to be allocated residential aged care for the upcoming placement, primarily due
to previous experience in the sector; 104 (17.1%) referred to aged care in a
neutral manner, focusing on conflict of interest; 102 (16.8%) related to a
request for an aged care placement. CONCLUSIONS: The student nurse comments
characterise students as being focused on maximising their learning, while
considering prior experience. In some cases, increased exposure to aged care is
considered to offer limited learning opportunities, which is concerning and
suggests that both the tertiary and aged care sectors have a joint responsibility
to pursue recognition of aged care nursing as a specialised, highly skilled role.
RELEVANCE TO CLINICAL PRACTICE: Nursing programme providers should ensure
curriculum content and exposure to aged care placement clearly identify the
complexities of care and provide genuine opportunities for knowledge acquisition
and skill development based on multifaceted resident care needs. This will
support both those interested in a future aged care career and those undecided.
PMID- 28425154
TI - Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study.
AB - AIM: Gut microbial dysbiosis is implicated in the pathogenesis of non-alcoholic
steatohepatitis (NASH). We investigated downstream effects of gut microbiota
modulation on markers of hepatic inflammation, steatosis, and hepatic and
peripheral insulin sensitivity in patients with NASH using rifaximin therapy.
METHODS: Patients with biopsy-proven NASH and elevated aminotransferase values
were included in this open-label pilot study, all receiving 6 weeks rifaximin 400
mg twice daily, followed by a 6-week observation period. The primary endpoint was
change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary
endpoints were change in hepatic lipid content and insulin sensitivity measured
with a hyperinsulinemic-euglycemic clamp. RESULTS: Fifteen patients (13 men and 2
women) with a median (range) age of 46 (32-63) years were included. Seven had
diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of
therapy, no differences were seen in ALT (55 [33-191] vs. 63 [41-218] IU/L, P =
0.41), peripheral glucose uptake (28.9 [19.4-48.3] to 25.5 [17.7-47.9]
MUmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3-51.7]% vs. 30.0
[10.8-50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2-46.2]% vs. 24.8 [1.7
59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from
baseline, serum ALT increased to 83 (30-217) IU/L, P = 0.02. There was a
significant increase in the homeostasis model assessment-estimated insulin
resistance index (P = 0.05). The urinary metabolic profile indicated a
significant reduction in urinary hippurate with treatment, which reverted to
baseline after cessation of rifaximin, although there was no consistent
difference in relative abundance of fecal microbiota with treatment. CONCLUSION:
These data do not indicate a beneficial effect of rifaximin in patients with
NASH.
PMID- 28425155
TI - Effect of platinum on sintering morphology of porous YSZ ceramics.
AB - Platinum/yttria-stabilized zirconia (Pt/YSZ) porous ceramics were prepared by
sintering of the Pt/PMMA/YSZ stripe-like membrane with a porogen of spherical
polymethyl methacrylate (PMMA) and a precursor of platinum (Pt) of chloroplatinic
acid. The microstructure of raw and processed material and Pt/ZrO2 calcination
process at different sintering temperatures were investigated. The results showed
that the spherically porous structure of Pt/YSZ was observed at a sintering
temperature below 400 degrees C due to the thermal decomposition of PMMA.
However, the pores were shrunk about 35% in diameter when YSZ compacts were
sintered at the temperature of 1,450 degrees C. In addition, the spherical pores
can be retained in the compacts when the content of Pt <5% and then gradually
merged into changing when the content of Pt increased to 50%. The relative
density was increased from 42% to 90% and the open porosity was decreased from
60% to 10% when Pt was added with content from 5% to 80%. The change of
microstructure for Pt/YSZ is due to the migration of Pt and YSZ in the
composites. The preferential migration and coalescence proceeded for Pt in Pt/YSZ
is about 500 degrees C and YSZ clusters can keep stable until up to 900 degrees
C. However, the growth of YSZ particle in the sintering process was hindered by
the scattering of Pt phase.
PMID- 28425156
TI - Universal vs selective ultrasonography to screen for large-for-gestational-age
infants and associated morbidity.
AB - OBJECTIVES: To compare the diagnostic effectiveness of selective vs universal
ultrasonography as a screening test for large-for-gestational-age (LGA) infants,
and to determine whether previously described ultrasound markers of excessive
fetal growth could identify suspected LGA fetuses that are at increased risk of
adverse neonatal outcome. METHODS: Data from the Pregnancy Outcome Prediction
study, a prospective cohort study of nulliparous women with a viable singleton
pregnancy at the time of the dating ultrasound scan, were analyzed. Women were
selected for clinically indicated ultrasound assessment in the third trimester as
per routine clinical care, and the results of these scans were reported
('selective ultrasonography'). In addition, all participants underwent research
ultrasound scans, including estimated fetal weight (EFW) assessment, at around 36
weeks' gestation, in which both the women and their clinicians were blinded to
the results ('universal ultrasonography'). Participants who attended the 36-week
research scan and had a live birth at the Rosie Hospital were included in the
study. Screen positive for LGA was defined as EFW > 90th percentile at >= 34
weeks. RESULTS: The current analysis included 3866 eligible women, of whom 1354
(35%) had a clinically indicated ultrasound scan at or after 34 weeks' gestation.
A total of 177 (4.6%) infants had a birth weight > 90th percentile. The
sensitivity for detection of LGA infants was 27% for selective ultrasonography
and 38% for universal ultrasonography. The specificity of both approaches was
high (99% and 97%, respectively). Using universal ultrasonography, neonatal
outcome differed (P for interaction) by abdominal circumference growth velocity
(ACGV) for both any neonatal morbidity (P = 0.08) and severe adverse neonatal
outcome (P = 0.03). LGA fetuses with increased ACGV had a relative risk of any
neonatal morbidity of 2.0 (95% CI, 1.1-3.6; P = 0.04) and of severe adverse
neonatal outcome of 6.5 (95% CI, 2.0-21.1; P = 0.01), whereas LGA fetuses with
normal ACGV were not at increased risk. CONCLUSIONS: Third-trimester screening of
nulliparous women by universal ultrasound fetal biometry increases the detection
rate of LGA infants and, combined with ACGV, identifies those at increased risk
of adverse neonatal outcome. Copyright (c) 2017 ISUOG. Published by John Wiley &
Sons Ltd.
PMID- 28425157
TI - Geographic variation in mimetic precision among different species of coral snake
mimics.
AB - Batesian mimicry is widespread, but whether and why different species of mimics
vary geographically in resemblance to their model is unclear. We characterized
geographic variation in mimetic precision among four Batesian mimics of coral
snakes. Each mimic occurs where its model is abundant (i.e. in 'deep sympatry'),
rare (i.e. at the sympatry/allopatry boundary or 'edge sympatry') and absent
(i.e. in allopatry). Geographic variation in mimetic precision was qualitatively
different among these mimics. In one mimic, the most precise individuals occurred
in edge sympatry; in another, they occurred in deep sympatry; in the third, they
occurred in allopatry; and in the fourth, precise mimics were not concentrated
anywhere throughout their range. Mimicry was less precise in allopatry than in
sympatry in only two mimics. We present several nonmutually exclusive hypotheses
for these patterns. Generally, examining geographic variation in mimetic
precision - within and among different mimics - offers novel insights into the
causes and consequences of mimicry.
PMID- 28425158
TI - Sexual coloration and sperm performance in the Australian painted dragon lizard,
Ctenophorus pictus.
AB - Theory predicts trade-offs between pre- and post-copulatory sexually selected
traits. This relationship may be mediated by the degree to which males are able
to monopolize access to females, as this will place an upper limit on the
strength of post-copulatory selection. Furthermore, traits that aid in mate
monopolization may be costly to maintain and may limit investment in post
copulatory traits, such as sperm performance. Australian painted dragons are
polymorphic for the presence or absence of a yellow gular patch ('bibs'), which
may aid them to monopolize access to females. Previous work has shown that there
are physiological costs of carrying this bib (greater loss of body condition in
the wild). Here, we show that male painted dragons use this bright yellow bib as
both an inter- and intrasexual signal, and we assess whether this signal is
traded off against sperm performance within the same individuals. We found no
relationship between aspects of bib colour and sperm swimming velocity or
percentage of motile sperm and suggest that the bib polymorphism may be
maintained by complex interactions between physiological or life-history traits
including other sperm or ejaculate traits and environmental influences.
PMID- 28425159
TI - N-terminal diproline and charge group effects on the stabilization of helical
conformation in alanine-based short peptides: CD studies with water and methanol
as solvent.
AB - Protein folding problem remains a formidable challenge as main chain, side chain
and solvent interactions remain entangled and have been difficult to resolve.
Alanine-based short peptides are promising models to dissect protein folding
initiation and propagation structurally as well as energetically. The effect of N
terminal diproline and charged side chains is assessed on the stabilization of
helical conformation in alanine-based short peptides using circular dichroism
(CD) with water and methanol as solvent. A1 (Ac-Pro-Pro-Ala-Lys-Ala-Lys-Ala-Lys
Ala-NH2 ) is designed to assess the effect of N-terminal homochiral diproline and
lysine side chains to induce helical conformation. A2 (Ac-Pro-Pro-Glu-Glu-Ala-Ala
Lys-Lys-Ala-NH2 ) and A3 (Ac-dPro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH2 ) with N
terminal homochiral and heterochiral diproline, respectively, are designed to
assess the effect of Glu...Lys (i, i + 4) salt bridge interactions on the
stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water
manifest different amplitudes of the observed polyproline II (PPII) signals,
which indicate different conformational distributions of the polypeptide
structure. The strong effect of solvent substitution from water to methanol is
observed for the peptides, and CD spectra in methanol evidence A2 and A3 as
helical folds. Temperature-dependent CD spectra of A1 and A2 in water depict an
isodichroic point reflecting coexistence of two conformations, PPII and beta
strand conformation, which is consistent with the previous studies. The results
illuminate the effect of N-terminal diproline and charged side chains in
dictating the preferences for extended-beta, semi-extended PPII and helical
conformation in alanine-based short peptides. The results of the present study
will enhance our understanding on stabilization of helical conformation in short
peptides and hence aid in the design of novel peptides with helical structures.
Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
PMID- 28425160
TI - Causes of nephrotic syndrome and nephrotic-range proteinuria are different in
adult Chinese patients: A single centre study over 33 years.
AB - AIM: The reported causes of nephrotic syndrome (NS) varies between different
countries. Less is known about the causes of nephrotic-range proteinuria (NPU).
We aimed to evaluate the underlying causes of NS and NPU. METHODS: This was a
single-centre, retrospective study of adult patients who underwent renal biopsy
between 1983 and 2015 in a tertiary referral hospital in Hong Kong. We determined
the distribution of histopathological diagnoses with regard to the age subgroups
and time periods. RESULTS: Among 7456 patients who underwent renal biopsy, 982
and 838 patients had NS and NPU, respectively. The most common diagnosis in NS
was minimal change disease (MCD) (33.3%), followed by membranous nephropathy (MN)
(23.6%) and lupus nephritis (LN) (12.8%); whereas the most common diagnosis in
NPU was LN (27.4%), followed by immunoglobulin A nephropathy (IgAN) (21.4%) and
diabetic nephropathy (DN) (9.3%). In the NS group, MCD was the most common
diagnosis in young adults while MN was the leading cause in the elderly. On the
other hand, LN was the most common pathology in the NPU group until the age of
60. Over the past three decades, there was a trend of decrease in the proportion
of IgAN in both NS and NPU group, while a combined pathology of hypertensive
nephrosclerosis and diabetic nephropathy (HTNS and DN) increased significantly.
CONCLUSIONS: The causes of NS and NPU in Chinese adults were different and may
represent two distinct pathological identities. The spectrum of renal
histopathology among these two groups changed significantly over time.
PMID- 28425161
TI - Atorvastatin treatment modulates p16 promoter methylation to regulate p16
expression.
AB - Intimal hyperplasia, the key event of arterial restenosis, is a result of cell
proliferation and cell migration. Atorvastatin exerts an inhibitory effect on
cell proliferation and migration, but the mechanism remains largely unknown. p16,
as a well-known tumor suppressor, was also reported to suppress cell growth and
migration, but with an unclear mechanism. In this study, we demonstrated that
atorvastatin represses cell proliferation and migration in vascular smooth muscle
cells (VSMCs) and that this process is mediated by p16. Furthermore, we found
that DNA methylation in the p16 promoter was reduced and p16 expression was
restored in VSMCs treated with 5-aza-2'-deoxycytidine or atorvastatin. However,
the effect was absent when DNA methyltransferase 1 (DNMT1) was knocked down with
RNA interference. These observations demonstrated that atorvastatin regulates p16
expression via DNMT1-induced DNA methylation in the p16 promoter. In addition, we
found that the mitogen-activated protein kinase (MAPK) pathway was involved in
the regulation of p16 by DNMT1, and MAPK inhibitors partially released the
effects of atorvastatin on p16 and DNMT1. Finally, we illustrated that
atorvastatin inhibits neointima formation and modulates p16 expression in balloon
catheter-injured rat carotid artery. Taken together, we demonstrated that
atorvastatin inhibits neointima formation through inducing p16 expression by
affecting DNA methylation in the p16 promoter region.
PMID- 28425162
TI - A small 'lick' will sink a great ship: fulminant septicaemia after dog saliva
wound treatment in an asplenic patient.
AB - Capnocytophaga canimorsus is a bacterium transmitted through the saliva of dogs.
An infection can cause severe sepsis with acral necrosis and is potentially
fatal. Here, we report the case of a 41-year-old man who was infected through a
wound that was licked by his dog. He went into septic shock with disseminated
intravascular coagulation and subsequently lost both lower legs, his nose and all
the fingers on both hands.
PMID- 28425163
TI - Abstracts of the UROFAIR 2017, Individualised Urological Treatment, 20-22 April
2017, Singapore.
PMID- 28425164
TI - The fallacy of resting echocardiographic parameters of cardiac function in heart
failure with preserved ejection fraction: add global longitudinal strain to the
list.
PMID- 28425165
TI - Melanogenesis-Inhibitory and Cytotoxic Activities of Limonoids, Alkaloids, and
Phenolic Compounds from Phellodendron amurense Bark.
AB - Four limonoids, 1 - 4, five alkaloids, 5 - 9, and four phenolic compounds, 10 -
13, were isolated from a MeOH extract of the bark of Phellodendron amurense
(Rutaceae). Among these, compound 13 was new, and its structure was established
as rel-(1R,2R,3R)-5-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-1
(methoxycarbonylmethyl)indane-2-carboxylic acid methyl ester (gamma-di(methyl
ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1 -
13 against the melanogenesis in the B16 melanoma cells induced with alpha
melanocyte-stimulating hormone (alpha-MSH), four compounds, limonin (1),
noroxyhydrastinine (6), haplopine (7), and 4-methoxy-1-methylquinolin-2(1H)-one
(8), exhibited potent melanogenesis-inhibitory activities with almost no toxicity
to the cells. Western blot analysis revealed that compound 6 inhibited
melanogenesis, at least in part, by inhibiting the expression of protein levels
of tyrosinase, TRP-1, and TRP-2 in alpha-MSH-stimulated B16 melanoma cells. In
addition, when compounds 1 - 13 were evaluated for their cytotoxic activities
against leukemia (HL60), lung (A549), duodenum (AZ521), and breast (SK-BR-3)
cancer cell lines, five compounds, berberine (5), 8, canthin-6-one (9), alpha-di
(methyl ferulate) (12), and 13, exhibited cytotoxicities against one or more
cancer cell lines with IC50 values in the range of 2.6 - 90.0 MUm. In particular,
compound 5 exhibited strong cytotoxicity against AZ521 (IC50 2.6 MUm) which was
superior to that of the reference cisplatin (IC50 9.5 MUm).
PMID- 28425166
TI - Uranyl Photocleavage of Phosphopeptides Yields Truncated C-Terminally Amidated
Peptide Products.
AB - The uranyl ion (UO22+ ) binds phosphopeptides with high affinity, and when
irradiated with UV-light, it can cleave the peptide backbone. In this study, high
accuracy tandem mass spectrometry and enzymatic assays were used to characterise
the photocleavage products resulting from the uranyl photocleavage reaction of a
tetraphosphorylated beta-casein model peptide. We show that the primary
photocleavage products of the uranyl-catalysed reaction are C-terminally
amidated. This could be of great interest to the pharmaceutical industry, as
efficient peptide amidation reactions are one of the top challenges in green
pharmaceutical chemistry.
PMID- 28425167
TI - Continuous subcutaneous insulin infusion: Special needs for children.
AB - Continuous subcutaneous insulin infusion (CSII) is a very common therapy for
children with type 1 diabetes. Due to physiological differences they have other
requirements for their insulin pump than adults. The main difference is the need
for very low basal rates. Even though most available insulin pumps reach a high
accuracy at usual basal rates, accuracy decreases for lower rates. In addition,
the lowest delivered amount at 1 time is limiting the fine tuning of the basal
rate as well as the option for temporary basal rates. Alarms in case of
occlusions depend on accumulation of a certain amount of insulin in the catheter,
and therefore the time until such an alarm is triggered is much longer with lower
basal rates. Accordingly, the risk for hyperglycemia developing into diabetic
ketoacidosis increases. The availability of bolus advisors facilitates the
calculation of meal and correction boluses for children and their parents.
However, there are some differences between the calculators, and the settings
that the calculation is based on are very important. Better connectivity, for
example with a system for continuous glucose monitoring, might help to further
increase safety in the use of CSII in children. When selecting an insulin pump
for a child, the features and characteristics of available pumps should be
properly compared to ensure an effective and safe therapy.
PMID- 28425168
TI - Right ventricular failure after left ventricular assist device implant: 'towards
finding common ground'.
PMID- 28425169
TI - A Highly Active Manganese Catalyst for Enantioselective Ketone and Ester
Hydrogenation.
AB - A new hydrogenation catalyst based on a manganese complex of a chiral P,N,N
ligand has been found to be especially active for the hydrogenation of esters
down to 0.1 mol % catalyst loading, and gives up to 97 % ee in the hydrogenation
of pro-chiral deactivated ketones at 30-50 degrees C.
PMID- 28425170
TI - Brief Report: Rheumatoid Arthritis as the Underlying Cause of Death in Thirty-One
Countries, 1987-2011: Trend Analysis of World Health Organization Mortality
Database.
AB - OBJECTIVE: To examine trends in rheumatoid arthritis (RA) as an underlying cause
of death (UCD) in 31 countries across the world from 1987 to 2011. METHODS: Data
on mortality and population were collected from the World Health Organization
mortality database and from the United Nations Population Prospects database. Age
standardized mortality rates (ASMRs) were calculated by means of direct
standardization. We applied joinpoint regression analysis to identify trends.
Between-country disparities were examined using between-country variance and the
Gini coefficient. Due to low numbers of deaths, we smoothed the ASMRs using a 3
year moving average. Changes in the number of RA deaths between 1987 and 2011
were decomposed using 2 counterfactual scenarios. RESULTS: The absolute number of
deaths with RA registered as the UCD decreased from 9,281 (0.12% of all-cause
deaths) in 1987 to 8,428 (0.09% of all-cause deaths) in 2011. The mean ASMR
decreased from 7.1 million person-years in 1987-1989 to 3.7 million person-years
in 2009-2011 (48.2% reduction). A reduction of >=25% in the ASMR occurred in 21
countries, while a corresponding increase was observed in 3 countries. There was
a persistent reduction in RA mortality, and on average, the ASMR declined by 3.0%
per year. The absolute and relative between-country disparities decreased during
the study period. CONCLUSION: The rates of mortality attributable to RA have
declined globally. However, we observed substantial between-country disparities
in RA mortality, although these disparities decreased over time. Population aging
combined with a decline in RA mortality may lead to an increase in the economic
burden of disease that should be taken into consideration in policy-making.
PMID- 28425171
TI - How is continuity of care experienced by people living with chronic kidney
disease?
AB - AIMS AND OBJECTIVES: To explore patients' perceptions of continuity of care
within a hospital-based specialist service. BACKGROUND: Patient journeys through
health care are becoming increasingly complex. For patients with chronic
conditions, the longevity of their illness and common multiple co-morbidities
make this complexity more pronounced. Continuity of care is most challenging to
provide for these patients. A multifaceted model of continuity is widely
accepted, but despite this, much literature focuses exclusively on relational
aspects. In addition, the majority of the literature has focused on primary and
family care settings whilst continuity within specialist and hospital care has
not been widely researched. DESIGN: A qualitative descriptive design was used.
METHODS: Thirteen semi-structured interviews with patients accessing services as
at a Renal and Transplant Unit at a UK hospital were conducted in 2014. Data were
analysed thematically to identify commonality as well as diversity amongst
participants. RESULTS: Five themes of time, being known, knowledge, knowing the
system and responsibility were identified within patient experiences of
continuity. The multidisciplinary team was more important in relational
continuity than literature has previously suggested. Patients' expectations in
relation to continuity were notably different in their interactions with hospital
based services in comparison with community and family-based care. CONCLUSIONS:
Patients accessing specialist care services may perceive continuity differently
to those receiving care in the community. Generic guidance concerned with patient
experience outcomes may be difficult to implement in practice. RELEVANCE TO
CLINICAL PRACTICE: Nurses and the wider healthcare team play a fundamental role
within the provision of continuity, even in predominantly medically led
specialist services. The differences between primary and secondary care in terms
of patient expectation and experience should be recognised to ensure effective
models of care are implemented which both meet patient expectations and improve
their experience of care.
PMID- 28425172
TI - The homeostatic and circadian sleep recovery responses after total sleep
deprivation in mice.
AB - Many studies on sleep deprivation effects lack data regarding the recovery
period. We investigated the 2-day homeostatic and circadian sleep recovery
response to 24 h of total sleep deprivation (TSD) induced by brief rotation of an
activity wheel. Eight mice were implanted with telemetry transmitters (DSI F40
EET) that recorded simultaneously their electroencephalography (EEG), locomotor
activity and temperature during 24 h of baseline (BSL), TSD and 2 days of
recovery (D1 and D2). In a second experiment, two groups of five non-implanted
mice underwent TSD or ad libitum sleep, after which they were killed, adrenal
glands were weighed and blood was collected for analysis of corticosterone
concentration. During TSD mice were awake at least 97% of the time, with a
consecutive sleep rebound during D1 that persisted during D2. This was
characterized by increases of non-rapid eye movement (NREM) sleep (44.2 +/- 6.9%
for D1 and 43.0 +/- 7.7% for D2 versus 33.8 +/- 9.2% for BSL) and the relative
delta band power (179.2 +/- 34.4% for D1 and 81.9 +/- 11.2% for D2). Greater NREM
and REM sleep amounts were observed during the 'light' periods. Temperature and
locomotor activity characteristics were unchanged during D1 and D2 versus BSL. In
non-implanted mice, corticosterone levels as well as adrenal gland and overall
body weights did not differ between TSD and ad libitum sleep groups. In
conclusion, 24 h of TSD in an activity wheel without stress responses influence
homeostatic sleep regulation with no effect on the circadian regulation over at
least 2 days of recovery in mice.
PMID- 28425173
TI - Twenty-Year Outcome and Association Between Early Treatment and Mortality and
Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results
From the Norfolk Arthritis Register.
AB - OBJECTIVE: To describe the outcome in patients with rheumatoid arthritis (RA)
over 20 years from symptom onset, and to assess the association between early
treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and
disability during follow-up. METHODS: Patients recruited to the Norfolk Arthritis
Register (NOAR) between 1990 and 1994 who met the 2010 American College of
Rheumatology/European League Against Rheumatism RA criteria at baseline were
included in this analysis. Demographic and clinical variables were collected at
baseline and at years 1-3, 5, 7, 10, 15, and 20. Disease activity (swollen joint
count [SJC]/tender joint count [TJC]), disability (Health Assessment
Questionnaire disability index [HAQ DI]), and mortality over 20 years were
determined. Associations between treatment group (early treatment [ET], treatment
<=6 months after symptom onset; late treatment [LT], treatment >6 months after
symptom onset; never treatment [NT], no treatment) and mortality and disability
were assessed using weighted pooled logistic regression and weighted multilevel
mixed-effects linear regression, respectively. Inverse weights were used to
account for confounding by indication and censoring. RESULTS: This study included
602 patients with RA (median age 56 years [interquartile range 44-68 years];
65.9% women). The median SJCs and TJCs were low during the follow-up period (1-3
swollen joints and 3-6 tender joints). The median HAQ DI score increased after
year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk
of mortality was reduced in the ET and LT groups compared with that in the NT
group. The ET group and the NT group had comparable HAQ DI scores during the
follow-up period (beta = 0.03, 95% confidence interval [95% CI] -0.06, 0.12),
while the HAQ DI score was increased in the LT group (for LT versus NT, beta =
0.10 [95% CI 0.02, 0.17]). CONCLUSION: The results of this study indicate the
importance of early treatment with regard to the long-term outcomes in patients
with RA.
PMID- 28425174
TI - Costs and benefits of sublethal Drosophila C virus infection.
AB - Viruses are major evolutionary drivers of insect immune systems. Much of our
knowledge of insect immune responses derives from experimental infections using
the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal
pathogen doses through septic injury, frequently overwhelming host physiology.
While this approach has revealed several immune mechanisms, it is less
informative about the fitness costs hosts may experience during infection in the
wild. Using both systemic and oral infection routes, we find that even apparently
benign, sublethal infections with the horizontally transmitted Drosophila C virus
(DCV) can cause significant physiological and behavioural morbidity that is
relevant for host fitness. We describe DCV-induced effects on fly reproductive
output, digestive health and locomotor activity, and we find that viral morbidity
varies according to the concentration of pathogen inoculum, host genetic
background and sex. Notably, sublethal DCV infection resulted in a significant
increase in fly reproduction, but this effect depended on host genotype. We
discuss the relevance of sublethal morbidity for Drosophila ecology and
evolution, and more broadly, we remark on the implications of deleterious and
beneficial infections for the evolution of insect immunity.
PMID- 28425175
TI - Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which
disrupts cell-cell adhesions in vitro and induces haemorrhage in vivo.
AB - Snake venom metalloproteases (SVMPs) are members of the a disintegrin and
metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs
are known to elicit snake venom-induced haemorrhage; however, the target proteins
and cleavage sites are not known. In this work, we identified a target protein of
vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to
induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin
and gamma-catenin from the cell-cell junction to the cytosol, without inducing
proteolysis of VE-cadherin. The Wnt receptors low-density lipoprotein receptor
related proteins 5 and 6 (LRP5/6) are known to promote catenin relocation, and
are rendered constitutively active in Wnt signalling by truncation. Thus, we
examined whether VAP1 cleaves LRP5/6 to induce catenin relocation. Indeed, we
found that VAP1 cleaved the extracellular region of LRP6 and LRP5. This cleavage
removes four inhibitory beta-propeller structures, resulting in activation of
LRP5/6. Recombinant human ADAM8 and ADAM12 also cleaved LRP6 at the same site. An
antibody against a peptide including the LRP6-cleavage site inhibited VAP1
induced VE-cadherin relocation and disruption of cell-cell adhesions in cultured
cells, and blocked haemorrhage in mice in vivo. Intriguingly, animals resistant
to the effects of haemorrhagic snake venom express variants of LRP5/6 that lack
the VAP1-cleavage site, or low-density lipoprotein receptor domain class A
domains involved in formation of the constitutively active form. The results
validate LRP5/6 as physiological targets of ADAMs. Furthermore, they indicate
that SVMP-induced cleavage of LRP5/6 causes disruption of cell-cell adhesion and
haemorrhage, potentially opening new avenues for the treatment of snake bites.
PMID- 28425176
TI - Polyhydroxyalkanoate-associated phasins as phylogenetically heterogeneous,
multipurpose proteins.
AB - Polyhydroxyalkanoates (PHAs) are natural polyesters of increasing
biotechnological importance that are synthesized by many prokaryotic organisms as
carbon and energy storage compounds in limiting growth conditions. PHAs
accumulate intracellularly in form of inclusion bodies that are covered with a
proteinaceous surface layer (granule-associated proteins or GAPs) conforming a
network-like surface of structural, metabolic and regulatory polypeptides, and
configuring the PHA granules as complex and well-organized subcellular structures
that have been designated as 'carbonosomes'. GAPs include several enzymes related
to PHA metabolism (synthases, depolymerases and hydroxylases) together with the
so-called phasins, an heterogeneous group of small-size proteins that cover most
of the PHA granule and that are devoid of catalytic functions but nevertheless
play an essential role in granule structure and PHA metabolism. Structurally,
phasins are amphiphilic proteins that shield the hydrophobic polymer from the
cytoplasm. Here, we summarize the characteristics of the different phasins
identified so far from PHA producer organisms and highlight the diverse
opportunities that they offer in the Biotechnology field.
PMID- 28425177
TI - Design and Synthesis of C3-Substituted beta-Carboline-Based Histone Deacetylase
Inhibitors with Potent Antitumor Activities.
AB - A series of hydroxamic acid histone deacetylase (HDAC) inhibitors in which the
beta-carboline motif has been incorporated were designed and synthesized. The
effect of substitution at the C3 amide on HDAC inhibition and antiproliferative
activities was investigated. Most of these compounds were found to display
significant HDAC inhibitory effects and good antiproliferative activity, with
IC50 values in the low-micromolar range. In particular, the HDAC inhibition IC50
value of N-(2-(dimethylamino)ethyl)-N-(4-(hydroxylcarbamoyl)benzyl)-1-(4
methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (9 h) is five-fold lower than
that of suberoylanilide hydroxamic acid (SAHA, vorinostat). Furthermore, 9 h was
found to increase the acetylation of histone H3 and alpha-tubulin, and to induce
DNA damage as evidenced by hypochromism and enhanced phosphorylation of histone
H2AX. Compound 9 h inhibits Stat3, Akt, and ERK signaling, important cell-growth
promoting pathways that are aberrantly activated in most cancers. Finally, 9 h
showed reasonable solubility and permeability in Caco-2 cells. Our findings
suggest that these novel beta-carboline-based HDAC inhibitors may hold great
promise as therapeutic agents for the treatment of human cancers.
PMID- 28425178
TI - Sleep quality, clinical and psychological manifestations in women with systemic
lupus erythematosus.
AB - AIM: Sleep problems are a common complaint in systemic lupus erythematosus (SLE)
patients. We analyzed sleep quality with subjective and objective measures in a
sample with SLE and its possible relationships with the main manifestations of
the disease. METHODS: Twenty-one women with SLE and 20 healthy women participated
in the study. All participants were evaluated with actigraphy for a week and they
completed self-report instruments of sleep quality, quality of life, fatigue,
anxiety, depression and perceived stress. Comparison analyses between the two
groups were done using Chi-square and Student's t-tests. The association between
sleep quality and the remaining variables was explored using Pearson correlation
coefficients. RESULTS: SLE patients had higher fragmentation index in the
actigraphic analysis and a perception of poorer sleep quality, more fatigue,
anxiety and depression than the control group. Bivariate analyses showed that the
perception of more sleep disturbance and daytime dysfunction was associated with
a lower health-related quality of life, more fatigue, emotional discomfort and
more perceived stress. Also, the fragmentation index in the actigraphy was
significantly related to the perception of poorer quality of sleep. CONCLUSION:
SLE women had a poorer sleep quality (objective and subjective). These
alterations could play a modulatory role in clinical and psychological
manifestations of the disease and affect the quality of life in this population.
More research is needed to clarify these relations and to determine the potential
benefits of interventions directed to improve sleep in the clinical managing of
the patients with SLE.
PMID- 28425180
TI - American College of Cardiology 2017.
PMID- 28425179
TI - Resilience of the prokaryotic microbial community of Acropora digitifera to
elevated temperature.
AB - The coral is a holobiont formed by the close interaction between the coral animal
and a diverse community of microorganisms, including dinoflagellates, bacteria,
archaea, fungi, and viruses. The prokaryotic symbionts of corals are important
for host fitness but are also highly sensitive to changes in the environment. In
this study, we used 16S ribosomal RNA (rRNA) sequencing to examine the response
of the microbial community associated with the coral, Acropora digitifera, to
elevated temperature. The A. digitifera microbial community is dominated by
operational taxonomic unit (OTUs) affiliated with classes Alphaproteobacteria and
Gammaproteobacteria. The prokaryotic community in the coral tissue is distinct
from that of the mucus and the surrounding seawater. Remarkably, the overall
microbial community structure of A. digitifera remained stable for 10 days of
continuous exptosure at 32 degrees C compared to corals maintained at 27 degrees
C. However, the elevated temperature regime resulted in a decrease in the
abundance of OTUs affiliated with certain groups of bacteria, such as order
Rhodobacterales. On the other hand, some OTUs affiliated with the orders
Alteromonadales, Vibrionales, and Flavobacteriales, which are often associated
with diseased and stressed corals, increased in abundance. Thus, while the A.
digitifera bacterial community structure appears resilient to higher temperature,
prolonged exposure and intensified stress results in changes in the abundance of
specific microbial community members that may affect the overall metabolic state
and health of the coral holobiont.
PMID- 28425181
TI - Effects of different aerobic exercise frequencies on streptozotocin-nicotinamide
induced type 2 diabetic rats: Continuous versus short bouts and weekend warrior
exercises.
AB - BACKGROUND: Exercise training is known to have multiple beneficial effects on
type 2 diabetes mellitus (T2DM). The aim of this study was to explore the effects
of aerobic exercise frequency on diabetic parameters, the histopathological
structure of skeletal muscle, diabetic myopathy, and mitochondrial enzyme
activity in an experimental model of T2DM. METHODS: Sprague-Dawley rats (n = 35)
were rendered diabetic by injection of nicotinamide (110 mg/kg) and
streptozotocin (65 mg/kg). Rats with blood glucose concentrations between 7 and
17 mmol/L were used. Diabetic rats were randomly allocated to one of the
following groups: (i) control sedentary; (ii) diabetic sedentary; (iii) diabetic
with continuous exercise (30 min/day, 5 days/week); (iv) diabetic with short
bouts of exercise (3 * 10 min/day, 5 days/week); and (v) diabetic rats as
"weekend warriors" (35 + 40 min/day, 2 days/week). After 6 weeks swimming
exercise (total duration 150 min/week), biochemical tests were performed to
measure insulin, glucose, cytokines, serum and muscle myeloperoxidase (MPO), and
malondialdehyde (MDA) levels. Histologic analysis (histomorphometric and
mitochondrial enzyme analysis) was also performed. RESULTS: Compared with
diabetic sedentary rats, significant improvements were observed in all exercise
groups in terms of glucose levels, weight loss, tissue MPO and MDA levels,
muscular connective tissue, muscle atrophy, mitochondrial enzyme, and all
histomorphometric analyses. CONCLUSIONS: The results of the study emphasize the
effects of training on inflammation, increased oxidative stress, myopathy, and
mitochondrial damage in a rat model of T2DM, and demonstrate that there is no
major difference between exercise modalities provided that the total duration of
exercise remains the same.
PMID- 28425182
TI - Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a
systematic review.
AB - The aim of this review was to understand the landscape of serum ferritin in
diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron
deficiency in pregnancy is a major public health problem leading to the
development of anaemia. Reducing the global prevalence of anaemia in women of
reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the
gold standard test for iron deficiency but requires an invasive procedure;
therefore, serum ferritin is the most clinically useful test. We undertook a
systematic search of electronic databases and trial registers from inception to
January 2016. Studies of iron or micronutrient supplementation in pregnancy with
pre-defined serum ferritin thresholds were included. Two independent reviewers
selected studies, extracted data and assessed quality. There were 76 relevant
studies mainly of observational study design (57%). The most commonly used
thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and
<15 ng mL-1 (68%). Most primary studies provided no justification for the choice
of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by
expert consensus in a guideline development process. There were five studies (7%)
using a serum ferritin threshold defining iron deficiency derived from primary
studies of bone marrow aspiration. Unified international thresholds of iron
deficiency for women throughout pregnancy are required for accurate assessments
of the global disease burden and for evaluating effectiveness of interventions
addressing this problem.
PMID- 28425184
TI - Enantioselective Synthesis of (+)-Mitomycin K by a Palladium-Catalyzed Oxidative
Tandem Cyclization.
AB - The mitomycins, a family of bioactive natural products, feature a compact 6/5/5
fused polycyclic ring structure densely decorated with highly reactive and/or
fragile quinone, amino ketal, and aziridine as well as carbamate moieties. It is
this striking feature that has defeated numerous synthetic attempts towards these
apparently small molecules, rendering them one of the most formidable targets for
total synthesis. We herein report the first enantioselective synthesis of (+)
mitomycin K, a representative of G series mitomycins. The key step of this
synthesis is an enantioselective oxidative cyclization catalyzed by a
palladium/(+)-sparteine system that had previously been developed by our group.
The robustness of this method bodes well for further applications in the
asymmetric total synthesis of natural products, particularly those with
characteristic 6/5/5-fused pyrroloindole skeletons.
PMID- 28425183
TI - Associations between major life events and adherence, glycemic control, and
psychosocial characteristics in teens with type 1 diabetes.
AB - AIMS: This cross-sectional study assessed the type of major life events occurring
in a contemporary sample of teens with type 1 diabetes and the association
between event frequency and demographic, diabetes management, and psychosocial
characteristics. METHODS: Parents of 178 teens completed the Life Events
Checklist to report major events teens had experienced in the last year: 42%
experienced 0 to 1 event (n = 75), 32% experienced 2 to 3 events (n = 57), and
26% experienced 4+ events (n = 46). Teens and parents completed validated
measures of treatment adherence, diabetes-specific self-efficacy, quality of
life, and diabetes-specific family conflict. Parent-youth interview and chart
review provided demographics and diabetes management data. RESULTS: Mean number
of events/teen was 2.6 +/- 2.7 (range = 0-15). The most common events were
"Hospitalization of a family member" (24%), "Getting a bad report card" (20%),
"Serious arguments between parents" (19%), and "Serious illness/injury in a
family member" (19%). Compared with teens experiencing 0 to 1 event, teens
experiencing 4+ events were less likely to have married parents (P = .01) and a
parent with a college degree (P = .006). Teens with 4+ events had significantly
poorer adherence (P = .002 teen, P = .02 parent), lower self-efficacy (P = .03
teen, P < .0001 parent), poorer quality of life (P < .0001 teen, P < .0001
parent), and more conflict (P = .006 teen, P = .02 parent) than teens with fewer
events. In a multivariate model (R 2 = 0.21, P < .0001) controlling for
demographic and diabetes management characteristics, fewer events was associated
with lower A1c (P = .0009). CONCLUSIONS: Occurrence of more major life events was
associated with poorer diabetes care and A1c and more negative psychosocial
qualities in teens with type 1 diabetes.
PMID- 28425185
TI - The influence of hippocampal atrophy on the cognitive phenotype of dementia with
Lewy bodies.
AB - OBJECTIVE: The level of hippocampal atrophy in dementia with Lewy bodies (DLB) is
typically less than that observed in Alzheimer's disease (AD). However, it is not
known how the cognitive phenotype of DLB is influenced by hippocampal atrophy or
the atrophy of adjacent medial temporal lobe structures. METHODS: Dementia with
Lewy bodies (n = 65), AD (n = 76) and control (n = 63) participants underwent 3T
magnetic resonance imaging and cognitive Cambridge Cognitive Examination and Mini
Mental State Examination (CAMCOG and MMSE) assessments. Hippocampal volume, and
parahippocampal, entorhinal and temporal pole cortical thickness, was compared
between groups. Regression models were used to investigate whether hippocampal
volume and cortical thickness associated with global cognition and cognitive
subdomains. RESULTS: Dementia with Lewy bodies, AD and control participants
showed significantly different hippocampal, parahippocampal and entorhinal
cortical thinning, where atrophy was greatest in AD and intermediate in DLB.
Temporal pole thickness was reduced in DLB and AD compared with control
participants. In DLB, but not AD, hippocampal volume associated with total
CAMCOG, CAMCOG memory and MMSE scores. In DLB, parahippocampal, entorhinal and
temporal pole thickness associated with total CAMCOG and CAMCOG memory scores,
parahippocampal thickness associated with MMSE scores, and entorhinal thickness
associated with CAMCOG executive function scores. CONCLUSIONS: In this large
sample, these results are in agreement with other studies indicating that
hippocampal atrophy is less severe in DLB than AD. Hippocampal atrophy and medial
temporal lobe cortical thickness were associated with the severity of cognitive
symptoms, suggesting that atrophy in these structures, as a potential proxy of AD
pathology, may partly mediate specific DLB cognitive symptoms. (c) 2017 The
Authors. International Journal of Geriatric Psychiatry Published by John Wiley &
Sons Ltd.
PMID- 28425188
TI - Effects of age and viscosity on food transport and breathing-swallowing
coordination during eating of two-phase food in nursing home residents.
AB - AIM: When eating food that contains both liquid and solid phases, the liquid
component frequently enters the hypopharynx before swallowing and can increase
the risk of aspiration. Thus, we examined whether the initial viscosity of mixed
consistency food could alter pre-swallow food transport and breathing-swallowing
coordination in older adults. METHODS: Fiberoptic endoscopy was recorded while 18
healthy young adults and 19 older adults ate 5 g of steamed rice combined with 3
mL of blue-dye water. Liquid viscosity was set at three levels by the addition of
a thickening agent (0 wt%, thin; 2 wt%, thicker; 4 wt%, higher-viscosity,
respectively). We measured the timing of swallow initiation and its corresponding
respiratory phase for each participant. RESULTS: For thin mixed consistency food,
whereas the timing of swallow initiation was comparable between young and older
participants, swallowing was initiated during inspiration significantly more
often in older participants (31.6 %) than in young participants (5.6 %). In
contrast, the timing of swallow initiation was delayed in older participants for
thicker and higher-viscosity foods, although swallowing was commonly initiated
during expiration in both groups. CONCLUSIONS: In older adults, we observed that
swallow initiation function was preserved for thin mixed consistency samples, but
breathing-swallowing coupling was diminished. For higher-viscosity foods, swallow
initiation was delayed in this group, but breathing-swallowing coordination was
not disturbed, probably as a result of the slow bolus flow into the hypopharynx.
Thus, it appears the initial viscosity of mixed consistency food profoundly
affects food transport before swallowing as well as breathing-swallowing
coordination in nursing home residents. Geriatr Gerontol Int 2017; 17: 2171-2177.
PMID- 28425187
TI - Significance of measured intraoperative portal vein flows after
thrombendvenectomy in deceased donor liver transplantations with portal vein
thrombosis.
AB - Adequate portal vein (PV) flow in liver transplantation is essential for a good
outcome, and it may be compromised in patients with portal vein thrombosis (PVT).
This study evaluated the impact of intraoperatively measured PV flow after PV
thrombendvenectomy on outcomes after deceased donor liver transplantation (DDLT).
The study included 77 patients over a 16-year period who underwent PV
thrombendvenectomy with complete flow data. Patients were classified into 2
groups: high PV flow (>1300 mL/minute; n = 55) and low PV flow (<=1300 mL/minute;
n = 22). Postoperative complications and graft survival were analyzed according
to the PV flow. The 2 groups were similar in demographic characteristics. Low PV
flow was associated with higher cumulative rates of biliary strictures (P = 0.02)
and lower 1-, 2-, and 5-year graft survival (89%, 85%, and 68% versus 64%, 55%,
and 38%, respectively; P = 0.002). There was no difference in the incidence of
postoperative PVT between the groups (1.8% versus 9.1%; P = 0.19). No biliary
leaks or hepatic artery thromboses were reported in either group. By multivariate
analyses, age >60 years (hazard ratio [HR], 3.04, 95% confidence interval [CI],
1.36-6.82; P = 0.007) and low portal flow (HR, 2.31; 95% CI, 1.15-4.65; P = 0.02)
were associated with worse survival. In conclusion, PV flow <1300 mL/minute after
PV thrombendvenectomy for PVT during DDLT was associated with higher rates of
biliary strictures and worse graft survival. Consideration should be given to
identifying reasons for low flow and performing maneuvers to increase PV flow
when intraoperative PV flows are <1300 mL/minute. Liver Transplantation 23 1032
1039 2017 AASLD.
PMID- 28425186
TI - Association studies of low-frequency coding variants in nonsyndromic cleft lip
with or without cleft palate.
AB - Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common
human birth defects with complex etiology. Although genome-wide association
studies have successfully identified a number of risk loci, these loci only
account for about 20% of the heritability of orofacial clefts. The "missing"
heritability may be found in rare variants, copy number variants, or
interactions. In this study, we investigated the role of low-frequency variants
genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip.
We performed two statistical tests, Sequence Kernel Association Test (SKAT) and
Combined Multivariate and Collapsing (CMC) method using two minor allele
frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding
variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of
NSCL/P. Low-frequency variants in other genes were associated with decreased risk
of NSCL/P. These results demonstrate that low-frequency variants contribute to
the genetic etiology of NSCL/P.
PMID- 28425189
TI - The Global Ethics Corner: foundations, beliefs, and the teaching of biomedical
and scientific ethics around the world.
AB - The profound advances in the biomolecular sciences over the last decades have
enabled similar advances in biomedicine. These advances have increasingly
challenged our abilities to deploy them in an equitable and ethically acceptable
manner. As such, it has become necessary and important to teach biomedical and
scientific ethics to our students who will become the researchers, medical
professionals, and global citizens of the future. As advances in the biosciences
and medicine are made, developed, and used across the globe, our survival on an
endangered planet requires global dialog and consensual action. To that end, a
group of us from around the world have come together to describe the differing
foundations of our ethical beliefs, and how ethical issues in biomedicine and in
science are described and confronted in our countries. We hope to show the
commonality in our beliefs and practices and to encourage readers from around the
world to contribute to a continuing discussion through a new section of the
journal, The Global Ethics Corner. (c) 2017 by The International Union of
Biochemistry and Molecular Biology, 45(5):385-395, 2017.
PMID- 28425190
TI - Identification of the novel HLA-B*27:147 allele by polymerase chain reaction
sequence-based typing.
AB - HLA-B*27:147 differs from HLA-B*27:04:01 by a single nucleotide substitution at
position 523 C>G.
PMID- 28425191
TI - Thank god it's Friday - sleep improved.
AB - The weekend is usually seen as a window of recovery. Thus, sleep before a day off
may be less impaired than that before a workday. However, very few
polysomnographical studies have investigated this hypothesis. Therefore, the aim
of the present study was to compare sleep before a workday with that before a
weekend. Seventeen teachers participated. Sleep was recorded with polysomnography
on one weekday night during the workweek, and on a workday (Friday) followed by a
day off. Sleep diaries and actigraphs were also used. Weekend sleep showed
delayed bedtime and time of rising, a longer total sleep time (45 min), increased
N3 and N1, and decreased N2 and REM. Sleep spindles were reduced. The results
remained after truncation to the shortest common sleep duration (5 h). The
increase in N3 from weekday sleep to Friday night sleep was positively correlated
with N1 change (r = 0.853, P <= 0.001), and negatively correlated with N2 change
(r = -0.614, P <= 0.001). Subjective ratings showed that weekend sleep was
associated with less awakening problems and lower subjective arousal during the
day. The authors concluded that weekend sleep was longer, and showed increased N3
and N1. The authors suggest that the N3 increase before the day off is a result
of lower stress, while the N1 increase may be an effect of sleep spindle
suppression via the increase of N3 (which would suppress sleep spindles), thus
reducing N2 and enhancing N1.
PMID- 28425192
TI - Soluble-HLA-E: A follow up biomarker in Takayasu arteritis, independent of HLA-E
genotype.
AB - AIM: Disease activity assessment in Takayasu arteritis (TA) is challenging. Human
leukocyte antigen E (HLA-E) is shed from endothelium into serum as a soluble
molecule (sHLA-E) in response to inflammation. We aimed to study: (i) utility of
sHLA-E as a biomarker of disease activity; and (ii) association of HLA-E
polymorphism rs1264457 with clinical disease in Asian-Indian TA patients.
MATERIALS AND METHODS: In phase-1, sHLA-E levels were estimated in sera of 50
consecutive TA patients at baseline visit and 27 healthy controls. Serial
estimations were performed in 27 of them. In phase-2, DNA of 150 TA patients and
264 healthy controls were genotyped for rs1264457 polymorphism. RESULTS: At
baseline visit, disease was classified as active, stable and grumbling in 23, 18
and nine patients, respectively. sHLA-E levels were higher in active TA (43;
interquartile range [IQR]: 25.3-64.6) pg/mL) than stable disease (12.9; IQR: 7.6
21.6 pg/mL) (P = 0.001). At first follow-up visit, sHLA-E levels were numerically
higher in active disease than stable disease (P = 0.06) but this trend was
blunted at second follow-up. sHLA-E levels increased in 54% versus 25% of
patients with persistently active/relapsing and persistent stable course,
respectively. rs1264457 polymorphism was not associated with susceptibility to TA
and did not affect sHLA-E levels. CONCLUSION: sHLA-E level is useful as a
biomarker of disease activity and course in TA patients. rs1264457 polymorphism
is neither associated with susceptibility nor did it influence sHLA-E levels in
TA.
PMID- 28425193
TI - Health-related quality of life outcomes from a contemporary prostate cancer
registry in a large diverse population.
AB - OBJECTIVE: To assess the health-related quality of life (HRQoL) of patients with
prostate cancer up to 24 months after treatment in a contemporary large diverse
population. PATIENTS AND METHODS: Patients with newly diagnosed prostate cancer
from March 2011 to January 2014 in our healthcare system were included. The
Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was administered
before treatment, and at 1, 3, 6, 12, 18, and 24 months after treatment up to
November 2014 for all methods of treatment. The Kruskall-Wallis test was used to
compare the distribution of each EPIC-26 domain score at each time point, and
mixed models were used to assess the overall scores over the period after
treatment. RESULTS: In all, 5 727 patients were included. There were data for 3
422, 2 329, 2 017, 1 922, 1 772, 1 260, and 837 patients before treatment, and at
1, 3, 6, 12, 18, and 24 months after treatment, respectively. At 1 month, bowel
scores were the lowest for patients that had had radiation therapy, and urinary
irritative symptoms were the lowest for those who had had brachytherapy. There
were sexual function declines for all the treatment methods, with surgery having
the steepest decline; open radical prostatectomy (ORP) had a greater decline than
robot-assisted laparoscopic prostatectomy (RALP). Patients who underwent RALP had
a better return of sexual function, approaching that of brachytherapy and
radiation therapy at 24 months. Urinary incontinence (UI) also declined the most
in surgical patients, with RALP patients improving slightly more than ORP
patients at 12-24 months. CONCLUSIONS: Patients' HRQoL after prostate cancer
treatment varies by treatment method. Notably, sexual function recovers most for
RALP patients. UI remains worse at 24 months after surgery, compared to other
methods of prostate cancer treatment.
PMID- 28425195
TI - Revolutionary reform in psychiatric care in Italy: The abolition of forensic
mental hospitals.
PMID- 28425194
TI - Unlocking the limitations: Living with chronic obstructive pulmonary disease and
receiving care through telemedicine-A phenomenological study.
AB - AIMS AND OBJECTIVES: To describe the lived experiences of quality of life among a
group of patients living with chronic obstructive pulmonary disease who were
included in a telemedical intervention after hospitalisation for disease
exacerbation. BACKGROUND: Patients with chronic obstructive pulmonary disease
have high symptom burden, poor control of symptoms and a need for greater
requirements in care. Telemedicine can provide benefits for patients with chronic
obstructive pulmonary disease by improving self-management. DESIGN: Descriptive
phenomenological approach. METHODS: Ten in-depth interviews were conducted with
chronic obstructive pulmonary disease patients participating in a telemedical
intervention. The collected data were analysed using a descriptive
phenomenological research method. RESULTS: Living with chronic obstructive
pulmonary disease was experienced as creating physical and mental limitations of
the diseased body and an increasing identity as a patient, which led to impaired
quality of life. Being included in the telemedicine intervention increased
accessibility to healthcare services and support from telemedicine nurses. Self
measurement of health data increased participants' clinical insight and created a
mutual clinical language in dialogue with telemedicine nurses, which led to
increased quality of life. However, receiving care through telemedicine was also
experienced as a dual chore. CONCLUSIONS: Telemedicine can reduce the perceived
limitations imposed by chronic obstructive pulmonary disease through four key
elements: (i) improving accessibility to healthcare services, (ii) increasing
support from health professionals, (iii) strengthening clinical insight and (iv)
developing a mutual clinical language, thus increasing quality of life. The
transparency facilitated through telemedicine in this healthcare context
encourages open decision-making, where the participants can increase their
knowledge and improve acknowledgement of and collaboration with telemedicine
nurses. RELEVANCE TO CLINICAL PRACTICE: Telemedicine can be beneficial when
rethinking care for chronic obstructive pulmonary disease by providing knowledge
on how living with chronic obstructive pulmonary disease can affect the
experience of receiving care through telemedicine and further determine for whom
telemedicine is useful.
PMID- 28425196
TI - Bad blood contaminating germline databases?
PMID- 28425197
TI - Once doesn't count: Phenotype-driven gene hunting in cohorts.
PMID- 28425198
TI - The cell adhesion molecule EphA4 is involved in circadian clock functions.
AB - Circadian (~24 h) rhythms of cellular network plasticity in the central circadian
clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal
network in the SCN regulates photic resetting of the circadian clock as well as
stability of the circadian system during both entrained and constant conditions.
EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling
connections of neurons and astrocytes, is expressed in the SCN. To address
whether EphA4 plays a role in circadian photoreception and influences the
neuronal network of the SCN, we have analyzed circadian wheel-running behavior of
EphA4 knockout (EphA4-/- ) mice under different light conditions and upon photic
resetting, as well as their light-induced protein response in the SCN. EphA4-/-
mice exhibited reduced wheel-running activity, longer endogenous periods under
constant darkness and shorter periods under constant light conditions, suggesting
an effect of EphA4 on SCN function. Moreover, EphA4-/- mice exhibited suppressed
phase delays of their wheel-running activity following a light pulse during the
beginning of the subjective night (CT15). Accordingly, light-induced c-FOS (FBJ
murine osteosarcoma viral oncogene homolog) expression was diminished. Our
results suggest a circadian role for EphA4 in the SCN neuronal network, affecting
the circadian system and contributing to the circadian response to light.
PMID- 28425199
TI - Asymmetric Total Synthesis of Hispidanin A.
AB - Asymmetric total synthesis of the dimeric diterpenoid hispidanin A was
accomplished by non-catalytic Diels-Alder cycloaddition at room temperature. The
synthesis relies on iron-catalyzed coupling to construct a Z-configured
trisubstituted alkene, an iron-catalyzed radical cascade to generate a labdane
type diene, and both Yamamoto cationic polyene cyclization and palladium
catalyzed Stille coupling to generate a totarane-type dienophile.
PMID- 28425200
TI - High-dose calcineurin inhibitor-free everolimus as a maintenance regimen for
heart transplantation may be a risk factor for Pneumocystis pneumonia.
AB - BACKGROUND: Everolimus reduces the incidence of cardiac-allograft vasculopathy
(CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We
evaluated the safety of CNI-free everolimus for post-heart transplant (HTx)
patients. METHODS: We retrospectively reviewed the records of 36 consecutive
patients who had undergone an HTx between January 2006 and December 2013 in
National Cheng Kung University Hospital. All patients initially had been treated
with the standard tacrolimus regimen. The Study group-12 patients with CAV, renal
impairment, or a history of malignancy-were switched from tacrolimus to
everolimus. The Control group consisted of 19 patients who remained on the
standard regimen. The target everolimus trough concentration was 8-14 ng/mL. The
primary outcome was survival, and the secondary outcomes were bacterial, viral,
fungal, and other infections; Pneumocystis jirovecii pneumonia (PJP); and
rejection (>=2R). RESULTS: During a 53.3+/-25.6-month follow-up, the survival
rate, rejection rate, and number of infections, except for PJP, were not
significantly different between the two groups. In the Study group, 6 patients
were diagnosed with PJP 33+/-18.2 months after switching. None of the Control
group patients were diagnosed with PJP during follow-up. CONCLUSIONS: A high-dose
CNI-free everolimus maintenance regimen might yield a higher incidence of post
transplantation PJP.
PMID- 28425201
TI - Numerical analysis of crimping and inflation process of balloon-expandable
coronary stent using implicit solution.
AB - The paper presents an applied methodology for numerical finite element analysis
of coronary stent crimping and the free inflation process with the use of a
folded noncompliant angioplasty balloon. The use of an implicit scheme is
considered as the most original part of the work, as an explicit finite element
procedure is very often preferred. Hitherto, when the implicit solution was used
for the finite element solution, the simulated issue was largely simplified.
Therefore, the authors focused on the modelling methodology with minimum possible
simplification, ie, a full load path (compression and inflation in single
analysis), solid element discretization, and sophisticated contact models (bodies
with highly different stiffness). The obtained results are partially compared
with experimental data (radial force during the crimping procedure) and present
satisfactory compliance. The authors believe that presented methodology allow for
significant improvement of the obtained results, as well as potential extension
of the research scope, compared to previous efforts performed using the explicit
integration scheme. Moreover, the presented methodology is believed to be
suitable for sensitivity and optimization studies.
PMID- 28425202
TI - Examining solutions to missing data in longitudinal nursing research.
AB - PURPOSE: Longitudinal studies are highly valuable in pediatrics because they
provide useful data about developmental patterns of child health and behavior
over time. When data are missing, the value of the research is impacted. The
study's purpose was to (1) introduce a three-step approach to assess and address
missing data and (2) illustrate this approach using categorical and continuous
level variables from a longitudinal study of premature infants. METHODS: A three
step approach with simulations was followed to assess the amount and pattern of
missing data and to determine the most appropriate imputation method for the
missing data. Patterns of missingness were Missing Completely at Random, Missing
at Random, and Not Missing at Random. Missing continuous-level data were imputed
using mean replacement, stochastic regression, multiple imputation, and fully
conditional specification (FCS). Missing categorical-level data were imputed
using last value carried forward, hot-decking, stochastic regression, and FCS.
Simulations were used to evaluate these imputation methods under different
patterns of missingness at different levels of missing data. RESULTS: The rate of
missingness was 16-23% for continuous variables and 1-28% for categorical
variables. FCS imputation provided the least difference in mean and standard
deviation estimates for continuous measures. FCS imputation was acceptable for
categorical measures. Results obtained through simulation reinforced and
confirmed these findings. PRACTICE IMPLICATIONS: Significant investments are made
in the collection of longitudinal data. The prudent handling of missing data can
protect these investments and potentially improve the scientific information
contained in pediatric longitudinal studies.
PMID- 28425203
TI - Educational and career goal attainments in young adult childhood cancer
survivors.
AB - PURPOSE: Examine the educational and career outcomes of young adult childhood
cancer survivors. DESIGN AND METHODS: Descriptive study design using a survey
sent to 336 survivors. Quantitative and qualitative data were analyzed
separately. RESULTS: Only 50 completed surveys were returned. Having a central
nervous system tumor and radiation were associated with physical impairments.
Four themes also emerged: future as medical professionals, dreams fallen short,
peer relationships, and positive outlook on life. PRACTICE IMPLICATIONS:
Pediatric nurses caring for survivors should partner with oncology professionals
to support survivors to enrich their educational and career opportunities.
PMID- 28425204
TI - Ten tips to improve the likelihood of manuscript acceptance for publication in
JSPN.
PMID- 28425205
TI - Engineering the xylose-catabolizing Dahms pathway for production of poly(d
lactate-co-glycolate) and poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) in
Escherichia coli.
AB - Poly(lactate-co-glycolate), PLGA, is a representative synthetic biopolymer widely
used in medical applications. Recently, we reported one-step direct fermentative
production of PLGA and its copolymers by metabolically engineered Escherichia
coli from xylose and glucose. In this study, we report development of
metabolically engineered E. coli strains for the production of PLGA and poly(d
lactate-co-glycolate-co-d-2-hydroxybutyrate) having various monomer compositions
from xylose as a sole carbon source. To achieve this, the metabolic flux towards
Dahms pathway was modulated using five different synthetic promoters for the
expression of Caulobacter crescentus XylBC. Further metabolic engineering to
concentrate the metabolic flux towards d-lactate and glycolate resulted in
production of PLGA and poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) with
various monomer fractions from xylose. The engineered E. coli strains produced
polymers containing 8.8-60.9 mol% of glycolate up to 6.93 g l-1 by fed-batch
cultivation in a chemically defined medium containing xylose. Finally, the
biocompatibility of poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) was
confirmed by live/dead assay using human mesenchymal stem cells.
PMID- 28425206
TI - Considering Tangible Benefit for Interdependent Donors: Extending a Risk-Benefit
Framework in Donor Selection.
AB - From its infancy, live donor transplantation has operated within a framework of
acceptable risk to donors. Such a framework presumes that risks of living
donation are experienced by the donor while all benefits are realized by the
recipient, creating an inequitable distribution that demands minimization of
donor risk. We suggest that this risk-tolerance framework ignores tangible
benefits to the donor. A previously proposed framework more fully considers
potential benefits to the donor and argues that risks and benefits must be
balanced. We expand on this approach, and posit that donors sharing a household
with and/or caring for a potential transplant patient may realize tangible
benefits that are absent in a more distantly related donation (e.g. cousin,
nondirected). We term these donors, whose well-being is closely tied to their
recipient, "interdependent donors." A flexible risk-benefit model that combines
risk assessment with benefits to interdependent donors will contribute to donor
evaluation and selection that more accurately reflects what is at stake for
donors. In so doing, a risk-benefit framework may allow some donors to accept
greater risk in donation decisions.
PMID- 28425207
TI - BCG vaccination-induced suppurative lymphadenitis: four signs to pay attention
to.
AB - Suppurative lymphadenitis is one of the severe complication after BCG
vaccination, but its diagnostic criteria and treatment guidelines have not yet
been established. In this article, we describe a case of suppurative
lymphadenitis caused by BCG vaccination and propose diagnostic criteria and
treatment guidelines of the disease. The lymphadenitis was presented as skin
involving mass and was completely extirpated. Pathological evaluation revealed a
necrotising lymphadenitis, consistent with the diagnosis of BCG lymphadenitis.
The patient was administered adjuvant medical treatment with anti-TB medications
(Isoniazid and Rifampicin) for 3 months. At 6 months follow-up, the disease was
in complete remission without complications. We recommend focus on the following
four signs when diagnosing BCG lymphadenitis: (i) previous history of vaccination
on the ipsilateral side of the lesion, (ii) absence of any other infection signs,
(iii) absence of fever and (iv) isolated axillary or supraclavicular/cervical
lymph node enlargement proven by ultrasonography or computed tomography scan. BCG
vaccination-induced suppurative lymphadenitis can easily be overlooked, but
prompt, accurate diagnosis followed by appropriate surgical resection should
result in complete healing as in this case.
PMID- 28425208
TI - Nitrogenase Cofactor: Inspiration for Model Chemistry.
AB - The cofactor of nitrogenase is the largest and most intricate metal cluster known
in nature. Its reactivity, mode of action and even the precise binding site of
substrate remain a matter of debate. For decades, synthetic chemists have taken
inspiration from the exceptional structural, electronic and catalytic features of
the cofactor and have tried to either mimic the unique topology of the entire
site, or to extract its functional principles and build them into novel catalysts
that achieve the same-or very similar-astounding transformations. We review some
of the available model chemistry as it represents the various approaches that
have been taken from studying the cofactor, to eventually summarize the current
state of knowledge on catalysis by nitrogenase and highlight the mutually
beneficial role of model chemistry and enzymology in bioinorganic chemistry.
PMID- 28425209
TI - Identification of dynamic load for prosthetic structures.
AB - Dynamic load exists in numerous biomechanical systems, and its identification
signifies a critical issue for characterizing dynamic behaviors and studying
biomechanical consequence of the systems. This study aims to identify dynamic
load in the dental prosthetic structures, namely, 3-unit implant-supported fixed
partial denture (I-FPD) and teeth-supported fixed partial denture. The 3
dimensional finite element models were constructed through specific patient's
computerized tomography images. A forward algorithm and regularization technique
were developed for identifying dynamic load. To verify the effectiveness of the
identification method proposed, the I-FPD and teeth-supported fixed partial
denture structures were investigated to determine the dynamic loads. For
validating the results of inverse identification, an experimental force-measuring
system was developed by using a 3-dimensional piezoelectric transducer to measure
the dynamic load in the I-FPD structure in vivo. The computationally identified
loads were presented with different noise levels to determine their influence on
the identification accuracy. The errors between the measured load and identified
counterpart were calculated for evaluating the practical applicability of the
proposed procedure in biomechanical engineering. This study is expected to serve
as a demonstrative role in identifying dynamic loading in biomedical systems,
where a direct in vivo measurement may be rather demanding in some areas of
interest clinically.
PMID- 28425210
TI - CORRIGENDUM: Commentary on Pharmacometrics for Immunotherapy.
PMID- 28425211
TI - Importance of cytological subclassification of thyroid nodules with Bethesda
category III cytology (AUS/FLUS) into architectural atypia only and nuclear
atypia: A prospective study.
AB - BACKGROUND: The objective of this study was to compare two cytological
subcategories of thyroid nodules with Bethesda category III initial cytology.
METHODS: This was a prospective study. All patients with thyroid nodules > 1 cm
were eligible and 98 patients with category III cytology were selected. Cytology
was subcategorized into architectural atypia only (AA, n = 45) and nuclear atypia
(NA, n = 53). All patients underwent a second fine-needle aspiration (FNA). Only
patients whose second cytology was benign and ultrasonography was non-suspicious
were not referred for surgery. In these patients, the nodules were considered
benign. RESULTS: The second FNA more frequently revealed "benign cytology" in the
AA subcategory (44.4% vs. 24.5% in the NA subcategory). The second cytology
suggested "follicular neoplasm" or was "suspicious for follicular neoplasm"
(category IV) in 5 patients (11.1%) of subcategory AA and was "suspicious for
malignancy" (category V) in 13 (24.5%) of subcategory NA. Finally, malignancy was
diagnosed in 15.5% of cases of subcategory AA and in 41.5% of subcategory NA.
Follicular carcinoma was more frequent in subcategory AA, while classical
papillary carcinoma was more frequent in subcategory NA. Excluding cases of the
noninvasive encapsulated follicular variant of papillary carcinoma, malignancy
was diagnosed in 11.1% of patients of subcategory AA and in 35.8% of subcategory
NA. CONCLUSIONS: The results showed that subclassification of the Bethesda
category III improves cancer risk prediction, with potential repercussions for
clinical practice. Diagn. Cytopathol. 2017;45:604-607. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28425212
TI - Enantioselective Cascade Reaction for Synthesis of Quinolinones through
Synergistic Catalysis Using Cu-Pybox and Chiral Benzotetramisole as Catalysts.
AB - In contrast to the well-studied asymmetric catalyzed synthesis of
tetrahydroquinolines, the asymmetric methodologies toward 3,4-dihydroquinolin-2
ones are quite rare. Herein, the first asymmetric cascade reaction is reported
between ethynyl benzoxazinanones and mixed-anhydrides generated from aryl acetic
acids and pivaloyl chloride, based on synergistic catalysis. This allowed the
formation of attractive 3,4-dihydroquinolin-2-ones bearing two vicinal chiral
centers at C3 and C4 in high yields with excellent diastereo- and
enantioselectivities. A plausible chiral induction model for this reaction was
proposed. The utility of this methodology was exemplified by further elaboration
of the cyclization products by removal of the N-protecting groups.
PMID- 28425213
TI - Genotype-phenotype correlations in Cornelia de Lange syndrome: Behavioral
characteristics and changes with age.
AB - Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated
with unusual facial features, limb abnormalities, a wide range of health
conditions, and intellectual disability. Mutations in five genes that encode
(SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been
identified in up to 70% of individuals. Genetic cause remains unknown for a
proportion of individuals. There is substantial heterogeneity in all aspects of
CdLS but very little is known about what predicts phenotypic heterogeneity. In
this study, we evaluated genotype-phenotype associations in 34 individuals with
CdLS. Participants with NIPBL mutations had significantly lower self help skills
and were less likely to have verbal skills relative to those who were negative
for the NIPBL mutation. No significant differences were identified between the
groups in relation to repetitive behavior, mood, interest and pleasure,
challenging behavior, activity, impulsivity, and characteristics of autism
spectrum disorder whilst controlling differences in self help skills. Significant
correlations indicating lower mood, interest and pleasure, and increased
insistence on sameness with older age were identified for those who were NIPBL
mutation positive. The findings suggest similarities in the behavioral phenotype
between those with and without the NIPBL mutation once differences in self help
skills are controlled for. However, there may be subtle differences in the
developmental trajectory of these behaviors according to genetic mutation status
in CdLS.
PMID- 28425214
TI - Hypoglycemic and Antihyperglycemic Activities of Nine Medicinal Herbs Used as
Antidiabetic in the Region of Lubumbashi (DR Congo).
AB - The aim of this study was to assess the hypoglycemic and antihyperglycemic
activities of nine plants used as antidiabetic treatments in Lubumbashi and its
surroundings. Those are Albizia adianthifolia, Azanza garckeana, Cassia
occidentalis, Cassia sieberiana, Erythrina abyssinica, Gladiolus klattianus,
Rauvolfia caffra, Strychnos spinosa, and Vitex madiensis. Aqueous extracts,
obtained by decoction and maceration, were administered (500 mg/kg) per os to
guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral
glucose tolerance test (OGTT) conditions (glucose, 2 g/kg; follow-up over 210
min). For OGTT experiments, area under the curve of blood glucose levels, maximum
glucose concentration (Cmax), and time to reach Cmax (Tmax) were used to compare
test groups with the control conditions (glucose group). In hypoglycemic tests,
only three species induced significant (p < 0.001) lowering of normal glycemia:
A. adianthifolia (33% reduction), C. occidentalis (32%), and V. madiensis (43%);
in the same conditions, the positive control glibenclamide (6 mg/kg) induced a
blood glucose lowering of 55%. In OGTT conditions, all tested herbs were active,
with the highest inhibition of glycemia increases for V. madiensis (62%) and A.
adianthifolia (57%), compared with the hyperglycemic inhibition rate of
glibenclamide (50%). Oral glucose tolerance test conditions appear as essential
to detect the extracts most interesting for clinical use. These data support the
use of studied plants for diabetes treatment in traditional Congolese medicine
and indicate a good knowledge of tradipraticians in the field. Copyright (c) 2017
John Wiley & Sons, Ltd.
PMID- 28425215
TI - Lipid raft dynamics linked to sperm competency for fertilization in mice.
AB - It is well known that mammalian sperm acquires fertilization ability after
several maturation processes, particularly within the female reproductive tract.
In a previous study, we found that both glycosylphosphatidylinositol (GPI)
anchored protein (GPI-AP) release and lipid raft movement occur during the sperm
maturation process. In several genetic studies, release of GPI-AP is a crucial
step for sperm fertilization ability in the mouse. Here, we show that lipid raft
movement is also fundamental for sperm to be competent for fertilization by
comparing the sperm maturation process of two mouse inbred strains, C57BL/6 and
BALB/c. We found that ganglioside GM1 movement was exclusively reduced in BALB/c
compared with C57BL/6 among other examined sperm maturation parameters, such as
GPI-AP release, sperm migration to the oviduct, cholesterol efflux, protein
tyrosine phosphorylation and acrosome reaction, and was strongly linked to sperm
fertility phenotype. The relationship between GM1 movement and in vitro
fertilization ability was confirmed in other mouse strains, suggesting that lipid
raft movement is one of the important steps for completing the sperm maturation
process.
PMID- 28425216
TI - Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi-cohort
study.
AB - AIM: Studies have linked the use of inhaled corticosteroids (ICSs) to excess
pneumonia risk in chronic obstructive pulmonary disease patients. The risk in
asthma patients remains unclear. The objective of the present study was to
examine the risk of pneumonia with ICSs in asthma patients aged 12-35 years.
METHODS: We formed a cohort of asthma patients treated from 1990 to 2007 using
Quebec health insurance databases. Subjects were considered currently exposed if
they had had an ICS dispensed within the 60 days prior to their pneumonia index
event or matched person-moment. Secondary analyses investigated the risk of
pneumonia according to ICS dose and type. Rate ratios (RRs) and rate differences
(RDs) were both estimated through a quasi-cohort approach. RESULTS: The cohort
included 152 412 subjects, of whom 1928 had a pneumonia event during follow-up.
There was an increased risk of pneumonia associated with current use of ICSs [RR
1.83; 95% confidence interval (CI) 1.57, 2.14] or an excess risk of 1.44 cases
per 1000 person-years (RD 1.44; 95% CI 1.03, 1.85). There was an excess pneumonia
risk with low doses (RR 1.60; 95% CI 1.06, 2.45), moderate doses (RR 1.53; 95% CI
1.12, 2.08) and high doses (RR 1.96; 95% CI 1.64, 2.34) of ICSs, and with
budesonide (RR 2.67; 95% CI 2.05, 3.49) and fluticasone (RR 1.93; 95% CI 1.58,
2.36), specifically relative to no use. When accounting for potential protopathic
bias, the risk with current use of ICSs was attenuated (RR 1.48; 95% CI 1.22,
1.78). CONCLUSION: ICS use in asthma patients appears to be associated with an
increased risk of pneumonia and is present for both budesonide and fluticasone.
PMID- 28425217
TI - The release of pro-inflammatory cytokines is mediated via mitogen-activated
protein kinases rather than by the inflammasome signalling pathway in
keratinocytes.
AB - Toll-like receptors (TLRs) are expressed in the skin and airway epithelial
tissues, which are the most important sites of host-pathogen interactions. TLRs
recognize the 3-D structures of pathogen-associated molecules and are therefore
useful markers of the innate immune response. Here, we investigated the role of
lipopolysaccharides and monosodium urate (MSU) crystals in the activation of the
TLR and NOD-like receptor (NLR) pathways in human keratinocytes. Analysis of the
inflammasome compounds revealed that NOD-like receptor P3 and TLR4, both of which
are components of inflammasome complexes involved in the activation of
interleukin (IL)-1beta, were not expressed in keratinocytes. Transcriptomic
analysis showed that the combination of MSU and lipopolysaccharide priming did
not elicit significant results compared to MSU treatment, which induced the
expression of TLR2, IL-6 and IL-8/chemokine (C-X-C motif) ligand 8 CXCL8 in the
keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of
extracellular signal-regulated kinase 1/2 and MAPK14/p38alpha mitogen-activated
protein kinases. We concluded that MSU stimulates a pro-inflammatory response in
keratinocytes via mitogen-activated protein kinase pathway to induce production
of IL-8/CXCL8 chemokine (C-X-C motif) ligand 8 and TLR2.
PMID- 28425218
TI - Recurrence of congenital heart defects among siblings-a nationwide study.
AB - Congenital heart defects (CHD) constitute the largest group of congenital
malformations. In most families, only one person has CHD; however, the risk of
CHD increases for children born into families already affected. In this study,
all births from 1994 through 2009 were identified in the Medical Birth Registry
of Norway, including supplemental information on CHD from clinical and
administrative registers, as part of the CVDNOR project. By using the unique
personal identification number of each parent we were able to link 16,078 pairs
of twins, 445,584 pairs of full siblings, and 106,840 pairs of half-siblings.
Sibling recurrence risk ratio (RRR) was calculated using CHD status in the oldest
sibling as exposure and CHD status in the younger sibling as outcome, adjusted
for year of birth, maternal age, and maternal diabetes. Among full sibling pairs
with CHD in the older sibling, the younger sibling had CHD in 4.1% compared to
1.1% of the pairs without CHD in the older sibling (adjusted RRR 3.6; 95%
confidence interval (CI) 3.1-4.1). In same-sex twins the RRR was 14.0 (95% CI
10.6-18.6), and in opposite-sex twins the RRR was 11.9 (95% CI 7.1-19.9). For
half-siblings the RRR was 1.5 (95% CI 0.8-2.8). When restricting to severe types
of CHD, the RRR was 6.9 (95% CI 4.9-9.8) for full siblings. In 50% of the pairs
with recurrent CHD, the siblings had similar types of CHD. The high relative risk
of recurrence indicates that familial risk factors are important in the etiology
of CHD.
PMID- 28425219
TI - Resistance-modifying Activity in Vinblastine-resistant Human Breast Cancer Cells
by Oligosaccharides Obtained from Mucilage of Chia Seeds (Salvia hispanica).
AB - The multidrug resistance (MDR) phenotype is considered as a major cause of the
failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the
overexpression of drug efflux pumps of a P-glycoprotein. The development of
compounds that mitigate the MDR phenotype by modulating the activity of these
transport proteins is an important yet elusive target. Here, we screened the
saponification and enzymatic degradation products from Salvia hispanica seed's
mucilage to discover modulating compounds of the acquired resistance to
chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was
used to purify the hydrolysis degradation products. All compounds were tested in
eight different cancer cell lines and Vero cells. All compounds were noncytotoxic
at the concentration tested against the drug-sensitive and multidrug-resistant
cells (IC50 > 29.2 MUM). For the all products, a moderate vinblastine-enhancing
activity from 4.55-fold to 6.82-fold was observed. That could be significant from
a therapeutic perspective. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425220
TI - Associations between the Transsexual Voice Questionnaire (TVQMtF ) and self
report of voice femininity and acoustic voice measures.
AB - BACKGROUND: The Transsexual Voice Questionnaire (TVQMtF ) was designed to capture
the voice-related perceptions of individuals whose gender identity as female is
the opposite of their birth-assigned gender (MtF women). Evaluation of the
psychometric properties of the TVQMtF is ongoing. AIMS: To investigate
associations between TVQMtF scores and (1) self-perceptions of voice femininity
and (2) acoustic parameters of voice pitch and voice quality in order to evaluate
further the validity of the TVQMtF . A strong correlation between TVQMtF scores
and self-ratings of voice femininity was predicted, but no association between
TVQMtF scores and acoustic measures of voice pitch and quality was proposed.
METHODS & PROCEDURES: Participants were 148 MtF women (mean age 48.14 years)
recruited from the La Trobe Communication Clinic and the clinics of three doctors
specializing in transgender health. All participants completed the TVQMtF and 34
of these participants also provided a voice sample for acoustic analysis. Pearson
product-moment correlation analysis was conducted to examine the associations
between TVQMtF scores and (1) self-perceptions of voice femininity and (2)
acoustic measures of F0, jitter (%), shimmer (dB) and harmonic-to-noise ratio
(HNR). OUTCOMES & RESULTS: Strong negative correlations between the participants'
perceptions of their voice femininity and the TVQMtF scores demonstrated that for
this group of MtF women a low self-rating of voice femininity was associated with
more frequent negative voice-related experiences. This association was strongest
with the vocal-functioning component of the TVQMtF . These strong correlations
and high levels of shared variance between the TVQMtF and a measure of a related
construct provides evidence for the convergent validity of the TVQMtF . The
absence of significant correlations between the TVQMtF and the acoustic data is
consistent with the equivocal findings of earlier research. This finding
indicates that these two measures assess different aspects of the voice-related
experience. CONCLUSIONS & IMPLICATIONS: Evidence supporting the validity of the
TVQMtF is strong and indicates that it is a sound measure for capturing the MtF
woman's self-perceptions of her vocal functioning and how her voice impacts on
her everyday life.
PMID- 28425221
TI - Conceptualizing movement by expert Bobath instructors in neurological
rehabilitation.
AB - RATIONALE, AIMS, AND OBJECTIVES: Movement, a core aspect of physiotherapy
practice, and integral to the clinical reasoning process has undergone limited
theoretical development. Instead, research has focused on intervention
effectiveness embedded within the positivist paradigm. The purpose of this study
was to explore how expert neurorehabilitation therapists conceptualize movement
as part of their clinical reasoning. METHOD: A qualitative interpretive
descriptive approach consisting of stimulated recall using video-recorded
treatment sessions and in-depth interviews was used. Theoretical sampling was
used to recruit members of the International Bobath Instructors Training
Association (IBITA) who are recognized experts in neurorehabilitation. Interview
transcripts were transcribed verbatim. Data analysis was progressive, iterative,
and inductive. RESULTS: Twenty-two IBITA instructors from 7 different countries
volunteered to participate. They ranged in clinical experience from 12 to 40
years and instructor experience from 1 to 35 years. The conceptualization of
movement by the IBITA instructors involves the following elements: (1) movement
comprises the whole person and the whole body, not just individual body segments;
(2) active alignment of body segments is integral to movement performance; and
(3) efficient movement requires the relative integration of postural
control/stability and selective movement/mobility. CONCLUSIONS: The IBITA
instructors conceptualize movement from a person-centred perspective. The
integration of postural control and selective movement, with alignment and
variability as key components, forms the foundation of their understanding of
movement. Further investigation into the role of postural control in movement
recovery post central nervous system lesion is required. Likewise, the dimensions
of movement critical to the conceptualization of movement are not well understood
from the perspective of the physiotherapist or persons with neurological
impairments.
PMID- 28425222
TI - Class III antiarrhythmic drugs amiodarone and dronedarone impair KIR 2.1 backward
trafficking.
AB - Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias.
The subcellular level at which drugs interfere in trafficking pathways is largely
unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac
inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and
dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a
lesser extent dronedarone, causes serious adverse effects to several organs and
tissue types, including the heart. Both drugs have been described to interfere in
the late-endosome/lysosome system. Here we defined the potential interference in
KIR 2.1 backward trafficking by amiodarone and dronedarone. Both drugs inhibited
IK1 in isolated rabbit ventricular cardiomyocytes at supraclinical doses only. In
HK-KWGF cells, both drugs dose- and time-dependently increased KIR 2.1 expression
(2.0 +/- 0.2-fold with amiodarone: 10 MUM, 24 hrs; 2.3 +/- 0.3-fold with
dronedarone: 5 MUM, 24 hrs) and late-endosomal/lysosomal KIR 2.1 accumulation.
Increased KIR 2.1 expression level was also observed in the presence of Nav 1.5
co-expression. Augmented KIR 2.1 protein levels and intracellular accumulation
were also observed in COS-7, END-2, MES-1 and EPI-7 cells. Both drugs had no
effect on Kv 11.1 ion channel protein expression levels. Finally, amiodarone
(73.3 +/- 10.3% P < 0.05 at -120 mV, 5 MUM) enhanced IKIR2.1 upon 24-hrs
treatment, whereas dronedarone tended to increase IKIR2.1 and it did not reach
significance (43.8 +/- 5.5%, P = 0.26 at -120 mV; 2 MUM). We conclude that
chronic amiodarone, and potentially also dronedarone, treatment can result in
enhanced IK1 by inhibiting KIR 2.1 degradation.
PMID- 28425223
TI - Three families with mild PMM2-CDG and normal cognitive development.
AB - Congenital disorders of glycosylation (CDG) are caused by defective glycosylation
of proteins and lipids. PMM2-CDG is the most common subtype among the CDG. The
severity of PMM2-CDG is variable. Patients often have a recognizable phenotype
with neurological and multisystem symptoms that might cause early death. We
report six patients from three families who are diagnosed with a clinically mild
PMM2-CDG and have normal cognitive development. All these patients had delayed
gross motor skills with mild-to-moderate neurological findings. Cerebellar
hypoplasia was detected in all siblings for whom brain MRI was performed. In 5/6
children the Wechsler Intelligence Scale for Children (WISC) showed normal
cognitive development with full scale IQ scores ranging from borderline to
average. Four patients were diagnosed with PMM2-CDG at the age of 8 years or
later as their neurological symptoms were quite mild and they had been able to
participate in regular school programs. We report patients with
p.Val231Met/p.Arg239Trp and p.Ile120Thr/p.Gly228Cys genotypes which may cause
milder variants of PMM2-CDG.
PMID- 28425224
TI - Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat
posterior eye diseases.
AB - Effective drug delivery to the retina still remains a challenge due to ocular
elimination mechanisms and complex barriers that selectively limit the entry of
drugs into the eye. To overcome these barriers, frequent intravitreal injections
are currently used to achieve high drug concentrations in vitreous and retina.
However, these repetitive injections may result in several side effects. Recent
advancements in the field of nanoparticle-based drug delivery could overcome some
of these unmet needs and various preclinical studies conducted to date have
demonstrated promising results of nanotherapies in the treatment of retinal
diseases. Compared to the majority of commercially available ocular implants, the
biodegradable nature of most nanoparticles (NPs) avoids the need for surgical
implantation and removal after the release of the payload. In addition, the
sustained drug release from NPs over an extended period of time reduces the need
for frequent intravitreal injections and the risk of associated side effects. The
nanometer size and highly modifiable surface properties make NPs excellent
candidates for targeted ocular drug delivery. Studies have shown that
nanocarriers enhance the intravitreal half-life and thus bioavailability of a
number of drugs including proteins and peptides. In addition, they have shown
promising results in delivering genetic material to the retinal tissues by
protecting it from possible intravitreal degradation. This review covers the
various challenges associated with drug delivery to the posterior segment of the
eye, particularly the retina, and highlights the application of nanocarriers to
overcome these challenges in context with recent advances in preclinical studies.
WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article
is categorized under: Therapeutic Approaches and Drug Discovery > Emerging
Technologies Implantable Materials and Surgical Technologies > Nanomaterials and
Implants.
PMID- 28425225
TI - Green Processing of Lignocellulosic Biomass and Its Derivatives in Deep Eutectic
Solvents.
AB - The scientific community has been seeking cost-competitive and green solvents
with good dissolving capacity for the valorization of lignocellulosic biomass. At
this point, deep eutectic solvents (DESs) are currently emerging as a new class
of promising solvents that are generally liquid eutectic mixtures formed by self
association (or hydrogen-bonding interaction) of two or three components. DESs
are attractive solvents for the fractionation (or pretreatment) of lignocellulose
and the valorization of lignin, owing to the high solubility of lignin in DESs.
DESs are also employed as effective media for the modification of cellulose to
afford functionalized cellulosic materials, such as cellulose nanocrystals. More
interestingly, biomassderived carbohydrates, such as fructose, can be used as one
of the constituents of DESs and then dehydrated to 5-hydroxymethylfurfural in
high yield. In this review, a comprehensive summary of recent contribution of
DESs to the processing of lignocellulosic biomass and its derivatives is
provided. Moreover, further discussion about the challenges of the application of
DESs in biomass processing is presented.
PMID- 28425226
TI - A review of pediatric pulmonary hypertension with new guidelines.
AB - This study aims to review pediatric pulmonary hypertension (PH) by comparing the
guidelines of the European Society of Cardiology (ESC)/European Respiratory
Society (ERS), the American Heart Association (AHA)/American Thoracic Society
(ATS), and the European Pediatric Pulmonary Vascular Disease Network (EPPVDN).
All three sets of guidelines define PH as having a mean pulmonary artery pressure
of >=25 mmHg and accept the validity of the World Health Organization (WHO)
classification system. Every child with a high index of suspicion for PH should
undergo an initial work-up of chest X-rays, electrocardiography, and
echocardiography. The AHA/ATS guidelines emphasize the necessity of cardiac
catheterization and hemodynamic studies. As mentioned in the AHA/ATS guidelines,
the symptoms and tests that can detect PH include right ventricle failure, WHO
functional class, syncope, echocardiography findings, hemodynamic data, brain
natriuretic peptide (BNP)/N-terminal pro-BNP, the 6-min walk test, and
cardiopulmonary exercise tests. The EPPVDN guidelines refer to positive acute
vasoreactivity test results and growth as risk factors. All three guidelines
highlight the importance of treating and following affected children in
specialized centers and recommend calcium channel blockers as a first-line
treatment in children (aged >12 months) who have a positive acute vasoreactivity
test. Children with PH have distinct clinical features. In order to overcome the
controversies related to the optimal management of pediatric PH, well-designed
clinical studies should be carried out on a large cohort of affected children.
PMID- 28425227
TI - Primary Sjogren's syndrome in patients with celiac disease.
AB - BACKGROUND/AIM: Many autoimmune diseases occur concomitantly with celiac disease
(CD). We aimed to determine the frequency of Sjogren's syndrome (SS) in CD
patients based on SS-specific serology verified by minor labial salivary biopsy.
MATERIALS AND METHODS: Eight-two patients with CD were included in the study.
After examination for objective evidence of sicca complex, all patients were
tested for serological presence of rheumatoid factor (RF) and antinuclear
antibodies (ANAs) and for ANA profile. Minor labial salivary biopsy was performed
for patients with positive serology and/or clinical signs of SS. RESULTS: Of the
patients included, 24 (29.3%) had dry eye symptoms while 20 (24.4%) had dry mouth
symptoms. Dry eye was detected by Schirmer test in 10 patients (12.2%) and by
ocular staining score in only 2 patients (2.4%). All samples were negative for RF
while 12 (14.6%) samples were positive for ANAs. Of 82 patients with CD, the
diagnosis of SS was established in only one patient (1.2%), while one patient
(1.2%) was diagnosed with morphea and 4 patients (4.9%) were classified as having
undifferentiated connective tissue disease. CONCLUSION: The prevalence of SS in
CD is low, so there is no need for serologic screening of all patients with CD
for SS.
PMID- 28425228
TI - The effects of the chloride:sodium ratio on acid-base statusand mortality in
septic patients.
AB - BACKGROUND/AIM: Calculation of the chloride:sodium (Cl-:Na+) ratio is proposed to
enable a quick evaluation of the effect of Cl- and Na+ on the acid-base balance
in critically ill patients. In the present study, the relationship of the Cl-:Na+
ratio of septic patients with acid-base status and ICU mortality were
investigated. MATERIALS AND METHODS: In our two-center study, 434 patients who
were diagnosed with sepsis were included. The patients were divided into three
groups: low (<0.75), normal (>=0.75, <0.80), and high (>=0.80) Cl-:Na+ ratio
groups. Patients' demographic data, blood gas values, length of ICU stay, and ICU
mortality were recorded. RESULTS: In the low and high groups, ICU mortality was
significantly higher than in the normal group (29.3%, 37.1%) (P = 0.005). There
was a negative correlation between the Cl:Na+ ratio and each of HCO3-, standard
base excess, and PaCO2 (r2 = 0.21, r2 = 0.19, and r2 = 0.17) (P < 0.001 for
each). In the multivariate analysis, the ICU mortality was increased 2.6-fold
(1.2-5.8) by low Cl-:Na+ ratio (P = 0.019). CONCLUSION: The Cl-:Na+ ratio is a
useful parameter for showing the relationship between Cl- and Na+ and their
impact on acid-base status. Low Cl-:Na+ ratio at ICU admission can be used as a
prognostic indicator for increased ICU mortality in septic patients.
PMID- 28425229
TI - Association of B7-H4 gene polymorphisms in urothelial bladder cancer.
AB - BACKGROUND/AIM: We aimed to study polymorphisms of the B7-H4 gene in order to
evaluate a possible association in urothelial carcinoma, as it is highly
expressed in cancer tissues. MATERIALS AND METHODS: In this study B7-H4 gene
rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in
paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a
control group including 30 patients without bladder cancer. RESULTS: We detected
that the rs10754339 polymorphism was more frequent in the cancer patients when
compared with the control group (P < 0.05). Only the rs3738414 polymorphism
showed a statistically significant difference in frequency between pathologic
diagnostic groups. CONCLUSION: The rs10754339 AA genotype distribution was found
to have a higher frequency whereas the rs3738414 AG genotype distribution was
lower in the bladder cancer group (P < 0.05). None of the genotype distributions
showed a significant difference from the control group for the rs10801935
polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic
marker in urothelial carcinoma.
PMID- 28425230
TI - Attitudes, wishes, and needs of diabetes patients and their relatives: Turkish
data from the DAWN2 study.
AB - BACKGROUND/AIM: The DAWN2 (Diabetes Attitudes, Wishes, and Needs) study was
conducted in order to ascertain the wishes, needs, and attitudes of diabetes
patients, their relatives, and healthcare professionals. The study was conducted
across 17 countries, including Turkey, and its objective was to introduce
policies that could successfully meet these requirements. In this article, the
needs, wishes, and attitudes of diabetes patients and their relatives in Turkey
are compared with those from other countries. MATERIALS AND METHODS: Eighty
patients with type 1 diabetes, 426 patients with type 2 diabetes, and 126
relatives of patients with diabetes were included in the study. RESULTS:
Depression was common in individuals suffering from diabetes and the quality of
life was negatively affected. The primary concerns of diabetic individuals were
general hypoglycemic attacks, nocturnal hypoglycemia, and gaining weight.
Analysis of self-care activities showed that physical activity, foot care, and
frequency of blood glucose measurement were below average in Turkey as compared
to other countries. CONCLUSION: DAWN2 is the first study of its kind. The
problems and shortcomings related to diabetes care and management in Turkey are
once again revealed with this study, and important data and opportunities to
improve them are presented.
PMID- 28425231
TI - The relationship between physical fitness and falling risk and fear of falling in
community-dwelling elderly people with different physical activity levels.
AB - BACKGROUND/AIM: The aim of this research was to determine the effects of physical
activity level (PAL) and physical fitness on falling parameters in community
dwelling elderly people. MATERIALS AND METHODS: Seventy-six elderly people were
grouped as low PAL group (group 1, n: 38) and high PAL (group 2, n: 38) according
to their PAL scores. PAL was measured by the Physical Activity Scale for the
Elderly and muscle strength, muscle endurance, aerobic endurance, and flexibility
tests were applied; body mass index (BMI) was calculated for physical fitness
measurement. Fall assessment included falling risk (Berg Balance Scale), dynamic
balance (Time Up and Go Test), and fear of falling (FOF) (Falls Efficacy Scale)
evaluation. RESULTS: While physical fitness parameters except flexibility in
group 2 were significantly better than they were in group 1 (P < 0.05), no
significant difference was found between the groups with regard to fall
assessments (P ? 0.05). In both groups, while physical fitness parameters except
BMI showed a positive and low or medium significant correlation with falling risk
and FOF, the same fitness parameters showed a negative and low or medium
significant correlation with dynamic balance. CONCLUSION: The results show that
PAL may have an indirect effect on fall parameters by increasing physical
fitness.
PMID- 28425232
TI - Effect of familial Mediterranean fever on sexual and reproductive health in
women.
AB - BACKGROUND/AIM: The aim of this study was to investigate the relationship between
familial Mediterranean fever and female sexual dysfunction and premenstrual
syndrome. MATERIALS AND METHODS: This study included 36 patients with familial
Mediterranean fever and 33 healthy volunteers. Familial Mediterranean fever was
diagnosed according to the Tel Hashomer criteria and familial Mediterranean fever
mutations were identified in all of the patients. The patients and healthy
volunteers were compared in terms of anxiety, depression, sexual dysfunction, and
premenstrual syndrome, and a model was created that describes the relationships
among these variables. RESULTS: We found statistically significant differences
between the groups in terms of anxiety, premenstrual syndrome, and Golombok Rust
Inventory of Sexual Satisfaction frequency and vaginismus subscale scores. There
was no difference in depression scores between the groups. CONCLUSION: Familial
Mediterranean fever is a rheumatic disease that predisposes patients to sexual
dysfunction and premenstrual syndrome, which emerges as direct and indirect
psychological factors.
PMID- 28425233
TI - Comparison of the standard GnRH antagonist protocol and the luteal phase
estradiol/GnRH antagonist priming protocol in poor ovarian responders.
AB - BACKGROUND/AIM: The aim of the study was to compare the luteal estradiol
patch/GnRH antagonists priming protocol (LPP) with the standard GnRH antagonist
protocol in poor ovarian responders (PORs) in terms of the outcomes of in vitro
fertilization (IVF) treatment. MATERIALS AND METHODS: IVF outcomes of 265 cycles
in 265 patients (106 in the LPP group, 159 in the standard GnRH antagonist group)
were evaluated retrospectively. RESULTS: Mean length of stimulation (11.4 +/- 2.7
vs. 10.0 +/- 2.7 days; P < 0.05) and the total gonadotropin dose (3403 +/- 1060
vs. 2984 +/- 1112) used were significantly greater in the LPP group than in the
standard GnRH antagonist protocol group. The mean number of oocytes retrieved
(3.5 +/- 2.6 vs. 3.7 +/- 2.8), the number of mature oocytes (2.8 +/- 2.2 vs. 2.6
+/- 2.2), fertilization rates (65% vs. 62%), the number of embryos transferred
(1.6 +/- 0.6 vs. 1.7 +/- 0.6), and implantation rates (16% vs. 13%) were similar.
The cancellation rate did not significantly differ between the groups (9.4% vs.
13.2%). There were no significant differences in the clinical pregnancy (11.3%
vs. 13.2%) or live birth rates per patient (3.8% vs. 9.4%) and clinical pregnancy
(18.8% vs. 22.6%) or live birth rates per embryo transfer (6.3% vs. 12.9%)
between the groups. CONCLUSION: LPP does not improve IVF outcomes when compared
with the standard GnRH antagonist protocol in PORs.
PMID- 28425234
TI - Alpha-1 Antitrypsin Levels and Polymorphisms in Interstitial Lung Diseases.
AB - BACKGROUND/AIM: Alpha-1 antitrypsin deficiency may be a potential predisposing
factor for interstitial lung fibrosis. We investigated alpha-1 antitrypsin levels
and its polymorphisms in patients with interstitial lung disease. MATERIALS AND
METHODS: A total of 103 interstitial lung disease patients were compared.
RESULTS: The mean alpha-1 antitrypsin level in idiopathic interstitial pneumonia
patients was 1.67 +/- 0.33 g/L, and it was 1.54 +/- 0.37 g/L in patients with
nonidiopathic interstitial pneumonia (P = 0.13). Low alpha-1 antitrypsin levels
were more frequently observed in nonidiopathic interstitial pneumonia patients
compared with idiopathic interstitial pneumonia, but the difference was not
statistically significant (8.9% vs. 0%, respectively, P = 0.4). In 100 patients,
the normal PiMM genotype was detected, while abnormal ones (PiMZ, n = 2, 1.9%;
PiMS, n = 1, 0.97%) were determined in three cases. When the frequency of alpha-1
antitrypsin polymorphism in interstitial lung disease patients was compared with
the data of the healthy population, no significant difference was detected for
the PiMZ and PiMS variants (P = 0.15 and P = 0.44, respectively). CONCLUSION:
Lower levels of serum alpha-1 antitrypsin were more frequent in nonidiopathic
interstitial pneumonia patients than idiopathic interstitial pneumonia without an
increase in genetic polymorphism. The difference was not statistically
significant.
PMID- 28425235
TI - A study on the validity and reliability of the Amblyopia andStrabismus
Questionnaire (A&SQ) in Turkish.
AB - BACKGROUND/AIM: This study aims to evaluate the reliability and validity of the
Amblyopia and Strabismus Questionnaire (AandSQ) that is translated into Turkish.
MATERIALS AND METHODS: This is a methodological study. A total of 149 patients
took part in the survey research between December 2012 and June 2014 in an
university hospital, and 37 were retested. Cronbach's alpha coefficient was used
for the questionnaire's reliability analysis. RESULTS: Cronbach's alpha
coefficients for the subscales of fear of losing the better eye, distance
estimation, visual disorientation, double vision, and social contact and
appearance were found to be 0.80, 0.88, 0.95, 0.80, and 0.81, respectively. Five
factors determined by the exploratory factor analysis explained 69.87% of the
total variance. CONCLUSION: The Turkish version of the AandSQ is found as a
reliable and valid scale for analyzing Turkish society. The AandSQ might be
helpful for measuring quality of life in patients with strabismus.
PMID- 28425236
TI - Predictors of health related quality of life in childhood epilepsy and comparison
with healthy children: findings from an Indian study.
AB - BACKGROUND/AIM: Children with epilepsy have reduced health-related quality of
life (HRQOL) due to disease and medications. We aimed to assess child-reported
HRQOL in Indian children with epilepsy and compare it with that in healthy
children. MATERIALS AND METHODS: A cross-sectional study of 256 children with
epilepsy aged between 5 and 18 years on antiepileptic drug (AED) treatment for at
least 3 months was performed and 125 age and sex matched healthy children were
included. A generic version of the Pediatric Quality of Life (PedsQL version 4)
scale was used to assess HRQOL. RESULTS: Children with epilepsy had diminished
scores in total score and all subdomains of PedsQL as compared to healthy
children. Children with epilepsy on polytherapy had diminished HRQOL compared
with those on monotherapy. Children with generalized seizures or with symptomatic
epilepsy had diminished HRQOL. Significant predictors of poor HRQOL were adverse
drug reactions (ADRs) to AED, polytherapy, longer duration of epilepsy, shorter
seizure-free interval, and seizure frequency. CONCLUSION: Children with epilepsy
have diminished HRQOL than healthy children in all subdomains of PedsQL.
Significant predictors are ADRs to AED, polytherapy, longer duration of epilepsy,
shorter seizure-free interval, and seizure frequency. Comprehensive management of
children with epilepsy must go beyond seizure control.
PMID- 28425237
TI - The efficacy of narrowband UVB treatment in pediatric vitiligo: a retrospective
analysis of 26 cases.
AB - BACKGROUND/AIM: Narrowband UVB (Nb UVB) treatment is commonly used for the
management of psoriasis and atopic dermatitis, and is less often used for
vitiligo in children. The aim of this study was to evaluate the efficacy and
short-term safety of Nb UVB phototherapy in children diagnosed with vitiligo
retrospectively. MATERIALS AND METHODS: A total of 26 patients younger than 18
years with the diagnosis of vitiligo and managed with Nb UVB phototherapy as
documented in archive records were evaluated. Clinical response was assessed
according to repigmentation of the lesions: good response when there was more
than 75% repigmentation, moderate response when there was 25%-74% repigmentation,
poor response when repigmentation was less than 24%, and unresponsive when there
was no pigmentation and new lesions occurred. RESULTS: A total of 26 patients
received Nb UVB treatment; 14 were girls and 12 were boys. The age at onset of
the disease varied between 2 and 18 years, with a mean age of onset of 10.07 +/-
4.53 years. Repigmentation rate of >75% was detected in 45.4% of cases.
CONCLUSION: Nb UVB phototherapy seems to be a well-tolerated effective and safe
treatment option in children, especially those unresponsive to topical treatment
and those with widespread lesions. However, long-term risks such as
photocarcinogenesis and photoaging should kept in mind.
PMID- 28425238
TI - Depression and Parkinson disease: prevalence, temporal relationship, and
determinants.
AB - BACKGROUND/AIM: Comorbidity of depression in Parkinson disease (PD) is a major
factor that changes patients' quality of life. However, the neurobiological and
sociodemographic risk factors for this comorbidity are not well studied. In this
study, we aimed to define the prevalence, temporal relationship, and psychosocial
and clinical determinants of depression comorbid with PD. MATERIALS AND METHODS:
Fifty-five PD patients were evaluated with SCID, a data form that assessed
sociodemographic and PD-related variables, UPDRS III, HAM-D, HAM-A, MMSE, and the
Apathy Evaluation Scale. RESULTS: Depression (lifetime: 45.5%, last month: 25.5%,
before PD: 20%) was the most frequent psychiatric diagnosis. The major
determinants of depression in the last month and depression before PD were early
onset of PD and young age. Patients on pramipexole treatment were less likely to
be diagnosed with depression in the last month. Other sociodemographic and PD
related variables were not significantly different for lifetime, last month, and
pre-PD depression diagnosis compared to their counterparts. CONCLUSION:
Depression is prevalent both before and after patient gets a PD diagnosis.
Depression is not only the result of PD-related life changes but it is also a
preceding factor that may decrease the age of PD onset.
PMID- 28425239
TI - An 8-week thoracic spine stabilization exercise program improves postural back
pain, spine alignment, postural sway, and core endurance in university students:a
randomized controlled study.
AB - BACKGROUND/AIM: To investigate the effects of an 8-week thoracic stabilization
exercise program on back pain, spinal alignment, postural sway, and core
endurance in university students. MATERIALS AND METHODS: University students were
randomly allocated into exercise (n: 28) and control (n: 25) groups. The exercise
program was carried out 3 days a week for 8 weeks. Postural pain, spinal
alignment, postural sway, and core endurance were assessed via visual analogue
scale, Spinal Mouse, Biodex Balance System, and McGill's trunk muscle endurance
tests at the baseline and after 8 weeks of training. RESULTS: Differences were
observed for postural pain, thoracic and lumbar curvature, dynamic stability
index (eyes closed), and core endurance scores in the exercise group between
baseline and week 8 (P < 0.05) and all the parameters were significantly
different when compared to those of the control group (P < 0.05). CONCLUSION: The
program decreased postural pain, spinal curvatures, and postural sway, and
increased core endurance in university students. The program can be effective in
postural pain and misalignment of spine problems related to core weakness and
balance disorders.
PMID- 28425240
TI - Oral lichen planus: a 4-year clinical follow-up study.
AB - BACKGROUND/AIM: This study aimed to examine oral lichen planus (OLP) cases
histopathologically and cytologically, describe different clinical aspects of OLP
manifestations, and associate different OLP clinical forms with self-reported
oral health and with local and systemic risk factors. MATERIALS AND METHODS: All
patients with a referral diagnosis of OLP received biopsies. The histological
evaluation assessed infiltration with lymphocytes, epithelial hyperplasia, and
hyperkeratosis. Histology was used to validate the OLP diagnosis and to evaluate
the malignant transformation of OLP lesions. Clinical manifestations of OLP and
potential local oral environment-related risks were clinically assessed. Systemic
risks were evaluated by a structured questionnaire. RESULTS: A total of 133
patients with a histologically confirmed OLP diagnosis were followed. There were
more females (N = 109) than males (N = 24) and the majority of patients were
older than 50 years. The reticular form (45.1%) was the most prevalent clinical
form followed by the erosive-ulcerative form (33.8%). The histological
characteristics were most pronounced in the erosive-ulcerative form. Of the OLP
cases, 2.3% had a malignant transformation. CONCLUSION: Reticular and erosive
ulcerative were the most prevalent OLP forms. There were more female than male
OLP patients. Except for medication use, there were no statistically significant
differences among different clinical OLP forms in either local or systemic risk
factor distributions.
PMID- 28425241
TI - Incidence of cancer in the Turkish Republic of Northern Cyprus.
AB - BACKGROUND/AIM: This study analyzed the incidence, trends, and common types of
cancer in the Turkish Republic of Northern Cyprus (TRNC). MATERIALS AND METHODS:
This study is based on data collected from the office of the North Cyprus Cancer
Registry, Ministry of Health, for 2007-2012. Data were arranged on the basis of
age group, sex, and cancer site. Age standardized incidence rates (ASRs) were
estimated with the world standard population. EVIEWS (version 9) software was
used for statistical analysis. RESULTS: Of 1395 registered cases, 52.33% (730)
were reported in men and 47.67% (665) in women. The crude incidence rate was
96.41 in men and 101.74 in women. The average annual ASR was 88.88 in men and
87.76 in women with the cumulative rate of 21.47% and 14.69% in men and women,
respectively. The most common cancers in men were skin (ASR 15.62), prostate (ASR
11.23), bladder (ASR 11.71), lung (ASR 8.01), and colorectal cancer (ASR 7.61),
while in women these were breast (ASR 24.07), thyroid (ASR 14.93), skin (ASR
10.75), colorectal (ASR 6.05), and lymphoma (ASR 4.79). Linear regression
analysis confirmed rising trends for both men's (10.79, P <= 0.03) and women's
(14.67, P <= 0.04) cancers. CONCLUSION: Our findings revealed an increasing trend
of cancer incidence in the TRNC. For control and prevention, public awareness of
the risk factors and proper screening programs should be recommended.
PMID- 28425242
TI - Evaluation of serum uric acid levels in psoriasis vulgaris.
AB - BACKGROUND/AIM: Psoriasis has been accepted as a systemic disease and it is known
to be associated with various disorders including metabolic syndrome. High serum
uric acid levels are also associated with the components of metabolic syndrome.
In this study, we aimed to determine serum uric acid levels in patients with
psoriasis and the association of uric acid levels with disease activity by taking
the presence of metabolic syndrome criteria into account, since it is one of the
most important factors that affect serum uric acid levels. MATERIALS AND METHODS:
In this cross-sectional study, we evaluated 70 psoriasis patients and 70 healthy
individuals who were matched with the patients according to the presence of
metabolic syndrome. We evaluated the demographic features, levels of serum uric
acid, Psoriasis Area Severity Index (PASI) scores, presence of psoriatic
arthritis, nail involvement, and metabolic syndrome criteria of the patients.
RESULTS: Serum uric acid levels of psoriasis patients were significantly higher
than those of controls. There was a positive correlation between PASI scores and
serum uric acid levels of the patients. CONCLUSION: As hyperuricemia had a close
relationship with psoriasis and PASI scores, we suggest monitoring patients with
psoriasis for serum uric acid levels during treatment and follow-up.
PMID- 28425243
TI - The assessment of work productivity and activity impairment in Behcet's disease.
AB - BACKGROUND/AIM: The aim of this study was to assess the relationships between the
course of Behcet's disease (BD), disease-specific fears, and work productivity
and activity impairment. MATERIALS AND METHODS: In this cross-sectional study,
110 consecutive BD patients were included. The Work Productivity and Activity
Impairment questionnaire was used. RESULTS: In the group of employed patients,
30.41% had missed work during the previous week. The mean percentages of daily
activity impairment were higher in patients with musculoskeletal involvement
(39.81 +/- 33.61%) compared to those without (23.48 +/- 32.45%) (P = 0.008). A
greater decrease in working hours was observed in patients with eye involvement
(45.52 +/- 15.29 h) compared to those without (54.15 +/- 15.29 h) (P = 0.007).
More of the male patients (67.8%) were afraid of losing their jobs compared to
females (30%) (P = 0.000). CONCLUSION: The highest levels of lost productivity
and the most severe effects on daily life are consequences of eye and
musculoskeletal involvement in the study population. More effective therapeutic
approaches are required to improve the working lives of patients with BD.
Moreover, male patients had a higher fear of losing their jobs, suggesting a
match between the expected clinical course and the predictions of BD patients.
PMID- 28425244
TI - Genetic association analysis of ERBB4 polymorphisms with the risk ofschizophrenia
susceptibility in a Jordanian population of Arab descent.
AB - BACKGROUND/AIM: The ERBB4 gene encodes a transmembrane tyrosine kinase and is
considered to be one of the risk genes of schizophrenia. Although there is
evidence of the roles of genes and the environment in the etiology of
schizophrenia, a comprehensive biological and genetic background of the disease
is still lacking. The aim of this study is to assess whether genetic variation in
the human ERBB4 gene is associated with vulnerability to schizophrenia in the
Jordanian Arab population. MATERIALS AND METHODS: A total of 185 inpatients with
schizophrenia participated in this study and 195 healthy genetically homogeneous
individuals were also used as controls. Two genetic variants, rs839523 (G/A,
intron 2) and rs3748962 (A/G, exon 27), encompassing the ERBB4 gene were
genotyped using DNA sequencing. RESULTS: The results revealed a strong and
statistically significant genetic association of rs839523 with schizophrenia (P =
0.002 for allele and P = 0.006 for genotype). CONCLUSION: This study provides
strong statistical evidence that there is an association between the ERBB4 gene
and schizophrenia in a Jordanian population of Arab descent.
PMID- 28425245
TI - Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome
in advanced nonsmall cell lung cancer patients.
AB - BACKGROUND/AIM: The association between polymorphisms of xenobiotic/drug
metabolizing enzymes and TP53 and response to chemotherapy and survival of
patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In
this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro)
polymorphisms and response to platinum-based chemotherapy and survival in 137
advanced stage NSCLC patients were investigated. MATERIALS AND METHODS: Genetic
polymorphism analyses were determined by polymerase chain reaction (PCR) coupled
with restriction fragment length polymorphism (RFLP). RESULTS: The patients with
TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those
with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed
these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser),
GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1
polymorphic genes that we have previously genotyped in the same patients (Ada et
al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that
adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53
(Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as
compared to wild-type genotypes (HR, 6.03; 95% CI, 1.39-26.04, P = 0.016).
CONCLUSION: These results show that combined variant genotypes of TP53 (Arg72Pro,
Pro72Pro) and CYP1A1 (Ile/Val, Val/Val) are associated with worsening of survival
in NSCLC patients.
PMID- 28425246
TI - Repeated prevalence studies of nosocomial infections in one university hospital
in Serbia.
AB - BACKGROUND/AIM: Nosocomial infections occur worldwide and affect both developed
and resource-poor countries. The aim of this paper was to determine the
prevalence and risk factors for nosocomial infections in one Serbian hospital.
MATERIALS AND METHODS: Three-point prevalence surveys were conducted in the
Clinical Center of Kragujevac (1240 beds). The standard definitions for
nosocomial infections of the Centers for Diseases Control and Prevention were
used. The authors conducted surveys according to the same protocol. RESULTS: The
prevalence of infected patients and the overall prevalence of nosocomial
infections was 6.2% and 7.1% in 2003, 4.6% and 4.6% in 2005, and 7.6% and 8.7% in
2009, respectively. In all three studies, the risk factors for nosocomial
infections were older age, intravascular catheters, urinary catheters, longer
hospital stays, hospitalization in an intensive care unit, and surgeries.
According to the multivariate regression analysis, a prolonged hospitalization
and use of a urinary catheter were independent risk factors for nosocomial
infections in the first and second study. CONCLUSION: The overall healthcare
associated infection prevalence in our hospital increased from 2003 to 2009, and
this was an incentive for a better definition of infection control priorities in
high-risk departments.
PMID- 28425247
TI - Meloxicam and diclofenac do not change VEGF and PDGF-ABserum levels of platelet
rich plasma.
AB - BACKGROUND/AIM: Platelet-rich plasma (PRP) application has gained widespread
interest for musculoskeletal injuries. Nonsteroidal antiinflammatory drugs are
frequently used in sports medicine before and/or after PRP application. Our study
seeks to determine whether serum levels of platelet-derived growth factor-AB
(PDGF-AB) and vascular endothelial growth factor (VEGF) levels of PRP would be
affected by nonsteroidal antiinflammatory drugs. MATERIALS AND METHODS: Two
different final concentrations of diclofenac (0.5 MUg mL-1 and 2.5 MUg mL-1),
meloxicam (0.8 MUg mL-1 and 2.0 MUg mL-1), and acetylsalicylic acid (final
concentration 450 MUm) were obtained in separate tubes with PRPs prepared from 20
healthy male volunteers. Medicine-free PRP was the control group. Growth factors
were measured using ELISA. RESULTS: PDGF-AB and VEGF serum levels did not change
with diclofenac, meloxicam, or acetylsalicylic acid addition. PDGF-AB and VEGF
serum levels correlated with each other. CONCLUSION: Diclofenac, meloxicam, and
acetylsalicylic acid did not affect PDGF-AB and VEGF serum levels.
PMID- 28425248
TI - The effect of transcatheter aortic valve implantation on mean platelet volume.
AB - BACKGROUND/AIM: Transcatheter aortic valve implantation (TAVI) is an innovative
approach to the treatment of aortic stenosis (AS) as an alternative to surgery in
high-risk patients. Mean platelet volume (MPV) is considered an indicator of
endothelial dysfunction, platelet function, and activation. In this study, we
aimed to investigate MPV changes in patients undergoing TAVI. MATERIALS AND
METHODS: This study included 100 patients diagnosed with symptomatic severe AS
and treated with TAVI between July 2011 and August 2013. Hematological parameters
of the patients were examined prior to the procedure and 24 h, 1 month, and 6
months after TAVI. RESULTS: A statistically significant change in patients' MPV
was detected after TAVI compared to the baseline situation (P: 0.001). While no
statistically significant change was observed on the first day after TAVI, at
discharge, compared to the baseline situation, a statistically significant
decrease was seen 1 month and 6 months after discharge. CONCLUSION: We have
demonstrated a decrease in MPV after surgery compared to the value before
surgery. We have sought to propound the change in MPV as an indication of
endothelial function after TAVI.
PMID- 28425249
TI - Prediction of atopy via total immunoglobulin E levels andskin prick tests in
patients with psoriasis.
AB - BACKGROUND/AIM: Although the etiopathogeneses of psoriasis and atopy appear to be
different, psoriasis has been found to be associated with atopy and atopic
dermatitis. In this study, we aimed to determine the role of atopy by examining
the medical history and clinical and laboratory findings of patients with
psoriasis. MATERIALS AND METHODS: Patients with psoriasis, asthma patients, and
healthy volunteers were included in the study. Serum total immunoglobulin E (IgE)
levels were obtained, and prick tests were administered to all groups. RESULTS:
Psoriatic patients demonstrated percentages of atopy history (21.3%) that were
higher than those of the healthy subjects (15.7%). The median total IgE level in
psoriatic patients was found to be statistically higher than that in the healthy
control group (P > 0.05). With respect to mite positivity, there were
statistically significant differences in the psoriatic (P < 0.05) and asthmatic
groups (P < 0.001) when compared to the healthy control group. CONCLUSION: Our
study is the first to use skin prick tests with psoriatic patients. Skin prick
test sensitivity to mites increased in psoriatic patients, and we believe that
this finding may be useful in protecting psoriatic patients from activation of
psoriasis and in determining the appropriate treatment approach.
PMID- 28425250
TI - Retrospective analysis of maternal, fetal, and neonatal outcomesof intrahepatic
cholestasis of pregnancy at Gazi University.
AB - BACKGROUND/AIM: Maternal, fetal, and neonatal outcomes in parturients with
intrahepatic cholestasis of pregnancy (ICP) have been retrospectively documented.
We aimed to present pregnancy outcomes of parturients with ICP who underwent
delivery. The study was conducted during a 1-year period. MATERIALS AND METHODS:
After ethics committee approval, data from 1 January to 31 December 2015 were
collected to identify parturients with ICP. RESULTS: Ten out of 37 patients
underwent normal spontaneous vaginal delivery (NSVD), and the remaining 27
parturients underwent cesarean section (CS). Five of 27 parturients underwent
nonelective cesarean section, while 22 had elective cesarean delivery. As for
NSVD deliveries, only one parturient received combined spinal and epidural
anesthesia (CSE) for labor. Neuraxial (n = 22 for spinal and n = 1 for CSE) and
general anesthesia (n = 4) rates for CSs were 85% and 15%, respectively.
Approximately 96% of neuraxial anesthesia choices were spinal anesthesia. Nearly
18.5% of CSs were not elective. Adverse outcomes included 2 preterm births, 2
preterm labors, 2 newborns with hepatitis, and one perinatal fetal death.
CONCLUSION: Parturients with ICP who had normal coagulation parameters despite
increased liver enzymes preoperatively underwent cesarean delivery under spinal
anesthesia without complication. Although maternal outcomes were generally
positive, adverse fetal and neonatal outcomes are more likely to occur,
particularly in cases with severe ICP.
PMID- 28425251
TI - Evaluation of plantar pressure distributions in patients with anteriorcruciate
ligament deficiency: preoperative and postoperative changes.
AB - BACKGROUND/AIM: Anterior cruciate ligament (ACL) deficiency results in several
kinematic changes in the lower extremities. The aim of this study is to define
the plantar pressure parameters in ACL-deficient patients and to show the effect
of ACL reconstruction on dynamic plantar pressure. MATERIALS AND METHODS: Forty
patients with unilateral ACL rupture and 40 healthy controls were included in
this study. Dynamic plantar pressures of both groups were recorded by the EMED SF
2 system during level walking. Thirteen of the patients who had ACL
reconstructions with hamstring autografts (HS group) were reevaluated at an
average of 14.5 months following the ACL reconstructions. RESULTS: ACL-deficient
patients had significantly lower hindfoot (P = 0.007) but higher midfoot pressure
values (P = 0.03) on their ipsilateral foot compared to control group subjects.
Ipsilateral hindfoot pressures were also found to be significantly lower than
those of the contralateral foot (P = 0.001). Hindfoot pressure values of the HS
group were increased in postoperative measurements (P = 0.01). CONCLUSION: ACL
deficient patients have altered plantar pressure distributions and ACL
reconstructions restore these changes to normal. Pedobarography might be used as
a practical method for dynamic functional assessment of ACL-deficient patients.
PMID- 28425252
TI - Allergic and autoimmune disorders in families with selective IgA deficiency.
AB - BACKGROUND/AIM: IgA deficiency is the most common human primary immunodeficiency.
The prevalence of allergic disorders and autoimmunity is thought to be increased
in selective IgA deficiency (sIgAD). However, it is currently unclear if these
disorders coincide within these families. We aimed to evaluate the frequency of
allergic and autoimmune disorders in children with sIgAD and their first-degree
relatives (FDRs). MATERIALS AND METHODS: The study included 81 children diagnosed
with sIgAD and 274 of their FDRs. The presence of allergic and autoimmune
disorders was evaluated and serum antithyroglobulin and antithyroid peroxidase
levels were measured in both patients and their first-degree relatives. RESULTS:
The mean age of the patients was 9.9 +/- 3.9 years. Among the patients with
sIgAD, 45.7% of them had at least one allergic disorder and 17.3% of them had at
least one autoimmune disorder. The frequencies of asthma, allergic rhinitis, and
eczema in the FDRs of sIgAD patients were 10.9%, 9.1%, and 7.7%, respectively.
Among their FDRs, 14.6% had autoimmunity, compared to an estimate of 5% in the
general population. CONCLUSION: Increased frequency of allergic and autoimmune
disorders in patients with sIgAD and their FDRs suggests a possible common
predisposing genetic component for sIgAD and autoimmunity in these families.
PMID- 28425253
TI - Association of the CETP gene TaqIB and D442G polymorphisms with essential
hypertension in the Chinese Mongolian population.
AB - BACKGROUND/AIM: This study aimed to explore the associations of the cholesteryl
ester transfer protein (CETP) gene TaqIB and D442G polymorphisms with essential
hypertension (EH). MATERIALS AND METHODS: In this case-control study, 883
hypertensive patients and 1044 normal controls were randomly selected from the
Mongolian population of China. Polymerase chain reaction (PCR) and direct
sequencing of PCR products were used to identify the genotypes. Haplotype
analysis was performed by estimating the haplotype frequencies using the online
SHEsis package. RESULTS: The distribution frequency of the B2-G haplotype was
significantly lower in the EH group than in the control group (0.7% vs. 1.9%, P =
0.001, OR = 0.359 [0.188-0.689]). Subjects with the B2B2 genotype showed
significantly lower levels of total cholesterol (TC) (P < 0.05). When subgrouped
by sex, male subjects with the B2B2 genotype showed significantly increased high
density lipoprotein cholesterol and decreased TC levels (P < 0.05), and those
with the B2 allele showed significantly lower triglyceride levels as compared to
the subjects with the B1B1 homozygote (P < 0.05). CONCLUSION: TaqIB and D442G
polymorphisms of the CETP gene did not independently affect the risk of
developing EH in the Chinese Mongolian population, while the B2-G haplotype
obviously decreased the susceptibility to EH. The B2 allele could alter the blood
lipid level and reduce the risk of developing cardiovascular diseases.
PMID- 28425254
TI - Wheezing, asthma, and atopy in premature infants at 2 years of age.
AB - BACKGROUND/AIM: We aimed to evaluate wheezing, bronchial asthma (BA), and atopy
in premature infants at 2 years of age via a cross-sectional study. MATERIALS AND
METHODS: Premature infants at <37 weeks of gestational age (GA) were assessed for
atopy by skin-prick test and serum immunoglobulin E level at 2 years of age. The
family's and infant's histories of allergy, BA, atopy, and wheezing were obtained
by questionnaire and from hospital records. RESULTS: There were 98 infants, with
mean birth weight (BW) 1517.4 +/- 486.5 g and GA 30.8 +/- 2.9 weeks. The
frequencies of wheezing, asthma, and bronchopulmonary dysplasia (BPD) were 32.7%,
16.3%, and 14.3%, respectively. Skin-prick tests were positive for 11 subjects,
with allergy to cereals for 7 infants, egg for 3, and peanut for 1. Wheezing was
related to GA, BW, respiratory distress syndrome, mechanical ventilation, sepsis,
asphyxia, smoking, antenatal steroid, BA, palivizumab prophylaxis, number of
people in the household, and duration of hospitalization (P < 0.05). Wheezing was
negatively correlated to GA. Family history of BA, smoking, and number of people
in the household were linked to BA (P < 0.05). CONCLUSION: Wheezing was related
to degree of premature birth, but BA was linked to BA in the family and smoking.
Increased gestation should improve the infant's respiratory health up to 2 years
of age.
PMID- 28425255
TI - Aortic valve sclerosis is associated with the extent of coronaryartery disease in
stable coronary artery disease.
AB - BACKGROUND/AIM: Aortic valve sclerosis (AVS) is characterized by lipid deposition
and calcific infiltration on the edge of aortic leaflets without significant
restriction of motion. The SYNTAX Score (SS) is an important method for
evaluating coronary artery disease (CAD). Many studies showed that there is an
important relation between the SS and undesired cardiac outcomes. In our study,
we investigated the correlation between the SS and AVS by including both ACS and
stable CAD cases. MATERIALS AND METHODS: We enrolled 543 patients with CAD who
underwent coronary angiography into this cross-sectional study between September
2013 and September 2014. RESULTS: The study population was divided into two
groups according to SS values above and below 22. Diabetes mellitus (DM)
incidence was greater in the group with high SS values (26.3% vs. 19.2%, P =
0.052.). Left ventricular ejection fraction (LVEF) and glomerular filtration rate
were lower. Low-density lipoprotein cholesterol and triglyceride levels were
lower while platelet counts were higher. In multivariate analysis, for the stable
coronary artery group AVS existence, platelet count, LVEF value, and chronic
obstructive pulmonary disease were found as independent predictors. CONCLUSION:
Our study results demonstrated that AVS is significantly associated with the
complexity of CAD, especially in patients with stable CAD. This study provides
new information regarding the role of AVS in CAD complexity.
PMID- 28425256
TI - Predictive values of plasma KL-6 in bronchopulmonary dysplasia in preterm
infants.
AB - BACKGROUND/AIM: It has been suggested that plasma KL-6 increases in premature
infants with bronchopulmonary dysplasia (BPD). We aimed to evaluate the
predictive values of KL-6 in BPD. MATERIALS AND METHODS: The study was performed
in preterm neonates with birthweight <=1500 g and gestational age <=32 weeks.
Plasma KL-6 levels were measured on postnatal days 1, 7, and 14. RESULTS: BPD was
identified in eight of the 28 study infants. On postnatal days 1 and 7, plasma KL
6 levels were similar in infants with BPD [on day 1: 8.9 (7.5-17.8) U/mL and on
day 7: 16.8 (10.5-47.7) U/mL] and without BPD [on day 1: 10.8 (9.4-17.2) U/mL and
on day 7: 12.9 (5.8-19.3) U/mL] (P = 0.38 and P = 0.13, respectively). On day 14,
KL-6 levels were significantly higher in infants with BPD [155.2 (15.3-545.6)
U/mL] than they were in infants without BPD [7.9 (7.7-15.6) U/mL] (P = 0.001).
The best predictor was KL-6 levels on postnatal day 14 (area under the ROC curve
= 0.88; range 0.75-1.0; P = 0.002). At this point, KL-6 level of 59.7 U/mL showed
a specificity of 90.0% and negative predictive value of 85.7% for BPD.
CONCLUSION: High plasma KL-6 levels on postnatal day 14 in premature infants may
predict the development of BPD.
PMID- 28425257
TI - Role of hygienic factors in the etiology of allergic disorders in children.
AB - BACKGROUND/AIM: We investigated the role of body flora and chronic inflammatory
infections in the etiology of allergic disorders in Turkish children. MATERIALS
AND METHODS: Forty pediatric asthma patients with positive skin prick tests and
40 age-matched healthy subjects with negative skin prick tests were enrolled in
this cross-sectional study. Serum H. pylori IgG, viral hepatitis serology, IL-10,
and TGF-beta levels were measured. Stool and throat cultures were taken and
tested for occurrence of microorganisms. RESULTS: A significantly higher
percentage of nonatopic subjects tested positive for anti-H. pylori antibodies
compared to atopic subjects (60% vs. 20%). Serum IL-10 levels were also
significantly higher in nonatopic subjects. No significant differences in direct
microscopy and culture specimens of stools were observed. Examination of throat
flora showed significantly higher occurrences of Neisseria and beta-hemolytic
Streptococcus in nonatopic subjects, but higher occurrences of gram-positive
bacilli in atopic subjects. CONCLUSION: Higher prevalence of anti-H. pylori
antibody and higher serum levels of IL-10 in nonatopic subjects suggest that
chronic infection and inflammation may protect against atopic disease. Higher
occurrences of Neisseria and beta-hemolytic Streptococcus in throat cultures from
nonatopic subjects are novel findings that lend further support to the hygiene
hypothesis.
PMID- 28425258
TI - Assessment of developmental and radiological long-term outcomeof children with
surgically treated midgut volvulus.
AB - BACKGROUND/AIM: The aim is to evaluate the long-term outcome of asymptomatic
patients who underwent surgical correction for midgut volvulus. MATERIALS AND
METHODS: Seven patients managed surgically for midgut volvulus in the last 3
years were included. Demographic features, symptoms at presentation, diagnoses,
surgical procedures, and complications were recorded. Patients were then
contacted for follow-up and evaluation of long-term outcomes. General physical
conditions, anthropometric parameters, feeding habits, and defecation histories
were evaluated. Laboratory examinations were performed. Color Doppler
ultrasonography (CDUS) was performed to evaluate blood flow in the superior
mesenteric artery (SMA). RESULTS: In total, seven patients were identified. The
median age at admission was 3 days (0-90 days). Mean age at follow-up was 17 +/-
2 months. Growth parameters were normal in all cases. Four patients had low
levels of ferritin and transferrin saturation. One patient had microcytic anemia.
Another patient had low serum zinc level. One patient who had ileal resection had
a high level of steatorrhea in stool examination. In CDUS, SMA blood flow volume
was low in all cases. Peak-systolic velocity and resistance index were low in all
but one case. CONCLUSION: Despite uneventful postoperative courses, all patients
operated on for midgut volvulus showed mild laboratory changes and decreased
blood flow in the SMA in long-term follow-up.
PMID- 28425260
TI - The efficacy of microphototherapy with a MedLight CupCUBEGrimed device in
psoriatic patients with localized lesions.
AB - BACKGROUND/AIM: Psoriasis is a chronic skin disease. To reduce side effects
associated with current treatment modalities, new treatment methods are required.
Some clinicians have begun to use microphototherapy to treat psoriatic patients
with a limited number of lesions (lesions affecting <10% of the body surface
area). MATERIALS AND METHODS: Microphototherapy is indicated in patients whose
lesions persist despite systemic and topical treatment or when such treatment is
contraindicated. Our study aimed to evaluate the efficacy of microphototherapy in
psoriasis patients with localized lesions. Patients in this unblinded and
prospective study were treated three times a week for 50 sessions using a
MedLight CupCUBE Grimed microphototherapy device that emits an ultraviolet B
(UVB) spectrum. RESULTS: Forty-five lesions in 23 psoriatic patients were
treated. Treatment outcome was evaluated based on the Psoriasis Severity Index
(PSI). PSI scores decreased significantly during the treatment. CONCLUSION: The
MedLight CupCUBE Grimed microphototherapy device was effective for the treatment
of psoriasis patients with localized lesions. The device can administer UVB
radiation to involved regions while protecting uninvolved regions and minimizing
radiation dose. However, having to be administered by experienced technicians and
the long time required for each treatment session are disadvantages of the
technique.
PMID- 28425259
TI - Analysis of FANCC gene mutations (IVS4+4A>T, del322G, and R548X)in patients with
Fanconi anemia in Pakistan.
AB - BACKGROUND/AIM: Fanconi anemia (FA) is an autosomal recessive disease determined
by mutations in at least 16 genes, with distinct distributions in different
populations. To the best of our knowledge, there are no reports regarding the
molecular basis of the disease in FA patients in Pakistan. The current study
aimed to determine the frequency of FANCC gene mutations, i.e. IVS4+4A>T,
del322G, and R548X, in FA patients. MATERIALS AND METHODS: Genomic DNA was
obtained from 36 FA patients. All samples were analyzed by polymerase chain
reaction and restriction fragment length polymorphism techniques. RESULTS:
Mutation IVS4+4A>T was identified in 26 (72.2%) patients. It was homozygous in 6
and heterozygous in 20 patients. Del322G and R548X were found with the following
prevalences: del322G, 5.6%, and R548X, 5.6%. Patients with these two mutations
were compound heterozygotes having concomitant IVS4+4A>T mutation. CONCLUSION:
These results suggest that mutation IVS4+4A>T is the most prevalent mutation in
our group of patients. This analysis of Pakistani patients also suggests that
there is no significant difference between IVS4+4A>T homozygotes and the rest of
the patients with regard to severity of clinical phenotype.
PMID- 28425261
TI - Central line-associated blood stream infections: characteristics and risk factors
for mortality over a 5.5-year period.
AB - BACKGROUND/AIM: Central line-associated bloodstream infections (CLABSIs) are
associated with substantial morbidity and mortality and the infection rates vary
in a wide range1397645907(high: 62.5%; low: 20%) in developing countries. We
aimed to investigate the characteristics and the risk factors for mortality in
patients with CLABSIs in intensive care units (ICUs) and provide the relevant
data. MATERIALS AND METHODS: The electronic medical records database and file
records obtained through active surveillance by an infection control committee of
a hospital were screened to identify patients with CLABSIs hospitalized from
January 2008 through July 2013. RESULTS: A total of 166 CLABSI episodes in 158
patients out of 17,553 on 38,562 catheter and 94,512 hospitalization days were
evaluated. The infection developed in catheterized patients at a median of 14
days (range 2-88), and the highest infection rate with 13.4% (n = 20) was the
femoral region among the places where the catheter was inserted. Of the patients
catheterized, 54.4% survived whereas 45.6% died. In patients having Candida
infection, the mortality was significantly higher. High APACHE II scores and
Candida infections were found to be significant risk factors associated with
mortality. CONCLUSION: APACHE II scores and bloodstream infection with Candida
species were the most powerful predictors of mortality. In ICU practice, health
care givers must consider the emerging role of Candida for both invasiveness and
mortality.
PMID- 28425262
TI - Copeptin levels in carbon monoxide poisoning.
AB - BACKGROUND/AIM: The aim of this study is to identify the copeptin levels in
patients presenting with carbon monoxide (CO) poisoning to the emergency
department and to investigate its correlation with the neurological effects.
MATERIALS AND METHODS: The study group consisted of patients presenting with CO
poisoning and carboxyhemoglobin levels >10%. Blood samples for copeptin levels
were obtained twice, first at presentation then at the fourth hour of
observation. The data were analyzed using SPSS 16 for Windows. RESULTS: The
median copeptin levels of the patient group were identified as 0.63 (0.39-1.06)
ng/mL at hour 0 and 0.41 (0.31-0.49) at hour 4. The copeptin levels of the
control group were 0.34 (0.25-0.42) ng/mL and were significantly lower than those
of the patient group (P < 0.000). According to our results, 0.345 ng/mL for
plasma copeptin level as the best cut-off level may be used with sensitivity of
94.0% and specificity of 60%. The copeptin levels at hour 0 were statistically
significantly higher in the neurologically affected patients than those not
affected (P < 0.001). CONCLUSION: In this study it was shown that blood copeptin
levels increase in patients presenting to the emergency department with CO
poisoning.
PMID- 28425263
TI - Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody
enhances antitumor efficacy in renal cell carcinoma-bearing mice.
AB - BACKGROUND/AIM: Dendritic cell-based vaccine therapy for renal cell carcinoma is
effective but requires improvement. Here we explored whether combination therapy
with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor
efficacy in renal cell carcinoma-bearing mice. MATERIALS AND METHODS: Balb/c mice
were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On
day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated
or were treated with Renca tumor lysate-pulsed dendritic cells (i.e. dendritic
cell-based vaccine), anti-CD69 antibody, or a combination of Renca tumor lysate
pulsed dendritic cells with anti-CD69 antibody. The mice were sacrificed on day
28. Tumor volume was measured for analysis of antitumor efficacy. Spleens were
excised to evaluate antitumor immunological responses by measuring the
proliferation and activation of T cells, which have the capacity to recognize and
destroy tumor cells. RESULTS: Combination treatment with Renca tumor lysate
pulsed dendritic cells and anti-CD69 antibody resulted in significant decreases
in tumor volume and significant increases in T-cell proliferation and activity,
compared with no treatment or either treatment alone. CONCLUSION: These findings
indicate that anti-CD69 antibody can potentiate antitumor efficacy of dendritic
cell-based vaccine. The augmented therapeutic efficacy conferred by the
combination therapy may be associated with increased T-cell proliferation and
activity.
PMID- 28425264
TI - Rho/rho-kinase signalling in chronically alcohol-fed mice.
AB - BACKGROUND/AIM: The effects of chronic ethanol consumption on male sexual
function are debateable, and its effects on the Rho/Rho-kinase pathway are
unknown. Therefore, we investigated smooth muscle reactivity and Rho/Rho-kinase
signalling in the corpus cavernosum of ethanol-fed mice. MATERIALS AND METHODS:
Ethanol was added to drinking water at 5% concentration in the first 2 days with
5% increment every subsequent 2 days, up to a final concentration of 20% for 45
days. Corpora cavernosa were isolated and a cumulative dose-response curve to
phenylephrine was obtained. Acetylcholine (10-6 M), electrical field stimulation
(EFS, 40 V, 8-16 Hz) and Y-27632 (10-6-10-5 M)-induced relaxations were compared
in the control and ethanol groups. RESULTS: Blood ethanol levels in the control
and ethanol-treated mice were 1.5 +/- 0.3 mg/dL and 37.4 +/- 4.1 mg/dL (P <
0.001), respectively. Phenylephrine-induced contractile responses were
potentiated in the ethanol group, with pD2 values of 4.92 +/- 0.18 and 5.71 +/-
0.21 (P < 0.01) in the corpus cavernosum obtained from control and alcohol-fed
mice, respectively. The relaxant responses to acetylcholine and EFS, but not Y
27632, were significantly augmented in the corpus cavernosum obtained from
ethanol-treated mice. However, expression and activation of Rho-kinase remained
unchanged in the alcohol group. CONCLUSION: Ethanol drinking may increase
sensitivity to both vasoconstrictors and vasodilators in the mouse corpus
cavernosum without any alteration in Rho/Rho-kinase signalling.
PMID- 28425265
TI - Effects of Ankaferd BloodStopper on dermal healing in diabetic rats.
AB - BACKGROUND/AIM: Diabetes mellitus inhibits wound-induced angiogenesis, impairs
the wound healing process, and leads to the development of chronic wounds.
Ankaferd BloodStopper (ABS) is a new and promising local haemostatic agent.
Although the mechanism of ABS-mediated haemostasis is well established, little is
known about the associated histological and biochemical tissue reactions. The aim
of this study was to evaluate the effects of this new-generation local
haemostatic agent on short-term soft-tissue healing in streptozotocin (STZ)
treated rats. MATERIALS AND METHODS: The 24 Wistar albino rats used in this study
were divided into STZ-treated (STZ, n = 12) and nontreated groups (control, n =
12). Four days prior to surgery, rats in the STZ group were subcutaneously
administered 60 mg/kg STZ intraperitoneally, while rats in the control group were
administered 1 mL saline/kg. An incision was made in the dorsal dermal tissue of
all rats, and either ABS or no haemostatic agent (NHAA) was applied to the wound
before suturing. All of the rats were euthanised on postoperative day 4. Blood
and skin samples were evaluated biochemically and histologically. RESULTS: The
results showed that STZ treatment impaired soft-tissue healing, assessed by
measuring glutathione and lipid peroxidation levels. Moreover, while good
histological results were obtained in the control group treated with ABS, there
were fewer benefits in the STZ-treated group. CONCLUSION: ABS's benefits in the
control group seemed to lose their effectiveness under STZ medication.
PMID- 28425266
TI - Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated
rats: implications for chronic migraine.
AB - BACKGROUND/AIM: Chronic migraine is a common debilitating disease with limited
treatment options. We aimed to develop a novel model for chronic migraine by
ligating the nasociliary nerve (NCL) and administering nitroglycerin (NTG) to
exacerbate acute headache attacks. MATERIALS AND METHODS: Exacerbation of the
headache was induced by NTG (10 mg/kg, subcutaneously) administered to male
Wistar rats (n = 36) 14 days following unilateral NCL. Cutaneous and cold
allodynia was tested using Von Frey (VF) filaments and acetone, respectively.
Elevated plus maze (EPM) results and c-fos immunoreactivity of TNC were
investigated. RESULTS: NTG administration significantly decreased VF threshold
values only in the nasociliary nerve (NCN) territory and the ipsilateral forepaw
(P = 0.0001, P = 0.02). Cold allodynia developed in bilateral NCN territories (P
= 0.013). The number/rate of entrance to open arms in the EPM was significantly
decreased in NCN-ligated rats (P = 0.042, P = 0.035). Immunohistochemistry
disclosed significantly increased c-fos-positive neurons in ipsilateral brainstem
TNC compared to the contralateral side (brain stem LI ipsilateral 25.4 +/- 4.7,
contralateral 11.8 +/- 1.9, P < 0.05) in chronic NCN-ligated rats exposed to
acute NTG. CONCLUSION: The presented model provides a valid chronic migraine
model relevant to humans, as NTG challenge in chronic NCL rats generated
lateralized headache with cephalic and extracephalic allodynia, altered cold
sensitivity, anxiety, and neuronal activation in the nociceptive laminae of
brainstem trigeminal pain nuclei.
PMID- 28425267
TI - Modifications of mice gut microflora following oral consumption ofLactobacillus
acidophilus and Bifidobacterium bifidum probiotics.
AB - BACKGROUND/AIM: Thirty male BALB/c mice were equally divided into three groups:
control, L. acidophilus, and B. bifidum for the assessment of the probiotics'
stability in the gut microflora. MATERIALS AND METHODS: First, the gut microflora
of the mice was checked every 3 days (days 3, 6, 9, and 12) without probiotic
consumption, and then the mice were daily given orally 1.5 g of probiotics in 30
cc of drinking water. The consumption of probiotics was then stopped for recovery
and then the consumption continued for 5 months. RESULTS: On day 9 after the
consumption of the probiotics, L. acidophilus and B. bifidum were significantly
increased from 4% to 83% and from 1% to 61%, respectively. L. acidophilus count
showed no significant decrease at the end of 5 months compared to day 9 of
probiotic consumption (74%), but B. bifidum count was dramatically decreased to
45% and 36% at the end of 1 and 5 months, respectively. CONCLUSION: Our results
revealed that, unlike B. bifidum, the amount of L. acidophilus remained almost
unchanged in the long term, indicating more stability of L. acidophilus than B.
bifidum in the gut microflora.
PMID- 28425268
TI - Efficient production of nanobodies against urease activity ofHelicobacter pylori
in Pichia pastoris.
AB - BACKGROUND/AIM: Helicobacter pylori is a major health problem. One of the
therapeutic approaches is administration of antibody against H. pylori. The
methylotrophic Pichia pastoris is a suitable host for expression of recombinant
antibody fragments. The aims of this study were the expression and the evaluation
of camelid nanobody in the yeast Pichia pastoris. MATERIALS AND METHODS: The
camelid-derived heavy-chain antibody (nanobody) against the UreC subunit of
urease from H. pylori was subcloned in the pPink-HC shuttle vector and
transferred into Escherichia coli TOP10. After digestion and purification, the
shuttle vector was transformed in the PichiaPink expression system. The
expression was evaluated in an in vitro system. RESULTS: The yield of the
nanobody expressed in P. pastoris was estimated to be 5 mg/L as compared to 2
mg/L expressed by E. coli. The nanobody was purified and binding affinity to the
UreC antigen was evaluated using ELISA. Neutralization abilities of the two
nanobodies expressed in yeast and E. coli were compared. The yeast-expressed
nanobody specifically detected recombinant UreC and inhibited urease activity
with high efficiency. CONCLUSION: The results suggest attribution of the enhanced
quality and quantity of the nanobody produced in P. pastoris to better
posttranslational modification and folding in the yeast cell.
PMID- 28425269
TI - Evaluation of cytotoxic, membrane, and DNA damaging effects of Thymus revolutus
Celak essential oil on different cancer cells.
AB - BACKGROUND/AIM: In this study, we evaluated Thymus revolutus Celak essential oil
and its two main constituents, gamma-terpinene and p-cymene, as potential
oxidative agents against lung cancer and epidermoid carcinoma cells. MATERIALS
AND METHODS: Cell viability assessment was made by CellTiter-Blue1397904493 cell
viability and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay after treatment with 5-600 MUg/mL concentrations of essential oil, gamma
terpinene, and p-cymene. Malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels
in parental H1299, epirubicin-resistant (drug-resistant) H1299, A549, and A431
cells were also assayed after essential oil, gamma-terpinene, and p-cymene had
been administered for 24 h. Glutathione S-transferase (GST), glutathione
peroxidase (GPx), glutathione reductase (GRx), and glucose 6-phosphate
dehydrogenase (G6PD) activities were determined. RESULTS: Parental H1299 cells
were found to be more sensitive to the cytotoxic effects of all compounds. While
A431 cells had the highest membrane damage, which was caused by essential oil
(IC50 and IC70), A549 cells had the highest DNA damage at IC50 and IC70 p-cymene
concentrations. G6PD, GST, GRx, and GPx enzyme activities of cells, which
increased against these compounds, depended on concentrations, incubation times,
and antioxidant capacities of the cells. CONCLUSION: This study suggests that
different cancer cells showed different cellular responses against potential
antitumor and prooxidative effects of the essential oil and its two main
constituents.
PMID- 28425270
TI - A new angiogenesis prognostic index with VEGFA, PlGF, and angiopoietin1 predicts
survival in patients with advanced gastric cancer.
AB - BACKGROUND/AIM: The role of angiogenic factors in gastric cancer is not clear. We
aimed to assess the role of vascular endothelial growth factor A (VEGFA),
angiopoietin 1 (Ang-1), and placental growth factor (PlGF) in the prognosis of
patients with advanced gastric cancer. MATERIALS AND METHODS: Thirty consecutive
patients treated with a modified DCF (docetaxel, cisplatin, and fluorouracil)
regimen were included in the study. The plasma VEGFA, Ang-1, and PlGF levels of
the patients before treatment and following two cycles of chemotherapy were
measured and evaluated as prognostic factors. RESULTS: Poor performance status
and lower Ang-1 levels were correlated with poor overall survival (OS). No
significant correlation between VEGFA or PlGF and OS was found. An angiogenesis
prognostic index (API) based on the levels of VEGFA, Ang-1, and PlGF was found to
be highly correlated with OS. Performance status and API were found as
independent prognostic factors for OS. Furthermore, a decrease in VEGFA by 25%
from the pretreatment level was also found as a prognostic factor for OS
independent of response to DCF regimen. CONCLUSION: Our results support the use
of the new API including VEGFA, Ang-1, and PlGF levels in patients with advanced
gastric cancer as a predictor of survival.
PMID- 28425271
TI - Molecular characteristics and antibiotic resistance of Acinetobacter
baumanniibeta-lactamase-producing isolates, a predominance of intrinsic blaOXA
51, and detection of TEM and CTX-M genes.
AB - BACKGROUND/AIM: The aim of this study was to determine the molecular
characteristics and antibiotic resistance of 13 (10 inpatient and three
outpatient) Acinetobacter baumannii beta-lactamase-producing isolates collected
in Bosnia and Herzegovina between December 2009 and May 2010. MATERIALS AND
METHODS: Susceptibility testing was performed by disk diffusion and broth
microdilution methods. The modified Hodge and combined disk test with
EDTA/phenylboronic acid was used to screen for carbapenemase production.
Production of extended spectrum beta-lactamases (ESBLs) was determined by double
disk synergy test. PCR was used to detect blaESBL/blacarb genes. RESULTS: Ten
(22.2%) inpatient and three (13.6%) outpatient isolates produced beta-lactamases,
ESBLs, or oxacillinases. More than 50% of the isolates showed multidrug
resistance. Resistance rates to gentamicin and ciprofloxacin of the inpatients
and outpatients were 80.0%, 60.0%, 75.0%, and 25.0%, respectively. MICs of
carbapenems for resistant isolates ranged from 32 to >256 MUg/mL. All imipenem
resistant Acinetobacter baumannii strains contained blaOXA-51. Three of the 10
inpatient isolates and one outpatient isolate containing blaOXA-51 additionally
produced other beta-lactamases (TEM/CTX-M/OXA-1). None of the inpatient or
outpatient isolates were positive for other carbapenemases, especially acquired
oxacillinases (blaOXA-23/blaOXA-24/blaOXA-58/blaOXA-143). CONCLUSION: Production
of blaOXA-51 presents an emerging threat in imipenem-resistant Acinetobacter spp.
from Bosnia and Herzegovina.
PMID- 28425272
TI - Effect of transfusion of washed red blood cells on serumpotassium level in
hemodialysis patients.
AB - BACKGROUND/AIM: This study aimed to compare washed red blood cell (WRBC)
transfusion versus nonwashed RBC (NWRBC) transfusion in terms of posttransfusion
potassium levels in dialysis patients on a day when the patient did not receive
dialysis. MATERIALS AND METHODS: The patients were randomly assigned into two
groups, i.e. those receiving WRBCs (n = 21) and those receiving NWRBCs (n = 17).
Both groups received one unit of RBCs. Serum potassium and sodium levels were
measured before and at the 1st, 2nd, 3rd, 4th, and 6th hours after transfusion.
RESULTS: In the WRBC group, the changes in the serum potassium levels at the 3rd,
4th, and 6th hours after transfusion were significant compared with
pretransfusion levels. In the serum potassium levels mean decreases by 0.38 +/-
0.57 mEq/L at the 3rd hour (P = 0.006), by 0.32 +/- 0.47 mEq/L at the 4th hour (P
= 0.005), and by 0.32 +/- 0.51 mEq/L at the 6th hour (P = 0.009) after
transfusion were significant compared with the pretransfusion levels. CONCLUSION:
Although nonwashed RBC transfusion does not change serum potassium levels, washed
RBC transfusion significantly reduces serum potassium levels. Washed RBC
transfusion is considered to be safer in hemodialysis patients with hyperkalemia
and anemia.
PMID- 28425273
TI - Radiation therapy for biliary tract tumors: the joint experience of three
centers.
AB - BACKGROUND/AIM: This study presents the joint experience of three centers in the
treatment of patients with biliary tract tumors with radiation therapy (RT).
MATERIALS AND METHODS: The records of 27 patients were retrospectively reviewed.
All of the patients who had undergone surgical resection received postoperative
adjuvant RT, whereas all of the patients who had not undergone a surgical
resection received RT with palliative intent. Twenty patients with adequate
performance status were treated with RT and chemotherapy, while the remaining
seven patients were treated with RT alone. RESULTS: Follow-up ranged from 1 to 44
months. Local control was not achieved in 10 out of 11 patients who had received
RT with palliative intent. Systemic failure was observed in eight patients at 5
to 16 months. Fifteen patients died due to disease-related causes at 1 to 22
months. At 2 years, overall survival was 33% and disease-free survival was 19%. A
surgical resection with curative intent predicted improved local failure-free
survival and improved disease-free survival. CONCLUSION: Since local recurrence
is still the leading cause of failure following postoperative RT and the outcome
following palliative RT is far from satisfactory, the indications, the target
volume, and the doses for RT should be reconsidered.
PMID- 28425274
TI - Profile of POT1 as telomerase shelterin component discriminatesbetween cervical
cancer and normal cervical cells.
AB - BACKGROUND/AIM: Telomerase activity is influenced by hTERT transcriptional
regulation, shelterin, and posttranscriptional alternative splicing. Telomerase
shelterin such as POT1 is highly correlated with various cancers. However, the
profile of POT1 in cervical cancer has not been clearly identified. Therefore, it
is important to identify its profile in cervical cancer biopsy tissue and normal
cervical smears. MATERIALS AND METHODS: Biopsy tissue of cervical cancer patients
and normal cervical smears were characterized using SDS-PAGE and western blot.
Sixteen biopsy tissues of cervical cancer patients and 15 normal cervical smears
were measured for POT1 level using ELISA. RESULTS: The inline band at 70 kDa
indicated that all samples had protein that was identified as POT1. Western blot
showed that telomerase antibody only recognized POT1 in biopsy tissue of cervical
cancer patients. There was a significant difference (P = 0.01) in POT1 level
between biopsy tissue of cervical cancer patients and normal cervical smears.
CONCLUSION: POT1 was identified at 70 kDa in biopsy tissue of cervical cancer
patients and its level was higher than that in normal cervical smears. The high
level of POT1 in the biopsy tissue of cervical cancer patients showed the
influence of this shelterin component in cervical carcinogenesis and also cell
immortalization.
PMID- 28425275
TI - Associations between obesity and the radiographic phenotype in knee
osteoarthritis.
AB - BACKGROUND/AIM: Investigation of the association between obesity and the
distinction of radiographic patterns in knee osteoarthritis. MATERIALS AND
METHODS: Seven hundred and thirty-four women underwent weight-bearing antero
posterior knee radiography. Osteophytes and joint space narrowing (JSN) were
graded according to the OARSI atlas. Each subject was assigned to one of the
following groups with respect to the maximum score: osteophyte-dominant,
indeterminate, JSN-dominant, and radiographically normal. RESULTS: Obese patients
had a significantly more frequent osteophyte-dominant pattern compared to
nonobese subjects (74.5% and 38%, respectively, P < 0.001). Logistic regression
analysis demonstrated that obesity had a stronger association with an osteophyte
dominant pattern compared to a JSN-dominant pattern (OR and 95% CI = 7.16 (3.15
16.26) and 1.63 (0.96-2.78), respectively). Age had a very weak effect on the
distinction to an osteophyte-dominant pattern and no effect on JSN dominance (OR
and 95% CI = 1.1 (1.06-1.15) and 1.02 (0.99-1.05), respectively). CONCLUSION:
There might be an association between obesity and the radiographic phenotype in
patients with knee osteoarthritis. The findings suggest that the association
between obesity and the osteophyte formation is stronger than that of JSN.
PMID- 28425276
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28425277
TI - "Zombie" Outbreak Caused by Synthetic Cannabinoid.
PMID- 28425278
TI - Screening for Colorectal Neoplasia.
PMID- 28425279
TI - Screening for Colorectal Neoplasia.
PMID- 28425280
TI - Large-Scale Synthesis of Monodisperse UiO-66 Crystals with Tunable Sizes and
Missing Linker Defects via Acid/Base Co-Modulation.
AB - Beyond their pore structures and surface chemistry, precise controls over other
attributes of metal-organic frameworks (MOFs) such as shapes, sizes, and defects
are also favorable to their fundamental studies and applications but still remain
challenging. Herein, we reported an acid/base co-modulation strategy to the large
scale synthesis of monodisperse UiO-66 crystals with acetic acid for modulating
crystal shape and with triethylamine (TEA) as a base for controlling the
nucleation of crystallization and tuning the formation of missing linker defects
via promoting presumably the singe deprotonation of terephthalic acid linkers.
The obtained monodisperse MOF crystals have a well-defined octahedral shape,
tunable sizes ranging from ~500 nm to ~2 MUm, and high thermal stability. Their
assembled-monolayers are responsive to methanol vapor with the crystal size
dependent and defect-relevant sensing performances.
PMID- 28425281
TI - Hybridized C-O-Si Interface States at the Origin of Efficiency Improvement in
CNT/Si Solar Cells.
AB - Despite the astonishing values of the power conversion efficiency reached, in
just less than a decade, by the carbon nanotube/silicon (CNT/Si) solar cells,
many doubts remain on the underlying transport mechanisms across the CNT/Si
heterojunction. Here, by combining transient optical spectroscopy in the
femtosecond timescale, X-ray photoemission, and a systematic tracking of I-V
curves across all phases of the interlayer SiOx growth at the interface, we grasp
the mechanism that adequately preserves charge separation at the junction,
hindering the photoexcited carrier recombination. Moreover, supported by ab
initio calculations aimed to model the complex CNT-Si heterointerface, we show
that oxygen-related states at the interface act as entrapping centers for the
photoexcited electrons, thus preventing recombination with holes that can flow
from Si to CNT across the SiOx layer.
PMID- 28425282
TI - Mechanical Force Sensitive Acrylic Latex Coating.
AB - We prepared force sensitive acrylic latex coatings by covalently incorporating
spiropyran mechanophore. The acrylic latexes were obtained through emulsion
copolymerization of butyl acrylate (BA), methyl methacrylate (MMA) with
vinyltriethoxysilane (VTES) as interparticle cross-linker, and (1'-(2
(methacryloyloxy)ethyl)-3',3'-dimethylspiro[chromene-2,2'-indolin]-6-yl)methyl
methacrylate) (SP) as intraparticle cross-linker. The latexes of P(BA-co-MMA-co
SP-co-VTES) were subsequently cast onto Teflon-coated surface to form latex
coatings. The condensation of hydrolyzed VTES provided interparticle cross
linking and improved mechanical properties of the formed thin films.
Intraparticle cross-linker SP endowed the coatings with mechanoreponsiveness. The
mechanoactivation of SP-containing latex films was demonstrated. Increasing the
content of intra-cross-linker SP resulted in higher stress sensitivity and lower
critical stress required for mechanoactivation. Increasing the content of
interparticle cross-linker VTES resulted in higher critical stress for SP
mechanoactivation but had little effect on the stress sensitivity. Tg and
operation temperature also showed significant effect on mechanoactivation. Slower
strain rate allowed for higher SP-to-MC conversion. This work represents the
first example of mechanochromic acrylic latexes and provides insight into the
design of force sensitive and self-reporting polymer coatings.
PMID- 28425283
TI - Total Synthesis of (-)-Angiopterlactone B.
AB - An enantioselective total synthesis of (-)-angiopterlactone B has been
accomplished in four steps. The synthesis features a proposed biomimetic domino
ring-contraction/oxa-Michael/Michael dimerization sequence, forming three new
bonds, two new rings, and three new contiguous stereogenic centers in a single
step. It has been determined that the originally proposed absolute configuration
of natural (+)-angiopterlactone B needs revision. This reveals that
angiopteroside, a known glycoside natural product, is the likely biosynthetic
precursor to (+)-angiopterlactone B.
PMID- 28425284
TI - pH Triggered Size Increasing Gene Carrier for Efficient Tumor Accumulation and
Excellent Antitumor Effect.
AB - High efficiency and serum resistant capacity are important for gene carrier in
vivo usage. In this study, transfection efficiency and cell toxicity of
polyethylenimine (PEI) (branched, Mw = 25K) was remarkably improved, when mixed
with polyanion (polyethylene glycol-polyglutamic acid (PEG-PLG) or polyglutamic
acid (PLG)). Different composite orders of PEI, polyanion, and gene, for example,
PEI is first complexed with DNA, and then with polyanion, or PEI is first
complexed with polyanion, and then with DNA, were studied. Results showed that
only the polyanion/PEI complexes exhibited additional properties, such as
decreased pH, resulting in increased particle size, as well as enhanced serum
resistance capability and improved tumor accumulation. The prepared gene carrier
showed excellent antitumor effect, with no damage on major organs, which is
suitable for in vivo gene antitumor therapy.
PMID- 28425285
TI - Directed Evolution of Carbonyl Reductase from Rhodosporidium toruloides and Its
Application in Stereoselective Synthesis of tert-Butyl (3R,5S)-6-Chloro-3,5
dihydroxyhexanoate.
AB - tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is a key
intermediate of atorvastatin and rosuvastatin synthesis. Carbonyl reductase
RtSCR9 from Rhodosporidium toruloides exhibited excellent activity toward tert
butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH). For the activity of
RtSCR9 to be improved, random mutagenesis and site-saturation mutagenesis were
performed. Three positive mutants were obtained (mut-Gln95Asp, mut-Ile144Lys, and
mut-Phe156Gln). These mutants exhibited 1.94-, 3.03-, and 1.61-fold and 1.93-,
3.15-, and 1.97-fold improvement in the specific activity and kcat/Km,
respectively. Asymmetric reduction of (S)-CHOH by mut-Ile144Lys coupled with
glucose dehydrogenase was conducted. The yield and enantiomeric excess of (3R,5S)
CDHH reached 98 and 99%, respectively, after 8 h bioconversion in a single batch
reaction with 1 M (S)-CHOH, and the space-time yield reached 542.83 mmol L-1 h-1
g-1 wet cell weight. This study presents a new carbonyl reductase for efficient
synthesis of (3R,5S)-CDHH.
PMID- 28425286
TI - Enantioselective Spirocyclopropanation of para-Quinone Methides Using Ammonium
Ylides.
AB - The use of Cinchona alkaloid-based chiral ammonium ylides allows for the first
highly enantioselective and broadly applicable spirocyclopropanation reactions of
para-quinone methides. This strategy provides a straightforward protocol toward
the chiral spiro[2.5]octa-4,7-dien-6-one skeleton, which is a frequently found
structural motif in important biologically active molecules.
PMID- 28425287
TI - Vertical Charge Transfer and Lateral Transport in Graphene/Germanium
Heterostructures.
AB - Heterostructures consisting of two-dimensional (2D) materials and conventional
semiconductors have attracted a lot of attention due to their application in
novel device concepts. In this work, we investigated the lateral transport
characteristics of graphene/germanium heterostructures and compared them with the
transport properties of graphene on SiO2. The heterostructures were fabricated by
transferring a single layer of graphene (Gr) onto a lightly doped germanium (Ge)
(100) substrate. The field-effect measurements revealed a shift in the Dirac
voltage of Gr on the Ge substrates compared to that of the Gr on SiO2. Transfer
length model measurements show a significant difference in the sheet resistance
of Gr on Ge compared to that of the Gr on SiO2. The results from the electrical
and structural characterization suggest that a charge transfer in the order of
1012 cm-2 occurs between Gr and Ge resulting in a doping effect in the graphene
sheet. A compact electrostatic model extracted the key electronic properties of
the Gr/Ge interface. This study provides valuable insights into the electronic
properties of Gr on Ge, which are vital to the development of novel devices based
on mixed 2D and 3D structures.
PMID- 28425288
TI - Tracking Nitrogen Sources, Transformation, and Transport at a Basin Scale with
Complex Plain River Networks.
AB - This research developed an innovative approach to reveal nitrogen sources,
transformation, and transport in large and complex river networks in the Taihu
Lake basin using measurement of dual stable isotopes of nitrate. The spatial
patterns of delta15N corresponded to the urbanization level, and the nitrogen
cycle was associated with the hydrological regime at the basin level. During the
high flow season of summer, nonpoint sources from fertilizer/soils and
atmospheric deposition constituted the highest proportion of the total nitrogen
load. The point sources from sewage/manure, with high ammonium concentrations and
high delta15N and delta18O contents in the form of nitrate, accounted for the
largest inputs among all sources during the low flow season of winter. Hot spot
areas with heavy point source pollution were identified, and the pollutant
transport routes were revealed. Nitrification occurred widely during the warm
seasons, with decreased delta18O values; whereas great potential for
denitrification existed during the low flow seasons of autumn and spring. The
study showed that point source reduction could have effects over the short-term;
however, long-term efforts to substantially control agriculture nonpoint sources
are essential to eutrophication alleviation for the receiving lake, which
clarifies the relationship between point and nonpoint source control.
PMID- 28425289
TI - Imaging Metastable States and Transitions in Proteins by Trajectory Map.
AB - It has been a long-standing and intriguing issue to develop robust methods to
identify metastable states and interstate transitions from simulations or
experimental data to understand the functional conformational changes of
proteins. It is usually hard to define the complicated boundaries of the states
in the conformational space using most of the existing methods, and they often
lead to parameter-sensitive results. Here, we present a new approach, visualized
Trajectory Map (vTM), to identify the metastable states and the rare interstate
transitions, by considering both the conformational similarity and the temporal
successiveness of conformations. The vTM is able to give a nonambiguous
description of slow dynamics. The case study of a beta-hairpin peptide shows that
the vTM can reveal the states and transitions from all-atom MD trajectory data
even when a single observable (i.e, one-dimensional reaction coordinate) is used.
We also use the vTM to refine the folding/unfolding mechanism of HP35 in explicit
water by analyzing a 125 MUs all-atom MD trajectory and obtain folding/unfolding
rates of about 1/MUs, which are in good agreement with the experimental values.
PMID- 28425290
TI - Bandgap Narrowing of Lead-Free Perovskite-Type Hybrids for Visible-Light
Absorbing Ferroelectric Semiconductors.
AB - Perovskite-type hybrids (e.g., CH3NH3PbI3) hold great promise in photovoltaics
and optoelectronics due to their remarkable semiconducting properties and
potential ferroelectricity. However, to date, conclusive evidence for the bulk
ferroelectricity of CH3NH3PbI3 is still lacking. In this context, it is highly
desirable to assemble concrete perovskite ferroelectric hybrids with the
semiconducting feature. Here we report, for the first time, a class of lead-free
perovskite halides, (N-methylpyrrolidinium)3Sb2Cl9-9xBr9x (x = 0-1), showing
large ferroelectric polarizations (5.2-7.6 MUC/cm2) and pronounced semiconducting
performances. In particular, a wide tunability of their optical bandgaps (3.31
2.76 eV) enables superior visible-light-induced photocurrents (~10 nA/cm2), which
allow for assembling of the crystal-based photodetectors. Our work paves a new
way to build environmentally benign optoelectronic devices based on low-bandgap
ferroelectric hybrids.
PMID- 28425291
TI - Dispersed Vanadium in Three-Dimensional Dendritic Mesoporous Silica Nanospheres:
Active and Stable Catalysts for the Oxidative Dehydrogenation of Propane in the
Presence of CO2.
AB - The uniform monodispersed vanadium-doped three-dimensional dendritic mesoporous
silica nanospheres (nV-MSNSs) were successfully synthesized in a heterogeneous
oil-water biphase stratification reaction system and characterized by several
state-of-the-art methods. The synthesized nV-MSNSs were applied to the oxidative
dehydrogenation of the propane (ODHP) reaction with the presence of CO2 and
exhibited excellent catalytic performances. The results show that the vanadium
loading (1.3-8.0 wt %) evidently influences the textural properties, oxidation
state, and polymerization degree of vanadium species of nV-MSNSs. The specific
surface area (SBET), pore diameter (Dp), and pore volume (Vp) of nV-MSNSs
decrease with the loading of vanadium species. The excessively high vanadium
loading leads to the slight connection of nanospheres, but does not affect the
assembly and growth of the three-dimensional (3D) dendritic channels. The
percentage of highly dispersed vanadium VV species gradually increases and
attains the maximum value for 5.2V-MSNSs with the loading of vanadium and then
decreases with further vanadium addition. The higher-polymerized VOx species
gradually generates above 5.2 wt % vanadium content for nV-MSNSs. The lower
polymerized VOx species appear to be more active than the higher-polymerized VOx
species. Markedly, the 5.2V-MSNSs exhibit the highest catalytic activity with the
initial propane conversion of 58% for the ODHP. The excellent catalytic
performance can be maintained after eight reaction-regeneration cycles. The
silica mesoporous frameworks can be well preserved in the reaction-regeneration
cycles; meanwhile, the highly dispersed vanadium oxide also can be fully
recovered after in situ regeneration. Hence, nV-MSNS catalysts exhibit
outstanding activity and stability, and it would have a promising application in
the DH of alkanes.
PMID- 28425292
TI - Lactone Derivatives Produced by a Phaeoacremonium sp., an Endophytic Fungus from
Senna spectabilis.
AB - Three new isoaigialones, A, B, and C (1-3), along with aigialone (4), were
isolated from the crude EtOAc extract of a Phaeoacremonium sp., an endophytic
fungus obtained from the leaves of Senna spectabilis. The structures of these
compounds were elucidated based on the analysis of spectroscopic data. Compounds
2 and 4 were active against the phytopathogenic fungi Cladosporium
cladosporioides and C. sphaerospermum. This is the first report of metabolites
produced by an Phaeoacremonium sp., associated with S. spectabilis.
PMID- 28425293
TI - Cosensitized Porphyrin System for High-Performance Solar Cells with TOF-SIMS
Analysis.
AB - To date, development of organic sensitizers has been predominately focused on
light harvesting, highest occupied molecular orbital and lowest unoccupied
molecular orbital energy levels, and the electron transferring process. In
contrast, their adsorption mode as well as the dynamic loading behavior onto
nanoporous TiO2 is rarely considered. Herein, we have employed the time-of-flight
secondary ion mass spectrometry (TOF-SIMS) to gain insight into the competitive
dye adsorption mode and kinetics in the cosensitized porphyrin system. Using
novel porphyrin dye FW-1 and D-A-pi-A featured dye WS-5, the different bond
breaking mode in TOF-SIMS and dynamic dye-loading amount during the coadsorption
process are well-compared with two different anchoring groups, such as benzoic
acid and cyanoacrylic acid. With the bombardment mode in TOF-SIMS spectra, we
have speculated that the cyano group grafts onto nanoporous TiO2 as tridentate
binding for the common anchoring unit of cyanoacrylic acid and confirmed it
through extensive first-principles density functional theory calculation by
anchoring either the carboxyl or cyano group, which shows that the cyano group
can efficiently participate in the adsorption of the WS-5 molecule onto the TiO2
nanocrystal. The grafting reinforcement interaction between the cyano group and
TiO2 in WS-5 can well-explain the rapid adsorption characteristics. A strong
coordinate bond between the lone pair of electrons on the nitrogen or oxygen atom
and the Lewis acid sites of TiO2 can increase electron injection efficiencies
with respect to those from the bond between the benzoic acid group and the
Bronsted acid sites of the TiO2 surface. Upon optimization of the coadsorption
process with dye WS-5, the photoelectric conversion efficiency based on porphyrin
dye FW-1 is increased from 6.14 to 9.72%. The study on the adsorption dynamics of
organic sensitizers with TOF-SIMS analysis might provide a new venue for
improvement of cosensitized solar cells.
PMID- 28425294
TI - Reactivity of a Base-Stabilized Germanium(I) Dimer toward Group 9 Metal(I)
Chloride and Dimanganese Decacarbonyl.
AB - The reactivity of the 2-imino-5,6-methylenedioxylphenylgermanium(I) dimer toward
group 9 metal(I) chloride and dimanganese decacarbonyl is described. [LGe:]2 (1,
L = 2-imino-5,6-methylenedioxylphenyl) underwent a disproportionation reaction
with 1.5 equiv of group 9 metal(I) chloride [MCl(cod)]2 (M = Rh, Ir) in toluene
to afford a mixture of the group 9 metallogermylene-chlorometal(I) complexes
[LGeMU-{M(cod)}2Cl] (M = Rh (2), Ir (4)) and chlorogermylene-chlorometal(I)
complexes [L(Cl)GeM(cod)Cl] (M = Rh (3), Ir (5)), respectively. The
disproportionation property of 1 is further evidenced by its reaction with 0.5
equiv of Mn2(CO)10 in refluxing toluene to form a mixture of the manganogermylene
dimer [(LGe)MU-{Mn(CO)4}]2 (7) and free ligand [LH] (8). Compounds 2-5, 7, and 8
were elucidated by NMR spectroscopy, X-ray crystallography, and DFT calculations,
respectively.
PMID- 28425295
TI - Provider and Patient Determinants of Generic Levothyroxine Prescribing: An
Electronic Health Records-Based Study.
AB - BACKGROUND: Despite the availability of generic levothyroxine products for more
than a decade, uptake of these products is poor. OBJECTIVE: We sought to evaluate
determinants of generic prescribing of levothyroxine. METHODS: In a cross
sectional analysis of electronic health records data between 2010 and 2013, we
identified adult patients with a levothyroxine prescription from a primary-care
physician (PCP) or endocrinologist. We used mixed-effect logistic regression
models with random intercepts for prescribing provider to examine predictors of
generic levothyroxine prescribing. Models include patient, prescription, and
provider fixed-effect covariates. Odds ratios (ORs) and 95% CIs were generated.
Between-provider random variation was quantified by the intraclass correlation
coefficient (ICC). RESULTS: Study patients (n = 63 838) were clustered among 941
prescribing providers within 25 ambulatory care clinics. The overall prevalence
of generic prescribing of levothyroxine was 73%. In the multivariable mixed
effect model, patients were significantly less likely to receive generic
levothyroxine from an endocrinologist than a PCP (OR = 0.43; 95% CI = 0.33-0.55;
P < 0.001). Women were less likely to receive generic levothyroxine than men from
endocrinologists (OR = 0.68; 95% CI = 0.59-0.78; P < 0.001) but not from PCPs.
Between-provider variation in generic prescribing was 18.3% in the absence of
fixed-effect covariates and could be explained marginally by patient,
prescription, and provider factors (ICC = 15.9%). CONCLUSIONS: Generic
levothyroxine prescribing differed by PCPs and endocrinologists. Residual
variation in generic prescribing, after accounting for measurable factors,
indicates the need for provider interventions or patient education aimed at
improving levothyroxine generic uptake.
PMID- 28425296
TI - Medium- to long-term persistence with non-vitamin-K oral anticoagulants in
patients with atrial fibrillation: Australian experience.
AB - OBJECTIVE: Long-term anticoagulant therapy with non-valvular atrial fibrillation
(AF) is essential to prevent thromboembolic complications, especially ischemic
stroke. This study examines medium-term persistence in AF patients using a non
vitamin-K antagonist oral anticoagulant drug (NOAC). RESEARCH DESIGN AND METHODS:
We assessed national Pharmaceutical Benefit Scheme records December 2013 through
September 2016 for initial prescription of a NOAC in a 10% random sample of
concessional patients. Key outcome measures were: (a) proportions filling first
repeat prescription, (b) proportions persisting with NOAC over 12 and 30 months
and (c) proportions switching to another NOAC or warfarin. RESULTS: A total of
8656 patients with AF initiated a NOAC (3352 apixaban, 1340 dabigatran, 3964
rivaroxaban). Mean age was 77 years, 53% male; 91% collected the first repeat
prescription for any NOAC, 70% and 57% collected any NOAC or subsequent warfarin
prescription over 12 months and 30 months respectively; 8.9% had switched to
warfarin. The proportions switching from apixaban, dabigatran and rivaroxaban to
a different NOAC were 14%, 31% and 17% respectively. In a regression model
adjusting for age, gender and comorbidity, apixaban-initiated patients over 30
months were 28% more likely to persist with any anticoagulant therapy compared
with dabigatran-initiated patients (hazard ratio [95% CI] 1.28 [1.16-1.42]) and
15% more likely to persist compared with rivaroxaban-initiated (1.15 [1.06
1.24]). Rivaroxaban-initiated patients were 12% more likely to persist compared
with dabigatran-initiated patients (1.12 [1.02-1.24]). CONCLUSIONS: Long-term
persistence with anticoagulation in patients with AF remains a concern, even with
NOACs. Patients initiated to apixaban appear to experience better medium-term
persistence compared with rivaroxaban or dabigatran.
PMID- 28425297
TI - New approaches for itaconic acid production: bottlenecks and possible remedies.
AB - Currently, growing attention is being devoted to the conversion of biomass into
value-added products, such as itaconic acid (IA), which is considered as the
cleanest alternative to petroleum-based acrylic acid. IA is an unsaturated
dicarboxylic acid that is used as a building block chemical for the production of
several value-added products such as poly-itaconic acid. IA and its derivatives
have a wide range of potential applications in textile, paint, pharmaceutical and
chemical industries. Presently, industries are producing IA on the large scale by
fermentation from glucose. However, due to the primary utility of glucose as a
food, it cannot meet the global demand for IA production in an economical way.
The main challenge, so far, has been the production technology, which does not
support cost-effective and competitive production of IA. This review discusses
the various bottlenecks faced during each step of IA production, along with
possible remedies to deal with these problems. Furthermore, it reviews the recent
progress in fermentative IA production and sheds light on different
microorganisms used, potential substrates and fermentation conditions. The review
also covers market potential for IA, which indicates that IA can be produced cost
effectively from sustainable substrates, and it has the potential to replace
petrochemicals in the near future.
PMID- 28425298
TI - Understanding self-reported difficulties in decision-making by people with autism
spectrum disorders.
AB - Autobiographical accounts and a limited research literature suggest that adults
with autism spectrum disorders can experience difficulties with decision-making.
We examined whether some of the difficulties they describe correspond to
quantifiable differences in decision-making when compared to adults in the
general population. The participants (38 intellectually able adults with autism
spectrum disorders and 40 neurotypical adults) were assessed on three tasks of
decision-making (Iowa Gambling Task, Cambridge Gamble Task and Information
Sampling Task), which quantified, respectively, decision-making performance and
relative attention to negative and positive outcomes, speed and flexibility, and
information sampling. As a caution, all analyses were repeated with a subset of
participants ( nASD = 29 and nneurotypical = 39) who were not taking
antidepressant or anxiolytic medication. Compared to the neurotypical
participants, participants with autism spectrum disorders demonstrated slower
decision-making on the Cambridge Gamble Task, and superior performance on the
Iowa Gambling Task. When those taking the medications were excluded, participants
with autism spectrum disorders also sampled more information. There were no other
differences between the groups. These processing tendencies may contribute to the
difficulties self-reported in some contexts; however, the results also highlight
strengths in autism spectrum disorders, such as a more logical approach to, and
care in, decision-making. The findings lead to recommendations for how adults
with autism spectrum disorders may be better supported with decision-making.
PMID- 28425299
TI - Posture of Patients with Sleep Apnea During Sleep.
AB - The relationship between sleep apnea syndrome (SAS) and posture during sleep has
been noted and the beneficial effect of an optimal posture on sleep apnea has
been empirically indicated. We investigated this effect in a group of subjects
that included obese patients and found that the apnea-hypopnea index (AHI) may be
normalized in the lateral position, even among patients severely affected with
apnea. Among those with intermediate or lower AHI values, sleeping in a lateral
position markedly improved the symptoms, with AHI even approaching the normal
range in many patients. A tendency was noted for AHI to rise regardless of
posture but in proportion to the increase in body mass index (BMI). In other
words, the improvement due to changes in posture became increasingly
insignificant with increase in BMI.
PMID- 28425300
TI - State of the Art.
PMID- 28425301
TI - Development of a novel rationally designed antibiotic to inhibit a nontraditional
bacterial target.
AB - The search for new nontraditional targets is a high priority in antibiotic design
today. Bacterial membrane energetics based on sodium ion circulation offers
potential alternative targets. The present work identifies the Na+-translocating
NADH:ubiquinone oxidoreductase (Na+-NQR), a key respiratory enzyme in many
microbial pathogens, as indispensible for the Chlamydia trachomatis infectious
process. Infection by Chlamydia trachomatis significantly increased first H+ and
then Na+ levels within the host mammalian cell. A newly designed furanone Na+-NQR
inhibitor, PEG-2S, blocked the changes in both H+ and Na+ levels induced by
Chlamydia trachomatis infection. It also inhibited intracellular proliferation of
Chlamydia trachomatis with a half-minimal inhibitory concentration in the
submicromolar range but did not affect the viability of mammalian cells or
bacterial species representing benign intestinal microflora. At low nanomolar
concentrations (IC50 value = 1.76 nmol/L), PEG-2S inhibited the Na+-NQR activity
in sub-bacterial membrane vesicles isolated from Vibrio cholerae. Taken together,
these results show, for the first time, that Na+-NQR is critical for the
bacterial infectious process and is susceptible to a precisely targeted
bactericidal compound in situ. The obtained data have immediate relevance for
many different diseases caused by pathogenic bacteria that rely on Na+-NQR
activity for growth, including sexually transmitted, pulmonary, oral, gum, and
ocular infections.
PMID- 28425302
TI - Probing morphological, syntactic and pragmatic knowledge through answers to wh
questions in children with SLI.
AB - PURPOSE: This study investigated aspects of morphology, syntax and pragmatics in
children with Specific Language Impairment (SLI). These areas of language were
investigated by evaluating children's answers to wh-questions. METHOD: Elicited
production methodology was used to evoke answers to three types of wh-questions.
There were 54 participants: 18 children with SLI (mean age = 5;3); 18 language
matched children matched on mean length of utterance (mean age = 3;4) and 18 age
matched children (mean age = 5;3). RESULT: The SLI group demonstrated
comprehension of the wh-questions, as revealed by their answers using the
appropriate syntactic category. Children with SLI also demonstrated knowledge of
pragmatics by using a pronoun to refer to a discourse referent that was
previously introduced as a full noun phrase. Unlike the control children,
children with SLI did not show sensitivity to one measure of the Maxim of
Quantity; they gave more full sentence answers to wh-questions in contexts when
most speakers would give a shorter, fragment answer. The tense-related morphology
was also frequently omitted from children's answers. CONCLUSION: The experiment
revealed that children with SLI did well on syntactic and pragmatic measures. The
greatest challenge was in providing tense-related morphemes in their answers to
questions.
PMID- 28425303
TI - A Retrospective Study Assessing Safety and Efficacy of Bipolar Radiofrequency
Ablation for Knee Chondral Lesions.
AB - OBJECTIVE: Bipolar radiofrequency (bRF) ablation is gaining popularity as a
treatment modality for unstable knee chondral lesions of the knee. Limited
reports of osteonecrosis and chondrolysis have been published; however, there is
little data examining the safety of this treatment in larger series. This study
aims to evaluate the safety and efficacy of bRF in the treatment of chondral
lesions encountered during knee arthroscopy. DESIGN: A retrospective evaluation
of adverse outcomes in patients that underwent treatment of chondral lesions
using bRF was undertaken. Secondary outcome measures included change in patient
reported outcome scores and its correlation to patient demographics and quality
of chondral and meniscal lesions using Chondropenia Severity Score. RESULTS: Only
2.2% and 2.7% of the patients had a postoperative complication or required a
reoperation, respectively. None of the complications were directly related to the
use of bRF. A statistically significant difference was observed when comparing
pre- and postoperative scores in all normalized categories ( P < 0.0001). No
statistically significant correlation was found between change in self-reported
scores and Chondropenia Severity Score. CONCLUSION: Bipolar radiofrequency
ablation is a safe modality in treatment of chondral lesions.
PMID- 28425304
TI - Preparation and evaluation of 1-deoxynojirimycin sustained-release pellets vs
conventional immediate-release tablets.
AB - 1-Deoxynojirimycin sustained-release pellets, which exhibit known release and
absorption profiles, are used for the treatment of diabetes mellitus. In this
study, a fluidised bed coater was employed to prepare new, drug-loaded pellets.
In the dissolution test, it was found that 1-DNJ pellets exhibited a sustained
release effect after being coated with hydroxypropyl methyl cellulose phthalate
55 S. For sustained-release pellets and immediate-release pellets, there was
significant difference in the mean cumulative drug concentration profile in
different media evaluation. In the bioavailability study, the ratio of mean
relative bioavailability of the SR pellets to the IR tablets was calculated by
the DAS from the AUC0-24 h of 1-DNJ and was found to be 117.3%. This suggested
that the behaviour in vivo of the 1-DNJ SR pellets was superior to the IR
tablets, which indicated the designed preparation method of the 1-DNJ SR pellets
was acceptable for achieving sustained release of 1-DNJ with enhanced
bioavailability.
PMID- 28425305
TI - Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.
AB - OBJECTIVE: The aim of this work was to develop an amorphous solid
dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a
novel polymer Soluplus(r) (BASF, Germany) using a freeze-drying technique, in
order to improve dissolution and absorption through the nasal route.
SIGNIFICANCE: The small volume of fluid present in the nasal cavity limits the
absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically
insoluble and normally administered as a suspension-based nasal spray. METHODS:
The formulation was prepared through freeze-drying of polymer-drug solution. The
formulation was assessed for its physicochemical (specific surface area,
calorimetric analysis and X-ray powder diffraction), release properties and
aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells,
in order to elucidate the efficacy of the Soluplus-BUD formulation. RESULTS: The
freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a
specific surface area of 1.4334 +/- 0.0178 m2/g. The calorimetric analysis
confirmed an interaction between BUD and Soluplus and X-ray powder diffraction
the amorphous status of the drug. The freeze-dried formulation (LYO) showed
faster release compared to both water-based suspension and dry powder commercial
products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca),
showed suitable aerodynamic characteristics for nasal drug delivery. The
permeation across RPMI 2650 nasal cell model was higher compared to a commercial
water-based BUD suspension. CONCLUSIONS: Soluplus has been shown to be a
promising polymer for the formulation of BUD amorphous solid suspension/solution.
This opens up opportunities to develop new formulations of poorly soluble drug
for nasal delivery.
PMID- 28425306
TI - Therapeutic targeting and patient selection for cancers with homologous
recombination defects.
AB - INTRODUCTION: DNA double-strand breaks (DSBs) are toxic DNA lesions that can be
repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR).
Mutations in HR genes elicit a predisposition to cancer; yet, they also result in
increased sensitivity to certain DNA damaging agents and poly (ADP-ribose)
polymerase (PARP) inhibitors. To optimally implement PARP inhibitor treatment, it
is important that patients with HR-deficient tumors are adequately selected.
Areas covered: Herein, the authors describe the HR pathway mechanistically and
review the treatment of HR-deficient cancers, with a specific focus on PARP
inhibition for BRCA1/2-mutated breast and ovarian cancer. In addition, mechanisms
of acquired PARP inhibitor resistance are discussed. Furthermore, combination
therapies with PARP inhibitors are reviewed, in the context of both HR-deficient
and HR-proficient tumors and methods for proper patient selection are also
discussed. Expert opinion: Currently, only patients with germline or somatic
BRCA1/2 mutations are eligible for PARP inhibitor treatment and only a proportion
of patients respond. Patients with HR-deficient tumors caused by other
(epi)genetic events may also benefit from PARP inhibitor treatment. Ideally,
selection of eligible patients for PARP inhibitor treatment include a functional
HR read-out, in which cancer cells are interrogated for their ability to perform
HR repair and maintain replication fork stability.
PMID- 28425307
TI - Epidural fentanyl does not affect cervical dilation and progress of first stage
of vaginal delivery: a randomized, double-blind study.
AB - OBJECTIVE: Local anesthetics combined with opioids are commonly used in labor
epidural analgesic schemes. This study investigated if the addition of fentanyl
to epidural ropivacaine can affect cervical dilation and progress of vaginal
delivery. METHODS: Sixty-two nulliparous parturients were randomized to receive
epidurally 8 ml ropivacaine 0.2% combined with fentanyl 20 MUg (F/R-group, n =
31) or with normal saline 0.4 ml (R-group, n = 31), every hour. Rescue doses of 5
ml ropivacaine 0.2% were also administered. Measurements were performed every 60
min until full cervical dilation. The primary end-point was the time to reach 10
cm cervical dilation. Secondary outcomes were Bishop scores, mode of delivery,
total ropivacaine dose, pain, and satisfaction scores (numerical scale, 0-10).
RESULTS: Data from 60 parturients (29 in the F/R and 31 in the R-group) were
analyzed. The F/R-group had 26 vaginal deliveries (four instrumentally assisted),
and three cesarean deliveries. The R-group had 27 vaginal deliveries (six
instrumentally assisted) and 4 cesarean deliveries. Time to 10-cm cervical
dilation did not differ between the groups (4 +/- 2.4 h in the F/R-group vs 4.4
+/- 2.1 h in the R-group, p = .341). The number of women remaining in the study
every hour until full cervical dilation and Bishop scores for a 4-h period did
not differ between the groups (p = .617). Total ropivacaine dose was comparable
between the groups, but the F/R-group reported significantly lower pain (p = .01)
and higher satisfaction scores (p = .001). CONCLUSIONS: The addition of fentanyl
to ropivacaine 0.2% solution did not affect cervical dilation and progress of the
first stage of labor, but improved both analgesia and satisfaction.
PMID- 28425308
TI - The effect of molecular weights of microencapsulating polymers on viability of
mouse-cloned pancreatic beta-cells: biomaterials, osmotic forces and potential
applications in diabetes treatment.
AB - INTRODUCTION: Ideal cell-containing microcapsules should be capable of
maintaining cell viability and exhibit significant structural stability to
support cellular functionality. To date, such microcapsules remain unavailable;
thus, this study used our well-established microencapsulating methods to examine
a total of 32 different microencapsulating formulations and correlate polymers'
molecular weights (Mwt) and UDCA addition, with cell viability and microcapsules'
stability, postmicroencapsulation. METHODS: MIN6 mouse-cloned pancreatic beta
cells were microencapsulated using control (n = 16; without UDCA) and test (n =
16; with UDCA) different polymers. Confocal microscopic imaging, cell viability,
and microcapsules' stability were assessed. RESULTS: Best cell viability (>50%)
was obtained at average Mwt of 50,000 g/mol (poly-l-ornithine), followed by
110,000 g/mol (poly-l-lysine). There was no linear correlation between Mwt and
viability. Confocal imagining showed similar microcapsules' shape and cell
distribution among all different polymers' molecular weights, which suggests that
the microencapsulating method was efficient and maintained microcapsules'
uniformity. UDCA addition resulted in enhanced osmotic stability of the
microcapsules and improved cell viability, when the formulation contained 1%
polylornithine, 1% polyethylene glycol, 20% Eudragit(r) NM30D, 1%
polytetrafluoroethylene, or 5% pentamethylcyclopentasiloxane. CONCLUSIONS: UDCA
addition improved microenvironmental conditions within the microcapsules but this
effect was largely dependent on the polymer systems used.
PMID- 28425309
TI - Laboratory tests on heat treatment of ballast water using engine waste heat.
AB - Waste heat recovery from shipboard machineries could be a potential source for
heat treatment of ballast water. Similar to a shipboard schematic arrangement, a
laboratory-scale engine-heat exchanger set-up harvesting waste heat from jacket
water and exhaust gases was erected to test the level of species' mortalities.
Mortalities were also assessed under experimental conditions for cultured and
natural plankton communities at laboratory level. Effect of pump impellers on
species' mortalities were also tested. Exposures between 60 degrees C and 70
degrees C for 60 sec resulted in 80-100% mortalities. Mortalities due to pump
impeller effects were observed in the range of 70-100% for zooplankton. On the
laboratory-scale arrangement, >95% mortalities of phytoplankton, zooplankton and
bacteria were recorded. It was demonstrated that the temperature of tropical sea
waters used as secondary coolant can be raised to cause species' mortalities,
employing engine exhaust gases. The results also indicated that pump impeller
effects will enhance species' mortalities. The limitations of the shipboard
application of this method would be the large ballast volumes, flow rates and
time for treatment.
PMID- 28425310
TI - Comments on prediction of the aqueous solubility using the general solubility
equation (GSE) versus a genetic algorithm and a support vector machine model.
AB - The general solubility equation (GSE) is the state-of-the-art method for
estimating the aqueous solubilities of organic compounds. It is an extremely
simple equation that expresses aqueous solubility as a function of only two
inputs: the octanol-water partition coefficient calculated by readily available
softwares like clogP and ACD/logP, and the commonly known melting point of the
solute. Recently, Bahadori et al. proposed that their genetic algorithm support
vector machine is a "better" predictor. This paper compares the use of the of
Bahadori et al. model for the prediction of aqueous solubility to the existing
GSE model.
PMID- 28425311
TI - Later adults' cultural life scripts of middle and later adulthood.
AB - The cultural life script (CLS) refers to expected prototypical life events, often
including life transitions overwhelmingly occurring at ages 11-30. This study
outlined CLS events at ages after the majority of these events typically occur.
Participants, age 38-76, nominated events they expected a person of their age to
experience in the future. Participants rated each event's valence, importance,
prevalence, and expected age of occurrence. Events were coded into three
categories: the normative CLS for events listed by previous CLS studies,
offspring's CLS for experiencing CLS events of offspring, and later adulthood CLS
for other events nominated by at least 4% of participants. Results suggest
scripted events highlighting positivity and change. Offspring's CLS was more
positive and occurred earlier than others. Correlations emerged between event
characteristics and well-being. Results affirm the prominence of transitions in
memory, and suggest ways that older adults maintain well-being despite a cultural
narrative that emphasizes decline.
PMID- 28425312
TI - Activation of spinal alpha-7 nicotinic acetylcholine receptor shortens the
duration of remifentanil-induced postoperative hyperalgesia by upregulating KCC2
in the spinal dorsal horn in rats.
AB - Background Accumulating evidence has shown that the signal from spinal brain
derived neurotrophic factor/tyrosine receptor kinase B-K+-Cl- cotransporter-2
plays a critical role in the process of pain hypersensitivity. The activation of
alpha-7 nicotinic acetylcholine receptors could have an analgesic effect on
remifentanil-induced postoperative hyperalgesia. Nevertheless, whether
intrathecal administration of PNU-120596, an alpha-7 nicotinic acetylcholine
receptors selective type II positive allosteric modulator, before surgery could
affect the duration of remifentanil-induced postoperative hyperalgesia remains
unknown, and the effects of alpha-7 nicotinic acetylcholine receptors activation
on the brain-derived neurotrophic factor/tyrosine receptor kinase B-K+-Cl-
cotransporter-2 signal in the spinal dorsal horn of rats with remifentanil
induced postoperative hyperalgesia is still enigmatic. Results We demonstrated
that the brain-derived neurotrophic factor/tyrosine receptor kinase B-K+-Cl-
cotransporter-2 signal played a critical role in the development of remifentanil
induced postoperative hyperalgesia. Intrathecal administration of PNU-120596 (8
ug/kg, 15 min before surgery) was associated with earlier signs of recovery from
remifentanil-induced postoperative hyperalgesia. Simultaneously, remifentanil
induced postoperative hyperalgesia-induced K+-Cl- cotransporter-2 downregulation
was partly reversed and coincided with a decreased expression of brain-derived
neurotrophic factor/tyrosine receptor kinase B in the spinal dorsal horn,
approximately correlating with the time course of the nociceptive behavior.
Moreover, intrathecal administration of the K+-Cl- cotransporter-2 inhibitor
VU0240551 significantly reduced the analgesic effect of PNU-120596 on
remifentanil-induced postoperative hyperalgesia. Conclusions The activation of
alpha-7 nicotinic acetylcholine receptors induced a shorter duration of
remifentanil-induced postoperative hyperalgesia by restoring the brain-derived
neurotrophic factor/tyrosine receptor kinase B-K+-Cl- cotransporter-2 signal in
the spinal dorsal horn of rats, which provides new insight into treatment in
clinical postoperative pain management.
PMID- 28425313
TI - Moral Distress Among School Nurses.
AB - School nurses are well positioned to provide care to a diverse population of
school-age children, but their role and work environment can present a variety of
moral dilemmas leading to moral distress. The purpose of this study is to
identify the moral distress level that exists in school nurses and to describe
its relationship to common moral dilemmas and school nurse characteristics. Data
were collected through face-to-face attendance at school nurse meetings in North
Carolina where 307 school nurses participated in the survey. Moral distress was
measured using the moral distress thermometer, and common moral dilemmas were
identified using a researcher developed questionnaire. Almost all of the school
nurses (97.3%) experienced some degree of moral distress. Each of the common
moral dilemmas was positively correlated with moral distress levels. The findings
suggest that many of the common moral dilemmas experienced by school nurses are
strongly related to moral distress.
PMID- 28425314
TI - Effect of transmucosal corn syrup application on postoperative blood glucose
concentrations in kittens.
AB - Objectives The aim of the study was to determine the effect of a common clinical
practice, the transmucosal (TM) application of corn syrup, on postoperative blood
glucose concentrations in kittens. Methods This study was designed as a
randomized controlled trial. Seventy-five kittens between the age of 8 and 16
weeks scheduled for surgical sterilization by gonadectomy at an animal shelter
were enrolled. Kittens were randomly assigned to either a routine treatment group
that received the shelter's typical postoperative application of corn syrup
immediately following gonadectomy or to a control group that did not receive
typical treatment. Three blood glucose measurements were obtained per kitten:
baseline reading prior to preoperative examination, immediately postoperatively
and 20 mins postoperatively. The median values of the 20 min postoperative blood
glucose reading for the control and treatment groups were compared using the
Wilcoxon rank-sum test. Results Postoperative application of corn syrup to the
oral mucosa of kittens did not result in significant elevations in blood glucose
compared with controls. No kitten was hypoglycemic (?60 mg/dl) at any point
during the study. Conclusions and relevance TM application of corn syrup did not
affect postoperative blood glucose concentrations in kittens. Protocols that use
routine TM administration of corn syrup in kittens should be re-evaluated.
PMID- 28425315
TI - Caring in nursing homes to promote autonomy and participation.
AB - BACKGROUND: Autonomy and participation are threatened within the group of older
people living in nursing homes. Evidence suggests that healthcare personnel act
on behalf of older people but are still excluding them from decision-making in
everyday care. OBJECTIVE: The purpose was to describe registered nurses'
experience of caring for older people in nursing homes to promote autonomy and
participation. RESEARCH DESIGN: A descriptive design with a phenomenological
approach was used. Data were collected by semi-structured individual interviews.
Analysis was inspired by Giorgi's method. Participants and research context: A
total of 13 registered nurses from 10 nursing homes participated. Ethical
considerations: Ethical approval was obtained from the Regional Research Ethics
Committee. Informed consent was achieved and confidentiality guaranteed.
FINDINGS: The essence of caring for older people in nursing homes to promote
autonomy and participation consisted of registered nurses' awareness of older
people's frailty and the impact of illness to support health and well-being, and
awareness of acknowledgement in everyday life and trusting relationships. Paying
attention to older people by being open to the persons' wishes were aspects that
relied on registered nurses' trusting relationships with older people, their
relatives and surrounding healthcare personnel. The awareness reflected
challenges in caring to promote older people's right to autonomy and
participation in nursing homes. Registered nurses' strategies, hopes for and/or
concerns about development of everyday life in nursing homes were revealed and
mirrored their engagement in caring for older people. DISCUSSION AND CONCLUSION:
Awareness of older people's frailty in nursing homes and the importance of
maintained health and well-being were described as the main source for promoting
autonomy and participation. Everyday life and care in nursing homes needs to be
addressed from both older people's and healthcare personnel's perspectives, to
promote autonomy and participation for residents in nursing homes.
PMID- 28425316
TI - Carbon-covered mesoporous silica and its application in Rhodamine B adsorption.
AB - Modified versions of MCM-41 and SBA-15 were obtained from sucrose by carbon
deposition. The ability of the resulting materials, MCM-41 CC and SBA-15 CC, to
remove Rhodamine B from aqueous solutions was evaluated. TG/DTG, XRD, Nitrogen
Adsorption (BET), and SEM were used to characterize the materials. Adsorption was
investigated by finite bath studies. To characterize the adsorption behavior and
mechanism, kinetics and equilibrium were assessed. MCM-41 CC provided the best
adsorption results: adsorptive capacity of 11.91 mg of dye/g of material and
91.95% w/v dye removal (C0 = 50 mg L-1). The sucrose particles interacted well,
to result in improved area and micropore volume. Hence, carbon deposition can
afford materials with increased adsorptive capacity depending on the sieve
employed during their preparation.
PMID- 28425317
TI - Mortality risk factors from converting off-pump coronary artery bypass to on-pump
coronary artery bypass.
AB - INTRODUCTION: A number of large-scale retrospective studies revealed that off
pump coronary artery bypass (OPCAB) was superior to on-pump coronary artery
bypass (ONCAB). The aim of the study was to investigate risk factors for
mortality when OPCAB is converted to ONCAB. METHODS: Patients who underwent OPCAB
conversion to ONCAB at the Beijing Anzhen Hospital between January 2003 and
January 2013 were assigned to the non-survivor and survivor groups. Background
demographics, illness history and preoperative, intraoperative and postoperative
variables were compared. RESULTS: Of the 247 cases, 15.4% of the patients died.
Patients in the non-survivor group were older and more frequently had diabetes
mellitus (DM), arrhythmia, myocardial infarction (MI) in the past 30 days (all
p<0.05) and MI combined with mitral regurgitation (p<0.0001); they more
frequently had bigger left ventricular end-diastolic dimension (p=0.0019),
greater fall in blood pressure, ventricular fibrillation for longer periods,
longer conversion time and bypass graft occlusion. All patients in the non
survivor group received intra-aortic balloon pump compared to 89.5% in the
survivor group and extracorporeal membrane oxygenation was more common. Left main
coronary artery disease (OR=4.431, 95%CI: 2.440-8.048, p<0.0001), blood pressure
decline ?40 mmHg (OR=0.509, 95%CI: 0.447-0.580, p<0.0001) and time for conversion
to ONCAB ?20 min were independently associated with mortality. Rates of
postoperative complications, such as renal failure, cerebral infarction or
hemorrhage, MI and redo sternotomy, were higher in the non-survivor group.
CONCLUSIONS: Conversion from OPCAB to ONCAB is associated with high mortality.
Risk factors include left main artery disease and duration of blood pressure
decline >40 min.
PMID- 28425318
TI - Exploring families' experiences of health: contributions to a model of family
health.
AB - Child health and developmental outcomes are influenced by the health of the
family and the context created. Research suggests symptoms of poor family health
(e.g. suboptimal family interactions, parenting stress) yet there is limited
understanding of the factors which contribute to robust family health which may
unveil opportunities for targeted intervention and family health promotion. The
present study examined families' experiences of family health and factors
contributing to family health. We performed a qualitative study using
constructivist grounded theory methods to guide our understanding of family
health for families with typically developing children aged 5-18. Interviews were
conducted in family homes and all members were invited to participate. Data from
interviews were transcribed, coded, thematically analyzed, and verified with
select families. Ten families, including 10 mothers, 8 fathers, and 15 children
participated in the study. Participants described family health as a process of
balance, living purposefully, and sharing experiences together in alignment with
family identity. Mediating family health were processes of awareness and
reflection, and adapting, adjusting, and changing in response to family life
including external stress factors. Results highlight the possibility for
healthcare practitioners to facilitate families' self-reflection and awareness
about their health in order to mediate family health development.
PMID- 28425319
TI - Abandoned Luncheonettes: Can Health Promotion Stem the Loss of Social Capital?
PMID- 28425320
TI - The Art of Health Promotion.
PMID- 28425322
TI - Determinants of Health-Related Quality of Life Among Elderly: Evidence From Chi
Linh Town, Vietnam.
AB - As Vietnam confronts with the challenge of an aging population, the importance of
quality of life for elderly people becomes apparent. This article aims to assess
health-related quality of life (HRQoL) and its correlates for the elderly, using
a cross-sectional study design. A total of 1599 adults, aged 60 years and older,
were drawn from the 2016 baseline survey of Chi Linh Health and Demographic
Surveillance System (CHILILAB HDSS), which incorporated the EQ-5D, to measure
HRQoL. Data were analyzed using multivariate linear regression analyses. The EQ
5D index of the elderly was found to be 0.871 (95% confidence interval = 0.862
0.880). After controlling for covariates, there were statistically significant
associations between lower HRQoL and older age (>=80 years), lower education, no
pension, chronic disease(s), and health insurance schemes targeting poor/near
poor/priority groups. Current and future policies for improving HRQoL in old age
should be extended to cover the most vulnerable groups.
PMID- 28425323
TI - Enhanced solubility of piperine using hydrophilic carrier-based potent solid
dispersion systems.
AB - CONTEXT: Piperine alkaloid, an important constituent of black pepper, exhibits
numerous therapeutic properties, whereas its usage as a drug is limited due to
its poor solubility in aqueous medium, which leads to poor bioavailability.
OBJECTIVE: Herein, a new method has been developed to improve the solubility of
this drug based on the development of solid dispersions with improved dissolution
rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG)
and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of
piperine and carriers were also prepared for comparison. METHODS: The
physicochemical properties of the prepared solid dispersions were examined using
SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid
dispersions was recorded and compared with that of the pure piperine and physical
mixtures. The effect of these carriers on the aqueous solubility of piperine has
been investigated. RESULTS: The solid dispersions of piperine with Sor, PEG and
PVP exhibited superior performance for the dissolution of piperine with a drug
release of 70%, 76% and 89%, respectively after 2 h compared to physical mixtures
and pure piperine, which could be due to its transformation from crystalline to
amorphous form as well as the attachment of hydrophilic carriers to the surface
of poorly water-soluble piperine. CONCLUSION: Results suggest that the piperine
solid dispersions prepared with improved in vitro release exhibit potential
advantage in delivering poorly water-soluble piperine as an oral supplement.
PMID- 28425324
TI - Persistent idiopathic facial pain.
AB - Background Persistent idiopathic facial pain (PIFP) is a chronic disorder
recurring daily for more than two hours per day over more than three months, in
the absence of clinical neurological deficit. PIFP is the current terminology for
Atypical Facial Pain and is characterized by daily or near daily pain that is
initially confined but may subsequently spread. Pain cannot be attributed to any
pathological process, although traumatic neuropathic mechanisms are suspected.
When present intraorally, PIFP has been termed 'Atypical Odontalgia', and this
entity is discussed in a separate article in this special issue. PIFP is often a
difficult but important differential diagnosis among chronic facial pain
syndromes. Aim To summarize current knowledge on diagnostic criteria,
differential diagnosis, pathophysiology and management of PIFP. Methods We
present a narrative review reporting current literature and personal experience.
Additionally, we discuss and differentiate the common differential diagnoses
associated with PIFP including traumatic trigeminal neuropathies, regional
myofascial pain, atypical neurovascular pains and atypical trigeminal neuropathic
pains. Results and conclusion The underlying pathophysiology in PIFP is still
enigmatic, however neuropathic mechanisms may be relevant. PIFP needs
interdisciplinary collaboration to rule out and manage secondary causes,
psychiatric comorbidities and other facial pain syndromes, particularly
trigeminal neuralgia. Burden of disease and psychiatric comorbidity screening is
recommended at an early stage of disease, and should be addressed in the
management plan. Future research is needed to establish clear diagnostic criteria
and treatment strategies based on clinical findings and individual
pathophysiology.
PMID- 28425325
TI - Macro- and microstructural alterations of the subcortical structures in episodic
cluster headache.
AB - Background Previous functional and structural imaging studies have revealed that
subcortical structures play a key a role in pain processing. The recurring
painful episodes might trigger maladaptive plasticity or alternatively
degenerative processes that might be detected by MRI as changes in size or
microstructure. In the current investigation, we aimed to identify the macro- and
microstructural alterations of the subcortical structures in episodic cluster
headache. Methods High-resolution T1-weighted and diffusion-weighted MRI images
with 60 gradient directions were acquired from 22 patients with cluster headache
and 94 healthy controls. Surface-based segmentation analysis was used to measure
the volume of the subcortical nuclei, and mean diffusion parameters (fractional
anisotropy, mean, radial and axial diffusivity) were determined for these
structures. In order to understand whether the size and diffusion parameters
could be investigated in a headache lateralised manner, first the asymmetry of
the size and diffusion parameters of the subcortical structures was analysed.
Volumes and diffusion parameters were compared between groups and correlated with
the cumulative number of headache days. To account for the different size of the
patient and control group, a bootstrap approach was used to investigate the
stability of the findings. Results A significant lateralisation of the size
(caudate, putamen and thalamus) and the diffusion parameters of the subcortical
structures were found in normal controls. In cluster headache patients, the mean
fractional anisotropy of the right amygdalae, the mean axial and mean diffusivity
of the right caudate nucleus and the radial diffusivity of the right pallidum
were higher. The mean anisotropy of the right pallidum was lower in patients.
Conclusion The analysis of the pathology in the subcortical structures in
episodic cluster headache reveals important features of the disease, which might
allow a deeper insight into the pathomechanism of the pain processing in this
headache condition.
PMID- 28425326
TI - Validity, reliability and sensitivity of the NORLA-6: Naming and oral reading for
language in aphasia 6-point scale.
AB - PURPOSE: Evaluation of the Naming and Oral Reading for Language in Aphasia 6
point scale (NORLA-6), a scoring system of oral reading and naming performance in
aphasia. METHOD: Data were drawn from 91 participants with non-fluent aphasia
secondary to left-hemisphere stroke across four treatment studies. To assess
validity, Spearman's correlations were calculated between the NORLA-6 and the
Gray Oral Reading Test-Fourth Edition (GORT-4) Accuracy score, GORT-4 Rate score
and the Boston Naming Test (BNT). Inter-rater and test-retest reliability were
evaluated using correlations. Sensitivity to change following oral reading
intervention was analysed using Wilcoxon Signed Rank tests between pre- and post
treatment NORLA-6 scores. RESULT: NORLA-6 performance was significantly
correlated (p < 0.001) with all reference tests (GORT-4 Accuracy, rs=0.84; GORT-4
Rate, rs= 0.61; and BNT, rs= 0.92). Inter-rater (ICC >=0.90) and test-retest (r >
0.92) reliability were both excellent. Sensitivity following oral reading
intervention was demonstrated in both oral reading accuracy and rate (p < 0.004).
CONCLUSION: The NORLA-6 is a valid and reliable measure of oral reading and
naming performance. It also demonstrates sensitivity to change in treatment
targeted behaviours. Therefore, the NORLA-6 scale may enhance outcome measurement
in both clinical practice and aphasia research.
PMID- 28425327
TI - Cross-sectional quantitative RT-PCR study of feline coronavirus viremia and
replication in peripheral blood of healthy shelter cats in Southern California.
AB - Objectives The objectives of this study were to determine the prevalence of
feline coronavirus (FCoV) viremia, and its replication in peripheral blood using
quantitative RT-PCR (qRT-PCR) methodology in a population of 205 healthy shelter
cats in Southern California, as well as to assess any possible connection to
longitudinal development of feline infectious peritonitis (FIP). Methods The
study was performed on buffy-coat samples from EDTA-anticoagulated whole blood
samples of 205 healthy shelter cats. From 50 of these cats, fecal samples were
also examined. FCoV genomic and subgenomic RNA in the buffy coats was amplified
by a total FCoV RNA qRT-PCR. Evidence for FCoV replication in peripheral blood
and feces was obtained by M gene mRNA qRT-PCR. Results Nine of 205 cats (4.4%)
were viremic by the total FCoV RNA qRT-PCR, and one of these cats had evidence of
peripheral FCoV blood replication by an FCoV mRNA qRT-PCR. The single cat with
peripheral blood replication had a unique partial M gene sequence distinct from
positive controls and previously published FCoV sequences. Neither seven of the
nine viremic cats with follow-up nor the single cat with replicating FCoV with
positive qRT-PCR results developed signs compatible with FIP within 6 months of
sample collection. Conclusions and relevance FCoV viremia and peripheral blood
replication in healthy shelter cats have a low prevalence and do not correlate
with later development of FIP in this study population, but larger case-control
studies evaluating the prognostic accuracy of the qRT-PCR assays are needed.
PMID- 28425328
TI - The use of a smartwatch as a prompting device for people with acquired brain
injury: a single case experimental design study.
AB - Prompting-based memory compensation is a potential application for smartwatches.
This study investigated the usability and efficacy of a Moto360 smartwatch as a
memory aid. Four community dwelling adults with memory difficulties following
acquired brain injury (ABI) were included in an A-B-A single case experimental
design study. Performance of everyday memory tasks was tested over six weeks with
the smartwatch and software provided during weeks three and four. Participants
were asked to use their usual memory aids and strategies during the control
phases (weeks 1-2, 5-6). Three participants successfully used the smartwatch
throughout the intervention weeks and gave positive usability ratings. A fourth
participant experienced a seizure and subsequently left the study before the
intervention phase. Three participants showed improved memory performance when
using the smartwatch. Nonoverlap of all pairs (NAP) analysis showed a non
significant small increase in memory performance between baseline and
intervention phases (mean NAP = 0.1, p = .84). There was a larger, significant
decline between the intervention and return to baseline (mean NAP = 0.58, p <
.01). The use of an off-the-shelf smartwatch device and software was feasible for
people with ABI in the community. It was effective compared to practice as usual,
although this was only apparent on withdrawal of the device.
PMID- 28425329
TI - Effects of ERK1/2 signal pathway on cardiomyocyte during glucose lowering.
AB - OBJECTIVE: This study investigated whether the extracellular signal-regulated
kinase 1/2 (ERK1/2) signal pathway affects cardiomyocyte apoptosis and the
expression of tumor necrosis factor (TNF-alpha) at different glucose-lowering
rates. METHODS: Cardiomyocytes of Wistar neonate rats were maintained in a medium
supplemented with 25 mmol/L glucosamine for 72 h. Then the medium was changed to
different concentrations of glucosamine, and all cells were divided into five
groups. The survival rate of cardiomyocyte was measured using the Cell Counting
Kit-8; cardiomyocyte apoptosis was measured using the flow cytometry instrument
and laser confocal microscope; TNF-alpha was measured using the enzyme-linked
immunosorbent assay; and ERK1/2 protein and phosphorylation were measured using
the Western blot. Cardiomyocyte apoptosis and TNF-alpha were measured again after
adding U0126. RESULTS: As the glucose-lowering rate increased, the survival rate
of cardiomyocytes increased in group B and decreased in groups C, D, and E. The
TNF-alpha concentration increased in groups B, C, and D and decreased in group E.
After 24 h, the apoptosis rate decreased in group B and increased in groups C, D,
and E. The expression of p-ERK1/2 increased in groups B, D, and E, and was the
lowest in group C. After adding U0126, the survival rate of cardiomyocyte in all
groups increased and TNF-alpha concentration decreased. CONCLUSIONS: The
influence of glucose-lowering rate on cardiomyocyte apoptosis and TNF-alpha was
caused by the p-ERK1/2 pathway. During the glucose-lowering course, the p-ERK1/2
pathway promoted cardiomyocyte apoptosis, and TNF-alpha secretion was related to
not only osmotic pressure but also ERK1/2 signal pathway activation.
PMID- 28425334
TI - Remifentanil for Sedation of Children With Traumatic Brain Injury.
AB - OBJECTIVE: To determine whether remifentanil would provide adequate sedation
while allowing frequent and reproducible neurologic assessments in children
admitted to the pediatric intensive care unit (PICU) with traumatic brain injury
(TBI) during mechanical ventilation. DESIGN: Retrospective review. SETTING:
Tertiary care PICU. PATIENTS: Thirty-eight patients over a 30-month period.
MEASUREMENTS AND MAIN RESULTS: Median age was 9 years (interquartile range [IQR]
2.25-12 years). The median Glasgow Coma Scale (GCS) was 9 (IQR: 8-10). All
patients were tracheally intubated and receiving mechanical ventilation. A
continuous infusion of remifentanil was started at 0.1 MUg/kg/min, and bolus
doses of 0.25 to 1 MUg/kg were administered every 3 to 5 minutes as needed to
reach the desired sedation level. Infusions were stopped at least hourly to
perform neurologic examinations. The median remifentanil dose was 0.25 MUg/kg/min
with an IQR of 0.1 and 0.6 MUg/kg/min. The maximum dose for any patient in the
cohort was 2 MUg/kg/min. Median duration of therapy with remifentanil was 20
hours (IQR: 8-44 hours). Adequate sedation was achieved with sedation scores
(State Behavioral Scale) meeting target levels with a median value of 100% of the
time (IQR: 79%-100%). Neurologic examinations were able to be performed within a
median of 9 minutes (IQR: 5-14 minutes) of pausing the infusion. No serious
safety events occurred. In 68% of the patients, neurologic examinations remained
reassuring during remifentanil infusion, and patients were extubated. The
remaining patients were transitioned to traditional sedative agents for long-term
management of their traumatic injuries once the neurologic status was deemed
stable. CONCLUSION: This data suggest that remifentanil is a suitable sedative
agent for use in children with TBI. It provides a rapid onset of sedation with
recovery that permits reliable and reproducible clinical examination.
PMID- 28425335
TI - The Incidence of and Risk Factors for Postintubation Hypotension in the
Immunocompromised Critically Ill Adult.
AB - OBJECTIVES: Our primary aim was to ascertain the frequency of postintubation
hypotension in immunocompromised critically ill adults with secondary aims of
arriving at potential risk factors for the development of postintubation
hypotension and its impact on patient-related outcomes. METHODS: Critically ill
adult patients (>=18 years) were included from January 1, 2010, to December 31,
2014. We defined immunocompromised as patients with any solid organ or nonsolid
organ malignancy or transplant, whether solid organ or not, requiring current
chemotherapy. Postintubation hypotension was defined as a decrease in systolic
blood pressure to less than 90 mm Hg or a decrease in mean arterial pressure to
less than 65 mm Hg or the initiation of any vasopressor medication. Patients were
then stratified based on development of postintubation hypotension. Potential
risk factors and intensive care unit (ICU) outcome metrics were electronically
captured by a validated data mart system. RESULTS: The final cohort included 269
patients. Postintubation hypotension occurred in 141 (52%; 95% confidence
interval: 46-58) patients. Several risk factors predicted postintubation
hypotension on univariate analysis; however, only Acute Physiology and Chronic
Health Evaluation III score in the first 24 hours, preintubation shock status,
and preintubation hemodynamic instability remained significant on all 4
multivariate analyses. Patients developing postintubation hypotension had higher
ICU and hospital mortality (54 [38%] vs 31 [24%], P = .01; 69 [49%] vs 47 [37%],
P = .04). CONCLUSION: Based on previous literature, we found a higher frequency
of postintubation hypotension in the immunocompromised than in the
nonimmunocompromised critically ill adult patients. Acute Physiology and Chronic
Health Evaluation III score in the first 24 hours, preintubation shock status,
and preintubation hemodynamic instability were significant predictors on
multivariate analyses. Postintubation hypotension led to higher ICU and hospital
mortality in those experiencing this complication.
PMID- 28425338
TI - Editorial.
PMID- 28425336
TI - Protective Efect of Brain-derived Neurotrophic Factor Against the Ototoxicity of
Pseudomonas aeruginosa Exotoxin A.
AB - Objective--The protective effect of brain-derived neurotrophic factor (BDNF)
against the ototoxicity resulting from exposure of Pseudomonas aeruginosa
exotoxin A (PaExoA) to the middle ear was analyzed. The combined effect of BDNF
and NG-nitro-L-arginine methyl ester (L-NAME) was also investigated. Material and
methods--Six groups of albino rats were instilled through the tympanic membrane
into the round window niche with the following solutions: saline; PaExoA; BDNF; L
NAME; PaExoA + BDNF; and PaExoA + BDNF + L-NAME. Frequency-specific (2-31.5 kHz)
auditory brainstem responses were used to obtain the hearing thresholds before
and 2, 5 and 15 days after instillation. Results--PaExoA penetrated from the
middle ear into the cochlea, causing initially mixed hearing loss, followed by
persistent sensorineural hearing loss. This impairment was blocked by BDNF at 6,
8 and 10 kHz on Day 2 and at 8 kHz on Day 5. L-NAME given in combination with
BDNF did not show any additional protective effect. There were no significant
differences in the thickness of the round window membrane between control ears
and those in each instillation group. Conclusion--Our results suggest that BDNF
may protect against cochlear damage caused by PaExoA in the middle turns of the
ear.
PMID- 28425344
TI - 20 Years of fish immunotoxicology - what we know and where we are.
AB - Despite frequent field observations of impaired immune response and increased
disease incidence in contaminant-exposed wildlife populations, immunotoxic
effects are rarely considered in ecotoxicological risk assessment. The aim of
this study was to review the literature on immunotoxic effects of chemicals in
fish to quantitatively evaluate (i) which experimental approaches were used to
assess immunotoxic effects, (ii) whether immune markers exist to screen for
potential immunotoxic activities of chemicals, and (iii) how predictive those
parameters are for adverse alterations of fish immunocompetence and disease
resistance. A total of 241 publications on fish immunotoxicity were
quantitatively analyzed. The main conclusions included: (i) To date, fish
immunotoxicology focused mainly on innate immune responses and immunosuppressive
effects. (ii) In numerous studies, the experimental conditions are poorly
documented, as for instance age or sex of the fish or the rationale for the
selected exposure conditions is often missing. (iii) Although a broad variety of
parameters were used to assess immunotoxicity, the rationale for the choice of
measured parameters was often not given, remaining unclear how they link to the
suspected immunotoxic mode of action of the chemicals. (iv) At the current state
of knowledge, it is impossible to identify a set of immune parameters that could
reliably screen for immunotoxic potentials of chemicals. (v) Similarly, in fish
immunotoxicology there is insufficient understanding of how and when chemical
induced modulations of molecular/cellular immune changes relate to adverse
alterations of fish immunocompetence, although this would be crucial to include
immunotoxicity in ecotoxicological risk assessment.
PMID- 28425345
TI - Surrogate marker analysis in cancer clinical trials through time-to-event
mediation techniques.
AB - The meta-analytic approach is the gold standard for validation of surrogate
markers, but has the drawback of requiring data from several trials. We refine
modern mediation analysis techniques for time-to-event endpoints and apply them
to investigate whether pathological complete response can be used as a surrogate
marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3
trial in which locally advanced breast cancer patients were randomised to either
taxane or anthracycline based neoadjuvant chemotherapy. In the mediation
analysis, the treatment effect is decomposed into an indirect effect via
pathological complete response and the remaining direct effect. It shows that
only 4.2% of the treatment effect on disease-free survival after five years is
mediated by the treatment effect on pathological complete response. There is thus
no evidence from our analysis that pathological complete response is a valuable
surrogate marker to evaluate the effect of taxane versus anthracycline based
chemotherapies on progression free survival of locally advanced breast cancer
patients. The proposed analysis strategy is broadly applicable to mediation
analyses of time-to-event endpoints, is easy to apply and outperforms existing
strategies in terms of precision as well as robustness against model
misspecification.
PMID- 28425346
TI - Ambrisentan: a review of its use in pulmonary arterial hypertension.
AB - Pulmonary arterial hypertension (PAH) is a progressive disease defined by an
elevation in pulmonary arterial pressure that can lead to right heart failure and
death. Ambrisentan is a selective endothelin receptor antagonist approved for the
treatment of idiopathic, heritable PAH and connective tissue disease-associated
PAH. Ambrisentan has been shown to improve exercise capacity and hemodynamics
with an acceptable side-effect profile. It has also proven to be safely used in
combination with other PAH-specific medications, especially with
phosphodiesterase-5 inhibitors. In the recent randomized trial, AMBITION, it was
shown that upfront combination therapy of ambrisentan and tadalafil significantly
decreased the risk of clinical failure compared with monotherapy. This review
describes the drug profile of ambrisentan and its safety and efficacy in the
treatment of PAH.
PMID- 28425347
TI - Expression and Clinicopathological Significance of Mel-18 and Bmi-1 in Esophageal
Squamous Cell Carcinoma.
AB - The Polycomb group genes are a general class of regulators that are responsible
for maintaining homeotic gene expression throughout cell division. Polycomb group
expression plays an important role in oncogenesis of several types of human
cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus
insert site 1 are key Polycomb group proteins. Studies have shown that melanoma
nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney
leukemia virus insert site 1 is overexpressed in several human malignancies.
However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney
leukemia virus insert site 1 in esophageal squamous cell carcinoma are still
unclear. In this study, we analyzed the expression levels of melanoma nuclear
protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89
esophageal cancer tissues and paired normal mucosal tissues using
immunohistochemistry, Western blotting, and quantitative real-time polymerase
chain reaction analyses. We found that the expression of melanoma nuclear protein
18 in the carcinoma tissues was significantly lower than that in the noncancerous
mucosal tissues ( P < .05), and B-cell-specific Moloney leukemia virus insert
site 1 expression in the carcinoma tissues was significantly higher than that in
the noncancerous mucosal tissues ( P < .05). In addition, the expression of
melanoma nuclear protein 18 was correlated with clinical stage, depth of
invasion, and lymph node metastasis ( P < .05) but was not correlated with
gender, age, degree of differentiation, or disease-free survival ( P > .05). B
cell-specific Moloney leukemia virus insert site 1 expression was strongly
correlated with the degree of differentiation, clinical stage, and lymph node
metastasis ( P <.05) but was not correlated with the gender, age, depth of
invasion or disease-free survival ( P > .05). Moreover, there was a negative
correlation between melanoma nuclear protein 18 and B-cell-specific Moloney
leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma (
P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific
Moloney leukemia virus insert site 1 may play a crucial role in esophageal
squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney
leukemia virus insert site 1 may be a potential biomarker for diagnosis and
prognosis of esophageal squamous cell carcinoma.
PMID- 28425348
TI - Integration of Functional MRI and White Matter Tractography in CyberKnife
Radiosurgery.
AB - PURPOSE: To investigate the efficacy of the integration of functional magnetic
resonance imaging and diffusion-tensor imaging tractography data into CyberKnife
radiosurgery for intracranial tumor management. MATERIALS AND METHODS: Functional
neuroimaging, anatomical magnetic resonance imaging, and computed tomography
images of patients with brain lesions in critical areas were acquired before
radiosurgery. The acquired data sets were coregistered using the MIM image fusion
software module and then were imported into the CyberKnife Robotic Radiosurgery
System (Multiplan 4.0.2) for delineating the target, organs at risk, and possible
nearby functionally relevant cortical and subcortical areas. Radiation dose
distributions with and without the functionally relevant cortical and subcortical
areas into the optimization process were developed and compared. RESULTS: There
were significant differences between the treatment plans with and without the
functionally relevant cortical and subcortical areas into the optimization
process. An average 22.71% reduction in the maximum dose to functional areas was
observed. No neurological complication due to radiation damage was observed in
the follow-up period. CONCLUSION: The functional neuroimaging could be easily and
reliably integrated into the CyberKnife treatment planning. Consideration of
functional structures and fiber tracts during treatment planning could clinically
reduce the radiation doses to these critical structures, thereby preserving its
unique function of brain.
PMID- 28425349
TI - Clinical characteristics of unknown symptom onset stroke patients with and
without diffusion-weighted imaging and fluid-attenuated inversion recovery
mismatch.
AB - Background Diffusion-weighted imaging (DWI) and fluid-attenuated inversion
recovery (FLAIR) mismatch was suggested to identify stroke patients with unknown
time of symptom onset likely to be within the time window for thrombolysis. Aims
We aimed to study clinical characteristics associated with DWI-FLAIR mismatch in
patients with unknown onset stroke. Methods We analyzed baseline MRI and clinical
data from patients with acute ischemic stroke proven by DWI from WAKE-UP, an
investigator-initiated, randomized, placebo-controlled trial of MRI-based
thrombolysis in stroke patients with unknown time of symptom onset. Clinical
characteristics were compared between patients with and without DWI-FLAIR
mismatch. Results Of 699 patients included, 418 (59.8%) presented with DWI-FLAIR
mismatch. A shorter delay between last seen well and symptom recognition (p =
0.0063), a shorter delay between symptom recognition and arrival at hospital (p =
0.0025), and history of atrial fibrillation (p = 0.19) were predictors of DWI
FLAIR mismatch in multivariate analysis. All other characteristics were
comparable between groups. Conclusions There are only minor differences in
measured clinical characteristics between unknown symptom onset stroke patients
with and without DWI-FLAIR mismatch. DWI-FLAIR mismatch as an indicator of stroke
onset within 4.5 h shows no relevant association with commonly collected clinical
characteristics of stroke patients. Clinical Trial Registration URL:
http://www.clinicaltrials.gov . Unique identifier: NCT01525290; URL:
https://www.clinicaltrialsregister.eu . Unique identifier: 2011-005906-32.
PMID- 28425351
TI - Metabolic changes in methomyl poisoned rats treated by vitamin E.
AB - In this study, we developed a serum and urine metabolomic method based on gas
chromatography-mass spectrometry (GC-MS) combination with biomedical results to
evaluate the effect of vitamin E treatment on methomyl poisoning rats. The rats
were divided into three groups: the control group, methomyl poisoning group, and
vitamin E treatment group. Partial least squares discriminate analysis (PLS-DA)
showed that methomyl poisoning induced metabolic perturbations. Compared to the
control group, based on the urinary metabolomics data, the level of ribitol, l
proline, xylitol, hydrocinnamic acid, 11-cis-octadecenoic acid, octadecanoic
acid, and hexadecanoic acid of methomyl poisoning group increased, while the
level of 2,3,4-trihydroxybutyric acid, ethanimidic acid, pantothenic acid, and
retinoic acid decreased. Vitamin E pretreatment effectively normalized the levels
of metabolites in rat urine in vitamin E treatment group. There was no
significant difference in rat plasma metabolomic data after acute methomyl
poisoning. The results indicate that metabolomic method based on GC-MS may be
useful to elucidate the vitamin E treatment for methomyl poisoning.
PMID- 28425350
TI - Metabolomics approach discriminates toxicity index of pyrazinamide and its
metabolic products, pyrazinoic acid and 5-hydroxy pyrazinoic acid.
AB - Pyrazinamide (PYZ)-an essential component of primary drug regimen used for the
treatment and management of multidrug resistant or latent tuberculosis-is well
known for its hepatoxicity. However, the mechanism of PYZ-induced hepatotoxicity
is still unknown to researchers. Studies have shown that the drug is metabolized
in the liver to pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OHPA) which
individually may cause different degrees of hepatotoxicity. To evaluate this
hypothesis, PYZ, PA, and 5-OHPA were administered to albino Wistar rats orally
(respectively, at 250, 125, and 125 mg kg-1 for 28 days). Compared to normal
rats, PYZ and its metabolic products decreased the weights of dosed rats and
induced liver injury and a status of oxidative stress as assessed by combined
histopathological and biochemical analysis. Compared to normal controls, the
biochemical and morphological changes were more aberrant in PA- and 5-OHPA-dosed
rats with respect to those dosed with PYZ. Finally, the serum metabolic profiles
of rats dosed with PYZ, PA, and 5-OHPA were measured and compared with those of
normal control rats. With respect to normal control rats, the rats dosed with PYZ
and 5-OHPA showed most aberrant metabolic perturbations in their sera as compared
to those dosed with PA. Altogether, the study suggests that PYZ-induced
hepatotoxicity might be associated with its metabolized products, where 5-OHPA
contributes to a higher degree in its overall toxicity than PA.
PMID- 28425352
TI - Overdose in young children treated with anti-reflux medications: Poisons enquiry
evidence of excess 10-fold dosing errors with ranitidine.
AB - BACKGROUND: Accidental drug overdose is a common problem in young children. We
examined the influence of formulation and dose in enquiries for different gastro
oesophageal reflux disease treatments in children under 5 years to the UK's
National Poisons Information Service. METHODS: Overdose characteristics with
ranitidine, omeprazole or domperidone were compared with those of metoclopramide
and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June
2015. RESULTS: There were a total of 1092 ranitidine, 618 domperidone and 1193
omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of
these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole
cases occurred in children <5 years. In comparison, 17% (34/424) of
metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517)
of ranitidine overdose enquiries in children <5 years were under 6 months of age,
higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%),
chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In
children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine.
CONCLUSIONS: Tenfold overdoses in children (<5 years) were a feature of
ranitidine enquiries, likely due to the high concentration of the syrup. This has
relevance to other liquid formulations used for non-licenced indications in young
children. Such therapeutic errors cause significant carer anxiety and healthcare
utilization. Assistance is needed from manufacturers and legislators in modifying
formulation so that drugs can be safely used in young children. Education of
prescribers and carers is also needed to reduce the incidence of such errors that
cause significant carer anxiety and healthcare utilization.
PMID- 28425361
TI - Assessment of real-time PCR cycle threshold values in Microsporum canis culture
positive and culture-negative cats in an animal shelter: a field study.
AB - Objectives Real-time PCR provides quantitative information, recorded as the cycle
threshold (Ct) value, about the number of organisms detected in a diagnostic
sample. The Ct value correlates with the number of copies of the target organism
in an inversely proportional and exponential relationship. The aim of the study
was to determine whether Ct values could be used to distinguish between culture
positive and culture-negative samples. Methods This was a retrospective analysis
of Ct values from dermatophyte PCR results in cats with suspicious skin lesions
or suspected exposure to dermatophytosis. Results One hundred and thirty-two
samples were included. Using culture as the gold standard, 28 were true
positives, 12 were false positives and 92 were true negatives. The area under the
curve for the pretreatment time point was 96.8% (95% confidence interval [CI]
94.2-99.5) compared with 74.3% (95% CI 52.6-96.0) for pooled data during
treatment. Before treatment, a Ct cut-off of <35.7 (approximate DNA count 300)
provided a sensitivity of 92.3% and specificity of 95.2%. There was no reliable
cut-off Ct value between culture-positive and culture-negative samples during
treatment. Ct values prior to treatment differed significantly between the true
positive and false-positive groups ( P = 0.0056). There was a significant
difference between the pretreatment and first and second negative culture time
points ( P = 0.0002 and P <0.0001, respectively). However, there was substantial
overlap between Ct values for true positives and true negatives, and for pre- and
intra-treatment time points. Conclusions and relevance Ct values had limited
usefulness for distinguishing between culture-positive and culture-negative cases
when field study samples were analyzed. In addition, Ct values were less reliable
than fungal culture for determining mycological cure.
PMID- 28425362
TI - To be or not to be: Stuttering and the human costs of being "un-disabled".
AB - PURPOSE: The centrality of communicating in human life means that communication
difficulties are experienced at a deeply personal level and have significant
implications for identity. Intervention methods may interact positively or
negatively with these experiences. METHOD: This paper explores this intersection
in the case of stuttering, suggesting that some intervention styles may dovetail
unhelpfully with the "mainstream" prizing of normalcy. In particular, most
"western" societies offer a performance-oriented milieu which prizes efficiency,
immediacy and competitiveness, diverting energy from the equally important work
of understanding and integrating difference. RESULT: Given that a person who
stutters speaks fluently and with a stutter, stuttering can lean toward a complex
view of disability identity-being both able and disabled. This split repertoire
invites psychologically costly efforts at being "un-disabled". CONCLUSION:
Interventions which amplify this tendency can contribute to an alienation from
self amid strivings for normalcy.
PMID- 28425363
TI - Language functioning, mental health and alexithymia in incarcerated young
offenders.
AB - PURPOSE: Previous studies describe high rates of language impairment in young
offenders; however, important correlates such as mental health status and
alexithymia have received little attention. METHOD: This study describes a cross
sectional study of the language, emotion recognition and mental health of 100
young people completing custodial sentences in New South Wales (Australia). The
sample comprised 70 young people from non-indigenous backgrounds (n = 60 male)
and 30 from indigenous backgrounds (n = 25 male). The mean age of the sample was
17.1 years. It was hypothesized that, in addition to elevated rates of language
impairment, alexithymia would be over-represented in this group. It was further
predicted that impoverished language skills would contribute to alexithymia
scores. RESULT: Only a quarter of the sample overall achieved Clinical Evaluation
of Language Fundamentals (CELF-4) Core Language Scores in the expected range;
rates of language impairment were higher in indigenous males than in non
indigenous males and in the females. Alexithymia was present in 59% of the
sample, but appeared to be associated with poor mental health, rather than with
language impairment. CONCLUSION: Interventions for young offenders (e.g.
psychological counselling, restorative justice conferencing) should be framed
around these difficulties. Validated language measures for use with young
indigenous offenders are needed.
PMID- 28425365
TI - Parental directiveness and responsivity toward young children with complex
communication needs.
AB - PURPOSE: The aim of the present study was to determine if parent responsiveness
to their children with complex communication needs (CCN) during naturalistic play
changed over an 18-month period and determine if any such changes were influenced
by the child's overall level of receptive and expressive language development,
motor development or differing play contexts. This longitudinal information is
important for early intervention speech-language pathologists and parents of
children with developmental disabilities for whom the use of parent-directed
responsivity interventions may be encouraged. METHOD: Over an 18-month period, 37
parents of young children who had physical and/or neurological disabilities
participated in three home-based parent-child play episodes. Videotapes of each
play episode were extracted and coded. RESULT: Results indicated parents who were
initially responsive showed a significant tendency to continue to be so. Early
on, parents were significantly more likely to be directive during object play
than social play and significantly more likely to interact responsively during
social play than object play. CONCLUSION: Parents of children with developmental
disabilities were not consistently less responsive to their children based on
motor or language capabilities. Previous reports of higher parental directiveness
with children who have developmental disabilities may be attributable to object
based play interactions.
PMID- 28425364
TI - Long-term effects of an intensive voice treatment for vocal fold nodules.
AB - PURPOSE: The purpose of the current study was to examine the long-term effects of
intensive voice treatment for vocal fold nodules, compared to outcomes for
patients treated with traditional voice therapy. It was hypothesised that
intensive treatment would provide comparable maintenance of vocal function, voice
quality, and patients' perception of quality-of-life when compared with
traditional treatment at 6 month follow-up. METHOD: Thirty-six women diagnosed
with bilateral vocal fold nodules who were treated with either traditional (n =
20; once a week for 8 weeks) or intensive (n = 16; eight sessions within 3 weeks)
therapy. Each participant completed voice, stroboscopic, and acoustic assessments
and the Voice Handicap Index before, immediately post and 6 months post
treatment. RESULT: Results revealed most improved perceptual, stroboscopic and
acoustic parameters were maintained in both groups at 6 months post-treatment,
with no significant differences between the two groups. In addition, both groups
maintained satisfaction on their perception of vocal function, with no
significant difference between the two groups. CONCLUSION: The investigation
provided further evidence that individuals with vocal fold nodules are able to
maintain improved voice quality and vocal health following intensive voice
treatment to a similar degree to traditional voice treatment.
PMID- 28425366
TI - Expressive and receptive language skills in preschool children from a socially
disadvantaged area.
AB - PURPOSE: Evidence suggests that children present with receptive language skills
that are equivalent to or more advanced than expressive language skills. This
profile holds true for typical and delayed language development. This study aimed
to determine if such a profile existed for preschool children from an area of
social deprivation and to investigate if particular language skills influence any
differences found between expressive and receptive skills. METHOD: Data from 187
CELF P2 UK assessments conducted on preschool children from two socially
disadvantaged areas in a city in southern Ireland. RESULT: A significant
difference was found between Receptive Language Index (RLI) and Expressive
Language Index (ELI) scores with Receptive scores found to be lower than
Expressive scores. The majority (78.6%) of participants had a lower Receptive
Language than Expressive score (RLI < ELI), 18.2% of participants had a higher
Receptive score than score (RLI > ELI), with very few (3.2%) having the same
Receptive and Expressive scores (RLI = ELI). Scores for the Concepts and
Following Directions (receptive) sub-test were significantly lower than for the
other receptive sub tests, while scores for the Expressive Vocabulary sub-test
were significantly higher than for the other expressive sub tests. CONCLUSION:
The finding of more advanced expressive than receptive language skills in
socially deprived preschool children is previously unreported and clinically
relevant for speech-language pathologists in identifying the needs of this
population.
PMID- 28425367
TI - Comparing alternate learning pathways within a problem-based learning speech
language pathology curriculum.
AB - PURPOSE: This qualitative study investigated the learning process for speech
language pathology (SLP) students engaging in a problem-based learning (PBL)
curriculum and compared the perspectives of students from two pathways. METHOD:
Sixteen final-year SLP students participated in one of four focus groups. Half
the participants entered the course directly via an undergraduate pathway and the
other half entered via a graduate entry pathway. Each focus group comprised two
students from each pathway. Data were generated via a semi-structured interview
and analysed thematically. RESULT: Regardless of participants' pathway, many
similar themes about factors that influenced their expectations prior to PBL
commencing as well as their actual PBL experiences were raised. Participants
believed that PBL was a productive way to learn and to develop clinical
competencies. Many were critical of variations in PBL facilitation styles and
were sensitive to changes in facilitators. The majority of participants viewed
experiential opportunities to engage in PBL prior to commencement of semester as
advantageous. CONCLUSION: Combining students with different backgrounds has many
advantages to the PBL learning process. Regardless of prior experiences, all
students must be sufficiently prepared. Furthermore, the facilitator has a
crucial role with the potential to optimise or detract from the learning
experience.
PMID- 28425368
TI - The relationship between labial vibrotactile detection and pure-tone hearing
thresholds in healthy, ageing adults.
AB - PURPOSE: Orofacial anatomy is unique from other body systems in that oral
musculature inserts directly into the underlying cutaneous skin, allowing for
tight temporal synchronicity between somatosensory and auditory performance
feedback to maintain correct orofacial behaviours across the lifespan.
Unfortunately, little is currently known regarding the changes in orofacial
sensory capacities associated with ageing and how these somatosensory and
auditory changes may impact feedback during functional behaviours such as speech
or swallowing. The purpose of this descriptive study was to begin assessing the
relationship between the auditory and labial somatosensory system in healthy
ageing adults. METHOD: Pure-tone hearing thresholds were determined for 500,
1000, 2000 and 4000 Hz. Using a 2-alternative forced choice paradigm, 60 adults
(19-84 years) completed vibrotactile detection thresholds (VDT) at the 5 and 10
Hz test frequencies. RESULT: A significant difference for age by group was
identified at the 5 Hz test frequency. Spearman Correlations identified a
significant correlation between age and pure tone hearing thresholds and the 5 Hz
test frequency threshold. CONCLUSION: A relationship between pure tone hearing
thresholds and labial somatosensory was identified. Future studies will begin the
processing of modelling the complex multivariate sensorimotor relationship in
healthy individuals before moving to a disordered population.
PMID- 28425373
TI - Calm child programme: Parental programme for anxiety in children and young people
with autism spectrum disorder and intellectual disabilities.
AB - Children with autism spectrum disorder (ASD) and intellectual disabilities (IDs)
are more vulnerable to experiencing anxiety disorders. Parental involvement in
intervention is crucial for successful management of the interventions in the
population of people with ASDs. This article describes the design and evaluation
of parenting programme for anxiety disorders in children and young people with
ASD and ID. In phase 1 semi-structured interviews were conducted to explore
management strategies for anxiety at home and in school settings. A total of 34
participants (14 parents, 20 teachers) participated in the interviews. A Delphi
process was conducted with health professionals to develop consensus on
appropriate anxiety interventions. In phase 2 the intervention programme was
implemented by seven parents who also participated in focus group to evaluate the
developed programme. A parental programme, calm child programme (CCP), was
developed, implemented and evaluated. The evaluations show significant decrease
in children's anxiety as a result of implementing the programme. This study
contributes further evidence to parental involvement in interventions for
children and young people with ASD and IDs. The CCP is a useful and cost
effective approach in enabling parents to provide anxiety interventions in a home
setting.
PMID- 28425386
TI - 22nd Annual RIMS Conference 2017.
PMID- 28425387
TI - Zebra-borne neurotropic equid herpesvirus 1 meningoencephalitis in a Thomson's
gazelle ( Eudorcas thomsonii).
AB - We describe the histopathologic, immunohistochemical, and molecular features of a
case of meningoencephalitis in a Thomson's gazelle ( Eudorcas thomsonii)
naturally infected with zebra-borne equid herpesvirus 1 (EHV-1) and the
implications for the molecular detection of zebra-borne EHV-1. A 4-y-old female
Thomson's gazelle was submitted for postmortem examination; no gross
abnormalities were noted except for meningeal congestion. Microscopic evaluation
demonstrated multifocal nonsuppurative meningoencephalitis with intranuclear
eosinophilic and amphophilic inclusion bodies and EHV-9 antigen in neurons. PCR
demonstrated the presence of a herpesvirus with a nucleotide sequence 99-100%
identical to the corresponding sequences of zebra-borne EHV-1 and of EHV-9
strains. To determine whether EHV-1 or EHV-9 was involved, a PCR with a specific
primer set for EHV-9 ORF59/60 was used. The sequence was identical to that of 3
recognized zebra-borne EHV-1 strains and 91% similar to that of EHV-9. This
isolate was designated as strain LM2014. The partial glycoprotein G ( gG) gene
sequence of LM2014 was also identical to the sequence of 2 zebra-borne EHV-1
strains (T-529 isolated from an onager, 94-137 from a Thomson's gazelle). The
histologic lesions of encephalitis and antigen localization in this gazelle
indicate prominent viral neurotropism, and lesions were very similar to those
seen in EHV-1- and EHV-9-infected non-equid species. Histologic lesions caused by
EHV-9 and zebra-borne EHV-1 are therefore indistinguishable.
PMID- 28425388
TI - Lower Bound on Estimation Variance of the Ultrasonic Attenuation Coefficient
Using the Spectral-Difference Reference-phantom Method.
AB - Ultrasonic attenuation is one of the primary parameters of interest in
Quantitative Ultrasound (QUS). Non-invasive monitoring of tissue attenuation can
provide valuable diagnostic and prognostic information to the physician. The
Reference Phantom Method (RPM) was introduced as a way of mitigating some of the
system-related effects and biases to facilitate clinical QUS applications. In
this paper, under the assumption of diffuse scattering, a probabilistic model of
the backscattered signal spectrum is used to derive a theoretical lower bound on
the estimation variance of the attenuation coefficient using the Spectral
Difference RPM. The theoretical lower bound is compared to simulated and
experimental attenuation estimation statistics in tissue-mimicking (TM) phantoms.
Estimation standard deviation (STD) of the sample attenuation in a region of
interest (ROI) of the TM phantom is measured for various combinations of
processing parameters, including Radio-Frequency (RF) data block length (i.e.,
window length) from 3 to 17 mm, RF data block width from 10 to 100 A-lines, and
number of RF data blocks per attenuation estimation ROI from 3 to 10. In addition
to the Spectral-Difference RPM, local attenuation estimation for simulated and
experimental data sets was also performed using a modified implementation of the
Spectral Fit Method (SFM). Estimation statistics of the SFM are compared to
theoretical variance predictions from the literature.1 Measured STD curves are
observed to lie above the theoretical lower bound curves, thus experimentally
verifying the validity of the derived bounds. This theoretical framework benefits
tissue characterization efforts by isolating processing parameter ranges that
could provide required precision levels in estimation of the ultrasonic
attenuation coefficient using Spectral Difference methods.
PMID- 28425389
TI - Simultaneous Analysis of Simple Coumarins and Furocoumarines in Cigarettes by
Solid-Phase Extraction with Gas Chromatography-Mass Spectrometry.
AB - A sensitive, high-throughput analytical method based on a GC-MS method was
established for the simultaneous quantitative determination of two categories of
harmful coumarins: simple coumarins (coumarin, 6-methylcoumarin, 7
methoxycoumarin, 3,4-dihydrocoumarin, and 7-ethoxy-4-methylcoumarin) and
furocoumarines (psoralen, 8-methoxypsoralen, 5-methoxypsoralen, and trioxysalen).
The nine analytes were extracted with ethyl acetate, purified with Oasis HLB
solid-phase extraction (SPE) cartridges, and identified and quantitatively
determined by GC-MS in selected-ion monitoring mode. The LODs and LOQs of these
compounds were in the ranges of 12.5-21.2 and 41.6-70.0 MUg/kg, respectively.
Average recoveries for the nine analytes ranged from 72.7 to 86.6% at LOQ, 1.5*
LOQ, and 2* LOQ spike levels, with RSDs that were typically lower than 5.1%. The
SPE-GC-MS method developed in this study was initially applied to research
coumarins in cigarette samples; it proved to be accurate, sensitive, convenient,
and practical.
PMID- 28425391
TI - New Analytical Applications for Food Antigens.
PMID- 28425392
TI - An Improved Method for the Quantification of Thiamine (Vitamin B1) in Cocoa
Containing Beverage Powders.
AB - The purpose of this work was to understand low recoveries of thiamine (vitamin
B1) when extracted from cocoa-containing beverage powders fortified with water
soluble vitamin B1, and to develop and validate a new procedure to improve these
results. Based on the literature, previous trials have focused on two main
factors: pH value prior to paper filtration and the need for solid-phase
extraction (SPE) clean up. We demonstrate that by following European Standard EN
14122, recovery of thiamine in cocoa-containing beverage powders is low and
dependent on the test portion (86 and 72% for 0.5 and 1.5 g test portions,
respectively). Our improved method resolved this problem by keeping the pH low
(around 1) prior to paper filtration, leading to a 96.3% recovery and high
precision (RSDr of 3.5%). The use of strong cation-exchange SPE cartridges for
cleanup prior to the thiamine oxidation reaction proved to be essential. A
comparison between our improved method and EN 14122 on nine cocoa-containing
beverage samples available on local market from different manufacturers showed a
systematic increase in thiamine content (up to 70%) when the improved method was
applied. The highest difference was observed for the sample that contained the
highest amount of cocoa. However, for beverage powders that contained both cocoa
and milk, no difference was observed.
PMID- 28425393
TI - Magnetic Graphene Oxide as an Efficient Adsorbent for the Separation and
Preconcentration of Cu(II), Pb(II), and Cd(II) from Environmental Samples.
AB - The separation and preconcentration of copper(II), lead(II), and cadmium(II) ions
on magnetic graphene oxide (MGO) by solid-phase extraction was carried out.
Quantitative recovery was obtained by adsorption of analytes on MGO at pH 6 and
elution of 3 M HNO3 in 10% acetone. To optimize the presented method, the effects
of various parameters-including pH, eluent conditions, and vortex time-were
examined. Matrix effects were also investigated. Mean recoveries of the analytes
were between 95 and 105%. The proposed method was validated by applying it to
certified reference materials. Addition and recovery tests were also performed.
The method was applied to verify the analyte content of several water and food
samples.
PMID- 28425394
TI - Near-Infrared Spectrum Detection of Wheat Gluten Protein Content Based on a
Combined Filtering Method.
AB - To eliminate the random error of the derivative near-IR (NIR) spectrum and to
improve model stability and the prediction accuracy of the gluten protein
content, a combined method is proposed for pretreatment of the NIR spectrum based
on both empirical mode decomposition and the wavelet soft-threshold method. The
principle and the steps of the method are introduced and the denoising effect is
evaluated. The wheat gluten protein content is calculated based on the denoised
spectrum, and the results are compared with those of the nine-point smoothing
method and the wavelet soft-threshold method. Experimental results show that the
proposed combined method is effective in completing pretreatment of the NIR
spectrum, and the proposed method improves the accuracy of detection of wheat
gluten protein content from the NIR spectrum.
PMID- 28425396
TI - Development and Single-Laboratory Validation of a Liquid Chromatography Tandem
Mass Spectrometry Method for Quantitation of Tetrodotoxin in Mussels and Oysters.
AB - In recent years, evidence has grown for the presence of tetrodotoxin (TTX) in
bivalve mollusks, leading to the potential for consumers of contaminated products
to be affected by Tetrodotoxin Shellfish Poisoning (TSP). A single-laboratory
validation was conducted for the hydrophilic interaction LC (HILIC) tandem MS
(MS/MS) analysis of TTX in common mussels and Pacific oysters-the bivalve species
that have been found to contain TTXs in the United Kingdom in recent years. The
method consists of a single-step dispersive extraction in 1% acetic acid,
followed by a carbon SPE cleanup step before dilution and instrumental analysis.
The full method was developed as a rapid tool for the quantitation of TTX, as
well as for the associated analogs 4-epi-TTX; 5,6,11-trideoxy TTX; 11-nor TTX-6
ol; 5-deoxy TTX; and 4,9-anhydro TTX. The method can also be run as the
acquisition of TTX together with paralytic shellfish toxins. Results demonstrated
acceptable method performance characteristics for specificity, linearity,
recovery, ruggedness, repeatability, matrix variability, and within-laboratory
reproducibility for the analysis of TTX. The LOD and LOQ were fit-for-purpose in
comparison to the current action limit for TTX enforced in The Netherlands. In
addition, aspects of method performance (LOD, LOQ, and within-laboratory
reproducibility) were found to be satisfactory for three other TTX analogs (11
nor TTX-6-ol, 5-deoxy TTX, and 4,9-anhydro TTX). The method was found to be
practical and suitable for use in regulatory testing, providing rapid turnaround
of sample analysis. Plans currently underway on a full collaborative study to
validate a HILIC-MS/MS method for paralytic shellfish poisoning toxins will be
extended to include TTX in order to generate international acceptance, ultimately
for use as an alternative official control testing method should regulatory
controls be adopted.
PMID- 28425397
TI - Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients
Treated with Ledipasvir/Sofosbuvir Plus Ribavirin Pretransplant.
PMID- 28425398
TI - Prospective Indian Study of DILI with Confirmed Causality Using the Roussel Uclaf
Causality Assessment Method (RUCAM): A report of Excellence.
PMID- 28425399
TI - Liver Transplantation as Cure of Hepatocellular Carcinoma: It is not a Matter of
Time, it is a Matter of Tumor Biology.
PMID- 28425400
TI - The Direct-Acting Antivirals for Hepatitis C Virus and the Risk for
Hepatocellular Carcinoma.
AB - The increase of incidences of Hepatocellular Carcinoma (HCC) will continue in the
next decades. The therapies about hepatitis C infection has been questioned as a
risk factor. Some authors emphasized that sustained virologic response (SVR) with
interferon-based therapy reduced the risk of developing HCC. In contrast, some
publications that to suggest an increasing risk of HCC in patients treated with
Direct-Acting Antivirals (DAA). Whether these therapies are associated with an
increased risk of HCC remains to be studied and continued long-term observational
studies will be needed. The goal in HCV care needs to go beyond merely achieving
an SVR.
PMID- 28425401
TI - MRE in NAFLD: Promising but Further Validation is Required.
AB - MR elastography is a novel method for non-invasive fibrosis assessment, not yet
sufficiently validated. In a recent study in 104 patients Park, Gastroenterology
2017; 152: 598-602), MRE was compared to transient elastography for the diagnosis
of fibrosis is nonalcoholic fatty liver disease. The current viewpoint critically
appraises this study.
PMID- 28425402
TI - What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the
Liver. Is There Any Place for Surgery?
AB - Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in
the vast majority of the cases in young women. FNH represents a polyclonal lesion
characterized by local vascular abnormalities and is a truly benign lesion
without any potential for malignant transformation. A retrospective single
institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review
of studies reporting surgical therapy of overall 293 patients with FNH was
performed. Indications for resection with a focus on diagnostic workup, patient
selection, surgical mode and operative mortality and morbidity have been
analysed. Ninety three patients underwent elective hepatectomy and 134 patients
observation alone, where median follow-up was 107 months. Postoperative
complications were recorded in 14 patients, 92% of patients reported an
improvement with respect to their symptoms. Overall among 293 patients underwent
surgery in the series, included to this review, there was a morbidity of 13%,
where median follow-up was 53 months. Systematic follow-up remains the gold
standard in asymptomatic patients with FNH. However elective surgery should be
considered in symptomatic patients, in those with marked enlargement and in case
of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low
morbidity and very good long term results as far as quality of life after surgery
is concerned and surely an integral part of the modern management of FNH.
PMID- 28425403
TI - The Prevalence of Parkinson Disease Among Patients With Hepatitis C Infection.
AB - INTRODUCTION: HCV has been suspected to potentially cause degenerations in the
central nervous system. Parkinson's disease is the second most common
neurodegenerative disorder. Our aim was to assess the prevalence of Parkinson's
disease among patients with HCV infection. MATERIAL AND METHODS: For this study,
we used Medicare database from 2005-2010. Medicare database contains information
on enrollment, coverage, diagnosis recorded with International Classification of
Disease, Ninth Revision (ICD-9). From combined inpatient and outpatient files,
Parkinson's disease was identified as the first diagnosis by ICD-9 code 332.0.
Other study variables were; age, gender, race (White and No White), and Medicare
eligibility status. Simple distribution comparison by HCV status examined with t
test for numerical variables and ?2 test for categorical variables in the main
analytical cohort as well as in the propensity score matched cohort. RESULTS: A
total of 1,236,734 patients (median age 76 years, 41% male, and 85% White) was
identified among over 47 million claims. Of these, 6040 patients (0.5%) were
infected with HCV. Overall, 0.8% (N = 49) of the HCV group and 1.3% (N = 16,004)
of the Non-HCV group had Parkinson's disease (P < 0.001). When the study groups
matched for age, gender and race, the prevalence of Parkinson's disease was
similar between HCV and Non-HCV groups (P > 0.05). DISCUSSION: This study
revealed that, among Medicare population, HCV was not associated with Parkinson
disease.
PMID- 28425404
TI - Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in
Hepatitis C: A Meta-Analysis.
AB - BACKGROUND AND RATIONALE: Many different non-invasive methods have been studied
with the purpose of staging liver fibrosis. The objective of this study was
verifying if transient elastography is superior to aspartate aminotransferase to
platelet ratio index for staging fibrosis in patients with chronic hepatitis C.
MATERIAL AND METHODS: A systematic review with meta-analysis of studies which
evaluated both non-invasive tests and used biopsy as the reference standard was
performed. A random-effects model was used, anticipating heterogeneity among
studies. Diagnostic odds ratio was the main effect measure, and summary receiver
operating characteristic curves were created. A sensitivity analysis was planned,
in which the meta-analysis would be repeated excluding each study at a time.
RESULTS: Eight studies were included in the meta-analysis. Regarding the
prediction of significant fibrosis, transient elastography and aspartate
aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95%
confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94)
respectively. Concerning the prediction of cirrhosis, transient elastography and
aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of
66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval
= 4.88-11.43) respectively. CONCLUSION: In conclusion, there was no evidence of
significant superiority of transient elastography over aspartate aminotransferase
to platelet ratio index regarding the prediction of significant fibrosis, but the
former proved to be better than the latter concerning prediction of cirrhosis.
PMID- 28425405
TI - Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAg-Positive
and -Negative Chronic Hepatitis B.
AB - INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and
healthcare costs. Virologic response achieved with antivirals is associated with
progression avoidance. This study aimed to estimate the efficiency and clinical
impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov
model estimated lifetime complications and direct costs in both, HBeAg-positive
and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2
(100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir
or entecavir, were compared to no treatment. Progression was based on HBV-DNA
levels. Rescue therapy with oral antivirals was applied for peg-IFN failure.
Disease costs (C, 2014) and utilities were obtained from literature. RESULTS:
Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive,
2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg
positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128
and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and
up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost
increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg
positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio
was estimated versus the natural history for both strategies. In conclusion,
increasing antiviral coverage would be efficient, reducing complications.
PMID- 28425406
TI - Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus
Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy.
AB - INTRODUCTION: Interferon-free, multi-direct acting antiviral (DAA) therapy for
chronic hepatitis C virus (HCV) infection is highly effective and well tolerated,
but costly. To gain perspective on the evolving economics of HCV therapy, we
compared the cost per cure of a multi-DAA regimen with the prior standard of
triple therapy. MATERIAL AND METHODS: Patients infected with HCV genotype 1 who
were treated through the University of Colorado Hepatology Clinic between May
2011 and December 2014 comprised the study population. The multi-DAA regimen of
simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen
consisting of peginterferon and ribavirin, with either boceprevir or telaprevir
(TT). Sustained-virologic response (SVR) rates, total costs per treatment and
adverse events were recorded. Total cost per SVR were compared for the two
treatments, controlling for patient demographics and clinical characteristics.
RESULTS: One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n =
113). Patients receiving SMV/SOF were older, more treatment experienced, and had
a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per
patient were $152,775 and $95,943, and average total costs per SVR were $178,237
vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs
accounted for 98% of SMV/SOF and 85% of TT treatment costs. CONCLUSION: The high
cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs,
such that the cost per cure from TT to multi-DAA therapy has been relatively
constant. In order to cure more patients, either additional financial resources
will need to be allocated to the treatment of HCV or drug costs will need to be
reduced.
PMID- 28425407
TI - Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients
Treated with Ledipasvir / Sofosbuvir Plus Ribavirin Pretransplant.
AB - INTRODUCTION: Recurrence of HCV infection in patients with chronic hepatitis C
virus (HCV) at the time of liver transplantation is nearly universal and reduces
the likelihood of graft and patient survival. MATERIALS AND METHODS: We evaluated
outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who
received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or
up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all
patients, HCV RNA was < 15 IU/mL prior to transplant. At screening, 6 patients
were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients
underwent transplant prior to completing assigned treatment, with 4 treated for <
12 weeks. The primary endpoint was posttransplant virologic response 12 weeks
after transplant (pTVR12) in patients with HCV RNA < 15 IU/mL at their last
measurement prior to transplant. RESULTS: Overall, 94% (16/17) achieved pTVR12.
All who achieved pTVR12 received at least 11 weeks of treatment. The single
patient who did not achieve pTVR12 discontinued study drug on day 21 and
underwent liver transplant the following day. The patient had HCV RNA < 15 IU/mL
at post-transplant week 2 but died 15 days post-transplant because of multi-organ
failure and septic shock. CONCLUSION: Among a small population of HCV patients
with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus
ribavirin prior to liver transplantation was maintained after transplantation,
even if treatment was stopped early. Administration of ledipasvir / sofosbuvir
plus ribavirin before liver transplant can prevent post-transplant HCV
recurrence.
PMID- 28425408
TI - Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease:
a Systematic Review and Meta-Analysis.
AB - INTRODUCTION AND AIM: Endogenous sex hormones are associated with the risk of
diabetes and metabolic syndrome. Recent studies suggested the role of these
hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic
review and meta-analysis of observational studies investigating the association
between sex hormones and NAFLD. MATERIAL AND METHODS: A comprehensive search of
the databases of the MEDLINE and EMBASE was performed from inception through
April 2016. The inclusion criterion was the observational studies that assessed
the association of serum total testosterone (TT) and sex-hormone binding globulin
(SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95%
confidence intervals (CI) comparing between subjects with and without NAFLD by
using random-effects model. RESULTS: Sixteen trials comprising 13,721 men and
5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD
(MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men
with higher TT levels had lower odds of NAFLD whereas higher TT levels increased
the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients
with NAFLD than controls and this inverse association was stronger in women than
men and higher SHBG levels were associated with reduced odds of NAFLD.
CONCLUSION: Our meta-analysis demonstrated a sex-dependent association between TT
and NAFLD. Lower TT levels are associated with men with NAFLD and inversely
associated with women with NAFLD, whereas higher SHBG levels are associated with
lower NAFLD odds in both men and women.
PMID- 28425409
TI - The Utilization of Palliative Care Services in Patients with Cirrhosis who have
been Denied Liver Transplantation: A Single Center Retrospective Review.
AB - INTRODUCTION AND AIM: Utilization of palliative care services in patients dying
of end-stage liver disease (ESLD) is understudied. We performed a retrospective
review of palliative care services among patients with ESLD unsuitable for liver
transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased
ESLD patients considered unsuitable for LT from 2007-2012 were identified.
Patients were excluded if they received a transplant, had an incomplete workup,
were lost to follow up or whose condition improved so LT was not needed. Of the
1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients
(34.4%) received an inpatient palliative care (PC) consultation and forty-one
patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%)
transitioned to comfort measures without PC consultation (median survival < 1
day). The median interval between LT denial and PC consultation or hospice was 28
days. Median survival after PC consult or hospice referral was 15 days. In
conclusion, in a single center retrospective review of ESLD patients, palliative
care services, when utilized, were for care at the very end of life. Without
consultation, aggressive interventions continued until hours before death. We
propose that ESLD patients could benefit from PC consultation at time of LT
evaluation or based on MELD scores.
PMID- 28425410
TI - Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a
Single Center.
AB - INTRODUCTION AND AIM: Liver transplantation (LT) provides durable survival for
hepatocellular carcinoma (HCC). However, there is continuing debate concerning
the impact of wait time and acceptable tumor burden on outcomes after LT. We
sought to review outcomes of LT for HCC at a single, large U.S. center, examining
the influence of wait time on post-LT outcomes. MATERIAL AND METHODS: We reviewed
LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was
updated through 8/1/ 2015. RESULTS: From 2003-2014, 978 patients were referred
for management of HCC. 376 patients were transplanted for presumed HCC within
Milan criteria, and the results of these 376 cases were analyzed. The median
diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait
time was 62 days (0 - 1815). There was no statistical difference in recurrence
free or overall survival for those with wait time of less than or greater than
180 days from diagnosis of HCC to LT. The most important predictor of long term
survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC
as well as survival were predicted by factors related to tumor biology, including
histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein
levels. Disease recurrence occurred in 13%. The overall 5-year patient survival
was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%.
CONCLUSIONS: In this large, single-center experience with long-term data, factors
of tumor biology, but not a longer wait time, were associated with recurrence
free and overall survival.
PMID- 28425411
TI - Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection
In Patients with Low Hepatitis B Viral Load.
AB - BACKGROUND: A retrospective cohort study was conducted to investigate the effect
of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (<
2000 IU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC)
after curative resection. MATERIAL AND METHODS: A total of 192 patients with low
viral load who had received curative resection of pathologically confirmed HCC
were analyzed to determine the factors affecting prognosis. The risk factors for
survival, early and late recurrence (2 years as a cut-off) were studied. RESULTS:
The median follow-up time was 38.5 months. The overall survival rates at 1-, 3-,
and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively.
The cumulative recurrence rates at 1-, 3, and 5-year after curative resection
were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels
(> 250 IU/mL) had significantly lower survival rates than those with low HBsAg
levels (HR: 1.517, 95% CI: 1.005-2.292, P = 0.047). Stratified analysis showed
that patients with high HBsAg levels had a significantly higher late recurrence
incidence than those with low HBsAg levels (HR: 2.155, 95% CI: 1.094-4.248, P =
0.026), but did not have a significantly higher risk of early recurrence
postoperatively (HR: 1.320, 95% CI: 0.837-2.082, P = 0.233). Multivariate
analysis revealed that HBsAg > 250 IU/mL was an independent risk factor
associated with late recurrence (HR: 2.109, 95% CI: 1.068-4.165, P = 0.032).
CONCLUSIONS: HBsAg > 250 IU/mL at the time of tumor resection was an independent
risk factor for late recurrence in low viral load HCC patients.
PMID- 28425412
TI - Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse
Probability of Treatment Weighted Analysis.
AB - BACKGROUND: Evidence supporting benefit of hepatocellular carcinoma (HCC)
surveillance in reducing mortality is not well-established. The effect of HCC
surveillance in reducing mortality was assessed by an inverse probability of
treatment weighting (IPTW)-based analysis controlled for inherent bias and
confounders in observational studies. MATERIAL AND METHODS: This retrospective
cohort study was conducted on 446 patients diagnosed with HCC between 2007 and
2013 at a major referral center. Surveillance was defined as having at least 1
ultrasound test within a year before HCC diagnosis. Primary outcome was survival
estimated using the Kaplan-Meier method with lead-time bias adjustment and
compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval
(CI) were computed using conventional Cox and weighted Cox proportional hazards
analysis with IPTW adjustment. RESULTS: Of the 446 patients, 103 (23.1%) were
diagnosed with HCC through surveillance. The surveillance group had more patients
with the Barcelona-Clinic Liver Cancer stage A (80.6% vs. 33.8%, P < 0.0001),
more patients eligible for potentially curative treatment (73.8% vs. 44.9%, P <
0.0001), and longer median survival (49.6 vs. 15.9 months, P < 0.0001). By
conventional multivariate Cox analysis, HR (95% CI) of surveillance was 0.63
(0.45-0.87), P = 0.005. The estimated effect of surveillance remained similar in
the IPTW-adjusted Cox analysis (HR: 0.57; 95% CI: 0.43-0.76, P < 0.001).
CONCLUSIONS: HCC surveillance by ultrasound is associated with a 37% reduction in
mortality. Even though surveillance is recommended in all guidelines, but in
practice, it is underutilized. Interventions are needed to increase surveillance
rate for improving HCC outcome.
PMID- 28425413
TI - Ursodeoxycholic Acid Therapy in Patients with Primary Biliary Cholangitis with
Limited Liver Transplantation Availability.
AB - INTRODUCTION: There is little information on survival rates of patients with
primary biliary cholangtis (PBC) in developing countries. This is particularly
true in Latin America, where the number of liver transplants performed remains
extremely low for patients with advanced liver disease who fulfill criteria for
liver transplantation. The goal of this study was to compare survival rate of
patients with PBC in developing countries who were treated with ursodeoxycholic
acid (UDCA) versus survival of patients who received other treatments (OT)
without UDCA, prescribed before the UDCA era. MATERIAL AND METHODS: A
retrospective study was performed, including records of 78 patients with PBC in
the liver unit in a third level referral hospital in Mexico City. Patients were
followed for five years from initial diagnosis until death related to liver
disease or to the end of the study. Patients received UDCA (15 mg/kg/per day) (n
= 41) or OT (n = 37) before introduction of UDCA in Mexico. RESULTS: Response to
treatment was higher in the group that received UDCA. In the five years of follow
up, survival rates were significantly higher in the UDCA group than in the OT
group. The hazard ratio of death was higher in the OT group vs. UDCA group, HR
8.78 (95% CI, 2.52-30.61); Mayo Risk Score and gender were independently
associated with the risk of death. CONCLUSIONS: The study confirms that the use
of UDCA in countries with a limited liver transplant program increases survival
in comparison to other treatments used before the introduction of UDCA.
PMID- 28425414
TI - Cholangiohydatidosis: an Infrequent Cause of Obstructive Jaundice and Acute
Cholangitis.
AB - BACKGROUND: One of the evolutionary complications of hepatic echinococcosis (HE)
is cholangiohydatidosis, a rare cause of obstructive jaundice and cholangitis.
The aim of this study was to describe the results of surgical treatment on a
group of patients with cholangiohydatidosis and secondary cholangitis in terms of
post-operative morbidity (POM). MATERIAL AND METHOD: Case series of patients
operated on for cholangiohydatidosis and cholangitis in the Department at Surgery
of the Universidad de La Frontera and the Clinica Mayor in Temuco, Chile between
2004 and 2014. The minimum follow-up time was six months. The principal outcome
variable was the development of POM. Other variables of interest were age, sex,
cyst diameter, hematocrit, leukocytes, total bilirubin, alkaline phosphatase and
transaminases, type of surgery, existence of concomitant evolutionary
complications in the cyst, length of hospital stay, need for surgical re
intervention and mortality. Descriptive statistics were calculated. RESULTS: A
total of 20 patients were studied characterized by a median age of 53 years,
50.0% female and 20.0% having two or more cysts with a mean diameter of 13.3 +/-
6.3 cm. A median hospital stay of six days and follow-up of 34 months was
recorded. POM was 30.0%, re-intervention rate was 10.0% and mortality rate was
5.0%. CONCLUSION: Cholangiohydatidosis is a rare cause of obstructive jaundice
and cholangitis associated with significant rates of POM and mortality.
PMID- 28425415
TI - Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical
Features and Predictors of Mortality.
AB - INTRODUCTION AND AIMS: Drug-induced liver injury (DILI) is rare; however, it is
one of the important causes of acute liver failure which results in significant
morbidity or mortality. MATERIAL AND METHODS: Patients with suspected DILI were
enrolled based on predefined criteria and followed up for at least 6 months or
until normalization of liver tests. Causality assessment was done by applying the
Roussel Uclaf Causality Assessment Method model. RESULTS: We collected data from
82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41
men; median age, 38 years). The most commonly implicated drugs were
antitubercular therapy (ATT) (49%), antiepileptic drugs (12%), complementary and
alternative medicine (CAM) in 10%, antiretroviral drugs (9%) and non-steroidal
anti-inflammatory drugs (6%). 8 out of 13 deaths were liver related. Also, liver
related mortality was significantly higher for ATT DILI (17.5%) vs. those without
(2.4%) (P = 0.02). There was no significant difference in overall as well as
liver related mortality in hepatocellular, cholestatic or mixed pattern of
injury. Laboratory parameters at one week after discontinuation of drug predicted
mortality better than those at the time of DILI recognition. On multivariate
logistic regression analysis, jaundice, encephalopathy, MELD (Model for end stage
liver disease) score and alkaline phosphatase at one week, independently
predicted mortality. CONCLUSION: DILI results in significant overall mortality
(15.85%). ATT, anti-epileptic drugs, CAM and antiretroviral drugs are leading
causes of DILI in India. Presence of jaundice, encephalopathy, MELD score and
alkaline phosphatase at one week are independent predictors of mortality.
PMID- 28425416
TI - GNPAT rs11558492 is not a Major Modifier of Iron Status: Study of Italian
Hemochromatosis Patients and Blood Donors.
AB - BACKGROUND AND AIM: HFE-related Hemochromatosis (HH) is characterized by marked
phenotype heterogeneity, probably due to the combined action of acquired and
genetic factors. Among them, GNPAT rs11558492 was proposed as genetic modifier of
iron status, but results are still controversial. To shed light on these
discrepancies, we genotyped 298 Italian p.C282Y homozygotes and 169 healthy
controls. MATERIAL AND METHODS: Allele and genotype frequencies were analysed and
compared with those reported in Exome Variant Server (EVS). To explore the role
of rs11558492 as a potential modifier of iron status, serum ferritin (SF), liver
iron concentration (LIC) and iron removed (IR) were studied according to allele
and genotype frequencies. In addition, the effect of the SNP on liver fibrosis
was examined comparing patients with absent/mild-moderate fibrosis to those with
severe fibrosis-cirrhosis. RESULTS: GNPAT rs11558492 minor allele (G) frequency
(MAF) was 20.3% in HFE-HH, 17.2% in controls and 20.6% in EVS database. Genotype
frequencies were 64% and 69.2% (AA), 31.2% and 27.2% (AG), 4.8% and 3.6% (GG) in
HFE-HH and controls, respectively. No significant differences were found
comparing genotype and allele frequencies even selecting subgroups of only-males
with extreme phenotypes and low alcohol intake. SF, IR and LIC levels did not
significantly differ according to rs11558492 genotypes. Also, MAF did not differ
between patients with absent/mild fibrosis and severe fibrosis/cirrhosis.
CONCLUSIONS: Our findings indicate that GNPAT rs11558492 is not a major modifier
of iron status and is not associated with liver fibrosis in HFE-HH patients.
PMID- 28425417
TI - Spontaneous Resolution of Multiple Hepatic Masses: Hepatic Inflammatory
Pseuduotumor.
PMID- 28425418
TI - Recurrent Hyperammonemia After Abernethy Malformation Type 2 Closure: a Case
Report.
AB - The Abernethy malformation is a rare congenital malformation defined by the
presence of an extrahepatic portosystemic shunt. Although most patients are
asymptomatic, clinical encephalopathy is present in 15% of cases. We present a
patient with type 2 Abernethy malformation, hyperammonemia, and encephalopathy.
Shunt closure was performed successfully using interventional angiography;
however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy
malformation can be made easily, but the ideal patient management strategy has
not yet been established. This is the first reported patient with recurrence of
hyperammonemia after interventional treatment; we discuss the therapeutic options
for Abernethy malformation.
PMID- 28425419
TI - A Rare BSEP Mutation Associated with a Mild Form of Progressive Familial
Intrahepatic Cholestasis Type 2.
AB - Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare
cholestatic disorder diagnosed in infancy or childhood that can lead to severe
hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a
deficiency of the bile salt export protein (BSEP) and accumulation of bile inside
the hepatocytes. Hepatocellular carcinoma is another condition associated with
severe forms of deletion mutations in the ABCB11 gene. Treatment options
including ursodeoxycholic acid biliary diversion have mixed outcomes and some
patients require liver transplantation. Here, we describe two siblings with an
extremely mild form of PFIC2 inherited from heterozygous parents. The elder
sibling had acute liver failure at the age of six months and both siblings had
pruritus, cholestasis, coagulopathy and fat-soluble-vitamin deficiencies in
infancy but have been asymptomatic past infancy. Genetic testing of the siblings
revealed that each were compound heterozygotes for two missense mutations of the
ABCB11 gene: p.C68Y and p.R832H. Medical treatment typical for PFIC2 has not been
necessary for either patient. This is the first report of these variants
following a mild course in two affected patients.
PMID- 28425420
TI - HbA1c Levels as a Parameter of Glycemic Control in Patients with Liver Diseases.
PMID- 28425421
TI - Reply to "HbA1c levels as a parameter of glycemic control in patients with liver
cirrhosis".
PMID- 28425422
TI - Mass mortality of eastern box turtles with upper respiratory disease following
atypical cold weather.
AB - Emerging infectious diseases cause population declines in many ectotherms, with
outbreaks frequently punctuated by periods of mass mortality. It remains unclear,
however, whether thermoregulation by ectotherms and variation in environmental
temperature is associated with mortality risk and disease progression, especially
in wild populations. Here, we examined environmental and body temperatures of
free-ranging eastern box turtles Terrapene carolina during a mass die-off
coincident with upper respiratory disease. We recorded deaths of 17 turtles that
showed clinical signs of upper respiratory disease among 76 adult turtles
encountered in Berea, Kentucky (USA), in 2014. Of the 17 mortalities, 11 occurred
approximately 14 d after mean environmental temperature dropped 2.5 SD below the
3 mo mean. Partial genomic sequencing of the major capsid protein from 1 sick
turtle identified a ranavirus isolate similar to frog virus 3. Turtles that
lacked clinical signs of disease had significantly higher body temperatures (23
degrees C) than sick turtles (21 degrees C) during the mass mortality, but sick
turtles that survived and recovered eventually warmed (measured by temperature
loggers). Finally, there was a significant negative effect of daily environmental
temperature deviation from the 3 mo mean on survival, suggesting that rapid
decreases in environmental temperature were correlated with mortality. Our
results point to a potential role for environmental temperature variation and
body temperature in disease progression and mortality risk of eastern box turtles
affected by upper respiratory disease. Given our findings, it is possible that
colder or more variable environmental temperatures and an inability to
effectively thermoregulate are associated with poorer disease outcomes in eastern
box turtles.
PMID- 28425423
TI - Pathology and molecular analysis of Hapalotrema mistroides (Digenea:
Spirorchiidae) infecting a Mediterranean loggerhead turtle Caretta caretta.
AB - Turtle blood flukes belonging to the family Spirorchiidae (Digenea) represent a
major threat for sea turtle health and are considered the most important
parasitic cause of turtle stranding and mortality worldwide. Despite the large
diversity of spirorchiid species found globally, there are only 2 records for
free-ranging Mediterranean sea turtles that date back to the late 1800s involving
just Hapalotrema mistroides Monticelli, 1896. This study describes the first
fatal confirmed case of spirorchiidiasis in a free-ranging Mediterranean
loggerhead turtle Caretta caretta (Linnaeus) and, owing to the complexities of
taxonomic identification of these parasites, provides the first molecular
characterization and phylogenetic analysis of H. mistroides from the
Mediterranean Sea. The loggerhead turtle showed cachexia and digestive disorders
associated with severe damage to the pancreas and intestinal ganglia, caused by
deposition of Hapalotrema eggs forming granulomas. Massive Hapalotrema egg emboli
in several tissues and organs and encephalitis were the most probable
contributions to the death of the turtle. The congruence between the phylogenetic
analysis of both the ITS2 and 28S rDNA resolved the Italian and USA H. mistroides
as the same species, confirming the parasite identification. The case here
described clearly indicates that the blood flukes should be considered in the
differential diagnosis of Mediterranean sea turtle diseases.
PMID- 28425424
TI - Spatial distribution of Batrachochytrium dendrobatidis in South American
caecilians.
AB - The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) is linked to
population declines in anurans and salamanders globally. To date, however, few
studies have attempted to screen Bd in live caecilians; Bd-positive caecilians
have only been reported in Africa and French Guiana. Here, we performed a
retrospective survey of museum preserved specimens to (1) describe spatial
patterns of Bd infection in Gymnophiona across South America and (2) test whether
areas of low climatic suitability for Bd in anurans predict Bd spatial
epidemiology in caecilians. We used quantitative PCR to detect Bd in preserved
caecilians collected over a 109 yr period, and performed autologistic regressions
to test the effect of bioclimatic metrics of temperature and precipitation,
vegetation density, and elevation on the likelihood of Bd occurrence. We detected
an overall Bd prevalence of 12.4%, with positive samples spanning the Uruguayan
savanna, Brazil's Atlantic Forest, and the Amazon basin. Our autologistic models
detected a strong effect of macroclimate, a weaker effect of vegetation density,
and no effect of elevation on the likelihood of Bd occurrence. Although most of
our Bd-positive records overlapped with reported areas of high climatic
suitability for the fungus in the Neotropics, many of our new Bd-positive samples
extend far into areas of poor suitability for Bd in anurans. Our results
highlight an important gap in the study of amphibian chytridiomycosis: the
potential negative impact of Bd on Neotropical caecilians and the hypothetical
role of caecilians as Bd reservoirs.
PMID- 28425425
TI - Skeletal anomalies in reared Senegalese sole Solea senegalensis juveniles: a
radiographic approach.
AB - Reared Senegalese sole Solea senegalensis Kaup show a high incidence of vertebral
anomalies; however, little is known about its skeletal anomaly profile in the
later farming phases. The purpose of this study was to provide a detailed
description and quantification of the most common skeletal anomalies in reared
Senegalese sole in the juvenile stage by means of computed radiography. A total
of 374 Senegalese sole were classified according to the external morphology of
the fish as normal or altered and then radiographed in latero-lateral and in
dorso-ventral projections. Radiographic evaluation of anomalies focused
especially on vertebral body anomalies (VBA) and vertebral column deviations
(VCD). The 2 orthogonal projections provided a more complete visualization of the
skeleton. Approximately 75% of the individuals showed at least 1 anomaly, while
VBA and/or VCD were detected in 48.9% of the specimens. Regarding external
morphology, 88% of the fish were categorized as normal, although about 72% of
these normal fish displayed abnormalities in radiographies. The most frequent
anomalies consisted of deformations of the caudal complex plates (hypurals,
parhypural and epural), preurals and caudal vertebrae. Scoliosis was the most
prevalent among VCD, affecting the caudal area in almost 15% of the individuals.
The anomaly profile at the juvenile stages showed some differences compared to
what has been reported previously in earlier stages of development. In light of
these results, further investigation into the progression of skeletal anomalies
over time and the causative factors at later stages is required.
PMID- 28425426
TI - Production of red tilapia (Oreochromis spp.) in floating cages in the Mekong
Delta, Vietnam: mortality and health management.
AB - The Mekong Delta in Vietnam is one of the most productive aquaculture regions in
the world, in which the red tilapia (Oreochromis spp.) industry is a small-scale
industry that mainly supplies local markets in the delta region. Little is known
about the frequency of mortality events and health management in this sector. We
describe red tilapia floating cage production systems in the Mekong Delta,
Vietnam, for the purposes of quantifying mortality and associated production
factors, and describing practices that may influence pathogen introduction and
spread to and from farms. In July 2014, approximately 50 red tilapia farmers from
4 provinces (201 farmers in total) were randomly selected and interviewed. Median
overall perceived mortality (PM) within a production cycle was 35%. Overall PM
was found to be affected by province (p < 0.01), age of farmers (p = 0.01),
anticipated main reason for PM in the first 2 wk (p = 0.03), most common market
for the fish (p = 0.02), and whether farmers recorded stocking information (p =
0.01). Based on the interviews, we describe and discuss processes that
potentially affect pathogen introduction and spread on these farms, such as
movements of live and dead fish, distances between farms, mechanical
transmission, and biosecurity practices such as treating fish before stocking,
using disinfectants, and sharing equipment, and harvesters' movements. This study
provides fundamental understanding of red tilapia aquaculture management in the
Mekong Delta, and describes management factors that could become important in the
event of disease outbreaks.
PMID- 28425427
TI - Tetracapsuloides bryosalmonae abundance in river water.
AB - Tetracapsuloides bryosalmonae is a myxozoan parasite of freshwater bryozoans and
salmonids, causing proliferative kidney disease in the latter. To date, detection
of the parasite has required collection of hosts and subsequent molecular or
histological examination. The release of infectious spores from both hosts offers
an opportunity to detect the parasite in water samples. We developed a novel
SYBR(r) Green quantitative real-time PCR (qPCR) assay for T. bryosalmonae in
water samples which provides an estimation of bryozoan malacospore numbers and
tested the assay in 3 rivers in southern England (UK) over a period of 5 wk. The
assay proved to be both highly sensitive and specific to the parasite, detecting
low levels of spores throughout the study period. Larger-volume samples afforded
greater detection likelihood, but did not increase the number of spores detected,
possibly as a result of low and patchy spore distributions and lack of within
site replication of large-volume samples. Based on point-measurements,
temperature was positively associated with the likelihood of detecting spores,
possibly reflecting the temperature dependence of spore shedding from bryozoan
hosts. The presence of T. bryosalmonae in water samples was predominantly
influenced by spatial (sites within rivers, amongst rivers) and temporal
(sampling dates) factors, while the latter also influenced quantification cycle
(Cq) values and spore abundance. Environmental monitoring for infectious stages
can complement traditional methods, providing faster and easier detection and
avoiding potentially prolonged searching, collecting and destructive sampling of
invertebrate and vertebrate hosts.
PMID- 28425428
TI - Innate immune response of channel catfish Ictalurus punctatus mannose-binding
lectin to channel catfish virus (CCV).
AB - The channel catfish virus (CCV) is a pathogenic herpesvirus that infects channel
catfish Ictalurus punctatus in pond aquaculture in the southeastern USA. Mannose
binding lectin (MBL), an innate immune protein, could play an important role in
the innate response of channel catfish by binding to CCV. Cell cultures of CCV
were grown in channel catfish ovary cells (CCOC). A dot-immunoblot enzyme-linked
immunosorbent assay was done to determine the binding ability of 5 mo old channel
catfish serum MBL (26.2 ug ml-1) to CCOC infected with CCV. Two separate
nitrocellulose membrane blotting techniques were done using uninfected and
infected CCOC. The uninfected CCOC decreased by 29.3 and 33.4% in their binding
of channel catfish MBL when compared with infected CCOC using the 2 membrane
procedures. The combined average binding ability of channel catfish MBL towards
infected CCOC was therefore 31.4% greater when comparing the infected and
uninfected CCOC. Normalization equation values of MBL for the 5 mo old catfish
were compared for the 2 membrane binding procedures. The 2 normalization values
were very close (142 and 150) in binding ability of MBL to the infected CCOC. The
5 mo catfish serum had twice the concentration of MBL (26.2 ug ml-1) compared to
7 mo catfish serum (13.2 ug ml-1), and the binding percentage of 5 mo serum was
2.4 times greater in infected than in uninfected cells. This demonstrates that
the binding of channel catfish serum MBL to CCV is concentration dependent and is
related to serum concentrations of MBL.
PMID- 28425429
TI - Evidence of horizontal transmission of the cancer-associated Steamer
retrotransposon among ecological cohort bivalve species.
AB - Bivalve specimens from legacy frozen tissue collections, and others freshly
obtained, were surveyed for the presence of the Steamer long terminal repeat
(LTR)-retrotransposon associated with disseminated hemic neoplasia of the soft
shelled clam Mya areneria. Of 22 species investigated using primers for the pol
region, only Atlantic M. arenaria, Atlantic and North Sea razor clams Ensis
directus, and Baltic clams Macoma balthica from the North Sea were found to
possess copies of Steamer in their genomes. Notably, close relatives like Mya
truncata and Siliqua patula did not exhibit evidence of Steamer. Amplified
Steamer sequences were uniformly identical in all M. areneria specimens, and were
highly variable across specimens of E. directus. Variation in the latter included
nucleotide polymorphisms among and within individuals as well as length variation
in 2 specimens corresponding to the deletion of a predicted stable hairpin
structure. Results implicate Atlantic razor clams as the proximal source for
horizontal transmission of Steamer among ecologically similar yet markedly
distantly related bivalves. The consequences of cross-species transmission of the
Steamer retrotransposon are unknown, and the finding of Steamer in 3 bivalve
species suggests that further spread is possible.
PMID- 28425430
TI - Dose assessment from chronic exposure to industrial NORM in iron ore processing.
AB - Radiological exposures due to naturally occurring radioactive material (NORM) can
occur during a wide range of work-related activities in the mineral processing
and chemical industries. However, evaluation of such exposures in industrial
settings remains a difficult exercise owing inter alia to the large number of
personnel, operations and plants affected; assumptions that often have to be made
concerning the actual duration and frequency of exposures; the complex chemistry
and radioactive disequilibria involved and typically, the paucity of historical
data. In our study, the challenges associated with assessing chronic exposure to
fugitive dust enriched in 210Pb and 210Po and the determination of the associated
internal dose by inhalation and ingestion are described by reference to a case
study undertaken at an iron ore sintering plant between June 2013 and July 2015.
The applicability of default dose coefficients and biokinetic models provided by
the International Commission for Radiological Protection was verified by
combining air and dust monitoring with information on the characteristics of the
aerosols and in-vitro solubility experiments. The disparity between particulate
matter 100 microns or less in diameter (PM100), particulate matter 10 microns or
less in diameter (PM10) and 210Pb/210Po activity concentrations observed over the
different monitoring campaigns and sampling locations confirmed that use
positional short-term monitoring surveys to extrapolate intake over a year was
not appropriate and could lead to unrealistic intake and dose figures. Personal
air sampling is more appropriate for estimating the dose in such situations,
though it is not always practical and may collect insufficient quantities of
material for radiochemical analysis; this is an important constraint when dealing
with low specific activity materials.
PMID- 28425431
TI - Characterization of spatial distortion in a 0.35 T MRI-guided radiotherapy
system.
AB - Spatial distortion results in image deformation that can degrade accurate
targeting and dose calculations in MRI-guided adaptive radiotherapy. The authors
present a comprehensive assessment of a 0.35 T MRI-guided radiotherapy system's
spatial distortion using two commercially-available phantoms with regularly
spaced markers. Images of the spatial integrity phantoms were acquired using five
clinical protocols on the MRI-guided radiotherapy machine with the radiotherapy
gantry positioned at various angles. Software was developed to identify and
localize all phantom markers using a template matching approach. Rotational and
translational corrections were implemented to account for imperfect phantom
alignment. Measurements were made to assess uncertainties arising from
susceptibility artifacts, image noise, and phantom construction accuracy. For a
clinical 3D imaging protocol with a 1.5 mm reconstructed slice thickness, 100% of
spheres within a 50 mm radius of isocenter had a 3D deviation of 1 mm or less. Of
the spheres within 100 mm of isocenter, 99.9% had a 3D deviation less than 1 mm.
94.8% and 100% of the spheres within 175 mm were found to be within 1 mm and 2 mm
of the expected positions in 3D respectively. Maximum 3D distortions within 50
mm, 100 mm and 175 mm of isocenter were 0.76 mm, 1.15 mm and 1.88 mm
respectively. Distortions present in images acquired using the real-time imaging
sequence were less than 1 mm for 98.1% and 95.0% of the cylinders within 50 mm
and 100 mm of isocenter. The corresponding maximum distortion in these regions
was 1.10 mm and 1.67 mm. These results may be used to inform appropriate planning
target volume (PTV) margins for 0.35 T MRI-guided radiotherapy. Observed levels
of spatial distortion should be explicitly considered when using PTV margins of 3
mm or less or in the case of targets displaced from isocenter by more than 50 mm.
PMID- 28425432
TI - Angiogenic and lymphangiogenic profiles in histological variants of papillary
thyroid carcinoma.
AB - INTRODUCTION: Papillary thyroid carcinoma (PTC) is a well-differentiated tumor
that occurs in several histological variants whose biological behaviors remain
unclear. Angiogenesis and lymphangiogenesis are critical processes that enable
tumor progression. OBJECTIVES: The aim of this study was to evaluate the
angiogenic and lymphangiogenic phenotypes of PTC, considering the differences
between histological variants. PATIENTS AND METHODS: Angiogenic and
lymphangiogenic profiles were analyzed by determining microvascular density (MVD)
and lymphatic vessel density (LVD) in 73 cases of PTC, using
immunohistochemistry. To assess the biological markers involved in blood and
lymph vessel formation, the expression of vascular endothelial growth factor
(VEGF), cyclooxygenase 2 (COX-2), and p27kip1 (p27) was determined. RESULTS: MVD
was significantly higher in patients with high-risk PTC and in those with local
extrathyroidal and vascular invasion. Positive VEGF expression was strongly
associated with high MVD and age-related tumor enlargement. The presence of lymph
vessel invasion was associated with the expression of either VEGF or COX-2. The
analysis of angiogenesis and lymphangiogenesis in different histological variants
of PTC revealed elevated LVD rather than MVD in the follicular variant of PTC (FV
PTC).Lower MVD was observed in FV-PTC relative to the classic variant of PTC (CV
PTC). The frequency of VEGF-positive tumors was higher in CV-PTC than in FV-PTC.
A significant association between COX-2 and p27 expression was observed in FV-PTC
but not in CV-PTC. CONCLUSIONS: These results suggest that VEGF, COX-2, and p27
may be important biological markers that determine the angiogenic and
lymphangiogenic potentials of PTC, particularly between the follicular and
classic variants.
PMID- 28425434
TI - Corrigendum: Coherent creation and destruction of orbital wavepackets in Si:P
with electrical and optical read-out.
PMID- 28425433
TI - Prior context in audition informs binding and shapes simple features.
AB - A perceptual phenomenon is reported, whereby prior acoustic context has a large,
rapid and long-lasting effect on a basic auditory judgement. Pairs of tones were
devised to include ambiguous transitions between frequency components, such that
listeners were equally likely to report an upward or downward 'pitch' shift
between tones. We show that presenting context tones before the ambiguous pair
almost fully determines the perceived direction of shift. The context effect
generalizes to a wide range of temporal and spectral scales, encompassing the
characteristics of most realistic auditory scenes. Magnetoencephalographic
recordings show that a relative reduction in neural responsivity is correlated to
the behavioural effect. Finally, a computational model reproduces behavioural
results, by implementing a simple constraint of continuity for binding successive
sounds in a probabilistic manner. Contextual processing, mediated by ubiquitous
neural mechanisms such as adaptation, may be crucial to track complex sound
sources over time.
PMID- 28425436
TI - Corrigendum: MHC-dependent inhibition of uterine NK cells impedes fetal growth
and decidual vascular remodeling.
PMID- 28425435
TI - FRET biosensor uncovers cAMP nano-domains at beta-adrenergic targets that dictate
precise tuning of cardiac contractility.
AB - Compartmentalized cAMP/PKA signalling is now recognized as important for
physiology and pathophysiology, yet a detailed understanding of the properties,
regulation and function of local cAMP/PKA signals is lacking. Here we present a
fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects
compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific
multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and
myofilament sites, reveals differential kinetics and amplitudes of localized cAMP
signals. This nanoscopic heterogeneity of cAMP signals is necessary to optimize
cardiac contractility upon adrenergic activation. At low adrenergic levels, and
those mimicking heart failure, differential local cAMP responses are exacerbated,
with near abolition of cAMP signalling at certain locations. This work provides
tools and fundamental mechanistic insights into subcellular adrenergic signalling
in normal and pathological cardiac function.
PMID- 28425437
TI - Are genetic polymorphisms in the renin-angiotensin-aldosterone system associated
with essential hypertension? Evidence from genome-wide association studies.
AB - In candidate gene era, dozens of single-nucleotide polymorphisms (SNPs) within
renin-angiotensin-aldosterone system (RAAS) have been reported to be
significantly associated with hypertension. However, the unbiased genome-wide
association studies (GWAS) rarely identified the SNPs within RAAS were associated
with hypertension or blood pressure (BP) traits. In order to figure out whether
genetic polymorphisms of RAAS are really associated with hypertension, we
systemically searched the GWAS Catalogue and identified all the known RAAS genes
and relevant diseases/traits. After data processing, we found that polymorphisms
within REN, AGT, ACE2, CYP11B2, ATP6AP2 and HSD11B2 were not associated with any
disease or trait. SNPs within ACE, AGTR1, AGTR2, MAS1, RENBP and NR3C2 were
associated with other diseases or traits, but showed no direct connection with
hypertension. The only SNP associated with a BP trait, systolic BP was
rs17367504. However, it is located in the intronic region of MTHFR near many
plausible candidate genes, including CLCN6, NPPA, NPPB and AGTRAP. Therefore, the
effect of RAAS polymorphisms may have been overestimated during the 'candidate
gene era'. In the time of 'precision medicine', the power of RAAS variants needs
to be reconsidered when evaluating one's susceptibility of hypertension.
PMID- 28425438
TI - Mitochondrial DNA copy number in peripheral blood cell and hypertension risk
among mining workers: a case-control study in Chinese coal miners.
AB - Alteration of mitochondrial DNA (mtDNA) copy number, which reflects oxidant
induced cell damage, has been observed in a wide range of human diseases.
However, whether it correlates with hypertension has not been elucidated. We
aimed to explore the association between mtDNA copy number and the risk of
hypertension in Chinese coal miners. A case-control study was performed with 378
hypertension patients and 325 healthy controls in a large coal mining group
located in North China. Face-to-face interviews were conducted by trained staffs
with necessary medical knowledge. The mtDNA copy number was measured by a
quantitative real-time PCR assay using DNA extracted from peripheral blood. No
significant differences in mtDNA copy number were observed between hypertension
patients and healthy controls. However, in both case and control groups, the
mtDNA copy number was statistically significantly lower in the elder population
(>=45 years old) compared with the younger subjects (<45 years old; 7.17 vs 6.64,
P=0.005 and 7.21 vs 6.84, P=0.036). A significantly higher mtDNA copy number
could be found in hypertension patients consuming alcohol regularly compared with
no alcohol consumption patients (7.09 vs 6.69); mtDNA copy number was also
positively correlated with age and alcohol consumption. Hypertension was found
significantly correlated with factors such as age, work duration, monthly family
income and drinking status. Our results suggest that the mtDNA copy number is not
associated with hypertension in coal miners.
PMID- 28425439
TI - Activation of the hypothalamic feeding centre upon visual prey detection.
AB - The visual system plays a major role in food/prey recognition in diurnal animals,
and food intake is regulated by the hypothalamus. However, whether and how visual
information about prey is conveyed to the hypothalamic feeding centre is largely
unknown. Here we perform real-time imaging of neuronal activity in freely
behaving or constrained zebrafish larvae and demonstrate that prey or prey-like
visual stimuli activate the hypothalamic feeding centre. Furthermore, we identify
prey detector neurons in the pretectal area that project to the hypothalamic
feeding centre. Ablation of the pretectum completely abolishes prey capture
behaviour and neurotoxin expression in the hypothalamic area also reduces
feeding. Taken together, these results suggest that the pretecto-hypothalamic
pathway plays a crucial role in conveying visual information to the feeding
centre. Thus, this pathway possibly converts visual food detection into feeding
motivation in zebrafish.
PMID- 28425441
TI - Methyl parathion detection in vegetables and fruits using silver@graphene
nanoribbons nanocomposite modified screen printed electrode.
AB - We have developed a sensitive electrochemical sensor for Organophosphorus
pesticide methyl parathion (MP) using silver particles supported graphene
nanoribbons (Ag@GNRs). The Ag@GNRs nanocomposite was prepared through facile wet
chemical strategy and characterized by TEM, EDX, XRD, Raman, UV-visible,
electrochemical and impedance spectroscopies. The Ag@GNRs film modified screen
printed carbon electrode (SPCE) delivers excellent electrocatalytic ability to
the reduction of MP. The Ag@GNRs/SPCE detects sub-nanomolar concentrations of MP
with excellent selectivity. The synergic effects between special electrocatalytic
ability of Ag and excellent physicochemical properties of GNRs (large surface
area, high conductivity, high area-normalized edge-plane structures and abundant
catalytic sites) make the composite highly suitable for MP sensing. Most
importantly, the method is successfully demonstrated in vegetables and fruits
which revealed its potential real-time applicability in food analysis.
PMID- 28425440
TI - The valosin-containing protein is a novel mediator of mitochondrial respiration
and cell survival in the heart in vivo.
AB - The valosin-containing protein (VCP) participates in signaling pathways essential
for cell homeostasis in multiple tissues, however, its function in the heart in
vivo remains unknown. Here we offer the first description of the expression,
function and mechanism of action of VCP in the mammalian heart in vivo in both
normal and stress conditions. By using a transgenic (TG) mouse with cardiac
specific overexpression (3.5-fold) of VCP, we demonstrate that VCP is a new and
powerful mediator of cardiac protection against cell death in vivo, as evidenced
by a 50% reduction of infarct size after ischemia/reperfusion versus wild type.
We also identify a novel role of VCP in preserving mitochondrial respiration and
in preventing the opening of mitochondrial permeability transition pore in
cardiac myocytes under stress. In particular, by genetic deletion of inducible
isoform of nitric oxide synthase (iNOS) from VCP TG mouse and by pharmacological
inhibition of iNOS in isolated cardiac myocytes, we reveal that an increase of
expression and activity of iNOS in cardiomyocytes by VCP is an essential
mechanistic link of VCP-mediated preservation of mitochondrial function. These
data together demonstrate that VCP may represent a novel therapeutic avenue for
the prevention of myocardial ischemia.
PMID- 28425442
TI - Hierarchical Decomposition for Betweenness Centrality Measure of Complex
Networks.
AB - Betweenness centrality is an indicator of a node's centrality in a network. It is
equal to the number of shortest paths from all vertices to all others that pass
through that node. Most of real-world large networks display a hierarchical
community structure, and their betweenness computation possesses rather high
complexity. Here we propose a new hierarchical decomposition approach to speed up
the betweenness computation of complex networks. The advantage of this new method
is its effective utilization of the local structural information from the
hierarchical community. The presented method can significantly speed up the
betweenness calculation. This improvement is much more evident in those networks
with numerous homogeneous communities. Furthermore, the proposed method features
a parallel structure, which is very suitable for parallel computation. Moreover,
only a small amount of additional computation is required by our method, when
small changes in the network structure are restricted to some local communities.
The effectiveness of the proposed method is validated via the examples of two
real-world power grids and one artificial network, which demonstrates that the
performance of the proposed method is superior to that of the traditional method.
PMID- 28425443
TI - Hybridization of Strength Pareto Multiobjective Optimization with Modified Cuckoo
Search Algorithm for Rectangular Array.
AB - This research proposes the various versions of modified cuckoo search (MCS)
metaheuristic algorithm deploying the strength Pareto evolutionary algorithm
(SPEA) multiobjective (MO) optimization technique in rectangular array geometry
synthesis. Precisely, the MCS algorithm is proposed by incorporating the Roulette
wheel selection operator to choose the initial host nests (individuals) that give
better results, adaptive inertia weight to control the positions exploration of
the potential best host nests (solutions), and dynamic discovery rate to manage
the fraction probability of finding the best host nests in 3-dimensional search
space. In addition, the MCS algorithm is hybridized with the particle swarm
optimization (PSO) and hill climbing (HC) stochastic techniques along with the
standard strength Pareto evolutionary algorithm (SPEA) forming the MCSPSOSPEA and
MCSHCSPEA, respectively. All the proposed MCS-based algorithms are examined to
perform MO optimization on Zitzler-Deb-Thiele's (ZDT's) test functions. Pareto
optimum trade-offs are done to generate a set of three non-dominated solutions,
which are locations, excitation amplitudes, and excitation phases of array
elements, respectively. Overall, simulations demonstrates that the proposed
MCSPSOSPEA outperforms other compatible competitors, in gaining a high antenna
directivity, small half-power beamwidth (HPBW), low average side lobe level (SLL)
suppression, and/or significant predefined nulls mitigation, simultaneously.
PMID- 28425444
TI - Model potential for the description of metal/organic interface states.
AB - We present an analytical one-dimensional model potential for the description of
electronic interface states that form at the interface between a metal surface
and flat-lying adlayers of pi-conjugated organic molecules. The model utilizes
graphene as a universal representation of these organic adlayers. It predicts the
energy position of the interface state as well as the overlap of its wave
function with the bulk metal without free fitting parameters. We show that the
energy of the interface state depends systematically on the bond distance between
the carbon backbone of the adayers and the metal. The general applicability and
robustness of the model is demonstrated by a comparison of the calculated
energies with numerous experimental results for a number of flat-lying organic
molecules on different closed-packed metal surfaces that cover a large range of
bond distances.
PMID- 28425445
TI - Scenario dependence of future changes in climate extremes under 1.5 degrees C
and 2 degrees C global warming.
AB - The 2015 Paris Agreement aims to limit global warming below 2 degrees C and
pursue efforts to even limit it to 1.5 degrees C relative to pre-industrial
levels. Decision makers need reliable information on the impacts caused by these
warming levels for climate mitigation and adaptation measures. We explore the
changes in climate extremes, which are closely tied to economic losses and
casualties, under 1.5 degrees C and 2 degrees C global warming and their
scenario dependence using three sets of ensemble global climate model
simulations. A warming of 0.5 degrees C (from 1.5 degrees C to 2 degrees C)
leads to significant increases in temperature and precipitation extremes in most
regions. However, the projected changes in climate extremes under both warming
levels highly depend on the pathways of emissions scenarios, with different
greenhouse gas (GHG)/aerosol forcing ratio and GHG levels. Moreover, there are
multifold differences in several heavily polluted regions, among the scenarios,
in the changes in precipitation extremes due to an additional 0.5 degrees C
warming from 1.5 degrees C to 2 degrees C. Our results demonstrate that the
chemical compositions of emissions scenarios, not just the total radiative
forcing and resultant warming level, must be considered when assessing the
impacts of global 1.5/2 degrees C warming.
PMID- 28425446
TI - YAP modulates TGF-beta1-induced simultaneous apoptosis and EMT through
upregulation of the EGF receptor.
AB - YAP is a transcriptional co-regulator that plays important roles in various patho
physiological processes, including the survival and death of cells. However, the
effect of YAP on apoptosis and EMT, simultaneously mediated by TGF-beta1, is not
known. In this study, we demonstrate that YAP can modulate cell fate of apoptosis
versus EMT by acting as a surviving factor. Overexpression of YAP in mouse
mammary epithelial (NMuMG) cells suppressed TGF-beta1-induced apoptosis, which
shifted the cellular response predominantly toward EMT. In contrast, knockdown of
YAP induced spontaneous apoptosis and enhanced TGF-beta1-induced apoptosis,
leading to a sharp decrease in the proportion of surviving cells that underwent
EMT. These data suggest that YAP is an essential factor for modulating cellular
responses to TGF-beta1. Further investigation showed that YAP could regulate the
expression level and activation of EGFR. Knockdown or inhibition of EGFR
abolished the suppressive effect of YAP on apoptosis, whereas activation of EGFR
by EGF significantly reduced apoptosis caused by the knockdown of YAP. The
results indicate that EGFR and its activation are critical for YAP-mediated
suppression of TGF-beta1-induced apoptosis. This study provides a new
understanding of the regulatory mechanism underlying the determination of cell
fate in response to TGF-beta1-mediated simultaneous apoptosis and EMT.
PMID- 28425448
TI - Corrigendum: Visualization of Neuregulin 1 ectodomain shedding reveals its local
processing in vitro and in vivo.
PMID- 28425447
TI - Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein
Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal
Model.
AB - : Recombinant human myelin basic protein (rhMBP) was previously produced in the
milk of transgenic cows. Differences in molecular recognition of either hMBP or
rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This
indicated differences in immunological response between rhMBP and hMBP. Here, the
activity of free and controlled release rhMBP poly(epsilon-caprolactone)
nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was
demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model.
Following optimization of nanoformulation, discrete spherical, rough-surfaced
rhMBP NPs with high entrapment efficiency and controlled release pattern were
obtained. Results indicated that rhMBP was loaded into and electrostatically
adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP
NPs before EAE-induction reduced the average behavioral score in EAE mice and
showed only mild histological alterations and preservation of myelin sheath, with
rhMBP NPs showing increased protection. Moreover, analysis of inflammatory
cytokines (IFN-gamma and IL-10) in mice brains revealed that pretreatment with
free or rhMBP NPs significantly protected against induced inflammation. IN
CONCLUSION: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii)
nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine
and iii) clinical investigations are required to demonstrate the activity of
rhMBP NPs as a therapeutic vaccine for MS.
PMID- 28425449
TI - The Impact of Treatments for Depression on the Dynamic Network Structure of
Mental States: Two Randomized Controlled Trials.
AB - Evidence is growing that vulnerability to depression may be characterized by
strong negative feedback loops between mental states. It is unknown whether such
dynamics between mental states can be altered by treatment. This study examined
whether treatment with imipramine or treatment with Mindfulness-Based Cognitive
Therapy (MBCT) reduces the connectivity within dynamic networks of mental states
in individuals with depressive symptoms. In the Imipramine trial, individuals
diagnosed with major depression were randomized to imipramine treatment or
placebo-pill treatment (n = 50). In the Mind-Maastricht trial, individuals with
residual depressive symptoms were randomized to Mindfulness-Based Cognitive
Therapy (MBCT) or to a waiting-list control condition (n = 119). Lagged
associations among mental states, as assessed with the Experience Sampling Method
(ESM), were estimated at baseline and post-intervention. The results show that
few of the dynamic network connections changed significantly over time and few of
the changes after MBCT and imipramine treatment differed significantly from the
control groups. The decrease in average node connectivity after MBCT did not
differ from the decrease observed in the waiting-list control group. Our findings
suggest that imipramine treatment and MBCT do not greatly change the dynamic
network structure of mental states, even though they do reduce depressive
symptomatology.
PMID- 28425450
TI - Toxicological and biochemical basis of synergism between the entomopathogenic
fungus Lecanicillium muscarium and the insecticide matrine against Bemisia tabaci
(Gennadius).
AB - The sweetpotato whitefly Bemisia tabaci (Gennadius) was challenged with different
combinations of matrine (insecticide) and Lecanicillium muscarium
(entomopathogenic fungus). Our results revealed a synergistic relationship
between matrine and L. muscarium on mortality and enzyme activities of B. tabaci.
To illustrate the biochemical mechanisms involved in detoxification and immune
responses of B. tabaci against both control agents, activities of different
detoxifying and antioxidant enzymes were quantified. After combined application
of matrine and L. muscarium, activities of carboxylestrease (CarE), glutathione-s
transferase (GSTs) and chitinase (CHI) decreased during the initial infection
period. Acetylcholinestrase (AChE) activities increased during the entire
experimental period, whereas those of superoxide dismutase (SOD), peroxidase
(POD) and catalase (CAT) decreased during the later infection period. The
increased mortality and suppression of enzymatic response of B. tabaci following
matrine and L. muscarium application suggests a strong synergistic effect between
both agents. The strong synergistic effect is possibly related to the disturbance
of acetylcholine balance and changes in AchE activities of the whitefly as both
matrine and L. muscarium target insect acetylcholine (Ach) receptors which in
turn effects AchE production. Therefore, our results have revealed the complex
biochemical processes involved in the synergistic action of matrine and L.
muscarium against B. tabaci.
PMID- 28425451
TI - IFNbeta Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain
Injury.
AB - Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I
interferons (IFNalpha/beta) are critical mediators of any anti-viral immune
response and IFNbeta has been implicated in the temporary control of lentiviral
infection in the brain. Here we show that transgenic mice expressing HIV-1
envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a
transient IFNbeta response and provide evidence that IFNbeta confers neuronal
protection against HIVgp120 toxicity. In cerebrocortical cell cultures,
neuroprotection by IFNbeta against gp120 toxicity is dependent on IFNalpha
receptor 1 (IFNAR1) and the beta-chemokine CCL4, as IFNAR1 deficiency and
neutralizing antibodies against CCL4, respectively, abolish the neuroprotective
effects. We find in vivo that IFNbeta mRNA is significantly increased in
HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week
intranasal IFNbeta treatment of HIVgp120tg mice starting at 3.5 months of age
increases expression of CCL4 and concomitantly protects neuronal dendrites and
pre-synaptic terminals in cortex and hippocampus from gp120-induced damage.
Moreover, in vivo and in vitro data suggests astrocytes are a major source of
IFNbeta-induced CCL4. Altogether, our results suggest exogenous IFNbeta as a
neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced
brain injury.
PMID- 28425452
TI - Estimating the irreversible pressure drop across a stenosis by quantifying
turbulence production using 4D Flow MRI.
AB - The pressure drop across a stenotic vessel is an important parameter in medicine,
providing a commonly used and intuitive metric for evaluating the severity of the
stenosis. However, non-invasive estimation of the pressure drop under
pathological conditions has remained difficult. This study demonstrates a novel
method to quantify the irreversible pressure drop across a stenosis using 4D Flow
MRI by calculating the total turbulence production of the flow. Simulation MRI
acquisitions showed that the energy lost to turbulence production can be
accurately quantified with 4D Flow MRI within a range of practical spatial
resolutions (1-3 mm; regression slope = 0.91, R2 = 0.96). The quantification of
the turbulence production was not substantially influenced by the signal-to-noise
ratio (SNR), resulting in less than 2% mean bias at SNR > 10. Pressure drop
estimation based on turbulence production robustly predicted the irreversible
pressure drop, regardless of the stenosis severity and post-stenosis dilatation
(regression slope = 0.956, R2 = 0.96). In vitro validation of the technique in a
75% stenosis channel confirmed that pressure drop prediction based on the
turbulence production agreed with the measured pressure drop (regression slope =
1.15, R2 = 0.999, Bland-Altman agreement = 0.75 +/- 3.93 mmHg).
PMID- 28425453
TI - Aptamer-mediated impairment of EGFR-integrin alphavbeta3 complex inhibits
vasculogenic mimicry and growth of triple-negative breast cancers.
AB - Current treatment options for triple-negative breast cancers (TNBCs) is limited
by the absence of well-defined biomarkers, excluding a targeted therapy. Notably,
epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of
TNBCs and is a negative prognostic factor. In clinical trials, however, existing
EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a
valid alternative to antibodies for diagnostic and therapeutic uses. Here, we
prove that, when applied to aggressive TNBC cell lines with unique stem-like
plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents
the vasculogenic mimicry (VM) capability of the cells and destroys previously
formed channels in three-dimensional culture. Notably, we found that CL4 impairs
the matrix-induced integrin alphavbeta3 interaction with EGFR and integrin
alphavbeta3-dependent cell adhesion. Consistently, the aptamer strongly inhibits
VM and tumor growth in a xenograft TNBC model. These data suggest that in TNBC
cells, EGFR may cooperate with integrin alphavbeta3 to regulate integrin binding
to extracellular ligands required for VM, and EGFR-targeting by CL4 aptamer may
counteract this event. Overall, we demonstrate a novel mechanism of action for
CL4 related with integrin alphavbeta3-EGFR interaction, that may help to develop
new oligonucleotide-based strategy addressing unmet need for TNBCs therapy.
PMID- 28425454
TI - Association of Serum Autotaxin Levels with Liver Fibrosis in Patients with
Chronic Hepatitis C.
AB - Metabolized by liver sinusoidal endothelial cells, autotaxin (ATX) is a secreted
enzyme considered to be associated with liver damage. We sought to clarify the
diagnostic ability of ATX for liver fibrosis in 593 biopsy-confirmed hepatitis C
virus (HCV)-infected patients. The diagnostic accuracy of ATX was compared with
clinical parameters and the established fibrosis biomarkers Wisteria floribunda
agglutinin-positive Mac-2-binding protein, FIB-4 index, AST-to-platelet ratio,
and Forn's index. Median ATX levels were consistently higher in female controls
and patients than in their male counterparts (P < 0.01). Serum ATX concentration
increased significantly according to liver fibrosis stage in overall and both
genders (P < 0.001). The cutoff values of ATX for prediction of fibrosis stages
>=F1, >=F2, >=F3, and F4 were 0.8, 1.1, 1.3, and 1.7 mg/L, respectively, in male
patients and 0.9, 1.7, 1.8, and 2.0 mg/L, respectively, in female patients. The
area under the receiver operating characteristic curve for ATX to diagnose
fibrosis of >=F2 (0.861) in male patients was superior to those of FIB-4 index
and Forn's index (P < 0.001), while that in female patients (0.801) was
comparable with those of the other markers. ATX therefore represents a novel non
invasive biomarker for liver fibrosis in HCV-infected patients.
PMID- 28425455
TI - The effect of hydraulic flowback and produced water on gill morphology, oxidative
stress and antioxidant response in rainbow trout (Oncorhynchus mykiss).
AB - Hydraulic fracturing fluid are complex mixtures containing high concentrations of
salts (up to 330,000 ppm), organic, and metal contaminants. However, little data
exist on the potential mechanisms of toxicity of these flowback and produced
wastewaters (FPW) on aquatic biota. Juvenile rainbow trout were exposed to either
control, FPW (2.5 or 7.5%), FPW that had been treated with activated charcoal
(AC), or a custom salt-matched control (SW; replicating only the salt content of
FPW) for 48 hours. Gill histology revealed decreases in interlamellar cell mass
(ILCM) and mean lamellar length in all treatments (FPW, AC and SW) compared to
control, indicative of hyperosmotic stress. Liver CYP1A1 activity was
significantly elevated by 7.5-fold in the FPW 7.5% treatment only, indicative of
Phase I metabolism. Superoxide dismutase activity significantly decreased in the
gills to all treatments with the lowest activity occurring in the 7.5% FPW group.
Catalase activity increased in liver with the highest values noted in fish
exposed to 7.5% FPW. No changes were observed with respect to glutathione-S
transferase, while increased lipid peroxidation was only observed in both FPW
treatments (2.5, 7.5%). These data suggest a characteristic signature of FPW
impact which may help in risk assessment and biomonitoring of FPW spills.
PMID- 28425456
TI - Salt suppresses IFNgamma inducible chemokines through the IFNgamma-JAK1-STAT1
signaling pathway in proximal tubular cells.
AB - The mechanisms of immunoactivation by salt are now becoming clearer. However,
those of immunosuppression remain unknown. Since clinical evidence indicates that
salt protects proximal tubules from injury, we investigated mechanisms
responsible for salt causing immunosuppression in proximal tubules. We focused on
cytokine-related gene expression profiles in kidneys of mice fed a high salt diet
using microarray analysis and found that both an interferon gamma (IFNgamma)
inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor,
CXCR3, were suppressed. We further revealed that a high salt concentration
suppressed IFNgamma inducible chemokines in HK2 proximal tubular cells. Finally,
we demonstrated that a high salt concentration decreased IFNGR1 expression in the
basolateral membrane of HK2 cells, leading to decreased phosphorylation of
activation sites of Janus kinase 1 (JAK1) and Signal Transducers and Activator of
Transcription 1 (STAT1), activators of chemokines. JAK inhibitor canceled the
effect of a high salt concentration on STAT1 and chemokines, indicating that the
JAK1-STAT1 signaling pathway is essential for this mechanism. In conclusion, a
high salt concentration suppresses IFNgamma-JAK1-STAT1 signaling pathways and
chemokine expressions in proximal tubules. This finding may explain how salt
ameliorates proximal tubular injury and offer a new insight into the linkage
between salt and immunity.
PMID- 28425457
TI - Strong Reduction of Thermal Conductivity and Enhanced Thermoelectric Properties
in CoSbS1-xSex Paracostibite.
AB - In order to reduce the thermal conductivity of CoSbS, a newly developed
thermoelectric semiconductor, we have aimed at intentionally induce atomic
disorder in its structure. This endeavor was guided by Density Functional
Theory(DFT) calculations which indicated that substituting sulfur with selenium
might be easily achievable experimentally because of the low formation energy of
this point defect. Thereby, CoSbS1-xSex compounds having 0 <= x <= 1 have been
synthesized by solid state reaction. Besides the expected semiconducting
paracostibite phase, we have observed the appearance of a semimetallic costibite
phase, never reported experimentally before. This cross-fertilized theoretical
and experimental approach allowed us to reduce by 50% the thermal conductivity of
paracostibite and therefore reach a maximum zT of 0.62 at 730 K. This makes this
entirely new CoSbS1-xSex alloy very attractive for further optimizations and
potential usage in thermoelectric applications.
PMID- 28425458
TI - Anatomy of terminal moraine segments and implied lake stability on Ngozumpa
Glacier, Nepal, from electrical resistivity tomography (ERT).
AB - Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common
and pose significant outburst flood hazards if the dam is breached. While moraine
subsurface structure and internal processes are likely to influence dam
stability, only few sites have so far been investigated. We conducted electrical
resistivity tomography (ERT) surveys at two sites on the terminal moraine complex
of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability.
The resistivity signature of glacier ice at the site (100-15 kOmega m) is more
consistent with values measured from cold glacier ice and while this may be
feasible, uncertainties in the data inversion introduce ambiguity to this thermal
interpretation. However, the ERT data does provide a significant improvement to
our knowledge of the subsurface characteristics at these sites, clearly showing
the presence (or absence) of glacier ice. Our interpretation is that of a highly
complex latero-terminal moraine, resulting from interaction between previous
glacier advance, recession and outburst flooding. If the base-level Spillway Lake
continues to expand to a fully formed moraine-dammed glacial lake, the
degradation of the ice core could have implications for glacial lake outburst
risk.
PMID- 28425459
TI - Complementary spin transistor using a quantum well channel.
AB - In order to utilize the spin field effect transistor in logic applications, the
development of two types of complementary transistors, which play roles of the n-
and p-type conventional charge transistors, is an essential prerequisite. In this
research, we demonstrate complementary spin transistors consisting of two types
of devices, namely parallel and antiparallel spin transistors using InAs based
quantum well channels and exchange-biased ferromagnetic electrodes. In these spin
transistors, the magnetization directions of the source and drain electrodes are
parallel or antiparallel, respectively, depending on the exchange bias field
direction. Using this scheme, we also realize a complementary logic operation
purely with spin transistors controlled by the gate voltage, without any
additional n- or p-channel transistor.
PMID- 28425460
TI - Modulation Doping of Silicon using Aluminium-induced Acceptor States in Silicon
Dioxide.
AB - All electronic, optoelectronic or photovoltaic applications of silicon depend on
controlling majority charge carriers via doping with impurity atoms. Nanoscale
silicon is omnipresent in fundamental research (quantum dots, nanowires) but also
approached in future technology nodes of the microelectronics industry. In
general, silicon nanovolumes, irrespective of their intended purpose, suffer from
effects that impede conventional doping due to fundamental physical principles
such as out-diffusion, statistics of small numbers, quantum- or dielectric
confinement. In analogy to the concept of modulation doping, originally invented
for III-V semiconductors, we demonstrate a heterostructure modulation doping
method for silicon. Our approach utilizes a specific acceptor state of aluminium
atoms in silicon dioxide to generate holes as majority carriers in adjacent
silicon. By relocating the dopants from silicon to silicon dioxide, Si nanoscale
doping problems are circumvented. In addition, the concept of aluminium-induced
acceptor states for passivating hole selective tunnelling contacts as required
for high-efficiency photovoltaics is presented and corroborated by first carrier
lifetime and tunnelling current measurements.
PMID- 28425461
TI - Real-time Crystal Growth Visualization and Quantification by Energy-Resolved
Neutron Imaging.
AB - Energy-resolved neutron imaging is investigated as a real-time diagnostic tool
for visualization and in-situ measurements of "blind" processes. This technique
is demonstrated for the Bridgman-type crystal growth enabling remote and direct
measurements of growth parameters crucial for process optimization. The location
and shape of the interface between liquid and solid phases are monitored in real
time, concurrently with the measurement of elemental distribution within the
growth volume and with the identification of structural features with a ~100 MUm
spatial resolution. Such diagnostics can substantially reduce the development
time between exploratory small scale growth of new materials and their subsequent
commercial production. This technique is widely applicable and is not limited to
crystal growth processes.
PMID- 28425462
TI - Role of chiral quantum Hall edge states in nuclear spin polarization.
AB - Resistively detected NMR (RDNMR) based on dynamic nuclear polarization (DNP) in a
quantum Hall ferromagnet (QHF) is a highly sensitive method for the discovery of
fascinating quantum Hall phases; however, the mechanism of this DNP and, in
particular, the role of quantum Hall edge states in it are unclear. Here we
demonstrate the important but previously unrecognized effect of chiral edge modes
on the nuclear spin polarization. A side-by-side comparison of the RDNMR signals
from Hall bar and Corbino disk configurations allows us to distinguish the
contributions of bulk and edge states to DNP in QHF. The unidirectional current
flow along chiral edge states makes the polarization robust to thermal
fluctuations at high temperatures and makes it possible to observe a reciprocity
principle of the RDNMR response. These findings help us better understand complex
NMR responses in QHF, which has important implications for the development of
RDNMR techniques.
PMID- 28425463
TI - Trends in the pervasiveness of type 2 diabetes, impaired fasting glucose and co
morbidities during an 8-year-follow-up of nationwide Korean population.
AB - The prevalence and incidence of type 2 diabetes, impaired fasting glucose, and co
morbidities from 2006 to 2013 in the population aged >=30 years were estimated
using the Korean NHIS database. The prevalence of type 2 diabetes increased 0.2
0.5% annually, from 5.6% in 2006 to 8% in 2013. The prevalence of type 2 diabetes
was higher in men than in women and increased with age. The incidence of type 2
diabetes was 0.81% in 2013 and was 1.4 times higher in men than in women and
increased with age. An overall decrease in the incidence rate occurred from 2006
to 2013(from 0.95 to 0.81%), which was mirrored in all age groups except the 30
39-year-old group. The prevalence of IFG was 25% in 2013. The prevalence of
hypertension(62.5 vs 16.9%) and dyslipidemia(49.5 vs 9.7%) were more prevalent in
patients with type 2 diabetes compared to non-diabetic cases. This study shows
that type 2 diabetes is both common and increasing and that one-quarter of the
Korean adult population has IFG. We also confirmed that the prevalence of
hypertension and dyslipidemia are 3.7-fold and 5.1-fold higher, respectively, in
diabetic patients than in non-diabetic adults.
PMID- 28425464
TI - Metabolic labelling of the carbohydrate core in bacterial peptidoglycan and its
applications.
AB - Bacterial cells are surrounded by a polymer known as peptidoglycan (PG), which
protects the cell from changes in osmotic pressure and small molecule insults. A
component of this material, N-acetyl-muramic acid (NAM), serves as a core
structural element for innate immune recognition of PG fragments. We report the
synthesis of modifiable NAM carbohydrate derivatives and the installation of
these building blocks into the backbone of Gram-positive and Gram-negative
bacterial PG utilizing metabolic cell wall recycling and biosynthetic
machineries. Whole cells are labelled via click chemistry and visualized using
super-resolution microscopy, revealing higher resolution PG structural details
and allowing the cell wall biosynthesis, as well as its destruction in immune
cells, to be tracked. This study will assist in the future identification of
mechanisms that the immune system uses to recognize bacteria, glean information
about fundamental cell wall architecture and aid in the design of novel
antibiotics.
PMID- 28425465
TI - Chytrid fungus infection in zebrafish demonstrates that the pathogen can
parasitize non-amphibian vertebrate hosts.
AB - Aquatic chytrid fungi threaten amphibian biodiversity worldwide owing to their
ability to rapidly expand their geographical distributions and to infect a wide
range of hosts. Combating this risk requires an understanding of chytrid host
range to identify potential reservoirs of infection and to safeguard uninfected
regions through enhanced biosecurity. Here we extend our knowledge on the host
range of the chytrid Batrachochytrium dendrobatidis by demonstrating infection of
a non-amphibian vertebrate host, the zebrafish. We observe dose-dependent
mortality and show that chytrid can infect and proliferate on zebrafish tissue.
We also show that infection phenotypes (fin erosion, cell apoptosis and muscle
degeneration) are direct symptoms of infection. Successful infection is dependent
on disrupting the zebrafish microbiome, highlighting that, as is widely found in
amphibians, commensal bacteria confer protection against this pathogen.
Collectively, our findings greatly expand the limited tool kit available to study
pathogenesis and host response to chytrid infection.
PMID- 28425466
TI - Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster
modulates DNA binding.
AB - NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes
through the progressive degradation of its [4Fe-4S] cluster on nitric oxide (NO)
exposure. We report the 1.95 A resolution crystal structure of dimeric holo
ScNsrR and show that the cluster is coordinated by the three invariant Cys
residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map
suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C
variants remain NO sensitive, DNA binding is affected. A structural comparison of
holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe-4S] cluster
stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact
with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97
from this turn, along with Arg12, which forms a salt-bridge with Asp8, are
instrumental in modulating the position of the DNA recognition helix region
relative to its major groove.
PMID- 28425467
TI - Hyperpolarized 13C Spectroscopic Evaluation of Oxidative Stress in a Rodent Model
of Steatohepatitis.
AB - Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, now
considered the most common liver disease in the western world. Approximately one
third of patients with NASH develop non-alchoholic steatohepatitis (NASH),
histologically defined by lobular and portal inflammation, and accompanied by
marked oxidative stress. Patients with NASH are at increased risk for cirrhosis
and hepatocellular carcinoma, and diagnosis currently requires invasive biopsy.
In animal models of NASH, particularly the methionine-choline deficient (MCD)
model, profound changes are seen in redox enzymes and key intracellular
antioxidants. To study antioxidant status in NASH non-invasively, we applied the
redox probe hyperpolarized [1-13C] dehydroascorbic acid (HP DHA), which is
reduced to Vitamin C (VitC) rapidly in the normal liver. In MCD mice, we observed
a significant decrease in HP DHA to VitC conversion that accompanied hepatic fat
deposition. When these animals were subsequently placed on a normal diet,
resonance ratios reverted to those seen in control mice. These findings suggest
that HP DHA, a potentially clinically translatable imaging agent, holds special
promise in imaging NASH and other metabolic syndromes, to monitor disease
progression and response to targeted therapies.
PMID- 28425468
TI - Transcriptome Analysis of Mango (Mangifera indica L.) Fruit Epidermal Peel to
Identify Putative Cuticle-Associated Genes.
AB - Mango fruit (Mangifera indica L.) are highly perishable and have a limited shelf
life, due to postharvest desiccation and senescence, which limits their global
distribution. Recent studies of tomato fruit suggest that these traits are
influenced by the expression of genes that are associated with cuticle
metabolism. However, studies of these phenomena in mango fruit are limited by the
lack of genome-scale data. In order to gain insight into the mango cuticle
biogenesis and identify putative cuticle-associated genes, we analyzed the
transcriptomes of peels from ripe and overripe mango fruit using RNA-Seq.
Approximately 400 million reads were generated and de novo assembled into 107,744
unigenes, with a mean length of 1,717 bp and with this information an online
Mango RNA-Seq Database (http://bioinfo.bti.cornell.edu/cgi-bin/mango/index.cgi)
which is a valuable genomic resource for molecular research into the biology of
mango fruit was created. RNA-Seq analysis suggested that the pathway leading to
biosynthesis of the cuticle component, cutin, is up-regulated during
overripening. This data was supported by analysis of the expression of several
putative cuticle-associated genes and by gravimetric and microscopic studies of
cuticle deposition, revealing a complex continuous pattern of cuticle deposition
during fruit development and involving substantial accumulation during
ripening/overripening.
PMID- 28425469
TI - In plastico: laboratory material newness affects growth and reproduction of
Daphnia magna reared in 50-ml polypropylene tubes.
AB - Plastic laboratory materials are found to affect vital parameters of the
waterflea Daphnia magna. The main responsible factor is defined as "newness" of
the materials. Juvenile D. magna were raised individually in; a) new laboratory
standard 50 ml polypropylene tubes, and; b) identical tubes which had been washed
and aerated for several weeks. Newness had significant effects on growth and
fecundity of D. magna. New tubes caused delayed maturation, reduced reproduction
and reduced growth when compared to washed and re-used tubes of the same
commercial brand. The findings indicate that newness of tubes has inhibiting or
toxic effects on D. magna. Often laboratory plastics are intended for single-use
due to sterility demands. Newness might be an important confounding factor in
research results and should not be disregarded. Disposable plastic utensils may
come with a seemingly ignored cost and induce adverse effects in biological test
organisms and systems. The presented findings accentuate continued need for
general awareness concerning confounding factors stemming from material
laboratory environment. Based on the present findings the authors suggest that
plastics intended for use in sensitive research may need to be washed and aerated
prior to use.
PMID- 28425470
TI - Graphene oxide as an interface phase between polyetheretherketone and
hydroxyapatite for tissue engineering scaffolds.
AB - The poor bonding strength between biopolymer and bioceramic has remained an
unsolved issue. In this study, graphene oxide (GO) was introduced as an interface
phase to improve the interfacial bonding between polyetheretherketone (PEEK) and
hydroxyapatite (HAP) for tissue engineering scaffolds. On the one hand, the
conjugated structure of GO could form strong pi-pi stacking interaction with the
benzene rings in PEEK. On the other hand, GO with a negatively charge resulting
from oxygen functional groups could adsorb the positively charged calcium atoms
(C sites) of HAP. Consequently, the dispersibility and compatibility of HAP in
the PEEK matrix increased with increasing GO content up to 1 wt%. At this time,
the compressive strength and modulus of scaffolds increased by 79.45% and 42.07%,
respectively. Furthermore, the PEEK-HAP with GO (PEEK-HAP/GO) scaffolds possessed
the ability to induce formation of bone-like apatite. And they could support
cellular adhesion, proliferation as well as osteogenic differentiation. More
importantly, in vivo bone defect repair experiments showed that new bone formed
throughout the scaffolds at 60 days after implantation. All these results
suggested that the PEEK-HAP/GO scaffolds have a promising potential for bone
tissue engineering application.
PMID- 28425471
TI - Nonspecific synaptic plasticity improves the recognition of sparse patterns
degraded by local noise.
AB - Many forms of synaptic plasticity require the local production of volatile or
rapidly diffusing substances such as nitric oxide. The nonspecific plasticity
these neuromodulators may induce at neighboring non-active synapses is thought to
be detrimental for the specificity of memory storage. We show here that memory
retrieval may benefit from this non-specific plasticity when the applied sparse
binary input patterns are degraded by local noise. Simulations of a biophysically
realistic model of a cerebellar Purkinje cell in a pattern recognition task show
that, in the absence of noise, leakage of plasticity to adjacent synapses
degrades the recognition of sparse static patterns. However, above a local noise
level of 20%, the model with nonspecific plasticity outperforms the standard,
specific model. The gain in performance is greatest when the spatial distribution
of noise in the input matches the range of diffusion-induced plasticity. Hence
non-specific plasticity may offer a benefit in noisy environments or when the
pressure to generalize is strong.
PMID- 28425472
TI - Label-free single-cell separation and imaging of cancer cells using an integrated
microfluidic system.
AB - The incidence of cancer is increasing worldwide and metastatic disease, through
the spread of circulating tumor cells (CTCs), is responsible for the majority of
the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical
information supporting therapeutic decision making, and improved methods for CTC
enumeration are asked for. Microfluidics has been extensively used for this
purpose but most methods require several post-separation processing steps
including concentration of the sample before analysis. This induces a high risk
of sample loss of the collected rare cells. Here, an integrated system is
presented that efficiently eliminates this risk by integrating label-free
separation with single cell arraying of the target cell population, enabling
direct on-chip tumor cell identification and enumeration. Prostate cancer cells
(DU145) spiked into a sample with whole blood concentration of the peripheral
blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at
a recovery of 76.2 +/- 5.9% of the cancer cells and a minute contamination of
0.12 +/- 0.04% PBMCs while simultaneously enabling a 20x volumetric
concentration. This constitutes a first step towards a fully integrated system
for rapid label-free separation and on-chip phenotypic characterization of
circulating tumor cells from peripheral venous blood in clinical practice.
PMID- 28425473
TI - 2D-DIGE as a strategy to identify serum biomarkers in Mexican patients with Type
2 diabetes with different body mass index.
AB - Obesity and type 2 diabetes(T2D) are the most prevalent and serious metabolic
diseases affecting people worldwide. However racial and ethnic disparities seems
to be a risk factor for their development. Mexico has been named as one of the
largest populations with the highest prevalence of diabetes and obesity. The aim
of this study was to identify novel T2D-associated proteins in Mexican patients.
Blood samples were collected from 62 Mexican patients with T2D and they were
grouped according to their body mass index(BMI). A panel of 10 diabetes and
obesity serum markers was determined using MAGPIX. A comparative proteomics study
was performed using two-dimensional difference in-gel electrophoresis(2D-DIGE)
followed by mass spectrometry(LC-MS/MS). We detected 113 spots differentially
accumulated, in which 64 unique proteins were identified, proteins that were
involved in metabolism pathways, molecular transport, and cellular signalling.
Four proteins(14-3-3, ApoH, ZAG, and OTO3) showing diabetes-related variation and
also changes in relation to obesity were selected for further validation by
western blotting. Our results reveal new diabetes related proteins present in the
Mexican population. These could provide additional insight into the understanding
of diabetes development in Mexican population and may also be useful candidate
biomarkers.
PMID- 28425474
TI - Invasion of Ancestral Mammals into Dim-light Environments Inferred from Adaptive
Evolution of the Phototransduction Genes.
AB - Nocturnality is a key evolutionary innovation of mammals that enables mammals to
occupy relatively empty nocturnal niches. Invasion of ancestral mammals into
nocturnality has long been inferred from the phylogenetic relationships of crown
Mammalia, which is primarily nocturnal, and crown Reptilia, which is primarily
diurnal, although molecular evidence for this is lacking. Here we used
phylogenetic analyses of the vision genes involved in the phototransduction
pathway to predict the diel activity patterns of ancestral mammals and reptiles.
Our results demonstrated that the common ancestor of the extant Mammalia was
dominated by positive selection for dim-light vision, supporting the predominate
nocturnality of the ancestral mammals. Further analyses showed that the
nocturnality of the ancestral mammals was probably derived from the predominate
diurnality of the ancestral amniotes, which featured strong positive selection
for bright-light vision. Like the ancestral amniotes, the common ancestor of the
extant reptiles and various taxa in Squamata, one of the main competitors of the
temporal niches of the ancestral mammals, were found to be predominate diurnality
as well. Despite this relatively apparent temporal niche partitioning between
ancestral mammals and the relevant reptiles, our results suggested partial
overlap of their temporal niches during crepuscular periods.
PMID- 28425475
TI - Insecticidal activity of garlic essential oil and their constituents against the
mealworm beetle, Tenebrio molitor Linnaeus (Coleoptera: Tenebrionidae).
AB - This study evaluated the insecticidal activity of garlic, Allium sativum Linnaeus
(Amaryllidaceae) essential oil and their principal constituents on Tenebrio
molitor. Garlic essential oil, diallyl disulfide, and diallyl sulfide oil were
used to compare the lethal and repellent effects on larvae, pupae and adults of
T. molitor. Six concentrations of garlic essential oil and their principal
constituents were topically applied onto larvae, pupae and adults of this insect.
Repellent effect and respiration rate of each constituent was evaluated. The
chemical composition of garlic essential oil was also determined and primary
compounds were dimethyl trisulfide (19.86%), diallyl disulfide (18.62%), diallyl
sulfide (12.67%), diallyl tetrasulfide (11.34%), and 3-vinyl-[4H]-1,2-dithiin
(10.11%). Garlic essential oil was toxic to T. molitor larva, followed by pupa
and adult. In toxic compounds, diallyl disulfide was the most toxic than diallyl
sulfide for pupa > larva > adult respectively and showing lethal effects at
different time points. Garlic essential oil, diallyl disulfide and diallyl
sulfide induced symptoms of intoxication and necrosis in larva, pupa, and adult
of T. molitor between 20-40 h after exposure. Garlic essential oil and their
compounds caused lethal and sublethal effects on T. molitor and, therefore, have
the potential for pest control.
PMID- 28425476
TI - LncRNAs2Pathways: Identifying the pathways influenced by a set of lncRNAs of
interest based on a global network propagation method.
AB - Long non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in
diverse cellular processes and biological functions. Exploring the functions
associated with lncRNAs may help provide insight into their underlying biological
mechanisms. The current methods primarily focus on investigating the functions of
individual lncRNAs; however, essential biological functions may be affected by
the combinatorial effects of multiple lncRNAs. Here, we have developed a novel
computational method, LncRNAs2Pathways, to identify the functional pathways
influenced by the combinatorial effects of a set of lncRNAs of interest based on
a global network propagation algorithm. A new Kolmogorov-Smirnov-like statistical
measure weighted by the network propagation score, which considers the expression
correlation among lncRNAs and coding genes, was used to evaluate the biological
pathways influenced by the lncRNAs of interest. We have described the
LncRNAs2Pathways methodology and illustrated its effectiveness by analyzing three
lncRNA sets associated with glioma, prostate and pancreatic cancers. We further
analyzed the reproducibility and robustness and compared our results with those
of two other methods. Based on these analyses, we showed that LncRNAs2Pathways
can effectively identify the functional pathways associated with lncRNA sets.
Finally, we implemented this method as a freely available R-based tool.
PMID- 28425477
TI - MicroRNA-27a-3p Modulates the Wnt/beta-Catenin Signaling Pathway to Promote
Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Stem Cells by
Targeting SFRP1.
AB - This study aimed to elucidate how microRNA27a-3p (miR-27a-3p) modulates the
Wnt/beta-catenin signaling pathway to promote the epithelial-mesenchymal
transition (EMT) in oral squamous carcinoma stem cells (OSCSCs) by targeting
secreted frizzled-related protein 1 (SFRP1). Flow cytometry was used to sort
OSCSCs from the SCC-9 and Tca8113 cell lines. The OSCSCs were randomly assigned
into the miR-27a-3p inhibitors group, the miR-27a-3p inhibitors-NC group, the si
SFRP1 group, the si-SFRP1 + miR-27a-3p inhibitors group and the blank group. A
luciferase reporter, immunofluorescence and Transwell assays were performed to
detect luciferase activity, SFRP1, and cell migration and invasion, respectively.
The mRNA expression of miR-27a-3p, SFRP1 and EMT markers (E-cadherin, N-cadherin,
vimentin and ZEB1) were detected using qRT-PCR. The protein expression of SFRP1,
EMT markers and the proteins of the Wnt/beta-catenin signaling pathway was
detected by Western blotting. OSCSCs showed up-regulated miR-27a-3p, Wnt/beta
catenin signaling pathway-related proteins, vimentin, N-cadherin and ZEB1 and
down-regulated SFRP1 and E-cadherin. MiR-27a-3p targeted SFRP1. Down-regulated
miR-27a-3p resulted in increased E-cadherin and SFRP1 but decreased vimentin, N
cadherin, ZEB1, the Wnt/beta-catenin signaling pathway-related proteins, and
invasive and migratory cells. Silenced SFRP1 reversed this effect. We found that
miR-27a-3p modulated the Wnt/beta-catenin signaling pathway to promote EMT in
OSCSCs by down-regulating SFRP1.
PMID- 28425478
TI - Data Intensive Genome Level Analysis for Identifying Novel, Non-Toxic Drug
Targets for Multi Drug Resistant Mycobacterium tuberculosis.
AB - We report the construction of a novel Systems Biology based virtual drug
discovery model for the prediction of non-toxic metabolic targets in
Mycobacterium tuberculosis (Mtb). This is based on a data-intensive genome level
analysis and the principle of conservation of the evolutionarily important genes.
In the 1623 sequenced Mtb strains, 890 metabolic genes identified through a
systems approach in Mtb were evaluated for non-synonymous mutations. The 33 genes
showed none or one variation in the entire 1623 strains, including 1084 Russian
MDR strains. These invariant targets were further evaluated for their
experimental and in silico essentiality as well as availability of their crystal
structure in Protein Data Bank (PDB). Along with this, targets for the common
existing antibiotics and the new Tb drug candidates were also screened for their
variation across 1623 strains of Mtb for understanding the drug resistance. We
propose that the reduced set of these reported targets could be a more effective
starting point for medicinal chemists in generating new chemical leads. This
approach has the potential of fueling the dried up Tuberculosis (Tb) drug
discovery pipeline.
PMID- 28425479
TI - Perturbed oral motor control due to anesthesia during intraoral manipulation of
food.
AB - Sensory information from periodontal mechanoreceptors (PMRs) surrounding the
roots of natural teeth is important for optimizing the positioning of food and
adjustment of force vectors during precision biting. The present experiment was
designed to test the hypothesis; that reduction of afferent inputs from the PMRs,
by anesthesia, perturbs the oral fine motor control and related jaw movements
during intraoral manipulation of morsels of food. Thirty healthy volunteers with
a natural dentition were equally divided into experimental and control groups.
The participants in both groups were asked to manipulate and split a spherical
candy into two equal halves with the front teeth. An intervention was made by
anesthetizing the upper and lower incisors of the experimental group while the
control group performed the task without intervention. Performance of the split
was evaluated and the jaw movement recorded. The experimental group demonstrated
a significant decrease in measures of performance following local anesthesia.
However, there was no significant changes in the duration or position of the jaw
during movements in the experimental and control group. In conclusion, transient
deprivation of sensory information from PMRs perturbs oral fine motor control
during intraoral manipulation of food, however, no significant alterations in
duration or positions of the jaw during movements can be observed.
PMID- 28425480
TI - Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded
AAV9-GFP for gene therapy of neurological disorders.
AB - Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the
treatment of neurodegenerative diseases. While AAVs are generally administered
systemically to newborns in preclinical studies of neurological disorders, in
adults the maturity of the blood-brain barrier (BBB) must be considered when
selecting the route of administration. Delivery of AAVs into the cerebrospinal
fluid (CSF) represents an attractive approach to target the central nervous
system (CNS) and bypass the BBB. In this study, we investigated the efficacy of
intra-CSF delivery of a single-stranded (ss) AAV9-CAG-GFP vector in adult mice
via intracisternal (iCist) or intralumbar (it-Lumb) administration. It-Lumb
ssAAV9 delivery resulted in greater diffusion throughout the entire spinal cord
and green fluorescent protein (GFP) expression mainly in the cerebellum, cortex
and olfactory bulb. By contrast, iCist delivery led to strong GFP expression
throughout the entire brain. Comparison of the transduction efficiency of ssAAV9
CAG-GFP versus ssAAV9-SYN1-GFP following it-Lumb administration revealed
widespread and specific GFP expression in neurons and motoneurons of the spinal
cord and brain when the neuron-specific synapsin 1 (SYN1) promoter was used. Our
findings demonstrate that it-Lumb ssAAV9 delivery is a safe and highly efficient
means of targeting the CNS in adult mice.
PMID- 28425481
TI - Differences in salicylic acid glucose conjugations by UGT74F1 and UGT74F2 from
Arabidopsis thaliana.
AB - Salicylic acid (SA) is a signaling molecule utilized by plants in response to
various stresses. Through conjugation with small organic molecules such as
glucose, an inactive form of SA is generated which can be transported into and
stored in plant vacuoles. In the model organism Arabidopsis thaliana, SA glucose
conjugates are formed by two homologous enzymes (UGT74F1 and UGT74F2) that
transfer glucose from UDP-glucose to SA. Despite being 77% identical and with
conserved active site residues, these enzymes catalyze the formation of different
products: UGT74F1 forms salicylic acid glucoside (SAG), while UGT74F2 forms
primarily salicylic acid glucose ester (SGE). The position of the glucose on the
aglycone determines how SA is stored, further metabolized, and contributes to a
defense response. We determined the crystal structures of the UGT74F2 wild-type
and T15S mutant enzymes, in different substrate/product complexes. On the basis
of the crystal structures and the effect on enzyme activity of mutations in the
SA binding site, we propose the catalytic mechanism of SGE and SAG formation and
that SA binds to the active site in two conformations, with each enzyme selecting
a certain binding mode of SA. Additionally, we show that two threonines are key
determinants of product specificity.
PMID- 28425482
TI - Molecular differentiation of five Cinnamomum camphora chemotypes using desorption
atmospheric pressure chemical ionization mass spectrometry of raw leaves.
AB - Five chemotypes, the isoborneol-type, camphora-type, cineole-type, linalool-type
and borneol-type of Cinnamomum camphora (L.) Presl have been identified at the
molecular level based on the multivariate analysis of mass spectral fingerprints
recorded from a total of 750 raw leaf samples (i.e., 150 leaves equally collected
for each chemotype) using desorption atmospheric pressure chemical ionization
mass spectrometry (DAPCI-MS). Both volatile and semi-volatile metabolites of the
fresh leaves of C. camphora were simultaneously detected by DAPCI-MS without any
sample pretreatment, reducing the analysis time from half a day using
conventional methods (e.g., GC-MS) down to 30 s. The pattern recognition results
obtained using principal component analysis (PCA) was cross-checked by cluster
analysis (CA), showing that the difference visualized by the DAPCI-MS spectral
fingerprints was validated with 100% accuracy. The study demonstrates that DAPCI
MS meets the challenging requirements for accurate differentiation of all the
five chemotypes of C. camphora leaves, motivating more advanced application of
DAPCI-MS in plant science and forestry studies.
PMID- 28425484
TI - Mycobacterium tuberculosis resistance prediction and lineage classification from
genome sequencing: comparison of automated analysis tools.
AB - Whole-genome sequencing (WGS) has the potential to accelerate drug-susceptibility
testing (DST) to design appropriate regimens for drug-resistant tuberculosis
(TB). Several recently developed automated software tools promise to standardize
the analysis and interpretation of WGS data. We assessed five tools (CASTB,
KvarQ, Mykrobe Predictor TB, PhyResSE, and TBProfiler) with regards to DST and
phylogenetic lineage classification, which we compared with phenotypic DST,
Sanger sequencing, and traditional typing results for a collection of 91 strains.
The lineage classifications by the tools generally only differed in the
resolution of the results. However, some strains could not be classified at all
and one strain was misclassified. The sensitivities and specificities for
isoniazid and rifampicin resistance of the tools were high, whereas the results
for ethambutol, pyrazinamide, and streptomycin resistance were more variable.
False-susceptible DST results were mainly due to missing mutations in the
resistance catalogues that the respective tools employed for data interpretation.
Notably, we also found cases of false-resistance because of the misclassification
of polymorphisms as resistance mutations. In conclusion, the performance of
current WGS analysis tools for DST is highly variable. Sustainable business
models and a shared, high-quality catalogue of resistance mutations are needed to
ensure the clinical utility of these tools.
PMID- 28425485
TI - Red light improves spermatozoa motility and does not induce oxidative DNA damage.
AB - The ability to successfully fertilize ova relies upon the swimming ability of
spermatozoa. Both in humans and in animals, sperm motility has been used as a
metric for the viability of semen samples. Recently, several studies have
examined the efficacy of low dosage red light exposure for cellular repair and
increasing sperm motility. Of prime importance to the practical application of
this technique is the absence of DNA damage caused by radiation exposure. In this
study, we examine the effect of 633 nm coherent, red laser light on sperm
motility using a novel wavelet-based algorithm that allows for direct measurement
of curvilinear velocity under red light illumination. This new algorithm gives
results comparable to the standard computer-assisted sperm analysis (CASA)
system. We then assess the safety of red light treatment of sperm by analyzing,
(1) the levels of double-strand breaks in the DNA, and (2) oxidative damage in
the sperm DNA. The results demonstrate that for the parameters used there are
insignificant differences in oxidative DNA damage as a result of irradiation.
PMID- 28425483
TI - A genome-wide association study identifies six novel risk loci for primary
biliary cholangitis.
AB - Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong
hereditary component. Here, we report a genome-wide association study that
included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with
subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls.
Our results show genome-wide association of 14 PBC risk loci including previously
identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3
(STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-kappaB) and 22q13.1 (RPL3/SYNGR1). We
also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16
as novel PBC risk loci. These new findings and histochemical studies showing
enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic
portal tracks) support a disease mechanism in which the deregulation of the IL21
signalling pathway, in addition to CD4 T-cell activation and T-cell co
stimulation are critical components in the development of PBC.
PMID- 28425486
TI - Lamin B1 is required for mature neuron-specific gene expression during olfactory
sensory neuron differentiation.
AB - B-type lamins are major constituents of the nuclear lamina in all metazoan cells,
yet have specific roles in the development of certain cell types. Although they
are speculated to regulate gene expression in developmental contexts, a direct
link between B-type lamins and developmental gene expression in an in vivo system
is currently lacking. Here, we identify lamin B1 as a key regulator of gene
expression required for the formation of functional olfactory sensory neurons. By
using targeted knockout in olfactory epithelial stem cells in adult mice, we show
that lamin B1 deficient neurons exhibit attenuated response to odour stimulation.
This deficit can be explained by decreased expression of genes involved in mature
neuron function, along with increased expression of genes atypical of the
olfactory lineage. These results support that the broadly expressed lamin B1
regulates expression of a subset of genes involved in the differentiation of a
specific cell type.
PMID- 28425487
TI - Persimmon Leaves (Diospyros kaki) Extract Protects Optic Nerve Crush-Induced
Retinal Degeneration.
AB - Retinal ganglion cell (RGC) death is part of many retinal diseases. Here, we
report that the ethanol extract of Diospyros kaki (EEDK) exhibits protective
properties against retinal degeneration, both in vitro and in vivo. Upon exposure
to cytotoxic compounds, RGC-5 cells showed approximately 40% cell viability
versus the control, while pre-treatment with EEDK markedly increased cell
viability in a concentration-dependent manner. Further studies revealed that cell
survival induced by EEDK was associated with decreased levels of apoptotic
proteins, such as poly (ADP-ribose) polymerase, p53, and cleaved caspase-3. In
addition to apoptotic pathways, we demonstrated that expression levels of
antioxidant-associated proteins, such as superoxide dismutase-1, glutathione S
transferase, and glutathione peroxidase-1, were positively modulated by EEDK. In
a partial optic nerve crush mouse model, EEDK had similar ameliorating effects on
retinal degeneration resulting from mechanical damages. Therefore, our results
suggest that EEDK may have therapeutic potential against retinal degenerative
disorders, such as glaucoma.
PMID- 28425488
TI - An Analytic Approach for Optimal Geometrical Design of GaAs Nanowires for Maximal
Light Harvesting in Photovoltaic Cells.
AB - Semiconductor nanowires(NWs) with subwavelength scale diameters have demonstrated
superior light trapping features, which unravel a new pathway for low cost and
high efficiency future generation solar cells. Unlike other published work, a
fully analytic design is for the first time proposed for optimal geometrical
parameters of vertically-aligned GaAs NW arrays for maximal energy harvesting.
Using photocurrent density as the light absorbing evaluation standard, 2 MUm
length NW arrays whose multiple diameters and periodicity are quantitatively
identified achieving the maximal value of 29.88 mA/cm2 under solar illumination.
It also turns out that our method has wide suitability for single, double and
four different diameters of NW arrays for highest photon energy harvesting. To
validate this analytical method, intensive numerical three-dimensional finite
difference time-domain simulations of the NWs' light harvesting are also carried
out. Compared with the simulation results, the predicted maximal photocurrent
densities lie within 1.5% tolerance for all cases. Along with the high accuracy,
through directly disclosing the exact geometrical dimensions of NW arrays, this
method provides an effective and efficient route for high performance
photovoltaic design.
PMID- 28425489
TI - MEIS1 variant as a determinant of autonomic imbalance in Restless Legs Syndrome.
AB - Restless Legs Syndrome (RLS) is a genetically complex neurological disorder in
which overlapping genetic risk factors may contribute to the diversity and
heterogeneity of the symptoms. The main goal of the study was to investigate,
through analysis of heart rate variability (HRV), whether in RLS patients the
MEIS1 polymorphism at risk influences the sympathovagal regulation in different
sleep stages. Sixty-four RLS patients with periodic leg movement index above 15
per hour, and 38 controls underwent one night of video-polysomnographic
recording. HRV in the frequency- and time- domains was analyzed during nighttime
sleep. All RLS patients were genotyped, and homozygotes for rs2300478 in the
MEIS1 locus were used for further analysis. Comparison of the sympathovagal
pattern of RLS patients to control subjects did not show significant differences
after adjustments for confounding factors in frequency-domain analyses, but
showed an increased variability during N2 and N3 stages in time-domain analyses
in RLS patients. Sorting of RLS patients according to MEIS1 polymorphism
reconfirmed the association between MEIS1 and PLMS, and showed a significant
increased sympathovagal balance during N3 stage in those homozygotes for the risk
allele. RLS patients should be considered differently depending on MEIS1
genotype, some being potentially at risk for cardiovascular disorders.
PMID- 28425490
TI - Urinary and Fecal Metabonomics Study of the Protective Effect of Chaihu-Shu-Gan
San on Antibiotic-Induced Gut Microbiota Dysbiosis in Rats.
AB - Accumulating evidence suggests that the gut microbiota dysbiosis and their host
metabolic phenotype alteration is an important factor in human disease
development. A traditional Chinese herbal formula, Chaihu-Shu-Gan-San (CSGS), has
been effectively used in the treatment of various gastrointestinal (GI)
disorders. The present study was carried out to investigate whether CSGS
modulates the host metabolic phenotype under the condition of gut microbiota
dysbiosis. The metabonomics studies of biochemical changes in urine and feces of
antibiotic-induced gut microbiota dysbiosis rats after treatment with CSGS were
performed using UPLC-Q-TOF/MS. Partial least squares-discriminate analysis (PLS
DA) indicated that the CSGS treatment reduced the metabolic phenotype
perturbation induced by antibiotic. In addition, there was a strong correlation
between gut microbiota genera and urinary and fecal metabolites. Moreover, the
correlation analysis and the metabolic pathway analysis (MetPA) identified that
three key metabolic pathways including glycine, serine and threonine metabolism,
nicotinate and nicotinamide metabolism, and bile acid metabolism were the most
relevant pathways involved in antibiotic-induced gut microbiota dysbiosis. These
findings provided a comprehensive understanding of the protective effects of CSGS
on the host metabolic phenotype of the gut microbiota dysbiosis rats, and further
as a new source for drug leads in gut microbiota-targeted disease management.
PMID- 28425491
TI - The neural dynamics underlying the interpersonal effects of emotional expression
on decision making.
AB - Although numerous studies explore the effects of emotion on decision-making, the
existing research has mainly focused on the influence of intrapersonal emotions,
leaving the influence of one person's emotions on another's decisions
underestimated. To specify how interpersonal emotions shape decision-making and
delineate the underlying neural dynamics involved, the present study examined
brain responses to utilitarian feedback combined with angry or happy faces in
competitive and cooperative contexts. Behavioral results showed that participants
responded slower following losses than wins when competitors express happiness
but responded faster following losses than wins when cooperators express anger.
Importantly, angry faces in competitive context reversed the differentiation
pattern of feedback-related negativity (FRN) between losses and wins and
diminished the difference between losses and wins on both P300 and theta power,
but only diminished the difference on FRN between losses and wins in cooperative
context. However, when partner displays happiness, losses versus wins elicited
larger FRN and theta power in competitive context but smaller P300 in both
contexts. These results suggest that interpersonal emotions shape decisions
during both automatic motivational salience valuation (FRN) and conscious
cognitive appraisal (P300) stages of processing, in which different emotional
expressions exert interpersonal influence through different routes.
PMID- 28425492
TI - Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern
Transgenic Mice.
AB - Angiogenesis is important for normal development as well as for tumour growth.
However, the molecular and cellular mechanisms underlying angiogenesis are not
fully understood, partly because of the lack of a good animal model for imaging.
Here, we report the generation of a novel transgenic (Tg) mouse that expresses a
bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver
kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1
expression in endothelial cells and lymphatic endothelial cells during
development and tumour growth. Importantly, bioluminescence imaging of
endothelial cells from the aortic rings of Flk1-Nano-lantern BAC Tg mice enabled
us to observe endothelial sprouting for 18 hr without any detectable
phototoxicity. Furthermore, Flk1-Nano-lantern BAC Tg mice achieved time-lapse
luminescence imaging of tumour angiogenesis in freely moving mice with implanted
tumours. Thus, this transgenic mouse line contributes a unique model to study
angiogenesis within both physiological and pathological contexts.
PMID- 28425493
TI - Characterization of Different Microbubbles in Assisting Focused Ultrasound
Induced Blood-Brain Barrier Opening.
AB - Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in
CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open
the blood-brain barrier (BBB). However, limited understanding is available
regarding the effect of different microbubbles to induce BBB opening. The aim of
this study is to characterize different MBs on their effect in FUS-induced BBB
opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS
exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic
contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as
surrogates to allow molecule-penetrated quantification, BBB-opened observation,
and MBs circulation/persistence. Cavitation activity was measured via the passive
cavitation detection (PCD) setup to correlate with the exposure level and the
histological effect. Under given and identical MB concentrations, the three MBs
induced similar and equivalent BBB-opening effects and persistence. In addition,
a treatment paradigm by adapting exposure time is proposed to compensate MB decay
to retain the persistence of BBB-opening efficiency in multiple FUS exposures.
The results potentially improve understanding of the equivalence among MBs in
focused ultrasound CNS drug delivery, and provide an effective strategy for
securing persistence in this treatment modality.
PMID- 28425494
TI - Individual size but not additional nitrogen regulates tree carbon sequestration
in a subtropical forest.
AB - Recent studies have indicated that tree carbon accumulation in subtropical
forests has been negatively affected by global change phenomena such as warming
and drought. However, the long-term effect of nitrogen addition on plant carbon
storage remains poorly understood in these regions. In this study, we conducted a
10-year field experiment examining the effect of experimental N addition on plant
growth and carbon storage in a subtropical Chinese fir forest. The N levels were
0 (control), 60, 120, and 240 kg ha-1 yr-1, and the N effects on tree carbon were
divided into stand and individual levels. The results indicated that tree carbon
storage at the stand scale was not affected by long-term N addition in the
subtropical forest. By contrast, significant impacts of different tree size
classes on carbon sequestration were found under different N treatments, which
indicated that the amount of plant carbon sequestration was significantly
enhanced with tree size class. Our findings highlight the importance of community
structure and growth characteristics in Chinese fir forests, in which individual
size but not additional N regulates tree carbon sequestration in this subtropical
forest.
PMID- 28425495
TI - The BigLEN-GPR171 Peptide Receptor System Within the Basolateral Amygdala
Regulates Anxiety-Like Behavior and Contextual Fear Conditioning.
AB - Studies show that neuropeptide-receptor systems in the basolateral amygdala (BLA)
play an important role in the pathology of anxiety and other mood disorders.
Since GPR171, a recently deorphanized receptor for the abundant neuropeptide
BigLEN, is expressed in the BLA, we investigated its role in fear and anxiety
like behaviors. To carry out these studies we identified small molecule ligands
using a homology model of GPR171 to virtually screen a library of compounds. One
of the hits, MS0021570_1, was identified as a GPR171 antagonist based on its
ability to block (i) BigLEN-mediated activation of GPR171 in heterologous cells,
(ii) BigLEN-mediated hyperpolarization of BLA pyramidal neurons, and (iii)
feeding induced by DREADD-mediated activation of BigLEN containing AgRP neurons
in the arcuate nucleus. The role of GPR171 in anxiety-like behavior or fear
conditioning was evaluated following systemic or intra-BLA administration of
MS0021570_1, as well as following lentiviral-mediated knockdown of GPR171 in the
BLA. We find that systemic administration of MS0021570_1 attenuates anxiety-like
behavior while intra-BLA administration or knockdown of GPR171 in the BLA reduces
anxiety-like behavior and fear conditioning. These results indicate that the
BigLEN-GPR171 system plays an important role in these behaviors and could be a
novel target to develop therapeutics to treat psychiatric disorders.
PMID- 28425498
TI - A New Phenomenon: Sub-Tg, Solid-State, Plasticity-Induced Bonding in Polymers.
AB - Polymer self-adhesion due to the interdiffusion of macromolecules has been an
active area of research for several decades. Here, we report a new phenomenon of
sub-Tg, solid-state, plasticity-induced bonding; where amorphous polymeric films
were bonded together in a period of time on the order of a second in the solid
state at ambient temperatures, up to 60 K below their glass transition
temperature (Tg), by subjecting them to active plastic deformation. Despite the
glassy regime, the bulk plastic deformation triggered the requisite molecular
mobility of the polymer chains, causing interpenetration across the interfaces
held in contact. Quantitative levels of adhesion and the morphologies of the
fractured interfaces validated the sub-Tg, plasticity-induced, molecular
mobilization causing bonding. No-bonding outcomes (i) during the uniaxial
compressive straining of films (a near-hydrostatic setting which strongly limits
plastic flow) and (ii) between an 'elastic' and a 'plastic' film further
established the explicit role of plastic deformation in this newly reported sub
Tg solid-state bonding.
PMID- 28425496
TI - 3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel
Monkeys in a Serotonin 2A Receptor-Dependent Manner.
AB - 3,4-Methylenedioxymethamphetamine (MDMA) increases sociality in humans and
animals. Release of serotonin (5-HT) is thought to have an important role in the
increase in social behaviors, but the mechanisms underlying these effects are
poorly understood. Despite the advantages of nonhuman primate models, no studies
have examined the mechanisms of the social effects of MDMA in nonhuman primates.
The behavior and vocalizations of four group-housed squirrel monkeys were
examined following administration of MDMA, its enantiomers, and methamphetamine.
5-HT receptor antagonists and agonists were given as drug pretreatments. Data
were analyzed using linear mixed-effects models. MDMA and its enantiomers
increased affiliative social behaviors and vocalizations, whereas methamphetamine
had only modest effects on affiliative behaviors. Pretreatment with a 5-HT2A
receptor antagonist and a 5-HT2C receptor agonist attenuated the MDMA-induced
increase in social behaviors, while a 5-HT1A receptor antagonist did not alter
affiliative vocalizations and increased MDMA-induced social contact. Nonhuman
primates show MDMA-specific increases in affiliative social behaviors following
MDMA administration, in concordance with human and rodent studies. MDMA-induced
increases in social behaviors are 5-HT2A, but not 5-HT1A, receptor dependent.
Understanding the neurochemical mechanisms mediating the prosocial effects of
MDMA could help in the development of novel therapeutics with the unique social
effects of MDMA but fewer of its limitations.
PMID- 28425499
TI - Fake news threatens a climate literate world.
PMID- 28425497
TI - Single-Dose Memantine Improves Cortical Oscillatory Response Dynamics in Patients
with Schizophrenia.
AB - Aberrant gamma-band (30-80 Hz) oscillations may underlie cognitive deficits in
schizophrenia (SZ). Gamma oscillations and their regulation by NMDA receptors can
be studied via their evoked power (gammaEP) and phase locking (gammaPL) in
response to auditory steady-state stimulation; these auditory steady-state
responses (ASSRs) may be biomarkers for target engagement and early therapeutic
effects. We previously reported that memantine, an NMDA receptor antagonist,
enhanced two biomarkers of early auditory information processing: prepulse
inhibition and mismatch negativity (MMN) in SZ patients and healthy subjects
(HS). Here, we describe memantine effects on gammaEP and gammaPL in those
subjects. SZ patients (n=18) and HS (n=14) received memantine 20 mg (p.o.) and
placebo over 2 test days in a double-blind, randomized, counterbalanced, cross
over design. The ASSR paradigm (1 ms, 85 dB clicks in 250-0.5 s trains at a
frequency of 40 Hz; 0.5 s inter-train interval) was used to assess gammaEP and
gammaPL. SZ patients had reduced gammaEP and gammaPL; memantine enhanced gammaEP
and gammaPL (p<0.025 and 0.002, respectively) in both SZ and HS. In patients,
significant correlations between age and memantine effects were detected for
gammaEP and gammaPL: greater memantine sensitivity on gammaEP and gammaPL were
present in younger SZ patients, similar to our reported findings with MMN.
Memantine acutely normalized cortical oscillatory dynamics associated with NMDA
receptor dysfunction in SZ patients. Ongoing studies will clarify whether these
acute changes predict beneficial clinical, neurocognitive and functional
outcomes. These data support the use of gamma-band ASSR as a translational end
point in pro-cognitive drug discovery and early-phase clinical trials.
PMID- 28425500
TI - Structure Shapes Dynamics and Directionality in Diverse Brain Networks:
Mathematical Principles and Empirical Confirmation in Three Species.
AB - Identifying how spatially distributed information becomes integrated in the brain
is essential to understanding higher cognitive functions. Previous computational
and empirical studies suggest a significant influence of brain network structure
on brain network function. However, there have been few analytical approaches to
explain the role of network structure in shaping regional activities and
directionality patterns. In this study, analytical methods are applied to a
coupled oscillator model implemented in inhomogeneous networks. We first derive a
mathematical principle that explains the emergence of directionality from the
underlying brain network structure. We then apply the analytical methods to the
anatomical brain networks of human, macaque, and mouse, successfully predicting
simulation and empirical electroencephalographic data. The results demonstrate
that the global directionality patterns in resting state brain networks can be
predicted solely by their unique network structures. This study forms a
foundation for a more comprehensive understanding of how neural information is
directed and integrated in complex brain networks.
PMID- 28425502
TI - Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue
Scan Simulations.
AB - VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock
system. Upon blue light activation, a covalent bond is formed between VVD residue
Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD
switching from Dark state to Light state with significant conformational
deviation. However, the mechanism of this local environment initiated global
protein conformational change remains elusive. We employed a recently developed
computational approach, rigid residue scan(RRS), to systematically probe the
impact of the internal degrees of freedom in each amino acid residue of VVD on
its overall dynamics by applying rigid body constraint on each residue in
molecular dynamics simulations. Key residues were identified with distinctive
impacts on Dark and Light states, respectively. All the simulations display wide
range of distribution on a two-dimensional(2D) plot upon structural root-mean
square deviations(RMSD) from either Dark or Light state. Clustering analysis of
the 2D RMSD distribution leads to 15 representative structures with drastically
different conformation of N-terminus, which is also a key difference between Dark
and Light states of VVD. Further principle component analyses(PCA) of RRS
simulations agree with the observation of distinctive impact from individual
residues on Dark and Light states.
PMID- 28425501
TI - Plant gum identification in historic artworks.
AB - We describe an integrated and straightforward new analytical protocol that
identifies plant gums from various sample sources including cultural heritage.
Our approach is based on the identification of saccharidic fingerprints using
mass spectrometry following controlled enzymatic hydrolysis. We developed an
enzyme cocktail suitable for plant gums of unknown composition. Distinctive MS
profiles of gums such as arabic, cherry and locust-bean gums were successfully
identified. A wide range of oligosaccharidic combinations of pentose, hexose,
deoxyhexose and hexuronic acid were accurately identified in gum arabic whereas
cherry and locust bean gums showed respectively PentxHexy and Hexn profiles.
Optimized for low sample quantities, the analytical protocol was successfully
applied to contemporary and historic samples including 'Colour Box Charles
Roberson &Co' dating 1870s and drawings from the American painter Arthur Dove
(1880-1946). This is the first time that a gum is accurately identified in a
cultural heritage sample using structural information. Furthermore, this
methodology is applicable to other domains (food, cosmetic, pharmaceutical,
biomedical).
PMID- 28425503
TI - Nerve degeneration and regeneration in the cephalopod mollusc Octopus vulgaris:
the case of the pallial nerve.
AB - Regeneration is a process that restores structure and function of tissues damaged
by injury or disease. In mammals complete regeneration is often unsuccessful,
while most of the low phyla animals can re-grow many parts of their body after
amputation. Cephalopod molluscs, and in particular Octopus vulgaris, are well
known for their capacity to regenerate their arms and other body parts, including
central and peripheral nervous system. To better understand the mechanism of
recovery following nerve injury in this species we investigated the process of
axon regrowth and nerve regeneration after complete transection of the Octopus
pallial nerves. This injury induces scar formation and activates the
proliferation of hemocytes which invade the lesion site. Hemocytes appear
involved in debris removal and seem to produce factors that foster axon re
growth. Connective tissue is involved in driving regenerating fibers in a single
direction, outlining for them a well-defined pathway. Injured axons are able to
quickly re-grow thus to restoring structure and function.
PMID- 28425504
TI - SUV39H1 Reduction Is Implicated in Abnormal Inflammation in COPD.
AB - Chronic obstructive pulmonary disease(COPD) is characterized by enhanced chronic
inflammation in the airways, lung parenchyma, and circulation. We investigated
whether SUV39H1, a histone methyltransferase, is causatively implicated in the
abnormal inflammation observed in COPD. The SUV39H1 and H3K9me3 levels were
reduced in peripheral blood mononuclear cells(PBMCs), primary human small airway
epithelial cells(HSAEpCs) and lung tissues from COPD patients, which were
correlated with poor lung function and the serum IL-8 and IL-6 levels. A specific
SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory
cytokines in normal PBMCs. Mechanistically, chaetocin reduced the SUV39H1 and
H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked
unstimulated COPD HSAEpCs and led to decreased HP-1alpha levels and increased RNA
polymerase II levels. SUV39H1 knockdown reproduced the pattern of COPD
inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3
levels and suppressed inflammation. In COPD mice, chaetocin further repressed the
SUV39H1/H3K9me3 levels and enhanced inflammation. SUV39H1 epigenetically controls
a distinct panel of pro-inflammatory cytokines. Its reduction in COPD leads to a
loss of the repressive chromatin mark H3K9me3 and confers an abnormal
inflammatory response to stimulators. SUV39H1 and its regulatory pathways are
potential therapeutic targets for COPD.
PMID- 28425505
TI - Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the
CDKN1 family of cell cycle inhibitors.
AB - Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes
patients to develop different highly vascularized cancers. pVHL targets the
hypoxia-inducible transcription factor (HIF-1alpha) for degradation, modulating
the activation of various genes involved in hypoxia response. Hypoxia plays a
relevant role in regulating cell cycle progression, inducing growth arrest in
cells exposed to prolonged oxygen deprivation. However, the exact molecular
details driving this transition are far from understood. Here, we present novel
interactions between pVHL and the cyclin-dependent kinase inhibitor family CDKN1
(p21, p27 and p57). Bioinformatics analysis, yeast two-hybrid screening and co
immunoprecipitation assays were used to predict, dissect and validate the
interactions. We found that the CDKN1 proteins share a conserved region mimicking
the HIF-1alpha motif responsible for pVHL binding. Intriguingly, a p27 site
specific mutation associated to cancer is shown to modulate this novel
interaction. Our findings suggest a new connection between the pathways
regulating hypoxia and cell cycle progression.
PMID- 28425507
TI - Recent advances in boronic acid-based optical chemosensors.
AB - Reversible covalent binding of boronic acids with polyols and Lewis bases has
facilitated the development of robust chemosensors for many biologically
important species under physiologically or environmentally relevant conditions.
This minireview covers selected examples of advances reported in this area from
2014 to 2016. While the discovery of new boron-containing binding motifs and
identification of new analytical targets have expanded the ultility of boronic
acid-based molecular recognition, unconventional sensing strategies such as
exploitation of nanoscale self-assembly, multicomponent dynamic covalent
assembly, and coupling boronate ester formation with a further chemical reaction
have led to significantly improved sensor performance, enabling real-world
applications in various areas such as cell biology and asymmetric catalysis.
PMID- 28425508
TI - Spin-state modulation of molecular FeIII complexes via inclusion in halogen
bonded supramolecular networks.
AB - The cationic complex [Fe(qsal)2]+ (Hqsal = N-(8-quinolyl)salicylaldimine) is
encapsulated in anionic halogen-bonded 1D and 2D networks derived from sym
triiodotrifluorobenzene, [(C6F3I3)Cl]- and [(C6F3I3)I]-. Structural analysis and
magnetic measurements show that the spin-state of this complex can be modulated
by its inclusion in supramolecular host frameworks.
PMID- 28425506
TI - Oncogenic activity of SOX1 in glioblastoma.
AB - Glioblastoma remains the most common and deadliest type of brain tumor and
contains a population of self-renewing, highly tumorigenic glioma stem cells
(GSCs), which contributes to tumor initiation and treatment resistance.
Developmental programs participating in tissue development and homeostasis re
emerge in GSCs, supporting the development and progression of glioblastoma. SOX1
plays an important role in neural development and neural progenitor pool
maintenance. Its impact on glioblastoma remains largely unknown. In this study,
we have found that high levels of SOX1 observed in a subset of patients correlate
with lower overall survival. At the cellular level, SOX1 expression is elevated
in patient-derived GSCs and it is also higher in oncosphere culture compared to
differentiation conditions in conventional glioblastoma cell lines. Moreover,
genetic inhibition of SOX1 in patient-derived GSCs and conventional cell lines
decreases self-renewal and proliferative capacity in vitro and tumor initiation
and growth in vivo. Contrarily, SOX1 over-expression moderately promotes self
renewal and proliferation in GSCs. These functions seem to be independent of its
activity as Wnt/beta-catenin signaling regulator. In summary, these results
identify a functional role for SOX1 in regulating glioma cell heterogeneity and
plasticity, and suggest SOX1 as a potential target in the GSC population in
glioblastoma.
PMID- 28425509
TI - A macrocyclic 'Co0' complex: the relevance of ligand non-innocence to reactivity.
AB - We present a formally zero-valent compound, [Co(Mabiq)Na(OEt2)]2 (1). The complex
was characterized by crystallographic, spectroscopic and DFT computational
methods. The electronic structure is described as a CoII-(ligand-biradical).
Compound 1 is reactive toward proton sources; CoI or CoII products result,
depending on the source of protons used. The redox non-innocence of the Mabiq
ligand, which accepts both protons and electrons, has important ramifications for
reactivity.
PMID- 28425510
TI - A universal split spinach aptamer (USSA) for nucleic acid analysis and DNA
computation.
AB - We demonstrate how a single universal spinach aptamer (USSA) probe can be used to
detect multiple (potentially any) nucleic acid sequences. USSA can be used for
cost-efficient and highly selective analysis of even folded DNA and RNA analytes,
as well as for the readout of outputs of DNA logic circuits.
PMID- 28425511
TI - Conjunctive functionalization of vinyl boronate complexes with electrophiles: a
diastereoselective three-component coupling.
AB - A method for the conjunctive functionalization of vinyl boronate complexes with
electrophiles is described. The overall process represents a three-component
coupling between a vinyl boronic ester, carbon nucleophile and an electrophile,
thus affording complex multifunctionalized products from simple starting
materials. The diastereoselectivity (syn or anti) of this process is strongly
dependent upon the nature of the electrophile.
PMID- 28425512
TI - "Colored" inorganic dopants for inducing liquid crystal chiral nematic and blue
phases: monitoring of dopant-host interaction by Raman spectroscopy.
AB - A new ruthenium complex that effectively induces chiral nematic and blue phases
upon doping with a nematic liquid crystal was developed. The red-colored dopant
exhibits strong Raman scattering in solution and nematics even at low
concentrations. Further measurements at various concentrations strongly suggested
homogeneous dispersion of the dopant in chiral nematics.
PMID- 28425513
TI - Regioselective copper-catalyzed direct arylation of benzodithiophene-S,S
tetraoxide.
AB - An efficient copper-catalyzed direct arylation reaction for the regioselective
functionalization of benzodithiophene-S,S-tetraoxide has been developed. The
method demonstrates a broad scope with isolated yields ranging from good to
excellent. Furthermore, the reaction specificity for aryl iodides over the
unreactive aryl bromides provide a opportunity to generate a new donor-acceptor
donor triad.
PMID- 28425514
TI - A Fe5C2 nanocatalyst for the preferential synthesis of ethanol via dimethyl
oxalate hydrogenation.
AB - A Fe-based catalyst exhibits extremely high selectivity (89.6%) besides excellent
catalytic activity in gas-phase dimethyl oxalate hydrogenation. The ethanol
formation occurs via hydrogenation of methyl acetate instead of ethylene glycol
over the active species Fe5C2.
PMID- 28425515
TI - The role of thermodynamic stability in the characteristics of the devitrification
front of vapour-deposited glasses of toluene.
AB - Physical vapour deposition (PVD) has settled in as an alternative method to
prepare glasses with significantly enhanced properties, providing new insights
into the understanding of glass transition. One of the striking properties of
some PVD glasses is their transformation into liquid via a heterogeneous
mechanism that initiates at surfaces/interfaces. Here, we use membrane-based fast
scanning nanocalorimetry (104 K s-1) to analyse the variables that govern the
transformation mechanism of vapour-deposited toluene glasses with different
stabilities. Thin films ranging from 20 to 250 nm were prepared at deposition
temperatures between 0.70 and 1.15 times the glass transition temperature. We
show how a propagating growth front is the initial transformation mechanism in
all the vapour deposited samples, revealing a clear tendency to faster front
velocities for less stable samples. Contrary to other glass-formers such as
indomethacin, toluene shows a one-to-one relationship between limiting fictive
temperature and front velocity. We associate this behaviour with the much simpler
molecular geometry of toluene, which would prevent the presence of strong
preferential molecular arrangements in the glass. However, the propagation
distance of the growth front before the homogenous transformation mechanism
dominates the transition is found to be dependent on the preparation conditions
rather than on the thermal stability of the glass. Understanding the link between
the growth variables and the properties of PVD glasses is crucial for finding and
developing potential applications of this type of glass.
PMID- 28425516
TI - Mechanical and vibrational characterization of amyloid-like HET-s nanosheets
based on the skewed plate theory.
AB - Pathological amyloidogenic prion proteins have a toxic effect on functional cells
in the human cerebrum because of poor degradability and the tendency to
accumulate in an uncontrolled manner under physiological conditions. HET-s, a
fungal prion protein, is known to undergo conformational variations from
fibrillar to nanosheet structures during a change from low to high pH conditions.
It has been said that this conformational change can lead to self-propagation by
nucleating on the lateral surface of singlet fibrils. Efforts have been made
toward the mechanical characterization of fibrillar amyloids, but a global
understanding of amyloid-like HET-s nanosheet structures is lacking. In this
study, we analyzed the mechanical and vibrational characteristics of the skewed
HET-s nanosheet structures that developed under neutral pH conditions by
performing various molecular dynamics simulations. By applying the skewed plate
theory to HET-s nanosheets for various length scales with numerous pores inside
the structures, we found that the skewed HET-s nanosheet structure has mechanical
properties comparable to those of previously reported biological film materials
and nanomaterials. Considering the inherent characteristics of structural
stability, our observation provides valuable and detailed structural information
on skewed amyloid-like HET-s nanosheets.
PMID- 28425517
TI - Diels-Alder reactions of graphene oxides: greatly enhanced chemical reactivity by
oxygen-containing groups.
AB - Graphene oxides (GOs) or reduced GOs (rGOs) may offer extraordinary potential for
chemical functionalization of graphene due to their unique electronic and
structural properties. By means of dispersion-corrected density functional theory
computations, we systematically investigated the Diels-Alder (DA) chemistry of
GOs. Our computations showed that the dual nature of GOs as both a diene and a
dienophile is stronger than that of pristine graphene. Interestingly, the
interior bonds of a graphene surface modified by oxygen-containing groups could
be functionalized by maleic anhydride (MA) and 2,3-dimethoxybutadiene (DMBD)
through cycloaddition reactions, and the cycloaddition products of MA and DMBD
are more favorable than the non-covalent complexes between these reagents and the
GO surface. The feasibility of covalent functionalization of GOs as a diene and a
dienophile strongly depends on the local structural environment of the oxygen
groups, including the atomic arrangement and the number of these groups
surrounding the reaction site. The exothermicities for (4+2) adducts of DMBD with
GO are far larger than those of MA, which indicates that the dienophile character
of the GO surface is stronger than its behavior as a diene.
PMID- 28425518
TI - Dynamic manipulation of the local pH within a nanopore triggered by surface
induced phase transition.
AB - Manipulating the local pH within nanoconfinement is essential in nanofluidics
technology and its applications. Since the conventional strategy utilizes the
overlapping of an electric double layer formed for charge compensation by protons
near a negatively charged pore-wall surface, pH variation within a pore is
limited to the acidic side. To achieve the variation at the alkaline side, we
developed a system comprising a hydrophobic pore-wall surface and aqueous
solution containing hydrophobic cations. Beyond a threshold cation concentration,
a nanopore is filled with the second phase where the cations are remarkably
enriched due to surface-induced phase transition (SIFT) originating from the
hydrophobic effect. It is accompanied by the enrichment of coexisting anions. We
experimentally show that pH in the second phase is much higher than in the bulk
solution. Electrochemical measurements strongly suggest that the pH value can be
increased from 4.8 to 10.7 within a 10 nm nanopore in the most significant case.
This is ascribed to the enrichment of hydroxide anions. We argue that the extent
and rate of pH variation are controlled as desired.
PMID- 28425519
TI - Electrolytic conductivity-related radiofrequency heating of aqueous suspensions
of nanoparticles for biomedicine.
AB - The development of suitable contrast agents can significantly enhance the
efficiency of modern imaging and treatment techniques, such as thermoacoustic
(TA) tomography and radio-frequency (RF) hyperthermia of cancer. Here, we examine
the heating of aqueous suspensions of silicon (Si) and gold (Au) nanoparticles
(NPs) under RF irradiation in the MHz frequency range. The heating rate of
aqueous suspensions of Si NPs exhibited non-monotonic dependency on the
electrical conductivity of the suspension. The experimental results were
explained by the mathematical model considering oscillating solvated ions as the
main source of Joule heating. These ions could be the product of the dissolution
of Si NPs or organic coating of Au NPs. Thus, the ions governed the conductivity
of the suspensions, which in turn governs both the heating rate and the near
field RF TA response. The model predicted the contrast in different tissues
taking into account both Joule heating and dielectric losses.
PMID- 28425520
TI - An innovative chemical strategy for PCR-free genetic detection of pathogens by an
integrated electrochemical biosensor.
AB - An innovative chemical strategy integrated in a miniaturized electrochemical
device was developed for sensitive detection of a pathogen genome (HBV virus)
without any amplification step. The results show a limit of detection comparable
to the standard qRT-PCR method (20 copies per reaction), paving the way to future
development of genetic PoC devices addressing automatized and low-cost molecular
diagnostics.
PMID- 28425522
TI - Red luminescence control of Eu(iii) complexes by utilizing the multi-colored
electrochromism of viologen derivatives.
AB - The electroresponsive switching of red photoluminescence based on the
electrochemical coloration of cyan-magenta-green (CMG) viologen components was
achieved by combining a luminescent Eu3+ chelate and viologen derivatives,
resulting in CMG coloration in a single cell. The cell coloration was controlled
by an electrochromic (EC) reaction, which also modulated the photoluminescence of
the Eu3+ chelate with high contrast, by transferring energy from the excited
state of the Eu3+ ion to the colored states of EC molecules. Cyclic
voltammograms, photoluminescence spectra, absorption spectra, luminescence
quantum yields, and luminescence lifetimes were measured to clarify the
differences between the luminescence quenching and energy transfer efficiencies
for each C, M, and G coloration associated with the electrochromism. Thus, the
spectral overlap between the luminescence band of the Eu3+ chelate and the
absorption band of the colored EC molecules was proven to affect the efficiency
of luminescence modulation.
PMID- 28425521
TI - Chemical genomic analysis of GPR35 signaling.
AB - GPR35, a family A orphan G protein-coupled receptor, has been implicated in
inflammatory, neurological, and cardiovascular diseases. However, not much is
known about the signaling and functions of GPR35. We performed a label-free
kinome short hairpin RNA screen and identified a putative signaling network of
GPR35 in HT-29 cells, some of which was validated using gene expression,
biochemical and cellular assays. The results showed that GPR35 induced hypoxia
inducible factor 1alpha, and was involved in synaptic transmission, sensory
perception, the immune system, and morphogenetic processes. Collectively, our
data suggest that GPR35 may play an important role in response to hypoxic stress
and be a potential target for the treatment of inflammatory, cardiovascular, and
neurological disorders.
PMID- 28425523
TI - A synthetic co-crystal prepared by cooperative single-crystal-to-single-crystal
solid-state Diels-Alder reaction.
AB - A single-crystal-to-single-crystal solid-state reaction involving the 2 : 1
charge-transfer complex of 9-bromoanthracene and bis(N-cyclobutylimino)-1,4
dithiin leads to a synthetic co-crystal composed of the Diels-Alder cycloadduct
and unreacted 9-bromoanthracene molecules. Analysis of close contacts in the
product crystal and DFT energy calculations indicate an ordered arrangement of
product and unreacted molecules due to cooperative effects during the reaction.
PMID- 28425524
TI - Excited state relaxation processes of H2-evolving Ru-Pd supramolecular
photocatalysts containing a linear or non-linear bridge: a DFT and TDDFT study.
AB - In this study, the early-time excited state relaxation processes of bimetallic Ru
Pd supramolecular photocatalysts containing a linear 2,2':5',2''-terpyridine or a
nonlinear 2,2':6',2''-terpyridine bridging ligand (BL) were investigated by
density functional theory (DFT) and time-dependent DFT (TDDFT) approaches. The
bridge based metal-to-ligand charge transfer triplet (3MLCT) state of the metal
complex containing a linear bridging ligand was calculated to be the lowest
energy triplet (T1) state which is closely related to the photocatalytic H2
production, while for that having a nonlinear bridging ligand, the T1 state is a
Ru metal-centered (MC) triplet (3MCRu) state that is short-lived and rapidly
decays to the ground electronic state (S0). Our simulation provides an
alternative explanation for the smaller interligand electron transfer (ILET) rate
in the Ru-Pd complex containing a linear bridge compared to the corresponding
monometal Ru complex. Based on the calculation, we also suggest that the
successive 3MLCT -> 3MCRu -> S0 conversion is responsible for the inefficiency of
the Ru-Pd complex containing nonlinear bridge as a photocatalyst for H2
production. This study provides theoretical insights into the key steps of the
photoinduced processes of the bimetallic H2-evolving supramolecular
photocatalyst.
PMID- 28425525
TI - Exploiting hydrogen bonding interactions to probe smaller linear and cyclic
diamines binding to G-quadruplexes: a DFT and molecular dynamics study.
AB - G-quadruplexes are formed by the association of four guanine bases through
Hoogsteen hydrogen bonding in guanine-rich sequences of DNA and exist in the
telomere as well as in promoter regions of certain oncogenes. The sequences of G
quadruplex-DNA are targets for the design of molecules that can bind and can be
developed as anti-cancer drugs. The linear and cyclic protonated diamines have
been explored to bind to G-quadruplex-DNA through hydrogen bonding interactions.
The quadruplex-DNA binders exploit pi-stacking and hydrogen bonding interactions
with the phosphate backbone of loops and grooves. In this study, linear and
cyclic protonated diamines showed remarkable binding affinity for G-tetrads using
hydrogen bonding interactions. The DFT M06-2X/6-31G(d)//B3LYP/6-31+G(d) level of
theory showed that the cyclic ee-1,2-CHDA (equatorial-equatorial form of 1,2
disubstituted cyclohexadiamine di-cation) binds to the G-tetrads very strongly
(~70.0 kcal mol-1), with a much higher binding energy than the linear protonated
diamines. The binding affinity of ligands for G-tetrads with counterions has also
been examined. The binding preference of these small ligands for G-tetrads is
higher than for DNA-duplex. The binding affinity of an intercalated acridine
based ligand (BRACO-19) for G-quadruplexes has been examined and the binding
energy is relatively lower than that for the 1,2 disubstituted cyclohexadiamine
di-cation with G-tetrads. The atoms-in-molecules (AIM) analysis reveals that the
hydrogen bonding interactions between the organic systems with G-tetrads are
primarily electrostatic in nature. The molecular dynamics simulations performed
using a classical force field (GROMACS) also supported the phosphate backbone
sites of G-quadruplex-DNA to bind to these diamines. To mimic the structural
pattern of BRACO-19, the designed inhibitor N,2-bis-2(3,4-aminocyclohexyl)
acetamide (9) examined possesses two 1,2-CHDA moieties linked through an
acetamide group. The molecular dynamics results showed that the designed molecule
9 can efficiently bind to the base-pairs and the phosphate backbone of G
quadruplex-DNA using H-bonding interactions. The binding affinity calculated for
the intercalated acridine-based drug (BRACO-19) with G-quadruplexes is weaker
compared to ee-1,2-CHDA. These ligands deliver a different binding motif
(hydrogen bonding) compared to the reported G-quadruplex binders of pi
delocalized systems and will kindle interest in examining such scaffolds to
stabilize DNA.
PMID- 28425527
TI - Synthesis of SAPO-34 nanoaggregates with the assistance of an inexpensive three
in-one non-surfactant organosilane.
AB - [3-Piperazinepropylmethyldimethoxysilane (PZPMS)] as a low-cost co-template, a
crystal growth inhibitor, and a part of the silica source was used together with
triethylamine to synthesize SAPO-34 nanoaggregates with tunable compositions.
Note that the piperazinyl group of PZPMS prompts the formation of a perfect CHA
structure by eliminating the CHA/AEI intergrowth, which ensures the excellent MTO
catalytic performance of SAPO-34 nanoaggregates.
PMID- 28425528
TI - Chemomechanical oscillations with a non-redox non-oscillatory reaction.
AB - Periodic length changes, over 20%, were sustained in a pH-responsive gel by
associating the methylene glycol-sulphite OH-producing clock-reaction with
variations of the exchange time induced between the core of the gel and a steady
chemical environment. This is the first synergistic actuator that operates beyond
acid-producing redox reactions.
PMID- 28425529
TI - Influence of cations in lithium and magnesium polysulphide solutions: dependence
of the solvent chemistry.
AB - In order to gain a deeper understanding of Li and Mg polysulphides in Li/S and
Mg/S batteries, respectively, this work investigates the impact of the two
different cations as well as the influence of the electrolyte solvents' relative
dielectric permittivity and Gutmann's donor number on the solubility and relative
stability of different Li and Mg polysulphide species. Therefore, the
disproportionation and dissociation equilibria of chemically prepared "Li2S8" and
"MgS8" solutions in DMSO, DMF, ACN, THF, DME, TEGDME, and Pyr14TFSI are
characterized by UV/Vis spectroscopy. Varying the cation and the solvent reveals
their mutual interplay in stabilizing different polysulphide species. To our
knowledge, this is the first time that chemically synthesized Mg polysulphides in
solutions are studied. The results of this work provide essential knowledge for
further development of the economically, ecologically, and also in terms of
energy density and safety, attractive Mg/S batteries.
PMID- 28425530
TI - Interfacial interactions between CoTPP molecules and MgO(100) thin films.
AB - We have investigated the interactions between cobalt(ii)-tetraphenylporphyrin
(CoTPP) molecules and MgO(100) thin films on Ag(100) by means of Synchrotron
Radiation X-Ray and Ultra-Violet Photoelectron Spectroscopy (SR-XPS and SR-UPS).
At room temperature, the CoTPP monolayer consists of two different species. A
minority of molecules exhibits a strong electronic interaction with the
substrate, whereas for the majority a similar spectroscopic signature as for
multilayer molecules is observed. Based on the lateral inhomogeneity of the
surface electronic structure, we tentatively suggest that the strongly
interacting molecules adsorb with their metal center directly above oxygen ions.
Unlike for metal substrates, where a monolayer can be prepared upon heating to
above 500 K, most of the monolayer on MgO desorbs at 550 K together with the
multilayers. This indicates either a weaker molecule-substrate bond than for most
metal surfaces or a higher activation energy barrier for dehydrogenation. The
remaining molecules are presumably MgTPP molecules, originating from a 2HTPP
impurity in CoTPP.
PMID- 28425531
TI - Iridium-catalysed asymmetric allylic alkylation of benzofuran gamma-lactones
followed by heteroaromatic Cope rearrangement: study of an unusual reaction
sequence.
AB - The iridium-catalysed asymmetric allylic alkylation of gamma-lactones produces an
all-carbon quaternary stereocentre substituted by an allyl and a benzofuran. The
resulting 1,5-hexadienes were found to be excellent substrates for an unusual
heteroaromatic Cope rearrangement. We describe here the first insight into the
synthetic outcome of this intriguing reaction sequence.
PMID- 28425532
TI - Emerging tellurium nanostructures: controllable synthesis and their applications.
AB - Tellurium (Te) is a rare element in trace amounts of about one part per billion,
comparable to that of platinum and ranked 75th in the abundance of the elements
in the earth crust. Te nanostructures, as narrow bandgap semiconductors, have
numerous potential applications in the fabrication of many modern devices. The
past decades have witnessed an explosion in new strategies for synthesizing
diverse emerging Te nanostructures with controlled compositions, sizes, shapes,
and structures. Their structure-determined nature makes functional Te
nanomaterials an attractive candidate for modern applications. This review
focuses on the synthesis and morphology control of emerging Te nanostructures and
summarizes the latest developments in the applications of Te nanostructures, such
as their use as chemical transformation templates to access a huge family of
nanowires/nanotubes, batteries, photodetectors, ion detection and removal,
element doping, piezoelectric energy harvesting, gas sensing, thermoelectric
devices and many other device applications. Various Te nanostructures with
different shapes and structures will exploit the beneficial properties associated
with their assembly process and nanofabrication. Finally, the prospects for
future applications of Te nanomaterials are summarized and highlighted.
PMID- 28425534
TI - O vacancy formation in (Pr/Gd)BaCo2O5.5 and the role of antisite defects.
AB - In search for materials for intermediate temperature solid oxide fuel cells,
(Pr/Gd)BaCo2O5.5 is investigated by first principles calculations. Antisite
defects are considered as they may modify the electronic and O diffusion
properties but are rarely studied in double perovskite oxides. Octahedrally
coordinated Co atoms are shown to realize intermediate and high spin states for
PrBaCo2O5.5 and GdBaCo2O5.5, respectively, while pyramidally coordinated Co atoms
always have high spin. It turns out that O vacancy formation is significantly
easier in PrBaCo2O5.5 than in GdBaCo2O5.5, the difference in formation energy
being hardly modified by antisite defects. While pyramidally coordinated Co atoms
are not affected, we show that the presence of antisite defects causes parts of
the octahedrally coordinated Co atoms to switch from intermediate to high spin.
PMID- 28425533
TI - Impact of lipid composition and photosensitizer hydrophobicity on the efficiency
of light-triggered liposomal release.
AB - Photo-triggerable liposomes are considered nowadays as promising drug delivery
devices due to their potential to release encapsulated drugs in a spatial and
temporal manner. In this work, we have investigated the photopermeation
efficiency of three photosensitizers (PSs), namely verteporfin, pheophorbide a
and m-THPP when incorporated into liposomes with well-defined lipid compositions
(SOPC, DOPC or SLPC). By changing the nature of phospholipids and PSs, the
illumination of the studied systems was shown to significantly alter their lipid
bilayer properties via the formation of lipid peroxides. The system efficiency
depends on the PS/phospholipid association, and the ability of the PS to
peroxidize acyl chains. Our results demonstrated the possible use of these three
clinically approved (or under investigation) PSs as potential candidates for
photo-triggerable liposome conception.
PMID- 28425536
TI - Cisplatin resistance in cell models: evaluation of metallomic and biological
predictive biomarkers to address early therapy failure.
AB - Cisplatin, one of the most extensively used metallodrugs in cancer treatment,
presents the important drawback of patient resistance. This resistance is the
consequence of different processes including those preventing the formation of
DNA adducts and/or their quick removal. Thus, a tool for the accurate detection
and quantitation of cisplatin-induced adducts might be valuable for predicting
patient resistance. To prove the validity of such an assumption, highly sensitive
plasma mass spectrometry (ICP-MS) strategies were applied to determine DNA adduct
levels and intracellular Pt concentrations. These two metal-relative parameters
were combined with an evaluation of biological responses in terms of genomic
stability (with the Comet assay) and cell cycle progression (by flow cytometry)
in four human cell lines of different origins and cisplatin sensitivities (A549,
GM04312, A2780 and A2780cis), treated with low cisplatin doses (5, 10 and 20 MUM
for 3 hours). Cell viability and apoptosis were determined as resistance
indicators. Univariate linear regression analyses indicated that quantitation of
cisplatin-induced G-G intra-strand adducts, measured 1 h after treatment, was the
best predictor for viability and apoptosis in all of the cell lines. Multivariate
linear regression analyses revealed that the prediction improved when the
intracellular Pt content or the Comet data were included in the analysis, for all
sensitive cell lines and for the A2780 and A2780cis cell lines, respectively.
Thus, a reliable cisplatin resistance predictive model, which combines the
quantitation of adducts by HPLC-ICP-MS, and their repair, with the intracellular
Pt content and induced genomic instability, might be essential to identify early
therapy failure.
PMID- 28425537
TI - Using fluorescently-labeled magnetic nanocomposites as a dual contrast agent for
optical and magnetic resonance imaging.
AB - Dual-modality imaging probes synergistically combine magnetic resonance (MR) and
fluorescence into a single nanocomposite. This promising technique affords a new
level of flexibility for molecular imaging uses in biomedical research. In this
study, we report a new strategy for the synthesis of a novel attapulgite nanorod
based atta@Fe3O4@[Ru(bpy)2(fmp)]Cl2 nanocomposite (atta@Fe3O4@Ru NC). Our
synthesized NC has both photoluminescent and magnetic properties, bright
fluorescence, as well as significant magnetic resonance. Transmission electron
microscopy, energy dispersive spectroscopy, fluorescence spectrometry, and
magnetization measurements were all used to validate its properties. In vitro
studies showed that our functionalized NC had high cellular biocompatibility and
was successfully used to label living cells through endocytosis of cells.
Moreover, a CCK8 assay showed that even high concentrations of the atta@Fe3O4@Ru
NC had low toxicity. Finally, the intravenous administration of the atta@Fe3O4@Ru
NC to a rabbit model of hepatic carcinoma resulted in a marked and negatively
enhanced T2-weighted MRI in both normal liver and tumor, which can further
enhance the visibility of the liver cancer tissue and normal liver tissue.
Collectively, these results suggest that the atta@Fe3O4@Ru NC can be used for
tumor discovery and diagnosis.
PMID- 28425538
TI - UV-induced hydrogen-atom transfer and hydrogen-atom detachment in monomeric 7
azaindole isolated in Ar and n-H2 matrices.
AB - Photochemical transformations were investigated for monomers of 7-azaindole
isolated in low-temperature Ar and normal-H2 (n-H2) matrices. The most stable N1H
tautomer was the only form of the compound populated in Ar and n-H2 matrices
before any irradiation. Upon exposure of Ar matrices to UV (lambda > 270 nm)
light, two higher-energy tautomers N7H and C3H were photoproduced. Additionally,
spectral signatures of the photogenerated 7-azaindolyl radical were also found.
All of these photoproducts were experimentally observed for the first time. So
far, the N7H tautomer had been known only as a transient species, appearing upon
relaxation of photoexcited hydrogen-bonded dimers or complexes. For 7-azaindole
isolated in an n-H2 matrix and irradiated at lambda > 270 nm, only the C3H
tautomer and the 7-azaindolyl radical were photogenerated, whereas the N7H
tautomer was not photoproduced at all. The drastic dependence of photogeneration
of the N7H form on the matrix environment (solid Ar or solid n-H2) is as a
characteristic feature of a specific class of UV-induced hydrogen-atom-transfer
processes occurring in matrix-isolated heterocycles.
PMID- 28425540
TI - Chemomechanical-force-induced folding-unfolding directly controls distinct
fluorescence dual-color switching.
AB - Folding-unfolding imparts fluorescence dual color switching, thus a novel concept
to switch fluorescence between two distinct colors while avoiding traditional
bond rupturing and bond forming in photoswitching. Because folding and unfolding
minimize the wear and tear on molecular structures, the new systems have
excellent reversibility and fatigue resistance.
PMID- 28425541
TI - Photoisomerisation and light-induced morphological switching of a polyoxometalate
azobenzene hybrid.
AB - The functionalization of a spherical Keplerate-type polyoxometalate {Mo72V30}
with a cationic azobenzene surfactant has been achieved through ionic self
assembly. The photoisomerisation reaction of this complex, which emerges in a
light-triggered aggregation-disaggregation process, has been followed by 1H NMR
spectroscopy, dynamic light scattering, absorption spectroscopy and scanning
electron microscopy analyses.
PMID- 28425542
TI - Acceptor doping in the proton conductor SrZrO3.
AB - Perovskite zirconates such as SrZrO3 exhibit improved proton solubility and
conductivity when doped with trivalent cations substituting at the Zr site. In
this work, we present a detailed study of Sc and Y dopants in SrZrO3 based on
first-principles, hybrid density-functional calculations. When substituting at
the Zr site (ScZr, YZr), both dopants give rise to a single, deep acceptor level,
where the neutral impurity forms a localized hole polaron state. The epsilon(0/-)
charge transition levels are 0.60 eV and 0.58 eV above the valence-band maximum
for ScZr and YZr, respectively. Under certain growth conditions, Sc and Y will
form self-compensating donor species by substituting at the Sr site (ScSr, YSr),
and this is detrimental to proton conductivity. Due to its larger ionic radius, Y
exhibits a greater tendency than Sc to self-compensate at the Sr site. We also
investigated the proton-dopant association. The binding energy of a proton to a
negatively charged acceptor impurity is 0.41 eV for Sc and 0.31 eV for Y,
indicating that proton transport is limited by trapping at impurity sites.
PMID- 28425543
TI - In situ nuclear magnetic resonance microimaging of live biofilms in a
microchannel.
AB - Biofilms are comprised of microbial cells and an extracellular polymeric
substance (EPS) matrix that supports interactions between community members and
with the local environment. The highly hydrated EPS matrix makes the application
of many biofilm visualization techniques difficult. Hence, to better visualize
how biofilms interact with their environment, there is a need for imaging
techniques to monitor hydrated state biofilm dynamics. We employed an in situ
dynamic approach to construct label-free images of biofilms. In situ imaging was
conducted using a vacuum compatible microfluidic reactor, SALVI (System for
Analysis at the Liquid Vacuum Interface), for biofilm growth; real-time confocal
laser scanning microscopy analysis; and nuclear magnetic resonance (NMR)
microimaging and spectroscopy. We integrated SALVI microchannel fluids and live
biofilms to demonstrate in situ measurement capabilities, including velocity
mapping, diffusion coefficient mapping, relaxometry, localized spectroscopy,
relaxation times, porosity, and two- and three-dimensional imaging within the
microchannel at high spatial resolution. We monitored organic acids adjacent to
biofilms, suggesting that kinetic rate and substrate-product yield ratio studies
are possible using the SALVI microfluidic reactor for growth characterizations.
The integration of NMR microimaging studies into the SALVI platform demonstrates
that a multimodal microfluidic platform can serve as an avenue to explore complex
biological phenomena, such as biofilm attachment to surfaces, with detailed
quantitative physical and chemical mapping. The further incorporation of other
SALVI-compatible technologies, such as liquid time-of-flight secondary ion mass
spectrometry imaging, with NMR microimaging will produce a powerful correlative
approach to monitor in situ biofilm chemistry and dynamics at different spatial
scales.
PMID- 28425544
TI - In situ template synthesis of hollow nanospheres assembled from NiCo2S4@C
ultrathin nanosheets with high electrochemical activities for lithium storage and
ORR catalysis.
AB - Transition-metal sulfide hollow nanostructures have received intensive attention
in energy-related applications due to their unique structural features and high
electrochemical activities. Here, a well-designed composite of NiCo2S4@C is
successfully fabricated using a facile in situ template removal method. The
obtained composite shows unique microstructures of hollow nanospheres (~650 nm in
diameter) assembled from ultrathin NiCo2S4@C nanosheets, in which numerous
scattered NiCo2S4 nanoparticles are embedded in ultrathin carbon nanosheets,
exhibiting mesoporous features with a high surface area of 247.25 m2 g-1. When
used as anode materials for LIBs, NiCo2S4@C hollow nanospheres exhibit a high
reversible capacity of 1592 mA h g-1 at a current density of 500 mA g-1, enhanced
cycling performance maintaining a capacity of 1178 mA h g-1 after 200 cycles, and
a remarkable rate capability. Meanwhile, the hollow nanospheres display excellent
catalytic activity as ORR catalysts with a four-electron pathway and superior
durability to that of commercial Pt/C catalysts. Their excellent lithium storage
and ORR catalysis performance can be attributed to the rational incorporation of
high-activity NiCo2S4 and ultrathin carbon nanosheets, as well as unique hollow
microstructures, which offer efficient electron/ion transport, an enhanced
electroactive material/electrolyte contact area, numerous active sites, and
excellent structural stability.
PMID- 28425545
TI - Beware of phosphate: evidence of specific dendrimer-phosphate interactions.
AB - Dendrimers are extensively studied for drug delivery and catalysis, most of which
are pH dependent. Phosphate buffer solutions (PBSs) are often used to adjust the
pH. We have found that phosphate ions become incorporated into poly(amidoamine)
(PAMAM) dendrimer molecules by forming H-bonds with tertiary nitrogens. We show
that this specific interaction between H2PO4- and HPO42- ions and generation five
PAMAM dendrimers causes a decrease in hydrodynamic size, disturbing the outcome
of the size exclusion chromatography analysis. We monitored this interaction by
1H and 31P high resolution NMR, NMR-diffusiometry, pH-potentiometry and infrared
spectroscopy. Failing to take into account this effect may lead to incorrect
conclusions and misinterpreting interactions of PAMAM dendrimers with drug
molecules and subsequently incorrect dosing. The phosphate salts of amino
terminated generation five PAMAM dendrimers are stable for years when stored in
the dark, even in dilute aqueous solutions, which has important implications for
the shelf-life of dendrimer-based drug delivery systems.
PMID- 28425548
TI - Emission behaviours of novel V- and X-shaped fluorophores in response to pH and
force stimuli.
AB - A family of novel fluorophores with V- and X-shaped skeletons is rationally
designed and prepared. Due to the extended cross pi-conjugation in the X-shaped
ones, their emission wavelengths in both solution and the solid state exhibit
considerable bathochromic shifts compared with those of the V-shaped ones. It is
found that a heavy intramolecular charge transfer (ICT) effect is the primary
element for the mechanofluorochromic (MFC) response of this family, and an
appropriate crystallinity of the sample is also indispensible for it to be MFC
active. Additionally, most fluorophores in this family are responsive to pH
stimuli and display diverse and reversible changes of emission features.
Interestingly, a V-shaped fluorophore exhibits a unique size-dependent emission
behaviour, which makes it a distinctive three-color emitter.
PMID- 28425546
TI - Variable coordination of tris(2-pyridyl)phosphine and its oxide toward M(hfac)2:
a metal-specifiable switching between the formation of mono- and bis-scorpionate
complexes.
AB - An unexpected substitution of the anionic chelating ligands at the MII centre by
a neutral tripodal ligand has been observed in the reaction of MnII, CoII, NiII
and CuII hexafluoroacetylacetonates (hfac) with tris(2-pyridyl)phosphine (Py3P)
or its oxide (Py3P = O). The nature of the metal ion in M(hfac)2 and the M/L
ratio determine the degree of substitution of hfac-anions (partial vs. total) and
therefore, the structure of the complex formed (scorpionate vs. bis-scorpionate
ones, respectively). Hence, the reaction of the ligands with [Cu(hfac)2(H2O)2] in
an equimolar ratio affords scorpionate [Cu(N,N',N''-Py3P = X)(O,O'-hfac)(O
hfac)], wherein one hfac-ligand chelates metal, while the other hfac acts as an O
monodentate one. Using the two equivalents of Py3P in this reaction leads to
[Cu(N,N',N''-Py3P)2](hfac)2, which contains a bis-scorpionate cation
[Cu(Py3P)2]2+ and two noncoordinated hfac-anions. [Co(hfac)2(H2O)2] and
[Ni(hfac)2(H2O)2], regardless of the M/L molar ratio, react with Py3P = O to give
cationic scorpionates [M(N,N',N''-Py3P = O)(O,O'-hfac)(H2O)](hfac), in which one
hfac-anion is noncoordinated. In contrast, [Mn(hfac)2(H2O)2], on interaction with
Py3P, results in the cationic complex [Mn(N,N',N''-Py3P)2][Mn(hfac)3]2 bearing a
bis-scorpionate cation [Mn(Py3P)2]2+ and two [Mn(hfac)3]2- counterions. The
synthesized scorpionates have been characterized by X-ray diffractometry, cyclic
voltammetry, SQUID magnetometry, FT-IR and UV-Vis techniques.
PMID- 28425549
TI - Nicotinamide adenine dinucleotide detection based on silver nanoclusters
stabilized by a dumbbell-shaped probe.
AB - We have developed a novel method for detecting nicotinamide adenine dinucleotide
(NAD+) based on fluorescent silver nanoclusters (AgNCs) stabilized by a dumbbell
shaped DNA template containing two cytosine-loops joined in a dsDNA stem. The
design involves two types of components: a dumbbell-shaped DNA template and three
enzymes. In the presence of NAD+ as a cofactor, Escherichia coli DNA ligase
(E.coli DNA ligase) catalyzes template ligation to generate a sealed (no terminal
nucleotides) dumbbell-shaped structure, preventing digestion by exonuclease III
(Exo III) and exonuclease I (Exo I). The loop regions of the intact template
serve as sites for the deposition of highly fluorescent AgNCs. In the absence of
NAD+, the ligation reaction does not occur, and the unsealed dumbbell-shaped
template is digested into mononucleotides via cooperation of Exo III and Exo I.
The destruction of the DNA template results in the agglomeration of AgNCs into
silver nanoparticles with low fluorescence. The fluorescence enhancement depends
on the ligation and digestion of the DNA template, allowing quantitative
detection of NAD+ in the range of 0.5 nM-5000 nM with a detection limit of ~0.25
nM.
PMID- 28425550
TI - Site-selective carbon-carbon bond formation in unprotected monosaccharides using
photoredox catalysis.
AB - Site-selective photoredox reactions with somophiles readily enable branching of
the carbon skeleton of unprotected glucosides, allosides, and xylosides
regioselectively at C3. These reactions open the possibility of selective C-C
bond formation in monosaccharides without multi-step protection-deprotection
strategies.
PMID- 28425551
TI - Synthesis and characterization of a dipyriamethyrin-uranyl complex.
AB - The reaction between non-aqueous uranyl silylamide (UO2[N(SiMe3)2]2.2THF) under
anaerobic conditions or uranyl acetate (UO2(OAc)2.2H2O) under standard laboratory
conditions and dipyriamethryin affords a bench-stable uranyl complex. Competition
studies as well as DFT calculations provide support for the observed selectivity
for the uranyl cation over trivalent lanthanide and multiple transition metal
precursors.
PMID- 28425552
TI - The effect of chemical ordering and lattice mismatch on structural transitions in
phase segregating nanoalloys.
AB - We elucidate the effect of lattice mismatch and chemical ordering on structural
transitions in bimetallic nanoalloys of ~1.5 nm. We show that collective screw
dislocation motions happen in small mismatch shell@core systems while strongly
mismatched ones favour incomplete outer shell rearrangements. Cooperative
transitions can also become hindered when the chemical ordering breaks the
geometrical symmetry. Escaping from an unfavourable morphological basin occurs
first via re-arrangements of the geometry and then changes towards a better
chemical pattern. We observe that the chemical re-ordering mechanisms are
independent of system composition and stoichiometry but hinge on the initial and
final chemical arrangements.
PMID- 28425553
TI - Structural control of side-chain chromophores to achieve highly efficient electro
optic activity.
AB - A series of chromophores J1-J4 have been synthesized based on julolidine donors
modified with different rigid steric hindrance groups. Compared with the
chromophore (J1) without the isolation group, chromophores J2, J3 and J4 show
better stability. Structural analysis and photophysical property measurements
were carried out to compare the molecular mobility and steric hindrance effect of
the different donor-modified chromophores. All of these chromophores with
isolation groups showed superb thermal stabilities with high thermal
decomposition temperatures above 250 degrees C. Furthermore, with rigid steric
hindrance, chromophores J3 and J4 showed more enhanced thermal stabilities with
thermal decomposition temperatures of 269 degrees C and 275 degrees C,
respectively. Density functional theory was used to calculate the
hyperpolarizability (beta), and the high molecular hyperpolarizability of these
chromophores can be effectively translated into large electro-optic coefficients.
The electro-optic coefficients of poled films containing 20 wt% of these new
chromophores doped in amorphous polycarbonate were 127, 266 and 209 pm V-1 at
1310 nm for chromophores J1-J3, respectively, while the film containing
chromophore J4 showed the largest r33 value of only 97 pm V-1 at 25 wt%. These
results indicated that the introduced isolation group can reduce intermolecular
electrostatic interactions, thus enhancing the macroscopic electro-optic
activity, while the size of the isolation group should be suitable.
PMID- 28425554
TI - On the parallelism between the mechanisms behind chromatography and drug
delivery: the role of interactions with a stationary phase.
AB - A huge number of studies and work in the drug delivery literature are focused on
understanding and modeling transport phenomena, the pivotal point for a good
device design. The rationalization of all phenomena involved is fundamental, but
several concerns arise leaving many issues unsolved. In order to change the point
of view we decided to focus our attention on the parallelisms between two fields
that seem to be very far from each other: chromatography and drug release. Taking
advantages of the studies conducted by many researchers using chromatographic
columns we decided to explain all the phenomena involved in drug delivery
considering sodium ibuprofen (IP) molecules as analytes and hydrogel as a
stationary phase. In particular, we considered not only diffusion, but also drug
polymer interactions as adsorption on the stationary phase and drug-drug
interactions as aggregation of analytes. The hydrogel investigated is a promising
formulation made of agarose and carbomer 974p (AC) loaded with IP, a non
steroidal common anti-inflammatory drug. The self-diffusion coefficient of IP in
AC formulations was measured by using an innovative method based on a magic angle
spinning NMR spectroscopic technique to produce high resolution (liquid-like)
spectra. This method (HR-MAS NMR) is used in combination with pulsed field
gradient spin echo (PGSE) liquid-state techniques. The model predictions
satisfactorily match with the experimental data obtained in water and the gel
environment, indicating that the model presented here, despite its simplicity, is
able to describe the key phenomena governing the device behavior and could be
used to rationalize the experimental activity.
PMID- 28425555
TI - Electrochemical reduction of CO2 on graphene supported transition metals -
towards single atom catalysts.
AB - In this study, we have investigated the use of single metal atoms supported on
defective graphene as catalysts for the electrochemical reduction of CO2 using
the first-principles approach and the computational hydrogen electrode model.
Reaction pathways to produce a variety of C1 products CO, HCOOH, HCHO, CH3OH and
CH4 have been studied in detail for five representative transition metals Ag, Cu,
Pd, Pt, and Co. Different pathways were revealed in contrast to those found for
metallic crystalline surfaces and nanoparticles. These single atom catalysts have
demonstrated a general improvement in rate limiting potentials to generate C1
hydrocarbons. They also show distinct differences in terms of their efficiency
and selectivity in CO2 reduction, which can be correlated with their elemental
properties as a function of their group number in the periodic table. Six best
candidates for CH4 production are identified by conducting computational
screening of 28 d-block transition metals. Ag has the lowest overpotential (0.73
V), and is followed by Zn, Ni, Pd, Pt and Ru with overpotentials all below 1 V.
Cu in the supported single atom form shows a strong preference towards producing
CH3OH with an overpotential of 0.68 V well below the value of 1.04 V for
producing CH4.
PMID- 28425557
TI - Dual spectra band emissive Eu2+/Mn2+ co-activated alkaline earth phosphates for
indoor plant growth novel phosphor converted-LEDs.
AB - This paper reports designing a novel single composition blue/red color
illuminating phosphor followed by fabricating "smart" agricultural/horticultural
LED lighting. Color-tunable Eu2+/Mn2+ co-activated alkaline earth phosphates,
Na(Sr,Ba)PO4 and Ca3Mg3(PO4)4, are considered, and the stable doping sites for
the corresponding activators are identified by using first-principle DFT
calculations. We can realize the designated color purity with stable thermal
quenching preserved luminescence behavior is induced by the Eu2+ center
positioned at different coordination states with intermixed Sr2+/Ba2+ sites in
Na(Sr,Ba)PO4 hosts. Moreover, we demonstrate that the resultant LED lighting
adopting the proposed novel phosphor composition stimulates the enhanced
photosynthesis reaction for indoor hydroponics plants, such as oats and onions,
which is superior to the narrow line emission band induced by the mixture of
conventional red/green/blue LEDs. Thus, using the color-tunable single
composition luminescent material may produce an innovative energy-efficient
artificial lighting for indoor plant growth.
PMID- 28425558
TI - Real-time temperature monitoring with fiber Bragg grating sensor during diffuser
assisted laser-induced interstitial thermotherapy.
AB - High-sensitivity temperature sensors have been used to validate real-time thermal
responses in tissue during photothermal treatment. The objective of the current
study was to evaluate the feasible application of a fiber Bragg grating (FBG)
sensor for diffuser-assisted laser-induced interstitial thermotherapy (LITT)
particularly to treat tubular tissue disease. A 600 - ? m core-diameter diffuser
was employed to deliver 980-nm laser light for coagulation treatment. Both a
thermocouple and a FBG were comparatively tested to evaluate temperature
measurements in ex vivo liver tissue. The degree of tissue denaturation was
estimated as a function of irradiation times and quantitatively compared with
light distribution as well as temperature development. At the closer distance to
a heat source, the thermocouple measured up to 41% higher maximum temperature
than the FBG sensor did after 120-s irradiation (i.e., 98.7 degrees C +/- 6.1
degrees C for FBG versus 131.0 degrees C +/- 5.1 degrees C for thermocouple;
p < 0.001 ). Ex vivo porcine urethra tests confirmed the real-time temperature
measurements of the FBG sensor as well as consistently circumferential tissue
denaturation after 72-s irradiation ( coagulation thickness = 2.2 +/- 0.3 ?? mm
). The implementation of FBG can be a feasible sensing technique to
instantaneously monitor the temperature developments during diffuser-assisted
LITT for treatment of tubular tissue structure.
PMID- 28425559
TI - Multimodal optical setup based on spectrometer and cameras combination for
biological tissue characterization with spatially modulated illumination.
AB - The application of optical techniques as tools for biomedical research has
generated substantial interest for the ability of such methodologies to
simultaneously measure biochemical and morphological parameters of tissue.
Ongoing optimization of optical techniques may introduce such tools as
alternative or complementary to conventional methodologies. The common approach
shared by current optical techniques lies in the independent acquisition of
tissue's optical properties (i.e., absorption and reduced scattering
coefficients) from reflected or transmitted light. Such optical parameters, in
turn, provide detailed information regarding both the concentrations of
clinically relevant chromophores and macroscopic structural variations in tissue.
We couple a noncontact optical setup with a simple analysis algorithm to obtain
absorption and scattering coefficients of biological samples under test.
Technically, a portable picoprojector projects serial sinusoidal patterns at low
and high spatial frequencies, while a spectrometer and two independent CCD
cameras simultaneously acquire the reflected diffuse light through a single
spectrometer and two separate CCD cameras having different bandpass filters at
nonisosbestic and isosbestic wavelengths in front of each. This configuration
fills the gaps in each other's capabilities for acquiring optical properties of
tissue at high spectral and spatial resolution. Experiments were performed on
both tissue-mimicking phantoms as well as hands of healthy human volunteers to
quantify their optical properties as proof of concept for the present technique.
In a separate experiment, we derived the optical properties of the hand skin from
the measured diffuse reflectance, based on a recently developed camera model.
Additionally, oxygen saturation levels of tissue measured by the system were
found to agree well with reference values. Taken together, the present results
demonstrate the potential of this integrated setup for diagnostic and research
applications.
PMID- 28425560
TI - Impact of simulated three-dimensional perception on precision of depth
judgements, technical performance and perceived workload in laparoscopy.
AB - BACKGROUND: This study compared precision of depth judgements, technical
performance and workload using two-dimensional (2D) and three-dimensional (3D)
laparoscopic displays across different viewing distances. It also compared the
accuracy of 3D displays with natural viewing, along with the relationship between
stereoacuity and 3D laparoscopic performance. METHODS: A counterbalanced within
subjects design with random assignment to testing sequences was used. The system
could display 2D or 3D images with the same set-up. A Howard-Dolman apparatus
assessed precision of depth judgements, and three laparoscopic tasks (peg
transfer, navigation in space and suturing) assessed performance (time to
completion). Participants completed tasks in all combinations of two viewing
modes (2D, 3D) and two viewing distances (1 m, 3 m). Other measures administered
included the National Aeronautics and Space Administration Task Load Index
(perceived workload) and the Randot(r) Stereotest (stereoacuity). RESULTS: Depth
judgements were 6.2 times as precise at 1 m and 3.0 times as precise at 3 m using
3D versus 2D displays (P < 0.001). Participants performed all laparoscopic tasks
faster in 3D at both 1 and 3 m (P < 0.001), with mean completion times up to 64
per cent shorter for 3D versus 2D displays. Workload was lower for 3D displays
(up to 34 per cent) than for 2D displays at both viewing distances (P < 0.001).
Greater viewing distance inhibited performance for two laparoscopic tasks, and
increased perceived workload for all three (P < 0.001). Higher stereoacuity was
associated with shorter completion times for the navigating in space task
performed in 3D at 1 m (r = - 0.40, P = 0.001). CONCLUSION: 3D displays offer
large improvements over 2D displays in precision of depth judgements, technical
performance and perceived workload.
PMID- 28425561
TI - Creating homogenous strain distribution within 3D cell-encapsulated constructs
using a simple and cost-effective uniaxial tensile bioreactor: Design and
validation study.
AB - Mechanical loading bioreactors capable of applying uniaxial tensile strains are
emerging to be a valuable tool to investigate physiologically relevant cellular
signaling pathways and biochemical expression. In this study, we have introduced
a simple and cost-effective uniaxial tensile strain bioreactor for the
application of precise and homogenous uniaxial strains to 3D cell-encapsulated
collagen constructs at physiological loading strains (0-12%) and frequencies
(0.01-1 Hz). The bioreactor employs silicone-based loading chambers specifically
designed to stretch constructs without direct gripping to minimize stress
concentration at the ends of the construct and preserve its integrity. The
loading chambers are driven by a versatile stepper motor ball-screw actuation
system to produce stretching of the constructs. Mechanical characterization of
the bioreactor performed through Finite Element Analysis demonstrated that the
constructs experienced predominantly uniaxial tensile strain in the longitudinal
direction. The strains produced were found to be homogenous over a 15 * 4 * 2 mm
region of the construct equivalent to around 60% of the effective region of
characterization. The strain values were also shown to be consistent and
reproducible during cyclic loading regimes. Biological characterization confirmed
the ability of the bioreactor to promote cell viability, proliferation, and
matrix organization of cell-encapsulated collagen constructs. This easy-to-use
uniaxial tensile strain bioreactor can be employed for studying morphological,
structural, and functional responses of cell-embedded matrix systems in response
to physiological loading of musculoskeletal tissues. It also holds promise for
tissue-engineered strategies that involve delivery of mechanically stimulated
cells at the site of injury through a biological carrier to develop a clinically
useful therapy for tissue healing. Biotechnol. Bioeng. 2017;114: 1878-1887. (c)
2017 Wiley Periodicals, Inc.
PMID- 28425562
TI - Couples with Intimate Partner Violence Seeking Relationship Help: Associations
and Implications for Self-Help and Online Interventions.
AB - In-person conjoint treatments for relationship distress are effective at
increasing relationship satisfaction, and newly developed online programs are
showing promising results. However, couples reporting even low levels intimate
partner violence (IPV) are traditionally excluded from these interventions. To
improve the availability of couple-based treatment for couples with IPV, the
present study sought to determine whether associations with IPV found in
community samples generalized to couples seeking help for their relationship and
whether web-based interventions for relationship distressed worked equally well
for couples with IPV. In the first aim, in a sample of 2,797 individuals who were
seeking online help for their relationship, the levels and correlates of both low
intensity and clinically significant IPV largely matched what is found in
community samples. In the second aim, in a sample of 300 couples who were
randomly assigned to a web-based intervention or a waitlist control group, low
impact IPV did not moderate the effects of the intervention for relationship
distress. Therefore, web-based interventions may be an effective (and easily
accessible) intervention for relationship distress for couples with low-intensity
IPV.
PMID- 28425563
TI - Differences in interregional brain connectivity in children with unilateral
hearing loss.
AB - OBJECTIVES: To identify functional network architecture differences in the brains
of children with unilateral hearing loss (UHL) using resting-state functional
connectivity magnetic resonance imaging (rs-fcMRI). STUDY DESIGN: Prospective
observational study. METHODS: Children (7 to 17 years of age) with severe to
profound hearing loss in one ear, along with their normal hearing (NH) siblings,
were recruited and imaged using rs-fcMRI. Eleven children had right UHL; nine had
left UHL; and 13 had normal hearing. Forty-one brain regions of interest culled
from established brain networks such as the default mode (DMN); cingulo-opercular
(CON); and frontoparietal networks (FPN); as well as regions for language,
phonological, and visual processing, were analyzed using regionwise correlations
and conjunction analysis to determine differences in functional connectivity
between the UHL and normal hearing children. RESULTS: When compared to the NH
group, children with UHL showed increased connectivity patterns between multiple
networks, such as between the CON and visual processing centers. However, there
were decreased, as well as aberrant connectivity patterns with the coactivation
of the DMN and FPN, a relationship that usually is negatively correlated.
CONCLUSION: Children with UHL demonstrate multiple functional connectivity
differences between brain networks involved with executive function, cognition,
and language comprehension that may represent adaptive as well as maladaptive
changes. These findings suggest that possible interventions or habilitation,
beyond amplification, might be able to affect some children's requirement for
additional help at school. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:2636-2645,
2017.
PMID- 28425565
TI - Immunolocalization of Jian Carp (Cyprinus Carpio Var. Jian) Cathepsin B: Cloning,
Expression, Characterization, and Antibody Preparation.
AB - Cathepsin B (CatB) cDNA of 759 bp from Jian carp (Cyprinus carpio var. Jian) with
amino acid similarity of 99.6% to common carp was cloned. The mature CatB was
expressed in Escherichia coli BL21 transferred with vector CatB-pET-30a. It was
purified and identified as a single band (29 kDa) on SDS-PAGE. Optimum CatB
activity was observed at 40 degrees C and pH 5.5. Mouse anti-CatB polyclonal
antibody with a high titer of 1:256000 was prepared successfully and shown to
specifically recognize the antigen both in prokaryotic cells and in the tissues
of Jian carp according to western blotting and immunohistochemistry results.
Immunolocation analysis showed that CatB distribution at protein level varied
among the tested tissues. The results presented in this study may provide a
significant reference for future research on the inherent relationship between
CatB and the quality of fish or fish products at both the gene and protein
levels.
PMID- 28425564
TI - Osteoblast role in osteoarthritis pathogenesis.
AB - Even if osteoarthritis pathogenesis is still poorly understood, numerous
evidences suggest that osteoblasts dysregulation plays a key role in
osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been
described in osteoarthritis osteoblasts, which is responsible for abnormal bone
remodeling and decreased mineralization. Alterations in genes expression are
involved in dysregulation of osteoblast function, bone remodeling, and
mineralization, leading to osteoarthritis development. Moreover, osteoblasts
produce numerous transcription factors, growth factors, and other proteic
molecules which are involved in osteoarthritis pathogenesis.
PMID- 28425566
TI - Gender-specific histopathological response in guppies Poecilia reticulata exposed
to glyphosate or its metabolite aminomethylphosphonic acid.
AB - Ecotoxicity of glyphosate (GLY) and its metabolite aminomethylphosphonic acid
(AMPA) was investigated in guppies, Poecilia reticulata. We tested the effects of
these chemicals on the gills and liver of both male and female guppies using
qualitative and quantitative histopathological analyses associated with
histopathological condition indexes. Both genders showed similar median lethal
concentration (LC50 ) at 96 h for GLY (68.78 and 70.87 mg l-1 ) and AMPA (180 and
164.32 mg l-1 ). However, the histopathological assessment of both fish organs
exposed to sublethal concentrations of GLY (35 mg l-1 ) and AMPA (82 mg l-1 ) for
96 h showed a tissue- and gender-specific histopathological response. In both
exposure assays, fish presented mainly progressive changes, such as proliferation
of the interlamellar epithelium, partial and total fusion of secondary lamellae.
The liver showed mainly regressive changes, such as steatosis, pyknotic nuclei
and high distribution of collagen fibers. Unusually large hepatocytes as
degenerated cells were also detected. Histopathological changes in gills were
similar for the males and females, but the liver response was different between
the genders. The hepatic inflammatory changes were more common in males. The
increase in the area of hepatocyte vacuoles is gender dependent with higher
values in the male compared to the female guppies exposed to GLY and AMPA.
Multiparametric analysis indicated that the male guppies are more sensitive than
females, particularly in the presence of AMPA. Our study shows that the
histopathological assessment associated with gender-specific response can be
successfully used in ecotoxicological assessment of GLY and the metabolite AMPA.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425567
TI - Effect of NGF From Venom of Chinese Cobra (Naja Atra)on Chondrocytes
Proliferation and Metabolism In Vitro.
AB - Autologous chondrocyte implantation (ACI) is promising strategy for cartilage
repair. However, chondrocyte phenotype is easily lost when expanded in vitro
which defined as "dedifferentiation." To ensure successful therapy, an effective
pro-chondrogenic agent is necessary to overcome the obstacle of limited cell
numbers in the restoration process, and dedifferentiation is a prerequisite. In
the present study, we investigated the chondro-protective effect of NGF from
Chinese cobra venom on human chondrocytes by determination of its specific effect
on cell viability, proliferation, morphology, GAG production, and cartilage
specific gene expression. The results suggested that NGF showed no cytotoxicity
to chondrocytes below the concentration of 16 ug/mL. DNA and glycosaminoglycan
(GAG) content were, respectively, improved in NGF groups comparing to the control
(P < 0.05). NGF up-regulate the gene expression of ACAN, SOX9, and COL2A1 while
down-regulate the expression level of COL1A1 (P < 0.05). Moreover, the results of
viability assay, hematoxylin-eosin, safranin O, and immunohistochemical staining
also suggested better performances in NGF groups. NGF of 6 ug/mL shown lower
cytotoxicity on chondrocytes, more glycosaminoglycans (GAGs) synthesis and up
regulated chondrogenic gene expression. This study may provide a basis for the
development of a novel agent for the treatment of articular cartilage defects. J.
Cell. Biochem. 118: 4308-4316, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425568
TI - libKEDF: An accelerated library of kinetic energy density functionals.
AB - Kinetic energy density functionals (KEDFs) approximate the kinetic energy of a
system of electrons directly from its electron density. They are used in
electronic structure methods that lack direct access to orbitals, for example,
orbital-free density functional theory (OFDFT) and certain embedding schemes. In
this contribution, we introduce libKEDF, an accelerated library of modern KEDF
implementations that emphasizes nonlocal KEDFs. We discuss implementation details
and assess the performance of the KEDF implementations for large numbers of
atoms. We show that using libKEDF, a single computing node or (GPU) accelerator
can provide easy computational access to mesoscale chemical and materials science
phenomena using OFDFT algorithms. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425569
TI - A Comparative Study of Natural Antimicrobial Delivery Systems for Microbial
Safety and Quality of Fresh-Cut Lettuce.
AB - Nanoencapsulation can provide a means to effectively deliver antimicrobial
compounds and enhance the safety of fresh produce. However, to date there are no
studies which directly compares how different nanoencapsulation systems affect
fresh produce safety and quality. This study compared the effects on quality and
safety of fresh-cut lettuce treated with free and nanoencapsulated natural
antimicrobial, cinnamon bark extract (CBE). A challenge study compared
antimicrobial efficacy of 3 different nanoencapsulated CBE systems. The most
effective antimicrobial treatment against Listeria monocytogenes was chitosan-co
poly-N-isopropylacrylamide (chitosan-PNIPAAM) encapsulated CBE, with a reduction
on bacterial load up to 2 log10 CFU/g (P < 0.05) compared to the other
encapsulation systems when fresh-cut lettuce was stored at 5 degrees C and 10
degrees C for 15 d. Subsequently, chitosan-PNIPAAM-CBE nanoparticles (20, 40, and
80 mg/mL) were compared to a control and free CBE (400, 800, and 1600 MUg/mL) for
its effects on fresh-cut lettuce quality over 15 d at 5 degrees C. By the 10th
day, the most effective antimicrobial concentration was 80 mg/mL for chitosan
PNIPAAM-CBE, up to 2 log10 CFU/g reduction (P < 0.05), compared with the other
treatments. There was no significant difference between control and treated
samples up to day 10 for the quality attributes evaluated. Chitosan-PNIPAAM-CBE
nanoparticles effectively inhibited spoilage microorganisms' growth and extended
fresh-cut lettuce shelf-life. Overall, nanoencapsulation provided a method to
effectively deliver essential oil and enhanced produce safety, while creating
little to no detrimental quality changes on the fresh-cut lettuce.
PMID- 28425570
TI - Elongation of barley roots in high-pH nutrient solution is supported by both cell
proliferation and differentiation in the root apex.
AB - Many crops grow well on neutral or weakly acidic soils. The ability of roots to
elongate under high-external pH would be advantageous for the survival of plants
on alkaline soil. We found that root elongation was promoted in some plant
species in alkaline-nutrient solution. Barley, but not tomato, root growth was
maintained in pH 8 nutrient solution. Fe and Mn were absorbed well from the pH 8
nutrient solution by both barley and tomato plants, suggesting that the different
growth responses of these two species may not be caused by insolubilization of
transition metals. The ability of intact barley and tomato plants to acidify
external solution was comparable; in both species, this ability decreased in
plants exposed to pH 8 nutrient solution for 1 w. Conversely, cell proliferation
and elongation in barley root apices were facilitated at pH 8 as shown by
microscopy and cell-cycle-related gene-expression data; this was not observed in
tomato. We propose that barley adapts to alkaline stress by increasing root
development.
PMID- 28425572
TI - Increased propionate concentration in Lactobacillus mucosae fermented wet brewers
grains and during in vitro rumen fermentation.
AB - AIMS: This study was conducted to isolate and identify propionate-producing
bacteria that can be used as an inoculum in improving wet brewers grains and
rumen fermentation via increasing propionate concentration. METHODS AND RESULTS:
A strain of Lactobacillus that exhibits high levels of propionate production was
identified and characterized as Lactobacillus mucosae 521129 by 16S rRNA gene
sequencing and phylogenetic analyses. Wet brewers grains were fermented through
L. mucosae inoculation and resulted in an increase in propionate concentration.
Fermented wet brewers grains were used in in vitro rumen fermentation and
revealed that L. mucosae-fermented wet brewers grains produced more gas and had
higher accumulations propionate, and total VFA than the control. The fewest
methanogen DNA copies were detected in L. mucosae fermented wet brewers grains.
CONCLUSION: Identified L. mucosae improved the fermentation of wet brewers grains
and the in vitro rumen fermentation via increasing propionate and total VFA
concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented research
provided the identification of L. mucosae 521129 as a propionate producer and was
metabolically profiled. Furthermore, data present the putative application of
this organism in improving the fermentation of wet brewers grains and in vitro
rumen fermentation. This article is protected by copyright. All rights reserved.
PMID- 28425571
TI - Clinical factors affecting costs in patients receiving systemic antifungal
therapy in intensive care units in Greece: Results from the ESTIMATOR study.
AB - : Invasive fungal infections are common in intensive care units (ICUs) but there
is a great variability in factors affecting costs of different antifungal
treatment strategies in clinical practice. To determine factors affecting
treatment cost in adult ICU patients with or without documented invasive fungal
infection receiving systemic antifungal therapy (SAT) we have performed a
prospective, multicentre, observational study enrolling patients receiving SAT in
participating ICUs in Greece. During the study period, 155 patients received SAT
at 14 participating ICUs: 37 (23.9%) for proven fungal infection before treatment
began, 10 (6.5%) prophylactically, 77 (49.7%) empirically and 31 (20.0%) pre
emptively; 66 patients receiving early SAT (55.9%) were subsequently confirmed to
have proven infection with Candida spp. (eight while on treatment). The most
frequently used antifungal drugs were echinocandins (89/155; 57.4%), fluconazole
(31/155; 20%) and itraconazole (20/155; 12.9%). Mean total cost per patient by
SAT strategy was ?20 458 (proven), ?15 054 (prophylaxis), ?23 594 (empiric) and
?22 184 (pre-emptive). Factors associated with significantly increased cost were
initial treatment failure, length of stay (LOS) in ICU before starting SAT (i.e.
from admission until treatment start), fever and proven candidaemia (all P<=.05).
CONCLUSION: Early administration of antifungal drugs was not a substantial
component of total hospital costs. However, there was a significant adverse
impact on costs with increasing LOS in febrile patients in ICU for whom diagnosis
of fungaemia was delayed before starting SAT, and with initial treatment failure.
Awareness of potential candidaemia and initiation of pre-emptive or empirical
strategy as early appropriate treatment may improve ICU patient outcomes while
reducing direct medical costs.
PMID- 28425573
TI - Evaluation of Australian dermatological postoperative patient information
leaflets: Should we have a national checklist?
AB - BACKGROUND/OBJECTIVES: Patient information leaflets (PILs) are frequently
provided to patients following dermatological surgery to provide advice and
reassurance in the community. This evaluation reviewed the guidance specified in
postoperative PILs across the 40 Australian dermatology teaching departments and
clinics. METHODS: All 40 departments and clinics were identified and asked to
provide their postoperative information leaflets on sutured wound care
(preferable) or excision biopsy (September-October 2015). For each PIL, 10
preselected parameters were evaluated. RESULTS: In total, 28/40 (70%) of units
responded. From these units, 11/28 (39.3%) stated they do not use a postoperative
PIL. Of the 17 units that provided PILs, the mode minimum dressing duration was
24 (6/17; 35.3%) and 48 h (6/17; 35.3%). For haemostatic advice, 12 PILs
specified the time to press on a bleeding wound, with the most common advice
being 10 (3/12; 25%) and 20 min (3/12; 25%). Of the 14 PILs that provided
analgesic advice, the mode information suggested using paracetamol only and
avoiding aspirin (4/14, 28.6%). Two or more signs of infection were stated in
11/17 (64.7%) PILs; 7/17 (41.2%) advised applying petroleum jelly to the wound,
almost all PILs highlighted the contact for postoperative problems 16/17 (94.1%),
and 5/17 (29.4%) leaflets mentioned scarring. Altogether 8/17 (47.1%) of PILs
advised on the timeframe until active exercise could resume postoperatively.
CONCLUSION: Guidance provided in Australian postoperative dermatological PILs is
heterogeneous. A consensus checklist or template would be beneficial and ensure
that advice provided to patients is more consistent; this could be adapted for
local factors.
PMID- 28425574
TI - Factors associated with sustainability of 2 quality improvement programs after
achieving early implementation success. A qualitative case study.
AB - RATIONALE, AIMS, AND OBJECTIVES: Sustainability of innovations is a relatively
new concept in health care research and has become an issue of growing interest.
The current study explored factors related to the sustainability of 2
multidisciplinary hospital-based programs 3 to 6 years after achieving early
implementation success. METHOD: An exploratory qualitative study was conducted
into 2 implementation cases, an Enhanced Recovery After Surgery program for
colorectal surgery and a short-stay program for breast cancer surgery.
Semistructured interviews were held with key persons involved in the care process
in 14 hospitals from both cases minimally 3 years after the implementation,
between March 2012 and May 2013. The Consolidated Framework for Implementation
Research was used to direct the development of the interview guide, during data
collection and during analysis. A directed content analysis was performed.
RESULTS: A total of 21 interviews with 26 individuals were held, 18 regarding the
Enhanced Recovery After Surgery case and 8 regarding the short-stay program case.
Respondents mentioned the following factors associated with sustainability of the
programs: modification and adaptability of the program, cost-effectiveness,
institutionalization into existing systems, short communication lines within the
multidisciplinary team, an innovative culture, benefits for patients,
cosmopolitanism, the existence of external policies and incentives, trust and
belief in the program, and spread of the program to other settings. Two factors
are not covered by the Consolidated Framework for Implementation Research, ie,
modification of the program over the years and spread of the program to other
contexts. CONCLUSIONS: The factors associated with sustainability put forward in
both cases were largely the same. Leadership and the implementation project were
not mentioned as having influenced the long-term sustainability of the benefits
achieved. Sustainability of the innovations is influenced by determinants
stemming from all ecological levels of the health care system and demands
continuous effort in the postimplementation phase.
PMID- 28425575
TI - High Dose Supplementation of Vitamin D Affects Measures of Systemic Inflammation:
Reductions in High Sensitivity C-Reactive Protein Level and Neutrophil to
Lymphocyte Ratio (NLR) Distribution.
AB - The prevalence of Vitamin D deficiency is increasing worldwide, which has be
shown to be associated with increased risk of cardiovascular disease (CVD),
autoimmune disease, and metabolic syndrome. These conditions are also associated
with a heightened state of inflammation. The aim of the current study was to
evaluate the effect of vitamin D supplementation on serum C-Reactive Protein
(CRP) level and Neutrophil-to-lymphocyte ratio (NLR) distribution in a large
cohort of adolescent girls. A total of 580 adolescent girls were recruited follow
by evaluation of CRP and hematological parameters before and after
supplementation with vitamin D supplements as 9 of 50000 IU cholecalciferol
capsules for 9 weeks taken at weekly intervals. At baseline, serum hs-CRP level
was 0.9 (95%CI: 0.5-1.8), while this value after intervention was reduced to 0.8
(95%CI: 0.3-1.6; P = 0.007). Similar results were also detected for NLR (e.g.,
NLR level was 1.66 +/- 0.72 and 1.53 +/- 0.67, P = 0.002, before and after
therapy with compliance rate of >95.2%). Moreover, we found an association
between hs-CRP and BMI, triglyceride, white blood cell count, and lymphocytes.
Interestingly we observed a significant reduction in neutrophil count and CRP
level after high dose vitamin D supplementation. Our findings showed that the
high dose supplementation of vitamin D affects measures of systemic inflammation:
reductions in High Sensitivity C-Reactive Protein level and Neutrophil-to
lymphocyte ratio (NLR) distribution. J. Cell. Biochem. 118: 4317-4322, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28425576
TI - Bone Marrow, Adipose, and Lung Tissue-Derived Murine Mesenchymal Stromal Cells
Release Different Mediators and Differentially Affect Airway and Lung Parenchyma
in Experimental Asthma.
AB - Mesenchymal stromal cells (MSCs) from different sources have differential effects
on lung injury. To compare the effects of murine MSCs from bone marrow (BM),
adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling
processes in experimental allergic asthma, female C57BL/6 mice were sensitized
and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the
last challenge, mice received either saline (50 ul, SAL), BM-MSCs, AD-MSCs, or
LUNG-MSCs (105 cells per mouse in 50 ul total volume) intratracheally. At 1 week,
BM-MSCs produced significantly greater reductions in resistive and viscoelastic
pressures, bronchoconstriction index, collagen fiber content in lung parenchyma
(but not airways), eosinophil infiltration, and levels of interleukin (IL)-4, IL
13, transforming growth factor (TGF)-beta, and vascular endothelial growth factor
(VEGF) in lung homogenates compared to AD-MSCs and LUNG-MSCs. Only BM-MSCs
increased IL-10 and interferon (IFN)-gamma in lung tissue. In parallel in vitro
experiments, BM-MSCs increased M2 macrophage polarization, whereas AD-MSCs and
LUNG-MSCs had higher baseline levels of IL-4, insulin-like growth factor (IGF),
and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic
mice promoted reductions in secretion of these mediators, particularly in BM
MSCs. Intratracheally administered BM-MSCs, AD-MSCs, and LUNG-MSCs were
differentially effective at reducing airway inflammation and remodeling and
improving lung function in the current model of allergic asthma. In conclusion,
intratracheal administration of MSCs from BM, AD, and LUNG were differentially
effective at reducing airway inflammation and remodeling and improving lung
function comparably reduced inflammation and fibrogenesis in this asthma model.
However, altered lung mechanics and lung remodeling responded better to BM-MSCs
than to AD-MSCs or LUNG-MSCs. Moreover, each type of MSC was differentially
affected in a surrogate in vitro model of the in vivo lung environment. Stem
Cells Translational Medicine 2017;6:1557-1567.
PMID- 28425577
TI - Postoperative hemorrhage and hospital revisit after transoral robotic surgery.
AB - OBJECTIVES/HYPOTHESIS: To investigate the incidence and complications related to
postoperative hemorrhage (POH) after transoral robotic surgery (TORS). STUDY
DESIGN: Retrospective review of the State Inpatient Database (SID), the State
Ambulatory Surgery Database (SASD), and the State Emergency Department Database
(SEDD) from the Healthcare Cost and Utilization Project. METHODS: Patients were
identified from the SID, SASD, and SEDD for the states of Florida, New York, and
California from 2005 to 2013 who had an International Classification of Diseases,
Ninth Edition code for a surgical procedure on the upper aerodigestive tract
associated with a code for robotic-assisted surgery. Univariate logistic
regression was used to explore factors associated with POH. RESULTS: Five hundred
nine patients underwent TORS. Indications for surgery included neoplastic disease
in 376 (74%) and sleep apnea in 74 (15%). Forty-one (8%) had an episode of POH at
a median of 9 days postoperatively (range = 0-21 days). Twenty-four (5%) required
an intervention related to their POH. Sixteen (3%) required return to the
operating room for control of hemorrhage; 11 (2%) had a severe complication that
required embolization or tracheostomy. Charlson Comorbidity Score of >=3 (odds
ratio [OR] = 3.02, 95% confidence interval [CI] = 1.45-6.30) and a tonsillar
neoplasm (OR = 1.96, 95% CI = 1.03-3.74) were significantly associated with POH.
CONCLUSIONS: The incidence of POH after TORS was low, and few of these patients
had a severe complication related to this event. Medical comorbidity and
tonsillar subsite may be independent risk factors for POH. These data provide a
benchmark for informed decision making in TORS and a basis for further study.
LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2287-2292, 2017.
PMID- 28425578
TI - Survival comparisons of intensive vs. conventional hemodialysis: Pitfalls and
lessons.
AB - The optimal dose of hemodialysis (HD) has not yet been established. As a means of
better approximating the physiology of native kidney function, there has been a
growing interest in intensive HD (an increase in dialysis frequency and/or
duration). Although many studies have demonstrated a survival benefit with
intensive dialysis, results have been conflicting. This controversy stems from
the challenges of randomizing patients to conventional vs. intensive HD
modalities and, therefore, the reliance on observational comparisons that have
been limited by varying definitions for intensive dialysis, differences in
dialysis location and prescription, unavoidable treatment selection bias, and a
potential lack of generalizability. This review will discuss the pitfalls and
complexities surrounding survival comparisons with intensive HD, and identify
important directions for future study.
PMID- 28425579
TI - Myringoplasty Outcomes From the Swedish National Quality Registry.
AB - OBJECTIVES/HYPOTHESIS: Data from patients registered for myringoplasty during
2002 to 2012 in the Swedish National Quality Registry for Myringoplasty. STUDY
DESIGN: Both conventional myringoplasty and fat-graft techniques were used aimed
at healing the tympanic membrane in noninfected ears. METHODS: Analysis was
performed on data in a national database collected from 32 ear, nose, and throat
clinics. Surgical procedures and outcomes, and patient satisfaction from a
questionnaire were studied. RESULTS: The database was comprised of 3,775 surgical
procedures, with follow-up available for analysis. One-third were children under
the age of 15 years. The most common indication for surgery was infection
prophylaxis. The overall healing rate of the tympanic membrane after surgery was
88.5%, with a high mean patient satisfaction. Complications registered were
postoperative infection, tinnitus, or taste disturbance that occurred in 5.8% of
patients. CONCLUSIONS: Swedish results for a large number of patients who
completed myringoplasty are presented. The success rate in this study is
comparable to other studies, and good patient-reported outcome measures of
myringoplasty are presented. Databases for surgical procedures and clinical
audits are systematic processes for continuous learning in healthcare. This study
shows that clinical databases can be utilized to analyze national results of
surgical procedures. LEVEL OF EVIDENCE: 2b Laryngoscope, 127:2389-2395, 2017.
PMID- 28425580
TI - The patient safety climate in healthcare organizations (PSCHO) survey: Short-form
development.
AB - RATIONALE, AIMS, AND OBJECTIVES: Measures of safety climate are increasingly used
to guide safety improvement initiatives. However, cost and respondent burden may
limit the use of safety climate surveys. The purpose of this study was to develop
a 15- to 20-item safety climate survey based on the Patient Safety Climate in
Healthcare Organizations survey, a well-validated 38-item measure of safety
climate. METHODS: The Patient Safety Climate in Healthcare Organizations was
administered to all senior managers, all physicians, and a 10% random sample of
all other hospital personnel in 69 private sector hospitals and 30 Veterans
Health Administration hospitals. Both samples were randomly divided into a
derivation sample to identify a short-form subset and a confirmation sample to
assess the psychometric properties of the proposed short form. RESULTS: The short
form consists of 15 items represented 3 overarching domains in the long-form
scale-organization, work unit, and interpersonal. CONCLUSION: The proposed short
form efficiently captures 3 important sources of variance in safety climate:
organizational, work-unit, and interpersonal. The short-form development process
was a practical method that can be applied to other safety climate surveys. This
safety climate short form may increase response rates in studies that involve
busy clinicians or repeated measures.
PMID- 28425581
TI - Clinical, Biochemical, and Genetic Features of 41 Han Chinese Families With
Primary Hypertrophic Osteoarthropathy, and Their Therapeutic Response to
Etoricoxib: Results From a Six-Month Prospective Clinical Intervention.
AB - Primary hypertrophic osteoarthropathy (PHO) is a rare inherited disease caused by
genetic defects in the prostaglandin metabolism pathway; disturbed prostaglandin
E2 (PGE2 ) catabolism resulting in increased PGE2 level is suggested in the
pathogenesis. Forty-three Han Chinese patients with PHO were studied and 41 of
them were treated. Mutations in the HPGD gene, causing hypertrophic
osteoarthropathy, primary, autosomal recessive 1 (PHOAR1; OMIM 259100), were
identified in seven patients, and mutations in the SLCO2A1 gene, causing
hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2; OMIM
614441), were identified in 36 patients. Clinical phenotypes of PHO varied,
ranging from mild isolated finger clubbing to severe pachydermia and disabling
joint swelling, even within families. Circulating PGE2 metabolism features of
PHOAR2 were different from those of PHOAR1. Different frequency and severity of
pachydermia between the subgroups were also indicated. A percentage of PHOAR2
patients suffered from gastrointestinal hemorrhage, but this symptom was not
observed in the PHOAR1 subgroup. Clinical evidence highlighted the essential role
of sex hormones in prostaglandin transporter regulation with respect to PHOAR2
onset, although no significant associations of urinary PGE2 or PGE-M with sex
hormones were identified. Treatment with etoricoxib, a selective cyclooxygenase-2
inhibitor, was proved to be beneficial and safe. We detected its notable efficacy
in decreasing urinary PGE2 levels in the majority of the enrolled patients during
6 months of intervention; clinical phenotypes assessed, including pachydermia,
finger clubbing, and joint swelling, were improved. We found no visible evidence
of a positive effect of etoricoxib on periostosis; however, significant links
between urinary PGE2 and serum bone turnover markers indicated a potential role
of decreased PGE2 in periostosis management. This is the largest reported cohort
of subjects genetically diagnosed with PHO. For the first time, we systematically
investigated the biochemical and clinical differences between PHOAR1 and PHOAR2,
and prospectively showed the positive efficacy and safety of etoricoxib for PHO
patients. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28425582
TI - Personality, immune response and reproductive success: an appraisal of the pace
of-life syndrome hypothesis.
AB - The pace-of-life syndrome (POLS) hypothesis is an extended concept of the life
history theory that includes behavioural traits. The studies challenging the POLS
hypothesis often focus on the relationships between a single personality trait
and a physiological and/or life-history trait. While pathogens represent a major
selective pressure, few studies have been interested in testing relationships
between behavioural syndrome, and several fitness components including immunity.
The aim of this study was to address this question in the mealworm beetle,
Tenebrio molitor, a model species in immunity studies. The personality score was
estimated from a multidimensional syndrome based of four repeatable behavioural
traits. In a first experiment, we investigated its relationship with two measures
of fitness (reproduction and survival) and three components of the innate
immunity (haemocyte concentration, and levels of activity of the phenoloxidase
including the total proenzyme and the naturally activated one) to challenge the
POLS hypothesis in T. molitor. Overall, we found a relationship between
behavioural syndrome and reproductive success in this species, thus supporting
the POLS hypothesis. We also showed a sex-specific relationship between
behavioural syndrome and basal immune parameters. In a second experiment, we
tested whether this observed relationship with innate immunity could be confirmed
in term of differential survival after challenging by entomopathogenic bacteria,
Bacillus thuringiensis. In this case, no significant relationship was evidenced.
We recommend that future researchers on the POLS should control for differences
in evolutionary trajectory between sexes and to pay attention to the choice of
the proxy used, especially when looking at immune traits.
PMID- 28425583
TI - Sleep apnea syndrome, inflammation and oxidative stress in hemodialysis patients.
AB - INTRODUCTION: Sleep apnea syndrome (SAS) is an established cardiovascular risk
factor in the general population related to inflammation and oxidative stress and
is very common among hemodialysis patients. Cardiovascular disease and its
complications is the main cause of death among hemodialysis patients. The aim of
the present study was to investigate the role of SAS in the promotion of
inflammation and oxidative stress and thus in the augmentation of cardiovascular
risk in hemodialysis patients. METHODS: Thirty-seven hemodialysis patients
underwent an overnight full polysomnography study. The following morning blood
samples were obtained and TNF-alpha (tumor necrosis factor-alpha), IL-6
(interleukin-6), MPO (myeloperoxidase), and oxLDL (oxidized low density
lipoprotein) were measured. FINDINGS: We investigated the correlation of
patients' markers of inflammation and oxidative stress with their sleep
parameters (total sleep time, AHI, apnea/hypopnea index; RDI, respiratory
disturbance index; DI, desaturation index, mean and minimum SpO2 and percentage
of sleep time with SpO2 < 90%). TNF-alpha correlated positively with BMI (r =
0.510, P < 0.0001) and total sleep time (r = 0.370, P = 0.027). IL-6 correlated
positively with age (r = 0.363, P = 0.027), AHI (r = 0.385, P = 0.018), DI (r =
0.336, P = 0.042) and percentage of sleep time with SpO2 < 90% (r = 0.415, P =
0.012) and negatively with mean SpO2 (r = -0.364, P = 0.027). Myeloperoxidase
correlated positively with AHI (r = 0.385, P = 0.018), DI (r = 0.380, P = 0.02)
and percentage of sleep time with SpO2 < 90% (r = 0.388, P = 0.019). Finally,
oxLDL correlated positively with BMI (r = 0.443, P = 0.007), AHI (r = 0.395, P =
0.015), RDI (r = 0.328, P = 0.048) and total sleep time with SpO2 <90% (r =
0.389, P = 0.019). CONCLUSIONS: These results indicate that, in hemodialysis
patients, the severity of SAS and nocturnal hypoxia correlated positively with
markers of inflammation and oxidative stress.
PMID- 28425584
TI - Changes in cIAP2, survivin and BimEL expression characterize the switch from
autophagy to apoptosis in prolonged starvation.
AB - BACKGROUND: Autophagy is a catabolic process involving the engulfment of
cytoplasmic content within autophagosomes followed by their delivery to
lysosomes. This process is a survival mechanism, enabling cells to cope with
nutrient deprivation by degradation and recycling of macromolecules. Yet during
continued stress such as prolonged starvation, a switch from autophagy to
apoptosis is often detected. OBJECTIVE: In this work, we characterized the
temporal dynamics of the transition from autophagy towards apoptosis with the aim
of elucidating the molecular mechanism regulating the switch from survival
autophagy to apoptotic cell death. RESULTS AND CONCLUSIONS: We defined an inverse
relationship between apoptosis and autophagy spanning a period of 72 h,
manifested by the sequential reduction in LC3 lipidation and the activation of
caspase-3. The transition to apoptosis correlated with a selective decline in the
mRNA and protein levels of two anti-apoptotic IAP family proteins, survivin and
cIAP2 and a selective increase in the BH3-only protein, BimEL. This 'molecular
signature' was common to several cell lines undergoing the switch from autophagy
to apoptosis during prolonged starvation. Mechanistically, the increased BimEL
protein levels resulted from its reduced binding to its specific E3 ligase,
betaTrCP, leading to protein stabilization. Consistent with this, BimEL showed
decreased phosphorylation at critical sites previously reported to be essential
for binding to the E3 ligase. The decrease in the anti-apoptotic IAPs and the
increase in the pro-apoptotic BimEL may thus constitute a molecular switch from
autophagy to apoptosis during prolonged starvation.
PMID- 28425585
TI - Eosinophilic esophagitis: unclear roles of IgE and eosinophils.
AB - Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the
oesophagus. Recognized as a distinct entity only two decades ago, the emergence
of the disease along with the availability of new technologies has rapidly opened
new research avenues and outlined the main features of the pathogenesis of EoE.
Yet, each advance in our understanding of the disease has raised new questions
about the previous consensus. Currently, new subsets of the disease challenge our
diagnostic criteria. For instance, it was believed that EoE did not respond to
proton pump inhibitor (PPI) therapy; however, it has now been shown that a
substantial proportion of EoE patients indeed respond to PPIs. In addition, a new
subset of patients not even presenting eosinophil infiltrates in the oesophagus
has also been described. Moreover, approaches for better understanding the
heritability of the disease bring into question the dogma of predominant genetic
involvement. Furthermore, the specificity and sensitivity of allergy testing for
targeted food avoidance is highly controversial, and the production of specific
antibodies in EoE now includes IgG4 in addition to IgE. In conclusion, EoE is
perceived as 'a moving target' and the aim of this review was to summarize the
current understanding of EoE pathogenesis.
PMID- 28425586
TI - Introduction to Nobel Conference: 'The Cell Cycle and Cell Death in Disease'.
PMID- 28425587
TI - Hybrid finite difference/finite element immersed boundary method.
AB - The immersed boundary method is an approach to fluid-structure interaction that
uses a Lagrangian description of the structural deformations, stresses, and
forces along with an Eulerian description of the momentum, viscosity, and
incompressibility of the fluid-structure system. The original immersed boundary
methods described immersed elastic structures using systems of flexible fibers,
and even now, most immersed boundary methods still require Lagrangian meshes that
are finer than the Eulerian grid. This work introduces a coupling scheme for the
immersed boundary method to link the Lagrangian and Eulerian variables that
facilitates independent spatial discretizations for the structure and background
grid. This approach uses a finite element discretization of the structure while
retaining a finite difference scheme for the Eulerian variables. We apply this
method to benchmark problems involving elastic, rigid, and actively contracting
structures, including an idealized model of the left ventricle of the heart. Our
tests include cases in which, for a fixed Eulerian grid spacing, coarser
Lagrangian structural meshes yield discretization errors that are as much as
several orders of magnitude smaller than errors obtained using finer structural
meshes. The Lagrangian-Eulerian coupling approach developed in this work enables
the effective use of these coarse structural meshes with the immersed boundary
method. This work also contrasts two different weak forms of the equations, one
of which is demonstrated to be more effective for the coarse structural
discretizations facilitated by our coupling approach.
PMID- 28425588
TI - Drug resistance reversal by combretastatin-A4 phosphate loaded with doxorubicin
in polymersomes independent of angiogenesis effect.
AB - OBJECTIVES: This study aimed to evaluate that the polymersomes (Ps-DOX-CA4P) dual
loaded with combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) overcame
drug resistance and sensitized tumour cells to chemotherapeutic drugs. METHODS:
Ps-DOX-CA4P were prepared by solvent evaporation method using mPEG-b-PLA as
carriers. The potential capability of CA4P to reverse DOX resistance was verified
by cytotoxicity test, apoptosis assay and cellular uptake of DOX. The comparison
between free drugs and drug-loaded polymersomes was also made on a single-layer
cell model and multicellular tumour spheroids to display the superiority of the
drug vehicles. Furthermore, we put the emphasis on the investigation into
underlying mechanisms for CA4P overcoming DOX resistance. KEY FINDINGS: Results
showed Ps-DOX-CA4P achieved increased uptake of DOX, enhanced cytotoxicity and
apoptotic rate in MCF-7/ADR cells as well as MCF-7/ADR tumour spheroids. The
potential molecular mechanisms may be related to inhibiting P-glycoprotein
function by downregulating protein kinase Calpha, stimulating ATPase activity,
depleting ATP and increasing intracellular reactive oxygen species levels.
CONCLUSIONS: The findings validated the sensitization property of CA4P on DOX
independent of its well-known angiogenesis effect, which would provide a novel
and promising strategy for drug-resistant cancer therapy.
PMID- 28425589
TI - National Rates of Uterine Rupture are not Associated with Rates of Previous
Caesarean Delivery: Results from the Nordic Obstetric Surveillance Study.
AB - BACKGROUND: Previous caesarean delivery and intended mode of delivery after
caesarean are well-known individual risk factors for uterine rupture. We examined
if different national rates of uterine rupture are associated with differences in
national rates of previous caesarean delivery and intended mode of delivery after
a previous caesarean delivery. METHODS: This study is an ecological study based
on data from a retrospective cohort in the Nordic countries. Data on uterine
rupture were collected prospectively in each country as part of the Nordic
obstetric surveillance study and included 91% of all Nordic deliveries.
Information on the comparison population was retrieved from the national medical
birth registers. Incidence rate ratios by previous caesarean delivery and
intended mode of delivery after caesarean were modelled using Poisson regression.
RESULTS: The incidence of uterine rupture was 7.8/10 000 in Finland and 4.6/10
000 in Denmark. Rates of caesarean (21.3%) and previous caesarean deliveries
(11.5%) were highest in Denmark, while the rate of intended vaginal delivery
after caesarean was highest in Finland (72%). National rates of uterine rupture
were not associated with the population rates of previous caesarean but increased
by 35% per 1% increase in the population rate of intended vaginal delivery and in
the subpopulation of women with previous caesarean delivery by 4% per 1% increase
in the rate of intended vaginal delivery. CONCLUSION: National rates of uterine
rupture were not associated with national rates of previous caesarean, but
increased with rates of intended vaginal delivery after caesarean.
PMID- 28425590
TI - Role of upper gastrointestinal contrast studies for suspected malrotation in
neonatal population.
AB - AIM: Upper gastrointestinal (UGI) contrast study is the preferred radiological
investigation to diagnose malrotation of intestine. We aimed to review the role
of UGI contrast in neonates (term and preterm) who were clinically suspected to
have malrotation. METHODS: The study included a retrospective review of medical
charts and radiology reports. RESULTS: A total of 164 newborn infants underwent
UGI contrast study to rule out malrotation during the study period (2006-2015).
Median gestational age at the time of presentation was 38 weeks (interquartile
range: 35.5-39.6 weeks). Median age for clinical presentation was day 2 of life
(interquartile range: 2-5 days). Out of the 164 contrast studies, 112 were
normal, whereas 52 were reported to have malrotation. Of those 52 infants, 47
were confirmed to have malrotation on surgery (positive predictive value: 90). Of
the 112 infants with normal UGI contrasts, nine infants underwent laparotomy for
ongoing clinical symptoms out of which four infants were diagnosed to have
malrotation on laparotomy. There were 22 infants born at gestational age <32
weeks, who underwent UGI contrast studies to rule out malrotation. Their clinical
symptoms were similar to necrotising enterocolitis. Of 22 preterm contrast
studies, six were reported to have malrotation; of these, five had surgically
confirmed malrotation. No complications related to the contrast study were noted
in both term and preterm infants. CONCLUSION: Current study reaffirms the role of
UGI contrast study as the investigation of choice for diagnosis of malrotation,
in both term and preterm infants. UGI contrast is safe and well tolerated even in
preterm infants.
PMID- 28425591
TI - REFLECTIVE FUNCTIONING AND PERSONALITY ORGANIZATION: ASSOCIATIONS WITH NEGATIVE
MATERNAL BEHAVIORS.
AB - The aim of this study was to examine whether mothers who manifest insensitive and
disconnected behaviors in interaction with their infants differ in terms of
maternal reflective functioning (RF), personality organization, and histories of
abuse. A total of 86 mother-infant dyads, 28 of them with histories of abuse,
participated in the study. RF was assessed with the Adult Attachment Interview
(C. George, N. Kaplan, & M. Main, 1985), and personality organization was
assessed with the self-report Inventory of Personality Organization (M.F.
Lenzenweger, J.F. Clarkin, O.F. Kernberg, & P.A. Foelsh, 2001; L. Normandin et
al., 2002), before the birth of the baby. Maternal behaviors were assessed using
the Disconnected and Extremely Insensitive Parenting measure when the infants
were 15 to 18 months old. The results of multivariate analyses of covariance
indicate that both RF and personality organization were associated with
disconnected and extremely insensitive maternal behaviors. Mothers classified as
presenting intrusive/aggressive behaviors had significantly lower RF as well as
significantly more difficulties in personality organization, including reality
testing, identity, and defense mechanisms. Withdrawn and disconnected maternal
behaviors were associated with the combination of difficulties in mentalization
and personality organization rather than difficulties in one specific area. In
sum, the study provides new evidence regarding the importance of a mentalizing
stance about early attachment relationships for the modulation of maternal
behaviors, especially intrusive/aggressive behaviors.
PMID- 28425592
TI - Mesoporous titanium oxide with high-specific surface area as a coating for in
tube solid-phase microextraction combined with high-performance liquid
chromatography for the analysis of polycyclic aromatic hydrocarbons.
AB - Stainless-steel wires coated with mesoporous titanium oxide were placed into a
polyether ether ketone tube for in-tube solid-phase microextraction, and the
coating sorbent was characterized by X-ray diffraction and scanning electron
microscopy. It was combined with high-performance liquid chromatography to build
an online system. Using eight polycyclic aromatic hydrocarbons as the analytes,
some conditions including sample flow rate, sample volume, organic solvent
content, and desorption time were investigated. Under optimum conditions, an
online analysis method was established and provided good linearity (0.03-30
MUg/L), low detection limits (0.01-0.10 MUg/L), and high enrichment factors (77.6
678). The method was applied to determine target analytes in river water and
water sample of coal ash, and the recoveries are in the range of 80.6-106.6 and
80.9-103.5%, respectively. Compared with estrogens and plasticizers, extraction
coating shows better extraction efficiency for polycyclic aromatic hydrocarbons.
PMID- 28425593
TI - Medium-sized nevus spilus of the neck treated with pulsed dye laser.
AB - Patients with large benign melanocytic lesions located on the neck represent a
therapeutic challenge since the neck is a high-risk area for hypertrophic
scarring and/or retraction. When treating a benign, extensive and visible
melanocytic lesion, the choice of therapy mainly depends on the likelihood of
improved cosmesis. We report a case of a 33-year-old woman with a medium-sized
Nevus Spilus located on the neck, successfully treated with four sessions of
pulsed dye laser. We achieved an excellent clinical and cosmetic result in such a
challenging area. No scarring, distortion or significant dyscromia were observed
after 24 months.
PMID- 28425594
TI - Trilobed pedicled superior gluteal artery perforator flap for lumbosacral defect
coverage.
AB - BACKGROUND: There are many available options for the coverage of lumbosacral area
defects. Surgeons usually use the superior gluteal artery perforator flap (SGAP)
by rotational fashion, which risks complications, such as wound dehiscence or
skin necrosis at the Y-point on the donor site due to the tension. In this
report, the authors present the experience of using trilobed pedicled SGAP flaps
in coverage of the lumbosacral area defects. METHODS: From 2011 to 2015, 16
trilobed pedicled SGAP flaps were performed for the coverage of sacral defects in
our facility. The average defect sizes were 9.3 cm * 7.4 cm (ranging from 5 cm *
4 cm to 13 cm * 13 cm ). Trilobed flap were designed to include a reliable
perforator vessel and rotated 90 degrees to the defect. All flaps included only
one perforator vessel. RESULTS: The average of flap sizes were 15.9 cm * 9.2 cm
(ranging from 10 cm * 20 to 5 cm * 15 cm). Two cases of minimal distal margin
necrosis (<1 cm) were reported in the flap tip area. The unviable distal area was
completely healed after the excision and primary closure. All flaps survived
completely. Patients were followed for an average of 14.8 months postoperatively
(ranging 6-20 months). There was no recurrence of the pressure sore during the
follow-up period. CONCLUSION: Trilobed pedicled SGAP flap successfully
reconstructed various sized defects and reduced the distortion and tension of the
wound, minimizing wound complications. This flap could reduce the hospital stay
and the recurrence of the pressure sore.
PMID- 28425595
TI - Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry
based study assessing risk of disability pension.
AB - BACKGROUND: Atopic dermatitis and hand eczema often impair the ability of people
to work. Only a few studies have investigated whether individuals with loss-of
function filaggrin gene (FLG) mutations, who often have severe and early onset of
dermatitis, experience occupational consequences. OBJECTIVE: To investigate the
personal consequences of having atopic dermatitis and/or hand eczema and FLG
mutations. METHOD: Adult Danes from the general population (n = 3247) and
patients with atopic dermatitis and/or hand eczema (n = 496) were genotyped for
common FLG mutations, and completed a questionnaire about skin symptoms and hand
eczema. Socioeconomic variables, including disability pension, and information on
work in risk occupations were retrieved from national registries. The reasons for
granting disability pension were unknown. RESULTS: Disability pension was
associated with hand eczema in the general population, especially among
individuals with a history of atopic dermatitis. Moreover, self-reported hand
eczema and atopic dermatitis were associated with particularly high risk of
disability pension among FLG mutation carriers [odds ratio (OR) 4.02 and 95%
confidence interval (CI): 1.15-14.11; and OR 6.01 and 95%CI: 2.37-15.34,
respectively]. Furthermore, 60% of the FLG mutation carriers with atopic
dermatitis who developed hand eczema had experienced symptoms before adulthood.
CONCLUSION: In the general population, self-reported hand eczema and atopic
dermatitis, particularly in individuals with a genetically impaired skin barrier,
were associated with disability pension, suggesting that FLG mutations carriers
with a history of atopic dermatitis and hand eczema could benefit from early
attention with respect to choice of occupation.
PMID- 28425597
TI - Too many instruments for measuring Quality of Life in Atopic Dermatitis.
PMID- 28425596
TI - Histamine intolerance in chronic urticaria.
PMID- 28425598
TI - Quality of life - an essential parameter for dermatology.
PMID- 28425599
TI - The starch-binding domain family CBM41-An in silico analysis of evolutionary
relationships.
AB - Within the CAZy database, there are 81 carbohydrate-binding module (CBM)
families. A CBM represents a non-catalytic domain in a modular arrangement of
glycoside hydrolases (GHs). The present in silico study has been focused on
starch-binding domains from the family CBM41 that are usually part of
pullulanases from the alpha-amylase family GH13. Currently there are more than
1,600 sequences classified in the family CBM41, almost exclusively from Bacteria,
and so a study was undertaken in an effort to divide the members into relevant
groups (subfamilies) and also to contribute to the evolutionary picture of family
CBM41. The CBM41 members adopt a beta-sandwich fold (~100 residues) with one
carbohydrate-binding site formed by the side-chains of three aromatic residues
that interact with carbohydrate. The family CBM41 can be divided into two basic
subdivisions, distinguished from each other by a characteristic sequence pattern
or motif of the three essential aromatics as follows: (i) "W-W-~10aa-W" (the so
called Streptococcus/Klebsiella-type); and (ii) "W-W-~30aa-W" (Thermotoga-type).
Based on our bioinformatics analysis it is clear that the first and second
positions of the motif can be occupied by aromatic residues (Phe, Tyr, His) other
than tryptophan, resulting in the existence of six different carbohydrate-binding
CBM41 groups, that reflect mostly differences in taxonomy, but which should
retain the ability to bind an alpha-glucan. In addition, three more groups have
been proposed that, although lacking the crucial aromatic motif, could possibly
employ other residues from remaining parts of their sequence for binding
carbohydrate. Proteins 2017; 85:1480-1492. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425600
TI - CAR-T cell manufacturing: time to put it in gear.
PMID- 28425601
TI - The confusion continues: evolving nature of massive transfusion protocol practice
may reflect lack of evidence to support a single solution that fits all.
PMID- 28425602
TI - Implementation of pathogen inactivation technology: how to make the best
decisions?
PMID- 28425603
TI - Encouraging single-unit transfusions: a superior patient blood management
strategy?
PMID- 28425604
TI - Assuring hospital supply of fresh red blood cells for critically ill patients.
PMID- 28425606
TI - A novel B allele with c.28 + 5885C>T substitution in the erythroid cell-specific
regulatory element identified in an individual with phenotype B3.
PMID- 28425607
TI - Reducing the risk of septic transfusion reactions from platelets.
PMID- 28425608
TI - Response to Assuring hospital supply of fresh red blood cells for critically ill
patients.
PMID- 28425609
TI - Clostridium perfringens sepsis masquerading as a hemolytic transfusion reaction.
PMID- 28425610
TI - Bacterial screening of platelet components by National Health Service Blood and
Transplant, an effective risk reduction measure.
AB - BACKGROUND: Bacterial contamination of blood components remains a major cause of
sepsis in transfusion medicine. Between 2006 and 2010 in the 5 years before the
introduction of bacterial screening of platelet (PLT) components by National
Health Service Blood and Transplant (NHSBT), seven cases of PLT component
associated transmission of bacterial infection were recorded for 10 patients,
three of which were fatal. STUDY DESIGN AND METHODS: Sampling of individual PLT
components was undertaken at 36 to 48 hours after donation and tested in the
BacT/ALERT system with 8 mL inoculated into each of aerobic and anaerobic culture
bottles. Bottles were incubated until the end of the 7-day shelf life and initial
reactive bottles were examined for contamination. Bacterial screened time-expired
PLTs were tested as in the screen method. RESULTS: From February 2011 to
September 2015, a total of 1,239,029 PLT components were screened. Initial
reactive, confirmed-positive, and false-positive rates were 0.37, 0.03, and
0.19%, respectively. False-negative cultures, all with Staphylococcus aureus,
occurred on four occasions; three were visually detected before transfusion and
one confirmed transmission resulted in patient morbidity. The NHSBT screening
protocol effectively reduced the number of clinically adverse transfusion
transmissions by 90% in this reporting period, compared to a similar time period
before implementation. Delayed testing of 4515 time-expired PLT units after
screening revealed no positives. CONCLUSION: The implementation of bacterial
screening of PLT components with the NHSBT BacT/ALERT protocol was an effective
risk reduction measure and increased the safety of the blood supply.
PMID- 28425611
TI - A simple assessment tool for evaluation of cadaveric temporal bone dissection.
AB - EDUCATIONAL OBJECTIVE: Objective metrics in skilled-based educational courses
allow trainees and instructors to assess performance and monitor progress. The
objective is to validate a concise, easy-to-use instrument for assessment of
resident skill during a timed cadaveric temporal-bone (CTB) dissection. STUDY
DESIGN: Retrospective analysis. METHODS: An instrument was developed to assess
resident performance on a yearly timed microdissection of CTB. Five
neurotologists participated in the assessment. Each reviewer's score was compared
to the score given by the senior neurotologist each year for every resident.
Spearman's correlation analysis was then used to assess the reproducibility of
the instrument in assessing resident performance. The ability of the instrument
to distinguish among experienced and novice trainees and to demonstrate
improvement with experience were also assessed. RESULTS: The instrument was
created and used for 6 years. Thirty residents were assessed. Correlation of
scores between the senior neurotologist and the other neurotologist together was
very high (r = 0.883, P < 0.001). Three specific tasks distinguished novice from
senior dissectors: posterior canal, opening the membranous labyrinth, and
disruption of the ossicular chain. CONCLUSION: A new instrument for assessment of
resident skill on CTB dissection is presented. The instrument is easy to use, and
scores derived from it are consistent across reviewers. The new instrument
distinguishes experienced trainees from novice trainees, is sensitive to
individual experience, and has proved useful in providing trainees with objective
performance measures. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:451-455, 2018.
PMID- 28425612
TI - Oral Health Programmes in Indigenous Communities Worldwide-Lessons learned from
the field: A qualitative systematic review.
AB - OBJECTIVES: This systematic review examines the evidence on the effectiveness of
programmes that aim to improve the oral health of Indigenous populations
worldwide, as well as presents a qualitative analysis to explore the design and
implementation of these initiatives. METHODS: MEDLINE and EMBASE were searched.
Studies were included if they described an oral health programme for an
Indigenous population in any country worldwide. A thematic synthesis of the
qualitative findings was undertaken for each study's results and discussion
sections. RESULTS: Nineteen studies were included. Sixteen studies reported
positive results, twelve of which reported statistically significant findings.
Three themes regarding design and implementation emerged from the qualitative
analysis: (i) elements of successful programmes, (ii) challenges and barriers to
successful interventions and (iii) suggestions for improvements. CONCLUSIONS:
Successful programmes considered cultural appropriateness in their design
including extensive community engagement before, during and after implementation
to enhance ownership of, and thus participation in the programme. Collaborative
approaches were seen as an advantage, not only with Indigenous communities, but
also with local health providers and organizations, with particular emphasis on
incorporation into existing services. Challenges included low community
participation, unstable funding and staffing issues. In addition, future
programmes should also incorporate advocacy and community development, focus on
changes to public policy, utilize evidence-based interventions that include
traditional models of health, attempt to secure a stable funding base, target
strategies to ensure staff retention and develop interventions that target the
multilevel causes of general and oral health. This review provides an evidence
base that can aid in the successful design, implementation and sustainability of
oral health programmes for Indigenous people in the future.
PMID- 28425613
TI - UVA 1 laser in the treatment of patients with vitiligo.
PMID- 28425614
TI - Stigmatization and self-determination of preregistration nurses: A path analysis.
AB - The concept of stigma and the stigmatizing behaviours of health-care
professionals can have a profound influence on people with mental illness. A key
construct that has been identified as influencing our behaviours is self
determination. As such, in the present study, we attempted to examine the
connection and influence of motivational measures on the stigmatization of
preregistration nurses. Data were collected once using three surveys that
measured the motivational responses and stigmatizing behaviours of
preregistration nurses after an approved mental health clinical placement. Using
a path analysis, the results indicated that psychological needs significantly
influenced preregistration nurses' self-determination towards work. In addition,
self-determination was a significant influence on the stigmatization behaviours
of preregistration nurses. The results of the present study provide initial
empirical evidence that supports the importance of professional self
determination and the potential connection of quality care, as illustrated with
the low stigmatizing behaviours of preregistration nurses who are more self
determined towards their work/career. Because of the significant results of the
present study, it is recommended that future research is needed that uses self
determination theory as a lens to understand the application and importance
within the field of nurse education.
PMID- 28425615
TI - The natural history of subjective tinnitus in adults: A systematic review and
meta-analysis of no-intervention periods in controlled trials.
AB - OBJECTIVES: Tinnitus is a prevalent condition, but little has been published
regarding the natural history of the condition. One technique for evaluating the
long-term progression of the disease is to examine what happens to participants
in the no-intervention control arm of a clinical trial. The aim of this study was
to examine no-intervention or waiting-list data reported in trials, in which
participants on the active arm received any form of tinnitus intervention. DATA
SOURCES: CINAHL, PsychINFO, EMBASE, ASSIA, PubMed, Web of Science, Science
Direct, EBSCO Host, and Cochrane. METHODS: Inclusion criteria followed the PICOS
principles: Participants, adults with tinnitus; Intervention, none; Control, any
intervention for alleviating tinnitus; Outcomes, a measure assessing tinnitus
symptoms using a multi-item patient-reported tinnitus questionnaire. Secondary
outcome measures included multi-item patient-reported questionnaires of mood and
health-related quality of life and measures that quantified change in tinnitus
loudness; Study design, randomized controlled trials or observational studies
utilizing a no-intervention or waiting-list control group. Data were extracted
and standardized mean difference was calculated for each study to enable meta
analysis. RESULTS: The evidence strongly favored a statistically significant
decrease in the impact of tinnitus over time, though there was significant
heterogeneity and clinical significance cannot be interpreted. Outcome data
regarding secondary measures did not demonstrate any clinically significant
change. CONCLUSIONS: Participants allocated to the no-intervention or waiting
list control arm of clinical trials for a tinnitus intervention show a small but
significant improvement in self-reported measures of tinnitus with time; the
clinical significance of this finding is unknown. There is, however, considerable
variation across individuals. These findings support previous work and can
cautiously be used when counseling patients. Laryngoscope, 128:217-227, 2018.
PMID- 28425618
TI - Classifying Adults with Binge Eating Disorder Based on Severity Levels.
AB - The clinical utility of the severity criterion for binge eating disorder (BED),
introduced in the DSM-5 as a means of addressing heterogeneity and variability in
the severity of this disorder, was evaluated in 189 treatment-seeking adults with
(DSM-5) BED. Participants classified with mild, moderate, severe and extreme
severity of BED, based on their weekly frequency of binge eating episodes,
differed significantly from each other in body mass index (BMI), eating disorder
features, putative factors involved in the maintenance process of the disorder,
comorbid mood, anxiety and personality disorders, psychological distress, social
maladjustment and illness-specific functional impairment (medium-to-large effect
sizes). They were also statistically distinguishable in metabolic syndrome
prevalence, even after adjusting for BMI (large effect size), suggesting the
possibility of non-BMI-mediated mechanisms. The implications of the findings,
providing support for the utility of the binge frequency as a severity criterion
for BED, and directions for future research are outlined. Copyright (c) 2017 John
Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 28425617
TI - Some posterior branches of extralaryngeal recurrent laryngeal nerves have motor
fibers.
AB - OBJECTIVES/HYPOTHESIS: Anatomical variations of the recurrent laryngeal nerve
(RLN), such as extralaryngeal branching, are a well-known risk factor for RLN
injury during thyroid surgery. This study aimed to analyze the surgical anatomy
and to investigate the existence of posterior branch motor fibers of
extralaryngeal RLNs. STUDY DESIGN: Prospective consecutive observational study.
METHODS: This was a prospective cohort study of 366 patients between January 2014
and February 2016. Operative data included the type of operation, incidence of
nerve bifurcation, the distances among anatomical landmarks. The motor fibers
were evaluated using neurostimulation with laryngeal palpation. RESULTS: A total
of 667 RLNs at risk were analyzed in this study, and of these 103 (14.5%) nerves
were bifurcated or trifurcated before the laryngeal entry point (LEP). More
extralaryngeal branched RLNs were observed on the right side than on the left
(17.5% vs. 13.3%, P = .294). The mean distance of the LEP point of division was
longer on the left side (16.2 +/- 6.7 mm) than on the right (14.7 +/- 5.9 mm, P =
.132). All branched RLNs had a palpable laryngeal twitch when stimulating
anterior branches. When stimulating posterior branches, 28.2%(29/103) of branched
RLNs showed palpable laryngeal twitch. Overall incidence of posterior motor
branch in total RLNs was 4.3% (29/667). CONCLUSIONS: The motor fibers of the RLN
are all located in the anterior branch, whereas some posterior branches have
motor function. Identification of all of the branches of the RLN may be mandatory
to decrease the risk of postoperative nerve injury. LEVEL OF EVIDENCE: 4.
Laryngoscope, 127:2678-2685, 2017.
PMID- 28425616
TI - Statin use and risk of multiple myeloma: An analysis from the cancer research
network.
AB - Animal and human data suggest statins may be protective against developing
multiple myeloma; however, findings may be biased by the interrelationship with
lipid levels. We investigated the association between statin use and risk of
multiple myeloma in a large US population, with an emphasis on accounting for
this potential bias. We conducted a case-control study nested within 6 US
integrated healthcare systems participating in the National Cancer Institute
funded Cancer Research Network. Adults aged >=40 years who were diagnosed with
multiple myeloma from 1998-2008 were identified through cancer registries (N =
2,532). For each case, five controls were matched on age, sex, health plan, and
membership duration prior to diagnosis/index date. Statin prescriptions were
ascertained from electronic pharmacy records. To address potential biases related
to lipid levels and medication prescribing practices, multivariable marginal
structural models were used to model statin use (>=6 cumulative months) and risk
of multiple myeloma, with examination of multiple latency periods. Statin use 48
72 months prior to diagnosis/index date was associated with a suggestive 20-28%
reduced risk of developing multiple myeloma, compared to non-users. Recent
initiation of statins was not associated with myeloma risk (risk ratio range 0.90
0.99 with 0-36 months latency). Older patients had more consistent protective
associations across all latency periods (risk ratio range 0.67-0.87). Our results
suggest that the association between statin use and multiple myeloma risk may
vary by exposure window and age. Future research is warranted to investigate the
timing of statin use in relation to myeloma diagnosis.
PMID- 28425619
TI - Analysis of mutations in the SOS-1 gene in two Polish families with hereditary
gingival fibromatosis.
AB - OBJECTIVES: To establish whether two families from Malopolska and Mazovia
provinces in Poland are affected by hereditary gingival fibromatosis type 1,
caused by a single-cytosine insertion in exon 21 of the Son-of-Sevenless-1 gene.
MATERIAL AND METHODS: Six subjects with hereditary gingival fibromatosis and five
healthy subjects were enrolled in the study. Gingival biopsies were collected
during gingivectomy or tooth extraction and used for histopathological
evaluation. Total RNA and genomic DNA were purified from cultured gingival
fibroblasts followed by cDNA and genomic DNA sequencing and analysis. RESULTS:
Hereditary gingival fibromatosis was confirmed by periodontal examination, X-ray,
and laboratory tests. Histopathological evaluation showed hyperplastic
epithelium, numerous collagen bundles, and abundant-to-moderate fibroblasts in
subepithelial and connective tissue. Sequencing of exons 19-22 of the Son-of
Sevenless-1 gene did not reveal a single-cytosine insertion nor other mutations.
CONCLUSIONS: Patients from two Polish families under study had not been affected
by hereditary gingival fibromatosis type 1, caused by a single-cytosine insertion
in exon 21 of the Son-of-Sevenless-1 gene. Further studies of the remaining
regions of this gene as well as of other genes are needed to identify disease
related mutations in these patients. This will help to unravel the pathogenic
mechanism of gingival overgrowth.
PMID- 28425620
TI - Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against
Citrullinated Vimentin.
AB - Periarticular bone loss is a long known but yet insufficiently understood
phenomenon in patients with rheumatoid arthritis. This study investigated whether
autoimmunity against citrullinated proteins is causally involved in triggering
periarticular bone loss. Periarticular bone loss was studied in the standard
antigen-induced arthritis (AIA) mouse model with methylated bovine serum albumin
(mBSA) as well as a modified model with mutated citrullinated vimentin (MCV)
alone or in combination with mBSA. Periarticular bone loss, subchondral
osteoclastogenesis, as well as local expression of cytokines, osteoclast genes,
and peptidyl-arginine deiminase (PAD) enzymes were assessed after arthritis
induction. Immune cell and osteoclast precursor infiltration were detected in the
periarticular bone marrow and local lymph nodes. In addition, periarticular bone
loss was assessed upon challenge of mice with purified anti-MCV antibody. Despite
inducing a milder form of arthritis than mBSA, MCV triggered significant
periarticular bone loss associated with an increased infiltration of osteoclast
precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced
the expression of the osteoclast inducers RANKL and M-CSF, the cytokines IL-8, IL
1, IL-6, and TNF-alpha, as well as PAD2 and PAD4 enzymes in the periarticular
bone marrow. Furthermore, also anti-MCV antibody challenge induced significant
periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity
against citrullinated vimentin triggers periarticular bone loss by osteoclast
activation in the bone marrow. These findings may explain why periarticular bone
loss is already found very early in the disease course of patients with
rheumatoid arthritis. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28425621
TI - p53-competent cells and p53-deficient cells display different susceptibility to
oxygen functionalized graphene cytotoxicity and genotoxicity.
AB - Due to the distinctive physical, electrical, and chemical properties of graphene
nanomaterials, numerous efforts pursuing graphene-based biomedical and industrial
applications are underway. Oxidation of pristine graphene surfaces mitigates its
otherwise hydrophobic characteristic thereby improving its biocompatibility and
functionality. Yet, the potential widespread use of oxidized graphene derivatives
raises concern about adverse impacts on human health. The p53 tumor suppressor
protein maintains cellular and genetic stability after toxic exposures. Here, we
show that p53 functional status correlates with oxygen functionalized graphene (f
G) cytotoxicity and genotoxicity in vitro. The f-G exposed p53-competent cells,
but not p53-deficient cells, initiated G0 /G1 phase cell cycle arrest, suppressed
reactive oxygen species, and entered apoptosis. There was p53-dependent f-G
genotoxicity evident as increased structural chromosome damage, but not increased
gene mutation or chromatin loss. In conclusion, the cytotoxic and genotoxic
potential for f-G in exposed cells was dependent on the p53 functional status.
These findings have broad implications for the safe and effective implementation
of oxidized graphene derivatives into biomedical and industrial applications.
Published 2017. This article has been contributed to by US Government employees
and their work is in the public domain in the USA.
PMID- 28425623
TI - Volunteerism, and alignment, are needed for a major paradigm shift in approaches
to hypertension control: 2016 World Hypertension League Excellence Award in
Hypertension Prevention and Control and the Distinguished Service Award.
PMID- 28425622
TI - Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With
Osteomalacia-like Bone Phenotype.
AB - Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations,
exhibits multi-system abnormalities, including skeletal deformities in humans.
Osteocytes play critical roles in controlling bone modeling and remodeling.
However, the role of neurofibromin, the protein product of the NF1 gene, in
osteocytes is largely unknown. This study investigated the role of neurofibromin
in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout
(Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an
osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in
cKO mice compared with age-matched controls. In addition, calcium-phosphorus
metabolism was significantly altered (calcium reduced; phosphorus reduced;
parathyroid hormone [PTH] increased; 1,25(OH)2 D decreased). Bone
histomorphometry showed dramatically increased osteoid parameters, including
osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed
reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP
staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and
porous cortical bones in the cKO mice, in which osteocyte dendrites were
disorganized as assessed by electron microscopy. Interestingly, the cKO mice
exhibited spontaneous fractures in long bones, as found in NF1 patients.
Mechanical testing of femora revealed significantly reduced maximum force and
stiffness. Immunohistochemistry showed significantly increased FGF23 protein in
the cKO bones. Moreover, primary osteocytes from cKO femora showed about
eightfold increase in FGF23 mRNA levels compared with control cells. The
upregulation of FGF23 was specifically and significantly inhibited by PI3K
inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1
deficient osteocytes. Taken together, these results indicate that Nf1 deficiency
in osteocytes dramatically increases FGF23 production and causes a mineralization
defect (ie, hyperosteoidosis) via the alteration of calcium-phosphorus
metabolism. This study demonstrates critical roles of neurofibromin in osteocytes
for osteoid mineralization. (c) 2017 American Society for Bone and Mineral
Research.
PMID- 28425624
TI - A Statistical Approach to Fine Mapping for the Identification of Potential Causal
Variants Related to Bone Mineral Density.
AB - Although genomewide association studies (GWASs) have been able to successfully
identify dozens of genetic loci associated with bone mineral density (BMD) and
osteoporosis-related traits, very few of these loci have been confirmed to be
causal. This is because in a given genetic region there may exist many trait
associated SNPs that are highly correlated. Although this correlation is useful
for discovering novel associations, the high degree of linkage disequilibrium
that persists throughout the genome presents a major challenge to discern which
among these correlated variants has a direct effect on the trait. In this study
we apply a recently developed Bayesian fine-mapping method, PAINTOR, to determine
the SNPs that have the highest probability of causality for femoral neck (FNK)
BMD and lumbar spine (LS) BMD. The advantage of this method is that it allows for
the incorporation of information about GWAS summary statistics, linkage
disequilibrium, and functional annotations to calculate a posterior probability
of causality for SNPs across all loci of interest. We present a list of the top
10 candidate SNPs for each BMD trait to be followed up in future functional
validation experiments. The SNPs rs2566752 (WLS) and rs436792 (ZNF621 and CTNNB1)
are particularly noteworthy because they have more than 90% probability to be
causal for both FNK and LS BMD. Using this statistical fine-mapping approach we
expect to gain a better understanding of the genetic determinants contributing to
BMD at multiple skeletal sites. (c) 2017 American Society for Bone and Mineral
Research.
PMID- 28425625
TI - A missense mutation in damage-specific DNA binding protein 2 is a genetic risk
factor for limbal squamous cell carcinoma in horses.
AB - Squamous cell carcinoma (SCC) is the most common cancer of the equine eye,
frequently originating at the limbus, with the potential to invade the cornea,
cause visual impairment, and result in loss of the eye. Several breeds of horses
have a high occurrence of limbal SCC implicating a genetic basis for limbal SCC
predisposition. Pedigree analysis in the Haflinger breed supports a simple
recessive mode of inheritance and a genome-wide association study (N = 23)
identified a 1.5 Mb locus on ECA12 significantly associated with limbal SCC
(Pcorrected = 0.04). Sequencing the most physiologically relevant gene from this
locus, damage specific DNA binding protein 2 (DDB2), identified a missense
mutation (c.1013 C > T p.Thr338Met) that was strongly associated with limbal SCC
(P = 3.41 * 10-10 ). Genotyping 42 polymorphisms narrowed the ECA12 candidate
interval to 483 kb but did not identify another variant that was more strongly
associated. DDB2 binds to ultraviolet light damaged DNA and recruits other
proteins to perform global genome nucleotide excision repair. Computational
modeling predicts this mutation to be deleterious by altering conformation of the
beta loop involved in photolesion recognition. This DDB2 variant was also
detected in two other closely related breeds with reported cases of ocular SCC,
the Belgian and the Percheron, suggesting it may also be a SCC risk factor in
these breeds. Furthermore, in humans xeroderma pigmentosum complementation group
E, a disease characterized by sun sensitivity and increased risk of cutaneous SCC
and melanomas, is explained by mutations in DDB2. Cross-species comparison
remains to be further evaluated.
PMID- 28425626
TI - Non-cosmetic dermatological use of botulinum neurotoxin.
PMID- 28425627
TI - Relationship between parent knowledge of child sleep, and child sleep practices
and problems: A pilot study in a children's hospital cohort.
AB - AIM: To describe parent reports of sleep practices, and examine associations with
parent knowledge of child sleep, and whether children's sleep practices differ
between parents who underestimated, overestimated or accurately estimated
children's sleep needs. METHODS: Parents of children aged 2-12 years (n = 115)
attending hospital inpatient or day wards were approached and asked to report
child sleep routines, sleep problems, parent education, household income and
parent knowledge of child sleep via questionnaire. RESULTS: Younger age was
associated with earlier bedtimes and wake times, shorter sleep latencies, longer
sleep durations and greater sleep problems (P < 0.05). Parents from higher income
homes reported earlier bedtimes and wake times, shorter sleep latencies and fewer
sleep problems (P < 0.05). Parents with higher education reported shorter sleep
latencies (P < 0.05). Parents with greater knowledge about child sleep reported
earlier weekday and weekend bedtimes (r s >= 0.26) and wake times (r s >= 0.21)
and greater consistency between their child's weekend and weekday sleep routines
(P < 0.05). In comparison with parents who correctly estimated their child's
sleep needs: parents who underestimated reported later weekday bedtimes (on
average, 46 min), and longer sleep latencies (17 min); parents who overestimated
reported longer sleep latencies (22 min). These findings remained significant
when controlling for child age (P < 0.05). CONCLUSION: Parents with increased
sleep knowledge, higher incomes and higher levels of education were more likely
to report earlier bedtimes, wake times and more consistent sleep routines for
their children.
PMID- 28425628
TI - Validating the proposed ICD-11 domains: A comment on Mulder et al. (2016).
PMID- 28425629
TI - Exploring the concept of "caring cultures": A critical examination of the
conceptual, methodological and validity issues with the "caring cultures"
construct.
AB - AIMS AND OBJECTIVES: To critically examine the conceptual, methodological and
validity issues with the "caring cultures" construct. BACKGROUND: Post the
Francis Report, "caring cultures" and alternative terminology such as "culture/s
of care/caring/compassionate care" have gained prominence in the literature,
especially within a UK policy context. However, in order to understand the value
these "caring cultures" hold in terms of clinical practice, the concept itself
first needs to be understood. DESIGN: A discussion and critical examination of
the concept of "caring cultures" and associated terminology. METHODS: Grey
literature, database, library and reference list searches were conducted.
RESULTS: It is implied that "caring cultures" influence patient care. However,
evidence which verifies this assertion is limited. In this article, the concept
of "caring cultures" is deconstructed and its validity explored. An alternative
to "caring cultures" is proposed in terms of research, whereby the concept of
culture is instead explored in detail, on a microsystem level, using appropriate
methodology. CONCLUSION: The concept of "caring cultures", although attractive in
terms of its apparent simplicity, is not considered the most useful nor
appropriate phrases in terms of advancing research. Instead, research which
examines the established concept of "culture" in relation to outcomes such as
patient care, doing so with an appropriate methodology, is viewed as a more
suitable alternative. RELEVANCE TO CLINICAL PRACTICE: Clarifying concepts and
terminology relating to "caring cultures" is essential for research to progress
and the impact of culture on clinical practice to be better understood.
PMID- 28425630
TI - Earth-Abundant Chalcogenide Photovoltaic Devices with over 5% Efficiency Based on
a Cu2 BaSn(S,Se)4 Absorber.
AB - In recent years, Cu2 ZnSn(S,Se)4 (CZTSSe) materials have enabled important
progress in associated thin-film photovoltaic (PV) technology, while avoiding
scarce and/or toxic metals; however, cationic disorder and associated band
tailing fundamentally limit device performance. Cu2 BaSnS4 (CBTS) has recently
been proposed as a prospective alternative large bandgap (~2 eV), environmentally
friendly PV material, with ~2% power conversion efficiency (PCE) already
demonstrated in corresponding devices. In this study, a two-step process (i.e.,
precursor sputter deposition followed by successive sulfurization/selenization)
yields high-quality nominally pinhole-free films with large (>1 um) grains of
selenium-incorporated (x = 3) Cu2 BaSnS4-x Sex (CBTSSe) for high-efficiency PV
devices. By incorporating Se in the sulfide film, absorber layers with 1.55 eV
bandgap, ideal for single-junction PV, have been achieved within the CBTSSe
trigonal structural family. The abrupt transition in quantum efficiency data for
wavelengths above the absorption edge, coupled with a strong sharp
photoluminescence feature, confirms the relative absence of band tailing in
CBTSSe compared to CZTSSe. For the first time, by combining bandgap tuning with
an air-annealing step, a CBTSSe-based PV device with 5.2% PCE (total area 0.425
cm2 ) is reported, >2.5* better than the previous champion pure sulfide device.
These results suggest substantial promise for the emerging Se-rich Cu2 BaSnS4-x
Sex family for high-efficiency and earth-abundant PV.
PMID- 28425631
TI - Restraint stress increases prolactin-mediated phosphorylation of signal
transducer and activator of transcription 5 in the hypothalamus and adrenal
cortex in the male mouse.
AB - Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the
anterior pituitary. Its rate of secretion is primarily regulated by a negative
feedback mechanism where prolactin stimulates the activity of the
tuberoinfundibular dopaminergic (TIDA) neurones, increasing their release of
dopamine, which accesses the pituitary via the median eminence to suppress
further prolactin secretion. In addition to its well established role in
lactation, circulating prolactin is secreted in response to stress, although the
mechanism by which this is achieved or its cellular targets remains unknown. In
the present study, we show that 15 minutes of restraint stress causes an
approximately seven-fold increase in circulating prolactin concentration in male
mice. Monitoring prolactin receptor activation, using immunohistochemistry to
determine the level and distribution of tyrosine phosphorylated signal transducer
and activator of transcription 5 (pSTAT5), we show that this stress-induced
increase in prolactin interacts with both central and peripheral targets.
Restraint stress for 15 minutes significantly increased pSTAT5 staining in the
arcuate nucleus, median eminence and the zona fasciculata of the adrenal cortex.
In each case, this response was prevented by pretreating the animals with
bromocriptine to block prolactin secretion from the pituitary. Interestingly, in
contrast to many cells in the arcuate nucleus, stress reduced pSTAT5 staining of
the TIDA neurones (identified by dual-labelling for tyrosine hydroxylase). This
suggests that there is reduced prolactin signalling in these cells and thus
potentially a decline in their inhibitory influence on prolactin secretion. These
results provide evidence that prolactin secreted in response to acute stress is
sufficient to activate prolactin receptors in selected target tissues known to be
involved in the physiological adaptation to stress.
PMID- 28425633
TI - Biotechnology and Bioengineering: Volume 114, Number 6, June 2017.
PMID- 28425632
TI - Electrode assisted production of chemicals using Shewanella oneidensis.
PMID- 28425634
TI - CO2 stripping model: Gas saturated with CO2.
PMID- 28425635
TI - Adapting viral safety assurance strategies to continuous processing of biological
products.
PMID- 28425636
TI - Evolving technologies enabling patient-specific bone scaffolds.
PMID- 28425638
TI - De novo design of peptide binding antibodies.
PMID- 28425639
TI - Designing dual inhibitors of Mdm2/MdmX: Unexpected coupling of water with
gatekeeper Y100/99.
AB - Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet
dual inhibitors are challenging to design due to differences in the conformations
of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99.
Analysis of crystal structures and molecular dynamics (MD) simulations of
complexes of Mdm2 and MdmX resulted in the identification of a water molecule
with a long residence time that appears to be modulated by the conformation of
Y100/99. These observations lead us to speculate that dual inhibitors either (i)
stabilize both Mdm2 and MdmX with Y100/99 in the open conformation typically seen
in complexes of Mdm2 with p53, or (ii) the dual inhibitors are agnostic to the
conformation of Y100/99. The recently developed potent dual inhibitory stapled
peptide Atsp7041 appears to be agnostic to the conformation of the gatekeeper
residue. Proteins 2017; 85:1493-1506. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425640
TI - Profiling of the silica-induced molecular events in lung epithelial cells using
the RNA-Seq approach.
AB - Silicosis is a prolonged, irreversible and incurable occupational disease, and
there is a significant number of newly diagnosed cases every year in Hong Kong.
Due to the long latency of the disease, the diagnosis can be missed until
detailed clinical examination at a later stage. For a better control of this
deadly disease, detailing the pro-inflammatory and fibrotic events in the
macrophage would be instrumental in understanding the pathogenesis of the disease
and essential for the significant biomarkers discovery. In this in vitro study,
human cell line model A549 lung epithelial cells were used. The immediate
molecular events underneath the activation of quartz silica polymorphs were
followed in a time course of 0, 0.5, 2, 8, 16 and 24 h. The transcriptome library
was prepared and subjected to RNA-Seq analysis. Data analysis was performed by
pathway analysis tools and verified by real-time PCR. The results showed that
triggered genes were mainly found in the immune response and inflammatory
pathways. An interesting finding was the association of the DNA-binding protein
inhibitor (ID) family in the silica exposure to lung cells. The linkage of ID1,
ID2 and ID3 to cancer may rationalize themselves to be the markers indicating an
early response of silicosis. However, further studies are required to consolidate
the roles of these genes in silicosis. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425642
TI - The PRIAMO study: urinary dysfunction as a marker of disease progression in early
Parkinson's disease.
AB - BACKGROUND AND PURPOSE: New venues are currently being explored to predict
disease progression in Parkinson's disease (PD), such as non-motor subtypes and
models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585
patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the
present 24-month longitudinal prospective analysis aimed to demonstrate that
urinary dysfunction is an early marker of higher motor and non-motor burden as
well as lower health-related quality of life. METHODS AND RESULTS: Multivariable
mixed-effect logistic regression models controlling for demographic and clinical
variables showed that the following NMS domains were associated with urinary
dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI)
1.67-3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18-4.17, P = 0.013),
skin (OR 1.81, 95% CI 1.06-3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34-3.16, P
= 0.001), pain (OR 1.85, 95% CI 1.21-2.83, P = 0.004), fatigue (OR 2.40, 95% CI
1.56-3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72-4.52, P < 0.001) and
respiratory (OR 1.82, 95% CI 1.02-3.23, P = 0.039). Analysis also demonstrated
that urinary dysfunction was associated with higher motor disability (coefficient
1.73, 95% CI 0.68-2.78, P = 0.001) and lower health-related quality of life
(coefficient -0.05, 95% CI -0.08 to -0.02, P < 0.001, and coefficient -3.49, 95%
CI -5.21 to -1.77, P < 0.001) but not with more severe cognitive disability
(coefficient -0.34, 95% CI -0.92 to 0.24, P = 0.251). CONCLUSIONS: This is the
first prospective longitudinal study involving a large cohort of PD patients
demonstrating the relevance of urinary dysfunction as an early marker of higher
motor and non-motor disability as well as lower health-related quality of life.
These findings support a role for urinary dysfunction as an early marker of more
severe disease progression.
PMID- 28425643
TI - Chemical Activation in Blood Serum and Human Cell Culture: Improved Ruthenium
Complex for Catalytic Uncaging of Alloc-Protected Amines.
AB - Chemical (as opposed to light-induced) activation of caged molecules is a rapidly
advancing approach to trigger biological processes. We previously introduced the
ruthenium-catalyzed release of allyloxycarbonyl (alloc)-protected amines in human
cells. A restriction of this and all other methods is the limited lifetime of the
catalyst, thus hampering meaningful applications. In this study, we addressed
this problem with the development of a new generation of ruthenium complexes for
the uncaging of alloc-protected amines with superior catalytic activity. Under
biologically relevant conditions, we achieved a turnover number >300, a reaction
rate of 580 m-1 s-1 , and we observed high activity in blood serum. Furthermore,
alloc-protected doxorubicin, as an anticancer prodrug, could be activated in
human cell culture and induced apoptosis with a single low dose (1 MUm) of the
new catalyst.
PMID- 28425641
TI - Molecular dynamics simulations of early steps in RNA-mediated conversion of
prions.
AB - The rate-limiting step in prion diseases is the initial transition of a prion
protein from its native form into a mis-folded state in which the protein not
only forms cell-toxic aggregates but also becomes infectious. Recent experiments
implicate polyadenosine RNA as a possible agent for generating the initial seed.
In order to understand the mechanism of RNA-mediated mis-folding and aggregation
of prions, we dock polyadenosine RNA to mouse and human prion models. Changes in
stability and secondary structure of the prions upon binding to polyadenosine RNA
are evaluated by comparing molecular dynamics simulations of these complexes with
that of the unbound prions.
PMID- 28425644
TI - Different effects of rotigotine and ropinirole on cholinergic transmission in the
mouse medial prefrontal cortex.
PMID- 28425645
TI - Precutting endoscopic mucosal resection for colorectal lesions.
PMID- 28425646
TI - Endoscopic detection of superficial esophagogastric junction adenocarcinoma.
PMID- 28425647
TI - Can endoscopic stone retraction be carried out even in cases with severe acute
cholangitis?
PMID- 28425648
TI - Balloon overtube can improve maneuverability of the endoscope during colorectal
endoscopic submucosal dissection.
PMID- 28425649
TI - Efficacy of hybrid endoscopic submucosal dissection (ESD) as a rescue treatment
in difficult colorectal ESD cases.
AB - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD), which provides a
higher en bloc resection rate than conventional endoscopic mucosal resection
(EMR), is considered to be a useful treatment option for large colorectal tumors.
However, colorectal ESD is not widely used because of its technical difficulty,
risk of complications and time required. To overcome these drawbacks, a simpler
modified technique, ESD with snaring (hybrid ESD), has been developed. The aim of
the present study was to retrospectively compare the safety and efficacy of
hybrid ESD and conventional ESD for colorectal tumors. METHODS: Between September
2008 and June 2016, ESD was carried out on 137 lesions and hybrid ESD on 27
lesions. All hybrid ESD cases were carried out as a rescue treatment in difficult
ESD cases. We retrospectively investigated procedure time, and the rates of en
bloc resection, perforation, bleeding, and local recurrence. RESULTS: In the
hybrid ESD group, procedure time was shorter compared with the ESD group (108 +/-
59.5 min vs 122 +/- 72.2 min), but the en bloc resection rate was lower (66.7% vs
94.2%). However, there were no significant differences in procedure time, or in
rates of en bloc resection, perforation and bleeding between the two groups.
Local recurrence did not develop in any of our cases. CONCLUSIONS: Hybrid ESD as
a rescue treatment in difficult ESD cases may be less effective for en bloc
resection of large colorectal tumors. Indication for hybrid ESD may be limited to
scheduled treatment from the outset and emergency cases with patients who present
unstable vital signs during ESD.
PMID- 28425650
TI - Current strategies for endoscopic management of acute cholangitis.
AB - BACKGROUND AND AIM: At the pancreatobiliary session of Endoscopic Forum Japan
(EFJ) 2016, current strategies for the endoscopic management of acute cholangitis
were discussed. The topics consisted of two major parts, namely endoscopic
management of acute cholangitis caused by common bile duct stones (CBDS) and
biliary stent occlusion. METHODS: Endoscopists from nine Japanese high-volume
centers along with two overseas centers participated in the questionnaires and
discussion. RESULTS: Strategies for management of cholangitis due to CBDS were
agreed upon, and the clinical guideline of acute cholangitis (Tokyo guidelines
2013) was accepted. The best timing for drainage in Grade 2 (moderate)
cholangitis urgent or early (<24 h) was inconclusive, and more data is required
on this issue. Another controversy was the feasibility of one step stone
extraction in the patient with cholangitis vs stone removal after the cholangitis
had resolved. There were various opinions with regards to the management of acute
cholangitis due to stent occlusion, and the strategies differed according to the
stricture location (distal or hilar) and stent type initially placed (Covered or
uncovered metal stent). CONCLUSION: Strategies for management of cholangitis
caused by CBD stones are well established according to the TG13. More evidence is
required before further recommendations can be made with regards to cholangitis
due to stent occlusion. We aim to clarify this in the near future with
questionnaires and consensus from experts.
PMID- 28425651
TI - Underwater endoscopic mucosal resection for a superficial polyp located at the
anastomosis after surgical colectomy.
PMID- 28425652
TI - Endoscopic findings of esophagogastric junction in children.
AB - Esophagogastric landmarks are recognizable in the same way both in children and
in adults, and palisade-shaped vessels can be observed at the distal position of
esophageal mucosa, even in infants. Few studies have been done in respect to
Barrett's esophagus (BE) in children. Incidence of endoscopically suspected BE
among all children undergoing esophagogastroduodenoscopy (EGD) is approximately
0.25-1.4%, but can be up to 9.7% in patients with gastroesophageal reflux disease
(GERD). Some data suggest that BE is an acquired disorder and point to the
possibility of a congenital component in combination with severe mucosal injury.
Recent reports noted that multilayered epithelium (ME), which shows morphological
and immunocytochemical characteristics of both squamous and columnar epithelium,
is associated with goblet cell metaplasia in adult patients with columnar-lined
esophagus. The role of ME in the development of intestinal metaplasia in children
is uncertain. Furthermore, detailed mechanisms about how short-segment BE (SSBE)
changes to long-segment BE (LSBE) are not yet well understood. Further studies
are required to understand the pathological esophagogastric junction (EGJ) and BE
in children based on reliable epidemiological data and analysis especially in
children who have reflux symptoms. Better understanding of the pediatric EGJ and
BE may allow improved diagnosis, monitoring, therapy and, therefore, prognosis of
GERD-related disorders in adulthood.
PMID- 28425654
TI - Is addition of endoscopic sphincterotomy before endoscopic biliary drainage
necessary for acute cholangitis as a result of common bile duct stones?
PMID- 28425653
TI - Endoscopic gastric mucosal atrophy distinguishes the characteristics of
superficial esophagogastric junction adenocarcinoma.
AB - BACKGROUND AND AIM: Western studies have suggested two distinct etiologies of
esophagogastric junction (EGJ) cancer: Helicobacter pylori-associated atrophic
gastritis and non-atrophic gastric mucosa resembling esophageal adenocarcinoma.
The present study investigated whether endoscopic gastric mucosal atrophy can
distinguish between these two types of EGJ adenocarcinoma. METHODS: Data were
collected from patients with Siewert type II, T1 EGJ adenocarcinoma who underwent
endoscopic or surgical resection at eight Japanese institutions in 2010-2015.
Clinicopathological characteristics of EGJ cancers with and without endoscopic
gastric mucosal atrophy were compared. EGJ was defined as the lower end of the
palisade vein and/or the top of the gastric folds. RESULTS: Of the 229 patients
identified, 161 had endoscopic gastric mucosal atrophy and 68 did not. The latter
group was younger (64 vs 70 years, P = 0.000); had a higher proportion of
patients negative for H. pylori (90% vs 47%, P < 0.0001); and had higher rates of
gastroesophageal reflux disease symptoms (43% vs 12%, P = 0.017), mucosal breaks
(25% vs 15%, P = 0.009), Barrett's esophagus (BE, 78% vs 42%, P < 0.0001), and
tumors above the EGJ (81% vs 19%, P < 0.0001) and on the upper-right side (74% vs
38%, P < 0.0001) than the former group. Multivariate analysis showed that H.
pylori positivity (odds ratio [OR] = 13.0, P < 0.001), long-segment BE (OR =
0.025, P = 0.033), and longitudinal (OR = 8.6, P = 0.001) and circumferential (OR
= 4.7, P = 0.006) tumor locations were independently associated with gastric
mucosal atrophy. CONCLUSION: Two distinct types of EGJ cancer were identified,
with and without endoscopic gastric mucosal atrophy. These types were associated
with different tumor locations.
PMID- 28425655
TI - Memorial Address for Dr Masatsugu Nakajima.
PMID- 28425656
TI - Considering the esophagogastric junction as a 'zone'.
AB - Siewert's classification of adenocarcinoma of the esophagogastric junction (EGJ)
classifies tumors anatomically for determining the appropriate surgical
technique. According to this classification, a type II tumor, true carcinoma of
the cardia, is defined as a cancer within 1 cm proximal to 2 cm distal of the
EGJ. Histological analysis indicates that the cardiac gland is present with a
high degree of frequency between 1-2 cm to the gastric side and 1-2 cm to the
esophageal side of the EGJ, which means that this zone can be considered as
neither the stomach nor the esophagus but rather as a third zone known as the
'EGJ zone'. It has been suggested that there are multiple causes for development
of adenocarcinoma in the EGJ zone. The TNM Classification of Malignant Tumours
7th Edition considers EGJ adenocarcinoma (EGJAC) occurring in the EGJ zone to be
a part of esophageal adenocarcinoma (EAC). However, recent studies have indicated
that EGJAC behaves differently from EAC and gastric carcinoma. Barrett's
esophagus is now considered an important factor in the etiology of EGJAC, but, as
yet, no studies have elucidated the differences between cancer arising from short
segment Barrett's esophagus and cancer of the gastric cardia. Thus, there is
currently no clinical relevance to subdivision of adenocarcinoma in the EGJ zone
into above or below the EGJ line.
PMID- 28425657
TI - Different time trend and management of esophagogastric junction adenocarcinoma in
three Asian countries.
AB - Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western
countries. However, in Asian countries, data on the incidence of EGJ
adenocarcinoma are evidently lacking. In the present review, we focus on the
current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan,
Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to
be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong
Kong. However, the number of cases in these countries is comparatively low
compared with Western countries. A reason for the reported difference in the
incidence and time trend of EGJ adenocarcinoma among the three countries may be
explained by two distinct etiologies: one arising from chronic gastritis similar
to distal gastric cancer, and the other related to gastroesophageal reflux
disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma.
This review also shows that there are several concerns in clinical practice for
EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been
detected at a stage not amenable to endoscopic resection. In Japan, histological
curability criteria for endoscopic resection cases have not been established. We
suggest that an international collaborative study using the same definition of
EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of
these cancers but also for improving the clinical outcome of these patients.
PMID- 28425658
TI - Endoscopic management of acute cholangitis as a result of common bile duct
stones.
AB - Acute cholangitis is infectious disease of the biliary system and potentially can
cause significant morbidity and mortality. With advances in intensive care,
antibiotic therapy advances and endoscopic and other modalities of biliary
drainage, mortality rates have significantly come down of late. Although most
cases respond to antibiotics alone, definitive therapy is required later in most
of the patients. Increased biliary pressure leads to biliovenous reflux of
bacteria and purulent bile into the circulation leading to systemic inflammation
and sepsis with subsequent organ dysfunction. Biliary decompression increases
antibiotic penetration in bile. Therefore, patients with high-risk factors and
organ dysfunction require early and urgent biliary drainage, respectively, as
they are unlikely to respond with antibiotics alone. Biliary decompression is
best achieved by endoscopic retrograde cholangiopancreatography (ERCP) compared
to percutaneous and surgical decompression. ERCP can be technically difficult and
sometimes unsuccessful especially in patients with altered anatomy and upper
gastrointestinal obstruction. Earlier percutaneous transhepatic biliary drainage
(PTBD) and surgery were the only viable options in those patients. PTBD requires
a dilated biliary system, is more invasive and cannot achieve ductal clearance in
cholangitis as a result of choledocholithiasis, whereas surgery is associated
with high morbidity and mortality. Advances in therapeutic endoscopy such as
balloon enteroscopy-guided biliary drainage or endoscopic ultrasound guided
biliary drainage have added new dimensions to endoscopic management of acute
cholangitis as a result of choledocholithiasis obviating the need for more
invasive procedures.
PMID- 28425660
TI - Endoscopic submucosal dissection for large colorectal neoplasms.
AB - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) for colorectal
neoplasms (CRN) of >50 mm is considered technically difficult. The ITknife nanoTM
was developed specifically for ESD of CRN and esophageal superficial neoplasms;
however, only limited data are available regarding its use in this procedure.
Here we assessed the safety and efficacy of ESD using the ITknife nanoTM for
large CRN (>50 mm). METHODS: We carried out a retrospective study, including
consecutive patients with CRN larger than 50 mm that were treated by ESD between
September 2002 and August 2016 at our institution. To clarify features of the
ITknife nanoTM and to assess its safety and efficacy, we compared en
bloc/curative resection rates, complications, and resection speed between ESD
done using the Dual knifeTM with and without the ITknife nanoTM. RESULTS: We
analyzed a total of 177 ESD-treated large CRN (median tumor size, 61 mm). Among
the 133 CRN treated by ESD using the ITknife nanoTM, en bloc and curative
resection rates were 96.2% and 80.5%, respectively. Perforation occurred in eight
cases (6.0%) and delayed bleeding in four cases (3.0%). All complications were
endoscopically managed. Resection speed was significantly faster for ESD using
the ITknife nanoTM (25.3 mm2 /min) compared to using the Dual knifeTM only (19.9
mm2 /min; P = 0.02). CONCLUSIONS: Use of the ITknife nanoTM for ESD treatment of
large CRN (>50 mm) is feasible and may contribute to reduced procedure times.
Further controlled studies are needed to confirm these findings.
PMID- 28425661
TI - Preface.
PMID- 28425662
TI - Feasibility of colorectal endoscopic submucosal dissection (ESD) carried out by
endoscopists with no or little experience in gastric ESD.
AB - BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) is
recommended to be carried out only by endoscopists with sufficient experience in
gastric ESD. However, early gastric carcinoma is less common in Western countries
than in Japan, and endoscopic maneuverability differs between the stomach and
colorectum. We assessed the feasibility of colorectal ESD carried out by
endoscopists with no or little experience in gastric ESD. METHODS: We analyzed en
bloc resection, R0 resection and perforation rates in 180 consecutive colorectal
ESD carried out by three endoscopists who had no or <5 cases of experience in
gastric ESD. We also identified factors associated with R0 resection failure.
RESULTS: Overall en bloc and R0 resection rates were 93.3% (168/180) and 82.2%
(148/180), respectively. All 11 cases with perforation were treated
endoscopically. Dividing 180 cases into three learning phases (early, middle, or
late phases), the en bloc and R0 resection rates increased from 88.3% and 75.0%
in the early phase to 98.3% and 88.3% in the late phase, respectively.
Perforation rate also improved from 10.0% to 3.3%. Factors associated with R0
resection failure were location at junctions (odds ratio: 6.8, 95% CI: 1.9-27.5),
preoperative factors reflecting fibrosis (5.8, 1.9-19.0), and late phase (0.2,
0.1-0.7). CONCLUSION: Endoscopists without experience in gastric ESD carried out
colorectal ESD safely. In the early and middle phases (<=40 cases), they should
treat mainly rectal lesions but may also resect lesions in the colon avoiding
flexures. Lesions located at junctions and those with preoperative factors
reflecting fibrosis should be resected after completing 40 procedures.
PMID- 28425663
TI - Management of acute cholangitis as a result of occlusion from a self-expandable
metallic stent in patients with malignant distal and hilar biliary obstructions.
AB - Acute cholangitis as a result of common bile duct stones can be managed; however,
cholangitis caused by occlusion with a biliary self-expandable metallic stent
(SEMS) in patients with an unresectable malignant biliary obstruction has not
been fully discussed. The acute cholangitis clinical guidelines (Tokyo Guidelines
2013) recommend following the same procedure as that used for cholangitis;
however, the patient's condition, including performance status, tumor extension
or staging, and prognosis must be considered. Most physicians manage cholangitis
from a SEMS occlusion using a two-step procedure. They insert endoscopic drainage
with a plastic stent or insert a nasobiliary drainage tube, which does not
exacerbate sepsis. Addition or replacement of a biliary SEMS is required in many
cases depending on the cause of the occlusion. Tumor ingrowth through the stent
mesh is common in uncovered SEMS and requires placement of another stent in an in
stent method. However, covered SEMS tends to be occluded by sludge, so it must be
replaced because of the bacterial biofilm that forms on the covering membrane.
The location of the biliary stricture (hilar or distal) should also be
considered. Strategies for managing cholangitis as a result of occlusion by a
biliary SEMS remain controversial, so prospective clinical trials are needed.
PMID- 28425664
TI - Endoscopic diagnosis of subsquamous invasion of adenocarcinoma in short-segment
Barrett's esophagus.
PMID- 28425665
TI - Standardization of endoscopic resection for colorectal tumors larger than 10 mm
in diameter.
AB - Currently, several endoscopic resection (ER) methods for colorectal tumors are
available, including polypectomy, conventional endoscopic mucosal resection
(EMR), endoscopic submucosal dissection (ESD), and modified ER. In the present
review, we mainly focus on the current status of ER for colorectal tumors as well
as the report from the Endoscopic Forum Japan (EFJ) 2016, which was held in Tokyo
in August 2016. The proposed ER methods for colorectal tumors larger than 10 mm
in diameter are as follows. (i) Pedunculated-type tumor is an indication for
polypectomy, regardless of size. (ii) Non-pedunculated-type tumor larger than 20
mm in diameter is an indication for ESD in which en bloc resection using
conventional EMR is difficult or impossible. (iii) Non-pedunculated-type tumor
from 10 mm to 20 mm in diameter is an indication for conventional EMR. However,
ESD or modified ER methods are acceptable according to the procedure and the
condition of the tumor.
PMID- 28425666
TI - Endoscopic management of acute cholangitis according to the TG13.
AB - The Tokyo Guidelines 2013 (TG13) recommend that endoscopic drainage should be the
first-choice treatment for biliary decompression in patients with acute
cholangitis. Timing of biliary drainage for acute cholangitis should be based on
the severity of the disease. For patients with severe acute cholangitis,
appropriate organ support and urgent biliary drainage are needed. For patients
with moderate acute cholangitis, early biliary drainage is needed. For patients
with mild acute cholangitis, biliary drainage is needed when initial treatment
such as antimicrobial therapy is ineffective. There are three methods of biliary
drainage: endoscopic drainage, percutaneous transhepatic drainage, and surgical
drainage. Endoscopic drainage is less invasive than the other two drainage
methods. The drainage method (endoscopic nasobiliary drainage and stenting)
depends on the endoscopist's preference but endoscopic sphincterotomy should be
selected rather than endoscopic papillary balloon dilation from the aspect of
procedure-related complications. In the TG13, balloon enteroscopy-assisted and
endoscopic ultrasound-guided biliary drainages have been newly added as specific
drainage methods. Recent studies have demonstrated their usefulness and safety.
These drainage methods will become more widespread in the future.
PMID- 28425667
TI - Soft Multifunctional Composites and Emulsions with Liquid Metals.
AB - Binary mixtures of liquid metal (LM) or low-melting-point alloy (LMPA) in an
elastomeric or fluidic carrier medium can exhibit unique combinations of
electrical, thermal, and mechanical properties. This emerging class of soft
multifunctional composites have potential applications in wearable computing, bio
inspired robotics, and shape-programmable architectures. The dispersion phase can
range from dilute droplets to connected networks that support electrical
conductivity. In contrast to deterministically patterned LM microfluidics, LMPA-
and LM-embedded elastomer (LMEE) composites are statistically homogenous and
exhibit effective bulk properties. Eutectic Ga-In (EGaIn) and Ga-In-Sn
(Galinstan) alloys are typically used due to their high conductivity, low
viscosity, negligible nontoxicity, and ability to wet to nonmetallic materials.
Because they are liquid-phase, these alloys can alter the electrical and thermal
properties of the composite while preserving the mechanics of the surrounding
medium. For composites with LMPA inclusions (e.g., Field's metal, Pb-based
solder), mechanical rigidity can be actively tuned with external heating or
electrical activation. This progress report, reviews recent experimental and
theoretical studies of this emerging class of soft material architectures and
identifies current technical challenges and opportunities for further
advancement.
PMID- 28425668
TI - Pectin, Hemicellulose, or Lignin? Impact of the Biowaste Source on the
Performance of Hard Carbons for Sodium-Ion Batteries.
AB - Hard carbons are currently the most widely used negative electrode materials in
Na-ion batteries. This is due to their promising electrochemical performance with
capacities of 200-300 mAh g-1 and stable long-term cycling. However, an abundant
and cheap carbon source is necessary in order to comply with the low-cost
philosophy of Na-ion technology. Many biological or waste materials have been
used to synthesize hard carbons but the impact of the precursors on the final
properties of the anode material is not fully understood. In this study the
impact of the biomass source on the structural and electrochemical properties of
hard carbons is unraveled by using different, representative types of biomass as
examples. The systematic structural and electrochemical investigation of hard
carbons derived from different sources-namely corncobs, peanut shells, and waste
apples, which are representative of hemicellulose-, lignin- and pectin-rich
biomass, respectively-enables understanding and interlinking of the structural
and electrochemical properties.
PMID- 28425669
TI - Dissolving Lignin in Water through Enzymatic Sulfation with Aryl
Sulfotransferase.
AB - We introduce the concept of using site-specific sulfation of various lignins for
increasing their aqueous solubility and thereby their processability. Using p
nitrophenylsulfate as a sulfate source and an aryl sulfotransferase enzyme as
catalyst, lignins are easily sulfated at ambient conditions. We demonstrate the
specific sulfation of phenolic hydroxyl groups on five different lignins: Indulin
AT (Kraft softwood), Protobind 1000 (mixed wheat straw/Sarkanda grass soda) and
three organosolv lignins. The reaction proceeds smoothly and the increase in
solubility is visible to the naked eye. We then examine the reaction kinetics,
and show that these are easily monitored qualitatively and quantitatively using
UV/Vis spectroscopy. The UV/Vis results are validated with 31 P NMR spectroscopy
of the lignin phenol groups after derivatization with phosphorylation reagent II.
In general, the results are more significant with organosolv lignins, as Kraft
and soda lignins are produced from aqueous lignocellulose extraction processes.
PMID- 28425670
TI - Electroencephalographic patterns of lithium poisoning: a study of the
effect/concentration relationships in the rat.
AB - OBJECTIVES: Lithium overdose may result in encephalopathy and
electroencephalographic abnormalities. Three poisoning patterns have been
identified based on the ingested dose, previous treatment duration and renal
function. Whether the severity of lithium-induced encephalopathy depends on the
poisoning pattern has not been established. We designed a rat study to
investigate lithium-induced encephalopathy and correlate its severity to plasma,
erythrocyte, cerebrospinal fluid and brain lithium concentrations previously
determined in rat models mimicking human poisoning patterns. METHODS: Lithium
induced encephalopathy was assessed and scored using continuous
electroencephalography. RESULTS: We demonstrated that lithium overdose was
consistently responsible for encephalopathy, the severity of which depended on
the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy
which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post
injection. Acute-on-chronically poisoned rats developed persistent and slightly
fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically
poisoned rats developed rapid-onset but gradually increasing life-threatening
encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of
the acute-on-chronically and 57% of the chronically lithium-poisoned rats
developed seizures. The relationships between encephalopathy severity and lithium
concentrations fitted a sigmoidal Emax model based on cerebrospinal fluid
concentrations in acute poisoning and brain concentrations in acute-on-chronic
poisoning. In chronic poisoning, worsening of encephalopathy paralleled the
increase in plasma lithium concentrations. CONCLUSIONS: The severity of lithium
induced encephalopathy is dependent on the poisoning pattern, which was
previously shown to determine lithium accumulation in the brain. Our data support
the proposition that electroencephalography is a sensitive tool for scoring
lithium-related neurotoxicity.
PMID- 28425672
TI - Evaluating therapeutic effect on WOMAC subscales in osteoarthritis RCTs: When
model choice matters.
AB - RATIONALE, AIMS, AND OBJECTIVES: The study aimed at developing a method for
modelling the Western Ontario and McMaster Universities index (WOMAC), accounting
for correlation between its subscales and for heterogeneity of treatment effect
(HTE), using data from 2 twin trials on knee osteoarthritis. METHOD: Two
randomized, double-blind, placebo-controlled clinical trials (twin trials).
Studies aimed at investigating the effectiveness of a pharmacological treatment
on clinical outcomes of knee osteoarthritis, measured using WOMAC index. To take
into account that the WOMAC subscales are correlated and skewed, we proposed and
compared multivariate gamma and Gaussian approaches with latent variable
capturing correlation between outcomes. Besides the latent term, the interaction
between the latent term and treatment, accounting for HTE, was further estimated.
RESULTS: Modelling the subscales by using a gamma approach accounting for
skewness of data, we found out different results compared with Gaussian models.
The main difference regarded the latent variable interacting with treatment
(accounting for unobserved heterogeneity), which is not significant for the
Gaussian approach (P value = .102) and significant in the gamma model (P value <
.002). Thus, indicating that unobserved covariates affect treatment's
performance. Additionally, plotting the observed and the estimated values of
WOMAC index of the Gaussian and gamma models, we showed that, compared with the
Gaussian, the gamma one best fits the data, especially among poor responders.
CONCLUSION: Multivariate gamma approach accounting for correlation between
outcomes and for HTE has been demonstrated to be more suitable to model WOMAC
subscales and to provide more information on effect of therapy.
PMID- 28425673
TI - Reply.
PMID- 28425671
TI - Activity-Based Probes for HECT E3 Ubiquitin Ligases.
AB - Activity-based probes (ABPs) have been used to dissect the biochemical/structural
properties and cellular functions of deubiquitinases. However, their utility in
studying cysteine-based E3 ubiquitin ligases has been limited. In this study, we
evaluate the use of ubiquitin-ABPs (Ub-VME and Ub-PA) and a novel set of E2-Ub
ABPs on a panel of HECT E3 ubiquitin ligases. Our in vitro data show that
ubiquitin-ABPs can label HECT domains. We also provide the first evidence that,
in addition to the RBR E3 ubiquitin ligase Parkin, E2-Ub-ABPs can also label the
catalytic HECT domains of NEDD4, UBE3C, and HECTD1. Importantly, the endogenous
proteasomal E3 ligase UBE3C was also successfully labelled by Ub-PA and His
UBE2D2-Ub-ABP in lysate of cells grown under basal conditions. Our findings
provide novel insights into the use of ABPs for the study of HECT E3 ubiquitin
ligases.
PMID- 28425674
TI - Comment on "Early Innovative Immersion: A Course for Pre-Medical Professions
Students Using Point-of-Care Ultrasound".
PMID- 28425675
TI - Reply.
PMID- 28425676
TI - Erratum.
PMID- 28425677
TI - Web alert: Microbial dehalogenation: An annotated selection of World Wide Web
sites relevant to the topics in environmental microbiology.
PMID- 28425678
TI - Thinking about quantity: the intertwined development of spatial and numerical
cognition.
PMID- 28425679
TI - Soft interactions and volume exclusion by polymeric crowders can stabilize or
destabilize transient structure in disordered proteins depending on polymer
concentration.
AB - The effects of macromolecular crowding on the transient structure of
intrinsically disordered proteins is not well-understood. Crowding by biological
molecules inside cells could modulate transient structure and alter IDP function.
Volume exclusion theory and observations of structured proteins suggest that IDP
transient structure would be stabilized by macromolecular crowding. Amide
hydrogen exchange (HX) of IDPs in highly concentrated polymer solutions would
provide valuable insights into IDP transient structure under crowded conditions.
Here, we have used mass spectrometry to measure HX by a transiently helical
random coil domain of the activator of thyroid and retinoid receptor (ACTR) in
solutions containing 300 g L-1 and 400 g L-1 of Ficoll, a synthetic
polysaccharide, using a recently-developed strong cation exchange-based cleanup
method [Rusinga, et al., Anal Chem 2017;89:1275-1282]. Transiently helical
regions of ACTR exchanged faster in 300 g L-1 Ficoll than in dilute buffer. In
contrast, one transient helix exchanged more slowly in 400 g L-1 Ficoll.
Nonspecific interactions destabilize ACTR helicity in 300 g L-1 Ficoll because
ACTR engages with the Ficoll polymer mesh. In contrast, 400 g L-1 Ficoll is a
semi-dilute solution where ACTR cannot engage the Ficoll mesh. At this higher
concentration, volume exclusion stabilizes ACTR helicity because ACTR is
compacted in interstitial spaces between Ficoll molecules. Our results suggest
that the interplay between nonspecific interactions and volume exclusion in
different cellular compartments could modulate IDP function by altering the
stability of IDP transient structures. Proteins 2017; 85:1468-1479. (c) 2017
Wiley Periodicals, Inc.
PMID- 28425680
TI - Adaptation to health states: Sick yet better off?
AB - Healthcare funding decisions in the UK rely on health state valuations of the
general public. However, it has been shown that there is disparity between the
valuation of the impact of hypothetical conditions on health and the reported
health by those experiencing them. Patients' adaptation to health states is among
the most common explanations for this discrepancy. Being diagnosed with a disease
appears to affect individual perception of health over time so that better
subjective health may be reported over a disease trajectory. This paper examines
adaptation to health states using a longitudinal dataset. We use four waves of
the British Cohort Study (BCS70), which tracks a sample of British individuals
since birth in 1970 and contains information on self-assessed health (SAH),
morbidity, and socioeconomic characteristics. We implement a dynamic ordered
probit model controlling for health state dependence. Results are supportive of
the existence of adaptation: Time since diagnosis has a positive impact on SAH.
Moreover, adaptation happens over relatively long durations. We do not find
significant results proving different adaptation paths for patients reporting
prior better SAH. The analysis by specific conditions generally supports the
existence of adaptation, but results are statistically significant only for a
subset of conditions.
PMID- 28425681
TI - Schedules of Controlled Substances: Temporary Placement of Six Synthetic
Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB
FUBINACA) into Schedule I. Temporary Scheduling Order.
AB - The Administrator of the Drug Enforcement Administration is issuing this
temporary scheduling order to schedule six synthetic cannabinoids: methyl 2-(1-(5
fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [5F-ADB; 5F-MDMB
PINACA]; methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3
methylbutanoate [5F-AMB]; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3
carboxamide [5F-APINACA, 5F-AKB48]; N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1
(4-fluorobenzyl)-1H-indazole-3-carboxamide [ADB-FUBINACA]; methyl 2-(1
(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-CHMICA,
MMB-CHMINACA] and methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3
dimethylbutanoate [MDMB-FUBINACA], and their optical, positional, and geometric
isomers, salts, and salts of isomers into schedule I pursuant to the temporary
scheduling provisions of the Controlled Substances Act. This action is based on a
finding by the Administrator that the placement of these synthetic cannabinoids
into schedule I of the Controlled Substances Act is necessary to avoid an
imminent hazard to the public safety. As a result of this order, the regulatory
controls and administrative, civil, and criminal sanctions applicable to schedule
I controlled substances will be imposed on persons who handle (manufacture,
distribute, reverse distribute, import, export, engage in research, conduct
instructional activities or chemical analysis, or possess), or propose to handle,
5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA or MDMB-FUBINACA.
PMID- 28425682
TI - Mild acute biliary pancreatitis: the timing of cholecystectomy should not exceed
index admission.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) to treat mild biliary acute
pancreatitis (MBAP) during index admission is recommended. However, the optimal
surgical timing is controversial, considering that patients are actually often
discharged from hospital and readmitted for elective cholecystectomy. Moreover,
previous studies showed an uneven patients' stratification for pancreatitis
severity. The aim of this study was to determine the outcome of patients
homogenously categorizedfor MBAP according to the newest pancreatitis
classifications, undergoing cholecystectomy with different timing. METHODS: We
retrospectively identified all patients undergoing cholecystectomy from 2008 to
2015 for MBAP, according to the 2012 Revision of the Atlanta Classification and
the Determinant-Based Classification of Acute Pancreatitis, and stratified them
in two groups: index cholecystectomy (IC) and interval-delayed cholecystectomy
(IDC, after at least 4 weeks). RESULTS: One hundred and three patients were
analyzed. IC was performed in 40 patients (38.8%) while IDC in 63 patients
(61.2%). The two groups were similar in comorbidities and pancreatitis severity
at admission. There were no differences for conversion rate, operation length,
total length of hospitalization and overall complication rates. However, IDC
patients had a 33.3% rate of re-hospitalization for recurrent biliary-pancreatic
events while waiting for the elective procedure and showed a higher rate of acute
cholecystitis at histological diagnosis than IC (11.1% vs. 0%, P=0.041).
CONCLUSIONS: Among patients affected by MBAP, homogenously assessed following the
new acute pancreatitis severity scores, the performance of cholecystectomy during
the index admission is the best treatment option in order to avoid further
undesired hospitalizations for recurrent biliary/pancreatic events while waiting
for surgery.
PMID- 28425683
TI - Preservation of duodenal passage as a determinant of short- and long-term quality
of life in gastric cancer patients after total gastrectomy.
AB - BACKGROUND: The aim of this prospective study was to compare subjective and
objective quality of life (QoL) of gastric cancer patients after total
gastrectomy with and without preservation of the duodenal passage during short-
and long-term follow-up. METHODS: The study included 68 patients, among them 37
(54%) persons subjected to total gastrectomy with Roux-Y reconstruction (R-Y
group) and 31 (46%) individuals in whom gastrectomy was followed by formation of
Henley-Longmire loop (H-L group). Subjective and objective QoL was determined 1
and 10 years postsurgery. During each visit, subjective QoL was determined with
EORTC QLQ-C30 questionnaire, along with markers of nutritional status and self
reported incidence of symptoms specific to postgastrectomy syndrome. RESULTS: The
two groups did not differ significantly in terms of their subjective QoL and
markers of nutritional status at 1 and 10 years postsurgery, and none of these
parameters underwent significant changes between the first and second evaluation.
Patients from R-Y group reported subjective weight loss significantly more often
during both visits, and individuals from H-L group significantly more often
complained on postprandial diarrhea during long-term follow-up. Moreover, both
groups showed an increase in the incidence of postprandial vomiting between the
first and second evaluation. CONCLUSIONS: QoL of gastric cancer patients
subjected to total gastrectomy stabilizes at relatively high level within a year
from the surgery. Preservation of the duodenal passage does not exert a
beneficial effect on both objective and subjective QoL after total gastrectomy.
PMID- 28425684
TI - Single versus two-operator endoscopic biliary cannulation technique: a
multicenter matched-case analysis.
AB - BACKGROUND: The aim of this study was to compare the outcomes of physician
controlled, using both long and short endoscopic-retrograde
cholangiopancreatography wire systems, and assistant-controlled guide-wire
biliary cannulation techniques, and to perform a literature review on this topic.
METHODS: The endoscopic databases of three Endoscopic Centers were reviewed to
identify all consecutive patients with an intact papilla who, between July 2013
and December 2014, underwent an endoscopic-retrograde-cholangiopancreatography. A
total of 240 patients (80 for each group) were matched 1:1, by gender, age and
indications for procedure and were included in the analysis. All articles of
physician-controlled vs. assistant-controlled guide-wire biliary cannulation
techniques, were extracted up to December 2016, and included in the review.
RESULTS: There were no statistically significant differences in primary and final
(using rescue technique) cannulation rate between the three groups. The mean
primary cannulation time and overall cannulation time were shorter in the two
groups of physician-controlled guide-wire compared to the assistant-controlled
guide-wire group, but the difference was not statistically significant. The total
procedure time did not differ significantly between the three groups, but the
physician-controlled guide-wire using short wire system was associated with a
trend toward a shorter time compared to the other two techniques. There were no
statistically significant differences in complication rates between the three
groups. Three pertinent articles were included in the review. The mean procedure
success and complication rates were 92% and 7%, respectively. CONCLUSIONS: The
literature review and our results show that all these techniques have equally
efficacy and safety for guide-wire cannulation.
PMID- 28425685
TI - Is T4 colon cancer still an absolute contraindication to laparoscopic surgery?
AB - BACKGROUND: Laparoscopic surgery is widely accepted for colon cancer resection.
However, T4 colon cancers have been considered an absolute contraindication to
laparoscopic resection. The aim of this study is to evaluate if laparoscopy
should still be considered an absolute contraindication to T4 colon cancer, based
on a monocenter series recorded in a prospective database. METHODS: Of 77
patients undergoing elective resection for T4 colon cancer between 2004 and 2015,
39 were performed laparoscopically and were compared to 38 having undergone open
resection. RESULTS: Patient age and American Society of Anesthesiologists score
were comparable. Eleven patients initially treated laparoscopically were
converted to an open approach (28.2%). There were no statistically significant
differences between laparoscopy vs. open concerning tumor stage, R0 resections,
operative time, metastatic rate, local recurrence rate or hospital stay.
Laparoscopic surgery was associated with less postoperative complications than
open surgery (25.6% vs. 52.6%; P=0.020). No statistically significant difference
was found with regards to the 3-year overall, tumor-specific and disease-free
survivals. CONCLUSIONS: As there were less postoperative complications, while
tumor stage, operative time, hospital stay, R0 resection and survival rates after
laparoscopic resection for T4 colonic cancer were not statistically significantly
different compared to open surgery, T4 colon cancers are no longer an absolute
contraindication to laparoscopic resection in our hospital.
PMID- 28425686
TI - If time matters: a multicenter review of minimally-invasive hernia repair in 7176
cases.
AB - BACKGROUND: In endoscopic hernia repair totally extraperitoneal approach (TEP)
and transabdominal preperitoneal approach (TAPP) are seen as equivalent surgical
techniques in quality, but not in procedure-time. METHODS: We compared the two
most common procedures in endoscopic hernia surgery. Focusing on the duration of
the surgical procedure, we analyzed 7176 endoscopic hernia operations in 25
hospitals retrospectively and compared it to the literature. RESULTS: In our
study TEP (N.=2799) took on average 59 minutes, TAPP (N.=4377) took 67.5 minutes,
thus with a significant difference (P=0.043). In high volume centres this
difference was even bigger. As there are few consistent advantages of one of the
procedures in general, the procedure' s duration becomes more important.
CONCLUSIONS: If time is the main reason, the TEP procedure takes on average 8.5
minutes less time, so it can be more cost-effective.
PMID- 28425687
TI - Patient Protection and Affordable Care Act; Market Stabilization. Final rule.
AB - This rule finalizes changes that will help stabilize the individual and small
group markets and affirm the traditional role of State regulators. This final
rule amends standards relating to special enrollment periods, guaranteed
availability, and the timing of the annual open enrollment period in
theindividual market for the 2018 plan year; standards related to network
adequacy and essential community providers for qualified health plans; andthe
rules around actuarial value requirements.
PMID- 28425688
TI - Pediatric epilepsy and psychiatric comorbidity: preliminary observational data
from a prospective study.
AB - BACKGROUND: Several studies have confirmed psychiatric comorbidity and a worse
quality of life in children with epilepsy, but the clinical assessment and
monitoring of these patients often pays insufficient attention to their
psychological aspects alongside their neurological issues. The present study aims
to describe the distribution of psychopathologies and their clinical evolution
over 18 months in a sample of children followed up since the onset of their
epilepsy. METHODS: After being diagnosed with epilepsy, 49 subjects (age 4-18y)
were followed up with psychiatric and psychological assessments based on the use
of dimensional and categorical psychometric tools. RESULTS: Baseline data (T0)
showed a high psychiatric comorbidity in epileptic children, with a prevalence of
anxious-depressive disorders and attention deficit hyperactivity disorder (ADHD).
Specifically, generalized epilepsy, antiepileptic drug intake and more frequent
seizures were associated with externalizing problems, while focal epilepsy was
linked with anxiety disorders. The follow-up at 18 months revealed that about 90%
of patients had achieved a reduction in the frequency and duration of their
seizures, but their psychopathological assessment remained virtually unchanged.
The patients' psychological issues had warranted psychotherapy in 43% of cases.
CONCLUSIONS: When children or adolescents are diagnosed with epilepsy, their
psychopathological profile should be investigated and monitored over time.
Psychotherapy and/or psychopharmacological treatments should be offered to
pediatric patients with epilepsy who suffer from emotional-behavioral disorders.
PMID- 28425689
TI - Normal values of creatine kinase and of MB-creatine kinase at birth in healthy
babies.
AB - BACKGROUND: Today, few studies have been accomplished in order to determine serum
creatine kinase (CK) activity in newborns by considering small groups of babies
and without taking into account gestational age (GA) differences. Some authors
have demonstrated that neonatal CK activity value at birth is higher than the
normal range of CK activity considering for adults or older children. The
objective of this study is to assess normal values of CK and MB-CK in neonatal
blood, according to babies' GA. METHODS: We retrieved the clinical files of 140
babies admitted into Siena Hospital NICU in a 2-years period, when CK was
assessed routinely to all babies at birth. We selected files from 114 newborns
and we divided the cohort into group A (non-stressed; n=41) and group B
(stressed; n=73) on the basis of Apgar score and signs of neurological lesions.
We compared CK and MB-CK values in the two groups according to GA. RESULTS: Mean
CK value of the 41 non-stressed babies' samples: 413 IU/L (232 SD). CK
significantly increases with GA. No differences are present in total CK activity
between stressed vs non-stressed babies; but a significant difference appears in
these two groups for MB-CK (mean values: 456 vs 175 IU/L). CONCLUSIONS: This is
the first study that compares CK and MB-CK values at birth according to the GA of
the babies. CK values increase with GA, and stressed babies have higher MB-CK
values than the non-stressed babies. These reference values are important for
clinical practice.
PMID- 28425690
TI - What's new with common genetic skin disorders?
AB - Familiar genetic disorders such as neurofibromatosis type I (NF1), tuberous
sclerosis complex (TSC), oculocutaneous albinism (OCA), basal cell nevus syndrome
(BCNS), incontinentia pigmenti, ichthyosis, and epidermolysis bullosa (EB) have
prominent, cutaneous manifestations. This review describes recent advances in
knowledge concerning the pathophysiology, diagnosis, and treatment of these skin
features. Specifically, clinical diagnostic criteria for incontinentia pigmenti,
ichthyosis, and tuberous sclerosis have been updated. Additionally, there have
been considerable advancements in the technology used in the molecular diagnoses
of these conditions. In the case of TSC, the discovery that a portion of TSC
mutations are missed due to mosaicism is driving the development of new
diagnostic methods. Also, scientists are also seeking minimally invasive methods
of genetic diagnosis, as in the case of using hair follicles to diagnose
autosomal recessive congenital ichythosis (ARCI). Finally, there are innovative
targeted medical therapies being developed that serve as promising tools in the
care of patients afflicted with conditions including ichthyosis and EB.
PMID- 28425692
TI - Antitrust Law--Hospital Mergers--Third Circuit Clarifies Geographic Market
Definition and Raises Bar for Efficiencies Defense.
PMID- 28425691
TI - Health implications of new-age technologies: a systematic review.
AB - INTRODUCTION: New-age technologies are ubiquitous in the lives of adolescents.
Recent trends in media use suggest that adolescents are spending more time than
ever engaging with technologies, and are able to do so in virtually all settings
at any time. Given that new-age technologies are so heavily integrated within the
daily life of adolescents, the health risks and benefits they offer must be
closely examined. EVIDENCE ACQUISITION: In this systematic review, we present
recent literature related to the implications of new-age technologies on
adolescent health. A total of 94 articles published since 2006 were collected
using PubMed and Google Scholar on the most popular new-age technologies among
adolescents: the internet, television, cell phones, and video games. EVIDENCE
SYNTHESIS: The current body of research highlights several health risks related
to these technologies. Nearly all have the potential for addiction, which can
result in other symptoms and impair one's daily life. Excessive use can affect
several components of health, such as quality of sleep, body composition, and
mental well-being, and certain practices (viewing pornography, sexting) can lead
to risky sexual behaviors. However, the technologies discussed in the present
review also have tremendous potential to promote adolescent health. CONCLUSIONS:
Pediatricians must educate parents and patients on how to safely use technology
to minimize the potentially harmful outcomes.
PMID- 28425693
TI - Supporting Higher Education for People with Disabilities.
PMID- 28425694
TI - State Newborn Health Screening Policies.
PMID- 28425695
TI - Reduced Graphene Oxide-Containing Smart Hydrogels with Excellent Electro-Response
and Mechanical Properties for Soft Actuators.
AB - A novel reduced graphene oxide/poly(2-acrylamido-2-methylpropanesulfonic acid-co
acrylamide) (rGO/poly(AMPS-co-AAm)) nanocomposite hydrogel that possesses
excellent electro-response and mechanical properties has been successfully
developed. The rGO nanosheets that homogeneously dispersed in the hydrogels could
provide prominent conductive platforms for promoting the ion transport inside the
hydrogels to generate significant osmotic pressure between the outside and inside
of such nanocomposite hydrogels. Thus, the electro-responsive rate and degree of
the hydrogel for both deswelling and bending performances become rapid and
remarkable. Moreover, the enhanced mechanical properties including both the
tensile strength and compressive strength of rGO/poly(AMPS-co-AAm) hydrogels are
improved by the hydrogen-bond interactions between the rGO nanosheets and polymer
chains, which could dissipate the strain energy in the polymeric networks of the
hydrogels. The proposed rGO/poly(AMPS-co-AAm) nanocomposite hydrogels with
improved mechanical properties exhibit rapid, significant, and reversible electro
response, which show great potential for developing remotely controlled electro
responsive hydrogel systems, such as smart actuators and soft manipulators.
PMID- 28425696
TI - Granadilla-Inspired Structure Design for Conversion/Alloy-Reaction Electrode with
Integrated Lithium Storage Behaviors.
AB - Conversion/alloy-reaction electrode materials promise much higher energy density
than the commonly used ones based on intercalation chemistries. However, the low
electronic conductivity and, specially, the large volume expansion upon
lithiation hinder their practical applications. Here, for the first time, a
unique granadilla-inspired structure was designed to prepare the conversion/alloy
reaction anode of carbon coated tin/calcium tin oxide (C@void@Sn/CaSnO3) ternary
composite. The granadilla-inspired structure ensures the intimate contact between
the Sn/CaSnO3 nanoparticles and the carbon matrix, providing not only conductive
networks for electron transport and a short distance for Li+ diffusion but also
effective space for the electrode volume expansion toward conversion/alloy
reaction. Moreover, the unique structure possesses abundant solid-solid
interfaces between the three components as well as solid-liquid interfaces
between nanoparticles and electrolyte, contributing to a large percent (58%) of
interfacial charge (thus capacity). The integration of alloy-reaction, conversion
reaction, and interfacial lithium storage endows the hybrid electrode with a high
capacity and long cycling life, holding great promise for next-generation high
capacity lithium-ion batteries.
PMID- 28425698
TI - Dispersion-Assembly Approach to Synthesize Three-Dimensional Graphene/Polymer
Composite Aerogel as a Powerful Organic Cathode for Rechargeable Li and Na
Batteries.
AB - Polymer cathode materials are promising alternatives to inorganic counterparts
for both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) due to
their high theoretical capacity, adjustable molecular structure, and strong
adaptability to different counterions in batteries, etc. However, they suffer
from poor practical capacity and low rate capability because of their
intrinsically poor conductivity. Herein, we report the synthesis of self
assembled graphene/poly(anthraquinonyl sufide) (PAQS) composite aerogel (GPA)
with efficient integration of a three-dimensional (3D) graphene framework with
electroactive PAQS particles via a novel dispersion-assembly strategy which can
be used as a free-standing flexible cathode upon mechanical pressing. The entire
GPA cathode can deliver the highest capacity of 156 mAh g-1 at 0.1 C (1 C = 225
mAh g-1) with an ultrahigh utilization (94.9%) of PAQS and exhibits an excellent
rate performance with 102 mAh g-1 at 20 C in LIBs. Furthermore, the flexible GPA
film was also tested as cathode for SIBs and demonstrated a high-rate capability
with 72 mAh g-1 at 5 C and an ultralong cycling stability (71.4% capacity
retention after 1000 cycles at 0.5 C) which has rarely been achieved before. Such
excellent electrochemical performance of GPA as cathode for both LIBs and SIBs
could be ascribed to the fast redox kinetics and electron transportation within
GPA, resulting from the interconnected conductive framework of graphene and the
intimate interaction between graphene and PAQS through an efficient wrapping
structure. This approach opens a universal way to develop cathode materials for
powerful batteries with different metal-based counter electrodes.
PMID- 28425697
TI - Conserved Helix-Flanking Prolines Modulate Intrinsically Disordered
Protein:Target Affinity by Altering the Lifetime of the Bound Complex.
AB - Appropriate integration of cellular signals requires a delicate balance of ligand
target binding affinities. Increasing the level of residual structure in
intrinsically disordered proteins (IDPs), which are overrepresented in these
cellular processes, has been shown previously to enhance binding affinities and
alter cellular function. Conserved proline residues are commonly found flanking
regions of IDPs that become helical upon interacting with a partner protein.
Here, we mutate these helix-flanking prolines in p53 and MLL and find opposite
effects on binding affinity upon an increase in free IDP helicity. In both cases,
changes in affinity were due to alterations in dissociation, not association,
rate constants, which is inconsistent with conformational selection mechanisms.
We conclude that, contrary to previous suggestions, helix-flanking prolines do
not regulate affinity by modulating the rate of complex formation. Instead, they
influence binding affinities by controlling the lifetime of the bound complex.
PMID- 28425699
TI - Synthesis of NPN-Coordinated Tantalum Alkyl Complexes and Their Hydrogenolysis:
Isolation of a Terminal Tantalum Hydride Incorporating a Doubly Cyclometalated
NPN Scaffold.
AB - The closely related benzylene-linked diaminophosphines PhP(CH2C6H4-o-NHPh)2 (AH2)
and PhP(C6H4-o-CH2NHXyl)2 (BH2 with Xyl = 3,5-Me2C6H3) were employed for the
synthesis of tantalum(V) alkyls, which were then studied with respect to
hydrogenolysis. In the case of AH2, the tantalum trimethyl complex [Ta(A)Me3] (1)
and the tantalum hydrocarbyl complex [Ta(A)(CH2SiMe3)(eta2-EtC=CEt)] (2) were
prepared from the ligand's dilithium salt (A)Li2(diox). Upon hydrogenolysis of 1
and 2, the formation of methane and SiMe4, respectively, was observed, but well
defined tantalum hydrides could not be detected. In the case of BH2, the
cyclometalated species [Ta(B*)(NMe2)2] (3 with B* = kappa4-N,P,N,C-(PhP(C6H4-o
CH2NXyl)(C6H4-o-CHNXyl))3-) was isolated and converted to the corresponding
diiodo species [Ta(B*)I2] (4). Treatment of 4 with LiCH2SiMe3 resulted in the
isolation of the corresponding dialkyl complex [Ta(B*)(CH2SiMe3)2] (5), which was
converted to the doubly cyclometalated monoalkyl complexes
[Ta(B**)(CH2SiMe3)(PMe3)] (6 with B** = kappa5-C,N,P,N,C-(PhP(C6H4-o-CHNXyl)2)4-)
and [Ta(B**)(CH2SiMe3)(dmpe)] (7) via reaction with PMe3 and dmpe, respectively.
In contrast to 5 and 6, 7 was found to react cleanly with dihydrogen to afford
the corresponding terminal tantalum(V) hydride [Ta(B**)(H)(dmpe)] (8). Upon
reaction of 7 with D2, the deuteride [Ta(d2-B**)(D)(dmpe)] (9) was obtained and
found to contain deuterium atoms in the methine positions of both
tantalaaziridine subunits. The partially deuterated derivatives
[Ta(B**)(D)(dmpe)] (10) and [Ta(d2-B**)(H)(dmpe)] (11) were generated via
reaction of 8 and 9 with PhSiD3 and PhSiH3, respectively. Prior to the addition
of gaseous D2 or H2, no H/D scrambling was observed in 10 or 11, indicating that
the exchange of the methine positions proceeds via addition of D2 or H2 across
the tantalaaziridine Ta-C bonds.
PMID- 28425700
TI - Reaction of the Tricyanoborate Dianion [B(CN)3]2- with HgCl2.
AB - The very reactive [B(CN)3]2- dianion has a strongly nucleophilic boron atom and
can be used for the synthesis of tricyanoborates, which otherwise are difficult
to access. Herein the reaction of this anion with HgCl2 is reported. The main
product is the anionic mercury complex [Hg(B(CN)3)2]2-. Heteronuclear NMR
spectroscopic experiments shows that the reaction proceeds via the intermediate
[ClHgB(CN)3]2-. Even though [Hg(B(CN)3)2]2- is the main product, it is difficult
to obtain it in pure form, because it slowly decomposes in the presence of water
and air to [(NC)HgB(CN)3]-. All three anions were fully characterized by
hetereonuclear NMR spectroscopy (11B, 13C, and 199Hg). Single-crystal X-ray
diffraction studies of the salts K[ClHgB(CN)3], [Ph4P]2[Hg(B(CN)3)2],
K[(NC)HgB(CN)3], and [Ph4P][(NC)HgB(CN)3] revealed linear coordination
environments around mercury for all anions. The Hg-B bonds range from 2.219(5) A
in [Hg(B(CN)3)2]2- to 2.148(11) A in [ClHgB(CN)3]-, are in accord with the sum of
the covalent radii of mercury and boron, and can be described as covalent single
bonds. A comparison with related complexes indicates that the [B(CN)3]2- dianion
is a stronger ligand than chloride, cyanide, or carbenes. [Hg(B(CN)3)2]2-
hydrolyses in solution only in the presence of oxygen. It is suggested that cis
[Hg(OH)2(B(CN)3)2]2- is formed as a very unstable intermediate, which decomposes
very fast to [(NC)HgB(CN)3]- and other products. The anion cis
[Hg(OH)2(B(CN)3)2]2- would contain mercury in the unusual oxidation state +IV.
Quantum-chemical calculations were performed to support this assumption.
PMID- 28425702
TI - Oxidatively Induced C-H Activation at High Valent Nickel.
AB - This communication describes a series of oxidatively induced intramolecular arene
C-H activation reactions of NiII model complexes to yield NiIV sigma-aryl
products. These reactions proceed within 10 min at room temperature, which
represents among the mildest conditions reported for C-H cleavage at a Ni center.
A combination of density functional theory and preliminary experimental
mechanistic studies implicate a pathway involving initial 2e- oxidation of the
NiII starting materials by the F+ transfer reagent N-fluoro-2,4,6
trimethylpyridinium triflate followed by triflate-assisted C-H cleavage at NiIV
to yield the products.
PMID- 28425701
TI - Effects of Glutamate Receptor Activation on Local Oxygen Changes.
AB - Glutamate is ubiquitous throughout the brain and serves as the primary excitatory
neurotransmitter. Neurons require energy to fire, and energetic substrates (i.e.,
O2, glucose) are renewed via cerebral blood flow (CBF) to maintain metabolic
homeostasis. Magnetic resonance brain functionality studies rely on the
assumption that CBF and neuronal activity are coupled consistently throughout the
brain; however, the origin of neuronal activity does not always coincide with
signals indicative of energy consumption (e.g., O2 decreases) at high spatial
resolutions. Therefore, relationships between excitatory neurotransmission and
energy use must be evaluated at higher resolutions. In this study, we showed that
both endogenously released and exogenously ejected glutamate decrease local
tissue O2 concentrations, but whether hyperemic O2 restoration followed depended
on the stimulus method. Electrically stimulating the glutamatergic
corticostriatal pathway evoked biphasic O2 responses at striatal terminals: first
O2 decreased, then concentrations increased above baseline. Using iontophoresis
to locally eject ionotropic glutamate receptor antagonists revealed that these
receptors only influenced the O2 decrease. We compared electrical stimulation to
iontophoretic glutamate stimulation, and measured concurrent single-unit activity
and O2 to limit both stimulation and recordings to <50 MUm radius from our
sensor. Similarly, iontophoretic glutamate delivery elicited monophasic O2
decreases without subsequent increases.
PMID- 28425703
TI - Influence of the Oxygen Electrode Open Ratio and Electrolyte Evaporation on the
Performance of Li-O2 Batteries.
AB - This study experimentally investigates and numerically simulates the influence of
the cathode electrode open ratio (ratio of oxygen-opening area to the total
electrode surface area) on the performance of Li-O2 batteries at various
discharge current densities. At the current density of 0.1 mA/cm2, the maximum
discharge capacity is achieved at 25% open ratio among the tested open ratios (0
100%). As the open ratio increases from 25% to 100%, the specific discharge
capacity decreases from 995 to 397 mA h/gcarbon. A similar trend is observed at
0.3 mA/cm2, while the maximum discharge capacity is obtained at 3% open ratio
among the tested open ratios. The model that assumes the electrode is always
fully saturated by the electrolyte does not obtain similar trends with
experimental results, while the model that considers electrolyte loss by
evaporation and the volume change of the solid obtains the same trend with
experimental observations. The open ratio governs not only availability of oxygen
but also the evaporation of the electrolyte and the contact resistance. The
faster evaporation of the electrolyte at a higher open ratio can be the main
reason for the decrease of the discharge capacity, especially when the open ratio
is relatively high (above 25%). Meanwhile, the contact resistance of the battery,
measured by the electrochemical impedance spectroscopy (EIS), increases from 3.97
to 7.02 Omega when the open ratio increased from 3% to 95%. The increase of the
Ohmic overpotential, however, is negligible (on the order of millivolts) because
of the low discharge and charge current rates (on the order of 0.1 mA).
PMID- 28425704
TI - An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while
Remodeling Mature Amyloid Fibrils.
AB - Protein aggregation is a hallmark of several neurodegenerative diseases,
including Alzheimer's and Parkinson's diseases. It has been shown that lysine
residues play a key role in the formation of these aggregates. Thus, the ability
to disrupt aggregate formation by covalently modifying lysine residues could lead
to the discovery of therapeutically relevant antiamyloidogenesis compounds.
Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit
amyloid aggregation. Using alpha-synuclein and Abeta1-40 as model amyloidogenic
proteins, we observed that IQ was able to react with lysine residues and reduce
amyloid aggregation. We also observed that IQ reacted with free amines within the
amyloid fibrils preventing their dissociation and seeding capacity.
PMID- 28425705
TI - Facile Aqueous-Phase Synthesis of the PtAu/Bi2O3 Hybrid Catalyst for Efficient
Electro-Oxidation of Ethanol.
AB - In this work, we present a facile aqueous-phase synthesis of a hybrid catalyst
consisting of PtAu alloy supported on Bi2O3 microspheres. Multistep reduction of
HAuCl4 and K2PtCl4 salts on Bi2O3 and subsequent annealing lead to the formation
of this hybrid catalyst. To the best of our knowledge, this is the first report
of using Bi2O3 as a catalyst support in fuel cell applications. The material was
characterized by powder X-ray diffraction and various microscopic techniques.
This composite showed remarkable activity as well as stability toward the electro
oxidation of ethanol in comparison to commercially available Pt/C. The order of
the reactivity was found to be commercial Pt/C (50.4 mA/m2mgPt-1) < Pt/Bi2O3(10)
(108 mA/m2mgPt-1) < PtAu/Bi2O3(10) (459 mA/m2mgPt-1). The enhancement in the
activity can be explained through cooperative effects, namely, ligand effects of
gold and Bi2O3 support, which helps in removing carbon monoxide molecules to
avoid the poisoning of the Pt active sites.
PMID- 28425706
TI - Allosteric Autoinhibition Pathway in Transcription Factor ERG: Dynamics Network
and Mutant Experimental Evaluations.
AB - Allosteric autoinhibition exists in many transcription factors. The ERG proteins
exhibit autoinhibition on DNA binding by the C-terminal and N-terminal inhibitory
domains (CID and NID). However, the autoinhibition mechanism and allosteric
pathway of ERG are unknown. In this study we intend to elucidate the residue
level allosteric mechanism and pathway via a combined approach of computational
and experimental analyses. Specifically computational residue-level fluctuation
correlation data was analyzed to reveal detailed dynamics signatures in the
allosteric autoinhibition process. A hypothesis of "NID/CID binding induced
allostery" is proposed to link similar structures and different protein
functions, which is subsequently validated by perturbation and mutation analyses
in both computation and experiment. Two possible allosteric autoinhibition
pathways of L286-L382-A379-G377-I360-Y355-R353 and L286-L382-A379-G377-I360-Y355-
A351-K347-R350 were identified computationally and were confirmed by the
computational and experimental mutations. Specifically we identified two mutation
sites on the allosteric inhibition pathways, L286P/Q383P (NID/CID binding site)
and I360G (pathway junction), which completely restore the wild type DNA binding
affinity. These results suggest that the putative protein structure-function
relationship may be augmented with a general relationship of protein
"structure/fluctuation-correlation/function" for more thorough analyses of
protein functions.
PMID- 28425707
TI - Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin
Structural Fold.
AB - Granulins are a family of protein growth factors that are involved in cell
proliferation. An orthologue of granulin from the human parasitic liver fluke
Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates
wound repair. Recombinant Ov-GRN-1 production is complex and poses an obstacle
for clinical development. To identify the bioactive region(s) of Ov-GRN-1, four
truncated N-terminal analogues were synthesized and characterized structurally
using NMR spectroscopy. Peptides that contained only two native disulfide bonds
lack the characteristic granulin beta-hairpin structure. Remarkably, the
introduction of a non-native disulfide bond was critical for formation of beta
hairpin structure. Despite this structural difference, both two and three
disulfide-bonded peptides drove proliferation of a human cholangiocyte cell line
and demonstrated potent wound healing in mice. Peptides derived from Ov-GRN-1 are
leads for novel wound healing therapeutics, as they are likely less immunogenic
than the full-length protein and more convenient to produce.
PMID- 28425708
TI - Revealing Multiple Pathways in T4 Lysozyme Substep Conformational Motions by
Single-Molecule Enzymology and Modeling.
AB - Enzyme conformational dynamics play crucial roles in catalytic functions.
Obtaining molecular level insights into the conformational transition dynamics of
enzyme-substrate complex from the inactive state to the active state is
fundamental for understanding enzymatic function and dynamics. Here, we report
our progress on the real-time conformational transition dynamics of T4 lysozyme
under enzymatic reactions using single-molecule fluorescence resonance energy
transfer. The time duration in forming the active enzyme-substrate complex state
(ES*) shows distinctive Poisson and non-Poisson statistics, including exponential
and nonexponential, convoluted Poisson distributions, and Gaussian-like
distributions. These complex dynamic behaviors of T4 lysozyme are in excellent
agreement with a Markov dynamic simulation and a transition steps modeling.
Specifically, we are able to obtain mechanistic understandings: (1) Transiting
from enzyme (E) to ES*, T4 lysozyme hinge-bending conformational changes undergo
multiple steps following multiple pathways. In the case of shortest pathway, this
transition only requires one elementary transition or reaction step. (2) Substep
conformational motions, associating with multiple nuclear coordinates and a
common projected FRET-sensitive nuclear coordinate, can give rise to multiple
conformational intermediate states. (3) The consequence of the multiple pathways,
intermediate states, and nuclear coordinates is the time bunching effect; i.e.,
time durations of conformational changes tend to bunch in a narrowly distributed
time window. The physical picture of multiple intermediate states along with
bunching effect suggests that the conformational dynamics of T4 lysozyme shows a
complementary characteristic behavior of convoluted enzyme conformation selection
and induced-fit dynamics driven by substrate-enzyme interactions.
PMID- 28425710
TI - Solvation Structure of 1,3-Butanediol in Aqueous Binary Solvents with
Acetonitrile, 1,4-Dioxane, and Dimethyl Sulfoxide Studied by IR, NMR, and
Molecular Dynamics Simulation.
AB - The solvation structure of 1,3-butanediol (1,3-BD) in aqueous binary solvents of
acetonitrile (AN), 1,4-dioxane (DIO), and dimethyl sulfoxide (DMSO) at various
mole fractions of organic solvent xOS has been clarified by means of infrared
(IR) and 1H and 13C NMR. The change in the wavenumber of O-H stretching vibration
of 1,3-BD in the three systems suggested that water molecules which are initially
hydrogen-bonded with the 1,3-BD hydroxyl groups in the water solvent (xOS = 0)
are more significantly replaced by organic solvent molecules in the order of DMSO
? DIO > AN. This agrees with the order of the electron donicities of the organic
solvents. The 1H and 13C chemical shifts of 1,3-BD also revealed the most
remarkable replacement of water molecules on the hydroxyl groups by DMSO. In
contrast to the DMSO system, the O-H vibration band of 1,3-BD in the AN and DIO
systems suggested the formation of the intramolecular hydrogen bond between the
two hydroxyl groups of 1,3-BD above xOS = ~0.9. To further evaluate the
intramolecular hydrogen bonding of 1,3-BD in AN-water binary solvents, molecular
dynamics (MD) simulations and NMR experiments for spin-lattice relaxation times
T1 and 1H-1H nuclear Overhauser effect (NOE) were conducted on 1,3-BD in the AN
system. These results showed the intramolecular hydrogen bond within 1,3-BD in
the AN-water binary solvents in the high AN mole fraction range of xAN > 0.9.
Especially, the pair correlation functions g(r) of the OH-O interactions of 1,3
BD obtained from the MD simulations indicated that the intramolecular hydrogen
bond remarkably increases in the AN solvent as the xAN rises to the unity.
PMID- 28425711
TI - Influence of Surfactants on Sodium Chloride Crystallization in Confinement.
AB - We study the influence of different surfactants on NaCl crystallization during
evaporation of aqueous salt solutions. We found that at concentrations of sodium
chloride close to saturation, only the cationic surfactant CTAB and the nonionic
surfactant Tween 80 remain stable. For the nonionic surfactant, the high
concentration of salt does not significantly change either the critical micellar
concentration (CMC) or the surface tension at the CMC; for the cationic
surfactant, the CMC is reduced by roughly 2 orders of magnitude upon adding the
salt. The presence of both types of surfactants in the salt solution delays the
crystallization of sodium chloride with evaporation. This, in turn, leads to high
supersaturation which induces the rapid precipitation of a hopper crystal in the
bulk. The crystallization inhibitor role of these surfactants is shown to be
mainly due to the passivation of nucleation sites at both liquid/air and
solid/liquid interfaces rather than a change in the evaporation rate which is
found not to be affected by the presence of the surfactants. The adsorption of
surfactants at the liquid/air interface prevents the crystallization at this
location which is generally the place where the precipitation of sodium chloride
is observed. Moreover, sum frequency generation spectroscopy measurements show
that the surfactants are also present at the solid/liquid interface. The
incorporation of the surfactants into the salt crystals is investigated using a
novel, but simple, method based on surface tension measurements. Our results show
that the nonionic surfactant Tween 80 is incorporated in the NaCl crystals but
the cationic surfactant CTAB is not. Taken together, these results therefore
allow us to establish the effect of the presence of surfactants on sodium
chloride crystallization.
PMID- 28425709
TI - Beyond Structural Biology to Functional Biology: Solid-State NMR Experiments and
Strategies for Understanding the M2 Proton Channel Conductance.
AB - In terms of structural biology, solid-state NMR experiments and strategies have
been well established for resonance assignments, leading to the determination of
three-dimensional structures of insoluble membrane proteins in their native-like
environment. It is also known that NMR has the unique capabilities to
characterize structure-function relationships of membrane-bound biological
systems beyond structural biology. Here, we report on solid-state NMR experiments
and strategies for extracting functional activities on a sub-millisecond time
scale. Specifically, we use the His37-labeled full length M2 (M2FL) protein of
the Influenza A virus embedded in synthetic lipid bilayers as an example to
characterize the proton conduction mechanism and kinetics. The integral membrane
M2 protein assembles as a tetrameric bundle to form a proton-conducting channel
that is activated by low pH and is essential for the viral lifecycle. Our results
present convincing evidence for the formation of imidazolium-imidazole hydrogen
bonds in the His37 tetrad at low pH and that these hydrogen bonds have a low
barrier that facilitates the proton conduction mechanism in the M2FL protein.
Moreover, it has been possible to measure hydronium ion exchange between water
and the protons in the His37 NH bonds based on chemical exchange spectroscopy
with minimized spin diffusion. The results identify an exchange rate constant of
~4000 s-1 for pH 5.8 at -10 degrees C.
PMID- 28425712
TI - Synthesis and Photooxidation of the Trisubstituted Oxazole Fragment of the Marine
Natural Product Salarin C.
AB - The eastern section of the macrocyclic marine natural product salarin C from the
sponge Fascaplysinopsis sp. was synthesized employing a halogen dance reaction to
assemble the trisubstituted oxazole moiety. The synthesis was inspired by
Kashman's hypothesis on the biomimetic oxidation of salarin C to salarin A. Clean
conversion to the triacylamine partial structure of salarin A occurred on
treatment with photochemically generated singlet oxygen. Thus, a Wasserman-type
oxidative rearrangement is chemically possible in this case.
PMID- 28425713
TI - Synthesis of Diverse N-Acryloyl Azetidines and Evaluation of Their Enhanced Thiol
Reactivities.
AB - Acyl azetidines exhibit nonplanar hybridization, leading to lower amide-like
character of the corresponding (O)C-N bonds. This impacts N-acryloyl azetidines
by producing enhanced electrophilicy at appended Michael acceptors. Herein,
reactivity data are reported in the presence of glutathione (GSH) in phosphate
buffer (pH 7.4) at 37 degrees C. Wide reactivity ranges are observed by varying
substitution at the Michael acceptor or by modulating the electron-withdrawing
character of substituents at the C3 position of the azetidine.
PMID- 28425714
TI - Prehydrated One-Electron Attachment to Azido-Modified Pentofuranoses: Aminyl
Radical Formation, Rapid H-Atom Transfer, and Subsequent Ring Opening.
AB - Methyl 2-azido-2-deoxy-alpha-d-lyxofuranoside (1a) and methyl 2-azido-2-deoxy
beta-d-ribofuranoside (2) were prepared from d-xylose or d-arabinose,
respectively. Employing ESR and DFT/B3LYP/6-31G* calculations, we investigated
(i) aminyl radical (RNH.) formation and (ii) reaction pathways of RNH..
Prehydrated electron attachment to 1a and 2 at 77 K produced transient azide
anion radical (RN3.-) which reacts via rapid N2 loss at 77 K, forming nitrene
anion radical (RN.-). Rapid protonation of RN.- at 77 K formed RNH. and -OH. 15N
labeled-1a confirmed this mechanism. Investigations employing in-house
synthesized site-specifically deuterated derivatives of 1a (e.g., CH3 (1b), C4
(1c), and C5 (1d)) established that (a) a facile intramolecular H atom transfer
from C5 to RNH. generated C5. and RNH2. C5. formation had a small deuterium
kinetic isotope effect suggesting that this reaction does not occur via direct H
atom abstraction. (b) Subsequently, C5. underwent a facile unimolecular
conversion to ring-opened C4.. Identification of ring-opened C4. intermediate
confirms the mechanism of C5'. mediated unaltered base release associated with
DNA-strand break. However, for 2, ESR studies established thermally activated
intermolecular H atom abstraction by RNH. from the methyl group at C1. Thus,
sugar ring configuration strongly influences the site and pathway of RNH.
mediated reactions in pentofuranoses.
PMID- 28425715
TI - Five-Fold Ordering in High-Pressure Perovskites RMn3O6 (R = Gd-Tm and Y).
AB - Cation and anion ordering plays an important role in the properties of materials,
in particular, in the properties of perovskite materials. Here we report on
unusual 5-fold cation/charge ordering in high-pressure-synthesized (at 6 GPa and
~1670 K) RMn3O6 perovskites with R = Gd-Tm and Y. R3+, Mn2+, and Mn3+ cations are
ordered at the A site in two separate chains consisting of R3+ and alternating
Mn2+ (in tetrahedral coordination) and Mn3+ (in square-planar coordination),
while Mn3+ and mixed-valent Mn3+/Mn4+ are ordered at the B site in layers. The
ordering can be represented as [R3+Mn2+0.5Mn3+0.5]A[Mn3+Mn3.5+]BO6. The triple
cation ordering observed at the A site is very rare, and the layered double-B
site ordering is also scarce. RMn3O6 compounds crystallize in space group Pmmn
with a = 7.2479(2) A, b = 7.4525(3) A, and c = 7.8022(2) A for DyMn3O6 at 213 K,
and they are structurally related to CaFeTi2O6. They are prone to
nonstoichiometry, R1-deltaMn3O6-1.5delta, where delta = -0.071 to -0.059 for R =
Gd, delta = 0 for R = Dy, delta = 0.05-0.1 for R = Ho and Y, and delta = 0.12 for
R = Er and Tm. They show complex magnetic behaviors with several transition
temperatures, and their magnetic properties are highly sensitive to the delta
values.
PMID- 28425716
TI - Reactions of N2O5 with Salty and Surfactant-Coated Glycerol: Interfacial
Conversion of Br- to Br2 Mediated by Alkylammonium Cations.
AB - Gas-liquid scattering and product-yield experiments are used to investigate
reactions of N2O5 with glycerol containing Br- and surfactant ions. N2O5 oxidizes
Br- to Br2 for every solution tested: 2.7 M NaBr, 0.03 M tetrahexylammonium
bromide (THABr), 0.03 M THABr + 0.5 M NaBr, 0.03 M THABr + 0.5 M NaCl, 0.03 M
THABr + 0.01 M sodium dodecyl sulfate (SDS), and 0.01 M cetyltrimethylammonium
bromide (CTABr). N2O5 also reacts with glycerol itself to produce mono- and
dinitroglycerin. Surface tension measurements indicate that 0.03 M THABr and 2.7
M NaBr have similar interfacial Br- concentrations, though their bulk Br-
concentrations differ by 90-fold. We find that twice as much Br2 is produced in
the presence of THA+, implying that the conversion of Br- to Br2 is initiated at
the interface, perhaps mediated by the charged, hydrophobic pocket within the
surface THA+ cation. The addition of 0.5 M NaBr, 0.5 M NaCl, or 0.01 M SDS to
0.03 M THABr lowers the Br2 production rate by 23%, 63%, and 67% of the THABr
value, respectively. When CTA+ is substituted for THA+, Br2 production drops to
12% of the THABr value. The generation of Br2 under such different conditions
implies that trace amounts of surface-active alkylammonium ions can catalyze
interfacial N2O5 reactions, even when salts and other surfactants are present.
PMID- 28425717
TI - An Experimental and Molecular Dynamics Study of Red Fluorescent Protein mCherry
in Novel Aqueous Amino Acid Ionic Liquids.
AB - The search for biocompatible ionic liquids (ILs) with novel biochemical and
biomedical applications has recently gained greater attention. In this report, we
characterize the effects of two novel amino acid-based aqueous ILs composed of
tetramethylguanidinium (TMG) and amino acids on the structure and stability of a
widely used red fluorescent protein (mCherry). Our experimental data shows that
while the aspartic acid-based IL (TMGAsp) has effects similar to previously
studied conventional ILs (BMIBF4, EMIAc, and TMGAc), the alanine-based IL
(TMGAla) has a much stronger destabilization effect on the protein structure.
Addition of 0.30 M TMGAla to mCherry decreases the unfolding temperature from 83
to 60 degrees C. Even at 25 degrees C, TMGAla results in a blue shift of the
mCherry absorbance and fluorescence peaks and an increased Stokes shift.
Molecular dynamics simulations show that the chromophore conformation and its
interaction with mCherry with TMGAla are changed relative to those with TMGAsp or
in the absence of ILs. Protein-ILs contact analysis indicates that the mCherry
Asp interactions are hydrophilic but the (fewer) mCherry-Ala interactions are
more hydrophobic and may modulate the TMG interaction with the protein. Hence,
the anion hydrophobicity may explain the special TMGAla destabilization of
mCherry.
PMID- 28425718
TI - Testing High Concentrations of Membrane Active Antibiotic Chlorhexidine Via
Computational Titration and Calorimetry.
AB - Coarse-grained strategies for membrane simulations are designed to increase
efficiency for larger and more complex molecular dynamics simulations. For
membrane active antibiotics, the concentration dependence of their action
presents a tremendous challenge in simulation scale. In this study, we examine
the effects of concentration for the popular membrane active antibacterial drug
chlorhexidine. It presents an interesting biophysical modeling test, where from
experimental experience we know that model membranes of 1,2-dimyristoyl-sn
glycero-3-phosphocholine (DMPC) can absorb very high quantities of the drug
without disruption. We construct a coarse-grained model of chlorhexidine in three
different charged states and compare to previous all-atom simulations and new
experiments. Using large, long-time, and unbiased simulations of chlorhexidine
inserting into the lipid bilayer, we find little changes to the functional
structure of a DMPC membrane up through concentrations of 15:100 drug:lipid,
where the slowing rate of continued insertion tests the capabilities of even this
coarse-grained approach. We validate our simulations with computational
calorimetry measurements, and show that they agree with new experimental data
from differential scanning calorimetry.
PMID- 28425719
TI - Adsorption of Nitrate and Bicarbonate on Fe-(Hydr)oxide.
AB - In this work, we used density functional theory calculations to study the
resulting complexes of adsorption and of inner- and outer-sphere adsorption-like
of bicarbonate and nitrate over Fe-(hydr)oxide surfaces using acidic, neutral,
and basic simulated pH conditions. High-spin states that follow the 5N + 1 (N is
the number of Fe atoms, each having five unpaired electrons) rule are preferred.
Monodentate mononuclear (MM1) surface complexes are shown to lead to the most
favorable thermodynamic adsorption for both bicarbonate and nitrate with -63.91
and -28.25 kJ/mol, respectively, under neutral conditions. Our results suggest
that four types of regular and charged-assisted hydrogen bonds are involved in
the adsorption process; all of them can be classified as closed-shell (long-range
or ionic). The formal charges induce unusually short and strong hydrogen bonds.
The ability of high multiplicity states of Fe clusters to adsorb oxyanions in
solvated environments arises from orbital interactions: the 4s virtual orbitals
in Fe have a large affinity for the 2p-type electron pairs of oxygens.
PMID- 28425720
TI - A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos.
AB - The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing
the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to
cause their ubiquitination and degradation. Here we describe CC-220 (compound 6),
a cereblon modulator in clinical development for systemic lupus erythematosis and
relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher
affinity than lenalidomide or pomalidomide. Consistent with this, the cellular
degradation of Ikaros and Aiolos is more potent and the extent of substrate
depletion is greater. The crystal structure of cereblon in complex with DDB1 and
compound 6 reveals that the increase in potency correlates with increased
contacts between compound 6 and cereblon away from the modeled binding site for
Ikaros/Aiolos. These results describe a new cereblon modulator which achieves
greater substrate degradation via tighter binding to the cereblon E3 ligase and
provides an example of the effect of E3 ligase binding affinity with relevance to
other drug discovery efforts in targeted protein degradation.
PMID- 28425721
TI - Co(III)-Catalyzed Enaminone-Directed C-H Amidation for Quinolone Synthesis.
AB - We report herein the development of a Co(III)-catalyzed enaminone-directed C-H
amidation method for synthetic access to quinolones, an important heterocyclic
scaffold for diverse pharmaceutically active structures. The C-H coupling with
dioxazolones and subsequent deacylation of an installed amide group allow
consecutive C-N coupling generation of quinolones with wide-ranging compatible
substituent patterns.
PMID- 28425722
TI - Giant Electrostrictive Response and Piezoresistivity of Emulsion Templated
Nanocomposites.
AB - Using an emulsion road and optimizing the dispersion process, we prepare polymer
carbone nanotubes (CNT) and polymer reduced graphene oxide (rGO) composites. The
introduction of conductive nanoparticles into polymer matrices modifies the
electronic properties of the material. We show that these materials exhibit giant
electrostriction coefficients in the intermediate filler concentration (below 1
wt %). This makes them very promising for applications such as capacitive sensors
and actuators. In addition, the values of the piezoresistivity measured in the
high filler concentration situation are at least an order of magnitude greater
than the one reported in the literature. This opens the way to use these
materials for stress or strain sensor applications considering their giant
responses to mechanical deformations.
PMID- 28425723
TI - Decreases in implicit self-esteem explain the racial impact of microaggressions
among Asian Americans.
AB - Asian Americans are commonly perceived as perpetual foreigners and, therefore,
not "true" Americans. Asian Americans report inquiries about nationality and
English abilities as the most common forms of racial microaggressions perpetrated
by White Americans (Sue, 2015). Race theorists assert that these microaggressions
are race-related and marginalize Asian Americans. Scholars have claimed that
these subtle acts are harmful, yet only a few studies have uncovered the
mechanisms by which racial microaggressions affect mental and physical well-being
(Ong, Burrow, Fuller-Rowell, Ja, & Sue, 2013; Wong, Derthick, David, Saw, &
Okazaki, 2013). The current study conceptualized racial microaggressions as a
stressor to address the major gaps in research. Specifically, this study (a)
experimentally tested the race-related nature of the microaggression event to
determine whether a White American perpetrator would elicit more stress in Asian
Americans compared to an Asian American perpetrator and (b) examined threats to
explicit and implicit self-esteem as possible mediators of microaggression
generated stress. Findings confirmed that the race of the perpetrator did have an
impact on stress among Asian Americans. In the multiple meditation analysis,
experience with a White American perpetrator, compared to an Asian American
perpetrator, lowered implicit self-esteem, which resulted in more stress.
Implications and strategies for counseling Asian American clients are discussed.
(PsycINFO Database Record
PMID- 28425724
TI - Factors impacting sense of community among adults with brain injury.
AB - PURPOSE: Despite increasing interest in examining community outcomes following
disability, sense of community (SOC) has received relatively no attention in the
rehabilitation literature. SOC refers to feelings of belonging and attachment one
has for a community and is of particular relevance for people with brain injury
who are at increased risk of social isolation. The aim of this study was to
investigate factors contributing to SOC for individuals with brain injury.
METHOD: Members from 2 brain injury associations (n = 98) participated in this
survey-based study. Hierarchical regression analysis was used to explore
demographic, disability-related, community and social participation variables'
impact on SOC with regard to one's town or city. Follow-up mediation analyses
were conducted to explore relationships among social self-efficacy, support
network, neighboring behavior, and SOC. RESULTS: Findings indicated that
disability-related and community variables accounted for over 40% of the variance
in SOC. Size of social support network was the only significant independent
contributor to SOC variance. Follow-up analyses provided support for (a) the
partial mediating effect of social support network size on the relationship
between social self-efficacy and SOC, and (b) the mediating effect of neighboring
behavior on the relationship between social self-efficacy and social support
network size. CONCLUSIONS: Findings from this study highlight the particular
importance of self-efficacy, social support, and neighboring behaviors in
promoting SOC for people with brain injury. Recommendations are provided to
advance research efforts and inform intervention approaches to improve the felt
experience of community among people with brain injury. (PsycINFO Database Record
PMID- 28425725
TI - "Defining 'peerness' in peer-delivered health and wellness interventions for
serious mental illness": Correction to Muralidharan et al. (2017).
AB - Reports an error in "Defining "peerness" in peer-delivered health and wellness
interventions for serious mental illness": Response to letter to the editor" by
Jody Silver and Patricia B. Nemec (Psychiatric Rehabilitation Journal, 2017[Mar],
Vol 40[1], 116). The article was mislabeled as Editorial and should be a Comment.
The Response to Letter to the Editor section should be a Reply and now has its
own http://dx.doi.org/10.1037/ h0101580. (The following abstract of the original
article appeared in record 2017-13876-001.) Replies to comments by Muralidharan
et al (see record 2017-13255-009) on the original article by Silver and Nemec
(see record 2016-43088-001). The original authors thank the commentators for
raising additional questions regarding "peerness." They were honored that their
paper prompted this thought and effort to submit comments. (PsycINFO Database
Record
PMID- 28425726
TI - Comparisons between the Minnesota Multiphasic Personality Inventory-Adolescent
Restructured Form (MMPI-A RF) and MMPI-A in adolescent psychiatric inpatients.
AB - This study explored the association between the Minnesota Multiphasic Personality
Inventory (MMPI)-Adolescent-Restructured Form (MMPI-A-RF) and the MMPI-Adolescent
(MMPI-A) form in a sample of 3,516 adolescents receiving inpatient psychiatric
treatment, including 2,798 adolescents meeting validity inclusion cutoffs for
both measures. There was 92.5% agreement rate with respect to global
identification of cases as valid or invalid and some empirical support for
lowering interpretive cutoffs for validity scales on the MMPI-A-RF. The MMPI-A-RF
Demoralization Scale (RCd) was shown to correlate significantly less strongly
with Restructured Clinical (RC) scales than with MMPI-A clinical scales. RC
scales also demonstrated significantly lower mean interscale correlations than
MMPI-A clinical scales. As expected, this greater level of scale independence
resulted in significantly fewer profiles with multiple scale elevations. As was
anticipated, with the exception of RC1 predicting MMPI-A hypochondriasis,
correlational and classification agreement analyses suggested moderate
associations between the RC and MMPI-A clinical scales, but somewhat stronger
agreement between comparable PSY-5 scales. Changes in interpretive cutoff
procedures for the RC scales, including RCd, also resulted in 5.5% fewer "within
normal limits" profiles than the use of MMPI-A with all 10 clinical scales.
Finally, stepwise linear regression analyses indicated that MMPI-A-RF Higher
Order scales were best predicted by those MMPI-A clinical scale combinations that
they are purported to be linked with in the MMPI-A-RF manual. (PsycINFO Database
Record
PMID- 28425727
TI - Longitudinal associations of neighborhood collective efficacy and maternal
corporal punishment with behavior problems in early childhood.
AB - Neighborhood and parenting influences on early behavioral outcomes are strongly
dependent upon a child's stage of development. However, little research has
jointly considered the longitudinal associations of neighborhood and parenting
processes with behavior problems in early childhood. To address this limitation,
this study explores the associations of neighborhood collective efficacy and
maternal corporal punishment with the longitudinal patterns of early
externalizing and internalizing behavior problems. The study sample consisted of
3,705 families from a nationally representative cohort study of urban families.
Longitudinal multilevel models examined the associations of collective efficacy
and corporal punishment with behavior problems at age 3, as well as with patterns
of behavior problems between the ages 3 to 5. Interactions between the main
predictors and child age tested whether neighborhood and parent relationships
with child behavior varied over time. Mediation analysis examined whether
neighborhood influences on child behavior were mediated by parenting. The models
controlled for a comprehensive set of possible confounders at the child, parent,
and neighborhood levels. Results indicate that both maternal corporal punishment
and low neighborhood collective efficacy were significantly associated with
increased behavior problems. The significant interaction between collective
efficacy and child age with internalizing problems suggests that neighborhood
influences on internalizing behavior were stronger for younger children. The
indirect effect of low collective efficacy on behavior problems through corporal
punishment was not significant. These findings highlight the importance of
multilevel interventions that promote both neighborhood collective efficacy and
nonphysical discipline in early childhood. (PsycINFO Database Record
PMID- 28425728
TI - Parent- and teacher-child relationships and engagement at school entry:
Mediating, interactive, and transactional associations across contexts.
AB - Early school engagement patterns set the stage for short- and long-term academic
behaviors and progress, and low engagement at school entry can give rise to
dysfunctional school behavior and underachievement in later years. Relationships
with parents and teachers provide a foundation upon which children develop the
skills and behaviors that are critical for engagement in early elementary school.
However, the cross-contextual and transactional processes by which these
relationships are associated with engagement in early elementary school remain
unclear. This investigation therefore considers how children's relationships with
parents prior to school entry are indirectly and interactively associated with
1st grade engagement through teacher-child relationships. It also considers how
early cognitive, self-regulatory, and behavioral skills and competencies elicit
these relational responses. This investigation drew upon multimethod data from
triangulated sources (parents, teachers, and direct observation) available within
a large longitudinal study, the National Institute of Child Health and Human
Development Study of Early Child Care and Youth Development. Results indicate
that neither 54-month or 1st grade parent-child relationships were directly
associated with children's engagement in early elementary school. However, 1st
grade teacher conflict was problematic for children's developing engagement. In
turn, teacher conflict partially mediated linkages between maternal sensitivity
and conflict prior to school entry and engagement in 1st grade. Parental
closeness and sensitivity also buffered children against negative associations
between teacher conflict and engagement. Finally, children's early skills and
competencies at 36 months elicited relational processes that were indirectly
associated with engagement. Conceptual, theoretical, and methodological
challenges are also discussed. (PsycINFO Database Record
PMID- 28425729
TI - Some properties of p-curves, with an application to gradual publication bias.
AB - p-curves provide a useful window for peeking into the file drawer in a way that
might reveal p-hacking (Simonsohn, Nelson, & Simmons, 2014a). The properties of p
curves are commonly investigated by computer simulations. On the basis of these
simulations, it has been proposed that the skewness of this curve can be used as
a diagnostic tool to decide whether the significant p values within a certain
domain of research suggest the presence of p-hacking or actually demonstrate that
there is a true effect. Here we introduce a rigorous mathematical approach that
allows the properties of p-curves to be examined without simulations. This
approach allows the computation of a p-curve for any statistic whose sampling
distribution is known and thereby allows a thorough evaluation of its properties.
For example, it shows under which conditions p-curves would exhibit the shape of
a monotone decreasing function. In addition, we used weighted distribution
functions to analyze how 2 different types of publication bias (i.e., cliff
effects and gradual publication bias) influence the shapes of p-curves. The
results of 2 survey experiments with more than 1,000 participants support the
existence of a cliff effect at p = .05 and also suggest that researchers tend to
be more likely to recommend submission of an article as the level of statistical
significance increases beyond this p level. This gradual bias produces right
skewed p-curves mimicking the existence of real effects even when no such effects
are actually present. (PsycINFO Database Record
PMID- 28425731
TI - Changes in perception-action tuning over long time scales: How children and
adults perceive and act on dynamic affordances when crossing roads.
AB - This investigation examined developmental change in how children perceive and act
on dynamic affordances when crossing roads on foot. Six- to 14-year-olds and
adults crossed roads with continuous cross-traffic in a large-screen, immersive
pedestrian simulator. We observed change both in children's gap choices and in
their ability to precisely synchronize their movement with the opening of a gap.
Younger children were less discriminating than older children and adults,
choosing fewer large gaps and more small gaps. Interestingly, 12-year-olds' gap
choices were significantly more conservative than those of 6-, 8-, 10-, and 14
year-olds, and adults. Timing of entry behind the lead vehicle in the gap (a key
measure of movement coordination) improved steadily with development, reaching
adultlike levels by age 14. Coupled with their poorer timing of entry, 6-, 8-,
and 10-year-olds' gap choices resulted in significantly less time to spare and
more collisions than 14-year-olds and adults. Time to spare did not differ
between 12-year-olds, 14-year-olds, and adults, indicating that 12-year-olds'
more conservative gap choices compensated for their poorer timing of entry. The
findings show that children's ability to perceive and act on dynamic affordances
undergoes a prolonged period of development, and that older children appear to
compensate for their poorer movement timing skills by adjusting their gap
decisions to match their crossing actions. Implications for the development of
perception-action tuning and road-crossing skills are discussed. (PsycINFO
Database Record
PMID- 28425730
TI - The relation of anxiety and cognition in Parkinson's disease.
AB - OBJECTIVE: Parkinson's disease (PD) has long been conceptualized as a motor
disorder, but nonmotor symptoms also manifest in the disease and significantly
reduce quality of life. Anxiety and cognitive dysfunction are prevalent nonmotor
symptoms, even in early disease stages, but the relation between these symptoms
remains poorly understood. We examined self-reported anxiety and neurocognitive
function, indexed by measures of executive function (set-shifting and phonemic
fluency), categorical fluency, and attention/working memory. We hypothesized that
anxiety would correlate with cognitive performance. METHOD: The Beck Anxiety
Inventory and cognitive tests (Trail Making, Verbal Fluency, Digit Span) were
administered to 77 nondemented adults with mild to moderate idiopathic PD (39
men, 38 women; Mage = 62.9 years). RESULTS: Higher anxiety was associated with
more advanced disease stage and severity and with poorer set-shifting when using
a derived metric to account for motoric slowing. Depression correlated with
greater anxiety and disease severity, but not with cognitive performance.
CONCLUSIONS: Our findings support the association of anxiety with a specific
domain of executive function, set-shifting, in nondemented individuals with mild
to moderate PD, raising the possibility that treatment of anxiety may alleviate
aspects of executive dysfunction in this population. (PsycINFO Database Record
PMID- 28425732
TI - Distractor probability changes the shape of the attentional template.
AB - Theories of attention commonly refer to the "attentional template" as the
collection of features in working memory that represent the target of visual
search. Many models of attention assume that the template contains a veridical
representation of target features, but recent studies have shown that the target
representation is "shifted" away from distractor features in order to optimize
their distinctiveness and facilitate visual search. Here, we manipulated the
probability of target-similar distractors during a visual search task in 2
groups, and separately measured the contents of the attentional template. We
hypothesized that having a high probability of target-similar distractors would
increase pressure to shift and/or sharpen the target representation in order to
increase the distinctiveness of targets from distractors. We found that the high
similarity group experienced less distractor interference during visual search,
but only for highly target-similar distractors. Additionally, while both groups
shifted the target representation away from the actual target color, the high
similarity group also had a sharper representation of the target color. We
conclude that the contents of the attentional template in working memory can be
flexibly adjusted with multiple mechanisms to increase target-to-distractor
distinctiveness and optimize attentional selection. (PsycINFO Database Record
PMID- 28425733
TI - Contingent capture is weakened in search for multiple features from different
dimensions.
AB - Can observers maintain more than 1 attentional set and search for 2 features in
parallel? Previous studies that relied on attentional capture by irrelevant
distractors to answer this question focused on features from the same dimension
and specifically, on color. They showed that 2 separate color templates can guide
attention selectively and simultaneously. Here, the authors investigated
attentional guidance by 2 features from different dimensions. In three spatial
cueing experiments, they compared contingent capture during single-set versus
dual-set search. The results showed that attention was guided less efficiently by
2 features than by just 1. This impairment varied considerably across target
feature dimensions (color, size, shape and orientation). Confronted with previous
studies, our findings suggest avenues for future research to determine whether
impaired attentional guidance by multiple templates occurs only in cross
dimensional disjunctive search or also in within-dimension search. The present
findings also showed that although performance improved when the target feature
repeated on successive trials, a relevant-feature cue did not capture attention
to a larger extent when its feature matched that of the previous target. These
findings suggest that selection history cannot account for contingent capture and
affects processes subsequent to target selection. (PsycINFO Database Record
PMID- 28425734
TI - A within-person approach to risk for suicidal ideation and suicidal behavior:
Examining the roles of depression, stress, and abuse exposure.
AB - OBJECTIVE: This study tests a novel, within-person model that reexamines
depression and stress as risk factors for suicidal ideation and behavior among
adolescent girls with and without sexual/physical abuse histories. METHOD: This
longitudinal study includes data from 220 adolescent girls between 12 and 16
years of age (M = 14.69 years, SD = 1.37; 61% White). At baseline, adolescents
reported the presence or absence of prior abuse as part of a clinical interview.
At baseline and every 3 months for 18 months, adolescents completed measures of
suicidal ideation and behavior, depressive symptoms, and stress. RESULTS:
Multilevel models examined within-person mean, deviations from within-person
mean, depression, and stress and their interactions with abuse as predictors of
suicidal ideation and behavior. In addition to within-person mean depression,
higher-than-usual depression (odds ratio [OR] = 1.99) and higher-than-usual
stress (OR = 1.53) predicted greater risk of suicidal ideation at each follow-up
assessment. Periods of higher-than-usual stress (1 SD increase) and periods of
higher-than-usual depression (1 SD increase) were associated with an 82% and 57%
increase in the odds of suicidal behavior, respectively, but only among those
with abuse histories. CONCLUSION: Depression, stress, and abuse are well-known
risk factors for suicidal ideation and behavior; however, it has been unclear for
whom, and when, these factors have their greatest impact. These results show that
depression and stress are potent risk factors among those with a history of abuse
and that within-person elevations in these risk factors signal increased short
term risk of suicidal ideation and behavior. (PsycINFO Database Record
PMID- 28425735
TI - Clinician-led, peer-led, and internet-delivered dissonance-based eating disorder
prevention programs: Acute effectiveness of these delivery modalities.
AB - OBJECTIVE: Because independent trials have provided evidence for the efficacy and
effectiveness of the dissonance-based Body Project eating disorder prevention
program, the present trial tested whether clinicians produce the largest
intervention effects, or whether delivery can be task-shifted to less expensive
undergraduate peer educators or to Internet delivery without effect size
attenuation, focusing on acute effects. METHOD: In this study, 680 young women
(Mage = 22.2 years, SD = 7.1) recruited at colleges in 2 states were randomized
to clinician-led Body Project groups, peer-led Body Project groups, the Internet
based eBody Project, or an educational video control condition. RESULTS:
Participants in all 3 variants of the Body Project intervention showed
significantly greater reductions in eating disorder risk factors and symptoms
than did educational video controls. Participants in clinician-led and peer-led
Body Project groups showed significantly greater reductions in risk factors than
did eBody Project participants, but effects for the 2 types of groups were
similar. Eating disorder onset over 7-month follow-up was significantly lower for
peer-led Body Project group participants versus eBody Project participants (2.2%
vs. 8.4%) but did not differ significantly between other conditions. CONCLUSIONS:
The evidence that all 3 dissonance-based prevention programs outperformed an
educational video condition, that both group-based interventions outperformed the
Internet-based intervention in risk factor reductions, and that the peer-led
groups showed lower eating disorder onset over follow-up than did the Internet
based intervention is novel. These acute-effects data suggest that both group
based interventions produce superior eating disorder prevention effects than does
the Internet-based intervention and that delivery can be task-shifted to peer
leaders. (PsycINFO Database Record
PMID- 28425736
TI - Implicit approach and avoidance in patients with obsessive-compulsive disorder.
AB - Avoidance is regarded as an important feature for the development and maintenance
of obsessive-compulsive disorder (OCD) and is usually assessed using explicit
measures such as self-report scales. However, some behavioral schemata are
unavailable to introspection, making them partially inaccessible by explicit
measures. We used an approach-avoidance task (AAT) as an implicit measure to
examine behavioral tendencies in patients with OCD, including patients with
checking- and contamination-related symptoms (n = 63), compared with a healthy
control group (n = 30). Participants were asked to respond to the color of a
stimulus or stimulus frame by pulling a joystick toward themselves or by pushing
it away. The stimuli were comprised of checking-related, contamination-related,
and neutral pictures and words. Patients with contamination-related symptoms were
slower when responding to OCD-related stimuli, independent of approach or
avoidance. Unexpectedly, patients with checking-related symptoms were faster at
pulling (approaching) and slower at pushing (avoiding) checking-related material
compared with neutral stimuli. The slower pushing (avoiding) of checking-related
compared with neutral material correlated positively with explicit ratings of
avoidance. These results suggest a biased approach-avoidance tendency in patients
with checking-related symptoms of OCD, but not in those with contamination
related symptoms of OCD. Future studies are necessary to assess whether the AAT
might be useful in the assessment of treatment gains as well as whether it might
be a training tool to enhance psychotherapeutic changes in OCD. (PsycINFO
Database Record
PMID- 28425738
TI - The link between discrimination and telomere length in African American adults.
AB - OBJECTIVE: Prior work shows that discrimination is associated with a wide array
of negative health outcomes. However, the biological mechanisms through which
this link occurs require more study. We evaluated the association between
discrimination and leukocyte telomere length (LTL; a biological marker of
systemic aging). METHOD: Cross-sectional data were from the Health and Retirement
study, a study of people aged 51+ in the United States, and included 595 African
American males and females. Multiple regression analyses were used to evaluate
whether discrimination was independently associated with LTL. We also considered
the role of potential confounders including sociodemographic factors, health
factors, depressive symptoms, and stress. RESULTS: High discrimination was
associated with shorter LTL after controlling for sociodemographic factors (b =
.034, SE = 0.14, p = .017). This association persisted in analyses that further
adjusted for health factors, depressive symptoms, and stress. CONCLUSION: Results
suggest that discrimination experiences accelerate biological aging in older
African American males and females, alike. This finding helps advance our
understanding of how discrimination generates greater disease vulnerability and
premature death in African Americans. (PsycINFO Database Record
PMID- 28425737
TI - Time-varying and time-invariant dimensions of depression in children and
adolescents: Implications for cross-informant agreement.
AB - The longitudinal structure of depression in children and adolescents was examined
by applying a Trait-State-Occasion structural equation model to 4 waves of self,
teacher, peer, and parent reports in 2 age groups (9 to 13 and 13 to 16 years
old). Analyses revealed that the depression latent variable consisted of 2
longitudinal factors: a time-invariant dimension that was completely stable over
time and a time-varying dimension that was not perfectly stable over time.
Different sources of information were differentially sensitive to these 2
dimensions. Among adolescents, self- and parent reports better reflected the time
invariant aspects. For children and adolescents, peer and teacher reports better
reflected the time-varying aspects. Relatively high cross-informant agreement
emerged for the time-invariant dimension in both children and adolescents. Cross
informant agreement for the time-varying dimension was high for adolescents but
very low for children. Implications emerge for theoretical models of depression
and for its measurement, especially when attempting to predict changes in
depression in the context of longitudinal studies. (PsycINFO Database Record
PMID- 28425740
TI - "Healthier than thou? 'Practicing what you preach' backfires by increasing
anticipated devaluation": Correction to Howe and Monin (2017).
AB - Reports an error in "Healthier Than Thou? "Practicing What You Preach" Backfires
by Increasing Anticipated Devaluation" by Lauren C. Howe and Benoit Monin
(Journal of Personality and Social Psychology, Advanced Online Publication, Feb
27, 2017, np). In the article, the beginning phrase of the second paragraph of
the Internal Meta-Analysis of Studies 3 Through 5 section is incorrect. It should
instead begin as follows: Across the three studies. The Monin et al. (2014)
reference in both the References list and in text is included in error. The
correct citation should read as follows: Monin, B., & Oppenheimer, D. M. (2014).
The limits of direct replications and the virtues of stimulus sampling:
Commentary on Klein et al., 2014. Social Psychology, 45, 299-300. (The following
abstract of the original article appeared in record 2017-08697-001.) Should
experts always practice what they preach? When an expert displays exemplary
behavior, individuals who fear negative devaluation sometimes anticipate that
this expert will look down on them. As a result, displays of excellence can
paradoxically turn off the very people they are trying to inspire. Five studies
document this in the medical domain, showing that individuals who are overweight
or obese and concerned about their weight avoid physicians who advertise their
fitness, for fear that these doctors will judge them negatively. People
(erroneously) believe that doctors have healthier habits than other individuals
(Study 1), doctors advertise healthy habits (Study 2), and overweight individuals
anticipate devaluation from, and thus avoid and feel less comfortable with,
doctors who portray themselves as fitness-focused (Study 3). Studies 4 and 5 test
strategies for physicians to emphasize their own fitness without turning off
weight-sensitive patients. This work demonstrates that it is critical to take
into account ego-defensive processes when attempting to lead by example.
(PsycINFO Database Record
PMID- 28425739
TI - Sleep duration partially accounts for race differences in diurnal cortisol
dynamics.
AB - OBJECTIVE: Emerging research demonstrates race differences in diurnal cortisol
slope, an indicator of hypothalamic-pituitary-adrenocortical (HPA)-axis
functioning associated with morbidity and mortality, with African Americans
showing flatter diurnal slopes than their White counterparts. Sleep
characteristics are associated with both race and with HPA-axis functioning. The
present report examines whether sleep duration may account for race differences
in cortisol dynamics. METHOD: Participants were 424 employed African American and
White adults (mean age = 42.8 years, 84.2% White, 53.6% female) with no
cardiovascular disease (Adult Health and Behavior Project-Phase 2 [AHAB-II]
cohort, University of Pittsburgh). Cortisol slope was calculated using 4 salivary
cortisol readings, averaged over each of 4 days. Demographic (age, sex),
psychosocial (socioeconomic status [SES], affect, discrimination), and health
behaviors (smoking, alcohol use, physical activity) variables were used as
covariates, and sleep (self-report and accelerometry) was also assessed. RESULTS:
African Americans had flatter slopes than Whites (F(1, 411) = 10.45, B = .02, p =
.001) in models adjusting for demographic, psychosocial, and health behavior
covariates. Shorter actigraphy-assessed total sleep time was a second significant
predictor of flatter cortisol slopes (F(1, 411) = 25.27, B = -.0002, p < .0001).
Total sleep time partially accounted for the relationship between race and
diurnal slope [confidence interval = .05 (lower = .014, upper .04)]. CONCLUSIONS:
African Americans have flatter diurnal cortisol slopes than their White
counterparts, an effect that may be partially attributable to race differences in
nightly sleep duration. Sleep parameters should be considered in further research
on race and cortisol. (PsycINFO Database Record
PMID- 28425741
TI - Development of identity clarity and content in adulthood.
AB - The current research examines self-concept clarity over 2 assessment points with
the aims of establishing patterns of stability and change in self-concept clarity
across adulthood, modeling corollary changes in traits and health-related role
limitations, and demonstrating the ways in which gender and age moderate these
patterns. Within this sample of 461 adults age 19-86 years of age, self-concept
clarity had robust rank-order stability and no significant mean-level change
during a 3-year assessment window. However, significant interindividual
variability was present in the developmental patterns of self-concept clarity
over time. These individual differences in development of self-concept clarity
corresponded to developmental patterns in Big Five personality traits and health
related role limitations. Results of this 2 wave longitudinal study suggest 3
primary conclusions: (a) self-concept clarity predicts and corresponds to trait
maturation over time, (b) decreasing self-concept clarity corresponds to
increasing role limitations, and (c) these effects are somewhat contingent on
gender and age. Results are discussed in reference to the maturation of identity
content and metacognitive identity evaluation over the life span. (PsycINFO
Database Record
PMID- 28425743
TI - I'm not the person I used to be: The self and autobiographical memories of
immoral actions.
AB - People maintain a positive identity in at least two ways: They evaluate
themselves more favorably than other people, and they judge themselves to be
better now than they were in the past. Both strategies rely on autobiographical
memories. The authors investigate the role of autobiographical memories of lying
and emotional harm in maintaining a positive identity. For memories of lying to
or emotionally harming others, participants judge their own actions as less
morally wrong and less negative than those in which other people lied to or
emotionally harmed them. Furthermore, people judge those actions that happened
further in the past to be more morally wrong than those that happened more
recently. Finally, for periods of the past when they believed that they were very
different people than they are now, participants judge their actions to be more
morally wrong and more negative than those actions from periods of their pasts
when they believed that they were very similar to who they are now. The authors
discuss these findings in relation to theories about the function of
autobiographical memory and moral cognition in constructing and perceiving the
self over time. (PsycINFO Database Record
PMID- 28425742
TI - Comparing and validating methods of reading instruction using behavioural and
neural findings in an artificial orthography.
AB - There is strong scientific consensus that emphasizing print-to-sound
relationships is critical when learning to read alphabetic languages.
Nevertheless, reading instruction varies across English-speaking countries, from
intensive phonic training to multicuing environments that teach sound- and
meaning-based strategies. We sought to understand the behavioral and neural
consequences of these differences in relative emphasis. We taught 24 English
speaking adults to read 2 sets of 24 novel words (e.g., /buv/, /sig/), written in
2 different unfamiliar orthographies. Following pretraining on oral vocabulary,
participants learned to read the novel words over 8 days. Training in 1 language
was biased toward print-to-sound mappings while training in the other language
was biased toward print-to-meaning mappings. Results showed striking benefits of
print-sound training on reading aloud, generalization, and comprehension of
single words. Univariate analyses of fMRI data collected at the end of training
showed that print-meaning relative to print-sound relative training increased
neural effort in dorsal pathway regions involved in reading aloud. Conversely,
activity in ventral pathway brain regions involved in reading comprehension was
no different following print-meaning versus print-sound training. Multivariate
analyses validated our artificial language approach, showing high similarity
between the spatial distribution of fMRI activity during artificial and English
word reading. Our results suggest that early literacy education should focus on
the systematicities present in print-to-sound relationships in alphabetic
languages, rather than teaching meaning-based strategies, in order to enhance
both reading aloud and comprehension of written words. (PsycINFO Database Record
PMID- 28425744
TI - Once a frog-lover, always a frog-lover?: Infants' goal generalization is
influenced by the nature of accompanying speech.
AB - The ability to interpret choices as enduring preferences that generalize beyond
the immediate situation gives adults a powerful means of predicting and
explaining others' behavior. How do infants come to recognize that current
choices can be driven by generalizable preferences? Although infants can encode
others' actions in terms of goals (Woodward, 1998), there is evidence that 10
month-olds still fail to generalize goal information presented in one environment
to an event sequence occurring in a new environment (Sommerville & Crane, 2009).
Are there some circumstances in which infants interpret others' goals as
generalizable across environments? We investigate whether the vocalizations a
person produces while selecting an object in one room influences infants'
generalization of the goal to a new room. Ten-month-olds did not spontaneously
generalize the actor's goal, but did generalize the actor's goal when the actor
initially accompanied her object selection with a statement of preference.
Infants' generalization was not driven by the attention-grabbing features of the
statement or the mere use of language, as they did not generalize when the actor
used matched nonspeech vocalizations or sung speech. Infants interpreted the goal
as person-specific, as they did not generalize the choice to a new actor. We
suggest that the referential specificity of accompanying speech vocalizations
influences infants' tendency to interpret a choice as personal rather than
situational. (PsycINFO Database Record
PMID- 28425745
TI - When good is stickier than bad: Understanding gain/loss asymmetries in sequential
framing effects.
AB - Considerable research has demonstrated the power of the current positive or
negative frame to shape people's current judgments. But humans must often learn
about positive and negative information as they encounter that information
sequentially over time. It is therefore crucial to consider the potential
importance of sequencing when developing an understanding of how humans think
about valenced information. Indeed, recent work looking at sequentially
encountered frames suggests that some frames can linger outside the context in
which they are first encountered, sticking in the mind so that subsequent frames
have a muted effect. The present research builds a comprehensive account of
sequential framing effects in both the loss and the gain domains. After seeing
information about a potential gain or loss framed in positive terms or negative
terms, participants saw the same issue reframed in the opposing way. Across 5
studies and 1566 participants, we find accumulating evidence for the notion that
in the gain domain, positive frames are stickier than negative frames for novel
but not familiar scenarios, whereas in the loss domain, negative frames are
always stickier than positive frames. Integrating regulatory focus theory with
the literatures on negativity dominance and positivity offset, we develop a new
and comprehensive account of sequential framing effects that emphasizes the
adaptive value of positivity and negativity biases in specific contexts. Our
findings highlight the fact that research conducted solely in the loss domain
risks painting an incomplete and oversimplified picture of human bias and suggest
new directions for future research. (PsycINFO Database Record
PMID- 28425746
TI - Look on the bright side: Positivity bias modulates interference effects in the
simon task.
AB - Negative faces are detected more quickly but categorized more slowly than
positive faces. Using a Simon task, we examined stimulus- and response-related
processes of this dissociation: If negative stimuli are both processed and
responded to more quickly than positive ones, they should elicit reduced Simon
effects. Conversely, if negative stimuli are processed more quickly but responded
to more slowly, enlarged Simon effects should occur. Consistent with the first
possibility, negative stimuli showed reduced Simon effects. Unexpectedly, this
reduction transferred to neutral stimuli (arrows and pointing hands) requiring
the same response as negative faces. This pattern suggests that spatial attention
became biased toward the side associated with a positive-face response and away
from the side associated with a negative-face response, demonstrating that,
similar to higher level cognitive decision processes, even early attentional
processes can be subject to a positivity bias ("Pollyanna effect"). (PsycINFO
Database Record
PMID- 28425747
TI - Early change in coping strategies in responsive treatments for borderline
personality disorder: A mediation analysis.
AB - BACKGROUND: Difficulty in emotion regulation is a hallmark feature of patients
with borderline personality disorder (BPD). Therefore, change in the frequency of
certain patients' coping strategies-aiming at emotion regulation-are among the
most promising mechanisms of change in treatments for BPD. In parallel, it was
highlighted that therapist responsiveness significantly contributed to outcome
across treatment approaches (Stiles, 2009). Based on a randomized controlled
trial (Kramer et al., 2014), the present process-outcome mediation analysis aims
at examining the patient's early change in frequency of coping strategies-in
particular the decrease in behavioral forms of coping-as potential mechanism of
change in responsive treatments for BPD. METHOD: A total of 57 patients with BPD
were included in the present analysis, out of whom 27 were randomly assigned to a
10-session psychiatric treatment and 30 to a 10-session psychiatric treatment
augmented with the responsive intervention of the motive-oriented therapeutic
relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were
transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et
al., 2005; 171 sessions analyzed in total), a validated observer-rated method for
assessing coping strategies in the therapy process. Psychological distress was
assessed using the OQ-45 at intake, after Session 5, and after Session 10.
RESULTS: The results confirmed a responsiveness effect associated with the motive
oriented therapeutic relationship and showed a significant decrease in frequency
of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not
different between the 2 conditions. In addition, we demonstrated that the early
decrease in behavioral forms of coping between Sessions 1 and 5 partially
mediated the link between the group assignment and the change in psychological
distress between Sessions 5 and 10. CONCLUSIONS: These results shed light on the
centrality of therapist responsiveness in treatments for BPD and its impact on
very early change in patient's in-session behavioral coping strategies,
contributing to the effectiveness of short-term treatments for BPD. (PsycINFO
Database Record
PMID- 28425748
TI - A field analysis trial comparing the turnaround times of routine and STAT red
blood cell immunohematology testing.
AB - CONCLUSIONS: The turnaround time (TAT) for pre-transfusion testing is important
for prompt clinical decision-making. TAT includes the time between the arrival of
the sample and the initiation of testing, plus the processing time (PT) required
to generate and report a result. The TAT in larger blood banks is mostly
dependent upon the capability of the analyzer used. In smaller blood banks, where
manual work is often performed, the TAT is dependent on availability and
experience of staff, testing resources, and workload. Our site performed a
comparative analysis of the ORTHO VISION(r) (Ortho Clinical Diagnostics, Raritan,
NJ) and the Echo(r) (Immucor, Norcross, GA) blood bank analyzers, using the TAT
and PT of standard blood bank tests as the outcome metrics. Tests were run in
various combinations to reflect the standard workflow of a busy hospital
transfusion service and under routine and immediate or STAT conditions. We also
compared manual versus automated processing TATs for a variety of pre-transfusion
tests and antibody titers. We found that the capacity of the VISION to load and
run new samples, even while several other tests were ongoing, allowed for faster
overall TAT when compared with samples run on the Echo. The PTs of the two
analyzers (from load to result) were also compared, and we found them to be
equivalent. These findings highlight the inherent flaw in considering only PT
when assessing a laboratory's ability to efficiently and consistently make
results available to best meet customer and patient needs. In addition, we
observed a tighter distribution of TATs and PTs when the VISION was compared with
the Echo analyzer, providing a higher level of predictability for availability of
results. Finally, when compared with manual antibody titer testing, the VISION
analyzer showed a faster PT.
PMID- 28425749
TI - Hemolytic transfusion reaction attributable to anti-Dia.
AB - CONCLUSIONS: In situations when a patient's antibody detection test is negative,
many institutions have moved from an indirect antiglobulin test (IAT) crossmatch
to an electronic crossmatch system. Here we report a case of an acute hemolytic
transfusion reaction attributable to anti-Dia in a patient with a negative
antibody detection test. A 22-year-old female patient with a diagnosis of beta
thalassemia and sickle cell anemia commenced a routine exchange transfusion of 5
units of red blood cells (RBCs) in the apheresis unit as part of her regular
treatment. When the patient started receiving the implicated unit, she reported
back pain, chest pain, and a feeling of anxiety, suggestive of an acute
transfusion reaction. The transfusion was ceased and an investigation of an
adverse event was commenced. This case illustrates that the presence of
antibodies to low-prevalence antigens remains a significant issue for transfusion
dependent individuals. To prevent other transfusion reactions by anti-Dia, the
addition of Di(a+) cells to the reagent RBCs used for the antibody detection test
along with IAT-crossmatching of donor units for all patients with sickle cell
disease is recommended.
PMID- 28425750
TI - Modeling alloantibody formation to high-incidence red blood cell antigens in
immune responders using genotypic data.
AB - CONCLUSIONS: Alloimmunization to red blood cell antigens is unpredictable and
poorly understood. Patients who are negative for high-incidence antigens (HIAs)
are at risk for developing the corresponding antibodies. Molecular methods can
easily predict the lack of an antigen and thus, the risk of an individual to
become immunized. We examined the prevalence and risk factors for HIA
alloimmunization in patients at risk based on genotyping results. Genotyping
using a molecular method (HEA BeadChipTM, Immucor, Warren, NJ) was performed on
all patient specimens referred for molecular testing over 45 months; serologic
and clinical data were analyzed. We used simple and multiple logistic regression
to model the risk factors for alloimmunization to an HIA. Of the 2591 patients
genotyped, 32 (1.2%) were homozygous for at least one variant predicting absence
of an HIA. Of these 32 patients, prior transfusion or pregnancy history was
available for 29 (91%). Four susceptible patients made an antibody to an HIA
(12.5% of all, 13.8% of those with a documented exposure). Two of these four
patients (50%) had made an alloantibody to another antigen. The odds of forming
an antibody to an HIA were not related to the total number of transfusions (p =
0.47), the total number of alloantibodies (p = 0.61), or diagnosis of sickle cell
disease (p = 0.77) in simple logistic regression. Adjustment for the other two
variables in a multiple logistic regression was also not significant for each
variable (p = 0.6, p = 0.7, and p = 0.7, respectively). Although they had a known
exposure to alloantigens through transfusion or pregnancy, 86.2 percent of
patients (25 of 29) at risk for alloantibody formation to an HIA in fact did not
mount an immune response to that antigen. Possible risk factors including the
number of transfused units or the total number of alloantibodies made were not
predictors of making an alloantibody to an HIA in our sampling. Our results
suggest that other patient-specific risk factors for alloimmunization exist.
PMID- 28425751
TI - Development of red blood cell autoantibodies following treatment with checkpoint
inhibitors: a new class of anti-neoplastic, immunotherapeutic agents associated
with immune dysregulation.
AB - CONCLUSIONS: Ipilimumab, nivolumab, and pembrolizumab represent a new class of
immunotherapeutic drugs for treating patients with advanced cancer. Known as
checkpoint inhibitors, these drugs act to upregulate the cellular and humoral
immune response to tumor antigens by inhibiting T-cell autoregulation. As a
consequence, they can be associated with immune-related adverse events (irAEs)
due to loss of self-tolerance, including rare cases of immune-related cytopenias.
We performed a retrospective clinical chart review, including serologic,
hematology, and chemistry laboratory results, of two patients who developed red
blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor.
Serologic testing of blood samples from these patients during induction therapy
with ipilimumab and nivolumab, respectively, showed their RBCs to be positive by
the direct antiglobulin test (IgG+, C3+) and their plasma to contain panreactive
RBC autoantibodies. Neither patient had evidence of hemolysis. Both patients
developed an additional irAE during treatment. A literature review for patients
who had developed immune-mediated cytopenia following treatment with a checkpoint
inhibitor was performed. Nine other patients were reported with a hematologic
irAE, including six with anemia attributable to autoimmune anemia, aplastic
anemia, or pure RBC aplasia. Hematologic irAEs tend to occur early during
induction therapy, often coincident with irAEs of other organs. In conclusion,
checkpoint inhibitors can be associated with the development of autoantibodies,
immune-mediated cytopenias, pure RBC aplasia, and aplastic anemia.
Immunohematology reference laboratories should be aware of these agents when
evaluating patients with advanced cancer and new-onset autoantibodies, anemia,
and other cytopenias.
PMID- 28425752
TI - Use of standard laboratory methods to obviate routine dithiothreitol treatment of
blood samples with daratumumab interference.
AB - CONCLUSIONS: Daratumumab is an antibody currently used in the treatment of
patients with refractory multiple myeloma. Blood samples from patients being
treated with daratumumab may show panreactivity during pre-transfusion testing.
To facilitate the provision of blood components for such patients, it is
recommended that a baseline phenotype or genotype be established prior to
starting treatment with daratumumab. If patient red blood cells (RBCs) require
phenotyping after the start of daratumumab treatment, dithiothreitol (DTT)
treatment of the patient's RBCs should be performed. The medical charts of four
patients treated with daratumumab were reviewed. The individual number of doses
ranged from 1 to 14; patient age ranged from 55 to 78 years; two men and two
women were included in the review. Type and screen data were obtained from
samples collected over 33 encounters with a range of 1 to 13 encounters per
patient. All samples were tested initially by automated solid-phase testing. Any
reactivity with solid phase led to tube testing with either low-ionic-strength
saline, polyethylene glycol, or both. If incubation failed to eliminate the
reactivity, the sample was sent to a reference laboratory for DTT treatment and
phenotyping. Of the 33 samples tested, 23 (69.7%) samples had reactivity in solid
phase testing. In 8 of the 10 samples that did not react in solid-phase, testing
was conducted more than four half-lives after the last dose of daratumumab. Of
the 23 that had reactivity in solid-phase, 16 (69.6%) samples demonstrated loss
of reactivity using common laboratory methods. For the seven patients whose
sample reactivity was not initially eliminated, six were provided with
phenotypically matched blood based on prior molecular testing. Only one sample
was sent out for DTT treatment. These results suggest that daratumumab
interference with pre-transfusion testing can be addressed using common
laboratory methods. This finding could save time and money for laboratories that
do not have DTT available.
PMID- 28425753
TI - Applications of selected cells in immunohematology in a developing country: case
studies.
AB - CONCLUSIONS: When an antibody is detected, its specificity should be determined
and its likely clinical significance should be assessed. When one antibody has
been identified, it becomes necessary to confirm the presence of additional
significant antibodies to ensure that compatible blood is provided to the
patient. To perform this confirmation, specific reagent red blood cells (RBCs)
are selected; these are called selected cells. Though the most common use of
selected cells is for antibody confirmation, they can also be used for several
other immunohematologic applications. In a developing country like India, the
performance of antibody screening for unexpected antibodies on a routine basis is
a comparatively new phenomenon, and those laboratories performing advanced
immunohematologic testing would need to use selected cells to arrive at an
accurate conclusion. This report defines selected cells and enumerates sources of
these RBCs. Detailed immunohematologic applications are discussed with applicable
case studies.
PMID- 28425755
TI - Thrombus aspiration in acute coronary syndromes: prevalence, procedural success,
change in serial troponin T levels and clinical outcomes in a contemporary Swiss
cohort.
AB - BACKGROUND: Randomised controlled trials have provided conflicting results
regarding procedural and clinical outcomes of thrombus aspiration combined with
percutaneous coronary intervention, when compared with primary percutaneous
coronary intervention alone in patients with acute coronary syndromes. METHODS:
Acute coronary syndrome patients referred for coronary angiography to four Swiss
university hospitals between 2009 and 2012 were enrolled in the SPUM-ACS cohort.
At the discretion of the interventional cardiologist, patients underwent thrombus
aspiration with percutaneous coronary intervention or percutaneous coronary
intervention alone. Procedural success was defined as post-procedural
thrombolysis in myocardial infarction III flow in the infarct-related artery.
Serial changes in high-sensitivity troponin T (DeltahsTnT) and adjudicated 30
days (1 year) clinical events defined as the composite of cardiac death,
recurrent myocardial infarction or clinically indicated coronary
revascularisation were assessed. RESULTS: Among 1641 patients, 777 (47.4%) had
angiographic evidence of coronary thrombus. Patients were categorised into
thrombus aspiration with percutaneous coronary intervention ( n=663) or
percutaneous coronary intervention alone ( n=114). ST-segment elevation
myocardial infarction (STEMI) patients more often received thrombus aspiration
with percutaneous coronary intervention (87.8%) than non-STEMI patients (73.5%),
P<0.001. Procedural success was not different in thrombus aspiration with
percutaneous coronary intervention compared with percutaneous coronary
intervention alone (93.8% vs. 90.7%, P=0.243). DeltahsTnT was similar in STEMI
patients (3.09+/-4.52 vs. 2.19+/-4.92 ug/l, P=0.086) as was clinical outcome in
the entire cohort at 30 days (2.9% vs. 3.6%, P=0.76) and 1 year (7.2% vs. 5.3%,
P=0.55) regardless of whether thrombus aspiration was used during primary
percutaneous coronary intervention or not. CONCLUSIONS: In this real-world acute
coronary syndrome cohort, patients treated by thrombus aspiration with
percutaneous coronary intervention showed no difference in the restoration of
coronary blood flow compared with percutaneous coronary intervention alone
immediately after the procedure. Furthermore, DeltahsTnT and clinical outcomes at
either 30 days or 1 year were similar between thrombus aspiration with
percutaneous coronary intervention or percutaneous coronary intervention alone.
CLINICAL TRIALS REGISTRATION: SPUM-ACS cohort NCT01000701.
PMID- 28425754
TI - Immunotherapy and targeted therapy in brain metastases: emerging options in
precision medicine.
AB - Brain metastases (BM) continue to represent an unmet clinical need in oncology.
Immunotherapy and targeted therapy hold great promise in the treatment of BM.
Emerging data are confirming the activity of these agents in patients with BM.
Genomic studies have confirmed that clinically actionable mutations are present
in BM and they can be used in clinical studies to link targeted therapies with
their genetic targets. Furthermore, as molecular signatures associated with
sensitivity and resistance to immunotherapies are developed, we will better be
able to select BM patients who will most benefit from these therapies.
Understanding the genetic and immune evolution within BM should drive the next
generation of immunotherapy and target therapy, as well as increase the accuracy
of the selection process for these therapies.
PMID- 28425756
TI - CNS hemangioblastomatosis in a patient without von Hippel-Lindau disease.
AB - We report on a case of disseminated CNS hemangioblastoma, also referred to as
hemangioblastomatosis, involving the supratentorial compartment and the entire
spine. The patient presented with new onset headache, gait difficulties and
memory deficits many years following resection of a hemangioblastoma from the
cerebellum. The patient's family history was negative for von Hippel-Lindau (VHL)
disease, and his personal history was negative for any additional VHL-defining
lesions. Imaging revealed extensive dural caking and nodularity both
supratentorially and in the spine, along with scattered parenchymal tumors
showing a more typical appearance for hemangioblastoma. Biopsy of the dural
thickening revealed histologic features compatible with hemangioblastoma. Genetic
testing for VHL was eventually completed, and no evidence of a germline VHL
mutation was detected.
PMID- 28425757
TI - The prevalence and characteristics of a subcortical cystic lesion at the
subspinous region of the knee.
AB - Background Although we observed that subcortical cysts near the attachment of the
meniscus or cruciate ligaments are frequently seen with a tear or degeneration of
the adjacent meniscus and/or cruciate ligament, there is no large study
describing the prevalence, distribution, and associated findings of these cysts.
Purpose To evaluate the prevalence and distribution of subcortical cysts near the
attachments of the meniscus or cruciate ligaments and evaluate pathologies of the
meniscus or cruciate ligaments using magnetic resonance imaging (MRI). Material
and Methods We reviewed 1009 knee MRIs for the presence of subcortical cysts near
the meniscus or cruciate ligament attachments and evaluated their size, location,
edema of the adjacent bone marrow, and integrities of the medial and lateral
meniscus and anterior and posterior cruciate ligaments. Results The 110 cysts
were found in either the middle (n = 56), posterior (n = 52), or anterior (n = 2)
subspinous regions. Sixty-two were at meniscal root insertion, including seven at
the lateral meniscus anterior horn, five at the lateral meniscus posterior horn,
48 at the medial meniscus posterior horn, and two at the medial meniscus anterior
horn. All were associated with an adjacent meniscal pathology. Of the 34 cysts at
the anterior cruciate ligament (ACL) insertion, 28 had ACL pathology. Nine cysts
had surrounding edema in the adjacent bone marrow. Conclusion Subcortical cysts
at the subspinous region of the knee were seen in 9.6% of knee MRI examinations.
Most were in close proximity to the meniscal or cruciate ligaments with
associated pathologies, suggesting that abnormal stress on the bone induces cyst
formation.
PMID- 28425758
TI - Agreement between MRI and pathologic analyses for determination of tumor size and
correlation with immunohistochemical factors of invasive breast carcinoma.
AB - Background There may be discordance between tumor size determined by magnetic
resonance imaging (MRI) and that observed during pathologic analyses. Purpose To
evaluate MRI-pathology concordance of tumor size in patients with invasive breast
carcinoma. Material and Methods Data from 307 invasive breast carcinomas were
analyzed retrospectively. Preoperative breast MRI was reviewed for size, lesion
type, morphology, and dynamic contrast-enhanced tumor kinetics. MRI tumor size
was compared with tumor size measurements from the pathologic analysis.
Concordance was defined as a difference in diameter of <= 0.5 cm. MRI-pathology
concordance was compared according to clinical and histopathologic features.
Results The mean tumor size on MRI was 2.48 +/- 1.41 cm. Tumor measurements
determined by MRI were not significantly different from those recorded in the
pathologic reports (2.56 +/- 1.61 cm, P = 0.199). MRI-pathology concordance was
found in 229/307 (74.6%) cases; the size was overestimated in 36 (11.7%) tumors
and underestimated in 42 (13.7%). On univariate analysis, MRI-pathology
discordance was associated with larger tumor size ( P < 0.001), estrogen receptor
(ER) negativity ( P = 0.006), and lymphovascular invasion ( P = 0.003). Human
epidermal growth factor receptor 2 positive molecular subtype showed worse
correlation between the tumor size measured by MRI and pathology compared with
luminal A and luminal B subtypes ( P = 0.008 and 0.007). On multivariate
analysis, tumor size and ER status significantly influenced MRI-pathology
concordance ( P < 0.05). Conclusion ER negativity and larger tumor size were
strongly associated with MRI-pathology discordance in invasive breast carcinomas.
Awareness of these factors might improve surgical planning.
PMID- 28425759
TI - Speech pathology as the MasterChef: Getting the right ingredients and stirring
the pot.
AB - The purpose of this paper is to consider the many influences that have an impact
on appropriate speech-language pathology service delivery. The competitive
cooking and entertainment television program, MasterChef, is used as an analogy
to consider the ingredients, blend and approach required to improve speech
language pathology services. Speech-language pathologists (SLPs) enter the
profession with the aim of assisting those with communication and swallowing
disorders to have a better quality of life. Thus, we should be restless to
continue to improve our services in order to achieve the best influence and
outcomes by changing our recipes and ingredients. However, having good technical
skills as a SLP is not sufficient in ensuring that the services are the best they
can be. We have to consider available resources, customers and service users, who
it is that judges our services, whether we are as good as we could or should be,
what can help us improve our services, what the appetite is for our services, and
how we incorporate evidence-based practice. This paper considers the value of
understanding and using information on incidence and prevalence, evidence-based
practice and outcome measurement. Blending technical, clinical and academic
abilities with personal skills will result in an award-winning menu.
PMID- 28425760
TI - Polar-phase indices of perioral muscle reciprocity during syllable production in
Parkinson's disease.
AB - PURPOSE: This research characterised perioral muscle reciprocity and amplitude
ratio in lower lip during bilabial syllable production [pa] at three rates to
understand the neuromotor dynamics and scaling of motor speech patterns in
individuals with Parkinson's disease (PD). METHOD: Electromyographic (EMG)
signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI]
and depressor labii inferioris [DLI] were recorded during syllable production and
expressed as polar-phase notations. RESULT: PD participants exhibited the general
features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG
during syllable production. The control group showed significantly higher
integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants.
No speech rate effects were found in EMG muscle reciprocity and amplitude
magnitude across all muscle pairs. CONCLUSION: Similar patterns of muscle
reciprocity in PD and controls suggest that corticomotoneuronal output to the
facial nucleus and respective perioral muscles is relatively well-preserved in
our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio
among PD participants is consistent with the putative reduction in the
thalamocortical activation characteristic of this disease which limits motor
cortex drive from generating appropriate commands which contributes to
bradykinesia and hypokinesia of the orofacial mechanism.
PMID- 28425761
TI - Adult pilocytic astrocytoma of conus medullaris: clinical considerations and
review of the literature.
AB - Astrocytomas are responsible for 30% of all primitive intramedullary tumors with
cervicothoracic predominance. However, only about one hundred cases of
intramedullary pilocytic astrocytomas were described. The authors described the
case of a 69 year-old patient presenting with a broad-base gait, bilateral pain
and dysesthesia of inferior limbs with a diagnosis of an intra-axial cystic
lesion centered to the conus medullaris, diagnosed as pilocytic astrocytoma of
conus medullaris (PACM) after surgery. To the best of our knowledge, only two
previous reports concerning PACM were made. As benign lesions associated with
long survivals, function should be the mainstay of treatment of PACM. Surgical
resection should be performed. Adjuvant radiotherapy or chemotherapy has no
establish role in pilocytic astrocytic lesions.
PMID- 28425762
TI - The evaluation of bulbar dysfunction in amyotrophic lateral sclerosis: survey of
clinical practice patterns in the United States.
AB - OBJECTIVE: Speech and swallowing impairments are highly prevalent in individuals
with amyotrophic lateral sclerosis (ALS) and contribute to reduced quality of
life, malnutrition, aspiration, pneumonia and death. Established practice
parameters for bulbar dysfunction in ALS do not currently exist. The aim of this
study was to identify current practice patterns for the evaluation of speech and
swallowing function within participating Northeast ALS clinics in the United
States. METHODS AND RESULTS: A 15-item survey was emailed to all registered NEALS
centres. Thirty-eight sites completed the survey. The majority (92%) offered
Speech-Language Pathology, augmentative and alternative communication (71%), and
dietician (92%) health care services. The ALS Functional Rating Scale-Revised and
body weight represented the only parameters routinely collected in greater then
90% of responding sites. Referral for modified barium swallow study was routinely
utilised in only 27% of sites and the use of percutaneous gastrostomy tubes in
ALS patient care was found to vary considerably. CONCLUSIONS: This survey reveals
significant variability and inconsistency in the management of bulbar dysfunction
in ALS across NEALS sites. We conclude that a great need exists for the
development of bulbar practice guidelines in ALS clinical care to accurately
detect and monitor bulbar dysfunction.
PMID- 28425764
TI - BRAF-V600E mutant papillary craniopharyngioma dramatically responds to
combination BRAF and MEK inhibitors.
AB - We present a patient with BRAF-V600E mutant papillary craniopharyngioma
successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and
MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved
refractory to radiation. Serial brain MRIs and PET revealed marked tumor
reduction with gradual neurological improvement and permanent panhypopituitarism.
PMID- 28425765
TI - The prevention and treatment of venous thromboembolism in pregnancy.
AB - INTRODUCTION: Venous thromboembolism (VTE) in pregnancy represents an important
cause of maternal morbidity and mortality in developed countries, with an
incidence of 0.5-2.2 per 1000 pregnancies. In addition to hemostatic changes
occurring during normal pregnancy, several risk factors have been identified.
Thus, a variety of clinical conditions as well as fetal and maternal risks linked
to a possible anticoagulant therapy should be considered for the management of
VTE during pregnancy. Unfortunately, there is a paucity of high-quality evidence
from randomized trials in this field, and current recommendations are based on
observational studies or evidence gathered from studies in the non-pregnant
population. Areas covered: The purpose of this review is to summarize available
evidence on the prevention and treatment of pregnancy-related VTE. Expert
commentary: Although the optimal prophylactic and therapeutic dosage has not yet
been established, low-molecular-weight heparin (LMWH) represents the most
efficacious and safe anticoagulant during pregnancy. Thus, after an accurate risk
stratification of women during pregnancy and puerperium, LMWH should be
recommended to women at risk for VTE and to those ones suffering from an acute
event.
PMID- 28425766
TI - Update in the treatment of non-influenza respiratory virus infection in solid
organ transplant recipients.
AB - INTRODUCTION: Despite the improved outcomes in solid organ transplantation with
regard to prevention of rejection and increased patient and graft survival,
infection remains a common cause of morbidity and mortality. Respiratory viruses
are a frequent and potentially serious cause of infection after solid organ
transplantation. Furthermore, clinical manifestations of respiratory virus
infection (RVI) may be more severe and unusual in solid organ transplant
recipients (SOTRs) compared with the non-immunocompromised population. Areas
covered: This article reviews the non-influenza RVIs that are commonly
encountered in SOTRs. Epidemiologic and clinical characteristics are highlighted
and available treatment options are discussed. Expert opinion: New diagnostic
tools, particularly rapid molecular assays, have expanded the ability to identify
specific RVI pathogens in SOTRs. This is not only useful from a treatment
standpoint but also to guide infection control practices. More data are needed on
RVIs in the solid organ transplant population, particularly regarding their
effect on rejection and graft dysfunction. There is also a need for new antiviral
agents active against these infections as well as markers that can identify which
patients would most benefit from treatment.
PMID- 28425767
TI - Chronic total coronary occlusion: treatment results.
AB - OBJECTIVES: To describe the clinical and procedural coronary chronic total
occlusion (CTO) treatment results in a Nordic PCI centre during the
implementation of a CTO treatment program. DESIGN: In a retrospective registry
study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular
Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart
failure score, (3) lesion complexity and (4) adverse events during hospital stay
and three months following the index procedure. RESULTS: The study cohort
included 503 patients (594 lesions). From 2010 to 2013 96% of procedures were
performed with antegrade wire-escalation technique and 4% performed using
retrograde techniques, from 2013-2016 the corresponding numbers were 83% and
17.0%. The procedural success rate was 69%, increasing from 64% before to 72% (p
= .06) after routinely using the retrograde approach. No individual patient
characteristic, lesion variable or score was strongly associated with procedural
success or failure. There were 4% serious procedure related complications. In
patients with PCI of a CTO lesion only, 87% were in CCS or NYHA functional class
>=2 before the index procedure vs. 22% at follow-up. CONCLUSIONS: Routine use of
retrograde techniques tended to increase the procedural success rate. Clinical
results after three months were acceptable, but the complication rate was higher
than for non-CTO PCI. Individual patient and lesion characteristics had a low
predictability for procedural success. Therefore, clinical symptoms, objective
signs of myocardial ischemia and procedural risk should be focus points in
coronary chronic total occlusion treatment strategies.
PMID- 28425769
TI - Convergent and Divergent Validity Between the KTK and MOT 4-6 Motor Tests in
Early Childhood.
AB - The aim of this study was to investigate the convergent and divergent validity
between the Body Coordination Test for Children (KTK) and the Motor Proficiency
Test for 4- to 6-Year-Old Children (MOT 4-6). A total of 638 children (5-6 yr
old) took part in the study. The results showed a moderately positive association
between the total scores of both tests (rs = .63). Moreover, the KTK total score
correlated more highly with the MOT 4-6 gross motor score than with the MOT 4-6
fine motor score (rs = .62 vs. .32). Levels of agreement were moderate when
identifying children with moderate or severe motor problems and low at best when
detecting children with higher motor-competence levels. This study provides
evidence of convergent and divergent validity between the KTK and MOT 4-6.
However, given the moderate to low levels of agreement, either measurement may
lead to possible categorization errors. Therefore, it is recommended that
children's motor competence not be judged based on the result of a single test.
PMID- 28425770
TI - Measuring Fine Motor Skills in Children with Visual Impairments.
PMID- 28425771
TI - Review of stereotactic radiosurgery for intradural spine tumors.
AB - Stereotactic radiosurgery (SRS) has become an increasingly popular treatment
modality for spinal tumors due to its noninvasive and targeted approach. Whether
SRS has the promise of relieving pretreatment symptoms and providing local tumor
control for patients with intradural spine tumors is still debated. This review
explores the current literature on SRS treatment for both metastatic and benign
intradural tumors, with a focus on differential use for intramedullary and
intradural extramedullary neoplasms. Although mortality rates from underlying
malignant disease remain high, SRS may benefit patients with spinal metastatic
lesions. Benign tumors have shown a promising response to SRS therapy with low
rates of complications. Larger studies are necessary to determine the indications
and outcome profile of SRS for intradural spinal neoplasms.
PMID- 28425772
TI - Prediction of successful dose reduction or discontinuation of adalimumab,
etanercept, or infliximab in rheumatoid arthritis patients using serum drug
levels and antidrug antibody measurement.
AB - BACKGROUND: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug
antibodies (ADAb) can predict successful dose reduction (in patients with high
DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid
arthritis (RA) patients. RESEARCH DESIGN AND METHODS: RA patients that were using
adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing
well, were tapered until discontinuation or flare (1-1.5 year follow up). Random
timed DL for adalimumab and etanercept and trough DL for infliximab were measured
before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut
off DL were determined. RESULTS: No predictive value of adalimumab and infliximab
DL for all outcomes were found, except for an inverse association of lower
etanercept DL and higher chance for successful dose reduction (Area Under the
Curve (AUC) 0.36, 95% CI 0.23-0.49; cut-off <2.6 mg/l). In sub analyses, higher
adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58-1.00;
cut-off >7.8). ADAb were infrequent and not predictive of successful
discontinuation. CONCLUSIONS: No predictive value of baseline adalimumab,
etanercept and infliximab DL or ADAb for successful dose reduction or
discontinuation in RA was found in this context, with the possible exception of
high adalimumab trough levels for successful dose reduction.
PMID- 28425773
TI - Prognostic value of pre- and post-treatment health-related quality of life in
predicting survival of patients with brain metastases.
AB - AIM: The present study aimed to determine the prognostic survival value of
pretreatment health-related quality of life (HRQOL) and changes in HRQOL
following whole-brain radiation treatment in patients with brain metastases.
METHODS: Patients who were treated with whole-brain radiation treatment and
completed HRQOL questionnaires were included. Univariate and multivariate Cox
proportional hazard models of overall survival (OS) were conducted for overall
HRQOL and domain scores. RESULTS & CONCLUSION: Patients with lower HRQOL at
baseline, especially lower physical functioning and motor dysfunction domains,
were more likely to have poorer survival. Changes in overall HRQOL and its
domains were not significantly related to OS. Pretreatment HRQOL, especially
physical functioning and motor dysfunction, has added prognostic value in
patients with brain metastases.
PMID- 28425774
TI - Profile of the triplex assay for detection of chlamydia, gonorrhea and
trichomonas using the BD MAXTM System.
AB - INTRODUCTION: Chlamydia, gonorrhea and trichomonas are the most common curable
STI. improved access to testing could reduce infection rates and prevent
sequelae. nucleic acid amplification tests are the recommend class of diagnostic
assay for these infections which are often asymptomatic. Areas covered: A
description of the BD MAXTM System (MAX) and the BD MAX CT/GC/TV assay is
provided along with data from a large US clinical trial. The capacity of the
system for other tests and for lab developed assays is also described. Expert
commentary: The CT/GC/TV assay on the MAX is a triplex PCR assay suitable for use
with female urine and vaginal or endocervical swab samples. Male urine can be
tested by ordering the CT/GC results but has not yet been evaluated for
trichomonas. The assay performance characteristics are similar to those of assays
run on high-throughput platforms with sensitivity >=91.5% and specificity >=98.6%
for all analytes. Screening with the CT/GC/TV assay can be combined with testing
for vaginitis which would provide a greater depth of coverage for common co
infections. The throughput is moderate (1-48 samples per 8-hour shift) but the
menu includes assays beyond STI pathogens making this a suitable platform for
moderate volume laboratories.
PMID- 28425775
TI - Academic outcomes of multilingual children in Australia.
AB - PURPOSE: The Australian educational system is increasingly challenged to meet the
needs of multilingual students, who comprise a fifth of the student population.
Within the context of a monolingual English curriculum, multilingual children who
enter school not yet English proficient may be at risk of experiencing
inequitable educational outcomes. METHOD: We examined the relationship between
the timing of multilingual children's acquisition of receptive English vocabulary
skills and subsequent reading and numeracy outcomes, as well as factors
associated with earlier versus later timing of acquisition. Data were drawn from
the Kindergarten-cohort (n = 4983) of the Longitudinal Study of Australian
Children - a nationally representative, community sample of Australian children.
RESULT: Linear regression analyses revealed that multilingual children who begin
school with proficient receptive English vocabulary skills, or who acquire
proficiency early in schooling, are indistinguishable from their monolingual
peers in literacy and numeracy outcomes by 10-11 years. However, later
acquisition of receptive English vocabulary skills (i.e. after 6-7 years) was
associated with poorer literacy outcomes. In turn, socioeconomic disadvantage and
broader language or learning problems predicted this later acquisition of
receptive English vocabulary skills. CONCLUSION: All children need to be
supported during the early years of school to reach their full educational
potential.
PMID- 28425776
TI - Development of the Aboriginal Communication Assessment After Brain Injury
(ACAABI): A screening tool for identifying acquired communication disorders in
Aboriginal Australians.
AB - PURPOSE: Acquired communication disorders (ACD), following stroke and traumatic
brain injury, may not be correctly identified in Aboriginal Australians due to a
lack of linguistically and culturally appropriate assessment tools. Within this
paper we explore key issues that were considered in the development of the
Aboriginal Communication Assessment After Brain Injury (ACAABI) - a screening
tool designed to assess the presence of ACD in Aboriginal populations. METHOD: A
literature review and consultation with key stakeholders were undertaken to
explore directions needed to develop a new tool, based on existing tools and
recommendations for future developments. RESULT: The literature searches revealed
no existing screening tool for ACD in these populations, but identified tools in
the areas of cognition and social-emotional wellbeing. Articles retrieved
described details of the content and style of these tools, with recommendations
for the development and administration of a new tool. The findings from the
interview and focus group views were consistent with the approach recommended in
the literature. CONCLUSIONS: There is a need for a screening tool for ACD to be
developed but any tool must be informed by knowledge of Aboriginal language,
culture and community input in order to be acceptable and valid.
PMID- 28425778
TI - Meditation awareness training for the treatment of workaholism: A controlled
trial.
AB - Background and aims Workaholism is a form of behavioral addiction that can lead
to reduced life and job satisfaction, anxiety, depression, burnout, work-family
conflict, and impaired productivity. Given the number of people affected, there
is a need for more targeted workaholism treatments. Findings from previous case
studies successfully utilizing second-generation mindfulness-based interventions
(SG-MBIs) for treating behavioral addiction suggest that SG-MBIs may be suitable
for treating workaholism. This study conducted a controlled trial to investigate
the effects of an SG-MBI known as meditation awareness training (MAT) on
workaholism. Methods Male and female adults suffering from workaholism (n = 73)
were allocated to MAT or a waiting-list control group. Assessments were performed
at pre-, post-, and 3-month follow-up phases. Results MAT participants
demonstrated significant and sustained improvements over control-group
participants in workaholism symptomatology, job satisfaction, work engagement,
work duration, and psychological distress. Furthermore, compared to the control
group, MAT participants demonstrated a significant reduction in hours spent
working but without a decline in job performance. Discussion and conclusions MAT
may be a suitable intervention for treating workaholism. Further controlled
intervention studies investigating the effects of SG-MBIs on workaholism are
warranted.
PMID- 28425777
TI - Self-reported dependence on mobile phones in young adults: A European cross
cultural empirical survey.
AB - Background and aims Despite many positive benefits, mobile phone use can be
associated with harmful and detrimental behaviors. The aim of this study was
twofold: to examine (a) cross-cultural patterns of perceived dependence on mobile
phones in ten European countries, first, grouped in four different regions
(North: Finland and UK; South: Spain and Italy; East: Hungary and Poland; West:
France, Belgium, Germany, and Switzerland), and second by country, and (b) how
socio-demographics, geographic differences, mobile phone usage patterns, and
associated activities predicted this perceived dependence. Methods A sample of
2,775 young adults (aged 18-29 years) were recruited in different European
Universities who participated in an online survey. Measures included socio
demographic variables, patterns of mobile phone use, and the dependence subscale
of a short version of the Problematic Mobile Phone Use Questionnaire (PMPUQ;
Billieux, Van der Linden, & Rochat, 2008). Results The young adults from the
Northern and Southern regions reported the heaviest use of mobile phones, whereas
perceived dependence was less prevalent in the Eastern region. However, the
proportion of highly dependent mobile phone users was more elevated in Belgium,
UK, and France. Regression analysis identified several risk factors for increased
scores on the PMPUQ dependence subscale, namely using mobile phones daily, being
female, engaging in social networking, playing video games, shopping and viewing
TV shows through the Internet, chatting and messaging, and using mobile phones
for downloading-related activities. Discussion and conclusions Self-reported
dependence on mobile phone use is influenced by frequency and specific
application usage.
PMID- 28425779
TI - Prevention paradox logic and problem gambling: Does low-risk gambling impose a
greater burden of harm than high-risk gambling?
AB - Background and aims The aim of this paper is to examine the evidence and
arguments in favor of prevention paradox (PP) logic in the context of problem
gambling. Evidence from recent studies of gambling and the distribution of harm
across lower and higher risk gamblers is reviewed to examine the contention that
the absolute burden of harm is greater in low-risk (LR) gamblers than the problem
gamblers. Methods The review examines a number of methodological and conceptual
concerns about existing evidence in support of the PP. Results The principal
problems identified include the misclassification of LR gamblers; the use of
binary scoring method that understates the frequency of harms in high-risk
populations; a tendency to confuse behavior and harm; and the use of potentially
overly inclusive definitions of harm with low thresholds of severity. Discussion
and conclusions This paper makes a number of recommendations for enhancement of
this area of research, including the use of clear definitions of harm and LR
behavior and a greater focus on harm with material impacts on people's quality of
life.
PMID- 28425780
TI - Endothelium-dependent Vasodilation in Hypertension: A Review.
AB - Using both in vitro and in vivo techniques, it has repeatedly been shown that
endothelium-dependent vasodilation (EDV) is impaired in different forms of
experimental hypertension (SHR, Dahl salt-sensitive rat, DOCA-salt rat and
renovascular hypertension). EDV has also been found to be impaired in primary, as
well as in secondary forms of human hypertension. Although impaired EDV is a
general finding in hypertension, the pathophysiological mechanisms might differ
between different forms of hypertension and between different types of vessels
and vascular beds. Impaired activity of nitric oxide synthase, increased release
of endothelin-1, increased production of a prostanoid-derived contracting factor,
decreased generation of endothelium-derived hyperpolarizing factor/s and
impairment caused by superoxide ions have all been shown to contribute to the
impairment of EDV during different conditions. While most antihypertensive
treatments improve EDV in experimental hypertension, no uniform picture has been
seen in human hypertension, possibly because different antihypertensive drugs
have different direct actions on EDV. This review shows that while impaired EDV
has been found to be a general feature of hypertension, the mechanisms involved
and the therapeutic opportunities have still to be established.
PMID- 28425781
TI - Endothelial Dysfunction - A Challenge for Hypertension Research.
PMID- 28425782
TI - Cerebral Perfusion in Hypertensives with Carotid Artery Stenosis: A Comparative
Study of Lacidipine and Hydrochlorothiazide.
PMID- 28425783
TI - Effects of hormone replacement therapy on ambulatory blood pressure and vascular
responses in normotensive women.
AB - The effects of chronic oestrogen replacement therapy (ERT) (conjugated equine
oestrogen 0.625 mg/day) and combined oestrogen and progestogen replacement
therapy (HRT) (ERT plus continuous medroxyprogesterone acetate 5 mg/day) on 24-h
ambulatory blood pressure recordings, forearm vascular resistance (FVR) and FVR
responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were
studied in 17 normotensive postmenopausal women in a 3-month randomized, double
blind, placebo-controlled crossover trial with 1 month of therapy in each
treatment arm. During the last few days of each 1-month treatment period, the
subjects underwent 24-h ambulatory blood pressure recordings and measurements of
FVR responses. ERT and HRT reduced mean 24-h diastolic blood pressure by 4 and 5
mmHg, systolic blood pressure by 6 and 9 mmHg and mean 24-h heart rate by 5 and 3
beats/min, respectively for ERT and HRT (p < 0.05). Basal FVR was reduced by
approximately 18% by ERT and HRT, but FVR responses to noradrenaline, angiotensin
II, acetylcholine and nitroprusside were unaffected. ERT and HRT therapy for 1
month lowers blood pressure and basal FVR, but does not appear to influence FVR
responses to acetylcholine, nitroprusside, noradrenaline and angiotensin II.
PMID- 28425784
TI - Vascular Endothelial Cell Activation Associated with Increased Plasma Asymmetric
Dimethyl Arginine in Children and Young Adults with Hypertension: A Basis for
Atheroma?
AB - The mechanism behind the development of vascular complications of hypertension in
the young human remains unclear. To explore the role of vascular endothelium
generated nitric oxide (a known mediator of leucocyte-platelet-endothelial
interactions) in this context, we investigated markers of endothelial activation
(soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion
molecule-1 (ICAM-1), P-selectin, E-selectin), and von Willebrand factor and the
plasma level of the endogenous nitric oxide inhibitor asymmetric dimethyl
arginine (ADMA) in a group of 31 (17 male, mean age 9.4 years) hypertensive and 9
(4 male, mean age 9.1 years) healthy, normotensive children and young adults. We
found raised levels of ADMA (mean (SEM) 235 (32) n mol/l) and VCAM-1 (median
(range) 1237 (675-2700) ng/ml) in the plasma of hypertensive subjects compared
with those of normotensives (ADMA, 103 (7) n mol/l and VCAM-1, 1005 (425-1650)
ng/ml, respectively). Furthermore, in hypertensive subjects, higher VCAM-1
concentrations (r = 0.66, p < 0.001) and vWF concentrations (r = 0.37, p = 0.04)
were significantly associated with a higher plasma ADMA level. Therefore, an
isolated increase in plasma VCAM-1 in hypertensives in association with raised
ADMA may signify a selective ?non-inflammatory? endothelial activation triggered
by endothelial nitric oxide synthase inhibition. Since VCAM-1 is implicated in
the origins of atherosclerosis, ADMA may be an important contributory factor in
increasing the risk of atheroma formation in hypertensive children and young
adults.
PMID- 28425785
TI - Lack of Association of Angiotensin-converting Enzyme and Angiotensinogen Genes
Polymorphisms with Left Ventricular Structure in Young Normotensive Men.
PMID- 28425786
TI - Organ damage in treated middle-aged hypertensives compared to normotensives:
results from a cross-sectional study in general practice.
AB - BACKGROUND: High blood pressure contributes to organ damage. However, during the
past two decades there have been great advances in the medical treatment of
hypertension. Technical progress has also made it easier to visualize organ
damage. Hence we found it of interest to examine heart, brain and retina in a
group of middle-aged treated hypertensives, comparing the results with those from
a group of middle-aged normotensives. METHODS: The subjects were 40 (20 men)
treated hypertensives and 40 (20 men) normotensives, who had previously taken
part in a study in which ambulatory blood pressure monitoring had been performed.
The heart was examined by echocardiography, the retina by photography and the
brain by magnetic resonance imaging. RESULTS: Office blood pressure and 24-h
systolic/diastolic blood pressure (S/D) were 141/86 (13/7) mmHg and 128/81 (11/6)
mmHg in the hypertensives and 125/78 -(10/8) mmHg and 118/74 (8/5) mmHg in the
normotensives, respectively. Left ventricular mass was 101 (27) g/m2 in the
hypertensives and 85 (18) g/m2 in the normotensives (p = 0.0025). The
corresponding figures for the left atrium were 21.1 (3.1) mm/m2 in the
hypertensives and 19.5 (2.2) mm/m2 in the normotensives (p < 0.001). E/A wave
quotient was 1.09 (0.26) in the hypertensives and 1.26 (0.26) in the
normotensives (p = 0.0045), while left ventricular systolic function did not
differ between the groups. Ten hypertensives and one normotensive subject had
left ventricular mass above normal range. Narrow retinal arteries were found in
22 hypertensives and 8 normotensives (p < 0.001). Brain magnetic resonance
changes (deep white matter and/or periventricular) were found in 19 hypertensives
and 9 normotensives (p = 0.0431). CONCLUSIONS: The hypertensives differed
significantly from the normotensives concerning left ventricular mass, left
atrium, left ventricular diastolic function and retinal vessel changes. Deep
white matter and periventricular changes in the brain were also significantly
different in the two groups. We can only speculate as to whether earlier
antihypertensive treatment or further blood pressure reduction could have
affected these differences.
PMID- 28425787
TI - Defining the proteomic landscape of rheumatoid arthritis: progress and
prospective clinical applications.
AB - INTRODUCTION: The heterogeneity of Rheumatoid Arthritis (RA) and the absence of
clinical tests accurate enough to identify the early stages of this disease have
hampered its management. Therefore, proteomics research is increasingly focused
on the discovery of novel biological markers, which would not only be able make
an early diagnosis, but also to gain insight into the different pathological
mechanisms underlying the heterogeneity of RA and also to stratify patients,
which is critical to enabling effective treatments. Areas covered: The proteomic
approaches that have been utilised to provide knowledge about RA pathogenesis,
and to identify biomarkers for RA diagnosis, prognosis, disease monitoring and
prediction of response to therapy, are summarized. Expert commentary: Although
each proteomic study is unique in its design, all of them have contributed to the
understanding of RA pathogenesis and the discovery of promising biomarkers for
patient stratification, which would improve clinical care of RA patients. Still,
efforts need to be made to validate these findings and translate them into
clinical practice.
PMID- 28425788
TI - The Outcome of STOP-Hypertension-2 in Relation to the 1999 WHO/ISH Hypertension
Guidelines.
AB - The 1999 hypertension management guidelines issued by the World Health
Organization and the International Society of Hypertension emphasize the
importance of blood pressure reduction in the prevention of cardiovascular
events. Furthermore, they conclude that the benefits of treatment are due to
blood pressure lowering per se, rather than to any specific antihypertensive
therapy. The results of the second Swedish Trial in Old Patients with
Hypertension (STOP-Hypertension-2) are consistent with these recommendations,
since in this trial angiotensin converting enzyme (ACE) inhibitors and calcium
antagonists reduced blood pressure to the same extent as conventional therapy
with beta-blockers and diuretics in elderly hypertensive patients, and the three
treatments produced similar reductions in the risk of cardiovascular events.
Furthermore, a first subgroup analysis of cardiovascular mortality showed that
the three treatments seemed equally effective in diabetic patients. The STOP
Hypertension-2 data, therefore, are fully consistent with the 1999 hypertension
management guidelines, and underline the advantages offered by both older and
newer antihypertensive therapies.
PMID- 28425789
TI - The Problem of Hypertension in the Elderly.
AB - Since most developed countries have an ageing population, the prevalence of
hypertension is increasing. This age-driven increase in cardiovascular risk is an
important factor contributing to the increasing burden of mortality and morbidity
associated with cardiovascular disease. Today, there is a strong rationale for an
aggressive approach to hypertension since antihypertensive treatment has been
shown to reduce cardiovascular mortality and morbidity in the elderly. It is
likely that increasing emphasis will be placed on control of isolated and
borderline systolic hypertension, which are the predominant forms of hypertension
in elderly patients. The recent second Swedish Trial in Old Patients with
Hypertension (STOP-Hypertension-2) represents an important contribution to the
literature since it shows that newer antihypertensive agents, such as angiotensin
converting enzyme (ACE) inhibitors and calcium antagonists, are as effective as
older agents in reducing cardiovascular mortality and morbidity in elderly
patients.
PMID- 28425790
TI - Results of the STOP-Hypertension-2 Trial.
AB - The second Swedish Trial in Old patients with Hypertension (STOP-Hypertension-2)
was conducted to compare the effects of 'newer( antihypertensive therapies
(angiotensin converting enzyme [ACE] inhibitors and calcium antagonists) and
established therapies (beta-blockers and diuretics) on cardiovascular mortality
and morbidity in elderly hypertensive patients. A total of 6614 patients were
randomized to receive conventional treatment, ACE inhibitors or calcium
antagonists, and followed for a mean of 5 years. The primary endpoint was a
combination of fatal stroke, fatal myocardial infarction and other fatal
cardiovascular disease; secondary endpoints were a combination of fatal or non
fatal stroke or myocardial infarction, and other cardiovascular mortality. The
three treatments produced similar reductions in supine systolic blood pressure.
There were no significant differences in the risk of cardiovascular events
between patients receiving conventional therapy and those receiving newer
therapies. All three treatments were well tolerated. The STOP-Hypertension-2
results thus add to the extensive literature showing the benefits of blood
pressure reduction in elderly hypertensive patients. Moreover, they are
consistent with current management guidelines which emphasise the importance of
the achieved blood pressure reduction in the prevention of cardiovascular events.
PMID- 28425791
TI - Target Blood Pressure in Elderly Hypertensive Patients: How Low Should You Go?
AB - Epidemiological studies have highlighted the increasing prevalence of
hypertension with age, and the associated increase in the risk of cardiovascular
disease. A number of randomized controlled trials have shown that
antihypertensive treatment significantly reduces cardiovascular mortality and
morbidity in elderly patients, and there is evidence that the benefit achieved is
related to the extent to which blood pressure is lowered. Furthermore, a recent
analysis of data from the Hypertension Optimal Treatment (HOT) Study shows that
intensive therapy produces significantly greater reductions in blood pressure in
elderly patients than in younger patients, without increasing the risk of adverse
events. As a result, the latest management guidelines recommend that the goal of
antihypertensive therapy in elderly patients should be to achieve at least high
normal blood pressures (below 140/90 mmHg). Angiotensin II type 1 receptor
antagonists offer a new option for antihypertensive therapy in elderly patients,
and trials such as the Study on Cognition and Prognosis in the Elderly (SCOPE)
are currently investigating the effect of these agents on cardiovascular
mortality and morbidity in elderly hypertensive patients.
PMID- 28425792
TI - The Role of Ambulatory Blood Pressure Monitoring in Elderly Hypertensive
Patients.
AB - There is strong evidence that ambulatory blood pressure measurements show only
limited agreement with blood pressures measured in the clinic ('office( blood
pressures), and are more relevant to the prognosis of hypertension. Several
markers of end-organ damage, for example, have been shown to correlate more
strongly with 24-h blood pressure than with office blood pressure. In addition,
end-organ damage has been shown to be correlated with 24-h blood pressure
variability. Ambulatory blood pressure monitoring (ABPM) has revealed a number of
differences between the blood pressure profiles of elderly and younger patients.
Since 24-h blood pressure control is now widely accepted as an important goal of
antihypertensive therapy, ABPM has a potentially useful role in monitoring
treatment in clinical trials in elderly patients.
PMID- 28425793
TI - Is it Possible to Differentiate between Angiotensin II Type 1 (AT1) Receptor
Blockers in Normotensive Volunteers?
AB - Variability of blood pressure responses to inhibition of the renin-angiotensin
system is influenced by factors inherent in the patient, such as renin status,
and by drug-specific factors, such as pharmacokinetics. The pharmacokinetic
pharmacodynamic interactions of two doses of candesartan cilexetil, which is an
ester prodrug of the insurmountable angiotensin II type 1 (AT 1 ) receptor
blocker candesartan, were compared with those of the standard dose of losartan in
normotensive volunteers whose renin status was controlled by mild sodium
depletion. In a double-blind, placebo-controlled crossover study, the effects of
single oral doses of candesartan cilexetil, 8 mg and 16 mg, and losartan, 50 mg,
were compared for 24 h in 16 healthy individuals pretreated with a single 40-mg
dose of furosemide. Mean blood pressure was recorded by repeated measurements
using the oscillometric method. In addition, measurements were made of plasma
active renin, angiotensin I and angiotensin II, and plasma levels of candesartan
and EXP-3174, the active metabolites of candesartan cilexetil and losartan,
respectively, were determined by high-performance liquid chromatography and
correlated to pharmacodynamic changes. The large interindividual variability of
EXP-3174 levels in subjects who received losartan revealed a significant
correlation between active renin and peak drug levels ( r = 0.77, n = 16, p <
0.01). Such a correlation was not found within either group of individuals who
received candesartan cilexetil, because of lower interindividual pharmacokinetic
variability. A dose-response relationship was found between plasma renin and
candesartan when both doses of candesartan cilexetil were analysed. The
pharmacodynamic effects of a single oral dose of candesartan cilexetil, 16 mg,
were superior to those of candesartan cilexetil, 8 mg, and losartan, 50 mg (see
Table). This conclusion has been confirmed by the results of a parallel-group,
dose-determination study performed in hypertensive patients. The less variable
pharmacokinetic-pharmacodynamic interaction for candesartan cilexetil than for
losartan could account for the smooth 24-h reduction in blood-pressure found in
patients treated with candesartan cilexetil. These results suggest not only that
AT 1 -receptor antagonists can be differentiated, but that they will not be
equally useful in clinical practice where, in contrast to clinical research,
clear evidence is more difficult to obtain because of variability in renin
status.
PMID- 28425794
TI - Differences Among Angiotensin II Type 1 Receptor Blockers: Characteristics of
Candesartan Cilexetil.
AB - Several angiotensin II type 1 (AT 1 ) receptor blockers are now available for the
treatment of hypertension. Although the agents in this class all act by blocking
the AT 1 -receptor, they differ in their pharmacokinetics and binding
characteristics. One of the newest AT 1 -receptor blockers, candesartan
cilexetil, is administered in an inactive form and is rapidly and completely
converted to the active drug, candesartan, during gastrointestinal absorption. In
vitro studies have shown that candesartan has the highest receptor affinity of
all the available AT 1 -receptor blockers and is not displaced from the receptor
by high concentrations of angiotensin II. The tight and long-lasting binding of
candesartan to the AT 1 -receptor provides effective blockade of the negative
cardiovascular effects of angiotensin II.
PMID- 28425795
TI - Angiotensin II Type 1 Receptor Blockade: a Novel Therapeutic Concept.
AB - Angiotensin II type 1 (AT 1 ) receptor blockers, such as candesartan, are
attractive alternatives to ACE inhibitors in the treatment of hypertension and
cardiovascular disease. Although angiotensin-converting enzyme (ACE) inhibitors
are able to suppress the renin-angiotensin system (RAS), their mechanism of
action may limit their clinical utility in the treatment of hypertension. For
example, they act as competitive inhibitors of ACE. This means that their effects
can be overcome by high levels of angiotensin I, which occur after ACE inhibition
due to removal of the negative feedback effect of angiotensin II on renal renin
release. ACE inhibitors are also unable to block the production of angiotensin II
by non-ACE-mediated pathways. Furthermore, ACE is not a specific enzyme. Its
inhibition therefore has effects on other substances, such as bradykinin, leading
to the class-specific side effects associated with ACE inhibitors. Candesartan,
on the other hand, binds insurmountably to the AT 1 -receptor, thereby providing
more complete blockade of the negative cardiovascular effects of angiotensin II
than is possible with ACE inhibitors. The specificity of AT 1 -receptor blockade
also ensures that efficacy is achieved without inducing the side effect of cough
that results from the non-specific consequences of ACE inhibition. Preclinical
and early clinical studies demonstrate that AT 1 -receptor blockers produce at
least the same degree of target-organ protection as has been demonstrated for ACE
inhibitors. Additional benefits of AT 1 -receptor blockers may arise from the
fact that, unlike ACE inhibitors, they do not prevent the activity of angiotensin
II on AT 2 -receptors in the heart, which is thought to reduce cardiac
remodelling. From a mechanistic perspective, therefore, AT 1 -receptor blockers
appear to have advantages over ACE inhibitors, in terms of a more complete
blockade of angiotensin II effects, while also avoiding the specific side effects
associated with ACE inhibition.
PMID- 28425796
TI - Achieving Quality 24-h Blood Pressure Control with Candesartan Cilexetil.
AB - Epidemiological evidence suggests that optimal blood pressure control requires
strategies that lower blood pressure consistently and fully throughout 24 h. In
order to maximize compliance, antihypertensive agents also need to be well
tolerated and effective when administered at a convenient once-daily dose. The
new angiotensin II type 1 (AT 1 ) receptor blocker candesartan binds tightly to,
and dissociates slowly from, the AT1-receptor and thereby provides long-lasting
suppression of the renin-angiotensin system. This is likely to explain its
pronounced antihypertensive efficacy, which is maintained smoothly over 24 h. The
trough-to-peak ratio is a useful measure of the persistence of antihypertensive
efficacy at the end of the dosing interval. This ratio was found to be close to
the ideal of 1.0 for candesartan cilexetil, -8 and 16 mg, whereas it was 0.7 for
the prototype AT 1 -receptor blocker losartan, 50 mg. The antihypertensive effect
of candesartan cilexetil, 16 mg, was also significantly greater than that of
losartan, 100 mg, as demonstrated by ambulatory blood pressure measurements 0-36
h after dosing and by clinic measurements 48 h after dosing. By controlling blood
pressure well beyond the normal dosing interval, candesartan cilexetil provides
cardiovascular protection even in those patients who may occasionally miss doses.
PMID- 28425797
TI - Candesartan Cilexetil, 16 mg, Provides a Greater Antihypertensive Effect than
Losartan, 50 mg, in Patients with Mild to Moderate Hypertension.
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker, which binds
tightly to and dissociates slowly from the AT 1 -receptor. These binding
characteristics underpin the long duration of action and antihypertensive
efficacy of candesartan, and help to differentiate it from losartan, which was
the first AT 1 -receptor blocker to be approved for the treatment of
hypertension. This study compared the antihypertensive effect and tolerability of
candesartan cilexetil, 8 or 16 mg once daily, with that of placebo and of
losartan, 50 mg once daily, in patients with mild to moderate primary
hypertension. The dose of 50 mg for losartan was chosen, as this is the dose
usually recommended; higher doses do not seem to result in further reductions in
blood pressure. Men and women, aged 20-80 years, with primary hypertension and a
sitting diastolic blood pressure (DBP) of 95-114 mmHg at the end of a 4-week
placebo run-in period, were randomized to once-daily, double-blind treatment with
candesartan cilexetil, 8 mg ( n = 82), candesartan cilexetil, 16 mg ( n = 86),
losartan, 50 mg ( n = 84), or placebo ( n = 85) for 8 weeks. Blood pressure was
measured 6 and 24 h after dosing, i.e. at the times of peak and trough effects,
respectively. Differences among treatments in changes in blood pressure from
randomization to the end of the study were assessed by analysis of variance.
Patients were defined as having responded to treatment if sitting DBP was 90 mmHg
or below at week 8 or if sitting DBP had been reduced by more than 10 mmHg from
baseline to week 8. The proportion of responders in each treatment group was 15%
for placebo, 46% for losartan, 50 mg, 50% for candesartan cilexetil, 8 mg, and
57% for candesartan cilexetil, 16 mg. The reduction in sitting DBP at trough (the
primary effect variable) was significantly greater in patients treated with
candesartan cilexetil, 16 mg, than in patients treated with losartan, 50 mg (see
Table). In addition, both doses of candesartan cilexetil had a trough-to-peak
ratio of approximately 1.0, compared with 0.7 for losartan. Both candesartan
cilexetil and losartan were well tolerated, with the incidence of adverse events
similar to placebo in both treatment groups. Overall, the most common new-onset
adverse events reported were headache and respiratory infection, both of which
are common in this type of patient population. In conclusion, candesartan
cilexetil, 8 or 16 mg once daily, is an effective and well-tolerated
antihypertensive treatment, with a trough-to-peak ratio close to 1.0. Candesartan
cilexetil, 16 mg once daily, produces a significantly greater reduction in blood
pressure than losartan, 50 mg once daily.
PMID- 28425798
TI - Improving Antihypertensive Efficacy while Maintaining Placebo-like Tolerability.
AB - Potency and efficacy, duration of action, organ-specific effects and tolerability
are the main considerations when choosing among antihypertensive therapies.
Candesartan has been shown in in vitro animal models to bind insurmountably to
the angiotensin II type 1 (AT 1 ) receptor, thus providing effective blockade of
all the major negative cardiovascular effects of angiotensin II. Its binding
characteristics differentiate candesartan from other AT 1 -receptor blockers.
Candesartan cilexetil has been found to produce a predictable and pronounced dose
dependent decrease in blood pressure, with placebo-like tolerability even at the
highest doses studied. In comparison with the standard 50-mg dose of losartan,
candesartan cilexetil, 16 mg, was significantly more effective in suppressing the
renin-angiotensin system and in reducing trough diastolic blood pressure. Pooled
results from placebo-controlled trials also indicate that candesartan cilexetil
has equivalent efficacy to irbesartan. In addition, the extent of blood pressure
lowering by candesartan cilexetil has been shown to be similar to that of agents
in the other major classes of antihypertensive drugs, and to be effective in
combination therapy with diuretics and calcium channel blockers. Candesartan
cilexetil combines 24-h blood pressure lowering with placebo-like tolerability
and is therefore an important advance in antihypertensive therapy.
PMID- 28425799
TI - Candesartan Cilexetil, a Novel Angiotensin II Antagonist, Provides Dose-dependent
Antihypertensive Effect with Maintained Tolerability.
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker that binds
tightly to and dissociates slowly from the AT 1 -receptor. It is administered as
a prodrug, candesartan cilexetil, which is completely converted to the active
compound, candesartan, during absorption in the gastrointestinal tract. Placebo
controlled studies have shown that candesartan cilexetil is an effective
antihypertensive drug. The individual studies, however, lacked the statistical
power to assess the dose-response relationship with high precision. A more
precise estimate of the effect of different doses may be achieved by pooling
similar studies in a meta-analysis. The primary objective of this meta-analysis
was to determine the dose-response relationship for the antihypertensive effect
of candesartan cilexetil. Six European randomized, double-blind, placebo
controlled, dose-response studies with candesartan cilexetil were reported by 30
September 1996. These studies enrolled similar patients (primary hypertension
with a sitting diastolic blood pressure [DBP] of 95-114 mmHg after a placebo run
in period) and had a similar design (parallel groups and fixed doses). The doses
investigated ranged from 2 to 16 mg once daily. All doses were not given in every
study, but all studies investigated at least two different doses of candesartan
cilexetil. The duration of the double-blind phase varied between studies, but was
at least 4 weeks (range: 4-12 weeks). The variable of primary interest was
sitting DBP measured 24 h after dose (trough effect). Each dose of candesartan
was analysed separately, and compared with placebo data only from those studies
in which that dose was given. The analysis was performed using an analysis of
covariance model. Placebo-corrected estimated mean blood pressure reductions from
baseline (randomization) to the end of the study and the 95% confidence intervals
for the true mean reductions were calculated for each dose. In total, 1498
hypertensive patients were randomized, of whom 1482 provided efficacy data and
were included in the analysis. The vast majority of patients (99%) were of
Caucasian origin. The placebo-corrected reductions in sitting DBP and sitting
systolic blood pressure (SBP) achieved with the different doses of candesartan
cilexetil are shown in the Table. Reductions in blood pressure were dose-related,
and age or gender did not influence the antihypertensive effect of candesartan
cilexetil. Furthermore, blood pressure reductions achieved in the standing
position were similar to those in the sitting position, i.e. there was no
indication of an abnormal orthostatic response during treatment with candesartan
cilexetil. Heart rate was not significantly influenced by candesartan cilexetil.
Adverse events occurred in a similar proportion of patients treated with placebo
or candesartan cilexetil and did not increase with the dose. Candesartan
cilexetil was equally well tolerated in young and elderly patients and in men and
women. Thus, in European patients with mild to moderate hypertension, candesartan
cilexetil provides a clinically significant, dose-dependent, antihypertensive
effect in doses ranging from 4 to 16 mg once daily. The optimal maintenance doses
of candesartan cilexetil appear to be 8 or 16 mg once daily in most patients.
PMID- 28425800
TI - Candesartan Cilexetil is not Associated with Cough in Patients with Enalapril
induced Cough.
AB - Treatment with angiotensin-converting enzyme (ACE) inhibitors is frequently
associated with persistent dry cough. This side effect is thought to be due to
the non-specific action of ACE inhibitors, which, in addition to suppressing the
renin-angiotensin system (RAS), leads to the accumulation of kinins, encephalins
and other biologically active peptides. Candesartan cilexetil is a new, long
acting angiotensin II type 1 (AT 1 ) receptor blocker, which offers a more
specific means of suppressing the RAS than can be achieved with ACE inhibitors.
In this study, we compared the incidence and severity of cough during treatment
with candesartan cilexetil, enalapril and placebo in patients with hypertension
and enalapril-induced cough. Men and women, aged 20-80 years, with a history of
medically treated primary hypertension and ACE-inhibitor-related cough were
enrolled. The presence of cough was confirmed during a 4-week challenge period
with enalapril, 10 mg, which abated during a subsequent 4-week washout period
with placebo. Patients with confirmed ACE-inhibitor-related cough were then
randomized to double-blind treatment with candesartan cilexetil, 8 mg once daily
( n = 62), enalapril, 10 mg once daily ( n = 66), or placebo ( n = 26). Baseline
blood pressure was similar in all groups. Although blood pressure was recorded
during the study, this was for safety monitoring, and the measurements were not
standardized in relation to study drug intake or time of day. The frequency of
dry cough was recorded on a visual analogue scale (VAS). For each assessment,
patients marked a cross on a straight horizontal 100 mm line, rating cough
frequency from 'none of the time( at one end of the line to 'all of the time( at
the other end. The impact of treatment on quality of life was also studied, using
the Symptom Assessment (SA) questionnaire and the Minor Symptom Evaluation (MSE)
profile. The SA questionnaire assessed the severity of nine symptoms, including
dry cough, by means of a five-graded Likert scale (not at all, a little,
moderately, quite a bit, extremely). Changes in the three dimensions of the MSE
profile - contentment, vitality and sleep - were recorded using a VAS.
Candesartan cilexetil was superior to enalapril regarding the change in frequency
( p = 0.001) and severity ( p < 0.001) of dry cough. After 8 weeks of treatment,
the proportions of patients with cough were 26.9% for placebo, 35.5% for
candesartan cilexetil and 68.2% for enalapril ( p < 0.001, candesartan cilexetil
versus enalapril; p > 0.20, candesartan cilexetil versus placebo). Treatment with
candesartan cilexetil did not compromise patients' well-being. Compared with
placebo, candesartan cilexetil was superior in terms of its effect on
contentment; similar trends were noted for vitality and sleep, although the
differences were not significant. When all adverse events were considered,
candesartan cilexetil was very well tolerated. No serious adverse events occurred
in the candesartan cilexetil or placebo groups, while three patients in the
enalapril group reported serious adverse events (chest pain, agranulocytosis,
accidental fracture). No treatment-related changes of clinical relevance could be
found with regard to laboratory variables, ECG or vital signs/physical findings,
except the anticipated blood pressure reduction in the active treatment groups.
In conclusion, candesartan cilexetil is not associated with cough in hypertensive
patients with previous ACE-inhibitor-induced cough. The incidence of dry cough in
patients treated with candesartan cilexetil was similar to that of placebo and
lower than that of enalapril.
PMID- 28425801
TI - Efficacy and Tolerability of Candesartan Cilexetil in Special Patient Groups.
AB - Patients with hypertension do not comprise a homogeneous group, and the majority
present with a variety of concomitant and associated conditions. Antihypertensive
therapies should therefore be effective and well tolerated in a wide range of
patients and should, ideally, ameliorate the negative target-organ effects of
hypertension, such as atherosclerosis, cardiovascular remodelling and renal
impairment. Evidence is accumulating that the new angiotensin II type 1 receptor
blocker, candesartan cilexetil, lowers blood pressure effectively and is well
tolerated in a variety of patient groups, including women and the elderly. In
patients with severe hypertension, a treatment schedule based on candesartan
cilexetil, with the addition of diuretic and calcium antagonist therapy as
needed, has been found to control blood pressure successfully. Candesartan
cilexetil does not affect glucose tolerance or lipid profiles in patients with
diabetes mellitus, and it is not associated with any of the side effects of other
antihypertensive agents that would make it unsuitable for use in patients with
pulmonary disease. Initial clinical studies have indicated that candesartan
cilexetil is well tolerated and effective in patients with heart failure.
Furthermore, the available evidence shows that treatment with candesartan
cilexetil can reverse the negative effects of hypertension on left ventricular
hypertrophy and microalbuminuria. It therefore appears that the pronounced
efficacy and placebo-like tolerability of candesartan cilexetil, as demonstrated
in large clinical trials of patients with mild to moderate hypertension, can be
extended to a wide range of specific patient groups.
PMID- 28425802
TI - Candesartan Cilexetil, a Novel Angiotensin II Type 1 (AT1) Receptor Blocker,
Reduces Microalbuminuria in Patients with Type II Diabetes Mellitus and Mild
Hypertension.
AB - Microalbuminuria is a predictor of nephropathy in patients with type I or type II
diabetes mellitus, and interventions that decrease albuminuria are likely to
postpone the development of severe renal impairment. Suppression of the renin
angiotensin system by angiotensin-converting enzyme (ACE) inhibition has been
effective in this respect. However, direct inhibition of the negative
cardiovascular effects of angiotensin II by means of an angiotensin II type 1 (AT
1 ) receptor blocker would be expected to produce reductions in albuminuria
similar to those produced by ACE inhibition. In this study, we assessed the
effect of candesartan cilexetil on microalbuminuria in patients with type II
diabetes mellitus and mild hypertension. The analysis was performed in a subset
of patients ( n = 35) with microalbuminuria (10-100 mg in an overnight urine
sample) at randomization in a large double-blind, placebo-controlled study. The
subset was part of a study investigating the effect of candesartan cilexetil on
blood glucose homeostasis and the blood lipid profile in patients with stable
type II diabetes mellitus, mild hypertension (diastolic blood pressure 90-100
mmHg) and serum creatinine levels below 150 7 mol/l for men and below 120
w mol/l for women. Patients were randomized, after a 4-week placebo run-in
period, to 12 weeks of double-blind treatment with candesartan cilexetil, 8-16 mg
( n = 83), or placebo ( n = 78) once daily. After 12 weeks of treatment,
candesartan cilexetil did not influence blood glucose homeostasis or the blood
lipid profile compared with placebo. Body weight remained unchanged in both
treatment groups. Median urinary albumin excretion decreased by 57%, from 28.5 to
12.2 mg/12 h, in patients treated with candesartan cilexetil ( n = 15), whereas
it increased by 9%, from 30.2 to 32.8 mg/12 h, in the placebo group ( n = 20; p =
0.03 for the difference between treatments). The mean reduction in diastolic
blood pressure was 6.4 mmHg in the group given candesartan cilexetil and 3.6 mmHg
in the group given placebo. In conclusion, 12 weeks of treatment with the AT 1
receptor antagonist candesartan cilexetil reduced microalbuminuria in patients
with stable type II diabetes mellitus and mild hypertension. Thus, candesartan
cilexetil appears to have the potential for renal protection in this patient
category.
PMID- 28425803
TI - Improving Prognosis in Hypertension: Exploring the Benefits of Angiotensin II
Type 1 Receptor Blockade.
AB - Prognosis can be improved in hypertensive patients not only by reducing blood
pressure, but probably also by effective suppression of adverse neurohormonal
influences. Inhibition of the renin-angiotensin system by angiotensin-converting
enzyme inhibitors effectively reduces left ventricular hypertrophy and decreases
morbidity and mortality due to heart failure, as well as slowing the progression
of renal disease. Initial data from studies of angiotensin II type 1 (AT 1 )
receptor blockers indicate that these agents should also be effective in reducing
cardiac and renal damage. In this class, candesartan, by virtue of its tight and
long-lasting binding to the AT 1 -receptor, provides pronounced 24-h blood
pressure control with effective blockade of all the major negative cardiovascular
effects of angiotensin II. Candesartan cilexetil has also been shown to be
effective and well tolerated in combination with hydrochlorothiazide in those
hypertensive patients who require more than one agent to reach their target blood
pressure.
PMID- 28425804
TI - Reducing Cardiovascular Morbidity and Mortality in the Elderly.
AB - Candesartan cilexetil is highly effective at lowering blood pressure, whilst
maintaining placebo-like tolerability, in a wide range of patient groups.
Although the benefit of lowering blood pressure in elderly patients with moderate
hypertension has been demonstrated in several large-scale clinical trials,
elderly patients with mild hypertension have rarely been studied. The high
incidence of cardiovascular and cerebrovascular mortality and morbidity,
including dementia, in the elderly means that control of blood pressure is
particularly important in this patient group. A major new international clinical
trial - SCOPE (Study on COgnition and Prognosis in the Elderly) - has therefore
been initiated. This is a prospective, randomized, double-blind, parallel
comparison of the effects of candesartan cilexetil, 8 or 16 mg once daily, and
placebo in about 5000 patients who will be followed for a mean of 2.5 years.
SCOPE is the first study designed to assess the effect of antihypertensive
therapy in elderly patients (70-89 years of age) with mild hypertension (sitting
systolic blood pressure of 160-179 mmHg and/or sitting diastolic blood pressure
of 90-99 mmHg). The primary objective of the study is to determine the effect of
candesartan cilexetil on major cardiovascular events (cardiovascular death, non
fatal stroke and myocardial infarction, and silent myocardial infarction), while
an important secondary objective is to determine the effect of such treatment on
the prevention of cognitive impairment. SCOPE should provide definitive evidence
of the cardiovascular and cerebrovascular benefits of treating mildly
hypertensive elderly patients with angiotensin II type 1 receptor blockers, which
not only reduce blood pressure, but may also provide significant protection from
the negative effects of angiotensin II on target organs.
PMID- 28425805
TI - Study on COgnition and Prognosis in the Elderly (SCOPE): Design and Objectives.
AB - Hypertension is a major risk factor for cardiovascular events, including stroke,
as well as for white matter lesions of the brain. There is also evidence to link
cognitive impairment and dementia to hypertension. However, it has not been
established whether antihypertensive treatment of elderly patients with a
diastolic blood pressure (DBP) in the range 90-99 mmHg provides protection
against major cardiovascular events and cognitive impairment. The Study on
COgnition and Prognosis in the Elderly (SCOPE) is the first study designed to
assess the effects of antihypertensive drug treatment on major cardiovascular
events and cognitive function in elderly patients with mild hypertension. SCOPE
is a prospective, randomized, double-blind, parallel comparison of the effects of
the angiotensin II type 1 (AT 1 ) receptor blocker candesartan cilexetil and
placebo on major cardiovascular events (myocardial infarction [MI], stroke and
cardiovascular death), cognitive function as measured by the Mini-Mental State
Examination (MMSE), quality of life (QoL) and health economics. The study has
included both men and women, aged 70-89 years of age, with systolic blood
pressure (SBP) of 160-179 mmHg and/or DBP of 90-99 mmHg and an MMSE score of 24
or above. Nearly 5000 patients have been recruited and will be followed for a
mean period of 2.5 years. After a run-in period of 1-3 months, patients were
randomized to receive placebo or candesartan cilexetil, 8 mg once daily, which
has been shown to provide effective and long-lasting blood pressure reductions,
while maintaining placebo-like tolerability, in elderly patients. All previous
antihypertensive treatment was standardized to hydrochlorothiazide (HCTZ), 12.5
mg, at enrolment. At any time during the study, the dose of study drug will be
doubled if SBP rises above 160 mmHg or DBP rises above 85 mmHg. If an SBP above
160 mmHg or a DBP above 90 mmHg is observed despite the increase in study
medication, additional antihypertensive medication with HCTZ is recommended.
Assessments to be made during the study will include blood pressure, heart rate,
ECG, MMSE, health economics and QoL. Data on adverse events and clinical events
will also be collected throughout the study. SCOPE is organized and co-ordinated
by an Executive Committee, a Steering Committee, an Independent Safety Committee,
an Independent Event Committee and a Co-ordinating Centre. Countries
participating in the Study include Belgium, Canada, Finland, France, Germany, UK,
Hungary, Israel, Norway, Poland, Portugal, Spain, Sweden, The Netherlands and the
USA. Inclusion of patients was completed in January 1999 and at that time 4964
patients were randomized. The baseline characteristics of these patients are
shown in the Table.
PMID- 28425806
TI - Preserving Target-organ Function with Candesartan Cilexetil in Patients with
Hypertension.
AB - Epidemiological evidence suggests that reducing blood pressure alone in
hypertensive patients delays the onset of cardiovascular events without
necessarily preventing the progression of chronic target-organ disease, such as
end-stage renal failure and heart failure. Successful clinical management of
hypertensive patients will therefore not be possible unless therapies are aimed
both at the effective control of blood pressure and at the preservation of target
organ function. The new angiotensin II type 1 (AT 1 ) receptor blocker
candesartan cilexetil has been shown to be effective in reducing target-organ
damage in animal models of hypertension, even at doses that do not produce
significant reductions in blood pressure. Protective effects of candesartan
cilexetil towards the heart and kidney have also been demonstrated in the
clinical studies that have been conducted to date. Thus, candesartan cilexetil
has been shown to induce regression of left ventricular hypertrophy within 8-12
weeks of treatment and to improve renal haemodynamics, both acutely and after 6
weeks of treatment in hypertensive patients. Furthermore, in hypertensive
patients with co-existent non-insulin-dependent diabetes mellitus and
microalbuminuria, 12 weeks of treatment with candesartan cilexetil, 8-16 mg,
significantly reduced urinary albumin excretion. Clinical evidence is therefore
accumulating that the antihypertensive efficacy and tolerability profile already
established for candesartan cilexetil is combined with the renal and
cardioprotective effects necessary for optimal management of hypertension.
PMID- 28425807
TI - Antihypertensive Effects and Tolerability of Candesartan Cilexetil in an Elderly
Population.
AB - The pharmacokinetics and pharmacodynamics of antihypertensive drugs are often
influenced by age, and may be different in elderly and younger patients. The
choice of drug and dosage in the elderly therefore merits special consideration.
The aim of this placebo-controlled study was to determine the efficacy and
tolerability of the angiotensin II type 1 (AT 1 ) receptor blocker candesartan
cilexetil with placebo in elderly patients with primary hypertension. Men and
women, aged 65 years or older and with supine diastolic blood pressure (DBP) of
95-114 mmHg, were randomized to double-blind, once-daily treatment with
candesartan cilexetil, 8 mg ( n = 96), or placebo ( n = 97) for 12 weeks. The
dose was increased to 16 mg once daily if DBP was greater than 90 mmHg after 6
weeks of treatment. Forty-nine per cent of the patients remained on the 8 mg
dose. At each visit, systolic blood pressure (SBP) and DBP were measured 24 h
after dosing. After the first dose following randomization, blood pressure was
also measured at 2 and 4 h. Placebo-corrected changes in supine blood pressure
with candesartan cilexetil are shown in the Table. At the end of the study, the
mean reductions in placebo-corrected supine DBP and SBP in patients receiving
candesartan cilexetil were 7.5 mmHg and 13.6 mmHg, respectively ( p < 0.001 vs
placebo). The incidence of adverse events in this treatment group was similar to
that in the placebo group. Only four patients in the candesartan cilexetil group
withdrew due to adverse events, compared with ten in the placebo group. There was
no evidence of an orthostatic effect. In conclusion, in elderly hypertensive
patients, candesartan cilexetil, 8-16 mg once daily, is an effective and well
tolerated antihypertensive treatment, which has a smooth onset of action and no
exaggerated response after the first dose.
PMID- 28425808
TI - The Renin-Angiotensin System and Cardiovascular Disease.
AB - Suppression of the renin-angiotensin system (RAS) with angiotensin-converting
enzyme (ACE) inhibitors is an established method for controlling blood pressure
and reducing the risk of cardiovascular disease. In addition to reducing blood
pressure, suppression of the RAS is able to protect against the target-organ
damage that results from hypertension. Unfortunately, despite the use of ACE
inhibitors and agents from the other classes of conventional antihypertensives,
effective control of blood pressure remains poor. A major contribution to this
failure to control blood pressure appears to be lack of compliance with the
prescribed medication, arising from the presence of unacceptable side effects.
Angiotensin II type 1 (AT 1 ) receptor blockers, such as candesartan, are the
latest class of antihypertensive agent to be developed. They target the AT 1
receptor - the final common pathway for all the known negative cardiovascular
effects of angiotensin II - and provide pronounced antihypertensive efficacy
without the side effects of cough and angioneurotic oedema that are associated
with the use of ACE inhibitors.
PMID- 28425809
TI - A Combination of Candesartan Cilexetil/hydrochlorothiazide (HCTZ), 8/12.5 mg, has
a Similar Antihypertensive Efficacy and is Better Tolerated than Lisinopril/HCTZ,
10/12.5 mg.
AB - Monotherapy with an antihypertensive agent is likely to achieve a desirable
lowering of blood pressure in about 50% of patients. The remaining proportion of
patients are likely to be only partially responsive or unresponsive, even if
appropriate dose adjustments are made. For these patients, combination therapy
usually leads to better control of hypertension. The aim of this study was to
compare the antihypertensive effect and tolerability of a once-daily combination
of the angiotensin II type 1 (AT 1 ) receptor blocker candesartan cilexetil, 8
mg, and the diuretic hydrochlorothiazide (HCTZ), 12.5 mg, with a combination of
the angiotensin-converting enzyme inhibitor, lisinopril, 10 mg, and HCTZ, 12.5
mg, in patients with primary hypertension. The study included men and women, 20
80 years of age, with sitting diastolic blood pressure (DBP) of 95-114 mm Hg.
After a run-in period of 2 weeks on any antihypertensive monotherapy, 355
patients were randomized to double-blind treatment with either a combination of
candesartan cilexetil/HCTZ, 8/12.5 mg, or a combination of lisinopril/HCTZ,
10/12.5 mg, for 26 weeks. Blood pressure was measured 24 h after dose intake, the
primary efficacy variable being the change in sitting DBP at trough between
baseline and 26 weeks of treatment. Reductions in mean sitting DBP after 26 weeks
were similar for both combination treatments. In addition, no differences were
found between the two treatment groups regarding standing DBP, sitting and
standing systolic blood pressure, heart rate, and the proportion of responders
and controlled patients. Significantly fewer patients reported at least one
adverse event with candesartan cilexetil/HCTZ than with lisinopril/HCTZ (68.9% vs
79.5%, p = 0.02; see Table). Furthermore, the proportion of patients
spontaneously reporting cough was markedly higher in the lisinopril/HCTZ group
(23.9%) than in the candesartan cilexetil/HCTZ group (5.0%). Thus, although the
combinations of candesartan cilexetil/HCTZ, 8/12.5 mg once daily, and
lisinopril/HCTZ, 10/12.5 mg once daily, had similar antihypertensive efficacy in
patients with mild to moderate hypertension during the 26-week treatment period,
candesartan cilexetil/HCTZ was significantly better tolerated than
lisinopril/HCTZ.
PMID- 28425810
TI - Candesartan, an Insurmountable Antagonist of Angiotensin II-mediated Contractile
Effects in Isolated Vascular Preparations: Comparison with Irbesartan, Losartan
and its Active Metabolite (EXP-3174).
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker that produces
more effective 24-h blood pressure lowering than losartan in hypertensive
patients. In in vitro tissue preparations, candesartan displays insurmountable
antagonism of the responses to angiotensin II. Both irbesartan and EXP-3174, the
active metabolite of losartan, have also previously been described in some
studies as insurmountable AT 1 -receptor blockers, whereas losartan exhibits
surmountable blockade of the AT 1 -receptor. We compared the properties of
candesartan, irbesartan, losartan and EXP-3174 in isolated vascular preparations
of rat portal vein and rabbit aortic strips. The concentrations of the different
AT 1 -receptor antagonists that were effective in these in vitro preparations
were also correlated to the non-protein bound plasma concentrations obtained in
clinical use. Preparations of the rabbit aorta and the rat portal vein were
dissected, mounted on a force-displacement transducer and submerged in oxygenated
Krebs' buffer at 37 degrees C. The vessel strips were pre-stretched to a passive
force of 5 and 20 mN for portal vein and aorta, respectively. The response to
angiotensin II, measured as the mean force development in response to increasing
concentrations of angiotensin II, was recorded in the absence and presence of
candesartan, 0.003-10 nmol/l, irbesartan, 1-100 nmol/l, losartan, 1-100 nmol/l,
and EXP-3174, 0.01-10 nmol/l, for a period of 90 min. In rabbit aortic strips,
candesartan caused a non-parallel shift and suppression of the angiotensin II
concentration-response curve, with complete suppression of the response to
angiotensin II at a dose of candesartan of 1 nmol/l. In contrast, irbesartan,
losartan and EXP-3174 all caused a parallel shift of the concentration-response
curve. No suppression of the angiotensin II response was seen with losartan,
while its active metabolite caused saturable suppression of the maximal response
at higher concentrations. For irbesartan, some degree of suppression of the
maximal response could not be excluded at the highest concentration studied.
Similar concentration-response curves were obtained in rat portal vein. Data on
protein binding for the different AT 1 -receptor blockers are variable in the
literature. Plasma protein binding for the different AT 1 -receptor blockers was
determined (in triplicate) by liquid chromatography with fluorescence detection
after equilibrium dialysis (6 h) of cold drug at a concentration of 1500 nmol/l.
Protein binding was high (see Table) and, for candesartan, losartan and its
active metabolite EXP-3174, in accordance with previously reported levels. For
irbesartan, a large discrepancy in protein binding between previously reported
and the present experimental data, obtained from two different non-associated
laboratories, was found. The higher plasma protein binding for irbesartan found
in the present study may explain why high doses of irbesartan seem to be needed
for clinical efficacy. It appears unlikely that losartan exerts any significant
inhibitory effect at therapeutic plasma levels, and the main AT 1 -blocking
effect observed after oral losartan is probably exerted by EXP-3174. It is
concluded that AT 1 -receptor blockers differ in their ability to inhibit
angiotensin II-mediated vascular contraction, and that the antagonistic
characteristics are similar in vessel preparations of different origins and with
different degrees of AT 1 -receptor reserve.
PMID- 28425811
TI - Candesartan Causes Long-lasting Antagonism of the Angiotensin II Receptor
mediated Contractile Effects in Isolated Vascular Preparations: a Comparison with
Irbesartan, Losartan and its Active Metabolite (EXP-3174).
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker. It displays
insurmountable antagonism of angiotensin II responses, binding tightly to and
dissociating slowly from the AT 1 -receptor. The purpose of this study was to
compare the duration of angiotensin II antagonism by the AT 1 -receptor blockers
candesartan, irbesartan, losartan and its active metabolite EXP-3174 in an
isolated tissue preparation. The contractile response to angiotensin II was
studied in the isolated portal vein of the rat, during incubation with AT1
receptor blockers and after an extensive washout period. The portal vein
preparation was pre-stretched to a passive force of 5 mN in an organ bath filled
with oxygenated Krebs' buffer at 37 degrees C. The contractile tension developed
by the vascular smooth muscles was monitored using a force-displacement
transducer. The contractile response to repeated administration of angiotensin II
was recorded before, during and following exposure (for 30-180 min) to
candesartan, 0.1-1 nmol/l, irbesartan, 1-50 nmol/l, losartan, 30-100 nmol/l, and
EXP-3174, 1-10 nmol/l. Drug exposure was followed by washing for up to 2 h.
Candesartan produced a long-lasting blockade of the vascular contractile response
to angiotensin II, as shown by maintenance of inhibition during the washout
period. This effect of candesartan was independent of drug concentration and
exposure time prior to washing. Irbesartan, losartan and EXP-3174 also blocked
the angiotensin II-mediated contraction. However, in contrast to candesartan, the
responses to angiotensin II rapidly returned towards baseline values during the
washout period. The relatively short-lasting blockade by irbesartan, losartan and
EXP-3174 was also independent of drug concentration and exposure time prior to
washout. It is concluded that the AT 1 -receptor blockers differ in their ability
to inhibit angiotensin II-mediated vascular contraction, with candesartan
producing longer-lasting blockade than irbesartan, losartan and EXP-3174. The
mechanism of the persistent inhibitory effect of candesartan is at present
unclear. Possible explanations include tight binding and slow dissociation from
the AT 1 -receptor, tissue accumulation resulting in 'local( dissociation and
reassociation to the AT 1 -receptor, and stimulation of internalization of the AT
1 -receptor.
PMID- 28425812
TI - Exploring New Treatment Strategies in Heart Failure.
AB - Heart failure remains a major and increasing cause of mortality and morbidity,
even when the best available treatments are used. One of its key causes is
neuroendocrine activation via the sympathetic nervous system and the renin
angiotensin system (RAS). Neuroendocrine blockers of the sympathetic nervous
system (beta-blockers) and of the RAS (angiotensin-converting enzyme [ACE]
inhibitors and angiotensin II type 1 [AT 1 ] receptor blockers) therefore have an
important potential therapeutic role in heart failure. The promising results from
clinical trials with beta-blockers suggest that these drugs will become an
established part of the future management of patients with mild to moderate
symptomatic heart failure. Blockade of the RAS with ACE inhibitors has also been
shown to be effective in reducing the risk of morbidity and mortality in patients
with heart failure. Blockade of the AT1-receptor, with agents such as
candesartan, produces more specific and, theoretically, more complete blockade of
the major negative cardiovascular effects of angiotensin II than is possible
using ACE inhibitors, whilst maintaining placebo-like tolerability. Furthermore,
AT 1 -receptor blockade leads to increased stimulation of the angiotensin II type
2 (AT 2 ) receptor, which, according to experimental data, may have favourable
cardiovascular effects. Following encouraging results from two pilot studies, a
major new international study programme - CHARM (Candesartan in Heart failure -
Assessment of Reduction in Mortality and morbidity) - has been initiated to
define the clinical benefits of candesartan cilexetil in a wide variety of
patients with symptomatic heart failure. CHARM is the first study to accept all
relevant heart failure patients who may benefit from RAS blockade, irrespective
of their left ventricular function or tolerance of ACE inhibitors. The 6500
patients to be recruited will be divided among three integrated outcome studies.
Two of these studies will examine the effect of candesartan cilexetil versus
placebo in patients with an ejection fraction of 40% or less who are tolerant or
intolerant of ACE inhibitors. The third study arm will examine the benefits of
candesartan cilexetil in a previously seldom studied group: those with
symptomatic heart failure, but with preserved left-ventricular systolic function.
Recruitment of patients into the study has started.
PMID- 28425813
TI - Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity
(CHARM) Study Programme.
AB - Heart failure is a major cause of death, hospital admissions and poor quality of
life. It affects some 1-2% of the general population, increasing to up to 8% in
people over 75 years of age. Although treatment with angiotensin-converting
enzyme (ACE) inhibitors reduces symptoms and mortality, 50-70% of patients with
heart failure still die within 5 years of diagnosis. There is thus clear scope
for improving the treatment of patients with this condition. The CHARM programme
is designed to define the clinical benefits of the long-acting angiotensin II
type 1 (AT 1 ) receptor blocker, candesartan cilexetil, in a wide variety of
patients with symptomatic heart failure. Candesartan cilexetil will be evaluated
in three double-blind, randomized studies involving patients grouped according to
left ventricular function and ACE inhibitor tolerance/intolerance.
PMID- 28425814
TI - Verbal short-term memory and language impairments in Cantonese speakers after
stroke.
AB - PURPOSE: The study examined the relationship between verbal short-term memory
(STM) and language impairment in Cantonese speakers after stroke. It is
hypothesised that Cantonese speakers with left-hemisphere (LH) stroke would
perform worse than those with right hemisphere (RH) stroke and normal controls.
Specific linguistic factors of Cantonese might affect results in the tasks.
METHOD: Fifteen participants with LH stroke, 10 with RH stroke and 25 healthy
controls were tested with auditory-verbal immediate serial recall (ISR) tasks and
auditory linguistic tasks. All stroke participants were assessed with the
Cantonese version of Western Aphasia Battery (CAB). RESULT: The LH group
performed significantly worse than the RH and healthy control groups in the
auditory verbal ISR and auditory linguistic tasks. There were significant
lexicality, frequency and imageability effects in most tasks. Auditory
discrimination and word comprehension tasks, but not the auditory word
recognition task had correlations with ISR tasks. CONCLUSION: Verbal STM and
language performance of Cantonese-speakers with history of LH stroke were
inferior to RH stroke and healthy controls. The effects of lexicality, word
frequency and imageability on verbal STM memory performance were found. Cantonese
tones have effects on performance in auditory word recognition task, similar to
onset, nucleus and rime.
PMID- 28425818
TI - Immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae
protein D conjugate vaccine (PHiD-CV) according to different schedules in infants
in South Africa: a phase III trial.
AB - BACKGROUND: Limited clinical data exists to assess differences between various
infant pneumococcal conjugate vaccine schedules. In this trial, we evaluated
immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae
protein D conjugate vaccine (PHiD-CV) administered using 3 different immunization
schedules in HIV unexposed-uninfected infants in South Africa. METHODS: In this
phase III, open, single-center, controlled study (clinicaltrials.gov:
NCT00829010), 300 infants were randomized (1:1:1) to 1 of 3 PHiD-CV schedules: 3
dose priming and booster (3 + 1); 3-dose priming without booster (3 + 0); or 2
dose priming and booster (2 + 1). The booster was administered at 9-10 months of
age. immune responses were assessed up to 21 months after primary vaccination.
RESULTS: Post-priming antibody levels tended to be lower in the 2 + 1 group. At 6
months post-priming, antibody concentrations and opsonophagocytic activity titers
were within similar ranges after 2- or 3-dose priming. Robust increases were
observed pre- to post-booster in the 3 + 1 and 2 + 1 groups. CONCLUSIONS: PHiD-CV
was immunogenic when administered in different schedules. Post-booster responses
suggest effective immunological priming with both 2- and 3-dose primary series
and support administration of the booster dose at 9-10 months of age.
PMID- 28425819
TI - Early intervention in multiple sclerosis: how can we maximise patient prospects?
PMID- 28425820
TI - Metastatic soft tissue sarcoma: current treatment landscape and future
perspectives.
AB - INTRODUCTION: The therapeutic armamentarium for advanced soft tissue sarcoma
(STS) has increased over the last few years. Doxorubicin monotherapy or in
combination is now the established first line treatment. Beyond first line
treatment, no standard therapy has been established. Novel drugs have reached the
late-clinical stage development demonstrating to be effective in controlled
studies. While these novel treatments can be beneficial to a subset of patients,
even producing long lasting remissions, a significant fraction of the STS
population derives limited benefit. This is due to the fact that STS is a very
heterogeneous disease with different histopathologic features, biological
characteristics and clinical behaviour. Areas covered: The primary aim of this
review is to summarize data from recent phase III clinical trials in unselected
STS population, and to discuss their impact on the current clinical practice.
Phase I-II trials of special interest are discussed as well. Expert commentary:
Although our efforts in this research task are ongoing, the integration of
biological therapies, the anti-angiogenesis targeted treatments as well as
immunotherapy that may further improve the long term control of advanced STS are
of special clinical interest. Clinical management of advanced STS should be
tailored to each patient in order to optimize therapy.
PMID- 28425821
TI - L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing
chronic valproic acid treatment: A case report.
AB - Valproic acid is a broad-spectrum anticonvulsant that has also gained attention
in the psychiatric setting. With respect to safety, valproic acid may induce a
seemingly rare condition, hyperammonemia, which can induce a wide variety of
symptoms ranging from irritability to coma. The proposed mechanism of
hyperammonemia involves depletion of carnitine and overproduction of a toxic
metabolite, 4-en-valproic acid, both of which impair the urea cycle and thus
ammonia elimination. Carnitine is a commonly used antidote for acute intoxication
of valproic acid, but is not a therapeutic option for management of chronic
adults with adverse effects related to valproic acid. We herein report a case
involving a woman with epilepsy who developed hyperammonemia after a change in
her anticonvulsant therapy. She reported increased seizures and gastrointestinal
disturbances. Her ammonia, valproic acid, 4-en-valproic acid, and carnitine
levels were monitored. Her ammonia level was elevated and her carnitine level was
at the inferior limit of the population range. She was supplemented with
carnitine at 1 g/day. After 1 month, her ammonia level decreased, her carnitine
level increased, and her seizures were better controlled. Carnitine
supplementation was useful for reversal of her hyperammonemia, allowing her to
continue valproic acid for seizure control.
PMID- 28425822
TI - Association of hepatic vein Lipiodol tram-track sign during transcatheter
arterial chemoembolization with perioperative death.
AB - Objective To assess the relationship between the hepatic vein Lipiodol tram-track
sign during transcatheter arterial chemoembolization (TACE) and perioperative
death. Methods Patients treated for hepatic carcinoma at the Beijing Shijitan
Hospital, Capital Medical University from January 2010 to December 2015 were
retrospectively evaluated. The patients underwent hepatic TACE with Lipiodol. The
incidence of the hepatic vein Lipiodol tram-track sign, prognosis, and possible
risk factors were analyzed. Results A total of 5372 patients underwent hepatic
TACE and had complete available intraoperative imaging data. Among them, nine
patients showed the hepatic vein Lipiodol tram-track sign, including five who
died intraoperatively. The patients who died had liver metastasis from
hepatocellular carcinoma, cholangiocarcinoma, or breast cancer and had previously
received doxorubicin. The survivors had metastasis from gastric or colorectal
cancer and had not received doxorubicin. Conclusion Occurrence of the hepatic
vein Lipiodol tram-track sign during hepatic TACE is likely to result in
perioperative death.
PMID- 28425823
TI - Association between sleep time and depression: a cross-sectional study from
countries in rural Northeastern China.
AB - Objective To investigate the current situation of sleep status and examine its
association with depression among counties in rural areas of Liaoning Province,
China. Methods This cross-sectional study was conducted from January 2012 to
August 2013 in Northeast China. A total of 11,276 subjects aged >=35 years were
surveyed and completed the Patient Health Questionnaire-9; each participant
answered questions about their sleep duration. Results For individuals with a
sleep time of <=6, 6-7, 7-8, 8-9, and >=9 h, the respective risk of depression
was 10.8%, 3.7%, 2.6%, 2.7%, and 5.7% in subjects younger than 65 years old and
15.2%, 5.4%, 3.2%, 6.5%, and 8.6% in those 65 years old or older. Conclusion In
the rural population of Liaoning Province, sleep duration and depression are
closely related. Both short sleep and long sleep are risk factors for depression.
Optimizing sleep status may contribute to good physical and mental health.
PMID- 28425824
TI - Isolated ACL versus multiple knee ligament injury: associations with patient
characteristics, cartilage status, and meniscal tears identified during ACL
reconstruction.
AB - OBJECTIVES: The objectives of this study were to determine (1) if patients
undergoing reconstruction of an isolated anterior cruciate ligament (ACL) tear
had different characteristics (age, gender, body mass index [BMI]) than patients
undergoing ACL reconstruction (ACLR) with multiple knee ligament (MKL) tears and
(2) whether there was a difference in prevalence of articular cartilage injury
and meniscus tears between these two groups. METHODS: Patients undergoing primary
ACLR between February 2005 and June 2013 were identified through an ACLR
registry. Patients were grouped by whether they had an isolated ACL tear or an
ACL tear associated with another knee ligament tear. The study cohort was
analyzed to identify differences in patient characteristics and
cartilage/meniscus injury patterns between the groups. RESULTS: Of the 21,377
ACLR cases enrolled in the registry during the study period, 2.5% (n = 549) had
MKL tears. The MKL group had more males (73.2% vs. 62.8%, p < 0.001) than the
isolated ACL group. The MKL group also had a higher percentage of patients with a
BMI greater than 30 (31.1% vs. 22.7%, p = 0.0002). When adjusting for these
variables, any articular cartilage injury was equal in the two groups (OR = 1.01,
CI 0.82-1.25, p = 0.922), while medial femoral condyle injury was less common in
the MKL group (OR = 0.73, CI = 0.56-0.07, p = 0.28). The likelihood of any
meniscus tear was lower in the MKL group (OR = 0.56, CI = 0.47-0.67, p < 0.001)
as was the likelihood of medial meniscus tears (OR = 0.53, CI = 0.44-0.65, p <
0.001). CONCLUSIONS: When comparing patients with MKL tears versus isolated ACL
tears at ACLR, there was a higher percentage of males and patients with BMI over
30 in the MKL group. Medial femoral condyle articular cartilage injury, any
meniscus tear, and medial meniscus tears were less common in patients with MKL
injury compared to patients with isolated ACL tears.
PMID- 28425825
TI - Reviewing treatments and outcomes in the evolving landscape of ulcerative
colitis.
AB - Ulcerative colitis (UC) is a chronic inflammatory disease extending proximally
from the rectum to varying lengths of the colon that is characterized by
alternating cycles of relapse and remission. Therapeutic goals for patients with
active UC include induction and maintenance of remission and improvement in
quality of life, as well as mucosal healing, a clinical outcome recently
recognized in treatment guidance as being equally important. Mucosal healing is
associated with favorable long-term patient outcomes related to remission,
surgery, hospitalization, and quality of life. Given the increasing number of
newer therapies available, it is important to properly position the use of each
agent within the landscape of established UC therapies, evolving therapeutic
goals, and established guidelines. Extent of disease is important to consider
when selecting a treatment, as is an understanding of the short- and long-term
outcomes (e.g. corticosteroid-free remission, mucosal healing) associated with
each treatment. The purpose of this narrative review is to provide an overview of
newer therapies for the treatment of UC and how they may best fit in the evolving
landscape of UC.
PMID- 28425826
TI - Lung function and prevalence of respiratory symptoms in Norwegian crab processing
workers.
AB - BACKGROUND: Seafood processing workers have an increased risk of developing
occupational asthma. This has not been studied among Norwegian crab processing
workers, nor has the respiratory health of exposed workers been compared to a
control group. OBJECTIVES: Assessing the impact of working in the crab processing
industry on workers' respiratory health. DESIGN: A cross-sectional study of the
respiratory health in two types of crab processing workers compared to a control
group. METHODS: The study included 148 king crab (Paralithodes camtschaticus)
workers, 70 edible crab (Cancer pagurus) workers and 215 controls. Workers
answered a questionnaire and performed spirometry measurements. chi2 and Fishers
exact tests were performed on self-reported respiratory symptoms. Regression
analyses and t-tests were used to assess lung function values. RESULTS: Self
reported respiratory symptoms were higher among crab processing workers compared
to controls, and higher among king crab workers compared to edible crab workers.
There was no significant difference between crab processing workers and controls
in lung function measurements. Self-reported doctor-diagnosed asthma prevalence
was highest in the control group. CONCLUSIONS: Increased respiratory symptoms
reported by crab processing workers were not reflected in impaired lung function
values or asthma diagnose. We suggest a healthy worker effect among crab
processing workers in Norway.
PMID- 28425827
TI - Efficacy of glycine powder air-polishing combined with scaling and root planing
in the treatment of periodontitis and halitosis: A randomised clinical study.
AB - Introduction This study was performed to evaluate the clinical efficacy of using
the Perio-Flow device (Electro Medical Systems, Nyon, Switzerland) adjunctively
with mechanical instrumentation on periodontal parameters and halitosis.
Materials and Methods Sixty patients who presented with a 4- to 6-mm probing
pocket depth were recruited for the study. Patients were randomly assigned to
scaling and root planing (SRP) or SRP + glycine powder air-polishing (GPAP). For
both groups, the plaque index, gingival index, pocket depth, bleeding on probing,
and clinical attachment level scores were recorded at baseline and 1 month.
Volatile sulphur compounds (VSCs) were measured by a Halimeter (Interscan Corp.,
Chatsworth, CA, USA) at baseline, immediately after treatment, and at 7, 14, and
30 days. Results Both groups showed significantly lower plaque index, gingival
index, pocket depth, bleeding on probing, and clinical attachment level gain
scores at 1 month than at baseline. No significant differences were found between
the groups at any time point. The VSCs were significantly different at 1 month
compared with baseline in both groups. However, the intergroup comparisons of
VSCs were not statistically significant at any time point. Conclusion Within the
limits of this study, SRP is effective for treatment of periodontitis and
halitosis. However, using GPAP adjunctively with mechanical instrumentation has
no beneficial effects on halitosis or periodontal parameters.
PMID- 28425828
TI - Compliance to guidelines for the prescribing of antibiotics in acute infections
at Namibia's national referral hospital: a pilot study and the implications.
AB - BACKGROUND: Sub-optimal antibiotic prescribing remains a public health concern in
Namibia. The objective was to determine the level and predictors of compliance to
guidelines in the prescribing of antibiotics in acute infections at a national
referral hospital in Namibia to improve future prescribing. METHODS: An
analytical cross-sectional survey design. The clinical records of patients
receiving care were reviewed. Prescribing practices were assessed using a self-
administered questionnaire with reference to Namibia Standard Treatment
Guidelines (NSTG). RESULTS: The majority of prescriptions (62%) complied with the
NSTGs; however, lower than national targets (95%). Most prescriptions were
empiric and prescribers typically made reference to the NSTG (58%). Diagnosed
infections were principally respiratory infections (58%) and penicillins were the
most used antibiotics. Good concurrence between signs and symptoms with the
diagnosis indicated on the prescription - OR=5.2 (95% CI: 1.4, 19.2), a diagnosis
of upper respiratory tract (p=0.001), oral-dental OR=0.1(95% CI: 0.03,0.3) and
urogenital infections OR=0.3(95% CI: 0.1,0.95) and the prescribing of penicillins
(p=0.001) or combination antibiotics and amphenicols were independent predictors
of compliance to the NSTGs. The main behaviours associated with antibiotic
prescribing were patient influences, clinical state, and access to guidelines.
CONCLUSIONS: Compliance with NSTGs is suboptimal. Prescribing of combination
antibiotics, penicillins and diagnosis of oral dental, genitourinary and ear,
nose and throat infections were important predictors for NSTG compliance. There
is a need to implement antibiotic indicators and stewardship programmes, and
ensure access to NSTGs, to improve future antibiotic prescribing in Namibia.
PMID- 28425830
TI - Tryptase inhibitors: a patent review.
AB - INTRODUCTION: Tryptase is one of the main serine-proteinases located in the
secretory granules of mast cells, and is released through degranulation, which is
involved in the pathogenesis of allergic inflammatory disease, cardiovascular
diseases, lung fibrosis and tumor. Therefore, inhibitors targeting tryptase may
represent a new direction for the treatment of allergic inflammatory disease and
other diseases. Areas covered: In this article, we discussed the history and
development of tryptase inhibitors and described a variety of tryptase inhibitors
via their structures and biological importance in clinical studies and drug
development for tryptase-related diseases. Expert opinion: Initial tryptase
inhibitors based on indole structure as the hydrophobic substituent on a
benzylamine-piperidine template have low specificity and poor bioavailability.
Therefore, designing new and specific inhibitors targeting tryptase should be
involved in future clinical studies. Modifications toward indoles with varying N
substitution, introducing an amide bond, and growing the chain length contribute
to an increase in the specific selectivity and potency of tryptase inhibitors.
Tryptase has become the research hotspot to explore many related diseases.
Therefore, there has been growing appreciation for the potential importance of
the tryptase inhibitors as a target for treating these diseases.
PMID- 28425829
TI - Effects of dexmedetomidine versus midazolam for premedication in paediatric
anaesthesia with sevoflurane: A meta-analysis.
AB - Background Dexmedetomidine (DEX), an alpha2-adrenergic receptor agonist, produces
ideal sedation and early postoperative recovery for premedication in paediatric
surgery, reducing preoperative anxiety and facilitating smooth induction of
anaesthesia. We performed a meta-analysis to compare the effects of DEX and
midazolam (MDZ) in paediatric anaesthesia with sevoflurane. Methods PubMed, Ovid,
Web of Science, and Public Health Management Corporation were searched through
December 2016 for randomized controlled trials (RCTs) that compared DEX and MDZ
in children undergoing sevoflurane anaesthesia. The risk ratio (RR) with 95%
incidence interval (95%CI) was used for dichotomous variables. Results Twelve
RCTs involving 422 patients in the DEX group and 448 patients in the MDZ group
were included. Patients in the DEX group had a significantly lower incidence of
unsatisfactory sedation (RR [95%CI] = 0.71 [0.57-0.89]), unsatisfactory parental
separation (RR [95%CI] = 0.56 [0.35-0.87]), and rescue analgesia (RR [95%CI] =
0.52 [0.35-0.77]) than patients in the MDZ group. However, both groups had a
similar incidence of unsatisfactory mask acceptance, emergence agitation, and
postoperative nausea and vomiting. Conclusion Compared with MDZ, DEX is
beneficial in paediatric anaesthesia with sevoflurane because of its lower
incidence of unsatisfactory sedation, parental separation, and rescue analgesia.
PMID- 28425832
TI - Use of clear aligners in open bite cases: an unexpected treatment option.
AB - In open bite case treatments, a proper diagnostic differentiation is essential in
determining the appropriate corrective procedures. Dental open bites are
generally more responsive to treatment with orthodontics alone, whereas skeletal
open bites often require a combination of orthodontics and orthognathic surgery.
Patient selection and treatment principles for non-surgical open bite treatment
routinely include fixed appliances both labial or lingual. However, removable
clear aligners have gained a consistent popularity in the treatment of complex
cases including open bite malocclusions. In this article, the authors describe
three different clinical cases in which open bite cases had been satisfactorily
treated by using clear aligners.
PMID- 28425831
TI - Investigating the Phylogenetic Range of Gibberellin Biosynthesis in Bacteria.
AB - Certain plant-associated microbes can produce gibberellin (GA) phytohormones, as
first described for the rice fungal pathogen Gibberella fujikuroi and, more
recently, for bacteria, including several rhizobia and the rice bacterial
pathogen Xanthomonas oryzae pv. oryzicola. The relevant enzymes are encoded by a
biosynthetic operon that exhibits both a greater phylogenetic range and scattered
distribution among plant-associated bacteria. Here, the phylogenetic distribution
of this operon was investigated. To demonstrate conserved functionality, the
enzymes encoded by the disparate operon from X. translucens pv. translucens,
along with those from the most divergent example, found in Erwinia tracheiphila,
were biochemically characterized. In both of these phytopathogens, the operon
leads to production of the bioactive GA4. Based on these results, it seems that
this operon is widely dedicated to GA biosynthesis. However, there is intriguing
variation in the exact product. In particular, although all plant pathogens seem
to produce bioactive GA4, rhizobia generally only produce the penultimate
hormonal precursor GA9. This is suggested to reflect their distinct interactions
with plants, because production of GA4 counteracts the jasmonic-acid-mediated
defense response, reflecting the importance of wounds as the entry point for
these phytopathogens, whereas such suppression presumably is detrimental in the
rhizobial symbiotic relationship.
PMID- 28425833
TI - Management of missing second premolars using miniscrews: an elective solution for
critical anchorage conditions.
AB - Growing patients with congenital missing second premolars should be accurately
evaluated in order to establish an appropriate treatment plan. The decision
whether to close or maintain spaces in dental arches caused by missing teeth
should be based on the consideration of biomechanical factors and the aesthetic
traits of individual patients. Accordingly, the choice of closing spaces requires
an adequate consideration of biomechanical principles in order to avoid
detrimental effects on the occlusion and profile. The effective use of titanium
miniscrews for immediate loading, combined with efficient sliding mechanics,
represents an elective way of successfully treating such cases. The aim of this
article is to describe the procedure and highlight its advantages by giving
details of a clinical case coupled with the results of a long-term follow-up.
PMID- 28425834
TI - Rift Valley fever vaccines: an overview of the safety and efficacy of the live
attenuated MP-12 vaccine candidate.
AB - INTRODUCTION: Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease
endemic to Africa and the Arabian Peninsula. High rates of abortion among
infected ruminants and hemorrhagic fever in infected humans are major public
health concerns. Commercially available veterinary RVF vaccines are important for
preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries;
however, RVFV outbreaks continue to occur frequently in endemic countries in the
21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed
for both animal and human vaccination. This vaccine strain is well attenuated,
and a single dose induces neutralizing antibodies in both ruminants and humans.
Areas covered: This review describes scientific evidences of MP-12 vaccine
efficacy and safety, as well as MP-12 variants recently developed by reverse
genetics, in comparison with other RVF vaccines. Expert commentary: The
containment of active RVF outbreaks and long-term protection from RVF exposure to
infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will
allow immediate vaccination of susceptible animals in case of an unexpected RVF
outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF
control in endemic regions.
PMID- 28425835
TI - Enzymatic synthesis and protein adsorption properties of crystalline nanoribbons
composed of cellulose oligomer derivatives with primary amino groups.
AB - The in vitro enzymatic synthesis of cellulose and its derivatives has attracted
growing interest for fabricating novel cellulose-based supramolecular assemblies
with unique physicochemical and functional properties. However, their potential
biomedical applications have not been sufficiently demonstrated despite their
useful features of designable structures and tailor-made surface functionalities.
Herein, we demonstrated the production of crystalline nanoribbons composed of
cellulose oligomer derivatives with primary amino groups via cellodextrin
phosphorylase-catalyzed single-step reactions using alpha-d-glucose l-phosphate
monomers and 2-aminoethyl-beta-d-glucoside primers. Then, the fundamental
properties of protein adsorption onto the surface-aminated nanoribbons were
systematically investigated. It was found that the primary amino groups on the
nanoribbon surfaces effectively attracted negatively charged proteins but not
positively charged ones. Furthermore, it was demonstrated that the nanoribbons
did not show apparent cytotoxicity against cultured cells. Taken together, our
findings open a new avenue for the facile production of cellulose-based
supramolecular assemblies with tailor-made functionality for future biomedical
applications.
PMID- 28425836
TI - Development and validation of a multi-analyte method for the regulatory control
of carotenoids used as feed additives in fish and poultry feed.
AB - Carotenoids are used in animal nutrition mainly as sensory additives that
favourably affect the colour of fish, birds and food of animal origin. Various
analytical methods exist for their quantification in compound feed, reflecting
the different physico-chemical characteristics of the carotenoid and the
corresponding feed additives. They may be natural products or specific
formulations containing the target carotenoids produced by chemical synthesis. In
this study a multi-analyte method was developed that can be applied to the
determination of all 10 carotenoids currently authorised within the European
Union for compound feedingstuffs. The method functions regardless of whether the
carotenoids have been added to the compound feed via natural products or specific
formulations. It is comprised of three steps: (1) digestion of the feed sample
with an enzyme; (2) pressurised liquid extraction; and (3) quantification of the
analytes by reversed-phase HPLC coupled to a photodiode array detector in the
visible range. The method was single-laboratory validated for poultry and fish
feed covering a mass fraction range of the target analyte from 2.5 to 300 mg kg
1. The following method performance characteristics were obtained: the recovery
rate varied from 82% to 129% and precision expressed as the relative standard
deviation of intermediate precision varied from 1.6% to 15%. Based on the
acceptable performance obtained in the validation study, the multi-analyte method
is considered fit for the intended purpose.
PMID- 28425837
TI - Calprotectin levels in rheumatoid arthritis and their correlation with disease
activity: a meta-analysis.
AB - OBJECTIVE: We evaluated the relationship between calprotectin levels and
rheumatoid arthritis (RA), and the correlation between plasma/serum calprotectin
and RA activity. METHODS: We searched PUBMED, EMBASE, and Cochrane databases and
performed meta-analyses comparing plasma/serum or synovial fluid calprotectin
levels in RA patients and controls, and correlation coefficients between
calprotectin levels and disease activity for 28 joints (DAS28) as well as C
reactive protein (CRP) in RA patients. RESULTS: Sixteen studies including 849 RA
patients and 266 controls were available for meta-analysis. Meta-analysis showed
that calprotectin levels were significantly higher in the RA group than in the
control group (SMD = 2.337, 95% CI = 1.544-3.130, p < 1.0 * 10-8). Stratification
by rheumatoid factor (RF) status revealed significantly elevated calprotectin
levels in the RF-positive RA group compared to that of the RF-negative RA group
(SMD = 0.574, 95% CI = 0.345-0.804, p = 9.2 * 10-7). Meta-analysis of correlation
coefficients identified a significant positive correlation between calprotectin
levels and CRP or DAS28 (correlation coefficient for CRP = 0.566, 95% CI = 0.512
0.615, p < 1.0 * 10-8; correlation coefficient for DAS28 = 0.438, 95% CI = 0.269
0.518, p = 2.5 * 10-6). Calprotectin levels in synovial fluid were significantly
higher in the RA group than in the control group (SMD = 2.891, 95% CI = 1.067
4.715, p = 0.002). CONCLUSIONS: Our meta-analysis demonstrates that circulating
and synovial fluid calprotectin levels are high in patients with RA, and that
circulating calprotectin levels positively correlate with RA activity.
PMID- 28425838
TI - Attending to emotional expressions: no evidence for automatic capture in the dot
probe task.
AB - Research on automatic attention to emotional faces offers mixed results.
Therefore we examined validity effects for facial expressions of different
emotions (compared to neutral faces) with a dot-probe paradigm in seven studies
(total N = 308). Systematic variations of type of emotion, CTI, task, cue size,
and masking allow for a differentiated assessment of attentional capture by
emotions and possible moderating factors. Results indicate a general absence of
emotional validity effects as well as a lack of significant interactions with
either of the manipulated factors, indicating that facial expressions of emotions
do not capture attention in a fully automatic fashion. These findings suggest
that situational and contextual factors have to be taken into account when
investigating attentional capture of emotional faces.
PMID- 28425840
TI - Standardization of Criteria Defining Periodontal Ligament Stem Cells.
PMID- 28425841
TI - Adipocyte hypertrophy-hyperplasia balance contributes to weight loss after
bariatric surgery.
AB - Predictors of weight loss responses are not well-defined. We hypothesized that
adipose tissue phenotypic features related to remodeling would be associated with
bariatric surgery weight loss responses. Visceral and subcutaneous adipose
tissues collected from patients during bariatric surgery were studied with flow
cytometry, immunohistochemistry, and QRTPCR, and results correlated with weight
loss outcomes. Age, male sex, and a diagnosis of type 2 diabetes were associated
with less weight loss. Adipocyte size was increased and preadipocyte frequency
was decreased in visceral adipose tissue from diabetic subjects. Decreased
adipose tissue preadipocyte frequency was associated with less weight loss in
women but not men. These data suggest that phenotypic features of adipose tissue
remodeling may predict responses to weight loss interventions.
PMID- 28425842
TI - Estradiol does not directly regulate adipose lipolysis.
AB - The mechanisms by which estradiol modulates adipose lipolysis are poorly
understood. We sought to measure basal and beta3-stimulated indices of lipoysis
(FFAs, glycerol) in vivo in E2 deficient or supplemented rats, and ex vivo with
direct acute E2 exposure. For 2 weeks, ovariectomized (OVX) and OVX rats treated
with a daily oral dose of E2 (OVX E2) were pairfed to SHAM controls (n = 12 per
group). Adipocyte size was modestly (~40%) increased in OVX rats, but did not
reach significance (p = 0.2). After 2 weeks, half of the animals in each group
received an in vivo injection of saline or 1 mg/kg of the beta3 agonist CL 316,
243. Serum FFA concentrations, but not glycerol, were lower in OVX and OVX E2
rats compared with SHAM controls (p = 0.02). A significant CL response was
present in all groups (p<0.001) and HSL activation was unaffected by OVX or OVX
E2 in retroperitoneal (r.p.) or inguinal (iWAT) adipose depots in vivo. Ex vivo,
CL increased FFA and glycerol accumulation in the media as well as HSL
phosphorylation by several fold in r.p. and iWAT explants, but responses from OVX
and OVX E2 rats were comparable to SHAMs. To assess whether E2 can directly
affect lipolysis, r.p. and iWAT tissue was treated with E2, CL or E2 + CL for 2,
4 or 8 hours using adipose tissue organ culture. CL stimulated FFA release
(p<0.001), but was unaffected by E2. Overall, our results indicate that E2 does
not directly regulate adipose tissue lipolysis.
PMID- 28425843
TI - The dual role of BMP4 in adipogenesis and metabolism.
AB - BMP4 has a well-established role in triggering commitment of mesenchymal stem
cells into the osteogenic and adipogenic linage. We recently described an
additional dual function in adipogenesis: after promoting the formation of both
white and brown pre-adipocytes, Bmp4 drives terminal differentiation into mature
white rather than brown fat cells. Besides this, Bmp4 seems to have a dual role
in metabolism either promoting or repressing oxidative metabolism in a cell
context dependent manner.
PMID- 28425844
TI - The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in
obesity.
AB - Obesity is closely associated with metabolic diseases including type 2 diabetes.
One hallmark characteristics of obesity is chronic inflammation that is
coordinately controlled by complex signaling networks in adipose tissues.
Compelling evidence indicates that reactive oxygen species (ROS) and its related
signaling pathways play crucial roles in the progression of chronic inflammation
in obesity. The pentose phosphate pathway (PPP) is an anabolic pathway that
utilizes the glucoses to generate molecular building blocks and reducing
equivalents in the form of NADPH. In particular, NADPH acts as one of the key
modulators in the control of ROS through providing an electron for both ROS
generation and scavenging. Recently, we have reported that glucose-6-phosphate
dehydrogenase (G6PD), a rate-limiting enzyme of the PPP, is implicated in adipose
tissue inflammation and systemic insulin resistance in obesity. Mechanistically,
G6PD potentiates generation of ROS that augments pro-inflammatory responses in
adipose tissue macrophages, leading to systemic insulin resistance. Here, we
provide an overview of cell type- specific roles of G6PD in the regulation of ROS
balance as well as additional details on the significance of G6PD that
contributes to pro-oxidant NADPH generation in obesity-related chronic
inflammation and insulin resistance.
PMID- 28425845
TI - Nck2, an unexpected regulator of adipogenesis.
AB - The regulation of adipose tissue expansion by adipocyte hypertrophy and/or
hyperplasia is the topic of extensive investigations given the potential
differential contribution of the 2 processes to the development of numerous
chronic diseases associated with obesity. We recently discovered that the loss-of
function of the Src homology domain-containing protein Nck2 in mice promotes
adiposity accompanied with adipocyte hypertrophy and impaired function, and
enhanced adipocyte differentiation in vitro. Moreover, in severely-obese human's
adipose tissue, we found that Nck2 expression is markedly downregulated. In this
commentary, our goal is to expand upon additional findings providing further
evidence for a unique Nck2-dependent mechanism regulating adipogenesis. We
propose that Nck2 should be further investigated as a regulator of the reliance
of white adipose tissue on hyperplasia versus hypertrophy during adipose tissue
expansion, and hence, as a potential novel molecular target in obesity.
PMID- 28425846
TI - Alterations to adipose tissue morphology during inflammatory arthritis is
indicative of vasculopathology in DBA/1 mice.
AB - The physiologic function of adipose tissue is altered by the host's inflammatory
response; the implications for maintaining human health and regulating
inflammation-associated disease progression are ill defined. However, this cannot
be investigated in humans, therefore the use of animal models is required. With
the aim to determine morphological and molecular alterations to perivascular and
organ-associated adipose tissues during inflammatory arthritis, collagen-induced
arthritis (CIA) was established in male DBA/1 mice. Emerging evidence from this
study signposts CIA in the DBA/1 mouse as a model that is relevant to study the
development and treatment of early cardiovascular pathology associated with
inflammatory arthritis. Here, we show global morphological changes in adipose
tissue and the thoracic aorta in animals induced with CIA compared with the non
immunized controls. In CIA, we concluded that the increased cell count in PVAT
was, at least in part, caused by an ingress and/or expansion of macrophages that
had a mixed phenotype. A substantial increase of galectin-3 was expressed in PVAT
from mice with CIA. Galectin-3 is elevated in the blood of patients with CVDs,
however, it has never before been measured in PVAT in rodents or humans. Here,
PVAT-associated galectin-3 is identified as a potential biomarker for detecting
early vascular pathology in CIA and a promising candidate for translation to RA.
PMID- 28425847
TI - Form(ul)ation of adipocytes by lipids.
AB - Lipids have the potential to serve as bio-markers, which allow us to analyze and
to identify cells under various experimental settings, and to serve as a clinical
diagnostic tool. For example, diagnosis according to specific lipids that are
associated with diabetes and obesity. The rapid development of mass-spectrometry
techniques enables identification and profiling of multiple types of lipid
species. Together, lipid profiling and data interpretation forge the new field of
lipidomics. Lipidomics can be used to characterize physiologic and
pathophysiological processes in adipocytes, since lipid metabolism is at the core
of adipocyte physiology and energy homeostasis. A significant bulk of lipids are
stored in adipocytes, which can be released and used to produce energy, used to
build membranes, or used as signaling molecules that regulate metabolism. In this
review, we discuss how exhaust of lipidomes can be used to study adipocyte
differentiation, physiology and pathophysiology.
PMID- 28425848
TI - The contribution of bone marrow-derived cells to the human adipocyte pool.
AB - White adipose tissue is a remarkably expandable organ with results in the last
decade showing that human white adipocytes are continuously turned over during
the entire life-span. Data primarily in murine models have demonstrated that
adipocytes are derived from precursors present mainly in the perivascular areas
of adipose tissue but their precise origin remains unclear. Subsets of cells
present in bone marrow display a multipotent differentiation capacity which has
prompted the hypothesis that bone marrow-derived cells (BMDCs) may also
contribute to the adipocyte pool present in peripheral fat depots. This notion
was initially demonstrated in a murine transplantation model, however, subsequent
animal studies have been conflicting resulting in a debate of whether BMDCs
actually differentiate into adipocytes or just fuse with resident fat cells. This
controversy was recently resolved in 2 studies of human subjects undergoing bone
marrow transplantation. Using a combination of different assays these data
suggest that bone marrow contributes to at least 10% of the adipocyte pool. This
proportion is doubled in obesity, suggesting that BMDCs may constitute a reserve
pool for adipogenesis, particularly upon weight gain. This review discusses the
possible mechanisms and relevance of these findings for human pathophysiology.
PMID- 28425849
TI - Age-dependent obesity and mitochondrial dysfunction.
AB - Aging is associated with progressive visceral white adipose tissue (WAT)
expansion both in human and mouse. Importantly, WAT enlargement is initiated
early in life, suggesting that molecular mechanisms underlying age-dependent
obesity are activated at early stages of lifetime. Our recent study found that
age-dependent obesity was associated with a specific decline in mitochondrial
complex IV activity, which leads to reduced fatty acid oxidation and subsequent
adipocyte hypertrophy. At the molecular level, global mitochondrial complex IV
inhibition was driven by hypoxia-inducible factor-1alpha (HIF1alpha)-mediated
repression of some of its key subunits, including cytochrome c oxidase 5b
(Cox5b). In this commentary, we compare age-dependent WAT responses with those
observed in the high fat diet model of extreme obesity. Furthermore, we discuss
the potential scenarios that could initiate age-dependent WAT expansion as well
as the mechanisms by which HIF1alpha could be activated in WAT.
PMID- 28425850
TI - A novel and robust method for testing bimodality and characterizing porcine
adipocytes of adipose tissue of 5 purebred lines of pig.
AB - Adipocyte sizes from adipose tissue of mature animals form a bimodal
distribution, thus reporting mean cell size is misleading. The objectives of this
study were to develop a robust method for testing bimodality of porcine
adipocytes, describe the size distribution with an informative metric, and
statistically test hypertrophy and appearance of new small adipocytes, possibly
resulting from hyperplasia or lipid filling of previously divided fibroblastic
cells. Ninety-three percent of adipose samples measured were bimodal (P <
0.0001); therefore, we describe and propose a method of testing hyperplasia or
lipid filling of previously divided fibroblastic cells based upon the probability
of an adipocyte falling into 2 chosen competing "bins" as adiposity increases. We
also conclude that increased adiposity is correlated positively with an adipocyte
being found in the minor mode (r = 0.46) and correlated negatively with an
adipocyte being found in the major mode (r = -0.22), providing evidence of either
hyperplasia or lipid filling of previously divided fibroblastic cells. We
additionally conclude that as adiposity increases, the mode of the major
distribution of cells occurs at a larger diameter of adipocyte, indicating
hypertrophy.
PMID- 28425852
TI - Discovery of Novel 2-Amino-5-(Substituted)-1,3,4-Thiadiazole Derivatives: New
Utilities for Colon Cancer Treatment.
AB - BACKGROUND: Colon cancer is one of the most widespread disease, the mortality
rate is high due to cancer metastasis and the development of drug resistance. In
this regards, new chemotherapeutic agents with specific mechanisms of action and
significant effect on patient's survival are the new era for the colon cancer
drug development. OBJECTIVE: The main objective of present study was to design,
synthesize of a novel series of 1,3,4-thiadiazole derivatives (VR1 to VR35) and
screen them against HT-29 human colon cancer cell line. METHOD: Newly 1,3,4
thiadiazole scaffold were designed, synthesized and further, characterized by
FTIR, NMR (1H and 13C), MS and elemental analyses. Before the synthesis,
molecular dynamic simulation and ADME studies were performed to find out the most
potent lead compounds. Later, SRB assay using HT-29 cells and ELISA assays were
performed to explore activity and molecular targets of VR24 and VR27 and find out
whether in silico data had a similar pattern in the molecular level. RESULTS: The
results of docking study revealed that both VR24 and VR27 had interaction energy
>-5 kcal/mol with various assigned molecular targets and the ligand-protein
complexes were found to be stable with IL-6. The computational analysis of
molecules showed good ADMET profiling. Later, the in vitro anticancer study was
conducted where VR24 and VR27 were found to be active against HT-29 cells
(GI50<10 uM). Finally, ELISA assays revealed that both the compounds had higher
inhibition properties to various biomarker of colon cancer like IL-6 and COX-2.
CONCLUSION: Collectively, these result suggested that VR24 and VR27 inhibited the
assigned molecular targets, imparting their ameliorative effects against colon
cancer. Due to these encouraging results, we concluded that both VR24 and VR27
may be effective against colon cancer therapy in future.
PMID- 28425851
TI - Altered structure and function of adipose tissue in long-lived mice with growth
hormone-related mutations.
AB - A major focus of biogerontology is elucidating the role(s) of the endocrine
system in aging and the accumulation of age-related diseases. Endocrine control
of mammalian longevity was first reported in Ames dwarf (Prop1df) mice, which are
long-lived due to a recessive Prop1 loss-of-function mutation resulting in
deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin.
Following this report, several other GH-related mutants with altered longevity
have been described including long-lived Snell dwarf and growth hormone receptor
knockout mice, and short-lived GH overexpressing transgenic mice. One of the
emerging areas of interest in these mutant mice is the role of adipose tissue in
their altered healthspan and lifespan. Here, we provide an overview of the
alterations in body composition of GH-related mutants, as well as the altered
thermogenic potential of their brown adipose tissue and the altered cellular
senescence and adipokine production of their white adipose tissue.
PMID- 28425853
TI - Evaluation of the in vitro Chemosensitivity and Correlation with Clinical
Outcomes in Lung Cancer using the ATP-TCA.
AB - BACKGROUND AND OBJECTIVE: Multiple drug resistance (MDR) to chemotherapeutic
agents often leads to a failure to respond to chemotherapy. We utilized an in
vitro chemosensitivity test to identify sensitive and effective chemotherapeutic
drugs and further elucidated the correlation between the in vivo chemosensitivity
and clinical outcomes. METHODS: Here, we evaluated the in vitro chemosensitivity
and MDR of 120 lung cancer patients to eight singledrug chemotherapies and of 291
lung cancer patients to seven chemotherapy regimens using an ATP-based tumor
chemosensitivity assay (ATP-TCA). Additionally, the chemosensitivity profiles of
lung adenocarcinoma patients (284 cases) and lung squamous cell carcinoma
patients (90 cases) to these single-drug and chemotherapy regimens were compared.
Furthermore, the correlations between the chemosensitivity and clinical outcomes
were investigated in 16 stage III squamous cell carcinoma patients. RESULTS AND
CONCLUSION: PTX (51.7%), TXT (43.3%), GEM (12.5%), PTX+DDP (62.5%), TXT+L-OHP
(54.3%) and VP-16+DDP (16.2%) had the highest in vitro chemosensitivity rates.
Approximately 31.7% of patients developed resistance to all eight single-drug
chemotherapies, and 25.8% of patients displayed resistance to all seven
chemotherapy regimens. In addition, lung squamous cell carcinoma was
significantly more sensitive to GEM and MTA+DDP than lung adenocarcinoma
(P<0.05). Further analysis showed that patients with higher drug sensitivity
tended to have longer disease-free survival (18 months vs. 8.5 months) than
patients displaying drug resistance (P<0.05). These results suggest that the
implementation of in vitro drug susceptibility testing before chemotherapy can
effectively prevent the occurrence of primary drug resistance and inappropriate
drug treatment.
PMID- 28425854
TI - Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking
Studies of 1,3,4-oxadiazole Analogues.
AB - BACKGROUND: 1,3,4-Oxadiazole heterocycles possess a broad spectrum of biological
activities. They were reported as potent cytotoxic agents and tubulin inhibitors;
hence it is of great interest to explore new oxadiazoles as cytotoxic agents
targeting tubulin polymerization. OBJECTIVE: Two new series of oxadiazoles (5a-h
and 12a-h) were synthesized, structurally related to the heterocyclic linked aryl
core of IMC-038525, NSC 776715, and NSC 776716, with further modification by
incorporating methylene linker. METHOD: The 2,5-disubstituted-1,3,4-oxadiazoles
(5a-h and 12a-h) were synthesized by refluxing an equimolar mixture of the
intermediates [(4) and (8a-d)] and aromatic aldehydes in water-ethanol system
using sodium bisulphite catalyst. The cytotoxicity evaluation was carried out
according to the National Cancer Institute (NCI US) Protocol, while the tubulin
polymerization assay kits from Cytoskeleton TM(bk011p) was used to perform an in
vitro tubulin polymerization assay. RESULTS: 2-(5-{[(4-Chlorophenyl)amino]methyl}
1,3,4-oxadiazol-2-yl)phenol (5f) and 2-[(2,4-dichlorophenoxy) methyl]-5-(3,4
dimethoxyphenyl)-1,3,4-oxadiazole (12c) showed maximum cytotoxicity with the mean
percent growth inhibitions (GIs) of 71.56 and 72.68 respectively at 10 uM drug
concentrations. Both the compounds (5f and 12c) showed superior cytotoxicity than
clinically prevalent anticancer drugs, Imatinib and Gefitinib in one dose assay.
The compound 12c showed promising results in five dose assay, with GI50 values
varies between 1.61 and >100 uM. Furthermore, the compounds, 5f and 12c also
inhibited the polymerization of tubulin with, an IC50 of 2.8 and 2.2 uM,
respectively. CONCLUSION: The oxadiazoles reported herein are tubulin inhibitors
and cytotoxic agents. These findings will be helpful in future drug design of
more potent tubulin inhibitor cytotoxic agents.
PMID- 28425855
TI - Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy.
AB - The aberrant proliferation of tumor cells and abundant vasculature in tumor
tissues are closely correlated with receptors that are specifically dysregulated
in tumor cells. These tumor-associated targets are critical in early diagnosis
and therapy selection. Ligands such as antibodies, proteins, polypeptides and
polysaccharides that specifically bind to these targets can significantly improve
the detection and cure rate when used as tumor imaging probes or anti-tumor
agents. Compared to other targeting ligands, peptides have attracted increasingly
more attention in tumor diagnostics and therapeutics because of their small
sizes, high affinity, stability, ease of modification and low immunogenicity.
Several peptide-based imaging probes and therapeutic agents have already been
used in clinical trials. This review summarizes some of the tumor-associated
targets and their corresponding peptides, as well as the potential of these
peptides in cancer treatment.
PMID- 28425856
TI - Apicidin Inhibited Proliferation and Invasion and Induced Apoptosis via
Mitochondrial Pathway in Non-small Cell Lung Cancer GLC-82 Cells.
AB - BACKGROUND: Apicidin, as an inhibitor of histone deacetylase, showed a wide range
of antiproliferative activity against various cancer cell lines. Apicidin has
also been reported to induce apotosis via Fas/Fas ligand. Yet few studies have
been focused on mitochondrial pathway for its anti-tumor activity. OBJECTIVE: In
this study, we evaluated its involved mitochondrial mechanism against non-small
cell lung cancer GLC-82 cells. METHOD: Apicidin was isolated from the mangrove
endophtic fungi Fusarium sp. by solvent extraction and column chromatography. Its
structure was elucidated by MS and NMR spectroscopic data, and comparison of
those data with published data. Furthermore, anti-tumor activity and
mitochondrial pathway of apicidin against GLC-82 cells were studied. RESULTS:
Apicidin was obtained from secondary metabolites of Fusarium sp., and it showed
potent inhibitory activity against GLC-82 cells with the IC50 value of 6.94 +/-
0.27 uM. Furthermore, apicidin suppressed proliferation and invasion, and induced
apoptosis via mitochondrial pathway in GLC-82 cells, including loss of DeltaPsim,
release of cytochrome c from mitochondria, activation of caspase-9 and -3, and
cleavage of poly-ADP-ribose polymerase. CONCLUSION: Apicidin, an inhibitor of
histone deacetylase obtained from the mangrove endophytic fungi Fusarium sp., not
only inhibited proliferation and invasion of GLC-82 cells, but also induced
apoptosis via the mitochondrial pathway.
PMID- 28425857
TI - Antioxidant Properties of Fractions for Unripe Fruits of Capsicum annuum L. var.
Conoides.
AB - BACKGROUND: Capsicum plant, especially for C. annuum, is an abundant resource for
bioactive antioxidants, but few studies have examined the unripe fruit part of
the Capsicum plant. OBJECTIVE: MeOH extract of unripe fruits of C. annuum L. var.
conoides (UFCA) was chromatographed over a silica gel column using a gradient of
CH2Cl2/MeOH as eluent to produce 9 fractions. Antioxidant activities are
evaluated along with cell viabilities of 9 fractions of UFCA. METHOD: The
antioxidant properties were analyzed in terms of total phenol content (TPC),
total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
scavenging, 2,2-azinobis (3-ethyl-benzothiazoline-6- sulfonic acid) (ABTS)
radical scavenging, ferric reducing, and ferrous ion-chelating ability. The cell
viability of human oral cancer cells (Ca9-22) was measured by 3-(4,5
dimethylthiazol-2-yl)-(3-carboxymethoxyphenyl)-2- (4-sulphophenyl)-2H-tetrazolium
(MTS) assay. RESULTS: Except for TFC, fractions (Frs.) 1 and 2 showed the lowest
level of these antioxidant properties. Frs. 3 to 9 showed dose-responsive
induction for antioxidant effects. Fr. 8 and Fr. 5 respectively showed the
highest levels of TPC and TFC for 1162 +/- 11 gallic acid equivalents (GAE)
(mg)/UFCA (g) and 1295 +/- 32 quercetin equivalents (QCE) (mg)/UFCA (g). The cell
viability of Fr. 3 was moderately decreased (78.2%) while those of Frs. 4, 5, and
9 were dramatically decreased (55.6, 57.8, and 46.8%, respectively) in oral
cancer Ca9-22 cells. UFCA-derived 14 compounds/mixtures derived from Frs. 1, 2,
3, 4, and 8 displayed differential antioxidant performance for these analyses.
CONCLUSION: Taken together, fractions of UFCA displayed diverse antioxidant and
anticancer effects for oral cancer cells. Some fractions of UFCA may be potent
natural antioxidant supplements for antioral cancer cell treatment.
PMID- 28425858
TI - Nano-encapsulation of Dietary Phytoconstituent Capsaicin on Emulsome: Evaluation
of Anticancer Activity Through the Measurement of Liver Oxidative Stress in Rats.
AB - BACKGROUND: Excessive reactive species derived from oxygen and nitrogen leads to
oxidative damage to tissue and organs. Capsaicin (CAP), a pungent component found
in red pepper can prevent oxidative stress. OBJECTIVE: The aim of the present
work was to evaluate the protective effects of CAP loaded nano-emulsomes (EML)
against the oxidative stress of rat livers induced through sodium fluoride (NaF).
METHOD: EML was prepared by thin film hydration method that is development of
thin lipid film followed by hydration and sonication. EML was characterized by
Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD)
techniques. EML was evaluated for drug entrapment, in vitro drug release, and in
vivo study. RESULTS: In vitro drug release study of optimized formulation showed
that 50% of CAP was released within 50.21 min while 85% CAP was released in 227.4
min. Single oral dose of free CAP and CAP loaded EML were given to rats 2 hour
after NaF administration. Membrane of hepatic cells was damaged by NaF and it was
judged by the estimation of lipid peroxidation, reactive oxygen species (ROS),
and catalase activity. The administration of CAP loaded EML 2 hr after NAF
consumption showed significant decrease in ROS level compared to free CAP. EML
containing CAP was more effective in comparison to free CAP in controlling the
lipid peroxidation that is thiobarbituric acid substance augmentation in liver by
the treatment of NaF. The administration of CAP loaded EML showed significant
increase in catalase activity compared to free CAP administration. CONCLUSION:
The results clearly demonstrated that CAP loaded EML may be accepted as an
effective therapeutic formulation in preventing oxidative damage.
PMID- 28425859
TI - Synthesis, Characterization, and Inducing Tumor Cell Apoptosis of Two Ru(II)
Complexes Containing Guanidinium as Ligands.
AB - DESCRIPTION: Two new ruthenium(II) complexes containing guanidinium as ligands,
[Ru(dip)2 (L1)]3+ (Ru1) and [Ru(dip)2(L2)]3+ (Ru2) (dip=4,7-diphenyl-1,10
phenanthroline; L1=1-(4-(1H-imidazo[4,5- f][1,10]phenanthrolin-2
yl)phenyl)guanidine cation; L2 = 1-(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)
phenyl)guanidine cation) have been synthesized and characterized. Both complexes
display higher cytotoxicity against several cancer cell lines compared to
cisplatin and are less cytotoxic on the nontumorigenic cell line LO2.
Intracellular distribution studies show that these complexes are selectively
localized in the cytoplasm. FINDINGS: Further analysis revealed that Ru1 and Ru2
had no obvious effects on the cell cycle and induced apoptosis in HeLa cells via
the mitochondrial pathway, which involved reactive oxygen species (ROS)
accumulation, mitochondrial dysfunction, and Bcl-2 family member activation.
Taken together, the two complexes have the potential to be utilized as anticancer
agents.
PMID- 28425860
TI - A Novel Recombinant Multi-Epitope Vaccine Could Induce Specific Cytotoxic T
Lymphocyte Response In Vitro and In Vivo.
AB - BACKGROUND: Malignant tumor is still one of the important diseases worldwide,
cytotoxic CD8+ T lymphocytes (CTLs) play an important role in killing tumor
cells. OBJECTIVE: To enhance the immune response of our previously identified HLA
A2-restricted CTL epitopes, we designed a multiepitope YL66. METHOD: The fusion
protein GST-YL66 and DNA vaccine pcDNA3.1(+)-YL66 were used to induce CTLs from
human peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donors and
and in HLA-A2.1/Kb transgenic(Tg) mice. and the activity of induced CTLs were
tested by IFN-gamma relesde ELISPOT assay and LDH cytotoxicity assay. RESULTS:
GST-YL66 induced CTL could lysis tumor cells and release IFN-gamma both in vitro
and in vivo, and pcDNA3.1(+)-YL66 could also induce significant CTL response in
vivo. CONCLUSION: The designed fusion multiepitope YL66 could be used as a
vaccine against patients with tumors expressing COX-2 and/or MAGE-4.
PMID- 28425861
TI - Role of Cysteine Residues in Regulation of Peptidyl-prolyl cis-trans Isomerase
Activity of Wheat Cyclophilin TaCYPA-1.
AB - BACKGROUND: The wheat cyclophilin, TaCYPA-1, shows peptidyl-prolyl cis-trans
isomerase (PPIase) activity. However, the significance of different cysteine
residues in regulation of PPIase activity of this protein has not been
investigated. OBJECTIVES: The main objective of this study was to analyze the
role of different disulphide linkages in redox mechanisms that modulate the
PPIase activity of TaCYPA-1. METHOD: Site-directed mutants of TaCYPA-1 were
generated by substituting cysteine residues at positions -40 and -122 with serine
and -126 with proline. The recombinant proteins were expressed in Escherichia
coli and purified. The effect of Cu2+ and N-ethylmaleimide was studied on PPIase
activity of the purified recombinant cyclophilins for analyzing the role of
different cysteine residues in the modulation of enzyme activity. The changes in
secondary structure of TaCYPA-1 and its mutants were analysed by recording far UV
CD spectra. The effect of different cysteine substitutions on thermotolerance of
E. coli was studied by monitoring the cell growth at 47 degrees C after 2 h, 3 h
and 5 h of heat stress. RESULTS: The catalytic efficiencies (Kcat/Km) of TaCYPA
1C40S (0.37 X 106 M-1 s-1) and TaCYPA- 1C122S (0.31 X 106 M-1 s-1) were
significantly lower as compared to the native TaCYPA-1 (1.33 X 106 M-1 s-1),
whereas Kcat/Km of the double mutant TaCYPA-1C40S/C122S was significantly higher
(2.36 X 106 M-1 s-1). Compared to the wild-type TaCYPA-1, the different mutants
also showed differential sensitivity to Cu2+. Furthermore, the results of this
study also revealed that despite lacking PPIase activity, the mutant TaCYPA
1C126P was able to confer partial protection against heat stress. CONCLUSION:
This study revealed that mutation of different cysteine residues in TaCYPA-1
results in differential effect on PPIase activity. It was also observed that of
the two pairs of cysteine residues i.e. Cys40/Cys168 and Cys122/Cys126, the
latter appears to play major role in redox regulation of TaCYPA-1. The mutant
TaCYPA-1C126P, though lacking PPIase activity, was able to impart partial
tolerance to heat stress in E. coli, suggesting other functions besides cis to
trans isomerisation. This study, therefore, provides new insights into the
regulation of plant cyclophilins.
PMID- 28425862
TI - The Impact of IL-17 in Atherosclerosis.
AB - Atherosclerosis is a chronic vascular disease in which atherosclerotic plaques
develop in the arterial wall. It is believed that inflammation plays a major role
in atherosclerotic formation and progression. Thus, atherosclerosis can be
considered as an inflammatory disease of the arterial vessel. Mouse model
demonstrated that T and B cell deficiency reduces the atherosclerotic burden in
the formation of an atherosclerotic lesion. CD4+ T helper cells (Th), such as Th1
cells known being the major CD4+ T cell subtype found in mouse models of
atherogenesis, increase plaque formation caused by oxLDL. IL-17 (also known as IL
17A) was produced by T cells or by a unique subset of T helper cells. IL-17
producing T cells express interferon- gamma (IFN-gamma), an important regulator
of immune function, which is highly expressed in atherosclerotic lesions, defying
their neat characteristics as Th17 cells. Regulation of Th17 signal pathway may
play a significant role in the pathogenesis of multiple inflammatory and
autoimmune disorders, such as atherosclerosis. In this review, the structural
features of IL-17 family and their roles involved in atherosclerosis are
described.
PMID- 28425863
TI - Targeted Drug Delivery Based on Gold Nanoparticle Derivatives.
AB - Drug delivery systems are effective and attractive methods which allow
therapeutic substances to be introduced into the body more effectively and safe
by having tunable delivery rate and release target site. Gold nanoparticles
(AuNPs) have a myriad of favorable physical, chemical, optical, thermal and
biological properties that make them highly suitable candidates as non-toxic
carriers for drug and gene delivery. The surface modifications of AuNPs
profoundly improve their circulation, minimize aggregation rates, enhance
attachment to therapeutic molecules and target agents due to their nano range
size which further increases their ability to cross cell membranes and reduce
overall cytotoxicity. This comprehensive article reviews the applications of the
AuNPs in drug delivery systems along with their corresponding surface
modifications. The highlighting results obtained from the preclinical trial are
promising and next five years have huge possibility move to the clinical setting.
PMID- 28425864
TI - Editorial: Phytochemicals and their Effects on Human Health.
PMID- 28425865
TI - Editorial: HIV and Antiretroviral Drugs: Current Status and New Challenges.
PMID- 28425866
TI - Recent Development of Oridonin Derivatives with Diverse Pharmacological
Activities.
AB - Oridonin is one of the major components isolated from Isodon rubescens, a
traditional Chinese medicine, and it has been confirmed to exhibit many kinds of
biological activities including anticancer, anti-inflammation, antibacterial and
so on. However, the poor pharmaceutical property limits the clinical applications
of oridonin. So many strategies have been explored in the purpose of improving
the potencies of oridonin, and structure modification is one thus way. This
review outlines the landscape of recent development of oridonin derivatives with
diverse pharmacological activities, mainly focusing on the biological properties,
structure-activity relationships, and mechanism of actions.
PMID- 28425867
TI - Chemokines and Relevant microRNAs in the Atherogenic Process.
AB - Chemokines play a significant role in initial and advanced steps of
atherogenesis. In early steps, chemokines control the adhesion of leukocytes to
endothelial cells (ECs) followed by transmigration of monocytes and their
deposition in the intima where they differentiate to proinflammatory macrophages.
Except for proinflammatory activity, chemokines are responsible for homeostasis
and homing of progenitor cells. Recently, microRNAs (miRs) were found to control
expression and activity of chemokines in ECs, vascular smooth muscle cells
(VSMCs), and macrophages at different steps of atherogenesis. Expression of the
proatherogenic chemokine CXCL1 is suppressed by miR-181 that down-regulates
nuclear transcription factor NF-kB stimulation in ECs therefore weakening the
adhesiveness of the endothelium for monocytes. MiR-126 activates the endothelial
production of a chemokine CXCL12 via self-multiplying feedback loop to promote re
endothelialization and support lesion stability. MiR-155 is proatherogenic by
induction of the inflammatory chemokine CCL2 in macrophages. In fact, chemokines,
their receptors, and relevant miRs form a complex network that exerts pro- and
anti-inflammatory properties in vascular cells during different steps of
atherogenic process. Obtaining new information about complicated relations
between miRs and chemokines may create prerequisites for the development of novel
approaches to treat atherosclerosis.
PMID- 28425868
TI - Pomegranate as a Possible Treatment in Reducing Risk of Developing Wound Healing,
Obesity, Neurodegenerative Disorders, and Diabetes Mellitus.
AB - Four distinguished although overlying stages make up the methodical procedure of
wound healing, which are hemostasis, inflammation, proliferation and remodelling.
Multiple sclerosis (MS) is described as an incessant inflammatory central nervous
system disease, and is linked with neurodegeneration, demyelination, as well as
susceptibility to oxidative pressure. Obesity signifies a swiftly developing
danger to the wellbeing of populations in a rising number of nations. Usually
called diabetes mellitus (DM) by medical practitioners, diabetes details a
collection of metabolic diseases within which the individual has raised blood
glucose, either due to an insufficiency of insulin generation, or the lack of
suitable response by the body to insulin, or both. Conventionally, the
pomegranate, as well as its flowers, leaves, fruit juice and tree bark, has been
applied in the treatment of conditions including acidosis, haemorrhage, diarrhoea
and microbial contagions. Extracts of pomegranate have been established to
contain intense anti-inflammatory, antioxidant as well as antitumor features in
vivo as well as ex vivo. Of late, beneficial consequences of decrease of fat have
been illustrated employing the pomegranate as well as its extracts. Several of
the favourable consequences are associated with the availability of anthocyanins,
tannins, and considerably elevated amounts of antioxidants, as well as flavonoids
and polyphenols. A summary of the endeavours applied to deal with the possible
advantages of the pomegranate towards healing wounds, Alzheimer's disease (AD),
diabetes mellitus (DM) and obesity, as well as an appraisal of the efficiency of
intervention through the pomegranate and its extracts is provided in this
article.
PMID- 28425869
TI - Development of a Chitosan-based Nanoparticle Formulation for Ophthalmic Delivery
of Honokiol.
AB - BACKGROUND: Retinal neovascularization (NV) is the leading cause of blindness in
the majority of ocular diseases. Several treatment approaches have been developed
for retinal NV; of these methods, instillation of nanoparticles into the
conjunctival sac has shown potential for retinal NV treatment because it does not
cause physical damage and is easy to operate. METHODS: In this study, honokiol
loaded chitosan/sulfobutylether-beta-cyclodextrin nanoparticles (HKCS- NPs) were
prepared for ophthalmic drug delivery systems. An inclusion complex of honokiol
and sulfobutylether-beta-cyclodextrin was used to incorporated insoluble honokiol
into chitosan nanoparticles, which were prepared through ionotropic gelation.
RESULTS: HK-CS-NPs featured a spherical surface with a narrow size distribution
of polydispersity index less than 0.250, a mean size range of 373-523 nm, a
positive surface charge of +19.9 to +24.2 mV, and an entrapment efficiency of
84.92%. In vitro release studies showed an initial burst release phase and a
sustained release phase of nanoparticles. Moreover, in vivo study showed that HK
CS-NPs exhibited good ocular tolerability and could improve ophthalmic
bioavailability of honokiol. In particular, the maximum concentration of honokiol
after administration of HK-CS-NPs was enhanced by 1.65 times compared with that
after instillation of the honokiol suspension alone. CONCLUSION: This study
proposes HK-CS-NPs as a potential ophthalmic delivery system.
PMID- 28425870
TI - iPreny-PseAAC: Identify C-terminal Cysteine Prenylation Sites in Proteins by
Incorporating Two Tiers of Sequence Couplings into PseAAC.
AB - BACKGROUND: Occurring at the cysteine residue in the C-terminal of a protein,
prenylation is a special kind of post-translational modification (PTM), which may
play a key role for statin in altering immune function. Therefore, knowledge of
the prenylation sites in proteins is important for drug development as well as
for in-depth understanding the biological process concerned. OBJECTIVE: Given a
query protein whose C-terminal contains some cysteine residues, which one can be
of prenylation or none of them can be prenylated? METHODS: To address this
problem, we have developed a new predictor, called "iPreny-PseAAC", by
incorporating two tiers of sequence pair coupling effects into the general form
of PseAAC (pseudo amino acid composition). RESULTS: It has been observed by four
different cross-validation approaches that all the important indexes in
reflecting its prediction quality are quite high and fully consistent to each
other. CONCLUSION: It is anticipated that the iPreny-PseAAC predictor holds very
high potential to become a useful high throughput tool in identifying protein C
terminal cysteine prenylation sites and the other relevant areas. To maximize the
convenience for most experimental biologists, the webserver for the new predictor
has been established at http://app.aporc.org/iPreny-PseAAC/, by which users can
easily get their desired results without needing to go through the mathematical
details involved in this paper.
PMID- 28425871
TI - The Journey of the Non-Vascular Relief for Migraine: From 'Triptans' To 'Ditans'.
AB - Migraine is a recurrent, disabling, complex and highly prevalent neurological
disorder. The mystery behind the cause of migraine is continuously evolving,
according to the scientific understanding of the disease. This growing
understanding helps to identify novel therapeutic targets for the management of
migraine to treat the ailing migraineurs. The role of serotonin (5HT) in migraine
is recognized to be the cornerstone for the currently available therapeutic
options namely ergot alkaloids and triptans. The role of mediators such as
Calcitonin Gene-Related Peptide (CGRP), nitric oxide and excitatory
neurotransmitter glutamate, has been realized and ignited the development of
drugs targeting these factors. Lasmiditan, known as a Neurally Active Anti-
Migraine Agent (NAAMA) is a specific 5HT1F agonist, developed as a new group
named as 'ditans'. The drug was designed and developed to meet the unmet needs of
currently available medications to circumvent the vascular adverse effects.
Having a group of drugs with a nonvascular mechanism of action, devoid of
unwanted effects with a different spectrum of indication and contraindications,
is the need of the hour to expand the armamentarium available to tackle acute
migraine attack.
PMID- 28425872
TI - Increase in human immunodeficiency virus 1 diversity and detection of various
subtypes and recombinants in north-eastern Brazil.
AB - PURPOSE: Diverse human immunodeficiency virus 1 (HIV-1) subtypes and circulating
recombinant forms are found in Brazil. The majority of HIV-1 molecular
epidemiological studies in Brazil have been conducted in the southern and south
eastern regions of the country, although several recent studies in the north
eastern region have addressed this issue. The objective of this study was to
molecularly characterize HIV-1 circulating in Pernambuco, north-eastern Brazil.
METHODOLOGY: A total of 64 samples were collected from 2002 to 2003, and another
103 were collected from 2007 to 2009. The protease and partial reverse
transcriptase regions of the HIV-1 polymerase-encoding (pol) gene were sequenced,
and subtyping, recombination and phylogenetic analyses were performed.Results/Key
findings. Subtype B (60.9 %) was found to be predominant, followed by HIV-1 F
(31.4 %). Several BF recombinants (4.2 %), and BC and AG recombinants were also
identified. The intra-subtype genetic diversity was estimated to be 0.065 (sd+/
0.004) for HIV-1 B and 0.055 (sd+/-0.004) for HIV-1 F, reflecting a greater
accumulation of mutations in subtype B (P<0.01). More codons were found to be
under positive selective pressure in samples collected from 2007 to 2009, from
individuals with a T-cell count>=200 cells mm-3 and from women. Coalescence data
indicated that the subtype F population has been continuously expanding.
CONCLUSIONS: HIV-1 shows high genetic diversity in the state of Pernambuco. Thus,
additional molecular evaluations of circulating strains will provide a better
understanding of the epidemic and may lead to more effective preventive
strategies.
PMID- 28425873
TI - Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in
extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using
Xpert MTB/RIF.
AB - BACKGROUND: Tuberculosis (TB) is a serious public health problem in developing
countries such as Pakistan. Rapid diagnosis of TB and detection of drug
resistance are very important for timely and appropriate management of multidrug
resistant TB (MDR-TB). OBJECTIVE: The purpose of this study was to determine the
diagnostic efficacy of the Xpert MTB/RIF assay for rapid diagnosis of TB and
detection of rifampicin (RIF) resistance in extrapulmonary and smear-negative
pulmonary TB suspects. METHODS: A total of 98 bronchoalveolar lavage fluid (BALF)
and 168 extrapulmonary specimens were processed by Xpert MTB/RIF. Culture results
are considered as the gold standard for diagnosis of TB, and drug susceptibility
testing for detection of RIF resistance. Diagnostic efficacy was measured in
terms of sensitivity, specificity and positive and negative predictive values.
RESULTS: The Xpert MTB/RIF assay detected 40 (40.8 %) of 98 BALF of presumptive
pulmonary TB and 60 (35.7 %) of 168 extrapulmonary specimens. Sensitivity and
specificity of the Xpert MTB/RIF assay for detection of TB was 86 and 88.4 %,
respectively. The positive predictive value was 71.5 % while negative predictive
value was 95.1 %. CONCLUSION: The Xpert MTB/RIF assay is a rapid and simple
technique with high sensitivity and specificity for diagnosing TB and detecting
drug resistance in extrapulmonary and smear-negative TB cases.
PMID- 28425874
TI - In vitro and in vivo assessments of Rhodomyrtus tomentosa leaf extract as an
alternative anti-streptococcal agent in Nile tilapia (Oreochromis niloticus L.).
AB - PURPOSE: Rhodomyrtustomentosa is a Thai medicinal plant that has been attracting
attention for its remarkable antibacterial properties against Gram-positive
pathogenic bacteria. The purpose of this study was to evaluate the antibacterial
properties of R. tomentosa leaf extract against Streptococcus agalactiae and
Streptococcus iniae isolated from infected tilapia. METHODOLOGY: The anti
streptococcal activity of R. tomentosa was determined using broth microdilution
assays. RESULTS: The extract demonstrated strong antibacterial activity against
the fish pathogens, with minimum inhibitory concentrations (MICs) ranging from
7.8-62.5 ug ml-1. It was found to possess a dose-dependent bacteriostatic effect
on this organism. Scanning electron microscopy revealed irregular and long chains
of swollen cells, as well as corkscrew shapes andincomplete separation of cell
division of S. agalactiae cells following the treatment at sub-MIC. Moreover, S.
agalactiae cells pre-treated with the extract became more sensitive to oxidative
stress induced by H2O2 than the untreated cells. Based on the mortality of Nile
tilapia after intraperitoneal infection of S. agalactiae at median lethal dose
(LD50), the pre-treated cells caused a significant (P<0.01) reduction in
mortality of S. agalactiae-infected Nile tilapia. CONCLUSION: The results
suggested that R. tomentosa could be further developed as a simple and effective
agent for the treatment of streptococcosis in Nile tilapia.
PMID- 28425875
TI - Occurrence of qnrB1 and qnrB12 genes, mutation in gyrA and ramR, and expression
of efflux pumps in isolates of Klebsiella pneumoniae carriers of blaKPC-2.
AB - PURPOSE: The occurrence of quinolone-resistance genes (qnrA, qnrB and qnrS), the
presence of mutations in gyrA, gyrB and parC, as well as the expression of efflux
pumps (acrB and acrF) and mutations in the gene ramR. METHODOLOGY: Were
investigated in 30 blaKPC-2-positive isolates of Klebsiella pneumoniae taken from
infection and colonization in hospital patients from Recife-PE, Brazil. The
detection of the qnr, acrB and acrF genes and analysis of the mutations in ramR
and the quinolone-resistance-determining regions of gyrA, gyrB and parC were
performed by PCR followed by DNA sequencing. RESULTS: Among the isolates
analysed, 73.3 % (n=22) presented the qnrB gene. For the DNA sequencing, six
isolates (K3-A2, K12-A2, K25-A2, K27-A2, K19-A2 and K3-C2) were selected and the
qnrB1 and qnrB12 variants were detected. This is the first ever report, to the
best of our knowledge, of the presence of qnrB12 in K. pneumoniae. This is also
the first report, to the best of our knowledge, of the presence of qnrB1 or
qnrB12 with blaKPC-2 in K. pneumoniae in Brazil. Mutations were observed in gyrA
S83 and in ramR. All isolates presented genes for the acrB and acrF efflux pumps
and the reverse transcription PCR performed showed that the pumps were being
expressed. CONCLUSION: KPC-2-positive isolates colonizing patients, which also
showed qnrB, mutation in gyrA and efflux pumps, may be important reservoirs for
disseminating these resistance mechanisms in the hospital environment.
PMID- 28425876
TI - Characterization of the translation elongation factor 1-alpha gene in a wide
range of pathogenic Aspergillus species.
AB - PURPOSE: We aimed to evaluate the resolving power of the translation elongation
factor (TEF)-1alpha gene for phylogenetic analysis of Aspergillus species.
METHODOLOGY: Sequences of 526 bp representing the coding region of the TEF-1alpha
gene were used for the assessment of levels of intra- and inter-specific
nucleotide polymorphism in 33 species of Aspergillus, including 57 reference,
clinical and environmental strains. RESULTS: Analysis of TEF-1alpha sequences
indicated a mean similarity of 92.6 % between the species, with inter-species
diversity ranging from 0 to 70 nucleotides. The species with the closest
resemblance were A. candidus/A. carneus, and A. flavus/A. oryzae/A. ochraceus,
with 100 and 99.8 % identification, respectively. These species are
phylogenetically very close and the TEF-1alpha gene appears not to have
sufficient discriminatory power to differentiate them. Meanwhile, intra-species
differences were found within strains of A. clavatus, A. clavatonanicus, A.
candidus, A. fumigatus, A. terreus, A. alliaceus, A. flavus, Eurotium amstelodami
and E. chevalieri. The tree topology with strongly supported clades (>=70 %
bootstrap values) was almost compatible with the phylogeny inferred from analysis
of the DNA sequences of the beta tubulin gene (BT2). However, the backbone of the
tree exhibited low bootstrap values, and inter-species correlations were not
obvious in some clades; for example, tree topologies based on BT2 and TEF-1alpha
genes were incompatible for some species, such as A. deflectus, A. janus and A.
penicillioides. CONCLUSION: The gene was not phylogenetically more informative
than other known molecular markers. It will be necessary to test other genes or
larger genomic regions to better understand the taxonomy of this important group
of fungi.
PMID- 28425877
TI - Me, the Editor-In-Chief and the Puzzle Work.
PMID- 28425878
TI - Medical Education in Portugal.
PMID- 28425879
TI - Continuing Medical Education in Portugal: A New Era?
PMID- 28425880
TI - [Narrative Medicine: An Optative Course at the Faculty of Medicine of Lisbon].
PMID- 28425881
TI - [On the Future of Portuguese Physician-Scientists].
PMID- 28425882
TI - Associations Between the Big Five Personality Traits and a Medical School
Admission Interview.
AB - INTRODUCTION: Personality has became popular in medical student's selection.
However, few research exists about the association between the big five
personality traits and the existent medical school selection tools. Our aim was
to study which personality traits were selected by a medical school admission
interview. MATERIAL AND METHODS: One hundred ninety four graduate applicants that
had applied to the Faculty of Medicine of the University of Porto through the
graduate entry approach, after ranked on previous achievement, were interviewed
between the academic years of 2011 and 2013. From these, 181 (93.3%) answered to
the NEO Five-Factor Inventory that assesses high order personality traits of
openness to experience, conscientiousness, extraversion, agreeableness and
neuroticism. Admission interview corresponded to the second phase of the
seriation process. Every applicant was interviewed and scored by three
interviewers on seven dimensions asesssed by Lickert scale (1-10). Interview
score was the sum of the dimensions. Linear mixed effects model and respective
regression coefficients were used to estimate the association between personality
traits from each interviewer's score. Final models were adjusted for gender,
interviewers and previous achievement. RESULTS: Openness to experience (Beta =
0.18: CI 95%: 0.05; 0.30) had the strongest association with interview score
followed by the interaction effect between the extraversion and conscientiousness
traits (Beta = 0.14; CI 95%: 0.02; 0.25). Also, applicants scored higher when
their gender was opposite to the interviewers. DISCUSSION: Previous achievement
and interview score had no association. CONCLUSION: Our admission interview
selected different personality traits when compared to other selection tools.
Medical schools should be aware of the implications of the adopted selection
tools on the admitted medical student's personality because it can help providing
beneficial interventions.
PMID- 28425883
TI - Transition from Secondary School to Medical School: The Role of Self-Study and
Self-Regulated Learning Skills in Freshman Burnout.
AB - INTRODUCTION: The transition from secondary to higher education is a challenging
and demanding period for medical students. The ability to manage study time
effectively and to be a self-regulated learner is essential to cope with the
exponential growth of knowledge in medical education. Thus, the purpose of our
study was to measure self-regulated learning skills and self-study across
secondary higher education transition and to explore its effect on academic
burnout in the first year of medical school. MATERIAL AND METHODS: We collected
data from 102 (43%) freshman medical students on self-regulated learning,
academic achievement, and hours of self-study/week relative to last year of
secondary school (at the beginning of academic year) and the first year of
medical school (at the end of academic year). Burnout data was collected at the
end of academic year. RESULTS: Among the 102 participants, 12% were at risk of
burnout. Self-directedness at secondary school and higher education, and
strategies for learning and assessment at higher education were protective
factors against academic burnout. However, secondary selfdirectedness has an
indirect effect on academic burnout mediated by self-directedness in the first
year of medical school. In addition, self-study during class period was a risk
factor for burnout. CONCLUSION: Our results support the premise that students
experience mental health problems from an early stage at medical school.
Empowering medical students to develop strategies for learning assessment and
self-direction will help them manage their learning and, consequently, promote
their well-being. Finally, we found that it is not academic performance that
influences burnout but the time dedicated to study.
PMID- 28425884
TI - A Brief Course on Clinical Communication Skills: A Multi- Centered Study.
AB - INTRODUCTION: This paper describes and analyses the results of a multicenter
course on clinical communication skills with the use of the learning in small
groups, patient actors and feedback. The aim of the course was to encourage
participants to develop a more effective clinical communication to recognize the
different manifestations of the same disease in different patients (disease
versus illness). MATERIAL AND METHODS: The course was applied to third and fourth
year medical students in three Brazilian universities and one university in
Portugal. The evaluation was performed using scales regarding the participants'
point of view, multiple choice questionnaire, a self-efficacy and attitudinal
questionnaire. RESULTS: The study was conducted in 69 participants at the four
universities. The overall evaluation of the course (from 1 - 5) was 4.70 (SD
0.494), the self-evaluation on participation was 4.07 (SD 0.671); and the
evaluation about the use of simulated patients 4.51 (SD 0.501). The multiple
choice questionnaire and self-efficacy scale showed significant improvement.
DISCUSSION: The course methods had an excellent evaluation by students regardless
of the context in which the course has been applied. Furthermore, it allowed an
improvement on the knowledge and attitude of students regarding clinical
communication. CONCLUSION: It was possible to develop a multi-centric learning
strategy for clinical communication with a high evaluation by students who came
from a Portuguese university in a cooperation project with teachers from
Brazilian universities.
PMID- 28425885
TI - An Objective Structured Clinical Exam to Assess Semiology Skills of Medical
Students.
AB - INTRODUCTION: Mastery of history taking and physical exam skills is a key
competence of medical students. Objective Structured Clinical Examinations are
the gold standard to assess these competencies, but their implementation in
Portugal is poorly documented. We describe the implementation and our seven years
experience with a high-stakes Objective Structured Clinical Examination to assess
these skills in the School of Medicine, University of Minho. MATERIAL AND
METHODS: Our Objective Structured Clinical Examination is in place since 2010 and
has been subject to continuous improvements, including the adoption of a standard
setting procedure and an increase in the number of stations. RESULTS: Grades in
our exam are well distributed and discriminate among students. History taking
grades are lower and have remained stable throughout the years while physical
examination scores have risen. The exam is reliable, with internal consistency
above 0.45 and a G-coefficient of 0.74. It is also feasible, with a total testing
time of approximately 20 hours for 140 students, and the involvement of 18
standardized patients and 18 faculty assessors. More importantly, it was able to
engage the students, who recognize its importance. DISCUSSION: The most important
validity criterion of our, and any Objective Structured Clinical Examination,
would be predictive validity,the ability to predict the performance of students
in the clinical context. CONCLUSION: Our approach to a high-stakes Objective
Structured Clinical Examination shows that it is feasible, reliable, valid and
fair and can be implemented with success in the Portuguese setting.
PMID- 28425886
TI - An Overview of Teaching Communication of Bad News in Medical School: Should a
Lecture be Adequate to Address the Topic?
AB - INTRODUCTION: Delivering bad news is very common in medical daily practice.
Several studies have shown a lack of effective communication skills amongst
medical students, particularly concerning how to deliver bad news. The SPIKES
protocol allows communicating bad news in a 6-step method. The aim of this study
is to investigate the perspective of students related to this subject. MATERIAL
AND METHODS: A 45 minute lecture "Breaking Bad News" was given to 160 students in
the fifth and sixth years of the Medicine course, using the SPIKES' protocol
training. After the lecture, an online survey was given to all students, and a
cross-sectional and descriptive analysis of data extracted from survey was
undertaken. RESULTS: Fifty-four students (21% of overall) answered the online
survey. Eighty three percent said that theme should have an important role in
their further daily medical practice, and most of students rated the physicians'
role as challenging. Sixty percent of students expressed that communicating bad
news was an integral part of the medical course curriculum. Regarding the SPIKES'
protocol, 48% felt that the first step would be the easiest to put in practice,
and 40% felt that the fifth step related to "Emotions" would be the most
difficult. DISCUSSION: In general, the students would like to gain competencies
in breaking bad news using a practical approach Conclusions: Students highly
valued theoretical and practical approaches in teaching of communication of bad
news. Therefore, we encourage a combination approach in pre-graduate medical
education.
PMID- 28425887
TI - Undergraduate Teaching in Geriatrics and Pediatrics in Portuguese Medical
Schools: An Observational Study.
AB - INTRODUCTION: Motivated by the contracting nature of the Portuguese age pyramid,
and thereby the ever increasing geriatric population, the aim of this study was
to compare the number of European Credit Transfer and Accumulation System Credits
dedicated to Geriatrics with Pediatrics in Portuguese Medical Schools. MATERIAL
AND METHODS: An observational, descriptive and cross-sectional study was
conducted and included six Portuguese Medical Schools that have six years of
training and a total of 360 credits. The study plans were obtained from the
medical schools' websites or requested. Schools were grouped in modular/classic
teaching methodology and the courses were categorized in mandatory/optional and
specific/related. The credits of Geriatrics and Pediatrics were compared.
RESULTS: Four schools had classical methodology and two had a modular one.
Overall, they had more credits dedicated to Pediatrics than Geriatrics. Three
schools offered mandatory courses specifically oriented to Geriatrics (1.5 - 8
credits) compared to all schools mandatory courses courses on Pediatrics (5.7 -
26.5 credits). The ratio of averages of mandatory specific courses
(Pediatrics/Geriatrics) was 12.4 in the classical and 1.5 in the modular group.
DISCUSSION: Pediatrics teaching has revealed to be superior to Geriatrics in all
categories. Based on our results, we consider the Portuguese Geriatrics'
undergraduate teaching sub-optimal. CONCLUSION: Nowadays, geriatric population is
quantitatively similar to pediatric population. Efforts should be made to
adequate Geriatrics teaching to our reality in order to provide a more adequate
health care to this age group.
PMID- 28425888
TI - [Satisfacao com o Internato Medico em Portugal].
AB - INTRODUCTION: In the last years, the global context of medical education and
Medical Residency programs in Portugal suffered substantial changes. The primary
objective of this study was to evaluate and characterize medical residents
satisfaction with medical residency programs in Portugal and to identify features
that could be improved. MATERIAL AND METHODS: We utilized as model the survey
Postgraduate Hospital Educational Environment Measure that has been developed in
the United Kingdom and is speci cally targeted to medical residents. The survey
was translated and adapted to the Portuguese reality. The survey was available
online during April and May of 2016. RESULTS: A total of 3456 responses were
obtained, corresponding to a response rate of 35%. Endocrinology/Nutrition,
Cardiology, Anesthesiology, Family Physician and Gastroenterology were the
specialties in which the degree of satisfaction was higher, while Forensic
Medicine, Medical Oncology, Internal Medicine, General Surgery and Pneumology
showed the lowest level of satisfaction. DISCUSSION: This study presented a high
response rate when compared to previous studies. Portuguese medical residents
presented high levels of satisfaction. Depending on year of medical residency,
region, type of specialty and type of hospital marked asymmetries were noticed.
CONCLUSION: The survey s results should constitute in the future a support tool
for the implementation of local and national measures relating to the medical
residency. It is advisable to regularly conduct satisfaction surveys to medical
residents.
PMID- 28425890
TI - Biomedical Simulation: Evolution, Concepts, Challenges and Future Trends.
AB - Biomedical simulation is an effective educational complement for healthcare
training, both at undergraduate and postgraduate level. It enables knowledge,
skills and attitudes to be acquired in a safe, educationally orientated and
efficient manner. In this context, simulation provides skills and experience that
facilitate the transfer of cognitive, psychomotor and proper communication
competences, thus changing behavior and attitudes, and ultimately improving
patient safety. Beyond the impact on individual and team performance, simulation
provides an opportunity to study organizational failures and improve system
performance. Over the last decades, simulation in healthcare had a slow but
steady growth, with a visible maturation in the last ten years. The simulation
community must continue to provide the core leadership in developing standards.
There is a need for strategies and policy development to ensure its coordinated
and cost-effective implementation, applied to patient safety. This paper reviews
the evolutionary movements of biomedical simulation, including a review of the
Portuguese initiatives and nationwide programs. For leveling knowledge and
standardize terminology, basic but essential concepts in clinical simulation,
together with some considerations on assessment, validation and reliability are
presented. The final sections discuss the current challenges and future
initiatives and strategies, crucial for the integration of simulation programs in
the greater movement toward patient safety.
PMID- 28425889
TI - SOAP Methodology in General Practice/Family Medicine Teaching in Practical
Context.
AB - INTRODUCTION: Medical records in General Practice/Family Medicine are an
essential information support on the health status of the patient and a
communication document between health professionals. The development of
competencies in General Practice/Family Medicine during pre-graduation must
include the ability to make adequate medical records in practical context. As of
2012, medicine students at the University of Beira Interior have been performing
visits using the Subjective, Objective, Assessment and Plan - SOAP methodology,
with a performance evaluation of the visit, with the aim to check on which
Subjective, Objective, Assessment and Plan - SOAP aspects students reveal the
most difficulties in order to define improvement techniques and to correlate
patient grade with tutor evaluation. MATERIAL AND METHODS: Analysing the
evaluation data for the 2015 - 2016 school year at the General Practice/Family
Medicine visit carried out by fourth year students in medicine, comparing the
averages of each item in the Subjective, Objective, Assessment and Plan - SOAP
checklist and the patient evaluation. RESULTS: In the Subjective, Objective,
Assessment and Plan - SOAP, 29.7% of students are on the best grade quartile,
37.1% are on the best competencies quartile and 27.2% on the best patient grade
quartile. 'Evolution was verified/noted' received the worst grades in Subjective,
'Record of physical examination focused on the problem of the visit' received the
worst grades in Objective, 'Notes of Diagnostic reasoning / differential
diagnostic' received de worst grades in Assessment and 'Negotiation of aims to
achieve' received the worst grades in Plan. The best tutor evaluation is found in
'communication'. DISCUSSION: Only one single study evaluated student's
performance under examination during a visit, with similar results to the present
one and none addressed the patient's evaluation. CONCLUSION: Students revealed a
good performance in using the Subjective, Objective, Assessment and Plan - SOAP.
The findings represent the beginning of the introduction of the Subjective,
Objective, Assessment and Plan - SOAP to the students. This evaluation breaks
ground towards better ways to teach the most difficult aspects.
PMID- 28425891
TI - Teaching Psychology in Medicine: The Context, Methodologies and Doctor's
Professional Identity.
AB - INTRODUCTION: Teaching Psychology in medical curriculum has been the subject of
numerous dissertations that focus on the relevance of this knowledge for doctors,
at a general level. METHODS: A non-systematic review of the relevant literature,
particularly from the last decade, as well as national and international
recommendations addressing the need for integration of behavioural and social
sciences in medical training, was performed. RESULTS: The literature supports the
existence of preconceptions and negative attitudes towards the role of psychology
in medical education, demonstrated by research in various european and american
universities. The socio-cultural context, the different methodologies and
barriers experienced by teachers in medical education are listed and provide the
matrix for a more comprehensive discussion of the development of the doctor's
identity. CONCLUSION: Revisiting the experience of many years of teaching Medical
Psychology, it is considered that the process of integration of this curricular
area should occur horizontally and vertically throughout the course, stressing
the need for the pedagogical training of teachers. Concepts that arise from
personal reflection, adjusted to the reality of our education and the basic
principles that guide it, are elaborated in order to integrate the teaching of
Psychology in Medicine, emphasizing its importance and utility in the
competencies and abilities of future doctors.
PMID- 28425892
TI - The weakening of public health: A threat to population health and health care
system sustainability.
PMID- 28425893
TI - An examination of perceived health care availability and unmet health care need
in the City of Toronto, Ontario, Canada.
AB - OBJECTIVES: Although timely access to health care is a top priority, a burgeoning
body of research highlights the important role of neighbourhood environments on
unmet health care needs. This study aimed to examine an association between
perceptions of neighbourhood availability of health care services and experience
of unmet health care needs by gender in an urban city setting. METHODS: A total
of 2338 participants from the Neighbourhood Effects on Health and Well-being
(NEHW) study, between 25 and 64 years of age and dwelling in the City of Toronto,
Ontario, Canada, were included in the analyses. Four different logistic
regression models stratified by gender were used to examine the relationship
between neighbourhood health care availability and unmet health care need as well
as the impact of neighbourhood perception of health care availability on the
three different types of unmet needs. RESULTS: Perceived health care availability
was associated with higher likelihood of experiencing unmet health care needs in
both women and men (women = OR: 1.58, 95% CI: 1.09-2.28; men = OR: 1.92, 95% CI:
1.23-2.99). In addition, perceived health care availability was associated with
barrier- and wait times-related unmet health care need among women (OR: 1.83, 95%
CI: 1.13-2.97; OR: 1.93, 95% CI: 1.10-3.40 respectively), and personal choice-
and wait times-related unmet need among men (OR: 1.99, 95% CI: 1.10-3.58).
CONCLUSION: Individuals' perception of health care availability plays a crucial
role in the experience of unmet health care needs, suggesting the importance of
community-based policy development for improving physical conditions and the
social aspect of health care services.
PMID- 28425894
TI - Trends in smoking initiation in Canada: Does non-inclusion of young adults in
tobacco control strategies represent a missed opportunity?
AB - OBJECTIVES: Young adults face high prevalence rates for smoking. Recent evidence
suggests that many people initiate smoking during young adulthood, but little is
currently known about trends in initiation rates for this age group. METHODS: We
examined rates of initiation to first cigarette (FC) and daily smoking (DS)
during youth (5-17 years) and young adulthood (18-25 years) using nationally
representative data from the 2001, 2003, 2005, 2007, 2009, 2011 and 2013 cycles
of the Canadian Community Health Survey. We included all participants aged 25-26
to obtain seven mutually exclusive retrospective cohorts (n = 16 216). We used
logistic regression to examine four correlates of smoking - sex, education,
poverty status, and immigration status - and whether these factors modify time
trends in smoking. RESULTS: We found that initiation rates decreased during youth
(p < 0.001 for FC, p = 0.02 for DS) but not during young adulthood (p = 0.94 for
FC, p = 0.28 for DS). We found that men and respondents with fewer educational
credentials had relatively higher odds of initiating during young adulthood.
Trends in young adulthood stayed constant across subgroups. Trends in youth were
modified by education: participants who did not complete high school had no
decrease in initiation to FC and DS while those with post-secondary education
experienced a decrease in both outcomes. CONCLUSION: Tobacco control has failed
to address smoking initiation during young adulthood. Given the considerable
amount of initiation that occurs during this period, practitioners and policy
makers should direct more of their planning toward young adults.
PMID- 28425895
TI - Understanding sexual orientation and health in Canada: Who are we capturing and
who are we missing using the Statistics Canada sexual orientation question?
AB - OBJECTIVE: Public health research on inequalities in Canada depends heavily on
population data sets such as the Canadian Community Health Survey. While sexual
orientation has three dimensions - identity, behaviour and attraction -
Statistics Canada and public health agencies assess sexual orientation with a
single questionnaire item on identity, defined behaviourally. This study aims to
evaluate this item, to allow for clearer interpretation of sexual orientation
frequencies and inequalities. METHODS: Through an online convenience sampling of
Canadians >=14 years of age, participants (n = 311) completed the Statistics
Canada question and a second set of sexual orientation questions. RESULTS: The
single-item question had an 85.8% sensitivity in capturing sexual minorities,
broadly defined by their sexual identity, lifetime behaviour and attraction.
Kappa statistic for agreement between the single item and sexual identity was
0.89; with past year, lifetime behaviour and attraction were 0.39, 0.48 and 0.57
respectively. The item captured 99.3% of those with a sexual minority identity,
84.2% of those with any lifetime same-sex partners, 98.4% with a past-year same
sex partner, and 97.8% who indicated at least equal attraction to same-sex
persons. CONCLUSION: Findings from Statistics Canada surveys can be best
interpreted as applying to those who identify as sexual minorities. Analyses
using this measure will underidentify those with same-sex partners or attractions
who do not identify as a sexual minority, and should be interpreted accordingly.
To understand patterns of sexual minority health in Canada, there is a need to
incorporate other dimensions of sexual orientation.
PMID- 28425896
TI - A longitudinal cohort study examining determinants of overweight and obesity in
adulthood.
AB - OBJECTIVES: Adulthood overweight and obesity are multifaceted conditions
influenced by a combination of biological, environmental and socio-cultural
factors across the lifespan. Using a longitudinal study design, we aimed to
identify determinants of adulthood overweight and obesity, in relation to: 1)
childhood and life course factors, 2) geographical differences in air quality,
and 3) gender-specific factors, in a cohort followed from childhood into
adulthood. METHODS: Childhood data were acquired (1978-1986) from children
residing in four distinct Hamilton neighbourhoods (Ontario, Canada), including
air-quality assessments. Adulthood data were obtained (2006-2007) from
successfully retraced participants (n = 315) using comprehensive self
administered questionnaires. Multivariate logistic regressions were used to
evaluate determinants of adulthood overweight (BMI: 25-29.9 kg/m2) and obesity
(BMI: >=30). RESULTS: The prevalence of normal weight decreased drastically at
follow-up in adulthood, while that of overweight and obesity increased. Both
overweight and obesity in adulthood were associated with male gender and
occupational exposures to contaminants. Childhood residence in Hamilton
neighbourhoods with better air quality was associated with lesser odds of
adulthood overweight, whereas adulthood obesity was strongly linked to childhood
weight gain (overweight or obesity). Among females, childhood weight status
predicted overweight and obesity in adulthood, with always living in Hamilton,
lack of additional health insurance, negative self-appraisal and high blood
pressure during adulthood identified as other significant predictors. Among
males, prolonged occupational exposures to contaminants emerged as a unique
determinant of adulthood weight gain. CONCLUSION: Adulthood overweight and
obesity are associated with childhood and life course determinants, including
childhood weight status, residential air quality and occupational contaminant
exposures, in a gender-specific manner.
PMID- 28425897
TI - Diabetes among non-obese Filipino Americans: Findings from a large population
based study.
AB - OBJECTIVES: Filipino Americans form the second-largest Asian American and Pacific
Islanders subgroup. Growing evidence suggests that Filipino Americans have higher
rates of diabetes than non-Hispanic whites. The key objectives of this study are
1) to determine the prevalence of diabetes in non-obese Filipino Americans
compared to non-obese non-Hispanic whites, and 2) to identify risk factors for
diabetes in non-obese Filipino men and women. METHODS: Secondary analysis of
population-based data from combined waves (2007, 2009 and 2011) of the adult
California Health Interview Survey (CHIS). The study sample was restricted to non
obese Filipino Americans (n = 1629) and non-Hispanic whites (n = 72 072).
RESULTS: Non-obese Filipino Americans had more than twice the odds of diabetes
compared to non-Hispanic whites, even after correcting for several known risk
factors (OR = 2.80, p < 0.001). For non-obese Filipino men, older age, poverty,
cigarette smoking, and being overweight are associated with increased odds for
diabetes, while older age was the only factor associated with diabetes among
Filipina women. DISCUSSION: Diabetes prevention approaches need to be targeted
towards non-obese Filipino Americans, due to their high risk of diabetes.
PMID- 28425898
TI - Compliance with school nutrition policies in Ontario and Alberta: An assessment
of secondary school vending machine data from the COMPASS study.
AB - OBJECTIVES: We investigated the extent to which a sample of Ontario and Alberta
secondary schools are being compliant with their respective provincial nutrition
policies, in terms of the food and beverages sold in vending machines. METHODS:
This observational study used objective data on drinks and snacks from vending
machines, collected over three years of the COMPASS study (2012/2013-2014/2015
school years). Drink (e.g., sugar-containing carbonated/non-carbonated soft
drinks, sports drinks, etc.) and snack (e.g., chips, crackers, etc.) data were
coded by number of units available, price, and location of vending machine(s) in
the school. Univariate and bivariate analyses were undertaken using R version
3.2.3. In order to assess policy compliancy over time, nutritional information of
products in vending machines was compared to nutrition standards set out in P/PM
150 in Ontario, and those set out in the Alberta Nutrition Guidelines for
Children and Youth (2012) in Alberta. RESULTS: Results reveal a decline over time
in the proportion of schools selling sugar-containing carbonated soft drinks (9%
in 2012/2013 vs. 3% in 2014/2015), crackers (26% vs. 17%) and cake products (12%
vs. 5%) in vending machines, and inconsistent changes in the proportion selling
chips (53%, 67% and 65% over the three school years). Conversely, results
highlight increases in the proportion of vending machines selling chocolate bars
(7% vs. 13%) and cookies (21% vs. 40%) between the 2012/2013 and 2014/2015 school
years. CONCLUSION: Nutritional standard policies were not adhered to in the
majority of schools with respect to vending machines. There is a need for
investment in formal monitoring and evaluation of school policies, and the
provision of information and tools to support nutrition policy implementation.
PMID- 28425899
TI - Associations between the local food environment and the severity of food
insecurity among new families using community food security interventions in
Montreal.
AB - OBJECTIVES: To examine the association between the local food environment and the
severity of food insecurity among new families using community food security
interventions in Montreal. METHODS: In this cross-sectional study, we analyzed
baseline data from 785 adults aged 18-65 years enrolled in the evaluation of the
effects of organizations delivering community food security interventions in
Montreal. The dependent variable was household food insecurity, while the
independent variable was the local food environment, assessed through: location
of the most frequently used grocery store, distance between the participant's
residence and the community organization used, mode of transportation, walking
time to the most frequently used grocery store, satisfaction with the
acceptability and affordability of food available at the most frequently used
grocery store, and self-reported difficulties in accessing food. We used
polytomous logistic regression to estimate the association between household food
insecurity and the local food environment. In all the models, we coded food
security status in three categories: food security, moderate food insecurity and
severe food insecurity. The last group was used as a reference group. RESULTS:
Our data suggest that compared to households with severe food insecurity, those
with moderate food insecurity (OR = 0.43, 95% CI: 0.28-0.62) and those with food
security (OR = 0.13, 95% CI: 0.06-0.26) were less likely to report difficulties
in accessing food due to food affordability. Food-secure households also had
lower odds of reporting difficulties in accessing food due to transportation
constraints (OR = 0.18, 95% CI: 0.06-0.55) compared with severe food-insecure
households. Living a distance of between 1 and 2 km from the organization used
was significantly correlated with moderate food insecurity (OR = 1.80, 95% CI:
1.12-2.88). CONCLUSION: The local food environment is associated with severity of
household food insecurity among new families using community food security
interventions in Montreal. Future studies should study the relationship between
the local food environment and food insecurity across all dimensions of food
access.
PMID- 28425900
TI - ?
AB - OBJECTIFS: Cette etude vise a decrire la mobilisation des representations
ethnoculturelles par des agents et des gestionnaires de sante pour expliquer
l'echec partiel d'une politique de sante maternelle et discuter des consequences
potentielles de ces representations sur l'acces aux soins de sante des
populations.METHODES : Il s'agit d'une recherche qualitative de type socio
anthropologique mobilisant des entretiens approfondis, des discussions
informelles, des observations non participantes menees dans les centres de sante
et une analyse documentaire. Les entretiens ont ete menes aupres de 16 agents de
sante et de 10 gestionnaires. Les entretiens ont ete enregistres sous support
numerique et transcrits. L'etude s'est deroulee dans le district sanitaire de
Djibo au Burkina Faso.RESULTATS : L'identification ethnique, les coutumes
relatives a l'accouchement (pudeur, discretion, presence feminine), le statut
social des femmes (le faible pouvoir decisionnel), le nomadisme et l'organisation
sociale des populations et leurs resistances au changement sont eriges comme des
obstacles " culturels " a la politique de sante. L'usage largement repandu de ces
representations par les agents et les gestionnaires de sante contribue a
reprimander les populations et a masquer les facteurs structurels qui ont
pourtant une influence plus importante sur l'utilisation des services de sante
maternelle. CONCLUSION: Cette recherche met en lumiere le danger de l'usage
excessif des representations ethnoculturelles teintees de culturalisme dans les
pratiques et les politiques de sante publique en vehiculant des stereotypes a
l'egard de certains groupes de population. Pour comprendre le succes ou l'echec
des politiques sanitaires, il demeure important de considerer la qualite du
contact avec le systeme de sante, les facteurs structurels notamment les
capacites des menages a faire face aux depenses des soins de sante et des
distances entre les villages et les centres de sante. Ces elements permettraient
de mieux comprendre les disparites constatees a l'egard des indicateurs
d'utilisation des services de sante.
PMID- 28425901
TI - A systematic review and meta-analysis for the adverse effects, immunogenicity and
efficacy of Lyme disease vaccines: Guiding novel vaccine development.
AB - BACKGROUND: Lyme borreliosis (LB) is the most prevalent arthropod-borne
infectious disease in North America. Currently, no vaccine is available to
prevent LB in humans, although monovalent and multivalent vaccines have been
developed in the past. OBJECTIVE: The aim of the current study is to conduct a
systematic review and meta-analysis to evaluate and compare the findings from
these two classes of vaccines for their reactogenicity, immunogenicity and
efficacy, in the hope this may assist in the development of future vaccines.
METHODS: A search strategy was developed for online databases (PubMed, Ovid
MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme
disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical
trials were included to compare the results of the monovalent vaccines to those
of the multivalent one. Meta-analyses were conducted to evaluate the
reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for
LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the
monovalent vaccine from three different clinical trials at different dose
schedules. RESULTS: Incidence of redness (local adverse effect) and fever
(systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower
(p < 0.05) in individuals who received multivalent vaccines compared to those
receiving the monovalent one. Incidences of all other local and systemic adverse
effects were non-significantly lower in the multivalent vaccine compared to the
monovalent vaccines. Seroprotection was comparable among individuals who received
the two vaccine classes at the 30 MUg dose level. Efficacy in the prevention of
LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95%
CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for
the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26
0.63, p < 0.001). CONCLUSION: The current study further validates that the
monovalent and multivalent LB vaccines result in mild local side effects and self
limiting systemic adverse effects, with the multivalent vaccine slightly more
tolerable than the monovalent one. Both vaccine classes were similarly highly
immunogenic. A new vaccine with high safety standards, better efficacy, low cost,
and public acceptance is yet to be developed. Meanwhile, personal protection
limiting exposure to ticks is recommended.
PMID- 28425902
TI - Evidence for the benefits of food chain interventions on E. coli 0157:H7/NM
prevalence in retail ground beef and human disease incidence: A success story.
AB - OBJECTIVES: Human infection with Escherichia coli O157:H7/NM has historically
been associated with consumption of undercooked ground beef. The purpose of this
paper is to investigate the correlation of the decline in E. coli O157:H7/NM
infections in Canada with the introduction of control efforts in ground beef by
industry. METHODS: The human incidence of E. coli O157:H7/NM, prevalence in
ground beef and interventions from 1996 to 2014 were analyzed. Pathogen
prevalence data were obtained from federal government and industry surveillance
and inspection/compliance programs. A survey of the largest ground beef producers
in Canada was conducted to identify when interventions were implemented. RESULTS:
The incidence of E. coli O157:H7/NM infections in Canada declined from ~4
cases/100 000 to ~1 case/100 000 from 2000 to 2010. Verotoxigenic Escherichia
coli (VTEC) prevalence in ground beef sold at retail declined from about 30%
around the year 2000 to <2% since 2012. Other measures of the prevalence of E.
coli, VTEC, and E. coli O157:H7/NM in beef and ground beef also declined. The
number and types of interventions implemented in the major beef processing
establishments in Canada increased from 1996 to 2016. CONCLUSION: The observed
decline in human illnesses and pathogen levels in relation to retail meats was
associated with the introduction of control efforts by industry, federal and
provincial/territorial governments, and the general population. Industry-led
changes in beef processing along with the introduction of food safety policies,
regulations, and public education have led to improved food safety in Canada.
PMID- 28425903
TI - Improving linkage to HIV care at low-threshold STI/HIV testing sites: An
evaluation of the Immediate Staging Pilot Project in Vancouver, British Columbia.
AB - OBJECTIVES: The objective of the Immediate Staging Pilot Project (ISPP) was to
improve linkage to human immunodeficiency virus (HIV) care by increasing the
number of referrals made to HIV care, and to decrease the time between diagnosis
and linkage to care for newly diagnosed HIV clients. This pilot had the potential
to decrease HIV transmission at a population level by engaging clients in
treatment earlier. SETTING: The Bute Street Clinic and Health Initiative for Men
Clinic on Davie in Vancouver, British Columbia are low-threshold public health
facilities providing HIV/STI testing primarily to men who have sex with men
(MSM). INTERVENTION: To improve engagement of MSM in the cascade of HIV care, the
BC Centre for Disease Control implemented a 12-month ISPP in 2012 for clients
newly diagnosed with HIV. The pilot offered CD4 and viral load testing at the
time of diagnosis, implemented improved referral procedures and enhanced nursing
support for clients. OUTCOMES: Comparing linkage to care outcomes between a group
that received the standard of care (SOC) and an intervention group that received
immediate staging, the median linkage to care time decreased from 21.5 to 14.0
days respectively (p = 0.053). The referral rates to HIV care were 56.1% in the
SOC group and 94.1% in the intervention group (p < 0.001). CONCLUSION: Creating
best practices that include offering CD4 and viral load testing at the time of
diagnosis, enhanced nursing support and standardized referral processes has
facilitated an improvement in the quality of HIV services provided to MSM clients
attending low-threshold clinics.
PMID- 28425904
TI - "Testing is Healthy" TimePlay campaign: Evaluation of sexual health promotion
gamification intervention targeting young adults.
AB - OBJECTIVES: The objectives of the study were to 1) describe the implementation of
the "Testing is Healthy" campaign in four locations in British Columbia (BC) and
2) report process evaluation indicators for the campaign. PARTICIPANTS: Young
adults ages 20-29 years, the age group with the highest reported rates of
chlamydia and gonorrhea in BC. SETTINGS: Movie theatres located in Langley,
Burnaby, Coquitlam and Surrey, which are communities served by the Fraser Health
Authority (FHA) in BC. INTERVENTION: The FHA launched the campaign in 2014 and
2015 to bring down the prevalence of sexually transmitted infections (STIs) and
HIV in the region. The campaign used the Cineplex TimePlay platform to engage
moviegoers in answering STI/HIV-related questions, and to connect them to a
clinic finder on the BC Centre for Disease Control Sex Smart Resource (SSR)
website. TimePlay includes elements of gaming, is technology-based, and has been
a successful advertisement platform for consumer products and services. However,
this is the first time it has been used for sexual health promotion. The campaign
was evaluated for 1) reach, based on theatre attendance and TimePlay
participation, and 2) the effectiveness of connecting people to sexual health
information using SSR web analytics. OUTCOMES: In total, the campaign received
548 410 views and 77 149 plays. SSR web analytics showed a significant increase
in unique page views of the Clinic Finder page between the first and the second
campaign. IMPLICATIONS: The campaign reached a large population at a low cost and
was correlated with spikes in the unique page views for the Clinic Finder page.
PMID- 28425905
TI - More than words: Using visual graphics for community-based health research.
AB - With increased attention to knowledge translation and community engagement in the
applied health research field, many researchers aim to find effective ways of
engaging health policy and decision makers and community stakeholders. While
visual graphics such as graphs, charts, figures and photographs are common in
scientific research dissemination, they are less common as a communication tool
in research. In this commentary, I illustrate how and why visual graphics were
created and used to facilitate dialogue and communication throughout all phases
of a community-based health research study with a rural Indigenous community,
advancing community engagement and knowledge utilization of a research study. I
suggest that it is essential that researchers consider the use of visual graphics
to accurately communicate and translate important health research concepts and
content in accessible forms for diverse research stakeholders and target
audiences.
PMID- 28425906
TI - The Canadian dementia challenge: Ensuring optimal care and services for those at
risk or with dementia throughout the country.
AB - In the next 15 years, Canada is predicted to face a doubling in its population
affected by dementia. By 2038, an estimated 1.1 million Canadians will be
experiencing dementia, with unprecedented impact on social, economic and health
landscapes. In September 2015, the Canadian Academy of Health Sciences convened a
Forum, with the specific thematic goals of reviewing progress towards effective
dementia treatment and prevention, improved systems of care, advanced living and
built environments, and impactful technology developments. The orientation of the
Forum was to focus on potential solutions and advances in these areas. These
areas are integral to the goal of a national end-to-end program, where all
affected Canadians can be optimally supported in their communities and receive
quality of care - regardless of where they live or who they are.
PMID- 28425907
TI - Plain packaging policy: Preventing industry innovations.
AB - The pack is a marketing tool for the tobacco industry - its shape, colour, fonts,
descriptors and logos attract and mislead smokers. Health warnings on cigarette
packs serve as a knowledge reminder for smokers to quit smoking. Plain packaging
eliminates brand imagery elements from cigarette packs and has many benefits,
including the reduction of intention to smoke and the denormalization of smoking
behaviour. The tobacco industry has devised pack and product marketing
innovations that thwart the effectiveness of health warnings. Plain packaging
policy needs to address these innovations by restricting their use and preventing
them from undermining health warnings.
PMID- 28425908
TI - Rotavirus vaccine, breastfeeding, and other factors that could affect
susceptibility to gastroenteritis in young children.
PMID- 28425909
TI - Examining child sedentary behaviour in the context of children's current
multimedia environment.
PMID- 28425910
TI - Inclusion of a broader range of sexual orientations to strengthen the validity
and generalizability of findings.
PMID- 28425911
TI - A response to the use of respondent-driven sampling in urban Indigenous
populations.
PMID- 28425912
TI - How spatial release from masking may fail to function in a highly directional
auditory system.
AB - Spatial release from masking (SRM) occurs when spatial separation between a
signal and masker decreases masked thresholds. The mechanically-coupled ears of
Ormia ochracea are specialized for hyperacute directional hearing, but the
possible role of SRM, or whether such specializations exhibit limitations for
sound source segregation, is unknown. We recorded phonotaxis to a cricket song
masked by band-limited noise. With a masker, response thresholds increased and
localization was diverted away from the signal and masker. Increased separation
from 6 degrees to 90 degrees did not decrease response thresholds or improve
localization accuracy, thus SRM does not operate in this range of spatial
separations. Tympanal vibrations and auditory nerve responses reveal that
localization errors were consistent with changes in peripheral coding of signal
location and flies localized towards the ear with better signal detection. Our
results demonstrate that, in a mechanically coupled auditory system,
specialization for directional hearing does not contribute to source segregation.
PMID- 28425913
TI - Loss of Dnmt3a and Dnmt3b does not affect epidermal homeostasis but promotes
squamous transformation through PPAR-gamma.
AB - The DNA methyltransferase Dnmt3a suppresses tumorigenesis in models of leukemia
and lung cancer. Conversely, deregulation of Dnmt3b is thought to generally
promote tumorigenesis. However, the role of Dnmt3a and Dnmt3b in many types of
cancer remains undefined. Here, we show that Dnmt3a and Dnmt3b are dispensable
for homeostasis of the murine epidermis. However, loss of Dnmt3a-but not Dnmt3b
increases the number of carcinogen-induced squamous tumors, without affecting
tumor progression. Only upon combined deletion of Dnmt3a and Dnmt3b, squamous
carcinomas become more aggressive and metastatic. Mechanistically, Dnmt3a
promotes the expression of epidermal differentiation genes by interacting with
their enhancers and inhibits the expression of lipid metabolism genes, including
PPAR-gamma, by directly methylating their promoters. Importantly, inhibition of
PPAR-gamma partially prevents the increase in tumorigenesis upon deletion of
Dnmt3a. Altogether, we demonstrate that Dnmt3a and Dnmt3b protect the epidermis
from tumorigenesis and that squamous carcinomas are sensitive to inhibition of
PPAR-gamma.
PMID- 28425914
TI - Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at
early and late times after infection.
AB - Latent Epstein-Barr virus (EBV) infection is causally linked to several human
cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the
apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1
constitutively activates NFkappaB and is critical for survival of EBV
immortalized B cells. However, during early infection EBV induces rapid B cell
proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought
to define the mechanism of survival in the absence of LMP1/NFkappaB early after
infection. We used BH3 profiling to query mitochondrial regulation of apoptosis
and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL
1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival
mechanisms is unique to virus-infected cells and relies on regulation of MCL-1
mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein.
This study defines a new role for EBNA3A in the suppression of apoptosis with
implications for EBV lymphomagenesis.
PMID- 28425915
TI - Competition between histone and transcription factor binding regulates the onset
of transcription in zebrafish embryos.
AB - Upon fertilization, the genome of animal embryos remains transcriptionally
inactive until the maternal-to-zygotic transition. At this time, the embryo takes
control of its development and transcription begins. How the onset of zygotic
transcription is regulated remains unclear. Here, we show that a dynamic
competition for DNA binding between nucleosome-forming histones and transcription
factors regulates zebrafish genome activation. Taking a quantitative approach, we
found that the concentration of non-DNA-bound core histones sets the time for the
onset of transcription. The reduction in nuclear histone concentration that
coincides with genome activation does not affect nucleosome density on DNA, but
allows transcription factors to compete successfully for DNA binding. In
agreement with this, transcription factor binding is sensitive to histone levels
and the concentration of transcription factors also affects the time of
transcription. Our results demonstrate that the relative levels of histones and
transcription factors regulate the onset of transcription in the embryo.
PMID- 28425916
TI - Combined ALK and MDM2 inhibition increases antitumor activity and overcomes
resistance in human ALK mutant neuroblastoma cell lines and xenograft models.
AB - The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is
limited, highlighting the need to improve their effectiveness in these patients.
To this end, we sought to develop a combination strategy to enhance the antitumor
activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and
xenograft models expressing activated ALK. Herein, we report that combined
inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and
pro-apoptotic proteins. Consequently, this combination treatment synergistically
inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK
amplification or mutations in vitro, and resulted in complete and durable
responses in neuroblastoma xenografts derived from these cells. We further
demonstrate that concurrent inhibition of MDM2 and ALK was able to overcome
ceritinib resistance conferred by MYCN upregulation in vitro and in vivo.
Together, combined inhibition of ALK and MDM2 may provide an effective treatment
for TP53 wild-type neuroblastoma with ALK aberrations.
PMID- 28425918
TI - Rhein and polydimethylsiloxane functionalized carbon/carbon composites as
prosthetic implants for bone repair applications.
AB - A major issue in bone tissue engineering is the selection of biocompatible
materials for implants, to reduce unwanted inflammatory reactions and promote
cell adhesion. Bone tissue growth on suitable biomedical implants can shorten
recovery and hospitalization after surgery. Therefore, a method to improve tissue
implant integration and healing would be of scientific and clinical interest. In
this work, we permeated polydimethylsiloxane (PDMS) into carbon/carbon (C/C)
composites (PDMS-C/C) and then coated it with 4,5-dihydroxyanthraquinone-2
carboxylic acid (rhein) to create rhein-PDMS-C/C to increase its biocompatibility
and reduce the occurrence of inflammatory reactions. We measured in vitro
adhesion and proliferation of MC3T3-E1 cells and bacteria to evaluate the
biocompatibility and antimicrobial properties of C/C, PDMS-C/C, and rhein-PDMS
C/C. In vivo, x-ray and micro-CT evaluation three, six and nine weeks after
surgery revealed that rhein-PDMS-C/C was more effective than PDMS-C/C and C/C
composite in terms of antibacterial activity, cell adhesion and tissue growth.
Compared with C/C and PDMS-C/C, rhein-PDMS-C/C could be suitable for clinical
applications for bone tissue engineering.
PMID- 28425919
TI - Cell behavior of human mesenchymal stromal cells in response to silica/collagen
based xerogels and calcium deficient culture conditions.
AB - Herein, we aim to elucidate osteogenic effects of two silica-based xerogels with
different degrees of bioactivity on human bone-derived mesenchymal stromal cells
by means of scanning electron microscopy, quantitative PCR enhanced osteogenic
effects and the formation of an extracellular matrix which could be ascribed to
the sample with lower bioactivity. Given the high levels of bioactivity, the
cells revealed remarkable sensitivity to extremely low calcium levels of the
media. Therefore, additional experiments were performed to elucidate cell
behavior under calcium deficient conditions. The results refer to capacity of the
bone-derived stromal cells to overcome calcium deficiency even though
proliferation, migration and osteogenic differentiation capabilities were
diminished. One reason for the differences of the cellular response (on tissue
culture plates versus xerogels) to calcium deficiency seems to be the positive
effect of silica. The silica could be detected intracellularly as shown by time
of flight-secondary ion mass spectrometry after cultivation of primary cells for
21 days on the surfaces of the xerogels. Thus, the present findings refer to
different osteogenic differentiation potentials of the xerogels according to the
different degrees of bioactivity, and to the role of silica as a stimulator of
osteogenesis. Finally, the observed pattern of connexin-based hemichannel gating
supports the assumption that connexin 43 is a key factor for calcium-mediated
osteogenesis in bone-derived mesenchymal stromal cells.
PMID- 28425920
TI - Development of a fast Monte Carlo dose calculation system for online adaptive
radiation therapy quality assurance.
AB - Online adaptive radiation therapy (ART) based on real-time magnetic resonance
imaging represents a paradigm-changing treatment scheme. However, conventional
quality assurance (QA) methods based on phantom measurements are not feasible
with the patient on the treatment couch. The purpose of this work is to develop a
fast Monte Carlo system for validating online re-optimized tri-60Co IMRT adaptive
plans with both high accuracy and speed. The Monte Carlo system is based on dose
planning method (DPM) code with further simplification of electron transport and
consideration of external magnetic fields. A vendor-provided head model was
incorporated into the code. Both GPU acceleration and variance reduction were
implemented. Additionally, to facilitate real-time decision support, a C++ GUI
was developed for visualizing 3D dose distributions and performing various
analyses in an online adaptive setting. A thoroughly validated Monte Carlo code
(gPENELOPE) was used to benchmark the new system, named GPU-accelerated DPM with
variance reduction (gDPMvr). The comparison using 15 clinical IMRT plans
demonstrated that gDPMvr typically runs 43 times faster with only 0.5% loss in
accuracy. Moreover, gDPMvr reached 1% local dose uncertainty within 2.3 min on
average, and thus is well-suited for ART QA.
PMID- 28425917
TI - TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to
provide quality control in the antigen presentation pathway.
AB - Recently, we revealed that TAPBPR is a peptide exchange catalyst that is
important for optimal peptide selection by MHC class I molecules. Here, we asked
whether any other co-factors associate with TAPBPR, which would explain its
effect on peptide selection. We identify an interaction between TAPBPR and UDP
glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the
calnexin/calreticulin quality control cycle that is known to regenerate the
Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a
multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR,
in which TAPBPR promotes the association of UGT1 with peptide-receptive MHC class
I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities
the reglucosylation of the glycan on MHC class I molecules, promoting their
recognition by calreticulin. Our results suggest that in addition to being a
peptide editor, TAPBPR improves peptide optimisation by promoting peptide
receptive MHC class I molecules to associate with the peptide-loading complex.
PMID- 28425921
TI - Plasma Micro-RNA Alterations Appear Late in Pancreatic Cancer.
AB - OBJECTIVES: The aim of this research was to study whether plasma microRNAs
(miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing
prediagnostic plasma samples collected before a PC diagnosis. BACKGROUND: PC has
a poor prognosis due to late presenting symptoms and early metastasis.
Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in
a prediagnostic setting. METHODS: We first performed an initial screen using a
panel of 372 miRNAs in a retrospective case-control cohort that included early
stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis
were then measured in an early detection case-control cohort wherein plasma
samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19
9 (Ca 19-9) levels were measured in all samples for comparison. RESULTS: Our
initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15
candidate miRNAs that were differentially expressed in plasma samples at PC
diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which
outperformed Ca 19-9 in receiver-operating characteristics analysis. However,
none of the candidate miRNAs, individually or in combination, were significantly
altered in prediagnostic plasma samples from 67 future PC patients compared with
132 matched controls. In comparison, Ca 19-9 levels were significantly higher in
the cases at <5 years before diagnosis. CONCLUSION: Plasma miRNAs are altered in
PC patients at diagnosis, but the candidate miRNAs found in this study appear
late in the course of the disease and cannot be used for early detection of the
disease.
PMID- 28425922
TI - Detailed Follow-up Study of Pediatric Orofacial Granulomatosis Patients.
AB - OBJECTIVES: Orofacial granulomatosis (OFG) is a chronic inflammatory condition
affecting the orofacial area. Its connection to Crohn disease (CD) is debated.
Our aim was to describe a cohort of pediatric patients with OFG in detail, study
the long-term behavior of OFG, and evaluate factors predicting CD in patients
with OFG. METHODS: We invited patients diagnosed with OFG at 2 university
hospitals, Finland for a follow-up appointment. Patients (n = 29) were examined
by a dentist and an otorhinolaryngologist using a structural schema. Orofacial
findings were also recorded using digital photographing. Patients filled in
questionnaires about general health and special diets. Patients' nutrition was
evaluated from food records. The findings were compared between patients with OFG
only and OFG with CD. RESULTS: Patients with CD had more findings in the
orofacial area (total score for orofacial findings median 11) compared to
patients with OFG only (total score median 7.5). There was no statistically
significant difference in the type of lesions between these groups, except the
upper lip was more often affected in patients with CD (n = 11) than in patients
with OFG only (n = 0). Most of the patients had normal otorhinolaryngological
findings. All patients with elevated anti-Saccharomyces cerevisiae antibody A
levels had CD (n = 6) and they presented with more orofacial findings (total
score) than patients with normal levels of anti-S cerevisiae antibody A (P =
0.0311). CONCLUSIONS: Long-term follow-up of pediatric-onset patients with OFG
shows good prognosis. Patients with OFG do not seem to have
otorhinolaryngological comorbidity. Anti-S cerevisiae antibody A may serve as a
factor to indicate the possible presence of underlying CD in patients with OFG,
but further studies are requested.
PMID- 28425923
TI - Connectivity Restoration in Wireless Sensor Networks via Space Network Coding.
AB - The problem of finding the number and optimal positions of relay nodes for
restoring the network connectivity in partitioned Wireless Sensor Networks (WSNs)
is Non-deterministic Polynomial-time hard (NP-hard) and thus heuristic methods
are preferred to solve it. This paper proposes a novel polynomial time heuristic
algorithm, namely, Relay Placement using Space Network Coding (RPSNC), to solve
this problem, where Space Network Coding, also called Space Information Flow
(SIF), is a new research paradigm that studies network coding in Euclidean space,
in which extra relay nodes can be introduced to reduce the cost of communication.
Unlike contemporary schemes that are often based on Minimum Spanning Tree (MST),
Euclidean Steiner Minimal Tree (ESMT) or a combination of MST with ESMT, RPSNC is
a new min-cost multicast space network coding approach that combines Delaunay
triangulation and non-uniform partitioning techniques for generating a number of
candidate relay nodes, and then linear programming is applied for choosing the
optimal relay nodes and computing their connection links with terminals.
Subsequently, an equilibrium method is used to refine the locations of the
optimal relay nodes, by moving them to balanced positions. RPSNC can adapt to any
density distribution of relay nodes and terminals, as well as any density
distribution of terminals. The performance and complexity of RPSNC are analyzed
and its performance is validated through simulation experiments.
PMID- 28425924
TI - Roles of Copper-Binding Proteins in Breast Cancer.
AB - Copper ions are needed in several steps of cancer progression. However, the
underlying mechanisms, and involved copper-binding proteins, are mainly elusive.
Since most copper ions in the body (in and outside cells) are protein-bound, it
is important to investigate what copper-binding proteins participate and, for
these, how they are loaded with copper by copper transport proteins. Mechanistic
information for how some copper-binding proteins, such as extracellular lysyl
oxidase (LOX), play roles in cancer have been elucidated but there is still much
to learn from a biophysical molecular viewpoint. Here we provide a summary of
copper-binding proteins and discuss ones reported to have roles in cancer. We
specifically focus on how copper-binding proteins such as mediator of cell
motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich
in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects.
Because of the importance of copper for invasion/migration processes, which are
key components of cancer metastasis, further insights into the actions of copper
binding proteins may provide new targets to combat cancer.
PMID- 28425925
TI - Evaluation of the Immunomodulatory Properties of Streptococcus suis and Group B
Streptococcus Capsular Polysaccharides on the Humoral Response.
AB - Streptococcus suis and group B Streptococcus (GBS) are encapsulated streptococci
causing septicemia and meningitis. Antibodies (Abs) against capsular
polysaccharides (CPSs) have a crucial protective role, but the
structure/composition of the CPS, including the presence of sialic acid, may
interfere with the generation of anti-CPS Ab responses. We investigated the
features of the CPS-specific Ab response directed against S. suis serotypes 2 and
14 and GBS serotypes III and V after infection or immunization with purified
native or desialylated CPSs in mice. Whereas S. suis-infected mice developed a
very low/undetectable CPS-specific IgM response, significant anti-CPS IgM titers
were measured in GBS-infected animals (especially for type III GBS). No isotype
switching was detected in S. suis- or GBS-infected mice. While the expression of
sialic acid was essential for the immunogenicity of purified GBS type III CPS,
this sugar was not responsible for the inability of purified S. suis types 2, 14
and GBS type V CPSs to induce a specific Ab response. Thus, other biochemical
criteria unrelated to the presence of sialic acid may be responsible for the
inaptitude of the host immune system to mount an effective response against
certain S. suis and GBS CPS types.
PMID- 28425926
TI - Chemical Source Localization Fusing Concentration Information in the Presence of
Chemical Background Noise.
AB - We present the estimation of a likelihood map for the location of the source of a
chemical plume dispersed under atmospheric turbulence under uniform wind
conditions. The main contribution of this work is to extend previous proposals
based on Bayesian inference with binary detections to the use of concentration
information while at the same time being robust against the presence of
background chemical noise. For that, the algorithm builds a background model with
robust statistics measurements to assess the posterior probability that a given
chemical concentration reading comes from the background or from a source
emitting at a distance with a specific release rate. In addition, our algorithm
allows multiple mobile gas sensors to be used. Ten realistic simulations and ten
real data experiments are used for evaluation purposes. For the simulations, we
have supposed that sensors are mounted on cars which do not have among its main
tasks navigating toward the source. To collect the real dataset, a special arena
with induced wind is built, and an autonomous vehicle equipped with several
sensors, including a photo ionization detector (PID) for sensing chemical
concentration, is used. Simulation results show that our algorithm, provides a
better estimation of the source location even for a low background level that
benefits the performance of binary version. The improvement is clear for the
synthetic data while for real data the estimation is only slightly better,
probably because our exploration arena is not able to provide uniform wind
conditions. Finally, an estimation of the computational cost of the algorithmic
proposal is presented.
PMID- 28425927
TI - Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E
Variants.
AB - Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic
HEV is an important cause of chronic hepatitis in immunocompromised patients. The
rapid identification of novel HEV variants and accumulating sequence information
has prompted significant changes in taxonomy of the family Hepeviridae. This
family includes two genera: Orthohepevirus, which infects terrestrial
vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there
are four species, A-D, with widely differing host range. Orthohepevirus A
contains the HEV variants infecting humans and its significance continues to
expand with new clinical information. We now recognize eight genotypes within
Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates
among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between
humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and
HEV8, which were recently identified in dromedary and Bactrian camels,
respectively. HEV7 is an example of a novel genotype that was found to have
significance to human health shortly after discovery. In this review, we
summarize recent developments in HEV molecular taxonomy, epidemiology and
evolution and describe the discovery of novel camel HEV genotypes as an
illustrative example of the changes in this field.
PMID- 28425929
TI - Contradictions and Promise for End-of-Life Communication among Family and
Friends: Death over Dinner Conversations.
AB - The free, open-access website called "Let's Get Together and Talk about Death",
or Death over Dinner (DoD), provides resources for initiating end-of-life
conversations with family and friends by taking the frightening-talking about
death-and transforming it into the familiar-a conversation over dinner. This
qualitative, descriptive study uses grounded theory and thematic analysis to
answer the following research question: How do friend and family groups
communicate about death and dying in DoD conversations? To answer this question,
52 dinner groups were recruited and conversations were conducted, which consisted
of a facilitator and volunteers. The facilitators were the researchers or
research assistants who allowed dinner participants to control the conversation
and identify topics of interest, and participants were free to share as much or
as little as they wanted. Our analysis revealed that family and friend groups
communicated similarly in that they talked about similar topics and used similar
communication strategies to discuss those topics. Three major themes emerged:
Desire for a good death, which juxtaposed people's perceptions of a "dreaded"
death with those of a "desirable" death; tactics for coping, which consisted of
the subthemes of humour to diffuse tension or deflect discomfort, spiritual
reassurance, and topic avoidance; and topics that elicit fear or uncertainty,
which consisted of the subthemes of organ and whole-body donation, hospice and
palliative care, wills and advance directives. Ultimately, however, participants
felt their experiences were positive and DoD shows promise as a tool for families
to engage in end-of-life conversations.
PMID- 28425928
TI - Porcine Circoviruses and Xenotransplantation.
AB - Allotransplantation and xenotransplantation may be associated with the
transmission of pathogens from the donor to the recipient. Whereas in the case of
allotransplantation the transmitted microorganisms and their pathogenic effect
are well characterized, the possible influence of porcine microorganisms on
humans is mostly unknown. Porcine circoviruses (PCVs) are common in pig breeds
and they belong to porcine microorganisms that still have not been fully
addressed in terms of evaluating the potential risk of xenotransplantation using
pig cells, tissues, and organs. Two types of PCVs are known: porcine circovirus
(PCV) 1 and PCV2. Whereas PCV1 is apathogenic in pigs, PCV2 may induce severe pig
diseases. Although most pigs are subclinically infected, we do not know whether
this infection impairs pig transplant functionality, particularly because PCV2 is
immunosuppressive. In addition, vaccination against PCV2 is able to prevent
diseases, but in most cases not transmission of the virus. Therefore, PCV2 has to
be eliminated to obtain xenotransplants from uninfected healthy animals. Although
there is evidence that PCV2 does not infect-at least immunocompetent-humans,
animals should be screened using sensitive methods to ensure virus elimination by
selection, Cesarean delivery, vaccination, or embryo transfer.
PMID- 28425930
TI - The Peculiar Glycolytic Pathway in Hyperthermophylic Archaea: Understanding Its
Whims by Experimentation In Silico.
AB - Mathematical models are key to systems biology where they typically describe the
topology and dynamics of biological networks, listing biochemical entities and
their relationships with one another. Some (hyper)thermophilic Archaea contain an
enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase
(GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3
phosphoglycerate omitting adenosine 5'-triphosphate (ATP) formation by substrate
level-phosphorylation via phosphoglycerate kinase. In this study we formulate
three hypotheses that could explain functionally why GAPN exists in these
Archaea, and then construct and use mathematical models to test these three
hypotheses. We used kinetic parameters of enzymes of Sulfolobus solfataricus (S.
solfataricus) which is a thermo-acidophilic archaeon that grows optimally between
60 and 90 degrees C and between pH 2 and 4. For comparison, we used a model of
Saccharomyces cerevisiae (S. cerevisiae), an organism that can live at moderate
temperatures. We find that both the first hypothesis, i.e., that the
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plus phosphoglycerate kinase
(PGK) route (the alternative to GAPN) is thermodynamically too much uphill and
the third hypothesis, i.e., that GAPDH plus PGK are required to carry the flux in
the gluconeogenic direction, are correct. The second hypothesis, i.e., that the
GAPDH plus PGK route delivers less than the 1 ATP per pyruvate that is delivered
by the GAPN route, is only correct when GAPDH reaction has a high rate and 1,3
bis-phosphoglycerate (BPG) spontaneously degrades to 3PG at a high rate.
PMID- 28425931
TI - Chocolate Consumption and Risk of Heart Failure: A Meta-Analysis of Prospective
Studies.
AB - Epidemiological studies have shown inconsistent findings on the association
between chocolate consumption and risk of heart failure (HF). We, therefore,
performed a meta-analysis of prospective studies to determine the role of
chocolate intake in the prevention of HF. We searched databases of PubMed, Web of
Science, and Scopus through December 2016 and scrutinized the reference lists of
relevant literatures to identify eligible studies. Study-specific hazard ratios
(HRs) and 95% confidence intervals (CIs) were aggregated using random effect
models. The dose-response relationship between chocolate consumption and incident
HF was also assessed. This meta-analysis is registered with PROSPERO, number
CRD42017054230. Five prospective studies with 106,109 participants were finally
included. Compared to no consumption of chocolate, the pooled HRs (95% CIs) of HF
were 0.86 (0.82-0.91) for low-to-moderate consumption (<7 servings/week) and 0.94
(0.80-1.09) for high consumption (>=7 servings/week). In dose-response meta
analysis, we detected a curve linear relationship between chocolate consumption
and risk of HF (p for nonlinearity = 0.005). Compared with non-consumption, the
HRs (95% CIs) of HF across chocolate consumption levels were 0.92 (0.88-0.97),
0.86 (0.78-0.94), 0.93 (0.85-1.03), and 1.07 (0.92-1.23) for 1, 3, 7, and 10
servings/week, respectively. In conclusion, chocolate consumption in moderation
may be associated with a decreased risk of HF.
PMID- 28425932
TI - Validation of a Novel Technique and Evaluation of the Surface Free Energy of
Food.
AB - Characterizing the physical properties of a surface is largely dependent on
determining the contact angle exhibited by a liquid. Contact angles on the
surfaces of rough and irregularly-shaped food samples are difficult to measure
using a contact angle meter (goniometer). As a consequence, values for the
surface energy and its components can be mismeasured. The aim of this work was to
use a novel contact angle measurement method, namely the snake-based ImageJ
program, to accurately measure the contact angles of rough and irregular shapes,
such as food samples, and so enable more accurate calculation of the surface
energy of food materials. In order to validate the novel technique, the contact
angles of three different test liquids on four different smooth polymer films
were measured using both the ImageJ software with the DropSnake plugin and the
widely used contact angle meter. The distributions of the values obtained by the
two methods were different. Therefore, the contact angles, surface energies, and
polar and dispersive components of plastic films obtained using the ImageJ
program and the Drop Shape Analyzer (DSA) were interpreted with the help of
simple linear regression analysis. As case studies, the superficial
characteristics of strawberry and endive salad epicarp were measured with the
ImageJ program and the results were interpreted with the Drop Shape Analyzer
equivalent according to our regression models. The data indicated that the ImageJ
program can be successfully used for contact angle determination of rough and
strongly hydrophobic surfaces, such as strawberry epicarp. However, for the
special geometry of droplets on slightly hydrophobic surfaces, such as salad
leaves, the program code interpolation part can be altered.
PMID- 28425933
TI - Study on the Rationality for Antiviral Activity of Flos Lonicerae Japonicae
Fructus Forsythiae Herb Chito-Oligosaccharide via Integral Pharmacokinetics.
AB - In the present study, the rationality for the antiviral effect (H1N1 virus) of
Flos Lonicerae Japonicae (FLJ, named JinYinHua)-Fructus forsythiae (FF, named
LianQiao) herb couple preparations improved by chito-oligosaccharide (COS) was
investigated. We found that the improvement of antiviral activity for four
preparations attributed to the enhancement of bioavailability for the FLJ-FF herb
couple in vivo, and that caffeic acid derivatives are the most important type of
components for antiviral activity. The anti-Influenza virus activity-half maximal
inhibitory concentration (IC50), not area under concentration (AUC) was
considered as the weighting factor for integrating the pharmacokinetics of
caffeic acid derivatives. It was found that the integral absorption, both in
vitro and in vivo, especially that in Shuang-Huang-Lian, can be improved
significantly by COS, an absorption enhancer based on tight junction. The results
indicated that the antiviral activity in four preparations improved by COS was
mainly attributed to the integral absorption enhancement of caffeic acid
derivatives.
PMID- 28425934
TI - Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow
Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological
Approaches.
AB - Particulate matter (PM) contains heavy metals that affect various cellular
functions and gene expression associated with a range of acute and chronic
diseases in humans. However, the specific effects they exert on the stem cells
remain unclear. Here, we report the effects of PM collected from the city of
Jeddah on proliferation, cell death, related gene expression and systems of
biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim
of understanding the underlying mechanisms. PM2.5 and PM10 were tested in vitro
at various concentrations (15 to 300 ug/mL) and durations (24 to 72 h). PMs
induced cellular stress including membrane damage, shrinkage and death. Lower
concentrations of PM2.5 increased proliferation of BM-MSCs, while higher
concentrations served to decrease it. PM10 decreased BM-MSCs proliferation in a
concentration-dependent manner. The X-ray fluorescence spectrometric analysis
showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis
(IPA) and hierarchical clustering analyses demonstrated that heavy metals were
associated with signaling pathways involving cell stress/death, cancer and
chronic diseases. qRT-PCR results showed differential expression of the apoptosis
genes (BCL2, BAX); inflammation associated genes (TNF-alpha and IL-6) and the
cell cycle regulation gene (p53). We conclude that PM causes inflammation and
cell death, and thereby predisposes to chronic debilitating diseases.
PMID- 28425935
TI - Water Access, Sanitation, and Hygiene Conditions and Health Outcomes among Two
Settlement Types in Rural Far North Cameroon.
AB - The Far North region in Cameroon has been more heavily impacted by cholera than
any other region over the past decade, but very little has been done to study the
drivers of waterborne diseases in the region. We investigated the relationship
between water, sanitation, and hygiene (WASH) parameters, microbial and
antibiotic resistance (AR) contamination levels in drinking water, and health
outcomes using health survey and molecular analysis during June and July of 2014
in two settlement types (agro-pastoralist villages and transhumant pastoralist
camps). Quantitative polymerase chain reaction was used to determine fecal
contamination sources, enteric pathogens, and antibiotic resistance genes.
Ruminant-associated fecal contamination was widespread in both settlement types
(81.2%), with human-associated contamination detected in 21.7% of the samples.
Salmonella spp. (59.4%) and Shiga toxin-producing E. coli (stx1 44.9% and stx2
31.9%) were detected across all samples. Tetracycline resistance was found only
in village samples. A significant difference in diarrheal incidence within the
past 28 days among young children was found between camps (31.3%) and villages
(0.0%). Our findings suggest that water contamination may play an important role
in contributing to gastrointestinal illness, supporting the need for future
research and public health intervention to reduce gastrointestinal illness in the
area.
PMID- 28425936
TI - Genistein Ameliorates Ischemia/Reperfusion-Induced Renal Injury in a SIRT1
Dependent Manner.
AB - Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation
in clinical practice. Genistein, the main isoflavone found in soy products, is
known to possess a wide spectrum of biochemical and pharmacological activities.
However, the protective effect of genistein on renal I/R injury has not been well
investigated. In the current study, we explore whether genistein exhibits its
renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We
found the treatment of genistein significantly reduced renal I/R-induced cell
death, simultaneously stimulating renal cell proliferation. Meanwhile, SIRT1
expression was up-regulated following the administration of genistein in renal
region. Furthermore, pharmacological inhibition or shRNA-mediated depletion of
SIRT1 significantly reversed the protective effect of genistein on renal
dysfunction, cellular damage, apoptosis, and proliferation following I/R injury,
suggesting an indispensible role of the increased SIRT1 expression and activity
in this process. Meanwhile, the reduced p53 and p21 expression and increased PCNA
(Proliferating Cell Nuclear Antigen) expression were blocked after the depletion
of SIRT1 compared with the genistein treatment group in the renal I/R process.
Hence, our results provided further experimental basis for the potential use of
genistein for the treatment of kidney disease with deficiency of SIRT1 activity.
PMID- 28425937
TI - Gamma-Aminobutyric Acid Increases the Production of Short-Chain Fatty Acids and
Decreases pH Values in Mouse Colon.
AB - Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the
gastrointestinal tract. The present study aimed to investigate the effect of GABA
on colon health in mice. The female Kunming mice were given GABA at doses of 5,
10, 20 and 40 mg/kg/d for 14 days. Afterwards, the short-chain fatty acids
(SCFAs) concentrations, pH values, colon index, colon length and weight of
colonic and cecal contents were determined to evaluate the effects of GABA on
colon health. The results showed that intake of GABA could increase the
concentrations of acetate, propionate, butyrate and total SCFAs in colonic and
cecal contents, as well as the weight of colonic and cecal contents. The colon
index and length of the 40 mg/kg/d GABA-treated group were significantly higher
than those of the control group (p < 0.05). In addition, decrease of pH values in
colonic and cecal contents was also observed. These results suggest that GABA may
improve colon health.
PMID- 28425938
TI - The Sodium Content of Processed Foods in South Africa during the Introduction of
Mandatory Sodium Limits.
AB - BACKGROUND: In June 2016, the Republic of South Africa introduced legislation for
mandatory limits for the upper sodium content permitted in a wide range of
processed foods. We assessed the sodium levels of packaged foods in South Africa
during the one-year period leading up to the mandatory implementation date of the
legislation. METHODS: Data on the nutritional composition of packaged foods was
obtained from nutrition information panels on food labels through both in-store
surveys and crowdsourcing by users of the HealthyFood Switch mobile phone app
between June 2015 and August 2016. Summary sodium levels were calculated for 15
food categories, including the 13 categories covered by the sodium legislation.
The percentage of foods that met the government's 2016 sodium limits was also
calculated. RESULTS: 11,065 processed food items were included in the analyses;
1851 of these were subject to the sodium legislation. Overall, 67% of targeted
foods had a sodium level at or below the legislated limit. Categories with the
lowest percentage of foods that met legislated limits were bread (27%), potato
crisps (41%), salt and vinegar flavoured snacks (42%), and raw processed sausages
(45%). About half (49%) of targeted foods not meeting the legislated limits were
less than 25% above the maximum sodium level. CONCLUSION: Sodium levels in two
thirds of foods covered by the South African sodium legislation were at or below
the permitted upper levels at the mandatory implementation date of the
legislation and many more were close to the limit. The South African food
industry has an excellent opportunity to rapidly meet the legislated
requirements.
PMID- 28425941
TI - Response to Comments by Vuksan V. et al., Nutrients 2017, 9, 398, Regarding an
Article by Solah V.A. et al., Nutrients 2017, 9, 149.
AB - n/a.
PMID- 28425940
TI - Circadian Clock, Cell Division, and Cancer: From Molecules to Organism.
AB - As a response to environmental changes driven by the Earth's axial rotation, most
organisms evolved an internal biological timer-the so called circadian clock
which regulates physiology and behavior in a rhythmic fashion. Emerging evidence
suggests an intimate interplay between the circadian clock and another
fundamental rhythmic process, the cell cycle. However, the precise mechanisms of
this connection are not fully understood. Disruption of circadian rhythms has a
profound impact on cell division and cancer development and, vice versa,
malignant transformation causes disturbances of the circadian clock. Conventional
knowledge attributes tumor suppressor properties to the circadian clock. However,
this implication might be context-dependent, since, under certain conditions, the
clock can also promote tumorigenesis. Therefore, a better understanding of the
molecular links regulating the physiological balance between the two cycles will
have potential significance for the treatment of cancer and associated disorders.
PMID- 28425942
TI - Seasonal Dynamics of Haptophytes and dsDNA Algal Viruses Suggest Complex Virus
Host Relationship.
AB - Viruses influence the ecology and diversity of phytoplankton in the ocean. Most
studies of phytoplankton host-virus interactions have focused on bloom-forming
species like Emiliania huxleyi or Phaeocystis spp. The role of viruses infecting
phytoplankton that do not form conspicuous blooms have received less attention.
Here we explore the dynamics of phytoplankton and algal viruses over several
sequential seasons, with a focus on the ubiquitous and diverse phytoplankton
division Haptophyta, and their double-stranded DNA viruses, potentially with the
capacity to infect the haptophytes. Viral and phytoplankton abundance and
diversity showed recurrent seasonal changes, mainly explained by hydrographic
conditions. By 454 tag-sequencing we revealed 93 unique haptophyte operational
taxonomic units (OTUs), with seasonal changes in abundance. Sixty-one unique
viral OTUs, representing Megaviridae and Phycodnaviridae, showed only distant
relationship with currently isolated algal viruses. Haptophyte and virus
community composition and diversity varied substantially throughout the year, but
in an uncoordinated manner. A minority of the viral OTUs were highly abundant at
specific time-points, indicating a boom-bust relationship with their host. Most
of the viral OTUs were very persistent, which may represent viruses that coexist
with their hosts, or able to exploit several host species.
PMID- 28425939
TI - Fructose Consumption in the Development of Obesity and the Effects of Different
Protocols of Physical Exercise on the Hepatic Metabolism.
AB - Fructose consumption has been growing exponentially and, concomitant with this,
the increase in the incidence of obesity and associated complications has
followed the same behavior. Studies indicate that fructose may be a carbohydrate
with greater obesogenic potential than other sugars. In this context, the liver
seems to be a key organ for understanding the deleterious health effects promoted
by fructose consumption. Fructose promotes complications in glucose metabolism,
accumulation of triacylglycerol in the hepatocytes, and alterations in the lipid
profile, which, associated with an inflammatory response and alterations in the
redox state, will imply a systemic picture of insulin resistance. However,
physical exercise has been indicated for the treatment of several chronic
diseases. In this review, we show how each exercise protocol (aerobic, strength,
or a combination of both) promote improvements in the obesogenic state created by
fructose consumption as an improvement in the serum and liver lipid profile (high
density lipoprotein (HDL) increase and decrease triglyceride (TG) and low-density
lipoprotein (LDL) levels) and a reduction of markers of inflammation caused by an
excess of fructose. Therefore, it is concluded that the practice of aerobic
physical exercise, strength training, or a combination of both is essential for
attenuating the complications developed by the consumption of fructose.
PMID- 28425944
TI - Erratum: Effect of Fibre Supplementation on Body Weight and Composition,
Frequency of Eating and Dietary Choice in Overweight Individuals Nutrients 2017,
9, 149.
AB - n/a.
PMID- 28425943
TI - Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a
High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers.
AB - Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders
exhibited by two major phenotypic forms: Crohn's disease and ulcerative colitis.
Although the aetiology of IBD is unknown, several factors coming from the adipose
tissue and skeletal muscles, such as cytokines, adipokines and myokines, were
suggested in the pathogenesis of ulcerative colitis; however, it has not been
extensively studied whether voluntary exercise can ameliorate that disorder. We
explored the effect of moderate exercise (i.e., voluntary wheel running) on the
disease activity index (DAI), colonic blood flow (CBF), plasma irisin and
adiponectin levels and real-time PCR expression of proinflammatory markers in
mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed
a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic
and microscopic colitis in sedentary SD mice was accompanied by a significant
fall in CBF, some increase in colonic tissue weight and a significant increase in
the plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6, monocyte
chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice,
colonic lesions were aggravated, colonic tissue weight increased and the plasma
TNF-alpha, IL-6, MCP-1, IL-1beta and leptin levels significantly increased.
Simultaneously, a significant decrease in the plasma irisin and adiponectin
levels was observed in comparison with SD mice (p < 0.05). Exercise significantly
decreased macroscopic and microscopic colitis, substantially increased CBF and
attenuated the plasma TNF-alpha, IL-6, MCP-1, IL-1beta and leptin levels while
raising the plasma irisin and the plasma and WAT concentrations of adiponectin in
HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in
HFD mice, possibly due to a fall in colonic microcirculation and an increase in
the plasma and mesenteric fat content of proinflammatory biomarkers; and (2)
voluntary physical activity can attenuate the severity of colonic damage in mice
fed a HFD through the release of protective irisin and restoration of plasma
adiponectin.
PMID- 28425945
TI - A Systematic Review: Costing and Financing of Water, Sanitation, and Hygiene
(WASH) in Schools.
AB - Despite the success of recent efforts to increase access to improved water,
sanitation, and hygiene (WASH) globally, approximately one-third of schools
around the world still lack adequate WASH services. A lack of WASH in schools can
lead to the spread of preventable disease and increase school absences,
especially among women. Inadequate financing and budgeting has been named as a
key barrier for integrating successful and sustainable WASH programs into school
settings. For this reason, the purpose of this review is to describe the current
knowledge around the costs of WASH components as well as financing models that
could be applied to WASH in schools. Results show a lack of information around
WASH costing, particularly around software elements as well as a lack of data
overall for WASH in school settings as compared to community WASH. This review
also identifies several key considerations when designing WASH budgets or
selecting financing mechanisms. Findings may be used to advise future WASH in
school programs.
PMID- 28425946
TI - Robot-Beacon Distributed Range-Only SLAM for Resource-Constrained Operation.
AB - This work deals with robot-sensor network cooperation where sensor nodes
(beacons) are used as landmarks for Range-Only (RO) Simultaneous Localization and
Mapping (SLAM). Most existing RO-SLAM techniques consider beacons as passive
devices disregarding the sensing, computational and communication capabilities
with which they are actually endowed. SLAM is a resource-demanding task. Besides
the technological constraints of the robot and beacons, many applications impose
further resource consumption limitations. This paper presents a scalable
distributed RO-SLAM scheme for resource-constrained operation. It is capable of
exploiting robot-beacon cooperation in order to improve SLAM accuracy while
meeting a given resource consumption bound expressed as the maximum number of
measurements that are integrated in SLAM per iteration. The proposed scheme
combines a Sparse Extended Information Filter (SEIF) SLAM method, in which each
beacon gathers and integrates robot-beacon and inter-beacon measurements, and a
distributed information-driven measurement allocation tool that dynamically
selects the measurements that are integrated in SLAM, balancing uncertainty
improvement and resource consumption. The scheme adopts a robot-beacon
distributed approach in which each beacon participates in the selection,
gathering and integration in SLAM of robot-beacon and inter-beacon measurements,
resulting in significant estimation accuracies, resource-consumption efficiency
and scalability. It has been integrated in an octorotor Unmanned Aerial System
(UAS) and evaluated in 3D SLAM outdoor experiments. The experimental results
obtained show its performance and robustness and evidence its advantages over
existing methods.
PMID- 28425947
TI - Deep Count: Fruit Counting Based on Deep Simulated Learning.
AB - Recent years have witnessed significant advancement in computer vision research
based on deep learning. Success of these tasks largely depends on the
availability of a large amount of training samples. Labeling the training samples
is an expensive process. In this paper, we present a simulated deep convolutional
neural network for yield estimation. Knowing the exact number of fruits, flowers,
and trees helps farmers to make better decisions on cultivation practices, plant
disease prevention, and the size of harvest labor force. The current practice of
yield estimation based on the manual counting of fruits or flowers by workers is
a very time consuming and expensive process and it is not practical for big
fields. Automatic yield estimation based on robotic agriculture provides a viable
solution in this regard. Our network is trained entirely on synthetic data and
tested on real data. To capture features on multiple scales, we used a modified
version of the Inception-ResNet architecture. Our algorithm counts efficiently
even if fruits are under shadow, occluded by foliage, branches, or if there is
some degree of overlap amongst fruits. Experimental results show a 91% average
test accuracy on real images and 93% on synthetic images.
PMID- 28425949
TI - An Efficient Distributed Compressed Sensing Algorithm for Decentralized Sensor
Network.
AB - We consider the joint sparsity Model 1 (JSM-1) in a decentralized scenario, where
a number of sensors are connected through a network and there is no fusion
center. A novel algorithm, named distributed compact sensing matrix pursuit
(DCSMP), is proposed to exploit the computational and communication capabilities
of the sensor nodes. In contrast to the conventional distributed compressed
sensing algorithms adopting a random sensing matrix, the proposed algorithm
focuses on the deterministic sensing matrices built directly on the real
acquisition systems. The proposed DCSMP algorithm can be divided into two
independent parts, the common and innovation support set estimation processes.
The goal of the common support set estimation process is to obtain an estimated
common support set by fusing the candidate support set information from an
individual node and its neighboring nodes. In the following innovation support
set estimation process, the measurement vector is projected into a subspace that
is perpendicular to the subspace spanned by the columns indexed by the estimated
common support set, to remove the impact of the estimated common support set. We
can then search the innovation support set using an orthogonal matching pursuit
(OMP) algorithm based on the projected measurement vector and projected sensing
matrix. In the proposed DCSMP algorithm, the process of estimating the common
component/support set is decoupled with that of estimating the innovation
component/support set. Thus, the inaccurately estimated common support set will
have no impact on estimating the innovation support set. It is proven that under
the condition the estimated common support set contains the true common support
set, the proposed algorithm can find the true innovation set correctly. Moreover,
since the innovation support set estimation process is independent of the common
support set estimation process, there is no requirement for the cardinality of
both sets; thus, the proposed DCSMP algorithm is capable of tackling the unknown
sparsity problem successfully.
PMID- 28425948
TI - Characterization of N-Acyl Homoserine Lactones in Vibrio tasmaniensis LGP32 by a
Biosensor-Based UHPLC-HRMS/MS Method.
AB - Since the discovery of quorum sensing (QS) in the 1970s, many studies have
demonstrated that Vibrio species coordinate activities such as biofilm formation,
virulence, pathogenesis, and bioluminescence, through a large group of molecules
called N-acyl homoserine lactones (AHLs). However, despite the extensive
knowledge on the involved molecules and the biological processes controlled by QS
in a few selected Vibrio strains, less is known about the overall diversity of
AHLs produced by a broader range of environmental strains. To investigate the
prevalence of QS capability of Vibrio environmental strains we analyzed 87 Vibrio
spp. strains from the Banyuls Bacterial Culture Collection (WDCM911) for their
ability to produce AHLs. This screening was based on three biosensors, which
cover a large spectrum of AHLs, and revealed that only 9% of the screened
isolates produced AHLs in the defined experimental conditions. Among these AHL
producing strains, Vibrio tasmaniensis LGP32 is a well-known pathogen of
bivalves. We further analyzed the diversity of AHLs produced by this strain using
a sensitive bioguided UHPLC-HRMS/MS approach (Ultra-High-Performance Liquid
Chromatography followed by High-Resolution tandem Mass Spectrometry) and we
identified C10-HSL, OH-C12-HSL, oxo-C12-HSL and C14:1-HSL as QS molecules. This
is the first report that documents the production of AHL by Vibrio tasmaniensis
LGP32.
PMID- 28425950
TI - Diversity Analysis and Bioresource Characterization of Halophilic Bacteria
Isolated from a South African Saltpan.
AB - Though intensive research has been channeled towards the biotechnological
applications of halophiles and other extremophilic microbes, these studies have
not been, by any means, exhaustive. Saline environments still offer a vast
diversity of microbes with potential to produce an array of natural products
which can only be unlocked by concerted research efforts. In this study, a
combination of culture and molecular approaches were employed to characterize
halophilic bacteria from saltpan water samples and profile their potential
biotechnological applications. Physicochemical analysis of the water samples
showed that pH was alkaline (pH 8.8), with a salinity of 12.8%. 16S rRNA gene
targeted amplicon analysis produced 10 bacterial phyla constituting of
Bacteroidetes (30.57%), Proteobacteria (15.27%), Actinobacteria (9.05%),
Planctomycetes (5.52%) and Cyanobacteria (3.18%). Eighteen strains were
identified using sequencing analysis of the culturable bacterial strains. From
these, the strains SP7 and SP9 were positive for cellulase production while the
strains SP4, SP8 and SP22 were positive for lipase production. Quantitative
enzyme assays showed moderate extracellular cellulase activity (1.95 U/mL) and
lipase activity (3.71 U/mL) by the isolate SP9 and SP4 respectively. Further, of
the six isolates, the isolate SP9 exhibited exploitable potential in the
bioremediation of hydrocarbon pollution as demonstrated by its fairly high
activity against benzanthracene (70% DCPIP reduction). Elucidation of the
isolates secondary metabolites showed the production of the molecules 2,3
butanediol, hexahydro-3-(2-methylpropyl)pyrrole[1,2a]pyrazine-1,4-dione,
aziridine, dimethylamine and ethyl acetate (GC-MS) and oxypurinol and 5
hydroxydecanoic acid (LC-MS), particularly by the isolate Salinivibrio sp. SP9.
Overall, the study showed that the isolated halophiles can produce secondary
metabolites with potential industrial and pharmaceutical application.
PMID- 28425951
TI - Modification of Natural Eudesmane Scaffolds via Mizoroki-Heck Reactions.
AB - The Mizoroki-Heck reaction was applied to substrates derived from isocostic and
ilicic acids, important sesquiterpene components of Dittrichia viscosa L. Greuter
that were extracted directly from plant material collected in Morocco. After
optimization of the metallo-catalysis conditions, various aryl-groups were
successfully introduced on the exocyclic double bond with an exclusive E
configuration and without racemization.
PMID- 28425953
TI - Cancer Chemotherapy Specific to Acidic Nests.
AB - The realization of cancer therapeutics specific to cancer cells with less of an
effect on normal tissues is our goal. Many trials have been carried out for this
purpose, but this goal is still far from being realized. It was found more than
80 years ago that solid cancer nests are acidified, but in vitro studies under
acidic conditions have not been extensively studied. Recently, in vitro
experiments under acidic conditions were started and anti-cancer drugs specific
to acidic areas have been identified. Many genes have been reported to be
expressed at a high level under acidic conditions, and such genes may be potent
targets for anti-cancer drugs specific to acidic nests. In this review article,
recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with
marked efficacy under acidic conditions are summarized, and the clinical use of
anti-cancer drugs specific to acidic nests is discussed.
PMID- 28425952
TI - Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory
Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived
Neurotrophic Factor Levels-An Ex Vivo Study.
AB - Metformin, the popular anti-diabetic drug was shown to exert multiple biological
effects. The most recent metformin gained attention as an agent that mobilizes
endogenous progenitor cells and enhances regenerative potential of organisms, for
example by promoting neurogenesis. In the present study, we examined the role of
metformin on mouse olfactory ensheathing cells (mOECs) derived from animals
receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The
mOECs expanded ex vivo were characterized in terms of their cellular phenotype,
morphology, proliferative activity, viability and accumulation of oxidative
stress factors. Moreover, we determined the mRNA and protein levels of brain
derived neurotrophic factor (BDNF), distinguishing the secretion of BDNF by mOECs
in cultures and circulating serum levels of BDNF. The mOECs used in the
experiment were glial fibrillary acidic protein (GFAP) and p75 neurotrophin
receptor (p75NTR) positive and exhibited both astrocyte-like and non-myelin
Schwann cell-like morphologies. Our results revealed that the proliferation of
OECs derived from mice treated with metformin was lowered, when compared to
control group. Simultaneously, we noted increased cell viability, reduced
expression of markers associated with cellular senescence and a decreased amount
of reactive oxygen species. We observed increased mRNA expression of BDNF and its
down-stream genes. Obtained results indicate that metformin may exert
antioxidant, anti-apoptotic and senolytic action on OECs expanded ex vivo.
PMID- 28425955
TI - Homomorphic Filtering for Improving Time Synchronization in Wireless Networks.
AB - Wireless sensor networks are used to sample the environment in a distributed way.
Therefore, it is mandatory for all of the measurements to be tightly synchronized
in order to guarantee that every sensor is sampling the environment at the exact
same instant of time. The synchronization drift gets bigger in environments
suffering from temperature variations. Thus, this work is focused on improving
time synchronization under deployments with temperature variations. The working
hypothesis demonstrated in this work is that the clock skew of two nodes (the
ratio of the real frequencies of the oscillators) is composed of a multiplicative
combination of two main components: the clock skew due to the variations between
the cut of the crystal of each oscillator and the clock skew due to the different
temperatures affecting the nodes. By applying a nonlinear filtering, the
homomorphic filtering, both components are separated in an effective way. A
correction factor based on temperature, which can be applied to any
synchronization protocol, is proposed. For testing it, an improvement of the FTSP
synchronization protocol has been developed and physically tested under
temperature variation scenarios using TelosB motes flashed with the IEEE 802.15.4
implementation supplied by TinyOS.
PMID- 28425954
TI - Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition.
AB - The etiology and pathophysiology of type 1 diabetes remain largely elusive with
no established concepts for a causal therapy. Efforts to clarify genetic
susceptibility and screening for environmental factors have identified the
vitamin D system as a contributory pathway that is potentially correctable. This
review aims at compiling all genetic studies addressing the vitamin D system in
type 1 diabetes. Herein, association studies with case control cohorts are
presented as well as family investigations with transmission tests, meta-analyses
and intervention trials. Additionally, rare examples of inborn errors of vitamin
D metabolism manifesting with type 1 diabetes and their immune status are
discussed. We find a majority of association studies confirming a predisposing
role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D
metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D
activation. Associations, however, are tenuous in relation to the ethnic
background of the studied populations. Intervention trials identify the specific
requirements of adequate vitamin D doses to achieve vitamin D sufficiency.
Preliminary evidence suggests that doses may need to be individualized in order
to achieve target effects due to pharmacogenomic variation.
PMID- 28425956
TI - Acceptable Risk Analysis for Abrupt Environmental Pollution Accidents in
Zhangjiakou City, China.
AB - Abrupt environmental pollution accidents cause considerable damage worldwide to
the ecological environment, human health, and property. The concept of acceptable
risk aims to answer whether or not a given environmental pollution risk exceeds a
societally determined criterion. This paper presents a case study on acceptable
environmental pollution risk conducted through a questionnaire survey carried out
between August and October 2014 in five representative districts and two counties
of Zhangjiakou City, Hebei Province, China. Here, environmental risk primarily
arises from accidental water pollution, accidental air pollution, and tailings
dam failure. Based on 870 valid questionnaires, demographic and regional
differences in public attitudes towards abrupt environmental pollution risks were
analyzed, and risk acceptance impact factors determined. The results showed
females, people between 21-40 years of age, people with higher levels of
education, public servants, and people with higher income had lower risk
tolerance. People with lower perceived risk, low-level risk knowledge, high-level
familiarity and satisfaction with environmental management, and without
experience of environmental accidents had higher risk tolerance. Multiple
logistic regression analysis indicated that public satisfaction with
environmental management was the most significant factor in risk acceptance,
followed by perceived risk of abrupt air pollution, occupation, perceived risk of
tailings dam failure, and sex. These findings should be helpful to local decision
makers concerned with environmental risk management (e.g., selecting target
groups for effective risk communication) in the context of abrupt environmental
accidents.
PMID- 28425957
TI - Investigating Surface and Near-Surface Bushfire Fuel Attributes: A Comparison
between Visual Assessments and Image-Based Point Clouds.
AB - Visual assessment, following guides such as the Overall Fuel Hazard Assessment
Guide (OFHAG), is a common approach for assessing the structure and hazard of
varying bushfire fuel layers. Visual assessments can be vulnerable to imprecision
due to subjectivity between assessors, while emerging techniques such as image
based point clouds can offer land managers potentially more repeatable
descriptions of fuel structure. This study compared the variability of estimates
of surface and near-surface fuel attributes generated by eight assessment teams
using the OFHAG and Fuels3D, a smartphone method utilising image-based point
clouds, within three assessment plots in an Australian lowland forest. Surface
fuel hazard scores derived from underpinning attributes were also assessed.
Overall, this study found considerable variability between teams on most visually
assessed variables, resulting in inconsistent hazard scores. Variability was
observed within point cloud estimates but was, however, on average two to eight
times less than that seen in visual estimates, indicating greater consistency and
repeatability of this method. It is proposed that while variability within the
Fuels3D method may be overcome through improved methods and equipment,
inconsistencies in the OFHAG are likely due to the inherent subjectivity between
assessors, which may be more difficult to overcome. This study demonstrates the
capability of the Fuels3D method to efficiently and consistently collect data on
fuel hazard and structure, and, as such, this method shows potential for use in
fire management practices where accurate and reliable data is essential.
PMID- 28425958
TI - Reactions of 5-Indolizyl Lithium Compounds with Some Bielectrophiles.
AB - Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides
giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl
pyruvate giving 1,2-hydroxyacid. However, with alpha-halocarbonyl compounds, they
react in different ways, forming the products of selective bromination at C-5
(with alpha-bromo ketones and esters of alpha-bromo acids) and 5-chloroacetyl
indolizines.
PMID- 28425959
TI - The Cost of Arbovirus Disease Prevention in Europe: Area-Wide Integrated Control
of Tiger Mosquito, Aedes albopictus, in Emilia-Romagna, Northern Italy.
AB - Aedes albopictus (tiger mosquito) has become the most invasive mosquito species
worldwide, in addition to being a well-known vector of diseases, with a proven
capacity for the transmission of chikungunya and dengue viruses in Europe as well
as the Zika virus in Africa and in laboratory settings. This research quantifies
the cost that needs to be provided by public-health systems for area-wide
prevention of arboviruses in Europe. This cost has been calculated by evaluating
the expenditure of the plan for Aedes albopictus control set up in the Emilia
Romagna region (Northern Italy) after a chikungunya outbreak occurred in 2007.
This plan involves more than 280 municipalities with a total of 4.2 million
inhabitants. Public expenditure for plan implementation in 2008-2011 was examined
through simple descriptive statistics. Annual expenditure was calculated to be
approximately ?1.3 per inhabitant, with a declining trend (from a total of ?7.6
million to ?5.3 million) and a significant variability at the municipality level.
The preventative measures in the plan included antilarval treatments (about 75%
of total expenditure), education for citizens and in schools, entomological
surveillance, and emergency actions for suspected viremias. Ecological factors
and the relevance of tourism showed a correlation with the territorial
variability in expenditure. The median cost of one antilarval treatment in public
areas was approximately ?0.12 per inhabitant. Organizational aspects were also
analyzed to identify possible improvements in resource use.
PMID- 28425961
TI - Rapid Texture Optimization of Three-Dimensional Urban Model Based on Oblique
Images.
AB - Seamless texture mapping is one of the key technologies for photorealistic 3D
texture reconstruction. In this paper, a method of rapid texture optimization of
3D urban reconstruction based on oblique images is proposed aiming at the
existence of texture fragments, seams, and inconsistency of color in urban 3D
texture mapping based on low-altitude oblique images. First, we explore
implementing radiation correction on the experimental images with a radiation
procession algorithm. Then, an efficient occlusion detection algorithm based on
OpenGL is proposed according to the mapping relation between the terrain
triangular mesh surface and the images to implement the occlusion detection of
the visible texture on the triangular facets as well as create a list of visible
images. Finally, a texture clustering algorithm is put forward based on Markov
Random Field utilizing the inherent attributes of the images and solve the energy
function minimization by Graph-Cuts. The experimental results display that the
method is capable of decreasing the existence of texture fragments, seams, and
inconsistency of color in the 3D texture model reconstruction.
PMID- 28425960
TI - Studying Lactoferrin N-Glycosylation.
AB - Lactoferrin is a multifunctional glycoprotein found in the milk of most mammals.
In addition to its well-known role of binding iron, lactoferrin carries many
important biological functions, including the promotion of cell proliferation and
differentiation, and as an anti-bacterial, anti-viral, and anti-parasitic
protein. These functions differ among lactoferrin homologs in mammals. Although
considerable attention has been given to the many functions of lactoferrin, its
primary nutritional contribution is presumed to be related to its iron-binding
characteristics, whereas the role of glycosylation has been neglected. Given the
critical role of glycan binding in many biological processes, the glycan moieties
in lactoferrin are likely to contribute significantly to the biological roles of
lactoferrin. Despite the high amino acid sequence homology in different
lactoferrins (up to 99%), each exhibits a unique glycosylation pattern that may
be responsible for heterogeneity of the biological properties of lactoferrins. An
important task for the production of biotherapeutics and medical foods containing
bioactive glycoproteins is the assessment of the contributions of individual
glycans to the observed bioactivities. This review examines how the study of
lactoferrin glycosylation patterns can increase our understanding of lactoferrin
functionality.
PMID- 28425962
TI - Regulation of Ubiquitin Enzymes in the TGF-beta Pathway.
AB - The transforming growth factor-beta (TGF-beta) pathway has a tumor suppressor
role in normal and premalignant cells but promotes oncogenesis in advanced cancer
cells. Components of the pathway are tightly controlled by ubiquitin modifying
enzymes and aberrations in these enzymes are frequently observed to dysregulate
the pathway causing diseases such as bone disorders, cancer and metastasis. These
enzymes and their counterparts are increasingly being tested as druggable
targets, and thus a deeper understanding of the enzymes is required. This review
summarizes the roles of specific ubiquitin modifying enzymes in the TGF-beta
pathway and how they are regulated.
PMID- 28425963
TI - A Multi-Platform Optical Sensor for In Vivo and In Vitro Algae Classification.
AB - Differentiation among major algal groups is important for the ecological and
biogeochemical characterization of water bodies, and for practical management of
water resources. It helps to discern the taxonomic groups that are beneficial to
aquatic life from the organisms causing harmful algal blooms. An LED-induced
fluorescence (LEDIF) instrument capable of fluorescence, absorbance, and
scattering measurements; is used for in vivo and in vitro identification and
quantification of four algal groups found in freshwater and marine environments.
Aqueous solutions of individual and mixed dissolved biological pigments relevant
to different algal groups were measured to demonstrate the LEDIF's capabilities
in measuring extracted pigments. Different genera of algae were cultivated and
the cell counts of the samples were quantified with a hemacytometer and/or
cellometer. Dry weight of different algae cells was also measured to determine
the cell counts-to-dry weight correlations. Finally, in vivo measurements of
different genus of algae at different cell concentrations and mixed algal group
in the presence of humic acid were performed with the LEDIF. A field sample from
a local reservoir was measured with the LEDIF and the results were verified using
hemacytometer, cellometer, and microscope. The results demonstrated the LEDIF's
capabilities in classifying and quantifying different groups of live algae.
PMID- 28425964
TI - Enhancing the Responsivity of Uncooled Infrared Detectors Using Plasmonics for
High-Performance Infrared Spectroscopy.
AB - A lead zirconate titanate (PZT;Pb(Zr0.52Ti0.48)O3) layer embedded infrared (IR)
detector decorated with wavelength-selective plasmonic crystals has been
investigated for high-performance non-dispersive infrared (NDIR) spectroscopy. A
plasmonic IR detector with an enhanced IR absorption band has been designed based
on numerical simulations, fabricated by conventional microfabrication techniques,
and characterized with a broadly tunable quantum cascade laser. The enhanced
responsivity of the plasmonic IR detector at specific wavelength band has
improved the performance of NDIR spectroscopy and pushed the limit of detection
(LOD) by an order of magnitude. In this paper, a 13-fold enhancement in the LOD
of a methane gas sensing using NDIR spectroscopy is demonstrated with the
plasmonic IR detector.
PMID- 28425965
TI - Comparison of CPAP and HFNC in Management of Bronchiolitis in Infants and Young
Children.
AB - Continuous positive airway pressure (CPAP) has been used in infants with
bronchiolitis for decades. Recently, high flow nasal cannula (HFNC) therapy was
introduced We conducted a retrospective study of treatment with CPAP vs. HFNC
between 2013 and 2015, comparing the development in respiratory rate, fraction of
inspired oxygen (FiO2) and heart rate, treatment failure, duration of treatment,
and length of hospital stay. A sample size of 49 children were included. Median
age was 1.9 months. Median baseline pCO2 was 7.4 kPa in both groups, respiratory
rate per minute was 57 vs. 58 (CPAP vs. HFNC). Respiratory rate decreased faster
in the CPAP group (p < 0.05). FiO2 decreased in the CPAP group and increased in
the HFNC group during the first 12 h, whereafter it decreased in both groups. (p
< 0.01). Heart rate development was similar in both groups. Twelve children (55%)
changed systems from HFNC to CPAP due to disease progression. There was no
difference in length of treatment, hospital stay, or transmission to intensive
care unit between the groups. CPAP was more effective than HFNC in decreasing
respiratory rate (RR) and FiO2. No differences were observed in length of
treatment or complications. Further studies should be conducted to compare the
efficacy of the two treatments of bronchiolitis, preferably through prospective
randomized trials.
PMID- 28425966
TI - Endurance Training with or without Glucose-Fructose Ingestion: Effects on Lactate
Metabolism Assessed in a Randomized Clinical Trial on Sedentary Men.
AB - Glucose-fructose ingestion increases glucose and lactate oxidation during
exercise. We hypothesized that training with glucose-fructose would induce key
adaptations in lactate metabolism. Two groups of eight sedentary males were
endurance-trained for three weeks while ingesting either glucose-fructose (GF) or
water (C). Effects of glucose-fructose on lactate appearance, oxidation, and
clearance were measured at rest and during exercise, pre-training, and post
training. Pre-training, resting lactate appearance was 3.6 +/- 0.5 vs. 3.6 +/-
0.4 mg.kg-1.min-1 in GF and C, and was increased to 11.2 +/- 1.4 vs. 8.8 +/- 0.7
mg.kg-1.min-1 by exercise (Exercise: p < 0.01). Lactate oxidation represented
20.6% +/- 1.0% and 17.5% +/- 1.7% of lactate appearance at rest, and 86.3% +/-
3.8% and 86.8% +/- 6.6% during exercise (Exercise: p < 0.01) in GF and C,
respectively. Training with GF increased resting lactate appearance and oxidation
(Training * Intervention: both p < 0.05), but not during exercise (Training *
Intervention: both p > 0.05). Training with GF and C had similar effects to
increase lactate clearance during exercise (+15.5 +/- 9.2 and +10.1 +/- 5.9 mL.kg
1.min-1; Training: p < 0.01; Training * Intervention: p = 0.97). The findings of
this study show that in sedentary participants, glucose-fructose ingestion leads
to high systemic lactate appearance, most of which is disposed non-oxidatively at
rest and is oxidized during exercise. Training with or without glucose-fructose
increases lactate clearance, without altering lactate appearance and oxidation
during exercise.
PMID- 28425967
TI - A Simple and Specific Noncompetitive ELISA Method for HT-2 Toxin Detection.
AB - We developed an HT-2 toxin-specific simple ELISA format with a positive read-out.
The assay is based on an anti-immune complex (IC) scFv antibody fragment, which
is genetically fused with alkaline phosphatase (AP). The anti-IC antibody
specifically recognizes the IC between a primary anti-HT-2 toxin Fab fragment and
an HT-2 toxin molecule. In the IC ELISA format, the sample is added together with
the scFv-AP antibody to the ELISA plate coated with the primary antibody. After
15 min of incubation and a washing step, the ELISA response is read. A
competitive ELISA including only the primary antibody recognizes both HT-2 and T
2 toxins. The anti-IC antibody makes the assay specific for HT-2 toxin, and the
IC ELISA is over 10 times more sensitive compared to the competitive assay. Three
different naturally contaminated matrices: wheat, barley and oats, were used to
evaluate the assay performance with real samples. The corresponding limits of
detection were 0.3 ng/mL (13 ug/kg), 0.1 ng/mL (4 ug/kg) and 0.3 ng/mL (16
ug/kg), respectively. The IC ELISA can be used for screening HT-2 toxin
specifically and in relevant concentration ranges from all three tested grain
matrices.
PMID- 28425968
TI - Deciphering the Multifactorial Susceptibility of Mucosal Junction Cells to HPV
Infection and Related Carcinogenesis.
AB - Human papillomavirus (HPV)-induced neoplasms have long been considered to
originate from viral infection of the basal cell layer of the squamous mucosa.
However, this paradigm has been recently undermined by accumulating data
supporting the critical role of a discrete population of squamo-columnar (SC)
junction cells in the pathogenesis of cervical (pre)cancers. The present review
summarizes the current knowledge on junctional cells, discusses their high
vulnerability to HPV infection, and stresses the potential clinical/translational
value of the novel dualistic model of HPV-related carcinogenesis.
PMID- 28425970
TI - Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and
Abdominal Aortic Aneurysms.
AB - Altered microRNA expression is implicated in cardiovascular diseases. Our
objective was to determine microRNA signatures in thoracic aortic aneurysms
(TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal
aortic specimens. We evaluated the expression of fifteen selected microRNA in
human TAA and AAA operative specimens compared to controls. We observed
significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA
specimens. In contrast, upregulation of miR-146a and downregulation of miR-145
and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486
5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of
TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm
location and common to both thoracic and abdominal pathologies. Thus, changes in
miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p
impact AAAs. This work validates prior studies on microRNA expression in
aneurysmal diseases.
PMID- 28425971
TI - rho0 Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and
Fluxes of Amino Acids.
AB - Solute carrier (SLC) transporters are a diverse group of membrane transporter
proteins that regulate the cellular flux and distribution of endogenous and
xenobiotic compounds. Post-translational modifications (PTMs), such as
ubiquitination, have recently emerged as one of the major regulatory mechanisms
in protein function and localization. Previously, we showed that SLC amino acid
transporters were on average 6-fold de-ubiquitinated and increased amino acid
levels were detected in rho0 cells (lacking mitochondrial DNA, mtDNA) compared to
parental cells. Here, we elucidated the altered functionality of SLC transporters
and their dynamic ubiquitination status by measuring the uptake of several
isotopically labeled amino acids in both human osteosarcoma 143B.TK- and rho0
cells. Our pulse chase analysis indicated that de-ubiquitinated amino acid
transporters in rho0 cells were accompanied by an increased transport rate, which
leads to higher levels of amino acids in the cell. Finding SLC transport
enhancers is an aim of the pharmaceutical industry in order to compensate for
loss of function mutations in these genes. Thus, the ubiquitination status of SLC
transporters could be an indicator for their functionality, but evidence for a
direct connection between de-ubiquitination and transporter activity has to be
further elucidated.
PMID- 28425969
TI - The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and
Cognition Diseases.
AB - Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green
leafy vegetables, orange and yellow fruits that form the macular pigment of the
human eyes. It was hypothesized that they protect against visual disorders and
cognition diseases, such as age-related macular degeneration (AMD), age-related
cataract (ARC), cognition diseases, ischemic/hypoxia induced retinopathy, light
damage of the retina, retinitis pigmentosa, retinal detachment, uveitis and
diabetic retinopathy. The mechanism by which they are involved in the prevention
of eye diseases may be due their physical blue light filtration properties and
local antioxidant activity. In addition to their protective roles against light
induced oxidative damage, there are increasing evidences that L and Z may also
improve normal ocular function by enhancing contrast sensitivity and by reducing
glare disability. Surveys about L and Z supplementation have indicated that
moderate intakes of L and Z are associated with decreased AMD risk and less
visual impairment. Furthermore, this review discusses the appropriate consumption
quantities, the consumption safety of L, side effects and future research
directions.
PMID- 28425972
TI - The Impact of Hyposalivation on Quality of Life (QoL) and Oral Health in the
Aging Population of Al Madinah Al Munawarrah.
AB - Hyposalivation (HS) affects aging individuals by causing pain and discomfort in
the oral cavity. The aim here was to determine the impact of hyposalivation and
the saliva pH on the quality of life and caries status of geriatrics population.
A total of 138 male outpatients attending the Taibah University College of
Dentistry (TUCoD) dental clinic were included in the study. The saliva flow, pH,
Quality of Life (QoL), and caries status were recorded. The QoL was measured
using the Arabic version of the Oral Health Impact Profile-14 (OHIP-14), and the
caries status was recorded using the Decayed, Missed, Filled Teeth (DMFT) index.
The mean age was 67.5 years and 64% were classified as having hyposalivation. The
older respondents tended to have a lower saliva flow and pH compared to their
younger counterparts. There was a significant inverse association (p = 0.02)
between the caries status and mean saliva flow rate. There was also a significant
(p < 0.001) positive correlation between caries and the OHIP-14 scores
(Spearman's rho = 0.293). The prevalence of hyposalivation was relatively high
and there was an inverse relationship between the age, the saliva flow, and pH.
Those with more caries reported significantly poor QoL.
PMID- 28425973
TI - EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the
Early Detection, Characterization and Targeted Treatment of Cancer.
AB - Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the
innate immune system. Activated monocytes (macrophages) phagocytose unwanted
cells/cell fragments from the whole body including solid tissues. As they return
to the blood, macrophages can be used for a non-invasive detection of biomarkers,
thereby providing high sensitivity and specificity, because the intracellular
presence of biomarkers is due to an innate immune response. Flow cytometry
analysis of blood enables the detection of macrophages and phagocytosed
intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for
two fundamental biophysical mechanisms have been exploited. The DNaseX/Apo10
protein epitope is a characteristic of tumor cells with abnormal apoptosis and
proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose
metabolism (Warburg effect), which is concomitant with invasive growth/metastasis
and resistant to radical and apoptosis inducing therapies. The detection of Apo10
and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%)
detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1
represents a drugable target, the EDIM based detection of TKTL1 enables a
targeted cancer therapy using the vitamin derivatives oxythiamine or benfo
oxythiamine.
PMID- 28425975
TI - Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin
Thiazole Derivatives as alpha-Glucosidase Inhibitors.
AB - A series of novel isatin-thiazole derivatives were synthesized and screened for
their in vitro alpha-glucosidase inhibitory activity. These compounds displayed a
varying degree of alpha-glucosidase inhibitory activity with IC50 ranging from
5.36 +/- 0.13 to 35.76 +/- 0.31 MUm as compared to the standard drug acarbose
(IC50 = 817.38 +/- 6.27 MUm). Among the series, compound 6p bearing a hydroxyl
group at the 4-position of the right phenyl and 2-fluorobenzyl substituent at the
N1-positions of the 5-methylisatin displayed the highest inhibitory activity with
an IC50 value of 5.36 +/- 0.13 MUm. Molecular docking studies revealed the
existence of hydrophobic interaction, CH-pi interaction, arene-anion interaction,
arene-cation interaction, and hydrogen bond between these compounds and alpha
glucosidase enzyme.
PMID- 28425974
TI - On the Edge of Research and Technological Application: A Critical Review of
Electromethanogenesis.
AB - The conversion of electrical current into methane (electromethanogenesis) by
microbes represents one of the most promising applications of bioelectrochemical
systems (BES). Electromethanogenesis provides a novel approach to waste
treatment, carbon dioxide fixation and renewable energy storage into a chemically
stable compound, such as methane. This has become an important area of research
since it was first described, attracting different research groups worldwide.
Basics of the process such as microorganisms involved and main reactions are now
much better understood, and recent advances in BES configuration and electrode
materials in lab-scale enhance the interest in this technology. However, there
are still some gaps that need to be filled to move towards its application. Side
reactions or scaling-up issues are clearly among the main challenges that need to
be overcome to its further development. This review summarizes the recent
advances made in the field of electromethanogenesis to address the main future
challenges and opportunities of this novel process. In addition, the present
fundamental knowledge is critically reviewed and some insights are provided to
identify potential niche applications and help researchers to overcome current
technological boundaries.
PMID- 28425976
TI - Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of
Cardiometabolic Genes in Newborn Rats.
AB - Infants born to women with diabetes or obesity are exposed to excess circulating
fuels during fetal heart development and are at higher risk of cardiac diseases.
We have previously shown that late-gestation diabetes, especially in conjunction
with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring.
This study investigated changes in genome-wide histone modifications in newborn
hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin
immunoprecipitation-sequencing revealed a differential peak distribution on gene
promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to
trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR
< 0.1). In the HF-diet exposed offspring, 54% of the annotated genes showed the
gene-activating mark trimethylated lysine 4. Many of these genes (1) are
associated with the "metabolic process" in general and particularly with
"positive regulation of cholesterol biosynthesis" (FDR = 0.03); (2) overlap with
455 quantitative trait loci for blood pressure, body weight, serum cholesterol
(all, FDR < 0.1); and (3) are linked to cardiac disease
susceptibility/progression, based on disease ontology analyses and scientific
literature. These results indicate that maternal HF-diet changes the cardiac
histone signature in offspring suggesting a fuel-mediated epigenetic
reprogramming of cardiac tissue in utero.
PMID- 28425977
TI - Prospective Analysis of the Influence of Sport and Educational Factors on the
Prevalence and Initiation of Smoking in Older Adolescents from Croatia.
AB - The prevalence of smoking among Croatian adolescents is alarmingly high, but no
previous study has prospectively examined the sport- and academic-factors
associated with smoking and smoking initiation. This study aimed to prospectively
examine the associations between scholastic (educational) achievement and sport
factors and smoking in 16- to 18-year-old adolescents. This two-year prospective
cohort study included 644 adolescents who were 16 years of age at baseline (46%
females). Baseline testing was implemented at the beginning of the 3rd year of
high school (September 2014) when participants were 16 years old. Follow-up
testing was completed at the end of the fourth year of high school, which
occurred 20 months later. The evaluated predictor variables were educational
achievement- and sport-related-factors. The outcome variables were (i) smoking at
baseline; (ii) smoking at follow-up; and (iii) smoking initiation over the course
of the study. We assessed the associations between predictors and outcomes using
logistic regression models adjusted for age, gender, socioeconomic status, and
conflict with parents. The educational variables were consistently associated
with smoking, with lower grade-point-average (Baseline: odd ratio (OR): 2.01, 95%
confidence interval (CI): 1.61-2.55; Follow-up: 1.59, 1.31-1.94), more frequent
absence from school (Baseline: OR: 1.40, 95% CI: 1.19-1.69; Follow-up: 1.30, 1.08
1.58), and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10-2.89; Follow
up: 1.57, 1.03-2.41) in children who smoke. Adolescents who reported quitting
sports were at greater odds of being smokers (Baseline: 2.07, 1.31-3.32; Follow
up: 1.66, 1.09-2.56). Sport competitive achievement at baseline was protective
against smoking initiation during following two-year period (0.45, 0.21-0.91).
While the influence of the educational variables on smoking initiation has been
found to be established earlier; sport achievement was identified as a
significant protective factor against initiating smoking in older adolescents.
Results should be used in development of an anti-smoking preventive campaign in
older adolescents.
PMID- 28425978
TI - Validation of mid-infrared spectroscopy for macronutrient analysis of human milk.
AB - OBJECTIVE: Human milk has considerable variation in its composition. Hence, the
nutrient profile is only an estimate and can result in under- or over-estimation
of the intake of preterm infants. Mid-infrared (MIR) spectroscopy is an evolving
technique for analyzing human milk but needs validation before use in clinical
practice. STUDY DESIGN: Human milk samples from 35 mothers delivering at 35 weeks
to term gestation were analyzed for macronutrients by MIR spectroscopy and by
standard laboratory methods using Kjeldahl assay for protein, Mojonnier assay for
fat and high-pressure liquid chromatography assay for lactose. RESULTS: MIR
analysis of the macronutrients in human milk correlated well with standard
laboratory tests with intraclass correlation coefficients of 0.997 for fat, 0.839
for protein and 0.776 for lactose. Agreement between the two methods was
excellent for fat, and moderate for protein and lactose (P<0.001). CONCLUSIONS:
This methodological paper provides evidence that MIR spectroscopy can be used to
analyze macronutrient composition of human milk. Agreement between the
methodologies varies by macronutrient.
PMID- 28425979
TI - Factors leading to rehospitalization for tracheostomized and ventilator-dependent
infants through 2 years of age.
AB - OBJECTIVE: To identify factors leading to readmission for tracheostomized,
ventilator-dependent infants <2 years of age. STUDY DESIGN: Retrospective cohort
study of 117 tracheostomized, ventilator-dependent infants followed through 2
years of age. RESULTS: Home ventilator use (at hospital discharge, 6 and 12
months of age), inhaled steroid use (at 12 and 24 months of age), oxygen
dependence (at 6 and 12 months of age) and tracheostomy (at discharge, 6 and 12
months of age) were increased risks for rehospitalization. Equipment malfunction
throughout the first 2 years also contributed to readmissions. Viral infection,
with rhinovirus/enterovirus the most commonly identified pathogen, was the most
common etiology for rehospitalization. Diuretic use and initial comorbid
diagnoses were not associated with increased risk of rehospitalization.
CONCLUSION: The risk for rehospitalization for infants requiring tracheostomy and
ventilator support was affected by prolonged oxygen use, prolonged ventilator
dependence, inhaled steroid use and equipment malfunction, and was equally
distributed throughout the first 2 years of life.
PMID- 28425980
TI - Possible barriers for genetic counselors returning actionable genetic research
results across state lines.
PMID- 28425981
TI - Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding
our knowledge of genetic disease during fetal development.
AB - PurposeThe aim of this study was to determine the diagnostic yield of whole-exome
sequencing (WES) in fetuses with ultrasound anomalies that resulted in fetal
demise or pregnancy termination. The results were also utilized to aid in the
identification of candidate genes for fetal development and to expand the
clinical phenotype of known genetic conditions.MethodsWES was performed on
specimens from 84 deceased fetuses. Data were analyzed and final results were
classified into one of four categories: positive, possible, negative, and
candidate gene only. WES analysis was predominantly performed in fetus-parent
trios or quads (61%, n=52).ResultsOverall, 20% (n = 17) of cases were positive,
45% (n=38) were possible, 9% (n=7) had only candidate gene variants and 26% (n =
22) tested negative. The diagnostic yield for definitive findings for trio
analysis was 24% (n = 11) compared to 14% (n = 4) for singletons. The most
frequently reported ultrasound anomalies were central nervous system (37%, n =
31), hydrops/edema (36%, n = 30), and cardiovascular anomalies (31%, n =
26).ConclusionOur experience supports the use of WES to identify the molecular
etiology of fetal ultrasound anomalies, to identify candidate genes involved in
fetal development, and to expand our knowledge of the clinical phenotype of known
genetic conditions.
PMID- 28425982
TI - CDH1 germline mutations: different syndromes, same management?
PMID- 28425983
TI - Addressing a patient-controlled approach for genomic data sharing.
PMID- 28425984
TI - Withaferin-A kills cancer cells with and without telomerase: chemical,
computational and experimental evidences.
AB - Maintenance of telomere length is the most consistent attribute of cancer cells.
Tightly connected to their capacity to overcome replicative mortality, it is
achieved either by activation of telomerase or an Alternative mechanism of
Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been
shown to induce DNA damage signalling leading to senescence or apoptosis.
Telomerase inhibitors are considered as potential anticancer drugs but are
ineffective for ALT cancers (~15% of all cancers). Withaferin-A (Wi-A), a major
constituent of the medicinal plant, Withania somnifera (Ashwagandha), has been
shown to exert anti-tumour activity. However, its effect on either telomerase or
ALT mechanisms has not been investigated. Here, by using isogenic cancer cells
with/without telomerase, we found that Wi-A caused stronger cytotoxicity to ALT
cells. It was associated with inhibition of ALT-associated promyelocytic leukemia
nuclear bodies, an established marker of ALT. Comparative analyses of telomerase
positive and ALT cells revealed that Wi-A caused stronger telomere dysfunction
and upregulation of DNA damage response in ALT cells. Molecular computational and
experimental analyses revealed that Wi-A led to Myc-Mad mediated transcriptional
suppression of NBS-1, an MRN complex protein that is an essential component of
the ALT mechanism. The results suggest that Wi-A could be a new candidate drug
for ALT cancers.
PMID- 28425986
TI - P16INK4a upregulation mediated by TBK1 induces retinal ganglion cell senescence
in ischemic injury.
AB - Glaucoma is a leading cause of irreversible blindness worldwide that is
characterized by progressive retinal ganglion cell (RGC) death. However, RGC
senescence as a phase before RGC death, and the mechanism of RGC senescence
remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is
upregulated in acute IOP elevation-induced ischemic retinas mouse model.
Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16)
expression and RGC senescence. Upregulation of TBK1 via plasmid transfection
increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation. The Akt
inhibitor MK-2206 decreased the expression of p16 and Bmi1 serine
phosphorylation. A Bmi1 Ser316 mutation also attenuated TBK1-induced p16
upregulation. Finally, silencing of TBK1 via shRNA knockdown reduced the
expression of p16 as well as Akt and Bmi1 phosphorylation, reducing RGC
senescence in vivo. These data suggest that acute IOP elevation-induced ischemia
increases TBK1 expression, which then increases p16 expression through the Akt-
Bmi1 phosphorylation pathway. This study therefore elucidates a novel mechanism
whereby TBK1 regulates p16 expression and RGC senescence, suggesting a potential
novel treatment strategy for minimizing RGC senescence in retinal ischemia and
glaucoma.
PMID- 28425987
TI - Biological activity of tumor-treating fields in preclinical glioma models.
AB - Glioblastoma is the most common and aggressive form of intrinsic brain tumor with
a very poor prognosis. Thus, novel therapeutic approaches are urgently needed.
Tumor-treating fields (TTFields) may represent such a novel treatment option. The
aim of this study was to investigate the effects of TTFields on glioma cells, as
well as the functional characterization of the underlying mechanisms. Here, we
assessed the anti-glioma activity of TTFields in several preclinical models.
Applying TTFields resulted in the induction of cell death in a frequency- and
intensity-dependent manner in long-term glioma cell lines, as well as glioma
initiating cells. Cell death occurred in the absence of caspase activation, but
involved autophagy and necroptosis. Severe alterations in cell cycle progression
and aberrant mitotic features, such as poly- and micronucleation, preceded the
induction of cell death. Furthermore, exposure to TTFields led to reduced
migration and invasion, which are both biological hallmarks of glioma cells. The
combination of TTFields with irradiation or the alkylating agent, temozolomide
(TMZ), resulted in additive or synergistic effects, and the O6-methyl-guanine DNA
methyltransferase status did not influence the efficacy of TTFields. Importantly,
TMZ-resistant glioma cells were responsive to TTFields application, highlighting
the clinical potential of this therapeutic approach. In summary, our results
indicate that TTFields induce autophagy, as well as necroptosis and hamper the
migration and invasiveness of glioma cells. These findings may allow for a more
detailed clinical evaluation of TTFields beyond the clinical data available so
far.
PMID- 28425985
TI - The cellular senescence of leukemia-initiating cells from acute lymphoblastic
leukemia is postponed by beta-Arrestin1 binding with P300-Sp1 to regulate hTERT
transcription.
AB - Although we previously reported that the self-renewal of leukemia-initiating
cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by
beta-Arrestin1, a multiple-function protein, the cellular senescence is critical
for LICs fate and leukemia progress, and worthy for further investigation. Here
we found that depletion of beta-Arrestin1 extended the population doubling time
and the percentage of senile cells, the signatures of cellular senescence, of B
ALL LICs. Moreover, lack of beta-Arrestin1 enhanced the expression of proteins
(CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and
B-ALL-LICs-derived leukemic mice. Further results showed that loss of beta
Arrestin1 induced senescence of Reh cells through mediating hTERT-telomerase
telomere axis, which was reversed by BIBR1532, the telomerase activity inhibitor.
Importantly, depletion of beta-Arrestin1 decreased the binding of Sp1 to hTERT
promoter at the region of -28 to -36 bp. The anti-sense oligonucleotide of this
key region downregulated the transcription of hTERT and aggravated the senescence
of Reh cells. Further data demonstrated that the depleted beta-Arrestin1 reduced
the interaction of P300 with Sp1, thus to reduce Sp1 binding to hTERT promoter,
downregulate hTERT transcription, decrease telomerase activity, shorten telomere
length, and promote Reh cell senescence. Interestingly, the percentage of senile
cells in B-ALL LICs was decreased, which was negatively correlated to good
prognosis and beta-Arrestin1 mRNA expression in childhood B-ALL patients. Our
study shed a light on the senescence of B-ALL LICs and is regulated by beta
Arrestin1, providing the potential therapeutic target of leukemia by promoting
cellular senescence with a key region of hTERT promoter.
PMID- 28425989
TI - Marine litter: Sea change for plastic pollution.
PMID- 28425990
TI - Ronald Drever (1931-2017).
PMID- 28425992
TI - Ecology: In peril from a perfect pathogen.
PMID- 28425993
TI - Materials science: How to print glass.
PMID- 28425994
TI - Modulating the therapeutic response of tumours to dietary serine and glycine
starvation.
AB - The non-essential amino acids serine and glycine are used in multiple anabolic
processes that support cancer cell growth and proliferation (reviewed in ref. 1).
While some cancer cells upregulate de novo serine synthesis, many others rely on
exogenous serine for optimal growth. Restriction of dietary serine and glycine
can reduce tumour growth in xenograft and allograft models. Here we show that
this observation translates into more clinically relevant autochthonous tumours
in genetically engineered mouse models of intestinal cancer (driven by Apc
inactivation) or lymphoma (driven by Myc activation). The increased survival
following dietary restriction of serine and glycine in these models was further
improved by antagonizing the anti-oxidant response. Disruption of mitochondrial
oxidative phosphorylation (using biguanides) led to a complex response that could
improve or impede the anti-tumour effect of serine and glycine starvation.
Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less
responsive to depletion of serine and glycine, reflecting an ability of activated
Kras to increase the expression of enzymes that are part of the serine synthesis
pathway and thus promote de novo serine synthesis.
PMID- 28425995
TI - Widespread movement of meltwater onto and across Antarctic ice shelves.
AB - Surface meltwater drains across ice sheets, forming melt ponds that can trigger
ice-shelf collapse, acceleration of grounded ice flow and increased sea-level
rise. Numerical models of the Antarctic Ice Sheet that incorporate meltwater's
impact on ice shelves, but ignore the movement of water across the ice surface,
predict a metre of global sea-level rise this century in response to atmospheric
warming. To understand the impact of water moving across the ice surface a broad
quantification of surface meltwater and its drainage is needed. Yet, despite
extensive research in Greenland and observations of individual drainage systems
in Antarctica, we have little understanding of Antarctic-wide surface hydrology
or how it will evolve. Here we show widespread drainage of meltwater across the
surface of the ice sheet through surface streams and ponds (hereafter 'surface
drainage') as far south as 85 degrees S and as high as 1,300 metres above sea
level. Our findings are based on satellite imagery from 1973 onwards and aerial
photography from 1947 onwards. Surface drainage has persisted for decades,
transporting water up to 120 kilometres from grounded ice onto and across ice
shelves, feeding vast melt ponds up to 80 kilometres long. Large-scale surface
drainage could deliver water to areas of ice shelves vulnerable to collapse, as
melt rates increase this century. While Antarctic surface melt ponds are
relatively well documented on some ice shelves, we have discovered that ponds
often form part of widespread, large-scale surface drainage systems. In a warming
climate, enhanced surface drainage could accelerate future ice-mass loss from
Antarctic, potentially via positive feedbacks between the extent of exposed rock,
melting and thinning of the ice sheet.
PMID- 28425996
TI - Glaciology: Ice-shelf stability questioned.
PMID- 28425998
TI - Drivers of salamander extirpation mediated by Batrachochytrium salamandrivorans.
AB - The recent arrival of Batrachochytrium salamandrivorans in Europe was followed by
rapid expansion of its geographical distribution and host range, confirming the
unprecedented threat that this chytrid fungus poses to western Palaearctic
amphibians. Mitigating this hazard requires a thorough understanding of the
pathogen's disease ecology that is driving the extinction process. Here, we
monitored infection, disease and host population dynamics in a Belgian fire
salamander (Salamandra salamandra) population for two years immediately after the
first signs of infection. We show that arrival of this chytrid is associated with
rapid population collapse without any sign of recovery, largely due to lack of
increased resistance in the surviving salamanders and a demographic shift that
prevents compensation for mortality. The pathogen adopts a dual transmission
strategy, with environmentally resistant non-motile spores in addition to the
motile spores identified in its sister species B. dendrobatidis. The fungus
retains its virulence not only in water and soil, but also in anurans and less
susceptible urodelan species that function as infection reservoirs. The combined
characteristics of the disease ecology suggest that further expansion of this
fungus will behave as a 'perfect storm' that is able to rapidly extirpate highly
susceptible salamander populations across Europe.
PMID- 28425999
TI - Three-dimensional printing of transparent fused silica glass.
AB - Glass is one of the most important high-performance materials used for scientific
research, in industry and in society, mainly owing to its unmatched optical
transparency, outstanding mechanical, chemical and thermal resistance as well as
its thermal and electrical insulating properties. However, glasses and especially
high-purity glasses such as fused silica glass are notoriously difficult to
shape, requiring high-temperature melting and casting processes for macroscopic
objects or hazardous chemicals for microscopic features. These drawbacks have
made glasses inaccessible to modern manufacturing technologies such as three
dimensional printing (3D printing). Using a casting nanocomposite, here we create
transparent fused silica glass components using stereolithography 3D printers at
resolutions of a few tens of micrometres. The process uses a photocurable silica
nanocomposite that is 3D printed and converted to high-quality fused silica glass
via heat treatment. The printed fused silica glass is non-porous, with the
optical transparency of commercial fused silica glass, and has a smooth surface
with a roughness of a few nanometres. By doping with metal salts, coloured
glasses can be created. This work widens the choice of materials for 3D printing,
enabling the creation of arbitrary macro- and microstructures in fused silica
glass for many applications in both industry and academia.
PMID- 28426000
TI - Scientific methods: Teach children to spot fake facts.
PMID- 28426001
TI - Remote epitaxy through graphene enables two-dimensional material-based layer
transfer.
AB - Epitaxy-the growth of a crystalline material on a substrate-is crucial for the
semiconductor industry, but is often limited by the need for lattice matching
between the two material systems. This strict requirement is relaxed for van der
Waals epitaxy, in which epitaxy on layered or two-dimensional (2D) materials is
mediated by weak van der Waals interactions, and which also allows facile layer
release from 2D surfaces. It has been thought that 2D materials are the only seed
layers for van der Waals epitaxy. However, the substrates below 2D materials may
still interact with the layers grown during epitaxy (epilayers), as in the case
of the so-called wetting transparency documented for graphene. Here we show that
the weak van der Waals potential of graphene cannot completely screen the
stronger potential field of many substrates, which enables epitaxial growth to
occur despite its presence. We use density functional theory calculations to
establish that adatoms will experience remote epitaxial registry with a substrate
through a substrate-epilayer gap of up to nine angstroms; this gap can
accommodate a monolayer of graphene. We confirm the predictions with
homoepitaxial growth of GaAs(001) on GaAs(001) substrates through monolayer
graphene, and show that the approach is also applicable to InP and GaP. The grown
single-crystalline films are rapidly released from the graphene-coated substrate
and perform as well as conventionally prepared films when incorporated in light
emitting devices. This technique enables any type of semiconductor film to be
copied from underlying substrates through 2D materials, and then the resultant
epilayer to be rapidly released and transferred to a substrate of interest. This
process is particularly attractive in the context of non-silicon electronics and
photonics, where the ability to re-use the graphene-coated substrates allows
savings on the high cost of non-silicon substrates.
PMID- 28426002
TI - Materials science: Crystals aligned through graphene.
PMID- 28426003
TI - A temperate rocky super-Earth transiting a nearby cool star.
AB - M dwarf stars, which have masses less than 60 per cent that of the Sun, make up
75 per cent of the population of the stars in the Galaxy. The atmospheres of
orbiting Earth-sized planets are observationally accessible via transmission
spectroscopy when the planets pass in front of these stars. Statistical results
suggest that the nearest transiting Earth-sized planet in the liquid-water,
habitable zone of an M dwarf star is probably around 10.5 parsecs away. A
temperate planet has been discovered orbiting Proxima Centauri, the closest M
dwarf, but it probably does not transit and its true mass is unknown. Seven Earth
sized planets transit the very low-mass star TRAPPIST-1, which is 12 parsecs
away, but their masses and, particularly, their densities are poorly constrained.
Here we report observations of LHS 1140b, a planet with a radius of 1.4 Earth
radii transiting a small, cool star (LHS 1140) 12 parsecs away. We measure the
mass of the planet to be 6.6 times that of Earth, consistent with a rocky bulk
composition. LHS 1140b receives an insolation of 0.46 times that of Earth,
placing it within the liquid-water, habitable zone. With 90 per cent confidence,
we place an upper limit on the orbital eccentricity of 0.29. The circular orbit
is unlikely to be the result of tides and therefore was probably present at
formation. Given its large surface gravity and cool insolation, the planet may
have retained its atmosphere despite the greater luminosity (compared to the
present-day) of its host star in its youth. Because LHS 1140 is nearby,
telescopes currently under construction might be able to search for specific
atmospheric gases in the future.
PMID- 28426005
TI - Antarctic ice shelf potentially stabilized by export of meltwater in surface
river.
AB - Meltwater stored in ponds and crevasses can weaken and fracture ice shelves,
triggering their rapid disintegration. This ice-shelf collapse results in an
increased flux of ice from adjacent glaciers and ice streams, thereby raising sea
level globally. However, surface rivers forming on ice shelves could potentially
export stored meltwater and prevent its destructive effects. Here we present
evidence for persistent active drainage networks-interconnected streams, ponds
and rivers-on the Nansen Ice Shelf in Antarctica that export a large fraction of
the ice shelf's meltwater into the ocean. We find that active drainage has
exported water off the ice surface through waterfalls and dolines for more than a
century. The surface river terminates in a 130-metre-wide waterfall that can
export the entire annual surface melt over the course of seven days. During
warmer melt seasons, these drainage networks adapt to changing environmental
conditions by remaining active for longer and exporting more water. Similar
networks are present on the ice shelf in front of Petermann Glacier, Greenland,
but other systems, such as on the Larsen C and Amery Ice Shelves, retain surface
water at present. The underlying reasons for export versus retention remain
unclear. Nonetheless our results suggest that, in a future warming climate,
surface rivers could export melt off the large ice shelves surrounding Antarctica
contrary to present Antarctic ice-sheet models, which assume that meltwater is
stored on the ice surface where it triggers ice-shelf disintegration.
PMID- 28426006
TI - Carbon markets: extend, don't limit.
PMID- 28426007
TI - Carbon markets: link with caution.
PMID- 28426009
TI - Global coalition chips away at neglected tropical diseases.
PMID- 28426010
TI - Doom and gloom won't save the world.
PMID- 28426011
TI - Track how technology is transforming work.
PMID- 28426012
TI - Correction.
PMID- 28426013
TI - Fake-drug crackdown, tackling misconduct and Europa's plumes.
PMID- 28426014
TI - French-election fears unite scientists in defence of liberal democracy.
PMID- 28426015
TI - French scientists focus on the big political picture.
PMID- 28426017
TI - Drivers gear up for world's first nanocar race.
PMID- 28426016
TI - Unravelling why shoelace knots fail.
PMID- 28426018
TI - Five hacks for digital democracy.
PMID- 28426019
TI - DNA's secret weapon against knots and tangles.
PMID- 28426020
TI - Social networks push runners to run further and faster than their friends.
PMID- 28426021
TI - US foreign aid saves money as well as lives.
PMID- 28426022
TI - Republican scientists negotiate the Trump era.
PMID- 28426023
TI - Infection: Brief encounter: UTI triggered by vaginal microbiota.
PMID- 28426024
TI - Prostate cancer: Targeting the core of resistance.
PMID- 28426025
TI - Modular low-light microscope for imaging cellular bioluminescence and
radioluminescence.
AB - Low-light microscopy methods are receiving increased attention as new
applications have emerged. One such application is to allow longitudinal imaging
of light-sensitive cells with no phototoxicity and no photobleaching of
fluorescent biomarkers. Another application is for imaging signals that are
inherently dim and undetectable using standard microscopy techniques, such as
bioluminescence, chemiluminescence or radioluminescence. In this protocol, we
provide instructions on how to build a modular low-light microscope (1-4 d) by
coupling two microscope objective lenses, back to back from each other, using
standard optomechanical components. We also provide directions on how to image
dim signals such as those of radioluminescence (1-1.5 h), bioluminescence (~30
min) and low-excitation fluorescence (~15 min). In particular, radioluminescence
microscopy is explained in detail, as it is a newly developed technique that
enables the study of small-molecule transport (e.g., radiolabeled drugs,
metabolic precursors and nuclear medicine contrast agents) by single cells
without perturbing endogenous biochemical processes. In this imaging technique, a
scintillator crystal (e.g., CdWO4) is placed in close proximity to the
radiolabeled cells, where it converts the radioactive decays into optical flashes
detectable using a sensitive camera. Using the image reconstruction toolkit
provided in this protocol, the flashes can be reconstructed to yield high
resolution images of the radiotracer distribution. With appropriate timing, the
three aforementioned imaging modalities may be performed together on a population
of live cells, allowing the user to perform parallel functional studies of cell
heterogeneity at the single-cell level.
PMID- 28426027
TI - Analysis of the germination proteins in Alicyclobacillus acidoterrestris spores
subjected to external factors.
AB - The presence of Alicyclobacillus acidoterrestris, a thermoacidophilic and spore
forming bacterium, in pasteurized acidic juices poses a serious problem for the
processing industry. Therefore, the use of other more effective techniques, such
as high hydrostatic pressure (HHP) and supercritical carbon dioxide (SCCD), is
considered for preserving juices in order to inactivate these bacteria, while
reducing the loss of nutrients and sensory quality of juices. On the other hand,
HHP and SCCD when combined with a moderately elevated temperature can induce
germination of bacterial spores, making them more vulnerable to inactivation. The
spore germination can be also induced by nutrients, such as L-alanine or a
mixture of asparagine, glucose, fructose and potassium ions (AGFK). The aim of
this work was to determine whether applying activating agents: HHP, SCCD and
nutrient germinants (L-alanine and the AGFK mixture), could influence the number
of spores which start to germinate and how this affects the proteins involved in
the spore germination. SDS-PAGE was used to resolve proteins isolated from the A.
acidoterrestris spores. The results that were obtained indicate that the
germination of A. acidoterrestris spores treated with HHP, SCCD and nutrient
germinants reflect the number of spores which start to germinate. The SDS-PAGE
data indicated changes in the level of selected proteins occurring when subjected
to the germination activating factors as well as noticeable differences in those
proteins' molecular weights.
PMID- 28426026
TI - Generation of multipotent induced cardiac progenitor cells from mouse fibroblasts
and potency testing in ex vivo mouse embryos.
AB - Here we describe a protocol to generate expandable and multipotent induced
cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced
expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation
of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus
differs from cell activation and signaling-directed (CASD) reprogramming to
cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas
CASD reprogramming can generate various cell types depending on culture
conditions and raises the possibility of transitioning through a pluripotent cell
state. The protocol describes how to isolate and infect primary fibroblasts;
induce reprogramming and observe iCPC colonies; expand and characterize
reprogrammed iCPCs by immunostaining, flow cytometry and gene expression;
differentiate iCPCs in vitro into cardiac-lineage cells; and test the embryonic
potency of iCPCs via injection into the cardiac crescent of mouse embryos. A
scientist experienced in molecular cell biology and embryology can reproduce this
protocol in 12-16 weeks. iCPCs can be used for studying cardiac biology, drug
discovery and regenerative medicine.
PMID- 28426030
TI - 1,3-N,O-Complexes of late transition metals. Ligands with flexible bonding modes
and reaction profiles.
AB - 1,3-N,O-Chelating ligands are ubiquitous in nature owing to their occurrence as
alpha-chiral amino acids in metalloproteins. These structural units also display
diverse coordination modes, which lend themselves to applications in catalysis as
well as novel fundamental stoichiometric reactivity, including the activation of
inert bonds. This review comments on recent developments in N,O-ligated late
transition metal complexes with an emphasis on preparation, characterization, and
reactivity.
PMID- 28426033
TI - Quantification of Lewis acid induced Bronsted acidity of protogenic Lewis bases.
AB - Proton transfer promoted by the coordination of protogenic Lewis bases to a Lewis
acid is a critical step in catalytic transformations. Although the acidification
of water upon coordination to a Lewis acid has been known for decades, no
attempts have been made to correlate the Bronsted acidity of the coordinated
water molecule with Lewis acid strength. To probe this effect, the pKa's
(estimated error of 1.3 pKa units) in acetonitrile of ten protogenic Lewis bases
coordinated to seven Lewis acids containing Lewis acidities varying 70 kcal mol
1, were computed. To quantify Lewis acid strength, the ability to transfer a
hydride (hydride donor ability) from the respective main group hydride was used.
Coordination of a Lewis acid to water increased the acidity of the bound water
molecule between 20 and 50 pKa units. A linear correlation exhibiting a 2.6 pKa
unit change of the Lewis acid-water adduct per ten kcal mol-1 change in hydride
donor ability of the respective main group hydride was obtained. For the ten
protogenic Lewis bases studied, the coordinated protogenic Lewis bases were
acidified between 10 and 50 pKa units. On average, a ten kcal mol-1 change in
hydride donor ability of the respective main group hydride resulted in about a
2.8 pKa unit change in the Bronsted acidity of the Lewis acid-Lewis base adducts.
Since attempts to computationally investigate the pKa of main group dihydrogen
complexes were unsuccessful, experimental determination of the first reported pKa
of a main group dihydrogen complex is described. The pKa of H2-B(C6F5)3 was
determined to be 5.8 +/- 0.2 in acetonitrile.
PMID- 28426035
TI - Hierarchical BiOI nanostructures supported on a metal organic framework as
efficient photocatalysts for degradation of organic pollutants in water.
AB - Semiconductor-based photocatalysis is a green method for the removal of toxic
organic pollutants by decomposition into harmless products. However, traditional
single-component semiconductors are unable to reach high degradation efficiencies
due to excessive photo charge carrier recombination. The use of hybrid
nanocomposite photocatalysts is a promising strategy for overcoming this problem
by reducing recombination as well as ensuring that large amounts of solar energy
are harvested. Herein, a novel visible-light-active hybrid nanocomposite,
BiOI/MIL-88B(Fe), was successfully synthesized through a simple precipitation
method. In the BiOI/MIL-88B(Fe) composite, both BiOI and MIL-88B(Fe) have
improved charge carrier separation and reduced recombination via a simple Z
scheme mechanism. Photocatalytic degradation of the pollutant RhB was carried out
during irradiation of the as-synthesized composites with simulated solar light,
and the BiOI/MIL-88B(Fe) (2 wt%) composite was found to exhibit the highest
photocatalytic activity among the composites. In addition, colorless phenol and
ciprofloxacin (CIP) degradation experiments were also performed to confirm the
visible light photocatalytic performance of the BiOI/MIL-88B(Fe) hybrid
nanocomposite. Scavenger experiments, PL analysis, NBT transformations, and TA-PL
experiments all supported the proposed Z-scheme mechanism of the BiOI/MIL-88B(Fe)
composite photocatalyst. Moreover, simple separation from solution provides this
3D composite with good reusability and long-term stability.
PMID- 28426036
TI - Formation of the intermetalloid cluster [AgSn18]7- - the reactivity of coinage
metal NHC compounds towards [Sn9]4.
AB - In recent years the formation of intermetalloid clusters by reacting homoatomic
tetrel cluster anions with transition metal complexes has become a promising
synthetic route. Nevertheless a better understanding of the processes occurring
in solution is necessary. Here we present a series of novel polyanionic coinage
metal NHC Zintl clusters [NHCDippM(eta4-Sn9)]3- (M: Cu, Ag, Au; Dipp:
diisopropylphenyl) which are obtained at low temperatures from the reaction of
K4Sn9 with NHCDippMCl (M: Cu-Au) in liquid ammonia. For M = Ag a larger
intermetalloid AgI-bridged nonastannide dimer [(eta4-Sn9)Ag(eta1-Sn9)]7- is also
formed. The stepwise formation of the intermetalloid cluster [AgSn18]7- is
discussed and compared with that of previously reported intermetalloid stannides.
PMID- 28426037
TI - Medicinal plant extracts and plant-derived polyphenols with anthelmintic activity
against intestinal nematodes.
AB - Covering: 2001 up to the end of 2016Polyphenols comprise a structurally diverse
class of natural products. As the development of new anthelmintic drugs against
soil-transmitted helminthiases is an urgent need and polyphenols are widely used
in the treatment of nematode infections in traditional medicine and modern
science, we summarize the state of knowledge in the period of mainly 2001 up to
the end of 2016 on plant extracts with known polyphenolic composition and of
defined polyphenols, mainly from the classes of condensed and hydrolysable
tannins, flavonoids, and phenylpropanoids. The diverse biological activity
against different helminths and the underlying mechanisms are reviewed.
PMID- 28426038
TI - Evaluation of the DGT technique for selective measurement of aluminium and trace
metal concentrations in an acid drainage-impacted coastal waterway.
AB - The performance of DGT-Chelex, DGT-Metsorb and DGT-MBL (Chelex-Metsorb mixed
binding layer) with open and restricted diffusive layers for trace metal (Al, Cd,
Co, Cu, Mn, Ni, Pb, Zn) and oxyanion (As, Mo, Sb, V) measurements, was evaluated
in four natural waters with different pH (range 3.29-7.81). In moderately acidic
(pH ~ 5) and circumneutral (pH ~ 6.3) waters, all three binding layers measured
relatively similar concentrations of Al, while in more alkaline waters (pH ~ 8)
DGT-MBL measured higher concentrations than the other two binding layers. The
measurements of DGT-Chelex and DGT-MBL for Co, Cu, Ni, Pb and Zn, and DGT-Metsorb
and DGT-MBL for As, Sb and V were within 82-119% and not statistically different
(p > 0.05) over the pH range 5-8. Mn measurements by DGT-Chelex and DGT-MBL were
quite similar (95%) at pH 6.3, while DGT-MBL measured higher concentrations than
DGT-Chelex at other pHs. The ratios of measured concentrations with different
diffusive layers (Crestricted/Copen) were between 0.78 and 1.12 for all binding
layers and no statistical differences (p > 0.05) were observed, except for Al at
pH 7.81 and Cu at pH 6.28. DGT-MBL was comparable to DGT-Chelex for the
measurement of most trace metals, and to DGT-Metsorb for the measurement of most
oxyanions, over the pH range 5.05-7.81. Overall, DGT-MBL is superior to the other
tested binding layers because it can simultaneously measure cations and anions,
and accurately measure dissolved Al, across the greatest range of environmental
conditions.
PMID- 28426039
TI - Controlled synthesis of lanthanide-doped Gd2O2S nanocrystals with novel
excitation-dependent multicolor emissions.
AB - Developing multicolor-emitting materials has significant value in many research
fields such as displays, bioimaging, and information storage. The widely adopted
strategies to realize multicolor emission are tuning the material composition,
phase, and size. Herein, the emission color was continuously controlled from
yellow to pink by simply changing the excitation wavelength from 254 nm to 365 nm
for Tb3+/Eu3+ co-doped Gd2O2S NCs. The Gd2O2S NCs with different morphologies,
including nanoplate with various sizes and flower-like, were successfully
prepared by seed-mediated, Na+/Y3+ co-doped, and S concentration-tuned methods.
The results indicated that Na+ ions greatly promote the growth of Gd2O2S NCs and
Y3+ ions have an impact on their shape. Moreover, the PL intensity of the 2%Eu
doped flower-like Na/Y:Gd2O2S (F-NYG) NCs decreased by about 24.7%, 6.8%, and
5.1% under 254 nm, 316 nm, and 348 nm excitation, respectively; this is due to
less non-radiative relaxation paths above the excited state of Eu3+:5D0 at longer
excitation wavelength, which result in a decreased degree of the PL intensity
reduction.
PMID- 28426040
TI - Enhancement of the hole conducting effect of NiO by a N2 blow drying method in
printable perovskite solar cells with low-temperature carbon as the counter
electrode.
AB - In this article, we demonstrate for the first time a mesoscopic printable
perovskite solar cell (PSC) using NiO as the hole transporting material and low
temperature processed carbon as the counter electrode. A single deposition method
assisted by N2 blow drying was used for the deposition of MAPbI3 on a
TiO2/ZrO2/NiO screen-printed electrode. As the final step a low-temperature
processing (i.e. 75 degrees C) carbon counter layer was fabricated on MAPbI3 by
a blade coating method. It is found that the capping layer thickness of MAPbI3
has a significant effect on the device efficiency, especially when NiO is
introduced as a hole transporting material into the structure. Electrochemical
impedance spectroscopy demonstrates good charge transport characteristics for the
device with a thin MAPbI3 capping layer obtained by the N2 blow drying method.
Our best performing device demonstrated a remarkable photovoltaic performance
with a short-circuit current density (Jsc) of 22.38 mA cm-2, an open circuit
voltage (Voc) of 0.97 V, and a fill factor (FF) of 0.50 corresponding to a photo
conversion efficiency (PCE) of 10.83%. Moreover, the un-encapsulated device
exhibited advantageous stability over 1000 h in air in the dark.
PMID- 28426041
TI - Hydrocarbon conversion in the production of synthetic fuels: general discussion.
PMID- 28426042
TI - Antibodies to H2a and H2b histones from the sera of HIV-infected patients
catalyze site-specific degradation of these histones.
AB - Histones and their post-translational modifications have key roles in chromatin
remodeling and gene transcription. Besides intranuclear functions, histones act
as damage-associated molecules when they are released into the extracellular
space. Administration of histones to animals leads to systemic inflammatory and
toxic responses. Autoantibodies with enzymatic activities (abzymes) are
distinctive features of some autoimmune and viral diseases. Electrophoretically
homogeneous IgGs containing no canonical enzymes were isolated from the sera of
HIV-infected patients by chromatography on several affinity sorbents including
anti-histone Sepharose. In contrast to canonical proteases (trypsin,
chymotrypsin, proteinase K), IgGs from HIV-infected patients specifically
hydrolyzed only histones but not many other tested globular proteins. Using MALDI
mass spectrometry the sites of H2a and H2b histone cleavage by anti-histone IgGs
were determined for the first time. One cluster of H2a hydrolysis contains two
major (?) and four moderate (?) cleavage sites: 31-H?R?L?L?R?K G?N-38. One major
and two moderate sites of cleavage were revealed in the second cluster: 14
A?KSRS?SRA?G-22. The third cluster corresponding to the H2a C-terminal part
contains only five minor (?) sites of cleavage: 82-H?LQLAIRNDEELN?KLLG?RV?T?I
102. It was shown that two major and four moderate sites of cleavage were present
in the main cluster of H2b hydrolysis: 46-K?QvhpD?TgiS?SkA?M?GiM?N-63. Two
moderate sites of cleavage correspond to a relatively short 6-mer cluster: 12
K?GskK?A-17. The third relatively long 9-mer cluster contains one major and two
minor sites of H2b cleavage: 80-L?AHYN?KRS?T-88. In the nucleosome core particle,
most of the major and moderate cleavage sites are located at the H2a/H2b
interaction interface. Minor cleavage sites of H2a are involved in binding with
H3 in the nucleosome core. Two moderate cleavage sites of H2b and one major
cleavage site of H2a are located in the disordered N-terminal region interacting
with DNA. According to the crystal structure of the nucleosome core particle, all
identified cleavage sites are expected to affect H2a and H2b folding, nucleosome
assembly, and binding of H2a and H2b with DNA. The existence of H2a and H2b
hydrolyzing abzymes may be very important for the further understanding of
unknown possibilities of immune systems and biological functions of antibodies.
PMID- 28426043
TI - Silica-encapsulated gold nanoparticle dimers for organelle-targeted cellular
delivery.
AB - Silica-encapsulated gold nanoparticle dimers were self-assembled through a single
insertion process using capillary force and can be utilized as an advanced drug
delivery and sensing platform for organelle-targeting in cancer cells.
PMID- 28426044
TI - Lanthanide coordination complexes framed by sodium ions: slow relaxation of the
magnetization in the Dy(III) derivative.
AB - Using a new polydentate Schiff-base ligand (H3L) we isolated three new
tetranuclear isostructural lanthanide complexes with the general formula
[LnNa2(L)4(DMF)4(H2O)2(AcO)2].4DMF.2H2O [Ln = Dy (1), Ho (2), or Er (3)]. The
structural characterization of the complexes reveals that the Na+ ions are
coordinated in the structure which gives them a structure-directing role in the
molecule. The magnetic behavior of the systems was investigated by means of SQUID
magnetometry which revealed that complex 1 exhibits single molecule magnet
behavior at low temperatures which is enhanced by the application of a 2000 Oe
static magnetic field. We were able to extract an effective barrier of Ueff =
43(1) K, however, we show that the consideration of an Orbach relaxation
mechanism being the dominant is not always correct for lanthanides. On the
contrary, we elaborate how in this system the relaxation is caused by a
combination of a direct and a Raman process.
PMID- 28426045
TI - Enzyme-coated Janus nanoparticles that selectively bind cell receptors as a
function of the concentration of glucose.
AB - A method is proposed for controlling the number of nanoparticles bound to cell
membranes via RGDS peptide-integrin interactions. It consists of propelling
nanoparticles bearing the peptides with enzymes (glucose oxidase), which disrupts
biomolecular interactions as a function of the concentration of enzyme substrate
(glucose).
PMID- 28426046
TI - Multicomponent reaction through cooperative trio catalysis incorporating enamine,
Bronsted acid and metal Lewis acid catalysis: a concise route to access chromans.
AB - An atom-economical multicomponent cascade reaction of salicylaldehydes,
cyclohexanones and arylamines has been developed for the synthesis of three-ring
fused chromans. This reaction was achieved through cooperative enamine-metal
Lewis acid assisted Bronsted acid catalysis, furnishing the products in excellent
yields with good diastereoselectivity.
PMID- 28426047
TI - Selective construction of quaternary stereocentres in radical cyclisation
cascades triggered by electron-transfer reduction of amide-type carbonyls.
AB - Radical-radical cyclisation cascades, triggered by single-electron-transfer to
amide-type carbonyls using SmI2-H2O-LiBr, result in the selective construction of
quaternary carbon stereocentres. The cascades deliver tricyclic barbiturates with
four stereocentres in good yield and with excellent diastereocontrol.
PMID- 28426048
TI - Flavored black ginseng exhibited antitumor activity via improving immune function
and inducing apoptosis.
AB - The objective of this project was to examine saponin and carbohydrate conversion,
and to evaluate the antitumor activity of a novel ready-to-eat flavored black
ginseng (FBG). The results of chemical experiments showed that common saponins in
ginseng such as ginsenoside Re, Rg1, Rb1, etc., are almost completely converted
to rare saponins and aglycones such as ginsenoside Rg5, protopanaxadiol (PPD),
etc., and non-reducing sugars such as starch are almost completely degraded into
reducing sugars as affected by garlic juice and high temperature processing.
Furthermore, pharmacological experimental results showed that this novel FBG
could inhibit the growth of tumors in H22 tumor-bearing mice dose-dependently at
the dosage of 250, 500 and 1000 mg kg-1; meanwhile, the results of ELISA, H&E
staining, western blotting and qRT-PCR show that FBG could improve immune
function and induce tumor cell apoptosis.
PMID- 28426049
TI - A Pt-Co3O4-CD electrocatalyst with enhanced electrocatalytic performance and
resistance to CO poisoning achieved by carbon dots and Co3O4 for direct methanol
fuel cells.
AB - Highly efficient electrocatalysts remain huge challenges in direct methanol fuel
cells (DMFCs). Here, a Pt-Co3O4-CDs/C composite was fabricated as an anode
electrocatalyst with low Pt content (12 wt%) by using carbon dots (CDs) and Co3O4
nanoparticles as building blocks. The Pt-Co3O4-CDs/C composite catalyst shows a
significantly enhanced electrocatalytic activity (1393.3 mA mg-1 Pt), durability
(over 4000 s) and CO-poisoning tolerance. The superior catalytic activity should
be attributed to the synergistic effect of CDs, Pt and Co3O4. Furthermore, the Pt
Co3O4-CDs/C catalyst was integrated into a single cell, which exhibits a maximum
power density of 45.6 mW cm-2, 1.7 times the cell based on the commercial 20 wt%
Pt/C catalyst.
PMID- 28426050
TI - Expanding the morphology library of block copolymer self-assemblies with clews of
tubules.
AB - The morphology library of block copolymer (BCP) self-assemblies is limited,
especially as far as tubular structures are concerned. Here, the morphology of
clews of tubules is discovered for the first time by self-assembly of P4VP-b-PS
BCPs with both high asymmetry and very high molecular weight, which successfully
expands the morphology library of BCP self-assemblies.
PMID- 28426052
TI - Artificial molecular motors.
AB - Motor proteins are nature's solution for directing movement at the molecular
level. The field of artificial molecular motors takes inspiration from these tiny
but powerful machines. Although directional motion on the nanoscale performed by
synthetic molecular machines is a relatively new development, significant
advances have been made. In this review an overview is given of the principal
designs of artificial molecular motors and their modes of operation. Although
synthetic molecular motors have also found widespread application as (multistate)
switches, we focus on the control of directional movement, both at the molecular
scale and at larger magnitudes. We identify some key challenges remaining in the
field.
PMID- 28426053
TI - Improved spatial resolution for spot sampling in thermal desorption atomic force
microscopy - mass spectrometry via rapid heating functions.
AB - The key to advancing materials is to understand and control their structure and
chemistry. However, thorough chemical characterization is challenging since
existing techniques characterize only a few properties of the specimen, thereby
necessitating multiple measurement platforms to acquire the necessary
information. The multimodal combination of atomic force microscopy (AFM) and mass
spectrometry (MS) transcends existing analytical capabilities for nanometer scale
spatially resolved correlation of the chemical and physical properties of a
sample surface. One such hybrid system employs heated AFM cantilevers for thermal
desorption (TD) sampling of molecules from a surface and subsequent gas phase
ionization and detection of the liberated species by MS. Herein, we report on the
use of voltage pulse trains to tailor cantilever heating such that spot sampling
size was reduced and mass spectral signal was improved compared to constant
voltage, static heating of the cantilever. Desorption efficiency (DE), defined as
the quotient of the mass spectral signal intensity and the volume of the
desorption crater, was used to judge the effectiveness of a particular tailored
heating function. To guide the development and optimization of the heating
functions and aid in interpreting experimental results, a 1D finite element model
was developed that predicted the cantilever response to different heating
functions. Three tailored heating functions that used different combinations,
magnitudes, and durations of rectangular voltage pulses, were used for surface
spot sampling. The resultant sampling spot size and DE were compared to the same
metrics obtained with the conventional method that uses a single voltage pulse.
Using a model system composed of a thin film of ink containing pigment yellow 74
as a model system, desorption craters shrunk from 2 MUm, using the conventional
approach, to 310 nm using the optimum tailored heating function. This same pulsed
heating function produced a 381* improvement in the DE and an 8* improvement in
spatial resolution compared to the conventional heating approach showing that
signal/amount of material sampled was improved significantly by this new
cantilever heating strategy.
PMID- 28426054
TI - Syntheses, structures, and chiroptical and magnetic properties of chiral clusters
built from Schiff bases: a novel [MnIIMnNa] core.
AB - Chiral clusters with MnIIMnNaI and the new MnIIMnNa cores have been synthesised
employing enantiomerically pure Schiff bases and halide ligands. The new
compounds have been characterized by electronic circular dichroism (ECD) and
magnetic susceptibility.
PMID- 28426055
TI - Droplet manipulation on a structured shape memory polymer surface.
AB - While methods for dynamic tuning of surface wettability to manipulate water
droplets have been widely explored for many applications including digital
microfluidics, those based on dynamically changeable surface morphology have
remained challenging to achieve. In this work, we present a structured shape
memory polymer (SMP) surface which shows dynamically tunable surface wettability
through changeable surface morphology in order to manipulate water droplets. The
structured SMP surface involves a SMP pillar array consisting of nanotextured
small and large pillars which can change its morphology between permanent and
temporary shapes upon thermomechanical loading. Specifically, the structured SMP
surface dynamically creates a surface morphological gradient and changes its
surface wettability during thermally induced shape recovery of the SMP pillar
array. Different wetting characteristics of the structured SMP surface between
permanent and temporary shapes are theoretically predicted and experimentally
verified. Based on these measured wetting characteristics, the structured SMP
surface is designed to demonstrate that the morphological difference between two
shapes under a water droplet overcomes contact angle hysteresis, resulting in
driving a water droplet, when combined with the thermal Marangoni effect.
PMID- 28426056
TI - Chemical pathways for poly-anionic isomerisation in the metastable anions of
tetra-deprotonated naphthalene: an intra-molecular inter-ring proton-transfer.
AB - A surprising chemical pathway involving an intra-molecular proton-transfer
between the two different aromatic rings of naphthalene is revealed while
exploring the isomerisation in the metastable tetra-anionic species of tetra
deprotonated naphthalene. The pathways are explored through quantum-mechanical
computations employing a global reaction route mapping (GRRM) strategy. Notably,
several other pathways traced exhibit interesting aspects of poly-anionic
isomerisation in the multiply-charged metastable molecular anions, which can
provide valuable insights into the mechanisms of ring closure and expansion
leading to species like azulenes, cyclodecapentaene, and phenylvinylacetylene.
The metastable poly-anionic species along the pathways were also analysed using a
nuclear charge stabilisation procedure while employing conventional density
functional theory (DFT) with the B3LYP exchange-correlation functional as well as
long-range and dispersion corrected DFT/omegaB97XD and DFT-D3 methods.
Interestingly, the charge stabilisation method using the DFT/B3LYP was found to
be more reliable than the dispersion corrected methods.
PMID- 28426057
TI - In situ synthesis of fluorescent magnetosomes using an organic membrane as a soft
template.
AB - A novel approach was presented for the in situ synthesis of fluorescent
magnetosomes by biological mineralization and carbonization processes for the
first time. The surface structures, magnetism and fluorescence were studied, and
the cytotoxicity tests and fluorescent trace in liposomes were probed. The
fluorescent magnetosomes exhibit not only unique fluorescence and ferromagnetic
properties but also low toxicity and superior imaging capability.
PMID- 28426058
TI - Radical cations of phenyl silatrane.
AB - Electrochemical oxidation of phenylsilatrane (1) in CH3CN/0.1 M Bu4NPF6 has been
studied by voltammetry, UV-Vis and EPR-coupled spectroelectrochemistry supported
by DFT calculations. One-electron withdrawal from the HOMO of 1, formed with a
predominant contribution of the atrane N atom to the 3c-4e system, results in a
short lived radical cation, in which the atrane nitrogen atom is almost planar
and carries most of the spin density showing strong coupling with the protons of
the axially directed C-H bonds of the three adjacent alpha-methylene groups (g =
2.0037, aalphaHax = 37.93 G, aalphaHlat = 0.23 G and abetaH = 1.8 G). EPR
spectroscopy and DFT calculations attest that the unpaired electron in the
radical cation does not reside at the Si atom.
PMID- 28426059
TI - Evolution of dealloying induced strain in nanoporous gold crystals.
AB - We studied the evolution of dealloying-induced strain along the {111} in a Ag-Au
nano-crystal in situ, during formation of nanoporous gold at the initial stage of
dealloying using Bragg coherent X-ray diffractive imaging. The strain magnitude
with maximum probability in the crystal doubled in 10 s of dealloying. Although
formation of nano-pores just began at the surface, the greatest strain is located
60-80 nm deep within the crystal. Dealloying induced a compressive strain in this
region, indicating volume shrinkage occurred during pore formation. The crystal
interior showed a small tensile strain, which can be explained by tensile
stresses induced by the non-dealloyed region upon the dealloyed region during
volume reduction. A surface strain relaxation developed, attributed to atomic
rearrangement during dealloying. This clearer understanding of the role of strain
in the initial stages of formation of nanoporous gold by dealloying can be
exploited for development of new sensors, battery electrodes, and materials for
catalysis.
PMID- 28426060
TI - Hierarchically scaffolded CoP/CoP2 nanoparticles: controllable synthesis and
their application as a well-matched bifunctional electrocatalyst for overall
water splitting.
AB - Transition metal phosphide (TMP) nanostructures have stimulated increasing
interest for use in water splitting owing to their abundant natural sources and
high activity for the hydrogen evolution reaction (HER) and oxygen evolution
reaction (OER). Typically, the preparation of hierarchical TMPs involves the
utilization of expensive or dangerous phosphorus sources, and, in particular, the
understanding of topotactic transformations of the precursors to crystalline
phases-which could be utilized to enhance electrocatalytic performance-remains
very limited. We, herein, report a controllable preparation of CoP/CoP2
nanoparticles well dispersed in flower-like Al2O3 scaffolds (f-CoP/CoP2/Al2O3) as
a bifunctional electrocatalyst for the HER and OER via the phosphorization of a
flower-like CoAl layered double hydroxide precursor. Characterization by in situ
X-ray diffraction (XRD) monitored the topotactic transformation underlying the
controllable formation of CoP/CoP2via tuning the phosphorization time.
Electrocatalytic tests showed that an f-CoP/CoP2/Al2O3 electrode exhibited a
lower onset potential and higher electrocatalytic activity for the HER and OER in
the same alkaline electrolyte than electrodes of flower-like and powdered
CoP/Al2O3. The enhanced electrochemical performance was experimentally supported
by measuring the electrochemically active surface area. The f-CoP/CoP2/Al2O3
composite further generated a current density of 10 mA cm-2 at 1.65 V when used
as a bifunctional catalyst for overall water splitting. Our results demonstrate
that the preparation route based on the LDH precursor may provide an alternative
for investigating diverse TMPs as bifunctional electrocatalysts for water
splitting.
PMID- 28426061
TI - Self-assembly and anion sensing of metal-organic [M6L2] cages from fluorescent
triphenylamine tri-pyrazoles with dipalladium(ii,ii) corners.
AB - Three hexametal-organic cages [(N^N)6Pd6L2]6+ with syn, syn, syn conformation
were synthesized via the coordination of tris(4-(1H-pyrazol-3-yl)phenyl)amine
ligands and [(N^N)2Pd2(NO3)2](NO3)2 dimetallic corners (N^N = 2,2'-bipyridine for
1; 4,4'-dimethylbipyridine for 2; 1,10-phenanthroline for 3). These hexametal
organic cages exhibit anion sensing toward HSO3- in aqueous solution via
fluorescent titration and NMR spectroscopy studies.
PMID- 28426062
TI - A sandwich-shaped M3L2 zinc(ii) complex containing 1,3,5-tris(dimethyl(pyridin-3
yl)silyl)benzene: selective photoluminescence recognition of diiodomethane.
AB - Self-assembly of Zn(ClO4)2 with 1,3,5-tris(dimethyl(pyridin-3-yl)silyl)benzene
(L) as a new C3-symmetric tridentate N-donor gives rise to a discrete sandwich
shaped M3L2 architecture, [Zn3(MU-OH)3L2](ClO4)3.4CH3CN.2H2O. Its blue
photoluminescence is significantly quenched only by CH2I2 among the various small
molecules, CH2Cl2, CH2Br2, CHCl3, 1,2-dichloroethane, EtOH, CH3CN, benzene,
toluene, and phenol.
PMID- 28426063
TI - Hydrophilic 2,9-bis-triazolyl-1,10-phenanthroline ligands enable selective
Am(iii) separation: a step further towards sustainable nuclear energy.
AB - The first hydrophilic, 1,10-phenanthroline derived ligands consisting of only C,
H, O and N atoms for the selective extraction of Am(iii) from spent nuclear fuel
are reported herein. One of these 2,9-bis-triazolyl-1,10-phenanthroline
(BTrzPhen) ligands combined with a non-selective extracting agent, was found to
exhibit process-suitable selectivity for Am(iii) over Eu(iii) and Cm(iii),
providing a clear step forward.
PMID- 28426064
TI - Dual stimuli-triggered dielectric switching and sensing in a host-guest
cyanometallate framework.
AB - The host-guest hybrid cyanometallate framework (MA)(H2O)[Sr(H2O)2Co(CN)6] (1; MA
= methylammonium) shows thermally and chemically triggered dielectric switching
and sensing via a temperature-driven phase transition and a water-driven
reversible structure transformation between 1 and its dehydrated form
(MA)[SrCo(CN)6].
PMID- 28426065
TI - Correction: Elastic strain effects on catalysis of a PdCuSi metallic glass thin
film.
AB - Correction for 'Elastic strain effects on catalysis of a PdCuSi metallic glass
thin film' by Yiyi Yang et al., Phys. Chem. Chem. Phys., 2015, 17, 1746-1754.
PMID- 28426066
TI - Correction: Metal- and additive-free oxygen-atom transfer reaction: an efficient
and chemoselective oxidation of sulfides to sulfoxides with cyclic diacyl
peroxides.
AB - Correction for 'Metal- and additive-free oxygen-atom transfer reaction: an
efficient and chemoselective oxidation of sulfides to sulfoxides with cyclic
diacyl peroxides' by Shaoyan Gan et al., Org. Biomol. Chem., 2017, 15, 2647-2654.
PMID- 28426067
TI - Bioinspired peptosomes with programmed stimuli-responses for sequential drug
release and high-performance anticancer therapy.
AB - Combination therapy with enhanced therapeutic and antimetastatic efficacy has
become promising for cancer treatment. There is an urgent need to design a co
delivery system to sequentially release the drug pair at desired locations that
can increase the intra-tumoral drug concentration and reduce the side effects.
Inspired by virus architecture and function, herein, we developed a peptosome
(PS)-based co-delivery system, PePm/PS/Curcumin (Cur), for the sequential release
of the therapeutic peptide Pe and chemodrug Cur. PS was formed by the self
assembly of amphiphilic alpha-lactalbumin peptides obtained from enzymatic
partial hydrolysis. Then, PS was self-cross-linked with disulfide bonds utilizing
their endogenous thiol groups. The system is responsive to multiple tumor
microenvironments and releases the drugs at specific tumor locations. First,
after PS accumulation in tumor tissue via the EPR effect, the linkage peptide Pm
in PS can be cleaved by matrix metalloproteinases (MMP) enzymatic hydrolysis. Pe
can stay on the cell surface and antagonize the ErbB-2 receptor expression on the
tumor cells. Moreover, the positively charged nature of remaining Mal-PS/Cur
facilitates tumor cell internalization and induces a subsequent proton-sponge
effect for lysosomal escape. Finally, Cur is released in the cytoplasm via a
reduction-induced PS disassembly due to the high level of intracellular GSH. Both
the in vitro and in vivo results exhibited an enhanced antitumor and
antimetastatic efficacy of this system.
PMID- 28426068
TI - Amplification of the molecular chiroptical effect by low-loss dielectric
nanoantennas.
AB - We report here the chiroptical amplification effect occurring in the hybrid
systems consisting of chiral molecules and Si nanostructures. Under resonant
excitation of circularly polarized light, the hybrid systems show strong CD
induction signals at the optical frequency, which arise from both the electric
and magnetic responses of the Si nanostructures. More interestingly, the induced
CD signals from Si-based dielectric nanoantennas are always larger than that from
Au-based plasmonic counterparts. The related physical origin was disclosed.
Furthermore, compared to the Au-based high-loss plasmonic nanoantennas, Si-based
low-loss structures would generate negligible photothermal effect, which makes Si
nanoantennas an optimized candidate to amplify molecular CD signals with ultralow
thermal damage. Our findings may provide a guideline for the design of novel
chiral nanosensors, which are applicable in the fields of biomedicine and
pharmaceutics.
PMID- 28426069
TI - Gradual modification of ITO particle's crystal structure and optical properties
by pulsed UV laser irradiation in a free liquid jet.
AB - Indium tin oxide (ITO) particle coatings are known for high transparency in the
visible, good conductive properties and near-infrared absorption. These
properties depend on ITO particle's stoichiometric composition, defects and size.
Here we present a method to gradually change ITO particle's optical properties by
a simple and controlled laser irradiation process. The defined irradiation
process and controlled energy dose input allows one to engineer the absorption
and transmission of coatings made from these particles. We investigate the role
of the surrounding solvent, influence of laser fluence and the specific energy
dose targeting modification of the ITO particle's morphology and chemistry by
stepwise laser irradiation in a free liquid jet. TEM, SEM, EDX, XPS, XRD and
Raman are used to elucidate the structural, morphological and chemical changes of
the laser-induced ITO particles. On the basis of these results the observed
modification of the optical properties is tentatively attributed to chemical
changes, e.g. laser-induced defects or partial reduction.
PMID- 28426070
TI - Controllable synthesis of ferromagnetic-antiferromagnetic core-shell NWs with
tunable magnetic properties.
AB - Several nanotechnology applications are based on the promising scheme of highly
anisotropic magnetic nanomaterials. Using this idea, we investigated the
structure, magnetic properties, and interfacial exchange anisotropy effects of
the Ni/Cr2O3 and Fe/Cr2O3 core-shell nanowires (NWs) geometry. A template-based
strategy was developed to synthesize Ni (Fe)-Cr2O3 core-shell NWs, which combines
a wet-chemical route and electrodeposition within the nanopores of the membranes.
Structural determination in correlation with magnetic testing shows that the
crystalline Cr2O3-nanoshells (NSs) cause an enhanced exchange bias, providing an
extra source of anisotropy that leads to their magnetic stability. This core
shell NWs geometry, with enhanced anisotropy, should, therefore, motivate further
study related to the applicability of anisotropic nanostructures. Our design
opens a new pathway to obtain optimized heterostructured nanomaterials exhibiting
tunable magnetic properties.
PMID- 28426071
TI - Ca- and Sr-tetrafluoroisophthalates: mechanochemical synthesis, characterization,
and ab initio structure determination.
AB - New fluorinated coordination polymers were prepared mechanochemically by milling
the alkaline earth metal hydroxides MII(OH)2.xH2O (MII: Ca, Sr) with
tetrafluoroisophthalic acid (H2mBDC-F4). The structures of [{Ca(mBDC
F4)(H2O)2}.H2O] (1) and [{Sr(mBDC-F4)(H2O)2}.H2O] (2) were determined based on ab
initio calculations and their powder X-ray diffraction (PXRD) data. The compounds
are isomorphous and crystallize in the orthorhombic space group P212121. The
determined structures were validated by using extended X-ray absorption (EXAFS)
data. The new materials were thoroughly characterized using elemental analysis,
thermal analysis, magic angle spinning NMR, and attenuated total reflection
infrared spectroscopy. Further characterization methods such as BET, dynamic
vapor sorption, and scanning electron microscopy imaging were also used. Our
investigations indicate that mechanochemistry is an efficient method for
preparing such materials.
PMID- 28426072
TI - In situ hybridization of CoOX nanoparticles on N-doped graphene through one step
mineralization of co-responsive hydrogels.
AB - The in situ hydrothermal mineralization for a mixture of graphene oxide (GO) and
Co-responsive supramolecular hydrogels led to a hybrid graphene aerogel, doped
with Co and N elements. The as-prepared aerogels exhibited a competitive half
wave potential (0.840 V, versus RHE) and peak current density (2.35 mA cm-2) to
that of Pt/C (0.836 V, 2.23 mA cm-2, respectively). Furthermore, they
demonstrated a significantly perfect catalytic efficiency (nearly 100% of 4e-
ORR) toward the oxygen reduction reaction (ORR). Insight into the structural
details of the hybrid aerogels indicates that the CoOX active sites anchored on
the graphene matrix play a central role in the upgrading of the catalytic
performance of graphene aerogels.
PMID- 28426073
TI - Ameliorative effects of pepsin-digested chicken liver hydrolysates on development
of alcoholic fatty livers in mice.
AB - With developments in economics and increasing work loads, alcohol abuse becomes
more and more severe, leading to occurrences of alcoholic liver disease (ALD).
Pepsin-digested chicken liver hydrolysates (CLHs) contain high amounts of
glutamic acid, leucine, lysine, and alanine while the contents of taurine,
anserine, and carnosine are also elevated after pepsin hydrolyzation. The
objectives of this study were to evaluate the protective effects of CLHs against
chronic alcohol consumption. The results indicated that the enlarged (p < 0.05)
sizes of liver and spleen, and serum AST, ALT, and ALKP levels of mice fed with
an alcoholic diet were ameliorated by supplementing with CLHs. Moreover,
increased hepatic immunocyte infiltration shown on the H&E staining and higher (p
< 0.05) hepatic triglyceride contents, TBARS values, and proinflammatory cytokine
levels in alcoholic diet fed mice were also reduced (p < 0.05) by supplementing
with CLHs. Those benefits were attributed to up-regulated fatty acid beta
oxidation and down-regulated fatty acid synthesis, as well as increased (p <
0.05) SOD, CAT, and GPx activities, TEAC levels, and elevated alcohol metabolic
enzymatic activities (ALDH).
PMID- 28426074
TI - Probing the local structure of Prussian blue electrodes by 113Cd NMR
spectroscopy.
AB - We demonstrate that 113Cd NMR is a potent technique to monitor the local
electronic and structural states of the Prussian blue electrode during Li+
intercalation, providing an atomic-scale insight into the reaction mechanism.
PMID- 28426075
TI - Functionalized vinylsilanes via highly efficient and recyclable Pt-nanoparticle
catalysed hydrosilylation of alkynes.
AB - A mild, selective and facile synthesis of vinylsilanes via a recyclable platinum
nanoparticle catalysed hydrosilylation of alkynes is reported. Various
functionalized alkynes are selectively hydrosilylated to furnish functional beta
E vinylsilanes in high yields. The catalytic effectiveness, ease of catalyst
recovery and recyclability of the polysiloxane stabilized Pt-nanoparticle
catalyst are the major achievements of this work. Detailed in situ
characterization using Electron Microscopy and controlled poisoning experiments
supports the participation of Pt-nanoparticles as active catalysts.
PMID- 28426076
TI - An amidato divalent ytterbium cluster: synthesis and molecular structure, its
reactivity to carbodiimides and application in the guanylation reaction.
AB - A divalent ytterbium amidate 1 ([Yb3L6].2C7H8 for short) was synthesized via
amine-elimination of Yb[N(SiMe3)2]2(TMEDA) with an amide proligand N-2,6
diisopropylphenylbenzamide HL (L = 2,6-iPr2C6H3NC(O)Ph) and structurally
characterized to be a trinuclear symmetric cluster. Further studies on the
reduction of iPrN[double bond, length as m-dash]C[double bond, length as m
dash]NiPr by complex 1 provide Yb(iii) complex 2 in hexane-THF ([(YbL2)2(MU
NiPrCNiPr)][YbL3(THF)].C7H8), which is composed of two subunits in a unit cell,
one is a bridged Yb(iii) carbene, just the same as complex 4 ([(YbL2)2(MU
NiPrCNiPr)].3C7H8) obtained in the same reaction in toluene, and the other is a
homoleptic monomeric Yb(iii) amidate (YbL3). It is also found that complex 2
decomposed to complex 3 ([YbL3]2.2C7H8) and 4 at 90 degrees C in toluene.
Complexes 1-4 were confirmed by X-ray structure determination. Furthermore,
complex 4 was proved to be a more active species than its precursor 1 in the
catalytic addition of amines to carbodiimides. Finally, complex 1 was found to be
an excellent pre-catalyst for the guanylation reaction with a wide scope of
substrates.
PMID- 28426077
TI - Robust raspberry-like metallo-dielectric nanoclusters of critical sizes as SERS
substrates.
AB - Raspberry-like nano-objects made of large plasmonic satellites (>10 nm) covering
a central dielectric particle have many potential applications as photonic
materials, superlenses and (bio-) sensors, but their synthesis remains
challenging. Herein, we show how to build stable and robust raspberry-like nano
systems with close-packed satellites, by combining monodisperse silica particles
(80 or 100 nm diameter) and oppositely charged noble metal nanoparticles (Au or
Ag) with well-defined sizes (10-50 nm). The spectral characteristics of their
associated plasmonic resonances (wavelength, linewidth, extinction cross-section)
and the electromagnetic coupling between satellites were observed using the
spatial modulation spectroscopy technique and interpreted through a numerical
model. The composite nano-objects exhibit numerous hot spots at satellite
junctions, resulting in excellent surface-enhanced Raman scattering (SERS)
performance. The SERS efficiency of the raspberry-like clusters is highly
dependent on their structure.
PMID- 28426078
TI - An intravascular bioartificial pancreas device (iBAP) with silicon nanopore
membranes (SNM) for islet encapsulation under convective mass transport.
AB - Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet
viability and functionality due to inadequate mass transfer resulting in islet
hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration
based BAP devices possess enhanced glucose-insulin kinetics, the polymer
membranes used in these devices provide inadequate ultrafiltrate flow rates and
result in excessive thrombosis. Here, we report the silicon nanopore membrane
(SNM), which exhibits a greater hydraulic permeability and a superior pore size
selectivity compared to polymer membranes for use in BAP applications.
Specifically, we demonstrate that the SNM-based intravascular BAP with ~10 and
~40 nm pore sized membranes support high islet viability (>60%) and functionality
(<15 minute insulin response to glucose stimulation) at clinically relevant islet
densities (5700 and 11 400 IE per cm2) under convection in vitro. In vivo studies
with ~10 nm pore sized SNM in a porcine model showed high islet viability (>85%)
at clinically relevant islet density (5700 IE per cm2), c-peptide concentration
of 144 pM in the outflow ultrafiltrate, and hemocompatibility under convection.
These promising findings offer insights on the development of next generation of
full-scale intravascular devices to treat T1D patients in the future.
PMID- 28426079
TI - Oxidation suppression during hydrothermal phase reversion allows synthesis of
monolayer semiconducting MoS2 in stable aqueous suspension.
AB - This letter demonstrates a simple method to achieve high-yields of 1H
semiconducting MoS2 monolayers in concentrated, colloidally-stable aqueous
suspension. The method is based on oxidation suppression during the hydrothermal
processing step used for metal-to-semiconductor phase reversion. Accompanying DFT
calculations on elementary steps in the MoS2 wet oxidation reaction suggest that
a two-site corrosion mechanism is responsible for the observed high reactivity
and low stability of 1T metallic MoS2.
PMID- 28426080
TI - C-reactive protein and interleukin 6 microfluidic immunoassays with on-chip pre
stored reagents and centrifugo-pneumatic liquid control.
AB - We present a fully automated centrifugal microfluidic method for particle based
protein immunoassays. Stick-pack technology is employed for pre-storage and
release of liquid reagents. Quantitative layout of centrifugo-pneumatic particle
handling, including timed valving, switching and pumping is assisted by network
simulations. The automation is exclusively controlled by the spinning frequency
and does not require any additional means. New centrifugal microfluidic process
chains are developed in order to sequentially supply wash buffer based on
frequency dependent stick-pack opening and pneumatic pumping to perform two
washing steps from one stored wash buffer; pre-store and re-suspend
functionalized microparticles on a disk; and switch between the path of the waste
fluid and the path of the substrate reaction product with 100% efficiency. The
automated immunoassay concept is composed of on demand ligand binding, two
washing steps, the substrate reaction, timed separation of the reaction products,
and termination of the substrate reaction. We demonstrated separation of
particles from three different liquids with particle loss below 4% and residual
liquid remaining within particles below 3%. The automated immunoassay concept was
demonstrated by means of detecting C-reactive protein (CRP) in the range of 1-81
ng ml-1 and interleukin 6 (IL-6) in the range of 64-13 500 pg ml-1. The limit of
detection and quantification were 1.0 ng ml-1 and 2.1 ng ml-1 for CRP and 64 pg
ml-1 and 205 pg ml-1 for IL-6, respectively.
PMID- 28426081
TI - Total substitution of dietary fish oil by vegetable oils stimulates muscle
hypertrophic growth in Senegalese sole and the upregulation of fgf6.
AB - The long term effects of fish oil (FO) substitution by increasing the levels of
vegetable oils (VO), 0% (CTR), 50% (VO50) and 100% (VO100), in diets for
Senegalese sole were evaluated in terms of skeletal muscle cellularity and
expression of related genes. After 140 days of feeding, all fish had similar body
weight and length. The inclusion of 50% VO did not result in differences in
muscle cellularity, but dorsal muscle cross-sectional area and fast-twitch fibre
diameter increased in fish fed total FO substitution, whilst fibre density was
reduced (P < 0.05) in relation to CTR. The total number of fibres was similar in
all treatments. FO substitution did not affect the transcript levels of myogenic
genes (myf5, mrf4, myog, myod1, myod2), but resulted in a two-fold increase of
fgf6 transcript levels compared to CTR (P < 0.05). The relative expression of igf
I was higher in VO100 than in VO50, but was similar to CTR. FO substitution
resulted in cellularity changes related to the stimulation of muscle hypertrophic
growth, but not hyperplastic growth, and associated with a nutritional modulation
of fgf6 by dietary VO. This study indicates that 50% VO does not affect the
muscle phenotype, but total FO substitution stimulates muscle hypertrophy.
PMID- 28426082
TI - Deciphering of interactions between platinated DNA and HMGB1 by
hydrogen/deuterium exchange mass spectrometry.
AB - A high mobility group box 1 (HMGB1) protein has been reported to recognize both
1,2-intrastrand crosslinked DNA by cisplatin (1,2-cis-Pt-DNA) and monofunctional
platinated DNA using trans-[PtCl2(NH3)(thiazole)] (1-trans-PtTz-DNA). However,
the molecular basis of recognition between the trans-PtTz-DNA and HMGB1 remains
unclear. In the present work, we described a hydrogen/deuterium exchange mass
spectrometry (HDX-MS) method in combination with docking simulation to decipher
the interactions of platinated DNA with domain A of HMGB1. The global deuterium
uptake results indicated that 1-trans-PtTz-DNA bound to HMGB1a slightly tighter
than the 1,2-cis-Pt-DNA. The local deuterium uptake at the peptide level revealed
that the helices I and II, and loop 1 of HMGB1a were involved in the interactions
with both platinated DNA adducts. However, docking simulation disclosed different
H-bonding networks and distinct DNA-backbone orientations in the two Pt-DNA
HMGB1a complexes. Moreover, the Phe37 residue of HMGB1a was shown to play a key
role in the recognition between HMGB1a and the platinated DNAs. In the cis-Pt-DNA
HMGB1a complex, the phenyl ring of Phe37 intercalates into a hydrophobic notch
created by the two platinated guanines, while in the trans-PtTz-DNA-HMGB1a
complex the phenyl ring appears to intercalate into a hydrophobic crevice formed
by the platinated guanine and the opposite adenine in the complementary strand,
forming a penta-layer pi-pi stacking associated with the adjacent thymine and the
thiazole ligand. This work demonstrates that HDX-MS associated with docking
simulation is a powerful tool to elucidate the interactions between platinated
DNAs and proteins.
PMID- 28426083
TI - Energetic isomers of 1,2,4,5-tetrazine-bis-1,2,4-triazoles with low toxicity.
AB - A series of nitrogen-rich "green" Energetic Materials (EMs), some with improved
sensitivity, thermostability, and very low toxicity, were synthesized on the
basis of 3,5-diamino-1,2,4-triazole (DAT) and 1,2,4,5-tetrazine building blocks.
Since DAT contains several nucleophilic reactive sites, obtaining selective
reactivity and specific isomeric products with 1,2,4,5-tetrazine precursors is a
challenging task. We developed reaction conditions under which specific isomers
could be prepared. On evaluating these compounds for their energetic properties,
we found that N5,N5'-(1,2,4,5-tetrazine-3,6-diyl)-bis(1H-1,2,4-triazole-3,5
diamine) 1 has very high thermostability (onset of decomposition temperature at
357 degrees C) and it is insensitive to impact (Im > 98 J), friction (>360 N)
and electrostatic discharge (2512 mJ). A detonation velocity (Vod) of 8180 m s-1
was calculated for compound 1 and it was found to have extremely low toxicity in
human cells (normal dermal fibroblasts) and in environmental bacteria (Vibrio
fischeri). In combination with oxidants, compound 1 can generate 1225 L of gases
(per kg of energetic mixture of an oxidant and compound 1), which makes this
material a prospective component in solid propellants and a very good candidate
for the development of solid state gas generators for clean fire-extinguishing
systems and for a broad range of other civil and defense applications that
require the use of "green" and insensitive EMs.
PMID- 28426084
TI - Synthesis of 2-amino- and 2-arylazoazulenes via nucleophilic aromatic
substitution of 2-chloroazulenes with amines and arylhydrazines.
AB - The SNAr reaction of 2-chloroazulene derivative 1 with ethoxycarbonyl groups at
the 1,3-positions of the azulene ring with several amines afforded the
corresponding 2-aminoazulenes 3-9 in excellent yields. 2-Chloroazulene (2)
without the electron-withdrawing groups reacted with highly nucleophilic cyclic
amines (i.e., morpholine, piperidine and pyrrolidine) under the high-temperature
conditions in a sealed tube to produce the corresponding 2-aminoazulenes 10-12 in
good yields. 2-Aminoazulenes 10-14 without the electron-withdrawing groups were
also obtained in good yields by the treatment of compounds 3-7 with 100% H3PO4,
but in the cases of the reaction of 8 and 9 with a secondary amine function, the
decomposition of the products resulted. The synthesis of 2-arylazoazulenes 15-18
was also established via the SNAr reaction of 1 with arylhydrazines. The optical
and electrochemical properties of the 2-arylazoazulene derivatives were examined
by UV/Vis spectroscopy, theoretical calculations and voltammetric experiments.
PMID- 28426085
TI - N-Heterocyclic carbene-catalyzed stereoselective construction of olefinic carbon
sulfur bonds via cross-coupling reaction of gem-difluoroalkenes and thiols.
AB - A novel organocatalytic olefinic carbon-sulfur bond forming reaction was
developed. Under the catalysis of 10 mol% stable N-heterocyclic carbene, thiols
undergo direct nucleophilic substitution reaction with gem-difluoroalkenes to
produce alpha-fluorovinyl thioethers in high yields with excellent Z-selectivity.
In this process, bases are not necessary.
PMID- 28426086
TI - Circularly polarised luminescence of pyrenyl di- and tri-peptides with mixed d-
and l-amino acid residues.
AB - Multiple pyrenes as pendants of enantioimpure di-/tripeptides (abbreviated as N
LD-C, N-DL-C, N-LLD-C and N-DDL-C) showed pyrene-origin CPL and CD signals, which
were associated with conflicting CPL-/CD-signs, compared to the corresponding
enantiopure di-/tri-peptides.
PMID- 28426087
TI - A pH-controlled recyclable indolinooxazolidine tagged N-heterocyclic carbene Ru
catalyst for olefin metathesis.
AB - An indolinooxazolidine tagged N-heterocyclic carbene Ru olefin metathesis
catalyst was synthesized and the molecular structure of this new Ru complex was
determined by single crystal X-ray diffraction. This complex is a homogeneous
catalyst and can be recovered by controlling the polarity of the
indolinooxazolidine tag. Under acidic conditions the indolinooxazolidine tag
exists as an open protonated form and under basic conditions the tag is in a
closed form. The distribution of this catalyst in a two-phase system can be
controlled by simply changing the pH, making the recovery of this catalyst easily
obtainable.
PMID- 28426088
TI - Nanoscale imaging and spectroscopy of band gap and defects in polycrystalline
photovoltaic devices.
AB - Improving the power conversion efficiency of photovoltaic (PV) devices is
challenging because the generation, separation and collection of electron-hole
pairs are strongly dependent on details of the nanoscale chemical composition and
defects which are often poorly known. In this work, two novel scanning probe nano
spectroscopy techniques, direct-transmission near-field scanning optical
microscopy (dt-NSOM) and photothermal induced resonance (PTIR), are implemented
to probe the distribution of defects and the bandgap variation in thin lamellae
extracted from polycrystalline CdTe PV devices. dt-NSOM provides high-contrast
spatially-resolved maps of light transmitted through the sample at selected
wavelengths. PTIR provides absorption maps and spectra over a broad spectral
range, from visible to mid-infrared. Results show variation of the bandgap
through the CdTe thickness and from grain to grain that is spatially uncorrelated
with the distributions of shallow and deep defects.
PMID- 28426089
TI - Ferrogels based on entrapped metallic iron nanoparticles in a polyacrylamide
network: extended Derjaguin-Landau-Verwey-Overbeek consideration, interfacial
interactions and magnetodeformation.
AB - A new kind of ferrogel with entrapped metallic iron nanoparticles causing unusual
magnetodeformation is presented. Crosslinked polyacrylamide (PAAm) based
ferrogels embedded with iron nanoparticles (MNPs) were synthesized by free
radical polymerization in aqueous medium. Spherical iron MNPs with average
diameter 66 nm were synthesized by the electrical explosion of wire and modified
by interfacial adsorption of linear polyacrylamide (LPAAm). Extended Derjaguin
Landau-Verwey-Overbeek (xDLVO) calculations based on the superposing of van der
Waals, electrostatic, steric, and magnetic contributions showed that polymeric
encapsulation of nanoparticles by LPAAm is one of the most suitable pathways for
preparing stable aqueous dispersions of iron nanoparticles. Microcalorimetry
confirmed the presence of strong interfacial adhesion forces between LPAAm chains
and the surface of iron nanoparticles. By keeping the same crosslinking density
of a polymer network (i.e. 100 : 1, monomer to crosslinker ratio) and varying the
initial monomer concentration, an influence of the extent of polymer network
reticulation on the mechanical properties and subsequently, magneto-elastic
properties was demonstrated. It was found that the upper limit of the shear
modulus for the synthesis of a new kind of polyacrylamide based ferrogel to
exhibit any usable magnetodeformation under the application of a uniform external
magnetic field of 420 mT is ca. 1 kPa. Magnetodeformation of cylindrical ferrogel
samples was observed in the form of an overall volume contraction accompanied by
a homogeneous decrease in all dimensions. The deformation was found to be maximum
(around 10%) for the aspect ratio of 1/1 and it was lower and similar for the
samples with 1/2 and 2/1 aspect ratios. Such a type of magnetic response is
significantly different from the behavior observed in the existing reports on
ferroelastomers.
PMID- 28426090
TI - Oleuropein down-regulated IL-1beta-induced inflammation and oxidative stress in
human synovial fibroblast cell line SW982.
AB - Rheumatoid arthritis (RA) is a chronic and systemic inflammatory autoimmune
disease mainly characterized by aggressive hyperproliferation of synovial
fibroblasts (SFs). It is accompained by a massive infiltration of inflammatory
immune cells inducing progressive matrix degradation, destruction of cartilage
and bone erosion through the production of inflammatory mediators. Oleuropein is
the most prevalent phenolic component in olive leaves, seed, pulp and peel of
unripe olives and is responsible for the characteristic bitter taste of
unprocessed olives. This secoiridoid possesses well-documented pharmacological
properties, including antioxidant and anti-inflammatory properties, and is
available as a food supplement in Mediterranean countries. However, to date, anti
arthritic effects of oleuropein on SFs have not been yet elucidated. Thus, the
aim of the present study was to investigate the potential effects of oleuropein,
on IL-1beta-induced production of inflammatory mediators and oxidative stress in
the human synovial sarcoma cell line (SW982). In order to gain a better insight
into mechanisms of action, signaling pathways were also explored. Cell viability
was determined using the sulforhodamine B (SRB) assay. The expression of
inflammatory cytokines IL-6, TNF-alpha, MMP-1 and MMP-3 was evaluated by ELISA.
Moreover, changes in the protein expression of cyclooxygenase (COX)-2, microsomal
prostaglandin E synthase-1 (mPGES-1) as well as mitogen-activated protein kinase
(MAPKs), nuclear factor kappa B (NF-kappaB), and nuclear factor-erythroid 2
related and heme oxygenase-1 (HO-1) signalling pathways were analysed by western
blot. Oleuropein exerted anti-inflammatory and anti-oxidant effects via down
regulation of MAPK and NF-kappaB signaling pathways and induction of Nrf2-linked
HO-1 controlling the production of inflammatory mediators decreasing IL-6 and TNF
alpha cytokines, MMP-1 and MMP-3 levels and mPGES-1 and COX-2 overexpression.
Thus, oleuropein might provide a basis for developing a new dietary strategy for
the prevention and management of RA.
PMID- 28426091
TI - Distinguishing between homogeneous and heterogeneous hydrogen-evolution catalysis
with molecular cobalt complexes.
AB - Molecular proton-reduction catalysts can decompose under the acidic conditions
required for hydrogen evolution, resulting in formation of secondary metal
containing materials. Using an electrochemical quartz crystal microbalance
(EQCM), we report a new method for probing electrodeposition of catalytically
active heterogeneous material from molecular precursors. The data collected
suggest that EQCM can provide a direct measure of the homogeneity of molecular
proton-reduction catalysts over short timescales.
PMID- 28426092
TI - Correction: High precision, localized proton gradients and fluxes generated by a
microelectrode device induce differential growth behaviors of pollen tubes.
AB - Correction for 'High precision, localized proton gradients and fluxes generated
by a microelectrode device induce differential growth behaviors of pollen tubes'
by Chengzhi Hu et al., Lab Chip, 2017, 17, 671-680.
PMID- 28426093
TI - Biophysical properties, thermal stability and functional impact of 8-oxo-7,8
dihydroguanine on oligonucleotides of RNA-a study of duplex, hairpins and the
aptamer for preQ1 as models.
AB - 8-10: A better understanding of the effects that oxidative lesions have on RNA is
of importance to understand their role in the development/progression of disease.
8-oxo-7,8-dihydroguanine was incorporated into RNA to understand its structural
and functional impact on RNA:RNA and RNA:DNA duplexes, hairpins and pseudoknots.
One to three modifications were incorporated into dodecamers of RNA [AAGA GGG
AUGAC] resulting in thermal destabilization (Delta T m - 10 degrees C per
lesion). Hairpins with tetraloops c-UUCG*-g* ( ), a-ACCG-g* ( ), c-UUG*G*-g* ( )
and c-ACG*G*-g* ( ) were modified and used to determine thermal stabilities,
concluding that: (i) modifying the stem leads to destabilization unless adenosine
is the opposing basepair of 8-oxoGua; (ii) modification at the loop is position-
and sequence-dependent and varies from slight stabilization to large
destabilization, in some cases leading to formation of other secondary structures
(hairpin->duplex). Functional effects were established using the aptamer for preQ
1 as model. Modification at G5 disrupted the stem P1 and inhibited recognition of
the target molecule 7-methylamino-7-deazaguanine (preQ 1 ). Modifying G11 results
in increased thermal stability, albeit with a K d 4-fold larger than its
canonical analog. These studies show the capability of 8-oxoG to affect structure
and function of RNA, resulting in distinct outcomes as a function of number and
position of the lesion.
PMID- 28426094
TI - SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription.
AB - SIRT7 is an NAD+-dependent protein deacetylase that regulates cell growth and
proliferation. Previous studies have shown that SIRT7 is required for RNA
polymerase I (Pol I) transcription and pre-rRNA processing. Here, we took a
proteomic approach to identify novel molecular targets and characterize the role
of SIRT7 in non-nucleolar processes. We show that SIRT7 interacts with numerous
proteins involved in transcriptional regulation and RNA metabolism, the majority
of interactions requiring ongoing transcription. In addition to its role in Pol I
transcription, we found that SIRT7 also regulates transcription of snoRNAs and
mRNAs. Mechanistically, SIRT7 promotes the release of P-TEFb from the inactive
7SK snRNP complex and deacetylates CDK9, a subunit of the elongation factor P
TEFb, which activates transcription by phosphorylating serine 2 within the C
terminal domain (CTD) of Pol II. SIRT7 counteracts GCN5-directed acetylation of
lysine 48 within the catalytic domain of CDK9, deacetylation promoting CTD
phosphorylation and transcription elongation.
PMID- 28426095
TI - Models of global gene expression define major domains of cell type and tissue
identity.
AB - The current classification of cells in an organism is largely based on their
anatomic and developmental origin. Cells types and tissues are traditionally
classified into those that arise from the three embryonic germ layers, the
ectoderm, mesoderm and endoderm, but this model does not take into account the
organization of cell type-specific patterns of gene expression. Here, we present
computational models for cell type and tissue specification derived from a
collection of 921 RNA-sequencing samples from 272 distinct mouse cell types or
tissues. In an unbiased fashion, this analysis accurately predicts the three
known germ layers. Unexpectedly, this analysis also suggests that in total there
are eight major domains of cell type-specification, corresponding to the
neurectoderm, neural crest, surface ectoderm, endoderm, mesoderm, blood mesoderm,
germ cells and the embryonic domain. Further, we identify putative genes
responsible for specifying the domain and the cell type. This model has
implications for understanding trans-lineage differentiation for stem cells,
developmental cell biology and regenerative medicine.
PMID- 28426096
TI - Managing the sequence-specificity of antisense oligonucleotides in drug
discovery.
AB - All drugs perturb the expression of many genes in the cells that are exposed to
them. These gene expression changes can be divided into effects resulting from
engaging the intended target and effects resulting from engaging unintended
targets. For antisense oligonucleotides, developments in bioinformatics
algorithms, and the quality of sequence databases, allow oligonucleotide
sequences to be analyzed computationally, in terms of the predictability of their
interactions with intended and unintended RNA targets. Applying these tools
enables selection of sequence-specific oligonucleotides where no- or only few
unintended RNA targets are expected. To evaluate oligonucleotide sequence
specificity experimentally, we recommend a transcriptomics protocol where two or
more oligonucleotides targeting the same RNA molecule, but with entirely
different sequences, are evaluated together. This helps to clarify which changes
in cellular RNA levels result from downstream processes of engaging the intended
target, and which are likely to be related to engaging unintended targets. As
required for all classes of drugs, the toxic potential of oligonucleotides must
be evaluated in cell- and animal models before clinical testing. Since potential
adverse effects related to unintended targeting are sequence-dependent and
therefore species-specific, in vitro toxicology assays in human cells are
especially relevant in oligonucleotide drug discovery.
PMID- 28426097
TI - Landscape of RNA polyadenylation in E. coli.
AB - Polyadenylation is thought to be involved in the degradation and quality control
of bacterial RNAs but relatively few examples have been investigated. We used a
combination of 5?-tagRACE and RNA-seq to analyze the total RNA content from a
wild-type strain and from a poly(A)polymerase deleted mutant. A total of 178
transcripts were either up- or down-regulated in the mutant when compared to the
wild-type strain. Poly(A)polymerase up-regulates the expression of all genes
related to the FliA regulon and several previously unknown transcripts, including
numerous transporters. Notable down-regulation of genes in the expression of
antigen 43 and components of the type 1 fimbriae was detected. The major
consequence of the absence of poly(A)polymerase was the accumulation of numerous
sRNAs, antisense transcripts, REP sequences and RNA fragments resulting from the
processing of entire transcripts. A new algorithm to analyze the position and
composition of post-transcriptional modifications based on the sequence of
unencoded 3?-ends, was developed to identify polyadenylated molecules. Overall
our results shed new light on the broad spectrum of action of polyadenylation on
gene expression and demonstrate the importance of poly(A) dependent degradation
to remove structured RNA fragments.
PMID- 28426098
TI - Targeting chromatin defects in selected solid tumors based on oncogene addiction,
synthetic lethality and epigenetic antagonism.
AB - Background: Although the role of epigenetic abnormalities has been studied for
several years in cancer genesis and development, epigenetic-targeting drugs have
historically failed to demonstrate efficacy in solid malignancies. However,
successful targeting of chromatin remodeling deficiencies, histone writers and
histone reader alterations has been achieved very recently using biomarker-driven
and mechanism-based approaches. Epigenetic targeting is now one of the most
active areas in drug development and could represent novel therapeutic
opportunity for up to 25% of all solid tumors. Material and methods: We reviewed
preclinical and clinical studies that described epigenetic oncogenic addictions,
synthetic lethal relationships or epigenetic antagonisms in chromatin regulators.
Experimental approaches, their clinical relevance and applicability, as well as
corresponding on-going studies are described. Results: The most successful
approaches that have been clinically validated so far include the targeting of
the BRD4-NUT fusion transcript in NUT-midline carcinoma by BET (Bromodomain Extra
Terminal) inhibitors, and the use of EZH2 (Enhancer of Zest Homolog 2) inhibitors
in SMARCB1-deficient malignant rhabdoid tumors and SMARCA4-deficient ovarian
small cell carcinomas. Clinical validation is still required for other synthetic
lethal relationships or epigenetic antagonisms, including those described between
EZH2 inhibitors and deficiencies in components of the Polycomb or SWI/SNF
chromatin-remodeling complexes (including BAP1, ARID1A and PBRM1 subunits), as
well as between the CREBBP and EP300 histone acetylases. Further, interplays
between epigenetic modifiers and non-epigenetic cellular processes might be
therapeutically exploited, and combinatorial strategies could be envisioned to
overcome resistance or to sensitize cells to already approved drugs. Conclusion:
Epigenetic-targeting drugs have historically failed proving efficacy in solid
malignancies when used broadly, but novel mechanism-based approaches in
molecularly selected patient populations have facilitated recent successes in
proof-of-concept studies in solid tumors. Appropriate clinical trial design and
molecular patient selection will be key for the success of epigenetic modifiers
in solid tumours.
PMID- 28426099
TI - Improving brain penetration of kinase inhibitors in lung cancer patients with
oncogene dependency.
PMID- 28426100
TI - Don't forget the host: a potential role for germinal polymorphisms as markers for
checkpoint inhibitors.
PMID- 28426101
TI - Cancer risk among 21st century blood transfusion recipients.
AB - Background: Some carcinogenic viruses are known to be transmissible by blood
transfusion. Intensive viral screening of transfused blood now exists in most
countries. In the UK, high-sensitivity nucleic acid amplification tests for
hepatitis C virus were introduced in 1999 and it was thought that this would
reduce, and possibly eliminate, transfusion-related liver cancer. We aimed to
investigate cancer risk in recipients of blood transfusion in 2000 or after.
Methods: A total of 1.3 million UK women recruited in 1998 on average were
followed for hospital records of blood transfusion and for cancer registrations.
After excluding women with cancer or precancerous conditions before or at the
time of transfusion, Cox regression yielded adjusted relative risks of 11 site
specific cancers for women with compared to without prior blood transfusion.
Results: During follow up, 11 274 (0.9%) women had a first recorded transfusion
in 2000 or after, and 1648 (14.6%) of them were subsequently diagnosed with
cancer, a mean 6.8 years after the transfusion. In the first 5 years after
transfusion there were significant excesses for most site-specific cancers
examined, presumably because some had preclinical cancer. However, 5 or more
years (mean 8 years) after blood transfusion, there were significant excess risks
only for liver cancer (adjusted relative risk = 2.63, 95%CI 1.45-4.78) and for
non-Hodgkin lymphoma (adjusted relative risk = 1.74, 1.21-2.51). When analyses
were restricted to those undergoing hip or knee replacement surgery, the
commonest procedure associated with transfusion, these relative risks were not
materially altered. Conclusions: In a large cohort of UK women, transfusions in
the 21st century were associated with long-term increased risks of liver cancer
and non-Hodgkin lymphoma. Some of these malignancies may have been caused by
carcinogenic agents that are not currently screened for in transfused blood.
PMID- 28426102
TI - Infection-related complications during treatment for childhood acute
lymphoblastic leukemia.
AB - Background: Comprehensive studies on neutropenia and infection-related
complications in patients with acute lymphoblastic leukemia (ALL) are lacking.
Patients and methods: We evaluated infection-related complications that were
grade >=3 on National Cancer Institute's Common Terminology Criteria for Adverse
Events (version 3.0) and their risk factors in 409 children with newly diagnosed
ALL throughout the treatment period. Results: Of the 2420 infection episodes,
febrile neutropenia and clinically or microbiologically documented infection were
seen in 1107 and 1313 episodes, respectively. Among documented infection
episodes, upper respiratory tract was the most common site (n = 389), followed by
ear (n = 151), bloodstream (n = 147), and gastrointestinal tract (n = 145)
infections. These episodes were more common during intensified therapy phases
such as remission induction and reinduction, but respiratory and ear infections,
presumably viral in origin, also occurred during continuation phases. The 3-year
cumulative incidence of infection-related death was low (1.0+/-0.9%, n = 4),
including 2 from Bacillus cereus bacteremia. There was no fungal infection
related mortality. Age 1-9.9 years at diagnosis was associated with febrile
neutropenia (P = 0.002) during induction and febrile neutropenia and documented
infection (both P < 0.001) during later continuation. White race was associated
with documented infection (P = 0.034) during induction. Compared with low-risk
patients, standard- and high-risk patients received more intensive therapy during
early continuation and had higher incidences of febrile neutropenia (P < 0.001)
and documented infections (P = 0.043). Furthermore, poor neutrophil surge after
dexamethasone pulses during continuation, which can reflect the poor bone marrow
reserve, was associated with infections (P < 0.001). Conclusions: The incidence
of infection-related death was low. However, young age, white race, intensive
chemotherapy, and lack of neutrophil surge after dexamethasone treatment were
associated with infection-related complications. Close monitoring for prompt
administration of antibiotics and modification of chemotherapy should be
considered in these patients.
PMID- 28426103
TI - Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a
single centre experience and review of the literature.
AB - Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly
improved survival for patients with advanced melanoma in recent years. Anti-CTLA
4 and anti-PD1 antibodies have been approved following large Phase III trials.
Immune-related neurological toxicity of varying severity has been reported in the
literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab
and pembrolizumab is reported as <1% in published clinical trials. We aimed to
identify the incidence of neurotoxicity in our institution across anti-CTLA4 and
anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab. We
also review the existing literature and propose an investigation and management
algorithm. Methods: All patients with advanced melanoma treated with ipilimumab,
nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab (ipi +
nivo), managed at the Royal Marsden Hospital between September 2010 and December
2015, including patients on (published) clinical trials were included. Medical
records for each patient were reviewed and information on neurotoxicity recorded.
A systematic search strategy was performed to collate existing reports of
neurological toxicity. Results: In total, 413 immunotherapy treatment episodes in
352 patients were included, with median follow-up of 26.7 months. Ten cases of
neurotoxicity were recorded, affecting 2.8% of patients overall, ranging from
grade 1 to 4, affecting both central and peripheral nervous systems. A rate of
14% was noted with ipi + nivo. Three of five patients commenced on
corticosteroids responded to these. Six patients had made a full recovery at the
time of reporting. A favorable radiological response was found in 7 of the 10
cases. Unusual presentations are described in detail. Conclusions: Neurological
toxicity is not uncommon, and may be more frequent in patients treated with
combination ipi + nivo. Patterns of presentation and response to treatment are
varied. A prompt and considered approach is required to optimize outcomes in this
group of patients.
PMID- 28426104
TI - A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in
patients with previously treated non-small-cell lung cancer.
AB - Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC)
and small-cell lung cancer. However, no direct comparisons between amrubicin and
docetaxel, a standard treatment for NSCLC, have been reported. Patients and
methods: We conducted a randomized phase III trial of Japanese NSCLC patients
after one or two chemotherapy regimens. Patients were randomized to amrubicin (35
mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks).
Outcomes included progression-free survival, overall survival, tumor responses,
and safety. Results: Between October 2010 and June 2012, 202 patients were
enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0
months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were
comparable in the amrubicin and docetaxel groups, respectively. The overall
response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel
groups, respectively (P = 0.45). The disease control rate was 55.7% in both
groups. Adverse events occurred in all patients, and included grade >=3
neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and
docetaxel groups, respectively, grade >=3 leukopenia occurred in 63.3% and 70.7%,
and grade >=3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the
amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in
the amrubicin group, three were considered related to amrubicin and resolved
without treatment discontinuation. Conclusions: This was the first phase III
study to compare amrubicin and docetaxel in patients with pretreated NSCLC.
Amrubicin did not significantly improve the primary endpoint of PFS compared with
docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).
PMID- 28426105
TI - The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in
ductal carcinoma in situ of the breast.
AB - Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct
in invasive breast cancer, but their clinical role in ductal carcinoma in situ
(DCIS) has not been ascertained. Patients and methods: We evaluated the
prevalence and clinical relevance of TILs in a well annotated series of 1488
consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria
for TILs evaluation were pre-defined involving the International Immuno-Oncology
Biomarker Working Group. TILs percentage was considered both as a continuous and
categorical variable. Levels of TILs were examined for their associations with
ipsilateral breast event (IBE), whether in situ or invasive. Results: Of the 1488
patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% >=50% peri
ductal stromal lymphocytes. The interobserver agreement in TILs evaluation,
measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95
0.97). At univariable analysis, clinical factors significantly associated with
TILs (P <=0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2
positive DCIS were more frequently associated with TILs (24% of patients with
TILs >=50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%)
and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association
between TILs as a continuous variable and the risk of IBEs. Likewise, when
patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and
>=50%), no statistically significant association was observed (10-year cumulative
incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). Conclusion:
TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a
significant association between TILs and the 10-year risk of IBE, our data
suggest that immunotherapies might be considered in subsets of DCIS patients.
PMID- 28426107
TI - Controversies and consensus in the innovation access for cancer therapy in the
European countries: on the subject of metastatic prostate cancer.
AB - Innovative cancer therapies and advances in drug development have created new
hopes for patients and health providers. The purpose of this article was to
evaluate the discrepancies in the assessment of the magnitude of benefit of four
new drugs (abiraterone acetate, enzalutamide, cabazitaxel, radium-223 dichloride)
for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The
comparison was done among three European countries (UK, Germany and France) and
Canada, according to the statement of each country and to the European Society of
Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale. Whereas those drugs
are authorized by the European Medical Agency, one can observed that clear
discrepancies in the magnitude of benefit assessment exist between selected
countries, as well as between national pricing evaluation agencies and ESMO.
However, price setting and reimbursement decisions remain national responsibility
with differences in assessment of the medical value of new treatment across
countries, leading to a heterogeneous accessibility to cancer treatments. In
conclusion, several procedures have to be implemented to overcome the patchwork
of administrative assessments. Among them, the assessment of medical value should
be based on independent statements of learned societies, and the harmonization of
access to cancer therapy in Europe has to be driven by a common European
reimbursement and pricing policy.
PMID- 28426106
TI - Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non
small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7
trial.
AB - Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib,
significantly improved progression-free survival (PFS), time-to-treatment failure
(TTF) and objective response rate (ORR) versus gefitinib in patients with
epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung
cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS)
data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus
gefitinib 250 mg/day in treatment-naive patients with stage IIIb/IV NSCLC and a
common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned
after ~213 OS events and >=32-month follow-up. OS was analysed by a Cox
proportional hazards model, stratified by EGFR mutation type and baseline brain
metastases. Results: Two-hundred and twenty-six OS events had occurred at the
data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS
(afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) =
0.86, 95% confidence interval (CI) 0.66-1.12, P = 0.2580]. Prespecified subgroup
analyses showed similar OS trends (afatinib versus gefitinib) in patients with
exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58-1.17, P =
0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62-1.36, P =
0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least
one subsequent systemic anti-cancer treatment following discontinuation of
afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third
generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF
and ORR data were significantly improved with afatinib. Conclusion: In LUX-Lung
7, there was no significant difference in OS with afatinib versus gefitinib.
Updated PFS (independent review), TTF and ORR data were significantly improved
with afatinib. Clinicaltrials.gov identifier: NCT01466660.
PMID- 28426108
TI - MRI assessment and outcomes in patients receiving neoadjuvant chemotherapy only
for primary rectal cancer: long-term results from the GEMCAD 0801 trial.
AB - Background: Primary chemotherapy has been tested as a possible approach for
patients with high risk features but predicted clear mesorectal margins on
preoperative MRI assessment. This study investigates the prognostic relevance of
baseline and post-treatment MRI and pathology staging in rectal cancer patients
undergoing primary chemotherapy. Patients and methods: Forty-six patients with T3
tumour > =2 mm from the mesorectal fascia were prospectively treated with
Neoadjuvant Capecitabine, Oxaliplatin and Bevacizumab prior to surgery between
2009 and 2011. The baseline and post-treatment MRI: T, Nodal and Extra-mural
venous invasion (EMVI) status were recorded as well as post-treatment MRI Tumour
regression grade (TRG) and modified-RECIST assessment of tumour length. The post
treatment pathology (yp) assessments of T3 substage, N, EMVI and TRG status were
also recorded. Three-year disease-free survival (DFS) and cumulative incidence of
recurrence were estimated by using the Kaplan-Meier product-limit method, and Cox
proportional hazards models were used to determine associations between staging
and response on MRI and pathology with survival outcomes. Results: About 46
patients underwent neoadjuvant chemotherapy alone for high risk margin safe
primary rectal cancer. The median follow-up was 41 months, 5 patients died and 11
patients experienced relapse (2 local, 8 distant and 1 both). In total 23/46
patients were identified with MRI features of EMVI at baseline. mrEMVI positive
status carried independent prognostic significance for DFS (P = 0.0097) with a
hazard ratio of 31.33 (95% CI: 2.3-425.4). The histopathologic factor that was of
independent prognostic importance was a final ypT downstage of ypT3a or less,
hazard ratio: 14.0 (95% CI: 1.5-132.5). Conclusions: mrEMVI is an independent
prognostic factor at baseline for poor outcomes in rectal cancer treated with
neoadjuvant chemotherapy while <=ypT3a is associated with an improvement in DFS.
Future preoperative therapy evaluation in rectal cancer patients will need to
stratify treatment according to baseline EMVI status as a crucial risk factor for
recurrence in patients with predicted CRM clear rectal cancer.
PMID- 28426109
TI - Defining research priorities without biases: what is the optimal process?
PMID- 28426110
TI - Closing the gap in travel medicine: reframing research questions for a new era.
AB - Background: Travel medicine needs are changing. New patterns of travel, including
greater travel by individuals from emerging economies with different values in
costs, risks and benefits, must be considered. This review aims to (1) highlight
selected studies that have been published that address previously identified gaps
in knowledge; (2) propose possible ways to consider questions regarding travel
medicine practice for travelers from emerging economies, underscoring priorities
for research focusing on these important populations; (3) highlight potential
deficiencies in relevance of current international guidelines as they pertain to
travelers from emerging economies; (4) frame research questions for travelers
from emerging economies and (5) consider roles for ISTM in closing the gap.
Methods: We reviewed past travel medicine research priorities published in 2010
to identify publications that responded to some research questions posed. We also
reviewed CDC and WHO recommendations and assessed their applicability to
travelers from emerging economies. Results: Recent publications have responded to
some research questions, but gaps remain and new questions have emerged. Re
framing of several key research questions is needed for travelers from emerging
economies. Discussion: A new challenge looms for traditional travel medicine
fields to identify and attend to knowledge and guideline gaps, particularly to
rethink questions regarding travel medicine to make them relevant for travelers
from emerging economies. The International Society of Travel Medicine is well
positioned to assist emerging economies assess their resources and needs,
formulate research priorities and tailor the development of travel medicine into
a framework aligned to their requirements.
PMID- 28426111
TI - Importation of yellow fever into China: assessing travel patterns.
AB - Rapid increase in trade and a growing air passenger market encourages high travel
volume between the regions associated with increasing risks of such importations
including China. Eleven Chinese workers infected during the 2016 yellow fever
(YF) outbreak in Angola imported YF into China highlighting the potential for
spread into Asia. Using outbound and inbound travel data, we assessed travel
patterns from and to YF endemic countries in relation to China. Among YF endemic
countries, Angola has the second highest number of travellers into China and also
receives the second highest number of Chinese visitors. We estimated that China
needs around half a million YF vaccine doses to cover their population travelling
to YF endemic countries. The recent importation cases into China also unmasked
the low YF vaccination coverage among Chinese travellers and workers to Angola,
indicating the need to ensure better adherence to the International Health
Regulations.
PMID- 28426112
TI - Travel medicine perspectives of select travel medicine experts practicing in the
Asia-Pacific region.
PMID- 28426113
TI - Health problems among Thai tourists returning from India.
AB - Background: The number of Thai tourists visiting India is increasing each year.
Most studies investigating health problems among international travellers to
India have focused on travellers from Europe or North America, and the
applicability of these studies to Asian travellers is unknown. Methods: This
cross-sectional study used data collected from Thai tourists who had recently
completed a trip to India. A questionnaire on demographic data, travel
characteristics, pre-travel health preparation, and health problems during the
trip to India was administered. All participants were also invited to answer a
follow-up questionnaire 15 days after their arrival. Results: The study included
1,304 Thai tourists returning from India between October 2014 and March 2015.
Sixty-two percent were female. Overall median age was 49 years, and the median
length of stay was 10.6 days. Most were package tourists, and 52% (675) reported
health problems during their trip. Common health problems were cough, runny nose,
and sore throat (31.1%), followed by musculoskeletal problems (21.7%), fever
(12.7%), diarrhea (9.8%) and skin problems (6.6%). Other reported problems were
related to the eyes/ears (2.1%), animal exposure (1.9%) and accidents (0.8%). We
found that several factors may be associated with the incidence of health
problems among these tourists, including travelling style and travel health
preparation. In the follow-up questionnaire, 16.8% of the participants reported
new or additional symptoms that developed after their return to Thailand.
Respiratory symptoms were still the most common health problems during this 15
day period. Conclusions: Over half (52%) of Thai tourists experienced health
problems during their trip to India. The most common health problem was not
travellers' diarrhoea, as would be expected from published studies. Rather,
respiratory and musculoskeletal problems were common symptoms. This information
will be useful in pre-travel assessment and care. Our findings may indicate that
health risks among travellers vary by nationality.
PMID- 28426114
TI - Infectious diseases and migrant worker health in Singapore: a receiving country's
perspective.
AB - Background: Approximately 1.4 million migrant workers reside in Singapore,
presenting unique infectious disease challenges to both migrants and Singapore.
Methods: A Pubmed, MEDLINE (Ovid), EBSCO Host (Global Health) and Google Scholar
search was performed for both peer, non-peer reviewed articles and reports
relevant to migrant health in Singapore, published between 1 January 1989 and 1
September 2016. Additional studies were identified from citations within searched
articles. We also reviewed published data and policy documents from the
Ministries of Health and Manpower, Singapore. Results: A significant proportion
of malaria, enteric fevers, hepatitis A and E and tuberculosis diagnosed in
Singapore involve migrant workers. From the 1990-2000 through 2009-11, while
malaria and hepatitis A cases have decreased and remain sporadic, enteric fevers
and tuberculosis cases have increased, possibly due to greater influx of migrant
workers. Hepatitis E numbers remain low but migrant workers account for half of
diagnosed cases. In an interplay of immune naivete, work and living conditions,
migrants in the construction industry are at higher risk of arboviral infections
such as dengue, Zika and chikungunya. Infections such as chikungunya were likely
introduced into Singapore by travellers including migrant workers from the Indian
subcontinent but autochthonous transmission continued due to the presence of
competent mosquito vectors. There is less data regarding sexual health, networks
and infections amongst migrant workers, an area which merits further attention.
Conclusions: Migrant workers appear to be at higher risk than Singaporeans for
specific infectious diseases, probably due to a complex interplay of several
factors, including higher disease prevalence in their countries of origin, socio
economic factors, their living conditions in Singapore and financial, language
and cultural barriers to healthcare access. Receiving countries need improved
surveillance, expansion of preventive measures and decreased barriers to
healthcare access for migrant workers.
PMID- 28426115
TI - Health problems of newly arrived migrants and refugees in Europe.
AB - Background: The number of migrants and refugees in Europe in the past few years
has increased dramatically due to war, violence or prosecutions in their
homeland. Migration may affect physical, mental and social health. The objective
of this article is to assess migrants and refugees' health problems, and to
recommend appropriate interventions. Methods: A PubMed search of published
articles on health problems of newly arrived migrants and refugees was conducted
from 2003 through 2016, focusing on the current refugee crisis in Europe.
Results: In addition to communicable diseases, such as respiratory,
gastrointestinal and dermatologic infections, non-communicable diseases,
including chronic conditions, mental and social problems, account for a
significant morbidity burden in newly arrived migrants and refugees. Vaccine
preventable diseases are also of outmost importance. The appropriate management
of newly arrived refugees and migrants' health problems is affected by barriers
to access to health care including legal, communication, cultural and
bureaucratic difficulties. There is diversity and lack of integration regarding
health care provision across Europe due to policy differences between health care
systems and social services. Conclusion: There is a notable burden of
communicable and non-communicable diseases among newly arrived migrants and
refugees. Provision of health care at reception and temporary centres should be
integrated and provided by a multidisciplinary team Appropriate health care of
migrants and refugees could greatly enhance their health and social status which
will benefit also the host countries at large.
PMID- 28426116
TI - Portuguese expatriates' health in Angola and Mozambique-a cross-sectional study:
increasing awareness and need for more surveillance.
AB - Background: Increasing numbers of expatriates are working in sub-Saharan Africa.
There is little published data on the complex population and this survey aimed at
understanding expatriate morbidity by accessing self-reported health problems and
malaria preventive practices. Methods: A cross-sectional web-based survey was
conducted targeting Portuguese expatriates in Angola and Mozambique. Logistic
regression analysis explored factors associated with self-reported health
problems and psychological symptoms in the previous 3 months. Results: A total
sample of 352 adult Portuguese urban civil occupational expatriates was obtained.
Median length of expatriation was 3 years. Considering a 3-month timeframe, one
in five expatriates reported new health problems and need of medical assistance,
5% were hospitalized and 64% reported general psychological symptoms. Less than
2% of subjects were on malaria chemoprophylaxis. Having chronic health conditions
doubled the reporting of new health problems. Increasing length of expatriation
was associated with decreasing reporting of general psychological symptoms.
Directors and executive managers and expatriates living alone tended to report
more general psychological symptoms. Conclusion: Expatriate communities deserve
enhanced surveillance for the health issues that affect them. This will improve
evidence-based preparation and intervention by public and travel health
practitioners.
PMID- 28426117
TI - Identifying the gaps in Nepalese migrant workers' health and well-being: a review
of the literature.
AB - Background: The health and well-being of migrant workers from low-income
countries is often neglected in travel medicine. This article uses Nepal as a
case study to highlight key issues affecting this particular group of
international travellers. Methods: This narrative review used a comprehensive
systematic literature search to identify relevant studies on Nepal. The included
articles were thematically analysed leading to four key themes or risk factors.
Results: The search found 18 articles from which we identified 3 key themes
related directly to migrant workers: (1) sexual risk taking; (2) occupational
health and (3) lifestyles, and a fourth theme related to partners and family of
migrant workers who are left behind in Nepal. Of the 18 included articles, 11
articles discussed sexual risk taking and HIV, whilst considerably fewer focused
on work-related risk factors and lifestyle factors in migrant workers.
Conclusions: Migrant workers who are generally healthy appear to be similar to
tourist travellers in regarding sexual health as a key issue related to being
abroad. Risky sexual behaviour increases in individuals separated from their
usual sexual partners, away from their own communities and families, leading to
the so-called 'situational disinhibition'. Considering the recent media coverage
of deaths and injuries among migrant workers in the Middle East, it is
interesting to see that their sexual health is more prevalent in the research
literature. This article argues that travel medicine should provide more emphasis
to the health and well-being of migrant workers as a highly vulnerable group of
travellers with additional impact on the health of those left behind.
PMID- 28426119
TI - Dual HER2 inhibition and pathological complete response in early breast cancer:
increasing success of treatment by improving patient selection.
PMID- 28426118
TI - Closing the gap in travel medicine.
PMID- 28426120
TI - A phase II study of a human anti-PDGFRalpha monoclonal antibody (olaratumab, IMC
3G3) in previously treated patients with metastatic gastrointestinal stromal
tumors.
AB - Background: This study evaluated tumor response to olaratumab (an anti-PDGFRalpha
monoclonal antibody) in previously treated patients with metastatic
gastrointestinal stromal tumor (GIST) with or without PDGFRalpha mutations
(cohorts 1 and 2, respectively). Patients and methods: Patients received
olaratumab 20 mg/kg intravenously every 14 days until disease progression, death,
or intolerable toxicity occurred. Outcome measures were 12-week tumor response,
progression-free survival (PFS), overall survival (OS), and safety. Results: Of
30 patients enrolled, 21 patients received >=1 dose of olaratumab. In the
evaluable population (cohort 1, n = 6; cohort 2, n = 14), no complete response
(CR) or partial response (PR) was observed. Stable disease (SD) was observed in 3
patients (50.0%) in cohort 1 and 2 patients (14.3%) in cohort 2. Progressive
disease (PD) was observed in 3 patients (50.0%) in cohort 1 and 12 patients
(85.7%) in cohort 2. The 12-week clinical benefit rate (CR + PR + SD) (90% CI)
was 50.0% (15.3-84.7%) in cohort 1 and 14.3% (2.6-38.5%) in cohort 2. SD lasted
beyond 12 weeks in 5 patients (cohort 1, n = 3; cohort 2, n = 2). Median PFS (90%
CI) was 32.1 (5.0-35.9) weeks in cohort 1 and 6.1 (5.7-6.3) weeks in cohort 2.
Median OS was not reached in cohort 1 and was 24.9 (14.4-49.1) weeks in cohort 2.
All patients in cohort 1 and 9 (64.3%) in cohort 2 experienced an olaratumab
related adverse event (AE), most commonly fatigue (38.1%), nausea (19.0%), and
peripheral edema (14.3%). Two grade >=3 olaratumab-related events were reported
(cohort 1, syncope; cohort 2, hypertension). Conclusions: Olaratumab had an
acceptable AE profile in patients with GIST. While there was no apparent effect
on PFS in patients without PDGFRalpha mutations, patients with PDGFRalpha-mutant
GIST (all with D842V mutations) treated with olaratumab had longer disease
control compared with historical data for this genotype. ClinicalTrials.gov
Identifier: NCT01316263.
PMID- 28426121
TI - Phase II study of cabazitaxel with or without abiraterone acetate and prednisone
in patients with metastatic castrate resistant prostate cancer after prior
docetaxel and abiraterone acetate.
PMID- 28426122
TI - Efficacy of androgen deprivation therapy and the role of oxidative stress.
PMID- 28426123
TI - Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled
randomized discontinuation study.
AB - Background: Cabozantinib, an orally bioavailable inhibitor of tyrosine kinases
including MET, AXL, and VEGF receptors, was assessed in patients with
hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation
trial with nine tumor-type cohorts. Patients and methods: Eligible patients had
Child-Pugh A liver function and <=1 prior systemic anticancer regimen, completed
>=4 weeks before study entry. The cabozantinib starting dose was 100 mg daily.
After an initial 12-week cabozantinib treatment period, patients with stable
disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version
1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead
in stage was objective response rate (ORR) at week 12, and the primary endpoint
of the randomized stage was progression-free survival (PFS). Results: Among the
41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a
confirmed partial response (PR). The week 12 disease control rate (PR or SD) was
66% (Asian subgroup: 73%). Of patients with >=1 post-baseline scan, 78% had tumor
regression, with no apparent relationship to prior sorafenib therapy. Alpha
fetoprotein (AFP) response (>50% reduction from baseline) occurred in 9 of the 26
(35%) patients with elevated baseline AFP and >=1 post-baseline measurement.
Twenty-two patients with SD at week 12 were randomized. Median PFS after
randomization was 2.5 months with cabozantinib and 1.4 months with placebo,
although this difference was not statistically significant. Median PFS and
overall survival from Day 1 in all patients were 5.2 and 11.5 months,
respectively. The most common grade 3/4 adverse events, regardless of
attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia
(15%). Dose reductions were utilized in 59% of patients. Conclusions:
Cabozantinib has clinical activity in HCC patients, including objective tumor
responses, disease stabilization, and reductions in AFP. Adverse events were
managed with dose reductions. Trial registration number: NCT00940225.
PMID- 28426124
TI - Propofol suppresses LPS-induced nuclear accumulation of HIF-1alpha and tumor
aggressiveness in non-small cell lung cancer.
AB - Tumor hypoxia has been recognized as a characteristic of the tumor
microenvironment and promotes metastasis in a variety of types of cancer.
However, in lung cancer, the role of hypoxia-inducible factor 1alpha (HIF-1alpha)
in modulating the cellular response to the inflammation-related microenvironment
remains unclear. In the present study, enhanced expression of HIF-1alpha
accompanied by an increased ROS level was observed in lipopolysaccharide (LPS)
stimulated non-small cell lung cancer (NSCLC) cells. In addition, propofol, a
general anesthetic, was found to significantly reduce the LPS-induced
upregulation of HIF-1alpha and ROS in a dose-dependent manner. Further study
showed that propofol may antagonize the role of LPS in activating HIF-1alpha
through attenuating the protein stability and nuclear localization of HIF-1alpha.
Moreover, knockdown of HIF-1alpha attenuated expression of mesenchymal marker,
vimentin, but promoted the expression of epidermal marker, E-cadherin, in the LPS
treated NSCLC cells. Notably, LPS-induced epithelial-to-mesenchymal transition
(EMT) was notably suppressed by propofol treatment. Consistently, a wound healing
assay revealed that propofol abrogated LPS-stimulated migration of NSCLC cells
while overexpression of HIF-1alpha reversed the effects of propofol. Similarly,
we investigated the influence of propofol on the invasive capability of NSCLC
cells. Western blot and RT-PCR analyses indicated that both knockdown of HIF
1alpha and treatment of propofol attenuated the LPS-activated expression of MMP2
and MMP9 which are necessary for tumor invasion. However, results from the
Transwell assay confirmed that propofol also suppressed cell invasion by
decreasing HIF-1alpha expression in the LPS-treated NSCLC cells. Analysis of
clinical specimens demonstrated abnormal expression of HIF-1alpha in NSCLC
tissues and a poor prognosis in patients with elevated HIF-1alpha expression.
Thus, the present study suggests a potential strategy for NSCLC by targeting HIF
1alpha.
PMID- 28426125
TI - Cerclage Use: A Review of 3 National Guidelines.
AB - Importance: Preterm birth is a major contributor to perinatal morbidity and
mortality. The most common intervention performed to improve perinatal outcomes
for a woman experiencing cervical dilation in the second trimester without signs
or symptoms of preterm labor is the cerclage. Objective: We sought to review and
compare available national guidelines on cerclage use. Evidence Acquisition: We
performed a descriptive review of 3 national guidelines on cerclage: The American
Congress of Obstetricians and Gynecologists Practice Bulletin on "Cerclage for
the Management of Cervical Insufficiency," Green-top Guideline from the Royal
College of Obstetricians and Gynaecologists entitled "Cervical Cerclage," and the
Society of Obstetricians and Gynaecologists of Canada Clinical Practice Bulletin
entitled "Cervical Insufficiency and Cervical Cerclage." Guidelines were
compared, and the following aspects of cerclage use for prevention of preterm
delivery were summarized: indications and contraindications, risk factors for
cervical insufficiency, perioperative considerations, and timing of removal.
Recommendations and strength of evidence were reviewed based on each guideline's
method of reporting. The references were compared with regard to the total number
of randomized control trials, Cochrane Reviews, and systematic reviews/meta
analyses cited. Results: The variations highlighted in the guidelines reflect the
heterogeneity of the literature contributing to guidelines and the challenges of
diagnosing and managing cervical insufficiency. Conclusions: A cohesive
international guideline may improve safety and quality and optimize patient
outcomes. Target Audience: Obstetricians and gynecologists, family physicians.
Learning Objectives: After completing this activity, the learner should be better
able to outline variations in indications and contraindications for cervical
cerclage use by international guideline, identify variation in perioperative
considerations for cervical cerclage use by international guideline, and
recognize variation in timing of removal by international guideline.
PMID- 28426126
TI - Actinomyces in Pregnancy: A Review of the Literature.
AB - Importance: Actinomyces is commonly found in many areas of the body where it
derives a benefit without harming the host. When it does infect the host during
pregnancy, is that infection a threat to the obstetric patient and does that
infection cause adverse pregnancy outcomes? Objective: The aim of this study was
to review what is known about Actinomyces infections and the impact of an
Actinomyces infection on pregnancy outcomes. Evidence Acquisition: A PubMed
search was undertaken with the search years unlimited to April 1, 2016, and
restricted to articles in English. The search terms included "actinomyces,"
"pregnancy," "prenatal," "maternal," "actinomyces infection," "pregnancy,"
"chorioamnionitis," "preterm labor," "premature birth," or "postpartum
actinomyces." Results: Eighteen of the 154 identified articles are the basis of
this review. Actinomyces is a rod-like positive bacterium. The diagnosis of an
Actinomyces infection can be by culture or Gram stain. Actinomyces is commensal
and typically only infects after a mucosal break or lesion. Seventeen cases were
identified in pregnancy. Ten cases were complicated by chorioamnionitis and a
preterm delivery. A nidus leading to infection was identified in 12 of the cases
including women with a cervical cerclage, dental abscesses, appendicitis, renal
actinomycosis, and ovarian abscesses. Adverse pregnancy outcomes have been linked
with periodontal disease, but treatment did not prevent preterm delivery in a
randomized, blinded, controlled trial. Conclusions: Actinomyces infections in
pregnancy are rare but, if they occur, have been linked primarily with preterm
deliveries. Target Audience: Obstetricians and gynecologists, family physicians.
Learning Objectives: After completing this activity, the learner should be better
able to identify the areas of the body where Actinomyces infections occur and how
the infections typically occur, identify the pathophysiologic changes that occur
during pregnancy that might lead to an Actinomyces infection and how that
infection may affect pregnancy outcomes, and describe the treatment for mild and
severe Actinomyces infections.
PMID- 28426127
TI - Postpartum Hypertension: Etiology, Diagnosis, and Management.
AB - Importance: Postpartum hypertension complicates approximately 2% of pregnancies
and, similar to antepartum severe hypertension, can have devastating consequences
including maternal death. Objective: This review aims to increase the knowledge
and skills of women's health care providers in understanding, diagnosing, and
managing hypertension in the postpartum period. Results: Hypertension
complicating pregnancy, including postpartum, is defined as systolic blood
pressure 140 mm Hg or greater and/or diastolic blood pressure 90 mm Hg or greater
on 2 or more occasions at least 4 hours apart. Severe hypertension is defined as
systolic blood pressure 160 mm Hg or greater and/or diastolic blood pressure 110
mm Hg or greater on 2 or more occasions repeated at a short interval (minutes).
Workup for secondary causes of hypertension should be pursued, especially in
patients with severe or resistant hypertension, hypokalemia, abnormal creatinine,
or a strong family history of renal disease. Because severe hypertension is known
to cause maternal stroke, women with severe hypertension sustained over 15
minutes during pregnancy or in the postpartum period should be treated with fast
acting antihypertension medication. Labetalol, hydralazine, and nifedipine are
all effective for acute management, although nifedipine may work the fastest. For
persistent postpartum hypertension, a long-acting antihypertensive agent should
be started. Labetalol and nifedipine are also both effective, but labetalol may
achieve control at a lower dose with fewer adverse effects. Conclusions and
Relevance: Providers must be aware of the risks associated with postpartum
hypertension and educate women about the symptoms of postpartum preeclampsia.
Severe acute hypertension should be treated in a timely fashion to avoid
morbidity and mortality. Women with persistent postpartum hypertension should be
administered a long-acting antihypertensive agent. Target Audience: Obstetricians
and gynecologists, family physicians. Learning Objectives: After completing this
activity, the learner should be better able to assist patients and providers in
identifying postpartum hypertension; provide a framework for the evaluation of
new-onset postpartum hypertension; and provide instructions for the management of
acute severe and persistent postpartum hypertension.
PMID- 28426128
TI - Hippocampal electrical stimulation disrupts associative learning when targeted at
dentate spikes.
AB - KEY POINTS: Dentate spikes are fast fluctuations of hilar local-field potentials
that take place during rest and are thought to reflect input arriving from the
entorhinal cortex to the hippocampus. During dentate spikes, neuronal firing in
hippocampal input (dentate gyrus) and output (CA1/CA3) regions is uncoupled. To
date, the behavioural significance of dentate spikes is unknown. Here, we provide
evidence that disrupting the dentate spike-related uncoupling of the dentate
gyrus and the CA1/CA3 subregions for 1 h after training retards associative
learning. We suggest dentate spikes play a significant role in memory
consolidation. ABSTRACT: Hippocampal electrophysiological oscillations, namely
theta and ripples, have been implicated in encoding and consolidation of new
memories, respectively. According to existing literature, hippocampal dentate
spikes are prominent, short-duration (<30 ms), large-amplitude (~2-4 mV)
fluctuations in hilar local-field potentials that take place during awake
immobility and sleep. Interestingly, previous studies indicate that during
dentate spikes dentate gyrus granule cells increase their firing while firing of
CA1 pyramidal cells are suppressed, thus resulting in momentary uncoupling of the
two hippocampal subregions. To date, the behavioural significance of dentate
spikes is unknown. Here, to study the possible role of dentate spikes in
learning, we trained adult male Sprague-Dawley rats in trace eyeblink classical
conditioning. For 1 h immediately following each conditioning session, one group
of animals received hippocampal stimulation via the ventral hippocampal
commissure (vHC) contingent on dentate spikes to disrupt the uncoupling between
the dentate gyrus and the CA1 subregions. A yoked control group was stimulated
during immobility, irrespective of brain state, and another control group was not
stimulated at all. As a result, learning was impaired only in the group where vHC
stimulation was administered contingent on dentate spikes. Our results suggest
dentate spikes and/or the associated uncoupling of the dentate gyrus and the CA1
play a significant role in memory consolidation. Dentate spikes could possibly
reflect reactivation and refinement of a memory trace within the dentate gyrus
triggered by input from the entorhinal cortex.
PMID- 28426129
TI - Case review and outcomes of prenatally diagnosed amniotic sheets.
PMID- 28426130
TI - Length of stay for patients undergoing invasive electrode monitoring with
stereoelectroencephalography and subdural grids correlates positively with
increased institutional profitability.
AB - OBJECTIVE: Lowering the length of stay (LOS) is thought to potentially decrease
hospital costs and is a metric commonly used to manage capacity. Patients with
epilepsy undergoing intracranial electrode monitoring may have longer LOS because
the time to seizure is difficult to predict or control. This study investigates
the effect of economic implications of increased LOS in patients undergoing
invasive electrode monitoring for epilepsy. METHODS: We retrospectively collected
and analyzed patient data for 76 patients who underwent invasive monitoring with
either subdural grid (SDG) implantation or stereoelectroencephalography (SEEG)
over 2 years at our institution. Data points collected included invasive
electrode type, LOS, profit margin, contribution margins, insurance type, and
complication rates. RESULTS: LOS correlated positively with both profit and
contribution margins, meaning that as LOS increased, both the profit and
contribution margins rose, and there was a low rate of complications in this
patient group. This relationship was seen across a variety of insurance
providers. SIGNIFICANCE: These data suggest that LOS may not be the best metric
to assess invasive monitoring patients (i.e., SEEG or SDG), and increased LOS
does not necessarily equate with lower or negative institutional financial gain.
Further research into LOS should focus on specific specialties, as each may
differ in terms of financial implications.
PMID- 28426131
TI - Sonographic appearance of proliferative fasciitis---A case report.
AB - Proliferative fasciitis is a benign entity involving the subcutaneous tissues and
fascias, characterized by the proliferation of fibroblast-like spindle cells and
ganglion-like cells. However, proliferative fasciitis may be easily confused with
sarcoma clinically and pathologically, because it appears as a rapidly growing
painful mass and has histologic features such as high cellularity, bizarre
morphologic patterns, mitotic figures, and diffuse infiltrative proliferation.
Imaging findings of proliferative fasciitis have been very rarely reported. We
report the sonographic findings in a case of proliferative fasciitis in a 43-year
old woman with histopathological correlation. (c) 2017 Wiley Periodicals, Inc. J
Clin Ultrasound 45:445-449, 2017.
PMID- 28426132
TI - A parasitoid wasp's odd pupal vigil.
PMID- 28426133
TI - Quantitative phase microscopy spatial signatures of cancer cells.
AB - We present cytometric classification of live healthy and cancerous cells by using
the spatial morphological and textural information found in the label-free
quantitative phase images of the cells. We compare both healthy cells to primary
tumor cells and primary tumor cells to metastatic cancer cells, where tumor
biopsies and normal tissues were isolated from the same individuals. To mimic
analysis of liquid biopsies by flow cytometry, the cells were imaged while
unattached to the substrate. We used low-coherence off-axis interferometric phase
microscopy setup, which allows a single-exposure acquisition mode, and thus is
suitable for quantitative imaging of dynamic cells during flow. After
acquisition, the optical path delay maps of the cells were extracted and then
used to calculate 15 parameters derived from the cellular 3D morphology and
texture. Upon analyzing tens of cells in each group, we found high statistical
significance in the difference between the groups in most of the parameters
calculated, with the same trends for all statistically significant parameters.
Furthermore, a specially designed machine learning algorithm, implemented on the
phase map extracted features, classified the correct cell type
(healthy/cancer/metastatic) with 81-93% sensitivity and 81-99% specificity. The
quantitative phase imaging approach for liquid biopsies presented in this paper
could be the basis for advanced techniques of staging freshly isolated live
cancer cells in imaging flow cytometers. (c) 2017 International Society for
Advancement of Cytometry.
PMID- 28426134
TI - Metastasis detection from whole slide images using local features and random
forests.
AB - Digital pathology has led to a demand for automated detection of regions of
interest, such as cancerous tissue, from scanned whole slide images. With
accurate methods using image analysis and machine learning, significant speed-up,
and savings in costs through increased throughput in histological assessment
could be achieved. This article describes a machine learning approach for
detection of cancerous tissue from scanned whole slide images. Our method is
based on feature engineering and supervised learning with a random forest model.
The features extracted from the whole slide images include several local
descriptors related to image texture, spatial structure, and distribution of
nuclei. The method was evaluated in breast cancer metastasis detection from lymph
node samples. Our results show that the method detects metastatic areas with high
accuracy (AUC = 0.97-0.98 for tumor detection within whole image area, AUC = 0.84
0.91 for tumor vs. normal tissue detection) and that the method generalizes well
for images from more than one laboratory. Further, the method outputs an
interpretable classification model, enabling the linking of individual features
to differences between tissue types. (c) 2017 International Society for
Advancement of Cytometry.
PMID- 28426135
TI - TLR-Stimulated Eosinophils Mediate Recruitment and Activation of NK Cells In
Vivo.
AB - Eosinophils like many myeloid innate immune cells can provide cytokines and
chemokines for the activation of other immune cells upon TLR stimulation. When
TLR-stimulated eosinophils were inoculated i.p. into wild-type mice, and NK cells
were rapidly recruited and exhibited antitumour cytotoxicity. However, when mice
depleted of CD11c+ cells were used, a marked decrease in the number of recruited
NK cells was observed. We postulated that CpG or LPS from the injected
eosinophils could be transferred to host cells, which in turn could recruit NK
cells. However, by inoculating mice deficient in TLR4 or TLR9 with LPS or CpG
stimulated eosinophils respectively, NK cell recruitment was still observed
alongside cytotoxicity and IFNgamma production. CpG stimulation of eosinophils
produced the pro-inflammatory cytokine IL-12 and the chemokine CXCL10, which are
important for NK cell activation and recruitment in vivo. To demonstrate the
importance of CXCL10 in NK cell recruitment, we found that CpG-stimulated
eosinophils pretreated with the gut microbial metabolite butyrate had reduced
expression and production of CXCL10 and IL-12 and concomitantly were poor at
recruitment of NK cells and inducing IFNgamma in NK cells. Therefore, eosinophils
like other innate immune cells of myeloid origin can conceivably stimulate NK
cell activity. In addition, products of the gut microbiota can be potential
inhibitors of NK cell.
PMID- 28426136
TI - Differentiating signals to make biological sense - A guide through databases for
MS-based non-targeted metabolomics.
AB - Metabolite identification is one of the most challenging steps in metabolomics
studies and reflects one of the greatest bottlenecks in the entire workflow. The
success of this step determines the success of the entire research, therefore the
quality at which annotations are given requires special attention. A variety of
tools and resources are available to aid metabolite identification or annotation,
offering different and often complementary functionalities. In preparation for
this article, almost 50 databases were reviewed, from which 17 were selected for
discussion, chosen for their online ESI-MS functionality. The general
characteristics and functions of each database is discussed in turn, considering
the advantages and limitations of each along with recommendations for optimal use
of each tool, as derived from experiences encountered at the Centre for
Metabolomics and Bioanalysis (CEMBIO) in Madrid. These databases were evaluated
considering their utility in non-targeted metabolomics, including aspects such as
identifier assignment, structural assignment and interpretation of results.
PMID- 28426137
TI - Hydroxyurea (hydroxycarbamide) for sickle cell disease.
AB - BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited
diseases worldwide. It is associated with lifelong morbidity and a reduced life
expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug,
ameliorates some of the clinical problems of SCD, in particular that of pain, by
raising fetal haemoglobin. This is an update of a previously published Cochrane
Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with
SCD (all genotypes), of any age, regardless of setting. SEARCH METHODS: We
searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
Haemoglobinopathies Register, comprising of references identified from
comprehensive electronic database searches and handsearches of relevant journals
and abstract books of conference proceedings. We also searched online trial
registries.Date of the most recent search: 16 January 2017. SELECTION CRITERIA:
Randomised and quasi-randomised controlled trials, of one month or longer,
comparing hydroxyurea with placebo, standard therapy or other interventions for
people with SCD. DATA COLLECTION AND ANALYSIS: Authors independently assessed
studies for inclusion, carried out data extraction and assessed the risk of bias.
MAIN RESULTS: Seventeen studies were identified in the searches; eight randomised
controlled trials were included, recruiting 899 adults and children with SCD
(haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sbetaothalassaemia
(HbSbetaothal) genotypes). Studies lasted from six to 30 months.Four studies (577
adults and children with HbSS or HbSbetaothal) compared hydroxyurea to placebo;
three recruited individuals with only severe disease and one recruited
individuals with all disease severities. There were statistically significant
improvements in terms of pain alteration (using measures such as pain crisis
frequency, duration, intensity, hospital admissions and opoid use), measures of
fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest
syndrome and blood transfusions in the hydroxyurea groups. There were no
consistent statistically significant differences in terms of quality of life and
adverse events (including serious or life-threatening events). Seven deaths
occurred during the studies, but the rates by treatment group were not
statistically significantly different.Two studies (254 children with HbSS or
HbSbetaothal also with risk of primary or secondary stroke) compared hydroxyurea
and phlebotomy to transfusion and chelation; there were statistically significant
improvements in terms of measures of fetal haemoglobin and neutrophil counts, but
more occurrences of acute chest syndrome and infections in the hydroxyurea and
phlebotomy group. There were no consistent statistically significant differences
in terms of pain alteration and adverse events (including serious or life
threatening events). Two deaths occurred during the studies (one in a the
hydroxyurea treatment arm and one in the control arm), but the rates by treatment
group were not statistically significantly different. In the primary prevention
study, no strokes occurred in either treatment group but in the secondary
prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group
(none in the transfusion and chelation group) and the study was terminated
early.The quality of the evidence for the above two comparisons was judged as
moderate to low as the studies contributing to these comparisons were mostly
large and well designed (and at low risk of bias); however evidence was limited
and imprecise for some outcomes such as quality of life, deaths during the
studies and adverse events and results are applicable only to individuals with
HbSS and HbSbetaothal genotypes.Of the remaining two studies, one (22 children
with HbSS or HbSbetaothal also at risk of stoke) compared hydroxyurea to
observation; there were statistically significant improvements in terms of
measures of fetal haemoglobin and neutrophil counts but no statistically
significant differences in terms of adverse events (including serious or life
threatening events).The final study (44 adults and children with HbSC) compared
treatment regimens with and without hydroxyurea - there was statistically
significant improvement in terms of measures of fetal haemoglobin, but no
statistically significant differences in terms of adverse events (including
serious or life-threatening events). No participants died in either of these
studies and other outcomes relevant to the review were not reported.The quality
of the evidence for the above two comparisons was judged to be very low due to
the limited number of participants, the lack of statistical power (as both
studies were terminated early with approximately only 20% of their target sample
size recruited) and the lack of applicability to all age groups and genotypes.
AUTHORS' CONCLUSIONS: There is evidence to suggest that hydroxyurea is effective
in decreasing the frequency of pain episodes and other acute complications in
adults and children with sickle cell anaemia of HbSS or HbSbetaothal genotypes
and in preventing life-threatening neurological events in those with sickle cell
anaemia at risk of primary stroke by maintaining transcranial doppler velocities.
However, there is still insufficient evidence on the long-term benefits of
hydroxyurea, particularly in preventing chronic complications of SCD,
recommending a standard dose or dose escalation to maximum tolerated dose. There
is also insufficient evidence about the long-term risks of hydroxyurea, including
its effects on fertility and reproduction. Evidence is also limited on the
effects of hydroxyurea on individuals with HbSC genotype. Future studies should
be designed to address such uncertainties.
PMID- 28426138
TI - Incremental burden of cardiovascular comorbidity and psoriatic arthritis among
adults with moderate-to-severe psoriasis in five European countries.
AB - BACKGROUND: Moderate-to-severe psoriasis is associated with reduced health
related quality of life (HRQoL). Individuals with psoriasis are at increased risk
for other medical conditions, but little information quantifies the incremental
burden of psoriasis-associated comorbidity among European adults, and data have
generally been limited to clinical samples. OBJECTIVE: To quantify the
incremental burden of cardiovascular comorbidity and psoriatic arthritis among
adults with moderate-to-severe psoriasis in the general population of France,
Germany, Italy, Spain and the United Kingdom (EU5). METHODS: All measures were
self-reported and came from the 2010-2013 EU5 National Health and Wellness
Surveys (NHWS). Moderate-to-severe psoriasis was identified by >10% body surface
area affected by psoriasis and/or use of therapies for moderate-severe disease.
Outcomes were SF-12v2/SF-36v2 mental and physical component summary scores (MCS
and PCS, respectively), SF-6D health utility, Work Productivity and Activity
Impairment (WPAI) questionnaire and healthcare use in the past 6 months.
Generalized linear models compared across cardiovascular comorbidity (CV) or
psoriatic arthritis (PsA) groups vs. non-CV or non-PsA groups with appropriate
link functions to adjust for covariates. RESULTS: Among moderate-to-severe
psoriasis respondents (n = 957), 19.8% (n = 190) reported CV comorbidity and
12.3% (n = 118) reported PsA. After adjustment for covariates, CV comorbidity was
associated with 3.0 points lower MCS, 3.4 points lower PCS and 0.05 points lower
SF-6D (all P < 0.01). Likewise, they had greater mean work impairment (48% vs.
33%), more activity impairment (48% vs. 37%), and more healthcare provider visits
(8.8 vs. 6.9), emergency room visits (0.65 vs. 0.31) and hospitalizations (0.61
vs. 0.22) (all P < 0.05). Compared to non-PsA respondents, PsA respondents also
had worse mean MCS (2.6 points), PCS (6.3 points) and SF-6D scores (0.07 points),
and more work impairment (52% vs. 34%), activity impairment (54% vs. 38%) and
healthcare provider visits (10.5 vs. 6.9) (all P < 0.05). CONCLUSION: CV
comorbidity and PsA were associated with significant incremental burden among EU5
adults with moderate-to-severe psoriasis.
PMID- 28426139
TI - Engineering a Promiscuous Tautomerase into a More Efficient Aldolase for Self
Condensations of Linear Aliphatic Aldehydes.
AB - The enzyme 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 takes
part in a catabolic pathway for aromatic hydrocarbons, where it catalyzes the
conversion of 2hydroxyhexa-2,4-dienedioate into 2-oxohexa-3-enedioate. This
tautomerase can also promiscuously catalyze carbon-carbon bond-forming reactions,
including various types of aldol reactions, by using its amino-terminal proline
as a key catalytic residue. Here, we used systematic mutagenesis to identify two
hotspots in 4-OT (Met45 and Phe50) at which single mutations give marked
improvements in aldolase activity for the self-condensation of propanal. Activity
screening of a focused library in which these two hotspots were varied led to the
discovery of a 4-OT variant (M45Y/F50V) with strongly enhanced aldolase activity
in the self-condensation of linear aliphatic aldehydes, such as acetaldehyde,
propanal, and butanal, to yield alpha,beta-unsaturated aldehydes. With both
propanal and benzaldehyde, this double mutant, unlike the previously constructed
single mutant F50A, mainly catalyzes the self-condensation of propanal rather
than the cross-condensation of propanal and benzaldehyde, thus indicating that it
indeed has altered substrate specificity. This variant could serve as a template
to create new biocatalysts that lack dehydration activity and possess further
enhanced aldolase activity, thus enabling the efficient enzymatic self-coupling
of aliphatic aldehydes.
PMID- 28426140
TI - Stomatal kinetics and photosynthetic gas exchange along a continuum of isohydric
to anisohydric regulation of plant water status.
AB - Species' differences in the stringency of stomatal control of plant water
potential represent a continuum of isohydric to anisohydric behaviours. However,
little is known about how quasi-steady-state stomatal regulation of water
potential may relate to dynamic behaviour of stomata and photosynthetic gas
exchange in species operating at different positions along this continuum. Here,
we evaluated kinetics of light-induced stomatal opening, activation of
photosynthesis and features of quasi-steady-state photosynthetic gas exchange in
10 woody species selected to represent different degrees of anisohydry. Based on
a previously developed proxy for the degree of anisohydry, species' leaf water
potentials at turgor loss, we found consistent trends in photosynthetic gas
exchange traits across a spectrum of isohydry to anisohydry. More anisohydric
species had faster kinetics of stomatal opening and activation of photosynthesis,
and these kinetics were closely coordinated within species. Quasi-steady-state
stomatal conductance and measures of photosynthetic capacity and performance were
also greater in more anisohydric species. Intrinsic water-use efficiency
estimated from leaf gas exchange and stable carbon isotope ratios was lowest in
the most anisohydric species. In comparisons between gas exchange traits, species
rankings were highly consistent, leading to species-independent scaling
relationships over the range of isohydry to anisohydry observed.
PMID- 28426141
TI - Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8+ T
Cytotoxic Lymphocytes and CD19+ B Lymphocytes in Rheumatoid Arthritis Responding
to TNF-alpha Inhibition.
AB - Melanocortin signalling in leucocyte subsets elicits anti-inflammatory and immune
tolerance inducing effects in animal experimental inflammation. In man, however,
the effects of melanocortin signalling in inflammatory conditions have scarcely
been examined. We explored the differential reactions of melanocortin 1-5
receptors (MC1-5R) gene expressions in pathogenetic leucocyte subsets in
rheumatoid arthritis (RA) to treatment with TNF-alpha inhibitor adalimumab. Seven
patients with active RA donated blood at start and at 3-month treatment. CD4+ T
helper (h) lymphocytes (ly), CD8+ T cytotoxic (c) ly, CD19+ B ly and CD14+
monocytes were isolated, using immunomagnetic beads, total RNA extracted and
reverse transcription quantitative polymerase chain reaction (RT-qPCR) performed.
Fold changes in MC1-5R, Th1-, inflammatory- and regulatory cytokine gene
expressions were assessed for correlation. Six patients responded to adalimumab
treatment, while one patient was non-responder. In all lymphocyte subtypes, MC1
5R gene expressions decreased in responders and increased in the non-responder.
In responders, decrease in MC2R, MC3R and MC4R gene expressions in CD8+ Tc and
CD19+ B ly was significant. Fold change in MC1-5R and IFNgamma gene expressions
correlated significantly in CD8+ Tc ly, while fold change in MC1R, MC3R and MC5R
and IL-1beta gene expressions correlated significantly in CD4+ Th ly. Our results
show regulation of MC2R, MC3R and MC4R gene expressions in CD8+ Tc ly and CD19+ B
ly. The correlations between fold change in different MCRs and disease driving
cytokine gene expressions in CD8+ Tc ly and CD4+ Th ly point at a central immune
modulating function of the melanocortin system in RA.
PMID- 28426142
TI - Integrated care in cancer: What is it, how is it used and where are the gaps? A
textual narrative literature synthesis.
AB - Integrated care is an underpinning concept of contemporary health care policy
proffered as a strategy to overcome the fragmentations in care encountered by
people with complex care needs (Shaw et al. [2011] What is Integrated Care? An
Overview of Integrated Care in the NHS). Cancer patients have potential to
benefit from such policy, often having needs that extend beyond cancer. This
paper seeks to understand how the concept of integrated care is used in the
cancer literature. A search of leading databases was conducted for original
research relating to integrated care or an integration intervention aiming to
improve outcomes of cancer patients, and analysed using textual narrative
synthesis. 38 papers were included, each with a focus on improving cancer
specific aspects of care enhancing the capabilities of the cancer
multidisciplinary team. Of the eight studies involving integration between the
cancer service and other care providers, all focused on utilising the external
provider to deliver aspects of cancer care or placed them in a passive role, as
survey participant, a recipient of cancer-related clinical information or as the
comparator "usual care" arm. Within the cancer literature, integration is
predominantly used to describe initiatives to improve cancer-related aspects of
care. Less attention is given to integration initiatives that enhance
coordination across levels of the healthcare system or service providers.
PMID- 28426143
TI - Coronal Transcranial Sonography and M-Mode Tremor Frequency Determination in
Parkinson's Disease and Essential Tremor.
AB - BACKGROUND AND PURPOSE: The axial mesencephalic transcranial sonography plane is
an established and sensitive diagnostic tool for the differentiation of
Parkinson's disease and essential tremor. However, the substantia nigra can also
be depicted in a second coronal examination plane, whose diagnostic value has not
yet been evaluated. Furthermore, the M-mode tremor frequency determination
represents another sonographic tool, which might yield additional diagnostic
value. METHODS: We included patients with diagnosed Parkinson's disease (n = 31),
essential tremor (n = 16), and healthy age-matched controls (n = 16). All were
examined by transcranial sonography in the axial and coronal plane. Tremor
frequencies were quantified by an M-mode tremor frequency determination
examination protocol. A clinical assessment was conducted in all participants.
RESULTS: The utilization of a coronal examination plane improved the diagnostic
strength in discriminating of Parkinson's disease from essential tremor and
healthy controls. In combination with the determination of tremor frequency, best
discriminative results were achieved (sensitivity, 90.3%; specificity, 96.9%). In
the Parkinson's disease group, we found a significant positive correlation
between hyposmia and coronal hyperechogenicity. CONCLUSION: The combined usage of
coronal transcranial sonography and M-mode tremor frequency determination should
be considered to improve diagnostic strength of sonographic techniques for the
diagnosis of Parkinson's disease.
PMID- 28426144
TI - A multiplex culture system for the long-term growth of fission yeast cells.
AB - Maintenance of long-term cultures of yeast cells is central to a broad range of
investigations, from metabolic studies to laboratory evolution assays. However,
repeated dilutions of batch cultures lead to variations in medium composition,
with implications for cell physiology. In Saccharomyces cerevisiae, powerful
miniaturized chemostat setups, or ministat arrays, have been shown to allow for
constant dilution of multiple independent cultures. Here we set out to adapt
these arrays for continuous culture of a morphologically and physiologically
distinct yeast, the fission yeast Schizosaccharomyces pombe, with the goal of
maintaining constant population density over time. First, we demonstrated that
the original ministats are incompatible with growing fission yeast for more than
a few generations, prompting us to modify different aspects of the system design.
Next, we identified critical parameters for sustaining unbiased vegetative growth
in these conditions. This requires deletion of the gsf2 flocculin-encoding gene,
along with addition of galactose to the medium and lowering of the culture
temperature. Importantly, we improved the flexibility of the ministats by
developing a piezo-pump module for the independent regulation of the dilution
rate of each culture. This made it possible to easily grow strains that have
different generation times in the same assay. Our system therefore allows for
maintaining multiple fission yeast cultures in exponential growth, adapting the
dilution of each culture over time to keep constant population density for
hundreds of generations. These multiplex culture systems open the door to a new
range of long-term experiments using this model organism. (c) 2017 The Authors.
Yeast published by John Wiley & Sons, Ltd.
PMID- 28426145
TI - Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria
Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent
Infection.
AB - To screen effective antigens as therapeutic subunit vaccines against
Mycobacterium latent infection, we did bioinformatics analysis and literature
review to identify effective antigens and evaluated the immunogenicity of five
antigens highly expressed in dormant bacteria, which included Rv2031c (HspX),
Rv2626c (Hrp1), Rv2007c (FdxA), Rv1738 and Rv3130c. Then, several fusion proteins
such as Rv2007c-Rv2626c (F6), Rv2031c-Rv1738-Rv1733c (H83), ESAT6-Rv1738-Rv2626c
(LT40), ESAT6-Ag85B-MPT64<190-198> -Mtb8.4 (EAMM), and EAMM-Rv2626c (LT70) were
constructed and their therapeutic effects were evaluated in pulmonary
Mycobacterium bovis Bacilli Calmette-Guerin (BCG) - latently infected rabbit or
mouse models. The results showed that EAMM and F6 plus H83 had therapeutic effect
against BCG latent infection in the rabbit model, respectively, and that the
combination of EAMM with F6 plus H83 significantly reduced the bacterial load. In
addition, the fusion proteins LT40 and LT70 consisting of multistage antigens
showed promising therapeutic effects in the mouse model. We conclude that subunit
vaccines consisting of both latency and replicating-associated antigens show
promising therapeutic effects in BCG latent infection animal models.
PMID- 28426146
TI - The influence of substance use on depressive symptoms among young adult black
men: The sensitizing effect of early adversity.
AB - BACKGROUND AND OBJECTIVES: Depressive symptoms have been identified as an
important consequence of substance use. Both heavy drinking and marijuana use
have acute and short-term effects on systems that regulate emotion, increasing
the potential for substance use to induce problems with negative affect and
irritability. We investigated the effects of alcohol and marijuana use on
depressive symptoms among a sample of young Black men. We also tested the stress
sensitization hypothesis that exposure to adverse childhood experiences would
amplify the influence of substance use on men's depressive symptoms. METHODS:
Hypotheses were tested with 505 rural Black men who, at ages 19-22 years,
provided data on their substance use, adverse childhood experiences, and
depressive symptoms; they provided data again 18 months later. RESULTS: Substance
use forecasted increases in depressive symptoms; cross-lagged analyses yielded no
evidence for the inverse path, depressive symptoms increasing substance use. The
impact of substance use on depressive symptoms was amplified among young Black
men who were exposed to adverse childhood experiences. Substance use did not
significantly predict depressive symptoms when adversity was low. DISCUSSION AND
CONCLUSIONS: Our findings suggest that, during young adulthood, substance use
increases depressive symptoms among Black men who were exposed to childhood
adversity. Because childhood adversity disproportionately affects Black men,
these findings inform future cross-group research designed to investigate racial
disparities in the consequences of substance use. SCIENTIFIC SIGNIFICANCE:
Depressive symptoms may be understood as an effect as well as a cause of
substance use, particularly among vulnerable young Black men. (Am J Addict
2017;26:400-406).
PMID- 28426147
TI - Propagation of error from parameter constraints in quantitative MRI: Example
application of multiple spin echo T2 mapping.
AB - PURPOSE: Quantitative MRI may require correcting for nuisance parameters which
can or must be constrained to independently measured or assumed values. The noise
and/or bias in these constraints propagate to fitted parameters. For example, the
case of refocusing pulse flip angle constraint in multiple spin echo T2 mapping
is explored. METHODS: An analytical expression for the mean-squared error of a
parameter of interest was derived as a function of the accuracy and precision of
an independent estimate of a nuisance parameter. The expression was validated by
simulations and then used to evaluate the effects of flip angle (theta)
constraint on the accuracy and precision of T?2 for a variety of multi-echo T2
mapping protocols. RESULTS: Constraining theta improved T?2 precision when the
theta-map signal-to-noise ratio was greater than approximately one-half that of
the first spin echo image. For many practical scenarios, constrained fitting was
calculated to reduce not just the variance but the full mean-squared error of
T?2, for bias in theta??6%. CONCLUSION: The analytical expression derived in this
work can be applied to inform experimental design in quantitative MRI. The
example application to T2 mapping provided specific cases, depending on theta?
accuracy and precision, in which theta? measurement and constraint would be
beneficial to T?2 variance or mean-squared error. Magn Reson Med 79:673-682,
2018. (c) 2017 International Society for Magnetic Resonance in Medicine.
PMID- 28426148
TI - Three-dimensional finite-element based deformable image registration for
evaluation of pleural cavity irradiation during photodynamic therapy.
AB - PURPOSE: Photodynamic therapy (PDT) is used after surgical resection to treat the
microscopic disease for malignant pleural mesothelioma and to increase survival
rates. As accurate light delivery is imperative to PDT efficacy, the deformation
of the pleural volume during the surgery is studied on its impact on the
delivered light fluence. In this study, a three-dimensional finite element-based
(3D FEM) deformable image registration is proposed to directly match the volume
of lung to the volume of pleural cavity obtained during PDT to have accurate
representation of the light fluence accumulated in the lung, heart and liver
(organs-at-risk) during treatment. METHODS: A wand, comprised of a modified
endotrachial tube filled with Intralipid and an optical fiber inside the tube, is
used to deliver the treatment light. The position of the treatment is tracked
using an optical tracking system with an attachment comprised of nine reflective
passive markers that are seen by an infrared camera-based navigation system. This
information is used to obtain the surface contours of the plural cavity and the
cumulative light fluence on every point of the cavity surface that is being
treated. The lung, heart, and liver geometry are also reconstructed from a series
of computed tomography (CT) scans of the organs acquired in the same patient
before and after the surgery. The contours obtained with the optical tracking
system and CTs are imported into COMSOL Multiphysics, where the 3D FEM-based
deformable image registration is obtained. The delivered fluence values are
assigned to the respective positions (x, y, and z) on the optical tracking
contour. The optical tracking contour is considered as the reference, and the CT
contours are used as the target, which will be deformed. The data from three
patients formed the basis for this study. RESULTS: The physical correspondence
between the CT and optical tracking geometries, taken at different times, from
different imaging devices was established using the 3D FEM-based image deformable
registration. The volume of lung was matched to the volume of pleural cavity and
the distribution of light fluence on the surface of the heart, liver and deformed
lung volumes was obtained. CONCLUSION: The method used is appropriate for
analyzing problems over complicated domains, such as when the domain changes (as
in a solid-state reaction with a moving boundary), when the desired precision
varies over the entire domain, or when the solution lacks smoothness.
Implementing this method in real-time for clinical applications and in situ
monitoring of the under- or over- exposed regions to light during PDT can
significantly improve the treatment for mesothelioma.
PMID- 28426149
TI - Click-Chemistry-Mediated Rapid Microbubble Capture for Acute Thrombus Ultrasound
Molecular Imaging.
AB - Bioorthogonal coupling chemistry has been studied as a potentially advantageous
approach for molecular imaging because it offers rapid, efficient, and strong
binding, which might also benefit stability, production, and chemical
conjugation. The inverse-electron-demand Diels-Alder reaction between a 1,2,4,5
tetrazine and trans-cyclooctene (TCO) is an example of a highly selective and
rapid bioorthogonal coupling reaction that has been used successfully to prepare
targeted molecular imaging probes. Here we report a fast, reliable, and highly
sensitive approach, based on a two-step pretargeting bioorthogonal approach, to
achieving activated-platelet-specific CD62p-targeted thrombus ultrasound
molecular imaging. Tetrazine-modified microbubbles (tetra-MBs) could be uniquely
and rapidly captured by subsequent click chemistry of thrombus tagged with a
trans-cyclooctene-pretreated CD62p antibody. Moreover, such tetra-MBs showed
great long-term stability under physiological conditions, thus offering the
ability to monitor thrombus changes in real time. We demonstrated for the first
time that a bioorthogonal targeting molecular ultrasound imaging strategy based
on tetra-MBs could be a simple but powerful tool for rapid diagnosis of acute
thrombosis.
PMID- 28426150
TI - Measurements of morphological and biophysical alterations in individual neuron
cells associated with early neurotoxic effects in Parkinson's disease.
AB - Parkinson's disease (PD) is a common neurodegenerative disease. However,
therapeutic methods of PD are still limited due to complex pathophysiology in PD.
Here, optical measurements of individual neurons from in vitro PD model using
optical diffraction tomography (ODT) are presented. By measuring 3D refractive
index distribution of neurons, morphological and biophysical alterations in in
vitro PD model are quantitatively investigated. It was found that neurons show
apoptotic features in early PD progression. The present approach will open up new
opportunities for quantitative investigation of the pathophysiology of various
neurodegenerative diseases. (c) 2017 International Society for Advancement of
Cytometry.
PMID- 28426151
TI - Ammonothermal Synthesis of Earth-Abundant Nitride Semiconductors ZnSiN2 and
ZnGeN2 and Dissolution Monitoring by In Situ X-ray Imaging.
AB - In this contribution, first synthesis of semiconducting ZnSiN2 and ZnGeN2 from
solution is reported with supercritical ammonia as solvent and KNH2 as
ammonobasic mineralizer. The reactions were conducted in custom-built high
pressure autoclaves made of nickel-based superalloy. The nitrides were
characterized by powder X-ray diffraction and their crystal structures were
refined by the Rietveld method. ZnSiN2 (a=5.24637(4), b=6.28025(5), c=5.02228(4)
A, Z=4, Rwp =0.0556) and isotypic ZnGeN2 (a=5.46677(10), b=6.44640(12),
c=5.19080(10) A, Z=4, Rwp =0.0494) crystallize in the orthorhombic space group
Pna21 (no. 33). The morphology and elemental composition of the nitrides were
examined by electron microscopy and energy-dispersive X-ray spectroscopy (EDX).
Well-defined single crystals with a diameter up to 7 MUm were grown by
ammonothermal synthesis at temperatures between 870 and 1070 K and pressures up
to 230 MPa. Optical properties have been analyzed with diffuse reflectance
measurements. The band gaps of ZnSiN2 and ZnGeN2 were determined to be 3.7 and
3.2 eV at room temperature, respectively. In situ X-ray measurements were
performed to exemplarily investigate the crystallization mechanism of ZnGeN2 .
Dissolution in ammonobasic supercritical ammonia between 570 and 670 K was
observed which is quite promising for the crystal growth of ternary nitrides
under ammonothermal conditions.
PMID- 28426152
TI - Donor-specific alloreactive T cells can be quantified from whole blood, and may
predict cellular rejection after renal transplantation.
AB - Preformed cellular alloreactivity can exist prior to transplantation and may
contribute to rejection. Here, we used a rapid flow-cytometric whole-blood assay
to characterize the extent of alloreactive T cells among 1491 stimulatory
reactions from 61 renal transplant candidates and 75 controls. The role of
preformed donor-specific alloreactive T cells in cellular rejection was
prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8+ T
cells were more frequent than respective CD4+ T cells, and these levels were
stable over time. CD8+ T cells were effector-memory T cells largely negative for
expression of CD27, CD62L, and CCR7, and were susceptible to steroid and
calcineurin inhibitor inhibition. Alloreactivity was more frequent in samples
with higher number of HLA mismatches. Moreover, the percentage of individuals
with alloreactive T cells was higher in transplant candidates than in controls.
Among transplant candidates, 5/61 exhibited alloreactive CD8+ T cells against
most stimulators, 23/61 toward a limited number of stimulators, and 33/61 did not
show any alloreactivity. Among 21 renal transplant recipients followed
prospectively, one had donor-specific preformed T-cell alloreactivity. She was
the only patient who developed cellular rejection posttransplantation. In
conclusion, donor-specific alloreactive T cells may be rapidly quantified from
whole blood, and may predict cellular rejection after transplantation.
PMID- 28426153
TI - A Non-pathogenic Recombinant Leishmania Expressing Lipophosphoglycan 3 Against
Experimental Infection with Leishmania infantum.
AB - Visceral leishmaniasis (VL) is caused by Leishmania infantum in the Mediterranean
basin and affects primarily children and immunosuppressed individuals. Various
strategies of vaccination have so far been examined by either protein or DNA
without achievable complete protection against the disease. The live non
pathogenic lizard parasite, Leishmania tarentolae, expressing elected Leishmania
antigens has recently provided a promising new approach as a safe and effective
live vaccine candidate to prevent leishmaniasis. Here, we evaluated the
immunoprotective potential of a live recombinant L. tarentolae expressing
Lipophosphoglycan 3 (LPG3) antigen against L. infantum infection in BALB/c mice.
Results indicated that the administration of live recombinant Leishmania produced
a significant high level of IFN-gamma accompanied by reduced levels of IL-10 as
compared to wild-type parasites as live vaccine control, thus suggesting the
induction of a Th1-type immune response in a mouse model of visceral
leishmaniasis. Analysis of the IgG antibody response also showed high levels of
IgG2a relative to IgG1 in sera of mice immunized with recombinant Leishmania
parasites. However, immune responses elicited by this live vaccine conferred
partial protection against infectious challenge. Therefore, further studies are
required to increase its protective efficacy.
PMID- 28426154
TI - Transparent and Gas-Permeable Liquid Marbles for Culturing and Drug Sensitivity
Test of Tumor Spheroids.
AB - Transparent nanoparticle-based liquid marbles with high gas-permeability are
prepared to culture tumor spheroids in 3D without the need of supplementary
growth factor. The culturing process of spheroids from a population of cancer
cells or a single cell in the transparent liquid marbles can be optically
recorded continuously. Compared to monolayer cells and spheroids generated in
multiwell plate, tumor spheroids cultured in the liquid marbles show enhanced
viability under the treatment of chemotherapeutic drugs and small interfering
RNA.
PMID- 28426155
TI - Insect transmission of plant viruses: Multilayered interactions optimize viral
propagation.
AB - By serving as vectors of transmission, insects play a key role in the infection
cycle of many plant viruses. Viruses use sophisticated transmission strategies to
overcome the spatial barrier separating plants and the impediment imposed by the
plant cell wall. Interactions among insect vectors, viruses, and host plants
mediate transmission by integrating all organizational levels, from molecules to
populations. Best-examined on the molecular scale are two basic transmission
modes wherein virus-vector interactions have been well characterized. Whereas
association of virus particles with specific sites in the vector's mouthparts or
in alimentary tract regions immediately posterior to them is required for
noncirculative transmission, the cycle of particles through the vector body is
necessary for circulative transmission. Virus transmission is also determined by
interactions that are associated with changes in vector feeding behaviors and
with alterations in plant host's morphology and/or metabolism that favor the
attraction or deterrence of vectors. A recent concept in virus-host-vector
interactions proposes that when vectors land on infected plants, vector elicitors
and effectors "inform" the plants of the confluence of interacting entities and
trigger signaling pathways and plant defenses. Simultaneously, the plant
responses may also influence virus acquisition and inoculation by vectors.
Overall, a picture is emerging where transmission depends on multilayered virus
vector-host interactions that define the route of a virus through the vector, and
on the manipulation of the host and the vector. These interactions guarantee
virus propagation until one or more of the interactants undergo changes through
evolution or are halted by environmental interventions.
PMID- 28426156
TI - Natural terpene derivatives as new structural task-specific ionic liquids to
enhance the enantiorecognition of acidic enantiomers on teicoplanin-based
stationary phase by high-performance liquid chromatography.
AB - We present the specific cooperative effect of a semisynthetic glycopeptide
antibiotic teicoplanin and chiral ionic liquids containing the (1R,2S,5R)-(-)
menthol moiety on the chiral recognition of enantiomers of mandelic acid,
vanilmandelic acid, and phenyllactic acid. Experiments were performed
chromatographically on an Astec Chirobiotic T chiral stationary phase applying
the mobile phase with the addition of the chiral ionic liquids. The
stereoselective binding of enantiomers to teicoplanin in presence of new chiral
ionic liquids were evaluated applying thermodynamic measurements and the docking
simulations. Both the experimental and theoretical methods revealed that the
chiral recognition of enantiomers in the presence of new chiral ionic liquids was
enthalpy driven. The changes of the teicoplanin conformation occurring upon
binding of the chiral ionic liquids are responsible for the differences in the
standard changes in Gibbs energy (DeltaG0 ) values obtained for complexes formed
by the R and S enantiomers and teicoplanin. Docking simulations revealed the
steric adjustment between the chiral ionic liquids cyclohexane ring (chair
conformation) and the beta-d-glucosamine ring of teicoplanin and additionally
hydrophobic interactions between the decanoic aliphatic chain of teicoplanin and
the alkyl group of the tested salts. The obtained terpene derivatives can be
considered as "structural task-specific ionic liquids" responsible for enhancing
the chiral resolution in synergistic systems with two chiral selectors.
PMID- 28426157
TI - Effects of ambient temperature in association with photoperiod on phenology and
on the expressions of major plant developmental genes in wheat (Triticum aestivum
L.).
AB - In addition to its role in vernalization, temperature is an important
environmental stimulus in determining plant growth and development. We used
factorial combinations of two photoperiods (16H, 12H) and three temperature
levels (11, 18 and 25 degrees C) to study the temperature responses of 19 wheat
cultivars with established genetic relationships. Temperature produced more
significant effects on plant development than photoperiod, with strong genotypic
components. Wheat genotypes with PPD-D1 photoperiod sensitive allele were
sensitive to temperature; their development was delayed by higher temperature,
which intensified under non-inductive conditions. The effect of temperature on
plant development was not proportional; it influenced the stem elongation to the
largest extent, and warmer temperature lengthened the lag phase between the
detection of first node and the beginning of intensive stem elongation. The gene
expression patterns of VRN1, VRN2 and PPD1 were also significantly modified by
temperature, while VRN3 was more chronologically regulated. The associations
between VRN1 and VRN3 gene expression with early apex development were
significant in all treatments but were only significant for later plant
developmental phases under optimal conditions (16H and 18 degrees C). Under 16H,
the magnitude of the transient peak expression of VRN2 observed at 18 and 25
degrees C associated with the later developmental phases.
PMID- 28426158
TI - A novel technique for decellularization of allogenic nerves and in vivo study of
their use for peripheral nerve reconstruction.
AB - Autografts represent the gold standard for peripheral nerve reconstruction but
their limited availability, the discrepancy of nerve caliber, and long surgical
times are drawbacks. Allografts have therefore become a valid alternative option.
In particular, acellular nerve allografts (ANAs) rather than fresh allografts do
not need immunosuppression and appear to be safe and effective based on recent
studies. An innovative method was conceived to obtain ANAs, so as to speed up
nerve decellularization, without compromising nerve architecture, and without
breaking the asepsis chain. Several detergent-based techniques, integrated with
sonication and mechanical stirring, were tested in vitro on rabbit nerves, to
identify, by microscopy and immunohistochemistry, the most effective protocol in
terms of cell lysis and cellular debris clearance, while maintaining nerve
architecture. Furthermore, a pilot in vivo study was performed: ANAs were
implanted into tibial nerve defects of three rabbits, and autografts,
representing the gold standard, in other three animals. Twelve weeks
postoperatively, rabbits were clinically evaluated and euthanasized; grafts were
harvested and microscopically and histomorphometrically analyzed. The method
proved to be effective in vitro: the treatment removed axons, myelin and cells,
without altering nerve architecture. The in vivo study did not reveal any adverse
effect: animals maintained normal weight and function of posterior limb during
the entire experimental time. A mild fibrotic reaction was observed, macrophages
and leukocytes were rare or absent; ANAs regenerated fascicles and bundles were
comparable versus autografts. Based on these results, this decellularization
protocol is encouraging and deserves deeper investigations with further
preclinical and clinical studies. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
Res Part A: 105A: 2228-2240, 2017.
PMID- 28426159
TI - Open microfluidic gel electrophoresis: Rapid and low cost separation and analysis
of DNA at the nanoliter scale.
AB - Gel electrophoresis is one of the most applied and standardized tools for
separation and analysis of macromolecules and their fragments in academic
research and in industry. In this work we present a novel approach for conducting
on-demand electrophoretic separations of DNA molecules in open microfluidic (OM)
systems on planar polymer substrates. The approach combines advantages of slab
gel, capillary- and chip-based methods offering low consumable costs (<0.1$)
circumventing cost-intensive microfluidic chip fabrication, short process times
(5 min per analysis) and high sensitivity (4 ng/MUL dsDNA) combined with
reasonable resolution (17 bases). The open microfluidic separation system
comprises two opposing reservoirs of 2-4 MUL in volume, a semi-contact written
gel line acting as separation channel interconnecting the reservoirs and sample
injected into the line via non-contact droplet dispensing and thus enabling the
precise control of the injection plug and sample concentration. Evaporation is
prevented by covering aqueous structures with PCR-grade mineral oil while
maintaining surface temperature at 15 degrees C. The liquid gel line exhibits a
semi-circular cross section of adaptable width (~200-600 MUm) and height (~30-80
MUm) as well as a typical length of 15-55 mm. Layout of such liquid structures is
adaptable on-demand not requiring time consuming and repetitive fabrication
steps. The approach was successfully demonstrated by the separation of a standard
label-free DNA ladder (100-1000 bp) at 100 V/cm via in-line staining and laser
induced fluorescent end-point detection using an automated prototype.
PMID- 28426160
TI - Assessment and support during early labour for improving birth outcomes.
AB - BACKGROUND: The progress of labour in the early or latent phase is usually slow
and may include painful uterine contractions. Women may feel distressed and lose
their confidence during this phase. Support and assessment interventions have
been assessed in two previous Cochrane Reviews. This review updates and replaces
these two reviews, which have become out of date. OBJECTIVES: To investigate the
effectiveness of assessment and support interventions for women during early
labour.In order to measure the effectiveness of the interventions, we compared
the duration of labour, the rate of obstetrical interventions, and the rate of
other maternal or neonatal outcomes. SEARCH METHODS: We searched the Cochrane
Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World
Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)
(31 October 2016) and reference lists of retrieved studies. SELECTION CRITERIA:
Randomised controlled trials of any assessment or support intervention in the
latent phase of labour. We planned to include cluster-randomised trials if they
were eligible. We did not include quasi-randomised trials. DATA COLLECTION AND
ANALYSIS: Two review authors independently assessed trials for inclusion and risk
of bias, extracted data and checked them for accuracy. We resolved any
disagreement by discussion or by involving a third assessor. The quality of the
evidence was assessed using the GRADE approach. MAIN RESULTS: We included five
trials with a total of 10,421 pregnant women in this review update. The trials
were conducted in the UK, Canada and America. The trials compared interventions
in early labour versus usual care. We examined three comparisons: early labour
assessment versus immediate admission to hospital; home visits by midwives versus
usual care (telephone triage); and one-to-one structured midwifery care versus
usual care. These trials were at moderate- risk of bias mainly because blinding
women and staff to these interventions is not generally feasible. For important
outcomes we assessed evidence using GRADE; we downgraded evidence for study
design limitations, imprecision, and where we carried out meta-analysis, for
inconsistency.One trial with 209 women compared early labour assessment with
direct admission to hospital. Duration of labour from the point of hospital
admission was reduced for women in the assessment group (mean difference (MD)
5.20 hours, 95% confidence interval (CI) -7.06 to -3.34; 209 women, low-quality
evidence). There were no clear differences between groups for the number of women
undergoing caesarean section or instrumental vaginal birth (risk ratio (RR) 0.72,
95% CI 0.30 to 1.72, very low quality evidence; and, RR 0.86, 95% CI 0.58 to
1.26, very low quality evidence, respectively). Serious maternal morbidity was
not reported. Women in the early assessment group were slightly less likely to
have epidural anaesthesia (RR 0.87, 95% CI 0.78 to 0.98, low-quality evidence),
and considerably less likely to have oxytocin for labour augmentation (RR 0.57,
95% CI 0.37 to 0.86) and this group also had increased satisfaction with their
care compared with women in the immediate admission group (MD 16.00, 95% CI 7.53
to 24.47). No babies were born before admission to hospital and only one infant
had a low Apgar score at five minutes after the birth (very low quality
evidence). Admission to neonatal special care was not reported.Three studies
examined home assessment and midwifery support versus telephone triage. One trial
reported the duration of labour; home visits did not appear to have any clear
impact compared with usual care (MD 0.29 hours, 95% CI -0.14 to 0.72; 1 trial,
3474 women, low-quality evidence). There was no clear difference for the rate of
caesarean section (RR 1.05, 95% CI 0.95 to 1.17; 3 trials, 5170 women; I2 = 0%;
moderate-quality evidence) or the rate of instrumental vaginal birth (average RR
0.95, 95% CI 0.79 to 1.15; 2 trials, 4933 women; I2 = 69%; low-quality evidence).
One trial reported birth before arrival at hospital or unplanned home birth;
there was no clear difference between the groups (RR 1.33, 95% CI 0.30 to 5.95; 1
trial, 3474 women). No clear differences were identified for serious maternal
morbidity (RR 0.93, 95% CI 0.61 to 1.42; 1 trial, 3474 women; low-quality
evidence), or use of epidural (average RR 0.95, 95% CI 0.87 to 1.05; 3 trials,
5168 women; I2 = 60%; low-quality evidence). There were no clear differences for
neonatal admission to special care (average RR 0.84, 95% CI 0.50 to 1.42; 3
trials, 5170 infants; I2 = 71%; very low quality evidence), or for Apgar score
less than seven at five minutes after birth (RR 1.19, 95% CI 0.71 to 1.99; 3
trials, 5170 infants; I2 = 0%; low-quality evidence).One study, with 5002 women,
examined one-to-one structured care in early labour versus usual care. Length of
labour was not reported. There were no clear differences between groups for the
rate of caesarean section (RR 0.93, 95% CI 0.84 to 1.02; 4996 women, high-quality
evidence), or for instrumental vaginal birth (RR 0.94, 95% CI 0.82 to 1.08; 4996
women, high-quality evidence). No clear differences between groups were reported
for serious maternal morbidity (RR 1.13, 95% CI 0.84 to 1.52; 4996 women,
moderate-quality evidence). Use of epidural was similar in the two groups (RR
1.00, 95% CI 0.99 to 1.01; 4996 women, high-quality evidence). For infant
outcomes, there were no clear differences between groups (admission to neonatal
intensive care unit: RR 0.98, 95% CI 0.80 to 1.21; 4989 infants, high-quality
evidence; Apgar score less than seven at five minutes: RR 1.07, 95% CI 0.64 to
1.79; 4989 infants, moderate-quality evidence). AUTHORS' CONCLUSIONS: Assessment
and support in early labour does not have a clear impact on rate of caesarean
section or instrumental vaginal birth, or whether the baby was born before
arrival at hospital or in an unplanned home birth. However, evidence suggested
that interventions may have an impact on reducing the use of epidural
anaesthesia, labour augmentation and on increasing maternal satisfaction with
giving birth. Evidence about the effectiveness of early labour assessment versus
immediate admission was very limited and more research is needed in this area.
PMID- 28426163
TI - Lipid Flip-Flop and Pore Nucleation on Zwitterionic Bilayers are Asymmetric under
Ionic Imbalance.
AB - Lipid flip-flop and its associated transient pore formation are key thermodynamic
properties of living cell membranes. However, there is a lack of understanding of
whether ionic imbalance that exists ubiquitously across cell membranes affects
lipid flip-flop and its associated functions. Potential of mean force
calculations show that the free-energy barrier of lipid flip-flop on the
extracellular leaflet reduces with the presence of ionic imbalance, whereas the
barrier on the intracellular leaflet is generally not affected. The linear
decrease of the activation energy of lipid flip-flop on the extracellular leaflet
is consistent with the experimentally measured conductance-voltage relationship
of zwitterionic lipid bilayers. This suggests: 1) lipid flip-flop has a
directionality under physiological conditions and phospholipids accumulate at a
rate on the order of 105 um-2 h-1 on the cytoplasmic side of cell membranes; 2)
ion permeation across a lipid membrane is moderated by lipid flip-flop; 3) the
energy barrier of pore formation is aligned with the weaker leaflet that has a
lower energy of lipid flip-flop. The asymmetry of lipid flip-flop and pore
nucleation may have substantial implications for protein translocation,
signaling, enzymatic activities, vesicle fusion, and transportation of
biomolecules on cell membranes.
PMID- 28426162
TI - Motion-corrected simultaneous cardiac positron emission tomography and coronary
MR angiography with high acquisition efficiency.
AB - PURPOSE: Develop a framework for efficient free-breathing simultaneous whole
heart coronary magnetic resonance angiography (CMRA) and cardiac positron
emission tomography (PET) on a 3 Tesla PET-MR system. METHODS: An acquisition
that enables nonrigid motion correction of both CMRA and PET has been developed.
The proposed method estimates translational motion from low-resolution 2D MR
image navigators acquired at each heartbeat and 3D nonrigid respiratory motion
between different respiratory bins from the CMRA data itself. Estimated motion is
used for correcting the CMRA as well as the emission and attenuation PET data
sets to the same respiratory position. The CMRA approach was studied in 10
healthy subjects and compared for both left and right coronary arteries (LCA,
RCA) against a reference scan with diaphragmatic navigator gating and tracking.
The PET-CMRA approach was tested in 5 oncology patients with 18 F-FDG myocardial
uptake. PET images were compared against uncorrected and gated PET
reconstructions. RESULTS: For the healthy subjects, no statistically significant
differences in vessel length and sharpness (P > 0.01) were observed between the
proposed approach and the reference acquisition with navigator gating and
tracking, although data acquisition was significantly shorter. The proposed
approach improved CMRA vessel sharpness by 37.9% and 49.1% (LCA, RCA) and vessel
length by 48.0% and 36.7% (LCA, RCA) in comparison with no motion correction for
all the subjects. Motion-corrected PET images showed improved sharpness of the
myocardium compared to uncorrected reconstructions and reduced noise compared to
gated reconstructions. CONCLUSION: Feasibility of a new respiratory motion
compensated simultaneous cardiac PET-CMRA acquisition has been demonstrated. Magn
Reson Med 79:339-350, 2018. (c) 2017 The Authors Magnetic Resonance in Medicine
published by Wiley Periodicals, Inc. on behalf of International Society for
Magnetic Resonance in Medicine. This is an open access article under the terms of
the Creative Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly cited.
PMID- 28426164
TI - Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in B
cells via upregulating Bcl2L12 in patients with allergic rhinitis.
AB - BACKGROUND AND AIMS: The function of interleukin (IL)-10-producing B cells (B10
cell) is compromised in patients with allergic diseases. Protease-activated
receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate
the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.
METHODS: Peripheral blood B cells were collected from patients with allergic
rhinitis (AR). A correlation between the expression of Bcl2-like protein 12
(Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.
RESULTS: We observed that the expression of IL-10 was lower in the peripheral B
cells from patients with airway allergy. A negative correlation was identified
between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B
cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10
expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B
cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the
capability of IL-10 expression and the immunosuppressive function. Administration
of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.
CONCLUSIONS: Activation of PAR2 inhibits the expression of IL-10 in B cells,
which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes.
The data suggest that regulation of Bcl2L12 may be a novel approach in the
treatment for AR.
PMID- 28426165
TI - Hydrogen peroxide-dependent antibacterial action of Melilotus albus honey.
AB - : Honey originating from different floral sources exhibits the broad spectrum of
antibacterial activity as a result of the presence of hydrogen peroxide as well
as nonperoxide bioactive compounds. The mechanisms of antibacterial activity of
Polish melilot honey were investigated for the first time. Polish melilot honey
samples (Melilotus albus biennial = 3 and annual = 5, Melilotus officinalis = 1)
were collected directly from beekeepers and analysed for pollen profile, basic
physicochemical parameters, antioxidant capacity, radical scavenging activity,
total phenolic contents as well as antibacterial properties against pathogenic
bacteria Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae,
Salmonella spp. The physicochemical properties of melilot honey were specific for
light-coloured unifloral honey samples and were not dependent on its botanical
and geographical origin (P > 0.05). All tested honey samples exhibited inhibitory
activity (above 90%) against Gram-positive bacteria at the concentration of 12.5
25%. Above 30-50% of antibacterial activity of melilot honey was connected with
glucose oxidase enzyme action and was destroyed in the presence of catalase.
Hydrogen peroxide-dependent antibacterial activity of honey was inversely
correlated with its radical scavenging activity (r = -0.67) and phenolic
compounds (r = -0.61). Antibacterial action of melilot honey depends not only on
hydrogen peroxide produced by glucose oxidase, but also on other nonperoxide
bioactive components of honey. SIGNIFICANCE AND IMPACT OF THE STUDY: Melilot
honey is used in traditional medicine as an anticoagulant agent due to the
possibility of the presence of the coumarin compounds which are specific for
Melilotus plant. Melilotus albus is rarely used to produce honey, and
antibacterial properties of this variety of honey had not been studied yet. Nine
samples of melilot honey produced in different regions of Poland were analysed
according to their antibacterial activity which was correlated with
physiochemical parameters and antioxidant activity. It was shown that
antibacterial activity of melilot honey is created by hydrogen peroxide and other
bioactive compounds.
PMID- 28426166
TI - Acute effects of radiofrequency electromagnetic field emitted by mobile phone on
brain function.
AB - Due to its attributes, characteristics, and technological resources, the mobile
phone (MP) has become one of the most commonly used communication devices.
Historically, ample evidence has ruled out the substantial short-term impact of
radiofrequency electromagnetic field (RF-EMF) emitted by MP on human cognitive
performance. However, more recent evidence suggests potential harmful effects
associated with MP EMF exposure. The aim of this review is to readdress the
question of whether the effect of MP EMF exposure on brain function should be
reopened. We strengthen our argument focusing on recent neuroimaging and
electroencephalography studies, in order to present a more specific analysis of
effects of MP EMF exposure on neurocognitive function. Several studies indicate
an increase in cortical excitability and/or efficiency with EMF exposure, which
appears to be more prominent in fronto-temporal regions and has been associated
with faster reaction time. Cortical excitability might also underpin disruption
to sleep. However, several inconsistent findings exist, and conclusions regarding
adverse effects of EMF exposure are currently limited. It also should be noted
that the crucial scientific question of the effect of longer-term MP EMF exposure
on brain function remains unanswered and essentially unaddressed.
Bioelectromagnetics. 38:329-338, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28426167
TI - Characterization the carotenoid productions and profiles of three Rhodosporidium
toruloides mutants from Agrobacterium tumefaciens-mediated transformation.
AB - The red yeast Rhodosporidium toruloides is a known lipid producer capable of
accumulating large amounts of triacylglycerols and carotenoids. However, it
remains challenging to study its carotenoid production profiles owing to limited
biochemical information and inefficient genetic tools. Here we used an
Agrobacterium tumefaciens-mediated transformation (ATMT) to change its carotenoid
production and profiles. We constructed R. toruloides NP11 mutant libraries with
ATMT, selected three mutants with different colours, characterized their
carotenoid products by high-pressure liquid chromatography-mass spectrometry
(HPLC-MS) analysis and assured differences among those strains in terms of
carotenoid production and its composition profiles. We then located T-DNA
insertion sites using the genome walking technology and provided discussions in
terms of the new phenotypes. This study is the first of its kind to change the
carotenoid production profiles in R. toruloides. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28426168
TI - Walking a Fine Line with Sucrose Phosphorylase: Efficient Single-Step
Biocatalytic Production of l-Ascorbic Acid 2-Glucoside from Sucrose.
AB - The 2-O-alpha-d-glucoside of l-ascorbic acid (AA-2G) is a highly stabilized form
of vitamin C, with important industrial applications in cosmetics, food, and
pharmaceuticals. AA-2G is currently produced through biocatalytic glucosylation
of l-ascorbic acid from starch-derived oligosaccharides. Sucrose would be an
ideal substrate for AA-2G synthesis, but it lacks a suitable transglycosidase. We
show here that in a narrow pH window (pH 4.8-6.0, with sharp optimum at pH 5.2),
sucrose phosphorylases catalyzed the 2-O-alpha-glucosylation of l-ascorbic acid
from sucrose with high efficiency and perfect site-selectivity. Optimized
synthesis with the enzyme from Bifidobacterium longum at 40 degrees C gave a
concentrated product (155 g L-1 ; 460 mm), from which pure AA-2G was readily
recovered in ~50 % overall yield, thus providing the basis for advanced
production. The peculiar pH dependence is suggested to arise from a "reverse
protonation" mechanism in which the catalytic base Glu232 on the glucosyl-enzyme
intermediate must be protonated for attack on the anomeric carbon from the 2
hydroxyl of the ionized l-ascorbate substrate.
PMID- 28426169
TI - Microsecond Dynamics in Ubiquitin Probed by Solid-State 15 N NMR Spectroscopy
R1rho Relaxation Experiments under Fast MAS (60-110 kHz).
AB - 15 N R1rho relaxation experiments in solid-state NMR spectroscopy are sensitive
to timescales and amplitudes of internal protein motions in the hundreds of nano-
to microsecond time window, which is difficult to probe by solution-state NMR
spectroscopy. By using 15 N R1rho relaxation experiments, a simplified approach
to detect low microsecond protein dynamics is described and residue-specific
correlation times are determined from the ratio of 15 N R1rho rate constants at
different magic angle spinning frequencies. Microcrystalline ubiquitin exhibits
small-amplitude dynamics on a timescale of about 1 MUs across the entire protein,
and larger amplitude motions, also on the 1 MUs timescale, for several sites,
including the beta1 -beta2 turn and the N terminus of the alpha helix. According
to the analysis, the microsecond protein backbone dynamics are of lower amplitude
than that concluded in previous solid-state NMR spectroscopy studies, but persist
across the entire protein with a rather uniform timescale of 1 MUs.
PMID- 28426170
TI - Detecting cancer in primary care: Where does early diagnosis stop and
overdiagnosis begin?
PMID- 28426171
TI - Sputum basophils are increased in eosinophilic asthma compared with non
eosinophilic asthma phenotypes.
AB - Sputum basophil numbers are increased in allergic asthmatics, but it is unclear
what role airway basophils play in "TH2-low" asthma phenotypes. Using flow
cytometry, we found that basophils were significantly increased in all asthmatics
(n=26) compared with healthy controls (n=8) (P=0.007) with highest levels
observed in eosinophilic asthma (EA); median 0.22%, IQR 0.11%-0.47%; n=14)
compared with non-EA (NEA) (0.06%, 0.00%-0.20%; n=12; P<0.05). In asthmatics,
basophils were positively correlated with sputum eosinophils (r=0.54; P<0.005)
and inversely with sputum neutrophils (r=-0.46: P<0.05), but not with FEV1 (%
predicted), FEV1 /FVC or bronchodilator reversibility. In a subgroup initially
identified as inadequately controlled asthma (n=7), there was a trend (P=0.08)
towards a reduction in sputum basophils following increased inhaled
corticosteroid (ICS) treatment. Our findings suggest that basophils may be
particularly important in eosinophilic asthma and that sputum basophil assessment
could be a useful additional indicator of "TH2-high" asthma.
PMID- 28426172
TI - Distinct Roles of Th17 and Th1 Cells in Inflammatory Responses Associated with
the Presentation of Paucibacillary Leprosy and Leprosy Reactions.
AB - It is well established that helper T cell responses influence resistance or
susceptibility to Mycobacterium leprae infection, but the role of more recently
described helper T cell subsets in determining severity is less clear. To
investigate the involvement of Th17 cells in the pathogenesis of leprosy, we
determined the immune profile with variant presentations of leprosy. Firstly, IL
17A, IFN-gamma and IL-10 were evaluated in conjunction with CD4+ T cell staining
by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous
leprosy (LL) patients. Secondly, inflammatory cytokines were measured by
multiplex assay of serum samples from Multibacillary (MB, n = 28) and
Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23).
Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n
= 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed
by flow cytometry used to determine the phenotype of cytokine-producing cells.
Lesions from TT patients were found to have more CD4+ IL-17A+ cells than those
from LL patients. Higher concentrations of IL-17A and IL-1beta were observed in
serum from PB than MB patients. The highest serum IFN-gamma concentrations were,
however, detected in sera from MB patients that developed leprosy reactions (MB
LR+ ). Together, these results indicate that Th1 cells were associated with both
the PB presentation and also with leprosy reactions. In contrast, Th17 cells were
associated with an effective inflammatory response that is present in the PB
forms but were not predictive of leprosy reactions in MB patients.
PMID- 28426173
TI - Spinal Arachnoid Diverticula: Outcome in 96 Medically or Surgically Treated Dogs.
AB - BACKGROUND: Little is reported about the role of medical management in the
treatment of spinal arachnoid diverticula (SAD) in dogs. OBJECTIVES: To describe
the outcome of 96 dogs treated medically or surgically for SAD. ANIMALS: Ninety
six dogs with SAD. METHODS: Retrospective case series. Medical records were
searched for spinal arachnoid diverticula and all dogs with information on
treatment were included. Outcome was assessed with a standardized questionnaire.
RESULTS: Fifty dogs were managed medically and 46 dogs were treated surgically.
Dogs that underwent surgery were significantly younger than dogs that received
medical management. No other variables, related to clinical presentation, were
significantly different between both groups of dogs. The median follow-up time
was 16 months (1-90 months) in the medically treated and 23 months (1-94 months)
in the surgically treated group. Of the 38 dogs treated surgically with available
long-term follow-up, 82% (n = 31) improved, 3% (n = 1) remained stable and 16% (n
= 6) deteriorated after surgery. Of the 37 dogs treated medically with available
long-term follow-up, 30% (n = 11) improved, 30% (n = 11) remained stable, and 40%
(n = 15) deteriorated. Surgical treatment was more often associated with clinical
improvement compared to medical management (P = .0002). CONCLUSIONS AND CLINICAL
IMPORTANCE: The results of this study suggest that surgical treatment might be
superior to medical treatment in the management of SAD in dogs. Further studies
with standardized patient care are warranted.
PMID- 28426174
TI - Solid-Phase Synthesis of a Seventh-Generation Inverse Poly(amidoamine) Dendrimer:
Importance of the Loading Ratio on the Resin.
AB - Here, this study overcomes the current barriers to efficient solid-phase
synthesis of high-generation dendrimers by decreasing the loading ratio on the
resin. G7 inverse poly(amidoamine) dendrimer is now prepared, for the first time,
through a solid-phase synthesis using only 50% of the available reactive sites
and by choosing a large resin. This preparation takes only 15 d to afford highly
pure product in 80% yield with precipitation being the only purification
procedure used. The results clearly show the amount of the initial monomer loaded
on the resin to be a vital factor for the ability to use solid-phase synthesis to
produce large dendrimers. This finding also sets stage for the applications of
solid-phase synthesis for the preparation of other macromolecules.
PMID- 28426175
TI - Differences in xylem and leaf hydraulic traits explain differences in drought
tolerance among mature Amazon rainforest trees.
AB - Considerable uncertainty surrounds the impacts of anthropogenic climate change on
the composition and structure of Amazon forests. Building upon results from two
large-scale ecosystem drought experiments in the eastern Brazilian Amazon that
observed increases in mortality rates among some tree species but not others, in
this study we investigate the physiological traits underpinning these
differential demographic responses. Xylem pressure at 50% conductivity (xylem-P50
), leaf turgor loss point (TLP), cellular osmotic potential (pio ), and cellular
bulk modulus of elasticity (epsilon), all traits mechanistically linked to
drought tolerance, were measured on upper canopy branches and leaves of mature
trees from selected species growing at the two drought experiment sites. Each
species was placed a priori into one of four plant functional type (PFT)
categories: drought-tolerant versus drought-intolerant based on observed
mortality rates, and subdivided into early- versus late-successional based on
wood density. We tested the hypotheses that the measured traits would be
significantly different between the four PFTs and that they would be spatially
conserved across the two experimental sites. Xylem-P50 , TLP, and pio , but not
epsilon, occurred at significantly higher water potentials for the drought
intolerant PFT compared to the drought-tolerant PFT; however, there were no
significant differences between the early- and late-successional PFTs. These
results suggest that these three traits are important for determining drought
tolerance, and are largely independent of wood density-a trait commonly
associated with successional status. Differences in these physiological traits
that occurred between the drought-tolerant and drought-intolerant PFTs were
conserved between the two research sites, even though they had different soil
types and dry-season lengths. This more detailed understanding of how xylem and
leaf hydraulic traits vary between co-occuring drought-tolerant and drought
intolerant tropical tree species promises to facilitate a much-needed improvement
in the representation of plant hydraulics within terrestrial ecosystem and
biosphere models, which will enhance our ability to make robust predictions of
how future changes in climate will affect tropical forests.
PMID- 28426176
TI - UHPLC-MS/MS method for the simultaneous quantitation of five anthraquinones and
gallic acid in rat plasma after oral administration of prepared rhubarb decoction
and its application to a pharmacokinetic study in normal and acute blood stasis
rats.
AB - Prepared rhubarb, as one of the main processed products of rhubarb, has a good
effect on promoting blood circulation. In this paper we describe a rapid,
sensitive, and selective ultra-fast liquid chromatography with tandem mass
spectrometry method for simultaneous quantification of five anthraquinones
(rhein, aloe-emodin, chrysophanol, emodin, and physcion) and gallic acid in
plasma. Chromatographic separation was performed on an Extend C18 column at the
temperature of 30 degrees C using a mobile phase that consisted of 0.1% aqueous
formic acid and acetonitrile. Satisfactory linearity, precision, accuracy,
extraction recovery, and matrix effect have been achieved. Then, the validated
method was successfully applied to a comparative pharmacokinetic study. The
results might be helpful for guiding clinical application of prepared rhubarb in
the future.
PMID- 28426177
TI - An efficient cleanup method coupled with gas chromatography and mass spectrometry
for multi-pesticides residue analysis in complex plant matrices.
AB - We aimed to develop an efficient cleanup method for multi-pesticides residue
analysis in complex plant matrices, shallot, ginger, garlic, onion, leek, and
celery. Column chromatography was used as the cleanup method and fabricated with
florisil and graphitized carbon black as the adsorbents. The amount of the
graphitized carbon black adsorbent and the choice of the elution solvent were
systematically investigated for exploring the best combination. The target
pesticides covered organochlorine, pyrethroid, and organophosphorus pesticides,
and were 38 in total. The method validation and comparison were performed to
verify its feasibility and advantages in operation convenience and purification
efficiency. The method limit of quantitation varied from 0.01 to 0.03 mg/kg,
which depends on the pesticides and the sample matrices. The recoveries of the
pesticides ranged from 60.5 to 128% (RSD <= 19.0%) at the spiked concentration
level of 0.01 (or 0.03) mg/kg and 62.9 to 130% (RSD <= 13.0%) at 0.1 mg/kg.
Compared with the commercial cleanup solid-phase extraction cartridges, the
present adsorbent combination displayed better purification effect and shorter
sample pretreatment time, demonstrating potential application prospect in the
complex matrix sample analysis.
PMID- 28426178
TI - Multiplexing N-glycan analysis by DNA analyzer.
AB - Analysis of N-glycan structures has been gaining attentions over the years due to
their critical importance to biopharma-based applications and growing roles in
biological research. Glycan profiling is also critical to the development of
biosimilar drugs. The detailed characterization of N-glycosylation is mandatory
because it is a nontemplate driven process and that significantly influences
critical properties such as bio-safety and bio-activity. The ability to
comprehensively characterize highly complex mixtures of N-glycans has been
analytically challenging and stimulating because of the difficulties in both the
structure complexity and time-consuming sample pretreatment procedures. CE-LIF is
one of the typical techniques for N-glycan analysis due to its high separation
efficiency. In this paper, a 16-capillary DNA analyzer was coupled with a
magnetic bead glycan purification method to accelerate the sample preparation
procedure and therefore increase N-glycan assay throughput. Routinely, the
labeling dye used for CE-LIF is 8-aminopyrene-1,3,6-trisulfonic acid, while the
typical identification method involves matching migration times with database
entries. Two new fluorescent dyes were used to either cross-validate and increase
the glycan identification precision or simplify sample preparation steps.
Exoglycosidase studies were carried out using neuramididase, galactosidase, and
fucosidase to confirm the results of three dye cross-validation. The optimized
method combines the parallel separation capacity of multiple-capillary separation
with three labeling dyes, magnetic bead assisted preparation, and exoglycosidase
treatment to allow rapid and accurate analysis of N-glycans. These new methods
provided enough useful structural information to permit N-glycan structure
elucidation with only one sample injection.
PMID- 28426179
TI - Novel, Selective, and Developable Dopamine D3 Antagonists with a Modified "Amino"
Region.
AB - This Minireview describes a presentation made at the XXIV National Meeting in
Medicinal Chemistry (NMMC) held in Perugia (Italy), September 11-14, 2016. It
relates to the discovery of novel templates of the so-called "amino" region of
dopamine D3 receptor antagonists. Moving from the early scaffolds, which were
modified in the amine portion, this review discusses the variations that led to
the discovery of new systems published in 2016, which allowed the identification
of compounds endowed with great selectivity over the dopamine D2 receptor and the
human ether-a-go-go-related gene (hERG) ion channel. The main efforts in
characterizing these compounds were devoted not only to determining their potency
and selectivity relative to closely associated targets (e.g., the dopamine D2
receptor), but to ensure a large therapeutic window versus liability points such
as hERG. In particular, we present examples of derivatives with selectivities
greater than 2000-fold. Furthermore, much focus is devoted to the overall
developability of the scaffolds, ensuring that appropriate physicochemical and
pharmacokinetic parameters are present in all compounds progressing through the
screening cascade.
PMID- 28426180
TI - Secondary Sensitivity Control of Silver-Nanowire-Based Resistive-Type Strain
Sensors by Geometric Modulation of the Elastomer Substrate.
AB - A secondary method for modulation of the sensitivity in silver nanowire (AgNW)
resistive-type strain sensors without the need to change the material or coating
process in the sensory layer is demonstrated. Instead of using a planar elastomer
(polydimethylsiloxane is used in this study) substrate, diverse relief structures
are introduced to induce nonuniform and complex strain within the elastic
substrate and thereby different distributions of the crack density of the AgNWs
upon stretching, which plays an important role in the modulation of the gauge
factor (GF). Analysis of the sensory layer and mechanical studies reveal that a
lower height ratio and greater number of trenches enhance the sensor sensitivity,
for example, reaching a GF of 926 at 9.6% in this study. The demonstration of
wrist-motion sensors using the technology illustrates the feasibility of using
relief structures for various types of sensors and sensitivity ranges using an
identical sensor layer.
PMID- 28426181
TI - Prognostic significance of cachexia score assessed by CT in male patients with
small cell lung cancer.
AB - To determine the prognostic significance of CT-determined cachexia scores (CSs)
in 127 consecutive male small cell lung cancer (SCLC) patients, cross-sectional
areas of muscle and fat tissues at the third lumbar vertebra (L3) were
retrospectively measured on baseline CT images. CSs were determined based on the
presence of sarcopenia and/or adipopenia. According to the presence of sarcopenia
(L3 muscle index <55 cm2 /m2 , 86.8%) and adipopenia (L3 fat index <22 cm2 /m2 ,
11.8%), CSs were defined as follows: CS2 (sarcopenia and adipopenia, 11.8%), CS1
(sarcopenia only, 74.8%) and CS0 (13.4%). CS2 was significantly related to lower
body mass index (p < .001) and poor performance status (p = .002), and patients
with CS2 had shorter OS than patients with CS1 or CS0 (median OS, 5.0 months vs.
8.9 months vs. 18.3 months; p = .007). Multivariable analysis revealed that CS
was an independent prognostic factor of poor survival (HR, 1.99 for CS1 and 2.59
for CS2, p = .036 and .023, CS0 as a reference), along with extensive stage (p <
.001), supportive care only (p < .001) and an elevated lactate dehydrogenase (p =
.005). CT-determined CSs, based on the presence of sarcopenia and/or adipopenia,
could be used to predict prognosis in male SCLC.
PMID- 28426182
TI - Usefulness and accuracy of MALDI-TOF mass spectrometry as a supplementary tool to
identify mosquito vector species and to invest in development of international
database.
AB - Arthropod-borne diseases are important causes of morbidity and mortality. The
identification of vector species relies mainly on morphological features and/or
molecular biology tools. The first method requires specific technical skills and
may result in misidentifications, and the second method is time-consuming and
expensive. The aim of the present study is to assess the usefulness and accuracy
of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
(MALDI-TOF MS) as a supplementary tool with which to identify mosquito vector
species and to invest in the creation of an international database. A total of 89
specimens belonging to 10 mosquito species were selected for the extraction of
proteins from legs and for the establishment of a reference database. A blind
test with 123 mosquitoes was performed to validate the MS method. Results showed
that: (a) the spectra obtained in the study with a given species differed from
the spectra of the same species collected in another country, which highlights
the need for an international database; (b) MALDI-TOF MS is an accurate method
for the rapid identification of mosquito species that are referenced in a
database; (c) MALDI-TOF MS allows the separation of groups or complex species,
and (d) laboratory specimens undergo a loss of proteins compared with those
isolated in the field. In conclusion, MALDI-TOF MS is a useful supplementary tool
for mosquito identification and can help inform vector control.
PMID- 28426183
TI - Mass Production of Cell-Laden Calcium Alginate Particles with Centrifugal Force.
AB - This paper describes a centrifuge-based device for oil-free and mass production
of calcium-alginate (Ca-alginate) particles. The device is composed of four
components: a tank with a glass capillary for forming sodium alginate droplets, a
collecting bath with calcium chloride (CaCl2 ) solution, a waste liquid box, and
a bypass channel bridged between the collecting bath and the waste liquid box.
When the device is centrifuged, extra CaCl2 solution in the collecting bath is
delivered to the waste liquid box to maintain the appropriate liquid level of
CaCl2 solution for the production of monodisperse Ca-alginate particles. The
proposed device enables oil-free production of over 45 000 uniformly sized Ca
alginate particles in a single 240 s process, whereas using the conventional
method with only a glass capillary, ~1000 particles are formed within the same
processing time. Because of the high biocompatibility of the oil-free process,
the device is applicable to cell encapsulation in Ca-alginate particles with high
cell viability, as well as the formation of a macroscopic 3D cellular structure
using Ca-alginate particles covered with cells as assembly modules. These results
suggest that the device can be a useful tool for preparing experimental platforms
in biomedical and tissue engineering fields.
PMID- 28426184
TI - Alterations in mandibular morphology associated with glypican 1 and glypican 3
gene mutations.
AB - OBJECTIVES: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that
act downstream in many of the signalling pathways associated with
craniosynostosis. Morphometric data from GPC-knockout mice were analysed to
determine whether elimination of GPC1 and GPC3 genes would alter mandibular
morphology. SETTING AND SAMPLE POPULATION: The murine model included five male
and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild
type (control) groups. Female GPC3-knockout mice had a very high rate of
perinatal lethality, and therefore, only five males were included in this group.
METHODS: The mandibular morphology of GPC1-knockout (n=10), GPC3-knockout (n=5),
GPC1/GPC3-knockout (n=10) and wild-type (n=10) mice was compared by analysing
five landmark-based linear dimensions: anterior and posterior lengths, as well as
ascending, descending and posterior heights. Measurements were recorded on three
dimensional micro-CT reconstructions. RESULTS: GPC3-knockout mandibles were
larger than wild-type mandibles for all dimensions (P<.05). Mandibular heights
were more affected than lengths. A decreasing trend of mandibular dimensions
across the mouse groups (GPC3-knockout>GPC1/GPC3-knockout>GPC1-knockout=wild
type) (P<.05) indicated that an increase in mandibular size was associated with
increased GPC3 expression, but not GPC1. CONCLUSIONS: Alterations in GPC3
expression are likely to mediate changes to mandibular size in craniosynostosis.
These findings have potential future applications in the prevention and treatment
of craniosynostosis and associated craniofacial dysmorphology.
PMID- 28426186
TI - Issue at the Heart of Advancing the De-Adoption of Low-Value Care. Proceedings
from an expert roundtable.
AB - Identifying and paying for value has become a recurrent theme of health care
reforms. Its corollary, reducing the prevalence of, and resources directed to,
ineffective or marginally effective care, has received far less attention. In
July 2016, the University of Pennsylvania's Leonard Davis Institute of Health
Economics (LDI) convened a diverse set of national leaders and stakeholders
representing industry, think-tanks, provider and patient groups, and academic
experts to tackle how health systems, payers, and providers can spur the 'de
adoption' of medical practices and technologies no longer considered
valuable.While the roundtable of experts unanimously supports the need for de
adoption and current efforts to curb the use of low-value practices or
technologies, they identified four specific polarities at the heart of the debate
about how best to build the momentum around deadoption, and move it forward. They
are: 1) value (targeting ineffective, even harmful, care or expanding efforts to
address care of limited value); 2) resource allocation (spending less or
redirecting spending); 3) quality improvement (a subset of QI or a distinct
process); 4) level of intervention (policy, payment, provider, or organization).
In addition to these polarities, several key questions emerged that form
practical next steps for advancing de-adoption activities. With an eye toward
advancing de-adoption, this brief summarizes the polarities and questions that
suggest priorities for a future research agenda and policy-relevant action steps.
PMID- 28426185
TI - Integrated HIV care and service engagement among people living with HIV who use
drugs in a setting with a community-wide treatment as prevention initiative: a
qualitative study in Vancouver, Canada.
AB - INTRODUCTION: Social-structural inequities impede access to, and retention in,
HIV care among structurally vulnerable people living with HIV (PLHIV) who use
drugs. The resulting disparities in HIV-related outcomes among PLHIV who use
drugs pose barriers to the optimization of HIV treatment as prevention (TasP)
initiatives. We undertook this study to examine engagement with, and impacts of,
an integrated HIV care services model tailored to the needs of PLHIV who use
drugs in Vancouver, Canada - a setting with a community-wide TasP initiative.
METHODS: We conducted qualitative interviews with 30 PLHIV who use drugs
recruited from the Dr. Peter Centre, an HIV care facility operating under an
integrated services model and harm reduction approach. We employed novel
analytical techniques to analyse participants' service trajectories within this
facility to understand how this HIV service environment influences access to, and
retention in, HIV care among structurally vulnerable PLHIV who use drugs.
RESULTS: Our findings demonstrate that participants' structural vulnerability
shaped their engagement with the HIV care facility that provided access to
resources that facilitated retention in HIV care and antiretroviral treatment
adherence. Additionally, the integrated service environment helped reduce burdens
associated with living in extreme poverty by meeting participants' subsistence
(e.g. food, shelter) needs. Moreover, access to multiple supports created a
structured environment in which participants could develop routine service use
patterns and have prolonged engagement with supportive care services. Our
findings demonstrate that low-barrier service models can mitigate social and
structural barriers to HIV care and complement TasP initiatives for PLHIV who use
drugs. CONCLUSION: These findings highlight the critical role of integrated
service models in promoting access to health and support services for
structurally vulnerable PLHIV. Complementing structural interventions with
integrated service models that are tailored to the needs of structurally
vulnerable PLHIV who use drugs will be pursuant to the goals of TasP.
PMID- 28426189
TI - Issues Confronting Rural Pharmacies after a Decade of Medicare Part D.
AB - Purpose. The RUPRI Center for Rural Health Policy Analysis has been monitoring
the status of rural independent pharmacies since the implementation of Medicare
Part D in 2005. After a decade of Part D, we reassess in this brief the issues
that concern rural pharmacies and may ultimately challenge their provision of
services. This reassessment is based on survey responses from rural pharmacists.
Key Findings: (1) Rural pharmacists indicated that two challenges--direct and
indirect remuneration (DIR) fees, and delayed maximum allowable cost (MAC)
adjustment--ranked highest on scales of both magnitude and immediacy. Nearly
eighty (79.8) percent of respondents reported DIR fees as a very large magnitude
challenge, with 83.3 percent reporting this as a very immediate challenge.
Seventy-eight percent of respondents reported MACs not being updated quickly
enough to reflect changes in wholesale drug costs as a very large magnitude
challenge, with 79.7 percent indicating it as a very immediate challenge. (2)
Medicare Part D continues to be a concern for rural pharmacies--58.8 percent of
pharmacists said being an out-of-network pharmacy for Part D plans was a very
large magnitude challenge (an additional 29.0 percent said large magnitude) and
60.5 percent said it was a very immediate challenge (an additional 28.1 percent
said moderately immediate). (3) Pharmacy staffing, competition from pharmacy
chains, and contracts for services for Medicaid patients were less likely to be
reported as significant or immediate challenges.
PMID- 28426190
TI - Robust Polymer Electrolyte Membranes with High Ambient-Temperature Lithium-Ion
Conductivity via Polymerization-Induced Microphase Separation.
AB - Mechanically robust polymer electrolyte membranes (PEMs) exhibiting high ionic
conductivity at ambient temperature are a prerequisite for next-generation
electrochemical devices. We utilized a polymerization-induced microphase
separation (PIMS) strategy to prepare nanostructured materials comprising
continuous conducting nanochannels intertwined with a mechanically and thermally
robust cross-linked polymeric framework. Addition of succinonitrile (SN) rendered
the poly(ethylene oxide)/lithium (Li) salt conducting domains completely
amorphous, resulting in outstanding conductivities (~0.35 mS/cm) at 30 degrees
C. Concurrently, a densely cross-linked polystyrene framework provided mechanical
robustness (modulus E' ~ 0.3 GPa at 30 degrees C) to the hybrid material. This
work highlights a facile, single-pot strategy involving a homogeneous liquid
reaction precursor that yields a high-performance ion-conducting membrane
attractive for lithium-battery applications.
PMID- 28426191
TI - Genome-Wide Abolishment of Mobile Genetic Elements Using Genome Shuffling and
CRISPR/Cas-Assisted MAGE Allows the Efficient Stabilization of a Bacterial
Chassis.
AB - The ideal bacterial chassis provides a simplified, stable and predictable host
environment for synthetic biological circuits. Mutability and evolution can,
however, compromise stability, leading to deterioration of artificial genetic
constructs. By eliminating certain sources of instability, these undesired
genetic changes can be mitigated. Specifically, deletion of prophages and
insertion sequences, nonessential constituents of bacterial genomes, has been
shown to be beneficial in cellular and genetic stabilization. Here, we sought to
establish a rapid methodology to improve the stability of microbial hosts. The
novel workflow involves genome shuffling between a mobile genetic element-free
strain and the target cell, and subsequent rounds of CRISPR/Cas-assisted MAGE on
multiplex targets. The power and speed of the procedure was demonstrated on E.
coli BL21(DE3), a host routinely used for plasmid-based heterologous protein
expression. All 9 prophages and 50 insertion elements were efficiently deleted or
inactivated. Together with additional targeted manipulations (e.g., inactivation
of error-prone DNA-polymerases), the changes resulted in an improved bacterial
host with a hybrid (harboring segments of K-12 DNA), 9%-downsized and clean
genome. The combined capacity of phage-mediated generalized transduction and
CRISPR/Cas-selected MAGE offers a way for rapid, large scale editing of bacterial
genomes.
PMID- 28426192
TI - Profiling Cellular Substrates of Lysine Acetyltransferases GCN5 and p300 with
Orthogonal Labeling and Click Chemistry.
AB - p300 and GCN5 are two representative lysine acetyltransferases (KATs) in
mammalian cells. It was recently reported that they possess multiple
acyltransferase activities including acetylation, propionylation, and
butyrylation of the epsilon-amino group of lysine residues of histones and non
histone protein substrates. Although thousands of acetylated substrates and
acetylation sites have been identified by mass spectrometry-based proteomic
screening, our knowledge about the causative connections between individual KAT
members and their corresponding sub-acylomes remain very limited. Herein, we
applied 3-azidopropionyl CoA (3AZ-CoA) as a bioorthogonal surrogate of acetyl-,
propionyl- and butyryl-CoA for KAT substrate identification. We successfully
attached the azide as a chemical warhead to cellular substrates of wild-type p300
and engineered GCN5. The substrates were subsequently labeled with biotin tag
through the copper-catalyzed azide-alkyne cycloaddition (CuAAC). Following
protein enrichment on streptavidin-coated resin, we conducted LC-MS/MS studies
from which more than four hundred proteins were identified as GCN5 or p300
substrate candidates. These proteins are either p300- or GCN5-unique or shared by
the two KATs and are extensively involved in various biological events including
gene expression, cell cycle, and cellular metabolism. We also experimentally
validated two novel substrates of GCN5, that is, IQGAP1 and SMC1. These results
demonstrate extensive engagement of GCN5 and p300 in cellular pathways and
provide new insights into understanding their functions in specific biological
processes.
PMID- 28426193
TI - The Glutathione Conundrum: Stoichiometric Disconnect between Its Formation and
Oxidative Stress.
AB - Glutathione (GSH) is the most abundant antioxidant and is believed to maintain
redox potential in tissues, cells, and individual compartments. However, GSH
concentrations in some tumor cells and tissues have been reported to be as high
as 1-10 mM, a concentration that is up to 10,000-fold higher than that of
reactive oxygen species. Critical quantitative evaluation of glutathione's
proposed functions suggests that glutathione is an amino acid checkpoint. In this
role, glutathione contributes to regulating cell proliferation and apoptosis,
pending amino acid availability.
PMID- 28426194
TI - Development of a Porous Coordination Polymer with a High Gas Capacity Using a
Thiophene-Based Bent Tetracarboxylate Ligand.
AB - A new porous coordination polymer (PCP) based on a ligand with a unique bent
angle bearing a thiophene-bridged bent carboxylate ligand and the Cu2+ ion was
synthesized and structurally characterized. The structure has a pillared-layer
framework based on a kagome-like layer with aromatic partition groups. It
exhibits a high CO2 uptake of 180 mL(STP)/g at 1 bar, and 400 mL(STP)/g at 30 bar
at 273 K. The uptakes of C2H2 and C2H4 reach 164 and 160 mL(STP)/g at 298 K and 1
bar, with good selectivity of C2H2 and C2H4 over CH4, both of which are among the
highest levels of reported PCPs.
PMID- 28426195
TI - One-Step Fabrication of Non-Fluorinated Transparent Super-Repellent Surfaces with
Tunable Wettability Functioning in Both Air and Oil.
AB - In this paper, we have developed a one-step thermal treatment of
polydimethylsiloxane (PDMS) liquid to create transparent super-repellent surface
(TSS) and super-repellent powder. They are super-repellent toward water and
ethylene glycol. During the one-step thermal treatment, PDMS soot is generated
and deposited onto a glass slide (GS) surface to fabricate the TSS without
fluorosilane modification. The facilely obtained TSS presented
superhydrophobicity and self-cleaning property when immersed into very low
surface tension oils such as petroleum ether, hexadecane, peanut oil, and
dodecane. Interestingly, by controlling heating time and temperature, wettability
of the treated GS surface and the remained white powder can be regulated. The
mechanism of tunable wettability was revealed and analyzed by investigating the
variations of surface morphology and chemical composition. More importantly, TSS
was able to repel highly corrosive aqua regia and saturated NaOH solutions. TSS
maintained excellent superhydrophobicity even after chemical and mechanical
damages. This simple thermal deposition method was also applicable for other
thermally stable substrates to achieve super-repellency, which are believed to
find very promising applications.
PMID- 28426196
TI - Chiral Inorganic Nanostructures.
AB - The field of chiral inorganic nanostructures is rapidly expanding. It started
from the observation of strong circular dichroism during the synthesis of
individual nanoparticles (NPs) and their assemblies and expanded to sophisticated
synthetic protocols involving nanostructures from metals, semiconductors,
ceramics, and nanocarbons. Besides the well-established chirality transfer from
bioorganic molecules, other methods to impart handedness to nanoscale matter
specific to inorganic materials were discovered, including three-dimentional
lithography, multiphoton chirality transfer, polarization effects in nanoscale
assemblies, and others. Multiple chiral geometries were observed with
characteristic scales from angstroms to microns. Uniquely high values of chiral
anisotropy factors that spurred the development of the field and differentiate it
from chiral structures studied before, are now well understood; they originate
from strong resonances of incident electromagnetic waves with plasmonic and
excitonic states typical for metals and semiconductors. At the same time,
distinct similarities with chiral supramolecular and biological systems also
emerged. They can be seen in the synthesis and separation methods, chemical
properties of individual NPs, geometries of the nanoparticle assemblies, and
interactions with biological membranes. Their analysis can help us understand in
greater depth the role of chiral asymmetry in nature inclusive of both earth and
space. Consideration of both differences and similarities between chiral
inorganic, organic, and biological nanostructures will also accelerate the
development of technologies based on chiroplasmonic and chiroexcitonic effects.
This review will cover both experiment and theory of chiral nanostructures
starting with the origin and multiple components of mirror asymmetry of
individual NPs and their assemblies. We shall consider four different types of
chirality in nanostructures and related physical, chemical, and biological
effects. Synthetic methods for chiral inorganic nanostructures are systematized
according to chirality types, materials, and scales. We also assess technological
prospects of chiral inorganic materials with current front runners being
biosensing, chiral catalysis, and chiral photonics. Prospective venues for future
fundamental research are discussed in the conclusion of this review.
PMID- 28426197
TI - Photoluminescence Segmentation within Individual Hexagonal Monolayer Tungsten
Disulfide Domains Grown by Chemical Vapor Deposition.
AB - We show that hexagonal domains of monolayer tungsten disulfide (WS2) grown by
chemical vapor deposition (CVD) with powder precursors can have discrete
segmentation in their photoluminescence (PL) emission intensity, forming
symmetric patterns with alternating bright and dark regions. Two-dimensional maps
of the PL reveal significant reduction within the segments associated with the
longest sides of the hexagonal domains. Analysis of the PL spectra shows
differences in the exciton to trion ratio, indicating variations in the exciton
recombination dynamics. Monolayers of WS2 hexagonal islands transferred to new
substrates still exhibit this PL segmentation, ruling out local strain in the
regions as the dominant cause. High-power laser irradiation causes preferential
degradation of the bright segments by sulfur removal, indicating the presence of
a more defective region that is higher in oxidative reactivity. Atomic force
microscopy (AFM) images of topography and amplitude modes show uniform thickness
of the WS2 domains and no signs of segmentation. However, AFM phase maps do show
the same segmentation of the domain as the PL maps and indicate that it is caused
by some kind of structural difference that we could not clearly identify. These
results provide important insights into the spatially varying properties of these
CVD-grown transition metal dichalcogenide materials, which may be important for
their effective implementation in fast photo sensors and optical switches.
PMID- 28426198
TI - Unified Biosynthetic Origin of the Benzodipyrrole Subunits in CC-1065.
AB - CC-1065 is the first characterized member of a family of naturally occurring
antibiotics including yatakemycin and duocarmycins with exceptionally potent
antitumor activity. CC-1065 contains three benzodipyrroles (1a-, 1b-, and 1c-) of
which the 1a-subunit is remarkable by being composed of a cyclopropane ring, and
the mechanism for the biological formation of benzodipyrrole rings remains
elusive. Previously, biosynthetic studies of CC-1065 were limited to
radioactively labeled precursor feeding experiments, which showed that tyrosine
(Tyr) and serine (Ser) were incorporated into the two benzodipyrrole (1b- and 1c
) subunits via the same mode but that this was different from the key
cyclopropabenzodipyrrole (1a-) subunit with N1-C2-C3 derived from Ser. Herein,
the biosynthetic gene cluster of CC-1065 has been cloned, analyzed, and
characterized by a series of gene inactivations. Significantly, a key
intermediate bearing a C7-OH group derived from a Deltac10C mutant exhibited
improved cytotoxicity. Moreover, this data inspired us to suspect that the 1a
subunit might employ the same precursor incorporation mode as the 1b- and 1c
subunits. Subsequently, 13C-labeled Tyr feeding experiments confirmed that the N1
C2-C3 is originated from Tyr via DOPA as an intermediate. Collectively, a
biosynthetic pathway of benzodipyrrole is proposed featuring a revised and
unified precursor incorporation mode, which implicates an oxidative cyclization
strategy for the assembly of benzodipyrrole. This work sets the stage for further
study of enzymatic mechanisms and combinatorial biosynthesis for new DNA
alkylating analogues.
PMID- 28426199
TI - Sequestering Soil Organic Carbon: A Nitrogen Dilemma.
PMID- 28426200
TI - Facile Design and Fabrication of Superwetting Surfaces with Excellent Wear
Resistance.
AB - Preparation of mechanically durable superwetting surfaces is imperative, yet
challenging for the wide range of real applications where high durability is
required. Mechanical wear on superwetting surfaces usually degrades weak
roughness, leading to loss of functions. In this study, wear-resistant
superhydrophilic/underwater superoleophobic and superhydrophobic surfaces are
prepared by anchoring reinforced coatings via adhesive-swelling and adhesive
bonding processes, respectively. The results of the sandpaper abrasion (grit no.
600, 24 kPa) show that superhydrophilic nylon/SiO2 coatings and superhydrophobic
polyurethane/TiO2 coatings retain their functions after suffering the abrasion
distances of 70 cm and more than 1000 cm, respectively. Reinforced coatings
formed by consecutive roughness and improved adhesion between coatings and
substrates are responsible for repeatedly generated superwettability after
exposure to mechanical stresses and demonstrated to be feasible for designing
wear-resistant superwetting surfaces. Furthermore, this novel architecture of
"reinforced coating with consecutive roughness + high adhesion" may demand
desired coating materials and reliable coating-fixing techniques for sustaining
sufficient roughness and is superior to currently existing technologies in
advancing wear-resistance of superwetting surfaces.
PMID- 28426201
TI - Exploiting Solvate Ionic Liquids for Amine Gas Analysis on a Quartz Crystal
Microbalance.
AB - We demonstrated in this work the usefulness of solvate ionic liquids SIL 3 and
SIL 4 for chemoselective detection of amine gases on a quartz crystal
microbalance. This detection of gaseous amines was achieved by nucleophilic
aromatic addition reactions with super electrophilic SIL 3 or SIL 4 thin-coated
on quartz chips. Starting with inexpensive reagents, functional SIL 3 and SIL 4
could be readily synthesized in two short steps with high isolated yield (81 and
77%, respectively). The QCM platform developed in this work is readily applicable
and highly sensitive to low molecular weight amine gases: for propylamine gas at
10 Hz decrease in resonance frequency, the sensitivity of detection using SIL 4
was 5.4 ppb. This simple and convenient assembly of neutral ligands (e.g., 1a and
1b) with Li+ ion to afford room temperature ionic liquids should be of great
importance for a myriad of applications. To the best of our knowledge, no example
to date of reports based on nucleophilic aromatic addition reactions
demonstrating sensitive amine gas detection in solvate ionic liquids on a QCM has
been reported. Furthermore, because of the high color intensity of the
Meisenheimer complexes formed, our preliminary result showed that SIL 4 loaded on
copier paper can be used not only as a portable amine gas sensor but also as a
potential invisible ink that is only revealed by amine vapor.
PMID- 28426202
TI - Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating
Tumor Hypoxia.
AB - Hypoxia development in tumor is closely associated with its increased
aggressiveness and strong resistance to therapy, leading to the poor prognosis in
several cancer types. Clinically, invasive oxygen microelectrode and high dosage
radiotherapy are often utilized to accurately detect and effectively fight
hypoxia. Recently, however, there has been a surge of interdisciplinary research
aiming at developing functional molecules and nanomaterials that can be used to
noninvasively image and efficiently treat hypoxic tumors. In this review, we will
provide an overview of the reports published to date on the imaging and therapy
of hypoxic tumors. First, we will present the design concepts and engineering of
various hypoxia-responsive probes that can be applied to image hypoxia
noninvasively, in an order of fluorescent imaging, positron emission tomography,
magnetic resonance imaging, and photoacoustic imaging. Then, we will summarize
the up-to-date functional nanomaterials which can be used for the effective
treatments of tumor hypoxia. The well-established chemical functions of these
elaborately designed nanostructures will enable clinicians to adopt specific
treatment concepts by overcoming or even utilizing hypoxia. Finally, challenges
and future perspectives facing the researchers in the field will be discussed.
PMID- 28426203
TI - Tyrosine Kinase Activation and Conformational Flexibility: Lessons from Src
Family Tyrosine Kinases.
AB - Protein kinases are enzymes that catalyze the covalent transfer of the gamma
phosphate of an adenosine triphosphate (ATP) molecule onto a tyrosine, serine,
threonine, or histidine residue in the substrate and thus send a chemical signal
to networks of downstream proteins. They are important cellular signaling enzymes
that regulate cell growth, proliferation, metabolism, differentiation, and
migration. Unregulated protein kinase activity is often associated with a wide
range of diseases, therefore making protein kinases major therapeutic targets. A
prototypical system of central interest to understand the regulation of kinase
activity is provided by tyrosine kinase c-Src, which belongs to the family of Src
related non-receptor tyrosine kinases (SFKs). Although the broad picture of
autoinhibition via the regulatory domains and via the phosphorylation of the C
terminal tail is well characterized from a structural point of view, a detailed
mechanistic understanding at the atomic-level is lacking. Advanced computational
methods based on all-atom molecular dynamics (MD) simulations are employed to
advance our understanding of tyrosine kinase activation. The computational
studies suggest that the isolated kinase domain (KD) is energetically most
favorable in the inactive conformation when the activation loop (A-loop) of the
KD is not phosphorylated. The KD makes transient visits to a catalytically
competent active-like conformation. The process of bimolecular trans
autophosphorylation of the A-loop eventually locks the KD in the active state.
Activating point mutations may act by slightly increasing the population of the
active-like conformation, enhancing the availability of the A-loop to be
phosphorylated. The Src-homology 2 (SH2) and Src-homology 3 (SH3) regulatory
domains, depending upon their configuration, either promote the inactive or the
active state of the kinase domain. In addition to the roles played by the SH3,
SH2, and KD, the Src-homology 4-Unique domain (SH4-U) region also serves as a key
moderator of substrate specificity and kinase function. Thus, a fundamental
understanding of the conformational propensity of the SH4-U region and how this
affects the association to the membrane surface are likely to lead to the
discovery of new intermediate states and alternate strategies for inhibition of
kinase activity for drug discovery. The existence of a multitude of KD
conformations poses a great challenge aimed at the design of specific inhibitors.
One promising computational strategy to explore the conformational flexibility of
the KD is to construct Markov state models from aggregated MD data.
PMID- 28426204
TI - Parameter Optimization for Interaction between C-Terminal Domains of HIV-1 Capsid
Protein.
AB - HIV-1 capsid proteins (CAs) assemble into a capsid that encloses the viral RNA.
The binding between a pair of C-terminal domains (CTDs) constitutes a major
interface in both the CA dimers and the large CA assemblies. Here, we attempt to
use a general residue-level coarse-grained model to describe the interaction
between two isolated CTDs in Monte Carlo simulations. With the standard
parameters that depend only on the residue types, the model predicts a much
weaker binding in comparison to the experiments. Detailed analysis reveals that
some Lennard-Jones parameters are not compatible with the experimental CTD dimer
structure, thus resulting in an unfavorable interaction energy. To improve the
model for the CTD binding, we introduce ad hoc modifications to a small number of
Lennard-Jones parameters for some specific pairs of residues at the binding
interface. Through a series of extensive Monte Carlo simulations, we identify the
optimal parameters for the CTD-CTD interactions. With the refined model
parameters, both the binding affinity (with a dissociation constant of 13 +/- 2
MUM) and the binding mode are in good agreement with the experimental data. This
study demonstrates that the general interaction model based on the Lennard-Jones
potential, with some modest adjustment of the parameters for key residues, could
correctly reproduce the reversible protein binding, thus potentially applicable
for simulating the thermodynamics of the CA assemblies.
PMID- 28426205
TI - Euro 6 Unregulated Pollutant Characterization and Statistical Analysis of After
Treatment Device and Driving-Condition Impact on Recent Passenger-Car Emissions.
AB - This study aims to measure and analyze unregulated compound emissions for two
Euro 6 diesel and gasoline vehicles. The vehicles were tested on a chassis
dynamometer under various driving cycles: Artemis driving cycles (urban, road,
and motorway), the New European Driving Cycle (NEDC) and the World Harmonized
Light-Duty Test Cycle (WLTC) for Europe, and world approval cycles. The emissions
of unregulated compounds (such as total particle number (PN) (over 5.6 nm); black
carbon (BC); NO2; benzene, toluene, ethylbenzene, and xylene (BTEX); carbonyl
compounds; and polycyclic aromatic hydrocarbons (PAHs)) were measured with
several online devices, and different samples were collected using cartridges and
quartz filters. Furthermore, a preliminary statistical analysis was performed on
eight Euro 4-6 diesel and gasoline vehicles to study the impacts of driving
conditions and after-treatment and engine technologies on emissions of regulated
and unregulated pollutants. The results indicate that urban conditions with cold
starts induce high emissions of BTEX and carbonyl compounds. Motorway conditions
are characterized by high emissions of particle numbers and CO, which mainly
induced by gasoline vehicles. Compared with gasoline vehicles, diesel vehicles
equipped with catalyzed or additive DPF emit fewer particles but more NOx and
carbonyl compounds.
PMID- 28426206
TI - Resonance Energies and Lifetimes from the Analytic Continuation of the Coupling
Constant Method: Robust Algorithms and a Critical Analysis.
AB - The energy of a metastable state can be computed by adding an artificial
stabilizing potential to the Hamiltonian, increasing the stabilization until the
metastable state is turned into a bound one, and then further increasing the
stabilization until enough bound-state data have been collected so that these can
be extrapolated back to vanishing stabilization. The lifetime of the metastable
state can be obtained from the same data, but only if the extrapolation is
performed by analytic continuation. This extrapolation method is called analytic
continuation of the coupling constant (ACCC). Here we introduce preconditioning
schemes for two of the three established extrapolation algorithms and critically
compare results from all three extrapolation schemes in a variety of situations:
As examples for resonance states serve the pi* temporary anions of ethylene and
formaldehyde as well as a model potential, which provides a case where input data
with full numeric precision are available. In the data collection step, three
different stabilizing potentials are employed, a Coulomb potential, a short-range
Coulomb potential, and a soft-box Voronoi potential. Effects of different orders
of the extrapolating Pade approximant are investigated, and last, the energy
range of input data for the extrapolation is studied. Moreover, all ACCC results
are compared to resonance parameters that have been independently obtained with
the same theoretical method, but with a different continuum approach-complex
scaling for the model and complex absorbing potentials for the temporary anions.
PMID- 28426207
TI - Fe3O4/FeNi Embedded Nanostructure and Its Kinetic Law for Selective Catalytic
Reduction of p-Nitrophenyl Compounds.
AB - To meet the requirement of high catalytic efficiency toward the reduction of p
nitrophenyl compounds, we designed a new one-dimensional Fe3O4/FeNi embedded
nanostructured catalyst synthesized by a one-pot controlling-growth-reduction
process in a solvothermal system, in which Fe3O4 phase was implanted in the base
of FeNi alloy. In the Fe3O4/FeNi catalyst system, the Fe3O4 embedded phase
attracts the nitro group of p-nitrophenyl compounds by its high-density
electrons, which can efficiently promote the activity of amorphous FeNi active
centers for selective catalysis toward the reduction of a range of p-nitrophenyl
compounds. Moreover, for the para-group in the nitrophenyl compounds, an
increasing electron-donating power contributes to a higher catalytic activity,
while electron-withdrawing power obtains the reverse case. Additionally, the
Fe3O4/FeNi composite nanocatalyst exhibited an outstanding cycling performance
over 20 times without obvious performance decay. This work opens an avenue to
design more powerful non-noble metal catalysts for green chemistry.
PMID- 28426208
TI - Global and Local Partitioning of the Charge Transferred in the Parr-Pearson
Model.
AB - Through a simple proposal, the charge transfer obtained from the cornerstone
theory of Parr and Pearson is partitioned, for each reactant, in two channels: an
electrophilic, through which the species accepts electrons, and the other, a
nucleophilic, where the species donates electrons. It is shown that this global
model allows us to determine unambiguously the charge-transfer mechanism
prevailing in a given reaction. The partitioning is extended to include local
effects through the Fukui functions of the reactants. This local model is applied
to several emblematic reactions in organic and inorganic chemistry, and we show
that besides improving the correlations obtained with the global model it
provides valuable information concerning the atoms in the reactants playing the
most important roles in the reaction and thus improving our understanding of the
reaction under study.
PMID- 28426209
TI - Channel-Assisted Proton Conduction Behavior in Hydroxyl-Rich Lanthanide-Based
Magnetic Metal-Organic Frameworks.
AB - Two new lanthanide-based 3D metal-organic frameworks (MOFs),
{[Ln(L)(Ox)(H2O)]n.xH2O} [Ln = Gd3+ and x = 3 (1) and Dy3+ and x = 1.5 (2); H2L =
mucic acid; OxH2 = oxalic acid] showing interesting magnetic properties and
channel-mediated proton conduction behavior, are presented here. Single-crystal X
ray structure analysis shows that, in complex 1, the overall structure originates
from the mucate-bridged gadolinium-based rectangular metallocycles. The packing
view reveals the presence the two types of hydrophilic 1D channels filled with
lattice water molecules, which are strongly hydrogen-bonded with coordinated
water along the a and b axes, whereas for complex 2, the 3D framework originates
from a carboxylate-bridged dysprosium-based criss-cross-type secondary building
block. Magnetic studies reveal that 1 exhibits a significant magnetic entropy
change (-DeltaSM) of 30.6 J kg-1 K-1 for DeltaH= 7 T at 3 K. Our electronic
structure calculations under the framework of density functional theory reveal
that exchange interactions between Gd3+ ions are weak and of the
antiferromagnetic type. Complex 2 shows field-induced single-molecule-magnetic
behavior. Impedance analysis shows that the proton conductivity of both complexes
reaches up to the maximum value of 4.7 * 10-4 S cm-1 for 1 and 9.06 * 10-5 S cm-1
for 2 at high temperature (>75 degrees C) and relative humidity (RH; 95%). The
Monte Carlo simulations confirm the exact location of the adsorbed water
molecules in the framework after humidification (RH = 95%) for 1. Further, the
results from computational simulation also reveal that the presence of a more
dense arrangement of adsorbed water molecules through hydrogen bonding in a
particular type of channel (along the a axis) contributes more to the proton
migration compared to the other channel (along the b axis) in the framework.
PMID- 28426210
TI - Tellurium Distribution and Speciation in Contaminated Soils from Abandoned Mine
Tailings: Comparison with Selenium.
AB - The distribution and chemical species of tellurium (Te) in contaminated soil were
determined by a combination of microfocused X-ray fluorescence (MU-XRF), X-ray
diffraction (MU-XRD), and X-ray absorption fine structure (MU-XAFS) techniques.
Results showed that Te was present as a mixture of Te(VI) and Te(IV) species,
while selenium (Se) was predominantly present in the form of Se(IV) in the soil
contaminated by abandoned mine tailings. In the contaminated soil, Fe(III)
hydroxides were the host phases for Se(IV), Te(IV), and Te(VI), but Te(IV) could
be also retained by illite. The difference in speciation and solubility of Se and
Te in soil can result from different structures of surface complexes for Se and
Te onto Fe(III) hydroxides. Furthermore, our results suggest that the retention
of Te(IV) in soil could be relatively weaker than that of Te(VI) due to
structural incorporation of Te(VI) into Fe(III) hydroxides. These findings are of
geochemical and environmental significance for better understanding the
solubility, mobility, and bioavailability of Te in the surface environment. To
the best of our knowledge, this is the first study reporting the speciation and
host phases of Te in field soil by the MU-XRF-XRD-XAFS techniques.
PMID- 28426211
TI - Dry Particulate Nitrate Deposition in China.
AB - A limited number of ground measurements of dry particulate nitrate deposition
(NO3-) makes it difficult and challenging to fully know the status of the spatial
and temporal variations of dry NO3- depositions over China. This study tries to
expand the ground measurements of NO3- concentrations at monitoring sites to a
national scale, based on the Ozone Monitoring Instrument (OMI) NO2 columns, NO2
profiles from an atmospheric chemistry transport model (Model for Ozone and
Related chemical Tracers, version 4, MOZART-4) and monitor-based sources, and
then estimates the NO3- depositions on a regional scale based on an inferred
model. The ground NO2 concentrations were first derived from NO2 columns and the
NO2 profiles, and then the ground NO3- concentrations were derived from the
ground NO2 concentrations and the relationship between NO2 and NO3- based on
Chinese Nationwide Nitrogen Deposition Monitoring Network (NNDMN). This estimated
dry NO3- depositions over China will be helpful in determining the magnitude and
pollution status in regions without ground measurements, supporting the
construction plan of environmental monitoring in future.
PMID- 28426212
TI - Construction of beta-Trifluoromethyl Enol Ether via Base-Promoted C-O Coupling
and Rearrangement of Hydrogen Atom.
AB - A novel, high-efficiency and high-selectivity construction of beta
trifluoromethyl enol ether via base-induced/promoted C-O coupling of
trifluoromethylated vinyl chloride and phenols is presented with a broad
substrate scope. The reaction mechanism, especially the significantly high
selectivity, was excavated and understood via DFT calculation and is well
supported by the experimental observation.
PMID- 28426213
TI - Role of Mediator and Effects of Temperature on ortho-C-N Bond Fusion Reactions of
Aniline Using Ruthenium Templates: Isolation and Characterization of New
Ruthenium Complexes of the in-Situ-Generated Ligands.
AB - In this work, ortho-C-N bond fusion reactions of aniline are followed by the use
of two different ruthenium mediators. Reaction of aniline with [RuIII(terpy)Cl3]
(terpy = 2,2':6',2"-terpyridine) resulted in a trans bis-aniline ruthenium(II)
complex [1]+ which upon oxidation with H2O2 produced compound [2]+ of a bidentate
ligand, N-phenyl-1,2-benzoquinonediimine, due to an oxidative ortho-C-N bond
fusion reaction. Complex [1]+ and aniline (neat) at 185 degrees C produced a bis
chelated ruthenium complex (3). A previously reported complex [RuII(N-phenyl-1,2
benzoquinonediimine)(aniline)2(Cl)2] (5) undergoes similar oxidation by air at
185 degrees C to produce complex [3]. A separate chemical reaction between
aniline and strongly oxidizing tetra-n-propylammonium perruthenate [(n
pr)4N]+[RuO4]- in air produced a ruthenium complex [4] of a N4
tetraamidophenylmacrocycle ligand via multiple ortho-C-N bond fusion reaction.
Notably, the yield of this product is low (5%) at 100 degrees C but increases to
25% in refluxing aniline. All these complexes are characterized fully by their
physicochemical characterizations and X-ray structure determination. From their
structural parameters and other spectroscopic studies, complex [2]+ is assigned
as [RuII(terpy)(N-phenyl-1,2-benzoquinonediimine)(Cl)]+ whereas complex [4] is
described as a ruthenium(VI) complex comprised of a reduced deprotonated N-phenyl
1,2-diamidobenzene and N4-tetraamidophenylmacrocyclic ligand. Complex [2]+
exhibits one reversible oxidation at 1.32 V and one reversible reduction at -0.75
V vs Ag/AgCl reference electrode. EPR of the electrogenerated complexes has
revealed that the oxidized complex is a ruthenium(III) complex with an axial EPR
spectrum at gav= 2.06. The reduced complex [2], on the other hand, shows a single
line EPR signal at gav= 1.998. In contrast, complex [4] shows two successive one
electron oxidation waves at 0.5 and 0.8 V and an irreversible reduction wave at
0.9 V. EPR studies of the oxidized complexes [4]+ and [4]2+ reveal that
oxidations are ligand centered. DFT calculations were employed to elucidate the
electronic structures as well as the redox processes associated with the above
complexes. Aerial ortho-C-N bond fusion reactions of aniline using two different
mediators, viz. [RuIII(terpy)Cl3] and [(n-pr)4N]+[RuO4]-, have been followed. It
is found that in the case of oxidizable Ru(III) mediator complex, C-N bond fusion
is limited only to dimerization reaction whereas the high-valent Ru(VII) salt
mediates multiple C-N bond fusion reactions leading to the formation of a novel
tetradentate N4-tetraamidophenylmacrocyclic ligand. Valence ambiguity in the
complexes of the resultant redox-active ligands is scrutinized.
PMID- 28426214
TI - Calix[5]arene Through-the-Annulus Threading of Dialkylammonium Guests Weakly
Paired to the TFPB Anion.
AB - Through-the-annulus threading of calix[5]arene penta-O-ethers by dialkylammonium
cations coupled to the loosely coordinating superweak TFPB- anion has been
achieved. 1H NMR titration data show that preorganization of the calix[5]arene
scaffold leads to great thermodynamic stability of the pseudorotaxane complexes
as well as to a favorable threading kinetic. Thus, calix[5]arene 1c, bearing tert
butyl groups at the wide rim, was threaded by all of the cations under study
(with the exception of the dibenzylammonium 2b+) more tightly than the other
derivatives under investigation (Ka's up to 2.02 +/- 0.2 * 105 M-1) because of
its preorganized cone conformation. According to DFT calculations, van der Waals
interactions between the tert-butyl groups of 1c and the alkyl chain of the
cationic axle are likely responsible for the remarkable stability observed. The
threading of the calix[5]arene wheels with the asymmetric pentylbenzylammonium
axle 2c+ led to the toposelective formation of the endo-pentylpseudorotaxane
stereoisomer in agreement with the known "endo-alkyl rule". Owing to the steric
hindrance of the axle phenyl group, the threading of the guest was seen to occur
in a unidirectional fashion through the calixarene narrow rim.
PMID- 28426215
TI - Five- and Six-Coordinated Silver(I) Complexes Derived from 2,6
(Pyridyl)iminodiadamantanes: Sustained Release of Bioactive Silver toward
Bacterial Eradication.
AB - Silver(I) complexes of two designed tridentate ligands, namely, 2,6
(pyridyl)iminoditriazaadamantane (pydTAm) and 2,6-(pyridyl)iminodiadamantane
(pydAm), have been synthesized and structurally characterized.
[Ag(pydTAm)2](CF3SO3) (1), the hitherto unknown mer isomer of a silver(I)
octahedral complex, crystallizes in a highly symmetric body-centered cubic I43m
space group. Quite in contrast, the AgI center in the analogous
[Ag(pydAm)2](CF3SO3) (2) complex resides in a trigonal-bipyramidal geometry and
crystallizes in a triclinic P1 space group with two crystallographically
independent molecules in the asymmetric unit. Complex 1 exhibits exceptional
solubility in aqueous media and leads to the efficient eradication of several
bacterial strains upon sustained release of bioactive silver.
PMID- 28426216
TI - Total Syntheses of Highly Oxidized ent-Kaurenoids Pharicin A, Pharicinin B, 7-O
Acetylpseurata C, and Pseurata C: A [5+2] Cascade Approach.
AB - The unprecedented oxidative dearomatization-induced [5+2] cycloaddition/pinacol
type 1,2-acyl migration cascade efficiently generates a quaternary carbon center
and assembles the highly oxygenated bicyclo[3.2.1]octane framework of ent-kaurene
diterpenoids. By incorporation of the subsequent retro-aldol/aldol process and
singlet oxygen ene reaction, this concise and convergent approach has enabled the
first asymmetric total syntheses of pharicin A, pharicinin B, 7-O-acetylpseurata
C, and pseurata C.
PMID- 28426217
TI - Phosphorus Depletion as a Green Alternative to Biocides for Controlling
Biodegradation of Metalworking Fluids.
AB - Metalworking fluids (MWFs) are used as lubricants and coolants in the
manufacturing operations. Their biodeterioration, while in operation, is a
widespread problem leading to poor performance and worker health issues. Adding
biocides, though effective in reducing microbial growth, leads to the production
of more recalcitrant wastewaters that are difficult to dispose or recycle on
site. Increasing environmental concerns have led to robust legislation for
reducing/eliminating the use of toxic biocides in MWFs, stimulating a growing
interest in the development/application of alternative biological preservation
strategies. In this study, inducing nutrient imbalance was investigated for
controlling microbial growth in MWFs. Phosphorus was immobilized employing
insoluble La2O3 to form LaPO4. Concentrations of La2O3 greater than 0.08%w (%w =
weight percent) completely inhibited microbial growth (from 1.4 * 107 to 0
CFU/mL) and hindered biodegradation. Raman spectroscopy suggested that La2O3
converted intracellular phosphorus into LaPO4. The growth inhibition potentials
of both 0.06%w La(NO3)3 and La2O3 were found to be superior to formaldehyde. The
antimicrobial property of La2O3 (i.e., inhibition) was tenable by adding
sufficient phosphate, acting as an on/off switch for controlling microbial growth
in MWFs. This technology offers the potential to reduce/eliminate the use of
biocides in MWFs, improves the feasibility of end-of-life biological treatment,
and closes the water loop.
PMID- 28426218
TI - The Excited-State Triple Proton Transfer Reaction of 2,6-Diazaindoles and 2,6
Diazatryptophan in Aqueous Solution.
AB - 3-Me-2,6-diazaindole ((2,6-aza)Ind) was strategically designed and synthesized to
probe water molecule catalyzed excited-state proton transfer in aqueous solution.
Upon electronic excitation (lambdamax ~ 300 nm), (2,6-aza)Ind undergoes N(1)-H to
N(6) long-distance proton transfer in neutral H2O, resulting in normal (340 nm)
and proton-transfer tautomer (480 nm) emissions with an overall quantum yield of
0.25. The rate of the water-catalyzed proton transfer shows a prominent H/D
kinetic isotope effect, which is determined to be 8.3 * 108 s-1 and 4.7 * 108 s-1
in H2O and D2O, respectively. Proton inventory experiments indicate the
involvement of two water molecules and three protons, which undergo a relay type
of excited-state triple proton transfer (ESTPT) in a concerted, asynchronous
manner. The results demonstrate for the first time the fundamental of triple
proton transfer in pure water for azaindoles as well as pave a new avenue for 2,6
diazatryptophan, an analogue of tryptophan exhibiting a similar ESTPT property
with (2,6-aza)Ind, to probe biowaters in proteins.
PMID- 28426219
TI - Solution-Processed Cesium Hexabromopalladate(IV), Cs2PdBr6, for Optoelectronic
Applications.
AB - Lead halide perovskites are materials with excellent optoelectronic and
photovoltaic properties. However, some hurdles remain prior to commercialization
of these materials, such as chemical stability, phase stability, sensitivity to
moisture, and potential issues due to the toxicity of lead. Here, we report a new
type of lead-free perovskite related compound, Cs2PdBr6. This compound is
solution processable, exhibits long-lived photoluminescence, and an optical band
gap of 1.6 eV. Density functional theory calculations indicate that this compound
has dispersive electronic bands, with electron and hole effective masses of 0.53
and 0.85 me, respectively. In addition, Cs2PdBr6 is resistant to water, in
contrast to lead-halide perovskites, indicating excellent prospects for long-term
stability. These combined properties demonstrate that Cs2PdBr6 is a promising
novel compound for optoelectronic applications.
PMID- 28426220
TI - Fluorescent Neuraminidase Assay Based on Supramolecular Dye Capture After
Enzymatic Cleavage.
AB - A conceptually new type of enzymatic cleavage assay is reported that utilizes in
situ supramolecular capture of the fluorescent product. A squaraine-derived
substrate with large blocking groups at each end of its structure cannot be
threaded by a tetralactam macrocycle until the blocking groups are removed by
enzyme cleavage. A prototype design responds to viral neuraminidase, an indicator
of influenza infection, and also measures susceptibility of the sample to
neuraminidase inhibitor drugs. The substrate structure incorporates three key
features: (a) a bis(4-amino-3-hydroxyphenyl)squaraine core with bright deep-red
fluorescence and excellent photostability, (b) an N-methyl group at each end of
the squaraine core that ensures fast macrocycle threading kinetics, and (c)
sialic acid blocking groups that prevent macrocycle threading until they are
removed by viral neuraminidase. The enzyme assay can be conducted in aqueous
solution where dramatic colorimetric and fluorescence changes are easily observed
by the naked eye. Alternatively, affinity capture beads coated with macrocycle
can be used to immobilize the liberated squaraine and enable a range of
heterogeneous analysis options. With further optimization, this new type of
neuraminidase assay may be useful in a point of care clinic to rapidly diagnose
influenza infection and also determine which of the approved antiviral inhibitor
drugs is likely to be the most effective treatment for an individual patient. The
assay design is generalizable and can be readily modified to monitor virtually
any type of enzyme-catalyzed cleavage reaction.
PMID- 28426221
TI - Charge Transport in Nanostructured Materials: Implementation and Verification of
Constrained Density Functional Theory.
AB - The in silico design of novel complex materials for energy conversion requires
accurate, ab initio simulation of charge transport. In this work, we present an
implementation of constrained density functional theory (CDFT) for the
calculation of parameters for charge transport in the hopping regime. We verify
our implementation against literature results for molecular systems, and we
discuss the dependence of results on numerical parameters and the choice of
localization potentials. In addition, we compare CDFT results with those of other
commonly used methods for simulating charge transport between nanoscale building
blocks. We show that some of these methods give unphysical results for thermally
disordered configurations, while CDFT proves to be a viable and robust approach.
PMID- 28426222
TI - Structural and Dynamical Properties of Tetraalkylammonium Bromide Aqueous
Solutions: A Molecular Dynamics Simulation Study Using a Polarizable Force Field.
AB - Understanding the behavior of aqueous solutions containing tetraalkylammonium
(TAA) cations is of great significance in a number of applications, including
polymer membranes for fuel cells. In this work, a polarizable force field has
been used to perform atomistic molecular dynamics (MD) simulations of aqueous
solutions containing tetramethylammonium (TMA) or tetrabutylammonium (TBA)
cations and Br counterions. Extensive MD simulations of TMA-Br/water and TBA
Br/water systems were conducted as a function of solution composition (ion
pair:water molar ratios of 1:10, 1:20, 1:30, 1:63, and 1:500) at atmospheric
pressure and 298 K. Our simulations demonstrate excellent agreement with
available experimental data for solution densities and diffusion coefficients of
different species as a function of solution composition, providing us confidence
in analyzed structural and dynamic correlations. Various ion-ion and ion-water
spatial distributions and the extent of cation aggregation are discussed in light
of changes in the structure of cations hydration shells. The delicate balance
between cation ionic core interactions with water and the hydrophobic
interactions of alkyl tails leads to nontrivial self-assembly of TAA cations and
the formation of an interpenetrating cationic network at higher concentrations.
The ions and water dynamics are strongly coupled with the observed structural
correlations and are analyzed in terms of various residence time, diffusion
coefficients, and ionic conductivity.
PMID- 28426223
TI - Over-Destabilization of Protein-Protein Interaction in Generalized Born Model and
Utility of Energy Density Integration Cutoff.
AB - The generalize Born (GB) model is frequently used in MD simulations of
biomolecular systems in aqueous solution. The GB model is usually based on the so
called Coulomb field approximation (CFA) for the energy density integration. In
this study, we report that the GB model with CFA overdestabilizes the long-range
electrostatic attraction between oppositely charged molecules (ionic bond forming
two-helix system and kinesin-tubulin system) when the energy density integration
cutoff, rmax, which is used to calculate the Born energy, is set to a large
value. We show that employing large rmax, which is usually expected to make
simulation results more accurate, worsens the accuracy so that the attraction is
changed into repulsion. It is demonstrated that the overdestabilization is caused
by the overestimation of the desolvation penalty upon binding that originates
from CFA. We point out that the overdestabilization can be corrected by employing
a relatively small cutoff (rmax = 10-15 A), affirming that the GB models, even
with CFA, can be used as a powerful tool to theoretically study the protein
protein interaction, particularly on its dynamical aspect, such as binding and
unbinding.
PMID- 28426225
TI - Quantum Design of pi-Electron Ring Currents in Polycyclic Aromatic Hydrocarbons:
Parallel and Antiparallel Ring Currents in Naphthalene.
AB - Control of pi-electrons in polycyclic aromatic hydrocarbons (PAHs) is one of the
fundamental issues in optoelectronics for ultrafast optical switching devices. We
have proposed an effective scenario for design of the generation of coherent ring
currents in naphthalene (D2h), which is the smallest unit of planar PAHs. It has
been demonstrated by using quantum chemical calculations and quantum optimal
control (QOC) simulations that two types of ring currents, parallel and
antiparallel, can be generated by resonance excitations by two linearly polarized
lasers. A parallel (antiparallel) ring current means that the currents of two
benzene rings run in the same (opposite) directions. The two types of ring
currents may be experimentally identified by magnetic force microscopy. The QOC
simulations indicate that a parallel ring current can be generated by using
continuous wave and Gaussian pulse lasers with their time delay without relying
on a sophisticated experimental apparatus. The present results provide a guiding
principle of coherent pi-electronics in PAHs for next-generation organic optical
switching devices.
PMID- 28426224
TI - Quantitative Analysis of Polymer Brush Formation Kinetics Using Quartz Crystal
Microbalance: Viscoelasticity of Polymer Brush.
AB - Polymer brush formation kinetics was measured by quartz crystal microbalance
(QCM). In the QCM measurement anomalous complex frequency shift as a function of
graft density was observed: dissipation rate shift DeltaGamma first increased,
showed a peak, and then decreased despite the graft density of the polymer brush
was increasing monotonically. We calculated the shear modulus of the brush layer
from the measured complex frequency shift and revealed that the peak of
DeltaGamma described the crossover from a viscous brush layer to elastic brush
layer. The crossover for the poly(ethylene glycol) with a molecular weight of
2000 occurs at around the characteristic graft density of 0.17 chains/nm2 which
was revealed from the structure analysis by surface plasmon resonance (SPR) and
neutron reflectivity (NR).
PMID- 28426226
TI - Brain Uptake of Bioactive Flavones in Scutellariae Radix and Its Relationship to
Anxiolytic Effect in Mice.
AB - Scutellariae Radix (SR) and its bioactive flavones elicit a variety of effects in
the brain. However, the brain uptake of individual SR flavones and its
relationship to the elicited effects after SR administration remain unknown.
Moreover, previous studies seldom measured pharmacokinetic and pharmacodynamic
outcomes simultaneously. In the current study, the brain uptake of six major SR
flavones and the anxiolytic behavior following oral administration of a SR
extract at two clinically relevant doses (600 and 1200 mg/kg twice daily) were
simultaneously investigated in mice (n = 18 per group). Brain and plasma
concentrations of the flavones were measured by LC-MS/MS, while the anxiolytic
effect was evaluated using the elevated plus maze. To further investigate the
mechanism behind the differential brain uptake of the six SR flavones, these
flavones were separately administered to mice at an equivalent molar oral dose (n
= 6). The brain tissue bindings of the SR flavones were also measured with the in
vitro brain slice method. Our results indicated that all six SR flavones
including three aglycons (baicalein, wogonin, and oroxylin A) and three
glucuronides (baicalin, wogonoside, and oroxyloside) could pass through the blood
brain barrier, with brain concentrations ranging from 7.9 to 224.0 pmol/g. It
provided novel evidence that oroxylin A had the highest brain uptake among the
six SR flavones regardless of its limited content in SR extract, in which 3.6
3.9% of the administered oroxylin A dose was present in the brain 6 h postdosing
and with a brain-to-plasma ratio of 0.42-0.46. Although SR extract contains
flavones that are positive modulators of the benzodiazepine binding site of GABAA
receptors (baicalein, wogonin, and baicalin), our behavioral study for the first
time indicated that SR extract (a mixture of six flavones) did not elicit
significant anxiolytic effect at the studied doses. Oroxylin A also demonstrated
the highest brain uptake when the six flavones were separately administered to
mice, and the highest affinity to brain tissues in the in vitro tissue binding
assay. The high brain uptake of oroxylin A, a GABAA antagonist which had been
reported to antagonize diazepam-induced anxiolytic effect, might have suppressed
the anxiolytic effects of the other flavones and account for the lack of overall
anxiolytic effect of SR extract. The current study illustrates the importance of
monitoring pharmacokinetics in a behavioral study, particularly for herbal
medicines which consist of multiple components that might have different or even
opposite pharmacological effects on the same target.
PMID- 28426227
TI - Monovalent versus Divalent Cation Diffusion in Thiospinel Ti2S4.
AB - Diffusion coefficients (D) for both Li+ and Mg2+ in Ti2S4 were measured using the
galvanic intermittent titration technique (GITT) as a function of both ion
concentration (x) and temperature. During discharge at 60 degrees C, DLi
descends gradually from 2 * 10-8 cm2/s at xLi ~ 0 to 2 * 10-9 cm2/s at xLi ~ 1.9.
In contrast, DMg decreases sharply from 2 * 10-8 to 1 * 10-12 cm2/s by xMg ~ 0.8.
This kinetic factor limits the maximum practical discharge capacity of MgxTi2S4.
The difference in behavior vis a vis Li+ implies that either increasing Mg2+
occupation of the tetrahedral site at xMg > 0.6 and/or interactions between
diffusing cations play a larger role in mediating the diffusion of divalent
compared to monovalent cations. Diffusion activation energies (Ea) extracted from
the temperature-dependent data revealed that Ea,Mg (540 +/- 80 meV) is about
twice that of Ea,Li (260 +/- 50 meV), explaining the poorer electrochemical
performance of MgxTi2S4 at room temperature.
PMID- 28426228
TI - Ultrafast Dynamics of a Triazene: Excited-State Pathways and the Impact of
Binding to the Minor Groove of DNA and Further Biomolecular Systems.
AB - Many synthetic DNA minor groove binders exhibit a strong increase in fluorescence
when bound to DNA. The pharmaceutical-relevant berenil (diminazene aceturate) is
an exception with an extremely low fluorescence quantum yield (on the order of 10
4). We investigate the ultrafast excited-state dynamics of this triazene by
femtosecond time-resolved fluorescence experiments in water, ethylene glycol, and
buffer and bound to the enzyme beta-trypsin, the minor groove of AT-rich DNA, and
G-quadruplex DNA. Ab initio calculations provide additional mechanistic insight.
The complementing studies unveil that the excited-state motion initiated by pipi*
excitation occurs in two phases: a subpicosecond phase associated with the
lengthening of the central N?N double bond, followed by a bicycle-pedal-type
motion of the triazene bridge, which is almost volume-conserving and can proceed
efficiently within only a few picoseconds even under spatially confined
conditions. Our results elucidate the excited-state relaxation mechanism of
aromatic triazenes and explain the modest sensitivity of the fluorescence quantum
yield of berenil even when it is bound to various biomolecules.
PMID- 28426229
TI - Nanofabricated Catalyst Particles for the Investigation of Catalytic Carbon
Oxidation by Oxygen Spillover.
AB - The catalytic oxidation of carbon by molecular oxygen was studied using C/Pt,
Pt/C, Pt/Al2O3/C, Pt/CeO2/C, Al2O3/C, and CeO2/C model samples prepared by hole
mask colloidal lithography. By this technique, the degree of contact between
platinum and carbon was controlled with high precision. The oxidation of carbon
was monitored using atomic force microscopy and scanning electron microscopy. The
results show that Pt in direct contact with carbon catalyzes the oxidation of
carbon by spillover of dissociated oxygen from Pt to carbon. By physically
separating Pt and carbon with a 10 nm thin spacer layer of Al2O3, the oxygen
spillover was entirely blocked. However, through a corresponding spacer layer of
CeO2, carbon oxidation was still observed, either by oxygen spillover from Pt to
carbon or directly dissociated on the ceria, although at a slower rate compared
to the case with no spacer layer between Pt and carbon.
PMID- 28426230
TI - Photophysics and Excited-State Properties of Cyclometalated Iridium(III)
Platinum(II) and Iridium(III)-Iridium(III) Bimetallic Complexes Bridged by
Dipyridylpyrazine.
AB - We investigated the electrochemical and excited-state properties of 2,3-bis(2
pyridyl)pyrazine (dpp)-bridged bimetallic complexes, (L)2Ir-dpp-PtCl [1, L = 2
(4',6'-difluorophenyl)pyridinato-N,C2 (dfppy); 2, L = 2-phenylpyridinato-N,C2
(ppy)] and [(L)2Ir]2(dpp) [3, L = dfppy; 4, L = ppy] compared to monometallic
complexes, (L)2Ir-dpp (5, L = dfppy; 6, L = ppy) and dpp-PtCl (dpp-PtIICl2; 7).
The single-crystal X-ray crystallographic structures of 1, 3, 5, and 6 showed
that 1 and 3 have approximately coplanar structures of the dpp unit, while the
noncoordinated pyridine ring of dpp in 5 and 6 is largely twisted with respect to
the pyrazine ring. We found that the properties of the bimetallic complex
significantly depended on the electronic and geometrical modulations of each
fragment: (1) electronic structure of the main L (C^N) ligand in an iridium
chromophore (L = dfppy or ppy) and (2) planarity of the bridging ligand (dpp).
Their electrochemical and photophysical properties revealed that efficient
electron-transfer processes predominated in the bimetallic systems regardless of
the second metal participation. The low efficiencies of photoluminescence of dpp
bridged Ir-Pt and Ir-Ir bimetallic complexes (1-4) could be explained by assuming
the involvement of crossing to platinum- and iridium-based d-d states from the
emissive state. Such stereochemical and electronic situations around dpp allowed
thermally activated crossing to platinum- and iridium-based d-d states from the
emissive triplet metal-to-ligand charge-transfer (3MLCT) state, followed by
cleavage of the dpp-Pt and (L)2Ir-dpp bonds. The transient absorption study
further confirmed that the planarity of the dpp bridging ligand, which was
defined as the magnitude of tilt between the pyridine ring and pyrazine, had a
direct correlation with the degree of nonradiative decay from the emissive
iridium-based 3MLCT to the Ir d-d or Pt d-d state, leading to photoinduced
dissociation of bimetallic complexes. From the dissociation pattern of metal
complexes analyzed after photoirradiation, we found that their dissociation
pathways were directly related to the quenching direction (either Ir d-d or Pt d
d) with a significant dependency on the relative 3MLCT levels of the (L)2Ir-dpp
component.
PMID- 28426231
TI - The Prevalence of Integrons as the Carrier of Antibiotic Resistance Genes in
Natural and Man-Made Environments.
AB - Class 1 integrase intI1 has been considered as a good proxy for anthropogenic
pollution because of being linked to genes conferring resistance to antibiotics.
The gene cassettes of class 1 integrons could carry diverse antibiotic resistance
genes (ARGs) and conduct horizontal gene transfer among microorganisms. The
present study applied high-throughput sequencing technique combined with an intI1
database and genome assembly to quantify the abundance of intI1 in 64
environmental samples from 8 ecosystems, and to investigate the diverse
arrangements of ARG-carrying gene cassettes (ACGCs) carried by class 1 integrons.
The abundance of detected intI1 ranged from 3.83 * 10-4 to 4.26 * 10 degrees
intI1/cell. High correlation (Pearson's r = 0.852) between intI1 and ARG
abundance indicated that intI1 could be considered as an important indicator of
ARGs in environments. Aminoglycoside resistance genes were most frequently
observed on gene cassettes, carried by 57% assembled ACGCs, followed by
trimethoprim and beta-lactam resistance genes. This study established the
pipeline for broad monitoring of intI1 in various environmental samples and
scanning the ARGs carried by integrons. These findings supplemented our knowledge
on the distribution of class 1 integrons and ARGs carried on mobile genetic
elements, benefiting future studies on horizontal gene transfer of ARGs.
PMID- 28426232
TI - Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa
H in Lipid Micelles.
AB - With the rise in antibiotic resistance, antimicrobial peptides (AMPs) show
promise for therapeutic development, but higher specificity is required. PGLa-H
is a naturally occurring decapeptide, reported to have moderate antibacterial
activity and low hemolytic activity, with its sequence being identical to that of
the C-terminal fragment of highly selective AMP, PGLa. DiPGLa-H, a sequential
tandem repeat of PGLa-H, and Kiadin, an analogue with a Val to Gly substitution
at position 15, display improved in vitro bactericidal activity against both Gram
negative and Gram-positive pathogens, with generally low toxicity for human
cells. Despite Gly being a more flexible residue, NMR structural studies showed
little difference in structure and dynamics between the two peptides for the
first 14 residues, with somewhat greater flexibility in the C-terminus of Kiadin
resulting in a tighter structure of the peptide in the presence of sodium dodecyl
sulfate micelles. AMPs found in organisms often exhibit minimal amino acid
mutations, and such small differences in peptide conformation may be utilized to
design more selective AMPs.
PMID- 28426233
TI - Investigation of Classical Organic and Ionic Liquid Cosolvents for Early-Stage
Screening in Fragment-Based Inhibitor Design with Unrelated Bacterial and Human
Dihydrofolate Reductases.
AB - Drug design by methods such as fragment screening requires effective
solubilization of millimolar concentrations of small organic compounds while
maintaining the properties of the biological target. We investigate four organic
solvents and three 1-butyl-3-methylimidazolium (BMIm)-based ionic liquids (ILs)
as cosolvents to establish conditions for screening two structurally unrelated
dihydrofolate reductases (DHFRs) that are prime drug targets. Moderate
concentrations (10%-15%) of cosolvents had little effect on inhibition of the
microbial type II R67 DHFR and of human DHFR (hDHFR), while higher concentrations
of organic cosolvents generally decreased activity of both DHFRs. In contrast, a
specific IL conserved the activity of one DHFR, while severely reducing the
activity of the other, and vice versa, illustrating the differing effect of ILs
on distinct protein folds. Most of the cosolvents investigated preserved the fold
of R67 DHFR and had little effect on binding of the cofactor NADPH, but reduced
the productive affinity for its substrate. In contrast, cosolvents resulted in
modest structural destabilization of hDHFR with little effect on productive
affinity. We conclude that the organic cosolvents, methanol, dimethylformamide,
and dimethylsulfoxide, offer the most balanced conditions for early-stage
compound screening as they maintain sufficient biological activity of both DHFRs
while allowing for compound dissolution in the millimolar range. However, IL
cosolvents showed poor capacity to solubilize organic compounds at millimolar
concentrations, mitigating their utility in early-stage screening. Nonetheless,
ILs could provide an alternative to classical organic cosolvents when low
concentrations of inhibitors are used, as when characterizing higher affinity
inhibitors.
PMID- 28426234
TI - The OTOGL p.Arg925* Variant is Associated with Moderate Hearing Loss in a Syrian
Nonconsanguineous Family.
AB - AIM: To screen for the genetic basis of congenital hearing loss in a Syrian
family. METHODS: A Syrian patient living in Lebanon presented with moderate
congenital hearing loss. The patient's large nonconsanguineous family was
recruited. DNA was extracted from blood samples and sent for whole-exome
sequencing. A detailed clinical examination along with audiograms was obtained
for all subjects. RESULTS: Hearing loss was noted to be mild to moderate in the
low and mid frequencies, sloping to moderate to severe in the high frequencies
for all affected members. Results of DNA analysis showed the presence of a
previously described p.Arg925* mutation in the OTOGL gene on both alleles in
affected family members, whereas nonaffected members either had the wild type or
one copy of the mutated allele. DISCUSSION: Mutations affecting the OTOGL gene
have been recently connected with nonsyndromic sensorineural hearing loss. Seven
such mutations have already been described. The p.Arg925* reported in this study
has been found once in a French family. The current report is the first to
describe this mutation in a Middle Eastern family.
PMID- 28426235
TI - Expressive social support buffers the impact of care-related work interruptions
on caregivers' depressive symptoms.
AB - OBJECTIVE: To assess if expressive and instrumental social support from family
and friends moderate the association of care-related work interruptions (e.g.
leaving work for the older adult's doctor appointment) with depressive symptoms
among working family caregivers of older adults. METHODS: Data were from the
Singapore Survey on Informal Caregiving (SSIC). A subsample of 662 dyads, each
comprising an older care-recipient [home-dwelling Singaporean aged 75 and older
receiving human assistance for at least one activity of daily living (ADL)] and
his/her working family caregiver, was analysed. Caregiver depressive symptoms
were assessed using the Center for Epidemiologic Studies Depression scale. Care
related work interruptions were scaled through the Mokken scaling procedure.
Expressive social support was assessed using a scale by Pearlin and co-workers.
Instrumental social support was based on the hours of ADL help provided to the
care-recipient by any family member or friend, on behalf of the primary
caregiver. A linear regression model, with interaction terms, assessed expressive
and instrumental social support as moderators of the association of care-related
work interruptions with caregiver depressive symptoms. RESULTS: More care-related
work interruptions were associated with more caregiver depressive symptoms. And,
this association was moderated by expressive, but not instrumental, social
support. CONCLUSION: Our findings conform to previous qualitative work suggesting
that caregivers' mental health may not benefit from instrumental support, but
from receiving expressive support instead. Initiatives for improving the care
experience of working caregivers of older adults should focus on promoting
expressive support from their friends and family.
PMID- 28426236
TI - RNA Extracted from Formalin-Fixed, Paraffin-Embedded Renal Biopsy Biospecimens:
An Evaluation of Alternative Extraction Kits and the Effects of Storage Time.
PMID- 28426237
TI - On the Complexity of Item Response Theory Models.
AB - Complexity in item response theory (IRT) has traditionally been quantified by
simply counting the number of freely estimated parameters in the model. However,
complexity is also contingent upon the functional form of the model. We examined
four popular IRT models-exploratory factor analytic, bifactor, DINA, and DINO
with different functional forms but the same number of free parameters. In
comparison, a simpler (unidimensional 3PL) model was specified such that it had 1
more parameter than the previous models. All models were then evaluated according
to the minimum description length principle. Specifically, each model was fit to
1,000 data sets that were randomly and uniformly sampled from the complete data
space and then assessed using global and item-level fit and diagnostic measures.
The findings revealed that the factor analytic and bifactor models possess a
strong tendency to fit any possible data. The unidimensional 3PL model displayed
minimal fitting propensity, despite the fact that it included an additional free
parameter. The DINA and DINO models did not demonstrate a proclivity to fit any
possible data, but they did fit well to distinct data patterns. Applied
researchers and psychometricians should therefore consider functional form-and
not goodness-of-fit alone-when selecting an IRT model.
PMID- 28426238
TI - Predictive Low-Glucose Suspend to Prevent Hypoglycemia.
PMID- 28426239
TI - Performance of an Artificial Pancreas System for Young Children with Type 1
Diabetes.
AB - BACKGROUND: Young children 5-8 years old with type 1 diabetes (T1D) exhibit clear
needs for improved glycemic control but may be limited in their ability to safely
interact with an artificial pancreas system. Our goal was to evaluate the safety
and performance of an artificial pancreas (AP) system among young children with
T1D. RESEARCH DESIGN AND METHODS: In a randomized, crossover trial, children with
T1D age 5-8 years were enrolled to receive on separate study periods (in random
order) either the UVa AP using the DiAs Control Platform software with child
resistant lock-out screens (followed as an out-patient admission) or their usual
insulin pump+continuous glucose monitor (CGM) care at home. Hypoglycemic events
and CGM tracings were compared between the two 68-h study periods. All analyses
were adjusted for level of physical activity as tracked using Fitbit devices.
RESULTS: Twelve participants (median age 7 years, n = 6 males) completed the
trial. Compared to home care, the AP admission resulted in increased time with
blood glucose (BG) 70-180 mg/dL (73% vs. 47%) and lower mean BG (152 mg/dL vs.
190 mg/dL), both P < 0.001 after adjustment for activity. Occurrence of
hypoglycemia was similar between sessions without differences in time <70 mg/dL
(AP 1.1% +/- 1.1%; home 1.6% +/- 1.2%). There were no adverse events during the
AP or home study periods. CONCLUSIONS: Use of an AP in young children was safe
and resulted in improved mean BG without increased hypoglycemia. This suggests
that AP use in young children is safe and improves overall diabetes control.
ClinicalTrials.gov registration number: NCT02750267.
PMID- 28426240
TI - Influence of Glenoid Defect Size and Bone Fragment Size on the Clinical Outcome
After Arthroscopic Bankart Repair in Male Collision/Contact Athletes.
AB - BACKGROUND: The usefulness of arthroscopic Bankart repair for collision/contact
athletes has varied in previous reports. PURPOSE: To investigate the influence of
glenoid rim morphologic characteristics on the clinical outcome after
arthroscopic Bankart repair without additional reinforcement procedures in male
collision/contact athletes, including athletes with a large glenoid defect. STUDY
DESIGN: Case-control study; Level of evidence, 3. METHODS: Eighty-six athletes
(93 shoulders) followed for a minimum of 2 years were retrospectively
investigated. The sports were rugby (36 shoulders), American football (29
shoulders), and other collision/contact sports (28 shoulders). Preoperative
glenoid defect size, bone fragment size, and bone union after bony Bankart repair
were investigated regarding factors influencing postoperative recurrence.
Postoperative changes in glenoid defect size and bone fragment size were
investigated as well as their influence on the clinical outcome. RESULTS:
Postoperative recurrence of instability was noted in 22 shoulders (23.7%). The
recurrence rate was 33.3% in rugby, 17.2% in American football, and 17.9% in
other collision/contact sports. The recurrence rate was only 7.1% in 28 shoulders
without a preoperative glenoid defect, but it increased to 43.8% in 16 shoulders
that did not have a bone fragment even though there was a preoperative glenoid
defect. Additionally, the recurrence rate was 7.7% in 26 shoulders with bone
union after arthroscopic bony Bankart repair but rose to 45% in 20 shoulders
without bone union. In the shoulders with bone union, the mean bone fragment size
increased from 8.2% preoperatively to 15.2% postoperatively, while the mean
glenoid defect size decreased from 18.0% to 2.8%, respectively. The recurrence
rate was 8.3% in shoulders with a final glenoid defect 5% or less versus 38.1% in
shoulders with a defect greater than 5%. While the recurrence rate was low among
athletes other than rugby players with a final defect of 10% or less, it was low
in only the rugby players with a defect of 0%. CONCLUSION: In male
collision/contact athletes, while the overall clinical outcome was
unsatisfactory, a favorable outcome was achieved in athletes without a
preoperative glenoid defect and athletes with bone union. The glenoid defect
decreased in size postoperatively due to remodeling of the united bone fragment,
and the recurrence rate was low when the final glenoid defect size was 5% or
less.
PMID- 28426241
TI - Extracellular Heme Uptake and the Challenge of Bacterial Cell Membranes.
AB - Iron is essential for the survival of most bacteria but presents a significant
challenge given its limited bioavailability. Furthermore, the toxicity of iron
combined with the need to maintain physiological iron levels within a narrow
concentration range requires sophisticated systems to sense, regulate, and
transport iron. Most bacteria have evolved mechanisms to chelate and transport
ferric iron (Fe3+) via siderophore receptor systems, and pathogenic bacteria have
further lowered this barrier by employing mechanisms to utilize the host's
hemoproteins. Once internalized, heme is cleaved by both oxidative and
nonoxidative mechanisms to release iron. Heme, itself a lipophilic and toxic
molecule, presents a significant challenge for transport into the cell. As such,
pathogenic bacteria have evolved sophisticated cell surface signaling and
transport systems to obtain heme from the host. In this review, we summarize the
structure and function of the heme-sensing and transport systems of pathogenic
bacteria and the potential of these systems as antimicrobial targets.
PMID- 28426242
TI - Cellular Electron Cryotomography: Toward Structural Biology In Situ.
AB - Electron cryotomography (ECT) provides three-dimensional views of macromolecular
complexes inside cells in a native frozen-hydrated state. Over the last two
decades, ECT has revealed the ultrastructure of cells in unprecedented detail. It
has also allowed us to visualize the structures of macromolecular machines in
their native context inside intact cells. In many cases, such machines cannot be
purified intact for in vitro study. In other cases, the function of a structure
is lost outside the cell, so that the mechanism can be understood only by
observation in situ. In this review, we describe the technique and its history
and provide examples of its power when applied to cell biology. We also discuss
the integration of ECT with other techniques, including lower-resolution
fluorescence imaging and higher-resolution atomic structure determination, to
cover the full scale of cellular processes.
PMID- 28426243
TI - Analysis of 2019 Patients Undergoing Revision Anterior Cruciate Ligament
Reconstruction From a Community-Based Registry.
AB - BACKGROUND: Knowledge of patient characteristics, surgical fixation, graft
choice, outcomes, and concurrent injuries of revision anterior cruciate ligament
reconstruction (ACLR) is limited. PURPOSE: To describe the current cohort of
revision ACLR captured by a community registry and the outcomes observed in the
registered patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
Patients who underwent revision ACLR registered between February 2005 and June
2014, by 200 surgeons in 46 hospitals, were evaluated. The Kaiser Permanente ACLR
Registry (KPACLRR) collected data intraoperatively and postoperatively using
paper forms, electronic medical records, administrative claims data, and patient
reported outcomes. The KPACLRR cohort was longitudinally followed, and outcomes
were prospectively ascertained. Outcomes (ie, revisions, subsequent operative
procedures, deep surgical site infections, and deep venous thrombosis) were
adjudicated via a chart review. Descriptive statistics were employed. RESULTS: Of
2019 patients who underwent revision ACLR, at a median follow-up of 2.2 years
(interquartile range, 1.0-3.8 years), 212 (10.5%) required subsequent operative
procedures, and 86 (4.3%) were revised a second time. At the time of revision,
55.1% of the patients had at least 1 concurrent meniscal injury, and 26% of those
were repairable. Cartilage injuries were present in 42.0% of patients. Deep
surgical site infections occurred in 12 patients (0.6%), deep venous thrombosis
occurred in 5 patients (0.3%), and 1 patient (0.1%) had a pulmonary embolism.
CONCLUSION: Revision ACLR can be performed with a low short-term revision rate
and relatively few complications. At the time of revision, nearly half of these
patients had an irreparable meniscal injury, and slightly less than half had a
cartilage injury. A large community-based ACLR registry is useful in informing
surgeons of current treatment practices, prevalence of concurrent injuries, and
outcomes associated with the procedures, especially infrequent procedures such as
revision ACLR.
PMID- 28426244
TI - Piperine Triggers Apoptosis of Human Oral Squamous Carcinoma Through Cell Cycle
Arrest and Mitochondrial Oxidative Stress.
AB - Piperine is a nitrogenous pungent substance exhibiting multifunctional
pharmacological properties. However, the mechanism underlying its anticancer
potential is not well elucidated in human oral squamous carcinoma (KB) cell line.
The anticancer potential of piperine was evaluated through potent biomarkers viz.
reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial
membrane potential (MMP). In addition, cell cycle kinetics and caspases-3
activity were also carried out to confirm anticancer activity of piperine.
Results showed that various concentrations (25-300 MUM) of piperine exposure
reduced the cell viability of KB cells significantly (P < 0.01). Piperine induced
significant (P < 0.01) dose-related increment in ROS production and nuclear
condensation. Moreover, piperine stimulated cell death by inducing loss of MMP,
and caspase-3 activation. Cell cycle study revealed that piperine arrested the
cells in G2/M phase and decreased the DNA content. Findings of this study suggest
the efficacy of piperine in inducing cell death via the decrease in MMP and ROS
liberation followed by caspase-3 activation and cell cycle arrest. Further
assessment of the anticancer potency of piperine is needed for anticancer drug
development.
PMID- 28426245
TI - Visualizing Tensions in an Ethnographic Moment: Images and Intersubjectivity.
AB - Images function as sources of data and influence our thinking about fieldwork,
representation, and intersubjectivity. In this article, I show how both the
ethnographic relationships and the working method of photography lead to a more
nuanced understanding of a healing event. I systematically analyze 33 photographs
made over a 15-minute period during the preparation and application of a poultice
(topical cure) in a rural Andean home. The images chronicle the event, revealing
my initial reaction and the decisions I made when tripping the shutter. By
unpacking the relationship between ethnographer and subject, I reveal the
constant negotiation of positions, assumptions, and expectations that make up
intersubjectivity. For transparency, I provide thumbnails of all images,
including metadata, so that readers may consider alternative interpretations of
the images and event.
PMID- 28426246
TI - Biofilm characteristics and evaluation of the sanitation procedures of
thermophilic Aeribacillus pallidus E334 biofilms.
AB - The ability of Aeribacillus pallidus E334 to produce pellicle and form a biofilm
was studied. Optimal biofilm formation occurred at 60 degrees C, pH 7.5 and 1.5%
NaCl. Extra polymeric substances (EPS) were composed of proteins and eDNA (21.4
kb). E334 formed biofilm on many surfaces, but mostly preferred polypropylene and
glass. Using CLSM analysis, the network-like structure of the EPS was observed.
The A. pallidus biofilm had a novel eDNA content. DNaseI susceptibility (86.8%
removal) of eDNA revealed its importance in mature biofilms, but the purified
eDNA was resistant to DNaseI, probably due to its extended folding outside the
matrix. Among 15 cleaning agents, biofilms could be removed with alkaline
protease and sodium dodecyl sulphate (SDS). The removal of cells from
polypropylene and biomass on glass was achieved with combined SDS/alkaline
protease treatment. Strong A. pallidus biofilms could cause risks for industrial
processes and abiotic surfaces must be taken into consideration in terms of
sanitation procedures.
PMID- 28426247
TI - Response to Letter on Immunoassays for Field Screening of Bacillus anthracis and
Ricin.
PMID- 28426248
TI - Variability in neurocognitive performance: Age, gender, and school-related
differences in children and from ages 6 to 12.
AB - Cognitive development in children presents peculiarities according to groups of
age, gender, and type of school. Few studies have been investigating the effects
of all these factors. The aim of this study was to investigate the main effects
and the interactions of age, gender, and type of school in 419 children from ages
6 to 12 years old evaluated by the Child Brief Neuropsychological Assessment
Battery (NEUPSILIN-Inf). Older children, children in private schools and girls
presented better results. Interactions between all three independent variables
were observed in different cognitive domains. The results highlight both the
heterogeneity and the influence of multiple factors in children's
neuropsychological development.
PMID- 28426249
TI - Non-Enzymatic Electrochemistry in Characterization and Analysis of Steroid
Compounds.
AB - This review summarizes achievements in electrochemistry-related research of
steroid-based compounds in clinical, pharmaceutical, and environmental analysis.
Special attention is paid to compounds possessing none or only isolated double
bonds at the steroid core. Their direct redox activity is limited to far
positive/negative potentials under variety of conditions and electrode materials
and relies on the functional groups attached to the steroid skeleton, or as the
case may be its double bond or moieties present at the side chain. The
possibilities of electroanalytical methods in sterol characterization and
analysis are demonstrated in a table with 31 references devoted to direct
voltammetric and amperometric methods of oxidation of cholesterol, phytosterols,
oxysterols, and related compounds at carbon-based and metal-based nanoparticles
modified electrodes, and the reduction of bile acids and their conjugates at
mercury-based electrodes, and modified glassy carbon electrodes. Furthermore,
methods based on the indirect oxidation of cholesterol using bromine species as a
mediator at platinum electrode and non-enzymatic cholesterol biosensors are
reviewed. Their drawbacks and benefits are discussed with respect to the
challenging task of identification and quantitation of these compounds in
biological matrices, otherwise mostly performed using expensive mass
spectrometric techniques preceded by a chromatographic separation step.
PMID- 28426250
TI - Processed Meat and Colorectal Cancer Risk: A Pooled Analysis of Three Italian
Case-Control Studies.
AB - To add evidence to the limited data available from southern Europe, we assessed
the association between processed meat consumption and colorectal cancer risk. We
analyzed data from three case-control studies conducted between 1985 and 2010 in
various Italian areas, including a total of 3745 incident cases and 6804 hospital
based controls. We calculated odds ratios (ORs) and 95% confidence intervals
(CIs) by unconditional multiple logistic regression models. The median
consumption of processed meat was around 20 g/day both in cases and controls. The
OR of colorectal cancer was 1.02 (95% CI 0.99-1.04) for an increase of 10 g/day
of processed meat. The association was statistically significant for colon cancer
(OR 1.03, 95% CI 1.00-1.06), particularly for proximal colon cancer (OR 1.09, 95%
CI 1.04-1.14), while there was no relation with rectal cancer (OR 0.99, 95% CI
0.95-1.03). The OR of proximal colon cancer was 1.38 (95% CI 1.08-1.75) for the
highest sex-specific tertile of consumption (>25 g/day for men, >21.5 for women)
compared with the lowest (<15 g/day), whereas no significant ORs were found for
other anatomical subsites. Our findings indicate that there is no association
with colorectal cancer overall, in the presence, however, of a positive
association with proximal colon cancer.
PMID- 28426251
TI - Current Concepts of the Anterolateral Ligament of the Knee: Anatomy,
Biomechanics, and Reconstruction.
AB - In 1879, Paul Segond described an avulsion fracture (now known as a Segond
fracture) at the anterolateral proximal tibia with the presence of a fibrous band
at the location of this fracture. Although references to this ligament were
occasionally made in the anatomy literature after Segond's discovery, it was not
until 2012 that Vincent et al named this ligament what we know it as today, the
anterolateral ligament (ALL) of the knee. The ALL originates near the lateral
epicondyle of the distal femur and inserts on the proximal tibia near Gerdy's
tubercle. The ALL exists as a ligamentous structure that comes under tension
during internal rotation at 30 degrees . In the majority of specimens, the ALL
can be visualized as a ligamentous structure, whereas in some cases it may only
be palpated as bundles of more tense capsular tissue when internal rotation is
applied. Biomechanical studies have shown that the ALL functions as a secondary
stabilizer to the anterior cruciate ligament (ACL) in resisting anterior tibial
translation and internal tibial rotation. These biomechanical studies indicate
that concurrent reconstruction of the ACL and ALL results in significantly
reduced internal rotation and axial plane tibial translation compared with
isolated ACL reconstruction (ACLR) in the presence of ALL deficiency. Clinically,
a variety of techniques are available for ALL reconstruction (ALLR). Current
graft options include the iliotibial (IT) band, gracilis tendon autograft or
allograft, and semitendinosus tendon autograft or allograft. Fixation angle also
varies between studies from full knee extension to 60 degrees to 90 degrees of
flexion. To date, only 1 modern study has described the clinical outcomes of
concomitant ALLR and ACLR: a case series of 92 patients with a minimum 2-year
follow-up. Further studies are necessary to define the ideal graft type, location
of fixation, and fixation angle for ALLR. Future studies also must be designed in
a prospective comparative manner to compare the clinical outcomes of patients
undergoing ACLR with ALL reconstruction versus without ALL reconstruction. By
discovering the true effect of the ALL, investigators can elucidate the
importance of ALLR in the setting of an ACL tear.
PMID- 28426252
TI - Intervention Effects on Stage of Change Membership and Transitions among
Adolescent Energy Balance Behaviors.
AB - The transition from childhood to adolescence is a crucial period for the
development of healthy behaviors to be sustained later in life. With obesity a
leading public health problem, the promotion of healthy behaviors has the
potential to make a huge impact. The current study evaluated Stage of Change
progression in a large (N = 4158) computer-delivered, Transtheoretical Model
tailored intervention focusing on physical activity and fruit and vegetable
consumption (FV). Markov models were used to explore stage transitions and
patterns of discrete change from sixth to ninth grade. Nested model comparisons
examined the consistency of these patterns across time and intervention
condition. Major findings supported models in which participants were free to
transition forward and backward to any of the stages, but higher probabilities
were observed for remaining in the same stage or for transitioning one or two
stages forward. Participants in the intervention group had higher probabilities
of transitioning toward Maintenance, with more change occurring relative to the
comparison group during transitions from grades six to eight but not for grades
eight to nine.
PMID- 28426253
TI - Using Computerized Mental Health Programs in Alternative Education: Understanding
the Requirements of Students and Staff.
AB - : Computerized cognitive behavioral therapy (cCBT) programs have been shown to be
both acceptable and effective with youth. However, their use with more vulnerable
youth, such as early school leavers, remains relatively unstudied. This study
explored student and staff attitudes toward the use of cCBT in an alternative
education setting. METHODS: Student and staff needs were assessed using the
Requirements development approach (Van Velsen, Wentzel, & Van Gemert-Pijnen,
2013). An online staff survey (n = 16) was conducted to provide information on
the context of delivery, and stakeholder requirements were further explored in
four student workshops (n = 32) and staff group discussions (n = 12). RESULTS:
Students' requirements in relation to program look and feel were reflective of
issues with literacy and concentration. Activity- rather than text-based programs
were considered easier to learn from, whereas attractive design with features
such as connecting with others were thought necessary to keep young people
engaged. Students wanted to learn practical skills on improving their mental
health and well-being, using content that is positive, encouraging, and credible
and that can be tailored to individual needs. Anonymity and voluntary
participation were considered essential when delivering cCBT in the context of
alternative education, as well as additional access from home to ensure
timeliness of support. Staff required both flexibility and careful planning and
timetabling in order to deliver cCBT in the alternative education setting and to
support student engagement. CONCLUSION: The findings provide novel insight into
the needs and preferences of vulnerable youth, with important implications for
the implementation of computerized mental health programs in alternative
education settings. A better understanding of user needs and preferences is
critical for improving the uptake and impact of e-mental health resources.
PMID- 28426254
TI - Naringin protects viscera from ischemia/reperfusion injury by regulating the
nitric oxide level in a rat model.
AB - We investigated the effects of naringin on small intestine, liver, kidney and
lung recovery after ischemia/reperfusion (I/R) injury of the gut. Rats were
divided randomly into four groups of eight. Group A was the sham control; group B
was ischemic for 2 h; group C was ischemic for 2 h and re-perfused for 2 h (I/R);
group D was treated with 50 mg/kg naringin after ischemia, then re-perfused for 2
h. Endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase
(iNOS) expressions were detected by immunolabeling. We also measured arginase
activity, amounts of nitric oxide (NO) and total protein. iNOS was increased
significantly in the small intestine, liver and kidney in group C. iNOS was
decreased significantly only in small intestine and lung in group D. eNOS was
increased significantly in the small intestine, liver and lung in group C. eNOS
was decreased in small intestine, liver and lung in group D; however, eNOS was
decreased in the kidney in group C and increased in the kidney in group D. The
amount of NO was decreased significantly in all tissues in group D, but arginase
activity was decreased in the small intestine and lung, increased in the kidney
and remained unchanged in the liver in group D. The total protein increased in
the small intestine and liver in group D, but decreased significantly in the
kidney and lung in group D. Naringin had significant, salutary effects on the
biochemical parameters of I/R by decreasing the NO level, equilibrating iNOS and
eNOS expressions, and decreasing arginase activity.
PMID- 28426255
TI - Pregabalin for the treatment of neuropathic pain: a narrative review for primary
care providers.
AB - BACKGROUND: Neuropathic pain (NeP) is a distinct type of pain caused by damage to
the nervous system itself. This often severe and chronic type of pain requires
specific treatments that target the underlying pain pathophysiology. AIM: The
purpose of the current narrative review is to provide an overview of pregabalin
(Lyrica 1 ) for the treatment of NeP including its effects on pain, pain-related
sleep interference, and other health-related outcomes, timing of therapeutic
effect, safety and tolerability, and dosing. The information provided here will
help primary care providers develop more effective NeP treatment strategies.
PMID- 28426256
TI - Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on
experimental wound healing.
AB - We investigated the wound healing efficacy of the Foeniculum vulgare compounds,
fenchone and limonene, using an excisional cutaneous wound model in rats. An
excision wound was made on the back of the rat and fenchone and limonene were
applied topically to the wounds once daily, separately or together, for 10 days.
Tissue sections from the wounds were evaluated for histopathology. The healing
potential was assessed by comparison to an untreated control group and an olive
oil treated sham group. We scored wound healing based on epidermal regeneration,
granulation tissue thickness and angiogenesis. After day 6, wound contraction
with limonene was significantly better than for the control group. Ten days after
treatment, a significant increase was observed in wound contraction and re
epithelialization in both fenchone and limonene oil treated groups compared to
the sham group. Groups treated with fenchone and with fenchone + limonene scored
significantly higher than the control group, but the difference was not
statistically significant compared to the olive oil treated group. Our findings
support the beneficial effects of fenchone and limonene for augmenting wound
healing. The anti-inflammatory and antimicrobial activities of fenchone and
limonene oil increased collagen synthesis and decreased the number of
inflammatory cells during wound healing and may be useful for treating skin
wounds.
PMID- 28426257
TI - Facial eschar following a single application of black salve.
AB - A previously healthy 86-year-old male was transported by ambulance to the trauma
bay of the emergency department (ED) for profuse bleeding from the left temple.
The ambulance crew raised concern that the volume and force of the bleed may
suggest arterial involvement. The patient reported having applied a natural
topical remedy to a mole two weeks prior at the recommendation of a naturopath.
The patient described progressive blackening and swelling of the area in the days
following the single application of the product. After gaining control of the
bleeding in the ED, the area was found to have a raised, 2 cm eschar.
PMID- 28426258
TI - Improvements in Out-of-Hospital Cardiac Arrest Survival from 1998 to 2013.
AB - OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) remains a major public health
burden. Aggregate OHCA survival to hospital discharge has reportedly remained
unchanged at 7.6% for almost 30 years from 1970 to 2008. We examined the trends
in adult OHCA survival over a 16-year period from 1998 to 2013 within a single
EMS agency. METHODS: Observational cohort study of adult OHCA patients treated by
Tualatin Valley Fire & Rescue (TVF&R) from 1998 to 2013. This is an ALS first
response fire agency that maintains an active Utstein style cardiac arrest
registry and serves a population of approximately 450,000 in 9 incorporated
cities in Oregon. Primary outcomes were survival to hospital discharge in all
patients and in the subgroup with witnessed ventricular fibrillation/pulseless
ventricular tachycardia (VF/VT). The impact of key covariates on survival was
assessed using univariate logistic regression. These included patient factors
(age and sex), event factors (location of arrest, witnessed status, and first
recorded cardiac arrest rhythm), and EMS system factors (response time interval,
bystander CPR, and non-EMS AED shock). We used multivariate logistic regression
to examine the impact of year increment on survival after multiple imputation for
missing data. Sensitivity analysis was performed with complete cases. RESULTS:
During the study period, 2,528 adult OHCA had attempted field resuscitation. The
survival rate for treated cases increased from 6.7% to 18.2%, with witnessed
VF/VT cases increasing from 14.3% to 31.4% from 1998 to 2013. Univariate analysis
showed that younger age, male sex, public location of arrest, bystander or EMS
witnessed event, initial rhythm of pulseless electrical activity (PEA) or VF/VT,
bystander CPR, non-EMS AED shock, and a shorter EMS response time were
independently associated with survival. After adjustment for covariates, the odds
of survival increased by 9% (OR 1.09, 95%CI: 1.05-1.12) per year in all treated
cases, and by 6% (OR 1.06, 95% 1.01-1.10) per year in witnessed VF/VT subgroups.
Findings remained consistent on sensitivity analysis. CONCLUSIONS: Overall
survival from treated OHCA has increased over the last 16 years in this
community. These survival increases demonstrate that OHCA is a treatable
condition that warrants further investigation and investment of resources.
PMID- 28426259
TI - The Sernbo score predicts 1-year mortality after displaced femoral neck fractures
treated with a hip arthroplasty.
AB - Background and purpose - Displaced femoral neck fractures (FNFs) are associated
with high rates of mortality during the first postoperative year. The Sernbo
score (based on age, habitat, mobility, and mental state) can be used to stratify
patients into groups with different 1-year mortality. We assessed this predictive
ability in patients with a displaced FNF treated with a hemiarthroplasty or a
total hip arthroplasty. Patients and methods - 292 patients (median age 83 (65
99) years, 68% female) with a displaced FNF were included in this prospective
cohort study. To predict 1-year mortality, we used a multivariate logistic
regression analysis including comorbidities and perioperative management. A
receiver operating characteristic (ROC) analysis was used to evaluate the
predictive ability of the Sernbo score, which was subsequently divided in a new
manner into a low, intermediate, or high risk of death during the first year.
Results - At 1-year follow-up, the overall mortality rate was 24%, and in
Sernbo's low-, intermediate-, and high-risk groups it was 5%, 22%, and 51%,
respectively. The Sernbo score was the only statistically significant predictor
of 1-year mortality: odds ratio for the intermediate-risk group was 4.2 (95% Cl:
1.5-12) and for the high-risk group it was 15 (95% CI: 5-40). The ROC analysis
showed a fair predictive ability of the Sernbo score, with an area under the
curve (AUC) of 0.79 (95% CI: 0.73-0.83). Using a cutoff of less than 11 points on
the score gave a sensitivity of 61% and a specificity of 83%. Interpretation -
The Sernbo score identifies patients who are at high risk of dying in the first
postoperative year. This scoring system could be used to better tailor
perioperative care and treatment in patients with displaced FNF.
PMID- 28426260
TI - The effects of intermittent use of the SGLT-2 inhibitor, dapagliflozin, in
overweight patients with type 2 diabetes in Japan: a randomized, crossover,
controlled clinical trial.
AB - BACKGROUND: This study examined the effects of short-term administration of the
sodium glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, on visceral fat
area (VFA) in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND
METHODS: In this randomized, crossover, controlled clinical trial, overweight
patients with type 2 diabetes were randomized to treatment with 5 mg
dapagliflozin for the first (n = 27) or second 12-week study period (n = 29). The
parameters evaluated at baseline and after 12 and 24 weeks included blood
pressure, hemoglobin A1c (HbA1c), body composition, VFA, and subcutaneous fat
area (SFA). RESULTS: In both groups, dapagliflozin administration improved the
levels of HbA1c, body weight, blood pressure, total fat mass, and VFA. Cessation
of dapagliflozin, however, reversed the improvements in HbA1c, blood pressure,
body weight, and SFA levels, whereas reductions in VFA and total fat mass levels
were somewhat maintained even after 12 weeks without treatment. CONCLUSIONS:
Dapagliflozin led to decreases in VFA and, consequently, body weight after a
short treatment period. However, these effects were largely reversed by the
cessation of dapagliflozin, suggesting that this agent should be administered
continuously to maintain clinical usefulness in overweight patients with type 2
diabetes.
PMID- 28426261
TI - A morphological study of uterine alterations in mice due to exposure to cadmium.
AB - We investigated the morphologic and molecular effects of exposure to cadmium (Cd)
for 30 and 60 days on the uteri of mice. We assessed uterine morphometric
measurements, eosinophilia, mast cell numbers, endometrial apoptosis,
proliferation and estrogen receptor alpha (ERalpha) immunoreactivity. We examined
vaginal smears that reflected the hormonal alterations in the female reproductive
tract. Because the female reproductive tract exhibits different morphology at
each stage of the estrous cycle, we sacrificed all animals at estrus to make
appropriate comparisons. Female BALB/c mice were exposed to 200 ppm Cd in their
drinking water for either 30 or 60 days. Cd exposure caused significant decreases
in endometrial thickness and number of glands in estrus phase uteri. The
endometrial eosinophilia in the groups exposed to Cd also decreased compared to
controls. Cd exposure increased the number of mast cells. Luminal and glandular
epithelia were examined using the terminal deoxynucleotidyl transferase dUTP nick
end labeling (TUNEL) assay and by immunostaining proliferating cell nuclear
antigen (PCNA) and estrogen receptor alpha (ERalpha). Compared to controls, the
apoptotic index increased with time in both Cd exposed groups, while the
proliferation index decreased. ERalpha immunoreactivity was decreased in both Cd
exposed groups compared to controls; the decrease was most apparent in the 30 day
Cd group. We found that 60 day Cd exposure increased apoptosis in the
endometrium, which may affect the receptivity of the uterus for implantation.
PMID- 28426262
TI - Feasibility of outpatient total hip and knee arthroplasty in unselected patients.
AB - Background and purpose - The number of patients who are suitable for outpatient
total hip and knee arthroplasty (THA and TKA) in an unselected patient population
remains unknown. The purpose of this prospective 2-center study was to identify
the number of patients suitable for outpatient THA and TKA in an unselected
patient population, to investigate the proportion of patients who were discharged
on the day of surgery (DOS), and to identify reasons for not being discharged on
the DOS. Patients and methods - All consecutive, unselected patients who were
referred to 2 participating centers and who were scheduled for primary THA and
TKA were screened for eligibility for outpatient surgery with discharge to home
on DOS. If patients did not fulfill the discharge criteria, the reasons
preventing discharge were noted. Odds factors with relative risk intervals for
not being discharged on DOS were identified while adjusting for age, sex, ASA
score, BMI and distance to home. Results - Of the 557 patients who were referred
to the participating surgeons during the study period, 54% were potentially
eligible for outpatient surgery. Actual DOS discharge occurred in 13-15% of the
557 patients. Female sex and surgery late in the day increased the odds of not
being discharged on the DOS. Interpretation - This study shows that even in
unselected THA and TKA patients, same-day discharge is feasible in about 15% of
patients. Future studies should evaluate safety aspects and economic benefits.
PMID- 28426263
TI - Using Contingent Reinforcement to Augment Muscle Activation After Perinatal
Brachial Plexus Injury: A Pilot Study.
AB - AIM: Examine the feasibility of increasing muscle activation with
electromyographically (EMG)-triggered musical-video as reinforcement for children
with perinatal brachial plexus injury (PBPI). METHODS: Six children with PBPI
(9.3 +/- 6.3 months; 5 female, 1 male) and 13 typically developing (TD) controls
(7.8 +/- 3.5 months; 4 female, 9 males) participated. The left arm was affected
in 5/6 children with PBPI. We recorded the integral (Vs) of biceps activation
with surface EMG during two conditions per arm in one session: (1) 100 second (s)
baseline without reinforcement and (2) 300 s reinforcement (musical-video
triggered to play with biceps activation above threshold [V]). We examined the
relation between the mean integral with reinforcement and hand preference.
RESULTS: Mean biceps activation significantly increased from baseline in the
affected arm of the group with PBPI by the 2nd (p < .008) and 3rd (p < .0004) 100
s intervals of reinforcement. Six of 6 children with PBPI and 12/13 TD controls
increased activation in at least one arm. A lower integral was linked with hand
preference for the unaffected right side in the PBPI group. CONCLUSION: This
study supports contingent reinforcement as a feasible method to increase muscle
activation. Future work will examine training dose and intensity to increase arm
function.
PMID- 28426264
TI - Differences between treatment-seeking and non-treatment-seeking participants in
medication studies for alcoholism: do they matter?
AB - BACKGROUND: Medication development for alcoholism typically includes experimental
pharmacology studies with non-treatment-seeking individuals with alcohol use
disorder (AUD) paving the way for randomized controlled trials in treatment
seekers with AUD. OBJECTIVES: The goal of this study is to provide a direct
comparison between AUD treatment-seeking research participants and non-treatment
seeking participants on demographic and clinical variables and to test whether
variables that differentiate the two groups are associated with clinical
outcomes. METHOD: Non-treatment-seeking AUD participants (n = 213; 76.3% male)
who completed behavioral pharmacology studies were compared to treatment-seekers
who completed the COMBINE Study (n = 1383; 69.1% male) on demographic and
clinical variables. Analyses examined whether the variables that differentiated
the two groups predicted treatment outcomes in the COMBINE Study. RESULTS:
Analyses revealed that treatment-seeking participants were older, had more years
of education, higher Alcohol Dependence Scale scores, higher Drinker Inventory of
Consequences scores, higher Obsessive Compulsive Drinking Scale scores, a greater
number of DSM-IV symptoms of AUD, longer duration of AUD, and consumed more
standard drinks and more drinks per drinking day (i.e., in the past 30 days)
compared to non-treatment-seeking participants. Nearly all characteristics that
differed between the groups predicted at least one of the primary clinical
outcomes of the COMBINE Study. CONCLUSIONS: This study highlights a host of
clinical and demographic factors that differ between non-treatment-seeking and
treatment-seeking research participants and the clinical significance of these
variables. Differences between samples should be considered and addressed in
order to promote greater consilience across stages of medication development.
PMID- 28426265
TI - Transdermal iontophoresis patch with reverse electrodialysis.
AB - Reverse electrodialysis (RED) technology generates energy from the salinity
gradient by contacting waters with different salinity. Herein, we develop the
disposable skin patch using this eco-friendly energy. The current density, which
can be controlled easily without special circuit, is enough to iontophoretic drug
delivery. In vitro study, this iontophoretic system enhanced the transdermal
delivery of peptide, which is difficult to penetrate the skin barrier by simple
diffusion. We design the disposable iontophoretic skin patch using RED system and
suggest this patch can be apply on new cosmetic patch or disposable drug patch.
PMID- 28426266
TI - Physicochemical Characteristics of the Seed and Seed Oil of the Potentially
Medicinal Plant Ziziphus oenoplia.
AB - The proximate composition of seeds, physicochemical characteristics, and fatty
acid profiles of Ziziphus oenoplia seed oil were determined in this study. The
seeds possessed low moisture (4.54%) and high carbohydrate (42.96%) and protein
content (40%), making the seed oil suitable for storage and consumption. The
saponification value (197.80) of the seed oil makes it a promising source for the
soap and shampoo industry. The iodine and saponification values are comparable to
those of major edible seed oils such as groundnut and soybean. The high amount of
monounsaturated fatty acids (53.41%), especially oleic acid (53.38%), present in
the oil makes it a better source for a low-fat diet and may reduce the risk of
various heart-related diseases.
PMID- 28426267
TI - A Phase-2 Trial of Single Agent Axitinib as Maintenance Therapy Following First
Line Treatment With Modified FOLFOX/Bevacizumab in Patients With Metastatic
Colorectal Cancer.
AB - This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for
patients with metastatic colorectal cancer (mCRC) following first-line treatment
with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed
by axitinib maintenance after four cycles. The primary endpoint was progression
free survival (PFS). Seventy patients were enrolled. Common treatment-related
toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during
FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral
neuropathy during axitinib treatment. Median PFS was 8.3 months. Treatment with
FOLFOX/bevacizumab followed by maintenance axitinib as first-line treatment for
mCRC produced a median PFS consistent with historical controls of other first
line regimens.
PMID- 28426268
TI - Putative Biomarkers of Response to Treatment in Breast Cancer Patients: A Pilot
Assay.
AB - Identifying tumor biomarkers associated with clinical behavior in breast cancer
patients may allow higher accuracy in the selection of treatment. Different types
of cells were determined in the primary tumors of stage I, II, and III of breast
cancer patients, who were assigned to one of the two groups: (1) disease-free or
(2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor
samples. CD4+ lymphocytes and CD44+CD24-/low cells (cancer stem cells) showed a
significant association with clinical outcome at 5 years of primary treatment,
while CD8+, Foxp3+, CD34+, and myeloid-derived suppressor cells did not show any
association. Coincident with the results of individual analysis, we identified
CD4+ cells and CD44+CD24-/low cells as good predictors of long-term clinical
outcome in a logistic regression.
PMID- 28426269
TI - 2016 International Orthoptic Congress Burian Lecture: Folklore or Evidence?
AB - The theme of the 2016 Burian Lecture is how our understanding of strabismus has
been changed by the research carried out in our laboratory in Reading over the
years. Accommodation and convergence are fundamental to orthoptics, but actual
responses have often been very different compared to what we had expected. This
paper outlines how our laboratory's understanding of common issues such as normal
development of accommodation and convergence, their linkage, intermittent
strabismus, anisometropia, orthoptic exercises, and risk factors for strabismus
have changed. A new model of thinking about convergence and accommodation may
help us to better understand and predict responses in our patients.
PMID- 28426270
TI - The Successful Treatment of Primary Cutaneous Localized Amyloidosis with a
Combined Therapy of Ablative Fractionated CO2 Laser,Topical Retinoid,
Corticosteroids and Levovitamin C: Five Cases with a Two-Year Follow Up.
PMID- 28426271
TI - Factors Associated with the Efficacy of Trigger Point Injection in Advanced
Cancer Patients.
AB - BACKGROUND: Few studies have reported the efficacy of trigger point injection
(TPI) to myofascial trigger points (MTrPs) in advanced cancer patients. Factors
that are associated with TPI efficacy have not yet been elucidated. OBJECTIVE:
The study was aimed at evaluating factors that are associated with TPI efficacy
to MTrPs in advanced cancer patients. DESIGN: Factors that are associated with
TPI efficacy were retrospectively identified based on a comparison between
clinically relevant responders and nonresponders by using multivariate regression
analysis. SETTING/SUBJECTS: One hundred five advanced cancer patients who visited
the Palliative Care Department with a chief complaint of pain and who received
TPI treatment to the MTrP at the pain site. RESULTS: The TPI efficacy rate on the
day after TPI treatment was 0.59 (95% confidence interval [CI]: 0.50-0.68).
Significant factors associated with TPI efficacy were coexistence of cancer pain
with MTrP at the pain site (odds ratio [OR]: 3.87, 95% CI: 1.21-12.4), MTrP at
areas other than lower back or hip (OR: 6.45, 95% CI: 1.98-21.0), and fewer MTrPs
(OR: 0.64, 95% CI: 0.42-0.99). Coexistence of cancer pain at the pain site of the
chief complaint was observed in 64% of study subjects (95% CI: 0.55-0.73).
CONCLUSIONS: The TPI efficacy is likely high when advanced cancer patients have
fewer MTrPs together with cancer pain at areas other than the lower back or hip.
MTrPs in advanced cancer patients are more commonly observed together with cancer
pain rather than independently. Healthcare providers should recognize the
relationship between MTrP and cancer pain and proactively perform physical
examinations to detect MTrPs for potential TPI.
PMID- 28426272
TI - Temperature-dependent regulation of rDNA condensation in Saccharomyces
cerevisiae.
AB - Chromatin condensation during mitosis produces detangled and discrete DNA
entities required for high fidelity sister chromatid segregation during mitosis
and positions DNA away from the cleavage furrow during cytokinesis. Regional
condensation during G1 also establishes a nuclear architecture through which gene
transcription is regulated but remains plastic so that cells can respond to
changes in nutrient levels, temperature and signaling molecules. To date,
however, the potential impact of this plasticity on mitotic chromosome
condensation remains unknown. Here, we report results obtained from a new
condensation assay that wildtype budding yeast cells exhibit dramatic changes in
rDNA conformation in response to temperature. rDNA hypercondenses in wildtype
cells maintained at 37 degrees C, compared with cells maintained at 23 degrees C.
This hypercondensation machinery can be activated during preanaphase but readily
inactivated upon exposure to lower temperatures. Extended mitotic arrest at 23
degrees C does not result in hypercondensation, negating a kinetic-based argument
in which condensation that typically proceeds slowly is accelerated when cells
are placed at 37 degrees C. Neither elevated recombination nor reduced
transcription appear to promote this hypercondensation. This heretofore
undetected temperature-dependent hypercondensation pathway impacts current views
of chromatin structure based on conditional mutant gene analyses and
significantly extends our understanding of physiologic changes in chromatin
architecture in response to hypothermia.
PMID- 28426273
TI - Preclinical development of BCG.HIVA2auxo.int, harboring an integrative expression
vector, for a HIV-TB Pediatric vaccine. Enhancement of stability and specific HIV
1 T-cell immunity.
AB - One of the critical issues that should be addressed in the development of a BCG
based HIV vaccine is genetic plasmid stability. Therefore, to address this issue
we have considered using integrative vectors and the auxotrophic mutant of BCG
complemented with a plasmid carrying a wild-type complementing gene. In this
study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid,
p2auxo.HIVAint, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector
uses an antibiotic resistance-free mechanism for plasmid selection and
maintenance. It was first transformed into a glycine auxotrophic E. coli strain
and subsequently transformed into a lysine auxotrophic Mycobacterium bovis BCG
strain to generate the vaccine BCG.HIVA2auxo.int. Presence of the HIVA gene
sequence and protein expression was confirmed. We demonstrated that the in vitro
stability of the integrative plasmid p2auxo.HIVAint was increased 4-fold, as
compared with the BCG strain harboring the episomal plasmid, and was genetically
and phenotypically characterized. The BCG.HIVA2auxo.int vaccine in combination
with modified vaccinia virus Ankara (MVA).HIVA was found to be safe and induced
HIV-1 and Mycobacterium tuberculosis-specific interferon-gamma-producing T-cell
responses in adult BALB/c mice. We have engineered a more stable and immunogenic
BCG-vectored vaccine using the prototype immunogen HIVA. Thus, the use of
integrative expression vectors and the antibiotic-free plasmid selection system
based on "double" auxotrophic complementation are likely to improve the
mycobacterial vaccine stability in vivo and immunogenicity to develop not only
recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens
but also other major pediatric pathogens to prime protective responses shortly
following birth.
PMID- 28426274
TI - A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su
or GSK1437173A) for varicella zoster virus.
AB - HZ/Su, branded as 'Shingrix', is one of the newest vaccines to be submitted for
multi-national regulatory approval. It is targeted to prevent shingles, a global
concern with aging populations. A live attenuated vaccine for shingles has been
available for over a decade, however it is contraindicated in specific subgroups
of people, and there are added concerns regarding long-term immunogenicity. HZ/Su
is the first subunit vaccine developed to protect against shingles. This paper
provides a critical appraisal of current evidence regarding HZ/Su.
PMID- 28426275
TI - Size does matter!
PMID- 28426276
TI - Integrative epigenetic and genetic pan-cancer somatic alteration portraits.
AB - Genetic and epigenetic alterations are required for carcinogenesis and the
mutation burden across tumor types has been investigated. Here, we investigate
epigenetic alterations with a novel measure of global DNA methylation
dysregulation, the methylation dysregulation index (MDI), across 14 cancer types
in The Cancer Genome Atlas (TCGA) database. DNA methylation data-obtained using
Illumina HumanMethylation450 BeadChip-was accessed from TCGA. We calculated the
MDI in 14 tumor types (n = 5,592 tumors), using adjacent normal tissues (n = 701)
from each tumor site. Copy number alteration, and mutation burden were retrieved
from cBioportal (n = 5,152). We tested the relation of subject MDI across tumors
and with age, gender, tumor stage, estimated tumor purity, and copy number
alterations for both overall MDI and genomic-context-specific MDI. We also
investigated the top most dysregulated loci shared across tumor types. There was
a broad range of extent in methylation dysregulation across tumor types (P < 2.2E
16). However, a consistent pattern of methylation dysregulation stratified by
genomic context was observed across tumor types where the highest dysregulation
occurred at non-CpG island regions. Considering other summary measures of somatic
alteration, MDI was correlated with copy number alterations but not with mutation
burden. Using the top dysregulated CpG sites in common across tumors, 4 classes
of cancer types were observed, and the functional consequences of these
alterations to gene expression were confirmed. This work identified the global
DNA methylation dysregulation patterns across 14 cancer types showing a higher
impact for the non-CpG island areas. The most dysregulated loci across cancer
types identified common clusters across cancer types that may have implications
for future treatment and prevention measures.
PMID- 28426277
TI - Topical Ganciclovir in Cytomegalovirus Anterior Uveitis.
AB - PURPOSE: To study the effects of topical ganciclovir 0.15% gel on cytomegalovirus
(CMV) anterior uveitis in a tertiary uveitis referral center in Brussels,
Belgium. METHODS: A retrospective study of patients with a clinical diagnosis of
CMV anterior uveitis/endotheliitis demonstrated by a positive polymerase chain
reaction and/or Goldmann-Witmer coefficient (GWc). RESULTS: We report a series of
15 patients presenting clinical characteristics of CMV anterior uveitis. Patients
had a pretreatment follow-up of 13.00 +/- 12.78 months and a posttreatment follow
up of 42.64 +/- 31.23 months. The 14 non-Asian patients (93.3%) had clinical
characteristics of Posner-Schlossman syndrome, and the only Asian patient (6.7%)
had keratic precipitates like Fuchs heterochromic iridocyclitis. At presentation,
uveitis was unilateral in all patients, visual acuity (VA) was 0.91 +/- 0.25, and
all patients had an increased intraocular pressure (IOP), with a mean IOP of
41.40 +/- 10.35 mmHg. At the end of the follow-up, 5 patients (33.3%) had
glaucoma, 2 needed glaucoma surgery (13.3%). The mean final VA was 0.93 +/- 0.11;
13 patients (86.5%) reached a final VA of 0.7 to 1. Patients had a significantly
lower number of recurrences/year posttreatment (0.76 +/- 0.57) than in the
pretreatment period (3.76 +/- 2.44) (P = 0.001). The mean time to recurrence
increased from 4.03 months before treatment to 12.58 months after treatment (P =
0.003). CONCLUSION: Our results suggest that patients treated with 0.15% topical
ganciclovir have a decreased frequency of CMV anterior uveitis recurrences, most
preserve a relatively good central vision over time. However, glaucoma is a
frequent and severe complication.
PMID- 28426278
TI - HOP3 a new regulator of the ER stress response in Arabidopsis with possible
implications in plant development and response to biotic and abiotic stresses.
AB - HOPs (heat shock protein 70 (HSP70)-heat shock protein 90 (HSP90) organizing
proteins) are a highly conserved family of cytosolic cochaperones. In a recent
study we showed that HOP3, a member of the HOP family in Arabidopsis, plays an
essential role during endoplasmic reticulum (ER) stress in plants. Interestingly,
we also demonstrated that AtHOP3 interacts with binding immunoglobulin protein
(BiP), a major ER-resident chaperone. All these data suggest that HOP3 could
assist BiP in protein folding in the ER. These findings open the exciting
possibility that HOP3, through its role in the alleviation of ER stress, could
play an important function during different developmental processes and in
response to different biotic and abiotic stresses.
PMID- 28426279
TI - Combination of gemcitabine and docetaxel regresses both gastric leiomyosarcoma
proliferation and invasion in an imageable patient-derived orthotopic xenograft
(iPDOX) model.
AB - Gastric leiomyosarcoma is a recalcitrant cancer and the chemotherapy strategy is
controversial. The present study used a patient-derived orthotopic xenograft
(PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective
therapeutic regimen to develop individualized precision medicine for this
disease. The gastric leiomyosarcoma obtained from a patient was first grown in
transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) to
stably label the tumor stroma. The RFP-expressing tumor was then passaged
orthotopically in the gastric wall of non-transgenic nude mice to establish an
imageable PDOX (iPDOX) model. The bright fluorescent tumor was readily imaged
over time to determine drug efficacy. Four weeks after implantation, 70 PDOX nude
mice were divided into 7 groups: control without treatment (n = 10); doxorubicin
(DOX) (2.4 mg/kg, intraperitoneally (i.p.), once a week for 2 weeks, n = 10);
gemcitabine (GEM)/ docetaxel (DOC) (GEM: 100 mg/kg, DOC: 20 mg/kg, i.p., once a
week for 2 weeks, n = 10); cyclophosphamide (CPA) (140 mg/kg, i.p., once a week
for 2 weeks, n = 10); temozolomide (TEM) (25 mg/kg, orally, daily for 14
consecutive days, n = 10); yondelis (YON) (0.15 mg/kg, i.v., once a week for 2
weeks, n = 10); pazopanib (PAZ) (100 mg/kg, orally, daily for 14 consecutive
days, n = 10). On day 14 from initiation of treatment, all treatments except PAZ
significantly inhibited tumor growth compared with untreated control (DOX: p <
0.01, GEM/DOC: p < 0.01, CPA: p < 0.01, TEM: p < 0.01, YON: p < 0.01) on day 14
after initiation. In addition, only GEM/DOC was more significantly effective than
DOX (p < 0.05). GEM/DOC could regress the leimyosarcoma in the PDOX model and has
important clinical potential for precision individual treatment of leiomyosarcoma
patients.
PMID- 28426280
TI - Alternative plant host defense against transposon activities occurs at the post
translational stage.
AB - The Antirrhinum DNA transposon Tam3 uniquely demonstrates low temperature
dependent transposition (LTDT), so transposition does not occur at high
temperatures. We previously showed that the detainment of Tam3 transposase
(TPase) at the plasma membrane occurs when transposition is inactive, and that
TPase is released at the permissive state of Tam3 transposition. LTDT of Tam3 is
attributed to interactions between Tam3 and its host. In this addendum, we
propose a model to explain the LTDT of Tam3, which is regarded as an equilibrium
state reached between the host and parasite to maximize the fitness of both.
PMID- 28426281
TI - Identification of SSEA-1 expressing enhanced reprogramming (SEER) cells in
porcine embryonic fibroblasts.
AB - Previous research has shown that a subpopulation of cells within cultured human
dermal fibroblasts, termed multilineage-differentiating stress enduring (Muse)
cells, are preferentially reprogrammed into induced pluripotent stem cells.
However, controversy exists over whether these cells are the only cells capable
of being reprogrammed from a heterogeneous population of fibroblasts. Similarly,
there is little research to suggest such cells may exist in embryonic tissues or
other species. To address if such a cell population exists in pigs, we
investigated porcine embryonic fibroblast populations (pEFs) and identified
heterogeneous expression of several key cell surface markers. Strikingly, we
discovered a small population of stage-specific embryonic antigen 1 positive
cells (SSEA-1+) in Danish Landrace and Gottingen minipig pEFs, which were absent
in the Yucatan pEFs. Furthermore, reprogramming of SSEA-1+ sorted pEFs led to
higher reprogramming efficiency. Subsequent transcriptome profiling of the SSEA
1+ vs. the SSEA-1neg cell fraction revealed highly comparable gene signatures.
However several genes that were found to be upregulated in the SSEA-1+ cells were
similarly expressed in mesenchymal stem cells (MSCs). We therefore termed these
cells SSEA-1 Expressing Enhanced Reprogramming (SEER) cells. Interestingly, SEER
cells were more effective at differentiating into osteocytes and chondrocytes in
vitro. We conclude that SEER cells are more amenable for reprogramming and that
the expression of mesenchymal stem cell genes is advantageous in the
reprogramming process. This data provides evidence supporting the elite theory
and helps to delineate which cell types and specific genes are important for
reprogramming in the pig.
PMID- 28426284
TI - Participatory Genomic Research: Ethical Issues from the Bottom Up to the Top
Down.
AB - Participatory approaches to genomic research manifest along a continuum from
bottom-up citizen-science initiatives designed to liberate scientific inquiry
from the constraints of traditional research institutional contexts and
professional practices to top-down investigator-initiated studies designed to
expose the public to scientific research processes and build its support and
enthusiasm for genomic research. With foundations as varied as open science,
crowdsourcing, patient advocacy, social media, the digitization of health, and
the neoliberalization of academic research, a range of ethical frameworks inform
the modes of participatory genomic research. Using illustrations from citizen
genomic science, patient advocacy, and investigator-led and government-initiated
genomic research efforts, we argue that as participatory genomic research pushes
the conventional research boundaries toward a more democratizing ethos, it
challenges scientific practices and the ethical conduct of genomic research both
within and outside of the traditional sites of biomedical innovation.
PMID- 28426282
TI - Emerging roles of macrosatellite repeats in genome organization and disease
development.
AB - Abundant repetitive DNA sequences are an enigmatic part of the human genome.
Despite increasing evidence on the functionality of DNA repeats, their biologic
role is still elusive and under frequent debate. Macrosatellites are the largest
of the tandem DNA repeats, located on one or multiple chromosomes. The
contribution of macrosatellites to genome regulation and human health was
demonstrated for the D4Z4 macrosatellite repeat array on chromosome 4q35. Reduced
copy number of D4Z4 repeats is associated with local euchromatinization and the
onset of facioscapulohumeral muscular dystrophy. Although the role other
macrosatellite families may play remains rather obscure, their diverse
functionalities within the genome are being gradually revealed. In this review,
we will outline structural and functional features of coding and noncoding
macrosatellite repeats, and highlight recent findings that bring these sequences
into the spotlight of genome organization and disease development.
PMID- 28426283
TI - Identification of the proteome complement of humanTLK1 reveals it binds and
phosphorylates NEK1 regulating its activity.
AB - The Tousled Like kinases (TLKs) are involved in numerous cellular functions,
including the DNA Damage Response (DDR), but only a handful of substrates have
been identified thus far. Through a novel proteomic screen, we have now
identified 165 human proteins interacting with TLK1, and we have focused this
work on NEK1 because of its known role in the DDR, upstream of ATR and Chk1. TLK1
and NEK1 were found to interact by coIP, and their binding is strengthened
following exposure of cells to H2O2. Following incubation with doxorubicin, TLK1
and NEK1 relocalize with nuclear repair foci along with gammaH2AX. TLK1
phosphorylated NEK1 at T141, which lies in the kinase domain, and caused an
increase in its activity. Following DNA damage, addition of the TLK1 inhibitor,
THD, or overexpression of NEK1-T141A mutant impaired ATR and Chk1 activation,
indicating the existence of a TLK1>NEK1>ATR>Chk1 pathway. Indeed, overexpression
of the NEK1-T141A mutant resulted in an altered cell cycle response after
exposure of cells to oxidative stress, including bypass of G1 arrest and
implementation of an intra S-phase checkpoint.
PMID- 28426285
TI - The Yin and Yang of Autism Genetics: How Rare De Novo and Common Variations
Affect Liability.
AB - The etiology of autism spectrum disorder (ASD) is complex, involving both genetic
and environmental contributions to individual and population-level liability.
Early researchers hypothesized that ASD arises from polygenic inheritance, but
later results, such as the identification of mutations in certain genes that are
responsible for syndromes associated with ASD, led others to propose that de novo
mutations of major effect would account for most cases. This yin and yang of
monogenic causes and polygenic inheritance continues to this day. The development
of genome-wide genotyping and sequencing techniques has resulted in remarkable
advances in our understanding of the genetic architecture of risk for ASD. The
combined research findings provide solid evidence that ASD is a complex polygenic
disorder. Rare de novo and inherited variations act within the context of a
common-variant genetic load, and this load accounts for the largest portion of
ASD liability.
PMID- 28426286
TI - On the Evolution of Lactase Persistence in Humans.
AB - Lactase persistence-the ability of adults to digest the lactose in milk-varies
widely in frequency across human populations. This trait represents an adaptation
to the domestication of dairying animals and the subsequent consumption of their
milk. Five variants are currently known to underlie this phenotype, which is
monogenic in Eurasia but mostly polygenic in Africa. Despite being a textbook
example of regulatory convergent evolution and gene-culture coevolution, the
story of lactase persistence is far from clear: Why are lactase persistence
frequencies low in Central Asian herders but high in some African hunter
gatherers? Why was lactase persistence strongly selected for even though milk
processing can reduce the amount of lactose? Are there other factors, outside of
an advantage of caloric intake, that contributed to the selective pressure for
lactase persistence? It is time to revisit what we know and still do not know
about lactase persistence in humans.
PMID- 28426287
TI - Pregnancy and the Acceptability of Computer-Based Versus Traditional Mental
Health Treatments.
AB - BACKGROUND: Recent recommendations urge increased depression screening in
pregnant and postpartum women, potentially increasing demand for treatment.
Computer-based psychotherapy treatments may address some of perinatal women's
unique mental health treatment needs and barriers. MATERIALS AND METHODS: We
conducted a quantitative survey of pregnant women (>=12 weeks of gestation) on
preferences regarding computer-based therapies compared with traditional
therapies (psychotherapy and medication). Nonpregnant women and men served as
comparison groups. Participants were provided descriptions of three computer
based therapies: video telehealth therapy (VTT), computer-assisted therapy (CAT),
and self-guided online therapy (SGO). Participants were asked to select all
options that they would consider for treatment as well as first choice
preference. The Patient Health Questionnaire-9 (PHQ-9) assessed current
depressive symptomatology, and the Mini International Neuropsychiatric Interview
(MINI) assessed psychiatric history. RESULTS: Participants included pregnant
females (n = 111), nonpregnant females (n = 147), and males (n = 54). Among
pregnant women, 77.5% (n = 86) indicated that they would consider some form of
computer-based therapy for mental health treatment during pregnancy; VTT was the
most commonly considered, followed by CAT and SGO. When asked to select their
preferred intervention, traditional talk therapy was the first choice among all
three groups, controlling for treatment history and PHQ-9 score. About one-third
of pregnant women chose some form of computer-based therapy as their top choice.
CONCLUSIONS: While computer-based therapies were acceptable to most pregnant
women in this sample, traditional talk therapy was the preferred option. Future
research should consider how to tailor computer-based therapies to the unique
needs of perinatal women.
PMID- 28426288
TI - Post translational modifications of Rab GTPases.
AB - Rab GTPases, the highly conserved members of Ras GTPase superfamily are central
players in the vesicular trafficking. They are critically involved in
intracellular trafficking pathway, beginning from formation of vesicles on donor
membranes, defining trafficking specificity to facilitating vesicle docking on
target membranes. Given the dynamic roles of Rabs during different stages of
vesicular trafficking, mechanisms for their spatial and temporal regulation are
crucial for normal cellular function. Regulation of Rab GTPase activity,
localization and function has always been focused in and around the association
of GDP dissociation inhibitor (GDI), Guanine nucleotide Exchange Factor (GEFs)
and GTPase accelerating protein (GAP) to Rabs. However, several recent studies
have highlighted the importance of different post-translational modifications in
regulation of Rab activation and function. This review provides a summary of
various post translational modifications (PTMs) and their significance to
regulate localization and function of different Rabs.
PMID- 28426289
TI - Injuries and exposures among ocean safety providers: A review of workplace
injuries and exposures from 2007-2012.
AB - Research on workplace injuries and exposures in ocean safety personnel remains
limited. Despite increasing beach attendance and reliance on lifeguards for
protection, the most common types of injuries, equipment resulting in injuries,
and environmental exposures remains unknown. This study reviewed OSHA 300 logs
summarizing workers' compensation claims from 2007-2012 to identify common body
parts injured, action at time of injury, equipment causing injury, and
environmental exposures. A secondary phase consisted of a cross-sectional
anonymous survey to determine demographics, body part injured, equipment causing
injury, sun and environmental exposures, action at time of injury, and proportion
of injuries reported to the department. During the 6-year period, 304 claims from
the OSHA logs were reviewed, finding the lower extremity was most commonly
injured with 2921 (31.9%) cumulative lost work days (104 reported injured, 34.2%)
followed by the back with 1679 (18.4%) lost work days (39 reported injuries,
12.8%). Of the 304 occupational injury claims from OSHA logs, 108 incidents
(35.5%) occurred during rescues, 87 (28.6%) during normal duties, and 31 (10.2%)
during training. Of survey participants, 22/52 sustained an injury, with 14
filling a worker's compensation claim. The rescueboard resulted in 7/22 injuries
(31.8%) while 17 (32.7%) of respondents sought care for a sun related concern
with a mean of 9.3 days lost. Occupational injuries in ocean safety personnel are
largely unknown. In this study, lower extremity and back injuries were the most
common musculoskeletal injuries providers encountered. Rescues and moving
equipment were common actions at the time of injury. With this preliminary
information, jurisdictions may develop training directed at rescue techniques and
safer options for moving heavy equipment.
PMID- 28426290
TI - Development of a thoracic personal sampler system for co-sampling of sulfuric
acid mist and sulfur dioxide gas.
AB - A novel personal sampler was designed to measure inorganic acid mists and gases
for determining human exposure levels to these acids in workplaces. This sampler
consists of (1) a parallel impactor for classifying aerosol by size following the
ISO/CEN/ACGIH defined human thoracic fraction, (2) a cellulose filter to collect
the residual acid mist but allowing penetration of sulfur dioxide gas, and (3) an
accordion-shaped porous membrane denuder (aPMD) for adsorbing the penetrating
sulfur dioxide gas. Acid-resistant PTFE was chosen as the housing material to
minimize sampling interference. To test the performance of the parallel impactor,
monodisperse aerosol was created by a vibrating orifice aerosol generator. The
results showed that the penetration curve of the impactor run at 2 LPM flow rate
agreed well with the defined thoracic fraction. Almost all sampling biases were
within 10% for particle size distributions with MMAD between 1-25 um and GSD
between 1.75-4, which meets the criteria of the EN 13205 standard. To evaluate
the performance of the aPMDs, sulfur dioxide gas was sourced directly from a
cylinder. The aPMDs maintained a gas collection efficiency greater than 95% for 4
hr when sampling 8.6 ppm of sulfur dioxide gas. While the aPMD had similar
performance to the commonly adopted annular or honeycomb denuders made of glass,
this shatterproof aPMD is only half of the volume and 1/25th the weight of the
honeycomb denuder. Testing of the entire sampler with a mixture of sulfuric acid
mist and sulfur dioxide gas showed the system could sample both with negligible
interference. All the test results illustrate that the new sampler, which is
flat, lightweight, and portable, is suitable for personal use and is capable of a
more accurate assessment of human exposure to inorganic acid mist and SO2 gas.
PMID- 28426291
TI - The Structure of Policy Networks for Injury and Violence Prevention in 15 US
Cities.
AB - OBJECTIVES: Changes in policy can reduce violence and injury; however, little is
known about how partnerships among organizations influence policy development,
adoption, and implementation. To understand partnerships among organizations
working on injury and violence prevention (IVP) policy, we examined IVP policy
networks in 15 large US cities. METHODS: In summer 2014, we recruited 15 local
health departments (LHDs) to participate in the study. They identified an average
of 28.9 local partners (SD = 10.2) working on IVP policy. In late 2014, we sent
survey questionnaires to 434 organizations, including the 15 LHDs and their local
partners, about their partnerships and the importance of each organization to
local IVP policy efforts; 319 participated. We used network methods to examine
the composition and structure of the policy networks. RESULTS: Each IVP policy
network included the LHD and an average of 21.3 (SD = 6.9) local partners. On
average, nonprofit organizations constituted 50.7% of networks, followed by
government agencies (26.3%), schools and universities (11.8%), coalitions
(11.2%), voluntary organizations (9.6%), hospitals (8.5%), foundations (2.2%),
and for-profit organizations (0.7%). Government agencies were perceived as
important by the highest proportion of partners. Perceived importance was
significantly associated with forming partnerships in most networks; odds ratios
ranged from 1.07 (95% CI, 1.02-1.13) to 2.35 (95% CI, 1.68-3.28). Organization
type was significantly associated with partnership formation in most networks
after controlling for an organization's importance to the network. CONCLUSIONS:
Several strategies could strengthen local IVP policy networks, including (1)
developing connections with partners from sectors that are not well integrated
into the networks and (2) encouraging indirect or less formal connections with
important but missing partners and partner types.
PMID- 28426292
TI - Efficacy of Three Different Lasers on Eradication of Enterococcus faecalis and
Candida albicans Biofilms in Root Canal System.
AB - OBJECTIVE: The objective was to compare the efficacy of three different lasers in
disinfection of root canals inoculated with Enterococcus faecalis and Candida
albicans biofilms. BACKGROUND: Endodontic space disinfection depends on the type
of root canal irrigant used and the way it is delivered and agitated because
irrigants have limited ability to reach all parts of root canal system. MATERIALS
AND METHODS: Thirty single-rooted human teeth were selected. Root canals were
instrumented and root surfaces were sealed using adhesive and the apical openings
with adhesive and composite resin. Roots were fixed in Eppendorf tubes and
sterilized in autoclave. The specimens were randomly divided into three
experimental groups (n = 10) and inoculated with E. faecalis and C. albicans.
After 7 days of incubation period, the number of E. faecalis and C. albicans
colony-forming units (CFUs) was determined for each root canal. In the first
experimental group, Er:YAG laser (0.3 W) with photon-induced photoacoustic
streaming technique was used for root canal disinfection, in the second, Nd:YAG
laser (1.5 W), and in the third, Er,Cr:YSGG (1.25 W) laser was used. After
different root canal disinfection protocols, the number of E. faecalis and C.
albicans CFUs was determined again for each root canal. RESULTS: Er:YAG and
Er,Cr:YSGG lasers eradicated significant number of E. faecalis and C. albicans
CFUs (p < 0.05), while Nd:YAG laser irradiation did not result in statistically
significant reduction (p > 0.05). Er,Cr:YSGG laser eradicated significantly more
microorganisms in comparison with Er:YAG laser (p < 0.05). CONCLUSIONS:
Er,Cr:YSGG laser was the most efficient tool in eradication of E. faecalis and C.
albicans biofilms.
PMID- 28426293
TI - Identifying thermal breakdown products of thermoplastics.
AB - Polymers processed to produce plastic articles are subjected to temperatures
between 150 degrees C and 450 degrees C or more during overheated processing and
breakdowns. Heat-based processing of this nature can lead to emission of volatile
organic compounds (VOCs) into the thermoplastic processing shop. In this study,
laboratory experiments, qualitative and quantitative emissions measurement in
thermoplastic factories were carried out. The first step was to identify the
compounds released depending on the thermoplastic nature, the temperature and the
type of process. Then a thermal degradation protocol that can extrapolate the
laboratory results to industry scenarios was developed. The influence of three
parameters on released thermal breakdown products was studied: the sample
preparation methods-manual cutting, ambient, or cold grinding-the heating rate
during thermal degradation-5, 10 20, and 50 degrees C/min-and the decomposition
method-thermogravimetric analysis and pyrolysis. Laboratory results were compared
to atmospheric measurements taken at 13 companies to validate the protocol and
thereby ensure its representativeness of industrial thermal processing. This
protocol was applied to most commonly used thermoplastics to determine their
thermal breakdown products and their thermal behaviour. Emissions data collected
by personal exposure monitoring and sampling at the process emission area show
airborne concentrations of detected compounds to be in the range of 0-3 mg/m3
under normal operating conditions. Laser cutting or purging operations generate
higher pollution levels in particular formaldehyde which was found in some cases
at a concentration above the workplace exposure limit.
PMID- 28426294
TI - The Interface Among Poverty, Air Mattress Industry Trends, Policy, and Infant
Safety.
AB - Infants can suffocate on air mattresses, even when the mattress is fully
inflated. The interfacing issues of poverty, the bedbug epidemic, and changes in
the design and marketing of air mattresses may be increasing consumer use of air
mattresses as primary sleep environments and thus increasing the potential for
infant death. Despite recent changes to improve air mattress safety labeling, the
National Child Death Review Case Reporting System found that between 2004 and
2015 across 24 states, an air mattress was the incident sleep place for 108
infants whose deaths were either during sleep or in a sleep environment. At the
same time, design components such as inflatable headboards and memory foam pillow
tops potentially increase the hazard to infants, and marketing changes represent
air mattresses as a preferred low-cost primary sleep environment. Analysis of
current data surveillance systems, published position statements, and consumer
materials from national organizations and federal agencies reveal opportunities
for changing policy to better protect infants from this hazard.
PMID- 28426297
TI - Note From the Editor-in-Chief: Who Wants to Exclude Older LGBT Persons From
Public Health Surveillance?
PMID- 28426296
TI - A Typical Day With Mild Cognitive Impairment.
PMID- 28426295
TI - Review of Recent Methodological Developments in Group-Randomized Trials: Part 1
Design.
AB - In 2004, Murray et al. reviewed methodological developments in the design and
analysis of group-randomized trials (GRTs). We have highlighted the developments
of the past 13 years in design with a companion article to focus on developments
in analysis. As a pair, these articles update the 2004 review. We have discussed
developments in the topics of the earlier review (e.g., clustering, matching, and
individually randomized group-treatment trials) and in new topics, including
constrained randomization and a range of randomized designs that are alternatives
to the standard parallel-arm GRT. These include the stepped-wedge GRT, the
pseudocluster randomized trial, and the network-randomized GRT, which, like the
parallel-arm GRT, require clustering to be accounted for in both their design and
analysis.
PMID- 28426298
TI - Mass Media Campaign to Reduce Consumption of Sugar-Sweetened Beverages in a Rural
Area of the United States.
AB - OBJECTIVES: To evaluate a mass media campaign to reduce the consumption of sugar
sweetened beverages (SSBs). METHODS: We disseminated messages emphasizing the
health risks of SSBs through television, digital channels, and local
organizations over 15 weeks in 2015-2016 in the Tri-Cities region of northeast
Tennessee, southwest Virginia, and southeast Kentucky. We evaluated the campaign
with pre- and post-telephone surveys of adults aged 18 to 45 years in the
intervention area and by examining changes in beverage sales in the intervention
and a matched comparison area in western Virginia. RESULTS: Fifty-four percent of
postcampaign respondents recalled seeing a campaign advertisement. After the
campaign, 53% of respondents believed SSBs were a cause of heart disease, and
respondents were more likely postcampaign to consider SSBs a "big cause of
diabetes" (75% vs 60%; P < .001). Compared with 12 months before, after the start
of the campaign, SSB sales decreased 3.4%, including a 4.1% decrease in soda
sales in the intervention area relative to the comparison area (P < .01).
CONCLUSIONS: This brief media campaign on SSBs was followed by intended changes
in beliefs and consumption. Public Health Implications. Additional media
campaigns on SSBs should be attempted and evaluated.
PMID- 28426299
TI - Effect of Legislation on Indoor Tanning Prevalence in Alabama.
AB - OBJECTIVES: To examine changes in indoor tanning prevalence among Alabama high
school students the year before and after its 2014 legal restrictions compared
with Florida, which had more lenient legislation. METHODS: We analyzed the
Alabama and Florida 2015 Youth Risk Behavior Survey (n = 14 389; population = 1
864 241) by gender, age, year (2013, 2015), state (Alabama, Florida), and year-by
state interactions. RESULTS: Prevalence of indoor tanning was higher among
Alabama youths, but the difference did not significantly change after the law was
passed in Alabama (between-state change differences ranged from a 3.3% increase
among 14-year-old Alabama girls to a 9.7% decrease among 14-year-old Alabama
boys). CONCLUSIONS: We found no significant changes in indoor tanning among
adolescents since the enactment of Alabama's tanning restrictions in 2014. More
oversight and monitoring are needed to ensure that indoor tanning facilities are
compliant with emerging laws.
PMID- 28426300
TI - Overview of Asian American Data Collection, Release, and Analysis: National
Health and Nutrition Examination Survey 2011-2018.
AB - Data System. The National Health and Nutrition Examination Survey (NHANES),
conducted by the National Center for Health Statistics, is a cross-sectional
survey on the health and nutritional status of US adults and children. Data
Collection/Processing. A complex, multistage probability design is used to select
a sample representative of the US civilian, noninstitutionalized population.
NHANES includes in-home interviews, physical examinations, and biospecimen
collection. About 5000 persons are examined annually. Since 2011, NHANES has been
oversampling Asian Americans in addition to traditionally oversampled groups,
including Hispanics and non-Hispanic Blacks. Data Analysis/Dissemination. Data
are publicly released online in 2-year cycles. Some data, because of disclosure
risk, are only available through the Research Data Center. Data users should read
documentation, examine sample sizes and response rates, and account for the
complex survey design. With publicly released data, analyses of Asians as a
single group is only possible; some Asian subgroup analyses may be conducted
through the Research Data Center. Public Health Implications. Oversampling Asians
in NHANES 2011-2018 allows national estimates to be computed on health
conditions, nutrition, and risk factors of public health importance on this
growing subpopulation of Asian Americans.
PMID- 28426301
TI - Small-Group Randomized Controlled Trial to Increase Condom Use and HIV Testing
Among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex With Men.
AB - OBJECTIVES: To evaluate the HOLA en Grupos intervention, a Spanish-language small
group behavioral HIV prevention intervention designed to increase condom use and
HIV testing among Hispanic/Latino gay, bisexual, and other men who have sex with
men. METHODS: In 2012 to 2015, we recruited and randomized 304 Hispanic/Latino
men who have sex with men, aged 18 to 55 years in North Carolina, to the 4
session HOLA en Grupos intervention or an attention-equivalent general health
education comparison intervention. Participants completed structured assessments
at baseline and 6-month follow-up. Follow-up retention was 100%. RESULTS: At
follow-up, relative to comparison participants, HOLA en Grupos participants
reported increased consistent condom use during the past 3 months (adjusted odds
ratio [AOR] = 4.1; 95% confidence interval [CI] = 2.2, 7.9; P < .001) and HIV
testing during the past 6 months (AOR = 13.8; 95% CI = 7.6, 25.3; P < .001). HOLA
en Grupos participants also reported increased knowledge of HIV (P < .001) and
sexually transmitted infections (P < .001); condom use skills (P < .001), self
efficacy (P < .001), expectancies (P < .001), and intentions (P < .001); sexual
communication skills (P < .01); and decreased fatalism (P < .001). CONCLUSIONS:
The HOLA en Grupos intervention is efficacious for reducing HIV risk behaviors
among Hispanic/Latino men who have sex with men.
PMID- 28426302
TI - Innovations in Population Health Surveillance: Using Electronic Health Records
for Chronic Disease Surveillance.
AB - With 87% of providers using electronic health records (EHRs) in the United
States, EHRs have the potential to contribute to population health surveillance
efforts. However, little is known about using EHR data outside syndromic
surveillance and quality improvement. We created an EHR-based population health
surveillance system called the New York City (NYC) Macroscope and assessed the
validity of diabetes, hyperlipidemia, hypertension, smoking, obesity, depression,
and influenza vaccination indicators. The NYC Macroscope uses aggregate data from
a network of outpatient practices. We compared 2013 NYC Macroscope prevalence
estimates with those from a population-based, in-person examination survey, the
2013-2014 NYC Health and Nutrition Examination Survey. NYC Macroscope diabetes,
hypertension, smoking, and obesity prevalence indicators performed well, but
depression and influenza vaccination estimates were substantially lower than were
survey estimates. Ongoing validation will be important to monitor changes in
validity over time as EHR networks mature and to assess new indicators. We
discuss NYC's experience and how this project fits into the national context.
Sharing lessons learned can help achieve the full potential of EHRs for
population health surveillance.
PMID- 28426303
TI - Measures of Local Segregation for Monitoring Health Inequities by Local Health
Departments.
AB - OBJECTIVES: To assess the use of local measures of segregation for monitoring
health inequities by local health departments. METHODS: We analyzed preterm birth
and premature mortality (death before the age of 65 years) rates for Boston,
Massachusetts, for 2010 to 2012, using the Index of Concentration at the Extremes
(ICE) and the poverty rate at both the census tract and neighborhood level.
RESULTS: For premature mortality at the census tract level, the rate ratios
comparing the worst-off and best-off terciles were 1.58 (95% confidence interval
[CI] = 1.36, 1.83) for the ICE for income, 1.66 (95% CI = 1.43, 1.93) for the ICE
for race/ethnicity, and 1.63 (95% CI = 1.40, 1.90) for the ICE combining income
and race/ethnicity, as compared with 1.47 (95% CI = 1.27, 1.71) for the poverty
measure. Results for the ICE and poverty measures were more similar for preterm
births than for premature mortality. CONCLUSIONS: The ICE, a measure of social
spatial polarization, may be useful for analyzing health inequities at the local
level. Public Health Implications. Local health departments in US cities can
meaningfully use the ICE to monitor health inequities associated with racialized
economic segregation.
PMID- 28426304
TI - State Preemption: A Significant and Quiet Threat to Public Health in the United
States.
AB - State and local governments traditionally protect the health and safety of their
populations more strenuously than does the federal government. Preemption, when a
higher level of government restricts or withdraws the authority of a lower level
of government to act on a particular issue, was historically used as a point of
negotiation in the legislative process. More recently, however, 3 new preemption
related issues have emerged that have direct implications for public health.
First, multiple industries are working on a 50-state strategy to enact state laws
preempting local regulation. Second, legislators supporting preemptive state
legislation often do not support adopting meaningful state health protections and
enact preemptive legislation to weaken protections or halt progress. Third,
states have begun adopting enhanced punishments for localities and individual
local officials for acting outside the confines of preemption. These actions have
direct implications for health and cover such topics as increased minimum wages,
paid family and sick leave, firearm safety, and nutrition policies. Stakeholders
across public health fields and disciplines should join together in advocacy,
action, research, and education to support and maintain local public health
infrastructures and protections.
PMID- 28426305
TI - US Public Opinion on Carrying Firearms in Public Places.
AB - OBJECTIVES: To estimate US public opinion, overall and by gun ownership status,
about the public places where legal gun owners should be allowed to carry
firearms. METHODS: We fielded an online survey among 3949 adults, including an
oversample of gun owners and veterans, in April 2015. We used cross-tabulations
with survey weights to generate nationally representative estimates. RESULTS:
Fewer than 1 in 3 US adults supported gun carrying in any of the specified
venues. Support for carrying in public was consistently higher among gun owners
than among non-gun owners. Overall, support for carrying in public was lowest for
schools (19%; 95% confidence interval [CI] = 16.7, 21.1), bars (18%; 95% CI =
15.9, 20.6), and sports stadiums (17%; 95% CI = 15.0, 19.5). CONCLUSIONS: Most
Americans, including most gun owners, support restricting public places legal gun
owners can carry firearms. These views contrast sharply with the current trend in
state legislatures of expanding where, how, and by whom guns can be carried in
public. Recent state laws and proposed federal legislation that would force
states to honor out-of-state concealed carry permits are out of step with
American public opinion.
PMID- 28426306
TI - Machine Learning for Social Services: A Study of Prenatal Case Management in
Illinois.
AB - OBJECTIVES: To evaluate the positive predictive value of machine learning
algorithms for early assessment of adverse birth risk among pregnant women as a
means of improving the allocation of social services. METHODS: We used
administrative data for 6457 women collected by the Illinois Department of Human
Services from July 2014 to May 2015 to develop a machine learning model for
adverse birth prediction and improve upon the existing paper-based risk
assessment. We compared different models and determined the strongest predictors
of adverse birth outcomes using positive predictive value as the metric for
selection. RESULTS: Machine learning algorithms performed similarly,
outperforming the current paper-based risk assessment by up to 36%; a refined
paper-based assessment outperformed the current assessment by up to 22%. We
estimate that these improvements will allow 100 to 170 additional high-risk
pregnant women screened for program eligibility each year to receive services
that would have otherwise been unobtainable. CONCLUSIONS: Our analysis exhibits
the potential for machine learning to move government agencies toward a more data
informed approach to evaluating risk and providing social services. Overall, such
efforts will improve the efficiency of allocating resource-intensive
interventions.
PMID- 28426307
TI - How California Prepared for Implementation of Physician-Assisted Death: A Primer.
AB - Physician-assisted death is now legal in California, and similar laws are being
considered in many other states. The California law includes safeguards, yet
health care providers will face practical and ethical issues while implementing
physician-assisted death that are not addressed by the law. To help providers and
health care facilities in California prepare to provide optimal care to patients
who inquire about physician-assisted death, we brought together experts from
California, Oregon, and Washington. We convened a conference of 112 stakeholders
in December 2015, and herein present their recommendations. Themes of
recommendations regarding implementation include (1) institutions should develop
and revise physician-assisted death policies; (2) legal physician-assisted death
will have implications for California's culturally and socioeconomically diverse
population, and for patients from vulnerable groups; (3) conscientious objection
and moral distress for health care providers must be considered; and (4)
palliative care is essential to the response to the law. The expert conference
participants' insights are a valuable guide, both for providers and health care
facilities in California planning or revising their response, and for other
jurisdictions where physician-assisted death laws are being considered or
implemented.
PMID- 28426308
TI - Humanitarian Needs Among Displaced and Female-Headed Households in Government
Controlled Areas of Syria.
AB - OBJECTIVES: To identify unmet needs and assistance priorities of displaced and
female-headed households in government-controlled areas of Syria. METHODS: In mid
2016, we undertook a survey of accessible areas, largely urban and government
controlled, to identify unmet needs and assistance priorities. We used a cluster
design with probability sampling to attain a final sample of 2405 households from
10 of 14 governorates; 31 of 65 (47.7%) districts were included that are home to
38.1% of people in need. RESULTS: Displaced and female-headed households were
more vulnerable than nondisplaced and male-headed households in numerous sectors.
Despite approximately half of surveyed households reporting receipt of
humanitarian assistance in the preceding month and apparently effective targeting
of assistance by vulnerability, unmet needs were nearly ubiquitous. CONCLUSIONS:
The humanitarian situation in inaccessible areas of Syria is likely to be
considerably worse; thus, findings presented here likely underestimate
humanitarian needs. Efforts to expand support to Syria's most vulnerable
households are desperately needed as are innovative targeting and modalities that
enable more efficient and effective assistance.
PMID- 28426309
TI - LGBTQ Health Surveillance: Data = Power.
PMID- 28426310
TI - A Public Health Approach to Hepatitis C in an Urban Setting.
AB - The clinical consequences of HCV infection are increasing because the population
with the highest prevalence of the infection, persons born between 1945 and 1965,
is aging. As a result, health care expenditures are expected to increase. Now
that a cure for HCV infection is the norm, a public health approach is necessary
to identify, link to care, and treat infected persons and prevent new infections.
We believe that the success of public health interventions, such as those for
tuberculosis, can be translated to HCV infection. New York City has many HCV
infected residents and has developed a public health approach to controlling the
HCV epidemic. It encompasses surveillance and monitoring, case finding, linkage
to care, care coordination, increasing clinical provider capacity for screening
and treatment, increasing public awareness, and primary prevention.
PMID- 28426311
TI - The Zika Virus Outbreak in Brazil: Knowledge Gaps and Challenges for Risk
Reduction.
AB - We analyzed uncertainties and complexities of the Zika virus outbreak in Brazil,
and we discuss risk reduction for future emergencies. We present the public
health situation in Brazil and concurrent determinants of the epidemic and the
knowledge gaps that persist despite building evidence from research, making
public health decisions difficult. Brazil has adopted active measures, but
producing desired outcomes may be uncertain because of partial or unavailable
information. Reducing population group vulnerabilities and acting on
environmental issues are medium- to long-term measures. Simultaneously dealing
with information gaps, uncontrolled disease spread, and vulnerabilities is a new
risk scenario and must be approached decisively to face emerging biothreats.
PMID- 28426312
TI - Safe Sex in the 1970s: Community Practitioners on the Eve of AIDS.
AB - In the 1970s, groups of gay and gay-allied health professionals began to
formulate guidelines for safer sexual activity, several years before HIV/AIDS.
Through such organizations as the National Coalition of Gay Sexually Transmitted
Disease Services, Bay Area Physicians for Human Rights, and the Sisters of
Perpetual Indulgence, these practitioners developed materials that would define
sexual health education for the next four decades, as well as such concepts as
"bodily fluids" and the "safe sex hanky." To do so, they used their dual
membership in the community and the health professions. Although the dichotomy
between the gay community and the medical establishment helped define the early
history of HIV/AIDS, the creative work of these socially "amphibious" activists
played an equally important part. Amid current debates over preexposure
prophylaxis against HIV and Zika virus transmission, lessons for sexual health
include the importance of messaging, the difficulty of behavioral change, and the
vitality of community-driven strategies to mitigate risk.
PMID- 28426313
TI - Restrictions of Hepatitis C Treatment for Substance-Using Medicaid Patients: Cost
Versus Ethics.
AB - Medicaid programs provide health insurance coverage for many patients with
hepatitis C, a public health problem for which effective but very expensive
treatments are now available. Facing constrained budgets, most states adopted
prior authorization criteria for sofosbuvir, the first of these agents. Using fee
for-service utilization data from 42 Medicaid programs in 2014, we found that
strict behavioral criteria-those that limited coverage on the basis of drug or
alcohol use and included specific abstinence or treatment requirements-were
associated with significantly less spending on sofosbuvir. Despite the potential
cost savings, such criteria raise troubling questions in terms of public health
as well as medical ethics, clinical evidence, and potentially federal law.
Decision-makers should reject these requirements in Medicaid coverage policy and
pursue national and state policy strategies to balance short-term budgetary
realities with long-term public health benefits.
PMID- 28426314
TI - The Influence of College Attendance on Risk for Marijuana Initiation in the
United States: 1977 to 2015.
AB - OBJECTIVES: To examine a potential increase in marijuana initiation among US
college students as compared with their age peers not in college before and after
2013, a watershed year for increasing tolerance of marijuana use in the United
States. METHODS: Data come from the Monitoring the Future study, which has
followed longitudinal panels drawn from annual nationally representative,
baseline samples of 12th-grade students starting with the class of 1976. We
studied panel members aged 19 to 22 years who had never used marijuana by 12th
grade between 1977 and 2015. RESULTS: College as a risk factor for marijuana
initiation has increased significantly since 2013. The increased probability of
past-year marijuana use for those enrolled versus not enrolled in college was 51%
in 2015, 41% in 2014, and 31% in 2013; it averaged 17% to 22% from 1977 to 2012
among youths who had never used marijuana by 12th grade. CONCLUSIONS: College has
grown as a risk factor for marijuana initiation since 2013. Public Health
Implications. College students are in position to usher in new increases in
population marijuana use unless colleges soon address the issue with new or
modified programs for marijuana prevention and intervention.
PMID- 28426315
TI - Medicaid Expansion and ACA Repeal: Evidence From Ohio.
AB - OBJECTIVES: To examine the health insurance coverage options for Medicaid
expansion enrollees if the Affordable Care Act (ACA) is repealed, using evidence
from Ohio, where more than half a million adults have enrolled in the state's
Medicaid program through the ACA expansion. METHODS: The Ohio Medicaid Assessment
Survey interviewed 42 000 households in 2015. We report data from a unique
battery of questions designed to identify insurance coverage immediately prior to
Medicaid enrollment. RESULTS: Ninety-five percent of new Medicaid enrollees in
Ohio did not have a private health insurance option immediately before
enrollment. These new enrollees are predominantly older, low-income Whites with a
high school education or less. Only 5% of new Medicaid enrollees were eligible
for an employer-sponsored insurance plan to which they could potentially return
in the case of repeal of the ACA. CONCLUSIONS: The vast majority of Medicaid
expansion enrollees would have no plausible pathway to obtaining private-sector
insurance if the ACA were repealed. Demographic similarities between the
expansion population and 2016 exit polls suggest that coverage losses would fall
disproportionately on members of the winning Republican coalition.
PMID- 28426316
TI - Framing Mechanisms Linking HIV-Related Stigma, Adherence to Treatment, and Health
Outcomes.
AB - We present a conceptual framework that highlights how unique dimensions of
individual-level HIV-related stigma (perceived community stigma, experienced
stigma, internalized stigma, and anticipated stigma) might differently affect the
health of those living with HIV. HIV-related stigma is recognized as a barrier to
both HIV prevention and engagement in HIV care, but little is known about the
mechanisms through which stigma leads to worse health behaviors or outcomes. Our
conceptual framework posits that, in the context of intersectional and structural
stigmas, individual-level dimensions of HIV-related stigma operate through
interpersonal factors, mental health, psychological resources, and biological
stress pathways. A conceptual framework that encompasses recent advances in
stigma science can inform future research and interventions aiming to address
stigma as a driver of HIV-related health.
PMID- 28426317
TI - Trends in Fighting and Violence Among Adolescents in the United States, 2002
2014.
AB - OBJECTIVES: To examine trends in and correlates of fighting and violence among
youths from the 3 largest racial/ethnic groups in the United States. METHODS: We
derived race/ethnicity-specific prevalence estimates for fighting, group
fighting, and attacks with intent to harm from the National Survey on Drug Use
and Health, a population-based study of youths aged 12 to 17 years. RESULTS: The
prevalence of youth fighting and violence decreased significantly in all
racial/ethnic groups over the study period (2002-2014), dropping from a high of
33.6% in 2003 to a low of 23.7% in 2014, reflecting a 29% decrease in the
relative proportion of young people involved in these behaviors. However, there
was also a clear severity gradient in which year-by-year point estimates for
fighting and violence were consistently highest among non-Hispanic African
American youths, followed by Hispanic and then non-Hispanic White youths.
CONCLUSIONS: Although fighting and violence are on the decline among young people
in general and across racial/ethnic subgroups, there is a stable pattern of
disparities in youth involvement in these behaviors.
PMID- 28426318
TI - US State Statutes Banning Powdered Alcohol: Exceptions and Penalties.
AB - To examine state statutes banning powdered alcohol, we identified relevant
statutes in all 50 states and the District of Columbia through a search (initial
search March 2016; follow-up search November 2016) using the legal research
database LexisNexis. To identify the laws, we used the following search terms:
"concentrated alcohol," "crystalline alcohol," "granulated alcohol," "palcohol,"
and "powdered alcohol." As of November 2016, 31 states had statutory bans on
powdered alcohol. Statutes in 22 states outline penalties for violating the
state's ban on powdered alcohol. Five states include suspension and revocation of
alcohol beverage licenses and permits among the penalties. Thirteen states
provide exceptions to their ban on powdered alcohol for bona fide scientific
research. Twelve states have exceptions for powdered alcohol designed for
commercial use or not intended for human consumption. With concerns expressed
that powdered alcohol may lead to greater alcohol consumption, particularly among
minors, the majority of state legislatures have demonstrated their willingness to
restrict access to novel alcohol products to protect the public's health.
However, the effectiveness of these laws should be evaluated if the product does
become available.
PMID- 28426319
TI - The Monetary Cost of Sexual Assault to Privately Insured US Women in 2013.
AB - OBJECTIVES: To determine whether privately insured female rape victims were
billed for charges associated with a specific rape in the United States. METHODS:
We examined 2013 de-identified patient data from Truven Analytics Health
MarketScan database for an assault that occurred by using International
Classification of Diseases, Ninth Revision, code E960.1. RESULTS: Analysis of
insurance providers' payment patterns for 1355 incident events to female victims
aged between 16 and 61 years revealed that victims remit, on average, 14% or $948
of the rape cost, whereas insurance providers pay 86% or $5789 of the total cost.
CONCLUSIONS: Hospital billing procedures for privately insured victims of rape
across the United States are not separate from billing procedures for privately
insured nonrape patients. This standardized procedure leads hospitals to bill
victims directly for services not paid under the victims' insurance policy.
Public Health Implications. The Violence Against Women Act (passed in 1994,
reauthorized in 2000, 2005, and 2013) must be amended to mandate that all costs
incurred because of rape are not passed on to the victim.
PMID- 28426321
TI - Hansae Vietnam's garment factory: Latest example of how corporate social
responsibility has failed to protect workers.
PMID- 28426320
TI - Transient exposure to androgens induces a remarkable self-sustained quiescent
state in dispersed prostate cancer cells.
AB - Cellular quiescence is a reversible cell growth arrest that is often assumed to
require a persistence of non-permissive external growth conditions for its
maintenance. In this work, we showed that androgen could induce a quiescent state
that is self-sustained in a cell-autonomous manner through a "hit and run"
mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon
required the set-up of a sustained redox imbalance and TGFbeta/BMP signaling that
were dependent on culturing cells at low density. At medium cell density,
androgens failed to induce such a self-sustained quiescent state, which
correlated with a lesser induction of cell redox imbalance and oxidative stress
markers like CDKN1A. These effects of androgens could be mimicked by transient
overexpression of CDKN1A that triggered its own expression and a sustained SMAD
phosphorylation in cells cultured at low cell density. Overall, our data suggest
that self-sustained but fully reversible quiescent states might constitute a
general response of dispersed cancer cells to stress conditions.
PMID- 28426322
TI - Formative Research to Design a Promotional Campaign to Increase Drinking Water
among Central American Latino Youth in an Urban Area.
AB - Latinos consume more sugary drinks and less water than other demographic groups.
Our objective was to understand beverage choice motivations and test promotional
concepts that can encourage Central American Latino urban youth to drink more
water. Two rounds of focus group discussions were conducted (n = 10 focus groups,
61 participants, 6-18 years old). Data were transcribed verbatim and analyzed
using inductive and deductive coding approaches. Youth motivations for drinking
water were shaped by level of thirst, weather, energy, and perceptions of health
benefits. Youth were discouraged from drinking water due to its taste and
perceptions of the safety and cleanliness of tap water. Youth beverage preference
depended on what their friends were drinking. Availability of water versus other
beverages at home and other settings influenced their choice. Promotional
materials that included mixed language, informative messages about the benefits
of drinking water, and celebrities or athletes who were active, energized, and
drinking water were preferred. A promotional campaign to increase water
consumption among these Latino youth should include bicultural messages to
underscore the power of water to quench true thirst, highlight the health
benefits of drinking water, and address the safety of tap water.
PMID- 28426323
TI - Letters From Our Readers.
PMID- 28426324
TI - Letters From Our Readers.
PMID- 28426325
TI - Letters From Our Readers.
PMID- 28426328
TI - Fast Food or Slow Food Orthodontics? Part 2.
PMID- 28426327
TI - Letters From Our Readers.
PMID- 28426329
TI - Mathematical modelling of CRISPR-Cas system effects on biofilm formation.
AB - Clustered regularly interspaced short palindromic repeats (CRISPR), linked with
CRISPR associated (Cas) genes, can confer adaptive immunity to bacteria, against
bacteriophage infections. Thus from a therapeutic standpoint, CRISPR immunity
increases biofilm resistance to phage therapy. Recently, however, CRISPR-Cas
genes have been implicated in reducing biofilm formation in lysogenized cells.
Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions,
particularly in a biofilm. In this contribution, we develop and analyse a series
of dynamical systems to elucidate and disentangle these interactions. Two
competition models are used to study the effects of lysogens (first model) and
CRISPR-immune bacteria (second model) in the biofilm. In the third model, the
effect of delivering lysogens to a CRISPR-immune biofilm is investigated. Using
standard analyses of equilibria, stability and bifurcations, our models predict
that lysogens may be able to displace CRISPR-immune bacteria in a biofilm, and
thus suggest strategies to eliminate phage-resistant biofilms.
PMID- 28426330
TI - The transformation of the meaning of death in complicated grief group therapy for
survivors of suicide: A treatment process analysis using the meaning of loss
codebook.
AB - We examined the therapeutic process of grief change in survivors of suicide
participating in complicated grief group therapy (CGGT) using the meaning of loss
codebook (MLC). Complicated grief group therapy is a multimodal group
psychotherapy designed to restore normal grieving in persons with complicated
grief. Using video data, we evaluated transition points in psychotherapy
associated with meaning reconstruction: retelling the narrative of the death,
having an imaginal conversation with the deceased, and memory integration. The
MLC codes captured most of the voiced statements of participants, provided a
valuable lens for articulating the therapeutic process, and affirmed that CGGT
facilitated effective grief.
PMID- 28426331
TI - Effect of deletion of 2,3-butanediol dehydrogenase gene (bdhA) on acetoin
production of Bacillus subtilis.
AB - The present work aims to block 2,3-butanediol synthesis in acetoin fermentation
of Bacillus subtilis. First, we constructed a recombinant strain BS168D by
deleting the 2,3-butanediol dehydrogenase gene bdhA of the B. subtilis168, and
there was almost no 2,3-butanediol production in 20 g/L of glucose media. The
acetoin yield of BS168D reached 6.61 g/L, which was about 1.5 times higher than
that of the control B. subtilis168 (4.47 g/L). Then, when the glucose
concentration was increased to 100 g/L, the acetoin yield reached 24.6 g/L, but
2.4 g/L of 2,3-butanediol was detected at the end of fermentation. The analysis
of 2,3-butanediol chiral structure indicated that the main 2,3-butanediol
production of BS168D was meso-2,3-butanediol, and the bdhA gene was only
responsible for (2R,3R)-2,3-butanediol synthesis. Therefore, we speculated that
there may exit another pathway relating to the meso-2,3-butanediol synthesis in
the B. subtilis. In addition, the results of low oxygen condition fermentation
showed that deletion of bdhA gene successfully blocked the reversible
transformation between acetoin and 2,3-butanediol and eliminated the effect of
dissolved oxygen on the transformation.
PMID- 28426333
TI - Existence and uniqueness for a coupled PDE model for motor-induced microtubule
organization.
AB - Microtubules (MTs) are protein filaments that provide structure to the
cytoskeleton of cells and a platform for the movement of intracellular
substances. The spatial organization of MTs is crucial for a cell's form and
function. MTs interact with a class of proteins called motor proteins that can
transport and position individual filaments, thus contributing to overall
organization. In this paper, we study the mathematical properties of a coupled
partial differential equation (PDE) model, introduced by White et al. in 2015,
that describes the motor-induced organization of MTs. The model consists of a
nonlinear coupling of a hyperbolic PDE for bound motor proteins, a parabolic PDE
for unbound motor proteins, and a transport equation for MT dynamics. We locally
smooth the motor drift velocity in the equation for bound motor proteins. The
mollification is not only critical for the analysis of the model, but also adds
biological realism. We then use a Banach Fixed Point argument to show local
existence and uniqueness of mild solutions. We highlight the applicability of the
model by showing numerical simulations that are consistent with in vitro
experiments.
PMID- 28426332
TI - Buprenorphine Treatment and Patient Use of Health Services after the Affordable
Care Act in an Integrated Health Care System.
AB - The Affordable Care Act (ACA) was expected to benefit patients with substance use
disorders, including opioid use disorders (OUDs). This study examined
buprenorphine use and health services utilization by patients with OUDs pre- and
post-ACA in a large health care system. Using electronic health record data, we
examined demographic and clinical characteristics (substance use, psychiatric and
medical conditions) of two patient cohorts using buprenorphine: those newly
enrolled in 2012 ("pre-ACA," N = 204) and in 2014 ("post-ACA," N = 258). Logistic
and negative binomial regressions were used to model persistent buprenorphine
use, and to examine whether persistent use was related to health services
utilization. Buprenorphine patients were largely similar pre- and post-ACA,
although more post-ACA patients had a marijuana use disorder (p < .01). Post-ACA
patients were more likely to have high-deductible benefit plans (p < .01). Use of
psychiatry services was lower post-ACA (IRR: 0.56, p < .01), and high-deductible
plans were also related to lower use of psychiatry services (IRR: 0.30, p < .01).
The relationship between marijuana use disorder and prescription opioid use is
complex, and deserves further study, particularly with increasingly widespread
marijuana legalization. Access to psychiatry services may be more challenging for
buprenorphine patients post-ACA, especially for patients with deductible plans.
PMID- 28426334
TI - Myopigenic Activity Change and Its Risk Factors in Urban Students in Beijing:
Three-Year Report of Beijing Myopia Progression Study.
AB - PURPOSE: To investigate the myopigenic activity change and its risk factors in
urban students in Beijing. METHODS: A total of 241 primary or secondary students
aged 6-17 years from the Beijing Myopia Progression Study (BMPS) were re-examined
3 years after their baseline enrollment. A detailed questionnaire was
administered to assess myopigenic activities at both baseline and at the 3-year
follow-up. Altogether, 217 students (90.0%) with completed data were included in
the analysis. RESULTS: Compared to baseline, primary students (n = 123) had
significant increases in outdoor sports time (mean +/- standard deviation: 3.5 +/
4.3 vs. 2.4 +/- 3.0 hours/week, p = 0.02), near work time (32.1 +/- 13.4 vs.
24.8 +/- 9.2 hours/week, p < 0.001), diopter hours (128.8 +/- 53.3 vs. 97.5 +/-
35.9 diopter hours/week, p < 0.001), and indoor time (53.8 +/- 22.8 vs. 41.4 +/-
16.9 hours/week, p < 0.001) at the 3-year follow-up. At both baseline and follow
up, females spent less time than males on outdoor sports (baseline: 2.4 +/- 2.8
vs. 4.0 +/- 5.2 hours/week, p = 0.006; follow-up: 2.3 +/- 3.1 vs. 5.1 +/- 5.0
hours/week, p < 0.001), and total outdoors (baseline: 11.9 +/- 7.9 vs. 14.4 +/-
9.5 hours/week, p = 0.03; follow-up: 10.5 +/- 8.2 vs. 13.9 +/- 9.6 hours/week, p
= 0.005). In the multivariate regression analysis after adjustment by student's
gender, younger students had more increase in both near work time (slope = -0.99
hours/week for age, p = 0.009) and indoor time (slope = -2.04 hours/week for age,
p = 0.001). CONCLUSIONS: During the 3-year follow-up, primary students had more
myopigenic activities. Female students had more myopigenic activities than males
at both baseline and follow-up. Children's age was a significant risk factor for
this myopigenic activity change.
PMID- 28426335
TI - Chaplaincy Encounters Following a Suicide Attempt.
AB - This descriptive study examines the provision of chaplaincy services to veterans
who sought health care at a Department of Veterans Affairs (VA) Medical Center
following a suicide attempt. A system-wide VA database of suicidal behavior was
used to identify a cohort of n = 22,701 veterans who survived a suicide attempt.
Next, an electronic review of VA clinical records found that n = 7,447 (32.8%)
received chaplaincy services in the 30 days following their attempt. Of this
group, the overwhelming majority of first chaplaincy encounters took place in in
patient settings: n = 6890 (92.5%). First chaplaincy encounters most often
occurred 1-7 days following the attempt: n = 5,033 (67.6%). Most chaplaincy
service users had only one chaplaincy encounter: n = 3,514 (47.2%). The findings
suggest that, at VA Medical Centers, a relatively sizeable percentage of suicide
attempt survivors have contact with chaplaincy services. Additional research is
needed to ascertain if chaplaincy services yield any therapeutic benefit for this
group.
PMID- 28426336
TI - Effect of Laser Energy and Tip Insertion Depth on the Pressure Generated Outside
the Apical Foramen During Er:YAG Laser-Activated Root Canal Irrigation.
AB - OBJECTIVE: The risk of extrusion of irritative irrigants into the extraradicular
tissue should be minimized during root canal irrigation. This study aimed to
examine the pressure generated outside the apex during Er:YAG laser-activated
irrigation (LAI) in comparison with passive ultrasonic irrigation (PUI) and
conventional syringe irrigation (SI). BACKGROUND DATA: LAI is reported to be
efficient for root canal debridement, whereas the apical pressure generated
during LAI has not been investigated in detail. METHODS: Plastic root canal
models (apical diameter = 0.40 mm, taper = 6%, and length = 20 mm) were irrigated
with water using either LAI with an Er:YAG laser (Erwin AdvEr; 30, 50, or 70 mJ,
10 pps), PUI, or SI. The tip insertion depth was set at 2, 5, or 10 mm from the
apex. The pressure generated outside the apical foramen was measured with a
pressure sensor connected to the apex of the model. RESULTS: When the tip was
positioned at 2 mm and the power setting was changed, the mean maximum pressure
values were LAI (30 mJ) = PUI < LAI (70 mJ) < SI (p < 0.05). When LAI was
performed at 70 mJ and the tip was positioned at 5 or 10 mm, the pressure values
were PUI < LAI = SI (p < 0.05). CONCLUSIONS: LAI generated similar or lower
pressure outside the apical foramen compared with SI, irrespective of the laser
energy and tip insertion depth examined. However, LAI generated higher pressure
compared with PUI.
PMID- 28426337
TI - The Goal of Better Understanding the Applications of Laser Therapy in Periodontal
Disease Management in the 21st Century.
PMID- 28426338
TI - Causes of death in long-term lung cancer survivors: a SEER database analysis.
AB - BACKGROUND: Long-term (>5 years) lung cancer survivors represent a small but
distinct subgroup of lung cancer patients and information about the causes of
death of this subgroup is scarce. METHODS: The Surveillance, Epidemiology and End
Results (SEER) database (1988-2008) was utilized to determine the causes of death
of long-term survivors of lung cancer. Survival analysis was conducted using
Kaplan-Meier analysis and multivariate analysis was conducted using a Cox
proportional hazard model. Clinicopathological characteristics and survival
outcomes were assessed for the whole cohort. RESULTS: A total of 78,701 lung
cancer patients with >5 years survival were identified. This cohort included
54,488 patients surviving 5-10 years and 24,213 patients surviving >10 years.
Among patients surviving 5-10 years, 21.8% were dead because of primary lung
cancer, 10.2% were dead because of other cancers, 6.8% were dead because of
cardiac disease and 5.3% were dead because of non-malignant pulmonary disease.
Among patients surviving >10 years, 12% were dead because of primary lung cancer,
6% were dead because of other cancers, 6.9% were dead because of cardiac disease
and 5.6% were dead because of non-malignant pulmonary disease. On multivariate
analysis, factors associated with longer cardiac-disease-specific survival in
multivariate analysis include younger age at diagnosis (p < .0001), white race
(vs. African American race) (p = .005), female gender (p < .0001), right-sided
disease (p = .003), adenocarcinoma (vs. large cell or small cell carcinoma),
histology and receiving local treatment by surgery rather than radiotherapy (p <
.0001). CONCLUSION: The probability of death from primary lung cancer is still
significant among other causes of death even 20 years after diagnosis of lung
cancer. Moreover, cardiac as well as non-malignant pulmonary causes contribute a
considerable proportion of deaths in long-term lung cancer survivors.
PMID- 28426339
TI - Fasting levels of insulin and amylin after acute pancreatitis are associated with
pro-inflammatory cytokines.
AB - BACKGROUND: The prevalence of metabolic diseases continues to rise worldwide,
with a growing recognition of metabolic dysregulation after acute inflammatory
diseases such as acute pancreatitis (AP). Adipokines and cytokines play an
important role in metabolism and the course of AP, but there is a paucity of
research investigating their relationship with pancreatic hormones after AP. This
study aimed to explore associations between pancreatic hormones and adipokines as
well as cytokines to provide insights into the pathophysiology of altered
pancreatic hormone secretion following AP [corrected]. METHODS: A total of 83
patients previously diagnosed with AP and no prior diabetes or pre-diabetes were
recruited into this cross-sectional follow up study. Fasting venous blood samples
were collected to analyse a panel of pancreatic hormones and derivatives (amylin,
C-peptide, glucagon, insulin, pancreatic polypeptide, somatostatin), adipokines
(adiponectin, leptin, retinol binding protein-4, and resistin), and cytokines
(interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumour
necrosis factor-alpha (TNF-alpha)). Linear regression analyses were used, and
potential confounders were adjusted for in multivariate analyses. RESULTS:
Insulin was significantly associated with IL-6 in both unadjusted and adjusted
models (p = .029 and p = .040, respectively). Amylin was significantly associated
with MCP-1 in the unadjusted model (p = .046), and TNF-alpha in unadjusted and
adjusted models (p = .025 and p = .027, respectively). CONCLUSIONS: Insulin and
amylin have a strong positive association with pro-inflammatory cytokines in
patients following an episode of AP. These associations have possible relevance
in the development of diabetes associated with diseases of the exocrine pancreas,
providing the opportunity to develop novel treatment paradigms.
PMID- 28426340
TI - A Novel Recombinant Canine Adenovirus Type 1 Detected from Acute Lethal Cases of
Infectious Canine Hepatitis.
AB - In this study, canine adenoviruses (CAdVs) from two acute fatal cases of
infectious canine hepatitis (ICH) were analyzed using molecular detection and
sequencing of the pVIII, E3, and fiber protein genes. Pathological findings in
affected dogs were typical for CAdV-1 associated disease, characterized by severe
centrilobular to panlobular necrohemorrhagic hepatitis and the development of
disseminated intravascular coagulation in the terminal stages of disease.
Comparison of partial genome sequences revealed that although these newly
detected viruses mainly had CAdV-1 genome characteristics, their pVIII gene was
more similar to that of CAdV-2. This likely suggests that a recombination has
occurred between CAdV-1 and CAdV-2, which possibly explains the cause of vaccine
failure or increased virulence of the virus in the observed ICH cases.
PMID- 28426341
TI - Mydriatics release from solid and semi-solid ophthalmic formulations using
different in vitro methods.
AB - The aim of the present paper was the development of semi-solid (hydrogels) and
solid (film) ophthalmic formulations for the controlled release of two
mydriatics: phenylephrine and tropicamide. The formulations - based on
polyvinylalcohol and hyaluronic acid - were characterized, and release studies
were performed with three different in vitro set-ups, i.e. Franz-type diffusion
cell, vial method and inclined plane; for comparison, a solution and a commercial
insert, both clinically used to induce mydriasis, were evaluated. Both gels and
film allowed for a controlled release of drugs, appearing a useful alternative
for mydriatics administration. However, the release kinetic was significantly
influenced by the method used, highlighting the need for optimization and
standardization of in vitro models for the evaluation of drug release from
ophthalmic dosage forms.
PMID- 28426342
TI - Perceived ideal body size of Ghanaian women: "Not too skinny, but not too fat".
AB - Body size issues are gaining public health attention because of the fast rising
epidemic of overweight and obesity across the globe. This study explored Ghanaian
women's subjective perceptions regarding ideal body size for women. A purposive
sampling strategy was employed in recruiting 36 women across the body weight
spectrum from Tamale (n = 17) and Accra (n = 19) in Ghana. Qualitative data were
obtained from in-depth interviews using a semi-structured interview guide. Data
from the interviews were analyzed deductively. The mean body mass index of
participants was 33.5 +/- 10 kg/m2: sixteen of the participants were obese, eight
were overweight, eleven were normal weight, and one was underweight. The
participants almost unanimously had a preference for an ideal body size slightly
above the normal, but not necessarily obese. Typically described as "not too
skinny, but not too fat," this preferred ideal reflected a fuller, curvier, and
shapelier body, as opposed to the Western ideal of thinner body type. Women often
felt pressured by peers and family members to have a slightly heavier body size.
Health education efforts are needed to focus on messages that seek to challenge
existing body size perceptions that may inhibit women's willingness to maintain a
healthy body weight.
PMID- 28426343
TI - De Novo Mutation of KAT6B Gene Causing Atypical Say-Barber-Biesecker-Young
Simpson Syndrome or Genitopatellar Syndrome.
AB - Mutations in KAT6B gene are responsible for Say-Barber-Biesecker-Young-Simpson
syndrome (SBBYSS) and genitopatellar syndrome (GPS), with most mutations
occurring in exon 18. A 4-year-old Chinese boy presented with short stature but
no other clinical features of SBBYSS or GPS had a de novo novel nonsense
pathogenic mutation in exon 14 of the KAT6B gene at position c.2636T>A
(p.Leu879X). The correlation analysis of genotype-phenotype indicated distinctive
clinical features (short stature, growth hormone deficiency, and delayed bone
age) compared with the classical mutations of KAT6B gene. To the best of our
knowledge, this is the first report of KAT6B gene mutation in any Chinese
individual. This work expands the mutant phenotypic spectrum of the KAT6B gene.
PMID- 28426344
TI - Primary Pediatric Breast Lesions: Comparing the Prevalence of Malignancies in the
Middle East with North America; Review of 1031 Cases.
AB - Benign breast masses are uncommon but are becoming more recognized among the
pediatric population. Malignant breast lesions are very rare. The aim of our
study was to review and compare the demographics, clinical presentation,
treatment, and outcomes of breast lesions, including primary malignancies, and to
discuss theories that may explain why there is an increased rate of breast
cancers diagnosed at a younger age in the Egyptian population. A total of 1031
cases were reviewed. Comparisons were made between the Egyptian (n = 846) and US
(n = 185) cohorts. There were 30 (3.5%) malignant tumors in the Egyptian group
with 17 (2%) deaths versus 3 (1.6%) malignant tumors in the US group with 2 (1%)
deaths (p = 0.247). The relative risk of breast cancer in the Egyptian group was
2.16 (95% confidence interval (CI): 0.67-7.01) compared with the US group. The
trend for increased risk of breast cancer in Egypt may be due to delayed
diagnosis because of decreased awareness.
PMID- 28426345
TI - Economic evaluation of ezetimibe treatment in combination with statin therapy in
the United States.
AB - AIMS: This study assessed the cost-effectiveness of ezetimibe with statin therapy
vs statin monotherapy from a US payer perspective, assuming the impending patent
expiration of ezetimibe. METHODS: A Markov-like economic model consisting of 28
distinct health states was used. Model population data were obtained from US
linked claims and electronic medical records, with inclusion criteria based on
diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses,
and cost-effectiveness analyses. The base-case scenario was used to evaluate the
cost-effectiveness of adding ezetimibe 10 mg to statin in patients aged 35-74
years with a history of coronary heart disease (CHD) and/or stroke, and with low
density lipoprotein cholesterol (LDL-C) levels >=70 mg/dL over a lifetime
horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into
account the impending patent expiration in the second quarter of 2017. Sub-group
analyses included patients with LDL-C levels >=100 mg/dL and patients with
diabetes with LDL-C levels >=70 mg/dL. RESULTS: The lifetime discounted
incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was
$9,149 per quality-adjusted life year (QALY) for the base-case scenario. For
patients with LDL-C levels >=100 mg/dL, the ICER was $839/QALY; for those with
diabetes and LDL-C levels >=70 mg/dL, it was $560/QALY. One-way sensitivity
analyses showed that the model was sensitive to changes in cost of ezetimibe,
rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base
case and sub-group analyses. LIMITATIONS: Indirect costs or treatment
discontinuation estimation were not included. CONCLUSIONS: Compared with statin
monotherapy, ezetimibe with statin therapy was cost-effective for secondary
prevention of CHD and stroke and for primary prevention of these conditions in
patients whose LDL-C levels are >=100 mg/dL and in patients with diabetes, taking
into account a 90% cost reduction for ezetimibe.
PMID- 28426346
TI - Correlates of Current Smoking Among Adults Served by the Public Mental Health
System.
AB - OBJECTIVE: As part of a study of health status among 457 adults with
diagnostically heterogeneous serious mental illnesses served by the public mental
health system in four U.S. states, we assessed predictors of current cigarette
smoking. METHODS: We examined bivariate relationships between smoking status and
risks for drug and alcohol use disorders, residential setting, parental status,
and employment. Finally, we used multivariable logistic regression to predict
current smoking, controlling for significant confounds. RESULTS: Of the total
sample, 44% of participants reported that they currently smoked and most (62%)
were moderately to severely nicotine-dependent. Those at high risk for drug use
disorders were more than three times as likely and those at high risk for alcohol
use disorders were more than twice as likely to smoke, compared to their
counterparts with little or no drug or alcohol use disorder risk. Controlling for
all other model variables including drug and alcohol disorder risk, current
smokers were less likely to be parents and more likely to reside in supervised
settings than nonsmokers. Younger people and those without a college degree were
more likely to smoke, controlling for all other model variables. CONCLUSIONS:
Given the high degree of comorbidity of smoking, alcohol disorders, and drug use
disorders, the authors highlight the need for integrated interventions that
address these issues simultaneously.
PMID- 28426347
TI - Mismatch repair regulates Cdt1 after UV damage.
PMID- 28426348
TI - Traumatic brain injury and lifetime suicidality: Applying the interpersonal
psychological theory perspective.
AB - The present article investigates the traumatic brain injury (TBI)-suicide link,
assessing whether (a) TBI accounts for variance in suicide risk, and (b) the
interpersonal-psychological theory of suicide can be applied to TBI status.
Matched case-control procedures applied to archival college student health data
identified TBI and non-TBI subsamples (84 total). Individuals with a TBI
possessed higher suicide risk than those without. Even accounting for the
relative influence of strong suicide risk factors (i.e., depression, perceived
burdensomeness, thwarted belongingness, and acquired capability), TBI was
robustly associated with suicide risk. TBI history would be valuable to ascertain
in assessing suicide risk.
PMID- 28426349
TI - RNA-binding protein RBM14 regulates dissociation and association of non
homologous end joining proteins.
AB - Defects in the DNA damage response (DDR) are associated with multiple diseases,
including cancers and neurodegenerative disorders. Emerging evidence indicates
involvement of RNA-binding proteins (RBPs) in DDR. However, functions of RBPs in
the DDR pathway remain elusive. We have shown previously that the RNA-binding
protein RBM14 is required for non-homologous end joining (NHEJ). Here we show
that RBM14 is required for efficient recruitment of XRCC4 and XLF to chromatin
and the release of KU proteins from chromatin upon DNA damage. Failure of this
process leads to accumulation of double-strand breaks (DSBs) in cells. Thus RBM14
plays crucial role in regulation of NHEJ upon DNA damage.
PMID- 28426350
TI - Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients
With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus
Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.
AB - Purpose The standard treatment of patients with diffuse large B-cell lymphoma
(DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin,
vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent,
has shown activity in DLBCL. This randomized phase III trial compared
lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL
who achieved a complete response (CR) or partial response (PR) to R-CHOP
induction. Methods Patients with previously untreated DLBCL or other aggressive B
cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of
R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo
for 21 days of every 28-day cycle for 24 months. The primary end point was
progression-free survival (PFS). Results A total of 650 patients were randomly
assigned. At the time of the primary analysis (December 2015), with a median
follow-up of 39 months from random assignment, median PFS was not reached for
lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95%
CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups
(eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3,
age younger than 70 v >= 70 years), response (PR v CR) after R-CHOP, and positron
emission tomography status at assignment (negative v positive). With longer
median follow-up of 52 months (October 2016), overall survival was similar
between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common
grade 3 or 4 adverse events associated with lenalidomide versus placebo
maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%),
respectively. Conclusion Lenalidomide maintenance for 24 months after obtaining a
CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.
PMID- 28426351
TI - The absence of crossovers on chromosome 4 in Drosophila melanogaster:
Imperfection or interesting exception?
AB - Drosophila melanogaster chromosome 4 is an anomaly because of its small size,
chromatin structure, and most notably its lack of crossing over during meiosis.
Earlier ideas about the absence of crossovers on 4 hypothesize that these unique
characteristics function to prevent crossovers. Here, we explore hypotheses about
the absence of crossovers on 4, how these have been addressed, and new insights
into the mechanism behind this suppression. We review recently published results
that indicate that global crossover patterning, in particular the centromere
effect, make a major contribution to the prevention of crossovers on 4.
PMID- 28426352
TI - The "risky" reading strategy revisited: New simulations using E-Z Reader.
AB - Eye-movement studies have demonstrated that, relative to college-aged readers,
older readers of alphabetic languages like English and German tend to read more
slowly, making more frequent and longer fixations and longer saccades, and
skipping more words, but also making more frequent regressions. These findings
have led to suggestions that older readers either adopt a "risky" strategy of
using context to "guess" words as a way of compensating for slower rates of
lexical processing, or have a smaller and more asymmetrical perceptual span.
Unfortunately, neither of these hypotheses seemingly explains more recent
observations that older readers of Chinese seem to adopt a more "conservative"
strategy, making shorter saccades and skipping less often. In this paper, we use
the E-Z Reader model of eye-movement control to examine several possible accounts
of the differences between college-aged and older readers of both alphabetic and
non-alphabetic languages. These simulations re-confirm that the "risky" strategy
may be sufficient to explain age-related differences in reader's eye movements,
with older readers of English versus Chinese being, respectively, more versus
less inclined to guess upcoming words. The implications of these results for
aging, reading, and models of eye-movement control are discussed.
PMID- 28426353
TI - Potential Risks of Ecological Momentary Assessment Among Persons Who Inject
Drugs.
AB - BACKGROUND: Ecological momentary assessment (EMA)-which often involves brief
surveys delivered via mobile technology-has transformed our understanding of the
individual and contextual micro-processes associated with legal and illicit drug
use. However, little empirical research has focused on participant's perspective
on the probability and magnitude of potential risks in EMA studies. OBJECTIVES:
To garner participant perspectives on potential risks common to EMA studies of
illicit drug use. METHODS: We interviewed 38 persons who inject drugs living in
San Diego (CA) and Philadelphia (PA), United States. They completed simulations
of an EMA tool and then underwent a semi-structured interview that systematically
explored domains of risk considered within the proposed revisions to the Federal
Policy for the Protection of Human Subjects or the "Common Rule." Interviews were
transcribed verbatim and coded systematically to explore psychological, physical,
social, legal, and informational risks from participation. RESULTS: Participants
perceived most risks to be minimal. Some indicated that repetitive questioning
about mood or drug use could cause psychological (i.e., anxiety) or behavioral
risks (i.e., drug use relapse). Ironically, the questions that were viewed as
risky were considered motivational to engage in healthy behaviors. The most cited
risks were legal and social risks stemming from participant concerns about data
collection and security. IMPORTANCE: Improving our understanding of these issues
is an essential first step to protect human participants in future EMA research.
We provide a brief set of recommendations that can aid in the design and ethics
review of the future EMA protocol with substance using populations.
PMID- 28426354
TI - "It Goes on Everywhere": Injection Drug Use in Canadian Federal Prisons.
AB - BACKGROUND: International and Canadian research on in-prison injection drug use
has documented the frequency of its occurrence as well as some of the resulting
consequences such as increased prevalence of HIV and hepatitis C virus. Access to
prison-based harm reduction programing is thus important. OBJECTIVES: The aim of
this study was to learn from former prisoner experiences and insights on in
prison injection drug use in order to advance and improve access to harm
reduction options, in particular prison-based needle and syringe programs
(PNSPs). METHODS: The qualitative and community-based study was conducted in
2014/2015 and included former prisoners from Ontario, Canada (N = 30) who had
recent experience of incarceration in a federal prison and knowledge of injection
drug use. Data analysis followed the deductive approach, drawing on the expertise
of the academic and community-based research team members. RESULTS: Interview and
focus group participants disclosed that drugs are readily available in Canadian
federal prisons and that equipment used to inject is accessed in a variety of
ways, sometimes gained through illicit means and sometimes made by prisoners
themselves. Equipment sharing is a frequent occurrence, and disposal of such
supplies is rare. Conclusions/Importance: While not yet available in Canada,
PNSPs have led to positive outcomes in international contexts, including
reductions in needle sharing and transmission of HIV and hepatitis C. Support for
PNSPs among numerous Canadian organizations and associations, along with a recent
change in government, could suggest a renewed opportunity for PNSP
implementation.
PMID- 28426355
TI - Income Levels and Response to Contingency Management for Smoking Cessation.
AB - BACKGROUND: Contingency management (CM) has demonstrated its efficacy in treating
many drug addictions, including nicotine. However, one of the most commonly
perceived limitations with regard to its dissemination into community settings is
whether this protocol could be equally effective for treating patients across
different income levels. OBJECTIVE: This study aimed to examine whether
individuals' income levels affect treatment success in a cognitive behavioral
treatment (CBT) that included a voucher-based CM protocol for smoking cessation.
METHODS: A total of 92 treatment-seeking smokers in a community setting were
randomly assigned to a CBT group (N = 49) or to a CBT plus CM group (N = 43). The
CM procedure included a voucher program through which smoking abstinence was
reinforced on a schedule of escalating magnitude of reinforcement with a reset
contingency. We analyzed the impact of self-reported monthly income, alone and in
combination with treatment condition, on short-term (treatment retention) and
long-term (self-reported number of days of continuous smoking abstinence at 6
month follow-up) results. RESULTS: Income had no effect on treatment retention
and continuous abstinence outcomes at 6-month follow-up in either treatment
condition. Treatment modality emerged as the only significant predictor of
treatment success. CONCLUSIONS: Our findings suggest that treatment-seeking
smokers from the general population respond equally well to CM regardless of
their income levels. The results of this randomized controlled trial support the
generalizability of this evidenced-based program into community settings.
PMID- 28426356
TI - Focus Group Findings of Smoking Onset Among Male Youth in China.
AB - BACKGROUND: Adolescence is associated with smoking initiation among men in China.
The lack of qualitative studies using Chinese adolescent samples can pose
challenges to enacting effective smoking prevention messages that resonate with
male Chinese teenagers' thoughts, needs, and wishes. OBJECTIVE: This focus group
study was designed to obtain in-depth contextual information on early smoking
among male teenagers in China. METHODS: Twenty focus groups of 7-10 male students
from vocational and junior colleges (N = 165) were conducted, approximately half
in Shanxi and half in Guangdong. RESULTS: A large number of early smoking
activities occurred in homes and schools, and teenagers considered school toilets
and dorms safe havens for smoking. Many participants' first cigarettes were
offered to them by peers, others first smoked during social interactions, and
some started smoking of their own volition. Teenagers were curious about the
attributes of cigarette products, smoking techniques, and physical reactions.
More participants disclosed negative first smoking experiences than positive
experiences. Negative first physical experiences motivated some participants to
acquire better smoking techniques. Smoking experimentation was sustained in part
by reciprocated cigarette offers. Heavy experimentation occurred before
graduation from high school. Conclusions/Importance: The current findings provide
an empirical basis for developing intervention strategies that are alternative or
complementary to the current conventional health education. These strategies
include cognitive response methods to enhance antismoking beliefs, smoke-free
social interaction norms, and school-based (e.g., peer education) and home-based
(e.g., involving family members) intervention programs.
PMID- 28426357
TI - A Qualitative Assessment of Alcohol Consumption and Sexual Risk Behaviors Among
Men Who Have Sex With Men and Transgender Women in Peru.
AB - BACKGROUND: Peruvian men who have sex with men (MSM) and transgender women (TGW)
experience the double burden of a highly concentrated HIV epidemic with a high
prevalence of alcohol use disorders (AUDs). Recent research has associated both
with risky sexual behaviors, including unprotected sex, having multiple sexual
partners, engaging in sex work, having recent sexually transmitted infections,
and having HIV-infected partners. AUDs have also been associated in MSM/TGW with
being unaware of HIV+ status. OBJECTIVES: This study aims to further examine
issues associated with alcohol consumption, HIV infection, and risk behaviors in
a qualitative analysis of focus groups conducted with MSM/TGW in Peru. METHODS: A
total of 26 MSM/TGW participants with AUDs participated in three semi-structured
focus groups in Lima, Peru. Content analysis was facilitated by software, and
specific themes were elucidated. RESULTS: Participants described their drinking
patterns, including the types of alcoholic drinks they consumed. They depicted
drinking frequently and over multiple-day sessions. Problematic drinking
behaviors were described, as well as the perceived characteristics of alcohol
dependence. Interestingly, HIV-infected participants who were prescribed
antiretroviral therapy did not believe that their drinking affected their
medication adherence. These insights can aid in the design of future
interventions aiming to reduce problematic drinking as well as HIV-related risk
behaviors and, subsequently, HIV incidence. CONCLUSIONS: Peruvian MSM/TGW exhibit
problematic drinking, which may be associated with risky sexual behaviors and HIV
transmission. Interest in reducing alcohol consumption was high, suggesting the
need for targeted behavioral and pharmacological interventions.
PMID- 28426359
TI - Reductions in Hard Drug Use Among Homeless Youth Receiving a Strength-Based
Outreach Intervention: Comparing the Long-Term Effects of Shelter Linkage Versus
Drop-in Center Linkage.
AB - OBJECTIVES: The current study sought to test hard drug use outcomes for youth
receiving a strengths-based outreach and advocacy intervention that linked youth
to either a shelter or a drop-in center. METHODS: Homeless youth (14-24 years
old) were engaged by research assistants (RAs) at soup kitchens, parks,
libraries, and other locations that homeless youth were known to frequent. Youth
were randomly assigned to receive six months of advocacy that focused on linking
youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). Follow-up
assessments were conducted at 3, 6, and 9 months post-baseline. Hard drug use
over time was the main outcome. Intervention condition and service connection
were used as predictors for the baseline level and the slope of change in hard
drug use over time. Data analysis was conducted with Bernoulli Hierarchical
Generalized Linear Modeling in HLM7. RESULTS: The current study found that those
who were in the drop-in linkage condition exhibited a greater reduction in their
odds of using hard drugs during the follow-up points than their counterparts in
the shelter linkage condition. And finally, those who utilized services more
often during the follow-ups were those who exhibited less hard drug use at
baseline and less reduction in their odds of using hard drugs. CONCLUSIONS: This
study suggests that drop-in centers, which are often characterized by low-demand
programming and few behavioral restrictions, are effective for addressing hard
drug use among homeless youth.
PMID- 28426358
TI - Effects of Workplace Generalized and Sexual Harassment on Abusive Drinking Among
First Year Male and Female College Students: Does Prior Drinking Experience
Matter?
AB - BACKGROUND: Workplace harassment, a known risk factor for adult drinking, is
understudied in college samples, but may help explain observed gender differences
in drinking patterns. OBJECTIVE: We examine effects of sexual and generalized
workplace harassment on changes in drinking behavior over the first semesters of
college, and the extent to which these effects differ based on prematriculation
drinking for men and women students. METHOD: Data derive from two waves of a
longitudinal study of eight Midwestern colleges and universities. Data were
collected from 2080 employed students via a Web-based survey assessing sexual and
generalized workplace harassment, stressful life events, drinking to
intoxication, and binge drinking prior to freshman year (fall 2011) and
approximately one year later (summer to fall 2012). At baseline, lifetime
drinking status, frequency of alcohol consumption, and demographics were also
assessed. RESULTS: Linear-mixed modeling indicated that employed women students
who were frequent drinkers prematriculation were at risk for high levels of
drinking associated with workplace harassment, while men who were nondrinkers
were most at risk of increasing problem drinking over time when exposed to
workplace harassment. CONCLUSIONS: Alcohol use prevention efforts directed
towards employed students are needed both prior to and during college, to
instruct students how to identify workplace harassment and cope in healthier ways
with stressful workplace experiences. These efforts might be particularly useful
in stemming problematic drinking among women who drink frequently prior to
college, and preventing men who are nondrinkers upon college entry from
initiating problematic drinking during subsequent enrollment years.
PMID- 28426360
TI - Pharmaceutical Cognitive Enhancement in Greek University Students: Differences
Between Users and Non-Users in Social Cognitive Variables, Burnout, and
Engagement.
AB - Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of
prescribed medication for the improvement of cognitive functioning and academic
performance. Although there are some studies about PCE prevalence, it is less
clear how users and non-users of PCE substances differ with respect to their
positive and negative student experiences (e.g. academic burnout and engagement
with studies) and in social cognitive variables that relate to decision-making
and self-regulation of PCE use. The present study assessed whether students with
different experiences of PCE substance use displayed differences in academic
burnout, study engagement, and social cognitive variables relevant to PCE use.
Three hundred and forty-seven university students (mean age (M) = 22.15 years, SD
= 1.69; 54% females) completed a battery of anonymous questionnaires on academic
burnout, engagement with studies, social cognitive variables relevant to PCE use,
and self-reported use of PCE substances and non-prescribed nutritional
supplements. Three user groups emerged, namely non-users (51.9%, n = 180), single
users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of
both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate
analysis of variance indicated significant differences among the three user
groups in intentions, attitudes, social norms, and anticipated regret toward PCE
use. No significant differences were observed with respect to academic burnout
and work engagement. The findings show that university students may engage in PCE
use independent of their student experiences. Rather, a chemically assisted
performance enhancement mindset seems to differentiate users from non-users of
PCE substances.
PMID- 28426362
TI - Predicting Change in an Integrated Dual Diagnosis Substance Abuse Intensive
Outpatient Program.
AB - Research on routine outcome monitoring in psychotherapy settings is plentiful but
not without implementation obstacles. In fact, there is a relative dearth of real
time outcome monitoring in substance use treatment settings. Numerous barriers to
the development and implementation of clinical decision support tools and outcome
monitoring of substance use patients, including the need to establish expected
trajectories of change and use of reliable change indices have been identified
(Goodman, McKay, & DePhilippis, 2013 ). The current study was undertaken to
develop expected trajectories of change and to demonstrate the treatment
effectiveness of a dual diagnosis intensive outpatient program. The expected
trajectories of change for days of substance use and depression scores were
developed using predictive equation models from derivation samples and then
applied to cross-validation samples. Predictive equations to monitor substance
use were developed and validated for all patients and for only patients who were
actively using substance at the time of admission, as well as to monitor severity
of their depression symptom on a weekly basis. Validation of the equations was
assessed through the use of Cohen's kappa (kappa), receiver operating
characteristic curves, reliable change index, and percentage improvement. Large
effect sizes for reductions in substance use (Cohen's d = .76) and depressive
symptoms (d = 1.10) are reported. The best predictive models we developed had
absolute accuracy rates ranging from 95 to 100%. The findings from this study
indicate that predictive equations for depressive symptoms and days of substance
use can be derived and validated on dual diagnosis samples.
PMID- 28426361
TI - Sociodemographic and Substance Use Disorder Determinants of HIV Sexual Risk
Behavior in Men and Women in Outpatient Drug Treatment in the NIDA National Drug
Abuse Treatment Clinical Trials Network.
AB - BACKGROUND: Sexual risk behavior is now the primary vector of HIV transmission
among substance users in the United States with gender as a crucial moderator of
risk behavior. OBJECTIVES: The purpose of this study was to examine gender
differences in factors (age, race/ethnicity, education) that predict main-partner
unprotected sexual occasions (USO) using the unique platform of two parallel NIDA
National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex
intervention trials. METHODS: Baseline assessments of male (N = 430) and female
(N = 377) participants included demographic characteristics; past 3-month sexual
activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid
use disorders. Using mixed effects generalized linear modeling of the main
outcome USO, two-way interactions of gender with age, race/ethnicity, and
education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid
use disorder. RESULTS: When adjusted for alcohol use disorder, the interaction of
education and gender was significant. For men, a high school or greater education
was significantly associated with more USO compared to men with less than high
school. For women, greater than high school education was significantly
associated with less USO compared to women with a high school education. None of
the other interactions were significant when adjusted for cocaine/stimulant or
opioid use disorder. Conclusions/Importance: This study demonstrates gender
differences in the relationship of education, alcohol use disorder, and main
partner USO in individuals in substance abuse treatment. This underscores the
importance of considering demographic and substance use factors in HIV sexual
risk behavior and in crafting prevention messages for this population.
PMID- 28426363
TI - Social Risk and Protective Factors in Adolescents' Reduction and Cessation of
Alcohol Use.
AB - BACKGROUND: Adolescents' alcohol use is related to many health problems,
injuries, and violent acts, some with fatal consequences. A gap exists in the
literature discussing risk/protective factors in change from non-heavy drinking
to non-drinking, and also for change from heavy drinking to non-heavy drinking or
non-drinking. OBJECTIVE: This secondary study examined some risk and protective
factors involved when adolescent non-heavy drinkers and adolescent heavy drinkers
curb or terminate their drinking. METHOD: The temporal-ordered analysis evaluated
570 nonheavy drinkers and 374 heavy drinkers (all adolescents), a sample
extracted from Wave 1 and Wave 2 of the National Longitudinal Study of Adolescent
to Adult Health, or Add Health. RESULTS: We observed positive associations
between likelihood of change from heavy/non-heavy drinking to nondrinking and 5
characteristics: neighborhood attachment, maternal receipt of public assistance,
African American ethnicity, maternal involvement, physical maltreatment,
depressive feelings, and substance-abuse treatment. We observed negative
associations between this outcome and peer drinking, delinquent behaviors, drug
use, and emotional maltreatment. Positive associations were found between
likelihood of change from heavy drinking to non-heavy drinking and both maternal
involvement and depressive feelings, while a negative association was found
between this outcome and delinquent behaviors. CONCLUSIONS: Reduction/cessation
interventions should, at the individual level, focus on ending adolescent
drinkers' associations with alcohol-using and delinquent peers. Interventions
require supportive roles for parents, schools, and communities.
PMID- 28426365
TI - Moderators of the Effects of Alcohol Protective Behavioral Strategies: Three
Attempts of Replication and Extension.
AB - BACKGROUND: Protective behavioral strategies (PBS) can be used to reduce alcohol
related harm when drinking. Despite much research demonstrating that use of
protective behavioral strategies (PBS) is associated with decreased alcohol
use/problems, few studies have examined moderators of these associations.
Moderation tests are important as they define the boundary conditions of the
protective effects of PBS use (i.e., identify for whom and in what context PBS
use reduces harm). OBJECTIVES: We aimed to replicate and extend the findings from
three published studies that have examined putative moderators of PBS-alcohol
associations: self-regulation, negative urgency, and drinking refusal self
efficacy. METHOD: Participants were recruited from a psychology department
participant pool at a large, southwestern university in the United States (N =
628). RESULTS: Although we replicated most main effects and bivariate
correlations, we failed to replicate any of the moderation effects (i.e.,
interaction effects). Conclusions/Importance: We urge PBS researchers to attempt
to replicate moderation effects in independent samples to determine these
effects' reproducibility. Limitations and future directions are discussed.
PMID- 28426364
TI - Patterns of Mood and Personality Factors and Associations With STI/HIV-Related
Drug and Sex Risk Among African American Male Inmates.
AB - BACKGROUND: Research on the association between antisocial personality disorder
(ASPD) with comorbid mental disorders and sexually transmitted infection
(STI)/HIV risk among inmates is scant despite the high prevalence of
psychopathology and of STI/HIV in this population. METHODS: We used baseline data
from Project DISRUPT, a cohort study conducted among incarcerated African
American men (n = 207), to measure associations between ASPD and STI/HIV risk. We
also conducted latent class analyses (LCAs) to identify subgroups defined by ASPD
with comorbid stress, depression, and borderline personality disorder symptoms
and measured associations between latent class membership and STI/HIV risk.
RESULTS: Approximately 15% had ASPD and 39% reported depression. Controlling for
sociodemographics, stress, and depression, ASPD was independently associated with
illicit [AOR = 3.23, 95% confidence interval (CI): 1.18-8.87] and injection drug
use (AOR: 5.49, 95% CI: 1.23-24.42) but not with sexual risk. LCAs suggested that
those at high risk of ASPD were likely to experience co-morbid mental disorders.
ASPD comorbid with these disorders was linked to drug and sex risk. CONCLUSIONS:
STI/HIV prevention for inmates should incorporate diagnosis and treatment of ASPD
and comorbid disorders, and interventions to address ASPD-related factors (e.g.,
impulsivity) that drive STI/HIV risk.
PMID- 28426366
TI - Notch1 induces endothelial senescence and promotes tumor progression.
PMID- 28426367
TI - Child and Adolescent Emergency and Urgent Mental Health Delivery Through
Telepsychiatry: 12-Month Prospective Study.
AB - BACKGROUND: The significant gap between children and adolescents presenting for
emergency mental healthcare and the shortage of child and adolescent
psychiatrists constitutes a major barrier to timely access for psychiatric
assessment for rural and remote areas. Unlike remote areas, urban emergency
departments have in-house psychiatric consultation. Telepsychiatry may be a
solution to ensure the same service for remote areas. However, there is a paucity
of studies on the use of telepsychiatry for child and adolescent emergency
consults. Thus, the aim of our study was to (1) assess patient satisfaction with
telepsychiatry and (2) compare clinical characteristics and outcome of
telepsychiatry with face-to-face emergency child and adolescent assessments.
METHODS: This is a prospective study of telepsychiatry emergency assessments of
children and adolescents referred by emergency physicians. The comparison group
was age- and gender-matched patients seen for face-to-face urgent assessments.
Data were gathered on demographic and clinical variables. Telepsychiatry
satisfaction was assessed using a questionnaire. Descriptive statistics and chi
square tests were used to assess group differences for each variable. Logistic
regression was used to assess impact of the variables on outcome after the
consult. A p value <0.05 was used to determine statistical significance. RESULTS:
Sixty (n = 60) assessments were conducted through telepsychiatry in 12 months.
Among the telepsychiatry group, Aboriginal patients were over-represented (50%
vs. 6.7%, p < 0.001), a higher proportion received a diagnosis of adjustment
disorder (22% vs. 8.3%, p = 0.004) or no diagnosis (27% vs. 6.7%, p = 0.004)
compared with controls. There was no statistically significant difference between
groups on other clinical variables. Patients reported a high degree of
satisfaction with telepsychiatry. CONCLUSIONS: Telepsychiatry is acceptable to
patients and families for safe emergency assessment and follow-up, reducing
unnecessary travel to urban centers. Longer time outcomes are needed to establish
validity of telepsychiatry for emergency assessments.
PMID- 28426368
TI - Living in the epilepsy treatment gap in rural South India: A focused ethnography
of women and problems associated with stigma.
AB - In India, women with epilepsy face unique challenges. A focused ethnography of
six women within the epilepsy treatment gap was conducted in rural South India.
Women were asked to describe their day-to-day lives. Data were collected through
open-ended, semistructured interview questions, participant observation, and
field notes. Thematic analysis was done. The disease-related stigma contributed
to the women's physical, psychological, and emotional struggles; the women and
their family members made every effort to conceal the disease. Educational
interventions to create awareness could help women seek effective treatments for
their seizures, thereby reducing the stigma and improving the quality of their
lives.
PMID- 28426370
TI - PIN-formed protein, a door to reveal the mechanism for auxin-triggered initiation
of cotton fiber.
AB - Cotton fibers are differentiated ovule epidermal cells that provide an ideal
model to study cell differentiation and elongation. Establishment of auxin
maximum in fiber cells is crucial for cotton-fiber protrusion from ovule surface.
However, it is unclear where the auxin originates from and how the auxin
accumulates in fiber cells. Our recent results indicate that the auxin is mainly
imported from the outside of ovules, and transported to fiber cells through GhPIN
(homolog of PIN-formed proteins in cotton) -mediated polar auxin transport,
rather than in situ synthesis. Based on our finding in GhPINs, we discuss here
briefly how auxin flow to fiber cells and auxin gradient in ovule epidermis is
established mainly by GhPIN3a protein.
PMID- 28426369
TI - HOS1 acts as a key modulator of hypocotyl photomorphogenesis.
AB - Plants recognize light as an environmental signal to determine the proper timing
of growth and development. In Arabidopsis seedlings, hypocotyl growth is promoted
in the dark but suppressed in the light. It is known that the red/far-red light
sensing receptor phytochrome B (phyB) suppresses the function of PHYTOCHROME
INTERACTING FACTOR (PIF) transcription factors, which act as photomorphogenic
repressors. However, molecular mechanisms underlying the phyB-mediated inhibition
of PIF functioning remain unclear. We recently demonstrated that HIGH EXPRESSION
OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) facilitates the phyB-mediated
suppression of PIF4 during the light period to achieve hypocotyl
photomorphogenesis. HOS1 inhibits the transcriptional activation activity of PIF4
by forming protein complexes. Notably, phyB-mediated light signals induce HOS1
activity, thus promoting hypocotyl photomorphogenesis. While HOS1 is known to act
as an E3 ubiquitin ligase or a chromatin remodeling factor, our data illustrate a
novel role of HOS1: it acts as a component of phyB-mediated light signaling in
hypocotyl photomorphogenesis.
PMID- 28426372
TI - Continuing Education-"The Action Level"(r).
AB - Access "The Action Level"(r) Questions online at:
http://www.acgih.org/products/joeh/alquestions.htm Access "The Action Level"(r)
Answers online at: http://www.acgih.org/products/joeh/alanswers.htm Access "The
Action Level"(r) Registration Form online at:
https://www.acgih.org/products/joeh/alregfrm.htm "The Action Level,"(r) a self
study, continuing education program, provides a convenient and interesting
opportunity for individuals to expand their knowledge in relevant areas of
industrial hygiene, as well as occupational and environmental safety and health.
The program is approved by both the American Board of Industrial Hygiene, and the
Board of Certified Safety Professionals, which award Certification Maintenance
(CM) points and Continuance of Certification (COC) points, respectively, for
successful participation. Participants must read each issue of the Journal,
answer "The Action Level"(r) questions, and return the completed answer sheet at
the end of that issue's "The Action Level"(r) column. To earn the designated CM
or COC credit, a score of 70 percent or better is required within a 12-month
period. Certified Industrial Hygienists and Certified Associate Industrial
Hygienists may earn 2 points per year. Certified Safety Professionals may earn
1.2 points per year. Enrollment is possible each month, but points are awarded
only four times each year-in March, June, September, and December-to participants
who score an average of 70 percent or better within each three-month period. If
you register in September 2009, you will not receive CM points and/or COC points
until the following quarter. In the next quarter, you'll receive 0.5 CM points
and/or 0.3 COC points after satisfactorily completing answer sheets for the
October, November and December 2009 issues, and so on. To enroll, complete the
registration form and the answer sheet at the end of this "The Action Level"(r)
column. The cost is $199 (ACGIH(r)/AIHA members)/$219 (nonmembers) for one year.
Nonmembers are encouraged to become members to take advantage of the member
discount. For more information regarding ACGIH(r) membership, call 513-742-2020,
or apply on-line at http://www.acgih.org/members/memberform.htm . Checks must be
in U.S. currency, drawn on a U.S. bank, and payable to ACGIH(r). We also accept
AmEx, MasterCard, Discover and Visa. This continuing education program fee is
separate from the Journal subscription cost. The fee covers administration costs,
and is nonrefundable. Submissions must be received by the date listed on each
answer sheet.
PMID- 28426371
TI - * Optimization of Preculture Conditions to Maximize the In Vivo Performance of
Cell-Seeded Engineered Intervertebral Discs.
AB - The development of engineered tissues has progressed over the past 20 years from
in vitro characterization to in vivo implementation. For musculoskeletal tissue
engineering in particular, the emphasis of many of these studies was to select
conditions that maximized functional and compositional gains in vitro. However,
the transition from the favorable in vitro culture environment to a less
favorable in vivo environment has proven difficult, and, in many cases,
engineered tissues do not retain their preimplantation phenotype after even short
periods in vivo. Our laboratory recently developed disc-like angle-ply structures
(DAPS), an engineered intervertebral disc for total disc replacement. In this
study, we tested six different preculture media formulations (three serum
containing and three chemically defined, with varying doses of transforming
growth factor beta3 [TGF-beta3] and varying strategies to introduce serum) for
their ability to preserve DAPS composition and metabolic activity during the
transition from in vitro culture to in vivo implantation in a subcutaneous
athymic rat model. We assayed implants before and after implantation to determine
collagen content, glycosaminoglycan (GAG) content, metabolic activity, and
magnetic resonance imaging (MRI) characteristics. A chemically defined media
condition that incorporated TGF-beta3 promoted the deposition of GAG and collagen
in DAPS in vitro, the maintenance of accumulated matrix in vivo, and minimal
changes in the metabolic activity of cells within the construct. Preculture in
serum-containing media (with or without TGF-beta3) was not compatible with DAPS
maturation, particularly in the nucleus pulposus (NP) region. All groups showed
increased collagen production after implantation. These findings define a
favorable preculture strategy for the translation of engineered discs seeded with
disc cells.
PMID- 28426373
TI - Immortal Life of the Common Rule: Ethics, Consent, and the Future of Cancer
Research.
PMID- 28426374
TI - Perioperative Hepatic Arterial Infusion Pump Chemotherapy Is Associated With
Longer Survival After Resection of Colorectal Liver Metastases: A Propensity
Score Analysis.
AB - Purpose To investigate whether perioperative hepatic arterial infusion pump
chemotherapy (HAI) was associated with overall survival (OS) in patients who had
a complete resection of colorectal liver metastases (CLM). Methods Patients who
underwent a complete resection of CLM between 1992 and 2012 were included from a
single-center prospectively maintained database. All patients who received HAI
also received perioperative systemic chemotherapy. Propensity score analysis was
used to match patients for seven known prognostic factors. Results A total of
2,368 consecutive patients underwent a complete resection of CLM, with a median
follow-up of 55 months. The median OS for patients with HAI (n = 785) was 67
months versus 44 months without HAI (n = 1,583; P < .001), despite more advanced
disease in the HAI group. OS at 10 years was 38.0% versus 23.8% without HAI. For
patients who received modern systemic chemotherapy (n = 1,442), the median OS was
67 months with HAI and 47 months without HAI ( P < .001). The hazard ratio
adjusted by propensity score demonstrated longer OS with HAI: 0.67 (95% CI, 0.59
to 0.76; P < .001). A pronounced difference in median OS was found for patients
with node-negative colorectal cancer (129 months with HAI v 51 months without; P
< .001) and a low clinical risk score of 0 to 2 points (89 months with HAI v 53
months without; P < .001). Conclusion Patients who received HAI had a median OS
of approximately 2 years longer than patients without HAI. The strong association
was independent of the use of modern systemic chemotherapy and remained in
propensity score analysis. Patients with node-negative primary tumors or a low
clinical risk score seemed to benefit most from HAI.
PMID- 28426375
TI - United States Population-Based Estimates of Patient-Reported Outcomes Measurement
Information System Symptom and Functional Status Reference Values for Individuals
With Cancer.
AB - Purpose To estimate cancer population-based reference values in the United States
for eight PROMIS (Patient-Reported Outcomes Measurement Information System)
domains by age and stage of disease. Patients and Methods For the Measuring Your
Health (MY-Health) study, persons newly diagnosed with cancer (prostate,
colorectal, non-small-cell lung, non-Hodgkin lymphoma, breast, uterine, or
cervical) from 2010 to 2012 (N = 5,284) were recruited through the National
Cancer Institute's SEER Program. Participants were mailed surveys 6 to 13 months
after diagnosis. Raking by race/ethnicity, age, and stage generated weighted
average PROMIS scores for pain interference, fatigue, anxiety, depression, sleep
disturbance, physical function, ability to participate in social roles, and
cognitive function. PROMIS measures are standardized to a T-score metric, with a
score of 50 representing the general US population mean. Clinically meaningful
differences were defined as a 3-point difference in scores. Results Several
reference values (means) for patients with cancer were worse than the general
United States population norms of 50. These include pain interference (52.4),
fatigue (52.2), and physical function (44.1). Reference values were highest (ie,
showed greatest symptom burden) in lung cancer (pain interference, 55.5; fatigue,
57.3; depression, 51.4) and cervical cancer (anxiety, 53.2; sleep disturbance,
53.4). Reference values for patients age 65 to 84 years reported lower sleep
disturbance, anxiety, and depression, and better cognitive function than younger
patients. Cancer reference values were poorer among those with advanced disease
compared with patients with limited or no evidence of disease, specifically
physical function (41.1 v 46.6, respectively), fatigue (55.8 v 50.2,
respectively), and pain interference (55.2 v 50.9, respectively). Conclusion In a
large, population-based sample of patients with recently diagnosed cancer, we
observed symptom severity and functional deficits by age, stage, and cancer type
consistent with the expected impact of cancer diagnosis and treatment. These
United States cancer reference values can help facilitate interpretation of the
PROMIS domain scores in research studies or in clinical applications that measure
and evaluate the symptom and functional burden patients with cancer experience
after initial treatment.
PMID- 28426376
TI - Evaluation of Different Laser-Supported Surgical Protocols for the Treatment of
Oral Leukoplakia: A Long-Term Follow-Up.
AB - PURPOSE: The aim of this study was to evaluate the long-term success rate of oral
leukoplakia treatments by using different laser-supported surgical protocols.
PATIENTS AND METHODS: Overall, 2347 diagnosed homogeneous oral leukoplakias were
treated with CO2 laser and were included in this study. Different surgical
protocols (P) were used: P1 (SV = superficial scanning) was a complete
superficial vaporization of the leukoplakia by a scanning mode in two passages
respecting an overlapping. Only the visible white area was treated in one
surgical session independently of the lesion size. P2 (CR1x1) was a complete
excision of the lesions until a tissular depth of 1 mm and 1 mm of surrounding
healthy-like tissue were attained. The visible white area was treated in one
surgical session independently of the lesion size. P3 (CR1x3) was a complete
excision of the lesions until a minimum tissue depth of 1 mm and 3 mm of
surrounding healthy-like tissue were obtained. The visible white area was treated
in one surgical session independently of the lesion size. P4 (PR1x3) was similar
to the third one, but for patient comfort, the large lesions of leukoplakias
(lesion size higher than 20 mm), the complete surgical excision of the
leukoplakia was performed in multiple sessions that were spaced by 1 month
(partial surgical removal of 10 mm per session). All patients were recalled at 2
and 8 weeks after surgery, and then every 2 months during the first year, every 4
months during the second year, and once a year for the follow-up period of 6
years. A biopsy was done once a year during the follow-up period in the surgical
site when needed. The control consisted of checking the nature and the aspect of
the healed mucosa to exclude an eventual recurrence of leukoplakia. RESULTS: The
percentage of permanent success after 6 years of follow-up was 5.7%, 69.7%,
97.8%, and 71.9%, respectively, for the first surgical protocol (SV), the second
(CR 1 * 1), the third (CR 1 * 3), and the fourth (PR 1 * 3). The appearance of
malignant transformation after laser treatment (during the follow-up period of 6
years) was 20%, 1%, and 0.2%, respectively, for the groups treated by the
following protocols: 1 (SV), 2 (CR 1 * 1), and 4 (PR 1 * 3). Only in the third
group CR1x3, no dysplasia or malignant transformation was noted. On the contrary,
the appearance of malignant transformation in failed treated cases was 21.21% for
the protocol 1 (SV), 3% for the protocol 2 (CR 1 * 1), and 0.6% for the protocol
4 (PR 1 * 3). CONCLUSIONS: The results of this long-term follow-up of treated
patients with oral homogeneous leukoplakias pointed out that the surgical laser
protocol respecting the complete excision of leukoplakias, in one session, by the
removal of a minimum of 1 mm in lesion depth and 3 mm of surrounding healthy-like
tissues (CR 1 * 3) offers significantly the highest success rate.
PMID- 28426377
TI - Development of the Sports Organization Concussion Risk Assessment Tool (SOCRAT).
AB - OBJECTIVE: In this paper, we describe the development of a novel tool-the Sports
Organization Concussion Risk Assessment Tool (SOCRAT)-to assist sport
organizations in assessing the overall risk of concussion at a team level by
identifying key risk factors. METHODS: We first conducted a literature review to
identify risk factors of concussion using ice hockey as a model. We then
developed an algorithm by combining the severity and the probability of
occurrence of concussions of the identified risk factors by adapting a risk
assessment tool commonly used in engineering applications. RESULTS: The following
risk factors for ice hockey were identified: age, history of previous
concussions, previous body checking experience, allowance of body checking, type
of helmet worn and the game or practice environment. These risk factors were
incorporated into the algorithm, resulting in an individual risk priority number
(RPN) for each risk factor and an overall RPN that provides an estimate of the
risk in the given circumstances. CONCLUSION: The SOCRAT can be used to analyse
how different risk factors contribute to the overall risk of concussion. The tool
may be tailored to organizations to provide: (1) an RPN for each risk factor and
(2) an overall RPN that takes into account all the risk factors. Further work is
needed to validate the tool based on real data.
PMID- 28426378
TI - Ostracism and physiological arousal following traumatic brain injury.
AB - PRIMARY OBJECTIVE: This study aimed to examine the psychological and
physiological effects of ostracism in adults with traumatic brain injury (TBI).
RESEARCH DESIGN: A within-subject, counterbalanced design was used. The two
conditions, inclusion and ostracism, were examined across two groups (between
subjects). METHODS AND PROCEDURES: A group of 21 adults with TBI and 17 matched
controls participated in the Cyberball paradigm. This task is a computerised task
that exposes participants to a game of catch and throw. In the inclusion
condition they are included fairly in the game, while in the ostracism condition
they are excluded from the game following the first few throws. Skin conductance
levels (SCLs) were measured throughout the game as a proxy for social stress.
MAIN OUTCOMES: Results showed that people with TBI were cognitively aware of when
they are being ostracised, but that their self-reported emotional experience to
social exclusion was different to that of the control group. Differences in SCLs
between groups and between conditions did not reach significance nor did they
correlate with behavioural responses. CONCLUSIONS: These findings are discussed
in terms of the consequences of dissociation between psychological and
physiological responses and the implications for motivating behaviours associated
with re-inclusion.
PMID- 28426380
TI - The Henry Stonnington Award for best review paper published in Brain Injury 2016.
PMID- 28426381
TI - Hyperbaric oxygen for experimental intracerebral haemorrhage: Systematic review
and stratified meta-analysis.
AB - OBJECTIVE: Hyperbaric oxygen (HBO) is widely used in treating various
neurological diseases. However, HBO for treatment of intracerebral haemorrhage
(ICH) remains controversial, in either animal or clinical studies. Therefore, we
conducted this systematic review and meta-analysis on studies describing the
efficacy of HBO in animal models of ICH. METHODS: Studies were identified by
searching mainstream databases through November 2015. The efficacy of HBO in
animal models of ICH was assessed by changes in the brain water content (BWC),
neurobehavioural outcome (NO) or both. Subgroup analyses were performed according
to different design characteristics. RESULTS: In total 15 studies met our
inclusion criteria. HBO can reduce the BWC (-0.982, 95% CI, -1.148 to -0.817; P <
0.01; 57 comparisons), and improve NO (-0.767, 95% CI, -1.376 to -0.159; P <
0.01; eight comparisons). HBO was most effective in reducing BWC when given 72 h
after ICH for a 4- to 5-day consecutive treatment at the chamber pressure of 3.0
atmosphere absolute. Efficacy was higher with phenobarbital anaesthesia, the
blood infusion model and in rabbits. CONCLUSION: Although HBO was found to be
effective in experimental ICH, additional confirmation is needed due to possible
publication bias, poor study quality and the limited number of studies conducting
clinical trials.
PMID- 28426382
TI - Effectiveness of hand washing on the removal of iron oxide nanoparticles from
human skin ex vivo.
AB - In this study, the effectiveness of washing with soap and water in removing
nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (alpha
Fe2O3) or maghemite (gamma-Fe2O3) powder, with primary particle diameters between
20-30 nm, were applied to two samples each of fresh and frozen ex vivo human skin
in two independent experiments. The permeation of nanoparticles through skin, and
the removal of nanoparticles after washing with soap and water were investigated.
Bare iron oxide nanoparticles remained primarily on the surface of the skin,
without penetrating beyond the stratum corneum. Skin exposed to iron oxide
nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively,
of the original dose after washing. In the event of dermal exposure to chemicals,
removal is essential to avoid potential local irritation or permeation across
skin. Although manufactured at an industrial scale and used extensively in
laboratory experiments, limited data are available on the removal of engineered
nanoparticles after skin contact. Our finding raises questions about the
potential consequences of nanoparticles remaining on the skin and whether
alternative washing methods should be proposed. Further studies on skin
decontamination beyond use of soap and water are needed to improve the
understanding of the potential health consequences of dermal exposure to
nanoparticles.
PMID- 28426383
TI - Contribution of sucrose transporters to phloem unloading within Sorghum bicolor
stem internodes.
AB - Sucrose produced in source leaves is loaded into collection phloem, transported
to sinks and unloaded for utilization or storage. In the context of long distance
transport, sucrose transporters (SUTs) can function to load sucrose into
collection phloem, retrieve leaked sucrose during long distance transport, and
load sucrose into sink cells. SUTs have also been proposed to efflux sucrose
under conditions of low proton motive force and low extracellular sucrose. The
involvement of sucrose transporters in phloem unloading in a representative
monocot stem, Sorghum bicolor, was evaluated during different stages of internode
development. Transcript levels and functional properties of selected key
transporters were measured, with both cellular and subcellular localization
determined.
PMID- 28426384
TI - A 2-year-old boy with circulatory failure owing to streptococcal toxic shock
syndrome: case report.
AB - A 2-year-old boy presented with severe hypotension and acute kidney injury after
a prodrome of non-bloody diarrhoea and fever in the preceding 3 days. He had a
mild Ebstein cardiac anomaly but otherwise a normal past history and growth. On
examination, he looked ill, his temperature was 37.5 degrees C, circulation was
poor, and there were several purpuric lesions on the face, hands and scrotum.
Haemoglobin was 7.8 g/dL (11-14), total white cell count 27 * 109/L, platelets 62
* 109/L, blood urea nitrogen 20.7 mmol/L (4.2-17.1), serum creatinine 95.4
MUmol/L (21.2-36.2), CRP 154 mg/L (<5), AST 296 U/L (11-50), ALT 909 U/L (7-40)
and C3 component of complement 0.8 g/L (0.9-1.8). Activated partial
thromboplastin time (APTT) and prothrombin time (PT) were prolonged and
fibrinogen level was 1.0 g/L (2-4). He received immediate fluid resuscitation (IV
0.9% saline solution, 2 * 10 ml/kg boluses, followed by glucose 5/0.45% sodium
chloride solution, 2 * 10 ml/kg) and antibiotics (ciprofloxacin and amikacin) but
circulation continued to deteriorate with development of decreased consciousness.
He was placed on mechanical ventilation and vasopressor agents were added.
Despite improved circulation over the next 2 days, he developed oliguria,
progressive fluid overload, generalised oedema and a right-sided pleural
effusion. Dialysis was commenced on day 3 of admission. Differential diagnosis
included sepsis, atypical haemolytic uraemic syndrome and lupus nephritis. Blood
and urine cultures remained negative but an anti-streptolysin O titre of 1318
(<200) IU/mL led to the diagnosis of streptococcal toxic shock syndrome which is
rare in early childhood and associated with high mortality. Haemodialysis was
commenced and continued for 10 days with successful treatment of fluid overload
and subsequent extubation. Renal function was completely restored over the
following 6 weeks and he was discharged in good clinical condition about 2 months
after intial admission. The clinical course and outcome are discussed, and the
importance of timely initiation of dialysis when there is fluid overload is
emphasised.
PMID- 28426385
TI - Birth in winter can reduce the risk of lung cancer: A retrospective study of the
birth season of patients with lung cancer in Beijing area, China.
AB - The season of birth is an important risk factor for several diseases. We explored
the relationship between birth season and lung cancer. In this population-based
retrospective study, we focused on patients with lung cancer who had registered
at the Beijing Institute for Cancer Research from 2003 to 2012. In total, 33,025
patients were divided into five subgroups based on their histologic
classification, and these five subgroups were compared with the general
population (i.e., the permanent resident population of Beijing in 2013). A binary
logistic regression method with sex and age as control factors was used to
evaluate the relationship between birth season and lung cancer; P < 0.01 was
statistically significant. Taking winter as a reference in our analysis of the
relationship between season of birth and lung cancer, we found that people who
were born in other seasons had a higher probability of developing lung cancer
(spring: odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.03-1.09;
summer: OR = 1.07, 95% CI = 1.04-1.10; autumn: OR = 1.06, 95% CI = 1.03-1.09) (P
< 0.01). Among the five subgroups, persons with squamous cell carcinoma who were
born in summer were more likely to develop lung cancer than those who were born
in winter (OR = 1.09, 95% CI = 1.02-1.15, P = 0.006). The other subgroups showed
no correlation with season of birth (P > 0.01). This study demonstrates that for
people born in winter, the risks of developing lung cancer and squamous cell
carcinoma are comparatively lower than those for people born in other seasons.
Differences in immune function and the maternal nutrition status during pregnancy
of people born in different seasons may explain this finding.
PMID- 28426386
TI - New Zealanders working non-standard hours also have greater exposure to other
workplace hazards.
AB - Exposure to workplace hazards, such as dust, solvents, and fumes, has the
potential to adversely affect the health of people. However, the effects of
workplace hazards on health may differ when exposure occurs at different times in
the circadian cycle, and among people who work longer hours or who do not obtain
adequate sleep. The aim of the present study was to document exposures to
workplace hazards across a national sample of New Zealanders, comparing people
who work a standard 08:00 -17:00 h Monday-to-Friday working week (Std hours) and
those who do not (N-Std hours). New Zealanders (n = 10 000) aged 20-64 yrs were
randomly selected from the Electoral Roll to take part in a nationwide survey of
workplace exposures. Telephone interviews were conducted between 2004 and 2006,
using a six-part questionnaire addressing demographics, detailed information on
the current or most recent job (including exposures to a range of workplace
hazards), sleep, sleepiness, and health status. N-Std hours were categorised on
the basis of: being required to start work prior to 07:00 h or finish work after
21:00 h and/or; having a regular on-call commitment (at least once per week)
and/or; working rotating shifts and/or; working night shift(s) in the last month.
The response rate was 37% (n = 3003), with 22.2% of participants (n = 656)
categorised as working N-Std hours. Industry sectors with the highest numbers of
participants working N-Std hours were manufacturing, health and community
services, and agriculture, fishing, and forestry. Response rate was 37% (n =
3003) with 22.2% (n = 656) categorised as working N-Std hours. Participants
working N-Std hours were more likely to be exposed to all identified hazards,
including multiple hazards (OR = 2.45, 95% CI = 2.01-3.0) compared to those
working Std hours. Participants working N-Std hours were also more likely to
report 'never/rarely' getting enough sleep (OR = 1.38, 95% CI = 1.15-1.65),
'never/rarely' waking refreshed (OR = 1.23, 95% CI = 1.04-1.47), and excessive
sleepiness (OR = 1.77, 95% CI = 1.29-2.42). New Zealanders working N-Std hours
are more likely to be exposed to hazards in the workplace, to be exposed to
multiple hazards, and to report inadequate sleep and excessive sleepiness than
their colleagues working a standard 08:00-17:00 h Monday-to-Friday working week.
More research is needed on the effects of exposure to hazardous substances
outside the usual waking day, on the effects of exposure to multiple hazards, and
on the combination of hazard exposure and sleep restriction as a result of shift
work.
PMID- 28426388
TI - If the Morning-Evening Questionnaire (MEQ) is able to predict the actigraphy
based acrophase, how does its reduced, five-item version (rMEQ) perform?
PMID- 28426387
TI - Characterization of bimodal chronotype and its association with sleep: A
population-based study.
AB - The circadian system coordinates internal events in a daily schedule to make sure
that the body systems are synchronized to environmental time and internal cues.
One important behavioral aspect of the circadian system is the chronotype. It is
usually assessed through subjective questionnaires, being the Horne-Ostberg
Morningness-Eveningness Questionnaire (MEQ) one of the most used. It classifies
individuals into three major categories: morning, evening, and intermediate
types. Recently, it has been hypothesized the existence of a fourth chronotype,
the bimodal type, through an algorithm derived from the MEQ responses. Bimodals
answer as morning-types in some questions, and as evening-types in others,
resulting in an intermediate total score. To better characterize this phenotype,
the present study aimed to detect and characterize the frequency of the bimodal
chronotype in the EPISONO, a large population-based cohort, as well as to verify
the association between bimodality and sleep parameters and genetic variation in
the PER3 gene. Of the 1,042 individuals who participated of the EPISONO, 857 had
MEQ filled correctly. We found that 16% of our sample were bimodal types. We
observed that bimodal individuals were significantly younger and had lower body
mass index. The association between PER3 VNTR genotype and gender with bimodal
chronotype was not significant. However, we found an association between
bimodality and Epworth Sleepiness Scale (EES) and apnea-hypopnea index (AHI). We
did not find a statistically significant difference between bimodals and
intermediate non-bimodals for the studied variables. Lastly, it was observed that
the most significant predictors for bimodal chronotype were female gender, AHI,
and EES. In conclusion, the present work provides more evidence that the bimodal
type might have to be considered when classifying chronotype and its association
with young age and sleepiness may be due to the influence of social and
environmental factors.
PMID- 28426389
TI - Melatonin and circadian rhythms in autism: Case report.
AB - Among the most co-occurring conditions in autism spectrum disorders (ASD), there
are sleep disorders which may exacerbate associated behavioral disorders and lead
to intensification of existing autistic symptoms. Several studies investigating
the use of melatonin in the treatment of sleep disorders in ASD have shown
comparative efficiency in sleep with little or no side effects. Here we report a
case of ASD with non-24-hour rhythm and the effect of melatonin in circadian
parameters by actigraphy. Visual analysis of the first 10 days recorded and the
periodogram suggest that this patient showed a non-24-hour rhythm. This ASD
subject showed before melatonin administration an activity/rest rhythm lower than
24 hours. The results show that melatonin increased approximately 4.7 times the
regularity of circadian activity rhythm and resting staying on average between
00:00 and 06:00 and showed positive effects in improving the quality of sleep and
behavior. So, the actigraphy showed an ASD subject with a non-24-hour
activity/rest rhythm which changed this rhythm to a 24-hour rhythm after
melatonin administration. This result reinforces the prospect of therapy with
melatonin for synchronization (increased regularity) of endogenous rhythms and
improve sleep quality and hence behavior and indicates the actigraphy as a choice
tool to characterize several parameters of the activity/rest rhythm of ASD
individuals.
PMID- 28426393
TI - A Systematic Literature Review of Experiences of Professional Care and Support
Among People Who Self-Harm.
AB - Self-harm is an increasing phenomenon among young people, with potentially fatal
outcomes. Patient's perceptions of treatment and support are poorly documented.
The aim was to synthesise the experiences of those who self-harm, with special
reference to professional care and support by family, friends, and the school
system. A systematic review of the literature was conducted. Following retrieval
of 1,623 abstracts, 14 studies were included in the final analysis, 11 of which
are reported here. Two quantitative studies as well as 1 mixed method study on
self-care could not be reported on here due to word limitations. Adult people who
self-harm described the importance of quality in the caring relationship and a
tailored care designed for each individual. There is a need for more studies into
adolescents who self-harm but of importance is the adolescents' need for support
from the adult world. A positive relationship between patient and healthcare
professional can be crucial in motivating continued treatment of people who self
harm. A major priority is radical improvement in the attitudes of healthcare
personnel.
PMID- 28426392
TI - Design and validation of a new method to detect and quantify residual host cell
DNA in human recombinant erythropoietin (rEPO).
AB - During the purification of human recombinant erythropoietin (rEPO) from host
cells, residual DNA may remain in final products. This contamination is a risk
factor for patients and may result in the inactivation of some tumor suppressor
genes or activation of oncogenes if its concentration is more than the standard
defined by WHO. Based on WHO's criteria, acceptable level of residual DNA in
biopharmaceuticals is less than 10-100 pg/dose. In this study, we have designed a
sensitive and specific quantitative real-time polymerase chain reaction (PCR)
assay for the detection of residual DNA in human rEPO products. All reported
sequences of CHO's GAPDH gene were retrieved from GenBank, and a multiple
alignment was performed using Mega 6 software to find conserved regions of the
gene. Primers and probe were designed by AlleleID7 software for the highly
conserved region. Quantitative real-time PCR showed an R2 value more than 0.99
and the efficiency equal to 101% indicating a highly accurate and efficiency of
the reaction, respectively. Based on the standard curve, the limit of detection
of the assay was determined to be 10 copies/uL (0.00967 fg/uL). In addition, the
inter- and intra-assay of the test were determined to be 1.14% and 0.65%,
respectively, which are in acceptable range according to the WHO's guidelines.
PMID- 28426394
TI - Attending the Wake of a Patient With a "Difficult" Family.
PMID- 28426395
TI - Compassion Fatigue and Compassion Satisfaction in Hospice Social Work.
AB - As part of the interprofessional team of hospice caregivers, social workers are
exposed to multiple stressors, both in their work with dying patients and their
families and in functioning as professionals within rapidly changing health care
organizations. Ongoing exposure to such stressors prompts concern about the
emotional and psychological effect working with people who are dying may have on
those who do it. Further, an understanding is needed regarding how hospice social
workers interpret the costs and benefits of their work and how they cope with the
dying and loss that pervade their everyday work lives. This descriptive, cross
sectional study explored the prevalence of compassion fatigue among hospice
social workers and considered compassion satisfaction as a means to mitigate
compassion fatigue. Fifty-five hospice social workers from 34 hospice
organizations in Michigan completed an online survey. Results suggested that
compassion fatigue is indeed a concern among hospice social workers. In addition,
compassion fatigue and compassion satisfaction were found to be negatively
correlated and suggested that compassion satisfaction may act as a protective
mechanism against compassion fatigue. These results may provide insight regarding
how best to mitigate this professional hazard in end-of-life social work.
PMID- 28426396
TI - Current Status of and Recommendations for Nutrition Education in Gastroenterology
Fellowship Training in Canada.
AB - PURPOSE: Knowledge and skill in the area of nutrition are a key competency for
the gastroenterologist. However, standards for nutrition education for
gastroenterology fellows in Canada do not exist, and gastroenterologists in
training and in practice do not feel confident in their knowledge or skill as it
relates to nutrition. This study was undertaken to identify the current status of
nutrition education in gastroenterology (GI) fellowship training programs in
Canada and to provide insight into the development of nutrition educational
goals, processes, and evaluation. METHODS: Using mixed methods, we did a survey
of current and recent graduates and program directors of GI fellowship programs
in Canada. We undertook a focus group with program directors and fellows to
corroborate findings of the survey and to identify strategies to advance
nutrition education, knowledge, and skill of trainees. RESULTS: In total, 89.3%
of the respondents perceived that the nutrition education was important for GI
training, and 82.1% of the respondents perceived nutrition care would be part of
their practice. However, only 50% of respondents had a formal rotation in their
program, and it was mandatory only 36% of the time. Of the respondents, 95% felt
that nutrition education should be standardized within GI fellowship training.
CONCLUSIONS: Significant gaps in nutrition education exist with GI fellowship
programs in Canada. The creation of standards for nutrition education would be
valued by training programs, and such a nutrition curriculum for GI fellowship
training in Canada is proposed.
PMID- 28426397
TI - A Successful Debrief Program for House Staff.
AB - Challenging end-of-life encounters can be stressful and may lead to burnout.
Monthly debriefing sessions are led by a physician and clinical social worker
(LCSW). Sessions focus on experiences and emotional reactions rather than case
details. Themes identified included; feeling unsupported after difficult deaths,
identifying with patients emotionally, and conceptualizing a "good" versus "bad"
death. Debriefing provides opportunities for residency physicians to reflect on
the affective side of their work and helps promote resiliency.
PMID- 28426398
TI - K-RAS and N-RAS mutations in testicular germ cell tumors.
AB - Testicular cancer is a relatively rare tumor type, accounting for approximately
1% of all cancers in men. However, among men aged between 15 and 40 years,
testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell
tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene
controls several cellular functions, including cell proliferation, apoptosis,
migration, and differentiation. Thus, RAS signaling is important for normal germ
cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over
20% of all cancers. RAS gene mutations have also been reported in TGCTs. We
investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT
patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases
were included in the study. K-RAS and N-RAS analyses were performed in our
molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In
total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5
non-seminoma cases (26%) [p = 0.55]. A K-RAS mutation was present in 4 pure
seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS
mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%)
[p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one
with seminoma tumor and the other with non-seminoma tumor. To date, no approved
targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS
and N-RAS mutations in these tumors may provide more treatment options,
especially in platinum-resistant tumors.
PMID- 28426400
TI - Morphological description of Cosmocerca sp. (Nematoda: Cosmocerdidae) from the
Mascarene grass frog Ptychadena cf. mascareniensis (Amphibia: Ptychadenidae). A
light and scanning electron microscopic studies.
AB - The Mascarene grass frog Ptychadena cf. mascareniensis is a species of frog with
a vast area of distribution in Africa. A total of 300 frog specimens were
collected from different localities at El-Giza province, Egypt; then dissected
and examined for the presence of parasitic infection. Only eighty six (28.66%)
specimens were found to be naturally infected with nematode parasite. Seasonally,
the prevalence of infection was reached its maximum value of 74.66% during summer
and minimum values of 26.66% (20/75), 13.33% (10/75) during spring and autumn,
respectively; while no records were observed during winter season. The morphology
of the recovered parasite was studied by using light and scanning electron
microscopy. The adult worm characterized by anterior extremity with small mouth
opening being surrounded by three lips provided with four sub-median cephalic
papillae and one pair of lateral amphids. Body measurements showed that male
worms were smaller than females measuring 1.22-2.43 (2.21 +/- 0.1) mm in length
and 0.21-0.34 (0.29 +/- 0.01) mm in width. Females measured 1.9-3.7 (2.8 +/- 0.1)
mm in length and 0.24-0.42 (0.38 +/- 0.01) mm in width. Comparing the present
parasite with other species of the same genus described previously, several
similarities were observed. However, peculiar new characteristics such as the
arrangement of plectanes and somatic papillae, the presence of gubernaculum, the
position of nerve ring, excretory pore, and vulval opening make it reasonable
belongs to the family Cosmocercidae and identified as Cosmocerca sp. In addition,
the present study was the first report for occurrence of cosmocercid species from
the Mascarene grass frog in Egypt.
PMID- 28426401
TI - A new species of the quill mite genus Chenophila Kethley, 1970 (Acariformes:
Syringophilidae) from the Marbled Teal Marmaronetta angustirostris (Menetries)
(Anseriformes: Anatidae) in Turkey.
AB - A new species of parasitic mite of the family Syringophilidae (Acariformes:
Cheyletoidea), Chenophila marmaronetta sp. nov. is described from the secondary
quill feathers of Marmaronetta angustirostris (Menetries) (Anseriformes:
Anatidae) from Turkey. This species differs from closely related Ch.
platyrhynchos Tymcio et al., 2013 by the presence of 9 chambers in each medial
branch of the peritremes (vs 5 chambers in Ch. platyrhynchos), length of the
stylophore 220-235 (vs 255-275), and lengths of setae vi, ve, d1 and d2 40-55, 65
70, 90-105 and 170, respectively (vs 65-85, 80-100, 130-170 and 85-150).
PMID- 28426402
TI - Molecular identification of Thelandros scleratus and Thelastoma icemi (Nematoda:
Oxyruida) using mitochondrial cox 1 sequences.
AB - Two species of parasitic nematodes collected from the intestine of Brook's House
Gecko, Hemidactylus brooki and American cockroach, Periplaneta americana L. The
parasites were identified as Thelandros scleratus and Thelastoma icemi by PCR
amplification method. Subsequently, sequence analysis of mt cox1 (504 and 540 bp)
for T. scleratus and T. icemi respectively revealed that these sequences showed
maximum similarity of 90% (in case of T. scleratus), 77% (in case of T. icemi),
to nematode sequences available on GenBank. To our knowledge, no cox1 sequence is
available for both the species of family Pharyngodonidae and Thelastomatidae.
This study represents the first mitochondrial DNA characterization of both
species.
PMID- 28426403
TI - PCR denaturing gradient gel electrophoresis as a useful method to identify of
intestinal bacteria flora in Haemaphysalis flava ticks.
AB - Ticks are blood-sucking ectoparasites of great medical and veterinary
significance that can transmit bacteria, protozoa, fungi and viruses, causing a
variety of human and animal diseases worldwide. In the present study, the
intestinal bacterial flora associated with Haemaphysalis flava ticks in different
developmental stages were analyzed using polymerase chain reaction (PCR) and
denaturing gradient gel electrophoresis (DGGE). Eleven distinct DGGE bands were
found using PCR-DGGE method. Sequences analyses indicated that they belonged to
Bacillus cereus, Candidatus rickettsia, Erwinia sp., Klebsiella pneumoniae,
Pectobacterium carotovorum, Pseudomonas aeruginosa, Rickettsia peacockii,
Rickettsia helvetica, Rickettsia slovaca, Staphylococcus simulans and Uncultured
bacterium clone. Our find that the K. pneumoniae and P. aeruginosa isolates were
presented in all H. flava ticks in different developmental stages. The present
results indicated that zoonotic pathogens are present in H. flava ticks in Henan
province, China. To our knowledge, this is the first report on intestinal
bacterial flora associated with H. flava ticks in China.
PMID- 28426404
TI - The ruby-crowned tanager Tachyphonus coronatus Vieillot, 1822 (Passeriformes:
Thraupidae) as a new host for Isospora ramphoceli Berto, Flausino, Luz, Ferreira,
Lopes, 2010 in Brazil.
AB - Despite 12 coccidian species had been recorded from passerines of the Thraupidae
family, none of them has been reported in the Parque Nacional do Itatiaia, in
Southeastern Brazil. This locality is a protected area with a high degree of
vulnerability, and is considered a "conservation island" of biodiversity. The aim
of the current work was describe Isospora ramphoceli Berto, Flausino, Luz,
Ferreira, Lopes, 2010 from ruby-crowned tanagers Tachyphonus coronatus Vieillot,
1822 in the Parque Nacional do Itatiaia. The oocysts of I. ramphoceli are
subspheroidal, 23.1 * 22.1 MUm, with smooth, bilayered wall. Micropyle, oocyst
residuum and polar granule are absent. Sporocysts are ellipsoidal or ovoidal,
16.2 * 10.8 MUm. Stieda body is knob-like and substieda body is large and
homogeneous. Sporocyst residuum is composed of many scattered granules.
Sporozoites are vermiform with a posterior refractile body and a nucleus. In
addition to new locality, this is the first description of I. ramphoceli from T.
coronatus.
PMID- 28426405
TI - Molecular evidence and additional morphological characters to distinguish
Ornithodoros brodyi and Ornithodoros yumatensis (Ixodida: Argasidae) in their
different developmental stages.
AB - Ornithodoros brodyi and Ornithodoros yumatensis are two species distributed in
the Americas and associated with bats and caves. Both species have similar
morphology, and the diagnostic traits of adults have not been detailed or
illustrated accurately. In this study, the independence of both species is
validated on the basis of molecular evidence (using partial sequences of 16S rDNA
gene), and the morphological differences between them (dentition of the hypostome
and traits of individual mammillae) are confirmed through light and scanning
electron microscopy. In addition to the above characteristics, we observed other
traits that may serve to differentiate both species: dorsal setae are short and
thick in O. yumatensis and are thin and moderate in size in O. brodyi. We also
observed a conspicuous hood in O. brodyi, which was absent in O. yumatensis.
Another characteristic observed is a line of setae, near the end of Tarsi II-IV,
which in O. brodyi is formed by less than five setae and in O. yumatensis by more
than five. The main morphological difference between larvae of the 2 species is
the number of ventral setae [9 (4 circumanal pairs) in O. brodyi and 8 (3
circumanal pairs) in O. yumatensis]. The genetic divergence in 16S rDNA sequences
between these two species ranges from 9.7 to 10.6%.
PMID- 28426406
TI - Infection of the lesser spotted dogfish with Proleptus obtusus Dujardin, 1845
(Nematoda: Spirurida) reflects ontogenetic feeding behaviour and seasonal
differences in prey availability.
AB - Proleptus obtusus Dujardin, 1845 is the most common parasite infecting the gut of
the lesser spotted dogfish (Scyliorhinus canicula, Linnaeus). This nematode is
trophically transmitted from an intermediate crustacean host to the definitive
elasmobranch host. Sexual and age-related differences in habitat occupancy and
feeding behaviour of the lesser spotted dogfish make this parasite-host dyad
ideal for testing which aspects of host biology influence parasite transmission.
Here, the relationship between P. obtusus burden and host condition, sex and age
were investigated in lesser spotted dogfish captured in the Northeast Atlantic.
Prevalence of P. obtusus was of 94.8% with a mean abundance of 23.3 worms per
host. Our results indicate that parasite burden is best explained by the
interaction between ontogenetic differences in foraging behaviour of the lesser
spotted dogfish and seasonal differences in prey availability.
PMID- 28426407
TI - Helminth (Cestoda, Nematoda) and coccidian (Apicomplexa: Eimeriidae) parasites of
the eastern small-footed myotis, Myotis leibii (Chiroptera: Vespertilionidae)
from Arkansas, with a description of a new species of Eimeria.
AB - During May and July 2016, 32 eastern small-footed myotis (Myotis leibii) were
collected from five counties of northwestern Arkansas and their faeces examined
for coccidian parasites. Four of 32 (13%) M. leibii harboured an eimerian that we
describe here as new. Oocysts of Eimeria sassei sp. n. were ovoidal to
ellipsoidal with a bi-layered wall and measured (length * width, L * W) 18.3 *
15.2 um, with an L/W ratio of 1.2. A micropyle and oocyst residuum were absent
but 1-2 polar granules were present. Sporocysts were ovoidal, 9.6 * 6.3 um, with
an L/W ratio of 1.5. A pronounced, button-like Stieda body was present but
substieda and parastieda bodies were absent. A sporocyst residuum was present as
distinct aligned or dispersed granules. One bat that we found dead was examined
for helminth parasites. It harbored the tapeworm, Vampirolepis sp. and a
nematode, Seuratum cancellatum. This is the first coccidian as well as the second
helminths reported from M. leibii. In addition, this is the seventh species of
coccidian parasite documented from Arkansas bats.
PMID- 28426408
TI - Isolation and molecular characterization of a Naegleria strain from a
recreational water fountain in Tenerife, Canary Islands, Spain.
AB - Free-Living Amoebae (FLA) are widely distributed protozoa in the environment and
have been isolated from many sources such as dust, soil and water. Among the
pathogenic genera included in this group Acanthamoeba spp., Naegleria fowleri and
Balamuthia mandrillaris have been reported to be causative agents of lethal
encephalitis, disseminated infections and keratitis. Naegleria fowleri is a
pathogenic FLA species which causes Primary Amoebic Meningoencephalitis (PAM). At
present there are not many available data on the distribution of Naegleria
species in Spain from environmental sources. Therefore, the aim of this study was
to evaluate the presence of this genus in recreational water sources in the
island of Tenerife, Canary Islands, Spain. In this study, ten samples collected
from recreational water fountains were checked for the presence of Naegleria spp.
using morphological and molecular identification tools. From the analysed
samples, only one sample (seawater fountain) was positive for Naegleria spp.
interestingly, not many reports of Naegleria spp. in seawater are available in
the literature and thus awareness should be raised among the environmental and
public health professionals.
PMID- 28426409
TI - A new species of Oochoristica (Cyclophyllidea: Linstowiidae) from non-native
Mediterranean geckos, Hemidactylus turcicus (Sauria: Gekkonidae), from Texas,
USA.
AB - A new species of cyclophyllidean tapeworm, Oochoristica harschi sp. nov. is
described from 2 of 18 (11%) non-native Mediterranean geckos (Hemidactylus
turcicus) collected in June 2016 from Tom Green County, Texas, USA The new
species has few characteristics in common with 17 species of Oochoristica
previously described from Nearctic reptiles. Of this group, O. harschi is most
similar to O. macallisteri Bursey and Goldberg, 1996 from the side-blotched
lizard, Uta stansburiana from Arizona and California, USA, in number of testes,
14-20 vs. 12-20. However, O. harschi has oval suckers and a long neck compared to
the circular suckers and absent neck in O. macallisteri. On comparison with other
species of Oochoristica, it was found O. chinensis Jensen, Schmidt and Kuntz,
1983 from the Sino-Japanese realm, O. iguanae Bursey and Goldberg, 1996 from the
Neotropical realm, and O. maccoyi Bursey and Goldberg, 1966 from the Panamanian
realm were most similar to the new species. However, O. harschi can be
differentiated by possessing a much longer neck and a shorter cirrus pouch. It
can be further differentiated from O. chinensis by possessing an ovoid vs. an
irregular vitellarium, from O. iguanae by having a smaller strobilus (65 vs. 110
mm) as well as an ovoid vs. a triangular vitellarium, and from O. maccoyi by
having significantly more proglottids (145 vs. 89) and a longer strobilus (65 vs.
20 mm). The new species is the fifth species of Oochoristica reported from non
native H. turcicus and the 18th species described from the Nearctic region.
PMID- 28426410
TI - Nematode parasites of the Chilean Flamingo, Phoenicopterus chilensis
(Phoenicopteridae) from Central Argentina, with a description of a new species of
Tetrameres (Tetrameridae).
AB - During the summer of 2013, several specimens of Phoenicopterus chilensis
(Phoenicopteridae) were found dead from unknown causes, in lakes from the
endorheic system "Encadenadas del Oeste", Buenos Aires Province, Argentina. Two
species of Nematoda were recovered from the proventriculus, one of them new for
science. The tetramerid Tetrameres (Tetrameres) salina n. sp. is mainly
characterized by having reduced pseudolabia, lips absent, six bifid teeth, males
with lateral alae, four rows of somatic spines and length ratio of spicules 1:12
32, and large females with eggs lacking polar filaments. The acuariid, Echinuria
skrjabinensis is described and illustrated, this finding represent the second
report of this nematode in Argentina and the first record in flamingos. This is
the first record of helminths parasitizing wild Chilean Flamingos, but it is not
possible to ensure that they accomplish their life cycle in this system of lakes,
because the migratory movements of the population of flamingos studied are
unknown.
PMID- 28426411
TI - Toxoplasma gondii in backyard pigs: seroepidemiology and mouse bioassay.
AB - The aim of this study was to evaluate the occurrence of Toxoplasma gondii in
backyard pigs destined for human consumption in Pernambuco state, Brazil. Blood
and tissue samples (liver, heart, brain, lung and diaphragm) were collected from
224 pigs from legal slaughterhouses and tested for T. gondii infection.
Antibodies to T. gondii were found in the sera of 37.9% (85/224) by using the
immunofluorescence antibody test (cut-off - 1:64). Tissue samples from
seropositive pigs were bioassayed in mice. Tissue samples from seropositive pigs
and from mice of the bioassay were submitted to histopathology,
immunohistochemistry, polymerase chain reaction (PCR) and sequencing; 14.1% of
pig tissue samples and 27.7% of bioassayed mouse samples were positive for T.
gondii DNA, but all pig and mouse tissues were negative in histopathology
analysis and immunochemistry. By using a risk assessment questionnaire, there was
significant difference (p<0.001) in seroprevalence of 21.2% (reproducer) and 3.1%
(finishing pig). These data serve as indicative of the sanitary conditions and
risk of T. gondii infection for backyard pigs. Preventive measures must be
implemented by health services to avoid toxoplasmosis human cases due to
ingestion of pig meat.
PMID- 28426412
TI - Fatal aelurostrongylosis in a kitten in Serbia.
AB - This paper describes a case of aelurostrongylosis in a four-month old female
domestic cat (Felis catus) from South Banat, Serbia. The kitten that had died
suddenly without signs of illness was autopsied in the Veterinary Specialised
Institute "Pancevo". The macroscopic finding was typical of granulomatous
pneumonia and subsequently, histopathology revealed verminous pneumonia. Based on
the parasite morphology, it was confirmed that the lung lesions were caused by
Aelurostrongylus abstrusus. The present finding contributes to the knowledge of
the prevalence of this underestimated parasite in the Balkan Peninsula.
PMID- 28426413
TI - New record of Steinernema arenarium (Artyukhovsky) (Rhabditida: Steinernematidae)
from Ukraine and a note on its distribution.
AB - During a survey of the biodiversity of entomopathogenic nematodes in Ukraine, a
population of Steinernema arenarium, strain Ch, was recovered in the sensitive
Chornobyl Exclusion Zone. In the present work, this strain was morphologically
and molecularly characterised using light microscopy and the sequences of the ITS
and D2-D3 region of the 28S rDNA. In addition, we sequenced the ITS and D2-D3
regions of four populations of S. arenarium from a laboratory collection.
Phylogenetic analyses were performed and the phylogenetic structure and
geographic distribution of S. arenarium are discussed.
PMID- 28426414
TI - Amoebicidal activity of alpha-bisabolol, the main sesquiterpene in chamomile
(Matricaria recutita L.) essential oil against the trophozoite stage of
Acanthamoeba castellani Neff.
AB - Acanthamoeba genus includes opportunistic pathogens which are distributed
worldwide and are causative agents of a fatal encephalitis and severe keratitis
in humans and other animals. Until present there are not fully effective
therapeutic agents against this pathogen and thus the need to search for novel
anti-amoebic compounds is urgent. Recently, essential oils of aromatic and
medicinal plants have shown activity against Acanthamoeba strains. Therefore,
this study was aimed to evaluate the activity of main component of chamomile
essential oil (a sesquiterpene) namely alpha-bisabolol against the Acanthamoeba
castellani Neff strain. After evaluation of the activity and toxicity of this
molecule, IC50 values of 20.839 +/- 2.015 for treated amoebae as well as low
citotoxicty levels in a murine macrophage cell line was observed. Moreover, in
order to elucidate mechanism of action of this molecule, changes in chromatin
condensation levels, permeability of the plasmatic membrane, the mitochondrial
membrane potential and the ATP levels in the treated amoebic strains were
checked. The obtained results revealed that alpha-bisabolol was able to induce
apoptosis, increase the permeability of the plasmatic membrane and decrease both
mitochondrial and ATP levels in the treated amoebae. Therefore, and given the
obtained results, alpha-bisabolol could be used a future therapeutic agent
against Acanthamoeba infections.
PMID- 28426415
TI - Detection of Echinococcus multilocularis DNA in fruit, vegetable, and mushroom
samples collected in the non-endemic territory of the Pomerania province and
comparison of the results with data from rural areas of the neighbouring highly
endemic Warmia-Masuria province, Poland.
AB - Echinococcus multilocularis is a tapeworm that may cause alveolar echinococcosis
(AE), one of the most dangerous parasitic zoonoses. As in the case of some
foodborne diseases, unwashed fruits and vegetables contaminated with eggs of E.
multilocularis may serve as an important transmission route for this parasite.
The aim of this study was to investigate the presence of E. multilocularis DNA in
fruit, vegetables, and mushrooms in rural areas of the Pomerania province, Poland
(non-endemic territory). In total, 104 environmental fruit, vegetable, and
mushroom samples collected in forests, plantations, and kitchen gardens were
analysed using nested PCR based on the mitochondrial 12S rRNA gene. E.
multilocularis DNA was detected in 6.7 % of the samples tested, which indicated
that the environment of the Pomerania province is contaminated with this
parasite, creating a potential risk for humans. Therefore, fresh fruit,
vegetables, and mushrooms should be washed before consumption. Additionally, the
results showed that the level of contamination is significantly lower than in the
highly endemic Warmia-Masuria province. The differences in the occurrence of E.
multilocularis in the environment of these neighbouring provinces appears to be
connected with the general epidemiological situation of these two regions, but
further study is required for an exact explanation.
PMID- 28426416
TI - How does host ecology influence sampling effort in parasite diversity estimates?
A case study using Neotropical freshwater fishes.
AB - Accurately estimating biodiversity is fundamental to ecological understanding and
prediction. Helminthes are often neglected in biodiversity estimates and when
included are often underestimated. Here we examine how sampling effort affects
estimates of parasite diversity in an assemblage of freshwater fish from a
floodplain in Brazil. We also examine how ecological and behavioral factors
influence the sampling effort necessary to accurately estimate the parasite
diversity associated with a fish species. We use our dataset to suggest that host
species with wide geographic distribution (i.e., long migrations), gregarious
behavior (i.e., shoal), larger body size, higher population density, wide diet
breadth (i.e., omnivorous), and autochthonous origin, increase the effort
necessary to estimate the total diversity of parasites. However, estimating this
parasitic fauna has several restrictions and limitations, due to the highly
complex of the floodplain ecosystems, with non-linear and non-random responses.
PMID- 28426417
TI - Neuropathological lesions of clinical and sub clinical Coenurosis (Coenurus
cerebralis) in organized goat farms in India.
AB - Clinical and sub clinical cases of Coenurosis due to Coenurus cerebralis in goats
were documented based on clinical, post mortem examination, identification of
parasitic stages, gross and histopathological lesions in brain of animals died
due to abnormal neurological symptoms. The most prominent site of predilection of
coenuri cysts in brain was cerebral hemispheres and multiple cysts were found in
majority of the cases. Generalized congestion, thinning of brain parenchyma due
to pressure atrophy, gliosis, neuronal degeneration, protoscolices in brain
parenchyma and inflammatory cell reactions predominantly comprised of lymphocytes
and macrophages were prominent neuropathological lesions observed in brain. This
study had significant implications in understanding the neuropathological lesions
to suggest suitable prevention and control measures in organized goat farms in
India.
PMID- 28426418
TI - First report on molecular evidence of Tylodelphys cerebralis (Diplostomulum
cerebralis) Chakrabarti, 1968 (Digenea: Diplostomidae) from snakehead fish Channa
punctata.
AB - Freshwater snakehead fish, Channa punctata (Perciformes: Channidae) from Meerut
(U.P.), India were screened for infection with metacercaria from the eye
(vitreous humor) and brain (cranial cavity) and were analyzed by molecular
methods using PCR and sequencing of the complete internal transcribed spacers
(ITS1-5.8S-ITS2) of the ribosomal RNA gene. Recovered metacercariae from sites,
vitreous humor and cranial cavity were previously diagnosed as Diplostomulum
cerebralis Chakrabarti, 1968 on the basis of morphological characteristics. A
combination of molecular methods in this study depicts that this is a species of
genus Tylodelphys Diesing, 1850 which was misinterpreted as Diplostomulum. Hence,
in this study, we validated the status of T. cerebralis (=D. cerebralis) after 49
years from its original description. The present work might contribute to expand
our knowledge for identification, biodiversity and taxonomy of diplostomids in
Indian fishes.
PMID- 28426419
TI - Ecological implications of floods on the parasite communities of two freshwater
catfishes in a Neotropical floodplain.
AB - The parasite communities of two freshwater catfishes (Auchenipterus osteomystax
and Trachelyopterus galeatus) were analyzed during the dry and rainy seasons in a
Neotropical floodplain. The nature of river-floodplain systems places specific
demands on parasite community structure, due to changes in the host environment.
It was therefore hypothesized that flood conditions lead to an increase in the
richness and abundance of fish parasites in the rainy season at the mouth of
Aguapei River floodplain. The Auchenipterus osteomystax parasite community was
richer (11 vs. eight) in species than T. galeatus, although the latter exhibited
a greater parasite burden (F1,108 = 126.99, P<0.0001). During the rainy season
both host species demonstrated high levels of parasitism (least squared means +/-
SE = 1.69 +/- 0.05 vs. 1.34 +/- 0.05; F1,108 = 21.45, P<0.0001). Differences were
found in the composition of the parasite species and the proportion of parasites
for each host species and between each seasonal period. Flood conditions during
the rainy season caused a change in the composition and structure of the
parasitic communities. The results corroborate the hypothesis that floods are one
of the most significant influences on shaping the parasite communities of fish in
floodplains. Our greatest concern is the reduction these dynamics and effects
bring about on local biota and, consequently, in host-parasite interaction. We
would therefore like to take this opportunity to warn environmental agencies and
hydroelectric companies about the importance of the conservation of the diversity
of this location.
PMID- 28426420
TI - Disruption of egg production by triclabendazole-resistant Fasciola hepatica
following treatment with a commercial preparation of myrrh (Mirazid).
AB - An in vitro study has been carried out to monitor changes to the female
reproductive system in adult triclabendazole (TCBZ)-resistant Fasciola hepatica
following treatment with a commercial preparation of myrrh ("Mirazid"). Flukes
were immersed for 6 h and 24 h in myrrh extract at a concentration of 200 ug/ml,
then processed for histological and transmission electron microscope (TEM)
examination of the uterus, Mehlis' gland, ovary and vitellaria. Egg production
had become abnormal at 6 h post-treatment (pt), with the uterine lumen being
filled with free vitelline cells and masses of shell protein material; few eggs
were present. At 24 h pt, no eggs were present. Distinct changes to the ovary and
Mehlis' gland were only observed after 24 h incubation in Mirazid. The ovary
contained numbers of apoptotic oogonia and oocytes. In the Mehlis' gland, the S1
cells were disorganised and the processes from them were vacuolated, although the
disruption was not significant. More severe changes were observed in the
vitelline cells and follicles. After 6 h incubation in Mirazid, although the
gross organisation of the vitelline follicles appeared to be normal, nuclear
changes indicative of the early stages of apoptosis were observed in the stem
cells and shell protein production by the mature cells had decreased. At 24 h pt,
a distinct shift in cell population was evident, with the follicles containing
mainly mature cells and spaces were present between the cells. The shell globule
clusters in the mature cells were disorganised. In more severely-affected
follicles, cells were seen to be breaking down, with karyolytic nuclei and
disintegrating cytoplasm. Overall, the results have shown that exposure to
Mirazid treatment had a severe impact on egg production by TCBZ-resistant flukes,
an effect that was mediated by disruption of the vitelline cells and of the
mechanism co-ordinating egg formation in the ootype.
PMID- 28426421
TI - Redescription of Philometra margolisi Moravec, Vidal-Martinez et Aguirre-Macedo,
1995 (Nematoda: Philometridae), a gonad-infecting parasite of the red grouper
Epinephelus morio (Serranidae) in the Gulf of Mexico.
AB - The insufficiently known nematode species Philometra margolisi Moravec, Vidal
Martinez et Aguirre-Macedo, 1995 (Philometridae) is redescribed based on light
and scanning electron microscopical (SEM) examinations of specimens collected
from the gonad of the type host, the red grouper Epinephelus morio (Valenciennes)
(Serranidae, Perciformes), in the northern Gulf of Mexico off Florida, USA. Also,
new prevalence data for females of P. margolisi were derived from 188 fish, and a
subset of these (n = 38) were used to determine prevalence and intensity of male
nematodes. The male of this species was studied with SEM for the first time,
which revealed some new, taxonomically important morphological features. The male
posterior end had a V-shaped caudal mound, four pairs of minute adanal papillae,
a pair of large papillae located posterior to the cloacal aperture and a pair of
very small phasmids. The distal end of the gubernaculum is unique among all gonad
infecting species of Philometra parasitizing serranids in that its ventral
surface is flat, smooth, without the usual two longitudinal grooves; the dorsal
lamellate structures on the gubernaculum are also different in this species. In
contrast to data in the original species description, the body length of gravid
females of P. margolisi was 132-280 mm. Overall prevalence for male nematodes
(76.3%) was much higher than for females (15.4%), and female nematode prevalence
was higher in samples collected during host spawing season than out of season
(27.1% and 3.3%, respectively).
PMID- 28426422
TI - Morphological re-description of Electrotaenia malapteruri (Cestoda:
Proteocephalidae) and Dujardinnascaris malapteruri (Nematoda: Heterocheilidae)
infecting the Electric catfish Malapterurus electricus and heavy metal
accumulation in host and parasites in relation to water and sediment analysis in
Lake Manzala, North Delta, Egypt.
AB - Parasites are one of the most serious limiting factors in aquaculture. The
Electric catfish Malapterurus electricus was subjected to study the prevalence
and mean intensity of parasitic infections throughout the whole year of 2015.
Heavy metals accumulation in host fish and parasites were determined in relation
to water quality and sediments of two different sites of Lake Manzala (Manzala
and Bahr El-Baqar), Egypt. A total of 100 specimens of Electric catfish were
collected and examined for the presence of helminth parasites. Two parasite
species were recovered and morphologically identified. These were cestoda
Electrotaenia malapteruri and nematode Dujardinnascaris malapteruri. Heavy metal
analysis in water and sediments showed that measured heavy metals in Bahr El
Baqar were found in risky levels higher than permissible limits and Manzala site.
Sediments were found to contain a higher level of metals than water samples.
Heavy metals accumulation in recovered parasites and their host were also
determined and showed significantly higher concentrations in parasites compared
to their host tissues. According to bioconcentration factors, E. malapteruri
showed that highest accumulation rate for all recorded elements up to 302.
Essential elements like Cu and Fe were found in significantly higher
concentrations in D. malapteruri, whereas E. malapteruri accumulated elements Cd,
Pb, Ni, Mn, Zn and Ca to a significantly higher degree. Accordingly, the ratios
(C[D.malapteruri]/C[E. malapteruri]) for most essential elements were higher than
0.5. Therefore, fish cestodes can be regarded as useful bio-indicators more than
nematodes when evaluating the environmental pollution of aquatic ecosystems by
heavy metals.
PMID- 28426423
TI - The discovery of acanthocephalans parasitizing chaetognaths.
AB - A comprehensive literature review shows that 12 types of pathogens,
micropredators and parasites are reported to interact with chaetognaths, mostly
digenean trematodes, cestodes and nematodes larval stages. Through analysis of
78,152 chaetognaths from a monthly zooplankton time series (Jan 1996-Dec 1998)
collected in the Mexican Central Pacific twelve acanthocephalan larvae
parasitizing chaetognaths were discovered. This is the first record of an
acanthocephalan parasitizing chaetognaths, raising to 13 the types of symbionts
known to interact with them (excluding predators). Cystacanth larval specimens of
Corynosoma sp. (Polymorphidae) were observed parasitizing the head, trunk and
caudal cavities of three of the eight chaetognath species inhabiting this
tropical coastal region (Flaccisagitta enflata, Flaccisagitta hexaptera and
Zonosagitta bedoti). Because Corynosoma sp. parasitized chaetognaths during
different months and years (Jan-Feb 1996, Mar and Jul 1997, Jan, Jun, Aug-Sep
1998) and because the total length of these cystacanths varied between 165-480
um, suggesting growth inside the hosts, we conclude that chaetognaths are
intermediate hosts of Corynosoma sp. The twelve parasitized chaetognaths were
juveniles (without gonads) or immature adults (none in reproductively mature
stage IV); therefore Corynosoma may have a negative influence on host
reproduction. Marine crustaceans (amphipods, decapods, copepods, mysids and
euphausiids) and fishes are common intermediate or paratenic hosts of
acanthocephalans. Fish, sea birds and marine mammals are definitive hosts for
marine Corynosoma species. The present discovery implies that acanthocephalans
are transmitted trophically through different intermediate hosts (crustaceans,
chaetognaths and/or fish); thus chaetognaths can also be part of the marine
acanthocephalan life cycle.
PMID- 28426424
TI - cDNA library construction of two human Demodexspecies.
AB - The research of Demodex, a type of pathogen causing various dermatoses in animals
and human beings, is lacking at RNA level. This study aims at extracting RNA and
constructing cDNA library for Demodex. First, P. cuniculiand D. farinaewere mixed
to establish homogenization method for RNA extraction. Second, D. folliculorumand
D. breviswere collected and preserved in Trizol, which were mixed with D.
farinaerespectively to extract RNA. Finally, cDNA library was constructed and its
quality was assessed. The results indicated that for D. folliculorum& D. farinae,
the recombination rate of cDNA library was 90.67% and the library titer was 7.50
* 104 pfu/ml. 17 of the 59 positive clones were predicted to be of D.
folliculorum; For D. brevis& D. farinae, the recombination rate was 90.96% and
the library titer was 7.85 x104 pfu/ml. 40 of the 59 positive clones were
predicted to be of D. brevis. Further detection by specific primers demonstrated
that mtDNA cox1, cox3and ATP6 detected from cDNA libraries had 96.52%-99.73%
identities with the corresponding sequences in GenBank. In conclusion, the cDNA
libraries constructed for Demodexmixed with D. farinaewere successful and could
satisfy the requirements for functional genes detection.
PMID- 28426425
TI - The role of domestic dogs in the transmission of zoonotic helminthes in a rural
area of Mekong river basin.
AB - Dogs have been bred since ancient times for companionship, hunting, protection,
shepherding and other human activities. Some canine helminth parasites can cause
significant clinical diseases in humans as Opisthorchis viverrini causing
cholangiocarcinoma in Southeast Asian Countries. In this study, socio-cultural
questionnaire, canine parasitological analysis, necropsy, parasite molecular
confirmation and dog roaming data were evaluated in Savannakhet, Lao-PDR, a
typical Mekong Basin area. Dog owners comprised 48.8% of the studied population,
with 61.2% owning one dog, 25.1% 2 dogs, 8.5% 3 dogs and 1.8% owning more than 4
dogs. Data from GPS logger attached to dogs showed they walked from 1.4 to 13.3
km per day, covering an area of 3356.38m2 average, with a routine of accessing
water sources. Thirteen zoonotic helminth species were observed. Causative agents
of visceral and cutaneous larva migrans occurred in 44.1% and 70% of the samples
respectively. Spirometra erinaceieuropaei was detected in 44.1% of samples.
Importantly, O. viverrini was found in 8.8% of samples. Besides the known
importance of dogs in the transmission of Ancylostoma spp., Toxocara spp. and S.
erinaceieuropaei, the observed roaming pattern of dogs confirmed it as an
important host perpetuating O. viverrini in endemic areas; their routine access
to waterbodies may spread O. viverrini eggs in a favorable environment for the
fluke development, facilitating the infection of fishes, and consequently
infecting humans living in the same ecosystem. Therefore, parasitic NTDs control
programs in humans should be done in parallel with parasite control in animals,
especially dogs, in the Mekong River basin area.
PMID- 28426427
TI - Three new species of Pharygodonidae (Nematoda: Oxyuridea) in Laudakia tuberculata
(Squamata: Agamidae) from Dehradun, Uttarakhand, India.
AB - Parapharyngodon tuberculata sp. nov., Thelandros tuberculata sp. nov. and
Thelandros dehradunensis sp. nov. (Nematoda: Pharyngodonidae) from the large
intestine of a rock lizard, Laudakia tuberculata Gray, 1827), are described and
illustrated. Parapharyngodon tuberculata sp. nov. is the 8th Oriental species and
59th species assigned to the genus Parapharyngodon and differs from other species
of the genus by possessing 3 pairs of caudal papillae, an echinate cloacal lip,
112-115 um spicule length and postbulbar ovary. Thelandros tuberculata sp. nov.
is the 5th and Thelandros dehradunensis sp. nov. the 6th Oriental species,
respectively, and they are the 40th and 41st species assigned to the genus
Thelandros. They differ from other species of the genus in caudal papillae
arrangement, length of spicules, and structure of the anterior end of the
esophagus. We transfer Parapharyngodon arequipensis Calisaya and Cordova, 1997 to
Thelandros arequipensis (Calisaya and Cordova, 1997) comb. n. based upon the
presence of a terminal operculum in the egg and large, pendant, caudal papillae.
PMID- 28426426
TI - Pseudopecoelus mccauleyi n. sp. and Podocotyle sp. (Digenea: Opecoelidae) from
the deep waters off Oregon and British Columbia with an updated key to the
species of Pseudopecoelus von Wicklen, 1946 and checklist of parasites from
Lycodes cortezianus (Perciformes: Zoarcidae).
AB - Pseudopecoelus mccauleyi n. sp. (Opecoelidae: Opecoelinae) is described from the
intestine of the bigfin eelpout, Lycodes cortezianus (Gilbert, 1890)
(Perciformes: Zoarcidae), collected at 200-800 m depths in the Northeastern
Pacific Ocean off Oregon and Vancouver Island, British Columbia. The new species
is distinguished by possessing a unique combination of the following diagnostic
characters: vitelline fields that extend to the posterior margin of the ventral
sucker; a slender, tubular and sinuous seminal vesicle that extends some distance
into the hindbody; an unspecialized, protuberant ventral sucker; a genital pore
at pharynx level; lobed to deeply multilobed testes; a lobed ovary; and an egg
size of 68-80 MUm * 30-46 MUm. A single specimen of Podocotyle Dujardin, 1845
(Digenea: Plagioporinae) is also described from the intestine of an individual
Coryphaenoides sp. (Gadiformes: Macrouridae) collected at 2,800 m depth off
Oregon. A listing of parasites from the bigfin eelpout as well as observations of
parasite diversity within relevant hosts are offered, new host and locality
records are noted, and a brief discussion of Pseudopecoelus von Wicklen, 1946 in
the deep sea is presented taking note of the low level of host specificity
recorded (i.e. spp. of Pseudopecoelus are now known to parasitize deep-water fish
from at least 20 piscine families). A new dichotomous key to the 39 recognized
species of Pseudopecoelus is introduced.
PMID- 28426428
TI - Vascular calcification: the role of microRNAs.
AB - Vascular calcification represents the deposition of calcium phosphate salts in
the tunica media of the vascular wall. It occurs during aging but is accelerated
and pronounced in patients with diabetes mellitus, chronic kidney disease (CKD)
and established cardiovascular disease. Due to the loss of elasticity of the
vessel wall, vascular calcification might result in left ventricular hypertrophy
and compromise coronary perfusion. Accordingly, several studies showed that
vascular calcification is associated with increased risk for cardiovascular
morbidity and mortality. Accumulating data suggest that microRNAs (miRs) play an
important role in vascular calcification. A variety of miRs have been implicated
in the development of vascular calcification, whereas others appear to play a
protective role. Accordingly, miRs might represent promising targets for the
prevention of vascular calcification and its adverse cardiovascular sequelae.
However, given the complexity of regulation of this process and the multitude of
miRs involved, more research is needed to identify the optimal candidate miRs for
targeting.
PMID- 28426429
TI - A candidate liquid chromatography mass spectrometry reference method for the
quantification of the cardiac marker 1-32 B-type natriuretic peptide.
AB - BACKGROUND: B-type natriuretic peptide (BNP) is a 32 amino acid cardiac hormone
routinely measured by immunoassays to diagnose heart failure. While it is
reported that immunoassay results can vary up to 45%, no attempt of
standardization and/or harmonization through the development of certified
reference materials (CRMs) or reference measurement procedures (RMPs) has yet
been carried out. METHODS: B-type natriuretic peptide primary calibrator was
quantified traceably to the International System of Units (SI) by both amino acid
analysis and tryptic digestion. A method for the stabilization of BNP in plasma
followed by protein precipitation, solid phase extraction (SPE) and liquid
chromatography (LC) mass spectrometry (MS) was then developed and validated for
the quantification of BNP at clinically relevant concentrations (15-150 fmol/g).
RESULTS: The candidate reference method was applied to the quantification of BNP
in a number of samples from the UK NEQAS Cardiac Markers Scheme to demonstrate
its applicability to generate reference values and to preliminary evaluate the
commutability of a potential CRM. The results from the reference method were
consistently lower than the immunoassay results and discrepancy between the
immunoassays was observed confirming previous data. CONCLUSIONS: The application
of the liquid chromatography-mass spectrometry (LC-MS) method to the UK NEQAS
samples and the correlation of the results with the immunoassay results shows the
potential of the method to support external quality assessment schemes, to
improve understanding of the bias of the assays and to establish RMPs for BNP
measurements. Furthermore, the method has the potential to be multiplexed for
monitoring circulating truncated forms of BNP.
PMID- 28426430
TI - Great need for changes in higher education in Greece.
PMID- 28426431
TI - Automated detection of unstable hemoglobin variants by Sysmex XE-Series
analyzers.
PMID- 28426432
TI - Surface as a motion surrogate for gated re-scanned pencil beam proton therapy.
AB - This simulation study investigated the dosimetric effectiveness and treatment
efficiency of surface motion guided gating of pencil beam scanning (PBS) proton
therapy for liver tumour treatments. Dedicated 4D dose calculations were
performed for simulating gated treatments using 4DCT data for six patients
derived from 4DMRI (4DCT(MRI)). Surface motion as a surrogate for tumour motion
was extracted from the 4DMRI images and a linear internal-external correlation
model applied to derive amplitude-based gating windows (GWs) of 10 and 5 mm. 4D
treatments were simulated using gating and layered/volumetric rescanning (either
alone or combined) and four assumed system latencies (50/100/200/500 ms) for the
response time of the beam gating to the surrogate. Resulting 4D plans were
compared using D5-D95 and V95 in the CTV as the primary metrics, as well as dose
to the healthy liver and total treatment time. With no motion mitigation,
interplay effects deteriorate the dose homogeneity by more than 30% with respect
to the static reference plan, whereas with surface motion guided gating alone,
this could be reduced to 12/20% and 5/10% (mean/max over all cases) for 10 mm and
5 mm GWs, respectively. Furthermore, by combining *5 layered rescans with 5 mm
GW, plan homogeneities to within 1/5% of the static references could be achieved.
Dose inhomogeneities were however still pronounced for latencies ?200 ms but
limited when ?100 ms. ITV volumes could be decreased by 19/25% when 10/5 mm GW
was employed, leading to reductions in mean dose to the healthy liver tissue of
2.6/3.3%. Our results confirm the potential of combining gating and re-scanning
(re-gating) for mitigating large tumor motions, and the potential of surface
motion monitoring as a gating signal.
PMID- 28426433
TI - Specific heat and Hall effect of the ferromagnetic Kondo lattice UCu0.9Sb2.
AB - We have investigated the electrical resistivity rho, specific heat C p and Hall
coefficient R H on a single crystal of a ferromagnetic Kondo lattice UCu0.9Sb2.
The experimental [Formula: see text], C p (T) and [Formula: see text] data
evidence a bulk magnetic phase transition at [Formula: see text] K, and
additionally exhibit an unexpected bump located in the temperature range T C/10-T
C/3. UCu0.9Sb2 has an enhanced electronic specific heat coefficient [Formula: see
text] mJ molK-2, corresponding to Kondo temperature [Formula: see text] K. An
analysis of the Hall effect data for j//(a, b)-plane and H// c-axis reveals that
the low-temperature ordinary Hall coefficient R 0 is positive, suggesting that p
type electrical conductivity is dominant. The density of the carriers at 2 K is
about 0.6 holes f.u.-1, which may categorize the studied compound into class of
low carrier density compounds. Combined gamma and R 0 data divulge an effective
mass of charge carriers [Formula: see text] 27 m e . This finding together with
quite low Hall mobility [Formula: see text] cm2 Vs-1 and Kadowaki-Woods ratio
[Formula: see text] [Formula: see text] cm (mol K2 mJ-1)2, manifest the
development of heavy-fermion state in the ferromagnetic UCu0.9Sb2 compound at low
temperatures.
PMID- 28426434
TI - Neutron scattering by Dirac multipoles.
AB - Scattering by magnetic charge formed by Dirac multipoles that are magnetic and
polar is examined in the context of materials with properties that challenge
conventional concepts. An order parameter composed of Dirac quadrupoles has been
revealed in the pseudo-gap phase of ceramic, high-T c superconductors on the
basis of Kerr effect and magnetic neutron Bragg diffraction measurements.
Construction of Dirac quadrupoles that emerge from centrosymmetric sites used by
Cu ions in the ceramic superconductor Hg1201 is illustrated, together with
selection rules for excitations that will feature in neutron inelastic
scattering, and RIXS experiments. We report magnetic scattering amplitudes for
diffraction by polar multipoles that have universal value, because they are not
specific to ceramic superconductors. To illustrate this attribute, we consider
neutron Bragg diffraction from a magnetically ordered iridate (Sr2IrO4) and
discuss shortcomings in published interpretations of diffraction data.
PMID- 28426435
TI - Surface plasmon resonance in gold nanoparticles: a review.
AB - In the last two decades, plasmon resonance in gold nanoparticles (Au NPs) has
been the subject of intense research efforts. Plasmon physics is intriguing and
its precise modelling proved to be challenging. In fact, plasmons are highly
responsive to a multitude of factors, either intrinsic to the Au NPs or from the
environment, and recently the need emerged for the correction of standard
electromagnetic approaches with quantum effects. Applications related to plasmon
absorption and scattering in Au NPs are impressively numerous, ranging from
sensing to photothermal effects to cell imaging. Also, plasmon-enhanced phenomena
are highly interesting for multiple purposes, including, for instance, Raman
spectroscopy of nearby analytes, catalysis, or sunlight energy conversion. In
addition, plasmon excitation is involved in a series of advanced physical
processes such as non-linear optics, optical trapping, magneto-plasmonics, and
optical activity. Here, we provide the general overview of the field and the
background for appropriate modelling of the physical phenomena. Then, we report
on the current state of the art and most recent applications of plasmon resonance
in Au NPs.
PMID- 28426436
TI - Challenges in computational evaluation of redox and magnetic properties of Fe
based sulfate cathode materials of Li- and Na-ion batteries.
AB - Several Fe-based sulfates have been proposed recently as cathode materials
characterized by a high average operating voltage (i.e. Li2Fe(SO4)2 and
Na2Fe2(SO4)3) or low fabrication temperature (e.g. Na2Fe(SO4)2.2H2O)). In this
work, we apply three methods to evaluate the redox potentials and magnetic
properties of these materials: (1) local density functional theory (DFT) in
Perdew-Burke-Ernzerhof parametrization; (2) rotationally invariant DFT + U; and
(3) DFT + U with magnetic exchange, suggested herein. The U parameters used for
DFT + U calculations have been evaluated by using a linear response method
(this applies to DFT + U as well as DFT + U calculations with a magnetic
exchange term). Moreover, we have performed adjustments of U and, for the case of
magnetic exchange, J parameters, to find better agreement with experimental
measurements of redox and magnetic properties. We find that a self-consistent DFT
+ U/linear response approach yields quite overestimated redox potentials as
compared to experiment. On the other hand, we also show that DFT + U
calculations are not capable of providing a reasonably accurate description of
both redox and magnetic properties for the case of Li2Fe(SO4)2, even when
adjusted U parameters are employed. As a solution, we demonstrate that a DFT +
U methodology augmented by a magnetic exchange term potentially provides more
precise values for both the redox potentials and the magnetic moments of the Fe
ions in the studied materials. Thus our work shows that for a more accurate
description of redox and magnetic properties, further extensions of the DFT + U
method, such as inclusion of the contribution of magnetic exchange, should be
considered.
PMID- 28426438
TI - Perceptions and Attitudes of Romanian People Toward Autopsy Procedures According
to the Level of Knowledge.
AB - In the last decade, Romanian hospitals have been facing a decline in autopsy
rates. This has had a negative impact on medical education and the training of
young doctors. Quite a number of caregivers strongly oppose the carrying out of
autopsies on their deceased loved ones who have died in hospital. Hence, this
study was designed to evaluate how autopsies are perceived by an average person
and whether improved knowledge about autopsies would help reduce people's
reluctance toward them. The study involved 216 willing participants who had
either never had a loved one die in hospital or had never had the power to make a
decision about their dead loved ones' body. The method of data collection used
was a medical inquiry-based questionnaire. Two questionnaires were used, one
before and one after brief information regarding autopsy procedures. Only a small
percentage of subjects really knew the meaning of an autopsy. Initially, they
accepted that it was easier to consent to their own autopsy than to the autopsy
of a loved one. This difference in opinion reduced after they were informed about
autopsies. As for arguments against autopsies, the most frequent were integrity
of the body and religious reasons. It is extremely useful to ensure people have
proper information, in order to help them understand and appreciate the benefits
of postmortem examinations. Religious, social, and cultural arguments might be
put aside if proper information and new educational programs are put in place.
PMID- 28426437
TI - Supersonic transient magnetic resonance elastography for quantitative assessment
of tissue elasticity.
AB - Non-invasive, quantitative methods to assess the properties of biological tissues
are needed for many therapeutic and tissue engineering applications. Magnetic
resonance elastography (MRE) has historically relied on external vibration to
generate periodic shear waves. In order to focally assess a biomaterial or to
monitor the response to ablative therapy, the interrogation of a specific region
of interest by a focused beam is desirable and transient MRE (t-MRE) techniques
have previously been developed to accomplish this goal. Also, strategies
employing a series of discrete ultrasound pulses directed to increasing depths
along a single line-of-sight have been designed to generate a quasi-planar shear
wave. Such 'supersonic' excitations have been applied for ultrasound elasticity
measurements. The resulting shear wave is higher in amplitude than that generated
from a single excitation and the properties of the media are simply visualized
and quantified due to the quasi-planar wave geometry and the opportunity to
generate the wave at the site of interest. Here for the first time, we extend the
application of supersonic methods by developing a protocol for supersonic
transient magnetic resonance elastography (sst-MRE) using an MR-guided focused
ultrasound system capable of therapeutic ablation. We apply the new protocol to
quantify tissue elasticity in vitro using biologically-relevant inclusions and
tissue-mimicking phantoms, compare the results with elasticity maps acquired with
ultrasound shear wave elasticity imaging (US-SWEI), and validate both methods
with mechanical testing. We found that a modified time-of-flight (TOF) method
efficiently quantified shear modulus from sst-MRE data, and both the TOF and
local inversion methods result in similar maps based on US-SWEI. With a three
pulse excitation, the proposed sst-MRE protocol was capable of visualizing quasi
planar shear waves propagating away from the excitation location and detecting
differences in shear modulus of 1 kPa. The techniques demonstrated here have
potential application in real-time in vivo lesion detection and monitoring, with
particular significance for image-guided interventions.
PMID- 28426439
TI - High Mortality Among Patients With Opioid Use Disorder in a Large Healthcare
System.
AB - OBJECTIVES: Elevated mortality has been observed among individuals with opioid
use disorder (OUD) treated in addiction specialty clinics or programs.
Information about OUD patients in general healthcare settings is needed in light
of the current effort to integrate addiction services into primary healthcare
systems. This study examined mortality rates, causes of death, and associated
risk factors among patients with OUD in a large general healthcare system.
METHODS: Mortality data were linked with electronic health records of 2576 OUD
patients cared for in a large university health system from 2006 to 2014.
RESULTS: There were 465 deaths confirmed (18.1% of the study participants),
corresponding to a crude mortality rate of 48.6 per 1000 person-years and
standardized mortality ratio of 10.3 (95% confidence interval [CI] 9.4-11.3).
Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer
(16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV])
were the leading causes of death. HCV (hazard ratio [HR] 1.99, 95% CI 1.62-2.46)
and alcohol use disorder (HR 1.27, 95% CI 1.05-1.55) were 2 clinically important
indicators of overall mortality risk. Tobacco use disorder (adjusted HR [AHR]
2.58, 95% CI 1.60-4.17) was associated with increased risk of cardiovascular
death, HCV infection (AHR 2.55, 95% CI 1.52-4.26) with cancer mortality risk, and
HCV (AHR 1.92, 95% CI 1.03-3.60) and alcohol use disorder (AHR 5.44, 95% CI 2.95
10.05) with liver-related mortality risk. CONCLUSIONS: Patients with OUD in a
general healthcare system demonstrated alarmingly high morbidity and mortality,
which challenges healthcare systems to find innovative ways to identify and treat
patients with substance use disorder.
PMID- 28426441
TI - Diagnosis of corneal limbal stem cell deficiency.
AB - PURPOSE OF REVIEW: A state of limbal stem cell deficiency (LSCD) can be secondary
to a number of etiologies, resulting in either a reduction in the total number of
limbal stem cells or an abnormality in stem cell function. Initially, the
epithelium becomes irregular and hazy; however, this condition may progress to
persistent corneal epithelial defects, stromal scarring, ulceration, and even
perforation. Since LSCD secondary to a variety of etiologies may be reversible,
and various factors are prognostic of disease progression, timely diagnosis is
important. This review will describe current knowledge of diagnostic techniques
for LSCD and understanding of epithelial stem cell function. RECENT FINDINGS:
Conjunctivalization, regarded as the most reliable clinical finding
diagnostically, can be identified as late staining of epithelium with
fluorescein. While identifying loss of the palisades of Vogt by slit-lamp
examination, can provide a high suspicion of LSCD, but this is not diagnostic.
Impression cytology is a simple, noninvasive technique that aids in the diagnosis
of LSCD, but a negative result also cannot rule out the diagnosis. Recent
findings have also shown that imaging techniques including in-vivo confocal
microscope and optical coherent tomography can also aid in diagnosing LSCD;
however, several challenges remain before these techniques become standard
diagnostic methods in clinical practice. Meanwhile, determination of the absence
of limbal epithelial crypts and focal stromal projections using image
reconstruction techniques may assist in the diagnosis of LSCD. Furthermore,
histologic markers may help not only to improve sensitivity and specificity of
conventional techniques in diagnosis of LSCD, but also to identify human limbal
stem cells and determine their number and function in LSCD. SUMMARY: Efforts to
develop and improve techniques for diagnosing LSCD are ongoing. Increased
knowledge of limbal stem cells and components of their niches may not only help
in understanding the pathogenesis of LSCD but may improve its diagnosis, thereby
ameliorating the prognosis of patients with this devastating disease.
PMID- 28426440
TI - The Impact of Couple HIV Testing and Counseling on Consistent Condom Use Among
Pregnant Women and Their Male Partners: An Observational Study.
AB - BACKGROUND: In sub-Saharan Africa couple HIV testing and counseling (CHTC) has
been associated with substantial increases in safe sex, especially when at least
one partner is HIV infected. However, this relationship has not been
characterized in an Option B+ context. SETTING: The study was conducted at the
antenatal clinic at Bwaila District Hospital in Lilongwe, Malawi in 2016 under an
Option B+ program. METHODS: Ninety heterosexual couples with an HIV-infected
pregnant woman (female-positive couples) and 47 couples with an HIV-uninfected
pregnant woman (female-negative couples) were enrolled in an observational study.
Each couple member was assessed immediately before and 1 month after CHTC for
safe sex (abstinence or consistent condom use in the last month). Generalized
estimating equations were used to model change in safe sex before and after CHTC
and to compare safe sex between female-positive and female-negative couples.
RESULTS: Mean age was 26 years among women and 32 years among men. Before CHTC,
safe sex was comparable among female-positive couples (8%) and female-negative
couples (2%) [risk ratio (RR): 3.7, 95% confidence interval (CI): 0.5 to 29.8].
One month after CHTC, safe sex was higher among female-positive couples (75%)
than among female-negative couples (3%) (RR: 30.0, 95% CI: 4.3 to 207.7). Safe
sex increased substantially after CTHC for female-positive couples (RR 9.6, 95%
CI: 4.6 to 20.0), but not for female-negative couples (RR: 1.2, 95% CI: 0.1 to
18.7). CONCLUSIONS: Engaging pregnant couples in CHTC can have prevention
benefits for couples with an HIV-infected pregnant woman, but additional
prevention approaches may be needed for couples with an HIV-uninfected pregnant
woman.
PMID- 28426442
TI - Amniotic membrane use for management of corneal limbal stem cell deficiency.
AB - PURPOSE OF REVIEW: The current article reviews the most recent surgical
techniques for management of corneal limbal stem cell deficiency (LSCD) using
amniotic membrane tissue. RECENT FINDINGS: Early successes with amniotic membrane
transplantation (AMT) for the treatment of ocular surface disorders have
encouraged clinicians to investigate new applications. The use of AMT as a
temporary patch in emergency cases in which LSCD may develop has considerably
improved the prognosis of these patients. Amniotic membrane does not have stem
cells of its own, but it supports regeneration of limbal epithelial stem cells
(LESCs). Similarly, the combination of AMT with classic surgical techniques has
enhanced the surgical success rates in most case series. Furthermore, based on
its advantageous properties as a cell carrier, new applications to support in
vivo and ex-vivo cell expansion have been reported recently. SUMMARY: LSCD
constitutes a general indication for AMT. Based on the clinical scenario, AMT may
be performed alone to support regeneration of LESCs, in combination with other
surgical techniques, or even supporting the in-vivo or ex-vivo expansion of
LESCs.
PMID- 28426443
TI - Independency of the cardio-ankle vascular index from blood pressure at the time
of measurement.
PMID- 28426444
TI - Fracture Liaison Services.
AB - PURPOSE OF REVIEW: The purpose of this review is to report the evidence of
beneficial effects of Fracture Liaison Service (FLS) including data regarding
their impact on subsequent fracture, mortality risk and cost-effectiveness. This
review also discusses the limitations of these data and the challenges faced
during the implementation of FLS. RECENT FINDINGS: Recent studies showed the
beneficial impact of implementation of FLS on the prevention of subsequent
fracture risk, reduced mortality and cost-effectiveness. However, heterogeneity
of FLS models and small number of studies limited the conclusion about the impact
of FLS on secondary fracture prevention. SUMMARY: Patients with osteoporosis
related fractures are at higher risk of subsequent refractures. These subsequent
fractures are associated with increased morbidity and premature mortality.
However, there is a gap between evidence-based recommendations for postfracture
care and actual clinical practice. FLS care is recommended for the management of
the prevention of secondary fracture. FLS implementation reduces the risk of
subsequent fracture, but the level of evidence is low as the interpretation of
data is limited by the number of studies and their heterogeneity. FLS care
significantly reduces the postfracture mortality, especially in patients with hip
fractures. FLS implementation is cost-effective compared with usual care.
Additional studies (with large sample and long-term follow-up) are needed to
assess the impact of FLS care on subsequent fracture risk.
PMID- 28426445
TI - Small, dense LDL: an update.
AB - PURPOSE OF REVIEW: In this review, we summarize the latest findings on small,
dense LDL (sdLDL) atherogenic particles, including their associations with other
biomarkers. RECENT FINDINGS: Increased sdLDL levels have been reported not only
in different metabolic disorders such as diabetes, obesity and metabolic
syndrome, but also in patients with rheumatoid and psoriatic arthritis as well as
hypothyroidism. A wide range of lipid-lowering, as well as other drug classes,
including novel antidiabetic agents and nutraceuticals, exert favourable effects
on these atherogenic particles. The 'gold standard' methodology for the
assessment of sdLDL has not been established yet. However, the association
between sdLDL and several biomarkers could facilitate their assessment. SUMMARY:
Estimation of sdLDL in daily clinical practice may help with the identification
of patients at high cardiovascular risk and further contribute in directing
specific interventions to prevent and/or decrease such risk.
PMID- 28426446
TI - Providing anesthesia in resource-limited settings.
AB - PURPOSE OF REVIEW: The article reviews the reality of anesthetic resource
constraints in low and middle-income countries (LMICs). Understanding these
limitations is important to volunteers from high-income countries who desire to
teach or safely provide anesthesia services in these countries. RECENT FINDINGS:
Recently published information on the state of anesthetic resources in LMICs is
helping to guide humanitarian outreach efforts from high-income countries. The
importance of using context-appropriate anesthesia standards and equipment is now
emphasized. Global health experts are encouraging equal partnerships between
anesthesia health care providers working together from different countries. The
key roles that ketamine and regional anesthesia play in providing well tolerated
anesthesia for cesarean sections and other common procedures is increasingly
recognized. SUMMARY: Anesthesia can be safely given in LMICs with basic supplies
and equipment, if the anesthesia provider is trained and vigilant. Neuraxial and
regional anesthesia and the use of ketamine as a general anesthetic appear to be
the safest alternatives in low-resource countries. Environmentally appropriate
equipment should be encouraged and pulse oximeters should be in every
anesthetizing location. LMICs will continue to need support from outside sources
until capacity building has made more progress.
PMID- 28426447
TI - Measles Cases in Children Requiring Hospital Access in an Academic Pediatric
Hospital in Italy, 2008-2013.
AB - BACKGROUND: The Lazio region is one of the Italian regions where sustained
measles transmission continues to occur. We investigated measles cases reported
by the emergency department (ED) of the largest pediatric hospital in Italy,
located in Lazio. METHODS: We reviewed clinical records of all measles cases from
0 to 18 years of age evaluated in the ED in 2008-2013. We compared demographic
and clinical characteristics of patients admitted to the inpatient setting with
those of patients discharged home to assess possible determinants of hospital
admission. RESULTS: Of 248 patients with measles evaluated in the ED, 113 (45.6%)
were admitted as inpatients. The number of measles cases peaked in 2011 (N = 122;
49.2%), when epidemics were reported in Lazio. Median age was 2.7 years (range:
21 days to 17.9 years), and 31 patients (13%) had an underlying chronic illness.
The strongest independent predictor of hospitalization was having an underlying
chronic illness [adjusted odd ratio (OR): 9.87; 95% confidence interval: 3.13
31.13]. Other factors independently and significantly associated with higher risk
of hospitalization were taking medications at the time of ED visit, being younger
than 1 year of age and having altered liver enzyme values. Eighty-five percent of
children >15 months of age who were hospitalized were not vaccinated. One hundred
six hospitalized children (94%) had at least 1 measles complication; 1 child
required intensive care for respiratory insufficiency. CONCLUSIONS:
Hospitalizations of children with measles continue to occur in European areas
where elimination has not been achieved. Children with chronic diseases represent
a vulnerable population that is at higher risk of hospitalization.
PMID- 28426448
TI - Clinical and ethical challenges in heart transplantation from donation after
circulatory determined death donors.
AB - PURPOSE OF REVIEW: The aim of this study was to describe the development of a
clinical programme of heart transplantation from nonheart beating (or donation
after circulatory determined death, DCD) donors. DCD is an established practice
in abdominal and lung transplantation. The opportunity for sufferers of advanced
heart failure provided by DCD heart transplantation is described. RECENT
FINDINGS: Work shows that the arrested DCD heart is viable and has a 30-min
tolerance to anoxia at normal body temperature making transplantation possible.
SUMMARY: The demonstration of the possibility of DCD heart transplantation and
its early clinical success is described.
PMID- 28426449
TI - Temperature and oxygenation during organ preservation: friends or foes?
AB - PURPOSE OF REVIEW: The liberalization of donor selection criteria in organ
transplantation, with the increased use of suboptimal grafts, has stimulated
interest in ischemia-reperfusion injury prevention and graft reconditioning.
Organ preservation technologies are changing considerably, mostly through the
reintroduction of dynamic machine preservation. Here, we review the current
evidence on the role of temperature and oxygenation during dynamic machine
preservation. RECENT FINDINGS: A large but complex body of evidence exists and
comparative studies are few. Oxygenation seems to support an advantageous effect
in hypothermic machine preservation and is mandatory in normothermic machine
preservation, although in the latter, supraphysiological oxygen tensions should
be avoided. High-risk grafts, such as suboptimal organs, may optimally benefit
from oxygenated perfusion conditions that support metabolism and activate
mechanisms of repair such as subnormothermic machine preservation, controlled
oxygenated rewarming, and normothermic machine preservation. For lower risk
grafts, oxygenation during hypothermic machine preservation may sufficiently
reduce injuries and recharge the cellular energy to secure functional recovery
after transplantation. SUMMARY: The relationship between temperature and
oxygenation in organ preservation is more complex than physiological laws would
suggest. Rather than one default perfusion temperature/oxygenation standard,
perfusion protocols should be tailored for specific needs of grafts of different
quality.
PMID- 28426450
TI - IBD LIVE Series-Case 7: The Brain-Gut Connection and the Importance of Integrated
Care in IBD.
PMID- 28426451
TI - Quality of Care and Outcomes Among Hospitalized Inflammatory Bowel Disease
Patients: A Multicenter Retrospective Study.
AB - BACKGROUND: Half of patients with inflammatory bowel disease (IBD) require
hospitalization. We sought to characterize inpatient quality indicators of care
and outcomes during IBD-related hospitalizations at 4 major IBD referral centers
in Canada. METHODS: We conducted a multicenter retrospective cohort study of
patients with IBD admitted from 2011 to 2013 to tertiary centers in Toronto,
Montreal, Ottawa, and Vancouver. We assessed the following inpatient indicators
of care: pharmacological venous thromboembolism (VTE) prophylaxis, Clostridium
difficile testing, and medical rescue therapy for steroid-refractory ulcerative
colitis (UC). We also evaluated rates of VTE, C. difficile infection, and IBD
related surgery. RESULTS: There were 837 patients hospitalized for IBD (Crohn's
disease, 59%; UC, 41%). The proportion of patients with IBD who received VTE
prophylaxis and C. difficile testing were 77% and 82%, respectively, although
these indicators varied significantly by center and admitting specialty. Patients
admitted under surgeons were more likely than those admitted under
gastroenterologists to receive VTE prophylaxis (84% versus 74%, P = 0.016) but
less likely to be tested for C. difficile (41% versus 88%, P < 0.0001). The rate
of VTE was the same for those who did and did not receive VTE prophylaxis (2.2
per 1000 hospital-days). Among the 14 VTE events, 79% had received prophylaxis,
but only 36% within 24 hours of admission. Among steroid-refractory UC patients,
70% received rescue therapy within 7 days of steroid initiation. The proportion
of patients with UC and CD who required respective bowel surgery was 18% and 20%,
respectively. CONCLUSIONS: There are opportunities to optimize quality of care
among hospitalized patients with IBD.
PMID- 28426452
TI - Defining the Most Appropriate Delivery Mode in Women with Inflammatory Bowel
Disease: A Systematic Review.
AB - INTRODUCTION: High cesarean section (CS) rates are observed in patients with
inflammatory bowel disease (IBD), but limited data are available to support this
decision. We conducted a comprehensive review to evaluate the most appropriate
mode of delivery in women with IBD according to disease phenotype and activity,
as well as surgical history. MATERIALS AND METHODS: We searched MEDLINE (source
PubMed) and international conference abstracts, and included all studies that
evaluated digestive outcome after delivery in patients with IBD. RESULTS: A total
of 41 articles or abstracts were screened, and 18 studies were considered in this
review, with sample sizes ranging from 4 to 229 patients and follow-up ranging
from 2 months to 7.7 years. Pooled CS rates in patients without Perianal Crohn's
disease (PCD), healed PCD or active PCD, were 27%, 43%, and 46%, respectively.
Regarding the median rate of new PCD (3.0% [IQR, 1.5-11.5] versus 6.5% [0-19.7])
or PCD recurrence (13.5% [3.2-32.7] versus 45% [0-58]), no increase was observed
in patients with vaginal delivery compared to CS, but for patients with an active
disease, worsening of symptoms was noted in two-thirds of cases. Episiotomy,
perianal tears, and instrumental delivery did not influence the incidence of PCD.
In patients with ileal pouch anal anastomosis, uncomplicated vaginal delivery
seemed to moderately influence pouch function, with no significant difference in
terms of overall continence, daytime, or night-time stool frequency, or
incontinence. However, these parameters seemed negatively impacted by a
complicated vaginal delivery. CONCLUSIONS: New long-term data from well-designed
studies are needed, but our review suggests that systematic CS in patients
suffering from IBD should probably be limited to women at risk of perineal tears
and obstetric injuries, with an active PCD, or with ileal pouch anal anastomosis.
PMID- 28426453
TI - Indications for Mode of Delivery in Pregnant Women with Inflammatory Bowel
Disease.
AB - BACKGROUND: Reasons for the increased incidence of cesarean delivery among women
with inflammatory bowel disease remain unclear. We assessed cesarean delivery
incidence and factors influencing mode of delivery in women with inflammatory
bowel disease. METHODS: We performed a 10-year retrospective cohort study of
nulliparous women who delivered a singleton infant at our institution. We
compared the risk of each mode of delivery in women with Crohn's disease and
ulcerative colitis with women without inflammatory bowel disease. We assessed
mode of delivery indications for patients with inflammatory bowel disease and
whether cesarean deliveries were planned. RESULTS: The overall incidence of
cesarean delivery among women with Crohn's disease (24/59; 40.7%) was similar to
that among women without inflammatory bowel disease (7868/21,805; 36.1%) (risk
ratio 1.1 [95% confidence interval, 0.83, 1.5]; P = 0.46), but was increased in
the subgroups with active and inactive perianal disease (risk ratio 2.3; P <
0.01). Women with ulcerative colitis had a 1.8-fold increased relative risk of
cesarean delivery (41/65; 63.1%) (95% confidence interval, 1.5, 2.1; P < 0.01),
with highest incidence in patients with ileal pouch-anal anastomosis. Forty-nine
percent of ulcerative colitis and 66.7% of Crohn's disease cesarean deliveries
were unplanned, with only 1 unplanned delivery performed for active inflammatory
bowel disease. Most unplanned deliveries were for arrest of descent/dilation and
nonreassuring fetal heart tracings. Seventy-five percent of planned cesarean
deliveries were for inflammatory bowel disease-related indications. CONCLUSIONS:
Women with ulcerative colitis and perianal Crohn's disease have an increased
incidence of cesarean delivery. At least half of cesarean deliveries are
unplanned.
PMID- 28426454
TI - Delivery Mode in Pregnant Patients with IBD: Uncertainty Remains.
PMID- 28426455
TI - Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related
Cytokines.
AB - BACKGROUND: Digoxin, a cardiac glycoside used for the treatment of heart failure,
was reported to inhibit the retinoid-related orphan receptor gamma t (RORgammat)
and attenuate the severity of experimental autoimmune encephalomyelitis and
arthritis in mice. However, the effects of digoxin in a mice model of
inflammatory bowel disease have not been elucidated. METHODS: Colitis was induced
in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T
cells. Digoxin or a vehicle was injected into mice with colitis intraperitoneally
every other day and changes in body weight were evaluated. After 6 to 8 weeks,
the treated mice were killed and evaluated for histological score, T-cell subset,
and cytokine messenger RNA (mRNA) expression in the colonic tissue. RESULTS:
Wasting disease and histological damage were significantly attenuated in digoxin
treated mice with colitis compared with those in the vehicle-treated mice. In
addition, the mRNAs of Th17-related cytokines were downregulated, whereas those
of interleukin-10 were upregulated in the colonic mucosa of digoxin-treated mice.
However, unexpectedly, the mRNA expression level of tumor necrosis factor alpha
did not decrease in the colonic mucosa of digoxin-treated mice with colitis. This
observation suggests that digoxin may ameliorate colitis by a tumor necrosis
factor alpha-independent pathway. CONCLUSIONS: This study has shown for the first
time that treatment with digoxin can ameliorate murine experimental colitis. This
finding suggests that the suppression of Th17 using reagents such as digoxin
could be effective in treating Crohn's disease refractory to anti-tumor necrosis
factor alpha therapy.
PMID- 28426456
TI - Expression and Localization of miR-21 and miR-126 in Mucosal Tissue from Patients
with Inflammatory Bowel Disease.
AB - BACKGROUND: microRNAs (miRNAs) are small noncoding RNAs that guide degradation of
mRNA and regulate protein expression. miRNA based diagnostic biomarkers for
ulcerative colitis (UC) and Crohn's disease (CD) are emerging but information
about the cellular localization of many miRNAs is limited and more detailed
histologic evaluation of miRNA expression patterns is needed to understand their
immunobiological function. METHODS: Formalin-fixed paraffin-embedded colon
biopsies from 10 patients with UC and 8 patients with CD together with 9 controls
were examined by RT-qPCR and quantitative in situ hybridization (ISH). The
cellular expression of miR-21 positive cells was further characterized using
immunohistochemical cellular markers. RESULTS: Increased levels of miR-21 and miR
126 were found in UC compared with controls and increased levels of miR-21 were
observed in UC compared with CD by both RT-qPCR and quantitative in situ
hybridization. miR-126 was localized to endothelial cells and miR-21 to cells in
the lamina propria. Multiplex immunohistochemical staining showed miR-21
expression in subsets of CD68 macrophages and CD3 T cells in UC, however, far the
majority of the miR-21 positive cells could not be categorized among CD68, CD3,
and CD19 cells. CONCLUSIONS: This study shows that miR-126 levels are increased
in UC and expressed in endothelial cells. miR-21 is expressed in subsets of
monocytes/macrophages and T cells and may work as a potential biomarker to
distinguish UC from CD. Quantitative in situ hybridization may be a powerful tool
for such analysis as it combines overall expression with validation of cellular
origin. Studies in larger cohorts may confirm this for clinical diagnostics.
PMID- 28426457
TI - Race Differences in Initial Presentation, Early Treatment, and 1-year Outcomes of
Pediatric Crohn's Disease: Results from the ImproveCareNow Network.
AB - BACKGROUND: Racially disparate care has been shown to contribute to suboptimal
health care outcomes for minorities. Using the ImproveCareNow network, we
investigated differences in management and outcomes of pediatric patients with
Crohn's disease at diagnosis and 1-year postdiagnosis. METHODS: ImproveCareNow is
a learning health network for pediatric inflammatory bowel disease. It contains
prospective, longitudinal data from outpatient encounters. This retrospective
study included all patients with Crohn's disease <=21 years, September 2006 to
October 2014, with the first recorded encounter <=90 days from date of diagnosis
and an encounter 1 year +/-60 days. We examined the effect of race on remission
rate and treatment at diagnosis and 1 year from diagnosis using t-tests, Wilcoxon
rank-sum tests, chi statistic, and Fisher's exact tests, where appropriate,
followed by univariate regression models. RESULTS: Nine hundred seventy-six
patients (Black = 118 (12%), White = 858 (88%), mean age = 13 years, 63% male)
from 39 sites were included. Black children had a higher percentage of Medicaid
insurance (44% versus 11%, P < 0.001). At diagnosis, Black children had more
active disease according to physician global assessment (P = 0.027), but not by
short Pediatric Crohn's Disease Activity Index (P = 0.67). Race differences in
treatment were not identified. Black children had lower hematocrit (34.8 versus
36.7, P < 0.001) and albumin levels (3.6 versus 3.9, P = 0.001). At 1 year, Black
children had more active disease according to physician global assessment (P =
0.016), but not by short Pediatric Crohn's Disease Activity Index (P = 0.06).
CONCLUSIONS: Black children with Crohn's disease may have more severe disease
than White children based on physician global assessment. Neither disease
phenotype differences at diagnosis nor treatment differences at 1-year follow-up
were identified.
PMID- 28426458
TI - Anti-TNFalpha Treatment After Surgical Resection for Crohn's Disease Is Effective
Despite Previous Pharmacodynamic Failure.
AB - BACKGROUND: The outcome of patients with Crohn's disease who failed anti-tumor
necrosis factor alpha (anti-TNFalpha) therapy despite adequate serum drug levels
(pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients
who underwent intestinal resection and were re-treated with the same anti
TNFalpha agent postoperatively. METHODS: Pediatric patients with Crohn's disease
who underwent intestinal resection and were treated with anti-TNFalpha agents
postoperatively were assessed retrospectively. Patients were stratified to those
with preoperative anti-TNFalpha pharmacodynamic failure and those with no
preoperative anti-TNFalpha treatment. RESULTS: A total of 53 children were
included, 18 with pharmacodynamic failure and 35 controls. Median age at
intestinal resection was 14.8 years with 23 (43%) girls. The median time from
intestinal resection to anti-TNFalpha initiation was 8 months (interquartile
range 4-14 months). At the time of postoperative anti-TNFalpha initiation there
were no differences in clinical, laboratory, and anthropometric measures between
groups. Similar proportions of patients from both groups were in clinical
remission on anti-TNFalpha treatment after 12 months and at the end of follow-up
(1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus
80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No
significant differences were observed at 14 weeks and 12 months of postoperative
anti-TNFalpha treatment including endoscopic remission rate and fecal
calprotectin. Both groups significantly improved all measures during
postoperative anti-TNFalpha treatment. CONCLUSIONS: Pediatric patients with
Crohn's disease who failed anti-TNFalpha therapy despite adequate drug levels and
underwent intestinal resection can be re-treated with the same agent for
postoperative recurrence with high success rate similar to that of anti-TNFalpha
naive patients.
PMID- 28426459
TI - The Association Between CMV Viremia or Endoscopic Features and Histopathological
Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis.
AB - BACKGROUND: Cytomegalovirus (CMV) infection has been shown to be related to
severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this
study was to evaluate the endoscopic and pathological characteristics of CMV
colitis in patients with UC and to assess the predictive value of the endoscopic
and pathological features of CMV colitis. METHODS: A total of 50 consecutive UC
patients with CMV infection who were admitted to Peking Union Medical College
Hospital from 2010 to 2015 were enrolled in this study. RESULTS: Twenty-five UC
patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff
value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq
polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%,
respectively. A higher proportion of endoscopic punched-out ulcers, irregular
ulcers, and cobblestone-like appearance were observed among the patients in the
CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%,
60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of
CMV inclusion bodies per high-power field was significantly higher in those with
punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of
pathological inflammation was observed in the CMV colitis group than in the
control group (68.0% versus 44.0%). CONCLUSIONS: Characteristic endoscopic
features with punch-out ulcers and high CMV viremia load may be useful for
predicting the presence of CMV colitis in histology. Punch-out ulcers were found
to be associated with a higher number of inclusion bodies on histology,
suggesting a role of targeted biopsy for endoscopist.
PMID- 28426460
TI - Is Mesalamine Effective for the Induction of Remission in Crohn's Disease?
PMID- 28426461
TI - Reply.
PMID- 28426462
TI - High-resolution esophageal manometry: interpretation in clinical practice.
AB - PURPOSE OF REVIEW: Esophageal high-resolution manometry (HRM) is the current
state-of-the-art diagnostic tool to evaluate esophageal motility patterns and, as
such, is widely adopted in clinical practice. This article will review the
interpretation of esophageal HRM in clinical practice. RECENT FINDINGS: HRM uses
a high-resolution catheter to transmit intraluminal pressure data that are
subsequently converted into dynamic esophageal pressure topography (EPT) plots.
Metric data from EPT plots are synthesized to yield an esophageal motility
diagnosis according to the Chicago Classification, a formal analytic scheme for
esophageal motility disorders, which is currently in version 3.0. The standard
HRM protocol consists of a baseline phase and a series of 10 wet swallows in the
supine or reclined position. In addition, data from swallows in the seated
position and provocative HRM maneuvers provide useful information about motility
properties. Combined high-resolution impedance technology is also clinically
available and enables concurrent assessment of bolus transit and postprandial
responses. Finally, there is ongoing interest to optimize the training and
competency assessment for interpretation of HRM in clinical practice. SUMMARY:
Esophageal HRM is a valuable and sophisticated clinical tool to evaluate
esophageal motility patterns. Emerging clinical applications of esophageal HRM
include combined impedance technology, provocative maneuvers, and postprandial
evaluation.
PMID- 28426463
TI - Treatments for achalasia in 2017: how to choose among them.
AB - PURPOSE OF REVIEW: To review recent advances in achalasia diagnostics and
therapeutics. RECENT FINDINGS: The cardinal feature of achalasia, impaired lower
esophageal sphincter (LES) relaxation, can occur in association with varied
patterns of esophageal contractility. The Chicago Classification distinguishes
among these as follows: without contractility (type I), with panesophageal
pressurization (type II), with premature (spastic) distal esophageal contractions
(type III), or even with preserved peristalsis [esophagogastric junction (EGJ)
outlet obstruction]. Physiological testing also reveals achalasia-like syndromes
that also benefit from achalasia therapies. Coincident with this has been the
development of peroral endoscopic myotomy (POEM), an endoscopic technique for
performing an esophageal myotomy. Hence, the option now exists to either
selectively ablate the LES (pneumatic dilation, laparoscopic Heller myotomy, or
POEM) or to ablate the sphincter and create a myotomy along some or the entire
adjacent smooth muscle esophagus (POEM). Each achalasia syndrome has unique
treatment considerations; type II achalasia responds well to all therapies,
whereas type III responds best to POEM. SUMMARY: Emerging data support the
concept that optimal management of achalasia is phenotype-specific, guided by
high-resolution manometry, and, in some instance, functional luminal imaging
probe studies. This opinion article reviews the varied characteristic and
treatment considerations of achalasia syndromes as currently understood.
PMID- 28426464
TI - Comparative effectiveness in urology: a state of the art review utilizing a
systematic approach.
AB - PURPOSE OF REVIEW: Comparative effectiveness research plays a vital role in
healthcare delivery by guiding evidence-based practices. We performed a state-of
the-art review of comparative effectiveness research in the urology literature
for 2016, utilizing a systematic approach. Seven high-impact papers are reviewed
in detail. RECENT FINDINGS: Across the breadth of urology, there were several
important studies in comparative effectiveness research, of which we will
highlight two randomized controlled trials and five observational trials:
radiotherapy, prostatectomy, and active monitoring have equivalent mortality
outcomes in patients with localized prostate cancer; the ideal modality of
patient education is yet to be determined, and written education has minimal
effect on patient perception of prostate specific antigen screening; robotic
prostatectomy is associated with higher perioperative complication rates on a
population basis; racial disparities exist in incontinence rates after treatment
for localized prostate cancer, but not in irritative, bowel, or sexual function;
androgen deprivation therapy is associated with higher fracture, peripheral
artery disease, and cardiac-related complications than bilateral orchiectomy;
robotic and open cystectomy offer comparable cancer-specific mortality and
perioperative outcomes; and bonuses for low-cost hospitals can inadvertently
reward low-quality hospitals. SUMMARY: There have been major advancements in
comparative effectiveness research in urology in 2016.
PMID- 28426465
TI - Neoadjuvant treatment: a novel standard?
AB - PURPOSE OF REVIEW: The aim of this study was to summarize developments in the
adjuvant/neoadjuvant chemotherapy of high-risk adult-type soft tissue sarcomas
(STS). RECENT FINDINGS: The role of adjuvant/neaodjuvant chemotherapy in these
patients is controversial, with a meta-analysis suggesting a 10% survival
benefit. Recently, a randomized controlled trial in high-risk STS of extremities
and trunk wall showed a 20% improvement in progression-free and overall survival
after three preoperative cycles of epirubicin along with ifosfamide compared with
a histology-tailored chemotherapy. This study has major strengths, including the
selected high-risk population and the full-dose chemotherapy regimen. However,
this was an interim analysis with a short follow-up in a trial originally planned
to test the superiority of a histology-driven chemotherapy. As to high-risk
patient selection, the new AJCC TNM staging system adds primary tumour site as a
stratifying factor, while available prognostic nomograms account for additional
criteria. SUMMARY: A recent trial strengthens perioperative chemotherapy as an
option for high-risk STS patients within a shared decision-making process. If the
final analysis of this trial confirms the currently observed progression-free and
overall survival benefits, perioperative chemotherapy may become a standard.
Also, new staging tools may refine our ability to select patients with a risk
high enough as to deserve chemotherapy.
PMID- 28426467
TI - Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted
Temperature Management: A Multicenter Study on 1,053 Patients.
AB - OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on
continuation or withdrawal of intensive care. Neuron-specific enolase is an
easily available, observer-independent prognostic biomarker. Recent studies have
yielded conflicting results on its prognostic value after targeted temperature
management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase
serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out
of-hospital cardiac arrest and outcome of patients from five hospitals in
Germany, Austria, and Italy. Patients were treated at 33 degrees C for 24 hours.
Cerebral Performance Category was evaluated upon ICU discharge. We performed case
reviews of good outcome patients with neuron-specific enolase greater than 90
MUg/L and poor outcome patients with neuron-specific enolase less than or equal
to 17 MUg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron
specific enolase serum concentration greater than 90 MUg/L predicted Cerebral
Performance Category 4-5 with a positive predictive value of 99%, false positive
rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific
enolase greater than 90 MUg/L and Cerebral Performance Category 1-2 had
confounders for neuron-specific enolase elevation. An neuron-specific enolase
serum concentration less than or equal to 17 MUg/L excluded Cerebral Performance
Category 4-5 with a negative predictive value of 92%. The majority of 14 patients
with neuron-specific enolase less than or equal to 17 MUg/L who died had a cause
of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity
for prediction of poor outcome were independent of age, sex, and initial rhythm
but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest
patients. CONCLUSION: High neuron-specific enolase serum concentrations reliably
predicted poor outcome at ICU discharge. Prediction accuracy differed and was
better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest
patients. Our "in-the-field" data indicate 90 MUg/L as a threshold associated
with almost no false positives at acceptable sensitivity. Confounders of neuron
specific enolase elevation should be actively considered: neuron-specific enolase
producing tumors, acute brain diseases, and hemolysis. We strongly recommend
routine hemolysis quantification. Neuron-specific enolase serum concentrations
less than or equal to 17 MUg/L argue against hypoxic-ischemic encephalopathy
incompatible with reawakening.
PMID- 28426468
TI - Indwelling tunneled pleural catheters for the management of hepatic hydrothorax.
AB - PURPOSE OF REVIEW: Hepatic hydrothorax is a complication of end-stage liver
disease that may have significant associated morbidity. Sodium restriction and
diuretic therapy are the mainstays of treatment, though up to a quarter of
patients will become refractory to this and will require a pleural drainage
procedure. Thoracentesis, transjugular intrahepatic portosystemic shunt, and
chemical pleurodesis all have variable success rates and associated complications
in the management of hepatic hydrothorax. Indwelling tunneled pleural catheters
(ITPC) have been successfully used to manage recurrent symptomatic malignant
pleural effusions, and there is growing interest regarding their use in the
management of hepatic hydrothorax. RECENT FINDINGS: Evidence regarding the use of
ITPC for nonmalignant pleural effusions has been limited to retrospective studies
and small feasibility trials. A recent meta-analysis regarding the use of IPTC
for nonmalignant pleural effusions demonstrated a rate of spontaneous pleurodesis
of 51%, whereas a small, prospective study demonstrated spontaneous pleurodesis
rates of 33% and an infection rate of 16.7% in 24 patients with ITPC placed for
hepatic hydrothorax in patients suitable for liver transplant evaluation.
SUMMARY: ITPC may be an acceptable treatment option for the management of hepatic
hydrothorax which are refractory to conventional medical management. Larger,
randomized controlled trials are needed to further evaluate the safety and
efficacy of these catheters for the management of nonmalignant pleural effusions.
PMID- 28426466
TI - Physician Variation in Time to Antimicrobial Treatment for Septic Patients
Presenting to the Emergency Department.
AB - OBJECTIVES: Delayed initiation of appropriate antimicrobials is linked to higher
sepsis mortality. We investigated interphysician variation in septic patients'
door-to-antimicrobial time. DESIGN: Retrospective cohort study. SETTING:
Emergency department of an academic medical center. SUBJECTS: Adult patients
treated with antimicrobials in the emergency department between 2009 and 2015 for
fluid-refractory severe sepsis or septic shock. Patients who were transferred,
received antimicrobials prior to emergency department arrival, or were treated by
an attending physician who cared for less than five study patients were excluded.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We employed multivariable
linear regression to evaluate the association between treating attending
physician and door-to-antimicrobial time after adjustment for illness severity
(Acute Physiology and Chronic Health Evaluation II score), patient age,
prehospital or arrival hypotension, admission from a long-term care facility,
mode of arrival, weekend or nighttime admission, source of infection, and trainee
involvement in care. Among 421 eligible patients, 74% received antimicrobials
within 3 hours of emergency department arrival. After covariate adjustment,
attending physicians' (n = 40) median door-to-antimicrobial times varied
significantly, ranging from 71 to 359 minutes (p = 0.002). The percentage of each
physician's patients whose antimicrobials began within 3 hours of emergency
department arrival ranged from 0% to 100%. Overall, 12% of variability in
antimicrobial timing was explained by the attending physician compared with 4%
attributable to illness severity as measured by the Acute Physiology and Chronic
Health Evaluation II score (p < 0.001). Some but not all physicians started
antimicrobials later for patients who were normotensive on presentation (p =
0.017) or who had a source of infection other than pneumonia (p = 0.006). The
adjusted odds of in-hospital mortality increased by 20% for each 1 hour increase
in door-to-antimicrobial time (p = 0.046). CONCLUSIONS: Among patients with
severe sepsis or septic shock receiving antimicrobials in the emergency
department, door-to-antimicrobial times varied five-fold among treating
physicians. Given the association between antimicrobial delay and mortality,
interventions to reduce physician variation in antimicrobial initiation are
likely indicated.
PMID- 28426469
TI - Prophylactic radiotherapy for procedure tract metastases in mesothelioma: a
review.
AB - PURPOSE OF REVIEW: Malignant pleural mesothelioma is an aggressive malignancy
with a very poor prognosis. The majority of patients require pleural procedures
for diagnostic or fluid management purposes. Damage to the pleura during these
procedures can lead to procedure tract metastases (PTMs), with increasing risk
from larger interventions. Prophylactic radiotherapy to these sites is a
controversial topic with conflicting results from trial data. In this review, we
summarize the recent evidence. RECENT FINDINGS: Four RCTs have been published on
this topic, with another in follow-up. The earliest, from a cohort of 40
patients, strongly advocated the use of prophylactic radiotherapy. More recent
trials, most notably the Surgical and large bore procedures in Malignant pleural
mesothelioma And Radiotherapy Trial (SMART) (which randomized over 200 patients)
did not demonstrate any benefit, especially when patient report symptoms and cost
effectiveness are considered. Certain subgroups demand further investigation,
such as those not receiving systematic chemotherapy or with surgical intervention
sites. The soon to be published Prophylactic Irradiation of Tracts (PIT) trial
may help to further clarify best practice. SUMMARY: Recent studies have shown
that prophylactic radiotherapy should not be routinely used to prevent PTMs in
mesothelioma. Instead patients should undergo careful clinical follow-up to
ensure PTMs are identified and treated promptly to minimize symptoms.
PMID- 28426470
TI - Identification and management of pleural effusions of multiple aetiologies.
AB - PURPOSE OF REVIEW: Historically, pleural effusions have been attributed to a
single cause. There is growing recognition that a substantial proportion of
pleural effusions may have more than one underlying cause. The purpose of this
review is to summarise recent findings regarding the diagnosis and treatment of
effusions secondary to more than one aetiology. RECENT FINDINGS: A recent
prospective study identified that 30% of pleural effusions had more than one
underlying aetiology. With a rising prevalence of cardiovascular and malignant
disease, the incidence of the complex pleural patient is increasing. The use of
biomarkers, including pro-B-type natriuretic peptide, have been suggested as a
way of identifying contributing disease process. SUMMARY: Understanding that
there are potentially concurrent causes to a pleural effusion is vital in
establishing the diagnoses of multiple underlying aetiologies. New diagnostic
pathways, with increasing use of biomarkers, will be required to identify the
complex pleural effusion. Further studies on whether the targeting of separate
aetiologies improves outcomes will help develop future management strategies.
PMID- 28426471
TI - Advances in the management of malignant pleural effusion.
AB - PURPOSE OF REVIEW: The current review describes the latest evidence in the
management of malignant pleural effusions (MPE). RECENT FINDINGS: Daily drainage
of indwelling pleural catheters achieved auto-pleurodesis at a higher rate
compared with every-other-day drainage [0.47 vs. 0.24; difference in proportion
of 0.23; 95% confidence interval (CI) 0.08-0.38; P = 0.003]. In patients with MPE
undergoing talc pleurodesis, a large multicenter randomized clinical trial found
that pain control with opiates vs. nonsteroidal anti-inflammatory drugs (NSAID)
group were not significantly different (mean visual analog scale of 23.8 vs. 22.1
mm, respectively, adjusted difference -1.5 mm; 95% CI 1.3-3.4; P = 0.40). NSAID
use was found to be noninferior to opiates with respect to the rate of
pleurodesis failure at 3-month follow-up (prespecified noninferiority margin 15%,
failure rates 20% opiates vs. 23% NSAIDS, respectively, difference -3%, 95% CI
10% to infinity; P = 0.004 for noninferiority). Talc remains the most effective
sclerosing agent based on multiple systematic reviews and meta-analyses. SUMMARY:
More prospective studies are needed to determine the optimal frequency of
indwelling pleural catheters drainage. NSAIDS can be used for pain control and do
not adversely impact the chance of successful pleurodesis.
PMID- 28426472
TI - Imaging in Patients with Crohn's Disease: Trends in Abdominal CT/MRI Utilization
and Radiation Exposure Considerations over a 10-Year Period.
AB - PURPOSE: To study the trends in utilization of computed tomography (CT) and
magnetic resonance imaging (MRI) in patients with Crohn's disease and to evaluate
changes in CT radiation exposure over a 10-year period. METHODS: In this
institutional review board-approved single-institution retrospective study, we
included patients who underwent CT and MRIs for evaluation of Crohn's disease
between 2006 and 2015. A total of 3196 CTs and 1924 MR scans were performed in
2156 patients (mean age: 34.8 +/- 17.71 yr; range: 3-91 yr) for initial diagnosis
or follow-up of Crohn's disease between 2006 and 2015. Trends in CT/MR
utilization was assessed by comparing the volume of CT/MRI studies performed each
year. The changes in CT radiation exposure over the study period were estimated
and compared. RESULTS: The annual combined CT/MR utilization demonstrated a 1.9
fold rise over the last decade (2006: n = 358, 2015: n = 681, P < 0.001, r =
0.96). It was predominantly because of a substantial growth (9.2-fold increase)
in the MR scan volume (2006: n = 37, 2015: n = 341, P < 0.001, r = 0.93), whereas
CT volume did not show significant change (2006: n = 321, 2015: n = 340, P =
0.6). Over this same period, there was a 59.4% reduction in mean radiation
exposure (2006: CT dose indexvol 16.9 +/- 7.1 mGy, 2015: CT dose indexvol 6.87 +/
4.62 mGy, P < 0.001). CONCLUSIONS: A 9-fold growth in annual MR scan volume
contributed to a nearly 2-fold rise in yearly cross-sectional imaging utilization
in Crohn's patients between 2006 and 2015. Rising trend in imaging utilization
paralleled a 60% reduction of CT radiation exposure.
PMID- 28426473
TI - Modifiable Risk Factors for Hospital Readmission Among Patients with Inflammatory
Bowel Disease in a Nationwide Database.
AB - BACKGROUND: Previous studies suggest that disease activity alone does not
reliably predict hospital readmission among patients with inflammatory bowel
diseases (IBDs). Using a national database, we aimed to further describe the
burden of readmissions for IBD and identify modifiable risk factors. METHODS: We
performed a retrospective cohort study using 2013 data from the Nationwide
Readmission Database (NRD). Using International Classification of Diseases, ninth
Revision, Clinical Modification (ICD-9-CM) codes, we identified adult patients
with discharge diagnoses of ulcerative colitis or Crohn's disease and ascertained
diagnoses of anxiety, depression, chronic pain, tobacco use, and other
comorbidities during index admission. Logistic regression was used to estimate
factors associated with hospital readmission. RESULTS: Among 52,498
hospitalizations of patients with IBD (63% Crohn's disease and 37% ulcerative
colitis), 12,407 (24%) were readmitted within 90 days of the index
hospitalization, resulting in roughly $576 million in excess charges. In
multivariable analysis of patients with Crohn's disease, anxiety (odds ratio [OR]
1.31, 95% confidence interval [CI], 1.21-1.43), depression (OR 1.27, 95% CI, 1.07
1.50), chronic pain (OR 1.31, 95% CI, 1.18-1.46), and tobacco abuse (OR 1.13, 95%
CI, 1.06-1.22) were associated with a significant increase in odds of
readmission. Among patients with ulcerative colitis, anxiety (OR 1.28, 95% CI,
1.14-1.45), depression (OR 1.35, 95% CI, 1.07-1.70), and chronic pain (OR 1.44,
95% CI, 1.21-1.73) were associated with a significant increase in odds of
readmission. CONCLUSIONS: Readmission occurs frequently in patients with IBD and
is costly. Anxiety, depression, and chronic pain may represent targets for
interventions to prevent 90-day hospital readmission in this population.
PMID- 28426475
TI - Reply to Letter to the Editor: "The HIBA Index for ALPPS, Preliminary Results to
Interpret With Caution".
PMID- 28426474
TI - Pouch-Related Symptoms and Quality of Life in Patients with Ileal Pouch-Anal
Anastomosis.
AB - BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA)
has become the standard surgical treatment for the majority of patients with
inflammatory bowel disease (IBD) who require colectomy. We evaluated the
prevalence of pouch-related symptoms among the Crohn's and Colitis Foundation of
America Partners cohort and the effect of pouch-related symptoms on Patient
Reported Outcome Measurement Information System measures. METHODS: We performed
analyses nested in the Crohn's and Colitis Foundation of America Partners cohort.
We used bivariate analyses to compare demographics and medication use among
patients with ulcerative colitis or indeterminate colitis and pouch-related
symptoms and those with IPAA without symptoms. We also compared Patient-Reported
Outcome Measurement Information System domains (measured in T-scores) and short
IBD questionnaire quality of life scales between symptomatic pouch patients (over
the past 6 mo) and those without symptoms. RESULTS: Among 243 patients reporting
a history of IPAA, 199 (82%) reported a history of pouch symptoms. Patients with
recent pouch symptoms demonstrated higher mean T-scores in pain interference
(53.0 versus 45.3; P < 0.001), depression (51.0 versus 46.4; P = 0.002), and
fatigue (56.3 versus 47.0; P < 0.001). Symptomatic pouch patients reported lower
mean scores in social role satisfaction (47.4 versus 54.6) and short IBD
questionnaire (4.8 versus 5.8) (both P < 0.001). These differences were all
clinically meaningful. CONCLUSIONS: In a large sample of patients with IBD,
nearly all patients with IPAA reported a history of pouch symptoms. Patients
experiencing symptoms within the 6 months before the survey assessment
demonstrated clinically meaningful decrements in patient-reported outcomes in
multiple domains of physical and psychosocial functioning.
PMID- 28426477
TI - Incidence of Adhesive Bowel Obstruction After Colon Cancer Surgery and its Risk
Factors: A Nationwide Claim Study.
AB - OBJECTIVE: To elucidate the incidence of adhesive postoperative bowel obstruction
(PBO) after colon cancer surgery and its risk factors using nationwide claim
data. BACKGROUND: PBO has a significant impact on quality of life and medical
costs after colectomy, though most of the literature consists of single
institution analyses. METHODS: Data from 24,645 patients who underwent regional
colectomy for colon cancer from 2010 to 2012 and had at least 3 years of follow
up were obtained from the Health Insurance Review and Assessment Service
database. Patients who required nasogastric tube insertion or bowel obstruction
surgery more than 30 days after index colectomy were defined as having PBO.
RESULTS: A total of 3083 (12.5%) patients experienced at least one PBO episode
within 3 years after surgery. Logistic regression analysis showed that
significant risk factors for PBO were elderly (odds ratio, OR = 1.13), male (OR =
1.27), open colectomy (OR = 1.99), and low-volume institution (OR = 1.17). Among
3083 PBO patients, 50.7% experienced their 1st PBO during the 1st year after the
index colectomy, and 7.8% experienced recurrence within 3 years after index
colectomy. The 3-year cumulative incidences of PBO according to risk factors of
elderly, male, open colectomy, and low-volume institution were 14.6%, 14.3%,
19.5%, and 15.1%, respectively. CONCLUSIONS: We report several independent risk
factors for PBO and its incidence after regional colectomy for colon cancer.
These results are informative for medical providers as patients who will or have
had the procedure and could be useful baseline data for further research on the
active prevention or treatment of PBO after colectomy.
PMID- 28426476
TI - Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase
2 Randomized Placebo-controlled Study (MIAS).
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric
injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a
controlled study. SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected
to definitively cure FI by regenerating damaged sphincter. Preclinical data and
results of open-label trials suggest that myoblast therapy may represent a
noninvasive treatment option. METHODS: We conducted a phase 2 randomized, double
blind, placebo-controlled study of intrasphincteric injections of AM in 24
patients. The study compared outcome after AM (n = 12) or placebo (n = 12)
injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months.
Patients in the placebo group were eligible to receive frozen AM after 1 year.
RESULTS: At 6 months, the median CCI score significantly decreased from baseline
in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups.
Hence, no significant difference was found between the 2 groups (primary
endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate
in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo
group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12
months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed
frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12
months. CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown
tolerance, safety, and clinical benefit at 12 months despite a transient placebo
effect at 6 months.
PMID- 28426478
TI - Advocating for a Sensible Firearm Injury Prevention Plan.
PMID- 28426480
TI - The HIBA Index for ALPPS, Preliminary Results to Interpret With Caution.
PMID- 28426479
TI - Long-term Impact of Bile Duct Injury on Morbidity, Mortality, Quality of Life,
and Work Related Limitations.
AB - OBJECTIVE: Assessment of long-term comprehensive outcome of multimodality
treatment of bile duct injury (BDI) in terms of morbidity, mortality, quality of
life (QoL), survival, and work related limitations. BACKGROUND: The impact of BDI
on work ability is scarcely investigated. METHODS: BDI patients referred to a
tertiary center after BDI were included (n = 800). QoL and work related
limitations (HLQ) were compared with 175 control patients after uncomplicated
laparoscopic cholecystectomy. RESULTS: The mean survival after BDI was 17.6 years
(95% confidence interval, CI, 17.2-18.0 years). BDI related mortality was 3.5%
(28/800). Corrected for sex, ASA classification, treatment and type of injury,
survival is worse in male patients (hazard ratio, HR 1.50, 95% CI 1.01-2.33) and
progressively worse with higher ASA classification (ASA2: 5.25 (2.94-9.37), ASA3:
18.1 (9.79-33.3). Patients treated surgically had a significantly better survival
(HR: 0.45 (95% CI: 0.25-0.80). BDI patients reported a significantly worse
physical QoL compared with the control group and worse disease specific QoL. Loss
of productivity of work was significantly higher among BDI patients. There also
was a significant hindrance in unpaid work. A higher number of bile duct injury
patients were receiving disability benefits after long-term follow-up (34.9% vs
19.6%, P = 0.004). CONCLUSIONS: Reconstructive surgery in BDI patients is
associated with improved survival. Although the clinical outcome of
multidisciplinary treatment of bile duct injury is good, it is associated with a
significant decrease in QoL, loss of productivity in both paid and unpaid work
and high rates of disability benefits use.
PMID- 28426481
TI - Response to: "Consideration of KRAS Mutation Status May Enhance the Prognostic
Impact of Indeterminate Extrahepatic Disease in the Lungs, as Identified by 18FDG
PET, in Patients With Colorectal Liver Metastases".
PMID- 28426482
TI - Legislative Strategies to Reduce the Toll of Firearm Injuries in America.
PMID- 28426483
TI - Beyond "Measure Twice": New Performance Standards in Surgery.
PMID- 28426484
TI - Connective Tissue Nevi: A Review of the Literature.
AB - Connective tissue nevi (CTN) are hamartomas of the dermis, with the 3 main
components being collagen, elastin, and proteoglycans. Each subtype can present
as a solitary lesion or multiple lesions. They could present as part of systemic
diseases or inherited disorders. This article provides a comprehensive literature
review of the different types of CTN, their clinical presentations, associations,
and treatment options. Treatment options for 56 lesions were reviewed. Fifty-two
percent of lesions were present in males, and the age range at the time of
presentation was wide (1.6-80 years). Management varied according to CTN
subtypes. Most lesions (14) received topical or intralesional treatment with
corticosteroids, followed by surgical removal of lesions (12), whereas the
remaining lesions were clinically monitored.
PMID- 28426485
TI - ALK Expression is a Rare Finding in Mycosis Fungoides.
AB - Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma.
Although indolent in its early stages, MF is more aggressive in advanced stages,
particularly if large cell transformation occurs. Histologically, transformed MF
is similar to primary cutaneous anaplastic large cell lymphoma (pcALCL) and nodal
ALCL (nALCL). MF had not been associated with immunohistochemical expression of
anaplastic lymphoma kinase (ALK) until we previously reported a case documenting
the presence of ALK by immunohistochemistry in a patient with stage IA MF and
concurrent nALCL. This is a unique finding due to the fact that ALK positivity is
usually found in nALCL. The goal of this study is to examine the extent to which
ALK may be expressed in the different morphologic lesions of MF. One hundred
three biopsies from 96 patients, including the patient from the original case,
with confirmed MF representing various lesion stages and subtypes, were tested
for ALK by immunohistochemical staining. Out of the 103 biopsies, only the
original index case of Stage IA MF with concurrent nALCL expressed ALK. From
these results, we conclude that ALK is not routinely present in MF in any lesion
stage or variant type. Routine staining of ALK is therefore of no additional
benefit for the workup of known early stage MF; however, its use may be
beneficial in the initial workup of unspecified large cell lymphomas of the skin.
PMID- 28426486
TI - Neutrophilic Figurate Erythema.
AB - Neutrophilic figurate erythema (NFE) has been rarely reported. This study aimed
to identify the clinical and pathological features of NFE. We retrospectively
reviewed the information from diagnostic cases from 2000 to 2013. The diagnosis
of NFE includes clinically annular rash, histopathologically predominant
neutrophilic perivascular and interstitial infiltrate in the dermis without
evidence of vasculitis, and exclusion of other known specific entities. Fifteen
cases of NFE were identified, including 11 women and 4 men. The age distribution
was 18-66 years (average 41). The major characteristic patterns in NFE were
blistering annular erythema (5/15 patients), purpuric annular erythema with
vesicles (4/15 patients), and multiple annular rash with central ring-shaped
scales (4/15 patients). There was no specific predicted location and no
association with a major systemic disease. Papillary dermal edema and mild-to
moderate leukocytoclasis in the upper dermis are the main histopathological
features. Ten of the 15 patients had recurrent episodes. Two patients who had
single episode were associated with drug reaction. Antineutrophil therapy was
required to control the symptoms in 3 patients. NFE has a similar clinical course
as erythema annulare centrifugum but has distinct features that can be recognized
clinically. The pathologists should be aware of the entity when making the
diagnosis of neutrophil-mediated inflammatory disorders. The treatment regimen
for neutrophilic dermatoses may be needed to manage the skin lesions.
PMID- 28426487
TI - Brief Report: HPV-17 Infection in Darier Disease With Acrokeratosis Verrucosis of
Hopf.
AB - The co-existence of Darier disease (DD) and acrokeratosis verruciformis of Hopf
(AKV) has been noted for decades and the relationship between the 2 entities
remains controversial. Although, it has been shown that both diseases are
associated with mutations in ATPA2 gene, it is yet to be determined if they are
the same disease, or separate but allelic, or interlinked in some other fashion.
Herein, the authors report the case of a 13-year-old girl presenting with shiny
flat-topped verruca plana-like papules, on the dorsal hands and feet and red
brown crusted papules on her forehead and along the sides of her neck.
Histological evaluation of a wart-like lesion shows features of AKV, a verruca
plana-like histopathology and focal acantholytic dyskeratosis. Forehead biopsy
also demonstrated focal acantholytic dyskeratosis supporting the diagnosis of DD.
Polymerase chain reaction for human papillomavirus (HPV) DNA detected HPV-17, a
human betapapillomavirus in the verruca plana-like papule. Cytoplasmic expression
of the L1 capsid expression was seen in areas of hypergranulosis. The presence of
productive betaPV infection in the setting of DD and AKV suggests a
susceptibility to HPV infection.
PMID- 28426488
TI - Melanocytes Containing Large Nuclei and Abundant Pale Cytoplasm in Melanocytic
Nevi.
PMID- 28426489
TI - A Large Congenital Blue Plaque With Papules and Nodules on the Lower Back.
PMID- 28426490
TI - Acute Necrotic Plaque in an Immunocompromised Host.
PMID- 28426491
TI - Treatment of Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia
Type 1: Some Clarity But Continued Controversy.
PMID- 28426493
TI - Clinical Features of Recurrent Acute Pancreatitis: Experience From a Single
Center.
PMID- 28426492
TI - Clinical Practice Guidelines for Pancreatic Cancer 2016 From the Japan Pancreas
Society: A Synopsis.
AB - OBJECTIVES: Clinical Practice Guidelines for Pancreatic Cancer based on Evidence
Based Medicine 2006 were first published by the Japan Pancreas Society, and they
were revised to Clinical Practice Guidelines for Pancreatic Cancer 2009 in July
2009 and were further revised to Clinical Practice Guidelines for Pancreatic
Cancer 2013 in October 2013. These guidelines were established according to
evidence-based medicine. In October 2016, the Clinical Practice Guidelines for
Pancreatic Cancer were newly revised in Japanese. METHODS: In the revised
version, we introduced the concepts of GRADE - grading recommendations
assessment, development, and evaluation approach for better understanding of the
current guidelines. RESULTS: The guidelines show algorithms for the diagnosis,
treatment, and chemotherapy of pancreatic cancer and address 7 subjects:
diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy,
stent therapy, and palliative medicine. They include 51 clinical questions and 76
statements. There are statements corresponding to clinical questions, evidence
levels, recommended strengths, and agreement rates. CONCLUSIONS: These guidelines
represent the most standard clinical and practical management at this time in
Japan. This is the English synopsis of the Clinical Practice Guidelines for
Pancreatic Cancer 2016 in Japanese, which aims to disseminate the Japanese
guidelines worldwide for the introduction of Japanese clinical management of
these diseases.
PMID- 28426494
TI - Reply to: Yang et al, Clinical Features of Recurrent Acute Pancreatitis:
Experience From a Single Center.
PMID- 28426495
TI - Biomarkers in the Differential Diagnosis of Pancreatic Diseases: Looking for a
Compass.
PMID- 28426496
TI - Successful Management of Pancreatic Kaposiform Hemangioendothelioma With
Sirolimus: Case Report and Literature Review.
PMID- 28426497
TI - The Cost of Surveying Intraductal Papillary Mucinous Neoplasms.
PMID- 28426498
TI - Pediatric Chronic Pancreatitis Due to Metabolic Disease: A Rare Etiology.
PMID- 28426499
TI - No Association Between Nonsteroidal Anti-inflammatory Drug Use and Pancreatic
Cancer Incidence and Survival.
PMID- 28426500
TI - Pancreatic Rheumatoid Nodule: Case Report and Review of the Literature.
PMID- 28426501
TI - Fluid Balance and Organ Failure in Acute Pancreatitis: Retrospective Cohort
Study.
PMID- 28426503
TI - Foreword.
PMID- 28426505
TI - Foreword.
PMID- 28426506
TI - Applications of Noninvasive Hemodynamic Monitoring in Obstetric Management.
AB - Clinicians managing obstetric patients are dependent on valid hemodynamic
measurements to guide care. Heart rate and noninvasive blood pressure guide most
current care. New hemodynamic monitors are being used to report research findings
and are being investigated by clinicians for their value to supplement standard
monitoring. These include arterial pulse contour analysis, Doppler velocimetry,
and bioimpedance among others. This chapter serves to present these new devices
with a critical review of their advantages and limitations, and most importantly
the validity of their measurements.
PMID- 28426507
TI - Peripartum Anesthetic Management of the Opioid-tolerant or Buprenorphine/Suboxone
dependent Patient.
AB - Opioid abuse and dependence continues to rise in both the general population and
pregnancy, with opioid overdose deaths having quadrupled in the last 15 years.
Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6%
documented maternal opiate use at time of birth. The management of the opioid
tolerant, buprenorphine-dependent or methadone-dependent patient in the
peripartum period is reviewed. Options for treatment of opioid dependence, acute
pain management, and perioperative multimodal analgesia are discussed. The
effects of maternal management on neonatal abstinence syndrome are also reviewed.
PMID- 28426509
TI - Log-Transformed Emg Amplitude-Power Output Relationship: Single-Leg Knee-Extensor
Versus Single-Leg Cycle Ergometry.
AB - Comparing and contrasting motor unit recruitment and activation for the same
muscles for multiple versus single-joint exercise may provide a better
understanding of neuromuscular fatigue. The purpose of this study, therefore, is
to compare the slope and y-intercept terms for the three superficial quadriceps
femoris (vastus lateralis, rectus femoris, and vastus medialis) muscles derived
from the log-transformed EMG amplitude-power output relationship between the
single-leg knee-extensor ergometry and the single-leg cycle ergometry. Ten
healthy college-aged men who engaged in regular physical activity visited the
laboratory on two occasions separated by seven days to perform either single-leg
cycle ergometry (CE) or single-leg knee-extensor ergometry (KE) in a randomized
order. For each visit, subjects performed incremental exercise until voluntary
fatigue. EMG electrodes were placed on the superficial quadriceps femoris
muscles. The slope and y-intercept terms, for each muscle, for the EMG amplitude
versus power output relationship was examined using the log-transformed model for
each subject's data. The results indicated no significant (p > 0.05) mean
differences for either slope or y-intercept terms between exercise modes and
across muscles. In addition, separate repeated measures ANOVAs were used to
determine mean differences for the slope and y-intercept values between the three
muscles. In addition, separate 2 [mode: CE or KE] * intensity [intensity: 30, 60,
and 90% of maximal workload] repeated measures ANOVAs were conducted for each
muscle. There was a significant (p < 0.05) mode * exercise intensity interaction
for each muscle. Follow-up testing indicated that in the most cases, the
normalized EMG amplitude was significantly higher for single-leg knee-extensor
ergometry than single-leg cycle ergometry. These results indicated that
incremental single-leg knee-extensor ergometry activates the superficial
quadriceps femoris muscles significantly greater than single-leg cycle ergometry.
PMID- 28426510
TI - Effect of External Loading on Force and Power Production During Plyometric Push
ups.
AB - Hinshaw, TJ, Stephenson, ML, Sha, Z, and Dai, B. Effect of external loading on
force and power production during plyometric push-ups. J Strength Cond Res 32(4):
1099-1108, 2018-One common exercise to train upper-body strength and power is the
push-up. Training at the loads that would produce the greatest power is an
effective way to increase peak power. The purpose of the current study was to
quantify the changes in peak force, peak power, and peak velocity among a
modified plyometric push-up and plyometric push-ups with or without external
loading in physically active young adults. Eighteen male and 17 female
participants completed 4 push-ups: (a) modified plyometric push-up on the knees,
(b) plyometric push-up without external loading, (c) plyometric push-up with an
external load of 5% of body weight, and (d) plyometric push-up with an external
load of 10% of body weight. Two force platforms were set up to collect vertical
ground reaction forces at the hands and feet. The modified plyometric push-up
demonstrated the lowest force, power, and velocity (5.4>= Cohen's dz >=1.2). Peak
force and force at peak velocity increased (3.8>= Cohen's dz >=0.3) and peak
velocity and velocity at peak power decreased (1.4>= Cohen's dz >=0.8) for the
push-up without external loading compared with the 2 push-ups with external
loading. No significant differences were observed for peak power among the push
ups with or without external loading (0.4>= Cohen's dz >=0.1). Although peak
power is similar with or without external loading, push-ups without external
loading may be more beneficial for a quick movement, and push-ups with external
loading may be more beneficial for a greater force production.
PMID- 28426511
TI - An Evaluation of Time-Trial-Based Predictions of V[Combining Dot Above]O2max and
Recommended Training Paces for Collegiate and Recreational Runners.
AB - Scudamore, EM, Barry, VW, and Coons, JM. An Evaluation of time-trial-based
predictions of V[Combining Dot Above]O2max and recommended training paces for
collegiate and recreational runners. J Strength Cond Res 32(4): 1137-1143, 2018
The purpose of the current study was to determine the accuracy of Jack Daniels'
VDOT Running Calculator for the prediction of V[Combining Dot Above]O2max, and
recommendations of interval and training paces (pIN and pTH) in samples of
National Collegiate Athletic Association Division 1 track athletes (ATH, n = 11)
and recreational runners (REC; n = 9). Predicted variable data were obtained
using results from indoor 5-km time-trials. Data from the VDOT Calculator were
compared with laboratory-tested V[Combining Dot Above]O2max, pace at V[Combining
Dot Above]O2max (V[Combining Dot Above]O2maxpace), and lactate threshold pace
(LTpace). Results indicated that VDOT underestimated V[Combining Dot Above]O2max
in ATH (t(10) = -6.00, p < 0.001, d = 1.75) and REC (t(8) = -8.96, p < 0.001, d =
3.44). Follow-up between-groups analysis indicated that the difference between
VDOT and V[Combining Dot Above]O2max was significantly greater in REC than in ATH
(p = 0.0031, d = 1.59). pIN was slower than V[Combining Dot Above]O2maxpace in
REC (t(8) = -4.26, p = 0.003, d = 1.76), but not different in ATH (t(10) = 0.52,
p = 0.614, d = 0.14). Conversely, pTH was faster than LTpace in ATH (t(8) =
4.17, p = 0.003, d = 1.49), but not different in REC (t(8) = 1.64, p = 0.139, d =
0.57). Practically, pTH can be confidently used for threshold training regardless
of the ability level. pIN also seemed to be accurate for ATH, but may be not be
optimal for improving V[Combining Dot Above]O2max in REC. Practitioners should
interpret VDOT with caution as it may underestimate V[Combining Dot Above]O2max.
PMID- 28426512
TI - Technology in S&C: Assessing Bodyweight Squat Technique with Wearable Sensors.
AB - Strength and conditioning (S&C) coaches offer expert guidance to help those they
work with achieve their personal fitness goals. However it is not always
practical to operate under the direct supervision of an S&C coach and
consequently individuals are often left training without expert oversight. Recent
developments in inertial measurement units (IMUs) and mobile computing platforms
have allowed for the possibility of unobtrusive motion tracking systems and the
provision of real-time individualised feedback regarding exercise performance.
These systems could enable S&C coaches to remotely monitor sessions and help
individuals record their workout performance. One aspect of such technologies is
the ability to assess exercise technique and detect common deviations from
acceptable exercise form. In this study we investigate this ability in the
context of a bodyweight (BW) squat exercise. IMUs were positioned on the lumbar
spine, thighs and shanks of 77 healthy participants. Participants completed
repetitions of BW squats with acceptable form and five common deviations from
acceptable BW squatting technique. Descriptive features were extracted from the
IMU signals for each BW squat repetition and these were used to train a technique
classifier. Acceptable or aberrant BW squat technique can be detected with 98%
accuracy, 96% sensitivity and 99% specificity when using features derived from
all 5 IMUs. A single IMU system can also distinguish between acceptable and
aberrant BW squat biomechanics with excellent accuracy, sensitivity and
specificity. Detecting exact deviations from acceptable BW squatting technique
can be achieved with 80% accuracy using a 5 IMU system and 72% accuracy when
using a single IMU positioned on the right shank. These results suggest IMU based
systems can distinguish between acceptable and aberrant BW squat technique with
excellent accuracy with a single IMU system. Identification of exact deviations
is also possible but multi-IMU systems outperform single IMU systems.
PMID- 28426513
TI - Evaluation of the Functional Movement Screen and a Novel Basketball Mobility Test
as an Injury Prediction Tool for Collegiate Basketball Players.
AB - Identifying injury risk and implementing preventive measures can assist in
reducing injury occurrence and may ultimately improve athletic performance.
Improper movement patterns often contribute to musculoskeletal (MSK) injuries.
The validity of the Functional Movement Screen (FMSTM) as an injury prediction
tool for athletes remains unclear. We designed the Basketball-Specific Mobility
Test (BMT) to represent the neuromuscular demands of basketball and identify
deficiencies that may be indicative of greater MSK injury risk while playing this
sport. The aim of this study was to examine the association of FMSTM and BMT
scores with injury occurrence in collegiate basketball players. We hypothesized
that the BMT would be a better predictor of injury risk than the FMSTM, and that
scores from both tests would have a higher association with severe MSK injuries
than minor, non-MSK injuries. One-hundred nineteen male and female collegiate
basketball players from four Upper Midwest universities were assessed pre- (PRE)
and post-season (POST) using the FMSTM and BMT. In-season injury records were
collected from the schools' athletic trainers and were classified by type and
severity. During the season, 56 of 119 players were injured, resulting in 96
total injuries. Injured athletes' PRE FMSTM scores demonstrated negligible
effects compared to uninjured athletes' PRE scores (d < 0.20), though some BMT
scores showed potentially meaningful effects (d > 0.20). While specificity of the
FMSTM and BMT to predict injury was relatively high (FMSTM 85.7-87.6; BMT 42.0
88.0), sensitivity (FMSTM 14.2-22.7; BMT 11.6-39.1), odds ratios (FMSTM 1.00
2.08; BMT 0.47-1.06), and injury prediction capacities (AUC; FMSTM 0.43-0.49; BMT
0.49-0.59) of the tests were low. Although the FMSTM and BMT may be suitable for
identifying MSK deficiencies, they do not accurately determine injury risk in
collegiate basketball players. Injury risk assessments may be improved by
targeting specific injury mechanisms and the conditions in which they occur.
PMID- 28426514
TI - Comparison of the Hang High-Pull and Loaded Jump Squat for the Development of
Vertical Jump and Isometric Force-Time Characteristics.
AB - Weightlifting movements have high skill demands and require expert coaching.
Loaded jumps have a comparably lower skill demand, but may be similarly effective
for improving explosive performance. The purpose of this study was to compare
vertical jump performance, isometric force, and rate of force development (RFD)
following a ten-week intervention employing the hang high-pull (hang-pull) or
trap-bar jump squat (jump-squat). Eighteen NCAA Division II swimmers (8 males, 10
females) with at least one year of resistance training experience volunteered to
participate. Testing included the squat jump (SJ), countermovement jump (CMJ) and
the isometric mid-thigh pull (IMTP). Vertical ground reaction forces were
analyzed to obtain jump height and relative peak power. Relative peak force, peak
RFD and relative force at five time bands were obtained from the IMTP. Subjects
were randomly assigned to either a hang-pull (n = 9) or jump-squat (n = 9)
training group and completed a ten-week, volume-equated, periodized training
program. While there was a significant main effect of training for both groups,
no statistically significant between-group differences were found (p >= 0.17) for
any of the dependent variables. However, medium effect sizes in favor of the jump
squat training group were seen in SJ height (d = 0.56) and SJ peak power (d =
0.69). Loaded jumps seem equally effective as weightlifting derivatives for
improving lower-body power in experienced athletes. Since loaded jumps require
less skill and less coaching expertise than weightlifting, loaded jumps should be
considered where coaching complex movements is difficult.
PMID- 28426515
TI - Can transcranial direct current stimulation improve muscle power in individuals
with advanced resistance training experience?
AB - The aim of this study was to investigate the effects of transcranial direct
current stimulation (tDCS) on countermovement jump performance (CMJ) in men with
advanced strength training experience. Ten healthy male subjects, with advanced
strength training and squatting exercise experience, were included. Participants
took part in an initial visit to the laboratory to complete anthropometric
measurements and CMJ kinematic test-retest reliability. Participants then
completed three experimental conditions, 48-72 hours apart, in a randomized,
double-blinded crossover design: anodal, cathodal and sham tDCS (2 mA for 20
minutes targeting the motor cortex bilaterally). Participants completed three CMJ
tests before and after each experimental condition, with one-minute recovery
interval between each test. The best CMJ in each moment was selected for
analysis. Two-way (condition by moment) repeated measures ANOVA's were performed
for CMJ height, flight time and muscular peak power. Effect sizes and
interindividual variability of tDCS responses were also analyzed. There was a
significant condition by moment interaction for all outcome measures, with a
large pre-post increase in CMJ height, flight time and muscular peak power in the
anodal condition. All the participants displayed CMJ performance improvements
after the anodal condition. There were no significant differences in both
cathodal and sham conditions. Anodal tDCS may be a valuable tool to enhance
muscle power related tasks performance, which is extremely relevant for sports
that require vertical jumping ability. Anodal tDCS may also be used to support
strength training, enhancing its effects on performance-oriented outcome
measures.
PMID- 28426516
TI - Physical Profiles of Female Academy Netball Players by Position.
AB - The purpose of this study was to evaluate the height, body mass and physical
characteristics of female academy netball players by position (centers, defenders
and shooters). Data were collected on 43 regional academy players during the
preseason period and comprised of height and body mass, and physical
characteristics (single-leg hop [SLH], squat jump [SJ], countermovement jump
[CMJ], 5- and 10-m sprint, 505 and cardiorespiratory fitness). Defenders and
shooters demonstrated significantly (p = < 0.05; d >= 1.1) greater body mass
compared to centers. Defenders demonstrated significantly (p = < 0.05; d = 1.6)
greater height compared to centers, however no significant differences were noted
between centers and shooters (p = 0.19; d = 0.7) and defenders and shooters (p =
0.70; d = 0.5). Centers performed better during the SLH left leg (p = 0.01; d =
1.0), SJ (p = 0.03; d = 1.1), CMJ (p = 0.01; d = 1.4), 5 m (p = 0.04; d >= -0.9)
and 10 m sprint (p = 0.01; d = -1.2), 505 left (p <= 0.03; d >= 1.0), 505 right
(p <= 0.03; d = 1.3), and cardiorespiratory fitness (p = 0.01; d >= 1.2),
compared to other positions. No other significant differences were observed.
These findings demonstrate that height, body mass and physical characteristics
differ between positions in female netball players, and provide normative data
for English academy netball players. Strength and conditioning coaches should
consider the specific demands on individual positions when training female
netball players.
PMID- 28426517
TI - Effects of Betaine Supplementation on Muscle Strength and Power: A Systematic
Review.
AB - Ismaeel, A. Effects of betaine supplementation on muscle strength and power: a
systematic review. J Strength Cond Res 31(8): 2338-2346, 2017-Betaine (BET) has
recently gotten much attention for its potential role as an ergogenic aid and has
become a common ingredient in peri-workout dietary supplements. The purpose of
this systematic review of the literature was to investigate the effects of BET
supplementation on muscular strength and power. A computerized literature search
of 3 databases (PubMed, MEDLINE, and Scopus) was performed. Included in the
review were randomized controlled trials that measured muscle strength, power, or
both measures in healthy participants. Quality was assessed using the PEDro
scale. Seven trials were identified, and quality assessment showed that all were
of "excellent quality." Only 2 of the studies reported increases in strength or
power after supplementation with BET. The remaining 5 studies showed no change in
any strength or power outcome measures with BET supplementation. This review
highlights the lack of evidence for a clear ergogenic effect of BET
supplementation on strength and power performance. However, because 2 studies did
identify increases of up to 24.61% on strength and power as a result of BET
supplementation, additional studies are necessary to evaluate its effectiveness.
PMID- 28426518
TI - Pathophysiologic insight into MesoAmerican nephropathy.
AB - PURPOSE OF REVIEW: Mesoamerican nephropathy (MeN) is an emerging
pathophysiological entity of Chronic kidney desease (CKD) not related to
traditional risk factors (diabetes and hypertension) that have caused thousands
of deaths in Central America, mainly in sugarcane workers. The focus of this
review is to discuss the risk factors and probable mechanisms involved in the
initiation and progression of this devastating disease. RECENT FINDINGS: Frequent
episodes of subclinical Acute kidney injury caused by repetitive heat stress,
dehydration, and strenuous work have been regarded as the main risk factors for
MeN. The combination of them chronically activates vasopressin, renin angiotensin
aldosterone system, and polyol-fructokinase pathway in the kidney. Also,
subclinical rhabdomyolysis compound the framework of the disease by exacerbating
systemic inflammation and inducing uricosuria. Exposure to nephrotoxins, high
fructose intake, and use of NSAIDs could also contribute to further accelerating
the progression of the disease. SUMMARY: The evidence supports the notion that
recurrent cycles of heat stress, dehydration, and strenuous work may cause CKD.
The chronic activation of such mechanisms likely occurs in other conditions of
reduced water intake and probably explains why the current management of CKD has
not been effective to revert or halt the progression to end-stage CKD.
PMID- 28426519
TI - Toward a universal antiretroviral regimen: special considerations of pregnancy
and breast feeding.
AB - PURPOSE OF REVIEW: As optimized antiretroviral therapy (ART) regimens are
prepared for introduction in low-income and middle-income countries (LMIC), we
consider the current evidence related to dosing, efficacy and safety during
pregnancy and breastfeeding of next-generation first-line and second-line ART
regimens proposed for imminent introduction in the global marketplace. RECENT
FINDINGS: Pregnancy pharmacokinetic considerations include potentially
insufficient efavirenz exposure if dosed at 400 mg/day, the need for twice daily
darunavir dosing and the paucity of data related to tenofovir alafenamide and
dolutegravir dosing, safety and efficacy. Increasingly evidence suggests an
association with adverse birth outcomes, particularly in women conceiving on ART,
and with varying risk by drug and drug combination. Clinical trials and studies
are in progress or planned that aim to determine dosing, safety and efficacy of
several new antiretrovirals (ARVs). SUMMARY: Having a universal, highly potent
and safe ART regimen for all individuals living with HIV in LMIC including
pregnant women is clearly the most beneficial strategy to keep mothers alive and
healthy and to prevent transmission of HIV to their children. It will have to be
determined whether the use of this next generation of optimized ARVs will also
optimize health outcomes of pregnant women and their children.
PMID- 28426520
TI - Nursing Practice, Research and Education in the West: The Best Is Yet to Come.
AB - PURPOSE: This paper celebrates the 60th anniversary of the Western Institute of
Nursing, the nursing organization representing 13 states in the Western United
States, and envisions a preferred future for nursing practice, research, and
education. BACKGROUND: Three landmark calls to action contribute to transforming
nursing and healthcare: the Patient Protection and Affordable Care Act of 2010;
the Institute of Medicine report Future of Nursing: Leading Change, Advancing
Health; and the report Advancing Healthcare Transformation: A New Era for
Academic Nursing. Challenges abound: U.S. healthcare remains expensive, with
poorer outcomes than other developed countries; costs of higher education are
high; our profession does not reflect the diversity of the population; and health
disparities persist. Pressing health issues, such as increases in chronic disease
and mental health conditions and substance abuse, coupled with aging of the
population, pose new priorities for nursing and healthcare. DISCUSSION: Changes
are needed in practice, research, and education. In practice, innovative,
cocreated, evidence-based models of care can open new roles for registered nurses
and advanced practice registered nurses who have knowledge, leadership, and team
skills to improve quality and address system change. In research, data can
provide a foundation for clinical practice and expand our knowledge base in
symptom science, wellness, self-management, and end-of-life/palliative care, as
well as behavioral health, to demonstrate the value of nursing care and reduce
health disparities. In education, personalized, integrative, and technology
enabled teaching and learning can lead to creative and critical thinking/decision
making, ethical and culturally inclusive foundations for practice, ensure team
and communication skills, quality and system improvements, and lifelong learning.
CONCLUSION: The role of the Western Institute of Nursing is more relevant than
ever as we collectively advance nursing, health, and healthcare through
education, clinical practice, and research.
PMID- 28426521
TI - A History of the Western Institute of Nursing and Its Communicating Nursing
Research Conferences.
AB - BACKGROUND: The Western Institute of Nursing (WIN) celebrated its 60th
anniversary and the 50th Annual Communicating Nursing Research Conference in
April 2017. PURPOSE: The purpose of this article is to provide a brief history of
the origin, development, and accomplishments of WIN and its Communicating Nursing
Research conferences. APPROACH: Historical documents and conference proceedings
were reviewed. SUMMARY: WIN was created in 1957 as the Western Council on Higher
Education for Nursing under the auspices of the Western Interstate Commission for
Higher Education. The bedrock and enduring value system of the organization is
the interrelated nature of nursing education, practice, and research. There was a
conviction that people in the Western region of the United States needed nursing
services of excellent quality and that nursing education must prepare nurses
capable of providing that care. Shared goals were to increase the science of
nursing through research and to produce nurses who could design, conduct, and
supervise research-all to the end of improving quality nursing care. These goals
were only achieved by collaboration and resource sharing among the Western region
states and organizations. Consistent with the goals, the first research
conferences were held between 1957 and 1962. Conference content focused on
seminars for faculty teaching research, on the design and conduct of research in
patient care settings, and on identification of priority areas for research. The
annual Communicating Nursing Research conferences began in 1968 and grew over the
years to a total 465 podium and poster presentations on a wide array of research
topics-and an attendance of 926-in 2016. CONCLUSION: As WIN and its Communicating
Nursing Research conferences face the next 50 years, the enduring values on which
the organization was created will stand in good stead as adaptability,
adjustments, and collaborative effort are applied to inevitable change for the
nursing profession. It is the Western way.
PMID- 28426522
TI - Patient Safety Culture Survey in Pediatric Complex Care Settings: A Factor
Analysis.
AB - OBJECTIVES: Children with complex medical needs are increasing in number and
demanding the services of pediatric long-term care facilities (pLTC), which
require a focus on patient safety culture (PSC). However, no tool to measure PSC
has been tested in this unique hybrid acute care-residential setting. The
objective of this study was to evaluate the psychometric properties of the
Nursing Home Survey on Patient Safety Culture tool slightly modified for use in
the pLTC setting. METHODS: Factor analyses were performed on data collected from
239 staff at 3 pLTC in 2012. Items were screened by principal axis factoring, and
the original structure was tested using confirmatory factor analysis. Exploratory
factor analysis was conducted to identify the best model fit for the pLTC data,
and factor reliability was assessed by Cronbach alpha. RESULTS: The extracted,
rotated factor solution suggested items in 4 (staffing, nonpunitive response to
mistakes, communication openness, and organizational learning) of the original 12
dimensions may not be a good fit for this population. Nevertheless, in the pLTC
setting, both the original and the modified factor solutions demonstrated similar
reliabilities to the published consistencies of the survey when tested in adult
nursing homes and the items factored nearly identically as theorized.
CONCLUSIONS: This study demonstrates that the Nursing Home Survey on Patient
Safety Culture with minimal modification may be an appropriate instrument to
measure PSC in pLTC settings. Additional psychometric testing is recommended to
further validate the use of this instrument in this setting, including examining
the relationship to safety outcomes. Increased use will yield data for
benchmarking purposes across these specialized settings to inform frontline
workers and organizational leaders of areas of strength and opportunity for
improvement.
PMID- 28426523
TI - Increasing HDL-C levels with medication: current perspectives.
AB - PURPOSE OF REVIEW: To date, observational studies have repeatedly demonstrated an
inverse association between HDL cholesterol (HDL-C) levels and cardiovascular
outcomes. Although the efficacy of established HDL-modifying treatment strategies
have been examined in multiple large-scale phase III trials, findings from these
experimental studies conflict with the hypothesis that HDL-C levels are
atheroprotective. In this review, we describe the trial evidence to date, and
attempt to place these results in the broader context of recent hypotheses for
the association between HDL-C levels and clinical outcomes. RECENT FINDINGS: Both
translational and genetic studies are in line with the hypothesis that HDL-C
levels do not hold causal importance for cardiovascular risk reduction. In
addition to its possible role as a biomarker for other atherogenic lipoproteins,
efforts should be made to elucidate HDLs' role in lipoprotein flux, which is
increasingly being linked to surrogate outcomes of importance to cardiovascular
epidemiology. In the future, it will be of great importance to link this measure
of HDL functionality to clinical endpoints. SUMMARY: Although trial evidence does
not support an atheroprotective role of overall HDL-C plasma levels, HDL
function/lipoprotein flux holds great promise for the development of novel
therapeutic approaches.
PMID- 28426524
TI - Beyond cascade screening: detection of familial hypercholesterolaemia at
childhood immunization and other strategies.
AB - PURPOSE OF REVIEW: Familial hypercholesterolaemia is a common genetic disorder
that accelerates premature coronary heart disease. Although effective treatments
are available, the majority of individuals remain undiagnosed. We review new
evidence for improving the detection of familial hypercholesterolaemia. RECENT
FINDINGS: Recent studies have demonstrated that universal screening of children
for familial hypercholesterolaemia may be highly effective at the time of
immunization if combined with reverse cascade testing of adult family members,
who have a more immediate risk of a coronary event. Alerts on laboratory reports
and the application of bioinformatics to electronic health records may also be
useful for identifying familial hypercholesterolaemia in community settings.
Effective detection, diagnosis, and codification of familial
hypercholesterolaemia are essential for the development of registries. SUMMARY:
Although the cost-effectiveness of screening programs for familial
hypercholesterolaemia in childhood remains to be established, combining universal
and reverse cascade screening, complemented by opportunistic identification of
individuals in high-risk settings, use of laboratory alerts, and screening of
electronic health records are likely to have a high yield in the detection of
familial hypercholesterolaemia in the community.
PMID- 28426525
TI - GSTM1 and GSTT1 Genes are Associated With DNA Damage of p53 Gene in Coke-oven
Workers.
AB - OBJECTIVES: This study investigated whether variations in GSTT1 and GSTM1 gene
are associated with the DNA damage level of p53 gene. METHODS: We quantified
urinary 1-hydroxypyrene using high-performance liquid chromatography, and
examined the DNA damage level of p53 gene by real-time quantitative PCR in 756
coke-oven workers. Multiplex PCR was used to detect the presence or absence of
genes. RESULTS: DNA damage levels of p53 gene in the high exposure group and
intermediate exposure group were significantly higher than that of p53 gene in
the low exposure group (P < 0.01). In coke-oven workers, the DNA damage levels of
subjects with non-null genotype in GSTT1 or GSTM1 gene were significantly higher
than that of those with the null genotype (P < 0.01). CONCLUSIONS: GSTT1 and
GSTM1 may modulate DNA damage levels of p53 gene when exposed to polycyclic
aromatic hydrocarbons.
PMID- 28426526
TI - Effect of Ambient Ozone Exposure Assessed by Individual Monitors on Nasal
Function and Exhaled NO Among School Children in the Area of Thessaloniki,
Greece.
AB - OBJECTIVES: The study of short-term effects of environmental ozone exposure on
nasal airflow, lung function, and airway inflammation. METHODS: Ninety one
children-47 underwent rhinomanometry-were included. The study was carried out
during the 2013 to 2014 academic year. Activity questionnaires and personal O3
samplers were distributed and 1 week later, respiratory measurements were
performed. Daily measurements of outdoor ozone were also considered. RESULTS: A
10 MUg/m increase in weekly personal ozone exposure concentrations was associated
with a non-statistically significant 12.7% decrease in nasal inspiratory airflow
(29.4% during the high ozone period). When the outdoor exposure of the same and
the previous day were taken into account the corresponding figures were 13.48%
and 43.58% (P = 0.02). CONCLUSIONS: There is an indication for increased risk of
nasal obstruction during exposure to high ozone.
PMID- 28426527
TI - US antibiotic stewardship and penicillin allergy.
AB - PURPOSE OF REVIEW: The purpose of this review is to improve otolaryngologists'
antibiotic stewardship by detailing current approaches to penicillin allergy.
RECENT FINDINGS: Although up to 15% of hospitalized patients in the United States
have a penicillin allergy recorded on their charts, fewer than 10% of these have
a true penicillin allergy. SUMMARY: Using a combination of a detailed allergy
history, skin testing and graded-dose administration, many patients whose charts
say 'penicillin-allergic' can safely be treated with penicillin and cross
reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves
money.
PMID- 28426528
TI - Comparative Analysis of Multicolor Flow Cytometry and Immunohistochemistry for
the Detection of Disseminated Tumor Cells.
AB - Disseminating cells of a primary solid tumor may represent the origin of
metastases and relapses. We aimed at comparing the diagnostic efficacy of
multicolor flow cytometry (MFC) and morphology/immunohistochemistry (IHC) in the
detection of disseminated tumor cells in the bone marrow (BM) and body fluids of
patients with solid tumors, and in pediatric neuroblastoma cases. We investigated
72 samples retrospecively from 50 patients by MFC. Morphology/IHC data were
available in 48 cases. In the first cohort, 36 samples derived from 34 patients
with various forms of suspected and proven solid tumors and in the second cohort,
36 samples of 16 children with suspected and proven neuroblastoma were analyzed
at diagnosis or during follow-up in a 4-color setting by MFC, and the results
were compared with those obtained by IHC. In the group of various solid tumors,
we found 91% concordance between IHC and MFC, and it was 65% in the neuroblastoma
group, and 77% overall. Detection of disseminated tumor cells was found to be
more effective by MFC in de novo neuroblastoma samples (100% vs. 86%). The
advantage of MFC was even more pronounced when minimal residual disease was
evaluated (efficacy, 92% vs. 68%). In contrast, efficacy of IHC was 100% in the
group of various solid tumors, whereas it was 91% for MFC. We conclude that MFC
and IHC are both essential tools for examining infiltration of BM and body fluids
by disseminating solid tumor cells. In the case of neuroblastoma, however,
minimal residual disease detection by MFC in a hypoplastic/aplastic BM
environment was more effective than IHC, as considerably more cells could be
analyzed.
PMID- 28426529
TI - Diagnostic Utility of Pax8, Pax2, and NGFR Immunohistochemical Expression in
Pediatric Renal Tumors.
AB - Pediatric renal tumors (PRT) with small round blue or spindle cell morphology can
be diagnostically challenging and only a limited number of immunohistochemical
markers have been documented to help in the diagnosis: paired box (Pax) 2 and
nerve growth factor receptor (NGFR) positivity have been demonstrated in Wilms
tumor (WT) and clear cell sarcoma of the kidney (CCSK), respectively. However,
the immunohistochemical expression of these markers in other PRT remains unknown.
This study investigated Pax8, Pax2, and NGFR immunophenotype in a large series of
PRT. Pax8 and Pax2 showed an identical staining pattern, and were expressed in
all (100%) WT while most CCSK were negative. All congenital mesoblastic
nephromas, metanephric stromal tumors, primitive neuroectodermal tumors,
desmoplastic small round blue cell tumors, most rhabdoid tumors, and synovial
sarcomas were negative for Pax8. NGFR was expressed in 96% of CCSK (diffuse
expression in 91%). Only a minority of WT stained for NGFR: 16% showed expression
in the blastemal and 25% in the mesenchymal components. NGFR expression was noted
in synovial sarcomas (67%, with diffuse expression seen in only 1 case, 8%),
rhabdoid tumors (19%), cellular congenital mesoblastic nephromas (13%) and
metanephric stromal tumors (12.5%). Primitive neuroectodermal tumors and
desmoplastic small round blue cell tumors were negative for NGFR. In conclusion,
Pax8/Pax2 and NGFR are sensitive markers for the diagnosis of WT and CCSK,
respectively. However, their specificity is limited by variable reactivity within
a subset of other renal neoplasms.
PMID- 28426530
TI - Intramuscular Local Anesthetic Infiltration at Closure for Postoperative
Analgesia in Lumbar Spine Surgery: A Systematic Review and Meta-Analysis.
AB - STUDY DESIGN: Systematic Review and Meta-Analysis OBJECTIVE.: To identify whether
intramuscular local anesthetic infiltration prior to wound closure was effective
in reducing postoperative pain and facilitating early discharge following lumbar
spine surgery. SUMMARY OF BACKGROUND DATA: Local anesthetic infiltration prior to
wound closure may form part of the multimodal strategy for postoperative
analgesia, facilitating early mobilization and discharge. Although there are a
number of small studies investigating its utility, a quantitative meta-analysis
of the data has never been performed. METHODS: This review was conducted
according the PRISMA statement and was registered with the PROSPERO database.
Only randomized controlled trials were eligible for inclusion. Key outcomes of
interest included time to first analgesic demand, total postoperative opiate
usage in the first 24 hours, visual analogue score (VAS) at 1, 12 and 24 hours
and postoperative length of stay. RESULTS: Eleven publications fulfilled the
inclusion criteria. A total of 438 patients were include; 212 in the control
group and 226 in the intervention group. Local anesthetic infiltration resulted
in a prolonged time to first analgesic demand (mean difference (MD) 65.88
minutes, 95% confidence interval (95% CI) 23.70 to 108.06, P.0.002) as well as a
significantly reduced postoperative opiate demand (M.D. -9.71 mg, 95% CI -15.07,
4.34, p = 0.0004). There was a small but statistically significant reduction in
postoperative visual analogue score (VAS) at 1 hour (M.D. -0.87 95%CI -1.55,
0.20, p = 0.01), but no significant reduction at 12 or 24 hours (p = 0.93 and
0.85 respectively). CONCLUSION: This systematic review and meta-analysis provides
evidence that postoperative intramuscular local anaesthetic infiltration reduces
postoperative analgesic requirements and the time to first analgesic demands for
patients undergoing lumbar spine surgery. Key research priorities include
optimization of the choice and strength of local anaesthetic agent and health
economic analyses to strengthen the case for routine use of postoperative local
anesthetics in lumbar spine surgery. LEVEL OF EVIDENCE: 1.
PMID- 28426531
TI - High-Fat Feeding Protects Mice From Ventilator-Induced Lung Injury, Via
Neutrophil-Independent Mechanisms.
AB - OBJECTIVE: Obesity has a complex impact on acute respiratory distress syndrome
patients, being associated with increased likelihood of developing the syndrome
but reduced likelihood of dying. We propose that such observations are
potentially explained by a model in which obesity influences the iatrogenic
injury that occurs subsequent to intensive care admission. This study therefore
investigated whether fat feeding protected mice from ventilator-induced lung
injury. DESIGN: In vivo study. SETTING: University research laboratory. SUBJECTS:
Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either
fed a high-fat diet for 12-14 weeks, or age-matched lean controls. INTERVENTIONS:
Anesthetized mice were ventilated with injurious high tidal volume ventilation
for periods up to 180 minutes. MEASUREMENTS AND MAIN RESULTS: Fat-fed mice showed
clear attenuation of ventilator-induced lung injury in terms of respiratory
mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation
within the lungs were not significantly attenuated nor were a host of circulating
or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix
metalloproteinase activity and levels of the matrix metalloproteinase cleavage
product soluble receptor for advanced glycation end products were significantly
attenuated in fat-fed mice. This was associated with reduced stretch-induced
CD147 expression on lung epithelial cells. CONCLUSIONS: Consumption of a high-fat
diet protects mice from ventilator-induced lung injury in a manner independent of
neutrophil recruitment, which we postulate instead arises through blunted up
regulation of CD147 expression and subsequent activation of intra-alveolar matrix
metalloproteinases. These findings may open avenues for therapeutic manipulation
in acute respiratory distress syndrome and could have implications for
understanding the pathogenesis of lung disease in obese patients.
PMID- 28426533
TI - HIV-DNA content in different CD4+ T-cell subsets correlates with CD4+ cell :
CD8+ cell ratio or length of efficient treatment.
AB - OBJECTIVES: HIV establishes a latent infection at different degrees within naive
(TN) or central (TCM) and effector memory (TEM) CD4 T cell. Studying patients in
whom HIV production was suppressed by combined antiretroviral therapy, our main
aim was to find which factors are related or can influence intracellular viral
reservoir in different CD4 T-cell subsets. METHODS: We enrolled 32 HIV patients
successfully treated for more than 2 years, with a CD4 T-cell count more than 500
cells/MUl and plasma viremia undetectable from at least 1 year. Proviral HIV-DNA,
the amount of cells expressing signal-joint T-cell receptor rearrangement
excision circles and telomere length were quantified by droplet digital PCR in
highly purified, sorted CD4 T-cell subsets; plasma IL-7 and IL-15 were measured
by ELISA. RESULTS: HIV-DNA was significantly lower in TN cells compared with TCM
or to TEM. Conversely, TN cells contained more signal-joint T-cell receptor
rearrangement excision circles compared with TCM or to TEM; no appreciable
changes were observed in telomere length. HIV-DNA content was significantly
higher in TN and TCM cells, but not in TEM, from patients with shorter time of
treatment, or in those with lower CD4 : CD8 ratio. CONCLUSION: Length of
treatment or recovery of CD4 : CD8 ratio significantly influences viral reservoir
in both TN and TCM. Measuring HIV-DNA in purified lymphocyte populations allows a
better monitoring of HIV reservoir and could be useful for designing future
eradication strategies.
PMID- 28426534
TI - Age-disparate relationships and HIV incidence in adolescent girls and young
women: evidence from Zimbabwe.
AB - OBJECTIVE: Age-disparate sexual relationships with older men may drive high rates
of HIV acquisition in young women in sub-Saharan Africa, but evidence is limited.
We investigate the association between age-disparate relationships and HIV
incidence in Manicaland, Zimbabwe. DESIGN: A general-population open-cohort study
(six surveys) (1998-2013). METHODS: A total of 3746 young women aged 15-24 years
participated in consecutive surveys and were HIV-negative at the beginning of
intersurvey periods. Last sexual partner age difference and age-disparate
relationships [intergenerational (>=10 years age difference) and
intragenerational (5-9 years) versus age-homogeneous (0-4 years)] were tested for
associations with HIV incidence in Cox regressions. A proximate determinants
framework was used to explore factors possibly explaining variations in the
contribution of age-disparate relationships to HIV incidence between populations
and over time. RESULTS: About 126 HIV infections occurred over 8777 person-years
(1.43 per 100 person-years; 95% confidence interval = 1.17-1.68). Sixty-five
percent of women reported partner age differences of at least 5 years. Increasing
partner age differences were associated with higher HIV incidence [adjusted
hazard ratio (aHR) = 1.05 (1.01-1.09)]. Intergenerational relationships tended to
increase HIV incidence [aHR = 1.78 (0.96-3.29)] but not intragenerational
relationships [aHR = 0.91 (0.47-1.76)]. Secondary education was associated with
reductions in intergenerational relationships [adjusted odds ratio (aOR) = 0.49
(0.36-0.68)]. Intergenerational relationships were associated with partners
having concurrent relationships [aOR = 2.59 (1.81-3.70)], which tended to
increase HIV incidence [aHR = 1.74 (0.96-3.17)]. Associations between age
disparity and HIV incidence did not change over time. CONCLUSION: Sexual
relationships with older men expose young women to increased risk of HIV
acquisition in Manicaland, which did not change over time, even with introduction
of antiretroviral therapy.
PMID- 28426535
TI - Frailty in HIV infected people: a new risk factor for bone mineral density loss.
AB - OBJECTIVE: The study aims to assess the association between bone mineral density
(BMD) and frailty in a cohort of HIV-infected patients. DESIGN: A cross-sectional
study in an HIV outpatient unit where nearly 1000 patients are monitored.
METHODS: Study participants undergoing bone densitometry were proposed an
evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and
the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self
reported exhaustion, physical activity, grip strength, chair stands, and slow
gait. Patients' characteristics were collected from an electronic medical record.
Associations of frailty with BMD and osteoporosis were tested using multivariate
linear and logit regression models, respectively. RESULTS: In total, 175 HIV
infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty
markers, osteopenia, and osteoporosis were comparable among sexes. Despite a
younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear
regression model adjusting by age, duration of HIV follow-up, BMI, smoking
status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a
negative association of spinal and femoral BMD with frailty according to SOF
criteria in women (P < 0.05). In men, SOF-defined frailty was associated with
osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model
adjusting for age, duration of HIV follow-up, CD4 nadir, CD4 T-cell count,
tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No
significant associations were found between BMD and CHS-defined frailty.
CONCLUSION: Our study shows that frailty according to SOF criteria is associated
with low spinal BMD values in female and osteoporosis in male HIV-infected
patients.
PMID- 28426536
TI - Exploring the Interaction Between Nursing Decision Making and Patient Outcomes in
2 European Cancer Centers: A Qualitative Study.
AB - BACKGROUND: In some clinical settings, nurses have difficulty describing the
outcomes of their caring activities. Understanding the reasons for this could
help nurse leaders to improve the effectiveness and visibility of nursing
practice and safeguard nurses' working conditions. OBJECTIVE: The aims of this
study were to understand how nurses working in 2 different adult cancer centers
make healthcare decisions and assess the respective outcomes on their patients.
METHODS: Through a constructivist grounded theory approach, we involved 15
clinical cancer nurses with different experiences and educational backgrounds and
6 nurse managers, working in 2 comprehensive cancer centers, 1 in Italy and 1 in
Switzerland. Data were collected in 2 phases using 20 semistructured interviews
and 9 field observations. RESULTS: Six macrocategories emerged: interacting with
situational factors, deciding relevant interventions, using multiple decision
making approaches, evaluating interventions and reporting them, pursuing
healthcare outcomes, and clarifying professional identity and roles. Nurses'
decision-making processes varied and were influenced by various factors, which
mutually influenced one another. This process was interpreted using an
explicative theory called "dynamic decision-making adaptation." CONCLUSIONS: The
present study showed how the aims, contents, and degree of autonomy in the
nurses' decision-making process are strongly influenced by the dialectic
interaction between professional and contextual factors, such as competency and
professional identity. IMPLICATIONS FOR PRACTICE: Cancer nurses could influence
their clinical practice by developing nursing competencies that effectively
resolve patients' problems. This is a key factor that nurses govern autonomously
and therefore a responsibility that involves the entire nursing educational,
organizational, and scientific leadership.
PMID- 28426537
TI - Supportive Care Needs and Association With Quality of Life of Mexican Adults With
Solid Cancers.
AB - BACKGROUND: Patients with cancer have supportive care needs. Studies that analyze
the relationship between supportive care needs and health-related quality of life
(HRQoL) are scarce. Cultural differences in supportive care needs and perceived
QoL are also worth analyzing. OBJECTIVE: The aim of this study was to assess the
association between supportive care needs and HRQoL of Mexican adults given a
diagnosis of solid cancers. METHODS: We performed a secondary data analysis of a
cross-sectional survey of 825 adult patients with cancer treated at the Oncology
Hospital of the Mexican Institute of Social Security. The QLQ-30 from the
European Organization for Research and Treatment of Cancer served to measure
HRQoL, and the Supportive Care Needs Questionnaire was used to ascertain the
needs. The analysis included multiple linear regression models for each HRQoL
domain controlled for demographic, clinical, and social support covariates.
RESULTS: There was an association between psychological needs with low scores in
the HRQoL domains of global health, emotional functioning, and increased fatigue.
Physical and daily living needs were associated with most HRQoL domains except
the emotional domain. Patient care needs were related to low scores in the
emotional and social functioning domains. Health systems and information needs
were associated with low scores on cognitive functioning. CONCLUSIONS: Physical,
psychological, patient care, and informational needs were associated with
decreased HRQoL of Mexican patients with cancer. IMPLICATIONS FOR PRACTICE:
Healthcare providers, including nurses, are encouraged to perform routine,
comprehensive evaluations of the supportive care needs and HRQoL of patients with
solid cancers to respond in a timely manner to their needs.
PMID- 28426538
TI - Five Phases of Recovery and Rehabilitation After Allogeneic Stem Cell
Transplantation: A Qualitative Study.
AB - BACKGROUND: For patients with a hematological malignancy, allogeneic stem cell
transplantation (alloSCT) is a treatment modality that may cause a wide range of
problems. Little is known about the process of recovery and rehabilitation and
the problems that alloSCT patients are confronted with during the first-year
posttransplant. OBJECTIVE: This study explored the problems of patients during
the first year after alloSCT, to better understand the process of recovery and
rehabilitation. METHODS: In a qualitative study, hemato-oncology patients were
interviewed 1-year posttransplant. The semistructured interviews were transcribed
verbatim, coded, and analyzed using constant comparative analysis. RESULTS: Ten
participants were included until saturation of data was reached. The patients had
experienced various problems and had gone through an individual process of
recovery and rehabilitation. Nevertheless, 5 phases could be distinguished: (1)
survive, (2) on the receiving end, (3) bring under control, (4) start
recuperation, and (5) retrospection. The duration of each phase varied between
patients. CONCLUSION: Although patients experienced individual problems after
alloSCT, they all followed a common pathway. Posttransplant care might be
improved by adjusting the care to the distinct phases that the patients pass
through. IMPLICATIONS FOR PRACTICE: Nurses can play an important role in
achieving improvements in posttransplant care by adjusting care to the individual
needs of patients within the distinct phases.Future nursing research should
confirm and refine this process of recovery and rehabilitation and assess the
effects of improvement measures in alloSCT patients and in other populations.
PMID- 28426539
TI - The Effect of Cancer Patients' and Their Family Caregivers' Physical and
Emotional Symptoms on Caregiver Burden.
AB - BACKGROUND: Although there is significant evidence that the family caregivers
(FCs) of cancer patients can experience significant caregiver burden and
symptoms, less is known about the relationships between FCs and patient
characteristics that influence caregiver burden. OBJECTIVE: The purpose of this
study was to examine the effect of cancer patients' and FCs' symptoms and
demographic characteristics on caregiver burden at initiation of the patients'
radiation treatment. METHODS: Two hundred eighty-one dyads of FCs and cancer
patients who received a diagnosis of breast, prostate, melanoma, lymphoma, and
head and neck cancers were recruited at the beginning of the patients' radiation
treatment. Measures of depression, sleep disturbance, fatigue, social support,
and self-efficacy were obtained from both FCs and cancer patients. The family
caregivers were also assessed for caregiver burden. Associations between
patients' and caregivers' symptoms and demographic characteristics and caregiver
burden were investigated using multivariate analyses. RESULTS: There were
significant associations between caregiver burden and the patient-related
variables such as self-efficacy (P = .02), sleep disturbance (P = .03), and
social support (P = .04). Among FC-related variables, higher scores of depression
(P < .01), fatigue (P < .01), and symptoms (P < .01) were significantly
associated with higher caregiver burden. Being a female, either as a patient or
FC, increased the likelihood of experiencing fatigue and sleep disturbance.
CONCLUSION: Caregiver burden in FCs is influenced by interplay of patients' and
their own symptoms and problems. These interdependencies exist from the beginning
of treatment. IMPLICATIONS FOR PRACTICE: Nurses should systematically assess the
problems and symptoms of the patients and FCs and support them from the time of
diagnosis to help prevent symptom development and deterioration.
PMID- 28426540
TI - Family Functioning Predicts End-of-Life Care Quality in Patients With Cancer:
Multicenter Prospective Cohort Study.
AB - BACKGROUND: Treating patients with cancer within a family setting is the accepted
standard of care and a hallmark of end-of-life (EoL) quality of care (QoC).
OBJECTIVE: The aim of this study was to determine whether family caregiver
functioning predicts EoL QoC received by terminally ill patients with cancer.
METHODS: Family caregivers of terminally ill patients with cancer (n = 264) were
enrolled from oncology inpatient and outpatient units of 12 large hospitals
located in different regions throughout South Korea. Caregivers were administered
self-reported questionnaires about family functioning and EoL QoC at the time of
an incurable cancer diagnosis, 4 to 6 weeks later, and again 2 to 3 months later.
Family functioning and QoC were measured using the family Apgar and Quality Care
Questionnaire-End of Life scales, respectively. RESULTS: Improved adaptability to
resource sharing and attention received predicted improved family relationships
for the 3 time points. Increased participation in decision making and
communication predicted improved individualized care and family relationships for
the 3 time points. Increased affection predicted improvements in dignity
conserving care and family relationships for the 3 time points. Improved
resolution regarding sharing time and satisfaction with commitments predicted
increases in all QoC domains for the 3 time points, including dignity-conserving
care, care by healthcare professionals, individualized care, and family
relationships. CONCLUSIONS: Family functioning may contribute to improved EoL QoC
of patients with terminal cancer. IMPLICATIONS FOR PRACTICE: Patients' family
caregivers are a valued source of affection and communicative support, improving
EoL QoC. More family-oriented cancer support systems can better maintain the
effectiveness of QoC until EoL.
PMID- 28426541
TI - Transfer Between Hospitals Is a Risk Situation for Patients After Lung Cancer
Surgery.
AB - BACKGROUND: Patients with lung cancer often undergo surgery shortly after
diagnosis. Despite undergoing extensive operation, many patients are transferred
to a local hospital a few days after surgery. Transitions between different
levels of care are risky due to common medication and follow-up errors.
OBJECTIVE: The study purpose was to explore patients' experiences of transfer
between hospitals after lung cancer surgery. The study aim was to improve the
quality of transitional care. METHODS: In-depth interviews with 14 patients with
lung cancer (6 men, 8 women) were conducted in the patients' homes. Interviews
were audiotaped, transcribed, and analyzed using the hermeneutic analysis method.
RESULTS: Patients' experience of transfer between hospitals after lung cancer
surgery is one of being in a caregiver gap characterized by feeling unprepared
and uncertain, feeling unprotected and not being cared for, and suffering because
of inadequate organization. Patients are vulnerable and at risk of injury before
and during transfer, as well as after arrival at local hospitals. CONCLUSIONS:
Study findings highlight a rarely considered risk of inadequate care before,
during, and after hospital transfer of vulnerable patients. Transition between
hospitals after lung cancer surgery is a part of patient care for which there are
no policies or care plans and a time during which the borders of responsibility
between caregivers are unclear. IMPLICATIONS FOR PRACTICE: It is important to
develop guidelines for clearly defined responsibilities during transfer between
hospitals. Healthcare providers need to plan transfers with the same rigor as
they do hospital care.
PMID- 28426542
TI - The Preliminary Effects of Massage and Inhalation Aromatherapy on Chemotherapy
Induced Acute Nausea and Vomiting: A Quasi-Randomized Controlled Pilot Trial.
AB - BACKGROUND: Despite pharmacological treatment, chemotherapy-induced nausea and
vomiting (CINV) are observed in patients. OBJECTIVE: This quasi-randomized
controlled pilot study evaluated the feasibility and preliminary effects of
massage and inhalation aromatherapies on chemotherapy-induced acute
nausea/vomiting. METHODS: Seventy-five patients with breast cancer were randomly
grouped into 1 of 3 groups: massage (n = 25), inhalation (n = 25), and control (n
= 25). The patients in the massage group received 20-minute aromatherapy foot
massage, whereas those in the inhalation group received 3-minute inhalation
aromatherapy before their second, third, and fourth chemotherapy cycles. The
control group underwent only the routine treatment. A nausea, vomiting, and
retching patient follow-up form was used to evaluate nausea severity by visual
analog scale and frequency of vomiting and retching. RESULTS: The incidence of
nausea and retching was significantly higher in the control group than in the
other groups in the third and fourth chemotherapy cycles (P < .001). Furthermore,
in these 2 cycles, the incidence of nausea and retching was significantly lower
in the massage group than in the inhalation group (P < .001). Nausea severity was
significantly lower among patients in the massage and inhalation groups than in
the control group in all 3 cycles (P < .001). CONCLUSION: Nausea severity was
significantly lower in the massage and inhalation aromatherapy groups than in the
control group. Nausea and retching incidence was reduced in the aromatherapy
groups compared with that in the control group. IMPLICATIONS FOR PRACTICE:
Nonpharmacological approaches are recommended for managing CINV. Massage and
inhalation aromatherapy seems promising regarding the management of CINV.
PMID- 28426544
TI - Neonatal abstinence syndrome: where are we, and where do we go from here?
AB - PURPOSE OF REVIEW: Over the last 15 years the prevalence of neonatal abstinence
syndrome (NAS) increased almost five-fold. A considerable diversity seems to
prevail in the management of NAS. This review provides an overview of factors
affecting the expression and course of NAS, and recent developments in NAS
assessment and treatment. RECENT FINDINGS: Apart from different pharmacological
and nonpharmacological treatment modalities, maturity of the infant and genetic
variations likely are (co)responsible for interpatient variability in NAS
severity, despite similar maternal exposure. Recent efforts concerning the
further development of NAS severity scoring systems focus on the development of
brief screening measures; in addition, pupil diameter and skin conductance have
been proposed as complements to observer-rated scales. The decrease in incidence
of NAS begins in the appropriate management of medication assisted treatment of
the mother. SUMMARY: Mitigating the negative outcomes for infants affected by
NAS, their mothers and the healthcare system implies, first and foremost,
developing and implementing an organized protocol for the management of NAS, and
the homogenous use of a standardized scoring system utilizing interobserver
reliability and a guide for medication initiation, maintenance, and weaning which
is consistent with traditional methods of treatment for neonates.
PMID- 28426545
TI - Sex differences in prescription opioid use.
AB - PURPOSE OF REVIEW: Recent literature focused on prescription opioids has
neglected sex differences in use. Here, we evaluated the recent literature (since
2015) examining sex differences in prescription opioid use. RECENT FINDINGS:
Between 2015 and 2016, our review found only eight articles addressing sex
differences in prescription opioid use mostly opioid misuse in North America
among individuals with chronic pain. Risk factors included depression, pain, and
polydrug use. In addition to that review, we had the opportunity to further
address sex differences in, and risk factors for, prescription opioid use through
a community engagement program, HealthStreet. Among the sample (n = 8525, Mage =
43.7 years, 58.6% women), approximately half reported use of prescription
opioids. Women were significantly more likely to report lifetime use (54.9 vs.
42.2%; P < 0.0001) and report cancer compared with men, yet, women with cancer
had a significantly reduced risk of using opioids compared with men with cancer
(odds ratio: 0.46; 95% confidence interval, 0.36-0.59). SUMMARY: Only a few
recently published studies analyzed sex differences related to prescription
opioid use. Findings from the literature and our data suggest women are more
likely to use prescription opioids compared with men. There is limited
information on sex differences in opioid use risk factors and outcomes and more
research in this area is warranted.
PMID- 28426546
TI - Methamphetamine use and dependence in vulnerable female populations.
AB - PURPOSE OF REVIEW: The study reviews recent publications on methamphetamine use
and dependence women in term of their epidemic, physical health impact,
psychosocial impacts, and also in the identified vulnerable issues. RECENT
FINDINGS: Studies of vulnerable populations of women are wide ranging and include
sex workers, sexual minorities, homeless, psychiatric patients, suburban women,
and pregnant women, in which amphetamine type stimulants (ATSs) are the most
commonly reported illicit drug used among them. The prenatal exposure of ATS
demonstrated the small for gestational age and low birth weight; however, more
research is needed on long-term studies of methamphetamine-exposed children.
Intimate partner violence (IPV) is commonly reported by female methamphetamine
users as perpetrators and victims. However, statistics and gendered power
dynamics suggest that methamphetamine-related IPV indicates a higher chance of
femicide. Methamphetamine-abusing women often have unresolved childhood trauma
and are introduced to ATS through families or partners. SUMMARY: Vulnerable
populations of women at risk of methamphetamine abuse and dependence. Impacts on
their physical and mental health, IPV, and pregnancy have been reported
continuing, which guide that empowering and holistic substance abuse are
necessary for specific group.
PMID- 28426548
TI - The MEDEX Northwest Physician Assistant Program: A Synopsis.
PMID- 28426547
TI - Excessive internet use in young women: What are the implications?
AB - PURPOSE OF REVIEW: There are considerable gender differences in youth engaging in
excessive internet use (EIU). This review provides updates based on the recent
literature focusing on the EIU in young women to describe its implications
including what it constitutes of, its correlates, sequelae and preventive and/or
treatment strategies. RECENT FINDINGS: Definition of EIU and its
conceptualization still requires refinement. Recent studies indicate a changing
trend towards female predominance of EIU. Women also differ in their internet use
compared with men regarding their preference in the internet content and online
activities, motives of use and factors related to access to the internet,
including the device, sociocultural restrictions, etc. The correlates and
sequelae of EIU encompass psychological, physical, biological, family and social
domains that could form the basis of identifying individuals at risk and
strategizing treatment. SUMMARY: The findings indicate the need for
standardization in definition and measures of EIU for better recognition of EIU
and identification of its at-higher-risk females. Effective preventive and
treatment measures are still limited by various methodology flaws outlined here.
PMID- 28426549
TI - Patient action: as means and end for chronic pain care.
PMID- 28426551
TI - Changing pain expectations: the role of social context and communication.
PMID- 28426550
TI - Neuropathic pain after chronic nerve constriction may not correlate with chloride
dysregulation in mouse trigeminal nucleus caudalis neurons.
AB - Changes in chloride reversal potential in rat spinal cord neurons have previously
been associated with persistent pain in nerve injury and inflammation models.
These changes correlate with a decrease in the expression of the potassium
chloride transporter, KCC2, and with increases in neuronal excitability. Here, we
test the hypothesis that similar changes occur in mice with neuropathic pain
induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI
ION). This model allows us to distinguish an acute pain phase (3-5 days after
injury) from a persistent pain phase (12-14 days after CCI-ION). Chronic
constriction injury of the trigeminal infraorbital nerve induced significant
decreases in mechanical pain thresholds in both the acute and persistent phases.
To estimate GABAA reversal potentials in neurons from trigeminal nucleus
caudalis, we obtained perforated patch recordings in vitro. GABAA reversal
potential decreased by 8% during the acute phase in unidentified neurons, but not
in GABAergic interneurons. However, at 12 to 14 days after CCI-ION, GABAA
reversal potential recovered to normal values. Quantitative real-time polymerase
chain reaction analysis revealed no significant changes, at either 3 to 5 days or
12 to 14 days after CCI-ION, in either KCC2 or NKCC1. These findings suggest that
CCI-ION in mice results in transient and modest changes in chloride reversal
potentials, and that these changes may not persist during the late phase. This
suggests that, in the mouse model of CCI-ION, chloride dysregulation may not have
a prominent role in the central mechanisms leading to the maintenance of chronic
pain.
PMID- 28426553
TI - Greater fear of visceral pain contributes to differences between visceral and
somatic pain in healthy women.
AB - This functional magnetic resonance imaging study addressed similarities and
differences in behavioral and neural responses to experimental visceral compared
with somatic pain stimuli and explored the contribution of fear of pain to
differences between pain modalities. In N = 22 healthy women, we assessed blood
oxygen level-dependent responses to rectal distensions and cutaneous heat stimuli
matched for perceived pain intensity. Fear of pain and pain unpleasantness were
assessed before and after scanning. Visceral pain was more fear evoking and more
unpleasant, and trial-by-trial intensity ratings failed to habituate across
trials (all interactions modality * time: P < 0.01). Differences in fear of pain
and pain intensity independently contributed to greater visceral pain
unpleasantness (combined regression model: R(2) = 0.59). We observed joint neural
activations in somatosensory cortex and frontoparietal attention network
(conjunction analysis: all pFWE <0.05), but distensions induced greater
activation in somatosensory cortex, dorsal and ventral anterior insula, dorsal
anterior and midcingulate cortices, and brainstem, whereas cutaneous heat pain
led to enhanced activation in posterior insula and hippocampus (all pFWE <0.05).
Fear of visceral pain correlated with prefrontal activation, but did not
consistently contribute to neural differences between modalities. These findings
in healthy women support marked differences between phasic pain induced by rectal
distensions vs cutaneous heat, likely reflecting the higher salience of visceral
pain. More studies with clinically relevant pain models are needed to discern the
role of fear in normal interindividual differences in the response to different
types of pain and as a putative risk factor in the transition from acute to
chronic pain.
PMID- 28426554
TI - Barking up the right tree: advancing our understanding and treatment of lymphoma
with a spontaneous canine model.
AB - PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as
an ideal model for studying the disease in humans and for developing new targeted
therapeutics for patients. Increasing interest by funding agencies, the private
sector, and multidisciplinary academic collaborations between different
disciplines and sectors now enables large knowledge gaps to be addressed and
provides additional proof-of-concept examples to showcase the significance of the
canine model. RECENT FINDINGS: The current review addresses the rationale for a
canine lymphoma model including the valuable role it can play in drug
development, serving as a link between mouse xenograft models and human clinical
trials and the infrastructure that is now in place to facilitate these studies.
Research in this field has focused on filling in the gaps to make the canine
lymphoma model more robust. These advances have included work on biomarkers,
detection of minimal residual disease, expansion of genomic and proteomic data,
and immunotherapy. SUMMARY: Incorporating pet dogs into the drug development
pipeline can improve the efficiency and predictability of preclinical models and
decrease the time and cost required for a therapeutic target to be translated
into clinical benefit.
PMID- 28426555
TI - Creating artificial lymphoid tissues to study immunity and hematological
malignancies.
AB - PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect
immune cell function and progression of disease. However, current animal models
are low throughput and a large number of human diseases are difficult to model in
animals. Animal models are less amenable to manipulation of tissue niche
components, signalling pathways, epigenetics, and genome editing than ex vivo
models. On the other hand, conventional 2D cultures lack the physiological
relevance to study precise microenvironmental interactions. Thus, artificial
tissues are being developed to study these interactions in the context of immune
development, function, and disease. RECENT FINDINGS: New bone marrow and lymph
node models have been created to, respectively, study microenvironmental
interactions in hematopoiesis and germinal center-like biology. These models have
also been extended to understand the effect of these interactions on the
progression and therapeutic response in leukemia, multiple myeloma, and lymphoma.
SUMMARY: 3D in-vitro immune models have elucidated new cellular, biochemical, and
biophysical interactions as potential regulatory mechanisms, therapeutic targets,
or biomarkers that previously could not be studied in animal models and
conventional 2D cultures. Incorporation of advanced biomaterials, microfluidics,
genome editing, and single-cell analysis tools will enable further studies of
function, driver mutations, and tumor heterogeneity. Continual refinement will
help inform the development of antibody and cell-based immunotherapeutics and
patient-specific treatment plans.
PMID- 28426556
TI - Limited transthoracic echocardiogram: "This is how I do it".
PMID- 28426558
TI - Combat surgical workload in Operation Iraqi Freedom and Operation Enduring
Freedom: The definitive analysis.
AB - BACKGROUND: Relatively few publications exist on surgical workload in the
deployed military setting. This study analyzes US military combat surgical
workload in Iraq and Afghanistan to gain a more thorough understanding of
surgical training gaps and personnel requirements. METHODS: A retrospective
analysis of the Department of Defense Trauma Registry was performed for all Role
2 (R2) and Role 3 (R3) military treatment facilities from January 2001 to May
2016. International Classification of Diseases, Ninth Revision, Clinical
Modification procedure codes were grouped into 18 categories based on functional
surgical skill sets. The 189,167 surgical procedures identified were stratified
by role of care, month, and year. Percentiles were calculated for the number of
procedures for each skill set. A literature search was performed for publications
documenting combat surgical workload during the same period. RESULTS: A total of
23,548 surgical procedures were performed at R2 facilities, while 165,619
surgical procedures were performed at R3 facilities. The most common surgical
procedures performed overall were soft tissue (37.5%), orthopedic (13.84%),
abdominal (13.01%), and vascular (6.53%). The least common surgical procedures
performed overall were cardiac (0.23%), peripheral nervous system (0.53%), and
spine (0.34%).Mean surgical workload at any point in time clearly
underrepresented those units in highly kinetic areas, at times by an order of
magnitude or more. The published literature always demonstrated workloads well in
excess of the 50th percentile for the relevant time period. CONCLUSIONS: The
published literature on combat surgical workload represents the high end of the
spectrum of deployed surgical experience. These trends in surgical workload
provide vital information that can be used to determine the manpower needs of
future conflicts in ever-changing operational tempo environments. Our findings
provide surgical types and surgical workload requirements that will be useful in
surgical training and placement of medical assets in future conflicts. LEVEL OF
EVIDENCE: Epidemiologic study, level III; Care management, level III.
PMID- 28426557
TI - Loop ileostomy versus total colectomy as surgical treatment for Clostridium
difficile-associated disease: An Eastern Association for the Surgery of Trauma
multicenter trial.
AB - OBJECTIVES: The mortality of patients with Clostridium difficile-associated
disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI)
was introduced as an alternative procedure to total colectomy (TC) for CDAD by a
single-center study. To date, no reproducible results have been published. The
objective of this study was to compare these two procedures in a multicentric
approach to help the surgeon decide what procedure is best suited for the patient
in need. METHODS: This was a retrospective multicenter study conducted under the
sponsorship of the Eastern Association for the Surgery of Trauma. Demographics,
medical history, clinical presentation, APACHE score, and outcomes were
collected. We used the Research Electronic Data Capture tool to store the data.
Mann-Whitney (continuous data) and Fisher exact (categorical data) were used to
compare TC with LI. Logistic regression was performed to determine predictors of
mortality. A propensity score analysis was done to control for potential
confounders and determine adjusted mortality rates by procedure type. RESULTS: We
collected data from 10 centers of patients who presented with CDAD requiring
surgery between July 1, 2010 and July 30, 2014. Two patients died during the
surgical procedure, leaving 98 individuals in the study. The overall mortality
was 32%, and 75% had postoperative complications. Median age was 64.5 years; 59%
were male. Concerning preoperative patient conditions, 54% were on pressors, 47%
had renal failure, and 36% had respiratory failure. When comparing TC and LI,
there was no statistical difference regarding these conditions. Univariate
preprocedure predictors of mortality were age, lactate, timing of operation,
vasopressor use, and acute renal failure. There was no statistical difference
between the APACHE score of patients undergoing either procedure (TC, 22 vs LI,
16). Adjusted mortality (controlled for preprocedure confounders) was
significantly lower in the LI group (17.2% vs 39.7%; p = 0.002). CONCLUSIONS:
This is the first multicenter study comparing TC with LI for the treatment of
CDAD. In this study, LI carried less mortality than TC. In patients without
contraindications, LI should be considered for the surgical treatment of CDAD.
LEVEL OF EVIDENCE: Therapeutic study, level III.
PMID- 28426559
TI - Computed tomography evidence of fluid in the hernia sac predicts surgical site
infection following mesh repair of acutely incarcerated ventral and groin
hernias.
AB - BACKGROUND: Mesh placement during repair of acutely incarcerated ventral and
groin hernias is associated with high rates of surgical site infection (SSI). The
utility of preoperative computed tomography (CT) in this setting is unclear. We
hypothesized that CT evidence of bowel wall compromise would predict SSI while
accounting for physiologic parameters. METHODS: We performed a 4-year
retrospective cohort analysis of 50 consecutive patients who underwent mesh
repair of acutely incarcerated ventral or groin hernias. We analyzed chronic
disease burden, acute illness severity, CT findings, operative management, and
herniorrhaphy-specific outcomes within 180 days. The primary outcome was SSI by
the Centers for Disease Control and Prevention criteria. Multiple logistic
regression was performed to identify independent predictors of SSI. RESULTS:
Eighty-four percent of all patients were American Society of Anesthesiologists
class III or IV, 28% were active smokers, and mean body mass index (BMI) was 35
kg/m. Fifty-four percent had ventral hernias, 40% had inguinal hernias, and 6%
had femoral or combined inguinal/ femoral hernias. Seventy percent of
preoperative CT scans had features suggesting bowel compromise, abdominal free
fluid, or fluid in the hernia sac. Surgical site infection occurred in 32% of all
patients (8% superficial, 24% deep or organ/space). The strongest predictors of
SSI were CT evidence of fluid in the hernia sac (odds ratio [OR], 8.3; 95%
confidence interval [CI], 1.7-41), initial heart rate 90 beats/min or greater
(OR, 6.3; 95% CI, 1.1-34), and BMI 35 kg/m or greater (OR, 5.8; 95% CI, 1.2-28).
Surgical site infection rates were significantly higher among patients who had CT
evidence of fluid in the hernia sac (56% vs. 19%, p = 0.012). CONCLUSIONS: More
than half of all patients with CT scan evidence of fluid in the hernia sac
developed an SSI. Computed tomography evidence of fluid in the hernia sac was the
strongest predictor of SSI, followed by heart rate and BMI. Together, these
parameters identify high-risk patients for whom better strategies are needed to
avoid SSI without sacrificing durability. LEVEL OF EVIDENCE: Prognostic study,
level III; Therapeutic, level IV.
PMID- 28426560
TI - Universal screening for intimate partner and sexual violence in trauma patients:
An EAST multicenter trial.
AB - BACKGROUND: A single-center trial recently demonstrated a prevalence of 14% of
intimate partner and sexual violence (IPSV) among both male and female trauma
patients, regardless of mechanism of injury. We aimed to determine if this
phenomenon was similar to rates in other trauma centers by assessing the
feasibility of universal screening and determining the prevalence and association
of IPSV with other trauma-associated comorbidities. METHODS: We designed an
Eastern Association for the Surgery of Trauma-supported multicenter, prospective
observational cohort study involving four Level I trauma centers throughout the
United States. Screening occurred from March 2015 to April 2016. We performed
universal screening of adult trauma patients using the validated HITS (Hurt,
Insult, Threaten, Scream) and SAVE (sexual violence) screening surveys. Trauma
recidivism, substance use, and mental illness were also measured and were
classified as "trauma-associated comorbidities." Chi-squared test compared
categorical variables with significance at p <0.05. Parametric data is presented
as mean +/- standard deviation. RESULTS: A total of 2,034 eligible trauma
patients were screened by clinical social workers at each site over 1 year. The
mean age was 37.05 +/- 20.32 with 63% men, 37% women, and one transgendered
participant. The overall rate of IPSV was 11.4%. The proportion of positive
screens for men was 9.3%, with variability between centers (3.8-72.7%), and for
women was 16.1% (15.3-50.0%) (p < 0.001). The transgendered patient screened
positive for IPSV. Of patients who screened positive for IPSV, 60.0% had one or
more trauma-associated comorbidity compared to 15.1% of patients who screened
negative (p < 0.001). CONCLUSION: More than one in nine trauma patients is at
risk of IPSV, regardless of gender or mechanism of injury. IPSV may be a risk
factor for other trauma-associated comorbidities. LEVEL OF EVIDENCE:
Prognostic/Epidemiologic, level II; Care Management, level III.
PMID- 28426561
TI - Unfractionated heparin versus low-molecular-weight heparin for venous
thromboembolism prophylaxis in trauma.
AB - BACKGROUND: Venous thromboembolism (VTE) is a common complication in trauma
patients. Pharmacologic prophylaxis is utilized in trauma patients to reduce
their risk of a VTE event. The Eastern Association for the Surgery of Trauma
guidelines recommend use of low-molecular-weight heparin (LMWH) as the preferred
agent in these patients. However, there is literature suggesting that
unfractionated heparin (UFH) is an acceptable, and less costly, alternative VTE
prophylaxis agent with equivalent efficacy in trauma patients. We examined data
from the Michigan Trauma Quality Improvement Program to perform a comparative
effectiveness study of UFH versus LMWH on outcomes for trauma patients. METHODS:
We conducted an analysis of the Michigan Trauma Quality Improvement Program data
from January 2012 to December 2014. The data set contains information on date,
time, and drug type of the first dose of VTE prophylaxis. Thirty-seven thousand
eight hundred sixty-eight patients from 23 hospitals were present with an Injury
Severity Score of 5 or greater and hospitalization for more than 24 hours.
Patients were excluded if they died within 24 hours or received no pharmacologic
VTE prophylaxis or agents other than UFH or LMWH while admitted to the hospital.
We compared patients receiving LMWH to those receiving UFH. Outcomes assessed
were VTE event, pulmonary embolism, deep vein thrombosis, and mortality during
hospitalization. We used a generalized estimating equation approach to fit
population-averaged logistic regression models with the type of first dose of VTE
prophylaxis as the independent variable. Unfractionated heparin was considered
the reference value. Timing of the first dose of VTE prophylaxis was entered into
the model in addition to standard covariates. Odds ratios were generated for each
of the dependent variables of interest. RESULTS: The analysis cohort consisted of
18,010 patients. Patients administered LMWH had a decreased risk of mortality
(odds ratio, 0.64; confidence interval, 0.49-0.83), VTE (odds ratio, 0.67;
confidence interval, 0.53-0.84), pulmonary embolism (odds ratio, 0.53; confidence
interval, 0.35-0.79), and deep vein thrombosis (odds ratio, 0.73; confidence
interval, 0.57-0.95) when compared with UFH following risk adjustment and
accounting for hospital effect. The reduced risk of a VTE event for patients
receiving LMWH was most pronounced for patients in the lower injury-severity
categories. CONCLUSIONS: In our examination of VTE prophylaxis drug
effectiveness, LMWH was found to be superior to UFH in reducing the incidence of
mortality and VTE events among trauma patients. Therefore, LMWH should be the
preferred VTE prophylaxis agent for use in hospitalized trauma patients. LEVEL OF
EVIDENCE: Therapeutic, level III.
PMID- 28426562
TI - Asymptomatic cervical spine fractures: Current guidelines can fail older
patients.
AB - BACKGROUND: Older adults represent a growing proportion of trauma patients
treated in the United States, and cervical spine (c-spine) fracture is an injury
that is increasingly common in this population. Neck pain is a major component of
current clinical clearance guidelines, but some older adults with c-spine
fractures report no neck pain after injury. The objective of this study was to
investigate the frequency at which c-spine fractures were unassociated with neck
pain in an aging population. METHODS: A retrospective review was performed for
patients 55 years or older with a c-spine fracture during a 4-year study period.
All patients had a Glasgow Coma Scale score of 15 and were considered
asymptomatic if they did not complain of neck pain on initial presentation,
denied tenderness to palpation of the c-spine on examination, and were without
neurologic deficit. Differences between groups were assessed with Kruskal-Wallis
and chi tests. RESULTS: Of 173 patients with c-spine fractures, 36 (21%) were
asymptomatic and reported no neck pain on presentation or on examination. The
group without neck pain had higher median injury severity scores (15 vs 10; p <
0.001), were more likely to have another injured body region (69% vs 42%; p =
0.004), and had longer hospitalization (7 vs 5 days; p = 0.008) than patients
with neck pain. Twenty-two percent of the symptomatic group and 19% of the
asymptomatic group required halo, fusion, or other surgical intervention.
DISCUSSION: Study results indicate that one fifth of patients with a c-spine
fracture reported no pain on initial presentation and denied tenderness to
palpation on examination. The presence or absence of pain may be an unreliable
indicator of c-spine fracture in an aging population. When used in conjunction
with existing clearance guidelines, denial of pain may lead to missed injury. We
recommend liberal c-spine imaging for older trauma patients with significant
mechanism of trauma. LEVEL OF EVIDENCE: Therapeutic study, level III.
PMID- 28426563
TI - Routine inclusion of long-term functional and patient-reported outcomes into
trauma registries: The FORTE project.
AB - BACKGROUND: The National Academies of Sciences, Engineering, and Medicine
(formerly the Institute of Medicine) recently recommended inclusion of
postdischarge health-related quality of life (HRQoL) and patient-reported
outcomes (PROs) metrics to benchmark the quality of trauma care. Currently, these
measures are not routinely collected at most trauma centers. We sought to
determine the feasibility and value of adding such long-term outcome measures to
trauma registries. METHODS: As part of the FORTE (Functional Outcomes and
Recovery after Trauma Emergencies) project, we included patients with an Injury
Severity Score of 9 or greater, admitted to the Brigham and Women's Hospital in
Boston, MA, who were identified retrospectively using the institutional trauma
registry and contacted 6 or 12 months after injury to participate in a telephone
survey evaluating HRQoL (Short Form 12 [SF-12]), PROs (Trauma Quality of Life),
posttraumatic stress disorder, return to work, residential status, and health
care utilization. RESULTS: Data were collected for 171 of 394 eligible patients:
85/189 (45%) at 6 months and 86/205 (42%) at 12 months; 25%/29% (6/12 months)
patients could not be contacted, 15%/16% (6/12 months) declined to participate,
and 15%/13% (6/12 months) were interested in participating at another time but
were not reached again. Approximately 20% patients screened positive for
posttraumatic stress disorder, and half had not yet returned to work. There were
significant reductions in SF-12 physical composite scores relative to population
norms (mean, 50 [SD, 10]) at 6 months (mean, 44; 95% confidence interval [CI], 41
47) and 12 months (45; 95% CI, 42-47); no difference was noted in the SF-12
mental composite scores (6 months: 51 [95% CI, 48-54]; 12 months: 50 [95% CI, 46
53]). CONCLUSIONS: Trauma patients reported considerable impairment 6 and 12
months after injury. Routine collection of PROs and HRQoL provides important data
regarding trauma outcomes beyond mortality and will enable the development of
quality improvement metrics that better reflect patients' postinjury experiences.
Improved and alternate methods for collection of these data need to be developed
to enhance response rates before widespread adoption across trauma centers in the
United States. LEVEL OF EVIDENCE: Prognostic/epidemiologic, level II;
Therapeutic, level III.
PMID- 28426564
TI - Report on NPUAP Session: Untangling the Terminology of Unavoidable Pressure
Injuries, Terminal Ulcers, and Skin Failure.
PMID- 28426565
TI - Unavoidable Pressure Injuries, Terminal Ulceration, and Skin Failure: In Search
of a Unifying Classification System.
PMID- 28426567
TI - How Will CMS Edit Therapy Services to Reflect Coding Changes?
PMID- 28426568
TI - Looking Beyond the Cell in Cellulitis.
AB - BACKGROUND: Patients with erythematous skin are likely to receive a diagnosis of
cellulitis; however, the accuracy of this diagnosis is approximately only 33%.
The diagnosis of cellulitis should be made only after a thorough evaluation of
all possible differential diagnoses. Cellulitis may be a primary process
(superficial spreading infective process involving only the epidermis and dermis)
versus a secondary (reactive) process incited by a subcutaneous process, such as
an abscess, tenosynovitis, necrotizing fasciitis, and osteomyelitis. CASE
PRESENTATION: A 50-year-old man was admitted to a general hospital with the
diagnosis of cellulitis. He was initially treated with systemic antibiotics
without improvement. Following consultation with a wound management physician,
the patient received a diagnosis of a pretibial abscess and was treated with
surgical evacuation and postoperative systemic antibiotic therapy guided by
tissue cultures. A postoperative wound was successfully treated with inelastic
compression therapy. CONCLUSIONS: This case demonstrates the potential for
misdiagnosis when evaluating erythematous skin. Furthermore, concluding that the
erythema is due to a primary cellulitis may result in monotherapy with systemic
antimicrobial agents. In such cases, making a correct diagnosis through a
skillful and complete physical examination of the patient, coupled with
appropriate investigations, will lead to the best possible outcome. A
comprehensive treatment approach may include systemic antimicrobials, as well as
surgical options and compression therapy.
PMID- 28426569
TI - Salve and Burdock: A Safe, Effective Amish Remedy for Treatment of Traumatic
Wounds?
AB - BACKGROUND: Amish patients show a demonstrated preference for traditional, herbal
remedies over modern medical interventions such as skin grafting. One such remedy
is a mixture of Burn & Wound Ointment (B & W Ointment; Holistic Acres, LLC;
Newcomerstown, Ohio) and steeped burdock leaves. Although both have demonstrated
some antimicrobial and wound healing properties, burdock and/or the combination
of B & W Ointment and burdock has never been studied to determine its purported
ability to reduce pain, prevent infection, and accelerate wound healing. METHODS:
A retrospective chart review was performed on 6 Amish patients treated with salve
and burdock leaves instead of skin grafting following complex traumatic wounds to
determine whether the traditional treatment incurred any patient harm. RESULTS:
The time of wound epithelialization and healing complications were noted, among
other data points. Time to full epithelialization ranged from 1 to 7 months. Time
to full wound healing was proportional to wound size. CONCLUSIONS: Although the
treatment presented here is unconventional, it did not cause harm to the patients
studied.
PMID- 28426570
TI - Susceptibility of Trichopyton mentagrophytes to Visible Light Wavelengths.
AB - OBJECTIVE: To determine whether a blue light (405 nm) could inhibit the growth of
Trichopyton mentagrophytes without using a photosensitizing material as part of
the treatment protocol. DESIGN: Basic physiologic randomized trial using
laboratory specimens (T mentagrophytes). INTERVENTIONS/METHODS: Plated on a
growth medium, T mentagrophytes were exposed to 3 to 5 administrations of blue
light at 20 J/cm over 28 hours. Following 7 days of incubation, colony-forming
units were counted and compared with nonirradiated controls. RESULTS: The study
found 3, 4, and 5 administrations of blue light produced significant inhibition
of T mentagrophytes (P < .05); 4 and 5 applications produced the greatest
inhibition of growth (84.7% and 93.6% kill rates, respectively). CONCLUSIONS: The
application of 405-nm light at a dose of 20 J/cm is an effective in vitro
inhibitor of T mentagrophytes. To give results similar to those seen when a
photosensitizing material is included, 3 to 5 applications of this wavelength and
dose condition delivered over 28 hours is likely needed.
PMID- 28426571
TI - Growth Differentiation Factor 5 Accelerates Wound Closure and Improves Skin
Quality During Repair of Full-Thickness Skin Defects.
AB - BACKGROUND: A fast and stable wound closure is important, especially for extended
and unstable wounds found after burn injuries. Growth can regulate a variety of
cellular processes, including those involved in wound healing. Growth
differentiation factor 5 (GDF-5) can accelerate fibroblast cell migration, cell
proliferation, and collagen synthesis, which are essential for wound healing.
Nevertheless, no standardized evaluation of the effect of GDF-5 on the healing of
full-thickness wounds has been published to date. METHODS: Five full-thickness
skin defects were created on the backs of 6 minipigs. Three wounds were treated
with GDF-5 in different concentrations with the help of a gelatin-collagen
carrier, and 2 wounds served as control group. The first was treated with the
gelatin carrier and an Opsite film (Smith & Nephew, Fort Worth, Texas), and the
other was treated solely with an Opsite film that was placed above all wounds and
renewed every second day. RESULTS: Growth differentiation factor 5 accelerates
wound closure (10.91 [SD, 0.99] days) compared with treatment with the carrier
alone (11.3 [SD, 1.49] days) and control wounds (13.3 [SD, 0.94] days). Epidermal
cell count of wounds treated with GDF-5 revealed a higher number of cells
compared with the control group. In addition, mean epidermal thickness was
significantly increased in GDF-5-treated wounds compared with the control wounds.
CONCLUSIONS: Because of its ability to improve skin quality, GDF-5 should be
considered when developing composite biomaterials for wound healing.
PMID- 28426572
TI - Nonhealing Ulcers in Patients with Tophaceous Gout: A Systematic Review.
AB - GENERAL PURPOSE: To provide information from a review of the literature about
chronic ulcers associated with tophaceous gout. TARGET AUDIENCE: This continuing
education activity is intended for physicians, physician assistants, nurse
practitioners, and nurses with an interest in skin and wound care. LEARNING
OBJECTIVES/OUTCOMES: After participating in this educational activity, the
participant should be better able to:1. Identify the pathophysiology of
tophaceous gout, its presentation, phases, and common comorbidities.2. Evaluate
the findings in this review regarding effectiveness of interventions for chronic
tophaceous ulcers. ABSTRACT: OBJECTIVE: Treating chronic ulcers associated with
tophaceous gout is an uncommon but important clinical challenge. However,
treatments vary greatly from topical therapies, to debridements, to free flap
wound coverage. To the authors' knowledge, this is the first study to assemble
and compare these different approaches in order to guide effective treatment.
DATA SOURCES: An electronic search of MEDLINE (PubMed) was conducted. Search
terms included (gout and ulcer) not "peptic ulcer," and (gout, chronic wound) or
(gout, nonhealing wound). STUDY SELECTION: Studies that discussed the
presentation, characterization, or treatment of gout-associated wounds were
included. The literature search yielded 9 case reports and case series; there
were no randomized controlled studies or reviews. DATA EXTRACTION: Patient and
wound characteristics, treatment approaches, and outcomes were noted. DATA
SYNTHESIS: The 82% of 22 patients were male, aged 36 to 95 years. Three patients
had not been previously diagnosed with gout, whereas others had received a
diagnosis 2 to 35 years prior to presentation with an ulcer. Many patients had
comorbidities including diabetes and peripheral vascular disease. Most of the 43
total ulcers occurred on the feet. Treatments included topical 3% citric acid in
petroleum jelly, allogeneic culture dermal substitute, silver-containing dressing
and heterologous lyophilized collagen, debridements, and free flap coverage.
CONCLUSIONS: Chronic tophaceous wounds are a worldwide problem. Although
physicians report some successes with different treatments, controlled studies
are needed to determine the most effective approach and to identify risk factors
and preventive strategies.
PMID- 28426573
TI - Quality Payment Program: Advancing Care Information Performance Category: Part 1.
PMID- 28426574
TI - Nonhealing Ulcers in Patients with Tophaceous Gout: A Systematic Review.
PMID- 28426575
TI - Tipping the Scales for Cancer Surgery Outcomes: Anesthetic Influences on Cancer
Progression.
PMID- 28426576
TI - Personalized Intrathecal Drug Delivery: Models, Targets, and Approaches.
PMID- 28426577
TI - Can the Perioperative Anesthesia Care of Patients With Cancer Affect Their Long
term Oncological Outcomes?
PMID- 28426578
TI - Plasma Transfusion as Bleeding Prophylaxis in the Critically Ill.
PMID- 28426579
TI - The PLAIN Truth: Caring for the Amish: What Every Anesthesiologist Should Know.
PMID- 28426580
TI - Neuraxial Labor Analgesia: Does It Influence the Outcomes of Labor?
PMID- 28426581
TI - Anesthesiology and New Models of Perioperative Care: What Will Help Move the
Needle?
PMID- 28426582
TI - Women, Minorities, and Leadership in Anesthesiology: Take the Pledge.
PMID- 28426583
TI - The Law of Unintended Consequences Can Never Be Repealed: The Hazards of Random
Urine Drug Screening of Anesthesia Providers.
PMID- 28426584
TI - Neuromuscular Monitoring as the Art of Probability.
PMID- 28426585
TI - Modeling Spinal Intrathecal Drug Distribution: The Challenge of Defining and
Predicting Cerebrospinal Fluid Dynamics.
PMID- 28426586
TI - Predictive Modeling of Massive Transfusion Requirements During Liver
Transplantation and Its Potential to Reduce Utilization of Blood Bank Resources.
AB - BACKGROUND: Patients undergoing liver transplantation frequently but
inconsistently require massive blood transfusion. The ability to predict massive
transfusion (MT) could reduce the impact on blood bank resources through
customization of the blood order schedule. Current predictive models of MT for
blood product utilization during liver transplantation are not generally
applicable to individual institutions owing to variability in patient population,
intraoperative management, and definitions of MT. Moreover, existing models may
be limited by not incorporating cirrhosis stage or thromboelastography (TEG)
parameters. METHODS: This retrospective cohort study included all patients who
underwent deceased-donor liver transplantation at the Johns Hopkins Hospital
between 2010 and 2014. We defined MT as intraoperative transfusion of > 10 units
of packed red blood cells (pRBCs) and developed a multivariable predictive model
of MT that incorporated cirrhosis stage and TEG parameters. The accuracy of the
model was assessed with the goodness-of-fit test, receiver operating
characteristic analysis, and bootstrap resampling. The distribution of correct
patient classification was then determined as we varied the model threshold for
classifying MT. Finally, the potential impact of these predictions on blood bank
resources was examined. RESULTS: Two hundred three patients were included in the
study. Sixty (29.6%) patients met the definition for MT and received a median
(interquartile range) of 19.0 (14.0-27.0) pRBC units intraoperatively compared
with 4.0 units (1.0-6.0) for those who did not satisfy the criterion for MT. The
multivariable model for predicting MT included Model for End-stage Liver Disease
score, whether simultaneous liver and kidney transplant was performed, cirrhosis
stage, hemoglobin concentration, platelet concentration, and TEG R interval and
angle. This model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit
test P = .45) and good discrimination (c statistic: 0.835; 95% confidence
interval, 0.781-0.888). A probability cutoff threshold of 0.25 was found to
misclassify only 4 of 100 patients as unlikely to experience MT, with the
majority such misclassifications within 4 units of the working definition for MT.
For this threshold, a preoperative blood ordering schedule that allocated 6 units
of pRBCs for those unlikely to experience MT and 15 for those who were likely to
experience MT would prevent unnecessary crossmatching of 338 units/100
transplants. CONCLUSIONS: When clinical and laboratory parameters are included, a
model predicting intraoperative MT in patients undergoing liver transplantation
is sufficiently accurate that its predictions could guide the blood order
schedule for individual patients based on institutional data, thereby reducing
the impact on blood bank resources. Ongoing evaluation of model accuracy and
transfusion practices is required to ensure continuing performance of the
predictive model.
PMID- 28426587
TI - Reduced Blood Viscosity Plays Minor Role in Regional Blood Flow Increases During
Acute Normovolemic Hemodilution.
PMID- 28426588
TI - In Response.
PMID- 28426590
TI - In Response.
PMID- 28426589
TI - Open Access, Crowd-Sourced Repository of Anesthesia Information (Wiki-Anesthesia)
as Antidote to Inaccurate Internet-Based Resources.
PMID- 28426591
TI - Overregulation Revisited.
PMID- 28426592
TI - In Response.
PMID- 28426593
TI - Showing and Telling! Screencasts for Enhanced Feedback on Student Writing.
PMID- 28426594
TI - Enhancing Cross-Curricular Connectedness and Collaboration From Associate Degree
to Clinical Doctorate.
PMID- 28426595
TI - Creative Strategies for Teaching Millennial Nursing Students.
PMID- 28426596
TI - Worldwide Abortion Rates and Access to Contraception.
PMID- 28426597
TI - Accommodating Immigrant Women's Preferences for Female Health Care Providers.
AB - OBJECTIVE: To investigate obstetricians' perspectives of the importance, effect,
and challenges of providing intrapartum care to immigrant women who request a
female obstetrician. METHODS: A focused ethnography was conducted at a large
teaching hospital, which serves a high proportion of immigrant clientele
(predominantly North or East African, Middle Eastern, and South Asian) in
Edmonton, Alberta, Canada. Data collection comprised single, semistructured
interviews with a purposive sample of 20 obstetric health care providers (10
resident and 10 staff obstetricians). Interviews were audio-recorded and
transcribed verbatim. Data were managed with Quirkos and analyzed using thematic
analysis. RESULTS: A total of 13 female and seven male physicians were
interviewed. Physicians recognized the validity of immigrant women's preference
and requests for female health care providers and expressed sympathy for them.
However, they were also resistant and expressed several concerns about
accommodating these requests, including fear of perpetuating and exacerbating
gender inequalities in medicine, the extent to which patient decision-making was
coercion-free, the ability of the health system to meet the demands, and
implications for training and quality of care. CONCLUSION: Although physicians
were sympathetic to immigrant women's requests for female obstetricians, they
placed greater value on maintaining gender equity both within the medical
profession and in wider society and resisted accommodating gender-of-health-care
provider requests. Our qualitative study suggests a need for greater research to
inform policy that meets the professional and personal values of both physicians
and patients.
PMID- 28426598
TI - Listen to Women.
PMID- 28426599
TI - Blood Loss as a Function of Body Surface Area: Redefining Parameters of Obstetric
Blood Loss.
PMID- 28426600
TI - In Reply.
PMID- 28426601
TI - Interpregnancy Interval After Termination of Pregnancy and the Risks of Adverse
Outcomes in Subsequent Birth.
PMID- 28426602
TI - In Reply.
PMID- 28426603
TI - Operationalizing 17alpha-Hydroxyprogesterone Caproate to Prevent Recurrent
Preterm Birth: Definitions, Barriers, and Next Steps.
PMID- 28426604
TI - In Reply.
PMID- 28426605
TI - Maternal Deaths From Suicide and Overdose in Colorado, 2004-2012.
PMID- 28426606
TI - Preeclampsia and Long-term Risk of Maternal Retinal Disorders.
PMID- 28426607
TI - In Reply.
PMID- 28426608
TI - Attempted and Successful Vacuum-Assisted Vaginal Delivery by Prepregnancy Body
Mass Index.
PMID- 28426613
TI - Practice Bulletin No. 178 Summary: Shoulder Dystocia.
PMID- 28426614
TI - Committee Opinion No. 698 Summary: Hormone Therapy in Primary Ovarian
Insufficiency.
AB - Primary ovarian insufficiency describes a spectrum of declining ovarian function
and reduced fecundity due to a premature decrease in initial follicle number, an
increase in follicle destruction, or poor follicular response to gonadotropins.
The sequelae of primary ovarian insufficiency include vasomotor symptoms,
urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and
increased all-cause mortality. In women with primary ovarian insufficiency,
systemic hormone therapy (HT) is an effective approach to treat the symptoms of
hypoestrogenism and mitigate long-term health risks if there are no
contraindications to treatment. Hormone therapy is indicated to reduce the risk
of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve
the quality of life of women with primary ovarian insufficiency. Although
exogenous estrogen replacement is recommended for women with primary ovarian
insufficiency, data comparing various hormonal regimens for disease prevention,
symptom amelioration, and safety are lacking in this population. As a first-line
approach, HT (either orally or transdermally) that achieves replacement levels of
estrogen is recommended. Combined hormonal contraceptives prevent ovulation and
pregnancy more reliably than HT; despite only modest odds of spontaneous
pregnancy in women with primary ovarian insufficiency, this is a critical
consideration for those who deem pregnancy prevention a priority. Treatment for
all women with primary ovarian insufficiency should continue until the average
age of natural menopause is reached (age 50-51 years). Finally, considering the
challenges that adolescents and young women may face in coping with the physical,
reproductive, and social effects of primary ovarian insufficiency, comprehensive
longitudinal management of this condition is essential.
PMID- 28426615
TI - Committee Opinion No. 699: Adolescent Pregnancy, Contraception, and Sexual
Activity.
AB - In 2015, the birth rate among U.S. adolescents and young adults (aged 15-19
years) reached a historic low at 22.3 per 1,000 women. Despite positive trends,
the United States continues to have the highest adolescent pregnancy rate among
industrialized countries with data. Racial and ethnic disparities in adolescent
pregnancy rates continue to exist, as do state-based differences in pregnancy,
birth, and abortion rates. The American College of Obstetricians and
Gynecologists supports access for adolescents to all contraceptive methods
approved by the U.S. Food and Drug Administration. In the absence of
contraindications, patient choice should be the principal factor in prescribing
one method of contraception over another. Dual method use-the use of condoms in
combination with more effective contraceptive methods to protect against sexually
transmitted infections and unwanted pregnancy-is the ideal contraceptive practice
for adolescents. Just as adolescents should have access to the full range of
contraceptives, including long-acting reversible contraceptive methods, they
should be able to decline and discontinue any method on their own, without
barriers. A reproductive justice framework for contraceptive counseling and
access is essential to providing equitable health care, accessing and having
coverage for contraceptive methods, and resisting potential coercion by health
care providers. Successful programs that resulted in measurable changes in
adolescent contraceptive practices and sexual behavior have been described, but
not implemented uniformly nor supported by policy improvements. More research is
needed to determine which programs are most effective and which programs do not
work. Continued efforts are integral to further advance positive trends.
PMID- 28426616
TI - Committee Opinion No. 700 Summary: Methods for Estimating the Due Date.
AB - Accurate dating of pregnancy is important to improve outcomes and is a research
and public health imperative. As soon as data from the last menstrual period, the
first accurate ultrasound examination, or both are obtained, the gestational age
and the estimated due date (EDD) should be determined, discussed with the
patient, and documented clearly in the medical record. Subsequent changes to the
EDD should be reserved for rare circumstances, discussed with the patient, and
documented clearly in the medical record. A pregnancy without an ultrasound
examination that confirms or revises the EDD before 22 0/7 weeks of gestational
age should be considered suboptimally dated. When determined from the methods
outlined in this document for estimating the due date, gestational age at
delivery represents the best obstetric estimate for the purpose of clinical care
and should be recorded on the birth certificate. For the purposes of research and
surveillance, the best obstetric estimate, rather than estimates based on the
last menstrual period alone, should be used as the measure for gestational age.
PMID- 28426617
TI - Clinical Updates in Women's Health Care Summary: Arrhythmias: Primary and
Preventive Care Review.
AB - Obstetrician-gynecologists often are the sole providers of health care to female
patients. Because cardiovascular disease is the leading cause of death in women
in the United States, obstetrician- gynecologists must be aware of the risk
factors, symptoms, and signs of cardiovascular disease and arrhythmia.
Furthermore, they must be prepared to identify and treat common types of
arrhythmia in this population and refer patients to cardiology for specialized
care. Understanding the role of pregnancy among women with arrhythmia is
critically important to optimize both maternal and fetal outcomes. This monograph
discusses the cardiac conduction system and addresses the assessment, diagnosis,
and treatment of both pregnant and nonpregnant patients with heart rhythm
disorders.
PMID- 28426618
TI - Practice Bulletin No 178: Shoulder Dystocia.
PMID- 28426619
TI - Committee Opinion No. 698: Hormone Therapy in Primary Ovarian Insufficiency.
AB - Primary ovarian insufficiency describes a spectrum of declining ovarian function
and reduced fecundity due to a premature decrease in initial follicle number, an
increase in follicle destruction, or poor follicular response to gonadotropins.
The sequelae of primary ovarian insufficiency include vasomotor symptoms,
urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and
increased all-cause mortality. In women with primary ovarian insufficiency,
systemic hormone therapy (HT) is an effective approach to treat the symptoms of
hypoestrogenism and mitigate long-term health risks if there are no
contraindications to treatment. Hormone therapy is indicated to reduce the risk
of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve
the quality of life of women with primary ovarian insufficiency. Although
exogenous estrogen replacement is recommended for women with primary ovarian
insufficiency, data comparing various hormonal regimens for disease prevention,
symptom amelioration, and safety are lacking in this population. As a first-line
approach, HT (either orally or transdermally) that achieves replacement levels of
estrogen is recommended. Combined hormonal contraceptives prevent ovulation and
pregnancy more reliably than HT; despite only modest odds of spontaneous
pregnancy in women with primary ovarian insufficiency, this is a critical
consideration for those who deem pregnancy prevention a priority. Treatment for
all women with primary ovarian insufficiency should continue until the average
age of natural menopause is reached (age 50-51 years). Finally, considering the
challenges that adolescents and young women may face in coping with the physical,
reproductive, and social effects of primary ovarian insufficiency, comprehensive
longitudinal management of this condition is essential.
PMID- 28426620
TI - Committee Opinion No 699: Adolescent Pregnancy, Contraception, and Sexual
Activity.
AB - In 2015, the birth rate among U.S. adolescents and young adults (aged 15-19
years) reached a historic low at 22.3 per 1,000 women. Despite positive trends,
the United States continues to have the highest adolescent pregnancy rate among
industrialized countries with data. Racial and ethnic disparities in adolescent
pregnancy rates continue to exist, as do state-based differences in pregnancy,
birth, and abortion rates. The American College of Obstetricians and
Gynecologists supports access for adolescents to all contraceptive methods
approved by the U.S. Food and Drug Administration. In the absence of
contraindications, patient choice should be the principal factor in prescribing
one method of contraception over another. Dual method use-the use of condoms in
combination with more effective contraceptive methods to protect against sexually
transmitted infections and unwanted pregnancy-is the ideal contraceptive practice
for adolescents. Just as adolescents should have access to the full range of
contraceptives, including long-acting reversible contraceptive methods, they
should be able to decline and discontinue any method on their own, without
barriers. A reproductive justice framework for contraceptive counseling and
access is essential to providing equitable health care, accessing and having
coverage for contraceptive methods, and resisting potential coercion by health
care providers. Successful programs that resulted in measurable changes in
adolescent contraceptive practices and sexual behavior have been described, but
not implemented uniformly nor supported by policy improvements. More research is
needed to determine which programs are most effective and which programs do not
work. Continued efforts are integral to further advance positive trends.
PMID- 28426621
TI - Committee Opinion No 700: Methods for Estimating the Due Date.
AB - Accurate dating of pregnancy is important to improve outcomes and is a research
and public health imperative. As soon as data from the last menstrual period, the
first accurate ultrasound examination, or both are obtained, the gestational age
and the estimated due date (EDD) should be determined, discussed with the
patient, and documented clearly in the medical record. Subsequent changes to the
EDD should be reserved for rare circumstances, discussed with the patient, and
documented clearly in the medical record. A pregnancy without an ultrasound
examination that confirms or revises the EDD before 22 0/7 weeks of gestational
age should be considered suboptimally dated. When determined from the methods
outlined in this document for estimating the due date, gestational age at
delivery represents the best obstetric estimate for the purpose of clinical care
and should be recorded on the birth certificate. For the purposes of research and
surveillance, the best obstetric estimate, rather than estimates based on the
last menstrual period alone, should be used as the measure for gestational age.
PMID- 28426622
TI - CHANGES IN CENTRAL CHOROIDAL THICKNESS AFTER TREATMENT OF DIABETIC MACULAR EDEMA
WITH INTRAVITREAL BEVACIZUMAB CORRELATION WITH CENTRAL MACULAR THICKNESS AND BEST
CORRECTED VISUAL ACUITY.
AB - PURPOSE: To assess the effect of intravitreal injection of bevacizumab on central
choroidal thickness (CCT) and its relationship with central macular thickness
(CMT) and best-corrected visual acuity (BCVA) changes in eyes with center
involving diabetic macular edema. METHODS: This prospective interventional case
series included 20 eyes of 20 patients with center-involving diabetic macular
edema naive to treatment. The BCVA assessment, complete eye examination, enhanced
depth optical coherence tomography, and fluorescein angiography were performed at
baseline followed by 3 monthly intravitreal injection of bevacizumab. The treated
eyes underwent BCVA evaluation and enhanced depth optical coherence tomography at
Months 1, 2, 3, and 6 after the first injection. Change of the CCT was the
primary outcome measure. Secondary outcome measures included BCVA and CMT changes
and their relationship with CCT changes. RESULTS: Mean age of patients was 63.1
+/- 8.0 (range, 52-75) years. Mean baseline CCT was 265 +/- 79 MUm, which reduced
to 251 +/- 81 MUm and 232 +/- 82 MUm at Months 3 and 6, respectively (P < 0.001).
Corresponding values for CMT were 470 +/- 107 MUm, 392 +/- 104 MUm, and 324 +/-
122 MUm, respectively (P < 0.001). The BCVA improved from 20/60 at baseline to
20/50 at Month 3 and 20/40 at Month 6 (P = 0.007). Each 1 MUm decrease in CCT was
associated with 2.74 MUm reduction in CMT and 0.1 Early Treatment Diabetic
Retinopathy Study letter score improvement in BCVA (P < 0.001 and P = 0.001,
respectively). CONCLUSION: After treatment of diabetic macular edema with
intravitreal injection of bevacizumab, CCT decreased and this reduction
significantly correlated with CMT reduction and vision improvement.
PMID- 28426623
TI - INTRAVITREAL DEXAMETHASONE IMPLANTATION IN PATIENTS WITH DIFFERENT MORPHOLOGICAL
DIABETIC MACULAR EDEMA HAVING INSUFFICIENT RESPONSE TO RANIBIZUMAB.
AB - PURPOSE: To evaluate the effectiveness of a single intravitreal injection of
dexamethasone implant in resistant diabetic macular edema that have different
morphological types. METHODS: In this retrospective study, 31 patients (35 eyes)
with persistent diabetic macular edema, who underwent a single injection of
dexamethasone implant, were evaluated. Diabetic macular edema was classified into
three types: diffuse retinal thickening (n = 10), cystoid macular edema (n = 13),
and serous retinal detachment (n = 12). Primary outcome measures were best
corrected visual acuity, and central macular thickness. RESULTS: The three
subgroups were similar in terms of age and gender (P > 0.05). Total duration of
diabetes was significantly less in the serous retinal detachment subgroup (P =
0.01). There were no differences in the best corrected visual acuity between the
three subgroups until the sixth month. However, the best corrected visual acuity
was significantly better in the diffuse retinal thickness subgroup at the sixth
month (P = 0.008). Regarding the central macular thickness values, it was
statistically better in serous retinal detachment than in diffuse retinal
thickening and cystoid macular edema subgroups till the sixth month (P = 0.001).
However, at the sixth month, there was not any statistical difference between
subgroups regarding central macular thickness values. Antiglaucomatous agents
were required in 4 (11.4%) patients throughout the study. CONCLUSION: Treatment
algorithms should differ according to the morphology of diabetic macular edema;
however, more data is needed to give specific recommendations.
PMID- 28426624
TI - A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROL PILOT STUDY OF EPLERENONE FOR THE
TREATMENT OF CENTRAL SEROUS CHORIORETINOPATHY (ECSELSIOR).
AB - PURPOSE: To evaluate the safety and effects of oral eplerenone in chronic central
serous chorioretinopathy. METHODS: Prospective, randomized, double-blind, placebo
control study at a tertiary referral academic private practice. For a diagnosis
of chronic central serous chorioretinopathy, patients must have had at least 3
months clinical follow-up demonstrating persistent symptoms, subfoveal fluid on
spectral-domain optical coherence tomography, and <50% reduction in fluid
thickness. Patients were randomized 2:1 (treatment:placebo) to receive eplerenone
(25 mg daily for 1 week, then up to 50 mg daily for 8 weeks) or placebo once
daily. RESULTS: Fifteen patients completed the study. Ten patients (15 eyes) were
randomized into the eplerenone treatment arm, while the remaining 5 patients (6
eyes) received placebo. After 9 weeks of eplerenone therapy, mean logarithm of
the minimal angle of resolution visual acuity improved from 0.394 (Snellen
equivalent: 20/50) to 0.330 (20/43, P = 0.04). In the placebo group, the mean
logarithm of the minimal angle of resolution visual acuity slightly decreased
from 0.313 (20/41) to 0.342 (20/44) during the same period (P = 0.21). With
respect to anatomic changes, mean maximal subretinal fluid height in the
eplerenone group improved from 139.3 MUm at baseline to 51.8 MUm (P = 0.02), mean
subfoveal fluid height improved from 121.4 MUm to 29.4 MUm (P = 0.01), and mean
central subfield thickness improved from 366.2 MUm to 283.7 MUm (P = 0.02). In
comparison with the placebo group, mean maximal subretinal fluid height worsened
from 135.9 MUm to 172.3 MUm (P = 0.32), mean subfoveal fluid height worsened from
92.1 MUm to 134.0 MUm (P = 0.54), and mean central subfield thickness worsened
from 345.0 MUm to 380.0 MUm (P = 0.37). No patients in either group experienced
serious adverse events to result in treatment discontinuation. CONCLUSION: These
findings suggest that oral eplerenone therapy is safe and potentially effective
in the treatment of chronic central serous chorioretinopathy with persistent
subretinal fluid.
PMID- 28426625
TI - Intraoperative Optical Coherence Tomography-Assisted Chorioretinal Biopsy in the
DISCOVER Study.
PMID- 28426626
TI - PARAPAPILLARY GAMMA AND DELTA ZONES IN HIGH MYOPIA.
AB - PURPOSE: To examine parapapillary zones gamma and delta in highly myopic eyes.
METHODS: The retrospective observational study included patients attending the
Tokyo high myopia clinics. Fundus photographs were morphometrically examined.
RESULTS: The study population included 600 eyes (304 individuals) with a mean age
of 62.7 +/- 14.3 years (range: 13-90 years) and mean axial length of 29.6 +/- 2.2
mm (range: 23.2-35.4 mm). In multivariate analysis (regression coefficient
r:0.90), larger horizontal gamma zone diameter was correlated with wider delta
zone diameter (P < 0.001; standardized regression coefficient beta: 0.81), higher
ratio of vertical-to-horizontal disk diameter (P < 0.001; beta: 0.10), shorter
fovea-outer gamma zone border distance (P < 0.001; beta: -0.19), longer disk
fovea distance (P < 0.001; beta: 0.18), and higher count of chorioretinal
atrophic lesions (P < 0.001; beta: 0.07). Longer horizontal delta zone width was
correlated with longer horizontal gamma zone diameter (P < 0.001; beta: 1.00),
longer horizontal disk diameter (P < 0.001; beta: 0.15), shorter disk-fovea
distance (P < 0.001; beta: -0.19), longer fovea-outer gamma zone border distance
(P < 0.001; beta: 0.19), and smaller diameter of the largest chorioretinal lesion
(P = 0.03; beta: -0.04). Longer width of both zones together was associated with
longer horizontal disk diameter (P < 0.001; beta: 0.31), higher ratio of vertical
to-horizontal disk diameter (P = 0.001; beta: 0.18), longer disk-fovea distance
(P < 0.001; beta: 0.19), shorter fovea-outer gamma zone border distance (P <
0.001; beta: -0.18), higher number of chorioretinal lesions (P < 0.001; beta:
0.30), and longer vertical distance between the superior and inferior temporal
arterial arcade (P = 0.001; beta: 0.13). CONCLUSION: Larger gamma and delta zones
were correlated with larger optic disk and more marked vertical optic disk
rotation, longer disk-fovea distance, higher number of chorioretinal lesions, and
longer temporal vascular arcade diameter. Parapapillary gamma and delta zones may
develop before chorioretinal lesions develop and enlarge.
PMID- 28426627
TI - High Visual Acuity Retinal Prosthesis: Understanding Limitations and Advancements
Toward Functional Prosthetic Vision.
PMID- 28426629
TI - Correspondence.
PMID- 28426628
TI - OCULAR HYPERTENSION AND GLAUCOMA FOLLOWING VITRECTOMY: A Systematic Review.
AB - PURPOSE: Pars plana vitrectomy has been reported to increase the risk of ocular
hypertension and open-angle glaucoma. The authors conducted a systematic review
of randomized and nonrandomized studies to compare the incidence of open-angle
glaucoma and ocular hypertension in vitrectomized versus nonvitrectomized eyes.
METHODS: A literature search was performed using MEDLINE and EMBASE until August
2016. Data on ocular hypertension and open-angle glaucoma incidence and mean
intraocular pressure after at least 1 year were pooled using random-effects
metaanalysis models. Because only nonrandomized studies were retrieved, ROBINS-I
tool was used to assess risk of bias in the review. RESULTS: Seven included
studies had a paired design to compare the outcomes of vitrectomized versus
fellow eyes, with mean follow-up of least 12 months. Four studies (851 patients)
provided data on open-angle glaucoma: incidence in vitrectomized versus non
vitrectomized eyes was 7.8% and 4.8%, respectively, yielding a metaanalytic odds
ratio of 1.67 (95% CI: 1.08-2.57). Six studies (1,060 patients) reported on the
occurrence of ocular hypertension, which was 5.8% in vitrectomized eyes versus
3.1% in fellow eyes (odds ratio: 2.03, 95% CI: 0.97-4.22), without significant
differences in the mean postoperative intraocular pressure (mean difference 0.31
mmHg, 95% CI: -0.26 to 0.89). CONCLUSION: Although the review found increased
risk of open-angle glaucoma with pars plana vitrectomy, the studies were
heterogenous or inconsistent regarding ocular hypertension and intraocular
pressure increase. Larger studies should be conducted in homogenous cohorts of
patients undergoing macular surgery, excluding complex conditions such as retinal
detachment or diabetic retinopathy.
PMID- 28426630
TI - OUTER NUCLEAR LAYER THINNING IN PACHYCHOROID PIGMENT EPITHELIOPATHY.
AB - PURPOSE: To compare the average thicknesses of central inner retinal layers in
eyes with pachychoroid pigment epitheliopathy (PPE), with uncomplicated
pachychoroid (UCP), and of healthy subjects. METHODS: Medical records of patients
with PPE and UCP were retrospectively reviewed. Twenty-nine eyes with foveal PPE,
30 eyes with UCP, and 29 eyes of healthy subjects were included. Spectral-domain
optical coherence tomography with enhanced depth imaging was used for all optical
coherence tomography scans. Mean central inner retinal layer thicknesses were
measured in 1-mm-diameter circle with Spectralis automated segmentation software
and compared between groups. RESULTS: The outer nuclear layer (ONL) and the sum
of the outer plexiform layer and ONL were significantly thinner in the PPE group
than the UCP and control groups (ONL: P < 0.001, P < 0.001; outer plexiform layer
+ ONL: P = 0.002, P = 0.002, respectively). There was no significant difference
between groups regarding thickness of the outer plexiform layer and other inner
retinal layers. Eyes with UCP and normal eyes did not differ. CONCLUSION: The ONL
is thinner in eyes with PPE. The degenerative process of pachychoroid spectrum
diseases may begin with retinal pigment epithelium alterations before subretinal
fluid accumulation. The PPE lesions, commonly seen above pachyvessels, may be an
indicator of photoreceptor apoptosis.
PMID- 28426632
TI - Intraoperative Use of Microscope-Integrated Optical Coherence Tomography for
Subretinal Gene Therapy Delivery.
PMID- 28426631
TI - DIRECTIONAL CHANGES IN TISSUE REFLECTIVITY MAY INFLUENCE FLOW DETECTION ON
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB - PURPOSE: To determine if directional or anatomical changes in tissue reflectivity
of Henle fiber layer (HFL) may influence flow detection on optical coherence
tomography angiography (OCT-A). METHODS: Cross-sectional analysis of consecutive
cases undergoing OCT-A. Directional changes in visualization of HFL were either
produced manually by moving the beam entrance within the pupil or observed
occurring naturally because of tilting of the OCT line-scan within a myopic
staphyloma. Areas of enhanced HFL visualization were identified on cross
sectional and en face structural OCT scans. Visualization of OCT-A flow within
the superficial and the deep capillary plexuses were compared in areas with and
without enhanced HFL reflectivity. RESULTS: Fifteen eyes from 9 patients were
included, with a mean age of 49.6 +/- 17.9 years. On OCT-A, retinal areas with
enhanced HFL reflectivity produced manually or by scan tilting within myopic
staphylomas showed no changes in the superficial capillary plexus flow. However,
deep capillary plexus flow was altered by variable projection of the superficial
flow onto the deeper retinal layers. CONCLUSION: Directional changes in HFL
reflectivity can alter the detection of deep capillary plexus flow imaged with
OCT-A by influencing the projection of superficial flow onto the deeper retinal
layers. We recommend that clinicians minimize scan tilting during scan
acquisition and be aware of this phenomenon in eyes with posterior staphyloma.
PMID- 28426633
TI - Reply.
PMID- 28426636
TI - Use of Mindfulness in Coping With Incivility.
PMID- 28426635
TI - A Life Well Lived: A Tribute to Dr Kathleen T. Heinrich.
PMID- 28426637
TI - Creating Web Sites in Nursing Education.
PMID- 28426638
TI - Decreased Central Nervous System Grey Matter Volume (GMV) in Smokers Affects
Cognitive Abilities: A Systematic Review.
AB - Although cigarette smoking is a leading cause of preventable mortality, tobacco
is consumed by approximately 22% of the adult population worldwide. Smoking is
also a risk factor for cardiovascular disease, affects brain processing, and is a
recognized risk factor for Alzheimer disease (AD). Tobacco toxins (e.g., nicotine
at high levels) inhaled in smoke may cause disorders resulting in preclinical
brain changes. Researchers suggest that there are differences in brain volume
between smokers and non-smokers. This review examines these differences in brain
grey matter volume (GMV). In March/April 2015, MedLine, Embase, and PsycINFO were
searched using the terms: "grey matter" AND "voxel-based" AND "smoking" AND
"cigarette". The 4 studies analyzed found brain GMV decreases in smokers compared
to non-smokers. Furthermore, sex-specific differences were found; while the
thalamus and cerebellum were affected in both sexes, decreased GMV in the
olfactory gyrus was found only in male smokers. Age-group differences were also
found, and these may suggest pre-existing abnormalities that lead to nicotine
dependence in younger individuals. Only 1 study found a positive correlation
between number of pack-years smoked and GMV. Smoking decreases GMV in most brain
areas. This decrease may be responsible for the cognitive impairment and
difficulties with emotional regulation found in smokers compared with non
smokers.
PMID- 28426639
TI - Restaurant Food Allergy Practices - Six Selected Sites, United States, 2014.
AB - Food allergies affect an estimated 15 million persons in the United States (1),
and are responsible for approximately 30,000 emergency department visits and 150
200 deaths each year (2). Nearly half of reported fatal food allergy reactions
over a 13-year period were caused by food from a restaurant or other food service
establishment (3). To ascertain the prevalence of food allergy training, training
topics, and practices related to food allergies, CDC's Environmental Health
Specialists Network (EHS-Net), a collaborative forum of federal agencies and
state and local health departments with six sites, interviewed personnel at 278
restaurants. Fewer than half of the 277 restaurant managers (44.4%), 211 food
workers (40.8%), and 156 servers (33.3%) interviewed reported receiving food
allergy training. Among those who reported receiving training, topics commonly
included the major food allergens and what to do if a customer has a food
allergy. Although most restaurants had ingredient lists for at least some menu
items, few had separate equipment or areas designated for the preparation of
allergen-free food. Restaurants can reduce the risk for allergic reactions among
patrons by providing food allergy training for personnel and ingredient lists for
all menu items and by dedicating equipment and areas specifically for preparing
allergen-free food.
PMID- 28426640
TI - Announcement: Sleep Awareness Week, April 23-29, 2017.
AB - Sleep Awareness Week, the National Sleep Foundation's annual campaign to educate
the public about the importance of sleep in health and safety, will be observed
April 23-29, 2017. The amount of sleep a person needs changes with age. Adults
need >=7 hours each night to promote optimal health and well-being (1); children
and adolescents require even more sleep. Sleep needs decrease from 12-16 hours of
sleep per 24 hours (including naps) for infants aged 4-12 months to 8-10 hours of
sleep for teenagers aged 13-18 years (2). Children who regularly sleep less than
the recommended amount are more likely to have behavior and learning problems,
physical and mental health conditions such as obesity, diabetes, depression, or
injuries (2). A regular bedtime routine can help children get adequate sleep. The
American Academy of Pediatrics provides advice for parents at
https://www.healthychildren.org/English/healthy-living/sleep/. Additional details
about how much sleep is recommended across a lifespan is available at
https://www.cdc.gov/sleep/about_sleep/how_much_sleep.html.
PMID- 28426641
TI - Notes from the Field: Powassan Virus Disease in an Infant - Connecticut, 2016.
PMID- 28426642
TI - QuickStats: Number of Deaths from 10 Leading Causes,* by Sex - National Vital
Statistics System, United States, 2015.
AB - In 2015, a total of 1,339,226 deaths among females and 1,373,404 deaths among
males occurred. Heart disease and cancer were the top two causes of death for
both females and males; other leading causes varied in rank by sex. The 10
leading causes of death accounted for approximately three-quarters of all deaths.
PMID- 28426643
TI - Incidence and Trends of Infections with Pathogens Transmitted Commonly Through
Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on
Surveillance - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites,
2013-2016.
AB - Foodborne diseases represent a substantial public health concern in the United
States. CDC's Foodborne Diseases Active Surveillance Network (FoodNet) monitors
cases reported from 10 U.S. sites* of laboratory-diagnosed infections caused by
nine enteric pathogens commonly transmitted through food. This report describes
preliminary surveillance data for 2016 on the nine pathogens and changes in
incidences compared with 2013-2015. In 2016, FoodNet identified 24,029
infections, 5,512 hospitalizations, and 98 deaths caused by these pathogens. The
use of culture-independent diagnostic tests (CIDTs) by clinical laboratories to
detect enteric pathogens has been steadily increasing since FoodNet began
surveying clinical laboratories in 2010 (1). CIDTs complicate the interpretation
of FoodNet surveillance data because pathogen detection could be affected by
changes in health care provider behaviors or laboratory testing practices (2).
Health care providers might be more likely to order CIDTs because these tests are
quicker and easier to use than traditional culture methods, a circumstance that
could increase pathogen detection (3). Similarly, pathogen detection could also
be increasing as clinical laboratories adopt DNA-based syndromic panels, which
include pathogens not often included in routine stool culture (4,5). In addition,
CIDTs do not yield isolates, which public health officials rely on to distinguish
pathogen subtypes, determine antimicrobial resistance, monitor trends, and detect
outbreaks. To obtain isolates for infections identified by CIDTs, laboratories
must perform reflex culture?; if clinical laboratories do not, the burden of
culturing falls to state public health laboratories, which might not be able to
absorb that burden as the adoption of these tests increases (2). Strategies are
needed to preserve access to bacterial isolates for further characterization and
to determine the effect of changing trends in testing practices on surveillance.
PMID- 28426644
TI - Notes from the Field: Varicella Fatality on a Cargo Vessel - Puerto Rico, 2015.
PMID- 28426645
TI - Announcement: World Malaria Day - April 25, 2017.
AB - World Malaria Day is commemorated each year on April 25, the date in 2000 when
leaders of 44 African nations met in Abuja, Nigeria, and committed their
countries to reducing the number of malaria-related deaths. Approximately 90% of
all malaria deaths occur in Africa (1). During the last 15 years, donors have
collectively supported the procurement and distribution of billions of
insecticide-treated bed nets and courses of artemisinin-based combination therapy
globally. These improvements in malaria control are estimated to have saved an
estimated 6.8 million lives, mostly among children aged <5 years. From 2010 to
2015, the World Health Organization (WHO) reported that the estimated number of
malaria deaths worldwide declined by approximately 60%, including a 69% decline
among children aged <5 years (1). This year, as in 2016, the theme of World
Malaria Day is "End Malaria for Good," reflecting the increased interest in and
commitment to eliminating malaria.
PMID- 28426646
TI - Community Mitigation Guidelines to Prevent Pandemic Influenza - United States,
2017.
AB - When a novel influenza A virus with pandemic potential emerges, nonpharmaceutical
interventions (NPIs) often are the most readily available interventions to help
slow transmission of the virus in communities, which is especially important
before a pandemic vaccine becomes widely available. NPIs, also known as community
mitigation measures, are actions that persons and communities can take to help
slow the spread of respiratory virus infections, including seasonal and pandemic
influenza viruses.These guidelines replace the 2007 Interim Pre-pandemic Planning
Guidance: Community Strategy for Pandemic Influenza Mitigation in the United
States - Early, Targeted, Layered Use of Nonpharmaceutical Interventions
(https://stacks.cdc.gov/view/cdc/11425). Several elements remain unchanged from
the 2007 guidance, which described recommended NPIs and the supporting rationale
and key concepts for the use of these interventions during influenza pandemics.
NPIs can be phased in, or layered, on the basis of pandemic severity and local
transmission patterns over time. Categories of NPIs include personal protective
measures for everyday use (e.g., voluntary home isolation of ill persons,
respiratory etiquette, and hand hygiene); personal protective measures reserved
for influenza pandemics (e.g., voluntary home quarantine of exposed household
members and use of face masks in community settings when ill); community measures
aimed at increasing social distancing (e.g., school closures and dismissals,
social distancing in workplaces, and postponing or cancelling mass gatherings);
and environmental measures (e.g., routine cleaning of frequently touched
surfaces).Several new elements have been incorporated into the 2017 guidelines.
First, to support updated recommendations on the use of NPIs, the latest
scientific evidence available since the influenza A (H1N1)pdm09 pandemic has been
added. Second, a summary of lessons learned from the 2009 H1N1 pandemic response
is presented to underscore the importance of broad and flexible prepandemic
planning. Third, a new section on community engagement has been included to
highlight that the timely and effective use of NPIs depends on community
acceptance and active participation. Fourth, to provide new or updated pandemic
assessment and planning tools, the novel influenza virus pandemic intervals tool,
the Influenza Risk Assessment Tool, the Pandemic Severity Assessment Framework,
and a set of prepandemic planning scenarios are described. Finally, to facilitate
implementation of the updated guidelines and to assist states and localities with
prepandemic planning and decision-making, this report links to six supplemental
prepandemic NPI planning guides for different community settings that are
available online (https://www.cdc.gov/nonpharmaceutical-interventions).
PMID- 28426647
TI - Association of prenatal urinary phthalate metabolite concentrations and childhood
BMI and obesity.
AB - BackgroundAlthough experiments in animals suggest that phthalates may have
obesogenic effects, studies on prenatal exposure in children show inconsistent
results.MethodsWe measured urinary concentrations of 11 phthalate metabolites
collected twice during pregnancy from mothers participating in the Center for the
Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study
(N=345). Height, weight, waist circumference, and percent body fat were assessed
in their children between 5 and 12 years of age. We used generalized estimating
equations to examine associations at each age and tested for interaction by
sex.ResultsMetabolites of diethyl phthalate (DEP), di-n-butyl phthalate (DBP),
butyl benzyl phthalate, and di(2-ethylhexyl) phthalate (DEHP) were positively
associated with BMI z-score, waist circumference z-score, and percent body fat at
multiple ages. At age 12, we observed increased odds of being overweight/obese
with each doubling of prenatal concentrations of DEP (odds ratio=1.3; 95%
confidence intervals: 1.1, 1.4), DBP (1.2; 1.0, 1.4), and DEHP (1.3; 1.0, 1.6)
metabolites. Results were similar in boys and girls except for DBP metabolites
and the non-specific metabolite mono-(3-carboxypropyl) phthalate, which showed
positive associations only in boys.ConclusionIn utero exposure to certain
phthalates is associated with increased BMI and risk for overweight/obesity in
childhood.
PMID- 28426648
TI - Pregnancy swimming causes short- and long-term neuroprotection against hypoxia
ischemia in very immature rats.
AB - BackgroundHypoxia-ischemia (HI) is a major cause of neurological damage in
preterm newborn. Swimming during pregnancy alters the offspring's brain
development. We tested the effects of swimming during pregnancy in the very
immature rat brain.MethodsFemale Wistar rats (n=12) were assigned to the
sedentary (SE, n=6) or the swimming (SW, n=6) group. From gestational day 0 (GD0)
to GD21 the rats in the SW group were made to swim for 20 min/day. HI on
postnatal day (PND) 3 rats caused sensorimotor and cognitive impairments. Animals
were distributed into SE sham (SESH), sedentary HIP3 (SEHI), swimming sham
(SWSH), and swimming HIP3 (SWHI) groups. At PND4 and PND5, Na+/K+-ATPase activity
and brain-derived neurotrophic factor (BDNF) levels were assessed. During
lactation and adulthood, neurological reflexes, sensorimotor, anxiety-related,
and cognitive evaluations were made, followed by histological assessment at
PND60.ResultsAt early stages, swimming caused an increase in hippocampal BDNF
levels and in the maintenance of Na+/K+-ATPase function in the SWHI group. The
SWHI group showed smaller lesions and the preservation of white matter tracts.
SEHI animals showed a delay in reflex maturation, which was reverted in the SWHI
group. HIP3 induced spatial memory deficits and hypomyelination in SEHI rats,
which was reverted in the SWHI group.ConclusionSwimming during pregnancy
neuroprotected the brains against HI in very immature neonatal rats.
PMID- 28426649
TI - The importance of appropriate initial bacterial colonization of the intestine in
newborn, child, and adult health.
AB - The fetus does not reside in a sterile intrauterine environment and is exposed to
commensal bacteria from the maternal gut/blood stream that cross the placenta and
enter the amniotic fluid. This intestinal exposure to colonizing bacteria
continues at birth and during the first year of life and has a profound influence
on lifelong health. Why is this important? Intestinal crosstalk with colonizing
bacteria in the developing intestine affects the infant's adaptation to
extrauterine life (immune homeostasis) and provides protection against disease
expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing
intestinal bacteria are critical to the normal development of host defense.
Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section
delivery, use of perinatal antibiotics, or premature delivery may adversely
affect the gut development of host defense and predispose to inflammation rather
than to homeostasis, leading to increased susceptibility to disease later in
life. Babies born by cesarean section have a higher incidence of allergy, type 1
diabetes, and obesity. Infants given repeated antibiotic regimens during the
first year of life are more likely to have asthma as adolescents. This research
breakthrough helps to explain the shift in disease paradigms from infections to
immune-mediated in children from developed countries. This review will develop
this research breakthrough.
PMID- 28426650
TI - Neural injury markers in intrauterine growth restriction and their relation to
perinatal outcomes.
AB - BACKGROUNDThe aims of this study were to (i) compare the concentrations of two
neural injury markers, S100B protein and neuron-specific enolase (NSE), in
intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate
growth-for-gestational-age (AGA), and (ii) investigate potential relationships
between concentrations of these markers, Doppler abnormalities, and adverse
perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative,
prospective study among Spanish Maternal and Child Health Network (Retic SAMID)
hospitals. At inclusion, biometry for estimated fetal weight and feto-placental
Doppler were measured. At the time of delivery, maternal venous blood and fetal
umbilical arterial blood samples were collected. S100B and NSE concentrations
were determined from these samples.RESULTSIn total, 254 pregnancies were
included. Among these, 147 were classified as IUGR and 107 as AGA. There were no
differences between the groups in S100B concentrations. However, levels of NSE in
maternal and umbilical cord serum differed significantly between these groups
(2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR
(P<0.05), respectively). No differences were observed in these neurological
markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough
some variations exist in these neurological markers, they did not correlate with
perinatal or neonatal complications.
PMID- 28426651
TI - Association of candidate gene polymorphisms with clinical subtypes of preterm
birth in a Latin American population.
AB - BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and
morbidity. PTB is often classified according to clinical presentation as follows:
idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and
medically induced (PTB-M). The aim of this study was to evaluate the associations
between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four
single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in
709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB
M. These data were analyzed with a Family-Based Association.ResultsPTB was
nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in
CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were
associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in
CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and
rs610277 in F3 were associated with PTB-M.ConclusionOur study identified
polymorphisms potentially associated with specific clinical subtypes of PTB in
this Latin American population. These results could suggest a specific role of
such genes in the mechanisms involved in each clinical subtype. Further studies
are required to confirm our results and to determine the role of these genes in
the pathophysiology of clinical subtypes.
PMID- 28426653
TI - The evolving schistosomiasis agenda 2007-2017-Why we are moving beyond morbidity
control toward elimination of transmission.
PMID- 28426652
TI - Cheminformatics-aided discovery of small-molecule Protein-Protein Interaction
(PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF
kappaB Ligand (RANKL).
AB - We present an in silico drug discovery pipeline developed and applied for the
identification and virtual screening of small-molecule Protein-Protein
Interaction (PPI) compounds that act as dual inhibitors of TNF and RANKL through
the trimerization interface. The cheminformatics part of the pipeline was
developed by combining structure-based with ligand-based modeling using the
largest available set of known TNF inhibitors in the literature (2481 small
molecules). To facilitate virtual screening, the consensus predictive model was
made freely available at: http://enalos.insilicotox.com/TNFPubChem/. We thus
generated a priority list of nine small molecules as candidates for direct TNF
function inhibition. In vitro evaluation of these compounds led to the selection
of two small molecules that act as potent direct inhibitors of TNF function, with
IC50 values comparable to those of a previously-described direct inhibitor
(SPD304), but with significantly reduced toxicity. These molecules were also
identified as RANKL inhibitors and validated in vitro with respect to this second
functionality. Direct binding of the two compounds was confirmed both for TNF and
RANKL, as well as their ability to inhibit the biologically-active trimer forms.
Molecular dynamics calculations were also carried out for the two small molecules
in each protein to offer additional insight into the interactions that govern TNF
and RANKL complex formation. To our knowledge, these compounds, namely T8 and
T23, constitute the second and third published examples of dual small-molecule
direct function inhibitors of TNF and RANKL, and could serve as lead compounds
for the development of novel treatments for inflammatory and autoimmune diseases.
PMID- 28426654
TI - Mycetoma: A global medical and socio-economic dilemma.
PMID- 28426655
TI - Glycosome biogenesis in trypanosomes and the de novo dilemma.
AB - Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative
agents of lethal diseases threatening millions of people around the world. These
organisms compartmentalize glycolysis in essential, specialized peroxisomes
called glycosomes. Peroxisome proliferation can occur through growth and division
of existing organelles and de novo biogenesis from the endoplasmic reticulum. The
level that each pathway contributes is debated. Current evidence supports the
concerted contribution of both mechanisms in an equilibrium that can vary
depending on environmental conditions and metabolic requirements of the cell.
Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis
and matrix protein import, have been identified in T. brucei. Based on these
findings, it is widely accepted that glycosomes proliferate through growth and
division of existing organelles; however, to our knowledge, a de novo mechanism
of biogenesis has not been directly demonstrated. Here, we review recent findings
that provide support for the existence of an endoplasmic reticulum (ER)-derived
de novo pathway of glycosome biogenesis in T. brucei. Two studies recently
identified PEX13.1, a peroxin involved in matrix protein import, in the ER of
procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been
found in the ER of cells undergoing de novo biogenesis of peroxisomes. In
addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are
important for de novo biogenesis in other eukaryotes. Because glycosomes are
rapidly remodeled via autophagy during life cycle differentiation, de novo
biogenesis could provide a method of restoring glycosome populations following
turnover. Together, the findings we summarize provide support for the hypothesis
that glycosome proliferation occurs through growth and division of pre-existing
organelles and de novo biogenesis of new organelles from the ER and that the
level each mechanism contributes is influenced by glucose availability.
PMID- 28426657
TI - Cystic and alveolar echinococcosis: Successes and continuing challenges.
PMID- 28426656
TI - The role of 'omics' in the quest to eliminate human filariasis.
PMID- 28426658
TI - The PLOS Neglected Tropical Diseases decade.
PMID- 28426659
TI - Three distinct mechanisms of long-distance modulation of gene expression in
yeast.
AB - Recent Hi-C measurements have revealed numerous intra- and inter-chromosomal
interactions in various eukaryotic cells. To what extent these interactions
regulate gene expression is not clear. This question is particularly intriguing
in budding yeast because it has extensive long-distance chromosomal interactions
but few cases of gene regulation over-a-distance. Here, we developed a medium
throughput assay to screen for functional long-distance interactions that affect
the average expression level of a reporter gene as well as its cell-to-cell
variability (noise). We ectopically inserted an insulated MET3 promoter (MET3pr)
flanked by ~1kb invariable sequences into thousands of genomic loci, allowing it
to make contacts with different parts of the genome, and assayed the MET3pr
activity in single cells. Changes of MET3pr activity in this case necessarily
involve mechanisms that function over a distance. MET3pr has similar activities
at most locations. However, at some locations, they deviate from the norm and
exhibit three distinct patterns including low expression / high noise, low
expression / low noise, and high expression / low noise. We provided evidence
that these three patterns of MET3pr expression are caused by Sir2-mediated
silencing, transcriptional interference, and 3D clustering. The clustering also
occurs in the native genome and enhances the transcription of endogenous Met4
targeted genes. Overall, our results demonstrate that a small fraction of long
distance chromosomal interactions can affect gene expression in yeast.
PMID- 28426661
TI - Parasite genomics-Time to think bigger.
PMID- 28426660
TI - Exhaustive search of linear information encoding protein-peptide recognition.
AB - High-throughput in vitro methods have been extensively applied to identify linear
information that encodes peptide recognition. However, these methods are limited
in number of peptides, sequence variation, and length of peptides that can be
explored, and often produce solutions that are not found in the cell. Despite the
large number of methods developed to attempt addressing these issues, the
exhaustive search of linear information encoding protein-peptide recognition has
been so far physically unfeasible. Here, we describe a strategy, called DALEL,
for the exhaustive search of linear sequence information encoded in proteins that
bind to a common partner. We applied DALEL to explore binding specificity of SH3
domains in the budding yeast Saccharomyces cerevisiae. Using only the polypeptide
sequences of SH3 domain binding proteins, we succeeded in identifying the
majority of known SH3 binding sites previously discovered either in vitro or in
vivo. Moreover, we discovered a number of sites with both non-canonical sequences
and distinct properties that may serve ancillary roles in peptide recognition. We
compared DALEL to a variety of state-of-the-art algorithms in the blind
identification of known binding sites of the human Grb2 SH3 domain. We also
benchmarked DALEL on curated biological motifs derived from the ELM database to
evaluate the effect of increasing/decreasing the enrichment of the motifs. Our
strategy can be applied in conjunction with experimental data of proteins
interacting with a common partner to identify binding sites among them. Yet, our
strategy can also be applied to any group of proteins of interest to identify
enriched linear motifs or to exhaustively explore the space of linear information
encoded in a polypeptide sequence. Finally, we have developed a webserver located
at http://michnick.bcm.umontreal.ca/dalel, offering user-friendly interface and
providing different scenarios utilizing DALEL.
PMID- 28426662
TI - PLOS Neglected Tropical Diseases: Ten years of progress in neglected tropical
disease control and elimination ... More or less.
AB - This year PLOS Neglected Tropical Diseases (PLOS NTDs) celebrates its tenth
anniversary following the publication of the first issue in 2007 [1]. When PLOS
NTDs was founded, the framework of the neglected tropical diseases (NTDs) as an
alternative to "other diseases" (as they were then referred to in the Millennium
Development Goals) was just getting started-especially for Africa [2, 3]. In the
decade since, PLOS NTDs has overseen enormous successes in NTD control and
elimination. Here, we want to briefly review the ten year progress made towards
the control or elimination of the diseases now identified by the WHO as NTDs.
Many of the details are highlighted in PLOS NTDs papers cited here, but the
summary information is based on the recently released Global Burden of Disease
(GBD) Study 2015 (also launched with Gates Foundation support) that summarized
past-decade changes in disease prevalence, mortality, or disability rates (from
the years 2005 to 2015) [4-6], as well as the GBD Study 2013 that summarizes
disease prevalence changes over a longer time horizon from 1990 to 2013 [7].
PMID- 28426663
TI - Guinea worm eradication: Progress and challenges- should we beware of the dog?
PMID- 28426664
TI - Taenia solium cysticercosis and taeniosis: Achievements from the past 10 years
and the way forward.
PMID- 28426666
TI - Neglected tropical diseases: A DFID perspective.
PMID- 28426665
TI - Oncodomains: A protein domain-centric framework for analyzing rare variants in
tumor samples.
AB - The fight against cancer is hindered by its highly heterogeneous nature. Genome
wide sequencing studies have shown that individual malignancies contain many
mutations that range from those commonly found in tumor genomes to rare somatic
variants present only in a small fraction of lesions. Such rare somatic variants
dominate the landscape of genomic mutations in cancer, yet efforts to correlate
somatic mutations found in one or few individuals with functional roles have been
largely unsuccessful. Traditional methods for identifying somatic variants that
drive cancer are 'gene-centric' in that they consider only somatic variants
within a particular gene and make no comparison to other similar genes in the
same family that may play a similar role in cancer. In this work, we present
oncodomain hotspots, a new 'domain-centric' method for identifying clusters of
somatic mutations across entire gene families using protein domain models. Our
analysis confirms that our approach creates a framework for leveraging structural
and functional information encapsulated by protein domains into the analysis of
somatic variants in cancer, enabling the assessment of even rare somatic variants
by comparison to similar genes. Our results reveal a vast landscape of somatic
variants that act at the level of domain families altering pathways known to be
involved with cancer such as protein phosphorylation, signaling, gene regulation,
and cell metabolism. Due to oncodomain hotspots' unique ability to assess rare
variants, we expect our method to become an important tool for the analysis of
sequenced tumor genomes, complementing existing methods.
PMID- 28426668
TI - Neglected tropical diseases: A proxy for equitable development and shared
prosperity.
PMID- 28426667
TI - Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a
zebrafish model of spinal muscular atrophy.
AB - Degeneration and loss of lower motor neurons is the major pathological hallmark
of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously
expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved,
feature of SMA is that not all motor neurons are equally affected, with some
populations displaying a robust resistance to the disease. Here, we demonstrate
that selective vulnerability of distinct motor neuron pools arises from
fundamental modifications to their basal molecular profiles. Comparative gene
expression profiling of motor neurons innervating the extensor digitorum longus
(disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis
anterior (vulnerable) muscles in mice revealed that disease susceptibility
correlates strongly with a modified bioenergetic profile. Targeting of identified
bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon
defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein,
phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron
vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic
the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or
treatment with terazosin (an FDA-approved small molecule that binds and activates
Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global
bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor
neuron phenotypes in vivo.
PMID- 28426669
TI - A dynamic genetic-hormonal regulatory network model explains multiple cellular
behaviors of the root apical meristem of Arabidopsis thaliana.
AB - The study of the concerted action of hormones and transcription factors is
fundamental to understand cell differentiation and pattern formation during organ
development. The root apical meristem of Arabidopsis thaliana is a useful model
to address this. It has a stem cell niche near its tip conformed of a quiescent
organizer and stem or initial cells around it, then a proliferation domain
followed by a transition domain, where cells diminish division rate before
transiting to the elongation zone; here, cells grow anisotropically prior to
their final differentiation towards the plant base. A minimal model of the gene
regulatory network that underlies cell-fate specification and patterning at the
root stem cell niche was proposed before. In this study, we update and couple
such network with both the auxin and cytokinin hormone signaling pathways to
address how they collectively give rise to attractors that correspond to the
genetic and hormonal activity profiles that are characteristic of different cell
types along A. thaliana root apical meristem. We used a Boolean model of the
genetic-hormonal regulatory network to integrate known and predicted regulatory
interactions into alternative models. Our analyses show that, after adding some
putative missing interactions, the model includes the necessary and sufficient
components and regulatory interactions to recover attractors characteristic of
the root cell types, including the auxin and cytokinin activity profiles that
correlate with different cellular behaviors along the root apical meristem.
Furthermore, the model predicts the existence of activity configurations that
could correspond to the transition domain. The model also provides a possible
explanation for apparently paradoxical cellular behaviors in the root meristem.
For example, how auxin may induce and at the same time inhibit WOX5 expression.
According to the model proposed here the hormonal regulation of WOX5 might depend
on the cell type. Our results illustrate how non-linear multi-stable qualitative
network models can aid at understanding how transcriptional regulators and
hormonal signaling pathways are dynamically coupled and may underlie both the
acquisition of cell fate and the emergence of hormonal activity profiles that
arise during complex organ development.
PMID- 28426670
TI - Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1)
show modestly enhanced alcohol preference and consumption.
AB - We recently characterized S426A/S430A mutant mice expressing a desensitization
resistant form of the CB1 receptor. These mice display an enhanced response to
endocannabinoids and ?9-THC. In this study, S426A/S430A mutants were used as a
novel model to test whether ethanol consumption, morphine dependence, and reward
for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1.
Using an unlimited-access, two-bottle choice, voluntary drinking paradigm,
S426A/S430A mutants exhibit modestly increased intake and preference for low (6%)
but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice
show similar taste preference for sucrose and quinine, exhibit normal sensitivity
to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol
concentrations following administration of ethanol. S426A/S430A mutants develop
robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg),
and cocaine (10 mg/kg), demonstrating that drug reward is not changed in
S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid
dependent S426A/S430A mutant mice. Although ethanol consumption is modestly
changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to
ethanol and morphine are normal in this model.
PMID- 28426671
TI - Effect of mitochondrially targeted carboxy proxyl nitroxide on Akt-mediated
survival in Daudi cells: Significance of a dual mode of action.
AB - Vicious cycles of mutations and reactive oxygen species (ROS) generation
contribute to cancer progression. The use of antioxidants to inhibit ROS
generation promotes cytostasis by affecting the mutation cycle and ROS-dependent
survival signaling. However, cancer cells select mutations to elevate ROS albeit
maintaining mitochondrial hyperpolarization (Deltapsim), even under hypoxia. From
this perspective, the use of drugs that disrupt both ROS generation and Deltapsim
is a viable anticancer strategy. Hence, we studied the effects of mitochondrially
targeted carboxy proxyl nitroxide (Mito-CP) and a control ten carbon TPP moiety
(Dec-TPP+) in the human Burkitt lymphoma cell line (Daudi) and normal peripheral
blood mononuclear cells under hypoxia and normoxia. We found preferential
localization, Deltapsim and adenosine triphosphate loss, and significant
cytotoxicity by Mito-CP in Daudi cells alone. Interestingly, ROS levels were
decreased and maintained in hypoxic and normoxic cancer cells, respectively, by
Mito-CP but not Dec-TPP+, therefore preventing any adaptive signaling. Moreover,
dual effects on mitochondrial bioenergetics and ROS by Mito-CP curtailed the
cancer survival via Akt inhibition, AMPK-HIF-1alpha activation and promoted
apoptosis via increased BCL2-associated X protein and poly (ADP-ribose)
polymerase expression. This dual mode of action by Mito-CP provides a better
explanation of the application of antioxidants with specific relevance to
cancerous transformation and adaptations in the Daudi cell line.
PMID- 28426672
TI - How to determine if a model is right for neglected tropical disease decision
making.
AB - Mathematical and computational modeling can transform decision making for
neglected tropical diseases (NTDs) if the right model is used for the right
question. Modeling can help better understand and address the complex systems
involved in making decisions for NTD prevention and control. However, all models,
modelers, and modeling are not the same. Thus, decision makers need to better
understand if a particular model actually fits their needs. Here are a series of
questions that a decision maker can ask when determining whether a model is right
for him or her.
PMID- 28426673
TI - Lymph node volume predicts survival but not nodal clearance in Stage IIIA-IIIB
NSCLC.
AB - BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) patients have
poorer survival and local control with mediastinal node (N2) tumor involvement at
resection. Earlier assessment of nodal burden could inform clinical decision
making prior to surgery. This study evaluated the association between clinical
outcomes and lymph node volume before and after neoadjuvant therapy. MATERIALS
AND METHODS: CT imaging of patients with operable LA-NSCLC treated with
chemoradiation and surgical resection was assessed. Clinically involved lymph
node stations were identified by FDG-PET or mediastinoscopy. Locoregional
recurrence (LRR), distant metastasis (DM), progression free survival (PFS) and
overall survival (OS) were analyzed by the Kaplan Meier method, concordance index
and Cox regression. RESULTS: 73 patients with Stage IIIA-IIIB NSCLC treated with
neoadjuvant chemoradiation and surgical resection were identified. The median RT
dose was 54 Gy and all patients received concurrent chemotherapy. Involved lymph
node volume was significantly associated with LRR and OS but not DM on univariate
analysis. Additionally, lymph node volume greater than 10.6 cm3 after the
completion of preoperative chemoradiation was associated with increased LRR
(p<0.001) and decreased OS (p = 0.04). There was no association between nodal
volumes and nodal clearance. CONCLUSION: For patients with LA-NSCLC, large volume
nodal disease post-chemoradiation is associated with increased risk of
locoregional recurrence and decreased survival. Nodal volume can thus be used to
further stratify patients within the heterogeneous Stage IIIA-IIIB population and
potentially guide clinical decision-making.
PMID- 28426674
TI - Tribological investigations of the load, temperature, and time dependence of wear
in sliding contact.
AB - An effort was made to study and characterize the evolution of transient
tribological wear in the presence of sliding contact. Sliding contact is often
characterized experimentally via the standard ASTM D4172 four-ball test, and
these tests were conducted for varying times ranging from 10 seconds to 1 hour,
as well as at varying temperatures and loads. A numerical model was developed to
simulate the evolution of wear in the elastohydrodynamic regime. This model uses
the results of a Monte Carlo study to develop novel empirical equations for wear
rate as a function of asperity height and lubricant thickness; these equations
closely represented the experimental data and successfully modeled the sliding
contact.
PMID- 28426675
TI - Indicators of suboptimal biologic therapy over time in patients with ulcerative
colitis and Crohn's disease in the United States.
AB - This study assessed the occurrence of indicators for suboptimal biologic therapy
among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the
United States (US). Data from a large US claims database (2005-2013) were used to
retrospectively identify patients with diagnosed with either UC or CD who were
new biologic users. Indicators of suboptimal biologic therapy included: dose
escalation during the maintenance phase, discontinuation of the initial biologic,
switch to another biologic within 90 days following the last day of supply of the
initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD
related surgery, UC- or CD-related urgent care, and development of fistula (for
CD only). Kaplan-Meier analyses were used. A total of 1,699 UC and 4,569 CD
patients were included. Among UC patients, 51.1% and 90.9% experienced >=1
indicator of suboptimal biologic therapy within 6 months and 36 months of
biologic therapy initiation, respectively. Among CD patients, 54.3% and 91.4%
experienced >=1 indicator of suboptimal biologic therapy within 6 and 36 months
of biologic therapy initiation, respectively. For both UC and CD patients, the
most frequent indicators of suboptimal biologic therapy were discontinuation,
dose escalation and augmentation. In conclusion, this study found that the
occurrence of suboptimal biologic therapy is common among patients with UC and
CD, with approximately 90% of patients experiencing at least one indicator of
suboptimal biologic therapy within 36 months of biologic treatment initiation.
PMID- 28426676
TI - Economic injury levels for Asian citrus psyllid control in process oranges from
mature trees with high incidence of huanglongbing.
AB - The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the key pest of
citrus wherever it occurs due to its role as vector of huanglongbing (HLB) also
known as citrus greening disease. Insecticidal vector control is considered to be
the primary strategy for HLB management and is typically intense owing to the
severity of this disease. While this approach slows spread and also decreases
severity of HLB once the disease is established, economic viability of
increasingly frequent sprays is uncertain. Lacking until now were studies
evaluating the optimum frequency of insecticide applications to mature trees
during the growing season under conditions of high HLB incidence. We related
different degrees of insecticide control with ACP abundance and ultimately, with
HLB-associated yield losses in two four-year replicated experiments conducted in
commercial groves of mature orange trees under high HLB incidence. Decisions on
insecticide applications directed at ACP were made by project managers and
confined to designated plots according to experimental design. All operational
costs as well as production benefits were taken into account for economic
analysis. The relationship between management costs, ACP abundance and HLB
associated economic losses based on current prices for process oranges was used
to determine the optimum frequency and timing for insecticide applications during
the growing season. Trees under the most intensive insecticidal control harbored
fewest ACP resulting in greatest yields. The relationship between vector
densities and yield loss was significant but differed between the two test
orchards, possibly due to varying initial HLB infection levels, ACP populations
or cultivar response. Based on these relationships, treatment thresholds during
the growing season were obtained as a function of application costs, juice market
prices and ACP densities. A conservative threshold for mature trees with high
incidence of HLB would help maintain economic viability by reducing excessive
insecticide sprays, thereby leaving more room for non-aggressive management tools
such as biological control.
PMID- 28426677
TI - Information ranks highest: Expectations of female adolescents with a rare genital
malformation towards health care services.
AB - BACKGROUND: Access to highly specialized health care services and support to meet
the patient's specific needs is critical for health outcome, especially during
age-related transitions within the health care system such as with adolescents
entering adult medicine. Being affected by an orphan disease complicates the
situation in several important respects. Long distances to dedicated institutions
and scarcity of knowledge, even among medical doctors, may present major
obstacles for proper access to health care services and health chances. This
study is part of the BMBF funded TransCareO project examining in a mixed-method
design health care provisional deficits, preferences, and barriers in health care
access as perceived by female adolescents affected by the Mayer-Rokitansky-Kuster
Hauser syndrome (MRKHS), a rare (orphan) genital malformation. METHODS: Prior to
a communicative validation workshop, critical elements of MRKHS related care and
support (items) were identified in interviews with MRKHS patients. During the
subsequent workshop, 87 persons involved in health care and support for MRKHS
were asked to rate the items using a 7-point Likert scale (7, strongly agree; 1,
strongly disagree) as to 1) the elements' potential importance (i.e., health care
expected to be "best practice", or priority) and 2) the presently experienced
care. A gap score between the two was computed highlighting fields of action.
Items were arranged into ten separate questionnaires representing domains of care
and support (e.g., online-portal, patient participation). Within each domain,
several items addressed various aspects of "information" and "access". Here, we
present the outcome of items' evaluation by patients (attended, NPAT = 35;
respondents, NRESP = 19). RESULTS: Highest priority scores occurred for domains
"Online-Portal", "Patient participation", and "Tailored informational offers",
characterizing them as extremely important for the perception as best practice.
Highest gap scores yielded domains "Tailored informational offers", reflecting
perceived lack of disease-related information for affected persons, medical
experts, and health insurance companies, "Online-Portal" (with limited
information available on specialist clinics and specialized doctors), and
regarding insufficient support offers (e.g., in school and occupational
settings). Conversely, lowest gap scores were found with group offers for MRKHS
patients ("Transition programs") and MRKHS self-help days ("Patient
participation"), suggesting satisfaction or good solutions in place. DISCUSSION:
The importance assigned to disease-related information indicates that
informational deficits are perceived by patients as barriers, hindering proper
access to health care, especially in an orphan disease. Access to health-related
information plays a role for all persons seeking help and care. However, the
overwhelmingly high scores attributed to these elements in the context of an
orphan disease reveal that here improved information policies are crucial,
demanding for institutionalized solutions supported by the health care system.
IMPLICATIONS FOR PRACTICE: The disparity between experience of care and
attribution as best practice detected describes areas of action in all domains
involved, highlighting information related fields. New concepts and structures
for health care in orphan diseases could draw upon these patient-oriented results
a) regarding orphan-disease specific elements demanding institutionalized
reimbursement, b) essential elements for center care and corresponding networks,
and c) elements reflecting patients' participation in the conception of centers
for rare diseases.
PMID- 28426678
TI - Nutrition education improves dietary diversity of children 6-23 months at
community-level: Results from a cluster randomized controlled trial in Malawi.
AB - BACKGROUND: Low dietary quality and quantity and inappropriate feeding practices
can cause undernutrition. Poor nutritional status in early childhood is
associated with growth faltering. The objective of the study was to assess the
potential of community-based nutrition education to improve height-for-age z
scores in children 6-23 months of age. METHODS AND FINDINGS: We carried out a
cluster-randomized-controlled trial to assess the effectiveness of nutrition
education. A total of 24 Extension Planning Area Sections served as clusters. The
selection criteria were: the position of the extension officer was staffed and
the sections had been selected by the project for activities in its first project
year. The sections were randomized into intervention and control restricted on
mean height for age Z-score using baseline information. In the intervention area,
food security activities and community-based nutrition education was implemented.
The control area received food security activities only. At baseline (2011) and
endline (2014), caregivers with a child below two years of age were enrolled.
Data assessment included anthropometric measurements, interviews on socio
economic status, dietary intake and feeding practices. A difference-in
differences estimator was used to calculate intervention effects. A positive
impact on child dietary diversity was observed (B (SE) = 0.39 (0.15), p = 0.01;
95%CI 0.09-0.68). There was a non-significant positive intervention effect on
mean height-for-age z-scores (B (SE) = 0.17 (0.12), p = 0.15; 95%CI -0.06-0.41).
LIMITATIONS: The 24h dietary recalls used to measure dietary diversity did not
consider quantities of consumed foods. Unrecorded poor quality of consumed foods
might have masked a potential benefit of increased child dietary diversity on
growth. CONCLUSIONS: Participatory community-based nutrition education for
caregivers improved child dietary diversity even in a food insecure area.
Nutrition education should be part of programs in food insecure settings aiming
at ameliorating food insecurity among communities.
PMID- 28426679
TI - Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using
attractive toxic sugar baits (ATSB).
AB - INTRODUCTION: Attractive Toxic Sugar Baits (ATSB) is a new vector control method
that meets Integrated Vector Management (IVM) goals. In an experimental design,
this study aimed to determine effects of ATSB on control of Phlebotomus papatasi,
as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province,
center of Iran. METHODS: In a cross-sectional design, boric acid was mixed with
brown sugar solution and tested as toxic baits for P. papatasi. Two methods were
utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs;
and (b) setting ATSB-treated barrier fences in front of colonies at 500 m
distance from the houses in outskirts of villages. In order to examine the
residual efficacy rate of ATSB-treated barrier fences, the bioassay test was
used. Density of P. papatasi sandflies was measured using sticky and light traps
biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used.
Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi
population. Besides that, ATSB spraying on plants led to more than 5 times
reduction in P. papatasi population. CONCLUSIONS: Comparing the incidence of
leishmaniasis in treated villages before and after the study showed that the
incidence was statistically reduced. Therefore, ATSB is an effective method to
control vectors and prevent leishmaniasis.
PMID- 28426680
TI - Echocardiographic findings in infants with presumed congenital Zika syndrome:
Retrospective case series study.
AB - OBJECTIVE: To report the echocardiographic evaluation of 103 infants with
presumed congenital Zika syndrome. METHODS: An observational retrospective study
was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP),
Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants
had microcephaly and head computed tomography findings compatible with congenital
Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of
23 infants. In 80 infants, the test was not performed because it was not
available at that time. All infants had negative serology for HIV, syphilis,
rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two
dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler
echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all
infants. RESULTS: 14/103 (13.5%) echocardiograms were compatible with congenital
heart disease: 5 with an ostium secundum atrial septal defect, 8 had a
hemodynamically insignificant small apical muscular ventricular septal defect and
one infant with dyspnea had a large membranous ventricular septal defect. The
echocardiograms considered normal included 45 infants with a persistent foramen
ovale and 16 with a minimum patent ductus arteriosus. CONCLUSIONS: Preliminarily
this study suggests that congenital Zika syndrome may be associated with an
increase prevalence of congenital heart disease. However the types of defects
noted were septal defects, a proportion of which would not be hemodynamically
significant.
PMID- 28426681
TI - Preventing, treating, and predicting barbering: A fundamental role for biomarkers
of oxidative stress in a mouse model of Trichotillomania.
AB - Barbering, where a "barber" mouse plucks hair from its cagemates or itself, is
both a spontaneously occurring abnormal behavior in mice and a well validated
model of Trichotillomania (TTM). N-Acetylcysteine, (NAC) a cysteine derived food
additive, is remarkably effective in treating TTM patients, but its mechanism of
action is unknown. Reactive Oxygen Species (ROS), also known as free radicals,
form as a natural byproduct of the normal metabolism of oxygen. Under normal
circumstances, cells are able to defend themselves against ROS damage with
antioxidant pathways. NAC is the precursor to the main antioxidant produced to
defend the brain. Therefore, we hypothesized that barbering is a disease of
oxidative stress, whereby ROS and/or a failure of antioxidant defenses leads to
neuronal damage that induces barbering in susceptible animals. We tested this
hypothesis in 32 female C57BL/6J mice by treating half with 1g/kg BW/day of NAC
in their diet, and testing for protection against developing barbering behavior
and curing of barbering behavior, and simultaneously testing for a panel of
biomarkers of oxidative stress. NAC reduced the chance that mice would be
barbers, and this effect did not differ between healthy (i.e. prevention) and
affected animals (i.e. cure). Barbering animals had elevated urinary antioxidant
capacity, indicative of oxidative stress, at all timepoints. Additionally, after
treatment the risk of barbering increased with decreasing hydroxy-2'
deoxyguanosine (8-OHdG) levels, and with increasing glutathione (GSH) and
oxidized glutathione (GSSG) levels, further indicating that barbering mice were
under oxidative stress regardless of treatment with NAC. We did not find
compelling evidence that urinary total antioxidant capacity, or urinary 8-OHdG,
could predict response to NAC treatment. We conclude that NAC is effective in
preventing and/or curing barbering at least in part by promoting GSH synthesis,
thereby preventing oxidative damage.
PMID- 28426682
TI - Automated measurement of cattle surface temperature and its correlation with
rectal temperature.
AB - The body temperature of cattle varies regularly with both the reproductive cycle
and disease status. Establishing an automatic method for monitoring body
temperature may facilitate better management of reproduction and disease control
in cattle. Here, we developed an Automatic Measurement System for Cattle's
Surface Temperature (AMSCST) to measure the temperature of metatarsus by
attaching a special shell designed to fit the anatomy of cattle's hind leg. Using
AMSCST, the surface temperature (ST) on the metatarsus of the hind leg was
successively measured during 24 hours a day with an interval of one hour in three
tested seasons. Based on ST and rectal temperature (RT) detected by AMSCST and
mercury thermometer, respectively, a linear mixed model was established,
regarding both the time point and seasonal factors as the fixed effects. Unary
linear correlation and Bland-Altman analysis results indicated that the
temperatures measured by AMSCST were closely correlated to those measured by
mercury thermometer (R2 = 0.998), suggesting that the AMSCST is an accurate and
reliable way to detect cattle's body temperature. Statistical analysis showed
that the differences of STs among the three seasons, or among the different time
points were significant (P<0.05), and the differences of RTs among the different
time points were similarly significant (P<0.05). The prediction accuracy of the
mixed model was verified by 10-fold cross validation. The average difference
between measured RT and predicted RT was about 0.10 +/- 0.10 degrees C with the
association coefficient of 0.644, indicating the feasibility of this model in
measuring cattle body temperature. Therefore, an automated technology for
accurately measuring cattle body temperature was accomplished by inventing an
optimal device and establishing the AMSCST system.
PMID- 28426683
TI - Genome-wide identification and characterization of miRNAome from tomato (Solanum
lycopersicum) roots and root-knot nematode (Meloidogyne incognita) during
susceptible interaction.
AB - Root-knot nematodes (RKNs, Meloidogyne spp.) are the most damaging plant
parasites causing severe losses to crop production. The present study reports
genome-wide identification and characterization of both tomato and RKN miRNAs
simultaneously from RKN-infected susceptible tomato roots using high-throughput
sequencing technique. RNAseq data from 11 small RNA libraries derived from 5
disease development stages identified 281 novel miRNAs of tomato in addition to
52 conserved and 4 variants of conserved miRNAs. Additionally, the same set of
RNAseq data identified 38 conserved and 290 novel RKN miRNAs. Both tomato and RKN
miRNAs showed differential expression at 5 stages of disease development based on
digital expression profiles. In tomato, further validation through qRT-PCR
confirmed that majority of miRNAs were significantly upregulated during
susceptible response whereas downregulated during resistance response. The
predicted targets of 8 conserved and 1 novel miRNAs were validated through 5'RLM
RACE. A negative correlation between expression profiles of a few conserved
miRNAs (miR156, miR159, miR164 and miR396) and their targets (SBP, GAMYB-like,
NAC and GRF1 transcription factor) was confirmed. A novel Sly_miRNA996 also
showed a negative correlation with its target MYB-like transcription factor.
These results indicate that the conserved and novel tomato miRNAs are involved in
regulating developmental changes in host root during RKN infection. In RKN, the
targets of conserved miRNAs were also predicted and a few of their predicted
target genes are known to be involved in nematode parasitism. Further, the
potential roles of both tomato and RKN miRNAs have been discussed.
PMID- 28426684
TI - Long-term results after transplantation of pediatric liver grafts from donation
after circulatory death donors.
AB - BACKGROUND: Liver grafts from donation after circulatory death (DCD) donors are
increasingly accepted as an extension of the organ pool for transplantation.
There is little data on the outcome of liver transplantation with DCD grafts from
a pediatric donor. The objective of this study was to assess the outcome of liver
transplantation with pediatric DCD grafts and to compare this with the outcome
after transplantation of livers from pediatric donation after brain death (DBD)
donors. METHOD: All transplantations performed with a liver from a pediatric
donor (<=16 years) in the Netherlands between 2002 and 2015 were included.
Patient survival, graft survival, and complication rates were compared between
DCD and DBD liver transplantation. RESULTS: In total, 74 liver transplantations
with pediatric grafts were performed; twenty (27%) DCD and 54 (73%) DBD. The
median donor warm ischemia time (DWIT) was 24 min (range 15-43 min). Patient
survival rate at 10 years was 78% for recipients of DCD grafts and 89% for DBD
grafts (p = 0.32). Graft survival rate at 10 years was 65% in recipients of DCD
versus 76% in DBD grafts (p = 0.20). If donor livers in this study would have
been rejected for transplantation when the DWIT >=30 min (n = 4), the 10-year
graft survival rate would have been 81% after DCD transplantation. The rate of
non-anastomotic biliary strictures was 5% in DCD and 4% in DBD grafts (p = 1.00).
Other complication rates were also similar between both groups. CONCLUSIONS:
Transplantation of livers from pediatric DCD donors results in good long-term
outcome especially when the DWIT is kept <=30 min. Patient and graft survival
rates are not significantly different between recipients of a pediatric DCD or
DBD liver. Moreover, the incidence of non-anastomotic biliary strictures after
transplantation of pediatric DCD livers is remarkably low.
PMID- 28426685
TI - Human African trypanosomiasis control: Achievements and challenges.
AB - Sleeping sickness, also known as human African trypanosomiasis (HAT), is a
neglected disease that impacts 70 million people living in 1.55 million km2 in
sub-Saharan Africa. Since the beginning of the 20th century, there have been
multiple HAT epidemics in sub-Saharan Africa, with the most recent epidemic in
the 1990s resulting in about half a million HAT cases reported between 1990 and
2015. Here we review the status of HAT disease at the current time and the
toolbox available for its control. We also highlight future opportunities under
development towards novel or improved interventions.
PMID- 28426687
TI - Does ethnicity matter in risk and protective factors for suicide attempts and
suicide lethality?
AB - This study explored ethnic differences in risk and protective factors for suicide
attempts, for the major ethnic groups in Singapore, and ethnic differences in
prediction of lethality. Three years of medical records related to suicide
attempters (N = 666) who were admitted to the emergency department of a large
teaching hospital in Singapore were subjected to analysis. Of the sample, 69.2%
were female, 30.8% male; 63.8% Chinese, 15.8% Indian, and 15.0% Malay. Indians
were over-represented in this sample, as compared with the ethnic distribution in
the general population. Ages ranged from 10 to 85 years old (M = 29.7, SD =
16.1). Ethnic differences were found in risk and protective factors, and
perceived lethality of suicide attempts. All available variables were subjected
to regression analyses for Chinese, Indian and Malay attempters to arrive at
parsimonious models for prediction of perceived lethality. The findings were
discussed in regards to implications in assessment of suicide risk and primary
prevention for the multiethnic society in Singapore.
PMID- 28426686
TI - Reactive oxygen species are required for driving efficient and sustained aerobic
glycolysis during CD4+ T cell activation.
AB - The immune system is necessary for protecting against various pathogens. However,
under certain circumstances, self-reactive immune cells can drive autoimmunity,
like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors
to the immunopathology in T1D, and in order to drive optimal T cell activation,
third signal reactive oxygen species (ROS) must be present. However, the role ROS
play in mediating this process remains to be further understood. Recently,
cellular metabolic programs have been shown to dictate the function and fate of
immune cells, including CD4+ T cells. During activation, CD4+ T cells must
transition metabolically from oxidative phosphorylation to aerobic glycolysis to
support proliferation and effector function. As ROS are capable of modulating
cellular metabolism in other models, we sought to understand if blocking ROS also
regulates CD4+ T cell activation and effector function by modulating T cell
metabolism. To do so, we utilized an ROS scavenging and potent antioxidant
manganese metalloporphyrin (MnP). Our results demonstrate that redox modulation
during activation regulates the mTOR/AMPK axis by maintaining AMPK activation,
resulting in diminished mTOR activation and reduced transition to aerobic
glycolysis in diabetogenic splenocytes. These results correlated with decreased
Myc and Glut1 upregulation, reduced glucose uptake, and diminished lactate
production. In an adoptive transfer model of T1D, animals treated with MnP
demonstrated delayed diabetes progression, concurrent with reduced CD4+ T cell
activation. Our results demonstrate that ROS are required for driving and
sustaining T cell activation-induced metabolic reprogramming, and further support
ROS as a target to minimize aberrant immune responses in autoimmunity.
PMID- 28426688
TI - Vancomycin-associated acute kidney injury: A cross-sectional study from a single
center in China.
AB - OBJECTIVE: The objective of this study was to investigate the current situation
of vancomycin (VAN)-associated acute kidney injury (VA-AKI) in China and identify
the risk factors for VA-AKI, as well as to comprehensively examine the risk
related to concurrent drug use. Further, we assessed the outcomes of patients who
developed VA-AKI and the risk factors for these outcomes. Finally, we aimed to
provide suggestions for improving the prevention and treatment of VA-AKI in
China. METHODS: We conducted a retrospective observational study of inpatients
who had been treated with VAN between January 2013 and December 2013 at Peking
University First Hospital. AKI was defined as an increase in SCr of >=0.3 mg/dl
(>=26.5 MUmol/l) within 48 hours or an increase to >=1.5 times the baseline
certainly or presumably within the past 7 days. VA-AKI was defined as the
development of AKI during VAN therapy or within 7 days following the termination
of VAN therapy. In addition, we compared patients with NO-AKI, who did not
develop AKI during their hospitalization, with those with VA-AKI. RESULTS: Of the
934 patients treated with VAN during their hospital stay, 740 were included in
this study. Among those excluded, 38.1% (74/194) were excluded because of a lack
of data on serum creatinine (SCr). Among the included patients, 120 had confirmed
VA-AKI, with an incidence of 16.2% (120/740). Multiple logistic regression
analysis revealed that an elevated baseline estimated glomerular filtration rate
(eGFR) (odds ratio [OR] = 1.009; p = 0.017) and concomitant vasopressor therapy
(OR = 2.942; p = 0.009), nitrate use (OR = 2.869; p = 0.007), imipenem-cilastatin
treatment (OR = 4.708; p = 0.000), and contrast medium administration (OR = 6.609
p = 0.005) were independent risk factors for VA-AKI; in addition, the receipt of
orthopedic/trauma/burn surgery (OR = 0.3575; p = 0.011) and concomitant compound
glycyrrhizin use (OR = 0.290; p = 0.017) were independent protective factors for
VA-AKI. Multiple logistic regression analysis also demonstrated that among the
patients who developed VA-AKI, coronary heart disease (CHD) (OR = 12.6; p =
0.006) and concomitant vasopressor therapy (OR = 15.4; p = 0.001) were
independent risk factors for death. We also evaluated the factors influencing
improvement of renal function. Multiple logistic regression analysis demonstrated
that CHD (OR = 8.858, p = 0.019) and concomitant contrast medium administration
(OR = 9.779, p = 0.005) were independent risk factors and that simultaneous beta
blocker treatment (OR = 0.124, p = 0.001) was an independent protective factor
for improvement of renal function. CONCLUSION: Patients treated with VAN received
insufficient monitoring of SCr and inadequate therapeutic drug monitoring. We
recommend that hospitals increase their investment in clinical pharmacists. An
elevated baseline eGFR and concomitant vasopressor therapy, nitrate use, imipenem
cilastatin treatment, and contrast medium administration were independent risk
factors for VA-AKI; in addition, orthopedic/trauma/burn surgery and concomitant
compound glycyrrhizin use were independent protective factors for VA-AKI.
PMID- 28426689
TI - Preference index supported by motivation tests in Nile tilapia.
AB - The identification of animal preferences is assumed to provide better rearing
environments for the animals in question. Preference tests focus on the frequency
of approaches or the time an animal spends in proximity to each item of the
investigated resource during a multiple-choice trial. Recently, a preference
index (PI) was proposed to differentiate animal preferences from momentary
responses (Sci Rep, 2016, 6:28328, DOI: 10.1038/srep28328). This index also
quantifies the degree of preference for each item. Each choice response is also
weighted, with the most recent responses weighted more heavily, but the index
includes the entire bank of tests, and thus represents a history-based approach.
In this study, we compared this PI to motivation tests, which consider how much
effort is expended to access a resource. We performed choice tests over 7
consecutive days for 34 Nile tilapia fish that presented with different colored
compartments in each test. We first detected the preferred and non-preferred
colors of each fish using the PI and then tested their motivation to reach these
compartments. We found that fish preferences varied individually, but the results
were consistent with the motivation profiles, as individual fish were more
motivated (the number of touches made on transparent, hinged doors that prevented
access to the resource) to access their preferred items. On average, most of the
34 fish avoided the color yellow and showed less motivation to reach yellow and
red colors. The fish also exhibited greater motivation to access blue and green
colors (the most preferred colors). These results corroborate the PI as a
reliable tool for the identification of animal preferences. We recommend this
index to animal keepers and researchers to identify an animal's preferred
conditions.
PMID- 28426690
TI - Phenotypic characterization and anticancer capacity of CD8+ cytokine-induced
killer cells after antigen-induced expansion.
AB - Cytokine-induced killer cells (CIK) have been used in clinic for adoptive
immunotherapy in a variety of malignant tumors and have improved the prognosis of
cancer patients. However, there are individual differences in the CIK cell
preparations including the obvious differences in the ratio of effector CIK cells
among different cancer patients. Infusion of such heterogeneous immune cell
preparation is an important factor that would affect the therapeutic efficacy. We
report here the enrichment and expansion of CD8+ cells from CIK cells cultured
for one week using magnetic activated cell sorting (MACS). These enriched CD8+
CIK cells expressed T cell marker CD3 and antigen recognition receptor NKG2D.
Phenotypic analysis showed that CD8+ CIK cells contained 32.4% of CD3+ CD56+
natural killer (NK)-like T cells, 23.6% of CD45RO+ CD28+, and 50.5% of CD45RA+
CD27+ memory T cells. In vitro cytotoxic activity assay demonstrated that the
enriched CD8+ CIK cells had significant cytotoxic activity against K562 cells and
five ovarian cancer cell lines. Intriguingly, CD8+ CIK cells had strong cytotoxic
activity against OVCAR3 cells that has weak binding capability to NKG2D. Flow
cytometry and quantitative RT-PCR analysis revealed that OVCAR3 cells expressed
HLA-I and OCT4 and Sox2, suggesting that CD8+ CIK cells recognize surface antigen
via specific T cell receptor and effectively kill the target cells. The results
suggest that transplantation of such in vitro enriched and expanded OCT4-specific
CD8+ CIK cells may improve the specific immune defense mechanism against cancer
stem cells, providing a novel avenue of cancer stem cell targeted immunotherapy
for clinical treatment of ovarian cancer.
PMID- 28426691
TI - Climatic factors driving vegetation declines in the 2005 and 2010 Amazon
droughts.
AB - Along with global climate change, the occurrence of extreme droughts in recent
years has had a serious impact on the Amazon region. Current studies on the
driving factors of the 2005 and 2010 Amazon droughts has focused on the influence
of precipitation, whereas the impacts of temperature and radiation have received
less attention. This study aims to explore the climate-driven factors of
Amazonian vegetation decline during the extreme droughts using vegetation index,
precipitation, temperature and radiation datasets. First, time-lag effects of
Amazonian vegetation responses to precipitation, radiation and temperature were
analyzed. Then, a multiple linear regression model was established to estimate
the contributions of climatic factors to vegetation greenness, from which the
dominant climate-driving factors were determined. Finally, the climate-driven
factors of Amazonian vegetation greenness decline during the 2005 and 2010
extreme droughts were explored. The results showed that (i) in the Amazon
vegetation greenness responded to precipitation, radiation and temperature, with
apparent time lags for most averaging interval periods associated with vegetation
index responses of 0-4, 0-9 and 0-6 months, respectively; (ii) on average, the
three climatic factors without time lags explained 27.28+/-21.73% (mean+/-1 SD)
of vegetation index variation in the Amazon basin, and this value increased by
12.22% and reached 39.50+/-27.85% when time lags were considered; (iii)
vegetation greenness in this region in non-drought years was primarily affected
by precipitation and shortwave radiation, and these two factors altogether
accounted for 93.47% of the total explanation; and (iv) in the common epicenter
of the two droughts, pixels with a significant variation in precipitation,
radiation and temperature accounted for 36.68%, 40.07% and 10.40%, respectively,
of all pixels showing a significant decrease in vegetation index in 2005, and
15.69%, 2.01% and 45.25% in 2010, respectively. Overall, vegetation greenness
declines during the 2005 and 2010 extreme droughts were adversely influenced by
precipitation, radiation and temperature; this study provides evidence of the
influence of multiple climatic factors on vegetation during the 2005 and 2010
Amazon droughts.
PMID- 28426692
TI - What is adaptation by natural selection? Perspectives of an experimental
microbiologist.
AB - Ever since Darwin, the role of natural selection in shaping the morphological,
physiological, and behavioral adaptations of animals and plants across
generations has been central to understanding life and its diversity. New
discoveries have shown with increasing precision how genetic, molecular, and
biochemical processes produce and express those organismal features during an
individual's lifetime. When it comes to microorganisms, however, understanding
the role of natural selection in producing adaptive solutions has historically
been, and sometimes continues to be, contentious. This tension is curious because
microbes enable one to observe the power of adaptation by natural selection with
exceptional rigor and clarity, as exemplified by the burgeoning field of
experimental microbial evolution. I trace the development of this field, describe
an experiment with Escherichia coli that has been running for almost 30 years,
and highlight other experiments in which natural selection has led to interesting
dynamics and adaptive changes in microbial populations.
PMID- 28426694
TI - Prediction of atherosclerotic cardiovascular disease mortality in a nationally
representative cohort using a set of risk factors from pooled cohort risk
equations.
AB - The American College of Cardiology/American Heart Association developed Pooled
Cohort equations to estimate atherosclerotic cardiovascular disease (ASCVD) risk.
It is unclear how well the equations predict ASCVD mortality in a nationally
representative cohort. We used the National Health and Nutrition Examination
Survey (NHANES) 1988-1994 and Linked Mortality through 2006 (n = 6,644). Among
participants aged 40-79 years without ASCVD at baseline, we used Cox proportional
hazard models to estimate the 10-year probability of ASCVD death by sex and race
ethnicity (non-Hispanic white (NHW), non-Hispanic black (NHB) and Mexican
American (MA)). We estimated the discrimination and calibration for each sex-race
ethnicity model. We documented 288 ASCVD deaths during 62,335 person years. The
Pooled Cohort equations demonstrated moderate to good discrimination for ASCVD
mortality, with modified C-statistics of 0.716 (95% CI 0.663-0.770), 0.794 (0.734
0.854), and 0.733 (0.654-0.811) for NHW, NHB and MA men, respectively. The
corresponding C-statistics for women were 0.781 (0.718-0.844), 0.702 (0.633
0.771), and 0.789 (CI 0.721-0.857). Modified Hosmer-Lemeshow chi2 suggested
adequate calibration for NHW, NHB and MA men, and MA women (p-values: 0.128,
0.295, 0.104 and 0.163 respectively). The calibration was inadequate for NHW and
NHB women (p<0.05). In this nationally representative cohort, the Pooled Cohort
equations performed adequately to predict 10-year ASCVD mortality for NHW and NHB
men, and MA population, but not for NHW and NHB women.
PMID- 28426693
TI - Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung
maturation in mice.
AB - BACKGROUND: Oxygen supply as a lifesaving intervention is frequently used to
treat preterm infants suffering additionally from possible prenatal or perinatal
pathogen features. The impact of oxygen and/or physical lung injury may influence
the morphological lung development, leading to a chronic postnatal lung disease
called bronchopulmonary dysplasia (BPD). At present different experimental BPD
models are used. However, there are no systematic comparative studies regarding
different influences of oxygen on morphological lung maturation. OBJECTIVE: We
investigated the influence of prenatal hypoxia and/or postnatal hyperoxia on
morphological lung maturation based on stereological parameters, to find out
which model best reflects morphological changes in lung development comparable
with alterations found in BPD. METHODS: Pregnant mice were exposed to normoxia,
the offspring to normoxia (No/No) or to hyperoxia (No/Hyper). Furthermore,
pregnant mice were exposed to hypoxia and the offspring to normoxia (Hypo/No) or
to hyperoxia (Hypo/Hyper). Stereological investigations were performed on all
pups at 14 days after birth. RESULTS: Compared to controls (No/No) 1) the lung
volume was significantly reduced in the No/Hyper and Hypo/Hyper groups, 2) the
volume weighted mean volume of the parenchymal airspaces was significantly higher
in the Hypo/Hyper group, 3) the total air space volume was significantly lower in
the No/Hyper and Hypo/Hyper groups, 4) the total septal surface showed
significantly lower values in the No/Hyper and Hypo/Hyper groups, 5) the wall
thickness of septa showed the highest values in the Hypo/Hyper group without
reaching significance, 6) the volume density and the volume weighted mean volume
of lamellar bodies in alveolar epithelial cells type II (AEII) were significantly
lower in the Hypo/Hyper group. CONCLUSION: Prenatal hypoxia and postnatal
hyperoxia differentially influence the maturation of lung parenchyma. In 14 day
old mice a significant retardation of morphological lung development leading to
BPD-like alterations indicated by different parameters was only seen after
hypoxia and hyperoxia.
PMID- 28426695
TI - A comparative study of pediatric open pyeloplasty, laparoscopy-assisted
extracorporeal pyeloplasty, and robot-assisted laparoscopic pyeloplasty.
AB - PURPOSE: To compare the outcomes of open pyeloplasty (OP), laparoscopy-assisted
extracorporeal (LEXP), and robotic-assisted laparoscopic pyeloplasty (RALP) for
ureteropelvic junction obstruction in pediatric patients. METHODS: We
retrospectively reviewed the age-matched cohort of 30 children who underwent OP,
30 who underwent LEXP, and 10 who underwent RALP at a single institution, from
1996 to 2014. Pre- and post-operative variables including success rate were
compared among surgical groups. RESULTS: The mean age of the patients was 120.2
months, the Society for Fetal Urology grade was 3.6, the anteroposterior diameter
was 3.1 cm, and the renal relative function was 44.0%. The distribution of
laterality, mean body mass index, and preoperative anteroposterior pelvic
diameter on ultrasound did not differ among groups. The mean length of hospital
stay was significantly shorter in the RALP group (3.2 days) than in the OP (6.6
days) and LEXP (5.8 days) groups (p<0.001). The duration of analgesics use was
shorter in the RALP group (1.1 days) than in the other groups (p<0.001). During
the mean follow-up period of 49.0, 20.1, and 16.6 months, the success rate was
96.7%, 89.7%, and 100% in the OP, LEXP, and RALP groups, respectively, although
this difference was not statistically different (p = 0.499). In multivariate
regression analysis, the presence of crossing vessels was the only factor that
decreased the success rate (hazard ratio: 46.09, 95% confidence interval: 2.41
879.6, p = 0.011). CONCLUSIONS: Patients who undergo RALP have a reduced hospital
stay and lower use of pain medication; however, there is no difference in the
success rates for OP, LP, and RALP surgeries. The presence of crossing vessels is
a negative prognostic indicator for surgical outcome regardless of the surgical
method.
PMID- 28426696
TI - Heritability of brain volume on MRI in middle to advanced age: A twin study of
Japanese adults.
AB - Brain atrophy is part of the aging process and accelerated by neurodegenerative
diseases, so an understanding of the background heritability of brain volume is
essential. The purpose of this study was to determine the heritability of brain
volume in middle to advanced age East Asian adults, an age group less studied and
an ethnicity not previously studied. 3T magnetic resonance images were obtained
and volumetric analyses conducted for a total of 74 individuals, 20 monozygotic
twin pairs (mean age 61y min 41y max 75y) and 17 dizygotic twin pairs (mean age
64y min 41y max 85y). Total brain volume and a further seven regions were
assessed, including lobar volumes, lateral divisions, and separated grey and
white matter. Additive genetics and unique environment (AE) models for global
brain volumes including total brain (90%), grey matter (91%) and white matter
(84%) and many lobar volumes demonstrated high heritability in our study
population. Our results present the heritability of brain volume in middle to
advanced age as possibly higher in East Asian adults.
PMID- 28426697
TI - Perceived conflict of interest in health science partnerships.
AB - University scientists conducting research on topics of potential health concern
often want to partner with a range of actors, including government entities, non
governmental organizations, and private enterprises. Such partnerships can
provide access to needed resources, including funding. However, those who observe
the results of such partnerships may judge those results based on who is
involved. This set of studies seeks to assess how people perceive two
hypothetical health science research collaborations. In doing so, it also tests
the utility of using procedural justice concepts to assess perceptions of
research legitimacy as a theoretical way to investigate conflict of interest
perceptions. Findings show that including an industry collaborator has clear
negative repercussions for how people see a research partnership and that these
perceptions shape people's willingness to see the research as a legitimate source
of knowledge. Additional research aimed at further communicating procedures that
might mitigate the impact of industry collaboration is suggested.
PMID- 28426698
TI - Extensive alterations of blood metabolites in pediatric cerebral malaria.
AB - Cerebral malaria (CM) presents as an encephalopathy and is due to infection with
Plasmodium falciparum. Patients are comatose, often with fever, recurrent
seizures and this condition is associated with a high mortality rate. The
etiology of the coma and seizures are poorly understood. Circulating small
molecules and lipids have bioactive functions and alterations in their
concentrations have been implicated in seizure disorders and other forms of
encephalopathy. We carried out a comprehensive analysis of blood metabolites
during CM to explore a biochemical basis of this encephalopathy. A paired
metabolomics analysis was performed on the plasma samples of Malawian children (n
= 11) during CM and at convalescence thirty days later, to identify
differentially abundant molecules associated with CM. We also report plasma
molecules associated with CM mortality (n = 4) compared to survival (n = 19).
Plasma metabolites were identified through ultra high performance liquid
chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry
to maximize compound detection and accuracy and then compared to a library for
identification. We detected a total of 432 small molecules in the plasma and 247
metabolites were significantly differentially abundant between CM and
convalescence (p < 0.05, FDR < 0.10). These represented global changes across
many classes of molecules including lipids, amino acids and hemoglobin
metabolites. We observed significant changes in molecules that could impact
neurologic function during CM; these include increased levels of kynurenate and
decreased indolepropionate, glutamate, arginine and glutamine. Moreover, 1
methylimidazoleacetate, kyurenate, arachidonic acid and dimethylarginine were
associated with mortality (p < 0.05, fold change > 1.2). These results highlight
the broad changes in blood chemistry during CM. We have identified metabolites
that may impact central nervous system physiology and disease outcomes and can be
further explored for their mechanistic roles into the pathophysiology of CM.
PMID- 28426699
TI - Anti-IL-20 monoclonal antibody inhibited inflammation and protected against
cartilage destruction in murine models of osteoarthritis.
AB - Osteoarthritis (OA) is a degenerative joint disease characterized by progressive
destruction of articular cartilage. Interleukin (IL)-20 is a proinflammatory
cytokine involved in the pathogenesis of rheumatoid arthritis. We investigated
the role of IL-20 in OA and evaluated whether anti-IL-20 antibody (7E) treatment
attenuates disease severity in murine models of surgery-induced OA.
Immunohistochemical staining was used to detect IL-20 and its receptors
expression in synovial tissue and cartilage from OA patients, and in OA synovial
fibroblasts (OASFs) and chondrocytes (OACCs) from rodents with surgery-induced
OA. RTQ-PCR and western blotting were used to determine IL-20-regulated OA
associated gene expression in OASFs and OACCs. OA rats and OA mice were treated
with 7E. Arthritis severity was determined based on the degree of cartilage
damage and the arthritis severity score. We found that IL-20 and its receptors
were expressed in OASFs and OACCs. IL-20 induced TNF-alpha, IL-1beta, MMP-1, and
MMP-13 expression by activating ERK-1/2 and JNK signals in OASFs. IL-20 not only
upregulated MCP-1, IL-6, MMP-1, and MMP-13 expression, but also downregulated
aggrecan, type 2 collagen, TGF-beta, and BMP-2 expression in OACCs. Arthritis
severity was significantly lower in 7E-treated OA rats, and 7E- or MSC-treated OA
mice. Therefore, we concluded that IL-20 was involved in the progression and
development of OA through inducing proinflammatory cytokines and OA-associated
gene expression in OASFs and OACCs. 7E reduced the severity of arthritis in
murine models of surgery-induced OA. Our findings provide evidence that IL-20 is
a novel target and that 7E is a potential therapeutic agent for OA.
PMID- 28426700
TI - Southern Tunisia: A still high endemicity area for hepatitis A.
AB - BACKGROUND: Hepatitis A (HAV) and E (HEV) viruses are responsible for enterically
transmitted hepatitis. Tunisia is reported to be of intermediate endemicity for
HAV and of low seroprevalence for HEV; however, data from rural areas of South
Tunisia are lacking. METHODS: Sera from 216 asymptomatic pregnant women and from
92 patients with acute hepatitis were collected between October 2014 and November
2015. Total and IgM anti-HAV immunoglobulins and anti-HEV IgG and IgM were
investigated. Anti-HAV IgM-positive samples were subjected to RT-PCR targeting
the VP1/2A region and sequenced. HEV IgM positive samples and all samples from
acute hepatitis patients were assessed for HEV RNA. RESULTS: Among pregnant women
(mean age 32+/-8), HAV seroprevalence was 98.6%, none presented anti-HAV IgM; HEV
seroprevalence was 5.1% and three presented weakly reactive anti-HEV IgM without
detectable RNA. Among acute hepatitis patients (mean age 18.5 +/- 14), HEV
seroprevalence was 19,5%, none presented anti-HEV IgM, nor HEV RNA. HAV
seroprevalence exceeded 90% by age 5 and acute HAV infection was detected in 20
patients (21,7%), younger than patients with other hepatitis causes (9,8 years
vs. 20,4 years, p = 0,004); 65% were male. Most acute HAV infections were
observed in a coastal area where HAV infections represented 52% of hepatitis
etiology. Phylogenetic analysis identified genotype IA strains, clustering close
to previously published Tunisian sequences. CONCLUSION: The present study
confirmed a low HEV endemicity and evidenced a still high level of HAV
circulation in Southern Tunisia, suggesting distinct dissemination patterns for
these viruses.
PMID- 28426701
TI - Exploratory study on the effect of osteoactivin on muscle regeneration in a rat
volumetric muscle loss model.
AB - Wounds causing extensive injury loss of muscle, also known as volumetric muscle
loss (VML), are frequently associated with high-energy civilian trauma and combat
related extremity injuries. Currently, no effective clinical therapy is available
for promoting de novo muscle tissue regeneration to restore muscle function
following VML. Recent studies have shown evidence that osteoactivin (OA), a
transmembrane glycoprotein, has the ability to prevent skeletal muscle atrophy in
response to denervation. Therefore the objective of this study is to investigate
the potential regenerative effect of OA embedded and delivered via a cross-linked
gelatin hydrogel within a volumetric tibialis anterior muscle defect in a rat
model. After 4 weeks, however, no evidence for muscle formation was found in
defects treated with either low (5 MUg/ml) or high (50 MUg/ml) OA. It is possible
that a different delivery scaffold, delivery kinetics, or OA concentration may
have yielded an alternate outcome, or it is also possible that the
spaciostructural environment of VML, or the local (versus systemic) delivery of
OA, simply does not support any potential regenerative activity of OA in VML.
Together with prior work, this study demonstrates that an efficacious and
scalable therapy for regenerating muscle volume and function in VML remains a
veritable clinical challenge worthy of continued future research efforts.
PMID- 28426702
TI - Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease
activity: A prospective, non-randomized pilot study.
AB - Natalizumab is an effective therapy for multiple sclerosis (MS). Its
effectiveness has been demonstrated in several clinical and imaging studies. The
objective of this study was to further demonstrate the efficacy of natalizumab
using a comprehensive battery of clinical and imaging markers in the same cohort
of patients followed longitudinally, hence capturing the multi-faceted nature of
the MS disease process. A prospective, open-label, pilot study of 20 MS patients
treated with natalizumab was conducted. High resolution MRI, Symbol-Digit
Modalities Test (SDMT), and Optical Coherence Tomography (OCT) scans were
obtained at baseline, 48, and 96 weeks. 15 patients completed the study.
Natalizumab treatment decreased Expanded Disability Status Scale score (EDSS) and
no change in SDMT, Brain Parenchymal Fraction (BPF), or any of the OCT markers of
retinal degeneration was observed. Thalamic and whole brain volume as assessed by
Percentage Brain Volume Change (PBVC) showed continuous deterioration. Higher
baseline T2 lesion load correlated with increased rate of PBVC at 96-weeks (r =
0.566, R2 = 0.320, p = 0.035) and thalamic volume loss (r = -0.586, R2 = 0.344, p
= 0.027). Most patients, 93%, achieved no evidence of disease activity (NEDA) at
2 years, likely due to early disease duration and lower initial baseline lesion
load. This study further demonstrates stabilization of clinical and imaging
markers of disease activity during natalizumab treatment.
PMID- 28426703
TI - Effects of over-expressing a native gene encoding 5-enolpyruvylshikimate-3
phosphate synthase (EPSPS) on glyphosate resistance in Arabidopsis thaliana.
AB - Widespread overuse of the herbicide glyphosate, the active ingredient in
RoundUp(r), has led to the evolution of glyphosate-resistant weed biotypes, some
of which persist by overproducing the herbicide's target enzyme, 5
enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS is a key enzyme in the
shikimic acid pathway for biosynthesis of aromatic amino acids, lignin, and
defensive compounds, but little is known about how overproducing EPSPS affects
downstream metabolites, growth, or lifetime fitness in the absence of glyphosate.
We are using Arabidopsis as a model system for investigating phenotypic effects
of overproducing EPSPS, thereby avoiding confounding effects of genetic
background or other mechanisms of herbicide resistance in agricultural weeds.
Here, we report results from the first stage of this project. We designed a
binary vector expressing a native EPSPS gene from Arabidopsis under control of
the CaMV35S promoter (labelled OX, for over-expression). For both OX and the
empty vector (labelled EV), we obtained nine independent T3 lines. Subsets of
these lines were used to characterize glyphosate resistance in greenhouse
experiments. Seven of the nine OX lines exhibited enhanced glyphosate resistance
when compared to EV and wild-type control lines, and one of these was discarded
due to severe deformities. The remaining six OX lines exhibited enhanced EPSPS
gene expression and glyphosate resistance compared to controls. Glyphosate
resistance was correlated with the degree of EPSPS over-expression for both
vegetative and flowering plants, indicating that glyphosate resistance can be
used as a surrogate for EPSPS expression levels in this system. These findings
set the stage for examination of the effects of EPSPS over-expression on fitness
related traits in the absence of glyphosate. We invite other investigators to
contact us if they wish to study gene expression, downstream metabolic effects,
and other questions with these particular lines.
PMID- 28426704
TI - Population effect model identifies gene expression predictors of survival
outcomes in lung adenocarcinoma for both Caucasian and Asian patients.
AB - BACKGROUND: We analyzed and integrated transcriptome data from two large studies
of lung adenocarcinomas on distinct populations. Our goal was to investigate the
variable gene expression alterations between paired tumor-normal tissues and
prospectively identify those alterations that can reliably predict lung disease
related outcomes across populations. METHODS: We developed a mixed model that
combined the paired tumor-normal RNA-seq from two populations. Alterations in
gene expression common to both populations were detected and validated in two
independent DNA microarray datasets. A 10-gene prognosis signature was developed
through a l1 penalized regression approach and its prognostic value was evaluated
in a third independent microarray cohort. RESULTS: Deregulation of apoptosis
pathways and increased expression of cell cycle pathways were identified in
tumors of both Caucasian and Asian lung adenocarcinoma patients. We demonstrate
that a 10-gene biomarker panel can predict prognosis of lung adenocarcinoma in
both Caucasians and Asians. Compared to low risk groups, high risk groups showed
significantly shorter overall survival time (Caucasian patients data: HR = 3.63,
p-value = 0.007; Asian patients data: HR = 3.25, p-value = 0.001). CONCLUSIONS:
This study uses a statistical framework to detect DEGs between paired tumor and
normal tissues that considers variances among patients and ethnicities, which
will aid in understanding the common genes and signalling pathways with the
largest effect sizes in ethnically diverse cohorts. We propose multifunctional
markers for distinguishing tumor from normal tissue and prognosis for both
populations studied.
PMID- 28426706
TI - Bearing-based localization for leader-follower formation control.
AB - The observability of the leader robot system and the leader-follower formation
control are studied. First, the nonlinear observability is studied for when the
leader robot observes landmarks. Second, the system is shown to be completely
observable when the leader robot observes two different landmarks. When the
leader robot system is observable, multi-robots can rapidly form and maintain a
formation based on the bearing-only information that the follower robots observe
from the leader robot. Finally, simulations confirm the effectiveness of the
proposed formation control.
PMID- 28426705
TI - An automated algorithm for the detection of cortical interruptions on high
resolution peripheral quantitative computed tomography images of finger joints.
AB - OBJECTIVES: To introduce a fully-automated algorithm for the detection of small
cortical interruptions (>=0.246mm in diameter) on high resolution peripheral
quantitative computed tomography (HR-pQCT) images, and to investigate the
additional value of manual correction of the automatically obtained contours
(semi-automated procedure). METHODS: Ten metacarpophalangeal joints from seven
patients with rheumatoid arthritis (RA) and three healthy controls were imaged
with HR-pQCT. The images were evaluated by an algorithm according to the fully-
and semi-automated procedure for the number and surface of interruptions per
joint. Reliability between the fully- and semi-automated procedure and between
two independent operators was tested using intra-class correlation coefficient
(ICC) and the proportion of matching interruptions. Validity of single
interruptions detected was tested by comparing it to visual scoring, as gold
standard. The positive predictive value (PPV) and sensitivity were calculated.
RESULTS: The median number of interruptions per joint was 14 (range 2 to 59) and
did not significantly differ between the fully- and semi-automated procedure (p =
0.37). The median interruption surface per joint was significantly higher with
the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and
6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi
automated procedure for both the number and surface of interruptions (ICC>=0.95)
and the proportion of matching interruptions was high (>=76%). Also the inter
operator reliability was almost perfect (ICC>=0.97, proportion of matching
interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from
69.7% to 76.3%. Most interruptions detected with the algorithm, did show an
interruption on a 2D grayscale image. However, this interruption did not meet the
criteria of an interruption with visual scoring. CONCLUSION: The algorithm for HR
pQCT images detects cortical interruptions, and its interruption surface.
Reliability and validity was comparable for the fully- and semi-automated
procedures. However, we advise the use of the semi-automated procedure to assure
quality. The algorithm is a promising tool for a sensitive and objective
assessment of cortical interruptions in finger joints assessed by HR-pQCT.
PMID- 28426707
TI - Rare cell isolation and recovery on open-channel microfluidic chip.
AB - The ability to accurately detect and analyze rare cells in a cell population is
critical not only for the study of disease progression but also for next flow
cytometry systems in clinical application. Here, we report the development of a
prototype device, the 'Rare cell sorter', for isolating and recovering single
rare cells from whole blood samples. On this device, we utilized an open-channel
microfluidic chip for rare cell isolation. And the advantage of open-channel
allows us to recover the isolated rare cell directly from the chip. We set the
circulating tumor cell (CTC) as a target cell. For the clinical experiment, CTCs
were isolated from blood samples collected from patients with metastatic breast
cancer and healthy volunteers. There was a significant difference in the number
of CTCs between the patients with metastatic breast cancer and healthy
volunteers. To evaluate the damage to cells during isolation and recovery, we
performed an RNA integrity assay using RNA extracted from CTCs recovered from the
chip and found that our process for single CTC isolation and recovery is mild
enough for gene analysis of CTCs.
PMID- 28426708
TI - Let's decide together: Differences between individual and joint delay
discounting.
AB - This study addressed the question whether or not social collaboration has an
effect on delay discounting, the tendency to prefer sooner but smaller over later
but larger delivered rewards. We applied a novel paradigm in which participants
executed choices between two gains in an individual and in a dyadic decision
making condition. We observed how participants reached mutual consent via
joystick movement coordination and found lower discounting and a higher
decisions' efficiency. In order to establish the underlying mechanism for dyadic
variation, we further tested whether these differences emerge from social
facilitation or inner group interchange.
PMID- 28426709
TI - Pdgfrb is a direct regulatory target of TGFbeta signaling in atrioventricular
cushion mesenchymal cells.
AB - Cushion formation is the initial step for the development of valvuloseptal
structures in mammalian hearts. TGFbeta signaling plays critical roles in
multiple steps of cushion morphogenesis. We used a newly developed conditional
immortal atrioventricular cushion mesenchymal cell line, tsA58-AVM, to identify
the TGFbeta regulatory target genes through microarray analysis. Expression of
~1350 genes was significantly altered by TGFbeta1 treatment. Subsequent
bioinformatic analysis of TGFbeta activated genes revealed that PDGF-BB signaling
is the top hit as the potential upstream regulator. Among the 37 target
molecules, 10 genes known to be involved in valve development and hemostasis were
selected for quantitative reverse transcription polymerase chain reaction (qRT
PCR) analysis. Our results confirmed that they are all upregulated by TGFbeta1
stimulation in tsA58-AVM cells and in primary atrioventricular cushion cells. We
focused on examining regulation of Pdgfrb by TGFbeta1, which encodes a tyrosine
kinase receptor for PDGF-BB. We found that the ~150bp Pdgfrb promoter can respond
to TGFbeta stimulation and that this response relies on the two SP1 binding sites
within the promoter. Co-immunoprecipitation analysis confirmed SP1 interacts with
SMAD2 in a TGFbeta-dependent fashion. Furthermore, SMAD2 is associated with the
Pdgfrb promoter and this association is diminished by knocking down expression of
Sp1. Our data therefore collectively suggest that upon TGFbeta stimulation, SP1
recruits SMAD2 to the promoter of Pdgfrb to up-regulate its expression and thus
Pdgfrb is a direct downstream target of the TGFbeta/SMAD2 signaling.
PMID- 28426710
TI - Change in iron metabolism in rats after renal ischemia/reperfusion injury.
AB - Previous studies have indicated that hepcidin, which can regulate iron efflux by
binding to ferroportin-1 (FPN1) and inducing its internalization and degradation,
acts as the critical factor in the regulation of iron metabolism. However, it is
unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury
(IRI). In this study, an IRI rat model was established via right renal excision
and blood interruption for 45 min in the left kidney, and iron metabolism indexes
were examined to investigate the change in iron metabolism and to analyze the
role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum
creatinine and blood urea nitrogen were found to be time-dependently increased
with different degrees of kidney injury. Regular variations in iron metabolism
indexes in the blood and kidneys were observed in renal IRI. Renal iron content,
serum iron and serum ferritin increased early after reperfusion and then
declined. Hepcidin expression in the liver significantly increased early after
reperfusion, and its serum concentration increased beginning at 8 h after
reperfusion. The splenic iron content decreased significantly in the early stage
after reperfusion and then increased time-dependently with increasing reperfusion
time, and the hepatic iron content showed a decrease in the early stage after
reperfusion. The early decrease of the splenic iron content and hepatic iron
content might indicate their contribution to the increase in serum iron in renal
IRI. In addition, the duodenal iron content showed time-dependently decreased
since 12 h after reperfusion in the IRI groups compared to the control group.
Along with the spleen, the duodenum might contribute to the decrease in serum
iron in the later stage after reperfusion. The changes in iron metabolism indexes
observed in our study demonstrate an iron metabolism disorder in renal IRI, and
hepcidin might be involved in maintaining iron homeostasis in renal IRI. These
findings might suggest a self-protection mechanism regulating iron homeostasis in
IRI and provide a new perspective on iron metabolism in attenuating renal IRI.
PMID- 28426711
TI - Proinsulin is stable at room temperature for 24 hours in EDTA: A clinical
laboratory analysis (adAPT 3).
AB - AIMS: Reference laboratories advise immediate separation and freezing of samples
for the assay of proinsulin, which limit its practicability for smaller centres.
Following the demonstration that insulin and C-peptide are stable in EDTA at room
temperature for at least 24hours, we undertook simple stability studies to
establish whether the same might apply to proinsulin. METHODS: Venous blood
samples were drawn from six adult women, some fasting, some not, aliquoted and
assayed immediately and after storage at either 4 degrees C or ambient
temperature for periods from 2h to 24h. RESULTS: There was no significant
variation or difference with storage time or storage condition in either
individual or group analysis. CONCLUSION: Proinsulin appears to be stable at room
temperature in EDTA for at least 24h. Immediate separation and storage on ice of
samples for proinsulin assay is not necessary, which will simplify sample
transport, particularly for multicentre trials.
PMID- 28426712
TI - The culturable mycobiota of Flabellia petiolata: First survey of marine fungi
associated to a Mediterranean green alga.
AB - Algae-inhabiting marine fungi represent a taxonomically and ecologically
interesting group of microorganisms still largely neglected, especially in
temperate regions. The aim of this study was to isolate and to identify the
culturable mycobiota associated with Flabellia petiolata, a green alga frequently
retrieved in the Mediterranean basin. Twenty algal thalli were collected from two
different sampling sites in the Mediterranean Sea (Elba Island, Italy). A
polyphasic approach showed the presence of a relevant alga-associated mycobiota
with 64 taxa identified. The fungal isolates belonged mainly to Ascomycota (61
taxa), while only three Basidiomycota were detected. The phylogenetic position of
sterile mycelia and cryptic taxa, inferred on the basis of LSU partial region,
highlighted the presence of putative new phylogenetic lineages within
Dothideomycetes and Sordariomycetes. This work represents the first quali
quantitative analysis of the culturable mycobiota associated to a green alga in
the Mediterranean Sea.
PMID- 28426713
TI - Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the
insulin signaling pathway.
AB - Knockout of metallothionein (MT) genes contributes to a heavier body weight in
early life and the potential to become obese through the intake of a high fat
diet (HFD) in mice. It has thus been suggested that MT genes regulate the
formation of adipose tissue, which would become the base for later HFD-induced
obesity. We evaluated the fat pads of mice during the lactation stage. The fat
mass and adipocyte size of MT1 and MT2 knockout mice were greater than those of
wild type mice. Next, we assayed the ability of small interfering RNA (siRNA) to
silence MT genes in the 3T3-L1 cell line. The expressions of MT1 and MT2 genes
were transiently upregulated during adipocyte differentiation, and the siRNA
pretreatment led to the suppression of the expression of both MT mRNAs and
proteins. The MT siRNA promoted lipid accumulation in adipocytes and caused
proliferation of post-confluent preadipocytes; these effects were suppressed by
an inhibitor of phosphatidylinositol 3-kinase (LY294002). In addition, MT siRNA
promoted insulin-stimulated phosphorylation of Akt, a downstream kinase of the
insulin signaling pathway. Enhanced lipid accumulation in 3T3-L1 cells resulting
from MT-gene silencing was inhibited by pretreatment with an antioxidant, N
acetylcysteine, used as a substitute for antioxidant protein MTs. These results
suggest that interference in MT expression enhanced the activation of the insulin
signaling pathway, resulting in higher lipid accumulation in 3T3-L1 adipocytes.
PMID- 28426714
TI - A genetic risk score for CAD, psychological stress, and their interaction as
predictors of CAD, fatal MI, non-fatal MI and cardiovascular death.
AB - BACKGROUND: Psychological stress is an independent risk factor for cardiovascular
disease (CVD), but the mechanism by which stress is associated with CVD is not
entirely understood. Although genetic factors are implied in both stress
responsivity and cardiovascular reactivity, no studies to date have investigated
their interactions with stress for cardiovascular end points. The objective was
to elucidate the association and interactions between a genetic risk score (GRS),
individual genetic variants and stress for three cardiovascular end points:
coronary artery disease (CAD), fatal myocardial infarction (MI), non-fatal MI,
and cardiovascular death. METHODS AND FINDINGS: 18,559 participants from the
Malmo Diet Cancer Study, a population-based prospective study, were included in
the analyses. Cox proportional hazards regression models were used and adjusted
for a large number of known predictors of cardiovascular end points. Mean follow
up time in years was 14.6 (CAD; n = 1938), 14.8 (fatal MI; n = 436), 14.8 (non
fatal MI; n = 1108), and 15.1 (cardiovascular death; n = 1071) respectively. GRS
was significantly associated with increased risks of CAD (top quartile hazard
ratio [HR], 1.72; 95% confidence interval [CI], 1.51-1.96), fatal MI (top
quartile HR, 1.62; 95%CI, 1.23-2.15), non-fatal MI (top quartile HR, 1.55; 95%CI,
1.31-1.84), and cardiovascular death (top quartile HR, 1.29; 95%CI, 1.08-1.53).
Stress was not independently associated with any end point and did not interact
with GRS. Four individual genetic variants interacted unfavorably with stress for
end points with mortality outcomes. CONCLUSION: A GRS composed of 50 SNPs and
predictive of CAD was found for the first time to also strongly predict fatal MI,
non-fatal MI and cardiovascular death. A stress-sensitive component of the GRS
was isolated on the basis of individual genetic variants that interacted
unfavorably with stress.
PMID- 28426715
TI - Acute hypoxia influences collagen and matrix metalloproteinase expression by
human keratoconus cells in vitro.
AB - Keratoconus (KC) is a progressive corneal ectasia linked to thinning of the
central cornea. Hard contact lenses, rigid gas permeable lenses, and scleral
lenses are the primary treatment modalities for early to mid- stages of KC to
correct refractive error and astigmatism that develops as a result of an
irregular corneal structure. These treatments are associated with significant
drawbacks, including reduced availability of the tear film and oxygen to the
corneal epithelium and stroma. However, it remains unknown whether hypoxia
affects corneal integrity in the KC pathobiology. A number of studies have
associated elevated oxidative stress with KC both in vitro and ex vivo. We
hypothesized that KC-derived corneal fibroblasts are more susceptible to hypoxia
induced oxidative stress compared to healthy controls leading to exacerbation of
corneal thinning in KC. This study investigated the effects of hypoxia on ECM
secretion, assembly, and matrix metalloproteinase (MMP) expression in human
corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs) in vitro.
HCFs and HKCs were cultured in 3D constructs for 3 weeks and maintained or
transferred to normoxic (21% O2) or hypoxic (2% O2) conditions, respectively, for
1 additional week. At the 4 week time-point, constructs were isolated and probed
for Collagen I, III, and V, keratocan and MMP-1, -2, -3, -9, and -13, as well as
hypoxia markers, hypoxia inducible factor-1alpha and lactoferrin. Conditioned
media was also collected and probed for Collagen I, III, and V by Western blot.
Thickness of the ECM assembled by HCFs and HKCs was measured using
immunofluorescence microscopy. Results showed that hypoxia significantly reduced
Collagen I secretion in HKCs, as well as upregulated the expression of MMP-1 and
2 with no significant effects on MMP-3, -9, or -13. ECM thickness was reduced in
both cell types following 1 week in a low oxygen environment. Our study shows
that hypoxia influences collagen and MMP expression by HKCs, which may have
consequential effects on ECM structure in the context of KC.
PMID- 28426716
TI - The yin and yang of leishmaniasis control.
PMID- 28426717
TI - Adjusting cryodiluent composition for improved post-thaw quality of rabbit
spermatozoa.
AB - Improved fertility following artificial insemination with frozen-thawed
spermatozoa would offer rabbit producers faster genetic improvement. Previous
work investigating cryoprotectants for rabbit spermatozoa have reported
inconsistent results. Semen was collected from three rabbit bucks by artificial
vagina and frozen using a standard procedure with varied cryodiluent components.
Post-thaw analysis encompassed motility, sperm kinematic parameters and acrosome
and membrane integrity. Spermatozoa were evaluated at 0, 2 and 4 h after thawing.
Experiment 1 compared diluents with 3.5% dimethyl sulfoxide (DMSO), 1.5%
acetamide, 1.75% DMSO + 0.75% acetamide or 3.5% DMSO + 1.5% acetamide. The
treatment that resulted in the highest post-thaw motility (P<0.001) and acrosome
integrity (P<0.001) was DMSO alone. Experiment 2 compared 3.5, 7 and 10% DMSO in
the cryodiluent. The best post-thaw sperm motility (P<0.001) and linearity (P =
.002) was in 3.5% DMSO, while 10% DMSO afforded higher acrosome/membrane
integrity at this last time point (P<0.05). Experiment 3 varied the cryodiluent
to contain either 9 or 17% egg yolk or 9 or 17% low density lipoproteins
extracted from whole egg yolk. The treatment with the best post-thaw result was
17% egg yolk (motility, P = 0.01; acrosome/membrane integrity, P<0.001).
Experiment 4 compared different carbohydrates in the cryodiluent; 50 mM glucose
(TCG), 25 mM glucose with 25 mM sucrose (TCGS low), or 50 mM glucose with 50 mM
sucrose (TCGS high). When data were pooled across time points, TCG had
significantly higher motility than TCGS high (P = 0.021), but was not different
from TCGS low. However, TCG had fewer spermatozoa with intact acrosomes and
membranes than both TCGS low and TCGS high (P = .002). Put together, these
results indicate that the best cryodiluent for rabbit spermatozoa frozen under
the conditions used in this paper is with 7% DMSO and 17% egg yolk in a base
medium containing 25 mM glucose and 25 mM sucrose.
PMID- 28426718
TI - Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in
A/J Min/+ mice.
AB - The International Agency for Research on Cancer has classified red meat as
"probably carcinogenic to humans" (Group 2A). In mechanistic studies exploring
the link between intake of red meat and CRC, heme iron, the pigment of red meat,
is proposed to play a central role as a catalyzer of luminal lipid peroxidation
and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to
investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle
food (dry weight) and 60% powder diet) on Apc-driven intestinal carcinogenesis,
from week 3-13 of age. Muscle food diets did not differentially affect
carcinogenesis in the colon (flat ACF and tumors). In the small intestine, salmon
intake resulted in a lower tumor size and load than did meat from terrestrial
animals (beef, pork or chicken), while no differences were observed between the
effects of white meat (chicken) and red meat (pork and beef). Additional results
indicated that intestinal carcinogenesis was not related to dietary n-6
polyunsaturated fatty acids, intestinal formation of lipid peroxidation products
(thiobarbituric acid reactive substances, TBARS), or cytotoxic effects of fecal
water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to
be relatively low in this study. The greatest tumor load was induced by the
reference diet RM1, underlining the importance of the basic diets in experimental
CRC. The present study in A/J Min/+ mice does not support the hypothesis of a
role of red meat in intestinal carcinogenesis.
PMID- 28426719
TI - Transcriptome of interstitial cells of Cajal reveals unique and selective gene
signatures.
AB - Transcriptome-scale data can reveal essential clues into understanding the
underlying molecular mechanisms behind specific cellular functions and biological
processes. Transcriptomics is a continually growing field of research utilized in
biomarker discovery. The transcriptomic profile of interstitial cells of Cajal
(ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI)
smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow
cytometry, we isolated ICC populations from the murine small intestine and colon
and obtained their transcriptomes. In analyzing the transcriptome, we identified
a unique set of ICC-restricted markers including transcription factors,
epigenetic enzymes/regulators, growth factors, receptors, protein
kinases/phosphatases, and ion channels/transporters. This analysis provides new
and unique insights into the cellular and biological functions of ICC in GI
physiology. Additionally, we constructed an interactive ICC genome browser
(http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To
our knowledge, this is the first online resource that provides a comprehensive
library of all known genetic transcripts expressed in primary ICC. Our genome
browser offers a new perspective into the alternative expression of genes in ICC
and provides a valuable reference for future functional studies.
PMID- 28426720
TI - A new model mimicking persistent HBV e antigen-negative infection using
covalently closed circular DNA in immunocompetent mice.
AB - Despite the availability of an effective vaccine, hepatitis B virus (HBV)
infection remains a major health problem. HBV e antigen (HBeAg)-negative strains
have become prevalent. Previously, no animal model mimicked the clinical course
of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection
model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a
clinical sample and then circularized to form covalently closed circular
(cccDNA). The resulting cccDNA was introduced into the liver of C57BL/6J mice
through hydrodynamic injection. Persistence of the HBeAg-negative infection was
monitored at predetermined time points using HBV-specific markers including HBV
surface antigen (HBsAg), HBeAg, and HBV core antigen (HBcAg) as well as DNA
copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected
with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage.
HBsAg levels increased up to 1 week, at which point levels peaked and dropped
quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more
than 10 weeks. High numbers of HBV DNA copies were detected in the serum and
liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In
contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected
with HBeAg-negative HBV throughout the study period. These results demonstrate
the first successful establishment of a model of HBeAg-negative HBV-persistent
infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the
infection persistence and levels of serum virological and biochemical markers
were approximately equal in the model mice. This model will be useful for
mechanistic studies on HBeAg-negative HBV infection and will facilitate the
evaluation of new antiviral drugs.
PMID- 28426721
TI - Diagnosis, treatment and prognosis of small bowel volvulus in adults: A
monocentric summary of a rare small intestinal obstruction.
AB - OBJECTIVES: Small bowel volvulus is a rare disease, which is also challenging to
diagnose. The aims of this study were to characterize the clinical and
radiological features associated with small bowel volvulus and treatment and to
identify risk factors for associated small bowel necrosis. METHODS: Patients with
small bowel volvulus who underwent operations from January 2001 to December 2015
at the First Affiliated Hospital of China Medical University (Shenyang, China)
were reviewed. Clinical, surgical and postsurgical data were registered and
analyzed. RESULTS: Thirty-one patients were included for analysis. Fifteen
patients were female (48.4%), with an average age of 47.7 years (18-79 years).
The clinical signs and symptoms were unspecific and resembled intestinal
obstruction. Clinical examination revealed abdominal distension and/or diffuse
tenderness with or without signs of peritonitis. The use of CT scans, X-rays or
ultrasound did not differ significantly between patients. In 9 of 20 patients
that received abdominal CT scans, "whirlpool sign" on the CT scan was present.
Secondary small bowel volvulus was present in 58.1% of patients, and causes
included bands (3), adhesion (7), congenital anomalies (7) and stromal tumor (1).
Out of the 31 patients, 15 with gangrenous small bowel had to undergo intestinal
resection. Intestinal gangrene was present with higher neutrophils count
(p<0.0001) and the presence of bloody ascites (p = 0.004). Three patients died of
septic shock (9.68%), and the recurrence rate was 3.23%. CONCLUSIONS: To complete
an early and accurate diagnosis, a CT scan plus physical exam seems to be the
best plan. After diagnosis, an urgent laparotomy must be performed to avoid
intestinal necrosis and perforation. After surgery, more than 90% of the patients
can expect to have a favorable prognosis.
PMID- 28426722
TI - Interactions between mitoNEET and NAF-1 in cells.
AB - The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF
1) are required for cancer cell proliferation and resistance to oxidative stress.
NAF-1 and mNT are also implicated in a number of other human pathologies
including diabetes, neurodegeneration and cardiovascular disease, as well as in
development, differentiation and aging. Previous studies suggested that mNT and
NAF-1 could function in the same pathway in mammalian cells, preventing the over
accumulation of iron and reactive oxygen species (ROS) in mitochondria.
Nevertheless, it is unknown whether these two proteins directly interact in
cells, and how they mediate their function. Here we demonstrate, using yeast two
hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling
analysis (DCA), RNA-sequencing, ROS and iron imaging, and single and double shRNA
lines with suppressed mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1
directly interact in mammalian cells and could function in the same cellular
pathway. We further show using an in vitro cluster transfer assay that mNT can
transfer its clusters to NAF-1. Our study highlights the possibility that mNT and
NAF-1 function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the
levels of iron and Fe-S clusters under control in the mitochondria of mammalian
cells, thereby preventing the activation of apoptosis and/or autophagy and
supporting cellular proliferation.
PMID- 28426723
TI - A decade of arboviral activity-Lessons learned from the trenches.
PMID- 28426724
TI - Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the
Pacific oyster and in silico binding to environmental chemicals.
AB - Disruption of nuclear receptors, a transcription factor superfamily regulating
gene expression in animals, is one proposed mechanism through which pollution
causes effects in aquatic invertebrates. Environmental pollutants have the
ability to interfere with the receptor's functions through direct binding and
inducing incorrect signals. Limited knowledge of invertebrate endocrinology and
molecular regulatory mechanisms, however, impede the understanding of endocrine
disruptive effects in many aquatic invertebrate species. Here, we isolated three
nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the
retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog
CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer
modelling of the receptors based on 3D crystal structures of human proteins was
used to predict each receptor's ability to bind to different ligands in silico.
CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and
the organotin tributyltin (TBT). Computer modelling of CgRAR revealed six
residues in the ligand binding domain, which prevent the successful interaction
with natural and synthetic retinoid ligands. This supports an existing theory of
loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable
due to high discrepancies in sequence to its human ortholog. Yet, there are
suggestions of binding to TBT, but not to rosiglitazone. The effect of potential
receptor ligands on early oyster development was assessed after 24h of chemical
exposure. TBT oxide (0.2MUg/l), all-trans retinoic acid (ATRA) (0.06 mg/L) and
perfluorooctanoic acid (20 mg/L) showed high effects on development (>74%
abnormal developed D-shelled larvae), while rosiglitazone (40 mg/L) showed no
effect. The results are discussed in relation to a putative direct (TBT)
disruption effect on nuclear receptors. The inability of direct binding of ATRA
to CgRAR suggests either a disruptive effect through a pathway excluding nuclear
receptors or an indirect interaction. Our findings provide valuable information
on potential mechanisms of molluscan nuclear receptors and the effects of
environmental pollution on aquatic invertebrates.
PMID- 28426725
TI - Dynamic regulation of Pin1 expression and function during zebrafish development.
AB - The prolyl isomerase Pin1 plays a key role in the modulation of proline-directed
phosphorylation signaling by inducing local conformational changes in
phosphorylated protein substrates. Extensive studies showed different roles for
Pin1 in physiological processes and pathological conditions such as cancer and
neurodegenerative diseases. However, there are still several unanswered questions
regarding its biological role. Notably, despite evidences from cultured cells
showing that Pin1 expression and activity may be regulated by different
mechanisms, little is known on their relevance in vivo. Using Danio rerio
(zebrafish) as a vertebrate model organism we showed that pin1 expression is
regulated during embryogenesis to achieve specific mRNA and protein distribution
patterns. Moreover, we found different subcellular distribution in particular
stages and cell types and we extended the study of Pin1 expression to the adult
zebrafish brain. The analysis of Pin1 overexpression showed alterations on
zebrafish development and the presence of p53-dependent apoptosis. Collectively,
our results suggest that specific mechanisms are operated in different cell types
to regulate Pin1 function.
PMID- 28426726
TI - Vibrotactile stimulation: A non-pharmacological intervention for opioid-exposed
newborns.
AB - OBJECTIVE: To examine the therapeutic potential of stochastic vibrotactile
stimulation (SVS) as a complementary non-pharmacological intervention for
withdrawal in opioid-exposed newborns. STUDY DESIGN: A prospective, within
subjects single-center study was conducted in 26 opioid-exposed newborns (>37
weeks; 16 male) hospitalized since birth and treated pharmacologically for
Neonatal Abstinence Syndrome. A specially-constructed mattress delivered low
level SVS (30-60Hz, 10-12MUm RMS), alternated in 30-min intervals between
continuous vibration (ON) and no vibration (OFF) over a 6-8 hr session. Movement
activity, heart rate, respiratory rate, axillary temperature and blood-oxygen
saturation were calculated separately for ON and OFF. RESULTS: There was a 35%
reduction in movement activity with SVS (p<0.001), with significantly fewer
movement periods >30 sec duration for ON than OFF (p = 0.003). Incidents of
tachypneic breaths and tachycardic heart beats were each significantly reduced
with SVS, whereas incidents of eupneic breaths and eucardic heart beats each
significantly increased with SVS (p<0.03). Infants maintained body temperature
and arterial-blood oxygen level independent of stimulation condition.
CONCLUSIONS: SVS reduced hyperirritability and pathophysiological instabilities
commonly observed in pharmacologically-managed opioid-exposed newborns. SVS may
provide an effective complementary therapeutic intervention for improving
autonomic function in newborns with Neonatal Abstinence Syndrome.
PMID- 28426727
TI - CD4 T-cell expression of IFN-gamma and IL-17 in pediatric malarial anemia.
AB - In Plasmodium falciparum holoendemic transmission regions of western Kenya, life
threatening pediatric malaria manifests primarily as severe malarial anemia (SMA,
Hb<=6.0 g/dL with any density parasitemia). To determine the role that CD4+ T
cell-driven inflammatory responses have in the pathogenesis of SMA, peripheral
CD4+ T-cell populations and their intracellular production of pro-inflammatory
cytokines (IFN-gamma and IL-17) were characterized in children aged 12-36 months
of age stratified into two groups: non-severe malarial anemia (non-SMA, Hb>=6.0
g/dL, n = 50) and SMA (n = 39). In addition, circulating IFN-gamma and IL-17 were
measured as part of a Cytokine 25-plex Antibody Bead Kit, Human (BioSourceTM
International). Children with SMA had higher overall proportions of circulating
lymphocytes (P = 0.003) and elevated proportions of lymphocytes expressing IFN
gamma (P = 0.014) and comparable IL-17 (P = 0.101). In addition, SMA was
characterized by decreased memory-like T-cells (CD4+CD45RA-) expressing IL-17 (P
= 0.009) and lower mean fluorescence intensity in memory-like CD4+ T-cells for
both IFN-gamma (P = 0.063) and IL-17 (P = 0.006). Circulating concentrations of
IFN-gamma were higher in children with SMA (P = 0.009), while IL-17 levels were
comparable between the groups (P = 0.164). Furthermore, circulating levels of IFN
gamma were negatively correlated with IL-17 levels in both groups of children
(SMA: r = -0.610, P = 0.007; and non-SMA: r = -0.516, P = 0.001), while
production of both cytokines by lymphocytes were positively correlated (SMA: r =
0.349, P = 0.037; and non-SMA: r = 0.475, P = 0.001). In addition, this
correlation was only maintained by the memory-like CD4+ T cells (r = 0.365, P =
0.002) but not the naive-like CD4+ T cells. However, circulating levels of IFN
gamma were only associated with naive-like CD4+ T cells producing IFN-gamma (r =
0.547, P = 0.028), while circulating levels of IL-17 were not associated with any
of the cell populations. Taken together, these results suggest that enhanced
severity of malarial anemia is associated with higher overall levels of
circulating lymphocytes, enhanced intracellular production of IFN-gamma by
peripheral lymphocytes and high circulating IFN-gamma levels. In addition, the
observed inverse relationship between the circulating levels of IFN-gamma and IL
17 together with the reduction in the levels of memory-like CD4+ T cells
expressing IL-17 in children with SMA may suggest possible relocation of these
cells in the deeper tissues for their pathological effect.
PMID- 28426728
TI - Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The
MESA Lung Study.
AB - BACKGROUND: Evaluation of impaired left ventricular (LV) filling has focused on
intrinsic causes of LV dysfunction; however, pulmonary vascular changes may
contribute to reduced LV filling and dyspnea. We hypothesized that lower total
pulmonary vascular volume (TPVV) on computed tomography (CT) would be associated
with dyspnea and decrements in LV end-diastolic volume, particularly among ever
smokers. METHODS: The Multi-Ethnic Study of Atherosclerosis recruited adults
without clinical cardiovascular disease in 2000-02. In 2010-12, TPVV was
ascertained as the volume of arteries and veins in the lungs detectable on non
contrast chest CT (vessels >=1 mm diameter). Cardiac measures were assessed by
magnetic resonance imaging (MRI). Dyspnea was self-reported. RESULTS: Of 2303
participants, 53% had ever smoked cigarettes. Among ever-smokers, a lower TPVV
was associated with a lower LV end-diastolic volume (6.9 mL per SD TPVV), stroke
volume, and cardiac output and with dyspnea (all P-values <0.001). Findings were
similar among those without lung disease and those with 0-10 pack-years but were
mostly non-significant among never-smokers. TPVV was associated smaller left
atrial volume but not with LV ejection fraction or MRI measures of impaired LV
relaxation. In a second sample of ever-smokers, a lower pulmonary microvascular
blood volume on contrast-enhanced MRI was also associated with a lower LV end
diastolic volume (P-value = 0.008). CONCLUSION: Reductions in pulmonary vascular
volume were associated with lower LV filling and dyspnea among ever-smokers,
including those without lung disease, suggesting that smoking-related pulmonary
vascular changes may contribute to symptoms and impair cardiac filling and
function without evidence of impaired LV relaxation.
PMID- 28426729
TI - Cultural differences in room size perception.
AB - Cultural differences in spatial perception have been little investigated, which
gives rise to the impression that spatial cognitive processes might be universal.
Contrary to this idea, we demonstrate cultural differences in spatial volume
perception of computer generated rooms between Germans and South Koreans. We used
a psychophysical task in which participants had to judge whether a rectangular
room was larger or smaller than a square room of reference. We systematically
varied the room rectangularity (depth to width aspect ratio) and the viewpoint
(middle of the short wall vs. long wall) from which the room was viewed. South
Koreans were significantly less biased by room rectangularity and viewpoint than
their German counterparts. These results are in line with previous notions of
general cognitive processing strategies being more context dependent in East
Asian societies than Western ones. We point to the necessity of considering
culturally-specific cognitive processing strategies in visual spatial cognition
research.
PMID- 28426730
TI - Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is
associated with hepatocellular carcinoma risk.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant
tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been
identified as a tumor suppressor gene in multiple cancers. We hypothesize that
genetic variations in WWOX are associated with HCC risk. METHODOLOGY/PRINCIPAL
FINDINGS: Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were
evaluated from 708 normal controls and 354 patients with HCC. We identified a
significant association between a WWOX single nucleotide polymorphism (SNP),
rs73569323, and decreased risk of HCC. After adjustment for potential
confounders, patients with at least one T allele at rs11545028 of WWOX may have a
significantly smaller tumor size, reduced levels of alpha-fetoprotein and alanine
aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX
conferred higher risk of vascular invasion. Additional in silico analysis also
suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which
in turn contributes to tumor vascular invasion. CONCLUSIONS: In conclusion,
genetic variations in WWOX may be a significant predictor of early HCC occurrence
and a reliable biomarker for disease progression.
PMID- 28426731
TI - Effect of genetic variation in microRNA binding site in WNT1-inducible signaling
pathway protein 1 gene on oral squamous cell carcinoma susceptibility.
AB - BACKGROUND: Oral squamous cell carcinoma (OSCC), which is the most common head
and neck cancer, accounts for 1%-2% of all human malignancies and is
characterized by poor prognosis and reduced survival rates. WNT1-inducible
signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the
Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental
functions and may be involved in carcinogenesis. This study investigated WISP1
single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and
clinicopathologic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Real-time
polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC
patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970
polymorphism carriers with at least one G allele were susceptible to OSCC.
Moreover, compared with smokers, non-smoker patients with higher frequencies of
WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a
large tumor size. In addition, OSCC patients who were betel quid chewers and
carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node
metastasis. CONCLUSION: Our results demonstrate that a joint effect of WISP1
rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing
causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a
marker or a therapeutic target in OSCC.
PMID- 28426732
TI - Regulation of SESAME-mediated H3T11 phosphorylation by glycolytic enzymes and
metabolites.
AB - Cancer cells prefer aerobic glycolysis, but little is known about the underlying
mechanism. Recent studies showed that the rate-limiting glycolytic enzymes,
pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to
regulate gene expression and cell proliferation, revealing its non-metabolic
functions in connecting glycolysis and histone modifications. We have reported
that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene
expression and oxidative stress resistance. But how glycolysis regulates H3T11
phosphorylation remains unclear. Here, using a series of glycolytic enzyme
mutants and commercial available metabolites, we investigated the role of
glycolytic enzymes and metabolites on H3T11 phosphorylation. Mutation of
glycolytic genes including phosphoglucose isomerase (PGI1), enolase (ENO2),
triosephosphate isomerase (TPI1), or folate biosynthesis enzyme (FOL3)
significantly reduced H3T11 phosphorylation. Further study demonstrated that
glycolysis regulates H3T11 phosphorylation by fueling the substrate,
phosphoenonylpyruvate and the coactivator, FBP to Pyk1. Thus, our results provide
a comprehensive view of how glycolysis modulates H3T11 phosphorylation.
PMID- 28426734
TI - Study of deaths by suicide of homosexual prisoners in Nazi Sachsenhausen
concentration camp.
AB - Living conditions in Nazi concentration camps were harsh and inhumane, leading
many prisoners to commit suicide. Sachsenhausen (Oranienburg, Germany) was a
concentration camp that operated from 1936 to 1945. More than 200,000 people were
detained there under Nazi rule. This study analyzes deaths classified as suicides
by inmates in this camp, classified as homosexuals, both according to the
surviving Nazi files. This collective was especially repressed by the Nazi
authorities. Data was collected from the archives of Sachsenhausen Memorial and
the International Tracing Service in Bad Arolsen. Original death certificates and
autopsy reports were reviewed. Until the end of World War II, there are 14 death
certificates which state "suicide" as cause of death of prisoners classified as
homosexuals, all of them men aged between 23 and 59 years and of various
religions and social strata. Based on a population of 1,200 prisoners classified
as homosexuals, this allows us to calculate a suicide rate of 1,167/100,000 (over
the period of eight years) for this population, a rate 10 times higher than for
global inmates (111/100,000). However, our study has several limitations: not all
suicides are registered; some murders were covered-up as suicides; most documents
were lost during the war or destroyed by the Nazis when leaving the camps and not
much data is available from other camps to compare. We conclude that committing
suicides in Sachsenhausen was a common practice, although accurate data may be
impossible to obtain.
PMID- 28426733
TI - Mini-G proteins: Novel tools for studying GPCRs in their active conformation.
AB - Mini-G proteins are the engineered GTPase domains of Galpha subunits. They couple
to GPCRs and recapitulate the increase in agonist affinity observed upon coupling
of a native heterotrimeric G protein. Given the small size and stability of mini
G proteins, and their ease of expression and purification, they are ideal for
biophysical studies of GPCRs in their fully active state. The first mini-G
protein developed was mini-Gs. Here we extend the family of mini-G proteins to
include mini-Golf, mini-Gi1, mini-Go1 and the chimeras mini-Gs/q and mini-Gs/i.
The mini-G proteins were shown to couple to relevant GPCRs and to form stable
complexes with purified receptors that could be purified by size exclusion
chromatography. Agonist-bound GPCRs coupled to a mini-G protein showed higher
thermal stability compared to the agonist-bound receptor alone. Fusion of GFP at
the N-terminus of mini-G proteins allowed receptor coupling to be monitored by
fluorescence-detection size exclusion chromatography (FSEC) and, in a separate
assay, the affinity of mini-G protein binding to detergent-solubilised receptors
was determined. This work provides the foundation for the development of any mini
G protein and, ultimately, for the structure determination of GPCRs in a fully
active state.
PMID- 28426735
TI - Ten years of Chagas disease research: Looking back to achievements, looking ahead
to challenges.
PMID- 28426736
TI - Lacanobia oleracea nucleopolyhedrovirus (LaolNPV): A new European species of
alphabaculovirus with a narrow host range.
AB - During an insect sampling program in alfalfa crops near Montpellier, France in
2011, Lacanobia oleracea larvae were collected that died due to
nucleopolyhedrovirus infection (LaolNPV). This virus was subjected to molecular
and biological characterization. The virus was a multiple nucleocapsid NPV that
showed similar restriction profiles to Mamestra configurata NPV-A (MacoNPV-A) but
with significant differences. Polypeptide analysis demonstrated similar proteins
in occlusion bodies and occlusion derived virions, to those observed in NPVs from
Mamestra spp. Terminal sequencing revealed that the genome organization shared
similarity with that of MacoNPV-A. The most homologous virus was MacoNPV-A 90/2
isolate (95.63% identity and 96.47% similarity), followed by MacoNPV-A 90/4
strain (95.37% and 96.26%), MacoNPV-B (89.21% and 93.53%) and M. brassicae MNPV
(89.42% and 93.74%). Phylogenetic analysis performed with lef-8, lef-9, polh and
a concatenated set of genes showed that LaolNPV and the Mamestra spp. NPVs
clustered together with HaMNPV, but with a closer genetic distance to MacoNPV-A
strains. The Kimura 2-parameter (K-2-P) distances of the complete genes were
greater than 0.05 between LaolNPV and the MbMNPV/MacoNPV-B/HaMNPV complex, which
indicates that LaolNPV is a distinct species. K-2-P distances were in the range
0.015-0.050 for comparisons of LaolNPV with MacoNPV-A strains, such that
additional biological characteristics should be evaluated to determine species
status. While MacoNPV-A was pathogenic to seven lepidopteran species tested,
LaolNPV was only pathogenic to Chrysodeixis chalcites. Given these findings,
Lacanobia oleracea nucleopolyhedrovirus should be considered as a new species in
the Alphabaculovirus genus.
PMID- 28426737
TI - Incidence and predictors of excessive warfarin anticoagulation in patients with
atrial fibrillation-The EWA study.
AB - Vitamin K antagonist warfarin is widely used in clinical practice and excessive
anticoagulation is a well-known complication of this therapy. Little is known
about permanent and temporary predictors for severe overanticoagulation. The aim
of this study was to investigate the occurrence and predicting factors for
episodes with very high (>=9) international normalized ratio (INR) values in
warfarin treated patients with atrial fibrillation (AF). Excessive Warfarin
Anticoagulation (EWA) study screened all patients (n = 13618) in the Turku
University Hospital region with an INR >=2 between years 2003-2015. Patients
using warfarin anticoagulation for AF with very high (>=9) INR values (EWA Group)
were identified (n = 412 patients) and their characteristics were compared to a
control group (n = 405) of AF patients with stable INR during long-term follow
up. Over 20% (n = 92) of the EWA patients had more than one event of very high
INR and in 105 (25.5%) patients EWA led to a bleeding event. Of the several
temporary and permanent EWA risk factors observed, strongest were excessive
alcohol consumption in 9.6% of patients (OR 24.4, 95% CI 9.9-50.4, p<0.0001) and
reduced renal function (OR 15.2, 95% CI 5.67-40.7, p<0.0001). Recent antibiotic
or antifungal medication, recent hospitalization or outpatient clinic visit and
the first 6 months of warfarin use were the most significant temporary risk
factors for EWA. Excessive warfarin anticoagulation can be predicted with several
permanent and temporary clinical risk factors, many of which are modifiable.
PMID- 28426738
TI - Is antiplatelet treatment effective at attenuating the progression of white
matter hyperintensities?
AB - OBJECTIVE: We performed this study to assess the effect of an antiplatelet agent
on the progression of white matter hyperintensities (WMH). METHODS: From August
2003 to May 2005, we consecutively enrolled patients who underwent brain magnetic
resonance imaging (MRI) for health check-up purposes and showed no significant
findings other than WMH of any degree. Patients were divided into two groups
based on whether or not they received antiplatelet therapy. All patients had a
follow-up brain MRI after 5 years and WMH volume change was measured using
imaging analysis software. To minimize selection bias potentially arising from
antiplatelet treatment assignment, analyses were inverse probability weighted.
RESULTS: Among the 93 patients who met the inclusion criteria, 54 patients
(58.1%) were grouped as the antiplatelet group (AG), and the remaining 39
patients (41.9%) as the non-antiplatelet group (NAG). After inverse propensity
weighting, all baseline characteristics were similar between the two groups, and
antiplatelet treatment did not show any significant effect on the total WMH
volume change (p = 0.957). CONCLUSION: Antiplatelet medication may not alter the
progression of WMH.
PMID- 28426739
TI - Artificial neural network and SARIMA based models for power load forecasting in
Turkish electricity market.
AB - Load information plays an important role in deregulated electricity markets,
since it is the primary factor to make critical decisions on production planning,
day-to-day operations, unit commitment and economic dispatch. Being able to
predict the load for a short term, which covers one hour to a few days, equips
power generation facilities and traders with an advantage. With the deregulation
of electricity markets, a variety of short term load forecasting models are
developed. Deregulation in Turkish Electricity Market has started in 2001 and
liberalization is still in progress with rules being effective in its predefined
schedule. However, there is a very limited number of studies for Turkish Market.
In this study, we introduce two different models for current Turkish Market using
Seasonal Autoregressive Integrated Moving Average (SARIMA) and Artificial Neural
Network (ANN) and present their comparative performances. Building models that
cope with the dynamic nature of deregulated market and are able to run in real
time is the main contribution of this study. We also use our ANN based model to
evaluate the effect of several factors, which are claimed to have effect on
electrical load.
PMID- 28426740
TI - Uncovering the molecular and physiological processes of anticancer leads binding
human serum albumin: A physical insight into drug efficacy.
AB - Human serum albumin (HSA) has its ability to bind drug molecules and influence
their efficacies. Although anticancer leads NSC48693 and NSC290956 functioned at
the same mechanism, the drug efficacies were obviously distinct. To gain insight
into the distinct drug efficacy, the molecular and physiological processes of
anticancer leads binding HSA have been investigated via a combined experimental
and theoretical approach. The binding site, as characterized by fluorescence
quenching and molecular modeling, is found to be located at site II in subdomain
III A for NSC48693 with tight binding and at site FA1 in subdomain I B for
NSC290956 with negatively cooperative binding, respectively. As indicated by the
thermodynamic analysis, NSC48693 binds to HSA with an enthalpy driven mechanism,
while NSC290956 binding with HSA is entropically driven. The further kinetic
analysis indicates that the association rates appear to be similar to these two
anticancer leads, however, the dissociation rate of NSC48693 is approximately 5
fold slower than that of NSC290956. For NSC48693, the pharmacodynamic efficacy is
less than that of NSC290956, while its pharmacokinetic behavior is better than
that of NSC290956. These parameters influence the pharmacodynamic efficacy and
pharmacokinetic behavior, which will give further impacts on drug efficacy in
vivo.
PMID- 28426741
TI - AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal
gene transfers from bacteria to eukaryotes.
AB - Organisms have evolved the ability to tolerate toxic substances in their
environments, often by producing metabolic enzymes that efficiently detoxify the
toxicant. Inorganic arsenic is one of the most toxic and carcinogenic substances
in the environment, but many organisms, including humans, metabolise inorganic
arsenic to less toxic metabolites. This multistep process produces mono-, di-,
and trimethylated arsenic metabolites, which the organism excretes. In humans,
arsenite methyltransferase (AS3MT) appears to be the main metabolic enzyme that
methylates arsenic. In this study, we examined the evolutionary origin of AS3MT
and assessed the ability of different genotypes to produce methylated arsenic
metabolites. Phylogenetic analysis suggests that multiple, independent horizontal
gene transfers between different bacteria, and from bacteria to eukaryotes,
increased tolerance to environmental arsenic during evolution. These findings are
supported by the observation that genetic variation in AS3MT correlates with the
capacity to methylate arsenic. Adaptation to arsenic thus serves as a model for
how organisms evolve to survive under toxic conditions.
PMID- 28426742
TI - Multiple components of PKA and TGF-beta pathways are mutated in pseudomyxoma
peritonei.
AB - Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly
restricted to the peritoneal cavity and most commonly originating from the
appendix. The genetic background of PMP is poorly understood and no targeted
treatments are currently available for this fatal disease. While RAS signaling
pathway is affected in most if not all PMP cases and over half of them also have
a mutation in the GNAS gene, other genetic alterations and affected pathways are,
to a large degree, poorly known. In this study, we sequenced whole coding genome
of nine PMP tumors and paired normal tissues in order to identify additional,
commonly mutated genes and signaling pathways affected in PMP. These exome
sequencing results were validated with an ultra-deep amplicon sequencing method,
leading to 14 validated variants. The validated results contain seven genes that
contribute to the protein kinase A (PKA) pathway. PKA pathway, which also
contains GNAS, is a major player of overproduction of mucin, which is the
characteristic feature of PMP. In addition to PKA pathway, we identified
mutations in six genes that belong to the transforming growth factor beta (TGF
beta) pathway, which is a key regulator of cell proliferation. Since either GNAS
mutation or an alternative mutation in the PKA pathway was identified in 8/9
patients, inhibition of the PKA pathway might reduce mucin production in most of
the PMP patients and potentially suppress disease progression.
PMID- 28426743
TI - Acute kidney injury can predict in-hospital and long-term mortality in elderly
patients undergoing hip fracture surgery.
AB - BACKGROUND: Hip fracture is a common health problem in the elderly that is
associated with increased mortality. Acute kidney injury (AKI) is a frequent
complication in elderly patients undergoing surgery and is associated with the
clinical outcome. We evaluated the incidence and risk factors of AKI in elderly
patients undergoing hip fracture surgery and the impact of AKI on short- and long
term clinical outcomes. METHODS: We performed a retrospective cohort study of 450
elderly patients who underwent hip fracture surgery between January 2010 and
December 2012. We defined AKI according to the Acute Kidney Injury Network (AKIN)
criteria and investigated the effect of AKI on the duration of hospital stay and
in-hospital and long-term mortality. RESULTS: Of the 450 patients, 95 (21.1%)
developed AKI during hospitalization and 178 (39.6%) died, with a mean follow-up
of 3.6 +/- 1.0 years. The baseline serum creatinine level, use of angiotensin
converting enzyme inhibitors or angiotensin-II receptor antagonists, red blood
cell transfusion volume, and history of coronary artery disease were independent
risk factors for AKI. Patients with AKI during hospitalization had significantly
longer hospital stays and higher in-hospital and long-term mortality than those
without AKI. Multivariate analysis revealed that age, history of coronary artery
disease, serum albumin level, and AKI were independent predictors of long-term
mortality. CONCLUSIONS: AKI is a frequent complication in elderly patients
undergoing hip fracture surgery and is independently associated with increased in
hospital and long-term mortality.
PMID- 28426744
TI - Pharmacokinetics and relative bioavailability of an oral amoxicillin-apramycin
combination in pigs.
AB - A new compound granular premix of amoxicillin (20% w/w dry mass)/apramycin (5%
w/w dry mass) was developed, and its pharmacokinetics and relative
bioavailability were determined in pigs following oral administration following a
cross-over study design. The pharmacokinetic parameters of amoxicillin
(t1/2lambda = 6.43 +/- 4.85h, Cmax = 3.2 +/- 1.35 MUg.mL-1, Tmax = 1.92 +/- 0.58,
AUCINF = 8.98 +/- 2.11 h.MUg.mL-1) and apramycin (t1/2lambda = 8.67+/-4.4h, Cmax
= 0.23 +/- 0.12 MUg.mL-1, Tmax = 2.25 +/- 0.82 h, AUCINF = 12.37 +/- 8.64h.MUg.mL
1) when administered as the amoxicillin-apramycin granular premix did not
significantly differ from those for the single-ingredient powder form of each
component. The relative bioavailability of amoxicillin following oral
administration of the amoxicillin-apramycin granular premix was 22.62% when
compared to the intramuscular administration of commercial amoxicillin sodium
powder. This is the first report of a new amoxicillin-apramycin combination which
has a potential veterinary application the for prevention and treatment digestive
tract infections in pigs.
PMID- 28426745
TI - Objective classification of zonular weakness based on lens movement at the start
of capsulorhexis.
AB - PURPOSE: To quantify zonular weakness based on lens movement at the start of
continuous curvilinear capsulorhexis (CCC) and establish a classification system
for it. SETTING: Kozawa Eye Hospital and Diabetes Center, Mito, Japan. DESIGN:
Retrospective interventional case series. METHODS: We examined 402 consecutive
eyes of 316 patients who underwent CCC, phacoemulsification and aspiration (PEA),
and intraocular lens (IOL) implantation. The movement of the lens capsule was
measured using images from video recordings of the CCC procedure. Zonular
weakness was classified based on the shifted distance: Grade I, less than 0.20
mm; Grade II, 0.20-0.39 mm; and Grade III, greater than 0.40 mm. For each of
these grades, we examined the use of the capsule stabilization device during PEA,
the surgical procedure for lens removal, and IOL fixation. RESULTS: We classified
276 eyes (68.6%) as Grade I, 102 eyes (25.4%) as Grade II, and 24 eyes (6.0%) as
Grade III. As the grade increased, the use of the capsule stabilization device in
PEA and scleral suture fixation of IOL increased. CONCLUSIONS: Zonular weakness
was quantified by measuring the movement of the lens capsule. An objective
classification of zonular weakness based on lens movement may be useful for
selecting the appropriate device and procedure during cataract surgery.
PMID- 28426746
TI - Low levels of Cd induce persisting epigenetic modifications and acclimation
mechanisms in the earthworm Lumbricus terrestris.
AB - Toxic effects of cadmium (Cd), a common soil pollutant, are still not very well
understood, particularly in regard to its epigenetic impact. Therefore, the aim
of this study was to assess DNA methylation changes and their persistence in the
earthworm Lumbricus terrestris upon chronic low dose Cd exposure using
methylation sensitive amplification polymorphism (MSAP). Moreover, the biomarker
response and fitness of the earthworms, as well as the expression of
detoxification-related genes (metallothionein (MT) and phytochelatin synthase
(PCS)) was evaluated. Low levels of Cd caused an increase in genome-wide DNA
methylation, which remained partly modified, even after several months of
recovery in unpolluted soil. Increased cellular stress seemed to decrease after
two weeks of exposure whereas fitness parameters remained unaffected by Cd,
probably as a result from the activation of detoxification mechanisms like the
expression of MTs. Interestingly, even though the level of Cd exposure was very
low, MT expression levels indicate the development of acclimation mechanisms.
Taken together, this study demonstrates that acclimation, as well as epigenetic
modifications can occur already in moderately polluted environments. In addition,
these effects can have long-lasting impacts on key species of soil invertebrates
and might persist long after the actual heavy metal challenge has passed.
PMID- 28426748
TI - Tails of the Travelling Gaussian model and the relative age effect: Tales of age
discrimination and wasted talent.
AB - The Relative Age Effect (RAE) documents the inherent disadvantages of being
younger rather than older in an age-banded cohort, typically a school- or
competition-year, to the detriment of career-progression, earnings and wellbeing
into adulthood. We develop the Tails of the Travelling Gaussian (TTG) to model
the mechanisms behind RAE. TTG has notable advantages over existing approaches,
which have been largely descriptive, potentially confounded, and non-comparable
across contexts. In Study 1, using data from the UK's Millennium Cohort Study, we
investigate the different levels of RAE bias across school-level academic
subjects and "personality" traits. Study 2 concerns biased admissions to elite
English Premier League soccer academies, and shows the model can still be used
with minimal data. We also develop two practical metrics: the discrimination
index (ID), to quantify the disadvantages facing cohort-younger children; and the
wastage metric (W), to quantify the loss through untapped potential. TTG is
sufficiently well-specified to simulate the consequences of ID and W for policy
change.
PMID- 28426747
TI - Metabolic analysis of radioresistant medulloblastoma stem-like clones and
potential therapeutic targets.
AB - Medulloblastoma is a fatal brain tumor in children, primarily due to the presence
of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway
is a potential target of cancer therapy because it is often different between
cancer cells and normal cells. However, the metabolic properties of
medulloblastoma stem cells, and whether specific metabolic pathways are essential
for sustaining their stem cell-like phenotype and radioresistance, remain
unclear. We have established radioresistant medulloblastoma stem-like clones
(rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76. Here, we
assessed reactive oxygen species (ROS) production, mitochondria function, oxygen
consumption rate (OCR), energy state, and metabolites of glycolysis and
tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher
lactate production and lower oxygen consumption rate than parental cells.
Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production,
and existed in a low-energy state. Treatment with the metabolic modifier
dichloroacetate (DCA) resulted in mitochondria dysfunction, glycolysis
inhibition, elongated mitochondria morphology, and increased ROS production. DCA
also increased radiosensitivity by suppression of the DNA repair capacity through
nuclear oxidization and accelerated the generation of acetyl CoA to compensate
for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like
characters (e.g., CD133 positivity and sphere-forming ability) in rMSLCs.
Together, our findings provide insights into the specific metabolism of rMSLCs
and illuminate potential metabolic targets that might be exploited for
therapeutic benefit in medulloblastoma.
PMID- 28426749
TI - Molecular characterization, tissue tropism, and genetic variability of the novel
Mupapillomavirus type HPV204 and phylogenetically related types HPV1 and HPV63.
AB - HPV204 is the only newly identified Mupapillomavirus (Mu-PV) type in more than a
decade. To comprehensively characterize HPV204, we performed a detailed molecular
analysis of the viral genome and evaluated its clinical relevance in comparison
to the other Mu-PVs, HPV1 and HPV63. The 7,227-bp long genome of HPV204 exhibits
typical genomic organization of Mu-PVs with eight open reading frames (ORFs) (E6,
E7, E1, E2, E8, E4, L2, and L1). We developed three type-specific quantitative
real-time PCRs and used them to test a representative collection (n = 1,006) of
various HPV-associated benign and malignant neoplasms, as well as samples of
clinically normal cutaneous, mucosal, and mucocutaneous origins. HPV204, HPV1,
and HPV63 were detected in 1.1%, 2.7%, and 1.9% of samples tested, respectively,
and were present in skin and mucosa, suggesting dual tissue tropism of all Mu
PVs. To evaluate the etiological role of Mu-PVs in the development of HPV
associated neoplasms, Mu-PV viral loads per single cell were estimated. HPV1 and
HPV63 were present in high viral copy numbers in 3/43 and 1/43 cutaneous warts,
respectively, and were identified as the most likely causative agents of these
warts. HPV204 viral load was extremely low in a single HPV204-positive cutaneous
wart (7.4 * 10-7 viral copies/cell). Hence, etiological association between
HPV204 and the development of cutaneous warts could not be established. To the
best of our knowledge, this is the first study to evaluate the genetic
variability of Mu-PVs by sequencing complete LCR genomic regions of HPV204, HPV1,
and HPV63. We detected several nucleotide substitutions and deletions within the
LCR genomic regions of Mu-PVs and identified two genetic variants of HPV204 and
HPV63 and five genetic variants of HPV1.
PMID- 28426750
TI - Partnering to promote research where it matters.
PMID- 28426751
TI - The role of microsporidian polar tube protein 4 (PTP4) in host cell infection.
AB - Microsporidia have been identified as pathogens that have important effects on
our health, food security and economy. A key to the success of these obligate
intracellular pathogens is their unique invasion organelle, the polar tube, which
delivers the nucleus containing sporoplasm into host cells during invasion. Due
to the size of the polar tube, the rapidity of polar tube discharge and
sporoplasm passage, and the absence of genetic techniques for the manipulation of
microsporidia, study of this organelle has been difficult and there is relatively
little known regarding polar tube formation and the function of the proteins
making up this structure. Herein, we have characterized polar tube protein 4
(PTP4) from the microsporidium Encephalitozoon hellem and found that a monoclonal
antibody to PTP4 labels the tip of the polar tube suggesting that PTP4 might be
involved in a direct interaction with host cell proteins during invasion. Further
analyses employing indirect immunofluorescence (IFA), enzyme-linked immunosorbent
(ELISA) and fluorescence-activated cell sorting (FACS) assays confirmed that PTP4
binds to mammalian cells. The addition of either recombinant PTP4 protein or anti
PTP4 antibody reduced microsporidian infection of its host cells in vitro.
Proteomic analysis of PTP4 bound to host cell membranes purified by
immunoprecipitation identified transferrin receptor 1 (TfR1) as a potential host
cell interacting partner for PTP4. Additional experiments revealed that knocking
out TfR1, adding TfR1 recombinant protein into cell culture, or adding anti-TfR1
antibody into cell culture significantly reduced microsporidian infection rates.
These results indicate that PTP4 is an important protein competent of the polar
tube involved in the mechanism of host cell infection utilized by these
pathogens.
PMID- 28426753
TI - Correction: A MultiSite Gateway Toolkit for Rapid Cloning of Vertebrate
Expression Constructs with Diverse Research Applications.
AB - [This corrects the article DOI: 10.1371/journal.pone.0159277.].
PMID- 28426752
TI - Somatic copy number alterations in gastric adenocarcinomas among Asian and
Western patients.
AB - Gastric cancer, a leading worldwide cause of cancer mortality, shows high
geographic and ethnic variation in incidence rates, which are highest in East
Asia. The anatomic locations and clinical behavior also differ by geography,
leading to the controversial idea that Eastern and Western forms of the disease
are distinct. In view of these differences, we investigated whether gastric
cancers from Eastern and Western patients show distinct genomic profiles. We used
high-density profiling of somatic copy-number aberrations to analyze the largest
collection to date of gastric adenocarcinomas and utilized genotyping data to
rigorously annotate ethnic status. The size of this collection allowed us to
accurately identify regions of significant copy-number alteration and separately
to evaluate tumors arising in Eastern and Western patients. Among molecular
subtypes classified by The Cancer Genome Atlas, the frequency of gastric cancers
showing chromosomal instability was modestly higher in Western patients. After
accounting for this difference, however, gastric cancers arising in Easterners
and Westerners have highly similar somatic copy-number patterns. Only one genomic
event, focal deletion of the phosphatase gene PTPRD, was significantly enriched
in Western cases, though also detected in Eastern cases. Thus, despite the
different risk factors and clinical features, gastric cancer appears to be a
fundamentally similar disease in both populations and the divergent clinical
outcomes cannot be ascribed to different underlying structural somatic genetic
aberrations.
PMID- 28426754
TI - Assessing environmental attributes and effects of climate change on Sphagnum
peatland distributions in North America using single- and multi-species models.
AB - The fate of Northern peatlands under climate change is important because of their
contribution to global carbon (C) storage. Peatlands are maintained via greater
plant productivity (especially of Sphagnum species) than decomposition, and the
processes involved are strongly mediated by climate. Although some studies
predict that warming will relax constraints on decomposition, leading to
decreased C sequestration, others predict increases in productivity and thus
increases in C sequestration. We explored the lack of congruence between these
predictions using single-species and integrated species distribution models as
proxies for understanding the environmental correlates of North American Sphagnum
peatland occurrence and how projected changes to the environment might influence
these peatlands under climate change. Using Maximum entropy and BIOMOD modelling
platforms, we generated single and integrated species distribution models for
four common Sphagnum species in North America under current climate and a 2050
climate scenario projected by three general circulation models. We evaluated the
environmental correlates of the models and explored the disparities in niche
breadth, niche overlap, and climate suitability among current and future models.
The models consistently show that Sphagnum peatland distribution is influenced by
the balance between soil moisture deficit and temperature of the driest quarter
year. The models identify the east and west coasts of North America as the core
climate space for Sphagnum peatland distribution. The models show that, at least
in the immediate future, the area of suitable climate for Sphagnum peatland could
expand. This result suggests that projected warming would be balanced effectively
by the anticipated increase in precipitation, which would increase Sphagnum
productivity.
PMID- 28426755
TI - Correction: Limbic-thalamo-cortical projections and reward-related circuitry
integrity affects eating behavior: A longitudinal DTI study in adolescents with
restrictive eating disorders.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172129.].
PMID- 28426757
TI - Correction: Community ART Support Groups in Mozambique: The Potential of Patients
as Partners in Care.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166444.].
PMID- 28426756
TI - Excessive dietary intake of vitamin A reduces skull bone thickness in mice.
AB - Calvarial thinning and skull bone defects have been reported in infants with
hypervitaminosis A. These findings have also been described in humans, mice and
zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades
retinoic acid (RA), the active metabolite of vitamin A, indicating that these
effects are indeed caused by too high levels of vitamin A and that evolutionary
conserved mechanisms are involved. To explore these mechanisms, we have fed young
mice excessive doses of vitamin A for one week and then analyzed the skull bones
using micro computed tomography, histomorphometry, histology and
immunohistochemistry. In addition, we have examined the effect of RA on gene
expression in osteoblasts in vitro. Compared to a standard diet, a high dietary
intake of vitamin A resulted in a rapid and significant reduction in calvarial
bone density and suture diastasis. The bone formation rate was almost halved.
There was also increased staining of tartrate resistant acid phosphatase in
osteocytes and an increased perilacunar matrix area, indicating osteocytic
osteolysis. Consistent with this, RA induced genes associated with bone
degradation in osteoblasts in vitro. Moreover, and in contrast to other known
bone resorption stimulators, vitamin A induced osteoclastic bone resorption on
the endocranial surfaces.
PMID- 28426758
TI - Traces of business cycles in credit-rating migrations.
AB - Using migration data of a rating agency, this paper attempts to quantify the
impact of macroeconomic conditions on credit-rating migrations. The migrations
are modeled as a coupled Markov chain, where the macroeconomic factors are
represented by unobserved tendency variables. In the simplest case, these binary
random variables are static and credit-class-specific. A generalization treats
tendency variables evolving as a time-homogeneous Markov chain. A more detailed
analysis assumes a tendency variable for every combination of a credit class and
an industry. The models are tested on a Standard and Poor's (S&P's) dataset.
Parameters are estimated by the maximum likelihood method. According to the
estimates, the investment-grade financial institutions evolve independently of
the rest of the economy represented by the data. This might be an evidence of
implicit too-big-to-fail bail-out guarantee policies of the regulatory
authorities.
PMID- 28426759
TI - Health-related quality of life in South African patients with pulmonary
tuberculosis.
AB - BACKGROUND: The evaluation of patient-reported health-related quality of life
(HRQOL) in pulmonary tuberculosis (TB) contributes to a comprehensive
understanding of the burden associated with this disease. The aim of this study
was to assess the overall impact of TB on the health status and on single health
domains identified in the WHO definition of health, including physical, mental
and social health aspects. METHODS: Four instruments for HRQOL evaluation were
applied in a longitudinal multicentre study during six-month standard TB
treatment in South Africa. These included the generic SF-12 and EQ-5D-5L, the
disease-specific St. George's Respiratory Questionnaire (SGRQ) and the condition
specific Hospital Anxiety and Depression Scale (HADS). Statistical analysis
included significance testing, univariable and multivariable analysis, and
repeated measures ANOVA. Change over time in the physical component score (PCS)
of SF-12 was defined as primary endpoint. A target sample size of 96 patients was
estimated. RESULTS: HRQOL of the study participants was impaired in all physical,
mental and psycho-social health domains at treatment start. HRQOL improved
significantly and in a clinically meaningful manner during the course of standard
TB treatment, over the period of the study. The greatest improvement (95%) was
observed in mental health. Younger patients with higher education and who were
employed had a better HRQOL. DISCUSSION: This study demonstrates the need for an
integrative understanding of TB with HRQOL as core element to inform gaps in
current TB management. Improvements in the management of TB following an
integrative patient-centred approach will contribute towards meeting the United
Nations Sustainable Development Goal 3 (SDG3) target and will support the End TB
strategy of the WHO.
PMID- 28426761
TI - Correction: DHA Supplemented in Peptamen Diet Offers No Advantage in Pathways to
Amyloidosis: Is It Time to Evaluate Composite Lipid Diet?
AB - [This corrects the article DOI: 10.1371/journal.pone.0024094.].
PMID- 28426760
TI - Regulation of proteinaceous effector expression in phytopathogenic fungi.
AB - Effectors are molecules used by microbial pathogens to facilitate infection via
effector-triggered susceptibility or tissue necrosis in their host. Much research
has been focussed on the identification and elucidating the function of fungal
effectors during plant pathogenesis. By comparison, knowledge of how
phytopathogenic fungi regulate the expression of effector genes has been lagging.
Several recent studies have illustrated the role of various transcription
factors, chromosome-based control, effector epistasis, and mobilisation of
endosomes within the fungal hyphae in regulating effector expression and
virulence on the host plant. Improved knowledge of effector regulation is likely
to assist in improving novel crop protection strategies.
PMID- 28426762
TI - Human microRNA-299-3p decreases invasive behavior of cancer cells by
downregulation of Oct4 expression and causes apoptosis.
AB - PURPOSE: Oct4 was reported to be one of the most important pluripotency
transcription factors in the biology of stem cells including cancer stem cells,
and progressed malignant cells. Here we report the investigation of gene
expression control of Oct4 by selected human microRNAs and the physiological
effect of Oct4 silencing in invasive cancer cells. METHODS AND RESULTS: High
throughput luciferase activity assay revealed the microRNA-299-3p to be the most
effective in reducing gene expression of Oct4, which was confirmed by Western
blot analysis and Oct4 promoter activity in a target luciferase assay.
Furthermore, it could be demonstrated that downregulation of Oct4 by microRNAs
299-3p in breast cancer and fibrosarcoma cells lead to a decreased invasiveness
in a microfluidic chip assay. Additionally, microRNA-299-3p causes apoptosis in
cancer cells. Comparison with Oct4 specific siRNA transfection confirmed that
this effect is primary due to the blockade of Oct4 expression. CONCLUSION: The
results suggest that microRNA-299-3p is an interesting target for potential
clinical use. It may be able to decrease invasive behaviour of carcinoma cells;
or even kill these cells by causing apoptosis.
PMID- 28426763
TI - Individual-based modelling of population growth and diffusion in discrete time.
AB - Individual-based models (IBMs) of human populations capture spatio-temporal
dynamics using rules that govern the birth, behavior, and death of individuals.
We explore a stochastic IBM of logistic growth-diffusion with constant time steps
and independent, simultaneous actions of birth, death, and movement that
approaches the Fisher-Kolmogorov model in the continuum limit. This model is well
suited to parallelization on high-performance computers. We explore its emergent
properties with analytical approximations and numerical simulations in parameter
ranges relevant to human population dynamics and ecology, and reproduce
continuous-time results in the limit of small transition probabilities. Our model
prediction indicates that the population density and dispersal speed are affected
by fluctuations in the number of individuals. The discrete-time model displays
novel properties owing to the binomial character of the fluctuations: in certain
regimes of the growth model, a decrease in time step size drives the system away
from the continuum limit. These effects are especially important at local
population sizes of <50 individuals, which largely correspond to group sizes of
hunter-gatherers. As an application scenario, we model the late Pleistocene
dispersal of Homo sapiens into the Americas, and discuss the agreement of model
based estimates of first-arrival dates with archaeological dates in dependence of
IBM model parameter settings.
PMID- 28426764
TI - Structural characterization of core-bradavidin in complex with biotin.
AB - Bradavidin is a tetrameric biotin-binding protein similar to chicken avidin and
bacterial streptavidin, and was originally cloned from the nitrogen-fixing
bacteria Bradyrhizobium diazoefficiens. We have previously reported the crystal
structure of the full-length, wild-type (wt) bradavidin with 138 amino acids,
where the C-terminal residues Gly129-Lys138 ("Brad-tag") act as an intrinsic
ligand (i.e. Gly129-Lys138 bind into the biotin-binding site of an adjacent
subunit within the same tetramer) and has potential as an affinity tag for
biotechnological purposes. Here, the X-ray structure of core-bradavidin lacking
the C-terminal residues Gly114-Lys138, and hence missing the Brad-tag, was
crystallized in complex with biotin at 1.60 A resolution [PDB:4BBO]. We also
report a homology model of rhodavidin, an avidin-like protein from
Rhodopseudomonas palustris, and of an avidin-like protein from Bradyrhizobium sp.
Ai1a-2, both of which have the Brad-tag sequence at their C-terminus. Moreover,
core-bradavidin V1, an engineered variant of the original core-bradavidin, was
also expressed at high levels in E. coli, as well as a double mutant (Cys39Ala
and Cys69Ala) of core-bradavidin (CC mutant). Our data help us to further
engineer the core-bradavidin-Brad-tag pair for biotechnological assays and
chemical biology applications, and provide deeper insight into the biotin-binding
mode of bradavidin.
PMID- 28426765
TI - Allatotropin: A pleiotropic neuropeptide that elicits mosquito immune responses.
AB - Allatotropins (AT) are neuropeptides with pleotropic functions on a variety of
insect tissues. They affect processes such as juvenile hormone biosynthesis,
cardiac rhythm, oviduct and hindgut contractions, nutrient absorption and
circadian cycle. The present work provides experimental evidence that AT elicits
immune responses in two important mosquito disease vectors, Anopheles albimanus
and Aedes aegypti. Hemocytes and an immune-competent mosquito cell line responded
to AT by showing strong morphological changes and increasing bacterial phagocytic
activity. Phenoloxidase activity in hemolymph was also increased in Ae. aegypti
mosquitoes treated with AT but not in An. albimanus, suggesting differences in
the AT-dependent immune activation in the two species. In addition, two important
insect immune markers, nitric oxide levels and expression of antimicrobial
peptide genes, were increased in An. albimanus guts after AT treatment. AT
conjugated to quantum dot nanocrystals (QDots) specifically labeled hemocytes in
vivo in both mosquito species, implying molecular interactions between AT and
hemocytes. The results of our studies suggest a new role for AT in the modulation
of the immune response in mosquitoes.
PMID- 28426766
TI - Activated entomopathogenic nematode infective juveniles release lethal venom
proteins.
AB - Entomopathogenic nematodes (EPNs) are unique parasites due to their symbiosis
with entomopathogenic bacteria and their ability to kill insect hosts quickly
after infection. It is widely believed that EPNs rely on their bacterial partners
for killing hosts. Here we disproved this theory by demonstrating that the in
vitro activated infective juveniles (IJs) of Steinernema carpocapsae (a well
studied EPN species) release venom proteins that are lethal to several insects
including Drosophila melanogaster. We confirmed that the in vitro activation is a
good approximation of the in vivo process by comparing the transcriptomes of
individual in vitro and in vivo activated IJs. We further analyzed the
transcriptomes of non-activated and activated IJs and revealed a dramatic shift
in gene expression during IJ activation. We also analyzed the venom proteome
using mass spectrometry. Among the 472 venom proteins, proteases and protease
inhibitors are especially abundant, and toxin-related proteins such as Shk domain
containing proteins and fatty acid- and retinol-binding proteins are also
detected, which are potential candidates for suppressing the host immune system.
Many of the venom proteins have conserved orthologs in vertebrate-parasitic
nematodes and are differentially expressed during IJ activation, suggesting
conserved functions in nematode parasitism. In summary, our findings strongly
support a new model that S. carpocapsae and likely other Steinernema EPNs have a
more active role in contributing to the pathogenicity of the nematode-bacterium
complex than simply relying on their symbiotic bacteria. Furthermore, we propose
that EPNs are a good model system for investigating vertebrate- and human
parasitic nematodes, especially regarding the function of excretory/secretory
products.
PMID- 28426767
TI - Benign metastasizing leiomyoma: A review of current literature in respect to the
time and type of previous gynecological surgery.
AB - INTRODUCTION: Benign metastasizing leiomyoma (BML) is a rare disorder that
affects women with a history of uterine leiomyoma, which is found to metastasise
within extrauterine sites. The aetiology of BML remains unexplained. Because BML
is rare, and most publications contain descriptions of single cases, no
statistically determined time relations were found between the primary and
secondary surgeries, which may have aetiological implications. OBJECTIVES: To
determine age before BML surgery, age during diagnosis of BML, type of prior
surgery, and location of metastasis based on the literature. METHODS: A
systematic review of four databases (Medline/PubMed, Embase, Web of Science, and
Cochrane) covering articles published from 1 January 1965 to 10 April 2016. The
inclusion criteria were full-text articles in English and articles containing
case reports. Articles in languages other than English (39), articles containing
incomplete data (14), i.e. no information regarding the time of surgery and/or
the site of metastasis, articles bereft of case studies (25), and articles with
access only to summaries, without access to the complete text (10) were excluded.
Of 321 titles identified, only 126 articles met the aforementioned criteria.
RESULTS AND CONCLUSIONS: The mean age during primary surgery and BML diagnosis
was 38.5 years and 47.3 years, respectively. The most common surgery was total
hysterectomy. The most frequent site of metastasis was the lungs; other organs
were affected less frequently.The site of metastases and their number were not
related to the longer time span between the patient's initial surgery and
occurrence of metastasis. The analysed data, such as the age during primary
surgery, age during BML diagnosis, site and type of metastasis, do not provide us
a clear answer. Thus, BML pathogenesis is most probably complex in nature and
requires further multidirectional research.
PMID- 28426768
TI - Abundance of the iron containing biomolecule, heme b, during the progression of a
spring phytoplankton bloom in a mesocosm experiment.
AB - Concentrations of heme b were determined in a mesocosm experiment situated in
Gullmar Fjord off Sweden. The mesocosm experiment lasted for ca. one hundred days
and was characterised by the growth of a primary nutrient replete and a secondary
nutrient deplete phytoplankton bloom. Heme b varied between 40 +/- 10 pmol L-1 in
the prebloom period up to a maximum of 700 +/- 400 pmol L-1 just prior to the
time of the primary chlorophyll a maximum. Thereafter, heme b concentrations
decreased again to an average of 120 +/- 60 pmol L-1. When normalised to total
particulate carbon, heme b was most abundant during the initiation of the
nutrient replete spring bloom, when ratios reached 52 +/- 24 MUmol mol-1; ten
times higher than values observed both pre and post the primary bloom.
Concentrations of heme b correlated with those of chlorophyll a. Nevertheless,
differences were observed in the relative concentrations of the two parameters,
with heme b concentrations increasing relative to chlorophyll a during the growth
of the primary bloom, decreasing over the period of the secondary bloom and
increasing again through the latter period of the experiment. Heme b abundance
was therefore influenced by nutrient concentrations and also likely by changing
community composition. In half of the mesocosms, pCO2 was elevated and maintained
at ca.1000 MUatm, however we observed no significant differences between heme b
in plus or ambient pCO2 mesocosms, either in absolute terms, or relative to total
particulate carbon and chlorophyll a. The results obtained in this study
contribute to our understanding of the distribution of this significant component
of the biogenic iron pool, and provide an iron replete coastal water end member
that aids the interpretation of the distributions of heme b in more iron deplete
open ocean waters.
PMID- 28426769
TI - Examining drivers of the emissions embodied in trade.
AB - Emissions embodied in provincial trade (EEPT) have important effects on
provinces' responsibilities for carbon emission reductions. Based on a multi
regional input-output model, we calculated EEPT for China's 30 provinces in 2002,
2007 and 2010, and we attempted to determine the drivers of EEPT. The results
showed that, during this period, the ratio of EEPT to production-based emissions
increased over time, reaching 40.24% in 2010. In consideration of its important
role in carbon emissions, we analyzed the factors attributable to EEPT through
structure decomposition analysis. The decomposition results showed that final
demand and carbon emission intensity were two major factors in EEPT, while the
final demand in other provinces and the carbon emission intensity in the local
province were major factors for Emissions embodied in provincial exports and the
final demand in the local province and the carbon emission intensity in other
provinces were major factors for Emissions embodied in provincial imports.
Regarding the differences among the EEPT of different provinces, changes in the
structure of trade were the primary reason.
PMID- 28426770
TI - Correction: Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.
AB - [This corrects the article DOI: 10.1371/journal.pone.0159083.].
PMID- 28426771
TI - Correction: A systematic review of rodent pest research in Afro-Malagasy small
holder farming systems: Are we asking the right questions?
AB - [This corrects the article DOI: 10.1371/journal.pone.0174554.].
PMID- 28426772
TI - Correction: Chitosan-propolis nanoparticle formulation demonstrates anti
bacterial activity against Enterococcus faecalis biofilms.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174888.].
PMID- 28426773
TI - Correction: CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours.
AB - [This corrects the article DOI: 10.1371/journal.pone.0149099.].
PMID- 28426774
TI - The role of air pollution in myocardial remodeling.
AB - BACKGROUND: Excessive air pollution in urban environments can impact morbidity
and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in
structural, geometric, and functional remodeling in hearts, using an experimental
model of myocardial infarction. METHODS AND FINDINGS: Seventy-five rats were
divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP),
myocardial infarcted group (MI), infarcted group immediately exposed to pollution
(IGP-I), and infarcted group previously exposed to pollution and kept exposed
after infarction (IGP-II). Greater deposition of interstitial collagen occurred
in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in
controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the
right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP
II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and
IGP-II). At the end of the study, CG had a higher mean shortening fraction than
the other groups had (p<=0.03). Left ventricular systolic diameter was lower in
CG than in infarcted groups (p<=0.003). The infarcted groups had greater
expression of TGF-beta (p<=0.04). PM2.5 increased the expression of TGF-beta in
the IGP-II compared with the MI group (p = 0.004). The TNF-alpha gene was
overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-gamma
gene expression was greater in IGP-II (p<=0.01). Oxidative stress analysis showed
a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I
(p = 0.008) compared with that in CG. CONCLUSIONS: PM2.5 stimulates the
deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted
hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP
II group. It also modulates oxidative stress in healthy hearts but not in
infarcted hearts.
PMID- 28426775
TI - Dynamic behaviors of a modified SIR model in epidemic diseases using nonlinear
incidence and recovery rates.
AB - The transmission of infectious diseases has been studied by mathematical methods
since 1760s, among which SIR model shows its advantage in its epidemiological
description of spread mechanisms. Here we established a modified SIR model with
nonlinear incidence and recovery rates, to understand the influence by any
government intervention and hospitalization condition variation in the spread of
diseases. By analyzing the existence and stability of the equilibria, we found
that the basic reproduction number [Formula: see text] is not a threshold
parameter, and our model undergoes backward bifurcation when there is limited
number of hospital beds. When the saturated coefficient a is set to zero, it is
discovered that the model undergoes the Saddle-Node bifurcation, Hopf
bifurcation, and Bogdanov-Takens bifurcation of codimension 2. The bifurcation
diagram can further be drawn near the cusp type of the Bogdanov-Takens
bifurcation of codimension 3 by numerical simulation. We also found a critical
value of the hospital beds bc at [Formula: see text] and sufficiently small a,
which suggests that the disease can be eliminated at the hospitals where the
number of beds is larger than bc. The same dynamic behaviors exist even when a ?
0. Therefore, it can be concluded that a sufficient number of the beds is
critical to control the epidemic.
PMID- 28426776
TI - Correction: Discovering SIFIs in Interbank Communities.
AB - [This corrects the article DOI: 10.1371/journal.pone.0167781.].
PMID- 28426777
TI - Rotavirus genome replication: Some assembly required.
PMID- 28426778
TI - ApaI polymorphism of vitamin D receptor affects health-related quality of life in
patients with primary sclerosing cholangitis.
AB - BACKGROUND: Polymorphisms of vitamin D receptor (VDR) contribute to the
pathogenesis of multiple autoimmune conditions. METHODS: We investigated the
incidence of VDR polymorphisms (rs1544410-BsmI; rs7975232-ApaI; rs731236-TaqI) in
a group of patients with primary sclerosing cholangitis (PSC, n = 275) and in
healthy controls (n = 376). Additionally, correlations of the VDR polymorphisms
with clinical and biochemical factors of the disease were analysed. RESULTS: The
genotype and allele distributions of these polymorphisms in PSC patients were
similar to those observed in controls. However, the ApaI polymorphism was
associated with an impaired health-related quality of life (HRQoL). The generic
SF-36 questionnaire showed that the Role-Physical (p = 0.01), Role-Emotional (p =
0.01), Physical Component Summary (p = 0.01) and Mental Component Summary (p =
0.003) scores were significantly affected. Similarly, the disease-specific
questionnaires, PBC-40 and PBC-27, demonstrated that carriers of the C allele
suffered from more severe Itch (p = 0.03 assessed by PBC-40 and PBC-27), more
Fatigue (p = 0.02 assessed by PBC-40 and PBC-27) and Impaired Cognitive Capacity
(p = 0.04 and p = 0.03). Correspondingly, individuals who were AA homozygotes
(non-carriers of the C allele of ApaI) had higher summary scores for the Physical
(p = 0.01) and Mental Components (p = 0.006) measured with SF-36. Moreover, they
experienced less itch (p = 0.03) and less Fatigue (p = 0.03) and had better
Cognitive Abilities (p = 0.04) as assessed by the PBC-40 and PBC-27
questionnaires. No associations between other VDR polymorphisms and clinical or
laboratory findings were made. CONCLUSION: In summary, this study is the first to
show that the ApaI polymorphisms in VDR may exert an effect on disease-related
symptoms and quality of life in patients with PSC.
PMID- 28426779
TI - Reference standards for lean mass measures using GE dual energy x-ray
absorptiometry in Caucasian adults.
AB - OBJECTIVE: To develop reference values by age and sex for LM measures using GE
Healthcare DXA systems. METHODS: A de-identified sample was obtained from Ball
State University's Clinical Exercise Physiology Laboratory and University of
Wisconsin-Milwaukee's Physical Activity & Health Research Laboratory. DXA scans
of 2,076 women and 1,251 men were completed using a GE Lunar Prodigy or iDXA.
Percentiles (%ile) were calculated for all variables of interest (LM, LMI, %LM,
and ALMI) and a factorial ANOVA was used to assess differences for each variable
between 10-year age groups and sex, as well as the interaction between age and
sex. RESULTS: Men had higher mean total LM, %LM, LMI, and ALMI than women
(p<0.01), across all age groups. All LM variables decreased significantly over
the 5 decades in men, however in women only total LM, %LM, and ALMI decreased
from the youngest to oldest age groups (p<0.01). CONCLUSION: These reference
values provide for a more accurate interpretation of GE-Healthcare DXA-derived LM
measurements offering clinicians and researchers with an initial resource to aid
in the early detection and assessment of LM deficits.
PMID- 28426780
TI - Response of spatial vegetation distribution in China to climate changes since the
Last Glacial Maximum (LGM).
AB - Analyzing how climate change affects vegetation distribution is one of the
central issues of global change ecology as this has important implications for
the carbon budget of terrestrial vegetation. Mapping vegetation distribution
under historical climate scenarios is essential for understanding the response of
vegetation distribution to future climatic changes. The reconstructions of
palaeovegetation based on pollen data provide a useful method to understand the
relationship between climate and vegetation distribution. However, this method is
limited in time and space. Here, using species distribution model (SDM)
approaches, we explored the climatic determinants of contemporary vegetation
distribution and reconstructed the distribution of Chinese vegetation during the
Last Glacial Maximum (LGM, 18,000 14C yr BP) and Middle-Holocene (MH, 6000 14C yr
BP). The dynamics of vegetation distribution since the LGM reconstructed by SDMs
were largely consistent with those based on pollen data, suggesting that the SDM
approach is a useful tool for studying historical vegetation dynamics and its
response to climate change across time and space. Comparison between the modeled
contemporary potential natural vegetation distribution and the observed
contemporary distribution suggests that temperate deciduous forests, subtropical
evergreen broadleaf forests, temperate deciduous shrublands and temperate steppe
have low range fillings and are strongly influenced by human activities. In
general, the Tibetan Plateau, North and Northeast China, and the areas near the
30 degrees N in Central and Southeast China appeared to have experienced the
highest turnover in vegetation due to climate change from the LGM to the present.
PMID- 28426781
TI - Tauroursodeoxycholic acid (TUDCA) attenuates pressure overload-induced cardiac
remodeling by reducing endoplasmic reticulum stress.
AB - Pressure overload in the heart induces pathological hypertrophy and is associated
with cardiac dysfunction. Apoptosis and fibrosis signaling initiated by the
endoplasmic reticulum stress (ERS) is known to contribute to these maladaptive
effects. The aim of this study was to investigate whether reduction of ERS by a
known chemical chaperone, tauroursodeoxycholic acid (TUDCA) can attenuate
pressure overload-induced cardiac remodeling in a mouse model of transverse
aortic constriction (TAC). Oral administration of TUDCA at a dose of 300 mg/kg
body weight (BW) in the TUDCA-TAC group reduced ERS markers (GRP78, p-PERK, and p
eIf2alpha), compared to the Vehicle (Veh)-TAC group. TUDCA administration, for 4
weeks after TAC significantly reduced cardiac hypertrophy as shown by the reduced
heart weight (HW) to BW ratio, and expression of hypertrophic marker genes (ANF,
BNP, and alpha-SKA). Masson's trichrome staining showed that myocardial fibrosis
and collagen deposition were also significantly reduced in the TUDCA-TAC group.
We also found that TUDCA significantly decreased expression of TGF-beta signaling
proteins and collagen isoforms. TUDCA administration also reduced cardiac
apoptosis and the related proteins in the TUDCA-TAC group. Microarray analysis
followed by gene ontology (GO) and pathway analysis demonstrated that
extracellular matrix genes responsible for hypertrophy and fibrosis, and
mitochondrial genes responsible for apoptosis and fatty acid metabolism were
significantly altered in the Veh-TAC group, but the alterations were normalized
in the TUDCA-TAC group, suggesting potential of TUDCA in treatment of heart
diseases related to pressure-overload.
PMID- 28426782
TI - Peste des petits ruminants (PPR): A neglected tropical disease in Maghreb region
of North Africa and its threat to Europe.
AB - BACKGROUND: Peste des petits ruminants (PPR) is a contagious disease listed by
the World Organisation for Animal health (OIE) as being a specific hazard. It
affects sheep, goats, and wild ungulates, and is prevalent throughout the
developing world particularly Asia, the Middle East, and Africa. PPR has been
targeted for eradication by 2030 by the Food and Agriculture Organization of the
United Nations (FAO) and the OIE, after the successful eradication of the related
disease, rinderpest in cattle. PPR was first reported in 1942 in the Ivory Coast
in Western Africa and has since extended its range in Asia, the Middle East, and
Africa posing an immediate threat of incursion into Europe, South East Asia and
South Africa. Although robust vaccines are available, the use of these vaccines
in a systematic and rational manner is not widespread, resulting in this
devastating disease becoming an important neglected tropical disease in the
developing world. METHODOLOGY: We isolated and characterized the PPR virus from
an outbreak in Cheraga, northern Algeria, during October 2015 by analyzing the
partial N-gene sequence in comparison with other viruses from the Maghreb region.
As well as sequencing the full length viral genome and performing real-time RT
PCR on clinical samples. Maximum-likelihood and Bayesian temporal and
phylogeographic analyses were performed to assess the persistence and spread of
PPRV circulation from Eastern Africa in the Maghreb region of North Africa.
CONCLUSIONS: Recent PPR outbreaks in Cheraga, in the northern part of Algiers
(October 2015) and North-West Morocco (June, 2015) highlight that PPRV has spread
to the northern border of North Africa and may pose a threat of introduction to
Europe. Phylogeographic analysis suggests that lineage IV PPRV has spread from
Eastern Africa, most likely from the Sudan 2000 outbreak, into Northern Africa
resulting in the 2008 Moroccan outbreak. Maximum-likelihood and Bayesian analysis
shows that these North African viruses cluster closely together suggesting the
existence of continual regional circulation. Considering the same virus is
circulating in Algeria, Morocco and Tunisia, implementation of a common Maghreb
PPR eradication strategy would be beneficial for the region.
PMID- 28426783
TI - Correction: Kinetics and Muscle Activity Patterns during Unweighting and
Reloading Transition Phases in Running.
AB - [This corrects the article DOI: 10.1371/journal.pone.0168545.].
PMID- 28426784
TI - Building on the success of soil-transmitted helminth control - The future of
deworming.
PMID- 28426785
TI - Genome-wide association studies identified multiple genetic loci for body size at
four growth stages in Chinese Holstein cattle.
AB - The growth and maturity of cattle body size affect not only feed efficiency, but
also productivity and longevity. Dissecting the genetic architecture of body size
is critical for cattle breeding to improve both efficiency and productivity. The
volume and weight of body size are indicated by several measurements. Among them,
Heart Girth (HG) and Hip Height (HH) are the most important traits. They are
widely used as predictors of body weight (BW). Few association studies have been
conducted for HG and HH in cattle focusing on single growth stage. In this study,
we extended the Genome-wide association studies to a full spectrum of four growth
stages (6-, 12-, 18-, and 24-months after birth) in Chinese Holstein heifers. The
whole genomic single nucleotide polymorphisms (SNPs) were obtained from the
Illumina BovineSNP50 v2 BeadChip genotyped on 3,325 individuals. Estimated
breeding values (EBVs) were derived for both HG and HH at the four different ages
and analyzed separately for GWAS by using the Fixed and random model Circuitous
Probability Unification (FarmCPU) method. In total, 27 SNPs were identified to be
significantly associated with HG and HH at different growth stages. We found 66
candidate genes located nearby the associated SNPs, including nine genes that
were known as highly related to development and skeletal and muscular growth. In
addition, biological function analysis was performed by Ingenuity Pathway
Analysis and an interaction network related to development was obtained, which
contained 16 genes out of the 66 candidates. The set of putative genes provided
valuable resources and can help elucidate the genomic architecture and mechanisms
underlying growth traits in dairy cattle.
PMID- 28426787
TI - Correction: Treatment with Riluzole Restores Normal Control of Soleus and
Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic
Nerve Crush at Birth.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170235.].
PMID- 28426786
TI - T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration
in an osteoarthritis disease model.
AB - Osteoarthritis (OA) is one of the most common diseases affecting older people;
however, there remains no effective targeted drug to combat OA. The aims of this
study were (1) to explore the effect of T140 in regulating degeneration of
articular cartilage in vivo by targeted blocking of the SDF-1/CXCR4 signaling
pathway, and (2) to provide experimental evidence for the development of a novel
OA-targeted pharmacotherapy. Thirty-six healthy Hartley guinea pigs were randomly
divided into three groups: a T140-treated group (n = 12), a phosphate buffer
saline control group (n = 12) and an untreated control group (n = 12). At 2, 4,
6, 8, 10 and 12 weeks of treatment, SDF-1 in serum was quantified by enzyme
linked immunosorbent assay. At 12 weeks of treatment, the cartilage from knee
tibial plateau in the knee joint was collected for H&E, Safranin-O staining and
Mankin grading; measurement for mRNA levels of matrix metalloproteinases (MMP-3,
MMP-9 and MMP-13), aggrecan (ACAN) and collagen II (Col II) using RT-PCR; and
measurement for Col II protein levels by western blot. Results showed that SDF-1
in serum increased in the T140 group and increased in the control groups. H&E and
Safranin-O staining revealed less cartilage loss in T140-treated animals compared
to controls. The mRNA levels of MMP-3, MMP-9 and MMP-13 in cartilage were much
lower in the T140 group than other groups, but mRNA levels of ACAN and Col II in
cartilage were higher in the T140-treated group. Col II protein levels in the
T140 group and control groups were different. T140 can downregulate the
expression of matrix-degrading enzyme and lessen the degeneration of cartilage by
blocking the SDF-1/CRCR4 signaling pathway in vivo. This mechanism may present a
pharmacological target for the treatment of OA.
PMID- 28426788
TI - Association between hemoglobin glycation index with insulin resistance and
carotid atherosclerosis in non-diabetic individuals.
AB - Hemoglobin glycation index (HGI), defined as the difference between the observed
HbA1c value and the value of HbA1c predicted from plasma glucose levels,
represents a measure of the degree of non-enzymatic glycation of hemoglobin and
it has been found to be positively associated with micro- and macro-vascular
complications in subjects with type 2 diabetes. To investigate the
pathophysiological abnormalities responsible for the increased cardiovascular
risk of patients with higher HGI, we evaluated the association of HGI with cardio
metabolic characteristics in nondiabetic offspring of type 2 diabetic
individuals. Insulin sensitivity, measured by a hyperinsulinemic-euglycemic
clamp, cardio-metabolic risk factors including lipid profile, uric acid and
inflammatory factors, and ultrasound measurement of carotid intima-media
thickness (IMT) were assessed in 387 nondiabetic individuals. Participants were
stratified in tertiles according to HGI (high, moderate and low). As compared
with subjects with low HGI, those with high HGI displayed an unfavorable cardio
metabolic risk profile having significantly higher values of BMI, waist
circumference, triglycerides, uric acid, fasting insulin, inflammatory markers,
such as high sensitivity C reactive protein, erythrocytes sedimentation rate,
complement C3, fibrinogen, and white blood cell count, and carotid IMT, and lower
HDL and insulin-stimulated glucose disposal. In a linear regression analysis
model including several atherosclerotic risk factors such as gender, age, BMI,
inflammatory factors, lipid profile, insulin-stimulated glucose disposal, fasting
insulin, uric acid, and blood pressure, HGI was the major predictor of IMT (beta
= 0.35; P = 0.001). In a logistic regression analysis adjusted for confounders,
individuals with high HGI showed a 2.7-fold increased risk of vascular
atherosclerosis (OR 2.72, 95%CI 1.01-7.37) as compared with subjects with low
HGI. The present findings support the notion that HGI may be a useful tool to
identify a subset of nondiabetic individuals conceivably harboring a higher risk
of cardiovascular disease.
PMID- 28426789
TI - Gre factors-mediated control of hilD transcription is essential for the invasion
of epithelial cells by Salmonella enterica serovar Typhimurium.
AB - The invasion of epithelial cells by Salmonella enterica serovar Typhimurium is a
very tightly regulated process. Signaling cascades triggered by different
environmental and physiological signals converge to control HilD, an AraC
regulator that coordinates the expression of several virulence factors. The
expression of hilD is modulated at several steps of the expression process. Here,
we report that the invasion of epithelial cells by S. Typhimurium strains lacking
the Gre factors, GreA and GreB, is impaired. By interacting with the RNA
polymerase secondary channel, the Gre factors prevent backtracking of paused
complexes to avoid arrest during transcriptional elongation. Our results indicate
that the Gre factors are required for the expression of the bacterial factors
needed for epithelial cell invasion by modulating expression of HilD. This
regulation does not occur at transcription initiation and depends on the capacity
of the Gre factors to prevent backtracking of the RNA polymerase. Remarkably,
genetic analyses indicate that the 3'-untranslated region (UTR) of hilD is
required for Gre-mediated regulation of hilD expression. Our data provide new
insight into the complex regulation of S. Typhimurium virulence and highlight the
role of the hilD 3'-UTR as a regulatory motif.
PMID- 28426791
TI - Correction: CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target
Prediction Tool.
AB - [This corrects the article DOI: 10.1371/journal.pone.0124633.].
PMID- 28426790
TI - Lethality of mice bearing a knockout of the Ngly1-gene is partially rescued by
the additional deletion of the Engase gene.
AB - The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating
enzyme that is highly conserved among eukaryotes. It was recently reported that
subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms
(NGLY1-deficiency). While the enzyme obviously has a critical role in mammals,
its precise function remains unclear. In this study, we analyzed Ngly1-deficient
mice and found that they are embryonic lethal in C57BL/6 background.
Surprisingly, the additional deletion of the gene encoding endo-beta-N
acetylglucosaminidase (Engase), which is another de-N-glycosylating enzyme but
leaves a single GlcNAc at glycosylated Asn residues, resulted in the partial
rescue of the lethality of the Ngly1-deficient mice. Additionally, we also found
that a change in the genetic background of C57BL/6 mice, produced by crossing the
mice with an outbred mouse strain (ICR) could partially rescue the embryonic
lethality of Ngly1-deficient mice. Viable Ngly1-deficient mice in a C57BL/6 and
ICR mixed background, however, showed a very severe phenotype reminiscent of the
symptoms of NGLY1-deficiency subjects. Again, many of those defects were strongly
suppressed by the additional deletion of Engase in the C57BL/6 and ICR mixed
background. The defects observed in Ngly1/Engase-deficient mice (C57BL/6
background) and Ngly1-deficient mice (C57BL/6 and ICR mixed background) closely
resembled some of the symptoms of patients with an NGLY1-deficiency. These
observations strongly suggest that the Ngly1- or Ngly1/Engase-deficient mice
could serve as a valuable animal model for studies related to the pathogenesis of
the NGLY1-deficiency, and that cytoplasmic ENGase represents one of the potential
therapeutic targets for this genetic disorder.
PMID- 28426792
TI - No evidence for the radiation time lag model after whole genome duplications in
Teleostei.
AB - The short and long term effects of polyploidization on the evolutionary fate of
lineages is still unclear despite much interest. First recognized in land plants,
it has become clear that polyploidization is widespread in eukaryotes, notably at
the origin of vertebrates and teleost fishes. Many hypotheses have been proposed
to link the species richness of lineages and whole genome duplications. For
instance, the radiation time lag model suggests that paleopolyploidy would favour
the apparition of new phenotypic traits, although the radiation of the lineage
would not occur before a later dispersion event. Some results indicate that this
model may be observed during land plant evolution. In this work, we test
predictions of the radiation time lag model using both fossil data and molecular
phylogenies in ancient and more recent teleost whole genome duplications. We fail
to find any evidence of delayed increase of the species number after any of these
events and conclude that paleopolyploidization still remains to be unambiguously
linked to taxonomic diversity in teleosts.
PMID- 28426793
TI - Prevalence of cardiovascular medication on secondary prevention after myocardial
infarction in China between 1995-2015: A systematic review and meta-analysis.
AB - BACKGROUND: Myocardial Infarction (MI) has become a major cause of morbidity and
mortality in China, but little is known about the prevalence of guideline
recommended cardiovascular medications after MI events over the last two decades.
This systematic review and meta-analysis aims to summarize cardiovascular
medication use between 1995-2015 and to assess factors in associated with the
trends in cardiovascular medications. METHOD: A systematic search was conducted
in four databases (Pubmed, Embase, CENTRAL, and CNKI) to obtain observational
studies published between 1995 and 2015, reporting on the use of cardiovascular
medications in China. Risk of bias of individual studies was appraised and
selected studies were pooled for estimated prevalence of cardiovascular
medication. Prevalence of cardiovascular medication use for 1995 and 2015 was
estimated by random effects meta-regression model. RESULTS: From 13,940
identified publications, 35 studies, comprising 28,000 patients, were included.
The pooled prevalence for aspirin, beta-blockers, statins, ACE-Inhibitors, ACE
Inhibitor/ARBs and nitrates was 92% [95% confidence interval (CI): 0.89-0.95],
63% (95% CI: 0.57-0.69), 72% (95% CI: 0.60-0.82), 49% (95% CI: 0.41-0.57), 59%
(95% CI: 0.48-0.69) and 79% (95% CI: 0.74-0.91), respectively. A significant
increase in beta-blocker and statin use and a decrease of nitrate use was
observed over time. The estimated prevalence of beta-blockers, statins, and
nitrates was 78%, 91.1%, and 59.3% in 2015, compared to 32%, 17% and 96% in 1995,
respectively. CONCLUSION: Cardiovascular medication use after MI is far from
optimal in Chinese patients, even though the prevalence of use increased over the
period 1995-2015. With a rapidly increasing number of MI patients in China, a
comprehensive strategy on secondary prevention is warranted. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO (CRD42015025246).
PMID- 28426794
TI - Impact of Wolbachia on oxidative stress sensitivity in the parasitic wasp Asobara
japonica.
AB - The oxidative homeostasis is the balance between reactive oxygen species and
antioxidant molecules. In addition to be considered as a key factor underlying
life-history traits evolution, the oxidative homeostasis has been shown to be
involved in many host-symbiont associations. Previous studies suggest an
interaction between the bacterial endosymbiont Wolbachia and the oxidative
homeostasis of some insect hosts. This interaction is likely to exert a strong
influence on the host evolution, as it has been proposed in the wasp Asobara
tabida, whose dependence upon Wolbachia is due to the evolutionary loss of its
ability to regulate the oxidative homeostasis in the absence of the symbiont.
Although such cases of complete dependence are rare, cases of insects having lost
only a part of their autonomy over the control of the oxidative homeostasis might
be more common. If so, one can expect that insects having coevolved with
Wolbachia will be more sensitive to oxidative stress when cured of their
symbionts. We tested this hypothesis by studying the effects of an experimentally
induced oxidative stress on various life-history traits of Asobara japonica, a
species closely related to A. tabida. For most of the life-history traits
studied, the sensitivity of the wasps to oxidative stress did not correlate with
their infection status. The only exception was the parasitic success. However,
contrarily to our expectation, the sensitivity to oxidative stress was increased,
rather than decreased, when Wolbachia was present. This result suggests that
Wolbachia does not participate to mitigate oxidative stress in A. japonica, and
that on the contrary its presence might still be costly in stressful
environments.
PMID- 28426795
TI - Properties of healthcare teaming networks as a function of network construction
algorithms.
AB - Network models of healthcare systems can be used to examine how providers
collaborate, communicate, refer patients to each other, and to map how patients
traverse the network of providers. Most healthcare service network models have
been constructed from patient claims data, using billing claims to link a patient
with a specific provider in time. The data sets can be quite large (106-108
individual claims per year), making standard methods for network construction
computationally challenging and thus requiring the use of alternate construction
algorithms. While these alternate methods have seen increasing use in generating
healthcare networks, there is little to no literature comparing the differences
in the structural properties of the generated networks, which as we demonstrate,
can be dramatically different. To address this issue, we compared the properties
of healthcare networks constructed using different algorithms from 2013 Medicare
Part B outpatient claims data. Three different algorithms were compared: binning,
sliding frame, and trace-route. Unipartite networks linking either providers or
healthcare organizations by shared patients were built using each method. We find
that each algorithm produced networks with substantially different topological
properties, as reflected by numbers of edges, network density, assortativity,
clustering coefficients and other structural measures. Provider networks adhered
to a power law, while organization networks were best fit by a power law with
exponential cutoff. Censoring networks to exclude edges with less than 11 shared
patients, a common de-identification practice for healthcare network data,
markedly reduced edge numbers and network density, and greatly altered measures
of vertex prominence such as the betweenness centrality. Data analysis identified
patterns in the distance patients travel between network providers, and a
striking set of teaming relationships between providers in the Northeast United
States and Florida, likely due to seasonal residence patterns of Medicare
beneficiaries. We conclude that the choice of network construction algorithm is
critical for healthcare network analysis, and discuss the implications of our
findings for selecting the algorithm best suited to the type of analysis to be
performed.
PMID- 28426796
TI - Correction: Side Effects in Time Discounting Procedures: Fixed Alternatives
Become the Reference Point.
AB - [This corrects the article DOI: 10.1371/journal.pone.0165245.].
PMID- 28426797
TI - Is bilingualism losing its advantage? A bibliometric approach.
AB - This study uses several bibliometric indices to explore the temporal course of
publication trends regarding the bilingual advantage in executive control over a
ten-year window. These indices include the number of published papers, numbers of
citations, and the journal impact factor. According to the information available
in their abstracts, studies were classified into one of four categories:
supporting, ambiguous towards, not mentioning, or challenging the bilingual
advantage. Results show that the number of papers challenging the bilingual
advantage increased notably in 2014 and 2015. Both the average impact factor and
the accumulated citations as of June 2016 were equivalent between categories.
However, of the studies published in 2014, those that challenge the bilingual
advantage accumulated more citations in June 2016 than those supporting it. Our
findings offer evidence-based bibliometric information about the current state of
the literature and suggest a change in publication trends regarding the
literature on the bilingual advantage.
PMID- 28426798
TI - Glucotoxicity induces abnormal glucagon secretion through impaired insulin
signaling in InR1G cells.
AB - The significance of glucagon in the pathophysiology of diabetes mellitus is
widely recognized, but the mechanisms underlying dysregulated glucagon secretion
are still unclear. Here, we explored the molecular mechanisms of glucagon
dysregulation, using an in vitro model. Hamster-derived glucagon-secreting InR1G
cells were exposed to high glucose (25 mM) levels for 12 h before analyzing
glucagon secretion and the activity of components involved in insulin signaling.
High-glucose treatment induced increased glucagon secretion in InR1G cells, which
represents a hallmark of diabetes mellitus. This treatment reduced the
phosphorylation of Akt, indicating the deterioration of insulin signaling.
Simultaneously, oxidative stress and JNK activity were shown to be increased. The
inhibition of JNK signaling resulted in the amelioration of high-glucose level
induced glucagon secretion. Abnormally elevated glucagon secretion in diabetes
can be reproduced by high-glucose treatment of InR1G cells, and the involvement
of high glucose-oxidative stress-JNK-insulin signaling pathway axis has been
demonstrated. These data elucidate, at least partly, the previously unclear
mechanism of abnormal glucagon secretion, providing insights into a potential
novel approach to diabetes treatment, targeting glucagon.
PMID- 28426799
TI - Cell cycle profiling by image and flow cytometry: The optimised protocol for the
detection of replicational activity using 5-Bromo-2'-deoxyuridine, low
concentration of hydrochloric acid and exonuclease III.
AB - The approach for the detection of replicational activity in cells using 5-bromo
2'-deoxyuridine, a low concentration of hydrochloric acid and exonuclease III is
presented in the study. The described method was optimised with the aim to
provide a fast and robust tool for the detection of DNA synthesis with minimal
impact on the cellular structures using image and flow cytometry. The approach is
based on the introduction of breaks into the DNA by the low concentration of
hydrochloric acid followed by the subsequent enzymatic extension of these breaks
using exonuclease III. Our data showed that the method has only a minimal effect
on the tested protein localisations and is applicable both for formaldehyde- and
ethanol-fixed cells. The approach partially also preserves the fluorescence of
the fluorescent proteins in the HeLa cells expressing Fluorescent Ubiquitin Cell
Cycle Indicator. In the case of the short labelling pulses that disabled the use
of 5-ethynyl-2'-deoxyuridine because of the low specific signal, the described
method provided a bright signal enabling reliable recognition of replicating
cells. The optimized protocol was also successfully tested for the detection of
trifluridine, the nucleoside used as an antiviral drug and in combination with
tipiracil also for the treatment of some types of cancer.
PMID- 28426800
TI - Neutrophil-lymphocyte ratio predicts short term mortality in patients with
hepatitis B virus-related acute-on-chronic liver failure treated with an
artificial liver support system.
AB - AIM: Hepatitis B virus-related acute-on-chronic liver failure has high short-term
mortality. Artificial liver support systems (ALSS) may improve outcome and avoid
liver transplantation, but predicting short-term prognosis in such patients is
difficult. This study aimed to determine whether the neutrophil-lymphocyte ratio
(NLR), an inflammation marker, predicted mortality in patients treated with ALSS.
METHODS: A total of 560 patients with hepatitis B virus-related acute-on-chronic
liver failure were enrolled, 338 were treated with ALSS and the others treated
with standard of care(SOC). Clinical variables and the NLR were evaluated for
prognostic value. RESULTS: Thirty-day mortality was 28.4% in ALSS and 55.4% in
SOC patients. The NLR was lower in survivors than in ALSS or SOC patients who
died. Univariate and multivariate analysis found that NLR and the chronic liver
failure sequential organ failure assessment scores(CLIF-SOFA) were independently
associated with 30-day mortality. Among patients with NLRs <= 3, 3-6, and >6, 30
day mortality was 7.7%,23.1%, and 69.2% in ALSS and 25.5%, 50.0%, and 75.0% in
SOC patients. Among patients with NLRs <= 3 or 3-6, mortality was lower in ALSS
than in SOC patients (P < 0.01). Mortality rates of ALSS and SOC patients with
NLRs > 6 did not different (P >0.05). The area under curve of NLR and CLIF-SOFA
was 0.82 and 0.88 in ALSS group, 0.78 and 0.86 in SOC group. The results suggest
that liver function in most patients with NLRs <= 3 recovered with ALSS
treatment, and patients with NLRs > 6 needed emergency liver transplantation.
CONCLUSION: NLR was an independent predictor of mortality in ALSS patients and
may assist physicians in determining treatment options.
PMID- 28426801
TI - The change of serum tumor necrosis factor alpha in patients with type 1 diabetes
mellitus: A systematic review and meta-analysis.
AB - OBJECTIVE: The aim of this study was used meta-analysis to investigate changes of
serum tumor necrosis factor-alpha (TNF-alpha) in patients with type 1 diabetes
mellitus (T1DM). METHODS: Relevant literatures were identified from PubMed,
Cochrane Library, CNKI, WanFang and Chinese-Cqvip databases (published from
January 1, 1999 to September 30, 2016). Eligible reports were included for pooled
analysis of serum TNF-alpha level and subgroup analysis was performed in relation
with age, disease duration and ethnicity. RESULTS: A total of 23 articles (1631
T1DM cases, 1429 healthy controls) were included for this meta-analysis. Compared
with the controls, the patients had significantly increased serum TNF-alpha level
(P < 0.001). Similar results were also found among all subgroup analysis of
different age, disease duration and ethnicity (with the exception of Asian) (all
P < 0.05). Regression analysis indicated that age (P = 0.680), disease duration
(P = 0.957), and ethnicity (P = 0.526) of patients were not significant impact
factors for the high heterogeneity. The results were stable according to the
sensitivity analysis and no publication bias existed in this meta-analysis.
CONCLUSIONS: Serum TNF-alpha level in T1DM patients has significantly elevated
among all age, disease duration and ethnicity groups.
PMID- 28426802
TI - Decoding the infant mind: Multivariate pattern analysis (MVPA) using fNIRS.
AB - The MRI environment restricts the types of populations and tasks that can be
studied by cognitive neuroscientists (e.g., young infants, face-to-face
communication). FNIRS is a neuroimaging modality that records the same
physiological signal as fMRI but without the constraints of MRI, and with better
spatial localization than EEG. However, research in the fNIRS community largely
lacks the analytic sophistication of analogous fMRI work, restricting the
application of this imaging technology. The current paper presents a method of
multivariate pattern analysis for fNIRS that allows the authors to decode the
infant mind (a key fNIRS population). Specifically, multivariate pattern analysis
(MVPA) employs a correlation-based decoding method where a group model is
constructed for all infants except one; both average patterns (i.e., infant
level) and single trial patterns (i.e., trial-level) of activation are decoded.
Between subjects decoding is a particularly difficult task, because each infant
has their own somewhat idiosyncratic patterns of neural activation. The fact that
our method succeeds at across-subject decoding demonstrates the presence of group
level multi-channel regularities across infants. The code for implementing these
analyses has been made readily available online to facilitate the quick adoption
of this method to advance the methodological tools available to the fNIRS
researcher.
PMID- 28426803
TI - Dendritic cell maturation, but not type I interferon exposure, restricts
infection by HTLV-1, and viral transmission to T-cells.
AB - Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T
cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic
Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with
HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously
demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1
infection than autologous primary T-cells, suggesting that DC infection precedes
T-cell infection. However, during blood transmission, breast-feeding or sexual
transmission, HTLV-1 may encounter different DC subsets present in the blood, the
intestinal or genital mucosa respectively. These different contacts may impact
HTLV-1 ability to infect DCs and its subsequent transfer to T-cells. Using in
vitro monocyte-derived IL-4 DCs, TGF-beta DCs and IFN-alpha DCs that mimic DCs
contacting HTLV-1 in vivo, we show here that despite their increased ability to
capture HTLV-1 virions, IFN-alpha DCs restrict HTLV-1 productive infection.
Surprisingly, we then demonstrate that it is not due to the antiviral activity of
type-I interferon produced by IFN-alpha DCs, but that it is likely to be linked
to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-alpha DCs. Finally,
we demonstrate that, in contrast to IL-4 DCs, IFN-alpha DCs are impaired in their
capacity to transfer HTLV-1 to CD4 T-cells, both after viral capture and trans
infection and after their productive infection. In conclusion, the nature of the
DCs encountered by HTLV-1 upon primo-infection and the viral trafficking route
through the vesicular pathway of these cells determine the efficiency of viral
transmission to T-cells, which may condition the fate of infection.
PMID- 28426804
TI - DNA damage induces expression of WWP1 to target DeltaNp63alpha to degradation.
AB - DeltaNp63alphaplays key roles in cell survival and proliferation. So its
expression is always tightly controlled in cells. We previously reported that DNA
damage down-regulates transcription of DeltaNp63alphain FaDu and HaCat cells,
which contributes to cell apoptosis. In the present study, we found that DNA
damage induces down-regulation of DeltaNp63alphavia facilitating its proteasomal
degradation in cell lines such as MDA-MB-231 and MCF10A. Further investigation
revealed that transcription of WWP1 is stimulated by DNA damage in these cells.
Knock-down of WWP1 abrogates DNA damage-induced down-regulation of
DeltaNp63alphaand partially rescues cell apoptosis. Interestingly, DNA damage may
stimulate WWP1 through different mechanisms in different cell types: it up
regulates transcription of WWP1 in a p53-dependent manner in MCF10A and HEK293
cells, while miR-452 may be involved in DNA damage-induced up-regulation of WWP1
in MDA-MB-231 cells. Our study demonstrates a novel pathway which regulates
DeltaNp63alphaupon cellular response to chemotherapeutic agents.
PMID- 28426805
TI - Evidence of horizontal gene transfer by transposase gene analyses in
Fervidobacterium species.
AB - Horizontal Gene Transfer (HGT) plays an important role in the physiology and
evolution of microorganisms above all thermophilic prokaryotes. Some members of
the Phylum Thermotogae (i.e., Thermotoga spp.) have been reported to present
genomes constituted by a mosaic of genes from a variety of origins. This study
presents a novel approach to search on the potential plasticity of
Fervidobacterium genomes using putative transposase-encoding genes as the target
of analysis. Transposases are key proteins involved in genomic DNA
rearrangements. A comprehensive comparative analysis, including phylogeny, non
metric multidimensional scaling analysis of tetranucleotide frequencies,
repetitive flanking sequences and divergence estimates, was performed on the
transposase genes detected in four Fervidobacterium genomes: F. nodosum, F.
pennivorans, F. islandicum and a new isolate (Fervidobacterium sp. FC2004).
Transposase sequences were classified in different groups by their degree of
similarity. The different methods used in this study pointed that over half of
the transposase genes represented putative HGT events with closest relative
sequences within the phylum Firmicutes, being Caldicellulosiruptor the genus
showing highest gene sequence proximity. These results confirmed a direct
evolutionary relationship through HGT between specific Fervidobacterium species
and thermophilic Firmicutes leading to potential gene sequence and functionality
sharing to thrive under similar environmental conditions. Transposase-encoding
genes represent suitable targets to approach the plasticity and potential
mosaicism of bacterial genomes.
PMID- 28426807
TI - Correction: Risk factors associated with sexually transmitted infections among
HIV infected men who have sex with men.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170635.].
PMID- 28426806
TI - The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein
family, shows similarity to type III secretion chaperones but suggests different
cellular functions.
AB - AmyR is a stress and virulence associated protein from the plant pathogenic
Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved
ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora
AmyR reveals a class I type III secretion chaperone-like fold, despite the lack
of sequence similarity between these two classes of protein and lacking any
evidence of a secretion-associated role. The results indicate that AmyR, and YbjN
proteins in general, function through protein-protein interactions without any
enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low
sequence similarity with other members of the YbjN protein family in Eubacteria,
yet a high level of structural conservation is observed. Across the YbjN protein
family sequence conservation is limited to residues stabilising the protein core
and dimerization interface, while interacting regions are only conserved between
closely related species. This study presents the first structure of a YbjN
protein from Enterobacteriaceae, the most highly divergent and well-studied
subgroup of YbjN proteins, and an in-depth sequence and structural analysis of
this important but poorly understood protein family.
PMID- 28426808
TI - A screen for protective drugs against delayed hypoxic injury.
AB - Despite longstanding efforts to develop cytoprotective drugs against
ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to
treat hypoxic injury. The failure of traditional strategies at solving this
problem suggests the need for novel and unbiased approaches that can lead to
previously unsuspected targets and lead compounds. Towards this end, we report
here a unique small molecule screen in the nematode C. elegans for compounds that
improve recovery when applied after the hypoxic insult, using a C. elegans strain
engineered to have delayed cell non-autonomous death. In a screen of 2000
compounds, six were found to produce significant protection of C. elegans from
delayed death. Four of the compounds were tested in an ex vivo mouse heart
ischemia/reperfusion model and two, meclocycline and 3-amino-1,2,4-triazole,
significantly reduced infarction size. Our work demonstrates the feasibility of
this novel C. elegans screen to discover hypoxia protective drugs that are also
protective in a mammalian model of hypoxic injury.
PMID- 28426809
TI - Denaturation of proteins by surfactants studied by the Taylor dispersion
analysis.
AB - We showed that the Taylor Dispersion Analysis (TDA) is a fast and easy to use
method for the study of denaturation proteins. We applied TDA to study
denaturation of beta-lactoglobulin, transferrin, and human insulin by anionic
surfactant sodium dodecyl sulfate (SDS). A series of measurements at constant
protein concentration (for transferrin was 1.9 x 10-5 M, for beta- lactoglobulin
was 7.6 x 10-5 M, and for insulin was 1.2 x 10-4 M) and varying SDS
concentrations were carried out in the phosphate-buffered saline (PBS). The
structural changes were analyzed based on the diffusion coefficients of the
complexes formed at various surfactant concentrations. The concentration of
surfactant was varied in the range from 1.2 x 10-4 M to 8.7 x 10-2 M. We
determined the minimum concentration of the surfactant necessary to change the
native conformation of the proteins. The minimal concentration of SDS for beta
lactoglobulin and transferrin was 4.3 x 10-4 M and for insulin 2.3 x 10-4 M. To
evaluate the TDA as a novel method for studying denaturation of proteins we also
applied other methods i.e. electronic circular dichroism (ECD) and dynamic light
scattering (DLS) to study the same phenomenon. The results obtained using these
methods were in agreement with the results from TDA.
PMID- 28426810
TI - Correction: miRNAs in the vitreous humor of patients affected by idiopathic
epiretinal membrane and macular hole.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174297.].
PMID- 28426811
TI - Procalcitonin for selecting the antibiotic regimen in outpatients with low-risk
community-acquired pneumonia using a rapid point-of-care testing: A single-arm
clinical trial.
AB - OBJECTIVE: We aimed to assess the role of procalcitonin (PCT) to guide the
initial selection of the antibiotic regimen for low-risk community-acquired
pneumonia (CAP). METHODS: A single-arm clinical trial was conducted including
outpatients with CAP and Pneumonia Severity Index risk classes I-II.
Antimicrobial selection was based on the results of PCT measured with a rapid
point-of-care testing. According to serum PCT levels, patients were assigned to
two treatment strategies: oral azithromycin if PCT was <0.5 ng/ml, or
levofloxacin if levels were >=0.5 ng/ml. Primary outcome was clinical cure rate.
Short-term and long-term outcomes were assessed. Results were compared with those
of a historical standard-of-care control-group treated in our centre. RESULTS: Of
253 subjects included, 216 (85.4%) were assigned to azithromycin. Pneumococcal
infection was diagnosed in 26 (12%) and 21 (56.8%) patients allocated to
azithromycin and levofloxacin groups, respectively. No patients in the
azithromycin group developed bacteraemia. Atypical organisms were more common in
patients given azithromycin (18.5% vs 8.1%, respectively). The majority (93%) of
patients with atypical pneumonia had low PCT levels. Clinical cure rates were
95.8% in the azithromycin group, 94.6% in the levofloxacin group, and 94.4% in
the historical control group. No 30-day mortality or recurrences were observed,
and the 3-year rates of recurrence and mortality were very low in both groups.
Adverse events occurrence was also infrequent. CONCLUSION: A PCT-guided strategy
with a rapid point-of-care testing safely allowed selecting empirical narrow
spectrum antibiotics in outpatients with CAP. TRIAL REGISTRATION: The study is
registered with ClinicalTrials.gov, number NCT02600806.
PMID- 28426812
TI - Religion and the public ethics of stem-cell research: Attitudes in Europe, Canada
and the United States.
AB - We examine international public opinion towards stem-cell research during the
period when the issue was at its most contentious. We draw upon representative
sample surveys in Europe and North America, fielded in 2005 and find that the
majority of people in Europe, Canada and the United States supported stem-cell
research, providing it was tightly regulated, but that there were key differences
between the geographical regions in the relative importance of different types of
ethical position. In the U.S., moral acceptability was more influential as a
driver of support for stem-cell research; in Europe the perceived benefit to
society carried more weight; and in Canada the two were almost equally important.
We also find that public opinion on stem-cell research was more strongly
associated with religious convictions in the U.S. than in Canada and Europe,
although many strongly religious citizens in all regions approved of stem-cell
research. We conclude that if anything public opinion or 'public ethics' are
likely to play an increasingly important role in framing policy and regulatory
regimes for sensitive technologies in the future.
PMID- 28426813
TI - Correction: Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves
reduces colon cancer growth and induces caspase-dependent apoptosis in colon
cancer cells via the mitochondrial apoptotic pathway.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170823.].
PMID- 28426814
TI - Progress and projections in the program to eliminate trachoma.
PMID- 28426815
TI - Using controlled attenuation parameter combined with ultrasound to survey non
alcoholic fatty liver disease in hemodialysis patients: A prospective cohort
study.
AB - BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a non-invasive
method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease
(NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the
leading cause of morbidity and mortality in hemodialysis patients. The aim of
this study was to investigate the prevalence of NAFLD in hemodialysis patients.
METHOD: We prospectively enrolled patients undergoing chronic hemodialysis, as
well as patients with normal renal function who served as controls. The control
group patients were referred by an endocrinologist to be tested for NAFLD; most
of these patients had diabetes, hypertension, or dyslipidemia. We excluded those
with excess alcohol intake, use of drugs known to induce HS, chronic viral
hepatitis, or CAP failure. CAP >= 238 dB/m was used as a cutoff suggesting HS. An
increased liver kidney contrast, as defined by ultrasound, was used to make the
diagnosis of HS. RESULTS: Three hundred and forty-three hemodialysis patients and
252 control group patients were enrolled. Among the hemodialysis patients, 192
(56.0%) had CAP- or ultrasound-identified HS compared with 91 (26.5%) who only
had ultrasound-identified HS (P<0.001). Among the control group patients, 212
(84.1%) had CAP- or ultrasound-identified HS compared with 180 (71.4%) who only
had ultrasound-identified HS (P<0.001). CONCLUSIONS: The prevalence of NAFLD in
the hemodialysis patients was 56%. The number of diagnoses of NAFLD made by using
CAP combined with ultrasound was more than 2 times the number made with
ultrasound alone in the hemodialysis patients. Therefore, we suggest the use of
CAP combined with ultrasound to screen for NAFLD in hemodialysis patients.
PMID- 28426816
TI - Ex vivo cultures combined with vivo-morpholino induced gene knockdown provide a
system to assess the role of WT1 and GATA4 during gonad differentiation.
AB - Gonad morphogenesis relies on the correct spatiotemporal expression of a number
of genes that together fulfill the differentiation of the bipotential gonad into
testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal
for proper gonadal development. Here we address the contributions of GATA4 and
WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo
technique for cultivating gonads in hanging droplets of media that were
supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in
combination at the same developmental stage. We show that WT1 is equally
important for both, the initial establishment and the maintenance of the sex
specific gene expression signature in testes and ovaries. We further identified
Foxl2 as a novel putative downstream target gene of WT1. Moreover, knockdown of
WT1 reduced mRNA levels of several molecular components of the hedgehog signaling
pathway in XY gonads, whereas Gata4 vivo-morpholino treatment increased
transcripts of Dhh and Ptch1 in embryonic testes. The data suggest that for its
proper function, WT1 relies on the correct expression of the GATA4 protein.
Furthermore, GATA4 down-regulates several ovarian promoting genes in testes, such
as Ctnnb1, Fst, and Bmp2, suggesting that this repression is required for
maintaining the male phenotype. In conclusion, this study provides novel insights
into the role of WT1 and GATA4 during the sex differentiation phase and
represents an approach that can be applied to assess other proteins with as yet
unknown functions during gonadal development.
PMID- 28426817
TI - Evaluation of machine learning algorithms and structural features for optimal MRI
based diagnostic prediction in psychosis.
AB - A relatively large number of studies have investigated the power of structural
magnetic resonance imaging (sMRI) data to discriminate patients with
schizophrenia from healthy controls. However, very few of them have also included
patients with bipolar disorder, allowing the clinically relevant discrimination
between both psychotic diagnostics. To assess the efficacy of sMRI data for
diagnostic prediction in psychosis we objectively evaluated the discriminative
power of a wide range of commonly used machine learning algorithms (ridge, lasso,
elastic net and L0 norm regularized logistic regressions, a support vector
classifier, regularized discriminant analysis, random forests and a Gaussian
process classifier) on main sMRI features including grey and white matter voxel
based morphometry (VBM), vertex-based cortical thickness and volume, region of
interest volumetric measures and wavelet-based morphometry (WBM) maps. All
possible combinations of algorithms and data features were considered in pairwise
classifications of matched samples of healthy controls (N = 127), patients with
schizophrenia (N = 128) and patients with bipolar disorder (N = 128). Results
show that the selection of feature type is important, with grey matter VBM
(without data reduction) delivering the best diagnostic prediction rates
(averaging over classifiers: schizophrenia vs. healthy 75%, bipolar disorder vs.
healthy 63% and schizophrenia vs. bipolar disorder 62%) whereas algorithms
usually yielded very similar results. Indeed, those grey matter VBM accuracy
rates were not even improved by combining all feature types in a single
prediction model. Further multi-class classifications considering the three
groups simultaneously made evident a lack of predictive power for the bipolar
group, probably due to its intermediate anatomical features, located between
those observed in healthy controls and those found in patients with
schizophrenia. Finally, we provide MRIPredict
(https://www.nitrc.org/projects/mripredict/), a free tool for SPM, FSL and R, to
easily carry out voxelwise predictions based on VBM images.
PMID- 28426818
TI - Alternative glacial-interglacial refugia demographic hypotheses tested on
Cephalocereus columna-trajani (Cactaceae) in the intertropical Mexican drylands.
AB - Historic demography changes of plant species adapted to New World arid
environments could be consistent with either the Glacial Refugium Hypothesis
(GRH), which posits that populations contracted to refuges during the cold-dry
glacial and expanded in warm-humid interglacial periods, or with the Interglacial
Refugium Hypothesis (IRH), which suggests that populations contracted during
interglacials and expanded in glacial times. These contrasting hypotheses are
developed in the present study for the giant columnar cactus Cephalocereus
columna-trajani in the intertropical Mexican drylands where the effects of Late
Quaternary climatic changes on phylogeography of cacti remain largely unknown. In
order to determine if the historic demography and phylogeographic structure of
the species are consistent with either hypothesis, sequences of the chloroplast
regions psbA-trnH and trnT-trnL from 110 individuals from 10 populations
comprising the full distribution range of this species were analysed. Standard
estimators of genetic diversity and structure were calculated. The historic
demography was analysed using a Bayesian approach and the palaeodistribution was
derived from ecological niche modelling to determine if, in the arid environments
of south-central Mexico, glacial-interglacial cycles drove the genetic divergence
and diversification of this species. Results reveal low but statistically
significant population differentiation (FST = 0.124, P < 0.001), although very
clear geographic clusters are not formed. Genetic diversity, haplotype network
and Approximate Bayesian Computation (ABC) demographic analyses suggest a
population expansion estimated to have taken place in the Last Interglacial
(123.04 kya, 95% CI 115.3-130.03). The species palaeodistribution is consistent
with the ABC analyses and indicates that the potential area of palaedistribution
and climatic suitability were larger during the Last Interglacial and Holocene
than in the Last Glacial Maximum. Overall, these results suggest that C. columna
trajani experienced an expansion following the warm conditions of interglacials,
in accordance with the GRH.
PMID- 28426820
TI - The influence of cell membrane and SNAP25 linker loop on the dynamics and
unzipping of SNARE complex.
AB - The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
complex is composed of three neuronal proteins VAMP2, Syntaxin and SNAP25, which
plays a core role during the process of membrane fusion. The zipping assembly of
the SNARE complex releases energies and drives the vesicle and cell membrane into
close proximity. In this study, we use all-atom molecular dynamics simulations to
probe the dynamics of SNARE and its unzipping process in the context of membrane
at the atomistic details. Our results indicated that the NTD of SNARE core domain
is relatively more stable than CTD, which is in agreement with previous
experiments. More importantly, possible interactions between the linker loop (LL)
region of SNAP25 and VAMP2 are observed, suggests that the LL region may
facilitate VAMP2 binding and SNARE initiation. The forced unzipping of SNARE in
the presence of membrane and LL of SNAP25 reveals the possible pathway for energy
generation of SNARE zipping, provides information to understand how force may
regulate the cooperativity between the membrane and the SNARE complex.
PMID- 28426819
TI - Virological success after 12 and 24 months of antiretroviral therapy in sub
Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies
using a systematic review and meta-analysis.
AB - BACKGROUND: UNAIDS recently defined the 90-90-90 target as a way to end the HIV
epidemic. However, the proportion of virological success following antiretroviral
therapy (ART) may not be as high as the anticipated 90%, and may in fact be
highly heterogeneous. We aimed to describe the proportion of virological success
in sub-Saharan Africa and to identify factors associated with the proportion of
virological success. METHODS: We performed a systematic review and meta-analysis
focusing on the proportion of patients in sub-Saharan Africa who demonstrate
virological success at 12 and 24 months since ART initiation, as well as at 6 and
36 months, where possible. Programme factors associated with the proportion of
virological success were identified using meta-regression. Analyses were
conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches.
RESULTS: Eighty-five articles were included in the meta-analysis, corresponding
to 125 independent study populations. Using an on-treatment approach, the
proportions (95% confidence interval (CI)) of virological success at 12 (n = 64)
and at 24 (n = 32) months since ART initiation were 87.7% (81.3-91.0) and 83.7%
(79.8-87.6), respectively. Univariate analysis indicated that the proportion of
virological success was not different by study design. Multivariate analysis at
24 months showed that the proportion of virological success was significantly
larger in studies conducted in public sector sites than in other sites (p =
0.045). Using an ITT approach, the proportions (95% CI) of virological success at
12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8-69.1) and 56.8% (51.3
62.4), respectively. At 12 months, multivariate analysis showed that the
proportion of success was significantly lower in cohort studies than in trials
(63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that
the proportion of success was also lower in cohorts. DISCUSSION: Regardless of
the time following ART initiation, and of the threshold, proportions of
virological success were highly variable. Evidence from this review suggests that
the new international target of 90% of patients controlled is not yet being
achieved, and that in order to improve the virological outcome, efforts should be
made to improve retention in care.
PMID- 28426821
TI - The importance of model systems: Why we study a virus on the brink of global
eradication.
PMID- 28426822
TI - Genomics of a revived breed: Case study of the Belgian campine cattle.
AB - Through centuries of both natural and artificial selection, a variety of local
cattle populations arose with highly specific phenotypes. However, the
intensification and expansion of scale in animal production systems led to the
predominance of a few highly productive cattle breeds. The loss of local
populations is often considered irreversible and with them specific qualities and
rare variants could be lost as well. Over these last years, the interest in these
local breeds has increased again leading to increasing efforts to conserve these
breeds or even revive lost populations, e.g. through the use of crosses with
similar breeds. However, the remaining populations are expected to contain
crossbred individuals resulting from introgressions. They are likely to carry
exogenous genes that affect the breed's authenticity on a genomic level. Using
the revived Campine breed as a case study, 289 individuals registered as
purebreds were genotyped on the Illumina BovineSNP50. In addition, genomic
information on the Illumina BovineHD and Illumina BovineSNP50 of ten breeds was
available to assess the current population structure, genetic diversity, and
introgression with phenotypically similar and/or historically related breeds.
Introgression with Holstein and beef cattle genotypes was limited to only a few
farms. While the current population shows a substantial amount of within-breed
variation, the majority of genotypes can be separated from other breeds in the
study, supporting the re-establishment of the Campine breed. The majority of the
population is genetically close to the Deep Red (NL), Improved Red (NL) and
Eastern Belgium Red and White (BE) cattle, breeds known for their historical ties
to the Campine breed. This would support an open herdbook policy, thereby
increasing the population size and consequently providing a more secure future
for the breed.
PMID- 28426823
TI - Observation of sigma-pore currents in mutant hKv1.2_V370C potassium channels.
AB - Current through the sigma-pore was first detected in hKv1.3_V388C channels, where
the V388C mutation in hKv1.3 channels opened a new pathway (sigma-pore) behind
the central alpha-pore. Typical for this mutant channel was inward current at
potentials more negative than -100 mV when the central alpha-pore was closed. The
alpha-pore blockers such as TEA+ and peptide toxins (CTX, MTX) could not reduce
current through the sigma-pore of hKv1.3_V388C channels. This new pathway would
proceed in parallel to the alpha-pore in the S6-S6 interface gap. To see whether
this phenomenon is restricted to hKv1.3 channels we mutated hKv1.2 at the
homologue position (hKv1.2_V370C). By overexpression of hKv1.2_V370C mutant
channels in COS-7 cells we could show typical sigma-currents. The
electrophysiological properties of the sigma-pore in hKv1.3_V388C and
hKv1.2_V370C mutant channels were similar. The sigma-pore of hKv1.2_V370C
channels was most permeable to Na+ and Li+ whereas Cl- and protons did not
influence current through the sigma-pore. Tetraethylammonium (TEA+),
charybdotoxin (CTX) and maurotoxin (MTX), known alpha-pore blockers, could not
reduce current through the sigma-pore of hKv1.2_V370C channels. Taken together we
conclude that the observation of sigma-pore currents is not restricted to Kv1.3
potassium channels but can also be observed in a closely related potassium
channel. This finding could have implications in the treatment of different ion
channel diseases linked to mutations of the respective channels in regions close
to homologue position investigated by us.
PMID- 28426824
TI - Becoming more oneself? Changes in personality following DBS treatment for
psychiatric disorders: Experiences of OCD patients and general considerations.
AB - Does DBS change a patient's personality? This is one of the central questions in
the debate on the ethics of treatment with Deep Brain Stimulation (DBS). At the
moment, however, this important debate is hampered by the fact that there is
relatively little data available concerning what patients actually experience
following DBS treatment. There are a few qualitative studies with patients with
Parkinson's disease and Primary Dystonia and some case reports, but there has
been no qualitative study yet with patients suffering from psychiatric disorders.
In this paper, we present the experiences of 18 patients with Obsessive
Compulsive Disorder (OCD) who are undergoing treatment with DBS. We will also
discuss the inherent difficulties of how to define and assess changes in
personality, in particular for patients with psychiatric disorders. We end with a
discussion of the data and how these shed new light on the conceptual debate
about how to define personality.
PMID- 28426825
TI - Levels of HIV-1 persistence on antiretroviral therapy are not associated with
markers of inflammation or activation.
AB - Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but
both can persist despite clinically effective ART. The relationships among pre
ART and on-ART levels of HIV-1 and activation are incompletely understood, in
part because prior studies have been small or cross-sectional. To address these
limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell
activation and T cell cycling in a longitudinal cohort of 101 participants who
initiated ART and had well-documented sustained suppression of plasma viremia for
a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA
declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525
fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per
year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA
RNA before starting treatment had higher levels while on ART, despite suppression
of plasma viremia for many years. Markers of inflammation and T cell activation
were associated with plasma HIV-1 RNA levels before ART was initiated but there
were no consistent associations between these markers and HIV-1 DNA or CA-RNA
during long-term ART, suggesting that HIV-1 persistence is not driving or driven
by inflammation or activation. Higher levels of inflammation, T cell activation
and cycling before ART were associated with higher levels during ART, indicating
that immunologic events that occurred well before ART initiation had long-lasting
effects despite sustained virologic suppression. These findings should stimulate
studies of viral and host factors that affect virologic, inflammatory and
immunologic set points prior to ART initiation and should inform the design of
strategies to reduce HIV-1 reservoirs and dampen immune activation that persists
despite ART.
PMID- 28426826
TI - Link-prediction to tackle the boundary specification problem in social network
surveys.
AB - Diffusion processes in social networks often cause the emergence of global
phenomena from individual behavior within a society. The study of those global
phenomena and the simulation of those diffusion processes frequently require a
good model of the global network. However, survey data and data from online
sources are often restricted to single social groups or features, such as age
groups, single schools, companies, or interest groups. Hence, a modeling approach
is required that extrapolates the locally restricted data to a global network
model. We tackle this Missing Data Problem using Link-Prediction techniques from
social network research, network generation techniques from the area of Social
Simulation, as well as a combination of both. We found that techniques employing
less information may be more adequate to solve this problem, especially when data
granularity is an issue. We validated the network models created with our
techniques on a number of real-world networks, investigating degree distributions
as well as the likelihood of links given the geographical distance between two
nodes.
PMID- 28426827
TI - Correction: Helicobacter pylori bab Paralog Distribution and Association with
cagA, vacA, and homA/B Genotypes in American and South Korean Clinical Isolates.
AB - [This corrects the article DOI: 10.1371/journal.pone.0137078.].
PMID- 28426828
TI - Consumption of fortified infant foods reduces dietary diversity but has a
positive effect on subsequent growth in infants from Sumedang district,
Indonesia.
AB - Stunting and underweight among under-five children in Indonesia are common,
raising public health concerns. Whether inappropriate complementary feeding (CF)
practices compromise optimal growth during late infancy in Indonesia is
uncertain. Therefore we characterized and evaluated CF practices in Indonesian
infants and investigated their relationship with subsequent growth. We enrolled
breastfed infants at 6 months of age (n = 230); and followed them at 9 (n = 202)
and 12 months of age (n = 190). We collected socio-demographic and anthropometric
data and two-day in-home weighed food records. Relations between WHO CF
indicators, sentinel foods, and energy and micronutrient intakes at 9 months and
growth at 12 months were explored using multiple linear regression. Stunting and
underweight increased from 15.8% and 4.4% at 6 months to 22.6% and 10.5% at 12
months, respectively. Median intakes of calcium, iron, zinc, and riboflavin were
below WHO recommendations. Infants consuming fortified infant foods (FIFs) at 9
months had diets with a lower dietary diversity (DD) score (2.3 vs.3.0), energy
density, median energy (250 vs. 310 kcal/d) and protein (6.5 vs. 9.1 g/d) intake
than non-consumers (p<0.01), despite higher intakes of calcium, iron, and
vitamins A and C (p<0.001). Positive relations existed for 9-month consumption of
iron-rich/iron fortified infant foods with length-for-age Z-score (LAZ) at 12
months (beta = 0.22; 95% CI: 0.01, 0.44; P = 0.04), and for fortified infant
foods alone with both LAZ (beta = 0.29; 95% CI: 0.09, 0.48; P = 0.04) and weight
for-age Z-score (beta = 0.14; 95% CI: 0.02, 0.26; P = 0.02) at 12 months. The
positive association of FIFs with subsequent growth may be attributed to their
content of both powdered cow's milk and multi-micronutrient fortificants.
Nonetheless, mothers should not be encouraged to over-rely on FIFs as they reduce
DD.
PMID- 28426829
TI - Joint genetic analysis using variant sets reveals polygenic gene-context
interactions.
AB - Joint genetic models for multiple traits have helped to enhance association
analyses. Most existing multi-trait models have been designed to increase power
for detecting associations, whereas the analysis of interactions has received
considerably less attention. Here, we propose iSet, a method based on linear
mixed models to test for interactions between sets of variants and environmental
states or other contexts. Our model generalizes previous interaction tests and in
particular provides a test for local differences in the genetic architecture
between contexts. We first use simulations to validate iSet before applying the
model to the analysis of genotype-environment interactions in an eQTL study. Our
model retrieves a larger number of interactions than alternative methods and
reveals that up to 20% of cases show context-specific configurations of causal
variants. Finally, we apply iSet to test for sub-group specific genetic effects
in human lipid levels in a large human cohort, where we identify a gene-sex
interaction for C-reactive protein that is missed by alternative methods.
PMID- 28426830
TI - Correction: p16INK4a Expression and Immunologic Aging in Chronic HIV Infection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166759.].
PMID- 28426831
TI - Representation and reporting of kidney disease in cerebrovascular disease: A
systematic review of randomized controlled trials.
AB - Patients with kidney disease (KD) are at increased risk for cerebrovascular
disease (CVD) and CVD patients with KD have worse outcomes. We aimed to determine
the representation of KD patients in major randomized controlled trials (RCTs) of
CVD interventions. We searched MEDLINE for reports of major CVD trials published
through February 9, 2017. We excluded trials that did not report mortality
outcomes, enrolled fewer than 100 participants, or were subgroup, follow-up, or
post-hoc analyses. Two independent reviewers performed study selection and data
extraction. We included 135 RCTs randomizing 194,977 participants. KD patients
were excluded in 48 (35.6%) trials, but were less likely to be excluded from
trials of class I/II recommended interventions (n = 7; 15.9%; p = 0.001) and more
likely to be excluded in trials with registered protocols (45.5% vs. 22.4%; p =
0.007). Exclusion was lower in trials supported by academic or governmental
grants compared to industry or combined funding (21.2% vs. 42.0% and 47.8%; p =
0.033 and 0.028, respectively). Among trials excluding KD patients, 24 (50.0%)
used serum creatinine, 7 (14.6%) used estimated glomerular filtration rate or
creatinine clearance, 7 (14.6%) used renal replacement therapy, and 19 (39.6%)
used non-specific kidney-related criteria. Only 4 (3.0%) trials reported baseline
renal function. No trials prespecified or reported subgroup analyses by baseline
renal function. Although 19 (14.1%) trials reported the incidence of acute kidney
injury, no trial examined adverse event rates according to renal function. In
summary, more than one third of major CVD trials excluded patients with KD,
primarily based on serum creatinine or non-specific criteria, and outcomes were
not stratified by renal parameters. Therefore, purposeful efforts to increase
inclusion of KD patients in CVD trials and evaluate the impact of renal function
on efficacy and safety are needed to improve the quality of evidence for
interventions in this vulnerable population.
PMID- 28426833
TI - Correction: Modulation of behaviour and virulence of a high alginate expressing
Pseudomonas aeruginosa strain from cystic fibrosis by oral commensal bacterium
Streptococcus anginosus.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173741.].
PMID- 28426832
TI - A systematic review of pragmatic language interventions for children with autism
spectrum disorder.
AB - There is a need for evidence based interventions for children with autism
spectrum disorder (ASD) to limit the life-long, psychosocial impact of pragmatic
language impairments. This systematic review identified 22 studies reporting on
20 pragmatic language interventions for children with ASD aged 0-18 years. The
characteristics of each study, components of the interventions, and the
methodological quality of each study were reviewed. Meta-analysis was conducted
to assess the effectiveness of 15 interventions. Results revealed some promising
approaches, indicating that active inclusion of the child and parent in the
intervention was a significant mediator of intervention effect. Participant age,
therapy setting or modality were not significant mediators between the
interventions and measures of pragmatic language. The long-term effects of these
interventions and the generalisation of learning to new contexts is largely
unknown. Implications for clinical practice and directions for future research
are discussed.
PMID- 28426834
TI - Acceptability of an open-label wait-listed trial design: Experiences from the
PROUD PrEP study.
AB - BACKGROUND: PROUD participants were randomly assigned to receive pre-exposure
prophylaxis (PrEP) immediately or after a deferred period of one-year. We report
on the acceptability of this open-label wait-listed trial design. METHODS:
Participants completed an acceptability questionnaire, which included categorical
study acceptability data and free-text data on most and least liked aspects of
the study. We also conducted in-depth interviews (IDI) with a purposely selected
sub-sample of participants. RESULTS: Acceptability questionnaires were completed
by 76% (415/544) of participants. After controlling for age, immediate-group
participants were almost twice as likely as deferred-group participants to
complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the
majority of participants in both groups found the wait-listed design acceptable
when measured by satisfaction of joining the study, intention to remain in the
study, and interest in joining a subsequent study. However, three-quarters
thought that the chance of being in the deferred-group might put other volunteers
off joining the study. In free-text responses, data collection tools were the
most frequently reported least liked aspect of the study. A fifth of deferred
participants reported 'being deferred' as the thing they least liked about the
study. However, more deferred participants disliked the data collection tools
than the fact that they had to wait a year to access PrEP. Participants in the
IDIs had a good understanding of the rationale for the open-label wait-listed
study design. Most accepted the design but acknowledged they were, or would have
been, disappointed to be randomised to the deferred group. Five of the 25
participants interviewed reported some objection to the wait-listed design.
CONCLUSION: The quantitative and qualitative findings suggest that in an
environment where PrEP was not available, the rationale for the wait-listed trial
design was well understood and generally acceptable to most participants in this
study.
PMID- 28426835
TI - Outcomes from a cohort of patients with acute kidney injury subjected to
continuous venovenous hemodiafiltration: The role of negative fluid balance.
AB - BACKGROUND: Several factors influence the outcomes in acute kidney injury (AKI),
especially in intensive care unit (ICU) patients. In this scenario, continuous
renal replacement therapies (CRRT) are used to control metabolic derangements and
blood volume. Knowing this fact, it may be possible to change the course of the
disease and decrease the high mortality rate observed. Thus, we aimed to evaluate
the main risk factors for death in AKI patients needing CRRT. RESULTS: This was a
prospective, observational cohort study of ICU patients (N = 183) with AKI who
underwent continuous venovenous hemodiafiltration (CVVHDF) as their initial
dialysis modality choice. The patients were predominantly male (62.8%) and their
median age was 65 (55-76) years. The most frequent comorbidities were
cardiovascular disease (39.3%), hypertension (32.8%), diabetes (24%), and
cirrhosis (20.7%). The main cause of AKI was sepsis (52.5%). At beginning of
CVVHDF, 152 patients (83%) were using vasopressors. The median SAPS 3 and SOFA
score at ICU admission was 61 (50-74) and 10 (7-12), respectively. The dialysis
dose delivered was 33.2 (28.9-38.7) ml/kg/h. The median time between ICU
admission and CVVHDF initiation was 2 (1-4) days. The median cumulative fluid
balance during the CVVHDF period was -1838 (-5735 +2993) ml. The mortality rate
up to90 days was 58%. The independent mortality risk factors in propensity score
model were: chronic obstructive pulmonary disease (OR = 3.44[1.14-10.4; p =
0.028]), hematologic malignancy (OR = 5.14[1.66-15.95; p = 0.005]), oliguria (OR
= 2.36[1.15-4.9; p = 0.02]), positive daily fluid balance during CVVHDF (OR =
4.55[2.75-13.1; p<0.001]), and total SOFA score on first dialysis day (OR =
1.27[1.12-1.45; p<0.001]). CONCLUSIONS: Dialysis-related factors may influence
the outcomes. In our cohort, positive daily fluid balance during CRRT was
associated with lower survival. Multicenter, randomized studies are needed to
assess fluid balance as a primary outcome to define the best strategy in this
patient population.
PMID- 28426836
TI - Facework and trust in facilitating health-focused housing interventions.
AB - The link between housing and health is of increasing importance in the UK policy
and practice context, in which poor housing is often accepted as a social
determinant of poor health. Service users' experiences of, and outcomes from, a
British information, advice, support and guidance service focused on the
relationship between housing problems and health issues were explored. This
service facilitates home improvements for privately housed residents with housing
issues exacerbating or causing health problems. In-depth interviews with
occupants of 15 households which received the service were completed. The
findings highlighted three key themes: the need for participants' person-home fit
to reflect and adapt to any degeneration in health conditions; the facilitation
of knowledge and access to housing and other support available to them; and
perceived positive health and wellbeing outcomes from the receipt of personalised
advice and support. The delivery of these outcomes by a named officer of the
service team, and the relationship this developed with the service user, are
considered within the context of facework, whereby they became a trusted source
of guidance in navigating a complex system of assistance. These findings add to
the growing knowledge base on housing and health, and also highlight the critical
importance of a facework approach in allowing service users to navigate complex
systems in order to achieve beneficial outcomes.
PMID- 28426837
TI - The high prevalence of HPV and HPV16 European variants in cervical and anal
samples of HIV-seropositive women with normal Pap test results.
AB - Human Immunodeficiency Virus (HIV)-seropositive women are more likely to have
anogenital cancer, and high risk-HPV (HR-HPV) infection is the main associated
factor. Between August 2013 and December 2015, we conducted a descriptive study
to determine the HPV genotypes and HPV16 variants in cervical and anal samples of
HIV-seropositive women with a normal Pap test. The viral DNA was amplified by PCR
using the PGMY09/11 set of primers. Reverse line blot (RLB), restriction fragment
length polymorphism (RFLP) and sequencing assays were used to determine the HPV
genotypes. HPV16 variants were identified by gene sequencing. We found a high
frequency of HR-HPV (60.3%; 76/126) at the anogenital site among HIV-seropositive
women and without association with anal intercourse. HPV16 and European variant
predominated among the HR-HPV. Mixed infections with at least three different HPV
types were common, particularly at the anal site. CD4+ T-cell counts below 500
cells/mm3, a HIV viral load above 50 copies/mL and an age of 18 to 35 years old
were all related to HPV anal infection. Our study showed a high frequency of HR
HPV in both cervical and anal sites of women with negative cytology belonging to
a risk group for the development of anogenital cancer.
PMID- 28426839
TI - Medical History in the Hellenic Journal of Nuclear Medicine.
AB - The Hellenic Journal of Nuclear Medicine is about to celebrate its 20th
anniversary end of 2017. On board of the editorial team since 2003, this journal
has influenced me like a good friend over the many past years. From time to time,
the journal has published interesting and valuable historical notes. They show
that nuclear medicine has a history and that medicine is its basis. They also
teach us today, and some of the ancient perspectives and approaches are still
valid. The reader of HJNM may be interested in these historical contributions, as
they are timeless. Therefore, it was our idea to summarize these in the following
pages. Where there is a link to the free article, this is noted. Upon opening all
articles, you will find out that these are a book or so of its own. In thanks to
the editor-in-chief of the Journal for his continuing support on the historical
section. Below we refer to the historical papers of the Journal: History of
Nuclear Medicine. Nuclear Medicine and History of Science and Philosophy: Atomic
Theory of the Matter. G.N. Sfakianakis, 2001; 4(3); 155-60. Editorial. Pioneers
of nuclear medicine, Madame Curie. P.C. Grammaticos. 2004; 7(1); 29-30.
http://nuclmed.web.auth.gr/ magazine/eng/jan04/editorial.htm Editor's note.
Hippocrates' Oath. The editor. 2004; 7(1); 31. Editorial. Useful known and
unknown views of the father of modern medicine, Hippocrates and his teacher
Democritus. P. Grammaticos, A. Diamantis. 2008; 11(1): 2-4.
http://nuclmed.web.auth.gr/magazine/eng/jan08/2.pdf Special Article. The
contribution of Maria Sklodowska-Curie and Pierre Curie to Nuclear and Medical
Physics. A hundred and ten years after the discovery of radium. A. Diamantis, E.
Magiorkinis, 2008; 11(1): 33-8. http://nuclmed.web.auth.gr/magazine/
eng/jan08/33.pdf Brief Historical Review. Lymphatic system and
lymphoscintigraphy. P. Valsamaki. 2009; 12(1): 87-89. http://nuclmed.web.
auth.gr/magazine/eng/jan09/89.pdf (In Greek) Historical Review. The philosophic
and biological views of the "atomic" philosophers, Leucippus and Democritus. E.
Magiorkinis. A. Beloukas, A. Diamantis. 2010; 13(2): 111-117.
http://nuclmed.web.auth.gr/magazine/eng/may10/9.pdf Correspondence. Neuroimaging
in mild traumatic brain injury and M. Ravel's injury. A. Otte. 2012; 15(1): 76.
http://nuclmed. web.auth.gr/magazine/eng/jan12/3.pdf Selected Brief
Contributions. The "atomic theory" of Leucippus, and its impact on medicine
before Hippocrates. G. Tsoucalas, K. Laios et al. 2013; 16(1): 68-9.
http://nuclmed.web.auth.gr/magazine/eng/jan13/72.pdf Selected Brief
Contributions. Computed tomography alone reveals the secrets of ancient mummies
in medical archaeology. A. Otte, T. Thieme et al. 2013; 16(2): 148-9.
http://nuclmed.web.auth.gr/magazine/eng/may13/70.pdf Editorial. The timeless
influence of Hippocratic ideas on diet, salicylates and personalized medicine.
T.C. Karagiannis. 2014; 17(1): 2-6.
http://nuclmed.web.auth.gr/magazine/eng/jan14/1.pdf Historical Article. The
physician who first applied radiotherapy, Victor Despeignes, on 1896. M.
Sgantzos, G. Tsoucalas et al. 2014; 17(1): 45-6.
http://nuclmed.web.auth.gr/magazine/eng/jan14/11.pdf Original Articles. Medical
practice applied in the ancient Asclepeion in Kos island. M. Mironidou
Tzouveleki, P.M. Tzitzis. 2014; 17(3): 167-70.
http://www.nuclmed.web.auth.gr/magazine/eng/sept14/3.pdf Special Historical
Article. How a tertiary medical nuclear medicine department at the Himalayan area
in India can be established and function in an exemplary manner. Basic rules
revisited. V.K. Dhingra, S. Saini et al. 2015; 18(3): 252-6. http://
nuclmed.web.auth.gr/magazine/eng/sept15/13.pdf Historical and Commentary Note.
Johann Sebastian Bach's "Goldberg variations" to treat insomnia from renal
lithiasis pain. Sleep research in Nuclear Medicine. A. Otte. 2016; 19(1): 13-4.
http://nuclmed.web.auth.gr/magazine/eng/jan16/06.pdf Historical Review. The first
medical ethics and deontology in Europe as derived from Greek mythology. M.K.
Konstantinidou. 2016; 19(2): 155
8.http://nuclmed.web.auth.gr/magazine/eng/may16/11.pdf Historical-Technical
Article. The beginning of using X-rays and the evolution of equipment for the
treatment of ocular cancer. K. Laios, M. Zozoglou. 2017; 20(1): Ahead of print.
And hopefully many more to follow!
PMID- 28426838
TI - A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected
epithelial cells.
AB - Type III secretion system 1 (T3SS1) is used by the enteropathogen Salmonella
enterica serovar Typhimurium to establish infection in the gut. Effector proteins
translocated by this system across the plasma membrane facilitate invasion of
intestinal epithelial cells. One such effector, the inositol phosphatase SopB,
contributes to invasion and mediates activation of the pro-survival kinase Akt.
Following internalization, some bacteria escape from the Salmonella-containing
vacuole into the cytosol and there is evidence suggesting that T3SS1 is expressed
in this subpopulation. Here, we investigated the post-invasion role of T3SS1,
using SopB as a model effector. In cultured epithelial cells, SopB-dependent Akt
phosphorylation was observed at two distinct stages of infection: during and
immediately after invasion, and later during peak cytosolic replication. Single
cell analysis revealed that cytosolic Salmonella deliver SopB via T3SS1. Although
intracellular replication was unaffected in a SopB deletion mutant, cells
infected with DeltasopB demonstrated a lack of Akt phosphorylation, earlier time
to death, and increased lysis. When SopB expression was induced specifically in
cytosolic Salmonella, these effects were restored to levels observed in WT
infected cells, indicating that the second wave of SopB protects this infected
population against cell death via Akt activation. Thus, T3SS1 has two, temporally
distinct roles during epithelial cell colonization. Additionally, we found that
delivery of SopB by cytosolic bacteria was translocon-independent, in contrast to
canonical effector translocation across eukaryotic membranes, which requires
formation of a translocon pore. This mechanism was also observed for another
T3SS1 effector, SipA. These findings reveal the functional and mechanistic
adaptability of a T3SS that can be harnessed in different microenvironments.
PMID- 28426840
TI - Multimodality-multiparametric brain tumors evaluation.
AB - Brain tumors represent a vast group of lesions, originating from different
neuronal cells with different degrees of aggressiveness. Despite some
technological advances either pre or post-treatment, these tumors may share
similar imaging findings and properties, rendering diagnosis/prognosis, an
ambiguous process. Gadolinium-enhanced magnetic resonance imaging remains the
gold standard for providing detailed morphologic information, but presents
several limitations due to the overlap of findings, in cases such as progressive
tumor and post-radiation related effects. Tumor cellularity, vascularity,
proliferative activity, metabolic and functional profiles are a few of many
characteristics that may further support tumor classification, but cannot be
assessed by conventional imaging alone. We review the aforementioned factors and
indicate how they improve tumor characterization and grading in order to design
the optimal treatment strategy and better evaluate post treatment efficacy.
PMID- 28426841
TI - Bilateral Retinal Whitening in a Hospitalized Patient.
PMID- 28426842
TI - Association of Patient Age With Outcomes of Current-Era, Large-Scale Screening
Mammography: Analysis of Data From the National Mammography Database.
PMID- 28426843
TI - Understanding the Risks and Harms of Management of Incidental Thyroid Nodules: A
Review.
AB - Importance: Incidental thyroid nodules are defined as nodules originally detected
in a patient with no thyroid-related clinical symptoms, examination findings, or
suspected thyroid disease. Medical imaging for diseases in the neck, chest, and
spine is a common source of incidental thyroid nodules. They are easily detected
but poorly characterized. The next step is to decide whether the incidental
thyroid nodule should be further evaluated with ultrasonography. Observations:
Indiscriminate workup of incidental thyroid nodules with ultrasonography is not
cost-effective and is potentially harmful. Although the concern for malignant
neoplasms drives workup, the risk for poor outcomes without evaluation is
minimal. The rate of malignant tumors in patients with 1 or more thyroid nodules
larger than 5 mm is only 1.6%, and most small thyroid cancers are indolent.
Substantial evidence suggests that a reservoir of thyroid cancers does not
progress, and workup after detection with imaging leads to epidemiologic
overdiagnosis. Finally, a significant proportion of patients with benign nodules
have cytologic results that are not definitive and require lobectomy. Evidence
based recommendations for incidental thyroid nodules detected at computed
tomography, magnetic resonance imaging, nuclear medicine studies, and
extrathyroidal ultrasonography include selection criteria for nodule workup based
on suspicious imaging findings, patient age, and nodule size. In the absence of
clinical risk factors or suspicious imaging findings, workup with dedicated
thyroid ultrasonography is only recommended for nodules at least 1.5 cm in
patients 35 years or older and for nodules at least 1.0 cm in patients younger
than 35 years. Conclusions and Relevance: Only a few select incidental thyroid
nodules require further evaluation with ultrasonography based on recommendations
that aim to diagnose clinically significant thyroid cancers while reducing
unnecessary workup and provide guidance for clinical practice.
PMID- 28426844
TI - Beyond Medication Reconciliation: The Correct Medication List.
PMID- 28426846
TI - Affordability of Cancer Drugs in Sub-Saharan Africa: Effects of Pricing on
Needless Loss of Life.
PMID- 28426845
TI - HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for
Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.
AB - Importance: Glioblastoma is an incurable tumor, and the therapeutic options for
patients are limited. Objective: To determine whether the systemic administration
of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells
(VSTs) is safe and whether these cells have antiglioblastoma activity. Design,
Setting, and Participants: In this open-label phase 1 dose-escalation study
conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas
Children's Hospital, patients with progressive HER2-positive glioblastoma were
enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was
10 weeks to 29 months (median, 8 months). Interventions: Monotherapy with
autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus
and genetically modified to express HER2-CARs with a CD28.zeta-signaling
endodomain (HER2-CAR VSTs). Main Outcomes and Measures: Primary end points were
feasibility and safety. The key secondary end points were T-cell persistence and
their antiglioblastoma activity. Results: A total of 17 patients (8 females and 9
males; 10 patients >=18 years [median age, 60 years; range, 30-69 years] and 7
patients <18 years [median age, 14 years; range, 10-17 years]) with progressive
HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR
VSTs (1 * 106/m2 to 1 * 108/m2) without prior lymphodepletion. Infusions were
well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected
in the peripheral blood for up to 12 months after the infusion by quantitative
real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7
children), 1 had a partial response for more than 9 months, 7 had stable disease
for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients
with stable disease are alive without any evidence of progression during 24 to 29
months of follow-up. For the entire study cohort, median overall survival was
11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5
months (95% CI, 17.2-34.6 months) from diagnosis. Conclusions and Relevance:
Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical
benefit for patients with progressive glioblastoma. Further evaluation of HER2
CAR VSTs in a phase 2b study is warranted as a single agent or in combination
with other immunomodulatory approaches for glioblastoma.
PMID- 28426847
TI - Safety and Efficacy of Bilateral Submental Cryolipolysis With Quantified 3
Dimensional Imaging of Fat Reduction and Skin Tightening.
AB - Importance: Cryolipolysis is a popular, well-tolerated nonsurgical procedure that
uses controlled cooling to selectively destroy fat cells. Central submental
cryolipolysis has been reported to be safe and effective, but many patients would
benefit from extending this treatment over the entire submental region.
Objective: To investigate the safety and efficacy of cryolipolysis for reduction
of lateral and central submental fat. Design, Setting, and Participants: The
study population consisted of 14 participants who were treated from January 22 to
June 30, 2016, in the lateral and central submental area to reduce unwanted
subcutaneous fat. A small-volume cup applicator was used to administer 2
cryolipolysis treatments, delivered in 45-minute treatment cycles in 2 sessions.
For the first treatment session, all participants received bilateral treatments
with approximately 20% overlap of the treatment area. At the 6-week follow-up
visit, participants were reassessed to determine whether they would benefit from
a second treatment and to determine the number of cycles needed to achieve the
optimal aesthetic result, and then they were treated a second time. Main Outcomes
and Measures: Participant surveys assessed tolerability and treatment
satisfaction at 12 weeks following the second treatment. Clinicians monitored
adverse events to assess safety. Caliper measurements were recorded to assess fat
thickness reduction. Treatment efficacy was objectively evaluated using 2
dimensional and 3-dimensional imaging. Results: Among the 14 participants (12
women and 2 men; mean [SD] age, 50.5 [10.4] years), the adverse effects of the
procedure were typically mild and included numbness and tingling, which resolved
without intervention by the final 12-week follow-up visit. An independent review
of digital photographs revealed an 81.0% (95% CI, 65.9%-91.4%; P = .02) correct
identification rate (34 of 42 images) of the pretreatment and posttreatment
images. Caliper measurements demonstrated a mean (SD) fat layer reduction of 2.3
(0.8) mm (range, 0.7-3.5 mm). Three-dimensional imaging revealed a mean (SD)
reduction in fat volume of 4.82 (11.42) cm3 (from a reduction of 32.69 cm3 to an
increase of 13.85 cm3), in skin surface area of 1.29 (1.42) cm2 (from a reduction
of 3.18 cm2 to an increase of 0.99 cm2), and in fat thickness of 3.77 (3.59) mm
(from of reduction of 13.10 mm to an increase of 0.47 mm). Results of participant
surveys indicated that 13 participants (93%) were satisfied with the
cryolipolysis treatment. Conclusions and Relevance: Although safe and efficacious
central submental cryolipolysis has been reported, this is the first clinical
study of cryolipolysis for treatment of the entire submental area using
overlapping bilateral treatments and a shorter treatment duration. The study
demonstrates that bilateral submental cryolipolysis is well tolerated and
produces visible and significant fat layer reduction. Level of Evidence: 4.
PMID- 28426848
TI - Differences in Survival With Surgery and Postoperative Radiotherapy Compared With
Definitive Chemoradiotherapy for Oral Cavity Cancer: A National Cancer Database
Analysis.
AB - Importance: Because locally advanced oral cavity squamous cell carcinoma (OCSCC)
is often treated with surgery followed by postoperative radiotherapy (S+PORT),
the effectiveness of organ preservation with concurrent chemoradiotherapy (CRT)
remains unclear. Objective: To compare the differences in survival between
patients with locally advanced OCSCC treated with S+PORT or CRT. Design, Setting,
and Participants: Using the National Cancer Database, this study compared 6900
patients with stage III to IVA OCSCC treated with S+PORT and CRT from 2004
through 2012 at academic and community-based cancer clinics. Comparisons were
made using Kaplan-Meier methods and Cox proportional hazards regression models
using the entire cohort and a propensity score-matched cohort of 2286 patients.
Main Outcomes and Measures: Overall survival (OS). Results: Of the 6900 study
patients, 4809 received S+PORT (3080 male [64.0%] and 1792 [36.0%] female) and
2091 received CRT (1453 male [69.5%] and 638 [30.5%] female). Median follow-up
for the entire group was 23.0 months overall but was shorter for patients
receiving CRT (17.3-month) vs S+PORT (25.6 months). Patients receiving CRT were
more likely to be older than 60 years, treated before 2007, live within 10 miles
of the treating facility, treated at nonacademic centers, have more
comorbidities, have T3 to T4a tumors, and have N2a to N2c nodal disease.
Propensity score matching identified cohorts of patients with similar clinical
variables. S+PORT was associated with improved survival among all patients (3
year OS: 53.9% for S+PORT vs 37.8% for CRT; difference = 16.1%; 95% CI, 13.6%
18.6%) and in the propensity score-matched cohort (3-year OS: 51.8% for S+PORT vs
39.3% for CRT; difference = 11.9%; 95% CI, 7.8%-16.0%). S+PORT was associated
with improved survival among patients with T3 to T4a tumors (3-year OS: 49.7% for
S+PORT vs 36.0% for CRT; difference = 16.1%; 95% CI, 13.6%-18.6%) but was not
associated with improved survival among patients with T1 to T2 tumors (3-year OS:
59.1% for S+PORT vs 53.5% for CRT; difference = 5.6%; 95% CI, -3.1% to 14.3%).
Conclusions and Relevance: Compared with CRT, S+PORT was associated with improved
survival for locally advanced OCSCCs, especially in T3 to T4a disease. These data
support the use of surgery as the initial treatment modality for operable OCSCCs.
PMID- 28426849
TI - Effect of Adalimumab on Visual Functioning in Patients With Noninfectious
Intermediate Uveitis, Posterior Uveitis, and Panuveitis in the VISUAL-1 and
VISUAL-2 Trials.
AB - Importance: Adalimumab was recently approved for the treatment of noninfectious
intermediate uveitis, posterior uveitis, and panuveitis. Objective: To assess the
effect of adalimumab on the visual functioning and quality of life in patients
with corticosteroid-dependent noninfectious intermediate uveitis, posterior
uveitis, and panuveitis. Design: A post hoc analysis of clinical trials of adults
with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate
uveitis, posterior uveitis, and panuveitis was conducted in the United States,
Canada, Europe, Israel, Australia, Latin America, and Japan. A total of 217
patients (110 adalimumab, 107 placebo) in VISUAL-1 and 226 patients (115
adalimumab, 111 placebo) in VISUAL-2 were studied using intent-to-treat analyses.
The clinical trials were conducted between August 10, 2010, and May 14, 2015.
Interventions: In VISUAL-1 and VISUAL-2, patients were randomized to receive
adalimumab, 80-mg, subcutaneous loading dose followed by 40 mg every other week
or placebo for 80 weeks. All patients underwent prednisone tapering, with
patients in VISUAL-1 receiving an initial prednisone burst. Main Outcomes and
Measures: The 25-item National Eye Institute Vision Function Questionnaire (NEI
VFQ-25) composite score questionnaire assessed the impact of visual impairment
from the patient's perspective; scores on the questionnaire range from 0 to 100,
with higher scores indicating better vision-related quality of life. The change
in NEI VFQ-25 from best state achieved prior to week 6 (VISUAL-1) and from
baseline state (VISUAL-2) to the final or early termination visit was determined
in each group and statistically compared using analysis of variance. The temporal
effects of adalimumab and placebo on NEI VFQ-25 were investigated using a
longitudinal model. Results: Of the 217 patients in VISUAL-1, 124 (57.1%) were
women; the mean (SD) age was 42.7 (14.9) years. Of the 226 patients in VISUAL-2,
138 (61.1%) were women; the mean (SD) age was 42.5 (13.4). In VISUAL-1, the
change from final score to best score in NEI VFQ-25 was -1.30 for adalimumab and
5.50 for placebo-a difference of 4.20 (95% CI, 1.04 to 7.36; P = .01) associated
with adalimumab compared with placebo. In VISUAL-2, the change from baseline NEI
VFQ-25 was 3.36 for adalimumab and 1.24 for placebo-a difference of 2.12 (95% CI,
-0.81 to 5.04; P = .16). In both trials, the longitudinal models showed a
significant difference in NEI VFQ-25 between adalimumab and placebo of 3.07 (95%
CI, 2.09 to 4.06; P < .001) and 4.66 (95% CI, 0.05 to 9.26; P = .048) in the
VISUAL-1 (74.15 vs 71.08) and VISUAL-2 (82.39 vs 77.73) trials, respectively.
Conclusions and Relevance: This post hoc analysis suggests that adalimumab is
associated with statistically significant and clinically meaningful improvements
in patient-reported visual functioning for patients with noninfectious
intermediate uveitis, posterior uveitis, and panuveitis. Trial Registration:
clinicaltrials.gov Identifiers: NCT01138657 (VISUAL-1) and NCT01124838 (VISUAL
2).
PMID- 28426850
TI - Second Primary Malignant Neoplasms and Survival in Adolescent and Young Adult
Cancer Survivors.
AB - Importance: Although the increased incidence of second primary malignant
neoplasms (SPMs) is a well-known late effect after cancer, few studies have
compared survival after an SPM to survival of the same cancer occurring as first
primary malignant neoplasm (PM) by age. Objective: To assess the survival impact
of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that
of pediatric (<15 years) and older adult (>=40 years) patients with the same
SPMs. Design, Setting, and Participants: This was a population-based,
retrospective cohort study of patients with cancer in 13 Surveillance,
Epidemiology and End Results regions in the United States diagnosed from 1992 to
2008 and followed through 2013. Data analysis was performed between June 2016 and
January 2017. Main Outcomes and Measures: Five-year relative survival was
calculated overall and for each cancer occurring as a PM or SPM by age at
diagnosis. The impact of SPM status on cancer-specific death was examined using
multivariable Cox proportional hazards regression. Results: A total of 15 954
pediatric, 125 750 AYAs, and 878 370 older adult patients diagnosed as having 14
cancers occurring as a PM or SPM were included. Overall, 5-year survival after an
SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older
adults compared with a PM at the same age. For the most common SPMs in AYAs, the
absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin
lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid
carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was
significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma,
non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central
nervous system cancer. Adolescents and young adults with secondary Hodgkin
lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1
3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]);
and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival
compared with AYAs with the same PMs. Conclusion and Relevance: The adverse
impact of SPMs on survival is substantial for AYAs and may partially explain the
relative lack of survival improvement in AYAs compared with other age groups. The
impact of a particular SPM diagnosis on survival may inform age-specific
prevention, screening, treatment, and survivorship recommendations.
PMID- 28426851
TI - Unilateral Hearing Loss and Otorrhea.
PMID- 28426853
TI - A Cautious but Optimistic Opinion of Submental Cryolipolysis.
PMID- 28426852
TI - An Outbreak of Endogenous Fungal Endophthalmitis Among Intravenous Drug Abusers
in New England.
AB - Importance: Intravenous drug abuse (IVDA) is a known risk factor for endogenous
fungal endophthalmitis (EFE), a severe intraocular infection caused by
hematogenous seeding of mycotic organisms to the eye. Reporting significant
increases in heroin-related deaths since 2014, the New England region is in the
midst of an opioid crisis that has led to a substantial increase in patients at
risk for this vision-threatening disease. Objective: To present an update on
characteristics, management, and visual outcomes in patients with EFE. Design,
Setting, and Participants: Medical records review was initiated on July 1, 2016,
evaluating all patients with EFE referred to New England Eye Center at Tufts
Medical Center, a tertiary care ophthalmology practice distributed throughout
Massachusetts, from May 1, 2014, to May 1, 2016. Patients with a history of IVDA
and culture-proven or clinical evidence of fungal endophthalmitis were included.
Exposures: Intravenous drug use. Main Outcomes and Measures: Patient
demographics, comorbidities, presenting symptoms and vision, vitreoretinal
findings, treatment regimens, culture data, and final visual acuities. Results:
Ten patients (5 women) with IVDA-related EFE were identified between May 1, 2014,
and May 1, 2016-an increase from 3 patients treated from May 2012 to April 2014.
The mean (SD) patient age was 34 (11) years (range, 24-60 years). Presenting
visual acuities ranged from 20/25 to hand motion. The most common presenting
symptoms were floaters (n = 8), reduced vision (n = 6), and pain (n = 5). Initial
treatment included systemic antifungals in all patients and intravitreal
antifungals in 9 eyes. Five patients required pars plana vitrectomy for worsening
vitritis. The most commonly isolated pathogen was Candida albicans in 20% of the
patients. Final visual acuity ranged from 20/40 to 20/300. Conclusions and
Relevance: The data provided in this report suggest that EFE represents severe
end organ damage associated with IVDA and portends poor visual outcomes. Health
care professionals must maintain a high suspicion for EFE, as patients are
typically ambulatory on presentation without systemic signs of infection.
PMID- 28426854
TI - Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal
Subarachnoid Hemorrhage: Data From the Simvastatin in Aneurysmal Subarachnoid
Hemorrhage (STASH) Trial: Erratum.
PMID- 28426855
TI - Journal Club: Outpatient Cervical and Lumbar Spine Surgery is Feasible and Safe:
A Consecutive Single Center Series of 1449 Patients: Erratum.
PMID- 28426856
TI - Adjunctive Oral Voriconazole Treatment of Fusarium Keratitis: A Secondary
Analysis From the Mycotic Ulcer Treatment Trial II.
AB - Importance: Fusarium keratitis is common and often results in poor outcomes. No
new treatments since natamycin have become available. Objective: To explore the
role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis.
Design, Setting, and Participants: In this prespecified subgroup analysis of a
multicenter, double-masked, placebo-controlled randomized clinical trial, 240
patients from the Aravind Eye Care System in India, the Lumbini Eye Hospital and
Bharatpur Eye Hospital in Nepal, and the University of California, San Francisco,
who had culture-positive fungal ulcer and baseline visual acuity of 20/400 or
worse were randomized to receive oral voriconazole vs placebo. Enrollment started
May 24, 2010, and the last patient study visit was November 23, 2015. All
patients received topical voriconazole, 1%, and after the results of the Mycotic
Ulcer Treatment Trial (MUTT) II became available, topical natamycin, 5%, was
added for all patients. Data analysis was performed from September 2 to October
28, 2016. Main Outcomes and Measures: The primary outcome of the trial was the
rate of corneal perforation or the need for therapeutic penetrating keratoplasty.
Secondary outcomes included rate of reepithelialization, best spectacle-corrected
visual acuity, and infiltrate or scar size at 3 months. Results: Of the 240 study
participants, 72 (30.4%) were culture positive for Fusarium species (41 [56.9%]
male and 31 [43.1%] female; median [interquartile range] age, 50 [45-57] years).
Of these, 33 (45.8%) were randomized to oral voriconazole and 39 (54.2%) to
placebo. Fusarium ulcers randomized to oral voriconazole had a 0.43-fold
decreased hazard of perforation or therapeutic penetrating keratoplasty compared
with placebo after controlling for baseline infiltrate depth (95% CI, 0.22-fold
to 0.84-fold; P = .01). Multiple linear regression revealed a 1.89-mm decreased
infiltrate and/or scar size at 3 weeks (95% CI, -2.69 to -1.09 mm; P < .001) and
a 0.83-mm decreased infiltrate and/or scar size at 3 months after correcting for
baseline values (95% CI, -1.33 to -0.32 mm; P = .001) in eyes randomized to oral
voriconazole vs placebo. Eyes treated with oral voriconazole also had a mean 0.29
decreased logMAR (improved) (Snellen equivalent 20/40) visual acuity at 3 months
after controlling for baseline visual acuity, although this finding was not
statistically significant (95% CI, -0.57 to 0.002; P = .052). Conclusions and
Relevance: Although MUTT II could not find a benefit for all corneal ulcers,
Fusarium keratitis may benefit from the addition of oral voriconazole to topical
natamycin, and physicians should consider prescribing oral voriconazole in these
cases. Trial Registration: clinicaltrials.gov Identifier: NCT00996736.
PMID- 28426857
TI - Spectacle Wear Among Children in a School-Based Program for Ready-Made vs Custom
Made Spectacles in India: A Randomized Clinical Trial.
AB - Importance: Uncorrected refractive errors are the most common cause of visual
impairment in children despite correction being highly cost-effective. Objective:
To determine whether less expensive ready-made spectacles produce rates of
spectacle wear at 3 to 4 months comparable to those of more expensive custom-made
spectacles among eligible school-aged children. Design, Setting, and
Participants: This noninferiority, double-masked, randomized clinical trial
recruited children aged 11 to 15 years from January 12 through July 31, 2015,
from government schools in urban and periurban areas surrounding Bangalore,
India. Follow-up occurred from August 1 through September 31, 2015. Participants
met the following eligibility criteria for ready-made spectacles: failed vision
screening at the 6/9 level in each eye; refraction was indicated; acuity improved
with correction by 2 or more lines in the better-seeing eye; the corrected acuity
with the spherical equivalent was not more than 1 line less than with full
correction; anisometropia measured less than 1.0 diopter; and an appropriate
frame was available. Interventions: Eligible children were randomized to ready
made or custom-made spectacles. Main Outcomes and Measures: Proportion of
children wearing their spectacles at unannounced visits 3 to 4 months after the
intervention. Results: Of 23 345 children aged 11 to 15 years who underwent
screening, 694 had visual acuity of less than 6/9 in both eyes, and 535 underwent
assessment for eligibility. A total of 460 children (227 female [49.3%] and 233
male [50.7%]; mean [SD] age, 13.4 [1.3] years) were eligible for ready-made
spectacles (2.0% undergoing screening and 86.0% undergoing assessment) and were
randomized to ready-made (n = 232) or custom-made (n = 228) spectacles. Follow-up
rates at 3 to 4 months were similar (184 [79.3%] in the ready-made group and 178
[78.1%] in the custom-made group). Rates of spectacle wear in the 2 arms were
similar among 139 of 184 children (75.5%) in the ready-made arm and 131 of 178
children (73.6%) in the custom-made arm (risk difference, 1.8%; 95% CI, -7.1% to
10.8%). Conclusions and Relevance: Most children were eligible for ready-made
spectacles, and the proportion wearing ready-made spectacles was not inferior to
the proportion wearing custom-made spectacles at 3 to 4 months. These findings
suggest that ready-made spectacles could substantially reduce costs for school
based eye health programs in India without compromising spectacle wear, at least
in the short term. Trial Registration: isrctn.com Identifier: ISRCTN14715120.
PMID- 28426858
TI - Improving More Than Just Vision in Noninfectious Uveitis.
PMID- 28426861
TI - Additional Data for Figures.
PMID- 28426864
TI - A Novel 3-Dimensional Printable Bone Substitute.
PMID- 28426865
TI - Decompressive Craniectomy for Traumatic Intracranial Hypertension.
PMID- 28426866
TI - Cognitive Fountain of Youth.
PMID- 28426867
TI - Stem Cell Transplantation Helps Alleviate Spinal Cord Injury Sequelae in Mice.
PMID- 28426868
TI - How Do We Decide? Macaque Orbitofrontal Cortex Neurons Encode Available Options
Independently in Subjective Decisions.
PMID- 28426869
TI - Expression Profiling of Nonpolar Lipids in Meibum From Patients With Dry Eye: A
Pilot Study.
AB - Purpose: The purpose of this investigation was to characterize differentially
expressed lipids in meibum samples from patients with dry eye disease (DED) in
order to better understand the underlying pathologic mechanisms. Methods: Meibum
samples were collected from postmenopausal women with DED (PW-DED; n = 5) and a
control group of postmenopausal women without DED (n = 4). Lipid profiles were
analyzed by direct infusion full-scan electrospray ionization mass spectrometry
(ESI-MS). An initial analysis of 145 representative peaks from four classes of
lipids in PW-DED samples revealed that additional manual corrections for peak
overlap and isotopes only slightly affected the statistical analysis. Therefore,
analysis of uncorrected data, which can be applied to a greater number of peaks,
was used to compare more than 500 lipid peaks common to PW-DED and control
samples. Statistical analysis of peak intensities identified several lipid
species that differed significantly between the two groups. Data from contact
lens wearers with DED (CL-DED; n = 5) were also analyzed. Results: Many species
of the two types of diesters (DE) and very long chain wax esters (WE) were
decreased by ~20% in PW-DED, whereas levels of triacylglycerols were increased by
an average of 39% +/- 3% in meibum from PW-DED compared to that in the control
group. Approximately the same reduction (20%) of similar DE and WE was observed
for CL-DED. Conclusions: Statistical analysis of peak intensities from direct
infusion ESI-MS results identified differentially expressed lipids in meibum from
dry eye patients. Further studies are warranted to support these findings.
PMID- 28426870
TI - A New Viscous Cysteamine Eye Drops Treatment for Ophthalmic Cystinosis: An Open
Label Randomized Comparative Phase III Pivotal Study.
AB - Purpose: The purpose of this study was to evaluate the efficacy of new viscous
cysteamine hydrochloride (CH) eye drops (vCH 0.55%) compared with standard CH
0.10% drops treatment. Methods: This was an open-label, phase III, randomized,
two-arm multicenter trial conducted at two centers in France. Cystinosis patients
>=2 years old were randomized 1:1 to receive eye drops, four times per day for 90
days in both eyes. We compared the superiority in reducing corneal cystine
crystal density as assessed by in vivo confocal microscopy (IVCM). We also
evaluated photophobia, corneal cystine crystal scores (CCCSs), and cystine
crystal depth measured by optical coherence tomography. Safety objectives were to
assess adverse events (AEs), local adverse drug reactions, and ocular safety
parameters. Results: We included 15 patients with vCH 0.55% and 16 patients with
CH 0.10% drops for 90 days. The mean absolute change in IVCM total score at day
90 in the vCH 0.55% drops group (-4.6 +/- 3.1) was significantly greater than and
superior to the mean absolute change in the CH 0.10% drops group (-0.46 +/- 3.38;
P < 0.0001). Photophobia, CCCS, and corneal cystine crystal depth were
significantly more improved in the vCH 0.55% drops group than in the CH 0.10%
group. The most frequent local adverse drug reactions in both groups were
stinging, burning, redness, and blurred vision. Conclusions: vCH 0.55% was
effective in reducing corneal cystine crystal density and superior to treatment
with CH 0.10% drops, which offer advantages over hospital pharmacy formulations
and is a more preferable and convenient treatment option.
PMID- 28426871
TI - Macular Pigment Density and Quantitative Fundus Autofluorescence in Young Healthy
Subjects.
AB - Purpose: To measure macular pigment (MP) and find possible correlation between
heterochromatic flicker photometry (HFP) and quantitative autofluorescence (qAF)
in young healthy subjects. Methods: We enrolled 80 eyes of 40 young healthy
subjects. Macular pigment optical density (MPOD) was automatically calculated
with a macular pigment screener (MPS; MPODHFP). We calculated qAF comparing gray
levels (GL) of qAF images with GL of internal reference of a confocal scanning
laser ophthalmoscopy. A raster of concentric rings was used to automatically
calculate foveal qAF (qAFF) values (0 degrees -1.2 degrees ); inner ring (1.3
degrees -4.3 degrees ; qAF3); middle ring (4.5 degrees -7 degrees ; qAF6); and
outer ring (7.2 degrees -9.7 degrees ; qAF8). The test-retest coefficient of
repeatability was calculated with Bland-Altman method. The between-eyes
coefficient of agreement and correlation between the two techniques were
calculated. Finally, an estimation of MPOD from qAF was performed (MPOD-AF), to
find possible direct correlations with MPODHFP obtained with the MPS II. Results:
Paired data sets of repeated measurements were not statistically different for
MPS II (P = 0.66); log qAFF (P = 0.95); log qAF3 (P = 0.48); log qAF6 (P = 0.4);
and log qAF8 (P = 0.56). Stepwise regression analysis showed negative correlation
between MPS II and log qAFF values (R2 = 0.35) with Spearman coefficient (rho) of
-0.60 (P < 0.01) and log qAF3 (R2 = 0.18; rho = -0.38.; P < 0.01). No correlation
was found between MPS II and log qAF6 (rho = 0.01, P = 0.93), neither with log
qAF8 (rho = -0.05, P = 0.66). Conclusions: In young healthy subjects, a negative
correlation between qAF values and MPODHFP was found in the central degrees.
However, qAF and HFP do not seem to be interchangeable: they represent two
opposite ways of estimating MP.
PMID- 28426872
TI - Importance and Difficulties of Pursuing rTMS Research in Acute Stroke.
AB - Although much research has been done on repetitive transcranial magnetic
stimulation (rTMS) in chronic stroke, only sparse research has been done in acute
stroke despite the particularly rich potential for neuroplasticity in this stage.
We attempted a preliminary clinical trial in one active, high-quality inpatient
rehabilitation facility (IRF) in the -United States. But after enrolling only 4
patients in the grant period, the study was stopped because of low enrollment.
The purpose of this paper is to offer a perspective describing the important
physiologic rationale for including rTMS in the early phase of stroke, the
reasons for our poor patient enrollment in our attempted study, and
recommendations to help future studies succeed. We conclude that, if scientists
and clinicians hope to enhance stroke outcomes, more attention must be directed
to leveraging conventional rehabilitation with neuromodulation in the acute phase
of stroke when the capacity for neuroplasticity is optimal. Difficulties with
patient enrollment must be addressed by reassessing traditional inclusion and
exclusion criteria. Factors that shorten patients' length of stay in the IRF must
also be reassessed at all policy-making levels to make ethical decisions that
promote higher functional outcomes while retaining cost consciousness.
PMID- 28426873
TI - High-fat diet induced leptin and Wnt expression: RNA-sequencing and pathway
analysis of mouse colonic tissue and tumors.
AB - Obesity, an immense epidemic affecting approximately half a billion adults, has
doubled in prevalence in the last several decades. Epidemiological data support
that obesity, due to intake of a high-fat, western diet, increases the risk of
colon cancer; however, the mechanisms underlying this risk remain unclear. Here,
utilizing next generation RNA sequencing, we aimed to determine the high-fat diet
(HFD) mediated expression profile in mouse colon and the azoxymethane/dextran
sulfate sodium model of colon cancer. Mice on HFD had significantly higher
colonic inflammation, tumor burden, and a number of differentially expressed
transcripts compared to mice on regular diet (RD). We identified 721 transcripts
differentially expressed in mouse HFD colon that were in a shared pattern with
colonic tumors (RD and HFD). Importantly, in mouse colon, HFD stimulated an
expression signature strikingly similar to human colon cancer, especially those
with inflammatory microsatellite instability. Furthermore, pathway analysis of
these transcripts demonstrated their association with active inflammation and
colon cancer signaling, with leptin and Wnt as the top two transcripts elevated
in mouse HFD colon shared with tumors. Moreover, in mouse colon, HFD-stimulated
tumorigenic Wnt pathway activation was further validated by upregulation of beta
catenin transcriptional targets. Finally, in human colon cancer, upregulation of
leptin pathway members was shown with a large network of dysregulated transcripts
being linked with worse overall survival.
PMID- 28426874
TI - The association between breast cancer and S100P methylation in peripheral blood
by multicenter case-control studies.
AB - Breast cancer (BC) is the leading cancer in women worldwide. Changes in DNA
methylation in peripheral blood could be associated with malignant diseases.
Making use of screening results by llumina 27K Methylation Assay, we validated
demethylation of five CpG sites of S100P gene in blood cell DNA of BC patients by
three independent retrospective studies with subjects from different centers
(Validation I: 235 familial BC case and 206 controls, odds ratio per -1%
methylation > 1.03, and P < 6.00 * 10-8 for all five CpG sites; Validation II:
189 sporadic BC case and 189 controls, odds ratio per -1% methylation > 1.03, P <
8.0 * 10-5 for four CpG sites; Validation III: 156 sporadic BC case and 151
controls, odds ratio per -1% methylation > 1.03, P < 6.0 * 10-4 for four CpG
sites). In addition, the blood-based S100P methylation pattern was similar among
BC patients with differential clinical characteristics regardless of stage,
receptor status and menopause status. The observed BC-associated decreased S100P
methylation in blood mainly originates from the leucocytes subpopulations but not
B cells. The methylation levels of most S100P CpG sites were inversely correlated
with the expression of S100P in leucocytes (P < 1.2 * 10-4) and in tissue (P <
1.1 * 10-4). This study reveals significant association between blood-based
decreased S100P methylation and BC, and provides another proof for the
application of altered DNA methylation signatures from blood cells as potential
markers for the detection of BC, especially for the early stage.
PMID- 28426875
TI - Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid
formation and resistance to EGFR pathway inhibition in estrogen receptor-negative
inflammatory breast cancer cells.
AB - Emerging evidence from epidemiological studies suggests a link between
environmental chemical exposure and progression of aggressive breast cancer
subtypes. Of all clinically distinct types of breast cancers, the most lethal
phenotypic variant is inflammatory breast cancer (IBC). Overexpression of
epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER)
negativity is common in IBC tumor cells, which instead of a solid mass present as
rapidly proliferating diffuse tumor cell clusters. Our previous studies have
demonstrated a role of an adaptive response of increased antioxidants in acquired
resistance to EGFR-targeting drugs in IBC. Environmental chemicals are known to
induce oxidative stress resulting in perturbations in signal transduction
pathways. It is therefore of interest to identify chemicals that can potentiate
EGFR mitogenic effects in IBC. Herein, we assessed in ER-negative IBC cells a
subset of chemicals from the EPA ToxCast set for their effect on EGFR activation
and in multiple cancer phenotypic assays. We demonstrated that endocrine
disrupting chemicals such as bisphenol A (BPA) and 2,2-bis(p-hydroxyphenyl)-1,1,1
trichloroethane can increase EGFR/ERK signaling. BPA also caused a corresponding
increase in expression of SOD1 and anti-apoptotic Bcl-2, key markers of
antioxidant and anti-apoptotic processes. BPA potentiated clonogenic growth and
tumor spheroid formation in vitro, reflecting IBC-specific pathological
characteristics. Furthermore, we identified that BPA was able to attenuate the
inhibitory effect of an EGFR targeted drug in a longer-term anchorage-independent
growth assay. These findings provide a potential mechanistic basis for
environmental chemicals such as BPA in potentiating a hyperproliferative and
death-resistant phenotype in cancer cells by activating mitogenic pathways to
which the tumor cells are addicted for survival.
PMID- 28426877
TI - Knockdown of hnRNPK leads to increased DNA damage after irradiation and reduces
survival of tumor cells.
AB - Radiotherapy is an important treatment option in the therapy of multiple tumor
entities among them head and neck squamous cell carcinoma (HNSCC). However, the
success of radiotherapy is limited by the development of radiation resistances.
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofactor of p53 and
represents a potential target for radio sensitization of tumor cells. In this
study, we analyzed the impact of hnRNPK on the DNA damage response after gamma
irradiation. By yH2AX foci analysis, we found that hnRNPK knockdown increases DNA
damage levels in irradiated cells. Tumor cells bearing a p53 mutation showed
increased damage levels and delayed repair. Knockdown of hnRNPK applied
simultaneously with irradiation reduced colony-forming ability and survival of
tumor cells. Taken together, our data shows that hnRNPK is a relevant modifier of
DNA damage repair and tumor cell survival. We therefore recommend further studies
to evaluate the potential of hnRNPK as a drug target for improvement of
radiotherapy success.
PMID- 28426876
TI - Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related
multistage hepatocarcinogenesis: comparison with hepatitis virus-related
carcinogenesis.
AB - The aim of this study was to clarify the significance of DNA methylation
alterations during non-alcoholic steatohepatitis (NASH)-related
hepatocarcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis
was performed on 264 liver tissue samples using the Illumina Infinium
HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed
significant DNA methylation alterations in 113 samples of non-cancerous liver
tissue showing NASH (NASH-N) as compared with 55 samples of normal liver tissue
(NLT). Principal component analysis using the 3331 probes revealed distinct DNA
methylation profiles of NASH-N samples that were different from those of NLT
samples and 37 samples of non-cancerous liver tissue showing chronic hepatitis or
cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection (viral-N). Receiver operating characteristic curve analysis identified
194 probes that were able to discriminate NASH-N samples from viral-N samples
with area under the curve values of more than 0.95. Jonckheere-Terptsra trend
test revealed that DNA methylation alterations in NASH-N samples from patients
without hepatocellular carcinoma (HCC) were inherited by or strengthened in NASH
N samples from patients with HCC, and then inherited by or further strengthened
in 22 samples of NASH-related HCC (NASH-T) themselves. NASH- and NASH-related HCC
specific DNA methylation alterations, which were not evident in viral-N samples
and 37 samples of HCC associated with HBV or HCV infection, were observed in
tumor-related genes, such as WHSC1, and were frequently associated with mRNA
expression abnormalities. These data suggested that NASH-specific DNA methylation
alterations may participate in NASH-related multistage hepatocarcinogenesis.
PMID- 28426878
TI - Microbiota, NASH, HCC and the potential role of probiotics.
AB - Hepatocellular carcinoma (HCC) accounts for the majority of primary liver
cancers. Clearly identifiable risk factors are lacking in up to 30% of HCC
patients and most of these cases are attributed to non-alcoholic fatty liver
disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Beyond the known risk
factors for NAFLD, the intestinal microbiota, in particular dysbiosis (defined as
any change in the composition of the microbiota commonly found in healthy
conditions) is emerging as a new factor promoting the development of chronic
liver diseases and HCC. Intestinal microbes produce a large array of bioactive
molecules from mainly dietary compounds, establishing an intense microbiota-host
transgenomic metabolism with a major impact on physiological and pathological
conditions. A better knowledge of these 'new' pathways could help unravel the
pathogenesis of HCC in NAFLD to devise new prevention strategies. Currently
unsettled issues include the relative role of a 'negative microbiota' (in
addition to the other known risk factors for NASH) and the putative prevention of
NAFLD through modulation of the gut microbiota.
PMID- 28426879
TI - Acute exposure to DEHP metabolite, MEHP cause genotoxicity, mutagenesis and
carcinogenicity in mammalian Chinese hamster ovary cells.
AB - Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production
of polyvinyl chloride, can be converted to the more potent metabolite mono
ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association
with elevated induction of rat hepatic cancer and reproductive toxicity in
response to MEHP exposure. However, the mechanism of genotoxicity and
carcinogenicity induced by MEHP treatment remains unclear. As a means to
elucidate the mechanisms of action, lethality and mutagenicity in the adenine
phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by
MEHP were assessed. Dose-response relationships were determined in the parental
AA8 cell line, its nucleotide repair-deficient UV5 and base repair-deficient EM9
subclones, and also in AS52 cells harboring the bacterial guanine-hypoxanthine
phosphoribosyltransferase (gpt) gene and its derived AS52-XPD-knockdown and AS52
PARP-1-knockdown cells. Treatment of AS52 with MEHP led to intracellular
production of reactive oxygen species (ROS) and DNA strand breaks in a dose
dependent manner. Separately, mutations in the gpt gene of AS52 cells were
characterized and found to be dominated by G:C to A:T and A:T to G:C transitions.
Independent AS52-mutant cell (ASMC) clones were collected for the sequential in
vivo xenograft tumorigenic studies, 4 of total 20 clones had aggressive tumor
growth. Moreover, microarray analysis indicated miR-let-7a and miR-125b
downregulated in ASMC, which might raise oncogenic MYC and RAS level and activate
ErbB pathway. Comparative evaluation of the results indicates that the principal
mechanism of this mutagenic action is probably to be through generation of ROS,
causing base excision damage resulting in carcinogenicity.
PMID- 28426880
TI - Surgeon Volume in Parathyroid Surgery-Surgical Efficiency, Outcomes, and
Utilization.
PMID- 28426881
TI - New-generation CZT cameras: the future of infection imaging?
PMID- 28426882
TI - From conventional to molecular imaging: delineating mechanisms, diagnosis, and
outcomes.
PMID- 28426883
TI - Challenges in the Management of Fungal Keratitis.
PMID- 28426885
TI - Prognostic implications of left ventricular global longitudinal strain in heart
failure patients with narrow QRS complex treated with cardiac resynchronization
therapy: a subanalysis of the randomized EchoCRT trial.
AB - Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic
function and correlates inversely with the extent of LV myocardial scar and
fibrosis. The present subanalysis of the Echocardiography Guided CRT trial
investigated the prognostic value of LV GLS in patients with narrow QRS complex.
Methods and results: Left ventricular (LV) global longitudinal strain (GLS) was
measured on the apical 2-, 4- and 3-chamber views using speckle tracking
analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with
cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median
value of LV GLS in the overall population was 7.9%, interquartile range 6.2
10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF
group and 111 in the CRT-ON group reached the combined primary endpoint of all
cause mortality and heart failure hospitalization. Each 1% absolute unit decrease
in LV GLS was independently associated with 11% increase in the risk to reach the
primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04-1.17, P <
0.001), after adjusting for ischaemic cardiomyopathy and randomization treatment
among other clinically relevant variables. When categorizing patients according
to quartiles of LV GLS, the primary endpoint occurred more frequently in patients
in the lowest quartile (<6.2%) treated with CRT-ON vs. CRT-OFF (45.6% vs. 28.7%,
P = 0.009) whereas, no differences were observed in patients with LV GLS >=6.2%
treated with CRT-OFF vs. CRT-ON (23.7% vs. 24.5%, respectively; P = 0.62).
Conclusion: Low LV GLS is associated with poor outcome in heart failure patients
with QRS width <130 ms, independent of randomization to CRT or not. Importantly,
in the group of patients with the lowest LV GLS quartile, CRT may have a
detrimental effect on clinical outcomes.
PMID- 28426887
TI - Frontiers in heart failure: sodium, longitudinal strain, contractility sensor,
fatal arrhythmias, and stroke.
PMID- 28426886
TI - Risk of stroke in chronic heart failure patients with preserved ejection
fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I
Preserve trials.
AB - Aims: The incidence and predictors of stroke in patients with heart failure and
preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are
unknown. We described the incidence of stroke in HF-PEF patients with and without
AF and predictors of stroke in those without AF. Methods and results: We pooled
data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we
derived a model for stroke in patients without AF in this cohort and compared its
performance with a published model in heart failure patients with reduced
ejection fraction (HF-REF)-predictive variables: age, body mass index, New York
Heart Association class, history of stroke, and insulin-treated diabetes. The two
stroke models were compared and Kaplan-Meier curves for stroke estimated. The
risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did
not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF
(rates 1.80 and 1.00 per 100 patient-years, respectively). There was no
difference in performance of the stroke model derived in the HF-PEF cohort and
the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs.
0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model
performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in
patients in the upper third of risk approximated to that in patients with AF
(1.60 and 1.80 per 100 patient-years, respectively). Conclusions: A small number
of clinical variables identify a subset of patients with HF-PEF, but without AF,
at elevated risk of stroke.
PMID- 28426888
TI - Adolescent Depression: Differential Symptom Presentations in Deaf and Hard-of
Hearing Youth Using the Patient Health Questionnaire-9.
AB - The present study examined differences in symptom presentation in screening for
pediatric depression via evaluation of the Patient Health Questionnaire-9 (PHQ
9). In particular, we examined whether PHQ-9 items function differentially among
deaf and hard-of-hearing (DHH; n = 75) and hearing (n = 75) youth based on
participants recruited from crisis assessment services. Multiple indicators
multiple causes models were used to examine whether items of the PHQ-9 functioned
differently between groups as well as whether there were group differences in the
mean severity of depressive symptoms. Results indicate that DHH youth were more
likely to endorse psychosomatic items, and less likely to endorse an affective
item. These findings indicate that the PHQ-9 functions differently when used with
DHH youth. Implications of these findings are discussed, including both for
future work with the PHQ-9 and with regard to the conceptualization of depression
across hearing groups.
PMID- 28426889
TI - Concurrent and Longitudinal Predictors of Reading for Deaf and Hearing Children
in Primary School.
AB - Forty-one children with severe-profound prelingual hearing loss were assessed on
single word reading, reading comprehension, English vocabulary, phonological
awareness and speechreading at three time points, 1 year apart (T1-T3). Their
progress was compared with that of a group of hearing children of similar
nonverbal IQ, initially reading at the same level. Single word reading improved
at each assessment point for the deaf children but there was no growth in reading
comprehension from T2 to T3. There were no differences between children with
cochlear implants and those with hearing aids on either reading measure but
orally educated children had higher scores than children who signed in the
classroom. English vocabulary and speechreading were the most consistent
longitudinal predictors of reading for the deaf children. Phonological awareness
was the most consistent longitudinal predictor for the hearing group and also a
concurrent predictor of reading at T3 for both groups. There were many more
significant correlations among the various measures for the deaf children than
the hearing at both T1 and T3, suggesting that skills underpinning reading,
including phonological awareness and vocabulary, are more closely related for
deaf children. Implications of these findings for of deaf children's literacy are
explored.
PMID- 28426891
TI - Experiences of nurses with the care of patients with dementia in acute hospitals:
A secondary analysis.
AB - AIMS AND OBJECTIVES: To describe nurses' experiences in caring for people with
dementia in acute hospital settings. BACKGROUND: Recent research suggests that
nurses' experience in caring for people with dementia in acute hospitals is
characterised by frustration, overall job dissatisfaction and feelings of
powerlessness and guilt. Despite a growing body of knowledge concerning the care
of people with dementia in acute care settings, it remains unclear how nurses in
acute hospitals provide care for people with dementia and what general conditions
characterise the nursing care provided to these patients. DESIGN: A qualitative
secondary analysis was conducted. METHODS: Data were collected using audio
recorded focus group discussions with nurses in Germany and Austria. Overall, 12
focus group discussions, which were part of two larger research projects in
Germany and Austria, were expanded into a qualitative secondary analysis (a
content analysis). RESULTS: The findings show that nurses face great uncertainty
in caring for people with dementia in acute hospital settings and that each nurse
reacts in different ways to address this uncertainty. The results also underline
that, even for nurses who provide some form of person-centred care, the hospital
environment imposes several contextual constraints. CONCLUSIONS: Hospitals must
minimise constraints to give every nurse the chance to perform person-centred
care. Furthermore, it is important to sensitise nurses and give them sufficient
training and education to enable them to care for people with dementia. RELEVANCE
TO CLINICAL PRACTICE: The results may contribute to a better understanding of the
factors that support or constrain person-centred nursing care for people with
dementia in acute hospitals.
PMID- 28426893
TI - Diffuse normolipemic plane xanthoma on striae.
PMID- 28426892
TI - "I am still passionate despite the challenges": Nurses navigating the care for
refugees.
AB - AIMS AND OBJECTIVES: To report the challenges faced by the nursing workforce in
refugee health. BACKGROUND: Nurses are in the forefront of care provision for
refugees who are recognised as one of the most vulnerable population groups in
the world. The number of refugees in Australia is increasing, and more nurses are
needed as care providers. Research on the challenges faced by refugee health
nurses is sparse. DESIGN: Qualitative research methodology was used to study the
experience of refugee health nurses. Using a descriptive qualitative research
approach, a better understanding of the ongoing challenges of caring for refugees
is presented. METHOD: Semi-structured interview with a convenience sample of
registered nurses who worked in New South Wales refugee health services was
conducted and digitally recorded in 2013. Responses were transcribed verbatim and
analysed for themes. RESULTS: Six refugee health nurses who have been working in
New South Wales refugee health services between 1-8 years participated in this
study. A thematic analysis of the data led to three main themes: caring for
clients with challenging needs; challenges in the course of caring for refugees;
and passion in caring for refugees. Participants reported what it means to be
refugee health nurses, they explored their roles and emphasised the need to
understand refugee health issues. CONCLUSIONS: This study provides more insight
into the unique experiences nurses have when caring for refugees. More debriefing
opportunities and resources may reduce the challenges of caring. RELEVANCE TO
CLINICAL PRACTICE: The refugee health nurses' stories support the need for
further role refinement for nurses caring for refugees in the community, rural
areas and health clinics. This is essential in promoting their well-being and
that of the vulnerable population they are caring for.
PMID- 28426890
TI - Fine-mapping of lipid regions in global populations discovers ethnic-specific
signals and refines previously identified lipid loci.
AB - Genome-wide association studies have identified over 150 loci associated with
lipid traits, however, no large-scale studies exist for Hispanics and other
minority populations. Additionally, the genetic architecture of lipid-influencing
loci remains largely unknown. We performed one of the most racially/ethnically
diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date
using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African
Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians.
The majority of signals found in these groups generalize to European Americans.
While we uncovered signals unique to racial/ethnic populations, we also observed
systematically consistent lipid associations across these groups. In African
Americans, we identified three novel signals associated with HDL-C (LPL, APOA5,
LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this
population, we refined the location for 16 out of the 58 known MetaboChip lipid
loci. These results can guide tailored screening efforts, reveal population
specific responses to lipid-lowering medications, and aid in the development of
new targeted drug therapies.
PMID- 28426894
TI - Characteristics and Course of Enthesitis in a Juvenile Idiopathic Arthritis
Inception Cohort.
AB - OBJECTIVE: To describe the prevalence, associated characteristics, and course of
enthesitis in a juvenile idiopathic arthritis (JIA) inception cohort. METHODS:
Canadian children newly diagnosed with JIA between 2005 and 2010 were categorized
using International League of Associations for Rheumatology criteria at the 6
month visit and followed in the Research in Arthritis in Canadian Children
Emphasizing Outcomes (ReACCh-Out) cohort for up to 5 years. The presence of
entheseal tenderness on examination at 33 sites shown on a homunculus was
recorded at 0, 6, 12, 18, 24, 36, 48, and 60 months after enrollment. Enthesitis
was defined as entheseal tenderness at more than 1 site or on more than 1
occasion. Analyses consisted of descriptive statistics and linear mixed models
for longitudinal data. RESULTS: Of 1,406 patients, 219 (16%) had enthesitis and,
of those with enthesitis, 141 (64%) were classified as having enthesitis-related
arthritis (ERA). Children with enthesitis were more often older (10.7 versus 7.5
years), male (57% versus 31%), and with polyarthritis (57% versus 41%) and
sacroiliac involvement (30% versus 4%). Entheseal tenderness was most frequent at
the calcaneal plantar fascial insertion (39%), Achilles tendon insertion (31%),
and tibial tuberosity (30%). The mean number of tender entheseal sites decreased
in parallel with active joint counts. There was no difference in active joint
counts over time in children with or without enthesitis (P = 0.73). CONCLUSION:
Enthesitis was observed in 16% of patients with JIA, but only two thirds were
categorized as having ERA. Contrary to expectations, most children with
enthesitis had polyarticular involvement. The course of enthesitis paralleled the
course of active joint counts.
PMID- 28426896
TI - A note on marginalization of regression parameters from mixed models of binary
outcomes.
AB - This article discusses marginalization of the regression parameters in mixed
models for correlated binary outcomes. As is well known, the regression
parameters in such models have the "subject-specific" (SS) or conditional
interpretation, in contrast to the "population-averaged" (PA) or marginal
estimates that represent the unconditional covariate effects. We describe an
approach using numerical quadrature to obtain PA estimates from their SS
counterparts in models with multiple random effects. Standard errors for the PA
estimates are derived using the delta method. We illustrate our proposed method
using data from a smoking cessation study in which a binary outcome (smoking,
Y/N) was measured longitudinally. We compare our estimates to those obtained
using GEE and marginalized multilevel models, and present results from a
simulation study.
PMID- 28426897
TI - The effects of awareness and count duration on adult respiratory rate
measurements: An experimental study.
AB - AIMS AND OBJECTIVES: To investigate whether awareness of manual respiratory rate
monitoring affects respiratory rate in adults, and whether count duration
influences respiratory rate estimates. BACKGROUND: Nursing textbooks typically
suggest that the patient should ideally be unaware of respiratory rate
observations; however, there is little published evidence of the effect of
awareness on respiratory rate, and none specific to manual measurement. In
addition, recommendations about the length of the respiratory rate count vary
from text to text, and the relevant empirical evidence is scant, inconsistent and
subject to substantial methodological limitations. DESIGN: Experimental study
with awareness of respiration monitoring (aware, unaware; randomised between
subjects) and count duration (60 s, 30 s, 15 s; within-subjects) as the
independent variables. Respiratory rate (breaths/minute) was the dependent
variable. METHODS: Eighty-two adult volunteers were randomly assigned to aware
and unaware conditions. In the baseline block, no live monitoring occurred. In
the subsequent experimental block, the researcher informed aware participants
that their respiratory rate would be counted, and did so. Respirations were
captured throughout via video recording, and counted by blind raters viewing 60-,
30- and 15-s extracts. The data were collected in 2015. RESULTS: There was no
baseline difference between the groups. During the experimental block, the
respiratory rates of participants in the aware condition were an average of 2.13
breaths/minute lower compared to unaware participants. Reducing the count
duration from 1 min to 15 s caused respiratory rate to be underestimated by an
average of 2.19 breaths/minute (and 0.95 breaths/minute for 30-s counts). The
awareness effect did not depend on count duration. CONCLUSIONS: Awareness of
monitoring appears to reduce respiratory rate, and shorter monitoring durations
yield systematically lower respiratory rate estimates. RELEVANCE TO CLINICAL
PRACTICE: When interpreting and acting upon respiratory rate data, clinicians
should consider the potential influence of these factors, including cumulative
effects.
PMID- 28426895
TI - Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial
Lung Disease Associated With Systemic Sclerosis.
AB - OBJECTIVE: To determine the prognostic value of pulmonary function test (PFT)
trends at 1 and 2 years in interstitial lung disease (ILD) associated with
systemic sclerosis (SSc). METHODS: The prognostic significance of PFT trends at 1
year (n = 162) and 2 years (n = 140) was examined against 15-year survival in
patients with SSc-associated ILD. PFT trends, expressed as continuous change and
as categorical change in separate analyses, were examined against mortality in
univariate and multivariate models. SSc-associated ILD was defined at
presentation as either limited lung fibrosis or extensive lung fibrosis, using
the United Kingdom Raynaud's and Scleroderma Association severity staging system.
RESULTS: One-year PFT trends were predictive of mortality only in patients with
extensive lung fibrosis: categorical change in the forced vital capacity (FVC),
alone or in combination with categorical change in the diffusing capacity for
carbon monoxide (DLco), had greater prognostic significance than continuous
change in the FVC or trends in other PFT variables. Taking into account both
prognostic value and sensitivity to change, the optimal definition of progression
for trial purposes was an FVC and DLco composite end point, consisting of either
an FVC decline from baseline of >=10% or an FVC decline of 5-9% in association
with a DLco decline of >=15%. At 2 years, gas transfer trends had the greatest
prognostic significance, in the whole cohort and in those with limited lung
fibrosis. However, in patients with extensive lung fibrosis, the above-defined
FVC and DLco composite end point was the strongest prognostic determinant. Larger
changes in the FVC:DLco ratio than in the carbon monoxide transfer coefficient
were required to achieve prognostic significance. CONCLUSION: Based on linkages
to long-term outcomes, these findings provide support for use of routine
spirometry and gas transfer monitoring in patients with SSc-associated ILD, with
further evaluation of a composite FVC and DLco end point warranted for trial
purposes.
PMID- 28426898
TI - Improving myoblast differentiation on electrospun poly(epsilon-caprolactone)
scaffolds.
AB - Polymer scaffolds are used as an alternative to support tissue regeneration when
it does not occur on its own. Cell response on polymer scaffolds is determined by
factors such as polymer composition, topology, and the presence of other
molecules. We evaluated the cellular response of murine skeletal muscle myoblasts
on aligned or unaligned fibers obtained by electrospinning poly(epsilon
caprolactone) (PCL), and blends with poly(lactic-co-glycolic acid) (PLGA) or
decorin, a proteoglycan known to regulate myogenesis. The results showed that
aligned PCL fibers with higher content of PLGA promote cell growth and improve
the quality of differentiation with PLGA scaffolds having the highest confluence
at over 68% of coverage per field of view for myoblasts and more than 7% of
coverage for myotubes. At the same time, the addition of decorin greatly improves
the quantity and quality of differentiated cells in terms of cell fusion, myotube
length and thickness, being 71, 10, and 51% greater than without the protein,
respectively. Interestingly, our results suggest that at certain concentrations,
the effect of decorin on myoblast differentiation exceeds the topological effect
of fiber alignment. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
105A: 2241-2251, 2017.
PMID- 28426899
TI - Ultrasonographic features of intravascular fasciitis: case report and review of
the literature.
PMID- 28426900
TI - Videodermoscopy supports the diagnosis of eyelash trichotillomania.
PMID- 28426901
TI - A case of toxic epidermal necrolysis and vanishing bile duct syndrome, requiring
liver transplantation.
PMID- 28426902
TI - Hepatic steatosis after pediatric liver transplant.
AB - Hepatic steatosis develops after liver transplantation (LT) in 30% of adults, and
nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease
in nontransplanted children. However, posttransplant steatosis has been minimally
studied in pediatric LT recipients. We explored the prevalence, persistence, and
association with chronic liver damage of hepatic steatosis in these children. In
this single-center study of pediatric patients transplanted 1988-2015 (n = 318),
31% of those with any posttransplant biopsy (n = 271) had >= 1 biopsy with
steatosis. Median time from transplant to first biopsy with steatosis was 0.8
months (interquartile range [IQR], 0.3-6.5 months) and to last biopsy with
steatosis was 5.5 months (IQR, 1.0-24.5 months); 85% of patients with steatosis
also had for-cause biopsies without steatosis. All available for-cause biopsies
were re-evaluated (n = 104). Of 9 biopsies that could be interpreted as
nonalcoholic steatohepatitis (NASH)/borderline NASH, with steatosis plus
inflammation or ballooning, 8 also had features of cholestasis or rejection.
Among 70 patients with surveillance biopsies 3.6-20.0 years after transplant,
only 1 overweight adolescent had a biopsy with NAFLD (grade 1 steatosis, mild
inflammation, no ballooning or fibrosis)-despite a 30% prevalence of
overweight/obesity in the cohort and 27% with steatosis on previous for-cause
biopsy. Steatosis on preceding for-cause biopsy was not associated with portal (P
= 0.49) or perivenular fibrosis (P = 0.85) on surveillance biopsy. Hepatic
steatosis commonly develops early after transplant in children and adolescents,
but it rarely persists. Biopsies that did have steatosis with NASH
characteristics were all for-cause, mostly in patients with NAFLD risk factors
and/or confounding causes of liver damage. Prospective studies that follow
children into adulthood will be needed to evaluate if and when hepatic steatosis
presents a longterm risk for pediatric LT recipients. Liver Transplantation 23
957-967 2017 AASLD.
PMID- 28426903
TI - The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated
Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical
Trial.
AB - OBJECTIVE: To assess the therapeutic efficacy of local injections of botulinum
toxin type A (Btx-A) in improving blood flow to the hands of patients with
Raynaud's phenomenon (RP) secondary to scleroderma. METHODS: In this randomized,
double-blind, placebo-controlled clinical trial, patients with scleroderma
associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly
selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1
and 4 months postinjection included laser Doppler imaging of hands, patient
reported outcomes, and physical examination. We compared outcomes using paired t
tests and population-average generalized models with generalized estimating
equations. RESULTS: Of 40 patients enrolled, 25 had limited scleroderma and 15
had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater
reduction in average blood flow in Btx-A-treated hands compared to placebo
treated hands. The model estimated that this difference was statistically
significant (average difference -30.08 flux units [95% confidence interval
56.19, -3.98], P for interaction = 0.024). This difference was mainly influenced
by patients with longstanding RP and diffuse scleroderma. Change in blood flow at
4-month follow-up was not significantly different between groups. Clinical
measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog
scale, and Raynaud's Condition Score) improved slightly for Btx-A-treated hands.
CONCLUSION: Our laboratory-based laser Doppler imaging flow data do not support
using Btx-A to treat RP in all scleroderma patients. The secondary clinical
outcomes suggest some positive effect, but its clinical meaningfulness is
questionable. The role of Btx-A in treating RP should be further studied with
more homogeneous patient populations and in unique clinical situations such as
acute digital ischemia.
PMID- 28426904
TI - In vitro study of the proliferation and growth of human fetal osteoblasts on Mg
and Si co-substituted tricalcium phosphate ceramics.
AB - The objective of this work was to study the feasibility of the solid state
sintering, a conventional ceramic processing method, to obtain Mg and Si co
substituted tricalcium phosphate bioceramics and composites containing diopside.
A series of new Ca3 (PO4 )2 based ceramics has been prepared from attrition
milled mixtures of synthetic Ca3 (PO4 )2 and CaMg(SiO3 )2 powders, isostatically
pressed and sintered at 1250-1300 degrees C. Materials containing 0, 1, and 5 wt
% of CaMg(SiO3 )2 were constituted by beta + alpha - Ca3 (PO4 )2 solid solutions
while the material containing 60 wt % of CaMg(SiO3 )2 was a constituted by beta-
Ca3 (PO4 )2 and CaMg(SiO3 )2 . The biological responses of the developed ceramics
were studied in vitro using human fetal osteoblast cultures. Culture times ranged
from 1 to 21 days. The new family of materials promotes the adhesion and
proliferation of human osteoblasts cultured onto their surface forming a
monolayer and showing a normal morphology. The results of the MTT and Alamar Blue
assays showed that the soluble components extracted from the Mg/Si- co
substituted Ca3 (PO4 )2 and the Ca3 (PO4 )2 -CaMg(SiO3 )2 composite were
noncytotoxic. The specimens with diopside exhibited a better in vitro behavior
which is attributed to the release of Si and Mg ions to the culture medium,
enhancing the activity of cells. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
Res Part A: 105A: 2266-2275, 2017.
PMID- 28426905
TI - Acantholytic dyskeratotic acanthoma: a possible skin adverse event of vemurafenib
treatment.
PMID- 28426906
TI - Measuring the impact of dermatological conditions on family and caregivers: a
review of dermatology-specific instruments.
AB - The patient is the centre of a web of relationships, and the impact of his/her
disease on family members and caregivers must be taken into account. The aim of
this study was to identify the specific instruments that measure the impact of a
dermatological disease on the quality of life (QoL) of family members, by
performing a systematic search of the literature. Fifteen papers were identified,
describing the creation and validation of nine instruments. Four of them
concerned atopic dermatitis (Dermatitis Family Index, DFI; Parents' Index QoL
Atopic Dermatitis, PiQoL-AD; QoL in primary caregivers of children with atopic
dermatitis, QPCAD; Childhood Atopic Dermatitis Impact Scale, CADIS), two measured
the impact of psoriasis in family members (Psoriasis Family Index, PFI;
FamilyPso), one the impact of epidermolysis bullosa (Epidermolysis Bullosa Burden
of Disease, EB-BoD), one of ichthyosis (Family Burden Ichthyosis, FBI), and one
was generic for dermatological conditions (Family Dermatology Life Quality Index,
FDLQI). The European Academy of Dermatology and Venereology quality of life
taskforce recommends that the impact of a skin disease on family and caregivers
should be measured as part of any thorough evaluation of the burden of a disease.
Guidelines are given to choose the most appropriate instruments.
PMID- 28426907
TI - Frontal fibrosing alopecia: clinical and prognostic classification.
AB - BACKGROUND: Frontal fibrosing alopecia (FFA) is a chronic scarring alopecia with
an unpredictable evolution. There are no current classifications of this disease
that may predict its prognosis. OBJECTIVE: To analyse the differences in clinical
presentation and evolution of FFA patients and to create a clinical and
prognostic classification. METHODS: We conducted a retrospective analytical study
of FFA patients. Clinical characteristics of frontal hairline recession were used
as the sorting variable between patterns of presentation. A cohort of 106
patients homogenously treated with oral dutasteride and topical corticosteroid
was followed 12 months. RESULTS: In all, 242 female patients with a mean age of
61.4 years were included. Patients were classified into three clinical patterns
[118 (48.8%) patients as pattern I (linear), 109 patients (45%) as pattern II
(diffuse) and 15 patients (6.2%) as pattern III (double line)]. Stabilization was
achieved in 37.3% of the 106 patients treated with oral dutasteride and topical
corticosteroid. Pattern III patients had less hairline recession and eyebrow
involvement at the diagnosis and after treatment. LIMITATIONS: Retrospective
design. CONCLUSIONS: Frontal fibrosing alopecia patients can be classified into
three different clinical patterns with different prognosis. Pattern III patients
have the best prognosis, while pattern II patients have the worst prognosis.
PMID- 28426908
TI - Clinically useful brain imaging for neuropsychiatry: How can we get there?
AB - Despite decades of research, visions of transforming neuropsychiatry through the
development of brain imaging-based "growth charts" or "lab tests" have remained
out of reach. In recent years, there is renewed enthusiasm about the prospect of
achieving clinically useful tools capable of aiding the diagnosis and management
of neuropsychiatric disorders. The present work explores the basis for this
enthusiasm. We assert that there is no single advance that currently has the
potential to drive the field of clinical brain imaging forward. Instead, there
has been a constellation of advances that, if combined, could lead to the
identification of objective brain imaging-based markers of illness. In
particular, we focus on advances that are helping to (1) elucidate the research
agenda for biological psychiatry (e.g., neuroscience focus, precision medicine),
(2) shift research models for clinical brain imaging (e.g., big data exploration,
standardization), (3) break down research silos (e.g., open science, calls for
reproducibility and transparency), and (4) improve imaging technologies and
methods. Although an arduous road remains ahead, these advances are repositioning
the brain imaging community for long-term success.
PMID- 28426909
TI - Nursing and pharmacy students' use of emotionally intelligent behaviours to
manage challenging interpersonal situations with staff during clinical placement:
A qualitative study.
AB - AIMS AND OBJECTIVES: To identify challenging interpersonal interactions
experienced by nursing and pharmacy students during clinical placement, and
strategies used to manage those situations. BACKGROUND: Healthcare students and
staff experience elevated stress when exposed to dynamic clinical environments,
complex care and challenging professional relationships. Emotionally intelligent
behaviours are associated with appropriate recognition and management of emotions
evoked by stressful experiences and development of effective relationships.
Nursing and pharmacy students' use of emotionally intelligent behaviours to
manage challenging interpersonal situations is not well known. DESIGN: A
qualitative design, using semi-structured interviews to explore experiences of
challenging interpersonal situations during clinical placement (Phase two of a
larger mixed-methods study). Final-year Australian university nursing and
pharmacy students (n = 20) were purposefully recruited using a range of Emotional
Intelligence scores (derived in Phase one), measured using the GENOS Emotional
intelligence Inventory (concise version). RESULTS: Challenging interpersonal
situations involving student-staff and intrastaff conflict, discourteous
behaviour and criticism occurred during clinical placement. Students used
personal and relational strategies, incorporating emotionally intelligent
behaviours, to manage these encounters. Strategies included reflecting and
reframing, being calm, controlling discomfort and expressing emotions
appropriately. CONCLUSIONS: Emotionally intelligent behaviours are effective to
manage stressful interpersonal interactions. Methods for strengthening these
behaviours should be integrated into education of nursing and pharmacy students
and qualified professionals. Education within the clinical/workplace environment
can incorporate key interpersonal skills of collaboration, social interaction and
reflection, while also attending to sociocultural contexts of the healthcare
setting. RELEVANCE TO CLINICAL PRACTICE: Students and staff are frequently
exposed to stressful clinical environments and challenging interpersonal
encounters within healthcare settings. Use of emotionally intelligent behaviours
to recognise and effectively manage these encounters may contribute to greater
stress tolerance and enhanced professional relationships. Nursing and pharmacy
students, and their qualified counterparts, need to be educated to strengthen
their emotional intelligence skills.
PMID- 28426910
TI - Family and Other Unpaid Caregivers and Older Adults with and without Dementia and
Disability.
AB - OBJECTIVES: To estimate the number of caregivers providing assistance to
community-dwelling older persons with and without dementia and with or without
substantial disability; to describe the characteristics of caregivers and care
recipients in these groups; to characterize the health-related tasks that
caregivers provide; and to estimate associations between the numbers of tasks and
caregiver burden. DESIGN: Nationally representative surveys of caregivers and
older adults in the United States. SETTING: 2011 National Health and Aging Trends
Study and National Study of Caregiving. PARTICIPANTS: Community-dwelling older
adults and their family caregivers, who were selected on the basis of having
assisted with mobility, self-care, household activities, transportation, or
medical tasks. MEASUREMENTS: Caregiver burden (emotional, physical, financial
difficulties) and restrictions on social participation. RESULTS: Although much
larger proportions of older adults with dementia and disability (98.4%, n = 1.0
million) and dementia but not disability (95.5%, n = 1.3 million) received
caregiving assistance, the largest absolute number of individuals receiving
assistance were older adults without dementia or disability (4.0 million). Within
each caregiver group, caregivers provided assistance with at least one task
across domains of activity of daily living and instrumental activity of daily
living-related assistance (>98%), health systems logistics (>70%), and health
management (>50%). There was a significant linear association between number of
tasks provided and risk of burden in virtually all caregiver groups and domains
of assistance. CONCLUSION: Caregivers of care recipients without dementia or
disability accounted for the largest absolute number of helpers. These
caregivers, similar to caregivers of care recipients with dementia or disability,
delivered a broad spectrum of health-related tasks and experienced caregiver
burden and restrictions on social participation. Findings support the need for
interventions that address the needs of caregivers who have not typically been
defined as high risk.
PMID- 28426912
TI - Association Between Inflammatory Back Pain Characteristics and Magnetic Resonance
Imaging Findings in the Spine and Sacroiliac Joints.
AB - OBJECTIVE: To investigate the association between magnetic resonance imaging
(MRI) findings at the sacroiliac (SI) joints and vertebral endplates and pain
characteristics assumed to be indicative of axial inflammation. METHODS: Patients
ages 18-40 years with persistent low back pain referred to an outpatient spine
clinic participated, including an unknown proportion of axial spondyloarthritis
patients. Data included MRI of the spine and SI joints and self-reported
responses to questions covering the Calin, Berlin, Assessment of
Spondyloarthritis International Society, and Bailly inflammatory back pain (IBP)
definitions. RESULTS: In the 1,020 included patients, 53% were women, and the
median age was 33 years. Positive associations were found between the SI joint
MRI findings and pain characteristics, odds ratios ranging from 1.4 to 2.7. SI
joint bone marrow edema (BME) was associated with morning stiffness >60 minutes,
and SI joint erosions with the Calin, Berlin, and Bailly IBP definitions,
alternating buttock pain, and good response to nonsteroidal antiinflammatory
drugs. SI joint fatty marrow deposition (FMD) was associated with insidious
onset, and SI joint sclerosis with pain at night. In addition, the spinal MRI
changes were associated with IBP, odds ratios ranging from 1.4 to 2.0; vertebral
endplate BME was associated with morning stiffness, and vertebral endplate FMD
with the Calin and Bailly IBP definitions, improvement with exercise, morning
stiffness >30 minutes, and pain worst in the morning. CONCLUSION: The identified
associations between inflammatory MRI findings and pain characteristics indicate
that axial inflammation to some degree induces a specific pain pattern. Thus, the
results add to knowledge of axial inflammatory processes. However, all identified
associations were weak, which compromises the use of IBP as a marker of axial
inflammation.
PMID- 28426911
TI - Brief Report: Blockade of TANK-Binding Kinase 1/IKKE Inhibits Mutant Stimulator
of Interferon Genes (STING)-Mediated Inflammatory Responses in Human Peripheral
Blood Mononuclear Cells.
AB - OBJECTIVE: Gain-of-function mutations in TMEM173, encoding the stimulator of
interferon (IFN) genes (STING) protein, underlie a novel type I interferonopathy
that is minimally responsive to conventional immunosuppressive therapies and
associated with high frequency of childhood morbidity and mortality. STING gain
of-function causes constitutive oversecretion of IFN. This study was undertaken
to determine the effects of a TANK-binding kinase 1 (TBK-1)/IKKE inhibitor
(BX795) on secretion and signaling of IFN in primary peripheral blood mononuclear
cells (PBMCs) from patients with mutations in STING. METHODS: PBMCs from 4
patients with STING-associated disease were treated with BX795. The effect of
BX795 on IFN pathways was assessed by Western blotting and an IFNbeta reporter
assay, as well as by quantification of IFNalpha in cell lysates, staining for
STAT-1 phosphorylation, and measurement of IFN-stimulated gene (ISG) messenger
RNA (mRNA) expression. RESULTS: Treatment of PBMCs with BX795 inhibited the
phosphorylation of IFN regulatory factor 3 and IFNbeta promoter activity induced
in HEK 293T cells by cyclic GMP-AMP or by genetic activation of STING. In vitro
exposure to BX795 inhibited IFNalpha production in PBMCs of patients with STING
associated disease without affecting cell survival. In addition, BX795 decreased
STAT-1 phosphorylation and ISG mRNA expression independent of IFNalpha blockade.
CONCLUSION: These findings demonstrate the effect of BX795 on reducing type I IFN
production and IFN signaling in cells from patients with gain-of-function
mutations in STING. A combined inhibition of TBK-1 and IKKE therefore holds
potential for the treatment of patients carrying STING mutations, and may also be
relevant in other type I interferonopathies.
PMID- 28426913
TI - Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid
Arthritis.
AB - OBJECTIVE: To examine associations of body mass index (BMI) and weight loss with
cause-specific mortality in rheumatoid arthritis (RA). METHODS: A cohort of US
veterans with RA was followed until death or through 2013. BMI was categorized as
underweight, normal, overweight, and obese. Weight loss was calculated as the 1)
annualized rate of change over the preceding 13 months, and 2) cumulative
percent. Vital status and cause of death were obtained from the National Death
Index. Multivariable competing-risks regression models were utilized to assess
the time-varying associations of BMI and weight loss with cause-specific
mortality. RESULTS: Among 1,600 participants and 5,789 patient-years of followup,
303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The
highest weight-loss rate and weight-loss percent were associated with a higher
risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27
[95% confidence interval (95% CI) 1.61-3.19]; percent: sHR 2.31 [95% CI 1.06
5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11-5.01]; percent: sHR 1.90
[95% CI 1.00-3.62]). Overweight BMI was protective of cardiovascular mortality
(sHR 0.59 [95% CI 0.38-0.91]), while underweight BMI was associated with a near 3
fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28-6.67]).
Incorporation of time-varying BMI and weight loss in the same models did not
substantially alter individual associations for cardiovascular and cancer
mortality, but an association between weight-loss percentage and respiratory
mortality was attenuated after BMI adjustment. CONCLUSION: Both BMI and weight
loss are predictors of cause-specific mortality in RA. Weight loss is a strong
predictor of cardiovascular and cancer mortality, while underweight BMI is a
stronger predictor of respiratory mortality.
PMID- 28426914
TI - The recommended dose of idarucizumab may not always be sufficient for sustained
reversal of dabigatran.
AB - : Essentials Reversal of anticoagulant effects of dabigatran may occur despite
application of idarucizumab. Monitoring of dabigatran level after antidote
application is crucial to detect rebound. Repeated doses of idarucizumab may be
necessary in cases of massive dabigatran accumulation. Combination of antidote
application and renal replacement therapy may offer additional benefit. SUMMARY:
Idarucizumab is a monoclonal antibody fragment designed for reversing the
anticoagulant effects of dabigatran. Administration is recommended as two
intravenous boluses of 2.5 g within 15 min of each other or as a single 5 g
bolus. However, in certain situations a second dose of the drug could be
necessary. We report the case of a 77-year-old man, treated with dabigatran for
paroxysmal atrial fibrillation. He presented at our department with acute renal
failure, concomitant massive dabigatran accumulation and subsequent acute
gastrointestinal bleeding. Fifty minutes after the administration of
idarucizumab, the dabigatran plasma concentration decreased from a peak of 1630
ng ml-1 to a level below the detection limit of 30 ng ml-1 and bleeding stopped.
Eight hours after administration, the dabigatran plasma level started to increase
up to 1560 ng ml-1 (96% of the maximum value obtained), accompanied by a further
drop in hemoglobin. Concomitant hemodialysis and hemofiltration led to a
continuous decrease in dabigatran plasma levels. However, sepsis and multiorgan
failure ensued, which led to death. With this case report we raise the question
of whether massive dabigatran accumulation requires repeated doses of
idarucizumab, or alternatively, if the combination of antidote with
hemodialysis/renal replacement therapy is advisable in order to remove
circulating levels of dabigatran.
PMID- 28426915
TI - Improvements in Colorectal Cancer Incidence Not Experienced by Nonmetropolitan
Women: A Population-Based Study From Utah.
AB - PURPOSE: Little is known about disparities in colorectal cancer (CRC) incidence
and mortality by community-level factors such as metropolitan status. METHODS:
This analysis utilized data from the Surveillance, Epidemiology, and End Results
(SEER) program from Utah. We included patients diagnosed with CRC from 1991 to
2010. To determine whether associations existed between
metropolitan/nonmetropolitan county of residence and CRC incidence, Poisson
regression models were used. CRC mortality was assessed using multivariable Cox
regression models. FINDINGS: CRC incidence rates did not differ between
metropolitan and nonmetropolitan counties by gender (males: 46.2 per 100,000 vs
45.1 per 100,000, P = .87; females: 34.4 per 100,000 vs 36.1 per 100,000, P =
.70). However, CRC incidence between the years of 2006 and 2010 in
nonmetropolitan counties was significantly higher in females (metropolitan: 30.4
vs nonmetropolitan: 37.0 per 100,000, P = .002). As compared to metropolitan
counties, the incidence of unstaged CRC in nonmetropolitan counties was
significantly higher in both males (1.7 vs 2.8 per 100,000, P = .003) and females
(1.4 vs 1.6 per 100,000, P = .002). Among patients who were diagnosed between
2006 and 2010, metropolitan counties were found to have significantly increased
survival among males and females, but nonmetropolitan counties showed increased
survival only for males. CONCLUSIONS: While we observed a decreasing incidence of
CRC among men and women in Utah, this effect was not seen in women in
nonmetropolitan areas nor among those with unstaged disease. Further studies
should evaluate factors that may account for these differences. This analysis can
inform interventions with a focus on women in nonmetropolitan areas.
PMID- 28426916
TI - Preconcentration and determination of 2-mercaptobenzimidazole by dispersive
liquid-liquid microextraction and experimental design.
AB - A method was developed to determine 2-mercaptobenzimidazole in water and urine
samples using dispersive liquid-liquid microextraction technique coupled with
ultraviolet-visible spectrophotometry. It was essential to peruse the effect of
all parameters that can likely influence the performance of extraction. The
influence of parameters, such as dispersive and extraction solvent volume and
sample volume, on dispersive liquid-liquid microextraction was studied. The
optimization was carried out by the central composite design method. The central
composite design optimization method resulted in 1.10 mL dispersive solvent,
138.46 MUL extraction solvent, and 4.46 mL sample volume. Under the optimal
terms, the calibration curve was linear over the range of 0.003-0.18 and 0.007
0.18 MUg/mL in water and urine samples, respectively. The limit of detection and
quantification of the proposed approach for 2-mercaptobenzimidazole were 0.013
and 0.044 MUg/mL in water samples and 0.016 and 0.052 MUg/mL in urine samples,
respectively. The method was successfully applied to determination of 2
mercaptobenzimidazole in urine and water samples.
PMID- 28426917
TI - Internet Cognitive-Behavioral Therapy for Depression in Older Adults With Knee
Osteoarthritis: A Randomized Controlled Trial.
AB - OBJECTIVE: To determine the efficacy of an internet-based cognitive-behavioral
therapy (iCBT) program for depression in older adults with osteoarthritis (OA) of
the knee and comorbid major depressive disorder (MDD). METHODS: We conducted a
randomized controlled trial in 69 adults (ages >=50 years) meeting criteria for
MDD and OA of the knee with 1-week postintervention (week 11) and 3-month
followup (week 24) end points. Patients were allocated to either a 10-week iCBT
program for depression added to treatment as usual (TAU) or to a TAU control
group. Primary outcomes were depression symptoms (9-Item Patient Health
Questionnaire [PHQ-9]) and psychological distress (Kessler-10 [K-10]). Secondary
outcomes included arthritis self-efficacy (Arthritis Self-Efficacy Scale [ASES]),
OA pain, stiffness, physical function (Western Ontario and McMaster Universities
Osteoarthritis Index [WOMAC]), and physical and mental health (Short Form 12-Item
health survey physical component and mental component summaries). Depression
status was assessed by blinded diagnostic interview (the Mini-International
Neuropsychiatric Interview) at intake and followup. RESULTS: Intent-to-treat
analyses indicated between-group superiority of iCBT over TAU on the primary
outcomes (PHQ-9: Hedges g = 1.01, 95% confidence interval [95% CI] 0.47, 1.54; K
10: Hedges g = 0.75, 95% CI 0.23, 1.28), at postintervention and 3-month followup
(PHQ-9: Hedges g = 0.90, 95% CI 0.36, 1.44; K-10: Hedges g = 0.94, 95% CI 0.41,
1.48), and on secondary OA-specific measures (ASES: Hedges g = -0.81, 95% CI
0.29, -1.33; WOMAC: Hedges g = 0.56-0.65, 95% CI 0.04, 1.18) at the 3-month
followup. The majority of iCBT participants (84%) no longer met diagnostic
criteria at 3-month followup. CONCLUSION: Results support the efficacy of an iCBT
program (requiring no face-to-face contact) for depression in individuals with
comorbid depression and OA of the knee. Importantly, the benefits of the program
extended beyond reduced depressive symptoms and distress to include increased
self-efficacy and improved pain, stiffness, and physical function at followup.
PMID- 28426918
TI - Advanced cancer caregiving as a risk for major depressive episodes and
generalized anxiety disorder.
AB - OBJECTIVE: Caregivers of advanced cancer patients provide extensive care
associated with high levels of caregiver distress. The degree to which cancer
caregiving increases caregivers' risk for a psychiatric disorder is unknown. The
current study examines whether advanced cancer caregiving poses distinct risks
for initial and recurrent major depressive episodes (MDEs) and generalized
anxiety disorder (GAD) relative to the general population. METHODS: Caregivers of
advanced cancer patients (N = 540) from Coping with Cancer were compared to
general population controls (N = 9282) from the National Comorbidity Survey
Replication. The general population comparison sample was propensity-weighted to
be demographically similar to the caregiver sample. RESULTS: Caregivers of
advanced cancer patients were more likely than individuals in the general
population to have an initial MDE (OR = 7.7; 95% CI, 3.5-17.0; P < .001), but no
more likely than the general population to have a recurrent MDE (OR = 1.1; 95%
CI, 0.6-2.1; P = .662). Caregivers were also more likely than the general
population to have GAD (OR = 3.0; 95% CI, 1.9-4.8; P < .001) and comorbid MDE and
GAD (OR = 2.5; 95% CI, 1.1-5.9; P = .038). CONCLUSIONS: The increased risk of
meeting diagnostic criteria for current MDE and GAD and comorbid MDE and GAD
associated with advanced cancer caregiving highlights the degree of emotional
burden among cancer caregivers. Clinical services that assess, prevent, and treat
depression and anxiety in cancer caregivers are needed to reduce the burden of
caregiving and improve the mental health of this growing population.
PMID- 28426919
TI - Unknown Intracardiac Electrogram.
AB - Watch a video presentation of this article. For additional educational resources,
please visit Medtronic Academy .
PMID- 28426920
TI - Dabigatran enhances platelet reactivity and platelet thrombin receptor expression
in patients with atrial fibrillation: comment.
PMID- 28426921
TI - The Marriage and Family Therapy Practice Research Network (MFT-PRN): Creating a
More Perfect Union Between Practice and Research.
AB - This article describes the Marriage and Family Therapy Practice Research Network
(MFT-PRN). The MFT-PRN is designed to build a professional community based on
practice-informed research and research-informed practice, increase the diversity
of participants in MFT research, and unify researchers and clinicians. Clinics
choose measures from a list that best represent their clinic needs. Clients'
outcomes are assessed regularly, and therapists receive immediate graphical
feedback on how clients are progressing or digressing. Data are pooled to create
a large and diverse database, while improving client outcomes. We will discuss
advantages of the MFT-PRN for researchers, therapists, clients, and agencies, and
provide one model that we hope will inform other collaborative clinical-research
models in the field of marriage and family therapy. Video Abstract is found in
the online version of the article.
PMID- 28426922
TI - Feasibility and acceptability of "healthy directions" a lifestyle intervention
for adults with lung cancer.
AB - OBJECTIVE: The aims of this feasibility study of an adapted lifestyle
intervention for adults with lung cancer were to (1) determine rates of
enrollment, attrition, and completion of 5 nurse-patient contacts; (2) examine
demographic characteristics of those more likely to enroll into the program; (3)
determine acceptability of the intervention; and (4) identify patient preferences
for the format of supplemental educational intervention materials. METHODS: This
study used a single-arm, pretest and posttest design. Feasibility was defined as
>=20% enrollment and a completion rate of 70% for 5 nurse-patient contact
sessions. Acceptability was defined as 80% of patients recommending the program
to others. Data was collected through electronic data bases and phone interviews.
Descriptive statistics, Fisher's exact test and Wilcoxon rank sum test were used
for analyses. RESULTS: Of 147 eligible patients, 42 (28.6%) enrolled and of
these, 32 (76.2%) started the intervention and 27 (N = 27/32; 84.4%; 95% CI,
67.2%-94.7%) completed the intervention. Patients who were younger were more
likely to enroll in the study (P = .04) whereas there were no significant
differences by gender (P = .35). Twenty-three of the 24 (95.8%) participants'
contacted posttest recommended the intervention for others. Nearly equal numbers
of participants chose the website (n = 16, 50%) vs print (n = 14, 44%).
CONCLUSION: The intervention was feasible and acceptable in patients with lung
cancer. Recruitment rates were higher and completion rates were similar as
compared to previous home-based lifestyle interventions for patients with other
types of cancer. Strategies to enhance recruitment of older adults are important
for future research.
PMID- 28426923
TI - Potassium-Promoted Molybdenum Carbide as a Highly Active and Selective Catalyst
for CO2 Conversion to CO.
AB - The high concentration of CO2 bound in seawater represents a significant
opportunity to extract and use this CO2 as a C1 feedstock for synthetic fuels.
Using an existing process, CO2 and H2 can be concurrently extracted from seawater
and then catalytically reacted to produce synthetic fuel. Hydrogenating CO2
directly into liquid hydrocarbons is exceptionally difficult, but by first
identifying a catalyst for selective CO production through the reverse water-gas
shift (RWGS) reaction, CO can then be hydrogenated to fuel through Fischer
Tropsch (FT) synthesis. Results of this study demonstrate that potassium-promoted
molybdenum carbide supported on gamma-Al2 O3 (K-Mo2 C/gamma-Al2 O3 ) is a low
cost, stable, and highly selective catalyst for RWGS over a wide range of
conversions. These findings are supported by X-ray diffraction, scanning electron
microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron
spectroscopy, and density functional theory calculations.
PMID- 28426924
TI - High-dose pulsed corticosteroid therapy combined with methotrexate for severe
alopecia areata of childhood.
PMID- 28426925
TI - Understanding the Role of Antibodies as Markers of Cancer-Associated Systemic
Sclerosis: Comment on the Article by Shah et al.
PMID- 28426926
TI - Sorbent material characterization using in-tube extraction needles as inverse gas
chromatography column.
AB - In-tube extraction is a full automated enrichment technique that consists of a
stainless-steel needle, packed with sorbent material for the extraction of
volatile and semivolatile compounds. In principle, all particulate sorbents used
for enrichment in air or headspace analysis can be used. However, the selection
of the sorbents is merely based on empirical considerations rather than on
experimental data, which is caused by a lack of knowledge about the relevant
physicochemical properties of the sorbent. Especially, the knowledge of
hydrostatic, advective, diffusive, and dispersion mechanisms in addition to
sorption enthalpies are important for combined transport and sorption models. To
provide these missing parameters, we developed and evaluated a method in which an
ordinary in-tube extraction needle was employed directly as column for sorbent
characterization by inverse gas chromatography. As probe compounds, benzene,
ethyl acetate, and 3-methyl-1-butanol were used to determine thermodynamic
parameters such as sorption enthalpy, partitioning constant between the solid and
gas phase, and kinetic parameters such as the diffusion coefficient, dispersion
coefficient, and apparent permeability, exemplarily. As sorbent, three
commercially available phases were characterized to demonstrate the applicability
of the method.
PMID- 28426927
TI - Severe, Drug-Resistant OCD Successfully Treated With rTMS and Concomitant
Multidisciplinary Psychotherapy: It's Not Only About the Coil.
PMID- 28426928
TI - Improvement of Escitalopram-Induced Sweating With Citalopram.
PMID- 28426929
TI - Exerting Enhanced Permeability and Retention Effect Driven Delivery by Ultrafine
Iron Oxide Nanoparticles with T1-T2 Switchable Magnetic Resonance Imaging
Contrast.
AB - Poor delivery efficiency remains a major challenge in nanomaterial-based tumor
targeted imaging and drug delivery. This work demonstrates a strategy to improve
nanoparticle delivery and intratumoral distribution using sub-5 nm (3.5 nm core
size) ultrafine iron oxide nanoparticles (uIONP) that can easily extravasate from
the tumor vasculature and readily diffuse into the tumor tissue compared to the
iron oxide nanoparticle (IONP) with larger sizes, followed by self-assembling in
the acidic tumor interstitial space to limit their re-entering into circulation.
By combining enhanced extravasation and reduced intravasation, we achieved
improved delivery and tumor retention of nanoparticles. Multiphoton imaging of
mice bearing orthotopic tumors co-injected with fluorescent dye-labeled
nanoparticles with different sizes showed that uIONPs exhibited more efficient
extravasation out of tumor vessels and penetrated deeper into the tumor than
larger sized IONP counterparts. Moreover, in vivo magnetic resonance imaging
revealed that uIONPs exhibited "bright" T1 contrast when dispersed in the tumor
vasculature and peripheral area at 1 h after intravenous administration, followed
by emerging "dark" T2 contrast in the tumor after 24 h. Observed T1-T2 contrast
switch indicated that uIONPs single-dispersed in blood with T1 contrast may self
assemble into larger clusters with T2 contrast after entering the tumor
interstitial space. Improved passive targeting and intratumoral delivery along
with increased tumor retention of uIONPs are due to both easy extravasation into
the tumor when single-dispersed and restricting intravasation back into
circulation after forming clusters, thus exerting the enhanced permeability and
retention effect for nanoparticle delivery to tumors.
PMID- 28426930
TI - Subcomponent Exchange Transforms an FeII4L4 Cage from High- to Low-Spin,
Switching Guest Release in a Two-Cage System.
AB - Subcomponent exchange transformed new high-spin FeII4L4 cage 1 into previously
reported low-spin FeII4L4 cage 2: 2-formyl-6-methylpyridine was ejected in favor
of the less sterically hindered 2-formylpyridine, with concomitant high- to low
spin transition of the cage's FeII centers. High-spin 1 also reacted more readily
with electron-rich anilines than 2, enabling the design of a system consisting of
two cages that could release their guests in response to combinations of
different stimuli. The addition of p-anisidine to a mixture of high-spin 1 and
previously-reported low-spin FeII4L6 cage 3 resulted in the destruction of 1 and
the release of its guest. However, initial addition of 2-formylpyridine to an
identical mixture of 1 and 3 resulted in the transformation of 1 into 2; added p
anisidine then reacted preferentially with 3 releasing its guest. The addition of
2-formylpyridine thus modulated the system's behavior, fundamentally altering its
response to the subsequent signal p-anisidine.
PMID- 28426931
TI - Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators
and Downregulators with Subtype-Specific ERalpha and ERbeta Activity.
AB - Estrogen receptor alpha (ERalpha) is an important target for the design of drugs
such as tamoxifen (2a) and fulvestrant (5). Three series of ER-ligands based on
the benzoxepin scaffold structure were synthesized: series I containing an
acrylic acid, series II with an acrylamide, and series III with a saturated
carboxylic acid substituent. These compounds were shown to be high affinity
ligands for the ER with nanomolar IC50 binding values. Series I acrylic acid
ligands were generally ERalpha selective. In particular, compound 13e featuring a
phenylpenta-2,4-dienoic acid substituent was shown to be antiproliferative and
downregulated ERalpha and ERbeta expression in MCF-7 breast cancer cells.
Interestingly, from series III, the phenoxybutyric acid derivative compound 22
was not antiproliferative and selectively downregulated ERbeta. A docking study
of the benzoxepin ligands was undertaken. Compound 13e is a promising lead for
development as a clinically relevant SERD, while compound 22 will be a useful
experimental probe for helping to elucidate the role of ERbeta in cancer cells.
PMID- 28426932
TI - Recycling Strategy for Fabricating Low-Cost and High-Performance Carbon Nanotube
TFT Devices.
AB - High-purity semiconducting single-walled carbon nanotubes (s-SWNTs) can be
obtained by conjugated polymer wrapping. However, further purification of sorted
s-SWNTs and high costs of raw materials are still challenges to practical
applications. It is inevitable that a lot of polymers still cover the surface of
s-SWNTs after separation, and the cost of the polymer is relatively higher than
that of SWNTs. Here, we demonstrated a facile isolated process to improve the
quality of s-SWNT solutions and films significantly. Compared with the untreated
s-SWNTs, the contact resistance between the s-SWNT and the electrode is reduced
by 20 times, and the thin-film transistors show 300% enhancement of current
density. In this process, most of the polymers can be recycled and reused
directly without any purification, which can greatly decrease the cost for s-SWNT
separation. The results presented herein demonstrate a new scalable and low-cost
approach for large-scale application of s-SWNTs in the electronics industry.
PMID- 28426933
TI - Triggering Assembly and Disassembly of a Supramolecular Cage.
AB - A novel supramolecular cage built from the self-assembly of tris(2
pyridylmethyl)amine zinc complexes through imine condensation chemistry is
reported. The cage recognition properties over a variety of structurally related
guests, together with the kinetic study of the template assembly and disassembly,
have been investigated in detail. This knowledge has been used to selectively
modulate the rate of both assembly and disassembly processes. In particular, a
novel disassembly method induced by strain release of the guest has been
developed.
PMID- 28426934
TI - From Permeation to Cluster Arrays: Graphene on Ir(111) Exposed to Carbon Vapor.
AB - Our scanning tunneling microscopy and X-ray photoelectron spectroscopy
experiments along with first-principles calculations uncover the rich
phenomenology and enable a coherent understanding of carbon vapor interaction
with graphene on Ir(111). At high temperatures, carbon vapor not only permeates
to the metal surface but also densifies the graphene cover. Thereby, in addition
to underlayer graphene growth, upon cool down also severe wrinkling of the
densified graphene cover is observed. In contrast, at low temperatures the
adsorbed carbon largely remains on top and self-organizes into a regular array of
fullerene-like, thermally highly stable clusters that are covalently bonded to
the underlying graphene sheet. Thus, a new type of predominantly sp2-hybridized
nanostructured and ultrathin carbon material emerges, which may be useful to
encage or stably bind metal in finely dispersed form.
PMID- 28426935
TI - Manipulation of Mg2+-Ca2+ Switch on the Development of Bone Mimetic
Hydroxyapatite.
AB - Ionic substitution can affect essential physicochemical properties leading to a
specific biological behavior upon implantation. Therefore, it has been proposed
as a tool to increase the biological efficiency of calcium phosphate based
materials. In the following study, we have evaluated the contribution of an
important cation in nature, Mg2+, into the structure of previously studied
biocompatible and biodegradable hydroxyapatite (HA) nanorods and its subsequent
effect on its chemical, morphology, and bone mimetic articulation. Mg2+
substituted HA samples were synthesized by an aqueous wet-chemical precipitation
method, followed by an hydrothermal treatment involving a Mg2+ precursor that
partially replace Ca2+ ions into HA crystal lattice; Mg2+ concentrations were
modulated to obtain a nominal composition similar to that exists in calcified
tissues. Hydrothermally synthesized Mg2+-substituted HA nanoparticles were
characterized by X-ray powder diffraction, FT-NIR and EDX spectroscopies, field
emission scanning and high resolution transmission electron microscopies (FE-SEM,
H-TEM). Molecular modeling combining ab initio methods and power diffraction data
were also performed. Results showed that Mg2+-substitution promoted the formation
of calcium deficient HA (cdHA) where Mg2+ replacement is energetically favored at
Ca(1) position in a limited and specific amount directing the additional Mg2+
toward the surface of the crystal. The control of Mg2+ incorporation into HA
nanorods gave rise to a tailored crystallinity degree, cell parameters,
morphology, surface hydration, solubility, and degradation properties in a dose
replacement dependent manner. The obtained materials show qualities that
conjugated together to drive an optimal in vitro cellular viability, spreading,
and proliferation confirming their biocompatibility. In addition, an improved
adhesion of osteoblast was evidenced after Mg2+-Ca2+ substitution.
PMID- 28426936
TI - Cholesterol-Assisted Bacterial Cell Surface Engineering for Photodynamic
Inactivation of Gram-Positive and Gram-Negative Bacteria.
AB - Antibacterial photodynamic therapy (PDT), which enables effective killing of
regular and multidrug-resistant (MDR) bacteria, is a promising treatment modality
for bacterial infection. However, because most photosensitizer (PS) molecules
fail to strongly interact with the surface of Gram-negative bacteria, this
technique is suitable for treating only Gram-positive bacterial infection, which
largely hampers its practical applications. Herein, we reveal for the first time
that cholesterol could significantly facilitate the hydrophobic binding of PSs to
the bacterial surface, achieving the hydrophobic interaction-based bacterial cell
surface engineering that could effectively photoinactivate both Gram-negative and
Gram-positive bacteria. An amphiphilic polymer composed of a polyethylene glycol
(PEG) segment terminated with protoporphyrin IX (PpIX, an anionic PS) and
cholesterol was constructed (abbreviated Chol-PEG-PpIX), which could self
assemble into micelle-like nanoparticles (NPs) in aqueous solution. When
encountering the Gram-negative Escherichia coli cells, the Chol-PEG-PpIX NPs
would disassemble and the PpIX moieties could effectively bind to the bacterial
surface with the help of the cholesterol moieties, resulting in the significantly
enhanced fluorescence emission of the bacterial surface. Under white light
irradiation, the light-triggered singlet oxygen (1O2) generation of the membrane
bound PpIX could not only severely damage the outer membrane but also facilitate
the entry of external Chol-PEG-PpIX into the bacteria, achieving >99.99%
bactericidal efficiency. Besides, as expected, the Chol-PEG-PpIX NPs also
exhibited excellent antibacterial performance against the Gram-positive
Staphylococcus aureus. We also verified that this nanoagent possesses negligible
dark cytotoxicity toward mammalian cells and good hemocompatibility. To the best
of our knowledge, this study demonstrates for the first time the feasibility of
constructing a fully hydrophobic interaction-based and outer membrane-anchored
antibacterial PDT nanoagent.
PMID- 28426937
TI - High-Throughput Quantitative Intrinsic Thiol Reactivity Evaluation Using a
Fluorescence-Based Competitive Endpoint Assay.
AB - In a high-throughput screening (HTS) process, the chemical reactivity of test
samples should be carefully examined because such reactive compounds may lead to
false-positive results and adverse effects in vivo. Among all natural amino
acids, the thiol side chain in cysteine has the highest nucleophilicity; thus,
assessment of intrinsic thiol group reactivity in the HTS processes is expected
to accelerate drug discovery. In general, kchem (M-1s-1), the secondary reaction
rate constant of a compound to thiol, can be evaluated via time course
measurements of thiol-compound adducts using liquid chromatography-mass
spectroscopy; this requires time-consuming and labor-intensive procedures. To
overcome this issue, we developed a fluorescence-based competitive endpoint assay
that allows quantitative calculation of the reaction rate of test compounds in an
HTS format. Our assay is based on the competitive reaction for a free thiol
(e.g., glutathione) between the test compounds and a fluorescent probe, o
maleimide BODIPY. Our assay provides robust data with a satisfactory throughput
at an affordable cost. Our kchem evaluation method has advantages over previous
assays in terms of higher throughput and quantitativeness. Thus, it contributes
to early elimination of reactive compounds as well as quantitative evaluation of
the kchem values of covalent inhibitors.
PMID- 28426938
TI - High-Throughput Screening to Identify Inhibitors of DEAD Box Helicase DDX41.
AB - The human DEAD (Asp-Glu-Ala-Asp) box protein DDX41, a member of the DEXDc
helicase family, has nucleic acid-dependent ATPase and RNA and DNA translocase
and unwinding activities. DDX41 is affected by somatic mutations in sporadic
cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients
with germline DDX41 mutations. The R525H mutation in DDX41 is thought to play
important roles in the development of hereditary myelodysplastic syndrome and
acute myelocytic leukemia. In this study, human DDX41 and its R525H mutant
(R525H) were expressed in Escherichia coli and purified. The ATPase activities of
the recombinant DDX41 and R525H proteins were dependent on both ATP and double
stranded DNA (dsDNA), such as poly(dG-dC) and poly(dA-dT). High-throughput
screening was performed with a dsDNA-dependent ATPase assay using the human R525H
proteins. After hit confirmation and counterscreening, several small-molecule
inhibitors were successfully identified. These compounds show DDX41-selective
inhibitory activities.
PMID- 28426939
TI - High-Throughput Agonist Shift Assay Development for the Analysis of M1-Positive
Allosteric Modulators.
AB - Agonist shift assays feature cross-titrations of allosteric modulators and
orthosteric ligands. Information generated in agonist shift assays can include a
modulator's effect on the orthosteric agonist's potency (alpha) and efficacy
(beta), as well as direct agonist activity of the allosteric ligand (tauB) and
the intrinsic binding affinity of the modulator to the unoccupied receptor (KB).
Because of the heavy resource demand and complex data handling, these allosteric
parameters are determined infrequently during the course of a drug discovery
program and on a relatively small subset of compounds. Automation of agonist
shift assays enables this data-rich analysis to evaluate a larger number of
compounds, offering the potential to differentiate compound classes earlier and
prospectively prioritize based on desired molecular pharmacology. A high
throughput calcium-imaging agonist shift assay was pursued to determine the
allosteric parameters of over 1000 positive allosteric modulator (PAM) molecules
for the human muscarinic acetylcholine receptor 1 (M1). Control compounds were
run repeatedly to demonstrate internal consistency. Comparisons between potency
measurements and the allosteric parameter results demonstrate that these
different types of measurements do not necessarily correlate, highlighting the
importance of fully characterizing and understanding the allosteric properties of
leads.
PMID- 28426940
TI - Prospective Assessment of Virtual Screening Heuristics Derived Using a Novel
Fusion Score.
AB - High-throughput screening (HTS) is a widespread method in early drug discovery
for identifying promising chemical matter that modulates a target or phenotype of
interest. Because HTS campaigns involve screening millions of compounds, it is
often desirable to initiate screening with a subset of the full collection.
Subsequently, virtual screening methods prioritize likely active compounds in the
remaining collection in an iterative process. With this approach, orthogonal
virtual screening methods are often applied, necessitating the prioritization of
hits from different approaches. Here, we introduce a novel method of fusing these
prioritizations and benchmark it prospectively on 17 screening campaigns using
virtual screening methods in three descriptor spaces. We found that the fusion
approach retrieves 15% to 65% more active chemical series than any single machine
learning method and that appropriately weighting contributions of similarity and
machine-learning scoring techniques can increase enrichment by 1% to 19%. We also
use fusion scoring to evaluate the tradeoff between screening more chemical
matter initially in lieu of replicate samples to prevent false-positives and find
that the former option leads to the retrieval of more active chemical series.
These results represent guidelines that can increase the rate of identification
of promising active compounds in future iterative screens.
PMID- 28426941
TI - Behavioral deficits and neural damage of Caenorhabditis elegans induced by three
rare earth elements.
AB - Rare earth elements (REEs) are widely used in industry, agriculture, medicine and
daily life in recent years. However, environmental and health risks of REEs are
still poorly understood. In this study, neurotoxicity of trichloride neodymium,
praseodymium and scandium were evaluated using nematode Caenorhabditis elegans as
the assay system. Median lethal concentrations (48 h) were 99.9, 157.2 and 106.4
mg/L for NdCl3, PrCl3 and ScCl3, respectively. Sublethal dose (10-30 mg/L) of
these trichloride salts significantly inhibited body length of nematodes. Three
REEs resulted in significant declines in locomotor frequency of body bending,
head thrashing and pharyngeal pumping. In addition, mean speed and wavelength of
crawling movement were significantly reduced after chronic exposure. Using
transgenic nematodes, we found NdCl3, PrCl3 and ScCl3 resulted in loss of
dendrite and soma of neurons, and induced down-expression of dat-1::GFP and unc
47::GFP. It indicates that REEs can lead to damage of dopaminergic and GABAergic
neurons. Our data suggest that exposure to REEs may cause neurotoxicity of
inducing behavioral deficits and neural damage. These findings provide useful
information for understanding health risk of REE materials.
PMID- 28426943
TI - How strong is the evidence for using blood biomarkers alone to screen for alcohol
consumption during pregnancy? A systematic review.
AB - Accurate and early identification of women at risk from alcohol consumption
during pregnancy allows education and support programmes to be targeted at those
most in need. We aimed to conduct a systematic review to compare the efficacy of
blood analysis and maternal self-report in detecting at risk women during
pregnancy. This review investigated diagnostic accuracy. We searched four
databases (Medline, Embase, Psychinfo and CINAHL) for relevant articles and
conducted hand searches of recent issues of key journals in the field. No
restriction was placed on inclusion in terms of publication date or language.
Studies were deemed eligible if they were original research and included a direct
comparison of the results of blood biomarker analysis and self-reported alcohol
use for the detection of alcohol consumption in pregnant women. Quality appraisal
of included studies was conducted using the QUADAS II tool. Eight studies met the
inclusion criteria. Gamma-glutamyltransferase (GGT) was investigated in five
studies, mean corpuscular volume (MCV) and phosphatidylethanol (PEth) in three
studies and carbohydrate deficient transferrin (CDT), aspartate aminotransferase
(AST), alanine aminotransferase (ALT) and whole blood associated acetaldehyde
assay (WBAA) were each investigated in two studies. Although all of the studies
were rated of good methodological quality, none of the biomarkers had both high
sensitivity and specificity when compared to self-report. There was some evidence
that a combination of biomarkers, or combining biomarkers with self-report,
increases accuracy. In summary, the blood biomarkers examined were of limited use
in screening for low and moderate alcohol consumption in pregnancy when compared
to self-report. However, certain biomarkers, such and CDT and PEth may complement
self-report and help improve the accuracy of diagnosis.
PMID- 28426942
TI - Polychlorinated biphenyl and polybrominated diphenyl ether profiles in serum from
cattle, sheep, and goats across California.
AB - It has been previously been shown by our lab and others that persistent organic
pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl
ethers (PBDEs), are contaminants in milk produced for human consumption. To
further this research we determined the concentration of 21 PCB and 14 PBDE
congeners in livestock serum, mainly bovine, across California. Congeners were
extracted from serum using solid phase extraction (SPE), cleaned up by silica
cartridge and quantified using gas chromatography-triple quadruple mass
spectrometry. We detected significant differences among species and the
production class of cattle (beef or dairy). The sum of all 21 PCB congeners
(SigmaPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL,
respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum
of all 14 PBDE congeners (SigmaPBDEs) in caprine and ovine sera was 2.82 and 2.39
ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean SigmaPCBs in
dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean
SigmaPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle.
There were no regional differences in the SigmaPCBs or SigmaPBDEs in cattle
distributed across California. These results highlight the fact that livestock
are still being exposed to these pollutants yet little is known about where this
exposure may be coming from.
PMID- 28426944
TI - A comparison between reduced-port robotic surgery and multiport robot-assisted
laparoscopy for myomectomy.
AB - OBJECTIVE: To compare the surgical outcomes between reduced-port robotic surgery
(RPRS) using the Octo-Port channel and multiport robot-assisted laparoscopy for
myomectomy. STUDY DESIGN: This prospective study compared and analyzed data from
15 consecutive women who underwent RPRS for myomectomy and 15 consecutive women
who underwent multiport robot-assisted laparoscopy to treat symptomatic uterine
myoma from January 2016 to June 2016. The patients were treated by two surgeons
at two institutions. RESULTS: The two study groups did not differ
demographically. The differences in surgical outcomes, such as docking time,
console time, hospital stay, estimated blood loss, Hb change, myoma count, and
weight, also did not differ between the two groups. On the contrary, the number
of port site was only 2 in RPRS compared with 4-5 in multiport robot-assisted
laparoscopic myomectomy. CONCLUSION: RPRS for myomectomy seems technically
feasible and safe, with short-term perioperative outcomes similar to those from
multiport robot-assisted laparoscopic myomectomy.
PMID- 28426945
TI - Testosterone levels in healthy men correlate negatively with serotonin 4 receptor
binding.
AB - The serotonergic system integrates sex steroid information and plays a central
role in mood and stress regulation, cognition, appetite and sleep. This interplay
may be critical for likelihood of developing depressive episodes, at least in a
subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes
central serotonergic tonus, which may be related to endogenous sex-steroid levels
in the mentally healthy state even though this remains elusive. Here we evaluate
if peripheral levels of estradiol and testosterone are associated with 5-HT4R
binding as imaged by [11C]SB207145 positron emission tomography in a group of 41
healthy men. We estimated global 5-HT4R binding using a latent variable model
framework, which models shared correlation between 5-HT4R across multiple brain
regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus,
pallidostriatum and neocortex). We tested whether testosterone and estradiol
predict global 5-HT4R, adjusting for age. We found that testosterone, but not
estradiol, correlated negatively with global 5-HT4R levels (p=0.02) suggesting
that men with high levels of testosterone have higher cerebral serotonergic
tonus. Our findings corroborate the link between sex hormone levels and serotonin
signalling. Future longitudinal studies in clinical relevant populations are
needed to elucidate the potential importance of testosterone in the
pathophysiology of e.g. major depression and its treatment.
PMID- 28426946
TI - Quantification of rubidium as a trace element in beef using laser induced
breakdown spectroscopy.
AB - This study evaluates the potential of laser induced breakdown spectroscopy (LIBS)
coupled with chemometrics to develop a quantification model for rubidium (Rb) in
minced beef. A LIBSCAN 150 system was used to collect LIBS spectra of minced beef
samples. Beef liver was used to spike the Rb levels in minced beef. All samples
were dried, powdered and pelleted using a hydraulic press. Measurements were
conducted by scanning 100 different locations with an automated XYZ sample
chamber. Partial least squares regression (PLSR) was used to develop the
calibration model, yielding a calibration coefficient of determination (Rc2) of
0.99 and a root mean square error of calibration (RMSEC) of 0.05ppm. The model
also showed good results with leave-one-out cross validation, yielding a cross
validation coefficient of determination (Rcv2) of 0.90 and a root mean square
error of cross-validation (RMSECV) of 0.22ppm. The current study shows the
potential of LIBS as a rapid analysis tool for the meat processing industry.
PMID- 28426947
TI - Structural neuroplasticity of the superior temporal plane in early and late
blindness.
AB - Blindness is associated with well-documented changes to the morphometry and
function of the occipital cortex. By comparison, its impact on the perisylvian
regions in the superior temporal plane (STP) is poorly understood, with many
studies reporting null findings on this issue. Here we re-approach this question
using a morphometric analysis that relied on fine-scale, manual annotation of 13
sub-regions within the STP and that quantified both univariate and multivariate
differences in morphometry. We applied these analyses to both cortical thickness
(CT) and surface area (SA) data from congenitally and late blind, as compared to
two matched sighted control groups. The univariate analyses indicated that for
CT, no region differentiated blind from sighted, and for SA, two regions showed
lower values for congenitally blind. Moreover, the multivariate analyses
identified more robust signatures of plasticity in blindness. Specifically,
pairwise regional correlations of CT values between contralateral regions were
significantly higher for both blind groups as compared to sighted controls. A
similar pattern for SA data was found for congenitally blind alone. Our findings
indicate that blindness strongly impacts STP, resulting in a more coordinated
pattern of interhemispheric morphometric development. We discuss implications for
theories of language plasticity and models of neuroplasticity in the blind.
PMID- 28426948
TI - Digit ratio (2D:4D) and handgrip strength are correlated in women (but not in
men) in Hui ethnicity.
AB - INTRODUCTION: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is
used as a biomarker of prenatal testosterone exposure and was found associated
with physical ability, such as handgrip strength (HGS). Recently, this
association has been discussed in several ethnic groups. AIMS: To investigate
correlations between 2D:4D and HGS in Chinese population of Ningxia Hui
ethnicity. METHODS: Here we firstly present the evidence on digit ratio and HGS
of 346 college students (119 males and 227 females) by collecting photographs and
HGS of both hands at Yinchuan city, in the Ningxia province of China. RESULTS:
Females have higher mean values of digit ratio than males; significant variances
of 3D:5D (left and right: P<0.05), 2D:3D, 3D:4D (left and right: P<0.01) and
2D:4D, 2D:5D (left and right: P<0.001) were found between different sex. Males
showed significantly greater HGS than females on both hands. 2D:4D of both hands
were significantly negative correlated with HGS in females (but not in males).
CONCLUSIONS: 2D:4D ratio is negatively correlated with HGS in a Chinese
population (especially in females) of Ningxia Hui ethnicity.
PMID- 28426949
TI - Agarra, agarran: Evidence of early comprehension of subject-verb agreement in
Spanish.
AB - Studies across many languages (e.g., Dutch, English, Farsi, Spanish, Xhosa) have
failed to show early acquisition of subject-verb (SV) agreement, whereas recent
studies on French reveal acquisition by 30months of age. Using a similar
procedure as in previous French studies, the current study evaluated whether
earlier comprehension of SV agreement in (Mexican) Spanish can be revealed when
task demands are lowered. Two experiments using a touch-screen pointing task
tested comprehension of SV agreement by monolingual Spanish-speaking children
growing up in Mexico City between about 3 and 5years of age. In Experiment 1, the
auditory stimuli consisted of a transitive verb+pseudonoun object (e.g., agarra
el micho 'he throws the micho' vs. agarran el duco 'they throw the duco');
results failed to show early comprehension of SV agreement, replicating previous
findings. In Experiment 2, the same stimuli were used, with the crucial
difference that the word objeto 'object' replaced all pseudonouns; results
revealed SV agreement comprehension as early as 41 to 50months. Taken together,
our findings show that comprehension at this age is facilitated when task demands
are lowered, here by not requiring children to process pseudowords (even when
these were not critical to the task). Hence, these findings underscore the
importance of task-specific/stimulus-specific features when testing early
morphosyntactic development and suggest that previous results may have
underestimated Spanish-speaking children's competence.
PMID- 28426950
TI - Testing the validity of a continuous false belief task in 3- to 7-year-old
children.
AB - In two studies, we examined young children's performance on the paper-and-pencil
version of the Sandbox task, a continuous measure of false belief, and its
relations with other false belief and inhibition tasks. In Study 1, 96 children
aged 3 to 7years completed three false belief tasks (Sandbox, Unexpected
Contents, and Appearance/Reality) and two inhibition tasks (Head-Shoulders-Knees
Toes and Grass/Snow). Results revealed that false belief bias-a measure of
egocentrism-on the Sandbox task correlated with age but not with the Unexpected
Contents or Appearance/Reality task or with measures of inhibition after
controlling for age. In Study 2, 90 3- to 7-year-olds completed five false belief
tasks (Sandbox, Unexpected Contents, Appearance/Reality, Change of Location, and
a second-order false belief task), two inhibition tasks (Simon Says and
Grass/Snow), and a receptive vocabulary task (Peabody Picture Vocabulary Test).
Results showed that false belief bias on the Sandbox task correlated negatively
with age and with the Change of Location task but not with the other false belief
or inhibition tasks after controlling for age and receptive vocabulary. The
Sandbox task shows promise as an age-sensitive measure of false belief
performance during early childhood and shows convergent and discriminant
validity.
PMID- 28426951
TI - Temperature induced self-assembly of amino acid-derived vinyl block copolymers
via dual phase transitions.
AB - The unique thermoresponsive phase behaviors of diblock copolymers from amino acid
derived vinyl monomers have been demonstrated in view of variation in the
aggregation state in water. Amino acid-based block copolymers composed of N
acryloyl-Ala-methylester (NAAMe) and N-acryloyl-betaAla-methylester (NAbetaAMe)
are successfully synthesized by RAFT polymerization. The resultant block
copolymers poly(NAAMe48-b-NAbetaAMem) contain a constant degree of polymerization
(DP=48) of the poly(NAAMe) block, but the DP of the poly(NAbetaAMe) block varies
(m=80-122). The turbidimetry subjected to these copolymer aqueous solutions
exhibits two LCST transitions upon heating. In the 1st LCST region, the block
copolymer forms a relatively loose-molecular packing, while large aggregates due
to partial dehydration of polymer molecules, which subsequently transform into a
stable micelle structure in a region of 30-39 degrees C. Finally, a tight
aggregate composed of the dehydrated micelles is formed. Temperature-dependent 1H
NMR spectroscopy of the diblock copolymers also supports such a postulation for
the dual phase transitions and stable micelle structure formation. In addition, a
typical salting-out effect is observed in the thermal behavior of the polymer,
but a serious cytotoxic effect is not observed in NIH/3T3 cells, suggesting that
the novel diblock copolymers are relevant for biomedical applications.
PMID- 28426952
TI - Plant viruses and bacteriophages for drug delivery in medicine and biotechnology.
AB - There are a wide variety of synthetic and naturally occurring nanomaterials under
development for nanoscale cargo-delivery applications. Viruses play a special
role in these developments, because they can be regarded as naturally occurring
nanomaterials evolved to package and deliver cargos. While any nanomaterial has
its advantage and disadvantages, viral nanoparticles (VNPs), in particular the
ones derived from plant viruses and bacteriophages, are attractive options for
cargo-delivery as they are biocompatible, biodegradable, and non-infectious to
mammals. Their protein-based structures are often understood at atomic resolution
and are amenable to modification with atomic-level precision through chemical and
genetic engineering. Here we present a focused review of the emerging technology
development of plant viruses and bacteriophages targeting human health and
agricultural applications. Key target areas of development are their use in
chemotherapy, photodynamic therapy, pesticide-delivery, gene therapy, vaccine
carriers, and immunotherapy.
PMID- 28426953
TI - MethyLock: DNA Demethylation Is the Epigenetic Key to Axon Regeneration.
AB - In this issue of Neuron, Weng et al. (2017) reveal a role for active DNA
demethylation in allowing axon regeneration to occur in the mature nervous system
following axonal injury.
PMID- 28426954
TI - Neuronal Polarity: MAP2 Shifts Secretory Vesicles into High Gear for Long-Haul
Transport down the Axon.
AB - Accurate control of polarized cargo trafficking is essential for neuronal
function. In this issue of Neuron, Gumy et al. (2017) show that MAP2 defines a
pre-axonal filtering zone and controls axonal cargo transport by influencing the
activities of distinct kinesin motors.
PMID- 28426955
TI - The Small World of a Fear Memory.
AB - How are fear memories organized? In this issue of Neuron, Vetere et al. (2017)
take a network-based approach to demonstrate the importance of highly
interconnected hub regions in the consolidation of a fear memory. By doing so,
they provide an elegant framework for predicting behavior from functional network
properties.
PMID- 28426956
TI - Amines, Astrocytes, and Arousal.
AB - Amine neurotransmitters, such as noradrenaline, mediate arousal, attention, and
reward in the CNS. New data suggest that, from flies to mammals, a major
mechanism for amine transmitter action is to raise astrocyte [Ca2+]i and release
gliotransmitters that modulate neuronal activity and behavior.
PMID- 28426957
TI - Emerging Global Initiatives in Neurogenetics: The Enhancing Neuroimaging Genetics
through Meta-analysis (ENIGMA) Consortium.
AB - The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium is
a global team science effort, now including over 800 scientists spread across 340
institutions in 35 countries, with the shared goal of understanding disease and
genetic influences on the brain. This "crowdsourcing" approach to team
neuroscience has unprecedented power for advancing our understanding of both
typical and atypical human brain development.
PMID- 28426958
TI - Elucidating the Role of TREM2 in Alzheimer's Disease.
AB - Alzheimer's disease (AD) is the sixth leading cause of death in the United States
and the most common cause of dementia in the elderly. Genetic factors, such as
rare variants in the microglial-expressed gene TREM2, strongly impact the
lifetime risk of developing AD. Several recent studies have described dramatic
TREM2-dependent phenotypes in mouse models of amyloidosis that point to an
important role for TREM2 in regulating the response of the innate immune system
to Abeta pathology. Furthermore, elevations in the CSF levels of soluble TREM2
fragments implicate changes in inflammatory pathways as occurring coincident with
markers of neuronal damage and the onset of clinical dementia in AD. Here, we
review the rapidly developing literature surrounding TREM2 in AD that may provide
novel insight into the broader role of the innate immune system in
neurodegenerative disease.
PMID- 28426959
TI - Ontogenesis of Lateralization.
AB - The brains of humans and other animals are asymmetrically organized, but we still
know little about the ontogenetic and neural fundaments of lateralizations. Here,
we review the current state of understanding about the role of genetic and non
genetic factors for the development of neural and behavioral asymmetries in
vertebrates. At the genetic level, the Nodal signaling cascade is of central
importance, but several other genetic pathways have been discovered to also shape
the lateralized embryonic brain. Studies in humans identified several relevant
genes with mostly small effect sizes but also highlight the extreme importance of
non-genetic factors for asymmetry development. This is also visible in visual
asymmetry in birds, in which genes only affect embryonic body position, while the
resulting left-right difference of visual stimulation shapes visual pathways in a
lateralized way. These and further studies in zebrafish and humans highlight that
the many routes from genes to asymmetries of function run through left-right
differences of neural pathways. They constitute the lateralized blueprints of our
perception, cognition, and action.
PMID- 28426960
TI - Editorial Note to: Endogenous Piezo1 Can Confound Mechanically Activated Channel
Identification and Characterization.
PMID- 28426961
TI - Endogenous Piezo1 Can Confound Mechanically Activated Channel Identification and
Characterization.
AB - A gold standard for characterizing mechanically activated (MA) currents is via
heterologous expression of candidate channels in naive cells. Two recent studies
described MA channels using this paradigm. TMEM150c was proposed to be a
component of an MA channel partly based on a heterologous expression approach
(Hong et al., 2016). In another study, Piezo1's N-terminal "propeller" domain was
proposed to constitute an intrinsic mechanosensitive module based on expression
of a chimera between a pore-forming domain of the mechanically insensitive ASIC1
channel and Piezo1 (Zhao et al., 2016). When we attempted to replicate these
results, we found each construct conferred modest MA currents in a small fraction
of naive HEK cells similar to the published work. Strikingly, these MA currents
were not detected in cells in which endogenous Piezo1 was CRISPR/Cas9
inactivated. These results highlight the importance of choosing cells lacking
endogenous MA channels to assay the mechanotransduction properties of various
proteins. This Matters Arising paper is in response to Hong et al. (2016) and
Zhao et al. (2016) in Neuron. See also the response papers by Hong et al. (2017)
and Zhao et al. (2017) published concurrently with this Matters Arising.
PMID- 28426962
TI - Evidence for Mechanosensitive Channel Activity of Tentonin 3/TMEM150C.
AB - Mechanosensation is essential for various physiological processes, and it is
mediated by mechanotransduction channels. Recently, we reported that
TMEM150C/Tentonin 3 (TTN3) confers mechanically activated currents with slow
inactivation kinetics in several cell types, including dorsal root ganglion
neurons (Hong et al., 2016). The accompanying Matters Arising by Dubin, Murthy,
and colleagues confirms that naive heterologous cells demonstrate a mechanically
activated current, but finds that this response is absent in CRISPR-Cas9 Piezo1
knockout cell lines and suggests that TTN3 is a modulator of Piezo1. We present
and discuss evidence based on co-expression of TTN3 and Peizo1 and mutant
variants of the pore region of TTN3 to support that TTN3 is a pore-forming unit,
not an amplifying adaptor for Piezo1 activity. This Matters Arising Response
paper, along with Zhao et al. (2017), addresses the Matters Arising from Dubin et
al. (2017), published concurrently in this issue of Neuron.
PMID- 28426963
TI - Heterologous Expression of the Piezo1-ASIC1 Chimera Induces Mechanosensitive
Currents with Properties Distinct from Piezo1.
AB - Piezo1 represents a prototype of the mammalian mechanosensitive cation channel,
but its molecular mechanism remains elusive. In a recent study, we showed that C
terminal region, which contains the last two TMs, of 2189-2547 of Piezo1 forms
the bona fide pore module, and systematically identified the pore-lining helix
and key pore-property-determining residues (Zhao et al., 2016). Furthermore, we
have engineered the Piezo1(1-2190)-ASIC1 chimera (fusing the N-terminal region of
1-2190 to the mechano-insensitive ASIC1) that mediated mechanical- and acid
evoked currents in HEK293T cells, indicating the sufficiency of the N-terminal
region in mechanotransduction. Now in a Matters Arising, the authors specifically
questioned the implication of the chimera data among the many findings shown in
our paper. They replicated the chimera-mediated mechanosensitive currents in
HEK293T cells that have nearly no detectable expression of endogenous Piezo1, but
paradoxically found the chimera to be less effective in Piezo1 knockout HEK293T
cells, indicating the involvement of endogenous Piezo1. In this Matters Arising
Response, we discuss the chimera results and consider potential interpretations
in light of the Matters Arising from Dubin et al. (2017), published concurrently
in this issue of Neuron. Please see also the response from Hong et al. (2017),
published in this issue.
PMID- 28426964
TI - iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
AB - Microglia play critical roles in brain development, homeostasis, and neurological
disorders. Here, we report that human microglial-like cells (iMGLs) can be
differentiated from iPSCs to study their function in neurological diseases, like
Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to
microglia in vivo, and whole-transcriptome analysis demonstrates that they are
highly similar to cultured adult and fetal human microglia. Functional assessment
of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli,
migrate and undergo calcium transients, and robustly phagocytose CNS substrates.
iMGLs were used to examine the effects of Abeta fibrils and brain-derived tau
oligomers on AD-related gene expression and to interrogate mechanisms involved in
synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human
brain organoids resemble microglia in vivo. Together, these findings demonstrate
that iMGLs can be used to study microglial function, providing important new
insight into human neurological disease.
PMID- 28426965
TI - Formation and Maintenance of Functional Spines in the Absence of Presynaptic
Glutamate Release.
AB - Dendritic spines are the major transmitter reception compartments of
glutamatergic synapses in most principal neurons of the mammalian brain and play
a key role in the function of nerve cell circuits. The formation of functional
spine synapses is thought to be critically dependent on presynaptic glutamatergic
signaling. By analyzing CA1 pyramidal neurons in mutant hippocampal slice
cultures that are essentially devoid of presynaptic transmitter release, we
demonstrate that the formation and maintenance of dendrites and functional spines
are independent of synaptic glutamate release.
PMID- 28426966
TI - Assembly of Excitatory Synapses in the Absence of Glutamatergic
Neurotransmission.
AB - Synaptic excitation mediates a broad spectrum of structural changes in neural
circuits across the brain. Here, we examine the morphologies, wiring, and
architectures of single synapses of projection neurons in the murine hippocampus
that developed in virtually complete absence of vesicular glutamate release.
While these neurons had smaller dendritic trees and/or formed fewer contacts in
specific hippocampal subfields, their stereotyped connectivity was largely
preserved. Furthermore, loss of release did not disrupt the morphogenesis of
presynaptic terminals and dendritic spines, suggesting that glutamatergic
neurotransmission is unnecessary for synapse assembly and maintenance. These
results underscore the instructive role of intrinsic mechanisms in synapse
formation.
PMID- 28426968
TI - MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent
Cargo Transport in Sensory Neurons.
AB - Polarized cargo transport is essential for neuronal function. However, the
minimal basic components required for selective cargo sorting and distribution in
neurons remain elusive. We found that in sensory neurons the axon initial segment
is largely absent and that microtubule-associated protein 2 (MAP2) defines the
cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry
by coordinating the activities of molecular motors. We show that distinct
kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal
cargo trafficking, while kinesin-1 slows down axonal cargo transport. MAP2
inhibits "slow" kinesin-1 motor activity and allows kinesin-3 to drive robust
cargo transport from the soma into the axon. In the distal axon, the inhibitory
action of MAP2 decreases, leading to regained kinesin-1 activity and vesicle
distribution. We propose that selective axonal cargo trafficking requires the
MAP2-defined pre-axonal filtering zone and the ability of cargos to switch
between distinct kinesin motor activities.
PMID- 28426969
TI - Chemogenetic Interrogation of a Brain-wide Fear Memory Network in Mice.
AB - Behavior depends on coordinated activity across multiple brain regions. Within
such networks, highly connected hub regions are assumed to disproportionately
influence behavioral output, although this hypothesis has not been systematically
evaluated. Previously, by mapping brain-wide expression of the activity-regulated
gene c-fos, we identified a network of brain regions co-activated by fear memory.
To test the hypothesis that hub regions are more important for network function,
here, we simulated node deletion in silico in this behaviorally defined
functional network. Removal of high degree nodes produced the greatest network
disruption (e.g., reduction in global efficiency). To test these predictions in
vivo, we examined the impact of post-training chemogenetic silencing of different
network nodes on fear memory consolidation. In a series of independent
experiments encompassing 25% of network nodes (i.e., 21/84 brain regions), we
found that node degree accurately predicted observed deficits in memory
consolidation, with silencing of highly connected hubs producing the largest
impairments.
PMID- 28426967
TI - An Intrinsic Epigenetic Barrier for Functional Axon Regeneration.
AB - Mature neurons in the adult peripheral nervous system can effectively switch from
a dormant state with little axonal growth to robust axon regeneration upon
injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal
growth competence are not well understood. Here, we show that peripheral sciatic
nerve lesion in adult mice leads to elevated levels of Tet3 and 5
hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3
is required for robust axon regeneration of DRG neurons and behavioral recovery.
Mechanistically, peripheral nerve injury induces DNA demethylation and
upregulation of multiple regeneration-associated genes in a Tet3- and thymine DNA
glycosylase-dependent fashion in DRG neurons. In addition, Pten deletion-induced
axon regeneration of retinal ganglion neurons in the adult CNS is attenuated upon
Tet1 knockdown. Together, our study suggests an epigenetic barrier that can be
removed by active DNA demethylation to permit axon regeneration in the adult
mammalian nervous system.
PMID- 28426970
TI - Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission.
AB - The paraventricular nucleus of the thalamus (PVT) is thought to regulate
behavioral responses under emotionally arousing conditions. Reward-associated
cues activate PVT neurons; however, the specific PVT efferents regulating reward
seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT
activity under two emotionally distinct conditions: (1) when reward was available
during the cue as expected or (2) when reward was unexpectedly omitted during the
cue. Pharmacological inactivation of the anterior PVT (aPVT), but not the
posterior PVT, increased sucrose seeking only when reward was omitted. Consistent
with this, photoactivation of aPVT neurons abolished sucrose seeking, and the
firing of aPVT neurons differentiated reward availability. Photoinhibition of
aPVT projections to the nucleus accumbens or to the amygdala increased or
decreased, respectively, sucrose seeking only when reward was omitted. Our
findings suggest that PVT bidirectionally modulates sucrose seeking under the
negative (frustrative) conditions of reward omission.
PMID- 28426971
TI - Metaplasticity as a Neural Substrate for Adaptive Learning and Choice under
Uncertainty.
AB - Value-based decision making often involves integration of reward outcomes over
time, but this becomes considerably more challenging if reward assignments on
alternative options are probabilistic and non-stationary. Despite the existence
of various models for optimally integrating reward under uncertainty, the
underlying neural mechanisms are still unknown. Here we propose that reward
dependent metaplasticity (RDMP) can provide a plausible mechanism for both
integration of reward under uncertainty and estimation of uncertainty itself. We
show that a model based on RDMP can robustly perform the probabilistic reversal
learning task via dynamic adjustment of learning based on reward feedback, while
changes in its activity signal unexpected uncertainty. The model predicts time
dependent and choice-specific learning rates that strongly depend on reward
history. Key predictions from this model were confirmed with behavioral data from
non-human primates. Overall, our results suggest that metaplasticity can provide
a neural substrate for adaptive learning and choice under uncertainty.
PMID- 28426972
TI - Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors
sensitize cancer stem cells to cisplatin and induces tumor senescence.
PMID- 28426973
TI - Non-linear enhancement of mRNA delivery efficiencies by influenza A derived NS1
protein engendering host gene inhibition property.
AB - Nucleic acid induced immunogenicity remains a significant impediment in
biomedical therapeutics because the innate immune system is a complex network
overlaid with functional redundancies. Herein we report that non-structural
protein 1 (NS1), an immune evasion protein derived from influenza A virus, when
co-delivered in mRNA format is a potent mRNA transfection enhancer without
toxicity. Transfection enhancement is mediated by NS1's effector domain through
inhibition of IRF3 and PKR, activators of early anti-viral responses as well as
CPSF30, a non immunostimulating protein. Importantly, host gene inhibition
mediated via CPSF30 inhibition is a highly effective immune evasion mechanism
because it blocks de novo gene expression non-specifically and inhibits global
anti-viral responses during mRNA transfection. We show that only NS1 with CPSF30
inhibition property can enhance modified mRNA transfections. Furthermore,
transfection efficiency of unmodified mRNA, if co-delivered with NS1-TX91 mRNA,
can exceed that of modified mRNA in HepG2, RAW 264.7 and HeLa cells. The novel
impact of NS1-TX91 lays the foundation of a virus inspired immune evasion genes
co-delivery approach that can address problems arising from RNA immunogenicity
for non-vaccine mRNA therapeutics in an affordable and scalable way. It is also
transferable to applications that benefits from active inhibition of material
induced immunogenicity.
PMID- 28426974
TI - Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal
therapy.
AB - Two of the challenges for clinical implementation of nano-therapeutic strategies
are optimization of tumor targeting and clearance of the nanoagents in vivo.
Herein, a cell-mediated therapy by transporting 2D Bi2Se3 nanosheets within
macrophage vehicles is described. The Bi2Se3 nanosheets with excellent near
infrared photothermal performance exhibit high macrophage uptake and negligible
cytotoxicity thus facilitating the fabrication of Bi2Se3-laden-macrophages.
Compared with bare Bi2Se3, the Bi2Se3-laden-macrophages after intravenous
injection show prolonged blood circulation and can overcome the hypoxia
associated drug delivery barrier to target the tumor efficiently and dramatically
enhance the efficiency of photothermal cancer therapy. The Bi2Se3-laden
macrophages possess good biocompatibility as demonstrated by the biochemical and
histological analyses and furthermore, most of the materials are excreted from
the body within 25 days. Our findings reveal a desirable system for highly
efficient near-infrared photothermal cancer therapy.
PMID- 28426975
TI - The regulation of the chloroplast proton motive force plays a key role for
photosynthesis in fluctuating light.
AB - Plants use sunlight as their primary energy source. During photosynthesis,
absorbed light energy generates reducing power by driving electron transfer
reactions. These are coupled to the transfer of protons into the thylakoid lumen,
generating a proton motive force (pmf) required for ATP synthesis. Sudden
alterations in light availability have to be met by regulatory mechanisms to
avoid the over-accumulation of reactive intermediates and maximize energy
efficiency. Here, the acidification of the lumen, as an intermediate product of
photosynthesis, plays an important role by regulating photosynthesis in response
to excitation energy levels. Recent findings reveal pmf regulation and the
modulation of its composition as key determinants for efficient photosynthesis,
plant growth, and survival in fluctuating light environments.
PMID- 28426976
TI - Alternative electron transport pathways in photosynthesis: a confluence of
regulation.
AB - Photosynthetic reactions proceed along a linear electron transfer chain linking
water oxidation at photosystem II (PSII) to CO2 reduction in the Calvin-Benson
Bassham cycle. Alternative pathways poise the electron carriers along the chain
in response to changing light, temperature and CO2 inputs, under prolonged
hydration stress and during development. We describe recent literature that
reports the physiological functions of new molecular players. Such highlights
include the flavodiiron proteins and their important role in the green lineage.
The parsing of the proton-motive force between DeltapH and Deltapsi, regulated in
many different ways (cyclic electron flow, ATPsynthase conductivity, ion/H+
transporters), is comprehensively reported. This review focuses on an integrated
description of alternative electron transfer pathways and how they contribute to
photosynthetic productivity in the context of plant fitness to the environment.
PMID- 28426977
TI - Blue/violet laser inactivates methicillin-resistant Staphylococcus aureus by
altering its transmembrane potential.
AB - The resistance of methicillin-resistant Staphylococcus aureus to antibiotics
presents serious clinical problems that prompted the need for finding alternative
or combination therapies. One such therapy is irradiation with blue light. To
determine the alterations in metabolic processes implicated in the observed
antimicrobial effects of blue light, we investigated the changes in membrane
potential and the presence of free-radical-producing photo-acceptor molecules.
Bacterial cultures irradiated with one or two doses of 405nm laser light (each
consisting of 121J/cm2) were imaged with spectrally resolved laser-scanning
microscopes to detect endogenous fluorescent species as well as the voltage
sensitive dye 3,3'-Diethyloxacarbocyanine iodide. The endogenous fluorescence
indicated the presence of photosensitizers (i.e., porphyrins, NADH, FAD) in the
cells, while the exogenous signal allowed us to monitor rapid changes in
transmembrane potential following treatment with light. The changes were drastic
within the first 5min after irradiation with the first dose and continued slowly
after the second irradiation. These results suggest that the early antimicrobial
activity of blue light results from alteration of membrane integrity with a
consequent decrease in membrane polarization and rapid alteration of vital
cellular functions. The observation of an early antimicrobial activity of light
is very encouraging, as it suggests that treatment does not necessarily have to
be administered over a long period of time.
PMID- 28426978
TI - Visualizing spatial distribution of small molecules in the rhubarb stalk (Rheum
rhabarbarum) by surface-transfer mass spectrometry imaging.
AB - Laser desorption/ionization mass spectrometry imaging (LDI-MSI) with gold
nanoparticle-enhanced target (AuNPET) was used for visualization of small
molecules in the rhubarb stalk (Rheum rhabarbarum L.). Analysis was focused on
spatial distribution of biologically active compounds which are found in rhubarb
species. Detected compounds belong to a very wide range of chemical compound
classes such as anthraquinone derivatives and their glucosides, stilbenes,
anthocyanins, flavonoids, polyphenols, organic acids, chromenes, chromanones,
chromone glycosides and vitamins. The analysis of the spatial distribution of
these compounds in rhubarb stalk with the nanoparticle-rich surface of AuNPET
target plate has been made without additional matrix and with minimal sample
preparation steps.
PMID- 28426979
TI - Response-based sleep intervention: Helping infants sleep without making them cry.
PMID- 28426980
TI - Hormonal and reproductive risk factors of papillary thyroid cancer: A population
based case-control study in France.
AB - The three times higher incidence of thyroid cancer in women compared to men
points to a role of female sex hormones in its etiology. However the effects of
these factors are poorly understood. We analyzed the association between thyroid
cancer and hormonal and reproductive factors among women enrolled in CATHY, a
population-based case-control study conducted in France. The study included 430
cases of papillary thyroid cancer and 505 controls frequency-matched on age and
area of residence. The odds ratios for thyroid cancer increased with age at
menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared
to premenopausal women, particularly if menopause followed an ovariectomy, and
for women with age at menopause <55years. In addition, use of oral contraceptives
and menopausal hormone therapy reduced the association with thyroid cancer by
about one third, and breastfeeding by 27%. Overall, these findings provide
evidence that the risk of thyroid cancer increases with later age at menarche and
after menopause, and decreases with use of oral contraceptives and menopausal
hormone therapy. These findings confirm an implication of hormonal factors in
papillary thyroid cancer risk, whose mechanisms need to be elucidated.
PMID- 28426981
TI - Overall survival in elderly patients with colorectal cancer: A population-based
study in the Caribbean.
AB - BACKGROUND: Population-based Cancer registries (PBCR) play an important role in
cancer surveillance and research. The aim of this study was to examine overall
survival in elderly patients with colorectal cancer (CRC) by analysing data from
the Martinique PBCR between 1993 and 2012. METHODS: The log-rank test was used to
assess the statistical differences of the survival curves by each categorical
variable: age at diagnosis, sex, histology, zone of residence, subsite, stage at
diagnosis, and chemotherapy. A multivariable Cox model was performed to identify
independent prognostic factors for overall survival in elderly patients with
colorectal cancer. RESULTS: Among 2230 patients included in the study, 60.8% were
aged>=65years; mean age at diagnosis of these patients was 75.7+/-7.2years. For
the period 2008-2012, 532 elderly patients were analysed; mean age of those
receiving chemotherapy was 73.0+/-0.4 versus 77.9+/-0.4years for those not
receiving chemotherapy (p<0.0001). Stage at diagnosis was evaluated in 87.8%
(467/532) of patients; 63.0% (294/467) had stage III-IV and 49.3% of these
patients (145/294) received chemotherapy. Chemotherapy was less frequently
prescribed in patients aged 75-84 and >=85 years as compared to those aged 65-74
years (41.1% and 15.0% versus 64.6% respectively; p<0.0001). Stage III-IV at
diagnosis (HR=5.25; 3.70-7.45; p<0.0001), and not receiving chemotherapy
(HR=3.05; 2.23-4.16; p<0.0001), were independent prognostic factors for overall
survival. CONCLUSION: Our study highlights the role of PBCR in evaluating cancer
survival and patterns of care in elderly people of the French West- Indies.
Chemotherapy was less frequently prescribed among the elderly.
PMID- 28426983
TI - Constraining the temporal variations of Ra isotopes and Rn in the groundwater end
member: Implications for derived SGD estimates.
AB - Submarine groundwater discharge (SGD) has been recognized as an important
supplier of chemical compounds to the ocean that may influence coastal
geochemical cycles. Radium isotopes (223Ra, 224Ra, 226Ra,228Ra) and radon (222Rn)
have been widely applied as tracers of SGD. Their application requires the
appropriate characterization of both the concentrations of tracers in the
discharging groundwater and their distribution in the coastal water column. This
study evaluates the temporal evolution of Ra isotopes and 222Rn concentrations in
a dynamic subterranean estuary of a microtidal Mediterranean coastal aquifer that
experiences large displacements of the fresh-saltwater interface as a necessary
initial step in evaluating the influence of SGD in coastal waters. We show that
changes in groundwater salinities due to the seaward displacement of the fresh
saltwater interface produced large variations in Ra activities in groundwater (by
a factor of ~19, ~14, ~6, and ~11 for 223Ra, 224Ra, 226Ra and 228Ra,
respectively), most importantly during rainfall events. In contrast, the 222Rn
activities in groundwater oscillated only by a factor of 3 during these rainy
periods. The large temporal variability in Ra activities hampers the
characterization of the SGD end-member when using Ra isotopes as tracers, and
thus presents a challenge for obtaining accurate SGD estimates. This study
emphasizes the need to understand the hydrodynamics of coastal aquifers to
appropriately constrain the Ra isotopes and 222Rn concentrations in groundwater
and when applying both tracers in dynamic microtidal coastal systems.
PMID- 28426982
TI - Redox environment in stem and differentiated cells: A quantitative approach.
AB - Stem cells are believed to maintain a specific intracellular redox status through
a combination of enhanced removal capacity and limited production of ROS. In the
present study, we challenge this assumption by developing a quantitative approach
for the analysis of the pro- and antioxidant ability of human embryonic stem
cells in comparison with their differentiated descendants, as well as adult stem
and non-stem cells. Our measurements showed that embryonic stem cells are
characterized by low ROS level, low rate of extracellular hydrogen peroxide
removal and low threshold for peroxide-induced cytotoxicity. However, biochemical
normalization of these parameters to cell volume/protein leads to matching of
normalized values in stem and differentiated cells and shows that tested in the
present study cells (human embryonic stem cells and their fibroblast-like
progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar
intracellular redox status. Based on these observations, we propose to use ROS
concentration averaged over the cell volume instead of ROS level as a measure of
intracellular redox balance. We show that attempts to use ROS level for
comparative analysis of redox status of morphologically different cells could
lead to false conclusions. Methods for the assessment of ROS concentration based
on flow cytometry analysis with the use of H2DCFDA dye and HyPer, genetically
encoded probe for hydrogen peroxide, are discussed.
PMID- 28426984
TI - Biomagnetic monitoring and element content of lichen transplants in a mixed land
use area of NE Italy.
AB - The aim of this study was to verify whether it is possible to discriminate
between the different pollution sources present in a mixed land use area of NE
Italy on the basis of the magnetic properties and the element content of lichen
transplants. Thalli of Pseudevernia furfuracea were collected in a pristine area
of the South-Eastern Alps and exposed for 2months in 40 sites located at the
knots of a 700m step grid covering ca. 40km2 of a mosaic of agricultural,
forested, industrial and urban areas. In this way, the samples could be analyzed
after a defined period of time, and compared to pre-exposure conditions. The post
exposure element content and the magnetic data substantially agreed, revealing a
rather modest anthropogenic impact on the territory, mostly limited to an
industrial park. Since the magnetic mineralogy was homogeneous throughout the
entire set of samples, with magnetite-like minerals as the main magnetic
carriers, it was not possible to discriminate between PM originating from the
different pollution sources. The contribution given by the industrial park could
be confirmed by the multivariate analysis of the element data set. Conversely, it
was possible to assess the low environmental impact of the largest local
industry, a cement plant, located outside the industrial park. Notwithstanding
the relatively short time of the survey, P. furfuracea was proven to be an
effective accumulator for biomagnetic monitoring studies, its magnetic properties
being excellent proxies for heavy metal pollution even when the anthropogenic
impact on the territory is low.
PMID- 28426985
TI - Current uses of ground penetrating radar in groundwater-dependent ecosystems
research.
AB - Ground penetrating radar (GPR) is a high-resolution technique widely used in
shallow groundwater prospecting. This makes GPR ideal to characterize the
hydrogeological functioning of groundwater-dependent ecosystems (GDE). This paper
reviews current uses of GPR in GDE research through the construction of a
database comprising 91 worldwide GPR case studies selected from the literature
and classified according to (1) geological environments favouring GDE; (2)
hydrogeological research interests; and (3) field technical and (4)
hydrogeological conditions of the survey. The database analysis showed that
inland alluvial, colluvial, and glacial formations were the most widely covered
geological environments. Water-table depth was the most repeated research
interest. By contrast, weathered-marl and crystalline-rock environments as well
as the delineation of salinity interfaces in coastal and inland areas were less
studied. Despite that shallow groundwater propitiated GDE in almost all the GPR
case studies compiled, only one case expressly addressed GDE research. Common
ranges of prospecting depth, water-table depth, and volumetric water content
deduced by GPR and other techniques were identified. Antenna frequency of 100MHz
and the common offset acquisition technique predominated in the database. Most of
GPR case studies were in 30-50 degrees N temperate latitudes, mainly in Europe
and North America. Eight original radargrams were selected from several GPR
profiles performed in 2014 and 2015 to document database classes and identified
gaps, as well as to define experimental ranges of operability in GDE
environments. The results contribute to the design of proper GPR surveys in GDE
research.
PMID- 28426986
TI - Schrodinger's code-script: not a genetic cipher but a code of development.
AB - In his book What is Life? Erwin Schrodinger coined the term 'code-script',
thought by some to be the first published suggestion of a hereditary code and
perhaps a forerunner of the genetic code. The etymology of 'code' suggests three
meanings relevant to 'code-script which we distinguish as 'cipher-code', 'word
code' and 'rule-code'. Cipher-codes and word-codes entail translation of one set
of characters into another. The genetic code comprises not one but two cipher
codes: the first is the DNA 'base-pairing cipher'; the second is the 'nucleotide
amino-acid cipher', which involves the translation of DNA base sequences into
amino-acid sequences. We suggest that Schrodinger's code-script is a form of
'rule-code', a set of rules that, like the 'highway code' or 'penal code',
requires no translation of a message. Schrodinger first relates his code-script
to chromosomal genes made of protein. Ignorant of its properties, however, he
later abandons 'protein' and adopts in its place a hypothetical, isomeric
'aperiodic solid' whose atoms he imagines rearranged in countless different
conformations, which together are responsible for the patterns of ontogenetic
development. In an attempt to explain the large number of combinations required,
Schrodinger referred to the Morse code (a cipher) but in doing so unwittingly
misled readers into believing that he intended a cipher-code resembling the
genetic code. We argue that the modern equivalent of Schrodinger's code-script is
a rule-code of organismal development based largely on the synthesis, folding,
properties and interactions of numerous proteins, each performing a specific
task.
PMID- 28426987
TI - A review on nitrous oxide (N2O) emissions during biological nutrient removal from
municipal wastewater and sludge reject water.
AB - Nitrous oxide (N2O) is an important pollutant which is emitted during the
biological nutrient removal (BNR) processes of wastewater treatment. Since it has
a greenhouse effect which is 265 times higher than carbon dioxide, even
relatively small amounts can result in a significant carbon footprint. Biological
nitrogen (N) removal conventionally occurs with nitrification/denitrification,
yet also through advanced processes such as nitritation/denitritation and
completely autotrophic N-removal. The microbial pathways leading to the N2O
emission include hydroxylamine oxidation and nitrifier denitrification, both
activated by ammonia oxidizing bacteria, and heterotrophic denitrification. In
this work, a critical review of the existing literature on N2O emissions during
BNR is presented focusing on the most contributing parameters. Various factors
increasing the N2O emissions either per se or combined are identified: low
dissolved oxygen, high nitrite accumulation, low chemical oxygen demand to
nitrogen ratio, slow growth of denitrifying bacteria, uncontrolled pH and
temperature. However, there is no common pattern in reporting the N2O generation
amongst the cited studies, a fact that complicates its evaluation. When
simulating N2O emissions, all microbial pathways along with the potential
contribution of abiotic N2O production during wastewater treatment at different
dissolved oxygen/nitrite levels should be considered. The undeniable validation
of the robustness of such models calls for reliable quantification techniques
which simultaneously describe dissolved and gaseous N2O dynamics. Thus, the
choice of the N-removal process, the optimal selection of operational parameters
and the establishment of validated dynamic models combining multiple N2O pathways
are essential for studying the emissions mitigation.
PMID- 28426988
TI - Solar photocatalytic application of NbO2OH as alternative photocatalyst for water
treatment.
AB - Water recycling and industrial effluents remediation are a hot topic of research
to reduce the environmental impact of the human activity. Persistent organic
pollutants are highly recalcitrant compounds with hazardous effects associated to
their fate in water bodies. Several novel technologies have been developed during
the last decades to deal with this novel contamination. However, the natural
sources and idiosyncrasy of each country lead to the potential application of
different technologies. In this context, we have focused on the development of
phocotalytic treatment of solutions containing dyes using a novel photocatalytic
material, the NbO2OH. The NbO2OH was synthesized and characterized with different
techniques. Several assays demonstrated the solar photoactivity of this novel
oxyhydroxide catalyst, achieving complete decolorizations after 10min of
treatment under optimal conditions of 1.0gL-1 NbO2OH photocatalyst loading, 0.1M
of H2O2 as electron scavenger, pH4.0 and methyl orange concentrations up to 15mgL
1. Also, the catalyst recuperation demonstrated the potential reuse of this
photocatalyst without losing catalytic response after five cycles. This work is
of significant importance because niobium is a natural resource, mainly extracted
in Brazil and the annual global sunlight irradiation in the near-equatorial
region of northeast Brazil is over the average solar irradiation of the planet.
Thus, the solar photocatalytic treatment using NbO2OH in northeast Brazil appears
as a highly potential environmental-friendly nanotechnology to mitigate the water
pollution.
PMID- 28426989
TI - The thermal impact of subsurface building structures on urban groundwater
resources - A paradigmatic example.
AB - Shallow subsurface thermal regimes in urban areas are increasingly impacted by
anthropogenic activities, which include infrastructure development like
underground traffic lines as well as industrial and residential subsurface
buildings. In combination with the progressive use of shallow geothermal energy
systems, this results in the so-called subsurface urban heat island effect. This
article emphasizes the importance of considering the thermal impact of subsurface
structures, which commonly is underestimated due to missing information and of
reliable subsurface temperature data. Based on synthetic heat-transport models
different settings of the urban environment were investigated, including: (1)
hydraulic gradients and conductivities, which result in different groundwater
flow velocities; (2) aquifer properties like groundwater thickness to aquitard
and depth to water table; and (3) constructional features, such as building
depths and thermal properties of building structures. Our results demonstrate
that with rising groundwater flow velocities, the heat-load from building
structures increase, whereas down-gradient groundwater temperatures decrease.
Thermal impacts on subsurface resources therefore have to be related to the
permeability of aquifers and hydraulic boundary conditions. In regard to the
urban settings of Basel, Switzerland, flow velocities of around 1 md-1 delineate
a marker where either down-gradient temperature deviations or heat-loads into the
subsurface are more relevant. Furthermore, no direct thermal influence on
groundwater resources should be expected for aquifers with groundwater
thicknesses larger 10m and when the distance of the building structure to the
groundwater table is higher than around 10m. We demonstrate that measuring
temperature changes down-gradient of subsurface structures is insufficient
overall to assess thermal impacts, particularly in urban areas. Moreover, in
areas which are densely urbanized, and where groundwater flow velocities are low,
appropriate measures for assessing thermal impacts should specifically include a
quantification of heat-loads into the subsurface which result in a more diffuse
thermal contamination of urban groundwater resources.
PMID- 28426990
TI - Concentration of perfluorinated compounds and cotinine in human foetal organs,
placenta, and maternal plasma.
AB - BACKGROUND: Perfluoroalkyl substances (PFASs) are bio-accumulative pollutants,
and prenatal exposure to PFASs is believed to impact human foetal development and
may have long-term adverse health effects later in life. Additionally, maternal
cigarette smoking may be associated with PFAS levels. Foetal exposure has
previously been estimated from umbilical cord plasma, but the actual
concentration in foetal organs has never been measured. OBJECTIVES: The
concentrations of 5 PFASs and cotinine - the primary metabolite of nicotine -
were measured in human foetuses, placentas, and maternal plasma to evaluate to
what extent these compounds were transferred from mother to foetus and to
determine if the PFAS concentrations were associated with maternal cigarette
smoking. METHODS: Thirty-nine Danish women who underwent legal termination of
pregnancy before gestational week 12 were included; 24 maternal blood samples
were obtained together with 34 placental samples and 108 foetal organs. PFASs and
cotinine were assayed by liquid chromatography/triple quadrupole mass
spectrometry. RESULTS: In foetal organs, the average concentrations of
perfluorooctanesulphonic acid (PFOS), perfluorooctanoic acid (PFOA),
perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDa), and
perfluorodecanoic acid (PFDA) were 0.6ng/g, 0.2ng/g, 0.1ng/g, 0.1ng/g, and
0.1ng/g, respectively. A significant positive correlation was found between the
exposure duration, defined as foetal age, and foetal to maternal ratio for all
five PFASs and cotinine. Smokers presented 99ng/g cotinine in plasma, 108ng/g in
placenta, and 61ng/g in foetal organs. No correlation between the maternal
cotinine concentrations and PFAS concentrations was found. CONCLUSIONS: PFASs
were transferred from mother to foetus, however, with different efficiencies. The
concentrations of PFOS, PFOA, PFNA, PFUnDA, and PFDA in foetal organs were much
lower than the maternal concentrations. Furthermore, a significant correlation
between the exposure duration and all of the evaluated PFASs was found. The
health-compromising concentrations of these substances during foetal development
are unknown.
PMID- 28426991
TI - Clinical usefulness of 18F-FDG PET/CT for initial staging and assessment of
treatment efficacy in patients with lymph node tuberculosis.
AB - INTRODUCTION: Few studies have evaluated the promising role of 18F-fluoro-2-deoxy
D-glucose positron emission tomography (PET) and PET/computed tomography FDG
PET/CT in evaluating and monitoring treatment response in patients with lymph
node tuberculosis (LNTB). The aim of this clinical investigation was to assess
the clinical usefulness of FDG PET/CT for initial tuberculosis staging and to
determine the prognostic value of the decrease of 18F-FDG uptake during
antibiotic treatment in LNTB patients. METHODS: We retrospectively reviewed 18
cases of LNTB admitted at a single center from 2004 to 2014. Medical records of
patients who underwent two FDG PET/CT (>6 months interval), at initial staging
and at the end of therapy were reviewed to determine the impact of FDG PET/CT on
initial management of LNTB and response to therapy. Statistical analysis was
performed using linear mixed-effects model. RESULTS: Thirteen cases of
disseminated LNTB and five cases of localized LNTB were included in the study.
Initial FDG PET/CT allowed guided biopsy for initial diagnosis in 5 patients and
identified unknown extra-LN TB sites in 9 patients. Visual analysis follow-up of
FDG PET/CT showed a complete metabolic response in 9/18 patients (all of whom
were cured), a partial response in 7/18 (5 of whom were cured) and no response in
2/18 (all of whom were not cured). The semi-quantitative evaluation of 18F-FDG
intensity decrease based on the maximum standardized uptake value (SUVmax),
compared to targeted estimated decrease allowed to predict correctly a complete
response to treatment in 14/18 cases. CONCLUSION: FDG PET/CT allows an accurate
pre-therapeutic mapping of LNTB and helps for early TB confirmation. The SUVmax
follow up is a potential tool for monitoring the treatment response.
PMID- 28426992
TI - Factors affecting sound energy absorbance in acute otitis media model of
chinchilla.
AB - Acute otitis media (AOM) is a rapid-onset infection of the middle ear which
results in middle ear pressure (MEP), middle ear effusion (MEE), and structural
changes in middle ear tissues. Previous studies from our laboratory have
identified that MEP, MEE, and middle ear structural changes are three factors
affecting tympanic membrane (TM) mobility and hearing levels (Guan et al., 2014,
2013). Sound energy reflectance or absorbance (EA) is a diagnostic tool
increasingly used in clinical settings for the identification of middle ear
diseases. However, it is unclear whether EA can differentiate these three factors
in an AOM ear. Here we report wideband EA measurements in the AOM model of
chinchilla at three experimental stages: unopened, pressure released, and
effusion removed. These correspond to the combined and individual effects of the
three factors on sound energy transmission. AOM was produced by transbullar
injection of Haemophilus influenzae in two treatment groups: 4 days (4D) and 8
days (8D) post inoculation. These time points represent the relatively early and
later phase of AOM. In each group of chinchillas, EA at 250-8000 Hz was measured
using a wideband tympanometer at three experimental stages. Results show that the
effects of MEP, MEE, and tissue structural changes over the frequency range
varied with the disease time course. MEP was the primary contributor to reduction
of EA in 4D AOM ears and had a smaller effect in 8D ears. MEE reduced the EA at 6
8 kHz in 4D ears and 2-8 kHz in 8D ears and was responsible for the EA peak in
both 4D and 8D ears. The residual EA loss due to structural changes was observed
over the frequency range in 8D ears and only at high frequencies in 4D ears. The
EA measurements were also compared with the published TM mobility loss in
chinchilla AOM ears.
PMID- 28426993
TI - A new combined method of stable isotope-labeling derivatization-ultrasound
assisted dispersive liquid-liquid microextraction for the determination of
neurotransmitters in rat brain microdialysates by ultra high performance liquid
chromatography tandem mass spectrometry.
AB - In this work, for the first time, a new hyphenated technique of stable isotope
labeling derivatization-ultrasound-assisted dispersive liquid-liquid
microextraction has been developed for the simultaneous determination of
monoamine neurotransmitters (MANTs) and their biosynthesis precursors and
metabolites. The developed method was based on ultra high performance liquid
chromatography tandem mass spectrometry detection using multiple-reaction
monitoring mode. A pair of mass spectrometry sensitizing reagents, d0-10-methyl
acridone-2-sulfonyl chloride and d3-10-methyl-acridone-2-sulfonyl chloride, as
stable isotope probes was utilized to facilely label neurotransmitters,
respectively. The heavy labeled MANTs standards were prepared and used as
internal standards for quantification to minimize the matrix effects in mass
spectrometry analysis. Low toxic bromobenzene (extractant) and acetonitrile
(dispersant) were utilized in microextraction procedure. Under the optimized
conditions, good linearity was observed with the limits of detection (S/N>3) and
limits of quantification (S/N>10) in the range of 0.002-0.010 and 0.015
0.040nmol/L, respectively. Meanwhile, it also brought acceptable precision (4.2
8.8%, peak area RSDs %) and accuracy (recovery, 96.9-104.1%) results. This method
was successfully applied to the simultaneous determination of monoamine
neurotransmitters and their biosynthesis precursors and metabolites in rat brain
microdialysates of Parkinson's disease and normal rats. This provided a new
method for the neurotransmitters related studies in the future.
PMID- 28426994
TI - Silica nanoparticles induced intrinsic apoptosis in neuroblastoma SH-SY5Y cells
via CytC/Apaf-1 pathway.
AB - The present study was to investigate effects of Silica nanoparticles (SiNPs) on
nervous system and explore potential mechanisms in human neuroblastoma cells (SH
SY5Y). Cytotoxicity was detected by cell viability and Lactate dehydrogenase
(LDH) release. Flow cytometry analysis was applied to assess mitochondrial
membrane potential (MMP) loss, intracellular Ca2+ and apoptosis. To clarify the
mechanism of SiNPs-induced apoptosis, intrinsic apoptosis-related proteins were
detected. Our results showed that SiNPs caused cytotoxicity, cell membrane damage
and Ca2+ increase in a dose-dependent manner in SH-SY5Y cells. Both the
mitochondrial membrane potential (MMP) loss and potential mitochondria damage
resulted in Cyt C release to the cytoplasm. The elevated Cyt C and Apaf1 further
triggered intrinsic apoptosis via executive molecular caspase-9 and caspase-3.
The present study confirmed that SiNPs induced intrinsic apoptosis in
neuroblastoma SH-SY5Y cells via CytC/Apaf-1 pathway and provided a better
understanding of the potential toxicity induced by SiNPs on human neurocyte.
PMID- 28426995
TI - Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N
methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action.
AB - The emergence of multidrug-resistant bacteria causes an urgent need for new
generation of antibiotics, which may have a different mechanism of inhibition or
killing action from the existing. Targeting at the inhibition of bacterial cell
division via the control of FtsZ function is one of the effective and promising
approaches. Some natural extracts from plants such as sanguinarine and berberine
(analogs of pyridinium compounds) are known to alter FtsZ function. In this
study, a series of novel quaternary pyridinium compounds was constructed based on
the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline
derivatives and their antibacterial activity against nine significant pathogens
was investigated using broth microdilution method. In the in vitro assay, the
compounds showed strong antibacterial activities against various testing strains,
which include some drug-resistant strains such as methicillin-resistant S. aureus
and vancomycin-resistant E. faecium. Our results of morphology change of B.
subtilis cells and molecular docking proved that the compounds functioned as an
effective inhibitor to suppress FtsZ polymerization and FtsZ GTPase activity and
thus the compound stops cell division and cause cell death through interacting
with C-terminal interdomain cleft of FtsZ.
PMID- 28426996
TI - Design, synthesis, SAR discussion, in vitro and in vivo evaluation of novel
selective EGFR modulator to inhibit L858R/T790M double mutants.
AB - Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of
5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and
synthesized with the purpose to overcome the drug resistance resulted from
T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme
inhibitory activities and selectivity with sub nanomolar IC50 values for both the
single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold
selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities
and pharmacokinetic properties and lower binding affinity to hERG ion channel
than AZD9291 and displayed strong antiproliferative activity against the H1975
non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo
anticancer efficacy in a human NSCLC (H1975) xenograft mouse model.
PMID- 28426997
TI - Design and synthesis of neolamellarin a derivatives targeting heat shock protein
90.
AB - In this study, we designed and synthesized a novel family of neolamellarin A
derivatives that showed high inhibitory activity toward heat shock protein 90
(Hsp90), a kinase associated with cell proliferation. The 3,4
bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N
position of pyrrole are essential to the Hsp90 inhibitory activity and
cytotoxicity of these compounds. Western blot analysis demonstrated that these
compounds induced dramatic depletion of the examined client proteins of Hsp90,
and accelerated cancer cell apoptosis. Docking simulations suggested that the
binding mode of 9p was similar to that of the VER49009, a potent inhibitor of
Hsp90. Further molecular dynamics simulation indicated that the hydrophobic
interactions as well as the hydrogen bonds contributed to the high affinity of 9p
to Hsp90.
PMID- 28426998
TI - Can nursing students' perceived teacher enthusiasm dampen their class-related
boredom during theoretical lessons? A cross-sectional study among Chinese nursing
students.
AB - BACKGROUND: Class-related boredom experienced by nursing students during
theoretical lessons may affect their health and learning outcomes. Perceived
teacher enthusiasm of nursing students may dampen their boredom, but little
empirical research has investigated their relationship. OBJECTIVES: The aim of
the current study is to investigate the dampening effects of nursing students'
perceived teacher enthusiasm on their class-related boredom during theoretical
lessons. The main theoretical framework is control-value theory of achievement
emotions. DESIGN: A cross-sectional survey was used. METHODS: 352 nursing
students during their theoretical lessons completed questionnaires on perceived
teacher enthusiasm, boredom proneness, perceived task difficulty and class
related boredom. Correlation and classic multiple hierarchical analysis results
supported the hypothesis about the relationships among variables. RESULTS: After
controlling the effects of demographic variables, boredom proneness and perceived
task difficulty, perceived teacher enthusiasm negatively predicted class-related
boredom significantly. CONCLUSION: Perceived teacher enthusiasm of nursing
students can predict their class-related boredom significantly.
PMID- 28426999
TI - Emotional intelligence and affective events in nurse education: A narrative
review.
AB - OBJECTIVE: To investigate the current state of knowledge about emotional
intelligence and affective events that arise during nursing students' clinical
placement experiences. DESIGN: Narrative literature review. DATA SOURCES: CINAHL,
MEDLINE, PsycINFO, Scopus, Web of Science, ERIC and APAIS-Health databases
published in English between 1990 and 2016. REVIEW METHODS: Data extraction from
and constant comparative analysis of ten (10) research articles. RESULTS: We
found four main themes: (1) emotional intelligence buffers stress; (2) emotional
intelligence reduces anxiety associated with end of life care; (3) emotional
intelligence promotes effective communication; and (4) emotional intelligence
improves nursing performance. CONCLUSIONS: The articles we analysed adopted a
variety of emotional intelligence models. Using the Ashkanasy and Daus "three
stream" taxonomy (Stream 1: ability models; 2: self-report; 3: mixed models), we
found that Stream 2 self-report measures were the most popular followed by Stream
3 mixed model measures. None of the studies we surveyed used the Stream 1
approach. Findings nonetheless indicated that emotional intelligence was
important in maintaining physical and psychological well-being. We concluded that
developing emotional intelligence should be a useful adjunct to improve academic
and clinical performance and to reduce the risk of emotional distress during
clinical placement experiences. We call for more consistency in the use of
emotional intelligence tests as a means to create an empirical evidence base in
the field of nurse education.
PMID- 28427000
TI - Psychological maltreatment, coping strategies, and mental health problems: A
brief and effective measure of psychological maltreatment in adolescents.
AB - Psychological maltreatment is an important social and public health problem and
associated with a wide range of short and long-term outcomes in childhood to
adulthood. Given the importance of investigating mitigating factors on its
effect, the purpose of the present study is to investigate the mediating effect
of active and avoidant coping strategies on the association between psychological
maltreatment and mental health- internalizing and externalizing- problems in
adolescents. Participants of the study consisted of 783 adolescents, ranging in
age from 14 to 18 years (M=15.57, SD=0.88), with 52.9% female and 47.1% male.
Several structural equation models were conducted to investigate the mediating
role of coping strategies on the effect of psychological maltreatment on
adolescents' internalizing and externalizing problems. Findings from mediation
analyses demonstrated the mediating effect of active and avoidant coping
strategies on the association between psychological maltreatment and mental
health problems. The outcomes support adolescents use more avoidant coping
strategies and fewer active coping strategies in the face of psychological
maltreatment experiences, and this affects their mental health. Taken together,
these results should contribute to the design of prevention and intervention
services in order to promote mental health.
PMID- 28427001
TI - Emergency room thoracotomy for acute traumatic cardiac tamponade caused by a
blunt cardiac injury: A case report.
AB - INTRODUCTION: Traumatic blunt cardiac injuries have a high mortality rate, and
prompt diagnosis and treatment can be lifesaving in cardiac tamponade.
PRESENTATION OF CASE: A 62-year-old man was transferred to the emergency
department after a motor vehicle accident. He was hemodynamically unstable. A
focused assessment with sonography in trauma (FAST) showed pericardial fluid with
right ventricular collapse consistent with cardiac tamponade in the subxiphoid
view. He collapsed despite a subxiphoid pericardiotomy. Owing to the ongoing
hemodynamic instability, we performed a left anterolateral thoracotomy. Direct
incision of the pericardium showed blood and clots within the pericardial space,
indicating hemopericardium. The heart stroke and hemodynamic status recovered on
removing the clot. DISCUSSION: Although the physical findings of cardiac
tamponade are not always apparent in life-threatening acute cardiac tamponade
after blunt trauma, FAST is a reliable tool for diagnosing and following cardiac
tamponade. A median sternotomy is a standard approach for evaluating cardiac
injury in hemodynamically stable patients with or without cardiopulmonary bypass.
However, a left anterior thoracotomy was the fastest, simplest life-saving
procedure considering the need for open-chest cardiac massage given our patient's
life-threatening condition. CONCLUSION: A prompt diagnosis using FAST and
treatment can be lifesaving in traumatic acute cardiac tamponade. A
pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac
decompression in acute traumatic cardiac tamponade in cases of ineffective
drainage due to clot formation within the pericardial space.
PMID- 28427002
TI - Incidental posterior mediastinal paraganglioma: The safe approach to management,
case report.
AB - INTRODUCTION: Paragangliomas are neuroendocrine tumors arising from chromaffin
cells located in sympathetic paraganglia. Mediastinal paragangliomas are
extremely rare and can be classified as functional or non-functional according to
their ability for secreting catecholamines. Patients can be asymptomatic and the
diagnosis is usually incidental. Complete surgical resection remains the standard
of care for paragangliomas. PRESENTATION OF CASE: We present a 44-year-old woman
with a functional mediastinal paraganglioma incidentally found during the
perioperative imaging workup for a diagnosed breast carcinoma. Chest radiograph
and computed tomography (CT) showed a well-defined lesion in the posterior
mediastinum suspicious for an esophageal malignancy. Endoscopic and CT-guided
biopsies were performed confirming the diagnosis of a neuroendocrine tumor.
Laboratory studies showed elevated catecholamines and chromogranin A levels,
consistent with a paraganglioma. Appropriate pre-operative management was done
and successful surgical resection without catecholamine related complications was
achieved. DISCUSSION: The workup and treatment of incidentally discovered adrenal
and extra-adrenal lesions are controversial. Because of the absence of symptoms
and the wider differential diagnosis of extra-adrenal lesions, an attempt for
biopsying and surgically remove these lesions prior to biochemical testing is not
an uncommon scenario, although this could be potentially harmful. Surgeons should
have an index of suspicion for catecholamine-secreting tumors and hormonal levels
should be assessed prior to biopsy or surgical resection. CONCLUSION: Surgeons
should consider paragangliomas as a differential diagnosis for extra-adrenal
lesions. Biochemical testing with catecholamines and chromogranin A levels should
be performed prior to biopsy or surgical removal in order to avoid catastrophic
complications.
PMID- 28427003
TI - CE method for the in-process control of the synthesis of active substances
conjugated with gold nanoparticles.
AB - A fast capillary electrophoresis method was developed and validated for the in
process control (IPC) of the synthesis of active substances (APIs) with gold
nanoparticles (AuNPs). The capillary electrophoresis method was key to ensure
that the reaction step conducted in order to obtain AuNP and API conjugates will
produce the expected product without the presence of free APIs, which is a
critical parameter determining the quality of the synthetic material. Capillary
electrophoresis was performed using uncoated fused-silica capillaries with the
effective length of 40cm, 50MUm i.d. and the background electrolyte consisted of
20mM borate buffer (pH 8.5) with the application of hydrodynamic injection
50mbar/5s, voltage 20kV, temperature of the capillary cassette 25 degrees C and
UV detection at 261nm for GE, 541nm for AuNP-GE, 227nm for PE and 535nm for AuNP
PE. During validation the specificity, linearity, accuracy, precision, range, and
stability of the sample solution were confirmed. The linear regression (R2=0.999)
between the corrected peak areas of the analytes and their amount was fulfilled
in the range from 2.4MUg/mL to 0.3mg/mL for genistein and from 4.6MUg/mL to
0.6mg/mL for pemetrexed. Within this range the method was proved to be accurate
(99.0% for genistein and 99.9% for pemetrexed) and precise for both analytes with
the intra-day RSD values of 0.77% and 0.97% for the migration time of genistein
and pemetrexed, respectively. The inter-day RSD values were 1.90% and 2.27% for
the migration time of genistein and pemetrexed, respectively. The LOD and LOQ
values for pemetrexed were 1.4MUg/mL and 4.6MUg/mL, respectively, and for
genistein 0.72MUg/mL and 2.4MUg/mL, respectively. The results obtained during the
validation indicate that the method is sufficient to be applied for the IPC of
the synthesis of APIs with gold nanoparticles.
PMID- 28427004
TI - Enzymatic activity of the CaM-PDE1 system upon addition of actinyl ions.
AB - The threat of a dirty bomb which could cause internal contamination has been of
major concern for the past decades. Because of their high chemical toxicity and
their presence in the nuclear fuel cycle, uranium and neptunium are two actinides
of high interest. Calmodulin (CaM) which is a ubiquitous protein present in all
eukaryotic cells and is involved in calcium-dependent signaling pathways has a
known affinity for uranyl and neptunyl ions. The impact of the complexation of
these actinides on the physiological response of the protein remains, however,
largely unknown. An isothermal titration calorimetry (ITC) was developed to
monitor in vitro the enzymatic activity of the phosphodiesterase enzyme which is
known to be activated by CaM and calcium. This approach showed that addition of
actinyl ions (AnO2n+), uranyl (UO22+) and neptunyl (NpO2+), resulted in a
decrease of the enzymatic activity, due to the formation of CaM-actinide
complexes, which inhibit the enzyme and alter its interaction with the substrate
by direct interaction. Results from dynamic light scattering rationalized this
result by showing that the CaM-actinyl complexes adopted a specific conformation
different from that of the CaM-Ca2+ complex. The effect of actinides could be
reversed using a hydroxypyridonate actinide decorporation agent (5-LIO(Me-3,2
HOPO)) in the experimental medium demonstrating its capacity to efficiently bind
the actinides and restore the calcium-dependent enzyme activation.
PMID- 28427005
TI - Diagnostic accuracy of magnetic resonance imaging in patients with suspected
pulmonary embolism: A bivariate meta-analysis.
AB - BACKGROUND: Computed tomographic pulmonary angiography (CTPA) has simplified the
diagnostic approach to patients with clinically suspected pulmonary embolism
(PE), but alternative imaging tests are still advocated. We aimed to
systematically assess the diagnostic accuracy of magnetic resonance imaging (MRI)
for PE diagnosis. METHODS: Studies evaluating the diagnostic accuracy of MRI for
the diagnosis of PE were systematically searched in the PubMed and EMBASE
databases (up to May 2016). QUADAS - 2 tool was used for the quality assessment
of the primary studies. A bivariate random-effects regression approach was used
for summary estimates of both sensitivity and specificity. RESULTS: Thirteen
studies, for a total of 1170 patients, were included. Weighted mean prevalence of
PE was 37% at random-effect model. Weighted mean inconclusive MRI results were
19% at random-effect model. After exclusion of technical inadequate results, MRI
bivariate weighted mean sensitivity was 80.9% (95% confidence interval [CI] 68.2,
89.4%), with a bivariate weighted mean specificity of 96.4% (95% CI 92.4, 98.3%),
CONCLUSIONS: MRI has high specificity but limited sensitivity for the diagnosis
of PE. Inconclusive results are a major limitation to the practical application
of MRI. Management studies are needed to more precisely define the role of MRI in
the diagnostic workup of patients with suspected PE.
PMID- 28427006
TI - Regeneration of pilot-scale ion exchange columns for hexavalent chromium removal.
AB - Due to stricter regulations, some drinking water utilities must implement
additional treatment processes to meet potable water standards for hexavalent
chromium (Cr(VI)), such as the California limit of 10 MUg/L. Strong base anion
exchange is effective for Cr(VI) removal, but efficient resin regeneration and
waste minimization are important for operational, economic and environmental
considerations. This study compared multiple regeneration methods on pilot-scale
columns on the basis of regeneration efficiency, waste production and salt usage.
A conventional 1-Stage regeneration using 2 N sodium chloride (NaCl) was compared
to 1) a 2-Stage process with 0.2 N NaCl followed by 2 N NaCl and 2) a mixed
regenerant solution with 2 N NaCl and 0.2 N sodium bicarbonate. All methods
eluted similar cumulative amounts of chromium with 2 N NaCl. The 2-Stage process
eluted an additional 20-30% of chromium in the 0.2 N fraction, but total resin
capacity is unaffected if this fraction is recycled to the ion exchange
headworks. The 2-Stage approach selectively eluted bicarbonate and sulfate with
0.2 N NaCl before regeneration using 2 N NaCl. Regeneration approach impacted the
elution efficiency of both uranium and vanadium. Regeneration without co-eluting
sulfate and bicarbonate led to incomplete uranium elution and potential formation
of insoluble uranium hydroxides that could lead to long-term resin fouling,
decreased capacity and render the resin a low-level radioactive solid waste.
Partial vanadium elution occurred during regeneration due to co-eluting sulfate
suppressing vanadium release. Waste production and salt usage were comparable for
the 1- and 2-Stage regeneration processes with similar operational setpoints with
respect to chromium or nitrate elution.
PMID- 28427007
TI - Novel and revisited approaches in antituberculosis drug discovery.
AB - The increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (Mtb)
necessitates the discovery and development of novel drugs against tuberculosis.
In this review, we focus on two recent approaches that led to the discovery of
promising antitubercular compound classes: (I) Hits derived from large compound
library screens are increasingly difficult to translate into clinical
application; this in turn fostered the development of innovative screening
methods. (II) An alternative strategy towards high-quality hits and leads is to
evaluate chemically diverse scaffolds which can be found among natural products.
The so-called rekindling and repurposing approaches were particularly fruitful in
the last few years.
PMID- 28427008
TI - Lateral hypothalamic circuits for sleep-wake control.
AB - The lateral hypothalamic area (LHA) of the diencephalon is crucially involved in
controlling instinctive behavior such as sleep-wake cycle and feeding behavior.
LHA is a heterogeneous structure that contains spatially intermingled,
genetically distinct cell populations. Among LHA neurons, orexin/hypocretin (OX)
neuron is the key cell type that promotes waking, and specific loss of OX neurons
results in narcolepsy. Melanin-concentrating hormone (MCH) containing neurons are
known to be active during rapid eye movement (REM) sleep and stimulation of these
neurons promotes REM sleep. Here we review the classical and more recent findings
in this field and discuss the molecular and cellular network organization of LHA
neurons that could ultimately regulate the switch between wakefulness and general
states of sleep.
PMID- 28427009
TI - Early-in-life dietary zinc deficiency and supplementation and mammary tumor
development in adulthood female rats.
AB - Zinc deficiency during pregnancy and postnatal life can adversely increase risk
of developing human diseases at adulthood. The present study was designed to
evaluate whether dietary zinc deficiency or supplementation during the pregnancy,
lactation and juvenile stages interferes in the development of mammary tumors
induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats.
Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA
- 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented
diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters'
weaning. Female offspring received the same diets as their dams until postnatal
day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg,
ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor
samples were processed for histological evaluation and gene expression microarray
analysis. The ZnD induced a significant reduction in female offspring body weight
evolution and in mammary gland development. At late in life, the ZnD or ZnS did
not alter the latency, incidence, multiplicity, volume or histological types of
mammary tumors in relation to the ZnA group. However, the total tumor number in
ZnS group was higher than in ZnA group, accompanied by distinct expression of 4
genes up- and 15 genes down-regulated. The present findings indicate that early
in-life dietary zinc supplementation, differently to zinc deficiency, has a
potential to modify the susceptibility to the development of mammary tumors
induced by DMBA.
PMID- 28427011
TI - Biosensors for the monitoring of harmful algal blooms.
AB - Harmful algal blooms (HABs) are a major global concern due to their propensity to
cause environmental damage, healthcare issues and economic losses. In particular,
the presence of toxic phytoplankton is a cause for concern. Current HAB
monitoring programs often involve laborious laboratory-based analysis at a high
cost and with long turnaround times. The latter also hampers the potential to
develop accurate and reliable models that can predict HAB occurrence. However, a
promising solution for this issue may be in the form of remotely deployed
biosensors, which can rapidly and continuously measure algal and toxin levels at
the point-of-need (PON), at a low cost. This review summarises the issues HABs
present, how they are difficult to monitor and recently developed biosensors that
may improve HAB-monitoring challenges.
PMID- 28427010
TI - Leveraging microbial biosynthetic pathways for the generation of 'drop-in'
biofuels.
AB - Advances in retooling microorganisms have enabled bioproduction of 'drop-in'
biofuels, fuels that are compatible with existing spark-ignition, compression
ignition, and gas-turbine engines. As the majority of petroleum consumption in
the United States consists of gasoline (47%), diesel fuel and heating oil (21%),
and jet fuel (8%), 'drop-in' biofuels that replace these petrochemical sources
are particularly attractive. In this review, we discuss the application of
aldehyde decarbonylases to produce gasoline substitutes from fatty acid products,
a recently crystallized reductase that could hydrogenate jet fuel precursors from
terpene synthases, and the exquisite control of polyketide synthases to produce
biofuels with desired physical properties (e.g., lower freezing points). With our
increased understanding of biosynthetic logic of metabolic pathways, we discuss
the unique advantages of fatty acid, terpene, and polyketide synthases for the
production of bio-based gasoline, diesel and jet fuel.
PMID- 28427012
TI - Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc
glycosylation.
AB - O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role
in modulating protein function in many cellular processes and human diseases such
as Alzheimer's disease and type II diabetes, and has emerged as a promising new
target. Specific inhibitors of OGT could be valuable tools to probe the
biological functions of O-GlcNAcylation, but a lack of robust nonradiometric
assay strategies to detect glycosylation, has impeded efforts to identify such
compounds. Here we have developed a novel label-free electrochemical biosensor
for the detection of peptide O-GlcNAcylation using protease-protection strategy
and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a
signal reporter. There is a large difference in the abilities of proteolysis of
the glycosylated and the unglycosylated peptides by protease, thus providing a
sensing mechanism for OGT activity. When the O-GlcNAcylation is achieved, the
glycosylated peptides cannot be cleaved by proteinase K and result in a high
current response on indium tin oxide (ITO) electrode. However, when the O
GlcNAcylation is successfully inhibited using a small molecule, the
unglycosylated peptides can be cleaved easily and lead to low current signal.
Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined
small-molecule OGT inhibitor. The results indicated that the biosensor could be
used to screen the OGT inhibitors effectively. Our label-free electrochemical
method is a promising candidate for protein glycosylation pathway research in
screening small-molecule inhibitors of OGT.
PMID- 28427013
TI - The accelerated path of ceritinib: Translating pre-clinical development into
clinical efficacy.
AB - The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung
cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK
inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance
to crizotinib invariably develops. There is now a next generation of ALK
inhibitors, including two that have been approved-ceritinib and alectinib-and
others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and
the other next-generation ALK inhibitors are more potent than crizotinib and can
overcome tumor cell resistance mechanisms. Ceritinib gained US Food and Drug
Administration approval in 2014 following accelerated review for the treatment of
patients with ALK-positive (ALK+) metastatic NSCLC who have progressed on or are
intolerant to crizotinib. In pre-clinical studies, it demonstrated more potent
inhibition of ALK than crizotinib in enzymatic assays, more durable responses in
xenograft models and the ability to potently overcome crizotinib resistance
mutations in vitro (including the gatekeeper mutation). There is also evidence
for ceritinib penetration across the blood-brain barrier. In clinical trials,
ceritinib has demonstrated durable responses and progression-free survival in ALK
inhibitor-pre-treated and -naive NSCLC patients, including high overall and
intracranial response rates in those with central nervous system metastases.
Selective gastrointestinal toxicity of ceritinib, such as diarrhea, nausea and
vomiting is generally manageable with prophylactic medication and prompt dose
reduction or interruption. Future progress in treating ALK+ NSCLC will focus on
determining the optimal sequencing of therapies and strategies to overcome
acquired resistance, an ongoing challenge in treating ALK-mutation-driven tumors.
PMID- 28427014
TI - Chemical and biological properties of a supramolecular complex of tuftsin and
cucurbit[7]uril.
AB - Cucurbit[7]uril (CB7) is an uncharged and water-soluble macrocyclic host. CB7
binds to doubly protonated tuftsin, which is the tetrapeptide Thr-Lys-Pro-Arg,
with moderate affinity (Ka=2.1*103M-1). In this study, the host-guest
complexation was confirmed by fluorescence titration. This affinity would allow
for easy release of the peptide under physiological conditions. According to
density functional theory calculations, the structural binding motif involves
hydrogen bonding. The most energetically stable form had the Arg side chain
inside the CB7 cavity. The effects of the tuftsin-CB7 complex on the
proliferation and cytokine activity of immune cells were studied. The complex had
broader spectrum immunomodulation than free peptides, and caused statistically
significant (p<0,05) changes in cytokine production (tumor necrosis factor-alpha,
interleukin-2, interferon-gamma, and interleukin-10) by mononuclear cells. By
contrast, the free peptide only activated tumor necrosis factor-alpha production.
PMID- 28427015
TI - Apparent anisotropy of adhesive bonds with weak adhesion and non-destructive
evaluation of interfacial properties.
AB - The present research attempts to non-destructively characterize mechanical
properties, which are representative of the interfacial adhesion and bond line
cohesion of adhesively bonded assemblies, using an ultrasonic method. Eight
bonded samples made of two aluminium substrates and of an epoxy-based adhesive
layer were manufactured: four in which the adhesive is fully cured (100%) and
four in which crosslinking is partial (80%). For each level of curing, four
different surface treatments were applied to the aluminium substrates before
assembling, in order to vary the quality of adhesion. Ultrasonic plane wave
transmission coefficients (UPWTC) were either measured in a water tank, or
simulated using the well-known stiffness matrix method that micmics the
experiments, to produce input data for the inverse problem. This latest consists
in the evaluation of the elastic properties of either the adhesive bond or the
interphases between both substrates and the adhesive layer. If the interphases
are of nominal quality, the values of the inferred properties of the adhesive
bond match those previously measured on individual epoxy samples, whether the
epoxy is fully or partially cured. However, when interphases are not of nominal
quality level, the optimized bond moduli reveal an apparent anisotropy, although
the epoxy layer is known to be isotropic. This apparent anisotropy is explained
by an analytical rule of mixture, thus giving confidence in the proposed
ultrasonic technique, which is then suggested as a potential way to detect
weaknesses of interphases. Finally, the optimization of the interphases elastic
properties is carried out. The measured normal and shear stiffnesses are shown to
decrease as the interphases get degraded. All ultrasonically-measured parameters
(apparent anisotropy of the bond and interfacial stiffnesses) vary monotonically
with the bonds strength, which was measured via mechanical tests. The proposed
UPWTC method was shown to have a strong potential to distinguish between adhesive
and cohesive weaknesses of bonded joints, and to estimate corresponding
mechanical properties.
PMID- 28427016
TI - Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers
and novel cinnamic ester derivatives.
AB - Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi
crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been
synthesized starting from d-glucose. The key step of the synthesis is a new one
pot sequence that commenced with a Z-selective Wittig olefination of suitably
functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)
triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the
corresponding 4-epimers (2 or 4, respectively). A number of 6-O-cinnamoyl
derivatives of styryl lactones 1-4 have been prepared, bearing electron donating
or electron withdrawing functionalities in the C-4 position of cinnamic acid
residue. The synthesized products were evaluated for their in vitro
antiproliferative activity against selected human tumour cell lines, whereupon
very potent cytotoxicities have been recorded in many cases. SAR analysis
indicated some important structural features responsible for biological activity,
such as stereochemistry at the C-4 and C-7 positions, as well as the nature of a
substituent at the C-4 position in the aromatic ring of cinnamoate moiety. Flow
cytometry and Western blot analysis data gave insight in the mechanism underlying
antiproliferative effects of the synthesized compounds.
PMID- 28427017
TI - Aromatase inhibitors and apoptotic inducers: Design, synthesis, anticancer
activity and molecular modeling studies of novel phenothiazine derivatives
carrying sulfonamide moiety as hybrid molecules.
AB - Hybrid molecules are used as anticancer agents to improve effectiveness and
diminish drug resistance. So, the current study aimed to introduce twenty novel
phenothiazine sulfonamide hybrids 5-22, 24 and 25 of promising anticancer
activity. Compounds 11 and 13 revealed more potent anticancer properties (IC50
8.1 and 8.8 MUM) than that of the reference drug (doxorubicin, IC50 = 9.8 MUM)
against human breast cancer cell line (T47D). To determine the mechanism of their
anticancer activity, compounds 5, 6, 7, 11, 13, 14, 16, 17, 19 and 22 that showed
promising activity on T47D, were evaluated for their aromatase inhibitory effect.
The study results disclose that the most potent aromatase inhibitors 11 and 13
showed the lowest IC50 (5.67 MUM and 6.7 MUM), respectively on the target enzyme.
Accordingly, the apoptotic effect of the most potent compound 11 was extensively
investigated and showed a marked increase in Bax level up to 55,000 folds, and
down-regulation in Bcl2 to 5.24*10-4 folds, in comparison to the control.
Furthermore, the effect of compound 11 on caspases 3, 8 and 9 was evaluated and
was found to increase their levels by 20, 34, and 8.9 folds, respectively, which
indicates the activation of both intrinsic and extrinsic pathways. Also, the
effect of compound 11 on the cell cycle and its cytotoxic effect were examined.
Moreover, a molecular docking and computer aided ADMET studies were adopted to
confirm their mechanism of action.
PMID- 28427018
TI - Left or right? Lateralizing temporal lobe epilepsy by dynamic amygdala fMRI.
AB - OBJECTIVES: In this case series, the findings of 85 functional MRI studies
employing a dynamic fearful face paradigm are reported. Previous findings have
shown the paradigm to generate bilateral amygdala activations in healthy subjects
and unilateral activations in patients with MTLE, in the contralateral hemisphere
to seizure origin. Such findings suggest ipsilateral limbic pathology and offer
collateral evidence in lateralizing MTLE. METHODS: The series includes 60
patients with TLE, 12 patients with extra-temporal lobe epilepsy, and 13 healthy
controls. Functional MRI studies using a 1.5T scanner were conducted over a three
year period at a single epilepsy center and individual results were compared with
EEG findings. RESULTS: In the cohort of unilateral TLE patients, lateralized
activations of the amygdala were concordant with EEG findings in 76% of patients
(77% lTLE, 74% rTLE). The differences in the mean lateralized indices of the
lTLE, rTLE, and healthy control groups were all statistically significant.
Lateralized amygdala activations were concordant with EEG findings in only 31% of
the 12 patients with extra-temporal lobe epilepsy and bilateral amygdala
activations were generated in all but one of the healthy control subjects.
SIGNIFICANCE: This case series further endorses the utility of the dynamic
fearful face functional MRI paradigm using the widely available 1.5T as an
adjunctive investigation to lateralize TLE.
PMID- 28427019
TI - Transplantation of inhibitory precursor cells from medial ganglionic eminence
produces distinct responses in two different models of acute seizure induction.
AB - Medial ganglionic eminence (MGE) is one of the sources of inhibitory interneurons
during development. Following transplantation in postnatal developing brain, MGE
cells can increase local inhibition suggesting a possible protection to GABAergic
dysfunction in brain disorders, such as epilepsy. Since it has been shown that
MGE-derived cells harvested as neurospheres are able to suppress seizures, it
might be important to investigate whether these protective effects would change
in different seizure models. Here, we used pentylenetetrazole-(PTZ) and maximal
electroshock (MES)-induced seizure models to test whether the transplantation of
MGE cells would increase the threshold to trigger acute seizures. When
transplanted into the neocortex (layers 3-4) of neonatal mice (postnatal days 3
4), MGE cells were able to survive and were mainly found in piriform cortex,
fimbria, and ventricular wall regions. Additionally, the number of GFP+ cells
found in the brains of mice induced with PTZ and MES differed significantly and
suggests proliferation and larger survival rate of MGE-transplanted cells after
PTZ, but not MES-induced seizures. Following transplantation, there was a
reduction in the number of animals presenting mild and severe seizures induced by
PTZ. Furthermore, MGE-cell transplantation was able to increase threshold to
seizures induced by PTZ, but was not able to prevent seizure spread induced by
MES.
PMID- 28427020
TI - Experiences with premorbid SUDEP discussion among participants in the North
American SUDEP Registry (NASR).
AB - The North American SUDEP Registry (NASR) is a repository of clinical data and
biospecimens in cases of sudden unexpected death in epilepsy (SUDEP), a leading
cause of epilepsy-related deaths. We assessed whether bereaved families were
aware of SUDEP before their family member's death and their preferences for SUDEP
disclosure. At enrollment, next-of-kin of SUDEP cases completed an intake
interview, including questions assessing premorbid SUDEP discussions. Only 18.1%
of the 138 next-of-kin recalled a previous discussion of SUDEP with a healthcare
provider or support resource. Of the 112 who did not recall such a discussion,
72.3% wished it was discussed, 10.7% were satisfied it was not discussed, and 17%
were unsure. A history of status epilepticus predicted SUDEP discussion. Rates of
SUDEP discussion were not significantly higher among SUDEPs after 2013 (the
approximate study midpoint) compared with those before then. Our study suggests
that SUDEP remains infrequently discussed with family members of persons with
epilepsy. Nearly three-quarters of family members wished they had known of SUDEP
before the death. However, some were indifferent or were satisfied that this
discussion had not occurred. We must balance more systematic education of
patients and families about SUDEP while respecting individual preferences about
having this discussion.
PMID- 28427021
TI - Risk factors for learning problems in youth with psychogenic non-epileptic
seizures.
AB - OBJECTIVES: This study examined the risk factors for learning problems (LP) in
pediatric psychogenic non-epileptic seizures (PNES) and their specificity by
comparing psychopathology, medical, cognitive/linguistic/achievement, bullying
history, and parent education variables between subjects with PNES with and
without LP and between subjects with PNES and siblings with LP. METHODS: 55
subjects with PNES and 35 siblings, aged 8-18years, underwent cognitive,
linguistic, and achievement testing, and completed somatization and anxiety
sensitivity questionnaires. A semi-structured psychiatric interview about the
child was administered to each subject and parent. Child self-report and/or
parent report provided information on the presence/absence of LP. Parents also
provided each subject's medical, psychiatric, family, and bullying history
information. RESULTS: Sixty percent (33/55) of the PNES and 49% (17/35) of the
sibling subjects had LP. A multivariable logistic regression demonstrated that
bullying and impaired formulation of a sentence using a stimulus picture and
stimulus word were significantly associated with increased likelihood of LP in
the PNES youth. In terms of the specificity of the LP risk factors, a similar
analysis comparing LP in the youth with PNES and sibling groups identified
anxiety disorder diagnoses and bullying as the significant risk factors
associated with LP in the PNES youth. CONCLUSIONS: These findings emphasize the
need to assess youth with PNES for LP, particularly if they have experienced
bullying, have linguistic deficits, and meet criteria for anxiety disorder
diagnoses.
PMID- 28427022
TI - Stereotypy of psychogenic nonepileptic seizures.
AB - Psychogenic nonepileptic seizures (PNES) are defined as paroxysmal episodes in
which epileptic semiology features are manifested, without the characteristic
concomitant electrical discharges seen in epileptic seizures. Although many
studies have dealt with semiologic classification of PNES, most of the studies
did not raise the question of consistency of PNES in the same patient. The aim of
this study was to measure the degree of consistency of PNES among individual
patients. We retrospectively reviewed medical records and video- EEG records of
all adult patients who underwent monitoring in our center from August 1st 2013 to
May 31st 2015. Those who were diagnosed with PNES with or without a background of
epilepsy were selected for this study. In order to check consistency between
seizures, we analyzed patients who had more than one recorded seizure during
monitoring. In case of more than 2 recorded seizures, the first two seizures were
analyzed. We found 53 patients who had PNES during this period, 29 of them had
more than one seizure. All seizures in the same patient were in the same
semiology category. In patients with either motor rhythmic or complex motor
seizures, we found a main anatomical region involved. The main anatomical region
involved was the same in 13 out of 14 patients. Movement frequency was highly
similar between the seizures of the same patient, while duration of seizures was
significantly different. Despite significant differences in duration between the
first and second seizure in patients with PNES, all other aspects tested were
highly similar. This shows that recurrent PNES in the same patient are
stereotypic. This supports the hypothesis that PNES is probably a dissociative
disorder.
PMID- 28427023
TI - The relationship between the Neuro-Quality of Life Depression and Anxiety
Measures and the Personality Assessment Inventory in persons with epilepsy.
AB - BACKGROUND: To investigate the associations between the Neuro-Quality of Life
(NQOL) Depression and Anxiety measures with an objective emotional inventory
(Personality Assessment Inventory; PAI), and demonstrate the clinical utility of
the NQOL as screening measures for depression and anxiety in persons with
epilepsy (PWE). METHODS: PWE (N=72) were concurrently administered the NQOL
Depression and Anxiety measures and the PAI. Pearson product moment correlations
were used to determine the relationships between the NQOL measures and the
respective PAI scales (i.e., depression, anxiety). One-way ANOVAs were conducted
comparing NQOL scores between patients with elevated levels of depression and
anxiety (T-score>=65 on the PAI) to profiles that were within normal limits.
Using sensitivity and specificity analyses, optimal cut-scores on the NQOL
measures were determined. RESULTS: Participants were primarily Caucasian (89%),
female (60%), and ~35 years old. The NQOL Depression measure was significantly
correlated with the PAI Depression total score (r=.747; p<0.001) and its
subscales (p's<0.001). Similarly, the NQOL Anxiety measure was significantly
correlated with the PAI Anxiety total score (r=.750; p<0.001) and its subscales
(p's<0.001). Compared to profiles that were within normal limits, individuals
with elevated depressive symptoms on the PAI had significantly higher NQOL
Depression scores (F(1,71)=48.2, p<0.001, d=1.6). Similarly, those who endorsed
elevated anxiety on the PAI had significantly higher NQOL Anxiety scores
(F(1,71)=32.2, p<0.001, d=1.5). Cut-off scores of 19 on the NQOL Depression and
24 on the NQOL Anxiety measures adequately detected depression (sensitivity=0.67;
specificity=0.93; PPV=0.91; NPV=0.74) and anxiety symptoms (sensitivity=0.77;
specificity=0.82; PPV=0.81; NPV=0.78) in PWE. CONCLUSIONS: The NQOL Depression
and Anxiety measures evidenced strong associations with the PAI Depression and
Anxiety scales and may be effective in detecting depressive and anxiety symptoms
in PWE using the provided cut-scores.
PMID- 28427024
TI - Knowledge, attitude, and practice about epilepsy among teachers at Ethio-National
School, Addis Ababa, Ethiopia.
AB - BACKGROUND: Epilepsy is one of the most common serious chronic brain disorders
and is poorly understood by the public and has been associated with numerous
misconceptions and beliefs. This, coupled with its dramatic clinical
manifestations, has resulted in a strong social stigma. Since teachers have a key
role in society as educators, the purpose of this study was to find out the
knowledge, attitude, and practice towards epilepsy among school teachers.
METHODS: A cross-sectional study design was used to assess the knowledge,
attitude, and practice of 135 teachers about epilepsy using a semi-structured,
self-administered questionnaire. Data were entered into IBM SPSS version 20.0 and
analyzed. Descriptive statistics including frequencies, means, and standard
deviations were used to describe the data. Associations were computed using a chi
square test and p-value<0.05 was considered significant. RESULTS: Nearly all
teachers 122 (96.3 %) were aware of epilepsy. Only 41% of the respondents had
good knowledge about epilepsy whereas 26.8% and 32.3% had fair and poor knowledge
about the disease, respectively. About 74% of them had a positive attitude about
epilepsy. Only 60.3% of the respondents had proper first aid training. Literacy
status and years of experience were not significantly associated with the level
of knowledge about epilepsy. CONCLUSION: A significant proportion of teachers had
deficits in terms of general knowledge, attitude, and the appropriate management
of epilepsy in the classroom. Therefore, it is important to train and update
teachers on epilepsy by the responsible health authorities.
PMID- 28427025
TI - Psychiatric symptoms after temporal epilepsy surgery. A one-year follow-up study.
AB - Psychiatric symptoms must be considered in patients with refractory temporal lobe
epilepsy after epilepsy surgery. The main objectives of our study were to
describe clinical and socio-demographical characteristics of a cohort of patients
with pharmacoresistant temporal lobe epilepsy who underwent temporal lobe
epilepsy surgery, and moreover, to evaluate possible risk factors for developing
psychiatric symptoms. In order to achieve those goals, we conducted a prospective
evaluation of psychopathology throughout the first year after surgery in a
clinical sample of 72 patients, by means of three clinical rated measures; the
Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale
(HDRS), and the Brief Psychiatric Rating Scale (BPRS). The psychopathological
evaluations were performed by an experienced psychiatrist. A presurgical
evaluation was done by a multidisciplinary team (that includes neurologist,
psychiatrist, neurosurgeon, neurophysiologist, radiologists, and nuclear medicine
specialist) in all patients. The decision to proceed to surgery was taken after a
surgical meeting of all members of the Multidisciplinary Epilepsy Unit team. The
psychiatrist conducted two postoperative assessments at 6months and 12months
after surgery. The main finding was that past history of mental illness (patients
who were receiving psychiatric treatment prior to the baseline evaluation) was a
risk factor for anxiety, depression, and psychosis after temporal lobe epilepsy
surgery.
PMID- 28427026
TI - Epilepsy and headaches: Further evidence of a link.
AB - OBJECTIVE: Epilepsy and primary headaches are two of the most common neurologic
conditions that share some common clinical characteristics, and can affect
individuals of all age groups around the world. In recent years, the underlying
pathophysiologic mechanisms potentially common to both headaches and epileptic
seizures have been the subject of scrutiny. The objective of this study was to
determine the frequencies and types of headaches in patients with epilepsy, and
evaluate any temporal relationship with epileptic seizures. METHOD: Demographic
data, epilepsy durations, seizure frequencies, seizure types and antiepileptic
medications used were captured of 349 patients who were followed up at our
epilepsy outpatient clinic. Patients who experienced headaches were grouped based
on the type of headaches and on whether their headaches occurred in the preictal,
postictal or interictal period. RESULT: Three hundred forty-nine patients (190
females, 159 males) were enrolled in the study. The patients' average age was
30.9+/-13.1 years, and average epilepsy duration was 13.5+/-10.9 years. The types
of epileptic seizures were partial in 19.8% of patients, generalized in 57.9%,
and secondary generalized in 20.3% of patients. Some 43.6% of the patients did
not experience headaches, and 26.9% had migraine and 17.2% tension-type
headaches. Headaches could not be classified in 12.3% of patients. The headaches
occurred preictally in 9.6%, postictally in 41.6% and interictally in 8.6% of
patients. The ratio of headaches was lower in male patients compared with
females, and females experienced migraine-type headaches more frequently compared
with males (p=0.006). Migraine-type headaches were less frequent a mong patients
who experienced less than one seizure per year, but more frequent (p=0.017) among
those who experienced more than one seizure per month, but less than one seizure
per week. Migraine-type headaches were significantly more frequent (p=0.015)
among patients receiving polytherapy compared with patients receiving
monotherapy. CONCLUSION: The results of this study suggest that headaches,
particularly migraine-type headaches, were frequently experienced by patients
with epilepsy, postictal headaches were more common, and the frequency of
migraine attacks could be linked with seizure frequency and the type of
treatment.
PMID- 28427027
TI - Multisensory temporal function and EEG complexity in patients with epilepsy and
psychogenic nonepileptic events.
AB - Cognitive and perceptual comorbidities frequently accompany epilepsy and
psychogenic nonepileptic events (PNEE). However, and despite the fact that
perceptual function is built upon a multisensory foundation, little knowledge
exists concerning multisensory function in these populations. Here, we
characterized facets of multisensory processing abilities in patients with
epilepsy and PNEE, and probed the relationship between individual resting-state
EEG complexity and these psychophysical measures in each patient. We
prospectively studied a cohort of patients with epilepsy (N=18) and PNEE (N=20)
patients who were admitted to Vanderbilt's Epilepsy Monitoring Unit (EMU) and
weaned off of anticonvulsant drugs. Unaffected age-matched persons staying with
the patients in the EMU (N=15) were also recruited as controls. All participants
performed two tests of multisensory function: an audio-visual simultaneity
judgment and an audio-visual redundant target task. Further, in the cohort of
patients with epilepsy and PNEE we quantified resting state EEG gamma power and
complexity. Compared with both patients with epilepsy and control subjects,
patients with PNEE exhibited significantly poorer acuity in audiovisual temporal
function as evidenced in significantly larger temporal binding windows (i.e.,
they perceived larger stimulus asynchronies as being presented simultaneously).
These differences appeared to be specific for temporal function, as there was no
difference among the three groups in a non-temporally based measure of
multisensory function - the redundant target task. Further, patients with PNEE
exhibited more complex resting state EEG patterns as compared to their patients
with epilepsy, and EEG complexity correlated with multisensory temporal
performance on a subject-by-subject manner. Taken together, findings seem to
indicate that patients with PNEE bind information from audition and vision over
larger temporal intervals when compared with control subjects as well as patients
with epilepsy. This difference in multisensory function appears to be specific to
the temporal domain, and may be a contributing factor to the behavioral and
perceptual alterations seen in this population.
PMID- 28427028
TI - Terminal seizure frequency and its relation to SUDEP.
AB - BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a major cause of death
in patients with epilepsy. Several risk factors have been implicated, including
early age of onset, tonic-clonic seizures and antiepileptic drugs. However,
whether patients who die from SUDEP have a greater frequency of seizures in the
few months before death is unclear. We investigated the terminal seizure
frequency and its relation to SUDEP among a large group of patients with tonic
clonic seizures in rural West China. METHODS: We used the database from the
Convulsive Epilepsy Control and Management Program in West China, which routinely
provides phenobarbital (PB) as a treatment for convulsive epilepsy. Patients with
probable SUDEP were included according to pre-set criteria. A verbal autopsy was
undertaken for each case. By matching each patient's age, sex, date of joining
the program, time in follow-up, and baseline seizure frequency, we set up a 1:5
ratio control group. SPSS 21.0 statistics were applied to compare the differences
in seizure frequency 3months prior to SUDEP between patients with probable SUDEP
and controls. Furthermore, the dynamic changes of terminal seizure frequency 6
9months, 3-6months, and 3months prior to SUDEP was also analyzed. RESULTS: A
total of 41 patients who died from probable SUDEP were identified out of 7844
patients during 10years of follow-up. The SUDEP group had a significantly higher
tonic-clonic seizure frequency 3months before their deaths than the control group
(p=0.023). At the same time, their seizure-free rate was lower than the control
group (p=0.025). Patients with probable SUDEP who were followed up over 12months
were further studied as a subgroup. They had more tonic-clonic seizures 3months
prior to death compared to the control group (p=0.010). They also had an increase
in seizure frequency in their terminal phase (3months prior) compared to an
earlier stage (3-6months prior) (p=0.029). Furthermore, the terminal PB dose in
the SUDEP group was higher than the control group (p=0.002). CONCLUSION: Patients
who died from SUDEP had more frequent tonic-clonic seizures 3months before their
deaths. Higher seizure frequency increases the exposure to peri-ictal
pathophysiological events, which possibly relate to SUDEP. This phenomenon may be
due to the drug resistance potential of these patients or the high dose of PB.
Further research is required to ascertain the underlying mechanisms of SUDEP.
PMID- 28427029
TI - Treatment of refractory and super-refractory status epilepticus with
brivaracetam: A cohort study from two German university hospitals.
AB - PURPOSE: We aimed to ascertain the possible use of brivaracetam (BRV) as an
option for treatment of status epilepticus (SE). METHODS: A review of medical
records was carried out to detect BRV administration in SE patients treated in
Frankfurt and Greifswald during the period February 2016 to January 2017. The
primary outcome question concerned SE resolution after BRV initiation. RESULTS:
During that period, BRV was started with eleven adult patients with SE. Five of
these were female, and the median age was 64 (interquartile range [IQR] 21years).
The median SE duration before BRV initiation was 5days (IQR 9days); the median
number of previous anticonvulsants used was 4 (IQR 5). Initial BRV doses ranged
between 50mg and 400mg (median 100mg), titrated to a daily dose of 100 to 400mg
(median 200mg). There was a cessation of SE in the first 24h of BRV in three
patients (27%). While taking BRV, no serious side effects were seen. CONCLUSION:
Based on these cases and previous data from animal experiments, BRV may prove
useful in SE treatment, and trials would be warranted to examine BRV's efficacy
in treating SE and how this efficacy might be influenced by co-administration
with levetiracetam.
PMID- 28427030
TI - The relationship between sign production and sign comprehension: What handedness
reveals.
AB - Unlike the phonological loop in spoken language monitoring, sign language users'
own production provides mostly proprioceptive feedback and only minimal visual
feedback. Here we investigate whether sign production influences sign
comprehension by exploiting hand dominance in a picture-sign matching task
performed by left-handed signers and right-handed signers. Should all signers
perform better to right-handed input, this would suggest that a frequency effect
in sign perception drives comprehension. However, if signers perform better to
congruent-handed input, this would implicate the production system's role in
comprehension. We found evidence for both hypotheses, with variation dependent on
sign type. All signers performed faster to right-handers for phonologically
simple, one-handed signs. However, left-handed signers preferred congruent-handed
input for phonologically complex, two-handed asymmetrical signs. These results
are in line with a weak version of the motor theory of speech perception, where
the motor system is only engaged when comprehending complex input.
PMID- 28427031
TI - Executive function depletion in children and its impact on theory of mind.
AB - The current studies provide an experimental, rather than correlational, method
for testing hypotheses about the role of executive function (EF) in conceptual
development. Previous research has established that adults' tendency to deploy EF
can be temporarily diminished by use. Exercising self-control in one context
decreases adults' performance on other EF demanding tasks immediately thereafter.
Using two different depletion methods, Experiments 1 and 3 extend this finding to
preschool-aged children. Experiments 2 and 4 make use of these EF depletion
methods to elucidate the role of EF in children's theory of mind reasoning.
Experiment 2 shows that EF depletion affects 5-year-olds' ability to predict
another's behavior on the basis of that person's false belief, and Experiment 4
shows that this negative effect of depletion extends to 4- and 5-year-olds'
ability to explain others' behavior on the basis of their false beliefs. These
findings provide direct evidence that EF is required for the expression of an
understanding of others' false beliefs across a variety of task demands, even in
children who clearly have the capacity to construct such representations. We
suggest ways in which depletion may be used as a tool for further investigating
the role of executive function in cognitive development.
PMID- 28427032
TI - Social cognition in bipolar disorder: Focus on emotional intelligence.
AB - BACKGROUND: The present study aims to characterize emotional intelligence (EI)
variability in a sample of euthymic bipolar disorder (BD) patients through the
Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT). METHOD: A total of
134 euthymic BD outpatients were recruited and divided into three groups
according to the total Emotional Intelligence Quotient (EIQ) score of the MSCEIT,
following a statistical criterion of scores 1.5SDs above/below the normative
group mean, as follows: a low performance (LP) group (EIQ <85), a normal
performance (NP) group (85<=EIQ<=115), and a high performance (HP) group (EIQ
>115). Afterwards, main sociodemographic, clinical, functional and neurocognitive
variables were compared between the groups. RESULTS: Three groups were
identified: 1) LP group (n=16, 12%), 2) NP group (n=93, 69%) and 3) HP group
(n=25, 19%). There were significant differences between the groups in premorbid
intelligence quotient (IQ) (p=0.010), axis II comorbidity (p=0.008), subthreshold
depressive symptoms (p=0.027), general functioning (p=0.013) and in four specific
functional domains: autonomy, occupation, interpersonal relations and leisure
time. Significant differences in neurocognitive performance were found between
groups with the LP group showing the lowest attainments. LIMITATIONS: The cross
sectional design of the study. CONCLUSION: Our results suggest that EI
variability among BD patients, assessed through MSCEIT, is lower than expected.
EI could be associated with premorbid IQ, subthreshold depressive symptoms,
neurocognitive performance and general functioning. The identification of
different profiles of SC may help guide specific interventions for distinct
patient subgroups aimed at improving social cognition, neurocognitive performance
and psychosocial functioning.
PMID- 28427033
TI - Toxicity of sulfadiazine and copper and their interaction to wheat (Triticum
aestivum L.) seedlings.
AB - A pot experiment was carried out to investigate the single and combined effect of
different concentrations of sulfadiazine (SDZ) (1 and 10mgkg-1) and copper (Cu)
(20 and 200mgkg-1) stresses on growth, hydrogen peroxide (H2O2), malondialdehyde
(MDA), antioxidant enzyme activities of wheat seedlings and their accumulation.
High SDZ or Cu level significantly inhibited the growth of wheat seedlings, but
the emergence rate was only inhibited by high SDZ level. The presence of Cu
reduced the accumulation of SDZ, whereas the effect of SDZ on the accumulation of
Cu depended on their concentrations. Low Cu level significantly increased the
chlorophyll content, while high Cu level or both SDZ concentrations resulted in a
significant decrease in the chlorophyll content as compared to the control.
Additionally, H2O2 and MDA contents increased with the elevated SDZ or Cu level.
The activities of superoxide dismutase, peroxidase and catalase were also
stimulated by SDZ or Cu except for the aerial part treated by low Cu level and
root treated by high SDZ level. The joint toxicity data showed that the toxicity
of SDZ to wheat seedlings was generally alleviated by the presence of Cu, whereas
the combined toxicity of SDZ and Cu was larger than equivalent Cu alone.
PMID- 28427034
TI - Taxometric analyses and predictive accuracy of callous-unemotional traits
regarding quality of life and behavior problems in non-conduct disorder
diagnoses.
AB - Callous-unemotional (CU) traits have mainly been studied in relation to conduct
disorder (CD), but can also occur in other disorder groups. However, it is
unclear whether there is a clinically relevant cut-off value of levels of CU
traits in predicting reduced quality of life (QoL) and clinical symptoms, and
whether CU traits better fit a categorical (taxonic) or dimensional model.
Parents of 979 youths referred to a child and adolescent psychiatric clinic rated
their child's CU traits on the Inventory of Callous-Unemotional traits (ICU), QoL
on the Kidscreen-27, and clinical symptoms on the Child Behavior Checklist.
Experienced clinicians conferred DSM-IV-TR diagnoses of ADHD, ASD, anxiety/mood
disorders and DBD-NOS/ODD. The ICU was also used to score the DSM-5 specifier
'with limited prosocial emotions' (LPE) of Conduct Disorder. Receiver operating
characteristic (ROC) analyses revealed that the predictive accuracy of the ICU
and LPE regarding QoL and clinical symptoms was poor to fair, and similar across
diagnoses. A clinical cut-off point could not be defined. Taxometric analyses
suggested that callous-unemotional traits on the ICU best reflect a dimension
rather than taxon. More research is needed on the impact of CU traits on the
functional adaptation, course, and response to treatment of non-CD conditions.
PMID- 28427035
TI - Associations between executive functions and mental health outcomes for adults
with autism spectrum disorder.
AB - Associations between executive functions (EF) and mental-health in adults with
autism spectrum disorder (ASD) were examined. Forty-two adults with ASD completed
measures of EF, mood and self-concept. Better concept formation and social
inference skills were significantly associated with fewer anxiety symptoms.
Conversely, participants with better non-verbal reasoning, cognitive flexibility
and social cognition reported more negative self-concept and lower self-esteem.
Overall, individuals with impaired EF are more prone to anxiety, whereas those
with stronger EF are more likely to experience negative self-concept. Screening
for and monitoring mental-health concerns in people with ASD regardless of their
level of EF is recommended.
PMID- 28427036
TI - The dose-dependent effect of zearalenone on mitochondrial metabolism, plasma
membrane permeabilization and cell cycle in human prostate cancer cell lines.
AB - Zearalenone (ZEA) is a nonsteroidal mycotoxin produced by several fungi of the
genus Fusarium spp. It is known to play various roles in the regulation of the
prostate cancer cell cycle, including carcinogenesis. The present study evaluates
the influence of ZEA on the mitochondrial metabolism, plasma membrane
permeabilization and cell cycle of prostate cancer cells. At concentrations of
100 nM and 0.3 nM, ZEA caused a decrease in the oxidative activity of
mitochondria, as well as increases in LDH release, apoptosis induction and the
number of cells in the G0/G1 phase. The opposite effect was observed for lower
concentrations (0.1 nM and 0.001 nM). These in vitro studies indicate that ZEA
might have pro- and antiproliferative properties in prostate cancer cells, at
concentrations 0.1 nM, 0.001 nM and 0.3 nM, 100 nM, respectively.
PMID- 28427037
TI - Monitoring of styrene oligomers as indicators of polystyrene plastic pollution in
the North-West Pacific Ocean.
AB - Styrene oligomers (SOs) as global contaminants are an environmental concern.
However, little is known on the distribution of SOs in the ocean. Here, we show
the distribution of anthropogenic SOs generated from discarded polystyrene (PS)
plastic monitored from the coastal ocean surface waters (horizontal distribution)
and deep seawaters (vertical distribution) in the North-West Pacific Ocean. SOs
concentrations in surface seawater and deep seawater ranged from 0.17 to 4.26 MUg
L-1 (total mean: 1.48 +/- 1.23 MUg L-1) and from 0.31 to 4.31 MUg L-1 (total
mean: 1.32 +/- 0.87 MUg L-1), respectively. Since there is no significant
difference in the mean concentrations, SOs seems to be spread across marine
environment selected in this study. Nevertheless, regional SOs appears to persist
to varying degrees with their broad horizontal and vertical distribution in the
ocean. Each horizontal and vertical distribution of SOs differs by approximately
1.95-2.57 times, probably depending on the events of weather and global ocean
circulation. These results provide the distribution pattern of SOs for assessing
environmental pollution arising from PS plastic.
PMID- 28427038
TI - Urinary triclosan concentrations during pregnancy and birth outcomes.
AB - BACKGROUND: Triclosan is an antimicrobial chemical used in consumer products, and
exposure is ubiquitous among pregnant women in the United States. Triclosan may
reduce the levels of thyroid hormones that are important for fetal growth and
development. OBJECTIVE: We investigated the relationship of prenatal triclosan
exposure with birth anthropometry and gestational duration. METHODS: We used data
from 378 mother-child pairs participating in the Health Outcomes and Measures of
the Environment (HOME) Study, a prospective pregnancy and birth cohort from
Cincinnati, OH. We measured triclosan concentrations in maternal urine samples
collected at 16 and 26 weeks of pregnancy. We abstracted information on neonatal
anthropometry and gestational duration from medical records. We used
multivariable linear regression to estimate the covariate-adjusted association
between the average of the two urinary triclosan concentrations and gestational
age standardized weight z-score, length, head circumference, and gestational age
at birth. RESULTS: Median urinary triclosan concentrations were 16ng/mL (range:
<2.4 to 1501ng/mL). Each 10-fold increase in triclosan was associated with a
predicted 0.15 standard deviation decrease (95% CI: -0.30, 0.00) in birth weight
z-score, 0.4-cm decrease (95% CI: -0.8, 0.1) in birth length, 0.3-cm decrease
(95% CI: -0.5, 0.0) in head circumference, and 0.3-week decrease (95% CI: -0.6,
0.1) in gestational age. Child sex did not modify the associations between
triclosan and birth outcomes. CONCLUSIONS: In this cohort, maternal urinary
triclosan concentrations during pregnancy were inversely associated with infants'
birth weight, length, head circumference, and gestational age.
PMID- 28427039
TI - Low dose growth hormone treatment in infants and toddlers with Prader-Willi
syndrome is comparable to higher dosage regimens.
AB - OBJECTIVE: Evaluate benefit and risk of low dose growth hormone treatment (GHT,
4.5mg/m2/week) in very young children with Prader-Willi Syndrome (PWS). DESIGN:
Prospective longitudinal clinical intervention. METHODS: We evaluated 31 infants
(aged 2-12months) and 42 toddlers (13-24months) from the PWS-OZGROW database for
height, weight and BMI using the World Health Organization standard deviation
scores (SDSWHO) and PWS specific BMI (SDSPWS), bone age, insulin-like growth
factor 1 (IGF-I) levels and adverse events over 3years of GHT. RESULTS: At
commencement of GHT infants had a lower BMI SDSWHO (-0.88 vs 0.40) than toddlers,
while toddlers had a lower height SDSWHO (-1.44 vs -2.09) (both P<0.05). All
increased height SDSWHO (2year delta height infants +1.26 SDS, toddlers+1.21
SDS), but infants normalised height sooner, achieving a height SDS of -0.56
within 1year, while toddlers achieved a height SDS of -0.88 in two years. BMI
SDSWHO increased, while BMI SDSPWS decreased (both P<0.0001) and remained
negative. The GHT response did not differ with gestation (preterm 23%) or genetic
subtype (deletion vs maternal uniparental disomy). Bone age advancement
paralleled chronological age. All children had low serum IGF-I at baseline which
increased, but remained within the age-based reference range during GHT (for 81%
in first year). Four children had spinal curvature at baseline; two improved, two
progressed to a brace and two developed an abnormal curve over the observation
period. Mild to severe central and/or obstructive sleep apnoea were observed in
40% of children prior to GHT initiation; 11% commenced GHT on positive airway
pressure (PAP), oxygen or both. Eight children ceased GHT due to onset or
worsening of sleep apnoea: 2 infants in the first few months and 6 children after
6-24months. Seven resumed GHT usually after adjusting PAP but five had
adenotonsillectomy. One child ceased GHT temporarily due to respiratory illness.
No other adverse events were reported. Two children substantially improved their
breathing shortly after GHT initiation. CONCLUSION: Initiation of GHT in infants
with 4.5mg/m2/week was beneficial and comparable in terms of auxological response
to a dose of 7mg/m2/week. Regular monitoring pre and post GH initiation assisted
in early detection of adverse events. IGF-I levels increased with the lower dose
but not excessively, which may lower potential long-term risks.
PMID- 28427040
TI - Cortex Mori Radicis extract attenuates myocardial damages in diabetic rats by
regulating ERS.
AB - Diabetic cardiomyopathy (DCM) is diagnosed when patients with diabetes develop
ventricular dysfunction but do not exhibit coronary atherosclerosis or
hypertension. Cortex Mori (CM) Radicis,he epidermis of the root of Morus alba L,
has been traditionally used for cough treatment in oriental medicine. In this
study, we investigated the protection of myocardium by CM in streptozotocin (STZ)
induced diabetic rats and the underlying mechanisms. Diabetes was induced in rats
by an injection of STZ at 25mg/kg. The animals were randomly divided into 4
groups: control, diabetes, diabetes with CM treatment, diabetes with CM
preventative treatment. Pathological changes were examined by hematoxylin-eosin
staining. Extracellular matrix content was assessed by Masson's trichrome
staining and Western blot. Endoplasmic reticulum (ER) stress-associated molecules
and main components of the mitogen-activated protein kinase (MAPK) pathway were
also measured by Western blot. Myocardial damages were induced by the injection
of STZ as evidenced by abnormal blood glucose and pathological cardiac changes.
Administration of CM markedly ameliorated myocardial damages such as cardiac
hypertrophy and fibrosis. ER stress was down-regulated, and p38 and ERK were
suppressed by CM. Thus, CM may have therapeutic potential in the treatment of DCM
by attenuating ER stress and ERK and p38 MAPK activation.
PMID- 28427042
TI - Long-term performance assessment of HPGE detectors used in the neutron activation
analysis laboratory of IPEN-CNEN/SP (Brazil).
AB - In this work, verification data for 11 HPGe detectors from two different
manufacturers and three different intrinsic configurations were analyzed in
respect to the stability of both the efficiency and resolution for the 122keV
peak from 57Co and the 1332keV peak from 60Co. The results allow a discussion
about the stability of these parameters over time (in some cases, almost 15
years), their sensitivity to imminent detector failures and their performance
after a failure has been corrected; moreover, the results show a clear
correlation between the manufacturer or configuration and the long-term
performance of the detector.
PMID- 28427041
TI - The efficacy of donepezil administration on acetylcholinesterase activity and
altered redox homeostasis in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a serious multifactorial disorder with progressive
neurodegenerative outcomes related with impaired redox homeostasis. Inhibition of
the enzyme acetylcholinesterase (AChE), as one of the major therapeutic
strategies, is considered to be offering only symptomatic relief and moderate
disease modifying effect. We intended to investigate the effects of
acetylcholinesterase inhibition via donepezil on protein carbonyl (PCO), advanced
protein oxidation products (AOPP) and ischemia modified albumin (IMA) as protein
oxidation markers and ferric reducing antioxidant power (FRAP), prooxidant
antioxidant balance (PAB), total thiol (T-SH), protein thiol (P-SH) as
antioxidant status markers and also kynurenine (KYN), N-formyl kynurenine (N
FKYN) and protein bound dityrosine (DT) levels all in one demonstrating the redox
homeostasis in Alzheimer patients also correlated with AChE activity. The AChE
activity and PCO, KYN, N-FKYN and DT levels were found to be significantly higher
in the AD group than the control group. The FRAP, T-SH and P-SH levels were
significantly lower in the AD group than in the control group. The AChE activity
was significantly higher both in donepezil treated and untreated groups when
compared with the control group. PCO levels were significantly higher in
Alzheimer's untreated group than the healthy control and donepezil treated
groups. AChE activity was positively correlated with PCO, IMA, PAB, KYN and N
FKYN levels and negatively correlated with FRAP, T-SH and P-SH levels in all
participants. Our data showed that treatment with donepezil had ameliorating
effects on redox homeostasis in Alzheimer patients. AChE inhibition seems to be
exhibiting a potent antioxidant role and may inhibit protein oxidation by
decreasing AChE activity in AD, thus medicinal natural substances exhibiting the
similar mechanism of action with their antioxidant behaviours can be recommended
for the emphasis on new drug new drug development. Further clinical and
experimental studies are needed to support our current findings and conclusions.
PMID- 28427043
TI - Neutron radiation shielding properties of polymer incorporated self compacting
concrete mixes.
AB - In this work, the neutron radiation shielding characteristics of a class of novel
polymer-incorporated self-compacting concrete (PISCC) mixes are evaluated.
Pulverized high density polyethylene (HDPE) material was used, at three different
reference volumes, as a partial replacement to river sand in conventional
concrete mixes. By such partial replacement of sand with polymer, additional
hydrogen contents are incorporated in these concrete mixes and their effect on
the neutron radiation shielding properties are studied. It has been observed from
the initial set of experiments that there is a definite trend of reductions in
the neutron flux and dose transmission factor values in these PISCC mixes vis-a
vis ordinary concrete mix. Also, the fact that quite similar enhanced shielding
results are recorded even when reprocessed HDPE material is used in lieu of the
virgin HDPE attracts further attention.
PMID- 28427044
TI - On the reverse micelle effect in liquid scintillation counting.
AB - This work looks into the tracks of electrons in nanoemulsive scintillating media
using the Monte Carlo Geant4-DNA code which simulates event-by-event interactions
of electrons in liquid water down to the eV, without resorting to the condensed
history method. It demonstrates that the average number of micelles in which
electrons deposit energy is quite large, increasing with their emission energy,
decreasing with micelle size, and rising with micelle concentration. The
probability of an electron ending its track in a micelle is found to be rather
large and micelle size-dependent below 1keV, and approximating the aqueous
fraction at higher energies. Analyses of the Monte Carlo estimated energy
depositions in the aqueous phase and in the scintillant tell of a micelle
quenching effect, with the micelle size shaping the quenching at low energy and
the micelle concentration governing it at higher energies. The micelle effect on
the 3H and 63Ni beta spectra is discussed for a range of micelle sizes and
concentrations. This paper also computes the ionisation quenching function using
Birk's law whilst considering the full energy losses in the micelles bisecting
the electron pathway, and not just that incurred in the primary micelle enclosing
the decaying nuclide. The ionisation quenching function is then used to calculate
the detection efficiencies for 3H, 63Ni, 54Mn and 55Fe. The effect of the micelle
size is found to be small for beta emitters but significant for the electron
capture nuclides. TDCR measurements of 63Ni samples covering 8 aqueous fractions
are analysed with and without explicit treatment of the micelle effect.
Activities in the two representations agree within 0.02%. The ratios of the
corresponding figures of merit are found to coincide with the scintillant
fractions.
PMID- 28427045
TI - MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting
HMGB1-Mediated Autophagy.
AB - BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high
mortality rate. Drug resistance represents a main obstacle in NSCLC treatment.
High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells
by activating protective autophagy. METHODS: In the current study, we
investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1
mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in
vitro and in vivo. HMGB1 was identified as a putative target gene of miR-142-3p
by in silico analysis. Our luciferase reporter assay results confirmed that miR
142-3p directly targets the 3'-UTR of HMGB1 in NSCLC cells. RESULTS: MiR-142-3p
overexpression suppressed while miR-142-3p knockdown increased HMGB1 mRNA and
protein expression. Starvation induced HMGB1 expression and activated autophagy
in NSCLC cells. The starvation-induced autophagy was inhibited by miR-142-3p
overexpression or HMGB1 knockdown. Moreover, miR-142-3p overexpression or HMGB1
knockdown increased PI3K, Akt, and mTOR phosphorylation. Inhibition of PI3K or
mTOR restored starvation-induced autophagy inhibited by miR-142-3p overexpression
or HMGB1 knockdown. CONCLUSIONS: These results demonstrated that miR-142-3p
regulates starvation-induced autophagy of NSCLC cells by directly downregulating
HMGB1 and subsequently activating the PI3K/Akt/mTOR pathway. Further, miR-142-3p
overexpression inhibited anticancer drug-induced autophagy and increased chemo
sensitivity of NSCLC in vitro and in vivo. These findings shed light on the
therapeutic potential of miR-142-3p in combating acquired NSCLC chemo-resistance.
PMID- 28427046
TI - Impressive Response to Pixantrone after Allogeneic Transplant in a Multiple
Relapsed Diffuse Large B-Cell Lymphoma.
AB - Diffuse large B-cell lymphoma is the most frequent histology at diagnosis among
non-Hodgkin B lymphomas and can be cured in 50-70% of cases after the first-line
chemotherapy regimen. Patients who do not respond to first-line treatment can
undergo numerous subsequent steps, culminating in allogeneic stem cell transplant
(alloSCT). A relapse after alloSCT, however, carries an awful prognosis, seeing
the demise of the patient usually in the following months. Here we present the
case of a multiple relapsed patient who successfully underwent therapy with
pixantrone after alloSCT, obtaining a complete remission without any considerable
side effects.
PMID- 28427047
TI - Co-Activation of TGFbeta and Wnt Signalling Pathways Abrogates EMT in Ovarian
Cancer Cells.
AB - BACKGROUND/AIMS: The aggressive property of ovarian cancer (OC) in terms of
epithelial-mesenchymal transition (EMT), proliferation and metastasis are of
major concern. Different growth factors including TGFbeta are associated with
regulating these molecular events but the underlying mechanisms remain unclear.
The aim of this report is to decipher the regulation of EMT by co-activation of
TGFbeta and Wnt signalling cascades in gaining malignancy. METHODS: The
expression of the different components of signalling events were analyzed by
QPCR, Western blot, Immunofluorescence microscopy and flow cytometry. beta
catenin promoter activity was checked by luciferase assay. RESULTS: We observed
reduced EMT in ovarian cancer cells upon co-activation with TGFbeta1 and LiCl as
shown by the expressions of epithelial/mesenchymal markers and the EMT promoting
factor, Snail1, accompanied by decrease in the invasion and migration of the
cells compared to individual pathway activation. A detailed study of the
mechanism suggested reduction in the beta-catenin and p-GSK3b (Ser 9) levels to
be the driving cause of this phenomenon, which was reversed upon co-activation
with higher concentrations of LiCl. CONCLUSIONS: Therefore, tumourigenesis might
be affected by the concentration of ligand/ growth factors for the respective
signalling pathways activated in the tumour microenvironment and interaction
between them might alter tumourigenesis.
PMID- 28427048
TI - 1,25-Dihydroxyvitamin D3 Attenuates the Effects of Lipopolysaccharide by Causing
ADAM10-Dependent Ectodomain Shedding of Toll-Like Receptor 4.
AB - BACKGROUND/AIMS: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits
the effects of lipopolysaccharide (LPS) in human aortic endothelial cells.
METHODS: Cellular signaling was explored by determination of protein abundance
with Western blot, measurement of cytosolic Ca2+ concentration and
immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10).
RESULTS: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM
1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen
activated protein kinase (p38 MAPK). Pretreatment with 1,25D3 attenuated LPS
induced p38 MAPK activation and ICAM-1 expression by causing ectodomain shedding
of TLR4. This effect of 1,25D3 depended on its ability to induce a rapid
extracellular Ca2+ influx through L-type calcium channels because the ectodomain
shedding was prevented by the absence of extracellular Ca2+ or the presence of
verapamil. TLR4 ectodomain shedding was also induced by Bay K8644 (L-type calcium
channel agonist). Both 1,25D3 and Bay K8644 caused extracellular Ca2+ influx
dependent ADAM10 translocation to the cell surface. Depletion of ADAM10 by siRNA
transfection prevented 1,25D3- and Bay K8644-induced ectodomain shedding of TLR4,
and abolished the inhibitory effect of 1,25D3 on LPS-induced ICAM-1 expression.
CONCLUSION: 1,25D3 causes ectodomain shedding of TLR4 and thereby decreases the
responsiveness of cells to LPS. ADAM10, activated by extracellular Ca2+ influx,
was implicated in the ectodomain cleavage of TLR4.
PMID- 28427049
TI - Predictive Validity of Two Physical Frailty Phenotype Specifications Developed
for Investigation of Frailty Pathways in Older People.
AB - BACKGROUND: For investigating the relationship of frailty with physical,
psychological, and social conditions on pathways, the frailty definition should
ideally exclude these conditions. Based on the frailty phenotype, 2 candidate
physical frailty specifications or instruments with 3 indicators, namely
slowness, weakness, and exhaustion, and 4 indicators with addition of weight loss
were previously developed, and had their construct and concurrent validity
demonstrated. OBJECTIVE: This study seeks to evaluate the predictive validity of
2 candidate physical frailty specifications with respect to death, functional
impairment, and poor quality of life in older people. METHODS: For 4,368
respondents aged 65-89 years from wave 2 of the English Longitudinal Study of
Ageing, confirmatory factor analysis is performed for these 2 physical frailty
specifications to obtain unique factor scores for each respondent. Prediction of
death, basic and instrumental activities of daily living (BADL and IADL)
difficulty, and poor quality of life (reverse of Control, Autonomy, Self
realization, and Pleasure [19 items] or CASP-19) 2 years later by factor scores
for these 2 specifications is evaluated using standardized coefficients, c
statistics, and r2 values from regression analyses. Their performance is compared
with those of alternative specifications with 3 (slowness, weakness, and weight
loss) and 5 indicators (slowness, weakness, exhaustion, weight loss, and low
physical activity), and Frailty Index (FI). RESULTS: For the 2 candidate
specifications, an increase of 1 standard deviation (SD) predicts 50-57% increase
in odds of death, 0.10-15 SD increase in change in BADL or IADL difficulty, and
poor quality of life at 2 years. They predict these outcomes as well or better
than the alternative specification with 3 indicators, but marginally worse than
that with 5 indicators. Compared with FI, they predict death and poor quality of
life similarly, but perform worse for functional impairment. Minor differences
are observed across gender. CONCLUSION: Reasonable predictive validity of 2
candidate physical frailty specifications based on the frailty phenotype with 3
and 4 indicators is demonstrated for death, functional impairment, and poor
quality of life. These findings offer evidence to support their suitability for
employment in investigating frailty pathways in older people.
PMID- 28427050
TI - Expression of High Mobility Group Protein B1 in Cardiac Tissue of Elderly
Patients with Coronary Artery Disease with or without Inflammatory Rheumatic
Disease.
AB - BACKGROUND: It is known from clinical practice and observational studies that
elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a
significantly increased risk for cardiovascular diseases such as coronary artery
disease (CAD) and heart failure. The molecular mechanism, however, is still not
known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly
conserved single polypeptide expressed in all mammal eukaryotic cells, has been
identified to mediate myocardial dysfunction in vitro once released from the
nuclei of cardiomyocytes. OBJECTIVE: To investigate whether HMGB1 and its
receptors are expressed in cardiac muscles of elderly patients with CAD with or
without IRD. METHODS: HMGB1 and its 3 well-known receptors, receptor for advanced
glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by
immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with
CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were
measured by Western blot from the cardiac biopsies in 5 patients with and 5
without IRD. RESULTS: Pathologic cytosolic HMGB1 in cardiomyocytes was massively
recorded in all patients with IRD, but only slightly expressed in 1 patient
without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle
biopsies of patients with IRD compared to those without IRD. Furthermore, all 3
HMGB1 receptors were expressed in cardiomyocytes of all patients. CONCLUSION: The
increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total
amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a
greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD
individuals. Thus, the HMGB1 signaling pathways may be more easily activated in
elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory
process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD
patients might reduce the risk for cardiovascular events.
PMID- 28427051
TI - Subjective Time Perceptions and Aging Well: A Review of Concepts and Empirical
Research - A Mini-Review.
AB - Human beings impose subjective, time-related interpretations on their existence,
and the experience of time is a major aspect of lifespan development. In this
mini-review, we understand subjective time as the way individuals subjectively
perceive and evaluate the passing of their personal "objective" lifetime. A broad
range of constructs and operationalizations has been developed in (gero-)
psychology to capture subjective time, including future time perspective,
personal goals, or autobiographical memories. In order to theoretically integrate
this yet loosely connected body of literature, we propose a conceptual model of
subjective time concepts according to 2 dimensions: temporal direction (past,
present, future) and thematic field (duration/expansion, time-ordered life
content, and time-related evaluations, attitudes, and mindsets). This conceptual
model of subjective time perceptions builds the foundation for a review of the
empirical literature regarding associations of subjective time with developmental
outcomes (i.e., subjective well-being and physical health) in middle and late
adulthood. Empirical findings establish subjective time concepts as a consistent
predictor of well-being and health. Positive subjective time perceptions (i.e.,
an expanded view of the future, a focus on positive past and future life content,
and favorable time-related evaluations) were associated with higher well-being
and better physical health, while negative subjective time perceptions in general
were linked to lower levels of health and well-being. Contrasting past- and
future-oriented subjective time perceptions, it appears that past-oriented
subjective time perceptions have been studied primarily in relation to subjective
well-being, while future-oriented time perceptions play a key role both with
regard to physical health and well-being. In conclusion, we argue that a stronger
integration of subjective time constructs into developmental regulation models
may deepen our understanding of human development across the lifespan. To this
end, we call for theoretical and empirical interlinkages between yet loosely
connected conceptual developments related to subjective time. These endeavors
should be paralleled by an extension of methodological procedures (e.g.,
implementation of longitudinal research designs as well as a focus on the oldest
old) in order to inform a "lifespan theory of subjective time."
PMID- 28427052
TI - Glucosylceramide Critically Contributes to the Host Defense of Cystic Fibrosis
Lungs.
AB - BACKGROUND: Cystic fibrosis (CF) is the most common autosomal-recessive disorder
in western countries. Previous studies have demonstrated an important role of
sphingolipids in the pathophysiology of cystic fibrosis. It has been shown that
ceramide has a central role in various pulmonary infections, including those with
Pseudomonas aeruginosa (P. aeruginosa). Ceramide is accumulated in the airways of
CF mice and patients. However, little is known about a potential role of
glucosylceramide in cystic fibrosis. METHODS: We investigated the expression of
glucosylceramide and lactosylceramide in the respiratory tract of murine and
human CF samples by immunohistochemistry and analyzed effects of glucosylceramide
on P. aeruginosa in vitro. We performed pulmonary infections with P. aeruginosa
and tested inhalation with glucosylceramide. RESULTS: We demonstrate that
glucosylceramide is down-regulated on the apical surface of bronchial and
tracheal epithelial cells in cystic fibrosis mice. Although glucosylceramide did
not have a direct bactericidal effect on Pseudomonas aeruginosa in vitro,
inhalation of CF mice with glucosylceramide protected these mice from infection
with P. aeruginosa, while non-inhaled CF mice developed severe pneumonia.
CONCLUSION: Our data suggest that glucosylceramide acts in vivo in concert with
ceramide and sphingosine to determine the pulmonary defense against P.
aeruginosa.
PMID- 28427053
TI - Growing Skull Fracture and the Orbitocranial Variant: Nuances of Surgical
Management.
AB - AIMS: Growing skull fracture (GSF) is a rare complication resulting from
diastatic enlargement of a pediatric skull fracture. Orbitocranial GSF is a
distinct variant with more complex management issues due to the displacement of
the globe. This study aims to discuss surgical considerations in the management
of GSF, with particular reference to orbitocranial variants. METHODS: We
conducted a retrospective analysis of 7 children operated for GSFs at our
institute from 2008 to 2015. RESULTS: Four boys and 3 girls were operated during
this period. The mean age at initial trauma was 2 years, and most of them
sustained falls. The most frequent symptoms of GSF were progressive scalp
swelling and proptosis. The most common location was the orbitofrontal region.
Duraplasty with cranioplasty was performed in 5 patients, while duraplasty alone
was only required in 2 patients. A postoperative complication was noted in 1
patient and managed successfully. Good cosmetic results were obtained in all of
the cases. CONCLUSIONS: Duraplasty is essential in the repair of GSF and should
be followed by cranioplasty to prevent recurrent leptomeningeal herniation. We
recommend the use of autologous bone from the surgical site for cranioplasty.
Orbital roof repair is advisable for good visual and cosmetic outcome in
orbitocranial variants of GSF.
PMID- 28427054
TI - Preceding Intravenous Thrombolysis in Patients Receiving Endovascular Therapy.
AB - BACKGROUND: The beneficial effects of endovascular therapy (EVT) in acute
ischemic stroke have been demonstrated in recent clinical trials using new
generation thrombectomy devices. However, the comparative effectiveness and
safety of preceding intravenous thrombolysis (IVT) in this population has rarely
been evaluated. METHODS: From a prospective multicenter stroke registry database
in Korea, we identified patients with acute ischemic stroke who were treated with
EVT within 8 h of onset and admitted to 14 participating centers during 2008
2013. The primary outcome was a modified Rankin Scale (mRS) score at 3 months.
Major secondary outcomes were successful recanalization defined as a modified
Treatment in Cerebral Ischemia score of 2b-3, functional independence (mRS score
0-2), mortality at 3 months, and symptomatic hemorrhagic transformation (SHT)
during hospitalization. Multivariable logistic regression analyses using
generalized linear mixed models were performed to estimate the adjusted odds
ratios (ORs) of preceding IVT. RESULTS: Of the 639 patients (male, 61%; age 69 +/
12; National Institutes of Health Stroke Scale score of 15 [11-19]) who met the
eligibility criteria, 458 received preceding IVT. These patients showed lower mRS
scores (adjusted common OR, 1.38 [95% CI 0.98-1.96]). Preceding IVT was
associated with successful recanalization (1.96 [1.23-3.11]) and reduced 3-month
mortality (0.58 [0.35-0.97]) but not with SHT (0.96 [0.48-1.93]). CONCLUSION: In
patients treated with EVT within 8 of acute ischemic stroke onset, preceding IVT
may enhance survival and successful recanalization without additional risk of
SHT, and mitigate disability at 3 months.
PMID- 28427055
TI - Aquaporin-4 Mediates the Suppressive Effect of Lipopolysaccharide on Hippocampal
Neurogenesis.
AB - OBJECTIVE: Aquaporin-4 (AQP4), a key molecule for water homeostasis in the brain,
is associated with adult neurogenesis, but its mechanisms regulating adult neural
stem cells (aNSC) remain largely unexplored. Neuroinflammation has a relevant
influence on adult neurogenesis, which is a common feature in various
neurodegenerative diseases. Considering the possible link between
neuroinflammation and AQP4, we speculate that AQP4 may mediate the synthesis and
release of proinflammatory cytokines in glia and then indirectly regulate adult
hippocampal neurogenesis. METHODS: Using AQP4 knockout mice, we investigated the
effects of AQP4 on hippocampal neurogenesis after lipopolysaccharide (LPS)
induced neuroinflammation. RESULTS: We unexpectedly found that AQP4 deficiency
attenuated the decrease in aNSC proliferation after systemic LPS exposure,
accompanied by inhibition of glial activation and suppression of the production
of proinflammatory cytokines in the hippocampus. Meanwhile, in vivo studies
demonstrated that LPS-induced activated microglia did not express AQP4,
indicating the impossibility of direct regulation of AQP4 to activate microglia.
Furthermore, we demonstrated in vitro that AQP4 deficiency inhibited astrocyte
activation and reduced the release of proinflammatory cytokines from astrocytes.
CONCLUSION: Our data suggest that AQP4 mediates the suppressive effect of
neuroinflammation on hippocampal neurogenesis via regulation of the astroglial
response.
PMID- 28427056
TI - Blood Pressure during the Immediate Neonatal Transition: Is the Mean Arterial
Blood Pressure Relevant for the Cerebral Regional Oxygenation?
AB - BACKGROUND: Measurement of mean arterial blood pressure (MABP) is feasible during
neonatal transition. OBJECTIVE: The objective of this study was to investigate a
potential influence of MABP on the cerebral regional oxygen saturation (crSO2) in
preterm and term infants during the immediate neonatal transition. MATERIALS AND
METHODS: Preterm and term infants were included in this observational study. The
crSO2 was measured by near-infrared spectroscopy with the INVOS 5100C (Somanetics
Corp., Troy, MI, USA) during the immediate neonatal transition (15 min after
birth). The near-infrared spectroscopy sensor was applied to the left forehead.
Furthermore, a pulse oximeter was applied to monitor arterial oxygen saturation
(SpO2) and heart rate (HR). Fifteen minutes after birth, blood pressure was
measured noninvasively at the left upper arm. Cerebral fraction tissue oxygen
extraction (cFTOE) was calculated from SpO2 and crSO2. To investigate a potential
association between crSO2/cFTOE and MABP, we performed a correlation analysis.
RESULTS: A total of 462 preterm and term infants (186/292) were included. Mean
gestational age was 31.0 +/- 3.5 weeks for preterm infants and 38.9 +/- 0.8 weeks
for full term infants. Mean birth weight was 1.591 +/- 630 g in preterm infants
and 3.331 +/- 461 g in term infants. There was a significant negative correlation
between MABP and cFTOE (rho = -0.19, p = 0.03) in preterm infants but not in term
infants (rho = 0.05, p = 0.39). There was no significant correlation between MABP
and crSO2 in either group. CONCLUSION: MABP has an impact on cerebral oxygenation
in preterm infants. Therefore, blood pressure monitoring during the immediate
neonatal transition might be relevant for improving cerebral oxygenation
especially in preterm infants.
PMID- 28427057
TI - Long-Term Anatomical and Functional Outcomes in Patients with Ischemic Central
Retinal Vein Occlusion Treated with Anti-Vascular Endothelial Growth Factor
Agents.
AB - PURPOSE: To evaluate the anatomical and functional outcomes in patients with
ischemic central retinal vein occlusion (CRVO) treated with intravitreal anti
vascular endothelial growth factor (VEGF) agents. METHODS: This retrospective
study included 15 treatment-naive patients with ischemic CRVO and macular edema
who were treated with intravitreal ranibizumab or aflibercept. The main outcomes
were the evolution of retinal ischemia over time, as well as the change in best
corrected visual acuity (BCVA) and in central subfield thickness (CST) at month
24. RESULTS: At month 24, patients with ischemic CRVO gained +7.8 letters
compared to baseline, while there was a significant decrease in CST by 243.7 MUm.
At baseline, ischemia was located mainly at the peripheral retina, while 6.6% of
patients presented macular ischemia. At month 24, 20% of patients had macular
ischemia, which was found to be negatively correlated with BCVA. The patients
with macular ischemia had very poor final visual outcome and were advised to
discontinue treatment. CONCLUSIONS: Our study showed that anti-VEGF treatment was
effective in patients with ischemic CRVO, since it reduces macular edema and
maintains or improves VA in the long term (24-month follow-up). It is worthy of
note that in a small proportion of patients (13.3%) peripheral ischemia
progressed to macular ischemia over time. In cases where macular ischemia is
present, anti-VEGF treatment does not seem to offer any improvement in VA.
PMID- 28427058
TI - Dietary Selenium or Zinc Supplementation Restores Brain Lipid Composition and
Membrane Fluidity in Protein-Undernourished Rats.
AB - Studies have shown that protein undernutrition (PU) modifies the membrane lipid
composition in the intestine and liver, as well as in plasma and other areas.
However, there is limited information on the effect of PU on synaptosomal
membrane lipid composition and fluidity and the protective role of selenium (Se)
and zinc (Zn), which is a major focus of the present study. For 10 weeks, rats
were fed diets containing 16% casein, which constituted the adequate protein
diet, or 5% casein, representing the PU diet. The animals were supplemented with
Se and Zn at a concentration of 0.15 and 227 mg L-1, respectively, in drinking
water for 3 weeks. The results showed a significant increase in total lipids,
glycolipids, triglycerides, cholesterol, and the cholesterol/phospholipid
(Chol/PL) ratio, and a significant reduction in phospholipids and membrane
fluidity. Se and Zn supplementation to PU rats, however, significantly lowered
total lipids, glycolipids, triglycerides, cholesterol, and the Chol/PL ratio,
while phospholipids and membrane fluidity were significantly restored. It is
concluded that a perturbed lipid composition induced by PU affects the membrane
structure and fluidity, which in turn influences membrane functions. The study
suggests that Se and Zn supplementation might be beneficial in restoring the
lipid dyshomeostasis associated with PU.
PMID- 28427059
TI - The Burden of Diabetes: Emerging Data.
AB - In recent times, the global prevalence of diabetes has increased substantially,
reaching 8.3% in 2014, which corresponds to 387 million patients. Studies in
Europe and USA have shown increased incidence of type 1 Diabetes (T1D) over time
at a rate of 3-5% per year. Another most worrying feature of the rapid increase
of diabetes is the emergence of type 2 Diabetes (T2D) in children, adolescents,
and young adults. The well-known behavioral risks factors and epigenetic
mechanisms recently observed require an integrated approach to prevent T2D.
Diabetes significantly influences the patient' survival, quality of life, and
development of organ system degeneration. Epidemiological studies have shown
increased mortality in diabetic patients, especially women, which increased
approximately fivefold, whereas cardiovascular mortality increased 20- to 30-fold
when compared to the normal population. Diabetes is the leading cause of end
stage renal disease and vision loss in developed countries. Around 40% of T1D and
T2D start on renal replacement therapy. While after 40 years of diabetes, the
cumulative proportion of patients with any retinopathy and advanced retinopathy
was 84.1 and 50.2%, respectively. However, the most prevalent chronic
complication of diabetes is neuropathy. Distal Symmetric Polyneuropathy occurs in
at least 20% of people with T1D after 20 years and in 10-15% of newly diagnosed
T2D, increasing to 50% after 10 years. Cardiovascular Autonomic Neuropathy may be
present in up to 60% of patients after 15 years and is an independent risk factor
for cardiovascular mortality.
PMID- 28427060
TI - The Eye as a Window to the Microvascular Complications of Diabetes.
AB - Although microvascular complications of diabetes (retinopathy, neuropathy, and
nephropathy) affect different organs, they are strongly correlated to each other.
Based on recent data, their onset and progression could be directly monitored,
focusing our attention only on the eye. When confirmed and standardized, this
approach could allow one to simplify the way in which we follow the progression
of different diabetic complications, and thus establish new strategies aimed at
preventing, treating and, hopefully, inducing the remission of microvascular
complications of diabetes.
PMID- 28427061
TI - Emerging Insights into Pathogenesis.
AB - Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM).
Persistent hyperglycemia leads to the activation of multiple cellular pathways
involved in the pathogenesis of DR, resulting in increased inflammation,
oxidative stress, and vascular dysfunction. DR has been considered a "chronic,
low-grade inflammatory disease of the retina". However, an increasing body of
evidence suggests that inflammation and neurodegeneration both occur in human
diabetes even before the development of clinical signs of DR. One of the first
signs of inflammation in DM is the activation of retinal glia cells (RGC). RGC
include microglia and macroglial cells (Muller cells and astrocytes). Activated
RGC release cytotoxic substances responsible for the recruitment of leukocytes,
blood-retinal barrier breakdown, direct glial dysfunction, and neuronal cell
death. Recently, many inflammatory mediators, growth factors, and other molecules
have been investigated in human vitreous and aqueous humor samples to better
understand, in vivo, the multiple pathways and mechanisms leading to the
pathogenesis of DR and its complications, such as diabetic macular edema, with
potential for more tailored treatment. Moreover, non-invasive techniques, like
optical coherence tomography, have allowed to detect new findings in the retinal
layers, such as the hyperreflective intraretinal spots, which have been
hypothesized to represent an in vivo marker of microglial activation, and early
neural cell loss, confirming the hypothesis that neurodegeneration occurs early
both in type 1 and 2 diabetes. These new emerging insights foster a better
understanding of the pathogenesis of DR, which can no longer be considered as a
pure retinal vascular complication of DM.
PMID- 28427062
TI - Emerging Issues for Optical Coherence Tomography.
AB - Almost 25 years after its introduction, optical coherence tomography (OCT) is
still a crucial test in the evaluation of patients affected by diabetic
retinopathy. In this chapter, the authors provide an extensive overview of the
posterior segment pathological changes induced by diabetes, characterized using
OCT. OCT plays a key role in diabetic macular edema (DME) as it assesses related
retinal changes both in a qualitative (i.e., DME pattern, presence and aspects of
cysts, fluid localization, integrity, and reflectivity of retinal layers) and
quantitative (i.e., macula volume, central and sectorial retinal thickness) way,
and it is therefore essential for diagnosis, characterization, and follow-up of
DME. Diabetic macular ischemia is associated with retinal structural changes
which can be investigated using OCT, although its diagnosis relies mostly on
fluorescein angiography. Beyond DME and macular ischemia, OCT permits the
individuation of many other lesions occurring in the setting of both non
proliferative (i.e., hyperreflective spots, micropseudocysts, hard exudates,
microaneurysm, cotton-wool spots) and proliferative (i.e., neovascularization,
vitreoschisis, tractional retinal detachment, hemorrhage) retinopathies. OCT
provides precious information on several structures, including vitreo-retinal
interface, retinal nerve fiber layers, ganglion cell complex, and choroid.
PMID- 28427063
TI - Optical Coherence Tomography Angiography in Diabetic Maculopathy.
AB - Fluorescein angiography (FA) and indocyanine green angiography have provided
information about the normal retinal and choroidal anatomy, nearly comparable to
histological findings. These tests have been fundamental in the evaluation of all
retinal and choroidal vascular diseases and have allowed clinicians to define and
diagnose several pathological conditions. FA became the "gold standard" in
retinal imaging due to the capacity to visualize the retinal capillary bed and
its changes, both in the macular area and in the periphery. Although the
fluorescence of the injected dye enabled improved visualization of retinal
capillaries, not all the different layers of the retinal capillary network could
be visualized in this bi-dimensional examination, mainly because of the light
scattering phenomenon. By calculating the difference between static and non
static tissues, optical coherence tomography angiography (OCT-A) allows a depth
resolved visualization of the retinal and choroidal microvasculature. Given that
the main moving elements in the ocular fundus are contained in blood vessels,
determining a vascular decorrelation signal enables visualization of the 3
dimensional retinal and choroidal vascular networks without the intravenous dye
injection, reducing therefore the risk of potential adverse events. Since OCT-A
is perfectly co-registered with its structural OCT, both morphological findings,
such as macular edema, and functional ones, like capillary drop-out, may be
clearly evaluated on a single dye-free examination. Proficient detection of the
different findings in diabetic maculopathy on OCT-A can result in a rapid
analysis of the examination, and in the capacity to distinguish truly
decorrelated structures (perfused vessels) from artifacts. Moreover, a complete
morpho-functional assessment may help in determining both the origin and the
clinical activity of a given vascular disease.
PMID- 28427064
TI - Emerging Issues for Ultra-Wide Field Angiography.
AB - Fluorescein angiography (FA) is a useful test in patients affected by diabetic
retinopathy (DR) to evaluate the blood-retinal barrier integrity and the presence
of non-perfused areas, vascular leakage, microvascular abnormalities, and
neovascularization. The peripheral retina is involved in most DR lesions, and,
thus, its proper visualization is crucial for the screening, diagnosis,
monitoring, treatment, and prognosis of DR. To expand the field of view, wide
field and ultra-wide-field imaging have been developed, allowing images up to 200
degrees of retinal surface in one single photo. In this chapter, emerging issues
concerning ultra-wide-field FA in DR are illustrated.
PMID- 28427065
TI - Emerging Simplified Retinal Imaging.
AB - Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a
significant impact on the world's health systems. Globally, the number of people
with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and it is
estimated that the number with vision-threatening diabetic retinopathy will
increase from 37.3 million to 56.3 million if prompt action is not taken. Lack of
early diagnosis and management is the leading cause of blindness in working-age
populations The gap between demand and annual eye examinations has been a big
challenge. Furthermore lack of availability of cost effective simplified retinal
imaging tools has limited the diabetic retinopathy screening program in many
parts of the world in last few decades. This has led to the development of
innovative ideas and availability of cost effective simplified retinal imaging
tools. In this chapter we will be describing some of the well known commercially
available emerging simplified (Non Tabletop, Hand Held, Portable) retinal imaging
tools that have potential to help in screening diabetic retinopathy with ease and
without increasing financial burden.
PMID- 28427066
TI - Intravitreal Ranibizumab in Diabetic Macular Edema: Long-Term Outcomes.
AB - Intravitreal ranibizumab (RBZ) has been shown in multiple randomized clinical
trials to be a valuable treatment for diabetic macular edema (DME), promoting a
significant improvement in best-corrected visual acuity (BCVA) and in anatomic
outcomes. Compared to sham (RISE and RIDE studies), RBZ rapidly and sustainably
improved BCVA and decreased macular edema at 2 years, reducing the risk of
further vision loss, with low rates of local or systemic side effects. Compared
to macular laser photocoagulation (READ-2 study), RBZ provided a greater
improvement in BCVA and regression in foveal thickness, but required a higher
number of injections compared to patients treated with both RBZ and laser. In
RESTORE trial, RBZ alone or combined with macular laser turned out to be superior
to laser alone, without significant differences between the 2 RBZ groups.
Compared to combined treatment (RBZ or triamcinolone associated with macular
laser) or photocoagulation laser alone (Diabetic Retinopathy Clinical Research
Network trial), RBZ with prompt or deferred laser was more effective than laser
alone at 1-year follow-up. At 3 years, prompt laser was not better than deferring
laser for 24 weeks or more. At 5 years, subjects treated with RBZ achieved better
long-term visual outcomes than patients managed with triamcinolone or laser
followed by very deferred RBZ. In conclusion, randomized clinical trials showed
that RBZ was superior to laser in DME treatment, providing excellent long-term
visual outcomes. Frequent injections were necessary in most of the patients to
properly control DME and maximize the visual benefits.
PMID- 28427067
TI - Intravitreal Aflibercept in Diabetic Macular Edema: Long-Term Outcomes.
AB - For decades, macular laser photocoagulation has been the standard of care in the
treatment of diabetic macular edema (DME). With the relatively recent advent of
anti-vascular endothelial growth factor (VEGF) agents, DME treatment has entered
a new era. VEGF is a well-known pro-angiogenic and pro-permeability factor
involved in the pathogenesis of DME. VEGF blockade has proven remarkably
effective at reducing DME and improving visual acuity (VA) in eyes with center
involved DME causing VA loss in several randomized controlled trials (RCTs).
Intravitreal aflibercept, ranibizumab, and bevacizumab (the latter used off
label) are 3 anti-VEGF molecules currently available for DME treatment.
Aflibercerpt is a 115-kDA recombinant fusion protein consisting of VEGF binding
domains of human VEGF receptors-1 and -2 fused to the Fc domain of human
immunoglobulin-G1. The ability to bind placental growth factors 1 and 2 (which is
another pro-permeability mediator) and a theoretically long half-life are
potential advantages of aflibercept over other anti-VEGF agents. The use of
intravitreal aflibercept in DME treatment has been investigated in several RCTs.
The aim of this chapter is to briefly report on the current evidence for treating
DME with intravitreal aflibercept.
PMID- 28427068
TI - Intravitreal Steroids in Diabetic Macular Edema.
AB - Over the past decade, great strides have been made in the management of diabetic
macular edema (DME). Therapeutic alternatives now include focal/grid laser
photocoagulation, vitreo-retinal surgery, and intraocular injection of anti
angiogenic and steroid molecules. Intravitreal administration of steroids
represents a fundamental alternative for recalcitrant and naive eyes with DME,
especially in those cases when anti-vascular endothelial growth factor (VEGF)
agents are contraindicated or a treatment regimen with fewer intravitreal
injections is required. Currently, 3 intravitreal corticosteroid options for DME
treatment are available: the dexamethasone delivery system, the fluocinolone
acetonide insert, and off-label intravitreal triamcinolone acetonide. All 3
agents are associated with risk of cataract progression and intraocular pressure
elevation, but they maintain a good safety profile. In patients who remain
unresponsive to anti-VEGF therapy, are pseudophakic, at low risk for glaucoma, or
who have significant cardiovascular risk, treatment with long-lasting intraocular
steroids is suggested. There still remain many unanswered questions about
intravitreal drugs, regarding dose, frequency, the correct regimen of each
treatment, and the potential long-term side effects.
PMID- 28427069
TI - Practical Lessons from Protocol I for the Management of Diabetic Macular Edema.
AB - Protocol I, a multicenter randomized clinical trial, compared the visual outcomes
of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or
deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser,
or sham injection with prompt laser for the treatment of center-involving
diabetic macular edema (DME). A total of 854 adult patients with type I or II
diabetes and any level of non-proliferative diabetic retinopathy or proliferative
retinopathy with adequate panretinal photocoagulation, with best-corrected visual
acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320)
and visual loss attributed to macular edema, or retinal thickening with central
subfield thickness of at least 250 um by OCT were enrolled. The main outcomes
relevant for practicing clinicians are as follows. (1) Intravitreal ranibizumab
treatment provides superior visual outcomes compared to conventional laser
treatment. (2) Adjunctive laser treatment does not appear to provide substantial
visual benefit compared to ranibizumab treatment alone, but may reduce the number
of injections required to resolve DME. Deferral of laser is likely beneficial in
patients with worse initial visual acuity. (3) Intravitreal triamcinolone
provides similar visual outcomes compared to intravitreal ranibizumab in
pseudophakic patients but is associated with a clinically important increased
risk of increased intraocular pressure (IOP), need for glaucoma medications, and
need for glaucoma surgery. (4) Delayed initiation of intravitreal ranibizumab
therapy provides improved visual outcome among patients initially treated with
conventional laser photocoagulation or triamcinolone, but the magnitude of the
benefit is not as great as is observed when ranibizumab treatment is initiated
promptly. (5) The number of ranibizumab injections required to achieve the
desired visual outcome decreases substantially after the first year, with the
majority of patients not requiring further treatment after 3 years. (6) Patients
who do not have a rapid response to ranibizumab still display long-term benefit
to continued therapy, although perhaps less than those with immediate
improvement. (7) Intravitreal ranibizumab is not only effective in reducing
retinal edema and improving BCVA among patients with DME, it is also a disease
modifying therapy and induces improvement of the diabetic retinopathy severity
score by 2 or more steps in approximately one third of patients. Triamcinolone
injection also induces improvement in diabetic retinopathy severity in DME
patients, but perhaps to a lesser degree. (8) No increased risk of systemic
adverse events was observed among patients treated with intravitreal ranibizumab
compared to sham-injected controls or triamcinolone-treated patients, but the low
frequency of adverse events, restrictive enrollment criteria, and specific
posology employed in this study limit the generalization of this conclusion to
patients routinely encountered in clinical practice. (9) There was no clinically
important increased risk of major ocular complications among patients treated
with intravitreal ranibizumab (including the risk of glaucoma), although
endophthalmitis is a potentially devastating outcome should it occur. In addition
to the risk of endophthalmitis, intravitreal triamcinolone injection was
associated with clinically important increased risk of cataract progression and
increased IOP.
PMID- 28427070
TI - Practical Lessons from Protocol T for the Management of Diabetic Macular Edema.
AB - PURPOSE: To review the results of Diabetic Retinopathy Clinical Research Network
Protocol T, as applied to clinical practice. METHODS: Review of major
publications reporting the results of Protocol T, a randomized single-masked (in
year-1 only), multicenter clinical trial comparing aflibercept, bevacizumab, and
ranibizumab as treatment option for center-involving diabetic macular edema
(DME). The main outcome measures were change in visual acuity (VA), central
subfield thickness (CST) on optical coherence tomography, cost effectiveness,
burden of care, and safety. RESULTS: A total of 660 participants (mean age 61 +/-
10 years, 47% women, 65% Caucasian) were randomized to treatment with aflibercept
(n = 224), ranibizumab (n = 218), or bevacizumab (n = 218). The majority of
patients (90%) had type II diabetes, with an average duration of 17 +/- 11 years.
About half the patients had baseline ETDRS VA of 20/32 to 20/40, and half had
ETDRS VA of 20/50 to 20/320 in all 3 cohorts. Patients in all 3 cohorts received
a similar number of injections during the study period (9-10 in year-1; 5-6 in
year-2). The year-1 improvement in ETDRS letters was significantly higher for
aflibercept than for ranibizumab and bevacizumab in patients with baseline VA
20/50 or worse (p = 0.003 and p < 0.001, respectively), but was no different in
patients with better baseline VA of 20/32 to 20/40 (p = 0.69). By year-2, among
patients with poorer baseline VA, there was a difference in mean letters gained
between aflibercept and bevacizumab (p = 0.02), but no difference between
aflibercept and ranibizumab (p = 0.18). At year-2, there was no clinically
meaningful difference in VA improvement (i.e., gain or loss of >=10 or >=15
letters) among any of the agents (p > 0.74). Bevacizumab was less effective than
the other agents in decreasing CST at years-1 and -2 in the overall cohort of
patients (p < 0.001). However, bevacizumab is substantially cheaper and much more
cost-effective (when comparing expense and quality of life measures) than
aflibercept and ranibizumab. The cost of other agents would have to decrease by
80-90% to be cost-effective relative to bevacizumab. Intravitreal administration
of anti-VEGF therapy has relatively few ocular and systemic side effects, but
caution may be warranted for patients with a recent history or high risk of
myocardial infarction or stroke. CONCLUSIONS: Aflibercept, bevacizumab, and
ranibizumab are highly effective treatments for DME. Bevacizumab is more cost
effective than aflibercept and ranibizumab. Intravitreal administration of drugs
is relatively safe; however, intravitreal administration may be associated with
severe systemic side effects in a small percentage of patients, particularly in
those with a prior history of or high risk of Anti-Platelet Trialists'
Collaboration events.
PMID- 28427071
TI - Is Laser Still Important in Diabetic Macular Edema as Primary or Deferral
Therapy?
AB - Laser treatment was used in the past to reduce the visual loss due to diabetic
macular edema. The recent advent of anti-vascular endothelial growth factor (anti
VEGF) has completely revolutionized the management of diabetic retinopathy, with
a significant improvement in the overall prognosis. Nevertheless, macular laser
can still be applied in selected cases characterized by retinal thickness <=400
microns, high visual acuity, extrafoveal location, and contraindications to the
intravitreal approach with anti-VEGF and steroids. In addition, the combined
therapy with anti-VEGF and macular laser can exploit the synergistic effects of
both therapies, leading to a simpler and more practical management of patients
over the long-term follow-up.
PMID- 28427072
TI - Anti-Vascular Endothelial Growth Factor Injections: The New Standard of Care in
Proliferative Diabetic Retinopathy?
AB - For decades, panretinal photocoagulation (PRP) has been the standard of care for
the treatment of proliferative diabetic retinopathy (PDR). The relatively recent
advent of anti-vascular endothelial growth factor (VEGF) formulations for
intravitreal injection has provided a fresh perspective on PDR treatment,
especially in eyes with concurrent diabetic macular edema (DME). The anti-VEGF
agent ranibizumab has demonstrated a potentially protective effect on eyes with
DME in terms of progression to PDR in the RIDE/RISE trials, as has aflibercept in
the VIVID/VISTA trials. In 2015, these 2 agents were approved by the Food and
Drug Administration for the treatment of PDR with DME, though PRP still remains
the standard of care for eyes without baseline DME. Published results from
Protocol S illustrate the non-inferiority of ranibizumab versus PRP in the
treatment of PDR, the first prospective study to do so in eyes with and without
baseline DME. These results also reveal that treatment with ranibizumab, when
compared to standard treatment with PRP, may also lead to less peripheral visual
field loss, reduced need for vitrectomy, and reduced chance for developing DME.
Both PRP and intravitreal ranibizumab have very low rates of adverse events.
However, treatment with anti-VEGF agents generally is associated with higher
costs, increased need for follow-up, and the risk of potentially catastrophic
ocular complications (e.g., endophthalmitis) and systemic side effects. Anti-VEGF
agents should be considered in cases of media opacity preventing completion of
PRP in compliant patients without recent cerebrovascular accident or myocardial
infarction, though the long-term efficacy of these agents remains to be studied,
especially after the discontinuation of injections.
PMID- 28427073
TI - Surgical Management and Techniques.
AB - Technical advancements have substantially extended the indications for surgery in
diabetic retinopathy (DR) during the last 40 years, from the traditional
indications including non-clearing vitreous hemorrhage, traction retinal
detachment (RD), and traction-rhegmatogenous RD, to epiretinal membrane (ERM),
vitreomacular traction, diffuse macular edema, neovascular glaucoma, and anterior
hyaloid fibrovascular proliferation. The goals of vitreoretinal surgery in DR are
multiple: clearing media opacities, release of traction (anteroposterior and/or
tangential), segmentation and/or removal of traction bands, peeling of ERMs,
hemostasis, laser photocoagulation, and tamponade of retinal breaks with gas or
silicone oil. The best management is achieved with integrated care provided by
physicians with expertise in medical management of diabetes and surgical care of
DR. In this chapter, the indications for surgery, preoperative considerations,
surgical techniques, and complications, together with their management, will be
discussed.
PMID- 28427074
TI - Enzymatic Vitreolysis for Vitreomacular Traction in Diabetic Retinopathy.
AB - Vitreomacular traction (VMT) is one of many possible factors involved in the
etiology of diabetic macular edema (DME). Pharmacologic vitreoretinal separation
is a potential alternative to vitrectomy for VMT in diabetic retinopathy. Small
case series have been published on the use of enzymatic vitreolysis in tractional
DME, and demonstrate that the enzymatic release of the posterior vitreous cortex
is more likely following the injection of plasmin enzyme. Further prospective and
randomized clinical trials are necessary to evaluate the clinical relevance of
ocriplasmin for vitreomacular traction in diabetic retinopathy, and additional
studies are needed to determine more accurately which patients might benefit most
from this treatment and how often and at what concentration ocriplasmin should be
administered.
PMID- 28427075
TI - Diabetic Macular Edema: Emerging Strategies and Treatment Algorithms.
AB - Diabetic macular edema (DME) is the most common cause of vision loss in diabetic
patients, and its management is often a long process requiring frequent
monitoring and therapeutic interventions. During the past several decades,
numerous treatments have been developed for the treatment of DME. Although many
of them have been found to be effective and safe, there is relatively little
comparative data, and no established guidelines for the optimal treatment
approach exist. In this chapter, the evolution of DME therapies is reviewed, and
the current common practice patterns are discussed. Available data from clinical
trials on the commonly used agents, as well as comparative studies and
combination therapies are reviewed. Additionally, recent advances and novel
treatment options that are currently being investigated are also discussed.
PMID- 28427076
TI - Application of Clinical Trial Results to Clinical Practice.
AB - Two critical questions one must answer as one applies the results of a clinical
trial to clinical practice are: (1) Regardless of whether the trial result is
likely to be replicated or reproduced in a second large-scale trial, are the
results likely to be reproduced in one's practice? (2) Regardless of whether the
experimental treatment was better than the alternative on average for a
population of patients, are the results clinically important for a given patient
in one's practice? To determine if a study result is likely to be reproduced in
one's clinical practice, it may be helpful to answer 5 questions: (1) Have steps
been taken to minimize bias? (2) Is the result likely due to the treatment? (3)
Is the result unlikely due to chance? (4) Is the study population representative
of one's patients? (5) Is the totality of evidence consistent? If the answer to
all 5 questions is "yes," then we posit that the trial result is likely to be
reproduced in one's practice. If not, the likelihood of reproducibility is low.
If the answer is yes to all questions except the last, then reproducibility in
one's practice is not clear and depends on the strength of the prior versus the
current evidence. If the prior evidence is strong, such as multiple pivotal
randomized clinical trials, and if the current trial result is not consistent
with the previous studies, then the current result may not be reproduced in one's
practice. To determine if a study result is clinically important, a 3-step
approach is suggested. Step 1. Decide, a priori, what a clinically meaningful
difference between 2 treatments would be. This choice defines regions of
beneficial, harmful, and trivial outcomes. Step 2. Identify the confidence
intervals (CIs). Determine whether the 95% CI mostly includes the range of
clinically beneficial outcomes and lies outside the range of clinically harmful
outcomes. If these conditions are met, the result is probably clinically
important, but the result may or may not be statistically significant. Put the
CIs and the regions of benefit/harm together to make a decision about clinically
important effects. Step 3. Assess the proportion of eyes with clinically
meaningful changes in vision. The proportion of "responders" among patients
receiving a given treatment reflects the likelihood of one's patient having a
clinically meaningful response to the treatment. In summary, not all
statistically significant results are reproduced, even those of carefully
designed clinical trials. Determining if a study result is likely to be
reproduced in one's practice is even more problematic. The 5-question test may
help in this regard. The 5-question test attempts to assess whether steps have
been taken to: minimize bias; avoid confounding; ensure adequate statistical
power to support precision in the estimates of population parameters; insure
external validity of the trial result; and determine whether there is a
convergence of evidence consistent with the trial's major findings. To determine
if a statistically significant result is likely to be clinically important, a 3
step approach may be useful, focusing on CIs and the proportion of eyes with
clinically meaningful changes in vision. Application of clinical trial results to
clinical practice requires critical analysis of the extant literature and good
clinical judgment.
PMID- 28427078
TI - A Case of Adult Metastatic Rhabdomyosarcoma of the Prostate Cured by Long-Term
Chemotherapy with Local Radiation.
AB - A 32-year-old man visited our hospital due to urinary retention. Prostate
specific antigen was 13.7 ng/mL. Imaging examinations showed a large prostatic
tumor and lung and internal iliac lymph node metastases. Transrectal biopsy
confirmed embryonal rhabdomyosarcoma of the prostate classified as cT2bN1M1
(stage IV) by the International Rhabdomyosarcoma Study (IRS) Group staging
system. Systemic chemotherapy was started according to the IRS III regimen 36,
which consisted of 16 weeks of induction chemotherapy with radiation. After 20
weeks, magnetic resonance imaging showed the disappearance of metastases, and the
prostate tumor shrunk markedly. Moreover, prostatic re-biopsy showed no viable
tumor cells. Maintenance chemotherapy, excluding vincristine because of severe
peripheral nerve disorder, was performed for 2 years. There has been no
recurrence for 49 months after the termination of maintenance chemotherapy. To
the best of our knowledge, this is the longest surviving case of adult-onset
metastatic rhabdomyosarcoma of the prostate reported in the literature.
PMID- 28427077
TI - MYBL2 is a Potential Prognostic Marker that Promotes Cell Proliferation in
Gallbladder Cancer.
AB - BACKGROUND: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary
tract malignancy, with extremely poor prognosis. In the present study, we
analyzed the potential involvement of MYBL2, a member of the Myb transcription
factor family, in the carcinogenesis of human GBC. METHODS: MYBL2 expression
levels were measured in GBC and cholecystitis tissue specimens using quantitative
real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of
MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting
Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU)
retention assay, flow cytometry analysis, western blot, and a xenograft model of
GBC cells in nude mice. RESULTS: MYBL2 expression was increased in GBC tissues
and associated with histological differentiation, tumour invasion, clinical stage
and unfavourable overall survival in GBC patients. The downregulation of MYBL2
expression resulted in the inhibition of GBC cell proliferation, and DNA
replication in vitro, and the growth of xenografted tumours in nude mice.
Conversely, MYBL2 overexpression resulted in the opposite effects. CONCLUSIONS:
MYBL2 overexpression promotes GBC cell proliferation through the regulation of
the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a
potential prognostic and therapeutic biomarker in GBC patients.
PMID- 28427079
TI - Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural
Effusion: An Updated Meta-Analysis.
AB - BACKGROUND: The role of combinations of tumor markers such as carcinoembryonic
antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a
fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has
not been clearly established. OBJECTIVES: This meta-analysis was performed to
establish the overall diagnostic accuracies of combinations of these pleural
fluid tumor markers for MPE. METHODS: The PubMed, Ovid, Embase, Web of Science,
and Cochrane bibliographic databases were searched. Sensitivity, specificity, and
other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3,
CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic
review of English-language studies. RESULTS: Twenty studies met the inclusion
criteria. For pleural fluid tumor marker combinations including more than 3
studies, the summary estimates of the sensitivity/specificity for diagnosing MPE
were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19
9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94.
CONCLUSIONS: In patients with undiagnosed pleural effusion, the combinations of
positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for
pleural malignancy, but the sensitivity of these tests is poor. Therefore, their
routine role in the diagnostic algorithm of these patients is questionable, and
management decisions should depend on positive cytological or biopsy results from
the pleura.
PMID- 28427080
TI - Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a
Stimulated Condition of Immunoglobulin A Nephropathy.
AB - : Backgroud/Aims: The aim of this study was to investigate the potential
renoprotective effect of rapamycin on the autophagy of podocytes treated with the
supernatant of mesangial cells cultured with aggregated IgA1 (aIgA1) from
immunoglobulin A nephropathy (IgAN) patients. METHODS: Monomeric IgA1 (mIgA1) was
isolated from the serum of IgAN patients or healthy volunteers, and then
transformed to aIgA1 by heating. Subsequently, the aIgA1-mesangial cell
supernatant was prepared by collecting the medium of mouse mesangial cells
(MSC1097) cultured with aIgA1 (100 mg/L) from different IgAN patients or healthy
volunteers for 48 h. Subsequently mouse podocytes (MPC5) were exposed to the
supernatant of the aIgA1-mesangial cells for 24 h, using 100 mg/L aIgA1 from
healthy volunteers as the control group or 100 mg/L aIgA1 from IgAN patients as
the IgANs group, in RPMI 1640 medium. The MPC5 cells in the IgANs+Rap group were
cultured with rapamycin (10 nmol/L) and the supernatant of MSC-1097 cells
cultured with aIgA1 from IgAN patients in RPMI 1640 medium. Autophagy was
assessed by western blot analysis (LC3, p62), electron microscopy, and
immunofluorescence staining (LC3, p62, and CD63). The apoptosis of podocytes was
evaluated by flow cytometry, and the expression of apoptosis-associated proteins
cleaved-caspase-3 and caspase-3 were determined by western blot analysis.
RESULTS: Deficient autophagy, which was evident by decreased LC3-II and CD63
levels, caused accumulation of p62, and fewer autophagosomes were observed in the
MPC5 cells cultured with the IgAN supernatant, along with stronger expression of
cleaved caspase-3 and a higher apoptosis rate. Inhibition of autophagy was
alleviated in the IgANs+Rap group. The LC3-II/LC3-I ratio increased by almost
30%, the accumulated p62 amount was reduced by 50%, and the number of
autophagosomes per podocyte increased to about 7 times that of the IgAN groups.
These results were confirmed by immunofluorescence staining. In addition, the
apoptosis rate of MPC5 cells decreased from 19.88% in the IgAN group to 16.78% in
the IgANs+Rap group, which was accompanied by a weaker expression level of
cleaved caspase-3. CONCLUSIONS: Rapamycin can reduce the apoptosis of podocytes
by inducing autophagy in IgAN.
PMID- 28427081
TI - Choroidal Thickness and Microperimetry Sensitivity in Age-Related Macular
Degeneration.
AB - PURPOSE: To assess choroidal thickness (CT) and its relationship to retinal
sensitivity in mild/moderate age-related macular degeneration (AMD). METHODS:
Seventy-two eyes of 51 participants with mild/moderate AMD and 36 eyes of 18 age
matched normal participants were prospectively recruited to undergo enhanced
depth imaging optical coherence tomography (EDI-OCT) imaging and microperimetry
(MP) functional assessment. OCT-measured CT and retinal thickness (RT) were
matched with MP sensitivity at 13 retinal loci, and correlations were analysed.
RESULTS: Patients with AMD had an average RT 56.5 MUm greater than those without
AMD (p < 0.001). There was no significant difference in CT between normal and AMD
participants (p = 0.36). In patients without atrophy or pigment epithelial
detachment, there was no correlation between MP sensitivity and CT (p = 0.08);
however, a correlation between RT and MP was detected (b = 0.006, p = 0.046).
Among patients without AMD, MP sensitivity was positively correlated with RT (b =
0.007, p < 0.001) and negatively correlated with CT (b = 0.0046, p = 0.035).
CONCLUSIONS: CT does not correlate with retinal sensitivity in AMD. Although
choroidal damage and impaired choroidal perfusion appear to be important concepts
in AMD pathogenesis, increasing choroidal thinning may not be associated with
worsening retinal function in AMD.
PMID- 28427082
TI - Perioperative Outcomes and Safety of Atrial Fibrillation Catheter Ablation in
Octogenarians: A Retrospective Study and Review of the Benefits of Rhythm
Control.
AB - OBJECTIVES: Catheter ablation for rhythm control has emerged as a successful
therapeutic option for the treatment of atrial fibrillation (AF), though it has
not been well studied in octogenarians. This study evaluates its safety in
octogenarians in a community hospital and reviews the benefits of rhythm control.
METHODS: Among 1,592 patients undergoing AF ablation, 84 octogenarian were
identified. The primary outcome was normal sinus rhythm (NSR) on
electrocardiogram at discharge. Secondary outcomes were periprocedural
complications and markers and risks of reablation compared to younger cohorts.
RESULTS: An NSR on discharge occurred in 83 patients. Three patients required
pacing for symptomatic sinus bradycardia, complete heart block, and symptomatic
junctional bradycardia, respectively. Reablation for recurrent AF occurred in 23
octogenarians. Using the octogenarians as reference, the relative risk (RR) of 1
reablation was not significantly different among the age groups 70-79, 60-69, and
<60 years. The RR of 2 reablations was greater in the octogenarian group (RR 0.26
[95% CI 0.09-0.71, p = 0.008], 0.42 [95% CI 0.17-1.04, p = 0.06], and 0.27 [95%
CI 0.1-0.75, p = 0.01], respectively). Coronary artery disease (OR 0.14, 95% CI
0.02-0.68, p = 0.026) and percutaneous coronary intervention (OR 0.13, 95% CI
0.02-0.63, p = 0.021) were markers for reablation. CONCLUSION: AF catheter
ablation achieved an NSR with minimal periprocedural complications. The benefits
of rhythm control should be considered in treatment.
PMID- 28427083
TI - Cumulative risk of breast cancer screening outcomes according to the presence of
previous benign breast disease and family history of breast cancer: supporting
personalised screening.
AB - BACKGROUND: Our aim was to assess the cumulative risk of false-positive screening
results, screen-detected cancer, and interval breast cancer in mammography
screening among women with and without a previous benign breast disease and a
family history of breast cancer. METHODS: The cohort included 42 928 women first
screened at the age of 50-51 years at three areas of the Spanish Screening
Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and
followed up until December 2012. We used discrete-time survival models to
estimate the cumulative risk of each screening outcome over 10 biennial screening
exams. RESULTS: The cumulative risk of false-positive results, screen-detected
breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a
previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family
history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous
benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women
without either of these antecedents, respectively. CONCLUSIONS: Women with a
benign breast disease or a family history of breast cancer had an increased
cumulative risk of favourable and unfavourable screening outcomes than women
without these characteristics. A family history of breast cancer did not increase
the cumulative risk of false-positive results. Identifying different risk
profiles among screening participants provides useful information to stratify
women according to their individualised risk when personalised screening
strategies are discussed.
PMID- 28427084
TI - Long-term improvement of breast cancer survivors' quality of life by a 2-week
group physical and educational intervention: 5-year update of the 'PACThe' trial.
AB - BACKGROUND: The advantages of adapted physical activity and nutritional education
(APANE) on breast cancer prognosis and quality of life (QoL) are well known, but
long-term results are lacking. METHODS: A randomised controlled trial testing a 2
week intervention in hydrothermal centres including APANE enrolled 251 patients
post-chemotherapy. QoL and weight control were significantly improved at 12
months. A 5-year follow-up was performed to evaluate the persistence of
improvements. RESULTS: QoL increase (SF36) was persistent: effect-size at 2, 3, 4
and 5 years equalled respectively 0.27 (-0.01; 0.56), 0.28 (-0.02; 0.58), 0.41
(0.02; 0.81) and 0.45 (0.11; 0.80). Weight control observed after intervention
lasted 2 years: 2.7% decrease at 1 year (P=0.0085), 2.5% at 2 years (P=0.025);
and respectively for waist -2.4% (-3.6; -1.1) (P=0.000014) and -1.3% (-2.5; -0.1)
(P=0.0072). CONCLUSIONS: A 2-week intervention in hydrothermal centres performed
shortly after chemotherapy can durably improve breast cancer patients' QoL and
reduce weight.
PMID- 28427085
TI - Tumour invasiveness, the local and systemic environment and the basis of staging
systems in colorectal cancer.
AB - BACKGROUND: The present study aimed to examine the relationship between tumour
invasiveness (T stage), the local and systemic environment and cancer-specific
survival (CSS) of patients with primary operable colorectal cancer. METHODS: The
tumour microenvironment was examined using measures of the inflammatory
infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma
percentage (TSP) and tumour budding. The systemic inflammatory environment was
examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte
ratio (NLR). A 5-year CSS was examined. RESULTS: A total of 331 patients were
included. Increasing T stage was associated with colonic primary, N stage, poor
differentiation, margin involvement and venous invasion (P<0.05). T stage was
significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP
(P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In
patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas
Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%,
respectively. The Glasgow Microenvironment Score, a score based on KM grade and
TSP, stratified survival from 93 to 58%. CONCLUSIONS: Although associated with
increasing T stage, local and systemic tumour environment characteristics, and in
particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants
of survival and may be utilised in the staging of patients with primary operable
colorectal cancer.
PMID- 28427086
TI - Self-sampling to improve cervical cancer screening coverage in Switzerland: a
randomised controlled trial.
AB - BACKGROUND: The aim of this study is to evaluate whether self-sampling can
increase screening attendance of women who do not attend regular screening in
Switzerland. METHODS: Participants were proactively recruited in Geneva between
September 2011 and November 2015. Women (25-69 years) who had not undergone CC
screening in the last 3 years were considered eligible. Through a 1 : 1 ratio
randomisation, enrolled participants were invited to either undergo liquid-based
cytology, which was performed by a health-care provider (control group, CG) or to
take a self-sample for HPV-testing, which was mailed to their home (intervention
group, IG). RESULTS: A total of 331 and 336 women were randomised in the CG and
in the IG, respectively. Overall, 7.3% (95% CI: 4.9-10.6) women in the CG and
5.7% (95% CI: 3.6-8.7) women in the IG did not undergo the initial screening
(P=0.400). There were 1.95% (95% CI: 0.8-4.3) women in the CG and 5.05% (95% CI:
3.1-8.1) women in the IG with a positive screen who did not attend triage and
colposcopy (P=0.036). CONCLUSIONS: The participation in CC screening in women
offered self-sampling was not higher than among those offered specimen collection
by a clinician. Compliance with further follow-up for women with a positive HPV
test on the self-sample requires further attention.
PMID- 28427087
TI - Pretreatment serum uracil concentration as a predictor of severe and fatal
fluoropyrimidine-associated toxicity.
AB - BACKGROUND: We investigated the predictive value of dihydropyrimidine
dehydrogenase (DPD) phenotype, measured as pretreatment serum uracil and
dihydrouracil concentrations, for severe as well as fatal fluoropyrimidine
associated toxicity in 550 patients treated previously with fluoropyrimidines
during a prospective multicenter study. METHODS: Pretreatment serum
concentrations of uracil and dihydrouracil were measured using a validated LC
MS/MS method. The primary endpoint of this analysis was global (any) severe
fluoropyrimidine-associated toxicity, that is, grade ?3 toxicity according to the
NCI CTC-AE v3.0, occurring during the first cycle of treatment. The predictive
value of uracil and the uracil/dihydrouracil ratio for early severe
fluoropyrimidine-associated toxicity were compared. Pharmacogenetic variants in
DPYD (c.2846A>T, c.1679T>G, c.1129-5923C>G, and c.1601G>A) and TYMS (TYMS 5'-UTR
VNTR and TYMS 3'-UTR 6-bp ins/del) were measured and tested for associations with
severe fluoropyrimidine-associated toxicity to compare predictive value with DPD
phenotype. The Benjamini-Hochberg false discovery rate method was used to control
for type I errors at level q<0.050 (corresponding to P<0.010). RESULTS: Uracil
was superior to the dihydrouracil/uracil ratio as a predictor of severe toxicity.
High pretreatment uracil concentrations (>16 ng ml-1) were strongly associated
with global severe toxicity (OR 5.3, P=0.009), severe gastrointestinal toxicity
(OR 33.7, P<0.0001), toxicity-related hospitalisation (OR 16.9, P<0.0001), as
well as fatal treatment-related toxicity (OR 44.8, P=0.001). None of the DPYD
variants alone, or TYMS variants alone, were associated with severe toxicity.
CONCLUSIONS: High pretreatment uracil concentration was strongly predictive of
severe, including fatal, fluoropyrimidine-associated toxicity, and is a highly
promising phenotypic marker to identify patients at risk of severe
fluoropyrimidine-associated toxicity.
PMID- 28427089
TI - Editor's Highlight: Exposure to CrVI during Early Pregnancy Increases Oxidative
Stress and Disrupts the Expression of Antioxidant Proteins in Placental
Compartments.
AB - Epidemiologic studies document relationships between chromium VI (CrVI) exposure
and increased risk of spontaneous abortion, stillbirth, preterm birth, and
neonatal death in pregnant women. Environmental contamination with CrVI is a
growing problem both in the United States and developing countries. CrVI is
widely used in numerous industries. This study was designed to understand the
mechanism of CrVI toxicity on placental oxidative stress and antioxidant (AOX)
machinery. Pregnant mother rats were treated with or without CrVI (50 ppm
K2Cr2O7) through drinking water from gestational day (GD) 9.5-14.5, and placentas
were analyzed on GD 18.5. Results indicated that CrVI reduced the trophoblast
cell population. CrVI increased reactive oxygen species (ROS) and decreased the
expression of AOX proteins. CrVI disrupts the trophoblast proliferation of the
placenta. This study provides insight into the critical role of AOXs in placental
function.
PMID- 28427088
TI - A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with
MGMT promoter methylation.
AB - BACKGROUND: Presently, few options are available for refractory colorectal cancer
(CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a
frequent and early event in CRC tumourigenesis. This epigenetic silencing is a
predictor of response to the alkylating drug temozolomide in glioblastoma.
Preclinical evidences and some case reports showed temozolomide activity in CRC
with MGMT silencing, but the available data from clinical trials are
inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according
to a two-stage Simon's optimal design to investigate activity and safety of
temozolomide in refractory CRC harbouring MGMT promoter methylation. The primary
end point was overall response rate (ORR). Patients who failed two or more prior
treatments received temozolomide at a dose of 150-200 mg m-2 per day on days 1-5
every 28 days. RESULTS: From July 2012 to June 2016, 225 patients were screened,
80 showed MGMT promoter methylation and 41 were enrolled. Overall response rate
was 10% and disease control rate was 32%. Median progression-free survival and
overall survival were 1.9 and 5.1 months, respectively. CONCLUSIONS: Temozolomide
showed a modest activity in this heavily pretreated population and the study did
not meet its primary end point. The role of temozolomide in CRC remains still
controversial and further research is warranted.
PMID- 28427090
TI - The Aldosterone Synthase Inhibitor FAD286 is Suitable for Lowering Aldosterone
Levels in ZDF Rats but not in db/db Mice.
AB - Inhibition of aldosterone synthase is an alternative treatment option to
mineralocorticoid receptor antagonism to prevent harmful aldosterone actions.
FAD286 is one of the best characterized aldosterone synthase inhibitors to date.
FAD286 improves glucose tolerance and increases glucose-stimulated insulin
secretion in obese and diabetic ZDF rats. However, there is limited knowledge
about the dose-dependent effects of FAD286 on plasma aldosterone, corticosterone,
and 11-deoxycorticosterone in ZDF rats and in db/db mice, a second important
rodent model of obesity and type 2 diabetes. In addition, effects of FAD286 on
plasma steroids in mice and rats are controversial. Therefore, obese Zucker
diabetic fatty (ZDF) rats and db/db mice were treated with FAD286 for up to 15
weeks and plasma steroids were evaluated using highly sensitive liquid
chromatography-tandem mass spectrometry. In ZDF rats, FAD286 (10 mg/kg/d)
treatment resulted in nearly complete disappearance of plasma aldosterone while
corticosterone levels remained unaffected and those of 11-deoxycorticosterone
were increased ~4-fold compared to vehicle control. A lower dose of FAD286 (3
mg/kg/d) showed no effect on plasma aldosterone or corticosterone, but 11
deoxycorticosterone was again increased ~4-fold compared to control. In contrast
to ZDF rats, a high dose of FAD286 (40 mg/kg/d) did not affect plasma aldosterone
levels in db/db mice although 11-deoxycorticosterone increased ~2.5-fold. A low
dose of FAD286 (10 mg/kg/d) increased plasma aldosterone without affecting
corticosterone or 11-deoxycorticosterone. In conclusion, the aldosterone synthase
inhibitor, FAD286, lowers plasma aldosterone in obese ZDF rats, but not in obese
db/db mice.
PMID- 28427091
TI - [Development and Evaluation of herzwegweiser.de - An Informational Website
designed for Post-Rehabilitation Support of Cardiac Patients and their Healthcare
Professionals in Berlin-Brandenburg].
AB - The internet portal 'herzwegweiser.de' was developed to assist individuals with
cardiovascular diseases in the phase III rehabilitation in the region of Berlin
Brandenburg. It provides information on this specific disease as well as on
aftercare services, e. g. regional cardiac groups. For the medical and
therapeutic colleagues specific information such as treatment guidelines and a
cardiac group placement service for trainers and medical doctors were set up. The
study was based on a mixed-methods design. Initially, structured interviews were
conducted to identify the expectations and needs of the internet portal. After
implementation of the portal, a partially standardized written survey was used to
evaluate its acceptance and usability. 105 former rehab patients and 42 medical
colleagues participated. The evaluation of the questionnaires was carried out
with frequency distributions, mean comparisons and Chi-square tests. The site was
rated with an overall high approval rating. Over 90% of the former rehab patients
rated content, structure, design, and the search function of the portal positive
as did more than 85% of the medical colleagues. 97% of the former rehab patients
and 95% professionals would recommend 'herzwegweiser.de'. This internet portal
can serve as a model for other regions and possibly other diseases.
PMID- 28427092
TI - Erratum: Pulmonary Embolism and Atrial Fibrillation: Two Sides of the Same Coin?
A Systematic Review.
PMID- 28427093
TI - Video-Assisted Thoracic Surgical Right Upper Lobectomy with Bronchus-First and
Simultaneous Vessel Stapling Technique.
AB - A method of video-assisted thoracic surgical (VATS) right upper lobectomy with
bronchus-first and simultaneous vessel stapling will be introduced. In this
study, all cases underwent two-port VATS as follows: first, the right upper lobe
bronchus was identified and stapled; then, all right upper lobe vessels were
stapled simultaneously. This method was performed in 50 cases. There was no
surgical mortality, hemorrhage, vascular injuries, or conversion. This technique
can reduce wound size and operative time and make the operation safer and easier
to accomplish.
PMID- 28427094
TI - Statin Therapy in Patients Undergoing Coronary Artery Bypass Grafting for Acute
Coronary Syndrome.
AB - BACKGROUND: This study evaluates whether preoperative statin therapy improves
clinical outcomes in patients referred to coronary artery bypass grafting (CABG)
for acute coronary syndrome (ACS). METHODS: A total of 1,151 patients undergoing
CABG for ACS were prospectively entered into the North-Rhine-Westphalia surgical
myocardial infarction registry and subdivided into two groups according to their
preoperative statin status (statin naive vs. statin group). A logistic regression
model was employed to analyze the impact of a statin therapy and dose for the
endpoints in-hospital mortality and major adverse cardiac events (MACE). RESULTS:
Demographics, pre- and intraoperative data of the statin-naive group (n = 208;
18%) and statin-treated group (n = 943, 82%) did not differ. In-hospital
mortality (12.6 vs. 6.3%, p = 0.002) and MACE rates (22.1 vs. 9.7%, p < 0.001)
were significantly higher in statin naive when compared with statin-treated
patients with ACS, respectively. Mevalonic acid revealed that both low- and high
dose statin treatment was associated to a reduction in in-hospital mortality and
MACE, without a dose-dependent statin effect. CONCLUSION: Statin therapy in
patients with ACS undergoing CABG reduces in a dose-independent manner in
hospital mortality and MACE.
PMID- 28427095
TI - Performance of Endocarditis-Specific Risk Scores in Surgery for Infective
Endocarditis.
AB - BACKGROUND: Risk models can play an important part in the decision-making of
surgery for infective endocarditis, but they remain underutilized. Several
endocarditis-specific risk models have been recently published with the aim to
improve on existing general cardiac surgery scores such as EuroSCORE. We compared
their prognostic utility of mortality and morbidities for infective endocarditis
surgery. METHODS: The additive Society of Thoracic Surgeon's (STS) Endocarditis
score, Costa score, De Feo-Cotrufo score, and Pulsuse score were calculated for
consecutive patients undergoing cardiac surgery for active infective endocarditis
during 2005 to 2011 at Auckland City Hospital and their discriminative value for
adverse outcomes assessed. RESULTS: Mean scores for 146 endocarditis surgery
patients with operative mortality 6.8% (10) were additive STS score: 32.2 +/-
13.5, Costa score: 12.0 +/- 6.8, De Feo-Cotrufo score: 14.6 +/- 9.2, and Pulsuse
score 2.2 +/- 1.3. Areas under curve and 95% confidence intervals for operative
mortality were 0.699 (0.534-0.865), 0.596 (0.426-0.765), 0.744 (0.590-0.899), and
0.673 (0.510-0.836), respectively. All four scores could also discriminate
mortality during follow-up and composite morbidity, with the De Feo-Cotrufo score
having the best overall performance. CONCLUSION: Endocarditis-specific risk
models had moderate discrimination of operative mortality and most postoperative
complications, and the De Feo-Cotrufo score is the preferred score to advise
clinical decisions in this setting.
PMID- 28427096
TI - PDE 2015: cAMP Signaling, Protein Kinase A (PKA) and Phosphodiesterases (PDEs):
How Genetics Changed the Way We Look at One of the Most Studied Signaling
Pathways.
PMID- 28427097
TI - Systematic Quantification of GPCR/cAMP-Controlled Protein Kinase A Interactions.
AB - The diffusible second messenger cyclic AMP (cAMP) originates from multiple G
protein-coupled receptor (GPCR) cascades activating the intracellular key
effector protein kinase A (PKA). Spatially and temporally restricted cAMP-fluxes
are directly sensed by macromolecular PKA complexes. The consequences are
alterations of molecular interactions, which lead to activation of
compartmentalized PKA phosphotransferase activities, regulating a vast array of
cellular functions. To decode cell-type and cell-compartment specific PKA
functions, the spatio-temporal dynamics of small molecule:protein interactions,
protein:protein interactions (PPIs), cAMP-mobilization, and phosphotransferase
activities need to be determined directly in the appropriate cellular context. A
collection of cell-based reporters has been developed to either visualize or
quantitatively measure kinase activities or PKA complex formation/dissociation.
In this review, we list a collection of unimolecular and bimolecular PKA
biosensors, followed by the specification of the modular design of a Renilla
luciferase based protein-fragment complementation assay (PCA) platform for
measuring PKA network interactions. We discuss the application spectrum of the
PCA reporter to identify, quantify, and dissect dynamic and transient PKA
complexes downstream of specific GPCR activities. We specify the implementation
of a PCA PKA platform to systematically quantify the concurrent involvement of
receptor-cAMP signaling, post-translational modifications, and kinase subunit
mutations/perturbations in PKA activation. The systematic quantification of
transient PKA network interactions will contribute to a better understanding how
GPCR-recognized input signals are streamlined through the compartmentalized and
cAMP-interacting PKA signalosome.
PMID- 28427098
TI - OPA1 in Lipid Metabolism: Function of OPA1 in Lipolysis and Thermogenesis of
Adipocytes.
AB - OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of
mitochondria. It was recently also shown to locate on lipid droplets in
adipocytes where it functions as an A-kinase anchoring protein (AKAP) that
mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of
perilipin (Plin1). In brown adipocytes indirect evidence support the notion that
OPA1 regulation of fission serves to increase thermogenesis, which thereby
contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid
droplets serves as a gatekeeper to control lipolysis induced by adrenergic
agonists. However, the function of OPA1 in lipolysis and thermogenesis in
inducible brown adipocytes (brite/beige cells) remains elusive. Here we discuss
the role of OPA1 in lipid metabolism.
PMID- 28427099
TI - Role of Phosphodiesterases on the Function of Aryl Hydrocarbon Receptor
Interacting Protein (AIP) in the Pituitary Gland and on the Evaluation of AIP
Gene Variants.
AB - Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by
loss-of-function germline mutations in the AIP gene. Patients harboring AIP
mutations usually present with somatotropinomas resulting either in gigantism or
young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor
suppressor properties in somatotroph cells. Among other mechanisms proposed to
explain this function, a regulatory effect over the 3',5'-cyclic adenosine
monophosphate (cAMP) signaling pathway seems to play a prominent role. In this
setting, the well-known interaction between AIP and 2 different isoforms of
phosphodiesterases (PDEs), PDE2A3 and PDE4A5, is of particular interest. While
the interaction with over-expressed AIP does not seem to affect PDE2A3 function,
the reported effect on PDE4A5 is, in contrast, reduced enzymatic activity. In
this review, we explore the possible implications of these molecular interactions
for the function of somatotroph cells. In particular, we discuss how both PDEs
and AIP could act as negative regulators of the cAMP pathway in the pituitary,
probably both by shared and independent mechanisms. Moreover, we describe how the
evaluation of the AIP-PDE4A5 interaction has proven to be a useful tool for
testing AIP mutations, complementing other in silico, in vitro, and in vivo
analyses. Improved assessment of the pathogenicity of AIP mutations is indeed
paramount to provide adequate guidance for genetic counseling and clinical
screening in AIP mutation carriers, which can lead to prospective diagnosis of
pituitary adenomas.
PMID- 28427100
TI - Dystrophinopathies and Limb-Girdle Muscular Dystrophies.
AB - Muscular dystrophies are a heterogeneous group of inherited diseases. The natural
history of these disorders along with their management have changed mainly due to
a better understanding of their pathophysiology, the evolution of standards of
care, and new treatment options. Dystrophinopathies include both Duchenne's and
Becker's muscular dystrophies, but in reality they are a spectrum of muscle
diseases caused by mutations in the gene that encodes the protein dystrophin.
Duchenne's muscular dystrophy is the most common form of inherited muscle disease
of childhood. The current standards of care considerably prolong independent
ambulation and survival. Several therapeutic options either aiming at
substituting/correcting the primary protein defect or limiting the progression of
the dystrophic process are currently being explored in clinical trials.Limb
girdle muscular dystrophies (LGMDs) are rare and heterogeneous conditions,
characterized by weakness and wasting of the pelvic and shoulder girdle muscles.
Originally classified into dominant and recessive, > 30 genetic forms of LGMDs
are currently recognized. Further understanding of the pathogenic mechanisms of
LGMD will help identifying novel therapeutic approaches that can be tested in
clinical trials.
PMID- 28427101
TI - Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats.
AB - Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In
this study, we aimed to investigate whether tanshinol has potential therapeutic
effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced
myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five
groups: a control group, a model group, and three model groups treated with 25 or
50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone
acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards,
all animals underwent a surgical procedure to induce bone defects at the right
proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or
calcitriol treatment was continued to the endpoint. At the experimental endpoint,
compared to the model group, 25 mg/kg tanshinol could significantly reverse
glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing
mechanical bone strength, causing a significant 11 % increase in trabecular
number, and reducing trabecular separation by 28 %. In addition, tanshinol
improved the bone microarchitecture and prevented glucocorticoid-induced bone
loss by promoting bone formation and inhibiting bone resorption. Moreover,
results of bone defect repair and muscle weight measurements revealed that
tanshinol accelerated the bone fracture healing process and attenuated muscle
atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold
upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold
increases in vascular endothelial growth factor mRNA expression in calluses from
the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels
from glucocorticoid-induced elevation. These findings demonstrate the potential
benefits of tanshinol against glucocorticoid-induced osteoporosis and
glucocorticoid-induced myopathy, which warrants further investigation in future
studies.
PMID- 28427102
TI - An Intramolecular CAr-H***O=C Hydrogen Bond and the Configuration of Rotenoids.
AB - Over the past half a century, the structure and configuration of the rotenoids, a
group of natural products showing multiple promising bioactivities, have been
established by interpretation of their NMR and electronic circular dichroism
spectra and confirmed by analysis of single-crystal X-ray diffraction data. The
chemical shift of the H-6' 1H NMR resonance has been found to be an indicator of
either a cis or trans C/D ring system. In the present study, four structures
representing the central rings of a cis-, a trans-, a dehydro-, and an oxadehydro
rotenoid have been plotted using the Mercury program based on X-ray crystal
structures reported previously, with the conformations of the C/D ring system,
the local bond lengths or interatomic distances, hydrogen bond angles, and the H
6' chemical shift of these compounds presented. It is shown for the first time
that a trans-fused C/D ring system of rotenoids is preferred for the formation of
a potential intramolecular C6'-H6'***O=C4 H-bond, and that such H-bonding results
in the 1H NMR resonance for H-6' being shifted downfield.
PMID- 28427103
TI - Saffron Flower Extract Promotes Scratch Wound Closure of Keratinocytes and
Enhances VEGF Production.
AB - During saffron (Crocus sativus) spice production, large amounts of floral
biowaste are generated. It was the aim of this study to develop a value-added
product from saffron floral biowaste to be used as a natural cosmetic ingredient.
HPLC-PDA-MS analysis of saffron flower extracts revealed the presence of
flavonols with the highest amounts in the acetone extract. Kaempferol-3-O
sophoroside was identified as the main flavonoid in the acetone extract (saffron
flower acetone extract). Saffron flower acetone extract and kaempferol-3-O
sophoroside were tested in HaCaT cells for potential effects on cell migration,
proliferation, and for anti-inflammatory properties. Saffron flower acetone
extract concentration dependently (50-200 ug/mL) augmented cell proliferation, as
indicated by an increased BrdU-incorporation, while kaempferol-3-O-sophoroside (1
50 uM) had no effect. Furthermore, treatment of HaCaT cells with saffron flower
acetone extract, but not with kaempferol-3-O-sophoroside, concentration
dependently increased vascular endothelial growth factor secretion (control 49.72
pg/mL vs. saffron flower acetone extract at 200 ug/mL 218.60 pg/mL). Cell
migration was determined using time-lapse microscopy and a modification of the
scratch-wound assay in which saffron flower acetone extract significantly
improved wound closure compared to the untreated control. Overproduction of the
proinflammatory cytokines interleukin-8 and interleukin-6 in HaCaT cells was
induced by TNF-alpha. Kaempferol-3-O-sophoroside (10-50 uM), but not saffron
flower acetone extract, inhibited TNF-alpha-induced IL-8 secretion. The effect
was comparable to 10 uM hydrocortisone (positive control). Interestingly, saffron
flower acetone extract further increased IL-6 levels in TNF-alpha-treated HaCaT
cells in a concentration-dependent manner. In summary, the pronounced wound
healing properties of saffron flower acetone extract present a promising
application for the cosmetic industry.
PMID- 28427104
TI - Pharmacokinetics and Pharmacodynamics of Tofogliflozin (a Selective SGLT2
Inhibitor) in Healthy Male Subjects.
AB - Tofogliflozin is a selective oral inhibitor of sodium-glucose co-transporter 2
for treatment of type 2 diabetes mellitus. The pharmacokinetics,
pharmacodynamics, and safety of tofogliflozin were investigated in healthy male
subjects. Three studies were conducted: single-ascending dose study (10-640 mg)
in 56 Japanese and 24 Caucasian subjects; multiple-ascending dose study (2.5-80
mg once daily for 7 days) in 24 Japanese subjects; and food-effect study (20-40
mg) in 30 Japanese subjects. Tofogliflozin was absorbed rapidly and eliminated
from the systemic circulation with a t1/2 of 5-6 h. Exposure increased dose
proportionally up to 320 mg. Body weight-corrected exposure was similar between
Japanese and Caucasian subjects. Urinary excretion of tofogliflozin ranged from
17.1 to 27.4% of dose. Tofogliflozin did not accumulate with once daily
administration. Food intake decreased Cmax by approximately 30% but did not
change AUC0-inf. Tofogliflozin caused dose-dependent daily urinary glucose
excretion (UGE0-24h), but food intake condition at administration did not affect
it. The exposure-response relationship between plasma average concentration of
tofogliflozin (Cavg) and UGE0-24h fitted Emax model well. There were no serious
adverse events leading to discontinuation or episodes of hypoglycemia. Single and
multiple administration of tofogliflozin were generally well tolerated. Exposure
to tofogliflozin was dose-proportional up to 320 mg and did not accumulate with
multiple once-a-day administration. The model suggests more than 100 ng/mL Cavg
corresponding to the dose of between 20 and 40 mg leads to almost maximum effect
of tofogliflozin.
PMID- 28427105
TI - Optimizing Outcomes in Free Flap Breast Reconstruction in the Community Hospital
Setting: A Stepwise Approach to DIEP/SIEA Flap Procedures with Banking a
Hemiabdominal Flap.
PMID- 28427106
TI - Lateral Ventricle to Sylvian Fissure Shunt for Obstructive Hydrocephalus: First
Report.
AB - Cerebrospinal fluid (CSF) pathway studies have revealed that the CSF secreted
from the choroid plexus of the ventricles after egressing from the fourth
ventricle reaches the basal suprasellar cistern and ultimately the sylvian
cisterns. From the sylvian cistern, the CSF travels over the cerebral convexity
subarachnoid space to reach the superior sagittal sinus and enters the
bloodstream. Diverting CSF from the lateral ventricle with a shunt catheter to
the sylvian cistern can be an option to treat obstructive hydrocephalus. An adult
patient with posttraumatic hydrocephalus with contraindications to
ventriculoperitoneal and ventriculoatrial shunt placement underwent this
procedure of diverting CSF from the lateral ventricle to the sylvian cistern
successfully, and he had immediate relief of symptoms of raised intracranial
pressure. Although preliminary results seem logical and promising, more cases and
longer follow-up is required to consider this shunt operation an option in the
treatment of obstructive hydrocephalus.
PMID- 28427107
TI - ?
PMID- 28427108
TI - An unusual hypoechoic solid mass in the pancreatic head.
AB - Solid pancreatic lesions found on imaging procedures are suspicious for
malignancy and, therefore, demand immediate diagnostic evaluation and therapy. In
the case of indeterminate histology, a primary resection should be considered in
order to preserve the possibility of curative surgery, although rare entities may
be initially disregarded. We present here the case of a 48-year-old female
patient with a hypoechoic lesion of the pancreatic head, which was clearly
delineated from the surrounding pancreatic tissue. The challenging diagnosis of
metastatic leiomyosarcoma could only be established by considering the long-term
clinical history and former histology specimens.
PMID- 28427109
TI - Traveler's Diarrhea, vision abnormalities and unsteady gait in a young woman.
AB - We report on the course of disease in a young woman, originally admitted with
suspected refractory infectious tropical traveler's diarrhea. However, symptoms
did not resolve upon either symptomatic or subsequent antibiotic therapy. When
neurologic deterioration was observed, imaging studies revealed a dramatic series
of thromboembolic events, including intracranial hemorrhage caused by extensive
sinus vein thrombosis as well as thrombi of the right cardiac ventricle. Colonic
mucosal biopsy samples finally led to the histologic diagnosis of ulcerative
colitis. Having excluded thrombophilia or any other disease potentially related
to a prothrombotic state, we interpreted the thromboembolic events as secondary
to the primary manifestation of the underlying inflammatory bowel disease.The
increased risk of thromboembolic complications-especially deep vein thrombosis
and pulmonary embolism-in inflammatory bowel disease is well documented in the
literature. However, sinus vein thrombosis and cardiac thrombi represent a
remarkable dimension of this risk and a rare course of coagulopathy secondary to
an acute flare of ulcerative colitis. Still, there is a lack of awareness of this
risk, resulting in poor implementation of preventive measures modifying risk
factors and allowing for pharmacological prophylaxis. We therefore emphasize that
in line with the 2014 German S3 Guideline-thromboprophylaxis in the setting of an
acute flare of inflammatory bowel disease is mandatory and should not be
restricted because of safety concerns.
PMID- 28427110
TI - ?
PMID- 28427111
TI - [In-vitro activity of mecillinam against urine isolates of Escherichia coli from
outpatient departments in Germany].
AB - National and international guidelines recommend fosfomycin trometamol,
nitrofurantoin, nitroxoline, and pivmecillinam as first-line agents for the
treatment of acute uncomplicated cystitis. Escherichia coli is by far the leading
cause of community-acquired urinary tract infections. Pivmecillinam (X-SYSTO(r))
is an oral prodrug of mecillinam, a penicillin derivative that was reintroduced
to the German market in March 2016. This study aimed to investigate the
proportion of mecillinam-resistant strains among E. coli isolates prior to the
introduction of X-SYSTO(r) in Germany.An in-vitro study was carried out to
determine the minimal inhibitory concentrations (MICs) of mecillinam against 494
urine isolates of E. coli (including multidrug-resistant strains). Isolates were
obtained from outpatients and collected in 25 laboratories between October and
December 2013. MIC breakpoints defined by the European Committee on Antimicrobial
Susceptibility Testing (EUCAST) were applied for classifying the bacterial
isolates as mecillinam-susceptible (MIC <= 8 mg/l) or resistant (MIC > 8
mg/l).The concentrations of mecillinam needed to inhibit 50 % and 90 % of the
test isolates were 1 and 4 mg/l, respectively, for isolates displaying the
extended spectrum beta-lactamase phenotype, and 0.25 and 4 mg/l, respectively,
for the remaining isolates. Overall, 98 % of the isolates were found to be
mecillinam-susceptible (MIC <= 8 mg/l), and 2 % were found to be resistant (MIC >
8 mg/l).These findings support the recommendation to regard pivmecillinam as a
first-line option for the treatment of acute uncomplicated cystitis.
PMID- 28427112
TI - Acute encephalopathy in a 2-year-old pot-bellied pig following accidental
intoxication with clonazepam.
AB - OBJECTIVE: To describe a case of successful management of clonazepam toxicity
causing encephalopathy in a pot-bellied pig. CASE SUMMARY: A 2-year-old female
pot-bellied pig weighing 13.5 kg was presented for evaluation of clinical signs
of acute encephalopathy. Based on the animal's history and clinical signs, a
tentative diagnosis of benzodiazepine (BZP) intoxication was made. The results of
a urinary drug screening test designed to detect illicit substances in human
urine indicated benzodiazepine exposure. Gas chromatography and mass spectrometry
analysis later confirmed clonazepam (urinary concentration 496 ng/mL) as the
intoxicating substance. The pig responded favorably to treatment which included
administration of flumazenil, decontamination with enteral activated charcoal,
and intravenous isotonic crystalloid administration. The pig had a rapid
improvement in mentation 10 minutes following IV flumazenil administration and
was considered mentally appropriate following 24 hours of hospitalization. The
pig was discharged from the hospital after 48 hours of care, and was reported to
be doing well 6 months later. NEW INFORMATION PROVIDED: Intoxication with
prescription benzodiazepines can occur in companion animals and result in
clinical signs of acute encephalopathy. Urinary drug screening tests designed for
human use may provide rapid results to indicate drug intoxication and guide
therapeutic intervention in veterinary species. Administration of flumazenil
resulted in a rapid improvement in mentation following clonazepam intoxication in
a pot-bellied pig.
PMID- 28427113
TI - Simultaneous quantification and semi-quantification of amentoflavone and its
metabolites in human intestinal bacteria by liquid chromatography Orbitrap high
resolution mass spectrometry.
AB - A quick, easy, effective method followed by ultra-high-pressure liquid
chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry
(UHPLC-LTQ-Orbitrap MS) was developed for the simultaneous identification and
quantification of the metabolites produced by amentoflavone (AMF) in human
intestinal bacteria from human feces. The method validated for quantification of
AMF concerning precision, accuracy, recovery, matrix effect, stability and limits
showed acceptable results. Compared with blank human intestinal bacteria
chromatography, three metabolites were identified based on high-accuracy
protonated precursors and multi-stage mass spectrometry (MSn ) using the proposed
strategy. At the same time, a new method was developed for semi-quantification of
three metabolites. We describe the trend over 24 h of concentration-time curves
for AMF and its metabolites. Moreover, the main metabolic pathway of AMF was
clarified in human intestinal bacteria. The method was validated and successfully
applied to the detection and quantification of AMF and its metabolites.
PMID- 28427115
TI - Personality assessment and model comparison with behavioral data: A statistical
framework and empirical demonstration with bonobos (Pan paniscus).
AB - Interest in quantifying consistent among-individual variation in primate
behavior, also known as personality, has grown rapidly in recent decades.
Although behavioral coding is the most frequently utilized method for assessing
primate personality, limitations in current statistical practice prevent
researchers' from utilizing the full potential of their coding datasets. These
limitations include the use of extensive data aggregation, not modeling
biologically relevant sources of individual variance during repeatability
estimation, not partitioning between-individual (co)variance prior to modeling
personality structure, the misuse of principal component analysis, and an over
reliance upon exploratory statistical techniques to compare personality models
across populations, species, and data collection methods. In this paper, we
propose a statistical framework for primate personality research designed to
address these limitations. Our framework synthesizes recently developed mixed
effects modeling approaches for quantifying behavioral variation with an
information-theoretic model selection paradigm for confirmatory personality
research. After detailing a multi-step analytic procedure for personality
assessment and model comparison, we employ this framework to evaluate seven
models of personality structure in zoo-housed bonobos (Pan paniscus). We find
that differences between sexes, ages, zoos, time of observation, and social group
composition contributed to significant behavioral variance. Independently of
these factors, however, personality nonetheless accounted for a moderate to high
proportion of variance in average behavior across observational periods. A
personality structure derived from past rating research receives the strongest
support relative to our model set. This model suggests that personality variation
across the measured behavioral traits is best described by two correlated but
distinct dimensions reflecting individual differences in affiliation and
sociability (Agreeableness) as well as activity level, social play, and neophilia
toward non-threatening stimuli (Openness). These results underscore the utility
of our framework for quantifying personality in primates and facilitating greater
integration between the behavioral ecological and comparative psychological
approaches to personality research.
PMID- 28427114
TI - Lifestyle use of drugs by healthy people for enhancing cognition, creativity,
motivation and pleasure.
AB - Today, there is continued, and in some cases growing, availability of not only
psychoactive substances, including treatments for mental health disorders such as
cognitive enhancers, which can enhance or restore brain function, but also
'recreational' drugs such as novel psychoactive substances (NPS). The use of
psychoactive drugs has both benefits and risks: whilst new drugs to treat
cognitive symptoms in neuropsychiatric or neurodegenerative disorders could have
great benefits for many patient groups, the increasing ease of accessibility to
recreational NPS and the increasing lifestyle use of cognitive enhancers by
healthy people means that the effective management of psychoactive substances
will be an issue of increasing importance. Clearly, the potential benefits of
cognitive enhancers are large and increasingly relevant, particularly as the
population ages, and for this reason, we should continue to devote resources to
the development of cognitive enhancers as treatments for neurodegenerative
diseases and psychiatric disorders, including Alzheimer's disease, attention
deficit hyperactivity disorder and schizophrenia. However, the increasing use of
cognitive enhancers by healthy individuals raises safety, ethical and regulatory
concerns, which should not be ignored. Similarly, understanding the short- and
long-term consequences of the use of NPS, as well as better understanding the
motivations and profiles of users could promote more effective prevention and
harm reduction measures. Linked Articles This article is part of a themed section
on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the
other articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.
PMID- 28427117
TI - [Standardize the diagnosis and treatment of thyrotropin-secreting pituitary
tumors].
PMID- 28427116
TI - Current Trends in the Management of Gastroesophageal Reflux Disease.
AB - Gastroesophageal reflux disease (GERD) characterized by heartburn and/or
regurgitation symptoms is one of the most common gastrointestinal disorders
managed by gastroenterologists and primary care physicians. There has been an
increase in GERD prevalence, particularly in North America and East Asia. Over
the past three decades proton pump inhibitors (PPIs) have been the mainstay of
medical therapy for GERD. However, recently there has been an increasing
awareness amongst physicians and patients regarding the side effects of the PPI
class of drugs. In addition, there has been a marked decline in the utilization
of surgical fundoplication as well as a rise in the development of nonmedical
therapeutic modalities for GERD. This review focuses on different management
strategies for GERD, optimal management of refractory GERD with special focus on
available endoluminal therapies and the future directions.
PMID- 28427118
TI - [Strengthen multidisciplinary collaboration to enhance the level of diagnosis and
treatment of thyrotropin secreting adenoma].
PMID- 28427119
TI - [Genetic analysis of posterior cranial fossa morphology in families of Chiari
malformation type I].
AB - Objective: To explore genetic characteristic of posterior cranial fossa
morphology in families of Chiari malformation type I (CMI). Methods: From April
2010 to May 2016, a total of 47 cases of CMI families (CMI group) and their 94
parents (CMI-P group)collected were retrospectively reviewed in Department of
Spinal Surgery, Drum Tower Hospital, School of Medicine, Nanjing
University.Another cohort of 50 asymptomatic adults was enrolled to serve as the
control group.Patients with skull fracture or other diseases which can lead to
secondary CMI were excluded.On mid-sagittal T2-weighted magnetic resonance (MR)
imaging, four measurements were evaluated and compared between these three
groups, including the length of cerebellar tonsillar descent, the area of
posterior cranial fossa(PCF area), the area of the brain tissue in posterior
cranial fossa (PCF tissue area), and the PCF crowdedness indexes (PCF tissue
area/ PCF area*100%). Results: Totally 47 CMI patients (21 males and 26 females;
mean age, 16.4 years), 94 parents (47 males and 47 females; mean age, 39.2 years)
and 50 controls (23 males and 27 females; mean age, 22.3 years) were recruited in
this study.Significant differences in all four indexes were found between CMI
group and the control group.The length of cerebellar tonsillar descent were much
bigger in CMI-P group than in the control group (1.5+/-2.2 mm vs -0.9+/-1.1 mm),
with 7 cases reach the diagnostic criteria of Chiari malformation(>=5 mm) and one
with syingomyelia.Compared to the control group, CMI-P group had smaller PCF
area, and its PCF crowdedness indexes averaged 90.0% as between the control group
(85.3%) and the CMI group (93.6%). Conclusions: In CMI families, parents have
similar posterior cranial fossa abnormalities with their CMI children, presenting
obviously narrow and crowded.Their PCF crowdedness indexes are between normal
subjects and CMI patients, and their cerebellar tonsils are lower, even some
parents are also CMI patients, suggesting genetic mechanisms involved in the
development of CMI.
PMID- 28427120
TI - [Arthroscopic treatment of eldly with massive rotator cuff tear].
AB - Objective: To investigate the surgical technique and clinical efficacy of
arthroscopic treatment of the elderly patients with massive rotator cuff tear.
Methods: From June 2012 to June 2015, thirty-six patients with massive rotator
cuff tear were treated with arthroscopic and followed up. The visual analog
scale(VAS)pain score, University of California Los Angeles (UCLA) scores,
Constant scores and American Shoulder and Elbow Surgeons scale(ASES)were used
before and after the arthroscopic surgery. Results: All the patients were
followed up for average of 18.5 (12 to 30) months.Before arthroscopic surgery,
the VAS, UCLA, Constant, ASES were (6.1+/-2.2), (10.6+/-4.3), (40.3+/-10.5) and
(28.8+/-18.5) points; the average flexion of the shoulder was (76.5+/-42.6)
degrees , the average abduction of the shoulder was (72.4+/-35.2) degrees , the
average external rotation of the shoulder was(26.6+/-22.2) degrees and the
average internal rotation of the shoulder was (20.2+/-6.2) degrees
respectively.These scores were improved to (1.4+/-1.2), (30.4+/-5.2), (82.6+/
12.6), and (78.8+/-22.6) points, the average flexion of the shoulder was improved
to (152.8+/-25.6) degrees , the average abduction of the shoulder was improved to
(120.6+/-32.8) degrees , the average external rotation of the shoulder was
improved to (42.6+/-16.2) degrees and the average internal rotation of the
shoulder was improved to (38.4+/-5.6) degrees after one-year follow-up
period.Improvement in these scores and range of motion(ROM) were significant
difference(P<0.05). Conclusion: Arthroscopic repair can effectively treat the
eldly patient with massive rotator cuff tear and obviously improve the function
of shoulder joint. The surgery has a clinical application value.
PMID- 28427121
TI - [Efficacy and safety of vertebrae pedicle subtraction osteotomy by posterior
trans apical for correction of severe and rigid idiopathic scoIiosis].
AB - Objective: To evaluate the efficacy and safety of pedicle subtraction osteotomy
for correction of severe rigid idiopathic scoliosis. Methods: From January 2003
to December 2014, eighteen patients with severe rigid idiopathic scoliosis were
treated by posterior wedge osteotomy in department of spinal surgery, the First
Affiliated Hospital of Xinjiang Medical University. There were 5 males and 13
females, and the average age at was (16.9+/-9.1)years, and the average follow-up
was 47.6 months. The coronal and sagittal Cobb's angles, sagittal trunk shifts,
apical vertebral translation, height change and fusion segments were measured on
standing AP and lateral radiographs before, after surgery and the final follow
up. Results: The Cobb's angle in the coronal plane was corrected from (94.3+/
13.3) degrees to (31.6+/-14.8) degrees , representing 64.8% correction rate. The
Cobb's angle in the sagittal plane was corrected from (62.5+/-17.8) degrees to
(27.1+/-11.7) degrees , representing 82.6% correction rate. Coronal trunk shift
was obviously improved from -29.8 mm to -3.5 mm. the average fusion segments was
13.7+/-1.8 ranging from 11 to 17 segments. Perioperative complications consisted
of pleura injury in 4 cases, cerebrospinal fluid leakage in 2 cases transient
neurological damage in 2 cases and delayed infection in 1 case. Conclusion:
Pedicle Subtraction Osteotomy correction by the single posterior approach is a
reliable and safe surgical technique for correction of severe rigid idiopathic
scoliosis.
PMID- 28427122
TI - [Application on the quantitative perfusion parameters of dynamic contrast
enhanced MRI in the pathological subtype of uterine leiomyoma].
AB - Objective: To analyze the value of the quantitative perfusion parameters of
dynamic contrast-enhanced MRI(DCE-MRI) in the pathological subtype of uterine
leiomyoma. Methods: A total of 35 cases of uterine leiomyoma confirmed by surgery
and pathology were retrospectively analyzed in Shaoxing People's Hospital from
October 2015 to May 2016.All cases underwent DCE-MRI. Quantitative perfusion
parameters were prospectively measured and analyzed, including transfer constant
(K(trans)) , efflux rate constant (K(ep)), extravascular extracellular space
volume ratio (V(e)), blood plasma volume ratio (V(p)), permeability surface area
product (PS) and plasma flow (F(p)) , using signal-input two-compartment tracer
kinetic models (Extended Tofts model and Exchange model) in 35 leiomyoma
cases.After the operation, the 35 cases were divided into three groups according
to the pathological classfication , the ordinary, the cellular and the
degeneration type.To analyze the differences among the three groups about the
quantitative perfusion parameters of uterine leiomyoma. Compared with the gold
standard of pathological findings, the ROC curves were drawn to evaluate the
diagnostic efficacy of different quantitative perfusion parameters. Results: In
the ordinary, cellular and degeneration type of uterine leiomyoma, K(trans) value
were respectively(0.684+/-0.341), (1.897+/-0.458), (0.554+/-0.514)/min; K(ep)
were respectively(1.004+/-0.685), (2.362+/-1.001), (1.274+/-1.093)/min; V(e) were
respectively 0.789%+/-0.186%, 0.806%+/-0.203%, 0.537%+/-0.314%; V(p) were
respectively 0.145%+/-0.196%, 0.502%+/-0.338%, 0.062%+/-0.106% and F(p) were
respectively(0.792+/-0.461), (2.426+/-0.509), (0.628+/-0.551)ml/min.Among three
groups, the value of K(trans), K(ep), V(e), V(p) and F(p) had statistical
difference(all P<0.05), the value of PS didn't have statistical difference. The
value of K(trans), K(ep), V(p) and F(p) in cellular type were higher than the
ordinary type(all P<0.01); the value of K(trans), V(p) and F(p) in cellular type
were higher than the degeneration type(all P<0.01); the value of V(e) in ordinary
type was higher than the degeneration type(P<0.05). The area under ROC curve was
0.981 for K(trans), 0.904 for K(ep), 0.622 for V(e), 0.840 for V(p) and 0.994 for
F(p). Conclusion: The quantitative perfusion parameters of DCE-MRI , especially
the value of K(trans), K(ep), V(p) and F(p) have a great diagnostic efficacy in
the pathological classfication of uterine leiomyoma which will become a
predictive factor of pathological classfication in uterine leiomyoma.
PMID- 28427123
TI - [Predictive value of liver pathologic changes in determining the effectiveness of
entecavir treatment for chronic hepatitis B-An analysis of 1 366 cases].
AB - Objective: To analyze the relationship between baseline liver pathologic changes
and the effectiveness of entecavir(ETV) and investigate the predictive value of
baseline liver pathologic changes in determining the effectiveness of ETV, to
provide reliable basis for precision medicine in patients with chronic hepatitis
B(CHB). Methods: A total of 1 366 cases with CHB were retrospectively recruited
who underwent liver biopsy between January 2006 to June 2016 and were treated
with ETV over 96 weeks.The relationship between baseline liver pathologic changes
and the antiviral responses to ETV at 48, 96 weeks were compared. Results: Liver
pathology was employed to make the definite inflammation grade and the fibrosis
stage.According to the liver inflammation and fibrosis, patients were divided
into 4 groups(G1, G2, G3, G4 and S1, S2, S3, S4 respectively). The complete
response rate of G1, G2, G3 and G4 after 48 weeks ETV treatment was 26.3%(10/38),
30.9%(121/391), 35.3%(101/286), 44.4%(52/117) respectively in HBeAg positive
patients and was 61.5%(24/39), 80.4%(148/184), 82.4%(201/244), 88.1%(59/67)
respectively in HBeAg negative patients.There was statistical difference in the
complete response rates among liver inflammation grades both in HBeAg positive
patients(chi(2)=8.510, P<0.05) and in HBeAg negative patients(chi(2)=12.054,
P<0.05)respectively.The differences were still statistical significant after 96
weeks ETV treatment (P<0.05). The complete response rates of S1, S2, S3 and S4
after 48 weeks ETV treatment were 39.0%(41/105), 37.8%(127/336), 30.9%(97/314),
24.7%(19/77), respectively in HBeAg positive patients and was 85.7%(30/35),
84.4%(92/109), 83.9%(162/193), 75.1%(148/197) respectively in HBeAg negative
patients. Whether HBeAg was positive or not, the rates were in decline but there
was no statistical difference in the complete response rates among liver fibrosis
stages(chi(2)=7.765, P>0.05; chi(2)=6.729, P>0.05). The differences were still
not statistical significant after 96 weeks ETV treatment (P>0.05). But after
further grouping, whether HBeAg was positive or not, as the degree of fibrosis
stage was aggravating, the complete response rate of G2, G3 and G4 after 48 weeks
ETV treatment decreased at the same degree of inflammation grade and the
differences were statistically significant (P<0.05). The differences were still
statistical significant after 96 weeks ETV treatment (P<0.05). Conclusions: The
responses to ETV treatment are closely related with baseline liver pathology.The
CHB patients with higher score of inflammation and lower score of fibrosis will
have a good response to ETV treatment.The degree of inflammation grades and
fibrosis stages can be used as early predictors of ETV treatment for CHB.
PMID- 28427124
TI - [Contemporary use of ticagrelor in patients with acute coronary syndrome after
discharge].
AB - Objective: To investigate the degree and determinants of using ticagrelor among
discharged patients with acute coronary syndrome (ACS). Methods: Patients with
ACS in Fuwai hospital who were given ticagrelor after discharge between Jan. 2015
to Jun. 2015 were analyzed.The clinical characteristics and adherence to
ticagrelor of these patients were collected by reviewing the electronic medical
records and telephone interview.Date were statistically-analyzed. Results: Among
all screened 404 patients, 158 (39.1%) patients prematurely stopped ticagrelor
within 12 months, while 119(29.5%) patients switched from ticagrelor to
clopidogrel.Unavailable locally (34.8%), economic reasons (17.7%) and hemorrhagic
events (18.4%) were the main causes of the premature discontinuation of
ticagrelor.Univariate analysis showed left main disease (P=0.04) and the
frequency of outpatient follow-up (P<0.01) as relative factors for prematurely
stopping ticagrelor outside hospital after discharge.Multivariate analysis
revealed medical insurance payment (OR 1.79, 95%CI 1.03-3.11) and the frequency
of outpatient follow-up (OR 0.61, 95%CI 0.43-0.86) as independent predictors of
prematurely stopping ticagrelor outside hospital.Prematurely stopping ticagrelor
has no significant effect on the ischemic events (myocardial infaction or stroke)
(P=0.76). Conclusion: Social cinditions is the main factor for the persistence to
ticagrelor among ACS patients after dischcrge.Medical insurance payment and low
frequency of outpatient follow-up were independent predictors of prematurely
stopping ticagrelor and it may not have impact on ischemic events.
PMID- 28427126
TI - [Patency rate of autogenous arteriovenous fistula after repairment in the
patients with late fistula dysfunction/faliure].
AB - Objective: To invesitigate 3-year patency rate of autogenous arteriovenous
fistula(AVF)in the patients with late fistula dysfunction/failure. Methods: The
prospective study was carried out in the First Hospital of Tsinghua University
from March 2012 to March 2013. A total of 136 maintenance hemodialysis patients
with late AVF dysfunction/faliure who received AVF repairment were enrolled in
the study. All the patients were divided into three groups according to surgical
procedures: venous neointimal hyperplasia (VNH) stripping group (group A), non
VNH stripping group (group B) and creation of a new AVF group (group C). Patency
rate was calculated by survival analysis method, and survival curve of fistula
was drawn as well. Results: During 12-36 months follow-up, there were 46 patients
with late AVF dysfunction/faliure in group A, 38 patients in group B, and 52
pateints in group C. The AVF patency rate was 88.6% at 12th month, 77.6% at 24th
month, and 57.2% at 36th month in group A; 89.3% at 12th month, 74.5% at 24th
month, and 55.1% at 36th month in group B; 88.1% at 12th month, 76.8% at 24th
month, and 59.0% at 36th month in group C. The AVF patency rates had no
statistical difference among three groups at three time points (12th, 24th and
36th month) (P>0.05). Conclusion: The patency rate was high in the patients who
recieved AVF repairment. There was no significant difference in the patency rate
among three different surgical treatments.
PMID- 28427125
TI - [The clinical value of SUDOSCAN in diagnosis of diabetic distal symmetrical
peripheral neuropathy].
AB - Objective: To evaluate the clinical value of SUDOSCAN in diagnosis of diabetic
distal symmetrical peripheral neuropathy. Methods: According to the diagnostic
criteria for multiple diabetic distal symmetrical peripheral neuropathy, a total
of 130 patients with type 2 diabetes mellitus (T2DM) in Department of
Endocrinology, the Affiliated Hospital of Qingdao University between August 2015
and July 2016 were divided into two groups, diabetic peripheral neuropathy group
(DPN group, 50 cases) and non-diabetic peripheral neuropathy group (NDPN group,
80 cases). Additional 80 healthy volunteers were selected as healthy control
group (NC group). SUDOSCAN was employed to detect electrochemical skin
conductance (ESC, the unit was MUS) of subjects' hands and feet, and the
correlation between sensory nerve conduction velocity (SCV) and ESC was analyzed
as well. Results: The average hands ESC in NC and T2DM group were (79.1+/-10.4)
MUS and (59.7+/-18.1) MUS, respectively; the average feet ESC were (82.0+/-8.2)
MUS and (62.1+/-21.8) MUS, respectively (both P<0.01). The average hands ESC in
DPN and NDPN group were (53.2+/-18.9) MUS and (63.7+/-16.5) MUS; the average feet
ESC were (53.5+/-24.4) MUS and (67.4+/-18.2) MUS, respectively (both P<0.05). The
hands and feet ESC were positively correlated with SCV, and the correlation
coefficient were 0.425 and 0.445, respectively (both P<0.01). The area under the
receiver operating characteristic curve (ROC) of hands and feet ESC to evaluate
diabetic symmetrical peripheral polyneuropathy were 0.785 and 0.768 (both
P<0.01). Conclusion: SUDOSCAN is a promising tool for the diagnosis of diabetic
symmetrical peripheral polyneuropathy.
PMID- 28427127
TI - [Surgical management of ophthalmic artery aneurysms via minimally invasive
frontolateral approach].
AB - Objective: To explore the minimally invasive techniques and outcome of carotid
ophthalmic artery aneurysms clipping via a frontolateral approach. Methods: The
clinical data of 95 patients with carotid ophthalmic artery aneurysms treated via
frontolateral approach in the last 1.5 years in Beijing Tiantan Hospital and
Beijing Anzhen Hospital were analyzed retrospectively.Before the operation,
digital subtraction angiogram (DSA) was performed among all patients.The patients
were divided into two groups by the lateral approach.According to preoperative
classification, surgical characteristics and prognosis were summarized. Results:
Ninety-five cases of ophthalmic aneurysms were divided into type I of 44 cases
(46.3%), type II of 34 cases (35.7%) and type III of 17cases (17.9%), according
to the results of DSA.The diameter of aneurysm was <10 mm (35 cases), 10-25 mm
(34 cases), and >25 mm (26 cases). In the 17 cases of subarachnoid hemorrhage
(SAH), 8 cases were ruptured carotid-ophthalmic artery aneurysms.Among those 95
patients, 93 were clipped successfully, 2 was trapped.Multiple aneurysms in 5
cases were treated in one surgical session through the same approach.No aneurysm
residual was found after postoperative CTA review.Ipsilateral vision of 3 cases
were decline.Cerebral infarction was appeared in 9 cases.All the others had a
good recovery. Conclusions: The carotid-ophthalmic artery aneurysms could be well
exposed. Microsurgery through frontolateral approach has the advantages such as
minimal invasion, less effect on the patients' look and simple procedure.The
frontolateral approach is safe and effective in surgery for ophthalmic segment of
the internal carotid artery aneurysms.
PMID- 28427128
TI - [The application value of contrast-enhanced ultrasound in the surgery of renal
masses].
AB - Objective: To investigate the clinical value of contrast-enhanced ultrasound in
the diagnosis of renal masses. Methods: A total of 50 patients with renal masses
who underwent partial nephrectomy were analyzed from January 2014 to October 2016
in the Department of Urology of China-Japan Union Hospital of Jilin University.In
the intraoperative contrast-enhanced ultrasound, the characteristics of
ultrasound imaging were recorded including location, size, boundary, echo, real
time internal and peripheral blood and renal pelvis distance, artery, guidance on
the selection of surgical methods, intraoperative real-time estimation of the
extent of tumor resection. Results: In the 50 patients, there were 49 cases
enhancement in the imaging of the cystic masses, 1 case had no
enhancement.Contrast-enhanced ultrasound assisted clinical accurate positioning
34 masses which were in the renal contour and not convex.And 15 patients were
found main arteries of renal occupied lesions.There were 38 cases whose distance
from occupying to pelvis was more than 0.5 cm, and maintained the original
operation scheme for partial nephrectomy.There were 12 cases whose distance from
occupying to pelvis was less than 0.5 cm, and proceeded radical resection.
Conclusions: Intraoperative contrast-enhanced ultrasound can provide a more
accurate imaging basis for the surgeon in partial nephrectomy.It's of great
significance for the correct choice of surgical procedures, and can reduce or
avoid the occurrence of postoperative complications.
PMID- 28427129
TI - [The role of FOXO3a-Bim signaling in triptolide induced bladder cancer T24 cells
apoptosis].
AB - Objective: To investigate the role of FOXO3a-Bim signaling in triptolide induced
bladder cancer T24 cells apoptosis. Methods: T24 cells were used and divided into
control group, triptolide group(50 nmol/L), MK2206 group(50 nmol/L triptolide+ 5
MUmol/L MK2206), FOXO3a-siRNA group(50 nmol/L triptolide+ 100 nmol/L FOXO3a
siRNA), Bim-siRNA group (50 nmol/L triptolide+ 100 nmol/L Bim-siRNA). MTT assay
was used to analyze the cells growth inhibition.Annexin V/PI staining was
implemented to detect cell apoptosis rate, the expression of p-Akt, Akt, p
FOXO3a, FOXO3a, Bim, Bax.Cleaved-caspase 3 was analyzed by Western blot. Results:
After treatment with triptolide 25, 50, 100, 250 nmol/L, the cell growth
inhibition rates at 24 hours(17%+/-9%, 24%+/-5%, 43%+/-8%, 61%+/-8%), 48 hours
(20%+/-7%, 34%+/-6%, 56%+/-7%, 74%+/-5%) and 72 hours(32%+/-8%, 41%+/-7%, 69%+/
7%, 84%+/-3%) were significantly higher than control group respectively.The
IC(50) at 24, 48, 72 hours were (113+/-10), (91+/-8), (68+/-5) nmol/L; the cell
apoptosis rates at 24 hours (10%+/-4%, 15%+/-5%, 29%+/-8%, 46%+/-8%), 48 hours
(16%+/-5%, 24%+/-6%, 40%+/-7%, 55%+/-9%) and 72 hours (27%+/-4%, 38%+/-5%, 50%+/
9%, 65%+/-8%) were significantly increased (P<0.05). Western blot showed that
triptolide reduced the expression of p-Akt, p-FOXO3a and increased the expression
of Bim, Bax, cleaved-caspase 3.The cell inhibition rate in Triptolide group
(30%+/-8%) was significantly higher than that in the control group (P<0.05) and
the rates in MK2206 group (54% +/-6%), FOXO3a-siRNA group (18%+/-7%) and Bim
siRNA group (11%+/-6%) were also higher than the control group.Compared with the
triptolide group, the inhibition rate in MK2206 group was significantly
increased, but decreased in FOXO3a-siRNA group and Bim-siRNA group(P<0.05).
Conclusion: Triptolide induces T24 cells apoptosis through FOXO3a-Bim signaling
pathway.
PMID- 28427130
TI - [To see the future development of burn medicine from the view of holistic
integrative medicine].
AB - The therapeutic methods and effects have been improved greatly in the past few
decades for burn care and management with several important advancements which
have resulted in more effective patient stabilization and significantly decreased
mortality in China. However, the challenges still exist, such as how to further
improve the recovery of the patients' appearance and function, and how to advance
the treatment of severe deep extensive burn injury, etc. The theory of holistic
integrative medicine (HIM) provides a new opportunity for the development of
clinical medicine. This article emphasizes the important roles of HIM in
exploration of burn medicine, considering the advanced development of modern life
sciences and relevant techniques.
PMID- 28427131
TI - [Recognizing prevention and treatment of burn sepsis with the concept of holistic
integrative medicine].
AB - Sepsis remains a major cause of death in severe burns. The effect of sepsis
management is influenced by its complicated pathophysiologic changes. In order to
improve the outcome of burn sepsis, the predisposing factor of sepsis after burn
analyzed by advanced technology, the early prevention, antibiotics therapy, and
combined treatment in severe burns with sepsis are discussed using the concept of
holistic integrative medicine.
PMID- 28427132
TI - [Influences of abaR gene on biofilm formation of Acinetobacter baumannii].
AB - Objective: To detect drug-resistant phenotype and abaR gene of Acinetobacter
baumannii (AB) and investigate influences of abaR gene on biofilm formation of
AB. Methods: From February to July 2014, 159 strains AB were collected from
Department of Clinical Microbiology of Ruijin Hospital of School of Medicine of
Shanghai JiaoTong University and numbered starting from 1 according time when
they were collected. (1) The above-mentioned 159 strains of AB were identified by
detecting gene sequence of 16S ribosomal DNA. According to results of drug
sensitivity test, extensively drug-resistant strains and sensitive strains of AB
were selected and counted, and their sources were recorded. (2) Extensively drug
resistant strains and sensitive strains of AB were collected to measure biofilm
formation (denoted as absorbance value) by methyl thiazolyl tetrazolium method
when strains at culture hour 12, 24, 48 and 72. (3) The abaR gene sequence of
ATCC 17978 of AB was analyzed through Gene banks of National Center for
Biotechnology Information and compared with AqsR gene sequence of LuxR type
receptor of Acinetobacter oleivorans DR1. No. 87 and No. 96 AB strains were
amplified and sequenced by polymerase chain reaction according to target gene
sequence of abaR of ATCC 17978 of AB. The sequencing result was compared with
abaR gene sequence of ATCC 17978. (4) No. 87 and No. 96 AB strains were collected
and divided into 0.1% dimethyl sulfoxide (DMSO) group, 10 MUmol/L N-heptanoyl-L
Homoserine lactone (C7-HSL) group, 10 MUmol/L N-(3-Hydroxydodecanoyl)-DL
homoserine lactone (OH-dDHL) group, 1% DMSO group, 100 MUmol/L C7-HSL group, and
100 MUmol/L OH-dDHL, with 3 wells of each group. AB strains in the above groups
were respectively dealt with DMSO of corresponding final volume fraction, C7-HSL
and OH-dDHL of corresponding final amount-of-substance concentration. Biofilm
formation (denoted as absorbance value) of AB was measured by methyl thiazolyl
tetrazolium method at culture hour 12, 24, 48 and 72. Data were processed with
analysis of variance of factorial design, one-way analysis of variance, LSD test
and Bonferroni correction. Results: (1) There were 18 extensively drug-resistant
strains and 5 sensitive strains of AB. Samples of extensively drug-resistant
strains were mainly collected from Emergency ICU and Department of Burns and
Plastic Surgery of our hospital and were mainly from sputum, blood, and wound
exudate. Samples of sensitive strains were collected dispersedly and were mainly
from sputum. (2) Absorbance values of extensively drug-resistant strains and
sensitive strains of AB at all culture time points were similar (with P values
above 0.05). Absorbance value of extensively drug-resistant strains of AB at
culture hour 24 was obviously higher than that of these strains at culture hour
12, 48, or 72 (with P values below 0.01). Absorbance value of sensitive strains
of AB at culture hour 24 was obviously higher than that of these strains at
culture hour 12 (P<0.01). (3) AbaR gene sequence of LuxR type receptor existed in
AB. Similarity ratio between abaR gene sequence and LuxR type receptor AqsR gene
sequence in Acinetobacter oleivorans DR1 was 87%. Similarity ratios between abaR
gene sequence of No. 87 and No. 96 strains and ATCC 17978 of AB were 98% and 99%,
respectively. (4) Absorbance values of 0.1% DMSO group of No. 87 strain at all
culture time points were similar to those of 1% DMSO group (with P values above
0.05). Absorbance value of 0.1% DMSO group of No. 96 strain at culture hour 12
was obviously lower than that of 1% DMSO group (P<0.01), while that at culture
hour 24 was obviously lower than that of 1% DMSO group (P<0.01). Absorbance
values of 10 MUmol/L C7-HSL group of No. 87 and No. 96 strains at culture hour 24
were obviously lower than those of 0.1% DMSO group (with P values below 0.01).
Absorbance values of 100 MUmol/L C7-HSL group of No. 87 strain at all culture
time points were similar to those of 1% DMSO group, respectively (with P values
above 0.05). Absorbance value of 100 MUmol/L C7-HSL group of No. 96 strain at
culture hour 12 was lower than that of 1% DMSO group (P<0.01). Absorbance values
of 10 MUmol/L OH-dDHL group of No. 87 and No. 96 strains were similar to those of
0.1% DMSO group (with P values above 0.05). Absorbance values of 100 MUmol/L OH
dDHL group of No. 87 strain at all culture time points were similar to those of
1% DMSO group (with P values above 0.05). Absorbance value of 100 MUmol/L OH-dDHL
group of No. 96 strain at culture hour 12 was obviously higher than that of 1%
DMSO group (P<0.01). Absorbance values of 0.1% DMSO group and 1% DMSO group of
No. 87 and No. 96 strains at culture hour 24 were obviously higher than those at
culture hour 12 and 48 (with P values below 0.01). Conclusions: Extensively drug
resistant strains of AB exist commonly. AbaR gene exists in AB has relation with
biofilm formation of AB.
PMID- 28427133
TI - [Effects of application of vancomycin in the early stage of patients with
extremely severe burn].
AB - Objective: To evaluate the effects of application of vancomycin in the early
stage of patients with extremely severe burn, in order to provide reference to
drug for anti-infection treatment in the early stage of patients with extremely
severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd,
2014, admitted to the Department of Intensive Care in our hospital were
retrospectively analyzed. The clinical efficacy of continuously intravenous
dripping of vancomycin (combined with imipenem) in the early stage of burns
(before and on post burn day 14) was analyzed. (1) The steady state plasma
concentration of vancomycin was monitored respectively 30 min before the third,
sixth, and tenth medication with direct chemiluminescent imaging method. (2) The
distribution of Gram-positive bacteria of patients during hospitalization and
their drug resistance to 14 antibiotics commonly used in clinic were analyzed.
(3) Serum level of procalcitonin (PCT), white blood cell count, percentage of
neutrophils before and after treatment, and efficacy grade of anti-infection
treatment in the early stage of burns were analyzed. (4) Serum levels of
aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before
and after treatment, and the adverse effects during medication were analyzed. The
WHONET 5.5 statistical software was used to analyze the distribution of Gram
positive bacteria in all the pathogens, and the status of drug resistance of Gram
positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum
test. Results: (1) Twenty-nine times of steady state plasma concentration
monitoring were performed in the patients in total, with the steady state plasma
concentration of vancomycin from 4.3 to 42.1 MUg/mL. In the monitoring before
third, sixth, and tenth medication, the percentages of result reaching the
standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive
bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9
(11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of
Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2
(2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus
strains were with high drug resistance to antibiotics including penicillins,
erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin,
and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug
resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and
low drug resistance to linezolid and teicoplanin. The above-mentioned
Staphylococcus strains were all sensitive to vancomycin. Two strains of
vancomycin-resistant Enterococcus were detected in the above-mentioned
Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage
of neutrophils of patients were (8.1+/-7.5) ng/mL, (24+/-10)*10(9)/L, and 0.898+/
0.029 before treatment, which were significantly higher than (3.0+/-2.8) ng/mL,
(12+/-5)*10(9)/L, and 0.867+/-0.016 after treatment (with Z values respectively
2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment,
excellence, progess, and invalid results were achieved in 7, 5, and 3 patients,
with the effective percentage of 4/5 in clinic. (4) There were no statistically
significant differences in serum levels of AST, ALT, and creatinine of patients
between before and after treatment (with Z values respectively-0.057, -1.508, and
-1.363, P values above 0.05). Only one patient had liver and renal dysfunction
during treatment. Conclusions: The positive and reasonable use of vancomycin can
remove most of the Gram-positive bacteria, and control the development of sepsis
combined with imipenem in the early stage of patients with extremely severe burn.
However, the dose of vancomycin should be individualized and the steady state
plasma concentration should be monitored to maintain the blood concentration
within the safe and effective range, so as to improve the rational use of
vancomycin.
PMID- 28427134
TI - [Role of bone marrow tyrosine kinase on chromosome X in the production of pro
inflammatory cytokines from mouse mononuclear-macrophages RAW264.7 induced by
endotoxin/lipopolysaccharide and its mechanism].
AB - Objective: To investigate the role of bone marrow tyrosine kinase on chromosome X
(BMX) in the production of tumor necrosis factor alpha (TNF-alpha) and
interleukin-1beta (IL-1beta) from mouse mononuclear-macrophages induced by
endotoxin/lipopolysaccharide (LPS) and its related mechanism. Methods: Mouse
mononuclear-macrophages RAW264.7 were inoculated in 6-well plates and routinely
cultured for the following experiments. (1) Cells were collected and divided into
blank control group, LPS control group, and 75, 750, 7 500, 75 000 nmol/L BMX-IN
1 pretreatment groups according to the random number table, with 8 wells in each
group. Cells in blank control group were routinely cultured for 25 h. Cells in
LPS control group were routinely cultured for 24 h and stimulated by LPS in the
final mass concentration (the same below) of 0.1 MUg/mL for 1 h. Cells in the
latter 4 groups were pretreated with BMX-IN-1 in the final molarity (the same
below) of 75, 750, 7 500, 75 000 nmol/L for 24 h and stimulated by 0.1 MUg/mL LPS
for 1 h. The mRNA expression of TNF-alpha of cells in each group was determined
by real-time fluorescent quantitative reverse transcription polymerase chain
reaction (RT-PCR) to screen the optimum concentration of BMX-IN-1. (2) Cells were
collected and divided into LPS control group and 2, 4, 8, 12, 18 h BMX-IN-1
pretreatment groups according to the random number table, with 8 wells in each
group. Cells in LPS control group were stimulated by 0.1 MUg/mL LPS for 1 h.
Cells in the latter 5 groups were pretreated with optimum concentration of BMX-IN
1 for 2, 4, 8, 12, 18 h respectively and stimulated by 0.1 MUg/mL LPS for 1 h.
The mRNA expression of TNF-alpha of cells in each group was determined by real
time fluorescent quantitative RT-PCR to screen the optimum time for BMX-IN-1 pre
treatment. (3) Cells were collected and divided into blank control group, BMX-IN
1 control group, LPS control group, and BMX-IN-1+ LPS group according to the
random number table, with 16 wells in each group. Cells in blank control group
were routinely cultured for the optimum time plus 1 h. Cells in BMX-IN-1 control
group were pretreated with BMX-IN-1 in the optimum concentration for the optimum
time and then routinely cultured for 1 h. Cells in LPS control group were
routinely cultured for the optimum time and then stimulated by 0.1 MUg/mL LPS for
1 h. Cells in BMX-IN-1+ LPS group were pretreated with BMX-IN-1 in the optimum
concentration for the optimum time and then stimulated by 0.1 MUg/mL LPS for 1 h.
The mRNA expressions of TNF-alpha and IL-1beta were determined by real-time
fluorescent quantitative RT-PCR, and the activity of BMX and p38 mitogen
activated protein kinase (MAPK) were determined by Western blotting, with 8
samples in each determination. Data were processed with one-way analysis of
variance and LSD test. Results: (1) Compared with that in blank control group,
the mRNA expression of TNF-alpha of cells was significantly increased in the
other 5 groups (with P values below 0.01). Compared with that in LPS control
group, the mRNA expression of TNF-alpha of cells was decreased in each BMX-IN-1
pretreatment group, but only the mRNA expression of TNF-alpha of cells in 75 000
nmol/L BMX-IN-1 pretreatment group was significantly decreased (P<0.05). The
optimum concentration of BMX-IN-1 was 75 000 nmol/L. (2) Compared with that in
LPS control group, the mRNA expression of TNF-alpha of cells was not
significantly changed in 2 and 4 h BMX-IN-1 pretreatment groups (with P values
above 0.05) but significantly decreased in 8, 12, and 18 h BMX-IN-1 pretreatment
groups (P<0.05 or P<0.01). The mRNA expression of TNF-alpha of cells in 12 h BMX
IN-1 pretreatment group was the lowest. The optimum time for BMX-IN-1 pre
treatment was 12 h. (3) The mRNA expressions of TNF-alpha and IL-1beta of cells
in BMX-IN-1 control group were 0.97+/-0.13 and 0.98+/-0.06, respectively, which
were similar to 1.00 of blank control group (with P values above 0.05). The mRNA
expressions of TNF-alpha and IL-1beta of cells in LPS control group were 2.97+/
0.17 and 3.07+/-0.60, respectively, while those in BMX-IN-1+ LPS group were
2.31+/-0.94 and 2.55+/-0.73, respectively, with the 4 values significantly higher
than those in blank control group (with P values below 0.01). The mRNA
expressions of TNF-alpha and IL-1beta of cells in BMX-IN-1+ LPS group were
significantly lower than those in LPS control group (with P values below 0.05).
The activity values of BMX and p38MAPK of cells in BMX-IN-1 control group were
0.95+/-0.19 and 0.98+/-0.18, respectively, which were close to 1.00+/-0.14 and
1.00+/-0.22 of blank control group (with P values above 0.05). The activity
values of BMX and p38MAPK of cells in LPS control group were 1.98+/-0.33 and
2.05+/-0.34, respectively, which were significantly higher than those of blank
control group (with P values below 0.01). The activity values of BMX and p38MAPK
of cells in BMX-IN-1+ LPS group were 1.00+/-0.17 and 1.67+/-0.27, respectively,
which were obviously lower than those of LPS control group (P<0.05 or P<0.01).
Conclusions: BMX can increase the production of pro-inflammatory cytokines TNF
alpha and IL-1beta from mouse mononuclear-macrophages induced by LPS, which may
be associated with the activation of the p38MAPK pathway by BMX.
PMID- 28427135
TI - [Effects of allogeneic bone marrow mesenchymal stem cells on polarization of
peritoneal macrophages in rats with sepsis].
AB - Objective: To explore the effects of allogeneic bone marrow mesenchymal stem
cells (BMSCs) on polarization of peritoneal macrophages isolated from rats with
sepsis induced by endotoxin/lipopolysaccharide (LPS). Methods: (1) BMSCs were
isolated, cultured and purified from 5 SD rats with whole bone marrow adherent
method. The third passage of cells were collected for morphologic observation,
detection of expressions of stem cell surface markers CD29, CD44, CD45, and CD90
with flow cytometer, and identification of osteogenic and adipogenic
differentiation. (2) Another 45 SD rats were divided into sham injury group (SI,
n=5), LPS control group (LC, n=20), and BMSCs-treated group (BT, n=20) according
to the random number table. Rats in groups LC and BT were injected with LPS (5
mg/kg) via tail vein to induce sepsis; rats in group SI were injected with the
same amount of normal saline to simulate the damage. At post injury hour (PIH) 1,
rats in group BT were given 1 mL BMSCs (2*10(6)/mL) via tail vein injection; rats
in another two groups were injected with equal volume of phosphate buffer saline.
Five rats in group SI at PIH 24 and in groups LC and BT at PIH 6, 12, 24, and 48
were sacrificed to harvest lung tissue for pathological observation with HE
staining. In addition, rats in group SI at PIH 24 and in groups LC and BT at PIH
24 and 48 were simultaneously performed with intraperitoneal injection of low
glucose DMEM. Then peritoneal fluid was harvested to culture peritoneal
macrophages. Flow cytometer was used to assess the positive expression of cell
makers of macrophages including CD68 (making gate), CD11c, and CD206 in group SI
at PIH 24 and in groups LC and BT at PIH 24 and 48. Data were processed with one
way analysis of variance and LSD test. Results: (1) The third passage of cells
showed uniform fiber-like shape similar to fibroblasts. These cells showed
positive expressions of CD29, CD44, CD90 and weak positive expression of CD45.
They were able to differentiate into osteoblasts and adipocytes. These cells were
identified as BMSCs. (2) At PIH 24, the structure of pulmonary alveoli of rats in
group SI was clear and complete with no congestion or inflammatory cell
infiltration. At PIH 6, the structure of pulmonary alveoli of rats in groups LC
and BT was clear with a small amount of inflammatory cell infiltration, slight
congestion and pulmonary interstitial thickening. At PIH 12, the inflammatory
responses in lung tissue of rats in group LC were more severe than those in group
BT with a large amount of inflammatory cell infiltration, serious congestion, and
obvious pulmonary interstitial thickening. The pathological results of rats in
group BT at PIH 12 was consistent with the results at PIH 6. At PIH 24, the
pathological results of rats in groups LC and BT were similar to the results at
PIH 12. At PIH 48, the structure of pulmonary alveoli tissue of rats in group LC
was still severely disrupted, with a large number of inflammatory cell
infiltration and congestion in lung tissue, but pulmonary interstitial thickening
was slightly alleviated than before. The condition of rats in group BT nearly
recovered to that in group SI. (3) At PIH 24, the positive expression rate of
CD11c in peritoneal macrophages of rats in group LC [(83+/-10)%] was close to
that in group BT [(87+/-7)%, P>0.05], and they were both significantly higher
than the rate in group SI [(55+/-12)%, with P values below 0.01]. The positive
expression rate of CD11c in peritoneal macrophages of rats in group LC [(59+/
11)%] at PIH 48 was close to that in group SI at PIH 24 (P>0.05), and they were
both significantly higher than the rate in group BT [(20+/-11)%] at PIH 48 (with
P values below 0.01). At PIH 24, the positive expression percentages of CD206 in
peritoneal macrophages of rats were similar among the three groups (with P values
above 0.05). The positive expression percentage of CD206 in peritoneal
macrophages of rats in group SI at PIH 24 was close to that in group BT at PIH 48
(P>0.05), and they were both significantly lower than the percentage in group LC
at PIH 48 (with P values below 0.01). Conclusions: BMSCs can reduce the
pathological inflammatory responses in the lung of rats with sepsis and inhibit
peritoneal macrophages from polarizing into M1 phenotype, whereas they can not
promote macrophages to polarize into M2 phenotype.
PMID- 28427136
TI - [Effects and related mechanism of bivalirudin on the survival of random skin flap
on the back of rat].
AB - Objective: To investigate the effects and related mechanism of bivalirudin on the
survival of random skin flap on the back of rat. Methods: Thirty SD rats were
divided into bivalirudin group and normal saline group according to the random
number table, with 15 rats in each group. The random flap model with size of 9
cm*3 cm was reproduced on the back of rats in two groups. Immediately post
injury, rats in bivalirudin group were intraperitoneally injected with 5 mg/mL
bivalirudin (0.8 mL/kg), while rats in normal saline group were intraperitoneally
injected with normal saline (0.8 mL/kg) once a day. The continuous injection
lasted for 7 days. The flap was divided into distal area, middle area and
proximal area averagely based on the flap blood supply. On post injury day (PID)
1, 3, and 7, the overall survival of each area of flap was observed with naked
eyes. On PID 7, the survival rate of flap was calculated, and then the morphology
of skin tissue at the center of the three areas of flap was observed by HE
staining, the microvessel density (MVD) of the middle area of flap was
calculated, and the expression of vascular endothelial growth factor (VEGF) of
the middle area of flap was detected with immunohistochemical staining. Data were
processed with t test. Results: (1) On PID 1, flaps of rats in two groups had
different degrees of swelling, mainly concentrated in distal area, but there was
no obvious necrosis. The middle area and proximal area of flaps in two groups
were survived. On PID 3, the necrosis of flaps of rats in two groups was
concentrated in the middle area, while the proximal area of flap was still in
survival state, and most distal area of flap was necrosis with a little scab. On
PID 7, the necrosis of middle area of flaps of rats in two groups was gradually
fused, and the survival area of flap of rats in bivalirudin group was larger than
that in normal saline group. The distal area of flap was almost necrotic, and the
proximal area of flap was almost survived. (2) On PID 7, the survival rate of
flap of rats in bivalirudin group was (64+/-4)%, significantly higher than that
in normal saline group [(45+/-3)%, t=13.49, P<0.01]. (3) On PID 7, the
histological morphology of distal area of flap of rats in two groups was similar,
the inflammatory cells were infiltrated abundantly, and tissue edema was obvious.
A large number of new blood vessels appeared in the middle area of flap of rats
in bivalirudin group, with the formation of collateral vessels, and basic
dilation of new blood vessels was seen. There were fewer new blood vessels
appeared in the middle area of flap of rats in normal saline group, and dilation
of new blood vessels was not obvious. There was little inflammatory cells
infiltration in the proximal area of flap of rats in two groups. Compared with
that in normal saline group, tissue edema extent of proximal area of flap of rats
in bivalirudin group was less, and expansion was observed in more blood vessels.
(4) The MVD of middle area of flap of rats in bivalirudin group was (26+/
5)/mm(2,) significantly higher than that in normal saline group [(18+/-3)/mm(2,)
t=5.43, P<0.05]. (5) The expression of VEGF of middle area of flap of rats in
bivalirudin group was 6 534+/-384, significantly higher than that in normal
saline group (4 659+/-448, t=12.31, P<0.05). Conclusions: Bivalirudin can promote
the survival of random skin flap in rats, and the mechanisms may include reducing
the formation of thrombosis, improving the blood supply of flap, and increasing
the expression of VEGF, promoting the formation of new blood vessels.
PMID- 28427137
TI - [Bibliometric analysis of scientific articles on epidemiological study of burns
in China].
AB - Objective: To analyze the current status of epidemiological study of burns in
China, and to explore the related strategies. Methods: Retrospective or cross
sectional scientific articles in Chinese or English on epidemiological study of
burns in China published from January 2005 to December 2015 were systemically
retrieved from 4 databases. The databases include PubMed, Embase, China Biology
Medicine disc, and Chinese Journals Full-text Database. From the results
retrieved, data with regard to publication year, journal distribution, number of
institutions participated in the study, affiliation of the first author and its
location, and admission time span and age of patients in all the scientific
articles were collected. Furthermore, the definition of age range and the
grouping method of age of pediatric patients in English articles on
epidemiological study of pediatric burns of China were recorded. Data were
processed with descriptive statistical analysis. Results: A total of 256
scientific articles conforming to the study criteria were retrieved, among which
214 (83.59%) articles were in Chinese, and 42 (16.41%) articles were in English;
242 (94.53%) articles were retrospective studies, and 14 (5.47%) articles were
cross-sectional studies. During the 11 years, the number of the relevant articles
was fluctuant on the whole. The scientific articles were published in 130
journals, with 42 English articles in source journals for SCIENCE CITATION INDEX
EXPANDED-JOURNAL LIST, accounting for 16.41%, and 116 Chinese articles in Source
Journal for Chinese Scientific and Technical Papers, accounting for 45.31%.
Totally 215 (83.98%) articles were single-center studies, and 29 (11.33%)
articles were multicenter studies which were conducted by three or more centers.
The number of affiliations of the first author of articles was 161 in total. The
top 10 institutions regarding the article publishing number published 58
articles, accounting for 22.66%. Scientific articles on epidemiological study of
burns were retrieved with location of affiliation of the first author in 31
provinces, autonomous regions, and municipalities directly under the Central
Government in Mainland China, and also in Taiwan Province and Hong Kong Special
Administrative Region, among which Shanghai ranked first with 24 (9.38%) articles
published. The admission time span of patients in the articles ranged from 3
months to 47 years, with 120 (46.87%) articles from 3 months to 5 years, 79
(30.86%) articles from 6 to 10 years, and 57 (22.27%) articles more than 10
years, respectively. Regarding the age of patients in the study, 123 articles
were on epidemiological study of pediatric burns, and 16 articles on
epidemiological study of elderly burns, accounting for 48.05% and 6.25%,
respectively. Further analysis of articles on epidemiological study of pediatric
burns in English showed that there was no standard definition of age range or
unified grouping method of age for pediatric burn patients. Conclusions: The
epidemiological study of burns in China has been carried out nationwide, but the
number of institutions conducted relevant study is not that much, and multicenter
epidemiological studies remain scanty. The quality of the articles needs to be
further improved. The epidemiological study of elderly burns is relatively
deficient and calls for more attention. The epidemiological study of burns in
China lacks regularity or continuity in time scope. There is an urgent need for
the guideline on classification method for items of epidemiological study of
burns in China so as to standardize the related research.
PMID- 28427138
TI - [Advances in the research of treatment of burns in the elderly].
AB - With our country going into the aging society, burns in the elderly often occur.
Studies have shown that the number of elderly burn patients has reached 13% to
20% of the total number of burn patients. As the sensory and cognitive functions
are low, skin is thinning, the functions of heart, lung, and kidney are reduced,
the immunity is impaired, and other physiological characteristics exist in the
elderly, the wounds of elderly burn patients often heal slowly, and the mortality
is high. At present, there is still a lack of enough attention to the elderly
burn patients. In this review, according to the physiological characteristics of
the elderly, for reference to our peers, we make a summary of the treatment of
elderly burn patients, such as fluid resuscitation, wound treatment, acute kidney
injury management, infection management, and nutritional support.
PMID- 28427139
TI - [Advances in the research of mechanism in prevention and treatment of scar with
botulinum toxin type A and its clinical application].
AB - Scar is a common complication in wound healing process, and how to effectively
prevent and treat it is a hot and difficult problem in burns and plastic surgery
field. Botulinum toxin type A is a neurotoxin that has been widely and
effectively used in the cosmetic surgery field such as anti-wrinkle and thin
face. In recent years, botulinum toxin type A has been applied in prevention and
treatment of scar, which causes a great concern. Nowadays, the relevant reports
have gradually increased, and the mechanisms have been explored more deeply. This
article aims to summarize the possible mechanisms and clinical reports on the
prevention and treatment of scar by botulinum toxin type A to provide a new way
for the prevention and treatment of scar after surgery.
PMID- 28427142
TI - iRNA-PseU: Identifying RNA pseudouridine sites.
AB - As the most abundant RNA modification, pseudouridine plays important roles in
many biological processes. Occurring at the uridine site and catalyzed by
pseudouridine synthase, the modification has been observed in nearly all kinds of
RNA, including transfer RNA, messenger RNA, small nuclear or nucleolar RNA, and
ribosomal RNA. Accordingly, its importance to basic research and drug development
is self-evident. Despite some experimental technologies have been developed to
detect the pseudouridine sites, they are both time-consuming and expensive.
Facing the explosive growth of RNA sequences in the postgenomic age, we are
challenged to address the problem by computational approaches: For an
uncharacterized RNA sequence, can we predict which of its uridine sites can be
modified as pseudouridine and which ones cannot? Here a predictor called "iRNA
PseU" was proposed by incorporating the chemical properties of nucleotides and
their occurrence frequency density distributions into the general form of pseudo
nucleotide composition (PseKNC). It has been demonstrated via the rigorous
jackknife test, independent dataset test, and practical genome-wide analysis that
the proposed predictor remarkably outperforms its counterpart. For the
convenience of most experimental scientists, the web-server for iRNA-PseU was
established at http://lin.uestc.edu.cn/server/iRNA-PseU, by which users can
easily get their desired results without the need to go through the mathematical
details.
PMID- 28427143
TI - Activity-induced spontaneous spikes in GABAergic neurons suppress seizure
discharges: an implication of computational modeling.
AB - BACKGROUND: Epilepsy, a prevalent neurological disorder, appears self
termination. The endogenous mechanism for seizure self-termination remains to be
addressed in order to develop new strategies for epilepsy treatment. We aim to
examine the role of activity-induced spontaneous spikes at GABAergic neurons as
an endogenous mechanism in the seizure self-termination. METHODS AND RESULTS:
Neuronal spikes were induced by depolarization pulses at cortical GABAergic
neurons from temporal lobe epilepsy patients and mice, in which some of these
neurons fired activity-induced spontaneous spikes. Neural networks including
excitatory and inhibitory neurons were computationally constructed, and their
functional properties were based on our studies from whole-cell recordings. With
the changes in the portion and excitability of inhibitory neurons that generated
activity-induced spontaneous spike, the efficacies to suppress synchronous
seizure activity were analyzed, such as its onset time, decay slope and spike
frequency. The increases in the proportion and excitability of inhibitory neurons
that generated activity-induced spontaneous spikes effectively suppressed seizure
activity in neural networks. These factors synergistically strengthened the
efficacy of seizure activity suppression. CONCLUSION: Our study supports a notion
that activity-induced spontaneous spikes in GABAergic neurons may be an
endogenous mechanism for seizure self-termination. A potential therapeutic
strategy for epilepsy is to upregulate the cortical inhibitory neurons that
generate activity-induced spontaneous spikes.
PMID- 28427144
TI - Human papillomavirus infection as a prognostic marker for lung adenocarcinoma: a
systematic review and meta-analysis.
AB - Although a number of studies have investigated the association between human
papillomavirus (HPV) and lung cancer prognosis, the results remain inconsistent.
We therefore conducted a meta-analysis of epidemiologic studies to address this
issue. Searches of the MEDLINE and EMBASE electronic databases from their
inception until June 30, 2016 yielded nine studies involving a total of 1,205
lung cancer cases that were used to conduct the meta-analysis. Study-specific
risk estimates were pooled using a random-effects model. The pooled hazard ratio
(HR) comparing HPV-positive to HPV-negative cancers 1.00 (95% confidence interval
(CI): 0.78-1.28) was not significantly correlated with overall survival. However,
lung adenocarcinoma patients with HPV infections exhibited a survival benefit
compared to those without HPV infection (HR=0.69, 95% CI: 0.50-0.96). This meta
analysis suggests HPV infection is a prognostic marker in lung adenocarcinoma. To
further elucidate the epidemiology and pathogenesis of HPV infections in lung
cancer, future large prospective studies are encouraged to stratify survival
analysis based on the pathological type and clinical stage of the cancer.
PMID- 28427145
TI - Uncoupling genotoxic stress responses from circadian control increases
susceptibility to mammary carcinogenesis.
AB - We previously demonstrated that chemopreventive methylselenocysteine (MSC)
prevents N-Nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in the
susceptible Fischer 344 (F344) rats by enhancing NAD+-dependent SIRT1 activity,
restoring circadian expression of Period 2 (Per2) and circadian controlled genes.
Here, we show that compared to the genetically resistant Copenhagen (COP) rat
strain, mammary glands of the F344 rats have a 4-hour phase delay in circadian
expression of Per2. Consequently, F344 rats failed to increase SIRT1 activity and
circadian expression of Per2 and DDRR genes after exposure to NMU. Exposure of
COP rats to NMU had the opposite effect, enhancing SIRT1 activity, increasing
circadian expression of Per2 and DDRR genes. Significantly, SIRT1 activity and
circadian expression of Per2 and DDRR genes in NMU-treated F344 rats on a
chemopreventive regimen of MSC approximated those in NMU-treated COP rats. These
results indicated that COP rats have an increased capacity to maintain NAD+
dependent SIRT1 activity under genotoxic stress. This contention was supported by
increased stability of the period and phase of circadian locomotor activity in
COP vs F344 rats exposed to changing light conditions. The increased sensitivity
and rapid response of COP to changing light were correlated with the enhanced
circadian response of this strain to carcinogen. Disturbance of circadian rhythm
by jet lag also disrupted circadian expression of Per2 and DDRR genes, and
accelerated mammary tumorigenesis in rodent models. These results suggested that
uncoupling of DDRR responses from circadian control by environmental stresses and
endogenous factors increases susceptibility to mammary carcinogenesis, possibly
by inducing a promutagenic state.
PMID- 28427146
TI - microRNA-200c/141 upregulates SerpinB2 to promote breast cancer cell metastasis
and reduce patient survival.
AB - The microRNA-200 (miR-200) family is associated with tumor metastasis and poor
patient prognosis. We found that miR-200c/141 cluster overexpression upregulated
SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We
observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear
localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol
acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative
to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2,
were downregulated compared to controls. In mouse xenograft models, miR-200c/141
cluster overexpression promoted lymph node and lung metastasis, and siRNA
mediated SerpinB2 knockdown decreased lung metastasis, suggesting that SerpinB2
mediates miR-200c/141-induced lung metastasis. We also explored the clinical
significance of SerpinB2 protein status through analysis of primary breast tumor
samples and The Cancer Genome Atlas (TCGA) data. High SerpinB2 levels were
associated with reduced survival and increased lymph node metastasis in breast
cancer patients. SerpinB2 was overexpressed in the TN breast cancer subtype as
compared to the luminal subtype. The present study demonstrates that SerpinB2
promotes miR-200c/141 cluster overexpression-induced breast cancer cell
metastasis, and SerpinB2 overexpression correlates with increased metastatic
potential and unfavorable outcomes in breast cancer patients. SerpinB2 may be a
useful biomarker for assessing metastasis risk in breast cancer patients.
PMID- 28427147
TI - BRCA1 controls the cell division axis and governs ploidy and phenotype in human
mammary cells.
AB - BRCA1 deficiency may perturb the differentiation hierarchy present in the normal
mammary gland and is associated with the genesis of breast cancers that are
genomically unstable and typically display a basal-like transcriptome. Oriented
cell division is a mechanism known to regulate cell fates and to restrict tumor
formation. We now show that the cell division axis is altered following shRNA
mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated
normal human mammary cells with graded consequences in progeny cells that include
aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective
loss of cells with luminal features. BRCA1 depletion stabilizes HMMR abundance
and disrupts cortical asymmetry of NUMA-dynein complexes in dividing cells such
that polarity cues provided by cell-matrix adhesions were not able to orient
division. We also show that immortalized mammary cells carrying a mutant BRCA1
allele (BRCA1 185delAG/+) reproduce many of these effects but in this model,
oriented divisions were maintained through cues provided by CDH1+ cell-cell
junctions. These findings reveal a previously unknown effect of BRCA1 suppression
on mechanisms that regulate the cell division axis in proliferating, non
transformed human mammary epithelial cells and consequent downstream effects on
the mitotic integrity and phenotype control of their progeny.
PMID- 28427148
TI - In-depth proteomic profiling of left ventricular tissues in human end-stage
dilated cardiomyopathy.
AB - Dilated cardiomyopathy (DCM) is caused by reduced left ventricular (LV)
myocardial function, which is one of the most common causes of heart failure
(HF). We performed iTRAQ-coupled 2D-LC-MS/MS to profile the cardiac proteome of
LV tissues from healthy controls and patients with end-stage DCM. We identified
4263 proteins, of which 125 were differentially expressed in DCM tissues compared
to LV controls. The majority of these were membrane proteins related to cellular
junctions and neuronal metabolism. In addition, these proteins were involved in
membrane organization, mitochondrial organization, translation, protein
transport, and cell death process. Four key proteins involved in the cell death
process were also detected by western blotting, indicated that cell death was
activated in DCM tissues. Furthermore, S100A1 and eEF2 were enriched in the
"cellular assembly and organization" and "cell cycle" networks, respectively. We
verified decreases in these two proteins in end-stage DCM LV samples through
multiple reaction monitoring (MRM). These observations demonstrate that our
understanding of the mechanisms underlying DCM can be deepened through comparison
of the proteomes of normal LV tissues with that from end-stage DCM in humans.
PMID- 28427149
TI - Interaction between PPAR gamma and SORL1 gene with Late-Onset Alzheimer's disease
in Chinese Han Population.
AB - AIMS: To investigate the impact of sortilin-related receptor 1 gene 1 (SORL1) and
peroxisome proliferator activated receptor gamma (PPAR G) gene single nucleotide
polymorphisms (SNPs), gene- gene and gene- environment interactions and haplotype
on late-onset Alzheimer's disease (LOAD) risk. METHODS: Hardy-Weinberg
equilibrium (HWE), haplotype analysis and pairwise linkage disequilibrium (LD)
analysis were investigated by using SNPStats (available online at
http://bioinfo.iconcologia.net/SNPstats). Logistic regression was performed to
investigate association between SNPs and LOAD. Generalized multifactor
dimensionality reduction (GMDR) was used to investigate the interaction among
gene- gene and gene- environment interaction. RESULTS: Logistic regression
analysis showed that LOAD risk was significantly higher in carriers of the A
allele of rs1784933 polymorphism than those with GG (GA+ AA versus GG), adjusted
OR (95%CI) = 1.63(1.27-1.98), and higher in carriers of G allele of the rs1805192
polymorphism than those with CC (CG+ GG versus CC), adjusted OR (95%CI) = 1.70
(1.25-2.27). GMDR analysis suggested a significant two-locus model (p = 0.0010)
involving rs1784933 and rs1805192, and a significant two-locus model (p = 0.0100)
involving rs1784933 and alcohol drinking. Haplotype containing the rs1784933- A
and rs689021- C alleles were associated with a statistically increased LOAD risk
(OR = 1.86, 95%CI = 1.37- 2.52, p < 0.001). CONCLUSIONS: We conclude that
rs1784933 and rs1805192 minor alleles, gene- gene interaction between rs1784933
and rs1805192, gene- environment interaction between rs1784933 and alcohol
drinking, and haplotype containing the rs1784933- A and rs689021- C alleles are
all associated with increased LOAD risk.
PMID- 28427150
TI - Senoptosis: non-lethal DNA cleavage as a route to deep senescence.
AB - DNA-damage-induced apoptosis and cellular senescence are perceived as two
distinct cell fates. We found that after ionizing radiation (IR)-induced DNA
damage the majority (up to 70 %) of senescent human diploid fibroblasts (HDFs)
were subjected to controlled cleavage of DNA, resulting in the establishment of a
viable and stable sub-G1 population, i.e. deeply senescent cells. We show that in
senescent HDFs this DNA cleavage is triggered by modest loss of the mitochondrial
membrane potential, which is not sufficient to activate caspases, but strong
enough to release mitochondrial endonuclease G (EndoG). We demonstrate that upon
gamma-irradiation in HDFs EndoG translocates into the nucleus playing an
essential role in the non-lethal cleavage of damaged DNA. Notably, the
established sub-G1 cell population does not contribute to the senescence
associated secretory phenotype (SASP), however, it exhibits increased senescence
associated beta-galactosidase activity. We show that EndoG knockdown causes an
increase in DNA damage, indicating a role of this enzyme in DNA repair. Thus, we
conclude that IR-induced deep senescence of HDFs exhibits features of both
senescence, such as cell cycle arrest and viability, and apoptosis like reduced
DNA content and no SASP, and, resembles uncomplete or stalled apoptosis, a
phenomenon we term senoptosis.
PMID- 28427151
TI - Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post
translational modifications.
AB - Vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily of
ligand-activated transcription factors. Activated VDR is responsible for
maintaining calcium and phosphate homeostasis, and is required for proper
cellular growth, cell differentiation and apoptosis. The expression of both
phases I and II drug-metabolizing enzymes is also regulated by VDR, therefore it
is clinically important.Post-translational modifications of NRs have been known
as an important mechanism modulating the activity of NRs and their ability to
drive the expression of target genes. The aim of this mini review is to summarize
the current knowledge about post-transcriptional and post-translational
modifications of VDR.
PMID- 28427153
TI - Comparison between proton boron fusion therapy (PBFT) and boron neutron capture
therapy (BNCT): a monte carlo study.
AB - The aim of this study is to compare between proton boron fusion therapy (PBFT)
and boron neutron capture therapy (BNCT) and to analyze dose escalation using a
Monte Carlo simulation. We simulated a proton beam passing through the water with
a boron uptake region (BUR) in MCNPX. To estimate the interaction between
neutrons/protons and borons by the alpha particle, the simulation yielded with a
variation of the center of the BUR location and proton energies. The variation
and influence about the alpha particle were observed from the percent depth dose
(PDD) and cross-plane dose profile of both the neutron and proton beams. The peak
value of the maximum dose level when the boron particle was accurately labeled at
the region was 192.4% among the energies. In all, we confirmed that prompt gamma
rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and
BNCT, respectively. We validated the dramatic effectiveness of the alpha
particle, especially in PBFT. The utility of PBFT was verified using the
simulation and it has a potential for application in radiotherapy.
PMID- 28427154
TI - MiR-signing gastrointestinal (con-)tract cancer.
PMID- 28427155
TI - Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab,
teprotumumab and figitumumab) effects on cancer therapy.
AB - BACKGROUND: Prognostic studies of insulin-like growth factor-1 receptor(IGF-1R)
inhibitors in cancer therapy had promising results in infratests, which exhibited
that IGF-1R signalling was crucial in cancer cells growth. However, the
conclusion of later clinical trials revealed a dim future for IGF-1R inhibitors
to treat cancer. We conducted this analysis to figure out how IGF-1R inhibitors
acted in clinical cancer therapy. MATERIAL AND METHODS: We searched up-to-date
studies about the single agent of IGF-1R inhibitors or combination with other
therapies in solid tumor. Five IGF-1R anti-agents were involved. The primary
endpoint was progression-free survival (PFS). The secondary endpoint was overall
survival (OS). RESULT: 17studies were enrolled. The results was not significant
in overall survival (I2=37.1%, P=0.080, HR=1.08, 95% CI=0.97-1.21) and in
progression-free survival (I2=0.0%, P=0.637, HR=1.05, 95% CI=0.98-1.12). OS for
dalotuzumab, breast cancer, colorectal cancer, and PFS for prostate cancer even
indicated harmful effects. CONCLUSION: So far, anti-IGF-1R mono-antibodies did
not make significant differences in solid tumor prognosis. On the contrary,
pessimistic effects were shown in the dalotuzumab, breast cancer, colorectal
cancer and prostate cancer subgroups. Further studies of IGF-1R anti-agents were
needed, but unwarranted in unselected patients by predictive biomarkers.
PMID- 28427156
TI - The effects of DLEU1 gene expression in Burkitt lymphoma (BL): potential
mechanism of chemoimmunotherapy resistance in BL.
AB - Following a multivariant analysis we demonstrated that children and adolescents
with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in
event free survival (EFS) despite identical short intensive multi-agent
chemotherapy. However, how this deletion in the 13q14.3 region is associated with
a significant decrease in EFS in children and adolescents with BL is largely
unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the
region of 13q14.3. Here, we report that DLEU1 expression is implicated in the
regulation of BL programmed cell death, cell proliferation, and expression of
apoptotic genes in transcription activator-like effector nuclease (TALEN)s
induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines. Furthermore, NSG
mice xenografted with DLEU1 knockdown BL cells had significantly shortened
survival (p < 0.05 and p < 0.005), whereas those xenografted with DLEU1
overexpressing BL cells had significantly improved survival (p < 0.05 and p <
0.0001), following treatment with rituximab and/or cyclophosphamide. These data
suggest that DLEU1 may in part function as a tumor suppressor gene and confer
chemoimmunotherapy resistance in children and adolescents with BL.
PMID- 28427157
TI - The anti-tumor efficacy of 3C23K, a glyco-engineered humanized anti-MISRII
antibody, in an ovarian cancer model is mainly mediated by engagement of immune
effector cells.
AB - Ovarian cancer is the leading cause of death in women with gynecological cancers
and despite recent advances, new and more efficient therapies are crucially
needed. Mullerian Inhibiting Substance type II Receptor (MISRII, also named
AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential
target for ovarian cancer immunotherapy. We previously developed and tested 12G4,
the first murine monoclonal antibody (MAb) against human MISRII. Here, we report
the humanization, affinity maturation and glyco-engineering steps of 12G4 to
generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor
activity. The epitopes of 3C23K and 12G4 were strictly identical and 3C23K
affinity for MISRII was enhanced by a factor of about 14 (KD = 5.5 * 10-11 M vs
7.9 * 10-10 M), while the use of the EMABling(r) platform allowed the production
of a low-fucosylated 3C23K antibody with a 30-fold KD improvement of its affinity
to FcgammaRIIIa. In COV434-MISRII tumor-bearing mice, 3C23K reduced tumor growth
more efficiently than 12G4 and its combination with carboplatin was more
efficient than each monotherapy with a mean tumor size of 500, 1100 and 100 mm3
at the end of treatment with 3C23K (10 mg/kg, Q3-4D12), carboplatin (60 mg/kg,
Q7D4) and 3C23K+carboplatin, respectively. Conversely, 3C23K-FcKO, a 3C23K form
without affinity for the FcgammaRIIIa receptor, did not display any anti-tumor
effect in vivo. These results strongly suggested that 3C23K mechanisms of action
are mainly Fc-related. In vitro, antibody-dependent cytotoxicity (ADCC) and
antibody-dependent cell phagocytosis (ADCP) were induced by 3C23K, as
demonstrated with human effector cells. Using human NK cells, 50% of the maximal
lysis was obtained with a 46-fold lower concentration of low-fucosylated 3C23K
(2.9 ng/ml) than of 3C23K expressed in CHO cells (133.35 ng/ml). As 3C23K induced
strong ADCC with human PBMC but almost none with murine PBMC, antibody-dependent
cell phagocytosis (ADCP) was then investigated. 3C23K-dependent (100 ng/ml) ADCP
was more active with murine than human macrophages (only 10% of living target
cells vs. about 25%). These in vitro results suggest that the reduced ADCC with
murine effectors could be partially balanced by ADCP activity in in vivo
experiments. Taken together, these preclinical data indicate that 3C23K is a new
promising therapeutic candidate for ovarian cancer immunotherapy and justify its
recent introduction in a phase I clinical trial.
PMID- 28427158
TI - The varied distribution and impact of RAS codon and other key DNA alterations
across the translocation cyclin D subgroups in multiple myeloma.
AB - We examined a set of 805 cases that underwent DNA sequencing using the
FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling.
Known and likely variant calls from the mutational data were analyzed for
significant associations with gene expression defined translocation cyclin D (TC)
molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied
across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid
(HRD) and t(11;14) myeloma while being rare in MMSET and MAF. In addition, the
presence of RAS-RAF mutations was inversely associated with NFkappaB pathway
activation in all subgroups excluding MAF. In the MMSET subgroup, cases with low
FGFR3 expression frequently had RAS-RAF mutations. Conditional inference tree
analysis determined that mutation and homozygous deletion of TP53, CDKN2C, and
RB1 were key prognostic factors associated with adverse outcome in a non-relapse
clinical setting. In conclusion, this study highlights the heterogeneity in the
distribution and clinical outcomes of RAS codon and other mutations in multiple
myeloma dependent upon primary molecular subgroup.
PMID- 28427159
TI - Genome-wide analysis of long noncoding RNA and mRNA co-expression profile in
intrahepatic cholangiocarcinoma tissue by RNA sequencing.
AB - Long noncoding RNAs (lncRNAs), which are pervasively transcribed in the genome,
are emerging in molecular biology as crucial regulators of cancer. RNA-seq data
were downloaded from GEO of NCBI and further analyzed to identify novel targets
in intrahepatic cholangiocarcinoma (iCCA).We investigated differences in lncRNA
and mRNA profiles between 7 pairs of iCCA and adjacent normal tissues. 230
lncRNAs were differentially expressed more than four-fold change in iCCA tissues.
Among these, 97 were upregulated and 133 downregulated relatively to normal
tissues. Moreover, 169 lncRNAs and 597 mRNAs formed the lncRNA-mRNA co-expression
network which consist 766 network nodes and 769 connection edges. Bioinformatics
analysis identified these dysregulated lncRNAs were associated with cholesterol
homeostasis, insoluble fraction and lipid binding activity and were enriched in
complement and coagulation cascades and PPAR signaling pathway. These results
uncovered the landscape of iCCA-associated lncRNAs and co-expression network,
providing insightful information about dysregulated lncRNAs in iCCA.
PMID- 28427165
TI - Prognostic significance of tumor-associated macrophages in breast cancer: a meta
analysis of the literature.
AB - PURPOSE: Tumor associated macrophages (TAMs) are important prognostic factors and
have been proved to be associated with the invasion and migration of various
cancer. However, the relationship between TAMs and breast cancer outcomes remains
unclear. EXPERIMENTAL DESIGN: Sixteen studies with a total of 4,541 breast cancer
patients were included in this meta-analysis. Correlation of TAMs with overall
survival (OS), disease-free survival(DFS), relapse-free survival (RFS), breast
cancer special survival (BCSS) and clinicopathological features were analyzed.
Survival data and clinicopathological value were integrated by analyzing hazard
ratio(HR) and odds ratio(OR) separately and using Fixed-effect or Random-effect
model according to heterogeneity. All statistical tests were two-sided. RESULTS:
OS and DFS were correlated with high density of TAMs with HR= 1.504(1.200,
1.884)/ 2.228(1.716, 2.892) respectively. And subgroup analysis of location and
biomarker in OS and DFS group showed prognosis was associated with TAMs
distribution and biomarker selection. Besides, TAMs high infiltration was
significantly related to age, size, histologic grade, ER/PR status, basal
phenotype and vascular invasion. CONCLUSION: High density of TAMs was associated
with poor survival rates of breast cancer. TAMs in stroma are associated with
worse outcome than that in nest and using CD68 as a biomarker for TAMs to
evaluate the risk is better than CD163 or CD206 alone. Moreover, high
infiltration of TAMs was significantly associated with negative hormone receptor
status and malignant phenotype. TAMs infiltration can serve as a novel prognostic
factor in breast cancer patients.
PMID- 28427166
TI - CD147 overexpression may serve as a promising diagnostic and prognostic marker
for gastric cancer: evidence from original research and literature.
AB - Gastric cancer (GC) is one of the most common malignancies worldwide. The
expression of CD147 protein is associated with GC. However, the clinical role of
CD147 in GC has not been investigated extensively. Hence, we focused on studying
the association between the expression of CD147 and clinicopathological features
of GC patients in this study. Firstly, sixteen publications (1752 cases and 391
controls) and one from our own original research (143 cases) were included in the
meta-analysis to obtain a more precise estimation of the diagnostic value of
CD147. The results showed that expression rate of CD147 in the GC group is higher
than that in control group. Moreover, gender, TNM stage, lymph node metastasis,
and depth of invasion are all associated with CD147. Further, sections of gastric
tissue from 143 cases underwent immunohistochemical staining for evaluation of
CD147 protein expression. Our retrospective analysis demonstrated CD147 protein
expression was significantly associated with clinical N stage, and tumor stage.
Meanwhile, it can also serve as an independent prognosis biomarker. In
conclusion, our results support the role of CD147 as a good indicator of
diagnosis and prognosis.
PMID- 28427168
TI - Association between BRCA1 P871L polymorphism and cancer risk: evidence from a
meta-analysis.
AB - Breast cancer 1 (BRCA1) gene makes great contributions to the repair of DNA. The
association between BRCA1 P871L polymorphism and cancer risk has been
investigated in a growing number of studies, but the conclusions are not
conclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of
24 studies with 13762 cases and 22388 controls. The pooled results indicated that
BRCA1 gene P871L variant decreased risk of overall cancer (homozygous model: odds
ratio (OR) = 0.89, 95%confidence interval (CI) = 0.79-1.00; recessive model: OR =
0.89, 95% CI = 0.80-0.99). The stratified analysis observed decreased risk
associated with BRCA1 P871L in subgroups among Asians and high score studies, but
not Caucasians or low score studies. In conclusion, despite several limitations,
this meta-analysis suggested that BRCA1 P871L genetic variation may be associated
with decreased susceptibility to cancer.
PMID- 28427169
TI - Therapeutic role of glutamine in management of radiation enteritis: a meta
analysis of 13 randomized controlled trials.
AB - OBJECTIVE: To systematically evaluate the clinical efficacy of glutamine in
treating radiation enteritis in cancer patients treated with radiotherapy.
METHODS: Electronic databases including Pubmed, Embase, the Cochrane library, and
CNKI were systematically searched, until April 2016. Randomized controlled trials
(RCT) of glutamine in the treatment of radiation enteritis in cancer patients
were searched, and RevMan 5.3 software was used for Meta-analysis. RESULTS: A
total of 13 RCTs were included, involving 979 patients. The results of meta
analysis showed that the total efficacy of glutamine was higher for patients with
radiation enteritis compared with that in control group, however, there was no
statistically significant difference(OR = 3.07, 95%CI: 0.79-11.96; P > 0.05). The
combined ORs for all 5 grades(from grade 0 to grade 4) of radiation enteritis in
patients receiving glutamine were 2.06, 1.35, 0.55, 0.62 and 0.59, respectively(P
> 0.05 for all). Glutamine also failed to significantly improve the symptoms of
radiation enteritis in terms of tenesmus, abdominal cramping and blood in bowel
movement(P > 0.05). CONCLUSIONS: Implementation of glutamine fails to improve the
severity and symptoms in patients with radiation enteritis.